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Chronic effects of myocardial infarction on right ventricular function: a noninvasive assessment.

To assess the chronic effects of myocardial infarction on right ventricular function, 48 subjects were studied utilizing radionuclide angiography and two-dimensional echocardiography. Ten were normal subjects (group I), 11 had previous inferior wall myocardial infarction (group II), 10 had previous anteroseptal infarction (group III), 11 had combined anteroseptal and inferior infarction (group IV) and 6 had extensive anterolateral infarction (group V). The mean (+/- standard deviation) left ventricular ejection fraction was 0.66 +/- 0.03 in group I, 0.58 +/- 0.02 in group II, 0.52 +/- 0.02 in group III, 0.33 +/- 0.03 in group IV and 0.33 +/- 0.01 in group V. No systematic correlation between left and right ventricular ejection fraction was observed among the groups. The mean right ventricular ejection fraction was significantly reduced in the presence of inferior myocardial infarction (0.30 +/- 0.03 in group II and 0.29 +/- 0.03 in group IV compared with 0.43 +/- 0.02 in group I [p less than 0.001]). The group II and IV patients also had increased (p less than 0.001) right ventricular end-diastolic area and decreased (p less than 0.001) right ventricular free wall motion by two-dimensional echocardiography. In the presence of anteroseptal infarction (group III), right ventricular free wall motion was increased (p less than 0.05) compared with normal subjects (group I). Thus, the effects of prior myocardial infarction on right ventricular function depend more on the location of infarction than on the extent of left ventricular dysfunction. Inferior infarction was commonly associated with reduced right ventricular ejection fraction and increased right ventricular end-diastolic area. The right ventricular free wall excursion was increased in the presence of anteroseptal infarction, suggested loss of contribution of interventricular septal contraction to right ventricular ejection.

Adult↗

Influence of coronary collaterals on left ventricular function in patients undergoing coronary angioplasty.

The purpose of this study was to determine the role of coronary collaterals on global left ventricular function during transient coronary occlusion. Left ventricular systolic function was evaluated noninvasively in 37 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) by means of peak aortic blood acceleration measured with a continuous-wave Doppler velocity meter placed suprasternally. Doppler measurements were made before, during, and immediately after balloon inflation. Nineteen patients underwent PTCA of the left anterior descending coronary artery, 15 of the right coronary artery, and three of the circumflex coronary artery. All patients had a subtotal coronary occlusion. Among the 37 patients 23 had no angiographic evidence of collaterals supplying the vessel undergoing PTCA and 14 had collaterals. In patients without collaterals peak acceleration was 16.0 +/- 3.0 m/sec/sec before balloon occlusion and decreased to 11.8 /+- 3.6 m/sec/sec within 30 to 40 seconds of coronary occlusion (p less than 0.001). After 30 to 40 seconds of reperfusion (balloon deflated), peak acceleration returned to near- preocclusion levels (17.3 +/- 7.5 m/sec/sec). Among patients with collaterals peak acceleration remained unchanged during balloon occlusion and reperfusion relative to preocclusion levels (NS). These data indicate that collaterals can preserve left ventricular function during transient coronary occlusion in humans.

Angioplasty, Balloon↗

Aortic valve stenosis: fatal natural history despite normal left ventricular function and low invasive peak-to-peak pressure gradients.

For many years, the severity of valvular aortic stenosis (AS) was evaluated mainly on the basis of cardiac catheterization. In many centers, the handy peak-to-peak transvalvular pressure difference or 'peak-to-peak gradient' in relation to left ventricular function was used as a crucial feature in taking a decision regarding valve substitution. In a prospective study during the period 1994-1997, 150 consecutive patients with AS were examined systematically using cardiac catherization as well as transthoracic (TTE) and transesophageal echocardiography. The study was performed in order to compare the diagnostic accuracy and reproducibility of the three modalities with the purpose of improving our evaluation strategy. We found that the three methods were able to determine the aortic valve area with similar accuracy and reproducibility. The data thus support earlier papers and the currently recommended strategy of managing most patients on the basis of TTE since this approach is more rapid and gentle to the patients. In accordance with the past policy of our department, however, considerable weight was put on the invasive data during the study period. Thus, 12 patients with invasive peak-to-peak gradient <50 mm Hg and no severe depression of left ventricular function were not offered valve replacement, despite symptoms and significant valve area reductions. At 2.5 years of follow-up, 6 had died, 3 of severe heart failure, 2 while awaiting scheduled valve replacement, and 1 during aortocoronary bypass surgery. Another 3 patients later experienced further symptom progression and underwent successful aortic valve replacement. In the remaining 3 patients, all free from coronary stenoses and other valvular heart disease than AS, heart failure symptoms had worsened considerably during continued medical therapy. In conclusion, we do not recommend consideration of the peak-to-peak gradient in the process of deciding whether or not AS patients should receive valve replacement. A low peak-to-peak gradient does not exclude severe AS, even in the presence of preserved left ventricular function.

Aged↗

[Physical training in coronary patients with poor left ventricular function].

Physical training is beneficial in patients with coronary artery disease, and in those after myocardial infarction in whom left ventricular function and ejection fraction (LVEF) are relatively well preserved. However, little is known about the effect of physical training in coronary patients with impaired left ventricular function. 12 patients after myocardial infarction (range 42-60 years) with LVEF of 30% or less at rest were evaluated after 11 months of isotonic physical training. Mean LVEF increased from 28.0% to 33.0% (p less than 0.002) at rest and from 29.4% to 33.2% (p less than 0.002) on effort. Exercise tolerance increased 228 seconds by the end of the study (p less than 0.001); the double product at symptom limit effort increased (p less than 0.001) and the double product at the same work load decreased (p less than 0.002). During training there was no cardiovascular deterioration and all patients returned to work within a mean of 3.7 months. The results show that patients with severe left ventricular impairment should not necessarily be excluded from cardiac rehabilitation programs involving physical training.

Adult↗

Assessment of left ventricular function by noninvasive methods.

The possibility of evaluating left ventricular function by noninvasive methods is discussed in detail. The methods that are considered are electrocardiograph, phonocardiography, apex cardiography, sphygmography, impedance cardiography, electrokymography, and echocardiography. Following a brief section of 'definitions', each method is described in detail including technical problems, difficulties, and results. The systolic time intervals and the stress tests are briefly discussed. Based on modern experimental studies, the stress test should include both an electro- and a phonocardiogram. In the latter, one would measure the amplitude of the first heart sound as an index of contractility. The conclusion is that combined methods give the best results. They are electrocardiography, phonocardiography, impedance cardiography, and echocardiography. An alternative, dictated by technical problems, is to use at first phonocardiography and impedance plus electrocardiography; then echocardiography plus electrocardiography; and then, if indicated, a stress test might complete the study; the latter should include both an electrocardiogram and a phonocardiogram.

Adult↗

Combined effect of the force-frequency and length-tension mechanisms on left ventricular function in patients with dilated cardiomyopathy.

BACKGROUND: The myocardial length-tension and the force-frequency relations are important mechanisms that regulate the contractile strength of the heart. AIMS: To evaluate in humans the effect on left ventricular function of the interaction between the myocardial length-tension and force-frequency relations. METHODS AND RESULTS: Eight patients with dilated cardiomyopathy (DCM) and 6 control subjects underwent radionuclide monitoring of left ventricular function during atrial pacing, saline loading and atrial pacing at the end of saline loading. In controls, atrial pacing reduced left ventricular end-diastolic (P < 0.001) and end-systolic volumes (P < 0.001) with no change in ejection fraction whereas after volume expansion end-diastolic volume (P < 0.001) and ejection fraction (P < 0.001) increased. Atrial pacing after volume expansion increased ejection fraction (P < 0.05). In patients with DCM, ejection fraction was reduced during atrial pacing (P < 0.001) and volume expansion (P < 0.05) due to an increase in left ventricular end-systolic volume (P < 0.001). Pacing tachycardia after volume expansion further increased end-systolic volume and reduced ejection fraction with a significant 'pacing by load' interaction (P < 0.001). Peak filling rate increased at each step in controls while it remained unchanged in patients with DCM. CONCLUSION: The heart rate increase during left ventricular distension improves ventricular function in normals and has detrimental effects in patients with DCM.

Adult↗

Assessment of left ventricular function by the midwall fractional shortening/end-systolic stress relation in human hypertension.

OBJECTIVES: This study examined left ventricular performance in relatively unselected hypertensive patients by use of physiologically appropriate midwall shortening/end-systolic stress relations. BACKGROUND: Supranormal left ventricular function has been reported in hypertensive patients, possibly due to an artifact of mismatching endocardial rather than midwall fractional shortening to mean left ventricular end-systolic stress. METHODS: Samples of 474 hypertensive patients (150 women, 324 men) and 140 normal subjects (68 women, 72 men) were drawn from a large urban employed population. The inverse relations (p < 0.0001) of both echocardiographic endocardial and midwall fractional shortening to end-systolic stress in normal subjects were used to calculate the ratios of observed to predicted endocardial and midwall fractional shortening in hypertensive patients. Midwall shortening was calculated from an elliptic model, taking into account the epicardial migration of the midwall during systole. RESULTS: Use of midwall fractional shortening in hypertensive patients reduced the proportion of patients with function above the 95th percentile of normal from 22% to 4% (p < 0.0001) and fractional shortening as a percent of predicted from 107% (p < 0.001 vs. 100% in normotensive control subjects) to 95% (p < 0.0001; p < 0.001 vs. 101% in normotensive control subjects). Midwall shortening was below the 5th percentile of normal in 16% of hypertensive patients instead of 2% with endocardial shortening (p < 0.0001): They tended to be older than other hypertensive patients and had concentric left ventricular hypertrophy. Among hypertensive patients, those with concentric left ventricular hypertrophy or remodeling had reduced midwall shortening as a percent of predicted from end-systolic stress (p < 0.0001). CONCLUSIONS: Use of the physiologically more appropriate midwall shortening/end-systolic stress relation 1) markedly reduces the proportion of hypertensive subjects identified as having high endocardial left ventricular function; and 2) identifies a substantial subgroup of patients with reduced left ventricular function who have concentric geometry of the left ventricle, a pattern associated with high cardiovascular risk.

Adult↗

A miniature cesium iodide-photodiode detector for ambulatory monitoring of left ventricular function.

The physical characteristics of a portable nonimaging scintillation probe system for continuous ambulatory monitoring of the left ventricular function are described. The detector of the equilibrium radionuclide labeled blood pool is a single cesium iodide (CsI) crystal coupled to a silicium photodiode and interfaced to a microcomputer. The spatial properties of this small CsI crystal (1 x 1 x 1 cm3) were evaluated with various single-hole collimators. Linearity was studied in nonattenuating medium. Saturation began at 3000 cps, count loss was 10% at 4000 cps, maximal count rate was 24,000 cps. In attenuating medium, isocount curve of 5% of the maximal count rate was 100 mm deep and 160 mm wide. The most appropriate tested lead collimator to record the global ejection fraction of the left ventricle was a disc-shaped (thickness 5 mm, diameter 41 mm) single-hole (proximal aperture 8 mm, distal aperture 18 mm) collimator. Sensitivity was similar to the sensitivity of a sodium iodide nuclear probe. The detection performance appeared comparable to other available detector systems. Our results indicate that such a CsI-photodiode probe is a promising candidate for left ventricular function monitoring. The application to an ambulatory multicrystal detector system is presented and discussed.

Biophysical Phenomena↗

Left ventricular function and chronotropic responses after normothermic cardiopulmonary bypass with intermittent antegrade warm blood cardioplegia in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Recent studies indicate that normothermic cardiopulmonary bypass (CPB) with intermittent antegrade warm blood cardioplegia (IAWBC) may have metabolic and clinical advantages, but limited data exist on its effects on myocardial function. Therefore, we investigated the acute effects of this approach on systolic and diastolic left ventricular function and on chronotropic responses. METHODS: In 10 patients undergoing isolated CABG we obtained on-line left ventricular pressure-volume loops using the conductance catheter before and after normothermic CPB with IAWBC. Steady state and load-independent indices of left ventricular function derived from pressure-volume relations were obtained during right atrial pacing (80-100-120 beats/min) to determine baseline systolic and diastolic function and chronotropic responses. RESULTS: The mean time of CPB was 105+/-36 min (median 103, range 60-167 min) with a mean aortic cross-clamp time of 75+/-27 min (median 69, range 43-129 min). Baseline (80 beats/min) end-systolic elastance (E(ES)) did not change after CPB (1.22+/-0.53 to 1.12+/-0.28 mm Hg/ml, P>0.2), while the diastolic chamber stiffness constant (k(ED)) significantly increased (0.014+/-0.005 to 0.040+/-0.007 ml-1, P=0.018) and relaxation time constant (tau) significantly decreased (61+/-3 to 49+/-2 ms, P=0.004). Before CPB, incremental atrial pacing had no significant effects on E(ES) and tau but significant negative effects on kED (0.014+/-0.005 to 0.045+/-0.012 ml-1, P=0.013). After CPB, atrial pacing had significant positive effects on E(ES), tau and kED (E(ES): 1.12+/-0.28 to 2.60+/-1.54 mm Hg/ml, P=0.021; tau: 49+/-2 to 45+/-2 ms, P=0.009; kED: 0.040+/-0.007 to 0.026+/-0.005 mm Hg, P=0.010), indicating improved systolic and diastolic chronotropic responses. CONCLUSION: On-pump normothermic CABG with IAWBC preserved systolic function, increased diastolic stiffness, and improved systolic and diastolic chronotropic responses. Normalization of the chronotropic responses post-CPB is likely due to effects of successful revascularization and subsequent relief of ischemia.

Aged↗

[Cinegeometric analysis of left ventricular function in normals and in patients with isolated stenosis of the ramus anterior descendens (author's transl)].

The left ventricular function was evaluated by a cineangiographic method. 28 normals and 36 patients with an isolated stenosis of the anterior descending branch of the left coronary artery underwent this procedure. From single plane RAO-LV-cineangiograms following parameters were calculated: LV-volumens (EDV, ESV) according to the area-length method, ejection fraction (EF), percentage shortening of the medial perpendicular short axis (delta M, delta MPL), mean velocity of circumferential fiber shortening (VCF, VCFPL). Patients with comparable ramus anterior descendens branch findings can have normal- or abnormal pattern of LV-contraction. The critical cineangiographic parameters of left ventricular function are significantly decreased at rest in ramus anterior descendens lesions with normal systolic anterior wall motion in comparison to the normal collective. Hypokinesis, Akinesis and aneurysms deteriorate parameters of LV-function.

Angiocardiography↗

Detection of silent ischemia adds to the prognostic value of coronary anatomy and left ventricular function in predicting outcome in unstable angina patients.

BACKGROUND: Patients with unstable angina are at increased risk of unfavourable outcomes such as myocardial infarction, death and urgent revascularization. Early risk stratification may improve subsequent outcome. Recently the presence and duration (at least 60 mins) of silent ischemia as measured by Holter monitoring has been shown to be of prognostic value. The incremental value of this information over that provided by coronary angiography and assessment of left ventricular function is not known. OBJECTIVE: To determine whether detection of silent ischemia is of independent and additional prognostic significance beyond that provided by the angiographic extent of coronary artery disease and left ventricular dysfunction. METHODS: One hundred and thirty-five unstable angina patients with 24 h of ST segment monitoring in addition to early cardiac catheterization (4 +/- 3 days) were assessed. Eighty-nine patients (66%) had ST segment shift for a total of 593 episodes (mean duration of 18 +/- 30 mins per episode) of which 92% were asymptomatic. Ten patients had a myocardial infarction and six patients died during the hospitalization. In addition, there were 33 urgent revascularization procedures. RESULTS: With the generalized additive logistic model, various clinical variables were assessed for predicting unfavourable outcomes. Duration of ST shift (P = 0.02) was second only to angiographic severity of coronary artery disease (P = 0.004) as a predictor. In the presence of these two variables left ventricular function did not have independent prognostic significance (P = 0.16). Event-free survival curves show that duration of ST shift of at least 60 mins was of incremental value in predicting unfavourable in-hospital outcomes compared with both the extent of coronary artery disease and left ventricular dysfunction. CONCLUSION: In patients with unstable angina, further stratification can be achieved early with Holter monitoring in addition to coronary angiography and assessment of left ventricular function.

Angina, Unstable↗

Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.

OBJECTIVE: To determine the importance of rhythm regulation or rate control in patients with permanent atrial fibrillation (AF) and normal left ventricular function. PATIENTS AND INTERVENTIONS: Thirty six patients with a mixed fast and slow ventricular response rate to their AF were randomised to either His bundle ablation (HBA) and VVIR pacemaker (HBA group) or VVI pacemaker and atrioventricular modifying drugs (Med group). Outcomes assessed at one, three, six, and 12 months included exercise duration and quality of life. RESULTS: Exercise duration significantly improved from baseline in both groups. There was no difference in outcome between the groups (Med +40% v HBA +20%, p = NS). The heart rate profile on exercise was similarly slowed in both groups compared to baseline. Quality of life significantly improved in both treatment arms for the modified Karolinska questionnaire (KQ) (Med +50% v HBA +50%, p = NS) and the Nottingham health profile (NHP) (Med +40% v HBA +20%, p = NS). However, for the individual symptom scores of each questionnaire more were improved in the Med group (KQ-Med 6 improved v HBA 4, NHP-Med 3 v HBA 1). Left ventricular function was equally preserved by both treatments during follow up. CONCLUSION: In these patients control of ventricular response rate with either HBA + VVIR pacemaker or atrioventricular modifying drugs + VVI pacemaker will lead to a significant improvement in exercise duration and quality of life. Rhythm regulation by HBA did not confer additional benefit, suggesting rate control alone is necessary for the successful symptomatic treatment of these patients in permanent AF.

Aged↗

Ventricular venting during coronary revascularization: assessment of benefit by intraoperative ventricular function curves.

Although the physiological benefits of left ventricular venting during cardiopulmonary bypass have been documented experimentally, air embolus is still a concern clinically, and surgeons, therefore, continue to debate whether or not to vent routinely during coronary revascularization. In this study, 10 patients vented during revascularization and 10 not vented were studied immediately before and after cardiopulmonary bypass using Sarnoff ventricular function curves to assess changes in ventricular performance. Stroke work index by each patient before and after bypass was compared at common left atrial pressures and concomitant similar systemic resistances. In patients who were vented, there was overall no change in function (98 +/- 7% of control; range, 146--73%). In patients who were not vented, there was overall significant depression of function (67 +/- 5% of control; range, 91--45%, p less than 0.01). The overall absence of depression in patients who were vented, several of whom had very poor ventricles before bypass, strongly supports venting for coronary revascularization.

Cardiopulmonary Bypass↗

Left ventricular function and infarct size 20 months after primary angioplasty for acute myocardial infarction.

OBJECTIVE: To study changes in left ventricular function and infarct size during long-term follow-up after acute myocardial infarction treated with primary angioplasty. DESIGN: From 1996 to 1998, 100 consecutive patients were treated with primary angioplasty for acute ST-elevation myocardial infarction. Angioplasty was successful in 95% of the patients. Global left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography before discharge, after 6 weeks and after a mean follow-up time of 20 months. Infarct size was assessed by technetium 99m-tetrofosmin myocardial perfusion tomography (SPECT) at rest, performed at the same time intervals. RESULTS: Mean LVEF was 56% at discharge, 55% after 6 weeks and 57% after 20 months of follow-up. No significant improvement in LVEF was observed. Only 8% of the patients at follow-up had LVEF lower than 40%. After 1 week, a mean perfusion defect of 19% was measured by SPECT. After 6 weeks and 20 months of follow-up, the mean perfusion defects were reduced to 14% (p < 0.001) and 15%, respectively. CONCLUSION: Left ventricular function was well preserved with a mean LVEF of 57% 20 months after primary angioplasty for acute myocardial infarction. No significant change in LVEF was observed from 1 week after angioplasty to follow-up. Infarct sizes as assessed by SPECT imaging with tetrofosmin were reduced from 1 to 6 weeks, but did not change further during long-term follow-up. The reduction in the perfusion defects over time was probably due to gradual relief of stunning.

Angioplasty, Balloon, Coronary↗

Does warm blood retrograde cardioplegia preserve right ventricular function?

BACKGROUND: Efficacy of warm blood retrograde cardioplegia in preserving right heart function remains controversial. The current study was conducted to gauge the preservation of right ventricular function after warm blood retrograde cardioplegia. METHODS: We studied 75 consecutive patients undergoing isolated heart valve procedures with warm blood retrograde cardioplegia as the exclusive mode of preservation. Right ventricular radionuclide ejection fraction and hemodynamic measurements using a pulmonary artery catheter were calculated before and within 3 days after operation. RESULTS: Postoperative radionuclide right ventricular ejection fraction was well preserved at 0.4686 +/- 0.0122 compared with 0.4327 +/- 0.0255 preoperatively (p = 0.7064). Right ventricular systolic work index improved from 5.82 +/- 0.52 to 8.97 +/- 0.60 g x m/m2 (p < 0.0001) and cardiac index increased from 2.40 +/- 0.09 to 2.92 +/- 0.11 L/m2 (p < 0.0001). When right ventricular systolic work index was correlated with preload, 30 patients moved up and down on the same ventricular function curve and 42 moved to a higher inotropic curve postoperatively. Only 3 patients demonstrated decreased inotropy. CONCLUSIONS: In the clinical setting warm blood retrograde cardioplegia used as the exclusive mode of myocardial preservation provides adequate protection of the right heart.

Adult↗

Continuous monitoring of left ventricular function by an ambulatory radionuclide detector in patients with coronary artery disease.

Global left ventricular function and a modified V5 electrocardiographic (ECG) lead were continuously monitored by a radionuclide recorder in 12 normal subjects and 39 patients with coronary artery disease while the subjects were performing various daily activities. The ambulatory studies revealed that walking on a level surface caused 11 of 12 normal subjects and 18 of 32 patients to increase their left ventricular ejection fraction by greater than 6% units. A transient decrease in left ventricular ejection fraction (6 to 18%) lasting greater than or equal to 1 min was observed on 36 occasions in 16 patients with coronary artery disease; 12 episodes were accompanied by chest pain or shortness of breath and 24 were asymptomatic. Electrocardiographic ST segment depression suggestive of ischemia was recorded in 6 of the 12 symptomatic and 5 of the 24 asymptomatic episodes. In 10 of the 12 symptomatic episodes, left ventricular ejection fraction began to decrease 30 to 90 s before the onset of symptoms. These studies suggest that continuous monitoring of both left ventricular function and the ECG may permit stratification of episodes of ST depression suggesting ischemia by the degree of left ventricular dysfunction they produce.

Activities of Daily Living↗

Left ventricular function in cyanotic congenital heart disease.

Left ventricular function was studied with quantitative biplane cineangiocardiography in 39 preoperative and 23 postoperative patients with cyanotic congenital heart disease. Diagnoses included pulmonary atresia or critical pulmonary stenosis with intact ventricular septum (group 1), tricuspid atresia (group 2) and pulmonary atresia with ventricular septal defect (group 3). Preoperative patients ranged in age from 1 day to 7 years and postoperative patients from 7 weeks to 23 years. Left ventricular end-diastolic volume was increased in preoperative patients in groups 1 and 2 (132 and 136 percent of normal, respectively) but was normal in patients in group 3. Left ventricular ejection fraction was decreased to a similar extent in preoperative groups 1 to 3: 0.54, 0.55 and 0.56, respectively. After a shunt procedure left ventricular end-diastolic volume increased to 228 and 266 percent of normal in groups 1 and 2, respectively, but remained within normal limits in group 3. Left ventricular ejection fraction was normal in postoperative group 1 patients, whose ages averaged 1.8 years, but remained decreased in group 2 and 3 patients, whose ages averaged 8.1 and 5.6 years, respectively. Duration of cyanosis and degree of left ventricular dilatation appear to be important variables in regard to pump function in patients with cyanotic congenital heart disease.

Adolescent↗

Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart.

BACKGROUND: The basic pharmacology of the third-generation beta-blocking agent carvedilol differs considerably from second-generation compounds such as metoprolol. Moreover, carvedilol may produce different, ie, more favorable, clinical effects in chronic heart failure. For these reasons, we compared the effects of carvedilol and metoprolol on adrenergic activity, receptor expression, degree of clinical beta-blockade, hemodynamics, and left ventricular function in patients with mild or moderate chronic heart failure. METHODS AND RESULTS: The effects of carvedilol versus metoprolol were compared in two concurrent placebo-controlled trials with carvedilol or metoprolol that had common substudies focused on adrenergic, hemodynamic, and left ventricular functional measurements. All subjects in the substudies had chronic heart failure resulting from idiopathic dilated cardiomyopathy. Carvedilol at 50 to 100 mg/d produced reductions in exercise heart rate that were similar to metoprolol at 125 to 150 mg/d, indicating comparable degrees of beta-blockade. Compared with metoprolol, carvedilol was associated with greater improvement in New York Heart Association functional class. Although there were no significant differences in hemodynamic effects between the carvedilol and metoprolol active-treatment groups, carvedilol tended to produce relatively greater improvements in left ventricular ejection fraction, stroke volume, and stroke work compared with changes in the respective placebo groups. Carvedilol selectively lowered coronary sinus norepinephrine levels, an index of cardiac adrenergic activity, whereas metoprolol did not lower coronary sinus norepinephrine and actually increased central venous norepinephrine levels. Finally, metoprolol was associated with an increase in cardiac beta-receptor density, whereas carvedilol did not change cardiac beta-receptor expression. CONCLUSIONS: The third-generation beta-blocking agent carvedilol has substantially different effects on left ventricular function, hemodynamics, adrenergic activity, and beta-receptor expression than dose the second-generation compound metoprolol. Some or all of these differences may explain the apparent differences in clinical results between the two compounds.

Adrenergic beta-Antagonists↗