Heart Failure Hospitalization Research Articles

Abstract 4137113: The Effectiveness of Cardiac Resynchronization Therapy in Patients with Cardiac Sarcoidosis: A Retrospective Analysis

Background: Cardiac sarcoidosis (CS) manifests in a wide range of clinical presentations, including conduction system abnormalities, ventricular arrhythmias, and systolic heart failure. Although cardiac resynchronization therapy (CRT) has shown efficacy in treating select nonischemic cardiomyopathy patients, its specific impact on CS patients remains less explored. This study aimed to evaluate the outcomes of CRT therapy in CS patients, focusing on implantable cardioverter defibrillator (ICD) therapies, heart failure (HF) hospitalizations and mortality. Methods: We retrospectively reviewed all patients with a clinical or histological diagnosis of CS who underwent device implantation (ICD or Permanent Pacemaker (PPM)) with or without CRT therapy at Johns Hopkins Hospital between 2004 and 2024. Baseline characteristics and echocardiographic parameters were assessed. Heart failure hospitalizations, the frequency of ATP (Anti-Tachycardia Pacing) or ICD shocks, and all-cause mortality were also evaluated as the outcomes. Results: The study included 212 patients (40.1% female, average age 52.8 ± 11.1 years). Eighty-five patients underwent CRT implantation (82 CRT-D and 3 CRT-P), whereas the rest received either an ICD or a PPM without CRT therapy. Most CRT devices (58.82%) were upgrades from an initial PPM or ICD. Over a follow-up of 6.15 ± 4.43 years, 27 (12.74%) patients were hospitalized for heart failure (HF), 86 (40.56%) experienced ATP or ICD shocks, and 17 (8.02%) died. The composite outcome was observed in 103 patients (48.5%), with no significant differences between CRT and non-CRT groups ( P = .51). Survival analysis indicated significantly reduced freedom from HF hospitalizations in the CRT group compared to non-CRT group ( P = .01). However, ATP/ICD shocks did not have a significant difference. CRT recipients showed an improvement in left ventricular ejection fraction (LVEF) from 35.3 ± 12.6% to 38.9 ± 13.6% at 6 months ( P = .01). Non-recipients showed no significant change in LVEF ( P = .43). Conclusions: Over an average six-year follow-up period, CRT upgrade does not appear to affect ATP/ICD shock and mortality in CS patients, although it is associated with significantly higher rates of heart failure (HF) hospitalizations compared to CS patients with an ICD or PPM alone. These findings underscore the complex response of CS patients to CRT, highlighting the need for further research to optimize treatment strategies within this subgroup.

Abstract 4142768: Association Between Right Ventricular-Pulmonary Arterial Coupling and Outcomes in Patients with Heart Failure with Preserved Ejection Fraction

Introduction: Right ventricle (RV)-pulmonary artery (PA) coupling reflects functional adaptation of RV to afterload. Impaired RV-PA coupling is associated with worse outcomes in patients with pulmonary hypertension. However, the association between RV-PA coupling and outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is not well established. Objective: To assess the association between RV-PA coupling and outcomes in patients with HFpEF and determine an optimal cutpoint of the TAPSE/RVSP ratio for prediction of adverse events. Methods: Participants with a diagnosis of HFpEF were enrolled at the University of Toledo Medical Center from March 2012 and were followed until August 2023. The ratio of tricuspid annular plain systolic excursion (TAPSE) to right ventricular systolic pressure (RVSP) on echocardiogram was used as a measure of RV-PA coupling. The primary endpoint was death or heart failure hospitalization. ROC analysis was performed to determine an optimal cutpoint point for TAPSE/RVSP. Cox proportional hazards regression model was used to assess the association between TAPSE/RVSP and outcomes. Results: 83 participants (age 68.69 ± 10.72, 67.5% female) with HFpEF and available echocardiogram data were enrolled in the study. The median TAPSE/RVSP was 0.41. Death or heart failure hospitalization occurred in 51 (56.6%) individuals. Using ROC curve analysis, we identified the optimal cutpoint of TAPSE/RVSP of 0.31 which had a sensitivity of 57% and specificity of 88% for predicting mortality (AUC 0.756, 0.622-0.889). TAPSE/RVSP less than 0.31 was associated with higher risk of death or heart failure (HF) hospitalization (HR=2.61, CI=1.28-5.33, p= 0.008), death (HR=3.40, CI=1.34-8.64, p= 0.01), and HF hospitalization (HR=2.45, CI=1.06-5.68, p= 0.03). Conclusion: Worse RV-PA coupling was associated with worse outcomes in individuals with HFpEF. The TAPSE/RVSP cutpoint of <0.31 had a good specificity for prediction of adverse events including death or HF hospitalization.

Abstract 4135480: Effect of Time Since Heart Failure Diagnosis or Hospitalization on the Cost-effectiveness of Dapagliflozin in Patients with Heart Failure with Mildly Reduced or Preserved Ejection Fraction

Background: Previous studies have shown dapagliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), to be a cost-effective treatment option for patients with heart failure (HF) with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF) in multiple European settings. Research question: Is the cost-effectiveness of dapagliflozin treatment in HFpEF/HFmrEF modified by either the time since HFpEF/HFmrEF diagnosis or the time since the last hospitalization for heart failure (HHF) event? Methods: A Markov cohort transition model was built for the UK setting, informed by patient-level data from the randomized, placebo-controlled DELIVER trial. The patient population was subset according to categories of time since last HHF event (including no prior HHF) and time since HF diagnosis (further subset to those with no prior HHF). For each subgroup, disease evolution was characterized by transitions among health states defined by quartiles of the Kansas City Cardiomyopathy Questionnaire Total Symptom Scale. The risk of fatal (cardiovascular and non-cardiovascular) and non-fatal events of worsening HF were modelled, adjusting for baseline characteristics and time-updating health state. Incremental costs and quality-adjusted life-years (QALYs) were calculated for each subgroup to yield incremental cost-effectiveness ratios (ICERs). Results: The lowest ICERs were observed for subgroups with the shortest time from HF diagnosis (with and without prior HHF) or last HHF event (Figure 1). Across all subgroups, the calculated ICERs were below the UK willingness-to-pay (WTP) threshold of £20,000/QALY gained. Conclusions: In patients with HFpEF/HFmrEF, the cost-effectiveness of dapagliflozin improved (via lower ICERs) in the subgroups corresponding to earliest disease (least time since an HHF event or HF diagnosis) compared with groups of later disease and potentially delayed treatment initiation. These findings suggest early optimization of HF therapy with implementation of guideline-directed medical therapy, including SGLT2is, may improve economic value.

Abstract 4135846: Cardiovascular Effectiveness of Glucagon-like Peptide-1 Receptor Agonists and Empagliflozin Combination Therapy in Adults with Type 2 Diabetes

Introduction/Background: Both empagliflozin and glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated cardiovascular (CV) benefits in clinical trials. However, few trials examined the combination of both therapies and evidence is scarce on whether the addition of empagliflozin to GLP-1RA has further CV benefits. Aim/Goal: We evaluated the risk of CV outcomes in patients with type 2 diabetes (T2D) initiating baseline GLP-1RA therapy that added empagliflozin compared to those that added sulfonylureas (SU). Methods: Using Medicare, Optum, and Marketscan data (2014-22), we identified patients with T2D aged ≥18 years initiating GLP-1RA that subsequently added either empagliflozin or SU. Follow-up began on the date of additional therapy and continued until discontinuation of either drug, a gap in insurance coverage, death, or study end. After propensity score standardized mortality ratio weighting adjusting for 98 covariates, we estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years evaluating a composite of myocardial infarction (MI) or stroke, hospitalization for heart failure (HHF), or all-cause death in the overall population and in patients with history of CV disease. Results: We identified 27,962 patients initiating GLP-1RA + empagliflozin vs 25,137 patients initiating GLP-1RA + SU. After weighting, relative to patients initiating GLP-1RA + SU, those initiating GLP-1RA + empagliflozin had lower risks of MI-stroke [HR 0.70 (0.55, 0.90); RD: -4.3 (-6.6, -2.0)], HHF in the primary hospital discharge position [HR: 0.59 (0.43, 0.81); RD: -3.9 (-5.8, -2.1)]; HHF in any discharge positions [HR: 0.84 (0.72, 0.98); RD: -7.6 (-11.6, -3.6)], and all-cause death [HR: 0.83 (0.62, 1.11); RD: -1.3 (-3.2, 0.56)]. Findings were similar but with larger RDs in patients with baseline CV disease ( Table ). Conclusion: In US clinical practice, patients with T2D initiating GLP-1RA that added empagliflozin had lower risks of MI-stroke, HHF, and death compared to adding SU, which suggests an additive CV benefit when combining GLP-1RA and empagliflozin therapies.

Abstract 4135708: Obesity and the risk of cardiac death in coronary artery disease

Background: The prevalence of obesity is increasing worldwide reaching epidemic proportions. Obesity increases the risk of coronary artery disease (CAD), but there is little prospective evidence about the effect of obesity on the risk of cardiac death in CAD patients. Aim: We aimed to investigate the effect of obesity and the risk of cardiac death in a prospective cohort of CAD patients. Methods: We have prospectively enrolled 1,946 patients with CAD (mean age 66.9±8.6, 68% male), with a mean follow-up of 8.7±2.2 years. BMI was measured at baseline and was categorized into 4 groups: 1) BMI 18.5-24.9 kg/m 2 (normal weight, reference group), 2) BMI 25-29.9 kg/m 2 (overweight), 3) BMI 30-34.9 kg/m 2 (class 1 obesity), and 4) BMI >35 kg/m 2 (class 2 obesity). The primary endpoint was cardiac death and secondary endpoints were sudden cardiac death/arrest (SCD/SCA), non-sudden cardiac death, non-cardiac death, and heart failure (HF) hospitalization. Statistical analysis was performed with Cox regression and was adjusted for age, sex, type 2 diabetes, CCS class, kidney function (eGFR), systolic and diastolic blood pressure, LDL, smoking, SYNTAX score, and left ventricle ejection fraction. Results: The prevalence of BMI 18.5-24.9 kg/m 2 was 18.5% (n=359), BMI 25-29.9 kg/m 2 was 47.8% (n=929), BMI 30-34.9 kg/m 2 was 24.0% (n=466), and BMI>35 kg/m 2 was 9.7% (n=189). During the follow-up, cardiac death occurred in 156 subjects, SCD/SCA in 75 subjects, non-sudden cardiac death in 81 subjects, and non-cardiac death in 197 subjects. BMI >35 kg/m 2 was associated with an increased trend of cardiac death (adjusted HR 1.92, 95% CI 0.92-4.01; p=0.08) and an increased risk of non-sudden cardiac death (adjusted HR 4.11, 95% CI 1.58-10.68; p=0.004) and HF hospitalization (adjusted HR 2.83, 95% CI 1.06-7-54; p=0.04), but not with SCD/SCA (adjusted HR 0.79, 95% CI 0.24-2.56; p=0.69) or noncardiac death (adjusted HR 0.85, 95% CI 0.43-1.69; p=0.64). The risk of cardiac death or secondary endpoints was not increased in patients with overweight or class 1 obesity. Conclusions: Class 2 obesity was associated with an increased risk of non-sudden cardiac death and heart failure hospitalization among CAD patients. Obesity may have adverse long-term effects on cardiac function and prognosis among CAD patients, supporting the benefit of optimal weight control therapy.

Abstract 4136911: Daily Dyadic Symptom Appraisal Dynamics During Care Transitions in Persons with Heart Failure and Their Care Partners

Background: Symptom monitoring after heart failure (HF) hospitalization is a central aspect of patient education. However, appraising symptoms can be difficult for persons with HF (PWHFs), and studies suggest family care partners (CPs) play a key supportive role. The purpose of this study is to examine dyadic HF symptom appraisal dynamics in PWHF-CP dyads during hospital-to-home transitions. Methods: We conducted a daily diary study of dyadic symptom appraisal in which PWHFs and CPs were enrolled during a HF hospitalization. Over 5 weeks, both completed daily assessments of the PWHF’s symptoms (HF Somatic Perception Scale, PROMIS Fatigue 4a). Each dyad’s appraisal dynamics were quantified using a set of N of 1 dyadic autoregressive time series models examining total symptoms, hallmark symptoms (dyspnea, edema) and nonspecific symptoms (early/subtle cluster, fatigue). Models were examined for within-dyad dynamics (within-dyad associations on the same day or on a 1-day lag). Patterns in significant dynamics across dyads were narratively described. Results: This analysis includes n=14 cohabitating dyads, all partnered. On average, PWHFs and CPs were 69.6±5.4 and 67.4±8.0 years of age. The sample was relatively gender balanced (43% of PWHFs and 64% of CPs identified as female), and primarily identified as non-Hispanic (86% of PWHFs, 93% of CPs) and White (93% of PWHFs, 86% of CPs). Most PWHFs had non-ischemic cardiomyopathy (64%) and were NYHA Class III/IV (86%), with 57% HFrEF (mean EF 37%±17%). Symptom appraisals were highly variable within and across dyads (Fig 1). Most (n=11, 79%) had significant dyadic dynamics, but dynamics across dyads varied by symptom type and time structure (Fig 2). Conclusions: The types of symptoms that HF care dyads are able to appraise together and the time structure of appraisals are variable during care transitions. Precision approaches tailored to individual dyads are needed to optimize inclusion of CPs in symptom monitoring interventions.

Abstract 4134947: Explainable Machine Learning to Predict Heart Failure Outcomes Using Exercise and Clinical Data

Background: Heart failure (HF) hospitalizations are associated with disease burden and cardiovascular mortality. International guidelines highlight cardiopulmonary testing (CPET) for risk stratification and prognosis in HF. Identifying individuals at risk could direct interventions to prevent admissions. This study uses explainable machine learning (XML) tools to identify CPET and clinical variables predictive of HF hospitalizations. Hypothesis: XML analysis of CPET parameters and clinical factors can yield accurate, patient-specific prediction of HF admission within one year. Methods: A retrospective single center review of 178 CPETs in patients referred for HF was completed. Clinical data within one year of CPET trained a boosted machine learning model (XGBoost). SHAP (Shapley Additive Explanations) explainability analysis emphasized key features for model predictions. Results: 44 (24.7%) patients with CPET were admitted for HF within one year. The model predicted this outcome with an area under the receiver operating characteristic curve (AUC) of 0.772. SHAP analysis (Figure 1) selected factors for decision making: pulmonary artery systolic pressure (PASP) via cardiac catheterization or echocardiogram; oxygen consumption at the ventilatory threshold (VO 2 at VT); O 2 pulse at rest; ventilatory efficiency (VE/VCO 2 slope); minute ventilation per oxygen consumption at maximal exercise (VE/VO 2 max) during CPET; left ventricle end diastolic volume by echocardiogram; and sodium-glucose cotransporter-2 inhibitor usage. Peak VO2, predicted VO2, predicted O2 pulse, and VE/VCO2 slope were significant, consistent with past studies (Table 1). Conclusion: Our XML analysis emphasizes PASP (partially related to high left ventricular filling pressures) and VO 2 (at ventilatory threshold) as predictive for HF hospitalization within one year of CPET testing. Studies to prospectively evaluate these highlighted factors are needed to continue exploring predictive capabilities to tailor interventions.

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 4135905: The Impact of Emergent Atrial Fibrillation in Patients With Newly Diagnosed Heart Failure and Differences in Risk Among Preserved vs. Reduced Ejection Fraction

Background: Atrial fibrillation (AF) and heart failure (HF) are associated with an increased risk of adverse events, with their diagnoses often coexisting. The impact of AF in HF needs additional study, with further delineation among HF type. Therefore, this study sought to determine the degree of AF burden among newly diagnosed HF patients and whether differences in risk exist between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) patients. Methods: Patients with new-onset HF between 2000-2019 were studied. To be included, patients had to have 1-year of follow-up, an ejection fraction (EF) measurement within 30 days of HF diagnosis, and no history of cancer. EF was used to define HFrEF (EF <40%) and HFpEF (EF > 40%). Multivariable Cox hazard regression was used to evaluate the risk of death and HF hospitalization at 1- and 3-years. Results: A total of 21,925 patients were studied with HFrEF (n=7931 [36.2%]) and HFpEF (n=13,994 [63.8%]). HFpEF patients were older (74 vs. 65 years) and more often female (53.7% vs. 33.1%). Prevalent AF was 40.5% (n=8879), being more common in HFpEF compared to HFrEF (65.2% vs. 34.8%). Among AF patients, HFpEF patients were also older (76 vs. 72 years) and more often female (52.7% vs. 30.8%) compared to HFrEF. The presence of AF was associated with an increased risk of HFpEF (OR=1.11, p=0.001). Prevalent AF was associated with an increased risk of death and follow-up HF hospitalization (Table). Death at 1-year and 3-years were similar between the HF groups (Table). However, the risk of HF hospitalization was greater among HFrEF patients (Table). Similar associations persisted when AF patients were propensity matched (Table). Conclusions: Among a newly diagnosed HF population, AF was common (40%) and was associated with an increased risk of HFpEF, death, and HF hospitalization. These results provide a rationale for aggressive management of HF and AF patients and the need for a randomized clinical trial to determine optimal therapy by ablation and 4-pillar HF therapy.

Abstract 4117731: Interleukin-1 Blockade in Patients With ST-Segment Elevation Myocardial Infarction Across the Spectrum of Coronary Artery Disease Complexity.

Background: Patients with ST-segment elevation myocardial infarction (STEMI) and complex coronary artery disease (CAD) face a poor prognosis, including increased heart failure (HF) risk. Interleukin-1 (IL-1) blockade with Anakinra inhibits the acute inflammatory response and prevent HF after STEMI, but data on its effects based on CAD complexity are lacking. Aims: To assess the effects of Anakinra in patients with STEMI, across the spectrum of CAD complexity. Methods: We performed a pooled secondary analysis of 139 patients with STEMI from three randomized clinical trials (VCUART studies) comparing Anakinra (N=84) versus placebo (N=55). Multivessel CAD was defined as the presence of at least one ≥70% stenosis in a non-culprit vessel of >2.5 mm diameter, not stented during index coronary intervention. The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery), SYNTAX II and Gensini scores were calculated, and patients were divided by the median. We evaluated a composite endpoint of new-onset HF, HF hospitalization, or all-cause death at 1-year follow-up using Kaplan-Meier survival curves, Cox regression analysis for Hazard Ratios, and calculated interactions between groups. Results: We included 139 patients with STEMI, 85 (61%) with single vessel CAD and 54 (39%) with multivessel CAD. According to the spectrum of CAD complexity, 60 (43%) presented a SYNTAX score >9, 59 (42%) a SYNTAX II score >24 and 65 (47%) a Gensini score >32. New-onset HF, HF hospitalization, or all-cause death occurred in a total of 23 patients: 7 among the 84 subjects in the Anakinra group and 16 within the 55 patients in the placebo group. We found no statistically significant interactions between CAD complexity and allocation to Anakinra or placebo for the composite endpoint (Figure). Conclusions: Among patients with STEMI, IL-1 blockade with Anakinra significantly reduced the risk of new-onset HF, HF hospitalization, or all-cause death compared to placebo, regardless of the number of vessels affected and the spectrum of CAD complexity.

Abstract 4138604: Impact of GLP-1 Agonist on the Incidence of Atrial Fibrillation in Obese Patients Following Heart Failure Hospitalization

Introduction: Atrial fibrillation (AF) in patients with heart failure (HF) is associated with increased morbidity and mortality. Glucagon-like peptide-1 (GLP-1) agonists have been shown to reduce cardiovascular risk in patients with obesity and diabetes, respectively. Meta-analysis of prospective trials looking at GLP-1 agonist use on the incidence of AF suggest benefit in patients with diabetes but is of unclear benefit in this regard for patients with obesity. Hypothesis: GLP-1 agonists reduce atrial fibrillation incidence in patients with diabetes and obesity. Aims: The goal of the study is to assess the effects of GLP-1 agonist on incidence of new AF in patients with obesity and diabetes following heart failure hospitalization. Methods: The study included consecutive patients who were admitted to an academic tertiary care center over three years with a primary diagnosis of heart failure exacerbation and no prior diagnosis of AF. The primary outcome was incidence of AF within 12 months after hospitalization. Demographic, comorbidity, echocardiography, and medications were obtained. Cox-regression analysis was performed to identify the predictors of new-onset AF following HF hospitalization. Results: Of the patients included in our study, 1668 (42.9%) have a BMI greater than or equal to 30, 574 (14.5%) have BMI greater than or equal to 40, and 2300 (58.2%) have diabetes mellitus. GLP-1 use is associated with a significantly lower incidence of AF at one year in obese patients (p=0.042; RR 0.73; 95% CI: 0.54-.99) (Figure), while in non-obese individuals, GLP-1 receptor agonist was not associated with a decreased incidence of AF (p=0.674; RR 1.08; 95% CI: 0.76-1.53). In patients with diabetes, GLP-1 receptor agonist use did not reach statistical significance for reduced AF incidence following heart failure hospitalization ( p=0.091; RR 0.80; 95% CI 0.62-1.04 ). Conclusion: GLP-1 receptor agonist use is associated with a statistically significant reduction of incidence of new atrial fibrillation at one year following hospitalization for heart failure in obese patients.

Abstract 4117397: SGLT2i And Cardio-Renal Outcomes In Type 2 Diabetes Mellitus: A Systematic Review And Meta Analysis.

Background: Diabetes Mellitus (DM) significantly impacts global health through cardiovascular and renal complications. SGLT2 inhibitors (SGLT2i) have emerged as beneficial for cardiovascular outcomes in Type 2 Diabetes Mellitus (T2DM). However, only few studies report outcomes related to renal function. Aim: This study aims to analyse the efficacy of SGLT2i on cardiorenal outcomes in adults with T2DM. Methods: A systematic review and meta-analysis, following PRISMA-2020 guidelines was conducted. We evaluated the efficacy of SGLT2i on cardiorenal outcomes in adults with T2DM. We included randomized controlled trials(RCT) and post hoc analyses that compared SGLT2i with placebo, focusing on cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalizations, and renal outcomes such as the progression of albuminuria and the decline of eGFR. Dichotomous outcomes were calculated using relative risk (RR) with 95% confidence interval (CI). Results: We identified 2753 studies, registered in PubMed(=788), Embase(n=538), WoS(n=369), Scopus(n=908), and Cochrane(n=150). We included 11 studies 6 RCT and 7 Post Hoc Analysis, sample size of 50.653 patients. Meta-analysis showed that SGLT2i improve cardiovascular outcomes such as reduced cardiovascular mortality (RR 0.84 [95% CI 0.73–0.97] p=0.02), heart failure hospitalizations (RR 0.65 [95%CI 0.54–0.77]p<0.00001), and their composites outcomes. Furthermore, renal outcomes with SGLT2i significantly improve Urinary Albumin-to-Creatinine Ratio (RR1.10 [95%CI 1.03–1.18]p=0.004), Improvement of the decline of the eGFR (RR1.08 [95%CI 1.04–1.11] p<0.00001) and progression of albuminuria (RR 0.69[95%CI 0.66–0.72]p<0.00001). Slower Doubling of serum creatinine (RR 0.71 [95% CI 0.61–0.82] p<0.00001), end-stage kidney disease (RR 0.66 [95% CI 0.53–0.83] p=0.0003). Reduced Acute Kidney Injury (RR 0.72 [95% CI 0.58–0.89] p=0.002) and renal impairment (RR 0.57 [95% CI 0.34–0.95] p=0.03). Regarding death from renal causes, we identified a 46% relative reduction in the risk in SGLT2i group, although was not statistically significant (RR 0.54 [95% CI: 0.23, 1.27] p=0.16). The observed heterogeneity across studies calls for careful application of these results to individual patients. Conclusion: SGLT2i confers notable advantages in managing cardiorenal complications in T2DM, demonstrating a reduction in cardiovascular mortality and heart failure hospitalizations and offering a nephroprotective effect.

Abstract 4132909: Hemodynamic Indices of Right Ventricular Function Differentially Predict Adverse Clinical Outcomes in Heart Failure with Preserved vs Reduced Ejection Fraction

Background: While the critical role of right ventricular dysfunction (RVD) in heart failure (HF) is increasingly recognized, the prevalence and prognostic impact of RVD across HF subtypes is poorly understood. Research Questions/Aims: We aimed to characterize differences in hemodynamic indices of RV function among patients with HF with preserved vs reduced ejection fraction (HFpEF, EF≥50% vs HFrEF, EF<50%) and to examine associations of RVD with longitudinal clinical outcomes by HF subtype. Methods: We identified patients with prevalent HF undergoing clinically indicated right heart catheterization at Massachusetts General Hospital (2005-2016). We examined three RV hemodynamic indices: right atrial to wedge pressure ratio (RA/PCWP), RV stroke work index (RVSWI), and pulmonary artery pulsatility index (PAPi). We used multivariable linear regression to assess differences in RV indices in HFpEF vs HFrEF. We then used Cox models to examine the association of each index with HF hospitalizations (HFH), major adverse cardiac events (MACE), and death, stratified by HF subtype. Models were adjusted for age, sex, BMI, hypertension, diabetes, lung disease, sleep apnea, and prior MI. Results: Of 2,062 patients (age 66 years, 33% women), 1,242 (60%) had HFrEF and 820 (40%) had HFpEF. RVD (RVSWI <450 mm Hg*ml/m 2 ) was present in 27% of HFrEF vs 21% of HFpEF patients. Those with HFpEF had higher RA/PCWP (β 0.12, SE 0.05, p=0.012) and RVSWI (β 0.22, SE 0.05, p<0.001) relative to HFrEF. Over 4.1 median years follow-up, 915 HFH, 1,066 MACE, and 1,116 death events occurred. Among those with HFrEF, lower PAPi was associated with greater risk of HFH (HR 0.84 (0.77, 0.92); p<0.001) and MACE (HR 0.88 (0.81, 0.96); p=0.003), and higher RVSWI was associated with greater risk of death (HR 1.17, (1.07, 1.27); p<0.001, Figure ). In contrast, in those with HFpEF, only higher RA/PCWP was associated with greater risk of death (HR 1.11 (1.00, 1.23); p=0.042). Conclusion: RVD occurs frequently in both HFrEF and HFpEF, and hemodynamic measures of RV function are associated with greater risk of MACE, death, and HFH. Importantly, the prognostic value of RV indices varied by HF subtype, highlighting key differences in the role of RVD in HFrEF vs HFpEF.

Abstract 4113561: Efficacy and Outcomes of Empagliflozin in Acute Coronary Syndrome Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated mortality benefits in patients with heart failure (HF). Since acute coronary syndrome (ACS) is an increasingly prevalent cardiovascular condition that often leads to HF, SGLT2i might play a role in reducing mortality in these patients. Previous randomized controlled trials (RCTs) have demonstrated inconsistent efficacy of Empagliflozin, an SGLT2i, in patients with ACS. Methods: A comprehensive systematic literature search was conducted spanning the major bibliographic databases to retrieve RCTs comparing Empagliflozin to placebo in patients with ACS. Odds ratios (OR) and mean differences (MD) with 95% confidence intervals were pooled using the DerSimonian and Laird random-effects model with statistical significance set at p<0.05. Results: 5 RCTs were included with 7229 ACS patients (3608 in the Empagliflozin group and 3621 in the placebo group). Empagliflozin treatment was not associated with a statistically significant difference in all-cause mortality [OR: 0.94; 95% CI: 0.76, 1.17; p=0.60], cardiovascular death [OR: 1.00; 95% CI: 0.79, 1.28; p=0.99], hospitalization for heart failure [OR: 0.86; 95% CI: 0.42, 1.74; p=0.67], serious adverse events [OR: 1.85; 95% CI: 0.29, 11.87; p=0.51], LVEF on follow-up [MD: 4.35; 95% CI: -4.52, 13.23; p=0.34], NT-ProBNP [MD: -126.02; 95% CI: -279.37, 27.32; p=0.11], estimated glomerular filtration rate [MD: 1.59; 95% CI: -1.35, 4.52; p=0.29], and HbA1c [MD: -0.17; 95% CI: -0.53, 0.20; p=0.38] compared to placebo. Conclusion: This study concludes no statistical difference in all-cause mortality, cardiovascular death, and hospitalization for heart failure with empagliflozin therapy in ACS patients compared to placebo, however, the largest study (EMPACT-MI) had a statistically significant difference in hospitalizations for HF. Further large multicentric RCTs are warranted to validate these findings.

Abstract 4129965: Efficacy of Sodium Glucose Cotransporter 2 Inhibitors In Patients With Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in patients with or without type 2 diabetes and heart failure (HF). However, studies have shown conflicting evidence regarding their efficacy in patients following acute myocardial infarction (MI). We conducted a systematic review and meta-analysis to synthesize the available evidence regarding the effectiveness of SGLT2 inhibitors in MI. Methods: A systematic literature search was conducted using PubMed/MEDLINE, the Cochrane Library, and Embase databases to identify randomized controlled trials (RCTs) that compared clinical outcomes of SGLT2 inhibitors with placebo following MI. We conducted the statistical analysis using RevMan, version 5.4, and pooled risk ratios (RRs) along the corresponding 95% confidence interval (CI) for all outcomes. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Results: Five RCTs reporting data for 11,211 patients were included in our study. Our pooled analysis showed that SGLT2 inhibitors significantly reduced the risk of hospitalizations for heart failure (HHF) (RR = 0.76, 95% CI: 0.61-0.88, p = 0.001; high certainty). In terms of absolute effects, this translated to 12 fewer HHF per 1,000 patients who received SGLT2 inhibitors compared with the placebo (absolute risk difference 12 (95% CI 17 to 5) fewer per 1000 patients) in patients with MI. However, the risk of all-cause mortality (RR = 1.05, 95% CI: 0.78-1.41, p = 0.76; high certainty), cardiovascular (CV) mortality (RR = 1.04, 95% CI = 0.84-1.29, p = 0.73; high certainty), and all-cause hospitalizations (RR = 1.06, 95% CI: 0.96-1.17, p = 0.25; high certainty) remained comparable across the two groups. Conclusion: SGLT2 inhibitors reduce HHF without affecting all-cause mortality, CV mortality, and all-cause hospitalizations. However, further evidence is required to reach a definitive conclusion.

Abstract 4119187: Association of CMR derived Global Longitudinal Strain with adverse Outcomes in Arrhythmogenic Cardiomyopathy.

Background: Arrhythmogenic cardiomyopathy (ACM) is associated with high risk of ventricular arrhythmias (VA) and heart failure (HF). Different predictive models and diagnostic criteria include parameters related to myocardial structural abnormalities and right ventricular (RV) ejection fraction (EF). Nevertheless, the value of global longitudinal strain (GLS) ascertained from cardiac magnetic resonance (CMR) for risk-stratification in the context of ACM is unknown. Aim: We aim to study the association of low CMR-derived GLS with adverse outcomes in ACM patients. Methods: This was a retrospective cohort study of ACM patients seen at a single quaternary center. ACM diagnosis followed the modified 2010 ARVC modified task force criteria. Primary outcome was a composite of life-threatening VAs, heart transplant or HF hospitalization during follow up. We excluded patients who suffered events prior to diagnosis, and those with missing or inadequate CMR protocol. Imaging parameters were acquired by CMR including EF, GLS, and late gadolinium enhancement (LGE). Results: A total of 82 patients with suspected ACM were included, with a median age of 40 years, and 43 (52.4%) were females. Most common reason of initial visit was family history of genetic cardiomyopathy in 46 (56%), while 16 (20%) patients visited our clinic due to history of syncope. Out of 60 patients who had genetic testing, 21 (35%) had mutations of DSP gene. Left ventricular involvement (non-ischemic LV-LGE by CMR) was present in 42 (56.8%) out of 74 patients who had CMR with gadolinium. Median LVEF was 62% (56, 66), and RVEF of 53% (48, 59), both by CMR. Median LVGLS was -17.01% (-14.71, -18.43), while median RVGLS was -20.5% (-18.3, -24.4). A total of 15 (18%) patients suffered the composite endpoint during an average follow up period of 8 years. Patients who suffered the composite endpoint had significantly lower mean LVGLS (-15.04% vs -16.70%, p= 0.048), and lower average RVGLS (-18.45% vs -21.33%, p=0.035) compared to patients free from the adverse outcome. Meanwhile there was no significant difference in LVEF (60.13% vs 61.18%, p=0.67), nor in RVEF (49.13% vs 54.01%, p=0.065) between the two groups. Conclusion: Lower GLS was significantly associated with VAs and HF hospitalizations in our patient population. CMR derived GLS can be used as an important prognostic parameter of adverse outcomes in patients with suspected ACM. Especially in those with LV involvement and high genetic predisposition as our cohort.

Abstract 4138611: Impact of SGLT-2 Inhibitor Use on Atrial Fibrillation Incidence Following Heart Failure Hospitalization

Introduction: The development of atrial fibrillation (AF) in patients with heart failure (HF) is associated with increased morbidity and mortality. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have demonstrated cardiovascular benefit in patients with both preserved and reduced ejection fractions. Meta analysis of prospective trials suggest reduced incidence and burden of atrial fibrillation in patients taking SGLT-2 inhibitors, though this has not been specifically addressed in prospective trials. Hypothesis: SGLT-2 inhibitors reduce the incidence of atrial fibrillation in patients with heart failure. Aim: The goal of the study is to assess the impact of SGLT-2 inhibitor on the incidence of atrial fibrillation following heart failure hospitalization. Methods: The study included consecutive patients who were admitted to an academic tertiary care center over a 3 year time period with a primary diagnosis of heart failure exacerbation and no prior diagnosis of AF. The primary outcome was development of AF within 12 months after hospitalization. Demographic, comorbidity, echocardiographic data, and medications were obtained. Cox-regression analysis was performed to identify the predictors of new-onset AF after HF hospitalization. Results: Among the 3,953 patients included in our study, 704 (17.8%) patients were prescribed SGLT-2 inhibitors. Of those taking SGLT-2 inhibitors, 559 (79.4%) patients had diabetes. SGLT-2 inhibitor use is associated with significant reduction of AF at one year ( p<0.001; RR 0.65; 95% CI: 0.51-.81 ). This finding was consistent across patients with reduced ejection fractions (EF<50%) ( p=0.001; RR 0.56; 95% CI: 0.40-.80 ) and preserved ejection fraction (EF>50%)( p=0.001; RR 0.58; 95% CI: 0.42-0.80 ). Conclusion: In patients with reduced ejection fraction and preserved ejection fraction heart failure, use of an SGLT-2 inhibitor is associated with a statistically significant lower risk of new-onset atrial fibrillation at one year following HF hospitalization.

Abstract 4127562: Age, Adiposity-Related Anthropometrics, and Clinical Outcomes in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: A Participant-Level Pooled Analysis of Randomized Trials

Background: Age has been shown to modify the population-level association between body mass index (BMI) and mortality. However, whether age modifies the association between adiposity-related anthropometrics and adverse outcomes in heart failure (HF) populations has not been systematically explored. Methods: In this participant-level pooled analysis of five international, multicenter, randomized-controlled trials enrolling adults with HF and either mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), the association between age and adiposity-related anthropometrics (BMI, waist circumference [WC], and waist-to-height ratio [WHtR]) and the primary composite outcome of time-to-first HF hospitalization or cardiovascular (CV) death was evaluated using multivariable adjusted Cox proportional hazards models (stratified by treatment and trial) and restricted cubic splines. Results: Among 21,606 participants in the analysis (mean age, 71±9 years; 49% female; 83% White; mean BMI, 30±6 kg/m 2 ), 5,350 (25%) were aged <65 years, 8,273 (38%) were aged 65-74 years, and 7,983 (37%) were aged ≥75 years at baseline. Older individuals were more likely to be female, have lower BMI and WC, and higher left ventricular ejection fraction. Overall, BMI, WC, and WHtR were steeply and non-linearly associated with the primary outcome ( Figure ). Age, as either a categorical or continuous variable, significantly modified the covariate-adjusted association between all anthropometrics and the primary composite outcome ( P ≤0.001 for all) ( Figure ). A J-shaped relationship, characterized by higher incidence of the primary outcome with lower anthropometric values, was observed only for BMI and was substantially attenuated among younger adults. Irrespective of the anthropometric used, increasing adiposity was most steeply associated with primary events among adults aged <65 years. Conclusions: In this pooled analysis of HFmrEF/HFpEF trials, age was a powerful modifier of the relationship between excess adiposity and HF hospitalization or CV death. An “obesity-survival paradox” – observed only for BMI – was not apparent in younger participants, who exhibited the steepest increase in the rate of clinical events with higher adiposity.

Abstract 4136873: The Role of Socioeconomic Status in the Association Between Cardiovascular Polygenic Risk Score and Cardiovascular Events

Introduction: Polygenic risk scores (PRS) provide a summation of small-effect genetic variants that predict cardiovascular (CV) disease risk. Socioeconomic status (SES) can also impact CV risk, but it is unknown whether SES modifies the effects of PRS on CV events. Hypothesis: The association between CV PRS and CV events is modified by SES. Methods: Participants without CV disease at baseline from the UK Biobank prospective cohort study were followed from recruitment (2006-2010) through 2023. We included participants with genetic data (for CV PRS) and CV risk factors assessed at baseline (hemoglobin A1c, total cholesterol, blood pressure, body mass index, physical activity, tobacco use, and sleep). The CV PRS was centered at zero and standardized to one unit variance within each ancestry group. SES was defined by tertiles of index of multiple deprivation (from housing, crime, income, education, employment, health deprivation and disability, and neighborhood environment). The primary outcome was CV events (myocardial infarction, heart failure hospitalization, stroke, or death). Using Cox proportional hazard models, we estimated the total effect of PRS on CV events, tested for interaction of SES in the association between PRS and CV events, and estimated the direct effect of PRS on CV events by adjusting for age, sex, CV risk factors, and SES. Results: There were 201,374 participants (mean age 55.9 (± 8.1), 53.4% female). CV events occurred in 21,916 (10.9%) participants: 5,754 (2.9 %) myocardial infarctions, 4,061 (2.0%) strokes, 4,312 (2.1%) heart failure hospitalizations, and 12,782 (6.4%) deaths. Each unit of PRS was associated with 1.17 times the risk of CV events (HR 1.17, 95%CI 1.15 to 1.18, p-value < .001, adjusted for age and sex). People with the lowest SES had 1.22 times the risk of CV events (HR 1.22; 95%CI 1.18 to 1.26; p-value <.001) and the middle SES had 1.07 times the risk of CV events (HR 1.07; 95%CI 1.03 to 1.10; p-value <.001) compared to the highest SES, adjusted for age, sex, and CV risk factors. PRS remained associated with CV events (HR 1.15, 95%CI 1.13 to 1.16, p-value<.001) after adjusting for age, sex, CV risk factors, and SES. There was no significant multiplicative interaction between SES and PRS for CV events (interaction p-value = 0.45). Conclusions: SES is associated with CV events but does not modify the effect of PRS on CV events. Genetic risk remains independently important in CV event risk beyond traditional CV risk factors and SES.

Abstract 4144585: Association of renal function with mortality and heart failure hospitalization rates after Transcatheter Mitral Valve Edge to Edge Repair

Background: Transcatheter edge to edge repair (TEER) is an established treatment for patients with symptomatic severe functional MR on optimal medical therapy or severe symptomatic primary MR and high surgical risk. Renal dysfunction is associated with adverse outcomes but the threshold at which risks rise are uncertain. Aim To determine the association of estimated glomerular filtration rate (eGFR) with adverse outcomes in patients undergoing TEER for severe symptomatic mitral regurgitation (MR) in Ontario, Canada. Methods: This was a population-based retrospective cohort study using linked administrative datasets of patients who underwent TEER in Ontario, Canada, between 2011 and 2023. The key exposure was eGFR, which was modeled using restricted cubic splines. Outcomes were 1-year mortality, cardiovascular mortality (CV) and heart failure hospitalization (HF). Cause-specific hazards regression was used to model the association between eGFR and outcomes, utilizing eGFR 30ml/min/1.73m2 as the reference value. Results: We studied 2076 patients, of whom 294 (14.2%) had eGFR <30ml/min/1.73m2 and 841 (40.5%) had eGFR 30-60ml/min/1.73m2. The incidence at one year was 16.8% for all-cause mortality, 11% for CV mortality and 14.2% for HF hospitalizations. The Figure illustrates that the predicted incidence of adverse outcomes increases with lower eGFR, with subtle differences in patterns of change in risk at lower eGFR levels such that all-cause mortality and CV mortality begin to rise rapidly at eGFR values ≤30ml/min/1.73m2, while HF hospitalization increases linearly at eGFR ≤50ml/min/1.73m2. Conclusions: There was a progressive increase in all-cause, CV mortality and HF hospitalization after TEER for patients with lower eGFR, particularly those with values <30 ml/min/1.73m2. This data can inform patient discussions and guide post-procedural follow-up.