Comparison of haemodynamic effects of oral prazosin, oral hydralazine, and intravenous nitroprusside in same patients with chronic heart failure.

British Heart Journal, 1979, 42, 664-670 Comparison of haemodynamic effects of oral prazosin, oral hydralazine, and intravenous nitroprusside in same patients with chronic heart failure' JAWAHAR MEHTA, MARIE IACONA, CARL J. PEPINE, AND C. RICHARD CONTI From the Cardiology Section, Veterans Administration Medical Center and Division of Cardiology, Department of Medicine, College of Medicine, Gainesville, Florida, USA The haemodynamic effects of oral prazosin and hydralazine were evaluated in patients with refractory heart failure and compared with those of intravenous nitroprusside in the same patients. Both oral agents were well tolerated and appeared to have beneficial haemodynamic effects. Prazosin and hydralazine produced similar increases in cardiac output associated with a similar decrease in systemic vascular resistance. Prazosin resulted in a more significant decline in left ventricular filling pressure and pulmonary vascular resistance than did hydralazine. Haemodynamic alterations induced by prazosin were similar to those induced by nitroprusside, which suggests a relatively balanced reduction of preload and afterload. With hydralazine, the increase in cardiac output without change in left ventricular filling pressure or pulmonary vascular resistance suggests miniimal effect on preload but significant reduction in afterload. SUMMARY A decrease in left ventricular afterload in patients with heart failure improves left ventricular function by increasing stroke volume and decreasing left ventricular filling pressure (Franciosa et al., 1972; Chatterjee et al., 1973a; Guiha et al., 1974). This has been shown in heart failure associated with a variety of pathological states, such as coronary heart disease (Franciosa et al., 1972; Chatterjee et al., 1973a), mitral and aortic regurgitation (Chatterjee et al., 1973b; Bolen and Alderman, 1976), and hypertensive heart disease (Majid et al., 1971). Reduction of preload lowers left ventricular filling pressure but does not consistently result in increased stroke volume (Franciosa et al., 1974; Mantle et al., 1976). Intravenously administered nitroprusside produces a rapid increase in cardiac output and fall in left ventricular filling pressure in certain patients with heart failure as a result of afterload and preload reduction. Because nitroprusside must be given parenterally, its usefulness is limited to patients in hospital. Thus, it would be clinically useful if oral agents with a similar mode of action were available to increase stroke volume and decrease pulmonary congestion in patients with heart failure. In ambulant patients with heart failure, both hydralazine (Chatterjee et al., 1976b; Franciosa et al., 1977; Mehta et al., 1978b) and prazosin (Awan et al., 1977; Mehta et al., 1978a) have shown promise in preliminary studies. However, in individual patients with heart failure, the haemodynamic response to vasodilators can vary (Chatterjee and Parmley, 1977). We therefore compared the haemodynamic and clinical effects of various vasodilator agents in the same patients. This study was designed so that the effects of two oral vasodilator agents, hydralazine and prazosin, could be evaluated, and the effects of these compared with those induced by intravenous nitroprusside in the same patients. Patients and methods The subjects were 11 male patients, aged 37 to 65 years, with symptoms and signs of clinical heart failure (New York Heart Association class III or IV) despite treatment with digitalis, diuretics, and salt restriction. The duration of heart failure ranged from 3 to 7 years before study. In all, heart failure 'Presented in part at the Annual Scientific Session of the was the result of coronary heart disease, docuAmerican College of Cardiology, Anaheim, California, March mented by history, electrocardiogram, and previous coronary angiography. None complained of angina 1978. pectoris at the time of study. Each of these patients Received for publication 6 June 1979 664 Comparison of haemodynamic effects of vasodilators 665 had areas of abnormal left ventricular wall motion observed during left ventriculography, and all had an enlarged heart. A left ventricular diastolic gallop was heard in seven patients. Basal riles were present in seven. All patients were in sinus rhythm, though three had occasional atrial or ventricular ectopic beats. These clinical observations were made before haemodynamic study. Index of myocardial oxygen demand = SAP x HR. (Abbreviations: CI, cardiac index: CO, cardiac output; BSA, body surface area; SV, stroke volume; HR, heart rate; LVSWI, left ventricular stroke work index; SVI, stroke volume index; Ao, arterial mean pressure; LVFP, left ventricular filling pressure; SVR, systemic vascular resistance; PVR, pulmonary vascular resistance; PA, pulmonary arterial mean pressure; and SAP, arterial systolic pressure. Patients were evaluated clinically during the control period and hourly during drug administration. HAEMODYNAMIC STUDIES The procedure and drugs to be used were explained to the patients, and their informed consent was given. Investigations were performed in a special study room of the cardiac care unit, so that haemodynamic variables could be monitored and recorded for the duration of study. Digitalis was continued, but diuretic agents (hydrochlorothiazide 50 mg daily in six patients and frusemide 40 mg daily in the other five) and nitrates were withheld for two days before study. These agents were discontinued so that haemodynamic variables were affected primarily by the study drugs rather than the acute effects of diuretics and nitrates. The patients were kept at bed-rest for at least eight hours before and throughout the study period. A triple lumen flowdirected catheter was advanced to the pulmonary artery, and a 'teflon' catheter was introduced percutaneously into the radial artery to measure systemic blood pressure. Systemic and pulmonary arterial pressures and pulmonary artery wedge pressure were recorded on a VR-6 recorder (Electronics for Medicine, White Plains, NY) with Statham P23Ia strain gauge transducers. Systolic and diastolic pressures were averaged from at least 10 beats measured over two respiratory cycles. Mean pressures were obtained by electronic filtration. The occluded pulmonary artery pressure recorded during balloon inflation was taken as pulmonary artery wedge pressure and agreed closely with pulmonary artery diastolic pressure in each patient; either of these measurements was used as an index of left ventricular filling pressure. All pressure measurements were recorded with reference to midchest zero with the patient supine. Heart rate was averaged from recordings of a standard electrocardiographic lead. Cardiac output was measured in triplicate by thermodilution (Ganz and Swan, 1972) and reported as the average of these three determinations. The following calculations were made: CI (1/min per M2)=CO/BSA SV (ml/beat)=CO/HR SVI (ml/beat pe (...truncated)