bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12102: Concomitance of Diabetes Mellitus and Prior Myocardial Infarction Associated With Poor Clinical Outcomes in Patients With Atrial Fibrillation: The Fushimi AF Registry
Authors: Ide Yuya , Ogawa Hisashi , Nakanishi Yumiko , Minami Kimihito , Ishigami Kenjiro , Ikeda Syuhei , DOI KOSUKE , Hamatani Yasuhiro , Yoshizawa Takashi , Fujino Akiko , Ishii Mitsuru , Iguchi Moritake , Masunaga Nobutoyo , Esato Masahiro , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Akao Masaharu
Published: June 2023

Background
: Patients with diabetes mellitus (DM) have high risk of cardiovascular events such as cardiovascular death, stroke, heart failure and so on. Patients with history of myocardial infarction (MI) are also at high risk. The outcomes of patients with nonvalvular atrial fibrillation (NVAF) who have both DM and history of MI are unclear.

Methods
: From the Fushimi AF registry, we obtained NVAF patients who had both DM and history of MI (DM+MI+: N=107), either DM or history of MI (DM-MI+: N=156, and DM+MI-: (N=935), and neither DM nor history of MI (DM-MI-: N=3,197). Major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality were evaluated. MACCE was defined as composite events of cardiovascular death, myocardial infarction, stroke, and admission for heart failure.

Results:
The median follow-up period was 1,851 (interquartile range: 790-2,924) days. DM+MI+ patients were often male and had more heart failure, chronic renal disease, dyslipidemia, hypertension, and paroxysmal AF than other patients. DM+MI+patients had also higher risk scores (CHADS
2
, CHA
2
DS
2
-VASc and HAS-BLED scores). DM+MI+ patients had significantly higher incidence (% per patient-year) of MACCE and all-cause mortality than others (Figure A and B. MACCE: DM+MI+ 18.8%, DM-MI+ 8.0%, DM+MI- 6.1%, DM-/MI- 4.9%, log rank P<0.001, all-cause mortality: 10.2%, 6.1%, 5.2%, 4.5%, respectively, log rank P<0.001). In multivariate analysis, DM+MI+ was significantly associated with the incidence of MACCE compared with DM-/MI- (adjusted hazard ratio [95% confidence interval], 1.97 [1.36-2.87], P<0.001), although DM-MI+ and DM+MI had no association with it. In addition, DM+MI+ had no significant association with the incidence of all-cause mortality after multivariate adjustment.

Conclusion:
Patients with NVAF who have both DM and history of MI had more comorbidities and had significant association with adverse cardiovascular events.
Abstract 12110: The Multi-Racial Clinical and Familial Characteristics of Early and Late Onset Atrial Flutter
Authors: Ongtengco Ana S , Qiao Victor , Hassaballa Hatem , Allababidi Malek , Dhingra Shaurya , Mishra Atreya , Deshpande Ashwini , Chen Yining , Al-azzam Bahaa , Konda Sreenivas , Tofovic David , Darbar Dawood
Published: June 2023

Introduction:
Studies in Whites of European descent have shown that atrial fibrillation (AF) have a strong genetic component especially in probands with early-onset (EO) AF. However, the role of family history in the pathogenesis of EO atrial flutter (EOAFL) across race-ethnicity remains unclear. Here, we sought to determine if African American, European American, and Hispanic/Latino probands with EOAFL have a higher rate of arrhythmia recurrence in first-degree family members than ethnically-matched patients with late-onset AFL (LOAFL).

Methods:
In this cohort study, 917 adults with AFL were identified between 2015 and 2021 across 3 sites in the Chicagoland area. EOAFL was defined as AFL occurring before 60 years of age. Primary analysis of reported family history in first-degree relatives with sensitivity analysis restricted to those in whom a family history was confirmed by medical record review and electrocardiogram was done.

Results:
Those with EOAFL were more overweight, Black or White, and had more comorbidities (
Table 1
). Multivariate analysis showed that BMI ≥ 40 kg/m
2
(odds ratio [OR]: 5.4; 95% confidence interval [CI]: 3.2-9.4,
p
<0.001) and a family history (OR: 3.7; 95% CI: 2.1-6.9,
P
<0.001) carried the highest adjusted odds of EOAFL followed by alcohol use (OR: 2.1; 95% CI: 1.5-3.0,
P
<0.001), Black race (OR: 1.6; 95% CI: 1.1-2.3,
P
=0.021), and heart failure (OR: 1.4; 95% CI: 1-1.9,
P
=0.03). Adjusting for effect modification on the association of family history and race, among Whites, the odds of EOAFL in patients with family history was 6.1 (95% CI: 2.1-22.3,
P
=0.002) comparative to those with no family history, and among Blacks, it was 4.9 (95% CI: 1.6-6.1,
P
=0.021).

Conclusion:
Obesity and family history were strongly associated with EOAFL. Whites with EOAFL were more likely to have a first-degree relative with AF/AFL when compared to Blacks or Hispanics/Latinos. These findings support genetic predisposition to EOAFL across all 3 races.
Abstract 12115: TAVR Endocarditis Complicated by Aortic Root Pseudoaneurysm
Authors: Bienstock Solomon , El-Hamamsy Ismail , Plitt Anna , Sanz Javier , LaRocca Gina , Kini Annapoorna , Al-kazaz Mohamed
Published: June 2023

Case Presentation:
An 83-year-old man with hypertension, hyperlipidemia, atrial fibrillation, non-obstructive CAD, and severe AS status post TAVR 4 months prior was transferred from an outside hospital with reported persistent fever for one week. He had no other procedure recently including dental work. He was found to have staphylococcus epidermidis bacteremia in multiple blood cultures. His outside hospital TEE showed pulsatility of the non-coronary sinus with possible vegetations on the noncoronary cusp of the TAVR. On physical examination, he was afebrile, normotensive, and well appearing. His cardiovascular examination, laboratory tests, and chest radiograph were unremarkable, and he denied any chest pain or shortness of breath. His ECG revealed rate-controlled atrial fibrillation. A cardiac CTA revealed a 6 mm mobile hypodense thickening of the non-coronary prosthetic cusp, suspicious for vegetation and a contrast opacifying outpouching in the aortic root near the aorto-mitral curtain, suspicious for pseudoaneurysm. The patient underwent TAVR explantation, pseudoaneurysm exclusion, and AVR using a 23 mm bioprosthesis
(Figure).
He was discharged 8 days later on antibiotic treatment. At follow-up, the patient felt well with no complaints.

Discussion:
TAVR endocarditis with resulting aortic root pseudoaneurysm is an immensely rare entity, where there is lack of clinical data with regards to management. Guidelines of prosthetic valve endocarditis (for both TAVR and SAVR) recommend surgical treatment in such cases, although this recommendation was mostly based on the SAVR literature and many patients who undergo TAVR are at higher surgical risk at baseline. Recent studies on TAVR explantation showcase the risky nature of surgery in these patients, with high mortality rates, making treatment decisions less clear. Careful multidisciplinary discussion of risk and benefits is vital to guide clinical decision making in these complex patients.
Abstract 12122: Five-Year Serial Measurement of the Intermountain Mortality Risk Score for Population Health Assessment Reveals Personalized Temporal Trajectories of Differential Longevity Over Two Decades
Authors: Horne Benjamin D , Bledsoe Joseph R , Muhlestein Joseph B , Woller Scott C , Knowlton Kirk U , Majercik Sarah , Bair Tami L , Snow Gregory L , Lloyd James F , Le Viet T , Bennett Sterling T , Ronnow Brianna S , May Heidi T , Anderson Jeffrey L
Published: June 2023

Introduction:
Health, wellness, and healthcare are most effectively and efficiently managed when health status is quantitatively measured. The Intermountain Mortality Risk Score (IMRS) is a well-validated low-cost decision tool calculated from the complete blood count and basic metabolic profile that can be electronically deployed to inform clinician or patient actions. This study evaluated if 3 serial IMRS measurements improved mortality prediction.

Methods:
In 119,379 Intermountain Healthcare outpatients, inpatients, and emergency patients, baseline (BL) IMRS was calculated in 1999-2005. Of those, the following were excluded: 22,678 who died prior to having 3 IMRS measurements and 38,228 survivors who at 5 years (y) post-BL did not have 3 IMRS. In the study cohort of 58,473 patients, a 1
st
follow-up (1F) IMRS was available 1.49±0.79 y post-BL (range 1-4 y), and a 2
nd
follow-up (2F) IMRS at 3.75±0.80 y post-BL (range 2-5 y). Patients had 13.4±1.7 y of follow-up after 2F (range: 9.3-18.7 y), with total follow-up post-BL of 17.2±1.5 y (range: 14.3-20.7 y).

Results:
Overall, 26,693 patients died (45.7%) after 2F. In females, IMRS for decedents vs. survivors was, respectively, 11.3±3.9 vs 6.3±4.0 at BL, 11.1±3.9 vs 5.7±4.0 at 1F, and 12.2±4.2 vs 6.1±4.0 at 2F; differences in males were similar to those results (all p<0.001). Relative risks for IMRS categories are shown in the Table. C-statistics for females were c= 0.815, 0.834, 0.858 for BL, 1F, and 2F, with 0.872 for a sum of the 3 IMRS (results were similar for males, with absolute c 0.06-0.08 lower).

Conclusions:
IMRS predicted substantial risk differences at each of 3 timepoints, but the IMRS trajectory (including declines in IMRS) revealed by the sequence of IMRS measurements better personalized risk assessment. When risk level and direction are considered together, critical junctures in a person’s health journey may be revealed, empowering earlier or more intensive prevention, diagnostic testing, and interventions.
Abstract 12130: Cardiac Arrest as a Result of Anaphylactic Reaction From MAb Infusion for COVID-19
Authors: Abdulrahman ZEINAB , Azeez Hayder , McCullough Jocelyn , weber andrew , Temkin Marilyn
Published: June 2023

Introduction:
Anaphylaxis is a severe, life-threatening, systemic hypersensitivity reaction. Severe cases may result in complete obstruction of the airway and cardiovascular collapse. Monoclonal antibody (MAb) products with anaphylactic potential are being used to treat COVID-19 through an FDA Emergency Use Authorization (EUA).

Case Presentation:
An 86-year-old male was referred to our hospital for thoracentesis. Medical history was significant for CLL, Atrial fibrillation, and type 2 diabetes mellitus. He had completed a 3-dose vaccination series for COVID-19. On the physical he was eutensive, afebrile, and was noted to have diminished breath sounds at the right lower lobe. Chest Xray showed right sided moderate pleural effusion. EKG showed atrial fibrillation. Thoracentesis was performed without complication. After this procedure, the patient’s PCR for COVID-19 returned positive. He met the criteria for MAb infusion and was provided bebtelovimab 175 mg intravenously. One minute later the patient became unresponsive, cyanotic, and bradycardic to 38 beats per minute. ACLS protocol was administered and 1mg atropine provided. After 1 cycle, ROSC was achieved and the patient was endotracheally intubated due to persistent altered consciousness. The patient was transferred to the ICU requiring intravenous vasopressors and remained intubated for 24 hours. He was extubated to Bilevel NIV, and weaned in the ambient air. TTE was performed and showed severe pulmonary HTN and an EF of 60%-65%. He was provided diuresis and discharged from the ICU.

Conclusion:
Anti-SARS-CoV-2 MAbs have been used for patients with mild to moderate COVID-19 who are hospitalized for reasons other than COVID-19 per FDA EUA criteria. Such treatments have been known to cause anaphylaxis in the past, although due to a dearth of complications, they may be underappreciated. This case brings attention to the serious anaphylactic reactions that can be caused by MAb and demonstrates the need for observation with ACLS capable equipment post-infusion.
Abstract 12145: Cell Surface Trafficking and Functional Deep Mutational Scans of the Potassium Channel Gene KCNE1
Authors: Muhammad Ayesha , Yang Tao , Calandranis Maria , Hall Lynn , Matreyek Kenneth A , Fowler Douglas M , Roden Dan M , Glazer Andrew M
Published: June 2023

Introduction:
Loss of function variants in
KCNE1
cause type 5 Long QT Syndrome. Deep mutational scanning is a highly multiplexed method to assay the function of thousands of genetic variants.

Hypothesis:
A deep mutational scan of
KCNE1
will identify variants that disrupt KCNE1 function and may lead to Long QT Syndrome.

Methods:
A comprehensive library of nearly all possible
KCNE1
variants was generated by inverse PCR. The library was integrated in a one-variant-per-cell format into HEK293 landing pad cells expressing the KCNE1 partner
KCNQ1
. To assess surface trafficking, cells expressing an HA-tagged
KCNE1
variant library were stained with an anti-HA antibody, FACS sorted into 4 equal bins, and deep sequenced. For each variant, a weighted average of variant counts across the 4 bins was calculated. To assess channel function, the
KCNE1
library was introduced into landing pad cells expressing a gain of function S140G KCNQ1 variant, which causes KCNE1-dependent K+ efflux and cell death, for 12 days. Functional scores for each variant were calculated as a normalized ratio of initial and day 12 counts.

Results:
The
KCNE1
library had 88% of 2,451 possible missense variants. The results of the 2 assays indicate that the KCNE1 C-terminus is dispensable for trafficking but not function. Missense variant trafficking scores (n=1,886) were normally distributed (0.93+/-0.37, mean+/-SD); 277 loss- and 183 gain-of-trafficking variants were identified. Missense variant functional scores were bimodally distributed. The functional assay identified loss of function variants with trafficking-deficient or trafficking-normal scores (likely gating variants). The assays identified structurally important regions, such as an N-terminal salt bridge, a transmembrane helix at residues 47-59 resistant to hydrophilic variants, and a cytoplasmic amphipathic helix at residues 90-114 resistant to hydrophobic variants. Manual patch clamp results for 4 previously studied and 4 novel variants correlated with deep mutational scanning scores.

Conclusions:
Two deep mutational scans of
KCNE1
identified variants that disrupt channel or function. This dataset elucidates structure-function relationships and may help predict LQT5 variant pathogenicity.
Abstract 12148: A New Perspective in the Management of Paroxysmal Atrial Fibrillation: Dual Anti-Arrhythmic Medications
Authors: Al-zakhari Rana , mousa safa , Sheets Nicholas , Appiah-Kubi Edmund , Owusu-Antwi Philipa , Isber Ryan , Isber Nidal
Published: June 2023

Introduction:
Atrial fibrillation is the most common disorder of cardiac rhythm, which is often associated with a high risk of morbidity and mortality. Antiarrhythmic medications (AAMs) continue to be the mainstay in the treatment of paroxysmal atrial fibrillation. However, the use of these medications has been limited by their modest anti-arrhythmic efficacy.

Hypothesis:
We hypothesized that dual AAMs (sodium/potassium channels blockers) improve the chance of maintaining sinus rhythm and decrease the need for catheter ablation when compared to single AAM.

Methods:
We conducted a retrospective observational study; we reviewed medical records of 150 patients with paroxysmal atrial fibrillation over five years at our hospital in New York. We collected the following data: age, sex, comorbidities, electrocardiogram findings, ejection fraction by echocardiography, classes of AAMs, duration and response to treatments. A successful response was defined as the absence of symptoms and the presence of sinus rhythm on electrocardiogram. A failed response was defined as persistence of symptoms and/or atrial fibrillation on electrocardiogram and the subsequent need for catheter ablation.

Results:
86 patients met the inclusion criteria in our analysis. The average age of the patinets was 71.06 years. 45 patients were given the dual AAMs of either amiodarone+flecainide or dronedarone+flecainide, and were treated for an average of 15.4 months. 41 patients received a single AAM then catheter ablation if needed. A chi-square test was performed. X
2
=18.9429, p<.0001. Patients taking dual AAMs were very likely to maintain sinus rhythm and less likely to need catheter ablation (Figure).

Conclusions:
Our preliminary results demonstrate that patients who receive dual AAMs are significantly less likely to need catheter ablation than those who receive single AAM. Well-designed prospective studies are needed to further explore the use of dual AAM therapy and its clinical impact.
Abstract 12152: Recurrent Cerebrovascular Accidents Following Myocardial Infarction With Mechanical Rupture
Authors: Stewart Jonathan , Roy Sumon , TRANKLE Cory R , KASIRAJAN Vigneshwar , Rajeev Rahul
Published: June 2023

Background:
Mechanical complications of myocardial infarction (MI), including ventriculoseptal ruptures (VSR) and pseudoaneurysms, are potentially life-threatening events but are less common in the era of timely primary percutaneous coronary interventions. Rare case reports describe MI complicated by VSR requiring repair, with delayed left ventricular (LV) pseudoaneurysm formation from the site of VSR repair. We present an atypical manifestation of one such case.

Case Presentation:
A 55-year-old male was admitted with late presentation inferior MI complicated by inferior VSR, requiring extracorporeal membrane oxygenation and surgical repair. Five months later, he was admitted with left upper extremity weakness and sensory loss. Brain imaging revealed an acute infarct of the precentral gyrus and subacute punctate infarcts of the centrum ovale. He was referred for cardiac magnetic resonance imaging, which revealed a large 6.8x4.9 cm inferior LV pseudoaneurysm containing a large thrombus (Figure 1). He underwent urgent surgery revealing a left ventricular inferior wall defect (Figure 2) and pseudoaneurysm with large mural thrombus. The pseudoaneurysm was successfully repaired via Dacron patch placement and thrombus evacuated.

Conclusion:
Although less common in the modern era, mechanical complications are possible after severe MI. Clinicians should be aware of the potential for atypical manifestations of these complications, including cardioembolic events that can arise within large pseudoaneurysms.
Abstract 12171: Cardiovascular Events in Chimeric Antigen Receptor T-Cell Therapy Recipients With Pre-Existing Cardiac Dysfunction
Authors: Sansoterra Stephen , Rothberg Michael , Riedell Peter , Rehman Mahin , Steingart Richard , Yang Eric H , Gaut Daria , Althaus Thomas , Shouval Roni , Gold Adam , Perales Miguel-Angel , Geyer Mark , Park Jae , Palomba Maria Lia , Feldman Stephanie , Mead Elena , Liu Jennifer , Chen Carol , Gupta Dipti , Yu Anthony , Jang Kristine , Balkan Lauren , Barbar Tarek , Lee Chuy Katherine , Harchandani Bhisham , Horn Evelyn M , Karas Maria G , Sobol Irina , Leonard John , van Besien Koen , Frigault Matthew , Shah Gaurav , Neilan Tomas G , Mahmood Syed S
Published: June 2023

Introduction:
Cytokine release syndrome (CRS) and associated cardiovascular (CV) events are common following infusion of chimeric antigen receptor T cell therapy (CAR-T). There are no data characterizing whether CAR-T recipients with a pre-existing cardiac dysfunction (LVEF <53%) are at increased risk for CV events following CAR-T.

Hypothesis:
We hypothesized that cardiac dysfunction would be associated with a higher rate of CV events following CAR-T infusion. CV events were defined as a composite of cardiogenic shock, clinical heart failure, myocardial infarction, or arrhythmia.

Methods:
Patients in a multi-center registry of adult CAR-T recipients with a known baseline LVEF were included (n=241). Covariates included standard baseline CV and cancer parameters.

Results:
In total, 22 (9%) CAR-T patients had a pre-existing cardiac dysfunction. Those with and without [219 (91%)] baseline cardiac dysfunction were similar in age, gender, pre-existing CV risk factors, and ECOG performance status. LVEF among patients with cardiac dysfunction ranged from 25%-52%. There was no difference in prior anthracycline use, cancer type or burden, but cardiac dysfunction patients had higher rates of prior radiation (36% vs 16%, p=0.02). Cardiac dysfunction patients received less investigational CAR-T (9% vs 31%, p=0.03), more tisagenlecleucel (36% vs 18%, p=0.04), and had similar rates of axicabtagene ciloleucel and lisocabtagene maraleucel. There was no difference in mean CRS grade, rate of ≥2 grade CRS, or in tocilizumab or steroids use between those with and without cardiac dysfunction. During a median follow-up of 294 (IQR 123-661) days, 60 (25%) patients experienced CV events with more events in patients with cardiac dysfunction (63% vs 21%, p<0.001). In a Cox model adjusted for covariates identified in univariate analyses, baseline cardiac dysfunction was independently associated with an increased CV events risk (adjusted HR: 4.9, 95% CI 2.54–9.61, p<0.001)

Conclusions:
CAR-T recipients with pre-existing cardiac dysfunction experience more CV events despite similar rates of CRS.
Abstract 12188: Acute Bi-Ventricular Dysfunction and Cardiogenic Shock Following Transcatheter Mitral Valve Repair
Authors: Azizi Abdul H , Ali Fazal , Marshall Erik , Qureshi Wasif
Published: June 2023

Background:
For patients with functional mitral regurgitation (MR) who remain symptomatic despite GDMT, transcatheter mitral valve repair (TMVR) is emerging as a less-invasive alternatives and can improve symptoms and longevity. We describe a rare case of cardiogenic shock following TMVR.

Case:
63-year-old male with PMHx of CAD with prior CABG, severe MR with EF of 40% developed progressive dyspnea and evaluated for TMVR with a Mitraclip device. TEE pre-deployment confirmed moderate to severe MR (Figure 1). Right heart catheterization revealed preserved cardiac index.

Intraoperative TEE after deployment showed improved MR. Post-procedure, he developed respiratory distress and progressive hypotension requiring vasopressors and inotropes. TTE showed mild MR with severely reduced biventricular function (EF 10%). Cardiac catheterization showed a severely reduced CO/CI 3.1/1.42. Mechanical circulatory support was initiated with Impella CP due to persistent cardiogenic shock. By POD 3, he was off all inotropes and MCS was discontinued. His EF recovered to 45% during a 3- month visit.

Decision Making:
Causes of cardiogenic shock post mitral valve procedure include cardiac tamponade, acute mitral stenosis, intrathoracic hemorrhage and afterload mismatch. Afterload mismatch is due to reduction in left ventricular stroke volume when preload is not compensated for an acute increase in afterload. It is a known complication after mitral valve surgery; however it is rarely seen post TMVR. This patient likely experienced afterload mismatch after his mitral clipping procedure as evidenced by the acute, transient decline in LVEF (55% to 10%).

Conclusion:
Afterload mismatch is a rare phenomenon that can cause cardiogenic shock post percutaneous mitral repair procedures. It must be rapidly addressed with inotropic and/or mechanical support to prevent permanent end organ dysfunction and circulatory collapse. Prompt treatment allows for excellent recovery.
Abstract 12196: Effect of Metformin on Heart Failure in Patients With Diabetes Mellitus Receiving Anthracycline Chemotherapy
Authors: Onoue Takeshi , Kang Yu , Lefebvre Bénédicte , Smith Amanda M , Denduluri Srinivas , Scherrer-Crosbie Marielle
Published: June 2023

Introduction:
The prevention of heart failure (HF) is an essential issue in patients treated with anthracyclines, however, existing treatments have demonstrated modest effects. Metformin (MET), widely used to treat diabetes, protects from anthracyclines-induced cardiotoxicity in vitro and in murine models. However, there is no research investigating the cardioprotective effects of MET in patients treated with anthracyclines.

Hypothesis:
MET is cardioprotective in patients treated with anthracyclines.

Methods:
Out of 5655 patients undergoing new anthracyclines therapy at a tertiary center between 2008-2021, 260 patients were treated with MET. The clinical characteristics associated with the use of MET were identified and a propensity-score (gender, diabetes, type of cancer, kidney and cerebrovascular disease) used to match 200 patients treated with MET to 200 patients without MET. The primary outcome was new-onset symptomatic HF defined by the AHA/ACC guidelines occurring within 1 year of the initiation of anthracyclines. Proportional hazard analysis was used to identify characteristics associated with HF.

Results:
Patients were 65 years old [57-70], 34% male. No differences were noted in age, cardiovascular risk factors, history, use of beta-blockers and ACE inhibitors between the MET and non MET groups. Six patients (3%) treated with MET and 20 matched patients (10%) developed HF within 1 year of anthracyclines initiation (P=0.004, Figure). Use of MET ([HR]: 0.27; 95% CI: 0.1 to 0.64; p = 0.002), use of insulin (HR: 2.27; 95% CI: 1.05 to 5; p = 0.04), coronary artery disease (HR: 4.69; 95% CI: 2.06 to 10.2; p < 0.001), and chronic kidney disease (HR: 2.65; 95% CI: 1.21 to 5.77 p = 0.02) were associated with incident HF.

Conclusions:
MET significantly reduced the risk for HF in patients treated with anthracyclines. Our findings are consistent with previous
experimental
studies and suggest a new therapeutic option in the prevention of cardiotoxicity.
Abstract 12203: Safety and Effectiveness of Pre-Procedure Imaging for Percutaneous Left Atrial Appendage Occlusion: Insights From the National Cardiovascular Data Registry (NCDR) LAAO Registry
Authors: Clarke John-Ross D , Higgins Angela Y , Wang Yongfei , Faridi Kamil , Curtis Jeptha P , Freeman James V , Friedman Daniel
Published: June 2023

Introduction:
Pre-procedure cardiac computed tomography (CT) or magnetic resonance imaging (MRI) prior to percutaneous left atrial appendage occlusion (LAAO) has many theoretical benefits but data on its association with periprocedural safety and effectiveness is limited.

Hypothesis:
Pre-procedure imaging has the potential to improve the safety and effectiveness of LAAO.

Methods:
We evaluated patients in the NCDR LAAO Registry who underwent LAAO between 1/2016 and 6/2021 to compare the safety and effectiveness of LAAO procedures by use vs. non-use of pre-procedural CT/MRI. Study outcomes included implant success (deployment and release of device), device success (device released with peri-device leak <5mm), and procedure success [device released with peri-device leak <5mm and no in-hospital MAE (major adverse effects)]. Multivariable logistic regression was used to assess the relationship between pre-procedure imaging and outcomes.

Results:
Pre-procedure CT/MRI was used for 18.2% (n=20,851) of the 114,384 procedures in this study and significant variability was noted by hospital (
Figure
). CT/MRI use was more common among government and university hospitals, larger hospitals, non-teaching hospitals, and hospitals in the Midwest and south, and was less common among patients with uncontrolled hypertension, abnormal renal function, and no prior thromboembolism. Overall rates of implant success, device success, and procedure success were 93.4%, 91.2%, and 89.4%. Pre-procedure CT/MRI was independently associated with an increased likelihood of implant success (OR 1.08, CI 1.00-1.17), device success (OR 1.10, CI 1.04-1.16), and procedural success (OR 1.07, CI 1.02-1.13) There was no significant difference in risk for MAE (OR 1.02, 0.92-1.12).

Conclusions:
Pre-procedure CT/MRI was used 1 in 5 LAAO procedures and was independently associated with higher likelihood of implant success, device success, and procedure success, but no difference in MAE.
Abstract 12239: Objectively Measured Physical Activity Decreases the Risk of Subclinical Cardiovascular Disease: A Systematic Review
Authors: Narendrula Aparna , Brinza Ellen , Horvat Davey Christine , Webel Allison R , Longenecker Chris T
Published: June 2023

Introduction:
Physical activity (PA) decreases the risk of cardiovascular events, but to what degree this is related to effects on surrogate markers of subclinical cardiovascular disease (CVD) is unclear. Clarifying the relationship between objectively measured PA and subclinical CVD would provide justification for using measures of subclinical CVD in clinical trials of PA interventions.

Hypothesis:
We hypothesized that higher levels of objectively measured PA are associated with less subclinical CVD.

Methods:
We performed a systematic review using Medline, Embase, CINAHL and Cochrane (January 1, 2000 - January 12, 2022). Studies of adult populations that examined the relationship between objectively measured PA (accelerometry) and subclinical CVD were included. Markers for subclinical CVD included: ankle brachial index (
n
=4 studies); arterial stiffness (
n
=31); carotid artery plaque/stenosis and intima media thickness (
n
=9); coronary artery atherosclerosis (
n
=4); endothelial function (
n
=8); measures of cardiac structure and function (
n
=4); and eight studies included multiple of the aforementioned outcomes. For those studies, we considered results on each outcome separately. Risk of bias was also assessed.

Results:
PA was inversely associated with subclinical CVD in 60 of 78 included analyses (76.9%). Of these, five studies (6.4%) found only an association with higher levels of PA. In six studies (7.7%), PA was no longer associated with subclinical CVD after adjustment for confounders. Seven analyses (9.0%) demonstrated mixed results but demonstrated an inverse relationship between PA and subclinical CVD in specific circumstances. Only 18 studies (23.1%) suggested that PA was not associated with decreased subclinical CVD.

Conclusions:
Increased PA is associated with less subclinical CVD across diverse populations. Interventions to increase PA have the potential to reduce the burden of subclinical CVD and, therefore, clinical CVD events.
Abstract 12259: Recurrent Coronary Artery Dissection in Patient With Systemic Medium-Sized Vessel Vasculitis
Authors: MURPHY MICHAEL D , Fitzgibbons Timothy
Published: June 2023

Introduction:
Universal definition of myocardial infarction (MI) categorizes spontaneous coronary artery dissection (SCAD) as Type 2 ischemia from non-atherothrombotic obstruction. SCAD is rare but growing evidence suggests it is more common than previously understood. Overlap in clinical presentation with Type 1 MI makes invasive coronary angiography (ICA) the gold standard for diagnosis. Here we present a patient with polyarteritis nodosa (PAN) and the sequelae of coronary artery aneurysms and dissections visualized by ICA and further characterized by noninvasive coronary computed tomography angiography (CCTA).

Case Report:
A 37-year-old man with smoking and hypertension history presented with acute chest pain that felt similar to when he was diagnosed with SCAD of the first diagonal branch one year prior by ICA. Workup then included elevated inflammatory markers and further imaging demonstrating ectatic and beaded-appearing major intra-abdominal and vertebral arteries consistent with PAN. He completed outpatient cyclophosphamide and continued on chronic oral steroids.The catheterization lab was activated on this presentation for ST segment elevations on initial ECG concerning for an inferior MI. Here the distal branches of the right coronary artery (RCA) had new aneurysms and long stenoses with severe luminal narrowing and intramural hematoma consistent with Type 2 SCAD. The culprit lesions had normal TIMI grade 3 flow so were not revascularized. CCTA further characterized the filling defect and RCA false lumen as Type 1 SCAD. Echocardiogram demonstrated a new wall motion dysfunction in correlative distribution. He was optimized on medical therapy including continued dual antiplatelet agents and steroids.

Discussion:
This patient’s case lends itself to the hypothesis that his PAN manifested ectatic changes to the coronary vasculature from inflammation that predisposed him to recurrent dissection. Therefore, it is reasonable to initiate a vasculitis workup following discovery of coronary artery ectasia and/or dissection. CCTA may even be an effective tool for diagnosis and surveillance of such disease in the right patient and as a means to avoid invasive testing risks.
Abstract 12260: The SMARTER Trial: Is Engagement With Mhealth Better With Daily Feedback to Self-Monitoring Compared to No Feedback?
Authors: Burke Lora E , Conroy Molly B , Bizhanova Zhadyra , Kariuki Jacob K , Cheng Jessica , Beatrice Britney , Sereika Susan M
Published: June 2023

Introduction:
Self-monitoring (SM) is the cornerstone of behavior change for weight loss as is providing feedback (FB) to SM. FB to SM can be delivered remotely and in real time.

Hypothesis:
Participants assigned to SM+FB will show greater engagement in the weight loss intervention, as measured by adherence to dietary goals, than the SM group.

Methods:
SMARTER was a 2-arm trial that randomized 502 adults aged ≥18 years with a body mass index (BMI) 27-43 kg/m
2
to 1) self-monitoring of diet and physical activity with up to 3 daily FB messages (SM+FB: n=251) or 2) self-monitoring only (SM: n=251). Daily calorie goals were based on baseline body weight and gender; the fat goal was 25% of caloric intake. Monthly adherence to calorie and fat goals were defined as number of days with intake within 85% -115% of daily goals divided by number of valid days (≥15 days with ≥50% of daily goals recorded) multiplied by 100%. Linear mixed modeling with random intercept and slope was used to examine the effect of treatment assignment on adherence over 12 months.

Results:
Participants were predominantly female (79%) and White (83%) with a mean age of 45±14.4 years and a mean BMI of 33.7±3.96 kg/m
2
. Monthly percentages of days adherent to calorie goal (b [95% CI]: -2.07 [-3.58, -0.56], b^2: 0.34 [0.08, 0.59], b^3: -0.02 [-0.03, -0.01],
all P<.05
) and fat goal (b: 2.14 [1.03, 3.25], b^2: -0.31 [-0.50, -0.12], b^3: 0.01 [0.003, 0.02],
all P<.05
) decreased curvilinearly over time. On average, SM+FB had greater monthly percentages of days adherent to calorie goal (4.42 [0.41, 8.45],
P=.03
) and fat goal (3.90 [1.44, 6.36],
P<.05
) than SM. Moreover, the rate of decline in monthly percentages of days adherent to calorie (b: -1.98 [-3.03, -0.93], b^2: -0.14 [0.06, 0.22],
all P<.05
) and fat (b: -1.18 [1.94, -0.42], b^2: 0.10 [0.04, 0.16],
all P<.05
) goals were non-linear but different between groups.

Conclusions:
Personalized FB messages were effective in promoting adherence to dietary goals; however, overall engagement with the intervention was low, which may explain small between group differences.
Abstract 12279: Cardiovascular Disease Progression in Children With Homozygous Familial Hypercholesterolemia Despite Early Diagnosis on a Genetic Cascade Screening Program
Authors: Juliani Fabiana C , Chacra Ana Paula M , Miname Marcio H , Salgado Filho Wilson , Mizuta Marjorie H , Jannes Cinthia E , Krieger Jose E , Maranhao Raul C , Santos Raul D , Rocha Viviane Z
Published: June 2023

Introduction:
Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extremely elevated low-density lipoprotein cholesterol (LDL-c) and very high risk of premature atherosclerotic cardiovascular (ASCVD) and aortic/supraortic valve heart diseases (VHD). The study aim was to examine clinical and biochemical trajectories of a cohort of HoFH patients since childhood.

Methods:
In this longitudinal study we assessed the incidence of manifest or subclinical ASCVD (coronary or carotid) and VHD as well as plasma lipids in a cohort of HoFH subjects during a 12.9 ± 9.6 years follow-up.

Results:
From the 868 individuals ≤19 y-old (at baseline) that were genotyped on a genetic cascade screening program, 420 (48.4%) had an FH mutation. From children bearing mutations, 12 were true homozygotes and 1 was compound heterozygote (53.8% females, mean age 7.5 ± 4.1 years at the first visit). During follow-up all were on statin and ezetimibe therapies, and the mean final dose of atorvastatin was 56 ± 27 mg/d (n=10); and rosuvastatin, 26 ± 17 mg/d (n=3). Initial and on treatment LDL-c were 655 ± 177 mg/dL and 399 ± 150 mg/dL, respectively, with a mean 39.1% reduction (-256 mg/dL). None were under LDL apheresis; 2 patients used mipomersen, 2 lomitapide, and 2 are currently using PCSK9 inhibitors. Subclinical cardiovascular disease, either coronary, carotid or in aortic valve, was identified in 38.5% (n=5; mean age 16.4 ± 9.8 years), whereas 30.8% had a clinical cardiovascular event (n=4; mean age 22.8 ± 6.8 years), with 2 deaths. Therefore, 69.3% had either subclinical or manifest cardiovascular disease.

Conclusion:
Despite early diagnosis and LDL-c reduction HoFH is still marked by an adverse and premature cardiovascular disease progression. Conventional lipid lowering therapies are not adequate to prevent ASCVD and VHD disease course.
Abstract 12285: Low Risk of Stroke From Endocardial Ventricular Arrhythmia Ablation
Authors: Hasegawa Kanae , Yoneda Zachary T , Tokutake Kenichi , Richardson Travis D , Jay Montgomery A , Shen Sharon T , Estrada JC , Saavedra Pablo J , Emerson Amy , Walker Marilyn L , Michaud Gregory F , KANAGASUNDRAM Arvindh N , Stevenson William G
Published: June 2023

Background:
Recent studies increase concern for embolic events during radiofrequency ablation (RFA) for ventricular arrhythmias (VA).

Objective:
To assess peri-procedural symptomatic embolic events and anticoagulation regimens in patients undergoing endocardial RFA for VA.

Methods:
All patients undergoing endocardial RFA for VA from October 2018 to September 2021 were prospectively assessed for complications in hospital before discharge and at 30 days by clinic visit or phone call. Anticoagulation regimens were at the discretion of the treating physician.

Results:
There were 663 procedures in 616 patients (age 62
+
4 yrs, 73% structural heart disease, 48% sustained VT). Prior to the procedure 464 patients (70%) were taking an antithrombotic agent, either a direct acting anticoagulant agent (DOAC), warfarin, aspirin (ASA), other antiplatelet agent, or combinations (table 1); and the same type of agent was continued after ablation in 462. Of the 199 patients not receiving antithrombotic agents pre-ablation, 82.4% received 325 mg of ASA daily after the procedure, 3.0% received lower dose ASA, and 16 were started on DOAC or warfarin. There were 59 complications (8.9%) in 53 procedures. There were 2 strokes (0.3%); there were no transient ischemic attacks or other embolic events. There were 25 (3.8%) bleeding complications including 14 due to vascular access (2.1%) and 11 pericardial effusions (1.6%). Bleeding complications were more frequent in patients on the combination of antiplatelet and DOAC pre- or post-procedure.

Conclusions:
In this large single center series most patients undergoing VA ablation were receiving antithrombotic therapy pre-procedure that was continued post procedure. Full dose ASA was the most common post-procedure regimen for those not on pre-procedure anticoagulation. Stroke and emboli appear very rare. Combined antiplatelet and DOAC therapy is associated with increased bleeding risk.
Abstract 12290: Effects of Hemodynamic Triggers and Genetic Predisposition on Endocardial Fibroelastosis Recurrence
Authors: Diaz-Gil Daniel , Silva-Gomez Natalia , Morton Sarah U , Seidman Jonathan G , Zurakowski David , Staffa Steven , Piekarski Breanna L , Marx Gerald R , Emani Sitaram , Del Nido Pedro J , Friehs Ingeborg
Published: June 2023

Introduction:
Endocardial fibroelastosis (EFE) can be the cause of diastolic dysfunction in congenital heart defects. It is derived through endothelial-to-mesenchymal transformation (EndMT), and flow disturbances have been associated with its development. Surgical resection is the only available treatment, but recurrence is often observed. We sought to determine hemodynamic predictors and genetic predisposition of EFE recurrence for preoperative risk stratification.

Methods:
In 93 patients undergoing LV-EFE resection from 01/2010-03/2021, univariate and multivariable competing risks analysis was applied to determine the effects of hemodynamic parameters on EFE recurrence. In 48 patients with EFE, we classified patient’s rare
de novo
, damaging missense, and loss of function variants from whole exome sequencing through gene ontology and pathway network enrichments analysis associated with EndMT and/or reduced myocardial contraction or conduction.

Results:
51 patients (54.8%) had EFE recurrence with a median time to recurrence of 2.2 years (95% CI 1.3-3.0). We identified mitral valve area (<1 cm
2
), LV filling pressures (≥9 mmHg), aortic valve (AoV) mean systolic gradient (≥25 mmHg), and AoV diameter (Z-score ≤ -1.6) as predictors of faster time to recurrence (Fig. 1A). In a scoring system, these predictors together achieved an area under the curve of 0.79. Rare variants in the cohort were found in genes enriched for functions related to EndMT and myocardial conduction/contraction, with 75% of patients possessing a variant in such a gene. The combination of both (n=16) was associated with a significantly higher yearly recurrence incidence (p<0.05, Fig. 1B).

Conclusions:
The degree of hemodynamic disturbances and genetic predisposition predict the time to recurrence in patients after EFE resection. Understanding mechanisms behind EFE progression might provide an opportunity to prevent recurrence and develop new treatment options.
Abstract 12291: Natriuretic Peptide Levels and Predicting Risk of Developing New Diabetes Mellitus or Metabolic Syndrome: A Population Based Study
Authors: Marjara Jasraj S , Adel Fadi W , Scott Christopher , Chen Horng
Published: June 2023

Introduction:
The prevalence of metabolic syndrome (MS), and diabetes mellitus (DM) is increasing, and the use of biomarkers to identify subjects at risk of developing MS or DM may be useful for disease prevention. Natriuretic peptides (NPs) are well known for their role as biomarkers in heart failure (HF), but are increasingly being recognized for their favorable metabolic actions and potential role as risk modifiers for the development of DM and MS. To date, however, this risk relationship has not been well defined in the general population.

Hypothesis:
Adults in the general population with lower NP levels are at higher risk for developing DM or MS.

Methods:
A retrospective review of the Olmsted County Heart Function Study cohort, a population-based random sample of 2042 Olmsted County, MN residents aged ≥ 45 years. A subgroup of community-dwelling subjects without MS or DM at Visit 1 was identified and subjects returned for followup after 4 years (Visit 2). We compared the characteristics of subjects that developed MS or DM after 4 years to those that did not.

Results:
Of the 911 subjects who did not have MS or DM at visit 1, 93 (10.2%) developed either MS or DM at visit 2. Subjects who developed MS or DM at visit 2 were more likely to have higher baseline BMI (p <0.001), lower HDL (p<0.001), higher triglycerides (p < 0.001), higher insulin (p< 0.001), higher aldosterone (p < 0.001) levels, lower NT-proANP (p<0.001) and lower NT-proBNP levels (p < 0.01) compared to those that did not develop MS or DM. Those that developed MS or DM were also at higher risk for development of HF when controlling for age and sex (HR 2.73 CI 1.25-5.96). On univariate analysis, higher baseline levels of NT-proANP and NT pro-BNP had a significant negative association with developing new MS or DM (ORs per 1 SD increase: 0.64, CI 0.51-0.79 p < 0.0001 and 0.76, CI 0.62-0.95 p=0.016, respectively).

Conclusions:
Among adults aged ≥ 45 years in the community, low levels of NT- ANP and NT-proBNP are associated with increased risk of development of DM and MS. Further studies are warranted to determine if potentiating the natriuretic peptide system would delay the development of DM or MS.
Abstract 123: Bystander Cpr Usage In Out-of-hospital Cardiac Arrest During The Covid-19 Pandemic: Results From The Northeast Georgia Cardiac Arrest Registry
Authors: Mahmood Riaz , Asreb Abdullah , Ahn Joon
Published: June 2023

Background:
During the COVID-19 pandemic, a higher incidence of out-of-hospital cardiac arrest (OHCA) has been reported but rates of bystander CPR usage have not been studied. Due to the COVID-19 pandemic, bystanders may be reluctant to perform CPR due to risk of infection and due to social isolation measures, there may be less bystanders present to perform CPR.Objective: The purpose of the study was to study rates of bystander CPR usage in out-of hospital cardiac arrest (OHCA) during the COVID-19 pandemic and to evaluate for any association between bystander CPR usage and increasing COVID-19 infection during 2020 and 2021.

Methods:
We performed a retrospective study of the Northeast Georgia Cardiac Arrest Registry to compare bystander CPR usage for all patients presenting to Northeast Georgia Medical Center in Gainesville, Georgia with OHCA from 14 surrounding counties of northeast Georgia from March 2019 to December 2021.

Results:
A total of 18,421 and 18,678 COVID-19 infections were reported in Hall County between Mar-Dec 2020 and Jan-Dec 2021, respectively. A total of 228 cardiac arrests occurred in 2019, 273 in 2020, and 268 in 2021. Overall bystander CPR usage was 44% in 2019, 43% in 2020, and 47% in 2021, p = .64. Before COVID-19 the bystander CPR usage was 43% and 46% during, p = 0.44. There was no significant correlation between bystander CPR usage and COVID-19 infections in Hall County (r = 0.06, p = 0.79). Multivariable logistic regression model demonstrated that initial shockable rhythm (p < 0. 001) was the strongest predicator of bystander CPR (table 1).

Conclusions:
Bystander CPR usage in OHCA in the northeast Georgia region remained constant despite the COVID-19 pandemic. There were no significant differences in bystander CPR usage in OHCA prior to or during COVID-19 pandemic. Additional studies are needed to evaluate for possible variables which may be contributing to initial shockable rhythm as the strongest predicator of bystander CPR.
Abstract 12308: Presenilin-2 Regulates Mitophagy via Promoting Intracellular Translocation of Parkin to Mitochondria
Authors: Saito Tsunenori , Kodani Eitaro , Gottlieb Roberta A
Published: June 2023

Introduction:
Presenilin-2 (PS2) is a component of the γ-secretase complex, intracellular protease. Variant in
PSEN2
, the causative genes of Alzheimer's disease, are also implicated in the development of dilated cardiomyopathy. Hypoxia increases
PSEN2
expression 10-fold over normal, and
PSEN2
knockout (PS2KO) cells exhibit significantly lower ATP production. However, the mechanism of the mitochondrial dysfunction has not been fully elucidated.

Hypothesis:
PS2 regulates mitochondrial selective autophagy (mitophagy) by promoting the translocation of Parkin to mitochondria.

Methods:
Expression of autophagy and mitophagy markers was examined using cultured rat cardiomyocytes (H9c2) silenced for
PSEN2
and
PSEN1
, exposed to 10 μM carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP), a mitochondrial uncoupler used to induce mitophagy.

Results:
Mitochondrial respiration of PS2KO-H9c2 was showed reduced (maximal respiration capacity, 68.4 ± 27.0 pmol/min/cells) compared to PS1KO-H9c2 (147.6 ± 27.2 pmol/min/cells) or normal cells (276.6 ± 11.9 pmol/min/cells) (P<0.001). When mitophagy-dye modified with perylene-3,4-dicarboxylic anhydride was used, mitophagy detection rates were significantly increased by the addition of FCCP to normal H9c2 (34% increased, P=0.041) and PS1KO-H9c2 (46% increased, P=0.035), but there was no change with PS2KO-H9c2 (25% decreased, P=0.232). When FCCP was added to PS2KO-H9c2, Parkin was not only enhanced in whole cell lysate of PS2KO-H9c2, but also increased even at mRNA level; however, in the isolated mitochondrial fraction, Parkin was significantly reduced, and PINK1 and phosphorylated ubiquitin (serine 65) were also attenuated. In Immunofluorescent staining confirmed that Parkin was not co-localized with mitochondria in PS2KO-H9c2, implicating PS2 in promoting the transfer of Parkin from the cytoplasm to mitochondria. As mitochondrial depolarization causes PINK1 stabilization needed for Parkin recruitment, we interrogated mitochondrial membrane potential measurement using Rhodamine-123 and examined expression of OPA1 isoforms; no significant results were obtained.

Conclusions:
PS2 contributes to the intracellular transport of Parkin to regulate mitophagy.