Left Ventricular Ejection Fraction and Risk of Stroke and Cardiac Events in Heart Failure

Abstract

Background and Purpose In heart failure (HF), left ventricular ejection fraction (LVEF) is inversely associated with mortality and cardiovascular (CV) outcomes. Its relationship with stroke is controversial, as is the effect of antithrombotic treatment. We studied the relationship of LVEF with stroke and CV events in HF patients, and the effect of different antithrombotic treatments. Methods In the Warfarin versus Aspirin in Reduced Ejection Fraction (WARCEF) trial, 2305 patients with systolic HF (LVEF ≤ 35%) and sinus rhythm were randomized to warfarin or aspirin and followed for 3.5±1.8 years. While no differences between treatments were observed on primary outcome (death, stroke or intracerebral hemorrhage), warfarin decreased the stroke risk. The present report compares the incidence of stroke and CV events across different LVEF and treatment subgroups. Results Baseline LVEF was inversely and linearly associated with primary outcome, mortality and its components (sudden and CV death) and HF hospitalization, but not myocardial infarction. A relationship with stroke was only observed for LVEF <15% (incidence rates: 2.04 vs. 0.95/100 pt. yrs; p=0.009), which more than doubled the adjusted stroke risk (adjusted HR: 2.125, 95% CI 1.182, 3.818; p=0.012). In warfarin-treated patients, each 5% LVEF decrement significantly increased the stroke risk (adjusted HR: 1.346, 95% CI 1.044, 1.737; p=0.022; p-value for interaction=0.04). Conclusions In patients with systolic HF and sinus rhythm, LVEF is inversely associated with death and its components, whereas an association with stroke exists for very low LVEF values. An interaction with warfarin treatment on stroke risk may exist. Clinical Trial Registration - URL:http://www.clinicaltrials.gov. Unique identifier: NCT00041938

Response by Di Tullio et al to Letter Regarding Article, “Left Ventricular Ejection Fraction and Risk of Stroke and Cardiac Events in Heart Failure: Data From the Warfarin Versus Aspirin in Reduced Ejection Fraction Trial”

“…Our recent report further refines the information on stroke risk by narrowing it to patients with especially low LVEF 5 ; this knowledge may be especially valuable in the present era, when an emphasis on individualized medicine and the wider use of newer antithrombotic agents may open the door to stroke preventive strategies targeted to individual patients.…”

Analysis of echocardiographic parameters of cardiac function in patients with acute stroke

“…Many studies have shown that LVSD with low EF is only a risk factor for stroke, although there have been reports that do not support such a correlation [23][24][25][26]. According to the WARCEF trial, only EF < 15% is associated with an increased risk of stroke (HR 2.125, 95% CI, 1.182-3.818, p = 0.012) [27].…”

Relevance of Heart Failure in Prevention, Treatment and Prognosis of Ischemic Stroke

“…Further analyses of the WARCEF study showed an increasing risk of (recurrent) stroke in patients with an increasingly reduced LVEF, reaching statistical significance only in patients with LVEF < 15 % [16]. In these patients, there was a trend towards more effective stroke prevention by using acetylsalicylic acid [17]. Due to the low event rates in the WARCEF study, this finding has to be validated in further HF studies.…”