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Background: Aortic regurgitation (AR) is a valvular disease that can lead to systolic heart failure. Treatment options besides cardiac surgery are limited and consequently severe AR is associated with higher mortality and morbidity when not operated. In this investigation, we examined the effects of a novel cardiac myosin activator, Omecamtiv-mecarbil (OM), in rats with chronic severe AR., Methods: AR was created by retrograde puncture of the aortic valve leaflets in 20 adults Wistar rats. 12 animals survived the acute AR phase and were randomized 2 months thereafter into OM (n = 7) or placebo groups (n = 5). Two rats underwent a sham operation and served as controls. Equal volumes of OM or placebo (NaCl 0.9%) were perfused in the femoral vein by continuous infusion (1.2 mg/kg/hour) during 30 min. Doppler-echocardiography was performed before and at the end of the infusion periods., Results: OM increased indices of global cardiac function (cardiac output, stroke volume), and increased systolic performance (fractional shortening, ejection fraction, left ventricular end systolic diameter) (all p < 0.05). These effects concurred with decreases in indices of LV preload (left atrial size, left ventricular end diastolic diameter) as well in the aortic pre-ejection period / left ventricular ejection time ratio (all p < 0.05). The severity score of the regurgitant AR jet did not change. Placebo infusion did not affect these parameters., Conclusion: The cardiac myosin activator OM exerts favorable hemodynamic effects in rats with experimental chronic AR.

Aortic regurgitation (AR) increases the hemodynamic load on both the left ventricle (LV) and the aorta. Vasodilators and beta-blockers both reduce systemic blood pressure, but their relative effects on the LV and aortic function and aortic regurgitant fraction in chronic AR are uncertain. We aimed to compare short-term effects of losartan and metoprolol on LV and aortic function in asymptomatic patients with chronic moderate to severe AR, both at rest and during exercise, using cardiac magnetic resonance (CMR) imaging. 17 chronic AR patients were randomized to 4-6 weeks losartan followed by metoprolol, or vice versa, in a cross-over design. Aortic regurgitant fraction, aortic distensibility, pulse wave velocity and LV function were assessed at rest and after moderate exercise stress (29 ± 7 W, heart rate increase 25 ± 6 bpm) using CMR. Chronic AR patients on metoprolol had a significantly lower mean heart rate, cardiac power index and rate-pressure product, than on losartan (all p < 0.01). However, aortic regurgitant fraction was greater on metoprolol compared to losartan (by 7 ± 11%, p = 0.02). Metoprolol was also associated with a greater reduction in aortic distensibility during exercise than losartan (- 2.4 ± 1.5 × 10 -3  vs - 1.7 ± 2.1 × 10 -3  mmHg -1 respectively, p = 0.04). End-diastolic volume index was higher on metoprolol than losartan at exercise (difference 6.6 ± 7.8 ml/m 2 , p < 0.01), as was end-systolic volume index (difference 4.0 ± 5.2 ml/m 2 , p < 0.01). Losartan and metoprolol have significantly different short-term effects on aortic regurgitation and LV and aortic function in chronic AR. Further research is required to determine the long-term clinical significance of these changes.

The haemodynamic effects of nicorandil, a new balanced vasodilator exhibiting nitrate-like as well as potassium-channel opening activity in patients with chronic severe valvular lesions have not been reported. We studied the acute effect of nicorandil on haemodynamics in 12 stable patients (6 males, 6 females; mean age 23.5 +/- 4.6 years) with chronic severe valvular regurgitation (8 mitral, 4 aortic). All patients were studied in resting, supine and fasting states. All cardioactive drugs were withdrawn five days prior to the study. Intra-arterial line was placed and thermodilution catheter was positioned in the pulmonary artery. Haemodynamic parameters recorded at baseline and at 30, 60, 90 and 120 minutes following a single oral dose of 20 mg nicorandil revealed no significant change in the heart rate while systemic pressures showed a small decline (p < 0.05). There was significant reduction in systolic, diastolic and mean pulmonary artery pressures (p < 0.001). The mean cardiac index increased from 3.16 L/min/m2 at baseline to 3.77 L/min/m2 at 60 minutes. Both the pulmonary and systemic vascular resistance indices reduced significantly, the peak fall being 18 percent and 29 percent, respectively. Maximal changes were observed at 60 to 90 minutes following administration of nicorandil. No adverse effect of nicorandil occurred during the study. We conclude that nicorandil has a favourable acute haemodynamic effect in patients with chronic severe valve regurgitation. Its long-term use in valvular lesions should be explored further.

Long-term treatment with ACE-inhibitors improves left ventricular function in patients with aortic regurgitation. But how does this advantage influence capacity? Using echocardiography and spiroergometry, we investigated 13 patients before and after a 3 month treatment with cilazapril (2.5-5 mg/d). Ventricular enddiastolic diameter-index decreased from 3.5 to 3.1 cm/m2 (p = 0.005), left ventricular endsystolic diameter-index from 2.3 to 2.0 cm/m2 (p = 0.005), and wallstress from 174 to 150 dyn/cm2 (p = 0.01). Left ventricular mass was reduced by 14% to 488 g (= 253 g/m2, p < 0.05). The regurgitant jet area decreased from 10.1 to 8.1 cm2 (p < 0.05). Wall thickness, workload, and maximal oxygen intake showed no significant difference during follow-up. These results indicate that left ventricular volumes and muscle mass in patients with aortic regurgitation are positively influenced by long term ACE-inhibition, which preserves exercise capacity.

Long-term treatment with angiotensin-converting enzyme (ACE) inhibitors has beneficial effects in patients with chronic aortic regurgitation by reducing left ventricular volumes and regurgitant fraction. Velocity-encoded cine magnetic resonance imaging can directly measure antegrade (forward stroke volume) and retrograde blood flow (regurgitant volume) in the ascending aorta. Velocity-encoded cine magnetic resonance imaging was used in 9 patients with moderate to severe aortic regurgitation (regurgitant fraction 49% +/- 17%) to measure regurgitant fraction, regurgitant volume, and forward stroke volume at baseline and 3 months after therapy with enalapril (mean dose 29 +/- 13 mg). Ten additional patients with aortic regurgitation without any drug therapy served as a control group. In the treatment group, systolic blood pressure slightly decreased from 132 +/- 20 mm Hg to 121 +/- 14 mm Hg (p = not significant), whereas diastolic blood pressure and heart rate (beats per minute) remained unchanged. Regurgitant fraction decreased in 6 patients (responders) from 49% +/- 19% to 39% +/- 20% (percentage change 24% +/- 14%, p = 0.002) and was unchanged in 3 patients (nonresponder, 49% +/- 19% vs 51% +/- 16%; p = not significant). In the responder group, forward stroke volume increased from 128 +/- 32 ml to 148 +/- 57 ml, whereas regurgitant volume remained unchanged (67 +/- 40 ml vs 65 +/- 51 ml). At baseline, the responder group had a significant higher total vascular resistance than the nonresponder group (998 +/- 538 dyne.sec.cm-5 vs 625 +/- 214 dyne.sec.cm-5; p < 0.05). With enalapril treatment, total vascular resistance in the responder group tended to decrease (891 +/- 576 dyne.sec.cm-5), but slightly increased in the nonresponder group (679 +/- 276 dyne.sec.cm-5). The control group showed no changes in regurgitant fraction, regurgitant volume, forward stroke volume, and total vascular resistance at follow-up.

The efficacy of enalapril maleate in dogs with naturally acquired class III or class IV heart failure was evaluated in a multicenter study. Fifty-eight dogs with dilated cardiomyopathy (35 dogs), mitral regurgitation (22 dogs), or aortic regurgitation (1 dog) receiving conventional therapy for heart failure (furosemide with or without digoxin) were included in a randomized double-blind study. Thirty-one dogs received enalapril tablets PO at approximately 0.5 mg/kg body weight bid, and 27 dogs received placebo tablets PO bid. Physical, electrocardiographic, hemodynamic, echocardiographic, radiographic, and clinical examinations were performed on each dog before treatment and at the end of the approximately 21-day study. After treatment on day 0, the enalapril-treated dogs had significantly (P < .05) lower heart rate, mean systemic arterial blood pressure, and mean pulmonary arterial blood pressure than the placebo-treated dogs. Pulmonary capillary wedge pressure was marginally decreased (P = .0567) in the enalapril-treated dogs. When compared with those in the placebo-treated dogs, scores for pulmonary edema were significantly (P < .05) decreased on day 2 in the enalapril-treated dogs. At the end of the study, enalapril-treated dogs had significantly (P < .05) greater decreases in class of heart failure, pulmonary edema score, and mobility score relative to baseline, and had significantly (P < .05) better overall evaluation scores when compared with the placebo-treated dogs. This study shows the beneficial hemodynamic and clinical effects of adding enalapril to conventional therapy for dogs with heart failure.

Objective: Angiotensin converting enzyme (ACE) inhibitors decrease preload and afterload and are therefore of potential value in valvular regurgitation. The present study was designed to assess the effects of treatment for 1 year with an ACE inhibitor on myocardial performance., Patients and Methods: Twenty-four patients with isolated moderate to severe chronic aortic regurgitation or mitral regurgitation who were free of coronary disease were studied before treatment (control) with the ACE inhibitor quinapril and were then followed for 1 year during quinapril therapy (10-20 mg/day)., Results: After 1 year of ACE inhibition, the regurgitant fraction fell by 27 and 42%, compared with control values, in the aortic and mitral regurgitation groups, respectively (P = 0.0001). The left ventricular end-diastolic volume was reduced from 150 +/- 33 to 128 +/- 30 ml/m2 in the aortic regurgitation group, and from 146 +/- 26 to 109 +/- 24 ml/m2 in the mitral regurgitation group (P = 0.0001 for each). End-systolic volume decreased from 55 +/- 27 to 44 +/- 28 ml/m2 in the aortic regurgitation group (P = 0.005) and from 63 +/- 43 to 47 +/- 29 ml/m2 in the mitral regurgitation group (P = 0.002). The left ventricular ejection fraction increased slightly at rest and during exercise in patients with aortic regurgitation, but showed no change in the mitral regurgitation patients after 1 year of quinapril treatment. Echocardiographic studies showed that after 1 year of therapy there was a decrease of about 10% in the left ventricular end-diastolic and end-systolic diameter in both patient groups. Moreover, the left ventricular mass was reduced by 35% in the aortic regurgitation group (P = 0.0001), and left ventricular hypertrophy, which was present in all patients, was reversed completely. In the mitral regurgitation group, a mass reduction of 15% was observed after 1 year of quinapril treatment, and the septal wall thickness, which indicated borderline hypertrophy, decreased to normal., Conclusion: These results demonstrate that long-term ACE inhibition in patients with valvular regurgitation reverses left ventricular dilation and reduces left ventricular mass and hypertrophy, thereby improving left ventricular function. Further, they suggest that ACE inhibition may have the potential to delay aortic or mitral valve replacement.

Nineteen asymptomatic patients affected by isolated chronic aortic regurgitation received 20 mg of nifedipine sublingually: the acute hemodynamic effects of nifedipine were evaluated by combined cross-sectional and Doppler echocardiography. To assess variations in the regurgitant flow volume, the flow volume across the mitral and aortic valves was calculated as the product of velocity-time integral multiplied by the orifice valve area. Flow volume across these valves represented the total stroke volume, and forward stroke volume, respectively: the regurgitant volume was obtained by calculating the difference between total and forward stroke volume. Nifedipine induced a redistribution of the two components of the total left ventricular stroke volume: regurgitant stroke volume decreased from 57 +/- 22 ml/beat to 46 +/- 21 ml/beat (P < 0.002), while forward stroke volume increased from 83 +/- 12 to 93 +/- 15 ml/beat (P < 0.0005), as a consequence of the reduction in systemic vascular resistance from 1513 +/- 378 to 1092 +/- 307 dynes.sec.cm-5 (P < 0.0001). The reduction of regurgitant volume was due to either a 24.8% decrease of the aortic-left ventricular mean pressure gradient during diastole (P < 0.008) or a 6% decrease of the diastolic time interval (P < 0.04). The effect of these acute changes on left ventricular loading was to induce a reduction in oxygen consumption which was expressed by a decrease in the double product (from 10176 +/- 1767 to 9444 +/- 1559 mmHg.beats/min; P < 0.002), in spite of a significant increase in heart rate. This study, therefore, shows the beneficial acute hemodynamic effect induced by nifedipine in asymptomatic patients affected by chronic aortic regurgitation and shows that Doppler-echocardiography is a useful instrument for the evaluation of hemodynamic changes immediately after the administration of drugs.

Seven patients with mitral insufficiency and seven patients with aortic insufficiency were studied by right and left heart catheterization. Hemodynamic observations were made during a control period and during the infusion of phentolamine. Significant declines in the pulmonary artery mean pressure, left ventricular end diastolic pressure, peripheral resistance, and arteriovenous oxygen difference were seen in both groups. The cardiac index increased significantly in the two groups. Phentolamine therapy produced favorable hemodynamic effects because of its vasodilating action as well as its positive inotropic effects.

The hemodynamic effects of isometric exercise and the response to hydralazine therapy were evaluated in 11 patients with chronic, severe aortic regurgitation (AR). Isometric exercise produced a significant increase in heart rate (from 78 +/- 11 to 93 +/- 19 beats/min [mean +/- standard deviation], p less than 0.05), mean blood pressure (from 83 +/- 8 to 104 +/- 20 mm Hg, p less than 0.05), mean right atrial pressure (from 3 +/- 2 to 7 +/- 5 mm Hg, p less than 0.05) and mean pulmonary artery wedge pressure (from 12 +/- 7 to 18 +/- 10 mm Hg, p less than 0.05). Small and insignificant changes were seen in cardiac index (from 3.4 +/- 0.8 to 3.9 +/- 1.0 liters/min/m2), systemic vascular resistance (from 1,097 +/- 257 to 1,171 +/- 284 dynes s cm-5), pulmonary vascular resistance (from 120 +/- 76 to 130 +/- 89 dynes s cm-5) and stroke volume index (from 44 +/- 10 to 43 +/- 12 ml/m2). After oral hydralazine administration (100 to 300 mg), hemodynamic values during isometric exercise were: Heart rate increased further, to 105 +/- 14 beats/min (p less than 0.05), mean blood pressure was 102 +/- 16 mm Hg (difference not significant [NS]) cardiac index increased markedly, to 5.2 +/- 1.4 liters/min/m2 (p less than 0.05), stroke volume index increased to 49 +/- 12 ml/m2 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic regurgitation (AR) was induced in rabbits by aortic valve puncture. Two years later, echocardiography [two-dimensional (2-D) and M-mode; Doppler] was used to monitor acute left ventricular (LV) effects of milrinone. At that time, two of eight AR survivors had hindlimb edema and/or ascites. Baseline LV diameter and wall thickness of AR rabbits was 125-145% for that of sham-operated subjects; mean stroke volume and total LV output (TLVO) were approximately 2.5 x normal; regurgitant fraction was 0.57; and effective (forward) cardiac output (CO) was normal. Basal LV fractional shortening (FS) and mean circumferential fiber shortening velocity (Vcf) were not significantly depressed. Milrinone (10 micrograms/kg/min. i.v.) decreased mean LV stroke volume and TLVO by 25-33% (p less than 0.05). However, forward CO was maintained as regurgitant stroke volume fell an average of 52%. Milrinone significantly reduced aortic mean reverse/mean forward blood flow velocity ratio (-16%) and LV end-diastolic (ED) chamber diameter (-7%), consistent with reduced regurgitation. Mean Vcf was 39% greater than that seen after saline infusion (p less than 0.05). Thus, milrinone promoted Vcf and maintained forward CO in rabbits with chronic compensated AR while appreciably reducing LV regurgitation, chamber size, and total output. These beneficial effects may reflect vasodilating and positive inotropic activities confirmed in normal rabbits.

To determine whether afterload reduction with nifedipine is effective both at rest and during stress tests (rapid atrial pacing and contrast material overload), 14 patients with chronic severe isolated aortic insufficiency (10 asymptomatic) underwent right and left cardiac catheterization. Forty-five minutes after 20 mg of nifedipine (sublingually), left ventricular end-diastolic pressure, peak aortic pressure, systemic vascular resistance and double product decreased significantly at rest, at peak paced rate, and after angiography (P values from less than 0.05 to less than 0.001). Cardiac index increased at resting heart rate (P less than 0.01) but was unchanged during pacing. The reduction of systemic vascular resistances was inversely correlated with its initial value (r = -0.69). After nifedipine, average regurgitant fraction did not change; however its variations were significantly correlated with those of systemic vascular resistance (r = 0.69). It is concluded that in severe aortic insufficiency, nifedipine induces an effective reduction of left ventricular pre- and afterload, accompanied by an enhanced mechanical efficiency (unchanged or increased cardiac index with lower double product), both at rest and during stress tests.

The acute effects of nifedipine (20 mg sublingually) on hemodynamics and cardiac function were studied at rest and during supine bicycle exercise in 20 patients with aortic regurgitation. At rest, heart rate increased by 13%, systemic vascular resistance decreased by 34% and regurgitant index decreased by 17%. The change in systemic vascular resistance was related to its initial rest level (r = 0.82, p less than 0.001) and to the changes in forward cardiac output (r = 0.58, p less than 0.01) and regurgitant index (r = 0.60, p less than 0.01). Left ventricular end-diastolic and end-systolic volumes, stroke volume and ejection fraction were unchanged, whereas right ventricular ejection fraction increased. During exercise, nifedipine administration further increased heart rate by 8% and decreased systemic vascular resistance by 19%. Both forward stroke volume and forward cardiac output increased, but total left ventricular stroke volume was unchanged, resulting in a significant decrease in regurgitant index. Although left ventricular end-diastolic volume was slightly decreased, end-systolic volume did not increase; thus, ejection fraction was higher than that during control exercise (p less than 0.01). Right ventricular ejection fraction increased further. In aortic regurgitation, the acute administration of nifedipine improved cardiac performance and reduced regurgitation at rest and during exercise as a result of afterload reduction and increased heart rate. Whether these beneficial effects will occur during long-term therapy requires further investigation.

We studied the effects of afterload reduction in chronic severe aortic insufficiency by measuring the hemodynamic response to oral hydralazine in 10 consecutive patients. Hemodynamics were also measured during maximal exercise in eight of these patients. At rest, hydralazine reduced pulmonary artery wedge pressure from 14 to 9 mm Hg (p less than 0.01), and increased cardiac index by 70% and stroke volume index by 35% (both p less than 0.001). Before hydralazine, pulmonary artery wedge pressure exceeded 20 mm Hg in five patients during maximal exercise; with hydralazine, at identical levels of exercise, pulmonary artery wedge pressure remained below 20 mm Hg in all patients. For the group, hydralazine reduced pulmonary artery wedge pressure from 21 to 12 mm Hg (p less than 0.05) and increased cardiac index by 31% (p less than 0.05) during exercise; changes in stroke volume index were more variable and there was no significant increase for the group, although several patients increased stroke volume substantially and the overall increase was 34%. These data show that afterload reduction has beneficial effects on cardiac performance in chronic severe aortic insufficiency both at rest and during exercise. Hydralazine may be of use in such patients either in preparation for valve replacement or as interim therapy.

In summary, there investigations indicate that oral hydralazine produces beneficial hemodynamic effects in patients with chronic CHF. These favorable hemodynamic response are observed in the presence or absence of mechanical defects, such as mitral or aortic regurgitation. The predominant hemodynamic effects of hydralazine are substantial increase in CO and SV with decreased systemic vascular resistance. These investigations further suggest that hydralazine therapy not only improves resting cardiac performance, but also cardiac performance during exercise. There is also evidence that improved cardiac performance is sustained at least in some patients during maintenance hydralazine therapy. The impact of hydralazine therapy on the long term prognosis of patients with refractory CHF, however, remains unknown. Nevertheless, the preliminary retrospective studies suggest that in certain subsets of patients with severe chronic CHF, such therapy may provide a better prognosis compared to that expected with conventional therapy.

To assess the hemodynamic effects of afterload reduction in severe aortic regurgitation, nitroprusside was infused at cardiac catheterization in 12 patients with aortic regurgitation. Cardiac hemodynamics, angiographic variables and regurgitant volumes were quantified during control periods, and nitroprusside was infused to reduce systemic systolic pressure to 110 to 125 mm Hg. The following were reduced by the drug: systolic arterial pressure (from 154 +/- 6.4 to 115 +/- 2.3 mm Hg, P less than 0.001); left ventricular end-diastolic pressure (from 23 +/- 2.2 to 11 +/- 1.0 mm Hg, P less than 0.001); systemic vascular resistance (from 1,782 +/- 133 to 1,148 +/- 94 dynes sec cm-5, P less than 0.001); left ventricular end-diastolic volume (from 242 +/- 25 to 196 +/- 19 ml, P less than 0.001); aortic regurgitant fraction (from 0.53 +/- 0.05 to 0.44 +/- 0.06, P less than 0.01); and aortic regurgitant minute volume (from 5.5 +/- 0.10 to 4.3 +/- 0.09 liters/min, P less than 0.01). Effective cardiac index increased (from 2.49 +/- 0.19 to 3.10 +/- 0.24 liters/min per m2, P less than 0.01), and left ventricular ejection fraction rose (from 0.55 +/- 0.03 to 0.61 +/- 0.03, P less than 0.005). These data indicate that afterload reduction with nitroprusside in severe aortic regurgitation improves cardiac performance, greatly decreases left ventricular preload and reduces aortic regurgitant volume. Thus, nitroprusside therapy has special value in severe aortic regurgitation that is of particular benefit in critical clinical conditions.

The hemodynamic response to afterload reduction by sodium nitroprusside was assessed in 5 patients with mitral regurgitation and in 7 with aortic regurgitation. The drug significantly lowered left ventricular systolic pressure, end-diastolic pressure and end-diastolic volume. In patients with mitral regurgitation, significant decreases in regurgitant volume (74 +/- 10 to 44 +/- 7 ml) and regurgitant fraction (60 +/- 4 to 41 +/- 5%) were associated with substantial increases in cardiac output (4.18 +/- 1.18 to 5.43 +/- 1.18 L/min) and forward stroke volume (49 +/- 10 to 64 +/- 9 ml). In patients with aortic regurgitation, vasodilator therapy was effective in increasing forward output only in 2 patients who had an initially elevated end-diastolic pressure which was reduced only to levels slightly above normal with nitroprusside. In patients with a lower level of end-diastolic pressure, further reduction in the filling pressure resulted in no benefit or rather a fall in forward stroke volume, despite a significant increase in pump function (ejection fraction being augmented from 55 +/- 4 to 61 +/- 5%). Experiments in dogs confirmed that nitroprusside reduced the amount of mitral regurgitation by virtue of diminishing the regurgitant orifice size, as a result of the reduction in size of the left heart chamber. These observations also support the concept that it is ultimately important to maintain filling pressure at an optimal level during administration of a vasodilating agent, otherwise effects due to afterload reduction tend to be offset.

Afterload reduction is an accepted therapeutic modality for the treatment of congestive heart failure caused by chronic aortic regurgitation. However, the role of vasodilator therapy in acute aortic incompetence has not been established. To investigate this, left ventricular volume overload was produced in 18 dogs by constructing a valved conduit from the descending thoracic aorta to the left ventricular apex. The time course of aortic, pulmonary and conduit flows was analyzed in eight control studies and established stability of the experimental model. In the remaining 10 dogs, intravenous nitroglycerin, titrated to reduce mean aortic blood pressure by 40%, and placebo (ethanol) were each infused for 20 min periods. Compared with placebo, nitroglycerin significantly reduced aortic flow (3,945 +/- 324 to 3,397 +/- 362 ml/min, p less than 0.01), regurgitant flow (1,304 +/- 131 to 764 +/- 90 ml/min, p less than 0.001), septal-lateral end-diastolic diameter (47.5 +/- 1.8 to 46.5 +/- 1.8 mm, p less than 0.001), left ventricular end-diastolic pressure (6.9 +/- 0.8 to 6.0 +/- 0.6 mm Hg, p less than 0.05), left ventricular stroke work (19.0 +/- 2.6 to 10.8 +/- 1.7 g-m/beat, p less than 0.001) and systemic vascular resistance (2,253 +/- 173 to 1,433 +/- 117 dyne-s/cm5, p less than 0.001). In contrast, pulmonary flow, left anterior descending coronary flow and subendocardial pH did not change during infusion of either nitroglycerin or placebo. These data indicate that by decreasing preload and afterload, and by preserving coronary flow and tissue pH, nitroglycerin effectively reduced ventricular and regurgitant volumes in the setting of acute volume overload.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitroprusside was used to reduce afterload in 13 patients with isolated, severe aortic regurgitation. The drug significantly lowered mean aortic pressure, pulse pressure, left ventricular end-diastolic pressure and left ventricular volume. Total ventricular, or angiographic, cardiac index was generally unaffected, but forward cardiac index was improved significantly in 8 of 13 patients. Augmentation of forward cardiac index was seen in patients with subnormal resting forward cardiac index, in patients with decidedly elevated end-diastolic pressure, and in those with depressed resting ejection fractions. Regurgitant fraction fell with nitroprusside in six patients and remained unchanged in seven. Total stroke work index was diminished in all patients. These data show that afterload reduction in patients with severe aortic regurgitation may improve hemodynamics by reducing aortic regurgitation or by improving ventricular pump function. The lowered total stroke work, reduced ventricular size and improved forward cardiac index imply that afterload reduction may benefit left ventricular failure and delay progressive ventricular dysfunction in patients with aortic regurgitation.