Risk Of Heart Failure Research Articles

Proteomic and phosphoproteomic identified structural and functional changes in the aorta associate with age-dependent hypertension in male Sprague Dawley rats.

Guillain-Barré syndrome (GBS) and cardiovascular diseases (CVDs) have been observed to have a potential association, with GBS potentially leading to cardiovascular complications. However, these observational studies may be influenced by confounding factors. This study aimed to assess the causal relationship between GBS and CVDs, including heart failure (HF), atrial fibrillation (AF), and coronary artery disease (CAD), using a two-sample bidirectional Mendelian randomization (MR) analysis. Datasets for GBS and CVDs were retrieved from the United Kingdom Biobank and analyzed using selected instrumental variables (IVs) related to genetic variations. Sensitivity tests, including heterogeneity and horizontal pleiotropy tests, were conducted to ensure the reliability of the selected IVs. The analysis results were then visualized to illustrate the causal relationships. The study identified genetic variants as IVs for both GBS and CVDs. MR analysis revealed a significant causal effect of GBS on the increased risk of HF (Inverse variance weighted [IVW], p<0.05), but no significant causal relationship was found between GBS and AF or CAD. Similarly, no causal effect of CVDs on the occurrence of GBS was observed. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy, supporting the robustness of the results. This bidirectional MR analysis suggests a causal relationship between GBS and an increased risk of HF but not with AF or CAD, nor was a reverse causal effect of CVDs on GBS observed. These findings underscore the importance of considering cardiovascular complications, particularly HF, in the clinical management of patients with GBS in European populations.

Analysis and Prediction of Risk Factors for Heart Failure

Abstract. Heart failure is a grave and progressive illness. It is associated with multiple risk factors such as age and other possible factors. Accurately identifying and quantifying these risk factors is critical to developing personalized prevention and treatment strategies. However, it is difficult for common patients to predict heart failure without the professional diagnosis of doctors, and relying on human resources to predict heart failure is more subjective. This study proposes a method to evaluate and predict the factors related to heart failure based on multiple body indicators by using random forest algorithm. The random forest prediction model was applied to assess the correlation between multiple medical indicators such as creatinine phosphokinase (CPK), serum creatinine (SCR), ejection fraction (EF), age and heart failure. CPK was found to be the most associated with heart failure. In addition, increasing follow-up period can also effectively monitor heart failure progression in patients. In this high dimension prediction problem, the prediction effect of random forest is better, and the overall accuracy is higher. The approach used in this research is important for forecasting the risk of heart failure, enhancing the survival rates of patients, and alleviating the burden on healthcare systems.

Post-TIPS Right Atrial Pressure and Left Atrial Volume Index Predict Heart Failure and Mortality: Dual Center Experience

Background: Heart failure (HF) after Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement affects up to 20% of patients. Understanding factors associated with post-TIPS HF is critical. Cirrhotic Cardiomyopathy (CCM) is associated with adverse clinical outcomes. Aims: We aim to evaluate whether hemodynamic measurements and echocardiographic markers of CCM pre- and post-TIPS can predict post-TIPS HF and death. Methods: We performed a retrospective study of cirrhotic patients who underwent TIPS between 2010 and 2015 at two centers. Patients with cardiomyopathies other than CCM were excluded. A multivariable-adjusted time-to-event analysis assessed associations of clinical, hemodynamic, and echocardiographic parameters with post-TIPS HF and death during 2 years of follow-up. 180-day landmark analysis was used to assess association of echocardiographic changes with outcomes. Results: 360 patients met study criteria. 32 developed HF post-TIPS (8.8%). Right atrial pressure (RAP) measured intraprocedurally post-TIPS insertion was associated with increased risk for HF (adjusted HR 1.10 [1.04-1.17]), with a cut off of 22mm Hg associated with highest risk (multivariable HR 2.71, [1.22-6.02]. 92 patients died (25.5%). An increase in left atrial volume index (LAVI) within 180 days post-TIPS was associated with increased mortality (HR 1.08 [1.01-1.15]). Other echocardiographic CCM markers were not associated with HF or death. Conclusion: Increases in RAP and LAVI post-TIPS, but not CCM status, predict post-TIPS HF and death, respectively. Surveillance echocardiography may play a role in identifying those at highest risk of decompensation post-TIPS. Further prospective study of CCM and its markers in relation to TIPS outcomes is warranted.

Bidirectional Risk Modulator and Modifier Variant of Dilated and Hypertrophic Cardiomyopathy in BAG3.

The genetic factors that modulate the reduced penetrance and variable expressivity of heritable dilated cardiomyopathy (DCM) are largely unknown. BAG3 genetic variants have been implicated in both DCM and hypertrophic cardiomyopathy (HCM), nominating BAG3 as a gene that harbors potential modifier variants in DCM. To interrogate the clinical traits and diseases associated with BAG3 coding variation. This was a cross-sectional study in the Penn Medicine BioBank (PMBB) enrolling patients of the University of Pennsylvania Health System's clinical practice sites from 2014 to 2023. Whole-exome sequencing (WES) was linked to electronic health record (EHR) data to associate BAG3 coding variants with EHR phenotypes. This was a health care population-based study including individuals of European and African genetic ancestry in the PMBB with WES linked to EHR phenotypes, with replication studies in BioVU, UK Biobank, MyCode, and DCM Precision Medicine Study. Carrier status for BAG3 coding variants. Association of BAG3 coding variation with clinical diagnoses, echocardiographic traits, and longitudinal outcomes. In PMBB (n = 43 731; median [IQR] age, 65 [50-76] years; 21 907 female [50.1%]), among 30 324 European and 11 198 African individuals, the common C151R variant was associated with decreased risk for DCM (odds ratio [OR], 0.85; 95% CI, 0.78-0.92) and simultaneous increased risk for HCM (OR, 1.59; 95% CI, 1.25-2.02), which was confirmed in the replication cohorts. C151R carriers exhibited improved longitudinal outcomes compared with noncarriers as assessed by age at death (hazard ratio [HR], 0.85; 95% CI, 0.74-0.96; median [IQR] age, 71.8 [63.1-80.7] in carriers and 70.3 [61.6-79.2] in noncarriers) and heart transplant (HR, 0.81; 95% CI, 0.66-0.99; median [IQR] age, 56.7 [46.1-63.1] in carriers and 55.6 [45.2-62.9] in noncarriers). C151R was associated with reduced risk of DCM (OR, 0.42; 95% CI, 0.24-0.74) and heart failure (OR, 0.27; 95% CI, 0.14-0.50) among individuals harboring truncating TTN variants in exons with high cardiac expression (n = 358). BAG3 C151R was identified as a bidirectional modulator of risk along the DCM-HCM spectrum, as well as an important genetic modifier variant in TTN-mediated DCM. This work expands on the understanding of the etiology and penetrance of DCM, suggesting that BAG3 C151R is an important genetic modifier variant contributing to the variable expressivity of DCM, warranting further exploration of its mechanisms and of genetic modifiers in DCM more broadly.

Abstract 4137272: The Impact of Genotype in Dilated and Arrhythmogenic Cardiomyopathy: Insights from the SHaRE Registry

Background: The impact of genotype on the risk of arrhythmia and heart failure in dilated and arrhythmogenic cardiomyopathy (DCM/ACM) is not well defined. Better understanding of genetic risk factors is needed to improve patient risk stratification, management, and outcomes. Methods: In this observational study, we leveraged the international Sarcomeric Human Cardiomyopathy Registry (SHaRe) to analyze the effect of arrhythmic gene variants on clinical events in patients with DCM/ACM (excluding arrhythmogenic right ventricular cardiomyopathy). Patients were stratified by the presence of pathogenic variants in 8 genes most commonly associated with ACM (AR(+): LMNA , DSP , FLNC , RBM20 , PLN , SCN5A , DES , and TMEM43 ). We assessed for risk of clinical events including ventricular arrhythmia (VA), atrial fibrillation (AF), heart failure (HF), death, and the overall composite of any of these events. Analyses were adjusted for age at diagnosis, sex, and baseline left ventricular ejection fraction (EF). Patients were also stratified by EF ≥50% in subgroup analyses. Results: A total of 1373 genotyped adults with DCM/ACM from 6 centers were included with median follow-up of 5.5 (IQR 2.4-10.4) years. Mean diagnosis age was 48 (± 15) years, and 39.5% were female. The cohort included 185 (13.5%) AR(+) patients. AR(+) compared to genotype-negative patients (N=486, 35.4%) had increased risk of VA (HR 5.02, 95% CI 3.46-7.29) and AF (HR 3.02, 95% CI 2.20-4.10). Risk of HF (HR 2.32, 95% CI 1.55-3.49) and the overall composite (HR 2.12, 95% CI 1.68-2.67) were also increased ( Figure ). Risk of each event remained significant after adjusting for age, sex, and baseline EF ( Table ). AR(+) patients with EF ≥50% also had increased risk of VA (HR 4.56, 95% CI 2.16-9.63), AF (HR 2.94, 95% CI 1.72-5.03), and the overall composite (HR 2.15, 95% CI 1.41-3.28). Conclusions: Genetic testing enables powerful risk stratification for both arrhythmias and heart failure in DCM/ACM independent of age, sex, or EF.

Abstract 4136932: Impact of Different Socioeconomic Metrics on Heart Failure-Related Admission and Short-Term Outcomes in Maryland

Introduction: Annually, over 500,000 Americans are hospitalized due to heart failure (HF), marking it as a major contributor to morbidity and mortality. It also poses a significant financial burden and leads to considerable losses in productivity. Objective: This study investigates the predictive accuracy of different socioeconomic metrics on the risk and outcomes of HF in Maryland. Methodology: A retrospective analysis of the Maryland State Inpatient Database (2016-2020) was conducted to assess the predictive accuracy of race/ethnicity, insurance status, household median income, and neighborhood poverty level (measured by the Distressed Communities Index) on the risk of heart failure-related hospital admissions and outcomes. Multivariate logistic regression models were also used to adjust for confounders. Result: During the study period, a total of 389,220 cases of HF were reported in the Maryland SID. The majority of these patients were white (56.8%) and female (51.1%), with a median age of 73 years (interquartile range [IQR] 62-82 years). The in-hospital mortality rate was 5.1%, while rates of atrial fibrillation, cardiac arrest and prolonged hospital stay were 34.4%, 0.3%, and 48.4%, respectively. Multivariate analysis revealed a substantial area under the ROC curve (AUC) indicating good model performance: 0.88 for predicting HF, 0.64 for atrial fibrillation, 0.64 for cardiac arrest 0.57 for prolonged hospital stays, 0.63 for mortality. Subgroup analyses showed variable predictiveness by race (AUC = 0.4378), payment method (AUC = 0.5754), income quartile (AUC = 0.5202), and deprivation composite score (AUC = 0.4751). Patients with private insurance had the highest risk of stress cardiomyopathy (odds ratio [OR] = 1.98; 95% confidence interval [CI] 1.70-2.29). Socioeconomic metrics, including neighborhood distress, showed varying predictive accuracy for the HF-related admissions and selected short-term outcomes, with the highest predictive accuracy for neighborhood distress on the risk of HF (AUC = 0.50, std: 0.006), atrial fibrillation (AUC = 0.48, std: 0.0007), cardiac arrest (AUC = 0.51, std: 0.007), and prolonged hospital stays (AUC = 0.53, std: 0.0005) and mortality (AUC = 0.50, std: 0.0015). Conclusion: Neighborhood poverty level demonstrates significant predictive power for assessing the risk of HF-related hospital admissions and the short-term outcomes among Maryland residents, exceeding factors like insurance and race/ethnicity.

Abstract 4135617: Large Scale Proteomics Identifies Circulating Biomarkers Relating Atrial Fibrillation to Heart Failure: the Atherosclerosis Risk in Communities Study

Introduction: There is a bidirectional relationship between atrial fibrillation (AF) and heart failure (HF) risk. Data regarding shared and unique pathways underlying each are limited. Aims: Identify plasma proteins associated with both incident AF and HF and determine the extent to which associations with one outcome are conditional on interval occurrence of the other outcome. Methods: Among participants in the community-based Atherosclerosis Risk in Communities study free of HF and AF at study visit 5 (2011-2013), we measured 4,955 plasma proteins (SomaScan aptamer-affinity assay). We performed parallel analyses of individual protein associations with incident HF and AF using multivariable Cox regression adjusted for demographic and clinical covariates at Bonferroni significance. We then repeated the analysis for each outcome in models censoring participants with interval occurrence of the other outcome (i.e. incident AF censoring for interval HF, and vice versa). We tested associations of AF-related proteins with echocardiographic and Zio patch measures at Visit 5. Results: Among 4,118 participants included, mean age was 75±5 years, 60% were female, and 18% reported Black race. We identified 83 proteins associated with incident HF (n=355 incident events at 7 [IQR 6-8] year follow-up) and 24 with incident AF (n=517 incident events at 8 [7-9] years), of which 10 were associated with both. In models of incident HF censoring for interval AF, 63 (76%) proteins remained significantly associated with HF. In contrast, in the analysis of incident AF censoring for interval HF, only 4 (17%) proteins remained associated with AF, of which 3 were also associated with HF risk (Figure). These 4 AF-related proteins were associated with measures of LV diastolic function (LA volume, E/e’. average), LV mass index, LA function (LA reservoir, LA contraction), and supraventricular ectopy density (all p&lt;0.05). Conclusion: Nearly half of proteins reflecting AF risk also associate with HF, greater than 80% of AF-associated proteins are HF-dependent, and even those that are not correlate with measures of LV remodeling and dysfunction. These findings suggest that AF-related mechanisms among older adults are part of a wider HF syndrome.

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&lt;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&lt;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 4144573: Cardiac biomarkers, intensive lifestyle intervention, and risk of heart failure subtypes in type 2 diabetes – a post-hoc analysis of the Look AHEAD trial

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) identify subclinical heart failure (HF) in type 2 diabetes (T2D). The contribution of changes in cardiac biomarkers to HF risk, particularly HF subtypes, is unclear. Whether HF risk associated with cardiac biomarkers is modifiable with an intensive lifestyle intervention (ILI) targeting weight loss is unknown. Methods: Adults with T2D and overweight/obesity in the Look Action for Health in Diabetes (AHEAD) trial without prevalent HF were included. NT-proBNP and hs-cTnT were measured at baseline, 1- and 4-years (Roche Diagnostics). Adjusted Cox models were created to evaluate the associations of baseline, 1- and 4-year change in NT-proBNP and hs-cTnT with risk of HF with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Interaction testing was performed to evaluate heterogeneous effects of the ILI vs diabetes support and education (DSE) across baseline cardiac biomarkers. Results: Of the 3,959 participants included, 212 had incident HF (108 HFpEF, 84 HFrEF) over 12 years. Higher baseline NT-proBNP and hs-cTnT were each significantly associated with higher risk of HFpEF and HFrEF ( Table) . Increases in NT-proBNP over 1- and 4-years were significantly associated with higher risk of HFpEF and HFrEF with a similar pattern of association for hs-cTnT and HF subtypes. After accounting for risk factor changes, the association of 1- and 4-year changes in NT-proBNP, but not hs-cTnT, with risk of HF subtypes remained significant. There was a significant interaction between NT-proBNP and ILI for risk of HFpEF but not HFrEF (p-int = 0.001). The ILI reduced HFpEF risk among participants with elevated (≥125 pg/mL) but not non-elevated NT-proBNP (&lt;125 pg/mL) (ILI vs DSE HR [95% CI]: 0.48 [0.25-0.93] and 1.67 [0.94-2.94], respectively). No significant treatment group by hs-cTnT interactions were identified. Conclusions: In T2D, longitudinal changes in cardiac biomarkers, particularly NT-proBNP, are significantly associated with HF risk, independent of risk factor changes. In Look AHEAD, elevated NT-proBNP may identify individuals who are more likely to benefit from the ILI for HFpEF prevention.

Abstract 4131460: Restrictive or Liberal Blood Transfusion in Patients with Myocardial Infarction and Renal Insufficiency

Background: Chronic kidney disease (CKD) is associated with risk of myocardial infarction (MI) and anemia. Among patients with CKD and anemia who experience MI, it remains uncertain if a liberal transfusion threshold (LTT) strategy (hemoglobin cutoff [Hgb] &lt; 10 g/dL) is superior to a restrictive transfusion threshold (RTT, Hgb 7-8 g/dL) strategy. Objectives: To evaluate outcomes of those with CKD randomized to RTT vs. LTT in the Myocardial Ischemia and Transfusion (MINT) trial (NCT02981407). Methods: Among 3,495 MINT participants with non-missing creatinine (99.7%), we compared the baseline characteristics and outcomes at 30 days post-randomization of those individuals without CKD (N = 1279), CKD with eGFR 30-60 mL/min/1.73 m 2 (N = 999), CKD with eGFR &lt; 30 mL/min/1.73 m 2 (N = 802), and CKD requiring dialysis (N = 415), both overall and by randomized transfusion strategy. Interaction terms for eGFR category by treatment assignment on each outcome were assessed. Results: Individuals with CKD compared to those without CKD more frequently presented with NSTEMI (all p &lt; 0.001) and had a greater risk of all-cause death, recurrent MI, rehospitalization, and heart failure (all p &lt; 0.05). Compared to a liberal transfusion strategy, a restrictive strategy among non-dialysis dependent individuals with an eGFR &lt; 30 mL/min/1.73 m 2 was associated with an increased risk of death/recurrent MI ( Figure 1 ) and unplanned rehospitalization ( Figure 2 ). Among individuals with an eGFR 30-60 mL/min/1.73 m 2 , a restrictive strategy was associated with an increased risk of cardiac death ( Figure 1 ). No eGFR category by treatment assignment interaction terms were significant. Conclusions: In this prespecified analysis, individuals with CKD were at greater risk of death, recurrent MI, heart failure, and unplanned rehospitalization at 30 days post-randomization than those without CKD. In individuals with CKD, a restrictive transfusion strategy was associated with increased risk of adverse outcomes.

Abstract 4125252: Pre-Hematopoietic Stem Cell Transplantation Echocardiographic Indices and Post-Transplant Cardiovascular Outcomes

Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with adverse cardiovascular (CV) events including the development of heart failure (HF) and arrythmias. While transthoracic echocardiogram (TTE) is routinely obtained prior to HSCT, its role in predicting the incidence of HSCT related CV events is poorly understood. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center from 2008-2019. In this analysis, we included patients from UMHS with a baseline TTE. Data on pre-HSCT TTE parameters and post-HSCT CV outcomes were collected through manual chart review. Left ventricular (LV) function and dimensions were categorized into normal, mildly abnormal, and moderately/severely abnormal based on American Society of Echocardiography guidelines. The primary outcomes were new-onset HF and atrial fibrillation/flutter post-HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT CV risk score. Results: Of the 2071 patients (mean age at HSCT 55.5 + 12.9 years; 59.5% male) with a pre-HSCT TTE (median 25 days pre-HSCT), 116 (5.6%) and 128 (6.2%) patients experienced HF and atrial fibrillation/flutter, respectively, over a median period of 2.2 years. Greater abnormalities in left ventricular internal diameter at end-diastole (LVIDd) and end-systole (LVIDs) were linearly associated with a higher risk of HF (P-trend 0.018 and 0.004, respectively) (Table). Similarly, moderately/severely abnormal LVIDd was associated with a 2.41-fold (95% CI: 1.07, 5.43) increase in risk of atrial fibrillation/flutter (Table). Pre-HSCT ejection fraction (EF) was not associated with either endpoint. Conclusion: LV dilation, even when mild, was notably associated with increased risk of developing new HF or atrial arrythmias post-HSCT, regardless of EF. Whether evidence of LV dilation should prompt the initiation of guideline directed medical therapy to minimize the risk of incident HF warrants further study.

Abstract 4137644: Association of Prolonged QTc with Development of Heart Failure after Hematopoietic Stem Cell Transplantation

Background: Use of hematopoietic stem cell transplantation (HSCT) continues to rise in the United States, particularly in older age groups; however, HSCT is associated with various cardiovascular complications including heart failure (HF). We sought to examine whether prolonged QTc prior to HSCT was associated with the risk of HF post-HSCT. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center (RUMC) between 2008-2019. In this analysis, only patients from the UMHS site were included (n=2,435). Baseline electrocardiogram (EKG) data were recorded prior to transplant (median (IQR) 14 (3, 30) days). QTc prolongation was defined per CTCAE grading criteria as Normal (&lt;440ms), Grade 1 (440-480ms), and Grade ≥2 (&gt;480ms). The primary outcome was new-onset HF defined as a diagnosis documented by health care providers after the date of hospitalization for HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT cardiovascular risk score. Results: Of the 2,435 patients (mean age at HSCT 55±13.4 years; 59.7% male; 90.5% White), 534 (21.9%) had long QTc pre-HSCT. Of those, 440 were Grade 1 and 94 were Grade ≥2. In all, 138 HF events occurred over median period of 2.3 (1.0-5.3) years. The 5-year cumulative incidence of HF was 5.0% in patients with normal QTc, 8.4% in patients with Grade 1 QTc prolongation, and 19.0% in patients with Grade ≥2 QTc prolongation (Figure). Patients with Grade 1 and Grade ≥2 prolongation had a 1.57 (95% CI: 1.05, 2.33) and 2.71 (95% CI: 1.51, 4.86) times higher risk of HF, respectively, compared to those with normal QTc. Conclusions: In this contemporary cohort of adult HSCT patients, those with QTc prolongation prior to HSCT had a higher incidence of HF compared to normal QTc, with greater degree of prolongation associated with higher risk. These findings highlight the importance of accounting for the QTc as part of the pre-transplant cardiovascular evaluation

Abstract 4137991: Association of the 2022 AHA/ACC/HFSA Heart Failure Staging and Cardiovascular and Kidney Outcomes in Patients with Diabetes and Kidney Disease: A Secondary Analysis of the SCORED Trial

Introduction: The 2022 AHA/ACC/HFSA heart failure (HF) classification newly incorporates cardiac biomarkers to identify patients at risk of HF. Research Question: Given shared risk factors between HF and other cardiorenal events, the HF stages may also guide prognosis and management of cardiovascular (CV) and kidney-related events beyond HF. Aims: Examine the association of HF stage with CV and kidney events. Methods: SCORED was a randomized trial in diabetes with kidney disease comparing sotagliflozin (sota) v. placebo on CV death, hospitalizations for HF, and urgent HF visits. SCORED participants were grouped by HF stage post hoc . Stage A: No HF, normal cardiac biomarkers (NT-proBNP; &lt;125 pg/mL, hs-cTnT; &lt;14 ng/L) and normal cardiac structure/function by echocardiography. Stage B (pre-HF): No HF but elevated NTproBNP, hsTNT or abnormal echocardiography. Stage C/D: symptomatic HF. Endpoints of interest included the primary composite endpoint (CV death and HF-related events), major adverse CV events (MACE), and kidney-related composites (See Figure caption). Using Cox regression, we examined the association between HF stage and these endpoints, and whether the effect of sota v. placebo varied by HF stage. Results: There were 741 patients in stage A, 6560 in stage B (pre-HF) and 3283 in stage C/D (established HF). The mean NTproBNP and hs-cTnT increased with HF stage. Stepwise increases in HF stage were associated with a 2-4 fold higher incidence of the primary, MACE and kidney endpoints in the placebo group, although the incidence of the kidney-specific composite was similar in stage B and C/D (Figure). The relative risk reduction with sota v. placebo for all endpoints was similar irrespective of HF stage (p-interaction&gt;0.05), with higher absolute benefit in each HF stage (Figure). The absolute benefit for the kidney-specific endpoint was comparable for stage B and C/D. Conclusions: Increasing HF stage is associated with higher risk of HF, MACE, and kidney events, but the risk of kidney events is similar in stage B (pre-HF) and stage C/D (established HF). Sota has similar relative benefits for all endpoints, irrespective of HF stage, with a corresponding increase in absolute benefits at higher stages.

Abstract 4145812: Cardiovascular MRI-Derived Cardiac Age Acceleration is Associated with Shortened Leukocyte Telomere Length But Not Clonal Hematopoiesis of Indeterminate Potential

Introduction: Cardiac structure and function typically decline with age. Abnormal acceleration of this decline, known as cardiac age acceleration, can be estimated from MRI using deep learning. Both general and cardiac-specific mechanisms may contribute to cardiac aging. Longer telomere length in circulating leukocytes, which indicates greater cellular capacity for replication, has been associated with a lower risk of heart failure and more favorable cardiac structure and function Recent data have also suggested that longer telomeres contribute to risk of clonal hematopoiesis of indeterminate potential (CHIP), which has been linked to increased risk of atherosclerosis, heart failure and arrhythmia. Here we studied whether telomere length or CHIP status are associated with deep learning derived cardiac age acceleration. Methods: We developed a deep learning model to estimate cardiac age acceleration in 70,805 UK Biobank participants from the cardiovascular MRI (four-chamber long axis view). Of these, we identified leukocyte telomere length (LTL) in 61,554 and were able to evaluate CHIP in 61,636. In an additional 372,465 participants unrelated to those with imaging, a genome-wide association study (GWAS) was conducted for LTL, and a GWAS of cardiac age acceleration was conducted in those with imaging; using these, a two-sample Mendelian randomization (MR) was performed to identify putatively causal relationships. Results: In the 61,636 participants with both CHIP and cardiac age acceleration measurements, CHIP was not associated with cardiac age acceleration regardless of driver gene (p=0.79). In contrast, cardiac age acceleration was associated with a shorter LTL (Beta=-0.025 SD, p=5.4E-10). Shorter LTL was causally associated with cardiac age acceleration (Beta=-0.10, p=0.047). Conclusions: These data suggest that general aging mechanisms conferred by shortening telomeres may contribute to the age-associated structural and functional decline of the heart as observed with MRI. In comparison, the relationship between CHIP and cardiovascular risk may not manifest in ways that cause apparent cardiac age acceleration.

Abstract 4114276: Identification of the heterogeneity in the risk of heart failure in those with left bundle branch block pattern using artificial intelligence

Introduction: The association between left bundle branch block (LBBB) and heart failure is well-established. However, the lack of a practical risk assessment tool for patients with LBBB poses a clinical challenge to the management despite the heterogeneity of the LBBB population. Hypothesis: Artificial intelligence (AI) can extract features to stratify the risk of heart failure (HF) within the heterogeneity of LBBB. Methods: All 12-lead ECGs diagnosed with LBBB recorded from 1/1/2015 to 12/31/2019 were identified in our institution. ECG data were analyzed as 2D matrices with a shape of 12×2500. The Uniform Manifold Approximation and Projection (UMAP) was used to visualize the heterogeneity of LBBB ECG. Additionally, a 2-dimensional convolutional neural network model was trained to detect LBBB ECGs associated with past HF diagnosis. The model was then applied to ECGs from an external cohort of patients with LBBB but without a history of HF. Cumulative incidences of HF admission were compared by stratifying according to tertiles of the model output (low, intermediate and high AI score groups) Results: We identified 15,124 LBBB ECGs in our institution (training dataset) and 2,463 individuals with LBBB ECGs in the external cohort (external test dataset). The UMAP projection of the ECGs revealed distinct heterogeneity in the data ( Fig A ). This heterogeneity was not fully explained by patient demographics, ECG features, or institutions. When the external cohort was divided into 3 groups according to the tertile of AI prediction, patients with high AI scores had a higher risk of HF admission (high vs low AI score group: hazard ratio (HR), 2.10; 95% confidence interval (CI), 1.66-2.65; intermediate vs low AI score group: HR, 1.39; 95%CI, 1.08-1.78: log-rank p &lt;0.0001; Fig 1B ). This finding was unchanged after adjusting for multiple clinical characteristics and ECG parameters, including QRS duration. Conclusion: We observed significant heterogeneity in ECGs presenting LBBB, and the AI model excellently stratified the risk of heart failure admission in patients with LBBB from a single recording of 12-lead ECG, suggesting great potential for clinical utility in managing patients with LBBB.

Abstract 4118380: In-Hospital Outcome of Acute Heart Failure in Patients with Active Chronic Lymphocytic Leukemia

Introduction: Chronic lymphocytic leukemia (CLL) is prevalent among adults in Western countries, posing a significant health challenge due to its incurable nature and associated complications. Among these, cardiovascular disease, particularly heart failure (HF), has emerged as a major concern. Despite growing recognition, understanding of acute HF's epidemiology, outcomes, and risk factors in CLL patients remains limited. To address these gaps, we conducted a large-scale study using the National Inpatient Sample (NIS) database, aiming to examine acute HF prevalence, trends, outcomes, and predictors among CLL hospitalizations. Methods: We employed a retrospective cohort design utilizing NIS data from 2016 to 2021. CLL hospitalizations with and without acute HF were identified using ICD-10 codes. Our analysis included demographic characteristics, in-hospital outcomes, and multivariable logistic regression to identify predictors of outcomes. Propensity score matching was performed to mitigate confounding factors. Results: Among 423,829 CLL hospitalizations, 27.8% presented with acute HF. Patients with acute HF were older and had higher rates of comorbidities. While acute HF prevalence remained stable, in-hospital mortality increased over time, contrasting with stable rates among patients without acute HF. Acute HF was associated with higher mortality, cardiogenic shock, cardiac arrest, and major adverse cardiovascular events. Propensity score-matched analysis confirmed these associations. Discussion: Our study highlights acute HF as a common complication in CLL hospitalizations, linked with worse outcomes. The multifactorial nature of HF in CLL involves disease-related factors, treatment toxicities, and traditional cardiovascular risk factors. Prompt recognition and multidisciplinary management are essential for improving outcomes. Future research should focus on developing risk stratification tools and interventions targeting acute HF in CLL patients. Conclusion: Acute HF poses a significant burden on CLL hospitalizations, emphasizing the need for heightened awareness and tailored management strategies. Our findings underscore the importance of early recognition and intervention to improve outcomes in this vulnerable population.

Considerations for Future Research and Methodological Clarifications on Smoking Behavior Change and Heart Failure Risk in Patients With Type 2 Diabetes.

Considerations for Future Research and Methodological Clarifications on Smoking Behavior Change and Heart Failure Risk in Patients With Type 2 Diabetes.

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 &gt;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 &gt;9, 59 (42%) a SYNTAX II score &gt;24 and 65 (47%) a Gensini score &gt;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 4124182: Depression Symptomatology as Predictor of Incident Major Vascular Outcomes: Results from the Hispanic Community Health Study/Study of Latinos

Background: Cardiovascular disease (CVD) has consistently been associated with higher depression symptoms and disorders. Conversely, fewer studies have shown that depression predicts risk of incident CVD and mortality. Objective: To examine the association of depression symptoms with incident major adverse cardiovascular events (MACE) among Hispanics/Latinos living in US. Methods: MACE-free Hispanic Community Health Study/Study of Latinos participants who underwent baseline evaluation between 2008-2011 (n=15,180) were included. MACE was defined as the composite of incident stroke, myocardial infarction (MI), or decompensated heart failure (HF), adjudicated using standard criteria up to year 2019. Depression symptoms were assessed at baseline with a 10-item Center for Epidemiological Studies Depression Scale (CES-D 10, range 0-30 points, 5 points increments), with clinically significant depression defined as CES-D 10 ≥10 points. The incident rate ratio (IRR) of MACE across CES-D 10 scores was determined using Poisson regression models, adjusting for baseline sociodemographic characteristics and Framingham Risk Scores. Analyses were weighted for complex survey design and non-response. Results: The mean age (95% CI) was 40.4 (39.9-40.9) years, and the mean CES-D 10 score was 8.4, 95%CI (7.2-9.5) for those with MACE vs 6.9, 95%CI (6.7-7.0) for individuals without MACE (p&lt;0.05). Clinically significant depression symptoms were present in 29% of the population. There were 321 total MACE outcomes that occurred between baseline and year 2019, with 120 MACE occurrences in individuals with CES-D 10 ≥10 points. In the fully adjusted model, increasing CES-D 10 was associated with higher incidence of MACE (for all: IRR 1.22, 95% CI (1.10-1.36); for those with CES-D 10 scores ≥10: IRR 1.62, 95% CI (1.21-2.17). Additionally, participants with CES-D 10 scores ≥10 were 1.4 times more likely to develop MACE compared to those with CES-D 10 scores &lt;10 (HR 1.41, 95% CI=1.13-1.83, Figure). Among MACE sub-components, incident HF was twice as high in the population with CES-D 10 ≥10 points versus those with CES-D 10 &lt;10 points (HR 2.36, 95% CI (1.58-3.51)). Conclusion: The findings of this cohort study indicate that depression symptomatology is associated with incident overall MACE and HF, and that clinically significant depression symptoms further increased risk for MACE and HF, making early treatment of depression a possible target for decreasing CVD incidence.

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.