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Indian Heart J 2003; 55: 305–309
Kothari et al. Chronic Constrictive Pericarditis
305
Editorial
Chronic Constrictive Pericarditis: Pending Issues
SS Kothari, Ambuj Roy, VK Bahl
Department of Cardiology, All India Institute of Medical Sciences, New Delhi
C
hronic constrictive pericarditis (CCP) is a well
characterized clinical entity.1–3 With advances in the
understanding of hemodynamics, Doppler echocardiography, and cardiac cross-sectional imaging, the diagnosis
of CCP has been straightforward. However, it often
masquerades as chronic liver disease, cardiomyopathy,
unexplained heart failure, etc. Furthermore, there is a
remarkable paucity of information regarding the
pathogenesis, and the optimal management of patients
with CCP. In this article, we provide a brief perspective on
the recent advances in CCP, and highlight the need for more
evidence-based data regarding a disease that is still common
in India.
Etiology
Identifying the etiology of CCP has been notoriously
difficult. The vast majority of patients with idiopathic CCP
are suspected to have had tuberculosis in the past. While
proven tubercular pericarditis may present with dense
fibrosis without any direct evidence of tuberculosis, such
fibrosis may follow other etiologies of CCP as well. The
reported prevalence of idiopathic CCP has varied from 24%
to 61% in Indian studies,4–6 depending on the criteria used
to diagnose tubercular CCP. Tuberculosis remains a
common cause of CCP in developing countries, with a
reported incidence of 38%–83%.4,7–9 The etiology of CCP
in the western world has now undergone a significant
change, with tuberculosis reported in only 0%–1% of cases
in some recent series.10,11 The leading identifiable causes of
CCP are following cardiac surgery and radiation therapy,
besides viral pericarditis. 10–12 The incidence of CCP
complicating cardiac surgery is between 0.025% and
0.15% of patients undergoing open heart surgery. 13
However, the lack of reports of post-surgical and postradiation CCP from India is remarkable. An informal
inquiry in the five major Indian medical college hospitals
did not yield cases of CCP following cardiac surgery. Possibly
such cases are being missed.
Correspondence: Professor VK Bahl, Department of Cardiology,
All India Institute of Medical Sciences, New Delhi 110029
e-mail: [email protected]
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305
Pathogenesis
The precise pathogenesis of CCP remains unknown, and is
scantily investigated. CCP may result from the progression
of an acute pericarditis from a dry stage through an effusive,
absorptive, and constrictive phase sequentially; or it may
result from a smouldering fibrosis with no previous history
of an acute pericarditis (as occurs in the majority of
patients). The factors responsible for the resolution of
inflammation or its progression to severe fibrosis remain
unknown. For example, in nearly half the patients with
tubercular pericardial effusion resolution occurs without
constriction, while the rest develop CCP despite adequate
and similar antitubercular therapy.14 The virtual absence
of CCP following rheumatic fever,15 and its low incidence
in tubercular pericarditis in HIV-positive patients are
noteworthy.16 Little research has been done to unravel the
inflammatory repertoire of the pericardial tissue.17 The role
of cytokines in tubercular pericardial effusion has been
investigated recently. It appears that tubercular pericarditis
is a hypersensitivity reaction to antigens such as
tuberculoproteins. The increased production of interferongamma, tumor necrosis factor-alpha, and interleukin-1 and
interleukin-2 in tubercular pericardial effusion suggest that
the inflammation is orchestrated by T-helper-1
lymphocytes.18 T-lymphocytes and activated macrophages
seem to play an important role in granuloma formation
and fibrosis.19 However, the exact mechanism has not been
elucidated. Similarly, the mechanisms of constriction in
postoperative patients, in patients with collagen vascular
disease, or those with the rare but interesting hereditary
disease mulibreynanism remain unexplored and
unexplained.
Mechanism of Fluid Retention
In general, patients with CCP retain more water and
sodium than patients with myocardial disease. The ascites
in CCP is out of proportion to edema, and also occurs
earlier than peripheral edema, a sequence opposite to that
seen with other causes of congestive heart failure (CHF).
The cause of this “ascites precox” has never been
satisfactorily explained. It could simply be a reflection of
very high right atrial pressures compared to other causes
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306 Kothari et al. Chronic Constrictive Pericarditis
of CHF. Increased venous pressures, hypoalbuminemia
resulting from protein-losing enteropathy, cardiac
cirrhosis, increased capillary permeability, and impedance
to lymph flow have been suggested but appear to be
inadequate explanations.
The mechanisms of fluid retention in CCP have been
explored in a systematic fashion in only one study.20 In 16
patients with untreated CCP, it was found that the
magnitude and mechanisms of sodium and water retention
differed somewhat from a similar congestion resulting from
decreased cardiac output due to myocardial failure. For a
comparable reduction in cardiac output, volume retention
was higher and vascular resistance was lower in patients
with CCP compared to those with myocardial disease.20 The
activation of the renin–angiotensin–aldosterone and
sympathetic systems were found to be similar in CCP and
other causes of CHF.20 The atrial natriuretic peptide (ANP)
levels in patients with CCP were five times higher than those
in normal controls, but were only one-third of those seen
in myocardial disease.20,21 The ANP levels in CCP are less
than what might be expected on the basis of right atrial
pressures alone. This may be primarily due to less distensible
atria caused by the constrictive process in CCP, as ANP
release is mediated by atrial stretch. The greater salt and
water retention in CCP could be due to smaller increase in
ANP levels. The ANP hypothesis has been suggested to
explain the lack of pulmonary edema in CCP and
tamponade despite very high central pressures.22 ANP is
shown to increase capillary hydraulic conductivity, and
enhance transcapillary fluid movement.22 To the best of our
knowledge, ANP in restricted cardiomyopathy (RCM) has
not been studied systematically.
Interestingly, other neurohumoral or autonomic effects
may also be important. In CCP, severe autonomic
dysfunction was reported in all segments of the autonomic
nervous system.23 In contrast, autonomic dysfunction was
much less in patients with RCM, and involved the
parasympathetic efferent pathway.24 Thus, mechanisms
other than ANP may also be operative.
Prevention of Constrictive Pericarditis
Nonsteroidal anti-inflammatory drugs, colchicines, and
steroids may reduce the chances of CCP by preventing
recurrence of pericarditis. However, the data on this aspect
are scanty and inconclusive. Limited information is
available regarding even the commonly occurring
tubercular pericarditis. The oft-quoted South African trial25
in 240 patients of tubercular pericarditis reported a
significant reduction in the need for repeat pericardiocentesis in patients randomized to receive steroids for 11
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Indian Heart J 2003; 55: 305–309
weeks. But steroids did not reduce the need for
pericardiectomy at 24 months. 25 The study has been
criticized as it did not include all-cause mortality, did not
analyze data on the basis of intention-to-treat, and excluded
patients not adhering to the protocol. A re-analysis of this
trial by Ntsekhe et al.26 also did not give definite answers.
In the other trial of steroids in patients with established
CCP, 2 of the 53 patients (4%) treated with prednisolone
and 7 of the 61 patients treated with a placebo (11%) died
from pericarditis, and 11 (21%) and 18 (30%), respectively,
required pericardiectomy. However, these differences were
not statistically significant.27
Corticosteroids could have an adverse impact on the
already compromised immune status of patients with HIV
and tubercular pericarditis. However, in a recent trial of
58 patients, steroids led to a significant reduction in allcause mortality in HIV-positive patients with tubercular
pericarditis on 18-month follow-up.16 Interestingly, a reanalysis of the trial data failed to show the benefit of
steroids.26 Thus, there is still a need for large, multicentric,
prospective controlled trials to accurately assess the benefit
of adjuvant steroids in tubercular pericarditis.
Role of pericardial drainage: Usually, large effusions
that are unresponsive to treatment, unexplained effusions
or effusions that last for longer than 3 months warrant
pericardiocentesis. Such pericardiocentesis is curative in
half the cases.1 Whether routine drainage of pericardial
effusion is helpful in preventing the occurrence of CCP has
rarely been investigated.25,28 Strang et al.25 randomized
patients with tubercular pericarditis to open drainage, or
no drainage, and followed them up for up to 24 months to
assess their outcome. Open pericardial drainage did not
decrease mortality or improve clinical outcome at followup. The routine drainage of pericardial fluid in tubercular
pericarditis does not seem to be useful, especially in areas
with a high prevalence. It may be useful in areas where
tuberculosis is an uncommon cause of pericarditis as it may
help to obtain pericardial fluid for examination. In a study
of 71 patients with large pericardial effusion (>2 cm on
echocardiography) of different etiologies, routine drainage
did not yield significant diagnostic information, and was
not useful in preventing the occurrence of cardiac
tamponade or CCP.28
The efficacy of pericardiocentesis in preventing CCP in
hemorrhagic effusion has not been tested specifically. In
purulent pericarditis, adequate drainage and fibrinolytic
agents seem to reduce the occurrence of CCP, but again
the data are limited.29 In one study of 6 children with
pyopericardium, instillation of intrapericardial
streptokinase at a dose of 10 000 to 15 000 U/kg twice
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Indian Heart J 2003; 55: 305–309
daily for a mean of 6 days led to the resolution of
pericarditis, and freedom from CCP on follow-up.29
Diagnosis of CCP
Hemodynamics: The hemodynamic criteria to diagnose
CCP, viz. elevated diastolic pressures, typical pressure
waveforms, and equilibration of pressure of all four
chambers in diastole, have been discussed widely, yet these
may not be diagnostic in individual cases. In one study, onefourth of the patients could not be identified by these criteria
of equalization of the right and left ventricular diastolic
pressures within 5 mmHg, pulmonary artery systolic
pressure less than 50 mmHg, and right ventricular enddiastolic pressure more than one-third of the right
ventricular systolic pressure.30 Evidence of dissociation of
intracardiac and intrathoracic pressures, and the presence
of ventricular interdependence (i.e. reciprocal respiratory
variation in right ventricular/left ventricular pressures)
have improved the accuracy. Ventricular interdependence
had 100% sensitivity and 95% specificity for distinguishing
CCP from RCM.31 However, in real-world situations several
patient-related or other factors complicate the
interpretation of laboratory data. The presence of localized
constriction, associated myocardial dysfunction, other
valve disease, obesity, obstructive airway disease, previous
infarction, and other co-morbidities may influence their
measurement. For example, a disproportionately elevated
pulmonary artery wedge pressure was seen in patients with
mitral valve disease,32 and even evidence of ventricular
interdependece was reportedly lacking in a patient with a
localized constriction.33
Doppler echocardiography: Doppler echocardiographic
parameters have been a very valuable addition to the
diagnosis of CCP, and in its differentiation from RCM. The
initial study that suggested a cut-off of 25% respiratory
variation in mitral valve inflow velocities was based on the
data from only 7 patients with CCP.34 Subsequently, a larger
study found that 12% of patients did not show diagnostic
changes in these echocardiographic parameters.35 Several
caveats need to be considered in individual cases. For
example, a very high preload may be one reason for the
absence of respiratory variation, 36 and a reduction in
preload may be required to bring out the typical pattern,
or fluid challenge may be required to diagnose patients with
occult CCP.37 In addition, irregular breathing, irregular
heart rate, and short diastolic periods resulting from
tachycardia may cause difficulty in the interpretation of
respiratory variation of Doppler velocities. The additional
use of tissue Doppler imaging (TDI) may further enhance
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Kothari et al. Chronic Constrictive Pericarditis 307
the diagnostic utility of echocardiography. Reduced mitral
annular velocity on TDI was reported in RCM, whereas
these parameters were normal in patients with CCP in the
initial reports.38,39
Cross-sectional imaging: The other commonly used
investigation for the diagnosis of CCP is cross-sectional
imaging with computerized tomography (CT) and magnetic
resonance imaging (MRI). The diagnostic hallmark of these
tests is the presence of pericardial thickening with or
without calcification. While a minimal amount of
pericardial calcification is better detected by CT scan, MRI
provides better soft tissue characterization.40 Pericardial
thickening of more than 3 mm is usually taken as
abnormal; the usual thickening of the pericardium being
1–2 mm. The actual thickness of the pericardium is 0.4–1
mm, and this discrepancy between MRI and pathological
measurement is most likely due to a combination of volume
averaging, chemical shift artifact, motion artifact, and the
inclusion of a small amount of pericardial fluid in MRI
measurements.40 Though commonly used, the data on the
diagnostic utility of CT/MRI in CCP are not robust. In one
small study of 29 patients, pericardial thickening on MRI
was found to be 88% sensitive and 100% specific for
detecting CCP.41
It is important to look for additional findings suggestive
of CCP, such as dilated inferior vena cava (IVC), enlarged
atria, tubular-shaped ventricles, ascites and pleural effusion
on CT/MRI images. Myocardial tagging has also been
suggested as a new method of mitral/tricuspid annular
movement. As normal ventricles contract, there is a
slippage between the myocardium and pericardium;
however, once pericardial adhesions develop, this slippage
is absent and the tag lines passing through the myocardium
and pericardium are not deformed during the cardiac
cycle.42 The presence of abnormal diastolic motion of the
septum on cine MRI may also be a useful finding to diagnose
CCP, and to distinguish it from RCM.43
Thus, no single test in isolation should be considered
diagnostic of CCP.
CCP with Normal Pericardial Thickness
It is well known that pericardial thickening may be present
without CCP; however, it is not as well recognized that CCP
may occur with normal thickness of the pericardium,
which was reported in 18% of 143 patients in a recently
published series from the Mayo Clinic. These patients most
commonly had post-surgical and post-radiation CCP.12
Their clinical characteristics were similar to patients with
CCP with a thickened pericardium, and pericardiectomy
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308 Kothari et al. Chronic Constrictive Pericarditis
was very effective in relieving the symptoms. Microscopy
of the excised pericardium was abnormal in all the patients,
and included the presence of focal fibrosis, focal calcification
or inflammation. Thus, pericardiectomy should not be
denied to patients with typical clinical and hemodynamic
features of CCP but with a normal pericardial thickness on
imaging.
Transient CCP
It is conceivable that occasionally, the inflammatory
exudates causing clinical CCP may resolve with no features
of constriction on follow-up.44,45 Such an event occurred
in 15% of patients with tubercular pericarditis in one report
from South Korea.46 The resolution occurred within 2
months in the majority of patients. Perhaps transient CCP
could occur even more often with purulent pericarditis.
However, decisions regarding the management of these
patients should be based on the overall clinical profile.
Surgical Aspects
Pericardiectomy is the definitive treatment for CCP but its
timing, surgical approach, and preoperative stabilization
need careful consideration. Various approaches to
pericardiectomy, i.e. median sternotomy, lateral
thoracotomy and bilateral thoracotomy with or without
the use of cardiopulmonary bypass, and anterior or total
removal of the pericardium have been described depending
on patient population or personal preferences. The surgical
mortality of pericardiectomy continues to be high, and has
been generally reported to be 6%–12%4,10,47.A subgroup of
patients with calcific CCP had a mortality of 19% in a recent
series. 48 The negative predictors of survival after
pericardiectomy include NYHA class IV, low-voltage ECG
complex, markedly increased atrial pressure, associated
organ failure, and post-radiation CCP.10,46,47,49
The optimal timing of pericardiectomy is important.
Pericardiectomy is unwarranted too early or too late in the
course of the disease.1 Long-standing CCP may lead to
myocardial atrophy. Medical therapy may be better in some
patients with CCP having adverse risk factors in whom the
surgical mortality approaches 30%–40%.1 In purulent
pericarditis, it is important not to intervene in the subacute
stage when a plane of cleavage has not developed clearly.50
The occurrence of low cardiac output following CCP is often
a reflection of the chronicity of CCP and associated
myocardial atrophy. Acute cardiac dilatation and failure
following pericardiectomy may occur unpredictably,51 and
is not well characterized. Preoperative inotropes for 48
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Indian Heart J 2003; 55: 305–309
hours,47 and preoperative digitalization are often used to
reduce the chances of postoperative heart failure but their
effectiveness is not clear. The improvement following
pericardiectomy may be rapid but, at times, occurs over a
few weeks.1 However, residual CCP or recurrence of CCP
due to epicardial constriction remains a persistent problem.
Multiple incisions into the fibrous epicardium while
protecting the myocardium and coronary arteries are useful
in relieving the constriction (waffle procedure).52 In patients
with extensive calcific plaques, where large plaques do not
permit the development of cleavage planes, wedge incisions
that reach up to the epicardium help release constriction.47
More recently, ultrasonic decalcification has been used in
tough calcific lesions.48
Conclusion
CCP continues to intrigue and engage clinicians despite
advances in knowledge about the disease. No single test or
diagnostic finding should be considered pathognomic of
CCP. A combination of clinical and investigative results
should be thoughtfully analyzed to prevent misdiagnosis.
Further research is required to understand the
pathogenesis, prevention, and optimal treatment of CCP.
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310 Enas
et al. Prudent Diet and Preventive Nutrition
Review
Article
Indian Heart J 2003; 55: 310–338
Prudent Diet and Preventive Nutrition From Pediatrics
to Geriatrics: Current Knowledge and Practical
Recommendations
Enas A Enas, A Senthilkumar, Hancy Chennikkara, Marc A Bjurlin
Coronary Artery Disease in Asian Indians (CADI) Research Foundation, and University of Illinois, Chicago, USA
“A
man is what he eats” (German proverb). Food
provides not only the essential nutrients for life but
also other bioactive compounds for the promotion of health
and the prevention of disease.1–3 The results of 50 years of
intensive worldwide research support the conclusion that
diet is the major environmental cause of atherosclerosis
and cardiovascular diseases (CVD), especially in genetically
susceptible individuals.4 A high-caloric diet, combined with
limited physical activity, contributes to dyslipidemia, insulin
resistance, diabetes, and obesity. All these abnormalities
increase the risk of CVD. Over the past few decades, the
prevalence of obesity has doubled in adults, and quadrupled
in teenagers in the USA. A similar pattern is emerging in
India, where an epidemic of coronary artery disease (CAD)
and diabetes is under way, with no signs of a downturn.
Whereas the rates of CAD have declined by 60% in the US,
the rates have increased by 300% in India over the past 30
years.5 The public and physicians are constantly bombarded
with confusing and conflicting dietary advice. This review
analyzes the important recent developments in the fields
of diet and nutrition for the prevention and treatment of
CVD and diabetes, with particular attention to Asian
Indians.
Facts and Myths about Cholesterol, Fats, and Meats
The modern understanding of the role of nutrition in heart
disease began in 1903 when Anitschkow and Chalatow
found that a diet of meat, milk, and egg produced
atherosclerosis in rabbits. A decade later, serum total
cholesterol (TC) level was found to be the agent responsible.
Contrary to common belief, the contribution of dietary
cholesterol to serum TC is small (<10 mg/dl). The average
adult on a western diet consumes about 300 mg of
cholesterol daily, which is about the size of 3 toothpicks,
and hardly 3 cal. Nonetheless, high intakes of dietary
cholesterol increase the number of circulating low-density
Correspondence: Dr Enas A Enas, CADI Research Foundation, 1935, Green
Trails, Lisle IL, 60523 USA. e-mail: [email protected]
IHJ-584-03.p65
310
lipoprotein (LDL) particles.6 Dietary cholesterol is found
only in the animal kingdom; 3 oz of beef, lamb, or pork
contains 75 mg of cholesterol. Most of the cholesterol in
poultry is in the skin, and some in dark meat. One cup of
milk has 33 mg, 2 egg yolks have 560 mg, and 100 g of
brain has 2000 mg of cholesterol. One hundred grams of
shrimp contain about 150 mg of cholesterol but <1 g of
saturated fat. The recommended dietary intake of
cholesterol and various types of fat is given in Table 1.1,6–12
The contribution of dietary saturated fat to serum TC is
very large—10 times greater than that of dietary
cholesterol. Fats are substances consisting of a combination
of fatty acids, which are classified as saturated (SAFA),
monounsaturated (MUFA), polyunsaturated (PUFA), and
transunsaturated (TRAFA), depending on the location and
number of double bonds.13 It is not often appreciated that
the quality of the fat is more important than the quantity
of fat consumed. The National Cholesterol Education
Program (NCEP) recommends an intake of total fat of 25%–
35%, MUFA up to 20%, PUFA up to 10%, and SAFA <7%
of the total energy14 (Table 1). Although many affluent
Asian Indians consume 50% of energy from fat, the average
consumption is about half this amount (20%–25% of the
energy). Increasing the MUFA intake to 20%, and total fat
intake to 35% of the energy appears to be appropriate for
Asian Indians because of the beneficial effects on highdensity lipoprotein (HDL) and triglycerides (TG) . The NCEP
dietary guidelines for PUFA and SAFA seem appropriate for
Asian Indians without any modification.
Saturated fatty acids, the arch villain of
atherosclerosis: Excessive consumption of SAFA is the
principal dietary culprit contributing to elevated serum
TC level, which is the primary determinant of
atherosclerosis.15,16 Differences in CAD mortality worldwide
are explained by differences in SAFA intake and the
resulting serum TC levels in 40 countries, except for France,
Finland, and India.16–18 Intake of SAFA suppresses the LDLreceptor activity and decreases the clearance of LDL from
the circulation, resulting in a marked elevation of its level.19
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Enas et al. Prudent Diet and Preventive Nutrition 311
Table 1. Recommended daily energy intake and major sources of dietary fats1,6–12
Recommended
intake
Current
intake
(USA)
Major sources
Total fat
30%–35%
(40–75 g)
34%
Dairy products and animal flesh are the major sources of dietary fat; the
former contribute more than the latter.
Cholesterol
<200 mg
270 mg
Egg yolk, brain, organ meat, beef, lamb, pork, poultry (thigh and skin), shell
fish, shrimp, prawn, full-fat milk (especially buffalo milk), high-fat dairy
products (cream, ice cream, milk shake, cheese, curd)
SAFA
<7%
(10–15 g)
12%
Beef, lamb, pork, bacon, sausage, ribs, poultry with skin, butter, ghee,
vanaspathi (vegetable ghee), desserts, bakery products (cakes, biscuits,
cookies, donut), cheese, ice cream, full-fat milk, tropical oils (coconut, palm
kernel, and palm oils)
TRAFA
Avoid
<2%
Hard margarine, vegetable shortening, frying fats (especially those used
repeatedly), bakery products (cakes, Danish pastry, donuts, crackers, rusk,
biscuits, cookies, white bread), French fries, fried chicken, peanut butter,
nondairy creamer, tortillas, pizza, and virtually all “crispy and crunchy
foods”
MUFA
Up to 20%
14%
Olive oil, canola oil, mustard oil, peanut oil, macadamia nuts, hazelnuts,
pecans, peanuts, almonds, cashew nuts, pistachio nuts, avocado, dairy
products, beef, lamb, mutton, poultry
n-6 PUFA
7%–8 %
6%–8%
Vegetable oils (soybean, corn, safflower, sunflower, and cottonseed)
n-3 PUFA
2%–3%
<1%
Fatty fish (mackerel, halibut, lake trout, herring, sardines, albacore tuna,
salmon), meat, poultry, vegetables (tofu, soybeans, pinto beans, flax seeds),
vegetable oils (soybean, canola), salad dressing, whole grains, and DHAenriched egg, nuts (walnuts, butternut, flax seeds, pecans)
SAFA raises the serum TC level thrice as much as PUFA,
and MUFA lowers it. For example, substitution of 20% of
the daily energy intake of carbohydrate by SAFA increases
the TC level by 30 mg/dl, whereas PUFA and MUFA lower it
by 10 mg/dl.13 Most of this increase is due to an increase in
LDL. Although some increase in HDL also occurs, it is not
sufficient to offset the atherogenicity and thrombogenicity
resulting from marked elevation of LDL.6,20
Our diet contains SAFA of different chain lengths with
varying atherogenic properties. According to their chain
lengths, SAFA can be classified as short chain (4:0–6:0),
medium chain (8:0–10:0), long chain (12:0–18:0), and
very long chain (20:0–24:0) fatty acids. Stearic acid
(C18:0) is desaturated to oleic acid soon after its absorption,
and hence does not raise the TC level.21,22 Therefore, its use
need not be restricted and, in fact, it can be recommended.23
SAFA with chain lengths of 12–16 have the most
cholesterol-raising properties. 24 These are lauric acid
(C12:0), myristic acid (C14:0), and palmitic acid (C16:0).
These 3 fatty acids account for only 25%–30% of the total
dietary fat but 60%–70% of SAFAs in western diets.24
IHJ-584-03.p65
311
Palmitic acid is the most common fatty acid in the human
diet, and the principal SAFA in both animal fats and palm
oil. In a study conducted in a metabolic ward, 40% of
energy as palmitic acid raised the TC by 25 mg/dl v. 15 mg/
dl with lauric acid.21 Myristic acid is the most powerful
cholesterol-raising SAFA, and increases the TC level 50%
more than palmitic acid. Replacement of 20% of energy
from carbohydrate with myristic acid raises the blood TC
level by 46 mg/dl, compared to 30 mg/dl with palmitic acid,
and 20 mg/dl with lauric acid.25 Most of the rise in the TC
level is due to an increase in LDL, the respective contribution
from HDL being 16 mg/dl, 8 mg/d and 12 mg/dl.25 The
major sources of myristic acid are butter and tropical oils
(Table 2).6,20–25 The TC-raising potential of lauric acid is 33%
less than that of palmitic acid, and it is the principal SAFA
in coconut and palm kernel oils, both containing 48%.23–25
Coconut and palm oils are also high in myristic acid (18%),
and this explains why the consumption of these oils raises
the LDL level in a fashion similar to that of butter
(Fig. 1).25,26 Studies in laboratory animals indicate that
coconut oil increases both TG and LDL levels;6,27,28 the claim
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312 Enas et al. Prudent Diet and Preventive Nutrition
Table 2. Chemical characteristics and atherogenicity of major fatty acids6, 20–25
Fatty acids
Chemical
structure
Atherogenicity
Comments
Highly atherogenic and thrombogenic. Markedly increases LDL level.
Slightly increases HDL level.
SAFA
Lauric acid
C12:0
⇑
Coconut oil 48%, palm oil 48%, and butter fat 3%.
Myristic acid
C14:0
⇑⇑⇑
Palmitic acid
C16:0
⇑⇑
Most potent cholesterol-raising SAFA. Coconut 18%, palm kernel oil
18%, butter fat 18%, animal fats 1%–5%
Most common and reference standard of SAFA. Palm oil 45%,
butter fat 26%, beef fat 26%, mutton fat 24%, chicken fat 23%,
pork fat 25%, cocoa butter 26%, coconut oil 9%, and palm kernel
oil 8%.
Stearic acid
C18:0
⇔
TRAFA
Elaidic acid
C18:1 n-9 trans
⇑⇑⇑
C18:1 n-9
⇓⇓
C18:2 n-6
Butter fat 28%, beef fat 39%, mutton fat 33%, chicken fat 42%,
pork fat 45%, cocoa butter 35%, coconut oil 7%, palm kernel oil
14%, and palm oil 39%.
Lowers LDL levels.
Lowers HDL level to a small extent
Antiatherogenic.
n-6 PUFA
Linoleic acid
Increases Lp(a), TG, small, dense LDL levels. Decreases HDL level; 3fold increase in cardiac arrest.
Fried food, crispy food, cakes, biscuits, donuts, pizza, reused frying
oils.
Significantly lowers LDL level.
Raises HDL level.
Lowers insulin resistance.
Antiatherogenic and antithrombogenic.
MUFA
Oleic acid
Raises HDL level without raising LDL level. Butter fat 13%, beef fat
22%, mutton fat 25%, chicken fat 6%, pork fat 12%, cocoa butter
35%, coconut oil 3%, and palm oil 4%.
⇓⇓
Predominant PUFA in western diets.
Decreases LDL, and TG levels, blood pressure, and risk of sudden
death.
Increase HDL level, heart rate variability.
Antiarrhythmic and antithrombogenic effects
n-3 PUFA
Alpha-linolenic acid
(ALNA)
C18:3 n-3
⇔
Precursor to EPA and DHA.
Flaxseed oil 50%, canola oil 10%, mustard oil 10%
Eicosapentaenoic acid
(EPA)
C20:5 n-3
⇔
Fatty fish (sardines, mackerel, salmon)
Docosahexaenoic acid
(DHA)
C22:6 n-3
⇔
Fatty fish (sardines, mackerel, salmon)
that lauric acid does not raise TC is not supported by scientific
data.21,23 Recent studies have shown that caprylic acid (C:8)
and capric acid (C:10) raise the LDL level to about 50% that
of palmitic acid, and raise the TG level.6,23–25 Coconut oil
contains 14% of these two cholesterol-raising SAFA.
Replacing 5% of the daily energy intake of SAFA with
MUFA and PUFA could reduce the risk of CAD by 42%.29
Therefore, substituting MUFA and PUFA for SAFA and
TRAFA is more effective in lowering the risk of CAD than
IHJ-584-03.p65
312
simply reducing the total amount of fat.30 Since 1970, the
total fat intake decreased from 42% to 34%, and SAFA from
18% to 12% in the USA, as a result of nationwide changes
in dietary habits.2,31 This change in dietary fat intake is
primarily responsible for the decrease in serum TC level from
220 to 200 mg/dl in the US population. This decrease in
TC level is principally responsible for the dramatic reduction
in CAD, during a period when the rates of obesity and
diabetes doubled in Americans.32
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Fig. 1. Predicted change in HDL and LDL when all fat in Dutch diet is replaced
by a particular oil.
Transfatty acids (TRAFA)—the hardened fat that
hardens arteries fast: TRAFA is formed during the partial
hydrogenation of vegetable oils, a process that converts oils
into solid or semisolid fats for subsequent use in food
products. This process not only improves the texture and
firmness but also markedly increases the shelf-life of food
by minimizing oxidative spoilage.33 Elaidic acid (n-9 trans
18:1) is the principal TRAFA, although several other trans
isomers are also formed.23 Such oils are used in commercial
baked goods, and for cooking in most fast-food chains in
western countries.34 Perhaps an equally important and
often neglected cause of TRAFA formation is the
spontaneous hydrogenation of vegetable oils during deepfrying.35 Very small amounts of TRAFA are also found in
beef and dairy products (Table 1).
Consumption of TRAFA has a greater adverse effect on
lipoproteins than that of SAFA.36 Whereas both SAFA and
TRAFA increase LDL levels considerably, TRAFA also
decreases HDL levels, thereby increasing the TC/HDL ratio,
the single best lipid-related risk factor for CAD.37 Replacing
9% of calories from SAFA with TRAFA results in a 20%
decrease in HDL level.38 Other important adverse effects of
TRAFA consumption include increases in lipoprotein(a)
(Lp[a]), TG, and small, dense LDL levels,34,38–44 as well as
increased platelet aggregation, endothelial dysfunction,
and sudden death.34 TRAFA are stronger predictors of CAD
and diabetes than SAFA and carbohydrates.1,45–47 In the
Nurses’ Health Study, women in the highest versus the
lowest quartile of TRAFA consumption had a 50% higher
risk of CAD.48 It is estimated that a substitution of 2% of
calories from TRAFA with MUFA and PUFA results in a 53%
reduction in CAD risk—a risk double that of substitution
of calories from SAFA.29 TRAFA consumption also markedly
increases the postprandial insulin response in diabetic
patients.49 Replacing 2% of energy from TRAFA with PUFA
IHJ-584-03.p65
313
Enas et al. Prudent Diet and Preventive Nutrition 313
would lead to a 40% reduction in diabetes.45 SAFA calories
should not be replaced by TRAFA calories; doing so is like
jumping from the frying pan to the deep-fat fryer.50
The average consumption of TRAFA in the USA and
Europe is low (<2% of energy or 11–27 g/day). 51,52
However, TRAFA accounts for about 5% of fat in American
diets, and 5% of fat stored in adipose tissue.33,50,53 Butter
contains 60% SAFA, whereas stick margarine contains
16% TRAFA. The tub or soft margarine contains only 2 g
of TRAFA per 15 ml. Therefore, the fat-spread of choice
remains soft margarine;54 olive oil may be an even better
substitute. Although many margarines and shortenings
previously contained up to 50% of TRAFA, in most western
countries, these products currently have a low TRAFA
content due to recent manufacturing changes.47 However,
frying fats used in fast-food outlets still contain over 30%
of TRAFA. French fries sold in these outlets provide 7–8 g
of TRAFA per portion. About one-third of TRAFA in the
western diet comes from French fries, fried chicken, pizza,
and cookies.
The TRAFA consumption is likely to be high in Asian
Indians because deep-frying is a favorite mode of cooking
at home as well as in restaurants. Deep-frying is associated
with spontaneous hydrogenation and TRAFA formation,
and repeated re-use of oils previously used for deep-frying
may further increase the TRAFA content. These practices
appear to be the norm rather than the exception, and may
be of enormous public health importance, especially with
regard to elevated Lp(a) levels, and high rates of CAD in
this population. There is an urgent need to ascertain and
disseminate the TRAFA content of vanaspathi (vegetable
ghee) and frying oils used in India. As of today, we are not
aware of any industrial manufacturing changes aimed at
lowering the TRAFA content of Indian foods, as has been
done in western countries.
MUFA, the good fat that raises the good cholesterol:
Diets high in MUFA (oleic acid C18:1) make LDL resistant
to oxidation, restore LDL-receptor activity, and markedly
lower LDL levels. Substitution of 20% of energy from
carbohydrates with MUFA decreases TC by 10 mg/dl. The
reduction in TC is 3-fold higher when MUFA replaces SAFA.
For example, TC decreases by 40 mg/dl when 20% of energy
from SAFA is replaced with MUFA.13, 25 The effect on small,
dense LDL is even greater. Other beneficial effects of MUFA
include the favorable influence on blood pressure,
endothelial activation, inflammation, and thrombogenesis.
A higher intake of MUFA lowers insulin resistance
and diabetes, unlike SAFA and TRAFA, which increase
it. 45,49,55–60 Consumption of MUFA offers the unique
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314 Enas et al. Prudent Diet and Preventive Nutrition
advantage of effectively lowering LDL levels without
lowering HDL or raising TG levels. Individuals with low HDL
levels have a high risk of CAD.61,62 Subjects with high TG,
especially those with the metabolic syndrome and diabetes,
are highly sensitive to the TG-raising effects of a high
carbohydrate load. A high carbohydrate diet is associated
with highly atherogenic, small, dense LDL particles, while
high-fat diets are associated with less atherogenic, buoyant
LDL particles. Thus, replacing SAFA with MUFA is more
effective in preventing CAD than reducing the total fat
intake, especially in Asian Indians, a population with high
rates of prevalence of the metabolic syndrome and diabetes.
The NCEP III has recommended up to 20% of total calories
from MUFA (Table 1). This recommendation seems
particularly appropriate for Asian Indians.32
In Mediterranean countries, the high intake of MUFA
in the form of olive oil is inversely related to CAD.15 The
Nurses’ Health Study and other studies of almost 300 000
Americans showed that a diet rich in MUFA in the form of
canola oil also reduces the risk of CAD.29,63,64 Contrary to
common belief, energy-controlled, high-MUFA diets do not
promote weight gain, and are more acceptable than lowfat diets for weight loss in obese subjects. The addition of
MUFA should be at the expense of SAFA and carbohydrates.
Since all fats are high in calories (9 cal/g), failure to decrease
the energy from carbohydrates and SAFA would invariably
result in weight gain, and mitigate most of the beneficial
effects of MUFA.
Meat and dairy products, which are also rich in SAFA,
provide most of the MUFA in western diets. Olive oil and
canola oil are good sources of MUFA (Table 3),65 canola oil
appears to be even better as it contains less SAFA and more
PUFA, especially alpha-linolenic acid (ALNA). Mustard oil
is high in MUFA but also high in erucic acid, which is known
to have toxic effects on the heart. Canola oil is genetically
engineered mustard oil without erucic acid. Nuts and
avocado are excellent sources of MUFA and are
recommended, provided the quantity is no more than 50–
100 g/day.66 Groundnut (peanut) products are a rich source
of MUFA; they are inexpensive and widely available in
India.67
PUFA, another healthy substitute for SAFA: There are
2 series of PUFA that are deemed essential. Linoleic acid
(C18:2 n-6) is the predominant omega-6 or n-6 PUFA. The
predominant (parent) omega-3 or n-3 PUFA is linolenic acid
(18:3 n-3).23 Linoleic acid increases the fecal excretion of
steroids, and inhibits the hepatic synthesis of apo Bcontaining lipoproteins. Replacing SAFA with PUFA
reverses the suppression of LDL-receptor activity by
cholesterol-raising SAFA (similar to that of MUFA).6,68
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Table 3. MUFA, PUFA, and SAFA content (%) in 100 g of
various cooking oils65
MUFA PUFA SAFA
Sunflower oil, high oleic (>70%)
Safflower oil, high oleic (>70%)
Olive oil
Almond oil
Mustard oil
Canola oil
Cod liver oil
Peanut oil
Sunflower oil, linoleic (<60%)
Sesame oil
Rice bran oil
Palm oil
Cocoa butter
Corn oil
Soybean oil
Walnut oil
Sunflower oil, linoleic (>60%)
Cottonseed oil
Safflower oil, linoleic (>70%)
Palm kernel oil
Coconut oil
84
75
74
70
59
59
47
46
45
40
39
37
33
24
23
23
20
18
14
11
6
4
14
8
17
21
30
23
32
40
42
35
9
3
59
58
63
66
52
75
2
2
10
6
14
8
12
7
23
17
10
14
20
49
60
13
14
9
10
26
6
82
92
Substituting 20% of energy from SAFA with PUFA
decreases the TC level by 40 mg/dl. Most of the reduction
is in LDL, and the number of apo B particles.23,25 PUFA does
not raise the TG level, and sometimes lowers it.69 The two
undesirable effects of PUFA are increased susceptibility for
peroxidation, and lowering of the HDL level.10,70–72 HDL
levels are reduced by about 1% for every 2% of MUFA or
SAFA energy substituted with PUFA.6,70–72
The substitution of PUFA for SAFA calories has played a
major role in reducing TC levels and CAD in the USA. The
CAD mortality rate declined by 60% in the past 3 decades
in the USA.73 About a third of the decline in CAD rates is
attributed to a 6%–8% decrease in the serum TC level in
the population; this, in turn, was due to an increase in the
consumption of PUFA from 3% to 6%, and a decrease in
SAFA consumption from 16% to 12% of the energy. The
importance of PUFA is further underscored by the marked
differences in PUFA consumption, which parallel the 4-fold
difference in CAD rates between France and Finland.16
Vegetable oils, such as soybean, corn, safflower, sunflower,
and cottonseed, are the primary sources of n-6 PUFA
(Table 1). Their average consumption in the western diet is
6%–8% of energy, (17 g/day for men, and 12 g/day for
women).74
Contrary to previous fears, n-6 PUFA do not antagonize
the anti-inflammatory effects of n-3 PUFA nor do they raise
the risks of breast, colorectal, or prostate cancer in
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Indian Heart J 2003; 55: 310–338
humans.75,76 However, a very high n-6 PUFA to n-3 PUFA
ratio may increase the thrombogenicity through increased
production of arachidonic acid and thromboxane A2. This
is because linoleic and linolenic acids use the same set of
enzymes for desaturation and chain elongation.77 An n-6
PUFA to n-3 PUFA ratio of 3:1 appears to be optimum.78–80
Japan, which has one of the highest rates of fish
consumption, has recently changed the recommendation
of this ratio from 4:1 to 2:1;81 this ratio may be advisable
for vegetarians).9
Fish, a tasty way to prevent sudden death: Fish do not
die from myocardial infarction (MI), and populations that
consume large amounts of marine foods have a low
prevalence of CVD death.82–99 Replacing high-fat meat with
fish is also associated with a decreased risk of CAD. The
results of several large studies show that one or two fish
meals per week are associated with a 30%–50% reduction
in sudden death.84,95,98 In a meta-analysis of 11 prospective
studies involving 116 764 individuals, fish consumption
was inversely related to CAD death. This report suggests
that 40–60 g/day of fish consumption is optimal, and
results in a 40%–60% risk reduction.100 Greater intake has
no additional benefits, and suggests a threshold effect.101,102
However, a recent large study of 5103 women with diabetes
showed a dose–response relationship. Consumption of fish
1–3 times per month was associated with a 40% risk
reduction, and a 64% risk reduction was seen among those
who consumed fish >5 times per week.102,103 The benefit is
seen in people with and without prior heart disease.104
These benefits persist as long as the fish consumption is
continued.
Fish is a tasty food that contains many essential
nutrients, such as selenium, iodine, vitamin D, and n-3
PUFA.97,105 The beneficial effects of fish are largely mediated
through n-3 PUFA, which displace arachidonic acid from
platelet phospholipid stores, thereby reducing the available
substrate for thromboxane A2 synthesis.106,107 The principal
effects of n-3 PUFA are antithrombogenic and
antiarrhythmic, whereas that of n-6 PUFA is
antiatherogenic.108–117 The serum levels of n-3 PUFA are
inversely related to sudden death.66,82,89,93,95,118–121 The
consumption of n-3 PUFA decreases blood pressure, and
homocysteine level, increases HDL level, and improves
hemostatic factors (Table 4). 10,75,122–132 A 30%–50%
reduction in TG can be achieved by taking 3–5 g/day of n3 PUFA.130
The major n-3 PUFA in fish oils are eicosapentaenoic
acid (EPA) (20:5 n-3) and docosahexaenoic acid (DHA)
(22:6 n-3); together they constitute 26% of fish oil fatty
acids.23 The benefits from n-3 PUFA are greater with DHA
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Enas et al. Prudent Diet and Preventive Nutrition 315
Table 4. Omega-3 fatty acids and CVD10,75,122–132
• Decrease the risk of ventricular fibrillation and sudden death
Increase cell membrane PUFA
Favorably alter cardiac ion channel function and action
potential
Decrease the ventricular fibrillation threshold
Increase heart rate variability
• Decrease the risk of stroke and MI
• Decrease platelet reactivity, aggregability, and the risk of
thrombosis
• Reduce monocyte reactivity
• Reduce inflammatory cytokines and response
• Improve endothelial function
• Reduce the expression of vascular adhesion molecules
• Markedly lower the TG and remnant lipoprotein levels
• Decrease the growth of atherosclerotic plaques
• Decrease homocysteine levels
• Improve insulin sensitivity and reduce the risk of diabetes
• Slightly lower blood pressure
and EPA found in fatty fish, shellfish, and marine mammals
than with ALNA found in canola oil, soybean oil, and
walnut.108 It is important to distinguish between lean and
fatty fish for cardioprotection, because the content of n-3
PUFA is highest in fatty fish.119 Fatty fish, such as mackerel,
sardine, and salmon, are widely available and inexpensive.
Heating is associated with significant loss of n-3 PUFA.9
Frying fish is associated with an even greater loss of EPA
and DHA, and may be particularly harmful if fried in
SAFA.133 The current intake of DHA and EPA is only 200
mg/day, and needs to be increased 5-fold to meet the dietary
goals.11
Both plant-based (ALNA), and fish-based (EPA and DHA)
supplements have shown benefits in secondary
prevention.89,90,134,135 In one such trial of 605 French men
recovering from an MI, there was a 70% reduction in total
and cardiac death during a follow-up of 27 months in those
who received an experimental “Mediterranean diet” using
canola oil-based margarine, enriched with n-3 PUFA.136 In
another large randomized study of 11 324 survivors of a
recent MI, there was a 20% reduction in total deaths, 30%
reduction in CVD deaths, and 45% reduction in sudden
deaths among those who received n-3 PUFA 1g/day.90 The
totality of the data suggest that n-3 PUFA can be considered
as the best antiarrhythmic agent and antifibrillatory
treatment. 106,117,133,135 Cardiologists and their patients
should pay serious attention to this new paradigm in the
diet–heart hypothesis, and increase the intake of fish and
fish oil.133,137
The amount of n-3 PUFA necessary for cardioprotection
is surprisingly low. The current recommendation is to take
2–3 fish meals per week (200–300 g/week of fish). A less
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316 Enas et al. Prudent Diet and Preventive Nutrition
attractive alternative is to consume 1000 mg/day of n-3
PUFA (contained in 3000 mg of fish oil capsules).10,11,74,96,133
The current intake of n-3 PUFA in the US is 1600 mg/day
or 0.7% of the calories, which is about half the
recommendation.11 Fish is more beneficial than fish oil, but
the latter may be required in most patients with CAD to
obtain the required amount of n-3 PUFA.90 Patients with
CAD should consume about 1800 mg/day of n-3 PUFA
(DHA and EPA) as the best insurance against sudden death.
Alpha-Linoleic acid (ALNA)—the n-3 PUFA of the
plant kingdom: There is no DHA and EHA in a vegetarian
diet. Vegetarians derive their n-3 PUFA almost exclusively
from ALNA, which is also the major type of n-3 PUFA in
omnivores. 138 There is increasing evidence for the
cardioprotective effects of ALNA, albeit less than EPA and
DHA.139 In a large study involving 43 700 men, increased
intake of ALNA reduced the risk of MI by 60%.64 A similar
risk reduction was also observed in the Nurses’ Health
Study and Multiple Risk Factor Intervention Trial
(MRFIT). 93,140 Some vegetable oils are high in ALNA
(flaxseed oil 50%, canola oil 10%, mustard oil 10%, soybean
oil 7%) while others are low (groundnut oil <0.5%).141
Walnuts are a rich source of ALNA; small concentrations
are found in green leafy vegetables, corn oil, almonds,
hazelnuts, cereals, pulses, millets, and spices.78,142 Walnuts
and canola oil account for most of the ALNA in the western
diets.78,101 The recommended intake of ALNA is 2% of
energy but the current intake in the USA is 0.6% of
energy.11,74
ALNA is readily converted to EPA, and more slowly to
DHA; the latter being the major component of phospholipid
membranes of the brain and retina.78 The beneficial effects
of ALNA are less than half that of DHA and EPA, because
the conversion of ALNA to the more active longer-chain
metabolites is inefficient: <5%–10% for EPA, and 2%–5%
for DHA.80,141,143 This explains why vegetarians have lower
levels of n-3 PUFA than omnivores, and also higher platelet
aggregability.77 Since the biological effects of plant n-3
PUFA are significantly lower than marine n-3 PUFA, the
requirements may be higher (3% of energy) for vegetarians
than for nonvegetarians.9,74,77
Protein: Americans eat 80–90 g/day of protein, which is
twice the daily requirement, and most of this comes from
meat, which is also high in SAFA. Up to 25% of daily energy
from protein (but not more than 100 g/day) is permissible
if the major source of protein is plant-based. Nuts are
important sources of plant protein along with soy, bran,
beans, and legumes. Substituting protein for carbohydrates
increases HDL and lowers TG levels.144,145 In a meta-analysis
IHJ-584-03.p65
316
Table 5. Atherogenic, antiatherogenic, and neutral fatty
acids in selected meats and cooking oils6,147
Fat
Total Cholesterol- Stearic
Oleic acid:
SAFA
raising
acid:
cholesterol(%)
SAFA
cholesterol
lowering
(%)
neutral
MUFA (%)
SAFA (%)
Beef fat
Mutton fat
Chicken fat
Pork fat
Butter fat
Cocoa butter
Coconut oil
Palm kernel oil
Palm oil
51
54
30
39
66
61
92
74
50
29
29
24
27
53
26
89
71
46
22
25
6
12
13
35
3
3
4
39
33
42
45
28
35
7
14
39
of 38 controlled human clinical trials, consumption of soy
protein (47 g/day) was associated with a significant 13%
decrease in LDL, 10% decrease in TG, and a 2% increase in
HDL levels.146 This led to FDA approval for the use of food
labels for the health claim that soy protein can reduce the
risk of heart disease.
Meat: Although meat contains a significant amount of
SAFA, almost half the SAFA is stearic acid, which does not
raise TC levels. In addition, meat contains up to 45% of
cholesterol-lowering MUFA. Furthermore, lean meat has
much less SAFA than fatty cuts of meat (Table 5).6,147 Lean
beef is an excellent source of protein and MUFA, and has
less SAFA than chicken (dark meat); 6 oz of lean beef
contains 3.0 g of SAFA v. a chicken thigh which contains
5.2 g of SAFA (the term loin or round signifies lean meat
whereas prime or rib signifies fat cuts with very high SAFA
in the USA). Chicken and lean beef (not fatty meat) have
similar effects on plasma lipoproteins, and are
interchangeable in a healthy diet.30,148,149
Glycemic Load: A Potent Predictor of the
Metabolic Syndrome and Diabetes
The source, nature, and amount of carbohydrates have a
profound influence on postprandial glycemia, which in turn
is directly associated with the risk of CAD in patients with
diabetes.6,150,151 Foods containing the same amount of
carbohydrate (carbohydrate exchange) may have up to a
5-fold difference in glycemic impact, depending on the
differences in the digestion and absorption. 152,153 The
glycemic index is an extension of the fiber hypothesis, and
was proposed in 1981 as a physiological system for the
classification of carbohydrate-containing foods. 154,155
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Indian Heart J 2003; 55: 310–338
Carbohydrate classified by glycemic index, in contrast to its
traditional classification as either simple or complex, is a
better predictor of CAD in epidemiological studies.156 The
glycemic index is a scientific measure of the glycemic
response to various foods, and is obtained from published
food tables. The hierarchy of the glycemic index begins with
beans, lentils, rice, spaghetti, potatoes, white bread (with
refined flour), and refined grain cereals.150 A high glycemic
index indicates a lower quality of carbohydrate associated
with low HDL levels, and low rates of satiety. 157,158 Fruits,
nonstarchy vegetables, parboiled rice, and legumes have a
low glycemic index.159 The glycemic index of potato is
102%, white bread 100%, whereas that of apple is 55%,
and broccoli 13%. Glycemia observed after consuming dried
peas is only one-third that of an equivalent amount of
potatoes. Since peas are also high in fiber, their
consumption needs to be encouraged, especially in patients
with diabetes.153,160
Glycemic load is the product of the glycemic value of
the food and its carbohydrate content (per serving) divided
by 100. For example, carrot has a high glycemic index but
a low glycemic load (Table 6).152,161 The overall daily dietary
glycemic load is calculated by adding the glycemic loads of
all the different foods consumed in a given day. Accordingly,
the glycemic load can be decreased by reducing the amount
of carbohydrate intake and/or by consuming foods with a
low glycemic index. 162 In addition to the quality and
quantity of carbohydrates consumed, the glycemic load also
represents diet-induced insulin demand.163,164 PAI-1 levels
are significantly increased with high glycemic load, and
decreased with low glycemic load.165
Dietary carbohydrates drive TG much more than dietary
fat.6 A high glycemic load produces only mild increments
in TG levels in individuals with normal TG levels but
marked elevation in those with fasting lipemia and/or
obesity.6,166–168 A low HDL level is a strong risk factor for
CAD, even when the TC level is not elevated.169,170 A high
glycemic load produces a low HDL, particularly when
substituted for MUFA or PUFA.23,157,166,171–179 In a prospective
study of 75 521 women followed up for 10 years, those in
the highest quintile of glycemic load had double the risk of
CAD after adjustment for age, smoking status, total energy
intake, and other risk factors (p<0.0001).156
More importantly, a glycemic load promotes diabetes,
especially in those with insulin resistance.156,161,180–183
(Fig. 2)183 This is particularly true for refined carbohydrates,
sweets, white bread, and potatoes.45,156,183,184 Thus, a high
glycemic load may be considered a risk factor of equal
importance as high SAFA diet in precipitating diabetes. A
low glycemic load can reduce insulin secretion in patients
IHJ-584-03.p65
317
Enas et al. Prudent Diet and Preventive Nutrition 317
Table 6. Glycemic index of common foods152,161
Glycemic Serving Carbohydrate Glycemic
index
size
per serving
load
Basmati rice
58
Brown rice (South India) 50
Parboiled rice (Canada)
48
White rice (Uncle Ben’s) 45
Curry rice (Japan)
67
Jasmine rice
109
White bread
70
Uppuma
18
Upittu
68
Chapati
76
Dosai
77
Idli
77
Poori
70
Pongal
68
Millet/ragi
104
Barley
43
Tapioca
70
Kellogg’s cornflakes
81
Milk, full-fat
27
Yogurt
36
Orange juice
(reconstituted USA)
57
Pineapple
59
Plums
39
Prunes
29
Raisins
64
Cantaloupe
65
Plantain, green
38
Banana, unripe
70
Banana
53
Strawberry jam
51
Laddu
27
Black-eyed beans
42
Chickpeas
10
Kidney beans (rajmah)
13
Lentils
30
Lima beans
32
Pinto beans
39
Soy beans
15
Sweet corn
59
Green peas
39
Carrot
47
Beet root
64
Potato
85
Split peas
32
Snicker bar
55
Pizza Hut supreme
pan pizza
36
Coca Cola
58
Instant noodles
47
Macaroni
45
Spaghetti
68
11/19/2003, 11:27 PM
150 g
150 g
150 g
150 g
150 g
150 g
2 slices
150 g
150 g
60 g
150 g
250 g
150 g
250 g
70 g
150 g
250 g
30 g
250 g
200 g
38
33
36
36
61
42
30
33
42
30
39
52
41
52
50
37
18
26
12
9
22
16
26
16
41
46
21
6
28
23
30
40
28
35
52
16
12
24
3
3
250 ml
120 g
120 g
60 g
60 g
120 g
120 g
120 g
170 g
30 g
50 g
150 g
150 g
150 g
150 g
150 g
150 g
150 g
80 g
80 g
80 g
80 g
150 g
150 g
60 g
26
13
12
33
44
6
21
45
25
20
31
30
30
25
17
30
26
6
18
7
6
7
30
19
35
15
7
5
10
28
4
8
31
13
10
8
13
3
3
5
10
10
1
11
3
3
5
26
6
19
100 g
250 g
180 g
180 g
220 g
24
26
40
49
27
9
14
19
22
19
Indian Heart J 2003; 55: 310–338
318 Enas et al. Prudent Diet and Preventive Nutrition
Table 7. CVD risk reduction demonstrated with selected
food groups192–206
Author
Fig. 2. Risk of diabetes in 65 173 US women during 6 years of follow-up:
influence of glycemic load and fiber
with type 2 diabetes, decrease insulin requirements in type
1 diabetes, and improve glycemic control in both types of
diabetes. The incremental benefit from low glycemic load
is similar to that offered by pharmacological agents that
also target postprandial hyperglycemia, such as alphaglycosidase inhibitors.185,186 The benefit of low glycemic load
on the development of diabetes is similar to MUFA, PUFA,
whole grains, fiber, fruits, and vegetables.
Whole Grains: The Foundation of Healthy Food
Whole grains have been the staple food worldwide for
centuries, especially among vegetarians.187,188 Whole grain
and legume consumption not only decreases blood sugar
and insulin resistance but also prevents the development
of diabetes, particularly in people with the metabolic
syndrome.185,186 Whole-grain products are a good source
of fiber, minerals, as well as several vitamins, including
vitamins B and E. In a 12-year follow-up of 42 898 men,
the risk of developing diabetes was 42% lower in those with
the highest intake of whole grains. The risk was reduced
by 52% in those who also engaged in physical activity, and
87% in those who also had a low BMI.189 The risk reduction
was attributed to higher intakes of cereal fiber and
magnesium. Intake of whole-grain cereal is inversely
associated with hypertension, CAD, stroke, and CVD
mortality190,191 (Table 7).192–206 In another study, 25% –30%
reduction in stroke was observed with the intake
of whole grains—similar in magnitude to that of
statins.206–208 In sharp contrast, intake of refined grains
increases the risk of diabetes, stroke and CVD.191,205–212
These prospective data highlight the importance
of distinguishing whole-grain from refined-grain
cereals in the prevention of CVD and diabetes.209 Efforts
IHJ-584-03.p65
318
CVD risk reduction (%)
Fruits and vegetables (15%–48%)
Bazzano et al.192
25
Liu et al.193
15
Joshipura et al.194
30
20
Joshipura et al.195
Gaziano et al.196
48
Knekt et al.197
35
Nuts (19%–48%)
48
Albert et al.198
19
Ellsworth et al.199
Hu et al.200
35
Fraser et al.201
38
Fraser et al.202
40
Jiang et al.203
21 (diabetes)
Whole grains (32%–44%)
33
Jacobs et al.204
Fraser et al.201
44
Liu et al.205
32
Liu et al.206
32 (stroke)
should be made to replace refined-grain with whole-grain
foods.189
A whole-grain food includes all the edible parts of the
grain: the bran, the germ, and the endosperm.213 Grinding
or milling, using modern technology, leads to the loss of
many beneficial micronutrients, antioxidants, minerals,
phytochemicals, fiber, and much of the germ.214 As a result,
refined grain products are devoid of most vitamins and
essential fatty acids, and contain more starch.215 Because
of the loss of bran and pulverization of the endosperm,
refined grains are digested and absorbed rapidly, resulting
in a large increase in the levels of blood sugar and insulin.215
The common grains consumed in the West include wheat,
oats, rye, rice, barley, and corn.213 In the USA, rye bread is
an important source of whole grain consumption, and
results in a lower glucose response than white bread.152,212
Whole-grain, ready-to-eat cereal contains >25% whole
grain content by weight.189 The recommended intake is at
least 6 servings of grain (but not more than 11) with at
least 3 being whole grains. The current intake of whole
grains is less than half a serving/day or 15% of the grain
intake. Only 2% of the 150 lb of wheat flour consumed per
capita in the USA is whole-grain flour. 216 Commonly
consumed refined grain foods include white rice (idli, dosa),
refined wheat and flour (white bread), pancakes, cakes,
sweet rolls, English muffins, muffins, waffles, rolls, biscuits,
pizza, and refined-grain ready-to-eat breakfast cereal, and
their use should be minimized.
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Indian Heart J 2003; 55: 310–338
Enas et al. Prudent Diet and Preventive Nutrition 319
Nuts: A Wholesome Food and Powerhouse of
Healthy Fats and Nutrients
Extensive studies during the past decade have transformed
the image of nuts from fattening snacks to a wholesome
and heart-healthy food to be consumed daily.198–202,215 Nuts
are rich sources of protein, antioxidants, fiber, vitamins and
minerals (especially potassium and magnesium). Nuts yield
5%–10% fiber, and 12%–25% protein. The consumption
of nuts is also associated with a reduced risk of CAD in
several studies. 198–202,217,218 Yet, nuts are not generally
recommended as snacks because of their high fat content.
Although nuts contain 45%–80% fat, most of the fats are
the highly beneficial MUFA and PUFA (Table 8).65
Nuts, particularly almonds, significantly improve lipid
profiles because of the high fiber and MUFA component.
The dose–response effects of almonds were compared with
low-SAFA (<5% energy), whole-wheat muffins used as the
control diet in a randomized crossover study involving 27
dyslipidemic men and women. Three isoenergetic
supplements each (mean 423 kcal/day; 22% of energy)
were consumed for 1 month. The supplement consisted of
full-dose almonds (73 g/day), half-dose almonds plus halfdose muffins, and full-dose muffins. Full-dose almonds
produced a highly significant decrease in the Lp(a) level
(8%), LDL:HDL ratio (8%), and oxidized LDL (14%)
compared to the control diet.219 A 9% decrease in the LDL
level occurred with 73 g/day of almonds, and 4% decrease
with 37 g/day (handful) of almonds. This result translates
to a 1% reduction in LDL for every 7 g/day of almonds, and
is consistent with other studies.220,221 More importantly,
there was no difference in body weight between the almond
and muffin diet.222 Nuts are energy-dense, and contain
160–200 cal/oz. It cannot be overemphasized that energy
from nuts should replace the unhealthy calories from SAFA
and refined grains to prevent weight gain.
Consumption of other nuts (except coconuts) is equally
beneficial. For example, a 10% reduction in the LDL level
can be achieved by the daily consumption of 40 g of
walnuts, peanuts or pistachios, 70 g almonds, 100 g
macadamia nuts, and 110 g of pecans.223–230 Nuts are as
effective as increasing physical activity and trimming
calories to increase HDL levels. Adding 2 oz or 60 g of nuts
to a diet is a delicious way to decrease the TC/HDL ratio
and CAD risk. 8,14,23,231,232 Nuts also improve insulin
sensitivity and prevent diabetes.233 In a prospective study
of 83 818 women, 3206 new cases of type 2 diabetes were
observed during a follow-up of 16 years.203 Consumption
of nuts was inversely associated with the risk of type 2
diabetes after adjustment for age, body mass index (BMI),
physical activity, smoking, alcohol use, and dietary factors
(total calories, fat calories, and fiber). The risk of diabetes
was reduced by 27% in those who consumed >5 oz/week
of nuts or peanut butter compared to those who almost
never ate these products.203 The proscription of nuts can
no longer be justified. In fact, regular nut consumption as
replacement for refined grains and high-fat meats is
strongly recommended.161,234
Fruits and Vegetables, the Natural Way to Consume
Antioxidants and Flavonoids
Fruits and vegetables are rich in a myriad of nutrients and
phytochemicals, including fiber, vitamins B and C,
antioxidants, potassium, and flavonoids. 190,215
Phytochemicals are bioactive nonnutrient plant
Table 8. MUFA, PUFA, and SAFA content (in g) in tree nuts and fruit (all nuts are dry roasted without salt except coconut)65
Calories per 100 g
Fat content per 100 g
MUFA
PUFA
SAFA
Nuts
Macadamia nuts
Hazelnuts
Pecans
Almonds
Cashew nuts
Pistachio nuts
Walnuts
Flax seed
Coconut meat, creamed
Coconut meat, sweetened, shredded
718
646
710
597
574
570
607
492
684
501
76
62
74
53
46
46
57
34
69
35
59
47
44
34
27
24
13
7
3
2
1
8
21
13
8
14
37
22
1
0
12
5
6
4
9
6
4
3
61
31
Fruits
Avocados, California
Olives
Avocados, Florida
177
115
112
17
11
9
11
8
5
2
1
1
3
1
2
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320 Enas et al. Prudent Diet and Preventive Nutrition
compounds linked to a reduced risk of chronic diseases.
Fruits and vegetables decrease blood pressure,
homocysteine, and cancer, especially that of the GI
tract. 211,235,236 Since fruits and vegetables are rich in
potassium, their liberal intake is recommended for the
prevention and treatment of hypertension.237 Good sources
of potassium include bananas, oranges, beans, fish, and
dairy products. While you can get an overdose of potassium
from pills, you cannot get an overdose of potassium from
food. Moreover, dietary supplements do not have the health
benefits associated with a diet rich in fruits and vegetables.
For example, the antioxidant value of 100 g of apple is
equivalent to 1500 mg of vitamin C.3
Several large studies, including one comprising 84 000
women and 42 000 men, have shown a significant inverse
association between the consumption of fruits and
vegetables and CVD mortality 190,194,195 (Table 8). The
relationship is particularly strong with vitamin C-rich
fruits, green leafy vegetables, and carotenoid vegetables
(carrots, broccoli, spinach, lettuce, tomatoes, and yellow
squash).192–196,238,239 Consuming fruits and vegetables (3
times/day compared with <1 time/day was associated with
a 27% lower incidence of stroke, a 42% lower stroke
mortality, a 24% lower CAD mortality, a 27% lower CVD
mortality, and a 15% lower all-cause mortality after
adjustment for standard CVD risk factors.192 In sharp
contrast, consumption of potatoes and French fries increase
the risk of CAD and stroke.152,215
The landmark study of the Dietary Approaches to Stop
Hypertension (DASH)240 has yielded tremendous insights
into the benefits of increased intakes of various types of
fruits and vegetables. The DASH diet is rich in vegetables,
fruits, and low-fat dairy products (9 servings of fruits and
vegetable combined per day).240 As compared with the
control diet with a high sodium, the DASH diet with a low
sodium intake led to a decrease in systolic blood pressure
of 7 mmHg in normotensive individuals, and 11.5 mmHg
in hypertensive individuals. The benefits of the DASH diet
on lipoprotein levels were equally spectacular, with an 11
mg/dl decrease in LDL and a 4 mg/dl increase in HDL levels
without significant effects on TG levels. Men had a greater
reduction in LDL level than women, with no difference
between Whites and Blacks. These results suggest that the
DASH diet is likely to reduce the risk of CAD and can be
recommended as an overall eating plan.241 The current
intake of fruits and vegetables is 3 servings/day each in the
USA; only 23% consume the recommended 5 servings/day
each.242 The DASH diet is feasible in the real world, unlike
the array of drastic diets which are impossible to continue
for more than a few months.240
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Indian Heart J 2003; 55: 310–338
Flavonoids: Flavonoids are secondary metabolites that
plants use to attract pollinators, repel predators, and to
color flowers, leaves, and fruits.243 Important biological
effects of flavonoids include the scavenging of oxygenderived free radicals, inhibition of LDL oxidation, increase
in HDL levels, and protection against CVD and several
chronic diseases. 244–248 The beneficial effects of these
natural products on health were known long before the
discovery of flavonoids. The major sources of flavonoids are
vegetables (onions, kale, broccoli), fruits (apples, grapes,
berries), olive oil, and beverages such as tea and
wine.244,248,249 Other sources include grains, bark, roots,
stems, and flowers. Flavonoids present in red wine could
be partly responsible for the low CAD mortality seen in red
wine drinkers (“French Paradox”). Red wine is the major
source of flavonoid in France and Italy (40%), onions and
apples in Finland, and olive oil in Greece.250 The strong taste
of extra-virgin olive oil is partly caused by the abundance
of flavonoids.
Antioxidants: Oxidative modification of LDL accelerates
atherosclerosis whereas dietary antioxidants prevent LDL
oxidation. These antioxidants include vitamin C, vitamin
E, beta-carotene, selenium, flavonoids, magnesium, and
MUFA.251 It is worth emphasizing that vitamin pills are no
substitute for a healthy diet. Although an earlier study
suggested some benefits from antioxidant vitamin
supplementation, several subsequent studies involving
more than 100 000 patients have consistently failed to
demonstrate any benefit. More recent studies suggest that
possible harm may outweigh the benefit of these
vitamins.252–254 In a recent study, the use of vitamins E and
C reduced the lipid-lowering efficacy of statins and niacin
by 50%. More importantly, the clinical event reduction was
lowered from 90% to 60%. 255 The current scientific
evidence does not support any protective role of vitamins
E, C, and beta-carotene supplements; their use only creates
a diversion away from proven therapies. 256 The US
Preventive Service Task Force (USPSTF) recommends
against the use of beta-carotene supplements.257 It is worth
noting that the oxidative modification of LDL continues to
be relevant, and people should obtain their antioxidant
vitamins from food sources. (However, folic acid fortification
is recommended in women who are pregnant or might
become pregnant.)
Non-nutritive Food Adjuncts
Fiber: The term dietary fiber was coined to describe the
plant cell wall removed during the refining process.258
Dietary fiber improves coagulation, fibrinolysis, insulin
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Indian Heart J 2003; 55: 310–338
sensitivity, LDL, and blood pressure levels.259–265 Fiber is
particularly concentrated in bran. Insoluble fiber shortens
the intestinal transit, resulting in less time for carbohydrate
absorption.266 Soluble (viscous) fiber, such as beta-glucan,
which is found in oat bran, delays gastric emptying, and
slows the absorption and digestion of carbohydrates. These
processes lead to a slower release of glucose into the
circulation, resulting in a reduced demand for
insulin.187,189,267 An intake of 16 g of total fiber is associated
with a 12% decrease in CAD risk.268 FDA has permitted
cardiovascular health claims to be made by the industry
for 2 viscous fibers, beta-glucan and psyllium.269 Psyllium
supplementation significantly lowers TC and LDL levels; it
is safe and well tolerated.270
The benefit of whole grains appears to be mediated
primarily through the greater intake of fiber, and is greater
with cereal fiber than vegetable or fruit fiber.212,263,264,271,272
Approximately one-fourth of the fiber provided by cereal
sources is water soluble.268 Cereal fiber consumption is
associated with a 21% lower risk of incident CVD, and 30%
lower risk of diabetes. 164,188,259,273 (Fig. 2). Cereal fiber
consumption may reduce the risk of CVD via the
substitution effect, replacing the intake of other foods
having potentially detrimental effects. In addition to cereal
grains, legumes are also excellent sources of water-soluble
dietary fiber. Half a cup of cooked beans contains, on an
average, 6 g of total fiber and 2 g of soluble fiber.274
The current ADA recommendation for a healthy diet is
to consume 25 g/day of fiber with about one-third from
soluble fiber. In one study, type 2 diabetics consuming 50
g/day of fiber (25 g soluble, 25 g insoluble) lowered the
blood sugar by 13 mg/dl, plasma TC by 7%, and TG levels
by 10%.275 Thus, a high intake of dietary fiber, above the
level recommended by the ADA, particularly of the soluble
type, improves glycemic control, insulin levels, and plasma
lipid concentrations in patients with type 2 diabetes.275
Plant sterols and stanols: Plant sterols and stanols are
structural analogues of cholesterol. Low-fat plant stanolcontaining margarines lower plasma LDL levels (by as much
as 12%) in those with hypercholesterolemia by suppressing
cholesterol absorption.276–279 In one randomized controlled
study, the reduction in LDL with such supplements was
similar to 20 mg of lovastatin (30% with statin v. 28.6%
with diet).280 Various plant supplements have been shown
to reduce LDL by 40% (Table 9).146,219,265,280–283
Spices: Plants have the capacity to synthesize a diverse
array of chemicals. Spices are aromatic vegetable
substances, the significant function of which is food
seasoning rather than nutrition. Typically, spices are the
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Enas et al. Prudent Diet and Preventive Nutrition 321
Table 9. A portfolio of dietary factors useful for LDL
reduction146,219,265,280–283
Decrease in LDL(%)
SAFA intake
Dietary cholesterol intake
Body weight
Plant sterols/stanols
Soy protein
Nuts (almonds)
Viscous fiber intake
Total LDL reduction
<7%
<200 mg
5 kg
1–3 g/day
25 g/day
50 g/day
5–10 g/day
Full portfolio
10
5
5
5
5
5
5
40
dried aromatic parts of plants, generally the seeds, berries,
roots, pods, and sometimes leaves, that mainly grow in
tropical countries. Common spices include turmeric,
paprika, saffron, cinnamon, nutmeg, red and black pepper.
In contrast, herbs used in cooking are typically composed
of leaves and stems.284
Caffeine: Caffeine is found in coffee, tea, soft drinks,
chocolate, and some nuts. Finland has one of the highest
rates of per capita coffee drinking (13 kg/year).285 In a
prospective study of 20 179 Finnish adults, coffee drinking
was not associated with an increased risk of MI. However,
consumption of large quantities of boiled unfiltered coffee
raises cholesterol and homocysteine levels.285–287 In an
experiment involving 10 volunteers, who consumed the
equivalent lipid content of 6–7 cups of boiled unfiltered
coffee daily for 6 weeks, the LDL levels increased by 33 mg/
dl.288–290 These data suggest that daily consumption of 1–2
cups of coffee is safe with no particular health benefits or
risks.
Tea: Tea, the most widely consumed beverage in the world
other than water, has been associated with lower
cardiovascular risk.291–295 Unlike coffee, tea consumption is
associated with a substantial reduction in LDL levels. Tea is
rich in flavonoids. Green tea contains catechins, whereas
black tea, formed from the polymerization of catechins,
contains theaflavins.291 In one recent study, theaflavinenriched green tea extract reduced the LDL level by 16%.296
Tea is the major source of flavonoid intake in Japan (>80%);
the Japanese consume an estimated 7 cups/day of tea
compared to half a cup/day in the USA. Adding milk to
tea, as is common in the UK and India, abolishes the
beneficial effect of tea.297
Alcohol: Moderate intake of alcohol (one drink a day for
women and 2 drinks a day for men) may decrease the risk
of CAD.298 Recently, it has been shown that only one drink
per week is enough to provide cardiac protection (45 ml of
spirits or 350 ml of beer or 120 ml of wine); the
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322 Enas et al. Prudent Diet and Preventive Nutrition
cardioprotection is similar for beer, wine, whiskey, brandy,
vodka, rum, and drinks in equivalent amounts.299,300 More
than 2 drinks per day does not provide any additional
protection and, in fact, the net effect may be harmful until
the age of 45 years in men and 55 years in women.301 Like
carbohydrates, consumption of large quantities of alcohol
raises TG levels.6,302 Other dangers of excessive alcohol
consumption includes alcohol dependence, liver disease,
high blood pressure, obesity, stroke, traffic accidents,
spousal abuse, suicide, and breast and other cancers. Given
these risks, the American Heart Association cautions
people against increasing their alcohol intake or starting
to drink if they do not already do so.
Weight Gain and Weight Loss Diets
Excess calories and obesity: Diets of any type containing
more energy than needed or expended will lead to obesity
and dyslipidemia.303 A calorie is a calorie whether it comes
from carbohydrates, fat, or protein. Excess calories of any
kind will eventually be converted by insulin to body fat.304
A common misconception is that dietary fat of any kind is
fattening, while low-fat and high-protein diets have
slimming properties. It is absolutely vital that both
physicians and the public understand that it is the excess
calories and not diet composition that causes weight
gain.304–309 There is no evidence of weight gain with a high
MUFA diet, compared with a high carbohydrate diet, under
isoenergetic conditions.310,311
Obesity is not only a reflection of overnutrition but also
an important contributor to the mass dyslipidemia seen in
India and western countries. 6 Obesity in general is
accompanied by the increased production of apo B and a
decrease in the HDL levels.6,312 Humans have a limited
capacity to store energy as carbohydrates. When
carbohydrate intake exceeds storage and oxidation
capacities, the excess is converted to fat by de novo
lipogenesis that leads to high TG levels.313 This process is
increased several-fold in people with the metabolic
syndrome which, if left untreated, leads to overt diabetes
(25-fold risk).312 Body fatness and not lean body mass is
the principal determinant of diabetes and prediabetes.314
At a given BMI, Asian Indians have 7%–10% higher body
fat; accordingly, BMI <23 is termed optimum; BMI 23–25
overweight, and >25 obese in Asian Indians. Likewise, the
optimum waist circumference is lower in Asian Indians
than Whites with a cut-off <90 cm in men and <80 cm in
women. 315 Although obesity and dyslipidemia are
uncommon in less affluent societies, some individuals may
be excessively sensitive to caloric excess.6
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Fast foods rapidly produce plaques. The average
American gained 9 lb in the past decade. A third of
vegetable taken in the USA are either French fries or potato
chips.305 In one study, overweight subjects who consumed
fairly large amounts of sucrose (28% of energy), mostly as
beverages, had increased energy intake, body weight, fat
mass, and blood pressure after 10 weeks. These effects were
not observed in a similar group of subjects who consumed
artificial sweeteners.316 Restricting the dietary cholesterol
can achieve a 3% reduction in TC level, whereas losing
weight from trimming extra calories can reduce LDL by 5%
to 20%.8
Weight loss: The recipe for effective weight loss is a
combination of motivation, physical activity and caloric
restriction; maintenance of weight loss is a balance between
caloric intake, and physical activity, with life-long
adherence. Each pound of body fat contains 3500 cal.
Therefore, a person who consumes 500 cal less than he
spends each day can lose 1 lb of fat a week. Any higher
weight loss is due to a more severe caloric restriction or
water loss rather than fat loss. The minimum caloric intake
in a medically unsupervised weight loss diet is 1500 cal/
day for men, and 1200 cal/day for women. Superior longterm participation and adherence is observed in a high-fat
diet rather than a low-fat diet (35% v. 20%), especially in
western cultures.309 The greater success rate is due to higher
palatability of the high-fat diet provided by mixed nuts and
lean meat.309 Furthermore, the long-term outcome of a
reduced-fat diet consumed ad libitum for weight control is
dismal. In one study, compared with the control group,
weight decreased in the reduced-fat diet group significantly
by 3 kg in 1 year but diminished to an insignificant 1 kg by
5 years.317 Until more information becomes available, “the
prudent diet,” which is a balanced diet, is the one to follow
for young and old alike.318
Very low fat diet: Some experts have argued for a very
low-fat diet (<10%).319 Since these diets are not highprotein diets (like the Atkins diet), they are in reality very
high in carbohydrate. High-carbohydrate diets (the
Macrobiotic diet) increase insulin resistance and induce the
metabolic syndrome. In controlled trials, low-fat, highcarbohydrate diets decreased HDL levels. Replacing 10%
of energy from SAFA with carbohydrate lowers the HDL
levels by 5 mg/dl, even when the carbohydrate consumed
is complex.62,173,320,321 There is also a marked increase in TG
level, which makes LDL small, dense, and more
dangerous. 173,320–322 The effect is strongest when
carbohydrates replace SAFA but is also seen when
carbohydrates replace MUFA and PUFA. The effect is seen
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in both short- and long-term trials, and is therefore not a
transient phenomenon. Therefore, replacement of SAFA
must be achieved through increasing MUFA and not by
carbohydrates. The adverse effects of high-carbohydrate
diets (high glycemic load) in the metabolic syndrome and
diabetes have not received due attention, especially in the
Indian literature. The recommended carbohydrate intake
is <50% of calories in people with the metabolic syndrome
or diabetes (NCEP).
The allure and dangers of very low-carbohydrate,
high-protein diets: High-protein diets that are extremely
low in carbohydrates are touted as a new strategy for
successful weight loss by many.323 Most such diets contain
<10% carbohydrates, 25%–35% protein, and 55%–65%
fat. Because the protein is provided mainly by animal
sources, these diets are high in SAFA and cholesterol. Thus,
these diets are truly high-fat diets masquerading as highprotein diets. Advocates of this diet often promote serious
misconceptions about carbohydrates, insulin resistance,
ketosis, and fat burning as the mechanisms of action for
weight loss. To avoid excess load on the kidneys, the total
protein intake should not exceed 100 g/day. 324 More
importantly, the body has an obligatory requirement for
glucose of about 100 g/day, largely determined by the
metabolic demands of the brain.324,325
In randomized studies, the extent of weight loss was
small (4 kg), and adherence to the diet was low.326,327 In
one study, although a low-carbohydrate diet produced a 4%
greater weight loss at 6 months than did the conventional
diet, the differences did not persist at 1 year. Furthermore,
adherence was poor, and attrition was high in both the
high- and low-carbohydrate groups. Longer and larger
studies are required to determine the long-term safety and
efficacy of low-carbohydrate, high-protein, high-fat diets.326
Two recent studies have provided insight into high-protein
diets; the initial weight loss is due to fluid loss and ketosisinduced appetite suppression. The monotony of this diet
also results in involuntary caloric restriction.326,327
The beneficial effects on blood lipids and insulin
resistance are due to the weight loss, and not the change in
caloric composition. Such diets increase LDL but decrease
TG levels, in sharp contrast to high-carbohydrate diets,
which increase TG, and decrease HDL levels. Although
these diets may not be harmful for most healthy people over
a short period of time, there are no long-term scientific
studies to support their overall efficacy and safety. Markedly
atherogenic profiles have also been reported in children
with ketogenic diets. At 6 months, the high-fat ketogenic
diet significantly increased plasma LDL levels by 50 mg/dl,
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Enas et al. Prudent Diet and Preventive Nutrition 323
triglycerides 58 mg/dl, apo B 49 mg/dl, and non-HDL
cholesterol 63 mg/dl. The mean HDL-cholesterol levels
decreased significantly.328 These lipid abnormalities in
children are more than likely to translate into a high risk
of heart disease as young adults.
High-protein diets also do not provide the variety of foods
needed to continue the diet on a long-term basis. Highprotein diets are not recommended, and are perhaps
dangerous because they restrict most healthful foods that
provide essential nutrients, especially fruits and vegetables.
Individuals who follow these diets are therefore at risk for
compromised vitamin and mineral intake, as well as
potential cardiac, renal, bone, and liver abnormalities
overall.324 The consumption of a very low-carbohydrate diet
for 6 weeks delivers a high acid load to the kidney, increases
the risk of stone formation, decreases body calcium, and
may increase the risk of bone loss and fractures.329 A highprotein diet is the ultimate antithesis of the prudent diet. It
is important to realize that diets are not for 6 weeks, 6
months or 6 years, but for a lifetime. Although most quickfix diets have a short-term success rate >90%, the longterm failure rate is 100%.
Healthy and Contaminated Vegetarian Diets
Omnivores or nonvegetarians outnumber vegetarians 10
to 1 in western cultures. Vegetarians include vegans who
do not consume any animal products, ovo-vegetarians who
consume egg, lacto-vegetarians who consume milk, ovolacto-vegetarians who consume egg and milk, and semilacto-vegetarians who eat small amounts of meat (<1 time/
week). Ironically, most self-defined vegetarians in western
countries consume red meat and poultry, albeit
infrequently, and in very small quantities. In a recent
survey, only 1% of self-reported vegetarians did not eat meat
in the USA, whereas about 6% of Americans who do not
consume any meat did not identify themselves as
vegetarians.330–332
Western vegetarians generally consume a healthier diet
than omnivores; healthy foods such as soy, nuts, legumes
and vegetables replace meat.333 They generally have twice
the fish consumption of nonvegetarians.330 This is not the
case with Indian vegetarians who shun fish. US vegetarians
eat more whole-grain products, dark green and deep yellow
vegetables, whole-wheat bread, brown rice, soy milk, tofu,
meat substitutes, legumes, lentils, garbanzos, walnuts, and
pecans.330 However, they eat the same amount of food as
omnivores (1000 kg/year) but are usually thinner.334 A
healthy vegetarian diet is characterized by more frequent
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324 Enas et al. Prudent Diet and Preventive Nutrition
consumption of fruits and vegetables, whole grains,
legumes and nuts, resulting in higher intakes of dietary
fiber, antioxidants and phytochemicals. 335 Thus a
vegetarian diet contains a portfolio of natural products that
can improve both the carbohydrate and lipid abnormalities
in diabetes.187
Vegetarians eat about two-thirds of SAFA, and one-half
of cholesterol as omnivores; vegans consume one-half of
SAFA and no cholesterol.9,336 Cholesterol levels among
western vegetarians are 15–25 mg/dl lower than
omnivores.337–340 Vegans have very low levels of LDL.341,342
Nuts, viscous fibers (from oats and barley), soy proteins,
and plant sterols in vegetarian diets improve serum lipid
levels.337 Furthermore, substituting soy or other vegetable
proteins for animal proteins reduces the risk of developing
nephropathy in type 2 diabetes.
With the exception of tropical oils, calories from plant
sources are negatively correlated with CAD mortality,
whereas calories from animal sources are positively
correlated. 16 Olive oil, fresh fruits, and vegetables are
protective against heart disease, and seem to play a greater
role in the French paradox than wine. 16 Greater
consumption of whole milk and other animal products
were important contributors to Finland having the highest
rates of CAD.16 In a prospective study of 4671 vegetarians
and 6225 nonvegetarians, followed up for 10–12 years,
BMI, TC, and CAD mortality was substantially lower among
vegetarians than in the nonvegetarians. Other studies also
suggest a protective effect of vegetarianism against many
diseases. Vegetarians in western countries, but not in India,
enjoy remarkably good health, exemplified by low rates of
obesity,334,343 diabetes,344 CAD345–347 and cancer,337 and a 3–
6 year increase in life expectancy.333,348 It is not clear
whether this is due to abstinence from meat or to a greater
consumption of heart-healthy food.349
Indian vegetarianism, a form of “contaminated
vegetarianism”: Most Asian Indians are lacto-ovovegetarians, unlike western vegetarians. About 50% of
Asian Indians are vegetarians, but their lipoprotein levels,
and rates of diabetes and CAD are no different from those
of nonvegetarians. 350,351 This phenomenon is due to
contaminated vegetarianism, wherein vegetarians manage
to consume excessive amounts of SAFA and TRAFA. In the
CADI study, Asian Indian physicians in the USA followed a
heart-healthy diet, with 32% energy from total fat, and 8%
from SAFA, which is the recommendation by the NCEP.350
This appears to be an exception rather than the rule. In a
Canadian study, Asian Indians consumed more fried foods
and high-fat dairy products, such as full-fat milk than White
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Canadians.352 Although the intake of fat is 20%–25%
energy in most Asian countries, many affluent Asian
Indians consume >50% of their calories from fat.
Indian vegetarians consume liberal amounts of bakery
products, butter, ghee, cheese, ice cream, curd, and other
dairy products to overcompensate for not using meat.
Contrary to popular belief, dairy products are the major
source of SAFA, even in the western diet. It is worth
highlighting that SAFA intake from high-fat dairy products
increases LDL levels 3 times as much as it raises the HDL
level.353 Meat is expensive, and consumed in very small
quantities by Indian omnivores because of cultural and
financial reasons. This is in sharp contrast to an annual
per capita consumption of 124 kg meat and 23 kg fish by
Americans. 354 Prolonged cooking of vegetables, as is
practised in India, virtually destroys every nutrient before
it is consumed. A major problem overlooked in the Indian
diet is the high glycemic load, resulting in high TG and low
HDL levels. 355 There appears to be a threshold for
carbohydrate consumption with an intake >280 g/day
often resulting in atherogenic dyslipidemia.350
Deep-frying and reuse of frying oil: Deep-frying, a
common form of cooking among Asian Indians, is
associated with spontaneous hydrogenation, and the
formation of TRAFA. Reuse of oil used for deep-frying has
been shown to produce endothelial dysfunction. 356
Repeated reuse of such oil is exceedingly common among
Asian Indians.357 HDL inhibits LDL oxidation primarily
through its paraxonase activity; reuse of frying oil reduces
paraxonase activity, and thus reduces the ability of HDL to
prevent LDL oxidation.356–360 Fats that have been heated for
prolonged periods in air contain many dangerous products
from oxidation and breakdown of lipids. These compounds
include hydroxy peroxides, aldehydes, polymers, hydroxy
fatty acids, hydroperoxy epoxides, and hydroperoxy
alkenals.361 In one study, fast-food restaurant cooking oil,
just before the weekly change, was compared to unused oil.
The repeatedly used oil had 4 times higher peroxide levels,
7 times higher carbonyl levels, and 17 times higher levels
of acids.357
Ghee: Ghee is one of the most important sources of dietary
fat and a common cooking medium.362,363 Use of ghee for
deep-frying is considered gourmet among Asian Indians.
Ghee or clarified butter is anhydrous milk fat, and is rich in
MUFA (32%) and SAFA (62%), most of which are
cholesterol-raising (myristic acid 17%, palmitic acid 26%).
It is perhaps more harmful than butter due to the added
presence of cholesterol oxides, which are generated during
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its preparation by prolonged heating of butter.362–364 Liberal
dietary exposure to cholesterol oxides from ghee is a likely
contributor to the high frequency of CAD among Asian
Indians.364 There are conflicting data on the risk of heart
disease with ghee.365,366 We are unaware of any biological
explanation as to why Asian Indians can be immune to the
unfavorable effects of butter and/or ghee. In addition to milk
ghee, vegetable ghee (vanaspathi) is also immensely popular
in Indian cooking, which exerts similar adverse effects
through its high TRAFA content.
Tropical oils: The term tropical oils refers to coconut, palm
kernel, and palm oils. These oils contain a very high
percentage of SAFA, unlike other vegetable oils such as
rapeseed oil (mustard oil), sesame oil, and rice bran oil,
which are low in SAFA and high in MUFA (Table 3). Tropical
oils are more atherogenic and thrombogenic than mutton
and beef fat; the latter contains <5% myristic acid
compared to 18% in coconut and palm kernel oils.104 In
fact, these oils contain more TC-raising SAFA than animal
fats—coconut oil 89%, palm kernel oil 71%, and palm
oil 46% compared to <30% for butter fat, beef fat, pork
fat, and chicken fat (Table 5).6,147 Tropical oils account
for <2% of energy (<4 g/day) in the USA. but 25%
or more in many other countries.147,367 Tropical oils are
also found in commercially baked cakes, biscuits, cookies,
and “snack foods”. In Mauritius, a regulated change in the
SAFA content by substituting soybean oil for palm oil
resulted in a dramatic 32 mg/dl fall in TC level, and
underscores the crucial role of cooking oils in population
levels of TC.368
Coconut oil: Coconut oil contains mostly cholesterolraising SAFA (8% caprylic, 6% capric, 45% lauric, 17%
myristic, and 8% palmitic acid).369 Rabbits fed a commercial
chow diet containing 0.5% cholesterol and 14% coconut
oil developed more severe dyslipidemia and atherosclerosis
than rabbits fed the same diet containing olive oil instead
of coconut oil. The average plasma TC level was 2-fold, and
TG level 20-fold higher in the coconut oil-fed rabbits than
in the olive oil-fed rabbits.28 Cox et al.369,370 have reported
the cholesterol-raising effects of coconut oil to be similar
to that of butter. In a comparative study of diets rich in
beef fat versus coconut oil, the plasma TC, LDL, and HDL
responses were lower with beef fat than coconut oil,
commensurate with the lower proportion of cholesterolraising SAFA in beef (29%) than coconut oil (89%)371 (Table
5). A Malaysian study in which 22% of the energy intake
was substituted with coconut oil found an increase of 40
mg/dl in TC, 29 mg/dl in LDL, 36 mg/dl in TG, and 4 mg/dl
in HDL levels.372 The impact on LDL and HDL by using
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Enas et al. Prudent Diet and Preventive Nutrition 325
various fats as the sole source of fat in a Dutch population
is shown in Fig. 1. Note the marked increase in LDL in
contrast to HDL with the use of coconut oil.
Kerala, renowned for the universal and liberal consumption of coconut milk and oil, not only has the highest level
of TC in India, but also the highest rate of CAD.373 The
proportion of subjects with high TC (>239 mg/dl) in Kerala
is almost double that of the USA. (32% v. 18%).374 This is
in sharp contrast to the Japanese among whom only 6%
have high TC.375 In Sri Lanka, which also has a very high
rate of CAD, about 80% of the fat in the habitual diet comes
from coconut.134,374,376
Consumers need to be educated about the atherogenic
and antiatherogenic effects of various cooking oils, as well
as animal and vegetable ghee. There is little awareness, and
even controversy, about the atherogenic effects of certain
foods and oils, especially in regions where the production,
sale, and consumption of such oils have a profound impact
on the regional economy.
Prudent Diet for All Ages and the Entire
Population
The traditional Mediterranean diet is characterized by
abundant plant foods (vegetables, breads, pastas, beans,
nuts, and seeds). Fresh fruit is the typical daily dessert, and
olive oil is used as the principal source of fat. Dairy products
(principally cheese and yogurt), fish, and poultry are
consumed in low-to-moderate amounts. Red meat and egg
are consumed in low amounts (0–4 eggs weekly). Wine is
consumed in low-to-moderate amounts, normally with
meals. This diet is typically high in total fat (35%–45%) but
low in SAFA (7%–8% of energy). Greater adherence to the
traditional Mediterranean diet is associated with a
significant reduction in total mortality.377 The 6 beneficial
components of this diet have recently been elucidated. They
are vegetables, legumes, whole-grain cereal, fish, fruit, and
nuts, which form the basis for the “prudent diet” 377
(Table 10).199–203,225–227,231–236
According to the new paradigm, dietary pattern rather
than individual nutrients appears to be more important.
Recent research suggests the existence of a food synergy in
which the beneficial effects of healthy foods are magnified
when several different types of foods are consumed.213 Hu
et al. have developed the concept of “prudent diet” (modified
from the Mediterranean diet).30,378–380 The “prudent diet”
has a higher intake of vegetables, fruits, legumes, whole
grains, fish, and poultry, whereas the “western diet” is
characterized by a higher intake of red meat, processed
meat, refined grains, sweets, desserts, French fries, and
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326 Enas et al. Prudent Diet and Preventive Nutrition
Table 10. The benefits and sources of selected heart-healthy foods199–203, 225–227, 231–236
Category
Benefits
Sources/preferred foods
Whole grains
Good source of fiber, minerals, and
vitamins E and B
Delay gastric emptying and blunts postprandial
insulin response
Improve insulin sensitivity
⇓ Insulin secretion
⇓ Insulin resistance, and diabetes
Improve lipids (⇑ HDL)
⇓ Hypertension
⇓ CVD incidence and CVD mortality
Whole wheat, oats, rye, barley, corn, brown rice
and wild rice
Whole-grain oatmeal, whole-grain,
pumpernickel, rye or dark bread
Whole-grain, ready-to-eat cereal
Cooked cereal
Pasta
Popcorn
Bran
Buckwheat, cracked wheat, wheat germ
Fruits and vegetables
Rich in fiber, flavonoids, and antioxidants
⇓ Blood pressure
⇓ LDL
⇑ HDL
⇓ Homocysteine
⇓ CVD and mortality
⇓ Cancer, especially GI tract
⇓ All-cause mortality
Green leafy vegetables
Carotenoid vegetables (carrots, broccoli, spinach,
lettuce, tomato, and yellow squash)
Citrus (vitamin C-rich) fruits
Temperate fruits (cantaloupe, apple, pear)
Tropical fruits (mango, papaya, pineapple,
jackfruit, guava, banana)
Viscous fiber
⇓ LDL
⇓ Postprandial glycemia
Cereal grains (oats—beta glucan)
Legumes, Psyllium (Metamucil)
Soy protein
⇓ LDL
Soy bean
Plant sterols and stanols
⇓ LDL
Low-fat plant stanols containing margarines
Nuts
⇓ LDL
⇑ HDL
See Table 6
high-fat dairy products. 378,380 The “prudent diet” is
associated with a 24% decreased risk of CVD compared to
a 46% increased risk with the western diet.215,380
Consumers are bombarded on a daily basis with the
Babel of nutritional breakthroughs.381 Food companies
advertize their products, nutrition researchers publicize
their latest results, and the media are more interested
in a controversial story than in scientific facts.30 Trivial
reports are often publicized as major breakthroughs by
the media, and cause confusion among consumers. It is
difficult for most journalists and consumers to tell the
difference between a major research finding and a trivial
report.381
The dangers of the current western diet and the
contaminated vegetarian diet, and the remarkable benefits
of the prudent diet need to be disseminated among
cardiologists, physicians, and the public. This diet can be
sustained lifelong but needs to be adapted to Indian
ingredients and cooking methods. Several countries have
developed dietary guidelines to reduce nutritional
information anarchy. The Indian consensus on the prudent
diet should incorporate scientific facts, and the cultural
preferences appropriate for different parts of India. Such
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326
information needs to be adopted by the scientific
community, and adapted by the food industry.
Current Knowledge on Preventive and
Therapeutic Nutrition
Randomized, controlled clinical trials, meta-analysis, and
systematic reviews are considered the ultimate tests of the
benefits of therapeutic interventions. Such reviews have
shown a 24% reduction in major coronary events in dietary
trials lasting >2 years.382 The TC/HDL ratio is the single best
lipid predictor of CVD. This ratio is determined by 3 partly
opposing dietary factors—the proportion of energy from
SAFA, which raises TC; the proportion of energy from total
fat, which raises HDL; and the excess in total energy intake,
which produces obesity and secondarily lowers HDL.20 The
greatest reduction in CVD risk is achieved by LDL-lowering
by reducing SAFA intake. Decreasing SAFA intake is best
accomplished by reducing the intake of high-fat dairy
products, and increasing fiber-rich foods. A diet
incorporating lean beef, skinless chicken, and fatty fish has
been shown to improve the lipid profile by 5%–10%.383
The preferred replacement for SAFA is MUFA or PUFA
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Indian Heart J 2003; 55: 310–338
and not carbohydrates (Table 11). Replacing SAFA with
carbohydrates decreases the LDL levels but makes LDL
small, dense, and more dangerous by increasing the TG
levels.30 Substituting carbohydrates with MUFA decreases
the LDL level, and increases the HDL level. PUFA and MUFA
increase insulin sensitivity, and decrease the risk of type 2
diabetes.45,384–386 Substantial evidence indicates that diets
using MUFA and PUFA as the predominant form of dietary
fat, an abundance of fruits and vegetables, and adequate
n-3 fatty acids can offer significant protection against CAD,
stroke and diabetes (Table 8). Adequate consumption of
fruits and vegetables provides most of the necessary
antioxidants, and are preferable to dietary supplements in
the form of pills. Replacing a high glycemic with a low
glycemic index, and reducing the glycemic load can reduce
the risk of diabetes161 (Table 6).
Nuts, once deemed unhealthy because of their high fat
content, have become an important part of diets designed
to control weight, lower blood pressure and cholesterol, and
achieve secondary prevention of CAD, besides adding
variety, texture and flavor to dishes.145,211,215,387 Unless a
beneficial effect is clearly demonstrated by well-designed
scientific studies, the liberal use of butter, ghee, palm oil,
Enas et al. Prudent Diet and Preventive Nutrition 327
and coconut (oil and milk) should be discouraged. However,
in diets with a negligible intake of fish, meat, milk, and dairy
fat, the modest use (<7% of energy) of such oils may be
preferable to no fat at all.
Practical Recommendations
Better food habits can help reduce the risk of diabetes, MI,
stroke, and death. A healthy eating plan means choosing
the right foods to eat, and preparing them in a healthy way.
A healthy diet involves a decrease in the use of refined
grains, tropical oils, egg yolks, animal, dairy, and
hydrogenated fats, and an increase in the consumption of
whole grains, vegetables, nuts, legumes, and fruits. 7
Increasing the MUFA intake up to 20% of energy, as a
replacement for SAFA and carbohydrates, may help prevent
and treat the metabolic syndrome, diabetes, and CVD. Such
a strategy can also significantly reduce the need for lipidoptimizing drugs. Since meat contains one-third MUFA and
one-third cholesterol–neutral stearic acid, its consumption
can also be incorporated into a healthy diet, provided lean
cuts are used, and the quantity limited to 150 g/day.6
Practical recommendations on diet are given in Table 12.
Table 11. Summary of current knowledge on diet
• Quality of fat is more important than the quantity of fat consumed.
• SAFA is the principal determinant of elevated LDL levels. Reduction in energy intake from SAFA is the cornerstone of dietary
modification. Dairy products provide more SAFA than meat, even in western diets.
• Contrary to common belief, MUFA and PUFA can significantly lower LDL levels. Replacement of 20% of energy from SAFA with
MUFA or PUFA decreases TC level by 40 mg/dl.
• The atherogenicity and thrombogenicity of tropical oils are several times higher than meat.
• Increase in LDL level from lean meat is no higher than chicken, and need not be eliminated from a healthy diet.
• n-3 PUFA found in fatty fish is antithrombotic, antiarrhythmic, and prevents sudden death.
• The adverse effects from TRAFA consumption are greater than those from SAFA, because of increase in LDL and Lp(a) levels, and
decrease in HDL level.
• Both quality (glycemic index) and quantity (glycemic load) of carbohydrates are important determinants of insulin resistance and
the metabolic syndrome. A high glycemic index or load portends an inferior quality of carbohydrates.
• Although carbohydrates do not raise LDL levels, a high glycemic load is the major determinant of postprandial lipemia.
• Vegetarian diet is unhealthy if it contains large amounts of SAFA and TRAFA.
• Nuts, fruits, vegetables and whole grains can each reduce the risk of CVD by 15%–45%.
• Nuts are wholesome and nutritious food.
• The risk from alcohol outweighs the benefit in men <45 years and women <55 years of age.
• Drinking coffee does not increase the risk of heart disease but consumption of large amounts of unfiltered coffee can increase TC
levels.
• Tea is rich in antioxidants and flavonoids, and is associated with a reduced risk of CAD; however, most of the beneficial effects are
neutralized with the addition of milk.
• A calorie is a calorie, whether derived from carbohydrates, protein or fat.
• Obesity is a reflection of overnutrition (caloric excess), and a major cause of dyslipidemia.
• Caloric excess, irrespective of the composition of food, can raise LDL and lower HDL levels as a secondary effect of obesity.
• Weight reduction seen in high protein diets is due to the involuntary caloric restriction from the monotony of the diet rather than
the diet composition.
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328 Enas et al. Prudent Diet and Preventive Nutrition
Indian Heart J 2003; 55: 310–338
Table 12. Dietary recommendations
• A minimum carbohydrate intake of 100 g/day is necessary but should not exceed more than 300 g/day.
• Indians with or predisposed to the metabolic syndrome and diabetes should limit carbohydrate intake to <50% of energy.
• Most carbohydrate calories should be from whole grains and low glycemic index foods. A total fat intake of 30%–35% is preferable
to a very high carbohydrate diet.
• Reduce SAFA intake to <7% of the daily energy (10 g for women and 15 g for men), and cholesterol intake to <200 mg/day.
• Substitute excess SAFA and carbohydrate calories with MUFA (≤20%) and PUFA (≤10%).
• Substitute full-fat with low-fat milk and dairy products.
• Choose lean meat or skinless poultry, and limit the amount to <150 g/day.
• Minimize the intake of TRAFA by avoiding fried or crispy foods.
• Use cooking oils with beneficial effects on lipids and avoid deep-frying, especially with previously used oils.
• Consume 2–3 fish meals (200–300 g) per week; avoid frying to maintain the benefits.
• Those who are unable to consume fish may take the equivalent of 1g/day of EPA and DHA (3g of fish oil); 2 g/day is needed for
those with heart disease or high TG.
• Protein intake, up to 25% of energy, is permissible if most of the protein is from plant sources.
• Control caloric intake to achieve and maintain optimum weight and waistline.
• Increase physical activity to >60 min every day.
• Reduce intake of salt to <6 g/day.
• Eat a variety of foods, including whole grains, nuts, legumes, fruits, and vegetables.
• Consume nuts, up to 60 g/day, as a substitute for unhealthy foods.
• Increase intake of fruits to >5 servings/day (500 g/day), and use whole fruits instead of juices.
• Increase intake of vegetables to >5 servings/day (500 g/day), and avoid prolonged cooking of vegetables.
• Limit alcohol intake to 1–6 drinks/week.
Conclusions
People eat specific foods because of their taste, easy
availability and affordability, but are often unaware of the
health benefits and risks. Dietary modifications remain the
cornerstone of both the treatment and prevention of
diabetes and CVD, the twin epidemics of the twenty-first
century.234,388–391 A prudent diet together with regular
physical activity, avoidance of smoking, and maintenance
of a healthy body weight may prevent the majority of
diabetes and CVD in the Indian population.30 Aggressive
dietary interventions may reduce CVD events to a similar
magnitude as that achieved with statins. Compared with
medical or surgical interventions, nutritional intervention
is low-risk, low-cost, and readily available.259 A variety of
whole grains, not refined grains, as well as various types of
fruits and vegetables should be the main form of
carbohydrates.242 Prolonged cooking of vegetables should
be avoided. It is important to realize that the vegetarian diet
is healthy only when it is low in SAFA, and the predominant
energy is from foods with a low glycemic index.215 The best
way to counter the perils of contaminated vegetarianism
is by substituting full-fat dairy products with low-fat dairy
products. Cooking oils containing high SAFA should be
replaced with those containing high MUFA. Deep-frying,
especially with previously used oils, should be discouraged.
Nuts are healthy, wholesome foods, and their use should
be encouraged as a replacement for unhealthy calories.
IHJ-584-03.p65
328
A diet rich in fish has multiple benefits, including raising
HDL, and lowering TG levels, and preventing sudden
death.383 Consumption of fish is preferable to taking a large
number of fish oil capsules. There is increasing evidence
that dietary and lifestyle modifications begun in childhood
are likely to have benefits later in life.392 Therefore, these
dietary guidelines are applicable to all Asian Indians >2
years of age, and not just those with diabetes or heart
disease.
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Indian Heart J 2003; 55: 339–343
Lateef et al. Displacement of the Precordial Original
Leads and ECG
339
Article
Vertical Displacement of the Precordial Leads Alters
Electrocardiographic Morphology
Fatimah Lateef, Narayan Nimbkar, Zhuang Kun Da, Foo Rui Min
Department of Emergency Medicine, Singapore General Hospital, Singapore,
Uniformed Services University of Health Sciences Bethesda, Maryland, USA; National University of Singapore
Background: The present study was undertaken to assess whether the vertical displacement of electrodes
affects the waveforms of precordial leads.
Methods and Results: Two hundred forty healthy, adult volunteers had a standard 12-lead electrocardiogram,
a 12-lead electrocardiogram with the precordial leads displaced 2 cm cranially, and another with the precordial
leads displaced 2 cm caudally from the standard positions. All the three sets of electrocardiograms were visually
compared, and changes noted. One hundred twenty male and 120 female volunteers, 20–68 years of age, were
analyzed. Fifty-four males (45.0%) and 2 females (1.7%) showed no difference between the 3 sets of
electrocardiograms, while 66 males (55.0%) and 118 females (98.3%) had some changes. R wave amplitude
changes were noted in 63 male (52.5%) and 111 female (92.5%) volunteers; S wave amplitude changes were
seen in 59 males (49.2%) and 99 females (82.5%); T wave changes in 5 males (4.2%) and 3 females (2.5%); ST
segment changes in 1 male (0.8%) and none of the females; and QRS morphologic changes in 1 male (0.8%)
and 12 females (10.0%).
Conclusions: Precordial electrocardiographic waveform changes were seen with the vertical displacement of
the precordial leads. This will have implications on the interpretation of serial electrocardiograms. Healthcare
providers should take into consideration this deviation when interpreting serial ECGs. (Indian Heart J 2003;
55: 339–343)
Key Words: Electrocardiography, Precordial leads, Lead placement
E
lectrocardiography (ECG), introduced by Einthoven in
1902, is the graphical display of electrical potential
differences of an electric field originating in the heart and
recorded on the body surface. It represents a unique
technology that is safe, simple, and reproducible.1 Accurate
ECG interpretation assumes that technical standards are
adhered to during the acquisition and recording of tracings.
A number of technical factors may alter the quality of
recorded ECG. Some of these are patient-related, some are
operator dependent, and others relate to the equipment
utilized for recording.2
The exact placement of electrodes for ECG depends on
the interpretation and skill of the person performing it (e.g.
nurses, technicians, medical students). Placement of
precordial electrodes for the recording of a 12-lead ECG is
subject to variation. Technical variability represents the
largest source of error for variations in the amplitude and
Correspondence: Fatimah Lateef, Department of Emergency Medicine,
Singapore General Hospital, Outram Road, Singapore 169608.
e-mail: [email protected]
IHJ-455-03.p65
339
waveform of the chest lead ECG. Precordial leads are
commonly placed either too high, too low or horizontally
displaced from their anatomically defined sites. Persons
recording ECGs should ensure that the chest leads are
placed in the proper positions, and electrodes have good skin
contact to minimize artefacts. Incorrect placement may
lead to false diagnosis of infarction or cause alterations in
the ECG interpretation.3,4 In practice, the effect of the
displacement on individual ECGs is unknown.
The present study was done to assess if vertical
displacement of electrodes affects the waveform of
precordial leads of the ECG in healthy adult volunteers.
Methods
This was a clinical experimental investigation. Following
ECGs in supine position were performed in healthy, adult
volunteers, with no history of ischemic heart disease (IHD).
(i)
a standard 12-lead ECG with the usual accepted,
surface precordial lead placement;
11/19/2003, 11:24 PM
340 Lateef et al. Displacement of the Precordial Leads and ECG
(ii) a 12-lead ECG, as in (i), but with all the precordial leads
(i.e. V1 to V6) shifted 2.0 cm cranially; and
(iii) a 12-lead ECG as in (i), but with all the precordial leads
shifted 2.0 cm caudally.
Measurements were done with a standard ruler. All the
three ECGs for each volunteer were visually compared, and
the differences documented (e.g. R and S wave amplitude
changes, changes in the QRS morphology, ST segment
changes, T wave morphology and appearance/
disappearance of Q waves). T wave changes refer to either
an upright, inverted or flattened T wave. ST segment
changes may represent an isoelectric ST segment, or ST
elevation, or depression. The morphological changes would
refer to changes such as the appearance of a bundle branch
block pattern.
The standard 12-lead ECG for each person was used as
the control against which the other two ECGs, which had
deliberate alterations in the positions of the precordial leads,
were compared. When the tracings with the displaced
electrodes did not resemble the standard ECG tracings, the
variations were confirmed by repeating the tracings.
The study was approved by the hospital ethics
committee.
Indian Heart J 2003; 55: 339–343
Fig. 1a. Normal position: amplitude of the R wave in V3 (+27 mm).
Fig. 1b. 2 cm cranial: amplitude of the R wave in V3 (+9 mm).
Results
There were a total of 240 volunteers, 20–68 years of age.
One hundred and twenty were males and 120 females.
Fifty-four males (45.0%) and 2 females (1.7%) showed no
differences when their three sets of ECGs were compared,
while 66 males (55.0%) and 118 females (98.3%) had some
changes noted. R wave amplitude changes were noted in
63 male (52.5%) and 111 female (92.5%) volunteers; S
wave changes in 59 males (49.2%) and 99 females (82.5%)
(Figs 1a–c); T wave changes in 5 males (4.2%) and 3 females
(2.5%) (Fig. 2a–c); ST segment changes in 1 male (0.8%)
and none of the females; and QRS morphological changes
in 1 male (0.8%) and 12 females (10.0%) (Figs 2a–e)
(Table 1). There was no Q wave appearance or
disappearance noted in the group studied. Table 1
demonstrates the confidence intervals at p=0.01.
R and S wave changes were mainly amplitude changes
(i.e. the height of the R wave and depth of the S wave). The
range of R wave amplitude change was from +3 mm to
+15 mm (positive indicates above the isoelectric baseline),
while that for S was –2 mm to –15 mm (negative indicates
below the isoelectric baseline) (Figs 1a–c). All the volunteers
who had S wave changes also had R wave changes.
Analysis of the changes showed that these were
commonest in leads V1, V2, and V3, irrespective of whether
the displacement was cranial or caudal (Tables 2 and 3).
IHJ-455-03.p65
340
Fig. 1c. 2 cm caudal: amplitude of the R wave in V3 (+10 mm).
Changes were not observed in the ramaining precordial
leads, namely leads V4, V5, and V6.
As the volunteers did not have any history of
cardiovascular problems, none of them presented with any
cardiorespiratory symptoms. There was one volunteer who
was detected to have left ventricular hypertrophy on ECG,
which was repeated for reconfirmation. She was
subsequently offered assessment by a cardiologist as an
outpatient.
Discussion
There are numerous potential clinical uses of the 12-lead
11/19/2003, 11:24 PM
Indian Heart J 2003; 55: 339–343
Lateef et al. Displacement of the Precordial Leads and ECG 341
Table 1. Changes observed when comparing the 3
electrocardiograms
Changes
observed
Number of
males (%)
Number of
females (%)
None
54 (45.0)
CI: 33.87–56.65
66 (55.0)
CI: 43.35–66.13
63 (52.5)
CI: 40.94–63.80
59 (49.2)
CI: 37.77–60.65
5 (4.2)
1 (0.8)
1 (0.8)
2 (1.7)
CI: 0.33–8.07
118 (98.3)
CI: 91.3–99.67
111 (92.5)
CI: 83.85–96.70
99 (82.5)
CI: 71.93–89.66
3 (2.5)
12 (10.0)
0
Changes
R wave amplitude
Fig. 2a. Normal position: QRS complex in V1 showing an RS pattern with T
wave inversion in V3.
S wave amplitude
T wave
QRS morphological
ST segment
CI: confidence interval
Note: Some patients had more than one category of change (e.g. patient
A had both R wave and S wave amplitude changes), therefore, the total
number of changes may be more than the number of volunteers.
For male volunteers, T wave, QRS morphology, and ST segment changes
when taken together, the CI at p=0.01 was 33.87%–56.65%.
For female volunteers, the CI at p=0.01 was 6.64%–22.29%.
Fig. 2b. 2 cm cranial: QRS complex in V1 showing an RSR' pattern with upright
T wave in V3.
Table 2. Detailed changes among male volunteers
Changes
Leads
Cranial
displacement
R wave
V1
V2
V3
6
29
42
9
34
38
S wave
V1
V2
V3
0
19
40
0
22
37
T wave
V1
V2
V3
0
3
3
1
1
3
QRS complex
V1
1
0
ST segment
V1
V2
V3
0
1
0
0
0
0
Fig. 2c. 2 cm caudal: QRS complex in V1 shows RS pattern with T wave
inversion in V3.
Fig. 2d. Enlargement of Fig. 2a (normal) V1: RS pattern
Fig. 2e. Enlargement of Fig. 2b (2cm cranial) V1: RSR' pattern
IHJ-455-03.p65
341
Caudal
displacement
Note: Some volunteers showed changes in more than one lead, and also
changes in either one or both of the cranial and caudal displacement leads.
For these reasons, the numbers may not tally, and may be more than the
total number of male volunteers.
ECG. The ECG may reflect changes associated with primary
and secondary myocardial processes, metabolic and
electrolyte abnormalities, as well as toxic or therapeutic
effects of drugs or devices. ECGs are composed of a number
of waveforms, each with its own sensitivity and specificity,
11/19/2003, 11:24 PM
342 Lateef et al. Displacement of the Precordial Leads and ECG
Table 3. Detailed changes among female volunteers
Changes
Leads
Cranial
displacement
Caudal
displacement
R wave
V1
V2
V3
4
56
71
0
46
73
S wave
V1
V2
V3
1
27
71
3
32
64
T wave
V1
V2
V3
1
1
1
0
2
1
QRS complex
V1
V2
V3
2
7
3
3
4
5
Note: Some volunteers showed changes in more than one lead, and also
changes in either one or both of the cranial and caudal displacement leads.
For these reasons, the numbers may not tally, and may be more than the
total number of female volunteers.
and each influenced by a variety of pathologic and
pathophysiologic factors. For example, although ST
segment and T wave changes are the commonest and most
sensitive, these changes are also the least specific.3–5
There is continuing uncertainty about standardized
procedures for the placement of ECG chest electrodes.
Technical variability represents the largest source of error
for short-term variations in amplitude and waveforms of
the chest lead ECG. There is uncertainty about locating the
mid-clavicular line and, thus, the position of V 4,
particularly in obese persons, and females. Appropriate
selection of the position for chest leads may help in
removing the inconsistencies in ECG interpretation and
selection criteria for therapy, thus improving comparability
of treatment results.6
Amplitude changes are not uncommon. Previous studies
on modified positions of the limb leads have shown
considerable amplitude and waveform changes in the
frontal plane ECG.7,8
The R wave (QRS complex) reflects the depolarization
phase of the ventricles. It has been shown that in those
with coronary artery disease/ischemic heart disease, there
is often poor progression of the R wave as one moves across
the precordial leads and approaches V6.9
As for extrasystoles, Michaelides et al.10 in a study using
angiographic confirmation, showed that the R wave of the
extrasystoles is positively correlated with the number of
obstructed coronary arteries, Barnhill et al.11 studied R and
S waves (terminal portion of the QRS complex) in patients
IHJ-455-03.p65
342
Indian Heart J 2003; 55: 339–343
with myocardial infarction (MI), and concluded that these
were commonly affected, and very sensitive to changes and
variations.
Feldman et al.,12 in a study that examined R wave
amplitude and left ventricle chamber size, concluded that
there is a direct and dynamic correlation between the two
factors. Chamber size and distance from the left ventricle
to leads V5 and V6 were major determinants of the R wave
amplitude. R and S wave amplitudes are also important in
diagnostic criteria such as left ventricular hypertrophy
(LVH).
The morphology of the ECG depicts the resultant
electrical vector in 3 dimensions, with time being the fourth
dimension. Hence, it is natural that the morphology of the
ECG is known to be affected by the position of the heart,
position of the unipolar leads in relation to the heart, as
well as the pathway between the heart and unipolar
electrodes. For example, with alteration in position of the
precordial electrodes, the current may have to pass through
a different, more circuitous route, if there is nonconductive
tissue encountered along the more direct pathway. Other
factors that have been shown to affect ECG morphology
include body position,13 and age.14 There have been some
studies on ethnicity, and its effect on ECGs.15–16 However,
most of these studies are small and may be applicable to
the local, ethnic population only.
It has often been thought that with changes in the
placement of leads, there will be ST segment alterations
affecting our interpretation of MI (i.e. ST segment
elevation), especially when comparing serial ECGs.17 In this
study, there was only one male patient (0.8%) in whom ST
segment change was noted. This assumption may not be
as common as previously thought.
There is intra-individual precordial voltage variation in
serial ECGs. It is necessary to improve reproducibility and
precision in the performance of ECGs. There is also a need
to emphasize how electrode placement is taught to nurses,
as well as their accountability for this duty.18,19
A new device known as the precordial ECG BELT, using
a 6-lead precordial application, has been used in studies to
compare its accuracy with standard precordial lead
application. Results have indicated disagreement between
the two methods.20 The most obvious weakness of the ECG
BELT was the inability to obtain a reading with a stable
baseline. The findings suggest that the ECG BELT is not
adequate for clinical application in its current form.20
Another alternative may be a device with less surface
connections, such as the EASI ECG. This device uses only 5
surface connections to derive the 12-lead ECG. Perhaps with
less connections, there would be less placement error and
11/19/2003, 11:24 PM
Indian Heart J 2003; 55: 339–343
Lateef et al. Displacement of the Precordial Leads and ECG 343
variations. The EASI system has been favorably compared
with the standard 12-lead ECG.
Therefore, to reduce inconsistencies, the practice of
marking precordial lead positions for short-term serial ECGs
should be encouraged. Physicians should also be more
cognizant of ECG changes caused by precordial lead
displacement when comparing serial ECGs.
This study has shown that variations do exist among
normal individuals. It is the first time this has been proven
objectively on normal individuals. This suggests the need
for standardization, or the use of a device to assist in lead
placement, which can ensure accuracy, reproducibility, and
objectivity.
References
1. Einthoven W. [Weiteresinber das elektrokardiogramm]. Arch Gesamte
Physiol 1908; 172: 517–520
2. Fisch C. Evolution of the clinical electrocardiogram. J Am Coll Cardiol
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3. Friedberg CK, Zager A. “Non-specific” ST and T wave changes. Clin
All Round 1961; 23: 655–661
4. Hurst JW. Images in cardiovascular medicine. “Switched” precordial
leads. Circulation 2000; 101: 2870–2871
5. Kadish AH, Buxton AE, Kennedy HL, Knight BP, Mason JW, Schuger
CD, et al. ACC/AHA clinical competence statement on electrocardiography and ambulatory electrocardiography. A report of
the ACC/AHA/ACP-ASIM Task Force on Clinical Competence
(ACC/AHA Committee to Develop a Clinical Competence Statement
on Electrocardiography and Ambulatory Electrocardiography).
J Am Coll Cardiol 2001; 38: 2091–2100
6. Rautaharju PM, Park L, Rautaharju FS, Crow R. A standardized
procedure for locating and documenting ECG chest electrode
positions: consideration of the effect of breast tissue on ECG
amplitudes in women. J Electrocardiol 1998; 31: 17–29
7. Rautaharju PM, Prineas RJ, Crow RS, Seale D, Furberg C. The effect
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Takuma K, Hori S, Sasaki J, Shinozawa Y, Yoshikawa T, Hand S, et al.
An alternative limb lead system for electrocardiographs in emergency
patients. Am J Emerg Med 1995; 13: 514–517
Chia BL. Ischaemic heart disease. In: Clinical electrocardiography.
3rd ed. World Scientific Publishers. pp. 11-37
Michaelides AP, Vyssoulis GP, Paraskevas PG, Skouros CG, Tsiamis
EG, Toutouzas PK. Significance of R wave changes in exerciseinduced supraventricular extrasystoles. Angiographic correlates. J
Electrocardiol 1993; 26: 197–206
Barnhill JE 3rd, Tendera M, Cade H, Campbell WB, Smith RF.
Depolarization changes early in the course of myocardial infarction:
significance of changes in the terminal portion of the QRS complex.
J Am Coll Cardiol 1989; 14: 143–149
Feldman T, Borow RM, Neumann A, Lang RM, Childers RW. Relation
of electrocardiographic R-wave amplitude to changes in left
ventricular chamber size and position in normal subjects. Am J Cardiol
1985; 55: 1168–1174
Adams MG, Drew BJ. Body position effects on the ECG: implications
for ischemia monitoring. J Electrocardiol 1997; 30: 285–291
Bachman S, Sparrow D, Smith LK. Effects of aging on the
electrocardiogram. Am J Cardiol 1981; 48: 513–516
Mansi IA, Nash IS. Ethnic differences in the ST segment of the
electrocardiogram: a comparative study among six ethnic groups.
Am J Emerg Med 2001; 19: 541–554
Chen CY, Chiang BN, Macfarlane PW. Normal limits of the
electrocardiogram in a Chinese population. J Electrocardiol 1989; 22:
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Herman MV, Ingram DA, Levy JA, Cook JR, Athans RJ. Variability of
electrocardiographic precordial lead placement: a method to improve
accuracy and reliability. Clin Cardiol 1991; 14: 469–476
Bupp JE, Dunger M, Lawrence C, Wingate S. Placement of cardiac
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McConnell EA. Applying cardiac monitor electrodes. Nursing 1998;
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Bell SJ, Clifton J, Pease J, Greenfield JC, Leggett S, Maynard C, et al:
The evaluation of a precordial ECG BELT: technologist satisfaction
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11/19/2003, 11:24 PM
344 Shrivastava
et al.
Original
Article
Coronary Calcium and CAD
Indian Heart J 2003; 55: 344–348
Coronary Calcium and Coronary Artery Disease:
An Indian Perspective
Sameer Shrivastava, Vinayak Agrawal, Ravi R Kasliwal, Dhanraj R Jangid,
Ashok Sen, Atul Verma, Naresh Trehan
Departments of Cardiology and Nuclear Medicine, Escorts Heart Institute and Research Centre, New Delhi
Background: Coronary artery calcification is a part of the development of atherosclerosis. It occurs exclusively
in atherosclerotic arteries and can be used as a noninvasive marker of coronary atherosclerosis. As there is no
large-scale study on coronary calcium score reported in the Indian population till date, this study was undertaken
for calculating the score in Indians at intermediate-to-high risk of coronary artery disease, and to correlate it
with angiographically proven coronary artery disease.
Methods and Results: A total of 388 consecutive patients who underwent coronary calcium scoring and
coronary angiography were included in the study. Calcium scoring was performed based on a modification of
the Agatston Score using a high-speed computed tomography scanner (GE® CT/i scanner). Coronary calcium
scores were correlated with the presence or absence of significant coronary artery disease (defined as ≥70%
stenosis of at least one major epicardial coronary artery) on angiography. Out of 388 patients who underwent
coronary angiography, 298 were found to have significant coronary artery disease. Mean coronary calcium
score was significantly higher in patients with angiographically proven coronary artery disease (226.7±65.2)
as compared to those who had normal angiograms (20.29±56.7; p value<0.0001). All the 72 patients who
had a score >400 had an abnormal angiogram (sensitivity 23.1%, specificity 100%, positive predictive value
100%, and negative predictive value 24.1%). On the other hand, among the patients who had a score >0, 298
were found to have abnormal angiograms, while 16 had normal angiograms (sensitivity 95.5%, specificity
78.9%, positive predictive value 94.9%, and negative predictive value 81.1%).
Conclusions: Detection of coronary calcium score by a helical computed tomography scanner is a useful tool
for predicting the presence of significant coronary artery disease in intermediate-to-high risk patients. An
absolute score of 0 has a high negative predictive value for the presence of coronary artery disease, and may
obviate the need to perform coronary angiogram in intermediate-risk patients. On the other extreme, score
>400 is highly predictive of the presence of coronary artery disease, and virtually confirms the presence of
significant coronary artery disease in intermediate-to-high risk patients. (Indian Heart J 2003; 55:
344–348)
Key Words: Coronary artery disease, Coronary calcium score, Computed tomography
C
alcification is closely associated with atheromatous
plaque, and is a recognized marker for coronary artery
disease.1 Until recently, it was believed that calcium present
in the atheromatous plaques is in the form of calcium
phosphate, precipitated in a passive manner. However,
recent findings indicate that calcification is an active
process and calcium is deposited as hydroxyapatite, similar
to that in active bone formation.2 It is known that the
amount of calcium in the coronary arteries is better
Correspondence: Dr Vinayak Agrawal, 103, Siddhartha Enclave, New
Delhi. e-mail: [email protected]
IHJ-478-03.p65
344
correlated with the amount of atherosclerosis in different
individuals and, to a lesser extent, with the segments of
the coronary tree in the same individual. It is not known
whether the quantity of calcium tracks the quantity of
atherosclerosis over time in the same individual. There are
numerous articles on the correlation of coronary calcium
with angiographically proven coronary artery disease
(CAD); however, there are no such large studies from India.
This study was aimed at using helical computed
tomography (CT) scan for calculating coronary calcium
scores (CCSs) in the Indian population.
11/19/2003, 11:25 PM
Indian Heart J 2003; 55: 344–348
Methods
The study included 388 consecutive patients who
underwent coronary calcium scoring as well as coronary
angiography. These included patients who had presented
with either typical symptoms suggestive of ischemic heart
disease (with or without a positive stress test), or atypical
symptoms with a positive stress test for reversible
myocardial ischemia, putting these patients into a pretest
probability of intermediate-to-high risk category. All the
patients underwent detailed clinical evaluation,
biochemical tests, coronary calcium scoring, and coronary
angiography. Biochemical tests included fasting and postprandial blood sugar, and fasting lipid profile.
Assessement of CCSs was done by using a high-speed
CT scanner (GE® CT/i scanner). Scores were computer
generated using an advanced software “smart-score
calcium” adapting a modification based on Agatston Score.
Total CCSs thus obtained were correlated with the presence
or absence of significant CAD. Significant CAD was defined
as ≥70% stenosis of at least one of the major epicardial
coronary arteries on coronary angiography. Informed
consent was obtained from the entire patient population
enrolled in the study. The study was approved by the
hospital ethics committee.
Statistical analysis : The data obtained were maintained
on a Microsoft excel spreadsheet. The differences in various
parameters between the different groups were assessed by
using Chi-square and t tests, as indicated. Sensitivity,
specificity, positive predictive value (PPV), and negative
predictive value (NPV) for different risk scores were
calculated. A p value <0.05 was considered significant. All
the statistical analyses were done on SPSS 10.0 for
Windows.
Results
A total of 388 consecutive patients underwent coronary
calcium scoring and coronary angiograms to rule out
significant CAD. Three hundred twenty-five patients
(83.8%) were male while 63 (16.2%) were female. The
mean age of the patients was 52.3±11.3 years (range 15–
78 years). Out of these patients, 76.2% were less than 60
years of age, and 23.8% were more than 60 years of age.
For the purpose of analysis, patients were divided into four
groups according to CCS: 0, 1–100, 101–400, and >400.
There was no statistically significant difference in the
prevalence of various conventional cardiovascular risk
factors in different calcium score groups (Tables 1 and 2).
The presence or absence of significant CAD on coronary
IHJ-478-03.p65
345
Shrivastava et al. Coronary Calcium and CAD 345
angiography in different calcium score groups is presented
in Table 3. Sensitivity, specificity, PPV, and NPV for the
prediction of significant CAD were calculated for three
different calcium scores, namely >0, >100, and >400
(Table 4). All the 72 patients who had CCSs >400 had
abnormal angiograms, yielding a sensitivity of 23.1%,
specificity 100%, PPV 100%, and NPV 24.1%. Two
hundred thirty-six patients with CCS>100 had abnormal
angiograms, with only 4 patients having normal
angiogram (sensitivity 75.6%, specificity 94.7%, PPV
98.3%, and NPV 51.3%). Out of 314 patients who had
Table 1. Incidence of various risk factors in relation to the
calcium score
Risk factor
Calcium score
≤100
(n=148)
101–400
(n=168)
p value
>400
(n=72)
Age (years)
47.2±10.7 51.3±10.6 49.2±10.1
Male (%)
86.5
80.4
86.1
Hypertension (%) 12.5
11.1
14.7
Diabetes (%)
3.8
5.6
8.8
Family history (%) 11.5
11.1
8.8
Smoking (%)
5.4
3.7
2.9
ns
ns
ns
ns
ns
ns
ns: not statistically significant
Table 2. Correlation of calcium score with lipid profile
Lipid profile (mg/dl)
Total cholesterol
Triglycerides
High-density
lipoproteins
Low-density
lipoproteins
Very low-density
lipoprotein
Calcium score
p value
≤100
(n=148)
101–400
(n=168)
>400
(n=72)
204±45
220±47
42±11
220±57
181±41
44±9
216±10
129±33
41±13
ns
ns
ns
125±37
142±47
140±18
ns
40±9
34±8
25±7
ns
ns: not statistically significant
Table 3. Coronary calcium score correlation with coronary
angiography findings
>400
(n=72)
Abnormal angiogram 72
Normal angiogram
0
11/19/2003, 11:25 PM
Calcium scores
101–400 1–100
(n=168) (n=74)
164
4
62
12
0
(n=74)
14
60
Indian Heart J 2003; 55: 344–348
346 Shrivastava et al. Coronary Calcium and CAD
Table 4. Sensitivity, specificity, positive predictive value,
and negative predictive value of different calcium scores
for predicting the presence or absence of significant
coronary artery disease
Calcium scores
Sensitivity
Specificity
Positive predictive value
Negative predictive value
>400
>100
0
23.1
100
100
24.1
75.6
94.7
98.3
51.3
95.5
78.9
94.9
81.1
Zero Calcium Socre
High Calcium Socre
Fig. 1. Normal and high calcium score images.
CCSs >0, 298 were found to have abnormal angiograms
while 16 patients had normal angiograms (sensitivity
95.5%, specificity 78.9%, PPV 94.9%, and NPV 81.1%).
Discussion
Quantification of calcium in the coronary arteries has been
shown to reflect the total atherosclerotic plaque burden.3,4
This quantification can be determined in a straightforward
manner by using advanced high-speed CT scans including
helical CT scans, multi-slice CT scans, and electron-beam
CT (EBCT) scans. In several studies, detection and
quantification of coronary artery calcification with EBCT
in suspected CAD patients has been compared with widely
available conventional helical CT scan. Although images
of the heart from conventional CT scans may suffer from
cardiac motion artifacts, calcium scoring with spiral or
multi-slice CT scanners has the potential to identify patients
with CAD with an accuracy similar to that of EBCT scan.5–7
Protocols with prospective or retrospective electrocardiography triggering can be used, which appear to yield results
similar to Agatston CCS with EBCT scans, despite technical
differences.8
Calcification is not found in normal coronary arteries.
The atherosclerotic process starts in the second decade of
life, when calcium deposition begins. The calcium
deposition increases with age, and with progression of
atherosclerotic lesions. Coronary artery calcification is
temporally related to vascular inflammation and the demise
of lipid-laden macrophages.9,10 The exact mechanism is
unclear, and may be due to the deposition of extracellular
calcium from dying cells, or the formation of bone-like
structure by calcifying cells.11,12 Since calcium is deposited
only in the atherosclerotic plaques and not in the normal
vessels, and since atherosclerosis is a diffuse process, a high
coronary calcium burden reflects the presence of more
extensive coronary atherosclerosis (Fig. 1). Hence, higher
CCSs are associated with the presence of significant CAD
IHJ-478-03.p65
346
and future risk of adverse coronary events. Moreover,
contrary to popular belief, coronary calcium deposition
may represent a type of plaque instability, namely plaque
rupture. It was earlier believed that calcified areas are
unlikely to be associated with the sites of plaque rupture.13
However, the stiffened calcific area can induce stress at the
junction of the calcified and noncalcified sections, which
is a common site of plaque rupture.14 Burke et al.15 found
that, contrary to expectations, the degree of calcification
was greatest for acute and healed plaque ruptures, and least
for plaque erosion. It has been suggested that the presence
of calcium within a heterogeneous, fat-laden plaque
renders the plaque more susceptible to stress cracking, as
compared to a plaque that contains no calcium.16
However, calcium deposition as detected by coronary
calcium scoring does not correlate with the site and severity
of luminal narrowing on coronary angiography. The
observation that coronary plaque burden is poorly
correlated with luminal narrowing has been confirmed by
studies using intravascular ultrasound (IVUS), and can be
explained by the process of vascular remodeling.17–19 As the
atherosclerotic plaque accumulates in the coronary artery
wall, there is an outward remodeling leading to the
preservation of luminal size.20 However, the likelihood of
plaque rupture leading to acute MI is not decreased and
may even be increased. Thus, the apparent lower specificity
of CCS for angiographic obstruction in some studies may
in fact be due to the inability of angiography to detect
extraluminal plaque.21 However, an increased CCS would
mean the likelihood of significant CAD elsewhere or at
another site.
Our data also suggest that in symptomatic patients, the
mere presence of calcium is a very sensitive index for the
presence of significant CAD somewhere in the coronary
arteries. Any CCS >0 has a high sensitivity and reasonably
good specificity, with good PPV to predict the presence of
obstructive CAD. There have been numerous studies that
11/19/2003, 11:25 PM
Indian Heart J 2003; 55: 344–348
have proved coronary calcium scoring to be an excellent
predictor of the presence of angiographically proven
obstructive CAD, and future risk of adverse cardiovascular
events. In a large study conducted by Budoff et al.22 in 710
symptomatic subjects with a mean age of 56 years,
comparing EBCT scan with coronary angiography, the
sensitivity, specificity, and NPV were 95%, 44%, and 84%,
respectively. Breen et al. 23 and Kaufmann et al. 24
demonstrated the relationship between CCS and coronary
artery lumen obstruction as assessed by coronary
angiography. Kaufmann et al.24 studied 160 symptomatic
individuals 23–59 years of age and compared CCS with
coronary artery stenosis. Sensitivity, specificity, and accuracy
ranged from 81% to 86%. Several other groups25–30 have
confirmed the association of increased CCS with increased
presence and severity of CAD.
He et al.31 studied nearly 400 asymptomatic patients
using EBCT scan and SPECT, and showed that none of the
patients with a CCS <10 had an abnormal SPECT. Out of
of these, 2.6% of patients with CCS 10–100, 11.3% with
a CCS of 101–399, and 46% with CCS>400 had a SPECT
showing ischemia. This high sensitivity and low specificity
probably relates to the fact that only 20% of the
atherosclerotic plaque is calcified. However, the absence of
calcification seems to indicate a lack of significant luminal
stenosis.
In the Rotterdam Coronary Calcification Study,32 a
strong and graded association was found between coronary
calcification and MI. In a similar study of patients with
suspected CAD, CT scan showed a 65% sensitivity, and 87%
specificity for coronary artery calcification.33 According to
the American Heart Association Expert Consensus
document on the use of EBCT for the diagnosis and
prognosis of CAD,34 a meta-analysis of the relationship
between CAD and calcium prevalence in patients
undergoing EBCT and cardiac catheterization to determine
the diagnostic accuracy of EBCT in catheterized patients
demonstrated a high sensitivity of EBCT for CAD, a much
lower specificity and an overall predictive accuracy of 70%
in typical CAD patient populations. The test has proven to
have a predictive accuracy approximately equivalent to the
alternative methods for diagnosing CAD, but was not found
to be superior to alternative noninvasive tests such as SPECT
imaging. A positive calcium score might be valuable in
determining whether a patient who appears to be at
intermediate risk of CAD is actually at high risk. Conversely,
a low or absent calcium score may also prove useful in
determining a low likelihood of developing CAD. The
absence of coronary calcification identifies patients with
false-positive exercise treadmill testing, and the two can be
IHJ-478-03.p65
347
Shrivastava et al. Coronary Calcium and CAD 347
combined to obtain complementary information. 35 A
negative (<0) calcification generally excludes obstructive
CAD. Hence, this technique can be used to evaluate patients
with atypical chest pain. If the CCS is zero, the source of
pain is unlikely to be due to CAD. If the CCS is very high
(>400), the chances of the presence of obstructive CAD
are steep.
Since coronary calcium scoring is a screening tool, a
technique that has a very high sensitivity for the prediction
of obstructive CAD is desirable. In our study, which involved
intermediate-to-high risk patients, a CCS >0 had a very
high sensitivity for obstructive CAD with fairly high
specificity. There was a progressive increase in PPV with
increasing CCS, suggesting that high CCSs are increasingly
associated with obstructive CAD. Thus, a CCS of zero may
be used to obviate the need for coronary angiography in
intermediate-risk patients and in selected high-risk patients,
when coronary angiography is not the preferred method
due to concomitant co-morbid conditions (such as renal
dysfunction, terminal illnesses, etc.). In such patients, a
high CCS, particularly >400, virtually confirms the
presence of significant CAD, and can help in devising
further management strategies.
Limitations: Our study suffered from certain limitations.
It involved only those individuals who were at intermediateto-high risk of having significant CAD. Patients at low risk
of CAD could not be included because of obvious ethical
reasons. Hence, there was a definite selection bias that could
not have been avoided.
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Indian Heart J 2003; 55: 349–353
Malhotra et al. Prehospital Delay in Treatment
of AMI
349
Original
Article
Prehospital Delay in Patients Hospitalized With
Acute Myocardial Infarction in the Emergency Unit of a
North Indian Tertiary Care Hospital
S Malhotra, M Gupta, KK Chandra, A Grover, P Pandhi
Departments of Pharmacology and Cardiology, Post Graduate Institute of Medical Education and Research, Chandigarh
Background: Prompt treatment of patients presenting with acute myocardial infarction decreases the incidence
of death from early arrhythmia, and maximizes the potential benefit of thrombolytic therapy. Prehospital delay
has been identified as a major obstacle to the widespread use of thrombolytic therapy. The aim of the present
study was to examine the extent of, and factors associated with, delay in seeking medical care (usually
thrombolytic therapy) in patients with acute myocardial infarction.
Methods and Results: The study was conducted in patients visiting the medical emergency unit of the Nehru
Hospital, Post Graduate Institute of Medical Education and Research, Chandigarh. A total of 104 patients
diagnosed with acute myocardial infarction were interviewed using a pre-designed proforma. Pain-to-door, and
door-to-drug times, were the main outcome measures. The corrected mean (SEM) and median (range) pain-todoor times were 8.5 (0.8) hours and 5.2 (0.5–24) hours, respectively. Out of 104 patients, 38 did not receive
thrombolytic therapy. In those who did not receive thrombolytic therapy, prior therapy at local health centers,
lack of knowledge of symptoms, and transportation problems were the main reasons for hospital delay. The
mean (SEM) and median (range) of door-to-drug times were 1.2 (0.1) hours and 1 (0.2–3.5) hours, respectively.
(Indian Heart J 2003; 55: 349–353)
Key Words: Prehospital delay, Thrombolytic therapy, Acute myocardial infarction
A
cute myocardial infarction (AMI) results from
prolonged myocardial ischemia, precipitated in most
cases by an occlusive coronary thrombus at the site of a
pre-existing atherosclerotic plaque. It is a major cause of
mortality and morbidity in the general population.
Currently, the prevalence of coronary artery disease (CAD)
in the age group of 40–50 years in urban India is 4-fold
higher than in the United States1 (10% v. 2.5%).
Numerous studies have demonstrated the benefits of
thrombolytic therapy for patients with evolving AMI.2 Thus
attention has shifted towards efforts to increase the use of
this therapy. However, the benefits of thrombolytic therapy
are greater in the first few hours after the onset of
symptoms. 3 Hence, patient-associated delay in the
recognition of symptoms of heart attack has been identified
as a major obstacle to the widespread use of thrombolytic
therapy.4 The duration of prehospital delay includes the
Correspondence: Dr (Mrs) P Pandhi, Department of Pharmacology, Post
Graduate Institute of Medical Education and Research, Chandigarh 160012.
e-mail: [email protected]
IHJ-470-03.p65
349
time required to recognize the symptoms, decision to seek
care, arrange transportation, travel to the hospital, and the
time required for diagnosis.5
A large number of factors have been attributed to
prehospital delay; these include sociodemographic,
behavioral, clinical, and situational constraints.6 The aim
of the present study was to examine the extent of, and
factors associated with, delay in seeking medical care
(usually thrombolytic therapy) in patients with AMI.
Methods
The study was conducted in patients presenting with AMI
admitted to the medical emergency or coronary care unit
of the Nehru Hospital, Post Graduate Institute of Medical
Education and Research, Chandigarh from December 2001
to June 2002. One hundred four consecutive patients of
MI were interviewed using a pre-designed proforma. The
chief constituents of the questionnaire included the
demographic characteristics of the patient, nature and time
of onset of symptoms, pre-existing illness and treatment
11/19/2003, 11:25 PM
350 Malhotra et al. Prehospital Delay in Treatment of AMI
received, and any previous knowledge about symptoms of
heart attack. The patients were then asked about the time
at which they presented to the emergency unit and received
medical care. The main outcome measures included: (i)
pain-to-door time (time interval between the onset of
symptoms suggestive of AMI and arrival in the emergency
unit); and (ii) door-to-drug time (time interval between
arrival in the emergency unit and administration of
thrombolytic therapy).
Indian Heart J 2003; 55: 349–353
Pain–door–drug times: The mean (SEM) and median
(range) pain-to-door times were 13 (2.1) hours and 5.2
(0.5–12) hours, respectively. The corrected (delay equals
24 hours for those delaying 24 hours or more) mean (SEM),
and median (range) pain-to-door times were 8.5 (0.8) hours
and 5.2 (0.5–24) hours, respectively (Fig. 2).
Statistical analysis: The data were expressed as mean
(±SEM) and median. To examine the differences between
different delay groups for continuous variables, t tests and
analysis of variance (ANOVA) were used. A value of p<0.05
was considered statistically significant.
Results
Prehospital delay [corrected mean (SEM) hours]
Of the 104 consecutive MI patients studied, 66 received
thrombolytic therapy. We initially examined the association
between demographic and clinical factors, and duration
of prehospital delay (Table 1). The average and median
delay times increased with advancing age. Men did not
experience significant delay as compared to women. Also,
delay was not significant in patients with respect to the
location and type of MI. Patients with a history of angina
exhibited prolonged delay compared with patients without
angina (13.4 v. 3.2 hours). However, patients with a
history of diabetes and hypertension did not experience
significant delays as compared with patients without these
conditions. Patients seeking treatment from local
physicians delayed longer than those who came
straightaway to the emergency unit (16.1 v. 6 hours) (Fig.
1). We also found that patients who did not know the
symptoms of heart attack delayed longer than those who
had a good knowledge (Fig. 1).
The mean (SEM) and median (range) of door-to-drug
times were 1.2 (0.1) hours and 1 (0.2–3.5) hours,
respectively (Table 2).
Prehospital delay was the cause for 30 of the 38 patients
(79%) not receiving any thrombolytic therapy. In the
remaining 8 patients, the causes for not receiving
thrombolysis were: unaffordability of urokinase (3),
unaffordability of streptokinase (1), associated
contraindications for thrombolysis (2), and already received
thrombolysis (2) (Fig. 3). Prior therapy at local healthcare
services, lack of knowledge of symptoms, and
transportation problems were the main reasons for
prehospital delay in nonthrombolyzed patients.
Prehospital delay
Unaffordability of urokinase
Unaffordability of streptokinase
Associated contraindications for
thrombolysis
Already thrombolized
Prior local treatment
None
Treatment color
No
Yes
Knowledge of disease symptoms
Fig. 1. Effect of treatment order and patients’ knowledge of disease symptoms
on prehospital delay.
IHJ-470-03.p65
Fig. 2. Prevalence of prehospital delay (pain-to-door time in patients with acute
myocardial infarction).
350
Fig. 3. Reasons for not receiving thrombolytic therapy.
11/19/2003, 11:25 PM
Indian Heart J 2003; 55: 349–353
Malhotra et al. Prehospital Delay in Treatment of AMI 351
Table 1. Demographic and clinical characteristics associated with prehospital delay
Delay time (hours)
Factor
Age (years)
<35
35–44
45–54
55–64
65–74
>75
Sex
Male
Female
AMI order
Initial
Prior
AMI location
Anterior and /or
lateral
Inferior or
posterior
Day of the week
Weekend
Weekday
Time of the day
6:00–11:59 am
Noon–5:59 pm
6:00–11:59 pm
Midnight
Pain
Present
Absent
Dyspnea
Present
Absent
Sweating
Present
Absent
Nausea
Present
Absent
Transport facilities
Ambulance
Others
n
Median
Mean
(SEM)
p value
Corrected mean
(SEM) (hours)
p value
4
11
28
32
23
6
3.5
3
6.8
9.5
3
0.8
10 (7.4)
9 (6.3)
8.8 (1.4)
22.1 (5.3)
9.9 (4.4)
4.6 (3.9)
0.130
8 (5.4)
4.7 (2)
8.6 (1.3)
12 (1.6)
6.1 (1.5)
4.6 (3.9)
0.033
85
19
5
5.3
12.7 (2.3)
14 (5.3)
0.830
8.3 (0.9)
9 (2)
0.771
93
11
5.5
3.5
13.6 (2.3)
8 (3.9)
0.235
8.7 (0.8)
6 (2.1)
0.25
72
5.2
9.7 (1.9)
0.082
7.7 (0.9)
0.281
29
4.5
20.6 (5.7)
32
72
5.4
4.5
6.9 (1.2)
14.7 (2.9)
0.013
6.7 (1.1)
8.9 (1)
0.137
34
22
26
22
4
4.25
3.8
7.75
12.6 (4.5)
15.6 (4.9)
8.8 (2.9)
14 (4)
0.719
7.1 (1.2)
10.4 (2.1)
6.7 (1.5)
9.7 (1.5)
0.257
102
02
5.2
7
13.1 (2.2)
7 (4)
0.334
8.5 (0.8)
7 (4)
0.778
30
74
4.8
4.9
16.7 (5.3)
11.5 (2.1)
0.369
8.9 (1.6)
8 (0.9)
0.623
44
60
4
6.3
15.6 (4.3)
11.1 (1.9)
0.340
8.3 (1.3)
8.8 (1.9)
0.787
15
89
2
6.4 (3.2)
6
0.061
14.1 (2.4)
4.8 (1.9)
9 (0.9)
0.054
27
77
6.5
4.5
6.9 (1.2)
14.4 (2.8)
0.015
6.9 (1.2)
8.7 (1)
0.246
9.9 (1.8)
AMI: acute myocardial infarction
Discussion
This study describes prehospital delay times for the sample
of patients admitted to the emergency unit of our institute
for the evaluation of suspected AMI from December 2001
to June 2002. In this study population, the overall median
delay time was 5.2 hours, and door-to-drug time was 1
hour. A review of the data from studies published between
IHJ-470-03.p65
351
1969 and 1987 shows that the median prehospital delay
for patients with AMI ranged from 2.5 to 7 hours.7 These
differing delay times are likely attributable to varying
demographic and clinical characteristics of the samples
under study, definitions of symptom onset time used, and
period during which the study was conducted. In our study,
delays were not significant with respect to age and sex. In
11/19/2003, 11:25 PM
352 Malhotra et al. Prehospital Delay in Treatment of AMI
Table 2. Duration of prehospital delay and timing of
administration of thrombolytic therapy in patients with
acute myocardial infarction
Pain-to-door
time. Duration
of prehospital
delay (hours)
<1
1–1.9
2–3.9
4–5.9
6–11.9
>12
Total
n
Door-to-drug times (hours)
Median
Mean (SEM) p value*
6
16
16
10
16
2
66
0.8
0.8
0.7
1.4
1
1.5
1
1.0 (0.3)
0.1 (0.1)
1.2 (0.2)
1.4 (0.2)
1.4 (0.3)
1.5 (0.5)
1.2 (0.1)
0.627
*p value denotes the comparison of mean door-to-drug times in the various
groups of patients with different durations of prehospital delay.
contrast, earlier studies suggested that older individuals
took longer to access medical care than younger
individuals.8 This might be due to the still prevalent joint
family norms in Indian society. The median delay in patients
with a past medical history of ischemic heart disease was
not significantly different from that in patients without such
a history. Thus, the patient’s behavior was not modified by
the past experience of an acute attack. It is also interesting
to note that the majority of patients studied had no history
of angina (100 v. 4), diabetes (93 v. 11), or hypertension
(87 v. 17). It could be speculated that patients with the
above diseases were more health conscious, and took
medicines regularly. Also, prehospital delay was not
different in patients with or without the above diseases. Our
results are contradictory to those of previous studies where
patients with a history of MI and diabetes delayed longer
than those without the disease.7
Pain was the most common presenting symptom in our
study (102 v. 2). However, it was found that presenting
symptoms such as pain, dyspnea, sweating, and nausea are
not related to pain-to-door time. It has been seen that the
behavior of patients with collapse, pain or pathological
breathlessness after MI is at an instinctive level, though to
some extent, it may be culturally related.9
In contrast to previous studies, the day of the week and
time of presentation did not affect the prehospital time.
Prehospital delay was significantly higher in patients (9.9
v. 5.2 hours, p=0.002) who had visited a local practitioner
than those who came straightaway to the emergency unit
of the hospital. While the reasons for such a practice may
be speculative, we suggest that this delay in time can be
reduced if there is a 24-hour ambulance service with a
hotline and facilities for fascimile transmission of ECG. Such
IHJ-470-03.p65
352
Indian Heart J 2003; 55: 349–353
an ambulance can quickly transport patients directly to the
tertiary-care center if necessary. Secondly, general
practitioners can be formally trained to administer
streptokinase themselves, and deal with the complications
arising from streptokinase therapy.
In the present study, out of 104 patients, 66 were
thrombolyzed. Also, prehospital delay was significantly
longer in the nonthrombolysed patients (corrected mean
15 hours v. 4.6 hours). There is overwhelming evidence of
the beneficial effects provided by reperfusion strategies in
patients with AMI.10 Although various contraindications
to the administration of thrombolytic therapy presently
exist, including prolonged prehospital delay, thrombolytic
therapy is underutilized in the management of AMI.
Findings from the Worcester Heart Attack Study show that
patients who delayed for more than 6 hours were 6.5 times
less likely to receive thrombolytic agents compared to
patients who arrived within 1 hour of the onset of AMI.8
In the present study, out of 38 nonthrombolysed patients,
30 presented to the hospital after 6 hours; the remaining
either could not afford thrombolytic therapy or were
already thrombolysed. Another aspect of prehospital delay
highlighted by our study is knowledge regarding heart
attack symptoms. Patients who knew about the symptoms
of heart attack delayed less than those who were ignorant
(2.9 v. 11.9 hours). Thus, educational approaches are
essential to reduce the extent of patient delay, and to
enhance widespread use of time-dependent management
strategies in patients hospitalized with AMI.
Hospital-associated delays in administering
thrombolytic therapy: In our study, mean and median
door-to-drug times in thrombolysed patients were 1.2 (0.1)
hours and 1 (0.2–3.5) hours, respectively. However, a
previous study suggests an association of increasing delays
in thrombolytic therapy with increasing duration of prehospital delay. The National Heart Attack Alert Program
has appropriately called attention to reduction of door-todrug times. However, a few studies have examined the
relationship between the extent of prehospital and hospital
delay with thrombolytic therapy.
Limitations of the study: There are several limitations
of the present study. The effect of prehospital delay on
disease outcomes was not studied. Patients who died of AMI
outside the hospital and those with silent MI were not
studied. Appropriate caveats need to be planned for the
interpretation of study findings, since different delay
patterns may have existed in patients with poorly defined
time of onset of symptoms. The number of patients
included in the study was also small. However, our data
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Indian Heart J 2003; 55: 349–353
are representative of a typical tertiary care hospital and,
therefore, such data can be generalized to other hospitals
as well.
In conclusion, prehospital delay is the main reason for
not receiving thrombolytic therapy. The main factors
contributing to prehospital delay are: poor knowledge of
symptoms, prior treatment from local practitioners, and
unavailability of rapid transport facilities. Target
educational efforts, and provision of rapid transportation
facilities can help reduce the excessive case fatality rates
attributed to prehospital delay.
Malhotra et al. Prehospital Delay in Treatment of AMI 353
4.
5.
6.
7.
References
1. Enas EA, Garg A, Davidson MA, Nair VM, Huet BA, Yusuf S. Coronary
heart disease and its risk factors in first-generation immigrant Asian
Indians to the United States of America. Indian Heart J 1996; 48:
343–353
2. Effectiveness of intravenous thrombolytic treatment in acute
myocardial infarction. Gruppo Italiano per lo Studio della
Streptochinasi nell’ Infarto Miocardico (GISSI). Lancet 1986; 1:
397–402
3. Second International Study of Infarct Survival (ISIS-2) Steering
Committee. Intravenous streptokinase given within 0–4 hours of
IHJ-470-03.p65
353
8.
9.
10.
onset of myocardial infarction reduced mortality in ISIS-2. Lancet
1987; 1: 502–508
Goldberg RJ, McGovern PG, Guggina T, Savageau J, Rosamond WD,
Luepker RV. Prehospital delay in patients with acute coronary heart
disease: concordance between patient interviews and medical
records. Am Heart J 1998; 135: 93–99
Goff DC Jr, Feldman HA, McGovern PG, Goldberg RJ, Simons- Morton
DG, Cornell CE, et al. Prehospital delay in patients hospitalized with
heart attack symptoms in the United States: the REACT trial. Rapid
Early Action for Coronary Treatment (REACT) Study Group. Am
Heart J 1999; 138: 1046–1057
Hackett TP, Cassem NH. Factors contributing to delay in responding
to the signs and symptoms of acute myocardial infarction. Am J
Cardiol 1969; 24: 651–658
Yarzebski J, Goldberg RJ, Gore JM, Alpert JS. Temporal trends and
factors associated with extent of delay to hospital arrival in patients
with acute myocardial infarction: the Worcester Heart Attack Study.
Am Heart J 1994; 128: 255–263
Goldberg RJ, Yarzebski J, Lessard D, Gore JM. Decade-long trends and
factors associated with time to hospital presentation in patients with
acute myocardial infarction: the Worcester Heart Attack Study. Arch
Intern Med 2000; 160: 3217–3223
Rawles JM, Haites NE. Patient and general practitioner delays in acute
myocardial infarction. Br Med J 1988; 196: 882–884
Goff DC, Nichoman NZ, Ramsay DJ, et al. A population based
assessment of the use and effectiveness of thrombolytic therapy: the
Corpus Christi Heart Project. Ann Epidemiol 1995; 5: 171–178
11/19/2003, 11:25 PM
354 Roy etArticle
al. Mitral Valve Repair for Nonrheumatic Mitral Regurgitation
Original
Indian Heart J 2003; 55: 354–357
Mitral Valve Repair for Nonrheumatic
Mitral Regurgitation
Swapnadeep Roy, Shiv Kumar Choudhary, Arkalgud Sampath Kumar
Department of Cardiothoracic and Vascular Surgery, All India Institute of Medical Sciences, New Delhi
Background: We studied the results of mitral valve repair in patients with severe mitral regurgitation of
nonrheumatic etiology.
Methods and Results: Between January 1988 and April 2002, 116 patients, of which 59 were male and 57
female, with severe mitral regurgitation of nonrheumatic etiology, underwent mitral valve repair using a variety
of techniques. Their mean age was 26.4 years (range 2–67 years). The cause of mitral regurgitation was
congenital in 56 patients, myxomatous in 44, infective endocarditis in 7, and ischemic in 9. Ninety patients
were in preoperative New York Heart Association class III, and 26 in class IV. Reparative procedures included
posterior teflon felt collar annuloplasty (modified Cooley’s) in 80 patients, chordal shortening in 37, cusp excision
in 34, cleft closure in 8, chordal transfer in 6, and neochordae in 3. The early mortality was 3.4% (4 patients).
Follow-up ranged from 1 to167 months (mean 47 months), and was 95% complete. There were 2 late deaths
(1.7%). Six patients (5.2%) underwent reoperation for severe mitral regurgitation post-repair. Of the remaining
104 patients, 90 (86.5%) had no or trivial mitral regurgitation at the last follow-up. Actuarial, reoperationfree, and event-free survival at 130 months was 93%±3.6%, 89.9%±6%, and 69.7%±13.7%, respectively.
Ninety-two patients (88.5%) were in New York Heart Association class I at the last follow-up.
Conclusions: Mitral valve repair in nonrheumatic mitral regurgitation patients provides satisfactory results
with current surgical techniques, and is the preferred option in this subset of patients. (Indian Heart J 2003;
55: 354–357)
Key Words : Mitral regurgitation, Mitral valve repair, Valvular heart disease
S
urgical treatment of severe mitral regurgitation (MR)
currently involves either mitral valve (MV) repair or
replacement (mechanical prosthesis/bioprosthesis).
Although valve replacement has been the widely accepted
modality, there are numerous complications associated
with this procedure such as thrombosis, thromboembolism,
anticoagulant-related hemorrhage, and bioprosthetic
degeneration over a period of 7–15 years, necessitating a
second surgical procedure. Therefore, repair as the
preferred option, whenever possible, is gaining popularity
among cardiac surgeons.
The etiology of the MR may be rheumatic or
nonrheumatic. In the latter category, there are numerous
causes such as congenital (often associated with atrial
septal defect), myxomatous degeneration, ischemic, and
infective. While the results of repair for rheumatic valve
disease often have a late phase of deterioration due to
Correspondence: Professor A Sampath Kumar, Department of
Cardiothoracic and Vascular Surgery, Cardiothoracic Centre, AIIMS,
New Delhi 110029. e-mail: [email protected]
IHJ-507-03.p65
354
progression of the rheumatic valvulitis, the reported results
of repair in nonrheumatic cases have generally been more
satisfactory. We report our experience with repair in this
subset of patients.
Methods
From January 1988 to April 2002, 116 patients with severe
MR of nonrheumatic etiology underwent MV repair. The
age range of the patients was 2–67 years (mean age 26.4
years). Of these patients, 59 were males (50.8%), and 57
females (49.2%). The causes of nonrheumatic MR were
congenital in 56 patients (47.4%), myxomatous
degeneration with cusp prolapse in 44 (37.9%), infective
endocarditis in 7 (6%), and ischemic in 9 (7.7%). Six of the
patients had a primum ASD (partial atrioventricular septal
defect), and 46 had a secundum ASD. An isolated cleft MV
was responsible for the MR in 4 patients.1 In patients with
myxomatous degeneration, there was cusp prolapse with
chordal elongation/rupture, predominantly in the posterior
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Indian Heart J 2003; 55: 354–357
Roy et al. Mitral Valve Repair for Nonrheumatic Mitral Regurgitation 355
mitral leaflet. In the ischemic category, we included patients
with chronic ischemia only, in whom the MR was due to
papillary muscle dysfunction or chordal elongation/
rupture. Associated annular dilatation was present in all
these patients due to left ventricular dilatation. In patients
with infective endocarditis, there were primarily localized
areas of leaflet destruction, and repair was undertaken only
after an adequate course of antibiotics (at least 2 weeks).
Seventy-four patients (63.8%) were in sinus rhythm
preoperatively, and 42 in atrial fibrillation (36.2%). The
predominant presenting symptom was dyspnea on
exertion. Ninety patients were in New York Heart
Association (NYHA) class III, and 26 were in class IV.
Preoperative transthoracic echocardiography was
performed in all the patients. Cardiac catheterization and
coronary arteriography were performed in patients above
40 years of age, or if there was a suspicion of associated
aortic valve disease, or coronary artery disease. The severity
of MR was assessed by echocardiography and/or
angiography.
Surgical technique: After induction of general
anesthesia, transesophageal echocardiography (TEE) was
performed in all the patients after 1994. Intraoperatively,
the surgical approach was either a mid-sternotomy
(n=100) or a right anterolateral thoracotomy (n=16). The
latter approach was primarily used for cosmetic reasons in
young females. Before 1996, moderately hypothermic
(32 oC) cardiopulmonary bypass (CPB), and since 1996,
normothermic perfusion was used in all the patients. Coldblood cardioplegia and topical ice-slush was used for the
protection of the myocardium. Bicaval cannulation was
used in all the patients. The MV was exposed through a
standard incision in the left atrial wall behind the interatrial
groove. In patients with an ASD, the approach was through
the right atrium. After assessing the morphology, a variety
of reparative techniques were utilized, as described earlier.2–5
The adequacy of repair was confirmed by injecting saline
into the left ventricular cavity and observing the coaptation
of the leaflets. At the end of the procedure after
discontinuing CPB, TEE was performed in all the patients
treated after 1994 to confirm the adequacy of repair.
The various procedures utilized for the MV repair are as
follows: (i) posterior teflon felt collar annuloplasty (modified
Cooley’s)2 in 80 patients (68.9%); (ii) chordal shortening3
in 37 (31.9%); (iii) cusp excision (quadrangular resection
of posterior mitral leaflet) in 34 (29.3%); (iv) cleft closure
in 8 (6.9%); (v) chordal transfer in 6 (5.2%); and (vi)
neochordae in 3 (2.6%).
Associated procedures performed in these patients
IHJ-507-03.p65
355
included the following: (i) aortic valve replacement
(prosthetic) in 8 (primarily for aortic regurgitation);
(ii) aortic valvuloplasty in 15; (iii) closure of atrial septal
defect in 52; (iv) coronary artery bypass grafting in 5 (3 of
the other 4 patients with ischemic MR had prior successful
angioplasty of the diseased target vessels; the remaining
patient had scarred myocardium with no reuptake on
thallium scan).
Follow-up ranged from 1 to 168 months (mean 47
months). The follow-up was 95% complete. At each followup visit, a transthoracic echocardiogram (TTE) was
performed in all these patients to assess the status of the
MV repair, besides looking for any associated lesions.
Statistical analysis was performed using SPSS software on
a Windows operating system. Kaplan–Meier survival
estimates were derived for this group of patients.
Results
All the patients survived the operation. The mean bypass
time was 51 min (range 28–70 min), and the mean aortic
cross-clamp time was 37 min (range 21–58 min). The
mean intensive care unit stay was 2 days (range 1–6 days),
and the mean postoperative ventilation was for a period of
8 hours (range 6–72 hours). The mean postoperative stay
was 5 days (range 4–9 days).
Early mortality (30-day) was seen in 4 patients (3.4%).
In 1 patient, the cause of death was persistent low output
following the repair (preoperatively the patient was in
congestive heart failure unresponsive to medical
management). The second patient developed acute renal
failure in the immediate postoperative period and
succumbed. Two other patients died of persistent
intractable ventricular arrhythmias.
In the surviving patients, a pre-discharge TTE was
performed to evaluate the status of the MV repair. In all
the 112 patients, there was no or mild MR that correlated
well with the TEE, performed at the end of operation in the
operating room.
There were 2 late deaths (1.7%). Both patients had
developed severe left ventricular dysfunction secondary to
severe MR and succumbed before reoperation. Six patients
(5.2%) underwent reoperation for severe MR. Of these
patients, 5 had congestive heart failure, and the sixth
patient was in NYHA class III prior to reoperation. In 5 of
the 6 patients, the cause of failure of the original repair
was due to suture dehiscence of the annuloplasty, or those
used for chordal shortening. In one of them, there was
progression of the original myxomatous degeneration with
chordal rupture of originally uninvolved chordae. All the
11/19/2003, 11:26 PM
Indian Heart J 2003; 55: 354–357
356 Roy et al. Mitral Valve Repair for Nonrheumatic Mitral Regurgitation
6 patients had a prosthetic MV replacement, and survived.
Of the 104 late survivors, 92 (86.5%) are in NYHA class
I, and 12 in NYHA class II at the last follow-up. Eighty
patients (76.9%) are in sinus rhythm, while the rest are in
chronic atrial fibrillation (AF) (all of them were also in AF
preoperatively). One of the 104 late survivors (0.9%) had
a thromboembolic complication (the patient was in AF
postoperatively). There were no other complications. Of
those who were reoperated, all have improved to NYHA
class II status.
At the last follow-up, 90 of the 104 surviving patients
have no or trivial MR on echocardiography, 6 have mild
MR, and 8 have moderate-to-severe MR.
The actuarial, reoperation-free, and event-free survival
in the group of operative survivors at 130 months was
93%±3.6%, 89.9%±6%, and 69.7%±13.6%, respectively
(Kaplan–Meir estimates). Freedom from thromboembolic
events at 108 months was 98.6% (Figs 1–3).
Probability 100
at risk
111
99
103
98
86
96.8 96.8 96.8 96.8 90.5 83.7 83.7
77
74
63
52
41
19
6
Fig. 3. Probability of event-free survival in patients after mitral valve repair for
nonrheumatic mitral regurgitation (Kaplan–Meier estimates).
Discussion
Probability 100
at risk
111
100
103
99
86
99
74
99
69
99
60
97.3 95.3 92.9 92.9
52
41
17
6
Fig. 1. Probability of actuarial survival in patients of mitral valve repair for
nonrheumatic mitral regurgitation (Kaplan–Meier estimates).
Probability 100
at risk
111
99
103
99
86
97.8 97.8 97.8 97.8 95.6 95.6 89.9
76
70
64
53
42
18
4
Fig. 2. Probability of reoperation-free survival in patients after mitral valve
repair for nonrheumatic mitral regurgitation (Kaplan–Meier estimates).
IHJ-507-03.p65
356
In India, rheumatic heart disease remains the predominant
cause of MR. However, MR due to nonrheumatic causes is
not uncommon.
Repair of the MV has gradually become widely accepted,
ever since it was popularized by Carpentier.7 For nonrheumatic severe MR, repair of the MV has shown excellent
long-term durability. The Carpentier group6–8 has reported
a 15-year actuarial survival of 72.4%, with freedom from
reoperation at 15 years being 92.7%. This group
predominantly used a prosthetic ring in most of their
annuloplasty procedures. Galloway et al.9 reported on their
results with Carpentier-type MV reconstructions with an
operative mortality of 5%, and a 5-year freedom from
reoperation rate of 94.4%. Actuarial freedom from
thromboembolic complications was 93.9% at 15 years, and
96.5% were free from anticoagulant-related hemorrhage.
Similar results have been reported by other groups also.
Overall, the results are better than those reported with
prosthetic MV replacement.10
Our results compare favorably with other reports in the
literature. Our 10-year survival of about 93% with a
reoperation-free rate of 89% is comparable to most reported
series. Functional rehabilitation and the absence of
medication are marked advantages. Preservation of left
ventricular function is another advantage.
Conclusion: Repair of the MV rather than its replacement
should be the procedure of choice in patients with nonrheumatic MR.
11/19/2003, 11:26 PM
Indian Heart J 2003; 55: 354–357
Roy et al. Mitral Valve Repair for Nonrheumatic Mitral Regurgitation 357
Acknowledgments
The authors acknowledge the help provided by the residents
of the department for the excellent record-keeping that
greatly facilitated the analysis of results. We would also like
to thank Mr Rajbir of the Department of Biostatistics, for
the statistical analysis.
References
1. Mohanty SR, Choudhary SK, Ramamurthy S, Kumar AS. Isolated
congenital anterior mitral leaflet cleft: a rare cause of mitral
insufficiency. J Heart Valve Dis 1999; 8: 67–70
2. Kumar AS, Kumar RV, Shrivastava S, Venugopal P, Sood AK, Gopinath
N. Mitral valve reconstruction. Early results of a modified Cooley
technique. Tex Heart Inst J 1992; 19: 107–111
3. Kumar AS, Bhan A, Kumar RV, Shrivastava S, Sood AK, Gopinath N.
Cusp-level chordal shortening for rheumatic mitral regurgitation.
Early results. Tex Heart Inst J 1992; 19: 47–50
IHJ-507-03.p65
357
4. Kumar AS, Rao PN. Restoration of pliability to the mitral leaflets
during reconstruction. J Heart Valve Dis 1995; 4: 251–253
5. Choudhary SK, Talwar S, Dubey B, Chopra A, Saxena A, Kumar AS.
Mitral valve repair in a predominantly rheumatic population. Longterm results. Tex Heart Inst J 2001; 28: 8–15
6. Deloche A, Jebara AV, Relland JY, Chauvaud S, Fabiani JN, Perier P,
et al. Valve repair with Carpentier techniques. The second decade. J
Thorac Cardiovasc Surg 1990; 99: 990–1001
7. Carpentier A. Cardiac valve surgery—the “French correction”. J
Thorac Cardiovasc Surg 1983; 86: 323–337
8. Carpentier A, Chauvaud S, Fabiani JN, Deloche A, Relland J, Lessana
A, et al. Reconstructive surgery of mitral valve incompetence: tenyear appraisal. J Thorac Cardiovasc Surg 1980; 79: 338–348
9. Galloway AC, Colvin SB, Baumann FG, Grossi EA, Ribakove GH,
Harty S, et al. A comparison of mitral valve reconstruction with
mitral valve replacement: intermediate-term results. Ann Thorac Surg
1989; 47: 655–662
10. Sand ME, Naftel DC, Blackstone EH, Kirklin JW, Karp RB. A
comparison of repair and replacement for mitral valve incompetence.
J Thorac Cardiovasc Surg 1987; 94: 208–219
11/19/2003, 11:26 PM
358 Srimannarayana
Original
Article et al.
Indian Heart J 2003; 55: 358–361
Left Atrial Thrombus in Mitral Stenosis
Prevalence of Left Atrial Thrombus in Rheumatic Mitral
Stenosis With Atrial Fibrillation and its Response to
Anticoagulation: A Transesophageal
Echocardiographic Study
J Srimannarayana, RS Varma, S Satheesh, R Anilkumar, J Balachander
Department of Cardiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry
Background: The frequency of occurrence of left atrial thrombi, and the effect of anticoagulation in patients
with rheumatic mitral stenosis and atrial fibrillation is not well established. This study was conducted to evaluate
the occurrence of left atrial body and left atrial appendage clots in patients with rheumatic mitral stenosis and
atrial fibrillation, and to document the effect of long-term anticoagulation on clot dissolution.
Methods and Results: Consecutive patients with severe rheumatic mitral stenosis and atrial fibrillation were
assessed by transesophageal echocardiography. Those with left atrial body or left atrial appendage clots were
anticoagulated with oral nicoumalone. Transesophageal echocardiography was then repeated in patients on
anticoagulation who were on regular follow-up, and in whom percutaneous transvenous mitral commissurotomy
could be considered. Of the 490 patients studied, 163 had left atrial body or left atrial appendage clots. A repeat
transesophageal echocardiographic examination was done in 50 patients who had optimal anticoagulation for
a period of 6 months. Only 2 of the 17 patients who had left atrial body clots had successful clot dissolution after
long-term anticoagulation, while the left atrial appendage clots disappeared in 31 of 33 patients (p<0.001).
Conclusions: Left atrial clots are present in a third of patients with severe rheumatic mitral stenosis and atrial
fibrillation. Isolated left atrial appendage clots in patients with rheumatic mitral stenosis and atrial fibrillation
can disappear with long-term anticoagulation, while thrombi that extend into the left atrial body may persist
despite optimal anticoagulation. (Indian Heart J 2003; 55: 358–361)
Key Words: Rheumatic mitral stenosis, Left atrial thrombi, Echocardiography
R
heumatic mitral stenosis with atrial fibrillation (AF) is
a common clinical problem in India. It is associated
with a very high risk of embolic cerebrovascular accidents,
which is reported to be as much as seventeen times greater
than in unaffected controls.1
Transesophageal echocardiography (TEE) is well
established as the gold standard for detecting thrombi in
the left atrium (LA) and the LA appendage. The sensitivity
and specificity of TEE are reported to be 100% and 99%,
respectively.2 The semi-invasive nature and safety of the test
make it ideal for serial follow-up of thrombi in the LA body
and appendage. Though it is known that thrombi are
common in patients with mitral stenosis and AF, only small
studies have documented the exact frequency of occurrence
Correspondence: Professor R Anilkumar, Department of Cardiology,
JIPMER, Pondicherry 605006. e-mail: [email protected]
IHJ-527-03.p65
358
of these thrombi, and their fate on optimal oral
anticoagulation.
The objectives of this study were to document the
frequency of occurrence of LA body and appendage clots
in patients with severe mitral stenosis and AF, and to study
the effect of oral anticoagulation on clot dissolution.
Methods
Consecutive patients with severe mitral stenosis and AF,
who were being evaluated for percutaneous transvenous
mitral commissurotomy (PTMC), underwent TEE
evaluation. Patients were excluded from the study if there
was considerable mitral regurgitation or aortic valve disease.
A total of 490 patients (343 females [70%], and 147 males
[30%]) were included in the study. The mean age of these
patients was 27.4±8.41 years (range 21–65 years).
11/19/2003, 11:26 PM
Indian Heart J 2003; 55: 358–361
Srimannarayana et al. Left Atrial Thrombus in Mitral Stenosis 359
An ACUSON 128-XP echocardiographic system
equipped with omniplane and biplane transesophageal
probes was used for this study. TEE was performed according
to the standard procedure after obtaining informed consent.
All the patients were put on oral anticoagulation with
nicoumalone. The international normalized ratio (INR) was
maintained between 2.5 and 3.5. Repeat TEE was
performed after 6 months in patients (i) with LA body or
LA appendage clots; (ii) on regular anticoagulation, and
follow-up with INR; and (iii) with valve morphology
suitable for PTMC.
Patients who were very sick (in NYHA class IV), and
those whose valve morphology precluded PTMC were
immediately referred for appropriate surgery.
Of the patients undergoing repeat TEE, patients with an
isolated LA appendage clot (group A) were compared with
patients in whom the thrombus extended into the LA body
or who had isolated LA body clots (group B). The group
with successful clot dissolution, and the group with
persistence of the thrombus were also compared.
Continuous variables were expressed as mean values
with standard deviation, while proportions were presented
as numbers and percentages of the total. The significance
of differences between means was tested by the Student’s
t test, while that between proportions was tested with the
Chi-square test. A p value <0.05 was considered significant.
Results
Incidence and location of thrombi: Of the 490 patients
who underwent TEE, LA clots were present in 163 (33.2%).
Isolated LA appendage clots were found in 88 patients
(18%). Isolated LA body clots or LA appendage clots
extending into the LA body were found in 75 patients
(15.3%). LA spontaneous echocardiographic contrast
(LASEC) was present in 365 patients (74.5%). None of the
patients had right atrial thrombi.
Resolution of thrombi: TEE was repeated after 6 months
of optimal oral anticoagulation in 50 out of 163 patients.
These patients had maintained their INR in the range of
2.5–3.5, and were on regular follow-up. Nearly half the
patients (48%) were above the age of 35 years (range 21–
55 years). None of these patients had any other risk factors,
such as diabetes mellitus, hypertension or smoking. A
comparison of the baseline characteristics, echocardiographic parameters, and mean INR between the group of
patients with isolated LA appendage clots (n=33) and the
group with clots extending to the LA body (n=17) is given
in Table 1. There were no statistically significant differences
among these parameters between the two groups.
IHJ-527-03.p65
359
Table 1. Comparison of patients who underwent repeat
TEE with isolated LA appendage clot versus those with
clots extending to the LA cavity
Characteristic
Group A
(n=33)
Group B
(n=17)
p value
Mean age (years)
Males
Females
Mean MVO (cm2)
Mean MPG (mmHg)
Mean LA size (AP diameter, cm)
Mitral regurgitation (grade 1/4)
Mean INR
33.91±7.82
10 (30.3%)
23 (69.7%)
0.9±0.15
20.15±4.7
3.73±0.6
7 (21.2%)
2.87±0.3
33.8±9.01
9 (52.9%)
8 (47.1%)
0.96±0.14
22.06±4.51
3.71±0.5
4 (23.5%)
2.89±0.23
ns
ns
ns
ns
ns
ns
ns
Group A: patients with isolated LA appendage clot; Group B: patients with clots
extending to the body of the LA or isolated LA body clots; MVO: mitral valve orifice;
MPG: mean pressure gradient; AP: anteroposterior; INR: international normalized
ratio; ns: not significant; LA: left atrial; TEE: transesophageal echocardiography
No clots were detected on repeat TEE in 31 out of 33
patients (93.9%) with isolated LA appendage clots (Figs 1
and 2). These 31 patients underwent PTMC successfully.
Only 2 out of 17 patients (11.8%) with a previous LA body
clot had no detectable clots. Patients with persistent LA clots
were referred for an open mitral valvotomy and
thrombectomy. A comparison between those in whom the
clot disappeared, and those in whom the clot persisted
revealed that the location of the LA clot (isolated LA
appendage v. LA body) alone was a significant predictor of
thrombus dissolution. There were no statistically significant
differences in other parameters, such as valve orifice, LA
size, mitral regurgitation, age, gender, and INR values
between these groups.
Fig. 1. Isolated left atrial appendage clot before anticoagulation.
Discussion
Conventional transthoracic echocardiography (TTE) has a
poor yield in the detection of LA appendage thrombi.3 The
posterior location of the LA in the chest as well as the poor
11/19/2003, 11:26 PM
360 Srimannarayana et al. Left Atrial Thrombus in Mitral Stenosis
Fig. 2. The same patient as in Fig. 1, showing no left atrial appendage
thrombus after anticoagulation for 6 months.
visualization of the LA appendage contribute to the lack of
accuracy of TTE. On the other hand, TEE is an excellent
method for detecting atrial thrombi, especially those located
in the LA appendage.
There are few reports on the prevalence of LA body and
LA appendage clots in patients with severe mitral stenosis
and AF. In a small group of 50 patients with mitral stenosis
and AF, Hwang et al.4 observed an LA thrombus in 28
patients (56%) by TEE. In another small study of 22 patients
with mitral stenosis and AF, Karatasakis et al.5 observed
an LA thrombus in 12 patients (54%). In our study of 490
patients, the prevalence was 33.5%. Considering the size
of the study group, this can be considered a representative
figure for the prevalence of LA thrombi in patients with
severe mitral stenosis and AF. Thus, it can be stated that 1
out of every 3 patients with severe mitral stenosis and AF
will have an LA thrombus.
Anticoagulation is conventionally used to reduce the risk
of the thromboembolic events associated with AF. Oral
anticoagulants act by inhibiting the synthesis of vitamin
K-dependent coagulation factors. This prevents new
thrombus formation, and promotes adherence and
organization of old thrombi to the surrounding
endocardium.6–8 However, recent studies have supported
an alternative hypothesis of benefit that includes not only
the prevention of new thrombus formation but also the
resolution of existing thrombi.9
In situations in which a thrombus is already present,
anticoagulation prevents further thrombus extension,
thereby facilitating the action of endogenous fibrinolysis.
A study conducted by Kandpal et al.10 showed that 41.7%
of isolated LA appendage clots resolved in contrast to 12.5%
of LA body clots in patients with mitral stenosis after 6
months of oral anticoagulation. Resolution of atrial
IHJ-527-03.p65
360
Indian Heart J 2003; 55: 358–361
thrombi after oral anticoagulation in patients with
nonvalvar AF has also been examined in several studies.11,12
In the present study, it was seen that thrombi in the LA
appendage disappeared on anticoagulation, whereas
thrombi in the LA body did not. Success in resolving LA
appendage thrombi vis-à-vis LA body thrombi is crucial,
given that most clinically encountered thrombi are located
in the LA appendage. This difference is possibly explained
by the fact that patients with an LA body clot have a higher
clot burden, which does not permit dissolution with
endogenous fibrinolysis despite optimal anticoagulation. It
is probable that clots localized to the LA appendage, with a
much smaller clot burden, are dissolved by endogenous
fibrinolysis, while effective oral anticoagulation prevents
fresh thrombus formation.
A study conducted by Murillo et al.13 showed that PTMC
can be performed in patients with an LA appendage clot
with TEE guidance and fluoroscopic control. However, this
can be fraught with the risk of embolism. Hence, the
interventional cardiologist will always prefer the LA and
LA appendage to be free of clots before embarking on
balloon mitral valvotomy. Based on our study, it is possible
to evolve a strategy of treatment in patients with severe
mitral stenosis, AF, and LA thrombus. Patients with an LA
thrombus extending well into the LA body can be directly
referred for surgery, since they are unlikely candidates for
closed procedures. However, patients with isolated LA
appendage clot and mitral stenosis can afford to be on
anticoagulation for a period of 6 months, and then undergo
a repeat TEE, especially if they can be stabilized to NYHA
class II or less. If the clot resolves, as in a good percentage
of our subjects, these patients can undergo PTMC.
Some limitations of our study have to be emphasized. A
repeat TEE was done in only about one-third of the patients
with LA clots. The rest of the patients did not undergo a
repeat TEE as part of the study because of one or more of
the following reasons: valve morphology precluded PTMC,
NYHA class III or class IV patients who were judged to need
early surgical treatment, suboptimal anticoagulation, and
irregular follow-up. Thus, the results of the study should
be interpreted with some caution, and a further, large-scale
study may be necessary to confirm the findings of our study.
The effect of anticoagulation on LASEC was not studied
since the mere presence of LASEC was not considered to be
a contraindication for PTMC. Also, it was not practically
possible to determine the duration of AF in these patients,
and correlate it with clot prevalence and resolution.
Conclusions: One-third of patients with severe mitral
stenosis and AF have LA body or LA appendage clots.
Isolated LA appendage clots in patients with rheumatic
11/19/2003, 11:26 PM
Indian Heart J 2003; 55: 358–361
Srimannarayana et al. Left Atrial Thrombus in Mitral Stenosis 361
mitral stenosis and AF can disappear with long-term
anticoagulation. Such patients may become favorable
candidates for PTMC. Clot dissolution with oral
anticoagulation is unlikely in those with an LA body clot.
These patients can be referred early for open mitral
valvotomy and thrombectomy.
8.
References
9.
1. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic
features of chronic atrial fibrillation: the Framingham study. N Engl
J Med 1982; 306: 1018–1022
2. Manning WJ, Weintraub RM, Waksmonski CA, Haering JM, Rooney
PS, Maslow AD, et al. Accuracy of transesophageal echocardiography for identifying left atrial thrombi. Ann Intern Med 1995;
123: 817–822
3. Aschenberg W, Schluter M, Kremer P, Schroder E, Siglow V, Bleifeld
W. Transesophageal two-dimensional echocardiography for the
detection of left atrial appendage thrombus. J Am Coll Cardiol 1986;
7: 163–166
4. Hwang JJ, Chen JJ, Lin SC, Tseng YZ, Kuan P, Lien WP, et al. Diagnostic
accuracy of transesophageal echocardiography for detecting left
atrial thrombi in patients with rheumatic heart disease having
undergone mitral valve operations. Am J Cardiol 1993; 72: 677–681
5. Karatasakis GT, Gotsis AC, Cokkinos DV. Influence of mitral
regurgitation on left atrial thrombus and spontaneous
IHJ-527-03.p65
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6.
7.
10.
11.
12.
13.
echocardiographic contrast in patients with rheumatic mitral valve
disease. Am J Cardiol 1995; 76: 279–281
Goldman M. The management of chronic atrial fibrillation. Prog
Cardiovasc Dis 1960; 2: 465–479
Mancini GB, Goldberg AL. Cardioversion of atrial fibrillation:
consideration of embolization, anticoagulation, prophylactic
pacemaker, and long-term success. Am Heart J 1982; 104: 617–621
Tsai LM, Hung JS, Chen JH, Lin LJ, Fu M. Resolution of left atrial
appendage thrombus in mitral stenosis after warfarin therapy. Am
Heart J 1991; 121: 1232–1234
Collins LJ, Silverman DI, Douglas PS, Manning WJ. Cardioversion of
nonrheumatic atrial fibrillation. Reduced thromboembolic
complications with 4 weeks of precardioversion anticoagulation are
related to atrial thrombus resolution. Circulation 1995; 92: 160–163
Kandpal B, Garg N, Anand KV, Kapoor A, Sinha N. Role of oral
anticoagulation and inoue balloon mitral valvulotomy in presence
of left atrial thrombus: a prospective serial transesophgeal
echocardiographic study. J Heart Valve Dis 2002; 11: 594–600
Corrado G, Tadeo G, Beretta S, Tagliagambe LM, Manzillo GF, Spata
M, et al. Atrial thrombi resolution after prolonged anticoagulation
in patients with atrial fibrillation. Chest 1999; 115: 140–143
Jaber WA, Prior DL, Thamilarasan M, Grimm RA, Thomas JD, Klein
AL, et al. Efficacy of anticoagulation in resolving left atrial and left
atrial appendage thrombi: a transesophgeal echocardiographic study.
Am Heart J 2000; 140: 150–156
Murillo H, Ayala F, Lepe L, Madrid R, Solorio S, Lara A, et al.
[Percutaneous mitral commissurotomy in patients with mitral valve
stenosis and thrombosis of the left atrium.] Arch Inst Cardiol Mex
1999; 69: 134–138
11/19/2003, 11:26 PM
362 Mishra
et al. Percutaneous Balloon Angioplasty of
Original
Article
Membranous Obstruction
Indian Heart J 2003; 55: 362–364
Percutaneous Balloon Angioplasty of Membranous
Obstruction of the Inferior Vena Cava
TK Mishra, SN Routray, M Behera, UK Patnaik, C Satapathy
Department of Cardiology, SCB Medical College, Cuttack, Orissa
Background: Membranous obstruction of the inferior vena cava is common in African and Asian countries.
Methods and Results: Between January 1999 and January 2002, 19 patients were prospectively studied. The
mean age of the patients was 38±6.9 years. All of them had swelling of the abdomen and ankle edema. Five
patients (26.3%) had jaundice, 9 (47.3%) had hepatomegaly, and 5 (26.3%) splenomegaly. Ultrasonography
could detect the site of obstruction in 18 patients (94.7%). Vena cavography demonstrated obstruction of the
inferior vena cava at the level of the diaphragm, with 2 patients (10.5%) having additional intrahepatic
obstruction. The mean pressure gradient was 22±3.5 mmHg. Seventeen patients underwent balloon angioplasty
using a Joseph balloon. The procedure was successful in 15 patients (88.2%). The post-angioplasty mean pressure
gradient was 5±1.4 mmHg. On follow-up, 3 patients (20%) developed features of restenosis; out of them, 2
underwent successful redilatation.
Conclusions: Balloon angioplasty of membranous obstruction of the inferior vena cava is feasible with a high
success rate, without any rupture of the inferior vena cava. (Indian Heart J 2003; 55: 362–364)
Key Words: Inferior vena cava obstruction, Balloon angioplasty, Percutaneous intervention
M
embranous obstruction of the inferior vena cava
(MOVC) is relatively common in Asia and Africa.1
Many cases have been reported from India.2 MOVC is one
of the important causes of Budd–Chiari syndrome.
Intervention is often necessary, as medical treatment is
ineffective. The disease should be managed early, because
long-standing MOVC can result in hepatocellular
carcinoma.1 Till the introduction of balloon dilatation for
treating MOVC cases, surgery was the only option available.
Here, we report our experience with balloon angioplasty
for managing these cases.
Methods
Between January 1999 and January 2002, 19 patients who
were clinically diagnosed to have inferior vena cava (IVC)
obstruction were taken up for the study. The disease was
suspected when the patients presented with ankle edema,
ascites, and prominent veins over the abdomen and back,
with the direction of blood flow from below upwards. After
taking a careful history, detailed physical examination was
Correspondence: Dr SN Routray, Department of Cardiology, Qr. No. 3R-8,
Near Cancer Wing, SCB Medical College, Cuttack 753007.
e-mail: [email protected]
IHJ-413-03.p65
362
carried out in all the patients. Hematological tests,
coagulation profile, liver function tests, and abdominal
ultrasound with Doppler study of the IVC was undertaken.
After clinical diagnosis, the patients were taken up for
inferior vena cavography, and subsequent angioplasty.
Catheterization and angiography of the IVC was done
through the femoral vein with a pigtail catheter.
Simultaneous right atrial catheterization was done through
the antecubital vein for simultaneous measurement of the
pressure gradient between the IVC and right atrium (RA).
If the vena cavography demonstrated a complete
obstruction, the IVC was first punctured by the stiff end of
a guidewire inserted through a multipurpose catheter.
Predilatation of the lesion was initially done with a
peripheral angioplasty balloon (3×20 mm) if the Joseph
balloon could not be negotiated across the site of the lesion.
Angioplasty was attempted with the Joseph balloon, which
is commonly used for balloon mitral valvotomy. The size of
the balloon used varied from 22 to 24 mm, depending upon
the size of the IVC. After the balloon was placed across the
lesion, it was inflated and deflated 2–3 times. Repeat
venography was done to show blood flow towards the RA.
The success of the procedure was confirmed by
demonstrating reduction or disappearance of the gradient
between the IVC and RA.
11/19/2003, 11:24 PM
Indian Heart J 2003; 55: 362–364
Mishra et al. Percutaneous Balloon Angioplasty of Membranous Obstruction 363
Results
Nineteen patients were initially diagnosed to have MOVC.
The mean age at presentation was 38±6.9 years. The mean
duration of illness was 3.5±0.6 years. The male:female
ratio was 16:3. The chief complaints were pain in the
abdomen in 15 patients (79%), and anorexia in 18 (94.7%).
All the patients complained of swelling of the abdomen and
ankle edema: 5 (26.3%) had jaundice. In all the patients,
the veins of the anterior abdominal wall and back were
prominent, with the direction of blood flow from below
upwards. Nine patients (47.3%) had hepatomegaly, and 5
(26.3%) splenomegaly.
The mean hemoglobin concentration was 8±1.3 g/dl.
The TLC and platelet count were normal. One patient had
a prolonged prothrombin time. Abnormal liver function,
as assessed by serum albumin and alanine transferase, was
present in 5 patients (26.3%).
Ultrasonography and Doppler study of the IVC
demonstrated the site of obstruction in 18 patients (94.7%).
Before the ultrasound examination, 5 patients (26.3%)
were diagnosed to have cirrhosis of the liver. Inferior vena
cavography demonstrated the site of obstruction of the IVC
at the level of the diaphragm in all the patients. Two patients
(10.5%) had an additional obstruction in the hepatic vein;
they were referred for surgical intervention. Of the
remaining 17 patients selected for angioplasty, 13 (76.4%)
had complete obstruction, and 4 (23.6%) had partial
obstruction, with a meatus <3 mm. The mean pressure
gradient between the IVC and RA was 22±3.5 mmHg.
Fifteen patients (88.2%) underwent successful balloon
dilatation without any rupture of the IVC. The procedure
was abandoned in 2 patients (11.8%), because of inability
to cross the lesion. The post-procedure mean gradient in
successful cases was 5±1.4 mmHg.
All the 15 patients who underwent successful dilatation
were followed up for a mean period of 8 months (range 3–
24 months). Three patients (20%) developed recurrence
of symptoms such as ascites. Two of them underwent
successful redilatation following the demonstration of
restenosis in the cavogram. One patient refused a repeat
procedure.
Discussion
Chronic Budd–Chiari syndrome can be due to multiple
causes. The impediment to blood flow can occur anywhere
from the RA to the small radicles of the hepatic vein. MOVC
accounts for 40% cases of Budd–Chiari syndrome in
Africa. 3 It is still not known whether the obstructing
membrane is congenital or acquired. Yamamoto et al.4 have
IHJ-413-03.p65
363
classified MOVC into 3 groups. In group A, there was
incomplete obstruction of the IVC, in group B the
obstructing membrane was complete and thin; in group C
the membrane was complete and thick. Of the 17 patients
who were taken up for angioplasty in our series, the
membrane was complete in 13 (76.4%).
The mean age at presentation in our patients was
38±6.9 years. The majority of MOVC patients were also
between 30–40 years of age in the series reported from
South Africa by Simson.1 In our series, jaundice was evident
in 5 cases (26.3%). It was present in 5.8% of patients in
the series reported by Kohli et al.5 The high incidence of
jaundice in our cases was probably due to late presentation
of the patients. Ultrasound examination revealed the site
of obstruction in 94.7% of our patients. Kohli et al.5 could
identify obstruction of the IVC by plain ultrasonography in
91% of cases.
In our series, 2 patients (10.5%) had additional
obstruction of the hepatic vein. Combined obstruction has
been reported in 7 out of 75 cases studied by Kohli et al.5
Medical treatment is ineffective.6 Previously, surgical
options included membranotomy, done by a finger7 or metal
bougie, 8 or cavoatrial shunts done to bypass the
obstruction.
Angioplasty has become the treatment of choice for
MOVC. Successful dilatation has been reported in 93.3%–
100% of cases from India.5,9 In our series, procedural
success was 88.2%. In all our successful cases, the site of
complete obstruction could be punctured by the stiff end
of the guidewire. The obstruction can also be pierced by
Brockenbrough’s septal puncture needle, which was used
by Kar et al.9 and Patel et al.10 with excellent results.
In earlier studies, either a pulmonary balloon 8 or Inoue
balloon11,12 has been used to dilate an obstruction of the
IVC. We attempted dilatation using a Joseph balloon with
gratifying results. It is safe with a high success rate. The
balloon could be reused several times, which is important,
as the majority of our patients are poor.
Restenosis was detected in 20% of our patients during
follow-up. 14.3% of cases developed restenosis in the series
by Kohli et al.5 Tyagi et al.,13 however, reported a very high
incidence (36.4%) of restenosis.
Conclusions: Membranous obstruction of the IVC can give
rise to substantial morbidity because of massive ascites and
ankle edema. A high index of suspicion is necessary, as the
disease is often confused with cirrhosis of the liver.
Ultrasonography with Doppler study of the IVC can be
diagnostic, though vena cavography is required for
confirmation. In the majority of patients, obstruction can
be successfully tackled by balloon angioplasty without
11/19/2003, 11:24 PM
364 Mishra et al. Percutaneous Balloon Angioplasty of Membranous Obstruction
fear of rupture of the IVC. Long-term follow-up of postangioplasty patients is necessary to further validate the
success of the procedure.
References
1. Simson IW. Membranous obstruction of the inferior vena cava and
hepatocellular carcinoma in South Africa. Gastroenterology 1982;
82: 171–178
2. Victor S, Jayanthi V, Kandaswamy I, Ratnasabapathy A,
Madanagopalan N. Retrohepatic cavoatrial bypass for coarctation
of inferior vena cava with a polytetrafluoroethylene graft. J Thorac
Cardiovasc Surg 1986; 91: 99–105
3. Schafer OF, Sorrell MF. Vascular diseases of liver. In: Sleisenger and
Fordtran’s gastrointestinal and liver diseases. 6th ed. 1998. p. 1189
4. Yamamoto S, Yokoyama Y, Takeshige K, Iwatsuki S. Budd–Chiari
syndrome with obstruction of the inferior vena cava. Gastroenterology
1968; 54: 1070–1084
5. Kohli V, Pande GK, Dev V, Reddy KS, Kaul U, Nundy S. Management
of hepatic venous outflow obstruction. Lancet 1993; 342: 718–722
6. Ahn SS, Yellin A, Sheng FC, Colonna JO, Goldstein LI, Busuttil RW.
Selective surgical therapy of Budd–Chiari syndrome provides
superior survivor rates than conservative medical management.
J Vasc Surg 1987; 5: 28–37
IHJ-413-03.p65
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Indian Heart J 2003; 55: 362–364
7. Hirooka M, Kimura C. Membranous obstruction of the hepatic
portion of the inferior vena cava. Surgical correction and etiological
study. Arch Surg 1970; 100: 656–663
8. Rogers MA, Chesler E, Ou Plesis L, Jeffe N, Jouvert E. Membranous
obstruction of the hepatic segment of inferior vena cava. Br J Surg
1967; 54: 221–225
9. Kar AK, Mandal M. Percutaneous balloon angioplasty of inferior
vena cava stenosis. Cardiology Today 1999; 5: 221–228
10. Patel T, Shah S, Sanghvi K, Fonseca K. Successful stenting of a
complex inferior vena cava stenosis using a modified sharp
recanulization technique. Catheter Cardiovasc Interv 2001; 52:
492–495
11. Bahl VK, Bhargava B, Chandra S. Percutaneous balloon dilatation
of IVC obstruction using Inoue Catheter. Indian Heart J 1997; 49:
427–428
12. Yang XL, Cheng TO, Chen CR. Successful treatment by percutaneous
balloon angioplasty of Budd–Chiari syndrome caused by
membranous obstruction of inferior vena cava: 8-year follow-up
study. J Am Coll Cardiol 1996; 28: 1720–1724
13. Tyagi S, Jain BL, Kumar N, Lahoti D, Arora R. Balloon dilatation of
inferior vena cava stenosis in Budd–Chiari syndrome. J Assoc
Physicians India 1996; 44: 378–380
11/19/2003, 11:24 PM
Indian Heart J 2003; 55: 365–367
Goel et al. Thrombin Injection for Femoral Artery Pseudoaneurysm
365
Brief Report
Sonographically Guided Thrombin Injection for the
Treatment of Femoral Artery Pseudoaneurysm
Pravin K Goel, Nitin Modi, Sanjay Saran Baijal, Manoj Kathuria, Surendra K Agrawal
Departments of Cardiology, Radiology, and Cardiovascular and Thoracic Surgery,
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow
The formation of pseudoaneurysm in the femoral artery after cardiac catheterization is a well-recognized
complication occurring in 1%–4% of cases. It is traditionally managed surgically and has a high morbidity.
Prolonged ultrasound-guided compression of the neck of the pseudoaneurysm, and ultrasound-guided injection
of thrombin into the aneurysm are newer modalities of treatment especially for small aneurysms. We describe
the case of a giant pseudoaneurysm of the right femoral artery, post-arteriography, which was successfully
managed with ultrasonographically guided percutaneous thrombin injection. (Indian Heart J 2003; 55:
365–367)
Key Words: Pseudoaneurysm, Femoral artery, Thrombin
F
emoral artery pseudoaneurysm is an uncommon but
well-recognized complication after percutaneous
arterial catheterization. The incidence of pseudoaneurysm
formation is reported to be up to 1% after diagnostic studies,
and 3.2% after interventional procedures.1,2 Traditionally,
these pseudoaneurysms require reparative surgery. In
1986, Cope et al. described the technique of percutaneous
thrombin injection for small pseudoaneurysm in the iliac,
femoral, and popliteal arteries.3 There is, however, limited
experience with this technique on large aneurysms. We
describe a case of a large pseudoaneurysm successfully
managed with percutaneous intra-aneurysmal injection of
bovine thrombin.
Case Report
A 66-year-old hypertensive, nondiabetic, nonsmoker male
underwent diagnostic cardiac catheterization through the
right femoral artery using 6 F arterial sheath. Five thousand
units of heparin was given during the procedure, and post
procedure, the right lower limb was immobilized for 6
hours. After 6 hours, the patient was allowed to carry out
his routine activities and was to be discharged the following
day. However, about 18 hours post procedure, the patient
complained of severe pain in the right groin with obvious
swelling of the thigh. There was no external bleeding from
the puncture site. Doppler study of the femoral artery
Correspondence: Dr PK Goel, Department of Cardiology, SGPGIMS, Rae
Bareli Road, Lucknow 226014. e-mail: [email protected]
IHJ-486-03.p65
365
showed a large pseudoaneurysm (10×4×4 cm) with a
narrow neck of 0.5 cm. The aneurysm was largely located
anterior to the femoral artery all along its length, for up to
about 10 cm below the puncture site. Ultrasound-guided
compression of the neck was tried but was not successful.
Considering the large size of the aneurysm,
ultrasonographically guided thrombin injection into the
pseudoaneurysm was planned.
Technique: After taking informed consent, a complete
Doppler assessment of the aneurysm and the patency of
distal run-off was obtained. The right groin was prepared,
draped and an echo-probe placed directly over the
pseudoaneurysm. The flow into the aneurysm was assessed
by both the color and angio modes on the HP Sonos 5500
machine. Obliteration of flow into the aneurysm was
confirmed by compression of the neck of the
pseudoaneurysm with the color mode on. Under local
anesthesia, a 22-gauge spinal needle was then passed
percutaneously directly into the pseudoaneurysm cavity
under ultrasonographic guidance. The tip of the needle was
positioned within the center of the cavity, to keep it away
from the neck. A small 2 ml syringe containing bovine
thrombin (Parke Davis) 1000 U/ml concentration was
attached to the needle and 1 ml injected into the cavity with
continuing compression of the neck. The echogenicity
within the aneurysm was seen to increase immediately, but
on color Doppler study repeated after 3–4 min, some flow
into the cavity was still seen. Thrombin injection was
repeated using the same technique and, this time, dense
11/19/2003, 11:25 PM
Indian Heart J 2003; 55: 365–367
366 Goel et al. Thrombin Injection for Femoral Artery Pseudoaneurysm
a
b
c
d
e
f
Figs. 1–6. Ultrasonographic pictures in angio mode demonstrating thrombin
injection into the femoral artery pseudoaneurysm and thrombus formation. (a)
Origin of the pseudoaneurysm from the femoral artery with a narrow neck seen
in the angio mode. (b) Giant pseudoaneurysm and blood flow into the aneurysm
seen in the angio mode, (c) Injection needle positioned into the aneurysm while
maintaining compression on the neck of pseudoaneurysm. (d) Thrombin being
injected into the aneurysm while continuing pressure on the aneurysmal neck.
The injection stream is highlighted in the angio mode with no other flow into
aneurysm during the injection. (e) Formation of post-injection thrombus, i.e.
density of aneurysm changed within 3 min. (f) Compression released and still no
flow occurring into the aneurysm with the pseudoaneurysm neck seen as a stump.
echogenicity developed within seconds. Repeat study after
3–4 min showed no flow into the cavity, without any
arterial compression. Good distal run-off on color Doppler
was confirmed before the end of the procedure. As a
precautionary measure the patient was kept on bed rest
with the right lower limb immobilized for another 6 hours
to ensure clotting of any small nonthrombosed lobulation
that might have been left. Repeat Doppler study done after
24 and 48 hours showed total thrombosis within the
pseudoaneurysm cavity, which by then had also regressed
in size, and there was no flow into the aneurysm cavity.
Discussion
With the increasing number of cardiac catheterization
procedures being performed, the total number of
cases with complications are bound to increase.
Pseudoaneurysm formation of the the femoral artery
IHJ-486-03.p65
366
occurs in 1%–3% of cases following percutaneous arterial
catheterization.1,2 The treatment options are surgical repair,
covered stents, coil embolization or, ultrasound-guided
compression and direct percutaneous thrombin injection.
Operative repair is usually associated with high morbidity
secondary to delayed ambulation and/or wound infection.
Fellmeth 4 in 1991 described ultrasound-guided
compression repair. With this treatment, flow into the
pseudoaneurysm is halted by applying pressure with the
ultrasound probe to the neck of the pseudoaneurysm and
maintaining such pressure until spontaneous thrombosis
of the aneurysm cavity occurs. This procedure, however, is
often very painful, and has an overall success rate as low as
45% to up to 100%, but a recurrence rate of up to 30%.5–7
The technique of ‘clotting aneurysm’ by direct injection
of diluted thrombin was first described in 1986 by Cope et
al.3 For the next decade, however, not much attention was
given to this technique, and it is only in the past 1–2 years
that there has been a resurgence of interest, with multiple
studies showing success rates of 96%–100% (Table1). The
overall complication rate of this technique is less than 2%
and the most dreaded complication is downstream
embolization.18 Samal et al.10 described the technique of
balloon occlusion of the neck of the aneurysm by using a
contralateral approach to prevent spillover of thrombin into
the distal circulation in 4 cases. We in our limited
Table 1. Results from different studies for ultrasoundguided thrombin injection for the obliteration of femoral
artery pseudoaneurysm
Number
of cases
Friedman et al.8
Edgerton et al.9
Samal et al.10
Sheiman et al.11 (Simple)
(Complex)
Paulson et al.12
Kang et al.13
La Perna et al.14
Hughes et al.15
Sievert et al.16
Morrison et al.17
Brophy et al.18
Lennox et al.19
Pezzullo et al.20
Tamim et al.21
Vermeulen et al.22
Taylor et al.23
Wixon et al.24
Liau et al.25
40
47
4
45
9
26
74
70
9
29
39
15
30
23
10
8
29
11
5
11/19/2003, 11:25 PM
Success
(%)
98
94
100
100
56
96
100
94
100
100
100
100
100
96
100
100
93
100
100
Number of
complications
2
1
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
Indian Heart J 2003; 55: 365–367
Goel et al. Thrombin Injection for Femoral Artery Pseudoaneurysm 367
experience, however, found that a transient compression
given to the proximal femoral artery during injection of
thrombin, and confirmation of no flow into the aneurysm
with color/angio mode, may be as good a method to avoid
spillover, which also avoids the need for further invasive
handling of the already damaged site. We do feel, however,
that caution must be exercised with AV fistula and
aneurysm involving bifurcation of the femoral artery as in
such cases a spillover could occur using ultrasound-guided
compression alone. Most failures/recurrences were
observed in patients with complex aneurysms, i.e.
multilobed aneurysms. Other possible complications could
include allergy to bovine thrombin and the formation of a
local abscess formation. Reviewing the literature, the
maximum volume of aneurysmal sac thrombosed by this
technique has been 55 cm3. Our case, on the other hand,
had a giant pseudoaneurysm with a volume of nearly
80 cm3 and was successfully managed using 2000 units
of thrombin, without any complications.
Among the other nonsurgical approaches, it may be
worth mentioning the technique of temporary coil
placement in the pseudoaneurysm sac, described recently
by Trehan et al.26 This technique, however, is more invasive
with a 5 F sheath being placed directly into the aneurysm
sac, and a PDA coil (8 mm) kept in place for over 2 hours
before its final removal. Experience with this technique is
limited to a small aneurysm only.
We conclude that sonographically guided direct
thrombin injection into the aneurysmal sac is a safe, quick,
and effective technique for managing a giant
pseudoaneurysm at the the puncture site. It is well tolerated
by the patient, with low morbidity, and avoids the need for
surgery, and could thus be considered as a first-line therapy
in these patients.
References
1. Zahn R, Thoma S, Fromm E, Lotter R, Zander M, Seidl K, et al.
Pseudoaneurysm after cardiac catheterization: therapeutic
interventions and their sequelae: experience in 86 patients. Cathet
Cardiovasc Diagn 1997; 40: 9–15
2. Chatterjee T, Do DD, Kaufmann U, Maier F, Meier B. Ultrasoundguided compression repair for treatment of femoral artery
pseudoaneurysm: acute and follow-up results. Cathet Cardiovasc Diagn
1996; 38: 335–340
3. Cope C, Zeit R. Coagulation of aneurysm by direct percutaneous
thrombin injection. AJR Am J Roentogenol 1986; 147: 383–387
4. Fellmeth BD, Roberts AC, Bookstein JJ. Postangiographic femoral
artery injuries: nonsurgical repair with US-guided compression.
Radiology 1991; 178: 671–675
5. Agarwal R, Agrawal SK, Roubin GS, Berland L, Cox DA, Iyer SS, et
al. Clinically guided closure of femoral arterial pseudoaneurysms
complicating cardiac catheterization and coronary angioplasty.
Cathet Cardiovasc Diagn 1993; 30: 96–100
6. Dean S, Olin ZW, Piedmonte MA. Ultrasound-guided compression
closure of postcatheterisation pseudoaneurysms during concurrent
IHJ-486-03.p65
367
anticoagulation. J Vasc Surg 1995; 23: 28–35
7. Cox GS, Young JR, Gray BR, Grubb MW, Hertzer NR. Ultrasoundguided compression repair of postcatheterization pseudoaneurysms:
results of treatment in one hundred cases. J Vasc Surg 1994; 19: 683–
686
8. Friedman SG, Pellerito JS, Scher L, Faust G, Burke B, Safa T.
Ultrasound-guided thrombin injection is the treatment of choice for
femoral pseudoaneurysms. Arch Surg 2002; 137: 462–464
9. Edgerton JR, Moore DO, Nichols D, Lane BW, Magee MJ, Dewey TM,
et al. Obliteration of femoral artery pseudoaneurysm by thrombin
injection. Ann Thorac Surg 2002; 74: S1413–S1415
10. Samal AK, White CJ, Collins TJ, Ramee SR, Jenkins JS. Treatment of
femoral artery pseudoaneurysm with percutaneous thrombin
injection. Catheter Cardiovasc Interv 2001; 53: 259–263
11. Sheiman RG, Brophy DP. Treatment of iatrogenic femoral
pseudoaneurysms with percutaneous thrombin injection: experience
in 54 patients. Radiology 2001; 219: 123–127
12. Paulson EK, Sheafor DH, Kliewer MA, Nelson RC, Eisenberg LB,
Sebastian MW, et al. Treatment of iatrogenic femoral arterial
pseudoaneurysms: comparison of US-guided thrombin injection
with compression repair. Radiology 2000; 215: 403–408
13. Kang SS, Labropoulos N, Mansour MA, Michelini M, Filling D, Baubly
MP, et al. Expanded indications for ultrasound-guided thrombin
injection of pseudoaneurysms. J Vasc Surg 2000; 31: 289–298
14. La Perna L, Olin JW, Goines D, Childs MB, Ouriel K. Ultrasound-guided
thrombin injection for the treatment of postcatheterisation
pseudoaneurysms. Circulation. 2000; 102: 2391–2395
15. Hughes MJ, McCall JM, Nott DM, Padley SP. Treatment of iatrogenic
femoral artery pseudoaneurysms using ultrasound-guided injection
of thrombin. Clin Radiol 2000; 55: 749–751
16. Sievert H, Baser A, Pfeil W, Fach A, Scherer D, Spies H, et al. [The
treatment of iatrogenic spurious aneurysm of the femoral artery by
direct thrombin injection.] Dtsch Med Wochenschr 2000; 125: 822–
825
17. Morrison SL, Obrand DA, Steinmetz OK, Montreuil B. Treatment of
femoral artery pseudoaneurysms with percutaneous thrombin
injection. Ann Vasc Surg 2000; 14: 634–639
18. Brophy DP, Sheiman RG, Amatulle P, Akbari CM. Iatrogenic femoral
pseudoaneurysms: thrombin injection after failed US-guided
compression. Radiology 2000; 214: 278–282
19. Lennox AF, Delis KT, Szendro G, Griffin MB, Nicolaides AN, Cheshire
NJ. Duplex-guided thrombin injection for iatrogenic femoral artery
pseudoaneurysm is effective even in anticoagulated patients. Br J
Surg 2000; 87: 796–801
20. Pezzullo JA, Dupuy DE, Cronan JJ. Percutaneous injection of
thrombin for the treatment of pseudoaneurysms after
catheterization: an alternative to sonographically guided
compression. AJR Am J Roentgenol 2000; 175: 1035–1040
21. Tamim WZ, Arbid EJ, Andrews LS, Arous EJ. Percutaneous induced
thrombosis of iatrogenic femoral pseudoaneurysms following
catheterization. Ann Vasc Surg 2000; 14: 254–259
22. Vermeulen EG, Umans U, Rijbroek A, Rauwerda JA. Percutaneous
duplex-guided thrombin injection for treatment of iatrogenic femoral
artery pseudoaneurysms. Eur J Vasc Endovasc Surg 2000; 20: 302–
304
23. Taylor BS, Rhee RY, Muluk S, Trachtenberg J, Walters D, Steed DL, et
al. Thrombin injection versus compression of femoral artery
pseudoaneurysms. J Vasc Surg 1999; 30: 1052–1059
24. Wixon CL, Philpott JM, Bogey WM Jr, Powell CS. Duplex-directed
thrombin injection as a method to treat femoral artery
pseudoaneurysms. J Am Coll Surg 1998; 187: 464–466
25. Liau CS, Ho FM, Chen MF, Lee YT. Treatment of iatrogenic femoral
artery pseudoaneurysm with percutaneous thrombin injection. J
Vasc Surg 1997; 26: 18–23
26. Trehan VK, Mukhopadhyay S, UmaMahesh CR, Yusuf J, Suryavanshi
S, Aora R. Successful closure of iatrogenic femoral artery
pseudoaneurysm: a new minimally invasive technique. Indian Heart
J 2002; 54: 702–704
11/19/2003, 11:25 PM
368 Trehan
et al.
Brief
Report
Stenting of a Septal Perforator Post-MI
Indian Heart J 2003; 55: 368–369
Stenting of a Septal Perforator for Post-Myocardial
Infarction Angina
Vijay Trehan, Saibal Mukhopadhyay, Umamahesh C Rangasetty, Jamal Yusuf, Mohit D Gupta, UA Kaul
Department of Cardiology, GB Pant Hospital, New Delhi
Occlusion of a septal perforator branch alone, without the involvement of the left anterior descending coronary
artery, leading to acute myocardial infarction is unusual. We report a case in which an isolated severely stenotic
thrombus-containing first septal artery causing intractable post-myocardial infarction angina was successfully
dilated and stented. (Indian Heart J 2003; 55: 368–369)
Key Words: Septal artery, Stents, Myocardial infarction
A
cute myocardial infarction (AMI) is usually caused by
the thrombotic occlusion of a major epicardial vessel.
Branch occlusion alone, causing AMI in the absence of
involvement of a major epicardial artery, is unusual. We
report a case in which a patient with anteroseptal
myocardial infarction (MI) and intractable post-MI angina
was found to have isolated 90% obstruction of the first
septal perforator artery, which was successfully dilated and
stented.
Case Report
A 52-year-old male, a known hypertensive on irregular
treatment, presented to us with refractory post-MI angina.
He had had an anteroseptal MI 48 hours earlier for which
he was thrombolized with streptokinase (1.5 million U over
1 hour) within 3 hours of the onset of chest pain. The
patient was taken up for coronary angiography and possible
revascularization. Coronary angiogram revealed a
thrombus-containing 90% discrete stenosis of the first
septal perforator artery just after its origin (Figs 1a and 1b).
The left anterior descending coronary artery (LAD) along
with the other epicardial vessels were normal. The patient
was taken up for angioplasty. He was given a bolus of
abciximab (0.25 mg/kg body weight) followed by an
infusion of 10 µg/min for 12 hours. The lesion in the septal
perforator artery was crossed with a Luge Wire (Boston
Scientific Scimed, Inc., USA), and serially dilated with a
2.5×12 mm and 3×13 mm balloon. Following balloon
Correspondence: Dr Umamahesh C Rangasetty, Department of
Cardiology, GB Pant Hospital, New Delhi 110002.
e-mail: [email protected]
IHJ-442-03.p65
368
dilatation, a check angiogram revealed TIMI 2 flow with
50% residual stenosis. A mounted stent of 3×13 mm (Bx
Velocity, Cordis, USA) was deployed at 14 bars, and
persistent TIMI 3 flow was achieved (Fig. 2). There were no
complications during or after the procedure. The patient
became asymptomatic and was discharged after 72 hours.
On follow-up of nearly a year, the patient is asymptomatic.
Discussion
The interventricular septum (IVS) forms the vital wall for
both the ventricles, and constitutes about one-third of the
total left ventricular (LV) mass.1 The septal perforator
Fig. 1a. Anteroposterior cranial view showing significant eccentric stenosis in
the first septal perforator artery just after its origin.
11/19/2003, 11:24 PM
Indian Heart J 2003; 55: 368–369
Fig. 1b. Left anterior oblique cranial view showing the thrombus in the lesion.
Trehan et al. Stenting of a Septal Perforator Post-MI 369
case reports of isolated septal artery obstruction.3,4 There
have also been reports of angioplasty of the septal
perforators, usually done in patients with critical stenosis
or total occlusion of the LAD.5,6 Recently, there have been a
couple of reports of stenting of a septal perforator artery.
One was in a post-coronary bypass surgery patient with
an occluded LAD,7 while the other was in a patient with
multivessel disease.8 However, to the best of our knowledge,
there have been no reports of angioplasty or stenting of an
isolated culprit septal artery. The first septal perforator,
apart from supplying the IVS, also supplies the bundle of
His, and in 50% hearts, the atrioventricular node.9 Our
patient, with refractory post-MI angina due to occlusion
of the first septal perforator, was at increased risk of
reinfarction that could have disrupted either the conduction
system or the IVS, causing its rupture. Unlike the epicardial
arteries, septal arteries are subjected to a higher extraneous
pressure. Although long-term results of angioplasty of the
septal perforator have not shown increased rates of
restenosis,5 the behavior of stents in response to a high
extrinsic pressure needs to be observed. This situation is
similar to the stenting of myocardial bridges.
References
Fig. 2. Angiographic result following stenting of the septal artery.
branches of the LAD 2 contribute blood supply to the
anterior two-thirds of the IVS. Obstruction of the septal
perforators in patients with diffuse coronary artery disease
is common. However, isolated obstruction of a septal
perforator artery is very rare. Till date, there have been 2
IHJ-442-03.p65
369
1. Kaul S. The interventricular septum in health and disease. Am Heart
J 1986; 112: 568–581
2. Banka VS, Agarwal JB, Bodenheimer MM, Helfant RH.
Interventricular septal motion: biventricular angiographic
assessment of its relative contribution to left and right ventricular
contraction. Circulation 1981; 64: 992–996
3. Nishimura RA, Tajik AJ, Seward JB. Distinctive two dimensional
echocardiographic appearance of septal infarct secondary to isolated
occlusion of first septal perforator artery. Rev Cardiovasc Ultrasound
1984; 1: 97–101
4. Plokker HM, Ernest SM, Van Tellingen C, Bruschke AV. Isolated
obstruction of large septal perforators. Am J Cardiol 1988; 62: 142–
143
5. Vemuri DN, Kochar GS, Maniet AR, Banka VS. Angioplasty of the
septal perforators: acute outcome and long-term clinical efficacy. Am
Heart J 1993; 125: 682–686
6. Comazzi JL, Jang GC, Marsa RJ, Willis WH Jr, Anderson DL, Wareham
EE. Percutaneous transluminal angioplasty of a large septal artery.
Cathet Cardiovasc Diagn 1983; 9: 181–186
7. Ozdemir M, Timurkaynak T, Cemri M, Boyaci B, Yalcin R, Cengel A,
et al. Stenting of the septal perforator coronary artery. J Invasive
Cardiol 2001; 13: 694–697
8. Regar E, Kozuma K, Ligthart J, et al. Coronary stent implantation in
septal perforator artery. Jpn Circ J 2000; 64: 802–804
9. Pujadas G (ed). Coronary angiography. New York: McGraw-Hill Book
Company, Inc. 1980; p. 72
11/19/2003, 11:24 PM
370 Bedi
et al.
Brief
Report
Indian Heart J 2003; 55: 370–372
MV Replacement on a Beating Heart
Mitral Valve Replacement on a Beating Heart
Harinder S Bedi, Raman P Singh, Vipin Goel, Purshottam Lal
Metro Heart Institute, Noida
We report the case of a patient who needed mitral valve replacement but was at a high risk of myocardial injury
with the conventional technique (cardioplegic arrest on cardiopulmonary bypass). Valve replacement was carried
out on a beating heart on cardiopulmonary bypass by perfusing the heart continuously with oxygenated
noncardioplegic normothermic blood via the coronary sinus. (Indian Heart J 2003; 55: 370–372)
Key Words: Mitral valve replacement, Cardiopulmonary bypass, Beating heart
C
ardioplegic techniques carry with them the almost
obligatory sequel of some degree of reperfusion injury.1
Any technique that avoids the ischemic component of
cardioplegia and an arrested heart by keeping the heart
beating will go a long way in reducing iatrogenic damage
to the heart. While the heart–lung machine can be avoided
in most cases of coronary artery bypass grafting (CABG),2
it is still mandatory in open heart valvular surgery. We
present a case of a high-risk mitral valve operation
performed on a beating heart.
Case Report
A 15-year-old girl presented with orthopnea and congestive
heart failure. She was a known case of rheumatic heart
disease with severe mitral regurgitation, moderate mitral
stenosis, severe pulmonary artery hypertension, and severe
functional tricuspid regurgitation. The diagnosis was
confirmed by echocardiography. She did not show much
improvement with aggressive medical therapy, and was
taken up for emergency surgery. Since she would have been
at a high risk of reperfusion injury if standard techniques
of cardioplegic arrest were used, a technique of on-pump
beating heart surgery was planned.
The operation was performed through a median
sternotomy. After heparinization, total cardiopulmonary
bypass (CPB) was established by aortic and bicaval
cannulation. The patient was actively warmed to 36.5°C,
and pulsatile flow maintained at the highest pressure that
was safely possible, keeping the mean systemic pressure
Correspondence: Dr Harinder Singh Bedi, Chief Cardiac Surgeon and
Chairman, Cardio-Vascular Surgery, Metro Heart Institute, X-1, Sector 12,
Noida, NCR, Delhi. e-mail: [email protected]; [email protected]
IHJ-492-03.p65
370
above 60 mmHg. The pump flow was kept at 2.5 L/min/m2,
and the FiO2 was kept at 100%.
A retrograde self-inflating coronary sinus cannula
(Medtronic DLP, Grand Rapids, MI) was inserted by a
standard closed technique. The position was confirmed by
palpation, and the balloon positioned as close to the
coronary sinus ostium as possible to avoid right ventricular
malperfusion. The central perfusion port was connected to
the standard cardioplegic line circuit, and oxygenated
unmodified (noncardioplegic) blood primed into the
cannula. With an aortic root vent and maximal venous
drainage, retrograde perfusion was started, and
simultaneously the aorta was cross-clamped. Retrograde
perfusion flow was maintained at 250–300 ml/min with
constant monitoring of the intracoronary sinus pressure
via its integral pressure line, keeping a mean coronary sinus
pressure of 40 mmHg. A phosphodiesterase inhibitor—
milrinone 0.5 µg/kg/min—was infused in the retrograde
line by a syringe pump to increase the retrograde perfusion
flow by inducing vasodilatation. Samples of the blood
entering the coronary sinus and of the blood in the aortic
root vent were taken for analysis and calculation of the
oxygen extraction ratio across the myocardium.3 The left
atrium was now opened and mitral valve replacement with
preservation of the posterior mitral apparatus carried out
on the beating heart (Figs 1 and 2). At the end of the
procedure, the cardiac cavities were filled with blood (by
inflating the lungs) and with warm saline, and the left
atrium was closed. The aortic root vent was kept on suction,
the aortic cross-clamp released, and the retrograde coronary
sinus cannula removed. The right atrium was opened, and a
standard repair (DeVega annuloplasty) of the tricuspid valve
carried out.
11/19/2003, 11:25 PM
Indian Heart J 2003; 55: 370–372
Bedi et al. MV Replacement on a Beating Heart 371
O2AR: O2 content of blood from the aortic root;
O2A: O2 content (arterial).
[O2 content = 1.36 ml O2 /g × Hb × O2 saturation + (0.003 × pO2)]
Fig. 1. A line diagram showing the operative technique. ACC: aortic cross-clamp;
IVC: cannula in the inferior vena cava; MV: prosthetic mitral valve; R: retrograde
coronary sinus cannula; SVC: cannula in the superior vena cava; V: aortic root
vent
The high extraction is suggestive of the fact that the
myocardium uses up the oxygen being delivered by the
retrograde route.
The CPB time was 98 min while the aortic cross-clamp
time was 52 min. The heart continued to be in sinus rhythm
during and after the procedure. There was no evidence of
ischemia—no ST segment changes and no rhythm
disturbance occurred during the retrograde perfusion. The
patient was weaned away from CPB without any inotropic
support, and was extubated within 5 hours of reaching the
ICU. She made an uneventful recovery, and was discharged
on postoperative day 6.
Discussion
Fig. 2. A photograph taken during surgery. ACC: aortic cross-clamp; SVC:
cannula in the superior vena cava; MV: prosthetic mitral valve; IVC: cannula in
the inferior vena cava; V: aortic root vent; R: retrograde coronary sinus cannula
Good visualization of the mitral valve apparatus was
possible, and the procedure was completed without any
technical difficulty. Despite the motion of the heart, the onpump and totally decompressed state of the heart caused
by cardiac venting resulted in a good quality of the visual
field, equaling that of the conventional technique, and
technical accuracy was not affected.
An oxygen extraction ratio of 52% across the myocardium was noted:
Oxygen extraction ratio across the myocardium =
O2CS– O2AR
_________________
× 100
O2A
where, O2CS: arterial O2 content (i.e. going into the coronary
sinus);
IHJ-492-03.p65
371
In spite of improvements in myocardial protection
techniques, some perioperative adverse effects of
myocardial ischemia caused by aortic cross-clamping,
cardioplegia, and reperfusion remain. Even with
continuous warm blood cardioplegia (considered by some
as the best form of myocardial protection as it keeps the
heart in an aerobic state), some degree of perioperative
myocardial stunning still occurrs.1 Cardiac dysfunction
may be caused by myocardial edema intrinsic to the
diastolic state of the arrested heart,4 and the inevitable
reperfusion injury that follows the unclamping of the
arrested heart. Ischemia followed by reperfusion is
invariably followed by the generation of oxygen-free
radicals, which produce myocardial injury. To counter this,
various scavengers of oxygen-free radicals have been added
to cardioplegic solutions in an attempt to inhibit the
injury. 5,6 Keeping the heart beating results in less
myocardial edema, and better cardiac function.4
Retrograde coronary sinus perfusion as a method of
myocardial perfusion is not new. In 1956, Lillehei et al.7
reported an aortic valve replacement using coronary sinus
perfusion at 125 ml/min. Oxygenated blood is perfused
from the coronary sinus and reaches the myocardium via
the coronary venous system and the capillaries, and goes
out via the arterial end as in retrograde cardioplegia. We
have previously used retrograde perfusion on the beating
heart to perform CABG without CPB.2,3 The technique of
beating heart valve surgery involves the constant
retrograde perfusion of pure normothermic oxygenated
blood into the coronary sinus.
Matsumoto et al.8 recently performed a beating heart
11/19/2003, 11:25 PM
372 Bedi et al. MV Replacement on a Beating Heart
valve procedure on 25 patients with good results. They
showed, by intraoperative monitoring, that myocardial
tissue oxygen saturation (SO2) levels were maintained at
the preoperative physiologic values throughout the
procedure. A good myocardial oxygen consumption, as
noted by us, indicates that the myocardium is in a state of
aerobic metabolism that is maintained by the retrograde
coronary sinus perfusion.
The advantages of the technique are: a perfused beating
heart that does not have to ‘‘work’’ (pump blood); no
reperfusion injury (as there is no ischemia); an
uninterrupted performance of the operation; a long period
of continuous oxygenated blood delivery that maintains the
beating of the heart; appropriate pH, effective delivery of
substrates, and removal of acid metabolites; more uniform
oxygenated blood distribution in the presence of any
associated coronary artery stenosis; testing of the mitral
valve repair, when performed, can be done under the actual
physiologic conditions of a normal left ventricular tone with
preserved three-dimensional architecture of the beating
heart (with conventional techniques, the mitral valve is in
a motionless flaccid state that may not accurately reflect
its function in the beating heart); avoidance of injury to
the ostia of the coronary arteries; and the possibility of
performing ablation for atrial fibrillation on the beating
heart. The normothermic state of the blood ensures
maximal vasodilatation of the cardiac veins, and steady,
uniform flow and distribution. Should the flow be
inadequate or if there is malperfusion, it will be reflected
by ECG changes (ST segment changes, bradycardia,
arrhythmias, etc.), and the flow can be suitably adjusted.
The option of converting to the conventional technique—
cardiac arrest with hyperkalemic blood cardioplegia— is
always immediately available, if the surgeon is not satisfied
IHJ-492-03.p65
372
Indian Heart J 2003; 55: 370–372
with the beating heart technique.
The beating heart technique is thus a useful addition to
the armamentarium of the cardiac surgeon in dealing with
patients undergoing high-risk valve surgery. A comparison
of this procedure versus the arrested heart technique in a
large group of patients is required to judge the superiority
of the beating heart technique.
References
1. Misare BD, Krukenkamp IB, Lazer ZP, Levitsky S. Recovery of
postischemic contractile function is depressed by antegrade warm
continuous blood cardioplegia. J Thorac Cardiovasc Surg 1993; 105:
37–44
2. Bedi HS, Suri A, Kalkat MS, Sengar BS, Mahajan V, Chawla R, et al.
Global myocardial revascularization without cardiopulmonary
bypass using innovative techniques for myocardial stabilization and
perfusion. Ann Thorac Surg 2000; 69: 156–164
3. Bedi HS. Selective graft and coronary sinus perfusion in off pump
CABG: is it necessary? [Reply]. Ann Thorac Surg 2001; 71: 1070–
1072
4. Mehlhorn U, Allen SJ, Adamus DL, Davis KL, Gogola GR, Warters
RD. Cardiac surgical conditions induced by beta blockade: effect on
myocardial fluid balance. Ann Thorac Surg 1996; 62: 143–150
5. Vinten-Johansen J, Ronson RS, Thourani VH, Wechsler AS. Surgical
myocardial protection. In: Gravlee GP, Davis RF, Kurusz M, Utley JR
(eds). Cardiopulmonary bypass—principles and practice. 2nd ed.
Phliladelphia: Lippincott Williams and Wilkins; 2000. p. 214
6. Kirklin JW, Barratt-Boyes BG. Myocardial management during
cardiac surgery with cardiopulmonary bypass. In: Kirklin JW,
Barratt-Boyes BG (eds). Cardiac surgery. Morphology, diagnostic criteria,
natural history, techniques, results and indications. 2nd ed. New York:
Churchill Livingstone; 1993. p. 129
7. Lillehei CW, DeWall RA, Gott VL, Varco RL. The direct vision
correction of calcific aortic stenosis by means of a pump oxygenator
and retrograde coronary sinus perfusion. Dis Chest 1956; 30:
123–131
8. Matsumoto Y, Watanabe G, Endo M, Sasaki H, Kasashima F, Kosugi
I. Efficacy and safety of on-pump beating heart surgery for valvular
disease. Ann Thorac Surg 2002; 74: 678–683
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Radha et al. Catheter Elimination of Accessory Pulmonary Blood
373
BriefFlow
Report
Transcatheter Closure of Native Pulmonary Artery for the
Elimination of Accessory Pulmonary Blood Flow After
Bidirectional Glenn Shunt
Anil Sivadasan Radha, Bhava RJ Kannan, Raman Krishna Kumar
Division of Pediatric Cardiology, Amrita Institute of Medical Sciences and Research Centre, Kochi
We report a case where excessive accessory pulmonary blood flow via the native pulmonary valve after
cavopulmonary anastomosis resulted in pulmonary hypertension and heart failure. This flow was successfully
eliminated in the cardiac catheterization laboratory using an Amplazter duct occluder that was placed across
the native pulmonary valve. (Indian Heart J 2003; 55: 373–375)
Key Words: Catheter intervention, Amplatzer duct occluder, Cavopulmonary shunt
B
idirectional Glenn shunt (BDGS) is frequently
performed as part of a multistaged palliation of
congenital heart disease in patients with a single ventricle
physiology to decrease the volume overload in patients who
are candidates for future Fontan type repair.1,2 It is often
advocated as an intermediary step for high-risk patients.3
Traditionally, accessory sources of pulmonary blood flow,
such as from the native pulmonary valve, are eliminated
to minimize pulmonary artery (PA) pressure after
cavopulmonary anastomosis (Glenn shunt). Recently,
however, there is a growing trend towards preservation of
blood flow through the native pulmonary valve to improve
saturation. However, occasionally patients can develop
heart failure when blood flow through the native
pulmonary valve is excessive. We report a child who
presented with elevated PA pressures due to excessive
antegrade pulmonary blood flow after a Glenn shunt and
the successful interruption of this additional flow using an
Amplatzer duct occluder (ADO).
Case Report
The patient was an 11-year-old boy with severe cyanosis
(basal saturation of 65%) and marked limitation of physical
activity. The anatomic diagnosis was situs solitus, D-loop,
levocardia, bilateral superior vena cava (SVC), double outlet
right ventricle, multiple muscular ventricular septal defects
Correspondence: Dr R Krishna Kumar, Division of Pediatric Cardiology,
Amrita Institute of Medical Sciences and Research Centre, Elamakkara PO,
Kochi 682026. e-mail: [email protected]
IHJ-502-03.p65
373
(VSDs), and severe infundibular and valvar pulmonic
stenosis. At the age of 3 years, the child underwent atrial
septectomy with Brock procedure (enlargement of right
ventricular outflow in relation to the pulmonary valve).
Cardiac catheterization at admission showed elevated right
atrial (mean: 18 mmHg) and PA pressures (29/17 mmHg,
mean: 23 mmHg) with a pulmonary-to-systemic blood flow
ratio of 3:1, and the calculated indexed pulmonary vascular
resistance was 0.14 Wood units/m2. He underwent rightsided cavopulmonary anastomosis with ligation of the left
SVC and enlargement of the atrial septal defect. Ligation
of the PA could not be done as planned due to dense
adhesions in the region of the main pulmonary artery
(MPA). His immediate postoperative course was uneventful.
On postoperative day 11, it was noticed that he had
prominent neck vein pulsations, and prominent chest wall
veins, which were seen to drain from above downwards.
Besides, he had an overt right heart failure with ascites and
hepatomegaly. Echocardiography showed systolic
retrograde pulsatile flow in the right SVC due to excessive
antegrade flow from the right ventricle into the PA.
Informed consent was taken and cardiac catheterization
was performed under conscious sedation. The femoral
vessels and the right subclavian vein were cannulated
percutaneously. The SVC pressure tracing showed a
biphasic wave pattern and was markedly elevated (38/18
mmHg, mean 26 mmHg). The PA angiogram showed
normal branch pulmonary arteries with rapid wash-off of
the contrast, and the PA annulus measured 12.5 mm. The
pulmonary valve was crossed in a retrograde fashion with
a 0.035" exchange length (300 cm) Roadrunner wire
11/19/2003, 11:25 PM
374 Radha et al. Catheter Elimination of Accessory Pulmonary Blood Flow
Fig. 1. Temporary balloon occlusion: a veno-venous loop has been formed from
the right superior vena cava to the femoral vein. A 7F Swan–Ganz catheter has
been passed from the femoral vein, and the balloon of this catheter has been
inflated in the main pulmonary artery to temporarily occlude antegrade flows.
A hand injection has been made through the sheath passed via the right subclavian
vein. RPA: right pulmonary artery; LPA: left pulmonary artery.
Indian Heart J 2003; 55: 373–375
Fig. 2. A hand injection via the side arm of the sheath, just prior to the release
of the device, shows the position of the device (Amplatzer duct occluder [ADO]).
years. He had a resting saturation of 88% and was
symptom-free.
Discussion
(Cook Inc.) and Judkins Right 4 catheter (Cook Inc.). The
wire was snared with a 10 mm Amplatz gooseneck snare
(Microvena Corp., MN, USA), and was brought out of the
left femoral venous sheath to form a veno-venous wire loop.
A 7 F Swan–Ganz catheter was passed over the wire from
the groin and the balloon at the tip of the catheter was
inflated (Fig.1) to occlude the MPA. The PA pressures on
balloon occlusion decreased to 25/14 mmHg (mean: 17
mmHg) without any fall in aortic saturation. A 9 F long
sheath (Cook Inc., Bloomington, IN, USA) was introduced
from the subclavian vein and across the pulmonary valve
into the right ventricular outflow tract. A 16/14 ADO
(AGA Medical, MN, USA) device was advanced through the
sheath, and a small part of the retention disc was extruded
from the sheath into the ventricle just below the valve and
then pulled against the pulmonary valve. The device was
deployed such that the waist straddled the pulmonary valve
(Fig. 2). Gentle pulling and pushing of the device under
echocardiographic and fluoroscopic guidance was done to
ensure stability of the device. The device was released after
confirming that the flow across the cavopulmonary
anastomosis was unobstructed. The patient recovered
uneventfully. Three months later, he had gained weight
(2.5 kg) and restarted attending his school after a gap of 2
IHJ-502-03.p65
374
Cavopulmonary anastomosis is used as an intermediary
stage prior to completion of a Fontan type of repair in those
with a single ventricle physiology.1–3 It is controversial
whether an additional source of systemic-to-pulmonary
artery flow is beneficial.3–5 In some instances, it is thought
to improve oxygenation, decrease the incidence of
pulmonary arteriovenous fistula formation, and promote
the growth of the pulmonary arteries.3,4 However, it may
result in elevation of the SVC pressure, with interference
of the blood flow to the pulmonary arteries. Additionally,
depending on its magnitude, it may add an additional
volume load on the left ventricle. In our patient, the SVC
pressure was markedly elevated. The pressure tracing prior
to closure was suggestive of pulsatile flows. Temporary
balloon occlusion of the MPA resulted in a substantial
decrease in the SVC pressures and eliminated venous
pulsatility. This conclusively showed that excessive
pulmonary blood flow through the native pulmonary valve
was responsible for the adverse hemodynamics.
Even though the ADO is conventionally used for closure
of a patent ductus arteriosus, it was well suited for this
purpose, as its flat retention disc allows positioning of the
device without interfering with the flow through the Glenn
anastomosis.6,7 It allows easy testing of the stability of the
11/19/2003, 11:26 PM
Indian Heart J 2003; 55: 373–375
Radha et al. Catheter Elimination of Accessory Pulmonary Blood Flow 375
device before release. We chose an oversized duct occluder
instead of a muscular VSD occluder because it is less
expensive. The precise positioning of the device such that
it straddles the pulmonary valve is critical. If the device is
too far into the ventricle, it could slip down and get
embolized through the systemic circuit. If the device is
placed entirely distal to the pulmonary valve, it can migrate
distally and can occlude the branch pulmonary arteries.
Because of the absence of a retention disc on the pulmonary
arterial aspect, we chose to oversize the device substantially.
Conclusions: This report demonstrates the
unconventional use of an ADO for occlusion of the native
pulmonary valve. This offers an easy and nonsurgical
solution in this subset of patients who would otherwise
need repeat surgical procedures. Temporary balloon
occlusion is a useful maneuver to ascertain the contribution
of accessory pulmonary blood flow so that the benefits of
eliminating this flow can be predicted.
IHJ-502-03.p65
375
References
1. Mazzera E, Corno A, Picardo S, Di Donato R, Marino B, Costa D, et al.
Bidirectional cavopulmonary shunts: clinical applications as staged
or definitive palliation. Ann Thorac Surg 1989; 47: 415–420
2. Allgood NL, Alejos J, Drinkwater DC, Laks H, Williams RG.
Effectiveness of the bidirectional Glenn shunt procedure for volume
unloading in the single ventricle patient. Am J Cardiol 1994; 74:
834–836
3. Masuda M, Kado H, Shiokawa Y, Fukae K, Suzuki M, Murakami E, et
al. Clinical results of the staged Fontan procedure in high-risk
patients. Ann Thorac Surg 1998; 65: 1721–1725
4. Mainwaring RD, Lamberti JJ, Uzark K, Spicer RL. Bidirectional Glenn.
Is accessory pulmonary blood flow good or bad? Circulation 1995;
92 (Suppl 9): II294–II297
5. Migliavacca F, de Leval MR, Dubini G, Pietrabissa R. A computational
pulsatile model of the bi-directional cavopulmonary anastomosis:
the influence of pulmonary forward flow. J Biomech Engineer 1996;
11: 520–528
6. Masura J, Walsh KP, Thanopoulous B, Chan C, Bass J, Goussous Y, et
al. Catheter closure of moderate- to large-sized patent ductus
arteriosus using the new Amplatzer duct occluder: immediate and
short-term results. J Am Coll Cardiol 1998; 31: 878–882
7. Ebeid MR, Masura J, Hijazi ZM. Early experience with the Amplatzer
ductal occluder for closure of the persistently patent ductus
arteriosus. J Interv Cardiol 2001; 14: 33–36
11/19/2003, 11:26 PM
376 Singh
et al.
Brief
Report
LA–CS Dissociation After RFA for AP
Indian Heart J 2003; 55: 376–378
Left Atrial–Coronary Sinus Dissociation Following an
Attempt at Radiofrequency Ablation for a Left Lateral
Accessory Pathway
Balbir Singh, Rakesh Sapra, Ripen K Gupta, Tapan Ghose, Rahul Trehan, Upendra Kaul
Department of Cardiology, Batra Hospital and Medical Research Centre, New Delhi
Coronary sinus electrograms generally represent the sequence of left atrial activation, and are very helpful in
localizing and differentiating left lateral accessory pathway-mediated tachycardia from other supraventricular
tachycardias. The activation of the coronary sinus from the left atrium occurs through muscle bridges, which
may be discrete or form an intermingled continuum. These muscle bridges, if disconnected, may dissociate the
coronary sinus from the left atrium, in which case the coronary sinus electrograms do not represent left atrial
activation, and do not help to understand, or may cause misinterpretation of, the mechanism of supraventricular
tachycardia. We report one such case of orthodromic supraventricular tachycardia mediated through the left
lateral accessory pathway in which the coronary sinus got dissociated from the left atrium during radiofrequency
ablation. (Indian Heart J 2003; 55: 376–378)
Key Words: Left lateral accessory pathway, Coronary sinus, Radiofrequency ablation
R
adiofrequency (RF) ablation for accessory pathways
(APs) is safe and effective.1,2 The mapping of APs
involves the use of multipolar electrodes placed at different
sites. Coronary sinus (CS) electrograms assume an
important role (particularly for left-sided pathways), and
generally represent the sequence of left atrial (LA)
activation.3 We report a case of an orthodromic tachycardia
using a concealed left lateral AP in which the activation
sequence in CS electrograms reversed following an attempt
at RF ablation without altering the AP conduction.
Case Report
A 23-year-old man was referred to our institute for
recurrent episodes of supraventricular tachycardia (SVT)
lasting for several hours. He was taken up for an
electrophysiologic study and possible ablation. The AH
interval was 110 ms while the HV interval was 45 ms.
Retrograde conduction on ventricular pacing was eccentric,
with earliest activation at the distal CS (Fig. 1a). An SVT
with a cycle length (CL) of 330 ms could easily be induced
Correspondence: Dr Balbir Singh, Senior Consultant, Interventional
Cardiology and Cardiac Electrophysiology, Batra Hospital and Medical Research
Centre, 1, Tughlakabad Institutional Area, Mehrauli Badarpur Road, New Delhi
110062.
IHJ-409-02.p65
376
with a single atrial extrastimulus, with a retrograde atrial
activation sequence similar to that during ventricular
pacing (Fig. 1b).
After a trans-septal puncture, a 7 F ablation catheter
(Cordis Webster) was introduced to map the left free wall
AP along the lateral mitral annulus. During ventricular
pacing, a site with the shortest VA interval preceding all
other atrial activations was chosen for the application of
RF energy (Fig. 2). During the RF application, it was realized
that the retrograde activation sequence had changed to one
resembling concentric activation (Fig. 3a).
The RF lesion was completed after 60 s, and the
stimulation protocols repeated. An SVT could be induced
again but with a different activation sequence (proximal to
the distal CS sequence, and earliest activation at the His
bundle site) (Fig. 3b). On observing this change in the atrial
activation sequence, this tachycardia was thought to be
either an atypical atrioventricular nodal re-entrant
tachycardia or a slow conducting anteroseptal AP. A
diagnosis of ectopic atrial tachycardia was excluded by
overdrive pacing from the right ventricle. This resulted in
entrainment of the tachycardia with the same atrial
sequence and, on abrupt termination of pacing, the return
sequence was an A–V electrogram favoring re-entry rather
than atrial tachycardia.4 However, on mapping with the
ablation catheter around the mitral annulus, it was soon
11/19/2003, 11:24 PM
Indian Heart J 2003; 55: 376–378
b
a
Fig. 1. Intracardiac recording during ventricular pacing (a) and following the
induction of supraventricular tachycardia (b). The earliest retrograde atrial
activation is in the distal coronary sinus recordings. HRA: high right atrium;
HBp: His bundle-proximal; HBd: His bundle-distal; PCS: proximal coronary
sinus; MCS: mid-coronary sinus; DCS: distal coronary sinus
Singh et al. LA–CS Dissociation After RFA for AP 377
a
b
Fig. 3. Intracardiac recording showing that the retrograde activation sequence
during ventricular pacing (a) and supraventricular tachycardia (b) following
the RF lesion has changed to a concentric activation sequence with earliest
activation at the site of the bundle of His followed by PCS, MCS, and DCS. PCS:
proximal coronary sinus; MCS: mid-coronary sinus; DCS: distal coronary sinus;
HRA: high right atrium; HBp: His bundle-proximal; HBd: His bundle-distal;
RVA: right ventricular apex
Fig. 2. Intracardiac recordings obtained from a 7 F ablation catheter placed at
the lateral mitral annulus (MAP) following trans-septal puncture. The VA
interval here is the shortest compared to all the other recordings. HRA: high
right atrium; HBp: His bundle-proximal; HBd: His bundle-distal; PCS: proximal
coronary sinus; MCS: mid-coronary sinus; DCS: distal coronary sinus
realized that the shortest VA interval was still around the
lateral mitral annulus with the CS electrograms not truly
reflecting the activation sequence in the LA (Fig. 4).
Delivering another RF pulse at this site, which was slightly
more anterior to the previous site, resulted in termination
of the tachycardia with a retrograde conduction block.
Subsequent ventricular pacing demonstrated a compete VA
block (Fig. 5), and no tachycardia could be induced despite
isoprenaline infusion, and multiple atrial and ventricular
extrastimuli.
IHJ-409-02.p65
377
Fig. 4. Intracardiac recording showing the shortest VA interval in the mapping
catheter at the lateral mitral annulus. HBp: His bundle-proximal; PCS: proximal
coronary sinus; MCS: mid-coronary sinus; DCS: distal coronary sinus; HRA:
high right atrium; MAP: lateral mitral annulus
Discussion
The diagnosis of an orthodromic tachycardia using a lateral
concealed AP was confirmed by the earliest retrograde
activation sequence recorded at the distal CS during the
tachycardia. This was similar to the atrial activation pattern
during ventricular pacing. During the RF pulse, the change
in the atrial activation sequence from an eccentric to a
11/19/2003, 11:24 PM
378 Singh et al. LA–CS Dissociation After RFA for AP
Fig. 5. Ventricular pacing following the ablation (at the site on the lateral mitral
annulus as shown in Fig. 4) shows complete VA dissociation. HBp: His bundleproximal; PCS: proximal coronary sinus; MCS: mid-coronary sinus; DCS: distal
coronary sinus; MAPp: lateral mitral annulus-proximal; MAPd: lateral mitral
annulus-distal
concentric sequence during ventricular pacing made us
believe that the AP had been eliminated. However, when
SVT could easily be induced thereafter, careful mapping was
performed to understand the mechanism of this “new”
tachycardia. The mapping at the lateral mitral annulus
clearly demonstrated that this was the same orthodromic
tachycardia but with an altered sequence of activation in
the CS electrograms. The atrial signal on the ablation
catheter preceded the atrial recording on the His bundle
and proximal CS recordings (Fig. 4). Therefore, atrial
activation was not concentric (as suggested by CS and His
bundle recordings). This was confirmed by the fact that an
RF pulse at this site resulted in the termination of SVT with
a retrograde block, after which a VA block was
demonstrated, and the SVT could not be reinitiated. This
change in epicardial (CS) sequence without a change in
endocardial activation probably resulted from the initial RF
pulse, which could have caused a dissociation between the
LA and CS. Recent histologic studies have demonstrated
that the lumen of the CS contains myocardium that is
continuous with CS ostial–right atrial myocardium.5,6 The
proximal CS is separated from the LA by adipose tissue,
while the rest of the CS has discrete muscle bridges
connecting these two structures. Considerable variations
IHJ-409-02.p65
378
Indian Heart J 2003; 55: 376–378
are known, ranging from 1 to 2 fascicles to intermingled
continuum.4 It is possible that there was a discrete bridge
connecting the LA to the distal CS in this patient, which
got disconnected following the initial RF pulse, and resulted
in a change of sequence without a change in the
mechanism of the tachycardia.
CS recordings generally represent LA activation. It is,
however, important to understand the complex histology
and interconnections between the LA and CS. The example
in this report represents the disconnection between the LA
and CS following the initial RF pulse. Chauvin et al. 6
recently demonstrated an electrical dissociation between
the CS and LA in a group of patients with atrial flutter and
atrial fibrillation. In a series of 159 patients, Luria et al.7
discussed an intra-atrial conduction block along the mitral
annulus during AP ablation. Alberte et al. 8 and
Vasconcecos et al.9 have described a case each in which
dissociation quite similar to the present report occurred
following an attempt at ablation of the lateral AP. It is
important to understand these mechanisms since an
inability to recognize the dissociation could have resulted
in the erroneous diagnosis of a second tachycardia leading
to inappropriate treatment.
References
1. Jackman WM, Wang XZ, Friday KJ, Roman CA, Moulton KP,
Beckman KJ, et al. Catheter ablation of accessory atrioventricular
pathways (Wolff–Parkinson–White syndrome) by radiofrequency
current. N Engl J Med 1991; 324: 1605–1611
2. Calkins H, Langberg J, Sousa J, el-Atassi R, Leon A, Kou W, et al.
Radiofrequency catheter ablation of accessory atrioventricular
connections in 250 patients. Abbreviated therapeutic approach to
Wolff–Parkinson–White syndrome. Circulation 1992; 85: 1337–
1346
3. Kuck KH, Schluter M, Geiger M, Siebels J, Duckeck W. Radiofrequency
current catheter ablation of accessory atrioventricular pathways.
Lancet 1991; 337: 1557–1561
4. Knight BP, Zivin A, Souza J, Flemming M, Pelosi F, Goyal R, et al. A
technique for the rapid diagnosis of atrial tachycardia in the
electrophysiology laboratory. J Am Coll Cardiol 1999; 33: 775–781
5. Antz M, Otomo K, Arruda M, Scherlag BJ, Pitha J, Tondo C, et al.
Electrical conduction between the right atrium and the left atrium
via the musculature of the coronary sinus. Circulation 1998; 98:
1790–1795
6. Chauvin M, Shah DC, Haíssaguerre M. The anatomic basis of
connections between the coronary sinus musculature and the left
atrium in humans. Circulation 2000; 101: 647–652
7. Luria DM, Nemec J, Etheridge SP, Compton SJ, Klein RC, Chugh SS,
et al. Intra-atrial conduction block along the mitral valve annulus
during accessory pathway ablation: evidence for a left atrial
“isthmus”. J Cardiovasc Electrophysiol 2001; 12: 744–749
8. Alberte C, Hadian D, Miller JM, Olgin JE. A changing tachycardia
that did not change. J Cardiovasc Electrophysiol 2002; 13: 727–729
9. Vasconcecos JTM, Costa ERB, Galvaofilho SDS. Block of the mitral–
pulmonary isthmus during ablation of a single left-sided accessory
pathway causing different patterns of retrograde atrial activation.
Arq Bras Cardiol 2002; 78: 504–509
11/19/2003, 11:24 PM
Indian Heart
J 2003; 55: 379–381
Brief
Report
Chockalingam et al. Left Atrial Appendage Aneurysm 379
Massive Left Atrial Appendage Aneurysm Presenting as
Supraventricular Tachycardia
Anand Chockalingam, R Alagesan, M Nandakumar, G Gnanavelu
Department of Cardiology, Madras Medical College and Research Institute, Chennai
Left atrial appendage aneurysm is a rarely reported condition. Symptoms are absent in childhood and diagnosis
is usually incidental. Systemic embolization or arrhythmia can bring these cases to medical attention. We report
the case of a 12-year-old male with massive left atrial appendage aneurysm who presented with effort intolerance
and supraventricular arrhythmia. The diagnosis was made by transthoracic echocardiography. Magnetic
resonance imaging and left atriogram were also done before surgical resection. (Indian Heart J 2003; 55:
379–381)
Key Words: Left atrial appendage, Supraventricular tachycardia, Echocardiography
L
eft atrial appendage (LAA) aneurysm is a rarely
encountered congenital defect. Most LAA aneurysms
are diagnosed incidentally. They can result in arrhythmias
or systemic embolization.1 We report a child with massive
LAA aneurysm who presented with effort intolerance and
arrhythmias.
Case Report
A previously healthy 12-year-old boy presented with a
6-month history of effort intolerance, retrosternal pricking
type of chest discomfort, and palpitations. His NYHA
functional status had progressed to class III. The pulse,
blood pressure, and jugular venous pressure were normal.
His cardiac examination revealed normal apical impulse
in the left 5th intercostal space. Heart sounds were normal
without murmurs or gallops. The initial electrocardiogram
(ECG) was normal, and when repeated during palpitations,
showed narrow QRS nodal re-entrant tachycardia at a rate
of 235/min.
Chest X-ray PA view showed cardiomegaly with a CT
ratio of 64% with straightening of the left heart border. It
showed filling out of the cardiac bay (Fig. 1). The lateral
view X-ray confirmed that the enlarged chamber was the
left atrium (LA). Lung markings were unremarkable.
Transthoracic echocardiography revealed a very large
(15×10 cm) echo-free space compressing the left ventricle
Correspondence: Dr Anand Chockalingam, Madras Medical College and
Research Institute, 9 A Taylors Road, Kilpauk, Chennai 600010.
e-mail: [email protected]
IHJ-547-03.p65
379
(Figs 2, 3). The chamber connected to the LA in the region
of the LAA. Autocontrast was present within the LAA
aneurysm due to sluggish flow (Fig. 2). To-and-fro blood
flow was demonstrated using Doppler echo (Fig. 3). The
relative size and location of the aneurysm was delineated
by magnetic resonance imaging (MRI) (Fig. 4). Cardiac
catheterization confirmed normal chamber pressures and
saturations. The LA injection by trans-septal puncture
opacified a large chamber adjacent to the left heart (Fig. 5).
The patient was operated on cardiopulmonary bypass.
The aneurysm was resected and the histopathology report
confirmed benign cardiac and fibrous tissue. His symptoms
improved rapidly and he is now doing well 10 months after
the resection without recurrence of palpitation.
Fig. 1. Chest X-ray in posteroanterior view showing filling out of the cardiac
bay, altering the left cardiac border.
11/19/2003, 11:26 PM
380 Chockalingam et al. Left Atrial Appendage Aneurysm
Fig. 2. Transthoracic echocardiogram in apical 4-chamber view showing the
massive left atrial appendage (LAA) aneurysm from the left atrium (LA).
Autocontrast is seen within the LAA aneurysm. The left ventricle (LV) is
compressed by the LAA aneurysm, while the right atrium (RA) and right
ventricle (RV) are normal.
Indian Heart J 2003; 55: 379–381
Fig. 4. MRI in sagittal section clearly defining the extent and relations of the
left atrial appendage (LAA) aneurysm.
Fig. 3. Transthoracic echocardiogram in modified parasternal short-axis view
showing massive left atrial appendage (LAA) aneurysm arising from the left
atrium (LA) in the region of LAA. The aortic (AO) valve is seen in cross-section.
Discussion
Aneurysm of the LAA can be secondary to left ventricular
dysfunction, mitral valve pathology, or herniation of the
LAA through a pericardial defect.1,2 Primary congenital
aneurysm of the LAA with an intact pericardium is a rare
anomaly.1–3 Intrapericardial LAA aneurysm is due to
congenital weakness involving the LAA or LA free wall.4
Aneurysm may mimic a mediastinal or cardiac tumor.
Although congenital in origin, most cases are
asymptomatic in childhood.5 In most of the patients, the
condition is diagnosed in the second to fourth decades of
IHJ-547-03.p65
380
Fig. 5. Left atrial angiogram by trans-septal puncture opacifying the left atrial
appendage (LAA) aneurysm. The delayed clearance and swirling motion of
contrast differentiate the LAA aneurysm from the cardiac chambers.
life on routine chest X-ray. It is likely that an aneurysm of
the LAA is initially small and asymptomatic, and becomes
obvious only after years of enlargement. Stasis in the
aneurysmal cavity accounts for thrombosis and systemic
embolization.1
LAA aneurysms can present with chest pain,
palpitations or systemic embolization. Nevertheless, most
cases are asymptomatic. Although our case had a massive
LAA aneurysm and autocontrast, he did not have any
embolic episodes.
11/19/2003, 11:26 PM
Indian Heart J 2003; 55: 379–381
Physical examination is often unrevealing.6 ECG may
reveal tachyarrhythmia, as in our case. A radiographic
differential for filling out of the cardiac bay region (Fig. 1)
includes partial absence of the pericardium along with
atrial herniation through the defect, paracardiac tumors
or cysts, enlarged coronary sinus, aneurysmal dilatation
of the LA due to mitral valvular disease, and pulmonary
artery aneurysm.
Echocardiography, radionuclide angiography, CT scan,
MRI, and cardiac catheterization have been used to
establish the diagnosis. Angiography requires trans-septal
puncture, and may not detect an LAA aneurysm filled with
a thrombus. In our case, the diagnosis was made during
screening echocardiography. Due to adequate
demonstration of the aneurysm and its origin by
transthoracic windows, transesophageal echocardiography
(TEE) was not required.
Foale et al. proposed the following criteria to diagnose
congenital LAA aneurysm:8
(i) origin from an otherwise normal LA; (ii) well-defined
communication with the LA; (iii) position within the
pericardium; and (iv) distortion of the LV free wall by the
aneurysm.
Our patient fulfilled all the 4 criteria for the diagnosis of an
LAA aneurysm.
Associated anomalies such as atrial septal defect (ASD),
persistent left superior vena cava, anomalous pulmonary
IHJ-547-03.p65
381
Chockalingam et al. Left Atrial Appendage Aneurysm 381
venous drainage, and renal artery anomalies have been
reported. 9,10 Aneurysmectomy abolishes recurrent
arrhythmias and thromboembolism. Thus, surgical
resection, with or without cardiopulmonary bypass, is
recommended even in asymptomatic patients.
References
1. Bramlet DA, Edwards JE. Congenital aneurysm of left atrial
appendage. Br Heart J 1981; 45: 97–100
2. Tanabe T, Ishizaka M, Ohta S, Sugie S. Intrapericardial aneurysm of
the left atrial appendage. Thorax 1980; 35: 151–153
3. Godwin TS, Avager P, Key JA. Intrapericardial aneurysmal dilatation
of left atrial appendage. Circulation 1988; 37: 397–400
4. Shaher RM, Alley R, Anis W, Mintzer J. Congenital enlargement of
the left atrium. J Thorac Cardiovasc Surg 1972; 63: 292–299
5. Behrendt DM, Aberdeen E. Congenital aneurysm of the left atrium.
Ann Thorac Surg 1972; 13: 54–59
6. Krueger SK, Ferlic RM, Mooring PK. Left atrial appendage aneurysm:
correlation of noninvasive with clinical and surgical findings: report
of a case. Circulation 1975; 52: 732–738
7. Comess KA, Labate DP, Winter JA, Hill AC, Miller DC. Congenital left
atrial appendage aneurysm with intact pericardium: diagnosis by
transesophageal echocardiography. Am Heart J 1990; 120: 992–996
8. Foale RA, Gibson TC, Guyer DE, Gillam L, King MF, Weyman AE.
Congenital aneurysms of the left atrium: recognition by crosssectional echocardiography. Circulation 1982; 66: 1065–1069
9. Parmley LF. Congenital atriomegaly. Circulation 1982; 25: 553–558
10. Labarre TR, Stamato NJ, Hwang MH, Jacobs WR, Stephanides L,
Scanlon PJ. Left atrial appendage aneurysm with associated
anomalous pulmonary venous drainage. Am Heart J 1987; 114:
1243–1245
11/19/2003, 11:26 PM
382 MukhopadhyayImages
et al. Noncompacted LV With Dysplastic Tricuspid Valve
Cardiovascular
Indian Heart J 2003; 55: 382–383
Noncompacted Left Ventricle in Association With
Dysplastic Tricuspid Valve
Saibal Mukhopadhyay, Jamal Yusuf, Umamahesh C Rangasetty, Vijay Trehan
Department of Cardiology, GB Pant Hospital, New Delhi
Fig. 1. Transthoracic four-chamber view showing prominent trabeculations with
deep recesses in the lateral wall (↑↑) of the left ventricle. The single arrow (↑)
shows the thick, incompletely coapting septal and anterior tricuspid leaflets,
and the enlarged right atrium.
Fig. 2. Short-axis view of the left ventricle at papillary muscle level showing
thick, spongy endocardium and thin, compact epicardium.
Fig. 4. Continuous-wave Doppler revealing a peak velocity of the tricuspid
regurgitant jet of 1 m/s.
Fig. 3. Color Doppler showing a laminar jet of severe tricuspid regurgitation
across the tricuspid valve.
A
20-year-old normotensive female admitted with rightsided hemiparesis of acute onset due to a cerebral
infarct was referred from the neurology ward for
echocardiography to rule out a cardiac source of embolism.
Two-dimensional (2-D) echocardiography revealed a
normal-shaped, nondilated left ventricle with prominent
Correspondence: Dr Jamal Yusuf, Department of Cardiology, GB Pant
Hospital, New Delhi 110002
IHJ-434-03.p65
382
trabeculations and deep intertrabecular recesses (Fig. 1,
double arrow). The trabeculations were localized
predominantly in the mid and apical segments of the left
ventricular lateral, anterior and inferior walls. The ratio of
the noncompacted to the compacted layer measured at endsystole was greater than 2:1 (Fig. 2). The affected segments
revealed hypokinesia, and the overall left ventricular
ejection fraction was 38%. On color Doppler echocardiography, the deep intertrabecular recesses were seen filling
with blood from the left ventricular cavity during diastole
11/19/2003, 11:24 PM
Indian Heart J 2003; 55: 382–383
Mukhopadhyay et al. Noncompacted LV With Dysplastic Tricuspid Valve 383
with reversed flow in systole. No thrombus could be
detected in the intertrabecular recesses. The mitral and
aortic valves were normal. The right atrium was enlarged
(Fig. 1) and the septal and anterior leaflets of the tricuspid
valve appeared thickened with incomplete coaptation in
systole (Fig. 1, single arrow). There was no excessive apical
displacement of the septal leaflet as seen in Ebstein’s
anomaly. Color Doppler echocardiography across the
tricuspid valve revealed a laminar jet of severe tricuspid
regurgitation (TR) (Fig. 3) with continuous-wave Doppler
revealing a peak velocity of the regurgitant jet of 1 m/s
(Fig. 4). Thus, a diagnosis of dysplastic tricuspid valve was
made. The right ventricle and pulmonary valve were
normal.
Noncompacted myocardium has been frequently
reported in patients with congenital left or right ventricular
outflow tract obstruction. In these patients with a “spongy
myocardium”, the recesses represent “persisting sinusoids”
that fail to regress during ontogenesis due to persistent
pressure overload, and communicate with the coronary
arteries.1–3 In contrast, isolated ventricular noncompaction
(IVNC) is considered a congenital anomaly due to the arrest
of compaction of the loose myocardial meshwork during
fetal ontogenesis, 4 when the intertrabecular recesses
covered with endothelial cells are filled with blood from the
ventricular cavity without evidence of communication to
the epicardial coronary artery system.2,5 These recesses
predispose to local thrombus formation but are often missed
on echocardiography when associated with prominent
trabeculations.6
Noncompacted myocardium and tricuspid valve
dysplasia as individual conditions are well described. Our
patient had all the characteristic echocardiographic
features of left ventricular noncompaction as described by
Jenni et al.4 along with a coexistent congenital anomaly—
tricuspid valve dysplasia—a combination not yet reported
IHJ-434-03.p65
383
in the literature, to the best of our knowledge. Early
diagnosis of ventricular noncompaction and the correct
management of such patients is crucial, as the clinical
morbidity includes heart failure, caused by progressive
ventricular dysfunction, arrhythmias and systemic embolic
events.7
Our patient presented with asymptomatic left
ventricular dysfunction detected incidentally on
echocardiography, but there was no clinical evidence of
right ventricular systolic dysfunction. The patient was put
on medical therapy with a combination of beta-blockers
and ACE inhibitors (to arrest negative remodeling and the
progression of heart failure), and oral anticoagulants to
prevent the formation of thrombi in the left ventricle.
References
1. Dusek A, Osadal B, Duskova M. Postnatal persistence of spongy
myocardium with embryonic blood supply. Arch Pathol 1975; 99:
312–317
2. Angelini A, Melacini P, Barbero F. Evolutionary persistence of spongy
myocardium in humans [Abstr]. Circulation 1999; 99: 247S
3. Lauer RM, Fink RM, Petry EL, Dunn MI, Deihl AM. Angiographic
demonstration of intramyocardial sinusoids in pulmonary valve
atresia with intact ventricular septum and hypoplastic right ventricle.
N Engl J Med 1964; 271: 68–72
4. Jenni R, Oechslin E, Schneider J, Jost CA, Kaufmann PA.
Echocardiographic and pathoanatomical characteristics of isolated
left ventricular non-compaction: a step towards classification as a
distinct cardiomyopathy. Heart 2001; 86: 666–671
5. Oechslin E, Jost CA, Rojas JR, Kaufmann PA, Jenni R. Long term follow
up of 34 adults with isolated left ventricular non-compaction: a
distinct cardiomyopathy. J Am Coll Cardiol 2000; 36: 493–500
6. Boyd MT, Seward JB, Tajik AJ, Edward WD. Frequency and location
of prominent left ventricular trabeculations at autopsy in 474
normal human hearts: implications for evaluation of mural thrombi
by two-dimensional echocardiography. J Am Coll Cardiol 1987; 9:
323–326
7. Ichida F, Hamamichi Y, Miyawaki T. Clinical features of isolated noncompaction of left ventricle. J Am Coll Cardiol 1999; 34: 233–240
11/19/2003, 11:24 PM
384
Letters
theEditor
Editor
Letters
to to
the
Seropositivity of Chlamydia
pneumoniae and Helicobacter pylori
Among Coronary Heart Disease
Patients and Normal Individuals in
a South Indian Population
T
he search for new risk factors that can satisfactorily
explain the prevalence and severity of coronary heart
disease (CHD) has brought into focus the role of infections,
particularly the association of Helicobacter pylori (H. pylori)
Chlamydia pneumoniae (C. pneumoniae), and cytomegalovirus with CHD.1 Although many such studies are available
from western countries, studies in the Indian context are
lacking. Identification of a causal linkage of any kind of
infection with CHD can lead to timely intervention with
antibiotics, which may decrease the disease burden.
One hundred and seventeen angiographically proven
patients (35–79 years of age) with unstable angina (UA),
and 16 patients with chronic stable angina (CSA) were
matched with 90 healthy blood donors (20–60 years of
age) free from clinical CHD confirmed by 12-lead resting
ECG. Fasting serum samples were drawn from these healthy
controls and patients. C. pneumoniae and H. pylori-specific
IgG was detected by the ELISA technique.
A total of 59 (58%), 9 (56%), and 48 subjects (53%)
were seropositive for H. pylori in the UA, CSA, and control
groups, respectively. The number of subjects seropositive
for C. pneumoniae in the UA, CSA, and control groups were
67 (66%), 15 (94%), and 73(81%), respectively. No
significant statistical difference in seropositivity was found
Letter-to-Editors.p65
384
Indian Heart J 2003; 55: 384–385
between the study group and the controls, either for H.
pylori or for C. pneumoniae. The prevalence of H. pylori
reported in our study is within the range reported in studies
from India (40%–74%).2 There has been no report on the
seropositivity of C. pneumoniae from India till date. Our study
showed a high prevalence of C. pneumoniae (70.1% in
patients, and 81% in controls), which is in agreement with
the normal Chinese population (61.5%).3
It has been postulated that in countries with poor
socioeconomic conditions, there may be a link between
CHD and some undefined environmental exposures,
including infections. It is possible that cardiovascular risk
increases with cumulative or earlier exposure to more
pathogens or specific potentially atherogenic microbes.4
References
1. Danesh J, Collins R, Peto R. Chronic infections and coronary heart
disease: is there a link? Lancet 1997; 350: 430–436
2. Kate V, Ananthakrishnan N, Ratnakar C, Badrinath S. Anti H. pylori
IgG seroprevalence rates in asymptomatic children and adults from
South India. Indian J Med Microbiol 2000; 19: 73–78
3. Ni AP, Lin GY, Yang L, He HY, Huang CW, Liu ZJ, et al. A seroepidemiologic study of Chlamydia pneumoniae, Chlamydia tranchomatis
and Chlamydia psittaci in different populations on the mainland of
China. Scand J Infect Dis 1996; 28: 553–557
4. Taylor C. Workshop on emerging issues in microbial infections and
cardiovascular diseases, October 1998. NIAID Council News 1999;
8: 5
Abhijit Chaudhury, D Rajasekhar, SAA Latheef,
G Subramanyam
Departments of Microbiology and Cardiology
Sri Venkateswara Institute of Medical Sciences, Tirupati
11/19/2003, 11:28 PM
Indian Heart J 2003; 55: 384–385
Delayed Tamponade Following the
Sudden Braking of a Speeding
Vehicle
M
otor vehicle accidents often cause blunt cardiac
trauma with pericardial hemorrhage and rapid
tamponade.1 We describe a patient who presented with
bleeding, not to the emergency services, but to the
cardiologist.
A 63-year-old hypertensive male on beta-blockers
presented with a 3-day history of dyspnea on exertion and
profound weakness. His symptoms started 1 day after the
sudden braking of his car while he was travelling in the
back seat without a seat belt. He reported having protected
himself by holding onto the seat in front of him, and denied
impact to the chest. He was well for a few hours but
developed pain in the back of the neck the same night. Over
the next 3 days, he developed progressive weakness and
dyspnea. On examination, his pulse rate was 80 bpm (on
atenolol) and the blood pressure 140/90 mmHg with a
pulsus paradoxus of 10 mmHg. The jugular venous
pressure was elevated to 15 mmHg and heart sounds were
faint. The ECG showed a relative decrease in the QRS
voltages compared to the previous recording. A chest Xray showed an enlarged cardiac silhouette with a
cardiothoracic ratio of 70%.
The patient's hemoglobin level was 12 g%; it had been
14.5 g% during a routine health checkup 3 months earlier.
Serum transminases and alkaline phosphatase were
elevated three-fold, as is common in subacute tamponade.
Letter-to-Editors.p65
385
Letters to the Editor 385
The troponin T concentration was normal (<0.01 ng/ml).
Echocardiography revealed a moderate-size pericardial
effusion with collapse of the right atrium, and exaggerated
respiratory variation in the tricuspid and mitral Doppler
flow velocities. The patient underwent a therapeutic
tapping of the pericardial fluid. Seven hundred and twenty
ml of bloody fluid was aspirated via the subxiphoid
approach and a pigtail catheter left inside for 24 hours.
There was no recurrence of effusion, and the patient made
an uneventful recovery. The fluid had a hemoglobin content
of 10 g%, was sterile on culture and had no malignant cells.
The patient was doing well on follow-up at 6 months.
We believe that the bleeding resulted from an injury
caused by the sudden deceleration of the car.2 Subacute
traumatic pericardial bleeds should be managed and
followed up like other cases of pericardial hemorrhage,
including long-term follow-up for the development of
constrictive pericarditis.2
References
1. Rashid MA, Wikstrom T, Ortenwall P. Cardiac injuries: a ten-year
experience. Eur J Surg 2000; 166: 18–21
2. Karmy-Jones R, Yen T, Cornejo C. Pericarditis after trauma resulting
in delayed cardiac tamponade. Ann Thorac Surg 2000; 74: 239–241
Rajiv Bajaj, Harbans Singh Wasir
Department of Cardiology
Batra Hospital
New Delhi
11/19/2003, 11:28 PM
386 Selected
Summaries
Selected
Summaries
Indian Heart J 2003; 55: 386–389
Comparison of Carvedilol and Metoprolol on Clinical Outcomes in
Patients With Heart Failure in the Carvedilol or Metoprolol
European Trial (COMET): Randomized Controlled Trial
PA Poole-Wilson et al. COMET Investigators. Lancet 2003; 362: 7–13
Summary
Comments
COMET was a multicenter, randomized, double-blind,
parallel-group trial comparing the effects of carvedilol and
metoprolol on the clinical outcome of patients with chronic
heart failure (CHF). The study involved 3029 patients from
341 centers in 15 European countries. Symptomatic NYHA
classes II–IV (<5% were class IV) CHF patients receiving
both angiotensin-converting enzyme inhibitors (ACE-I) and
diuretics for at least 2 weeks were included in the study. All
of them had left ventricular (LV) systolic dysfunction as
evidenced by ejection fraction (EF) <35% or left ventricular
end-diastolic dimension (LV-EDD) >6 cm, and fractional
shortening (FS) <20%. Patients with an unstable medical
condition, uncontrolled hypertension or recent change in
treatment were excluded from the study. Carvedilol (1511
patients) was started at 3.125 mg twice daily, and doubled
every 2 weeks to achieve a target dose of 25 mg twice daily.
Metoprolol was started at 5 mg twice daily, and stepped up
to 50 mg twice daily. The patients were followed up for a
mean duration of 58±6 months. The baseline
characteristics were similar in both the groups. The mean
age was 62±11 years, one-fifth were female, mean duration
of CHF was >40 months, and more than 50% had an
ischemic etiology. The mean EF was 26%±7%. About 60%
of patients were receiving digitalis but very few patients
were receiving angiotensin receptor blockers (ARBs). The
primary end-point of the study was all-cause mortality.
Later, a composite end-point of all-cause mortality or all,
cause admission was admitted as a second primary endpoint in recognition of its importance, after publication of
the findings of the MERIT-HF study. The all-cause mortality
was 17% lower with carvedilol (34% v. 40%; 95% Cl: 0.74–
0.93, p=0.0017). The survival advantage was apparent
within 6 months, and was consistent among all the
subgroups. The composite end-point was also 6% lower in
the carvedilol group, though this was statistically
nonsignificant (74% v. 76%; 95% CI: 0.86–1.02, p=0.122).
Sudden cardiac death was the most common mode of
death, accounting for 43% of deaths in the carvedilol group,
and 44% in the metoprolol group. Circulatory heart failure
contributed to one-third of deaths in both the groups.
Three-fourth of the patients in the carvedilol arm reached
the target dose (mean dose 41.8±14.6 mg), whereas 78%
achieved the target dose in the metoprolol group (mean
dose achieved 85±28.9 mg). However, the reduction in
heart rate was greater in the carvedilol group (13.3 beats/
min v. 11.7 beats/min; 95% CI: 2.7 to –0.6). The incidence
of side-effects and drug withdrawals (32%) were similar in
both the groups. The authors concluded that carvedilol
extends a survival advantage vis-a-vis metoprolol in
patients with symptomatic CHF.
In patients with symptomatic CHF, the aims of treatment
are two-fold. The first and foremost is to relieve symptoms
and second, even more important than the first, is to
improve survival. While diuretics and digoxin are well
known for the symptom relief they provide in CHF, they
confer very little, if any, survival advantage. In this context,
the only drugs that improve survival are ACE-I, betablockers, aldosterone antagonists, and ARBs. However, the
benefit achieved by a combination of these renin–
angiotensin–aldosterone system (RAAS) modifying drugs
is still controversial. For instance, the VAL-HEFT study
showed that while a combination of ACE-I with ARB, or
beta-blocker (BB) with ARB was beneficial, the combination
of all three agents (ACE-I + BB + ARB) is actually
detrimental. The second issue has been the actual drug
used. Among the beta-blockers, carvedilol (COPERNICUS,
CHRISTMAS, CAPRICORN), metoprolol (MDC, MERIT-HF),
and bisoprolol (CIBIS I and II) have all been shown to be
useful. However, which of these beta-blockers, if any, is
more beneficial is still uncertain. Theoretically, metoprolol
and bisoprolol are both β1- selective, and should therefore
be more effective. Carvedilol is not only β1- and β2-active,
but also blocks the α1-adrenergic receptors. However,
carvedilol has several other mechanisms by which it can
be useful in patients with CHF. It increases insulin
sensitivity, and has potent antioxidant action, thereby
improving endothelial dysfunction and reducing apoptosis.
Indeed, a recent meta-analysis has suggested that the use
of carvedilol led to a greater improvement in EF (one of the
prime mechanisms for improvement of survival) as
compared to metoprolol. The COMET trial is the first large
study to compare these two drugs head-on. This study
suggests that carvedilol is superior to metoprolol not only
in reducing the combined rate of mortality and hospital
admission but, more importantly, in improving survival (as
much as 17% over a 5-year period). However, this study is
not without limitations. The mean dose of metoprolol, i.e.
85 mg, is much lower than that achieved in the MERIT-HF
study (>162 mg). Secondly, the salt of metoprolol, i.e.
metoprolol tartarate, is also different from metoprolol
succinate (metoprolol CR/XL) used in the MERIT-HF study.
Some studies have shown that the tartarate salt may have
at least 30%–35% reduced bioavailability as compared to
the succinate salt. Indeed, the reduction in heart rate and
blood pressure was higher in the carvedilol arm, perhaps
reflecting inadequate dosage in the metoprolol arm.
Another important limitation of the study was that followup EF values were not obtained.
IHJ-Selected Summary.p65
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11/19/2003, 11:27 PM
Indian Heart J 2003; 55: 386–389
Selected Summaries 387
Efficacy of Perindopril in Reduction of Cardiovascular Events Among Patients With
Stable Coronary Artery Disease: Randomized, Double-Blind, Placebo-Controlled,
Multicenter Trial (the EUROPA Study)
KM Fox et al. The EUROPA Trial Investigators. Lancet 2003; 362: 782–788
Summary
EUROPA was a randomized, double-blind, placebocontrolled, largest-ever trial of the angiotensin-converting
enzyme inhibitor (ACE-I) perindopril, evaluating the
reduction of cardiac events in low-risk patients with proven
coronary artery disease (CAD) but with no evidence of CHF.
It enrolled 13 655 patients ≥18 years of age, and
documented CAD as evidenced by previous MI, coronary
revascularization, angiographically proven CAD (>70%
stenosis) or positive stress test in men. Patients with
evidence of CHF, hypotension/uncontrolled hypertension
or due for PCI, recent use of ACE-I or angiotensin receptor
blockers (ARBs), renal insufficiency or elevated serum
potassium (>5.5 mmol/L) were excluded from the study.
The primary end-point was combined CVS mortality +
nonfatal AMI + survival of sudden cardiac death (SCD).
Patients initially received 4 mg perindopril for 4 weeks,
increased to 8 mg for another 4 weeks. Patients were then
randomized to receive either 8 mg perindopril or a placebo
for at least 3 years, the dose being reduced to 4 mg if it was
not tolerated. The mean follow-up was 4.2 years. Overall,
baseline characteristics were similar in both the groups. The
mean age was 60±9 years, and 85% were male. They were
generally low-risk CAD patients, 92% on platelet inhibitors,
62% on beta-blockers, and 48% on statins. Perindopril
significantly reduced the combined end-point from 9.9%
in the placebo group to 8% (RR 20%, p=0.0003). The
beneficial effect became apparent at 1 year of treatment,
and was seen in all the sub-groups. Perindopril use was
associated with a reduction in all the secondary end-points
as well. Total mortality reduced by 11% (ns), MI decreased
by 23.9% (p=0.001), and CHF decreased by 39.2%
(p=0.002). About 50 patients needed to be treated with
perindopril over 4 years to prevent one major CVS event,
and this benefit was over and above the medications already
being used.
Comments
The HOPE study has already established the role of ACE-I,
especially ramipril, in patients with high-risk CAD. In the
EUROPA study, perindopril was chosen because of its
antiischemic and antiatherogenic effects, its Effects on
cardiovascular remodeling, and its blood pressure-lowering
effect. The baseline characteristics of the EUROPA study
were different from those of the HOPE study. In the HOPE
IHJ-Selected Summary.p65
387
study, all the patients were >55 years, whereas in the
EUROPA study, at least one-third of patients were <55
years. In addition, more HOPE patients had diabetes
mellitus, hypertension, stroke, and obstructive peripheral
vascular disease. This difference is well reflected in the
placebo event rates, where the total mortality in the HOPE
study versus the EUROPA study was 12.2% v. 7.4%; CVS
mortality 8.1% v. 4.4%, and Q wave MI 3.2% v. 2.1%. With
this background, the results of the EUROPA study were even
more remarkable and, indeed, may appear to extend the
indication of ACE-I to even low-risk CAD patients. However,
if we look carefully, even the CAD patients enrolled in the
two studies were different. In the HOPE trial, only about
one-third of the patients were post-MI, whereas in the
EUROPA trial, nearly two-thirds were post-MI. The role of
ACE-I in post-MI is already well established. If we consider
subgroup analysis, the benefit in the non-MI patients was
not statistically significant in the EUROPA study. In other
words, perindopril is effective in only those patients who
have suffered a prior MI. Thus, these results cannot be
directly extrapolated to the garden variety of CAD patients;
rather, they are more applicable to the post-MI population.
Furthermore, another important limitation of the EUROPA
study is that the ejection fraction was not considered. Since
most patients in the EUROPA study were post-MI, it is likely
that the mean ejection fraction in this study would be low.
The role of ACE-I in patients with a low ejection fraction is
again well established. It can be argued that the effect of
perindopril could be due to its antihypertensive effect.
However, the BP reduction was small, 5/2 mmHg, which
could not account for the large reduction in CVS events. To
better understand the mechanism of CVS event reduction,
5 substudies of EUROPA are under way. The PERTINENT
study is evaluating the predictive value of several plasma
and serum markers associated with atherosclerosis, and the
effect of perindopril on these levels. The PERFECT study
will measure blood flow in the brachial artery using B-mode
imaging. The PERSPECTIVE study aims to investigate the
effects of perindopril on progression and regression in
diabetics, and the PERGENE study will genetically
characterize the EUROPA population. The results of these
studies are expected within a year. Another interesting
point that has emerged from the EUROPA study is that
mortality reduction was superior in the subgroup of
patients on beta-blockers. The reduction of events in
patients not on beta-blockers was statistically insignificant.
Further studies will be required to clarify this concept.
11/19/2003, 11:27 PM
Indian Heart J 2003; 55: 386–389
388 Selected Summaries
Beneficial Effect of Immediate Stenting After Thrombolysis
in Acute Myocardial Infarction
B Scheller et al. SIAM III study group. J Am Coll Cardiol 2003; 42: 634–641
Summary
The Southwest German Interventional Study in Acute Myocardial
Infarction (SIAM III) study is a multicenter, randomized,
prospective, controlled trial in which immediate stenting after full
thrombolysis was compared with the conservative approach of
delayed stenting after 2 weeks in patients presenting with acute
STEMI. The study included patients presenting within 12 hours
of the onset of symptoms with diagnostic electrocardiograms who
had no contraindication to thrombolysis. Angiographic inclusion
criteria were an infarct-related coronary artery >2.5 mm,
diameter stenosis of at least 70% or TIMI flow <grade 3. Patients
were recruited from community hospitals located within 34 km
of an interventional center. Reteplase was administered in 2
boluses of 10 IU 30 min apart. Patients also received 250 mg
aspirin IV, and a bolus of 5000 IU heparin, followed by an infusion
adjusted to maintain an activated partial thromboplastin time of
50 to 70 ms. During thrombolysis, the patients were randomized
to either immediate or elective stenting. Patients randomized to
immediate stenting were shifted to interventional centers within
6 hours where the infarct-related artery was stented; 2 weeks later,
a repeat angiography was performed. The second group
underwent elective angiography and stenting performed at 2
weeks. Patients in both the groups were clinically followed up at
regular intervals, and repeat angiography was scheduled at 6
months. A total of 163 patients were included in the study. Group
I (immediate stenting group) had a significant reduction in the
combined end-point of ischemic events, death, reinfarction, and
target lesion revascularization at 6 months (25.6% v. 50.6%,
p=0.001). This beneficial effect was largely driven by a reduction
in recurrent ischemic events (4.9% v. 28.4%, p=0.01). On an
intention-to-treat basis, immediate stenting was also associated
with a reduction in the 6-month combined end-point of death,
reinfarction, and target vessel revascularization (27.7% v. 39.8%,
p=0.049). Patients with stenting showed an improvement in LV
function at 2 weeks with further improvement at 6 months,
whereas the delayed stenting group (group II) showed no
statistically significant improvement in LV function. Major
bleeding complications occurred in 9.8% of patients who
underwent immediate stenting versus 7.4% in the delayed stenting
group (p=0.374). There were 5 deaths in group II within 48 hours
of thrombolysis, whereas all the patients in group I survived the
acute phase. Immediate stenting after thrombolysis is significantly
more beneficial compared to delayed stenting.
Comments
Thrombolysis results in TIMI-3 flow in only 60% of patients with
acute MI. Moreover, around a third of those thrombolyzed have
recurrent ischemia. Numerous studies have shown that primary
PCI is superior to pharmacologic thrombolysis with higher
reperfusion rates, and improved event-free survival. The main
drawback remains the immediate availability of centers with the
facility for PCI. Hence, in a real-world situation, a considerable
time delay is usually encountered in transportation of the patient,
and mobilization of appropriate resources. As we are aware, time
IHJ-Selected Summary.p65
388
is all-important in salvage of the myocardium. The ACC/AHA
recommends a door-to-balloon time of 90±30 min, but in a dayto-day situation, this is usually not possible. In the National
Registry of Myocardial Infarction (NRMI), there was a median
treatment time delay of >2 hours in almost 90% of patients. In
the recently published results of the DANAMI-2 study, there was
a lower composite end-point of death, MI or stroke at 30 days in
patients who were transferred from community hospitals to
tertiary care centers with intervention facilities, compared with
patients receiving on-site thrombolysis (8.5% v. 14.2%, p=0.002).
A similar benefit has been seen in the PRAGUE study, as well as
the AIR-PAMI study. Though these trials have shown that the time
delay in PCI is offset by the superiority of the results of angioplasty
over thrombolysis, the door-to-balloon time remains important.
In the NRMI registry, a door-to-balloon time >2 hours was
associated with an increase in mortality. Numerous fibrinolysis
trials have shown that the time from the onset of symptoms to
vessel recanalization is a predictor of myocardial salvage and
survival. Given the lack of widespread availability of PCI centers,
alternative approaches with a combination of pharmacologic and
mechanical revascularization methods are being tried. The
rationale behind facilitated PCI was to improve outcomes by
attempting to achieve earlier reperfusion while awaiting definitive
intervention at a center with PCI facility. This combination
approach is an attempt to buy time, and widen the therapeutic
window for revascularization. Moreover, patients have a better
TIMI flow grade and lesser thrombus burden, thus reducing the
chances of microvascular embolization, improving lesion focus,
and improving the overall results. However, earlier attempts with
this complementary therapy were not encouraging. Data from the
Thrombolysis and Angioplasty in Myocardial Infarction (TAMI1) study, and the European Cooperative study group showed no
benefit in survival or ventricular function, and were in fact
associated with a higher complication rate. However, the
development of bolus thrombolytics with enhanced fibrin
sensitivity, and excellent safety and efficacy profiles, along with
improvement in PCI hardware, including thrombectomy and
distal protection devices, have led to a resurgence in the use of
facilitated PCI.
In this trial, the time to angiography was 6.7 hours, exceeding
the currently recommended time. But the setting was a real-world
situation that would be commonly encountered in practice. In the
SIAM III study, over 60% of patients in the immediate stenting
group had TIMI-3 flow; this figure increased to 98%. This
translated into an improved LV function at 2 weeks and 6 months.
Despite the long time taken till intervention, there was a clear
benefit, and no increase in the complication rates. In conclusion,
this trial has proved the relative superiority of thrombolysis
followed by immediate stenting, despite the time involved in
transfer to the tertiary care center. The use of Gp IIb/IIIa
antagonists would further improve the outcome of immediate
stenting. In conclusion, immediate stenting after thrombolysis is
safe, and improves event-free survival as well as ventricular
function compared with elective stenting at 2 weeks following MI.
11/19/2003, 11:27 PM
Indian Heart J 2003; 55: 386–389
Selected Summaries 389
Sirolimus-Eluting Stents Versus Standard Stents in Patients
With Stenosis in a Native Coronary Artery
Moses et al. SIRIUS Investigators. N Engl J Med 2003; 349: 1315–1323
Summary
Comments
The SIRIUS investigators conducted a randomized doubleblind trial in 1058 patients with a newly diagnosed single
lesion in a native coronary artery, comparing a sirolimuseluting stent with a standard stent. Although previous trials
have shown a reduction in restenosis rates with sirolimus
stents, the patients enrolled were at a lower risk for
restenosis with discrete lesions. This study enrolled patients
with more challenging coronary lesions with the majority
(56%) having class B 2 or C lesions (ACC/AHA classification). The average vessel diameter was 2.8 mm, and the
mean lesion length was 14.4 mm. There were 533 patients
in the sirolimus stent group, and 525 in the standard stent
group. The groups were well matched with respect to
demographical characteristics, cardiac risk profile,
symptomatology, lesion anatomy, and procedural factor.
Follow-up angiography (performed in around 85% of
patients in both groups) showed that the minimal luminal
diameter stenosis, and the late lumen loss in the in-stent
zone as well as the in-segment zone were significantly
(p=0.001) better in the sirolimus stent group.
There was a higher rate of in-stent restenosis and insegment stenosis (35.4% and 36.3%, respectively) in the
standard stent group compared with the medicated stent
group (3.2% and 8.9%, respectively). Intravascular
ultrasound revealed a reduced neointimal volume in the
in-stent zone (4.4 mm 3 v. 57.6 mm 3, p<0.001). The
primary end-point of target vessel failure rate (composite
of death from cardiac causes, myocardial infarction, and
repeat revascularization) within 270 days was reduced by
58% with sirolimus stents (110 patients v. 56 patients,
p<0.001). This reduction was driven largely by a decrease
in the frequency of the need for revascularization of the
target vessel (16.6% v. 4.1%, p<0.001)). Diabetes was
significantly associated with an increased risk of restenosis
along with reference vessel diameter and lesion length.
However, sirolimus stents showed a consistent benefit even
in these high-risk subgroups as compared with standard
stents.
Sirolimus (rapamycin) is a macrolide antifungal with
powerful immunosuppressant properties; it inhibits several
regulators of cell-cycle progression, and the migration of
vascular smooth muscle cells. This unique property led to
its use in coronary artery stents to prevent neointimal
proliferation. The Randomized Study with the Sirolimus
Eluting Bx Velocity Balloon Expandable Stent (RAVEL)
showed a significant reduction in the frequency of in-stent
restenosis (from 26.6% to 0%). The present study enrolled
patients with a higher frequency of cardiac risk factors,
such as diabetes and hypercholesterolemia, more complex
morphology, and longer lesions. In the RAVEL study, there
were no type C lesions, and the mean lesion length was
9.58±3.25 mm compared with 14.4±5.8 mm in the
present study. Similarly, only 19% of the patients had
diabetes and 40% dyslipidemia compared with 26% and
74% in this study, respectively. Intravascular ultrasound
revealed a 92% reduction in neointimal volume, a 77%
reduction in the rate of target lesion revascularization, and
an 85% reduction in the rate of non-QMI. The high
frequency of in-segment restenosis compared to in-stent
restenosis (8.9% v. 3.2%) in the sirolimus stent group was
due to a higher rate of restenosis at the proximal margin
of the stent, and is attributed to balloon injury to the vessel
prior to stent deployment. The authors recommend the use
of shorter balloons and longer stents that would have no
exposed balloon-injured area. The restenotic lesions were
focal compared with diffuse disease with standard stents,
and hence more amenable to complex balloon angioplasty.
The encouraging results from the trial suggest that special
stents may maintain their superiority over standard stents
in a diverse patient population. As sirolimus-coated stents
move into general use, and with a longer follow-up, it is
likely that the rate of restenosis will be higher. This trial
has shown the beneficial effect of sirolimus-coated stents
in a population at a higher risk, and with more complex
disease than previous studies.
IHJ-Selected Summary.p65
389
11/19/2003, 11:27 PM
Calendar of Conferences
Indian Heart J 2003; 55: 390
November 14–15, 2003, 4th Annual Conference of
Nuclear Cardiological Society of India, Vellore, India
Contact: Organizing Secretary
Department of Nuclear Medicine
Christian Medical College
Vellore, Tamil Nadu, India
Fax: 0416 2232103
e-mail: [email protected]
November 7–10, 2004, 77th Scientific Session,
American Heart Association (AHA), New Orleans,
Louisiana, USA
Contact: American Heart Association
7320 Greenville Avenue
Dallas TX 75231, USA
Tel: 1 214 373 6300
Fax: 1 214 373 3406
December 4–7, 2003, 55th Annual Conference of
Cardiological Society of India, Kolkata, India
Contact: Dr Asok Kumar Kar, Organizing Secretary
Indian Heart House
P-60, CIT Road, Scheme VIIM,
Kankurgachi, Kolkata 700054, India
Fax: 033 355 6308
e-mail: [email protected]
November 26–28, 2004, 3rd International Congress
on Cardiovascular Disease, Taipei, Taiwan
Contact: Dr CE Chiang
Taiwan Society of Cardiology
7F, No. 27, Min-Chuan, West Road
Taipei 104, Taiwan
Fax: 886 2 25076180
e-mail: [email protected]; [email protected]
January 9–11, 2004, Joint Meeting of International
Society for Heart Research and International
Academy of Cardiovascular Sciences, Lucknow, India
Contact: Professor VK Puri, Organizing Secretary
Department of Cardiology
CSM Medical University
Lucknow, India
Fax: 0522 225 5830
e-mail: [email protected]
November 28–30, 2004, 10th World Congress on
Clinical Nutrition, Thailand
Contact: Dr Buncha Ooraikul
or Dr Tapan Basu, Department of Food Science
and Nutrition, University of Alberta, Edmonton
Canada T6G 2M
Fax: 403 4924821
e-mail: [email protected]
May 6–9, 2004, 4th Congress of the Asian Pacific
Society of Atherosclerosis and Vascular Disease, Bali,
Indonesia
Contact: Dr Slamet Suyono, MD
Pacto Convex Ltd, Lagoon Tower Level B-1
Jagarta Hilton International
JI Gatot Subroto, Jakarta 10270, Indonesia
Fax: 62 21 5705798
e-mail: [email protected]
Cal of Conference.p65
390
May 21–25 2005, 4th International Conference on
Preventive Cardiology, Foz do Iguassu, Brazil
Contact: Dr Mario Maranhao, Chairman, Congress
Internationales SA/Lidy Groot Congress Events
P.O. Box 83005 1080, AA Amsterdam
The Netherlands
Fax: 3120 6758236
e-mail: [email protected]
11/19/2003, 11:22 PM