ECHOCARDIOGRAPHIC VARIABLES AS PROGNOSTIC INDICATORS AND THERAPEUTIC MONITORS IN CHRONIC CONGESTIVE-HEART-FAILURE - VETERANS AFFAIRS COOPERATIVE STUDIES V-HEFT-I AND V-HEFT-II

Background. Echocardiographic indexes of ventricular function have bec ome indispensable in clinical cardiology but have not been tested as p rognostic markers or therapeutic monitors in clinical trials. In two V eterans Administration trials on heart failure (Vasodilator-Heart Fail ure Trials I and II, V-HeFT I and II), echocardiographic variables wer e analyzed as predictors and monitors and were compared with other ind icators of cardiac performance. Methods and Results. Echocardiograms w ere recorded before randomization and at follow-up intervals. Baseline measurements of left ventricular internal diameters (LVIDd, LVIDs), w all thickness (THd, THs), radius to thickness ratios (Rd/THd, Rs/THs), and mitral E-point septal separation (EPSS) were evaluated as predict ors of mortality individually, in multivariate regression models with each other, and with nonechocardiographic predictors. Within-subject c hanges were compared between treatment groups. Cumulative survival cur ves were compared between strata formed by cut-points of EPSS and Rs/T Hs data. In Cox regression analyses, EPSS, LVIDs, and Rs/THs were sign ificant predictors of mortality. In V-HeFT I, Rd/THd was a predictor i n the presence of ejection fraction and peak oxygen uptake. In patient s with EPSS greater-than-or-equal-to 21, there was an 83% increase in mortality in the subgroup of patients with Rs/THs greater-than-or-equa l-to 2.5 compared with Rs/THs <2.5 (p=0.003), whereas there was no sta tistical difference for EPSS <21. EPSS showed improvement in patients treated with hydralazine-isosorbide dinitrate compared with placebo at 2 and 18 months and a trend toward deterioration between 36 and 66 mo nths. In V-HeFT II, there were no differences between enalapril and hy dralazine-isosorbide dinitrate groups at follow-up. Conclusions. Echoc ardiographic variables, EPSS, LVIDs, and Rs/THs were shown to be predi ctors of mortality and monitors of treatment for heart failure in clin ical trials.