bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11358: Total Cost of Care in Heart Failure Patients Receiving Parenteral Iron Therapy for Iron Deficiency Anemia: A Retrospective Analysis
Authors: Kwong W J , Wang Kevin , Boccia Ralph V
Published: June 2023

Introduction:
Iron deficiency (ID) is a common comorbidity in heart failure (HF) patients. This study compared healthcare costs between treatment with ferric carboxymaltose (FCM) and low dose IV iron (LDI) in HF patients with iron deficiency anemia (IDA).

Methods:
Medical and pharmacy claims from IQVIA PharMetrics
®
Plus data were analyzed. Adult patients who received FCM or LDI (i.e iron sucrose, iron dextran, sodium ferric gluconate complex in sucrose) from 2017 to 2019, who had HF and IDA medical claims and were continuously eligible 6 months before (baseline) and 12 months after first (index) IV iron infusion were included. Patients with chronic kidney disease who required dialysis were excluded. Eligible FCM patients were required to receive 2 FCM doses within 21 days of index date. Healthcare resource use and costs for pre- and post-index periods were summarized descriptively. Post-index monthly inpatient, outpatient (excluding IV iron), and total costs for FCM and LDI were compared using generalized linear model with gamma log-link adjusting for pre-index monthly cost, age, gender, year of index treatment and Charlson Comorbidity Index.

Results:
Data from 3,153 FCM patients and 3,971 LDI patients were analyzed. Unadjusted mean number of outpatient visits increased numerically in the LDI group and unchanged for FCM, whereas ER visits and inpatient admissions decreased numerically for both treatment groups in the post-index period compared to baseline. After adjusting for covariates, post-index monthly inpatient costs [adjusted cost ratio (ACR)= 0.70,
p
<0.001], outpatient costs (ACR=0.74,
p
<0.001) and total costs (including IV iron) (ACR = 0.81,
p
<0.001) were significantly lower for FCM than LDI.

Conclusion:
Higher acquisition cost of FCM was offset by lower inpatient and outpatient costs in HF patients with IDA receiving FCM than LDI during the 12 months after IV iron treatment, resulting in significantly lower total healthcare costs for FCM compared to LDI.
Abstract 11370: Acute Myocarditis Following a Third Dose of COVID-19 mRNA Vaccination in Adults
Authors: Simone Anthony , Herald John , Chen Aiyu , Nayak Rohith , Shen Albert Yuh-Jer , Lee Mingsum S
Published: June 2023

Introduction:
The COVID-19 mRNA vaccines are effective in reducing COVID-19-related severe disease and death. Waning vaccine effectiveness has prompted the recommendation to administer additional (booster) doses. With additional doses of COVID-19 mRNA vaccines being recommended, it is essential to monitor its safety. Myocarditis has been reported following the second dose of COVID-19 mRNA vaccination. Whether administration of additional doses of COVID-19 vaccines further increases the risk of myocarditis is not known. This study aimed to evaluate whether a third dose of COVID-19 mRNA vaccine was associated with an increased risk of myocarditis in a large population-based cohort in California.

Methods:
We included individuals who received one to three doses of BNT162b2 (Pfizer) or mRNA-1273 (Moderna) mRNA vaccine between 12/14/2020 and 2/18/2022 in an integrated healthcare delivery system in the United States. Hospitalization for myocarditis within 21 days of vaccine administration was identified using electronic medical records.

Results:
Of 3,076,660 KPSC members who received at least one dose of COVID-19 mRNA vaccines, 2,916,739 (94.5%) received at least two doses, and 1,146,254 (47.0%) received three doses. The IRR for myocarditis was 0.86 (95% CI 0.31-1.93) for the first dose, 4.87 (95% CI 3.14-7.37) for the second dose, and 2.61 (1.13-5.29) for the third dose. The majority of myocarditis cases following the second and third dose occurred within seven days of vaccination.

Conclusion:
Myocarditis was a rare but serious event observed after the second or third dose of vaccination. Most cases presented within seven days of vaccination. The incidence of myocarditis following the third dose did not appear to be significantly higher than that observed after the second dose.
Abstract 11380: Exercise Induced ST Segment Elevation Caused by Coronary Vasospasm
Authors: Darbha Kaushik , Shen Yaoyun S , Whang David Christopher , Prabhu Sudhakar
Published: June 2023

Case Presentation:
A 52-year-old male with no known medical history was seen in the cardiology clinic for occasional pressure-like chest pain on exertion. Due to an intermediate pretest probability of CAD, ischemic workup with a nuclear perfusion exercise stress test was planned. Patient achieved maximum predicted heart rate after 12 minutes of exercising, with no anginal symptoms, ST segment changes or arrhythmias during the entire period. However, 3 minutes into the recovery phase, he developed chest pain and diaphoresis, with EKG now showing 7mm ST elevations in the inferior leads and BP falling to 77/56 mmHg. STEMI code was called, and patient was emergently taken to the cardiac cath lab for coronary angiogram and possible PCI. Angiogram found the coronary arteries to be non-obstructive but revealed vessels possibly having vasospasm. Intra coronary nitroglycerin was given with no further PCI. The patient’s symptoms subsided after the angiogram, and he remained asymptomatic thereupon and was eventually discharged on Verapamil and nitrate therapy.

Discussion:
Typically, vasospastic angina occurs at rest. Exercise induced and post-exercise recovery phase ST segment elevation on EKG is associated with severe atherosclerotic disease with significant coronary obstruction. However, exercise induced ST elevations in the post exercise recovery phase caused by non-obstructive, vasospastic coronary arteries, as seen in this patient, is a rare occurrence. The vasospasm is hypothesized to be due to coronary vascular smooth muscle hyperactivity and endothelial cell dysfunction. Treatment is usually with calcium channel blockers, nitrates and lifestyle modification such as smoking cessation and alcohol restriction. This case illustrates the importance of identifying the etiology of the angina, noting that post exercise ST segment elevations are not always associated with coronary vessel obstruction and vasospasm should be considered as a possible etiology.
Abstract 11396: Early-Onset Recurrent Malignant Arrhythmias in a Child With Hypertrophic Cardiomyopathy
Authors: Monereo Moreno Isabel , CARRERAS BLESA CARMEN , Tejero Hernández María Ángeles , Rodriguez Vazquez del Rey Maria del Mar , Molina Cuevas Blanca Alexandra , Garrido Jose Manuel , Casares Mediavilla Jaime , Yagüe Martín Marta , Macías Rosa , Jimenez-Jaimez Juan , Perin Francesca
Published: June 2023

Case presentation:
A male newborn was diagnosed with severe hypertrophic cardiomyopathy (HCM) because of a heart murmur. A genetic test identified the previously described pathogenic variant Arg719Trp in MHY7, which was not present in the parents. An additional variant in KCNE2, Ile57Thr, considered as a risk factor for acquired long QT, was found in the patient. Corrected QT interval was normal. At age 3, the child suffered cardiac arrest from which he was successfully defibrillated. Maximal wall thickness was 20 mm (z-score +18). With the patient weighing 18 kg, a subcutaneous implantable cardioverter defibrillator (s-ICD) was implanted with the two-incision technique and nadolol 2 mg/kg/day was started. After 3 appropriate ICD therapies in the following 3 months, amiodarone was associated to betablockers, with no QT prolongation. He suffered 8 more ventricular fibrillation-terminating ICD shocks in the following year, prompting the indication of thoracoscopic bilateral cardiac sympathectomy denervation (BCSD) and referring him for heart transplant evaluation. Following BCSD he was symptom free for 6 months, after which he presented with a prolonged cardiac arrest, needing sedation, 4 ICD shocks and external defibrillation to recover consciousness. After experiencing another electrical storm in the following month, he underwent successful cardiac transplantation at age 5.

Discussion:
This clinical case is noteworthy for different reasons. First of all, even if Arg719Trp mutation in MHY7 has been associated with full penetrance and early expressivity of HCM (mean age at diagnosis 24 years), the child presented with an extremely rare early-onset of recurrent fatal arrhythmias. The pathogenicity of the associated KNCE2 variant, Ile57Thr, has not yet been elucidated but it has been suggested to confer proarrhythmic susceptibility in the presence of other environmental or genetic risk factors. Another worth-mentioning clinical aspect is that s-ICD proved to be a safe and effective therapy in a child weighing much less than 30 kg. In this case in which heart transplant could not be avoided due to life-threatening arrhythmias, the benefit of the preservation of the central venous circulation with the absence of intravascular leads cannot be overstated.
Abstract 11422: Factors Associated With Improvement of Left Ventricular Function After Catheter Ablation for Atrial Fibrillation in Patients With Heart Failure: A Multicenter Cohort
Authors: Queiroz Franca Marcos Roberto , Nascimento Bruno R , Miranda Reynaldo , Silva Gustavo A , Franca Anna Terra , Moreira Henrique B , Fontes Vitor , Naback André D , Fraga Lucas L , Ruback Lucas R , Ribeiro Antonio L , Carmo Andre A
Published: June 2023

Introduction:
Catheter ablation is a well-established therapy for atrial fibrillation (AF), with a promising impact on heart failure (HF) outcomes. We aimed to assess the impact of AF ablation on echocardiographic and clinical parameters in patients with HF, and to assess factors associated with improvement of the left ventricular ejection fraction (LVEF).

Methods:
Patients with HF and LVEF<50% who underwent radiofrequency AF ablation in 5 high-volume Brazilian centers were prospectively enrolled. All patients underwent transthoracic echocardiography before the procedure and during follow-up, and the analysis by the examiner was considered. The primary outcome was LVEF normalization (≥50%) at follow-up. Clinical, echocardiographic, and procedural variables associated with the primary outcome were assessed by logistic regression.

Results:
From 2018 - 2022, 85 patients were included, being 59 (69%) males, mean age 66±12 years. Of these, 27 were in NYHA functional class 3/4 and 71 (83%) had persistent AF. Pre-procedural LVEF was 38±7%, and 25 (29%) had LVEF<35%. Complications occurred in 3 patients (2 vascular access and 1 endocarditis). In the 12±10 month follow-up, there was a substantial improvement of the LVEF to 54±14% (p<0.001), and 60 (71%) achieved LVEF normalization. 59 patients (69%) had LVEF improvement ≥10%, only 6 remained in NYHA class 3/4, and AF recurred in 13 (15%). Three patients died during follow-up, and none had LVEF normalization. Predictors of LVEF normalization were: pre-ablation LVEF (OR=1.24, 95%CI 1.12-1.37), left atrial diameter (OR=0.88, 95%CI 0.82-0.95), Chagasic etiology (OR=0.14, 95%CI 0.03-0.77) and indication of amiodarone (OR=0.26, 95%CI 0.09-0.72) and ACEi/ARB (OR=0.25, 95%CI 0.08-0.75, p=0.02). In the multivariable model, independent predictors were: baseline LVEF (OR=1.25, 95% CI 1.10-1.41, p<0.001), left atrial diameter (OR=0.88, 95%CI 0.79-0.98, p=0.02), Chagasic etiology (OR=0.07, 95%CI 0.01-0.74, p=0.03) and indication of ACEi/ARB: (OR: 0.11, 95%CI 0.02-0.63, p=0.01).

Conclusion:
AF ablation in patients with HF resulted in echocardiographic and functional improvement, with low complication rates. Less clinical severity and morpho-functional impairment associated with LVEF normalization.
Abstract 11464: Spectrum and Associated Factors for Coronary Artery Involvement in Kawasaki Disease versus Multisystem Inflammatory Syndrome in Children Associated With Covid-19
Authors: Lee Simon , Harahsheh Ashraf S , Portman Michael A , Fabi Marianna , Jain Supriya , El Ganzoury Mona , Dionne Audrey , Misra Nilanjana , Nowlen Todd , Elias Matthew , Fernandez-Cooke Elisa , Szmuszkovicz Jacqueline R , Orr William , Truong Dongngan , McHugh Kimberly E , Choueiter Nadine , Shah Surya , Manlhiot Cedric , Farid Pedrom , McCrindle Brian W
Published: June 2023

Introduction:
Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 share clinical features and are both associated with coronary artery (CA) involvement.

Methods:
From January 2020 through January 2022, n=2566 contemporaneous KD, MIS-C and acute COVID-19 pediatric patients from 39 sites in 8 countries were enrolled into the International KD Registry. The study population was confined to 875 MIS-C patients meeting CDC criteria with confirmed or probable COVID-19 infection, and 492 KD patients meeting AHA guideline criteria without COVID-19 infection who had sufficient echo data. CA involvement was defined by maximum Z score in any branch at any timepoint (maxCAZ). Associated factors for each diagnosis were determined with multivariable logistic regression for maxCAZ>2.

Results:
Median maxCAZ was higher for KD (+1.43) vs MIS-C patients (+1.33; p=0.004). The groups did not differ regarding the incidence of maxCAZ>2 (KD 26% vs MIS-C 24%; p=0.42), although MIS-C patients had less severe Z score categories of involvement (FIGURE). In univariate analyses, higher peak troponin I (p<0.05) and NTproBNP (p=0.06) were associated with maxCAZ>2 for MIS-C but not KD patients. Lower LV ejection fraction was likewise associated with maxCAZ>2 for MIS-C (p=0.009) but not KD patients. For KD patients, independent factors associated with maxCAZ>2 were male sex, age <6 months, greater total days of fever, shock presentation, and higher peak platelet count and CRP (c-statistic 0.69). In contrast, for MIS-C patients the only independent factor associated with maxCAZ>2 was male sex (c-statistic 0.56).

Conclusions:
Compared to KD patients, MIS-C patients have a similar incidence but lesser severity of CA involvement with few associated factors, male sex being the only one in common. CA involvement was significantly associated with higher cardiac biomarkers and lower LV ejection fraction for MIS-C patients only.
Abstract 11472: De-Escalation of Dual Antiplatelet Therapy in Elderly Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis
Authors: Fujisaki Tomohiro , Kuno Toshiki , Iwagami Masao , Miyamoto Yoshihisa , Takagi Hisato , Briasoulis Alexandros , Panaich Sidakpal , Latib Azeem , Kohsaka Shun
Published: June 2023

Background:
Recent randomized controlled trials (RCTs) have demonstrated the superiority of treating patients with acute coronary syndrome (ACS) with dual antiplatelet therapy (DAPT) uniform de-escalation strategy (i.e., switching from potent P2Y
12
inhibitors to clopidogrel one month after the event). However, it remains unclear if this strategy would be effective in elderly patients. We aimed to assess the efficacy of the available DAPT strategies, including the uniform de-escalation strategy, in ACS patients older than 65.

Methods:
We searched the PubMed, EMBASE, and Cochrane CENTRAL databases up to December 2021 for RCTs or subgroup analyses investigating DAPT strategies for elderly ACS patients (age ≥65 years) and conducted a network meta-analysis. The endpoint was net clinical benefit outcome, defined as a composite of major adverse cardiovascular events and bleeding. The P-score was used to rank the treatments.

Results:
Seven RCTs with 5,079 patients were included. The uniform de-escalation strategy was associated with a better net clinical benefit outcome (hazard ratio: 0.62; 95% confidence interval [0.41-0.92]) compared with DAPT using potent P2Y
12
inhibitors, and it was similarly effective compared with other DAPT strategies. There was no significant heterogeneity (
I
2
=0%;
p
=0.82) or inconsistency (
p
=0.40). The uniform de-escalation strategy was ranked as the most effective strategy (by P score) superior to DAPT using clopidogrel or low-dose prasugrel.

Conclusions:
The uniform de-escalation strategy was an effective strategy for older ACS patients. Compared with conventional DAPT using potent P2Y
12
inhibitors, this strategy decreased the composite of major adverse cardiovascular events and bleeding events.
Abstract 11481: Healthcare Resource Use, Early Benefit and Cost for North American Patients With HFrEF Most Likely to Benefit from Omecamtiv Mecarbil
Authors: Desai Nihar R , Greene Stephen J , Felker Michael , Solomon Scott D , Binder Gary , Divanji Punag , Gomes Daniel R , Kociol Robb , Teerlink John R
Published: June 2023

Introduction:
In GALACTIC-HF (NCT02929329), omecamtiv mecarbil (OM) added to guideline directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) reduced the risk of composite first HF event (HFE) or CV death. Increased risk with OM use was seen in patients with both digoxin use plus atrial fibrillation/flutter (AF) together at baseline (dig+AF), but not for patients with either factor alone. A previous analysis of GALACTIC-HF found OM to reduce resource utilization and costs among higher-risk patients with EF≤30% excluding dig+AF, but the impact in the subset within North America (N Am) is unclear.
Purpose:
To examine resource use, timing, and HFE costs for patients treated with OM in N Am.

Methods:
We analyzed risk of first and total HFE (hospitalization or IV diuretic use, all adjudicated), and events at 30 days post randomization and later, for the N Am region of GALACTIC-HF. Treatment effect was evaluated in the subgroup of GALACTIC-HF previously identified as most likely to benefit from OM: EF≤30% excluding dig+AF at baseline. We applied US costs per HFE from published studies inflated to 2021 USD, including $17,123 per HF hospitalization.

Results:
Of 8,232 trial patients, 1,386 (16.8%) were from N Am (1,220 US), of whom 4.6% had baseline dig+AF. In the N Am subgroup of 1,090 (78.6%) with EF≤30% excluding dig+AF, OM reduced risk of first HFE vs placebo (HR 0.81, 95% CI 0.67-0.98, p=0.027); >90% were hospitalizations. OM also reduced total HFE vs placebo (41.30 vs 55.46 per 100 pt-yrs, HR 0.76, 95%CI 0.61-0.94, p=0.010), with an ARR of 14.2 and a NNT of 7. Fewer HFE were seen with OM at 30 days (Incidence Rate Ratio [IRR] 0.56, p=0.035), 90 days (IRR 0.61, p=0.005) and throughout 3 yrs (IRR 0.78, p=0.029), with rising ARR. Cost reductions due to HFE avoided with OM averaged $420 / patient at 30 days, $928 at 90 days, and $6,052 (26.9% reduction) over 3 yrs.

Conclusions:
Among N Am patients with HFrEF≤30% and without dig+AF in GALACTIC-HF, OM significantly reduced HFEs with corresponding reductions in costs for HFEs. Clinically and statistically significant benefits were apparent within 30 days of OM initiation and continued through the trial. This large group of HFrEF patients may be where the clinical and economic benefit of OM is most evident.
Abstract 11484: Upregulation of Dynamin 2 Increases Mitochondrial Fission and Cell Proliferation in Pulmonary Arterial Hypertension
Authors: Das Gupta Asish , Chen Kuang-Huieh , Wu Danchen , Mewburn Jeffrey , Lima Patricia , Al-Qazazi Ruaa , Martin Ashley , Tian Lian , Archer Stephen L
Published: June 2023

Introduction:
The obstructive vasculopathy in pulmonary arterial hypertension (PAH) results in part from acquired mitochondrial changes in pulmonary arterial smooth muscle cells (PASMC), including increased mitotic fission. Mitotic fission, mitochondrial division which is coordinated with mitosis to equitably distribute mitochondria to daughter cells, is mediated by activation of dynamin-related protein 1 (Drp1). To complete mitochondrial fission, Drp1 requires assistance from the GTPase dynamin 2 (DNM2).

Hypothesis:
Pathological increase in DNM2 expression drives mitochondrial fission and proliferation of PAH PASMC.

Methods:
Immunoblots of human PASMC and immunohistochemistry and immunofluorescence of lung sections from human (n=5/group) and monocrotaline (MCT) rats with PAH (n=4-5/group) were used to assess the expression of DNM2. The effect of manipulating DNM2 on cell proliferation, cell cycle and apoptosis were assessed by flow cytometry. Mitochondrial fission was quantified using confocal imaging.

Results:
DNM2 protein expression is increased in human PAH PASMC. DNM2 is also increased in the media of small pulmonary arteries of PAH patients and MCT-PAH rats. Silencing DNM2 inhibited mitochondrial fission and reduced proliferation causing cell cycle arrest in G1/G0 phase. Silencing DNM2 in PAH PASMC also induced apoptosis. Conversely, augmenting DNM2 in normal PASMC induced mitochondrial fission and accelerated cell proliferation. miR-124-3p, a putative negative regulator of DNM2, is decreased in PAH PASMC. Augmenting miR-124-3p decreased DNM2 expression, inhibited proliferation and induced apoptosis in PAH PASMC.

Conclusion:
In health, DNM2 regulates mitochondrial fission whilst in disease, epigenetic upregulation of DNM2 increases mitotic fission, which drives pathologic proliferation and apoptosis resistance. The miR-124-3p-DNM2 pathway offers novel PAH therapeutic targets.
Abstract 11488: Comparative Effectiveness of PET and SPECT Myocardial Perfusion Imaging for Identification of Low-Risk Patients With Cardiometabolic Disease
Authors: Huck Daniel M , Weber Brittany N , Divakaran Sanjay , Brown Jenifer M , Lopez Diana M , do A. H. de Souza Ana Carolina , Laychak Shelby , Hainer Jon , Blankstein Ron , Dorbala Sharmila , Di Carli Marcelo F
Published: June 2023

Introduction:
The epidemiology of coronary artery disease (CAD) has shifted, with increasing cardiometabolic (CM) disease and decreasing obstructive CAD in patients referred for myocardial perfusion imaging (MPI). Coronary microvascular dysfunction, defined as impaired coronary flow reserve (CFR) by positron emission tomography (PET), has emerged as a key mediator of risk. Our objective was to assess whether CFR provides additive value to identify low-risk CM disease patients compared with single-photon emission computed tomography (SPECT) MPI.

Methods:
We retrospectively studied patients with CM disease (obesity, diabetes, or chronic kidney disease (CKD) stage ≥3) and without known CAD referred for PET or SPECT MPI at our center from 2006 to 2020. Annualized all-cause and cardiac mortality was determined from death certificates, and propensity-matched low-risk PET and SPECT patients were compared using Poisson and Cox regression.

Results:
CM disease was prevalent in consecutive MPI referrals without CAD including obesity (N=8869), diabetes (N=4896) and CKD (N=3555), and higher among PET MPI (p <0.001). Prevalence of summed stress score (SSS) >3 reflecting obstructive CAD was low (12%, 15% and 16%). Conversely, prevalence of CFR <2 was high (52%, 61% and 69%), reflecting impaired myocardial perfusion. In adjusted hazard analysis, normal MPI was associated with lower risk of all-cause and cardiac death (p <0.001). Normal PET (SSS ≤3 and CFR >2) was associated with lower all-cause death compared to normal SPECT
(Figure, A).
Normal PET and SPECT identified low-risk (<1%/year cardiac death) patients with obesity and diabetes, however those with CKD remained moderate-risk (1-3%/year)
(Figure, B).

Conclusion:
CM disease is common among patients without CAD referred for MPI. Normal PET and SPECT MPI identify a low-risk group for obesity and diabetes, but not CKD. PET with CFR has additive prognostic utility to identify low-risk individuals compared to SPECT.
Abstract 11499: Management of Mixed Aortic Valve Disease Patients: Can N-terminal Pro-Brain Natriuretic Peptide Ratio Improve Risk Assessment?
Authors: Bernard Jeremy , Jean Guillaume , Bienjonetti-Boudreau David , Jacques Frederic , Tastet Lionel , Salaun Erwan , Clavel Marie-Annick
Published: June 2023

Introduction:
Risk assessment of mixed aortic valve disease (MAVD: concomitant aortic stenosis [AS] and regurgitation [AR]) patients is challenging, especially in non-severe lesions. In fact, these patients often present LV dysfunction after aortic valve replacement (AVR), and concomitant non-severe lesions appear to have similar outcomes than severe AS.

Objective:
We aimed to evaluate the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) ratio in risk stratification of MAVD patients.

Methods:
A total of 582 consecutive MAVD patients (mean age 73±11 years, 63% men) with at least concomitant mild AS and AR in whom a measurement of NT-proBNP during the same episode of care was available were included. NT-proBNP ratio (i.e., plasma level divided by maximal normal values for age and sex derived from Mayo Clinic laboratory) was calculated. In subgroups analyses, patients were divided according to MAVD pattern (severe AS or AR [n=364] and non-severe AS/AR [n=218]) and according to treatment strategy (early AVR [i.e., ≤3 months, n=429] or initial medical treatment [MT; n=153]).

Results:
Baseline median NT-proBNP ratio was 3.5 (IQR: 1.2-10.0). A total of 105 patients died during a median follow-up of 5.6 (2.8-6.1) years. Overall, NT-proBNP ratio ≥3 was significantly associated with long-term all-cause mortality in multivariable analyses adjusted for clinical and echocardiographic parameters as well as AVR as a time-dependent variable
.
NT-proBNP-ratio also showed incremental prognostic value at 1, 2 and 5 years over EuroSCORE II and echocardiographic parameters (all, net reclassification index >0.45; p≤0.005). In all subgroups, NT-proBNP-ratio ≥3 remained independently associated with excess mortality (
severe AS or AR
- HR[95CI]: 3.30[1.54-7.05],
non-severe AS/AR
: 2.14[1.03-4.43],
early AVR
: 2.48[1.16-5.39],
initial MT
: 2.72[1.02-7.22]; all p≤0.04). In patients who underwent early AVR, NT-proBNP-ratio ≥3 was also associated with higher 30-days mortality (9[4%] vs. 1[0.5%], p=0.02).

Conclusions:
In this series of MAVD patients, NT-proBNP-ratio was a powerful predictor of mortality, even in non-severe lesions, early AVR and medically treated patients. AVR may be reasonable before reaching an NT-proBNP-ratio ≥3.
Abstract 11502: Exercise Stress Testing 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 the majority of cases are benign, an increasingly recognized sequela of MVP is sudden cardiac death (SCD), but triggers and risk factors for SCD are not well-defined. It is theorized that increased stretch on the papillary muscles due to MVP leads to papillary muscle fibrosis and cellular changes of local conduction properties, increasing the risk of ventricular arrhythmias and SCD.
Hypothesis
- We hypothesized that patients with MVP and SCD would have increased ventricular arrhythmias and ECG changes compared to MVP controls during exercise stress testing.

Methods -
The study population was generated from the Duke Epic. Patients were included if they had guideline-based diagnosis of MVP on echocardiogram or cardiac magnetic resonance imaging. Increase in ventricular arrhythmias during exercise was defined as >/= 10 PVCs per minute, multifocal PVCs, or >/= 2 PVCs in a row.

Results-
A total 2,513 patients with MVP were screened. 18 patients with SCD. Patients with SCD were younger [(47.22 +/- 12.2 ) vs. (58.0 +/- 18.7), p=0.02], more likely to be female (89.9% vs 64%, p=0.04) and had increased rate of bileaflet prolapse (72% vs. 40%, p=0.01) compared to controls. Patients with sudden cardiac death had either dynamic T wave changes or increased ventricular arrhythmias with stress testing versus controls [12/18 (66.7%) vs 17/75 (22.6%), p <0.001].

Conclusions -
Increased ventricular arrhythmias on exercise stress testing is associated with sudden cardiac death in mitral valve prolapse and may prove a useful tool for further risk stratification.
Abstract 11516: Heart Failure Patient Experiences With a Visualized Patient-Reported Outcome Monitoring Tool to Facilitate Beta-Blocker Decision-Making in an N-of-1 Trial
Authors: Mangal Sabrina , Hyder Maryam , Curtis Hannah , Zarzuela Kate , Kronish Ian , Maurer Mathew S , Lachs Mark , Safford Monika M , Goyal Parag
Published: June 2023

Introduction:
Emerging evidence suggests that beta-blockers may not be efficacious in preventing mortality in patients with heart failure with preserved ejection fraction (HFpEF) and could worsen exercise capacity. HFpEF patients’ symptoms often overlap with medication side effects, making precise decision-making about the need for beta-blockers a challenge.

Objective:
Evaluate patient attitudes toward using a patient-reported outcome (PRO) monitoring tool to facilitate shared decision-making about beta-blocker use in an N-of-1 clinical trial.

Methods:
Eligible HFpEF patients taking a beta-blocker were recruited from a heart failure clinic. Patients alternated between taking and not taking their beta-blocker for 2-week periods, with dedicated titration time in-between. Data were ascertained through exercise assessments, weekly/bi-weekly online PRO surveys, and remote vital measurements. Average symptom scores on and off beta-blocker were presented in a visualized report to patients, intended to facilitate a discussion about continuing vs. discontinuing their beta-blocker. We interviewed patients about feedback on study procedures and agency for decision-making at baseline and study visits. Interviews were recorded and transcribed. Three study team members analyzed interviews using directed content analysis.

Results:
To date, 9 patients completed the intervention, and 28 interviews were completed. Most participants were female and White (89%) with an average age of 78. Participants reported that their visualized PRO results were aligned their experiences, which reinforced their use of the tool and agency in beta-blocker decision-making (Table).

Conclusions:
Patients found that the visualized report helped to facilitate beta-blocker shared decision-making. Future research should evaluate the utility of integrating longitudinal PRO monitoring tools into usual care to facilitate individualized decisions about medications.
Abstract 11528: Neurotrophic Signaling Pathway Dysregulation, Cardiac Amyloidosis, and Innervation Impairment in the Tg2576 Model of Alzheimer's Disease
Authors: Elia Andrea , Parodi-Rullan Rebecca , Vazquez-Torres Rafael , Fossati Silvia
Published: June 2023

Alzheimer's disease (AD) is a complex and incurable neurodegenerative disorder characterized by cerebral amyloid β (Aβ) deposition and tau pathology, accompanied by a gradual loss of the two main neuromodulators, NGF and BDNF. The progressive degeneration of the cerebral neuro-signaling pathways triggers a gradual decline in neurotrophic factors with significant derangement of the peripheral nervous system. This may culminate in detrimental effects on other organs, including the heart. However, whether and how AD modulates neurotrophins, innervation, and amyloidosis in the cardiac tissue is still undefined. Here, we investigated, for the first time, cardiovascular remodeling and neuro signaling pathway dysregulation in a mouse model of Alzheimer’s disease. Hence, 12 months old Tg2576 transgenic mice, a model of cerebral amyloidosis, were compared to age-matched WT littermates. Echocardiographic analysis showed significant deterioration in LV function, evidenced by a severe decline both in ejection fraction and fraction shortening percentage in the Tg2576 group compared to WT mice. Tg2576 mice exhibited a relevant increase in interstitial fibrosis, with progressive accumulation of amyloid aggregates, resulting in severe cardiac nervous system dysfunction. The transgenic line showed a remarkable decrease in cardiac nerve fiber density, both adrenergic (stained with tyrosine hydroxylase- TH) and regenerating nerve endings (labeled with GAP-43) compared to the WT mice. This myocardial denervation was associated with a robust reduction in NGF and BDNF protein expression both at the neuronal and cardiac level, accompanied by a significant decline in GAP-43 activity in the heart and cerebral cortex lysates of Tg2576 mice. Additionally, human neuroblastoma cells (SH-SY5Y) challenged with human Aβ-40 or Aβ-42 oligomers showed a severe downregulation of both BDNF and GAP-43 protein levels. Overall, our evidence highlights a possible detrimental effect of cerebral amyloidosis on the peripheral nervous system and cardiac tissue, providing potential therapeutic targets, such as the neuro-signaling pathway, to prevent or delay some of the effects caused by AD on the cardiovascular system.
Abstract 11530: Edoxaban For Pediatric Patients With Cardiac Diseases: A Randomized, Open Label, Multicenter Study
Authors: Portman Michael A , Jacobs Jeffrey P , Newburger Jane W , Berger Felix , Grosso Michael A , Duggal Anil C , Goldenberg Neil A ,   ENNOBLE-ATE Trial Investigators
Published: June 2023

Introduction:
Standard of care (SOC) anticoagulation for thromboembolism (TE) prevention in patients <18 years old with cardiac disease includes low molecular weight heparins or vitamin K antagonists. Limited data exist comparing direct oral anticoagulants as edoxaban with conventional anticoagulants in this population.

Hypothesis:
Edoxaban is at least as safe as the current standard-of-care (low molecular weight heparins and/or vitamin K antagonists) with regard to the incidence of major and clinically relevant nonmajor bleeding in pediatric patients with cardiac diseases at risk of thromboembolism.

Methods:
We performed a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial in patients <18 years old with cardiac disease (ENNOBLE-ATE, NCT00687882). Children were randomized 2:1 to age- and weight-based oral edoxaban once-daily versus SOC for 3 months (main study). Randomization was stratified by concomitant use of aspirin and by underlying disease groups, as follow: history of Fontan procedure; Kawasaki disease; heart failure; other. Both groups continued in an extension with edoxaban through 1 year. The primary endpoint was adjudicated International Society on Thrombosis and Haemostasis defined clinically-relevant bleeding (CRB). The main secondary endpoint was a composite of symptomatic TE and asymptomatic intracardiac thrombosis.

Results:
We randomized 168 children from May 2018 to September 2021. The CRB event rates were similar between groups during the main period. One subject per group experienced a nonmajor CRB. Treatment-emergent adverse events occurred in 46.8% (51/109) with edoxaban and 41.4% (24/58) with SOC. One SOC subject experienced 2 TE events (DVT with PE). In 152 subjects continuing in the extension, one CRB event (0.7%; trauma related) and 4 TEs occurred (2.8%; 2 strokes and 2 coronary artery thromboses and/or myocardial infarctions).

Conclusion:
Bleeding and TE occurred rarely for both groups and during the extension,suggesting that edoxaban is safe and effective for TE prevention in this population. Once daily edoxaban may provide advantage for children considering difficulties with enoxaparin injections and food and drug interactions with warfarin.
Abstract 11566: Distribution and New Function of Na, K-ATPase and Its Phosphoprotein Regulator Phospholemman in Cardiac Myocytes
Authors: Guo Jin , Sung Yen L , Chen Peng-Sheng , Chen Zhenhui
Published: June 2023

Introduction:
Na, K-ATPase (NKA), regulated by phosphoprotein phospholemman (PLM), contributes to excitation-contraction via the Na,Ca-exchanger at cardiac T-tubules (TTs). It is known that the intercalated discs (IDs) contain concentrated specific Na channels and K channels, that rely on ion gradients set by NKA. Yet, the coordinated trafficking and localization of NKA and PLM in cardiomyocytes (CMs) remains incompletely understood,
Hypothesis:
NKA and PLM are concentrated in the ID and essential for cardiac conduction.

Methods:
We have made five antibodies (Abs) that specifically identify PLM (B8, PLM-N-term, and PLM-C-term) or NKA (NKA-α1 and Pan-α, recognizing both α1 and α2 subunits of NKA). Confocal immunofluorescence assays were used to determine the intracellular distribution of PLM and NKA. Optical mapping studies were performed in rabbit hearts.

Results:
These five Abs all displayed specific fluorescence signals in dog CMs that were more intense at the IDs than TTs. These signals were eliminated by competing peptides. B8 and NKA-α1 signals highly overlapped, with similar intensity ratios between ID and TT at ~3. Immunostaining of connexin 43, γ-catenin, or N-cadherin confirmed the co-localization of NKA and PLM to the ID. PLM and NKA co-enriched with ID protein markers in sarcolemma/ID membrane preparations. To corroborate the localization of PLM at the ID, we expressed dog PLM in rat CMs. By 30h post-infection, B8 detected newly synthesized dog PLM that paralleled the pattern of its steady-state distribution in tissue, with concentrated protein apparent at IDs (B8 fluorescence intensity ratio of ID/TT = 2.6 ± 0.5, 50CMs). Nocodazole prevented newly-made dog PLM trafficking to ID. Finally, optical mapping studies showed that the NKA inhibitor ouabain and digoxin significantly increased activation times in a dose-dependent manner (n=5 and 4 rabbits, respectively).

Conclusions:
The α1 subunit of NKA and PLM are each expressed at a ~3X higher concentration in ID compared to TT in CMs, contributing to cardiac conduction. Mechanisms of PLM and NKA protein trafficking to the two disparate subcellular sites, and associated effects of PLM regulation by adrenergic signaling, provide important new insights into the physiology of cardiac conduction.
Abstract 11578: A Case of Spontaneous Coronary Artery Dissection Masking as Acute Myopericarditis
Authors: Ahmed Ibrahim , Balinda ingabire , Julien Howard
Published: June 2023

Introduction:
Chest pain is a common reason for emergency room visits. Acute coronary syndrome (ACS) remains a high mortality etiology of chest pain. Spontaneous coronary artery dissection (SCAD) is a rare cause of ACS in the general population, but a relatively common cause of ACS in young women.

Case:
Patient is a 29-year-old female with history of anxiety and fibroids that presented with chest pain. She described the chest pain as sharp, substernal, non-radiating that lasted for 10 minutes after eating dinner. The pain improved with leaning forward and resolved when lying on her stomach. She had a second episode of chest pain after 2 hours with similar characteristics which lasted 10 minutes. She was 4 months post-partum. She reported having a sore throat 4 days prior to the presentation. Troponin peaked at 0.173. ECG showed diffuse ST-elevation and PR depression in V3-V6 I II III aVF. TTE showed LVEF 65% and no wall motion abnormalities. CTA coronary showed 50-60% narrowing of mid LAD. Cardiac MR showed mild hypokinesis of mid-anteroseptal wall with associated subendocardial to midmyocardial delayed enhancement with focal elevations in myocardial native T1 and T2, and LVEF 53%. Coronary catheterization showed 50-60% stenosis in the mid-LAD distal to the first diagonal artery, there was no improvement in the stenosis after administration of intra-coronary nitroglycerin, there were no septals noted to arise from this area, consistent with diagnosis of SCAD (figure 1).

Diagnosis:
On initial evaluation, the etiology of her chest pain appeared to be myopericarditis. However, using CTA coronary, cardiac MR and coronary catheterization findings, the pain was more consistent with type 1 NSTEMI in the setting of SCAD. Patient was started on IV heparin, metoprolol tartrate, and aspirin.

Conclusions:
SCAD is a life-threating and often missed etiology of ACS. It requires a high index of suspicion and should be in the differential diagnosis in young women presenting with chest pain.
Abstract 11580: Clinical Validation of a Smartphone Compatible 6L Electrocardiogram Device in Ambulatory Patients
Authors: Sample Karlie , Barber Rylee , Whyte Seabrook , Albert David E , Po Sunny S , Stavrakis Stavros
Published: June 2023

Introduction:
Novel ECG devices seek to facilitate easier obtainment of ECG recordings, while not compromising accuracy, compared to a standard clinical 12-L ECG. We aimed to compare the accuracy of the AliveCor Kardia 6L device with simultaneously recorded 12-L ECG recording with the patient in the same position.

Hypothesis:
The AliveCor Kardia 6L ECG device demonstrates data highly correlated with a standard 12-L ECG.

Methods:
We included patients seen in an outpatient cardiology clinic. ECG data using the Kardia 6L and a standard 12-L were obtained simultaneously in the seated position. Median beats for each method were compared using Pearson’s correlation.

Results:
One hundred patients (mean age 57±18, 55% female) were included. Lead aVL R wave amplitude (r= 0.99), T wave amplitude (r= 0.99), T wave axis (r= 0.96) QRS axis (r= 1.00), QRS duration (r= 0.94), and QT duration (r= 0.96) demonstrated excellent correlation between the two methods (Figure).

Conclusion:
The 6L Kardia device allows for accurate ECG measurements in ambulatory patients. This illustrates implications for the diagnosis of cardiac diseases, including left ventricular hypertrophy, in both clinical and nonclinical settings.
Abstract 11589: Total Artificial Heart Placement in a Case of Recurrent Ventricular Tachycardia Storm
Authors: Schwartz Brandon H , Hansen Breanna , Marano Paul , Cole Robert
Published: June 2023

Background:
Electrical storm is defined as three or more episodes of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) within a 24-hour period requiring termination by cardioversion, anti-tachycardia pacing (ATP) or defibrillation. It can be a particularly challenging syndrome to treat when refractory to standard of care therapies, which include antiarrhythmics, sedation, and ablation. We present a case of refractory electrical storm requiring total artificial heart placement (TAH) as a bridge to transplant.

Case:
A 65-year-old male with a history of idiopathic non-ischemic cardiomyopathy presented with VF arrest. After return of spontaneous circulation, he was admitted to the cardiac intensive care unit. Implantable cardioverter defibrillator (ICD) interrogation showed 38 shocks delivered over the prior two-week period. Coronary angiography showed no obstructive coronary disease and an intraaortic balloon pump (IABP) was placed for cardiogenic shock. He was intubated and sedated on fentanyl and propofol. He continued to have episodes of VT despite treatment with lidocaine, procainamide, and amiodarone drips. Further trials of paralysis and left stellate ganglion nerve block did not suppress his VT. Since the patient was refractory to all prior interventions, was deemed too unstable for VT ablation, and had a prolonged anticipated wait time for heart transplant, he underwent TAH placement as a bridge to heart transplant. He recovered well and eventually underwent successful heart transplant.

Discussion:
Management of electrical storm requires a stepwise approach including administration of antiarrhythmics, sedation, mechanical hemodynamic support, and catheter ablation. Our patient had incessant VT despite exhaustive medical and supportive therapies, but was too unstable to undergo VT ablation. In cases of refractory VT storm, definitive treatment with heart transplantation must be considered, but bridging patients to transplant poses a challenge. Our patient underwent TAH placement and was successfully stabilized prior to transplant. In centers with this capability, TAH should be recognized as a legitimate option in the pathway for VT, particularly with a long anticipated wait time for heart transplant.
Abstract 11642: Biologic Associations of the Senescence-Associated Secretory Phenotype (SASP) in Heart Failure (HF): Insights From Plasma Proteomics
Authors: Qian Chenao , Zamani Payman , Salman Oday , Jehangir Qasim , Cohen Jordana , Gunawardhana Kushan , Greenawalt Danielle , Zhao Lei , Chang Ching-Pin , Gordon David A , Ramirez-Valle Francisco , Cappola Thomas P , Chirinos Julio A
Published: June 2023

Background:
Cell senescence is involved in various age-related pathologies, including HF. The SASP is a characteristic secretory phenotype from senescent cells. We assessed biologic pathways associated with the SASP in human HF using a plasma proteomics approach.

Methods:
We measured 25 known SASP proteins among 2248 Penn HF Study (PHFS) participants using the SomaScan V4 assay. Factor analysis was used to extract the common variance among these proteins. Linear regression was used to assess the relationship of each factor to 4,746 other proteins, correcting for multiple comparisons, followed by pathway analyses.

Results:
Two underlying SASP factors were identified: Factor 1 was mainly represented by with matrix metallopeptidase 2, Tissue inhibitor of metalloproteinase 2 and Insulin Like Growth Factor Binding Protein 7. Factor 2 was correlated with cystatin C, Growth/differentiation factor-15 and Insulin-like Growth Factor Binding Protein-2. Both factors were associated with older age, male sex, lower BMI, higher prevalence of diabetes, higher prevalence of atrial fibrillation, lower estimated glomerular filtration rate and more advanced NYHA class. There was a lower prevalence of HF with recovered EF (as opposed to HF with reduced EF) among participants with higher levels of factor 1, but the prevalence of HF with preserved EF did not differ accordingly to levels of either factor. Factors 1 and 2 were associated with 1245 and 1509 proteins respectively. Both factors were associated with the coagulation system, complement system, acute phase response signaling, and retinoid X receptor (RXR) pathways that regulate cell metabolism (
Figure
).

Conclusion:
Higher levels of SASP are associated with older age, lower renal function and metabolic abnormalities in HF. Lower levels of SASP are associated with the presence of a recovered EF but not a preserved EF. Biologic pathways associated with SASP are predominantly related to inflammation and metabolic regulation.
Abstract 11658: Acute Coronary Syndrome After Insect Bite: A Systematic Review
Authors: Gupta Tanuj , capric violeta , Celenza-Salvatore Jessica , Jamaleddine Nader
Published: June 2023

Arthropod and insect bites/stings have been associated with the development of Acute Coronary Syndrome (ACS) in prior case reports. In this systematic analysis, we review 57 reported cases of ACS in patients that were exposed to arthropods, bee stings or insect bites, and provide a summary of these findings in Table 1. We then discuss Kounis Syndrome Type 1 or Type 2 as the proposed mechanism by which myocardial ischemia develops in this subset of patients, and the implications of this diagnosis on management. Kounis Syndrome Type 1 develops due to mast cell activation and histamine release provoking vasospasms and inducing myocardia injury in the absence of underlying coronary artery disease, as demonstrated in Figure 1A. Kounis Syndrome Type 2 develops due to inflammation induced plaque rupture and subsequent thrombus formation, as demonstrated in Figure 1B. In general, Kounis Syndrome should be suspected in patient’s presenting with the appropriate exposure, an allergic or anaphylactic response and/or unremarkable coronary angiogram (specific to Type 1). Once suspected, the use of coronary artery vasodilators, antihistamines, steroids and possibly Epinephrine should be considered in management. In this review, it was discovered that approximately 50% of cases received management consistent with Kounis Syndrome (targeted to allergic/anaphylactic symptoms) with appropriate clinical response, yet only 12% received the formal diagnosis, indicating this condition is underdiagnosed. Furthermore, 40% of patients that underwent coronary angiogram did not have CAD, indicating a possible Type 1 (vasospastic) etiology of ACS that may benefit from more targeted therapy.