Incident Heart Failure Hospitalization Research Articles

Abstract 4114417: Polygenic Risk in Heart Failure – Evaluating the Ability of a Polygenic Risk Score to Identify Risk of Future Heart Failure Events in 60,000 Patients from 6 TIMI Randomized Trials

Background: The ability of polygenic risk scores (PRS) to predict heart failure (HF) beyond classic risk factors is unclear. Aims: To evaluate the risk of a HF PRS with incident hospitalization for HF (HHF) in patients with established cardiovascular disease. Methods: We analyzed a 59 SNP HF PRS (HERMES collaboration, Henry et al) in genotyped patients from six multinational TIMI randomized controlled trials (DECLARE, ENGAGE AF, FOURIER, PEGASUS, SAVOR, SOLID). Patients were stratified to low (quintile, Q1), intermediate (Q2-Q4), or high (Q5) genetic risk. We investigated the association of the HF PRS with incident HHF (median of 2.5 years) i) stratified by prior HF, and ii) across NTproBNP concentrations at baseline, using Cox-proportional hazard models. Results are reported as HR [95% CI], per 1-SD or with Q1 as a reference, and adjusted for ancestry (principal components 1-5), age, sex, trial, BMI, smoking, systolic BP, prior CAD, DM, AF, and eGFR. Results: In 59,906 pts (median age 66 years; 71% male; 26% prior HF), the HF PRS was associated with incident HHF (HR adj per 1-SD 1.08 [1.03, 1.13], p<0.001). Compared to low genetic risk pts, the HR adj for HHF was 1.12 [1.00, 1.26] in intermediate and 1.17 [1.02, 1.35] in high-risk pts. There were significant interactions between the HF PRS and prior HF (P int 0.001), and NTproBNP (P int 0.038), respectively. In pts without prior HF (Fig A), compared to low-risk pts, the risk was increased in high- (HR adj 1.56 [1.25, 1.94], p<0.001) and intermediate-risk pts (HR adj 1.27 [1.05, 1.54], p=0.013). In contrast, there was no significant association in pts with known HF at baseline ( Fig B ). Similarly, the HF PRS was significantly associated with HHF in pts with low but not elevated NTproBNP at baseline ( Fig C ). Conclusion: Our study confirms the role of polygenic risk for HF and demonstrates that a 59 SNP PRS can identify pts at increased risk of future HF events beyond traditional clinical factors, specifically in patients without established HF or elevated NTproBNP. These findings suggest a potential application of a HF PRS for screening and early identification of pts at increased risk for HF.

Abstract 4134974: SGLT2 Inhibitors Following Acute Myocardial Infarction: A Systematic Review and Meta-Analysis

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits in various settings. However, their impact after myocardial infarction (MI) in patients without prior heart failure remains unclear. Therefore, we conducted a meta-analysis comparing SGLT2i to placebo in post-MI patients. Methods: We systematically searched Pubmed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing SGLT2i to placebo in post-MI patients. We calculated the Risk Ratio (RR) for binary outcomes and 95% confidence intervals (CI). Statistical analysis was performed using Review Manager 5.4. A random-effects model was used for all outcomes. Heterogeneity was examined with I2 statistics. Results: We included 3 RCTs comprising 11,065 patients in this meta-analysis, where 79.5% were male with a mean age of 61.9 years old. Two studies evaluated Empaglifozin and one Dapagliflozin. There was no statistically significant difference between groups in all-cause mortality (RR 1.05; 95% CI 0.78-1.41; p= 0.76; Figure 1A) and cardiovascular mortality (RR 1.04; 95% CI 0.84-1.29; p= 0.73; Figure 1B). There was a statistically significant reduction in the incidence of heart failure hospitalization in the SGLT2i group (RR 0.73; 95% CI 0.61-0.88; p< 0.01; Figure 1C). Conclusion: Our systematic review and meta-analysis found that SGLT2i significantly reduced the incidence of heart failure hospitalization in patients following MI, without significantly affecting all-cause or cardiovascular mortality.

Machine learning for prediction of incident heart failure and heart failure hospitalisation: multi-cohort development, validation and association with clinical phenotypes

Abstract Background Delayed heart failure (HF) diagnosis is associated with adverse outcomes and costs of hospitalisation.(1,2) Whilst previous tools have been developed to predict incident HF,(3) risk of HF incidence may correlate poorly with risk of HF hospitalisation, which may be more important in targeting diagnostics. Purpose To develop and validate a novel decision support tool for prediction of incident HF and HF hospitalisation, and investigate association of score with HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Methods We developed the models (FIND-HF) in UK primary care health record data from individuals aged ≥40 years without known HF (Jan 2, 1998 to Feb 28, 2022), randomly divided into training (80%) and testing (20%) datasets. We evaluated logistic regression and supervised machine learning models for prediction of 1- and 5- year HF and HF hospitalisation risk in the testing dataset with internal bootstrap validation. Models were externally validated for HF hospitalisation in data from a Taiwanese university hospital. Association of FIND-HF score with HF phenotypes of HFpEF and HFrEF was assessed in two prospective cohorts, the MATCH registry of patients diagnosed with HFrEF and the FIND-AF cohort of individuals at higher predicted risk of atrial fibrillation who underwent echocardiography. Results Of 565 284 UK individuals (mean age 68.9 (SD 12.2) years, 49.2% women), incidence of HF and HF hospitalisation was 1.1% and 0.5% at 1-year, and 6.6% and 3.4% at 5-years, respectively. Prediction performance was superior for machine learning algorithms compared with logistic regression, with best performance for XGBoost (area under receiver operating characteristic curve (AUROC) at 1 and 5-years: 0.755 and 0.723 for incident HF, and 0.738 and 0.711 for incident HF hospitalization). On external validation in 106,026 individuals in Taiwan (mean age 64.7 (SD 10.6) years, 52.8 % women), HF hospitalisation incidence was 0.71%, and 2.46% at 1- and 5- years, respectively, and discrimination performance was excellent (AUROC at 1- and 5-years: 0.834 and 0.843). When the FIND-HF score was applied to individuals in the MATCH cohort (n = 133, mean age 69.0 (SD 11.7) years, 38.3% women) and FIND-AF cohort (n = 82, mean age 71.6 (SD 7.5) years, 50.0% women), the distribution of score to clinical phenotypes demonstrated a binomial distribution (Figure 1), and likelihood of HFpEF diagnosis correlated with the numeric score (Figure 2). Conclusions The machine learning FIND-HF decision support tool can accurately identify individuals at risk of incident HF and HF hospitalisation, to enable new approaches for early detection and prevention. The variation of score amongst high risk individuals with different HF clinical phenotypes emphasizes the distinct pathophysiological pathways but shared adverse outcome profile across the HF syndrome.Figure 1Figure 2

Relationship between chronic obstructive pulmonary disease and heart failure hospitalization in patients with atrial fibrillation: the Fushimi AF Registry

Abstract Background Chronic heart failure and chronic obstructive pulmonary disease (COPD) are both common diseases and often co-exist. Patients with COPD are at increased risk for hospitalizations due to cardiovascular diseases. However, in patients with atrial fibrillation (AF), the relationship between COPD and the risk of heart failure (HF) hospitalization remains unclear. Purpose The purpose of this study was to investigate the relationship between COPD and HF hospitalization in AF patients. Methods The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, Japan. Fushimi-ku is densely populated with a total population of 283,000 and is assumed to represent a typical urban community in Japan. We started to enroll patients from March 2011, and follow-up data were available for 4,496 patients by the end of February 2022. We compared patients with and without COPD with regard to clinical background and HF hospitalization during follow-up period. Results In this cohort, the proportion of pre-existing HF among patients with COPD was 30.1%, and the proportion of COPD among patients with pre-existing HF was 5.9%. Of 4,496 patients, 238 (5.3%) patients had COPD (COPD; the mean age 75.6 years, female 20.6%), and the remaining 4,258 patients did not (Non-COPD; the mean age 73.5 years, female 41.6%). Patients with COPD were older than those without COPD. However, the proportions of patients with pre-existing HF, previous stroke, vascular disease, cardiomyopathy, coronary artery disease (CAD), diuretic use, renal dysfunction, diabetes mellitus (DM) and hypertension were comparable. During the median follow-up period of 1,824 days, the incidence of HF hospitalization was significantly higher in COPD than in Non-COPD (COPD vs. Non-COPD; 4.85% vs. 3.01% per person-year: p<0.01). In multivariate analysis adjusted by sex, age (≥ 75 years), heart disease (combined by heart failure, vascular disease, cardiomyopathy and CAD), renal dysfunction, DM, hypertension and diuretic use, COPD was an independent risk factor for HF hospitalization (hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.15-2.07, P<0.01) (Figure 1). When we analyzed patients without pre-existing HF, the incidence of HF hospitalization was also significantly higher in COPD than in Non-COPD (COPD vs. Non-COPD; 2.87% vs. 1.75% per person-year: p=0.02). In multivariate analysis after adjusting for the same factors, COPD was an independent risk factor for HF hospitalization (HR 1.63, 95% CI 1.05-2.53, P=0.03) (Figure 2). Conclusion In patients with AF, COPD was the risk of HF hospitalization. The results were consistent in AF patients without pre-existing HF.

Long-term risk of heart failure and postoperative atrial fibrillation following noncardiac surgery: not so different from non-surgical atrial fibrillation

Abstract Background Atrial fibrillation (AF) is associated with the development of heart failure (HF). However, it is unclear if postoperative AF (POAF) after noncardiac surgery differs from non-surgical AF in terms of the risk of HF. Objectives To investigate the long-term rate of incident HF in patients developing new-onset POAF after noncardiac surgery relative to patients with non-surgical nonvalvular AF (NVAF). Methods Using Danish nationwide registries, all patients aged ≥30 years who developed POAF following noncardiac, nonobstetric surgery from 1996 to 2020 were identified. These patients were matched in a 1:3 ratio by age, sex, selected comorbidities, and year of inclusion with patients with non-surgical NVAF. The primary outcome was incident HF. Secondary outcomes were HF hospitalization and all-cause mortality. Results A total of 1,846 patients with POAF were matched with 5,538 patients with non-surgical NVAF (median age: 76 years [25th-75th percentile: 67-83 years]; 53.1% females). The median follow-up was 7.6 years. Compared with patients with non-surgical NVAF, patients with POAF did not have a significantly different rate of incident HF (2.7 versus 3.0 events per 100 person-years; HR 0.89 [95% CI, 0.78-1.03]) or HF hospitalization (2.2 versus 2.4 per 100 person-years; HR 0.88 [95% CI, 0.76-1.03]), but they had a higher rate of all-cause mortality (10.0 versus 8.7 per 100 person-years; HR 1.27 [95% CI, 1.18-1.37]) (Figure 1). Conclusions Patients with new-onset postoperative atrial fibrillation did not have a significantly different rate of incident heart failure or heart failure hospitalization, but they had a higher associated rate of all-cause mortality compared to patients with non-surgical atrial fibrillation. This finding suggests that postoperative atrial fibrillation may be regarded as non-surgical atrial fibrillation in terms of the long-term risk of heart failure. This highlights the importance of increased awareness among physicians of the risk of adverse outcomes, including heart failure, in patients with postoperative atrial fibrillation after noncardiac surgery. Closer postoperative follow-up and monitoring, as well as aggressive treatment of cardiovascular risk factors, may be warranted to reduce the risk of adverse outcomes in these patients.

Synergic interaction between coronary flow reserve and left atrial diameter as a risk factor for major adverse cardiovascular events in patients with nonobstructive coronary artery disease

Abstract Background Left atrial diameter (LAD) is one of the parameters which indicate left ventricular diastolic disorders (DD) and associated with poor prognosis. Previous studies have reported the relationship between DD and coronary microvascular dysfunction (CMD) but the impact of coexisting DD and CMD on prognosis is unknown. Methods and results This study included 330 patients who underwent intracoronary physiological assessment including CFR for suspected myocardial ischemia without significant stenosis in the epicardial coronary artery from December 2019 to March 2023. Of 330 patients (female: n=96 [29%], age: 70±11 years), 109 (33%) had CMD (CFR<2.5) and 93 (28%) had DD (LAD>40 mm). Patients were classified into 4 groups based on the cut-off values of CFR and LVMI: group 1 (no CMD nor DD n=160); group 2 (only DD, n=61); group 3 (only CMD, n=77) and group 4 (both CMD and DD, n=32). Clinical follow-up was performed for major adverse cardiovascular events (MACE) including cardiovascular death, acute coronary syndrome and hospitalization for heart failure. During a median follow-up of 715 days, the cumulative MACE-free survival rate at 2 year were 97.9%, 100.0%, 95.5% and 75.1% in groups 1 to 4. Group 4 showed significantly higher MACE rate compared with other 3 groups (hazard ratio [HR] 14.3; 95% confidence interval [CI] 3.8-53.9; p<0.001, HR 14.25; 95% CI 1.8-114.4; p=0.01 and HR 4.7; 95% CI 1.4-15.8; p=0.01 respectively). Notably, Bonferroni's multiple comparison showed that Group 4 had the highest incidence of heart failure hospitalization compared with other 3 groups (p=<0.001, p=0.002, p=0.01 respectively). Cox proportional hazards model revealed that CMD and DD had synergic interaction as a risk factor for MACE (HR 9.1; 95% CI 3.4-24.4; p<0.001). Conclusion Patients with both CMD and DD showed significantly higher risk for MACE, especially for heart failure hospitalization. The combined classification based on CFR and LAD would identify the high-risk patients for MACE.MACE-free survival curveheart failure-free survival curve

REDUCE-HF: a stronger heart go a long way

Abstract Introduction/Purpose Heart failure (HF) is a serious cardiovascular condition with a significant global health concern. The risk of heart failure rehospitalisation is high globally and locally, the 30-day HF readmission was about 32% from a local study (1). The study aims to adopt an intensive treatment strategy similar to Strong-HF trial (2) and evaluate rapid up-titration of guideline directed medical therapy (GDMT) and close follow-up will improve patients' outcomes after acute heart failure (AHF). Objectives The Reduction of Decompensation and Unnecessary Cardiac failure Emergency admissions: ambulatory Heart Failure service model (REDUCE-HF) is a non-randomised prospective study evaluating clinical outcome of patients discharged from AHF. Exclusion criteria included primary valvular disorders, end-stage renal failure and metastatic cancer. After HF discharge, eligible patients were recruited into our REDUCE-HF program irrespective of LVEF. They were subsequently managed in our ambulatory HF centre within two weeks, where intensive up-titration of GDMT and close follow-up would be proceeded. The data of our service model will be compared with our 5-year historical cohort. Primary outcome comprised of all-cause mortality and heart failure hospitalisation. Secondary outcome will be comparison of clinical and functional status at baseline and 3-month on follow up. Results Between October 2022, and December 2023, 245 patients were successfully recruited into our REDUCE-HF service model. Historical cohort of 6867 patients with primary diagnosis of acute heart failure were served as control (usual care pathway), data extracted from 2018 to 2022. Their mean age was 67.8+/-12.2 and 72.2%were male. 60% of them were HFrEF (EF<=40%) and 28% were ischaemic cardiomyopathy. The mean follow up period was 3 months. At 90 days, REDUCE-HF cohort group has shown much lower all-cause mortality than usual care group (2.5% vs 9.3%, HR 0.26, 95% CI 0.18-0.41, p<0.001). There was a much lower incidence of heart failure hospitalisation in REDUCE-HF group as compared to control (8.6% vs 13.1%, HR 0.65; 95% CI 0.55 to 0.74, p<0.01). In secondary outcome, there was significant reduction of NT-ProBNP of 45.2% (from 4229 to 2319pg/m, p<0.001), tremendous increment of 6-minute walk test (from 211 to 250m, p<0.001) and remarkable improvement of KCCQ score from 55.1 to 86.7, p<0.001. The overall LVEF was significantly increased from 39% to 44%, p<0.05. The positive outcome were attributed to good adherence to GDMT: ACEi/ARB/ARNI 91%, Betablocker 90.3%, MRA 72.4% and SGLT2i 95.5%. Conclusion The REDUCE-HF ambulatory service model has been proven effective in reducing mortality, decompensation and preventing unnecessary heart failure hospitalisation in this prospective study. By intervening proactively, this model not only enhances the quality of life but also hold promise in alleviating the burden of in-patient services on heart failure.

Exome sequencing in over 63,000 patients in TIMI trials uncovers pathogenic cardiomyopathy variant carriers with high risk for heart failure and cardiovascular death

Abstract Background Rare genetic variants predisposing to cardiomyopathy (CMP) confer increased risk for adverse events. The prevalence of CMP variants in contemporary cardiovascular (CV) trials and their association with prevalent heart failure (HF) and incident HF hospitalizations (HHF) is not established. Purpose We aimed to identify carriers of rare pathogenic/likely pathogenic (PLP) variants for dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) in well-phenotyped clinical trial cohorts and to evaluate their prognostic significance. Methods Rare variants were identified from high-quality exome sequencing data from 5 large clinical trials (ENGAGE AF-TIMI 48, SAVOR-TIMI 53, PEGASUS-TIMI 54, DECLARE-TIMI 58, FOURIER (TIMI 59)). Putatively pathogenic variants for cardiomyopathy were identified using phenotype- and gene-specific curation of protein-truncating variants and high-confidence variant classifications from ClinVar. We conducted logistic regression for prevalent disease and Cox proportional hazard models for incident HHF, both adjusted by age, sex, trial, and first 10 principal components and using those without CMP variants as the reference. Sensitivity analysis by history of HF at baseline was performed for prospective outcomes. Results In 63,700 participants, we identified 866 CMP variant carriers of which 518 identified as DCM carriers (age 65±9 yrs, male 66%), 194 HCM carriers (65.5±9 yrs, male 69%), and 125 ARVC carriers (66±9 yrs, male 77%). Out of the 518 DCM variant carriers, 402 had a PLP variant in TTN. DCM variant carriers had higher odds of history of HF (Odds ratio [OR] 1.94, 1.57-2.39, p<0.0001) whereas this was not observed for HCM variant carriers (OR 1.18, 0.85-1.65, p=0.33) or ARVC variant carriers (OR 1.23, 0.80-1.90, p=0.35). Over a mean follow-up of 2.5 years, the rate of HHF was significantly higher for DCM variant carriers (Hazard ratio [HR] 1.58, 1.14-2.20, p=0.006), HCM variant carriers (HR 2.78, 1.87-4.13, p<0.001), and ARVC variant carriers (HR 1.89, 1.02-3.53, p=0.04). These associations were, if anything, stronger in patients without HF at baseline (HR 2.06, 1.30-3.25) than in patients with HF at baseline (HR 1.48, 1.12-1.95). DCM variant carriers also had a higher rate of CV death (HR 1.50, 1.05-2.12, p=0.02), which was not observed for HCM (HR 1.10, 0.57-2.11, p=0.78) or ARVC (HR 0.35, 0.09-1.41, p=0.14) variant carriers. Conclusion In 5 contemporary CV trials, CMP variant carriers have an increased rate of HHF, while DCM variant carriers also have a higher rate of CV death. These findings motivate better identification of these high-risk individuals and the incorporation of genetic testing in CV trials.

Traditional dual-chamber right ventricular pacing versus conduction system pacing in the US medicare population

Abstract Introduction Conduction system pacing (CSP) has emerged as an alternative therapy to traditional right ventricular (RV) pacing. However, the majority of CSP studies reflect small cohorts or single-center experience. Purpose This analysis aimed to compare CSP to dual chamber (DC) RV pacing in a large, population-based cohort utilizing data from the Micra Coverage with Evidence Development (CED) study. Methods Medicare administrative claims data were used to identify patients implanted with a DC RV pacemaker. Lead placement data from Medtronic’s device registration system was used to identify patients with treated with CSP (N=6,197) using a 3830 catheter-delivered lead or DC RV (non-3830 lead, non-CSP placement) (N=16,989) at the same centers. CSP patients were stratified into left bundle branch area pacing (LBBAP) (N=4,738) and His-bundle pacing (HBP) (N=1,459). Incident heart failure hospitalizations (iHFH), all-cause mortality, complication rates and reinterventions at 6 months were analyzed. Results CSP (LBBAP and HBP) patients with a 3830 catheter-delivered lead experienced significantly lower rates of iHFH (HR: 0.70, P=0.02) and all-cause mortality at 6 months compared with DC RV patients (HR: 0.66, P<.0001) (figure). There was no difference in complications (HR: 0.89, P=0.06) or need for reintervention (HR: 0.83, P=0.08) with LBBAP compared to DC RV, though HBP patients experienced significantly higher rates of complications (HR: 1.41, P=0.001) compared to LBBAP. Conclusion Patients treated with CSP with a 3830 catheter-delivered lead experienced significant all-cause mortality and HFH benefits compared to DC RV pacing. LBBAP had lower complications compared to HBP. These real-world results in a large cohort of Medicare patients align with findings in small clinical studies demonstrating the benefits of LBBAP. Future research will focus on understanding patient selection for CSP.Figure

Postoperative atrial fibrillation following noncardiac surgery is associated with long-term heart failure: insights from a nationwide cohort

Abstract Background Atrial fibrillation (AF) is associated with the development of heart failure (HF). Whether postoperative AF (POAF) also confers a greater risk of HF is unclear. Purpose To investigate the long-term rate of incident HF in patients developing new-onset POAF after noncardiac surgery relative to patients who did not develop POAF after noncardiac surgery. Methods In this cohort study, the Danish nationwide registries were used to identify all patients aged ≥30 years who developed POAF following noncardiac, nonobstetric surgery from 1996 to 2020. These patients were matched in a 1:3 ratio by age, sex, type of surgery, selected comorbidities, and year of inclusion with patients without POAF after noncardiac surgery. The primary outcome was incident HF. Secondary outcomes were HF hospitalization and all-cause mortality. Results A total of 2,270 patients with POAF were matched with 6,810 patients without POAF (median age: 75 years [25th-75th percentile: 67-82 years]; 53.5% females). The median follow-up was 7.2 years. Compared with patients without POAF, those with POAF had a higher associated long-term rate of incident HF (2.6 versus 1.2 events per 100 person-years; HR 2.39 [95% CI 2.06-2.78]]), HF hospitalization (2.2 versus 1.0 events per 100 person-years; HR 2.33 [95% CI 1.97-2.74]), and all-cause mortality (9.8 versus 7.4 events per 100-person-years; HR 1.55 [95% CI 1.45-1.66]) (Figure 1). Conclusions Patients with new-onset postoperative atrial fibrillation following noncardiac surgery had a higher associated long-term rate of incident heart failure compared to those without postoperative atrial fibrillation following noncardiac surgery. These findings highlight the importance of increased awareness among physicians of the risk of adverse outcomes, including heart failure, in patients with postoperative atrial fibrillation after noncardiac surgery. Closer postoperative follow-up and monitoring, as well as aggressive treatment of cardiovascular risk factors, may be warranted to reduce the risk of adverse outcomes in these patients.

A U-shaped relationship between LVEF and the risk of heart failure hospitalization: a large hospital-based cohort study

Abstract Background Left ventricular ejection fraction (LVEF) is a frequently used metric for quantifying left ventricular function. Previous studies found a U-shaped relationship between LVEF and long-term survival. However, the association between the spectrum of LVEF and heart failure (HF) hospitalization remains unclear. Purpose We aim to investigate the distribution of HF hospitalizations across the spectrum of LVEF using a large hospital-based cohort. Methods Consecutive participants who underwent echocardiography (2002-2021) in a tertiary medical center in Taiwan were included. LVEF was measured by echocardiography using biplane Simpson’s method and was categorized into intervals of 5% from <20% to ≥70%. The study outcome was HF hospitalization by linking to the National Health Insurance Registry Database. Cox proportional hazards regression was used for analyses with adjustment for age, sex, hypertension, diabetes, hyperlipidemia, coronary artery disease, and history of HF. We used restricted cubic splines to demonstrate the distribution of HF hospitalizations across the spectrum of LVEF. Results 94,762 participants (age 59.7 ± 18.1, men 51.4%) were included. Adjusted hazard ratios (HR) for HF hospitalizations showed a U-shaped relationship between LVEF and the risk of incident HF hospitalization with a nadir of risk at LVEF of 60-70%. (Figure) Compared with the reference group (LVEF: 60-65%), subjects with LVEF> 70% had an HR of 1.49 (95% confidence interval [CI]: 1.21-1.84), and those with LVEF of 50-55% had an HR of 1.93 (95% CI: 1.68-2.22). Similar results with a nadir at 60-70% could be observed irrespective of different age groups defined by the World Health Organization (WHO), sex, with or without hypertension or diabetes. Conclusions A U-shaped relationship between LVEF and the risk of incident HF hospitalization can be observed, with a nadir at LVEF of 60-70%. LVEF ≥ 70% may be defined as supranormal LVEF that necessitates further HF treatment.Figure

TCT-625 A Lower Ratio of Regurgitant Volume to Left Atrium Volume Is Associated With a Higher Incidence of Heart Failure Hospitalization in Patients With Ventricular Functional Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair: Insights From the OCEAN-Mitral Registry

TCT-625 A Lower Ratio of Regurgitant Volume to Left Atrium Volume Is Associated With a Higher Incidence of Heart Failure Hospitalization in Patients With Ventricular Functional Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair: Insights From the OCEAN-Mitral Registry

Addition of Ezetimibe to Intensive Lipid-Lowering Therapy Is Associated With a Lower Incidence of Heart Failure in Patients With Acute Coronary Syndrome.

This study investigated whether intensive lipid-lowering therapy with pitavastatin and ezetimibe lowers the incidence of heart failure (HF) events in patients with acute coronary syndrome (ACS). In the HIJ-PROPER study, 1,734 patients with ACS were randomly assigned to either pitavastatin plus ezetimibe therapy (n=864) or pitavastatin monotherapy (n=857). We examined the incidence of HF between these 2 groups over a 3.9-year period after ACS. The primary endpoint of the study was hospitalization for HF. The mean low-density lipoprotein cholesterol levels during the follow-up period were 65.1 mg/dL in the pitavastatin plus ezetimibe group and 84.6 mg/dL in the pitavastatin monotherapy group. The incidence of HF hospitalization was significantly lower in the pitavastatin plus ezetimibe group than in the pitavastatin monotherapy group (19 [2.2%] vs. 40 [4.7%] patients; hazard ratio 0.47, 95% confidence interval 0.27-0.81; P<0.005). This trend was consistent after multivariable analysis using multiple models. Intensive lipid-lowering therapy with pitavastatin and ezetimibe is associated with a lower incidence of hospitalization for HF in patients with ACS.

Trajectory of Cognitive Decline After Incident Heart Failure Hospitalization: Findings From the REGARDS Study.

Cognitive impairment is common among adults with heart failure (HF) and associated with poor outcomes. However, less is known about the trajectory of cognitive decline after a first HF hospitalization. We examined the rate of cognitive decline among adults with incident HF hospitalization compared with those without HF hospitalization. The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a prospective longitudinal study of 23 894 participants aged ≥45 years free of HF at baseline. HF hospitalization was expert adjudicated. Changes in global cognitive function (primary outcome) were assessed with the Six-Item Screener (range, 0-6). Secondary outcomes included change in Word List Learning (range, 0-30), Word List Delayed Recall (WLD; range, 0-10), and Animal Fluency Test (range, 0+). Segmented linear mixed-effects regression models were used. Over 5 years, mean scores across all 4 cognitive tests declined for all participants regardless of HF status. Those with incident HF hospitalization experienced faster declines in the Six-Item Screener versus those who were HF free (difference, -0.031 [95% CI, -0.047 to -0.016]; P<0.001), a finding that persisted in fully adjusted models. Those with incident HF hospitalization did not experience faster declines in Word List Learning, Word List Delayed Recall, or Animal Fluency Test scores compared with those without HF hospitalization. Participants with hospitalization for HF with preserved, compared with reduced, ejection fraction had faster decline in Animal Fluency Test. Global cognitive decline occurred faster among adults with incident HF hospitalization compared with those who remained free of HF hospitalization. This pattern was not seen for the other cognitive domains.

Metabolic dysfunction and incidence of heart failure subtypes among Black individuals: The Jackson Heart Study.

The extent to which metabolic syndrome (MetS) severity influences subclinical myocardial remodelling, heart failure (HF) incidence and subtypes, remains unclear. We assessed the association of MetS with incident HF (including ejection fraction subtypes) among Black individuals. We included 4069 Jackson Heart Study participants (mean age 54.4 years, 63.8% women, 37.2% with MetS) without HF. We categorized participants based on MetS status and MetS severity scores (based on waist circumference [MetS-Z-WC] and body mass index [MetS-Z-BMI]). We assessed the associations of MetS indices with echocardiographic parameters, biomarkers of myocardial damage (high-sensitivity cardiac troponin I [hs-cTnI] and B-type natriuretic peptide [BNP]) and incident HF hospitalizations including HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). MetS severity was associated with subclinical cardiac remodelling (assessed by echocardiographic measures and biomarkers of myocardial damage). Over a median of 12 years, 319 participants developed HF (157 HFpEF, 149 HFrEF and 13 HF of unknown type). MetS was associated with a twofold greater risk of HF (hazard ratio [HR] 2.07, 95% confidence interval [CI] 1.64-2.61). Compared to the lowest quartile (Q1) of MetS-Z-WC, the highest quartile (Q4) conferred a higher risk of HF (HR 2.35, 95% CI 1.67-3.30), with a stronger association for HFpEF (Q4 vs. Q1: HR 4.94, 95% CI 2.67-9.14) vs. HFrEF (HR 1.69, 95% CI 1.06-2.70). Metabolic syndrome severity was associated with both HF subtypes among Black individuals, highlighting the importance of optimal metabolic health for preventing HF.

Conduction system pacing associated with reduced heart failure hospitalizations and all-cause mortality compared with traditional right ventricular pacing in the Medicare population

BackgroundConduction system pacing (CSP) has emerged as an alternative therapy to traditional right ventricular (RV) pacing. However, most CSP studies reflect small cohorts or single-center experience. ObjectiveThis analysis compared CSP with dual-chamber (DC) RV pacing in a large, population-based cohort using data from the Micra Coverage with Evidence Development study. MethodsMedicare administrative claims data were used to identify patients implanted with a DC RV pacemaker. Lead placement data from Medtronic’s device registration system identified patients treated with CSP (n = 6197) using a 3830 catheter–delivered lead or DC RV (non–3830 lead, non–CSP placement; n = 16,989) at the same centers. CSP patients were stratified into left bundle branch area pacing (LBBAP; n = 4738) and His bundle pacing (HBP; n = 1459). Incident heart failure hospitalizations, all-cause mortality, complication rates, and reinterventions at 6 months were analyzed. ResultsCSP patients with a 3830 catheter–delivered lead experienced significantly lower rates of incident heart failure hospitalization (hazard ratio [HR], 0.70; P = .02) and all-cause mortality at 6 months compared with DC RV patients (HR, 0.66; P < .0001). There was no difference in chronic complications (HR, 0.97; P = .62) or need for reintervention (HR, 0.95; P = .63) with CSP compared with DC RV, although LBBAP patients experienced significantly lower rates of complications (HR, 0.71; P = .001) compared with HBP. ConclusionDC pacemaker patients treated with CSP using a 3830 catheter–delivered lead experienced significant all-cause mortality and heart failure hospitalization benefits compared with DC RV pacing. LBBAP had lower complications compared with HBP. These real-world results align with findings in small clinical studies demonstrating the benefits of CSP.

Comparison Between Heart Failure Without Left Ventricular Systolic Dysfunction and Progression to End-Stage in Hypertrophic Cardiomyopathy.

The incidence and prognostic predictors of heart failure (HF) without left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM), particularly their differences in terms of developing LVSD (progression to end-stage) or sudden cardiac death (SCD), are not fully elucidated. This study included 330 consecutive HCM patients with left ventricular ejection fraction (LVEF) ≥50%. HF hospitalization without LVSD and development of LVSD were evaluated as main outcomes. During a median follow-up of 7.3 years, the incidence of HF hospitalization without LVSD was 18.8%, which was higher than the incidence of developing LVSD (10.9%) or SCD (8.8%). Among patients who developed LVSD, only 19.4% experienced HF hospitalization without LVSD before developing LVSD. Multivariable analysis showed that predictors for HF hospitalization without LVSD (higher age, atrial fibrillation, history of HF hospitalization, and higher B-type natriuretic peptide concentrations) were different from those of developing LVSD (male sex, lower LVEF, lower left ventricular outflow tract gradient, and higher tricuspid regurgitation pressure gradient). Known risk factors for SCD did not predict either HF without LVSD or developing LVSD. In HCM with LVEF ≥50%, HF hospitalization without LVSD was more frequently observed than development of LVSD or SCD during mid-term follow-up. The overlap between HF without LVSD and developing LVSD was small (19.4%), and these 2 HF events had different predictors.

Trends in Mortality After Incident Hospitalization for Heart Failure Among Medicare Beneficiaries

Despite advances in treatment and care quality for patients hospitalized with heart failure (HF), minimal improvement in mortality has been observed after HF hospitalization since 2010. To evaluate trends in mortality rates across specific intervals after hospitalization. This cohort study evaluated a random sample of Medicare fee-for-service beneficiaries with incident HF hospitalization from January 1, 2008, to December 31, 2018. Data were analyzed from February 2023 to May 2024. Unadjusted mortality rates were calculated by dividing the number of all-cause deaths by the number of patients with incident HF hospitalization for the following periods: in-hospital, 30 days (0-30 days after hospital discharge), short term (31 days to 1 year after discharge), intermediate term (1-2 years after discharge), and long term (2-3 years after discharge). Each period was considered separately (ie, patients who died during one period were not counted in subsequent periods). Annual unadjusted and risk-adjusted mortality ratios were calculated (using logistic regression to account for differences in patient characteristics), defined as observed mortality divided by expected mortality based on 2008 rates. A total of 1 256 041 patients (mean [SD] age, 83.0 [7.6] years; 56.0% female; 86.0% White) were hospitalized with incident HF. There was a substantial decrease in the mortality ratio for the in-hospital period (unadjusted ratio, 0.77; 95% CI, 0.67-0.77; risk-adjusted ratio, 0.74; 95% CI, 0.71-0.76). For subsequent periods, mortality ratios increased through 2013 and then decreased through 2018, resulting in no reductions in unadjusted postdischarge mortality during the full study period (30-day mortality ratio, 0.94; 95% CI, 0.82-1.06; short-term mortality ratio, 1.02; 95% CI, 0.87-1.17; intermediate-term mortality ratio, 0.99; 95% CI, 0.79-1.19; and long-term mortality ratio, 0.96; 95% CI, 0.76-1.16) and small reductions in risk-adjusted postdischarge mortality during the full study period (30-day mortality ratio, 0.88; 95% CI, 0.86-0.90; short-term mortality ratio, 0.94; 95% CI, 0.94-0.95; intermediate-term mortality ratio, 0.94; 95% CI, 0.92-0.95; and long-term mortality ratio, 0.95; 95% CI, 0.93-0.96). In this study of Medicare fee-for-service beneficiaries, there was a substantial decrease in in-hospital mortality for patients hospitalized with incident HF from 2008 to 2018, but little to no reduction in mortality for subsequent periods up to 3 years after hospitalization. These results suggest opportunities to improve longitudinal outpatient care for patients with HF after hospital discharge.

Trajectory of C-Reactive Protein and Incident Heart Failure in Black Adults: The Jackson Heart Study.

Increased hsCRP (high-sensitivity C-reactive protein), a marker of inflammation, is associated with incident cardiovascular events. We aim to determine whether the baseline or trajectory of hsCRP levels over time predicts incident heart failure (HF) hospitalization. JHS (Jackson Heart Study) participants' (n=3920 Black adults) hsCRP levels were measured over 3 visits (from 2000 to 2013). We assessed the association of hsCRP at baseline (visit 1) with incident HF hospitalization using Cox proportional hazards models. Furthermore, we assessed the association of the trajectory of hsCRP over repeated measurements (visits 1-3) with incident HF using joint models. Hazard ratios are reflective of an increase in hsCRP by 1 SD on a log2 scale. We also assessed the association of change in hsCRP between visit 1 and visit 3 with Cox proportional hazards models by grouping patients by low (<2 mg/L) and high (≥2 mg/L) hsCRP levels. The 4 groups were low-to-low (referent), low-to-high, high-to-low, and high-to-high. Mean baseline age of participants was 54±13 years, and 63.8% were women. Over a median follow-up of 12 years, 308 (7.9%) participants were hospitalized with incident HF. Baseline hsCRP was not associated with incident HF (adjusted hazard ratio, 1.08 [95% CI, 0.96-1.22]). However, increasing hsCRP levels over repeated measures were associated with a higher risk of incident HF overall (adjusted hazard ratio, 1.22 [95% CI, 1.03-1.44]) and HF with preserved ejection fraction (adjusted hazard ratio, 1.30 [95% CI, 1.02-1.65]) but not HF with reduced ejection fraction (P>0.05). Furthermore, changes in hsCRP from low-to-high and high-to-low levels were associated with incident HF (P<0.05). While baseline hsCRP was not associated with incident HF, an increasing trajectory of hsCRP over time was associated with increased risk for incident HF (particularly HF with preserved ejection fraction). Temporal change in hsCRP may be an important marker of risk for incident HF with preserved ejection fraction in Black adults.

New ways of mitigating aldosterone in cardiorenal disease.

Steroidal mineralocorticoid receptor antagonists (MRAs) bind to the mineralocorticoid receptor and antagonize the effects of aldosterone, which contributes to the development and progression of cardio- and renovascular diseases. Guidelines recommend steroidal MRAs in patients with heart failure with reduced or mildly reduced ejection fraction, as they reduce morbidity and mortality. In heart failure with preserved ejection fraction, MRAs have not convincingly shown to improve prognosis. Steroidal MRAs delay the progression of chronic kidney disease, reduce proteinuria and lower blood pressure in resistant hypertension but can induce hyperkalaemia. Due to their limited selectivity to the mineralocorticoid receptor, steroidal MRAs can cause significant adverse effects, i.e. libido loss, erectile dysfunction, gynaecomastia, and amenorrhoea, leading to low rates of persistance. Against this background, new avenues for developing non-steroidal, selective (ns)MRAs and aldosterone-synthase inhibitors have been taken. Finerenone has been shown to delay the progression of diabetic nephropathy and lower the incidence of heart failure hospitalizations in patients with chronic kidney disease and diabetes compared with placebo. Finerenone has therefore been recommended by the 2023 European Society of Cardiology Guidelines for the management of diabetes in patients with type 2 diabetes and chronic kidney disease. Further randomized controlled trials assessing the safety and effectiveness of finerenone in patients with heart failure are currently ongoing. Esaxerenone provides antihypertensive effects and has been approved for the treatment of hypertension in Japan. Baxdrostat and lorundostat, novel selective aldosterone-synthase inhibitors, are currently under investigation. In phase II trials, baxdrostat and lorundostat were safe and effective in lowering blood pressure in resistant hypertension. In this review, we summarize and critically discuss the evidence for new drugs mitigating aldosterone in heart failure, hypertension, and chronic kidney disease.