RELATION OF NEUROHUMORAL ACTIVATION TO CLINICAL-VARIABLES AND DEGREE OF VENTRICULAR DYSFUNCTION - A REPORT FROM THE REGISTRY OF STUDIES OF LEFT-VENTRICULAR DYSFUNCTION

Objectives. This study examined the relation between neurohumoral acti vation and severity of left ventricular dysfunction and congestive hea rt failure in a broad group of patients with depressed left ventricula r function who were not recruited on the basis of eligibility for a th erapeutic trial. Background. Previous studies have established the pre sence of neurohumoral activation in patients with severe congestive he art failure. It is not known whether the activation of these neurohumo ral mechanisms is related to an impairment in left ventricular functio n. Methods. From the 6,273 patients recruited into the Studies of Left Ventricular Dysfunction Registry (SOLVD), a subgroup of 859 patients were randomly selected, and their plasma norepinephrine, plasma renin activity, arginine vasopressin and atrial natriuretic peptide levels w ere correlated with clinical findings, New York Heart Association func tional class, left ventricular ejection fraction and drug use. Results . There was a weak but significant correlation between ejection fracti on and an increase in plasma norepinephrine (rho = -0.18, p < 0.0001), plasma renin activity (rho = -0.24, p < 0.0001) and arginine vasopres sin (rho = -0.12, p < 0.003). The only exception was atrial natriureti c peptide, which showed the best correlation to ejection fraction (rho = -0.37, p < 0.0001). Deterioration in functional class was associate d more with increases in atrial natriuretic peptide (p = 0.0003) and p lasma renin activity (p = 0.0003) and less with an increase in plasma norepinephrine. Of the clinical variables, elevated jugular venous pre ssure and third heart sound (S-3) gallop were significantly associated with increased levels of plasma norepinephrine, plasma renin activity and atrial natriuretic peptide. We then compared the relation of neur ohormones with clinical signs, functional status, ejection fraction an d drug therapy and controlled for mutual interactive effects. After ad justment, a decrease in ejection fraction was still significantly rela ted to an increase in plasma norepinephrine, plasma renin activity and atrial natriuretic peptide. In contrast, only a difference between fu nctional classes I and III/IV was associated with an increase in plasm a renin activity and atrial natriuretic peptide levels. Conclusions. N eurohumoral activation in patients with heart failure is related to se verity of left ventricular functional depression, and this relation is independent of functional class or concomitant drug therapy.