bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146122: Potential Protective Roles of Clonal Hematopoiesis of Indeterminate Potential in Angina Pectoris
Authors: Zheng Yidan , Zhou Zihao , Qian Xingyu , Hu Shiyan , Jingyu Xu , Liu Yuqi , Tong Fuqiang , Fan Pengning , chen zhe , Zhu Da , Pan Xiangbin , Dong Nianguo , Xu Li , Li Fei
Published: November 2024

Introduction:
Clonal hematopoiesis of indeterminate potential (CHIP) poses strong relationship to the occurrence of cardiovascular diseases with the process of aging. IL-1β is associated with both CHIP and atherosclerotic lesions stabilization. However, potential protective effects of CHIP and IL-1β elevation in angina pectoris have been barely explored.

Hypothesis:
We hypothesis CHIP protects against angina pectoris via preventing atherosclerotic lesions rupture by the effect of IL-1β.

Methods:
In UK Biobank population with exome sequencing data, participants with any CHIP or large CHIP were defined as those with variant allele fraction (VAF) ≥ 2% or 10% respectively on any CHIP gene. Angina pectoris, stable angina pectoris and unstable angina pectoris was defined as main diagnosis of inpatient record in terms of ICD-10 code I20, I20.8 and I20.0, respectively. The effects of CHIP on angina pectoris were estimated in logistic regression models, including age, sex, and history of atherosclerotic heart disease as covariates. Propensity score matching (PSM) of 1:1 was applied for more stringent analysis. Proteomics analysis was carried out using linear regression model.

Results:
Total 465769 participants were included for final analysis (aged 56.5±8.1 years, 45.7% male) after excluding those with hematological malignancy. Covariate-adjusted models showed that large CHIP significantly protected against angina pectoris (OR=0.863, p=0.019), especially the unstable angina pectoris subtype (OR=0.931, p=0.028). Both any CHIP and large CHIP of specific genes manifested significantly protective effects on angina pectoris (OR
any
=0.104, p<0.001; OR
large
=0.017, p<0.001) and unstable angina pectoris subtype (OR
any
=0.123, p<0.001; OR
large
=0.033, p<0.001) after PSM. Proteomic analysis showed IL-1β was significantly elevated among serum cytokines in CHIP population and positively associated with large CHIP (p=0.007).

Conclusion:
CHIP posed protective effects against angina pectoris, especially the unstable subtype. The underlying mechanism may be attributed to the atherosclerotic lesions stabilization mediated by higher serum IL-1β level. These findings suggested the novel perspective for the complex roles of CHIP in cardiovascular disease.
Abstract 4146134: Assessing the Effectiveness of Ferric Carboxymaltose for Treating Iron Deficiency in Heart Failure Patients Along with its Effect on Clinical Parameters
Authors: Gajbhiye Drumadala , Younus Shifa , Cheema Muhammad Hussnain , Cheema Muhammad Hassan , Fatima Noor , Zafar Aeman , Ali Aamir , Hussain Alamdar , Hussain Tauseef , Choudhary Humais
Published: November 2024

Introduction:
Ferric carboxymaltose (FCM) treatment has been shown to alleviate symptoms and enhance the quality of life in individuals with heart failure characterized by reduced ejection fraction and iron deficiency. Despite prior evidence highlighting its benefits, its impact on clinical parameters remains insufficiently investigated. Our study sought to evaluate the impact of ferric carboxymaltose (FCM) treatment on hospital admissions and mortality rates.

Methods and Materials:
In this prospective, multicenter study, consecutive heart failure patients meeting criteria of a left ventricular ejection fraction of 40% or lower and iron deficiency were enrolled. Participants were allocated into two cohorts, one receiving intravenous ferric carboxymaltose alongside standard heart failure therapy, while the other received a placebo. Ferric carboxymaltose or placebo was administered every 6 months as required, guided by iron indices and hemoglobin levels. The primary endpoint consisted of a hierarchical composite, including death within 12 months post-randomization and heart failure-related hospitalizations within the same timeframe. Significance was determined at a p-value of 0.05.

Results:
Out of the 1500 patients enrolled, 830 were allocated to the ferric carboxymaltose group and 670 to the placebo group. By the end of the 12-month period, 78 patients (9.4%) in the ferric carboxymaltose group and 73 (10.8%) in the placebo group had experienced mortality (P = 0.82). Additionally, there were 102 and 193 hospitalizations for heart failure in the ferric carboxymaltose and placebo groups, respectively, by the end of the 12 months (P = <0.001). The repeated administration of ferric carboxymaltose demonstrated a favorable safety profile with acceptable adverse events observed in most patients.

Conclusion:
Among heart failure patients with reduced left ventricular ejection fraction and iron deficiency, intravenous ferric carboxymaltose was linked to a notable decrease in the likelihood of hospitalizations due to heart failure without any observable impact on mortality rates.
Abstract 4146158: Sodium-glucose cotransporter 2 inhibitors use and outcomes in transthyretin amyloid cardiomyopathy
Authors: Jaiswal Vikash , Hanif Muhammad , Jaiswal Akash , Sundas FNU , Mattumpuram Jishanth , Fonarow Gregg
Published: November 2024

Background:
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated to reduce the risk of hospitalizations from heart failure (HF) and cardiovascular mortality. However, SGLT2i therapy’s potential effects on transthyretin amyloid cardiomyopathy (ATTR-CM) have not been well studied.

Objective:
This study aims to investigate the association of SGLT2-inhibitors with outcomes in patients with transthyretin amyloid cardiomyopathy.

Methods:
The TriNeTX Global Collaborative Network research database was used to identify patients aged ≥18 years of age from January 2000 to April 2023. Patients were categorized into two groups, one with transthyretin amyloid cardiomyopathy on SGLT2i and a control group with transthyretin amyloid cardiomyopathy without SGLT2i. Patients were followed for 1 month and 1 year respectively. Propensity score-matched analysis (PSM) (1:1) was performed on age, gender, race, BMI, hypertension, diabetes mellitus, chronic kidney disease, smoking status, hemoglobin level, low density lipid (LDL) level, left ventricular ejection fraction, pro-BNP levels and various drugs including ACEi, ARBi, beta-blockers, diuretics and statins. Primary outcome was all-cause mortality (ACM), while secondary outcomes were heart failure (HF), ischemic stroke, atrial fibrillation (AF) and ventricular tachycardia (VT).

Results:
After 1:1 propensity score matching, the study cohort comprised 2,153 patients in SGLT2i and 2,153 patients in the control group. The mean age of patients in SGLT2i and control group was 74.2 and 74.4 years. PSM analysis showed that SGLT2-inhibitors in ATTR-CM patients were significantly associated with lower risk of ACM after 1 month (RR, 0.26 (95%CI: 0.18-0.40), P<0.001), and after 1 year (RR, 0.49 (95% CI: 0.41-0.57), P<0.001) compared with a control group. A similar trend was observed with a significant reduction in the risk of ischemic stroke after 1 month (RR 0.321, 95% CI: 0.157-0.660), P<0.001), and after 1 year (RR, 0.572, 95% CI: 0.418-0.782), P=0.001). However, the risk of HF, AF, and VT both at 1 month and 1 year follow-up was comparable between the SGLT2i group and control group among ATTR-CM patients.

Conclusions:
These findings suggest that SGLT2i use among transthyretin amyloid cardiomyopathy patients is associated with reduced risk of mortality and ischemic stroke, but not atrial fibrillation and heart failure.
Abstract 4146163: Statewide Burden of Ischemic Heart Disease Attributable to High Temperature in India and its Burden from 1990-2021: A Benchmarking Systematic Analysis for the Global Burden of Disease Study 2021
Authors: Giri Tapan , gopi Anaswara , Surana Deval , Ahmed Danish , Shandilya Ashwinikumar , Lakkimsetti Mohit , Syed Saif , AMIN VISHRANT , Islam Rabia , Bhalodia Paritaben , PATEL JUHI , DESAI HARDIK , sharma kamal , Thakkar Kshitija Manishbhai
Published: November 2024

Introduction:
Ischemic Heart Disease (IHD) is the primary cause of death and disability among all cardiovascular diseases in India. As global warming escalates, the role of environmental changes, particularly high temperatures, has become a major concern. This study uniquely focuses on high temperatures (HT) as a significant environmental risk factor for IHD, providing the first estimates of its impact over the last three decades in India, including the initial two years of the COVID-19 pandemic.

Method:
Using the global burden of disease 2021 standardized methodology, we estimated deaths, disability-adjusted life years (DALYs), and years of life lost (YLLs) due to IHD attributable to HT in India by age, sex, year and location from 1990-2021. The results were presented in absolute counts and age-standardized rate (per 100,000 person-years).

Results:
From 1990 to 2021, the total number of deaths due to IHD attributable to HT in India rose from 10,874 (95% uncertainty interval: 2,320-19,061) to 40,245 (13,140-68,121). The age-standardized mortality rate (ASMR) saw a total percentage change (TPC) of 42% (19%-178%), and the DALYs rate, (ASDALR) increased by 33% (11%-156%) during this period. Uttar Pradesh recorded the highest total number of deaths at 6,202, followed by Gujarat with 4,821. The highest death counts were in the 70-74 age group, totalling 5,704 (1,888-9,578), and the highest DALYs were in the 55-59 age group at 132,936 (42,040-227,650) in 2021. In terms of gender, males exhibited a consistently higher burden over the last three decades, with a TPC in deaths of 56% for males compared to 30% for females, and DALYs of 44% for males compared to 21% for females.

Conclusion:
In 2021, deaths due to IHD attributable to HT accounted for 2.46% of all CVD-related deaths in India. The rapid urbanization, industrialization, and increasing pollution in India require urgent action from a public health policy perspective. Stakeholders, including government agencies and environmental groups, must collaborate to develop policies that address these issues effectively, aiming to reduce the health impact of environmental risks and enhance cardiovascular health across the nation.
Abstract 4146183: Rheumatoid arthritis is Associated with Sub-Clinical Abnormalities in Myocardial Energetics, Left Ventricular Remodelling, and Increased Fibrosis
Authors: Soo Chin Yit , Jex Nicholas , Duquenne Laurence , Thornton Lucy Elizabeth , Anderton Thomas , Tomoaia Raluca , Lwin May , Kamani Christel , Chowdhary Amrit , Thirunavukarasu Sharmaine , Procter Henry , Kotha Sindhoora , Giannoudi Marilena , Levelt Eylem , Bissell Lesley-Anne , Emery Paul , Saleem Benazir , Wakefield Richard , Mankia Kulveer , Plein Sven
Published: November 2024

Background:
Patients with rheumatoid arthritis (RA) display around 20% increased risk of heart failure, even after adjusting for traditional atherosclerotic risk factors. The reasons behind this are not fully understood. Analogous states of chronic inflammation such as type two diabetes have been shown to be associated with deleterious effects on myocardial metabolism and energetic depletion which predispose to systolic dysfunction. The impact of RA on myocardial energetics and cardiac phenotype in individuals at risk of RA has yet to be established.

Aims:
Using
31
Phosphorous magnetic resonance spectroscopy (
31
P MRS) and cardiovascular magnetic resonance (CMR), we aimed to establish if myocardial energetics, measured as phosphocreatine (PCr) /ATP ratio and quantitative myocardial perfusion were reduced in individuals at risk with isolated anti-CCP positivity (CCP+ve) and those with refractory RA (RRA) compared to healthy volunteers (HV).

Methods:
A total of 30 age and sex matched participants were recruited (11 CCP+ve, 9 RRA and 10 HV). All subjects underwent
31
P MRS and comprehensive CMR protocol including volumetric analysis, quantitative myocardial perfusion and T1 mapping.

Results:
Table-1 shows clinical and CMR /
31
P MRS data.

Groups were matched for age, sex, body mass index (BMI) and systolic blood pressure.

Left ventricular volumes, bi-ventricular systolic function, maximal LV wall thickness and left atrial function were similar between groups. Native T1 values and LV mass were increased in both CCP+ve and RRA versus controls.

PCr/ATP was significantly reduced in both CCP+ve and RRA groups compared to healthy controls.

No significant difference was observed in either stress myocardial blood flow (MBF) or myocardial perfusion reserve (MPR).

Conclusions:
This is the first-time energetic impairment has been reported in both patients with anti-CCP positivity and refractory RA. Our findings also demonstrate increased LV mass and diffuse fibrosis in these groups compared to age, sex and BMI matched controls. These findings may provide a mechanistic insight to the increased incidence of heart failure in individuals with rheumatoid arthritis.
Abstract 4146216: Sex Differences in Cardiogenic Shock: A Meta-Analysis of Outcomes per Etiology (Myocardial Infarction versus Heart Failure)
Authors: Jaimalani Aniket , Venugopal Darshine , Saravanabavanandan Ragavendar , OBI OGECHUKWU , Rasheed Saqlain , Raake Mohammed , Tabassum Maham , Al-Tawil Mohammed , Haneya Assad
Published: November 2024

Background:
Acute myocardial infarction complicated by cardiogenic shock (AMICS) and acute heart failure with cardiogenic shock (AHFCS) are associated with high morbidity and mortality. While women are underrepresented in clinical trials and observational studies of these conditions, emerging evidence suggests potential sex-based differences in presentation, management, and outcomes. Understanding these differences is crucial for tailoring treatment strategies and improving outcomes for both men and women.

Methods:
We conducted a systematic review and meta-analysis of studies reporting sex-specific outcomes in patients with AMICS and AHFCS. A comprehensive search of PubMed, Scopus, and Embase was performed using relevant keywords. 20 Studies reporting outcomes stratified by sex were included. Pooled effect sizes for outcomes were calculated using random-effects models, and heterogeneity was assessed. Subgroup analyses were performed.

Results:
In this study of patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) and acute heart failure with cardiogenic shock (AHFCS), men had a significantly lower risk of mortality compared to women (AMICS: RR 0.82, 95% CI 0.74-0.91; AHFCS: RR 0.84, 95% CI 0.75-0.94). In the AMICS group, men were more likely to undergo revascularization (RR 1.15, 95% CI 1.08-1.23) and receive mechanical circulatory support (RR 1.26, 95% CI 1.19-1.34). However, there was no statistically significant difference in tMCS use between male and female patients with AHFCS (RR 0.98, 95% CI 0.83 - 1.16). Men in the AMICS group also experienced a lower risk of major bleeding (RR 0.78, 95% CI 0.54-1.13) but a slightly higher risk of major adverse cardiovascular events (MACE) (RR 1.04, 95% CI 0.96-1.12).

Conclusion:
Our meta-analysis reveals significant sex-based differences in outcomes and treatment patterns among patients with cardiogenic shock. Men consistently demonstrate a lower in-hospital mortality risk across both AMICS and AHFCS, despite a slightly higher risk of MACE in AMICS. This survival advantage may be partially attributed to increased utilization of revascularization and mechanical circulatory support in men. These findings emphasize the need for further research to elucidate the underlying mechanisms driving these sex-based disparities.
Abstract 4146218: Sex differences in cardiovascular-kidney-metabolic health for degenerative valvular heart disease
Authors: Yang Cheng , Li ziang , Xu Haiyan , Qian Jie , Wu Yong-Jian
Published: November 2024

Background:
Despite the increasing prevalence of degenerative valvular heart disease (VHD), recommended preventive interventions are notably lacking. The cardiovascular-kidney-metabolic (CKM) health approach advocates for multidisciplinary early-stage disease prevention. We aimed to explore sex differences in CKM risk factors associated with VHD.

Methods:
Using data from UK Biobank, participants without a history of VHD or heart failure at baseline were included. We assessed the sex differences in hazard ratios (HRs) and population-attributable risk (PAR) for incident aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR) associated with five CKM risk factors: hypertension, diabetes, obesity, high lipoprotein(a), and chronic kidney disease (CKD).

Results:
Among 463,496 participants (54.4% women), AS, AR, and MR cases were observed at incidence of 1.05 and 0.52, 0.37 and 0.22, 1.04 and 0.70 events per 1000 person-years for men and women, respectively. Hypertension consistently accounted for the largest attributable risk factor for incident VHD in both sexes, with PARs of 29.96% and 26.61% for AS, 23.51% and 16.02% for AR, and 17.56% and 13.09% for MR in women and men, respectively. Compared to men, obesity, CKD, and hypertension were associated with higher risks of AS, AR, and MR in women (women-to-men ratios of HRs: 1.11[1.09–1.36], 1.62[1.01–2.63], and 1.27[1.09–1.49], respectively).

Conclusions:
This study offers comprehensive insights into the profiles of CKM risk factors for degenerative VHD among middle-aged individuals. Tailoring the prioritization of risk factors based on gender has the potential to improve the precision and effectiveness of VHD prevention strategies.
Abstract 4146270: Real-World Performance of the Artificial Intelligence-Enabled Electrocardiogram to Detect Increased Left Ventricular Filling Pressure to Predict Incidence of Heart Failure
Authors: Bhyravajosyula Sri Charan , Medina-Inojosa Jose , Medina-Inojosa Betsy , Lee Eunjung , Mangold Kathryn , Friedman Paul , Attia Zachi , Oh Jae , Lopez-Jimenez Francisco
Published: November 2024

Background:
Our team recently developed an Artificial Intelligence model that enables the identification of increased left ventricular filling pressures using a single-lead electrocardiogram (AI-ECG) with excellent performance (AUC 0.91). However, its ability to predict incident heart failure (HF) in the community is yet to be evaluated.

Hypothesis:
We tested the hypothesis that the output from the AI-ECG will predict the long-term incidence of heart failure (HF) and HF with preserved ejection fraction (HFpEF), and would refine the HF predictive capabilities of the AHA Predicting Risk of Cardiovascular Disease EVENTs (PREVENT
TM
) Equations.

Methods:
Leveraging the resources of the Rochester Epidemiology Project (REP) we analyzed data from patients who sought primary care in Olmsted County, MN, between 1997-2003 with passive follow-up until April 2024. We included those with a digital ECG at baseline and excluded those who were part of the original algorithm development or history of heart failure. The diagnosis of heart failure was ascertained by using ICD codes (ICD9-428,ICD10-I.50) and a word search for the terms related to heart failure. HFpEF was ascertained using the Ejection Fraction (EF) data closest to the heart failure diagnosis date, using EF more than 40% as the criterion. We tested the association between AI-ECG predicted probabilities and new-onset HF and HFpEF using Cox proportional hazard models. These models were also adjusted for cardiovascular risk factors and were stratified to evaluate the effect of the AI-ECG output on PREVENT
TM
-predicted HF at 10 years.

Results:
We included 20,276 subjects, mean age 55±14.03, 52% women, 92% non-Hispanic white. After 18.2±8.5 years of follow-up, 4,008 (19.76%) were diagnosed with HF and 3,812 (18.8%) HFpEF. Risks of HF and HFpEF significantly increased in patients with increased left ventricular filling pressures by AI-ECG, independent of risk factors, all
p
for trend <0.001, see
Fig A-B
, respectively. AI-ECG enhanced the prediction capabilities of the PREVENT
TM
score across all risk groups, see
Fig-C.

Conclusions:
AI-ECG-Derived increased left ventricular filling pressure is associated with new-onset HF and HFpEF in the community and was associated with incidental heart failure at any PREVENT
TM
risk category. Those results suggest a potential role of AI ECG in predicting heart failure.
Abstract 4146321: Mitochondrial Fission Protein 1 (Fis1) Regulates Endothelial Function in Resistance Arterioles in Health and Cardiometabolic Disease
Authors: Wang Jingli , Nolden Kelsey , Egner John , Kakarla Mamatha , Harwig Megan , Roberts Michelle , Arnold Leggy , Hofeld Benjamin , Ying Rong , Wilcox Taylor , Hill R. , Widlansky Michael
Published: November 2024

Background and Research Question:
We have previously shown that mitochondrial fission protein 1 (Fis1) is over-expressed in endothelial cells obtained from humans with diabetes. However, whether Fis1 is mechanistically linked to impaired microvascular endothelial function, either health or cardiometabolic disease, remains unknown.

Methods:
Fresh resistance arterioles from 73 healthy individuals and 24 individuals with type 2 diabetes (T2DM) by gluteal adipose tissue biopsy or discarded surgical tissue. Endothelium-dependent vasoreactivity was tested with increasing doses of acetylcholine (10
-10
to 10
-5
M) following two different molecular manipulations: (1) intraluminal lentiviral transfection for endothelial-specific Fis 1voverexpression vs. control or (2) intraluminal Fis1 siRNA transfection vs. scrambled control. We developed a small peptide Fis1 inhibitor, pep213, and tested if pep213 improved endothelial function in vessels from T2DM patients and healthy individuals exposed to high glucose (HG, 33mM). The impact of molecular manipulations on mitochondrial superoxide (mtO
2
●-
) function were performed using mitoNeoD.

Result:
Fis1 knockdown significantly improved vasodilation to Ach in an endothelial nitric oxide synthase (eNOS)-dependent manner (N=6, P<0.0001) in T2DM vessels and healthy vessels exposed to high glucose (HG=33 mM, N=5, P<0.0001), but had no effect Ach vasodilation in healthy vessels exposed to normal glucose concentrations (NG=90 mg/dL., N=3, P=NS). Fis1 overexpression impaired Ach vasodilation in an eNOS-dependent manner in healthy vessels (N=5, P<0.0001) compared to control transfection. NONOate and papaverine controls for these studies showed effects on smooth muscle reactivity. Intraluminal pep213 (1 µM for 1 hour), reversed impaired eNOS-dependent vasodilation in T2DM vessels (N=5, P<0.001), healthy vessels exposed to HG (N=5, P<0.001), and healthy vessels over-expressing Fis1 (N=5, P<0.05), while a scrambled version of pep213 without ability to bind Fis1 had no effects in any of these scenarios. Pep213 had no effect on vasodilation to NONOate. Pep213 reduced mtO
2
●-
in T2DM and healthy vessels over-expressing Fis1 (N=5, P<0.001).

Conclusion:
Fis1 mechanistically regulates eNOS-dependent vasoreactivity in human vessels, potentially through reducing mtO
2
●-
levels. Fis1 over-expression may be particularly important in T2DM, and pharmacological inhibition of Fis1 can reverse endothelial dysfunction in T2DM human vessels.
Abstract 4146327: MIRACLE2 Score Effectively Stratifies Short-term Prognosis in Patients with Out-of-Hospital Cardiac Arrest Due to Acute Coronary Syndrome
Authors: MIYOSHI KOTARO , Abe Takuro , Kitagawa Kai , Hashimoto Junki , Numaga Miki , Yoneyama Fumika , Ogata Madoka , Kawahara Yuki , Okuda Nozomiko , Tani Akihiro , Ando Toshiyuki , Ishihara Shiro , Komiyama Hidenori , Jujo Kentaro
Published: November 2024

Background:
Despite advances in treatment strategies for out-of-hospital cardiac arrest (OHCA), prognosis remains poor. The MIRACLE2 score is an established risk stratification tool for cardiogenic OHCA, but its utility in acute coronary syndrome (ACS), a leading OHCA etiology, is unclear.

Aims:
To validate the prognostic performance of the MIRACLE2 score in OHCA patients with ACS undergoing urgent/emergent percutaneous coronary intervention (PCI).

Methods:
We conducted a single-center, observational study (COEDO-CPA registry) of consecutive cardiogenic OHCA patients from 2018-2024. Patients with OHCA due to ACS who underwent urgent/emergent PCI were stratified into high-risk (MIRACLE2 score >5), medium-risk (3-4), and low-risk (0-2) groups based on their MIRACLE2 scores. The primary endpoint was 30-day all-cause mortality, compared among risk groups using Kaplan-Meier analysis.

Results:
Of 124 cardiogenic OHCA patients, 80 with ACS-related OHCA undergoing PCI were analyzed (mean age 64.7 years, 89% male). The mean MIRACLE2 score was 3.2, with 18 high-risk, 30 medium-risk, and 32 low-risk patients. Mechanical circulatory support was used in 58%. The high-risk group tended to be older with higher lactate levels, worse renal function, elevated D-dimer, and longer cardiopulmonary resuscitation duration compared to lower-risk groups. Kaplan-Meier analysis demonstrated a graded increase in 30-day mortality across risk groups, with effective risk stratification by the MIRACLE2 score (log-rank p=0.003).

Conclusion:
Among OHCA patients with ACS undergoing PCI, the MIRACLE2 score effectively stratified short-term mortality risk. This validated risk stratification tool could guide treatment strategies and resource allocation in this critically ill population. Incorporating the MIRACLE2 score into OHCA management pathways may optimize care for ACS-related OHCA.
Abstract 4146377: Association of Socioeconomic Disadvantage with Coronary Artery Disease on Coronary CTA and Subsequent Major Adverse Cardiovascular Events: The Mass General Brigham CCTA Registry
Authors: Souza Freire Camila Veronica , Berman Adam , Besser Stephanie , Shiyovich Arthur , Weber Brittany , Cardoso Rhanderson , Biery David , Miao Joanne , Hainer Jon , Gupta Sumit , Aghayev Ayaz , Steigner Michael , McCarthy Cian , Lu Michael , Hedgire Sandeep , DI CARLI MARCELO , Ghoshhajra Brian , Blankstein Ron , Huck Daniel
Published: November 2024

Background:
Socioeconomic disadvantage is associated with worse CV outcomes. However, whether living in a disadvantaged neighborhood is associated with both the presence of coronary plaque identified by Coronary CTA (CCTA) and subsequent MACE is not well defined.

Aims:
To assess whether residence in a disadvantaged neighborhood predicts (1) plaque presence and stenosis severity and (2) long-term MACE after adjusting for plaque burden.

Methods:
We included patients who underwent clinically indicated CCTA from 2006 to 2021. Home addresses were geocoded and mapped to their census block groups. The Area Deprivation Index (ADI) was used to assess neighborhood-level socioeconomic disadvantage from 1 to 10. Based on ADI, patients were grouped into low (1-2), medium (3-5), and high neighborhood deprivation (6-10). The presence of plaque (present vs absent) and severity (no plaque or stenosis [0%], nonobstructive [1-49% stenosis], and obstructive [≥50% stenosis]) were categorized on CCTA. We used logistic regression to assess the association of plaque burden and ADI, and Cox regression to assess the association of ADI and MACE, adjusting for CAD severity and risk factors.

Results:
We included 26,165 patients with a median age of 58 years (IQR 49-67). Of these, 44.5% were female, and 57.8%, 52.8%, and 16.7% had a history of hypertension, dyslipidemia, and diabetes, respectively. The median follow-up after CCTA was 3.9 years (IQR 1.7-7.4). Living in highly disadvantaged neighborhoods was significantly associated with presence of plaque (OR 1.20 [95% CI 1.11-1.30] p<0.001) and obstructive stenosis (OR 1.20 [95% CI 1.11-1.30] p<0.001). Over follow-up, individuals living in medium ADI neighborhoods had a 16% increased hazard of MACE [adjusted HR 1.16 (95% CI 1.02-1.31) p=0.019], and those living in highly disadvantaged neighborhoods had a 20% increased hazard of MACE [adjusted HR 1.20 (95% CI 1.05-1.37) p=0.007] compared to individuals living in the most advantaged neighborhoods.

Conclusion:
Residence in medium and highly disadvantaged neighborhoods was associated with an increased prevalence of plaque and obstructive stenosis on CCTA as well as higher rates of MACE, even after adjusting for traditional CV risk factors.
Abstract 4146462: Ablation versus Anti-arrhythmic Drug Therapy for Ventricular Tachycardia in Patients with Ischemic Heart Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Khan Ubaid , Amin Ahmed Mazen , A. Ibrahim Ahmed , Imran Muhammad , Rakab Mohamed , Iltaf Arej , M. AlBarakat Majd , ranabhat chet , Brilliant Justin , Chaudhry Kashif
Published: November 2024

Background:
Recurrent ventricular tachycardia (VT) is common in patients with ischemic heart disease (IHD), even with anti-arrhythmic drugs on board. While ICDs can abort VT episodes, ICD shocks can be painful. Ablation therapy can reduce the number of ICD shocks and interventions, but the optimal ablation technique is still uncertain.

Purpose:
We aim to review the clinical efficacy and safety of catheter ablation vs anti-arrhythmic drugs in patients with IHD.

Methods:
We conducted comprehensive searches across PubMed, CENTRAL, WOS, Scopus, and EMBASE until Feb 2024. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, along with a 95% confidence interval (CI). This systematic review and meta-analysis was registered with PROSPERO ID: CRD42024551760.

Results:
We included seven RCTs with a total of 836 patients. Patients who underwent ablation had a lower risk of VT storm compared to those who received anti-arrhythmic drugs [RR: 0.65 with 95% CI (0.49, 0.87), P < 0.01), Compared to anti-arrhythmic drugs, the catheter ablation group also required less Appropriate ICD therapy [RR: 0.72 with 95% CI (0.57, 0.90), P < 0.01), and fewer ICD shocks [ RR: 0.64 with 95% CI (0.45, 0.93), P = 0.02). However, there was no significant difference in VT recurrence [RR: 0.91 with 95% CI (0.74, 1.14), P = 0.42), all-cause mortality [RR: 0.87 with 95% CI (0.65, 1.16), P = 0.34), or any adverse events [RR: 0.96 with 95% CI (0.50, 1.84), P = 0.91) between the two groups.

Conclusion:
Our meta-analysis showed that catheter ablation was associated with a reduction in VT storm, ICD therapy, and ICD shocks. However, when compared to anti-arrhythmic drugs, catheter ablation for VT in IHD patients did not appear to afford any significant survival advantage.
Abstract 4146465: Development and Multinational Validation of an Ensemble Deep Learning Algorithm for Detecting Structural Heart Diseases Using Noisy Single-lead Electrocardiograms
Authors: Aminorroaya Arya , Dhingra Lovedeep , Khunte Akshay , Sangha Veer , Pedroso Camargos Aline , Vasisht Shankar Sumukh , Sen Sounok , Haynes Norrisa , Brant Luisa , Barreto Sandhi , Ribeiro Antonio , Krumholz Harlan , Oikonomou Evangelos , Khera Rohan
Published: November 2024

Background:
While portable devices capable of single-lead ECG acquisition have the potential to enhance the scale of structural heart disease (SHD) screening, noise during the acquisition of portable ECGs decreases the performance of deep learning models. Here, we developed and multi-nationally validated a noise-adapted artificial intelligence (AI) model to detect the presence of SHD from single-lead ECGs.

Methods:
We developed ADAPT-HEART (AI Deep learning for Adapting Portable Technology in HEART disease detection) using lead I ECGs paired with echocardiograms within 30 days from 110,228 patients at Yale New Haven Hospital during 2015-2023. We validated the model in five community hospitals and practices in the Northeastern US (N=65,988), and the population-based cohort of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) (N=3,014). SHD was defined by the presence of LVEF <40%, moderate or severe left-sided valvular disease, or severe LVH (IVSd >15 mm + moderate or severe LV diastolic dysfunction). We developed label-specific convolutional neural networks (CNN) using ECG signals augmented with random Gaussian noise to make models resilient to noisy ECG acquisition. The CNN output probabilities and the patient’s age and sex were ensembled using extreme gradient boosting to detect SHD.

Results:
In the development set, 32% had SHD compared with 31-56% across the community hospital sources and 3% in ELSA-Brasil. ADAPT-HEART achieved an AUROC of 0.88 (95% CI, 0.87-0.89) for detecting SHD. With optimized Youden's index, the model has a sensitivity of 86%, specificity of 82%, PPV of 54%, and NPV of 96% for detecting SHD in the held-out test set. The model performed consistently across US data sources (AUROC: 0.81-0.89) and ELSA-Brasil (AUROC: 0.86) with comparable performance across key demographic subgroups. The model showed better discrimination in detecting a composite SHD that encompasses severe valvular disease, rather than moderate or severe valvular disease (AUROC, 0.91).

Conclusion:
ADAPT-HEART, a noise-adapted AI model for 1-lead ECGs, is able to detect a composite of several treatable SHDs with consistent performance across multinational data sources. By integrating outputs from a growing number of wearable/portable devices with ECG capabilities, ADAPT-HEART can enable low-cost, large-scale screening for SHDs in the community.
Abstract 4146587: The Healthy Eating Index as predictor of cardiovascular health among Asian populations in the United States
Authors: Zhou Yu , Gletsu-Miller Nana , Chow Angela , Bidulescu Aurelian , Gonzalez Casanova Ines
Published: November 2024

Introduction/Background:
The Healthy Eating Index (HEI) is an important tool to assess diet quality in the U.S. Asian American populations (AA) have specific dietary patterns. Limited research exists to determine if HEI can adequately predict cardiovascular (CV) health among AA.

Hypothesis:
The HEI is with a better predictor of CV risk among non-Hispanic White persons (NHW) than among AA in the U.S.

Goals/Aims:
To assess if HEI predicts CV risk factors among AA and NHW using the National Health and Nutrition Examination Survey 2017-2020 pre-Pandemic (NHANES).

Methods/Approach:
We used data from 3,770 adults from NHANES 2017-2020 who identified as race/ethnicity AA (877) or NHW (2,893). The HEI-2015 was calculated from 2-day 24-hour recalls. We used multivariate linear and logistic regression models to test associations between HEI and CV risk outcomes. Outcome variables included Body Mass Index (BMI; kg/m
2
), overweight status (BMI ≥ 24 kg/m
2
for AA and BMI ≥ 25 kg/m
2
for NHW), hypertension (SBP≥140 mmHg and DBP≥90 mmHg), and dyslipidemia (blood cholesterol > 200mg/dL, triglycerides > 150mg/dL, LDL-cholesterol > 100 mg/dL and/or HDL-cholesterol < 40 mmol/L). Adjusted models included age, gender, education, marital status, and alcohol intake. P-values < 0.05 were considered significant.

Results/Data:
Asian participants were on average 46.7 (±16.6) years and NHW were 53.7 (±19.9) years. Mean HEI were 58.6 (±14.0) among AA and 51.0 (±13.8) among NHW. Among AA, 61.9% were overweight or obese, and 72.2% among NHW. Approximately 5% had dyslipidemia in both groups. Prevalence of hypertension was 5.0% for AA and 4.0% for NHW. After adjusting for demographic variables, BMI (-0.45, 95% CI -0.62 to -0.29, p<0.001) and overweight status (0.99 95% CI 0.98 to 1.00 vs. normal weight, p=0.01) were significantly associated with HEI scores among NHW, while there were no significant associations among AA.

Conclusion(s):
Significant associations were observed between HEI scores with BMI and overweight status among NHW, but not among AA. A limitation of these analysis is clustering of various ethnic subgroups and national origins under AAs. Additionally, the effect of diet on weight may be less pronounced among AA compared to NHW particularly due to notable differences in waist circumference. Overall, these findings support the need for diet quality assessment tools that better reflect the dietary patterns associated with CV health among AA in the US.
Abstract 4146588: Class 1C Antiarrhythmic Drugs are Safe in Patients with Arrhythmia-induced Cardiomyopathy Following Recovery of Left Ventricular Ejection Fraction
Authors: Pohlkamp Ryan , Chidambaram Vignesh , Kumar Amudha , Ghanta Nikhila , Odueke Adetayo , Vallurupalli Srikanth , Paydak Hakan
Published: November 2024

Background:
Class 1C antiarrhythmic drugs (AADs), such as flecainide and propafenone, are effective first-line agents for rhythm control in atrial tachyarrhythmias. The Cardiac Arrhythmia Suppression Trial (CAST) suggested class 1C AADs increase mortality in patients with myocardial ischemia, limiting their use to those without structural heart disease. Still, the safety and efficacy of class 1C AADs in arrhythmia-induced cardiomyopathy (AiCM) following recovery of LVEF are unexplored.

Goals:
To evaluate the safety and efficacy of class 1C AADs in treating atrial tachyarrhythmias in patients with AiCM following recovery of LVEF compared to patients with no prior cardiomyopathy.

Methods:
We conducted a retrospective cohort study at a single academic center, including adult patients with atrial fibrillation, flutter, or tachycardia and a history of AiCM with recovered LVEF prescribed class 1C AADs since 2010. The control group included patients with atrial tachyarrhythmias prescribed class 1C AADs without prior reduced LVEF. Patients with ischemic or other structural heart diseases were excluded. Primary outcomes were all-cause mortality and sustained ventricular arrhythmias. Secondary outcomes were recurrent atrial tachyarrhythmia, need for electrical cardioversion (ECV) or ablation, and medication discontinuation. Statistical analyses used Cox proportional hazards models.

Results:
Among 356 patients (308 control, 48 AiCM), no significant difference was observed in mortality (7.0% vs. 6.3%, unadjusted HR 0.84, 95% CI 0.25-2.80, p=0.822; adjusted HR (aHR) 0.90, 95% CI 0.15-5.32, p=0.906) or ventricular arrhythmias (3.6% vs. 4.2%, HR 1.14, 95% CI 0.25-5.12, p=0.838; aHR 1.36, 95% CI 0.18-10.50, p=0.767). The recurrence of atrial arrhythmia was similar between the control and AiCM groups (34.4% vs. 41.7%, p=0.328). The need for ECV and ablation, while greater in the AiCM group, was not significantly different between the groups. However, medication discontinuation was significantly higher in the AiCM group (45.8% vs. 29.9%, p=0.027), primarily due to recurrent arrhythmias and medication intolerance.

Conclusions:
Class 1C AADs appear safe in patients with atrial tachyarrhythmias and AiCM following recovery of LVEF, comparable to those without prior cardiomyopathy. However, AiCM patients exhibited higher rates of medication discontinuation, indicating potential challenges in treatment adherence. Further large-scale studies are needed to confirm these findings.
Abstract 4146828: Downregulation of ADAR1 Attenuates Hypothermic Cardioprotection in Aged Donor Hearts During Transplantation
Authors: Cai Dunpeng , Chen Shiyou
Published: November 2024

Heart transplantation remains a vital treatment for end-stage heart failure, yet the scarcity of suitable donor hearts makes the treatment unavailable to many patients in critical need. Aged donor hearts, despite their availability, exhibit increased primary graft dysfunction and decreased survival rates post-transplantation. Addressing this critical barrier could potentially improve post-transplant outcomes and make older donor hearts a viable option. In this study, using a mouse heterotopic heart transplant model, we first confirmed that hypothermic cardioprotection was significantly impaired in aged donor hearts but preserved in young donor hearts. RNA-Seq analyses revealed down-regulation of RNA editing activity along with exacerbated Endoplasmic reticulum stress (ER stress) and increased unfolded protein response (UPR) activity in aged donor hearts post-transplantation. Supplementing cardioplegic solution with rapamycin, an inhibitor of both ER stress and UPR, relieved graft heart dysfunction in aged mice, indicating that ER stress and UPR are responsible for this dysfunction.

Furthermore, we found that Adenosine Deaminase Acting on RNA-1 (ADAR1) was downregulated in aged donor hearts post-transplantation in both our mouse model and in human patients. Importantly, ADAR1 deficiency in young donor hearts abolished hypothermic cardioprotection, leading to increased UPR activity, ER stress, and cellular senescence. Conversely, overexpression of ADAR1 in aged donor hearts by a novel PEG-based nanoparticle delivery in cardioplegic solution enhanced hypothermic cardioprotection by decreasing UPR activity, ER stress, and cellular senescence.

Mechanistically, ADAR1 controls the expression of p16. In aged donor hearts, ADAR1 downregulation caused an increased expression of p16, which competed for its binding with CDK4/6, leading to a decreased phosphorylation of Rb and subsequent cellular senescence.

These findings suggest that ADAR1-associated RNA editing activities play a crucial role in the hypothermic cardioprotection of donor hearts. Supplementing cardioplegic solutions with nanoparticles that enhance ADAR1 activity or modulate ER stress responses may provide a promising therapeutic strategy to improve the viability and/or function of aged donor hearts in transplantation.
Abstract 4146837: Risk of Cardiac Events of New-generation versus Old-generation Bruton Tyrosine Kinase Inhibitors in Patients with Hematological Malignancies: A Systematic Review and Meta-analysis of RCTs
Authors: Aziri Buena , Begic Edin , Herran-Fonseca Catalina , Jekov Laura , Ponte Farias Ana Gabriela , Persaud Carlotta , Gamarra Norma , Vilbert Maysa , Alabbas Fahad
Published: November 2024

Background:
Bruton Tyrosine Kinase inhibitors (BTKi) are targeted therapies that have demonstrated promising results in the treatment of hematological malignancies; however, they are associated with adverse cardiac events. Direct comparisons of the cardiotoxic profile between old-generation and new-generation BTKi are limited.

Research Question:
Are novel BTKi associated with a lower incidence of cardiac adverse events compared with ibrutinib?

Aims:
We aimed to perform a systematic review and meta-analysis of cardiac events from studies comparing new-generation BTKi versus ibrutinib in patients with hematological malignancies.

Methods:
We searched PubMed, Embase, and Cochrane Library for studies comparing any new-generation BTKi with ibrutinib in patients with hematological malignancies. Outcomes included 1) risk of cardiac events; 2) atrial fibrillation (AF); 3) rate of treatment discontinuations due to AF; and 4) hypertension. We pooled risk ratios (RR) with 95% confidence intervals (CI). Statistical analysis was performed using R software 4.3.1, under a random-effects model. Heterogeneity was assessed using I
2
statistics.

Results:
We included four randomized controlled trials with 1905 patients, of whom 957 (50%) received new-generation BTKi. Age ranged from 28 to 90 years, with 1337 (70%) male patients. Prior lines of systemic therapy ranged from none to 12. Overall cardiac events were significantly lower in patients who received novel BTKi compared with those who received ibrutinib (RR 0.75; 95% CI 0.63 to 0.90; p=0.002; I
2
=0%; Fig.1A). New-generation BTKis were associated with a statistically significant reduction in the risk of AF (RR 0.48; 95% 0.35 to 0.64; p<0.001; I2=0% Fig.1B) and treatment discontinuation due to AF (RR 0.07; 95% CI 0.01 to 0.34; p=0.001; I
2
=0%), compared with ibrutinib. However, there was no statistically significant reduction in the risk of hypertension with novel BTKi relative to ibrutinib (RR 0.58; 95% CI 0.34 to 1.01; p=0.053; I
2
=81%).

Conclusion:
Our findings suggest that treatment with new-generation BTKi is associated with a significant reduction in the risk of cardiac events, AF, and AF-related treatment discontinuation compared with the old-generation BTKi.
Abstract 4146967: The Effects of Physical Activity Levels on Body Composition, Exercise Performance, Single Ventricle Function and Self-Perceived Quality of Life in Children and Adolescents with a Fontan Circulation.
Authors: Ng Li Yen , McMahon Colin , James Adam
Published: November 2024

Objectives:
Physically active lifestyles are important for patients with congenital heart disease, including Fontan. This study aims to establish the effect of an active lifestyle in paediatric Fontan patients, determine its relationship with body composition, exercise capacity, ventricle function and quality of life.

Methods:
30 Fontan patients were recruited. Mean age of 14.8±2 years.

Cardiopulmonary exercise tests, bio-impedance analyser, echocardiography and PedsQL questionnaires, generic (V4.0) and cardiac modules (V3.0) were performed. Physical activity level includes structured sports participation, daily stepcounts, and active-zone-minute, AZM (minute spend doing activity ≥ moderate intensity) measured by accelerometer (Fitbit Inspire3).

Patients were considered active if they met 2 of the 3 criteria:

1/ Structured sports training ≥ 2 per week (moderate-vigorous intensity >30 minutes)

2/ Daily steps ≥ 10k

3/ AZM ≥ 60 minutes per day

Results:
60% of patients were considered active, predominantly male, mean age of 14.1 years old. Overall BMI was normal, however 17% (5 of 30) were overweight or obese (Table 1).

The less active Fontan had higher fat% (24.8±8.7 vs 16.6±5.2%; p=0.003), lower percentage appendicular skeletal muscle mass, SMMa%(29.8±3.6 vs 33.7±3.1%; p=0.004), and muscle to fat ratio, MFR (1.4±0.8 vs 2.3±0.9; p=0.015).

The less active group had lower peak oxygen consumption, VO
2peak
(23.5±7.2mL/kg/min vs 35.1±3.96mL/kg/min; p < 0.001), lower peak oxygen pulse (7.9±1.2 vs 10.01±2.9) ml/beat; (p=0.024). No statistical significant differences observed in the ventricle function.

Higher self-report PedQL V4.0 scores noted in the active group, indicated better HRQOL (child’s QOL 88.26±8.6 vs 72.89±17.2%; p=0.003 and parent’s QOL 87.22±10.8 vs 71.6±23.4%; p=0.020).

Higher physical activity level is associated with lower body fat% (r=– 0.521, p=0.003), greater SMMA% (r=0.513, p=0.004), higher peak and submaximal VO2, [VO2/kg peak (r=0.787, p < 0.001) VO2 at ventilatory threshold 1, VT1 (r=0.451, p=0.012)], peak O2pulse (r=0.411, p=0.024), and importantly, higher HRQOL reported [child’s QOL V4.0 (r=0.524,p=0.003), parent’s QOL V4.0 (r=0.423, p=0.020)].

Conclusions:
Higher physical activity levels in paediatric Fontan patients are associated with normal skeletal muscle mass, higher exercise capacity and better HRQOL. Conversely, lower physical activity levels are associated with skeletal muscle mass deficit, increased adiposity and reduced exercise capacity.