Incidence Of Heart Failure Research Articles

Incident heart failure: comparing management and outcome in primary and hospital settings in Western Sweden 2008-2017.

Heart failure (HF) is a highly prevalent condition managed in both primary care (PC) and hospital care (HC)-based settings. HF patients managed in these two settings may differ in their demography, comorbidities and outcomes, so we aimed to compare the patient management in PC and HC in the Västra Götaland Region (VGR) in Sweden. The VEGA database is an administrative database that includes all patients living in VGR. Patients with a first principal or contributory diagnosis of HF (I50) ≥18years old between 2008 and 2017 were included. One-year mortality was used as the outcome. In total, 35375 new-onset HF cases were included with 18722 identified only in PC and 16651 in HC. HF patients in PC were older (80.7±10.9 vs. 76.1±13.6), more women (57.1% vs. 44.9%), with more hypertension, musculoskeletal and mental disorders, but less myocardial infarction. Patients in HC had almost 4 times higher all-cause 1year mortality [3.92 (3.77-4.08), P<0.0001] compared with PC after adjustment for age and sex. Over a 10year period, despite decreasing mortality in both settings, hazard ratios for HC versus PC were significantly increased for all patients (P for interaction 0.0004), which was more marked in female and for 70-80years old patients. Over a 10year period, we demonstrated the differences in demography, comorbidities and outcomes between heart failure patients managed in hospital care versus primary care.

The Association of Hospital-Cardiologist Integration With Patient Outcomes, CareQuality, and Utilization.

Cardiologists are increasingly moving from independent practice to direct employment by hospitals. Hospital employment has the potential to improve care coordination and delivery, but little is known about its effect on care quality and outcomes. In this study, we sought to assess the association between hospital employment of cardiologists and patient outcomes, care quality, and utilization among patients hospitalized with incident acute myocardial infarction (AMI) or heart failure (HF). We used a sample of Medicare fee-for-service beneficiaries hospitalized with incident AMI or HF from 2008 to 2019. We identified the accountable cardiologists that cared for these patients and determined their employment status by means of tax identification numbers. We used difference-in-differences methods to compare clinical outcomes, quality measures, and utilization for patients treated by hospital-employed cardiologists after switching from independent to hospital-employed practice, to outcomes for patients treated by cardiologists who remained independent. Models were adjusted for time trends and patient, hospital, and cardiologist characteristics. Patient outcomes were in-hospital mortality, 30-day mortality, and 30-day readmission. Quality measures were receipt of: 1) a guideline-recommended test to assess cardiac function; and 2) a 30-day follow-up clinic visit. Utilization measures were length of stay and, for AMI patients, the proportion receiving coronary revascularization. The proportion of U.S. cardiologists employed by hospitals increased from 26% in 2008 to 63% in 2019. We identified 186,052 AMI and 259,849 HF patients cared for by cardiologists who switched to hospital employment and 168,052 AMI and 245,769 HF patients cared for by independent cardiologists. Patient characteristics were similar (mean age 80.8 years; 47% men). We found no significant differences in outcomes (eg, adjusted difference in 30-day mortality 0.03% [95%CI:-0.39% to 0.45%] for AMI patients and-0.05% [95%CI:-0.37% to 0.27%] for HF patients); no differences in most quality metrics except a small increase in the proportion of HF patients with 30-day follow-up (adjusted difference: 1.04%; 95%CI: 0.46%-1.62%); and no differences in utilization between patients treated by hospital-employed cardiologists (postswitch) vs independent cardiologists. Among U.S. cardiologists, there has been a large shift from independent practice to direct employment by hospitals. We found minimal evidence that cardiologist employment by hospitals improves care quality or outcomes.

Abstract 4145802: Association between Glucagon-like peptide-1 receptor agonists and risk of Arrhythmias or Heart Failure among patients with Type 2 Diabetes: A Meta-Analysis of 29 Randomized Controlled Trials.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a reduction in major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). However, their effect on reducing the risk of incidence of arrhythmias and heart failure has not been established, and there is very limited literature to date. Objective: We evaluated the effect of GLP-1 RAs on the incidence of arrhythmias and heart failure among patients with T2DM. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that enrolled patients with type 2 diabetes and compared GLP-1 RAs and control groups. PubMed and ClinicalTrials.gov were systematically searched from inspection till May 2024 without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model. Results: A total of 29 RCTs with 72,868 patients (35,631 in the GLP-1 RA group and 37,237 in the control group) were included in the analysis. Pooled analysis showed that there is no significant association between GLP-1 RAs and incidence of atrial fibrillation (OR, 0.94(95%CI: 0.75-1.18), P=0.60), atrial flutter (OR, 0.87(95%CI: 0.60-1.26), P=0.46), cardiac arrest (OR, 0.79(95%CI: 0.51-1.23), P=0.30), ventricular tachycardia (OR, 1.37(95%CI: 0.90-2.07), P=0.14), and ventricular fibrillation (OR, 0.91 (95%CI: 0.45-1.84), P=0.80) when compared with control group. However, GLP-RAs reduced the incidence of atrioventricular block complete (OR, 0.58 (95%CI: 0.35-0.97), P=0.04), and heart failure (OR, 0.795 (95%CI: 0.634-0.997), P=0.047). Conclusion: This study shows that GLP-1 RAs reduced the incidence of atrioventricular block complete and incidence of heart failure. However, no significant association has been observed for arrhythmias.

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 4126000: The Association of Cardiologist Vertical Integration With Care Quality, Patient Outcomes, and Utilization

Introduction: U.S. healthcare has experienced substantial growth in vertical integration (physicians employed by hospitals), but little is known about its effect on patient care. Aims: To assess the association between cardiologist vertical integration and patient outcomes, care quality, and utilization among patients hospitalized with incident acute myocardial infarction (AMI) or heart failure (HF). Methods: We used a sample of all Medicare fee-for-service beneficiaries hospitalized with incident AMI and a 75% sample of beneficiaries hospitalized with incident HF between 2008-2019. We identified the accountable cardiologists that cared for these patients and determined their integration status using tax identification numbers. We used difference-in-differences methods to compare outcomes for patients treated by integrated cardiologists after switching from non-integrated to integrated practice, to outcomes for patients treated by cardiologists who remained non-integrated. Patient outcomes were in-hospital mortality, 30-day mortality, and 30-day readmission. Quality measures were the proportion of patients that received 1) a guideline-recommended test to assess cardiac function and 2) a 30-day follow-up clinic visit. Utilization measures were length of stay and the proportion of AMI patients receiving percutaneous coronary intervention. Models were adjusted for time trends and patient, hospital, and cardiologist characteristics. Results: The proportion of U.S. cardiologists employed by hospitals increased from 26% in 2008 to 61% in 2018. We identified 186,052 AMI patients and 259,849 HF patients cared for cardiologists who switched to integrated practice and 168,052 AMI patients and 245,769 HF patients cared for by non-integrated cardiologists. Patients were similar in age, sex, race/ethnicity, and comorbidities. We found no significant differences in clinical outcomes (e.g., adjusted difference in 30-day mortality 0.03% [95% CI = -0.39%, 0.45%] for AMI and -0.05% [-0.37%, 0.27%] for HF patients); no differences in most quality metrics, and no differences in utilization between patients treated by integrated versus non-integrated cardiologists. Conclusions: We found minimal evidence that cardiologist employment by hospitals improves care quality or outcomes. Regulation of vertical integration should focus on other effects of integration such as higher prices paid by insurers.

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 4127345: National Cohort Study on Hypertensive Disorders of Pregnancy Among Women with Congenital Heart Disease: Insights from Multiple Centers

Background: Hypertensive disorders of pregnancy (HDP) are among the primary reasons for maternal and perinatal deaths globally. Encompassing chronic hypertension, pregnancy induced hypertension (PIH), and preeclampsia, HDP are among the most frequent complications encountered during pregnancy. Considering the emerging congenital heart disease (CHD) population globally, research on HDP in pregnancies with CHD is urgently needed. Methods: Outcomes for 2220 pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. Maternal death, cardiac complications, obstetric and offspring complications of completed pregnancies and their demographics, cardiac characteristics, and comorbidities were collected. To identify the risk factors for HDP, univariate and multivariate analysis were performed through logistic regression. Results: Of 2220 completed pregnancies with CHD from 7 tertiary institutions, 77 women had PIH, and 76 women had preeclampsia. The main CHD diagnosis of patients with PIH was shunt lesion (including ASD, VSD, and PDA), left heart abnormality (including AS/AI, BAV, and COA), and single ventricle (SV). The main CHD diagnosis of patients with preeclampsia was shunt lesion (including ASD, VSD, and PDA), left heart abnormality (including AS/AI and MS/MI), and right heart abnormality (including TOF, PS/PAS/PI, DORV and DCRV). In parturients with PIH, the mortality and incidence of heart failure were 2.60% and 15.58%, respectively. In parturients with preeclampsia, the mortality and incidence of heart failure were 6.58% and 23.68%, respectively. Pregnancies with HDP had a significantly higher incidence of adverse maternal and offspring events than pregnancies without HDP. Independent risk factors for HDP included multiple gestation, use of medically assisted reproduction, having elevated brain natriuretic peptide (BNP) level, delayed first ANC visit, and absence of strict antenatal supervision. Conclusion: In summary, the presence of HDP in women with CHD significantly increased the risk of mortality and morbidity for both the mother and the child, particularly in cases involving preeclampsia.

Abstract 4136285: Large-Scale Proteomics Identifies Novel Shared Biomarkers of Heart Failure and Cancer: the Atherosclerosis Risk in Communities (ARIC) Study

Introduction: There is a bidirectional relationship between cancer and cardiovascular disease risk. Identifying proteins associated with both cancer and heart failure (HF) may provide insight into common biological pathways underlying both conditions. Methods: Among 10,136 participants in the community-based ARIC cohort study who were free of HF and cancer at study visit 2 (1990-92) and had aptamer-based proteomics (SomaScan v4), we assessed the association of 4,955 plasma proteins with incident HF and with incident site-specific cancer ascertained by cancer registry linkage supplemented with medical records (lung, post-menopausal breast, prostate, colorectal, and hematologic) using multivariable Cox models adjusted for demographics, clinical characteristics, and social determinants of health. Two-sample cis-Mendelian randomization ( cis- MR) was performed to evaluate potential causal effects of proteins on HF, left ventricular (LV) function, and site-specific cancer. Results: Mean age at baseline was 56±6; 54% were female; and 24% reported black race. Over a median follow-up of 10 [IQR 10, 10] years, there were 604 incident HF events and 1,207 incident cancers (169 lung, 85 hematologic, 105 colorectal, 206 breast, 288 prostate). Using a Bonferroni significance threshold (p &lt; 1.0x10 -5 ), 23 proteins were associated with both HF and lung cancer, 2 with HF and hematologic malignancy, 1 with HF and colorectal cancer, and none with HF and breast or prostate cancer. Six proteins remained significantly associated with both HF and lung cancer after further adjustment for pack-years of smoking (Figure). In cis- MR of these six proteins, ICAM5 and MMP12 showed potential causal effect on LV volume and lung adenocarcinoma, and PLAUR showed potential causal effect on HF and lung adenocarcinoma. Conclusion: Among various types of cancer, proteins associated with lung cancer showed the greatest overlap with proteins associated with HF, which was largely accounted for by smoking exposure. We uncovered a set of 6 plasma proteins associated with both incident HF and lung cancer after accounting for smoking. MR identified proteins with potential causal effects on both lung adenocarcinoma and LV size (ICAM5, MMP12) and HF (PLAUR).

Abstract 4135281: Bidirectional Associations of Chronic Kidney Disease and Heart Failure are Frequent and Associated with Higher Mortality: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Chronic kidney disease (CKD) and heart failure (HF) are interrelated but the bidirectional associations between the two conditions are not completely understood. Hypothesis: Bidirectional associations between CKD and HF are common in ambulatory populations and have implications for survival. Methods: We conducted a prospective cohort study of 11595 participants who attended ARIC Visit 4 (1996-98) with data on prevalent CKD and HF status, with follow-up for incident events through 2021. We assessed the prospective association of prevalent CKD (defined as eGFR&lt;60 ml/min per 1.73 m 2 or urine albumin-creatinine ratio of ≥30 mg/g) at Visit 4 with incident HF. We also assessed the association of prevalent HF at Visit 4 with incident CKD through 2019. Analyses accounted for mortality as a competing risk. We cross-categorized CKD and HF at Visit 4 and assessed prospective associations with mortality relative to those with neither condition. Results: The mean age in the study population was 63 years, with 56% women; and 23% Black adults. Among 1222 with prevalent CKD, 529 (43%) developed HF; among 433 with prevalent HF, 137 (31%) developed CKD. After multivariable adjustment, prevalent CKD (vs no CKD) was associated with incident HF (HR 1.87; 95% CI, 1.65–2.12; Figure ). Prevalent HF (vs no HF) was also associated with incident CKD (HR 1.33; 95% CI, 1.09–1.62). The co-occurrence of prevalent CKD and HF was associated with greater mortality risk (HR, 2.07; 95% CI, 1.78–2.42) than prevalent CKD alone (HR, 1.47; 95% CI, 1.37–1.59) or prevalent HF alone (HR, 1.33; 95% CI, 1.18–1.50), when compared with neither condition ( p interaction &lt;0.001). Conclusions: Bidirectional associations between CKD and HF are common in ambulatory populations. The co-existence of both CKD and HF is associated with higher mortality compared to either alone. There is a need to refine strategies to mitigate risk associated with bidirectional CKD and HF associations.

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 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 4147617: Depression and the Development of Cardiovascular Disease: Insights from All of Us Research Program

Introduction/Background: Depression is recognized as a risk factor for worse outcomes in patients with cardiovascular disease, but there is limited research on whether individuals with depression have an increased incidence of future cardiovascular disease. Research questions/Hypothesis: Do individuals with depression have an increased incidence of cardiovascular disease? Goals/Aims: This study was conducted to evaluate the association between a diagnosis of depression and the risk of developing future cardiovascular events, to determine whether the treatment of depression should be considered as a primary form of cardiovascular disease prevention. Methods/Approach: We conducted a prospective analysis using the “All Of Us” Research Program dataset. Participants who responded to the historical depression status in the “Personal/Family History Survey” and with linked electronic health records data were considered eligible for this study. We used Cox regression models to calculate the incidence of myocardial infarction (MI), stroke, heart failure (HF), and atrial fibrillation (AF) and the hazard ratio (HR) of a diagnosis of depression. Models were adjusted for sex, race, age, and prevalent hypertension, diabetes mellitus, hyperlipidemia, and smoking. The survival analysis of the four outcomes was conducted in parallel. We conducted sensitivity analysis by excluding participants with documentation of prior MI, stroke, HF, and/or AF. Results/Data: 100,030 participants were included in this study, with a mean age of 53.2 (standard deviation of 16.5). 68.4% of participants were female, 10% were Hispanic, 9.6% were Black, and 37.1% had a diagnosis of depression. The median follow up time was 3 years. Compared to participants without depression, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.05–1.41), stroke (aHR 1.68, 95% CI 1.06–2.68), HF (aHR 1.28, 95% CI 1.15–1.43), and AF (aHR 1.14, 95% CI 1.02–1.27). In the sensitivity analysis, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.03–1.44), stroke (aHR 1.68, 95% CI 1.06–2.68), and HF (aHR 1.31, 95% CI 1.15–1.48) but not AF (aHR 1.12, 95% CI 0.99–1.27). Conclusions: This study indicates that patients with a diagnosis of depression were more likely to develop cardiovascular disease, even if they had no known history of cardiovascular disease. Providers should include the treatment of depression as a part of a holistic approach to cardiovascular disease prevention.

Abstract 4145876: Prognostic significance of somatic mutations in myeloid cells of men with chronic heart failure – interaction between loss of Y chromosome and clonal hematopoiesis

Introduction: Age-associated clonal hematopoiesis of indeterminate potential (CHIP) has been associated with increased incidence and worse prognosis of chronic heart failure. CHIP is driven by somatic mutations in hematopoietic stem and progenitor cells (HSPC). Mosaic loss of the Y chromosome (LOY), the most common somatic mutation in blood cells of men, also correlates with clonal expansion of myeloid cells, increases with age and was experimentally shown to lead to diffuse cardiac fibrosis and subsequent heart failure in mice. However, the prognostic significance of LOY as well as its potential interaction with CHIP in patients with chronic heart failure is unknown. Aims/Methods: We investigated the prevalence and prognostic significance of the extent of LOY and the two most common CHIP-driver mutations DNMT3A and TET2 in 705 male patients with established chronic heart failure across the entire spectrum of left ventricular ejection fraction. Results: Both, LOY and DNMT3A/TET2 mutations, increased with age, and LOY co-occurred with DNMT3A/TET2 mutations in 27.1% of men at age &gt; 70 years. LOY was an independent predictor of death during 3-years of follow-up across the entire spectrum of left ventricular ejection fraction. The co-occurrence of harboring LOY and DNMT3A/TET2 mutations significantly contributed to the observed increased mortality observed in carriers of DNMT3A/TET2 mutations. The detrimental effect of LOY on prognosis was confirmed in a validation cohort of patients with ischemic heart disease.scRNA sequencing of peripheral blood cells in patients with chronic ischemic heart failure showed increased profibrotic signaling in LOY monocytes with elevated markers of monocyte mediated inflammation and profibrotic cardiac remodeling (S100A8, TLR2, CLEC4D) and reduced expression of TGF-b inhibiting genes (SMAD7, TGIF2). The proinflammatory phenotype of LOY monocytes was further amplified in LOY monocytes of patients simultaneously harboring DNMT3A mutations, who displayed heightened expression of alarmins (S100A8, HMGB2) and interferon signaling related genes (IFNGR1, TRIM56, CD84) compared to patients without CHIP mutations. Conclusion: The age-associated acquisition of somatic mutations in blood cells of men with chronic heart failure is associated with increased mortality, with loss of Y chromosome emerging as an independent predictor of all-cause death across the entire spectrum of left ventricular function.

Abstract 4124709: Accelerometer-Measured Sedentary Behavior and Future Cardiovascular Disease

Background: Current consensus guidelines emphasize the importance of achieving 150 minutes or more of moderate to vigorous physical activity (MVPA) per week to promote cardiovascular health but give little guidance about sedentary behavior. Research Question: Is sedentary behavior associated with cardiovascular (CV) disease in a manner distinct from insufficient physical activity? Aims: Examine associations between accelerometer-measured sedentary behavior with risk of specific CV outcomes, including potential interactions with MVPA. Methods: Using 89,530 individuals providing one week of accelerometer-based physical activity data from the UK Biobank, we fit Cox models adjusted for demographic and lifestyle factors to assess associations between sedentary time (as a spline term) and incident atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF), and CV mortality. We assessed the potential effect of MVPA on these associations by including MVPA as an adjustment variable, as well as performing subgroup analyses stratified at the guideline-recommended MVPA threshold. Results: Among 89,530 individuals (age 62±8 years, 56.4% women) undergoing accelerometry, median sedentary time was 9.4 hours/day (quartile-1: 8.2, quartile-3: 10.6). In multivariable models, using the second quartile (8.2-9.4 hours/day) as a referent, sedentary time in the top quartile (&gt;10.6 hours/day) was associated with greater risk of HF (hazard ratio [HR] 1.45, 95% CI 1.28-1.65), and CV mortality (HR 1.62, 95% CI 1.34-1.96), with evidence of a threshold effect at 10.6 hours/day. Higher sedentary time was also associated with greater risk of incident AF (HR 1.11, 95% CI 1.01-1.21) and MI (HR 1.15, 95% CI 1.00-1.32), with an approximately linear relation. Associations with HF and CV mortality persisted after adjustment for MVPA, as well as among individuals both above and below the guideline-based activity threshold of ≥150 minutes MVPA/week. Conclusions and Relevance: Sedentary behavior is broadly associated with future adverse CV outcomes. For HF and CV mortality, associations appear distinct from insufficient MVPA, and sedentary time in excess of 10.6 hours/day conferred an increased risk.

Type 2 diabetes pathway-specific polygenic risk scores elucidate heterogeneity in clinical presentation, disease progression and diabetic complications in 18,217 Chinese individuals with type 2 diabetes.

Type 2 diabetes is a complex and heterogeneous disease and the aetiological components underlying the heterogeneity remain unclear in the Chinese and East Asian population. Therefore, we aimed to investigate whether specific pathophysiological pathways drive the clinical heterogeneity in type 2 diabetes. We employed newly developed type 2 diabetes hard-clustering and soft-clustering pathway-specific polygenic risk scores (psPRSs) to characterise individual genetic susceptibility to pathophysiological pathways implicated in type 2 diabetes in 18,217 Chinese patients from Hong Kong. The 'total' type 2 diabetes polygenic risk score (PRS) was summed by genome-wide significant type 2 diabetes signals (n=1289). We examined the associations between psPRSs and cardiometabolic profile, age of onset, two glycaemic deterioration outcomes (clinical requirement of insulin treatment, defined by two consecutive HbA1c values ≥69 mmol/mol [8.5%] more than 3 months apart during treatment with two or more oral glucose-lowering drugs, and insulin initiation), three renal (albuminuria, end-stage renal disease and chronic kidney disease) outcomes and five cardiovascular outcomes. Although most psPRSs and total type 2 diabetes PRS were associated with an earlier and younger onset of type 2 diabetes, the psPRSs showed distinct associations with clinical outcomes. In particular, individuals with normal weight showed higher psPRSs for beta cell dysfunction and lipodystrophy than those who were overweight. The psPRSs for obesity were associated with faster progression to clinical requirement of insulin treatment (adjusted HR [95% CI] 1.09 [1.05, 1.13], p<0.0001), end-stage renal disease (1.10 [1.04, 1.16], p=0.0007) and CVD (1.10 [1.05, 1.16], p<0.0001) while the psPRSs for beta cell dysfunction were associated with reduced incident end-stage renal disease (0.90 [0.85, 0.95], p=0.0001) and heart failure (0.83 [0.73, 0.93], p=0.0011). Major findings remained significant after adjusting for a set of clinical variables. Beta cell dysfunction and lipodystrophy could be the driving pathological pathways in type 2 diabetes in individuals with normal weight. Genetic risks of beta cell dysfunction and obesity represent two major genetic drivers of type 2 diabetes heterogeneity in disease progression and diabetic complications, which are shared across ancestry groups. Type 2 diabetes psPRSs may help inform patient stratification according to aetiology and guide precision diabetes care.

Abstract 4116714: Macrophage Colony Stimulating Factor as a Causal Metabolic Mediator of Cardiovascular Disease: An Observational and Mendelian Randomization Analysis

Background: Macrophage biology plays a key role in the pathogenesis of atherosclerosis and circulating macrophage colony-stimulating factor (M-CSF) is a marker of macrophage activity. However, there is conflicting evidence regarding its role as a mediator of cardiovascular disease. Methods: We evaluated the association between plasma M-CSF concentration with myocardial infarction, stroke, heart failure and mortality in a large substudy involving 9992 participants drawn from 14 countries and followed for a median period of 9.8 years (Interquartile Range 8.9 years - 11.4 years) utilizing a nested case-cohort design in the Prospective Urban Rural Epidemiology (PURE) study. We then conducted a two-sample Mendelian randomization (MR) analysis to evaluate the upstream determinants (using genome wide association data from the PURE biobank and publicly available consortia) and downstream effects on clinical events.. Results: The strongest causal upstream determinant of M-CSF concentration was body mass index (BMI), which showed a positive association with plasma M-CSF concentration (Beta: 0.17 SD increase; 95% CI: 0.08 - 0.27). In a survival analysis, M-CSF was independently associated with increased incident myocardial infarction (HR: 1.25 per 1 SD M-CSF increase; 95% CI: 1.13-1.38), stroke (HR: 1.17; 95% CI:1.04-1.32), and heart failure (HR: 1.34; 95% CI: 1.15-1.56) and other cardiovascular disease risk factors. Circulating M-CSF concentration also showed a strong association with long-term risk of overall mortality (HR: 1.44; 95% CI: 1.39-1.60). Mendelian randomization analyses confirmed that increased M-CSF was associated with increased risk of MI, heart failure, and ischemic stroke (specifically large artery atherosclerotic and cardioembolic stroke). Conclusions: M-CSF is a strong causal driver of cardiovascular disease morbidity whose concentration is causally influenced by body mass index. Our analysis suggests a role for macrophage activity in mediating the relationship between body mass index and cardiovascular disease 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.

Long-term risk of heart failure in patients with postoperative atrial fibrillation following non-cardiac surgery: Insights from a nationwide cohort.

Atrial fibrillation (AF) is associated with heart failure (HF). However, it is unclear if postoperative AF (POAF) following non-cardiac surgery differs from non-surgical AF in terms of the risk of HF. We compared the long-term rate of incident HF in patients developing new-onset POAF following non-cardiac surgery with patients who did not develop POAF following non-cardiac surgery and patients with non-surgical non-valvular AF (NVAF). Using Danish nationwide registries, all patients aged ≥30 years who developed POAF following non-cardiac surgery (1996-2020) were identified and matched in a 1:3 ratio by age, sex, surgery type (only for the surgery group), selected comorbidities, and inclusion year with patients without POAF following non-cardiac surgery and individuals with NVAF, respectively. A total of 2270 patients with POAF were matched with 6810 patients without POAF following non-cardiac surgery, and 1846 patients with POAF were matched with 5538 patients with NVAF. The median follow-up was 7.2 years. Compared with patients without POAF, those with POAF had a higher associated long-term rate of incident HF (2.6 vs. 1.2 events per 100 person-years; adjusted hazard ratio [HR] 2.39, 95% confidence interval [CI] 2.06-2.78). Compared with individuals with NVAF, patients with POAF did not have a significantly different rate of incident HF (2.7 vs. 3.0 events per 100 person-years; adjusted HR 0.89, 95% CI 0.78-1.03). Patients with new-onset POAF following non-cardiac surgery had a higher associated long-term rate of incident HF compared to those without POAF, with no significant difference in the rate of incident HF when compared to patients with NVAF.

Abstract 4137836: Association of AHA PREVENT Risk Score with Cardiovascular Mortality Across Social Determinants of Health: A Nationwide Retrospective Cohort Study

Introduction/Background: The AHA PREVENT risk calculator was recently developed to accurately predict the risk of cardiovascular disease (CVD) risk, including incident heart failure, stroke, and coronary heart disease. However, the risk prediction of this tool for CVD mortality overall and among groups with increasing social determinants of health (SDOH) burden in a multi-ethnic nationally representative cohort of American adults is unclear. Methods: This retrospective study included adult NHANES participants (age &gt; 30 years) from 1998-2018 cycles without known CVD. Individuals without data for risk estimation were excluded. AHA PREVENT risk was scored from 0 to 100. Multivariable-adjusted Cox regression models were used to estimate the risk of CVD mortality, accounting for 7 SDOH measures (employment, family income, food security, health access, health insurance, housing instability, and being married or living with partner). Population was stratified based on cumulative SDOH burden (1, 2, 3, 4, 5, &gt; 5 unfavorable SDOH markers). Model discrimination was assessed using C-statistics in these groups. Results: Among 19,887 participants (median age 53 years, 49% Female, 54% White, 19% Black), a 1% increase in AHA PREVENT Risk score calculation was associated with 13% higher risk of CVD mortality (HR adj 1.13, 95% CI: 1.12-1.14) with C-statistic of 0.91. While AHA PREVENT Risk score was predictive of CVD mortality across the SDOH burden strata, there was a decline in C-statistic from 0.91 among those without any unfavorable SDOH to 0.81 among those with &gt; 5 unfavorable SDOH measures. Conclusion: The AHA PREVENT Risk score is predictive of CVD mortality even when accounting for SDOH measures. However, the risk discrimination decreases among individuals with a higher SDOH burden. Further investigation is needed to identify means to improve CVD risk prediction among disadvantaged people with high unfavorable SDOH burden.

Abstract 4117922: The Role of Combined Renin Angiotensin Aldosterone System Inhibitors (RAASi) Plus Beta Blocker Therapy For Cardiotoxicity Prevention In Patients Under Chemotherapy For Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

Introduction: Anti-neoplastic agents, including anthracyclines and trastuzumab, frequently employed in breast cancer treatment carry on considerable cardiotoxic effects impairing both cardiac chamber and cardiac fiber parameters leading to incident heart failure. In response to this challenging side effect, numerous randomized controlled trials (RCTs) have investigated the cardioprotective efficacy of RAASi and beta-blockers (BBs) in patients undergoing anthracycline and trastuzumab chemotherapy. We aim to perform an updated meta-analysis to elucidate the potential cardioprotective properties of these medications in patients undergoing chemotherapy for breast cancer. Methods: A comprehensive search of the literature was performed through April 2024 on PubMed, EMBASE and Clinicaltrials.gov. In total, data from 4 randomized studies were extracted and analyzed. The primary analysis was the effect of RAASi and BBs on LVEF as well as global longitudinal strain (GLS). Data were analyzed using a random-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals for both LVEF and GLS. Data was analyzed using Review Manager 5.3 (RevMan 5.3) software. Results: In total, data from 248 patients (N = 124 on cardioprotection; N = 124 without cardioprotection) undergoing treatment with anti-neoplastic agents for breast cancer were included. At the end of treatment, patients undergoing cardioprotective therapy demonstrated improved LVEF preservation compared to the control group, (mean difference 2.14 [0.03, 4.25]; P=0.05; I2 = 79%). In addition, patients undergoing dual RAASi + BB therapy showed better GLS preservation compared to control group (mean difference –1.37 [-2.01, -0.72]; P &lt; 0.0001; I2 = 0%). Conclusion: In breast cancer patients undergoing anti-neoplastic regimens comprising anthracycline and trastuzumab, the concomitant administration of RAASi and BBs demonstrated better LVEF as well as GLS preservation upon completion of treatment over those without cardioprotective therapy. These findings shed light on the potential benefit derived from the synergistic effects of RAASi and BBs therapy in safeguarding both cardiac chamber and fiber functions amidst aggressive anti-cancer regimens, although further investigations still need to be conducted.