Heart Failure Mortality Research Articles

Abdominal Compared With Coronary Artery Calcification and Incident Cardiovascular Events and Mortality in Black Adults.

Black adults show heightened cardiovascular risk compared with other groups despite comparable or lower coronary artery calcium (CAC) scores, indicating potential cardiovascular risk underestimation by CAC. Abdominal aortic calcification (AAC), preceding CAC, may predict cardiovascular events better in Black adults who are prone to early atherosclerotic cardiovascular disease and excess events at low CAC scores. We included 2551 participants from the JHS (Jackson Heart Study) visit 2 examination (2005-2008) without cardiovascular disease, followed through 2016. Cox regression estimated hazard ratios for incident cardiovascular events defined as a composite of myocardial infarction, stroke, heart failure, and all-cause mortality. The predictive value of CAC and AAC, when added to the American College of Cardiology/American Heart Association cardiovascular risk algorithm (pool cohort equation), was assessed. Mean age was 57±10 years; 66% were women. Over a follow-up period of 12.6 years, 287 (11.3%) cardiovascular events and 360 (14.1%) mortality cases were observed. Adjusting for demographic and clinical variables, each 2-fold increase in CAC and AAC was associated with cardiovascular events (CAC: hazard ratio, 1.10 [95% CI, 1.06-1.13]; AAC: hazard ratio, 1.10 [95% CI, 1.06-1.13]) and all-cause mortality CAC: hazard ratio, 1.04 [95% CI, 1.01-1.08]; AAC: hazard ratio, 1.05 [95% CI, 1.01-1.08]). The incremental value of CAC (0.17 [95% CI, 0.08-0.23]) and AAC (0.15 [95% CI, 0.07-0.29]) to the pool cohort equation by net reclassification index was comparable. Notably, 45% of participants with 0 CAC showed some degree of AAC. Each 2-fold increase in AAC was associated with an increased risk of cardiovascular events (hazard ratio, 1.07 [95% CI, 1.01-1.19]) but not all-cause mortality among participants with 0 CAC. AAC is comparable to CAC in predicting cardiovascular events and all-cause mortality among Black adults, potentially valuable when CAC is absent.

Beta-Blockers and Mortality Reduction in Heart Failure: A Systematic Review of Randomized Controlled Trials

Background: Heart failure is a leading cause of morbidity and mortality. This systematic review evaluates beta blockers' effects on all-cause mortality, cardiovascular mortality, and hospital admissions in heart failure, synthesizing data from over 50 randomized controlled trials. Methods: Using PRISMA principles, the data regarding the effect of beta blockers on heart failure mortality and hospitalizations were synthesized. Extensive database searches (PubMed, Embase, Cochrane Library, and Web of Science) and manual reference checks were used to identify randomized controlled studies that compared beta blockers with placebo or conventional treatment in adults. The quality of data extraction process was evaluated according to the Cochrane Risk of Bias tool following the guidelines. Heterogeneity was assessed (I2), sensitivity analyses guaranteed robustness, and random-effects meta-analyses quantified results. Transparency was guaranteed via PROSPERO registration. Results: Beta-blockers were linked to a 29% decrease in cardiovascular mortality (OR 0.71, 95% CI 0.64–0.79, p< 0.05) and a 33% decrease in all cause mortality (OR 0.67, 95% CI 0.59–0.76, p < 0.05) when compared to alternative therapies. Additionally, beta-blocker-treated patients saw a 37% decrease in hospital admissions (OR 0.63, 95% CI: 0.56–0.71, p < 0.05). The class impact of beta blockers in heart failure treatment is supported by these advantages which were constant across subgroups and beta blocker types. Conclusion: This systematic review corroborates the well-established benefit of beta blockers in lowering mortality and hospitalizations in heart failure patients, particularly with HFrEF. The findings support the use of beta blockers as a cornerstone of heart failure therapy and there is a need for further research to optimize the use of beta blockers in combination with other emerging therapies.

Mesenchymal precursor cells reduce mortality and major morbidity in ischaemic heart failure with inflammation: DREAM-HF.

Progressive heart failure with reduced ejection fraction (HFrEF) is adversely affected by alterations in the myocardial balance between bone marrow-derived pro-inflammatory cardiac macrophages and embryo-derived reparative cardiac resident macrophages. Mesenchymal precursor cells (MPCs) may restore this balance and improve clinical outcomes when inflammation is present. The purpose was to (i) identify risk factors for cardiovascular death (CVD) in control patients with HFrEF in the DREAM-HF trial, and (ii) determine if MPCs improve major clinical outcomes (CVD, myocardial infarction [MI], stroke) in high-risk patients with ischaemic HFrEF and inflammation. Cause-specific regression analyses were used to identify CVD risk factors in DREAM-HF control patients. Aalen-Johansen cumulative incidence curves were used to examine CVD, 2-point major adverse cardiovascular events (MACE) (MI or stroke), and 3-point MACE (CVD or MI or stroke) by treatment group in ischaemic vs non-ischaemic HFrEF and in patients with or without baseline inflammation. In control DREAM-HF patients, factors portending the greatest risk for CVD were inflammation (baseline plasma high-sensitivity C-reactive protein ≥2 mg/L; p = 0.003) and ischaemic HFrEF aetiology (p = 0.097), with increased CVD risk of 61% and 38%, respectively. Over 30-month mean follow-up, MPCs reduced 2-point and 3-point MACE by 88% (p = 0.005) and 52% (p = 0.018), respectively, in patients with ischaemic HFrEF and inflammation compared to controls. Ischaemic aetiology and inflammation were identified as major risk factors for MACE in control DREAM-HF patients. A single intramyocardial MPC administration produced the most significant, sustained reduction in 2-point and 3-point MACE in patients with ischaemic HFrEF and inflammation.

Association between iron deficiency and risk of major events in chronic kidney disease

Iron deficiency (ID) is common in patients with chronic kidney disease (CKD) but remains under-diagnosed and its prognosis poorly documented in the absence of anemia. The aim of the study was to assess the relationship between ID and the risk of major adverse outcomes in patients with CKD. Using data from the French Chronic Kidney Disease - Renal Epidemiology and Information Network (CKD-REIN) cohort which included and followed over five years, 3,033 patients with CKD stages 2 to 5 CKD, we estimated the prevalence of ID, defined by a ferritin level < 100 mg/L and/or a transferrin saturation < 20%, and associated hazard ratios (HR) of kidney failure with replacement therapy, kidney failure defined by an eGFR < 15 mL/min per 1.73 m2 or initiation of kidney replacement therapy, all-cause mortality, and death or hospitalization for heart failure. Baseline prevalence of ID in the cohort (66% men; mean age 67 ± 13 years) was 50% (48-52). Mean hemoglobin was 13 ± 1.7 g/dL, and only 31% of patients with ID also had a hemoglobin < 12 g/dL. In 2,803 patients with CKD stages 2-4 at baseline, ID was associated with significant increased risk of kidney failure, and of kidney failure with replacement therapy, with HRs adjusted for confounders and hemoglobin level of 1.22 (1.03-1.45) and 1.57 (1.27-1.94), respectively. Adjusted HRs for all-cause mortality and hospitalization or death for heart failure, were 1.31 (1.04-1.66) and 1.38 (1.07-1.80), respectively. This study shows that ID is significantly associated with the risk for kidney failure, all-cause mortality, and heart failure, independent of the presence of anemia.

Impact of implantable cardioverter defibrillators on mortality in heart failure receiving quadruple guideline-directed medical therapy: a propensity score-matched study

BackgroundIn the contemporary management of heart failure with reduced ejection fraction (HFrEF), the recommended quadruple guideline-directed medical therapy (GDMT) consists of angiotensin receptor-neprilysin inhibitor (ARNI), evidence-based beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i). This study explored the impact of adding implantable cardioverter-defibrillator (ICD) therapy to this comprehensive regimen in HFrEF patients.MethodsUtilizing deidentified data from the National Electronic Database of the Turkish Ministry of Health, we conducted a nationwide retrospective cohort study on 5450 HFrEF patients receiving quadruple GDMT, including ARNI. Among them, 709 patients underwent additional ICD or cardiac resynchronization therapy defibrillator (CRT-D) implantation. Propensity score matching ensured balanced baseline characteristics between groups. Primary endpoint was determined as all-cause mortality.ResultsIn the matched cohort, all-cause mortality occurred in 108 out of 619 patients (17.4%) in the GDMT group and 101 out of 619 patients (16.3%) in the ICD group, with a hazard ratio (HR) of 0.74 and a 95% confidence interval (CI) ranging from 0.57 to 0.98. The median follow-up time was 1365 days in the matched cohort, 1283 days in the GDMT group. Subgroup analyses consistently demonstrated benefits, particularly among individuals aged 61 years and older (HR: 0.60, 95% CI: 0.42–0.87, p = 0.006), those with sinus rhythm (HR: 0.55, 95% CI: 0.34–0.89, p = 0.013), individuals not using amiodarone (HR: 0.61, 95% CI: 0.42–0.89, p = 0.011), and those with an estimated glomerular filtration rate lower than 61.9 (HR: 0.66, 95% CI: 0.48–0.91, p = 0.011).ConclusionsThis study may offer a glimmer of hope that even after achieving the best current optimal medical therapy, the addition of device therapy could still yield positive outcomes in the management of patients with HFrEF.Graphical

Predictive Analytics in Heart Failure Risk, Readmission, and Mortality Prediction: A Review

Predictive Analytics in Heart Failure Risk, Readmission, and Mortality Prediction: A Review

Forecasting heart failure: Seasonal alignment of heart failure outcomes in New York.

Seasonal variations have been observed in heart failure (HF) hospitalization. Numerous explanatory mechanisms have been proposed, but no prior studies have examined potential contributors directly. Our objective was to identify specific factors that could contribute to seasonal variability using a large longitudinal dataset of HF hospitalizations. Hospital discharge data were obtained for all hospitals in the state of New York from 1994 to 2007. Records with a primary diagnosis of HF by the International Classification of Diseases-9 Clinical Modification (ICD-9-CM) code (428.xx and 425.xx) were included. Year and month of admission were used as predictors to evaluate outcomes of in-hospital mortality, population-adjusted daily rate of hospital admissions and length of stay (LOS) using univariable regression including a sinusoidal model to assess the seasonality of HF outcomes. Observations were then adjusted for multiple medical covariables as well as the average local monthly temperature and humidity at each hospital using data from the Global Historical Climate Network to identify potential modifiers of seasonal variability. Among 949907 records, the median age was 76 [inter-quartile range (IQR) 65-84years old], and the cohort was 54% female (510945 records). The population-adjusted rate of HF admissions per day increased by 1.1 admissions/day/year between 1994 and 2007, whereas in-hospital mortality and LOS decreased by -0.3%/year and -0.3days/year, respectively (P<0.001 for all). Seasonal trends were identified for daily HF admissions (February peak, P<0.0001), mortality (January peak, P<0.001) and LOS (January peak, P<0.01). Cosinor analysis revealed significant periodicity for HF admission rate (amplitude=±0.9 admissions/day/100000 people, P<0.001), in-hospital mortality (amplitude=±0.47%, P<0.001) and LOS (amplitude=±0.23days, P<0.01). No other patient characteristics were significant modifiers of seasonality. Odds of mortality were highest in July rather than January when adjusted for average local temperature but not humidity. Adverse outcomes in patients hospitalized with HF were significantly worse in the winter months even when adjusted for patient characteristics and concurrent acute diagnoses such as pneumonia. Local ambient temperature was the strongest modifier of the observed seasonality. Given the increasing frequency of extreme weather events, additional work to determine the mechanisms of this and other environmental risk factors is urgently needed.

Abstract 4148077: Heart Failure Mortality Between 1990 and 2020 by US State and Racial and Ethnic Group

Introduction: Heart failure (HF) mortality rates in the US appear to have increased in the past decade. It is unknown how these have changed in recent years by racial and ethnic groups within states. Research Question: To understand disparities in HF mortality patterns between 1990 and 2020 Aim: To estimate the change in HF mortality rates between 1990 and 2020 for Hispanic, non-Hispanic Black, and non-Hispanic White males and females in each US state Methods: We used multiple cause of death records from the National Vital Statistics System and population data from the National Center for Health Statistics to estimate HF mortality from 1990 to 2020 by state, age group, sex, and racial and ethnic group. A binomial model was fit to the data using RegMod, a Bayesian extension of a generalized linear model which incorporated priors from a hierarchy and modeled year as a spline. Results: In 2020, we estimated 566230 (95% UI 566160 to 569740) deaths due to HF. Between 1990 and 2010, HF rates declined in general for all racial and ethnic groups across the US, but not consistently for all states (Figure). From 2010 to 2020, this trend reversed, with age-standardized mortality from HF increasing over this time period, but again this change was not consistent across states. Among the Hispanic population, mortality increased for all states except for Maine, with the largest change for both sexes in Oklahoma. For the non-Hispanic, Black group, mortality increased among all states, with the largest change for both sexes in Oklahoma and South Dakota. Among the non-Hispanic, White populations, mortality decreased for both sexes in District of Columbia, while the largest increases were in Oklahoma. Conclusion: Heart failure mortality increased in the past decade, with striking increases in specific locations by race and ethnic group. Identifying etiologies and drivers of increased HF deaths, including the role of new therapies for subsets of systolic function, could help target novel therapies to subpopulations at highest risk. Differences in trends by state and race and ethnicity groups provides important information for clinicians and policymakers interested in reducing mortality rates.

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.

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 4122247: Impact of serum chloride levels for ventricular arrhythmias in patients with heart failure undergoing cardiac resynchronization therapy

Background: As previous reports of ventricular arrhythmia (VA) as a prognostic marker of mortality in heart failure (HF) patients included those with implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) devices, little is known about the risk factors of VA among patients undergoing cardiac resynchronization therapy (CRT), especially those without previous VA. The prognostic role of electrolyte abnormalities has been highlighted in HF patients. This study evaluated the impact of serum chloride levels for VA and all-cause death in patients with HF who underwent CRT without VA before CRT implantation. Methods: From the retrospective cohort of 397 HF patients (age 63+/-13, male 74%) who undergoing CRT implantation between 2010 and 2020, this study enrolled 175 patients (82% implanted CRT with a defibrillator) without a previous history of VA (sustained ventricular tachycardia (VT) of ventricular fibrillation (VF)). We studied the impact of serum chloride levels before CRT implantation. The primary endpoint was defined as VA, VA with ICD therapy and sudden cardiac death. The secondary endpoint was all-cause mortality. Results: During median follow-up of 35 months, 53 patients (30%) experienced VA. Patients with VA had a tendency toward high LVESV (172ml vs. 150ml, p&lt;0.09) and low left ventricular ejection fraction (26 vs. 29, p&lt;0.09), and significantly reduced rate of angiotensin converting enzyme inhibitors or angiotensin receptor blockers (30% vs. 70%, p&lt;0.05) at the time of CRT implantation. The rate of CRT responders was significantly higher in patients without VA than with VA (59% vs. 40%, p&lt;0.05). The cut-off value of chloride for VA was determined to be 102mEq/l using receiver operating characteristic analysis. The patients with chloride ≤102mEq/l had significantly higher rates of VA (41% vs. 25%, log-rank p&lt;0.05) and mortality (33% vs. 18%, log-rank p&lt;0.05) (Figure). By multivariate cox analysis, the level of chloride had an independent predictive value of VA in patients with CRT (hazard ratio [HR] 1.08 per 1mEq/l decrease, 95% confidence interval [CI] 1.00-1.16, p&lt;0.05) (Table). Conclusions: The chloride level had a predictive value for VA after CRT implantation in HF patients without previous VA. The management of electrolytes, including chloride, might be important for preventing fatal arrhythmia in patients with HF undergoing CRT implantation.

Abstract 4145889: Association between Pulmonary Artery Elastance and all cause mortality in patients with Heart Failure: A Meta-Analysis

Background: Pulmonary Artery Elastance (PAE) is an echocardiographic value commonly calculated in Heart Failure (HF) patients. It is presumed to be associated with mortality and adverse outcomes. We aim to evaluate pulmonary artery elastance (PAE) as a predictor of all-cause mortality in heart failure (HF) patients Methods: A comprehensive literature review was conducted on PubMed and Google Scholar from inception till May 2024 for articles relevant to the mortality outcomes in HF patients with respect to pulmonary arterial elastance as one of their predictors. Data were extracted independently by four different reviewers. We used a fixed-effects model meta-analysis model to evaluate and pool the outcomes in association with PAE and all-cause mortality. Further assessment of the outcomes was performed by sensitivity analysis with a one-study removal method and meta-regression analysis. Results: Out of 63 studies, 4 studies with 759 patients were included in our meta-analysis. Mean age ranged from 54 to 65 years. We found there was a statistically significant association between pulmonary artery elastance and all-cause mortality (OR: 1.12, 1.06 - 1.19, p &lt; 0.0001] (Figure 1a). Sensitivity analysis with one-study removal showed overall effects in the meta-analysis still lean towards supporting PAE as the predictor for ACM (Figure 1b). Meta-regression analysis with age (Figure 1c), sex and other supportive variables did not show statistically significant associated confounders. Conclusion: This meta-analysis establishes a significant association between elevated PAE and increased risk for all-cause mortality in HF patients. These results suggest PAE could be a strong predictor for all-cause mortality in HF patients. Further research is needed to provide a more comprehensive understanding of the predictive value of PAE for HF patients. The association between PAE and mortality could provide significant insights that could influence clinical practice and improve patient outcomes in HF.

Abstract 4114198: Humanin Level is Inversely Correlated with NT-proBNP Level and Mortality in Heart Failure with Reduced Ejection Fraction

Background: Mitochondrial dysfunction contributes to heart failure (HF) progression via diminished energy supply, release of reactive oxygen species, and increased cell death. However, there has yet to be clinically relevant biomarkers that address mitochondrial-mediated cardiac injury in patients. Humanin (HN) is a mitochondria-derived peptide that protects cells through the interference of apoptosis and reduction of oxidative stress. The objectives of our study were to measure circulating plasma HN levels in patients with HF with reduced ejection fraction and describe the relationship of HN to validated, clinically relevant measures of HF. Methods: We conducted a prospective cohort study. To be included in the study, patients must have: 1) left ventricular ejection fraction &lt;40%, 2) high risk of future clinical instability, 3) medication and device treatment according to guidelines, and 4) stable medical therapy for at least 30 days prior to screening. Plasma HN levels were measured at time of study enrollment by an enzyme-linked immunoassay. Statistical analyses were performed to evaluate the relationships between HN levels and demographic variables, quantitative measures of HF, and clinical outcomes. Results: 54 HF patients were included in the study. Age and sex were not significantly associated with HN level. There was a significant difference in mean HN level by race with highest HN level seen in Caucasians and the lowest HN level seen in Hispanics (1310 pg/ml vs. 630 pg/ml, p=0.012). There was a significant inverse correlation between NT-proBNP level and HN level (r=-0.46, p &lt;0.001). After adjusting for race, higher NT-proBNP level, as both a continuous and categorical variable, was significantly associated with lower HN level. Furthermore, HN level was significantly lower in patients who died within 6 months compared to those who did not (520.7 pg/ml vs. 1146.9 pg/ml, p=0.013). After adjusting for race, lower HN level was significantly associated with increased odds of 6-month mortality (OR=0.784, 95% CI 0.620-0.943, p=0.018). Conclusions: To the best of our knowledge, this is the first study to describe plasma HN levels in HF patients. Its significant correlation with mortality and NT-proBNP level supports a potential role for HN as a novel prognostic biomarker in HF with reduced ejection fraction.

Abstract 4122048: Disparities in Heart Failure-Related Mortality Among Reproductive-Aged Women in the United States from 1999 to 2019

Introduction: Heart failure (HF) majorly affects the elderly, but can also affect the younger population. This study aims to examine the trends of HF-related deaths among reproductive-aged women in the United States (US). Method: We conducted a retrospective analysis using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database, extracting data through ICD-10 codes I11, I13.0, I13.2, and I50 to find HF-related deaths among women aged 15-44 from 1999 to 2019. We examined demographic disparities in HF mortality rates over time, considering age, ethnicity, and geographic areas. Results were reported as age-adjusted mortality rate (AAMR) and 95% confidence interval (CI). Joinpoint regression assessed trend changes and annual percentage change (APC). Results: Between 1999 and 2019, a total of 43,683 women aged 15-44 died from HF in the US, with an AAMR of 3.5 per 100,000 (95% CI: 3.5-3.5). The AAMR increased from 2.6 in 1999 to 4.8 in 2019. Non-Hispanic Black women had the highest AAMR at 10.2, while Hispanics had the lowest at 1.8. Geographically, the South was the most affected region with an AAMR of 4.6, contributing to nearly half (48.9%) of all deaths. States including Massachusetts, Oregon, New Hampshire, and Minnesota had the lowest AAMRs. Rural areas showed a higher AAMR compared to urban areas (4.4 Vs. 3.3). The age group (35-44) accounted for the majority of deaths (73.7%). Conclusion: HF-related mortality among reproductive-aged women increased from 1999 to 2019, with the highest burden among non-Hispanic Black women and those in the Southern region. Enhancing access to care, particularly in rural areas, and implementing targeted prevention programs are vital to reducing mortality rates.

Abstract 4137718: Coronary Artery Calcium for Risk Stratification of Heart Failure Mortality

Background: There is increasing interest in predicting heart failure (HF), a major cause of morbidity and mortality that exerts a significant financial burden. The role of coronary artery calcium (CAC), an accessible and inexpensive test, in predicting long-term HF mortality amongst asymptomatic adults remains unknown. Objectives: To determine if CAC burden is associated with HF-related mortality in the primary prevention population. Methods: The study included 66,636 primary prevention patients from the Coronary Artery Calcium Consortium. Multivariable competing risks regression was used to assess the association between CAC and HF-related mortality adjusting for demographics and traditional risk factors. Results: The mean age was 54.4 years, 67% male, 89% white, and 55% had CAC &gt;0. A total of 260 HF-related mortality events were observed during a median follow up of 12.5 years, 75.3% of which occurred among those with a baseline CAC score &gt;100. Compared with a CAC = 0, there was a stepwise higher risk (P &lt; 0.005) of HF mortality for CAC 1-100 (subdistribution hazard ratio [SHR]: 2.27; 95% CI: 1.3-3.99), 100-400 (SHR: 3.68; 95% CI 2.1-6.43), and &gt;400 (SHR: 7.05; 95% CI 4.05-12.29). This increasing risk of HF mortality across higher CAC scores persisted across age groups, sex, and in the intermediate and high-risk groups as calculated by the pooled cohort equation (PCE) and the PREVENT equation. Conclusions: Higher CAC is associated with increasing incidence of long-term HF-related mortality in the primary prevention population, particularly intermediate and high-risk patients. Early preventive approaches in patients with high CAC must focus on preventing heart failure and ASCVD with lifestyle changes and medications.

Abstract 4125157: Efficacy of Adding Sodium-Glucose Co-Transporter 2 Inhibitor versus Standard Therapy Alone in Post-Percutaneous Coronary Intervention Patients: A Systematic Review and Meta-Analysis

Background: Recent evidence suggests that sodium-glucose cotransporter-2 inhibitors (SGLT2-i) may improve outcomes in patients with coronary artery disease (CAD) through various physiological pathways. However, their impact on patients who have undergone percutaneous coronary intervention (PCI) is not well established. This meta-analysis aims to evaluate the effectiveness of additive SGLT2 inhibitors versus standard therapy alone in patients with CAD after PCI. Methods: A systematic search was conducted across the Medline, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) and observational studies that compared the addition of SGLT2 inhibitors to standard therapy versus standard therapy alone in patients post-PCI. The outcomes analyzed were Major Adverse Cardiovascular Events (MACE), all-cause death, cardiovascular death, recurrent acute myocardial infarction (AMI), nonfatal stroke, revascularization, and hospitalization for heart failure (HF). Results: A total of 7 studies met the inclusion criteria, encompassing a total of 11,800 individuals (5,004 on SGLT2-i and 6,796 non-SGLT2-i; mean age of 62.7 years; 28% women; 95% diabetic patients). SGLT2 inhibitors significantly reduced the risk of all-cause mortality (RR 0.6, 95% CI: 0.5-0.72, p&lt;0.01), cardiovascular death (RR 0.39, 95% CI: 0.16-0.94, p=0.03) and hospitalization for HF (RR 0.55, 95% CI: 0.4-0.76, p&lt;0.01) compared to standard therapy alone. The occurrence of the composite endpoint (MACE) (RR 0.67, 95% CI: 0.44-1.01, p=0.056), any revascularization (RR 0.93, 95% CI: 0.57-1.53, p=0.784), recurrent AMI (RR 0.70, 95% CI: 0.41-1.18, p=0.176) and stroke (RR 0.94, 95% CI: 0.68-1.30, p=0.717) did not differ significantly between groups. Conclusions: Adding SGLT2 inhibitors to standard therapy significantly improved cardiovascular outcomes in patients with CAD who have undergone PCI, including reduced mortality and hospitalization for HF rates, with similar rates of recurrent AMI, coronary revascularization and stroke. These findings support the consideration of adding SGLT2 inhibitors as part of the therapeutic regimen for post-angioplasty patients, especially those with diabetes.

Abstract 4134957: Survival and Cardiac Recovery in Pediatric Dilated Cardiomyopathy: A Long-term Cohort Study of Risk Factors, Prognosis, and Health Outcomes Followed into Adulthood

Background: Dilated cardiomyopathy (DCM) is the most common cause of pediatric heart failure (HF), but there is limited literature on its long-term prognosis and treatment outcomes. We examined risk factors for long-term morbidity and mortality and outcomes of care in childhood-onset DCM. Methods: Electronic medical records from a tertiary care pediatric hospital (SickKids, Toronto, Canada) were used to retrospectively follow children ages 0–18 years with DCM from January 1, 2001 to July 1, 2017. Provincial healthcare administrative data was used to monitor outcomes recorded outside of SickKids, following patients during the same time period and into adulthood (age &gt;18 years) until August 31, 2023. We compared DCM cases, with or without echocardiographic recovery (LVEDD z score &lt; 2 and LVEF ≥ 55%), and controls matched on sex, age, and urban/rural residence on a range of health and health service outcomes. Primary outcomes included all-cause mortality, heart transplant (HT), and inpatient admission for HF. Among cases, Cox proportional hazards regression with backwards selection was used to identify demographic, disease, and treatment characteristics associated with each primary outcome, with candidate variables selected based on univariate analysis and clinical judgment. Results: We studied 156 patients with DCM and 780 controls for a median of 14.8 years. Median age at the end of follow-up was 16.2 years. Compared with controls, DCM cases had higher rates of all-cause death, HT, and HF admission (all P &lt;0.001), as well as chronic kidney disease ( P &lt;0.001) and diabetes ( P =0.002). Compared to cases with recovered DCM (n=53), non-recovered cases had higher rates of death, HT, and HF admission (all P &lt;0.001). On multivariable analysis, beta blockers were associated with reduced mortality risk (HR 0.343, 95% CI 0.162–0.727). Using any HF medication (HR 0.205, 95% CI 0.102–0.412) and living in an urban versus a rural area (HR 0.166, 95% CI 0.048–0.573) decreased HT risk. Idiopathic (HR 4.16, 95% CI 1.42–12.2) or sarcomeric mutation-related (HR 9.86, 95% CI 2.30–42.3) DCM were associated with higher HT risk than myocarditis-related DCM. Conclusions: While childhood DCM is associated with long-term adverse health and increased health care utilization, patients who recover have improved morbidity and mortality. Treatment (e.g. medication or access to urban specialist care) was associated with lower mortality and HT risk in DCM.

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

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

Abstract 4138545: Mitral Valve Replacement is associated with favourable Functional and Clinical Outcome as compared with Restrictive Mitral Annuloplasty in Patients with Severe Ischemic Mitral Regurgitation. A prospective longitudinal analysis

Background: Restrictive mitral annuloplasty (RMA) and chordal-sparing mitral valve replacement (MVR) are common options for treatment of chronic severe ischemic mitral regurgitation. Research question: in patients with severe ischemic mitral regurgitation the most effective surgical approach remains controversial Aim: to test whether MVR provides superior clinical and functional outcomes compared with RMA. Methods: a prospective longitudinal analysis on 187 patients (age: 66 ± 9 year; EF:35 ± 8 %) undergoing MVR or RMA and CABG for severe ischemic mitral regurgitation. Six-minute walking test and echocardiography were performed at preoperative baseline, at 1 year and at a median FU of 5 year (interquartile range: 2.9). Brain natriuretic peptide levels were also obtained. Mitral regurgitation was defined through a comprehensive and integrative approach. Recurrent mitral regurgitation was defined as a vena contracta ≥ 3 mm at follow-up, in patients with no persistent regurgitation at discharge. The primary outcome was a 5-year composite of all-cause mortality and rehospitalization for heart failure. Survival analysis was performed with Kaplan-Meier method. Cox regression analysis was used to verify any independent predictor of composite end-point Results: Baseline preoperative data were similar between the two group. Mitral valve replacement was performed in 49% of patients (n=92) and RMA in 51 % (n=95). At 5 year patients referred to prostheses showed significant improvement in six-minute walking test as compared to RMA (MVR: 290 ± 70 meters vs MRA: 165± 56 meters) (p &gt; 0.01) ( Figure 1 ). The brain natriuretic peptide values did not differ between the two group at 1 year whereas were significantly lower in the MVR group at 5 years (MVR: 135 pg/ml; interquartile range:100 vs RMA: 486 pg/ml; interquartile range: 68 (p&lt;0.01) ( Figure 2 ). At 5 years freedom from all-cause death and rehospitalization for heart failure was higher in the MVR group as compared to RMA (84 ±8.9% vs 61 ±12%, p&lt;0.01) ( Figure 3 ). According to the Cox analysis recurrent mitral regurgitation was found to be a predictor of clinical outcome (HR:5.4, 95% CI:1.3-23.2, p= 0.023). Conclusions: In patients with severe ischemic mitral regurgitation referred for surgery, chordal- sparing MVR and CABG may improve functional capacity, clinical outcome and brain natriuretic peptide levels, compared with RMA and CABG. The impact of these findings remains to be defined by larger studies on longer term

Abstract 4119210: Differential Proteomic Expression of IGFßP-1 and IGFßP-2 in Primary Angioplasty for Acute Myocardial Infarction

Introduction: Insulin growth factor (IGF) binding protein-1 and 2 (IGFBP-1 and 2) are implicated in acute myocardial infarction (AMI) and have been suggested as predictors of mortality and development of heart failure. The IGF axis has been shown to play roles in cell proliferation and apoptosis. We analysed the serum IGFBP-1 and 2 levels in AMI before and after percutaneous coronary intervention (PCI) and correlated this with cardiac magnetic resonance (CMR) imaging to better establish their significance as biomarkers in AMI. Methods: Patients with AMI who presented to Royal Free Hospital, London, were recruited for proteomic analysis (O link Proximity Extension Immunoassay) at presentation, 24h and 72h following primary PCI. All underwent both admission and follow-up CMR at 6 months to assess for myocardial oedema, left ventricular volumes and function, and assessment of scar. Results: Proteomic evaluation in 20 AMI patients (male 95%; median age 59) revealed significant reduction in the average IGFBP-1 values at discharge compared with presentation, from 5.93 to 4.52 (24% reduction, p=0.003). Conversely, the average IGFBP-2 values at discharge significantly increased from 7.66 to 8.29 (8% increase, p=0.001). Higher discharge IGFBP-2 value was also correlated with increased indexed left ventricle end diastolic volume (LVEDV) at 6-month follow-up (R=0.54, p=0.032). Discussion: IGFBP-1 and 2 showed significant change following intervention for AMI. IGFBP-1 is a stress hormone, which is directly and indirectly activated by cytokines, dysglycaemia and vasopressin activation. Its subsequent reduction following PCI in AMI indicates relative resolution of inflammation, but this was not correlated with changes in infarct size or LV function at follow-up. IGFBP-2 showed significant upregulation, and higher values at discharge were significantly correlated with increased LDEDV at follow-up, suggesting adverse clinical outcomes within this setting. This data suggests differential roles of IGFBP-1 and 2 in the pathogenesis of AMI.