Increased long-term mortality in women with high left ventricular ejection fraction: data from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) long-term registry

Abstract

Aims There are significant sex-specific differences in left ventricular ejection fraction (LVEF), with a higher LVEF being observed in women. We sought to assess the clinical relevance of an increased LVEF in women and men. Methods and results A total of 4632 patients from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry (44.8% women; mean age 58.7 ± 13.2 years in men and 59.5 ± 13.3 years in women, P = 0.05), in whom LVEF was measured by cardiac computed tomography, were categorized according to LVEF (low <55%, normal 55–65%, and high >65%). The prevalence of high LVEF was similar in both sexes (33.5% in women and 32.5% in men, P = 0.46). After 6 years of follow-up, no difference in mortality was observed in patients with high LVEF in the overall cohort (P = 0.41). When data were stratified by sex, women with high LVEF died more often from any cause as compared to women with normal LVEF (8.6% vs. 7.1%, log rank P = 0.032), while an opposite trend was observed in men (5.8% vs. 6.8% in normal LVEF, log rank P = 0.89). Accordingly, a first order interaction term of male sex and high LVEF was significant (hazard ratios 0.63, 95% confidence intervals 0.41–0.98, P = 0.043) in a Cox regression model of all-cause mortality adjusted for age, cardiovascular risk factors, and severity of coronary artery disease (CAD). Conclusion Increased LVEF is highly prevalent in patients referred for evaluation of CAD and is associated with an increased risk of death in women, but not in men. Differentiating between normal and hyperdynamic left ventricles might improve risk stratification in women with CAD. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT01443637.

Sex‐Related Differences in Mortality Following Admission for Acute Heart Failure Across the Left Ventricular Ejection Fraction Spectrum

“… 31 In a large cohort of patients evaluated for coronary artery disease, women in the upper extreme of LVEF had a higher risk of death than men. 32 Our results are in line with these studies but extend them to the field of HF, reporting for the first time that women with HF and supranormal LVEF may have a higher risk of HF death than men.…”

Impaired coronary flow reserve in patients with supra-normal left ventricular ejection fraction at rest

“…The incidence of snLVEF was reported to be 22 ~ 33% in previous similar studies [ 4 , 5 ] and 11.3% in patients in intensive care units [ 3 ]. It reached 18.1% in our total cohort and accounted for a notable proportion of 11.0% in non-CVD risk populations.…”

“…Patients with resting snLVEF have recently stood out because of their worse prognosis in contrast to patients with nLVEF, even if patients without HF [ 1 , 4 , 5 ]. However, the pathogenesis has not yet been well-elucidated.…”

“…Referred to previous investigations related to snLVEF [ 5 , 25 ], the small heart and heart rate reserve (HRR, a surrogate marker of an increased sympathetic outflow) were considered in our current study. The small heart was defined if ESV at rest was less than 25 mL [ 4 ]. HR response to dipyridamole was defined as HRR ([(peak HR minus rest HR)/rest HR] * 100%) to account for baseline differences [ 5 ].…”

“…Recently, a "U" hazard ratio curve between resting left ventricular (LV) ejection fraction and prognosis has been observed in patients referred for routine clinical echocardiograms; abnormal LV ejection fraction (LVEF), not only reduced but also supra-normal LVEF (snLVEF), was correlated with adverse prognosis regardless of age, sex, or other relevant comorbidities including heart failure (HF) [1]. snLVEF is proposed as a new concept because of its newly observed long-or short-term worse outcome in patients with acute or chronic coronary syndrome with or without HF and even in those without cardiac symptoms, such as old women, hypertension, tumor, sepsis, and serious anemia [1][2][3][4][5]. Nevertheless, its pathological mechanism has not been clarified, which may be related to multi-factors including aortic stiffness with increasing age, cardiomyocyte hypertrophy due to enhanced afterload, increased subclinical LV mass, and the compensatory effect of the constant hyperdynamic state due to the small heart [3,[6][7][8][9][10][11][12].…”