bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13760: Long-Term Cancer Risk After Acute Coronary Syndrome in Selected Urban and Rural Areas. The ABC-7b* Study on Heart Disease
Authors: Mahmoud Heba T , Palmieri Rosa , Cordiano Rocco , Cavuto Fiorella , Pasquinucci Mattia , mahmoud moemen mohammed , Bagato Francesco , Berton Giuseppe S
Published: June 2023

Background
Increased cancer risk has been reported in patients with acute coronary syndrome (ACS). We attempted to investigate the geographic differences in this risk.

Methods:
In this prospective study, we enrolled 525 ACS patients admitted to 3 hospitals in Veneto region of Italy and discharged alive and free from neoplasia. Patients’ residency was classified into 2 urban and 2 nearby rural areas. We report the risk of neoplasia associated with smoking as a comparison.

Results:
With 3 exceptions, all patients completed a 24-year follow-up unless pre-empted by death. Urban (46%) and rural (54%) residents shared most of their baseline demographic and clinical characteristics. During the follow-up period, which represented 5851 person-years, 114 (22%) patients developed cancer. The cancer incidence rate was 17 and 22 per1000 person-years for urban and rural areas, respectively. No difference in cancer onset risk was found between urban and rural areas or between southern and northern provinces (HR 1.3; 95%CI 0.9–1.9;
p
= 0.21 and HR 1.4; 95% CI 0.9–2.0;
p
= 0.08, respectively) according to the unadjusted Cox regression analysis. Geographic areas, however, showed a strong positive interaction, with risk increasing from the urban to rural areas from southern to northern provinces (HR 2.9; 95% CI 1.3–6.5;
p
= 0.01). The fully adjusted model provided similar results. The HR for malignancy onset after ACS by smoking habit was (1.3; 95% CI 0.8–2.0;
p
= 0.26) in the unadjusted Cox regression model.

Conclusion
The present prospective study shows that the cancer onset risk among unselected ACS patients in Italy’s Veneto region significantly differs by geography with the northern rural area having the highest risk. The risk seems to be higher than that observed with smoking habits.

Figure 1. Graphical representation of the interaction analysis.
Abstract 13766: Delays in Care and Outcomes in Out-of-Hospital Cardiac Arrest With Shockable Rhythm
Authors: Wheelock Kevin M , Miller Elliott , Khera Rohan
Published: June 2023

Introduction:
Longer duration of ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT) is associated with worse outcomes among cardiac arrest patients. The ROC-ALPS trial randomized adults with shock-refractory VF or pVT to receive amiodarone, lidocaine, or placebo and found no difference in outcomes with either amiodarone or lidocaine. We sought to quantify the delay in drug administration and its effect on outcomes.

Methods:
We performed a retrospective analysis of the ROC-ALPS trial dataset. We included all patients who achieved return of spontaneous circulation (ROSC), had documented time to first shock, and time to trial drug administration. A logistic regression model was created with the time to drug administration after first shock, time to first shock, time to ROSC, study randomization arm, and other covariates, as a predictor of survival and neurologic disability (Modified Rankin Scale >=4) at hospital discharge.

Results:
A total of 1439 patients (1116 male, mean age 63.5 [SD 13.9] years) were included, with 1043 (72.5%) of arrests witnessed. The median (IQR) time to first shock was 9.5 (7.8 - 11.6) minutes, and patients received a median of 4 (3 - 7) shocks. The median time from first shock to study drug administration was 6.9 (4.4 - 10.5) minutes. Three hundred and nine (21.5%) patients received the trial drug within 4 minutes of first shock, 540 (37.5%) had delay of 4 - 8 minutes, 309 (21.5%) had delay of 8 - 12 minutes, and 281 (19.5%) had delay of > 12 minutes. Delay in trial drug administration of greater than 12 minutes from first shock was associated with worse survival and neurologic function at hospital discharge (
Table
). This effect was not modified by drug randomization group.

Conclusion:
Among out-of-hospital cardiac arrest patients with shock-refractory VF or pVT who achieved ROSC, there was an association between delayed medication administration, a measurable surrogate for overall delays in care, and worse outcomes.
Abstract 13780: Sociodemographic Differences in Patient Portal Research Recruitment of Older Adults With Heart Failure
Authors: Degroot Lyndsay , Miller Hailey , Pavlovic Noelle , Peeler Anna , Gilotra Nisha A , Davidson Patricia , Perrin Nancy , Szanton Sarah , Dy Sydney , Abshire Martha
Published: June 2023

Introduction:
Innovative recruitment strategies such as patient portal messaging (PPM) hold promise for high yield, low-cost recruitment of heart failure (HF) patients for research studies but may impact the diversity of the sample. We aimed to examine strategies used to recruit older adults with advanced HF during COVID-19 in an ongoing prospective palliative care research study.

Methods:
We used three recruitment strategies including the traditional in-person HF clinic screening or provider referral, and a more innovative direct-to-patient recruitment approach using EHR patient portal messaging (PPM) or email. We compared characteristics of participants recruited via PPM/email and traditional in-person recruitment strategies using chi-squared and t-tests. We used multiple logistic regression to examine associations between participant characteristics and recruitment type.

Results:
Most participants were recruited through PPM or email (86%, n=247) over 10 months and the remaining participants were recruited through provider referral or in-person recruitment at the heart failure clinic over 6 months (14%, n=40). Among our sample of 287 participants, 67% (n=201) were White, 28% (n=84) were Black, and the remaining 5% (n=13) were Asian, American Indian, or Alaska Native or identify with a non-listed race. The mean age was 68 years old. There was no significant difference in recruitment type by age, gender, or financial strain. There was a significant difference in recruitment type by race and education level. In a multiple logistic regression adjusting for age, gender, and financial strain, Black participants had a lower odds of PPM recruitment than white participants (OR 0.15, p<0.001). Additionally, those with higher education showed higher odds of PPM/email recruitment (OR 4.2 p = 0.001).

Conclusions:
In this study, PPM was an efficient recruitment strategy with higher odds of recruiting participants of White race and higher education compared to traditional recruitment strategies. Use of both traditional and more innovative direct-to-patient recruitment strategies may promote a more diverse study sample.
Abstract 13781: Same-Day Discharge After Transcatheter Mitral Valve Repair: Propensity Score-Matched Analysis From the Nationwide Readmissions Database 2014-2019
Authors: Goel Akshay , Malik Aaqib H , Bandyopadhyay Dhrubajyoti , Gupta Rahul , Hajra Adrija , Aronow Wilbert S , AHMAD HASAN
Published: June 2023

Introduction:
Transcatheter mitral valve repair (TMVR) has evolved over the years, and early discharge strategies are being increasingly adopted. However, there is paucity of data on the outcomes and safety of same-day discharge (SDD) after TMVR.

Methods:
Data from the Nationwide Readmissions Database 2014 to 2019 were analyzed. International Classification of Diseases codes were used to identify adult patients admitted for elective TMVR. Patients who underwent uncomplicated TMVR were identified by excluding patients with periprocedural complications such as bleeding, vascular access site complications, pericardial complications, stroke, myocardial infarction, shock, or death before discharge. A 1:3 propensity score-matched analysis was performed to compare outcomes of patients undergoing SDD and different-day discharge (DDD). The primary outcome of interest was the 30-day unplanned readmission rate.

Results:
We identified 34,683 patients who received complication-free TMVR, of which 232 (0.67%) underwent SDD. There was a gradually rising trend of SDD after TMVR over the study period. The baseline characteristics of the unmatched and propensity-matched SDD and DDD groups are shown. Patients in SDD group did not have a significantly higher 30-day readmission rate (15.7% vs 14.8%, p = 0.82) compared to DDD group, but had significantly lower mean hospitalization costs ($33,060 vs $41,134, p <0.001). Female gender, diabetes, chronic kidney or pulmonary disease, anemia, liver disease, cancer and atrial fibrillation were found to be independent predictors of 30-day readmissions after TMVR (shown in figure).

Conclusions:
Patients receiving a complication-free TMVR who were discharged on the same day as the procedure had a similar 30-day unplanned readmission rate compared with those that stayed in the hospital longer. Our findings suggest that same-day discharge after uncomplicated TMVR may be a safe and cost-effective strategy in selected patients.
Abstract 13807: Sex Differences in Patients Characteristics, Risk Factors, and Symptomatology in Older Adults With Pulmonary Embolism: Findings From the SERIOUS-PE Study
Authors: Bikdeli Behnood , Jimenez David , Piazza Gregory , Muriel Alfonso , wang yun , Khairani Candrika D , Rosovsky Rachel , Madridano Olga , Lopez-Saez Juan Bosco , Mellado Meritxell , Diaz Brasero Ana María , Mehdipoor Ghazaleh , O'Donoghue Michelle , Spagnolo Primavera A , Lu Yuan , BERTOLETTI Laurent , Lopez-Jimenez Luciano , Nunez-Fernandez Manuel J , Blanco-Molina Angeles , Bates Shannon , Gerhard-Herman Marie , Goldhaber Samuel , Monreal Manuel , Krumholz Harlan M
Published: June 2023

Background:
Biological sex is linked with pulmonary embolism (PE) disease presentation in young patients, such as the risk incurred by pregnancy. Whether sex differences exist in PE presentation, co-morbidities, risk factors, and symptomatology in older adults, the age group in which most of these events occur, remains unknown.

Methods:
We identified older adults (aged ≥65 years) with PE in a large international PE registry that is replete with granular clinical information about clinical characteristics and PE symptoms (RIETE registry, 2001-2021). To provide national data from the USA, we assessed sex differences in risk factors and clinical characteristics of US Medicare beneficiaries with PE (2001-2019).

Results:
The majority of older adults with PE in RIETE (19,294/ 33,462, 57.7%) and in Medicare database (551,492/ 948,823, 58.7%) were women (Panel A). Compared with men, women with PE less frequently had atherosclerotic diseases, obstructive lung disease, cancer, or unprovoked PE, but more frequently had a varicose veins, depression, prolonged immobility, or history of hormonal therapy (P<0.001 for all, Panel B). Compared with men, women less often presented with chest pain (37.3% vs 40.6%) or with hemoptysis (2.4% vs 5.6%), but more often presented with dyspnea (84.6% vs 80.9%) (P<0.001 for all). The proportions of patients with syncope (16.4% vs 15.9%) and patients with simplified Pulmonary Embolism Severity Index >0 (76.3% vs 75.0%) were comparable.

Conclusions:
In routine practice, elderly women constitute the largest proportion of patients with PE. Sex differences exist in risk factors and clinical presentation of older adults with PE, with cancer and cardiovascular disease being more common in men; and transient provoking factors such as immobility or hormone therapy being more common in women. Whether such differences correlate with disparities in treatment, or differences in short- or long-term clinical outcomes warrant further investigation.
Abstract 13813: Novel Noncoding Y RNA Drug Attenuates Fibrosis and Diastolic Dysfunction in Systemic Sclerosis
Authors: Jones Xaviar M , Ciullo Alessandra , Mesquita Thassio , Li Liang , Fournier Mario , Liu Weixin , Ibrahim Ahmed G , Marban Eduardo
Published: June 2023

Introduction:
Scleroderma is an autoimmune disease characterized by early vasculopathy, and fibrosis of the skin, heart and lung, resulting in irreversible scarring and organ failure. Current therapy only mitigates symptoms with no available curative options. We have previously demonstrated anti fibrotic and anti-inflammatory properties of EV-YF1, a small Y RNA abundant in extracellular vesicles secreted by cardiosphere-derived cells. Here we describe the therapeutic bioactivity of a shorter, engineered derivative, TY4.

Methods:
TY4, a 24-nucleotide chemically-modified oligonucleotide bioinspired by EV-YF1, was synthesized and packaged into lipid nanoparticles. To create a model of systemic sclerosis, C57BL/6J wild type mice (n=100 total) were injected with 100 μL bleomycin or PBS (control) subcutaneously every other day for 3 weeks. Animals then received either vehicle (0.9% NaCl), TY4 scrambled (as an RNA control) or TY4 via oral gavage. Endpoints include body weight, exercise capacity, echocardiography, and histologic quantification of fibrosis in heart and skin.

Results:
At study endpoint, animals receiving TY4 demonstrated body weight recovery (p<0.0001) and augmented exercise capacity (p<0.0002) compared to vehicle and TY4 scrambled. Similarly, cardiac fibrosis (p<0.0001) and dermal thickness (TY4 287 ± 45 μm, TY4 scrambled 426 ±75 μm , vehicle 419 ±116 μm p<0.0001) were largely normalized after TY4 administration. Diastolic dysfunction, as measured by echocardiography (E/E’), was present in controls but reverted to normal after TY4 administration (p<0.0001).

Conclusions:
These results demonstrate the therapeutic bioactivity of a bioinspired new chemical entity with the potential to become a synthetic, off-the-shelf drug for systemic sclerosis.
Abstract 13817: Diabetes Prevalence, Screening, Diagnosis, Treatment and Control in India: A Cross-Sectional Study of Individuals Aged 18 Years and Older
Authors: Varghese Jithin Sam , Ali Mohammed K
Published: June 2023

Previous studies from India reported management of diabetes (diagnosed: 53%, treated: 41%) among adults 15-49 years, a fraction of those suffering from disease. This study aimed to provide nationally-representative estimates of (i) the proportion of all adults (18+ years) with prediabetes and diabetes mellitus (DM), and (ii) the heterogeneity in their cascade of care by natal sex, age, and urbanicity.

Methods:
Using data from non-pregnant women (n = 959,468) and men (n = 935,829) in the National Family Health Survey-V (2019-21), we estimated the sex-specific prevalence of prediabetes and DM (see footnotes of
Figure
), and among adults with diabetes, the self-reported care cascade (ever screened, diagnosed, taking medication, under control defined by normoglycemia). All estimates incorporated the complex survey design and were stratified by urban versus rural or by age group (18-39, 40-64, 65+).

Results:
Nationally, the prevalence of prediabetes and DM were 11.3% (95%CI: 11.1,11.4) and 6.5% (95%CI: 6.4, 6.6) respectively. Prediabetes was similar in urban areas (vs rural areas) among men (%; 12.9 vs 12.0) and women (%; 11.1 vs 10.1). DM was higher in urban areas (vs rural areas) among men (%; 8.8 vs 5.6) and women (9.0 vs 5.3). Both prediabetes and DM were higher with increasing age. Screening in the total population was 30%, and was higher in urban areas, among women and higher with age. Among those with DM, only 72%, 51%, and 29% reported being diagnosed, taking medication, and under control, respectively. Diagnosis, treatment and control were also higher in urban areas, women, and older age groups (
Figure
).

Conclusions:
Despite the high prevalence of diabetes, there is a high unmet need in screening, diagnosis, treatment and control of disease nationally, and this is pronounced in rural adults. Moreover, the prevalence of prediabetes is high in rural areas, and those under 40 years, requiring a comprehensive approach for prevention and management.
Abstract 13819: Case Report of a Mitral Stenosis in a Young Growing Teenager After Rheumatic Mitral Regurgitation Valve Repair
Authors: Ngardig Ngaba Neguemadji , Chibuzo Uzoego N , Patel Meet , Gulati Amit , Khan Imteyaz A , Succès Allarangué , Lesbre Jean Philippe
Published: June 2023

Background:
Mitral stenosis (MS) is a well- defined slowly progressive complication after mitral valve repair for non-rheumatic mitral regurgitation (MR) in adults. The pubertal growth spurt has potential hemodynamic implications for a mitral valve prosthesis matched prior to surgery for a projected indexed effective orifice area (EOA) using the lower pre-surgical body surface area (BSA) that preceded the growth spurt. The peak height velocity usually occurs at Tanner stage 3 in females and 4 in males. To our knowledge, there are no reports highlighting a rapid increase in Trans-Mitral pressure gradient (TMPG) and decline in mitral valve area (MVA) after rheumatic MR valve repair in an early pubescent child. Case presentation: A 14-year-old female presented with orthopnea, abdominal distension and bilateral lower limb edema. She was cachectic with a BMI (Body Mass Index) in the first percentile, a high-pitched holosystolic murmur most prominent at the cardiac apex, bilateral basal crackles, tender hepatomegaly, pitting pedal edema and jugular venous distension. Her Tanner’s stage was 2. Anti-streptolysin O (ASO) titer was elevated. The transthoracic echocardiography (TTE) revealed loss of the mitral valve central coaptation with leaflet restriction and MR. There was an annular dilatation of the Tricuspid valve and Tricuspid regurgitation (TR). She had AHA/ACC stage D mitral and tricuspid regurgitation. Tricuspid annuloplasty and mitral valve repair for rheumatic MR were respectively performed utilizing Carpentier Edward numbers 30 and 34, appropriate for her pre-surgical BSA. Following the surgery, the murmur of MR resolved and her MVA was 4cm
2
. In the first year after surgery, she attained Tanner’s stage 3, a peak growth velocity of 8.4 cm during that year and her BMI rapidly increased to the 10th percentile. However, towards the end of the year she developed progressive increase in TMPG and a decline in the mitral valve area to 1.2 cm
2
.

Conclusion:
Growth spurts during puberty can potentially affect MR repair as the Mitral valve prosthesis based on a preoperative BSA is outgrown. There is a need for research for planning, prognostication and development of an optimal, individualized and adaptable approach to MR intervention in early pubescence.
Abstract 13823: Impact of Obesity on Inpatient Mortality and Adverse Cardiovascular Events in Patients With Cannabis Use Disorder: A Population-Based Analysis in the United States
Authors: Desai Rupak , Mondal Avilash , Devakumar Sahana , Gara Sirisha K , ODUGBEMI OLUFEMI , Jitta Sahas Reddy , Kodali lakshmi Spurthi , Yalla Naga Amrutha Sai , Juveria Fnu , Li Aobo , Bambhroliya Zarna , Vyas Ankit
Published: June 2023

Background:
Cannabis use disorder (CUD) is growing more prevalent, particularly among the young, and has the potential to increase cardiac/ cerebrovascular disease risk. We sought to determine how obesity affects cardiovascular outcomes in young cannabis users.

Methods:
Using 2019's National Inpatient Sample and relevant ICD-10 codes, we identified and compared young (18-44 years) obese vs. non-obese patients hospitalized with CUD. The risks of all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE- all-cause mortality, AMI, cardiac arrest, and stroke) and sex/racial disparities were assessed in young CUD admissions with and without obesity after adjusting for confounders

Results:
Overall prevalence of obesity among the young CUD cohort (n:539125, Mean age 30 years) was 10.3 % (55725/ 539125). The obese cohort was relatively older (mean age 32 vs 30 years) and often had females (58.6 vs 42.2%), blacks (33.6 vs. 23.1%), patients from the lowest income quartile (0-25th) (43.2 vs 39.7%), western hospitals (23 vs 20.1%) with lower non-elective admissions (85.3 vs 88.2%). Hypertension, diabetes, hyperlipidemia, PVD, prior MI, TIA/Stroke were more frequently seen in the CUD-Obese cohort. The young obese cohort with CUD had significantly higher adjusted odds of MACCE (aOR1.41, 95%CI 1.25-1.60, p<0.001) even after controlling other confounders. Males (aOR 1.63, 95%CI 1.39-1.90, p<0.001) but not females, whites (aOR 1.56, 95%CI 1.29-1.89, p<0.001) and blacks (aOR 1.30, 95%CI 1.06-1.58, p=0.011) with obesity had a higher risk of MACCE vs. the non-obese cohort. However, all-cause mortality was not found to be significantly higher in the young obese cohort with CUD (aOR 1.14 95%CI 0.80-1.63, p=0.473)
[Table 1]
.

Conclusions:
Obese cannabis users are 41% more likely to have a MACCE event during hospitalizations. Prospective studies are needed to examine cardiovascular consequences in cannabis users with established CVD risk factors.
Abstract 13828: Improvement in Racial Disparities in Heart Transplantation Following the Heart Allocation Policy Change
Authors: Sherard Curry , Skidmore Savannah , Shorbaji Khaled , Welch Brett , Kilic Arman
Published: June 2023

Objectives
Heart allocation policy (HAP) in the US was changed in October 2018. The aim of this study was to assess the effect of the new policy on racial disparities in heart transplantation (HT) outcomes.

Methods:
The United Network for Organ Sharing (UNOS) registry was used to identify adult patients undergoing isolated HT between 2010-2021. Patients were stratified into pre-HAP (January 2010 to September 2018) vs. post-HAP (October 2018 to September 2021). Recipient race was classified as White, Black, Hispanic, or Other. The primary outcome was post-HT mortality. Cox proportional hazard models were used for risk-adjustment in evaluating the independent effect of race on mortality.

Results
A total of 27,403 patients underwent HT in 143 centers during the study period. The proportion of non-whites undergoing HT increased in the post-HAP era: (pre-HAP: White 66.0%, Black 21.2%, Hispanic 8.2%, Other 4.6% versus post-HAP: White 62.5%, Black 23.2%, Hispanic 9.5%, Other 4.8%; p<0.001). In risk-adjusted analysis, Black recipients were at higher risk of post-HT mortality in the pre-HAP era (HR 1.31, 95% CI 1.22-1.41; p<0.001) but not in the post-HAP era (HR 1.12, 95% CI 0.03-1.34; p=0.222) compared to White recipients. Other non-white recipients had comparable risk-adjusted post-HT mortality rates compared to White recipients both in the pre- and post-HAP eras.

Conclusions:
Under the new heart allocation system, a higher percentage of recipients are non-white. In addition, racial disparities in outcomes have improved with Black recipients no longer having an increased adjusted risk of mortality following HT.
Abstract 13840: Impact of Age and Variant on Cardiovascular Events Among Patients Hospitalized With COVID-19: An Analysis From the AHA COVID-19 CVD Registry
Authors: Srivastava Pratyaksh K , Klomhaus Alexandra M , Tehrani David M , Ziaeian Boback , Rafique Asim , Desai Pooja S , Fonarow Gregg C , De Lemos James A , Parikh Rushi , Yang Eric H
Published: June 2023

Introduction:
The COVID-19 pandemic has caused significant cardiovascular (CV) morbidity and mortality. Using a national registry, we evaluate the impact of age and variant on CV outcomes across the three main coronavirus waves.

Methods:
Using the AHA’s COVID-19 CV Disease Registry, we divided patients hospitalized with COVID-19 into three groups based on dominant variant at the time of admission (Alpha, Delta, Omicron). We further stratified patients based on age (young: 18-40, older: >40 years). Using adjusted logistic regression, we compared rates of major adverse cardiovascular events (MACE: new onset heart failure, myocardial infarction, stroke, or death) and in-patient mortality between the groups.

Results:
There were 41,426 patients in the alpha wave (young: 5,585, older: 35,841), 3,349 patients in the delta wave (young: 690, older: 2,659), and 646 patients in the omicron wave (young: 213, older: 433). The cohort’s median (25
th
-75
th
%ile) age was 63 (50-75) years. 46.8% of the patients were female. Rates of MACE in the Alpha, Delta, and Omicron waves were 20.8%, 23.6%, and 15.5%. Rates of death were 14.0%, 14.8% and 6.0%, respectively. Compared to alpha, patients presenting during delta had increased odds of MACE and death (OR: 1.57 [1.42-1.73] and OR: 1.49 [1.34-1.66]). Patients presenting during omicron had decreased odds of death (OR: 0.6 [0.43-0.84]) and similar odds of MACE compared to alpha. When stratifying by age, both young and older patients presenting during delta had increased odds of MACE and death when compared to alpha (Fig 1A). When compared to young patients, older patients had increased odds of MACE in all three waves (Fig 1B).

Conclusions:
Patients had increased odds of MACE and death during delta compared to alpha. Compared to young patients, older patients had increased odds of MACE across all three waves. These findings help elucidate the differential impact of age and variant on cardiovascular outcomes among those hospitalized with COVID-19.
Abstract 13856: Ventricular Remodeling and the Effect of Continuous Positive Airway Pressure in Patients With Combined Diabetes Mellitus and Obstructive Sleep Apnea: A Secondary Analysis of a Randomized Clinical Trial
Authors: Silva Thiago Q , Bakker Jessie , Baltzis Dimitrios , Chan Raymond H , Manning Warren J , Wallace Meredith , Gongora Carlos A , Gilman Hannah , Sama Supraja , Nikolaidou Sofia , Sposito Andrei , Coelho-filho Otavio R , Hudson Margo , Jerosch-Herold Michael , Veves Aristidis , Malhotra Atul , Patel Sanjay , Neilan Tomas G
Published: June 2023

Introduction:
Type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are independently associated with adverse left (LV) and right (RV) ventricular remodeling. However, the effect of continuous positive airway pressure (CPAP) is unknown.

Hypothesis:
CPAP prevents adverse remodeling in T2DM+OSA overlap.

Methods:
In this prospective study, 141 participants (Control: 28; T2DM only: 27; OSA only: 29; T2DM+OSA: 57) were recruited and underwent home sleep testing and cardiac magnetic resonance. Subsequently, 53 adults from the T2DM+OSA group were enrolled in a 3-month, parallel-arm, randomized, placebo-controlled trial comparing active and sham CPAP. The measures of interest were LV and RV remodeling indices (mass/volume). Kruskal-Wallis for multiple groups and Wilcoxon rank-sum and signed-rank tests for paired samples for two groups were applied.

Results:
Groups were of similar sex [Control (males): 54%; T2DM: 44%; OSA only: 52%; T2DM+OSA: 65%; p=0.31)]; OSA and T2DM+OSA participants were older (age in years: 46± 15; 51±7.8; 53±10; 56±9.1*
#
; respectively p=0.001; *p<0.05 vs. control,
#
p<0.05 vs. T2DM only) and had higher BMI (29.8±6.3; 31±4.8; 34±6.3*; 35.2±6.6*
#
kg/m
2
, respectively p=0.001). At baseline, LV remodeling index (g/ml) was higher in T2DM+OSA (0.67±0.12; 0.71±0.10; 0.75±0.13; 0.78±0.16*; respectively, p=0.01), whereas RV remodeling index was similar (0.19±0.03; 0.20±0.03; 0.20±0.03; 0.21±0.04; p=0.33). The difference in LV remodeling index persisted after adjustment for age, sex and BMI (p<0.001). CPAP treatment over 3 months prevented progression of adverse LV remodeling compared with sham [difference: CPAP: -0.01 (-0.08, 0.08) g/ml; sham: 0.11 (-0.03, 0.17) g/ml; p=0.03)] but not of RV remodeling index [difference: CPAP: 0.01 (-0.04, 0.08) g/ml; sham: 0.003 (-0.02, 0.04) g/ml; p=0.82)].

Conclusion:
T2DM and OSA increased adverse LV but not RV remodeling. CPAP prevented the progression of adverse LV but not RV remodeling.
Abstract 13860: Heart Failure With Preserved Ejection Fraction Induced by Amyloid Light Chain Amyloidosis: A Case Report
Authors: Fondeur Acosta Juan R , Reyes Danna , Ramirez Annie Gisselle
Published: June 2023

Introduction:
Cardiac amyloidosis is a clinical disorder defined as an extracellular deposition of protein in the heart. Typically, signs and symptoms of heart failure develop in the advanced disease. High index of suspicion is required for the diagnosis of this disorder.

Results:
A 62 years old male came to the cardiology clinic due to lower extremity edema, fatigue, dyspnea on exertion. He had a 3 month history of progressive lower leg edema. On physical examination he had a positive S4; lung sounds were diminished and there was dullness to percussion over the lower two thirds; and bilateral lower extremity edema. Hospital admission was decided for management of decompensated heart failure. On admission, the surface ECG showed normal sinus rhythm with low QRS voltage in the limb leads, a RBBB and LPFB. Initial laboratory reported elevated NT-proBNP: 13,816 pg/mL. Chest x-ray demonstrated right interstitial infiltration and bilateral pleural effusion. The echocardiogram revealed severe concentric hypertrophy of the left ventricle, an apical sparing left ventricle longitudinal strain, and an ejection fraction of 68%. A cardiac MRI showed concentric biventricular hypertrophy associated with extensive diffuse late gadolinium enhancement, suggestive of cardiac amyloidosis. Screening resulted in a Perugini score of 1 on Tc-PYP scintigraphy, elevated Kappa and Lambda light chains on serum, and kidney biopsy positive for amyloidosis. Hematology-oncology consultation was done and a daratumumab-CyBorD protocol was started.

Conclusions:
This case elucidated a stepwise diagnostic approach of cardiac amyloidosis in a patient presenting with signs and symptoms of heart failure. Amyloid AL cardiac amyloidosis and its repercussions are severe because it not only compromises by being infiltrative but also by its toxic capacity. A high index of suspicion and a multidisciplinary approach is needed in order to improve quality of life and prolong survival.
Abstract 13864: Can Catheter Ablation Be Effective in Patients With Persistent Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction Diagnosed Using HFA-PEFF Score?
Authors: Nakasuka Kosuke , Oishi Yukako , Tsuruta Yoshiro , Ishida Marina , Kawada Yu , Mori Kento , Kikuchi Shohei , Kitada Shuichi , Goto Toshihiko , Seo Yoshihiro
Published: June 2023

Background:
The efficiency of atrial fibrillation (AF) ablation for heart failure with preserved ejection fraction (EF) (HFpEF) has not been well investigated due to the difficulty of diagnosing HFpEF. The HFA-PEFF score from the European Society of Cardiology has been introduced as a new non-invasive diagnostic system for HFpEF.

Methods:
We studied 101 persistent AF patients with EF≥50% who underwent first catheter ablation (age 70±10 years, 68 men). The HFA-PEFF score was calculated as a sum of points in echocardiographic functional and morphological, and biomarker (brain natriuretic peptide: BNP) domains. Based on the HFA-PEFF score, patients were divided into High-group (score of ≥5, n=34) and Low-group (score of <5, n=67).

Results:
The High-group had older, higher BNP levels, left atrial volume index (LAVI), and E/e' than those in the Low-group. However, after 1.1±0.3 procedures, BNP levels (335±247 to 111±95 vs. 167±107 to 90±134pg/mL) and LAVI (62±19 to 44±12 vs. 52±22 to 42±17ml/m
2
) were significantly decreased in each (all p<0.05 by paired t-test) and reached levels that were not significantly different in both groups. In addition, during 13.9±15.6 months after the first procedure, although recurrences of AF/atrial tachycardia were observed in 28 patients, the Kaplan-Meier curve analysis revealed no significant difference in recurrence-free survival between the two groups (Log-rank p=0.944, Figure).

Conclusion:
These data suggest that AF catheter ablation is effective even in patients diagnosed with HFpEF by a high HFA-PEFF score in terms of maintaining sinus rhythm comparable to patients with lower scores and improvements in cardiac function.
Abstract 13889: Effect of Eicosapentaenoic and Docosahexaenoic Acid Supplementation on Noncalcified Coronary Plaque and Coronary Artery Calcium Score in Subjects With Coronary Artery Disease According to Hypertension Status
Authors: Hariri Essa H , Asbeutah AbdulAziz A , Malik Abdulaziz , Chedid Georges , Welty Francine K
Published: June 2023

Introduction:
Higher amounts of noncalcified plaque and higher coronary artery calcium (CAC) scores are associated with increased cardiovascular events and mortality. The effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on noncalcified coronary plaque and more advanced calcified plaque as measured by the CAC score according to hypertensive (HTN) status is unknown.

Methods:
A total of 242 subjects with coronary artery disease (CAD) on statin were randomized to 3.36 g of EPA+DHA or none (control) for 30 months. Coronary plaque composition and CAC scores were measured with computed tomographic coronary angiography at baseline and 30-month follow-up.

Results:
Mean (SD) age was 63.1 years (7.7); mean (SD) LDL-C: 77.8 mg/dL (27.3) and median [IQR] triglyceride (TG): 117.5 mg/dL [81.3,166.8]. Despite a significantly higher CAC score at baseline in HTN subjects, both HTN and normotensive (NTN) subjects had similar CAC progression over 30 months with no difference between EPA+DHA and control groups (Figure B). NTN subjects on EPA+DHA had a 20.7% reduction in TG level and 36.6% lower neutrophil count, a marker of inflammation, and lack of progression of noncalcified plaque compared to control who had progression (median % change: -7.6 vs 13.2 mm
3
/mm, P=0.008) (Figure A). In contrast, HTN subjects on EPA+DHA and control had progression of noncalcified coronary plaque with no significant difference between the two groups (Figure A)

Conclusions:
EPA+DHA prevented progression of noncalcified plaque in NTN subjects but not HTN subjects with no effect on more advanced plaque which has calcified in the setting of low LDL-C and TG levels. The benefit of EPA+DHA in CAD patients on statin therapy appears limited to noncalcified coronary plaque in NTN subjects. Whether this benefit is related to more favorable effects on inflammation based on blood pressure status should be examined further.
Abstract 13918: Combined ECG Precordial Voltage and Troponin-T in Stress Cardiomyopathy versus Anterior STEMI
Authors: Majmudar Ushma V , Zou Fengwei , Pang Li , Pancholi Parth , Schenone Aldo L , NEVELEV DMITRIY , Garcia Mario J
Published: June 2023

Introduction:
Stress cardiomyopathy (SC) and anterior ST elevation myocardial infarction (AMI) share similar clinical and echocardiographic features on initial presentation, complicating their differentiation. Previously, subtle differences in 12-lead ECG between the two have been reported.

Hypothesis:
We propose that higher precordial R-wave amplitude on ECG and lower biomarkers values can serve as reliable predictors of SC during initial triage.

Methods:
Among patients admitted to a single center from 2015-2019 undergoing left heart catheterization (LHC) for suspected AMI, 76 patients with either LHC-proven SC or AMI (38 each) were included. All patients had transthoracic echocardiography (TTE) performed within 24 hours of LHC. Patients were excluded when TTE quality was poor. Left ventricular ejection fraction (LVEF) and speckle-tracking global longitudinal strain (GLS) were calculated from transthoracic apical views. Non-parametric variables were analyzed using Wilcoxon rank sum test. Sensitivity and specificity analyses were performed using ROC curves.

Results:
LVEF (33
+
9% vs 33
+
8%) and GLS (-7.5
+
2.8% vs -7.9
+
3.3%) were similar in both groups. R-wave amplitude in ECG leads V1-V2 was higher in SC compared to AMI (V1: 0.96 vs 0.54 mV, p = 0.035; V2: 1.46 vs 0.75 mV, p = 0.037). At index admission, peak pro-BNP was higher (22198 vs 3098, p = 0.002) and peak Troponin-T (1.43 vs 236, p <0.001) was lower in SC. Integrating peak Troponin-T and V1+V2 R-wave amplitudes differentiated SC from AMI with sensitivity = 92% and specificity = 73%.

Conclusions:
Despite having similar extent of LV systolic dysfunction when compared to AMI patients, SC patients have lower troponin elevation and R-wave amplitude reduction at presentation. These characteristics may be useful for selecting patients who do not require urgent invasive diagnostic evaluation.
Abstract 13936: Increased Bone Morphogenetic Protein 10 in Pulmonary Hypertension
Authors: Llucia-Valldeperas Aida , Van Wezenbeek Jessie , Groeneveldt Joanne , Smal rowan , Sanchez-Duffhues Gonzalo , Becher Clarissa , Vonk Noordegraaf Anton , Bogaard Harm J , Goumans Marie Jose , De Man Frances S
Published: June 2023

Introduction:
Pulmonary Hypertension (PH) is characterized by increased right atrial (RA) stretch and pressure. The major genetic predisposing risk factor for PH involves mutations in the bone morphogenetic protein (BMP) receptor 2 (BMPR2), for which BMP9 and BMP10 are ligands. Although BMP9 is mostly produced by hepatocytes, BMP10 is predominantly produced by adult RA cardiomyocytes. Therefore, its role is of interest in PH despite an elusive BMP10 release mechanism.

Hypothesis:
Increased RA wall stress in PH may be a trigger for BMP10 secretion.

Methods:
We first investigated BMP10 gene and protein expressions, as well as BMP activity, in RA tissue samples from control (N=5) and PH-patients (N=4). We also quantified BMP10, BMP9, IL-6 and active TGF-β plasma levels in controls (N=16) and PH-patients (N=48) by ELISA. We studied BMP10 and BMP9 activities, using a BMP-inducible reporter assay. Last, we established correlations between BMP10 activity and PH clinical parameters.

Results:
BMP10 mRNA, protein and activity (pSMAD1/5/8 and ID3) were increased in RA tissue of PH-patients compared to controls (Figure1 A-E). BMP10, BMP9 and IL-6 plasma levels were also augmented (Figure1 F-H); while TGF-β plasma levels, and BMP10 and BMP9 activities between PH-patients and controls were preserved. Finally, we divided the PH cohort on median BMP10-activity (0.33 AU). Higher BMP10 activity in PH-patients was associated with diminished RA compliance, reduced right ventricular function, lower stroke volume and elevated NT-proBNP (Figure1 I).

Conclusions:
Although BMP10 plasma levels were increased, BMP10 activity was preserved in PH-patients, probably because of high inflammatory cytokines, such as IL-6. High BMP10 activity was associated with increased RA pressure and worse disease severity in PH-patients.
Abstract 13941: FTO Demethylase Mediates Altered N
6
-methyladenosine (m
6
A)-RNA Modification in Tyrosine Kinase Inhibitor-Induced Cardiotoxicity
Authors: Ma Yan , Han Dong , Wang Tian Hu , Sun Shasha , Zhang Yang , Cao Feng
Published: June 2023

Background:
N
6
-methyladenosine (m
6
A) methylation is dynamically regulated by writers and erasers, and ultimately affects RNA splicing, translation, and stability after by recognized readers, thereby affecting disease progression. Sunitinib (SUN) is a tyrosine kinase inhibitor (TKI) widely used to treat different types of solid and hematological tumors, but its cardiotoxicity limits its clinical application. FTO is an m
6
A demethylase has been shown to play an important role in various heart diseases. In this study, we deciphered the methylation modification of m
6
A mRNA in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) post sunitinib treatment and assessed whether FTO regulated pyroptosis-related m
6
A methylated transcripts in SUN-treated hiPSC-CMs.

Methods and Results:
The global m
6
A RNA-methylation level was increased in SUN-treated hiPSC-CMs and was parallel with a positively correlated cellular damage level (LDH leakage). Through a genome-wide analysis of m
6
A mRNA methylation by MeRIP-Seq and RNA-seq, we identified a total of 2614 peaks with significant changes. qRT-PCR, immunofluorescence, and Western blot revealed that FTO was the most evidently changed m
6
A modifying enzymes in SUN-treated hiPSC-CMs (downregulated fold change being 0.43). Interestingly, the loss of FTO in hiPSC-CMs exposed to SUN was positively associated with cellular damage level and pyroptosis-

associated NLRP3 and ASC transcripts levels. To further test if TKI-induced increase in m
6
A-RNA modification is mediated through FTO loss, hiPSC-CMs, overexpressed with ectopic FTO, showed significant restoration of m
6
A methylation level and normalization of pyroptosis-associated transcripts (NLRP3 and ASC) after exposure to SUN. To evaluate the effect of FTO on the methylation of RNA transcripts of NLRP3 and ASC, MeRIP assay demonstrated that FTO tightly controlled the methylation levels of NLRP3 and ASC transcripts, and demethylation of these transcripts by FTO accelerated their degradation rate.

Conclusion:
This study revealed that TKI-induced loss of FTO may mediate the decreased m
6
A-RNA methylation and TKI-induced cardiotoxicity pathogenesis by dysregulating the methylation and expression of pyroptotic transcripts NLRP3 and ASC.
Abstract 13963: Short-Coupled Variant of Torsade de Pointes: A Rare Entity With Unknown Etiology and Malignant Phenotype
Authors: krishnan suraj , Torrado Juan F , Duarte Gustavo , Marashly Qussay , krumerman andrew
Published: June 2023

Introduction:
Torsade de Pointe (TdP) is defined as a polymorphic VT (pVT) typically associated with QTc prolongation. However, not all pVT occur in the presence of QTc prolongation and respond to different forms of therapy. Hence defining their etiology is important.

Case:
A 48-yo Female with H/O resolved peripartum cardiomyopathy, hypertension & obesity presented to the hospital following a syncopal episode. Her BP was 207/125 mmHg, and ECG showed sinus rhythm with a QTc of 436. No history of heart disease or SCD in her family. Physical exam was unremarkable, labs showing K-3.2 without troponin elevation. On day 2, she developed a pVT requiring defibrillation and amiodarone. Telemetry revealed a PVC causing R on T phenomenon with a coupling interval of 260 msec prior to initiation of SVT with QTc 484 and K-2.8. On day 3, despite electrolyte correction, she had multiple non-sustained pVTs with QTc 482. Amiodarone was switched to lidocaine and QTc normalized to 447. TTE and LHC were unremarkable with a small LV aneurysm on cMRI. On day 4, the patient continued to have incessant runs of pulseless pVT requiring defibrillation and started on verapamil. A 12 lead ECG during VT demonstrated left bundle branch mimicry with a left axis consistent with a VT exit site along the RV moderator band. The patient underwent emergent ablation with targets along the right anterolateral papillary muscle. AICD was placed prior to discharge.

Discussion:
The critical timing of PVC falling on the peak of the preceding T wave differentiates ‘Short-coupled TdP’ from other malignant VTs with normal QTc. These PVCs typically originate from distal ramifications of Purkinje fibers in both ventricles. PVC morphology with LBBB pattern, left axis and late precordial R-S transition points to the moderator band as the source of idiopathic VT. Contrasting with typical TdP, medical management with Quinidine and Verapamil may be efficacious. Catheter ablation is curative in most cases.
Abstract 13994: Time to Treatment and Efficacy of IL-1 Blockade With Anakinra in ST-Segment Elevation Myocardial Infarction
Authors: Del Buono Marco Giuseppe , Damonte Juan Ignacio , chiabrando juan guido , MARKLEY ROSHANAK , Turlington Jeremy , TRANKLE Cory R , Moroni Francesco , Kang Le , Roberts Charlotte , Bhardwaj Hem , Kontos Michael C , Biondi-Zoccai Giuseppe G , Van Tassell Benjamin W , Abbate Antonio
Published: June 2023

Introduction:
Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has recently showed to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI.

Hypothesis:
The aim of this study was to determine whether time to anakinra treatment influences the efficacy on systemic inflammation and HF events in patients with STEMI.

Methods:
This is a secondary analysis of the data from the three VCUART clinical trials, including adult patients with STEMI presenting within 12 hours of pain onset, enrolled within 12 hours of reperfusion and randomly assigned to anakinra or placebo for 14 days. We divided the cohort in two groups based on the median time from percutaneous coronary intervention (PCI) to investigational drug, and analyzed the effects of anakinra on the area-under-the-curve for C reactive protein (AUC-CRP) and on incidence of the composite endpoint of death or new onset HF.

Results:
We analyzed data from 139 patients: 84 (60%) treated with anakinra and 55 (40%) with placebo. The median time from PCI to investigational treatment was 271 [182-391] minutes. The AUC-CRP was significantly higher in patients receiving placebo versus anakinra both in those with from PCI to treatment <271 min (222.6 [103.9-325.2] vs 78.4 [44.3-131.2], p<0.001) and those with time from PCI to drug ≥271 min (235.2 [131.4-603.4] vs 75.5 [38.9-171.9, p<0.001]. Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment <271 min (5 [11%] vs 9 [36%], log-rank p value=0.014) as well as in patients with time from PCI to drug ≥271 min (2 [5%] vs 7 [23%], log-rank p value= 0.046).

Conclusions:
In patients with STEMI treated with anakinra within 12 hours of reperfusion, the therapeutic window of IL-1 blockade on the systemic inflammatory response and on HF events in reperfused STEMI appears to be stable for several hours.
Abstract 140: Sex-specific Behavioral And Neurological Outcomes After Experimental Asphyxial Cardiac Arrest
Authors: Russell Ashley L , Dimeo Emma , Kline Kelsey E , Gober Ian , Stezoski Jason P , Drabek Tomas , Kochanek Patrick M , Wagner Amy K
Published: June 2023

Background:
Although survival rates after asphyxial cardiac arrest (ACA) have improved, survivors face neurological disability from hypoxic ischemic brain injury. Hippocampal CA1 and striatum, which affect cognitive function, are vulnerable. Targeted temperature management (TTM) is the only recommended intervention to improve outcome, yet preclinical studies are lacking on sex-linked behavioral and neurological outcomes after TTM.

Hypothesis:
TTM produces sex-specific differences in CA1 and striatal associated behavioral and neurological outcomes after ACA.

Methods:
Adult male and female Sprague-Dawley rats underwent sham or 5-min no-flow ACA. Temperature was controlled for 18h post-ACA at either 37-38°C (normothermia; n=9 males; 14 females) or 36-37°C (TTM; n=9 males; 8 females). Rats underwent neurological deficit scoring (NDS) and behavior testing over 14d. Behavior measures included: coordination, balance, sensorimotor function [acoustic startle response (ASR)] and myoclonus. Neuropathology was examined (cell death [CA1] and microglial infiltration [CA1 and striatum]) at 14d.

Results:
After ACA, females were less likely to achieve ROSC vs males (76% vs 92%). Females had a longer time to ROSC (p<0.05); but insult severity was similar between sexes based on post-ROSC blood gases. Females had lower NDS vs males at 1-3d post-ACA (p<0.05). ACA females had better coordination, balance, lower ASR, and fewer myoclonic events vs males (p<0.05). ACA females and males had similar amounts of CA1 dead (eosinophilic) and degenerated (fluorojade-B+) neurons and microglia (Iba1). ACA did not impact the number of striatal microglia in either sex vs sham; however more striatal microglia were “activated” than “resting” after ACA. TTM improved survival and NDS in males and females (p<0.05). TTM improved coordination and balance only in males (p<0.05). TTM did not reduce increases in ASR or CA1 death/degeneration. Ongoing work is exploring the effect of TTM on microglial number/activation.

Conclusions:
Females post-ACA have a lower ROSC but better behavioral outcomes vs males. TTM selectively improved behavioral recovery in males but did not impact CA1 injury. We provide preclinical insight into sex-specific ACA responses, using TTM as a therapy.