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Indian Heart J 2004; 56: 613–617
Singh et al. Coronary Slow Flow Phenomenon
613
Editorial
Coronary Slow Flow Phenomenon:
An Angiographic Curiosity
Sandeep Singh, SS Kothari, VK Bahl
Department of Cardiology, All India Institute of Medical Sciences, New Delhi
C
ardiologists are familiar with the phenomenon of slow
progression of angiographic contrast in the coronary
arteries in the absence of stenosis in the epicardial vessels
in some patients presenting with chest pain. The coronary
slow flow phenomenon (CSFP), first described in 1972,
remains scantily studied.1-3 This phenomenon should be
distinguished from occurrence of slow flow in the context
of coronary reperfusion therapy such as angioplasty or
thrombolysis that is associated with different pathophysiological and clinical implications. Similarly, coronary
slow flow associated with coronary artery spasm, coronary
artery ectasia (CAE), myocardial dysfunction, valvular
heart disease and certain connective tissue disorders
involving coronary microvasculature is easy to
understand. 3,4 CSFP may occassionly also result from
inadvertent air-embolism during angiography or may be
due to an overlooked ostial lesion. However, it is not certain
whether CSFP in the absence of any of these known causes
represents merely an angiographic curiosity or has special
physiologic or therapeutic implications. In this editorial we
focus on the current knowledge regarding CSFP
manifesting in the absence of any known etiology.
Incidence and Methods of Assessment
Overall, CSFP is observed in approximately one percent of
the patients undergoing coronary angiography, specially
in patients presenting with acute coronary syndrome
(usually unstable angina). In the Thrombolysis In
Myocardial Infarction (TIMI)-IIIA study, 4% of patients
presenting as unstable angina but with normal/
insignificant epicardial coronary artery disease (CAD)
showed impaired angiographic filling suggestive of CSFP.5
Mangieri et al. 6 reported an incidence of 7% of this
phenomenon in patients suspected to have CAD, however
the documentation of slow flow was visual without any
objective criteria. Usually TIMI flow grade scheme is
Correspondence: Dr VK Bahl, Professor of Cardiology, All India Institute
of Medical Sciences, New Delhi 110029. e-mail: [email protected]
EDITORIAL.p65
613
followed to assess coronary blood flow. It reflects the speed
and completeness of the passage of the injected contrast
through the coronary artery.7,8 This method is a qualitative
way of assessing coronary flow and is limited by significant
inter-observer variability. In contrast, corrected TIMI frame
count (CTFC) is a more quantitative and reproducible index
of coronary artery flow.9 It represents the number of cine
frames required for contrast to reach the standardized distal
coronary artery landmarks. CSFP is defined as CTFC greater
than 2 standard deviations (SD) from normal published
range for that particular vessel.9,10 In a retrospective study
using these objective criteria of CTFC, as high as 25% of
patients evaluated for typical angina or angina-like chest
pain syndrome with normal epicardial coronary arteries
showed this phenomenon.10
Clinical Profile
CSFP is more often seen in males who are current
smokers.3,11 This is in contrast to “Syndrome X” which is
predominantly a disorder of post-menopausal females.11
Patients with CSFP more often present with rest pains,
requiring urgent hospital admission. Both resting
electrocardiographic (ECG) abnormalities as well as positive
exercise stress testing are more frequent in patients with
CSFP as compared with patients having normal coronary
flow.3 Myocardial perfusion scintigraphy shows reversible
perfusion abnormalities in 30-75% of such patients.12,13 On
long-term follow-up the clinical course is usually benign
in patients with CSFP, although it is frequently punctuated
with remitting, relapsing anginal episodes resulting in
considerable impairment in quality of life.14 Over 80% of
these patients experience recurrent chest pain and onethird of them require readmission for an acute
exacerbation.3,15 Occasionally, patients may present with
evidence of acute myocardial infarction.3,16 Recently, Atak
et al. 17 have reported abnormalities of corrected QT
dispersion in patients with CSFP. Whether this predisposes
to ventricular arrhythmias and sudden cardiac death in
these patients is not clear.
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Indian Heart J 2004; 56: 613–617
614 Singh et al. Coronary Slow Flow Phenomenon
Pathophysiology
The pathophysiological mechanisms of CSFP remain
uncertain. The coronary circulation is traditionally
considered as a two-tier model. The first tier consists of
epicardial vessels, which are also referred to as “conductance vessels” as these do not pose any resistance to
blood flow. The second compartment consists of “small
vessels” of <400 µm (“resistive vessels”) which primarily
regulate myocardial blood flow in the absence of any
significant obstructive epicardial stenosis.18
Is it a disease of small vessels?: “Small vessel dysfunction” has been typically implicated in the pathogenesis of
CSFP since its first description.2 The evidence of affliction
of small vessels comes from the results of histopathological
examination of ventricular biopsy specimens in patients
with CSFP.6,19 Mosseri et al.19 reported abnormalities of
small coronary arteries along with myocardial hypertrophy
and patchy fibrosis in the biopsy samples from right
ventricle of six patients with CSFP. However, majority of
these patients had concomitant diseases that could have
induced these changes. Later, Mangieri et al.6 reported
histopathological examination of left ventricular
endomyocardial biopsy specimens in a more homogenous
group of 10 patients of CSFP who did not have any other
cardiac or systemic diseases. There was evidence of small
vessel affliction i.e. endothelial thickening due to cell edema,
capillary damage and reduced luminal diameter of the
small vessels. Electron microscopy revealed irregular
nuclear morphology and several indentations of the
nucleolemma and pycnosis. But it is not certain whether
slow flow leads to these histopathological changes or
whether these changes cause slow flow, though the later
appears more likely.12 Also, these fixed structural changes
cannot explain the acute presentation in the majority of
these patients. The clinical and angiographic variability
implies a significant dynamic component to the coronary
microvascular resistance. It is noteworthy that only a third
of the patients with CSFP fulfilled the criteria on a repeat
angiographic study.15 Thus CSFP lacks reproducibility. It is
postulated that this dynamic increase in microvascular tone
is due to “microvascular spasm” resulting in recurrence of
symptoms. Exact mechanism for this dynamic response is
not well elucidated. It is plausible that intermittent release
of certain autacoids (neuropeptide-Y, endothelin-1, thromboxane-A2 etc.) mediate coronary vasoconstriction.15,20-22
Even invasive hemodynamic and metabolic parameters
do not consistently suggest a uniform mechanism for CSFP.
Resting hemodynamic parameters of heart rate, blood
EDITORIAL.p65
614
pressure or the double product fail to explain the occurrence
of CSFP.13,15 The vasodilatory response of the microvasculature to provocative stimuli is less clear and has evoked
mixed responses.15,23 Lower resting coronary sinus (CS)
oxygen saturation has been observed in patients with CSFP
as compared to controls for a similar myocardial oxygen
demand.15 This implies a higher transcoronary myocardial
extraction caused by the delayed resting coronary perfusion
consistent with CSFP. Whether this delayed perfusion
results in myocardial ischemia either during rest or during
stress needs to be addressed. Yaymaci et al.24 investigated
the presence of stress-induced myocardial ischemia in
patients with CSFP by measuring two metabolic indicators
of ischemia i.e. coronary arteriovenous oxygen content
difference and lactate production. Although majority of
patients developed anginal pain with atrial pacing, only few
(17%) revealed evidence of metabolic ischemia. Thus,
angina pectoris in most patients with CSFP does not
originate from myocardial ischemia as demonstrated by
metabolic parameters. However, of the subset of patients
who showed evidence of metabolic ischemia, majority
showed a perfusion defect using single photon emission
computed tomography (SPECT) that anatomically
correlated well with the vessel showing CSFP. These
differences in patients with CSFP may be explained by the
variability in the degree of coronary flow reserve (CFR),
which, per say, is an indicator of microvascular function.
Recently, Sezgin et al.25 reported evidence of endothelial
dysfunction in patients with CSFP using simple method of
measuring flow-mediated vasodilation (FMD) of the
brachial artery. It has been suggested that FMD is
predominantly due to endothelial release of nitric oxide
(NO). There was a strong and inverse relationship between
CTFC and percentage of FMD in patients with CSFP thereby
suggesting that endothelial NO activity is impaired in these
patients.25
Can we exclude epicardial coronary artery disease?
It is well appreciated that diffuse atherosclerosis may be
present in angiographically normal appearing vessel.
Further, macro- and microvascular disease may also
coexist.26,27 A recent study investigated the significance of
epicardial vessel affliction by studying coronary anatomy
using intravascular ultrasound (IVUS) and measuring
epicardial resistance using fractional flow reserve (FFR) in
patients with CSFP.27 FFR is an index of resistance to flow
along the epicardial vessel and is defined as the ratio of distal
to proximal coronary pressures.18 In maximal hyperemia
(e.g. adenosine-induced), FFR is independent from
microvascular bed. If there is no resistance along the artery
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Indian Heart J 2004; 56: 613–617
Singh et al. Coronary Slow Flow Phenomenon 615
as expected in normal epicardial artery, there is no pressure
decline and FFR approaches unity. Surprisingly, a decline
in the distal coronary pressure leading to significantly lower
FFR value was seen in the patients exhibiting slow flow
phenomenon. There was a strong negative correlation
between CTFC and FFR. Interestingly, the patients showing
perfusion defects using myocardial perfusion scintigraphy
had significantly lower FFR values, signifying even higher
epicardial resistance. There was diffuse intimal thickening
and calcification throughout the epicardial arteries on
IVUS. A negative correlation was observed between intimal
thickness and FFR. It is postulated that decreased FFR levels
are due to increased resistance in the epicardial coronary
arteries resulting from diffuse atherosclerotic disease as
demonstrated by IVUS.27
Thus, at present, the data are not sufficient to delineate
the borders of this phenomenon. Whether it is due to involvement of predominantly macro- or microvasculature
of the heart is not certain. It is hypothesized that CSFP may
be a form of early phase of atherosclerosis in some patients.
However, certain other factors may also contribute to CSFP.
1 (ET-1) and NO are important molecules that modulate
vasodilatory response to stress (rapid atrial pacing/
exercise). Recently published studies have highlighted the
imbalance between ET-1 and NO release in patients with
CSFP as compared to controls with normal coronary
flow.32,33 No significant difference in arterial and coronary
sinus NO plasma levels was seen in the two groups, at
baseline as well as after pacing. In contrast, basal plasma
ET-1 levels were higher in patients with CSFP. Rapid atrial
pacing resulted in significantly higher coronary sinus levels
of ET-1 in patients with CSFP, which also correlated well
with the CTFC. Furthermore, in patients with CSFP,
coronary sinus ET-1 levels also increased significantly as
compared to femoral artery ET levels. Even correlation of
ET-1 levels and intimal thickness of coronary artery using
IVUS has been reported.32 It is possible that CSFP results
from imbalance of ET-1, a potent vasoconstrictor leading
to deregulation of vascular tone even in the very early
stages of plaque formation. More studies are required to
unravel the molecular mechanisms of CSFP.
Miscellaneous factors: It appears that CSFP may
represent a heterogeneous group of disorders unified
because of characteristic angiographic appearance. Slow
flow has been characteristically seen in ectatic and
aneurysmally dilated coronary arteries (dilated coronaropathy) with proportionately more impairment of blood
flow in these vessels with increasing coronary artery
diameters. 28 This is in accordance with the HagenPoiseuille’s equation which states that resistance to flow
within a tube depends on the dimensions of the tube and
the viscosity of the fluid in it.29 However, the relationship
of CSFP in relation to vessel diameter has not been well
studied. Furthermore, importance of other rheological
factors, blood viscosity, fibrinogen levels and hyperlipidemia
(contributing to increased blood viscosity) in these patients
has not been studied. Hematocrit and fibrinogen are the
major determinants of blood viscosity. Increased blood
viscosity leading to decrease in coronary blood flow reserve
has been associated with hyperlipidemia and high
fibrinogen levels.29,30 The therapeutic implications, if any,
of these findings remain to be studied. Similarly,
contribution of CSFP in patients with syndrome X has not
been sharply delineated and these may represent
overlapping phenomena. 10 Other rare causes may be
important in appropriate settings. For example, slow
coronary filling has been reported in patients with cocaine
use even in the absence of coronary artery spasm.31
Treatment
Proposed mechanisms at molecular level: Endothelin-
EDITORIAL.p65
615
There are no definite treatment modalities for patients with
CSFP. Conventional antianginal therapy is of limited value
in the chronic management in these patients.34 Nitrates are
ineffective as their biotransformation to active metabolite
is diminished due to deficiency of required enzymes in
coronary microvessels as compared to larger epicardial
coronary arteries.35,36 In contrast, dipyridamole may be
effective due to its predominant action on the small vessels
of diameter less than 200 µm. It blocks uptake of adenosine
by both vascular endothelium and erythrocytes and
prevents its conversion to inactive metabolites. This results
in re-distribution of vascular resistances due to vasodilation
of the small vessels.36,37 Mangieri et al.6 demonstrated the
effectiveness of dipyridamole in acute setting during
coronary angiography in patients with CSFP. Intracoronary
administration of this drug relieved microvascular tone and
accelerated contrast run-off in coronary arteries without
changing the diameter of epicardial coronary vessels. As
expected, intracoronary nitroglycerine failed to produce
any beneficial effect in these patients. Demirkol et al.12 also
observed improvement in myocardial perfusion with
dipyridamole infusion using myocardial perfusion SPECT.
Long-term oral therapy with dipyridamole was assessed by
Kurtoglu and associates 38 in an open-label fashion.
Coronary flow returned to normal levels in majority of
the vessels as adjudged by using CTFC. This was
accompanied with complete relief from chest pain in two-
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Indian Heart J 2004; 56: 613–617
616 Singh et al. Coronary Slow Flow Phenomenon
third of patients and decrease in symptoms in the
remaining. Since this phenomenon, per say, is punctuated
by remissions in clinical course, more data using casecontrol studies are required to confirm the above
observations.
Conventional calcium L-channel blockers (diltiazem/
verapamil) are of limited value in alleviating symptoms.
This is perhaps due to absence of voltage-gated L-type
calcium channels in microvessels, as shown by studies in
the animal models.39 Instead, the microvascular tone may
appear to rely on other types of voltage-gated calcium
channels, possibly of the T-type.40 Mibefradil is a long-acting
calcium T-channel antagonist that was approved by FDA
in 1997 for the treatment of hypertension and chronic
stable angina pectoris. Unfortunately the drug was
voluntarily withdrawn shortly after its launch due to its
numerous clinically relevant drug interactions.41 Recently,
Beltrame et al.34 assessed the acute and long-term clinical
benefits of mibefradil in patients with CSFP by exploring
its beneficial effects on microvessels. There was significant
acute angiographic improvement in coronary flow indices
with this drug. CSFP was abolished in approximately threefourth of the vessels at 30 min after the drug intake. This
occurred without any significant changes in the epicardial
vessel diameter or rate-pressure product. Interestingly, the
improvement in flow indices occurred primarily in vessels
with CSFP as compared to vessels with normal epicardial
flow. In accordance with these acute angiographic results,
long-term clinical benefits with this drug were also
observed. In a randomized, double blind, placebocontrolled, cross-over study, there was substantial reduction in frequency of angina by 56% (p<0.001), episodes of
prolonged angina by 74% (p<0.001), and sublingual
nitrate consumption by 59% (p<0.01) along with
improvement in physical quality of life (p=0.003).34 Since
the drug has been formally withdrawn, these observations
may stimulate further research with similar molecules.
Recently, a three-dimensional pharmacophore model
consisting of three hydrophobic regions, one hydrogen
bond acceptor and one positive ionizable region has been
hypothesized for T-type calcium channel blockers. 42
Whether it acts as a valuable tool in designing new ligands
for this group of drugs remains to be seen.
Thus, CSFP continues to intrigue the clinicians. It
appears to represent a heterogeneous group of disorders.
In some it may represent an early stage of atherosclerosis
with endothelial dysfunction and in others it may indicate
microvascular dysfunction or other unknown disorders.
The prognosis appears good although symptoms tend to
recur. Further advances in the understanding of
EDITORIAL.p65
616
pathophysiologic mechanisms and treatment of CSFP are
awaited.
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618 Kypson
et al.
Review
Article
Indian Heart J 2004; 56: 618–621
Robotically Assisted Cardiac Surgery
Robotically Assisted Cardiac Surgery
Alan P Kypson, W Randolph Chitwood Jr
Division of Cardiothoracic and Vascular Surgery, The Brody School of Medicine, East Carolina University
North Carolina, USA
M
itral valve operations have typically been performed
through a median sternotomy, which provides
generous exposure and allows ample access to all cardiac
structures. Over the past 10 years, improvements in
endoscopic techniques have resulted in a dramatic increase
in non-cardiac minimally invasive surgical procedures.
Surgeons and patients have been enthused by the benefits
and possibilities of minimally invasive heart valve surgery.
Initially, standard endoscopic instruments were used but
they proved to be ineffective. As a result, computerenhanced instrumentation systems were developed.
Advances in closed-chest cardiopulmonary bypass and
myocardial protection as well as improved intracardiac
visualization have hastened the shift toward efficient and
safe minimally endoscopic cardiac surgery. Today, mitral
valve surgery can be done through small incisions using
either robotic or endoscopic assistance and has become
standard practice for an increasing number of cardiac
surgeons.
Evolution of Robotic Mitral Valve Surgery
Minimally invasive robotic-assisted cardiac surgery has
evolved through graded levels of difficulty with increasingly
less exposure. In mitral valve surgery, the progression to
complete dependence on three-dimensional (3D)-assisted
vision and telemanipulation has been a conscious step-wise
evolution. Consequently, complex reconstructive mitral
valve operations can be performed completely using a
robotic interface. Thus far, surgical results have been
encouraging and have hastened adoption of these less
invasive methods.
Innovations in computer-assisted telemanipulation
cardiovascular surgery occurred rapidly in the late 1990s.
By 1998, Carpentier et al. 1 performed the first truly
endoscopic mitral valve repair using an early prototype of
the da Vinci™ (Intuitive Surgical, Sunnyvale, CA) surgical
system. In May 2000, our group performed the first
Correspondence: Dr Alan P Kypson, Assistant Professor of Surgery
Division of Cardiothoracic Surgery, The Brody School of Medicine, Room 252
600 Moye Boulevard, Greenville, NC 27858, USA
e-mail: [email protected]
IHJ-763-04 review article.p65
618
complete mitral valve repair in North America using the
da Vinci™ system.2 In that operation a large P2 trapezoidal
resection was done with the defect closed using multiple
interrupted sutures followed by implantation of an
annuloplasty band. Lange and associates in Munich were
the first to perform a totally endoscopic mitral valve repair
using only 1 cm ports and da Vinci™.3 Although we still
use a 4 cm incision for assistant access, robotic technology
has progressed to a point where totally endoscopic mitral
valve surgery has become the operation of choice for
patients having isolated mitral valve pathology.
Patient Selection
All patients with isolated degenerative mitral valve disease
are now considered for a robotic mitral valve repair. In the
development of a robotic mitral valve repair program, strict
inclusion and exclusion criteria should be followed (Table
1). Patients with severely calcified mitral annuli are not
suitable candidates. De-calcification methods will require
further instrument development. However, moderate
annular calcification alone does not preclude patients from
undergoing a minimally invasive approach.
Table 1. Robotic mitral surgery: exclusion criteria
Previous right thoracotomy
Renal failure
Liver dysfunction
Bleeding disorders
Severe pulmonary hypertension
Significant aortic or tricuspid valve disease
Coronary artery disease requiring surgery
Recent myocardial ischemia (<30 days)
Recent stroke (<30 days)
Severely calcified mitral valve annulus
Patients with poor lung function should undergo pulmonary testing to ascertain whether they will tolerate
single lung ventilation. If they are not able to tolerate
isolated lung ventilation, then cardiopulmonary bypass is
first instituted for intrathoracic preparation. The preoperative transesophageal echocardiogram (TEE) remains
the gold standard for peri-operative planning. It is important
2/7/2005, 1:44 PM
Indian Heart J 2004; 56: 618–621
Kypson et al. Robotically Assisted Cardiac Surgery 619
to correlate the dynamic echocardiographic anatomy with
both the Carpentier functional class and intraoperative
pathology. Coronary angiography should be done preoperatively in patients who are over 40 years old, have a
strong family history, or have symptoms of coronary artery
disease.
arm convergence avoids left atrial wall tearing during
instrument manipulations. A “high-magnification”
camera with a 30° (looking up) angulation is used and 3D
endoscope placed through the medial portion of the minithoracotomy. Fig. 1 depicts a typical set up of a robotic
mitral valve repair. The assistant uses the remainder of the
incision as a working port for needle and suture retrieval.
Surgical Techniques
Pre- and post-operative transthoracic and TEE studies
should be done in every patient. Patients are anesthetized
and positioned with the right chest elevated to 30° and with
the right arm tucked by the side. Single left-lung ventilation
is performed to facilitate pericardial, aortic, and cardiac
exposure. Cardiopulmonary bypass is established at 28°C
using femoral arterial inflow. Kinetic venous drainage is
provided using both a 21-23 F femoral-to-right atrial and
a right jugular vein (17 F) cannula. If the femoral artery is
too small or atherosclerotic, either a Bio-Medicus™
(Medtronic, Minneapolis, MN) or Directflow™ (Cardiovations, Inc., Somerville, NJ) transthoracic cannula can be
placed via a right anterior 2nd interspace port.
A 4 cm inframammary incision is used and the chest is
entered through the 4th intercostal space (ICS). Under
direct vision, the pericardium is opened 2 cm anterior to
the phrenic nerve and distracted laterally using
transthoracic sutures. Antegrade cardioplegia is given by
an aortic root needle/vent placed either under direct vision
or videoscopically. To minimize intracardiac air
entrainment, carbon dioxide is insufflated at 1-2 liters per
min via a 14 gauge plastic catheter. For aortic occlusion, a
transthoracic cross-clamp (Scanlan International Inc.,
Minneapolis) is passed through a 4 mm incision in the midaxillary 3rd ICS. The posterior tine of the clamp is passed
through the transverse sinus with care taken not to injure
the right pulmonary artery, left atrial appendage, left main
coronary, or aorta. Intermittent antegrade cold blood
cardioplegia is infused every 20 min to maintain cardiac
arrest and myocardial protection. After cardioplegic arrest,
a transthoracic left atrial roof retractor is used to expose
the mitral valve through a 3-4 cm left atriotomy made
medial to the right superior pulmonary vein. After valve
inspection, positions for da Vinci™ left and right arm port
incisions are determined. The right trocar is placed in the
5th ICS posterolateral to the incision and parallel to the
right inferior pulmonary vein. Occasionally, the 6th ICS
provides a better angle for the right robotic arm. The left
trocar is generally placed 6 cm cephalad and medial to the
right trocar, insuring internal clearance between arms to
avoid both external and internal conflicts. Optimal robotic
IHJ-763-04 review article.p65
619
Fig. 1. Typical set up for a robotic mitral valve repair. The robotic camera arm is
placed into the center of the 4 cm incision. Both robotic arms are placed through
the chest wall in a triangular fashion at least 5 cm apart to avoid any instrument
arm conflicts. A soft tissue retractor holds the incision open for the passing of
suture and tissue. The transthoracic aortic cross-clamp is placed in the midaxillary line, low enough so that there is no conflict with the left robotic arm.
The transthoracic atrial retractor is placed just off the lateral edge of the sternum,
avoiding the internal mammary artery.
Operative procedures are performed from the surgeon’s
console (Fig. 2). Annuloplasty bands (Edwards Lifesciences,
Irvine, CA) are used to support repairs or provide annular
reduction. Leaflet resections, sliding-plasties, papillary
muscle reconstructions, chord insertions or transpositions
can be readily performed because of the 3D high
magnification optics, camera mobility and flexible
instrument manipulation within both the atrium and
ventricle (Table 2). Each suture is placed and tied
intracorporeal. After completion of the repair, robotic arms
are removed, and the left atrium is closed under direct vision
to decrease operative times. Standard de-airing and
weaning procedures are performed under TEE control.
Clinical Results
East Carolina University sponsored a multi-center, phase II
FDA trial that studied 112 da Vinci™ patients operated in
10 United States centers.4 Repairs included quadrangular
resections, sliding-plasties, edge-to-edge approximations,
2/7/2005, 1:44 PM
Indian Heart J 2004; 56: 618–621
620 Kypson et al. Robotically Assisted Cardiac Surgery
Fig. 2. Complex robotic Barlow’s repair with a sliding annuloplasty of P3 and
chordal transfer to the anterior leaflet (CT-AL). Note P3 being cut with robotic
scissors. Because of the excellent visualization system, exposure of the chordal
structures of the mitral valve is relatively straightforward.
Table 2. Robotic mitral procedures (n=150)
Valve replacements
Valve repairs
Ring annuloplasty alone
Posterior leaflet resection
Sliding annuloplasty
Posterior/anterior cleft repair
Chordal replacements (GORE)
Chordal transfer
Alfieri
2 (1.3)
148 (98.7)
36 (24.0)
94 (62.7)
25 (16.7)
1 (0.67)
9 (6.0)
40 (26.7)
6 (4.0)
Values in parentheses are percentages
and both chordal transfers and replacements. Leaflet repair
and annuloplasty times had decreased to 37 and 39 min
respectively, compared to an earlier phase I trial. Aortic
cross-clamp and cardiopulmonary bypass times averaged
2.1 and 2.8 hours, respectively. There were little differences
in operative times between centers. At one-month followup, transthoracic echocardiography (TTE) revealed that 9
(8.0%) patients had ≥ grade 2 mitral regurgitation and 6
(5.4%) of these had re-operations. Although the reoperative
rate was of concern, the failed repairs were distributed
across the group evenly and some centers had performed
less than 10 robotic operations. There were no deaths,
strokes, or device-related complications. This study
demonstrated that multiple surgical teams could perform
robotic mitral valve surgery safely early in the development
of this technique albeit with a learning curve as far as
operative times and repair results are concerned. The device
was approved by FDA in November 2002 for use in mitral
valve surgery.
IHJ-763-04 review article.p65
620
We recently published results of our first 38 mitral valve
repairs with the da Vinci system.5 Patients were divided into
two cohorts of 19 patients each (early experience and late
experience) for data analysis and comparison. Total robotic
time represented the exact time of robot deployment after
valve exposure and continued until the end of annuloplasty
band placement. This time decreased significantly from
1.9±0.1 hours in the first group to 1.5±0.1 hours in the
second group (p=0.002). Concurrently, leaflet repair time
reduced significantly from 1.0±0.1 hours to 0.6±0.1 hours
(p=0.004). Also, the total operating time decreased
significantly from 5.1±0.1 hours to 4.4±0.1 hours in the
second group of patients. Further, both cross-clamp and
bypass times decreased significantly with experience.
Similar time trends were reported in a later publication that
reviewed our subsequent da Vinci™ patients.6 The only
time that did not change between the two groups was the
annuloplasty band placement time. Most likely, this
represents an inherent limitation in the current technology
of tying suture knots. Even with extensive experience, the
speed of suture placement is limited. For the entire group
of 38 patients, the mean length of hospital stay was 3.8
days, with no difference between the two groups. For all
patients in the study, 84% demonstrated a reduction of
three or more grades in mitral regurgitation at follow-up.
In the entire series there was no device-related complication
or operative death. One valve was replaced at 19 days
because of hemolysis secondary to a leak that was directed
against a prosthetic chord.
Fig. 3. Robotic ring annuloplasty. Note the use of nitinol U-clips™ on the
annuloplasty band. Annuloplasty band placement times have been significantly
reduced due to this innovation.
2/7/2005, 1:44 PM
Indian Heart J 2004; 56: 618–621
Kypson et al. Robotically Assisted Cardiac Surgery 621
To date, we have completed over 150 robotic mitral valve
repairs with the da Vinci system. There has been one
operative death (0.67%) from a protamine reaction but no
device-related complications. In the entire series there have
been two late deaths (1.3%) and we have reoperated on four
(2.7%) patients for mid-term valve repair failures. Even at
the 100th case we continued to see improving operative
time data. No doubt this is related to improved robot set up
and deployment times, closer team working relations, and
surgeon experience. However, there are parts of this
operation that can only be improved by new technology
and not experience alone. We have found that by using
alternative suturing techniques, such as nitinol U-clips™
(Coalescent Surgical, Sunnyvale, CA) annuloplasty band
insertion times are reduced by 50% (Fig. 3). Improved
methods for retraction and exposure as well as visioning
need to be developed. Moreover, to achieve the greatest
facility with robotics in mitral surgery, instrument arm sizes
must be reduced and a greater variety of end-effecter tips
developed. As our group has trained over 250 surgeons to
repair mitral valves using robotic techniques, we believe
that the true benefits will emerge over a larger population
and that many of these methods could become standard in
the future.
instruments are manipulated by computers. Recent
successes with direct vision, videoscopic, and robotic
minimally invasive surgery all have reaffirmed that this
evolution can be extremely fast, albeit through various
pathways.
Technological advances are occurring at a rapid pace.
In just a short span of six years, cardiac surgery has
witnessed the incorporation of robotic tele-manipulative
systems into the mitral surgeon’s armamentarium.
Nevertheless, surgical scientists must continue to evaluate
this technology critically in this new era of cardiac surgery.
Despite enthusiasm, caution cannot be overemphasized.
Surgeons must be careful as indices of operative safety,
speed of recovery, level of discomfort, procedural cost, and
long-term operative quality have yet to be defined fully.
Traditional valve operations still enjoy long-term success
with ever-decreasing morbidity and mortality, and remain
our measure for comparison. Ultimately, telerobotic systems
will continue to evolve, most likely creating a new paradigm
for the way cardiac surgery is performed in the 21st century.
Conclusions
The reported results suggest that robotic mitral surgery is
well on the way to reality. Although operative philosophies,
patient populations and surgeon abilities differ between
centers, the compendium of recent results remains very
encouraging. The advent of true three-dimensional vision
with tactile instrument feedback will be the final bridge to
truly “tele-micro-access” operations. Also, to perform these
operations optimally, “extracorporeal” surgeons and
engineers will need to improve methods by which
IHJ-763-04 review article.p65
621
References
1. Carpentier A, Loulmet D, Aupecle B, Kieffer JP, Tournay D, Guibourt
P, et al. Computer assisted open-heart surgery. First case operated
on with success. CR Acad Sci III 1998; 321: 437–442
2. Chitwood WR Jr, Nifong LW, Elbeery JE, Chapman WH, Albrecht R,
Kim V, et al. Robotic mitral valve repair: trapezoidal resection and
prosthetic annuloplasty with the da Vinci surgical system. J Thorac
Cardiovasc Surg 2000; 120: 1171–1172
3. Mehmanesh H, Henze R, Lange R. Totally endoscopic mitral valve
repair. J Thorac Cardiovasc Surg 2002; 123: 96–97
4. Nifong LW, Chitwood WR Jr, Argenziano M. Robotic mitral valve
surgery: a United States multi-center trial. J Thorac Cardiovasc Surg
(in press).
5. Nifong LW, Chu VR, Bailey BM, Maziarz DM, Sorrell Vl, Holbert D, et
al. Robotic mitral valve repair: experience with the da Vinci system.
Ann Thorac Surg 2003; 75: 438–443
6. Kypson AP, Nifong LW, Chitwood WR Jr. Robotic mitral valve surgery.
Semin Thorac Cardiovasc Surg 2003; 15:121–129
2/7/2005, 1:44 PM
622 Mishra
et al. Robotic Cardiac Surgery
Original
Article
Indian Heart J 2004; 56: 622–627
Robotically Enhanced Coronary Artery Bypass Surgery
YK Mishra, H Wasir, M Sharma, KK Sharma, Y Mehta, N Trehan
Departments of Cardiovascular Surgery and Cardiovascular Anesthesiology
Escorts Heart Institute and Research Centre, New Delhi
Background: Robotically enhanced telemanipulation surgery is a fast developing technique which allows totally
endoscopic cardiac surgery with utmost precision and perfection on both beating heart as well as arrested
heart.
Methods and Results: Between December 2002 and February 2004, 125 patients underwent robotically
enhanced coronary artery bypass surgery using the da Vinci telemanipulation system (Intuitive Surgical Inc.,
California). Eleven patients underwent totally endoscopic coronary artery bypass surgery. Of them 9 were done
on beating heart while 2 were done on arrested heart. One hundred and fourteen patients had endoscopic
takedown of internal mammary artery followed by minimally invasive direct coronary artery bypass in 63
patients and left anterolateral thoracotomy in 51 patients. The internal mammary artery mobilization time
was 42 min (35-74 min) while the left internal mammary artery to left anterior descending artery anastomosis
time ranged from 20 to 36 min for the totally endoscopic coronary artery bypass patients. In 1 patient, the right
internal mammary artery was anastomosed to diagonal artery totally endoscopically. The mean internal
mammary artery flow by Doppler measurement done in patients undergoing minimally invasive direct coronary
artery bypass was 64 ml/min. Seven patients required conversion to median sternotomy and coronary bypass
surgery on beating heart. The mean intensive care unit stay was 1.2 days and the mean hospital stay 4.5 days.
There was 1 in-hospital mortality. All 11 patients who underwent totally endoscopic bypass surgery had coronary
angiography done at 3 months interval which showed 100% patency in 10 patients while one patient had 50%
anastomotic narrowing for which coronary angioplasty was done in the same sitting.
Conclusions: Using telematic technology, a complete endoscopic anastomosis is possible in both single vessel
and suitable double vessel disease patients. The use of robotics is now extended to achieve complete myocardial
revascularization by harvesting both the internal mammary arteries and making a small thoracotomy for direct
anastomosis as well. (Indian Heart J 2004; 56: 622–627)
Key Words: Coronary artery bypass grafting, Coronary artery disease, Minimally invasive surgery
T
he ultimate goal of minimally invasive coronary artery
bypass grafting (CABG) is to perform the entire
anastomosis endoscopically. This is done by keeping the
following main concepts of minimally invasive surgery in
mind: firstly, to circumvent the deleterious effect of cardiopulmonary bypass (CPB); and secondly to minimize the
incision and surgical trauma. This also aims at reducing
patient’s morbidity, length of hospital stay and overall cost.
Minimally invasive direct coronary artery bypass (MIDCAB)
via a small ministernotomy approach or a 2" left anterior
thoracotomy approach, also termed as endoscopic
atraumatic coronary artery bypass (EndoACAB),1,2 refers
Correspondence: Dr Yugal K Mishra, Senior Consultant-Cardiac Surgeon
Escorts Heart Institure and Research Centre, Okhla Road, New Delhi 110025
e-mail: [email protected]
IHJ-694-04.p65
622
to such approaches. The advancement in beating heart
surgery also aided these approaches. In patients for
multivessel revascularization where direct aortovenous
cannulation is not possible through a limited incision, the
Port Access system via formal approach (Heartport, Inc,
Redwood City, California, USA) is very helpful for
establishing CPB.3-5
With the advent of robotically enhanced telemanipulation, the latest in minimally invasive technique
is now available thus permitting true closed chest totally
endoscopic procedures.6-9 Our institute initiated the robotic
programme using the da Vinci surgical system (Intuitive
Surgical Inc, California, USA) in December 2002. We review our experiences with the use of da Vinci in performing
CABG using various minimally invasive approaches.
2/7/2005, 1:44 PM
Indian Heart J 2004; 56: 622–627
Mishra et al. Robotic Cardiac Surgery 623
Methods
Between December 2002 and February 2004, 125 patients
underwent robotically enhanced CABG. Eleven patients
underwent totally endoscopic coronary artery bypass
(TECAB). Of them, 9 were done on beating heart while 2
were done on arrested heart using the Port Access system.
Ten patients who underwent TECAB had single vessel left
anterior descending (LAD) disease, while 1 patient had
single vessel disease with additional proximal diagonal
artery disease for which anastomosis was done using the
right internal mammary artery (RIMA) on beating heart.
One hundred and fourteen patients underwent
EndoACAB in which the skeletonized internal mammary
artery was harvested in its entire length robotically and
direct anastomosis was done either by MIDCAB (n=63) or
using a small anterior thoracotomy incision (THORACAB)
(n=51). All patients were informed about the procedure preoperatively and each patient gave a written informed
consent; institutional review board permission was also
obtained. The 125 patients (108 males, 17 females) were
58.4±.8.0 years old (range: 34-78 years). The pre-operative
demographic profile is listed in Table 1. Left ventricular
ejection fraction (LVEF) was 54±2.8% and New York Heart
Association (NYHA) class was 2.1±0.6. The pre-requisite
for patients included for any robotic procedure were: those
requiring CABG, age range 18-80 years and informed
consent for the procedure.
Patients with significant co-morbidity including
compromised pulmonary function tests, those requiring
additional cardiac procedures, LVEF < 30%, associated
ventricular or aortic aneurysm or those with significant
peripheral vascular disease, thus making them unfit for Port
Access procedures, were not considered for robotic surgery.
Other pre-operative exclusion criteria included, body mass
index (BMI) >35.0 kg/m 2, decompensated congestive
heart failure (NYHA class III or IV), acute pulmonary
edema, uncontrolled hypertension, any coagulopathy or
history of acute myocardial infarction (MI) of <30 days
duration.
Intraoperatively, if any of the following criteria were
found, the procedure was converted to conventional CABG
on beating heart i.e. systolic arterial pressure drop of >20%
of baseline or <80 mmHg for >15 min or not responding
to therapy, dense pleural or pericardial adhesions limiting
visibility, intramyocardial LAD or target LAD diameter <1.5
mm previously not identified on coronary angiogram or
inadequate visualization or malpresentation of target vessel
such that it was not accessible via routine endoscopic ports.
Anesthesia for TECAB: After routine induction of
anesthesia, patients underwent double lumen intubation
for single right lung ventilation. Arterial cannulation was
done using both radial and femoral arteries. Bilateral radial
cannulation was done for invasive monitoring of the
endoaortic occlusion catheter in patients who underwent
TECAB on arrested heart. All patients had thermodilution
pulmonary artery catheter monitoring and transesophageal echocardiography (TEE) for assessment of cardiac
function and for positioning and monitoring the endoaortic
catheter of the Port Access system.
The da Vinci Surgical System: The da Vinci telemanipulation system consists of a master console (Fig. 1)
used by the operating surgeon for controlling the microinstruments which are mounted on the surgical cart which
has three arms (slave unit, Fig. 2). The surgical assistant
manages the change of instruments and positions of the
arms and camera on the slave unit. Of the three arms, the
left and right arms carry the microinstruments resembling
the human wrist which correspond to the left and right
Table 1. Pre-operative demographic profile (n=125)
Age (range) (years)
Male
Female
NIDDM
Hypertension
Smoking
COPD
LVEF
Stable angina
Previous MI
NYHA class (mean)
58.4±8.0 (34-78)
108 (86.4)
17 (13.6)
32 (30.0)
51 (48.0)
26 (24.5)
7 (6.6)
54 ± 2.8
54 (51.0)
11 (10.3)
2.1 ± 0.6
Values in parentheses are percentages
NIDDM: non-insulin dependent diabetes mellitus; COPD: chronic
obstructive pulmonary disease; LVEF: left ventricular ejection fraction;
MI: myocardial infarction; NYHA: New York Heart Association
IHJ-694-04.p65
623
Fig. 1. Robotic master console.
2/7/2005, 1:44 PM
Indian Heart J 2004; 56: 622–627
624 Mishra et al. Robotic Cardiac Surgery
Fig. 2. Robotic cart or slave unit.
Fig. 3. Robotic skeletonized left internal mammary artery dissection.
arms on the main console. The middle arm carries a stereo
endoscope for three-dimensional vision seen at the console
end. An additional video cart carries the light source, a
continuous carbon dioxide (CO 2) insufflator, and a
conventional two-dimensional monitor for viewing by the
surgical team.
The video image from the camera is transferred to the
master console, magnified (×10), and projected as a threedimensional image for optimal visualization.
In the case of beating heart surgery once the internal
mammary artery (IMA) is harvested, the endostabilizer is
inserted via a 4th port in the xiphoid area under endoscopic
vision. The patient is thereafter heparinized and the IMA
prepared for anastomosis. Throughout the procedure, the
CO2 pressure is kept between 10-14 mmHg depending on
the working space, at the same time monitoring the systolic
pressure for any hemodynamic instability.
Once the LAD is opened the anastomosis is done either
by using continuous endoscopic suture or by using
endoclips (US Surgical Corp., Connecticut, USA) (Fig. 4).
After completion of anastomosis the endoaortic occlusion
catheter is deflated and patient weaned from CPB. Heparin
is reversed using protamine and a single chest tube is placed
via the xiphoid port which is guided into the left pleural
cavity.
In patients for whom MIDCAB or EndoACAB was
performed to LAD the approach was either via a small
Operative Technique for TECAB: The approach for both
left internal mammary artery (LIMA) and the RIMA can
be done from the left pleural cavity. The patient is placed in
supine position with the left chest elevated to about 30°.
The landmarks such as suprasternal notch, xiphoid and
2nd to 6th ribs are marked. After ensuring single right lung
ventilation the camera cannula with CO2 insufflator port
is inserted in 4th or 5th intercostal space close to the
anterior axillary line and chest is insufflated with warm
CO2 at 37°C. After insertion of the endoscope, two ports
are placed under visual control to accommodate the two
robot arms, usually in the 2nd and 6th intercostal space.
LIMA is harvested, skeletonized right from its origin from
left subclavian artery upto its bifurcation using a 30° angled
endoscope facing upward (Fig. 3). Unipolar cautery is used
at low intensity for the LIMA branches. RIMA can be
approached via the same ports after creating a retrosternal
mediastinal plane and opening the right pleura. The
pericardium is then opened using the same endoscope with
a 30° down angulation for visualization of the LAD and its
target site for anastomosis. If TECAB is proposed on arrested
heart then the Port Access system is used to initiate CPB
and infusion of antegrade cardioplegia into the aortic root
via the Port Access Endo clamp provides reliable cardiac
arrest.
IHJ-694-04.p65
624
Fig. 4. Robotic LIMA to LAD anastomosis using endoclips.
LIMA: left internal mammary artery; LAD: left anterior descending artery
2/7/2005, 1:44 PM
Indian Heart J 2004; 56: 622–627
Mishra et al. Robotic Cardiac Surgery 625
ministernotomy or a 2.5" left anterior thoracotomy incision
after a robotic takedown of skeletonized LIMA. Once the
anastomosis was completed, but prior to protamine
reversal, the LIMA flow was checked by Doppler flow
method for all patients.
Results
Of the 125 patients who underwent robotic enhanced
CABG, 11 patients underwent TECAB. Nine TECAB were
done on beating heart of which 8 were for single vessel LAD
disease and 1 was done for single vessel disease in which
RIMA was anastomosed to diagonal and LIMA to LAD on
beating heart. In 114 patients, the LIMA or RIMA was
harvested robotically in a skeletonized fashion. Of these,
51 underwent THORACAB via a small left anterior
thoractomy incision. In TECAB patients the total operating
time was 208±36 min in which, the LIMA was mobilized
in 42 min (range: 35-74 min) and the LIMA to LAD
anastomosis time ranged from 20-36 min. The LIMA
mobilization time range was same for the other patients.
Table 2 shows the various intraoperative parameters. Seven
patients had to be converted to conventional CABG. None
of these were from the TECAB group. Of these 5 patients
had dense pleural adhesions and 2 patients developed
hemodynamic instability not responding to medical
treatment. In both patients there was a fall in systolic blood
pressure with a rise in pulmonary artery pressure and a
fall in oxygen saturation which was due to high CO 2
insufflation pressures. There was no electrocardiographic
(ECG) ST-T change or arrhythmia and once the patient was
put back to two-lung ventilation, all hemodynamic parameters became stable. All 7 patients had regular
sternotomy and CABG was done on beating heart. No
Table 2. Intra-operative data
Duration (min)
Range (min)
OR time
CPB time
Cross clamp time
IMA mobilization time (TECAB)
LAD identification/dissection time
LIMA-LAD anastomosis time (TECAB)
RIMA-diag anastomosis time (TECAB)
208 ± 36
64
44
42
1.7
32
190 - 296
35-74
1-3
20-36
-
IMA flow (MIDCAB)
Pulsatility index (MIDCAB)
Conversion to median sternotomy
and OPCAB (MIDCAB)
64 ml/min
2.1
36-78 ml/min
1.4-3.6 (N<5)
7
-
OR: operating room; CPB: cardiopulmonary bypass; IMA: internal mammary artery;
TECAB: totally endoscopic coronary artery bypass; LAD: left anterior descending
artery; LIMA: left internal mammary artery; RIMA: right internal mammary artery;
diag: diagonal artery; OPCAB: off-pump coronary artery bypass; MIDCAB: minimally
invasive direct coronary artery bypass
IHJ-694-04.p65
625
conversion for any hemodynamic instability has, however,
been done in the last 90 cases.
The post-operative parameters are summarized in
Table 3. One patient developed superficial infection of the
anterior thoracotomy site which responded to antibiotics.
Three patients who had underwent MIDCAB were reexplored for bleeding. Re-exploration was done via the same
limited incision. In two patients the bleeding was from
mammary branch; however, in the third patient no specific
bleeding site was found. There was one mortality in the nonTECAB group. This patient, a known case of cholelithiasis,
had undergone MIDCAB, and developed fulminant gall
stones pancreatitis post-operatively.
Follow-up data is summerized in Table 4. All the patients
who underwent TECAB had an angiogram on follow-up at
3 months. Of the 11 TECAB patients, there was 100%
anastomotic patency (Fig. 5) in 10 patients while one
patients had 50% anastomotic narrowing for which
angioplasty was done at the same sitting. All 7 patients who
have completed one-year follow-up are symptom-free
during regular physical activity.
Discussion
The treatment of single vessel coronary artery disease is
generally non-surgical. However, when surgery is indicated
in patients with double vessel disease and a suitable
anatomy, one always wants the least invasive procedure
Table 3. Post-operative data
Total ventilation time (hours)
Chest tube drainage (ml)
ICU stay (days)
Hospital stay (days)
Peri-operative MI (CPK-MB > 10% of CPK
at 6 hours post-operative sample)
Reoperation for bleeding
New onset atrial fibrillation
Wound infection
Mortality
4.36
164 (55-360)
1.2
4.5
Nil
3
Nil
1
1
ICU: intensive coronary unit; MI: myocardial infarction
Table 4. Follow-up data
Duration
Late mortality
Recurrence of angina
Patient follow-up
TECAB
Rest
Post-operative angiogram (3 month)
LIMA - LAD patency
1-14 month
Nil
Nil
100%
92.6%
11
10
LIMA: left internal mammary artery; TECAB: totally endoscopic coronary
artery bypass; LAD: left anterior descending artery
2/7/2005, 1:44 PM
Indian Heart J 2004; 56: 622–627
626 Mishra et al. Robotic Cardiac Surgery
Fig. 5. Post-operative scar in TECAB patient.
TECAB: totally endoscopic coronary artery bypass
with smaller incision to minimize surgical trauma, improve
cosmesis, reduce risk of infection and produce least postoperative pain. With MIDCAB and off-pump coronary
artery bypass (OPCAB) techniques, the morbidity has
reduced compared to the conventional CABG on CPB. With
development of femoral Port Access technology for
peripheral CPB induction, the skin incision could further
be reduced 10,11 (Fig. 5). It was TECAB using robotic
telemanipulators which finally revolutionized the
minimally invasive techniques of CABG.6,8 If done on the
arrested heart, the Port Access technique is mandatory. Our
experience with Port Access surgeries which we have been
routinely performing for atrial septal defect (ASD) closure
and mitral valve surgery was helpful, as was our experience
on beating heart surgery which we are now routinely
applying for most CABGs. Our CPB time of 64 min and cross
clamp time of 44 min is comparable with other centers
which are performing TECAB mostly on arrested heart.6
We believe that there should be a low threshold for
conversion to open technique in the intial stages of robotic
surgeries to reduce the patient’s risk. Although pleural as
well as pericardial adhenolysis is very much possible but
unless sufficient experience with this technique is gained,
it should be avoided.
Adequate port placement was possible in all patients.
However, as each patient has a different chest anatomy,
proper marking of port sites is of utmost importance to
avoid unnecessary struggle due to instrument collision and
inability for complete IMA takedown due to left shoulder
or subcostal interference. This is more so in patients who
have medium-sized chest cavities, or extremely obese males,
or females with large breasts. In our view, these are the
patients who will benefit from an endoscopic procedure,
IHJ-694-04.p65
626
because risk of wound infection is almost nil with this
procedure, as seen in our series. The feasibility and safety
of closed chest IMA takedown has been shown by several
other groups.7,12,13 Although the use of TECAB can be
extended to patients with double vessel disease, as done in
one of our patients where RIMA was anastomosed to a large
diagonal, a suitable anatomy is a must before going ahead.
Dogan et al.6 reviewed their experience with double vessel
disease using both isolated IMAs and as sequential
anastomosis.9
Bilateral IMA grafting is feasible but appears to be
challenging and time consuming, therefore it has a very
limited indication. The use of multidetector computerized
tomographic (CT) scanning in determining the exact
position of coronary target site and size for anastomosis
using TECAB has also been reported.6
Although all our patients were ambulated by the 1st
post-operative day and most were fit for discharge by the
2nd post-operative day, as a protocol they were discharged
by the 4th post-operative day and came for first follow-up
on the 7th post-operative day.
The ultimate success of the Robotic procedure is a
combined effort of the surgeon at the console, the assistant
surgeon at the slave cart, the anesthesiologist and the
perfusionist who all need to work as a team with
communication at every stage. From the change of
instruments to hemodynamic monitoring, the CO 2
pressures and routine blood gas monitoring all require
utmost vigilance at all times to perform this minimally
invasive procedure to perfection.
The hemodynamics of single lung ventilation and
anesthesiologic management of all patients undergoing
robotic surgery is an emerging domain in cardiac
anesthesia.14 Hypotension, which is secondary to raised
intrathoracic pressure due to CO2 insufflation, needs to be
controlled meticulously.
Although most centers continue to perform TECAB on
arrested heart, it is yet premature to comment on the
quality of anastomosis on beating versus arrested heart.
With our experience in beating heart surgery and results
of beating heart TECAB, we do believe that TECAB done on
beating heart is a safe option which circumvents all the
deleterious effects of CPB especially if used as a new
procedure. As in all other upcoming technologies, the
learning curve is gradual, a word of caution is a must for
all beginners.
With passage of time, the present limitations of the
system such as additional degree of freedom inside the chest
cavity, an additional support of the beating heart and
approachability to different target vessels will be overcome.
2/7/2005, 1:44 PM
Indian Heart J 2004; 56: 622–627
Mishra et al. Robotic Cardiac Surgery 627
The addition of the third arm and the next version of robotic
to provide vibrotactile sensations while grasping and
suturing will be a step ahead in the developing technology.
Conclusions: The use of telematic technology is feasible
for performing CABG on arrested as well as beating heart
with good post-operative results. This can also be extended
to achieve complete myocardial revascularization by
bilateral robotic IMA takedown and direct anastomosis via
small thoracotomy.
References
1. Talwalkar NG, Cooley DA. Minimally invasive cardiac artery bypass
grafting: a review. Cardiol Rev 1998; 6: 345–349
2. Diegeler A. Left internal mammary artery grafting to left anterior
descending coronary artery by minimally invasive direct coronary
artery bypass approach. Curr Cardiol Rep 1999; 1: 323–330
3. Groh M, Grossi EA. Multivessel coronary bypass grafting with
minimal access using cardiopulmonary bypass. Curr Cardiol Rep
1999; 1: 331–334
4. Wimmer-Greinecker G, Matheis G, Dogan S, Aybek T, Mierdl S, Kessler
P, et al. Patient selection for Port-Access multi vessel revascularization. Eur J Cardiothorac Surg 1999; 16 (Suppl 2): S43–S47
5. Wimmer-Greinecker G, Matheis G, Dogan S, Aybek T, Kessler P,
Westphal K, et al. Complications of port-access cardiac surgery. J
Card Surg 1999; 14: 240–245
6. Dogan S, Aybek T, Andressen E, Byhahn C, Mierdl S, Westphal K, et
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Groh MA, Sutherland SE, Burton HG 3rd, Johnson AM, Ely SW. Portaccess coronary artery bypass grafting: technique and comparative
results. Ann Thorac Surg 1999; 68: 1506–1508
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RE, et al. First report of the Port Access International Registry. Ann
Thorac Surg 1999; 67: 51–56
Falk V, Diegeler A, Walther T, Loscher N, Vogel B, Ulmann C, et al.
Endoscopic coronary artery bypass grafting on the beating heart
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Forum 1999; 2: 199–205
Falk V, Gummert JF, Walther T, Hayase M, Berry GJ, Mohr FW. Quality
of computer enhanced totally endoscopic coronary bypass graft
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Mehta Y, Gupta A. Robotic surgery and anesthesia. The Indian
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2/7/2005, 1:44 PM
628 Goswami
et al.
Original
Article
Indian Heart J 2004; 56: 628–635
Predictors of Left Atrial Appendage Clot
Predictors of Left Atrial Appendage Clot: A Transesophageal Echocardiographic Study of Left
Atrial Appendage Function in Patients with
Severe Mitral Stenosis
Kewal C Goswami, Rakesh Yadav, Vinay K Bahl
Department of Cardiology, Cardiothoracic Sciences Centre, All India Institute of Medical Sciences, New Delhi
Background: The purpose of this study was to prospectively evaluate a large group of consecutive, nonanticoagulated patients with severe rheumatic mitral stenosis and to analyze the left atrial appendage function
in relation to left atrial appendage clot and spontaneous echo contrast formation.
Methods and Results: We prospectively studied left atrial appendage function in 200 consecutive patients
with severe mitral stenosis who underwent transesophageal echocardiography and correlated it with spontaneous echo contrast and left atrial appendage clot. The mean age was 30.2±9.4 years. Fifty-five (27.5%) patients
were in atrial fibrillation. Left atrial appendage clot was present in 50 (25%) patients and 113 (56.5%) had
spontaneous echo contrast. The older age, increased duration of symptoms, atrial fibrillation, spontaneous
echo contrast, larger left atrium, depressed left atrial appendage function and type II and III left atrial appendage
flow patterns correlated significantly (p<0.05) with the left atrial appendage clot. Left atrial appendage ejection
fraction was significantly less in patients with clot (21.8±12.8% v. 39.1±13.2%, p<0.0001) and in those
with spontaneous echo contrast (30.3±16.2 % v. 40.3±11.8%, p<0.001). Left atrial appendage filling
(18.0±11.7 v. 27.6±11.8 cm/s, p <0.0001) and emptying velocities (15.4±7.0 v. 21.5±9.6 cm/s, p<0.001)
and filling (1.4±1.0 v. 2.5±1.4 cm, p<0.0001) and emptying (1.5±1.2 v. 2.1±1.2 cm, p <0.05) velocity time
integrals were also significantly lower in patients with clot as compared to those without clot. On multivariate
regression analysis, atrial fibrillation (odds ratio 6.68, 95% CI 1.85-24.19, p=0.003) and left atrial appendage
ejection fraction (odds ratio 1.06, 95% CI 1.00 - 1.11, p = 0.04) were the only two independent predictors of
clot formation. Incidence of clot was 62.5% in patients with left atrial appendage ejection fraction ≤25% as
compared to 10.4% in those having left atrial appendage ejection fraction >25%. Similarly patients with
spontaneous echo contrast had lower filling (21.7±11.5 v. 29.4±12.7 cm/s, p <0.0001) and emptying (17.0±8.1
v. 23.9±10.9 cm/s, p <0.0001) velocities, as well as filling (1.9±1.3 v. 2.7±1.3 cm, p<0.01) and emptying
(1.7±1.0 v. 2.3±1.4 cm, p<0.01) velocity time integrals as compared to patients without spontaneous echo
contrast. In a subgroup of the patients with normal sinus rhythm, the left atrial appendage ejection fraction
was significantly less in patients with clot compared to those without clot (31.2±13.2 v. 41.3±11.5 %, p <0.01).
Conclusions: In the patients with severe mitral stenosis, besides atrial fibrillation, a subgroup of patients in
normal sinus rhythm with depressed left atrial appendage function (left atrial appendage ejection fraction
≤ 25%) had a higher risk of clot formation in left atrial appendage and these patients should be routinely
anticoagulated for prevention of clot formation. (Indian Heart J 2004; 56: 628–635)
Key Words: Mitral stenosis, Left atrial appendage function, Left atrial clot
T
he incidence of thromboembolic complications is
higher in patients with rheumatic mitral stenosis
Correspondence: Dr Kewal C Goswami, Additional Professor of
Cardiology, Cardiothoracic Sciences Centre, All India Institute of Medical
Sciences, New Delhi 110029.
IHJ-757-04.p65
628
specially in those with atrial fibrillation (AF)1-4 and there is
general consensus that prophylactic anticoagulation is
needed in this subset of patients. Left atrial appendage
(LAA) is the most common site of clot formation.5-8 During
the last decade, the focus was on the presence of left atrial
2/7/2005, 1:45 PM
Indian Heart J 2004; 56: 628–635
spontaneous echo contrast in patients with rheumatic
valvular disease and non-rheumatic AF and many studies
have shown it as an independent marker of thrombus
formation and thromboembolic episodes.4,6,9-16 LAA had
been the site of great interest because of its predilection for
spontaneous echo contrast and clot formation. Several
studies have evaluated its mechanical and flow dynamics
and correlated with the clot formation, spontaneous echo
contrast and thromboembolic risk in patients with
rheumatic valvular diseases,16-19 non- rheumatic AF20-23
and various cardiomyopathies.24 However, previous studies
evaluating patients with mitral stenosis were either too
small or included a heterogenous group of mitral valve
disease patients consisting of the whole spectrum of mitral
stenosis severity, patients with associated mitral regurgitation and patients who were on anticoagulation.18,19,25 The
purpose of this study was to evaluate prospectively a large
group of consecutive, non-anticoagulated patients with
severe rheumatic mitral stenosis and to analyze the LAA
function in relation to LAA clot and spontaneous echo
contrast formation.
Methods
Study patients: Two hundred consecutive patients with
severe mitral stenosis (mitral valve area ≤ 1 cm2) being
evaluated for percutaneous transvenous mitral
commissurotomy (PTMC), were studied in our institute, a
tertiary-care referral centre in north India. All clinical and
echocardiographic data were collected prospectively.
Patients with associated > 2/4 mitral regurgitation,
significant aortic valve disease, previous closed mitral
valvotomy and those on anticoagulation or antiplatelet
therapy were excluded. Twenty age-matched patients with
cerebrovascular accidents who underwent transesophageal
echocardiographic study and who were free of heart
disease, hypertension and diabetes, were taken as controls.
Goswami et al. Predictors of Left Atrial Appendage Clot 629
patients with normal sinus rhythm, the maximum area of
LAA (LAAmax) was measured just before the P wave and
minimum area of LAA (LAAmin) was measured at or just
after the QRS complex at the end of LAA systole, by
planimetry. The perimeter extended from the tip of the
limbus between the upper left pulmonary vein along a
straight line drawn to the aorta at its shortest point at the
base of LAA. The LAA area was calculated from the
computer- assisted table of the echocardiographic machine.
In patients with AF the maximum and minimum
appendage area were not related to QRS. In these cases
maximum and minimum areas were obtained independent
of the electrocardiogram (ECG) in each cardiac cycle. An
average of 5 readings was taken in patients with AF and 3
for normal sinus rhythm (NSR).
LAAmax - LAAmin
LAA ejection fraction =
LAAmax
The LAA blood flow velocities were obtained by placing
the pulsed Doppler sample volume into the outlet of the
appendage ≥1 cm away from the LA cavity. Three different
types of LAA flow patterns were analyzed. Type I flow was
characterized by a biphasic flow of clearly defined waves
(Figs 1 and 2). Type II flow was characterized by saw tooth
morphology (Fig. 3), whereas in type III flow (Fig. 4) there
were no identifiable flow waves (i.e., absolutely no flow
recorded despite minimal velocity scale and minimal wall
filter, or a minor flow with velocity <10 cm or spontaneous
echo contrast).
LAA clot was diagnosed by the presence of clearly
defined echogenic intracavitary mass with an echo texture
different from that of the underlying endocardium and not
due to the pectinate muscle as described by us earlier.8
Transthoracic echocardiography (TTE): The
transthoracic studies were done by standard techniques
using a Hewlett Packard Sonos 1500 machine with 3.5
MHz transducer. Left atrial diameter was taken in the
parasternal long axis view in M-mode at end-systole. Left
atrial end-systolic area on 2D echocardiography was taken
in two views (parasternal long axis and apical 4-chamber
views) and these two values were averaged.
Transesophageal echocardiography (TEE): TEE was
performed after TTE on the same day in all cases as described
by us earlier.8 A 5 MHz transducer with capacity for pulsed
Doppler (Hewlett Packard omniplane probe) was used. In
IHJ-757-04.p65
629
Fig. 1. Pulse Doppler transesophageal recording of the type I flow pattern at
the outlet of left atrial appendage in a normal control.
2/7/2005, 1:45 PM
Indian Heart J 2004; 56: 628–635
630 Goswami et al. Predictors of Left Atrial Appendage Clot
Spontaneous echo contrast was diagnosed by the presence
of dynamic smoke-like echoes in the LAA with a
characteristic swirling motion distinct from white noise
artefact after properly adjusting the gain settings. All
studies were reviewed independently by two experienced
observers and any discrepancy was resolved by consensus.
Fig. 2. Pulse Doppler transesophageal recording of the type I flow pattern at
the outlet of left atrial appendage in a patient with severe mitral stenosis and
normal sinus rhythm.
Statistical analysis: Data are presented as mean ± SD.
For comparison, unpaired student's t test was used for
continuous variables and Chi-square test for categorical
variables and values were considered significant when p
value was <0.05. Univariate, multivariate logistic regression analysis and discriminant function analysis were
done for all the variables to determine the factors that
independently predict the presence of clot and spontaneous
echo contrast.
Results
The mean age of the patients was 30.2 ± 9.4 years (range
13-60 years); 97 (48.5%) patients were males. Mean
duration of symptoms was 32.0 ± 27.6 months (range 1180 months). One hundred and eighteen (59%) patients
were in New York Heart Association (NYHA) class II, 75
(37.5%) in class III, and 7 (3.5%) in class IV. The baseline
patient characteristics and its comparison with controls are
shown in Table 1. The LA size and LAA area were
significantly more and the LAA ejection fraction, emptying
and filling velocities and their respective velocity time
integrals (VTIs) were significantly less in patients with
mitral stenosis as compared to controls.
Fig. 3. Pulse Doppler transesophageal recording of the type II flow pattern at
the outlet of left atrial appendage in a patient with severe mitral stenosis and
atrial fibrillation.
Fig. 4. Pulse Doppler transesophageal recording of the type III flow pattern at
the outlet of left atrial appendage in a patient with severe mitral stenosis.
IHJ-757-04.p65
630
Clinical and echocardiographic variables in relation
to LAA clot (Tables 1 and 2): The age, duration of
symptoms and LA size (both area and diameter) were
significantly more in patients with clot. The mitral valve
area and mean diastolic gradient were not significantly
different in the two groups. The incidences of AF and
spontaneous echo contrast were significantly higher in
patients with clot (p<0.0001 for both). The LAAmax was
significantly more (p<0.0001) and ejection fraction was
significantly less (p<0.0001) in patients with clot as
compared to those without clot. The LAA peak emptying
(p<0.001) and filling (p<0.0001) velocities and emptying
(p<0.05) and filling (p<0.0001) VTIs were significantly
lower in patients with clot as compared to those without
clot. Patients with type II and type III flow patterns had
higher incidence of LAA clot (58.3% and 71.4%,
respectively) as compared to patients with type I flow
pattern (9.8%, p <0.0001).
After including all clinical and LAA function variables
2/7/2005, 1:45 PM
Indian Heart J 2004; 56: 628–635
Goswami et al. Predictors of Left Atrial Appendage Clot 631
Table 1. Baseline parameters and left atrial appendage function in patients with severe mitral stenosis and its comparison
with controls and patients with and without clot
Variables
Controls
(n=20)
MS patients
(n=200)
p value*
Patients with
clot (n=50)
Patients without
clot (n=150)
p value #
Age (years)
Symptom duration (months)
MVA (cm2)
MDG (mmHg)
LA diameter (mm)
LA area (cm2)
Rhythm
AF
NSR
SEC
Present
Absent
LAA max area (cm2)
LAA - EF (%)
LAA emptying velocity (cm/s)
LAA filling velocity (cm/s)
LAA emptying VTI (cm)
LAA filling VTI (cm)
28.9±6.6
28.0±5.8
13.0±2.1
30.2±9.4
32.0±27.6
0.79±0.15
15.6±6.3
49.4±8.01
31.9±10.0
NS
<0.0001
<0.0001
34.5±11.3
42.5±38.3
0.77±0.14
14.7±6.0
53.7±8.4
39.3±12.4
28.8±8.1
28.4±21.9
0.81±0.15
15.9±6.3
47.8±7.3
29.5±7.6
<0.001
<0.005
NS
NS
<0.0001
<0.0001
0
20
55 (27.5%)
145 (72.5%)
<0.0001
<0.0001
34 (61.8%)
16 (11.0%)
21 (38.2%)
129 (89.0%)
<0.0001
<0.0001
0
20
2.8± 0.7
61.1± 10.2
46.6±18.3
46.2±21.6
3.4± 1.3
4.4± 2.1
113 (56.5%)
87 (43.5%)
6.0±2.4
35.8±15.6
20.1±9.9
25.1±12.5
1.91±1.23
2.2±1.4
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
41 (36.3%)
9 (10.3%)
7.3±3.0
21.8±12.8
15.4±7.0
18.0±11.7
1.5±1.2
1.4±1.0
72 (63.7%)
78 (89.7%)
5.6±1.9
39.1±13.2
21.5±9.6
27.6±11.8
2.1± 1.2
2.5± 1.4
<0.0001
<0.0001
<0.0001
<0.0001
<0.001
<0.0001
<0.05
<0.0001
AF: atrial fibrillation; EF: ejection fraction; LA: left atrium; LAA: left atrial appendage; max: maximum; MDG: mean diastolic gradient; MS: mitral stenosis; MVA: mitral valve
area; NS: not significant; NSR: normal sinus rhythm; SEC: spontaneous echo contrast; VTI: velocity time integral
* When patients with mitral stenosis were compared with controls. #When patients with and without clot were compared.
Table 2. Types of appendage flow pattern and its relation with left atrial appendage function, spontaneous echo contrast
and left atrial appendage clot
Parameters
Type I
(n=143)
Type II
(n=36)
Type III
(n=21)
p value
I v. II
p value
I v. III
p value
II v. III
LA diameter (mm)
LA area (cm2)
LAA max area (cm2)
LAA - EF (%)
LAA emptying velocity (cm/s)
LAA filling velocity (cm/s)
LAA emptying VTI (cm)
LAA filling VTI (cm)
Rhythm
AF
NSR
SEC
Present
Absent
Clot
Present
46.9±6.4
28.4±6.9
5.5±2.0
40.5±12.3
22.4±9.8
28.6±11.7
2.1±1.2
2.6±1.3
54.2±9.7
39.9±12.2
7.2±2.6
23.7±7.5
16.4±7.0
19.2±8.4
1.7±1.1
1.8±1.1
57.1±5.4
42.0±9.6
7.6±3.1
12.5±8.2
8.1±2.0
8.3±1.8
0.6±0.3
0.5±0.19
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
NS
NS
NS
<0.001
<0.05
<0.01
<0.05
<0.01
0
143
36
0
19
2
<0.0001
<0.0001
<0.0001
<0.0001
NS
NS
63
80
31
5
19
2
<0.0001
<0.0001
<0.0001
<0.0001
NS
NS
14
21
15
<0.0001
<0.0001
NS
129
15
6
<0.0001
<0.0001
NS
Absent
AF: atrial fibrillation; EF: ejection fraction; LA: left atrium; LAA: left atrial appendage; max: maximum; NS: not significant; NSR: normal sinus rhythm; SEC: spontaneous echo
contrast; VTI: velocity time integral
in multivariate logistic regression analysis, AF [odds ratio
(OR) 6.68, 95% CI 1.85 - 24.19, p=0.003] and LAA
ejection fraction (OR 1.06, 95% CI 1.00 - 1.11, p = 0.04)
were found to be independently related to the presence of
clot in LAA and when LAA ejection fraction of 25% was
arbitrarily taken as a cut off point, 62.5% (35/56) patients
IHJ-757-04.p65
631
with LAA ejection fraction ≤ 25% had clot (6 times more)
as compared to 10.4% (15/144) patients with LAA ejection
fraction > 25% (p<0.0001).
On discriminant function analysis two variables i.e. AF
and LAA ejection fraction, turned out to be the most
important variables to discriminate the two groups. The
2/7/2005, 1:45 PM
Indian Heart J 2004; 56: 628–635
632 Goswami et al. Predictors of Left Atrial Appendage Clot
derived discriminate equation is :
D = 0.392 + { (-0.027 × LAA ejection fraction %) +
(2.134 ×1 if AF is present and 0 if AF is absent)}
Where if D is > 0, the predictive group was with clot and if
< 0 then the predicted group was without clot with an
accuracy of 80.5%.
In the subgroup of patients with NSR (Table 3), larger
LA size and lower LAA ejection fraction were significantly
associated with LAA clot. In this subgroup, when LAA
ejection fraction of 25% was arbitrarily taken as a cut off
point, 50% (8/16) patients with LAA ejection fraction
≤ 25% had clot (8 times more) as compared to 6.2%
(8/129) patients with LAA ejection fraction > 25%. Though
maximum LAA size was larger and peak filling and
emptying velocities and their respective VTIs were lesser in
patients with clot, but they did not reach statistical
significance.
LAA Doppler flow patterns and LAA function: Type I
flow was present in 143 (71.5 %) patients and all were in
NSR. Type II flow was present in 36 (18%) cases and all
were in AF. Type III flow was observed in 21 (10.5%) cases,
NSR was noted in 2 (both were having large LAA clot
occupying whole of the LAA) and rest were in AF. LAA
function with respect to LAA ejection fraction, peak filling
and emptying velocities and VTIs were significantly
different between type I, type II and type III flow patterns.
Type III flow pattern had the lowest LAA ejection fraction
and peak velocities as compared to type I and type II. The
LAA clot and spontaneous echo contrast were significantly
more in patients with type II and type III flow patterns as
compared to type I (Table 2).
LAA function in relation to the presence of spontaneous echo contrast (Table 4): Spontaneous echo
contrast was present in 113 patients. LAA area was significantly more and LAA ejection fraction was significantly
less in the patients with spontaneous echo contrast as
compared to patients without spontaneous echo contrast.
The LAA peak emptying and filling velocities and LAA
emptying and filling VTIs were also significantly lower in
patients with spontaneous echo contrast as compared to
Table 3. Comparison of left atrial appendage function in patients with normal sinus rhythm - with and without left atrial
appendage clot
Parameters
LA diameter (mm)
2
Patient with clot
Patient without clot
(n=16)
(n=129)
p value
50.5±6.5
46.5±6.3
<0.05
LA area (cm )
33.9±10.6
27.9±6.2
<0.05
LAA maximum area (cm2)
6.4±2.8
5.4±1.9
NS
LAA ejection fraction (%)
31.2±13.2
41.3±11.5
<0.01
LAA emptying velocity (cm/s)
22.2±12.7
22.3±9.5
NS
LAA filling velocity (cm/s)
25.9±14.9
28.7±11.5
NS
LAA emptying VTI (cm)
1.8±1.1
2.1±1.2
NS
LAA filling VTI (cm)
1.8±1.3
2.6±1.3
NS
LAA: left atrial appendage; LA: left atrium; NSR: normal sinus rhythm; VTI: velocity time integral; NS: not significant
Table 4. Left atrial appendage function in relation to spontaneous echo contrast
Parameters
LA diameter (mm)
2
SEC present
SEC absent
(n=113)
(n=87)
p value
52.2±8.1
45.9 ±6.5
<0.0001
LA area (cm )
35.5±10.8
27.6±6.9
<0.0001
LAA maximum area (cm2)
6.5±2.7
5.5±1.9
<0.05
LAA ejection fraction (%)
30.3±16.2
40.3+11.8
<0.001
LAA emptying velocity (cm/s)
17.0±8.1
23.9±10.9
<0.0001
LAA filling velocity (cm/s)
21.7±11.5
29.4±12.7
<0.0001
LAA emptying VTI (cm)
1.7±1.0
2.3±1.4
<0.01
LAA filling VTI (cm)
1.9±1.3
2.7±1.3
<0.01
LA: left atrium; LAA: left atrial appendage; VTI: velocity time integral; SEC: spontaneous echo contrast
IHJ-757-04.p65
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Indian Heart J 2004; 56: 628–635
patients without spontaneous echo contrast. After
multivariate logistic regression analysis, AF (OR 5.33, 95%
CI 1.64-17.34, p=0.005) and LAA emptying velocity (OR
1.06, 95% CI 1.00 - 1.11, p = 0.02) were found to be
independently related to the presence of spontaneous echo
contrast in LAA.
In the subgroup of patients with NSR, peak filling
(25.9±11.6 v. 30.7±12.2 cm/s, p <0.005) and emptying
(19.3±7.8 v. 24.9±10.7 cm/s, p <0.05) velocities were
found significantly less in patients with spontaneous echo
contrast as compared to patients without spontaneous echo
contrast. Although LAA area (5.6±2.2 v. 5.4±1.9 cm2) was
larger and LAA ejection fraction (38.7±14.0 v. 41.2±11.3
%) was lower in patients with spontaneous echo contrast,
it did not reach statistical significance.
Discussion
Various studies have shown that LAA is the major site
of clot formation, especially in patients with mitral
stenosis.5-8, 20,21 It is assumed that the larger size and poor
contraction of LAA in mitral stenosis, which is reflected by
a decrease in ejection fraction, and reduced filling and
emptying velocities, leads to stasis of blood, which helps in
formation of clot. 23 Its long, narrow, tubular structure with
a narrow tip and muscular ridges inside the lumen also
make it more vulnerable for clot formation.26 After the
introduction of TEE, which enables the cardiac chambers
to be examined in more detail than with TTE, the interest
to evaluate the role of LAA contractile function has
increased and many reports on various heart diseases have
shown its correlation with presence of clot and
spontaneous echo contrast formation in LA or LAA.16-25
Among all the cardiovascular diseases, mitral stenosis had
the highest incidence of clot formation in LAA. However,
there are not enough studies properly evaluating LAA
function in a large number of patients with severe mitral
stenosis. In the present study we prospectively evaluated
LAA function in 200 consecutive patients with severe
mitral stenosis and compared them with controls. The
values of LAA ejection fraction and LAA flow velocities in
the controls were in agreement with previously published
reports.19,24,27
The incidence of rheumatic heart disease is still high in
the developing countries and the majority of the patients
who need anticoagulation were not receiving it because of
the delay in diagnosis, poor drug compliance and lack of
facilities to monitor the prothrombin time in the remote
areas. So we were able to collect a large number of patients
with severe mitral stenosis who were not on any anti-
IHJ-757-04.p65
633
Goswami et al. Predictors of Left Atrial Appendage Clot 633
coagulation despite being in AF and having past history of
embolic episodes.
Type of LAA flow pattern and its correlation with
LAA function and clot formation: In our study we
consistently found that LAA emptying velocity was
significantly less than LAA filling velocity in all the three
types of flow patterns, which was not reported in the
previous studies. In our control subset, both filling and
emptying velocities were identical. Previous studies had
either evaluated the emptying velocity or found both filling
and emptying velocities to be similar.16-25 This difference in
velocities in our study may be because of the fact that in
patients with severe mitral stenosis the elevated LA pressure
favors the filling waves while opposing the emptying waves
thus increasing the velocity of filling waves and decreasing
the velocity of emptying waves, which may not be true in
patients with non-rheumatic AF and other diseases with
normal LA pressure.
When patients were grouped according to the type of
LAA flow pattern, type II and type III had higher incidence
of clot and spontaneous echo contrast formation as
compared to type I. We consistently found that patients with
type II and type III flows had significantly larger LA and
LAA sizes, lower LAA ejection fraction, lower filling and
emptying velocities and VTIs as compared to those with
type I flow. There were few reports which studied patients
with mitral stenosis. 17,18,28 These studies had smaller
number of patients and did not evaluate all LAA function
parameters and flow patterns with respect to clot and
spontaneous echo contrast formation. Garcia-Fernandez
et al.21 studied 27 patients with rheumatic valvular heart
disease (not isolated mitral stenosis) and found that patients
with type III flow had highest incidence of LAA clot and
spontaneous echo contrast as compared to those with type
I and type II flows; however, they did not correlate the type
of flow pattern with other LAA function parameters. Porte
et al.18 reported that patients with mitral stenosis having
type II and type III flow patterns (n=37), had larger LA and
LAA sizes, lower LAA ejection fractions, lower filling and
emptying velocities as compared to those with type I flow
pattern, but they did not correlate the LAA flow patterns
with LAA clot and spontaneous echo contrast. In a different
subset of patients (various cardiovascular diseases, not
isolated mitral stenosis), Li et al.28 reported that patients
with type II and type III flow patterns had significantly
lower LAA ejection fraction, lower peak emptying velocity
and higher chance of spontaneous echo contrast and clot
formation as compared to those having type I flow.
LAA function and LAA clot: In the patients with severe
2/7/2005, 1:45 PM
Indian Heart J 2004; 56: 628–635
634 Goswami et al. Predictors of Left Atrial Appendage Clot
mitral stenosis we found significantly larger LAA size, lower
LAA ejection fraction and lower filling and emptying
velocities and VTIs as compared to controls. In the present
study LAA size was significantly more and ejection fraction
was significantly less in patients with clot in LAA. The LAA
emptying and filling velocities were also significantly less
in the patients with clot. Even in the subgroup of patients
with NSR, LAA ejection fraction was independently
correlated with clot formation in LAA. The higher incidence
of clot in patients with larger and poorly functioning LAA
with decreased ejection fraction, decreased filling and
emptying velocities favors the hypothesis of stasis of blood
in this chamber leading to increased incidence of clot
formation. After multivariate logistic regression analysis,
LAA ejection fraction along with AF was found to be
independently correlated with presence of clot. Pollick et
al.20 were the first to assess the LAA flow patterns and the
effect of LAA function on LAA clot formation in a different
subgroup of patients (for evaluation of prosthetic valve,
stroke and endocarditis). They found that patients with
sinus rhythm and LAA clot had increased LAA size as
compared to patients without clot. The LAA ejection
fraction and LAA velocities were also significantly less in
patients with clot as compared to patients without clot.
Patients with AF and clot or spontaneous echo contrast had
larger LAA area as compared to patients with AF but
without clot or spontaneous echo contrast.
LAA function and spontaneous echo contrast: The
presence of spontaneous echo contrast in LA has been
found to be strongly correlated with the development of
the clot and thromboembolization.10-16,29 The spontaneous
echo contrast may be confined to the LAA alone and when
distributed throughout the left atrium, it is usually more
dense in LAA thus lending credence to the hypothesis that
LAA function may be a useful indicator of the propensity
of spontaneous echo contrast. Many factors like AF, large
size of LA and poor LAA ejection fraction, type of flow
pattern and lower flow velocities were found to be predictors
for the development of spontaneous echo contrast in
patients with non-rheumatic and rheumatic heart
diseases.10-18 In our study, LAA was larger, LAA ejection
fraction and LAA emptying and filling velocities were lower
in patients with spontaneous echo contrast as compared
to patients without spontaneous echo contrast. Patients
with type II and type III flow patterns had significantly
higher prevalence of spontaneous echo contrast as
compared to type I. The presence of AF and lower LAA
emptying velocity were found to be the most important
variables for the development of spontaneous echo contrast
IHJ-757-04.p65
634
on multivariate logistic regression analysis. Even in patients
with NSR, LAA emptying velocity was found to be the only
predictor of spontaneous echo contrast formation. The
lower emptying velocity in patients with spontaneous echo
contrast further strengthens the role of blood stasis in the
formation of spontaneous echo contrast.30,31
Study limitations: The possibility of intermittent AF in
the patients with normal sinus rhythm could not be ruled
out, thus not strictly isolating the patients with true normal
sinus rhythm. This study only highlights the patients with
severe mitral stenosis; the patients with mild to moderate
mitral stenosis need to be further examined.
Conclusions: In the patients with severe mitral stenosis,
AF and LAA ejection fraction appear to be independent
predictors of clot and spontaneous echo contrast formation
in LAA. In a subgroup of patients with NSR, patients with
lower LAA ejection fraction (≤25%) had a higher risk of
LAA clot formation. In patients with mitral stenosis the
emptying velocity was consistently lower than filling
velocity and lower emptying velocity was the only
independent predictor for spontaneous echo contrast
formation in LAA. We suggest that these patients should
be anticoagulated for prevention of clot formation.
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2/7/2005, 1:45 PM
636 MulayArticle
et al. QT Dispersion in Acute Myocardial Infarction
Original
Indian Heart J 2004; 56: 636–641
QT Dispersion and Early Arrhythmic Risk in Acute
Myocardial Infarction
Dnyaneshwar V Mulay, Syed M Quadri
Department of Medicine, Government Medical College and Hospital, Aurangabad
Background: This study sought to find out QT dispersion in healthy individuals and patients of acute myocardial
infarction and to find correlation, if any, between QT dispersion and the incidence of ventricular arrhythmias
in acute myocardial infarction.
Methods and Results: QT dispersion was calculated from a 12-lead electrocardiogram in 100 patients of
acute myocardial infarction admitted in intensive coronary care unit and 100 age- and sex-matched healthy
individuals. In patients of acute myocardial infarction, QT dispersion was calculated on admission, 24 hours
after admission and at the time of discharge from intensive coronary care unit. Average QT dispersion in acute
myocardial infarction was found to be significantly higher on admission (76.4±18.3 ms), 24 hours after
admission (62.88±17.52 ms) and at the time of discharge from intensive coronary care unit (51.79±16.79
ms) than in healthy individuals (29.76±6.06 ms; p< 0.05). QT dispersion was found to be significantly increased
in patients of acute myocardial infarction with ventricular arrhythmias (82.06±16.86 ms) than in those without
(66.75±16.28 ms; p< 0.01). Patients of acute myocardial infarction with ventricular tachycardia or ventricular
fibrillation had significantly increased QT dispersion (96.25±15.97 ms) than those who had only ventricular
premature beats (80±15.04 ms; p<0.01). QT dispersion was found to be significantly greater in patients with
anterior wall acute myocardial infarction (79.80±18.19 ms) than in those with inferior wall acute myocardial
infarction (71.9±17. 48 ms; p<0.05). At the time of discharge from intensive coronary care unit no statistically
significant difference was found in QT dispersion in those who received thrombolysis (51.58±16.05 ms) and
those who did not (48.18±14.68 ms; p>0.05). QT dispersion was found to be significantly higher in those who
died (88.66±15.97 ms) than in those who survived (74.23±17.91 ms; p<0.05). QT dispersion was significantly
higher in ventricular arrhythmic deaths (97.14±17.04 ms) than those who had non-arrhythmiac deaths
(81.25±11.25 ms; p < 0.05).
Conclusions: Interlead QT variation and its measure as QT dispersion challenges our current approach to the
electrocardiographic assessment of arrhythmic risk. QT dispersion may provide a potentially simple, cheap,
non-invasive method of measuring underlying dispersion of ventricular excitability. (Indian Heart J 2004;
56: 636–641)
Key Words: QT dispersion, Acute myocardial infarction, Arrhythmia
I
dentification of patients at high risk of life-threatening
ventricular tachyarrhythmias represents one of the most
challenging issues in patient care, especially after acute
myocardial infarction (AMI). Experimental data have
demonstrated a strong link between the vulnerability of the
ventricular myocardium to serious tachyarrhythmias and
increased temporal dispersion of refractoriness.1,2
Day et al.3 first proposed that interlead variability of QT
intervals in 12-lead electrocardiogram–QT dispersion
Correspondence: Dr DV Mulay, Department of Medicine
Government Medical College and Hospital, Aurangabad 431001
IHJ-601-03.p65
636
(defined as the difference between maximum and minimum
QT interval duration) reflects dispersion of ventricular
recovery time, thus providing a conventional tool for clinical
studies. The increased QT dispersion results in prolongation
of the vulnerable period and thereby enhanced
susceptibility to ventricular arrhythmias. QT dispersion is
found to be increased in AMI and is associated with
increased susceptibility to ventricular arrhythmias.4-7 Since
patients are at increased risk of arrhythmic death after
myocardial infarction (MI), assessment of ventricular
depolarization could have important clinical implications.
It would be worthwhile to identify patients at risk by a
2/7/2005, 1:46 PM
Indian Heart J 2004; 56: 636–641
Mulay et al. QT Dispersion in Acute Myocardial Infarction 637
simple non-invasive and low cost procedure such as QT
dispersion, so that they could receive appropriate treatment.
Methods
One hundred patients of AMI admitted to intensive
coronary care unit (ICCU) and 100 age- and sex-matched
healthy individuals were included in the study. AMI was
diagnosed on the basis of history of typical chest pain
lasting for ≥30 min and unresponsive to nitrates and the
presence of ST segment elevation in the electrocardiogram
of 0.1 mv in ≥2 limb leads or 0.2 mv in ≥2 precordial leads.4
Simultaneous 12-lead electrocardiogram was recorded on
Schiller CS-200 diagnostic work station, at a paper speed
of 25 mm/s. QT dispersion was calculated in all the patients
of AMI as described by Van de Loo et al.4 on admission and
in those who survived, 24 hours after admission and at the
time of discharge from ICCU. QT dispersion was defined as
the difference between the maximum and minimum QT
interval measurements among all the measured 12 leads
on the standard electrocardiogram8 (QTd = QT max – QT min).
For analysis of QT dispersion, RR and QT intervals were
measured in as many of the 12 leads as possible. Each
measurement was taken as the mean value of 2 to 3
consecutive RR and QT intervals. Patients were excluded
from the study when the admission electrocardiogram
exhibited technical limitations for analysis of QT dispersion
(<8 evaluable leads) or patients were in atrial fibrillation
(AF) or flutter or had left or right bundle branch block.
Patients receiving long-term medications with drugs
influencing QT duration were also not considered for the
present study. Ventricular arrhythmias were analyzed and
its relationship to QT dispersion was observed.
QT dispersion among AMI: QT dispersion in AMI was
found to be significantly higher (76.4±18.30 ms) than in
normal individuals (29.76±6.06 ms, p<0.001). QT
dispersion in patients of AMI was found to be higher on
admission (76.4±18.30 ms) and was found to decrease
later in the course of disease (62.88±17.52 ms), 24 hours
after admission and at the time of discharge from ICCU after
an average stay of 4 days (51.79±16.79 ms). The difference
observed was statistically significant (p<0.05). The value
at the time of discharge (51.79±16.79 ms) was still higher
than normal (29.76±6.06 ms) and the difference was
statistically significant (p<0.05). QT dispersion was
significantly greater in patients with anterior wall AMI
(79.80±18.19 ms) than in those with inferior wall AMI
(71.9±17.48 ms; p<0.05).
QT dispersion and arrhythmias: QT dispersion was
significantly higher (82.06±16.86 ms) in 63 patients with
ventricular arrhythmias than 37 patients without
ventricular arrhythmias (66.75±16.28 ms; p<0.01). Fiftyfive patients had ventricular premature beats (VPBs), 2 had
ventricular tachycardia (VT) and 6 had ventricular
fibrillation (VF). QT dispersion was significantly higher in
patients with VT/VF (96.25±15.97 ms) than those who
had only VPBs (80±15.04, p<0.01).
QT dispersion and thrombolytic therapy: Out of 100
patients of AMI, 70 were thrombolyzed with streptokinase
and 30 were not. No statistically significant difference was
observed in QT dispersion in the two groups (51.58±16.05
ms v 48.18±14.68 ms; p>0.05) at the time of discharge
from ICCU.
Statistical analysis: Continuous variables were expressed
as mean±SD. Standard error of difference between two
means was used for comparing the differences. A value of
p<0.05 was considered statistically significant.
QT dispersion and prognosis: QT dispersion was found
to be significantly higher in those who died (88.66±15.97
ms) than in those who survived (74.23±17.91 ms;
p<0.05). QT dispersion was significantly higher in
arrhythmic deaths (97.14±17.04 ms) than in those who
had non-arrhythmiac deaths (81.25±11.25 ms; p<0.05).
Results
Discussion
Baseline characteristics: The present study consisted of
100 patients of AMI and an equal number of age- and sexmatched healthy individuals. The age of the healthy
individuals ranged from 25 to 90 years with a mean of
56.02±12.65 years. The age of patients with AMI ranged
from 25 to 91 years with a mean of 55.66±12.97 years.
There were 81 males and 19 females in each group. Out of
100 patients of AMI, 58 were having anterior wall AMI
and 42 had inferior wall AMI.
The present prospectively designed study aimed to examine
QT dispersion in 100 patients of AMI and an equal number
of age- and sex-matched healthy individuals.
IHJ-601-03.p65
637
QT dispersion in normal individuals: In normal
individuals a low QT dispersion was observed (29.76±6.06
ms). Similar values of QT dispersion have been reported
earlier.4,6,9-11 Somewhat higher values have been reported
in few other studies. 12-16 The results obtained by noninvasive assessment of QT dispersion from the surface
2/7/2005, 1:46 PM
Indian Heart J 2004; 56: 636–641
638 Mulay et al. QT Dispersion in Acute Myocardial Infarction
electrocardiogram are further substantiated by data
obtained from endocardial or epicardial catheter
mapping. 17 Using this method, several studies have
demonstrated regional differences in ventricular
repolarization times of 40 to 55 ms.18,19 Extensive body
surface mapping has also been used to assess disparities in
ventricular repolarization in healthy persons and has
revealed difference in QT duration of up to 60 ms.20 Taken
together these findings suggest that a range of QT dispersion
between 30 and 50 ms appears to represent the normal
limits of this parameter.
QT dispersion in AMI: QT dispersion in patients of
AMI ranged from 40 ms to 120 ms with an average of
76.4±18.30 ms which was significantly higher (p<0.001)
than in normal healthy individuals (29.76±6.06 ms). Our
results are similar to that reported in other studies.4,6,9-16
Patients with MI may have an inhomogenous ventricular
repolarization process. In the setting of AMI, the interplay
between ischemic living tissue and relatively depolarized
dying tissue would create a complex transition period
affecting QT interval dispersion. In early stage of AMI,
increase in QT dispersion would be primarily due to local
shortening of action potential. However, within few hours
prolongation of QT interval could become the dominant
feature governing QT dispersion.5
In AMI, QT dispersion was highest at the time of
admission (76.4±18.3 ms) and was found to decrease in
the course of time, 62.88±17.52 ms at 24 hours after
admission and 51.79±16.79 ms at the time of discharge.
The difference observed was statistically significant
(p<0.05). Similar observations have been made earlier.16,21
Glancy et al.22 measured QTc dispersion on days 1,2,3 and
6 in 17 patients with AMI. They found the maximal QTc
dispersion in the electrocardiogram taken on day 3.
However, in a large study of 316 consecutive patients,
Newby et al.23 could not find significant differences in QT
dispersion assessed at admission or after 2 and 3 days.
QT dispersion and site of infarct: QT dispersion was
significantly greater in anterior wall AMI (79.80±18.19
ms) than in inferior wall AMI (71.9±17.48 ms; p <0.05).
Similar observations have been made earlier.6,12-15 However,
Cowan et al.24 did not observe any significant difference in
QT dispersion with different territory MI.
QT dispersion and reperfusion therapy: In essence, the
determinants of increased QT dispersion during AMI are:
speed of reperfusion, patency of the infarct-related artery
(IRA) and location of AMI. Quick restoration of blood in
the IRA post-MI decreases QT dispersion. Studies have
IHJ-601-03.p65
638
shown that post-infarction patients with open arteries have
a lower mortality rate than patients with closed arteries.
Mortality rates as low as 2.5% have been reported in
patients with patent arteries compared with 15% in
patients with closed arteries.25 Mechanisms proposed to
account for the beneficial effects of early and late
reperfusion on mortality have been reviewed by Gersh and
Anderson.26
In the present study no statistically significant difference
was noted in QT dispersion at the time of discharge from
ICCU in those who received thrombolytic therapy
(51.58±16.05 ms) and those who did not (48.18±14.68
ms, p>0.05). Some previous studies12,15,16 also showed
significant reduction in QT dispersion while others reported
no change in QT dispersion after thrombolytic therapy.13,14
Moreno et al.12 studied 244 patients of AMI in whom they
assessed reperfusion and the IRA by coronary angiography
obtained 2.4±1 hours after start of thrombolysis. The degree
of QT dispersion significantly related to reperfusion status.
QT dispersion averaged 96±31 ms in patients with
permanently occluded IRA (TIMI grade 0), 88±25 ms in
patients with TIMI grade 1 reperfusion, 60±22 ms and
52±19 ms in patients with TIMI grade 2 or 3 reperfusion,
respectively (p=0.0001). Difference in QT dispersion postthrombolysis perhaps become clearer after a week or 10 days
of AMI as observed by Ciolli et al.14 and Parale et al.16 Endoh
et al.27 determined QT dispersion during the acute phase
(2.0±0.9 days) and during recovery period (14±6 days) after
AMI. They showed a significant reduction in the amount of
QT dispersion in patients with successful reperfusion therapy
whereas changes in QT dispersion were insignificant in
patients who did not undergo recanalization of the IRA.
Yunus et al.28 observed that mechanical relief of ischemia
by percutaneous transluminal coronary angioplasty (PTCA)
decreased QT dispersion (from 60±9 ms pre-PTCA to 29±18
ms post-PTCA) which returned back to pre-PTCA levels with
restenosis. Studies involving larger number and patients with
comparable QT dispersion values between the two groups
are needed to confirm the results.
QT dispersion, ventricular arrhythmias and mortality in AMI: In experimental investigations, electrodes
placed several millimeters apart with a small field of view
have measured regional disparities in repolarization.
Variation in ventricular recovery time is an important factor
in experimental tachyarrhythmias. The usual site of
abnormal dispersion from which arrhythmias occur is at
border zone of the infarcted area.29,30
In the present study QT dispersion was significantly
higher (p<0.01) in patients of AMI with ventricular
2/7/2005, 1:46 PM
Indian Heart J 2004; 56: 636–641
Mulay et al. QT Dispersion in Acute Myocardial Infarction 639
QT dispersion (ms)
arrhythmias (82.06±16.86 ms) than those without
(66.75±16.28 ms). QT dispersion was significantly higher
(p<0.01) in those with VT/VF (96.25±15.97 ms) than in
those with VPBs (80±15.04 ms) (Fig. 1). Similar
observations have been reported earlier.4,9,13-16,30 -32 It simply
illustrates the gradual increase in the heterogeneity of
ventricular recovery from normal subjects to patients with
uncomplicated MI to those with serious ventricular
arrhythmias. A graded relationship has been found
between the Lown grade (modified) of ventricular
arrhythmia on 24 hours monitoring and QT dispersion
88±17 ms in VT, 60±14 ms in monomorphic VPB and
43±8 ms in controls.33 These data therefore suggest that
QT dispersion increase in post-MI may relate to
arrhythmias, and is decreased by measures that relieve
ischemia or decrease arrhythmia incidence. This suggests
that QT dispersion should relate to prognosis in post-AMI
patients, and indeed that has been found in one major postMI study (AIREX study) wherein those with AMI who had
complicating heart failure, QT dispersion (measured on
day 5) was found to be an independent (albeit rather weak)
predictor of death.34 The study may not be applicable to all
post-MI patients as it looked at only those with heart failure
complicating AMI.
However, study by Leich et al. 35 did not reveal any
significant difference in QT dispersion in both the groups.
Healthy
subjects
AMI
AMI
without
VA
AMI
with
VA
AMI
with
VT/VF
Fig. 1. Box plot comparison of QT dispersion between healthy subjects and
patients of acute myocardial infarction (AMI) with and without ventricular
arrhythmias (VA) and patients of AMI with malignant ventricular arrhythmias
(VT/VF). The mean is represented by the centerline. Box on either side represents
1 standard deviation. The lines beyond the box represent the range of values.
IHJ-601-03.p65
639
Tomassoni et al.36 assessed QT dispersion in 543 consecutive patients enrolled in the TAMI-9 or the GUSTO-1
study; 43 of these patients suffered from VF. QT dispersion
was repeatedly measured in the electrocardiograms taken
at 2, 24 and 48 hours after the infarct. At all three time
intervals there were no significant differences in QT
dispersion between patients with and without primary VF.
Methodological problems in assessing QT dispersion may
atleast in part be responsible for the observed discrepancy
between the various studies addressing this question.
The major negative study suggesting that in unselected
post-MI patients there is no relation between QTc dispersion
and prognosis is provided by LIMIT II.37 QTc dispersion was
measured 2–3 days post-AMI (>2000 subjects followed for
1 day/5 years) and comparison of QTc dispersion made
between those 163 patients who died (112.1±44.4 ms) and
who survived (109.9±42.7 ms). No difference was found.
The authors concluded that QTc dispersion measured at
hospital discharge was not helpful in predicting mortality,
though perhaps a criticism of the study is the end point,
being over-all mortality rather than sudden cardiac death.
This study found that over time QTc dispersion did however
decrease more in those who survived than in those who
died (by 34 ms and 9 ms, respectively) (p=0.016),
suggesting that in long-term post-MI, a failure to shorten
the QTc dispersion might be associated with a poorer
prognosis. The failure of QT dispersion post-MI to predict
arrhythmic or total mortality has been confirmed recently
by Zabel et al.38 in a prospective study of 280 patients.
According to Davey39 also, it seems unlikely that there is a
powerful relationship between QT dispersion post-MI and
subsequent outlook. In the present study, QT dispersion at
admission was high in patients with AMI who died than
those who survived (88.66±15.97 v. 74.23±17.91 ms,
p<0.05). QT dispersion at admission was higher in patients
with AMI with arrhythmic death (97.14±17.04 ms) than
those who had non-arrhythmic death (81.25±11.25 ms,
p<0.05). Sredniawa et al.21 have made similar observation.
From the numerous studies conducted over last 5 to 8
years it is obvious that AMI is associated with changes in
the electrophysiological properties of the heart. By means
of assessing QT dispersion from the surface electocardiogram there is convincing evidence that in AMI, inhomogeneity in ventricular repolarization is augmented. Some
clinical observations also indicate that this increased disparity in repolarization is directly accompanied by the
occurrence of ventricular arrhythmias and may help
identify patients at high risk of sudden death. QT dispersion
challenges our current approaches to the electrocar-
2/7/2005, 1:46 PM
Indian Heart J 2004; 56: 636–641
640 Mulay et al. QT Dispersion in Acute Myocardial Infarction
diographic assessment of arrhythmic risk. It provides a
potentially simple, cheap, non-invasive method of
measuring underlying dispersion of recovery of ventricular
excitability. One should keep in mind, however, various
problems inherent in the current technology used to
determine QT dispersion from the surface electrocardiogram. It remains to be seen whether future
refinements in technology will enable clinicians to use
non-invasive assessment of disparity of ventricular
repolarization as any adjunctive means for improving the
care of patients with this common disease. The prognostic
importance of abnormalities in QT-heart rate relation
awaits the results, of large and long-term studies.
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642 TewariArticle
et al. Carotid Intima-Media Thickness and CAD
Original
Indian Heart J 2004; 56: 642–645
Association of Common Carotid Intima - Media Thickness
and Lipoprotein(a) with Coronary Artery Disease
Satyendra Tewari, Nitish Garg, Aditya Kapoor, Alkesh Jain, Uttam Singh, MM Godbole, Nakul Sinha
Departments of Cardiology, Biostatistics and Endocrinology,
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow
Background: Carotid artery intimal medial thickness is a simple, non-invasive and reproducible clinical tool to
evaluate atherosclerosis and predict coronary artery disease. Lipoprotein(a) levels are related to both atherogenesis
and thrombogenesis and may be a key link between lipid and coronary artery disease. This study evaluated the
association of carotid intimal medial thickness and lipoprotein(a) with coronary artery disease.
Methods and Results: We studied 185 randomly selected patients hospitalized for coronary angiogram in our
institute. There were 110 angiographically proven patients of coronary artery disease with mean age of 55.8±9
years (range 34-72 years) and 75 subjects with normal coronary artery anatomy with mean age of 54.8±8
years (range 34-68 years). The mean carotid intimal medial thickness of subjects with coronary artery disease
was significantly higher than in subjects without coronary artery disease (0.84±0.16 mm v. 0.65±0.15 mm,
p<0.001). The mean carotid intimal medial thicknesses in patients with triple vessel, double vessel and single
vessel disease were 0.96±0.12 mm, 0.84±0.11 mm and 0.78±0.13 mm, respectively (p=0.05). The mean
lipoprotein(a) of subjects with coronary artery disease was significantly higher than in subjects without coronary
artery disease (35.9±22.3 mg/dl v. 19.1±21.2 mg/dl, p<0.001). Mean lipoprotein(a) levels in subjects with
carotid intimal medial thickness <0.80 was 26.4±24.2 mg/dl and in subjects with carotid intimal medial
thickness ≥0.80 was 32.1±22.1 mg/dl (p=0.05).
Conclusions: There is a strong correlation between carotid and coronary atherosclerosis and carotid intimal
medial thickness is a good predictor of presence and extent of coronary artery disease. Lipoprotein(a) level is a
powerful independent risk factor for atherosclerosis. Carotid intimal medial thickness and lipoprotein(a) in conjoint
can predict coronary artery disease reliably. (Indian Heart J 2004; 56: 642–645)
Key Words: Carotid intimal medial thickness, Lipoprotein(a), Coronary artery disease
A
therosclerosis is a multifactorial and dynamic process.
One of its feature is the presence of fatty streaks along
the vessel wall leading to build-up of plaques on the wall of
arteries, which leads to reduction in caliber of vessels.
Coronary artery disease (CAD) in India is reaching alarming
and epidemic proportions.1,2
Lipoprotein(a) [Lp(a)] was first described 40 years ago
and adequate prospective data on its role in CAD have been
recently published. Numerous studies have shown that
Lp(a) is one of the major risk factors for CAD.3-6 Lp(a) acts
by two mechanisms. Firstly, Lp(a) inhibits the binding of
plasminogen to endothelial cells, fibrin and platelets by the
competitive inhibition and secondly, it regulates the
Correspondence: Dr Satyendra Tewari, Assistant Professor, Department
of Cardiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences
Rae Bareli Road, Lucknow 226014. e-mail: [email protected]
IHJ-557-03.p65
642
synthesis of plasminogen activator-1 by the endothelium.
Lp(a) levels may be related to both atherogenesis and
thrombogenesis and may be a key link between lipids and
thrombosis. Lp(a) is 10 times more atherogenic than lowdensity lipoprotein cholesterol (LDL-c). The levels of Lp(a)
have been found to be three times higher in Asian Indians.
Studies on Indians showed increased Lp(a) levels in patients
with atherosclerotic vascular disease as compared to
controls.7 A striking feature was that elevated Lp(a) leads to
CAD more prematurely and severely. Thus Lp(a) may be a
powerful risk factor for the development of premature CAD
in Indians.
The effects of Lp(a) get multiplied by abnormal lipid
profile. Lp(a) excess increases the risk of premature CAD 3to 100-fold, depending on the presence or absence of
concomitant risk factors.
2/7/2005, 1:46 PM
Indian Heart J 2004; 56: 642–645
Tewari et al.
Developments in technology have now made it possible
to assess the early sub-clinical changes of atherosclerosis,
which include endothelial dysfunction and gradual
thickening of intima. Pignoli et al.8 further developed the
technique of intimal medial thickness (IMT) measurements.
Today, progression of carotid IMT is considered as one of
best indices of future CAD risk. As atherosclerosis
predominantly affects the intimal layer of the artery,
technique, which facilitates the study of intima of the artery,
is the principle behind the IMT assessment.9 Carotid IMT
assessed non-invasively by B-mode ultrasound has been
recently shown to be the physiological marker for atherosclerosis.10 It is well known that there are marked ethnic
differences in the prevalence of CAD. Similarly, carotid IMT
also differs in different populations studied. Individuals from
countries with high prevalence rates of CAD tend to have
greater mean IMT.11 This prompted us to take up a study
on IMT as Indians have high rates of CAD. Carotid IMT has
been shown to be correlated with CAD in Indian subjects in
previous studies.12-14
Methods
Selection of patients: A total of 185 randomly selected
patients hospitalized for coronary angiogram in our
institution were studied. Patients without any angiographic
abnormality of coronary arteries were designated as control
subjects. CAD was defined as >50% diameter stenosis in
one or more arteries; 75 controls and 110 angiographically
proven CAD patients were included in the study.
Study design: Baseline biochemistry included lipid profile
and liver function tests to rule out any other systemic illness
or a secondary cause of dyslipidemia. Blood samples were
taken after a fasting period of 12 hours in all subjects. Total
cholesterol (TC), triglycerides (TG), high-density lipoproteins
(HDL), low-density lipoprotein (LDL) and very low density
lipoprotein (VLDL) were analyzed using enzymatic methods.
Lp(a) was measured by enzyme immunoassay (ELISA)
technique and the kit was manufactured by Biopool International, USA. The assay utilizes affinity-purified polyclonal
antibodies raised against Lp(a). Carotid IMT measurement was done in all the patients prior to angiogram.
Measurement of carotid IMT was done on B-mode using
7.5 MHz probe (HP 5000). Six well-defined arterial wall
segments were measured in each (right and left) carotid
system: the near wall and far wall of the proximal 1 cm of
the internal carotid artery, the near wall and far wall of the
carotid bifurcation, beginning at the tip of the flow divider,
and extending 1 cm below this point and near and far wall
IHJ-557-03.p65
643
Carotid Intima-Media Thickness and CAD 643
of the arterial segment, extending 1 cm below the tip of the
flow divider into common carotid artery, recorded in
videotape and two independent observers measured carotid
IMT.7 B-mode examination was performed twice by 2
sonographers on 2 different days, with at least a 2-week
interval between the first and the second scan. Each operator
selected and processed 10 images from each scan performed
by himself. Intraoperator and interoperator percent errors
in the evaluation of mean IMT were 2.5% (range: 0-0.54%)
and 5.9% (range: 0 - 8.31%), respectively. Coronary
angiography was performed by the percutaneous Judkins
technique and conventional views were taken to assess the
severity of the CAD.
Statistical analysis: Data were presented as mean±SD. The
statistical analyses were performed with the SPSS statistical
software package. Clinical parameters in patients with and
without CAD were compared by univariate analysis using
Student's t test for continuous variables and Chi-square
test for categorical variables. The variables that were
significantly different between CAD and non-CAD patients
in multiple univariate analysis were subjected to
multivariate analysis using a stepwise logistic regression.
For all analysis, a p value less than 0.05 was considered
significant.
Results
Coronary artery disease was documented in 110 patients
while 75 subjects had normal coronary anatomy. The mean
age (55.8±9 years v. 54.8±8 years) and gender distribution
were similar in the two groups as shown in Table 1. Smoking,
hypertension and diabetes mellitus were significantly more
common among those with CAD. Patients with CAD also
had significantly higher TC, TG, LDL and lower HDL levels.
Patients with CAD had higher mean carotid IMT
(0.84±0.16 mm v. 0.65±0.15 mm, p<0.001) and mean
Lp(a) levels (35.9±22.3 v. 19.1±21.2 mg/dl, p < 0.001).
CAD and carotid IMT were highly correlated with correlation
coefficient of 0.51 (p<0.01) (Fig. 1). The mean carotid IMT
of triple vessel, double vessel and single vessel diseases was
0.96±0.12 mm v. 0.84+0.11 mm v. 0.78±0.13 mm,
respectively (p=0.05 for all three groups among themselves)
(Table 2).
Of 185 subjects studied, 77 (41%) had Lp(a) > 30 mg/dl
while 108 (59%) had Lp(a) ≤30 mg/dl as shown in Table 3.
Of the 77 subjects with Lp(a) > 30 mg/dl, 59 (77%) had
CAD and of the 108 subjects with Lp(a) ≤30 mg/dl, 51
(47%) had CAD. In subjects with CAD, 54% (n=59) had
Lp(a) >30 mg/dl as compared to subjects with normal
2/7/2005, 1:46 PM
644 Tewari et al.
Table 1. Baseline characteristics of the study group
Parameters
CAD
(n=110)
Non-CAD
(n=75)
p value
Age (years)
Male
Female
Smoking
Hypertension
Diabetes mellitus
Family history of CAD
Body mass index (kg/m2)
Total cholesterol (mg/dl)
Triglycerides (mg/dl)
LDL-cholesterol (mg/dl)
HDL-cholesterol (mg/dl)
Total cholesterol/HDL
Lp(a) (mg/dl)
Carotid IMT (mm)
55.8±9
73 (66)
37 (34)
39 (35)
31 (28)
48 (43)
20 (18)
25.6 ±3.2
210±43
176±59
137±43
29±7
7.6±2.5
35.9±22.3
0.84±0.16
54.8±8.4
45 (60)
30 (40)
15 (20)
11 (15)
18 (24)
8 (11)
24.8±3.1
159±42
132±46
93±40
37±8
4.4±3.4
19.1±21.2
0.65±0.15
0.47
0.37
0.37
0.02
0.03
0.006
0.16
0.39
0.001
0.001
0.001
0.001
0.001
0.001
0.001
Values in parentheses are percentages
IMT: intimal medial thickness; CAD: coronary artery disease; Lp(a): lipoprotein(a);
LDL: low-density lipoprotein; HDL: high-density lipoprotein
Table 2. Severity of disease in different groups of carotid
IMT patients
Age in years
(mean)
52.79
54.87
56.58
57.74
Indian Heart J 2004; 56: 642–645
Carotid Intima-Media Thickness and CAD
Carotid IMT
(mm)
SVD
(n=28)
≤0.59
0.60 - 0.79
0.80 - 0.99
≥1.00
8
12
6
2
DVD
(n=47)
TVD
(n=35)
4
15
25
3
2
2
17
14
Values in parentheses are percentages, p value<0.01
IMT: intimal medial thickness; SVD: single vessel disease; DVD: double vessel disease;
TVD: triple vessel disease
were 39.2±19.5 mg/dl, 33.5±17.8 mg/dl and 31.8±16.8
mg/dl, respectively (p=0.05) while with normal coronary
anatomy, subjects had mean Lp(a) of 16.6 mg/dl. Taking
CAD as the dependent variable, on univariate analysis,
diabetes, smoking, TG, TC, LDL-c, HDL-cholesterol (HDL-c),
TC to HDL-c ratio, Lp(a) and carotid IMT were found to
have significant correlation with CAD. On multivariate
analysis we found that diabetes [odds ratio (OR) = 1.08,
95% CI=0.47-2.51, p<0.01], HDL-c (OR=0.87, 95%
CI=0.83-0.92, p<0.01) and carotid IMT (OR=1.068, 95%
CI=1.043-1.095) showed strong correlation with CAD as
shown in Table 4. These 3 predictors had overall predictive
power of 80% to predict disease, with 85% correct prediction
of patients with CAD and 72% correct prediction of controls.
Table 3. Distribution of patients in each group of Lp(a)
on the basis of carotid IMT
Carotid IMT
(mm)
Lp(a) ≤30 (n=108)
CAD
Non-CAD
(n=51)
(n=57)
Lp(a) >30 (n=77)
CAD
Non-CAD
(n=59)
(n=18)
≤0.59
0.60 - 0.79
0.80 - 0.99
≥1.00
8 (16)
14 (27)
23 (45)
6 (12)
6 (10)
15 (25)
25 (42)
13 (22)
29 (51)
14 (24)
13 (23)
1 (2)
7 (39)
6 (33)
4 (22)
1 (6)
Values in parentheses are percentages
IMT: intimal medial thickness; CAD: coronary artery disease; Lp(a): lipoprotein(a)
Table 4. Multivariate predictors of coronary artery disease
Predictors
Odds ratio
95% confidence
interval
p value
Diabetes mellitus
HDL-cholesterol
Carotid IMT
1.08
0.87
1.068
0.47-2.51
0.83-0.92
1.043-1.095
<0.01
<0.01
<0.01
< 0.59 mm
0.60-0.79 mm
0.80-0.99 mm
CAD: coronary artery disease; HDL: high-density lipoprotein; IMT:
intimal medial thickness
>1.0 mm
Fig. 1. Percentage of patients in CAD and non-CAD group on the basis of
carotid IMT.
CAD: coronary artery disease; IMT: intimal medial thickness
< 0.59 mm
0.60-0.79 mm
0.80-0.99 mm
coronary artery anatomy, where only 24% (n=18) had
Lp(a) >30 mg/dl (p<0.001). A significantly higher
proportion of subjects having Lp(a)> 30mg/dl had carotid
IMT>0.80 mm than patients having Lp(a)≤30 mg/dl (56%
v. 40%, p<0.001) (Fig. 2). Mean Lp (a) levels of subjects
with triple vessel, double vessel and single vessel diseases
IHJ-557-03.p65
644
>1.0 mm
Lp(a) < 30
Lp(a) > 30
Fig. 2. Percentage of patients in Lp(a) group on the basis of carotid IMT.
Lp(a): lipoprotein(a); IMT: intimal medial thickness
2/7/2005, 1:46 PM
Indian Heart J 2004; 56: 642–645
Tewari et al.
Carotid Intima-Media Thickness and CAD 645
Discussion
References
Carotid artery IMT is a simple, non-invasive and reproducible clinical tool to evaluate atherosclerosis and predict
CAD in humans. In our study, 61% of CAD patients had
carotid IMT > 0.8 mm while only 25% subjects with normal
coronary had carotid IMT > 0.80 mm, suggesting that the
patients with carotid IMT >0.80 mm had higher chances
of having CAD. The cardiovascular health study collaborative research group15 showed that in 4476 subjects
without clinical cardiovascular disease, who were followed
up for 6 years, the relative risk for myocardial infarction or
stroke for the quintile with highest IMT, as compared with
the lowest, was 3.87.
Carotid IMT showed a positive association with traditional risk factors like male sex, age, obesity, hypertension,
serum cholesterol, smoking and diabetes. In the Chennai
urban population study,14 the mean IMT among diabetic
subjects was higher (0.95±0.31 mm) than non-diabetic
subjects (0.074±0.14 mm) (p<0.001).
In our study, mean Lp(a) levels were higher in CAD
patients in comparison to those with normal coronaries. In
this study, patients with increased carotid IMT had
significantly higher level of Lp(a). Budde et al.16 showed
that Lp(a) levels correlate with number, severity and length
-extension of coronary lesions in patients undergoing
coronary angiography for clinically suspected coronary
atherosclerosis. In our study, patients with triple vessel
disease had highest level of Lp(a), while patients with single
vessel disease had least Lp(a) levels among CAD patients.
We found that Lp(a) had an association with CAD in
univariate analysis but not as an independent risk factor in
multivariate regression analysis.
1. Reddy KS, Yusuf S. Emerging epidemic of cardiovascular disease
in the developing countries. Circulation 1998; 97: 596–601
2. Yusuf S. Global burden of cardiovascular disease: a review of the
evidence of coronary artery disease in Indians: a global perspective.
Sethi KK (ed), 1998
3. Danesh J, Collins R, Peto R. Lipoprotein(a) and coronary heart
disease. Meta-analysis of prospective studies. Circulation 2000; 102:
1082–1085
4. Bostom AG, Cupples LA, Jenner JL, Ordovas JM, Seman LJ, Wilson
PW, et al. Elevated plasma lipoprotein(a) and coronary heart
disease in men aged 55 years and younger. A prospective study.
JAMA 1996; 276: 544–548
5. Bostom AG, Gagnon DR, Cupples LA, Wilson PW, Jenner JL,
Ordovas JM, et al. A prospective investigation of elevated
lipoprotein(a) detected by electrophoresis and cardiovascular
disease in women. The Framingham Heart Study. Circulation 1994;
90: 1688–1695
6. Nguyen TT, Ellefson RD, Hodge DO, Bailey KR, Kottke TE, AbuLebdeh HS. Predictive value of electrophoretically detected
lipoprotein(a) for coronary heart disease and cerebrovascular
disease in a community-based cohort of 9936 men and women.
Circulation 1997; 96: 1390–1397
7. Vashisht S, Wasir HS, Srivastava LM. Association between
incidence of lipoprotein(a) and coronary artery disease. Indian
Heart J 1992; 44: 223–226
8. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial
thickness of the arterial wall: a direct measurement with ultrasound
imaging. Circulation 1986; 74: 1399–1406
9. Grobbee DE, Bots ML. Carotid artery intima-media thickness as an
indicator of generalized atherosclerosis. J Intern Med 1994; 236:
567–573
10. Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu CR, Liu CH, et al. The
role of carotid arterial intima-media thickness in predicting
clinical coronary events. Ann Intern Med 1998; 128: 262–269
11. Ebrahim S, Papacosta O, Whincup P, Wannamethee G, Walker M,
Nicolaides AN, et al. Carotid plaque, intima-media thickness,
cardiovascular risk factors and prevalent cardiovascular disease
in men and women. The British Regional Heart Study. Stroke 1999;
30: 841–850
12. Jadhav UM, Kadam NN. Carotid intima-media thickness as an
independent predictor of coronary artery disease. Indian Heart J
2001; 53: 458–462
13. Mohan V, Premlatha G, Ravikumar R. Intimal medial thickness of
carotid arteries - an excellent measurement of atherosclerosis.
Asian J Diabet 1999; 1: 43–46
14. Mohan V, Ravikumar R, Shanthi Rani S, Deepa R. Intima-media
thickness of the carotid artery in South Indian diabetic and nondiabetic subjects. The Chennai Urban Population Study.
Diabetologia 2000; 43: 494–499
15. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson
SK Jr. Carotid-artery intima and media thickness as a risk factor
for myocardial infarction and stroke in older adults. N Engl J Med
1999; 340: 14–22
16. Budde T, Fechtrup C, Bosenberg E, Vielhauer C, Enbergs A, Schulte
H, et al. Plasma Lp(a) levels correlate with number, severity, and
length - extension of coronary lesions in male patients undergoing
coronary arteriography for clinically suspected coronary
atherosclerosis. Arterioscler Thromb 1994; 14: 1730–1736
Limitations: The limitation of our study was that it was
not a prospective study but a cross sectional observational
study. Our subjects with CAD belong to a high risk subset
with more prevalence of conventional risk factors and
dyslipidemia.
Conclusions: Carotid IMT is a simple, non-invasive and
reproducible clinical tool to evaluate atherosclerosis. There
was a strong correlation between carotid atherosclerosis
and coronary atherosclerosis and carotid IMT is a good
predictor of presence and extent of CAD, hence it can be
used as a marker in the prediction of pre-clinical
atherosclerosis and CAD. Measurements of carotid IMT and
Lp(a) can help identify high risk individuals for CAD.
IHJ-557-03.p65
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2/7/2005, 1:46 PM
646 GuptaArticle
et al. Jaipur Heart Watch-3
Original
Indian Heart J 2004; 56: 646–652
High Prevalence of Multiple Coronary Risk Factors in
Punjabi Bhatia Community: Jaipur Heart Watch-3
Rajeev Gupta, Mukesh Sarna, Jyoti Thanvi, Priyanka Rastogi, Vijay Kaul, VP Gupta
Monilek Hospital and Research Centre and Departments of Statistics and Home Science, University of Rajasthan, Jaipur
Background: Studies among emigrant Indian populations have shown a high prevalence of obesity and many
coronary risk factors in Bhatia community. To determine the prevalence of risk factors in this community within
India we performed an epidemiological study.
Methods and Results: An ethnic-group sample survey to determine prevalence of cardiovascular risk factors
was performed using community registers for enrollment. Methodology used was similar to Jaipur Heart Watch
studies performed in 1995 and 2002. We invited 600 randomly selected subjects listed in Punjabi Bhatia
community registers and could examine 458 (76.7%) persons (men 226, women 232). Evaluation for coronary
risk factors, anthropometric measurements, blood pressure, electrocardiogram, fasting blood glucose and serum
lipids was performed using standard definitions. Mean age was 43.2±14.6 years in men and 44.7±15.3 years
in women. In both men and women there was a high prevalence of family history of coronary heart disease in
45 (19.9%) and 50 (21.6%), family history of diabetes in 96 (42.5%) and 77 (33.2%), sedentary habits in 82
(36.3%) and 73 (31.5%), smoking or tobacco use in 59 (26.1%) and 4 (1.7%), overweight or obesity (body
mass index ≥25 kg/m2) in 123 (54.0%) and 161 (69.4%), severe obesity (body mass index >30 kg/m2) in 47
(20.8%) and 75 (32.3%), truncal obesity (waist-hip ratio: men >0.9, women >0.8) in 175 (77.4%) and 186
(80.2%), increased waist (waist size: men >102 cm, women >88 cm) in 78 (34.5%) and 129 (55.6%),
hypertension (blood pressure ≥140/90 mmHg) in 116 (51.3%) and 120 (51.3%), diabetes in 40 (17.7%) and
33 (14.2%), hypercholesterolemia (total cholesterol ≥200 mg/dl) in 75 (33.2%) and 67 (28.9%), high
triglycerides in 55 (24.3%) and 34 (14.7%), low high-density lipoprotein cholesterol in 169 (74.8%) and 155
(66.8%), and the metabolic syndrome (defined by American National Cholesterol Education Program) in 84
(36.2%) and 111 (47.8%) respectively. Body mass index correlated significantly with (age-adjusted r2 value men, women) waist diameter (0.52, 0.12), waist-hip ratio (0.21, 0.10), truncal obesity (0.54, 0.60), systolic
blood pressure (0.19, 0.16), diastolic blood pressure (0.12, 0.16), hypertension (0.19, 0.31), and metabolic
syndrome (0.28, 0.44) (p <0.05). There was a significant linear relationship of body mass index with the
prevalence of hypertension, hypercholesterolemia, diabetes (women), and the metabolic syndrome (χ2 for trend
p<0.05). Prevalence of these risk factors was the lowest in subjects with body mass index <20 kg/m2. A
multivariate ordinal logistic regression analysis revealed that obesity was independently associated with multiple
risk factors characterized by metabolic syndrome after adjustment for age, hypertension, and diabetes in both
men (odds ratio 2.45, 95% confidence intervals 1.69, 3.57) as well as in women (odds ratio 2.93, 95% confidence
intervals 1.86, 4.61) (p<0.01).
Conclusions: There is a high prevalence of obesity, abdominal obesity, hypertension, diabetes, lipid abnormalities
and the metabolic syndrome in this community that is significantly greater than reported studies in Jaipur and
urban populations elsewhere in India. Obesity correlates strongly with multiple coronary risk factors of which
it is an important determinant. (Indian Heart J 2004; 56: 646–652)
Key Words: Obesity, Coronary risk factors, Epidemiology
Correspondence: Dr Rajeev Gupta, Department of Medicine
Monilek Hospital and Research Centre, Jawahar Nagar, Jaipur 302004
e-mail: [email protected]
IHJ-736-04.p65
646
V
arious studies have reported that there is difference in
prevalence of coronary risk factors and coronary heart
disease (CHD) among emigrant Indian sub-communities.
2/7/2005, 1:47 PM
Indian Heart J 2004; 56: 646–652
Ramaiya et al.1,2 reported that coronary risk factors were
more prevalent in Patel (Gujarati) and Bhatia (Punjabi)
3
communities living in Tanzania. Bhopal et al. reported a
greater prevalence of risk factors among Bangladeshi
emigrants as compared to Pakistani and Indian subjects in
UK. In India it has been reported that Gujaratis living in
Delhi have a greater coronary risk factor profile as
compared to local communities and there was no difference
in risk factors among Hindu and Muslim communities.4,5
Gupta et al.6 did not report any significant differences in
coronary risk factors in Hindu and Muslim communities
in Jaipur. A higher prevalence of hypertension in Parsi
community in Mumbai has been reported.7 Studies on
migrants have found a greater prevalence of coronary risk
factors among the North Indian Bhatia community in
Tanzania and Britain.1,2 The city of Jaipur has a large
numbers of subjects of this community. Therefore to
evaluate the prevalence of various coronary risk factors in
randomly selected sample of Bhatia community in Jaipur
and using the methodology of previous Jaipur Heart Watch
(JHW) studies,8,9 we performed an epidemiological study,
the Jaipur Heart Watch-3.
Methods
The study was approved by the institution ethics committee.
A proforma was prepared that incorporated information
regarding demographic, anthropometric and clinical
parameters. 8,9 This included the family history of
hypertension and CHD, details of major cardiovascular risk
factors such as smoking, amount of physical activity,
diabetes and hypertension. Physical examination was
undertaken for measurement of height, weight, waist-hip
ratio (WHR) and blood pressure (BP). Height was measured
in centimetres and weight in kilograms using calibrated
spring-balance. Standing waist girth was measured at the
level of umbilicus with person breathing quietly and
standing. The hip girth was measured at inter-trochanteric
level according to the World Health Organization (WHO)
guidelines.10 Sitting blood pressure was measured using
standard mercury manometer. At least two readings at 5
min intervals as per WHO guidelines were recorded.11 If a
high blood pressure (≥140/90) was noted, a third reading
was taken after 30 min. The lowest of the three readings
was taken as blood pressure. Fasting blood sample was
obtained from all the individuals for estimation of glucose,
total cholesterol (TC), high-density lipoprotein cholesterol
(HDL-c), low- density lipoprotein (LDL) chlesterol (LDL-c)
and triglycerides (TG) using the previously standardized
techniques.12
IHJ-736-04.p65
647
Gupta et al.
Jaipur Heart Watch-3 647
This study was designed to investigate the people of a
single community in Jaipur (JHW-3) unlike the previously
reported population-based JHW-1 in 19958 and JHW-2 in
2002. 9 We studied Bhatia populations in colonies of
Jawahar Nagar, Janta Colony and Adarsh Nagar. Details of
the Bhatia subjects in these locations were available from
the Bhatia community register maintained at Bhatia
Bhawan, Jaipur. The target subjects were adults ≥20 years
and from the register we randomly selected 600 subjects
(300 men, 300 women). The study was preceded by
meetings with local leaders who cooperated in identifying
and ensuring participation of selected subjects.
Diagnostic criteria: Smokers in India consume tobacco
in various forms - rolled tobacco leaves (bidi), Indian pipe
(chillum, hookah), cigarettes and tobacco-chewing, and
more than one form is used by many making it difficult to
accurately measure the amount of tobacco consumed.
Therefore, users of all types of tobacco products and present
and past smokers have been included in smoker category.
The diagnostic criteria for tobacco use as well as other
coronary risk factors adopted were in accordance with
American College of Cardiology clinical data standards.13
Physical activity was measured by asking about both workrelated and leisure-time activities as used in the previous
study.9 Hypertension was diagnosed when systolic BP was
≥ 140 mmHg and diastolic BP was ≥ 90 mmHg or a person
was a known hypertensive. Body mass index (BMI) was
calculated as weight in kg divided by square of height
in metres and overweight and obesity defined as BMI ≥25
kg/m2. Truncal obesity was diagnosed when waist-hip ratio
(WHR) was >0.9 in males and >0.8 in females while
abdominal obesity was diagnosed when waist size was
>102 cm in men and >88 cm in women as per the US
National Cholesterol Education Program (NCEP)
guidelines.14 Dyslipidemia was defined by the presence of
high TC (≥200 mg/dl), high LDL-c (≥130 mg/dl), low HDLc (<40 mg/dl) or high TG (≥150 mg/dl) according to NCEP
guidelines. 14 Metabolic syndrome was also diagnosed
according to NCEP guidelines when any three of the five
identifying risk factors [abdominal obesity, fasting glucose
>110 mg/dl or diabetes, BP ≥130/90 mmHg, low HDL-c
(men <40 mg/dl, women <50 mg/dl) or high TG (≥150
mg/dl)] were present.14
Statistical analysis: Continuous variables are reported as
mean ± 1 SD. The prevalence rates are given in percentage.
Age-related trends have been examined by Mantel-Haenzel
χ2 for trend. To determine correlation of BMI with multiple
coronary risk factors a Pearson correlation analysis was
first performed and as age is an important determinant of
2/7/2005, 1:47 PM
648 Gupta et al.
Indian Heart J 2004; 56: 646–652
Jaipur Heart Watch-3
BMI, partial correlation coefficients (r2) were calculated
after age-adjustment. Continuous variables have been
compared using t test and categorical variables by χ2 test.
BMI levels were divided into different groups with BMI <20,
20.0 to 22.9, 23.0 to 24.9, 25.0 to 29.9 and ≥30 kg/m2
according to WHO guidelines.10
Prevalence of coronary risk factors in different BMI
groups was determined and trends examined using MantelHaenzel χ2 for trend and least-squares regression method.
To determine influence of obesity on prevalence of multiple
metabolic abnormalities in men and women we performed
a conditional multivariate logistic regression analysis using
a commercially available statistical programme (SPSS
Version10.0, SPSS Inc, Chicago, USA). The dependent
variable was presence or absence of metabolic syndrome
and independent variables were obesity, age, diabetes,
hypertension and truncal obesity. Age was included as a
continuous variable while other variables were
dichotomized. p values <0.05 were considered significant.
Direct method of age-adjustment was used to compare
prevalence rates of various risk factors in the present study
with the previous Jaipur Heart Watch studies.
Results
We could evaluate 458 subjects (226 men and 232 women)
out of the targeted 600 (response rate 76.7%). The mean
age of men was 43.2±14.6 years and in women it was
44.7±15.3 years (p= NS). Prevalence of risk factors in the
study group is described in Table 1. There was a high
Table 1. Prevalence of major coronary risk factors
Risk factors
CHD in 1° relatives
Family history of diabetes
Known CHD
Sedentary habits (work or leisure)
Smoking/tobacco use
Regular alcohol use
Obesity, BMI ≥25 kg/m2
Severe obesity, BMI ≥30 kg/m2
Truncal obesity, cm
(waist:hip, men >0.9, women >0.8)
Abdominal obesity, cm
(men >102 cm, women >88 cm)
Hypertension
(known or BP ≥140/90 mmHg)
Diabetes (known or FBG ≥126 mg/dl)
High total cholesterol ≥200 mg/dl
LDL cholesterol ≥130 mg/dl
Triglycerides ≥150 mg/dl
Low HDL cholesterol <40 mg/dl
Metabolic syndrome
Men
(n=226)
Women
(n=232)
Total
(n=458)
45 (19.9)
96 (42.5)
7 (3.1)
82 (36.3)
59 (26.1)
35 (15.5)
123 (54.0)
47 (20.8)
50 (21.6)
77 (33.2)
11 (4.7)
73 (31.5)
4 (1.7)
2 (0.9)
161 (69.4)
75 (32.3)
95 (20.7)
173 (37.8)
18 (3.9)
155 (33.8)
63 (13.7)
37 (8.1)
284 (62.0)
122 (26.6)
175 (77.4)
186 (80.2)
361 (78.8)
78 (34.5)
129 (55.6)
207 (45.2)
116 (51.3)
40 (17.7)
75 (33.2)
86 (38.1)
55 (24.3)
169 (74.8)
84 (36.2)
120 (51.7)
33 (14.2)
67 (28.9)
81 (34.9)
34 (14.7)
155 (66.8)
111 (47.8)
236 (51.5)
77 (16.8)
142 (31.0)
167 (36.5)
89 (19.4)
324 (70.7)
195 (42.6)
Values in parentheses are percentage
CHD: coronary heart disease; BMI: body mass index; BP: blood pressure; FBG: fasting blood glucose;
LDL: low-density lipoprotein; HDL: high-density lipoprotein
IHJ-736-04.p65
648
prevalence of family history of CHD and diabetes in the
study subjects. A high prevalence of obesity, abdominal
obesity, hypertension, diabetes, lipid abnormalities and
multiple metabolic abnormalities (the metabolic syndrome)
was also seen in both men and women.
Age-specific prevalence of risk factors is outlined in
Table 2. In men, increasing age was associated with a
significantly increasing trend in prevalence of severe
obesity (BMI ≥30 kg/m2), truncal obesity, waist (abdominal)
obesity, hypertension, diabetes, metabolic syndrome and
high cholesterol levels. In women, with increasing age there
was a significant increase of obesity, severe obesity,
increased waist circumference, hypertension, diabetes,
metabolic syndrome and lipid abnormalities (MantelHaenzel χ2 for trend, p <0.05).
In men the BMI in age groups 20-29, 30-39, 40-49, 5059 and ≥ 60 years was 25.6±11.1, 26.6±5.6, 27.2±4.3,
27.8±4.5 and 24.1±4.6 kg/m2, respectively (ANOVA F=
2.29, r2=0.03, eta2=0.04, p=0.061). In women it was
23.5±4.7, 26.9±4.9, 28.7±4.9, 29.9±6.2 and 30.1±6.1
kg/m2 respectively (ANOVA F= 10.46, r2= 0.14, eta2= 0.18,
p<0.00001). BMI correlated (r value - men, women)
significantly with waist diameter (0.67, 0.14), systolic BP
(0.26, 0.26), diastolic BP (0.20, 0.19), fasting glucose
(0.12, 0.15), TC (0.13, 0.27) and TG (0.14, 0.15) (p
<0.05). As age was a major confounding factor, we
calculated partial correlation coefficients (r2) for BMI with
various factors after adjustment for age. A significant
correlation of BMI was observed in men and women with
waist diameter (0.54, 0.12), WHR (0.21, 0.10), truncal
obesity (0.54, 0.60), systolic BP (0.19, 0.16), diastolic BP
(0.12, 0.16), prevalence of hypertension (0.19, 0.31), and
metabolic syndrome (0.28, 0.44) (p<0.05).
Trend analysis (χ2 for trend, Table 3) demonstrated
that there was a significant linear relationship of BMI
with the presence of hypertension (p<0.0001),
hypercholesterolemia (p=0.039), hypertriglyceridemia
(p=0.003) and the metabolic syndrome (p<0.0001) in
men. In women a significant correlation was observed
with hypertension (p<0.0001), diabetes (p=0.006),
hypercholesterolemia (p=0.01), low HDL-c (p=0.07) and
the metabolic syndrome (p<0.0001). The lowest prevalence
of these risk factors is observed at BMI <20 kg/m2 and a
marked increase is seen at BMI ≥25 kg/m 2 (Fig. 1).
Multivariate ordinal logistic regression analysis confirmed
that obesity was an independent determinant of multiple
metabolic abnormalities as shown by metabolic syndrome.
Results of conditional logistic regression with metabolic
syndrome as dependent variable and successive addition
of independent variables of obesity, age, hypertension,
2/7/2005, 1:47 PM
≥
Indian Heart J 2004; 56: 646–652
Gupta et al.
Jaipur Heart Watch-3 649
Table 2. Age-specific prevalence of coronary risk factors
Age 20-29
Age 30-39
Age 40-49
Age 50-59
Age ≥60
Total
Number
Smoking/ tobacco
Physical inactivity
Hypertension
Obesity (BMI ≥25 kg/m2)
Severe obesity (BMI ≥30 kg/m2)
Truncal obesity (WHR >0.9)
Abdominal obesity >102 cm
Diabetes (history or FBG≥126 mg/dl)
High cholesterol (≥200 mg/dl)
High LDL (≥130 mg/dl)
Low HDL (<40 mg/dl)
High TG (≥150 mg/dl)
Metabolic syndrome
42
8 (19.0)
20 (47.6)
9 (21.4)
14 (33.3)
5 (11.9)
24 (57.1)
4 (9.5)
1 (2.3)
6 (14.3)
8 (19.0)
28 (66.7)
7 (16.7)
7 (16.7)
45
15 (33.3)
18 (40.0)
19 (42.2)
24 (53.3)
11 (24.4)
34 (75.5)
13 (28.9)
1 (2.2)
15 (33.3)
20 (44.4)
35 (77.7)
11 (24.4)
12 (26.7)
Men (n=226)
58
17 (29.3)
22 (37.9)
28 (48.3)
38 (65.5)
18 (31.0)
49 (84.5)
25 (48.1)
9 (15.5)
24 (41.4)
24 (41.4)
45 (77.6)
14 (24.1)
21 (36.2)
34
10 (29.4)
10 (29.4)
27 (79.4)
28 (82.3)
11 (32.4)
29 (85.3)
21 (61.8)
12 (35.3)
16 (47.1)
18 (52.9)
27 (79.4)
15 (55.1)
23 (67.6)
47
9 (19.1)
12 (25.5)
33 (70.2)
19 (40.4)
3 (6.4)
39 (82.9)
15 (31.9)
17 (36.2)
14 (29.8)
16 (34.0)
34 (72.0)
8 (17.0)
21 (44.7)
226
59 (26.1)
82 (36.3)
116 (51.3)*
123 (54.0)*
47 (20.8)*
175 (77.4)*
78 (34.5)*
40 (17.7)*
75 (33.2)*
86 (38.1)
169 (74.8)
55 (24.3)
84 (37.2)*
Number
Smoking/ tobacco
Physical inactivity
Hypertension
Obesity (BMI ≥25 kg/m2)
Severe obesity (BMI ≥30 kg/m2)
Truncal obesity (WHR >0.8)
Abdominal obesity >88 cm
Diabetes (history or FBG ≥126 mg/dl)
High cholesterol (≥200 mg/dl)
High LDL (≥130 mg/dl)
Low HDL (<40 mg/dl)
High TG (≥150 mg/dl)
Metabolic syndrome
40
16 (40.0)
3 (7.5)
14 (35.0)
5 (12.5)
28 (70.0)
11 (27.5)
5 (12.5)
6 (15.0)
18 (45.0)
4 (10.0)
4 (10.0)
62
2 (3.2)
20 (32.2)
18 (29.0)
46 (74.2)
18 (29.0)
52 (83.9)
33 (53.2)
1 (1.6)
14 (22.6)
20 (32.2)
42 (67.7)
6 (9.7)
19 (42.2)
Women (n=232)
49
1 (2.0)
14 (28.6)
33 (67.3)
39 (79.6)
16 (32.7)
42 (85.7)
29 (59.2)
6 (12.2)
17 (34.7)
18 (36.7)
35 (71.4)
9 (18.4)
29 (50.0)
44
1 (2.3)
12 (27.3)
32 (72.7)
34 (77.3)
18 (40.9)
37 (84.1)
32 (72.7)
12 (27.3)
15 (34.1)
18 (40.9)
30 (68.2)
7 (15.9)
30 (88.2)
37
11 (29.7)
34 (91.9)
29 (78.4)
19 (51.4)
27 (72.9)
24 (64.9)
14 (37.8)
16 (42.2)
19 (51.4)
30 (81.1)
8 (21.6)
29 (61.7)
232
4 (1.7)
73 (31.5)
120 (51.3)*
161 (69.4)*
75 (32.3)*
186 (80.2)
129 (55.6)*
33 (14.2)*
67 (28.9)*
81 (34.9)*
155 (66.8)*
34 (14.7)*
111 (47.8)*
Risk Factor
Values in parentheses are percentage. BMI: body mass index; BP: blood pressure; FBG: fasting blood glucose; LDL: low-density lipoprotein; HDL: high-density lipoprotein;
TG: triglycerides; * χ2 for trend p<0.05
diabetes and truncal obesity in the equation reveal that
obesity is an independent determinant as shown in
Table 4. Age-adjusted odds ratio (95% confidence interval)
for metabolic syndrome dependent on obesity after adjustment for age, hypertension and diabetes was 2.45 (1.69,
3.57) for men and in women it was 2.93 (1.86, 4.61)
(p<0.001). The significance of obesity decreases when
truncal obesity is added to the equation suggesting that
both of these are significant interdependent determinants.
We compared age-adjusted prevalence of major
coronary risk factors in the present study with previous
studies performed by the same group of investigators using
the same methodology (Table 5). As compared to JHW-1
study done in 1993-1994 and JHW-2 study done in 19992001, the present study performed in 2002-2003 shows
that many risk factors are greater in the Bhatia community.
Prevalence of obesity, truncal obesity, hypertension, high
LDL-c, low HDL-c, hypertriglyceridemia and the metabolic
syndrome is significantly greater as compared to previous
studies. The prevalence of smoking is significantly lower
IHJ-736-04.p65
649
and that of self-reported leisure-time physical activity
significantly greater in the present study group.
Discussion
The present study shows that there is a high prevalence of
obesity, abdominal obesity, hypertension, diabetes, lipid
abnormalities and the metabolic syndrome in the North
Indian Punjabi Bhatia community. The prevalence of these
risk factors is significantly greater than reported in studies
from Jaipur and urban population elsewhere in India. BMI
and obesity correlate strongly with multiple coronary risk
factors, and are major determinants of these risk factors.
Ramaiya et al.1 studied emigrant Indian populations in
Tanzania for prevalence of cardiovascular risk factors. They
reported that obesity, hypertension, glucose intolerance and
diabetes and lipid abnormalities were significantly greater
in Bhatia and Patel Hindu communities as compared to
other South Asian groups. Age-adjusted prevalence of
impaired glucose tolerance (27.2%), diabetes (14.3%), stage
2/7/2005, 1:47 PM
650 Gupta et al.
Indian Heart J 2004; 56: 646–652
Jaipur Heart Watch-3
Table 3. Body-mass index quintiles and prevalence of various risk factors
Risk factors
BMI groups
(kg/m2)
Numbers
Hypertension
Diabetes
High TC
(≥200 mg/dl)
High
triglycerides
(≥150 mg/dl)
Low HDL
cholesterol
(<40 mg/dl)
Metabolic
syndrome
Men (n=226)
≤ 20.0
20.0-22.9
23.0-24.9
25.0-29.9
≥ 30.0
χ2 trend (p value)
27
25
51
75
48
8 (29.6)
4 (16.0)
23 (45.1)
50 (66.7)
17 (35.4)
22.04, <0.0001
3 (11.1)
8 (32.0)
5 (9.8)
18 (24.0)
6 (12.5)
0.01, 0.969
3 (11.1)
9 (36.0)
17 (33.3)
28 (37.3)
18 (37.5)
4.22, 0.039
1 (3.7)
2 (8.0)
12 (23.5)
29 (38.7)
11 (22.9)
9.03, 0.003
21 (77.8)
3 (11.1)
17 (68.0)
4 (16.0)
41 (80.4)
8 (15.7)
55 (73.3)
39 (52.0)
35 (72.9)
30 (62.5)
0.11, 0.736 35.32, <0.0001
≤ 20.0
20.0-22.9
23.0-24.9
25.0-29.9
≥ 30.0
χ2 trend (p value)
16
31
23
86
76
1 (6.3)
9 (29.3)
9 (39.1)
44 (51.2)
57 (75.0)
36.04, <0.0001
3 (9.7)
3 (13.0)
8 (9.3)
19 (25.0)
7.58, 0.006
Women (n=232)
5 (16.1)
7 (30.4)
26 (30.2)
29 (38.2)
11.12, 0.001
1 (6.3)
6 (19.4)
3 (13.0)
12 (13.9)
12 (30.3)
0.13, 0.724
9 (56.3)
13 (41.9)
4 (12.9)
16 (69.6)
7 (30.4)
62 (72.1)
42 (48.8)
55 (72.4)
58 (76.3)
7.38, 0.007 53.82, <0.0001
Values in parentheses are percentage. TC: total cholesterol; HDL: high-density lipoprotein; BMI: body mass index
II hypertension (19.4%), overweight (22.7%) and mild
hypercholesterolemia (26.8%) were the highest in Bhatia
community as compared to six other groups. In a study
comparing cardiovascular risk factors and diabetes in
Bhatia community living in Tanzania and in the UK it was
reported that prevalence of known diabetes, hypertriglyceridemia, hypertension and obesity were not different
in Tanzanian and UK Bhatias but the prevalence of
impaired glucose tolerance, diabetes, hypercholesterolemia
and smoking was significantly higher and sedentary
lifestyle more common in subjects in Africa.2 Williams
et al.15 reported on non-biochemical cardiovascular risk
factors in different South Asian groups in Glasgow, UK.
South Asians, especially the British Punjabi subjects had a
lower prevalence of smoking but there was a greater
prevalence of sedentary habits, higher diastolic blood
pressure, higher BMI, insulin resistance, stress, and
socioeconomic deprivation. Cappuccio et al.16 reported
prevalence of cardiovascular risk factors in different ethnic
groups in South London. As compared to subjects of
Caucasian and African descent, South Asians had a twoto three-fold excess of hypertension and diabetes and an
inferior control of hypertension. It was concluded that the
excess of CHD mortality among South Asians may be due
to the higher prevalence of non-metabolic as well as
metabolic risk factors. Greater prevalence of coronary risk
factors in the Punjabi Bhatia community in Jaipur, when
compared to the previous studies, is in agreement with
these observations.
In India there have been only a few community-specific
IHJ-736-04.p65
650
studies of risk factors. Chopra and Chopra 17 studied
prevalence of high blood pressure among different groups
in India in early 1940s. They reported higher mean systolic
blood pressure in North Indians, especially those living in
Punjab, as compared to the South Indian subjects.
Malhotra18 studied railway workers for cardiovascular risk
factors in mid 1960s and found that there was a difference
in prevalence of CHD as well as risk factors in different parts
of India. He reported a higher prevalence of risk factors in
North Indian workers as compared to the South Indians.
Gopinath et al.5 reported prevalence of risk factors in
multiple ethnic groups in Delhi. The prevalence rates of
CHD were the highest in Sikhs, lowest in Muslims and
identical in Hindus and Christians. Sikhs also had the
highest prevalence of obesity, hypertension and diabetes.
The present study also shows that the Punjabi Bhatia
community has a very high prevalence of obesity and
multiple coronary risk factors as compared to Jaipur general
population. This is similar to the Delhi study. All these
studies have been performed using different tools by
different persons. However, the role of methodological
differences in producing biased results cannot be
overlooked. The present study, using methodology of JHW1 and JHW-2 shows that the prevalence of coronary risk
factors is significantly greater in the Bhatia community as
compared to previous studies in Jaipur (Table 5).
Studies of obesity in Asian subjects show that
generalized obesity is the major determinant of
cardiovascular risk in the Chinese and East Asian subjects
while central obesity is associated with greater cardio-
2/7/2005, 1:47 PM
Indian Heart J 2004; 56: 646–652
Gupta et al.
Jaipur Heart Watch-3 651
Table 4. Conditional logistic regression analysis for determining independent significance of obesity in metabolic
syndrome (odds ratios and 95% confidence intervals)
Variables
Obesity
Obesity + age
Obesity + age + hypertension
Obesity + age + hypertension + diabetes
Obesity + age + hypertension +
diabetes + truncal obesity
Men
Women
2.25 (1.68, 3.00)*
2.39 (1.77, 3.23)*
2.05 (1.48, 2.83)*
2.45 (1.69, 3.57)*
2.96 (2.13, 4.12)*
2.93 (2.03, 4.23)*
2.73 (1.81, 4.12)*
2.93 (1.86, 4.61)*
1.08 (0.68, 1.71)
1.09 (0.56, 2.11)
* p<0.001
≥ 30
vascular risk in South Asians.19 Deurenberg-Yap et al.20
determined body fat percentages (BF%) in Singaporean
Chinese, Malays and Indians and concluded that when the
BF% prediction equation based on BMI in Caucasian
populations was applied to these three ethnic groups in
Singapore, there was a gross underestimation of actual
BF%. The mean bias in prediction ranged from 2.7 to 5.6%
BF. They noted that for the same BMI values, Chinese have
the lowest BF% while Indians have the highest. The present
study shows that majority of cardiovascular risk factors in
Bhatia men and women increase at BMI of ≥25 kg/m2 and
therefore this cutoff, instead of BMI ≥30 kg/m2, should be
used to determine obesity in South Asians. Similar
Fig. 1. Body mass index (BMI) is directly correlated with prevalence of
metabolic syndrome indicating that obesity is associated with multiple metabolic
abnormalities in Punjabi Bhatia men and women (χ2 for trend p<0.0001).
recommendations have been made by other Indian
investigators21,22 as well as those from China and other
Asian countries.23 The present study also shows that BMI
levels accurately predict hypertension, diabetes and
metabolic syndrome in this community. BMI was not an
accurate predictor of lipid abnormalities. In the JHW-2
Table 5. Age-adjusted coronary risk factor prevalence in JHW-1, 1995, JHW-2, 2002 and JHW-3
JHW-1 (n=1415)
Smoking/tobacco
548/1415
(38.7)
Sedentary habits
1003/1415
(70.9)
History of diabetes
15/1415
(1.1)
158/1415
Obesity (BMI ≥27 kg/m2)
(11.2)
Truncal obesity:
128/250
Males >0.9, Females >0.8
(51.2)
Hypertension (≥140/90)
417/1415
(29.5)
Diabetes (history or fasting
glucose ≥126 mg/dl)
High total cholesterol
49/199
(≥200 mg/dl)
(24.6)
High LDL cholesterol
44/199
(≥130 mg/dl)
(22.1)
Low HDL cholesterol
86/199
(<40 mg/dl)
(43.2)
High triglycerides
53/199
(≥150 mg/dl)
(26.6)
Metabolic syndrome
-
Men
JHW-2 (n=550)
JHW-3 (n=226)
JHW-1 (n=797)
196/550
(35.6)
338/550
(61.5)
42/550
(7.6)
123/550
(22.3)
280/550
(50.9)
165/550
(30.0)
72/550
(13.1)
183/532
(34.4)
182/532
(34.2)
284/532
(53.4)
163/532
(30.6)
98/532
(18.4)
58/226
(25.7)*
90/226
(39.8)***
26/226
(11.5)***
87/226
(38.5)***
163/226
(72.2)*
98/226
(43.4)*
27/226
(11.9)
66/226
(29.1)
79/226
(35.0)*
166/226
(73.6)**
54/226
(23.9)*
72/226
(31.8)**
149/797
(18.7)
577/797
(72.4)
8/797
(1.0)
105/797
(13.2)
131/193
(67.9)
267/797
(33.5)
-
Women
JHW-2 (n=573)
JHW-3 (n=232)
69/573
(12.1)
362/573
(63.2)
49/573
(8.6)
170/573
(29.7)
388/573
(67.8)
174/573
(30.3)
65/573
(11.3)
243/559
(43.5)
254/559
(45.4)
303/559
(54.2)
160/559
(28.7)
173/559
(30.9)
4/232
(1.6)***
72/232
(31.2)***
32/232
(13.8)***
123/232
(53.0)***
186/232
(80.1)
127/232
(54.9)***
36/232
(15.4)***
69/232
(29.7)**
89/232
(38.4)
156/232
(67.3)
36/232
(15.4)**
118/232
(50.9)***
22/98
(22.5)
28/98
(28.6)
45/98
(45.9)
28/98
(28.6)
-
Values in parentheses are percentage. JHW-1: Jaipur Heart Watch-1 study; JHW-2: Jaipur Heart Watch-2 study; JHW-3: Jaipur Heart Watch-3 study;
BMI: body mass index; LDL: low-density lipoprotein; HDL: high-density lipoprotein * p<0.05, ** p<0.01,*** p<0.001
IHJ-736-04.p65
651
2/7/2005, 1:47 PM
652 Gupta et al.
study, we reported that BMI accurately predicts nonbiochemical coronary risk factors more accurately than
WHR while the latter is more reliable in predicting the
biochemical risk factors of hyperglycemia and lipid
abnormalities.24
Conclusions: Punjabi Bhatia community has a high
prevalence of obesity which is an important determinant
of cardiovascular risk factors. Although a lower BMI cutoff to diagnose obesity (≥ 25 kg/m2) is suggested by this
study, it needs to be confirmed by larger prospective
epidemiological studies. The INTERHEART case-control
study 25 of coronary risk factors in acute myocardial
infarction has recently reported that obesity, especially
central obesity, is an important coronary risk factor in most
of the developing countries of Asia, Europe, Africa and
South America. Community-wide preventive measures that
focus on obesity reduction are imperative.
Acknowledgements
Financial support was provided by a perpetual grant from
Monilek Hospital and Research Centre Trust, Jaipur. Logistic
support for this study was provided by Bhatia Hospital,
Bhatia Bhawan, Jaipur.
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Indian Heart J 2004; 56: 653–657
Ozerol et al.
Plasma Endothelin-1 in Patients with
L-R Shunts
653
Original
Article
Plasma Endothelin-1, Homocysteine and Serum Nitric
Oxide Values in Patients with Left-to-Right Shunt
Ibrahim H Ozerol, Feyzanur A Pac, Elif Ozerol, Erdal Ege, Saim Yologlu, Ismail Temel, Mustafa Pac
Departments of Clinical Microbiology, Pediatrics, Biochemistry, Cardiovascular Surgery and Biostatistics,
Faculty of Medicine, Inonu University, Malatya, Turkey
Background: This study aimed to evaluate the effect of pulmonary blood flow and pulmonary hypertension
on plasma endothelin-1, homocysteine and serum nitric oxide levels in patients with left-to-right shunt lesions
with pulmonary hypertension and also with normal pulmonary arterial pressure.
Methods and Results: Plasma endothelin-1, homocysteine and nitric oxide levels were measured in 44 patients
(Group 1) with left-to-right shunt and normal pulmonary arterial pressure (Qp/Qs: 2.1), 65 patients (Group 2)
with left-to-right shunt and pulmonary hypertension (Qp/Qs: 2.4), 20 healthy control subjects (Group 3), and
17 post-operative patients (Group 4). Plasma endothelin-1 and serum nitric oxide levels were significantly higher
in Group 2 than in groups 1, 3, and 4 (p<0.001). Plasma homocysteine levels were significantly higher in
Group 2 than in Groups 1 and 4 (p<0.001 and p<0.01, respectively).
Conclusions: The increase in serum nitric oxide levels in patients with left-to-right shunt and pulmonary
hypertension may be attributed to the compensatory mechanism. However, this increase does not improve
pulmonary hypertension because of increased endothelin-1 and homocysteine levels. In the light of present
study, we conclude that vascular changes caused by increased homocysteine and endothelin-1 may provoke
pulmonary hypertension in patients with left-to-right shunt. (Indian Heart J 2004; 56: 653–657)
Key Words: Congenital heart disease, Nitric oxide, Left-to-right shunt
U
nder physiologic conditions, the vascular endothelium
produces some factors that maintain normal vascular
tonus and homeostasis. Under pathologic conditions, two
of the most important factors produced by the vascular
endothelium are an endothelial-derived relaxing factor,
nitric oxide (NO) and an endothelial-derived vasoconstrictor
peptide, endothelin-1 (ET-1).1-3 ET-1 has potent physiologic
activities including vasoconstriction, cell proliferation,
edema, and possibly inflammation.4 Several studies have
demonstrated the interaction between NO and ET-1 in the
vascular endothelium. Endothelium-derived NO is known
as most potent endogenous vasodilator. Some studies
indicate that NO plays a major homeostatic role in
modulating vascular resistance.5,6 Blood vessels dilate in
response to increases in blood flow.7 It has been shown that
elevated plasma NO synthase (NOS) could explain the
increased basal release of endothelial NO due to high
pulmonary blood flow.8 Total plasma homocysteine (Hcy)
Correspondence: Dr Ibrahim Halil Ozerol, Associate Professor
Department of Clinical Microbiology, Faculty of Medicine, Inonu University
44069 Malatya, Turkey. e-mail: [email protected]
IHJ-604-04.p65
653
is now established as a clinical risk factor for coronary
artery disease (CAD), as well as other arterial and venous
occlusive diseases in adults.9 It is postulated that Hcy may
damage endothelial cells or act as a direct causal factor in
the thromboembolic process. Hcy potentiates vascular
tension in human umbilical artery possibly by suppressing
bioavailable NO and by the oxidative stress from Hcy
autooxidation.10 The prevalence of hyperhomocysteinemia
ranges from 20 - 40% in different populations with CAD. It
can contribute to the pathogenesis of pulmonary hypertension (PH) in patients with congenital heart disease.
In the present study, we investigated the level of plasma
ET-1, Hcy and serum NO levels in children having left-toright (L-R) shunt with or without PH and children with
surgically closed shunt.
Methods
We studied the children having L-R shunt older than 6
month of age. Patients with complex congenital heart
disease, metabolic disorders, renal disease, infection, systemic
hypertension and anemia were excluded.
2/7/2005, 1:47 PM
654 Ozerol et al.
Indian Heart J 2004; 56: 653–657
Plasma Endothelin-1 in Patients with L-R Shunts
The study was performed on four groups. Group 1
consisted of 44 patients with L-R shunt and normal
pulmonary artery pressure (NPAP); Group 2 had 65
patients having L-R shunt with PH; Group 3 included 20
normal control subjects; and Group 4 had 17 patients who
underwent L-R shunt closure surgery. Fourty-four patients
without PH were diagnosed as - 37 ventricular septal defect
(VSD), 5 atrial septal defect (ASD), and 2 ASD plus VSD; 65
children with PH were diagnosed as 36 VSD, 17 VSD plus
ASD, 5 VSD plus patent ductus arteriosus (PDA), and 7
atrioventricular (AV) canal defects. Post-operative patients
consisted of 11 VSD, 3 ASD and 3 AV canal defect. None of
the post-operative cases had PH on 6th month echocardiographic evaluation.
All patients were catheterized after midazolam or
ketamine sedation. Pressures of different chambers and
pulmonary artery mean pressure (PAMP) were recorded
by a fluid-filled and catheter-connected pressure transducer.
Pulmonary and systemic flows were calculated by Fick
method.
Blood samples of the patients were obtained from the
pulmonary artery during cardiac catheterization. Control
group consisted of normal healthy children and blood
samples were withdrawn from peripheral veins. The parents
of all participants were duly informed before blood
collection and consent was obtained from the parents of
patients and controls. In post-operative group, blood
samples were taken from peripheral veins at least 6 months
after surgery. ET-1 was measured by an enzyme
immunoassay (ELISA) kit (Endothelin-1 Enzyme
Immunoassay Kit, Cayman Chem, Ann Arbor, MI, USA)
and Hcy was analyzed by Axis Homocysteine ELISA kit
(Homocysteine Enzyme Immunoassay Kit, Bio-Rad Lab,
Oslo, Norway). Because NO is converted to nitrite and
nitrate just after production in vivo, serum nitrite and nitrate
levels was taken as an index of serum NO. By coloring with
Griess reagent after cadmium reduction, total nitrite (nitrite
+ nitrate) was determined by spectrophotometric method
using a visible spectrophotometer (LKB Biochrom
Spectrophotometer, Cambridge, UK).
Statistical analysis: All data was reported as mean ±
standard deviation (SD). All parameters were tested with
Kolmogrow-Smirnov test. If its distribution was not normal
(p>0.05), Mann-Whitney U test was used as dual
comparison.
Results
Endothelin-1, total homocysteine and NO levels in serum
of patients with L-R shunt both having PH and NPAP,
normal healthy persons, and a group of patients operated
for shunt were studied. Some characteristics of participants
and the values of ET-1, NO, and Hcy in different groups are
summarized in Table 1 and Figs 1, 2 and 3.
ET-1 and Hcy levels were higher in patients having PH.
NO levels were higher in patients with or without PH when
compared to the other groups. In post-operative patients,
ET-1, NO and Hcy levels were lower than those of preoperative patients having PH. Endothelin-1 levels in
patients with L-R shunt and NPAP were significantly lower
than those of other groups (p<0.001) except post-operative
patients. Patients with L-R shunt and NPAP and postoperative patients had significantly lower plasma ET-1 levels
than those of control subjects (p<0.001 in both). Similarly,
NO levels in patients with L-R shunt with PH were higher
compared to other groups (p<0.01). The serum NO levels
in L-R shunt patients with PH and post-operative patients
were higher compared to healthy persons (p<0.01 in both).
Plasma total Hcy levels in patients with L-R shunt with PH
were significantly higher compared to the patients with LR shunt with NPAP and post-operative patients (p<0.001,
p<0.01, respectively). There was a statistically significant
lower Hcy levels in patients with L-R shunt and NPAP
compared to healthy controls (p<0.01).
Discussion
Pulmonary hypertension seen in the patients with L-R
shunt may be partially related to increased pulmonary
blood flow. There are many other causes of PH, some of
Table 1. Characteristics of the patients and control groups and the results of parameters studied
Groups
No.
Age
(years)
ET-1
(pg/ml)
NO
(µmol/L)
Hcy
(µmol/L)
PAMP
(mmHg)
L-R shunt+NPAP
L-R shunt+PH
Healthy controls
Post-Op
44
65
20
17
5.3±5.2
4.4±4.9
3.9±4.1
5.5±4.8
1.1±0.5
26.7±7.1
11.8±5.1
1.0±0.5
22.3±19.6
30.5±44.9
7.2±4.5
12.7±9.4
8.2±2.1
12.8±4.8
10.7±4.4
8.6±2.9
16.6±3.3
42.1±17.5
–
–
Qp/Qs
2.1±0.7
2.4±1.1
–
–
ET-1: endothelin-1; NO: nitric oxide; Hcy: homocysteine; PAMP: pulmonary artery mean pressure; L-R: left-to-right; NPAP: normal pulmonary artery pressure; PH: pulmonary
hypertension; Post-Op: post-operation
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Indian Heart J 2004; 56: 653–657
Plasma endothelin-1 (pg/ml)
L-R Shunt
+NPAP
L-R Shunt
+PH
Healthy Controls
Post-Op
Groups
Serum nitric oxide (µmol/l)
Fig. 1. Plasma endothelin-1 levels in patients, healty controls and patients with
shunt operation.
Data represent the mean concentration ± standard deviation. L-R: leftto-right; NPAP: normal pulmonary artery pressure; PH: pulmonary
hypertension; Post-Op: post-operation; pg: picogram
* Significant difference compared to another groups (p<0.001)
# Significant difference compared to groups with L-R shunt plus PH and
post-operation (p<0.001 in both)
L-R Shunt
+NPAP
L-R Shunt
+PH
Healthy Controls
Post-Op
Groups
Fig. 2. Serum nitric oxide levels in patients, healty controls and patients with
shunt operation.
Data represent the mean concentration ± standard deviation. L-R: leftto-right; NPAP: normal pulmonary artery pressure; PH: pulmonary
hypertension; Post-Op: post-operation; µmol: micromol
* Significant difference compared to another groups (p<0.01)
# Significant difference compared to patients with L-R shunt plus PH and
post-operation (p<0.01 and p<0.05, respectively)
them are still unknown. The normal endothelium
elaborates a panoply of proteins, prostanoids, and other
paracrine substances to maintain a delicate balance
between vasoconstriction and vasodilation, coagulation
and blood fluidity, as well as inhibition and promotion of
vascular growth.7
IHJ-604-04.p65
Plasma Endothelin-1 in Patients with L-R Shunts 655
Plasma total homocysteine (µmol/l)
Ozerol et al.
655
L-R Shunt
+NPAP
L-R Shunt Healthy Controls
+PH
Groups
Post-Op
Fig. 3. Plasma total homocysteine levels in patients, healty controls and patients with shunt operation.
Data represent the mean concentration ± standard deviation; L-R: left-toright; NPAP: normal pulmonary artery pressure; PH: pulmonary
hypertension; Post-Op: post operation; µmol: micromol
* Significant difference compared to patients with L-R shunt plus PH and
post-operation (p<0.001, p<0.01, respectively)
# Significant difference compared to patients with L-R shunt plus PH
(p<0.01)
The endothelium responds to hemodynamic forces.
Blood vessels dilate in response to increased blood flow. The
integrity of endothelium is essential for this flow-mediated
vasodilation.11-13 Flow-mediated vasodilation is largely due
to the release of NO,7 which is known to modulate smooth
muscle growth, too. On the other hand, ET-1 produced by
vascular endothelial cells has potent vasoconstrictor and
mitogenic activities on vascular smooth muscle cells.14-16
ET-1 contracts isolated pulmonary vessels17 and increases
pulmonary vascular resistance (PVR).18 Endothelial injury
appears to be an important mechanism of enhanced release
of ET-1 in animal models.19,20
In our study, NO levels in L-R shunt patients with or
without PH were significantly higher than that of controls.
After surgical closure, NO values decreased. Although there
was no significant difference in QP/QS ratio between groups
1 and 2. The plasma ET-1 levels were significantly higher
in patients with PH than those without PH (p<0.001).
There was also a decrease of ET-1 level in post-operative
patients. Several studies have shown that plasma ET-1
levels are increased in patients with primary or secondary
PH.21-25 Yoshibayashi et al.25 reported an absolute increase
in ET-1 levels across the pulmonary circulation in patients
with congenital heart disease and PH compared with those
of non-PH group. Ishikawa et al. 26 demonstrated that
successful surgery decreased the elevated plasma ET-1 levels
from 3.96 to 1.98 pg/ml in young patients with PH caused
2/7/2005, 1:47 PM
656 Ozerol et al.
by congenital heart disease indicating that the elevation of
ET-1 in these patients was reversible. Increased ET-1 level
associated with PH was found to be correlated with the
severity of disease.23,25 In our three patients with PH, ET-1
levels were very high and decreased after surgery. Some
investigators could not establish a direct positive correlation
between increased blood flow and increased ET-1 levels.27,28
We also could not find such a correlation.
Increased plasma ET-1 levels can result from either an
increase in the production of ET-1 or a decrease of its
clearance. Dupuis et al.29 have shown that the metabolic
capacity of the lung to remove ET-1 from circulation greatly
reduces in PH. As a result of decreased clearance, the
quantity of ET-1 that survives passage through the lungs
increases in patients with PH. On the other hand, it has
been demonstrated that expression of ET-1 increases in the
pulmonary vascular endothelial cells of patients with PH.26
It may aggravate the pulmonary hemodynamics through
its potent and long-lasting vasoconstrictive as well as
proliferative actions on pulmonary arteries.26 Gorenflo et
al.28 reported that plasma ET-1 did not significantly differ
among patients with ASD, VSD and PDA. Hence, we did
not divide the patients into subgroups.
Several studies have demonstrated the interaction
between NO and ET-1 in the vascular endothelium. Some
investigators have reported an increased ET-1 and a
decreased NO production in patients with PH and in
experimental PH models.30-32 In our study, we found that
both ET-1 and NO levels were high in patients with PH.
The activation of a vasoconstrictor such as ET-1 on the
endothelium induces the release of NO.7 Flow-mediated
vasodilation is mostly related to NO release.7 It has been
also shown that elevated plasma NOS could explain the
increased basal release of endothelial NO due to high
pulmonary blood flow.8
A rise in Hcy plasma level is considered an independent
risk factor for the development of vascular damage. Two
major hypotheses have been proposed to explain how Hcy
induces its harmful effects. It can damage endothelial cells
lining the vasculature allowing plaque formation.
Simultaneously, it interferes with the vasodilatory effect of
NO. Hcy has also been found to promote vascular smooth
muscle cell hypertrophy. Both of these processes induce
vessel occlusion.33 A few studies have investigated Hcy levels
in children. De Laet et al.34 studied the reference range of
Hcy in Belgian pediatric population. In their study, total
Hcy concentrations were lowest in younger children, and
increased with age. In 5-9 year-old age group, Hcy
geometric means were 6.2 µmol/L (our mean values were
10.7 µmol/L in control group and 8.2 µmol/L in Group 1,
IHJ-604-04.p65
Indian Heart J 2004; 56: 653–657
Plasma Endothelin-1 in Patients with L-R Shunts
656
respectively). In our study, Hcy levels in PH group were
significantly higher than post-operative patients and
patients without PH (p<0.01 and p<0.001, respectively).
We could not find a significant difference between postoperative group and controls. Most of the operated patients
were from the group without PH. It is supposed that
hyperhomocysteinemia damages endothelial cells and
causes thromboembolic process, and these factors could
contribute to PH.
Increased pulmonary blood flow alone is not effective in
the development of PH. Vasoactive substances such as NO
and ET-1 and endothelial damaging agents such as Hcy
have important roles in the pathogenesis of PH. The reason
for increased ET-1 levels in PH , whether because of its overproduction or decreased clearance is not known precisely.
On the other hand, ET-1 has vasoconstrictive and
proliferation-stimulating effects and may cause PH. NO
levels increase in patients with high pulmonary blood flow
with or without PH. In the rats injected Hcy, endothelial
NOS increased 2-fold and inducible NOS 3-fold in aortic
endothelium.35 It is observed that although high levels of
Hcy and NO in PH were detected, Hcy has not only
endothelial damaging and thromboembolic effects, but it
also decreases the bioavailability of NO. Hence, NO level is
higher but less effective in PH.
Conclusions: Vascular changes caused by hyperhomocysteinemia may provoke PH in patients with L-R
shunt. Hyperhomocysteinemia which is seen in 9-15% in
general population36 should be investigated in these patients
and treated by folate and vitamin B12.
References
1. Giaid A. Nitric oxide and endothelin-1 in pulmonary hypertension.
Chest 1998; 114: 208S–212S
2. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991; 43: 109–142
3. Yanagisawa M. The endothelin system. A new target for therapeutic
intervention. Circulation 1994; 89: 1320–1322
4. Michael JR, Markewitz BA. Endothelins and the lung. Am J Respir
Crit Care Med 1996; 154: 555–581
5. Rees DD, Palmer RM, Moncada S. Role of endothelium-derived nitric
oxide in the regulation of blood pressure. Proc Natl Acad Sci USA
1989; 86: 3375–3378
6. Vallance P, Collier J, Moncada S. Effects of endothelium-derived nitric
oxide on peripheral arteriolar tone in man. Lancet 1989; 2: 997–
1000
7. Cooke JP, Dzau VJ. Nitric oxide synthase: role in the genesis of
vascular disease. Annu Rev Med 1997; 48: 489–509
8. Takaya J, Ikemoto Y, Teraguchi M, Nogi S, Kobayashi Y. Plasma nitric
oxide products correlate with cardiac index of congenital heart
disease. Pediatr Cardiol 2000; 21: 378–381
9. Langman LJ, Cole DE. Homocysteine. Crit Rev Clin Lab Sci 1999; 36:
365–406
2/7/2005, 1:47 PM
Indian Heart J 2004; 56: 653–657
Ozerol et al.
10. Okatani Y, Wakatsuki A, Reiter RJ. Protective effect of melatonin
against homocysteine-induced vasoconstriction of human umbilical
artery. Biochem Biophys Res Commun 2000; 277: 470–475
11. Cooke JP, Stamler J, Andon N, Davies PF, McKinley G, Loscalzo J.
Flow stimulates endothelial cells to release a nitrovasodilator that is
potentiated by reduced thiol. Am J Physiol 1990; 259: H804–H812
12. Pohl U, Holtz J, Busse R, Bassenge E. Crucial role of endothelium in
the vasodilator response to increased flow in vivo. Hypertension
1986; 8: 37–44
13. Young MA, Vatner SF. Blood flow- and endothelium-mediated
vasomotion of iliac arteries in conscious dogs. Circ Res 1987; 61:
II88–II93
14. Janakidevi K, Fisher MA, Del Vecchio PJ, Tiruppathi C, Figge J, Malik
AB. Endothelin-1 stimulates DNA synthesis and proliferation of
pulmonary artery smooth muscle cells. Am J Physiol 1992; 263:
C1295–C1301
15. Komuro I, Kurihara H, Sugiyama T, Yoshizumi M, Takaku F, Yazaki
Y. Endothelin stimulates c-fos and c-myc expression and proliferation
of vascular smooth muscle cells. FEBS Lett 1988; 238: 249–252
16. Yanagisawa M, Kurihara H, Kimura S, Goto K, Masaki T. A novel
peptide vasoconstrictor, endothelin, is produced by vascular endothelium and modulates smooth muscle Ca2+ channels. J Hypertens
1988; 6(Suppl): S188–S191
17. Ryan US, Glassberg MK, Nolop KB. Endothelin-1 from pulmonary
artery and microvessels acts on vascular and airway smooth muscle.
J Cardiovasc Pharmacol 1989; 13: S57–S62
18. Lippton HL, Hauth TA, Summer WR, Hyman AL. Endothelin
produces pulmonary vasoconstriction and systemic vasodilation. J
Appl Physiol 1989; 66: 1008–1012
19. Sugiura M, Inagami T, Kon V. Endotoxin stimulates endothelinrelease in vivo and in vitro as determined by radioimmunoassay.
Biochem Biophys Res Commun 1989; 161: 1220–1227
20. Pernow J, Hemsen A, Lundberg JM. Increased plasma levels of
endothelin-like immunoreactivity during endotoxin administration
in the pig. Acta Physiol Scand 1989; 137: 317–318
21. Cacoub P, Dorent R, Maistre G, Nataf P, Carayon A, Piette C, et al.
Endothelin-1 in primary pulmonary hypertension and the Eisenmenger syndrome. Am J Cardiol 1993; 71: 448–450
22. Rosenberg AA, Kennaugh J, Koppenhafer SL, Loomis M, Chatfield
BA, Abman SH. Elevated immunoreactive endothelin-1 levels in
newborn infants with persistent pulmonary hypertension. J Pediatr
1993; 123: 109–114
23. Stewart DJ, Levy RD, Cernacek P, Langleben D. Increased plasma
endothelin-1 in pulmonary hypertension: marker or mediator of
disease? Ann Intern Med 1991; 114: 464–469
IHJ-604-04.p65
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Plasma Endothelin-1 in Patients with L-R Shunts 657
24. Yamamoto K, Ikeda U, Mito H, Fujikawa H, Sekiguchi H, Shimada
K. Endothelin production in pulmonary circulation of patients with
mitral stenosis. Circulation 1994; 89: 2093–2098
25. Yoshibayashi M, Nishioka K, Nakao K, Saito Y, Matsumura M, Ueda
T, et al. Plasma endothelin concentrations in patients with
pulmonary hypertension associated with congenital heart defects.
Evidence for increased production of endothelin in pulmonary
circulation. Circulation 1991; 84: 2280–2285
26. Ishikawa S, Miyauchi T, Sakai S, Ushinohama H, Sagawa K, Fusazaki
N, et al. Elevated levels of plasma endothelin-1 in young patients
with pulmonary hypertension caused by congenital heart disease
are decreased after successful surgical repair. J Thorac Cardiovasc Surg
1995; 110: 271–273
27. Adatia I, Haworth SG. Circulating endothelin in children with
congenital heart disease. Br Heart J 1993; 69: 233–236.
28. Gorenflo M, Gross P, Bodey A, Schmitz L, Brockmeier K, Berger F,
et al. Plasma endothelin-1 in patients with left-to-right shunt. Am
Heart J 1995; 130: 537–542
29. Dupuis J, Cernacek P, Tardif JC, Stewart DJ, Gosselin G, Dyrda I, et al.
Reduced pulmonary clearance of endothelin-1 in pulmonary
hypertension. Am Heart J 1998; 135: 614–620
30. Giaid A, Saleh D. Reduced expression of endothelial nitric oxide
synthase in the lungs of patients with pulmonary hypertension. N
Engl J Med 1995; 333: 214–221
31. Miyauchi T, Yorikane R, Sakai S, Sakurai T, Okada M, Nishikibe M,
et al. Contribution of endogenous endothelin-1 to the progression
of cardiopulmonary alterations in rats with monocrotaline-induced
pulmonary hypertension. Circ Res 1993; 73: 887–897
32. Wong J, Reddy VM, Hendricks-Munoz K, Liddicoat JR, Gerrets R,
Fineman JR. Endothelin-1 vasoactive responses in lambs with
pulmonary hypertension and increased pulmonary blood flow. Am
J Physiol 1995; 269: H1965–H1972
33. Fanapour PC, Yug B, Kochar MS. Hyperhomocysteinemia: an
additional cardiovascular risk factor. WMJ 1999; 98: 51–54
34. De Laet C, Wautrecht JC, Brasseur D, Dramaix M, Boeynaems JM,
Decuyper J, et al. Plasma homocysteine concentration in a Belgian
school-age population. Am J Clin Nutr 1999; 69: 968–972
35. Wang S, Wright G, Harrah J, Touchon R, McCumbee W, Geng W, et
al. Short-term exposure to homocysteine depresses rat aortic
contractility by an endothelium-dependent mechanism. Can J
Physiol Pharmacol 2000; 78: 500–506
36. Pruefer D, Scalia R, Lefer AM. Homocysteine provokes leukocyteendothelium interaction by downregulation of nitric oxide. Gen
Pharmacol 1999; 33: 487–498
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658 Dugal
et al.
Brief
Report
Indian Heart J 2004; 56: 658–660
Angioplasty of Middle Cerebral Artery
Percutaneous Transluminal Angioplasty in an Embolic
Middle Cerebral Artery Occlusion
JS Dugal, Harminder Singh, Charanjit Singh, V Jetley, N Aggarwal, S Sofat, A Bahadur
Department of Cardiology, Military Hospital, Pune
A young lady developed left middle cerebral artery embolism after percutaneous transseptal mitral
commissurotomy. She was successfully treated with immediate percutaneous transluminal angioplasty. There
was complete recovery of neurological deficit. (Indian Heart J 2004; 56: 658–660)
Key Words: Angioplasty, Cerebrovascular disease, Percutaneous mitral commissurotomy
T
hromboembolism after percutaneous transseptal mitral
commissurotomy (PTMC) is a recognized but dreadful
complication.1-3 This most commonly happens to cerebral
vessels.2,3 Till lately, conservative treatment was the only
available option in this condition. However, in recent years
thrombolytic therapy and percutaneous transluminal
angioplasty (PTA) are being increasingly utilized to
reperfuse these vessels.4-6 There is increasing tendency to
resort to PTA. We report a case of middle cerebral embolic
occlusion following PTMC treated with PTA.
Case Report
A 20-year-old female had history of acute rheumatic fever
in 1994 and she developed rheumatic mitral stenosis in
1996 for which she underwent PTMC. She presented again
with progressive breathlessness of 6 months duration due
to severe mitral restenosis. On echocardiography, mitral
valve area was found to be 1.0 cm2 without any mitral
regurgitation. There was severe tricuspid regurgitation and
severe pulmonary artery hypertension with normal sinus
rhythm. Valve was considered suitable for PTMC. There was
no left atrial or left atrial appendage thrombus on
transesophageal echocardiography (TEE).
She (height 160 cm) was taken up for PTMC, which was
successfully performed with Inoue technique1 with single
dilation with balloon of 25 size under cover of 5000 units
of heparin. The end-diastolic gradient reduced to 2 mmHg
with no mitral regurgitation. The procedure went
uneventfully and she was shifted to the recovery room. She
developed right-sided hemiplegia with aphasia nearly 10
Correspondence: Professor Charanjit Singh, Head, Department of
Cardiology, Military Hospital and Cardiothoracic Center, Pune 411040
IHJ-723-04.p65
658
Fig. 1. Left internal carotid angiogram showing occlusion of middle cerebral
artery (MCA) just after its origin.
min after completion of the PTMC. She was diagnosed to
have embolic occlusion of middle cerebral artery (MCA).
The cause was thought to be thrombus formation during
PTMC. She was wheeled back into the cardiac
catheterization laboratory and four-vessel angiogram was
performed. There was no abnormality on bilateral vertebral
and right carotid angiograms. Left cerebral artery angiogram showed complete occlusion of the M1 segment of the
middle cerebral artery with no distal flow (Fig. 1). We
considered local delivery of thrombolytic therapy versus
immediate balloon angioplasty. She was taken up for PTA
after consent and discussion with the relatives.
2/7/2005, 1:50 PM
Indian Heart J 2004; 56: 658–660
Dugal et al. Angioplasty of Middle Cerebral Artery 659
Fig. 2. Angiogram following crossing with the wire.
Fig. 4. Balloon dilation of distal segment of middle cerebral artery.
Fig. 3. Angiogram after balloon dilation in proximal middle cerebral artery.
Left carotid artery was hooked with JR 3.5 6 F guide
catheter. Balanced middle weight coronary guidewire
(Guidant Corporation, Santa Clara, USA) was passed across
the occlusion (Fig. 2). Marked tortuosity of the vessels and
absence of any flow distally made it difficult to wire. A
1.5 × 10 mm balloon followed by 2.5 × 15 mm balloon
(Medtronic AVE, Minneapolis, USA) was positioned in MCA
and dilated at multiple sites at 2-4 atm pressure for 15-20 s
IHJ-723-04.p65
659
Fig. 5. Angiogram showing final result.
each (Figs 3 and 4). Thus, normal flow was restored (Fig. 5).
There was no residual lesion or distal embolization. The
procedure time was 65 min and fluoroscopy time, 22 min
following which she made rapid but incomplete recovery
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660 Dugal et al. Angioplasty of Middle Cerebral Artery
Indian Heart J 2004; 56: 658–660
right on the table, which subsequently progressed to
complete recovery within 24 hours.
to reduce chances of re-occlusion. Safety of stenting of
intracerebral vessels has been shown by recent trials.4-6
We decided to resort to PTA because the patient was still
in cardiac catheterization laboratory with arterial sheath
in place. Her stroke was clearly embolic with no suspicion
of any atherosclerotic disease. We expected a fast
recanalization of the artery if performed early. However,
relative inexperience, and complete occlusion of MCA with
difficulty in wiring an occluded tortuous vessel with no
distal collaterals were major challenges. We were rewarded
with complete recovery of neurological deficit in an
iatrogenic stroke.
Discussion
Thromboembolism after PTMC to cerebral vessels is known
complication.2,3 Till lately, conservative treatment was the
only choice. Recently thrombolytic therapy and PTA are
increasingly being utilized to reperfuse these vessels.4-6
However, there are only few centers where such measures
are employed. We recently embarked on direct PTA to
revascularize one such patient with due consent of her
relatives. The outcome was very rewarding.
Development of excellent hardware has made it possible
to reach intracranial vessels and perform PTA. Several
studies have shown feasibility and safety of PTA in
intracranial vessels though complication rates still remain
high.4-6 Complications include rupture of the vessel with
sub-arachnoid hemorrhage,4 spasm, distal embolization,4
dissection5 and stent thrombosis4,5 if stents are used.
Angioplasty of intracranial vessels is distinctly different
from coronary angioplasty. Intracranial vessels float freely
in sub-arachnoid space without any connective tissue
support. This makes them prone to rupture and therefore
they have to be dilated at low pressures ranging from 2-8
atm only. Intracranial vessels give rise to lenticulostriate
branches, which are difficult to visualize on angiograms,
and protect during angioplasty. Occlusion of these branches
may cause procedure-related neurological deficit. Leptomeningeal collaterals are poorly developed in acute
occlusions; therefore these vessels do not tolerate prolonged
dilations during angioplasty, which have to be short i.e. 1020 s. Cerebral vessels are prone to spasm and pose technical
difficulties due to tortuosity.
Thrombolytic therapy in MCA occlusions has been used
successfully but has distinct disadvantages.7 Thrombolytic
therapy leads to delayed and incomplete resolution of
thrombus. Nakano et al.7 compared 36 patients given
thrombolytic therapy with 34 patients undergoing PTA.
Recanalization was achieved in 63% cases following
thrombolysis as opposed to 91.2% cases with PTA. If
thrombolytic therapy is instituted late after endothelial damage has already taken place, there is possibility
of hemorrhagic transformation and neurological
deterioration despite arterial recanalization.8,9 Re-occlusion
after thrombolytic therapy is also common.10 As opposed
to this, PTA has advantage that it can expediently treat
embolic and also atherosclerotic disease, if present, without
enhancing chances of hemorrhagic transformation. 7
Operator may also choose to stent the stenotic area in order
IHJ-723-04.p65
660
Conclusions: Embolic stroke is common and can happen
during interventional procedures. While thrombolytic therapy
has been a standard therapy, there are several reports of successful treatment with PTA. Larger studies will be required to
better define the method of choice but at present limited reports
suggest that PTA is feasible, safe and effective means of
revascularization in middle cerebral artery occlusion.
References
1. Inoue K, Owaki T, Nakamura T, Kitamura F, Miyamoto N. Clinical
application of transvenous mitral commissurotomy by a new balloon
catheter. J Thorac Cardiovasc Surg 1984; 87: 394–402
2. Iung B, Cormier B, Ducimetiere P, Porte JM, Nallet O, Michel PL, et
al. Immediate results of percutaneous mitral commissurotomy.
Circulation1996; 94: 2124–2130
3. Arora R, Kalra GS, Murty GS, Trehan V, Jolly N, Mohan JC, et al.
Percutaneous transatrial mitral commissurotomy: immediate and
intermediate results. J Am Coll Cardiol 1994; 23: 1327–1332
4. Kim JK, Ahn JY, Lee BH, Chung YS, Chung SS, Kim OJ, et al. Elective
stenting for symptomatic middle cerebral artery stenosis presenting
as transient ischemic deficits or stroke attacks: short term arteriographical and clinical outcome. J Neurol Neurosurg Psychiatry 2004;
75: 847–851
5. Lee JH, Kwon SU, Lee JH, Suh DC, Kim JS. Percutaneous transluminal
angioplasty for symptomatic middle cerebral artery stenosis: longterm follow-up. Cerebrovasc Dis 2003; 15: 90–97
6. Lylyk P, Cohen JE, Ceratto R, Ferrario A, Miranda C. Angioplasty and
stent placement in intracranial atherosclerotic stenoses and
dissections. AJNR Am J Neuroradiol 2002; 23: 430–436
7. Nakano S, Iseda T, Yoneyama T, Kawano H, Wakisaka S. Direct
percutaneous transluminal angioplasty for acute middle cerebral
artery trunk occlusion: an alternative option to intra-arterial
thrombolysis. Stroke 2002; 33: 2872–2876
8. Yokogami K, Nakano S, Ohta H, Goya T, Wakisaka S. Prediction of
hemorrhagic complications after thrombolytic therapy for middle
cerebral artery occlusion: value of pre- and post-theraputic
computed tomographic findings and angiographic occlusive site.
Neurosurgery 1996; 39: 1102–1107
9. Okada Y, Yamaguchi T, Minematsu K, Miyashita T, Sawada T,
Sadoshima S, et al. Hemorrhagic transformation in cerebral
embolism. Stroke 1989; 20: 598–603
10. Tsai FY, Berberian B, Matovich B, Lavin M, Alfiery K. Percutaneous
transluminal angioplasty adjunct to thrombolysis for acute middle
cerebral artery rethrombosis. AJNR Am J Neuroradiol 1994; 15:
1823–1829
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Indian Heart J 2004; 56: 661–663
Pinto et al.
Wire Perforation for Pulmonary
Atresia
661
Brief
Report
Transcatheter Guidewire Perforation of the Pulmonary
Valve as a Palliative Procedure in Pulmonary Atresia with
Intact Interventricular Septum
Robin J Pinto, Bharat Dalvi
Glenmark Cardiac Centre, Mumbai
We report two cases of pulmonary atresia with intact interventricular septum in whom we successfully perforated
and performed balloon dilation of the atretic pulmonary valve using a simple guidewire technique. The technical
challenges of performing this procedure in small infants are highlighted. (Indian Heart J 2004; 56: 661–
663)
Key Words: Congenital heart disease, Pulmonary atresia, Balloon dilation
P
ulmonary atresia (PA) with intact interventricular
septum (IVS) is a complex congenital heart disease that
has a wide morphological spectrum with variable
prognosis. In those with a better prognosis, initial palliation
is by right ventricular decompression.1 Over the last few
years, transcatheter perforation of the pulmonary valve has
been increasingly used in the favorable forms of PA with
intact IVS having only a moderate right ventricular (RV)
hypoplasia and a patent infundibulum.2-5 The procedure
can be performed with the use of a simple guidewire, radiofrequency wire or laser.2,4,5 We report our experience with
two children who underwent successful perforation using
simple guidewire technique.
Case Reports
Case 1: A two-month-old boy weighing 3.4 kg presented
with increasing cyanosis and shortness of breath. The
oxygen saturation was 42%. Two-dimensional echocardiography and color Doppler examination revealed PA
with intact IVS. The pulmonary circulation was ductdependent and there was no right ventricle-dependent
coronary circulation. The tricuspid valve (TV) annulus
measured 6.5 mm and the pulmonary annulus measured
5.0 mm. There was only a moderate degree of RV hypoplasia. The patient underwent transcatheter perforation of
the pulmonary valve under general anesthesia. Vascular
Correspondence: Dr Robin Pinto, Glenmark Cardiac Centre
209 D, Dr Ambedkar Road, Flat No 10, Nandadeep, Ground Floor
Matunga (E), Mumbai 400019. e-mail: [email protected]
IHJ-721-04.p65
661
access was via the right femoral vein and left femoral artery.
Initial diagnostic angiography was performed in lateral
view with a 5 F NIH catheter positioned in the right
ventricle (Fig. 1A). After pinpointing the exact position of
the atretic pulmonary valve, the angiographic catheter was
exchanged for a 4 F, 3.5 curve right Judkin’s (JR 3.5)
catheter which was positioned just below the pulmonary
valve. The proximal hub of the catheter was connected to
a Tohey-Borst adaptor to enable scout angiograms
throughout the procedure. Through the JR catheter the
hard end of a 0.018” coronary angioplasty guidewire was
passed which tended to straighten the right coronary
catheter. It therefore had to be given a gentle curve so that
the JR catheter pointed posteriorly and a little superiorly.
After confirming the catheter position, a jab was made with
the wire pointing in such direction as to enter the lumen
of the main pulmonary artery (MPA) (Fig. 1B). Repeat scout
injections were performed to confirm whether the wire had
perforated the pulmonary valve and entered the lumen of
the MPA. Once this was confirmed, the hard end of the wire
was removed and the floppy end maneuvered through this
tiny hole and positioned in the distal right pulmonary
artery. A 1.5 mm coronary angioplasty balloon (Maverick,
Boston Scientific) was then passed over this wire and
attempts made to cross the pulmonary valve. This was
unsuccessful, hence the balloon was withdrawn and a right
coronary angioplasty Judkin’s guide catheter was
introduced. With the support of the guide catheter the
balloon easily crossed the valve and an initial inflationdeflation cycle was performed till the balloon waist
disappeared (Fig. 1C). Thereafter, sequential balloon
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Indian Heart J 2004; 56: 661–663
Wire Perforation for Pulmonary Atresia
dilations were performed with increasing sizes of coronary
angioplasty balloon catheters up to 3. 5 mm. Then, over
the same wire, a 6 mm and then an 8 mm valvuloplasty
balloon were used (Tyshak-II, Boston Scientific) till the
waist disappeared completely (Fig. 1D). The hemodynamics
before and after the procedure are summarized in Table 1.
Repeat angiography revealed excellent antegrade flow
in the MPA with a complete opening of the pulmonary
valve (Fig. 1E). At 6 months follow-up, he was asymptomatic with a saturation of 92% and a transpulmonic
gradient of 26 mmHg and grade 2/3 pulmonary
regurgitation.
perforate the pulmonary valve in a retrograde fashion.
Subsequently patient improved but presented again at 3
months of age. Repeat two-dimensional echocardiography
and color Doppler examination confirmed the presence of
PA with intact IVS. In addition, there was a fistula formed
by the attempted perforation of the valve, which resulted
in a tract across the posterior aspect of the pulmonary valve
through the IVS into the RV body. There was a gradient of
136 mmHg across the tract with pulmonary regurgitation.
The patient was taken up for perforation of the pulmonary
valve. This time initially itself the right Judkin’s guide
catheter (6F) and angioplasty assembly were used. Great
care was taken to avoid entering the pulmonary artery
through the fistula. The procedure was performed identical
to the one performed in the first case. Final pulmonary valve
dilation was performed using an 8 mm balloon. The
hemodynamic results are summarized in Table 1.
Angiographic findings before and after the procedure are
shown in Fig. 2 (A to D). At follow-up, echo-Doppler
evaluation revealed a gradient of 15 mmHg across the
pulmonary valve and the flow through the fistula had
become insignificant.
Fig. 1. A: Right ventricular angiography showing atretic pulmonary valve with
no antegrade flow. Arrow points to atretic pulmonary valve, B: Arrow points to
guidewire which has successfully perforated the atretic pulmonary valve to enter
the main pulmonary artery, C: 1.5 mm coronary angioplasty balloon inflated
across the pulmonary valve, D: Final dilation of the pulmonary valve using an
8 mm valvuloplasty balloon, E: Final right ventricular angiography in lateral
view showing widely open pulmonary valve with good antegrade flow into the
pulmonary arteries.
Table 1. Hemodynamics pre- and post-balloon dilation
Saturation (pre)
Saturation (post)
RV pressure–pre (mmHg)
RV pressure–post (mmHg)
PV gradient–pre (mmHg)
PV gradient–post (mmHg)
RV/LV pressure–pre
RV/LV pressure–post
Case1
Case 2
42%
80%
96
50
86
25
1.2
0.5
62%
85%
150
40
116
15
1.5
0.4
RV: right ventricular; PV: pulmonary valve; LV left ventricular
Case 2: A 3-month-old baby weighing 4.0 kg was
diagnosed as a case of PA with intact IVS at birth and
underwent a left classical Blalock-Taussig (BT) shunt at day
7 of life. At the time of surgery, an attempt was made to
IHJ-721-04.p65
662
Fig. 2. A: Balloon angiography of the right ventricle. Arrow points to fistulous
connection between the right ventricular outflow and the main pulmonary artery,
B: Right ventricular angiography in lateral view. Arrow points to the atretic
pulmonary valve, C: Balloon inflated across the pulmonary valve, D: Final right
ventricular angiography reveals a widely open pulmonary valve with excellent
antegrade flow into the pulmonary artery. Arrow shows marked reduction of
flow through the fistulous tract.
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Indian Heart J 2004; 56: 661–663
Discussion
Transcatheter perforation of pulmonary valve as a
palliative procedure in PA with intact IVS was introduced
for the first time by Qureshi et al. in 1991.6 It has subsequently been validated by numerous investigators.2-5
Choosing only those with favorable forms (as in our 2 cases)
decreases procedure-related morbidity and mortality.
Both our cases were more than 3 kg and had a patent
infundibulum. A recent study7 found a success rate of 85%
with a procedural mortality of 5% and morbidity of 12%.
The patient population in this series consisted of almost all
sick neonates in contrast to the relatively older age of our 2
patients.7 Procedural success was dependent on adequate
visualization of the RV outflow tract and this was best
profiled in the lateral view. Due to limitations imposed by
the weight of the neonates and small infants, contrast
quantity was of primary importance. We therefore used
up to a maximum of 6-7 ml/kg of the contrast and diluted
this further so as to allow a large number of contrast
injections to be made. This helped in accurate evaluation
of the pulmonary valve with respect to guide catheter and
the perforating guidewire. Our preference for perforation
was the hard end of a 0.018" coronary angioplasty
guidewire rather than the regular wire. The smaller wire
was used in the hope that if the RV outflow myocardium
was perforated inadvertently, it would not result in a major
pericardial effusion or tamponade. Reshaping the guidewire helped to a great extent in ensuring that the guide
catheter pointed in the direction of the MPA. One of the
operators should keep the guide catheter very steady before
jabbing the hard end of the guidewire. Inadvertent
movement of the catheter at this critical juncture can result
in perforation of the RV outflow tract at wrong place. Once
the perforation was successful, it is impossible to maneuver
the hard end of the wire into the distal branch pulmonary
artery or duct. Our strategy was to remove the wire at this
juncture and then attempt to pass the floppy end of the
same wire through the hole that has been made, and place
it in the distal right or left pulmonary artery. Due to the
extreme severity of the obstruction, the first balloon passed
was a very low profile coronary angioplasty balloon (1.5
mm, Maverick, Boston Scientific). The poor support
provided by the monorail system made it mandatory to take
coronary angioplasty guide catheter support for the balloon
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Pinto et al.
Wire Perforation for Pulmonary Atresia 663
to track across the pulmonary valve. The balloon size was
gradually increased, finally ending with the regular balloon
valvuloplasty catheters equal to 120% to 140% of the
annulus size. In various series, up to 75% of neonates
undergoing this procedure may still need a BT shunt or RV
outflow patch because the impaired RV compliance
prevents maintenance of adequate systemic saturations.7
In this situation, ductal stenting has also been performed
as an alternative palliative procedure with satisfactory
results.8 The favorable anatomy and the relatively older age
in both our patients, and the prior BT shunt in Case 2,
probably obviated the need for any additional surgery.
Although radiofrequency perforation is the procedure of
choice in most centers the world over, it is not available in
the majority of centers in India. This report of two cases
shows that guidewire perforation of the pulmonary valve
using easily available accessories is a feasible option in
infants with pulmonary atresia and intact IVS with
favorable anatomy (normal-sized RV). This pre-selection
may allow biventricular correction in the majority of such
patients with a lower mortality and morbidity.
References
1. de Leval M, Bull C, Stark J, Anderson RH, Taylor JF, Macartney FJ.
Pulmonary atresia and intact ventricular septum: surgical
management based on a revised classification. Circulation 1982; 66:
272–280
2. Gibbs JL, Blackburn ME, Uzun O, Dickinson DF, Parsons JM, Chatrath
RR. Laser valvotomy with balloon valvuloplasty for pulmonary
atresia with intact ventricular septum: five years’ experience. Heart
1997; 77: 225–228
3. Wang JK, Wu MH, Chang CI, Chen YS, Lue HC. Outcomes of
transcatheter valvotomy in patients with pulmonary atresia and
intact ventricular septum. Am J Cardiol 1999; 84: 1055–1060
4. Giusti S, Spadoni I, De Simone L, Carminati M. Radiofrequency
perforation in pulmonary valve atresia and intact ventricular
septum. G Ital Cardiol 1996; 26: 391–397
5. Justo RN, Nykanen DG, Williams WG, Freedom RM, Benson LN.
Transcatheter perforation of the right ventricular outflow tract as
initial therapy for pulmonary valve atresia and intact ventricular
septum in the newborn. Cathet Cardiovasc Diagn 1997; 40: 408–413
6. Qureshi SA, Rosenthal E, Tynan M, Anjos R, Baker EJ. Transcatheter
laser-assisted pulmonary valve dilation in pulmonic valve atresia.
Am J Cardiol 1991; 67: 428–431
7. Agnoletti G, Piechaud JF, Bonhoeffer P, Aggoun Y, Abdel-Massih T,
Boudjemline Y, et al. Perforation of the atretic pulmonary valve.
Long-term follow-up. J Am Coll Cardiol 2003; 41: 1399–1403
8. Siblini G, Rao PS, Singh GK, Tinker K, Balfour IC. Transcatheter
management of neonates with pulmonary atresia and intact
ventricular septum. Cathet Cardiovasc Diagn 1997; 42: 395–402
2/7/2005, 1:50 PM
664 Elangovan
Brief
Report et al.
Indian Heart J 2004; 56: 664–667
Left Ventricular Hydatid Cyst
Left Ventricular Hydatid Cyst with Myocardial Infarction
in a Patient with Severe Rheumatic Mitral Stenosis
S Elangovan, K Harshavardan, K Meenakshi, TS Swaminathan, P Murthy
Departments of Cardiology, Cardiothoracic Surgery and Barnard Institute of Radiology, Madras Medical College, Chennai
Cardiac echinococcosis is rare, and the most serious of all hydatid infestations. We report a case of 30-year-old
female who had a hydatid cyst, myocardial infarction and severe rheumatic mitral stenosis. Following mitral
valvotomy, the hydatid cyst and the left ventricular aneurysm were totally excised under cardiopulmonary bypass.
The patient was discharged on the post-operative day 15 with the advice to continue albendazole for 5 years.
(Indian Heart J 2004; 56: 664–667)
Key Words: Hydatid cyst, Echocardiography, Mitral stenosis
E
chinococcosis is a tissue infestation perpetuated by the
larvae of echinococcus granulosus, where man is the
accidental host, sheep the intermediate host and dog the
definitive host. Infestation occurs by intestinal and airborne
routes. Larvae reach the myocardium through the
coronary circulation and the distribution of the cyst in the
heart varies according to the blood supply. The left ventricle
(LV), having the most abundant supply, is most frequently
involved (55%-60%). The other sites include the right
ventricle (15%), the interventricular septum (IVS) (5-9%),
left atrium (LA) (8%), pericardium (8%), pulmonary artery
(7%) and the right atrium (RA) (3- 4%).1 When the scolices
reach the myocardium, they start cyst formation; the cysts
enlarge and protrude toward epicardium or endocardium.
Surgical resection is the only remedy. Cystectomy has a
high rate of complete recovery. Irrigation of the cyst with
scolicidal agents prior to excision is essential to avoid
anaphylactic reactions. Supplemental therapy with broad
spectrum antihelminthics is warranted to prevent
recurrences.
Case Report
A 30-year-old female presented with shortness of breath
of 2 years duration. She gave no history of handling dogs
or of having reared sheep. Clinical examination revealed
an accentuated first heart sound, a loud pulmonary
component of second heart sound and rumbling mid
diastolic murmur at the cardiac apex. With the clinical
Correspondence: Professor S Elangovan, “Annai’’, No. 7, 1st Main Road
T.S.D. Nagar, Arumbakkam, Chennai 600 106
IHJ-682-04.p65
664
diagnosis of rheumatic mitral stenosis, the patient was
further evaluated. Electrocardiogram (ECG) showed sinus
rhythm with left atrial enlargement and non-progression
of R waves in the anterior chest leads. We did not think of
myocardial infarction (MI), as cardiac space occupying
lesions also can produce ECG changes mimicking MI.
Echocardiogram revealed severe mitral stenosis (orifice area
0.7 cm2), mild aortic regurgitation and a large cyst in the
left ventricle (Figs 1a and 1b). The cyst measured 6 cm in
diameter and was multiloculated. Serology by immunoelectrophoresis was positive for echinococcus. Computerized tomographic (CT) scan and magnetic resonance
imaging (MRI) of the thorax revealed a well defined, nonenhancing, globular hypodense lesion (7.5×5 cm) with
multiple septations and a volume of 170 - 180 ml (Figs 2a
and 2b). The cyst appeared to be situated in the lower IVS
on the LV side and was seen compromising the LV cavity.
No pre-operative coronary angiogram was done as we did
not suspect MI in this young lady who had no symptoms of
coronary artery disease (CAD). Abdominal ultrasonogram
did not reveal similar cysts in the liver or elsewhere. The
patient was put on albendazole 15 mg/kg body weight in
2 divided doses for a period of 4 weeks before she was
submitted for surgery.
Under cardiopulmonary bypass, the LA was opened and
mitral valvotomy was preformed. Two pieces of thrombi in
the LA were removed. As the cyst was not visualized
through the mitral orifice, left ventriculotomy was done and
the cyst exposed (Fig. 3). Although the pre-operative CT
scan and MRI showed the cyst to arise from the lower IVS
at surgery, the origin of the cyst was from the apicoanterior
wall of the LV. The lower 2/3rd of the IVS was found to be
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Elangovan et al.
Left Ventricular Hydatid Cyst 665
Fig.1a. A transthoracic echocardiogram in parasternal long axis view showing
severe mitral stenosis with left ventricular hydatid cyst.
Fig. 2a. Magnetic resonance imaging demonstrating multiple septation of left
ventricular hydatid cyst – sagital section.
Fig. 1b. A transthoracic echocardiogram in apical four-chamber view showing
severe mitral stenosis with left ventricular hydatid cyst.
thinned out and the LV apex was aneurysmal, probably due
to MI. The left anterior descending coronary artery (LAD)
was obliterated in its middle and distal third. The cyst was
irrigated with 20% hypertonic saline and its wall was
opened. Multiple cysts, 10 to 20 in number, were totally
evacuated taking care to avoid spilling of its contents
(Fig. 4). The cyst wall was completely excised and the LV
was washed with hypertonic saline and iodine solutions.
After the cyst was totally excised, the apical LV aneurysm
was partially excised. A large defect surrounded by thinned
and scarred tissue was left behind in the apicoanterior wall
of the LV. This scarred tissue was used to strengthen the
suturing with Teflon pledgets while reconstructing the
defect in the apicoanterior wall. The post-operative period
was uneventful. Echocardiogram done on the post-
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665
Fig. 2b. Megnetic resonance imaging demonstrating multiple septation of left
ventricular hydatid cyst – transverse section.
operative day 10 revealed redundant myocardial edges
where the cyst was excised. There was no evidence of
remains of the cyst or its wall. The lower 2/3rd of the IVS
and the LV anterior wall were hypokinetic, the LV apex was
dyskinetic and there was moderate LV systolic dysfunction.
The LV apex was still dyskinetic because the LV aneurysm
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Left Ventricular Hydatid Cyst
Fig.3. Intraoperative picture showing left ventricular hydatid cyst.
Fig 5. Right anterior oblique view showing abrupt cut off in the left anterior
descending artery at its middle third.
Fig. 4. Multiple hydatid cysts removed on surgery.
was only partially excised and a portion of the fibrous wall
of the aneurysm was left behind to aid in the proper
reconstruction of the defect in the apicoanterior wall. She
was discharged on the post-operative day 15, with the
advice to continue albendazole for 5 years. Two months
later, on the first post-operative review, echocardiogram
revealed improvement in the global LV systolic function.
Selective coronary angiography was done. Although we
initially interpreted it as normal, after further evaluation it
was concluded that the LAD was abruptly cut off in its
middle third (Figs 5 and 6). The other coronary arteries
were normal.
Discussion
Cardiac echinococcosis, serious as it is, can sometimes be
totally asymptomatic till the cyst has grown to large
dimensions. The effects of cysts are usually due to pressure,
IHJ-682-04.p65
666
Fig. 6. Left lateral view showing abrupt cut off in the left anterior descending
artery at its middle third.
arrhythmias, angina, valvular dysfunction, pericardial
reaction, pulmonary or systemic embolism and anaphylactic reactions.2-4 In our patient, the symptoms were
attributed to the mitral stenosis and the cyst was noted only
during routine echocardiography. Cysts in the IVS and the
apicoanterior wall, as with our case, have been reported,
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Indian Heart J 2004; 56: 664–667
but are relatively rare. Cysts once diagnosed have to be
removed. The recent trend is for off-pump procedures for
cysts which are purely intramyocardial and for those
enlarging toward the epicardium.5 Cysts in the IVS and
those protruding into the LV cavity have to be excised only
under cardiopulmonary bypass as was done in our patient.
At surgery, irrigation with scolicidal agents is mandatory
to prevent anaphylaxis.5 We used 20% hypertonic saline
which is the safest. Compression of the right and the left
ventricular outflow tracts and conduction system producing conduction disturbances have been reported in
literature but this is the first time a hydatid cyst associated
with MI is being reported. The MI was probably due to
compression and obliteration of the LAD by the cyst.
Generally, compression of a vessel by a cyst results in angina
rather than MI, but exceptions can occur. Further, the
slowly occluding lumen of the vessel could have been totally
occluded by an embolus from the clot in the left atrial
appendage. The diagnosis of MI was entertained only at
the time of surgery. The chance occurrence of rheumatic
heart disease with the cardiac hydatid cyst has also not been
reported in literature. We followed the recommended dose
of albendazole. Cyst in the heart should alert one to look
for cysts elsewhere and our patient did not have any
extracardiac cyst.
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Elangovan et al.
Left Ventricular Hydatid Cyst 667
Conclusions: Once thought to be a formidable disease,
cardiac echinococcosis can now be effectively managed by
excellent non-invasive diagnostic imaging procedures and
equally effective surgical expertise and techniques. Cardiac
hydatidosis, a disease of varied presentations is, exemplified
in our case where a cardiac hydatid cyst was associated with
MI and severe rheumatic mitral stenosis. To our knowledge,
this combination is the first report in literature. Further
medical treatment is mandatory not only pre-operatively
but also post-operatively to prevent cyst recurrence.
References
1. Tetik O, Yilik L, Emrecan B, Ozbek C, Gurbuz A. Giant hydatid cyst in
the interventricular septum of a pregnant woman. Tex Heart Inst J
2002; 29: 333–335
2. Perez-Gomez F, Duran H, Tamames S, Perrote JL, Blanes A. Cardiac
echinococcosis: clinical picture and complications. Br Heart J 1973;
35: 1326–1331
3. Ege E, Soysal O, Gulculer M, Ozdemir H, Pac M. Cardiac hydatid cyst
causing massive pulmonary embolism. Thorac Cardiovasc Surg 1997;
45: 249–250
4. Maffeis GR, Petrucci O, Carandina R, Leme CA, Truffa M, Vieira R, et
al. Cardiac echinococcosis. Circulation 2000; 101: 1352–1354
5. Birincioglu CL, Tarcan O, Bardakci H, Saritas A, Tasdemir O. Off-pump
technique for the treatment of ventricular myocardial echinococcosis. Ann Thorac Surg 2003; 75: 1232–1237
2/7/2005, 1:51 PM
668 Mohindra
Brief
Report et al.
Indian Heart J 2004; 56: 668–669
Syncope in Rheumatic Fever
Syncope in a Middle Aged Male due to
Acute Rheumatic Fever
Rajat Mohindra, HS Pannu, Bishav Mohan, Naveen Kumar, HS Dhooria, Alok Sehgal, G Avasthi
Dayanand Medical College and Hospital, Ludhiana
Rheumatic fever is a multi system disease which occurs following infection with group A beta hemolytic
streptococcus. It is commonest in the age group of 5-15 years but can occur in adults also. First degree
atrioventricular block is a common manifestation of acute rheumatic fever and is included in the Jones criteria
but Wenckebacks phenomena and complete heart block are relatively rare manifestations of rheumatic fever.
Syncope occurring in acute rheumatic fever is also infrequently reported. We report the case of a 38-year-old
male with rheumatic carditis who had advanced atrioventricular block which resulted in syncope and required
a temporary pacemaker insertion. (Indian Heart J 2004; 56: 668–669)
Key Words: Rheumatic carditis, Syncope, Complete heart block
R
heumatic fever is generally classified as a connective
tissue disorder involving multiple organs.1 The clinical
manifestations of acute rheumatic fever follow group A
streptococcal infection. In 1944, T Duckett Jones proposed
the diagnostic criteria for rheumatic fever which were later
modified, revised and updated by American Heart
Association in 1992.2 Carditis, migratory polyarthritis,
syndehams chorea, erythema marginatum and
subcutaneous nodules are the major criteria while fever,
arthralgia, increased acute phase reactants and prolonged
PR interval are the minor criteria. Inspite of the general
complacency about first degree atrioventricular (AV) block
in acute rheumatic fever, abnormal conduction with
dysarrythmias, occasionally advanced AV block and rarely
Stokes-Adams attacks can occur in rheumatic fever and
may require pacing.3-7
Case Report
A 38 year-old male, truck driver by profession, was admitted
in our hospital with fever of 10 days duration. There was
no previous history of any cardiorespiratory complaints or
joint pains. There was no history of intake of any drugs.
His examination revealed a blood pressure (BP) of 130/90
mmHg, pulse of 100 beats per min (bpm) and fever of
101°F. General physical examination did not reveal any
erythema marginatum or subcutaneous nodules. CardioCorrespondence: Dr Bishav Mohan, Asstt. Professor, Hero DMC Heart
Institute, Ludhiana, Punjab 141 001
IHJ-745-04.p65
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vascular examination revealed a high pitched, blowing
pansystolic murmur (Grade 3), best heard at the apex and
radiating to the axilla. An S3 gallop rhythm could also be
appreciated. The investigations revealed leukocytosis with
erythrocyte sedimentation rate (ESR) of 120 mm/hour. The
anti-streptolysin-O (ASO) titre was 405 Todd units/ml and
C-reactive protein (CRP) was positive by latex method.
Routine biochemical investigations were normal. Three
blood cultures taken at specific intervals were sterile. Viral
markers and HIV status were negative. Chest X-ray showed
mild cardiomegaly. The electrocardiogram (ECG) at time of
admission showed first degree AV block with PR interval
of 0.24 s (Fig. 1a). Two-dimensional echocardiography (2D
echo) revealed moderate mitral regurgitation (MR) with
trivial aortic regurgitation (AR) and left ventricular ejection
fraction (EF) of 60%. There was no regional wall motion
abnormality (RWMA). Transesophageal echocardiogram
(TEE) confirmed the above findings and also confirmed the
absence of vegetation on any of the valves. As patient had
definite evidence of rheumatic carditis, he was started on
injectable penicillin and hydrocortisone. Two days after
admission, the patient complained of a sinking sensation.
ECG done at this time showed presence of Wenckebacks
phenomenon (Fig. 1b). Few hours later, the patient had a
syncopal attack and ECG revealed a complete heart block
(Fig. 1c). In view of a syncopal attack and presence of
complete heart block, a temporary pacemaker was inserted.
The AV block lasted for about 5 days and then regressed
in a stepwise fashion to first degree AV block. He improved,
and was discharged on day 10 of hospital stay with an
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Indian Heart J 2004; 56: 668–669
a
b
c
Fig. 1. Electrocardiogram showing (a) Normal sinus rhythm with prolonged
PR interval of 0.24 s (b) Wenckebacks phenomenon (c) Complete heart block.
advice to get prophylactic injection benzathine intramuscular penicillin every 3 weeks. His ECG done on
outpatient follow-up 10 days later was normal (Fig. 2).
Fig. 2. Electrocardiogram showing normal sinus rhythm.
Discussion
Incidence of acute rheumatic fever in older age group is
significantly lower as compared to younger age group. The
peak age of occurrence of rheumatic fever is 5-15 years6
but initial attacks of rheumatic fever occurring in 4th
decade have also been reported.7 Our patient fulfilled one
major and 3 minor Jones criteria and echocardiography
confirmed the evidence of valvular involvement. This
patient also had syncope which occurred secondary to
complete heart block. There was no history of intake of
drugs which could have slowed the AV conduction nor was
there any evidence of ischemic heart disease (IHD) as
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Mohindra et al.
Syncope in Rheumatic Fever 669
revealed by absence of RWMA on 2D echo. Thus it was
safely assumed that this 38-year-old male had acute
rheumatic fever which caused a complete heart block
resulting in syncope.
Advanced AV conduction defects are uncommon in
acute rheumatic fever as shown by Zalzstein et al.4 They
studied 65 children with acute rheumatic fever and showed
the presence of advanced AV block in 6% cases.5 A similar
prevalence of advanced AV block was also shown by Veasy
et al.5 in their study of 232 patients with rheumatic fever.
Advanced AV block in acute rheumatic fever is usually
temporary as shown by Veasy et al.5 Our patient required a
temporary pacemaker but his advanced AV block reverted
to first degree AV block in about 5 days. The genesis of
advanced AV block in rheumatic fever is thought to be
secondary to inflammation of the conducting tissue but
an underlying disease of the conducting tissue has to be
ruled out in an older patient.
Thus, diagnosis of acute rheumatic fever should be
considered in any young adult or middle aged patient
presenting with fever and advanced AV block of
undetermined etiology and an aggressive management
plan should be sought as this can significantly reduce the
morbidity and mortality among the young patients.
References
1. Dajoni AS, Rheumatic fever. In: Braunwald (ed) Heart Disease, 6th
ed, Philadelphia, 2001, p 2192
2. Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992
update. JAMA 1992; 268: 2069–2073
3. Lenox CC, Zuberbuhler JR, Park SC, Neches WH, Mathews RA, Zoltun
R. Arrythmias and Stokes-Adams attack in acute rheumatic fever.
Pediatrics 1978; 61: 599–603
4. Zalzstein E, Maor R, Zucker N, Katz A. Advanced atrioventricular
conduction block in acute rheumatic fever. Cardiol Young 2003; 13:
506–508
5. Veasy LG, Tani LY, Hill HR. Persistence of acute rheumatic fever in
the intermountain area of the United States. J Pediatr 1994, 124:
9–16
6. Kaplan EL. Rheumatic fever. In: Harrison’s (ed) Principles of Internal
Medicine, 15th ed.
7. Barold SS, Sischy D, Punzi J, Kaplan EL. Advanced atrioventricular
block in 39-year-old man with acute rheumatic fever. Pacing Clin
Electrophysiol 1998; 21: 2025–2028
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et al.
Brief
Report
Indian Heart J 2004; 56: 670–672
Transatrial Pacemaker Lead Implantation
Transatrial Permanent Pacing Lead Implantation in a
Patient of Ebstein’s Anomaly after One and Half Repair
Rajnish Juneja, Anita Saxena, Shiv Choudhary, Balram Airan
Departments of Cardiology and Cardiothoracic Surgery, All India Institute of Medical Sciences, New Delhi
Several innovative approaches have been described to achieve endocardial pacing in patients with operated
complex congenital heart diseases. We report herein a case of Ebstein’s anomaly who underwent a Hardy’s
repair with a bidirectional Glenn shunt, tricuspid valve annuloplasty and atrial septal defect closure following
which she developed complete heart block. The chest was reopened through the previous midsternotomy and a
screw-in lead implanted transatrially that resulted in optimal pacing thresholds. This technique offers a viable
alternative for endocardial pacing in peri-operative patients requiring permanent pacing. (Indian Heart J 2004;
56: 670–672)
Key Words: Pacemaker, Glenn shunt, Congenital heart disease
E
ndocardial pacemaker lead implantation is routinely
done through the superior vena caval (SVC) approach.
This route may be inaccessible in some patients because of
SVC thrombosis, multiple pre-existing leads, a prior Glenn
shunt or in patients with extracardiac total cavopulmonary connection (TCPC). In such patients epicardial
pacemakers have been used conventionally, though the
high incidence of exit blocks remains a concern.1,2 This has
been circumvented partially with the newer steroid-eluting
button electrode (4965, Medtronic Inc.) but results still do
not compare with endocardial pacing.3,4 Alternatively,
endocardial access has been attempted through femoral
veins,5 transiliac6 or transphepatic approches,7 through the
inferior vena cava8 or rarely directly through the right
atrium.9 The present report highlights the right atrial
approach in a young lady after a one and a half repair for
Ebstein’s anomaly.
showed situs solitus with atrioventricular and ventriculoarterial concordance, a 22 mm displacement of the
septal leaflet of the tricuspid valve (TV). There was severe
low pressure tricuspid regurgitation. Right ventricular (RV)
size was adequate with a mildly reduced RV function.
Cardiac catheterization and angiography were
performed as per standard protocols through the right
femoral route. Hemodynamic data of the patient is
summarized in Table 1. RV angiogram revealed severe
tricuspid regurgitation with a grossly enlarged RA. The
pulmonary arteries were confluent and good sized. The
patient underwent a Hardy’s repair with a bidirectional
Glenn shunt, TV annuloplasty and atrial septal defect (ASD)
closure. Post-operatively the patient was in complete heart
block (CHB) that did not recover over a week. The
underlying escape rhythm was slow and a decision was
Table 1. Hemodynamic data
Case Report
A 33-year-old lady was diagnosed to be having Ebstein’s
anomaly with class III exertional dyspnea. Chest X-ray
showed a cardiothoracic ratio of 65% and significant right
atrial enlargement. Pre-operative electrocardiogram (ECG)
revealed normal sinus rhythm with right bundle branch
block and right atrial (RA) enlargement. Echocardiogram
Correspondence: Dr Rajnish Juneja, Associate Professor of Cardiology
Cardiothoracic Sciences Centre, All India Institute of Medical Sciences
New Delhi 110 029. e-mail: [email protected]
IHJ-761-04.p65
670
SVC
RA
RV
PA
PCW
LV
Ao
Pressures
Oximetry
a 4-8 v 4-6
18-20/8-9
18/10 m12
a 8-10 v 8-10 m7
100/8-10
125/75-90
50.1
58.9
63.8
59.6
96.4
PVRI : 4.1 U/m2
SVC: superior vena cava; RA: right atrium; RV: right ventricle; PA: pulmonary artery;
PCW: pulmonary capillary wedge; LV: left ventricle; Ao: aorta; PVRI: pulmonary
vascular resistance index; m: mean
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Indian Heart J 2004; 56: 670–672
taken for an early permanent pacemaker implantation
instead of the usual waiting period of 2 weeks.
Several options—standard epicardial (steroid-eluting
button electrode), transhepatic or transfemoral/transiliac
approach were considered for implanting the permanent
pacemaker. Transhepatic approach was considered unsafe
in view of patient’s RV dysfunction and congestive heart
failure. Transfemoral and transiliac procedures were not
done because of lack of experience and the fear of lead
damage because of repeated squatting that is a common
posture amongst Indians. It was decided to go transatrially
as this was an early post-operative period and the sternum
could be easily reopened.
The sternum was opened and a direct needle puncture
made into the low anterior right atrium and a 9 F peel away
sheath inserted into the RA. A screw in lead (4068,
Medtronic Inc.) was inserted into the right atrium under
fluoroscopic guidance but could not be manipulated into
the RV. The sheath was removed and this incision was
closed. The same sheath was then inserted higher into the
RA, at the SVC-RA junction avoiding the sinoatrial nodal
area. Manipulation into the RV was easy from this site and
the lead was placed in the right ventricular outflow tract
Fig. 1. Chest X-ray, PA view showing a dilated heart with an enlarged right
atrium. A pacemaker lead can be seen entering the right atrium directly (notice,
there is no lead in SVC) and screwed into the high septal RV wall. A button
electrode (arrow) is also seen that has been left in the subrectus pocket.
SVC: superior vena cava; RV: right ventricular
IHJ-761-04.p65
671
Juneja et al.
Transatrial Pacemaker Lead Implantation 671
(RVOT)/mid interventricular septum (Fig. 1). The lead was
screwed in connected to a VVIR (Medtronic Sigma 203)
pacemaker. The implant parameters were found satisfactory
(amplitude threshold at 0.5 ms was 0.9 V, impedance 730
ohms and an R wave of 15.5mV). As a back-up, a steroideluting button electrode (Medtronic, 4965) was also
sutured over the RV anterior wall (implant parameters:
amplitude threshold 2 V at 0.5 ms, impedance 540 ohms
and R wave of 6.8 mV). The pacemaker was put in an
abdominal subrectal pocket. Post-operative course was
uneventful. Interrogation 3 months post-implant revealed
an amplitude threshold <0.5 V at 0.4 ms pulse width and
a pulse width threshold of <0.18 ms at 2.5 V. The
pacemaker was programed to 3 V × 0.4 ms, 60-120 beats
per minute (bpm). The epicardial wire could obviously not
be interrogated at this stage.
Discussion
Permanent pacemaker implantation in neonates and
infants and in patients with complex congenital heart
diseases wherein access to the atrium has been lost from
the SVC has traditionally been done epicardially.10 Earlier,
epicardial systems were fraught with high thresholds at
implantation and exit blocks along with early battery
depletion and occasional deaths. 1 The steroid-eluting
button electrode seems to have obviated many of the
problems and thresholds nearly as good as endocardial
pacing have been reported.3,4 However, implant requires a
limited sternotomy and low thresholds may be difficult to
get on a scarred atrium or ventricle and the initial low
impedance may be a source of significant current drain.11
Our own experience with the epicardial electrodes has been
similar with a significant number of early failures/revisions
with the screw-in/fish type electrode, but better early
outcomes with the button electrode.12 The transfemoral/
transiliac route was not favored in our patient, in view of
her right ventricular dysfunction and elevated RA pressures
that could have resulted in deep vein thrombosis with its
antecedent complications. Temporary femoral venous
pacing has been shown to have up to a 30% incidence of
venous thrombosis.13
Transhepatic pacing was another option but was not
considered in this patient due to lack of previous experience
with this procedure. Elevated RA pressures may
theoretically pose a higher risk but this approach has been
safely performed in patients with previous Fontan surgery,
and therefore, is not contraindicated. 7 We, therefore,
decided to proceed with an approach that, though rarely
used, seemed logical and better.9
2/7/2005, 1:53 PM
672 Juneja et al.
Technically, direct right atrial entry was straightforward.
The risk of air embolism is likely to be the same as the
subclavian/axillary approach. Puncture should probably
be done high in the atrium, as it may be more difficult to
manipulate from below in a big atrium. Furthermore, a
high puncture makes one manipulate in the same way as
in a routine endocardial placement that is familiar to most
cardiologists. It may be preferable to use a long sheath (like
a coronary sinus sheath) that reaches the RV apex/outflow
and push the lead through it, as it is difficult to manipulate
the lead in this situation. Long-term thresholds have been
similar to any other endocardial lead.
To conclude, the suggested alternative route for endocardial pacing is specially suited for peri-operative patients
requiring permanent pacing.
References
1. Sachweh JS, Vazquez-Jimenez JF, Schondube FA, Daebritz SH, Dorge
H, Muhler EG, et al. Twenty years experience with pediatric pacing:
epicardial and transvenous stimulation. Eur J Cardiothorac Surg 2000;
17: 455–461
2. Villafane J, Austin E. Cardiac pacing problems in infants and children:
results of a 4-year prospective study. South Med J 1993; 86: 784–
788
3. Ten Cate FU, Breur J, Boramanand N, Crosson J, Friedman A, Brenner
J, et al. Endocardial and epicardial steroid lead pacing in the neonatal
and pediatric age group. Heart 2002; 88: 392–396
IHJ-761-04.p65
Indian Heart J 2004; 56: 670–672
Transatrial Pacemaker Lead Implantation
672
4. Sliz NB Jr, Johns JA. Cardiac pacing in infants and children. Cardiol
Rev 2000; 8: 223–239
5. Costa R, Filho MM, Tamaki WT, Crevelari ES, Nishioka SD, Moreira
LF, et al. Transfemoral pediatric permanent pacing: long-term results.
Pacing Clin Electrophysiol 2003; 26: 487–491
6. Ellestad MH, French J. Iliac vein approach to permanent pacemaker
implantation. Pacing Clin Electrophysiol 1989; 12: 1030–1033
7. Adwani SS, Sreeram N, DeGiovanni JV. Percutaneous transhepatic
dual chamber pacing in children with Fontan circulation. Heart
1997; 77: 574–575
8. West JN, Shearman CP, Gammage MD. Permanent pacemaker
positioning via the inferior vena cava in a case of single ventricle
with loss of right atrial-vena cava continuity. Pacing Clin Electrophysiol 1993; 16: 1753–1755
9. Hanseus K, Sandstrom S, Schuller H. Emergency pacing and
subsequent permanent pacemaker implantation in a premature
infant of 1770 g with a follow-up of 6 years. Pediatr Cardiol 2000;
21: 470–473
10. Fishberger SB, Wernovsky G, Gentles TL, Gamble WJ, Gauvreau K,
Burnett J, et al. Long-term outcome in patients with pacemakers
following the Fontan operation. Am J Cardiol 1996; 77: 887–889
11. Serwer GA, Dorostkar PC, LeRoy SS. Pediatric Pacing and defibrillation usage. In: Ellenbogen KA, Neal Kay G, Wilkoff BL (eds).
Clinical Cardiac Pacing and Defibrillation. 2nd ed. Pennsylvania: WB
Saunders Publishing Co; 2000, p 967
12. Ramakrishnan S, Juneja R, Shah S, Bhan A, Choudhary S, Kothari
SS, Saxena A, Airan B. Initial Experience with steroid-eluting button
epicardial permanant pacing leads [Abstr]. Indian Heart J 2003; 55:
493
13. Pandian NG, Kosowsky BD, Gurewich V. Transfemoral temporary
pacing and deep vein thrombosis. Am Heart J 1980; 100:
847–851
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Indian Heart J 2004; 56: 673–676
Singh et al.
Dilation and Thrombolysis of a Blocked
Shunt
673
Brief
Report
Thrombolysis with Percutaneous Transluminal Balloon
Angioplasty of a Blocked Modified Blalock-Taussig Shunt
V Singh, S Pillai, S Kulkarni, KS Murthy, R Coelho, B Ninan, KM Cherian
Departments of Pediatric Cardiology and Cardiothoracic Surgery,
Institute of Cardiovascular Diseases, Madras Medical Mission, Chennai
Transcatheter balloon recanalization of occluded Blalock-Taussig shunts in the early post-operative period has
been reported in the past but there are issues regarding the role of thrombolysis in this situation. We present
our experience with such a procedure in an infant with blocked modified Blalock-Taussig shunt. (Indian Heart
J 2004; 56: 673–676)
Key Words: Blalock-Taussig shunt, Balloon angioplasty, Thrombolysis
S
ystemic to pulmonary artery shunt is an established
palliative treatment to increase pulmonary blood flow
in cyanotic congenital heart diseases. The incidence of
acute and subacute blockage of a modified Blalock -Taussig
(BT) shunt is reported to be around 3%.1 The important
causes of shunt blockage include thrombosis in a
polycythemic child due to reduced intravascular volume,
subsequent to fever and dehydration, or distortion of the
pulmonary arteries leading to stenosis at the pulmonary
artery end. Previously, surgical revision of the shunt was
the only option available but in the last decade,
transcatheter recanalization of the blocked shunt is
developing as an important modality of management in
such patients.2–7 We hereby report a case of successful
transcatheter dilation and thrombolysis of a blocked right
modified Blalock-Taussig shunt (RMBTS) due to
thrombosis.
Case Report
A four-month-old male infant weighing 5.5 kg, was referred
to our institute with history of cyanotic spells since 20 days
of age. Cardiac examination revealed a single second heart
sound and ejection systolic murmur in the left second
intercostal space. The child had systemic oxygen saturation
of 65-70% in room air. Transthoracic echocardiography
(TTE) with color flow imaging revealed dextrocardia,
corrected transposition of the great arteries, subaortic
Correspondence: Dr Snehal Kulkarni, Consultant, Pediatric Cardiology,
Institute of Cardiovascular Diseases, Madras Medical Mission, 4A Dr JJ Nagar,
Mogappair, Chennai 600 050. e-mail: [email protected]
IHJ-311-02.p65
673
ventricular septal defect (VSD), pulmonary atresia with
hypoplastic confluent pulmonary arteries measuring 4 mm
each [Z score: right pulmonary artery (RPA) = -1.9 and left
pulmonary artery (LPA) =-1.62] and restrictive patent
ductus arteriosus (PDA). The infant underwent RMBTS
using 4 mm polytetrafluoroethylene tube. The surgery was
uneventful but the child required prolonged post-operative
ventilatory support due to culture-positive respiratory
infection, hyperreactive airways and diaphragmatic paresis
and he was extubated after 3 weeks once the above
mentioned factors were appropriately dealt with. TTE with
color flow imaging immediately after extubation revealed
a functioning RMBTS with an adequate shunt flow seen in
the pulmonary arteries. Subsequently the child was
clinically stable with oxygen (O2) saturation of 70% and was
continued on aspirin 4 mg/kg/day, along with rest of the
supportive management. After 4 days, the child had a sudden
episode of desaturation (O2 saturation: 40% on 4 L/min O2),
with tachypnea and mild alteration of sensorium. A TTE with
color flow imaging revealed a non-functioning RMBTS. A
transcatheter balloon angioplasty was planned, and the
infant was taken for cardiac catheterization under general
anesthesia. Right femoral vein (5 F) and artery (4 F) were
cannulated. Heparin bolus was given at a dose of 50 units/
kg body weight. Right subclavian artery angiography revealed a completely occluded RMBTS with a small proximal
stump (Fig. 1). The RMBTS was probed with a 0.025"
Terumo wire (Terumo Corporation, Tokyo, Japan) over which
a Judkin's right diagnostic catheter (JR 3.5) was advanced
into the proximal stump of the shunt and then into the left
pulmonary artery, and the wire was replaced with a straight
0.018"/300 cm exchange wire, which was advanced across
2/7/2005, 1:53 PM
674 Singh et al.
Indian Heart J 2004; 56: 673–676
Dilation and Thrombolysis of a Blocked Shunt
Fig. 1. Right subclavian artery angiogram revealing a totally occluded right
modified Blalock-Taussig shunt (RMBTS) at the aortic end.
Fig. 3. Post-dilation angiogram of the right subclavian artery revealing flow in
the right modified Blalock-Taussig shunt with a significant thrombus extending
throughout the length of the shunt.
Fig. 2. Angiogram demonstrating balloon dilation of the right modified BlalockTaussig shunt with a 4×20 mm balloon.
Fig. 4. Post-thrombolysis angiogram after 24 hours, revealing adequate flow
in the right modified Blalock-Taussig shunt.
the shunt and its tip positioned in the distal LPA. A
Symmetry balloon (4 mm × 20 mm) (Fig. 2) was positioned
across the occluded shunt and inflated thrice along the
blocked shunt with 1st inflation at 7 atm and 2nd and 3rd
inflations distally at 3 atm.
A repeat angiography in BT shunt revealed good
antegrade flow across the RMBTS, with evidence of a
thrombus in the distal shunt extending into the RPA
(Fig. 3). In view of the extensive thrombosis of the shunt,
local thrombolysis was administered. Urokinase (4400
units/kg) was injected in the RMBTS locally, over 10
minutes; it was continued as a systemic infusion at 4400
units/kg/hour for the next 24 hours. Post-procedure,
systemic oxygen saturation was 70%. A check angiography
after 24 hours of thrombolysis (Fig. 4) revealed a patent
RMBTS with a good flow into the RPA and a competitive
flow into the LPA through the PDA, with mild narrowing
of the proximal RPA. Heparin infusion at 10 units/kg/hour
replaced urokinase after 24 hours and was continued for
72 hours, with APTT monitoring. The child was also
simultaneously started on warfarin 0.1 mg/kg/day, which
was continued, along with aspirin for 3 months. The infant
was clinically stable with O2 saturations >70% at room air
and TTE with color flow imaging after 48 hours revealed
functioning RMBTS.
On follow-up after 3 months, the child was asymptomatic with O2 saturation of 75% at room air and had a
significant weight gain. TTE with color flow imaging on
follow-up revealed functioning RMBTS, and good-sized
branch pulmonary arteries.
IHJ-311-02.p65
674
Discussion
Transcatheter recanalization of a compromised systemic
to pulmonary artery shunt provides a feasible and effective
way to restore or increase the pulmonary blood flow.
2/7/2005, 1:53 PM
Indian Heart J 2004; 56: 673–676
Singh et al.
Fischer et al.2 reported the first successful balloon
dilation of an obstructed BT shunt in 1985, in a case of
complex cyanotic heart disease. In 1988, Marx et al.3
reported a series of 6 BT shunt dilations with suboptimal
results, with clear success obtained in only 2 patients. The
investigators suggested that the suboptimal results might
be due in part to the strict limitations placed on maximum
balloon diameter. In 1989, Qureshi et al.4 reported three
successful balloon dilations of stenotic BT shunts. There
are several other reports of dilation of BT shunts. 5-7
Thrombolysis after BT shunt dilation was used by Marasini
et al.6
Transcatheter dilation and local thrombolysis was first
reported by Robinson et al.8 in two cases with RMBTS, aged
5 months and 10 years respectively, with significant
improvement in saturation and complete restoration of
shunt patency. Ries et al.9 in 1994 reported thrombolysis
with recombinant tissue plasminogen activator in a
modified BT shunt in a 10-day old infant, 4 days after
surgery for complete shunt thrombosis. It resulted in
complete clot dissolution and reperfusion without
hemorrhagic complication. In this case, thrombolysis was
considered safe even 4 days after surgery.
Balloon dilation along with local thrombolysis of a
thrombosed occluded shunt results in mechanical
thrombus disruption and an increase in the surface area
of thrombus susceptible to pharmacological thrombolysis,
thus increasing the efficacy of the thrombolytics
administered as an infusion over the next 48-72 hours.9
There is always an issue as to how early, the thrombolysis
can be administered in case of occlusion of RMBTS
immediately after surgery. According to the standard
guidelines, thrombolytic agents can be administered safely
after 10 days of any surgical procedure.10 The management
of thrombosed systemic to pulmonary artery shunts, with
balloon dilation and thrombolysis, holds considerable
promise, as it avoids a repeat surgical procedure with its
inherent morbidity and mortality. Complications associated
with thrombolytic therapy for thrombosed BT shunts in
early post-operative period include serious bleeding
requiring transfusion and also possibility of excessive
bleeding during reoperation if thrombolytic therapy fails.
In our patient, the distal anastomatic site of the
RMBTS was stenosed which could have led to the
alteration of the laminar blood flow in the shunt and
subsequent thrombosis. Following administration of
urokinase infusion for 24 hours, the thrombus was
significantly reduced which was confirmed on check
angiography done after 24 hours. As the flow observed in
RMBTS subsequent to balloon angioplasty and
IHJ-311-02.p65
675
Dilation and Thrombolysis of a Blocked Shunt 675
thrombolysis was satisfactory, stent deployment was not
considered in this case.
Stent implantation is an attractive alternative therapy
for shunt stenosis or occlusion due to thrombosis,
particularly in the immediate post-operative period, when
fibrinolytic therapy may be hazardous. There are many
reports of stent placement in blocked BT shunt for
restoration of its patency. Zahn et al.11 reported in 1997,
an emergency stent deployment for acute BT shunt
obstruction after stage I Norwood surgery in a neonate at
8 days of life with immediate clinical improvement and
shunt patency maintained on 5-month follow-up. Lee et
al.12 reported a series of 13 patients who underwent stent
implantation for restoration of aortopulmonary shunt
patency. All patients had improved saturations subsequent
to stent implantation.
Peuster et al. 13 reported successful transcatheter
recanalization and subsequent stent implantation in 2
infants with post-operative thrombosis of modified BT
shunts. Both patients had shunt thromboses in the
immediate post-operative period, with significant
improvement in saturation and complete shunt patency
which was maintained on 3 months follow-up. Bader et al.14
reported the use of balloon-expandable stents in stenosed
BT shunts in 3 patients aged 23 to 32 years with mixed
results. One patient had a procedural failure due to stent
migration. A recent study by Sivakumar et al.15 reported
stent implantation to restore the patency of acutely
thrombosed modified BT shunt in 2 cases with residual
stenosis following transcatheter balloon dilations. One
patient developed acute stent thrombosis, which was
managed successfully with local thrombolysis. At 6 and 12
months follow-up, both the stented patients maintained
patent shunts with adequate oxygen saturation. Stent
implantation helps avoid the complications associated
with fibrinolytic therapy as well as reoperation with its
associated morbidity and mortality. Balloon angioplasty
and stent implantion reduce scar formation, and therefore,
improve the outcome of the patient at subsequent
corrective operative therapy. Angioplasty and stent
deployment should be performed very carefully, with
adequate sized balloons, since overexpansion may lead to
rupture of the sutures.
References
1. Drake HD, Complications related to the pulmonary artery. In:
Waldhausen AJ, Orringer BM (eds). Complications in Cardiothoracic
Surgery. Mosby: Year book Inc., 1991; p 150
2. Fischer DR, Park SC, Neches WH, Beerman LB, Fricker FJ, Mathews
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3.
4.
5.
6.
7.
8.
9.
IHJ-311-02.p65
Indian Heart J 2004; 56: 673–676
Dilation and Thrombolysis of a Blocked Shunt
RA, et al. Successful dilatation of a stenotic Blalock-Taussig
anastomosis by percutaneous transluminal balloon angioplasty.
Am J Cardiol 1985; 55: 861–862
Marx GR, Allen HD, Ovitt TW, Hanson W, Balloon dilation
angioplasty and Blalock-Taussig shunts. Am J Cardiol 1988; 62:
824–827
Qureshi SA, Martin RP, Dickinson DF, Hunter S. Balloon dilatation
of stenosed Blalock-Taussig shunts. Br Heart J 1989; 61:
432–434
Marks LA, Mehta AV, Marangi D. Percutaneous transluminal balloon
angioplasty of stenotic standard Blalock-Taussig shunts: effect on
choice of initial palliation in cyanotic congenital heart disease. J Am
Coll Cardiol 1991; 18: 546–551
Marasini M, Dalmonte P, Pongiglione G, Dolcini G, Bosoni M,
Ribaldone D, et al. Balloon dilatation of critically obstructed modified
(polytetrafluoroethylene) Blalock-Taussig shunts. Am J Cardiol 1994;
73: 405–407
Ormiston JA, Neutze JM, Calder AL, Hak NS. Percutaneous balloon
angioplasty for early postoperative modified Blalock-Taussig shunt
failure. Cathet Cardiovasc Diagn 1993; 29: 31–34
Robinson A, Fellows KE, Bridges ND, Rome JJ. Effectiveness of
pharmacomechanical thrombolysis in infants and children. Am J
Cardiology 2001; 87: 496–499
Ries M, Singer H, Hofbeck M. Thrombolysis of a modified Blalock-
676
10.
11.
12.
13.
14.
15.
Taussig shunt with recombinant tissue plasminogen activator in a
newborn infant with pulmonary atresia and ventricular septal defect.
Br Heart J 1994; 72: 201–202
Majerus WP, Broze JE, Miletich PJ, Tollefson MD. Anticoagulants,
thrombolytics and antiplatelet drugs. In; Hardman GJ, Limbird EL
(eds). Goodman and Gillman's The Pharmacological Basis of
Therapeutics. 9th ed. Mc Graw Hill, p 1353
Zahn EM, Chang AC, Aldousany A, Burke RP. Emergent stent
placement for acute Blalock-Taussig shunt obstruction after stage 1
Norwood surgery. Cathet Cardiovasc Diagn 1997; 42: 191–194
Lee KJ, Humpl T, Hashmi A, Nykanen DG, Williams WG, Benson LN.
Restoration of aortopulmonary shunt patency. Am J Cardiol 2001;
88: 325–328
Peuster M, Fink C, Bertram H, Paul T, Hausdorf G. Transcatheter
recanalization and subsequent stent implantation for the treatment
of early postoperative thrombosis of modified Blalock-Taussig shunts
in two children. Cathet Cardiovasc Diagn 1998; 45: 405–408
Bader R, Somerville J, Redington A. Use of self-expanding stents in
stenotic aortopulmonary shunts in adults with complex cyanotic
heart disease. Heart 1999; 82: 27–29
Sivakumar K, Anil SR, Ravichandra M, Natarajan KU, Kamath P,
Krishnakumar R. Emergency transcatheter balloon recanalisation
of acutely thrombosed modified Blalock-Taussig Shunt. Indian Heart
J 2001; 53: 743–748
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Indian Heart J 2004; 56: 677–679
Tandon Prevention of Rheumatic
677
PointFever
of View
Is It Possible to Prevent Rheumatic Fever?
R Tandon
Department of Cardiology, Sitaram Bhartia Institute of Science and Research, New Delhi
R
heumatic fever (RF) and rheumatic heart disease
(RHD) continue to be serious health hazards in most
developing countries including India. RHD has always been
considered to be a preventable disease. The purpose of the
present review is to assess whether RF and RHD can be
prevented. The three strategies for prevention consist of
(i) primordial prevention, (ii) primary prevention, and (iii)
secondary prevention.
Primordial Prevention
Primordial prevention requires, preventing the development of ‘risk factors’ in the community to prevent the
disease in the population and thus protect individuals.
Measures for primordial prevention in relation to RF and
RHD consist of: (i) Improvement in socio-economic status,
(ii) Prevention of overcrowding, (iii) Prevention of undernutrition and malnutrition, (iv) Availability of prompt
medical care, and (v) Public education regarding the risk
of RF from sore throat specially below the age of 15 years.
The last one, that is, public education is the most
important component for primordial prevention. Unless
parents know that a sore throat can cause RF and RHD, it
is most unlikely to be seen by a physician and treated. It is
necessary to point out that the recent resurgence of RF in
United States of America (USA) occurred in well off
families, without any overcrowding and with good quality
medical facilities being readily available. 1 As such,
improvement in socio-economic status and preventing
overcrowding cannot be relied upon to reduce the burden
of RHD. Improvement in socio-economic status is also not
under medical control and it is not possible to wait for it to
happen.
Primary Prevention
Primary prevention of RF is theoretically feasible but
practically almost impossible to achieve at the community
level. However, it can be practised on an individual basis.
Primary prevention requires identification of group-A beta
Correspondence: Dr R Tandon, Sitaram Bhartia Institute of Science
and Research, B-16, Mehrauli Institutional Area, New Delhi 110 016
IHJ-786-04 Point of View.p65
677
hemolytic streptococcal (GABHS) sore throat and use of
penicillin to eradicate the streptococci. Measures for
primary prevention consist of: (i) Public awareness
regarding danger of RF from sore throat, (ii) Identification
of sore throat as being streptococcal, and (iii) Use of
injectable penicillin to cure the streptococcal infection.
It is important to know that oral penicillin may not be
effective in preventing RF. RF occurred in 15% to 48%
children given oral penicillin for 10 days in the recent
epidemic in USA.2-4 It is, therefore, essential that injectable
penicillin is used in order to prevent RF. The recommended
dose of penicillin is 400,000 units of procaine penicillin
twice daily for 10 days. Although recommended, one
injection of 1.2 mega units of benzathine penicillin may
not be enough to eradicate GABHS infection.5
The inability to utilize primary prevention at the
community level is due to the large number of sore throats
required to be treated to prevent RF. Community level
management requires a sledge hammer approach, that is,
treating each sore throat. Bacteriological facilities required
to diagnose streptococcal sore throat at the community
level for the whole country, at present, do not exist and are
not likely in the near future. Hence, each sore throat will
need to be treated. This is logistically not feasible for the
whole country. Anywhere from 3% to 20% of sore throats
can be streptococcal, the rest being viral infections which
do not require treatment. About 0.3% of streptococcal sore
throats result in RF. Recent data suggests that almost 90%
of those who get RF develop RHD.6 Hence if 10,000 sore
throats are treated by the sledge hammer approach,
anywhere between 300 to 2000 streptococcal sore throats
would be required to be treated (assuming that 3-20% of
these are streptococcal). This would result in preventing
RF in 1 to 6 children (0.3% streptococcal sore throats cause
RF), and RHD in 5 or 6 children (Fig. 1). Thus community
level primary prevention is not feasible although it may be
possible for select individual patients.
Another problem with sledge hammer approach is the
identification of sore throat and its treatment. The data
related to resurgence of RF in USA indicates that up to 78%
of streptococcal sore throats may be asymptomatic. The 10day oral penicillin treatment was not followed even by well
educated families and up to 48% of those given oral
2/7/2005, 1:54 PM
Indian Heart J 2004; 56: 677–679
678 Tandon Prevention of Rheumatic Fever
Anti-Streptococcal Vaccine
Fig. 1. Sledge hammer approach is not cost effective.
GABHS : Group-A beta hemolytic streptococcus; RF : rheumatic fever;
RHD : rheumatic heart disease
penicillin still developed RF. 2,4 Unless a sore throat is
symptomatic, it would not be treated and can result in RF.4
This makes primary prevention, based on the diagnosis of
streptococcal sore throat and use of oral penicillin, inadequate to reduce the burden of RHD in the country.
As of today there are no markers which can be utilized
to identify susceptibility to RF.7 Susceptibility to RF in the
form of studies of HLA and the B-lymphocyte antigen,
D8/17 have not given results which can be utilized to
identify the susceptible people in the population to practice
primary prevention.7
However, primary prevention is feasible if an antistreptococcal vaccine becomes available.
Secondary Prevention
Secondary prevention requires identification of those who
have had RF or have RHD. Once identified, the patient needs
injections of benzathine penicillin, given once in two to
three weeks, depending on age, body size and muscle mass.
Benzathine penicillin is painful, and may result in fever and
very rarely (one in a million injections in children) in
anaphylactic reactions. Most physicians are very reluctant
to give benzathine penicillin injections. Penicillin
prophylaxis is considered necessary because RF has a
tendency of recurrence in those who have had RF in the
past. Each new attack causes further damage to the
valvular tissue making the disease worse than before.6
Secondary prevention can reduce the chance of recurrence
but cannot prevent the initial damage. While it is ethically
mandatory to prevent recurrences, secondary prevention
cannot reduce the burden of RHD.
IHJ-786-04 Point of View.p65
678
Availability of an anti-streptococcal vaccine which could
prevent streptococcal infection is essential for primary
prevention of RF. It is at present not available.
Several GABHS protein components and the polysaccharide have been considered for utilization in
developing a vaccine.8 Most work has been done in relation
with the M-protein, considered to be the virulence factor
of the GABHS. M-protein has been found to be strainspecific, that is, each strain has its specific characteristics
and will protect against only that particular strain. Since
more than hundred different strains have been identified it
becomes essential that the vaccine must be polyvalent, that
is, it should incorporate all those strains which are present
in the community. The problem associated with M-protein
is that the GABHS has a strong tendency for mutation
which can occur rapidly.9 A vaccine made from the locally
dominant strains of GABHS may not be effective if the
infection is due to a mutant organism. M-protein has a
conserved C-region component which is common to most
strains and variable A and B regions which differ from strain
to strain. Attempts to use the preserved C-region
component of M-protein have not succeeded as yet.
More recently GABHS has been found not to express
M-protein.10 If fatal infection can occur from GABHS which
does not have M-protein, it is difficult to accept that Mprotein is the main virulence factor of GABHS. Vaccine
based on M-protein is unlikely to succeed because : (i) Mprotein cross-reacts with myocardium and may not be safe,
(ii) M-protein is strain-specific, hence the anti-GABHS
vaccine has to include all the strains in the community, (iii)
since GABHS strains vary from place to place, in a large
country like India, vaccine based on M-protein made in
Delhi may not be effective in Chandigarh, Chennai or
Mumbai, (iv) GABHS mutation alters the emm gene
sequence of the M-protein. Mutation can occur in a few
weeks, making the vaccine ineffective even in a very short
time9 and, (v) virulent GABHS is now known not to express
M-protein. Hence, M-protein cannot be the chief virulence
factor of GABHS.10
Other components of GABHS which are being tried for
preparing a vaccine are GABHS C5a peptidase, a major
surface virulence factor; fibronectin binding protein sfb1,
and the chimeric peptide J8 from the conserved region of
the M-protein.11
Streptococcus pneumoniae (pneumococcus) is another
variety of streptococcus species causing disease in humans.
A vaccine against pneumococcal infection is already
available and is being used though it is, as yet, not as
2/7/2005, 1:54 PM
Indian Heart J 2004; 56: 677–679
effective as one would like it to be. The vaccine has been
prepared using the polysaccharide conjugated with proteins
to make it stable and have a longer duration of effectiveness.
The GABHS polysaccharide has been shown to be
immunologically active and reactive with cardiac valvular
tissue.12 Since the polysaccharide component of GABHS is
uniformly identical, it is surprising that it is not being
utilized to prepare an anti-GABHS vaccine as has been done
for the anti-pneumococcal vaccine.
We are fortunate in our country that the health of the
child generally remains a priority and responsibility of the
parents even when the child becomes an adult. Hence,
prevention of RF and RHD is possible to a large extent if we
can provide the message, in local languages, to the
population (parents) that sore throats should not be
neglected; that sore throats should be shown to a doctor
for treatment to prevent RF and RHD. All India Radio and
Doordarshan are the only means available for reaching
each and every corner of the country and should be utilized
for this purpose. If education can be made compulsory till
the age of 15 years, school health care facilities can be
utilized to control RF.
The answer to the question, “Is it possible to prevent
rheumatic fever?” has to be “No” for primary prevention at
the community level. Primary prevention will have to wait
till a safe and effective GABHS vaccine becomes available.
Acknowledgement
The author wishes to thank Ms Lata Joshi for helping in
the preparation of the manuscript.
IHJ-786-04 Point of View.p65
679
Tandon Prevention of Rheumatic Fever 679
References
1. Veasy LG, Tani LY, Hill HR. Persistence of acute rheumatic fever in
the intermountain area of the United States. J Pediatr 1994; 124:
9–16
2. Congeni B, Rizzo C, Congeni J, Sreenivasan VV. Outbreak of acute
rheumatic fever in northeast Ohio. J Pediatr 1987; 111: 176–179
3. Hosier DM, Craenen JM, Teske DW, Wheller JJ. Resurgence of acute
rheumatic fever. Am J Dis Child 1987; 141: 730–733
4. Veasy LG. Lessons learned from the resurgence of rheumatic fever
in the United States. In : Narula J, Virmani R, Reddy KS, Tandon R
(eds). Rheumatic Fever. Washington : Am Registry of Path 1999,
pp 69–78
5. Dajani A, Taubert K, Ferrieri P, Peter G, Shulman S. Treatment of
acute streptococcal pharyngitis and prevention of rheumatic fever:
a statement for health professionals. Committee on Rheumatic fever,
Endocarditis, and Kawasaki Disease of the Council on Cardiovascular disease in the Young, the American Heart Association.
Pediatrics 1995; 96: 758–764
6. Juneja R, Tandon R. Rheumatic carditis : a reappraisal. Indian Heart
J 2004; 56; 252–255
7. Krishnakumar R, Rammohan R, Narula J, Kaplan EL. Epidemiology
of streptococcal pharyngitis, rheumatic fever and rheumatic heart
disease. In : Narula J, Virmani R, Reddy KS, Tandon R (eds).
Rheumatic Fever. Washington : Am Registry of Path: 1999, p 60
8. Fischetti VA. Vaccine development for Group A streptococcal
Infection. In : Narula J, Virmani R, Reddy KS, Tandon R (eds).
Rheumatic Fever. Washington : Am Registry of Path : 1999,
pp 473–484
9. Kaplan EL, Wotton JT, Johnson DR. Dynamic epidemiology of group
A streptococcus serotypes associated with pharyngitis. Lancet 2001;
358: 1334–1337
10. Bennett-Wood V, Selvaraj G, Goodfellow A, Martin D, Sriprakash
KS, Robins-Browne R, et al. Highly virulent group A streptococci
that appear not to express M protein. (Abstract 05.6) Presented at
the XV Lancefield International Symposium on Streptococci and
Streptococcal Diseases. Goa, India, Oct 2002
11. McMillan DJ, Davies MR, Browning CL, Good MF, Sriprakash KS.
Prospecting for new group A streptococcal vaccine candidates.
Indian J Med Res 2004; 119 (Suppl) : 121–125
12. Gulizia JM, McManus BM. Immuno-pathological studies of
rheumatic fever. In : Narula J, Virmani R, Reddy KS, Tandon R (eds).
Rheumatic Fever. Washington: Am Registry of Path : 1999,
pp 235–244
2/7/2005, 1:54 PM
680 MukhopadhyayImages
et al. Iatrogenic Aortocoronary Arteriovenous Fistula
Cardiovascular
Indian Heart J 2004; 56: 680–681
Iatrogenic Aortocoronary Arteriovenous Fistula
Saibal Mukhopadhyay, Jamal Yusuf, Mohit D Gupta, MP Girish, Vijay Trehan
Department of Cardiology, GB Pant Hospital, New Delhi
Fig. 1. Angiogram showing left internal mammary artery (LIMA,↑↑)
anastomosed to a cardiac vein, which is draining into the coronary sinus
(CS, ↓).
A
60-year-old male patient having undergone coronary
artery bypass surgery (CABG) three months back in
another hospital, presented to us for evaluation of his
persistent symptoms of exertional angina (NYHA class II).
As per the operative records, revascularization had been
performed in all the three major coronary arteries with a
left internal mammary artery (LIMA) bypass to the left
anterior descending artery (LAD) and aortocoronary
saphenous venous grafts to the right coronary artery (RCA)
and the left circumflex artery (LCx). The patient was taken
up for coronary angiography, which showed total occlusion
of proximal LAD, 99% stenosis of LCx continuing as major
obtuse marginal and 90% stenosis of mid RCA with LAD
filling retrogradely from the right system. Angiogram of
the graft vessels showed patent saphenous venous grafts to
LCx and RCA, while angiogram of the LIMA showed that it
was anastomosed distally to a cardiac vein instead of LAD,
Correspondence: Dr Saibal Mukhopadhyay, Senior Research Associate
Room No.126, Academic Block, Department of Cardiology, GB Pant Hospital
New Delhi 110 002. e-mail: [email protected]
IHJ-613-03 Cardiovascular Images.p65
680
which in turn was draining via the coronary sinus into the
right atrium (Fig. 1). A right heart pressure study along
with a full oxygen saturation run was done. Though the
pressures in the right heart chambers and the pulmonary
artery were normal, there was significant step up in oxygen
saturation in the coronary sinus (84%, normal being <
50%) and from right atrium (72%) to pulmonary artery
(80%) with calculated Qp-Qs ratio of 1.5:1. In view of the
patient’s persistent symptoms and a significant left-to-right
shunt, closure of the fistula was decided. He was taken up
for percutaneous revascularization of LAD to be followed
by coil occlusion of the LIMA. However, we failed to cross
the totally occluded LAD, hence the patient was referred
for surgical correction.
Aortocoronary venous fistula caused by inadvertent
grafting of a coronary vein is a rare complication of coronary
artery bypass graft surgery (CABG). The occasional
intramyocardial course and the overlying epicardial fat of
target coronary arteries cause difficulty in identifying the
target coronary arteries resulting in an inadvertent
aortocoronary vein fistula. The natural history of
inadvertent aorto-coronary arterial to coronary vein fistulas
is unknown but bacterial endocarditis, fistula rupture,
myocardial ischemia, and development of significant left-toright shunts with possible congestive heart failure have been
suggested as possible complications similar to that seen in
congenital arteriovenous coronary fistulas.1 Potentiation of
myocardial ischemia is a significant concern in this patient
population, as arterialization of the coronary venous system
without ligation of the vein proximally has not been shown
to result in retrograde perfusion of the myocardium. 2
Further, fistulas of this type also produce myocardial
ischemia by the coronary steal phenomenon.3 While the
traditional therapeutic approach has been surgical closure,4
a growing experience has been reported with transcatheter
embolization of the fistula combined with revascularization
of the originally intended target vessel.1,5,6
References
1. Williams J Thomas, Williams B Moskowitz, Arthur Freedman, George
W Vetrovec, Euelyne Goudreau. Therapeutic embolization of unusual
iatrogenic complications related to coronary revascularization.
Catheter Cardiovasc Interv 1999; 46: 457–462
2/7/2005, 1:55 PM
Indian Heart J 2004; 56: 680–681
Mukhopadhyay et al.
2. Klinke WP, Pepine CJ, Conti CR. Demonstration of an inadvertently
created aortocoronary venous anastomosis: evidence against the
clinical effectiveness of retrograde coronary venous perfusion. Cathet
Cardiovasc Diagn 1979; 5: 367–370
3. Scholz KH, Wiegand V, Rosemeyer P, Chemnitius JM, Kreuzer H.
Aortocoronary artery to coronary vein fistula with potential of
coronary steal as complication of saphenous vein jump bypass graft.
Eur J Cardiothorac Surg 1993; 7: 441–442
4. Calkins JB Jr, Talley JD, Kim NH. Iatrogenic aortocoronary venous
fistula as a complication of coronary artery bypass surgery: patient
report and review of literature. Cathet Cardiovasc Diagn 1996; 37:
55–59
IHJ-613-03 Cardiovascular Images.p65
681
Iatrogenic Aortocoronary Arteriovenous Fistula 681
5. Goldbaum TS, Marsh HB, Maxwell DD. Simultaneous percutaneous
transluminal coronary angioplasty and transcatheter embolization
of iatrogenic aortocoronary vein fistula. Am J Cardiol 1985; 55:
578–580
6. Maier LS, Buchwald AB, Ehlers B, Ruhmkorf K, Scholz KH. Closure
of an iatrogenic aortocoronary arteriovenous fistula: transcatheter
balloon embolization following failed coil embolization and salvage
of coils that migrated into the coronary venous system. Catheter
Cardiovasc Interv 2002; 55: 109–112
2/7/2005, 1:55 PM
682 Letters
to the
Editor
Letters
to the
Editor
Role of Cardiac Magnetic Resonance
Imaging in Identification of Amyloid
Cardiomyopathy
W
e congratulate the authors on their recent comprehensive article on cardiac amyloid.1 The role of
echocardiography in making the diagnosis was discussed
in some detail and it is likely to remain the principal imaging
modality for most patients. In a few cases, however, a limited
acoustic window with poor myocardial visualization
necessitates further investigation. We suggest that there is
a role for cross-sectional techniques such as cardiac
computed tomography (CT) and magnetic resonance
imaging (MRI) in this situation.
Frequently, the principal differential diagnosis other
than amyloid in a patient with features of restrictive
myocardial disease is that of hypertrophic cardiomyopathy.
As the authors point out, the distinction can be difficult on
echocardiography where diffuse myocardial hypertrophy
is the rule in both conditions. Cardiac MRI can enable
differentiation between these pathologies to be made on the
basis of both morphological appearances and signal
intensity characteristics.2
The literature on this topic is sparse but several recent
reports indicate that increase in right or left atrial wall
thickness, or thickening of the interatrial septum in the
Indian Heart J 2004; 56: 682–686
setting of biventricular hypertrophy and depressed
contractility is highly suggestive of cardiac amyloidosis.2,3
Experience at our centre confirms these findings. In the last
few years we have seen several cases of biopsy-proven
cardiac amyloid. In each case the diagnosis was suggested
at MRI on the basis of diffuse left ventricular hypertrophy
(LVH) in association with right atrial wall thickening and/
or nodularity (Fig. 1). Similar findings may also be observed
Fig. 2. Close up from axial contrast-enhanced CT thorax. Infiltration and
nodularity of the right atrial wall is present (arrows). Septal hypertrophy is
also evident (asterisk).
Fig. 1. Axial steady-state free precession image. Note the thickening of the posterior right atrial wall (solid arrow), interatrial septum (dotted arrow) and left
ventricular septum and lateral walls. A small pericardial effusion is present
(asterisk).
IHJ-790-04 Letter-to-Editor.p65
682
Fig. 3. Technetium pyrophosphate scan in a patient with cardiac amyloid. Diffuse uptake of radio-isotope is present throughout the myocardium.
2/7/2005, 1:55 PM
Indian Heart J 2004; 56: 682–686
on CT of the thorax which can be a useful investigation
where facilities for MRI are not available (Fig. 2). Finally,
pyrophosphate scanning should also be considered as
cardiac amyloid often demonstrates diffuse myocardial
uptake with this technique (Fig. 3).4
We thus urge your readers to consider the contribution
that all forms of non-invasive imaging may make, when
pursuing this often-difficult clinical diagnosis.
References
1. Kothari SS, Ramakrishnan S, Bahl VK. Cardiac amyloidosis – an
update. Indian Heart J 2004; 56: 197–203
2. Fattori R, Rocchi G, Celletti F, Bertaccini P, Rapezzi C, Gavelli G.
Contribution of magnetic resonance imaging in the differential
diagnosis of cardiac amyloidosis and symmetric hypertrophic
cardiomyopathy. Am Heart J 1998;136: 824–830
3. Celletti F, Fattori R, Napoli G, Leone O, Rocchi G, Reggiani LB, et al.
Assessment of restrictive cardiomyopathy of amyloid or idiopathic
etiology by magnetic resonance imaging. Am J Cardiol 1999; 83:
798–801
4. Karp K, Naslund U, Backman C, Eriksson P. Technetium-99m pyrophosphate single-photon emission computed tomography of the
heart in familial amyloid polyneuropathy. Int J Cardiol 1987; 14:
365–369
Andrew Crean, Naeem Merchant
Department of Cardiovascular MRI, Toronto General Hospital
Toronto, Ontario, Canada
Letters to the Editor 683
antibiotics. Echocardiographic assessment showed dtransposition of great arteries, small ventricular septal
defect, and restrictive atrial septal defect. The atrial septum
was found to be thick, not amenable to balloon atrial
septostomy. He was taken up for static balloon atrial
dilation. It was impossible to obtain the venous access from
the femoral route probably because of earlier bilateral
saphenous venous cut down done in another center prior
to referral to our institution. We did a percutaneous
cannulation of the right hepatic vein to obtain access for
the procedure. Under general anesthesia, percutaneous
puncture of right hepatic vein was done using a 20 gauge
needle introduced in the right subcostal margin at the
midclavicular line, and the hepatic vein was cannulated
using ultrasound guidance. A 0.025" hydrophilic
guidewire (Terumo Corp, Tokyo, Japan) was introduced into
the right hepatic vein to the inferior vena cava and right
atrium (Fig. 1). The needle was exchanged for a 5 F sheath.
The atrial septum was crossed using a Cournand catheter
and a 0.018" exchange guidewire was placed in the left
upper pulmonary vein through this. The atrial septum was
dilated by a 12 mm × 3 cm Tyshak II balloon (NUMED
Canada Inc.) tracked over the wire (Fig. 2). Echocardiography following the procedure showed a 5 mm
bidirectionally shunting atrial septum defect. Oxygen
saturation improved to 68% following the procedure. At
the end of the procedure the sheath was removed from the
Transhepatic Balloon Dilation of
the Interatrial Septum
B
alloon atrial septostomy is a life-saving procedure in
patients with d-transposition of great arteries who have
inadequate mixing between the systemic and pulmonary
circulations. When the septum is thick, a blade septostomy1
or static balloon dilation of the interatrial septum2 may be
done. These procedures are commonly done through the
femoral venous access. However, in case the femoral
venous access is not available, transhepatic route may be
considered.3,4 A nine-week-old (2.5 kg) infant was referred
to the emergency department with cyanosis since birth
with acute worsening of three days duration. Initial
assessment in the emergency department revealed a deeply
cyanotic infant in shock. Blood gas analysis showed arterial
oxygen saturation of 26% and a pH of 7.24 with a
bicarbonate of 15.5 meq/L. The patient was managed with
bolus infusion of intravenous (IV) fluids, inotropes and
IHJ-790-04 Letter-to-Editor.p65
683
Fig. 1. Anteroposterior view showing the guidewire (white arrow) in the right
atrium introduced transhepatically via the 20 gauge needle (black arrow).
2/7/2005, 1:55 PM
Indian Heart J 2004; 56: 682–686
684 Letters to the Editor
4. Wilson NJ, Culham JA, Sandor GG. Successful treatment of a
nondeflatable balloon atrial septostomy catheter. Pediatr Cardiol
1990; 11: 150–152
5. McLeod KA, Houston AB, Richens T, Wilson N Transhepatic
approach for cardiac catheterisation in children: initial experience.
Heart 1999; 82: 694–696
6. Xiaoming Z, Zhonggao W. Interventional and semi-interventional
treatment for Budd-Chiari syndrome. Chin Med Sci J 2003; 18:
111–115
Shyam S Kothari, S Anandaraja, Ram Prakash,
Balasundaram, Gurpreet S Gulati
Department of Cardiology
All India Institute of Medical Sciences, New Delhi
Fig. 2. Anteroposterior view showing the balloon (white arrow) being inflated
across the atrial septum.
hepatic vein and gelfoam embolization of the liver
parenchyma was done for hemostasis. Ultrasound
examination of the abdomen done subsequently did not
show any perihepatic blood collection or ascites. However,
the patient succumbed to sepsis and multiorgan failure
before definitive repair could be done.
Transhepatic access in children is being increasingly
reported for various diagnostic and interventional
procedures.3-5, The access is obtained by a 22 gauge Cheba
needle3 or by using conventional 20 gauge needle.5 The
failure rates for percutaneous hepatic vein cannulation
reported by these series were 5.5%3 and 17%. 5 Fatalities
have been reported from intraperitoneal bleed, thus it is not
a procedure of choice.6 To the best of our knowledge,
balloon dilation of the atrial septum has not been previously
reported using this access. In conclusion, balloon dilation
of the atrial septum through transhepatic route is feasible
in infants and should be appropriately utilized in the
absence of other venous access.
References
1. Park SC, Neches WH, Zuberbuhler JR, Lenox CC, Mathews RA,
Frucker RJ, Zoltun RA. Clinical use of blade septostomy. Circulation
1978; 58: 600–606
2. Shrivastava S, Radhakrishnan S, Dev V, Singh LS, Rajani M. Balloon
dilatation of atrial septum in complete tansposition of great arteries:
a new technique. Indian Heart J 1987; 39: 298–300
3. Shim D, Lloyd PR, Cho KJ, Moorehead CP, Beekman RH 3rd.
Transhepatic cardiac catheterization in children: evaluation of
efficacy and safety. Circulation 1995; 92: 1526–1530
IHJ-790-04 Letter-to-Editor.p65
684
Lipid Levels and Coronary Heart
Disease: Need for Region-Specific
Guidelines
T
he recent recommendations for the National
Cholesterol Education Program Adult Treatment Panel
(NCEP ATP) III guidelines by Grundy et al.1 do not differ
significantly from the previous version of ATP III. Although
evidence has been mounting on lowering low-density
lipoprotein cholesterol (LDL-c) even in apparently normal
individuals, the ATP III guidelines still stratify LDL-c goals
based on presence of risk factors. It is now known that
screening for conventional risk factors fails to identify more
than 50% of the individuals who will present with acute
coronary syndromes.2 In this context I presume that the
LDL-c goals set by the ATP III may not be able to cover many
patients who may be at risk of coronary heart disease. The
normal range of LDL-c in a newborn is a median value of
100 mg/dl. There is no physiological reason why an adult
should have an acceptable LDL-c of more than 100 mg/dl
irrespective of the presence or absence of risk factors. A
simple goal of keeping LDL-c levels below 100 mg/dl in all
patients will enable more patients to reduce the risk of
coronary artery disease.
In most diseases we tend to follow Western guidelines
due to a lack of such guidelines in developing countries.
South Asia has a vast talent of medical and epidemiological
personnel and is well equipped to form guidelines and
practice recommendations on its own. Moreover the
dietary habits and lipid profile of south Asians differ from
that of Western population. Guidelines can be implemented
by forming a task force among all SAARC countries which
will also augment better regional co-operation.
2/7/2005, 1:55 PM
Indian Heart J 2004; 56: 682–686
Letters to the Editor 685
References
1. Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunnighake
DB, et al. For the Coordinating Committee of the National Cholesterol
Education Program. Implications of recent clinical trials for the
National Cholesterol Education Program Adult Treatment Panel III
guidelines. Circulation 2004; 110: 227–239
2. Benzaquen LR, Yu H, Rifai N. High sensitivity C-reactive protein: an
emerging role in cardiovascular risk assessment. Crit Rev Clin Lab
Sci 2002; 39: 459–497
Vijay R Prabhakar
Clinical Research Physician, Department of Medical Affairs
Taipei, Taiwan
Late Stent Thrombosis Following
Antiplatelet Withdrawal While
Fasting During Holy Months
antiplatelets is relevant to bare metal stents as well. This
complication has been studied extensively with brachytherapy and stenting.3 It is clear that endothelialization is
delayed by brachytherapy and possibly by drug-eluting
stents; however it is still not clear when and whether
endothelialization is absolutely complete with bare metal
stents. Therefore, until such time we have definite data, we
believe that all patients receiving either drug-eluting or bare
metal stents should continue atleast aspirin life-long which
should not be withheld for prolonged periods. It remains to
be decided how long we continue dual antiplatelet therapy.
In this context, there is also the possibility of a greater
rebound increase in platelet activity on withdrawal of both
antiplatelet drugs. Stenting should be avoided in patients
who are likely to be non-compliant, scheduled for major
surgery and those at high risk for late thrombosis. The
absolute need for prolonged and uninterrupted aspirin
therapy for stented patients should be emphasized to
patients, physicians and health care workers across all
religions and societies.
S
erious clinical implications of discontinuing antiplatelet
therapy even many months after drug-eluting stent
implantation have been reported.1,2 We report the case of
a patient who presented with acute myocardial infarction
and angiographic late thrombosis 135 days following bare
metal stent implantation. The patient had discontinued all
medications including dual antiplatelets one week prior to
presentation while observing a religious fast.
A 53-year-old Hindu gentleman admitted to the hospital
in June 2004 had a significant lesion in the left anterior
descending artery. He underwent percutaneous intervention the same week with 2 bare metal stents (3 ×15
mm; DriverTM, Medtronic Galway, Ireland, and 2.5 × 23 mm
Prolink TM , Vascular Concepts Ltd Crawley, UK; both
deployed at 16 atm) being placed in the left anterior
descending artery. He had no further symptoms. He stopped
all medications in October 2004. One week later (135 days
after stenting), he presented with anterior myocardial
infarction. Angiography showed stent occlusion and
extensive thrombus after guidewire passage. Percutaneous
intervention restored vessel patency.
Discontinuation of medications (mainly antiplatelets)
is particularly relevant in Asian countries with large Hindu
and Muslim populations. People of both these faiths observe
several weeks of religious fasting during the holy months
of Navratras and Ramjan respectively. This patient had
discontinued all medications for one week during the
Navratras (nine nights of worship for the Mother Goddess
Durga during the moonlit fortnight).
This report illustrates that discontinuation of
IHJ-790-04 Letter-to-Editor.p65
685
References
1. McFadden EP, Stabile E, Regar E, Cheneau E, Ong AT, Kinnaird T, et
al. Late thrombosis in drug-eluting stents after discontinuation of
antiplatelet therapy. Lancet 2004; 364: 1519–1521
2. Eisenberg MJ. Drug-eluting stents: some bare facts. Lancet 2004; 364:
1466–1467
3. Waksman R, Bhargava B, Mintz GS, Mehran R, Lansky AJ, Satler LF,
et al. Late total occlusion following intracoronary brachytherapy for
patients with instent restenosis. J Am Coll Cardiol 2000; 36: 65–68
Balram Bhargava, Ganesan Karthikeyan, Rakesh Yadav,
Nitish Naik, Gautam Sharma
Department of Cardiology,
All India Institute of Medical Sciences, New Delhi
Angina Pectoris Presenting as
Headache
A
ngina pain has been known to radiate from the chest
to the shoulders, extremities, neck, jaws and teeth.
Anginal equivalents above the mandible and below the
umbilicus are quite rare.1 We report a case of ischemic heart
disease who presented with global headache without chest
pain.
2/7/2005, 1:55 PM
Indian Heart J 2004; 56: 682–686
686 Letters to the Editor
A 66-year-old woman, who was a known hypertensive
and diabetic, came to our emergency department with
complaint of severe episodic headache with uneasiness. Her
pulse rate was 86 beats per min (bpm) and blood pressure
was 130/90 mmHg. She was admitted in medical ward for
observation where her electrocardiogram revealed 1-2 mm
ST segment depression in anterior leads. She underwent
coronary arteriography which revealed 75% stenosis in
proximal left anterior descending artery (LAD). She underwent percutaneous transluminal coronary angioplasty
(PTCA) with stenting to proximal LAD, following which
she was completely asymptomic.
Headache is a rare symptom of myocardial ischemia.2
When present, it is often associated with typical angina. In
our patient headache was the only symptom of myocardial
ischemia. The association of cardiac headache with
coronary artery disease (CAD) has been previously
reported.2-4 Anatomic convergence of cardiac nerve fibers
IHJ-790-04 Letter-to-Editor.p65
686
on central pathway receiving somatic afferent from the
head is likely to be responsible for the perception of cardiac
ischemic pain as headache. It would be worth following up
similar cases to seek a possible explanation for headache
associated with angina, or consider headache as an anginal
equivalent.
References
1. Nagori SB. Global headache in angina pectoris. J Assoc Physicians
India 1992; 40: 212
2. Lanza GA, Sciahbasi A, Sestito A, Maseri A. Angina pectoris: a
headache. Lancet 2000; 356: 998
3. Rambihar VS. Headache angina. Lancet 2001; 357: 72
4. Blacky RA, Rittelmeyer JT, Wallace MR. Headache angina. Am J
Cardiol 1987; 60: 730
Ashok Garg, Pankaj Bohra, MK Gupta
Department of Cardiology, Escort Goyal Heart Centre, Jodhpur
2/7/2005, 1:55 PM
Selected Summaries
687
Selected
Summaries
Indian Heart J 2004; 56: 687–689
Prophylactic Use of an Implantable Cardioverter Defibrillator
after Acute Myocardial Infarction
Hohnloser SH et al. DINAMIT Investigators. N Engl J Med 2004; 351 : 2481-2488
Summary
Comments
Recent trials have shown that prophylactic use of implantable cardioverter defibrillator (ICD) therapy in high
risk patients of ischemic heart disease (IHD), reduced
overall mortality specially in those with compromised
myocardial contractility. These studies dramatically
increased implantation of ICDs worldwide. This is an
expensive form of therapy and raises the question of cost
effectiveness specially if all patients with a prior MI and
significant LV dysfunction are candidates for receiving such
therapy. The Defibrillator IN Acute Myocardial Infarction
Trial (DINAMIT) investigators conducted this randomized,
open label trial in 674 patients who had suffered an MI 640 days prior to randomization (332 patients given ICD
compared with 342 patients receiving optimal medical
therapy). Patients were eligible for enrollment if following
a recent MI, they had a reduced LVEF of ≤ 35% and impaired
cardiac autonomic function in the form of depressed heart
rate variability (a standard deviation of normal-to-normal
RR intervals of ≤ of 70 ms) or an increased average 24-hour
heart rate [≥ 80 beats per min (bpm)] on Holter monitoring.
Criteria for exclusion included congestive heart failure,
revascularization or accepted indications for ICD such as
sustained VT/VF >48 hours after MI. The primary outcome
in this trial was death from any cause. Deaths due to cardiac
arrhythmia were the secondary outcome. During the mean
follow-up of 30±13 months, 120 patients died, 62 in the
ICD group and 52 in the medical therapy group [hazard
ratio: 1.08; p=0.66]. The annual mortality rates were 7.5%
and 6.9% respectively in the two groups. However deaths
due to arrhythmia were less in the ICD group (n=12)
compared with the controls (n=29). The annual rate of
arrhythmic deaths was 1.5% in ICD group compared with
3.5% in controls. This statistically significant decrease in
arrhythmic deaths in the ICD group was however countered
by more deaths from non-arrhythmic causes: 6.1% per year
(n=50) in ICD group versus 3.5% per year (n=29) in the
medical therapy group. Of the 50 non-arrhythmic deaths
in the ICD group the majority (78%) were cardiovascular
in nature. Similarly 79% of deaths in the medical therapy
group were also cardiovascular in nature.
DINAMIT investigators found that prophylactic ICD
implantation, in a high risk subset of patients with recent
MI, did not improve overall survival. However, the ICD
group had a significant reduction in the number of
arrhythmic deaths. In the secondary prophylaxis trials
meta-analysis of the three trials – CID, AVID and CASH
found that ICDs reduced the total mortality rate by 25%
compared to amiodarone (p<0.05). Defining patient
population at a sufficiently high risk for sudden cardiac
death (SCD) and justifying a prophylactic ICD implantation,
has been the focus of many trials. The MADIT-I and II and
MUSTT all favored prophylactic ICD implantation in the
high risk patients of IHD. However, this study has thrown
up results in direct contrast to the previous studies. The
authors have reasoned out the increase in non-arrhythmic
deaths. There was no increase in the complication rate
associated with the implantation procedure. However, the
patients in the DINAMIT study were enrolled early (within
6-40 days) after MI. In comparison the MUSTT and MADIT
trials recruited majority of patients >1 year after the index
MI. In MADIT-II a retrospective analysis revealed that
patients with remote MI (at least 18 months previously)
benefited whereas those with a more recent MI did not
benefit from ICD therapy. This is possibly so because with
the ACE inhibitors and beta blockers, the adverse
ventricular remodeling following MI is prevented or at least
delayed. As the ventricular remodeling that contributes to
electrophysiological disturbances is delayed, it appears
reasonable to expect that the benefits of ICD in preventing
SCD may also be delayed following MI. The other reason
may be that the presence of autonomic dysfunction
identifies patients who have progressive heart failure. So
when the ICD treats the ventricular tachyarrhythmias, the
progressive heart failure continues to notch up mortalities,
thus diluting the ICD advantage. The decrease in SCD is
being offset by an increase in the deaths due to heart failure.
Do the ICD delivered shocks stun the ventricle into overt
failure? In fact, whether cardiac resynchronization therapy
would have improved the outcome is at present not known.
In conclusion, this trial has proved that routine
implantation of ICD in all patients with LV dysfunction
following recent MI cannot be recommended.
IHJ-Selected Sum.p65
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2/7/2005, 1:56 PM
Indian Heart J 2004; 56: 687–689
688 Selected Summaries
Prevention of Lesion Recurrence in Chronic Total Coronary
Occlusions by Paclitaxel Eluting Stents
Werner GS et al. J Am Coll Cardiol 2004; 44:2301-2306
Summary
Comments
This study was undertaken with the aim to assess the safety
and efficacy of paclitaxel eluting stents in chronic total
coronary occlusion (CTO). Polymer-based paclitaxel eluting
stents (Taxus, Boston Scientific Corp., Massachusetts) were
implanted in 48 consecutive patients with a CTO of > 2
weeks duration (median duration 6.3 months). These 48
patients given Taxus stents were compared with a similar
number of patients who received bare metal stents (BMS).
The two groups were matched evenly including history of
diabetes, prior myocardial infarction (MI), lesion site, left
ventricular (LV) function, size of stent and number of stents
deployed. Exclusion criteria was LV aneurysm and TIMI
flow grade <3 after stenting. All patients were followed up
clinically for 12 months and angiography was performed
at 6 months. The primary end point was the one-year
incidence of major adverse cardiac events (MACE) that
included MI, death and target lesion revascularization
(TLR). Secondary end points were the rate of restenosis
[minimal luminal diameter (MLD) <50% of reference
diameter] and incidence of reocclusion. The angioplasty
procedure was performed with the goal of < 20% residual
stenosis within the stent. The strategy was to cover the
occlusion as well as adjacent dissections with one or more
overlapping stents. The mean number of stents were
1.7±0.9 with a mean length of 40±19 mm in Taxus group.
The occlusion length was 17±13 mm whereas the total
length of stent was more than double. This was matching
in the BMS group. The one-year MACE was 12.5% in the
Taxus group and 47.9% in the BMS group (p<0.001),
which was driven by a reduced need for repeat
percutaneous coronary intervention (PCI) or coronary
artery bypass grafting (CABG) (3 v. 21 patients). On
angiography at 6 months, there was 8.3% restenosis in the
Taxus group versus 51.1% in the BMS group (p <0.001).
Moreover the restenosis in the Taxus stents was focal and
successfully treated with repeat PCI with an additional
Taxus stent. The late re-occlusion was seen in 2.1% in Taxus
and 23.4% in BMS group, a reduction of 91%.
Chronic total occlusions are encountered in about a third
of the patients undergoing angiography. Percutaneous
intervention of CTOs accounts for 10-15% of all
angioplasties but the efficacy of BMS is limited with a
significant rate of restenosis (30-50%) and reocclusion (812%). Drug eluting stents (DES) have been proven to be
superior to BMS in the type A lesions. However, there is little
data on the benefit of in the treatment of CTOs. The study
included all patients irrespective of angiographic
characteristics, lesion length, reference vessel diameter etc.
Since long lesions and small vessels (<2.5 mm) were not
excluded and one-third of the patients were diabetic; this
study encompasses what we can call a “real world” type of
experience. This explains the high rate of target vessel
failure (TVF) in BMS group. Despite tackling lesions at
highest risk for failure, the Taxus group showed a reduction
in late loss by 84% as compared with BMS. The TVF in the
Taxus group was unrelated to stent length whereas in the
BMS group, TVF reflected on the length of stent used (38%
in single stent and 71% with ≥2 stents). Similarly, diabetics
had a TVF rate of 64.3% versus 35.3% in the non-diabetics
in BMS group whereas in the Taxus group there was no
significant influence of diabetes on TVF (6.3% v. 9.4%). The
safety profile of Taxus stent was very satisfactory with no
periprocedural MI or subacute stent thrombosis. At the
follow-up angiography, no coronary artery aneurysms was
seen, which has been an area of concern with DES. A recent
study on sirolumus eluting stents (SES) in CTOs by Hoye et
al. showed that the cumulative survival free of MACE was
96.4% in the SES versus 82.8% in the BMS group (p<0.05)
at one year. Restenosis rate at 6 months was 9.1% and only
one case of re-occlusion was seen. The results match those
of the present study. The present study has some limitations
including small number of cases. This was not a double
blind randomized trial but a comparison with matched
controls. The positive results of this study makes it clear
that DES are safe and efficacious in the treatment of CTOs.
The use of DES in CTOs is associated with a reduction in
MACE and restenosis rate compared with BMS.
IHJ-Selected Sum.p65
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2/7/2005, 1:56 PM
Indian Heart J 2004; 56: 687–689
Selected Summaries 689
Amiodarone or Implantable Cardioverter Defibrillator for Congestive Heart Failure
Bardy GH et al. SCD HeFT Investigators. N Engl J Med 2005; 352: 225-237
Summary
Patients with left ventricular (LV) dysfunction are at a high
risk for sudden death. Implantable cardioverter defibrillators (ICDs) have improved survival in patients with
coronary artery disease (CAD) and LV dysfunction as seen
in recent trials. The present trial was conducted to test the
efficacy of treatment with amiodarone versus ICD in high
risk patients who have LV systolic dysfunction secondary
to either ischemic (52%) or non-ischemic causes. The
Sudden Cardiac Death in Heart Failure Trial (SCD HeFT)
investigators randomized 2521 patients with LV ejection
fraction (LVEF) of < 36%, in NYHA class II or III, to either
of the three arms – placebo, amiodarone or ICD therapy.
The placebo and amiodarone were administered in a double
blind fashion. The ICD used was a single chamber ICD
programed to shock only mode (Medtronic). The primary
end point was death from any cause. No dual chamber or
biventricular devices were used and the ICD was programed
to treat sustained ventricular tachyarrhythmias. The three
groups were comparable at baseline as regards the clinical
and demographic characteristics. The median LVEF was
25% with 30% of the patients studied being in NYHA class
III and 70% in class II. The median follow-up was 45.5
months and all surviving patients were being followed for
at least 2 years. Amiodarone was discontinued in 32%
patients and placebo was discontinued in 22%. The adverse
effects associated with amiodarone were chiefly
hypothyroidism (6%) and tremor (4%). ICD implantation
was unsuccessful in 1 patient and 5% of implantations were
associated with complications, defined as clinical events
requiring hospitalization, surgical correction, and
unanticipated drug therapy. An additional 9% of patients
had ICD-related complications later in the course of the
trial; 11% of patients (188) in the drug group received an
ICD subsequently. On follow-up, of the 829 patients in the
ICD group, 259 (31%) had received a shock from the device
with 68% of those shocked having received it for rapid
ventricular tachycardia or fibrillation. The average annual
rate of ICD shocks was 7.5%. There were 244 (29%) deaths
in the placebo group, 240 (28%) in the amiodarone group
and 182 (22%) in the ICD group. There was no difference
in the risk of death in the placebo and amiodarone groups
[hazard ratio (HR) p=0.53], whereas ICD therapy was
associated with a decreased risk of death of 23% (HR: 0.77;
p=0.007). The absolute decrease in mortality was 7.2%
IHJ-Selected Sum.p65
689
points after 5 years in the overall population. In the prespecified subgroups, NYHA class III patients had no
reduction in the risk of deaths with ICD therapy, while there
was 46% reduction in NYHA class II patients.
Comments
This trial has convincingly shown that amiodarone therapy
does not confer a mortality benefit in patients with LV
systolic dysfunction and heart failure. ICD therapy
significantly decreased the relative risk of death by 23%
compared with the conservatively managed patients
(placebo or amiodarone group). This reduction of death was
irrespective of the cause of congestive heart failure (CHF).
It is important to remember that the SCD HeFT investigators
programed the ICDs conservatively with detection above
187 beats per minute (bpm) and ‘shock only’ therapy. In
this trial, anti-tachycardia pacing was not programed and
the back up bradycardia pacing was kept at the lowest value
of 34 bpm. There has been a concern that anti-tachycardia
pacing may do more harm than good because of the
potential for acceleration of the tachycardia rate which may
degenerate into a more dangerous rate or rhythm. Another
concern has been that anti-bradycardia pacing tends to
worsen CHF, therefore the lowest rate was kept so that
pacing was done minimally. By the same reasoning, rate
response pacing was also not allowed. In this study 68% of
shocks were deemed appropriate. There was a high
complication rate of 5% acutely and 9% on follow-up.
Despite this, the benefit is pronounced. Another important
point to emphasize is that all patients with LV dysfunction
irrespective of etiology, benefited from ICD therapy; 30%
of the patients were in NYHA class III and it is surprising
that this trial did not show the same benefit of ICD therapy
in this group as seen for NYHA class II patients. Whether
in this more symptomatic patient subgroup, resynchronization therapy in those with broad QRS and
mechanical dissynchrony be beneficial is for future trials
to explore. There was no benefit with amiodarone therapy
over placebo in NYHA class II patients and 44% decreased
survival in NYHA class III patients. In conclusion, this
trial has shown the benefit of ICD in reducing mortality
in patients with mild to moderate CHF, irrespective of
etiology. This trial has also shown amiodarone to be
ineffective in improving survival, despite optimal
conservative therapy.
2/7/2005, 1:56 PM
Calendar of Conferences/CSI Executive Committee
February 18-20, 2005, International Summit on
CAD and Cardiovascular Interventions, Mumbai
Contact: Dr Satyavan Sharma
Room No. 104, 1st Floor MRC
Bombay Hospital and MRC
12, New Marine Lines
Mumbai 400 020
Tel: 91 22 2205 4532
e-mail: [email protected] and
[email protected]
February 24-27, 2005, 2nd World Congress of Interventional Cardiology, Mumbai
Contact: Dr Lekha Adik Pathak
Memdil, Linking Road
Santacruz (W), Mumbai 400 034
Tel: 91 22 26490262
e-mail: [email protected]
April 1-4, 2005, 2nd International Conference on
Interventional Cardiology, New Delhi
Contact: Dr M Khalilullah, Organizing Secretary
Suite 310, The Heart Centre
2 Ring Road, Lajpat Nagar - IV
New Delhi 110 024
Fax: 2621 7823
Tel: 2643 1179, 2621 7823, 5569 0367,
5569 0370
e-mail: [email protected]
All GB Pant Hospital Alumni are requested to send their
personal details i.e. name, address, telephone numbers
(office and residence) and e-mail address to Prof M
Khalilullah.
Foundation of Cardiovascular Sciences, New Delhi
Invites Applications for Financial Support
Foundation of Cardiovascular Sciences is a non-profit making
trust promoting education and research for young scientists in
the field of cardiovascular medicine and allied sciences. The
foundation provides partial financial support for travel grants
to candidates presenting papers in important International
conferences, or to candidate proceeding on fellowship / higher
training programmes. Candidates are selected by the selection
committee of the trust, whose decision shall be final in all
respects.
Applications giving full bio-data and details of paper to be
presented / grant of fellowship, partial funding from any other
source and other relevant details may be submitted to :
The Managing Trustee
Foundation of Cardiovascular Sciences
41, Uday Park, Khel Gaon Marg, New Delhi - 110049
Cal of Conference.p65
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Indian Heart J 2004; 56: 690
Cardiological Society of India
Executive Committee (2004-2005)
President
P C Manoria, Bhopal
President Elect
A K Kar, Kolkata
Honorary Editor
V K Bahl, New Delhi
Vice Presidents
Amal Kumar Banerjee, Kolkata
J C Mohan, New Delhi
Kajal Ganguly, Kolkata
Honorary General Secretary
P S Banerjee, Kolkata
Treasurer
S S Chatterjee, Kolkata
Honorary Joint Secretary
Sharad Kumar Parashar, Jahandirabad
Soumitra Kumar, Kolkata
Members
Vidhut Kumar Jain, Indore
S K Parashar, New Delhi
K Venugopal, Calicut
Shirish Hiremath, Pune
A K Khan, Kolkata
P K Deb, Kolkata
H K Chopra, New Delhi
H M Mardikar, Nagpur
Shubhendu Banerjee, Kolkata
Binoda Nand Jha, Muzaffarpur
K Sarat Chandra, Hyderabad
Santanu Guha, Kolkata
S B Gupta, Mumbai
Balram Bhargava, New Delhi
Satyendra Tewari, Lucknow
Dhiman Kahali, Kolkata
Rakesh Gupta, New Delhi
C Lakshmikantan, Chennai
A K Maity, Kolkata
Bikash Kumar Chatterjee, Kolkata
B N Shahi, New Delhi
Immediate Past President
R J Manjuran, Tiruvalla
2/7/2005, 1:58 PM