Influence of Ejection Fraction on Cardiovascular Outcomes in a Broad Spectrum of Heart Failure Patients

Abstract

Background-Left ventricular function is a principal determinant of cardiovascular risk in patients with heart failure. The growing number of patients with preserved systolic function heart failure underscores the importance of understanding the relationship between ejection fraction and risk. Methods and Results-We studied 7599 patients with a broad spectrum of symptomatic heart failure enrolled in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Program. All patients were randomized to candesartan at a target dose of 32 mg once daily or matching placebo and followed up for a median of 38 months. We related left ventricular ejection fraction (LVEF), measured before randomization at the sites, to cardiovascular outcomes and causes of death. Mean LVEF in patients enrolled in CHARM was 38.8Ϯ14.9% (median LVEF 36%). Patients with lower LVEF tended to have higher baseline New York Heart Association class. The hazard ratio for all-cause mortality increased by 39% for every 10% reduction in ejection fraction below 45% (hazard ratio 1.39, 95% CI 1.32 to 1.46), with adjustment for baseline covariates. All-cause mortality, cardiovascular death, and all components of cardiovascular death declined with increasing ejection fraction until an ejection fraction of 45%, after which the risk of these outcomes remained relatively stable with increasing LVEF. The absolute change in rate per 100 patient-years for each 10% reduction in LVEF was greatest for sudden death and heart failure-related death. The effect of candesartan in reducing cardiovascular outcomes was consistent across LVEF categories. Conclusions-LVEF is a powerful predictor of cardiovascular outcome in heart failure patients across a broad spectrum of ventricular function. Nevertheless, once elevated to a range above 45%, ejection fraction does not further contribute to assessment of cardiovascular risk in heart failure patients. (Circulation. 2005;112:3738-3744.)

Predicting Poor Outcomes in Heart Failure

“…To put this into context, previous investigations have shown that each 10 point decrease in ejection fraction below 45% is related to a 30% increase in death rate (HR 1.31, 95% CI, 1.24 to 1.38), after adjusting for other potent risk factors (including, for example, the New York Heart Association heart failure classification) over a median of 38 months of follow-up. 3 However, it is important to note that our findings do confirm this strong relation between ejection fraction and increasing poor outcomes. Additionally, our findings are dependent on the specific time frame of prediction (ie, 5 years) that we used; a shorter time frame may have suggested stronger predictive value for echocardiogram findings.…”

“…3 Other studies, however, have demonstrated that higher ejection fraction values are associated with worse outcomes than lower values among patients with preserved left ventricular function. 4 In this study, we examine the predictive value of echocardiogram measurements, including both ejection fraction and left ventricular wall thickness so as to further clarify these risks.…”

Cardiac CT for Assessment of Myocardial Geometry before and after Surgical Repair of Apical Left Ventricular Aneurysm

“…In this respect, there was a clear indication for left ventricular reconstruction after LV aneurysm in our study patients. In the CHARM study (The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity), which included a study population of 7599, a 10% decrease in EF (in patients with an EF < 45%) was found to be associated with a 39% higher mortality risk [23] . The STICH study (surgical treatment of ischemic heart failure) is another example of a study that found a significant increase in ejection fraction after aneurysm repair in patients with an akinetic or dyskinetic ventricle following myocardial infarction and who were investigated with regard to possible advantages of additional ventricular reconstruction versus coronary bypass alone.…”

Prognostic factors in heart failure — are they all equally important?

“…Notably, it is well recognised that correlation of those two parameters is not very strong, partly because: 1) stroke volume depends not only on LVEF but also on LV end-diastolic volume and LV loading conditions, 2) LV filling pressures are related not only to its systolic but also to its diastolic function, and 3) LVEF as a sole parameter does not fully reflect LV systolic function [3]. The association of LVEF with survival is not linear as it is most markedly expressed in patients with severely reduced LVEF; once elevated above 45% LVEF does not further contribute to the estimation of cardiovascular outcomes in HF [28].…”