Barry M. Massie

Oral hydralazine therapy for chronic refractory heart failure.

SUMMARY The hemodynamic effects of oral hydralazine were investigated in ten patients (nine in NYHA Class IV and one in Class III) with chronic refractory heart failure. With hemodynamic monitoring, adequate oral doses of hydralazine (50 or 75 mg) were determined and then administered every six hours. Hemodynamics were determined at 2–3, 6–8 and 24 hours on hydralazine therapy. Arterial pressure decreased slightly (5%) and systemic vascular resistance decreased significantly (42%). Cardiac and stroke volume index increased by 70 and 66%, respectively, without any significant change in heart rate, pulmonary capillary wedge or right atrial pressure. Hemodynamic improvement was associated with clinical improvement without a major complication. During the follow-up period of 3–7 months, seven of nine patients were in NYHA Class II and one in Class III. One other patient died suddenly six weeks after discharge. These findings suggest that hydralazine is an effective oral vasodilator for the treatment of refractory heart failure.

Deleterious Effects of Hydralazine in Patients with Pulmonary Hypertension

Thirteen consecutive patients with primary and secondary pulmonary hypertension who had normal left ventricular function were treated with hydralazine in an effort to reduce pulmonary vascular resistance and clinical symptoms. Despite marked decreases in systemic vascular resistance (40 per cent; P less than 0.001), hydralazine produced only moderate decreases in pulmonary arteriolar resistance (21 per cent), without improving stroke volume or pulmonary-artery pressure. Instead, mean arterial pressure fell markedly (17.5 mm Hg, P less than 0.01) in association with a reflex increase in heart rate (11 beats per minute, P less than 0.01). Four patients became symptomatically hypotensive within 24 hours of the initiation of treatment; two of these four required pressors for circulatory support, and one died. Progressive renal insufficiency developed in one patient, and a symptomatic decrease in systemic arterial oxygen saturation occurred in another; both changes were reversed upon discontinuation of the drug. In conclusion, hydralazine fails to produce consistent hemodynamic and clinical benefits in patients with primary and secondary pulmonary hypertension, and it frequently causes serious adverse reactions.

The noninvasive identification of left main and three-vessel coronary artery disease by myocardial stress perfusion scintigraphy and treadmill exercise electrocardiography.

The usefulness of exercise electrocardiography (ECG) and myocardial stress perfusion scintigraphy (SPS) in the noninvasive identification of patients with left main or three-vessel coronary artery disease (CAD) was assessed. Ninety-six patients with chest pain were divided into three groups. Group I consisted of 44 patients with left main or three-vessel CAD. Group 2 included 37 other patients with CAD. Group 3 comprised 15 patients with normal coronary arteries. Standard criteria for positive and nondiagnostic SPS and ECG were used. Markedly positive patterns of SPS and ECG suggestive of left main or three-vessel CAD were defined. Forty-two (95%) group 1 patients had positive SPS and 28 (64%) had positive exercise ECG (p < 0.005). Twenty-four (65%) group 2 patients had positive SPS (p < 0.005 compared with group 1) and 14 (38%) had positive ECG (p < 0.05 compared with group 1). No group 3 patient had a positive SPS and three (20%) had positive ECG. Markedly positive SPS and ECG each detected only 19 (43%) and 15 (34%) group 1 patients, respectively. ECG or SPS were markedly positive in 30 (68%) group 1 patients, significantly increasing the diagnostic yield (p < 0.005). The specificity of markedly positive SPS (95%) for left main or three-vessel CAD was higher than markedly positive ECG (86%), but not statistically different. SPS is more sensitive than ECG for the diagnosis of CAD in patients with left main or three-vessel CAD. However, SPS and ECG have low sensitivity for the accurate identification of this subgroup of patients with high-risk anatomy. Two scintigraphic patterns have been characterized that are specific for left main or threevessel CAD. These patterns, in conjunction with ECG, allow noninvasive identification of 68% of symptomatic patients with left main or three-vessel CAD.

Beneficial effects of hydralazine in severe mitral regurgitation.

The severity of mitral regurgitation is, in part, determined by aortic impedance to left ventricular outflow. Sodium nitroprusside acutely decreases regurgitant flow, but the importance of its dual vasodilating effects, the lowering of peripheral vascular resistance and increasing of venous capacitance, is unclear. We studied the hemodynamic response to intravenous hydralazine, which selectively acts on the arteriolar resistance bed, in 10 patients with severe mitral regurgitation. Hydralazine produced a 50% increase in forward stroke volume (22 +/- 2 to 33 +/- 3 ml/m2, P less than 0.001) and a 33% reduction in regurgitant stroke volume (40 +/- 6 to 27 +/- 6 ml/m2, P less than 0.001), with a resultant fall in pulmonary capillary wedge v wave and mean pressures. Unlike nitroprusside, it did not alter left ventricular end-diastolic volume or pressure. Oral hydralazine maintained this hemodynamic improvement for at least 48 hours and, in three patients, provided more sustained clinical improvement. We conclu...

Relationship of regional myocardial perfusion to segmental wall motion: a physiologic basis for understanding the presence and reversibility of asynergy.

SUMMARY Experimental work has shown that even small reductions in myocardial perfusion impair contractile performance. We, therefore, studied the relationship between regional perfusion, assessed by thallium- 201 scintigraphy and segmental wall motion, quantitated on biplane contrast ventriculograms, in patients with coronary artery disease. We evaluated 270 segments in 54 patients, including 27 without evidence of myocardial infarction. Most normally perfused regions (125 of 140) contracted normally, whereas those with scintigraphic defects at rest were usually asynergic (42 of 46). Surprisingly, 57% (48 of 84) of regions with exercise-induced perfusion defects were also asynergic, including 48% (25 of 52) of those in patients without myocardial infarction. In 22 patients who had intervention ventriculograms, improvement of perfusion abnormalities at rest correlated closely with reversibility of asynergy. Although there was an association between the location and severity of coronary artery stenosis and segmental wall motion, myocardial perfusion during exercise was a significantly better predictor of asynergy.These findings suggest that resting asynergy may occur even in patients without previous infarction, predominantly in regions with jeopardized perfusion. Asynergy in regions with exercise-induced perfusion abnormalities may, therefore, be an indicator of resting ischemia and may be reversible by coronary artery revascularization.

Association between the exercise ejection fraction response and systolic wall stress in patients with chronic aortic insufficiency.

We studied the exercise ejection fraction response in 56 patients with chronic aortic insufficiency. All had left ventricular dilatation but preserved resting ejection fraction and minimal or no symptoms. The exercise ejection fraction increased by 0.05 units or greater in 18 (32%) patients (group I), remained within 0.05 units of the resting value in 18 (32%) patients (group II), and fell by 0.05 units or greater in 20 (36%) patients (group III). There were no significant differences among the groups in left ventricular end-diastolic dimension, end-systolic dimension, or fractional shortening by echocardiography or in resting left ventricular volumes and ejection fraction by radionuclide angiography. Left ventricular end-systolic wall stress was significantly higher in group III than in either group I or group II (89 +/- 20 vs 70 +/- 18 and 69 +/- 17 X 10(3) dyne/cm2; p less than .005). At peak exercise there were no differences among groups in systolic blood pressure. However, end-systolic volume increased from 65 +/- 28 to 77 +/- 36 ml/m2 in group III and fell from 50 +/- 21 to 28 +/- 18 ml/m2 in group I during exercise. Thus, at peak exercise end-systolic volume was nearly three times greater in group III than in group I. Although stress could not be determined directly during exercise, the directional changes in its determinants suggest that it also would have been higher in group III patients. A highly significant inverse correlation was present between the ejection fraction response and the change in end-systolic volume (r = -.87, p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial perfusion scintigraphy in patients with mitral valve prolapse: Its advantage over stress electrocardiography in diagnosing associated coronary artery disease and its implications for the etiology of chest pain.

Patients with mitral valve prolapse (MVP) frequently experience chest pain which may, expecially in older subjects and males, be difficult to differentiate from angina pectoris. Electrocardiographic (ECG) changes, ventricular arrhythmias, metabolic abnormalities and rare reports of myocardial infarction and sudden death further suggest the presence of an ischemic process in these patients. The recognition of accompanying coronary artery disease (CAD) and exclusion of other causes of ischemia, therefore, may be important in determining the prognosis and appropriate therapy for such patients. We performed stress ECGs and perfusion scintigrams in 25 patients with confirmed MVP who underwent cardiac catheterization or evaluation of chest pain. Stress ECGs were not helpful in iagnosing associated CAD, primarily because of a high incidence 53%, 10/19) of false positive tests, and had only a 48% overall accuracy. cintigraphy was more accurate (P < 0.001), correctly classifying all patients. Scintigraphy was uniformly negative in patients with normal coronary arteriograms, suggesting that ischemia, if present as the cause of chest pain and ECG changes, must be either very localized or generalized.