Incident Heart Failure Hospitalization Research Articles

High Throughput Plasma Proteomics and Risk of Heart Failure and Frailty in Late Life

ImportanceHeart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions.ObjectiveTo identify shared pathways between incident HF and frailty in late life using large-scale proteomics.Design, Setting, and ParticipantsIn this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants in the Cardiovascular Health Study (CHS). Data analysis was conducted from February 2022 to June 2023.ExposuresProtein aptamers, measured at study V3 and V5.Main Outcomes and MeasuresOutcomes assessed included incident HF hospitalization after V3 and after V5, prevalent frailty at V5, and incident frailty between V5 and visit 6 (V6; 2016-2017; n = 4131). Frailty was assessed using the Fried criteria. Analyses were adjusted for age, gender, race, field center, hypertension, diabetes, smoking status, body mass index, estimated glomerular filtration rate, prevalent coronary heart disease, prevalent atrial fibrillation, and history of myocardial infarction. Mendelian randomization (MR) analysis was performed to assess potential causal effects of candidate proteins on HF and frailty.ResultsA total of 4877 protein aptamers were measured among 10 638 participants at V3 (mean [SD] age, 60 [6] years; 4886 [46%] men). Overall, 286 proteins were associated with incident HF after V3 (822 events; P < 1.0 × 10−5), 83 of which were also associated with incident after V5 (336 events; P < 1.7 × 10−4). Among HF-free participants at V5 (n = 3908; mean [SD] age, 75 [5] years; 1861 [42%] men), 48 of 83 HF-associated proteins were associated with prevalent frailty (223 cases; P < 6.0 × 10−4), 18 of which were also associated with incident frailty at V6 (152 cases; P < 1.0 × 10−3). These proteins enriched fibrosis and inflammation pathways and demonstrated stronger associations with incident HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. All 18 proteins were associated with both prevalent frailty and incident HF in CHS. MR identified potential causal effects of several proteins on frailty and HF.Conclusions and RelevanceIn this study, the proteins associated with risk of HF and frailty enrich for pathways related to inflammation and fibrosis as well as risk of HFpEF. Several of these proteins could potentially contribute to the shared pathophysiology of frailty and HF.

Invasive Hemodynamic Changes Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to lower incident heart failure (HF) and HF hospitalizations, but the mechanisms of benefit in relation to invasive hemodynamics remain unclear. Using PRISMA guidelines, we systematically reviewed multiple online databases for randomized trials evaluating the effect of SGLT2i on invasive hemodynamics. Rest and peak exercise invasive hemodynamics were measured via right heart catheterization pre- and postintervention. Random effects model meta-analysis at a 95% confidence interval was done using RevMan 5.0. A total of 3 studies with a total of 145 patients were included in the meta-analysis. SGLT2i was significantly associated with a reduction in pulmonary capillary wedge pressure at rest and peak exercise. Similarly, SGLT2i reduced mean pulmonary artery pressure at rest and peak exercise, respectively; however, this was not statistically significant. This hypothesis-generating study offers mechanistic insights into the central hemodynamic effects of SGLT2i underpinning the HF benefits of SGLT2i.

Transcatheter or Surgical Replacement for Failed Bioprosthetic Aortic Valves

The use of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) has been rapidly expanding as an alternative treatment to redo surgical aortic valve replacement (SAVR) for failed bioprosthetic valves despite limited long-term data. To assess mortality and morbidity in patients undergoing intervention for failed bioprosthetic SAVR. This was a retrospective population-based cohort analysis conducted between January 1, 2015, and December 31, 2020, with a median (IQR) follow-up time of 2.3 (1.1-4.0) years. A total of 1771 patients with a history of bioprosthetic SAVR who underwent ViV-TAVR or redo SAVR in California, New York, and New Jersey were included. Data were obtained from the California Department of Health Care Access and Information, the New York Statewide Planning and Research Cooperative System, and the New Jersey Discharge Data Collection System. Exclusion criteria included undergoing TAVR or redo SAVR within 5 years from initial SAVR, as well as infective endocarditis, concomitant surgical procedures, and out-of-state residency. Propensity matching yielded 375 patient pairs. Data were analyzed from January to December 2023. ViV-TAVR vs redo SAVR. The primary outcome was all-cause mortality. Secondary outcomes were stroke, heart failure hospitalization, reoperation, major bleeding, acute kidney failure, new pacemaker insertion, and infective endocarditis. From 2015 through 2020, the proportion of patients undergoing ViV-TAVR vs redo SAVR increased from 159 of 451 (35.3%) to 498 or 797 (62.5%). Of 1771 participants, 653 (36.9%) were female, and the mean (SD) age was 74.4 (11.3) years. Periprocedural mortality and stroke rates were similar between propensity-matched groups. The ViV-TAVR group had lower periprocedural rates of major bleeding (2.4% vs 5.1%; P = .05), acute kidney failure (1.3% vs 7.2%; P < .001), and new pacemaker implantations (3.5% vs 10.9%; P < .001). The 5-year all-cause mortality rate was 23.4% (95% CI, 15.7-34.1) in the ViV-TAVR group and 13.3% (95% CI, 9.2-18.9) in the redo SAVR group. In a landmark analysis, no difference in mortality was observed up to 2 years (hazard ratio, 1.03; 95% CI, 0.59-1.78), but after 2 years, ViV-TAVR was associated with higher mortality (hazard ratio, 2.97; 95% CI, 1.18-7.47) as well as with a higher incidence of heart failure hospitalization (hazard ratio, 3.81; 95% CI, 1.57-9.22). There were no differences in 5-year incidence of stroke, reoperation, major bleeding, or infective endocarditis. Compared with redo SAVR, ViV-TAVR was associated with a lower incidence of periprocedural complications and a similar incidence of all-cause mortality through 2 years' follow-up. However, ViV-TAVR was associated with higher rates of late mortality and heart failure hospitalization. These findings may be influenced by residual confounding and require adjudication in a randomized clinical trial.

Sex Differences in the Associations of Traditional Risk Factors and Incident Heart Failure Hospitalization: A Prospective Cohort Study of 102 278 Chinese General Adults.

Evidence regarding sex differences in the associations of traditional risk factors with incident heart failure (HF) hospitalization among Chinese general adults is insufficient. This study aimed to evaluate the potential sex differences in the associations of traditional risk factors with HF among Chinese general adults. Data were from a subcohort of the China PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project. The traditional risk factors were collected at baseline, and the study outcome was HF-related hospitalization identified from the Inpatients Registry. A total of 102 278 participants (mean age, 54.3 years; 39.5% men) without prevalent HF were recruited. A total of 1588 cases of HF-related hospitalization were captured after a median follow-up of 3.52 years. The incidence rates were significantly higher in men (2.1%) than in women (1.2%). However, the observed lower risk of HF in women was significantly attenuated or even vanished when several traditional risk factors were poorly controlled (P for sex-by-risk factors <0.05). The selected 11 risk factors collectively explained 62.5% (95% CI, 55.1-68.8) of population attributable fraction for HF in women, which is much higher than in men (population attributable fraction, 39.6% [95% CI, 28.5-48.9]). Although women had a lower incidence rate of hospitalization for HF than men in this study, the risk for HF increased more remarkably in women than in men when several traditional risk factors were poorly controlled. This study suggests that intensive preventative strategies are immediately needed in China.

Cardiovascular and mortality benefits of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists as third-step glucose-lowering medicine in patients with type 2 diabetes: a retrospective cohort analysis

IntroductionStudies have found that sodium-glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP1) have cardiovascular benefits for patients with type 2 diabetes (DM2) and atherosclerotic cardiovascular disease...

Risk Factors and Outcomes Associated With Heart Failure With Preserved and Reduced Ejection Fraction in People With Chronic Kidney Disease.

Heart failure (HF) is associated with poor outcomes in people with chronic kidney disease, yet it is unknown whether outcomes differ by HF subtype. This study aimed to examine associations of incident HF with preserved ejection fraction (HFpEF) versus HF with reduced ejection fraction (HFrEF) with progression to end-stage kidney disease (ESKD) and mortality. We studied individuals with chronic kidney disease in the CRIC study (Chronic Renal Insufficiency Cohort) who were free of HF at cohort entry. Incident HF hospitalizations were adjudicated and classified into HFpEF (ejection fraction, ≥50%) or HFrEF (ejection fraction, <50%) based on echocardiograms performed during the hospitalization or at a research study visit. ESKD was defined as need for chronic dialysis or kidney transplant. Cox proportional hazards were used to evaluate the association of time-updated HF subtype with risk of ESKD and mortality, adjusting for demographics, comorbidities, and medication use. Among the 3557 study participants without HF at cohort entry, mean age was 57 years and mean estimated glomerular filtration rate was 45 mL/min per 1.73 m2. A total of 682 participants had incident HF. Incidence rates for HFpEF and HFrEF were 0.9 (95% CI, 0.8-1.0) and 0.7 (95% CI, 0.6-0.8) per 100 person-years, respectively (Pdifference=0.005). Associations of incident HF with progression to ESKD were not statistically different for HFpEF (hazard ratio, 2.06 [95% CI, 1.66-2.56]) and HFrEF (hazard ratio, 1.80 [95% CI, 1.36-2.38]; P=0.42). The associations with mortality were stronger for HFrEF (hazard ratio, 2.73 [95% CI, 2.24-3.33]) compared with HFpEF (hazard ratio, 1.99 [95% CI, 1.65-2.40]; P=0.0002). In a chronic kidney disease population, the rates of HFpEF hospitalizations were greater than that of HFrEF. Risk of ESKD was high but not statically different across HF subtypes. There was a stronger association of HFrEF with mortality. Prevention and treatment of both HFpEF and HFrEF should be central priorities to improve outcomes in chronic kidney disease.

Abstract P166: Social Isolation and Social Support Are Associated With Self-Rated Health and Heart Failure Outcomes in the Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Social isolation (SI) and social support (SS) are associated with incidence of heart failure (HF). Few studies investigate how SI, SS, and subtypes of SS (appraisal, belonging, self-esteem, and tangible) measured before HF are related to morbidity and mortality after HF. Objective: Assess whether SI, SS, and subtypes of SS are associated with self-rated health trajectories and HF outcomes among participants with incident HF hospitalizations, and if results differ by sex or race. Methods: We included 2967 ARIC participants (51% female, 27% Black, mean age 59 (SD 6) years) with incident HF hospitalization after Visit 2 (1990-1992). We identified incident HF hospitalization as ICD-9 code 428 in any position and physician adjudicated events; on average HF occurred 17 (SD 8) years after Visit 2. We measured predefined SI categories and tertiles of SS at Visit 2 using the 10-item Lubben Social Network Scale and the 16-item Interpersonal Support Evaluation List, which were assessed as separate exposures. We assessed associations with trajectories of annually measured self-rated health in the 4 years prior to and after incident HF hospitalization, measured by the probability of being in excellent/good self-rated health (0-100% scale), using linear mixed effects models. We calculated hazard ratios (HR) and 95% confidence intervals (CIs) for associations with time to first all-cause rehospitalization and all-cause mortality using Cox proportional hazard models. Models were adjusted for age, sex, race-center, employment status, years of education, prior use of mental health medications, and time between Visit 2 and HF. Results: Over mean follow-up of 5 (SD 5) years after initial HF hospitalization, 90% of participants experienced rehospitalization and there were 2378 deaths. Low overall SS had a 5.8% (95% CI 7.8%, 3.8%) lower probability of excellent/good self-rated health over time than high SS; associations of subtypes of SS with this outcome were similar. Low belonging SS was associated with greater days to first rehospitalization (HR 0.85; 95% CI 0.79, 0.96) compared to the highest tertile, however belonging SS was not associated with mortality (HR 1.05; 95% CI 0.95, 1.17). Low tangible SS was associated with greater mortality among White (HR 1.14; 95% CI 1.01, 1.28) but not Black participants (HR 0.95; 95% CI 0.78, 1.16), compared to the highest tertile. Being socially isolated/high risk for SI was associated with greater hazard of all-cause mortality among females (HR 1.57; 95% CI 1.20, 2.06) but not males (HR 0.95; 95% CI 0.75, 1.19), compared to low SI. Conclusions: SI and SS measured before HF were relevant to HF outcomes, but relevance may vary by sex and race. In particular, greater SI was only associated with greater mortality among females, and lower tangible SS with greater mortality among White participants only. Belonging support was associated with some HF outcomes but not others.

Impact of Residential Social Deprivation on Prediction of Heart Failure in Patients With Type 2 Diabetes: External Validation and Recalibration of the WATCH-DM Score Using Real World Data.

Patients with type 2 diabetes are at risk of heart failure hospitalization. As social determinants of health are rarely included in risk models, we validated and recalibrated the WATCH-DM score in a diverse patient-group using their social deprivation index (SDI). We identified US Veterans with type 2 diabetes without heart failure that received outpatient care during 2010 at Veterans Affairs medical centers nationwide, linked them to their SDI using residential ZIP codes and grouped them as SDI <20%, 21% to 40%, 41% to 60%, 61% to 80%, and >80% (higher values represent increased deprivation). Accounting for all-cause mortality, we obtained the incidence for heart failure hospitalization at 5 years follow-up; overall and in each SDI group. We evaluated the WATCH-DM score using the C statistic, the Greenwood Nam D'Agostino test χ2 test and calibration plots and further recalibrated the WATCH-DM score for each SDI group using a statistical correction factor. In 1 065 691 studied patients (mean age 67 years, 25% Black and 6% Hispanic patients), the 5-year incidence of heart failure hospitalization was 5.39%. In SDI group 1 (least deprived) and 5 (most deprived), the 5-year heart failure hospitalization was 3.18% and 11%, respectively. The score C statistic was 0.62; WATCH-DM systematically overestimated heart failure risk in SDI groups 1 to 2 (expected/observed ratios, 1.38 and 1.36, respectively) and underestimated the heart failure risk in groups 4 to 5 (expected/observed ratios, 0.95 and 0.80, respectively). Graphical evaluation demonstrated that the recalibration of WATCH-DM using an SDI group-based correction factor improved predictive capabilities as supported by reduction in the χ2 test results (801-27 in SDI groups I; 623-23 in SDI group V). Including social determinants of health to recalibrate the WATCH-DM score improved risk prediction highlighting the importance of including social determinants in future clinical risk prediction models.

Neighborhood Disadvantage and Risk of Heart Failure: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Heart failure (HF) affects >6 million US adults, with recent increases in HF hospitalizations. We aimed to investigate the association between neighborhood disadvantage and incident HF events and potential differences by diabetes status. We included 23 645 participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), a prospective cohort of Black and White adults aged ≥45 years living in the continental United States (baseline 2005-2007). Neighborhood disadvantage was assessed using a Z score of 6 census tract variables (2000 US Census) and categorized as quartiles. Incident HF hospitalizations or HF-related deaths through 2017 were adjudicated. Multivariable-adjusted Cox regression was used to examine the association between neighborhood disadvantage and incident HF. Heterogeneity by diabetes was assessed using an interaction term. The mean age was 64.4 years, 39.5% were Black adults, 54.9% females, and 18.8% had diabetes. During a median follow-up of 10.7 years, there were 1125 incident HF events with an incidence rate of 3.3 (quartile 1), 4.7 (quartile 2), 5.2 (quartile 3), and 6.0 (quartile 4) per 1000 person-years. Compared to adults living in the most advantaged neighborhoods (quartile 1), those living in neighborhoods in quartiles 2, 3, and 4 (most disadvantaged) had 1.30 (95% CI, 1.06-1.60), 1.36 (95% CI, 1.11-1.66), and 1.45 (95% CI, 1.18-1.79) times greater hazard of incident HF even after accounting for known confounders. This association did not significantly differ by diabetes status (interaction P=0.59). For adults with diabetes, the adjusted incident HF hazards comparing those in quartile 4 versus quartile 1 was 1.34 (95% CI, 0.92-1.96), and it was 1.50 (95% CI, 1.16-1.94) for adults without diabetes. In this large contemporaneous prospective cohort, neighborhood disadvantage was associated with an increased risk of incident HF events. This increase in HF risk did not differ by diabetes status. Addressing social, economic, and structural factors at the neighborhood level may impact HF prevention.

Clinical utility of QRS duration normalized to left ventricular volume for predicting cardiac resynchronization therapy efficacy in patients with “mid-range” QRS duration

BackgroundCardiac resynchronization therapy (CRT) is effective for patients with heart failure with QRS duration (QRSd) ≥150 ms. However, its beneficial effect seems to be limited for those with “mid-range” QRSd (120–149 ms). Recent studies have demonstrated that modifying QRSd to left ventricular end-diastolic volume (LVEDV)—modified QRSd—improves the prediction of clinical outcomes of CRT. ObjectiveThe purpose of this study was to investigate the clinical impact of the modified QRSd on the efficacy of CRT in patients with “mid-range” QRSd. MethodsWe conducted a retrospective, multicenter, observational study, with heart failure hospitalization (HFH) after CRT as the primary endpoint. Modified QRSd is defined as QRSd divided by LVEDV, determined through the Teichholtz method of echocardiography. ResultsAmong the 506 consecutive patients considered, 119 (mean age 61 ± 15 years; 80% male, QRSd 135 ± 9 ms) with a “mid-range” QRSd who underwent de novo CRT device implantation were included for analysis. During median follow-up of 878 days [interquartile range 381–1663 days], HFH occurred in 45 patients (37%). Fine-Gray analysis revealed modified QRSd was an independent predictor of HFH (hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.96–0.99; P <.01). Receiver operating characteristic curve analysis revealed a cutoff value of 0.65 ms/mL for the modified QRSd in predicting HFH. Patients above the threshold exhibited a significantly lower incidence of HFH than patients below the threshold (HR 0.46; 95% CI 0.25–0.86; P = .01). ConclusionModified QRSd can effectively predict the efficacy of CRT in patients with a “mid-range” QRSd.

Outcomes of left bundle branch area pacing compared to His bundle pacing and right ventricular apical pacing in Japanese patients with bradycardia.

His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) emerge as better alternatives to right ventricular apical pacing (RVAP) in patients with bradycardia requiring permanent cardiac pacing. We aimed to compare the clinical outcomes of LBBAP, HBP, and RVAP in Japanese patients with bradycardia. A total of 424 patients who underwent successful pacemaker implantation (HBP, n = 53; LBBAP, n = 75; and RVAP, n = 296) were retrospectively enrolled in this study. The primary study endpoint was the cumulative incidence of heart failure hospitalization (HFH) during the follow-up. The success rate for implantation was higher in the LBBAP group than in the HBP group (94.9% and 81.5%, respectively). Capture threshold increase >1V during the follow-up occurred in the HBP and RVAP groups (9.4% and 5.1%, respectively), while it did not in the LBBAP group. The cumulative incidence of HFH was significantly lower in the LBBAP group than the RVAP (adjusted hazard ratio, 0.12 [95% confidence interval: 0.02-0.86]; p = .034); it did not differ between the HBP and RVAP groups (adjusted hazard ratio, 0.48 [95% confidence interval: 0.17-1.34]; p = .16). Advanced age, mean percent right ventricular pacing (per 10% increase), left ventricular ejection fraction <50%, and RVAP were associated with HFH. Compared to RVAP and HBP, LBBAP appeared more feasible and effective in patients with bradycardia requiring permanent cardiac pacing.

Descriptions of Etiology, Clinical Course, and Prognosis of Patients Presenting with Pericardial Effusion.

Pericardial effusion (PE) presentation varies from an incidental finding to a life-threatening situation; thus, its etiology and clinical course remain unknown. The aim of the present study was to retrospectively investigate these factors.We analyzed 171 patients (0.4%) who presented with PE among 34,873 patients who underwent echocardiography between 2011 and 2021 at our hospital. Clinical and prognostic information was retrieved from electronic medical records. The primary endpoints were all-cause death, hospitalization due to heart failure (HF), and other cardiovascular events such as cardiovascular death, acute coronary syndrome, elective percutaneous coronary intervention, and stroke.The etiologies of PE were as follows: idiopathic (32%), HF-related (18%), iatrogenic (11%), cardiac surgery-related (10%), radiation therapy-related (9%), malignancy (8%), pericarditis/myocarditis (8%), myocardial infarction-related (2%), and acute aortic dissection (2%). Patients with idiopathic/HF etiology were more likely to be older than the others.During a mean follow-up period of 2.5 years, all-cause death occurred in 21 patients (12.3%), cardiovascular events in 10 patients (5.8%), and hospitalization for HF in 24 patients (14.0%). All-cause death was frequently observed in patients with malignancy (44% per person-year). Cardiovascular events were mostly observed in patients with radiation therapy-related and malignancy (8.6% and 7.3% per person-year, respectively).The annual incidence of hospitalization for HF was the highest in patients with HF-related (25.1% per person-year), followed by radiation therapy-related (10.4% per person-year).This retrospective study is the first, to the best of our knowledge, to reveal the contemporary prevalence of PE, its cause, and outcome in patients who visited a cardiovascular hospital in an urban area of Japan.

Prognostic value of growth differentiation factor-15 3 months after an acute chest pain admission

ObjectiveGrowth differentiation factor-15 (GDF-15) is a predictor of death and cardiovascular events when measured during index hospitalisation in patients with acute chest pain. This study investigated the prognostic utility of...

The effect of SGLT2 inhibitor on clinical outcomes in patients with type 2 diabetes and atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia and represents a significant public health burden with an increased risk of stroke, heart failure (HF) and mortality. Sodium glucose cotransporter 2 (SGLT2) inhibitors improve clinical outcomes in several populations including type 2 diabetes, chronic renal insufficiency, and HF. However, limited data exist on their effects on AF. Purpose We investigated impact of SGLT2 inhibitor on clinical outcomes compared to dipeptidyl peptidase 4 (DPP4) inhibitor among patients with type 2 diabetes and AF. Methods We conducted a retrospective cohort study using the National Health Insurance Service database. A total of 4,771 patients with type 2 diabetes and AF who were newly prescribed SGLT2 inhibitors or DPP4 inhibitors from Jan 2014 to Dec 2019 were selected and matched in a 1:2 ratio by propensity score with 38 confounding variables. We assessed the relationship of SGLT2 inhibitor with clinical outcomes including mortality, stroke, myocardial infarction (MI) and hospitalization for HF compared with DPP4 inhibitor using Cox regression model. Results Over the follow-up, 181 patients (3.7%) died, 121 patients (2.5%) were hospitalized for HF, 95 patients (2.0%) experienced MI, and 293 patients (6.1%) had stroke. Compared to DPP4 inhibitor, SGLT2 inhibitor was associated with lower risk of mortality (HR 0.61; 95% CI 0.39-0.94; P=0.025), but not of MI (HR 1.22 [95% CI 0.71-2.08]; P=0.46) or stroke (HR 1.0 [95% CI 0.75-1.33]; P=0.98). While the incidence of hospitalizations for HF tended to be lower in the SGLT2 inhibitor group, it did not reach a statistical significant level (HR 0.63 [95% CI 0.39-1.02]; P=0.06). Conclusion In a nationwide cohort of patients with type 2 diabetes and AF, SGLT2 inhibitor was associated with a lower risk of mortality compared to DPP4 inhibitor.

External validation of the new REACT-HF score for heart failure prediction in patients with atrial fibrillation

Abstract Background Heart failure (HF) represents the main cause of hospital admissions and deaths among atrial fibrillation (AF) patients, but precise risk prediction tools are lacking. Recently, the REACT-HF score has been developed to predict incident HF hospitalizations or cardiovascular (CV) death within 2-years based on 12 variables (sex, age, height, creatinine clearance, diabetes, vascular disease, valvular heart disease, heart rate and rhythm, left ventricular hypertrophy and intraventricular conduction delay). Purpose The aim of the present study was to externally validate the REACT-HF score within the Swiss-AF and BEAT-AF cohorts, and to investigate whether this score model can be improved by adding biomarkers (hs-CRP, NT-proBNP, hs-TNT). Methods We included 2’599 AF patients from the Swiss- and BEAT-AF cohorts without prior history of HF, with at least one follow-up and with all baseline variables needed for the REACT-HF score. To validate the score, we estimated a Cox model with the original score as the only predictor. We further explored whether the predictive performance of the REACT-HF score model could be improved by adding any combination of the above listed biomarkers. The primary outcome was incident HF hospitalization or CV death. Secondary outcomes included the individual components of the primary outcome and all-cause mortality. Results Mean age was 70.2 years, 29.1% were female and 54.8% had paroxysmal AF. The mean CHA2DS2-VASc score was 2.7 (+/- 1.6). The most frequent comorbidities were hypertension (65%), diabetes (12%), vascular disease (23%) and coronary artery disease (36%). Most patients (1’883) presented a very low REACT-HF score below 0.05 (72.4%), 530 patients between 0.05 and below 0.1 (20.4%) and 186 had a risk score of 0.1 and above (7.2%). In the validation set, 380 (14.6%), 471 (18.1%), 511 (19.7%) 561 (21.6%) and 676 (26.0%) patients were categorized in the lowest to the highest quintiles based on the original score`s quintiles. Figure 1 shows the Kaplan-Meier survival curves for the primary endpoint of first HF hospitalization or CV death by quintiles of the REACT-HF score, applied in our pooled cohort. And Figure 2 shows the Kaplan-Meier curves for the 1st HF hospitalization. The incidence rates at 2-year follow-up per 100 patient-years of the primary outcome (0.39, 0.59, 1.58, 3.97, 7.53), HF hospitalization (0.39, 0.49, 1.38, 2.75, 6.26), CV death (0.0, 0.10, 0.20, 1.29, 2.12), and all cause-death (0.10, 0.49, 0.78, 2.29, 4.24) all increased gradually among the quintiles of risk score. The estimated c-statistic for the composite primary outcome was 0.764 (approximate 95% CI, 0.723-0.806). The best biomarker enhanced-model within our cohort was the model including hs-CRP and NT-proBNP (c-statistic 0.810). Conclusions The REACT-HF score discriminates well for prediction of HF hospitalization and CV death in a contemporary AF population and can be improved by including NT-pro-BNP and hs-CRP.

Abstract 13834: Prognosis of Patients With Atrial Fibrillation and Weight Loss: The Fushimi AF Registry

Background: Atrial fibrillation (AF) is a common cardiac arrythmia in the elderly, in whom frailty is often a clinical issue. Weight loss is one of the key factors of frailty, and we previously reported that low body wight (≤50 kg) was associated with higher mortality and morbidity in patients with AF. However, the association of weight loss with prognosis of AF patients is unclear. Methods: The Fushimi AF registry is a community based prospective survey of AF patients in Japan. We collected data on body weight annually, and changes in body weight were obtained in 2,922 patients (mean age, 73 years; female 39.3%; mean body weight 59.8 kg). We defined weight loss as decrease in body weight ≥ 4.5 kg or 5% in the past year based on the frailty-defining criteria in the Cardiovascular Health Study. Results: During the follow-up, 1319 patients had weight loss (7.9% per person-year). Patients with weight loss were older, and had more hypertension, diabetes, coronary artery disease, chronic kidney disease, and heart failure at baseline than those without. Prevalence of prior stroke/systemic embolisms (SE) and major bleeding were similar between patients with and without weight loss. In the logistic regression analysis, hypertension, diabetes, chronic kidney disease, and heart failure were positively associated with development of weight loss, and incidence of stroke/SE was inversely associated with weight loss. Landmark analysis after the onset of weight loss revealed that patients with weight loss showed significantly higher incidence of all-cause death and cardiac death. Incidence of heart failure hospitalization, stroke/SE, and major bleeding were comparable between patients with and without weight loss. After adjustment for clinical confounders, weight loss was significantly associated with the incidence of all-cause death (hazard ratio, 1.79; 95% confidence interval, 1.54-2.09) and cardiac death (hazard ratio, 1.67; 95% confidence interval, 1.15-2.43). Subgroup analyses revealed that weight loss was also significantly associated with higher all-cause and cardiac mortality regardless of age, sex, and body weight at baseline. Conclusion: In AF patients, weight loss was significantly associated with higher all-cause and cardiac mortality.

Abstract 11978: Invasive Hemodynamic Changes Associated With Sodium Glucose Transporter-2 Inhibitors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Sodium-Glucose cotransporter-2 inhibitors (SGLT2i) have been shown to lower incident heart failure (HF) and HF hospitalizations, but the mechanism of benefits in relation to invasive hemodynamics remain unclear. This meta-analysis explores the central hemodynamic effects of SGLT2i. Methods: Using PRISMA guidelines, we systematically reviewed PubMed, Embase, CINAHL, Cochrane library, Ovid MEDLINE, and Google scholar from inception to April 2023 for randomized trials evaluating the effect of SGLT2i on central hemodynamics. Included patients were on guideline directed medical therapy and SGLT2i was added in the experimental group compared to placebo for 3-6 months. Rest and peak-exercise central hemodynamics was measured via right heart catheterization pre- and post-intervention. Random-effect model meta-analysis at 95% confidence interval (CI) was done using RevMan 5.4. Results: Out of 267 articles identified, 3 studies with a total of 145 patients were included in the meta-analysis. The mean age was 62.8 + 4.0 years, 70.0% were male and mean BMI was 31.9 + 2.2. Compared to placebo, SGLT2i were associated with reduction in weighted mean difference of pulmonary capillary wedge pressure (PCWP) by 2.71 (95% CI: -4.33 to -1.08, I 2 =2%, p = 0.001) and 4.17 (95% CI: -7.20 to -1.13, I 2 =0%, p = 0.007) mmHg at rest and peak exercise respectively. Similarly, SGLT2i reduced mean pulmonary artery pressure (mPAP) by 1.16 (95% CI: -3.00 to 0.69, I 2 =0%, p = 0.22) and 2.73 (95% CI: -5.63 to 0.18, I 2 =20%, p = 0.07) mmHg at rest and peak exercise respectively, however this was not statistically significant. Conclusions: SGLT2i significantly reduced PCWP at rest and peak exercise. Rest and peak exercise mPAP were also reduced compared to baseline but not statistically significant. This hypothesis-generating study offers mechanistic insights into the association of favorable hemodynamic effects underpinning to the HF benefits of SGLT2i.

Abstract 17631: Diabetic Retinopathy and Risk of Heart Failure Subtypes: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Although diabetic retinopathy is associated with higher risk of incident heart failure (HF), its associations with HF subtypes (HF with preserved ejection fraction [HFpEF] and HF with reduced ejection fraction [HFrEF]) largely remain unknown. Hypothesis: Diabetic retinopathy, a microvascular complication of hyperglycemic states, is more strongly associated with HFpEF than with HFrEF. Methods: We included 5038 ARIC participants who underwent fundus photography at Visit 3 (1993-1995), had diabetes or prediabetes, and were free of HF (mean age 60 years, 48% women, 27% Black adults). Retinopathy was graded according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) grading scale, with a severity score ≥14 defining the presence of any retinopathy. We used data on incident HF hospitalization. Information on HF subtypes was only available from 2005 onwards. We used Cox regression to estimate the associations of retinopathy with incident overall HF. For HF subtypes, to account for the competing risks of HFpEF and HFrEF, we used competing risks regression analysis by the proportional sub-hazards Fine and Gray method. Results: Over a median 21.2 years of follow-up, there were 1358 HF events (461 prior to 2005 and 897 post-2005 [including 418 HFpEF and 383 HFrEF]). The presence of diabetic retinopathy conferred higher risk of overall HF (hazard ratio [HR]: 1.84, 95% confidence interval [CI]: 1.55, 2.20). Among participants with information on HF subtypes post-2005 (n= 4120), diabetic retinopathy significantly increased the risk of HFpEF (HR 1.86, 95% CI: 1.28, 2.71), but not of HFrEF (sub-HR: 0.73, 95% CI: 0.45, 1.20). An increasing severity of diabetes retinopathy was associated with increasing risks of overall HF and HFpEF. Conclusions: The presence of diabetic retinopathy signifies an excess risk of HF, primarily HFpEF. Our findings support a strong contribution of microvascular disease to the development of HFpEF.

Abstract 18179: Metabolic Biomarker Signatures for Incident Heart Failure Hospitalisation Compared to Different Types of Cardiovascular Events: Evidence From NMR Metabolomics in 250,000 Individuals

Introduction: Metabolomic biomarker profiling by Nuclear Magnetic Resonance (NMR) is a powerful technique to examine molecular signatures for heart failure risk and clarify pathological differences to cardiovascular outcomes. Hypothesis: Blood lipids and metabolite biomarkers may differ in how they relate to prediction of heart failure vs coronary and stroke outcomes. Methods: We measured detailed plasma lipids and metabolites by NMR metabolomics in ~250,000 individuals from UK Biobank. We assessed shared and discordant biomarkers for heart failure hospitalisation in relation to myocardial infarction, ischemic stroke, peripheral artery disease, cardiac arrest and cardiovascular death. During 10 years of follow-up, 7.800 incident heart failure hospitalisation events occurred and 5-10.000 incident events for cardiovascular outcomes. Results: The overall pattern of biomarker associations differed for heart failure compared to for example, myocardial infarction, with biomarkers of LDL metabolism and apolipoprotein being especially discordant (Figure). In contrast, biomarkers of chronic inflammation and circulating fatty acids were concordant for the risk of heart failure and myocardial infarction. There were also prominent differences in the metabolic biomarker signatures for the risk of different types of cardiovascular diseases, such as between chronic ischemic heart disease, and different types of stroke. The biomarker association magnitudes were strongest for cardiovascular mortality and especially strong for short time to event onset. Conclusions: Heart failure and different cardiovascular endpoints have partly different metabolic biomarkers signatures. These may represent pathophysiological differences and have relevance for cardiovascular risk prediction, especially if using the five-point major adverse cardiovascular event definition.

Abstract 14300: Biomarkers of Myocardial Injury, but Not Systemic Inflammation, Predict the Risk of Incident Ventricular Arrhythmia

Background: Cardiac troponins and biomarkers of inflammation are elevated in heart failure (HF) and predict cardiovascular risk. Whether these biomarkers associate with risk of ventricular arrhythmias (VA) is unclear. Purpose: To assess whether cardiac Troponin T (cTnT), growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations are associated with incident VA. Methods: In a prospective, observational study of patients treated with implantable cardioverter defibrillator (ICD), cTnT, GDF-15, IL-6, and CRP were measured at baseline and after 1.4±0.5y, and associated with ICD-detected incident VA, HF hospitalizations and mortality. Results: We included 489 patients, aged 66±12y and 83% were men. Median (quartile 1-3) concentrations of cTnT were 15 (9-25) ng/L at inclusion, and higher concentrations were associated with higher age, male sex, diabetes mellitus, coronary artery disease (CAD), and HF. During 3.1±0.7y follow-up, 137 (28%) patients had ≥1 VA. cTnT concentrations were associated with an increased VA risk (HR 1.63 [95% CI 1.31-2.01] per log-unit, p&lt;0.001), also after adjustment for age, sex, BMI, CAD, HF, renal function, and LVEF (p&lt;0.001). GDF-15, IL-6, and CRP concentrations were not associated with incident VA, but all (including cTnT) were associated with HF hospitalization and mortality. Changes in cTnT, GDF-15, IL-6, and CRP from baseline to 1.4y were not associated with subsequent VA. Conclusions: Higher concentrations of cTnT, GDF-15, IL-6, and CRP associate with HF hospitalization and death, but only cTnT predicts incident VA. These findings suggest that myocardial injury rather than inflammation may play a pathophysiological role in VA and sudden cardiac death.