Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure.

Abstract

Although past reports have identified a variety of prognostic factors in patients with severe chronic heart failure, previous studies have not evaluated the interaction of prognostic variables and drug treatment. We analyzed the association of 30 clinical, hemodynamic, and biochemical variables with survival in 203 consecutive patients with severe heart failure; all variables were assessed just before initiation of treatment with a variety of vasodilator drugs, and all patients were subsequently followed for 6 to 94 months. By regression analysis, pretreatment serum sodium concentration was the most powerful predictor of cardiovascular mortality, with hyponatremic patients having a substantially shorter median survival than did patients with a normal serum sodium concentration (164 vs 373 days, p = .006). The unfavorable prognosis for hyponatremic patients appeared to be related to the marked elevation of plasma renin activity that we noted in these individuals (10.0 + 2.0 ng/ml/hr), since hyponatremic patients fared significantly better when treated with angiotensin converting-enzyme inhibitors than when treated with vasodilator drugs that did not interfere with angiotensin LI biosynthesis (median survival 232 vs 108 days, p = .003). In contrast, there was no selective benefit of converting-enzyme inhibition on the survival of patients with a normal serum sodium concentration, in whom plasma renin activity was low (1.9 + 0.3 ng/ml/hr). This interaction between serum sodium concentration, drug treatment, and long-term outcome suggests that the renin-angiotensin system may exert a deleterious effect on the survival of some patients with chronic heart failure, which can be antagonized by converting enzyme inhibition, and provides a clinical counterpart for the similar prognostic role that has been postulated for angiotensin II in experimental preparations of heart failure. Circulation 73, No. 2, 257-267, 1986. PATIENTS with severe chronic heart failure have a highly unfavorable long-term prognosis.'" Thirty to fifty percent of patients with advanced left ventricular dysfunction who remain symptomatic on digitalis and diuretics will die within 1 year, and 60% to 80% will die within 2 years. '4 Although a variety of clinical and hemodynamic variables have been identified that correlate with mortality, it is not clear that modification of these factors by inotropic, diuretic, or vasodilator drugs alters their prognostic import. For example, patients with the most severe hemodynamic abnormali-

Prognostic factors in patients with congestive heart failure

“…Franciosa 62 found a higher mortality in patients with LV filling pressures higher than 27mmHg, systemic vascular resistance higher than 23 Wood units, and cardiac index smaller than 2.25L/min/m 2 . Some authors, however, found no significant correlation between LV filling pressures, cardiac output and mortality, even though these variables were slightly altered in those who did not survive 52,63 .…”

“…In patients in advanced stages of CHF (FC III and IV and low EF), the hemodynamic and functional factors are no longer predictors of the disease course, and the factors related to the neurohormonal system are fundamental for determining prognosis 27,52,63,67 . Several systems are activated in CHF in order to compensate for the circu-latory disorder caused by reduction of the cardiac output.…”

“…Renin-angiotensin-aldosterone system -The plasmatic activity of renin reflects the degree of activation of the RAAS 63,82 and its levels are increased in CHF, in the same proportion of disease severity 63,67,83 . Activation of the RAAS contributes directly to the deterioration of CHF 84 , as shown by clinical trials with ACEI 10,34,85,86 , whose results show improvement of clinical findings and increase of survival with these drugs.…”

“…The renin activity has a linear inverse relation with the plasmatic concentration of sodium 63,67,[87][88][89] , so that the presence of hyponatremia identifies a group of individuals with great activation of the RAAS 67 . This relation is partially due to the fact that RAAS has a great importance in the pathogenesis of the hyponatremic CHF 90 .…”

“…In multivariate analysis, however, they lost their statistical value, being surpassed by plasmatic catecholamines. Two years later, Lee and Packer 63 showed in a definitive way the prognostic value of sodium and plasmatic renin. Patients with sodium higher than 137mEq/L had a greater survival than those with mild hyponatremia (133 to 137mEq/L) or moderate to severe hyponatremia (<133mEq/L) 63,67 .…”