MECHANISM OF DEATH IN HEART-FAILURE - THE VASODILATOR-HEART FAILURE TRIALS

Background. The Vasodilator-Heart Failure Trial (V-HeFT) data base pro vides information on the mechanism of death of male veterans entered i nto two trials that evaluated the effect of vasodilator therapy on sur vival in heart failure. Methods and Results. Men aged 18-75 years with heart failure were recruited at 13 Department of Veterans Affairs Med ical Centers. In V-HeFT I, 283 of 642 patients (44%) died during follo w-up (average, 2.3 years), and in V-HeFT II, 285 of 804 randomized pat ients (35.5%) died during follow-up (average, 2.5 years). Mechanism of death was established centrally using a standardized classification. In V-HeFT I, 124 of the 283 deaths (43.8%) were sudden with no worseni ng of symptoms; in V-HeFT II, 104 of the 285 deaths (36.5%) were sudde n. An average of 31.5% of the deaths (31.4% and 31.6%, respectively) i n the two trials was due to pump failure. The proportion of sudden dea ths that occurred without worsening of symptoms was similar in patient s with and without ischemic heart failure. Sudden deaths tended to occ ur earlier and pump failure deaths later in both V-HeFT studies. There was a trend for a lower percentage of cardiac deaths from pump failur e and a higher percentage from sudden death in subgroups with higher p eak exercise oxygen consumption (VO2), higher ejection fraction, and l ower plasma norepinephrine levels. The proportion of deaths that occur red suddenly was similar in placebo, prazosin, and hydralazine plus is osorbide dinitrate treatment groups but was significantly lower in the enalapril treatment group. In V-HeFT I, measures of cardiac function and VO2 predicted pump failure death and sudden death. In V-HeFT II, V O2 and cardiothoracic ratio were independent predictors of all-cause d eaths and pump failure deaths; only ejection fraction was an independe nt predictor of both pump failure and sudden death. Conclusion. Althou gh mechanistically distinct terminal events can be identified in patie nts with heart failure and physiological measurements can provide some insight into the risk of these disparate events, sudden death and pum p failure death both appear largely to be linked to the severity of ca rdiac dysfunction and symptoms. Strategies to identify individuals for selective preventive therapy are not yet practical.