bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13238: Persistence of High Rates of Major Adverse Cardiovascular Events at 1 Year Post-Myocardial Infarction in Patients With Multivessel Disease: A Systematic Literature Review
Authors: Bahit Maria C , Korjian Serge , Daaboul Yazan , Chi Gerald , Jiang Ginger , Libby Peter , Bhatt Deepak L , Reynolds Matthew , Mehran Roxana , Ridker Paul M , Baron Suzanne , Sacks Frank M , Gabriel Susan , Nara Paul , Shaunik Alka , Gibson Charles M
Published: December 2023

Background:
Multivessel disease (MVD) heightens the risk of major adverse cardiovascular events (MACE) in post-myocardial infarction (MI) patients. The risk of MACE is elevated in the early period after an MI, a period unaddressed by current secondary preventative therapies.

Research aims:
To better understand the impact of MVD on clinical and patient-centered outcomes post-MI in the current treatment landscape.

Methods:
A systematic literature review was conducted to identify relevant articles published between March 2019 and July 2022 from MEDLINE, Embase, Cochrane databases, and cardiovascular (CV) and health outcomes conferences. Articles reporting on pre-specified clinical or patient-centered outcomes in post-MI patients with MVD at timepoints within 1 year were included. Studies that included patients with cardiogenic shock were excluded from this review.

Results:
Clinical and patient-centered outcomes were reported in five randomized-controlled trials (RCTs) and 24 observational studies across 30 articles; and one RCT across two articles, respectively. Although the definition of MVD varied, it was generally characterized by ≥50% stenosis in ≥1 noninfarct-related coronary artery. Rates of individual MACE endpoints (all-cause mortality, CV mortality, MI, stroke) were variable (Table), likely due to heterogeneity in study populations and interventions. Nevertheless, a key trend was identified; MACE rates at 1-year post-MI were typically not substantially higher than those at earlier timepoints. EQ-5D scores, reflective of quality of life (QoL), increased following treatment; however, increases were marginal, indicating minimal improvements in QoL.

Conclusions:
MVD is associated with high rates of MACE early after MI that persist at 1 year. Novel therapies that address CV risk in the early period post-MI may support improved CV outcomes among patients with MVD. Further data on patient-centered outcomes are warranted.
Abstract 13239: Atrial Fibrillation Ablation With High-Power Short-Duration Setting Reduces Change in Periprocedural Thrombotic Marker and Suppresses the Onset of Silent Stroke
Authors: Kamioka Masashi , Okuyama Takafumi , Watanabe Tomonori , Watanabe Hiroaki , Makimoto Hisaki , Yokota Ayako , Komori Takahiro , Kabutoya Tomoyuki , Imai Yasushi , Kario Kazuomi
Published: December 2023

Background:
Atrial fibrillation (AF) ablation with high-power short duration (HP-SD) setting has been widely recognized to decrease the procedure time and to improve the ablation outcome.

Hypothesis:
We hypothesized that AF ablation with HP-SD setting can minimize the change in periprocedural thrombotic markers and the risk of silent stroke (SS).

Aims:
The aim of the present study is to investigate the impact of HP-SD setting ablation for AF on thrombotic markers and SS.

Methods:
We enrolled 101 AF patients: HP-SD group (n =67) using 50W; and Conventional ablation group (n = 34) using 30 to 40W. D-dimer, thrombin antithrombin complex (TAT) and total plasminogen activator inhibitor-1 (tPAI-1) were analyzed pre, post and 1 day after procedure. Magnetic resonance imaging was performed 1 day after procedure.

Results:
Left atrial (LA) dwelling time was significantly shorter in HP-SD group (P<0.05). In Conventional ablation group, the D-dimer and tPAI-1 levels continued to increase until 1 day after, while the TAT peaked after the ablation. On the other hand, the range of the variation of these thrombotic markers in HP-SD group was smaller (
Figure 1
). SS occurred more frequently in Conventional ablation group than in HP-SD group (26% vs 4%, P<0.05). In logistic regression analysis, HP-SD setting and TAT difference (post - pre-procedure) remained independent predictor for SS (Odds ratio: 0.141 and 5.838, P<0.05, respectively).

Conclusion:
HP-SD setting was associated with the shorter LA dwelling time and the smaller thrombotic markers change than conventional ablation, which could contribute to the lower prevalence of SS.
Abstract 13243: Different Efficacy of Angiotensin Receptor Blockers for Nocturnal Blood Pressure Reduction in Patients With Mild to Moderate Hypertension: A Systematic Review and Meta-Analysis
Authors: Liu Jing , Chen Wei , Shao Shihuan , Chen Yuanyuan , Wang Hongyi , xi yang , Wang Luyan
Published: December 2023

Introduction:
High nocturnal blood pressure (BP) is correlated with an increased risk of cardiovascular events and is an important predictor of cardiovascular death in hypertensive patients. Thus, nocturnal BP control is of great importance for cardiovascular risk reduction.

Hypothesis:
As the most commonly prescribed BP-lowering agents, angiotensin II receptor blockers (ARBs) maybe have different efficacy for nocturnal BP reduction in patients with mild-to-moderate hypertension (MMH).

Methods:
We conducted a systematic search in PubMed, EMBASE, Cochrane Library and Web of Science from inception to August 8th, 2022, and collected the ambulatory BP study data of different ARBs (allisartan, candesartan, irbesartan, losartan, olmesartan, telmisartan and valsartan) in patients with MMH following PICOs principle. Data was extracted and the risk of bias of the included studies was evaluated accordingly, and R software (version 4.0.0) was used for statistical analysis.

Results:
Seventy-eight studies with 13,108 patients were included. The results of meta-analysis showed that allisartan, olmesartan, telmisartan were associated with greater reduction in nocturnal systolic BP, while valsartan, olmesartan and telmisartan demonstrated greater efficacy in reducing nocturnal diastolic BP. In the aspect of the nocturnal-diurnal BP drop ratio, only allisartan was greater than 1 (figure). Additionally, allisartan showed more advantages in the last 4-6 hours ambulatory BP drop, the proportion of patients with dipping BP pattern, and the 24 hours ambulatory BP drop as compared to other ARBs.

Conclusions:
For patients with MMH, allisartan, olmesartan and telmisartan have more advantages in nocturnal BP reduction among the ARBs, while allisartan can reduce nocturnal BP more than daytime BP and improve the dipping pattern, contribute to restore normal BP rhythm.
Abstract 13245: Neural Network-Derived Electrocardiographic Features Predict Future Cardiovascular Disease and All-Cause Mortality
Authors: Sau Arunashis , Ribeiro Antonio , McGurk Kathryn A , Pastika Libor , Bajaj Nikesh , Ardissino Maddalena , Chen Jun Yu , Wu Huiyi , Shi Xili , Hnatkova Katerina , Zheng Sean , Britton Anne , Shipley Martin J , Andršová Irena , Novotny Tomas , Sabino Ester Cerdeira , Giatti Luana , Barreto Sandhi Maria , Waks Jonathan W , Kramer Daniel B , Mandic Danilo , Peters Nicholas S , O'Regan Declan , Malik Marek , Ware James S , Ribeiro Antonio , Ng Fu Siong
Published: December 2023

Background
Subtle prognostically-important ECG features may not be apparent to physicians. In the course of supervised machine learning (ML), many thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology.

Hypothesis:
Novel neural network (NN)-derived ECG features can predict future cardiovascular disease and mortality

Methods and Results:
We extracted 5120 NN-derived ECG features from an AI-ECG model trained for six simple diagnoses and applied unsupervised machine learning to identify three phenogroups. In the derivation cohort (CODE, 1,558,421 subjects), the three phenogroups had significantly different mortality profiles. After adjusting for known covariates, phenogroup B had a 20% increase in long-term mortality compared to phenogroup A (HR 1.20, 95% CI 1.17-1.23, p < 0.0001). The predictive ability of the phenogroups was retained in a group with physician confirmed normal ECGs. We externally validated our findings in five diverse cohorts (Figure) and found phenogroup B had a significantly greater risk of mortality in all cohorts. Phenome-wide association study (PheWAS) showed phenogroup B had a higher rate of future AF, ischaemic heart disease, AV block, heart failure, VT and cardiac arrest. Phenogroup B had increased cardiac chamber volumes and decreased cardiac output. A single-trait GWAS yielded four loci. SCN10A, SCN5A and CAV1 have roles in cardiac conduction and arrhythmia. ARHGAP24 does not have a clear cardiac role and may be a novel target. Gradient-weighted Class Activation Mapping (Grad-CAM) identified the terminal QRS and terminal T wave as important regions of the ECG for identification of phenogroup B.

Conclusion:
NN-derived ECG features can be used to predict all-cause mortality and future cardiovascular diseases. We have identified biologically plausible and novel phenotypic and genotypic associations that describe mechanisms for the increased risk identified.
Abstract 13262: A Self-Administered Home Inotrope Program for Unfunded Patients With End-Stage Heart Failure
Authors: Hendren Nicholas , carter spencer , Mathew Chris , Alvarez Kristin , Truby Lauren K , Farr Maryjane , Das Sandeep R
Published: December 2023

Introduction:
Uninsured patients with inotrope-dependent end-stage heart failure (HF) pose a formidable challenge to the healthcare system and innovative solutions are required. We created a health system funded home program for palliative and bridge-to-funding inotrope strategies for unfunded patients. Herein, we report our updated experiences.

Methods:
We reviewed records of all patients enrolled in the home inotrope program since inception in 2019. Patients must have demonstrated a low cardiac index that was stabilized on a single inotrope. Advanced HF and palliative care consultations are mandatory. Next, a multidisciplinary team educates the patient via a teach-teach back method on how to self-administer intravenous inotropes via a provided continuous infusion pump. After discharge, patients attended weekly clinic appointments for assessment and dressing changes. Clinic appointments, supplies, and medications are provided by the health system at minimal cost to the patient. This project was deemed IRB exempt as a quality improvement project.

Results:
Thus far the program has enrolled 15 uninsured patients through April 24, 2023 (table). The median duration of inotropic support was 70 (32-143) days. Patients remained at home for 90% of the 1500 total supported days. To date, one patient has received a heart transplant and three patients have received LVAD surgery after obtaining health insurance. Three (20%) patients experienced a catheter-associated infection, with two developing bacteremia. All patients endorsed satisfaction with increased time spent outside of the hospital. This was estimated to have saved >$2,363,000 in self-pay discounted charges for a general care telemetry bed and >$586,000 in professional charges (CPT 99233, estimates via price transparency act).

Conclusion:
A self-administered home inotrope program for select patients is feasible, safe, and cost-effective. It may also serve as a bridge to funding for advanced therapies.
Abstract 13263: Utilization of Proteomic Surrogates for Early Detection of Unexpected Drug Benefits
Authors: Chadwick Jessica , Hinterberg Michael , Paterson Clare , Shrestha Sama , Simpson Missy , Troth Emma , Williams Stephen A
Published: December 2023

Introduction:
Detection of benefits and adverse effects of therapies in early clinical trial phases could improve the safety, efficiency, and cost of clinical trials. For example, while SGLT2i and GLP-1 RA drugs are recognized success stories, earlier identification of their benefits beyond improved diabetic control may have had the potential to save loss of patients’ lives and years of sales.

Hypothesis:
Using the EXSCEL and SUGAR-DM-HF trials as examples to study GLP1-RA and SGLT2i responses, we hypothesized that previously validated proteomic surrogates of cardiovascular (CV) events, and kidney health could have enabled detection of these unexpected drug benefits earlier in development in a smaller number of participants over a shorter follow-up period.

Methods:
CV risk and kidney prognosis SomaSignal tests (each derived from ~5000 plasma proteins measurements using SomaScan® assay) were applied to paired plasma samples at baseline and 9-months (SUGAR-DM-HF) or 1-year (EXSCEL) in intervention (EXSCEL n=1840; SUGAR-DM-HF n=45) and control (EXSCEL n=1833; SUGAR-DM-HF n=52) participants. Power calculations were performed to determine the minimum number of samples needed to detect a significant change within the treatment period with alpha = 0.05, 80% power using a t-test comparing two-sample means.

Results:
We demonstrated that the cardiovascular benefits of exenatide were detectable with a proteomic surrogate within 1-year (p=0.002), with power analysis indicating a significant 1-year change is observable with group sizes of n=1368 compared with >7000 participants for up to 6.8 years follow-up. Additionally, kidney protection (p=0.037) and CV protection (p=0.06) impacts of empagliflozin within 36 weeks were detectable using proteomic surrogates in small sample sizes (n ~ 50) compared to published outcomes studies requiring thousands of participants followed for >2 years.

Conclusions:
SomaSignal tests were able to predict cardiometabolic benefits of GLP-1 RA and SGLT2i drugs within a significantly shortened interval and fewer participants than in the outcome trials. Proteomics may provide a powerful tool for improving the efficacy, and cost of drug development by predicting effects of novel therapeutics in smaller, shorter studies.
Abstract 13269: Clinical and Electrophysiological Features of New Onset Ventricular Arrythmias Following Catheter Ablation of Atrial Fibrillation
Authors: Ahmed Adnan , Bawa Danish , Tummala Rangarao V , Darden Douglas J , Koerber Scott , Kabra Rajesh , Gopinathannair Rakesh , Lakkireddy Dhanunjaya , Pothineni Naga Venkata
Published: December 2023

Introduction:
Data on new onset ventricular arrhythmias (VAs) following catheter ablation of atrial fibrillation (AF) is sparse.

Hypothesis:
We aimed to assess the incidence of new onset VA post AF RFA.

Methods:
We conducted a retrospective study of all patients at our institution that underwent AF ablation who also developed symptomatic high burden premature ventricular complexes (PVCs) requiring catheter ablation within 1 year of the index AF ablation procedure. All patients underwent post AF ablation monitoring with either 48 hr Holter monitors or implantable cardiac monitors. New onset VA was defined as symptomatic new onset PVC with >5% burden. Data on PVC morphology and successful ablation sites was analyzed.

Results:
Out of 175 patients that underwent AF ablation during the study period, 2.8 % (n=5) patients developed new onset high burden PVCs requiring catheter ablation therapy within 1 year of AF ablation. Mean age was 68.6
+
11 years and all patients were male. Mean baseline LVEF was 56
+
9.6% and mean PVC burden was 10.3
+
8.8 %. A total of 9 PVCs were mapped in 5 patients. The number of VA morphology was 1 in 2 (40%) patients, 2 in 2 (40%) and 3 in 1 (20%) patient. Site of origin for the PVCs was in the left ventricle in all patients, with majority (55%) localizing to the LV outflow tract and summit region (table). Average time from AF RFA to PVC ablation was 4
+
2.9 months. PVC ablation was successful in all patients except one where ablation was deferred due to proximity to the conduction system.

Conclusions:
New onset VAs following catheter ablation of AF tend to localize to the LV outflow tract and areas of bipolar voltage abnormality. Potential mechanisms of new onset PVCs could include altered sympathetic tone due to ablation of cardiac ganglia, unmasking of PVCs due to regularization of ventricular rate and withdrawal of anti-arrhythmic medications. Further prospective studies are needed to understand true incidence of new onset VAs following AF ablation.
Abstract 13272: Acute Effects of Enhanced External Counterpulsation in Adults With Fontan Circulation
Authors: Wu Fred M , Misra Amrit , Valle Christopher , Duncan Madeline E , Ghelani Sunil J , Gerhard-Herman Marie D , Lipsitz Stuart R , Rathod Rahul H , Gurvitz Michelle Z , Singh Michael N , Valente Anne M
Published: December 2023

Background:
Patients who have undergone Fontan palliation for single ventricle CHD exhibit reduced cardiac output.

Aims:
To study the safety and acute hemodynamic effects of enhanced external counterpulsation (EECP) in a cohort of Fontan patients.

Methods:
Pilot study of adult Fontan patients recruited through the ambulatory clinic at a single, large-volume ACHD center. Patients underwent TTE and measurement of pulmonary blood flow (PBF), a surrogate for cardiac output, followed by 1 hour of EECP divided into 20-minute stages (80 mmHg, 160 mmHg, 240 mmHg). TTE and PBF measurement were repeated at each stage and 15-30 minutes after completion of EECP. Patients were monitored for symptoms throughout the visit. A repeated measures linear-mixed-model (robust to non-normality) was used to estimate the mean at each time point and to test for differences across time points.

Results:
There were 23 patients enrolled (52% male, 91% cis-gender, 74% White). Mean age at enrollment and at Fontan completion was 33.0 ± 7.8 years and 5.1 ± 4.1 years, respectively. Six patients (26%) had a pacemaker. Twenty-two (96%) completed a full hour of EECP. Pressure was reduced in the third stage for 3 patients due to discomfort. No patients reported chest pain or increased dyspnea during EECP. PBF was increased at each stage of EECP compared to baseline and returned to baseline post-EECP (Fig. 1). There was a small qualitative improvement in ventricular systolic function in the second and third stages of EECP compared to baseline (160 mmHg: p=0.048; 240 mmHg: p=0.024). O
2
saturation was increased at each stage of EECP compared to baseline (baseline: 93.0%, 80 mmHg: 94.3% [p=0.008], 160 mmHg: 94.6% [p=<0.001], 240 mmHg: 94.6% [p=<0.001]). Mean arterial pressure and heart rate did not change.

Conclusions:
EECP is well-tolerated in adult Fontan patients and acutely improves PBF at pressures as low as 80 mmHg. Further study is warranted to explore long-term therapeutic effects of EECP in these patients.
Abstract 13285: Association Between Adverse Childhood Experiences and Sleep Duration in Children: Utilizing 2018 to 2021 National Survey of Children’s Health
Authors: Song Minkyoung , Dieckmann Nathan F , McHill Andrew W , Musil Carol M , Hayman Laura L
Published: December 2023

Background:
Adverse childhood experiences (ACEs) and short sleep duration are both negatively associated with cardiovascular health. However, there is limited knowledge on the association between ACEs and sleep duration in children.

Objective:
We investigated if sleep duration was associated with the number of reported ACEs. We also evaluated the trends in sleep duration among U.S. children over the 4-year period (2018-2021).

Methods:
We used data from the 2018-2021 National Survey of Children’s Health. Based on the American Heart Association (AHA) Life Essential 8 scoring algorithm, we calculated a score for sleep duration (range 0 [lowest] to 100 [highest]). Participants were categorized into three subgroups: (1) meeting age-appropriate
optimal
sleep duration; (2) ≥1-<2 hour below or ≥ 1 hour above optimal sleep duration; and (3) ≥ 2 hours below optimal sleep duration. We employed multinomial logistic regression to assess the association of sleep duration with a cumulative count of ACEs. Secondarily, we examined trends in sleep duration from 2018 to 2021. We controlled for child’s sex, age, race/ethnicity, household poverty level, regular bedtime, physical activity, and caretaker’s level of education.

Results:
Among children aged 6 to 17 years in the 2018-2019 (n=42,141) and 2020-2021 (n=58,964) surveys, the mean sleep duration score was 76.5 (95% CI 75.8 to 77.2) and 77.2 (95% CI 76.6 to 77.9), respectively. The proportion of the children meeting age-appropriate optimal sleep scores increased from 64.5% in 2018-2019 to 65.9% in 2020-2021 (p<0.001). Adjusting for covariates, for each additional ACE the likelihood of having suboptimal sleep duration increased (relative risk ratios: 1.08 [95% CI 1.04 to 1.11] for category (2); 1.26 [95% CI 1.21 to 1.31] for category (3) in 2020-2021. Results were nearly identical in 2018-2019.

Conclusions:
Our findings show that over one third of U.S. children, as assessed using the AHA’s Life Essential 8 scoring criteria, do not meet optimal sleep duration standards and that number of ACEs is associated with suboptimal sleep duration. Findings highlight the importance of screening for ACEs and for sleep insufficiency in childhood with the aim of promoting optimal life course sleep patterns and cardiovascular health.
Abstract 13305: Energetic Basis of Recovered Ejection Fraction in Human Heart Failure
Authors: Goldenberg Joseph R , Hays Allison , Gabr Refaat , Schar Michael , Samuel T. Jake , Gerstenblith Gary , Bottomley Paul A , Weiss Robert G
Published: December 2023

Introduction:
Left ventricular ejection fraction (LVEF) improvement in HFrEF patients is classified as heart failure with improved ejection fraction (HFimpEF) and is associated with better long-term outcomes than persistent HFrEF. HFimpEF is difficult to predict and underlying mechanisms remain poorly understood.

Hypothesis:
Better myocardial high-energy phosphate metabolism at baseline predicts future LVEF recovery and outcomes in a general HFrEF population

Methods:
We measured cardiac energetics, the ratio of the two main high-energy phosphates, phosphocreatine and ATP (PCr/ATP), and the rate of ATP synthesis through the primary cardiac energy reserve reaction creatine kinase (“CK flux”), in 37 nonischemic HFrEF patients (LVEF ≤40%) with
31
P cardiac magnetic resonance spectroscopy (MRS) at 3T. Baseline transthoracic echocardiogram (TTE) was obtained prior to
31
P MRS and follow-up consecutive TTEs with the two highest LVEFs meeting HFimpEF criteria (LVEF >40% and ≥10% increase over baseline LVEF) over a median follow-up of 6.9 years were averaged and used to classify HFimpEF.

Results:
There were no significant differences in demographics, HF etiology, baseline TTE metrics, or medications between persistent HFrEF (n=22) and eventual HFimpEF (n=15). Cardiac CK flux was significantly higher at baseline in patients who later recovered to HFimpEF than in those who remained HFrEF (p=0.031). Better baseline cardiac CK flux was associated with increases in LVEF (p=0.025) and decreases in LV end-diastolic diameter (p=0.016) over time. By both dichotomous and continuous metrics, better preserved CK flux was associated with future HFimpEF. Fourteen subjects (38%), all persistent HFrEF, experienced cardiac death, transplant, or LVAD and had significantly lower baseline CK flux than outcome-free patients (p=0.017). Cardiac PCr/ATP was not associated with eventual HFimpEF, outcomes, or changes in TTE indices.

Conclusion:
Better preserved cardiac CK flux is associated with future LVEF recovery and LV reverse remodeling while lower CK flux is associated with worse cardiac outcomes in HFrEF patients. Interventions restoring CK flux, and possibly other energy-generating metabolic reactions, may elicit myocardial recovery in HFrEF patients.
Abstract 13338: Intravenous Iron for Patients With Iron Deficiency and Acute or Chronic Heart Failure, a Meta Analysis
Authors: K. Awad Ahmed , Abdeljalil Mahmoud Shabaan , Mouffokes Adel , Elbadawy Merihan A , K. Awad Ayman , Nabeel Ambreen , Gardezi Syed Karam , Awan Rehmat Ullah
Published: December 2023

Iron deficiency is very common in heart failure (HF), both with preserved and reduced ejection fraction (HFp/rEF); and has significant impact on both symptoms and prognosis. This review highlights the effect of use of intravenous iron (IVI) therapy in patients with HFrEF

Several databases were searched to identify RCTs that investigate the efficacy and safety of IVI therapy in patients with acute or chronic HF. A meta-analysis was performed using RevMan using random effect model. We used the odds ratio (OR) and mean difference (MD) for dichotomous and continuous outcomes, respectively presented with the corresponding 95% confidence interval (CI).

A total of 18 studies were included with 3,436 patients with mean age of 68 years old. There was no statistically significant difference between IVI and placebo in terms of cardiovascular death or all-cause hospital admission. However, IVI was associated with statistically significant lower risk for hospitalization for any cardiovascular disorder and all cause death with OR 0.42 [95% CI 0.28, 0.64, p<0.0001] and 0.61 [95% CI 0.39, 0.96, p=0.03], respectively. Additionally, there was statistically significant variation in serum ferritin and serum transferrin from baseline favoring intravenous iron with MD -189.62 [95%CI -236.55, -142.69, p=0.01], and -7.65 [95% CI -13.43, -1.87, p=0.009], respectively. Furthermore, IVI was associated with a significant improvement in HF patients’ functional status, evaluated by both Kansas City Cardiomyopathy Questionnaire (KCCQ), and changes from baseline in left ventricular ejection fraction (LVEF) with MD -7.14 [95% CI -10.52, -3.76, p<0.0001], and 3.76 [95% CI 2.32, 5.21, p<0.00001], respectively.

Our meta-analysis demonstrated the capability of IVI to improve clinically meaningful outcomes as HF-related cardiovascular-related hospitalization as well as functional status; however, intravenous iron showed no difference in term of mortality.
Abstract 13339: Proteomic Associations of Cardiac Function Trajectories Through Mid- to Late Life
Authors: Reimer Jensen Anne Marie , Ross James , Lamberson Victoria , Hall Michael E , Matsushita Kunihiro , Lennep Brandon , Lutsey Pamela L , Biering-Soerensen Tor , Shah Amil M
Published: December 2023

Introduction:
Using a novel Bayesian nonparametric modeling approach based jointly on LVEF and E/A ratio, we previously identified 3 trajectories of cardiac function through mid- to late life that associated with heighted risk of incident heart failure (HF): trajectory 1 demonstrated failure to increase LVEF with age; trajectory 2 had progressive LVEF decline; and trajectory 3 had steeper than expected rise in E/A ratio. Trajectories 1 and 2 associated with higher risk of HFrEF while trajectory 3 associated with HFpEF. Whether circulating proteins differ between trajectories is unknown.

Methods:
We assigned 4,419 HF-free participants with available proteomic data (SomaScan v4) at study Visit 5 of the Atherosclerosis Risk in Communities study to their most likely trajectory (2,201 trajectory 1, 162 trajectory 2, 348 to trajectory 3). Associations of plasma proteins with trajectory membership were assessed using multinominal logistic regression analyses adjusted for age and sex at a false discovery rate <0.05. Two-sample Mendelian randomization (MR) was performed to assess potential causal effects between trajectory-associated proteins and LV volume and LVEF.

Results:
Mean age was 75±5 years and 58% were women. Several unique and shared proteins associated with each high-risk trajectory (Figure). MR identified potential causal effects of 13 trajectory-associated proteins on LV volume and LVEF. These included trajectory 3-associated proteins (B3GNT2, MFAP4) with genetically higher levels associated with smaller LV size and higher LVEF, consistent with the observed association with HFpEF. One trajectory 1-associated protein (HADH) had MR association with lower LVEF, consistent with the observed association with HFrEF.

Conclusions:
A Bayesian nonparametric model using multidimensional imaging data identifies trajectories of cardiac function with distinct proteomic associations, a subset of which have potential causal effects on cardiac function.
Abstract 13344: Differential Impact of Self-Care Behaviour on Mortality Between Patients With Stable and Recent Worsening Chronic Heart Failure
Authors: Koya Taro , Nagai Toshiyuki , Tada Atsushi , Nakao Motoki , Ishizaka Suguru , Mizuguchi Yoshifumi , Hiroyuki Aoyagi , Imagawa Shogo , Yusuke Tokuda , Kato Yoshiya , Takahashi Masashige , Hiroto Sakai , Machida Masaharu , Matsutani Kenichi , Saito Takahiko , Okamoto Hiroshi , Anzai Toshihisa
Published: December 2023

Backgrounds:
Although self-care is crucial to maintain health and recommended in the guidelines in patients with chronic heart failure (CHF), its prognostic significance is controversial. We hypothesized that self-care is more effective in vulnerable patients with recent hospitalization due to worsening HF (WHF). The aim of this study was to investigate the prognostic significance of self-care behaviour on mortality between patients with stable and recent worsening CHF.

Methods:
We prospectively examined consecutive 1,873 CHF patients from a Japanese multicenter registry and assessed the European Heart Failure Self-care Behaviour Scale (EHFScBS) at enrollment. The patients were divided into inpatient due to WHF (WHF group) and outpatient stable CHF (stable CHF group). The optimal EHFScBS was defined as more than 70 based on previous reports. The primary outcome was all-cause death.

Results:
Of studied patients (1,102 male, mean age 72 ± 13 years), 625 (33%) and 1,165 (67%) were classified into WHF and stable CHF groups, respectively. During a median follow-up period of 427 (IQR 273 - 642) days, the primary outcome occurred in 50 patients. In stable CHF group, there was no significant difference on primary outcome between optimal and suboptimal EHFScBS (P = 0.65) (Figure A). On the other hand, patients with suboptimal EHFScBS showed a higher incidence of death than those with optimal score in WHF group (P = 0.01) (Figure B). In WHF group, Cox regressions showed that the EHFScBS score was independently associated with mortality (HR 0.51, 95% CI 0.26-0.99) adjusted for significant covariates including hemoglobin, estimated glomerular filtration rate, serum sodium, log NT-proBNP, and the Meta-Analysis Global Group in Chronic Heart Failure risk score.

Conclusions:
In patients with recent worsening, not stable CHF, the EHFScBS was associated with subsequent mortality, indicating that the self-care education might be more effective for patients with recent worsening CHF.
Abstract 13350: Bivalirudin versus Heparin in Patients With Myocardial Infarction, an Updated Meta-Analysis
Authors: Khaity Abdulrhman , Mostafa Al-dardery Nada , Abd-Alwahed Aya Ehab , K. Awad Ahmed , K. Awad Ayman , Nabeel Ambreen , Gardezi Syed Karam , Awan Rehmat Ullah
Published: December 2023

Bivalirudin and heparin are anticoagulant drugs commonly used in patients with acute myocardial infarction who undergo percutaneous coronary intervention (PCI). We performed this meta-analysis to update the present evidence about the safety and efficacy of bivalirudin versus heparin in myocardial infarction patients who underwent PCI. We searched PubMed, Web of Science, Cochrane Central Register of Controlled Trials, and Scopus for relevant randomized controlled trials (RCTs) from inception until 1 April 2023. Records were screened for eligible studies, and all relevant outcomes were pooled as the risk ratios (RR) with the corresponding 95% confidence intervals (CI) in the meta-analysis models using Review Manager (RevMan version 5.4). Pooling data from 9 RCTs (20,036 patients) showed that bivalirudin was superior to heparin in terms of adverse major cardiovascular and cerebrovascular events (MACE) (RR 0.78, 95% CI 0.62 to 0.99, P=0.04) and stent thrombosis (RR 0.73, 95% CI 0.60 to 0.89, P=0.002). However, the overall effect did not favor either of the two groups in terms of all-cause death (RR 1.09, 95% CI 0.90 to 1.30, P=0.37), myocardial infarction (RR 0.87, 95% CI 0.71 to 1.07, P=0.2), stroke (RR 1.09, 95% CI 0.77 to 1.54, P=0.6), bleeding (RR 0.97, 95% CI 0.88 to 1.07, P=0.5), and Bleeding Academic Research Consortium (BARC) scale type 2 (RR 0.93, 95% CI 0.82 to 1.06, P=0.3). Ultimately, the current evidence suggests that bivalirudin appears to be an effective alternative to heparin for anticoagulation during PCI in myocardial infarction patients in terms of MACE and stent thrombosis. Further research is needed to determine the optimal anticoagulation strategy.
Abstract 13352: The Impact of Machine Learning Models in Reducing Variants of Uncertain Significance in Individuals From Underrepresented Populations Who Are Undergoing Genetic Testing for Heritable Heart Conditions
Authors: Morales Ana , Johnson Britt , Facio Flavia , Ting Yi-Lee , Vatta Matteo , Fresard Laure , McKnight Dianalee , Kobayashi Yuya , Reuter Jason , Aradhya Swaroop , Nykamp Keith , Colavin Alexandre
Published: December 2023

Introduction:
Many missense variants remain categorized as variants of uncertain significance (VUS) due to limited evidence. VUS are at the core of disparities, as underrepresented individuals tend to receive more VUS. To improve variant classification (VC) across race, ethnicity and ancestry (REA) groups, we developed machine learning (ML) models by leveraging genomic datasets. For this study, we evaluated the impact of ML-informed VC for cardiomyopathy, arrhythmia, lipidemia, aortopathy, hereditary hemorrhagic telangiectasia, and pulmonary hypertension genes.

Research Question:
What is the utility of ML models for cardiovascular disease panel testing VC across REA groups?

Methods:
From 1/1/2022 to 5/22/2023, ML algorithms that leveraged SpliceAI, gnomAD, AlphaFold and others were validated. ML evidence that met a negative or positive predictive value >80% was incorporated into Sherloc, an ACMG/AMP-based VC framework. At least 1 validated model was available for 225 genes. Analyses of >20,000 patients were performed from random sampling of 20,000 patients with extrapolation. Measurement error was less than 2% variation by bootstrapping. VCs impacted by ML were evaluated, stratified by REA.

Results:
Out of 113,206 (32% were from an underrepresent group) US-based individuals that underwent panel genetic testing, ~65,900 (58%) had ML evidence applied to at least 1 variant. ML contributed to classifying at least 1 benign/likely benign (B/LB) variant in ~33,200 (29%) and at least 1 pathogenic/likely pathogenic (P/LP) variant in ~2,700 (2.4%) individuals. A higher percentage of Asian (43%), Black (42%), and Hispanic (37%) individuals had an ML-dependent definitive VC (P/LP or B/LB) relative to White (28%) individuals by a one-tailed, two-sample proportion test (p<2.0x10
-58
).

Conclusions:
ML modeling demonstrated utility in cardiology diagnostic gene panel testing. Among individuals who had at least 1 variant with ML evidence applied, 54% resulted in definitive classifications. Additionally, ML appears to provide more definitive VCs for underrepresented individuals. ML can assess factors in ways that are agnostic to population ancestry and, when appropriately incorporated into VC, can narrow the VUS gap rates across REA groups.
Abstract 13366: Effectiveness and Safety of Short-Term Outpatient Amiodarone Followed by Catheter Ablation in Management of Atrial Fibrillation
Authors: Adhikari Shubash , Arisha Mohammed , Ezaldin Shady , Annie Frank , Assal Chafik
Published: December 2023

Introduction:
Atrial fibrillation (AF) is the most common arrythmia with significant health system burden and emergency room/hospital admissions. We conducted this study to understand the efficacy of managing AF with first line short term outpatient amiodarone followed by catheter ablation (pulmonary vein isolation). Amiodarone was continued for 6 months post catheter ablation (CA). We looked at a primary end point of recurrence of AF and the drug side effects during the year post CA.

Hypothesis:
If this strategy of short-term amiodarone with early ablation of AF is effective, then we could incorporate this in an AF management care plan.

Methods:
In this retrospective cohort study, we used TriNetX database to collect data on patients with amiodarone initiation with CA and those who were given Dofetilide or Sotalol, followed by CA. We collected data between March 1, 2020, and June 1, 2021. We created a propensity score matching of a 1:1 to match on the covariates: Age, Male, Female, CAD, Heart Failure, Diabetes, COPD, BMI. The endpoint is occurrence of AF within 365 days of medication initiation.

Results:
A total of 40,640 patients were included in the analysis. Of those patients, Cohort 1 comprised amiodarone initiation with catheter ablation (n=176) compared to Dofetilide or Sotalol which had (n=40,474). After the propensity match, we included 176 individual patients in each cohort. The amiodarone group had more men (79.5% vs 58.8, P<0.001) and were with higher comorbidities of CAD, Heart Failure, Diabetes, COPD. At 365 days Amiodarone group had a reduction of 12.6%, P<0.001 of AF compared to Dofetilide or Sotalol patients. There has been no reported side effects requiring discontinuation of Amiodarone.

Conclusions:
We are excited to report a statistically significant 12.6% reduction in AF recurrence in Cohort 1 with short term outpatient Amiodarone initiation with CA compared to inpatient Dofetilide or Sotalol initiation with CA. There have been no safety issues with Amiodarone use for 6-12 months post PVI. This strategy avoids occupying beds for initiation of class III antiarrhythmic (Dofetilide or Sotalol), thus significantly reducing the burden on the health system.
Abstract 13367: Plasma Lipidomic Markers of Diet Quality Are Associated With Risk of Coronary Heart Disease in American Indians
Authors: Wen Xiaoxiao , Fretts Amanda M , Miao Guanhong , Malloy Kimberly , Zhang Ying , Umans Jason G , Cole Shelley A , Best Lyle G , Fiehn Oliver , Zhao Jinying
Published: December 2023

Background:
Diet quality can affect lipid profiles and subsequent risk of coronary heart disease (CHD). Identifying lipidomic markers of diet quality is needed to inform the development of biomarkers of diet, and to understand the mechanisms driving the diet-CHD relation.

Objective:
To identify lipidomic markers of diet quality and examine whether these lipids are associated with incident CHD.

Methods:
We studied 1,694 American Indians (aged 18-75, 62% women) who were free of CHD and had lipidomic and dietary data at baseline (2001-2003). Participants were followed for development of CHD through 2020 (mean follow-up: 17.8 years; total incident cases of CHD: 147). Information on past year diet was collected using the Block Food Frequency Questionnaire, and diet quality was assessed using the Alternative Healthy Eating Index-2010 (AHEI). Mixed effects linear regression was used to identify individual lipid species associated with AHEI at baseline. Cox frailty model was used to estimate the hazard ratio of each AHEI-related lipid for CHD risk. All models adjusted for age, sex, center, education, BMI, smoking, alcohol drinking, level of physical activity, energy intake, diabetes, hypertension, and use of lipid-lowering drugs.

Results:
Among 1,542 lipid species measured, 71 lipid species (23 known) were associated with AHEI at FDR<0.05. Of these, 10 lipids (5 known) were associated with incident CHD
(Figure 1
). The 5 known lipids associated with incident CHD were CE(22:5) B, PC(p-14:0/22:1)/PC(o-14:0/22:1), PC(p-38:3)/PC(o-38:4) B, PE(p-18:0/20:4)/PE(o-18:0/20:4), and SM(d36:2) A. On average, per standard deviation increase in the baseline level of these lipids was associated with 17%-23% increased risk of CHD. These AHEI-related lipids are enriched in glycerophospholipid metabolism.

Conclusion:
We identified lipidomic markers of diet quality in American Indians. Some diet-related lipids are associated with risk of CHD beyond established risk factors.
Abstract 13379: Guideline Directed Medical Therapy Treatment Patterns and Outcomes in Cardiac Sarcoidosis Patients With Systolic Heart Failure
Authors: Sykora Daniel , Elwazir Mohamed , Young Katie , Kolluri Nikhil , Abou-Ezzeddine Omar F , Bois John , Giudicessi John , Cooper Leslie T , Rosenbaum Andrew
Published: December 2023

Introduction:
Cardiac sarcoidosis (CS) results in HFrEF, but its natural history and response to GDMT remains uncertain.

Methods:
We queried a registry of 631 CS patients evaluated at our institution to identify those with LVEF < 35% on TTE within 30 d of diagnosis and a follow-up TTE 12-18 months later (external CS diagnoses were excluded). Demographics, LVEF, NT-proBNP, GDMT, immunosuppression, CIED, and outcomes (hyperkalemia, LVAD/transplant, CV hospitalization, death) were recorded.

Results:
Overall, 25/631 (4%) of CS patients had an LVEF <35% at initial presentation (36% female, 84% white; median age of 58 y; probable/not biopsy-proven CS in 52%). Mean baseline LVEF was 27% (σ=7%), NT-proBNP 1736 pg/mL (n=11), potassium 4.3 mEq/L (n=18), and median NYHA Class II (54%). Patients were on a mean 1.7 GDMT agents at CS diagnosis (Figure). Most were treated with immunosuppression (88%) for mean 0.75 y, usually prednisone (88%, mean 16 mg daily) and fewer with mycophenolate (32%, mean 1875 mg daily), methotrexate (28%, mean 18mg weekly), or TNF-α inhibitor (4%). 64% were on trimethoprim-sulfamethoxazole prophylaxis. At follow-up (median 317 d), 3 patients (12%) required LVAD and 1 (4%) required heart transplant. Mean LVEF improved to 37% (excluding LVAD/transplant, σ=11%, p=0.001). CIED prevalence increased from 48 to 81% (p=0.03). Overall GDMT did not change (mean 2.0 agents, p=0.2) and only beta-blocker dose changed (64 to 138 mg mean daily metoprolol equivalents). Potassium did not change (p=0.4) and hyperkalemic events were infrequent (16%). No patients died, but unplanned hospitalization occurred in 36% of patients.

Conclusions:
CS patients with HFrEF are usually on partial GDMT at diagnosis, presumably due to earlier recognition of HFrEF, but intensification of GDMT may be limited. Despite improved LVEF which may be due to GDMT, immunosuppression, and/or CIED, over 1/3 patients were hospitalized within 18 mo, highlighting the high-risk profile of HFrEF in CS.
Abstract 13402: Outcomes of Cardiac Resynchronization Therapy in Ischemic versus Non-Ischemic Cardiomyopathy: A Patient-Level Meta-Analysis of 7 Randomized Clinical Trials
Authors: Sudesh Saurabh , Abraham William T , Cleland John G , Curtis Anne B , Friedman Daniel , Gold Michael R , Kutyifa Valentina , Linde Cecilia M , TANG Anthony L , Olivas-Martinez Antonio , Inoue Lurdes , Schmidler Gillian , Al-Khatib Sana M
Published: December 2023

Background:
Data on whether CRT results in better clinical and echocardiographic outcomes in patients with NICM versus patients with ICM are conflicting.
Objective:
To determine if there are differences in clinical and echocardiographic outcomes of CRT in patients with ICM versus NICM.

Methods:
We analyzed patient-level data from 7 CRT trials (MIRACLE, MIRACLE-ICD, MIRACLE-ICD II, COMPANION, RAFT, MADIT-CRT, REVERSE) using Bayesian Hierarchical Weibull survival regression modeling, adjusted for baseline characteristics and presence of an ICD, to determine the effect of etiology of cardiac dysfunction on time to all-cause mortality alone and in combination with heart failure hospitalization (HFH). Kaplan-Meier (KM) survival curves were developed with unadjusted frequentist analyses. Linear regression was used to assess the effect of etiology of cardiomyopathy on echocardiographic measurements.

Results:
Of the 6252 patients included, 1535 (25%) were women, the median age was 66 (IQR 58-73), 3704 (59%) had ICM, and 3778 (60%) received CRT. Of those who received CRT, 2207 (58%) patients had ICM. Overall, CRT increased the time to HFH or death (hazard ratio (HR) 0.67, 95% credible interval (CrI) 0.56-0.82, p<0.001) with no difference by etiology (HR ratio 1.06, CrI 0.87-1.29, p=0.57). CRT increased the time to death (HR 0.71, CrI 0.55-0.93, p=0.019) with no difference by etiology (HR ratio 1.06, CrI 0.80-1.43, p=0.70), although overall event rate was higher in ICM. CRT in ICM increased the median survival and time free of HFH (70 versus 50 months, p=0.0015) and had borderline effect in NICM (p=0.05) (Figure). Echocardiographic data that were available for 2430 (39%) patients showed that CRT improvements in LVEF, LVEDD, and LVESD were larger for patients with NICM.

Conclusion:
CRT increased the time to HFH or death independent of etiology of cardiac dysfunction. However, CRT led to greater increases in LVEF and reductions in ventricular dimensions for patients with NICM.
Abstract 13412: Diagnostic Performance of Machine Learning on 12-Lead Electrocardiogram for Predicting Multi-Vessel Coronary Vasospastic Angina
Authors: Shimizu Masato , Tsunoda Takahiro , Sakai Eiko , Shimizu Atsuya , Misu Yoshiki , Ryo Tateishi , Yamaguchi Masao , Nobutaka Kato , Shimada Hiroshi , Isshiki Ami , Suzuki Hidetoshi , Fujii Hiroyuki , Suzuki Makoto , Nishizaki Mitsuhiro , Sasano Tetsuo
Published: December 2023

Introduction:
Multi-vessel coronary vasospastic angina (multi-VSA) is life-threatening disease. We tried to predict multi-VSA by machine learning (ML) on 12-lead electrocardiogram (ECG).

Hypothesis:
Machine learning on 12-lead ECG has powerful diagnostic value for multi-VSA.

Methods:
We recruited 227 consecutive sinus-rhythm patients (63.6±12.9years, 136men) who underwent acetylcholine-provocation test in coronary angiography (CAG). Multi-VSA was defined as spasm in at least 2 major branches. ECG was recorded before CAG in no chest pain period. ML was performed on table data of ECG parameters using several ensemble learning methods.

Results:
79 patients (35%) showed multi-VSA, and univariate logistic regression analysis extracted 23 significant but weak predictors, the highest area under receiver operating characteristics curve (AUROC) was 0.673. Conversely, ML demonstrated high diagnostic performance (AUROC of extra trees classifier: 0.817). Shapley additive explanation method showed male, QTc, J wave in lead II, and low amplitude of Q wave in lead I/aVL played essential roles to build the ML model.

Conclusion:
Several parameters of 12-lead ECG in multi-VSA patients contains potential features of VSA, and their aggregation and ensemble learning can predict VSA with high diagnostic performance.
Abstract 13430: Cardiovascular Magnetic Resonance Imaging for Comprehensive Risk Assessment in Patients With Aortic Stenosis
Authors: Lange Torben , Beuthner Bo , Schulz Alexander , Backhaus Soeren J , Evertz Ruben , Rigorth Karl-Rudolf , Toischer Karl , Kowallick Johannes T , Hasenfuss Gerd , Puls Miriam , Schuster Andreas
Published: December 2023

Introduction:
Precise risk assessment is essential for accurate management of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). This study aimed to assess the prognostic implications of cardiovascular magnetic resonance (CMR)-derived imaging biomarkers in a large cohort of AS patients.

Methods:
145 patients with severe AS underwent CMR imaging before TAVR. Image analyses included myocardial volumes, CMR-feature-tracking derived left and right atrial (LA & RA) as well as left and right ventricular (LV & RV) strain, myocardial T1 mapping as well as late gadolinium enhancement analyses. Cardiovascular (CV) mortality was defined as primary clinical endpoint.

Results:
Patients with CV death during follow-up had significantly enlarged RV enddiastolic volumes (82.9ml/ml
2
[70.8-96.0] vs. 62.8ml/ml
2
[54.7-76.0], p<0.001) and impaired strain values of all cardiac chambers compared to patients that survived (LV GLS: -18.1% [-13.1- -20.4] vs. -22.5% [-16.1- -27.3], p=0.019; RV GLS: -22.9% [-18.6 - -25.4] vs. -27.9% [-22.9- -32.0], p=0.002; LA Es: 9.5% [7.2 - 15.4] vs. 14.3% [9.0-18.1], p=0.036; RA Es: 12.4% [6.8-14.4] vs. 16.2% [11.2-22.1], p<0.001). RA reservoir strain independently predicted CV mortality after adjusting for other CMR imaging biomarkers and clinical parameters of heart failure. Within patients with high ECV values especially RA strain further identified AS patients at high-risk for CV mortality (p=0.001 on log-rank testing).

Conclusion:
Comprehensive CMR-imaging allows accurate outcome assessment and additional identification of high-risk groups in AS patients. Especially RA strain emerged as independent predictor for cardiovascular mortality and might serve for future optimized patient management.