Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group.

BACKGROUND: Despite therapy with diuretics, ACE inhibitors and digoxin morbidity and mortality in heart failure remain high and might respond favorably to an additional vasodilator. METHODS AND RESULTS: Male patients (n=450) with chronic heart failure (cardiac dysfunction and impaired exercise performance) on optimal current therapy (97% enalapril, 89% diuretics) were randomly assigned to double-blind treatment with felodipine extended release (5 mg BID) or placebo for 3 to 39 months (average, 18 months). Felodipine significantly reduced blood pressure and, at 3 months, increased ejection fraction (2.1% versus -0.1% units in the placebo group, P=.001) and reduced plasma atrial natriuretic peptide levels (-2.9 versus 26.9 pg/mL in the placebo group, P=.01) but did not improve exercise tolerance, quality of life, or the need for hospitalization. During long-term follow-up, the favorable effects on ejection fraction and atrial peptide did not persist, but felodipine prevented worsening exercise tolerance and quality of life. In the felodipine and placebo groups, mortality (13.8% versus 12.8%, respectively) and hospitalization (43% versus 42%) rates were similar, and a higher incidence of peripheral edema was the only apparent side effect of felodipine therapy. CONCLUSIONS: Felodipine exerts a well-tolerated additional sustained vasodilator effect in patients with heart failure treated with enalapril, but the only possible long-term benefit was a trend for better exercise tolerance and less depression of quality of life in the second year of treatment. The drug appears to be safe but not clearly efficacious in patients with heart failure.

Thromboembolism and antithrombotic therapy in congestive heart failure.

The incidence of thromboembolic events in unselected patients with class II-III congestive heart failure is 1.6-3.5% per year. Marked limitation of exercise capacity and the presence of echocardiographic left ventricular thrombus appear to be associated with an increased risk of thromboembolism. Several studies have reported that anticoagulant therapy does not eliminate the occurrence of thromboembolism. Because the benefit and risks of anticoagulant therapy in patients with congestive heart failure have not been examined in controlled studies, it is difficult to make well-founded recommendations.

The influence of atrial fibrillation on prognosis in mild to moderate heart failure. The V-HeFT Studies. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Atrial fibrillation occurs commonly in heart failure; however, its importance in terms of prognosis is controversial. METHODS AND RESULTS: We assessed the relation of atrial fibrillation on first Holter monitor to morbidity and mortality in mild to moderate heart failure in 632 patients in the Veterans Affairs Vasodilator-Heart Failure Trial (V-HeFT) I and 795 patients in V-HeFT II: Ninety-nine patients in atrial fibrillation and 533 patients in sinus rhythm were followed for a mean of 2.5 years (range, 6 months to 5.7 years) in V-HeFT I; 107 patients in atrial fibrillation and 688 patients in sinus rhythm in V-HeFT II were followed for a mean of 2.5 years (range, 6 months to 5.0 years). V-HeFT I compared treatment with prazosin, hydralazine-isosorbide dinitrate, and placebo, whereas V-HeFT II compared hydralazine-isosorbide dinitrate with enalapril. Follow-up evaluations included serial Holter monitors, serial metabolic exercise testing, hospitalization data, and clinical examinations. In V-HeFT I, cumulative mortality at 2 years was 0.34 for patients with atrial fibrillation and 0.30 for patients in sinus rhythm (p = 0.25). Overall cumulative mortality was 0.54 for atrial fibrillation patients and 0.64 for sinus rhythm patients (p = 0.86). In V-HeFT II, cumulative mortality at 2 years was 0.20 for patients with atrial fibrillation and 0.21 for patients with sinus rhythm (p = 0.68), and overall cumulative mortality was 0.46 for atrial fibrillation patients and 0.52 for those in sinus rhythm (p < 0.46). Sudden death was not increased with atrial fibrillation in V-HeFT I patients (p = 0.64) or in V-HeFT II (p = 0.68). By multivariate analysis, the relative mortality risk for atrial fibrillation was 0.95 in V-HeFT I and 0.76 in V-HeFT II: Metabolic exercise testing, showed no significant difference in mean change in peak oxygen consumption between patients with atrial fibrillation and those with sinus rhythm in V-HeFT I and a slight decrease late in V-HeFT II: Hospitalization rate for heart failure was not increased in either study. The embolic event rate was not increased for atrial fibrillation patients: 3% versus 4.9% of patients in sinus rhythm (p = 0.41) in V-HeFT I and 4.0% versus 6.0% in V-HeFT II patients (p = 0.44). A secondary analysis compared mortality of patients in atrial fibrillation with that of patients in sinus rhythm on all Holters: Mortality was not increased overall (p = 0.72 in V-HeFT I and p = 0.35 in V-HeFT II). CONCLUSIONS: Atrial fibrillation does not increase major morbidity or mortality in mild to moderate heart failure.

Evaluation by patients with heart failure of the effects of enalapril compared with hydralazine plus isosorbide dinitrate on quality of life. V-HeFT II. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Two new questionnaires concerning the quality of life of patients with heart failure were used in a randomized, controlled trial to determine if the patients' perceptions of the effects of enalapril on their daily activities and sense of well-being were different from those of a group treated with hydralazine and isosorbide dinitrate. METHODS AND RESULTS: The questionnaires were completed at baseline and at 3 months, 6 months, and subsequently every 6 months during follow-up, which averaged 2.5 years (range, 0.5-5.7 years). Data from the questionnaires were reliable as indicated by correlation coefficients between repeated baseline scores of 0.88 and 0.87. Both treatment groups showed a progressive deterioration in quality of life as measured by both questionnaires. The questionnaire scores of the two treatment groups were not significantly different at any follow-up visit. Furthermore, there were no differences between treatments among subgroups defined by baseline questionnaire scores, peak oxygen consumption, ejection fraction, previous vasodilator use, and plasma norepinephrine concentration. CONCLUSIONS: Although several factors may limit the generalization of these results, the lack of a difference with regard to patients' quality of life is an important consideration for the evaluation of the relative therapeutic efficacy of these vasodilators.

Incidence of thromboembolic events in congestive heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: The incidence of thromboembolism and the benefit of anticoagulation in congestive heart failure are controversial. METHODS AND RESULTS: The data base provided by the Veterans Affairs Vasodilator-Heart Failure Trials (V-HeFT I and II) was examined retrospectively to address these issues. In V-HeFT I, 642 men with heart failure were followed an average of 2.28 years, providing 1,464 patient-years of follow-up. In V-HeFT II, 804 men were followed an average of 2.56 years, with 2,061 patient-years of follow-up. Mean left ventricular ejection fraction was 30% in V-HeFT I and 29% in V-HeFT II: Functional capacity was at the interface of classes II and III with a peak exercise oxygen consumption of 14.7 mL.kg-1 x min-1 in V-HeFT I and 13.7 mL.kg-1 x min-1 in V-HeFT II: Warfarin and antiplatelet agents were administered at the discretion of individual investigators. The incidence of all thromboembolic events during 1,068 patient-years without warfarin in V-HeFT I was 2.7/100 patient-years and during 1,188 patient-years in V-HeFT II was 2.1/100 patient-years and was not reduced in patients treated with warfarin. Patients experiencing events had a lower peak exercise oxygen consumption (p < 0.03 in V-HeFT I and p < 0.001 in V-HeFT II) and a lower mean ejection fraction (p = 0.10 in V-HeFT I and p = 0.07 in V-HeFT II). Atrial fibrillation was not associated with an increased risk of thromboembolic events. CONCLUSIONS: The incidence of thromboembolism and stroke in class II or III congestive heart failure is not high and may not be significantly reduced with warfarin treatment. Routine use of anticoagulants in patients with heart failure may not be justified.

Exertional fatigue due to skeletal muscle dysfunction in patients with heart failure.

BACKGROUND: Exertional fatigue in patients with chronic heart failure is usually attributed to skeletal muscle underperfusion. Recently, skeletal muscle atrophy, abnormal muscle metabolic responses, and reduced muscle enzyme levels have been noted in such patients, raising the possibility that some patients may develop muscle fatigue due to intrinsic muscle abnormalities. The present study was undertaken to determine if a subpopulation of patients with heart failure develops exertional fatigue due to skeletal muscle dysfunction rather than to reduced muscle flow. METHODS AND RESULTS: All exercise hemodynamic studies performed in our laboratory on patients with heart failure were reviewed to identify those who exhibited peak exercise VO2 levels < or = 18 ml.min-1 x kg-1 due to leg fatigue and who underwent insertion of a Swan-Ganz catheter and leg blood flow catheter. Thirty-four patients were identified. Six normal subjects were also studied to define normal leg flow and femoral venous lactate responses to exercise. Patients with peak exercise leg flow levels within the normal mean flow level +/- 2 SEM were considered to have normal skeletal muscle flow during exercise. Nine of the 34 patients with heart failure were found to have normal leg blood flow during exercise. All of these patients terminated exercise due to leg fatigue, and all exhibited abnormal increases in femoral venous lactate concentrations (slope of work load versus femoral venous lactate: normal, 0.33 +/- 0.07 mg/W; heart failure with normal flow, 0.81 +/- 0.08 mg/W; p < 0.002). There was no significant difference between patients with normal leg flows and those with reduced flow in age, ejection fraction, and resting hemodynamic measurements. However, patients with normal flows exhibited more normal cardiac output responses to exercise and tended to have higher peak exercise VO2 (14.1 +/- 0.9 versus 11.5 +/- 0.7 ml.min-1 x kg-1, p < 0.05). CONCLUSIONS: A substantial percentage of patients with chronic heart failure develop exertional fatigue due to skeletal muscle dysfunction rather than to reduced skeletal muscle blood flow. In such patients, therapeutic interventions probably should be directed at improving the skeletal muscle abnormalities rather than at improving skeletal muscle flow.

A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure.

BACKGROUND: To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS: Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS: The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination.

Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure: influence of prerandomization variables on the reduction of mortality by treatment with hydralazine and isosorbide dinitrate.

The Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure was designed to determine whether vasodilator drugs could alter the survival of patients with chronic congestive heart failure treated with digoxin and diuretics. Among the 642 patients entered into the study, 273 were randomly assigned to placebo, 186 were randomly assigned to the combination of hydralazine and isosorbide dinitrate, and 183 patients were randomly assigned to prazosin; all patients were followed for periods ranging from 6 months to 5.7 years. Treatment with hydralazine-nitrate produced a 28% reduction in mortality compared with that in patients receiving placebo (95% confidence interval, 3% to 46%), whereas prazosin exerted no apparent beneficial effect. Data were further examined to determine if any baseline variables had an impact on the response to treatment. Mortality in the placebo group was higher in those with coronary artery disease, with a history of antiarrhythmic drug use, and with values lower than the median for ejection fraction and exercise tolerance. A reduction in mortality with hydralazine-isosorbide dinitrate was observed in all of the above pairs of subgroups as well as in those above and below 60 years of age and those with and without a history of hypertension or excess alcohol ingestion. The benefit of hydralazine and isosorbide dinitrate was particularly prominent in younger patients with a lower ejection fraction and those with a history of hypertension and without an alcoholic history.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of maximal bicycle exercise testing with respiratory gas analysis to assess exercise performance in patients with congestive heart failure secondary to coronary artery disease or to idiopathic dilated cardiomyopathy.

Analysis of respiratory gases during maximal treadmill exercise testing has been used in patients with congestive heart failure (CHF) to detect the lactate threshold, presumed to reflect the onset of skeletal muscle underperfusion, and maximal oxygen consumption (VO2), the point at which VO2 plateaus with increasing work due to exhaustion of peripheral oxygen delivery capacity. To determine if this approach is also useful during maximal bicycle exercise testing, ventilatory, hemodynamic and systemic lactate responses to bicycle exercise were measured in 48 patients with CHF. Ventilatory responses also were assessed in 12 normal subjects. Exercise increased VO2 to 24.8 +/- 3.9 ml/min/kg in normal subjects and 13.9 +/- 3.7 ml/min/kg in patients with CHF (p less than 0.001). In all but 1 patient the VO2 increment over the last 3 minutes of exercise was comparable to that in normal subjects exercising over identical work times, suggesting that maximal VO2 was not achieved. Moreover, in patients who exercised for less than 6 minutes, a ventilatory lactate threshold could not be identified. In the 33 patients who exercised longer, a ventilatory lactate threshold was identified in 31 and correlated well (r = 0.81) with blood lactate threshold, as defined by the VO2 at which lactate increased 5 mg/dl over rest levels. However, the 95% confidence limit for predicting blood lactate threshold from ventilatory data was +/- 200 ml/min, a large range relative to the measured ventilatory threshold (570 +/- 132 ml/min). These data suggest that in patients with CHF, respiratory gas analysis during maximal bicycle exercise cannot be used to measure maximal VO2 and provides only a general index of blood lactate behavior.

Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study.

To evaluate the effects of vasodilator therapy on mortality among patients with chronic congestive heart failure, we randomly assigned 642 men with impaired cardiac function and reduced exercise tolerance who were taking digoxin and a diuretic to receive additional double-blind treatment with placebo, prazosin (20 mg per day), or the combination of hydralazine (300 mg per day) and isosorbide dinitrate (160 mg per day). Follow-up averaged 2.3 years (range, 6 months to 5.7 years). Mortality over the entire follow-up period was lower in the group that received hydralazine and isosorbide dinitrate than in the placebo group. This difference was of borderline statistical significance. For mortality by two years, a major end point specified in the protocol, the risk reduction among patients treated with both hydralazine and isosorbide dinitrate was 34 percent (P less than 0.028). The cumulative mortality rates at two years were 25.6 percent in the hydralazine--isosorbide dinitrate group and 34.3 percent in the placebo group; at three years, the mortality rate was 36.2 percent versus 46.9 percent. The mortality-risk reduction in the group treated with hydralazine and isosorbide dinitrate was 36 percent by three years. The mortality in the prazosin group was similar to that in the placebo group. Left ventricular ejection fraction (measured sequentially) rose significantly at eight weeks and at one year in the group treated with hydralazine and isosorbide dinitrate but not in the placebo or prazosin groups. Our data suggest that the addition of hydralazine and isosorbide dinitrate to the therapeutic regimen of digoxin and diuretics in patients with chronic congestive heart failure can have a favorable effect on left ventricular function and mortality.

Hemodynamic effects of vasodilators and long-term response in heart failure.

Hemodynamic responses to vasodilators are commonly assessed when starting long-term vasodilator treatment in patients with chronic left ventricular failure, although the relation between short- and long-term responses is not established. Thus, short- and long-term hemodynamic responses to placebo and vasodilators (isosorbide dinitrate, minoxidil and enalapril or captopril) were measured and long-term clinical efficacy was assessed by changes in exercise capacity after 1 to 5 months of vasodilator administration (plus digitalis and diuretic agents) in 46 patients with New York Heart Association functional class II to IV heart failure caused by cardiomyopathy. There were no significant changes in hemodynamics or exercise capacity during placebo treatment. After initial doses and during long-term administration of vasodilator drugs, hemodynamics were significantly improved. After long-term vasodilator treatment, maximal oxygen uptake during exercise increased by 2.9 +/- 5.7 ml/min per kg from a control value of 14.1 +/- 5.6 ml/min per kg (p less than 0.01), and exercise duration also increased by 1.8 +/- 3.5 minutes (p less than 0.01). Changes in maximal oxygen uptake, however, did not correlate with short-term changes in pulmonary wedge pressure (correlation coefficient [r] = -0.14), cardiac index (r = -0.01) or systemic vascular resistance (r = -0.20). Long-term hemodynamic changes also failed to correlate with changes in exercise capacity. Baseline hemodynamics, cardiac dimensions and left ventricular ejection fraction before vasodilator administration all failed to correlate with baseline exercise capacity or with long-term changes in exercise capacity. Thus, hemodynamic measurements at initiation or during follow-up of vasodilator therapy do not relate to long-term clinical efficacy assessed by exercise capacity in patients with chronic left ventricular failure. Therefore, the rationale for making invasive hemodynamic measurements before initiating long-term vasodilator therapy for heart failure is questioned.

Enalapril (MK-421), a new angiotensin-converting enzyme inhibitor. Acute and chronic effects in heart failure.

Enalapril (MK-421) is a new oral angiotensin-converting enzyme inhibitor which was administered to eight patients with chronic congestive heart failure. Four hours after enalapril administration (10 to 20 mg), mean arterial pressure fell from 95.6 +/- 11.4 (SD) to 84.8 +/- 17.6 mm Hg (p less than 0.05), systemic vascular resistance fell from 18.5 +/- 3.0 to 15.8 +/- 4.1 units (p less than 0.02), while pulmonary artery wedge pressure changed insignificantly from 17.5 +/- 9.2 to 14.5 +/- 10.2 mm Hg and cardiac index rose insignificantly from 2.63 +/- 0.46 to 2.82 +/- 0.75 L/min/m2. These hemodynamic effects persisted during one month of enalapril administration. Baseline plasma renin activity of 0.76 +/- 1.07 ng/ml/hr rose to 3.23 +/- 2.87 ng/ml/hr (p less than 0.05) after one month of enalapril administration. During the month of enalapril administration, maximal exercise duration rose from 465.1 +/- 233.0 to 572.3 +/- 233.7 seconds (p less than 0.05), and maximal oxygen uptake increased from 12.3 +/- 2.7 to 16 +/- 11.2 ml/min/kg (p less than 0.05). No major side effect occurred. These sustained effects may be clinically beneficial, and enalapril deserves further evaluation in the long-term treatment of patients with chronic congestive heart failure.

Arrhythmia prophylaxis using propranolol after coronary artery surgery.

Sixty patients undergoing coronary artery bypass grafting operations with cold potassium cardioplegia as the method of myocardial preservation either received low-dose oral propranolol (10 mg every 6 hours; 28 patients) or served as controls (32 patients). The study period began after extubation and ended at the time of hospital discharge. On the fourth postoperative day, 24-hour Holter monitoring was performed to assess additional subtle differences in arrhythmias. The overall incidence of symptomatic postoperative arrhythmias was 31% in the control group: 6 patients (19%) had atrial fibrillation or flutter and 4 patients (12%), ventricular arrhythmias. By contrast, 1 patient (4%) in the propranolol group had atrial fibrillation, and no patient had ventricular arrhythmias. The difference in overall arrhythmia rates between the two groups is significant (p less than 0.025). Twenty-four-hour Holter monitoring demonstrated no additional differences in the frequency of simple or complex atrial or ventricular ectopy between the two groups. We conclude that the incidence of postoperative arrhythmias following coronary artery bypass operation is diminished by the oral administration of prophylactic low-dose propranolol. When compared with our previous study [1], in which the method of myocardial preservation was intermittent aortic cross-clamping and moderate hypothermia, there is no difference in the overall incidence of postoperative arrhythmias.

Effect of diuresis on the performance of the failing left ventricle in man.

To determine the effect of diuresis on the performance of the failing left ventricle, we measured cardiac output, pulmonary wedge pressure and M-mode echo left ventricular diastolic dimension before and after diuresis in 13 patients with heart failure. Diuresis increased stroke volume (43 +/- 23 ml to 50 +/- 18 ml (p less than 0.05)) and decreased pulmonary wedge pressure (28 +/- 3 mm Hg to 19 +/- 5 mm Hg (p less than 0.01)), mean blood pressure (100 +/- 14 mm Hg to 88 +/- 10 mm Hg (p less than 0.01)) and systemic vascular resistance (2,059 +/- 622 dynes-sec-cm-5 to 1,783 +/- 556 dynes-sec-cm-5 (p less than 0.05)). Echo left ventricular diastolic dimension was not changed by diuresis (6.0 +/- 0.8 cm to 6.0 +/- 0.8 cm). Percent change in stroke volume correlated with systemic vascular resistance (r = 0.60, p less than 0.05) and with left ventricular diastolic dimension (r = 0.62, p less than 0.05) but not with pulmonary wedge pressure (r = 0.12) or right atrial pressure (r = 0.04). Thus, diuresis improved the performance of the failing ventricle and reduced afterload, but it did not alter left ventricular diastolic dimension, an index of preload. These data suggest that diuresis improves ventricular function by decreasing afterload.

Ethmozin: a new antiarrhythmic agent developed in the USSR. Efficacy and tolerance.

Ethmozin, a phenothiazine derivative, was developed in the Soviet Union as a new antiarrhythmic agent. We evaluated ethmozin using a controlled single-blinded in-hospital protocol in 14 ambulatory patients with ventricular ectopy ranging from an average of 48 to 1,801 depolarizations per hour and in eight patients with atrial ectopy ranging from 63 to 693 depolarizations per hour. Placebo was administered for the first 3 days, followed by ethmozin from 2.4 to 11.2 mg./Kg./day administered orally every 8 hours for 7 days and concluding with placebo for the final 3 days. Continuous 24-hour long-term electrocardiographic monitoring for 13 days was employed to measure drug efficacy accurately. Six of eight (75 per cent) patients with atrial ectopy and 10 of 14 (71 per cent) patients with ventricular ectopy had statistically significant reductions in ectopy during ethmozin therapy. Atrial ectopy was reduced at a lower dose and plasma level of ethmozin than was ventricular ectopy. With the exception of mild nausea in one patient, no side effects of ethmozin therapy were noted. Ethmozin appears to be a well-tolerated, effective antiarrhythmic agent with a dosage regimen that can promote patient compliance for long-term use.

Limitations of routine long-term electrocardiographic monitoring to assess ventricular ectopic frequency.

Variations in the frequency of ventricular premature depolarizations (VPDs) were evaluated with three consecutive 24-hour long-term electrocardiography monitor recordings from 15 clinically stable patients with various cardiac disorders. Mean hourly VPD frequencies ranged from 37--1,801 per hour. Data were subjected to 4 and 5 factor nested analyses of variance. The extent of spontaneous variation in arrhythmia frequency that occurred in individual patients from day to day was 23%, between 8-hour periods within days was 29%, and from hour to hour was 48%. In addition, the variability between repeated three-day monitoring periods over time was quantified in five patients and found to be 37%. This analysis determined that to distinguish a reduction in VPD frequency attributable to therapeutic intervention rather than biologic or spontaneous variation alone required a greater than 83% reduction in VPD frequency if only two-24-hour monitoring periods were compared, and greater than 65% reduction if two 72-hour periods were compared. The limitations of routine 24-hour electrocardiographic monitoring must be considered in diagnostic and therapeutic decision-making.

Acute severe aortic regurgitation. Pathophysiology, clinical recognition, and management.

Acute severe aortic regurgitation is a relatively unfamiliar, though life-threatening, disease. We review its diverse causes, anatomic faults, and hemodynamic sequelae and set the stage for an understanding of the clinical manifestations in light of their physiologic mechanisms. Clinical information includes the natural history, physical signs (physical appearance, systemic arterial pulse, jugular venous pulse, precordial palpation, auscultation), electrocardiogram, and chest roentgenogram. Echocardiographic features are especially emphasized and the need for prompt diagnosis and surgical intervention underscored, even in the setting of active infective endocarditis.