Rates and predictors of cardiovascular and non-cardiovascular outcomes in heart failure with preserved ejection fraction.

AIMS: The detailed sub-categories of death and hospitalization, and the impact of comorbidities on cause-specific outcomes, remain poorly understood in heart failure (HF) with preserved ejection fraction (HFpEF). We sought to evaluate rates and predictors of cardiovascular (CV) and non-CV outcomes in HFpEF. METHODS: The Karolinska-Rennes study was a bi-national prospective observational study designed to characterize HFpEF (ejection fraction ≥45%). Patients were followed for cause-specific death and hospitalization. Baseline characteristics were pre-selected based on clinical relevance and potential eligibility criteria for HFpEF trials. The associations between characteristics and cause-specific outcomes were assessed with univariable and multivariable Cox regressions. RESULTS: Five hundred thirty-nine patients [56% females; median (inter-quartile range) age 79 (72-84) years; NT-proBNP/BNP 2448 (1290-4790)/429 (229-805) ng/L] were included. Over 1196 patient-years follow-up [median (min, max) 744 days (13-1959)], there were 159 (29%) deaths (13 per 100 patient-years: CV 5.1 per 100, dominated by HF 3.9 per 100; and non-CV 5.8 per 100, dominated by cancer, 2.3 per 100). There were 723 hospitalizations in 338 patients (63%; 60 per 100 patient-years: CV 33 per 100, dominated by HF 17 per 100; and non-CV 27 per 100, dominated by lung disease 5 per 100). Higher age and natriuretic peptides, lower serum natraemia and NYHA class III-IV were independent predictors of CV death; lower serum natraemia, anaemia and stroke of non-CV death; and anaemia and lower serum natraemia of non-CV death or hospitalizations. There were no apparent predictors of CV death or hospitalization. CONCLUSIONS: In a clinical cohort hospitalized and diagnosed with HFpEF, death and hospitalization rates were roughly similar for CV and non-CV causes. CV deaths were predicted primarily by severity of HF; non-CV deaths primarily by anaemia and prior stroke. Lower serum sodium predicted both. Hospitalizations were difficult to predict.

Cause-specific death in heart failure across the ejection fraction spectrum: A comprehensive assessment of over 100 000 patients in the Swedish Heart Failure Registry.

AIM: To assess cause-specific death in patients with heart failure with preserved, mildly reduced, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF). METHODS AND RESULTS: Data were analysed from the Swedish Heart Failure Registry (SwedeHF) and the National Patient Register of patients enrolled in SwedeHF 2000-2021. Cox proportional hazards regression models were performed and adjusted for age, sex and time period. Among 100 584 patients (23% HFpEF, 23% HFmrEF, 53% HFrEF), median age (interquartile range) was 75 (66-82) and 36% were female. Of those who died within 5 years, most deaths were ascribed to cardiovascular (CV) causes across all ejection fraction (EF) categories. Within 5 years, HFpEF had higher adjusted risk of non-CV death (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.28-1.38, p < 0.001) and lower adjusted risk of CV death (HR 0.85, 95% CI 0.82-0.88, p < 0.001) compared to HFrEF. Ischaemic heart disease (IHD) and cancer were the most common causes of CV and non-CV death regardless of EF category. The incidence rate of CV death due to IHD was highest in HFrEF while incidence rates of CV death due to pulmonary vascular disease, stroke, valvular heart disease and atrial fibrillation increased with increasing EF. The incidence rates of non-CV deaths due to cancer, respiratory disease, and infections increased with increasing EF. CONCLUSION: Cardiovascular death was more common than non-CV death across all EF categories although the risk of non-CV death within 5 years was higher with increasing EF. IHD and cancer were the most common causes of CV and non-CV deaths, respectively, regardless of EF category.

Prevalence, clinical characteristics and outcomes of heart failure patients with or without isolated or combined mitral and tricuspid regurgitation: An analysis from the ESC-HFA Heart Failure Long-Term Registry.

AIM: Mitral regurgitation (MR) and tricuspid regurgitation (TR) are common in patients with heart failure (HF). The aim of this study was to investigate prevalence, clinical characteristics and outcomes of patients with or without isolated or combined MR and TR across the entire HF spectrum. METHODS AND RESULTS: The ESC-HFA EORP HF Long-Term Registry is a prospective, multicentre, observational study including patients with HF and 1-year follow-up data. Outpatients without aortic valve disease were included and stratified according to isolated or combined moderate/severe MR and TR. Among 11 298 patients, 7541 (67%) had no MR/TR, 1931 (17%) isolated MR, 616 (5.5%) isolated TR and 1210 (11%) combined MR/TR. Baseline characteristics were differently distributed across MR/TR categories. Compared to HF with reduced ejection fraction, HF with mildly reduced ejection fraction was associated with a lower risk of isolated MR (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.60-0.80), and distinctly lower risk of combined MR/TR (OR 0.51; 95% CI 0.41-0.62). HF with preserved ejection fraction (HFpEF) was associated with a distinctly lower risk of isolated MR (OR 0.42; 95% CI 0.36-0.49), and combined MR/TR (OR 0.59; 95% 0.50-0.70), but a distinctly increased risk of isolated TR (OR 1.94; 95% CI 1.61-2.33). All-cause death, cardiovascular death, HF hospitalization and combined outcomes occurred more frequently in combined MR/TR, isolated TR and isolated MR versus no MR/TR. The highest incident rates were observed in isolated TR and combined MR/TR. CONCLUSION: In a large cohort of outpatients with HF, prevalence of isolated and combined MR and TR was relatively high. Isolated TR was driven by HFpEF and was burdened by an unexpectedly poor outcome.

Prevalence, characteristics and prognostic impact of aortic valve disease in patients with heart failure and reduced, mildly reduced, and preserved ejection fraction: An analysis of the ESC Heart Failure Long-Term Registry.

AIMS: To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]). METHODS AND RESULTS: Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23-1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07-1.74) but not AR (adjusted HR 1.13, 95% CI 0.96-1.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category. CONCLUSIONS: In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category.

Long-term outcomes in heart failure with preserved ejection fraction: Predictors of cardiac and non-cardiac mortality.

AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with cardiovascular (CV) and non-CV events, but long-term risk is poorly studied. We assessed incidence and predictors of the long-term CV and non-CV events. METHODS AND RESULTS: Patients presenting with acute HF, EF ≥ 45%, and N-terminal pro-brain natriuretic peptide > 300 ng/L were enrolled in the Karolinska-Rennes study in 2007-11 and were reassessed after 4-8 weeks in a stable state. Long-term follow-up was conducted in 2018. The Fine-Gray sub-distribution hazard regression was used to detect predictors of CV and non-CV deaths, investigated separately from baseline acute presentation (demographic data only) and from the 4-8 week outpatient visit (including echocardiographic data). Of 539 patients enrolled [median age 78 (interquartile range: 72-84) years; 52% female], 397 patients were available for the long-term follow-up. Over a median follow-up time from acute presentation of 5.4 (2.1-7.9) years, 269 (68%) patients died, 128 (47%) from CV and 120 (45%) from non-CV causes. Incidence rates per 1000 patient-years were 62 [95% confidence interval (CI) 52-74] for CV and 58 (95% CI 48-69) for non-CV death. Higher age and coronary artery disease (CAD) were independent predictors of CV death, and anaemia, stroke, kidney disease, and lower body mass index (BMI) and sodium concentrations of non-CV death. From the stable 4-8 week visit, anaemia, CAD, and tricuspid regurgitation (>3.1 m/s) were independent predictors of CV death, and higher age of non-CV death. CONCLUSIONS: In patients with acute decompensated HFpEF, over 5 years of follow-up, nearly two-thirds of patients died, half from CV and the other half from non-CV causes. CAD and tricuspid regurgitation were associated with CV death. Stroke, kidney disease, lower BMI, and lower sodium were associated with non-CV death. Anaemia and higher age were associated with both outcomes. [Correction added on 24 March 2023, after first online publication: In the first sentence of the Conclusions, 'two-thirds' has been inserted before 'of patients died...' in this version.].

Predictors of long-term outcome in heart failure with preserved ejection fraction: a follow-up from the KaRen study.

AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) has poor long-term prognosis. We assessed rates and predictors of outcome 10 years after an acute episode of HF. METHODS AND RESULTS: The Karolinska-Rennes (KaRen) study enrolled HFpEF patients with acute HF, ejection fraction ≥ 45%, and N-terminal pro-brain natriuretic peptide > 300 ng/L in 2007-11. Clinical data were collected at enrolment and after 4-8 weeks including detailed echocardiography. Follow-up data were collected 10 years after study initiation, starting from 6 months after enrolment until 2018 assessed by telephone. Independent predictors of primary (all-cause mortality or HF hospitalization) and secondary (all-cause mortality) outcomes were assessed by multivariable Cox regression. Of 539 patients, long-term follow-up data were available for 397 patients [52% female; median (interquartile range) age 79 (73, 84) years]. Over a follow-up of 5.44 (2.06-7.89) years, 1, 3, 5, and 10 year mortality rates were 15%, 31%, 47%, and 74%, respectively, with an incidence rate of 130/1000 patient-years. The primary outcome was met in 84% of the population, with an incidence rate of 227/1000 patient-years. The independent predictors of the primary outcome were tricuspid regurgitation peak velocity (m/s) [hazard ratio 1.87 (1.34-2.62)], diabetes mellitus [1.75 (1.11-2.74)], and cancer [1.75 (1.01-3.03)] while female sex was associated with reduced risk [0.64 (0.41-0.98)]. CONCLUSIONS: In HFpEF, 1, 3, 5, and 10 year mortality was 15%, 31%, 47%, and 74% and mortality or first HF hospitalization was 35%, 54%, 67%, and 84%, respectively. Independent predictors of mortality or HF hospitalization were tricuspid regurgitation peak velocity, diabetes mellitus, cancer, and male sex. In clinical management of HFpEF, attention should be paid to both cardiac and non-cardiac conditions.