bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4122284: HEART Score Classification of Major Adverse Cardiovascular Events in Patients with Diabetes Mellitus
Authors: Alhamaydeh Mohammad , Helman Stephanie , AlQaqaa Ahmed , Luo Huabin , Al-Zaiti Salah
Published: November 2024

Introduction:
Risk stratifying diabetes mellitus (DM) patients with chest pain in the emergency department (ED) can pose significant challenges because of atypical symptoms, non-specific ECG changes, and elevated baseline troponin levels. This study aims to evaluate HEART Score performance in DM versus non-DM patients.

Methods:
A prospective observational cohort study included chest pain patients transported by Emergency Medical Services to University of Pittsburgh Medical Center-affiliated hospitals. Data collection involved extracting data from electronic health records, including both DM and non-DM patients with chest pain. The HEART Score was retrospectively calculated by impartial assessors.The primary endpoint was major adverse cardiac events (MACE) within 30 days. This analysis included the classification performance of bivariate comparisons between the HEART Score and ACS outcomes using the area under the receiver-operator characteristic curve (AUC).

Results:
4,058 patients were included. 52.7% were male, 42% were white, there was a mean age of 59.24 years (16.13 SD), 28.63% had DM, and 22.1% had MACE. MACE prevalence was 19.7% in non-DM patients and 28% in patients with DM. The AUC demonstrated more robust discriminatory ability of the HEART Score in non-DM (AUC = 0.81) (95% CI 0.79-0.83) versus DM patients (AUC = 0.74) (95% CI 0.71-0.78) (p 0.001). The performance of HEART Score components, including history, age, and risk factors, exhibited better significant predictive capability for MACE in non-DM patients compared to DM patients. Conversely, the HEART-ECG and troponin components were not different between the DM and non-DM groups. The HEART Score demonstrates better performance in White individuals and females when contrasted with males and Black individuals. Nevertheless, these disparities do not reach statistical significance.

Conclusion:
The HEART Score performs differently in DM versus non-DM patients, with stronger discrimination observed in non-DM individuals. The troponin and ECG components exhibit poorer performance in diabetes mellitus (DM) patients within the context of the HEART Score. This underscores the complexity of risk assessment in DM patients with chest pain and suggests the necessity for further exploration and refinement of risk stratification strategies in this population.
Abstract 4122543: Can We Diagnose Ticagrelor-induced Dyspnea After Urgent Percutaneous Coronary Intervention with Cardiopulmonary Exercise Testing?
Authors: Giverts Ilya , Andreev Denis , Nanda Saumya
Published: November 2024

Background:
Ticagrelor has been reported to cause shortness of breath (SOB) in 6 to 9 % of patients. Precise mechanisms are not enirely understood. We hypothesize that cardiopulmonary exercise testing (CPET) may be helpful in clinical assessment of patients reporting SOB on ticagrelor.

Case presentation:
66-yo female with history of arterial hypertension, DM type 2 and prior MI presented with STEMI and successfully underwent urgent PCI of RCA and LAD. The patient received ticagrelor in loading dose followed by 90 mg b.i.d plus low-dose aspirin. Just after PCI she developed SOB with no evidence of acute cardiac or respiratory compromise. After discharge the patient continued to experience SOB impairing daily activities. In 6 months she was re-assessed. Clinical investigation (physical exam, blood tests, echo, CXR, spirometry) showed no abnormalities that could explain SOB. CPET despite good effort showed low VO
2
peak (7,8 ml*min/kg; 49% from predicted), undetectable anaerobic threshold (AT), severely impaired ventilatory efficacy (VE/VCO
2
=50,1) and marked hyperventilation (resting RER=1,0; PetCO
2
=18,0 mmHg at rest and 22,4 mmHg at peak load). Exercise EKG, blood pressure response, SpO
2
and breathing reserve were normal. Once the patient was switched from ticagrelor to clopidogrel she reported significant improvement. CPET one week after showed increase in VO
2
peak up to 12,5 ml/kg/min., AT of 11,1 ml*min/kg, better ventilatory efficacy (VE/VCO
2
=37,1) and less hyperventilation (PetCO
2
28,1 mmHg at rest and 28,8 mmHg at peak load). CPET performed one month later showed further improvement in VO
2
peak to 13,2 ml*min/kg, normal VE/VCO
2
and no signs of hyperventilation.

Discussion:
it is believed that ticagrelor-induced dyspnea can be driven by 2 potential mechanisms, first related to inhibition of adenosine reuptake, second - to sensory neuron P2Y12 inhibition. It occurs early after starting the medication and is not associated with structural cardiopulmonary abnormalities. Previous small data showed evidence of Cheyne-Stokes respiration during both night and day related to ticagrelor. Symptoms usually are dose-dependent and disappear after discontinuation of ticagrelor. In our case the patient demonstrated reversible hyperventilation and reduced exercise capacity associated with ticagrelor that was confirmed with CPET.

Conclusion:
CPET allows differentiating SOB in patients treated with ticagrelor. Further investigations are required to confirm this hypothesis.
Abstract 4122612: Validation of a Machine Learning Model for Fetal Echocardiographic Prediction of Critical Coarctation of the Aorta
Authors: McRae Robert , Magoon Matthew , Phillips Aaron , Virk Kathryn , Waschman Malika , Maskatia Shiraz , Pinto Nelangi , Boyle Patrick , Arya Bhawna
Published: November 2024

Background:
Current fetal echocardiographic (F-echo) metrics have inadequate specificity for confident prediction of neonatal critical coarctation of the aorta (CoA). Using single-center data, our machine learning model for the prediction of fetal CoA demonstrated improved accuracy compared to published F-echo metrics for critical CoA assessment. External validation of this model is needed.

Aim:
Validate a machine learning F-echo predictive model for CoA with an external patient cohort.

Methods:
Initial model training and testing were performed using retrospective single center data on 9 F-echo measurements for patients with prenatal concern for CoA. A random forest classifier with 80:20 split and 5-fold cross-validation predicted CoA intervention within 30 days of life. A SHapley Additive exPlanations (SHAP) analysis assessed the marginal contribution of each feature. The model was retrained using the 5 most influential F-echo features. External validation for this model was then performed using patients with prenatal concern for CoA retrospectively collected at a partner institution.

Results:
Inclusion criteria were met by 132 patients in the initial cohort and 64 patients in the external validation cohort, of whom 44% (n=58) and 25% (n=16) respectively had CoA requiring intervention. SHAP analysis for both cohorts demonstrated transverse to descending aorta angle as the most influential feature, followed by ascending to descending aorta angle (Figure 1A). Using internal cross-validation on the initial cohort, the area under the receiver operating characteristic curve (AUC) was 0.93 ± 0.05 (sensitivity 0.97, specificity 1.0) with an F1 score of 0.97 ± 0.03. Validation of the model with the external cohort produced an AUC of 0.87 (sensitivity 0.81, specificity 1.0) and an F1 of 0.90 (Figure 1B).

Conclusions:
A random forest classifier using F-echo features predicted neonatal critical CoA with higher accuracy than previously published metrics. The model maintained high accuracy when validated with an external patient cohort. Arch angles most significantly impacted the model’s accuracy. Future directions include prospective validation and converting the model to a distributable clinical calculator.
Abstract 4122679: Associations Between Recent and Cumulative Lifetime Cannabis Use and Sleep Health in Middle-Aged Adults: 35-Year Insights from the Coronary Artery Risk Development in Young Adults (CARDIA) and CARDIA Sleep Studies
Authors: Vu Thanh-Huyen , Knutson Kristen , Auer Reto , Jakob Julian , Lloyd-Jones Donald , Carnethon Mercedes
Published: November 2024

Background:
Cannabis use has become common, but its effects on sleep health—an important contributor to cardiovascular health—remain poorly understood. We investigated associations between recent and cumulative lifetime cannabis use and objective and subjective sleep measures in middle-aged adults.

Method:
We assessed recent cannabis use (last 30 days) repeatedly from young adulthood (age 18-30 at baseline in 1985-86) to middle age (after 35 years) in the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) study. Cumulative lifetime cannabis use (1 year = 365 days of use) was estimated by summing days of use during follow-up. At Year 35 (Y35), we obtained objective sleep measures (duration, efficiency, fragmentation, wake after sleep onset [WASO]) via 7-day wrist actigraphy from CARDIA Sleep Ancillary Study II. Subjective sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Robust regression models adjusted for Y35 age, sex, race, education, cumulative cigarette smoking, alcohol use, other substance use, physical activity, body mass index, sleep medication, and comorbidities. We also examined race, sex, and cigarette smoking status differences in associations.

Result:
Of 571 participants, mean age was 61.9 years; 65% were female, and 35% Black. Means (SD) for sleep duration, efficiency, fragmentation, WASO, and PSQI were 6.9 (1.1) hours, 90.5 (4.2)%, 20.6 (7.6)%, 43.5 (20.9) minutes, and 6.1 (3.6) scores, respectively. At Y35, 13.8% reported recent cannabis use, 56% reported former use, mean (SD) cumulative use was 1.6 (4.4) years. With adjustment, recent cannabis use was associated with longer sleep duration, lower efficiency, and higher WASO; former cannabis use was associated with longer sleep duration (Table). Compared to those with cumulative cannabis exposure years in the first quartile, fourth quartile users had longer sleep duration, lower efficiency, and higher WASO (β/p-value: 0.3/0.01, -1.2/0.01, and 8.9/<.001, respectively). PSQI was not associated with recent or cumulative cannabis use. Associations were similar across race, sex, and cigarette smoking status.

Conclusion:
Recent and cumulative lifetime cannabis use is associated with longer sleep duration and poorer sleep quality in objective, but not subjective, measures. Further longitudinal studies are needed to identify interventions aimed at improving sleep health and promoting cardiovascular health in cannabis users.
Abstract 4122840: Patient activation improves with a multi-component personalized mHealth intervention in older adults at risk of cardiovascular disease
Authors: Candelaria Dion , Cacciata Marysol , Serafica Reimund , Reyes Andrew Thomas , Lee Jung-Ah , Hildebrand Janett , Sta. Maria Axel , Stromberg Anna , Evangelista Lorraine
Published: November 2024

Background:
Patient activation, a person’s level of confidence, comprehension, and autonomy toward their health, is an essential goal of cardiovascular disease therapy. Previous research has shown a link between high levels of patient activation and better patient outcomes and experiences. However, whether individualized interventions such as a text-based mobile health (mHealth), improve patient activation is unclear. Research on patient activation in people at risk for cardiovascular disease and influential factors is minimal.

Aims:
This study aimed to 1) determine the effect of a multi-component mHealth intervention on patient activation and 2) examine its predictors among older adults at risk for cardiovascular disease.

Methods:
In this pilot randomized controlled trial, community-dwelling older adults with poor eating behaviors and reduced physical activity (n=54) were randomly assigned to the
GetFIT
(control) or
GetFIT+
(intervention) groups, with three- and six-month follow-up periods. The
GetFIT
group received healthy lifestyle counseling from a licensed health coach, a free commercial mHealth app with push alerts on physical activity, and an activity tracker for physical activity monitoring. The
GetFIT
+ group received the same components but had personalized text messages instead of push alerts. The 13-item Patient Activation Measure assessed patient activation; higher scores indicate better activation. Linear mixed-effects models were used to investigate between-group changes in outcomes across time.

Results:
The mean age was 65.4 ± 6.0 years; 61% were females and 61% were married. Baseline characteristics were comparable between groups. Significant improvements were observed in the
GetFIT+
group at three months (mean 3.53, 95% CI 0.11, 6.96; p=0.043) and six months (mean 4.37, 95% CI 0.91, 7.83; p=0.014), whereas improvements in the
GetFIT
group were non-significant. Adjusting for age, gender, education, employment, marital status, social support, smartphone confidence, and self-perceived health did not alter the results. Nevertheless, only social support was associated with higher patient activation overall (B=5.14, 95% CI 1.00, 9.27; p=0.015).

Conclusions:
People at risk for cardiovascular disease can improve their self-management abilities, knowledge, and confidence through personalized text messaging. Possessing social support is critical for maximizing the benefits of mHealth interventions.
Abstract 4123182: Women with Severe Congenital Heart Disease Have Increased Risk of Fetal/Neonatal Death
Authors: Patel Shayli , Raskind-Hood Cheryl , Ivey Lindsey , Haffner Alexandra , Book Wendy
Published: November 2024

Background:
Women with congenital heart defects (CHD) now routinely survive to reproductive age. Offspring of these women have more complications, including but not limited to inherited CHD, prematurity, small for gestational age (SGA), and fetal/neonatal death. In the United States, pregnancy-related complications and death are more common in Black women and their offspring compared to White women and their offspring, and in those residing in rural areas compared to urban areas.

Aims:
This study evaluates fetal/neonatal outcomes among women with CHD covered by Georgia Medicaid at the time of pregnancy, looking for differences among racial, geographic, and CHD severity groups.

Methods:
This retrospective cohort study identified 4581 women with CHD aged 11-50 with 6522 pregnancies (28.5% with severe CHD, 50.9% Black, 23.2% rural) covered by Georgia Medicaid between 2008-2019. Fetal/neonatal death, defined as fetal death after 20 weeks gestation, stillbirth, or neonatal death, was examined by CHD severity, race, and rurality using chi-square analysis. Multivariate logistic regression models were conducted adjusting for age at first documented pregnancy, social deprivation index (SDI), number of pregnancies, and multiple gestations.

Results:
Of 6522 pregnancies, 3.0% resulted in fetal/neonatal death. Fetal/neonatal death was more common in women with severe CHD compared to those with non-severe CHD (4.1% severe vs. 2.6% non-severe [aOR 1.39, 95% CI 1.02-1.85, p = 0.0018]). No significant differences were revealed in fetal/neonatal death between racial (3.3% Black vs. 2.8% White) or geographic (2.9% rural vs. 3.1% urban) groups after controlling for other variables.

Conclusions:
Compared to reported fetal and neonatal death rates among all U.S. pregnancies in 2019, women with CHD experienced a higher rate of fetal/neonatal death. Fetal/neonatal death was even more prevalent for women with severe CHD (4.1%) versus women with non-severe CHD (2.6%). Women with CHD, especially those with severe disease, have a high risk of fetal/neonatal death and should be monitored closely throughout the course of pregnancy.
Abstract 4123370: Distance to a Cardiac Imaging Center and Likelihood of Imaging Receipt: Defining Imaging Deserts
Authors: Spetko Nicholas , Song Yang , Orui Hibiki , Angell-James Constance , Cassidy Madeline , Blankstein Ron , Divakaran Sanjay , DI CARLI MARCELO , Wadhera Rishi , Strom Jordan
Published: November 2024

Background:
Cardiovascular imaging is critical for the diagnosis and management of cardiovascular disease. Whether geographic distance to a cardiovascular imaging center (CVIC) impacts access to care is unknown.

Methods:
We evaluated all Medicare beneficiaries (Fee-for-service and Medicare Advantage) from 2018-2022, excluding those < 65, without continuous Medicare enrollment in the previous year, individuals missing zip code of residence, or CVICs missing zip codes. We estimated distance from the centroid of an individual’s zip code of residence to the centroid of the zip code with the nearest CVIC (defined as > 10 imaging procedures/year). Multivariable regression models were used to estimate likelihood of imaging receipt by distance.

Results/Data:
A total of 64,260,530 individuals (age 73.0 ± 8 years, 54.6% female, 80.1% White) received care at 3,886 CVICS. The vast majority (95%) lived within 16 miles of a CVIC, but varied considerably by modality with substantially greater distances for cardiac CT, cardiac MRI, and PET (Median [IQR] distance in miles to CVIC, Echo: 3.4 [0.4-7.0]; SPECT: 3.8 [1.3-7.9]; cardiac CT: 8.1 [3.7-21.3]; cardiac MRI: 17.4 [7.3-43.3]; PET: 88.9 [26.2-194.6]). CVICs performing cardiac CT, cardiac MRI, or PET were nearly all in metropolitan locations. Likelihood of imaging receipt was triphasic: lowest within 0-10 miles of a CVIC (mainly metropolitan locations), greater within 10-15 miles, and then increasingly lower beyond 15 miles (
Figure 1
). Sites beyond the 16-mile threshold were predominantly in the Midwest and West (
Figure 2
).

Conclusions:
In this study of 64 million Medicare beneficiaries, 2018-2022, 95% of the US population was found to live within 16 miles of a CVIC, though varied by modality. While those living > 16 miles from a CVIC received less imaging, the lowest use was identified among individuals living in the same zip code as a CVIC, suggesting a possible disconnect between access to imaging care and proximity.
Abstract 4123373: Estimating obesity-attributable cardiovascular disease burden in the United States: a Bayesian network analysis
Authors: Sheth Sunny , Clark Samantha , Fabricatore Anthony , Faurby Mads , Houshmand-Oeregaard Azadeh , Toliver Joshua , Stevens Warren
Published: November 2024

Background:
Obesity is a known contributor to the development of cardiovascular disease (CVD) and increases the risk of subsequent mortality. To fully understand the burden of obesity, accurate information regarding its effects on CVD is necessary. Current estimates are limited by a focus on direct effects, use of non-representative data sources, and a reliance on inaccurate diagnosis codes.

Aim:
To determine the size of CVD burden attributable to obesity in the US and identify the mechanisms through which obesity affects CVD.

Methods:
This study used data collected from US adults (aged ≥35 years) participating in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020 and US Census projections. NHANES data were longitudinally adapted, and participants were excluded if they had missing data for weight history, risk factors, or a given outcome of interest. Bayesian networks (BNs) mapping out the relationship between risk factors and each outcome were constructed to estimate current CVD risk and expected CVD risk in the absence of obesity. Obesity-attributable CVD burden was then calculated for each outcome, and the direct and indirect pathways through which changes in CVD risk occur were characterized. A subgroup analysis was conducted in non-smoking participants aged ≤65 years for whom obesity is likely the primary CVD risk factor.

Results:
The final sample included data from approximately 29,000 participants. Of these, 1286 (4.3%) had a history of myocardial infarction (MI), 1283 (4.4%) had a history of stroke, 1092 (3.7%) had a history of heart failure (HF), and 1992 (6.7%) had a history of CVD (composite of MI, stroke, angina, coronary heart disease, and HF). Results from the fitted BN indicate that 21% of MI, 16% of stroke, 38% of HF, and 19% of CVD cases were attributable to obesity, with ≥80% of this burden due to the effect of obesity on intermediate risk factors (hypertension, type 2 diabetes, and prior cardiovascular events). In the subgroup analysis, the obesity-attributable CVD burden was approximately twice as high for non-smokers aged ≤65 years, with 39% of MI, 32% of stroke, 65% of HF, and 38% of CVD cases attributable to obesity.

Conclusion:
Through a sophisticated network modeling approach, we generated estimates of obesity-attributable CVD burden in the US. Results highlight the importance of obesity as a CVD risk factor, particularly in younger non-smokers, and provide insight into the nature of this relationship.
Abstract 4123391: CardioMEMS and Mavacamten: A Synergistic Approach in Managing Hypertrophic Obstructive Cardiomyopathy with HFpEF Phenotype
Authors: Iftikhar Momina , Wan Ningxin
Published: November 2024

Introduction:
Mavacamten is a cardiac myosin inhibitor that has been approved for obstructive hypertrophic cardiomyopathy (oHCM). The CardioMEMS PA (pulmonary artery) sensor allows remote pulmonary artery diastolic (PAD) pressure monitoring to adjust diuresis in heart failure with preserved ejection fraction (HFpEF). We present the case of a patient with oHCM and HFpEF where data extrapolated from CardioMEMS provided valuable insight to the hemodynamic impact of cardiac myosin inhibitors.

Case:
A 66-year-old female with hypertension, obesity and oHCM presented with worsening dyspnea and was evaluated for septal myectomy. However, surgery was deferred because of decompensated HFpEF, as evidenced by significant leg edema on exam, and severely elevated left and right-side filling pressure, with restrictive physiology on right heart catheterization. A CardioMEMS PA sensor was implanted to guide decongestion, however, escalation of diuresis was limited due to severe left ventricular outflow tract (LVOT) obstruction. PAD remained elevated at 20-30 mmHg. Due to the refractory LVOT obstruction and despite the use of maximally tolerated beta blockers, Mavacamten was initiated and escalated according to protocol. LVOT obstruction resolved on follow up echocardiogram. Without any adjustment in her diuretic regimen, her PAD decreased to 15-20 mmHg. On follow-up visit, the patient reported improvement in dyspnea and reduction in lower extremity edema.

Discussion:
Managing oHCM is challenging, particularly when complicated by HFpEF. Mavacamten has shown promise in reducing LVOT gradients and improving symptoms in oHCM. However, managing fluid status in these patients can be difficult due to the risk of exacerbating LVOT obstruction while optimizing filling pressures. Our case provides direct evidence that treating LVOT obstruction with a cardiac myosin inhibitor leads to improvement in decompensated heart failure, as evidenced by the reduction in PAD.

Conclusion:
Addressing LVOT obstruction is key to decongesting and managing heart failure in oHCM patients. In our case, the use of CardioMEMS PA sensor system allowed a novel perspective of assessing hemodynamic impact of cardiac myosin inhibitors.
Abstract 4123540: Cardiovascular Health and Cancer Incidence and Mortality: NHANES-III and -Continuous study
Authors: Elsayed Omar , Hyma Kunhiraman Harikrishnan , Okwuosa Tochi , Addison Daniel , Cortes Jorge , Dent Susan , Ganatra Sarju , Bevel Malcolm , Al-Kindi Sadeer , Hedrick Catherine , Harris Ryan , Nasir Khurram , Weintraub Neal , Wang Xiaoling , Guha Avirup
Published: November 2024

Background:
Cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. Limited evidence is available regarding the relationship between CVD, cardiovascular risk factors (CVRF), and cancer mortality; and how CVRF further modify that relationship.

Methods:
The first part included 438 and 2100 CVD patients aged 65+ from NHANES-III and Continuous (1999-2016) datasets, respectively. Competing risk models with subdistribution hazards ratio (aHR) were used to identify risk factors for cancer incidence.

The second part included 44,591 adult individuals from NHANES-Continuous merged with Medicare and National Death Index mortality data until the end of 2018. We included individuals with no history of cancer at baseline. We used competing risk modeling to test the relationship between CVD at baseline and cancer mortality. We also conducted a comprehensive risk factor analysis.

Results:
In the first part (Figure), females in NHANES-III had lower cancer risk (aHR 0.39, P=0.001) compared to males. Poor physical activity was associated with increased cancer risk in both datasets (aHR 2.59 in NHANES-III, aHR 1.59 in Continuous). In NHANES-Continuous, age (aHR 1.07, P<0.001) and current smoking (aHR 2.55, P=0.001) showed a significant association with developing cancer. No other factors investigated showed significant associations.

In the second analysis (Table), the included sample size represented 1,738,423,317 individuals (52% females, 67% non-Hispanic Whites, and 9% Hispanics). Competing risk modeling showed a significantly higher risk of cancer mortality in individuals with CVD (aHR 1.37, 95% CI 1.07-1.76, P=0.01) after adjusting for age, sex, and race/ethnicity. Notably, cancer mortality increased with aging (aHR 1.08, 95%CI 1.05-1.11, P<0.0001), current smoking status (aHR 6.78, 95%CI 3.43-13.42, P<0.0001), and obesity (aHR 2.32, 95%CI 1.13-4.79, P=0.02). Finally, a significant interaction (P=0.034) was found where those with CVD and obesity showed higher cancer mortality than those with normal BMI (aHR, 95%CI 1.03-2.91, P=0.04).

Conclusions:
Our study highlights the close relationship between cardiovascular health and cancer, including among CVD patients. Our findings suggest that physical activity and obesity may play a significant role in cancer incidence and mortality among the general population and CVD patients. These findings emphasize the need for more proactive approach in the management of shared risk factors for CVD and cancer.
Abstract 4123814: Long-term Incidence of Cardiovascular Events and Mortality in Patients with and without Weight Regain After Bariatric Surgery in the Swedish Obese Subjects Study
Authors: Carlsson Ekander Lena , Sjoholm Kajsa , Arnetorp Ida , Peltonen Markku , Carlsson Bjorn
Published: November 2024

Background:
Obesity shortens life expectancy, while bariatric surgery causes large weight loss and increases median life expectancy by approximately 3 years. However, weight regain after bariatric surgery is common, and its impact on health remains uncertain. In this study, we examined whether weight regain following bariatric surgery is associated with long-term cardiovascular outcomes and mortality.

Methods:
We analyzed patients undergoing bariatric surgery in the prospective Swedish Obese Subjects study, aged 37-60 with a BMI≥34 (men) or ≥38 (women), recruited 1987-2001. Patients who regained ≥20% of their 1-year weight loss after 4 years (regain group; n=715) were compared to those who regained less (maintenance group; n=631). Information on cardiovascular disease as well as overall and cardiovascular mortality was obtained from the Swedish Population and Address Register, the Swedish Cause of Death Register, and the Swedish National Patient Register. Median follow-up was 27 years.

Results:
Average weight change from year 1 to year 4 was +12.8 kg and -0.2 kg in the regain and maintenance groups, respectively. The incidence of major adverse cardiovascular events (myocardial infarction, stroke and heart failure) was similar between the groups, with 185 events in the regain group and 137 in the maintenance group. This corresponds to 11.6 events per 1000 person-years (95% CI: 10.1-13.5) for the regain group, and 10.0 events per 1000 person-years (95% CI: 8.3-12.4) for the maintenance group. The adjusted HR was 1.16 (95% CI: 0.92-1.46), p=0.213.

During follow-up, there were 216 deaths in the regain group and 184 in the maintenance group, resulting in nearly identical overall mortality rates of 12.4 per 1000 person-years for both groups (95% CI for regain: 10.9-14.2, maintenance: 10.9-14.3). The number of deaths from cardiovascular disease was 77 in the regain group and 57 in the maintenance group, corresponding to similar incidence rates of 4.4 per 1000 person-years (95% CI: 3.5-5.5) and 3.8 per 1000 person-years (95% CI: 3.0-5.0), respectively (p=0.550).

Conclusions:
The incidence of major adverse cardiovascular events, as well as total and cardiovascular mortality, was similar between the weight regain and maintenance groups. This suggests that the beneficial association between bariatric surgery and reduced cardiovascular events persists despite weight regain.
Abstract 4123849: Respiratory Syncytial Virus (RSV) Cases Involving Hospitalization Are Associated with an Increased Risk of Myocardial Infarction and All−Cause Mortality Among Adults Aged 50 Years and Older
Authors: Singer David , Wang Yan , Wu Aozhou , La Liz , Gerber Susan , Liu Hongjiao , Betts Keith
Published: November 2024

Background:
Older adults and adults with comorbidities are at increased risk for severe respiratory syncytial virus (RSV) disease and related complications.

Aims:
To estimate the risk of myocardial infarction (MI) and all−cause mortality among adults aged ≥50 years hospitalized with RSV compared to those with no recent acute respiratory illness (ARI) and those hospitalized with influenza.

Methods:
Data from Optum’s de−identified Clinformatics® Data Mart Database were analyzed (October 2015–June 2023) in this retrospective cohort study. Adults aged ≥50 years with ≥12 months of continuous enrollment were assigned to cohorts based on RSV or influenza hospitalization (from ICD−10 codes; RSV and flu cohorts) or no recent ARI (control cohort). Index dates for RSV and flu cohorts were the start of an ARI that included hospitalization. Baseline characteristics were measured in the 12 months pre−index. MI (from ICD−10 codes) and all−cause mortality were measured during follow−up and compared between cohorts using time−varying coefficient multivariable adjusted Cox models (MI results accounted for the competing risk of death).

Results:
In the RSV cohort (n=14,759), mean age (76.5 years) and mean Charlson comorbidity index (CCI; 3.3) were higher than the flu (n=77,468; 75.4 years, CCI=2.9) and control (n=73,795; 69.5 years, CCI=1.0) cohorts. Adjusted HRs (95% CI) for MI and all−cause mortality risk were significantly higher in the RSV vs control cohort across follow−up, ranging from 30.96 (26.22–36.54) within 30 days post−index to 2.26 (2.04–2.51) >365 days post−index for MI and 10.77 (9.19–12.63) within 30 days post−index to 2.29 (2.18–2.42) >365 days post−index for mortality. Compared to the flu cohort, adjusted MI and mortality risk in the RSV cohort were lower during the 30 days post−index (MI: 0.87 [0.82–0.92]; mortality: 0.84 [0.78–0.90]) but higher >365 days post−index (MI: 1.11 [1.01–1.22]; mortality: 1.05 [1.01–1.10]).

Conclusion:
MI and all−cause mortality risk were higher for hospitalized RSV cases compared to controls. Smaller differences in outcomes were observed when comparing hospitalized RSV cases with hospitalized influenza cases, with varying direction over time. With existing evidence of increased MI and mortality risk after influenza and these findings on MI and mortality risk after RSV, future research should aim to further understand the impact of RSV on cardiovascular outcomes and assess the role of RSV prevention in lowering the risk of MI and mortality.
Abstract 4123872: Unsupervised clustering analysis of large-scale proteomics data identifies molecular phenogroups of heart failure in a population-based cohort
Authors: Downie Carolina , Shearer Joe , Kuku Kayode , Hashemian Maryam , Bielinski Suzette , Joo Jungnam , Roger Veronique
Published: November 2024

Background:
Heart failure (HF) is a heterogeneous syndrome with high mortality. Previous work characterizing HF subgroups primarily relied on clinical data to cluster patients, an approach constrained by the boundaries of documented clinical features. Clustering based on biomarker data, such as proteomics, may provide insights into underlying molecular processes. However, few studies have used this approach, and all used targeted cardiovascular proteomics panels and a restricted HF ejection fraction group.

Hypothesis:
We used unsupervised clustering analysis to characterize molecular phenogroups in a population-based HF cohort using a large-scale array of circulating plasma proteins. We hypothesized that distinct proteomic-defined phenogroups would exhibit differences in clinical characteristics, mortality, and protein expression.

Methods:
We measured 7151 SOMAmers (Slow off-rate modified aptamers) targeting human proteins via the SomaLogic 7K SomaScan assay in 1351 HF patients. After feature selection, 831 SOMAmers were used in k-means clustering of patients via R package “ConsensusClusterPlus.” Phenogroups were compared for clinical characteristics, all-cause mortality, and protein expression.

Results:
Three phenogroups were identified, exhibiting different clinical characteristics (
Table 1
) and survival probabilities (5-year survival probability in phenogroup 1: 65% [61%, 68%], phenogroup 2: 45% [40%, 51%], and phenogroup 3: 26% [22%, 30%]). In covariate-adjusted Cox models, membership in phenogroups 2 and 3 was significantly associated with increased rate of mortality compared to phenogroup 1. Phenogroups did not differ by ejection fraction or New York Heart Association class. Pathway overrepresentation analysis of differentially expressed SOMAmers identified pathways associated with inflammatory response and immune cell trafficking.

Conclusions:
Unsupervised clustering analysis using large-scale proteomics data identified three HF phenogroups with different proteomic signatures, clinical characteristics, and outcomes. Future work is necessary to elucidate how molecular differences contribute to heterogeneity in HF to improve risk stratification beyond current recommended clinical guidelines.
Abstract 4123886: Health Disparities in Quality of Life Among Black Patients with Heart Failure: The Roles of Depressive Symptoms and Functional Status
Authors: Thapa Ashmita , Kang JungHee , Latimer Abigail , Wu Jia-Rong , Chung Misook , Biddle Martha , Lin Chin-Yen , Moser Debra
Published: November 2024

Background:
Black patients with heart failure (HF) have a higher physical and psychological distress which disproportionately worsens their health and quality of life (QOL) than those from other racial/ethnic groups. Black patients less commonly receive optimal therapy for HF than white patients, which can result in poorer functional status. Black patients report higher levels of depressive symptoms. Higher levels of depressive symptoms can further worsen functional status and lower QOL.

Hypothesis:
We hypothesized that depressive symptoms would predict QOL in Black patients with HF and that this relationship would be mediated by functional status.

Methods:
Using the RICH Heart Program HF Database, we included all 226 Black patients (57±12 years old, 49% male) with HF, who completed the Patient Health Questionnaire-9 to measure depressive symptoms, the Duke Activity Status Index for functional status, and the Minnesota Living with Heart Failure Questionnaire for QOL. Mediation analysis was performed using the PROCESS macro.

Results:
Depressive symptoms were directly associated with QOL (effect coefficient [c’] =2.386, 95% confidence interval [CI] = 2.549, 3.450). There was a significant indirect effect of depressive symptoms on QOL mediated by functional status (ab=0.614, 95% CI [0.406, 0.856]). Those with worse depressive symptoms had lower functional status (a = -0.901, p< 0.001), in turn, lower functional status was associated with worse QOL (b = -0.681 p<0.001).

Conclusions:
Depressive symptoms are directly associated with QOL and there also is an indirect association, mediated by functional status in Black patients with HF. Inequities in the management of HF among Black patients that contribute to these findings must be explored as the causes of the disparity in depressive symptoms are not yet known.
Abstract 4123956: Upgrade to Implantable Cardioverter-Defibrillator in Patients Diagnosed with Cardiac Sarcoidosis after Permanent Pacemaker Implantation for High-Grade Atrioventricular Block
Authors: Austin Brett , Rosenbaum Andrew , Abou-Ezzeddine Omar , Giudicessi John , Bois John , Bratcher Melanie , Kapa Suraj , Deshmukh Abhishek , Siontis Konstantinos
Published: November 2024

Introduction:
Unexplained high-grade AV block (AVB) in patients age <65 years is among the salient features of cardiac sarcoidosis (CS). Guidelines recommend that CS patients with high-grade AVB should receive an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) rather than a permanent pacemaker (PPM). However, in clinical practice, CS may be recognized after PPM implantation for high-grade AVB.

Aims:
To evaluate the characteristics and outcomes of patients diagnosed with CS after PPM implantation for high-grade AVB and assess the decision-making and rationale for upgrade to ICD/CRT-D.

Methods:
Retrospective review of the Mayo Clinic Sarcoid Registry (n=848) was performed to identify all patients for which a PPM was implanted for high-grade AVB prior to the diagnosis of CS. Baseline clinical and imaging characteristics were collected during index evaluation at our institution. Decision-making for ICD upgrade, lead management strategy, immunosuppression initiation, and outcomes were assessed.

Results:
Overall, 29 of 848 (3.4%) of CS patients (62% probable/definite CS; 77% male; median (IQR) age 56 (48-61) years; and median (IQR) LVEF 58% (50-62) received a PPM for high-grade AVB prior to a CS diagnosis.

Median (IQR) interval between PPM implant and index evaluation was 10 (3-23) months. Eight of 29 patients underwent upgrade to ICD (n=4) or CRT-D (n=4). Among them, the pacing lead was extracted in 4. All patients were upgraded for primary prevention of sudden cardiac death (SCD), with 3 of them also having LVEF<50% requiring upgrade to CRT-D. Twenty-two (79%) patients in the total cohort were treated with immunosuppression. During median (IQR) follow-up 37 months (11-74), 1 patient in the upgrade group had sustained VT appropriately treated with anti-tachycardia pacing. No events were documented among patients in the non-upgrade group. At last follow-up, 6 (75%) patients in the upgrade group and 12 (57%) in the non-upgrade group were pacemaker dependent. Median LVEF change was 0% in patients who underwent upgrade to CRT-D and –0.2% in those who underwent upgrade to ICD or no upgrade.

Conclusions:
In this cohort of patients diagnosed with CS several months after a PPM had been implanted for high-grade AVB, incident VT/VF was infrequent with contemporary CS management. In the absence of other SCD risk factors, CS patients who received a PPM for high-grade AVB prior to their CS diagnosis may not require ICD upgrade.
Abstract 4124065: Clonal Hematopoiesis of Indeterminate Potential (CHIP) in Chronic Coronary Artery Disease: A Report from the ISCHEMIA Trials Biorepository
Authors: Muller Matthew , Liu Richard , Hu Jiyuan , Held Claes , Kullo Iftikhar , McManus Bruce , Newby L. Kristin , Sidhu Mandeep , Bangalore Sripal , Reynolds Harmony , Hochman Judith , Maron David , Ruggles Kelly , Berger Jeffrey , Newman Jonathan
Published: November 2024

Introduction:
CHIP is associated with CAD and mortality. The prognostic relevance of CHIP for high-risk patients with confirmed CAD is unknown.

Hypothesis:
CHIP variants are associated with cardiovascular (CV) events and mortality in high-risk patients with known CAD in the ISCHEMIA Trials Biorepository.

Methods:
895 ISCHEMIA and ISCHEMIA-CKD (hereafter, ISCHEMIA Trials) participants with moderate-severe ischemia and next-generation sequencing performed for CHIP variant allele fractions of ≥2% (CHIP) and ≥10% (large CHIP) were included. Unadjusted and multivariable adjusted (age, sex, diabetes, eGFR not on HD, HD, and LVEF) associations of CHIP and large CHIP with a) ISCHEMIA Trials initial phase primary endpoint (CV death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, RCA) and b) ISCHEMIA Trials combined initial and extended follow-up phase (hereafter, Cumulative) endpoint of all-cause death .

Results:
Median (IQR) age of sequenced participants was 67 (56 – 79) years, 19% were female, 83% white, and 6% Hispanic. Hypertension (84%), diabetes (45%) and obesity (47%) were common, 26% had an eGFR <60 ml/min/1.73m
2
. The prevalence of CHIP and large CHIP was 23% and 7%, and both increased with age (
Figure 1a
). CHIP mutations in DNMT3A were detected in 106 (12%), TET2 CHIP in 44 (5%), and ASXL1 CHIP in 21 (2%) participants (
Figure 1b
). DNMT3A, TET2, and CREBBP mutations collectively comprised 199 (52%) of overall CHIP mutations, including individuals with multiple mutations in the same gene (N
overall
= 385); 67 participants (7%) had mutations in >1 gene. Over 3.1 years of RCT follow-up there were 135 (20%), 32 (16%) and 15 (18%) primary endpoints for no CHIP, CHIP and large CHIP, respectively. Over 6.8 years of EXTEND follow-up, there were 126 (18%), 47 (23%) and 24 (29%) deaths in the no CHIP, CHIP and large CHIP groups, respectively. After multivariable adjustment there was no association between CHIP or large CHIP and CV events or mortality (
Figure 1c
).

Conclusion:
Neither CHIP nor large CHIP was associated with adverse outcomes in 895 high-risk individuals with confirmed CAD, despite a high prevalence of these mutations.
Abstract 4124084: Nitric Oxide Releasing Bionanomatrix Gel For Dialysis Arteriovenous Fistula Maturation
Authors: Jun Ho-wook , Hwang Patrick , Somarathna Maheshika , Chen Jun , Sherwood Jennifer , Brott Brigitta , Lee Timmy
Published: November 2024

Introduction:
About 600,000 patients in the US suffer from end-stage renal disease (ESRD); more than 75% of ESRD patients undergo dialysis. Vascular access dysfunction is a major cause of morbidity and hospitalization in dialysis patients. Arteriovenous fistulas (AVFs) are considered the gold standard of vascular access for dialysis. However, about 60% of AVFs fail to mature because of early venous neointimal development and poor vasodilation and vascular wall remodeling. Therefore, to promote AVF maturation, we propose the application of a nitric oxide (NO) releasing nanomatrix gel, or ‘NO gel’, on the created AVF. The NO gel is composed of peptide amphiphiles (PA), which contain a polylysine (KKKKK) group to form NO-donating residues. In this study, we test our hypothesis that the NO gel applied at AVF can promote AVF maturation by decreasing venous intimal hyperplasia, enhancing vasodilation and vascular outward remodeling in porcine model.

Materials and Methods:
PA containing with KKKKK was synthesized and charged with NO to produce NO gel. For
in vivo
studies, AVFs in porcine were created by connecting the jugular vein and carotid artery. The NO gel was applied perivascularly over the AVF anastomosis. And the pigs were sacrifice after 35 days. AVF hemodynamics were evaluated using MRI-based computed fluid dynamics analysis.

Results:
We found significant decrease in neointimal hyperplasia in porcine AVFs treated with NO gel compared to the control groups. Additionally, the percentage of open lumens was significantly higher in the NO gel-treated group. It is indicated that veins in NO treated group showed less fibrosis as an less type I collagen I produced in the NO treated group than control. Also, the NO gel significantly improved hemodynamics and vascular remodeling of porcine AVFs compared to the control.

Conclusion:
These results suggest that the NO gel plays a crucial role in AVF maturation by reducing intimal hyperplasia and stenosis following AVF creation in a pig model. When intimal hyperplasia is reduced and the vessel is dilated, less tensile force of blood flow is applied on the arterialized vein, directing the AVF to appropriate maturation.
Abstract 4124120: Rare but Deadly - Eosinophilic Myocarditis in a Patient with Eosinophilic Granulomatosis Polyangiitis
Authors: Shetty Samantha , Shah Priya , Kim Yee Soo , De La Cruz Tejada Angel , Radakrishnan Ankitha , Srikureja Anya , Jacobi Adam , Beasley Mary , Mahmood Kiran
Published: November 2024

Eosinophilic myocarditis (EM) is a rare inflammatory myocarditis characterized by eosinophilic infiltration of myocardial tissue. Despite the high mortality rate, EM is frequently underdiagnosed and is often first identified in postmortem studies. We share a case of EM as an early manifestation of newly diagnosed eosinophilic granulomatosis polyangiitis (EGPA). The patient is a 46-year-old female with a past medical history of ulcerative colitis and adult-onset asthma who presented to the emergency department with a 2–3-week history of worsening positional chest pain radiating to the left upper extremity. Associated symptoms include 3 months of fatigue, headaches, right foot neuropathy, urticaria, and B-symptoms. Prior to admission, the patient was started on empiric prednisone for presumed EGPA. Initial lab work on admission was notable for elevated troponin (602 ng/L), hyper-eosinophilia (19.5%), thrombocytosis (680K/uL), and elevated ESR (42 mm/h) that have improved since initiation of prednisone. Transthoracic echocardiogram revealed a newly reduced LVEF of 40% with basal and mid-septal wall motion abnormalities. Cardiac catheterization showed normal coronaries confirming the diagnosis of non-ischemic cardiomyopathy. Late gadolinium enhancement in cardiac MRI was seen in basal to mid segments with patchy pericardial enhancement, meeting the Lake Louise criteria for myocarditis. An endomyocardial biopsy showed substantial myocardial infiltration with lymphocytes, histiocytes and eosinophils, confirming the diagnosis of EM. After multidisciplinary team discussion with cardiology and rheumatology, the patient was started on guideline-directed medical therapy for her HFrEF and pulse dose steroids with a prolonged taper and cyclophosphamide. She is tolerating her treatment well. This case highlights the importance of early recognition, comprehensive assessment and targeted treatment for EM depending on its underlying etiology. In the case of autoimmune dysfunction, it involves a combination of immunosuppressive and symptomatic therapy. Ongoing research is crucial to enhance our understanding and improve clinical outcomes, like arrhythmias and cardiogenic shock, for this complex condition.