bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4121589: Sex differences in Social Determinants of Health and Adverse Outcomes in Atrial Fibrillation: A UK Biobank Study
Authors: Zhou Yusheng , Houle Jonathan , Raparelli Valeria , behlouli hassan , Norris Colleen , Pilote Louise
Published: November 2024

Background:
Beyond the risk of thromboembolic stroke,
people with
atrial fibrillation (AF) are substantially burdened with a higher incidence of cardiovascular mortality, even among patients treated with anticoagulants. The reasons behind these outcomes are only partially understood. Social determinants of health (SDOH), strong independent predictors of major adverse cardiovascular events (MACE) in several cardiac diseases, may play a role; however, their impact on AF prognosis and the differences in SDOH by sex have been insufficiently explored.

Objective:
We investigated the sex differences in the association between SDOH and MACE in patients with AF.

Methods:
Data from the UK Biobank included participants enrolled from 2006 to 2010. An incident AF patient cohort, free of stroke and MI was created. Seventeen SDOH derived from three domains:: socio-economic status, psychosocial factors, and neighborhood/living environment were identified Cox proportional hazards models were used to evaluate the associations of individual SDOH components with the risk of MACE stratified by sex. Covariates including all variables of the CHA
2
DS
2
-VASc Score (Congestive heart failure, Hypertension, Age, Diabetes, prior stroke or transient ischemic attack, Vascular disease and Sex), current use of antiplatelet therapy or anticoagulation, smoking and body mass index. The primary outcome was a composite of MACE (including stroke, transient ischemic attack and arterial thromboembolic event, MI and cardiovascular mortality) and all-cause mortality.

Results:
A total of 23,113 participants with AF (mean age, 62.44 ± 5.88 years; female sex 39.7%) were included. The composite outcome occurred in 5,151 (22%) of participants over 10-year follow up. In the multivariate adjusted model, several SDOH were independently associated with an increased risk of adverse outcomes. Males showed a broader range of SDOH that were significantly associated with outcomes, including unfavourable economic factors and low social support. Despite females had fewer significant SDOH, education-related factors and local crime rates were significant predictors of adverse outcomes (Figure 1).

Conclusions:
Adverse SDOHs are associated with a higher risk of MACE and all-cause mortality in AF, with sex-specific variations. These findings underscore the need of incorporating routinely SDOH assessment into clinical practice to more accurately stratify risk and tailor preventive strategies based on sex-specific data.
Abstract 4121672: Multi-level Factors Mediated the Associations Between Perceived Neighborhood Measures and Type 2 Diabetes: The Midlife in the United States III
Authors: Tamura Kosuke , Moniruzzaman Mohammad , Rogers Breanna , deng Yangyang , Hu Lu , Jagannathan Ram
Published: November 2024

Introduction:
The determinants of type 2 diabetes (T2D) are multifaceted, encompassing individual, psychosocial, health, and neighborhood factors. While these factors have been explored, the mechanisms underlying perceived neighborhood measures and T2D remain understudied. We

aimed

to test whether psychosocial, health, and inflammatory factors mediate the association between perceived neighborhoods and T2D among adults. We

hypothesized

that these factors mediate the relationship between perceived neighborhoods and T2D.

Methods:
Data from the Midlife in the United States 3 (MIDUS3, 2013-2014; MUDIS3 Biomarker Project, 2017-2022) were used (n=564, mean age: 60.7y, female:53.2%, White adults:95.7%). Higher perceived neighborhood scores (social cohesion, safety, quality) represent favorable neighborhoods. T2D (y/n) was defined as either A1c≥6.5%, FGL≥126mg/dL or self-reported T2D. Physical activity (PA), BMI, depression, stress, and CRP were tested as mediators in the cross-sectional association between perceived neighborhood measures and T2D using linear regression (reported odds ratio [OR]) with bootstrap-generated 95% bias-correct confidence intervals (BC CIs) adjusted for covariates (Table).

Results:
Higher neighborhood social cohesion was indirectly related to lower odds of T2D by PA (OR: 0.93 [95%BC CI: 0.86, 0.98]), BMI (OR: 0.90 [0.80, 0.99]), depression (OR: 0.86 [0.75, 0.97]), stress (OR: 0.88 [0.78, 0.97]), and CRP (OR: 0.91 [0.82, 0.98]). Higher neighborhood safety was indirectly related to lower odds of T2D by depression (OR: 0.90 [0.79, 0.98]) and stress (OR: 0.89 [0.77, 0.97]). Higher neighborhood quality was indirectly related to lower odds of T2D by PA (OR: 0.90 [0.82, 0.98]), depression (OR: 0.82 [0.68, 0.96]), stress (OR: 0.83 [0.70, 0.96]), and CRP (OR: 0.88 [0.75, 0.98]).

Conclusions:
Favorable perception of neighborhoods had significant indirect associations with T2D via PA, BMI, depression, stress, and CRP. These mediators could be potential targets for intervention alongside promoting better neighborhoods to improve T2D outcomes. Future studies should replicate this line of research in diverse cohorts to address T2D disparities by socioeconomic status.
Abstract 4121733: Comprehensive Plasma Proteomics Profiling Identifies Circulating Biomarkers to Distinguish Hypertrophic Cardiomyopathy from Other Cardiomyopathies with Left Ventricular Hypertrophy
Authors: Akita Keitaro , Maurer Mathew , Tower Rader Albree , Fifer Michael , Reilly Muredach , Shimada Yuichi
Published: November 2024

Introduction:
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. It is sometimes challenging to distinguish HCM from other cardiomyopathies that cause left ventricular hypertrophy (LVH) such as hypertensive LVH, transthyretin cardiac amyloidosis (ATTR-CA), and aortic stenosis (AS). We aimed to identify a set of plasma protein biomarkers that distinguishes HCM from the other cardiomyopathies with LVH.

Methods:
In this multi-center case-control study, we conducted plasma proteomics profiling of 4,979 proteins in cases with HCM (n=879) and controls with hypertensive LVH (n=331), ATTR-CA (n=169), and AS (n=36). We identified clinical parameters that were significantly (univariable P<0.05) different between HCM and hypertensive LVH. We then specified proteins that were significantly (multivariable P<0.001) upregulated or downregulated in HCM compared to hypertensive LVH by performing multivariable logistic regression analysis on each protein adjusting for the identified clinical parameters (comparison #1). We performed the same analysis between HCM and ATTR-CA (comparison #2) as well as between HCM and AS (comparison #3). We identified proteins that were upregulated in HCM in all 3 comparisons. We also specified proteins downregulated in HCM throughout all 3 comparisons. Finally, using these proteins, we constructed a logistic regression model to distinguish HCM from all 3 control groups combined, and calculated an area under the receiver-operating-characteristics curve (AUROC).

Results:
Eight clinical parameters listed in
Image 1
were significantly different between HCM and the controls and adjusted for in the multivariable logistic regression analyses. In the comparison between HCM and hypertensive LVH, 444 proteins were upregulated and 267 downregulated with multivariable P<0.001 (
Image 1
). There were 226 upregulated and 170 downregulated proteins comparing HCM with ATTR-CA, and 57 upregulated and 74 downregulated proteins when comparing HCM with AS (
Image 1
). Among these proteins, 4 were upregulated in all 3 comparisons with multivariable P<0.001 and 5 were downregulated (
Image 2
). The logistic regression model with these 9 proteins had AUROC of 0.86 (95% confidence interval 0.84-0.88,
Image 3
).

Conclusions:
This study serves as the first to apply comprehensive proteomics profiling to identify circulating biomarkers that distinguish HCM from other cardiomyopathies with LVH independently from potential confounders.
Abstract 4121816: Viral Venture: A Case of Myocarditis and IgA Vasculitis from Adenovirus Infection
Authors: Khalil Ryan , Dahodwalla Mohsin , Barboza Joaquim
Published: November 2024

Case Description:
A 19-year-old man presented to the emergency department for 3 days of shortness of breath, progressive bilateral lower extremity rash, generalized fatigue, and diffuse joint following an earlier visit to urgent care for pharyngitis symptoms. Physical exam was notable for tachycardia, pain with active wrist and ankle range of motion, pharyngeal erythema, cervical adenopathy, and confluent erythematous palpable purpura and petechiae noted on bilateral lower extremities with scattered lesions on his thighs, arms, and back. Laboratory workup notable for markedly elevated high-sensitivity troponin to 3398 ng/L, and elevated CRP. Further workup was notable for normal urinalysis, negative streptococcus antigen, negative ANCA antibodies, ANA, Hepatitis B and C, and cryoglobulins. Imaging and cardiac workup were notable for normal left ventricular function and cardiac MRI notable for late gadolinium enhancement in the anteroapical mid-myocardial region suggestive of myocarditis. Skin biopsy ultimately revealed immunodeposition of IgA on superficial capillaries compatible with a diagnosis of IgA vasculitis. The patient was started on steroids for IgA vasculitis with rapid improvement in his symptoms and he was discharged home in good condition.

Discussion:
Recognizing the severe complications of viral infection can lead to prompt treatment and prevention of progression to severe end organ damage. Our case highlights rarely reported cardiac involvement of IgA vasculitis secondary to adenovirus infection based on laboratory and imaging diagnosis with cardiac MRI. To date, only 16 cases of cardiac involvement in IgA vasculitis have been reported. This case adds to the limited body of published cases describing this presentation of IgA vasculitis and is also consistent with the results of prior cases suggesting that an immunosuppressive regimen including glucocorticoids may help to prevent disease progression and induce remission in cases with cardiac involvement without the need for endomyocardial biopsy.
Abstract 4122035: The Distinct Natural History, Phenotype Spectrum, Familial Penetrance and Clinical Outcomes in Desmin (
DES
)-Associated Cardiomyopathy
Authors: Asatryan Babken , Rieder Marina , Muller Steven , Murray Brittney , Tichnell Crystal , Gasperetti Alessio , Carrick Richard , Te Riele Anneline , Joseph Emily , Zimmerman Stefan , Calkins Hugh , James Cynthia , Barth Andreas
Published: November 2024

Background:
Pathogenic/likely pathogenic variants (P/LP) in the desmin (
DES
) gene cause heterogeneous cardiomyopathy and skeletal myopathy phenotypes.

Research Questions:
Limited data suggest that patients with P/LP
DES
variants have a high incidence of major adverse cardiac events (MACEs), including cardiac conduction disease requiring pacemaker implantation (CCD-PM), sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, heart transplant, HF-related death). However, small cohort sizes have limited full clinical characterization.

Aims:
We aimed to describe the natural history, phenotype spectrum, familial penetrance and MACE in patients with P/LP
DES
variants identified via clinical genetic testing.

Methods:
We conducted a systematic review and individual patient data meta-analysis of cardiac and skeletal myopathy phenotypes and MACE (CCD-PM, VA and HF events) in patients with P/LP
DES
variants by retrieving publications from Medline (PubMed) and Embase. Diagnosis of cardiomyopathy or MACE were both considered evidence of cardiac involvement.

Results:
Out of 4,212 screened records, 72 met inclusion criteria. In total, 230 patients were included (52.6% male, 52.2% probands, median age: 31 years at first evaluation [22.0; 42.8]). Eighty-five (37.0%) patients showed isolated cardiac involvement, 89 (38.7%) cardiac and skeletal muscle involvement, 39 (17.0%) only skeletal muscle involvement, and 17 (7.4%) had neither phenotype. Overall, 130 (56.5%) patients were diagnosed with a cardiomyopathy and 134 (57.4%) patients developed MACE (96 [41.7%] had CCD-PM, 36 [15.7%] sustained VA, and 43 [18.7%] HF events). Familial cardiac disease penetrance was 69.1% (76/110) in relatives with P/LP
DES
variants. Out of 40 patients who presented with isolated CCD-PM phenotype, 18 (45.0%) were diagnosed with a cardiomyopathy after 6 [2.0; 16.0] years of follow-up. In multivariable analysis, male sex and non-missense variants were associated with higher risk of sustained VA (HR 2.71, p=0.008, and HR 4.62, p<0.001, respectively) and HF events (HR 2.63, p=0.005, and HR 2.79, p=0.015).

Conclusions:
DES
cardiomyopathy demonstrates a distinct natural history, characterized by high familial penetrance and a high MACE burden. Male patients and those carrying non-missense variants are at higher risk for sustained VA events and may benefit from primary preventive ICD implantation even in the absence of severe LV systolic dysfunction.
Abstract 4122257: Inhibition of Neutrophil Extracellular Traps Prevents Heart Failure by Preserving Mitochondrial Function of Cardiomyocytes in Mice
Authors: Ichimura Shohei , Misaka Tomofumi , Ogawara Ryo , Nishiura Kazuto , Sato Yu , Miura Shunsuke , Yokokawa Tetsuro , Sato Takamasa , Oikawa Masayoshi , Kobayashi Atsushi , Yoshihisa Akiomi , Ishida Takafumi , Takeishi Yasuchika
Published: November 2024

Background:
We have previously demonstrated that neutrophil extracellular traps (NETs) in myocardial tissue are associated with cardiac dysfunction and adverse outcomes in patients with heart failure with reduced ejection fraction. Here, we aimed to elucidate the underlying mechanisms and to clarify whether inhibiting NETs could rescue the cardiac phenotype using
ex vivo
and
in vivo
models.

Methods and Results:
Given that peptidyl arginine deiminase 4 (PAD4) is essential for the formation of NETs, PAD4 knockout mice were used for this study. First, we assessed the mitochondrial function of cardiomyocytes by conducting real-time measurements of the oxygen consumption rate in
ex vivo
. Extracellular flux analysis revealed that NETs-containing conditioned medium from wild-type neutrophils or purified NET components led to impaired mitochondrial oxygen consumption of adult mouse cardiomyocytes, while these effects were abolished when PAD4 in neutrophils was genetically ablated (Figure 1). In a murine model of pressure overload-induced heart failure, transverse aortic constriction (TAC) operation was performed on wild-type and PAD4 knockout mice. Immunohistological analysis demonstrated that TAC induced the formation of NETs in the myocardium, with the greatest number of NETs occurring at 1 day, persisting into the failing stage at 4 weeks in wild-type mice, while PAD4-deficient hearts displayed no presence of NETs in the heart tissue (Figure 2). Four weeks after TAC, left ventricular ejection fraction was reduced in wild-type mice, whereas PAD4 knockout mice displayed preserved left ventricular ejection fraction (Figure 2). Finally, we investigated the bioenergetics of cardiomyocytes isolated from PAD4 knockout mice after TAC. Maximal mitochondrial oxygen consumption rate in cardiomyocytes isolated from TAC-operated PAD4 knockout mice was significantly higher than in those from TAC-operated wild-type mice (Figure 3).

Conclusion:
Our data suggest that NETs directly derived impairment of mitochondrial function in cardiomyocytes. Inhibiting NETs represents a potential therapeutic approach for heart failure, preventing mitochondrial dysfunction of cardiomyocytes.
Abstract 4122486: Multicenter Study of Primary Fetal Cardiomyopathy: Clinical Outcomes And Genetic Etiologies, A Fetal Heart Society Research Collaborative Study
Authors: Burande Astha , Hornberger Lisa , Caluseriu Oana , Peyvandi Shabnam , Bolin Elijah , Cavalle-Garrido Tiscar , Chandra Sue , Cnota James , Conway Jennifer , Creighton Sara , Cuneo Bettina , Despres Marlayna , Doan Tam , Doucet J. Scott , Grenier Michelle , Hogan Whitnee , Kaplinski Michelle , Bijji Mahima K , Kavanaugh-Mchugh Ann , Keller Sam , Kwon Elena , Lipshultz Steven , Majeed Amara , Mansukhani Gitanjali , McIntosh Amanda , McVadon Deani , Michelfelder Erik , Miller Michelle , Milligan Caitlin , Mital Seema , Montes Gil Adriana , Moon-Grady Anita , Mulla Neda , patel sheetal , Pruitt Cathleen , Qasim Amna , Rajagopal Hari , Ro Sanghee , Schidlow David , Schneider Kristin , Srinivasan Ranjini , Sutton Jennifer , taylor carolyn , McBrien Angela
Published: November 2024

Background:
Fetal cardiomyopathy (FCM) affects 8 per 100,000 live births, often with unknown etiology. Progress in fetal cardiac screening, genetic testing and management may have impacted historically poor outcomes.

Aims:
We sought to investigate genetic associations and clinical outcomes of FCM in the current era.

Methods:
This was a retrospective Fetal Heart Society Research Collaborative cohort study of FCM cases diagnosed from January 2017-December 2021 in 39 centers. Cases of fetal myocardial disease attributable to maternal diabetes, structural heart disease, arrhythmia or extra-cardiac conditions were excluded. Data including outcomes to 1 year after birth were collected. Significance of genetic testing results and FCM subtype were classified by each center.

Results:
There were 138 FCM cases diagnosed at a median gestational age of 27
+4
weeks (range 13-39 weeks). Suspected fetal heart disease (41%, 56/138) was the most common referral indication. There was a known family history of CM in 19% (26/138). FCM phenotypes included 38% (52/138) dilated, 24% (33/138) hypertrophic, 17% (24/138) non-compacted, 10% (14/138) mixed, 5% (7/138) restrictive, 3% (4/138) ventricular aneurysm, 3% (4/138) unspecified. Hydrops was present at diagnosis in 15% (20/138) and by delivery or at fetal demise in 26% (36/138). Of 128 continued pregnancies, 7% (9/128) had a fetal demise, 92% (118/128) a live birth and one was lost to follow-up. Among live births, 10% (12/118) received only palliative care. Of 106 actively treated, 75% (80/106) survived to 1 year; 7% (7/106) required ECMO, and 22% (23/106) were listed for transplant with 18 of these successfully transplanted. Of the cohort, a total of 80% (110/138) had genetic testing (including 30 with invasive prenatal testing), with 38% (52/138) having a confirmed genetic etiology and 28% (38/138) with a variant of uncertain significance (VUS) (Figure 1). Transplant-free survival to 1 year was similar for those with and without a genetic diagnosis (40%,21/52 vs 47%,40/86, p=0.48).

Conclusion:
Outcomes remain poor in FCM, with <50% 1-year survival overall. Confirmed genetic etiologies are now identified in nearly 40%, highlighting the importance of genetic testing.
Abstract 4122590: Sex Differences in the Prescription of P2Y12 Inhibitor Agents Following Percutaneous Coronary Intervention
Authors: Laband William , Sedrakyan Surik , Khan M Faisal
Published: November 2024

Background:
There remain significant gender inequalities in the delivery of healthcare. Third generation P2Y12 inhibitors (P2Y12i), Prasugrel and Ticagrelor, are the standard of care for dual antiplatelet therapy (DAPT), especially in the setting of acute coronary syndrome (ACS). We hypothesized that women are less likely to be prescribed 3
rd
generation P2Y12i than clopidogrel, due to concealed gender inequalities.

Methods:
We examined gender differences in post percutaneous coronary intervention (PCI) care in a cohort of 12,354 PCI cases from all 14 hospitals within the Steward Health Care system in the United States of America (USA). After removal of duplicates, 10,415 patients were included in the final analysis, with 7,191 males (69.04%) and 3,224 (30.96%) females. We conducted statistical analyses using the Chi-Square test of independence to explore associations between categorical variables, and logistic regression analysis to model the probability of clopidogrel prescription based on patient characteristics, adjusting for confounders.

Results:
We found that women were less likely than men to be prescribed 3
rd
generation P2Y12i compared to clopidogrel with an odds ratio (OR) of 0.74 (CI 0.69-0.80, p<0.001). We adjusted for the following variables: age, weight, insurance type, number of stents, and relevant co-morbidities. The association remained significant with an OR of 0.83 (CI 0.76-0.90, p<0.001). In a subgroup of ACS patients, the association was also statistically significant with an OR of 0.77 (CI 0.67-0.88, p<0.001).

Conclusions:
Our study reveals that significant gender disparities exist in the prescription of P2Y12i after PCI, with women having a greater likelihood of being prescribed clopidogrel compared to more effective and guideline directed, 3
rd
generation agents. This association held true after accounting for confounding variables including older age and an increased prevalence of co-morbidities in the female group. Our conclusions are likely to have been influenced by unmeasured socioeconomic factors, such as household income and medication costs. Therefore, further research ought to be conducted to better understand the reasons behind the association observed.
Abstract 4122620: Triglyceride Levels Associate With Cardiovascular Risk Across the Full Range but Not Among Individuals With Mild-to-Moderate Hypertriglyceridemia
Authors: Nordestgaard Ask , Pradhan Aruna , Everett Brendan , MacFadyen Jean , Bhatt Deepak , Visseren Frank , Libby Peter , Santos Raul , Nissen Steven , Nordestgaard Borge , Ridker Paul
Published: November 2024

Background:
Guidelines focus on individuals with triglyceride levels of 200 to 499 mg/dL (2.3 and 5.6 mmol/L), a group for whom triglyceride-lowering therapy does not convincingly decrease risk.

Hypotheses and goals:
We re-assessed the hypotheses that triglyceride levels across the full biological range and within this constrained range strongly associate with cardiovascular risk.

Methods:
We calculated multivariable adjusted hazard ratios for major cardiovascular events and death according to baseline triglyceride levels among 119,573 individuals with triglycerides across the full biological range from the Copenhagen General Population Study, among 27,757 individuals with baseline triglycerides between 200 and 499 mg/dL (2.3 and 5.6 mmol/L) from the Copenhagen General Population Study and the Women’s Health Study, and among 31,372 individuals with mild-to-moderate hypertriglyceridemia participating in the PROMINENT, REDUCE-IT, and STRENGTH randomized trials.

Results:
Increasing triglyceride levels across the full range were associated with increasing risk of major cardiovascular events (N=12,241) (Figure 1). In individuals with mild-to-moderate hypertriglyceridemia from the two cohorts, combined hazard ratios (95% confidence interval) for major cardiovascular events (N=3,928) from lowest to highest triglyceride quartile were 1.0 (referent), 0.95 (0.87-1.04), 1.04 (0.95-1.13), and 1.13 (1.04-1.23). In the contemporary trials of patients selected for mild-to-moderate hypertriglyceridemia, the corresponding hazard ratios for major cardiovascular events (N=4,265) from lowest to highest triglyceride quartile were 1.0 (referent), 1.01 (0.93-1.10), 1.05 (0.96-1.14), and 1.10 (1.01-1.19). In neither prospective cohorts nor trials were triglyceride levels strongly associated with risk of cardiovascular or all-cause death within the constrained range.

Conclusions:
Contrary to expectations, individuals with mild-to-moderate hypertriglyceridemia may not express the same magnitude of cardiovascular risk as that observed across the full range of plasma triglycerides. Future trials of triglyceride-lowering therapy may want to consider enrollment across a wider range of triglyceride levels if there is no prior history of pancreatitis.
Abstract 4122710: Impact of cigarette smoking on long-term clinical outcomes in patients with coronary chronic total occlusion lesions
Authors: AHN JIHUN , Bae Minook
Published: November 2024

Cigarette smoking is a significant risk factor for coronary artery disease (CAD). However, evidence regarding on the long-term clinical effects of smoking in the Asian population with chronic total coronary occlusion (CTO) is insufficient. This study aimed to assess the effects of smoking on 5-year (median follow-up period 4.2 ± 1.5 years, interquartile range 4.06-5.0 years) clinical outcomes in patients with CTO lesions who had undergone percutaneous coronary intervention (PCI) or medical treatment (MT). We enrolled 681 consecutive patients with CTO who had undergone diagnostic coronary angiography and subsequent PCI or MT. Patients were categorized into smokers (n = 304) and non-smokers (n = 377). The primary endpoint encompassed major adverse cardiovascular events (MACE), including a composite of all-cause death, myocardial infarction (MI), and revascularization over a 5-year period. Propensity score matching (PSM) analysis was used to adjust for potential baseline confounders. After PSM analysis, two propensity-matched groups (200 pairs, n = 400) were generated, and the baseline characteristics of both groups were balanced. The smokers exhibited a higher cardiovascular risk of MACE (29.5% vs. 18.5%,
p
= 0.010) and non-target vessel revascularization (17.5 vs. 10.5%,
p
= 0.044) than those of the non-smokers(Table 1). In a landmark analysis using Kaplan-Meier (KM) curvesat the 1-year, the smokers had significantly higher rate of MACE in early period (up to 1-year) (18.8% and 9.2%, p=0.008) compared with non-smokers(Figure 1). Cox hazard regression analysis by propensity score-adjustedwith , revealed that smoking was independently associated with an increased risk of MACE. The findings indicate that smoking is a strong cardiovascular risk factor in patients with CTO, regardless of treatment strategies (PCI or MT) (Figure 2). In addition, in a subgroup analysis, the risk of MACE was most prominently elevated in the group of smokers who underwent PCI.
Abstract 4122763: Health Status Outcomes of Antianginal Therapies in Patients After Coronary Revascularization: Insights From the GREAT Disease Registry Study
Authors: zhao xiliang , Zeng Yong
Published: November 2024

Background:
The impact of antianginal therapies on the health status of coronary artery disease (CAD) patients who have undergone coronary revascularization has not been extensively researched. This study aimed to investigate the effect of nicorandil on the health status in patients after coronary revascularization, measured by the Seattle Angina Questionnaire (SAQ).

Methods:
We analyzed data from 1,556 patients enrolled in the GREAT Disease Registry Study (Clinicaltrial No. NCT05050773) between September 2021 and May 2022. Changes in SAQ summary score (SAQ-SS) from baseline to 3, 6, 9, and 12 months were assessed. Statistical methods included a linear mixed-effects model and propensity score matching (PSM) for comparative analysis.

Results:
Among the 1,038 patients receiving revascularization analyzed (22.7% female; mean age [SD], 59.9 [10.2] years), 648 (62.4%) received nicorandil, while 390 (37.6%) did not. In the linear mixed-effects model analysis, statistically significant improvements were observed with nicorandil in SAQ-SS across all time points (
Table 1
), indicating beneficial effects of nicorandil on health status outcomes after revascularization. Sensitive analysis was conducted using the PSM method. After PSM adjustment, both groups comprised 321 patients each. The change in SAQ-SS from baseline to 12 months was significantly greater in the nicorandil group (19.2 ± 14.06 points) compared to the non-nicorandil group (14.91 ± 12.9 points, p < 0.001).

Conclusions:
These findings indicated that nicorandil is associated with improved health status outcomes in CAD patients who have undergone coronary revascularization.
Abstract 4123480: Navigating Aspirin Allergy With Rapid Desensitization In A Patient Requiring Urgent Coronary Intervention
Authors: Daghstani Omar , Derakhshesh Matthew , Ghazal Mohamad , Lyubarova Radmila
Published: November 2024

Introduction:
Aspirin (ASA) hypersensitivity is a challenge in determining the appropriate, cost-effective therapy in patients after percutaneous coronary intervention (PCI). Various ASA desensitization protocols were studied and showed favorable outcomes. In this case, we highlight the use of rapid ASA desensitization protocols for patients requiring dual antiplatelet therapy (DAPT) post urgent PCI.

Case:
A 52-year-old male presented with severe left-sided chest pain associated with diaphoresis. He had a history of allergic reaction to ASA at the age of 18 years with swelling of the face and throat without shortness of breath or hypotension. Physical examination was unremarkable except for tachycardia. Workup showed no ECG abnormalities but significantly elevated, uptrending high sensitivity troponin. Medical management included clopidogrel load, heparin drip, and nitropaste for persistent pain. Urgent coronary angiography showed a severe bifurcating lesion in the LCx and OM1 arteries, successfully treated with the T stent technique using a drug-eluting stent. He received cilostazol and prasugrel, overlapped with a tirofiban drip post PCI. ASA desensitization was performed with oral ASA every 90 minutes for four doses (Figure). Vital signs were monitored every 30, 60, and 90 minutes after each dose. He was discharged home with no reported symptoms on follow up.

Discussion:
DAPT with ASA and oral P2Y12 inhibitors is recommended for patients with PCI. ASA desensitization could be considered for patients who are intolerant to ASA. Major clinical ASA desensitization protocols, like in ADAPTED and SCRIPPS studies, showed good outcomes in major adverse cardiovascular events. However, one limitation of these widely used protocols is the prolonged time required to achieve desensitization. The rapid protocol used in our patient who did not have ASA exacerbated respiratory disease showed effectiveness with shorter hospital stay.

Conclusion:
ASA desensitization is an appropriate option for patients with a history of ASA allergy requiring DAPT. Rapid desensitization protocols are associated with shorter hospitalization courses, and future efforts should evaluate their effectiveness in randomized controlled trials.
Abstract 4124182: Depression Symptomatology as Predictor of Incident Major Vascular Outcomes: Results from the Hispanic Community Health Study/Study of Latinos
Authors: Trifan Gabriela , Gallo Linda , lamar melissa , Wassertheil-Smoller Sylvia , Gonzalez Hector , Perreira Krista , Cai Jianwen , Rundek Tatjana , Levin Bonnie , Daviglus Martha , Pirzada Amber , Testai Fernando
Published: November 2024

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<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 <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 <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 4124354: Transplantation of vascularized cardiac microtissue derived from human iPS cells improves impaired electrical conduction capacity in a porcine myocardial injury model
Authors: Kuroda Yuki , Iida Jun , Murata Kozue , Kobiki Jumpei , Minatoya Kenji , Masumoto Hidetoshi
Published: November 2024

Background:
To realize efficient regenerative medicine using human iPS cell (hiPSC)-derived cardiac tissue, it is necessary to achieve electrical synchronization between the graft and the host heart and to improve conduction disturbances in the impaired heart. In this study, we aimed to demonstrate that the transplantation of hiPSC-derived vascularized cardiac tissue can improve these conduction disturbances using a porcine myocardial injury model.

Methods:
We prepared cell sheet-shaped vascularized cardiac microtissue (VCM) by seeding cardiomyocytes, endothelial cells, and vascular mural cells differentiated from hiPSCs onto temperature-responsive culture plates and thickening them using dynamic rocking culture. We induced myocardial injury (MI) via epicardial cryoablation in immunosuppressed crown minipigs and transplanted the VCMs immediately after MI induction, covering the cryoinjury-induced MI area. The pigs underwent epicardial electroanatomic mapping under sinus rhythm and epicardial pacing, both immediately before and one week after MI induction, while using amiodarone. Differences in myocardial voltages and conduction velocities were assessed between VCM and sham groups (N=3 in each group). After electroanatomic analysis, the hearts were harvested and subjected to histological examination.

Results:
One week after MI induction, mean voltages at the MI site decreased in both groups during sinus rhythm, remote site pacing, and combined remote and MI site pacing (11.05 to 1.74 mV, 14.26 to 3.44 mV, and 15.61 to 3.67 mV, respectively, in the VCM group; and 8.72 to 2.70 mV, 19.64 to 3.64 mV, and 14.66 to 1.96 mV, respectively, in the Sham group). Mean voltages at the remote site also decreased in both groups during the same conditions (12.57 to 4.53 mV, 10.61 to 3.38 mV, and 19.56 to 5.85 mV, respectively, in the VCM group; and 8.75 to 6.03 mV, 14.15 to 5.79 mV, and 13.67 to 6.23 mV, respectively, in the Sham group). The mean conduction velocity between the remote and MI sites was numerically higher in the VCM group compared to the Sham group (2.84 m/s vs. 1.74 m/s, respectively). Histological examination confirmed that in the VCM transplantation group, the VCM remained intact, completely covering the MI area.

Conclusions:
The transplantation of VCM showed a tendency to improve conduction disturbances in the porcine MI model. This suggests that the graft may synchronize with the host and function mechanically after cell transplantation.
Abstract 4124828: The Methylation Landscape Of Human Aortic And Mitral Valvular Interstitial Cells
Authors: Halawa Sarah , Latif Najma , Tseng Yuan-Tsan , Moustafa Ahmed , Aguib Yasmine , Yacoub Magdi
Published: November 2024

Valvular interstitial cells (VICs), the valves’ predominant cell type, are crucial in ensuring proper valve function, structural integrity, tissue repair and valve homeostasis. DNA methylation regulates gene expression profiles and a matched aortic to mitral human VIC methylation analysis will further our understanding of aortic- and mitral-specific VIC biology and pathobiology. This is the first study analyzing methylation profiles of non-diseased, matched human aortic and mitral VICs. We analyzed the differential methylation fingerprint of 12 non-diseased aortic and mitral VICs (10 males:2 females; 42–64 years) extracted from de-endothelialized leaflets using reduced representation bisulfite sequencing (RRBS) on HiSeq2500. Analysis of methylation levels of 12,676 genome-wide promoters revealed 651 differentially methylated (DM) promoters. The top 3 DM promoters were linked to
TBX4
(meth diff = -28.9%, P = 5.2E-135) essential for valve morphogenesis, to
EXOC3L2
(meth diff = 25.7%, P = 1.3E-92) and
NT5DC2
(meth diff = -20.3%, P = 7.1E-69) potentially implicated in ECM remodeling, the former via vesicle trafficking and the latter through nucleotide metabolism. Functional classification and network analysis showed that the genes associated with the DM promoters were enriched for WNT-, TGFβ-, FGF-, EGF- and PDGF- pathways involved in physiological processes such as valve development, repair and VIC regulation, as well as pathological processes such as calcification. Additional enrichment was detected for integrin- and cadherin- pathways involved in cell-cell-ECM interactions and endothelin- and VEGF pathways involved in hemodynamic regulation. This work provides the first insight into the differential methylation regulation patterns of human aortic and mitral VICs. Understanding how aortic and mitral VICs are differentially epigenetically regulated will extend our understanding of their role in aortic- and mitral-specific leaflet homeostasis, susceptibility to disease processes and will contribute to dynamic innovative experimental setup designs, animal-free human-based modeling frameworks, tissue engineering and drug identification approaches.
Abstract 4124875: Association between Elevated Lipoprotein(a) and Cardiovascular Events and Mortality in a Nationally Representative Sample of US Medicare, Medicaid, and Commercial Enrollees with ASCVD
Authors: Hu Xingdi , Lozama Tony , Petrilla Allison , Agatep Barnabie , McMorrow Donna , Mohammadi Iman , Reisman Lonny , Wong Nathan
Published: November 2024

Background:
Elevated lipoprotein(a) [Lp(a)] is an independent and causal risk driver for atherosclerotic cardiovascular disease (ASCVD). Few patients with ASCVD receive Lp(a) screening and real-world data assessing the association between elevated Lp(a) and risk of cardiovascular (CV) events and mortality is limited.

Objectives:
To examine the association of elevated Lp(a) and risk of CV events and death in an ASCVD population using large US health claims databases.

Methods:
Patients with ASCVD were pooled from US Medicare, commercial, and Medicaid health plans from 2017 to 2022. Lp(a) levels were linked at the patient level from HealthVerity Lab Data and categorized as: <30 mg/dL (<75 nmol/L), ≥30-<50 mg/dL (
>
75-<125 nmol/L), ≥50-<70 mg/dL (
>
125-<175 nmol/L), ≥70-<90 mg/dL (≥175-<225 nmol/L) and ≥90 mg/dL (≥225 nmol/L). Patients were followed from the 1
st
ASCVD diagnosis (index) to insurance plan disenrollment, death, or end of study. Cox regression, adjusted for age, sex, race, insurance, comorbidities, LDL-C, and other risk factors, measured the association between Lp(a) levels and risk of CV events and death.

Results:
Of 28.8 million ASCVD patients, 180,240 (0.6%) had Lp(a) levels: mean(±SD) age 68.6±1 years, 50.1% male, 5.9% Black, 2.8% Hispanic, 2.1% Asian, 72.8% Medicare, 21.8% commercial, and 5.4% Medicaid. Mean follow-up was 3.7 years; 23.3% and 15.7% had Lp(a) ≥50mg/dL [≥125 nmol/L] and ≥70 mg/dL (≥175 nmol/L), respectively. Black patients had highest median Lp(a) (50 mg/dL/111 nmol/L), followed by Asian (13.5 mg/dL/35.5 nmol/L), White (13 mg/dL/32 nmol/L), and Hispanic (11.5 mg/dL/29 nmol/L) patients. Lp(a) levels of ≥30-<50 mg/dL, ≥50-<70 mg/dL, ≥70-<90 mg/dL, and ≥90 mg/dL were associated with 7%, 10%, 16%, and 26% greater risks of CV events vs. <30 mg/dL (p-values <0.0001; cumulative incidence reported in Figure 1). All-cause mortality risk was also greater for those with Lp(a) ≥90 mg/dL vs. <30 mg/dL: hazard ratio (HR)=1.11, p=0.003. Similar trends persisted for patients with LDL-C ≤70 mg/dL.

Conclusion:
In this national-scale real-world cohort of patients with ASCVD, Lp(a) testing is infrequent and elevated Lp(a) levels were significantly associated with a greater risk of CV events and mortality.
Abstract 4125294: Fontan-Related Lymphatic Complications are Associated with Extracardiac Outcomes and Morbidity
Authors: Boyd Riley , Laternser Christina , Patel Shivani , Migally Karl , patel sheetal
Published: November 2024

Background:
Patients born with single ventricle anatomy palliated with the Fontan procedure are at risk of lymphatic complications (LC), including plastic bronchitis, protein losing enteropathy, ascites, and hypoalbuminemia. The mechanism of LC, associated risk factors, and impact on outcomes are not well understood.

Aim:
We aimed to describe the prevalence of Fontan-related LC, expand on their association with previously reported risk factors, and explore the impact on mortality and transplantation.

Methods:
We performed a single-center, retrospective, cross-sectional cohort study of patients with Fontan circulation seen between 2009-2022, including those with cardiac catheterization and echocardiography within six months. Univariate comparisons were completed comparing those with and without LC.

Results:
A total of 144 Fontan patients were included with mean age of 23.6±11.9 years, with average of 18.8±10.5 years after their Fontan. Of those, 68 patients (48.6%) had at least one LC. There was no difference in demographic or anthropometric data in those with versus without LC, however patients with LC had their Fontan at an older age (5.6 vs 3.8 years,
p
=0.001). The presence of LC was associated with higher likelihood of thromboembolism (25% vs 7.9%,
p
=0.005), arrhythmia (45.6% vs 21.1%,
p
=0.002), lower estimated glomerular filtration rate (102.0±25.5 vs 111.6±17.9,
p
=0.02) and higher Fontan mean pressures noted on catheterization (14.8±3.8 vs 12.1±3.8 mmHg,
p
<0.001). Notably, LC were not related to the presence of moderate to severe ventricular dysfunction or moderate to severe atrioventricular valve regurgitation. Fontan patients with LC had higher rates of transplantation (25.4% vs 4%,
p
<0.001) and mortality (18% vs 4%,
p
=0.006).

Conclusions:
Fontan-related LC are associated with extra-cardiac morbidities and greater transplant and mortality rates. Our study suggests that LC are associated with venous congestion and not necessarily dependent on cardiac function.
Abstract 4125497: Diagnostic Discrepancies Revealed by Explant Pathology at the Time of Cardiac Transplant in Patients Clinically Diagnosed with Nonischemic Cardiomyopathy: Role of Cardiac Magnetic Resonance Imaging
Authors: Austin Brett , Ahmed Enas , Bois Melanie , Bois John , Redfield Margaret , Rosenbaum Andrew
Published: November 2024

Background:
Differentiating between causes of non-ischemic cardiomyopathy is important for disease-directed treatment. Cardiac MRI (CMR) and the use of late gadolinium enhancement (LGE) have proven useful for enhancing diagnostic accuracy. Definitive assessment of cardiomyopathy etiology by explant pathology facilitates direct evaluation of CMR utility.

Hypothesis:
We hypothesized direct comparison between pre-transplant (Tx) CMR and explant pathology will improve the characterization of undifferentiated cardiomyopathy through examination of cases where pre- and post-Tx diagnoses were discordant.

Aims:
To evaluate discrepant cases to describe imaging patterns in relation to post-Tx diagnosis.

Methods:
Institutional Tx recipients between 2000 and June 2023 were queried for pre-Tx MRI (n=122). Discrepant cases were identified (n=8). Pre-Tx diagnostic modalities, including CMR, were reviewed, and CMR patterns were evaluated in association with ultimate explant diagnosis.

Results:
Of the eight patients with discrepant diagnoses, five carried clinical diagnosis of dilated cardiomyopathy, one hypertrophic cardiomyopathy, one peripartum cardiomyopathy, and one congenital heart disease having undergone tricuspid valve and ASD repair. Pathologic evaluation most frequently identified biventricular or left ventricular arrhythmogenic cardiomyopathy (ARVC) (n=6), where CMR disclosed a diffuse pattern of subepicardial LGE and pre-Tx diagnosis of DCM was most common. Two of these pathologic descriptions represented a different disease on genetic evaluation: one patient had Danon disease, another had a LMNA pathogenic variant. The presumed peripartum cardiomyopathy was identified as Fabry’s disease on pathology (however, genetic testing consistent with Danon disease). Both Danon disease patients had primarily subendocardial LGE on CMR. One patient with a DCM phenotype had HCM pathologically. Results summarized in Table 1.

Conclusions:
Cardiac MRI can be a useful modality for the evaluation of underlying cardiomyopathy and should prompt appropriate genetic testing. Diffuse subepicardial LGE frequently accompanied the diagnosis of ARVC whereas a non-subepicardial pattern reflected alternative etiologies identified only through genetic testing.