bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12822: Prediction of New-Onset Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy Using RNA-Sequencing of Plasma Small Non-Coding RNAs
Authors: Yasuda Risako , Akita Keitaro , Hasegawa Kohei , Maurer mathew S , Tower-Rader Albree , Fifer Michael A , Topkara Veli , Reilly Muredach P , Shimada Yuichi
Published: December 2023

Background:
It is known that about 20% of patients with hypertrophic cardiomyopathy (HCM) develop atrial fibrillation (AF), which can lead to stroke and worsening of heart failure. The current clinical model to predict new-onset AF in patients with HCM (HCM-AF score) offers only modest accuracy. RNA-sequencing (RNA-Seq) can determine concentrations of thousands of small non-coding RNAs (sncRNAs) in plasma.

Hypothesis/Aims:
To test the hypothesis that RNA-Seq of plasma sncRNAs predicts new-onset AF in HCM.

Methods:
In this prospective, multi-center cohort study, we conducted RNA-Seq of 3,740 plasma sncRNAs at enrollment on 283 patients with HCM without a prior history of AF. The outcome was new-onset AF. We developed a sncRNA-Seq-based LASSO classification model (sncRNA-Seq-based model) to predict new-onset AF using data from one institution (training set, n=193). We tested the predictive ability of the model in independent samples from the other institutions (test set, n=90). We also developed a clinical model with LASSO using all components of HCM-AF score - i.e., left atrial diameter, age, age at HCM diagnosis, and New York Heart Association functional class ≥2. We then compared the area under the receiver-operating characteristic curve (AUC) between the sncRNA-Seq-based model and the clinical model in the test set.

Results:
During a median follow-up of 2.8 [1.9-5.1] years, 25 patients (13%) in the training set and 7 (8%) in the test set developed new-onset AF. Using the sncRNA-Seq-based model developed in the training set, the AUC to predict new-onset AF in the test set was 0.82 (95% confidence interval [CI] 0.71-0.94,
Figure
). This model outperformed the clinical model (AUC 0.59; 95% CI 0.38-0.81; Delong’s test P=0.02).

Conclusion:
This study serves as the first to demonstrate the ability of plasma sncRNA-Seq to predict new-onset AF in patients with HCM. The prediction model may help physicians identify patients with HCM who are at high risk of developing new-onset AF.
Abstract 12908: Non-Fatal Trial Endpoints of Drug Interventions in Heart Failure
Authors: Raso Vagner
Published: December 2023

Introduction:
The Food and Drug Administration (FDA) provides guidance on the use of endpoints for drug approvals in heart failure (HF).

Hypothesis:
The aim of this study was to systematically review whether clinical studies in HF report the FDA recommendations for endpoints.

Methods:
All studies targeting HF available on the clinical trials platform from the National Library of Medicine were analyzed. The FDA recommends a decrease in mortality as the primary efficacy endpoint and an increase in survival as the safety endpoint. Others include single or composite scores of hospitalizations, biomarkers, or symptoms and/or physical function.

Results:
Trials (n=4,978) were narrowed down to 1,299 (26%) studies with an active, but not recruiting, enrolling by invitations, not yet recruiting, and recruiting statuses. Only 132 (3%) studies using intervention with drugs reported endpoints. Up to 7,200 participants were randomly (n=95, 72%) assigned to parallel designs (n=81, 61%) followed by single group (n=19, 14%) or crossover designs (n=18, 14%) with open label (n=48, 36%) or quadruple masking methods (n=29, 22%). Interventions tested sodium-glucose co-transporter 2 (n=21, 16%) and angiotensin receptor-neprilysin inhibitors (n=13, 10%). Dapagliflozin (n=8, 8%), Sacubitril and Valsartan (n=6, 6%) followed by Levosimendan, Metformin, or Warfarin (n=3, 3%) were compared to placebo (n=51, 53%). Equivalence trials (n=35, 27%) analyzed Sacubitril and Valsartan (n=5, 14%), Dapagliflozin, Beta-hydroxybutyrate Ester, or Sacubitril and Valsartan with Para-aminohippurate, Lohexol, and Aprepitant (n=2, 6%). Most studies (n=55, 42%) assessed endpoints related to symptoms and/or physical function. Other endpoints included cardiac function (n=24, 18%) and biomarkers (n=19, 14%) followed by mortality and survival (n=18, 14%) or hospitalization (n=5, 4%).

Conclusions:
Most studies assessed symptoms, physical function, cardiac function, or biomarkers for primary endpoints. They have included non-fatal endpoints such as patient-reported outcomes or objective indicators likely due to the increasing number of patients with worsening heart failure in outpatient settings.
Abstract 12928: Deep Learning-Derived Characterization of Lung Tissue Predicts Future Diagnosis of Heart Failure
Authors: Hou Cody R , Ramo Joel , Kany Shinwan , Friedman Samuel , Ellinor Patrick T , Pirruccello James
Published: December 2023

Background:
Cardiovascular and respiratory diseases are intrinsically coupled. Scalable methods for quantifying cardiac and pulmonary structures may improve our understanding of cardiopulmonary disease.

Aims:
We sought to quantify textural parameters of the lung fields in cardiovascular magnetic resonance imaging (cMRI) from the UK Biobank. We then sought to determine their genetic basis and their relationship with heart failure.

Methods:
We fine-tuned a convolutional neural network to segment left and right lung on cMRIs performed during expiratory breath hold. A random sample of 300 coronal slices from unique individuals was manually annotated for fine-tuning. The model was applied to 912,320 coronal cMRI images. Segmentation masks were stacked, and lung volume and texture metrics were quantified from the resulting 3D masks using the
pyradiomics
Python package.

Results:
After quality control, we computed lung traits in 45,179 participants. Mean lung volume was 2.19 ± 0.49 L in women and 2.87 ± 0.68 L in men. After adjustment for age and sex, lung volume was associated with forced vital capacity (FVC) (β = +0.30 L per SD, p < 1.1 х 10
-308
). After adjustment for age and sex, body size traits (e.g. standing height and heel bone mineral density) were associated with increased lung volume, whereas adiposity traits (e.g. body mass index and visceral adipose tissue) were associated with decreased lung volume. Greater heterogeneous and coarse lung textures were associated with an increased risk of heart failure (1-SD hazard ratios: 1.21 (95% CI [1.12, 1.31]) and 1.32 (95% CI [1.18, 1.47]), respectively). This association was still significant among non-smokers and after adjustment for left ventricular ejection fraction.

Conclusions:
Deep-learning derived measures of lung texture are linked to future heart failure. Our findings suggest that heart failure may manifest as changes in lung tissue that are detectable on MRI before changes in cardiac function.
Abstract 12977: Prevalence and Incidence of Diastolic Dysfunction in Patients With Functional Tricuspid Regurgitation
Authors: Naser Jwan A , Pislaru Sorin , Nkomo Vuyisile T , Scott Christopher , Kennedy Austin , Eleid Mackram F , Reddy Yogesh , Lin Grace , Pellikka Patricia A , Borlaug Barry A
Published: December 2023

Introduction:
Isolated functional tricuspid regurgitation (FTR) in the absence of structural heart disease may develop secondary to elevation in left heart pressures caused by left ventricular diastolic dysfunction (DD), as in heart failure with preserved ejection fraction (HFpEF). FTR may also herald the presence of occult DD or indicate greater risk for new-onset DD. However, prevalence and incidence of diastolic dysfunction (DD) in isolated FTR have not been studied.

Aims:
Investigate the prevalence and incidence of DD across the different severities of FTR of unclear cause.

Methods:
Adults with normal EF and without structural heart disease undergoing echocardiography at a tertiary medical center with a repeat study ≥6 months from baseline were identified. Severe DD was defined by ≥3/4 abnormal DD parameters (medial e’, medial E/e’, tricuspid regurgitation velocity, left atrial volume index) and moderate DD by ≥2.

Results:
Among 30,428 patients (median age 60; 50% women), FTR was absent in 73%, mild in 22%, moderate in 4%, and severe in 0.4%. Severe DD was present in 2%, 5%, 11%, and 13% patients, respectively, (p<.001) and moderate DD in 9%, 19%, 31%, and 48%, respectively (p<.001). The association of DD with increasing FTR was independent of all clinical characteristics. Over median 3.0 (IQR 1.5-5.4) years, incident severe and moderate DD developed more frequently with increasing FTR severity (
Figure)
. Findings were confirmed in a propensity-matched subset where patients were matched for age, sex, BMI, atrial fibrillation, and comorbidities and in patients without lung disease or ≥moderate right ventricular enlargement.

Conclusions:
Patients with FTR of undefined etiology commonly have DD suggesting the presence of underlying left heart disease. Patients without apparent DD or HF at baseline who have FTR remain at significantly increased risk of developing DD over follow-up and may be a target population for therapies to prevent progression to clinical HFpEF.
Abstract 12978: Real-World Treatment Patterns in Hispanic and White Patients With Pulmonary Arterial Hypertension (PAH) in the United States
Authors: Melendres-Groves Lana , Tang Wenze , Germack Hayley D , Liu Zhiwen , Sadik Kay
Published: December 2023

Introduction:
ESC/ERS guidelines recommend initial double oral combination therapy (endothelin-receptor antagonist plus phosphodiesterase 5 inhibitor) in low or intermediate risk PAH patients without cardiopulmonary comorbidities. Upfront use of prostacyclin pathway analogue (PPA) is recommended for patients with high risk of 1-year mortality. Few studies have evaluated treatment patterns/adherence in PAH patients across ethnic groups.

Aims:
To describe demographic/clinical characteristics and treatment patterns in US Hispanic and White PAH patients.

Methods:
A retrospective, observational, analysis using Optum’s de-identified Clinformatics
®
Data Mart database identified patients aged ≥18 years with pulmonary hypertension (PH) diagnosis (excluding chronic thromboembolic PH) and were new users of PAH medications. Index date was the 31
st
day after first PAH-specific medication use (1 Jan 2016-30 Jun 2022); the 30-day window between first PAH medication use and index date was used to identify the initial PAH regimen. Patient characteristics and PAH treatment patterns were analyzed descriptively, with standardized mean differences (SMD) between cohorts assessed (SMD >0.1 indicated significant difference).

Results:
Hispanic patients were younger, with lower income, lower education level, and higher comorbidity burden than White patients (Table). Few patients received initial combination PAH treatment with similar use of combination therapy in the two cohorts (~14% in each). Hispanic patients were less likely to receive a PPA-containing index treatment regimen and had lower index treatment adherence (Table).

Conclusions:
In Hispanic and White patients, index combination PAH therapy use was low. Hispanic patients were less likely to receive a PPA-containing index treatment and had lower index treatment adherence. Further research and awareness of the influence of ethnicity on treatment management is needed to improve PAH care.
Abstract 13043: LDL-C, Lp(a) and Hs-CRP Each Predict Future Cardiovascular Events After ACS on High-Intensity Statin Therapy. An Analysis of the ODYSSEY OUTCOMES Trial
Authors: Steg Philippe G , Szarek Michael , Jukema J W , Bhatt Deepak L , Bittner Vera A , Diaz Rafael , fazio Sergio , Garon Genevieve , Goodman Shaun G , Harrington Robert A , White Harvey D , Zeiher Andreas M ,   ODYSSEY OUTCOMES Investigators
Published: December 2023

Background:
Atherosclerotic cardiovascular disease (ASCVD) risk has been jointly associated with levels of LDL cholesterol (LDL-C), lipoprotein [Lp](a)] and the inflammatory marker high-sensitivity C reactive protein (hsCRP). It is unclear whether and to what extent each of these biomarkers predict ASCVD risk after acute coronary syndrome (ACS), particularly in the era of intensive LDL-C lowering. Recent analysis of 3 trials in stable ASCVD patients with hypertriglyceridemia suggested that hsCRP may be a stronger predictor for recurrent events than LDL-C; however, only 52% received high-intensity statin.

Methods:
The ODYSSEY OUTCOMES trial enrolled post-ACS patients not at goal for atherogenic lipoproteins a median of 2.6 months after ACS and on treatment with maximum tolerated (89% high-intensity) atorvastatin or rosuvastatin. Absolute risk of major adverse cardiovascular events (MACE, the primary composite outcome of coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke or unstable angina hospitalization) and all-cause death were analyzed as a function of baseline LDL-C, hs-CRP, and Lp(a) values in patients randomized to the placebo arm via natural cubic splines from Poisson regression models, adjusted for age, sex, diabetes, BMI, current smoking, and the other 2 predictor variables.

Results:
Among 9149 evaluable patients, median (Q1-Q3) LDL-C, hsCRP, and Lp(a) were 81 (71-97) mg/dL, 1.7 (0.8-3.9) mg/L, and 21.4 (6.6-60.1) mg/dL, respectively. For each parameter, a higher baseline value was associated with a substantial increase in risk of MACE (
Figure
, all spline p<0.0001). LDL-C and hsCRP were associated with all-cause death (p<0.0001), but not Lp(a) (p>0.05).

Conclusion:
In ACS patients receiving intensive statin therapy and not at goal for atherogenic lipoproteins, LDL-C, hs-CRP, and Lp(a) were independent predictors of MACE. LDL-C and hsCRP were independent predictors of all-cause death.
Abstract 13189: Early Evolution of SCAI-Shock Stage and In-Hospital Mortality in a CICU Population From the Critical Care Cardiology Trials Network-CCCTN
Authors: Skove Stephanie , Berg David , Guo Jianping , Katz Jason N , Van Diepen Sean , Morrow David , Shah Kevin S ,   CCCTN Investigators
Published: December 2023

Introduction:
The SCAI shock staging system is a useful tool for categorizing cardiogenic shock (CS) severity. Presenting SCAI shock stage is known to be associated with in-hospital mortality. However, few studies have evaluated the prognostic significance of very early evolution in SCAI stage.

Methods:
The Critical Care Cardiology Trials Network (CCCTN) is a multicenter network of tertiary CICUs in the US and Canada coordinated by the TIMI Study Group (Boston, MA). Among consecutive CICU admissions with CS, we captured clinician assigned SCAI shock stage at 0-6 hours and 6-12 hours post-CICU admission. Cases were classified as having an improved (e.g., D to C), stable, or worsened SCAI stage between these time periods. The association between change in SCAI stage and in-hospital mortality was evaluated using logistic regression, adjusting for age and 0-6 hour SCAI stage.

Results:
Among 793 CS admissions between 10/2021 to 09/2022, 73% had a stable SCAI stage, 13% had an early worsening SCAI stage, and 14% had an improving SCAI stage during the initial 12 hours of CICU admission. Compared to cases with stable SCAI stage, cases with worsened SCAI stage had greater use of renal replacement therapy and mechanical circulatory support (Fig 1A) and a longer hospital stay (median 27.5 [IQR 13.6-36.7] vs. 14.7 [8.6-24.9] days, p=0.006). In-hospital mortality among cases with a worsened SCAI stage was 61%, compared to 31% with stable and 26% with improved SCAI stage (Fig 1B). Classification by both initial and 12h SCAI stage revealed a gradient of mortality risk (Fig 1C). Compared to cases with stable SCAI stage, those with worsened SCAI stage had higher adjusted risk of in-hospital mortality (OR: 5.1[95% CI 3.1-8.3]).

Conclusion:
Patients with early worsening of SCAI stage have a markedly higher risk of in-hospital mortality than those with a stable SCAI stage. The prognostic implication of early evolution in SCAI stage in patients with CS adds to that of SCAI stage on CICU presentation.
Abstract 13242: Annual Body Weight Change and Subsequent Prognosis in Heart Failure With Preserved Ejection Fraction: Insights From the PURSUIT-HFpEF Registry
Authors: Okada Masato , Tanaka Nobuaki , Iwakura Katsuomi , Seo Masahiro , Hayashi Takaharu , Yano Masamichi , Nakagawa Akito , Nakagawa Yusuke , Tamaki Shunsuke , Yamada Takahisa , Yoshio Yasumura , Sotomi Yohei , Nakatani Daisaku , Hikoso Shungo , Sakata Yasushi ,   the OCVC Heart Failure Investigators
Published: December 2023

Introduction:
Maintaining optimal body weight is important in heart failure management. Weight gain (WG) may signal excessive caloric intake and fluid retention, whereas weight loss (WL) would imply cachexia. Both conditions could affect the prognosis of heart failure with reduced ejection fraction. However, the significance of WG and WL in patients with heart failure and preserved ejection fraction (HFpEF) has not been well established.

Methods:
An analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. Of 1231 patients who enrolled in the registry, we enrolled 662 patients (age, 82±9 years; females, 54.1%; body mass index, 22.3±4.3kg/m
2
; atrial fibrillation, 38.3%) whose weight at discharge and one year later were both available. WG and WL were defined as a gain or loss of ≥5% weight between baseline and 1 year, respectively. Other patients who did not demonstrate a significant change in weight were categorized as having a stable weight (SW). All-cause mortality was the primary endpoint.

Results:
During 1-year, the median body weight slightly increased from 52.1 (interquartile range [IQR]: 45.1-61.9) to 53.0 kg (IQR 45.0-63.0) kg (p <0.001), with a median change of 0.6 kg (IQR: -1.8-2.8). A total of 182 (27%), 125 (19%), and 355 (54%) patients experienced WG, WL, and SW, respectively. During a follow-up of 603 days (IQR: 329-982), 149 patients died. The mortality rate was highest in patients experiencing WL, followed by those experiencing WG and SW (30.2% vs. 21.5% vs. 18.0%, respectively; log-rank p = 0.006). After adjusting for potential confounders, Cox regression analysis revealed that WL, not WG, was independently associated with higher mortality (hazard ratio 2.44 [95% CI 1.51-3.95], p <0.001).

Conclusions:
Significant number of patients with HFpEF experienced WG and WL within a year. Patients who experienced WL had a higher risk of mortality compared to those who experienced WG and SW. These results highlight the importance of monitoring body weight changes in the management of HFpEF.
Abstract 13280: Plasma Extracellular microRNAs Associated With Cardiovascular Disease Risk Factors in Middle-Aged and Older Populations
Authors: Karlin Hannah , Sooda Meera , Larson Martin , Rong Jian , Huan Tianxiao , Mens Michelle M , Rooij Frank v , Ikram M. A , Courchesne Paul , Freedman Jane E , Joehanes Roby , Mueller Gregory P , Kavousi Maryam , Ghanbari Mohsen , Levy Daniel
Published: December 2023

Background:
Extracellular microRNAs (miRNAs) are a class of non-coding RNAs that resist degradation and remain stable in the extracellular milieu where they contribute to various physiological and pathological processes by facilitating intercellular signaling. Previous studies have reported associations between miRNAs and cardiovascular diseases (CVD); however, the plasma miRNA signatures of CVD and its risk factors have not been fully elucidated at the population level.

Methods:
Plasma miRNA levels were measured in 4,440 Framingham Heart Study (FHS) participants from the Third Generation and Omni II cohorts using qRT-PCR. Linear regression analyses were conducted to test the cross-sectional associations of each miRNA with CVD risk factors, including systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides, HDL and total cholesterol, blood glucose, BMI, and cigarette smoking. Prospective analyses of the associations of miRNAs with new-onset obesity, hypertension, type 2 diabetes, CVD, and all-cause mortality were conducted using proportional hazards regression. A false discovery rate threshold of 0.05 was applied for each risk factor and outcome individually. Replication was carried out in 2,000 Rotterdam Study (RS) participants with data on plasma miRNA levels measured using RNA-seq. Pathway enrichment analyses were conducted and gene targets were predicted for miRNAs associated with five or more risk factors in FHS.

Results and Conclusions:
In FHS, six miRNAs (miR-193b-3p, miR-122-5p, miR-365a-3p, miR-194-5p, miR-192-5p, miR-193a-5p) were associated with five or more CVD risk factors. This miRNA signature was enriched for biological processes and cellular pathways associated with CVD; many of the genes annotated to these pathways are predicted targets of the identified miRNAs. In RS, miR-193b-3p, miR-194-5p, and miR-193a-5p were associated with two or more risk factors. Prospective analysis revealed eight miRNAs associated with all-cause mortality only in FHS, including miR-193b-3p, miR-122-5p, miR-192-5p, and miR-193a-5p. These findings suggest plasma miRNA levels are associated with CVD risk factors and could provide opportunities to investigate their possible contributions to CVD pathogenesis.
Abstract 13343: Left Ventricular Noncompaction Cardiomyopathy in a Family With Dolichol Kinase Congenital Disorder of Glycosylation
Authors: Xia Eric T , Minga Iva , Lazarus Catherine , Nazari Jose
Published: December 2023

Introduction:
During embryogenesis, failure of spongy, sinusoidal myocardium to condense results in left ventricular noncompaction cardiomyopathy (LVNC). The resulting LV is hypertrophic but loosely organized. LVNC is associated with heart failure (HF), arrhythmias, and thromboembolic events.

Case:
A 41 year old man with a history of non-ischemic HF with recovered ejection fraction associated with signs of LVNC, LV thrombus, and ischemic stroke while compliant with rivaroxaban has been known to cardiology services for years. His brother who also exhibited LVNC and suffered thrombotic events died at age 31 from advanced HF. Uniquely, EKG for both brothers showed exceptionally low ventricular voltage, with P waves of higher amplitude than R waves. Genetic testing revealed a homozygous variant of unknown significance (VUS) in dolichol kinase (c.863_865del)(p.Leu288del) establishing a diagnosis of congenital disorder of glycosylation (DOLK-CDG). Metabolic testing was abnormal and, given phenotypic overlap of the brothers, it is likely that the VUS caused this clinical presentation.

Discussion:
LVNC has never previously been linked with DOLK-CDG. In the literature, 27 patients with DOLK-CDG have been described ranging from 3 days to 16.5 years old at time of death. Nearly all patients expressed dilated cardiomyopathy, while others expressed a combination of ichthyosis, dysmorphism, and neurological dysfunction. Our patient reported good health until presentation with chest pain at age 35 when he was discovered to have ejection fraction of 40% and LV thrombus. The most curious finding was the paradoxically low ventricular EKG voltage in both brothers, dissimilar to the hypertrophic pattern commonly seen in LVNC. Yet all common MR criteria were met, strongly suggesting LVNC. Given the similarities in the presentation between brothers, this patient was preemptively referred for transplant.
Abstract 13727: Cost-Effectiveness of Sotagliflozin in Heart Failure Patients With Preserved and Reduced Ejection Fractions—Results From the SOLOIST-WHF
Authors: Weintraub William S , Dolman Sarahfaye , Kolm Paul , Zhang Zugui
Published: December 2023

Background:
SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) showed patients with diabetes and recent worsening heart failure (HF), sotagliflozin initiated before or shortly after discharge lowered incident cardiovascular deaths, hospitalizations, and HF urgent visits. In this study, we evaluated the cost-effectiveness of sotagliflozin in all patients and those with preserved (HFpEF ≥50%) and reduced (HFrEF <50%) ejection fraction.

Methods:
We ran a Markov microsimulation model based on treatment effects from SOLOIST-WHF, healthcare costs and utilities from national sources, and estimated net costs for sotagliflozin of $434 (range from $407 to $612) monthly, to calculate projected lifetime healthcare costs, HF and CVD events, survival, and quality-adjusted life-years (QALYs) for sotagliflozin vs placebo in SOLOIST-WHF eligible patients from a payer perspective. Outcome measured as the incremental cost-effectiveness ratio (ICER), incremental costs / QALYs gained. Sensitivity analyses assessed and quantified uncertainties.

Results:
Over a lifetime, sotagliflozin compared to placebo added 0.39 QALYs (4.43 vs. 4.04 QALYs) and 0.64 life-years (7.12 vs. 6.48) at an incremental cost of $29,449 (95% uncertainty interval (UI): $26,610-$32,528) for an ICER of $75,510 per QALY gained (UI: $55,640-$98,300). In HFpEF patients, sotagliflozin compared to placebo added 0.43 QALYs (4.53 vs. 4.10 QALYs) and 0.68 life-years (7.14 vs. 6.46) at an incremental cost of $26,615 (UI: $23,376-$29,694) for an ICER of $61,488 per QALY gained (UI: $41,618-$84,280). In HRrEF patients, sotagliflozin added 0.37 QALYs (4.33 vs. 3.96 QALYs) and 0.63 life-years (7.09 vs. 6.46) at an incremental cost of $30,012 (UI: $26,773-$33,251) for an ICER of $77,996 per QALY gained (UI: $58,126-$100,780). The benefit of sotagliflozin in QALY mainly results from the decrease in CVD deaths. Findings were sensitive to drug cost and number of readmissions.

Conclusions:
This study demonstrates that sotagliflozin priced from $407 to $612 per month is a clinically and economically favorable medication in patients with diabetes, recent worsening heart failure, with both preserved and reduced ejection fraction.
Abstract 13732: A Mobile Intervention to Support Self-Care of Patients With Coronary Artery Disease: Preliminary Analysis of a Randomized Controlled Trial
Authors: Li Polly Wai Chi , yu Doris S
Published: December 2023

Background:
Although cardiac rehabilitation is beneficial to all patients with coronary artery disease (CAD), due to the cost implications, such services are confined to those with an acute coronary event or heart failure exacerbation, which limits their accessibility and scalability.

Hypothesis:
Patients with CAD who receive the internet-based CArdiac Rehabilitation Enhancement (i-CARE) intervention would report better changes in self-care, functional status, health-related quality of life (HRQoL) and physiological biomarkers than those who receive usual care.

Aims:
This randomized controlled trial aimed to examine the effects of the i-CARE intervention on self-care behaviors, functional status, HRQoL, blood pressure, waist-to-height ratio and cholesterol level in patients with CAD.

Methods:
CAD patients were recruited in the cardiac clinic of two hospitals in Hong Kong. The intervention consisted of a single face-to-face orientation session and a mobile app consisting of three key user interfaces, including a self-monitoring dashboard with personalized interface according to their own risk profile, an interactive e-library covering various CAD-related self-care dimensions and a chat room for the nurse to provide continuous coaching. The control group received usual care.

Results:
A total of 132 patients with CAD were randomly allocated to the intervention (n = 68) or control group (n = 64). Compared to the control group, the intervention group showed greater improvements in self-care behaviors (β = 5.532, 95% CI: 1.735 - 14.241, p = 0.012), functional status (β = 2.235, 95% CI: 1.092 - 8.286, p = 0.033), HRQoL (β = 6.135, 95% CI: 1.830 - 12.843, p = 0.012), and blood pressure control (β = 12.584, 95% CI: 10.050 - 29.221, p = 0.041) at 12 weeks follow-up. No significant changes in cholesterol level and waist-to-height ratio were found.

Conclusions:
The i-Care intervention improves self-care behaviors, HRQoL, functional status and blood pressure control in patients with CAD. It is warranted to examine the longer-term effects of the i-CARE intervention.
Abstract 13800: Comparison of Predictive Value of Risk Scores for Mortality in Asian Patients With Heart Failure With Preserved Ejection Fraction
Authors: Iwakura Katsuomi , Okada Masato , Tanaka Nobuaki , Koyama Yasushi , OKAMURA ATSUNORI , Heitaro Watanabe , Seo Masahiro , Hayashi Takaharu , Yano Masamichi , Nakagawa Akito , Tamaki Shunsuke , Yamada Takahisa , Yoshio Yasumura , Sotomi Yohei , Hikoso Shungo , Nakatani Daisaku D , Sakata Yasushi ,   The OCVC-Heart Failure Investigators
Published: December 2023

Background:
Several risk scores have been developed to predict mortality and morbidity in heart failure (HF), including heart failure with preserved ejection fraction (HFpEF). However, these scores have primarily been derived from data obtained from Western patients.

Research Questions:
It remains unclear whether these risk factors are applicable to Asian patients, whose pathophysiology of HFpEF may exhibit ethnic differences compared to Western populations.

Aims:
To compare the predictive value of widely used risk scores for mortality in Japanese patients with HFpEF.

Methods:
We assessed the predictive value of three commonly utilized risk scores: MAGGIC, BCN-BioHF, and 3C-HF risk scores, which are applicable to patients with HFpEF. A total of 1,095 patients registered in the PURSUIT-HFpEF, a multicenter registry comprising individuals hospitalized with decompensated HFpEF, were enrolled (mean age 81±9 years, 54.8% female). The MAGGIC risk score and the predicted 1-year mortality rate by the web-based BCN-BioHF and 3C-HF risk calculators were obtained for all patients. Patients were followed for a median duration of 428 days (interquartile range: 208-794 days) to observe all-cause mortality. The predictive value of the risk scores was compared using the area under the curve (AUC) of time-dependent ROC curves for 1-year mortality.

Results:
Complete risk scores and predicted 1-year mortality rates were available for 1,082 (98.8%) patients. The AUC for 1-year mortality prediction was 0.73 (95% CI 0.68, 0.78) for the MAGGIC score, 0.65 (0.59, 0.71) for BCN-BioHF, and 0.71 (0.64, 0.76) for 3C-HF. The MAGGIC score exhibited a significantly higher AUC than BCN-BioHF (p=0.003), while no significant differences were observed between the MAGGIC score and 3C-HF, or between BCN-BioHF and 3C-HF.

Conclusion:
This study demonstrates that the MAGGIC, BCN-BioHF, and 3C-HF risk scores provide good predictive value for 1-year mortality in Japanese patients with HFpEF. The superior performance of the MAGGIC score suggests that considering the ethnic differences in HFpEF pathophysiology is crucial for accurate risk prediction in Asian populations.
Abstract 13991: Sleep Patterns and Quality of Life in Pulmonary Arterial Hypertension
Authors: Hughes Andrew M , Annis Jeffrey , Hemnes Anna R , Lindsey Alisha , Burke Kelly , Brittain Evan ,   PVDOMICS Study Group
Published: December 2023

Introduction:
Data on sleep duration and quality of life (QOL) in PAH are limited to self-reported surveys. Commercial wearables represent a cost-effective, low-burden approach to objectively assess real-world sleep patterns. We aimed to describe sleep patterns and associations with quality of life (QOL) in a cohort of PAH patients.

Methods:
We enrolled patients with expert adjudicated PAH from the NHLBI-funded Pulmonary Vascular Disease Phenomics (PVDOMICS) and compared them with individuals from the All of Us Research Program matched on age, sex, body mass index, and monitoring dates. Sleep variables were measured using Fitbit devices, which patients wore continuously for 12 weeks at baseline and again after 1 year. In PAH patients, QOL (Minnesota Living with Heart Failure (MLHF) survey) was assessed at baseline and 1 year; higher MLHF scores indicate greater impairment.

Results:
We enrolled 36 patients with PAH (48.9 ± 13.2 years, 81% female). Total minutes in bed and total minutes per sleep stage at baseline and 1 year follow-up are shown in
Table 1.
Compared with matched controls, patients with PAH have similar minutes in bed and asleep but markedly reduced minutes of deep (p<0.001) and REM sleep (p <0.001). In the PAH cohort, changes in sleep parameters from baseline to year 1 correlated inversely with changes in MLHF emotional score from baseline to year 1 including: time in bed (r = - 0.61, p = 0.017), total minutes asleep (r = -0.59, p = 0.020), total minutes light sleep (r = -0.53, p = 0.041), and total minutes deep sleep (r = - 0.52, p = 0.047). Minutes of deep and REM sleep over 1 year were inversely correlated with medication escalation over that year (rs = -0.49 and -0.47, p<0.02 for both). No sleep measures correlated with baseline 6-minute walk distance.

Conclusions:
Patients with PAH have poor sleep quality compared to healthy controls. Poor sleep quality may contribute to or result from some of the common symptoms of PAH such as fatigue, mood disorders, and decreased QOL.
Abstract 14162: Long-Term Outcomes for Contemporary Mechanical versus Bioprosthetic Surgical Mitral Valve Replacement in Patients Aged 50 to 70 Years
Authors: Fath Ayman R , Aglan Amro , Eldaly Abdullah , Olagunju Abdulbaril , Almomani Ahmed
Published: December 2023

Background:
Guidelines are still unclear regarding whether mechanical or bioprosthetic valves should be selected for mitral valve replacement (MVR) in patients aged 50-70 years.

Aims:
To assess long-term outcomes in patients aged 50-70 years undergoing MVR using contemporary mechanical and bioprosthetic valves.

Methods:
We performed a retrospective study using the TriNetX global database to identify patients aged 50 to 70 years who had primary isolated surgical MVR from 2014 to 2020. Patients who had concomitant or prior cardiac surgeries were excluded. Patients were stratified into 2 groups: mechanical and bioprosthetic, and a 1:1 propensity-score matching to control for baseline differences between the two groups was performed. The primary endpoint was all-cause mortality and secondary endpoints were stroke, major bleeding, and reoperation over a follow-up period of 8 years.

Results:
Propensity-score matching yielded 1,130 patients in each group. There were significantly higher rates of all-cause mortality, stroke, and major bleeding events in the mechanical group compared to the bioprosthetic valve. There was no significant difference between the two groups regarding reoperation (Table 1 and Figure 1).

Conclusion:
At an 8-year follow-up, the use of contemporary bioprosthetic valves for MVR in patients aged 50-70 years shows favorable all-cause mortality and lower rates of strokes and major bleeding with similar reoperation rates compared to mechanical valves.
Abstract 14202: Vasospastic Angina as a Potential Cause of Post-Acute Sequelae of COVID-19
Authors: Aikawa Tadao , Funayama Naohiro , Minamino Tohru
Published: December 2023

Introduction:
Although evidence-based practice of has progressed, little is known about underlying mechanisms of chest pain symptoms in patients with post-acute sequelae of COVID-19 (PASC) and preferred approaches for their assessment. Several mechanisms underlying COVID-19-related endothelial dysfunction have been proposed. The purpose of this study was to explore the prevalence of vasospastic angina as a cause of chest pain in PASC patients.

Methods:
We retrospectively reviewed 273 consecutive patients who presented to an outpatient unit for cardiovascular PASC between June 2021 and March 2023. After the initial evaluation with electro- and echocardiography, coronary computed tomography angiography or cardiac magnetic resonance imaging were performed to rule out obstructive coronary artery disease and myopericarditis if patients had intermittent chest pain and had no contraindications to these tests. When the patients’ chest pain mainly occurred at night and in the morning or was resolved by nitrates, invasive coronary angiography and acetylcholine provocation testing were performed to diagnose vasospastic angina.

Results:
Eight of 273 patients with PASC underwent acetylcholine provocation testing. The median time from the diagnosis of SARS-CoV2 infection to acetylcholine provocation testing was 197 (interquartile range, 120-542) days. The mean age of the patients was 37.1 years; two required oxygen support during acute COVID-19; and none had previous history of cardiovascular disease (
Figure
). Five of the 8 patients showed acetylcholine-induced multivessel coronary vasospasm and were diagnosed as vasospastic angina. Their chest pain improved with calcium channel blockers and nitrates, whereas nonfatal myocardial infarction occurred in one patient after the diagnosis of vasospastic angina.

Conclusions:
Our observational case series suggest that vasospastic angina should be considered as a potential cause of PASC.
Abstract 14204: Efficacy and Safety of Low-Dose Edoxaban According to Body Weight in Very Elderly Patients With Atrial Fibrillation: A Sub-Analysis of the ELDERCARE-AF Trial
Authors: Akao Masaharu , Yamashita Takeshi , Fukuzawa Masayuki , Hayashi Takuya , Okumura Ken
Published: December 2023

Background:
The ELDERCARE-AF trial showed that low-dose edoxaban is beneficial in elderly patients with non-valvular atrial fibrillation (AF) who are considered ineligible candidates for standard oral anticoagulants (OACs) due to high bleeding risk, but it was not known whether this is the case in low-body-weight patients.

Methods:
This was a prespecified sub-analysis, by body weight (≤45 and >45 kg), of the ELDERCARE-AF trial, a randomized, placebo-controlled trial comparing low-dose edoxaban (15 mg once daily) with placebo. All patients were of Japanese ethnicity and considered ineligible for standard doses of OACs. The primary efficacy endpoint was stroke or systemic embolism (SSE). The key secondary endpoints were all-cause mortality and net clinical outcome. The primary safety endpoint was major bleeding according to the definition of the International Society on Thrombosis and Hemostasis.

Results:
Of the 984 patients, 374 patients (38.0%) were in the ≤45 kg group and 610 (62.0%) patients were in the >45 kg group. The SSE was lower with edoxaban than with placebo in both weight groups (≤45 kg group: hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.16-0.80; >45 kg group: HR 0.31, 95% CI 0.13-0.73; interaction P 0.82). Both all-cause mortality and net clinical outcome were higher in the ≤45 kg group, with no significant difference between treatment groups. Major bleeding was numerically higher with edoxaban than with placebo (≤45 kg group: HR 3.05, 95% CI 0.84-11.11; >45 kg group: HR 1.40, 95% CI 0.56-3.48), with no interaction with body weight (interaction P 0.33). Similar results were obtained in the exploratory analysis of patients divided into four quartiles of body weight (>57.9, >49.0 to ≤57.9, >42.0 to ≤49.0, and ≤42.0 kg).

Conclusions:
The benefit of edoxaban 15 mg was consistent in elderly AF patients with low body weight, provided clinicians remain vigilant about the risk of major bleeding.
Abstract 14235: Alcohol Septal Ablation Using Septal Branches From the Non-Left Anterior Descending Artery Demonstrates Similar Effectiveness Compared to Septal Branches From Left Anterior Descending Artery
Authors: Harano Yoshihiro , Kawase Yoshiaki , Sahashi Yuki , Matsuo Hitoshi
Published: December 2023

Introduction:
Alcohol septal ablation (ASA) is performed on symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy to reduce pressure gradient in the left ventricular outflow tract (LVOT), usually using the major septal branch from the left anterior descending (LAD) artery. In some cases, a septal branch from other than LAD may be selected as an alternative target that perfuses the basal septum. The aim of this study is to evaluate the effectiveness and safety of ASA using non-LAD branches compared to ASA using major branches directly from the LAD.

Methods:
We conducted a single-center, retrospective, observational cohort study comprising patients who underwent ASA between 2011 and 2023. The primary outcome was the success rate, defined as a pressure gradient in the LVOT of less than 30 mmHg one year after ASA. The secondary outcomes were all-cause death, cardiac rehospitalization, and newly-developed conduction system disorders.

Results:
The study enrolled 36 patients (age: 66.6± 12.7 years; 13 men), and pressure gradients in LVOT before ASA were not significantly different in the two groups (76±50 mmHg in the non-LAD group (n =17) vs. 76±39 mmHg in the LAD group (n = 19), p= 0.90). The non-LAD and LAD groups had similar success rates of 88.2 % and 86.7 %, respectively, at one year (p > 0.99). The decrease in the pressure gradient in LVOT was similarly observed in both groups (61±44 mmHg in the non-LAD group vs. 61±35 mmHg in the LAD group, p=0.87). No patient died in either group within one year following ASA. The study found a non-significant incidence of newly-developed conduction system disorder (11.8 % in the non-LAD group vs. 5.3 % in the LAD group, P= 0.92).

Conclusions:
ASA using the non-LAD artery demonstrated similar effectiveness in decreasing the pressure gradient in the LVOT and similar safety compared to using the septal branch from the LAD at one year. Therefore, the non-LAD artery may become an alternative option for the target vessel in ASA.
Abstract 14249: Sex and Gene Based Differences in Age Related Penetrance of Dilated and Arrhythmogenic Cardiomyopathy
Authors: Bart Nicole K , Stroeks Sophie , Khan Sadiya S , Reza Nosheen , Olivotto Iacopo , Vissing Christoffer , Sinnette Corine , Owens Anjali T , Fornaro Alessandra , Mestroni Luisa , Taylor Matthew , Helms Adam S , Prasad Sanjay K , Saberi Sara , Shore Supriya , Verdonschot Job , sinagra Gianfranco , Merlo Marco , Gigli Marta , Wilsbacher Lisa D , Heymans Stephane , Wheeler Matthew , Ashley Euan A , Dal Ferro Matteo , Paldino Alessia , Day Sharlene , de Feria Alejandro , Stevenson Lynne W , Ho Carolyn , Claggett Brian , Ware James S , Parikh Victoria N , Tayal Upasana , Lakdawala Neal K ,   On behalf of the SHaRE investigators
Published: December 2023

Background:
Approximately 40% of cases of dilated (DCM) and arrhythmogenic cardiomyopathy (AC) are caused by rare genetic variants of large-effect. Sex-based differences in the penetrance of genetic DCM and AC have been described, however, findings have been inconsistent. Age at the time of diagnosis can be used as an indicator of age-related penetrance. In this study we aimed to describe differences in age at diagnosis in subgroups of patients with DCM and AC; the latter defined as ventricular arrhythmias preceding or superseding systolic LV dysfunction.

Methods:
Patients with DCM and AC were identified using data from 3 centers participating in the international SHaRe registry. Age at diagnosis and other baseline characteristics were compared across genetic subtypes; including patients with pathogenic and likely pathogenic (LP/P) variants (G+), variants of unknown significance (VUS), without identifiable genetic cause (G-) and subgroups with LP/P variants in 3 genes most frequent in this cohort (
TTN
,
LMNA
, and
DSP
).

Results:
Of 3662 patients with DCM and AC, 1341 were females (37%) and 3551 probands (97%). There were no significant differences in LVEF (38±14 vs. 41±14, p=0.07) or NYHA III-IV symptoms (14% vs. 11%, p=0.2). Genetic testing was performed more frequently in females (27% vs. 22%; p<0.01) but the frequency of LP/P variants did not differ significantly by sex (female 49% vs. male 38%, p=0.07). In the entire cohort, the age of diagnosis did not vary between females and males; however, females with LP/P variants in
TTN
were 9 years older (p<0.01) whereas females with LP/P variants in
DSP
were 10 years younger (p=0.037) at diagnosis than males (figure).

Conclusion:
Sex-based differences in age related penetrance of DCM and AC may differ across disease genes. Increased vigilance is warranted for early presentation of AC. Future research should examine the factors that underlie this heterogeneity and determine associated differences in clinical outcomes.
Abstract 14359: Life’s Essential 8 and Cardiovascular Health of Veterans: The Million Veteran Program
Authors: Nguyen Xuan-Mai T , Li Yanping , Ho Yuk-lam , Houghton Serena , Ivey Kerry , Pyatt Mary , Treu Timothy M , Posner Daniel , Li Ruifeng , RAGHAVAN SRIDHARAN , Gagnon David , Gaziano John , Djousse Luc , WILSON PETER , Cho Kelly ,   VA Million Veteran Program
Published: December 2023

Background and Hypothesis:
The American Heart Association (AHA) recently proposed the Life’s Essential 8 (LE8) score as an enhanced measurement tool for cardiovascular health. No studies to date have estimated its association with the risk for atherosclerotic cardiovascular disease (ASCVD) incidence and prognosis.

Methods:
A prospective cohort study of 384,518 Veterans enrolled in the VA Million Veteran Program (MVP) (2011-2021). LE8 score was developed using AHA guidelines. Primary outcome was total ASCVD. Secondary outcome was hard ASCVD which included non-fatal myocardial infarction, non-fatal stroke, and fatal CVD.

Results:
Based on 1.16 million person-years of follow-up among Veterans with no ASCVD at baseline, 46,295 Veterans had ASCVD events during follow-up. LE8 score was associated with ASCVD and its subtypes in a linear dose-response manner (Figure 1A). The overall population-attributable fractions for all non-ideal LE8 scores was 59% (95%CI: 51%-66%) for ASCVD, where non-ideal blood pressure was most influential (Figure 1B). Based on 0.6 million person-years of follow-up among patients with ASCVD at baseline, the hazard ratio for incident or recurrent hard ASCVD was 0.52 (95%CI: 0.48-0.56) comparing veterans with ≥650 to those with LE8 score <350, with a dose-response linear association pattern.

Conclusions:
Based on 1.76 million person years of follow-up among Veterans, a high LE8 score was associated with a significantly lower ASCVD risk and a lower likelihood of developing adverse cardiovascular events regardless of ASCVD status at baseline. Theoretically, an ideal LE8 could potentially prevent almost 59% of ASCVD in this study. Our results support the importance of AHA’s promotion of LE8.
Abstract 14457: Safety and Effectiveness of P2Y12 Inhibitors in Critically Ill Patients With COVID-19: A Meta-Analysis of Randomized Controlled Trials
Authors: Singh Sahib , Tantry Udaya , Bliden Kevin , Gurbel Paul
Published: December 2023

Introduction:
Critically ill patients with COVID-19 have a high risk of developing thromboembolic events. Randomized controlled trials (RCTs) have shown conflicting results regarding the use of P2Y12 inhibitors in such patients. We conducted a meta-analysis of the available trials.

Methods:
Studies comparing P2Y12 inhibitors vs control in critically ill patients with COVID-19 were searched from online databases. The primary endpoints of interest were myocardial infarction (MI), systemic arterial thromboembolism, deep venous thrombosis (DVT), pulmonary embolism (PE), ischemic stroke, mortality, and major bleeding at the longest available follow up. Random-effects model was used to calculate risk ratios (RR) with 95% confidence intervals (CI).

Results:
Three RCTs, with a total of 2,223 patients - 1,084 in the P2Y12 inhibitor group and 1,139 in the control group were included. The mean age was 57 years and 63% of patients were men. The follow up duration varied from 28 to 90 days. The two groups had similar risk of DVT (RR 0.91, 95% CI 0.65-1.28, p = 0.60), ischemic stroke (RR 2.25, 95% CI 0.91-5.55, p = 0.08), MI (RR 1.37, 95% CI 0.54-3.47, p = 0.50), PE (RR 0.95, 95% CI 0.47-1.95, p = 0.90), systemic arterial thromboembolism (RR 1.20, 95% CI 0.24-6.09, p = 0.82), mortality (RR 0.89, 95% CI 0.77-1.03, p = 0.12) (Figure 1) and major bleeding (RR 1.34, 95% CI 0.47-3.78, p = 0.59) (Figure 2).

Conclusions:
No significant difference was found in venous or arterial thromboembolism, mortality, or major bleeding events in critically ill COVID-19 patients treated with P2Y12 inhibitors as compared to control.