Nitroprusside in Refractory Heart Failure

Sodium nitroprusside infused in 18 patients with intractable heart failure (nine with ischemic heart disease and nine with cardiomyopathy) produced a prompt reduction of left ventricular filling pressure (pulmonary wedge or left ventricular end diastolic pressure) from an average of 32.2 to 17.2 mm Hg and a rise in cardiac output from an average of 2.98 to 5.2 L/minute. Mean arterial pressure fell by 15 mm Hg and heart rate was slightly but significantly slowed. Stroke volume and forward ejection fraction were nearly doubled. Responses were similar in ischemic heart disease and cardiomyopathy. A diuresis and natriuresis accompanied the infusion and the clinical response was sustained in five patients in whom the drug was continued for 24–72 hours. These results suggest that intractable heart failure may be effectively treated by reduction in impedance to left ventricular ejection.1 In the 1970s, heart failure refractory to diuretics and digitalis was a common medical problem that required frequent hospitalization. Treatment consisted of aggressive diuresis with very modest improvement in symptoms of congestion and electrolyte disturbances. Patients were weak, associated with low cardiac output, and the only alternatives were prolonged bed rest or cardiac transplant. Until the publication of this landmark manuscript,1 the authors comment that “in recent years considerable effort has been expended in the development of potent diuretic and new inotropic drugs that might improve the circulatory state… by increasing myocardial contractility…. However, little attention has been directed to the systemic vascular resistance or the outflow impedance that influences afterload and it is another important determinant of left ventricular performance.”1 The hemodynamic effects of nitroprusside in the treatment of patients with heart failure changed the clinical outlook of this disease. During my residence years in Buenos Aires, I had the opportunity to work with one of the authors, Dr Mikulic, who brought this concept (put forth by Jay Cohn and colleagues) to Argentina. I saw firsthand the clinical improvement of these patients. This concept of peripheral vascular resistance as a therapeutic target in heart failure revolutionized the management of patients. In addition, it paved the way to the development of oral agents that are used today (such as the combination of isosorbide dinitrate and hydralazine). I would like to conclude this historical vignette with the final paragraph of the manuscript. The authors wrote “The potential place of vasodilator drugs in the therapeutic armamentarium for heart failure remains to be established. On the basis the present experience intravenous therapy with nitroprusside… should be an effective means of reducing pulmonary capillary pressure, improving left ventricular performance and enhancing peripheral perfusion…. However, orally effective drugs with a similar site of action need to be developed to evaluate the efficacy of chronic therapy. Preliminary experience suggests that long-acting nitrates like nitroglycerin may fulfill the prerequisites for such a drug….”1