bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14952: Lysosomal Regulation of Calcium and Iron Homeostasis and Ferroptosis in Mouse Cardiomyocytes
Authors: Pamarthi Sri Harika H , Fefelova Nadezhda , Gwathmey Judith K , Sadoshima Junichi , Xie Lai-Hua
Published: June 2023

Background:
Lysosomes are specific organelles that contain various digestive enzymes and also store both iron (Fe) and calcium (Ca). However, it is not known whether cytosolic and mitochondrial Fe and Ca handling and ferroptosis are modulated by lysosomal dysfunction. We aimed to evaluate the interaction between lysosomal, mitochondrial and cytosolic Ca and Fe dynamics and its relevance to cardiomyocyte function and ferroptosis.

Methods:
Left ventricular myocytes were enzymatically isolated from mouse hearts. Cytosolic Ca
i
was imaged using fluo-4-AM. Cytosolic Fe was determined with Phen green while mitochondrial Fe was measured using rhodamine B-[(1,10-phenanthroline-5-yl)-aminocarbonyl]benzyl ester (RPA). Mitochondrial membrane potential (Δ
Ψ
m
) was monitored by TMRM. Ferroptosis was analyzed using the Live/Dead cell viability assay.

Results:
Treatment with nicotinic acid dinucleotide phosphate (NAADP-AM 50 nM), an agonist of the two pore channel in the lysosomal membrane, increased the aptitude of the Ca
i
transient (1.94 ± 0.09 to 2.41 ± 0.14, n = 12,
p
< 0.05) and induced spontaneous Ca
i
waves. Diastolic Ca
i
became elevated (1.00 to 1.30 ± 0.10, n = 12,
p
< 0.05) in intact myocytes. Elevation of basal Ca
i
level and an increase in spontaneous Ca
i
wave amplitude and frequency were confirmed in saponin-permeabilized myocytes. NAADP also increased the level of cytosolic Fe. These results suggest both Ca and Fe are released from lysosomes into the cytosol by NAADP. Our previous studies have shown that mitochondrial Fe uptake is essential for Fe overload-induced ferroptosis in cardiac myocytes. Therefore, we further assessed how lysosome function affects mitochondrial Fe loading and induction of ferroptosis. We found that NAAPD treatment resulted in an elevation of mitochondrial Fe levels (by 28.4 ± 3.5 %, n=23,
p
<0.05), depolarization of Δ
Ψ
m
as well as resulted in an increased sensitivity to Fe overload-induced ferroptosis. Similar results were observed using GPN that causes selective disruption of lysosomes.

Conclusions:
Lysosomal dysfunction may contribute to mishandling of Ca and Fe in myocytes and promote the occurrence of ferroptosis. A lysosomal storage disorder mouse model (
i.e.
RagA/B KO) will be assessed in future studies.
Abstract 14958: Association of Smartwatch-Based Resting Heart Rate With Cardiorespiratory Fitness Measures From Cardiopulmonary Exercise Test in the Community
Authors: Zhang Yuankai , Wang Xuzhi , Pathiravasan Chathurangi H , Lin Honghuang , Borrelli Belinda , Spartano Nicole L , Benjamin Emelia J , McManus David D , Larson Martin , Ramachandran Vasan S , Lewis Gregory , Murabito JoAnne M , Nayor Matthew G , Liu Chunyu
Published: June 2023

Introduction:
Resting heart rate (HR) is an established predictor of cardiorespiratory fitness. Commercial smartwatches permit remote HR monitoring in real world settings over long periods of time, but the relations of smartwatch measured HR and cardiorespiratory fitness in the general public remain uncharacterized.
Objective
We aimed to examine the associations of resting HR measured with a smartwatch in the electronic Framingham Heart Study (eFHS) with multi-dimensional fitness assessment via cardiopulmonary exercise test (CPET). We hypothesized that participants with lower resting HR would have greater cardiorespiratory fitness.

Methods:
eFHS participants were enrolled at an FHS research exam (2016-2019) and provided with a study smartwatch that collected longitudinal HR data for up to 3 years. We identified participants’ HR measures in the sedentary state through a classification algorithm to calculate the average resting HR for each participant. At the same exam, participants underwent CPET performed on a cycle ergometer. Multivariable linear models were used to test the association of resting HR with CPET indices. We used P<0.05 for significance.

Results:
We included 1,051 participants (mean age 52±8 years, 59% women, mean resting HR 77±6 beats/min) with a median of 27,655 HR records for each individual, and median of 266 watch-wearing days. Higher individual resting HR was associated with a lower peak oxygen uptake (VO
2
; both in ml/kg/min and % predicted), lower VO
2
at the ventilatory anaerobic threshold (VAT), higher (adverse) ventilatory efficiency (VE/VCO
2
), and unfavorable blood pressure response to exercise (higher mean arterial pressure at 75 watts) (
Table
).

Conclusions:
Our findings suggest the feasibility of smartwatch-based HR assessment as an indicator of a broad array of cardiorespiratory fitness responses in the community, including measures of global fitness (peak VO
2
), ventilatory efficiency, and blood pressure response to exercise.
Abstract 14964: Photon Counting Computed Tomography for Aortic Valve Calcium Scoring in Contrast Enhanced Datasets of the Heart
Authors: Harmel Eva K , Braun Franziska , Risch Franka , Rippel Katharina , Scheurig Christian , Owais Tamer , Elvinger Sebastien , Girdauskas Evaldas , Kroencke Thomas , Raake Philip W , Schwarz Florian
Published: June 2023

Introduction:
The prognostic value of aortic valve calcification prior to transcatheter aortic valve replacement (TAVR) is well established. Its reliable quantification requires a non-contrast computed tomography (CT) of the heart (‘true non contrast’, TNC) which in this cohort is not regularly performed at all centers. Photon Counting Detector CT (PCD-CT) permits the routine derivation of ‘virtual non-contrast’ (VNC) and ‘virtual non-iodine’ (VNI) series from CT Angiography (CTA) acquisitions due to its intrinsic spectral sensitivity. These might render separate non-contrast acquisitions unnecessary.

Hypothesis:
We hypothetized that quantification of aortic valve calcification of VNC/ VNI series derived from CTA scans is feasable and correlates with calcium scores of TNC series.

Methods:
45 consecutive patients underwent pre TAVR CT on a novel PCD-CT (NAEOTOM Alpha, Siemens Healthineers, Erlangen, Germany) comprising a non-contrast CT of the heart, followed by a CTA of the heart, aorta, and iliac arteries. VNC series were derived from CTA acquisitions and two readers independently quantified aortic valve calcium scores (Agaston score) and calcium volumes on VNC-, VNI- and TNC-series.

Results:
A total of 41 patients (41.46% female) were included in the study. In comparison with aortic valve calcium scores and volume scores derived from TNC series (i.e., 2800[2075-3681] vs. 2206[1645-2894] mm3), those derived from VNC (i.e., 752[390-1357] vs. 653.3[319.5-1052.3] mm3) and VNI (i.e., 1986[1270-3278] vs. 1515[971-2480] mm3) series were consistently lower but correlation was excellent for both, i.e., calcium and volume score, respectively (r’s: 0.96 and 0.96 for VNC; r’s: 0.92 and 0.91 for VNI, p< 0.05).

Conclusions:
Our initial patient experience with TAVR planning CT on a novel PCD-CT showed signficant correlation of aortic valve calcium scores and volumes derived from VNC and VNI series, as compared with those derived from TNC series, thus rendering non-contrast acquisitions for TAVR planning redundant.
Abstract 14984: Transient Constrictive Pericarditis: Pericardiectomy to the Rescue
Authors: Syed Alveena B , Yaker Zachary S , Reyaldeen Reza , Krywanczyk Alison , Agrawal Ankit , Majid Muhammad , Kumar Ashwin , Furqan Muhammad M , Yesilyaprak Abdullah , Klein Allan L
Published: June 2023

Case Presentation:
A 47 years old male presented with progressive dyspnea, bilateral leg and abdominal swelling, weight gain, and intermittent low-grade fever. He had a history of hypertension and chronic lymphocytic pericarditis complicated by an episode of constrictive pericarditis. Exam showed jugular venous pressure of 10 cmH2O, pericardial knock, and abdominal distention. Inflammatory markers were elevated (CRP 87.3 mg/dL, ESR 29 mm/hr). Echo showed abnormal increase in septal longitudinal motion and Doppler interrogation of the hepatic veins showed diastolic flow reversal at the end of expiration. Cardiac MRI showed pericardial thickening and circumferential delayed pericardial enhancement. Patient was diagnosed with transient constrictive pericarditis (TCP) and was treated with ibuprofen, colchicine, and prednisone and had improvement in his symptoms and inflammatory markers. However, he experienced another recurrence 6 months later and underwent pericardiectomy. Pathology showed organized fibrosis overlying the parietal fibrosa layer, mild neovascularization and perivascular chronic inflammation, confirming the diagnosis of TCP. After pericardiectomy, patient had significant symptomatic improvement and returned to his baseline activity level. Postoperative echo showed normalization of annulus longitudinal motion and cardiac MRI showed near resolution of pericardial delayed enhancement. He was successfully tapered off of his anti-inflammatory regimen.

Discussion:
TCP is a sub-type of constrictive pericarditis characterized by pathological findings of pericardial edema, acute or subacute inflammation, and fibrin deposition, as opposed to the fixed pericardial fibrosis and calcification seen in constrictive pericarditis. Constriction may resolve spontaneously, and anti-inflammatory therapy is the mainstay of treatment but in refractory cases like these, pericardiectomy comes to the rescue.
Abstract 14985: Artificial Intelligence Based Heart Rate Variability Analysis for Sudden Cardiac Arrest Risk Prediction
Authors: Keidar Noam , Yaniv Yael , Bronstein Alex , Eidelsztein Gal
Published: June 2023

Introduction:
Sudden Cardiac Arrest (SCA) is an unexpected life-threatening loss of cardiac function potentially leading to sudden cardiac death (SCD). It accounts for a half of cardiac mortality, posing a major public health problem. While SCA can be treated with implantable cardioverter defibrillators (ICD), most (80%) SCDs occur in relatively low risk patients, for whom risk benefit ratio of an ICD is unfavorable. Therefore, novel methods to identify high risk individuals and the time on which their risk is high may facilitate prevention of SCD.

Methods
: Long (~24h) ECG recordings from individuals who had an SCA on record (n=20), patients with other arrhythmias (n=84) and from healthy individuals (n=17) from PhysioNet databases were analyzed to extract inter beat intervals (IBI). For each step in the IBI series, 120 last IBIs were used to calculate 19 indices that quantify short term heart rate variability (HRV). An artificial intelligence model named temporal convolutional network (TCN) was used to continuously assess the risk of a future VF event based on the current HRV estimate combined with few hours of history of previous HRV estimates. Training and testing of the TCN was done using Leave One Out testing done twice. Patients being classified at any point in the record as high risk were considered high risk.

Results
: Only patients from the SCA population, and none from the other arrythmia and healthy patients, were classified as high risk (PPV=100%). On average, sensitivity and specificity were 62.5% and 100% respectively

Conclusions
: In this preliminary retrospective analysis, artificial intelligence based HRV analysis identified risk for a SCA event in the following 24 hours with high specificity. Larger cohort and prospective testing are needed to assess the clinical utility of such systems.
Abstract 15: Hypoxia As Therapy For Mitochond​Rial Injury Following Cardiac Arrest
Authors: Piao Lin , Fang Yong-hu , Wu Rongxue R , Archer Stephen L , Sharp Willard W
Published: June 2023

Introduction:
Mitochondrial injury occurs following cardiac arrest (CA) and contributes to myocardial stunning and anoxic brain injury. Hypoxia has been proposed as a therapeutic strategy for neurodegenerative diseases associated with mitochondrial respiration defects, but its benefits in the post-CA setting remain unexplored. Here, we hypothesized mild hypoxia as therapy for post-CA mitochondrial injury.

Methods and Results:
Mice underwent brief asystolic CA (12 min) followed by cardiopulmonary resuscitation (CPR). One hour following successful CPR, mice were randomized to receive a brief episode (6 hours) of hyperoxia (33% O
2
), normoxia (21% O
2
), or hypoxia (10% O
2
) in an environmental chamber. Post exposure, the mice were returned to room air (21% O
2
). Hypoxia improved myocardial fractional shortening compared to normoxia and hyperoxia (Hypoxia: 45.6±2.3 %, Normoxia: 40.0±0.8 %, Hyperoxia: 29.0±4.0 %, n=5, P<0.05, respectively). Hypoxia also elevated neurological scores (Hypoxia: 8.4±1.3, Hyperoxia: 5.6±1.2, n=5, P<0.05) 48 hours post CA compared to hyperoxia. Ten-day survival was prolonged by hypoxia (Hypoxia: 87.5 %, Normoxia: 62.5 %, Hyperoxia: 12.5 %, n=10, P<0.05, respectively). Hypoxia also improved mitochondrial function (28% increase in basic oxygen consumption and 49% increase in ATP-related oxygen consumption, n=3, P<0.05, respectively) and a 20% decrease in ROS production (n=6, P<0.05) compared to normoxia.

Conclusion:
This study has two important findings:

First

, we demonstrate that oxygen availability in the early post-CA period is a critical determinant of long-term post-CA outcomes.

Second

, we show that mild hypoxic therapy in the early post-CA period improves early mitochondrial function and long-term post-CA outcomes. These findings reveal an important oxygen-dependent therapeutic window following resuscitation from CA that has implications for post-CA critical care.
Abstract 15002: Real-World Healthcare Resource Utilization Among US Patients With Atrial Fibrillation Receiving Dronedarone versus Ablation as 1st-Line Therapy
Authors: Greene Stephen J , Schilsky Samantha , Roberts Andrew W , Kabadi Shaum M , MCKINDLEY David , PREBLICK RON , Rashkin Jason , Leeming Reno , Sajedian Renee , Russo Andrea M
Published: June 2023

Introduction:
Catheter ablation is used increasingly as a 1st-line (1L) alternative to antiarrhythmic drugs (AAD) including dronedarone in patients with atrial fibrillation (AF). Healthcare resource utilization (HCRU)-related costs with dronedarone vs 1L ablation are unknown.

Methods:
We conducted a retrospective, observational cohort study using Optum Clinformatics Data Mart® from Jan 2012-Jan 2022 among US adults with AF and no prior rhythm control therapy who received new AAD therapy with dronedarone (index: date of incident dronedarone fill) vs those who received 1L ablation, or a non-dronedarone AAD followed by ablation within 3 mo (index: date of first recorded ablation or AAD). Patients were required to have ≥24 mo of pre-index data, and ≥3 mo follow-up. Patients in the 1L ablation cohort were propensity score matched 2:1 to the dronedarone cohort. Mean payer costs per patient per month (PPPM) during the 24-mo post-index period were calculated for total HCRU, inpatient visits, emergency room (ER) visits, outpatient physicians’ office visits, and all outpatient visits, and compared by zero-inflated negative binomial (ZINB) regression model.

Results:
Post-matching, the dronedarone (n=1440) and 1L ablation (n=2253) cohorts had similar baseline characteristics (mean age at index: 68.4 vs 67.7 years; male: 57.7% vs 59.3%; mean time from AF diagnosis to index: 80.2 vs 91.6 days; Charlson comorbidity index: 2.3 vs 2.2; CHADS2-VASc score: 3.4 vs 3.2). Mean PPPM costs were lower with dronedarone vs 1L ablation for all-cause total HCRU, inpatient visits, any outpatient visit, ER visit, and outpatient office visit (Table). ZINB analyses showed significant cost differences for all-cause total HCRU and any outpatient visit events.

Conclusion:
In patients with AF and no prior rhythm control therapy, 1L dronedarone was associated with lower total HCRU and outpatient visit costs during 24-mo follow-up vs 1L ablation; future studies will assess cost-effectiveness.
Abstract 15006: Imaging the Mitochondrial Nucleoid Body in Pulmonary Arterial Hypertension Reveals Changes in Nucleoid Body Distribution and Composition in Human Pulmonary Artery Smooth Muscle Cells
Authors: Rossi Jenna A , Dunham-Snary Kimberly J , Mewburn Jeffrey D , Archer Stephen L
Published: June 2023

Introduction:
Pulmonary arterial hypertension (PAH) exhibits excessive proliferation of pulmonary artery smooth muscle cells (PASMC). This is related to mitochondrial abnormalities, including a metabolic shift to aerobic glycolysis, and increased mitochondrial fragmentation. Mitochondrial DNA (mtDNA) encodes 13 proteins critical to mitochondrial function and is supported by multi-protein complexes called nucleoid bodies (NB) comprised of key mtDNA maintenance proteins. Previous data shows increased mtDNA damage and increased NB protein levels in PAH vs control PASMC. This seems to suggest an attempted compensatory response to mtDNA damage in PAH. We aim to identify NB composition and distribution changes in PAH. We hypothesize that NB structure and distribution throughout the mitochondrial network are dysregulated in PAH.

Methods:
NBs were visualized in control and PAH PASMC (n=15 per group). Cells were loaded with MitoTracker Deep Red (mitochondrial matrix dye) and visualized using stimulated emission depletion (STED) microscopy. We simultaneously imaged mtDNA and NB proteins TFAM, POLG and SSBP. NB protein distribution was quantified by comparing the rates of mtDNA-protein interactions per mitochondrial area.

Results:
On visualization of PASMC, mitochondrial fragmentation was evident in PAH vs control. Qualitative findings in PAH PASMC included increased heterogeneity of NB size (diameter) and spatial distribution in PAH compared to control. IF quantitation showed decreased mtDNA/cell (193±20 vs 326±28 mtDNA/cell, p<0.05) and increased SSBP (0.91±0.07 vs 0.59±0.37 SSBP/mtDNA, p<0.05) in PAH cells. These results are consistent with previous findings.

Conclusion:
These findings suggest a compensatory remodeling of NB in PASMC and is an important step in characterizing the NB shape, distribution, and composition in PAH. These findings will direct experiments analyzing gene and protein expression to further elucidate the role of NB in PAH.
Abstract 15009: Detection of a Low Ventricular Stiffness With Preserved Ejection Fraction Phenotype in Single Ventricle Physiology
Authors: Chowdhury Shahryar M , Graham Eric M , Menick Donald R , Atz Andrew M
Published: June 2023

Introduction:
Patients with single ventricle physiology frequently demonstrate decreased exercise tolerance after the Fontan operation. The objective of this study was to investigate the contribution of ventricular stiffness to exercise function in these patients.

Hypothesis:
We hypothesized that ventricular stiffness, both extremes of high and low stiffness, would be associated with exercise tolerance in Fontan patients.

Methods:
We previously validated an echocardiographic measure of ventricular stiffness, lateral Doppler E: tissue Doppler e’/end-diastolic volume (lateral E:e’/EDV) in children. Core-lab echocardiograms and exercise test results were obtained from the publicly-available Pediatric Heart Network Fontan Cross-sectional Study database. Exercise function was quantified as % predicted VO
2
. Ejection fraction (EF) was considered abnormal if < 50%. Diastolic function was defined as high stiffness if the lateral E:e’/EDV was > 90th percentile or low stiffness if < 10th percentile. Patients were divided into four groups: 1 = normal EF and normal diastolic function, 2 = decreased EF with normal diastolic function, 3 = normal EF with high ventricular stiffness, and 4 = normal EF with low ventricular stiffness.

Results:
239 patients (61% left, 29% right, 10% mixed ventricular dominance) had EF, lateral E:e’/EDV, and VO
2
measured. Differences between groups are reported in the Table.

Conclusion:
Single ventricle patients with both high and low stiffness and preserved EF had worse exercise capacity than patients with both normal and abnormal EF. To our knowledge, this is the first study detecting a low stiffness heart failure phenotype in single ventricle physiology. Future studies should further investigate the pathophysiologic mechanisms that lead to these extremes of stiffness in Fontan patients.
Abstract 15031: Anticoagulation Status and Risk of Stroke Following Leak-Closure Procedure for Residual Leak After Occlusion of the Left Atrial Appendage in Patients With Atrial Fibrillation
Authors: Mohanty Sanghamitra , Della Rocca Domenico G , Baho Karim , Shetty Sai Shishir , QUINTERO MAYEDO ANGEL , MacDonald Bryan , Gianni Carola , Asfour Issa , Kessler Danielle , Bassiouny Mohamed , Gallinghouse G , Burkhardt John , Horton Rodney , Al-Ahmad Amin , Di Biase Luigi , Natale Andrea
Published: June 2023

Introduction:
Studies have shown a correlation between leaks following left atrial appendage occlusion procedure and thromboembolic (TE) events.

Hypothesis:
We investigated the benefits of leak-closure in terms of safe discontinuation of oral anticoagulation (OAC) and minimization of the stroke-risk.

Methods:
Consecutive patients undergoing leak-closure procedure at our institution were included in the analysis. Procedures included closure with endovascular coils or Amplatzer plug or by using radiofrequency ablation (RFA). Persistence of the leak was verified by multiplane transesophageal echocardiogram (TEE) using color Doppler. Follow-up TEE were performed 60 ± 15 days post-procedure to evaluate LAA closure and patients were kept on OAC until then. After confirmation of closure, they were transitioned to ASA 81 mg/day. All patients were monitored quarterly for thromboembolic (TE) events.

Results:
A total of 139 post-Watchman patients undergoing leak-closure were included in the analysis (RFA: 10, Amplatzer plug: 5, coil-closure: 124). Pre-coil closure TE events were reported in 7 (5%) subjects. Moderate (3-4 mm) and severe (≥5 mm) leak were detected in 118 (85%) and 21 (15%) patients respectively. After the leak-closure procedure, complete sealing of the leak was confirmed at the follow-up TEE in 138 (99.2%) patients. Figure 1 shows significant reduction in TE events following the leak-closure procedure (p=0.031). During the 2-year follow-up period, six deaths were reported due to unrelated causes. Of the remaining 133 subjects, two patients were on DAPT because of history of coronary artery disease, two with prior stroke were on half-dose OAC and the remaining 129 (95.8%) were on ASA 81 mg/day. No TE events were reported in patients that transitioned to ASA.

Conclusions:
In this series, successful percutaneous leak-closure not only minimized the risk of stroke but also enabled the majority of patients to discontinue OAC without any TE events.
Abstract 15035: LIN28a Extends Regenerative Window of the Postnatal Heart and Promotes New Myocyte Formation in the Adult Heart After Injury via Lncrna-h19
Authors: Rigaud Vagner O , Hoy Robert , Kurian Justin , Zarka Clare , Behanan Michael , Brosious Isabella , Pennise Jennifer , Patel Tej , Kraus Lindsay , Mohsin Sadia , Houser Steven R , Khan Mohsin
Published: June 2023

The neonatal heart holds a remarkable regenerative capacity that is lost within the first week of life coinciding with a profound shift in cardiomyocyte (CM) metabolism, and CM cell cycle arrest. Whether reprogramming metabolism reactivates CM cell cycle enhancing cardiac function and repair after injury is unknown. Here, we identify a novel role for the RNA-binding protein LIN28a, a master regulator of cellular metabolism, in cardiac development and repair following injury. LIN28a was found as primarily active during cardiac development and rapidly decreases after birth. Injury to the neonatal heart, but not in adults, reactivates LIN28a leading to regenerative processes while LIN28a inhibition with small molecules attenuated pro-reparative effects of the postnatal heart. LIN28a reintroduction at P1, P3, P5, P7, and P14 decreased maturation-associated polyploidization, nucleation, and cell size, enhancing CM cell cycle activity and number of CMs per hearts in LIN28a transgenic pups compared to WT littermates. Moreover, LIN28a overexpression extended CM cell cycle activity and regenerative processes beyond P7 resulting in increased cardiac function 30 days after apical resection. In the adult heart, LIN28a overexpression promoted formation of new CMs and enhanced cardiac function, and survival in mice 12 weeks after myocardial infarction compared to WT littermate controls. Furthermore, the percentage of mononucleated CMs in the LIN28a overexpressing hearts was positively correlated to better cardiac functional recovery after injury. Mechanistically, CMs overexpressing LIN28a showed increased glycolytic metabolism while its attenuation by 2-DG reverted LIN28a-induced enhancement in CM cell cycle activity in adult hearts 4 days after injury. LIN28a immunoprecipitation followed by RNA sequencing in CMs isolated from LIN28a injured hearts identified lncRNA-H19 as its most significantly altered target. Ablation of lncRNA-H19 blunted LIN28a-induced enhancement on CM metabolism and cell cycle activity. Collectively, LIN28a reprograms CM metabolism enhancing cell cycle activity in the injured heart and pro-reparative processes thereby linking CM metabolism to the regulation of ploidy/nucleation and repair in the heart.
Abstract 15045: Impact of Left Ventricular Assist Device (LVAD) Type on Arrhythmic Outcomes in Patients With Continuous Flow LVADs
Authors: Gopinathannair Rakesh , Lakkireddy Dhanunjaya , Pothineni Naga , Roukoz Henri , Bhan Adarsh , Ahmed Mustafa , Ahmed Adnan , Charate Rishi , Atkins Donita , Padmanabhan Deepak , Gautam Sandeep , Gautam Sandeep , Mar Philip L , Slaughter Mark S , Trivedi Jaimin
Published: June 2023

Introduction:
Cardiac arrhythmias are common in continuous flow left ventricular assist device (LVAD) recipients. The impact of axial vs. intrapericardial centrifugal LVAD pumps on arrhythmia incidence and associated clinical outcomes is unclear.

Hypothesis:
This multicenter study evaluated the impact of LVAD type (axial vs. centrifugal) on incidence of atrial and ventricular arrhythmias, ICD shocks and mortality in LVAD patients.

Methods:
Analysis was done on 536 patients who underwent LVAD implantation at 5 US centers from 2008 to 2016. The groups were divided based on their LVAD type (axial - HeartMate II [HMII, n=433] vs. centrifugal - HeartWare (HW, n=103). Baseline characteristics as well as incidence of post-LVAD atrial arrhythmias (PL-AA), ventricular arrhythmias (PL-VA) and ICD shocks were analyzed in these groups. Multivariable Cox Regression analysis was used to identify predictors of survival.

Results:
Of 536 patients, 433 had HMII axial LVAD and 103 had HW centrifugal VAD implant. At baseline, HMII group had more males, higher proportion of CRT-D and higher prevalence of AA (Table 1A). Left ventricular dimensions were similar between groups. During a median follow-up of 537 days of LVAD support, incidence of PL-VA and ICD shocks were significantly higher in the HM2 group compared to HW group whereas incidence of PL-AA was not significantly different (Table 1A). In multivariable Cox Regression analysis, LVAD indication was the only variable that predicted survival (Table 1B). Type of LVAD (axial vs. centrifugal) was not associated with survival (HMII vs. HW - HR 1.04, P=0.48).

Conclusions:
In this multi-center continuous flow LVAD cohort, axial HM2 VAD patients had a higher incidence of PL-VA and ICD shocks. Type of LVAD (axial vs. centrifugal) was not associated with survival.
Abstract 15054: Genome Wide Association Study of Coronary Microvascular Disease Assessed by Cardiac Perfusion Positron Emission Tomography
Authors: Verma Shefali , Guare Lindsay , Irving Brett ,   Regeneron Genetics Cntr,   PennMedicine BioBank, Levin Michael , Guerraty Marie A
Published: June 2023

Introduction:
Coronary Microvascular Disease (CMVD), defined as disease of the coronary pre-arterioles, arterioles, and capillaries, accounts for 30-50% of the burden of ischemic heart disease. However, little is known about the pathogenesis, and there are no directed therapies for CMVD. Perfusion cardiac PET allows for the quantitative assessment of myocardial blood flow (MBF) at rest and stress and MBF reserve (MBFR) and represents the most clinical advanced non-invasive imaging modality for CMVD.

Hypothesis:
Here we perform the first genome-wide association study (GWAS) for CMVD using cardiac PET MBF parameters.

Methods:
Rest and stress MBF and MBFR were measured using Rubidium-82 cardiac perfusion PET stress tests which were obtained as part of routine clinical care. We performed a GWAS in 383 samples of European (EUR) and 539 samples of African ancestry (AFR) in the Penn Medicine Biobank using MBF values and REGENIE software. Models were adjusted for age, sex, age
2
, age x sex, 5 principal components, and batch corresponding to phenotype extraction. Additionally fine mapping was performed for loci with P-value < 1e-05 using implementation of SuSiE in the polyfun package by integrating gene expression and functional annotations from heart ventricular, atrium, aorta, and coronary artery tissues in the EpiMap database.

Results:
We identified 10 variants in AFR ancestry for MBFR at p-value < 5e-7. Among the top hits, our results identified novel signals in variants mapping to
LOC105374051, UNC13A, RPL21P130, ATP6V0A2, CCSER1, and MDFI
, among others. We also identified 4 variants in AFR and 1 in EUR for rest MBF and 3 variants in AFR and 1 in EUR for stress MBF phenotypes, including loci near
ARHGAP18 and ARHGAP22
. Fine mapping identified 4 loci in AFR for MBFR including
NRP1, ERC1, RN7SKP148, and SCL15A4
. In sex-stratified analyses, we found that variants were more strongly associated with PET-derived MBF phenotypes in AFR women than in AFR men and in EUR men relative to EUR women.

Conclusions:
Our study identified several variants associated with perfusion PET MBF parameters in populations of EUR and AFR ancestry, some of which represent putative CMVD loci. This work yields novel insights into mechanisms of CMVD.
Abstract 15064: Health Status Profiles in Patients With New or Worsening Peripheral Artery Disease Symptoms and One-Year Hospitalization Risk
Authors: Scierka Lindsey , Labrosciano Clementine , Bradley Brooklyn , Fitridge Robert , Spertus John , Mena-Hurtado Carlos , Smolderen Kim G
Published: June 2023

Introduction:
Patients with peripheral artery disease (PAD) have an elevated risk of cardiovascular and limb-related events, resulting in increased hospitalizations and costs. In patients with new or worsening PAD symptoms, we used patients’ baseline health status information as a way of identifying patients’ hospitalization.

Methods:
We included patients enrolled in the United States cohort of the multicenter PORTRAIT Registry from June 2011 and December 2015. PAD-specific health status was assessed at baseline using the Peripheral Artery Questionnaire (PAQ), with scores of 0-100 (higher scores indicating better health status). The primary outcome was 1-year all-cause hospitalizations. The association between PAQ score category (0 to <25, 25 to <50, 50 to <75, and 75-100 used as the reference category) and cumulative hospitalization risk was derived using proportional means models, adjusting for demographics and comorbidities.

Results:
Of the 797 patients (mean age of 68.6±9.7 years, 41.9% were female), 272 (34%) were admitted over 12 months of follow up. Compared with the best health status (PAQ 75-100), scoring in the lowest health status category (PAQ < 25) was associated with a higher risk of 1-year hospitalization (4.8% vs. 48.6%, adjusted hazard ratio 2.86 [95% confidence interval = 1.61-5.08]). A dose-response relationship was noted for the association between lower health status and increased risk of hospitalization. Similar associations were found for all PAQ domains except symptom stability.

Conclusion:
In patients with symptomatic PAD, presenting health status profiles were a robust predictor of 1-year hospitalization risk, with a >2-fold difference between those in the lower versus upper scoring segments. Given the potentially modifiable nature of health status, there is a need for monitoring and multicomponent interventions that can improve patients’ health status and potentially also their hospitalization risk.
Abstract 15081: The Viscoelastic Yield Stress of Blood is Negatively Associated With Pulmonary Blood Flow in the Fontan Circulation
Authors: Suriany Silvie , Liu Honglei , Cheng Andrew L , Detterich Jon A
Published: June 2023

Introduction:
In the Fontan (FN) circulation pulmonary blood flow (Qp) is passive, resulting in severely decreased shear rate and velocity in pulmonary arteries to the point of stasis. Yield stress (YS) is the shear stress required for blood to transition from stasis to a moving fluid. Therefore, YS may be a determinant of Qp in FN. We evaluated YS in patients with FN and Glenn (GLN) circulations and whether increased YS is associated with decreased Qp.

Methods:
We enrolled 20 patients with biventricular (2V) congenital heart disease (CHD) and 41 patients with single ventricle CHD (19 FN and 22 GLN) who were undergoing a clinically indicated cardiac catheterization. Two patients were excluded due to pulmonary vascular disease. We obtained blood samples at the time of catheterization and measured blood viscosity across shear rates 1 s
-1
to 1000 s
-1
using a Rheolog viscometer We calculated YS by curve-fitting of the viscosity measurements to a Casson fluid model.

Hypothesis:
We hypothesize that higher yield stress will be associated with lower pulmonary blood flow in Fontan circulation.

Results:
The FN group was the oldest and had the largest BSA (FN>2V>GLN; p<0.0001). Hematocrit was highest in GLN (GLN>FN>2V; p<). Blood viscosity was higher across all shear rates in GLN compared to both FN and 2V (p<0.001 for all shear rates) and higher in FN than 2V from 1 s
-1
to 150 s
-1
(p<0.05 for all shear rates). YS was highest in GLN (GLN>FN>2V; p< ). YS was negatively associated with Qp in both FN (R2 0.33, p=0.02) and GLN (R2 0.2, p=0.038), but not 2V (see Figure). Hematocrit was negatively associated with Qp in 2V (R2 0.34, p=0.028) and trended toward negative association in FN (R2 0.27, p=0.099), but not in GLN. Stepwise regression of Hct and YS vs Qp in FN demonstrated YS as the primary predictor of Qp.

Conclusions:
Our data demonstrate that the yield stress of blood derived from the Casson fluid model is a significant determinant of pulmonary blood flow in FN circulation.
Abstract 15083: Chronicity of Heart Failure, In-Hospital Clinical Trajectory, and Post-Discharge Outcomes Among Patients Hospitalized for Heart Failure
Authors: Pierce Jacob B , Maqsood Muhammad H , Khan Mohammad S , Minhas Abdul M , Felker Michael , Greene Stephen J
Published: June 2023

Introduction:
Among patients hospitalized for HF, patients hospitalized with worsening chronic heart failure (WCHF) are at increased risk for morbidity and mortality compared with those who are recently diagnosed with HF. Whether there are differences in clinical course during hospitalization for HF is unclear.

Methods:
We pooled 735 participants hospitalized for HF in the DOSE, CARRESS, and ROSE trials. We grouped participants by whether HF was recently diagnosed (≤12 months) or WHCF (>12 months). We compared changes in congestion, kidney function, and symptoms during hospitalization, as well as early post-discharge kidney and mortality outcomes.

Results:
Overall, 132 (18%) had recently diagnosed HF and 603 (82%) had WCHF. Compared with WCHF, patients with recently diagnosed HF tended to have lower serum creatinine and higher systolic blood pressure, ejection fraction, and serum NT-proBNP (all p<0.05). In the first 72 hours, changes in body weight, global well-being visual analog scale, serum creatinine, and serum NT-proBNP, as well as net fluid loss were similar between patients with recently diagnosed versus WCHF (all p>0.15) (
Figure
). Recently diagnosed HF showed improved dyspnea at 72 hours (p=0.03). There was no difference in change in serum creatinine from baseline to 60 days (p=0.75). There was a trend toward significantly increased odds of mortality during study follow-up (adjusted odds ratio 1.96 [95% confidence interval 0.97-3.94], p=0.06).

Conclusion:
Patients hospitalized for recently diagnosed and WCHF have generally similar in-hospital clinical trajectories, and similar changes in kidney function early post-discharge. Despite these similarities and adjustment for other clinical factors, patients with WCHF remain at increased risk for post-discharge mortality as compared with patients who are more recently diagnosed.
Abstract 15086: Impact of Vegan Meal Kits on Cardiometabolic Endpoints: A Randomized, Controlled Clinical Trial
Authors: Pham Kevin , SKY Joseph , Hill Robert , Haynes Andrew , Pak Sahra , Shah Sachin A
Published: June 2023

Background:
While vegan diets have shown cardiometabolic health benefits, implementing such diets can pose a practical challenge. Boxed meal delivery kits have emerged in the market to meet this gap. We evaluated the impact of a vegan boxed meal kit (VBK) compared to a standard omnivorous boxed meal kit (OBK) on cardiometabolic endpoints.

Methods:
This was a randomized, controlled, parallel-designed trial. Overweight (BMI ≥25 kg/m
2
) military beneficiaries on a standard omnivorous diet were randomized to consume a VBK or OBK for 4 weeks. The meal kits provided lunch and dinner. The primary endpoint was change from baseline at 4 weeks in calculated low-density lipoproteins (LDL-c). Other lipid parameters and weight were also evaluated.

Results:
A total of 54 participants (38.8±11.6 years) completed the VBK (N=27) and OBK (N=27) groups. Baseline LDL-c in VBK and OBK groups were 109.7±34.2 mg/dL and 101.0±34.1 mg/dL respectively. Baseline weight in VBK and OBK groups were 202.8±39.9 pounds and 197.6±46.4 pounds respectively. LDL-c changed from baseline in the VBK and OBK groups by -10.0±19.3% and +1.0±15.0%, respectively (p=0.028). Weight changed from baseline in the VBK and OBK by -2.7±2.1% and -0.39±1.69%, respectively (p<0.001). Total cholesterol was significantly lower in the VBK, while no differences were seen in HDL and TG. Dietary compliance was excellent.

Conclusion:
Vegan boxed meal kits significantly reduced LDL-c and weight in a 4-week period, and may serve as a tool to implement cardiometabolic dietary interventions.

Disclaimer:
The views expressed in this material are of the authors and do not reflect the official policy or position of the U.S. Government, the Department of Defense, the Department of the Air Force, or the University of the Pacific. The voluntary, fully informed consent of the subjects used in this research was obtained as required by 32 CFR 219 and DODI3216.02_AFI40-402, Protection of Human Subjects and Adherence to Ethical Standards in Air Force Supported Research.
Abstract 151: Effect Of Time From Collapse To Prehospital Return Of Spontaneous Circulation On Neurologically Favorable Survival In Patients With Out-of-hospital Cardiac Arrest At Nighttime Versus Daytime
Authors: Tateishi Kazuya , Saito Yuichi , Kitahara Hideki , Tahara Yoshio , Nonogi Hiroshi , Yonemoto Naohiro , Nagao Ken , Ikeda Takanori , Sato Naoki , Kobayashi Yoshio ,   the JCS-ReSS Investigators
Published: June 2023

Background:
Survival with favorable neurological outcomes is one of the goals in patients with out-of-hospital cardiac arrest (OHCA). Although previous studies have shown that a chance of neurologically intact survival was significantly lower at nighttime than at daytime in patients with OHCA, details are uncertain. The aim of this study was to evaluate the effect of time from collapse to prehospital return of spontaneous circulation (ROSC) on neurologically favorable survival in patients with OHCA at nighttime versus daytime.

Methods:
Using a nationwide OHCA registry database from 2005 to 2020 in Japan, a cohort of 1,902,986 patients with OHCA were retrospectively screened. In the present study, a total of 128,180 patients with witnessed OHCA who achieved prehospital ROSC were included. Nighttime was defined as 6:00 pm through 5:59 am. Neurologically favorable survival was defined as cerebral performance category score of 1 or 2 at 1 month.

Results:
Patients with witnessed OHCA at nighttime were likely to be younger (70.3±16.0 vs. 72.7±15.3 years, p<0.001) and to have shorter time from collapse to resuscitation (8.1±7.3 vs. 8.6±7.2 min, p<0.001) than those at daytime (6:00 am to 5:59 pm), while time from collapse to ROSC was longer in patients with OHCA at nighttime (18.3±12.7 vs. 17.9±12.2 min, p<0.001). Overall, nighttime OHCA was associated with a lower rate of neurologically favorable survival at 1 months than daytime OHCA (30.9% vs. 31.8%, p<0.001). The negative effect of nighttime OHCA on neurologically favorable survival was observed especially when the time from collapse to prehospital ROSC was within the range of 5 to 10 minutes (Figure).

Conclusions:
Nighttime rather than daytime OHCA was associated with neurological impaired survival or death at 1 month. The negative effect of nighttime OHCA was pronounced when prehospital ROSC was achieved 5 to 10 minutes after collapse.
Abstract 15103: Stratifying Coronary Artery Disease (CAD) GWAS Loci Using Cardiac Perfusion Positron Emission Tomography to Identify Loci for Coronary Microvascular Disease
Authors: Verma Shefali , Guare Lindsay , Irving Brett ,   Regeneron Genetics Cntr,   PennMedicine BioBank, Levin Michael , Guerraty Marie A
Published: June 2023

Introduction:
Coronary Microvascular Disease (CMVD), defined as disease of the coronary pre-arterioles, arterioles, and capillaries, accounts for 30-50% of the burden of Ischemic Heart Disease (IHD). CAD GWAS studies have identified more than 235 loci, however, the populations enrolled represent heterogeneous IHD with inclusion criteria that include ischemia without confirmation of obstructive CAD (Ischemia with non-obstructed Coronary Arteries).

Hypothesis:
We hypothesize that CAD GWAS studies are really IHD GWAS studies and a subset of patients enrolled have CMVD as the etiology of their ischemia. Thus several CAD GWAS loci may be CMVD loci. Here we use quantitative measures of myocardial blood flow (MBF) and MBF reserve (MBFR) from cardiac Perfusion PET studies to stratify known CAD loci for CMVD.

Methods:
We performed a genomic association study for 235 known CAD loci in 383 samples of European (EUR) and 539 samples of African ancestry (AFR) in the Penn Medicine Biobank using clinical Rubidium-82 PET using REGENIE software. Models were adjusted for age, sex, age
2
, age x sex, 5 principal components, and batch corresponding to phenotype extraction. We examined regions within 250kb of known CAD loci for association with PET-derived MBF and MBFR. Bonferroni corrected P-value < 2.13e-4 was considered significant.

Results:
We found 40 loci in patients of AFR ancestry and 11 CAD loci in patients of EUR ancestry that were significantly associated with MBFR, including several genes which are known to play a role in microvasculature function and angiogenesis (VEGFa, FLT1, and FGF1). Stress MBF values have been shown to reflect epicardial CAD. We found 28 loci in patients of AFR ancestry and 12 loci in patients of EUR ancestry which were significantly associated with stress MBF and are mostly distinct from loci associated with MBFR. One notable exception is PRDM16 which was highly significant in both phenotypes.

Conclusions:
Our study sub-stratified variants previously associated with CAD to identify those that may be involved in CMVD. Several genes known to be involved in microvasculature function (VEGFa, FLT1, and FGF1) were putative CMVD genes. PRDM16 was associated with stress MBF and MBFR. This work prioritizes CAD loci for further study of mechanisms of CMVD.
Abstract 15104: Diverse Associations Between Long-Term Body Mass Index Variability and Midlife Cognitive Function: The Bogalusa Heart Study
Authors: Kang Soo Jung , De Anda-Duran Ileana , Fernandez Camilo A , Bazzano Lydia A
Published: June 2023

Introduction:
Evidence shows that individual variation of body weight over time may have a role in explaining cognitive decline later in life independent from obesity status. Yet, the effect of long-term variability from childhood on midlife cognitive function (CF), as well as race differences remains unclear. This study examines this association among Black and White middle-aged individuals from a community cohort in Bogalusa, Louisiana.

Methods:
A total of 1,268 participants (59.5% women, 34.4% Black) from the Bogalusa Heart Study who had
>
4 BMI measurements from childhood (mean age: 9.5 ± 3.5), and complete neuropsychological (NP) tests assessment to evaluate CF at midlife (48.2 ± 5.2) were studied. CF was measured with a global cognitive score (GCS). Long-term BMI variability was computed as standard deviation (SD), coefficient of variation (CV), deviation from age-predicted values (DEV), and residual SD (RSD). Regression models were used to evaluate the associations between BMI variability and GCS. Covariates included age, sex, race, cardiovascular risk factors, depression, class II obesity (BMI ≥ 35kg/m
2
) at midlife, alcohol use, education and employment status. Race, sex and BMI variability interactions were evaluated.

Results:
Overall, higher DEV and RSD [Beta (SE): -0.30 (0.10); p = 0.003, and – 0.17 (0.08); p = 0.025, respectively] was associated with lower GCS. Interactions between SD, CV, DEV, and RSD with race were significant, but not with sex. Stratified analyses of the relationship between BMI variability measures and GCS showed the following result among White participants [DEV Beta (SE): -0.25 (0.10); p = 0.01] and Black participants [DEV Beta (SE): -0.03 (0.13); p = 0.81], respectively.

Conclusion:
We identified diverse associations between BMI variability from childhood and cognitive function in midlife. Although Black participants appear more resilient to the influence of BMI variability on CF in midlife, further studies are needed to identify the nature of this complex phenomenon and its potential to contribute to vascular causes of cognitive decline and dementia.