bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4125939: Bayesian re-analysis of the STeroids to REduce Systemic inflammation after infant heart Surgery (STRESS) trial
Authors: Hill Kevin , Koerner Jake , Hong Hwanhee , Li Jennifer , Jacobs Marshall , Kannankeril Prince , Baldwin Scott , Jacobs Jeffrey , Hornik Christoph , Benscoter Alexis , Van Bergen Andrew , Anderson Brett , Blasiole Brian , Overman David , Vener M D David , Graham Eric , Husain Adil , Wald Eric , Scott John , Kim John , Swartz Michael , Eghtesady Pirooz , Butts Ryan , Karamlou Tara , OBrien Sean
Published: November 2024

Background:
Prophylactic steroids are often used to reduce the systemic inflammatory response to cardiopulmonary bypass in infants undergoing heart surgery. The STRESS trial found that the likelihood of a worse outcome did not differ between infants randomized to methylprednisolone vs placebo in a risk-adjusted primary analysis (adjusted odds ratio [OR], 0.86; 95% CI, 0.71 to 1.05; P=0.14). However, secondary unadjusted analyses showed possible benefits with methylprednisolone. We re-analyzed the STRESS trial using Bayesian analytics to assess probability of benefit with methylprednisolone.

Methods:
We used a covariate-adjusted proportional odds model using the original STRESS trial model covariates and primary outcome (a ranked composite of death, transplant, major complications and post-op length of stay). We assessed effect thresholds from OR 0.6 to 1.25 (OR <1 conveys benefit, OR >1 conveys harm). We assumed a neutral probability of benefit vs harm with weak prior belief (SD of the normal prior distribution = 0.425). In sensitivity analyses, we evaluated pessimistic (5%-30% prior likelihood of benefit), neutral and optimistic (70%-95% prior likelihood of benefit) prior beliefs, and controlled strength of prior belief as weak (SD = 0.425), moderate (SD = 0.215) and strong (SD = 0.135). We compared posterior distribution of the OR under these priors with the reference results under the vague prior distribution. Analyses consisted of 10 Markov Chain Monte Carlo simulations each consisting of 2000 iterations with a 1000 iteration burn-in to ensure proper posterior convergence.

Results:
In primary analysis, the posterior probability of benefit from methylprednisolone was 92% and the probability of harm was 8%. The mean absolute benefit was 12%. In sensitivity analyses, the probability of benefit was ≥ 79% for all informative priors except the most pessimistic (Table/Figure).

Conclusion:
In Bayesian re-analysis of the STRESS trial, probability of benefit with prophylactic methylprednisolone is high and harm is unlikely. Assessing probability of benefit or harm may be more informative than frequentist analytics relying on a p-value threshold. Another advantage is the ability to consider a range of prior evidence.
Abstract 4125957: Feasibility and Acceptability of Behavioral Weight Loss Programs for Men in Trade and Labor Occupations
Authors: Crane Melissa , Feit Catherine , Yeh Chen , Gonzalez Mariangeline , Appelhans Brad
Published: November 2024

Objective:
Men who work in trade and labor occupations experience high rates of obesity and related cardiovascular disease due to high rates of sedentary leisure time and poor diet. Despite this, they are underrepresented in weight control programs. This pilot randomized trial evaluated the feasibility and acceptability of a 6-month program tailored to this occupational group versus a non-tailored standard-of-care behavioral weight loss program.

Methods:
Men with overweight or obesity working in trade and labor occupations were randomly assigned to either a tailored program or the DPP Group Lifestyle Balance program delivered via 16 one-hour virtual group sessions. In-person assessments were conducted at baseline, 3, and 6 months. Semi-structured interviews and self-report were used to assess the acceptability of the interventions. Feasibility was assessed using recruitment metrics and proportion group sessions and study assessments completed.

Results:
Participants (N = 28; median 44.0 years, interquartile range (IQR): 38.5-54.5), median 31.8 BMI, IQR 31.1-39.6) were recruited into the study over 7 months, and 71% and 79% were retained for assessments at 3 and 6 months, respectively. Overall, participants attended a median of 7 of the 16 group sessions (IQR 2.5-11.5). The tailored group completed a median of 11 of 16 weekly online progress reports (IQR 5-15). All participants reported that they would recommend the programs to other men and felt confident that they would continue using the strategies learned in the programs. Though the trial focused on feasibility rather than efficacy, median weight losses at 6 months were -3.0% in the tailored group (95% CI -9.3, -0.6) and -1.9% in the standard group (95% CI -7.4, 2.0).

Conclusions:
Results suggest that both the tailored and standard weight loss interventions were well received by this group, but engagement was low. Future research should focus on understanding how to increase engagement rather than exclusively tailoring the program to this occupational group to enhance this group's involvement with cardiovascular disease prevention programs.
Abstract 4125996: Outcomes Of Transvenous Lead Extraction As a Function Of Lead Dwell Time: Does Risk Plateau With Very Old Leads?
Authors: Mekary Wissam , El-Chami Mikhael , Bhatia Neal , Lloyd Michael , Westerman Stacy , Shah Anand , Leal Miguel , Delurgio David , Patel Anshul , Tompkins Christine , Merchant Faisal
Published: November 2024

Introduction:
Longer lead dwell time is associated with worse outcomes during transvenous lead extraction (TLE). It has been suggested that risk may plateau beyond a certain dwell time but data on this are lacking.

Methods:
We identified all TLE procedures at Emory Healthcare from 2007-2023. Clinical characteristics and procedural details were collected from medical records. Procedural outcomes were reported using the 2017 HRS/ACC/AHA consensus statement on TLE. Procedural success was defined as complete removal of all targeted lead hardware without any major complications. Clinical success was defined as retention of a small portion (<4 cm) of targeted lead which does not negatively impact the outcome of the procedure.

Results:
We identified 1,717 TLE procedures. Mean patient age at extraction was 64.6 ± 15.1 yrs, 61.4% were male, 53% had ICD leads and 21% had CRT systems. Extraction indications included lead malfunction (46%), infection (38%) and venous occlusion with need for system upgrade (11%). The dwell time of the oldest lead targeted for extraction was < 1 yr (n=326, 19%), 1-5 yrs (n=633, 36.9%), 5-10 yrs (n=467, 27.2%), 10-15 yrs (n=178, 10.4%), 15-20 yrs (n=71, 4.1%) and >20 yrs (n=42, 2.4%). Procedural and clinical success rates decreased with longer lead dwell time (Figure 1A). Success rates were excellent (>95%) among leads <5 yrs old whereas success rates dropped to the 70-75% range for leads >20 years old. Most clinical failures among very old leads were due to inability to remove all lead material in the setting of infection. Across the entire cohort, the major complication rate was 1.3% and procedural death rate was 0.5%. Complications increased with increased lead dwell time (Figure 1B). Peri-procedural death occurred in 2.8% of cases with dwell times of 15-20 yrs. There were no major complications or deaths among dwell times of >20 yrs, however, the vast majority of these were pacemakers, not ICDs.

Conclusion:
TLE success rates decrease and complication rates increase with increased lead dwell time, without any clear evidence of a plateau effect. These data have implications for making decisions about abandoning vs. extracting redundant leads.
Abstract 4126000: The Association of Cardiologist Vertical Integration With Care Quality, Patient Outcomes, and Utilization
Authors: Moghtaderi Ali , Magid David , Masoudi Frederick , Luo Qian , Black Bernard , Kini Vinay
Published: November 2024

Introduction:
U.S. healthcare has experienced substantial growth in vertical integration (physicians employed by hospitals), but little is known about its effect on patient care.

Aims:
To assess the association between cardiologist vertical integration and patient outcomes, care quality, and utilization among patients hospitalized with incident acute myocardial infarction (AMI) or heart failure (HF).

Methods:
We used a sample of all Medicare fee-for-service beneficiaries hospitalized with incident AMI and a 75% sample of beneficiaries hospitalized with incident HF between 2008-2019. We identified the accountable cardiologists that cared for these patients and determined their integration status using tax identification numbers. We used difference-in-differences methods to compare outcomes for patients treated by integrated cardiologists after switching from non-integrated to integrated practice, to outcomes for patients treated by cardiologists who remained non-integrated. Patient outcomes were in-hospital mortality, 30-day mortality, and 30-day readmission. Quality measures were the proportion of patients that received 1) a guideline-recommended test to assess cardiac function and 2) a 30-day follow-up clinic visit. Utilization measures were length of stay and the proportion of AMI patients receiving percutaneous coronary intervention. Models were adjusted for time trends and patient, hospital, and cardiologist characteristics.

Results:
The proportion of U.S. cardiologists employed by hospitals increased from 26% in 2008 to 61% in 2018. We identified 186,052 AMI patients and 259,849 HF patients cared for cardiologists who switched to integrated practice and 168,052 AMI patients and 245,769 HF patients cared for by non-integrated cardiologists. Patients were similar in age, sex, race/ethnicity, and comorbidities. We found no significant differences in clinical outcomes (e.g., adjusted difference in 30-day mortality 0.03% [95% CI = -0.39%, 0.45%] for AMI and -0.05% [-0.37%, 0.27%] for HF patients); no differences in most quality metrics, and no differences in utilization between patients treated by integrated versus non-integrated cardiologists.

Conclusions:
We found minimal evidence that cardiologist employment by hospitals improves care quality or outcomes. Regulation of vertical integration should focus on other effects of integration such as higher prices paid by insurers.
Abstract 4126333:
TRPC6 A404V
is a gain-of-function variant associated with doxorubicin-induced cardiotoxicity in patients
Authors: Wu Ying , Sun Xiaojing , Wang Ruxing , Norton Nadine , Lee Hon-Chi , Lu Tong
Published: November 2024

Background:
Gain-of-function mutations in the canonical transient receptor potential 6 (TRPC6) channel contribute to heart failure (HF) and focal segmental glomerulosclerosis in humans. Our GWAS results indicated that the
TRPC6 A404V
variant, having a minor allele frequency of 12% in the population, is associated with doxorubicin-induced cardiotoxicity. However, the underlying ionic mechanisms of this variant have not been fully examined.

Methods:
Combining patch clamp recording, site-directed mutagenesis, and in-silico analysis, we evaluated the
TRPC6 A404V
variant function.

Results:
Whole-cell TRPC6 currents were elicited in HEK293 cells using a voltage ramp protocol from -100 mV to +100 mV with a holding potential of -60 mV, 48 hours after transfection with
TRPC6 WT
or
A404V
cDNAs. The inward-current densities at -100 mV and the outward-current densities at +100 mV for
TRPC6 WT
and
A404V
variant were similar at baseline. However, after exposure to 50 μM 1-oleoyl acetyl-sn-glycerol (OAG, a TRPC6 activator), these current densities were significantly increased by 2.6-fold and 4.5-fold respectively in the
WT
(n=20 cells), and by 8.4-fold and 8.9-fold respectively in the
A404V
variant (n=12 cells, p<0.05 vs. WT). The OAG effects were abolished by superfusion with 1 μM BI-749327 (a specific TRPC6 inhibitor). Moreover, a 24-hour treatment with 0.5 μM doxorubicin (DOX) further amplified the effects of OAG, increasing the total inward- and outward-current densities by 7.2-fold and 9.5-fold respectively in
TRPC6 WT
(n=11 cells), and by 13.9-fold and 14.7-fold respectively in the
A404V
variant (n=13 cells, p<0.05 vs. WT). In comparison, the OAG effects on
TRPC6 WT
and
A404V
channels were not potentiated by treatment with 0.5 μM doxorubicinol (DOXol, a metabolite of DOX) for 24 h (n=10-12 cells, p=N.S.). Molecular docking studies showed that OAG had a lower binding energy (-5.60 kcal/mol) and a smaller apparent equilibrium constant (Kd) of 0.079 mM with the
A404V
variant, compared to those of -4.49 kcal/mol and 0.511 mM respectively with
TTRPC6 WT.

Conclusion:
TRPC6 A404V
is a gain-of-function variant with a higher binding affinity to OAG. Treatment with DOX but not DOXol greatly enhances
TRPC6 WT and A404V
channel activation by OAG. Thus, cancer patients carrying the
TRPC6 A404V
variant may be more vulnerable to develop HF upon treatment with anthracycline.
Abstract 4126692: Effect of change in different adiposity indices over 10 years on Incident Type 2 Diabetes: The UK Whitehall II Study
Authors: Huang Cunrong , Martin Peter , Chen Yuntao , Bann David , Britton Anne
Published: November 2024

Background:
It is accepted that obesity increases type 2 diabetes risk. Some studies have explored associations between changes in body mass index (BMI) or waist circumference (WC), 2 indicators commonly used to assess obesity, and diabetes risk separately. However, there are few studies on the effect of change in waist-to-height ratio (WHtR), an index that has been suggested to be more strongly associated with diabetes than BMI and WC, on incident diabetes. Even fewer studies simultaneously examined the associations of change rate in the 3 indices with diabetes.

Hypothesis:
WHtR change may be more strongly associated with diabetes than BMI and WC.

Aims:
This study aims to investigate the change rates of BMI, WC, and WHtR in the UK adult population, and compare the effects of different adiposity indices’ changes on diabetes development.

Methods:
To make facilitate quantitative comparison of BMI, WC and WHtR, we used their standardized values. Repeated measures of the 3 indices were obtained from Phase 3 (1991-94), 5 (1997-99), and 7 (2002-04) of the UK Whitehall II Study (included persons participated in at least 2 of the 3 visits). Mixed effects model was used to calculate individual change rate of the 3 indices. Non-diabetic participants at Phase 7 were then followed up for incident diabetes until Phase 9 (2007-09). We examined the prospective association between change rate of the 3 indicators and diabetes by Cox regression analysis.

Results:
A total of 5,539 persons were included (mean age at Phase 3 was 49.6 years, 28.8% women). All adiposity indicators increased during Phase 3-7. The overall change rate of WHtR (0.07 SD/year) was higher than BMI (0.04 SD/year) and WC (0.06 SD/year). There were 375 non-diabetic (Phase 7) participants developing diabetes after a median follow-up period of 5.0 years. Initial WC value (HR:1.56) and WHtR value (HR:1.50) showed a stronger association with diabetes than initial BMI (HR:1.27). When the 3 indices increased at the same rate, WC change (HR:3.83, 95% CI: 2.48-5.93) had a higher risk of developing diabetes than changes in WHtR (HR:3.19, 95% CI: 2.19-4.64) and BMI (HR:2.57, 95% CI: 1.85-3.56).

Conclusions:
The rate of increase over time was higher in WHtR than BMI and WC in this UK adult population. Increases in WC and WHtR were more strongly associated with incident diabetes than BMI. When the 3 indices increased at the same rate, change in WC increased a higher risk of developing diabetes relative to BMI and WHtR.
Abstract 4126731: Cumulative Cardiovascular Health in Young Adulthood and Systemic Target Organ Damage: The Coronary Artery Risk Development In Young Adults (CARDIA) Study
Authors: Guo James , Ning Hongyan , Liu Kiang , Wilkins John , Bhatt Ankeet , Lloyd-Jones Donald
Published: November 2024

Introduction:
Cardiovascular health (CVH) in young adulthood (YA) is strongly associated with subclinical and clinical outcomes in later life. Longitudinal patterns of CVH exposure through YA (e.g., cumulative CVH exposure) may be particularly important. However, no studies have assessed cumulative CVH in YA and its association with target organ damage (TOD).

Methods:
CVH was defined using Life’s Essential 8 (LE8) score. CARDIA participants (ppts) with CVH assessed at ≥3 exams over 20 years of follow-up in YA (year [Y]0 to Y20 exams; mean ages 25 to 45 years) were included. Cumulative LE8 scores (cumLE8; higher = better CVH over time) were calculated as the sum of LE8 scores through YA carried forward between exams measured as point*years. Eight markers of TOD (listed in Results) were measured at subsequent exams (Y20 or Y25) including cardiac, renal, pulmonary, and neurologic markers. Associations of cumLE8 with markers of TOD were assessed using partial effects regression models adjusted for race, sex, and maximal education.

Results:
There were 3,485 ppts (43.4% men, 46.2% Black) with mean cumLE8 score of 1,448.6 (SD 211.4) point*years. Higher cumLE8 in YA was linearly associated with lower measures of cardiac (left ventricular mass index, carotid intima media thickness, prevalence of coronary artery calcium), renal (estimated glomerular filtration rate [eGFR] in men), and neurologic damage (proportion of white matter hyperintensity on brain MRI) (
Figure
). Higher cumLE8 was also linearly associated with better lung function (forced expiratory volume in 1 second, forced vital capacity). Urine albumin-creatinine ratio (in men and women) and eGFR (in women) were non-linearly associated with cumLE8.

Conclusions:
Our findings underscore the importance of high cumLE8 in YA and its association with reduced onset of TOD later in life. Primordial prevention strategies are needed to achieve and maintain high CVH through the critical period of YA.
Abstract 4126895: Bridging the Gap in San Joaquin Valley LGBTQ+ Cardiovascular Disease and Mental Health Disparities
Authors: Siddiqui Maha
Published: November 2024

Introduction:
LGBTQ+ adults experience discrimination and violence that lead to stressors in daily life. Homophobia affects the mental health of the growing San Joaquin Valley (SJV) LGBTQ+ community leading to psychological distress and mental health concerns which can further lead to High Blood Pressure (HBP) and cardiovascular disease (CVD). SJV has a growing rate of LGBTQ+ migrants from the Bay Area who may be at risk for psychological distress and CVD. With a diverse community of low income and minority groups, the lack of physicians do not represent the workforce of SJV.

Objectives:
Trainees conducted Kessler psychological distress tests, HBP and CVD screenings across college campuses and community events to reduce the risk of CVD and spread awareness about mental health, CVD and its implications in the LGBTQ+ population due to environmental racism in the most underserved region for health care, SJV.

Methods:
I trained and provided mentorship to medically ambitious diverse low-income high school to instill a passion in them to come back after their medical education to practice medicine and promote LGBTQ+ health equity in SJV. Students conducted weekly Kessler psychological distress tests, HBP screenings and serve as a health technology coach. Each student monitored 2 hypertensive and psychological distressed patients. Kessler psychological distress tests and CVD screenings were conducted at college campuses to spread awareness about LGBTQ+ mental health and heart health and track psychological distress and HBP in the LGBTQ+ community.

Findings:
-About 88% (98 of 112) experienced some form of discrimination from a health care professional

-About 57% (64 of 112) of SJV LGBTQ+ population are at risk for CVD

-About 14% (16 of 112) of SJV LGBTQ+ population are Stage 1 hypertensive

-About 76% (83 of 112) of SJV LGBTQ+ population are at risk for hypertension and are psychologically distressed

Direct Outcomes:
-Youth learned the value of empathy and service to disadvantaged LGBTQ+ communities through the program and volunteering

-LGBTQ+ empowerment and students are determined to pursue medicine and address community concerns

-Awareness, education among LGBTQ+ community for better heart and mental health

-Better understanding in how to manage and seek referral for mental health and health systems concerns

-Students learned about SJV health disparities and applied precision medicine to their own health inequity projects in SJV

-Improved LGBTQ+ patient provider trust
Abstract 4126971: Advanced Care Planning in the CCU: What are the Numbers?
Authors: Sweeney Daniel , Uppal Priya , Jamrozik Thomas , Hutchison Paul
Published: November 2024

Introduction:
Advanced care planning (ACP) is an important, though often neglected, part of medicine. It can promote goal-concordant care and improve communication between the medical team and patient. This is especially important in the intensive care unit, where important health decisions are made by patients and families. Previous studies have shown that patients and families are interested in ACP discussions, especially in intensive care units. Studies are limited, however, in analyzing the prevalence of these discussions prior to and during admission to the cardiac intensive care unit (CCU).

Methods:
This was a retrospective cohort study. Baseline demographics were collected on patients admitted or transferred to the CCU between January 1, 2022- July 1, 2022. The presence of any ACP (documentation including POLST forms, advance directives, or power of attorney forms) filled out prior to and during admission was recorded. Length of stay, outcome of admission, discharge disposition, and baseline comorbidity index using the Charlson Comorbidity Index (CCI) were also recorded. Transplant patients, patients admitted for transplant, and patients who underwent multiple admissions were excluded from the study.

Results:
Between January and July, 400 patients met criteria for inclusion. The average age was 67, with males accounting for 62% of patients. The average CCI amongst these patients was 6.95. Of the 400 patients, 31 had ACP completed prior to their admission (7.75%). Out of the 369 patients who did not have ACP in place upon admission, 9 had ACP completed during their stay in the CCU (2.44%). There was no difference in CCU hours amongst those who had ACP prior to admission compared to those who did not (p=.9). There was, however, a difference among CCI index: those with ACP prior to admission had an average CCI of 9.94 compared to 6.7 in those without ACP (p<.001).

Conclusions:
Patients at risk of cardiac-related mortality can benefit from ACP discussions prior to the onset of critical illness; however, only a small fraction of patients admitted to the CCU have proper documentation of this process. Inpatient and outpatient ACP can target at-risk patients to improve both the conversation and documentation of patient values and treatment preferences. Possible interventions to provide this care include physician education, consistent discussion of ACP during rounds, or flagging patients without ACP in the EMR.
Abstract 4126987: A Case of Recurrent Neurocardiogenic Syncope in a COVID-19 Patient
Authors: Naeem Nauman , Sharif Muhammad Hammad , Osama Muhammad , Takla Andrew , Arora Sahej , Khan Ghazi , Rao Mohan
Published: November 2024

Background:
COVID-19 infection has been associated with a broad range of clinical manifestations. There are very few reported cases of COVID-19 patients presenting with syncope as an initial symptom. We present an extraordinary case of recurrent neurocardiogenic syncope in a COVID-19 patient.

Case:
A 66-year-old male presented after experiencing two episodes of syncope. He denied any prodromal or anginal symptoms. His medications included propranolol 10 mg twice daily for essential tremors. He had no family history of unexplained syncope or sudden cardiac death. He was hemodynamically stable and had one episode of fever at 102°F. Telemetry recording showed vagal-mediated sinus arrest and pauses without escape. Blood work showed normal cell counts, electrolytes, thyroid-stimulating hormone, and erythrocyte sedimentation rate, with a slightly elevated C-reactive protein of 22.2 mg/L. He tested positive for COVID-19 and had negative Lyme and Ehrlichia serologies.

Decision Making:
Due to symptomatic long sinus pauses, propranolol was discontinued, and he received a temporary pacemaker set at 50 beats per minute (bpm). He had another syncopal episode while being paced at 50 bpm, suggesting a neurocardiogenic mechanism, so the pacing rate was increased to 70 bpm. An echocardiogram showed a normal ejection fraction without any significant valvular disease. The syncope was determined to be vasovagal due to autonomic dysfunction in the setting of COVID-19. After 72 hours without further syncope, the temporary pacemaker was removed, and he was discharged home with an implantable loop recorder (ILR). A one-month follow-up showed no syncope, and ILR interrogation showed no bradycardia or pauses.

Conclusion:
Neurocardiogenic syncope with prolonged asystole and sinus pauses is an uncommon presentation of COVID-19 infection. The clinical course of autonomic dysfunction following COVID-19 is not very clear, and monitoring with an ILR is reasonable before considering permanent pacemaker implantation.
Abstract 4127417: Trends in Atherosclerotic Cardiovascular Disease Related Mortality Among Older Adults in the United States From 1999-2021
Authors: Siddiqi Ahmed , Maniya Muhammad Talha , Ali Kumail Mustafa , Salman Ali , Raja Adarsh , Khan Laibah , Siddiqi Tariq Jamal , Hall Michael
Published: November 2024

Background:
Atherosclerotic cardiovascular disease (ACVD) is the leading cause of mortality in the U.S, and increasing age is one of the greatest risk factors for the development and prognosis of ACVD. However, ACVD-related mortality trends in older adults have not yet been established.

Aims:
This study aims to highlight the annual trends and demographic differences in ACVD-related mortality among older adults in the U.S. from 1999 to 2021.

Methods:
The CDC WONDER multiple-cause of death database was examined from 1999 to 2021 for ACVD-related mortality in adults >65 years of age. Age-adjusted mortality rates (AAMRs) per 100,000 persons was calculated. Trends and annual percent changes (APCs) were calculated, and subsequently stratified by overall, sex, race/ethnicity, urbanization status, and census region.

Results:
Between 1999 and 2021, 9,307,495 ACVD-related deaths occurred among older adults in the U.S. AAMRs decreased from 1370.7 in 1999 to 803.5 in 2014 (APC, -3.64 [-3.89 to -3.46]), after which it gradually decreased to 741.3 in 2019 (APC, -1.24 [-2.54 to 0.19]), and then increased to 841.5 in 2021 (APC, 7.00 [3.92 to 9.18]). Men had consistently higher AAMRs than women from 1999 (AAMR men: 1754.1 vs women: 1122.2) to 2021 (AAMR men: 1169.6 vs women: 599.6). Non-Hispanic (NH) Black or African American older adults had the highest AAMR in 2020 (886.1), followed by NH White (849.4), NH American Indian/Alaska Native (752.5), Hispanics or Latino (718.3) and NH Asian or Pacific Islanders (494.4). AAMR also varied substantially by region (overall AAMR until 2020: Midwest 875.1; South 872.2; Northeast 801.0; West 789.2), and rural areas had higher ACVD-related mortality (993.5) than urban regions (954.7).
Figure 1.

Conclusion:
Following a progressive decrease until 2019, ACVD-related mortality in U.S. older adults demonstrated a sharp increase in mortality in 2020 and 2021. The highest AAMRs were observed among Black or African American adults and men, and among patients living in the Midwestern and non-metropolitan areas. A targeted approach, with tailored strategies is required to counter the recent surge in ACVD-related mortality in older adults in the U.S.
Abstract 4127562: Age, Adiposity-Related Anthropometrics, and Clinical Outcomes in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: A Participant-Level Pooled Analysis of Randomized Trials
Authors: Ostrominski John , Lassen Mats , Butt Jawad , Claggett Brian , Anand Inder , Desai Akshay , Jhund Pardeep , Lam Carolyn , Pfeffer Marc , Pitt Bertram , ZANNAD Faiez , Zile Michael , McMurray John , Solomon Scott , Vaduganathan Muthiah
Published: November 2024

Background:
Age has been shown to modify the population-level association between body mass index (BMI) and mortality. However, whether age modifies the association between adiposity-related anthropometrics and adverse outcomes in heart failure (HF) populations has not been systematically explored.

Methods:
In this participant-level pooled analysis of five international, multicenter, randomized-controlled trials enrolling adults with HF and either mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), the association between age and adiposity-related anthropometrics (BMI, waist circumference [WC], and waist-to-height ratio [WHtR]) and the primary composite outcome of time-to-first HF hospitalization or cardiovascular (CV) death was evaluated using multivariable adjusted Cox proportional hazards models (stratified by treatment and trial) and restricted cubic splines.

Results:
Among 21,606 participants in the analysis (mean age, 71±9 years; 49% female; 83% White; mean BMI, 30±6 kg/m
2
), 5,350 (25%) were aged <65 years, 8,273 (38%) were aged 65-74 years, and 7,983 (37%) were aged ≥75 years at baseline. Older individuals were more likely to be female, have lower BMI and WC, and higher left ventricular ejection fraction. Overall, BMI, WC, and WHtR were steeply and non-linearly associated with the primary outcome (
Figure
). Age, as either a categorical or continuous variable, significantly modified the covariate-adjusted association between all anthropometrics and the primary composite outcome (
P
≤0.001 for all) (
Figure
). A J-shaped relationship, characterized by higher incidence of the primary outcome with lower anthropometric values, was observed only for BMI and was substantially attenuated among younger adults. Irrespective of the anthropometric used, increasing adiposity was most steeply associated with primary events among adults aged <65 years.

Conclusions:
In this pooled analysis of HFmrEF/HFpEF trials, age was a powerful modifier of the relationship between excess adiposity and HF hospitalization or CV death. An “obesity-survival paradox” – observed only for BMI – was not apparent in younger participants, who exhibited the steepest increase in the rate of clinical events with higher adiposity.
Abstract 4127664: Influences of Age on Improvement of Health-Related Quality of Life in Patients with Atrial Fibrillation following Initial Treatment
Authors: Nakamaru Ryo , Ikemura Nobuhiro , Kohsaka Shun , Kimura Takehiro , Yoshinori Katsumata , Nishiyama Takahiko , Ueda Ikuko , Tanimoto Kojiro , Negishi Koji , Takatsuki Seiji , Spertus John , Ieda Masaki
Published: November 2024

Background:
The prevalence of Atrial Fibrillation (AF), the most cardiac common arrhythmia, increases with age. Various treatment strategies are available to improve health-related quality of life (HRQoL) in patients with AF; however, the impact of age on HRQoL treatment benefits is unknown.

Aims:
To investigate the association of age with HRQoL benefit across different treatment strategies.

Methods:
Using data from a multicenter registry for outpatients with early recognized AF, HRQoL at enrollment and 1 year later was measured with the Atrial Fibrillation Effect on Quality-of-life quesTionnaire (AFEQT). The association between age and the 1-year changes in AFEQT-overall summary (OS) and subdomain scores with either rate or rhythm control strategies were assessed using generalized additive models (GAM) to address non-linear relationships. To support clinical interpretation, multivariable linear regression models were performed with categories of age ranges.

Results:
Among 2786 patients (31.7% women, 54.7% rhythm control); 946 were <65 of age, 1019 were ≥65–75, and 821 were ≥75 years old. Rhythm (vs. rate) control was pursued in 76.6%, 58.0%, and 33.6% and mean AFEQT-OS changes were 11.1 (SD 16.6), 8.0 (17.0), and 4.7 (18.2) in those aged <65, 65–74, and ≥75, respectively. The GAM showed improvements in AFEQT-OS attenuated with advancing age with both treatment strategies (
Figure
). Linear regression analyses showed lesser improvements in AFEQT-OS as higher age categories (≥65–75 vs. <65, β -1.12 [95% CI, -2.33 – 0.09]; ≥75 vs. <65, β -3.86 [-5.29 – -2.42]), which were mainly driven by lesser improvement in AFEQT-daily activities scores, without differences in AFEQT scores for symptom or treatment concerns (
Table
).

Conclusions:
In AF patients, HRQoL benefits after treatment were attenuated by advancing age, primarily driven by less improvement in functional limitations, underscoring the need for further research to identify optimal treatment strategies for older adults.
Abstract 4127681: Neutrophil-lymphocyte ratio as a marker of cardiovascular outcomes in patients with chronic coronary syndrome
Authors: Trombini Pinesi Henrique , Moreira Eduardo , Barbosa Marcelo , Martins Eduardo , PITTA FABIO GRUNSPUN , Lima Eduardo , RACHED FABIANA HANNA , Serrano Carlos
Published: November 2024

Background:
Inflammation is one of the pathophysiological processes involved in the genesis and progression of atherosclerosis and has been increasingly used as a therapeutic target in recent years. The neutrophil-lymphocyte ratio (NLR) is a promptly accessible inflammatory biomarker strongly associated with prognosis in the acute coronary setting. However, there are few data in patients with chronic coronary syndrome (CCS).

Objective:
Analyze the association between NLR and cardiovascular outcomes in patients with CCS.

Methods:
Patients with CCS, defined as a previous revascularization procedure (surgical or percutaneous), previous myocardial infarction (MI) or stenosis > 50% in at least one epicardial coronary artery, were included and followed up on an outpatient basis. The NLR was calculated using the baseline blood count. The main outcome was the composite of death, non-fatal myocardial infarction and non-fatal stroke.

Results:
The study population consisted of 975 patients, with a median age of 65 years and 30% were women. Previous MI was present in 61%, 30% had undergone previous revascularization surgery and 46% had percutaneous coronary intervention. Diabetes was prevalent in 59% and hypertension in 95%. The median NLR was 2.15 (IQR 1.25 - 2.87). Patients with NLR ≥ 2.15, when compared to those with NLR < 2.15, presented more left ventricular (LV) dysfunction (58% vs. 55%; p=0.003) and lower LDL-C serum levels (81 vs. 88 mg/dL; p=0.004). There was no association between NLR and coronary anatomical severity. NLR correlated with age, LDL-C and LV function (p < 0.05 for all). During follow-up, 152 events of the composite primary outcome were registered, with an estimated 3-year incidence of 15.6% in the overall population – higher within patients with NLR ≥ 2.15 when compared to NLR < 2.15 (20% x 14%, p = 0.002), as shown in the figure. In the multivariate analysis, the 3rd quartile of NLR had a 31% higher risk than the 1st quartile (p < 0.05).

Conclusion:
In this study, the NLR, an easily available inflammatory biomarker, independently correlates with cardiovascular outcomes in a population with CCS.
Abstract 4127909: Smartphone-enabled, home-based exercise in patients with symptomatic peripheral arterial disease: the Smart Step Grady randomized trial
Authors: Mustapha Aishat , Chen Yunyun , Meer Madeline , Alrohaibani Alaaedin , Parrish Cate , Abdelhamid Smah , Minton Keri , Benarroch-Gampel Jaime , Ramos Christopher , Rajani Ravi , Wenger Nanette , Garcia-Toca Manuel , Shah Amit , Harzand Arash
Published: November 2024

Introduction:
About 10% of peripheral artery disease (PAD) patients develop claudication, with African Americans at higher risk and more severe symptoms. While supervised exercise therapy (SET) is a primary treatment, its uptake is low. We assessed the feasibility and effectiveness of smartphone-delivered home-based exercise therapy (HBET) in improving functional capacity and PAD symptoms in low-resource settings lacking SET.

Methods:
We conducted an interim analysis of Smart Step, a pilot randomized trial (1:1 ratio) comparing smartphone-enabled HBET to usual care (UC) in symptomatic PAD patients at Grady Memorial Hospital, a public safety net hospital in Atlanta, GA, from August 2018 to March 2024. The HBET group received virtual exercise coaching, app-based education, messaging, and reminders for 12 weeks. The primary outcome was the change in 6-minute walking distance (6MWD) at 12 weeks. Secondary outcomes included changes in the Walking Impairment Questionnaire (WIQ) and Short Form 36 (SF-36) scores. Data were analyzed using intention-to-treat, with mixed model repeated measures regression assessing the association between 6MWD and treatment.

Results:
We screened 102 patients and enrolled 46. To date, 26 (56%) participants have completed the study, 6 (13%) dropped out, and 14 (30%) are pending completion. The mean [SD] age was 63 [12] years, with 50% female and 90% African American. After 12 weeks, the mean 6MWD increased by 15.7 m from a baseline of 336.0 m in the HBET arm (n=13) and decreased by 6.6 from a baseline of 310.2 m in the UC arm (n=13). The between-group difference was 22.4 [95% CI -11.8 – 56.6] m; p=0.19). The WIQ stair climbing score changed by -10.9 in the UC arm vs. 7.1 in the HBET arm (between group difference 17.9 [95% CI 1.1-34.8]; p=0.04), while the other WIQ sub-scores were more similar between groups. The 12-week changes in SF-36 scores were not different by group.

Conclusion:
In this preliminary analysis, the HBET arm showed within-group improvements in 6MWD and symptoms after 12 weeks, but most changes were not significantly different when comparing them with the UC arm. Future analyses are pending and will provide the necessary statistical power for a more precise measure of the treatment effects.
Abstract 4127919: Disease-associated variants in
DSP
-encoded desmoplakin are common, yet low penetrant alleles associated with development of myocarditis and cardiomyopathy at a population level
Authors: Gurumoorthi Manasa , Sharaf Dabbagh Ghaith , Hesse Kerrick , Wolfe Rachel , Shah Ravi , Kurzlechner Leonie , Asatryan Babken , Chahal Anwar , Landstrom Andrew
Published: November 2024

Intro:
DSP-
encoded desmoplakin is implicated in a distinct form of arrhythmic cardiomyopathy (ACM), often involving the LV and characterized by myocardial inflammation. Conventional ACM diagnostic criteria has poor sensitivity for
DSP
-associated ACM, thus highlighting the need to identify the full spectrum of phenotypic risk associated with disease-associated
DSP
variants.

Objective:
To analyze the genotypic and phenotypic spectrum of
DSP
-mediated disease at a large population level.

Methods:
UK Biobank participants with exome sequencing (ES) were included. Variants were filtered by gene evidence category, yielding 3 groups: predicted deleterious (pDel); subset with predicted loss of function (LOF); and ultra-filtered subset by ClinVar 2* pathogenic/likely pathogenic (P/LP). Phenotypic penetrance was analyzed with
DSP
-neg individuals as control. Variant location analysis assessed LOFs by susceptibility to nonsense mediated decay region and missenses by amino acid sequence to identify mutational hotspots where P/LPs localize.

Results:
Out of 200,580 with ES, 1407
DSP
carriers had pDel, 168 with LOF, and 44 with ClinVar 2* P/LP.
DSP
carriers had higher burden of myocarditis, cardiomyopathy (CM), and heart failure. A progressive enrichment in myocarditis and CM was observed by more stringent variant filtering in
DSP
carriers compared to control. A higher proportion of
DSP
carriers had myocarditis – 0.28% (4) of the pDels, 1.8% (3) of LOFs, and 4.5% (2) compared to control 0.07% (p<0.05). A parallel trend noted the proportion of
DSP
carriers with CM growing from 1.4% (19) to 5.4% (9) and 6.8% (3) in the pDel, LOF, and ClinVar 2* P/LPs respectively compared to 0.6% in the control group (p<0.01). Location analysis of missense variants revealed that P/LPs localized in higher proportions (74%) to key domains compared to non-P/LPs (50%; p<0.001), highlighting prognostic value of predicting pathogenicity of missense
DSP
variants by mutation hotspots.

Conclusions:
While
DSP
variants are relatively common in the population, variant presence is associated with low penetrance. Enhancing clinical penetrance with increasingly stringent filtering of
DSP
variants emphasizes the importance of variant evaluation in clinical risk assessment. This first-in-kind population study of
DSP
provides insights into novel risk prediction factors, allowing us to predict pathogenicity by type and location of mutation and using variant filtering strategy to better assess phenotypic penetrance.
Abstract 4128261: Heart Failure-Associated Sudden Cardiac Death: Trends and Demographic Differences in the United States Adults, 1999 to 2020
Authors: Siddiqi Ahmed , Maniya Muhammad Talha , Dhaliwal Jasninder , Syed Saif , Mattumpuram Jishant , Yamani Naser , Vipparthy Sharath , Siddiqui Simra , Faisal Sarah , Siddiqi Tariq Jamal , Hall Michael
Published: November 2024

Background:
The US population has seen a dramatic increase in the burden of heart failure (HF) and sudden cardiac death (SCD) mortality. SCD is one of the prominent causes of mortality in HF patients. However, HF-associated SCD-related mortality trends have not been established yet.

Aims:
This study aims to highlight the annual trends and demographic differences in HF-associated SCD mortality among adults in the U.S from 1999-2020.

Methods:
The CDC WONDER multiple-cause of death database was examined from 1999 to 2020 for HF-associated SCD mortality in adults over the age of 25. Age-adjusted mortality rates (AAMRs) per 1,000,000 persons was calculated. Trends and annual percent changes (APCs) were assessed overall and stratified by sex, race/ethnicity, urbanization status, and census region.

Results:
Between 1999 and 2020, 39,660 HF-associated SCD-related deaths occurred among US populations. Following a reduction from 10.9 in 1999 to 6.8 in 2018 (APC, -2.5 [-2.8 to -2.3]), AAMR increased to 8.2 in 2020 (APC, 10.3 [3.6 to 13.7]) in the overall population. Men had consistently higher AAMRs than women from 1999 (AAMR men: 15.1 vs women: 7.9) to 2020 (AAMR men: 11.3 vs women: 5.6). Non-Hispanic (NH) Black or African Americans had the highest AAMR (14.0), followed by NH Whites (8.3), and Hispanics or Latinos (3.4). Southern region had the highest AAMR (10.4), followed by Midwest (9.6), West (5.8), and Northeast (5.8). Moreover, rural areas had consistently higher AAMR (14.6) than urban areas (6.9).

Conclusion:
Following a steady decline until 2018, HF-associated SCD mortality in adults increased between 2018 and 2020. The highest AAMRs were observed among Black or African American adults and men, and patients living in the Southern and non-metropolitan areas. Tailored strategies focusing specifically on arrhythmic events and related mortality in HF patients are needed to address the recent surge in mortality rates among these demographics.
Abstract 4128352: Association Between G6PD Deficiency and Congenital Heart Disease Incidence and Hospital Outcomes
Authors: Hendrickson Alana , Caryl Natalie , Meziab Omar , Andrews Jennifer , barber brent , Seckeler Michael
Published: November 2024

Background:
G6PD deficiency classically presents with hemolytic anemia, but associations have been described with atherogenesis and coronary artery disease. There are limited data that also suggest a link between G6PD deficiency and the development of congenital heart disease (CHD).

Hypothesis:
We hypothesize a higher incidence of CHD among individuals with G6PD deficiency as well as worse hospital outcomes for those with CHD and G6PD deficiency.

Methods:
We reviewed the Vizient® Clinical Data Base (a national, administrative database) from 10/2019-3/2024 for admissions of individuals aged 0-25 years with ICD-10 codes for moderate to severe CHD with and without and G6PD deficiency (D55.0, D75.A) to calculate and compare CHD incidence. Additional data included: demographics, hospital outcomes and costs. Hospital outcomes were compared using t-tests for normally distributed data, Mann-Whitney U test for non-normally distributed data and χ
2
for categorical data.

Results:
There were 213,708 admissions of individuals with CHD and <1% had G6PD deficiency; findings in Table 1. Of the 6,363 admissions with G6PD, 289 (4.5%) had CHD and of 11,179,670 without G6PD, 213,419 (1.9%) had CHD (
p
<0.001). Patients with CHD and G6PD deficiency had male predominance and more Blacks (consistent with known G6PD deficiency epidemiology), longer length of stay and higher hospital costs than those without G6PD deficiency (Table 1).

Conclusions:
This review of a national database shows a higher incidence of CHD in admissions with G6PD deficiency as well as worse hospital outcomes (longer length of stay, higher costs) for those with CHD and comorbid G6PD deficiency. There were demographic differences, but these reflect the typical inheritance of G6PD deficiency. While there may be potential interplay between race/ethnicity and these outcomes as well, further investigation is needed.
Abstract 4128526: Brain Natriuretic Peptide is Not Predictive of Days Alive and Out of Hospital During the Interstage Period in Infants with Hypoplastic Left Heart Syndrome
Authors: Schwartz Ilana , Leonard Jan , Zavez Alexis , Essaid Luma , Stagg Alyson , Ravishankar Chitra , Giglia Therese , Gardner Monique , Shustak Rachel
Published: November 2024

Background:
Infants with hypoplastic left heart syndrome (HLHS) have the highest risk of morbidity and mortality during the interstage period. Brain natriuretic peptide (BNP) is frequently measured during the Stage I palliation (S1P) hospitalization. However, there is limited data on the association of BNP with interstage morbidity and mortality. In this context, we sought to examine the association between maximum BNP during the S1P hospitalization and last BNP prior to S1P discharge with days alive and out of hospital (DAOH) during the interstage period. We hypothesized that patients with higher BNPs during their S1P hospitalization would have fewer DAOH during the interstage period.

Methods:
We performed a single-center retrospective cohort study of infants with HLHS who underwent S1P at our institution between December 1, 2010 and December 31, 2022. Subjects were categorized based on maximum BNP and pre-discharge BNP tertiles. DAOH was calculated by subtracting the number of days hospitalized from the number of days alive during the interstage period. Multivariable zero-truncated negative binomial regression models were used to examine whether there was an association between BNP and DAOH. Models were adjusted for demographic, operative, and discharge characteristics and included an offset for interstage duration.

Results:
Of 251 infants, 221 (88%) had at least one BNP measured during their S1P hospitalization. The median maximum BNP was 529 (289-944) pg/mL, pre-discharge BNP was 346 (216-589) pg/mL, and DAOH was 97 (89-100) per 100 interstage days. The median maximum BNP in patients who remained admitted during the interstage period (n=32) was 1,027 (446-1,968) pg/mL which was significantly higher than the study cohort (p<0.001). Patients in the maximum BNP upper tertile were more likely to have moderate to severe atrioventricular valve regurgitation (p=0.04) and had higher pre-discharge and pre-Stage 2 palliation BNPs (p<0.001). There was no association between either maximum BNP or pre-discharge BNP with DAOH. Patients in the maximum BNP upper tertile had significantly more BNPs collected during their S1P hospitalization and interstage period.

Conclusions:
BNP during the S1P hospitalization is not predictive of interstage DAOH. In patients deemed candidates for discharge after S1P, repeated BNP measurements may have limited utility. Further work is needed to assess the association between BNP measured in the interstage period and longer-term outcomes.