SUMMARYIn order to evaluate the circulatory action of vasodilator therapy in patients with significant mitral regurgitation, sodium nitroprusside was infused intravenously in 14 patients who had mitral regurgitation due to a variety of causes. In 13 of these patients, valvular insufficiency had been present for several years. The mean arterial pressure fall from 88 ± 1.2 to 71 ± 2.1 mm Hg was accompanied by a significant decrease in pulmonary artery pressure (from 27.4 ± 2.7 to 19.1 ± 2.4 mm Hg), pulmonary artery wedge v wave (from 31.7 ± 3.3 to 17.0 ± 1.9 mm Hg), and left ventricular end-diastolic pressure (from 16.7 ± 1.6 to 9.3 1.2 mm Hg). In 10 patients significant decreases in angiographic end-diastolic volumes (from 196 10 to 177 ± 10 ml) and end-systolic volumes (from 90 ± 10 to 77 ± 9 ml) were accompanied by slight decreases in the total stroke volume and slight increases in the ejection fraction. The improved forward stroke volume index (from 27 3.0 to 33 ± 2.1 ml) was due to a very significant reduction in the regurgitant fraction (from 57 ± 6 to 42 6%). Nitroprusside, therefore, has beneficial hemodynamic effects in patients with chronic mitral regurgitation. Circulation, Volume 50, November 1974 valvular disease.3 In order to quantitate the changes which occur and to relate them to the severity of disease in a larger group of patients with chronic mitral regurgita.tion of moderate degree, we studied 14 patients at the time of diagnostic cardiac catheterization during control periods and during infusion of nitroprusside in doses large enough to profoundly influence the circulatory state of the patient. Methods Patients StudiedFourteen patients with significant mitral insufficiency were studied at the time of diagnostic cardiac catheterization. The nature of the study and all risks were explained to each patient and informed consent was obtained. There were eight females and six males, ranging in age from 31 to 68 years, with a mean of 54 years. The etiology of the mitral regurgitation was rheumatic in eight, idiopathic ruptured chordae tendineae in two, papillary muscle dysfunction related to coronary artery disease in two, prolapse of the posterior leaflet of the mitral valve in one, and bacterial endocarditis with perforation of the anterior leaflet of the mitral valve in one. In all patients, except one with bacterial endocarditis, the valvular insufficiency was chronic, being of greater than three years' duration. Clinically, all patients were class III, New York Heart Association functional classification, and had clinical evidence of cardiomegaly. All were taking digitalis and diuretics at the time of the study. The clinical diagnosis of mitral insufficiency was confirmed in all patients by a left ventriculogram performed by the retrograde arterial approach. In 10 patients, a second left ventriculogram was performed during nitroprusside infusion for evaluation of changes in ventricular volumes. Nine

The effect of digoxin on atrioventricular (a-v) conduction was compared in five patients with an intact cardiac autonomic nervous system (Group I) and seven patients who had undergone cardiac transplantation (Group II), in whom we have previously shown the transplanted heart to be completely denervated. Small decreases in the atrial effective refractory period (ERP) (from 262 plus or minus 12 to 254 plus or minus 11 msec) and atrial functional refractory period (FRP) (from 304 plus or minus 12 msec) were observed in Group I patients after digoxin, but these changes were not significant. However, significant increases in the A-V nodal ERP (from 315 plus or minus 18 msec to 351 plus or minus 17 msec, P less than 0.05), and A-V nodal FRP (from 426 plus or minus 42 to 460 plus or minus 46 msec, P less than 0.01) were produced by digoxin and were unrelated to changes in cycle length. In Group II patients with denervated hearts, changes in atrial ERP (from 246 plus or minus 4 to 243 plus or minus 6 during spontaneous sinus rhythm; from 204 plus or minus 10 to 216 plus or minus 8 msec during atrial pacing) and atrial FRP (from 311 plus or minus 12 to 316 plus or minus 11 msec during spontaneous sinus rhythm; from 254 plus or minus 12 to 260 plus or minus 10 msec during atrial pacing) were not significant. However, in contrast to the Group I patients, the digoxin-induced changes in A-V nodal ERP (from 280 plus or minus 22 to 297 plus or minus 18 msec during atrial pacing) and FRP (from 368 plus or minus 18 to 377 plus or minus 18 msec during spontaneous sinus rhythm; from 334 plus or minus 13 to 346 plus or minus 16 msec during atrial pacing) were also statistically insignificant. Our results demonstrate that the electrophysiologic effects of digoxin on atrioventricular conduction in man are most marked in the atrioventricular node and are dependent on cardiac innervation

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Echocardiography has proven to be a useful technique in the diagnosis and assessment of therapy in idiopathic hypertrophic subaortic stenosis (IHSS). Asymmetric septal hypertrophy has been described as the pathognomonic anatomic marker of the disease. A characteristic systolic anterior motion of the anterior mitral valve leaflet has been detected in the presence of hemodynamically significant subaortic left ventricular outflow obstruction. An echocardiographic quantification of the outflow gradient (the obstruction index) has been derived previously. Four patients were studied by ultrasound at the time of cardiac catheterization. All four demonstrated systolic anterior motion of the anterior mitral leaflet in the absence of a resting gradient. In three of the four, the calculated obstruction index predicted hemodynamically significant resting gradients. All four patients were shown to have labile gradients with provocative maneuvers. A fifth patient with abnormal systolic anterior motion demonstrated a close correlation between the obstruction index and resting gradient; however, symmetric hypertrophy of the septum and left ventricular posterior wall was detected by ultrasound. Therefore, the abnormal mitral valve pattern may be seen in the absence of a resting gradient and symmetric left ventricular hypertrophy may exist in the presence of IHSS.

Vasodilator therapy has been shown to have beneficial effects in heartfailure. In order to evaluate the haemodynamic actions of vasodilator administration in primary congestive cardiomyopathy, sodium nitroprusside was infused intravenously at a rate of 15 to 100 ,g/min to 12 patients. Mean arterial pressure fell 15 per cent from 86±3-0 to 72±2-4 mmHg (11-40±.4 to 9-6+0'3 kPa), and there was a small but significant decrease in mean heart rate from 96±4.8 to 90±4 4 beats/min. These changes were accompanied by a significant decrease in mean pulmonary artery pressurefrom 40 ±2-2 to 26 ±2-8 mmHg (5 3±0 3 kPa to 3 5±+04 kPa), mean pulmonary capillary wedge pressure from 25±22 to 16±21 mmHg (3-3±0O3 to 21±03 kPa), and left ventricular end-diastolic pressure from 27+1-8 to 17±1-5 mmHg (36±03 to 2-3±02kPa). Cardiac index increased by an average of 48 per centfrom 2-1 to 31 l/min per m2, and left ventricular stroke work index increasedfrom 18-4±16 to 21-3±1-9g M/M2. These results show that pronounced left ventricular dysfunction in patients with congestive cardiomyopathy is improved during vasodilator therapy.The clinical course in congestive cardiomyopathy is and impedance to left ventricular ejection, further frequently marked by repeated episodes of cardiac depressing myocardial function. Recently, vasodilafailure. Progressive left ventricular dilatation is ac-tor therapy has been shown to improve left vencompanied by increased left ventricular wall stress, tricular function in patients with congestive heart decreased myocardial efficiency, and further de-failure of diverse aetiologies (Franciosa et al., 1972; pression of myocardial performance. The prognosis Guiha et Chatterjee et al., 1973a). In of these patients is poor, with almost 50 per cent order to assess the potentially beneficial haemodying within 12 months of the onset of pulmonary dynamic effects of a vasodilator agent in congestive congestion, and two-thirds dying within 2 years cardiomyopathy, 12 patients were studied before and (Hamby et al., 1970). during nitroprusside infusion. Prolonged periods of bed rest have been advocated with modest results (McDonald, Burch, and Walsh, 1971). Diuretics and inotropic agents have Subjects and methods been the traditional methods of treatment in an attempt to decrease left ventricular filling pressure Twelve patients with congestive cardiomyopathy and increase cardiac output. Such therapy may were investigated at the time of diagnostic cardiac initially produce symptomatic relief; however, catheterization. Informed consent was obtained further deterioration is inevitable, and a downhill after the nature of the study and risks were excourse ensues. Reliance on the digitalis glycosides plained in detail to the patients. The subjects in the setting of cardiomyopathy is associated with a comprised 11 men and one woman, ranging in age high incidence of toxicity. from 21 to 65 years, with a mean age of 43 years.Reflex arteriolar vasoconstriction in heart failure Clinically, all patients had symptoms of New York produc...