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Since their development, calcium channel blocking agents have stimulated interest in their potential benefit for a variety of cardiovascular disorders, including heart failure. The rationale for the potential benefit of calcium channel blockers in heart failure is multi-factorial, including vasodilation, correction of perturbed diastolic relaxation, anti-ischemic action, and potential for inhibiting myocyte hypertrophy and injury. Despite these potential benefits, the degree of salutary influence has remained controversial, and a number of studies have suggested potential adverse action in patients with heart failure, perhaps linked to either negative inotropic action or to reflex neurohormonal activation. Diversity among different agents, particularly with regard to tissue selectivity and pharmacokinetics may imply substantial differences in the relative benefits and risks in various subgroups of patients with heart failure. One trial with the newer dihydropyridine agent, amlodipine, indicates benefit to survival in patients with moderate to severe heart failure and reduced ejection fraction. The reproducibility of this finding and the mechanism for this benefit deserves further investigation.

Background: Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials., Methods and Results: We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction < or = 0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n = 145) or carvedilol (n = 133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P = .014) or by a global assessment of progress judged either by the patient (P = .002) or by the physician (P < .001). In addition, treatment with carvedilol was associated with a significant increase in ejection fraction (P < .001) and a significant decrease in the combined risk of morbidity and mortality (P = .029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure., Conclusions: These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.

To assess the hepatic uptake of thallium-201 after exercise treadmill testing and to investigate whether hepatic uptake of thallium-201 may be a useful marker of right coronary artery (RCA) disease, 43 patients were studied: 17 with RCA disease (9 with 1-vessel disease, 8 with multivessel disease including the RCA), 8 with left coronary system disease alone, and 18 with a low probability (< 5%) of coronary disease. All subjects were studied with symptom-limited exercise and redistribution thallium-201 single-photon emission computed tomographic (SPECT) scintigraphy. Two indexes of hepatic uptake were derived: a liver-to-heart ratio after stress, and a stress-to-rest hepatic ratio. The low-probability group had a liver/heart ratio of 0.48 +/- 0.02. In the group with RCA disease alone, liver/heart ratio was 1.29 +/- 0.20 (p < 0.005 vs low-probability group). Patients with multivessel coronary artery disease involving the RCA had a ratio of 1.19 +/- 0.16 (p < 0.005 vs low-probability group), and patients with only left coronary system disease had a liver/heart ratio of 0.87 +/- 0.15 (p < 0.05 vs low-probability group). The stress/rest ratio of the low-probability group was 0.83 +/- 0.04. Patients with RCA disease alone had a stress/rest ratio of 1.49 +/- 0.25 (p < 0.05 vs low-probability group), and patients with multivessel disease involving the RCA had a stress/rest ratio of 1.16 +/- 0.08 (p < 0.005 vs low-probability group).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac toxicity and hemodynamic alterations are frequently associated with high-dose interleukin-2 (IL-2) immunotherapy in cancer patients. Serious cardiac events including myocardial infarction, ischemia, and noninfectious myocarditis have been observed. We document two cases of unusually severe but reversible cardiac abnormalities related to IL-2 therapy: one patient with a profound form of global myocardial hypocontractility and a second patient with regional aneurysmal and dyskinetic changes of the left ventricle. These cases exhibit unique features not previously described in IL-2-treated patients. The possible pathophysiologic mechanisms underlying these global and regional forms of cardiomyopathy, including the production of secondary-messenger molecules such as nitric oxide and myocardial stunning, are discussed. Both patients remain disease free of their cancer (> 3 years since completing therapy), are without residual cardiac dysfunction or recurrent related symptoms, and have not experienced any additional cardiac events. The report demonstrates the complexity of the cardiac toxicities associated with IL-2-based immunotherapy and recognizes a need for treating physicians to be familiar with their management.

Objectives: The aim of this study was to determine whether persistent coronary aneurysms in patients with Kawasaki disease are associated with altered myocardial perfusion and function., Background: Some patients with Kawasaki disease have died suddenly because of severe coronary artery stenosis; others have chronic coronary aneurysms., Methods: Eleven patients with chronic coronary aneurysms were enrolled in the study. The size of the aneurysms and the degree of associated stenosis were determined by angiography in nine patients and by echocardiography in two. All patients underwent simultaneous function and myocardial perfusion assessment during symptom-limited exercise by echocardiography and technetium-99m sestamibi imaging, respectively., Results: Of 33 vascular territories, 18 contained coronary aneurysms measuring 3.5 to 10 mm. Three aneurysms were associated with significant stenosis as detected by angiography. Of the 18 vascular territories, 13 were normal, and 5 manifested stress-induced perfusion defects; of the latter 5 areas, 4 had associated wall motion abnormalities. The three territories supplied by stenotic coronary arteries had both abnormal regional function and perfusion demonstrated during exercise., Conclusions: Patients with chronic coronary aneurysms may have associated stenosis, as detected by angiography, with a subjacent myocardium that is subject to abnormal perfusion and function. However, the majority of coronary aneurysms are associated with normal regional coronary flow reserve, as assessed by myocardial perfusion imaging, and even giant coronary aneurysms may be associated with normal coronary flow reserve and preserved regional myocardial function during stress.

During the past decade progress in the field of myocardial perfusion imaging has resulted in a myriad of choices for perfusion imaging protocols, including choices in types of stressor, imaging modality, perfusion tracer, method of analysis, and a wide range of choices of imaging protocols. This review will examine this latter aspect in the context of choices of perfusion tracers that are now available for wide use. Manipulations of thallium protocols have revolved primarily around optimizing identification of stress defect reversibility and regional myocardial viability. The high image quality and long retention time afforded by the technetium-labeled agents allow the potential for streamlining imaging protocols to maximize efficiency and cost-effectiveness, such as performing stress only imaging in a subset of patients and performing simultaneous assessment of perfusion and function.

Background: The availability of clinical information often influences the interpretation of diagnostic imaging information., Methods and Results: In this study we examined the impact of such data on interpretation of exercise thallium scans and the differences in analysis of such information between radiologists and clinicians. Two hundred thirty-seven exercise tolerance test-thallium scans (122 in patients with suspected coronary disease and 115 in patients with documented coronary disease) were read prospectively, first without and then with the knowledge of clinical information. Test scores, the readers' and clinicians' interpretations of historic data, and any changes in readings or interpretation of scintigraphic data were recorded. We found that the addition of clinical information resulted in changes in interpretation of 63 test results (27%), 20 (8%) of them major. Furthermore, clinical data significantly affected final test scores in 26 patients (11%), potentially affecting clinical management in this group. The changes in test scores were triggered predominantly by differences in interpretation of perfusion abnormalities rather than thallium lung uptake or left ventricular dilation with exercise. The impact of clinical data on overall test scores was greater in patients with suspected than documented coronary disease (p < 0.05). There was good agreement in assessment of clinical information between scan readers and a clinician in tests done in patients with suspected coronary artery disease but not in patients with known coronary disease., Conclusions: We conclude that clinical information has major influences on the interpretation of thallium scans, and interpretation of data can vary significantly between cardiologists and radiologists depending on the nature of the clinical data.

Background: Regional 201Tl activity after resting injection, imaged early and after redistribution, reflects viable myocardium and can predict improved isotope uptake as well as regional and global ventricular function after revascularization. 99mTc-sestamibi, a perfusion tracer with favorable imaging characteristics, has distinct kinetics compared with 201Tl, demonstrating minimal redistribution; this property may give 201Tl an advantage for detecting viable myocardium, particularly in segments with resting hypoperfusion. The purpose of this study was to compare regional activities of 201Tl and 99mTc-sestamibi after resting injections in patients with coronary artery disease and regional or global left ventricular dysfunction and to assess their comparative abilities for predicting recovery of severe regional ventricular dysfunction after revascularization., Methods and Results: Qualitative and quantitative comparisons of rest and redistribution 201Tl activity and sestamibi activity 1 hour after rest injection were performed in 31 patients with coronary artery disease and left ventricular dysfunction. Quantitative analysis of three short-axis tomograms per patient was performed by use of circumferential profiles that allowed analysis of 12 segments per patient. Two-dimensional echocardiography was used to assess wall motion and thickening in segments corresponding to the single photon emission computed tomography data. Concordance between regional 201Tl activity at redistribution imaging and regional sestamibi activity by semiquantitative visual analysis demonstrated concordant regional activity in 87% of segments; among discordant segments, no significant skew was seen, indicating enhanced uptake of one agent over the other. Quantitative analysis for all segments showed significant correlation (r = .86, P < .001) between quantitative regional 201Tl redistribution activity and 1-hour post-rest injection sestamibi activity in individual segments. Eighteen of these patients were revascularized, and echocardiography was repeated 20 +/- 16 days later; segments exhibiting significant regional ventricular dysfunction before revascularization were classified as having reversible or irreversible dysfunction on the basis of the change in wall motion and thickening. 201Tl and sestamibi regional activities were similar in those segments with reversible (72 +/- 11% [percent of peak activity] versus 75 +/- 9%, respectively, P = NS) as well as irreversible ventricular dysfunction (51 +/- 11% versus 50 +/- 8%, P = NS). Positive (75% versus 80% for 201Tl and sestamibi, respectively) and negative (92% versus 96%, respectively) predictive values for recovery of regional ventricular dysfunction after revascularization were similar for the two agents., Conclusions: In patients with coronary artery disease and left ventricular dysfunction, quantified sestamibi activity 1 hour after rest injection parallels redistribution 201Tl activity after a resting injection, suggesting that uptake and subsequent handling of sestamibi are more complex than can be explained by a pure flow tracer with no redistribution. Quantitative analysis of regional activities of both 201Tl and sestamibi after resting injections can differentiate viable from nonviable myocardium, and the two agents comparably predict reversibility of significant regional wall motion abnormalities after revascularization in such patients to a similar degree.

Purpose: The approach to cardiac risk stratification of patients undergoing vascular surgery continues to be controversial. The success of algorithms that use clinical risk factors to determine cardiac risk have been inconsistent. Dipyridamole myocardial scintigraphy (DMS) has been accepted as a sensitive, noninvasive approach to risk stratification with excellent negative predictive value. Low positive predictive value (PPV) of abnormal DMS scans is a shortcoming that contributes to extensive preoperative cardiac evaluation and intervention with associated morbidity, mortality, and cost in most patients who undergo uncomplicated vascular procedures, regardless of DMS results., Methods: Over 6 years, 237 patients underwent DMS before surgical management of infrarenal aortic aneurysm, aortoiliac, or infrainguinal occlusive disease. The value of multiple clinical factors and DMS were assessed retrospectively for the prediction of perioperative myocardial infarction (MI), heart-related death, or preoperative selection for myocardial revascularization. Only congestive heart failure and two or more reversible defects on DMS were statistically significant on logistic regression analysis., Results: The PPV of DMS was 19% for all patients with reversible defects, 12% for patients with one reversible defect, and 36.7% for patients with two or more reversible defects. The rates of cardiac death and MI were 1.3% and 5.9%, respectively. Perioperative echocardiography revealed unchanged postinfarction ejection fraction in most patients who experienced MI. Cost-effectiveness of DMS screening was evaluated., Conclusions: The costs per MI and cardiac death averted suggest a decline in cost-effectiveness of screening with DMS over time, assuming improving cardioprotective strategies of patient care. Clinical risk factors were minimally useful in the prediction of perioperative MI, heart-related death, or need for myocardial revascularization. The PPV of DMS is low, and the majority of MIs may be clinically insignificant. The cost-effectiveness of cardiac screening with DMS may not be justifiable given current trends of health care reform.

Background: Peak dP/dt is a good index of ventricular performance that is not influenced by afterload, wall motion abnormalities, or the variations in ventricular anatomy and morphology commonly encountered among patients with congenital heart disease. Unfortunately, the clinical utility of peak dP/dt has been limited by the fact that its measurement generally requires an intraventricular catheter. However, peak dP/dt occurs during isovolumetric contraction, and the pressure rise during isovolumetric contraction is almost linear. Therefore, the mean dP/dt during isovolumetric contraction (mean dP/dtic), ie, the ratio of the rise in pressure during isovolumetric contraction (aortic diastolic pressure minus the systemic ventricular end-diastolic pressure [VEDP]) over the isovolumetric contraction time, should provide a good estimate of peak dP/dt that could be generated noninvasively., Methods and Results: Echo/phonocardiography was used to measure the isovolumetric contraction time and a blood pressure cuff to estimate aortic diastolic pressure of 27 patients (age, 1 day to 77 years) with congenital or acquired heart disease. VEDP was determined by three methods: (1) intraventricular catheter, (2) assumed VEDP of 10 mm Hg, and (3) assignment of a normal or elevated value on the basis of clinical history. The three estimates of mean dP/dtic thus generated were compared with simultaneous measurements of peak dP/dt obtained during cardiac catheterization. Invasively measured peak dP/dt correlated well with the indirect determinations (r = .95, .89, and .92 for methods 1, 2, and 3, respectively; P < .0001)., Conclusions: Echo/phonocardiography can be used in conjunction with a blood pressure cuff and indirect estimates of VEDP to generate mean dP/dtic, an index of ventricular function that approximates and closely correlates with peak dP/dt. This noninvasive measurement can be obtained in almost any patient and may be useful in the assessment of ventricular performance in a variety of cardiovascular disorders.

Background: Patients with heart failure and reduced left ventricular (LV) ejection fraction (EF) manifest progressive LV dilatation, which is prevented by angiotensin converting enzyme (ACE) inhibitors. In patients with asymptomatic LV systolic dysfunction, in whom there is less activation of the renin-angiotensin system, ventricular remodeling might be less rapid and the benefit of ACE inhibitors less discernible., Methods and Results: One hundred eight patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial, with left ventricular ejection fraction < or = 0.35 but without clinical heart failure, underwent radionuclide ventriculograms, and 49 underwent left heart catheterizations. Measurements were made before and after double-blinded randomization to enalapril (2.5 to 20 mg/d) or placebo. Repeated-measures analysis of all time points showed significant differences for change in end-diastolic volume (EDV) between enalapril and placebo groups. Significant difference between the enalapril and placebo groups (P < .05) was present for change in EDV at 1 year within the catheterization study and at a mean of 25 months within the radionuclide study. Radionuclide EDV increased in placebo patients (119 +/- 28 to 124 +/- 33 mL/m2, mean +/- SD) and decreased in enalapril patients (120 +/- 25 to 113 +/- 25 mL/m2). Differences between the two groups were significantly less than previously described in patients with symptomatic heart failure (P < .02), with less increase in LV volumes in the placebo group and less decrease in volumes in the enalapril group., Conclusions: Chronic ACE inhibitor treatment slows or reverses LV dilatation in patients with asymptomatic LV systolic dysfunction. Compared with symptomatic patients, asymptomatic patients manifest a slower rate of spontaneous LV dilatation and less reduction in LV volumes by enalapril.

To assess the long-term changes in cardiac function in asymptomatic patients with severe left ventricular dysfunction, left ventricular (cineangiography) and right ventricular (radionuclide angiography) function were assessed at baseline in 49 patients enrolled in the prevention arm of the Studies of Left Ventricular Dysfunction. After an average follow-up period of 12.4 months, 30 patients (11 randomized to the placebo group and 19 to the enalapril group) could be restudied to assess the progression of ventricular dysfunction. After 1 year of follow-up, the changes in heart rate, left ventricular end-diastolic and systolic pressure and right ventricular volumes were comparable in both groups. However, there were modest but opposite changes in left ventricular end-diastolic volume (+9 ml/m2 with placebo vs. -10 ml/m2 with enalapril, p < 0.05) and end-systolic volume (+5 ml/m2 with placebo vs. -13 ml/m2 with enalapril, p < 0.05). Mean systolic wall stress increased insignificantly in both groups, whereas ejection fraction increased from 29% to 31% in the placebo group and from 28% to 32% with enalapril (p = NS, placebo vs. enalapril). Even in asymptomatic patients with severe left ventricular dysfunction, there was a slow progression of left ventricular dilation. Enalapril administration appeared to slow this progression, but wall stress was not normalized by the treatment at the doses used in the study, indicating that at least one of the stimuli for further remodeling remained present.

Objective: To define the mechanisms underlying left ventricular diastolic dysfunction in patients with congestive heart failure and normal systolic function and to identify the patients at risk for this syndrome., Study Selection: Studies were selected that describe the clinical observations of congestive heart failure with normal systolic function and that provide experimental and clinical insights into the mechanisms responsible for ventricular diastolic dysfunction., Data Synthesis: Recent studies indicate that a large number of patients (up to 40% in some series) presenting with congestive heart failure have preserved left ventricular systolic function. The factors contributing to altered left ventricular diastolic function include fibrosis, hypertrophy, ischemia, and increased afterload. The latter three factors, alone or in combination, predispose to impaired left ventricular relaxation, an active energy-requiring process. Thus, decreased left ventricular diastolic distensibility (increased diastolic pressure at any level of diastolic volume) may arise not only from altered passive elastic properties stemming from fibrosis or increased muscle mass but also from derangements in the dynamics of ventricular relaxation., Results: In patients with essential hypertension, all four of the above mechanisms may be operative. Considering the prevalence of hypertension in the general population, hypertension appears to be an important underlying factor in many patients with heart failure on the basis of diastolic mechanisms. In the patient presenting with dyspnea and elevated filling pressures, but with a nondilated, normally contracting ventricle, treatment with standard heart failure medications (such as digitalis, diuretics, and vasodilators) is often ineffective and may be deleterious. Such patients may respond more favorably to beta-blockers and calcium-channel blockers., Conclusions: Diastolic dysfunction should be considered in the patient presenting with heart failure symptoms but with normal systolic function, particularly in hypertensive patients with left ventricular hypertrophy.

Background: In patients with heart failure, activation of the renin-angiotensin system is common and has been postulated to provide a stimulus for further left ventricular (LV) structural and functional derangement. We tested the hypothesis that chronic administration of the angiotensin converting enzyme (ACE) inhibitor enalapril prevents or reverses LV dilatation and systolic dysfunction among patients with depressed ejection fraction (EF) and symptomatic heart failure., Methods and Results: We examined subsets of patients enrolled in the Treatment Trial of Studies of Left Ventricular Dysfunction (SOLVD). Fifty-six patients with mild to moderate heart failure underwent serial radionuclide ventriculograms, and 16 underwent serial left heart catheterizations, before and after randomization to enalapril (2.5-20 mg/day) or placebo. At 1 year, there were significant treatment differences in LV end-diastolic volume (EDV; p less than 0.01), end-systolic volume (ESV; p less than 0.005), and EF (p less than 0.05). These effects resulted from increases in EDV (mean +/- SD, 136 +/- 27 to 151 +/- 38 ml/m2) and ESV (103 +/- 24 to 116 +/- 24 ml/m2) in the placebo group and decreases in EDV (140 +/- 44 to 127 +/- 37 ml/m2) and ESV (106 +/- 42 to 93 +/- 37 ml/m2) in the enalapril group. Mean LVEF increased in enalapril patients from 0.25 +/- 0.07 to 0.29 +/- 0.08 (p less than 0.01). There was a significant treatment difference in LV end-diastolic pressure at 1 year (p less than 0.05), with changes paralleling those of EDV. The time constant of LV relaxation changed only in the placebo group (p less than 0.01 versus enalapril), increasing from 59.2 +/- 8.0 to 67.8 +/- 7.2 msec. Serial radionuclide studies over a period of 33 months showed increases in LV volumes only in the placebo group. Two weeks after withdrawal of enalapril, EDV and ESV increased to baseline levels but not to the higher levels observed with placebo., Conclusions: In patients with heart failure and reduced LVEF, chronic ACE inhibition with enalapril prevents progressive LV dilatation and systolic dysfunction (increased ESV). These effects probably result from a combination of altered remodeling and sustained reduction in preload and afterload.

The hemodynamic determinants of clinical status in patients with left ventricular (LV) systolic dysfunction have not been established. In the present study, preload reserve--LV distension during exercise--was related to clinical status, and the effect of acute angiotensin-converting enzyme inhibition was examined in 97 patients with ejection fraction less than or equal to 0.35 enrolled in the trial, Studies of Left Ventricular Dysfunction (SOLVD). Sixty-one asymptomatic patients (group I) were compared with 36 patients with symptomatic heart failure (group II). Radionuclide LV volumes were measured at rest and during maximal cycle exercise. Group II patients had higher resting heart rates, end-diastolic and end-systolic volumes, and lower ejection fractions (all p less than 0.005). During exercise, only patients in group I had increased stroke volume (from 35 +/- 8 to 39 +/- 11 ml/m2 [mean +/- SD; p less than 0.0005]) due to an increase in end-diastolic volume (from 119 +/- 29 to 126 +/- 29 ml/m2 [p less than 0.0005]), contributing to a greater increase in LV minute output (p less than 0.0001, group I vs group II). After administration of intravenous enalapril (1.25 mg), LV end-diastolic volume response to exercise was augmented in group II (rest, 140 +/- 42; exercise, 148 +/- 43 ml/m2; p less than 0.0005) and LV output response increased slightly (p less than 0.05). Thus, in patients with asymptomatic systolic dysfunction, recruitment of preload during exercise is responsible for maintaining a stroke volume contribution to the cardiac output response.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: To assess the impact of surgical relief of left ventricular outflow obstruction on myocardial perfusion abnormalities in patients with obstructive hypertrophic cardiomyopathy, 20 symptomatic patients who underwent a septal myectomy or mitral valve replacement were studied with assessment of myocardial perfusion during exercise by 201Tl emission computed tomography before and 6 months after surgery., Methods and Results: Before surgery, 15 patients had myocardial perfusion defects during exercise that completely normalized at rest, one patient had both reversible and fixed perfusion defects, two patients had fixed defects only, and two patients had normal exercise and rest thallium scans. After surgical relief of left ventricular outflow obstruction (basal gradient reduced from 62 +/- 40 to 7 +/- 12 mm Hg, p less than 0.001; peak provokable gradient reduced from 131 +/- 27 to 49 +/- 36 mm Hg, p less than 0.001), repeat exercise thallium studies showed complete normalization of perfusion defects in 11 patients, including the two patients with fixed defects alone before surgery, and improvement in the magnitude and distribution of perfusion defects in five additional patients. This was associated with a significant reduction in the number of patients with reversible regional defects (five patients compared with 13 patients before surgery, p = 0.026) and of patients with endocardial hypoperfusion (four patients compared with 12 patients before surgery, p = 0.024). Furthermore, increased lung uptake of thallium was noted in five patients after surgery, compared with 12 patients before surgery (p = 0.055). Only two patients with reversible perfusion defects before surgery had unchanged postoperative studies. However, four patients acquired new fixed defects as a consequence of surgery, and two of these four had the greatest severity and distribution of left ventricular hypertrophy by echocardiography. These four patients experienced a substantially greater decrease in ejection fraction (-26 +/- 15%) after surgery than the remaining patients (-3 +/- 14%, p less than 0.01)., Conclusions: Surgical relief of left ventricular outflow obstruction results in normalization or improvement of myocardial perfusion in the majority of patients with reversible and fixed perfusion defects by 201Tl scintigraphy. However, surgery may result in myocardial injury and scarring, with consequent decreased left ventricular ejection fraction in some patients.

Background: Cardiac tamponade after cardiac surgical procedures is often associated with hemodynamically significant localized pericardial effusions. The localized collection of pericardial effusion in the postoperative period and the atypical presentation of cardiac tamponade limit the use of conventional clinical and echocardiographic signs usually seen with a circumferential pericardial effusion. Observation of left ventricular diastolic collapse in the echocardiogram of a patient with postoperative regional cardiac tamponade prompted us to explore the frequency of this sign in regional cardiac tamponade., Methods and Results: We retrospectively analyzed the echocardiograms of 18 patients with postoperative cardiac tamponade for the following echocardiographic findings: right atrial collapse, right ventricular diastolic collapse, left atrial collapse, and left ventricular diastolic collapse. Three of the 18 patients had circumferential pericardial effusion, and 15 had loculated pericardial effusion; in 10, the effusion was predominantly posterior, and in the other five, it extended laterally or inferiorly. The conventional echocardiographic signs of cardiac tamponade such as right atrial collapse, right ventricular diastolic collapse, and left atrial collapse were present in only 3, 1, and 3 of these 15 patients, respectively, but all exhibited left ventricular diastolic collapse. Increasing pressure within the compartment of a loculated pericardial effusion reaching the limit of pericardial distensibility and consequent transient reversal of transmural left ventricular pressure during diastole are most likely the basis for diastolic collapse of the thick-walled ventricle in a setting of regional cardiac tamponade., Conclusions: We conclude that left ventricular diastolic collapse is a frequent sign of regional cardiac tamponade and could be a useful marker of tamponade in postoperative patients.

Background: Exercise-induced abnormalities during thallium-201 scintigraphy that normalize at rest frequently occur in patients with hypertrophic cardiomyopathy. However, it is not known whether these abnormalities are indicative of myocardial ischemia., Methods and Results: Fifty patients with hypertrophic cardiomyopathy underwent exercise 201Tl scintigraphy and, during the same week, measurement of myocardial lactate metabolism and hemodynamics during pacing stress. Thirty-seven patients (74%) had one or more 201Tl abnormalities that completely normalized after 3 hours of rest; 26 had regional myocardial 201Tl defects, and 26 had apparent left ventricular cavity dilatation with exercise, with 15 having coexistence of these abnormal findings. Of the 37 patients with reversible 201Tl abnormalities, 27 (73%) had metabolic evidence of myocardial ischemia during rapid atrial pacing (myocardial lactate extraction of 0 mmol/l or less) compared with four of 13 patients (31%) with normal 201Tl scans (p less than 0.01). Eleven patients had apparent cavity dilatation as their only 201Tl abnormality; their mean postpacing left ventricular end-diastolic pressure was significantly higher than that of the 13 patients with normal 201Tl studies (33 +/- 5 versus 21 +/- 10 mm Hg, p less than 0.001). There was no correlation between the angiographic presence of systolic septal or epicardial coronary arterial compression and the presence or distribution of 201Tl abnormalities. Patients with ischemic ST segment responses to exercise had an 80% prevalence rate of reversible 201Tl abnormalities and a 70% prevalence rate of pacing-induced ischemia. However, 69% of patients with nonischemic ST segment responses had reversible 201Tl abnormalities, and 55% had pacing-induced ischemia., Conclusions: Reversible 201Tl abnormalities during exercise stress are markers of myocardial ischemia in hypertrophic cardiomyopathy and most likely identify relatively underperfused myocardium. In contrast, ST segment changes with exercise and systolic compression of coronary arteries on angiography are unreliable markers of inducible myocardial ischemia in hypertrophic cardiomyopathy. Apparent cavity dilatation during 201Tl scintigraphy may indicate ischemia-related changes in left ventricular filling, with elevation in diastolic pressures and endocardial compression.

The influence of elastic recoil and restoring forces on diastolic left ventricular pressure decay and minimum left ventricular pressures has been demonstrated in animal models but has not been studied in the human heart. To investigate this issue in the normal human left ventricle, we studied eight patients with chest pain and normal coronary arteries with simultaneous measurement of left ventricular volume (by radionuclide angiography) and pressure (by micromanometer catheter) and coronary sinus blood flow. Electrocardiographic-gated data were obtained in the basal state, during rapid atrial pacing, and during isoproterenol infusion to a similar heart rate. Compared with pacing, isoproterenol increased ejection fraction and reduced end-systolic volume (p less than 0.005), end-systolic pressure (p less than 0.005), and the half-time of pressure decline after peak negative dP/dt (T1/2) (p less than 0.001). Negative diastolic pressure developed in seven of eight patients during isoproterenol (range, -0.5 to -2.4 mm Hg) but in only one of eight during pacing (-0.2 mm Hg). These reduced diastolic pressures during isoproterenol were accompanied by increased stroke volume (reflecting increased transmitral flow) and diminished pulmonary wedge pressure (reflecting left atrial pressure). The magnitude of reduction in minimum diastolic pressure during pacing and isoproterenol was related to the change in end-systolic volume (r = 0.79, p less than 0.001), ejection fraction (r = -0.74, p less than 0.001), T1/2 (r = -0.57, p less than 0.02), and coronary sinus flow (r = 0.73, p less than 0.005). Stronger correlations were observed in analyzing changes during isoproterenol alone.(ABSTRACT TRUNCATED AT 250 WORDS)

To examine the manner in which changes in diastolic performance can contribute to the effect of vasodilation in patients with left ventricular (LV) systolic dysfunction, we examined the effect of acute inhibition of angiotensin converting enzyme with intravenous enalaprilat on early LV diastolic filling. We studied 43 patients with congestive heart failure and depressed LV systolic function (mean ejection fraction +/- SD, 0.24 +/- 0.06), performing radionuclide ventriculography before and after administration of 1.25 mg intravenous enalaprilat. We measured the effect of enalaprilat on the maximum rate of early LV diastolic filling normalized in four different ways and related these changes to both LV and right ventricular (RV) volumes. Enalaprilat induced a small but statistically significant reduction in LV end-systolic volume and increase in LV ejection fraction. For the entire patient group, there was no significant change in LV peak filling rate after enalaprilat administration. For individual patients, however, the effect of enalaprilat on peak filling rate was related to resting RV end-diastolic and end-systolic volumes. In patients with enlarged RV end-diastolic volumes (greater than or equal to 120 ml/m2), mean peak filling rate increased from 1.38 +/- 0.6 to 1.71 +/- 0.6 end-diastolic volumes (EDV)/sec and from 244 +/- 131 to 297 +/- 162 ml/sec/m2 after enalaprilat administration, whereas no change in mean peak filling rate was observed in patients with nondilated RVs. These observations were present regardless of the method of normalizing peak filling rate. Thus, the response of LV peak filling rate to enalaprilat is influenced by the presence of RV dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of verapamil were compared with those of nitroprusside at matched mean arterial pressures and heart rates in 10 symptomatic hypertensive patients during cardiac catheterization. Simultaneous radionuclide angiography and micromanometer pressure measurements were obtained to assess left ventricular pressure-volume relations. Compared with control conditions, verapamil increased left ventricular end-diastolic volume index from 57 +/- 16 to 70 +/- 28 ml/m2 (p = 0.05) without a significant increase in left ventricular end-diastolic pressure (from 10 +/- 4 to 13 +/- 6 mm Hg). Despite a downward and rightward shift in the end-systolic pressure-volume relation indicating negative inotropic effects, ejection fraction did not decrease significantly (from 52 +/- 9% to 46 +/- 9%); cardiac index and stroke volume index remained unchanged. The change in stroke volume index with verapamil was directly related to the magnitude of change in end-diastolic volume index (r = 0.82, p less than 0.005), suggesting that the increase in end-diastolic volume did not arise purely from negative inotropic effects. Systemic vascular resistance index decreased from 42 +/- 8 to 34 +/- 7 mm Hg.min.m2/liter (p less than 0.05). In contrast, nitroprusside decreased left ventricular end-diastolic volume index from 57 +/- 16 to 41 +/- 10 ml/m2 (p less than 0.05), cardiac index from 3.2 +/- 0.7 to 2.8 +/- 0.6 liters/min per m2 (p less than 0.05) and stroke volume index from 28 +/- 6 to 24 +/- 5 ml/m2 (p less than 0.01), with no change in systemic vascular resistance index (40 +/- 10 mm Hg.min.m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Recent studies indicate that reversible 201Tl perfusion defects, compatible with silent myocardial ischemia, commonly develop during exercise in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy (HCM). To determine whether this represents a dynamic process that may be modified favorably by medical therapy, we studied 29 asymptomatic or minimally symptomatic patients with HCM, aged 12-55 years (mean, 28), with exercise 201Tl emission computed tomography under control conditions and again after 1 week of oral verapamil (mean dosage, 453 mg/day). Treadmill time increased slightly during verapamil (21.0 +/- 3.6 to 21.9 +/- 2.7 minutes, p less than 0.005), but peak heart rate-blood pressure product was unchanged (26.3 +/- 6.0 X 10(3) compared with 25.0 +/- 6.4 X 10(3). Two midventricular short-axis images per study were divided into five regions each, and each of these 10 regions was then analyzed on a 0-2 scale by three observers blinded with regard to the patients' therapy. Average regional scores of 1.5 or less were considered to represent perfusion defects, and a change in regional score of 0.5 or more was considered to constitute a significant change. During control studies, 15 patients (52%) developed perfusion defects with exercise (average, 3.7 regions per patient). In 14 of these patients, all perfusion defects completely reversed after 3 hours of rest; one patient had fixed defects. After administration of verapamil, exercise perfusion scores improved in 10 of the 14 patients (71%) with reversible defects; there was overall improvement in 34 of 50 (68%) regions with initially reversible perfusion defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired left ventricular relaxation and filling is an important pathophysiologic mechanism in hypertrophic cardiomyopathy. To determine whether isoproterenol, known to improve relaxation in isolated cardiac muscle, could favorably modify this effect, we assessed simultaneous left ventricular volume and regional systolic asynchrony (by radionuclide angiography), left ventricular pressure (by micromanometer catheters), and lactate metabolism in 12 patients with hypertrophic cardiomyopathy. Pressure-volume relations were studied during atrial pacing stress to induce myocardial ischemia and during isoproterenol infusion to similar heart rates. Angina occurred in 10 patients with pacing and in 11 patients during isoproterenol infusion; lactate consumption was reduced in nine patients during isoproterenol compared with pacing, including five patients who produced lactate with isoproterenol. During isoproterenol compared with pacing, peak left ventricular pressure was higher (205 +/- 33 vs. 142 +/- 21 mm Hg, p less than 0.001), ejection fraction was higher (77 +/- 10% vs. 71 +/- 12%, p less than 0.02), and regional systolic nonuniformity was diminished. Despite ischemia, these changes in load and nonuniformity during isoproterenol were associated with enhanced diastolic function compared with pacing tachycardia: isoproterenol reduced T 1/2, the half-time of pressure decline after peak negative dP/dt (from 46 +/- 10 to 33 +/- 6 msec, p less than 0.001), shifted the diastolic pressure-volume curve downward and rightward in 10 of 12 patients, and increased end-diastolic volume (from 77 +/- 18% to 100 +/- 11% of control values, p less than 0.001) with no change in end-diastolic pressure (19 +/- 7 to 19 +/- 5 mm Hg, p = NS). Thus, despite ischemia, isoproterenol improved left ventricular relaxation and filling compared with tachycardia in the absence of beta-adrenergic stimulation. Although isoproterenol is detrimental in hypertrophic cardiomyopathy by provoking ischemia, these data suggest that the adverse effects of ischemia on ventricular relaxation and distensibility may be alleviated by beta-adrenergic stimulation, possibly as a result of enhanced inactivation and restored load sensitivity.