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Journal of the Hoffman
Heart Institute of Connecticut
March 1996- Vol.2 No.1
The Role of Transthoracic and Transesophageal Echocardiography in
the Diagnosis and Evaluation in Patients with Infective Endocarditis
José C. Missri, M.D.
Chief, Section of Cardiology, Medical Director
The Hoffman Heart Institute of Connecticut
Valvular vegetations are the hallmark of infective endocarditis. Although the diagnosis of this
serious clinical entity continues to depend primarily on bedside evaluation and bacteriological
confirmation, echocardiography has assumed a pivotal role in both diagnosis and management of
these patients with endocarditis. With current improvements in instrumentation and the availability
of transesophageal echocardiography (TEE), the technique provides detection of vegetations,
evaluation of location, extent in size of vegetations, and recognition of perivalvular complications
from the infection, such as valve destruction, root abscess and fistula formation. Importantly,
echocardiography also provides accurate evaluation of the severity of valvular regurgitation and
the functional status of the left ventricle.
Detection of Vegetations
Transthoracic echocardiography (TTE) with two-dimensional examination in multiple tomographic
views has been quoted to be between 60-80% sensitive for the detection of vegetations. The
specificity of the technique is fairly high, usually over 90%. Vegetations >3 mm in size are usually
easier to visualize than smaller ones. Likewise, the location of these vegetations may affect their
visualization by echo. For instance, vegetations in a native aortic valve may be easier to detect
than vegetations in a mitral valve. Of importance is the differentiation of active vegetations from
other types of valvular masses. These include: old healed or calcified vegetations, areas of focal
valvular calcification or sclerosis, papillomas in a mitral valve and myxomatous changes in a
mitral valve. This entity can be at times clinically confusing since the motion of a redundant mitral
valve during diastole may produce a "mass-like" appearance with increased thickening of the
valve tissue mimicking a vegetation.
The most difficult vegetations to recognize are those present in a prosthetic valve. The high
ultrasound reflections from the valve itself often makes it impossible to recognize the presence of
any mass attached to the valve. Sometimes, if these vegetations are large enough or if they are
attached to a porcine prosthesis, they can be recognized with routine transthoracic examination.
Detection of prosthetic valve vegetation is perhaps one of the greatest contributions of TEE. In a
study by Jaffe and associates involving 70 patients with documented endocarditis, the authors
found that TTE detected 50 of 58 (68%) vegetations in native endocarditis, as opposed to only 4
of 11 (36%) of prosthetic valve endocarditis. In the subgroup with surgery or autopsy
confirmation, echocardiography was 100% specific. The vegetations that were missed by echo
consisted primarily of small vegetations, vegetations present in calcified native valves or
vegetations involving a prosthetic valve.
Mugge and associates compared transthoracic and transesophageal echo for the detection of
infective endocarditis. In 80 patients with endocarditis involving 91 valves that were proven at
surgery or autopsy, the transthoracic examination showed definite evidence of vegetation in 58%,
possible evidence of vegetation in an additional 19% and no evidence of vegetation in the
remaining 23% of the infective valves. Transesophageal echocardiography on the other hand,
showed definite evidence of vegetation in 82 valves or 90%, again confirming the superiority of
TEE in the group with prosthetic valves. In addition, in the native valves, TEE was 100% sensitive
if one includes the four valves with possible evidence of vegetation. Very similar findings have
been reported by Shiveli and associates in 66 episodes of suspected endocarditis (sensitivity of
TEE, 94%; specificity, 100%). Combining the results of these recent studies, we can conclude
that in native endocarditis TEE is close to 100% sensitive for detection of vegetation. Importantly,
TEE is markedly superior to transthoracic for the detection of vegetation in these patients.
Detection of Complications of Endocarditis
The main clinical complications of endocarditis include embolization, development of severe heart
failure secondary to valvular regurgitation or to myocardial dysfunction, intractable infection
resistant to antibiotic therapy, and ultimately death. With the recent changes in the clinical
spectrum of endocarditis, the increased frequency of intravenous drug abusers, the increased
prevalence of prosthetic valve endocarditis and older age groups, more recent studies
demonstrate less significant differences in the rate of complications among the types of infective
organisms with the exception of Staph aureus, which appears to be associated with a higher
mortality. The severity of valve involvement and degree of regurgitation, the presence of
perivalvular abscesses, the type of valve infected (native versus prosthetic; right side versus left
side) and the size of vegetations are important factors that influence the ultimate clinical course.
In both studies by Jaffe and Mugge, vegetations >10 mm in size were associated with a higher
risk of embolization (26% in Jaffe's studies and 46% in Mugge) than a size <10 mm, (11% in
Jaffe's studies and 19% in Mugge). There has been no significant correlation between the size of
the vegetation and the infective organism or the type of valve infected. Likewise, the size of the
vegetation has related less well with other complications of endocarditis. On the other hand, the
presence of significant valvular regurgitation, perivalvular abscesses or fistulae are all associated
with a greater need for early surgery and, in some studies, with a higher mortality.
Conventional transthoracic examination is very accurate for the evaluation of the severity of
native valvular regurgitation for either the aortic, mitral or tricuspid valves. On the other hand,
prosthetic valve endocarditis, particularly in the mitral position, can be more difficult to evaluate.
This is due to the increased reflections from the prosthesis, which decreases the intensity of the
Doppler ultrasound signal within the left atrium, making it difficult at times to recognize the
presence of a regurgitant jet. Transesophageal echocardiography provides a highly sensitive and
accurate technique for detection of prosthetic valve regurgitation and evaluation of the site of
regurgitation. An important cause of mitral regurgitation in patients with prosthetic aortic valve
endocarditis is a communication between the left ventricular outflow and the left atrium through a
fistulae or through an aortic root abscess that ruptures into the left atrium. Detection of a
perivalvular abscess is possible with transthoracic examination. The sensitivity is higher for
abscess around a native aortic valve. Detection of a perivalvular mitral abscess, however, is more
difficult. Any abscess adjacent to a prosthetic valve is more difficult to recognize. In all of these
entities, TEE has been shown to be more accurate in the recognition of abscess formation.
In summary, echocardiography is currently a highly valuable technique in patients with suspected
or known infective endocarditis. Transthoracic examination should be performed in every patient
suspected of having native valvular disease and the threshold for TEE should be fairly low,
particularly if the transthoracic examination fails to reveal findings of endocarditis and the clinical
picture is highly suggestive of this entity. On the other hand, patient suspected of having a
prosthetic valve endocarditis should routinely undergo a TEE examination because of its
superiority over TTE in detection of vegetations, valvular regurgitation and perivalvular
abscesses. In the absence of pathology in the coronary arteries, the timing and planning of
surgical interventions can be performed accurately with the information provided by
echocardiography.
REFERENCES:
Mugge A, Daniel WG, Frank G, Lichtlen PL. Echocardiography in infective endocarditis:
reassessment of prognostic implications of vegetation size determined by the transthoracic and
the transesophageal approach. J Am Coll Cardiol 1989; 14: 631-638.
Jaffe WM, Morgan DE, Terman AS, Otto CM. Infective endocarditis, 1983-88: Echocardiographic
findings and factors influencing morbidity and mortality. J Am Coll Cardiol 1990; 15: 1227-1233.
Shively BK, Gurule FT, Roldan CA, et al. Diagnostic value of transesophageal compared with
transthoracic echocardiography in infective endocarditis. J Am Coll Cardiol 1991; 18: 391-7.
Daniel WG, Mugge A, Martin RP, et al. Improvement in the diagnosis of abscesses associated
with endocarditis by transesophageal echocardiography. N Engl J Med 1991; 324: 795-800.
The Role of Transthoracic and Transesophageal Echocardiography in
the Diagnosis and Evaluation in Patients with Infective Endocarditis
Bernard Clark, M.D.
Section of Cardiology
The Hoffman Heart Institute of Connecticut
The 42nd Annual Meeting of the American College of Sports Medicine was held in Minneapolis
from May 31 to June 3, 1995. A wide variety of topics of interest to this very diverse group of
scientists were presented, including symposia on molecular biology and disorders of the heart,
outcomes measurements in cardiac rehabilitation and other preventative strategies, and space
medicine. Studies in two areas of preventive cardiology are discussed below. The abstracts may
be found in the May 1995 issue of Medicine and Science in Sports and Exercise, the official
journal of the ACSM.
Physical Activity And Mortality
An inverse relationship between mortality and levels of physical activity have been previously
demonstrated in several populations. A group from the University of Minnesota analyzed data
from the Multiple Risk Factor Intervention Trial (MRFIT) at the 15.8 year of follow-up. Analysis at
two earlier points in the follow-up period (7 and 10.5 years) in this study of 12,138 middle-aged
men at higher risk for developing coronary heart disease revealed a higher death rate from CHD
and all-causes for those in the lowest tertile of leisure-time physical activity. At almost 16 years of
follow-up, the least active tertile continues to have a statistically significant higher mortality rate
than the more active groups, although the gap is narrowing. Of note, the group that had rated
themselves as "much less active than others" had about twice the all-causes mortality rate than
those who had rated themselves as more active. Further analysis of data from this group will be
performed to assess for other factors that may have increased the risk. (MSSE Abstract 323)
While obesity is less prevalent among those who are physically active, there are many who
exercise regularly, but are not thin. Physical activity is prescribed to reduce the risk of
cardiovascular and all-causes mortality. Obese individuals, if active and fit, may accrue these
same benefits from regular exercise. To assess the relationship between physical activity,
mortality, and body composition, the Cooper Institute for Aerobics Research studied a group of
25,389 men (ages 20-88 years of age) for a period of about 8 years and tracked mortality as the
major endpoint. The study group was tested for level of fitness, as well as for body composition.
When divided into three levels of fitness, it was found that the inverse relationship between
fitness and mortality was preserved in the more obese subjects (body mass index > 30 and
between 27 and 30), as well as in the non-obese group (BMI < 27). Multivariate analysis
assessing for the effects of age and coronary risk factors did not alter these findings. (MSSE
Abstract 324)
Lipids And Exercise
Recent studies have demonstrated an increased risk for the development of coronary heart
disease in groups with higher plasma levels of lipoprotein(a). This unique lipoprotein fraction in
found in the upper density range of plasma low density lipoprotein and is usually present in small
quantities. In addition to its atherogenic potential when oxidized, Lp(a) also possesses a prothrombotic effect as the apoprotein has structural similarities to plasminogen. While considerable
data exists on the effects of acute and chronic exercise on levels of total, LDL, and HDL
cholesterol, little exists on the effects of acute and chronic exercise upon Lp(a) levels.
A group from the University of South Carolina presented several abstracts concerning this topic of
interest. To assess the impact of exercise training on Lp(a) levels in premenopausal women, a
group of 26 inactive women were randomly assigned to a control group (no training), a high
intensity training program (at 80% VO2max), and a low intensity training program (at 40%
VO2max). The training groups exercised an average of 3.4 days per week for a 12 week period.
Despite a significant increase in VO2max in trained groups, there were no significant changes in
Lp(a) after training in either exercise group. (MSSE Abstract 384)
The same laboratory studied men who were divided into three activity level groups based upon
their chronic exercise habits. Each cohort was profiled, analyzing for VO2max, plasma cholesterol
levels (total, LDL, and HDL), plasma triglyceride and Lp(a) levels. As expected, the VO2max
values were significantly higher in the moderately active and highly active groups when compared
to the low activity group. Plasma HDL was significantly higher in the most active versus the other
groups (58 mg% vs. 45 mg% for moderately active and 41 mg% for inactive). Plasma triglyceride
levels were significantly lower for both "active" subjects when compared to the inactive subjects.
There were no significant differences for either plasma LDL or Lp(a) between the groups. (MSSE
Abstract 385)
Another study was performed to assess for acute changes in Lp(a) after a single 30-minute bout
of low and high intensity exercise. A group of 12 physically active men were randomized to either
a low (50% of VO2max) or high (80% of VO2max) intensity bout of exercise. The study was again
repeated at the other intensity level. Plasma total cholesterol, triglycerides and Lp(a) levels were
determined before and immediately after exercise. There were no significant differences between
the pre- and post-exercise lipid values at either work intensity. (MSSE Abstract 386)
Practice Guidelines: The Changing Face of Cardiac Rehabilitation
Richard Soucier, M.D.
Fellow in Cardiology, University of Connecticut Health Center
An expert panel convened by the Agency for Health Care Policy and Research and the National
Heart, Lung, and Blood Institute was given the charge to assess the clinical efficacy and costeffectiveness of cardiac rehabilitation. In October 1995, the Clinical Practice Guideline for Cardiac
Rehabilitation was published by the Department of Health and Human Services and is available
in several formats for clinicians, administrators and patients.(1) In addition to documenting the
benefits of program participation, a number of shortcomings of the "traditional" cardiac
rehabilitation program were demonstrated. Prominent among these is the lack of availability for
patients who are unable to attend sessions at a hospital or free-standing site because of location,
lack of transportation, or financial considerations. Furthermore, the focus of traditional programs
has been on a limited scope of cardiac disorders. A majority of participants have recently
experienced a myocardial infarction and/or surgical revascularization. Many patients with
symptomatic coronary disease, non-surgical revascularization, or congestive heart failure are not
considered for recruitment into programs despite potential benefit in these populations.
Background
The benefit of cardiac rehabilitation for patients with coronary artery disease has been well
established. It has been demonstrated, however, that this service tends to be underutilized. In
fact, studies have shown that only 11-20% of appropriate candidates for cardiac rehabilitation are
actually referred. This is compared with a 38% referral rate for patients enrolled in the GUSTO
trials.(1) Among the benefits of participation in these programs are an increase in exercise
tolerance, decrease in symptoms of both angina and CHF, favorable changes in lipid profiles,
decrease in tobacco use, increase in a sense of well-being, and a decrease in mortality.(1)
The favorable effects of rehabilitation occur without significant risk to the patient. In a recent
study, it was demonstrated that post-myocardial infarction patients participating in exercise
rehabilitation had no increase in early post-MI events when compared to non-participants. In over
1,600,000 patient-hours, there were 50 cardiac arrests and 7 myocardial infarctions. There were
8 fatalities in the former group and 2 in the latter. This corresponds to 1 fatal occurrence in over
116,000 patient-hours, similar to the occurrence rate in the general post-MI population.(2) In
another group of 167 randomly selected cardiac rehabilitation programs, the event rates per
1,000,000 patient-hours were 8.9 cardiac arrests, 3.4 myocardial infarctions, and 1.3 fatalities.(3)
Additionally, there is a cost benefit to enrolling patients in adequate cardiac rehabilitation
programs. Perk and Hedback, in a five-year follow up study, compared a group of 147
nonselected post-MI patients less than 65 years of age to 158 age-matched controls who were
not involved in a rehabilitation program. They demonstrated that the cost of the program itself
was offset by the increased tendency for the control patients to be readmitted to the hospital for
recurrent cardiac problems. This, coupled with the fact that patients in cardiac rehab tended to
return to work earlier and more often than controls suggested that enrollment was the costeffective approach to post-MI care.(4) In a non-randomized study of 580 patients having either a
recent MI or CABG, the participants were given the opportunity to participate in a supervised 12
week program of exercise. The subjects exercised to 70-85% of their peak heart rate attained on
a graded exercise test for 1 hour per day, 3 days per week. Due to study design, there were
some differences in baseline characteristics between the 230 participants and the remaining who
declined participation. It was of interest to note that the group taking part in the exercise program
incurred, per capita, an average of $739 lower rehospitalization costs. (5)
Benefits of cardiac rehabilitation have also been demonstrated in selected groups of cardiac
patients, including those with "high" baseline exercise tolerance. Although the relative
improvement in exercise capacity in those patients who were able to exercise to 6 METS was not
as great as those with less capacity, the changes noted in their lipid values were more
favorable.(6) The results of studies of women and cardiac rehabilitation have revealed that
participants have a 20-25% reduction in cardiovascular and all-cause mortality, a decrease in
resting blood pressure, decreased weight, and a favorable change in lipid profiles. Also shown,
however, is a lower referral rate of women to programs and a significantly higher dropout rate.(7)
The impact upon providers of services
The Clinical Practice Guidelines will challenge the flexibility and creativity of those providing
cardiac rehabilitation services. The traditional four-phase program had been designed around
predictable hospital lengths of stay, standard methods of risk stratification, and third party
reimbursement for services that often dictated the length of time a participant spent in
rehabilitation. Rapid changes in the diagnosis and treatment of cardiac disorders have already
altered the landscape considerably and threaten to make the programs of the 1980's and early
1990's old-fashioned if not obsolete.
While there are distinct advantages to having on-site group exercise and educational classes
(social support, staff efficiency), a bulk of the population at risk will not find their way into this
setting. Innovative approaches, including home- or community-based programs will allow a
broader participation and fulfill the mission of providing meaningful secondary prevention to this
large constituency. Bringing education into the home will involve the cooperation of cardiac
rehabilitation professionals and home care agencies, as well as the development of unique and
stimulating teaching materials. The initiation of exercise training at home may be helpful in
encouraging a life-long commitment to increased physical activity, but requires careful risk
stratification and exercise prescription. Trans-telephonic rhythm monitoring will have a role in the
management of selected patients involved in home-based exercise training, particularly those at
moderate risk for exercise.
Programs depending upon "reliable" insurance reimbursement for services will be profoundly
affected by the continued movement away from indemnity coverage to managed care and
capitation. Institutional reimbursement for cardiovascular diagnosis-related groups will
undoubtedly include a component for post-hospitalization care - including cardiac rehabilitation. It
will be the responsibility of the service provider to implement a program that is both efficient and
effective. Diligent tracking of outcomes will be as important during this phase of therapy as during
acute hospitalization.
The Hoffman Heart Institute Experience
Saint Francis Hospital and Medical Center established the first cardiac rehabilitation program in
Hartford in 1976. Initially, a hospital-based training and maintenance phase program was
established with primarily a low to moderate risk population. Separate convalescent phase and
training programs were developed in the mid-1980's as more "high risk" patients were referred.
The Mount Sinai Hospital program established an on-site convalescent phase program and a
busy training and maintenance phase program at the Greater Hartford Jewish Community Center.
Affiliation of the two institutions fostered close cooperation between the cardiac rehabilitation
services and the development of a single program represented both on the hospital campus and
at the GHJCC.
Growth of the traditional outpatient program has been strong, with over 8,000 patient-hours of
participation in fiscal year 1995. However, outcomes data demonstrate that a majority of patients
having myocardial infarction or revascularization do not follow through with outpatient
rehabilitation. Efforts to increase the participation in program of secondary prevention are being
redoubled. Linkage between the inpatient critical pathways and outpatient care plans will help to
ensure continuity of care, including post-discharge education and exercise rehabilitation. This will
also provide flexibility as lengths of stay continue to change. An upgrade of the monitoring and
data management system provide the capability for trans-telephonic voice and ECG monitoring,
facilitating continued contact between discharged patients and the cardiac rehabilitation staff. It is
clear that the new practice guidelines provide not only challenges, but opportunities to those
willing to consider innovative approaches to rehabilitating and educating the patient with heart
disease.
I wish to acknowledge the assistance of Dr. Bernard Clark in the preparation of this manuscript.
REFERENCES
1. Wenger NK, et al. Cardiac Rehabilitation: Clinical Practice Guidelines. AHCPR No. 960672. October 1995.
2. Haskell, WA. Cardiovascular complications during exercise training of cardiac patients.
Circulation 1978; 57:920-4.
3. Van Camp, SP, et al. Cardiovascular complications of outpatient cardiac rehabilitation
programs. JAMA 1986; 256:1160-3.
4. Perk, LJ and Hedback, B. Cardiac rehabilitation - a cost analysis. J of Int Med 1991;
230:427-34.
5. Ades, PA et al. Cardiac rehabilitation participation predicts lower rehospitalization costs.
Am Heart J 1992;123:916-21.
6. Lavie, CJ and Milani, RV. Patients with high baseline exercise capacity benefit from
cardiac rehabilitation and exercise training programs. Am Heart J 1994;128:1105-9.
7. Caras, DS and Wenger NK. Exercise rehabilitation of women with coronary heart
disease. J of Myocardial Ischemia 1993;5:42-52.
Expanding the Indications for Coronary Stenting: Need for Controlled
Clinical Trials
José C. Missri, M.D.
Chief, Section of Cardiology, Medical Director
The Hoffman Heart Institute of Connecticut
Two balloon expandable stents had been approved by the FDA for use in selected situations in
treating coronary artery disease - the Ginturco-Roubin (Cook, Inc.) in 1993 and in 1994, the
Palmaz-Schatz stent (Johnson & Johnson Interventional Systems). However, there has been an
increase in the use of stents beyond their approved indications and this should be a cause for
some concern to the interventional cardiologist. Furthermore, the increase in use of stents is not
presently reimbursed by third party payers or Medicare and is putting significant strain in cardiac
catheterization budgets.
The concept of intravascular stenting was introduced even before Gruentzig's description of nonsurgical balloon recanalization of obstructed coronary arteries in 1977. In 1964, Dotter advocated
the use of "splints" to preserve the luminal patency in the peripheral circulation. Metallic coronary
stents were introduced in the late 1980's for use in the coronary circulation to overcome the two
major limitations of balloon angioplasty: acute vessel closure, which complicates up to 10% of
procedures and restenosis, which continues to limit long-term patency in 30% to 50% of patients.
The Ginturco-Roubin coil stent was approved for treating actual or threatened abrupt vessel
closure because early clinical data showed that it could be deployed successfully in more than
95% of patients when used in an emergency setting for abrupt or threatened vessel closure.
Despite the relatively high rate of in-hospital complications following emergent stenting, the
results with this stent compared favorably to the alternative remedy of emergency bypass
surgery, and therefore the approval of the Ginturco-Roubin stent provided an important tool for
the interventional cardiologist.
The Palmaz-Schatz slotted tubular stent was approved for elective use in patients with new,
discrete lesions in large native coronary vessels. The approval of this device was based on the
two randomized trials, STRESS (Stent Restenosis Study) and BENESTENT (BelgiumNetherlands Stent Trial), which demonstrated that coronary stents offered the first technique for
reduction of angiographic restenosis.
But throughout the country, both these stents are being implanted for non-approved indications.
Specifically, stents are being used in the treatment of restenotic lesions, saphenous vein graft
stenosis and long lesions requiring more than one stent, and in the post-infarction patient despite
the concern for stent thrombosis.
The interventional cardiologist may be induced to implant these devices because of the aesthetic
appeal of the angiographic result associated with stent placement. However, the quality of the
initial angiographic result may not translate into improved clinical benefit in some patient subsets.
In addition to the use of the stent in these situations, the post-implantation anticoagulation
recommendations are not being followed. For example, ticlopidine and aspirin are being
substituted for Coumadin.
This is not to say that the use of stents for off-label indications and variation in the anticoagulation
regimen is being done haphazardly. There are extensive preliminary data to suggest that stents
will be useful for all of the above stated indications, although well-controlled studies need to be
completed.
Proponents of stenting for off-label indications note that the introduction of high pressure balloons
have allowed for better stent implantation. In the past, balloons used for implantation were very
compliant and the stent struts weren't being fully deployed against the vessel wall. Struts were
sticking into the blood stream and may have been the cause for the relatively high thrombosis
rate of 3% to 5% associated with elective stent placement. The problem is that we still do not
know if this change in technical deployment of stents, which is associated with a greater
barotrauma to the vessel wall, may in fact negate the lower restenosis observed with stents.
Ongoing studies must be completed to truly answer this question.
It may be that the use of stents for certain off-label indications will prove efficacious and costeffective while improving long-term outcomes. But assumed success based on widespread use
does not equate to good medicine and is not in the long-term best interests of interventional
cardiologists and their patients. Until well-controlled clinical trials are completed demonstrating
improved efficacy of stenting over other treatment modalities in these expanded patient
populations, stents should be used judiciously.