bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18506: Echocardiographic Hemodynamic Assessment in Patients Undergoing Aortic Balloon Valvuloplasty: A Longitudinal Case Series
Authors: Karpenos Joseph E , Petrovic Marija , Arango Morales Juan , Elias Joseph , Hart Hannah , Shetty Samantha , Gupta Soumya , Choi James , Diaz Saravia Sara , Carter Kristen , Asogwa Nnedindu , Mdanat Eyadeh , kim Ga Hee , Leber Robert , Omar Alaa M , Argulian Edgar
Published: December 2023

Introduction:
We studied the anatomical and hemodynamic impact of balloon aortic valvuloplasty (BAV) using echocardiography in patients undergoing transcatheter aortic valve replacement (TAVR) or not.

Methods:
Retrospectively 22 patients referred for BAV were included [84±7 years, 63% women, ejection fraction (EF): 55±15%; EF≥50% in 16]. Echocardiography was done at 3 time points: baseline, immediately after BAV, and either after TAVR or during follow-up if TAVR was not performed.

Results:
BAV indications were: 2 urgent non-cardiac surgery, 7 cardiogenic shock, 1 for palliation, and 13 bridged to TAVR. At baseline, the aortic valve area (AVA) was 0.7±0.1 cm2, mean transaortic pressure gradient (PG) was 41±11 mmHg, stroke volume index (SVi) was 33±10 ml/m2, transvalvular flow rate (FR) was 197±44 ml/s, and transvalvular resistance (TVR) was 118±41 dyn.s.cm-5. Immediately after BAV, AVA significantly increased (0.9±0.2 cm2, p=0.002) and PG decreased (32±8.7 mmHg, p=0.019), indicating favorable anatomic outcomes. Interestingly, SVi (36±13, p=0.372), FR (209±60 ml/s, p=0.112), and TVR (95±49 dyn.s.cm-5, p=0.112) did not change immediately after BAV (Figure 1). During follow-up, TAVR patients exhibited near normalization of all valvular profiles, while non-TAVR did not show significant changes compared to post-BAV (Figure 1). After a median follow-up of 28 months, 7 patients died, 9 had cardiac hospitalizations, 2 had strokes, and 3 had acute coronary syndromes. As expected, TAVR had a significantly lower incidence of non-fatal composite outcomes compared to non-TAVR (1 vs. 9, p=0.007).

Conclusions:
Our findings indicate that BAV did not lead to substantial hemodynamic improvement in terms of transvalvular flow, flow rate, or valvular resistance, which appeared to improve only with TAVR. The modest anatomical effect of BAV did not seem to justify the high clinical risk associated with the procedure.
Abstract 18529: Early Coronary Revascularization Among "Stable" Patients With Non-ST-Segment Elevation Acute Coronary Syndromes: The Role of Diabetes and Age
Authors: Fabin Natalia , Cenko Edina , Vadalà Giuseppe , Mendieta Badimon Guiomar , Kedev Sasko , Kostov Jorgo , vavlukis Marija , Milicic Davor , Vasiljevic zorana , Zdravkovic Marija , Badimon Lina , Galassi Alfredo , Manfrini Olivia , Bugiardini Raffaele
Published: December 2023

Introduction:
Despite improvement in the management of patients with non-ST-elevation acute coronary (NSTE-ACS), this condition is still linked to a substantially increased mortality and morbidity among diabetic patients. Specifically, it remains uncertain whether patients whose condition can safely be stabilized at hospital admission should routinely receive an early coronary revascularisation.

Hypothesis:
We tested the hypothesis that a strategy of early coronary revascularization within 24 hours of diagnosis is superior to an initial conservative strategy in terms of clinical outcomes in diabetic patients who met stabilisation criteria at hospital admission. Comparison was made with a cohort of nondiabetic patients.

Methods:
The ISACS-TC database was queried for a sample of diabetic and nondiabetic patients with diagnosis of NSTE-ACS. Those with recurrent angina after hospital admission, cardiac arrest, haemodynamic instability, and serious ventricular arrhythmias were excluded. The characteristics between groups were adjusted using inverse probability of treatment weighting models. Co-primary end points were all cause 30-day mortality and the composite end point of all cause 30-day mortality and left ventricular (LV) systolic dysfunction. Risk ratios (RRs) with their 95% CIs were employed.

Results:
Of the 7,473 NSTE-ACS patients identified, 2,220 were diabetics. Early revascularization was associated with survival benefit only in the elderly (≥65 years) both in diabetics (3.7% vs 6.6%; RR: 0.56; 95% CI: 0.32-0.96) and nondiabetic patients (2.8% vs 5.1%: RR: 0.55; 95% CI: 0.34-0.87). In the elderly population, an initial conservative strategy increased the risk of death or LV systolic dysfunction by 15.2% in diabetics compared with nondiabetic patients (37.7% vs 32.7%; RR: 1.15; 95% CI: 1.02-1.30).

Conclusions:
Early coronary revascularization does not lead to any survival advantage within 30 days from admission in a large number of NSTE-ACS patients who present to hospital in stable conditions. An early invasive management strategy may be best reserved for the elderly either with or without diabetes. The benefit of this strategy appears to be more pronounced in the diabetic population.
Abstract 18546: Vasoactive Medication Variability in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock
Authors: Schenck Christopher , Banna Soumya , Chouairi Fouad , Heck Cory , Grammatico Megan , Kochar Ajar , Miao Jennifer , Ali Tariq , Jentzer Jacob C , Van Diepen Sean , Miller Elliott
Published: December 2023

Background:
Patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) often require vasoactive medications to maintain organ perfusion. However, there are limited data on the real-world use of vasoactive medications in this population.

Methods:
We used the Vizient® Clinical Data Base to identify patients aged ≥18 years who were admitted between 2015-2019 with AMI-CS and required mechanical ventilation. We report the proportion of patients receiving vasoactive medications by day as well as site-level variability for vasoactive medication strategies using the median odds ratio (MOR), which quantifies the odds that a patient receives a strategy at two randomly selected sites after adjusting for covariates.

Results:
We identified 10,758 patients from 160 centers admitted with AMI-CS. The median age was 65.8 years, 29.8% were female, 83.6% received vasoactive medications in the first 5 days, and 56.9% received temporary mechanical support. The most used vasoactive medication on day 1 was norepinephrine (48.2%), followed by epinephrine (31.5%), and dopamine (16.9%) (
Figure
). On day 1, 65.9% and 36.2% of patients receiving vasoactive medications were prescribed ≥2 or ≥3 different medications, respectively, including 111 different combinations. Among patients receiving inotropes (N=4,485), there was a nearly 3-fold difference in milrinone use across sites after accounting for differences in patient characteristics (MOR 2.89; 95% confidence interval [CI]: 2.39-3.38). For patients receiving either norepinephrine, dopamine, or epinephrine on day 1 (N=3,224), there was a nearly 2-fold difference in the use of norepinephrine as a first-line vasopressor across sites (MOR 1.84; 95% CI: 1.59-2.06).

Conclusion:
Norepinephrine is the most commonly used vasoactive medication in patients with AMI-CS. However, there is substantial site-level variability in vasoactive medication strategies, which require further study.
Abstract 18553: Different Leg Symptoms and the Presence of Peripheral Artery Disease in the Community: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Study
Authors: Ejiri Kentaro , Hua Simin , Qi Qibin , Williams-nguyen Jessica S , Garcia-Bedoya Olga , Daviglus Martha L , Sotres-Alvarez Daniela , Ballew Shoshana , Allison Matthew A , Kaplan Robert , Cordero Christina , Hurwitz Barry E , Matsushita Kunihiro
Published: December 2023

Introduction:
Intermittent claudication is manifestation of lower extremity peripheral artery disease (PAD). However, most patients with PAD either have atypical leg symptoms or no symptoms. To what extent leg symptoms are associated with the presence of PAD in the community is unknown.

Methods:
We studied 8,402 HCHS/SOL participants aged 45 and older (mean age 56.2 years, 54% female) without a clinical diagnosis of PAD. We categorized leg symptoms with walking into: (a) typical calf pain (calf pain on exertion relieved within 10 min after stopping); (b) atypical calf pain (same as (a) except no quick relief after 10 min); (c) non-calf pain (exertional leg pain but not in calf); and (d) leg pain at rest (ever pain during standing or sitting) based on a questionnaire. PAD was defined as an ankle-brachial index (ABI) ≤0.9. We first quantified the associations of leg symptoms with the presence of PAD using multivariable logistic regression. Then, we assessed the validity of different leg symptoms to identify PAD. All analyses accounted for survey weighting.

Results:
The prevalence of PAD was 4.8% (95% CI 4.1-6.0%). The prevalence of leg symptoms are displayed in Figure 1A (e.g., 1.9% for typical calf pain). In multivariable logistic models, only typical calf pain was significantly associated with PAD, and its adjusted OR exceeded 5 (5.52 [95% CI 2.60-11.7], Figure 1A). In terms of validity, typical calf pain had 98.5% specificity, but the sensitivity was ~10% (Figure 1B) and the positive predictive value was 24.1%. The c-statistic of this leg symptom classification for detecting PAD was 0.58.

Conclusions:
In Hispanics/Latinos without clinical history of PAD, only typical calf pain on exertion was robustly associated with the presence of PAD. However, the limited positive predictive value and discrimination indicate the need to optimize the target population and/or further refine leg symptoms to utilize them to detect PAD in the community.
Abstract 18555: Global Burden of Congenital Heart Disease and Its Trend From 1990-2019 in 38 OECD Countries: A Benchmarking Analysis for the Global Burden of Disease Study
Authors: Patel Hardik Y , RATHEESH RANI , Anum . , Thota Anjani Kumar , Rachapudi Shasank V , John Jobby , Koppana Viswaja , Hassan Khawaja Muthammir , DESAI HARDIK D
Published: December 2023

Introduction:
Congenital heart disease (CHD) is the 1st leading cause of deaths among all deaths associated with congenital birth defects in (Organization for Economic Cooperation and Development) OECD countries, constituting a significant health concern that imposes a substantial burden on healthcare systems and society.

Methods:
Using the Global Burden of Disease methodology, this study assesses the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) associated with CHD in 38 OECD countries by sex, year, and location, covering the period from 1990 to 2019. The results are presented in both all age counts and age standardized rates (ASR) per 100,000 person-years.

Results:
From 1990 to 2019, the total number of prevalent cases of CHD increased from 1,469,128 (95%UI: 1,292,909-1,671,743) to 1,590,654 (1,387,114-1,815,338). In contrast, CHD-related deaths decreased from 37,291 (31,629-47,869) in 1990 to 13,886 (10,668-16,919) in 2019. The annual percentage of change (APC) in age-standardized mortality (ASMR) decreased by 60%, while the ASIR showed almost no change but decreased by 3%. Notably, the highest APC in ASIR was observed in Czechia (27%), Sweden (21%), Hungary (18%), and the United States (11%), while Turkey (28%) and Canada (21%) had the lowest APC increases. The highest APC increase in ASIR among females was observed in France (29%)

Conclusions:
Despite a decrease in the burden of CHD over the last three decades, it remains a significant concern in OECD countries. The impact of CHD is felt by individuals, families, healthcare systems, and the economy, emphasizing the ongoing need for comprehensive strategies to address this burden.
Abstract 18565: Statin Utilization and Outcomes Among Patients With Coronary Artery Disease Undergoing Percutaneous or Surgical Revascularization
Authors: Mulukutla Saarang S , Zhu Jianhui , Thoma Floyd W , MARROQUIN Oscar C , Makani Amber , Sultan Ibrahim , Shapiro Michael D , Saeed Anum
Published: December 2023

Background:
Patients undergoing coronary revascularization are at high risk for adverse health outcomes. Accordingly, current guidelines suggest high-intensity use of statin intervention therapy to help mitigate atherosclerotic risk. We analyzed outcomes of patients following coronary revascularization stratified by the level of statin intervention in a large, real-world integrated healthcare system.

Methods:
Patients were stratified by type of coronary revascularization (percutaneous coronary intervention (PCI) vs coronary artery bypass grafting (CABG)). Statin use was divided as: (1) no statin, (2) less than guideline-directed statin intensity (<GDSI), and GDSI. HRs and incidence rate per 1000-person years were assessed for secondary ASCVD outcomes (MI, ischemic stroke/TIA and all-cause death) in the population.

Results:
Over a mean follow up of about 5 years, a total of 33,513 patients underwent PCI and 12,436 underwent CABG. Over 35% of patients in both groups received either <GDSI or no statin therapy. Patients who underwent PCI and were given no statin treatment had higher incidence of MI (69 vs 23 per 1000PY), stroke (21 vs 10) and death (69 vs 30) than those on GDSI. Patients who underwent CABG and were given no statin treatment had higher incidence of MI (31 vs 15 per 1000PY), stroke (30 vs 13) and death (79 vs 20) than those on GDSI. Amongst both groups, adjusted analysis showed that patients receiving GDSI had significantly lower risk for all major adverse cardiovascular outcomes (Table). In particular, GDSI in patients undergoing PCI was associated with the most significant reduction in MI, with an HR of 0.42.

Conclusions:
Underuse of GDSI was highly prevalent in patients undergoing coronary vascularization, both for PCI and CABG, and this was associated with suboptimal outcomes. Further practical interventions should be studied to assure that patients are treated aggressively with guideline directed therapies to lower risk for adverse outcomes.
Abstract 18583: Preclinical Efficacy and Safety of Intravenously Administered LX2020 Gene Therapy for the Treatment of Arrhythmogenic Cardiomyopathy
Authors: Sheikh Farah , Zhang Jing , Gutierrez Lara Erika , Do Aryanne , Nguyen Lena , Bradford William H , Nair Anju , Selvan Nithya , Gutierrez Sonia , Law Ken , Fenn Tim , Khanna Richie
Published: December 2023

Introduction:
Arrhythmogenic cardiomyopathy (ACM) is a rare, incurable inherited cardiac disease resulting in mortality through sudden death and heart failure. ACM cases are linked to mutations in desmosomal genes, with the most frequent related to plakophilin-2 (PKP2), resulting in haploinsufficiency. LX2020 is an adeno-associated viral (AAV) based gene therapy intended to restore human PKP2 (hPKP2) protein expression. However, its efficacy in disease settings and safety has not been established.

Hypothesis:
LX2020 mediated hPKP2 expression is sufficient to scaffold the desmosomal complex to prevent cardiomyocyte loss and circumvent structural damage to improve cardiac electrical and mechanical function as well as promote survival, while being safe and well tolerated.

Methods:
LX2020 was intravenously administered to PKP2 mutant mice with severe ACM and non-human primates (NHPs) at various doses and was evaluated 12 weeks post-dose for efficacy and safety, respectively. Endpoints in mice involved effect of LX2020 on various cardiac disease-relevant phenotypes and survival, while safety, tolerability, biodistribution and expression was assessed in NHPs.

Results:
In ACM disease settings, LX2020 showed dose-dependent increase in hPKP2 expression that was sufficient to restore desmosomal proteins and cell-cell junctional complexes inhibiting further cardiac structural damage resulting in improved electrical and mechanical dysfunction, ultimately leading to improved survival. In NHPs, LX2020 showed dose-dependent biodistribution in various organs including the heart, with increases in cardiac hPKP2 mRNA and protein expression that were safe and well tolerated. Notably, LX2020 showed cardiac hPKP2 expression in mice and NHPs, which reached above or close to healthy human PKP2 protein levels, respectively, indicating that LX2020 could lead to therapeutic levels of PKP2 expression.

Conclusions:
Collectively, these data support the efficacy of LX2020 in restoring cardiac hPKP2 expression and rescuing the progressively advancing severe ACM diseae, while being safe and well tolerated. LX2020 offers a promising gene therapy that provides maximal therapeutic benefit with minimal safety risk for PKP2-ACM populations.
Abstract 18589: Disparities in Low Cognitive Function Score and Mortality Risk Among Older Adults in the United States
Authors: Lu Yuan , Tian Wenya , Li Xumin , Wu Yinfei , Liu Yuntian , Chen Kai , Zang Emma , Herrin Jeph , Krumholz Harlan M
Published: December 2023

Introduction:
Low cognitive function predicts mortality in older adults. This study examined cognitive assessment disparities by age, sex, and race, and the association of low cognitive function with mortality.

Methods:
We analyzed data from the National Health and Nutrition Examination Survey (2011-2014) with linked mortality. Cognitive function was measured by the Digit Symbol Substitution Test (DSST), Consortium to Establish a Registry for Alzheimer's disease Word Test (CERAD), and Animal Fluency Test (AFT). Low cognitive function was defined as scoring below the 25th percentile. Cox regression models was used to assess the association with mortality.

Results:
The study included 3014 adults aged 60 or older (mean age: 69.7 years; 54.9% women; 9.2% Black, and 78.8% White). A total of 1192 participants had low cognitive function. Older age (70+), female sex, and Black race were associated with lower DSST scores by 11.7 (13.1-10.4) points, 3.4 (2.2-4.6) points, 14.7 (17.2- 12.1) points, respectively, compared with younger age (60-70), male, and White individuals. Low cognitive function was significantly associated with all-cause mortality (HR= 2.04, 95% CI: 1.47-2.81) and cardiovascular mortality (HR= 1.88, 95% CI: 1.41-2.50) after adjusting for age, sex, race/ethnicity, education, income, employment status, physical activity, and smoking. These associations were consistent across all measures of cognitive function. There were no significant interactions in HRs for mortality by age, sex, and race.

Conclusions:
In a community-based sample, cognitive dysfunction can double the risk of mortality. Whether this represents a marker or a mediator remains to be determined.
Abstract 18615: Utilizing Deep Learning Network for Analyzing National Health and Nutrition Examination Survey Data: Investigating the Association Between Self-Reported Sleep Duration and Hypertension
Authors: Chung Dr Debbie , Rogers April , Seixas Azizi A , Zizi Ferdinand , Jean Louis Girardin
Published: December 2023

Introduction:
Epidemiological evidence consistently demonstrates significant links between self-reported sleep duration and hypertension (HTN). However, traditional logistic regression models may not capture the full complexity of these associations. Therefore, in this study, we employed a Deep Learning Network to model the intricate relationships between sleep duration and HTN.

Methods:
Data were extracted from participants (n=38,540) in the National Health and Nutrition Examination Survey (2006-2016), a nationally representative study of the US civilian non-institutionalized population. Self-reported demographic, medical history and sleep duration were determined from household interview questions. HTN was determined as SBP ≥ 130 mmHg and DBP ≥ 80mmHg. We used a deep neural network architecture with three hidden layers with two input features and one binary output to model associations of sleep duration with HTN. The input features are the hours of sleep (limited to between 4 and 10 hours) and its square; and the output variable HTN. Probability predictions were generated 100 times from resampled (with replacement) data and averaged.

Results:
Participants ranged from 18 to 85 years old; 51% Female, 41% white, 22% black, 26% Hispanic, 46% married, and 25% <high school. The model showed that sleeping 7 hours habitually was associated with the least observed HTN probabilities (P=0.023%). HTN probabilities increased as sleep duration decreased (6hrs=0.05%; 5hrs=0.110%; 4hrs=0.16%); HTN probabilities for long sleepers were: (8hrs=0.027; 9hrs=0.024; 10hrs=0.022). Whites showed sleeping 7hrs or 9hrs was associated with lowest HTN probabilities (0.008 vs. 0.005); blacks showed the lowest HTN probabilities associated with sleeping 8hrs (0.07), and Hispanics showed the lowest HTN probabilities sleeping 7hrs (0.04).

Conclusions:
We found that sleeping 7 hours habitually confers the least amount of risk for HTN. Probability of HTN varies as a function of individual’s sex and race/ethnicity. Likewise, the finding that blacks experience the lowest HTN probability when they sleep habitually 8 hours is of great public health importance.

Support: R01HL142066, R01AG067523, R01AG075007
Abstract 18616: When Stress Strikes the Heart: Developing Takotsubo Cardiomyopathy With Uncommon Complications
Authors: Pujar Sanjay , Ramaswamy Geetha , Pandey Mandvi , Rincon Enrique
Published: December 2023

Introduction:
Takotsubo cardiomyopathy (TCM), also known as stress-induced cardiomyopathy or "broken heart syndrome," is a rare condition that predominantly affects postmenopausal women. The etiology of TCM is not entirely understood, but it is thought to be related to catecholamine-induced myocardial stunning. Clinical presentation typically mimics acute coronary syndrome. Left ventricular outflow tract obstruction (LVOTO) is an uncommon complication of TCM, with only a few cases reported in the literature.

Case Presentation:
A 78-year-old lady presented with chest pain that started a week ago. It was associated with exertion and resolved with rest. It was located substernally, pressure-like, and was 7/10 in intensity. EKG revealed diffuse inferolateral ST segment depression. Her initial troponin was 0.2 which climbed up to 5. She was diagnosed with NSTEMI and was started on IV heparin. Cardiac catheterization revealed no significant CAD. Echocardiography revealed wall motion abnormalities suggestive of Takutsubo Cardiomyopathy (apical ballooning syndrome) with apical hypokinesis and hypercontractile basal segment of the left ventricle. She also had LVOTO with a peak and mean gradient of 80 and 48 mmHg respectively. Her LVEF was calculated to be 40 %. There also was accompanied systolic anterior motion of the mitral valve leaflet. Given the above findings, she was started on a beta blocker along with an angiotensin receptor blocker. Patient’s chest pain resolved with this and was discharged in a stable condition on day three. Follow up appointment at the clinic showed complete resolution of her HOCM and LVOTO.

Discussion:
The key to managing patients with TCM is to identify LVOTO early, and avoid inotropes and vasodilators. Beta blockers are seen as the cornerstone of treatment. Fortunately, this is a self-resolving condition and the prognosis is excellent with resolution of echocardiographic abnormalities and symptoms within a few weeks’ time.
Abstract 18634: Quantification of Coronary Volume to Left Ventricular Mass Ratio Using CT Angiography
Authors: Hadjiabdolhamid Negin , Duong Lynn , Molloi Sabee
Published: December 2023

Introduction:
Coronary volume to left ventricular mass ratio (V/M) is a promising parameter that can detect physiological imbalances between coronary vasculature and the supplied myocardium. However, the existing method that assesses the V/M using epicardial vascular volume based on coronary CT angiography (CCTA) is labor intensive and prone to variability due to its dependence on coronary vasculature visualization.

Hypothesis:
A new technique based on CCTA and its associated bolus tracking data enables an efficient semi-automated approach that can reproducibly measure the V/M with less variability compared to the existing manual approach.

Methods:
The V/M was assessed by both existing manual and the new semi-automated techniques in 6 Yorkshire swine (49.1 ± 9.0 kg). Using a 320-slice CT scanner, 9 pairs of repeated CT measurements were made (100 kVp; 200 mA) with a 5-minute delay between each acquisition. Contrast (0.5 mL/kg; 370 mgI/mL) and a diluted contrast/saline chaser (0.5 mL/kg; 30:70contrast/saline) were injected peripherally at 5mL/s. Bolus tracking and triggering were followed by a single scan acquired at the peak of the aortic enhancement. Using a first-pass analysis model, the bolus tracking and single volume scan data were used to derive the total vascular blood volume (mL). Standard myocardial segmentation was used for myocardial mass (g) measurement. The V/M was also calculated from CCTA using the manual technique, by segmenting coronary luminal volume and myocardial mass. The reproducibility of the V/M was assessed using regression analysis. The variability of the two techniques for determining normal V/M was quantified using the coefficient of variation.

Results:
The first ((V/M)
1
) and second ((V/M)
2
) measurements were related by (V/M)
2
= 1.039 (V/M)
1
+ 0.002 (Pearson’s r = 0.90; RMSE = 0.01 mL/g). The coefficient of variation was 0.13 and 0.24 for the V/M calculated from the new semi-automated and existing manual techniques, respectively.

Conclusion:
A novel semi-automated technique can be used for quantification of V/M with low variability. This technique can potentially be used for early detection of physiological imbalances between coronary vasculature and the supplied myocardium following coronary artery disease.
Abstract 18637: Lower α-Klotho is Associated With Vulnerable Coronary Artery Plaque Characteristics
Authors: Akhiyat Nadia , Ozcan Ilke , Lerman Lilach O , Lerman Amir
Published: December 2023

Introduction:
α-Klotho (klotho) is a geroprotective protein inversely associated with coronary artery disease CAD and vascular aging. This study used intravascular ultrasound (IVUS) to study coronary artery plaque characteristics of patients with low circulating klotho.

Hypothesis:
Lower klotho is associated with vulnerable coronary artery plaque characteristics.

Methods:
Patients undergoing coronary angiogram for chest pain who had no CAD (<40% stenosis) underwent IVUS assessment. Images were obtained from the mid-LAD to the coronary ostium. Stored arterial plasma was used for α-klotho analysis by enzyme-linked immunosorbent assay.

Results:
A total of 58 consecutive patients were retrospectively studied. The median circulating klotho level of the cohort was 0.27 ng/mL [0.15; 1.24]. Patients with klotho less than the median were compared to those with levels greater than or equal to the median and were similar in age (53 ±11 vs. 56 ±10, p = 0.235) and sex distribution (86% vs. 76% female, p = 0.324). Patients with less klotho had higher coronary plaque burden (21.42% [17.185, 31.955]
vs.
18.32 [10.5, 24.515], p=0.041) and larger plaque area (2.71 [2.03, 4.605]
vs
. 2.27 [1.41, 3.31] mm
3
/mm, p=0.058) compared to those with higher klotho. Lower klotho was associated with vulnerable plaque characteristics, including greater percentages of dense calcium (1.33% [0.265, 5.38]
vs.
0.43% [0.015, 1.73], p=0.037) and necrotic core (5.43% [2.245, 10.5]
vs.
2.22% [0.86, 4.50], p=0.011).

Conclusions:
Lower circulating klotho was associated with higher coronary plaque burden and vulnerable plaque characteristics. Klotho may be an early biomarker for risk in coronary artery disease.
Abstract 18669: Pheochromocytoma Crisis Precipitated by Carvedilol
Authors: Walder Zachary , Stefanelli Michelle , Vojnika Jetmir
Published: December 2023

Description of case:
Pheochromocytomas are rare, catecholamine-secreting tumors of the adrenal gland. Definitive treatment is surgical, but requires pre-operative optimization with alpha, followed by beta blockade (BB). Initial treatment with BB can precipitate pheochromocytoma crisis, characterized by hemodynamic instability and end-organ dysfunction. This case describes pheochromocytoma crisis in a young, healthy female after switching from metoprolol to carvedilol. A 27-year-old woman is evaluated by an outpatient cardiologist for recurrent palpitations, “hot flashes” and headaches. Mobile telemetry monitor reveals episodes of “SVT” for which she is started on metoprolol succinate. Given her symptoms, testing for plasma free metanephrines is ordered and is markedly abnormal. Subsequently the patient is switched from metoprolol to carvedilol. Within a few hours of taking carvedilol the patient reports sudden onset dyspnea, nausea, vomiting and chest pain. On arrival, vital signs are remarkable for a resting pulse of 130 and blood pressure of 130/97. EKG shows sinus tachycardia. Labs reveal a high-sensitivity troponin of 1,816 ng/L and a 2-hour troponin of 4,560. CT shows a 5.8 cm left adrenal mass. An echocardiogram reveals a reduced LVEF of 45-50% and is suggestive of reverse takotsubo cardiomyopathy. Her carvedilol is discontinued, she is started on prazosin and her symptoms resolve within 24 hours. She later resumes metoprolol and proceeds with surgical excision.

Discussion:
This case reports a pheochromocytoma crisis likely precipitated by carvedilol and complicated by reverse-takotsubo cardiomyopathy. Interestingly, the patient tolerated metoprolol despite being in the same class. This switch was made knowing she tolerated BB and with the idea that she would benefit from additional alpha-blockade. Carvedilol is a racemic mixture, with S-carvedilol binding beta-1 and -2 receptors while R-carvedilol binds strictly alpha-1. There is evidence that patients catabolize the enantiomers differentially, resulting in higher concentrations of one enantiomer in an unpredictable manner. It is therefore preferred to avoid all BB before sustained alpha blockade while treating pheochromocytoma despite the patient’s previous tolerance.
Abstract 18672: Impact of Enhanced Artificial Intelligence on Clinic Burden From False Alerts of Insertable Cardiac Monitors
Authors: Singh Jagmeet , Radtke Andrew , Rosemas Sarah , Ousdigian Kevin T
Published: December 2023

Background:
AccuRhythm AI is a suite of cloud-based classification algorithms that filter and suppress false pause alerts and atrial fibrillation (AF) episodes transmitted by insertable cardiac monitors (ICMs). An enhancement to the AF algorithm (AI v2) reduces false AF alerts by 50% relative to the original AI (AI v1) but the impact of this improvement on clinic experience is unknown.

Aim:
Determine the projected annual impact of AI v2 on Pause and AF alerts in a real-world patient population.

Methods:
Real-world data were obtained from de-identified LINQ II ICM patients with ≥3 months of follow-up. Previously published performance of each AI algorithm broken out by patient reason for monitor were projected onto the data. Results were extrapolated to the average 200-ICM clinic. The study endpoints were true alert retention, false alert suppression, and clinic review burden reduction.

Results:
The dataset consisted of 16,301 ICMs with mean follow-up of 7 months. Reasons for monitor were Known AF (25%), Suspected AF / Cryptogenic Stroke (40%), Syncope (23%), and Other (12%). The mean number of alerts per patient-year was 17.9 AF and 4.3 Pause. Projection of AI v2 resulted in minimal loss (0.9%) of true AF and Pause alerts, annually, with no loss in Pause and 1.0% in AF. AI v2 reduced annualized false AF and Pause alerts by 91% (97.4% false Pause and 88.1% false AF reduction) relative to the ICM and 35% relative to AI v1. This translates to 401 and 22 annual review hours saved for a 200-ICM clinic, respectively.

Conclusion:
The AF enhancement provides a meaningful reduction to the average ICM clinic’s review burden by eliminating most false Pause and AF alerts while maintaining nearly all true alerts.
Abstract 18676: Aneurysmectomy or No Aneurysmectomy - An Unknown Heart Failure Terrain
Authors: Penmetsa Mouna , Badr Mai , Nadig Vidya , Vlismas Peter , Scatola Andrew
Published: December 2023

Case Report:
A 40-year male with a history of traumatic inferoapical ventricular septal rupture after a motor vehicle accident status post patch repair and left ventricular thrombus on Rivaroxaban presented to the ED with hemoptysis. The patient on arrival was hemodynamically stable. CTA revealed a new 6.9 cm left ventricular pseudoaneurysm and an echocardiogram revealed an EF of 30% with a pseudoaneurysm involving the entire distal septum, lateral wall, and apex and a ventricular septal rupture into the intraventricular septum. Cardiac MRI revealed a pseudoaneurysm from the inferoseptal wall measuring 9.6 x 6.9 x 10.0 cm and a stroke volume of 123 mL. A right heart catheterization revealed no evidence of left-to-right shunting. Given heart failure with reduced ejection fraction in the setting of a pseudoaneurysm and the complexity of aneurysm repair, advanced heart failure and cardiothoracic surgery teams were consulted for conventional surgical and transplant evaluation. Due to social barriers, the patient was declined from transplant and ultimately proceeded with patch repair. Intraoperative echocardiography revealed a post-operative EF of 25%.

Discussion:
This case highlights the need for further data on pseudoaneurysms that are confounded with concurrent heart failure. For this patient, the concerns were for adequate stroke volume given the extent of the pseudoaneurysm and whether improvement in systolic function could be seen with repair or result in further decline. It was postulated that surgical repair would raise his effective stroke volume, and thus improve cardiac function. Postoperative EF changes could have been further explained by myocardial stunning during anesthesia or rapid changes in end-diastolic volume with aneurysmectomy altering Frank-Starling hemodynamics. With isolated case report data, further aneurysmectomy outcome characterization is thus imperative to guide advanced heart failure treatment and improve patient mortality.
Abstract 18691: Asporin Attenuates Pulmonary Arterial Smooth Muscle Cell Proliferation and Regulates Pulmonary Hypertension Development
Authors: Medzikovic Lejla , Sun Wasila , Ruffenach Gregoire , HONG JASON , Eghbali Mansoureh
Published: December 2023

Introduction:
Pulmonary arterial hypertension (PAH) is a devastating pulmonary vascular lung disease characterized by increased pressure in the pulmonary arteries (PA) leading to cardiac right ventricular (RV) hypertrophy, RV failure, and ultimately death. Current PAH therapies merely improve symptoms temporarily and patients often need lung and heart transplantation. There is dire need for new insights into PAH pathophysiology to find novel therapeutic approaches. A key mechanism driving PAH is medial hyperplasia resulting from enhanced pulmonary arterial smooth muscle cell (PASMC) proliferation.

Methods:
We employed an unbiased bioinformatics approach in online-available microarray expression and single-cell sequencing datasets of dissected PA from PAH patients. In vitro experiments were performed in PASMC isolated from a female donor and PAH patient. Human lung tissue sections were obtained from the Pulmonary Hypertension Breakthrough Initiative Biobank. The Sugen/Hypoxia model was used to induce PH in rats.

Results:
We discovered that a novel gene, small leucine-rich proteoglycan Asporin (Aspn), is highly and significantly upregulated in PAH compared to donor PA and is most highly expressed in PASMC. We validated higher Aspn mRNA expression in human lungs and PASMC from PAH patients compared to controls, supporting our bioinformatics approach. Moreover, Aspn protein expression is elevated in PASMC in lung tissue sections from PAH patients compared to donors, as well as in PAH patient plasma
.
Functionally, silencing Aspn in PASMC from PAH patients promoted proliferation, whereas recombinant Aspn exerted opposite effects. To find potential downstream mediators of Aspn, STRING database analysis revealed that Aspn binds to the pro-proliferative mediator TGFβ1. Accordingly, TGFβ1 downstream mediator p-SMAD2/3 is enhanced upon Aspn silencing in PASMC. Intratracheal delivery of Aspn siRNA in rats aggravated Sugen/Hypoxia-induced PH, as assessed by RVSP, echocardiography and vascular remodeling.

Conclusions:
We hypothesize that elevated Aspn expression in PAH is a compensatory mechanism that inhibits PASMC proliferation, leading to decreased PA vascular remodeling, and that Aspn may be a novel therapeutic target against PAH.
Abstract 18732: Investigating the Impact of Weather Conditions on Out-of-Hospital Cardiac Arrest Occurrences in Hungary
Authors: Pal-Jakab Adam , Sipos Bence , Boldizsar Kiss , Nagy Bettina , Papai Gyorgy , Csato Gabor , Boussoussou Nora , Lovas Gabor , Szilagyi Brigitta , Sotonyi Peter , Zima Endre
Published: December 2023

Introduction:
The growing recognition of environmental factors that play a crucial role in the incidence of Out-of-hospital cardiac arrests (OHCA) has been reflected in various research studies.

Hypothesis:
Our goal was to explore the links between various weather conditions and the frequency of OHCA in Hungary from November 1, 2018, to April 25, 2022.

Methods:
We conducted a comprehensive analysis using data from the Hungarian National Ambulance Service and weather records. T-tests were employed for normal distributions, and Mann-Whitney tests were used in other instances. A significance level of 0.05 was applied in both cases.

Results:
We observed a noticeable rise in OHCA incidents during periods of extreme cold (average daily temperature (T) below 0 °C) and extreme heat (average daily T over 25 °C). Instances of OHCAs were significantly higher on days with rapid T changes (intraday T shift above 5 °C), with a p-value of 0.013. The frequency of OHCA cases also saw a notable increase on frontal days compared to non-frontal days. However, we found no significant correlation between precipitation and OHCA cases.

Conclusions:
In conclusion, our analysis found significant associations between extreme cold and heat, and rapid T changes with the incidence of OHCA, while frontal days and precipitation did not reach statistical significance.

Climate Change National Laboratory RRF-2.3.1-21-2021
Abstract 18762: Pacemaker Pocket Erosion - An Undesired Complication of Leuprolide Therapy
Authors: Al-Seykal Ibragim , Sherif Akil A , Mishra Ajay K , Bhat Ashwini , Sharma Nitish , Harizi Robert , Pacifico Luigi
Published: December 2023

Introduction:
Pacemaker pocket erosion is an uncommon delayed complication of the cardiac implantable electronic device (CIED) implantation that most frequently occurs in frail and elderly patients. We present a case of such a patient who developed pacemaker pocket erosion after being initiated on hormonal therapy for advanced prostate cancer.

Case presentation:
The patient is a ninety-three-year-old male with a history of persistent atrial fibrillation and dual chamber pacemaker in situ with last generator change two years prior presented with a two-week history of pacemaker wound dehiscence and exposed pacemaker. Six months earlier, the patient was diagnosed with advanced prostate cancer, was initiated on gonadotropin-releasing hormone agonist, leuprolide, and subsequently developed unintentional weight loss of 30 pounds. For two months prior to the current presentation, the patient noticed subjective discomfort at the site of the pacemaker pocket which he did not report to his cardiologist and eventually developed an erosive wound overlying the pacemaker pocket exposing the device (Image 1). He was admitted to the hospital and found to be hemodynamically stable, without leukocytosis and, negative blood cultures. Transthoracic and transesophageal echocardiograms showed no evidence of vegetation. He was empirically treated with daptomycin and was referred for pacing system extraction. He underwent pacing system replacement with leads and device extraction followed by leadless Micra VR (Medtronic, Minneapolis, MN) pacemaker implantation. Following a 4-week antibiotic course post pacemaker system extraction, the pacemaker pocket wound was fully healed.

Conclusions:
Aging and weight loss are known major risk factors for device-pocket erosion and externalization of the CIED. It highlights the importance of improving awareness of this entity and that initiation of hormonal therapy can be a contributing factor to such complications.
Abstract 18772: Transient Receptor Potential Cation Channel 6 (TRPC6) Deficiency Preserves Cardiac Mitochondrial Respiration and Attenuates Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction
Authors: Wang Zhen , Li Xuan , Docarmo Jussara M , Da Alexandre A , Omoto Ana C , Mouton Alan J , Hall John E
Published: December 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by diastolic dysfunction, cardiac hypertrophy and mitochondrial (MT) dysfunction. TRPC6, a non-selective cation channel that mediates Ca
2+
influx, is expressed in the heart and has been suggested to regulate MT function and participate in pathological cardiac hypertrophy. However, the role of excessive TRPC6 activation in HFpEF is unclear.

Hypothesis:
We hypothesized that TRPC6 deficiency would attenuate generation of MT-derived reactive oxygen species (ROS), MT dysfunction, and cardiac dysfunction in a model of HFpEF.

Methods:
HFpEF was induced in TRPC6 knock out (KO) and wild-type (WT) control mice via a combination of high-fat diet (45% fat) and L-NAME (0.5 g/L in drinking water) administration for 10 consecutive weeks. Cardiac function was assessed using echocardiography under normal conditions and after dobutamine (DOB)-induced stress (0.75 μg/g i.p). At the end of the study, MT oxygen consumption rate and MT-ROS generation were examined in isolated cardiac fibers using OROBOROS respirometry.

Results:
After 10 weeks of HFD+L-NAME, WT mice developed diastolic dysfunction and cardiac hypertrophy, whereas TRPC6 KO mice exhibited preserved diastolic function (IVRT: 21.5±1.1 vs 16.3±1.2 msec and E/E’: -35±2 vs -31±2 in WT and TRPC6 KO,
P
<0.05). During DOB stress test (10 mins after DOB injection), TRPC6 KO mice had greater increases in stroke volume (3.3±2.8 vs -2.7±2.0 μl,
P
<0.05) and fractional shortening (10.4±2.8 vs 2.4±3.1%,
P
<0.05) from baseline compared to WT mice. TRPC6 KO mice treated with HFD+L-NAME also exhibited higher MT oxygen consumption (136.7± 31.1 vs 101.1± 20.1 pmol/min/mg,
P
<0.05) and lower MT-ROS generation (0.43±0.3 vs 1.46±0.5 pmol/min/mg,
P
<0.05) compared to WT mice treated with HFD+L-NAME.

Conclusions:
This study demonstrates that TRPC6 deficiency attenuated diastolic dysfunction while preserving cardiac reserve capacity, improving MT respiration, and reducing MT-ROS generation in HFpEF induced by HFD+L-NAME. Targeting TRPC6 and its downstream signaling pathways may offer a promising therapeutic approach for future HFpEF treatments.
Abstract 18781: Targeting GPR39 in Pericytes for Preventing No Reflow After Acute Myocardial Infarction
Authors: Methner Carmen , Le Dai-Trang E , Kaul Sanjiv
Published: December 2023

Background:
No reflow (NR) continues to contribute towards morbidity and mortality in acute myocardial infarction (AMI). Currently, there is no treatment specific to NR. We demonstrated that NR is caused by pericyte-inducted capillary constriction and identified the G-protein coupled receptor, GPR39, through which the vasoconstrictor 15-Hydroxyeicosatetraenoic acid (15-HETE) results in pericyte contraction during myocardial ischemia. GPR39 knockout mice demonstrate a marked reduction in NR after AMI associated with less pericyte-induced capillary constriction. Consequently, we developed a drug candidate, VC108, that inhibits GPR39 with high specificity (antagonist potency, fpki=7.9) and no effect on 87 other receptors involved in cardiovascular regulation.

Methods:
Forty-nine Wild-type Sprague Dawley rats (3-4 weeks old) of both sexes underwent 1 hour of coronary occlusion followed by 1 hr of reperfusion. Either vehicle (n=13) or VC108 (in-vivo half-life of 2 hr) at 3 different doses: 0.3 (n=11), 0.5 (n=13), and 1.0 mg/kg (n-12) was injected 5 min before reperfusion. Risk volume (as %of LV volume) was derived from 4-6 short axis slices using Evans Blue staining and NR volume was measured using Thioflavin S.

Results:
There was no significant difference in the risk volume in animals treated with vehicle and the 3 doses of VC108 (Figure 1). In contradistinction, compared to vehicle, VC108 showed marked reduction in NR at all doses (Figure 2) with a trend towards lower NR volume at the highest dose.

Conclusion:
Pharmacological inhibition of GPR39 results in marked reduced in NR after AMI. These findings open up a novel approach to treating AMI.
Abstract 18799:
Edn1
is a Disease-Specific Marker in Endothelial Cells During Atherosclerosis
Authors: Dy Danielle
Published: December 2023

Introduction:
Coronary artery disease (CAD) is the leading cause of mortality in the United States. Multiple cell types contribute to the atherosclerotic plaques causing CAD, influencing its growth and propensity to rupture. Endothelial-to-mesenchymal transition (EndMT), the process by which endothelial cells (ECs) acquire characteristics of mesenchymal cells and loose canonical endothelial features, is correlated with an unstable plaque phenotype, although this transition remains poorly characterized.

Hypothesis:
A specific population of ECs may undergo EndMT, potentially contributing to the progression of atherosclerosis.

Methods:
We induced endothelial-specific lineage-tracing in

Tg
Cdh5-CreERT2

,

ApoE
-/-

mice, followed by 16 weeks of high-fat diet (HFD) to produce atherosclerosis. Aortic roots were collected from male and female disease-condition animals (n=13) and a baseline cohort that was not fed HFD (n=6). Single cell RNA sequencing was performed and analyzed using the Seurat package. RNAscope staining of transverse sections (n=10 per genotype per sex) was performed to characterize the lesion.

Results:
We identified multiple endothelial subtypes within the aortic root. One population, characterized by the marker Klk10, appears to give rise to a disease-specific population characterized by expression of
Edn1.
Upstream regulator analysis of differentially expressed genes between
Edn1+
and
Klk10+
populations predict this EC transition to be driven by EndMT-associated transcription regulators including SNAI2, TWIST2, STAT3, SNAI1, YAP1, and TEAD2. This analysis also predicted upregulation of pulmonary fibrosis idiopathic signaling, wound healing signaling, pathogen induced cytokine storm signaling, and hepatic fibrosis signaling pathways. This EndMT process, characterized by a single, linear trajectory, was the only disease-associated EC transition state identified in the atherosclerotic aortic root.

Conclusions:
We identified ECs undergoing EndMT in a mouse model of atherosclerosis and determined that this transition is the primary EC cell state transition during disease. We localized this process in situ in the atherosclerotic lesion and identified potential key transcriptional drivers of this process.