bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15333: Use of Wearable Devices by Patients With and At-Risk for Cardiovascular Disease in the United States: A Nationally Representative Study
Authors: Dhingra Lovedeep S , Aminorroaya Arya , Oikonomou Evangelos , Aghajani Nargesi Arash , Khera Rohan
Published: June 2023

Background:
Wearable technologies have increasingly been leveraged for management of cardiovascular disease (CVD) and present avenues for artificial intelligence-driven innovation. To evaluate the equitability of their potential impact, we evaluated their adoption in a nationally representative study.

Methods:
Using the nationally representative Health Information National Trends Survey (HINTS) study for 2019-2020, we examined the self-reported use of wearable devices among both patients with CVD (ischemic heart disease or heart failure) and those with risk factors (hypertension, diabetes, smoking, and/or obesity). We evaluated the patterns of their use across demographic subgroups of age, sex, race, income, and education as well as the willingness to share data for healthcare applications.

Results:
Of the 9303 individuals in HINTS, 933 had CVD (69±14 years, 47% women) and 5,185 were at risk of CVD (59±16 years, 58% women). An estimated 3.6 million individuals in US with CVD (18% of CVD, 95% CI: 14-29%) and 34.4 million (26% of at-risk, 95% CI: 24-28%) at-risk of CVD used wearables, compared with an estimated 29% of the total US population. Despite representing 49% and 22% of the CVD and at-risk populations, only 12% and 14% patients over 65 years had any wearable use, compared with 17% and 25% in 50-64 year, and 33% for both in 18-49-year group. Further, a higher annual household income and educational attainment was associated with 3- to 4-fold higher wearable use (Table). However, among users, 81% (95% CI: 76-85%) of the patients at risk of CVD would favor sharing wearables data to improve their care without differences across demographic subgroups.

Conclusion:
Demographic subgroups with the known worse cardiovascular outcomes have the lowest use of wearable devices among patients with or at risk of CVD. Unless wearables are supported as health devices, their disparate uptake is likely to further exacerbate disparities in patient outcomes.
Abstract 15342: Predictive Value of Glucose Levels in Patients Suffering From Cardiogenic Shock Complicating Myocardial Infarction
Authors: Buerke Michael , Boettger Priyanka
Published: June 2023

Hypothesis:
Elevated glucose levels on admission are common in patients with acute coronary syndrome (ACS) and have been shown to be a strong predictor of adverse outcome in both diabetic and non-diabetic patients.

Methods:
The purpose of the study was to assess the impact of admission glucose levels on hospital mortality in patients with infarction related cardiogenic shock. Blood glucose levels were measured from first available routine blood specimens up to 96 hours.

Results:
We identified 40 patients with myocardial infarction related cardiogenic shock treated at our university hospital. 45 % of the population had an admission glucose level <6 mmol/L, 15 % had levels from 6 mmol/L up to 11 mmol/L and 40% above 11 mmol/L. In-hospital mortality rate was higher in patients with increased admission glucose levels (<6, 6-11, and ≥11mmol/L: 27,8 %, 66,7 % and 62,5 % respectively, p <0.001). Similarly, significant mortality rate differences were observed in patient subgroups stratified by admission glucose level, presence of diabetes mellitus and cardiogenic shock. Additionally, a reduction of elevated blood glucose levels within six hours to near-normal values resulted in a favorable outcome (reduction within 6 hours vs. not within 6 hours: 25 % vs. 45 %, p<0.05). Interestingly Predictors of in-hospital mortality were age, admission glucose levels, diabetes mellitus, and renal failure.

Conclusions:
Blood glucose level on admission is a strong predictor of in-hospital mortality in patients with infarction related cardiogenic shock. Impact of admission glucose level on mortality is independent from clinically manifested diabetes and cardiogenic shock presence. Further analysis showed better survival in patients whose elevated blood glucose levels were reduced within 6 hours to normal or near-normal ranges.
Abstract 15346: Outcomes of Conduction System Pacing in Patients With Cancer and Cardiomyopathy
Authors: Skeete Jamario R , Dunleavy Michael , Chu Jian , Sharma Parikshit S , Rosado Melanie , Okwuosa Tochi , Santos Volgman Annabelle S
Published: June 2023

Introduction:
Conduction System (His-Bundle, Left Bundle Branch) Pacing (CSP) for cardiac resynchronization therapy (CRT) provides more physiologic ventricular activation than right ventricular pacing. CSP has demonstrated improved outcomes in patients with cardiomyopathy. The effectiveness of CSP in patients with cancer or prior exposure to cardiotoxic agents is unknown.

Methods:
We retrospectively studied patients with cancer who underwent CSP for CRT from January 2018 to June 2021 at Rush University Medical Center. Changes in QRS duration, left ventricular ejection fraction (LVEF), B natriuretic peptide (BNP), and hospital admission rates pre- and post-initiating CSP were analyzed at baseline compared with one-year post CSP using student’s T-Tests.

Results:
Sixty-five patients with cancer underwent CSP, of which 11 had cardiomyopathy and underwent CSP for CRT. Five patients (45.5%) were female, 5 (45.5%) Caucasian, with mean age 71.2± 9.0 years. Non-Hodgkin Lymphoma (3 cases, 27.3%) was the most common cancer. Most (90.1%) patients had non-metastatic disease, 72.7% had prior chemotherapy, 54.5% were treated with cardiotoxic agents. Seven patients (63%) had a baseline left bundle branch block (LBBB). QRS duration shortened (122.3 ± 18.9 ms. vs. 153.7 ± 20.6 ms, p=0.003), LVEF increased (27.0 ± 6.2% vs. 39.0 ± 12.9 %, p=0.007), and BNP decreased (807.6 ± 1709.9 pg/ml vs. 591.4.0 ± 1079.4 pg/ml, p=0.78) (figure1). There was no change in heart failure hospitalizations (0.3 ± 0.48 admissions /person/year), at baseline vs. 1-year post-CSP.

Conclusion:
In this small population of patients with cancer and reduced LVEF with indications for CRT, CSP was associated with significant improvement in LVEF and QRS duration; and a non-significant decrease in BNP. The overall hospitalization rate was very low. Future studies in a larger population with a longer follow-up period are paramount to further assess this promising strategy.
Abstract 15355: Evaluating the Electrocardiographic Characteristics of Transgender Patients Undergoing Gender-Affirming Hormone Therapy With Artificial Intelligence
Authors: Sang Philip , Adel Fadi , Maheshwari Arvind , Mangold Kathryn , Attia Zachi , Cummings Paige , Davidge-Pitts Caroline , Lopez-Jimenez Francisco , Friedman Paul , Noseworthy Peter A , Mankad Rekha
Published: June 2023

Evaluating the Electrocardiographic Characteristics of Transgender Patients Undergoing Gender-affirming Hormone Therapy with Artificial Intelligence

Introduction:
An artificial intelligence (AI) electrocardiogram (ECG) algorithm has been demonstrated to identify a patient’s birth designated sex with 90.4% accuracy with an AUC = 0.97. However, the algorithm has not been evaluated in transgender and gender diverse individuals. We aimed to determine how the algorithm output varies among transgender individuals seen at the Mayo Clinic Transgender and Intersex Specialty Care Clinic (TISCC) who are undergoing gender-affirming hormonal treatment (GAHT).

Methods:
We applied the algorithm (which assessed the probability of “male” between 0 and 1, with < 0.5 considered as “female” and > 0.5 as “male”) to ECGs obtained from patients in the TISCC before and after the initiation of GAHT. GAHT frequently involves the use of testosterone in transgender men, and estrogen and anti-androgen agents in transgender women. Patient characteristics, including the date of the initiation of GAHT, were collected through chart review.

Results:
Among transgender women, the AI model probability of “male” decreased from 0.84± 0.25 (12/86 classified as males) to 0.59±0.36 (68/173 classified as male) with GAHT (p < 7.8e-10). Among transgender men, the AI model probability of “male” increased from 0.16 ± 0.28 (7/47 classified as male) to 0.41 ±0.38 (22/53 classified as male) with GAHT (p < 2.4e-4).

Conclusion:
After GAHT initiation, the Mayo Clinic AI ECG algorithm assigns a higher probability of being male among transgender men and a lower probability of being male among transgender women. These findings warrant further investigation into the electrocardiographic differences across genders and the effects of GAHT on the human heart.
Abstract 15360: Characteristics and In-Hospital Outcomes of Patients Undergoing Pulmonary Vein Isolation With and Without Adjunctive Lesions: Insights From the Ncdr Afib Ablation Registry
Authors: Darden Douglas J , Aldaas Omar M , Du Chengan , Feld Gregory K , Pothineni Krishna , Gopinathannair Rakesh , Lakkireddy Dhanunjaya R , Curtis Jeptha P , Freeman James V , Akar Joseph , Hsu Jonathan C
Published: June 2023

Introduction:
The optimal ablation strategy beyond pulmonary vein isolation (PVI) for atrial fibrillation (AFib) is undefined. No prior study has been adequately powered to evaluate real-world safety outcomes in those receiving adjunctive (adj) ablation lesions. We sought to evaluate characteristics and in-hospital complications among patients undergoing AFib ablation with PVI with and without adj lesions.

Hypothesis:
PVI + adj will be more common in those with persistent AF (persAF) and be associated with adverse events.

Methods:
Patients enrolled in the National Cardiovascular Data Registry AFib Ablation Registry undergoing first-time ablation between 2016 and 2020 were stratified into paroxysmal (PAF) and persAF, and separated into PVI only, PVI+cavotricuspid isthmus (CTI) ablation alone, PVI+adj (SVC isolation, coronary sinus, vein of Marshall, atypical atrial flutter lines, other). In-hospital outcomes were compared using multivariable logistic regression.

Results:
A total of 50,937 patients were included. Among PAF, as compared to PVI only, both PVI+CTI and PVI+adj were associated with prolonged hospitalization after adjustment, while there were no differences in complications. In the persAF cohort, as compared to PVI only, PVI+adj was associated with a higher risk of any complication and major complication, while no differences were observed in PVI+CTI (Table). In-hospital death was rare with no differences across groups.

Conclusion:
Adjunctive lesions are commonly performed in real-world practice in both PAF and persAF with varied strategies. Among PAF, additional lesions were associated with prolonged hospitalization, although not complications. Among persAF, PVI+adj, but not PVI+CTI, was associated with a higher risk of complications. While additional CTI ablation may be considered safe in persAF, further efforts to determine optimal ablation strategies beyond PVI and mitigate risk are warranted.
Abstract 15372: Machine Learning Distinguishes Continuous Risk of Gastrointestinal Bleeding, Stroke, and Death in Ambulatory Lvad Patients
Authors: Shah Palak , Sayer Gabriel T , Sinha Shashank S , Kanwar Manreet , Cowger Jennifer , Pagani Francis D , Nayak Aditi , Mehra Mandeep , Cleveland Joseph C , Psotka Mitchell , Singh Ramesh , Desai Shashank , Lu Qianhui , Hu Yajing , CONNOLLY ALLISON T , Kormos Robert , Uriel Nir
Published: June 2023

Introduction:
Advanced data analytics are needed to reliably predict bleeding and thrombotic risk in ambulatory left ventricular assist device (LVAD) patients.

Hypothesis:
Machine learning techniques can be used to predict risk of gastrointestinal bleeding (GIB), stroke, or death in ambulatory LVAD patients.

Methods:
HeartMate 3
TM
LVAD recipients from the MOMENTUM 3 studies with up to 2-year follow-up were included. A multistate model was developed with 5-fold cross-validation to characterize the continuous probability of events after discharge. Model features included pre-implant, index implant, and short- and long-term post-implant clinical features. 85% of patients were used for model derivation and 15% for validation. Model performance was assessed with area under the curve (AUC). With the model features, a risk stratification tool was created by dividing patients’ into terciles of predicted risk.

Results:
Among 2,056 LVAD patients who survived to hospital discharge, the median age was 59.4 yrs (20.4% Female, 28.6% Black). At 2-years, the incidence of GIB, Stroke, and Death was 25.6%, 6.0% and 12.3%, respectively. Unique models including pre-implant, implant and post-implant features were created for GIB (Figure A), Stroke and Death. In ambulatory LVAD patients, the model could predict 30-day risk of GIB at any time post-implant which was 26.9%, 2.6% and 0.8% in high, medium and low-risk patients respectively (Figure B). Similar risk prediction was performed for stroke and death. The cross-validated AUC in the derivation cohort was 0.70, 0.69, and 0.85 for GIB, stroke, and death respectively.

Conclusion:
We developed an innovative risk tool informed by machine learning techniques that predicts risk of GIB, stroke, and death at any 30-day interval in ambulatory LVAD patients with readily available clinical data. The model allows for risk stratification that accurately predicts future events and may be useful to guide clinical decision making.
Abstract 15393: Low Risk of Rheumatic Heart Disease Among Children Found to Have an Alternate Diagnosis to Acute Rheumatic Fever in a High Risk Setting
Authors: Pulle Jafesi , Ndagire Emma , Fall Ndate , Nakagaayi Doreen , Okello Emmy , Rwebembera Joselyn , Sable Craig A , Sarnacki Rachel , Wirth Scott , Carapetis Jonathan , Beaton Andrea Z
Published: June 2023

Introduction:
In 2015, the American Heart Association revised the Jones Criteria, the gold standard for diagnosis of acute rheumatic fever (ARF). This revision included changes to increase the sensitivity for ARF in high-risk settings. The objective of this study was to determine if there were children who were found to be ARF-negative by strict application of these criteria in a high risk setting but found to have rheumatic heart disease (RHD) on follow-up evaluation.

Methods:
Between 2017 and 2020, we conducted an epidemiological study to determine the incidence of ARF in Uganda. Children and adolescents, 3-17 years, presenting with clinical concern for ARF (fever and joint pain, suspicion of carditis, or suspicion of chorea) were enrolled and evaluated using the Jones Criteria. Children ultimately found to have a laboratory-confirmed alternate diagnosis and those who did not meet ARF criteria but had an unknown final diagnosis, were asked to participate in a longitudinal echocardiographic follow-up study to monitor for development of RHD. Presence of RHD was considered a false negative test and used to calculate the false negative error of not receiving a diagnosis of ARF.

Results:
There were 351 children determined to have an alternate diagnosis during the study period; 180 with a laboratory confirmed final diagnosis (127 malaria, 20 non-rheumatic cardiac disease, 15 influenza, 18 other) and 171 with an unknown final diagnosis. Of these, 220 (62.7%) had at least one follow-up visit (median 366 days, range 10-1054). One child (1/220, <1%) developed echocardiographic evidence of borderline RHD during the follow-up period. Diagnostic overlap (met Jones Criteria but found to have a laboratory confirmed alternate diagnosis) was seen in 18% (33/180) of those with laboratory confirmed alternate diagnosis. Of these, 21 of 33 attended at least one follow-up (median 340 days, range 10-1054), and none showed echocardiographic evidence of RHD.

Conclusions:
Application of the 2015 Jones Criteria showed an exceptionally low rate of subsequent RHD, even in cases of diagnostic overlap. Clinicians working in ARF-endemic settings can have high confidence that children who do not meet criteria for ARF have a low risk of false negative diagnosis and short-term risk of RHD.
Abstract 15395: Caveolin-1 is a Primary Determinant of Endothelial Stiffening Associated With Dyslipidemia, Disturbed Flow and Ageing
Authors: Le Master Elizabeth , Aguilar Victor , Paul Amit , Lazarko Dana , Ahn Sang Joon , Lee James , Minshall Richard D , Levitan Irena
Published: June 2023

Objective:
Endothelial stiffness is emerging as a major determinant in endothelial function. Here, we analyzed the role of caveolin-1 (Cav-1) in determining the stiffness of endothelial cells exposed to oxidized low density lipoprotein (oxLDL) under static and hemodynamic conditions
in vitro
and of aortic endothelium
in vivo
in mouse models of dyslipidemia and ageing.

Approach and Results:
Elastic moduli of cultured endothelial cells and of endothelial monolayer of freshly isolated mouse aortas were measured using atomic force microscopy. We found that a loss of Cav-1 abrogates the uptake of oxLDL (n=5-8) and oxLDL-induced endothelial stiffening (n=4-5) but has no effect on endothelial stiffness in the absence of oxLDL (n=4). A loss of Cav-1 also abrogated endothelial stiffening induced by disturbed flow, which in turn is oxLDL dependent (n=6). Mechanistically, Cav-1 is required for the expression of CD36 (cluster of differentiation 36) scavenger receptor (n=4) but not for endothelial stiffening induced by a direct application of 7ketocholesterol (n=8). Genetic deletion of Cav-1 also led to profound changes in endothelial stiffness
in vivo
: it abrogated endothelial stiffening observed in the disturbed flow region of the aortic arch (n=5-6), abrogated endothelial stiffening induced by feeding the mice high fat diet (4-6 weeks, n=5) and significantly blunted endothelial stiffening that develops with advanced age (n=5-6). This effect was independent of stiffening of the sub-endothelium layer (n=5-8).

Conclusions:
Taken together, this study demonstrates that Cav-1 plays a critical role in endothelial stiffening induced by oxLDL
in vitro
and by dyslipidemia, disturbed flow and ageing
in vivo
. Mechanistically, Cav-1 regulates endothelial stiffening via CD36-mediated uptake of oxLDL, whereas exposure to 7ketocholesterol circumvents this step.
Abstract 15417: Dual Ampk Activator/mtor Inhibitor Improves Metabolic Parameters in T2d Mice and Protects Cardiomyocytes Against Ischemic Injury
Authors: Kraskauskas Donatas , Ni Bin , Mauro Adolfo G , Lau Valerie , Kodali Varun , Samidurai Arun , Belka Igor , Corral Laura , Chan Kyle W , Swindlehurst Cathy A , Salloum Fadi N , Das Anindita
Published: June 2023

Background:
Type 2 diabetes (T2D) is a major metabolic disorder associated with increased morbidity and mortality, predominantly due to heart failure resulting from superimposed ischemic heart disease. Dual AMPK activation/mTOR inhibition (NovoMedix compound, NMX2) has been shown to attenuate adverse cardiac remodeling and fibrosis in a pressure-overload mouse model of heart failure. Given the importance of AMPK signaling in T2D, we investigated the beneficial effects of chronic treatment with NMX2 in T2D mice.

Methods & Results:
Adult male db/db T2D mice were treated daily with NMX2 (50 mg/kg, p.o.) or equal volume of vehicle (7% DMSO, as control) for 15 weeks. Increase in body weight was significantly attenuated along with reduction in insulin levels with NMX2 treatment as compared to control (
A-B
). NMX2 treatment improved glucose homeostasis (glucose and insulin tolerance tests) and reduced adiposity (fat mass percentage, measured by body composition analysis) (
C-G
). Respiratory exchange ratio (RER) measured by indirect calorimetry analysis (Phenomaster, TSE) was significantly improved in NMX2-treated mice, which indicates increased glucose utilization as compared to control mice (
H & I
). Cardiomyocytes isolated from control and NMX2-treated db/db mice were subjected to simulated ischemia/reoxygenation (SI/RO, 40 minutes SI and 1 hour RO). NMX2 significantly reduced necrosis (trypan blue staining,
J
), apoptosis (TUNEL assay,
K
) and activation of the NLRP3 inflammasome (apoptosis speck-like protein, ASC aggregation by immunofluorescence staining,
L & M
) in cardiomyocytes compared to control.

Conclusion:
Chronic treatment with NMX2 improves glucose homeostasis and RER and reduces adiposity and body weight in diabetic mice. NMX2 also protects cardiomyocytes from diabetic mice against ischemic injury by reducing sterile inflammation, which supports the development of this treatment modality for T2D and its related cardiac complications.
Abstract 15435: Evaluating Sex-Disparities in Machine Learning Decision Support Tools for Acute Coronary Syndrome Classification in the Emergency Department
Authors: Bouzid Zeineb , Faramand Ziad , Al-Zaiti Salah S , Sejdic Ervin
Published: June 2023

Introduction:
Women are less likely than men to be promptly diagnosed with acute coronary syndrome (ACS) and have worse post-ACS outcomes. These diagnostic failures are partially due to ACS findings on surface ECG manifesting differently in women, which may result in unnecessary delays in treatment. To narrow health disparities, we aim to investigate the sex-specific signatures of ACS as they appear on ECGs.

Methods:
This was a prospective observational cohort study of chest-pain patients evaluated for suspected ACS at 3 UPMC-affiliated tertiary care hospitals. After featurization, all ECG data were separately fed into 7 machine learning classifiers to predict ACS. We examined the results by sex. We also investigated two other methods: (1) building two independent models based respectively on the female and male subgroups and (2) building a model based on the initial total sample supplemented by the patients’ sex. We used Shapley values to explain the decision-making criteria of the models. We report the results for random forest, the best performing classifier.

Results:
Our sample consisted of 4132 patients (Age 59 ± 16; 47% female; 15% ACS). Machine learning models continue to disproportionately underperform in females across all classifiers evaluated. The sensitivity, specificity and false negative rate in the global model blinded to sex were 82.89%, 76.22% and 17.11% for men, and 67.39%, 74.16% and 32.61% for women (p<0.0001). This statistically significant gap could not be alleviated by building sex-specific models or feeding sex to the input of the model. Indeed, the rate of false negatives in sex-specific models and global models with sex as input were 14.67% and 18.42% for men, and 34.04% and 32.61% for women (p<0.0001). The explainability analysis of the sex-specific models revealed that STT configuration in lateral leads is most informative in women, whereas STT configuration in all leads and particularly in anterolateral leads most informative in men.

Conclusions:
Machine learning models display crucial sex differences in the ACS signatures on the ECG that consistently put women in a detrimental situation. The alternative methods investigated here are not adequate solutions for this disparity. Thus, further investigations should be conducted.
Abstract 15443: Association Between Central Sleep Apnea and P2y12 Inhibitors in Patients With Coronary Heart Disease
Authors: Tzeng William S , Klein Christian , Roth Robert , Cho Yeilim , Munagala Rohit , Healy William , Lobo Jennifer , Mazimba Sula , Kwon Younghoon
Published: June 2023

Introduction:
Central sleep apnea (CSA) is common in patients with heart failure and is associated with a poor prognosis. A number of studies have linked the P2Y12 inhibitor, ticagrelor, with CSA. We aimed to evaluate CSA prevalence in patients with coronary heart disease (CHD) and whether ticagrelor use is associated with CSA in this population.

Methods:
We reviewed consecutive patients with CHD data who underwent a clinically indicated polysomnography (PSG) test over a 5-year period from three academic sleep centers. We sampled patients who were on ticagrelor or clopidogrel during their PSG test at a 1:4 ticagrelor:clopidogrel ratio. Patients with an active opioid prescription at time of PSG test were excluded. Age, left ventricle (LV) dysfunction (ejection fraction <45%), and P2Y12 inhibitor use were included in a multivariate logistic regression.

Results:
A total of 141 patients (age 63.7 ± 11.4, 33% female) were included with 30 on ticagrelor and 111 on clopidogrel. 106 (75.2%) patients had undergone percutaneous coronary intervention for ACS. 33 (23.4%) patients had LV dysfunction. The mean apnea hypopnea index (AHI) was 29 (/hr). High CSA burden (central apnea index [CAI] ≥5/h) and strict CSA (AHI ≥5/h and CAI >50% of AHI) were present in 16 (11.3%) and 5 (3.5%) patients, respectively. High CSA burden and strict CSA were more common in patients on ticagrelor than in those on clopidogrel (7 [23.3%] vs. 9 [8.1%] and 3 [10.0%] vs. 2 [1.8%]). In multivariable analysis ticagrelor use was associated with high CSA burden adjusting for LV dysfunction and age (OR 3.27, 95% CI 0.99-10.7, p=0.048). No variables were associated with strict CSA.

Conclusions:
Ticagrelor use was associated with high CSA burden in patients with coronary heart disease. Future studies should verify these results in a larger cohort and explore their clinical significance.
Abstract 15451: Using Fitbit Measured Activity Levels as an Indicator of New York Heart Association (nyha) Functional Class
Authors: Tang Zhengxin , Gerber Ben , Pressler Susan J , Chen Jinsong , Buchholz Susan , Kansal Mayank M , Ruppar Todd , ARRINGTON JASMINE , Owoyemi Ayomide , Leigh Jonathan , Kitsiou Spyros
Published: June 2023

Introduction:
Commercially available wearable devices for physical activity (PA) monitoring may provide objective data to facilitate assessment of NYHA class in patients with heart failure (HF). However, there is limited research exploring their ability to differentiate patients between NYHA classes.

Objective:
This study aims to assess the relationship between NYHA class and PA using a Fitbit wrist-based activity tracker (Charge 3) in patients with HF.

Methods:
We conducted a secondary analysis of baseline NYHA and PA data (daily step count and minutes of moderate-to-vigorous PA [MVPA]) collected by the iCardia4HF trial, which examined the feasibility and preliminary efficacy of a mHealth intervention for HF self-care. NYHA class was determined by a trained research assistant at the baseline visit, using standardized criteria. Daily steps and MVPA minutes were measured using Fitbit data from the first 7 days after the baseline visit. To be included in the analysis, patients had to have ≥4 days with ≥600 minutes of Fitbit wear-time/day.

Results:
We analyzed data from 78 participants (mean age=55.2 years [SD 10.6]; female=43.6%; Black/African American= 79.5%; mean BMI=35.6 kg/m2 [SD 8.7]; HFrEF=65.4%). The Kruskal-Wallis test demonstrated significant differences in the distribution of daily steps (p=.021) and MVPA (p=.023) across NYHA classes. Pairwise comparisons showed that patients in NYHA Class III had significantly lower daily steps and MVPA minutes than patients in Class I. There were also important differences in daily steps and MVPA between patients in NYHA Class III and II, and Class II and I, but these did not reach statistical significance.

Conclusions:
There was a general decrease in steps and MVPA duration with increasing NYHA class. Wrist-worn activity trackers represent a promising method for estimating NYHA class and assessing HF severity and progression through continuous PA monitoring, but larger studies are needed for validation.
Abstract 15459: High Intensity Interval Training versus Moderate Continuous Training in Patients With Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis
Authors: Siddiqi Tariq J , Usman Muhammad Shariq S , Rashid Ahmed Mustafa , Siddiqi Ahmed K , Kamimura Daisuke , Pandey Ambarish , LAVIE Carl J , Mentz Robert J , Butler Javed , Hall Michael E
Published: June 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is a common condition with one of its characteristics being exercise intolerance, which contributes to poor quality of life and clinical outcomes. High-intensity interval training (HIIT) is an innovative training approach, but its impact on patients with HFpEF is uncertain. We pooled data from all relevant studies reporting results of HIIT versus moderate continuous training (MCT) on cardiopulmonary exercise outcomes in patients with HFpEF.

Methods:
PubMed and SCOPUS were queried until February, 2022 for all randomized controlled trials (RCT) comparing the effects of HIIT versus MCT on outcomes such as peak oxygen consumption (peak VO
2
), respiratory exchange ratio (RER), and minute ventilation / carbon dioxide production (VE/CO
2
)> slope. A random-effects model was used and weighted mean differences (WMDs) were reported with 95% confidence intervals (CI). Heterogeneity across studies was evaluated using the Higgins
I
2
statistic.

Results:
Three RCTs (n = 150) were included in our analysis. The mean training duration was 23 weeks (range: 4 - 52 weeks). Pooled analysis demonstrated that HIIT significantly improved peak VO
2
(WMD = 1.46 mL.kg
-1
.min
-1
(0.88, 2.05);
p
<0.00001;
I
2
=0%; Figure 1a), as compared to MCT in patients with HFpEF. However, no significant differences were demonstrated between HIIT and MCT, for RER (WMD = -0.10 (-0.32, 0.12);
p
=0.38;
I
2
=0%; Figure 1b), and VE/CO
2
slope (WMD = 0.62 (-1.99, 3.24);
p
=0.64;
I
2
=67%; Figure 1c).

Conclusions:
Our study demonstrates that HIIT, compared to MCT, had a significant impact on improving peak VO
2
, without evidence of significant benefits on VE/CO
2
slope. Larger trials of exercise training in HFpEF may consider peak VO
2
as a key outcome measure in addition to clinical events. Nevertheless, these improvements in peak VO
2
with HIIT could translate into improvements in quality of life and clinical outcomes in patients with HFpEF.
Abstract 15493: The Efficacy of Cardiac Myosin Inhibitors versus Placebo in Patients With Symptomatic Hypertrophic Cardiomyopathy
Authors: Yassen Mohammad , Burmeister Cameron , Changal Khalid
Published: June 2023

The Efficacy of Cardiac Myosin Inhibitors Versus Placebo in Patients with Symptomatic Hypertrophic Cardiomyopathy.

Introduction:
Given the interplay between hypertrophic cardiomyopathy, elevated resting LVOT gradients (≥ 50 mm Hg) and heart failure and cardiovascular death, cardiac myosin inhibitors have recently emerged as a promising novel therapy to improve HCM-related outcomes by regulating myocardial relaxation and contractility, and thereby reducing intracavitary gradients.

Methods:
We performed a literature search using PubMed, Embase, and Cochrane Library from inception through May 2022 to assess the impact of novel cardiac myosin inhibitors (Mavacamten and Aficamten) on resting and Valsalva LVOT gradients and functional capacity in patients with symptomatic hypertrophic cardiomyopathy. The co-primary outcomes were mean percent change from baseline in resting LVOT gradient and Valsalva LVOT gradient, as well as patients achieving NYHA Class Improvement ≥ 1. Secondary outcomes included mean percent change from baseline NT ProBNP, Troponin I, and LVEF.

Results:
4 studies (all randomized-control trials, including 3 Mavacamten-focused and 1 Aficamten-focused trials) involving 463 patients were included in the meta-analysis. Compared to patients receiving placebo, the cardiac myosin inhibitor group demonstrated statistically significant differences in baseline percent change in mean resting LVOT gradient (MD -62.48, CI -65.44, -59.51, p <0.00001) and Valsalva LVOT gradient (MD -54.21, CI -66.05, -42.36, p <0.00001), as well as number of patients achieving NYHA Class Improvement ≥ 1 (OR 3.43, CI 1.90, 6.20, p <0.0001). Regarding secondary outcomes, the intervention group demonstrated statistically significant reductions in meant percent change from baseline in NT-proBNP (MD -69.41, CI-87.06, -51.75, p < 0.00001), Troponin I (MD, -44.19, CI -50.59, -37.78, p < 0.00001), and LVEF (MD -6.31, CI -10.35, -2.27, p = 0.002).

Conclusion:
The use of cardiac myosin inhibitors in patients with symptomatic hypertrophic cardiomyopathy may confer both clinical and sympatomatic benefits, at the possible expense of LV ejection fraction. Further trials with large sample sizes are needed to confirm our findings.
Abstract 15502: Exercise as a Risk Factor for Arrhythmic Mitral Valve Prolapse
Authors: Gamble Forrest N , Arps Kelly E , Pokorney Sean , Sun Albert
Published: June 2023

Background:
Mitral valve prolapse (MVP) is a common valvular abnormality found in approximately 2.4% of the population. Whereas most cases are benign, an increasingly recognized sequela of MVP is sudden cardiac death (SCD), but risk factors for SCD are not well-defined. Exercise has not been explored as a potential risk factor for SCD in MVP.

Hypothesis:
We tested the hypothesis that patients with MVP and SCD would be more likely to exercise or be competitive athletes than MVP controls with the capacity to exercise.
Methods -
The study population was generated from the Duke Epic EHR and determined by ICD-10 codes for MVP and SCD. A comparison group of patients with MVP with exercise data was used. Patients were included if they had guideline-based diagnosis of MVP on echocardiogram or cardiac magnetic resonance imaging. Exercise <1 hour per week was defined as being sedentary and time >1 hour per week or status as a competitive athletes were defined as habitual exercisers.

Results:
Of the 27 patients with MVP and SCD 18 had documentation of exercise time per week. There were 42 in the control group. Patients with SCD were younger [(54.8 +/-15.1) vs. (63.9 +/- 14.1) p= 0.03], and more likely to have bileaflet prolapse [13/18 (72%) vs. 15/42 (36%), p=0.01]. Patients with SCD were more likely to be habitual exercisers vs. sedentary [16/18 (89%) vs. 17/42 (40.5%), p = .025]. 20 patients with MVP and SCD had documentation of activity level at the time of event. 10 were exercising (50%), 5 (25%) working or doing housework, 4 (20%) resting and 1 (5%) sleeping.

Conclusion:
Exercise time >1 hour per week is associated with sudden cardiac death in Mitral Valve Prolapse. Exercise may be a trigger of SCD; however, more data is needed to better characterize exercise as a risk factor for SCD in this population.
Abstract 15504: High-Throughput Assessment of Molecular Mechanisms of Drug-Induced Arrhythmia Proclivities and Their Sex Dependence
Authors: Rouen Kyle C , Ngo Khoa , Kognole Abhishek , Dawson John , Emigh Aiyana , Bekker Slava , Yarov-Yarovoy Vladimir , MacKerell Alexander D , Vorobyov Igor
Published: June 2023

Introduction:
The hERG K
+
channel is responsible for the repolarizing cardiac current
I
Kr
. Drug block of hERG can prolong the QT interval on the surface electrocardiogram and in some cases promote deadly arrhythmias. Previous studies suggested that drugs that preferentially bind to the hERG channel’s inactivated state have higher proarrhythmic proclivities. Electrophysiology experiments and multiscale simulations also predicted that sex hormones can suppress hERG current and exacerbate drug-induced cardiotoxicity.

Hypothesis:
Atomistic simulations can make reliable correlations between a drug’s chemical structure and its state-dependent hERG binding affinities allowing us to distinguish safe from dangerous hERG blockers.

Methods:
We utilized site identification by ligand competitive saturation (SILCS), a pre-compute ensemble molecular docking technique, to predict hERG-channel binding poses and affinities of drug molecules. To improve agreement of SILCS results with experimental and molecular dynamics simulation data, we used a Bayesian machine learning protocol to optimize docking parameters.

Results:
We analyzed state-dependent binding of a sample set of 55 known hERG blockers and seven sex hormones to available structural models of the hERG channel. SILCS computed dissociation constants,

K
D

, show good correlation with experimental IC
50
values for our open-state model (Panel A) and predict drug and hormone binding sites in agreement with previous studies (Panel B) validating the methodology.

Conclusions:
Our computational methodology allows us to do high-throughput screening and differentiation of open vs. inactivated-state hERG channel drug binding and can also predict how hormones may modulate a drug’s hERG blocking activity. This provides more selective criteria for differentiating cardiac safe and dangerous drugs compared to using only hERG block and QT prolongation as surrogate markers of pro-arrhythmia risk.
Abstract 15510: Big Heart Problems: A Case of Reversible Nonischemic Cardiomyopathy Due to Severe Hypothyroidism
Authors: Minhas Simran , Malik Saleena , Albashash Hazem , Patel Karnik , Kern John
Published: June 2023

Introduction:
Cardiomyopathy is a heterogeneous group of myocardial diseases that can result in mechanical and electrical dysfunction. Thyroid insufficiency can increase the risk of cardiovascular abnormalities through multiple mechanisms including ventricular arrhythmias, hypertension, and heart failure.

Case Presentation:
Our patient is a 40-year-old Hispanic female with a past medical history of papillary thyroid carcinoma with a right-sided hemithyroidectomy in 2019 who presented to the emergency department with a 1-week history of dyspnea and peripheral edema. She has a family history of sudden cardiac death in her father. She discontinued her levothyroxine 75 mcg once daily dose 6 months ago as she believed this was causing her headaches. Her vital signs were significant for a heart rate of 117 beats per minute and a blood pressure of 185/147 mmHg. Her lab work showed a thyrotropin level of 94.6 uIU/mL, free thyroxine of 0.57 ng/dL, troponin T of 22 ng/L, and proBNP of 2660 pg/mL. A transthoracic echocardiogram (TTE) demonstrated global left ventricular hypokinesis with a left ventricular ejection fraction (LVEF) of 30-35%. Her electrocardiogram (EKG) showed normal sinus rhythm and corrected QTc of 494 ms. She received levothyroxine and furosemide and was discharged with guideline directed medical therapy (GDMT). Her outpatient TTE demonstrated improved LVEF of 40-45% after two months of levothyroxine use and GDMT.

Discussion:
Hypothyroidism has many cardiometabolic effects that directly impact cardiac function. Impairments in cardiac contractility can result in diastolic heart failure leading to low cardiac output, low heart rate, and low stroke volume. Increased vascular permeability results in protein-rich pericardial and pleural effusions. Myxedema, or non-pitting edema can be seen in long-standing, severe hypothyroidism. An increased QTc interval occurs due to prolonged cardiac action potentials which predispose the heart to ventricular irritability. Treatment with levothyroxine can improve cardiac output and contractility, however this carries increased risk of cardiac arrhythmias and myocardial ischemia.

Conclusion:
Severe hypothyroidism should be considered in cases of isolated nonischemic cardiomyopathy.
Abstract 15513: Angiovac as an Alternative to Surgical Excision of a Large Infective Endocarditis Vegetation
Authors: Ghawanmeh Malik , Hadadi Cyrus
Published: June 2023

Background:
Angiovac device is a suction cannula inserted percutaneously or surgically connected to extracorporeal circuit approved for removal of fresh soft thrombi/emboli. Cardiac surgery is indicated in Infective Endocarditis (IE) when the vegetation is >10 mm. Angiovac is used for IE in nonsurgical candidates. Here, we present 2 cases of successful use of Angiovac in treating large IE vegetation.

Presentation:
(1) A 70-year-old male with HFrEF and inducible VF on electrophysiological study requiring ICD implantation admitted for sepsis with Corynebacterium stratum bacteremia. TTE revealed mobile echo-density, 24 X 14 mm attached to the RV ICD lead. (2) 67-year-old female with sinus node dysfunction requiring permanent pacemaker who presented with constitutional symptoms. Blood culture grew coagulase-negative Staphylococcus. TEE revealed echodense coating around the RV lead, 15 mm in thickness.

Management:
Patient 1 was deemed nonsurgical candidate by cardiothoracic surgery. Instead, Angiovac was performed. Intraoperative TEE revealed a 30x20mm right atrial ICD lead vegetation. Angiovac catheter was advanced under TEE guidance to the right atrium. Once the catheter was abutting the infected thrombus multiple aspiration harvesting embolic material as in the picture. A postprocedural TTE demonstrated the absence of the RA echodensity. A subsequent laser lead extraction was performed. Patient 2 was given IV vancomycin. Angiovac procedure was successfully performed with subsequent laser lead extraction planning.

Conclusion:
AngioVac is a minimally invasive and effective procedure in the management of large vegetations in nonsurgical candidate patients.
Abstract 15528: Indeterminate Cardiomyopathy in a Patient With Birt Hogg Dubé Syndrome and a Clinical Diagnosis of Scleroderma and Prior Atrial Tachy Arrhythmias: A Diagnostic and Therapeutic Dilemma
Authors: Maher Aoife , McAdam Brendan F
Published: June 2023

Birt Hogg Dubé (BHD) syndrome, tachycardia induced cardiomyopathy and scleroderma are three well defined diagnoses. A link between them has not been reported. We present a diagnostic and treatment challenge, of a patient with BHD, clinical scleroderma and prior tachycardia induced cardiomyopathy with persistent left ventricular dysfunction despite restoration of sinus rhythm. Mr. X medical history includes recurrent bilateral pneumothoraces and bullectomy, with a cystic lung disease. He was diagnosed with BHD syndrome in 2018. He was diagnosed clinically with scleroderma with myositis based on symptoms and clinical signs with paucity of inflammation on muscle biopsy and negative biomarkers. There has been a limited response to immunosuppressants. In 2020 he presented with symptomatic paroxysmal atrial fibrillation. CMRI showed biventricular dilatation with increased volumes with LVEF of 40%, ​RVEF of 25% in sinus bradycardia. LGE showed subendocardial signal in ​​the basal and mid segment of the lateral and posterolateral walls with small foci of myocardial ​​​signal at the basal and mid inferior RV-LV hinge points.

A bespoke CRT-D (secondary to cavity size) was inserted following documented broad complex tachycardia, given the history of reduced ejection fraction despite medical therapy. Right and left heart catheterisations were normal. Endomyocardial biopsy showed no pathological features and no fibrosis or evidence of infiltrative disease. Genotype results are pending. BHD is a genetic disorder, affecting folliculin protein, associated with cystic lesions of the lung, kidney, and skin with an increased risk of renal cell carcinoma (1). There is no known link of BHD syndrome with cardiomyopathy. Studies have demonstrated folliculin has a role in cardiomyocyte generation (2). Given the cardiac biopsy result, not in keeping with scleroderma or tachycardia induced cardiomyopathy, he may have an independent cardiomyopathy, or a first case of cardiomyopathy secondary to BHD.

Our challenge continues to be optimising available therapies ensuring the best quality of life, whilst balancing the potential need for cardiac transplant with lifelong immunosuppressant therapy in a condition which has a seven-fold increased risk of renal cancer.
Abstract 15536: Surface Lin28a Expression Consistent With Cellular Stress Parallels Indicators Of Senescence
Authors: Broughton Kathleen M , Esquer Carolina , Echeagaray Oscar H , Firouzi Fareheh , Shain Grant , Ebeid David , Monsanto Megan M , Yaareb Dena , Golgolab Leila , Gude Natalie A , Sussman Mark A
Published: June 2023

Aims:
Declining cellular functional capacity resulting from stress or aging is a primary contributor to impairment of myocardial performance. Molecular pathway regulation of biological processes in cardiac interstitial cells (CICs) is pivotal in stress and aging responses. Altered localization of the RNA binding protein Lin28A has been reported in response to environmental stress, but the role of Lin28A in response to stress in CICs has not been explored. Surface Lin28A redistribution is indicative of oxidative stress response in CIC associated with aging and senescence.

Methods and Results:
Localization of Lin28A was assessed by multiple experimental analyses and treatment conditions and correlated to oxidative stress, senescence, and ploidy in adult murine CICs. Surface Lin28A expression is present on 5% of fresh CICs and maintained through passage 2, increasing to 21% in hyperoxic conditions but lowered to 14% in physiologic normoxia. Surface Lin28A is coincident with elevated senescence marker p16 and beta-galactosidase (β-gal) expression in CICs expanded in hyperoxia, and also increases with polyploidization and binucleation of CICs regardless of oxygen culture. Transcriptional profiling of CICs using single cell RNASeq reveals upregulation of pathways associated with oxidative stress in CICs exhibiting surface Lin28A. Induction of surface Lin28A by oxidative stress is blunted by treatment of cells with the antioxidant Trolox in a dose-dependent manner, with 300uM Trolox exposure maintaining characteristics of freshly isolated CICs possessing low expression of surface Lin28A and β-gal with predominantly diploid content.

Conclusion and Clinical Perspective:
Surface Lin28A is identified as novel surface marker of oxidative stress conditions that cause DNA damage and cellular senescence. Accumulation of surface Lin28A was inhibited by antioxidant treatment with lowered indices of cellular stress and senescence, revealing the potential of surface Lin28A as a diagnostic stress marker. Therapeutic strategies targeted toward surface Lin28 expression set the stage for next generation senolytics to remove stressed or senescent cells and promote recovery from tissue injury or aging.
Abstract 15543: Fibrin-Targeted Phase Shift Microbubbles Outperform Fibrin-Targeted Microbubbles for the Treatment of Microvascular Obstruction
Authors: Mohammed Soheb Anwar , Amjad Muhammad Wahab , Chen Xucai X , Acosta Maria Fernanda , Hanrahan Dillon , Unger Evan , MEUILLET Emmanuelle , Pacella John
Published: June 2023

Introduction:
Mortality from AMI has decreased in recent years; however, microvascular obstruction (MVO) occurs frequently, and is associated with rising post-AMI CHF, and has no definitive therapy. To address this urgent unmet need, we have developed an image-guided acute therapy, termed ‘sonoreperfusion’ (SRP), that resolves MVO via ultrasound-targeted microbubble cavitation (UTMC). We previously used standard-size, fibrin-targeted MBs and demonstrated enhanced reperfusion compared to standard-size, non-targeted MBs. However, phase shift microbubbles may allow greater clot penetration and perhaps more effective SRP, owing to their much smaller size Vs. standard MBs (~200 nm vs. 3 μm). Thus, we compared the SRP efficacies of fibrin-targeted phase shift microbubbles (FTPSMBs) (Microvascular Therapeutics, Inc), to standard-size fibrin-targeted microbubbles (FTMBs) for the treatment of MVO

Methods:
MVO of the rat hindlimb (
n=6
) was created by injecting porcine microthrombi into the left femoral artery under contrast-enhanced ultrasound (CEUS) guidance. DEFINITY
®
MBs (Lantheus Medical Imaging) were infused (2 mL/hr) through the right external jugular vein for CEUS. Following 10 min of stable MVO, a transducer was positioned vertically above the hindlimb to deliver therapeutic US pulses during concomitant administration of FTMBs/FTPSMBs (3 mL/hr). CEUS cine loops with burst replenishment were obtained at baseline (BL), 10 min post-MVO, and after each of the two SRP treatment sessions (TX1, TX2) and video intensities were analyzed (MATLAB_R2021a)

Results:
FTPSMBs treatment resulted in a greater increase in the blood volume (dB) and flow rate (dB/sec) than FTMB after each 10-minute treatment session (Figure 1)

Conclusions:
US-guided FTPSMB cavitation causes more rapid and complete reperfusion of MVO than FTMB, likely owing to their small size and more effective thrombus penetration. Studies to explore the underlying mechanisms are underway