bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12573: Step Count, Self-Reported Physical Activity, and Five-Year Risk for Incident Atrial Fibrillation
Authors: Shapira-Daniels Ayelet , Kornej Jelena , Spartano Nicole L , Wang Xuzhi , Zhang Yuankai , Pathiravasan Chathurangi H , Liu Chunyu , Trinquart Ludovic , Borrelli Belinda , McManus David D , Murabito JoAnne , Benjamin Emelia J , Lin Honghuang
Published: June 2023

Background:
Obesity and sedentary lifestyles are known risk factors for atrial fibrillation (AF). Wearable devices such as smartwatches present an opportunity to investigate relations between daily step count and AF risk.

Hypothesis:
Higher daily step count, as measured by wearable devices, will be associated with a smaller five-year risk of AF, as predicted by CHARGE-AF score.

Methods:
Participants from the electronic Framingham Heart Study (eFHS) utilized an AppleWatch. Individuals with diagnosed AF were excluded. Daily step count, watch wear time (hours, days), and self-reported physical activity were collected. Individual five-year risk of AF was estimated using The Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) score. Relation between daily step counts and five-year predicted AF risk was examined with linear regression adjusted for age, sex, and wear time. Secondary analyses examined effect modification by sex and obesity (body mass index ≥30 kg/m
2
), as well as relation between self-reported physical activity and predicted 5-year AF risk.

Results:
We examined 932 eFHS participants (mean age 53±9 years, 61% female) with a median daily step of 7360 (25
th
-75
th
percentile 5841-9060). Most participants (89.2%) had <2.5% CHARGE-AF risk. Every 1000 steps were associated with 0.08% lower CHARGE-AF risk (
P
<0.001). A stronger association was observed in men and individuals with obesity. In contrast, self-reported physical activity was not associated with CHARGE-AF risk.

Conclusion:
Higher daily step count was associated with lower predicted 5-year risk of AF, and this relation was stronger in men and participants with obesity. The utility of a wearable daily step counter for risk reduction for AF merits further investigation.
Abstract 12577: Effect of Mavacamten on Diastolic Function in Patients With Obstructive Hypertrophic Cardiomyopathy: Insights From the VALOR-HCM Study
Authors: Cremer Paul C , Geske Jeffrey B , Owens Anjali T , Jaber Wael A , Harb Serge C , Saberi Sara , Wang Andrew , Naidu Srihari S , Schaff Hartzell V , Smedira Nicholas G , Wang Quing , Lampl Kathy , Sehnert Amy J , Nissen Steven E , Desai Milind Y
Published: June 2023

Introduction:
In the randomized VALOR-HCM study of symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM), mavacamten reduced the need for septal reduction therapy at 16 weeks. Because mavacamten is a cardiac myosin inhibitor that may improve ventricular compliance, this sub-study hypothesized that mavacamten would favorably impact diastolic function.

Methods:
Symptomatic patients on maximally-tolerated medical therapy referred for septal reduction therapy were randomized 1:1 to mavacamten or placebo. Echocardiographic assessment was performed by an independent, blinded core laboratory. Diastolic grade was determined according to ASE guidelines. Between-group comparisons were made from baseline to week 16.

Results:
Among 112 enrolled patients, baseline left atrial volume index (LAVi) was similar (Table). At 16 weeks, mavacamten treatment resulted in a significant reduction in LAVi (-5.2 vs -0.5 with placebo,
p
= .003). Similarly, although lateral E/e’ and septal E/e’ were comparable at baseline, patients treated with mavacamten demonstrated a significant reduction at week 16 (lateral E/e’: -3.5 vs 0.7,
p
<0.001; septal E/e’: -3.3 vs 0.7,
p
< 0.001)(Table). Patients treated with mavacamten were also more likely to improve their diastolic dysfunction grade (31.4% vs 12.8%,
p
= 0.032) (Figure).

Conclusions:
After only 16 weeks of therapy, in a highly symptomatic oHCM population with echocardiographic-guided drug titration, mavacamten improved measures of diastolic function.
Abstract 12585: Flexible Modeling of the Association Between Cumulative Exposure to Low-Dose Ionizing Radiation From Cardiac Procedures and Risk of Hematopoietic Cancer in Children With Congenital Heart Disease
Authors: Hasan Mohammad Sazzad , Liu Aihua , Guo Liming , Abrahamowicz Michal , Kaufman Jay S , Marelli Ariane J
Published: June 2023

Background:
High-dose ionizing radiation is a well-established risk factor for childhood malignancies, including hematopoietic cancers (HC). However, data on the effect of low-dose ionizing radiation (LDIR) from medical imaging is conflicting and scant, especially in the pediatric population with congenital heart diseases (CHD). This study evaluated the association between cardiac LDIR exposure and hematopoietic cancers among children with CHD.

Methods:
A nationwide population-based cohort study was conducted using the Canadian Congenital Heart Disease (CanCHD) database. The study population included children born between 1999 and 2017 with at least one CHD diagnosis in their medical records. The cumulative dose of ionizing radiation corresponding to cardiac diagnostic and therapeutic procedures was quantified considering a 6-month exposure lag. The recency-weighted cumulative exposure (WCE) model, a flexible extension of Cox’s proportional hazards model, was used to assess the association.

Results:
We identified 139,975 children with CHD born between 1999 and 2017 and followed them for 1,388,681 person-years since birth. In this population, 718 hematopoietic cancer cases were observed. Children with HC were exposed to low-dose ionizing radiation earlier in life (median age at first exposure: 6 vs. 10 months; p=0.03) and had more procedures than those without cancer (mean number of procedures: 0.4 vs. 0.2; p<0.001). The cases received higher cumulative LDIR doses than their counterparts (mean dose: 2.3 vs. 1.1 mSv; p<0.001). We observed that cumulative LDIR doses within five years were associated with increased risk of hematopoietic cancer with the maximum association magnitude around 2 years.

Conclusion:
This is the first large population-based study documenting increased risk of HC associated with increased dose and recency of the LDIR exposure among children with CHD. Along with these findings, future studies focusing on detecting a threshold effect will help physicians decide the exposure point at which increased surveillance on LDIR exposure should be initiated.
Abstract 12588: Inflammatory Pathways and High-Risk Coronary Plaque in Obstructive Coronary Artery Disease in The PROMISE Clinical Trial
Authors: Zhao Elizabeth , Giamberardino Stephanie , Pagidipati Neha J , Voora Deepak , Hoffmann Udo , Karady Julia , Ferencik Maros , Foldyna Borek , Douglas Pamela S , Shah Svati H
Published: June 2023

Introduction:
Two-thirds of CV events occur in patients without oCAD; vulnerable plaque (VP) has been implicated in its pathobiology. Inflammation plays a role in atherosclerosis, but the relationships between its pathways and related biomarkers in VP have not been comprehensively evaluated.

Methods:
The PROMISE trial randomized 10,003 patients with stable outpatient chest pain to CTA for coronary imaging vs standard of care. In this substudy, we measured 92 inflammatory proteins using the Olink platform in 1788 PROMISE participants with core-lab interpreted CTA and biospecimens. Principal component analysis (PCA) was used for dimensionality reduction and protein PCA factors were tested for association with a high-risk composite (HRC) phenotype (composed of: oCAD, CAC>400, VP features and/or Leaman score>5). Significant PCA protein factors (FDR q < 0.05) were tested with individual HRC features.

Results:
The cohort was 53% female, had a mean age of 60, and 58% had a HRC phenotype. Of 12 PCA factors, three were significantly negatively associated and one was positively associated with HRC (Figure) including factors related to T-cell dependent responses (factor 6, p<0.0001); cytokines (factor 9, p=0.005); chemokines (factor 5, p=0.01); and IFN-gamma related proteins (factor 3, p=0.04). Only factor 9 was associated with VP (OR: 1.14, 95% CI [1.002-1.28], p=0.04), but attenuated in multivariate models. For individual proteins: SCF, TRANCE, TWEAK, TRAIL and IL8 (OR 0.58-1.27, p=0.001 to <0.001) were most significant, and all but IL8 were negatively associated with HRC.

Conclusion:
Leveraging a trial of individuals with stable chest pain and coronary CTA, we identified a range of inflammatory proteins and related pathways associated with HRC. These results implicate TNF-receptor binding (TRAIL, TRANCE) and cytokine pathways in high risk coronary atherosclerosis and highlight biomarkers with potential clinical utility for identifying high risk individuals.
Abstract 12591: Atrial Fibrillation Detection (Incidence And Accuracy) By Implantable Loop Recorders For The Indications: Cryptogenic Stroke, Syncope, Or Palpitations: A Real World Cohort Study
Authors: Klinkhammer Brent , Gayed Noha , Jamal Sameer , Glotzer Taya V
Published: June 2023

Introduction:
Cryptogenic Stroke (CS), syncope, and palpitations are common indications for implantable loop recorder (ILR) insertion, however the incidence of new-onset atrial fibrillation (AF) in these groups in a real world clinical setting is not well characterized.

Methods:
At a single US center, we evaluated 273 consecutive patients who had a Medtronic Reveal LINQ™ LNQ11 implanted for the indications of CS, syncope, or palpitations from 2016-2021. All patients were followed remotely by Carelink. Patients with known AF were excluded. For each patient with an AF episode ≥ 2 minutes, the longest AF electrogram was adjudicated by an electrophysiologist and a cardiology fellow to confirm or refute the AF diagnosis.

Results:
Mean follow-up time was 21 months. There was no difference in mean age between the 3 groups. True, adjudicated AF was diagnosed more often in patients with palpitations and syncope than in patients with CS (table) [p < 0.001]. The ILR reported AF in 92 patients (all groups), of which only 56 (61%) were adjudicated to be true AF. Of the 20 patients with a longest detected AF episode <6 minutes, only 5 (25%) were true AF . Of the 72 patients with a longest detected AF of ≥ 6 minutes, 51 (71%) were true AF (p < 0.001).

Conclusions:
True, adjudicated AF ≥ 6 minutes was detected in 11% of patients with CS, consistent with prior studies. However, in this real world cohort study, AF ≥ 6 minutes was more likely to be detected in patients with palpitations, followed by patients with syncope. The accuracy of ILR detected AF was significantly improved when the AF episode was ≥ 6 minutes duration.
Abstract 12593: Type 2 Diabetes Mellitus Polygenic Score Predicts New Onset Diabetes in Patients With Established Atherosclerotic Cardiovascular Disease: A FOURIER Sub-Study
Authors: Moura Filipe A , Kamanu Frederick , Wiviott Stephen D , Giugliano Robert , Florez Jose C , Roselli Carolina , Keech Anthony C , Lubitz Steven A , Ellinor Patrick T , Ruff Christian T , Marston Nicholas F , Sabatine Marc S
Published: June 2023

Introduction:
Polygenic scores (PS) have been created to predict the risk of developing type 2 diabetes (T2D). We tested whether a contemporary T2D PS predicts new-onset T2D in individuals with established atherosclerotic cardiovascular disease (ACSVD) and across a range of HbA1c and BMI levels.

Methods:
We analyzed individuals without T2D at baseline with available genotyping data from the FOURIER trial. Genetic risk was characterized using a PS for T2D based on 554 previously identified genome-wide significant single nucleotide polymorphisms. PS was analyzed continuously and categorized as high (top 20%) vs. low (bottom 80%). New-onset T2D was pre-specified and adjudicated centrally according to the American Diabetes Association definitions. HRs were calculated and adjusted for baseline age, sex, BMI, HbA1c, SBP, DBP, HDL-C, and triglycerides.

Results:
The 9115 participants in this study had mean age of 63±9 yrs and 22.5% were women. Mean HbA1c and BMI were 5.6±0.4% and 28.7±5 kg/m
2
, respectively. A total of 641 new-onset diabetes cases occurred over a median of 2.3 years of follow up. T2D PS significantly predicted new-onset T2D (adjusted HR per 1-SD increase 1.13 95% CI 1.04-1.23, P=0.006). The rates of new-onset T2D in the high and low genetic risk categories were 10.8% vs. 6.6 %, respectively (adjusted HR 1.41 95% CI 1.18-1.69, P<0.001, Panel A). The predictive strength of high genetic risk for T2D appeared strongest in those without key clinical risk factors, namely, those without pre-diabetes [HR 2.01 (1.03-3.89); Panel B] and those with normal weight [HR 2.77 (1.65-4.66); Panel C]. There was no treatment interaction with evolocumab for new-onset T2D.

Conclusions:
Within a relatively short follow up, we found that a contemporary T2D PS strongly predicted new-onset T2D in patients with established ASCVD. This genetic risk appeared more discriminatory in those lacking traditional clinical risk factors.
Abstract 12675: A Modified Classification Scheme for Chaga's Cardiomyopathy Incorporating Cardiac Magnetic Resonance Imaging
Authors: Smith Alexandra , Fentanes Emilio , Gore Rosco , Bush Kelvin
Published: June 2023

Introduction:
The public health concerns from Chaga’s disease warrant improved cardiovascular imaging efforts. We present a novel and modified Chaga’s staging classification incorporating cardiac magnetic resonance imaging (CMR) to aid in diagnosing cardiomyopathies (CMs). (Figure 1)

Case Presentation:
An 18 year old asymptomatic military basic trainee screened serology positive for Trypanosoma Cruzi. A native of South Texas, he had frequent exposure to many triatome bugs without any history of chagoma or bites. Electrocardiogram showed sinus bradycardia, first degree atrioventricular delay, right bundle branch block with a left anterior fascicular block. Transthoracic echocardiogram (TTE) demonstrated a preserved left ventricular ejection fraction (LVEF), no wall motion abnormalities or valvular disease. Cardiopulmonary exercise testing demonstrated the trainee prematurely reaching anaerobic threshold. CMR was performed to evaluate specifically for delayed gadolinium enhancement and chamber size derangements for prognostication and military disposition purposes. CMR demonstrated mild left ventricular dilation, LVEF 65%, no late gadolinium enhancement, normal T1 relaxation time of 932 milliseconds, and normal T2 weighted images. The exposure history, positive serologies, electrocardiogram, and early ventricular remodeling were consistent with a Chaga’s dilated CM revealed with CMR improved spatial resolution.

Case Outcome: Military standards currently prohibit cardiomyopathies from entering active duty service. The trainee was discharged and referred for medical therapy.

Conclusions:
We propose that CMR be incorporated into the Chaga’s classification schemes to (1) identify structural disease not apparent by TTE, (2) recognize fibrotic or inflammatory myocardial involvement which is prognosis altering, and (3) diagnose early involvement of CM which could benefit from earlier anti-parasitic therapy.
Abstract 12690: Mavacamten Treatment in Patients With Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: A Pooled Safety Analysis of 5 Clinical Trials
Authors: Fermin David , Saberi Sara , Abraham Theodore P , Olivotto Iacopo , Masri Ahmad , Sehnert Amy J , Minton Neil , Fox Shawna , Bach Richard G
Published: June 2023

Introduction:
Mavacamten, a cardiac myosin inhibitor, is approved by the US FDA for the treatment of adults with symptomatic obstructive HCM. We present results from an integrated analysis of pooled mavacamten safety data from clinical studies in patients (pts) with obstructive and nonobstructive HCM.

Methods:
Pts who received ≥1 dose of mavacamten in phase 2 and 3 studies (PIONEER-HCM [end of study date: Jan 12, 2018]; MAVERICK-HCM [Jan 7, 2020]; EXPLORER-HCM [Jul 1, 2020]) and ongoing extension studies (PIONEER-OLE and MAVA-LTE [data cut-off date: Aug 31, 2021]) comprised the pooled analysis population.

Results:
Data were pooled from a total of 314 unique pts with obstructive (n=260) or nonobstructive (n=54) HCM. Baseline characteristics are shown in the
Table.
Cumulative time on study (parent + extension) was ≥6 mo for 91% of pts. The mean cumulative duration of mavacamten exposure was 20.2 mo (range: 0.3, 42.5; median: 20.7 mo); 5.4% of pts permanently discontinued treatment due to treatment-emergent adverse events (TEAEs). Total cumulative exposure was 527.6 pt-yrs, and the median average daily dose of mavacamten was 5.7 mg. Generally similar proportions of pts on mavacamten vs placebo experienced grade ≥3, serious, or drug-related TEAEs; few pts experienced TEAEs that led to study discontinuation or drug interruption (
Table
). The exposure-adjusted incidence of adjudicated events in EXPLORER-HCM and MAVA-LTE of heart failure and new-onset atrial fibrillation were 1.42 and 3.07 per 100 pt-yrs, respectively. As previously reported, 4 deaths occurred across studies: 3 in the mavacamten arm due to TEAEs (bacterial endocarditis, cardiac arrest, and acute myocardial infarction [all, n=1]), with none considered related to study drug, and 1 in the placebo arm (sudden death).

Conclusion:
Integrated evaluation of existing trial data in HCM show that mavacamten is safe and generally well tolerated, irrespective of the presence of obstruction and across multiple doses.
Abstract 12718: ST Segment Elevation Myocardial Infarction Case With a Novel Therapy
Authors: Karacsonyi Judit , Fukui Miho , Kostantinis Spyridon , Simsek Bahadir , Brilakis Emmanouil S
Published: June 2023

History:
A 78-year-old man presented with anterior ST-segment elevation. Coronary angiography demonstrated an occluded left anterior descending coronary artery (LAD Figure 1A) with stenosis of the left circumflex (Cx) coronary artery.

Procedure:
The LAD was crossed with a workhorse wire (Figure 1B). Predilation restored the flow in the LAD and two diagonal branches (Figure 1C). After assessing the lesion with intravascular imaging (Figure 1D), two drug-eluting stents (DES) were deployed with provisional technique (Figure 1E). The diagonal was rewired and dilated with a 2.0 mm balloon (Figure 1F). A 3.5x20 mm DES was deployed covering the proximal LAD lesion (Figure 1G). The Cx ostium appeared pinched, but the diastolic pressure ratio was 0.95, hence no PCI was performed. Given the large MI size, we administered super saturated oxygen (SSO2). A 5F FR5 catheter was inserted into the LM ostium and SSO2 was administered for 1 hour. An excellent final angiographic result was achieved with TIMI 3 flow and well-expanded stents (Figure 1H). Peak creatinine kinase was 5840 U/l. Magnetic resonance imaging on the next day showed small thrombi, prominent microvascular obstruction in the mid LAD territory, and transmural infarction (Figure 1I). Left ventricular ejection fraction of 39% with normal left ventricular volume. The patient was discharged 3 days later on dual antiplatelet therapy and warfarin and referred to cardiac rehabilitation.

Conclusion:
“Time is muscle”, hence immediate revascularization is essential. Large anterior STEMIs may benefit from SSO2.
Abstract 12743: Patient Satisfaction and Determinants of 1-Year Mortality Following Acute Coronary Syndrome
Authors: Paknikar Sujaytha , Girardo Marlene , Legler Sean , Mora Samia , Alsheikh-Ali Alawi , Dugani Sagar , Zubaid Mohammed
Published: June 2023

Introduction:
The association of patient satisfaction with hospital ACS care and risk for long-term outcomes is incompletely described. This is particularly relevant to the Gulf region, where the ACS burden is high and literature on patient satisfaction and outcomes is lacking. The aim was to compare determinants of 1-year mortality based on patient satisfaction with ACS care in the Gulf region.

Methods:
In a prospective registry of 3566 ACS patients from Bahrain, Kuwait, Oman, and UAE (Gulf COAST registry), we grouped patients by their self-reported overall satisfaction with ACS care reported at 1-month following ACS (low satisfaction [n=1654] vs. high satisfaction [n=1912]; Table). We examined associations of baseline characteristics and risk for 1-year mortality in logistic regression models adjusted for Global Registry of Acute Coronary Events (GRACE) score.

Results:
Mortality at 1-year following ACS was higher in patients reporting low satisfaction (8.8%; n=146/1654) vs. high satisfaction (5.4%; n=103/1912) (
P
<.0001). Women, compared with men, had higher 1-year mortality risk in both satisfaction groups, and statistically significant risk in the low satisfaction group (aOR 1.45 [1.01–2.07];
P
<.05). Lack of employment (vs. any employment) was associated with higher 1-year mortality risk in both the low satisfaction (aOR 6.44 [2.58–16.03]) and high satisfaction (aOR 2.58 [1.35–4.93]) groups with borderline significant interaction (
P
interaction
=

.08). In both satisfaction groups, lack of education, hypertension and prior angina were associated with higher 1-year mortality risk, whereas dyslipidemia and diabetes showed no association.

Conclusions:
Low patient satisfaction with ACS care was associated with higher 1-year mortality risk. Socioeconomic factors such as employment and education were associated with higher 1-year mortality, independent of patient satisfaction, and may guide mortality reduction interventions.
Abstract 12756: Gender Differences in Physical and Depressive Symptoms of Heart Failure in a Propensity Matched Sample
Authors: Roberts Davis Mary , Hiatt Shirin O , Dieckmann Nathan , Hansen Lissi , Gupta Nandita C , Lee Christopher S , Denfeld Quin E
Published: June 2023

Introduction:
There are a number of gender differences in heart failure (HF) care and outcomes; yet there remain gaps in our understanding of gender differences in HF symptoms. The aim of this study was to use propensity matching to examine gender differences in physical and depressive HF symptoms between women and men.

Methods:
Data from 6 studies of unique patients with NYHA Functional Class I-IV HF were combined. Across all studies, physical symptoms were measured with the HF Somatic Perception Scale (HFSPS; including two subscales - Early & Subtle and Dyspnea), and depressive symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9). Using clinical and behavioral characteristics based on prior gender research in HF, a propensity score was derived for each participant. Then, nearest neighbor matching was performed to determine pairs of women and men with similar propensity scores and examined the average treatment effects (ATE) between genders on the symptom measures.

Results:
Nearest neighbor matching yielded 183 matched pairs (n = 366). The average age was 58 years. Common clinical characteristics were: non-ischemic etiology (66%), systolic HF (83%), hypertension (53%), Type II Diabetes (23%), and atrial fibrillation (43%). The average mean difference in symptom scores between women and men (ATE), is displayed in
Table 1.
Women reported lower scores on all symptom measures compared with men; however, this difference was not statistically significant.

Conclusions:
In this propensity matched sample of women and men with HF, there were no significant gender differences in physical and depressive symptom scores. Additional gender-balanced research is needed to elucidate nuances in symptom presentation among women with HF.
Abstract 12779: Serial High-Sensitivity Troponin I and Long-Term Risk of Death in Subjects With Suspected Acute Coronary Syndrome
Authors: Pareek Manan , Kragholm Kristian , Kristensen Anna Meta , Biering-Srensen Tor , Byrne Christina , Fosbol Emil L , Kober Lars , Gislason Gunnar , Olsen Niels T , Bhatt Deepak L , Torp-Pedersen Christian
Published: June 2023

Introduction:
Long-term prognostic implications of serial high-sensitivity troponin concentrations in subjects with suspected acute coronary syndrome (ACS) are unknown.

Hypothesis:
To determine mortality according to high-sensitivity troponin I (TnI) concentrations and their changes from baseline, in patients with suspected ACS.

Methods:
Using Danish registries, we identified individuals with a first diagnosis of myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019 who underwent two high-sensitivity TnI (Siemens TnI Flex® Reagent, 99
th
percentile 45 ng/l) measurements during the same hospitalization. Prognostic implications of serial sampling were examined stratifying subjects for normal and elevated concentrations, and for relative changes of 20% and 50%. Absolute and relative risks for death from any cause at days 0-30 and 31-365 were calculated through multivariable logistic regression with average treatment effect modeling.

Results:
Of the 20,609 individuals included, 2.3% had died at 30 days, while 4.7% of 30-day-survivors died between days 31-365. The standardized risk of death at both 0-30 and 31-365 days was highest among subjects with two elevated TnI concentrations (0-30 days: 8.0%, 31-365 days: 11.1%) and lowest among those with two normal TnI concentrations (0-30 days: 0.5%, 31-365 days: 2.6%). In neither case did relative changes between measurements clearly affect mortality. Nevertheless, among persons who went from a normal to an elevated TnI concentration, 30-day mortality was highest in those with a >50% rise versus subjects with a less pronounced rise (2.2% vs. <0.1%). The Figure shows the standardized absolute risk of death from any cause from days 31-365.

Conclusions:
Among individuals with suspected ACS, those with two elevated TnI concentrations consistently had the highest risk of death. Mortality was very low in subjects with two normal TnI values.
Abstract 12808: Genetic Heart Disease and Gender-Affirming Hormone Therapy in Transgender Individuals: Potential Pro-Arrhythmic Considerations
Authors: Pinsky Alexa M , Asaki S Yukiko , Bains Sahej , Bos Johan M , Etheridge Susan P , Ackerman Michael J
Published: June 2023

Background:
Sex hormones influence the arrhythmogenic risk for various genetic heart diseases (GHDs) including long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and idiopathic ventricular fibrillation (IVF). Although exogenous hormones are used frequently in transgender medicine for gender-affirming hormone therapy (GAHT), the effect of such treatments on sudden cardiac death (SCD) risk in transgender patients with a GHD is unknown.

Objective:
To describe the prevalence and spectrum of transgender patients with GHD and to evaluate the impact of GAHT on the treatment and outcomes of their underlying GHD.

Methods:
We performed a retrospective review of all patients seen and evaluated in Mayo Clinic’s Windland Smith Rice Genetic Heart Rhythm Clinic from January 1999-2022 to identify transgender patients. Clinical notes were reviewed for sex, gender identity, GAHT, and details of their GHD, therapy, and outcomes.

Results:
Among 1990 patients with a GHD, we found 7 patients (0.35%) who self-identify as a gender different from their chromosomal sex (transgender). Specifically, there were 4 patients who identified as transgender women (XY males at birth) and 3 as transgender men (XX females at birth). Five of seven patients (71%) have used forms of GAHT, with 2 patients on estradiol and 3 patients on testosterone. GHDs identified include LQT1 (2 transgender women), LQT3 (1 transgender man), LQT3/BrS overlap syndrome (1 transgender woman), genotype negative LQTS (1 transgender man), CPVT (1 transgender woman), and IVF (1 transgender man). Guideline-directed GHD therapy was optimized, not altered nor escalated, for all patients and no patients were advised against initiating GAHT due to perceived interactions. One of seven patients (transgender man with IVF) experienced a breakthrough cardiac event (BCE) while on GAHT, while the other 6 patients have had no BCEs.

Conclusion:
Although less than 0.5% of patients seen over 20+ years self-identified as transgender, their holistic care must include a careful discussion of the possible cardiac risks associated with GAHT. Additional studies are needed to determine the potential pro-arrhythmic risk of GAHT.
Abstract 12823: Racial Disparities and Geographic Variation in Anticoagulant Treatment Among Medicare Beneficiaries With Non-Valvular Atrial Fibrillation in the United States
Authors: Kang Amiee , Noxon Virginia , Atreja Nipun , Hines Dionne , Jiang Jenny , Ferri Mauricio
Published: June 2023

Introduction:
Little is known about racial disparities and the geographic variation in oral anticoagulant (OAC) use throughout the United States (US) since the approval of direct oral anticoagulants (DOACs) as a safe alternative treatment compared to warfarin for non-valvular atrial fibrillation (NVAF).

Methods:
Patients with NVAF were selected from the US Centers for Medicare & Medicaid Services claims database (01JAN2013 to 31DEC2016). The final population consisted of patients with 12 months of health plan enrollment before and after the NVAF diagnosis and with a baseline CHAD
2
S
2
-VASc ≥ 2. Each patient was assigned a 3-digit zip code based on their primary residence. Results were stratified by race. Geographic variations within each race and differences between races were visualized using ArcGIS Pro software.

Results:
Of the 2,756,097 patients with NVAF and CHAD
2
S
2
-VASc ≥ 2, majority (88.9%) were White, and 6.3% were Black. Age and HASBLED scores ranged from 79 (Black) to 81 (White) and 3.4 (White) to 3.9 (Black), respectively. The CHAD
2
S
2
-VASc and CCI scores ranged from 5.1 (White) to 5.5 (Black) and 3.0 (White) to 4.3 (Black), respectively. In general, Black patients had a higher untreated rate with an OAC than Whites (Figures 1 and 2). There were also geographic variations in treatment rates mostly noted among Whites with lower rates in the mid-west compared to the south and west (Figure 2).

Conclusion:
OAC use by race varies considerably by 3-digit zip code in the US. Higher untreated rates and use of warfarin over DOACs in the Black population indicate a potential target for further research into disparities between races in availability of anticoagulant treatment.
Abstract 12830: Significant Smoking Reduction and the Risk of Cardiovascular Disease (CVD): Prospective Results From the Framingham Heart Study
Authors: Duncan Meredith S , Freiberg Matthew S , Greevy Robert , Kundu Suman , Eden Svetlana , Ramachandran Vasan S , Tindle Hilary A
Published: June 2023

Smoking cessation reduces CVD risk, but whether significant reduction (
>
50%) in cigarettes per day (CPD) decreases CVD risk is unclear. Some prior studies have reported no benefit but are limited by incomplete capture of smoking exposure due to few smoking assessments or short follow-up. We used Framingham Heart Study data to quantify CVD risk benefits of smoking reduction.

We included participants attending at least two exams: 3642 Original cohort starting with their fourth exam (1954-1958) and 3582 Offspring cohort starting with their first exam (1971-1975). Participants were free of CVD at baseline and were followed through 2016 for incident CVD. We updated smoking and other variables every 2 (Original) and 4 (Offspring) years, pooling cohorts for analysis. Using extended Cox regression, we compared CVD risk among 4 categories of person-time: current smoking with significant reduction (CPD reduced by
>
50%); current smoking without significant reduction (maintained, increased, or reduced by < 50%); former smokers (quit during follow up); and never smokers. Models were adjusted for sex and time-varying covariates (age, CPD, years reduced, pack-years smoked, and other traditional CVD risk factors).

Relative to the Offspring, the Original cohort was older (51 vs 44) and had a larger proportion of current smokers (49% vs 36%) but smoked fewer CPD (19 vs 23). During a median follow up of 27 years, 2327 CVD events occurred (4.3% among significant reducers). Compared to current smoking without significant reduction, significant reduction was associated with lower CVD risk (HR [95% CI]: 0.76 [0.58, 0.99]). After excluding smokers who increased CPD, the effect was similar (HR=0.80 [0.60, 1.08] p=0.14). Significant reduction was associated with higher CVD risk compared to quitting smoking (1.57 [1.24, 2.01]) and never smoking (1.45 [1.12, 1.87]).

Significant CPD reduction is associated with lower CVD risk compared to current smoking without significant reduction, but with higher CVD risk compared to quitting and never smoking. These findings incorporate extensive lifetime smoking history, including changes in smoking rate, and provide evidence for public health messaging that, while cessation is preferred, smoking reduction may also decrease CVD risk.
Abstract 12835: Predictors of Utilization of Multi-Vessel Percutaneous Coronary Revascularization vs. Bypass Surgery in Patients Hospitalized With Non-ST Wave Elevation Myocardial Infarction and Comorbid End-Stage Renal Disease: A Nationwide Analysis
Authors: Agarwal Siddharth , Bansal Agam , Akhtar Khawaja , Krishan Satyam , Anwaar Muhammad Faraz , khan Jehanzeb , Garg Nikita , Baber Usman
Published: June 2023

Introduction:
The appropriate strategy for revascularization in patients with coronary artery disease (CAD) and concomitant end-stage renal disease (ESRD) is unknown. The aim of this study was to determine the hospital and patient levels predictors of the type of revascularization strategy pursued in patients hospitalized with non-ST wave elevation myocardial infarction (NSTEMI) and ESRD.

Methods:
Study cohorts were derived from the Nationwide Inpatient Sample (NIS) 2016-19. Study variables were identified using ICD-10-CM-codes. Patients presenting with cardiogenic shock were excluded. The primary outcomes were the predictors of the type of revascularization strategy pursued. Multivariable logistic regression was used to adjust for potential confounders.

Results:
There were a total of 87,800 hospitalizations for NSTEMI with comorbid ESRD, out of which 8060 (53%) underwent multi-vessel PCI and 6909 (46%) underwent CABG. Patients undergoing CABG were younger, had a lower proportion of females, and higher burden of comorbidities (including arrhythmias, coagulopathy, valvular heart disease, morbid obesity, and active drug abuse disorder) than those undergoing MvPCI. Multivariate patient-level and hospital-level predictors are demonstrated in Figure 1. As expected, CABG was associated with significantly higher odds of in-hospital mortality (OR:2.01 (1.3-3.1), p<0.01), length of stay (8.9 days longer, p<0.01), and total hospitalization charges (152,527$ higher, p<0.01) as compared to MvPCI. There was no difference in the odds of stroke between both cohorts.

Conclusion:
Patient-level factors (including female gender, age, comorbidities (arrhythmias, peripheral vascular disease, diabetes, coagulopathy, history of CABG or PCI, prior stroke/TIA), and hospital levels factors (bed size, hospital procedural volume) independently predicted the type of revascularization strategy pursued in patients hospitalized for NSTEMI with ESRD.
Abstract 12839: Integrated Multi-Omics and Single Nucleus Transcriptomics Highlight Enhanced Adaptive Immune Responses in Human Bicuspid Aortic Valve Stenosis
Authors: Blaser Mark C , Reichart Daniel , Sonawane Abhijeet , Schlotter Florian , Halu Arda , Passos Livia Silva A , DeLaughter Daniel , Zhou Wunan , Blankstein Ron , DI CARLI MARCELO , Nunes Maria D , Kaneko Tsuyoshi , robson simon , Body Simon C , Muehlschlegel J Daniel D , Seidman Christine E , Seidman Jonathan G , Aikawa Masanori , Singh Sasha A , Aikawa Elena
Published: June 2023

Introduction:
Bicuspid aortic valve (BAV) is the most common congenital cardiac defect, occurring in 1.5% of humans. Due to unknown pathogenic mechanisms, over 70% of those with BAV develop calcific aortic valve disease (CAVD). These patients require valve replacement 25x more frequently and a decade earlier than those with a tricuspid aortic valve (TAV).

Objective:
Identify cellular and molecular drivers of accelerated disease in BAV-CAVD.

Methods:
Small RNA-seq, RNA-seq, and proteomics were performed on 70 human aortic valves (11 non-diseased TAVs; fibrotic and calcific stages of 32 TAVs and 27 BAVs excised for CAVD). Single nuclei RNA-seq (snRNA-seq) was completed on 54,608 nuclei from 13 additional human valves (4 non-diseased TAVs; 5 TAVs and 4 BAVs with CAVD).

Results:
4,938 miRs, transcripts, and proteins were differentially enriched between stages of BAV- and TAV-CAVD (q<0.05). Multi-omics data, CT-derived valve calcification, and 29 clinical parameters were integrated by latent factor analysis. Protein-protein interaction networks revealed significantly elevated adaptive immune responses in BAV-CAVD: T cell/B cell inflammatory activation was enhanced and SLIT-ROBO signaling disrupted in diseased BAVs. snRNA-seq identified 10 major cell types in human aortic valves: valvular interstitial cells (65% of cells; 3 states), endothelial cells (10%; 2), macrophages (13%), T cells (8%; 2), and B cells (3%; 2). CAVD drove differentiation of dual side-specific endothelial subpopulations, enrichment of CARMN/CACNA1C/ACTA2-high interstitial cells, and substantial immune cell accumulation. B cells were further enriched in BAV- vs. TAV-CAVD.

Conclusions:
Adaptive immunity underpins molecular differences in BAV- vs. TAV-CAVD and is a novel avenue for tailored pharmacotherapy. We potentiate targeting of key cellular subpopulations by defining the dissociation bias-free transcriptional and cellular diversity of human CAVD at single-cell resolution.
Abstract 12848: Infections Requiring Hospitalization in Patients One Year Post Heart Transplant
Authors: Jason Max , Alpizar-Rivas Rodolfo , Palli Rohith , Alexis Jeffrey , Sorensen Anna , Hay Christine
Published: June 2023

Introduction:
Immunosuppression of heart transplant (txp) recipients increases risk of infection. This study will identify the most common pathogens and characterize the most at-risk patients.

Methods:
We performed a single center retrospective cohort study at the University of Rochester. Demographics, pretransplant characteristics, and infections requiring rehospitalization were obtained (table 1) from electronic records of patients who received a txp from January 1, 2011 through July 1, 2020. Chi-square, t-test, and Wilcoxon rank-sum test assessed association between mortality, infection risk and other variables.

Results:
We identified 132 patients who received txp but excluded 4 due to incomplete data, 10 (7.6%) patients died during index admission while 12 (9.4%) more patients died in the year following their txp. Infections occurring 1 month post txp were associated with mortality (p-adj 0.026). Prior sternotomies (n=65, 50.8%) were associated with both mortality and bacterial infection (p-adj <0.01). EBV mismatch (n= 7, 5.5%) was associated with infections during months 7-12 post-txp (p-adj 0.027). Unknown pathogens (20) were the most common cause of rehospitalization followed by Pseudomonas (13) (Fig 1).

Conclusions:
Our study identifies patient risk of rehospitalization due to infection in the year following txp. Prior sternotomies were associated with worse outcomes. We hypothesize this is due to scarring and is worth studying prospectively. Patients with EBV mismatch had higher rates of infections in months 7-12, a finding not previously described. There was higher mortality associated with infections that required hospitalization in the first month.
Abstract 12853: Superiority of Intranasal Over Systemic Administration of a Soluble ACE2 Protein (ACE2 618-DDC-ABD) in SARS-CoV-2 Infected Mice
Authors: Hassler Luise , Wysocki Jan A , Gelarden Ian , Khurram Nigar , Nicolaescu Vlad , Tomatsidou Anastasia , Gula Haley , Randall Glenn , Missiakas Dominique , Henkin Jack , Battle Daniel C
Published: June 2023

Introduction and Hypothesis.
Our group and others are using soluble ACE2 proteins to combat SARS-CoV-2. We have previously reported prevention of mortality, improvement of lung and kidney injury and reduced viral loads in SARS-CoV-2 infected mice that received a novel soluble ACE2 protein with extended duration of action and increased binding affinity for SARS-CoV-2, termed ACE2 618-DDC-ABD. In our previous study, this protein was administered both intranasally (IN) and intraperitoneally (IP). Here we tested the hypothesis that IN is more protective than IP administration.

Methods:
Human ACE2 618-DDC-ABD was tested in a BSL-3 facility in mice transgenic for human ACE2 (k18hACE2), infected with 3x10
4
PFU SARS-CoV-2. One hour before viral inoculation, the first protein dose was administered followed by 2 consecutive doses 24h and 48h post viral inoculation, either IN or IP (n=10 each). Weight, clinical score and mortality were monitored.

Results:
In the vehicle-receiving group (BSA in PBS), mortality was 100% on day 5. By contrast, in the IN-group, mortality was reduced markedly to only 10% on day 5 and 14. In the IP-group, by contrast, mortality was 60% at day 5 and 100% at day 14 (fig). In the IP-group, day 5 clinical scores [median (range)] were worse than in the IN-group [3.0 (2.0) and 1.0 (2.0), respectively, p=0.0032].

Conclusions:
This study confirms the dramatic improvement in survival in mice treated with an improved soluble ACE2 protein and demonstrates the superiority of IN over IP administration.
Abstract 12859: Transcatheter Aortic Valve Implants Using Virtual Reality May Predict Paravalvular Leak in Bicuspid Severe Aortic Valve Stenosis
Authors: Chahine Johnny , Yannopoulos Demetris , Raveendran Ganesh , Gurevich Sergey
Published: June 2023

Introduction:
Preoperative 3-dimensional (3D) planning in transcatheter aortic valve replacement (TAVR) has improved outcomes and reduced adverse events. Moderate and even mild paravalvular leak (PVL) is an important predictor of adverse events. PVL remains a challenge for TAVR in bicuspid severe aortic valve stenosis (AS). Here, we investigate virtual reality (VR) simulated TAVR implants in bicuspid severe AS to predict PVL.

Hypothesis:
VR TAVR simulation may predict PVL in bicuspid severe AS and allow for improved valve selection before TAVR procedures.

Methods:
Patients with bicuspid severe AS treated with TAVR between 2014 and 2018 were included. The aortic root, ascending aorta, and left ventricular outflow tract were reconstructed based on pre-operative computed tomography. A 3D TAVR valve was then inserted into the reconstructed root in VR. The primary endpoint was the percent circumference of valve malapposition in VR (Elucis, Realize Medical) as compared to the severity of PVL on postprocedure echocardiography.

Results:
12 patients were included in this study. The mean age was 69.2 years ± 17 and 41.7% were female. 75% received a 26mm Sapien 3 valve (Edwards Lifesciences) and 25% had a 29 mm Evolut R CoreValve (Medtronic) implanted. Among patients who had no or trivial PVL (n=9), 7 patients had no malapposition on VR and 2 patients had less than 5% malapposition. Both patients with mild PVL had 10% malapposition. The only patient with moderate PVL had 25% malapposition
(table 1, figure 1).
There was 100% agreement between the VR simulated implants and post-procedure PVL measured by echocardiography.

Conclusion:
TAVR implantation in VR may predict PVL in bicuspid severe AS.
Abstract 12865: Is Atrial Fibrillation in HFpEF a Distinct Endotype? Insights From Multiparametric MRI and Circulating Fibroinflammatory Markers
Authors: Dattani Abhishek , Kanagala Prathap , Parke Kelly S , Marsh Anna-Marie , Brady Emer M , Singh Anvesha , Arnold Jayanth R , Moss Alastair J , Squire Iain B , Ng Leong L , Gulsin Gaurav S , McCann Gerry P
Published: June 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) frequently occur in parallel. Whether this coexistence is associated with distinct alterations in myocardial remodelling and mechanics is not known.

Methods:
Adults with heart failure with an LV EF greater than 50% on echocardiography were prospectively recruited as part of the DIAMOND HFpEF study (NCT03050593). Participants underwent phenotyping including a panel of 49 fibroinflammatory plasma biomarkers, echocardiography and comprehensive stress cardiac MRI (CMR). Between group comparisons were adjusted for age, sex, ethnicity, body mass index (BMI), diabetes, systolic blood pressure and estimated glomerular filtration rate (eGFR).

Results:
136 participants were included: sinus rhythm (n=75) and AF (n=61). Patients with AF were older (76
vs.
70 years), less ethnically diverse (minority ethnicity 7
vs.
24%) and had a lower prevalence of diabetes (36
vs.
61%). There were no significant differences in heart rate, blood pressure, BMI, eGFR, HbA1c, E/e’ or B-type natriuretic peptide, but AF patients had higher NTproANP (7704
vs.
5749pg/mL) and shorter E deceleration time (211±60
vs.
259±78ms). On CMR, ventricular volumes, mass, stress myocardial blood flow and myocardial fibrosis were similar, but those in AF had increased atrial volume (61±30
vs.
39±15mL/m
2
), reduced systolic function (LV EF 63±8
vs.
68±8%; global longitudinal strain 13.6±2.9
vs.
14.7±2.4%, p=0.003) but higher diastolic strain rate (0.73±0.28
vs.
0.53±0.17/s, p<0.001). Patients with AF had higher levels of syndecan-1, matrix metalloproteinase-2, proBNP and angiopoietin-2, but lower level of interleukin-8 (p<0.05 for all; Figure 1).

Conclusions:
In HFpEF, AF is associated with lower systolic function but higher diastolic strain rate and a different fibroinflammatory profile compared to sinus rhythm. These findings may suggest that some patients with AF and HFpEF have a distinct endotype.
Abstract 12871: Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Hypertrophic Cardiomyopathy
Authors: Khawaja Tasveer , Majmundar Monil , ZUZEK ZACHARY , Arora Shilpkumar , Ukaigwe Anene C
Published: June 2023

Introduction:
Patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) are at increased stroke risk in comparison to those without HCM. The role of left atrial appendage occlusion (LAAO) in these patients is unclear.

Methods:
In this retrospective cohort study, we identified patients with HCM and AF using the National Readmission Dataset from 2016-19. Patients were stratified based on LAAO status. The primary efficacy outcome was a composite of any stroke (ischemic and hemorrhagic), TIA, and all-cause mortality. The primary safety outcome was a composite of major bleeding and pericardial complications. Individual components of the primary outcomes were secondary outcomes. Patients were matched using inverse probability of treatment weighting. Cox-proportional hazard regression was applied to calculate hazard ratio (HR) with 95% confidence interval (CI) on matched cohorts.

Results:
We identified 71,980 patients with HCM and AF. Of these, 1,351 (1.9%) patients underwent LAAO. Those who underwent LAAO were significantly younger than those who did not (67.5±10.1 years vs. 70.0±13.1 years, p<0.001) and were more likely to be male (54.6% vs. 45.4%). LAAO was associated with a lower risk of the primary efficacy outcome (2.5% vs. 5.4%, HR: 0.38; 95% CI: 0.17-0.88; p=0.024) and the primary safety outcome (2.9% vs. 6.8%, HR: 0.39; 95% CI: 0.23-0.66, p=0.001). LAAO associated with reduced major bleeding (1.6% vs. 6.0%, HR 0.34, 95% CI 0.18-0.64, p=0.001), GI bleeding (0.2% vs. 1.3%, HR 0.22; 95% CI: 0.06-0.79, p=0.02), blood transfusions requiring admission (2.10% vs. 4.90%, HR 0.37, 95% CI 0.19-0.73, p=0.004), and admissions for bleeding (0.50% vs. 2.30%, HR 0.20, 95% CI 0.07-0.58, p=0.003). Pericardial complications were similar in both groups.

Conclusion:
LAAO was associated with a lower risk of stroke and major bleeding in patients with HCM and AF. Future prospective studies on the safety and efficacy of LAAO in concurrent AF and HCM are needed.