bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16337: Guideline-Directed Medical Therapy Use and Association With Outcomes Among Hospitalized Heart Failure With Reduced Ejection Fraction Patients During COVID-19
Authors: Srivastava Pratyaksh K , Klomhaus Alexandra , Rafique Asim , Desai Pooja S , Daniels Lori , Yancy Clyde W , Yang Eric H , Fonarow Gregg C , Parikh Rushi
Published: December 2023

Background:
The association of prior to admission guideline-directed medical therapy (GDMT) with outcomes among patients hospitalized with Heart Failure with Reduced Ejection Fraction (HFrEF) and COVID-19, as well as overall GDMT prescription patterns during the pandemic, is not well known.

Methods:
HFrEF patients (left ventricular ejection fraction ≤40%) admitted with acute decompensated heart failure (ADHF) were identified from the American Heart Association’s Get With The Guidelines Heart Failure Registry. We analyzed the association of prior to admission GDMT use with odds of in-hospital mortality, and with odds of severe COVID-19, using adjusted logistic regression models. GDMT was defined as prescription of angiotensin converting enzyme inhibitor/angiotensin II receptor blocker/angiotensin receptor-neprilysin inhibitor (ACEI/ARB/ARNI), beta blocker (BB), or mineralocorticoid receptor antagonist (MRA). We further evaluated GDMT prescription trends during the pandemic.

Results:
We identified 23,899 HFrEF patients admitted with ADHF (2/16/20-3/24/21) during the pandemic, of which 333 had a diagnosis of COVID-19. We also identified 26,459 HFrEF patients admitted with ADHF in the year prior to the pandemic (2/16/19-2/15/20). Prior to admission ACEI/ARB/ARNI, BB, or MRA use was not associated with odds of in-hospital mortality or severe COVID-19. Among all HFrEF patients, prior to admission ACEI/ARB/ARNI and BB use was lower during the pandemic compared to the year prior (Figure 1, Panel A). Prior to discharge prescription of ACEI/ARB/ARNI, MRA, and triple therapy (ACEI + BB + MRA) was higher during the pandemic compared to the year prior (Figure 1, Panel B).

Conclusion:
Among patients with HFrEF admitted with ADHF and COVID-19, prior to admission GDMT use was not associated with in-hospital mortality or severe COVID-19. GDMT prescription rates at discharge were similar to or improved during the pandemic compared with the preceding year.
Abstract 16360: Myocardial Injury and Rapid Unsupervised Topological Clustering of Electronic Health Record Features Predict Death and Length of Stay During a COVID-19 Hospitalization
Authors: Zarate Jarquin Juan C , Vazquez Eliseo T , Datta Esha , Ballal Aditya , Izu Leighton T , Haczku Angela , Whistler Jennifer L , Lopez Javier E
Published: December 2023

Background:
Elevated troponin levels, a biomarker of myocardial injury (MI), has emerged as a predictor of acute COVID-19 outcomes. However, a lack of routine use in most patients makes it difficult to evaluate as a stand-alone predictor. We aimed to combine troponin levels and a new rapid, unbiased topological clustering pipeline to test for improvements in clinical risk stratification during COVID hospitalizations.

Methods:
SlicerDicer (SD) is an intuitive, anonymous clinical electronic health record (EHR) data exploration tool that helps characterize clinical outcomes in hospital cohorts. EHR data and outcomes were extracted with SD and clustered with Mapper Plus (MP), a clustering tool that identifies clinically relevant disjoint clusters. Initial clusters were further stratified by troponin level. Measured outcomes were in-hospital mortality rates (MR) and in-hospital length of stay (LOS).

Results:
2692 patient records (2020-2021) with an overall MR of 6.3% and 97 clinical predictors were analyzed. MP identified 3 clusters with significant differences in MR (C1- 25.8%, C2- 4.2%, C3- 0.23%, P<0.001) and LOS in hours (C1- 290, C2- 132, C3- 8.3, P<0.001). Further stratification based on the troponin level reclassified the 3 MP clusters into 4 sub-clusters with distinctive MR (SC1- 32.6%, SC2- 17.3%, SC3- 2.3%, SC4-0.09%, P<0.001) based on MI presence.

Conclusions:
Using SD-based anonymous EHR data and unsupervised topological clustering with MP during a COVID hospitalization provides a low-effort, robust pipeline that predicts in-hospital MR and LOS. When MP clusters were re-stratified by the presence of MI, new sub-clusters (4) showed reclassification of both high- and low-risk patients. This risk classification schema provides a new pragmatic and computational framework for selecting hospitalized patients with COVID that can benefit from further in-hospital therapies and mechanistic studies on the role of myocardial injury in COVID-19 prognosis.
Abstract 16364: Presence of Ramus Intermedius Artery is Associated With Higher Atherosclerotic Plaque Burden in the Left Main Stem in Coronary CT Angiography
Authors: Pourafkari Leili , Kinninger April , Fazlalizadeh Hooman , Manubolu Venkat Sanjay , Roy Sion , Budoff Matthew J
Published: December 2023

Introduction:
Ramus intermedius (RI) is a variant vessel arising from left main (LM) bifurcation that supplies the lateral wall. It is thought that presence of RI would result in increased coronary turbulence in LM which in return could affect atherosclerotic plaque formation process. We aimed to investigate the association of presence of RI with presence of atherosclerotic plaque and stenosis in left main (LM).

Hypothesis:
Presence of RI artery associates with higher frequency of atherosclerotic plaque formation in LM

Methods:
We performed a large retrospective single-center study, including consecutive subjects who completed a CTA exam from October 2006 to December 2022 in Los Angeles, California to determine if presence of RI associated with higher LM coronary plaque burden. Chi-Square test was used to examine level of left main plaque burden and percent stenosis in subjects where the Ramus is present versus absent.

Results:
Among the 11,497 subjects, the average age was 62.0±12.4 years, 64% male, and 11% had the Ramus segment present. Those with a Ramus segment present were more likely to have mild, moderate or severe plaque burden (41% versus 26%, p=<0.0001) in their left main. (Table 1). Additionally, subjects with RI has higher prevalence of any degree of LM stenosis compared to those without RI (P-Value<0.0001).

Conclusions:
Our results suggest that the presence of RI is associated with higher prevalence of atherosclerotic plaques and higher degree of stenosis in LM stem.
Abstract 16368: Opioid Withdrawal-Induced Takotsubo Cardiomyopathy in Hypertrophic Cardiomyopathy
Authors: O'Gorman Brendan P , Pathangey Girish , Moudgal Rohitha A , Shah Kajal P , WELCH Terrence D
Published: December 2023

Introduction:
This case highlights opioid withdrawal-induced Takotsubo cardiomyopathy (TCM) in a patient with pre-existing hypertrophic cardiomyopathy (HCM) and discusses the concurrent management.

Clinical Presentation:
An 85-year-old female with HCM, depression, and chronic back pain presented with generalized weakness five days after opioid discontinuation. She exhibited elevated troponin levels and ST elevation in anteroseptal leads, concerning for STEMI. Coronary angiogram revealed nonobstructive coronary artery disease. Transthoracic echocardiogram revealed newly reduced EF 45%, hyperdynamic basal left ventricle, and akinetic mid-distal left ventricle, consistent with TCM. Notably, marked basal anteroseptum thickness and systolic anterior mitral valve motion with left ventricular outflow tract obstruction (LVOTO) and a peak gradient of 92 mmHg. Presentation was complicated by hypotension, pulmonary edema and cardiorenal syndrome. β-blocker use initially deferred, opting for phenylephrine and diuresis until stabilization permitted β-blocker introduction.

Discussion:
We present a unique case of TCM precipitated by opioid withdrawal in a patient with existing HCM. Standard critical care management for TCM involves hemodynamic support until cardiac function recovers, though the use of vasopressors and inotropes remains controversial. Importantly, this case demonstrates severe provoked LVOTO, mimicking acute myocardial ischemia. Recognizing such scenarios is vital, as inappropriate use of vasodilators or inotropes can be fatal. Class I-IIa recommendations endorse β-blockers and vasoconstrictors for severe provoked LVOTO with hypotension and pulmonary edema. Phenylephrine, a selective α-agonist, maintains LVOT turgidity through preload enhancement, while β-blockers facilitate ventricular filling and reduce LVOT pressure gradient. Further research is warranted as current evidence level remains class C.
Abstract 16372: Prognostic Value of Baseline Right Ventricular Dysfunction Using TAPSE and TAPSE to PASP Ratio in Patients Undergoing Mitra-Clip: Systematic Review and Meta-Analysis
Authors: Abu Rmilah Anan , Ghaly Ramy , Pfeiffer Carlos , Camba Victor , HAG SAEED MOHAMED , Khojah Abdulrahman , Chib Anjula , Tabash Aziz , Raper John , Jaber Suhaib , Volansky Paul , jagtap mandar
Published: December 2023

Introduction:
Transcatheter edge-to-edge mitral valve repair (TEER) using Mitra-clip is an established therapy for high-risk surgical candidates who are refractory to optimal medical treatment. Several reports have shown that right ventricular dysfunction (RVD) is associated with increased morbidity and mortality in heart failure (HF) patients. Emerging data on the relationship between baseline RVD and post-TEER mortality has been published.

Objective:
Our main goal is to assess the prognostic impact of baseline RV function markers; tricuspid annular plane excursion (TAPSE) and TAPSE/PASP (pulmonary arterial systolic pressure) ratio, as an expression of the right ventricle-pulmonary artery coupling following Mitra-Clip.

Methods:
MEDLINE and EMBASE were searched for studies discussing outcomes of Mitra-Clip in patients with and without RV dysfunction as expressed by TAPSE or TAPSE:PASP ratio. Two reviewers independently screened the studies and extracted the pertinent survival data. Odds ratios (OR) with 95% confidence interval were calculated using a random-effects model.

Results:
Twelve reports enrolling 3515 patients (1443 with and 2072 without pre-existing RVD) were included. Patients with RVD had OS reduction after Mitra-Clip by 55% at 6 months, 60% at one year, and 63% at two years [OR: 0.45 (0.35-0.58), 0.40 (0.33-0.48), 0.37 (0.31-0.45) respectively;
P
< .001] compared to normal RV group. Likewise, HR readmission free survival was minimized among RVD patients by 53% at 6 months, 56% at one year, and 59% at two years compared to normal RV group [OR: 0.47 (0.35-0.65), 0.44 (0.35-0.55), 0.41 (0.30-0.56) respectively;
P
< .00001]. TAPSE:PASP ≤ 0.30-0.37 was associated with lower OS and HF re-admission free survival at 6 months (OR: 0.37, 0.44;
P
< .00001) and 1 year (OR: 0.35, 0.41;
P
< .00001) after Mitra-Clip. Furthermore, TAPSE ≤ 15-16 negatively impacted the OS at 6 months (OR: 0.40
P
< .00001) and 1 year (OR: 0.50;
P
< .00001) after Mitra-Clip.

Conclusions:
Pre-existing RV dysfunction as expressed by TAPSE ≤15-16 or TAPSE:PASP ratio ≤ 0.30-0.37 decreased the overall survival and HF readmission free survival after Mitra-Clip therapy. Further research is warranted to guide interventional timing based on the degree of RV dysfunction.
Abstract 16393: Incident Cardiometabolic Risk Factors in Breast Cancer Patients Stratified by Race and Ethnicity
Authors: Diaz Andrea E , Kwan Marilyn L , Laurent Cecile A , Roh Janise M , Iribarren Carlos , Rana Jamal S , Kushi Lawrence H , Reding Kerryn , Rillamas-Sun Eileen , Quesenberry Charles P , Greenlee Heather , Cheng Richard K
Published: December 2023

Background:
The development of incident cardiometabolic risk factors in racial and ethnic minority groups of women with breast cancer (BC) has not been well-characterized.

Hypothesis:
We expect a higher risk of incident cardiometabolic risk factors [hypertension (HTN), diabetes (DM), dyslipidemia] in racial and ethnic minority women with BC without a history of these conditions compared with non-Hispanic White (NHW) women with BC.

Methods:
The Pathways Heart Study is a prospective cohort study of women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California. Cumulative incidence rates of incident HTN, DM, and dyslipidemia determined from the electronic health record (using two separate ICD 9/10 codes in the 2 years prior to BC diagnosis, lab values, and medication dispensings) were calculated using a competing risk framework for overall death. Sub-distribution hazard ratios for incident HTN, DM, and dyslipidemia were estimated using Fine and Gray proportional hazards regression, adjusted for
a priori
identified covariables, and stratified by race and ethnicity.

Results:
A total of 14,942 women with BC had mean age 61.2 years and were 65% NHW, 7.5% Black, 14.4% Asian, 11.9% Hispanic, 0.4% Pacific Islander, and 0.8% American Indian/Alaska Native. Compared to NHW women, Black, Hispanic, Asian, and Pacific Islander women had higher risk of incident DM (Table 1). Black and Asian women had higher risk of incident HTN compared with NHW women. Asian women had higher risk of incident dyslipidemia compared with NHW women.

Conclusions:
Racially and/or ethnically diverse women with BC experienced higher risk of incident DM, HTN, and dyslipidemia compared with NHW women with BC. Asian women consistently had a higher risk of each cardiometabolic risk factor. It is critical to better characterize health disparities in the field of cardio-oncology to inform future cardiovascular disease prevention and treatment strategies.
Abstract 16398: Impact of Low-Dose Rivaroxaban Plus Aspirin on Total Vascular Events in Fragile Patients With Peripheral Artery Disease: Insights From VOYAGER PAD
Authors: Canonico Mario Enrico , Low Wang Cecilia C , Debus Sebastian , Nehler Mark , Patel Manesh R , Anand Sonia S , Capell Warren , Muehlhofer Eva , Haskell Lloyd P , Berkowitz Scott D , Bauersachs Rupert , Bonaca Marc P
Published: December 2023

Background:
Rivaroxaban 2.5 mg BID reduced major adverse limb events (MALE) and total vascular events in patients with symptomatic peripheral artery disease (PAD) after lower extremity revascularization (LER) in VOYAGER PAD. The safety and efficacy of rivaroxaban on MALE and total vascular events in fragile patients with PAD has not been described.

Hypothesis and Methods:
Patients were categorized as fragile based on prespecified criteria (age > 75 years or weight ≤ 50 kg or baseline eGFR < 50 mL/min). MALE was defined as composite of acute limb ischemia (ALI) and major amputation. Total vascular events include cardiovascular, MALE, peripheral revascularizations and venous thromboembolism events. Same-day vascular events are consolidated into a single event. The main safety outcome was TIMI major bleeding.

Results:
A total of 1,669 (25%) subjects of 6,564 randomized were categorized as fragile at baseline. Rivaroxaban reduced the risk of MALE particularly in fragile (HR 0.56; 95% CI 0.38 - 0.81) vs non-fragile patients (HR 0.82; 95% CI 0.67 - 1.00, p-interaction 0.07, figure upper panel) with the benefits in fragile patients driven by reduced ALI (HR 0.47; 95% CI 0.30 - 0.75). Rivaroxaban reduced the occurrence of total vascular events at 3 years in fragile patients with absolute rates of 82.1 events/100 patients on rivaroxaban vs 99.3 events/100 patients on placebo (HR 0.81; 95% CI 0.68 - 0.98). Similar benefit was seen in non-fragile patients 70.4 events/100 patients on rivaroxaban vs 81.6 events/100 patients on placebo, HR 0.90; 95% CI 0.81-1.00 (figure, lower panel). Rivaroxaban increased TIMI major bleeding similarly in fragile (HR 1.66; 95% CI 0.87 - 3.19) and non-fragile (HR 1.37; 95% CI 0.83 - 2.24, p-interaction 0.65).

Conclusions:
In a high-risk PAD population rivaroxaban reduces MALE and total vascular events and increases bleeding regardless of fragile status. These data may assist in personalization of antithrombotic therapy in this high-risk population.
Abstract 16420: Coronary Crown Length and Volume Assessed With Coronary CT Angiography Improves the Diagnosis of Ischemia
Authors: Malkasian Shant , Nurmohamed Nick , Marques Hugo , Hubbard Logan , Molloi Sabee , Min James K , Earls James
Published: December 2023

Background:
Coronary artery tree length and lumen volume follow an allometric power-scaling relationship via

Length = K
LV
* Volume
0.78

. Derangement from this morphometric relationship may indicate atherosclerosis.

Methods:
This study was a retrospective analysis of the CREDENCE trial, a large multicenter international study. In CREDENCE, patients with suspected CAD underwent CCTA followed by invasive coronary angiography and fractional flow reserve (FFR). For this study, 315 patients with invasive FFR measurements were selected. There were 945 vessel territories, with 681 nonischemic territories (FFR > 0.80) and 264 ischemic territories (FFR ≤ 0.80). Following AI-enabled quantitative CT analysis (AI-QCT) (Cleerly; Denver, CO), coronary territories were split into “stem-crown” units, every 1 cm along each territory. Territories were truncated at 1.5 mm lumen diameter. A single parameter allometric scaling model was employed using a previously validated exponential term (L
CROWN
= K
LV
* V
CROWN
0.78
). After log-transformation, K
LV
was determined via fitting with generalized estimating equations.

Results:
The mean K
LV
for ischemic and nonischemic territories was 28.92±4.77 and 25.02±4.84 (p <0.001). The ROCAUC for K
LV
, diameter stenosis (DS
AI-QCT
), and total plaque volume was 0.72 [0.69, 0.76], 0.85 [0.83, 0.88], and 0.70 [0.66, 0.73], respectively, for the diagnosis of ischemia (K
LV
vs. diameter stenosis: p-value <0.001; K
LV
vs. total plaque volume: p-value=0.400; DS
AI-QCT
vs. total plaque volume: p-value <0.001). Multivariable ROCAUC analysis of K
LV
and diameter stenosis (model 2), and K
LV
, diameter stenosis, and total plaque volume (model 3) was 0.87 [0.85, 0.90], 0.87 [0.85, 0.90], respectively.

Conclusion:
Ischemic coronary territories demonstrated significantly larger K
LV
than nonischemic territories. Moreover, using K
LV
and DS
AI-QCT
provided incremental improvement in the diagnosis of ischemia.
Abstract 16425: Incidence of New-Onset Hypertensive Disorders of Pregnancy Before and During the Early COVID-19 Pandemic in the United States, 2018-2021
Authors: Everitt Ian K , Peesay Tejasvi , Huang Xiaoning , Cameron Natalie , Grobman William , Khan Sadiya S
Published: December 2023

Introduction:
The incidence of new-onset hypertensive disorders of pregnancy (HDP) has increased in recent years. During the COVID-19 pandemic, blood pressure control worsened in non-pregnant populations. Therefore, we sought to examine whether the incidence of HDP changed with the onset of the COVID-19 pandemic.

Methods:
A serial cross-sectional study of nulliparous individuals aged 15-44 years with singleton live births was conducted using the National Center for Health Statistics Natality Data Files from 2018-2021. HDP was determined by the professional attendant at birth. Maternal social determinants of health (SDoH), including education level, Medicaid insurance, and rurality of residence, were self-reported. Interrupted time series analyses compared the monthly national incidence of HDP before (1/2018-2/2020) and during (5/2020-12/2021) the COVID-19 pandemic, overall and stratified by maternal SDoH, adjusting for seasonal autocorrelation.

Results:
The sample included 5,246,061 pregnant individuals (22.2% Hispanic, 7.4% non-Hispanic Asian, 13.3% non-Hispanic Black, 53.8% non-Hispanic White). The incidence of HDP was 9.22% in 1/2018 and 12.15% in 12/2021. The incidence of HDP increased before (0.07±0.01%/month) and during the pandemic (0.06±0.01%/month), with no acceleration after pandemic onset (p=0.66,
Figure
). There was no significant difference in monthly trends when stratified by maternal SDoH groups.

Conclusions:
Nearly 1 in 8 individuals in 2021 had a pregnancy complicated by new-onset HDP in the US. While the early COVID-19 pandemic was not associated with a significant acceleration, the incidence of HDP continues to steadily increase.
Abstract 16427: Despite Machine Learning Models, QRS Duration Remains the Superior ECG Criterion for Predicting Left Ventricular Dilation in Patients With Left Bundle Branch Block
Authors: DeBauge Ashley , Harvey Christopher , Fairbank Tyan , Ranka Sagar , Jiwani Sania , Sheldon Seth , Reddy Madhu , Noheria Amit
Published: December 2023

Introduction:
The utility of ECG to diagnose left ventricular (LV) dilation in patients with left bundle branch block (LBBB) is not known. We sought to compare the diagnostic yield of ECG using (i) QRS duration, (ii) published LVH criteria, and (iii) machine learning (ML) models to detect increased left ventricular end diastolic volume indexed (LVEDVi) in the setting of LBBB.

Hypothesis:
ML is superior to QRS duration and LVH criteria to detect increased LVEDVi among LBBB.

Methods:
12-lead ECGs were processed to reconstruct orthogonal X, Y, Z leads using Kors’s matrix and obtain root-mean-squared (3D) ECG. R wave, S wave and overall amplitudes, voltage-time-integrals (VTIs), and other ECG features were extracted from all ECG leads. ML algorithms [logistic regression (LR), support vector classifier (SVC), decision trees (DT), random forest (RF), gradient boosted machine (GBM) and boosted trees (BT)] were trained to predict increased LVEDVi (women >61 mL/m
2
, men >74 mL/m
2
) from ECG features on a training set of 2668 ECGs with typical LBBB and echocardiogram within 45 days before or after ECG. LVEDV was measured using ASE biplane method of discs. We obtained ROC AUCs for prediction of increased LVEDVi by (i) QRS duration, (ii) published LVH criteria, and (iii) ML models in a separate validation set of adults with typical LBBB.

Results:
Among the validation set of 413 adults (53% women, age 73±12 yr) with LBBB, QRS duration alone had a higher AUC (women 0.668, men 0.699) for diagnosing increased LVMi compared to standard LVH criteria (Table). The best ML model (RF with overall AUC 0.694) did not substantially outperform QRS duration alone.

Conclusions:
In patients with LBBB, QRS duration ≥150 in women and ≥160 in men is a superior predictor of LV dilation than traditional ECG-based LVH criteria, with no additional value added by ML methods.
Abstract 16428: Impact of Low-Dose Rivaroxaban Plus Aspirin on Myocardial Infarction in Patients With Peripheral Artery Disease With and Without Concomitant Coronary Artery Disease: Insights From VOYAGER PAD
Authors: Canonico Mario Enrico , Morrison Justin , Anand Sonia S , Patel Manesh R , Debus Sebastian , Nehler Mark , Hess Connie N , Hsia Judith A , Capell Warren , Muehlhofer Eva , Haskell Lloyd P , Berkowitz Scott D , Bauersachs Rupert , Bonaca Marc P
Published: December 2023

Background:
Patients with peripheral artery disease (PAD) are at heightened risk of major adverse cardiovascular events (MACE). In VOYAGER PAD, rivaroxaban 2.5 mg BID reduced ischemic risk in PAD patients after lower extremity revascularization (LER). Whether the benefits for MACE and in particular for Myocardial Infarction (MI) differ in those with and without clinically known coronary artery disease (CAD) has not been described.

Hypothesis and Methods:
VOYAGER PAD randomized patients with symptomatic PAD undergoing LER to rivaroxaban 2.5 mg BID plus aspirin versus aspirin alone. MACE was defined as composite of MI, ischemic stroke, or cardiovascular death. Subtypes of MI were adjudicated according to the Universal Definition. Comorbid CAD was a prespecified subgroup.

Results:
Of 6,564 symptomatic PAD randomized, 2,083 (32%) had documented CAD at baseline. The benefit of rivaroxaban plus aspirin was greater for MACE in those with vs without CAD (HR 0.79, 95% CI 0.62 - 1.00 vs HR 1.12, 95% CI 0.92 - 1.36; p-interaction 0.03). Similarly, MI reduction with rivaroxaban plus aspirin was greater for those with vs without CAD (HR 0.78, 95% CI 0.56 - 1.10 vs HR 0.96, 95% CI 0.69 - 1.34; p-interaction 0.39). Considering MI subtypes, the effect of rivaroxaban plus aspirin on type 1 MI was consistent in patients with CAD (HR 0.91, 95% CI 0.58 - 1.42) and without CAD (HR 0.74, 95% CI 0.74 - 1.11, p-interaction 0.50). However, a trend towards benefit of rivaroxaban plus aspirin was seen for Type 2 MI in those with CAD (HR 0.71, 95% CI 0.41 - 1.24) but not in patients without CAD (HR 1.66, 95% CI 0.89 - 3.09, p-interaction 0.0475, figure). Type 4 MI was infrequent regardless of CAD.

Conclusions:
Rivaroxaban plus aspirin had consistent effects in MACE for PAD and CAD patients undergoing LER. Our analysis of MI subtype suggests that events adjudicated as MI due to supply demand mismatch (Type 2) may have a thrombotic component and are lowered with rivaroxaban and aspirin in PAD and CAD patients undergoing LER.
Abstract 16457: Characterization of LTBP2 Mutation in Causing Mitral Valve Prolapse
Authors: shpitzen Shoshi , Rosen Haim , Ben-Zvi Ayal , Meir Karen , Levin Galina , Gutgold Amichay , Ben-Dor Shifra , haffner rebecca , Zwas Donna , Leibowitz David , Levine Robert A , Gilon Dan , Leitersdorf Eran , Tessler Idit , Reshef Noga , Durst Ronen
Published: December 2023

Introduction:
Mitral Valve Prolapse (MVP) is a cardiac valvular disorder often associated with significant morbidity and mortality with a prevalence of 2.4% in the general population. Familial studies of MVP suggest an autosomal dominant model of inheritance with incomplete penetrance.

Hypothesis:
The aim of the current study was to identify a genetic etiology for MVP through trait segregation in a progeny with MVP.

Methods:
We used exome sequencing and segregation analysis to identify mutations linked to MVP in a progeny which includes members. We then generated two strains of mice using Crisper-Cas9 technology, a complete knockout and a knock-in mouse of the top candidate mutation. At 6 months of age echocardiography was done, the mice were sacrificed and the valves were examined pathologically as well as histologically by Movat pentachrome staining. The readers of both the echo and histology were blinded to the genotype.

Results:
Of 11 genes with rare deleterious mutations only LTBP2 Val1506Met variant (minor allele frequency of 0.0001) segregated with the trait with a LOD score of 1.5[-DR1] . Knockout mice were more likely to demonstrate myxomatous changes by histology (7 of 9 vs 2 of 6 animals, p=0.03) and echocardiography (14 of 22 vs 1 of 8, p=0.01). Knock-in mice demonstrated significantly higher phenotype rate by histology (8 of 8 vs 0 of 7, p<0.0005) and higher nominal phenotype by echo (4 of10 vs 1 of 9, p=0.2).

Conclusions:
LTBP2 Val1506Met variant segregated with MVP in a large pedigree. Animal models that recapitulate the phenotype suggest that the mutation is indeed pathogenic and leads to myxomatous valvular change.
Abstract 16462: Phenotypic Features of Lipidic Plaque in Patients With Polyvascular Disease: Findings From the Reassure Near-Infrared Spectroscopy Imaging Multi-Center Registry
Authors: Katasako Aya , Kataoka Yu , Funabashi Sayaka , Iwai Takamasa , Sawada Kenichiro , Matama Hideo , Miura Hiroyuki , Honda Satoshi , Yoneda Shuichi , Takagi Kensuke , Otsuka Fumiyuki , Takamisawa Itaru , Kensaku Nishihira , Asaumi Yasuhide , Tsujita Kenichi , Noguchi Teruo
Published: December 2023

Introduction:
Polyvascular disease (PolyVD) is a high-risk atherosclerotic phenotype presenting worse cardiovascular outcomes. However, its atherosclerotic features remain to be fully elucidated yet. Near-infrared spectroscopy (NIRS) imaging quantifies lipidic plaque associated with clinical outcome.

Hypothesis:
Given a clustering of atherogenic risks in PolyVD, PolyVD may exhibit a distinct plaque phenotype, which accounts for their outcome.

Methods:
224 culprit lesions in 203 CAD patients receiving PCI were evaluated by NIRS imaging. PolyVD was defined as those with additional ASCVD (stroke and/or LEAD). NIRS-derived lipidic plaque feature (maxLCBI
4mm
) and clinical outcome (all-cause death+non-fatal MI+stroke) were compared in PolyVD and non-PolyVD subjects.

Results:
28.6% of study subjects exhibited PolyVD. They were older (77 v. 71 years, p=0.02) with a greater frequency of CKD (61 v. 45%, p=0.03). Under the use of statin (81 v. 71%, p=0.15) and ezetimibe (32 v. 21%, p=0.09), PolyVD patients had a lower LDL-C level (73 v. 84 mg/dL, p=0.01). Despite their LDL-C control, maxLCBI
4mm
did not differ in two groups (median: 458 v. 576, p=0.19). Moreover, 64% of PolyVD patients still showed maxLCBI
4mm
≧400 (69% in non-PolyVD, p=0.44). On multivariate analysis, ACS independently predicted maxLCBI
4mm
≧400 (Figure) in PolyVD patients. Of note, PolyVD presenting ACS had a higher maxLCBI
4mm
(790 v. 411, p=0.001) compared to those without ACS, whereas this relationship did not exist in non-PolyVD (622 v. 561, p=0.19, Figure). During the 3-year observational period, PolyVD was associated with an elevated risk of MACE (p=0.002).

Conclusions:
Despite lowering LDL-C levels, PolyVD harbored a large amount of lipidic materials, accompanied by worse cardiovascular outcomes. Given the relationship of ACS with maxLCBI
4mm
in PolyVD, additional therapies which modulates ACS-related inflammatory activity may be warranted to alter their disease substrate and outcomes.
Abstract 16473: Validation of the Artificial Intelligence-Based 5-Lead 3D Vectorcardiography in Comparison to the 12-Lead ECG in a Mixed Population
Authors: Schmidt-Lucke Caroline , Lischke Betty , Weber Eugenia , Günther Daniel , Schomoeller Anne , Schmidt-Lucke André
Published: December 2023

Introduction:
Artificial Intelligence-based 5-lead 3D-vectorcardiography (5L3DVCG-AI) offers additional information over 12-lead electrocardiography (ECG) in the detection of significant coronary stenoses. 5L3DVCG-AI is under investigation as a new screening tool for coronary vascular disease (CVD). Hypothesis: We tested the hypothesis of variables from the reconstructed “12-lead ECG” (5L12L-ECG, modified Dower transformation) corresponding with the standard 12-lead ECG (ECG).

Methods:
In this monocentric exploratory retrospective study, raw data of 331 patients with 5L3DVCG-AI and ECG were included. Cardiac pathology (CP) was categorised as exclusion of any CP (control), mild CP or overt CP by 2 independent cardiologists. The following variables were compared: RR-interval, P, PQ, QRS, QT, QTcB, QTcF, QRS-morphology, and ST-morphology. Cardiovascular risk factors (CVRF) were quantified with the modified PROCAM score.

Results:
From 331 patients (m:w 60:40%, 50.0 ± 19.8 years) of mixed ethnicity and moderate CVRF (2.1 ± 1.2), 70% were controls, 21% had mild CP and 9% overt CP. All variables from reconstructed 5L12L-ECG correlated to the corresponding individual variables from ECG (r= 0.49 to 0.7, p<0.001). With identical RR-intervals in both methods, all defined variables were significantly, but irrelevantly or mildly (Cohen’s d) different in 5L12L-ECG compared to ECG (P 106 ± 12 vs. 109 ±20 (
d
=0.3), PQ 152 ± 24 vs. 159 ± 26 (
d
=0.3), QRS 105 ± 16 vs. 97 ± 14 (
d
=0.7), QT 380 ± 33 vs. 396 ± 27 (
d
=0.46), QTcB 432 ± 31 vs. 426 ± 25 (
d
=0.57), QTcF 414 ± 26 vs. 416 ± 19 (
d
=0.53). 5L3DVCG-AI was able to distinguish between controls and patients with CVD (Sensitivity 78%, Specificity 66%, p=0.01). Comparing heart axis, there was a small, but significant difference with a significant correlation between methods (r=0.30, p<0.01).

Conclusions:
The easy to use 5-lead ECG may thus be used in clinical practice to reconstruct valid 12-lead ECG curves without major training or expertise. Additionally, 5L3DVCG-AI can identify persons at risk for CVD. Shorter values for the defined variable will have to be considered when interpreting 5L12L-ECG and separate “normal” value ranges will be given and validated in the ongoing prospective large-scale performance clinical trials.
Abstract 16478: Effect of Sodium Glucose Cotransporter 2 Inhibitors on Major Adverse Cardiovascular Events in Cancer Patients Treated With Immune Checkpoint Inhibitors
Authors: Huang Pin-Chia , Neilan Tomas G , Heemelaar Julius , Ma Kevin Sheng-Kai
Published: December 2023

Introduction:
The cardiac adverse events (irAEs) secondary to immune checkpoint inhibitors (ICI) are associated with a high rate of morbidity and mortality. There are no data on the effect of concomitant sodium glucose cotransporter 2 inhibitors (SGLT2i) on the rates of major adverse cardiovascular events (MACE) among patients treated with an ICI.

Hypothesis:
Whether, the use of SGLT2i among ICI-treated patients may reduce MACE.

Methods:
This was a population-based cohort study between 2014 and 2023 including cancer patients treated with ICI aged over 18 years across the United States. SGLT2i use while on an ICI was defined as the initiation of SGLT2i therapy after the first record of ICI treatment among patients currently undergoing ICI therapy. The risk of incident MACE in patients on an ICI who were also prescribed an SGLT2i therapy was compared with 1:1 propensity score-matched patients on ICI who were never prescribed an SGLT2i. Hazard ratios (HRs) and 95% confidence intervals (CIs) for MACE were estimated using Cox proportional hazards regression. MACE was defined as a composite of myocardial infarction, heart failure (HF), and ischemic stroke.

Results:
There were 216 cancer patients undergoing ICI therapy who were newly treated with SGLT2i. These were compared to 216 controls. Over a mean follow-up period of six years, there were 107 MACE events. There were 44 events (20.4%) among those on an SGLT2i and 63 among controls (HR=0.61, 95% CI: 0.41-0.90; log-rank test p=0.011). Of the individual components of MACE, rates of HF were lower where there were 22 HF events (20.4%) among those on an SGLT2i and 37 among controls (HR=0.51, 95% CI: 0.30-0.86; log-rank test p=0.010). There were no differences in the rates of stroke (HR: 0.55, 95% CI: 0.29-1.04) and myocardial infarction (HR: 0.97, 95% CI: 0.38-2.43).

Conclusions:
In an observational, retrospective study, SGLT2i therapy was associated with a reduced risk for cardiac events compared to those who never treated with SGLT2i. These findings underscore the potential therapeutic value of SGLT2i in the prevention of MACE in cancer patients receiving immunotherapy and warrant further research.
Abstract 16482: Proteomic Measures Associated With Leisure-Time Physical Activity and Heart Failure Risk in Late-Life - The Atherosclerosis Risk in Communities Study
Authors: Hegde Sheila , Yang Yimin , Lamberson Victoria , Claggett Brian , Skali Hicham , Evenson Kelly R , Steffen Brian T , Coresh Joseph , Ndumele Chiadi E , Yu Bing , Shah Amil M
Published: December 2023

Introduction:
Leisure-time physical activity (LTPA) is associated with lower heart failure (HF) risk. However, the underlying molecular mechanisms by which LTPA impacts HF risk is unclear.

Methods:
We evaluated participants at Atherosclerosis Risk in Communities study visits 3 (1993-95) and 5 (2011-13) with plasma proteomics data (Somascan v4) and without HF or stroke. LTPA was assessed by the Baecke questionnaire as metabolic equivalent (MET)-minutes/week. We performed cross-sectional associations of 4,955 proteins with LTPA at visit 3 and then at visit 5 LTPA using multivariable quantile regression models at Bonferroni-corrected significance (p<1e-5, p<0.0004, respectively). We related these proteins to incident HF after visit 3 and then visit 5 using multivariable Cox regression models at Bonferroni-corrected significance (p<0.00086, p<0.003, respectively).

Results:
Thirty-nine proteins were associated with LTPA at visit 3 (n=10,402; age 60±6 yrs, 54% women; mean 688.6 MET-minutes/week, 773 incident HF events) and visit 5 (n=4,135; 75±5 yrs, 58% women; mean 834.8 MET-minutes/week, 362 events), of which 5 proteins were also associated with incident HF at both visits. Higher levels of THBS2, GABARAP, and BAGE2 were associated with lower LTPA and higher HF risk while higher levels of ART3 associated with higher LTPA and lower risk of incident HF (Figure). PTK7 demonstrated discordant associations with LTPA and HF risk. Levels of THBS2, GABARAP, BAGE2, and ART3 accounted for a significant proportion of the LTPA-HF association (p<0.05).

Conclusion:
Large-scale proteomics can identify novel biomarkers potentially linking LTPA to HF risk. Further study is needed of THBS2, GABARAP, BAGE2, and ART3, which may link the association of LTPA on HF.
Abstract 16491: The Relationship Between Cardiovascular Health and 10-year Atherosclerotic Cardiovascular Risk in American Adults
Authors: Grandhi Gowtham R , Alebna Pamela L , Armendano Joaquin Ignacio , Tasdighi Erfan , Osei Albert D , Blaha Michael J , Mehta Anurag
Published: December 2023

Introduction:
Life’s Essential 8 (LE8) is a metric of overall cardiovascular health (CVH) while 10-year atherosclerotic cardiovascular disease (ASCVD) risk is routinely used to guide primary prevention. Yet, the relationship between LE8 and 10-year ASCVD risk is unclear.

Hypothesis:
CVH has an inverse relationship with 10-year ASCVD risk in adults aged 40–75 years from the National Health and Nutrition Examination Survey 2017-2020 cycle.

Methods:
Adults with ASCVD and data missing to calculate 10-year ASCVD risk and LE8 scores were excluded. LE8 score was estimated from the mean of LE8 components (scored 0 to 100), with scores ≥80, 79–50, and <49 grouped into ideal, intermediate, and poor CVH, respectively. 10-year ASCVD risk was estimated using pooled cohort equation, with scores <5%, 5–19.9%, and ≥20% grouped as low, borderline/intermediate, and high risk, respectively. The survey weighted chi-square and ANOVA analysis was performed.

Results:
We included 1,550 adults representing nearly 45 million US adults with a mean age of 57.8 years, 35.3% women. Overall, 35.4%, 42.3%, and 22.3% had low, borderline/intermediate, and high 10-year ASCVD risk, respectively. Low, borderline/intermediate, and high-risk individuals had a mean LE8 score of 68.2, 61.8, and 62.6 (p-value: <0.001) while 18.1%, 7.4%, and 5.6% (p-value: 0.002) had ideal CVH, respectively. Diet, nicotine exposure, body mass index (BMI), and blood lipids metrics were very low across the risk groups (figure). Additionally, the mean blood pressure metric was 41.3 among high-risk and 61.1 among intermediate/borderline-risk individuals.

Conclusions:
The prevalence of ideal CVH is very low across all 10-year ASCVD risk groups primarily due to poor diet, nicotine exposure, high BMI, and high blood lipids. Since ASCVD risk is predominantly age-dependent and given comparable LE8 scores among borderline/intermediate and high-risk individuals, LE8 may denote an age-independent long-term/lifetime risk.
Abstract 16532: Mosaic Loss of Y Chromosome in Leukocytes Predicts Death in Patients With Chronic Heart Failure Across the Whole Spectrum of Ejection Fraction
Authors: Cremer Sebastian , Kirschbaum Klara , Tombor Lukas , Mas-Peiro Silvia , Rasper Tina , Leistner David M , Dimmeler Stefanie , Zeiher Andreas M
Published: December 2023

Aims:
Mosaic loss of Y chromosome (LOY) in men increases with age and correlates with clonal expansion of myeloid cells. Experimental modeling demonstrated that LOY in hematopoietic cells leads to diffuse cardiac fibrosis and subsequent development of heart failure in mice. Cardiac fibrosis is an important pathogenic feature in heart failure irrespective of etiology. Therefore, we investigated the prognostic significance of LOY in men with chronic heart failure.

Methods and Results:
In a total of 705 male patients with chronic heart failure with reduced and preserved ejection fraction, LOY was determined by digital PCR of peripheral blood cells by assessing the 6bp sequence difference between the AMELX and AMELY genes. ROC analysis relating the extent of LOY to mortality revealed a LOY of 17% as the optimal cut-off value to predict death during follow-up. LOY >17% was observed in 18.6% of all patients, increased with age and was associated with increased mortality after three years (13,7% in patients without LOY compared to 29.0% in patients with LOY, p<0.001, Figure 1). LOY remained an independent predictor of death in multivariate analysis including, age, LVEF and nt-pro BNP serum levels (HR 1,67; 95% CI 1.08-2.57; p=0.017). Importantly, LOY was associated with increased mortality in patients with heart failure with reduced ejection fraction defined as LVEF < 50% (p<0.001) as well as in patients with preserved LVEF ≥ 50% (p=0.01).

Conclusion:
Among patients with heart failure, LOY in blood cells is associated with increased risk of death across the complete range of ejection fraction. Further studies are warranted to discern if LOY associates with cardiac fibrosis in men with heart failure and triggers increased profibrotic signaling. The results of this study may inform trials evaluating precision-targeted anti-fibrotic therapies in patients with chronic heart failure.
Abstract 16544: A Multicenter Validation of a Noninvasive Brachial Cuff-ECG System for Estimation of Elevated Left Ventricular End Diastolic Pressure
Authors: Shavelle David , Rinderknecht Derek , Jin Weiwei , Chiu W. Brian , Krupa Asia , Pahlevan Niema M , Cook Kendra , Mendelsohn Farrell , Cawthon Thomas , Reeves Ryan , mcnamara richard , Madder Ryan D , Nguyen Hoang , Elsayed Sarah , Bahadorani John , Lamont Daniel , Yang Tae Y , Bailey Steven R
Published: December 2023

Introduction:
Measurement of left ventricular end diastolic pressure (LVEDP) is an established diagnostic method to evaluate all types of heart failure (HF). Invasive measurement of LVEDP requires an in-hospital procedure which limits accessibility. A noninvasive technique for detecting elevated LVEDP would significantly improve the diagnosis of HF, particularly in the outpatient setting. Herein we present the results of a multicenter study to validate a noninvasive system to detect elevated LVEDP.

Methods:
The Vivio System includes a modified blood pressure cuff and single lead ECG to capture brachial artery waveforms to assess preload, afterload and contractility. A model was created to identify patients with elevated LVEDP (> 18mmHg). 728 patients were enrolled from 7 medical centers in the USA. All patients were referred for coronary angiography and left heart catheterization for clinical indications. A group of 321 patients with no known significant health problems were enrolled as a control group. Invasive LVEDP measurements were conducted using Millar catheters. The control group was assumed to have a LVEDP = 10 mmHg. The training dataset (n = 262, mean age 45 ± 19 yrs; 54% male) contained 101 patients with LVEDP measurements (n = 44 with LVEDP > 18 mmHg) and 161 controls. The validation dataset (n = 155, mean age 46 ± 21 yrs; 62% male) contained 75 patients with LVEDP measurements (n = 40 with LVEDP > 18 mmHg) and 80 controls.

Results:
Leave-one-out cross-validation on the training dataset yielded a sensitivity of 0.84 (95% confidence interval (CI): 0.70 - 0.93) and a specificity of 0.84 (95% CI: 0.79 - 0.89). The validation dataset showed a sensitivity of 0.80 (95% CI: 0.64 - 0.91) and a specificity of 0.83 (95% CI: 0.75 - 0.90). Figure 1 shows the overall classification performance.

Conclusion:
The Vivio System can accurately detect elevated LVEDP and has the potential to significantly improve early detection of HF in the outpatient setting.
Abstract 16545: Effect of Residual Risk of Inflammation and Lipoprotein(a) on Adverse Cardiovascular Outcomes in Optimally Treated Patients According to Glucose Tolerance Status
Authors: Wang Peizhi , Yuan Jinqing
Published: December 2023

Introduction:
Currently, risks of residual inflammation and residual lipoprotein(a) [Lp(a)] remains in patients with coronary artery disease (CAD) even after lipid-lowering therapy. Hypothesis: This study aims to investigate the association between dual residual risk of inflammation and Lp(a) and adverse cardiovascular events in a large, multicenter cohort with CAD, which has not been investigated.

Methods:
A total of 3,546 patients with CAD were consecutively enrolled. Based on the Lp(a) and hypersensitive C-reactive protein levels, patients were divided into those with no residual risk, residual Lp(a) risk (RLR), residual inflammatory risk (RIR), and residual cholesterol and inflammatory risk (RLIR). All patients were followed for the major adverse cardiovascular events (MACEs), including all cause mortality, non-fatal myocardial infarction, and non-fatal stroke. Multivariable Cox proportional hazard model was conducted to determine hazard ratio (HR) of MACEs for RIR, RCR, and RCIR with different glucose tolerance status.

Results:
Over an average of 2.01 years follow-up, 326 MACEs were recorded. Multivariate Cox analysis showed that higher RIR were significantly related to an increased risk of MACEs, while elevated RLR were associated with a slightly but non-significantly increased MACEs risk. Moreover, when participants were subgrouped according to RLR, RIR and glucose tolerance status together, High RLR+High RIR+Diabetes group had significantly higher risk of MACEs [hazard ratio (HR) 2.93, 95% confidence interval (CI) 1.71-5.02] compared with the reference group (Low RLR+Low RIR+Non-diabetes).

Conclusions:
The combination of RLR, RIR and glucose tolerance status potentiated the adverse effect on MACEs among statin-treated patients with CAD, suggesting that multiple residual risk factors assessment may be a better strategy to improve stratification in very-high risk population.
Abstract 16555: Neutrophil to Lymphocyte Ratio: A Marker of Inflammation in Pericardial Disease
Authors: Bayat Aqieda , Syed Alveena , Ali Ambreen F , tornekar vineet , Dong Tiffany , Klein Allan L
Published: December 2023

Introduction:
Neutrophil-to-lymphocyte ratio (NLR) reflects the intricate relationship between the innate and adaptive immune systems during inflammatory states. With NLR known to be a sensitive indicator of inflammation, its role as a marker in acute pericarditis is yet to be investigated. Here we describe a rare case of acute pericarditis with an elevated NLR highlighting the potential impact this marker can have within the diagnostic evaluation of pericardial disease.

Clinical Case:
46-year-old male with a past medical history of long QT syndrome, crohn's disease, ankylosing spondylitis, psoriatic arthritis, and histoplasmosis who presented with a four-day history of pleuritic chest pain, fever, and chills. The patient had a recent admission two months prior for pericardial effusion s/p emergent pericardial window. Cultures then showed acute and chronic inflammatory granulation tissue and necrosis with no evidence of malignancy and negative stains for fungal organisms. He was discharged home with ibuprofen without improvement. Upon arrival, the patient was hemodynamically stable with a workup notable for leukocytosis of 13.82x 10
9
/l, elevated CRP of 22.5 mg/dL and ESR of 65 mm/hr. NLR was 7.0. Echocardiography showed preserved ejection fraction with moderate circumferential pericardial effusion (figure A). The patient was started on colchicine in addition to ibuprofen. The cardiac MRI obtained showed evidence of moderate active pericarditis (figure B, C). A decision was ultimately made to start inpatient anakinra with a plan to discharge on triple therapy with colchicine, ibuprofen, and rilonacept.

Discussion:
NLR has the potential to be a novel inflammatory marker in pericardial disease associated with pericardial inflammation and edema. A normal range of NLR is between 1-2, with values higher than 3.0 and below 0.7 considered pathological. Our case highlights the importance of NLR as a diagnostic and prognostic marker of pericardial disease.