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

ABSTRACT: Background Following a heart failure (HF)-decompensation, there is scarce data about sex-related prognostic differences across left ventricular ejection fraction (LVEF) status. We sought to evaluate sex-related differences in 6-month mortality risk across LVEF following admission for acute HF. Methods and Results We retrospectively evaluated 4812 patients consecutively admitted for acute HF in a multicenter registry from 3 hospitals. Study end points were all-cause, cardiovascular, and HF-related mortality at 6-month follow-up. Multivariable Cox regression models were fitted to investigate sex-related differences across LVEF. A total of 2243 (46.6%) patients were women, 2569 (53.4%) were men, and 2608 (54.2%) showed LVEF≥50%. At 6-month follow-up, 645 patients died (13.4%), being 544 (11.3%) and 416 (8.6%) cardiovascular and HF-related deaths, respectively. LVEF was not independently associated with mortality (HR, 1.02; 95% CI 0.99-1.05; P=0.135). After multivariable adjustment, we found no sex-related differences in all-cause mortality (P value for interaction=0.168). However, a significant interaction between sex and cardiovascular and HF mortality risks was found across LVEF (P value for interaction=0.030 and 0.007, respectively). Compared with men, women had a significantly lower risk of cardiovascular and HF-mortality at LVEF<25% and <43%, respectively. On the contrary, women showed a higher risk of HF-mortality at the upper extreme of LVEF (>80%). Conclusions Following an admission for acute HF, no sex-related differences were found in all-cause mortality risk. However, when compared with men, women showed a lower risk of cardiovascular and HF-mortality at the lower extreme of LVEF. On the contrary, they showed a higher risk of HF death at the upper extreme.

SUBMITTER: Santas E

PROVIDER: S-EPMC9075214 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Santas Enrique E Palau Patricia P Llácer Pau P de la Espriella Rafael R Miñana Gema G Núñez-Marín Gonzalo G Lorenzo Miguel M Heredia Raquel R Sanchis Juan J Chorro Francisco Javier FJ Bayés-Genís Antoni A Núñez Julio J

Journal of the American Heart Association 20211220 1

Background Following a heart failure (HF)-decompensation, there is scarce data about sex-related prognostic differences across left ventricular ejection fraction (LVEF) status. We sought to evaluate sex-related differences in 6-month mortality risk across LVEF following admission for acute HF. Methods and Results We retrospectively evaluated 4812 patients consecutively admitted for acute HF in a multicenter registry from 3 hospitals. Study end points were all-cause, cardiovascular, and HF-relate ...[more]

PMID: 34927464

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Project description:Aims: Evidence-based guidelines for heart failure management depend mainly on current left ventricular ejection fraction (LVEF). However, fewer studies have examined the impact of prior LVEF. Patients may enter the heart failure with midrange ejection fraction (HFmrEF) category when heart failure with preserved ejection fraction (HFpEF) deteriorates or heart failure with reduced ejection fraction (HFrEF) improves. In this study, we examined the association between change in LVEF and adverse outcomes. Methods: HFmrEF patients with at least two or more echocardiograms 3 months apart at the First Affiliated Hospital of Dalian Medical University between September 1, 2015 and November 30, 2019 were identified. According to the prior LVEF, the subjects were divided into improved group (prior LVEF < 40%), stable group (prior LVEF between 40 and 50%), and deteriorated group (prior LVEF ≥ 50%). The primary outcomes were cardiovascular death, all-cause mortality, hospitalization for worsening heart failure, and composite event of all-cause mortality or all-cause hospitalization. Results: A total of 1,168 HFmrEF patients (67.04% male, mean age 63.60 ± 12.18 years) were included. The percentages of improved, stable, and deteriorated group were 310 (26.54%), 334 (28.60%), and 524 (44.86%), respectively. After a period of follow-up, 208 patients (17.81%) died and 500 patients met the composite endpoint. The rates of all-cause mortality were 35 (11.29%), 55 (16.47%), and 118 (22.52%), and the composite outcome was 102 (32.90%), 145 (43.41%), and 253 (48.28%) for the improved, stable, and deteriorated groups, respectively. Cox regression analysis showed that the deterioration group had higher risk of cardiovascular death (HR: 1.707, 95% CI: 1.064-2.739, P = 0.027), all-cause death (HR 1.948, 95% CI 1.335-2.840, P = 0.001), and composite outcome (HR 1.379, 95% CI 1.096-1.736, P = 0.006) compared to the improvement group. The association still remained significant after fully adjusted for both all-cause mortality (HR = 1.899, 95% CI 1.247-2.893, P = 0.003) and composite outcome (HR: 1.324, 95% CI: 1.020-1.718, P = 0.035). Conclusion: HFmrEF patients are heterogeneous with three different subsets identified, each with different outcomes. Strategies for managing HFmrEF should include previously measured LVEF to allow stratification based on direction changes in LVEF to better optimize treatment.

Project description:BackgroundStatins taken for cardiovascular indications by patients with breast cancer and lymphoma during doxorubicin treatment may attenuate left ventricular ejection fraction (LVEF) decline, but the effect of statins on LVEF among patients with no cardiovascular indications is unknown.MethodsA double-blind, placebo-controlled, 24-month randomized trial of 40 mg of atorvastatin per day administered to patients with breast cancer and lymphoma receiving doxorubicin was conducted within the National Cancer Institute Community Oncology Research Program across 31 sites in the United States. At pretreatment and then 6 and 24 months after initiating doxorubicin, we assessed left ventricular (LV) volumes, strain, mass, and LVEF through cardiac magnetic resonance imaging, along with cognitive function and serum markers of inflammation. The primary outcome was the difference in 24-month LVEF between placebo and treatment groups, adjusted for pretreatment LVEF.ResultsA total of 279 participants were enrolled in the trial. Participants had a mean (±SD) age of 49±12 years; 92% were women; and 83% were White. The mean (±SD) LVEF values were 61.7±5.5% before treatment and 57.4±6.8% at 24 months in the placebo group and 62.6±6.4% before treatment and 57.7±5.6% at 24 months in the atorvastatin group. On the basis of a multiple imputed data set for missing data and adjusted for each individual's pretreatment LVEF, 24-month declines in LVEF averaged 3.3±0.6 percentage points and 3.2±0.7 percentage points, for those randomly assigned to placebo versus statins, respectively (P=0.93). Across both treatment arms, similar percentages of individuals experienced changes of more than 10 percentage points in LVEF, LV strain, LV mass, cognition, and inflammation biomarkers, including among those with greater than 90% drug compliance.ConclusionsIn patients with breast cancer and lymphoma with no existing indication for statin therapy, prospective statin administration did not affect LVEF declines 2 years after doxorubicin. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01988571.).

Project description:AimsNo therapy has shown to reduce the risk of hospitalization for heart failure across the entire range of ejection fractions seen in clinical practice. We assessed the influence of ejection fraction on the effect of the sodium-glucose cotransporter 2 inhibitor empagliflozin on heart failure outcomes.Methods and resultsA pooled analysis was performed on both the EMPEROR-Reduced and EMPEROR-Preserved trials (9718 patients; 4860 empagliflozin and 4858 placebo), and patients were grouped based on ejection fraction: <25% (n = 999), 25-34% (n = 2230), 35-44% (n = 1272), 45-54% (n = 2260), 55-64% (n = 2092), and ≥65% (n = 865). Outcomes assessed included (i) time to first hospitalization for heart failure or cardiovascular mortality, (ii) time to first heart failure hospitalization, (iii) total (first and recurrent) hospitalizations for heart failure, and (iv) health status assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ). The risk of cardiovascular death and hospitalization for heart failure declined progressively as ejection fraction increased from <25% to ≥65%. Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalization, mainly by reducing heart failure hospitalizations. Empagliflozin reduced the risk of heart failure hospitalization by ≈30% in all ejection fraction subgroups, with an attenuated effect in patients with an ejection fraction ≥65%. Hazard ratios and 95% confidence intervals were: ejection fraction <25%: 0.73 (0.55-0.96); ejection fraction 25-34%: 0.63 (0.50-0.78); ejection fraction 35-44%: 0.72 (0.52-0.98); ejection fraction 45-54%: 0.66 (0.50-0.86); ejection fraction 55-64%: 0.70 (0.53-0.92); and ejection fraction ≥65%: 1.05 (0.70-1.58). Other heart failure outcomes and measures, including KCCQ, showed a similar response pattern. Sex did not influence the responses to empagliflozin.ConclusionThe magnitude of the effect of empagliflozin on heart failure outcomes was clinically meaningful and similar in patients with ejection fractions <25% to <65%, but was attenuated in patients with an ejection fraction ≥65%.Key questionHow does ejection fraction influence the effects of empagliflozin in patients with heart failure and either a reduced or a preserved ejection fraction?Key findingThe magnitude of the effect of empagliflozin on heart failure outcomes and health status was similar in patients with ejection fractions <25% to <65%, but it was attenuated in patients with an ejection fraction ≥65%.Take home messageThe consistency of the response in patients with ejection fractions of <25% to <65% distinguishes the effects of empagliflozin from other drugs that have been evaluated across the full spectrum of ejection fractions in patients with heart failure.

Project description:Background The female preponderance in heart failure with preserved ejection fraction (HFpEF) is a distinguishing feature of this disorder, but the association of sex with degree of diastolic dysfunction and clinical outcomes among individuals with HFpEF remains unclear. Methods and Results We conducted a prospective, multicenter, observational study of patients with HFpEF (PURSUIT-HFpEF [Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction]: UMIN000021831). Between 2016 and 2019, 871 patients were enrolled from 26 hospitals (follow-up: 399±349 days). We investigated sex-related differences in diastolic dysfunction and postdischarge clinical outcomes in patients with HFpEF. The echocardiographic end point was diastolic dysfunction according to American Society of Echocardiography/European Association of Cardiovascular Imaging criteria. The clinical end point was a composite of all-cause death and heart failure readmission. Women accounted for 55.2% (481 patients) of the overall cohort. Compared with men, women were older and had lower prevalence rates of hypertension, coronary artery disease, and chronic kidney disease. Women had diastolic dysfunction more frequently than men (52.8% versus 32.0%, P<0.001). The incidence of the clinical end point did not differ between women and men (women 36.1/100 person-years versus men 30.5/100 person-years, P=0.336). Female sex was independently associated with the echocardiographic end point (adjusted odds ratio, 2.839; 95% CI, 1.884-4.278; P<0.001) and the clinical end point (adjusted hazard ratio, 1.538; 95% CI, 1.143-2.070; P=0.004). Conclusions Female sex was independently associated with the presence of diastolic dysfunction and worse clinical outcomes in a cohort of elderly patients with HFpEF. Our results suggest that a sex-specific approach is key to investigating the pathophysiology of HFpEF. Registration URL: https://upload.umin.ac.jp; Unique identifier: UMIN000021831.

Dataset Information

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

Publications

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

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