title: Contractile state is the major determinant of functional outcome in patients with left ventricular dysfunction treated with enalapril.
abstract: Large-scale drug trials have focused primarily on mortality and morbidity and less on the functional state of the myocardium. A model was developed to assess myocardial contractile state in patients with left ventricular (LV) dysfunction and to address the questions of differences in function between patients with and without overt heart failure, effects of enalapril, and best predictors of functional outcome. Pressure-angiographic data were obtained from 16 patients with overt heart failure and 47 without heart failure. Repeat studies were conducted in 41 patients following 1 year's treatment with enalapril or placebo. Left ventricular silhouettes were divided into 18 segments to estimate regional ejection fraction, wall stress and myocardial damage (% myocardial damage). Contractile state was assessed and ranked by ejection rate-preload-afterload relationships and by a score method based on 10 myocardial and ventricular function parameters. End-diastolic and end-systolic volumes (EDV, ESV) were significantly greater (P < 0.001), ejection fraction (EF) lower (P < 0.009), % myocardial damage greater (P < 0.008) and contractile state more depressed in patients with overt heart failure. Changes in EDV and ESV (delta placebo vs delta enalapril) were significant (delta EDV, P < 0.003; delta ESV, P < 0.014). Directional shifts in the diastolic pressure-volume relationships with enalapril or placebo depended primarily on the basal contractile state and diastolic volume range. The best single predictors of post-treatment EF were the score index (a surrogate parameter for the contractile state) and ESV. Added benefits of enalapril include the prevention of further dilatation in patients with less depressed contractile state and delay in the onset of heart failure. Asymptomatic patients with LV dysfunction should also be considered for angiotensin converting enzyme (ACE) inhibitor therapy.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: I
authors.initials: I
authors.lastname: Mirsky
authors.forename: T
authors.initials: T
authors.lastname: Aoyagi
authors.forename: T
authors.initials: T
authors.lastname: Ihara
authors.forename: C
authors.initials: C
authors.lastname: van Eyll
authors.forename: M F
authors.initials: MF
authors.lastname: Rousseau
authors.forename: H
authors.initials: H
authors.lastname: Pouleur
mesh_terms: D001794:Blood Pressure; D001810:Blood Volume; D003971:Diastole; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D005544:Forecasting; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D013318:Stroke Volume; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D004656:Enalapril