bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14495: Clinical Outcomes of Transcatheter Aortic Valve Replacement for De Novo Aortic Valve Insufficiency After Left Ventricular Assist Device Implantation
Authors: Koda Yojiro , Nishida Hidefumi , Nguyen Ann , Kalantari Sara , Chung Bow , Kim Gene H , Sarswat Nitasha , Smith Bryan , Grinstein Jonathan , Onsager David , Song Tae , Jeevanandam Valluvan , Ota Takeyoshi
Published: May 2021

Objective:
This study aimed to assess clinical outcomes of transcatheter aortic valve replacement (TAVR) for de novo aortic valve insufficiency (AI) after left ventricular assist device (LVAD) implantation.

Methods:
We defined de novo AI as a new-onset moderate AI or greater after the index LVAD implantation. Survival rate in patients with de novo AI was compared with ones without de novo AI, and clinical outcomes of TAVR in the patients with de novo AI were assessed.

Results:
Between 7.2008 - 1.2020, a total of 513 patients underwent LVAD implantation. Among them, 460 patients who had postoperative cardiac echography data available were included in this study. Sixty one patients (13%) developed de novo AI (dAI group) and 399 patients (87%) were not (non-dAI group). Overall survival in the dAI group was significantly lower than that in the non-dAI group (at 1 year: 54±7 vs. 73±2%, at 3 years: 30±8 vs. 51±3%,Log-Rank P=0.0004). In the dAI group, seven patients underwent TAVR for severe de novo AI of the native AVs. Calcification in the AVs measured by preoperative computed tomography (CT) was non-calcification in 4 patients, mild in 1 patient, and moderate in 2 patients. Based on measurements from CT, Valsalva sinus was 35 [32,36]mm (median[25%tile,75%tile]). All TAVR procedures were performed via a femoral artery approach. Sapien3 was implanted in 4 patients (23mm (N=1), 26mm (N=1), 29mm (N=2)). CoreValve was implanted in 3 patients (31mm (N=1), 31mmх2 (N=1), 34mm (N=1)). As an intraoperative complication, CoreValve migrated into the left ventricle in 1 patient. The degrees of postoperative residual AI were none or trace in 5 patients who were discharged in a good condition, and severe (perivalvular leakage (PVL)) in 2 patients who died during the admission. The 2 patients, who had severe postoperative PVL, did not have calcification in the AVs. Overall survival at 1 year in the 5 patients, who were discharged alive, was 100%, and freedom from moderate or greater AI was 100% at 6 months and 60% at 1 year.

Conclusions:
De novo AI negatively affected the survival rate in LVAD patients. TAVR treatment for de novo AI in LVAD patients might be a reasonable option. However, careful patient selection would be necessary.
Abstract 14498: MRI: Additive Value for the PM/ICD Device Patient; A Safety and Efficacy Study
Authors: Biederman Robert W , Gevenosky Loretta , Samar Huma , WILLIAMS RONALD , Lombardi Richard , Shah Moneal , Mangini Francesco , Farah Victor , Bonnet Christopher , Doyle Mark
Published: May 2021

Introduction:
While many studies have unequivocally demonstrated MRI safety in pts with thoracic devices, the clinical value is rarely considered. Yet, recent CMS-NCD supports more widespread considerations providing a unique opportunity for improved care.

Hypothesis:
We propose that MRI in pts with PM/ICDs are crucial to existing diagnosis and often substantially alters diagnosis and subsequent care.

Methods:
An evaluation of 1145 PM/ICDs pts who underwent MRI (GE 1.5T,WI) over 12 yrs (95% <5yrs) was performed. The devices consisted of 665 PMs, 418 ICDs, 30 retained leads and 18 Loop/Linqs (some pts >1). Specific criteria were followed to objectively determine if MRI diagnosis altered pt care. Accordingly, 4 Boolean Logic Construct questions were posed within 1 week of MRI by technologist/MD: 1) Did primary diagnosis change? 2) Did MRI provide additional diagnoses? 3) Was pre-MRI (tentative) diagnosis confirmed? 4) Did pt care change? If 'Yes' was answered to any question, MRI was considered of value to pt diagnosis and/or impending therapy.

Result:
Avg MRI: 34±21min. In 1145 pts: 819 (72%) were neuro/neurosurgery (NS), 110 (10%) were musculoskeletal (MK) and 216 (19%) were cardiac (CV) pts. On review, NS-MRI's, 669 (87%) provided additional information. The diagnoses changed in 553 (73%) and medical therapy changed in 536 (70%). In only 73(10%) did MRI simply confirm original diagnosis. In 216 CV cases, MRI provided additional data. In 178 pts (82%), MRI changed the original diagnosis and in 138 (64%), pt care. MRI was uninterpretable in 29 (11%; ICD artifact) while in 41 (19%) pts there was no diagnostic change. In essence, 174 (81%) of the CV cases benefited by MRI. Finally, in 110 MK cases, MRI provided additional data in 103 (96%), in 95 (88%) changed pt care and in 1 pt simply confirmed the diagnosis. Importantly, with careful attention to device reprogramming and scanner sequences, no safety/device issues occured.

Conclusion:
In 1145 pts with devices, MRI adds substantial clinical value to diagnosis and subsequent management justifying any residual risk. We believe, this is the largest study to focus solely on diagnostic value and efficacy under the assumption that safety can be routinely accomplished; a new paradigm in the error of a generation of non-CIED devices.
Abstract 14499: Impact of Pre-existing and New Incident Atrial Fibrillation on Outcomes of Patients With Acute Pulmonary Embolism: Findings From an International Registry
Authors: Bikdeli Behnood , Jimenez David , Del Toro Jorg , Piazza Gregory , Rivas Augussina , Fernández-Reyes José Luis , Sampériz Ángel , Otero Remedios , Suriñach José María , Siniscalchi Carmine , Martín-Guerra Javier Miguel , Castro Joaquín , Muriel Alfonso , Lip Gregory , Goldhaber Samuel Z , Monreal Manuel
Published: May 2021

Background:
Atrial fibrillation (AF) may occur prior to or early in the course of acute pulmonary embolism (PE). The impact of AF on outcomes of patients with PE remains uncertain.

Methods:
Using the data from a large prospective multicenter registry of patients with objectively-confirmed PE (04/2014 to 01/2020), we identified three patient groups: 1) those with pre-existing AF 2) patients with newly identified AF within 2 days from the index PE (incident AF) and 3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, in unadjusted and multivariable adjusted models considering those without AF as referent.

Results:
Among 16,497 patients with PE, 792 had pre-existing AF. Compared with those without AF, patients with pre-existing AF, had increased odds of 90-day all-cause (Odds ratio [OR]: 2.81 (95% confidence interval [CI]: 2.33-3.38) and PE-related mortality (OR: 2.38, 95% CI: 1.37-4.14). After multivariable adjustment, pre-existing AF significantly increased the odds of all-cause mortality (OR: 1.91, 95% CI: 1.57-2.32) but not PE-related mortality (OR: 1.50; 95% CI: 0.85-2.66). Pre-existing AF was associated with increased hazard for ischemic stroke at 1-year follow-up (hazard ratio [HR]: 5.48; 95% CI: 3.10-9.69). Among 16,497 patients with PE, 445 developed incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR: 2.28; 95% CI: 1.75-2.97) and PE-related (OR: 3.64; 95% CI: 2.01-6.59) mortality. Findings were similar in multivariable analyses and at 1-year follow-up (Figure). No patients with incident AF developed ischemic stroke.

Conclusion:
In patients with acute symptomatic PE, both pre-existing AF and incident AF predict an adverse clinical course, although the type of adverse outcomes may be different depending on the timing of AF onset.
Abstract 14623: Phase Angle as an Indicator of Sarcopenia, Undernutrition, and Cachexia in Inpatients With Cardiovascular Diseases
Authors: Hirose Suguru , Nakajima Toshiaki , Haruyama Akiko , Yasuda Tomohiro , Yamaguchi Suomi , Toyoda Shigeru , Shibasaki Ikuko , Fukuda Hirotsugu , Inoue Teruo
Published: May 2021

Introduction:
In patients with heart failure, malnutrition is often associated with sarcopenia, and cachexia, closely related to the prognosis of the disease. Phase angle(PA) is an angle that expresses the resistance of the cell membrane, and is related to the health of the cell and the nutritional state of the cell membrane. It is attracting attention as a prognostic factor and nutritional index for various diseases. We investigated the clinical usefulness of PA as markers of sarcopenia, cachexia and malnutrition in hospitalized patients with cardiovascular disease.

Methods:
Total 412 patients(277 males and 135 females) who underwent cardiac rehabilitation on admission due to cardiovascular diseases were included in this study. We performed body composition analysis(Inbody S10) such as PA, and skeletal muscle mass index(SMI). The nutritional states were evaluated by BMI, CONUT score, blood albumin level(Alb), and Hb. The blood concentration of BNP and eGFR were also measured. Sarcopenia was judged by the AWGS algorithm, and cachexia was judged by using BMI<20 and serum parameters of Alb, Hb, and CRP.

Results:
Both SMI and PA negatively correlated with age, and positively correlated with BMI, grip strength, knee extension strength, and SPPB score in both sexes. SMI and PA were also significantly associated with CONUT score, Hb, and Alb in males, but PA was more strongly associated with these nutritional aspects. In females, PA was correlated with Hb and Alb, but not with SMI. Sarcopenia was found in 31.6% of men and 32.4% of women. The cut-off values of PA obtained from the ROC curve in patients with sarcopenia were 4.55°for males and 4.25°for females. The cut-off values for PA in ROC curves for those with cachexia were 4.15°for males and 4.25°for females. When grip strength, knee extension strength, CRP, BNP, eGFR, Hb, and Alb were independent factors, multiple regression analysis showed that grip strength and BNP were the independent determinants of SMI, whereas grip strength, BNP, and Hb were the independent determinants of PA, after adjusting for age and BMI in males.

Conclusions:
This study provides the evidence showing that PA can be highly useful as a marker for sarcopenia, malnutrition and then cachexia in hospitalized patients with cardiovascular disease.
Abstract 14648: Gender Differences in Procedural Complications Associated With Atrial Fibrillation Catheter Ablation: A Systematic Review and Meta-analysis of 244,353 Patients
Authors: Campbell Martin L , Larson John , Farid Talha , Westerman Stacy , Lloyd Michael S , Shah Anand D , Leon Angel R , El-Chami Mikhael F , Merchant Faisal
Published: May 2021

Introduction:
Women undergoing atrial fibrillation catheter ablation (AFCA) have higher rates of vascular complications and major bleeding. However, studies have been underpowered to detect differences in rare complications such as stroke/transient ischemic attack (TIA) and procedural mortality.

Methods:
We performed a systematic review of databases (PubMed, World of Science, Embase) to identify studies published since 2010 reporting AFCA complications by gender. Six complications of interest were: 1) vascular/groin complications; 2) pericardial effusion/tamponade; 3) stroke/TIA; 4) permanent phrenic nerve injury; 5) major bleeding & 6) procedural mortality. For meta-analysis, random effects models were used when heterogeneity between studies was ≥ 50% (vascular complications, major bleeding) and fixed effects models for other endpoints.

Results:
Of 5716 citations, 19 studies met inclusion criteria, comprising 244,353 patients undergoing AFCA, of whom 33% were women. Women were older (65.3 ± 11.2 vs. 60.4 ± 13.2 years), more likely hypertensive (60.6 vs. 55.5%) and diabetic (18.3 vs. 16.5%) and had higher CHA
2
DS
2
-VASc scores (3.0 ± 1.8 vs. 1.4 ± 1.4) (p<0.0001 for all comparisons). The rates of all 6 complications were significantly higher in women (Table). However, despite statistically significant differences, the overall incidences of major complications were very low in both genders: stroke/TIA (women 0.51 vs. men 0.39%) and procedural mortality (women 0.25 vs. men 0.18%).

Conclusion:
Women experience significantly higher rates of AFCA complications. However, the incidence of major procedural complications is very low in both genders. The higher rate of complications in women may be partially attributable to older age and a higher prevalence of comorbidities at the time of ablation. More detailed studies are needed to better define the mechanisms of increased risk in women and to identify strategies for closing the gender gap.
Abstract 14661: High Sensitive Troponin Elevation Pattern in Covid-19 Era
Authors: Maino Alessandro , Di Stasio Enrico , Grimaldi Maria Chiara , Cappannoli Luigi , Rocco Erica , Biscetti Federico , Raffaele Landolfi , Biasucci Luigi M
Published: May 2021

Introduction:
Coronavirus disease 2019 (COVID-19) is a pandemic disease that has caused a public health emergency due to its high rapid spread, to the high mortality rate, and the high percentage of patients requiring hospitalization and intensive care . Information regarding the impact of cardiovascular complication on fatal outcome is scarce.

Purpose:
To compare the levels of hs-Tn between patients affected by SARS-CoV-2 admitted to our hospital in the period February 20-April 9, 2020 versus the general population COVID free. Furthermore, we studied the dependence of hs-Tn levels in SARS-CoV-2 patients on disease severity and on other epidemiological, clinical and laboratory parameters.

Methods:
This retrospective single-center study analyzed all patients in whom hs-TnI was determined at the Policlinico A.Gemelli (Rome, Italy) from 20 February 2020 to 09 April 2020. One hundred-seventy of these patients received SARS-CoV-2 diagnosis. Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with COVID 19.

Results:
In our study, the population affected by SARS-CoV-2 (n=170) showed a significant association between disease severity and troponin levels (median [range] = 4.0 [<2.4-227.0], 13.5 [<2.4-545.0] and 34.0 [<2.4-45345.0], p<0.001, for mild, severe and critical state, respectively). Moreover, 27 subjects out of 170 (16%) showed high sensitivity troponin values higher than the 99 percentile upper reference limit stratified among previously defined severity classes as follows n=2 (2.4%), n=7 (15.9%) and n=18 (45.0%), respectively.

Conclusions:
The distribution of the troponin values greater than the cut-off in the SARS-CoV-2 population indicates a myocardial suffering independently related to COVID19 infection. This phenomenon may partially explain the high risk of adverse outcome in COVID-19 patients with underlying CVD. Therefore, it may be reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized and personalized treatment strategies.
Abstract 14697: Nt-probnp and Outcomes in Patients With and Without Heart Failure Hospitalized With Severe Covid-19 Pneumonia
Authors: Yoo Jeanwoo , Grewal Prabhjot , Papamanoli Aikaterini , Mojahedi Azad , Nakamura Jacquelyn , Fung Jenny , Abata Joshua , Dhaliwal Simrat , Jacob Robin , Hotelling Jessica , Karkala Nikitha , Tsui Stella T , Rawal Sahil , Coritsidis Alexandra , Marcos Luis , Bloom Michelle , Skopicki Hal , Kalogeropoulos Andreas P
Published: May 2021

Introduction:
The value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in hospitalized patients with severe coronavirus disease 2019 (COVID-19) is unclear.

Hypothesis:
Elevated NT-proBNP is associated with worse prognosis in hospitalized COVID-19 patients regardless of history of HF.

Methods:
We evaluated the in-hospital course of 469 adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (need for high-flow O
2
). We excluded patients who required mechanical ventilation (MV) or died within 24h of admission. We used Cox regression models to examine the association of admission NT-proBNP with mortality and the composite of death or MV.

Results:
Admission NT-proBNP was available in 399 patients (85.1%) of this cohort.
Table 1
summarizes the patient characteristics according to history of HF (41/399 [10.3%]). After a median of 13 days (8-22), 107 patients (26.8%) died and 86 additional patients (21.6%) required MV and survived. Both HF (HR 3.65; 95%CI 2.32-5.77; P<0.001) and admission NT-proBNP (HR per log-2 [doubling] 1.35; 95%CI 1.27-1.44; P<0.001) were strongly associated with mortality. In models adjusting for age, sex, race, body mass index, hypertension, diabetes, coronary artery disease, atrial fibrillation, chronic lung disease, chronic kidney disease, and baseline 0
2
saturation, every log-2 higher admission NT-proBNP was associated with 28% higher mortality in patients with HF (HR 1.28; 95%CI 1.02-1.61; P=0.037) and 26% higher mortality in patients without HF (HR 1.26; 95%CI 1.14-1.40; P<0.001), P for interaction 0.92. Admission NT-proBNP was also associated with the composite of death or MV in the entire cohort (adjusted HR per log-2 1.09; 95%CI 1.02-1.17; P=0.017).

Conclusions:
In these high-risk COVID-19 patients, admission NT-proBNP was strongly predictive of mortality regardless of HF. Elevated NT-proBNP may thus identify patients in need of cardioprotective measures.
Abstract 14698: Matrix Stiffening Induces a Pathogenic Qki-microrna-7-srsf1 Axis in Pulmonary Arterial Endothelial Cells
Authors: Woodcock Chen-shan J , Hafeez Neha , Handen Adam , Tang Ying , Estephan Leonard , Speyer Gil , Kim Seungchan , Bertero Thomas , Chan Stephen Y
Published: May 2021

Introduction:
Early increases in pulmonary artery stiffness drive pathogenic alterations of pulmonary arterial endothelial cells (PAECs), leading to vascular remodeling, a prominent feature of pulmonary hypertension (PH). However, the molecular mechanisms by which PAECs respond to altered extracellular matrix (ECM) mechanics remain unclear. Recent RNA sequencing study of PAECs exposed to stiff versus soft matrices has identified miRNA-7 (miR-7) as a mechanosensitive downregulated miRNA. The biogenesis of miR-7 is inhibited by the RNA binding protein quaking (QKI), which is shown to be correspondingly upregulated in ECM stiffness. Moreover, subsequent RNA sequencing and computational analyses have identified serine and arginine rich splicing factor 1 (SRSF1) as a miR-7 target in PAECs with ECM stiffening.

Hypothesis:
The QKI-miR-7-SRSF1 axis is a pivotal ECM stiffening-mediated pathogenic signal in PAECs.

Methods:
Human PAECs were cultured on soft (0.5 or 1 kPa) or stiff (50 kPa) matrices. Lungs from PH patients and rats (SU5416/Hypoxia- and MCT-exposed models) were used to evaluate genes and miRNA expression. Boyden chamber migration analysis examined PAEC mobility.

Results:
In human and rat PH lungs, miRNA-7 (miR-7) was down-regulated (
P
< 0.05). To validate RNA sequencing data by RT-qPCR, QKI level was increased (2.13 ± 0.19,
P
<0.0001) in PAECs cultured on stiff versus soft matrices and correspondingly miR-7 level was decreased (0.71 ± 0.17,
P
<0.0001). Furthermore, miR-7 targeted the 3’-untranslated region of SRSF1 mRNA as demonstrated by luciferase activity assay. In PAECs, forced miR-7 overexpression decreased SRSF1, and conversely miR-7 inhibition increased SRSF1. QKI overexpression increased SRSF1 by downregulating miR-7 level. Moreover, forced miR-7 overexpression significantly inhibited PAEC migration (
P
<0.0001), accompanied by downregulation of SRSF1 mRNA level (0.75 ± 0.07,
P
<0.0001).

Conclusions:
Our data demonstrate that mechanoactivation of a QKI-miR-7-SRSF1 signal axis promotes PAEC pathophenotypes driven by ECM stiffness. These insights broaden our understanding of RNA pathobiology in vascular stiffening and carry important therapeutic implications in PH.
Abstract 14709: Dual Pathology of Severe Aortic Stenosis and Cardiac Amyloidosis: Multi-center Study of Prevalence and Outcome
Authors: Nitsche Christian , Scully Paul , Patel Kush , Kammerlander Andreas , Wollenweber Tim , Thornton George , Pugliese Francesca , Kelion Andrew , Mullen Michael , Fontana Marianna , Hawkins Philip , Menezes Leon , Moon James C , Mascherbauer Julia , Treibel Thomas
Published: May 2021

Background:
Elderly patients with severe aortic stenosis (AS) are increasingly diagnosed with cardiac amyloidosis (CA). It is unclear whether dual AS-CA has worse outcomes or may even result in futility of transcatheter aortic valve replacement (TAVR).

Objective:
To identify diagnostic predictors and outcomes of AS-CA compared to lone AS.

Methods:
Severe AS TAVR referrals at three international sites underwent clinical and laboratory assessment, six-minute walk test, ECG, transthoracic echocardiography with strain analysis, and blinded research 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) prior to intervention. Transthyretin CA (ATTR) was diagnosed by bone scintigraphy, unremarkable serum/urine free light chain assessment; light-chain CA (AL) was diagnosis by endomyocardial biopsy. All-cause mortality was captured from national registries.

Results:
408 patients (age 83.4±6.5 years, 49.8% male) were recruited. DPD bone scintigraphy was positive in 11.6% (n=47, Grade-1 3.7%[15]) Grade-2/3 7.9%[32]). Positivity was associated with QRS duration (OR 2.5, 95%CI 1.1-5.5, p=0.02), voltage/mass-ratio (OR 0.4, 95%CI 0.2-0.9, p=0.02), history of carpal tunnel syndrome (OR 1.6, 95%CI 1.1-2.3, p=0.02). An additional two cases had biopsy proven AL-CA. Heart Team decision (blinded to bone scintigraphy) resulted in TAVR in 333 (81.6%), surgical aortic valve replacement in 10 (2.5%) and medical management in 65 (15.9%). After a median of 1.7 years, 22.9% of patients had died. AS-CA had a worse 1-year mortality than lone AS (24.5 vs 13.9%, p=0.045, Figure 1A), but there was no difference post valve intervention (p=0.7), which improved outcomes in both lone AS and AS-CA compared to medical management (Figure 1B+C).

Discussion:
Dual pathology of AS-CA is common in elderly AS patients. AS-CA is prognostically slightly worse than lone AS, but not if treated by valve intervention. Based on this data, TAVR should not be witheld in AS-CA.
Abstract 14723: Autoreactive T Lymphocytes Activate Cardiac Endothelium Independently of Tnf-α and Cause Endothelial Dysfunction Through Exosomes in Experimental Autoimmune Myocarditis
Authors: Rolski Filip , Czepiel Marcin , Weglarczyk Kazimierz , Siedlar Maciej , Kania Gabriela , Błyszczuk Przemysław
Published: May 2021

Background:
Inflammatory heart diseases represent an important clinical problem, nonetheless data regarding activation of cardiac microvascular endothelial cells (MVECs) are limited.

Aim:
To examine influence of TNF-α and exosomes produced by heart-reactive CD4+ T lymphocytes on activation of cardiac MVECs.

Methods:
Experimental autoimmune myocarditis (EAM) was induced in wild-type (WT) and TNF-α-deficient (TNF-KO) mice. CD4+ T lymphocytes were isolated from EAM mice at day 21 and activated in vitro to produce conditioned medium and exosomes. Activation of MVECs was assessed by specific assays and leukocyte-to-endothelial adhesion was analysed under shear flow condition using the BioFlux microfluidic system.

Results:
TNF-KO mice showed lower prevalence of myocarditis when compared to WT mice (50% vs. 90%). Stimulation of MVECs with secretome of antigen-activated autoreactive T cells resulted in upregulation of adhesion molecules (ICAM-1, VCAM-1 and P-selectin), increased ROS and decreased NO production. Addition of anti-TNF-α neutralizing antibodies effectively blocked adhesion of leukocytes to MVECs activated with the conditioned medium. Endothelial activation and dysfunction induced by the conditioned medium were independent of TNF-α produced by T cells. Stimulation of MVECs with T cell-derived exosomes increased ROS and decreased levels of NO and eNOS activation, but exosomes neither increased expression of adhesion molecules in MVECs nor induced their ability to bind leukocytes.

Conclusions:
TNF-α promotes MVEC activation and EAM development. In this model, autoreactive T cells activate MVECs, and TNF-a produced by MVECs rather than T cells is essential in this process. On the other hand, endothelial dysfunction caused by T cells seems to be mediated mainly by exosomes.
Abstract 14725: Image-based Virtual-heart Predictions Co-localize With ECG-based Automated Localization of Scar-related Ventricular Tachycardias
Authors: Zhou Shijie , Sung Eric , Prakosa Adityo , Chrispin Jonathan , AbdelWahab Amir , Aronis Konstantinos , Horacek Milan , Sapp John L , Trayanova Natalia
Published: May 2021

Introduction:
We previously developed an LGE-MRI-based virtual-heart arrhythmia ablation targeting (VAAT) methodology to non-invasively determine potential ablation targets for infarct-related VT. However, it is unknown whether VAAT’s predictions correspond with surface ECG predictions.

Hypothesis:
We hypothesized that the VAAT predicted VT circuits and potential ablation lesions would co-localize with ECG-based VT-exit predictions from a previously validated population-derived automated VT exit localization (PAVEL) system.

Methods:
We retrospectively enrolled 5 post-infarct patients who underwent LV endocardial VT ablation and had pre-procedural 2D LGE-MRIs. The PAVEL system based on a population-derived statistical method was used to localize VT-exit sites onto one of 238 triangles on the patient-specific virtual-heart LV endocardial surface using 8 independent ECG leads (I, II, V1-V6). The VAAT methodology incorporating patient-specific scar and infarct border zone distributions was used to identify potential VT circuits and find ablation lesions.

Results:
Eleven induced VTs were analyzed. Ten VT-exit sites were localized onto the patient-specific virtual-heart LV endocardial surface by the PAVEL system, and were used for the comparisons. One VT-exit site was too basal to be localized onto the virtual-heart geometry. The spatial resolution of the 10 predicted VT-exit sites was 13.8 ± 1.8 mm. VAAT-predicted VT circuits and ablation lesions correlated well with all 10 predicted VT-exit sites. Lastly, VAAT ablation lesions fell within the regions ablated clinically.

Conclusions:
The VAAT-predicted VT circuits and ablation lesions matched VT-exit sites predicted by the surface ECG-based PAVEL system. Combining these two complementary technologies may improve accuracy for non-invasively identifying optimal ablation targets to increase ablation efficacy.
Abstract 14742: Deep Learning of Intracardiac Electrograms in Atrial Arrhythmia
Authors: Rodrigo Miguel , Rogers Albert J , Ganesan Prasanth , Alhusseini Mahmood , Narayan Sanjiv M
Published: May 2021

Introduction:
Intracardiac devices detect atrial fibrillation (AF) by rate and regularity, but any inaccuracies may cause inappropriate use of anticoagulants or anti-arrhythmic medications.

Hypothesis:
Machine learning of raw intracardiac electrograms can identify AF from other atrial arrhythmias better than traditional measures of rate or regularity and without using specific electrophysiological analyses such as dominant frequency (DF).

Methods:
In 86 persistent AF patients (25 female, age 65±11) we recorded 64 unipolar intracardiac electrograms over 60 seconds prior to ablation (fig A). We trained deep learning models (comprising 2X1D-convolutional layers and 2 dense layers) on successive 4-sec segments labelled AF or Flutter/tachycardia (AFL), using 10-fold cross-validation with 80% of patients for training and an independent 20% for testing. We compared results to classical statistical and machine learning (ML) analyses of electrograms featurized by 30 metrics of cycle length (CL), DF and autocorrelation-based metrics (AC; fig B).

Results:
Identification of AF varied between methods, but was modest for features of CL (c-statistic 0.70), DF (0.67) and AC (0.75). ML that combined features improved results: linear combination (c-statistic 0.95 ± 0.04), Bagged trees (0.92 ± 0.06), k-nearest neighbors (0.92 ± 0.06) and support vector machines (0.95 ± 0.04). Deep learning using raw electrograms as input (no featurization) provided AUC of 0.95 ± 0.05 (fig C).

Conclusions:
Detailed machine learning of raw intracardiac electrograms identified AF more accurately than traditional indices of rate, regularity, and dominant frequency. This approach could reclassify AF detection from devices to improve management, and may reveal novel AF phenotypes with distinct clinical courses.
Abstract 14782: Sex Comparisons in Anticoagulation Treatment for Atrial Fibrillation in a Large Rural Healthcare System
Authors: Rudeck Macaela N , Benziger Catherine P
Published: May 2021

Introduction:
Atrial fibrillation (AF) and flutter lead to increased risk of thromboembolism (TE). The CHA
2
DS
2
-VASc score is used to determine the risk of TE.

Objective:
We aim to evaluate the anticoagulation use across CHA
2
DS
2
-VASc scores calculated using a validated automatic calculator.

Methods:
An AF registry was created for patients with AF or atrial flutter who had seen a primary care or cardiology provider within the past 2 years (5/28/2018-5/28/2020). An automatic CHA
2
DS
2
-VASc calculator was integrated into the electronic medical record system at Essentia Health on 10/1/2019. High-risk of TE was defined as a score of ≥3 for females and a score of ≥2 for males. AF registry included demographics, anticoagulation prescription, CHA
2
DS
2
-VASc and ATRIA bleed score, contraindications, and presence of left atrial appendage (LAA) occlusion device.

Results:
A total of 10992 patients with AF or atrial flutter were included in the registry (74.8 ±11.8 years, 41.7% female). A total of 6703 (61.0%) had a CHA
2
DS
2
-VASc score calculated (mean score 3.9 ± 1.5). Mean ATRIA bleed score was 3.0 ± 2.0. Within these patients, 90.7% of males and 93.0% of females were at high-risk of TE. Of these high-risk patients, anticoagulation use was 82.7% for females and 83.5% for males and increased with increasing score (p<0.01 for males, p<0.01 for females) (Figure 1). Overall, 36.9% were prescribed NOAC, 47.0% warfarin, and 0.8% heparin. There was no sex difference in the prescription of NOAC (37.7% male vs. 35.9% female, p=0.1). Fewer than 1% had WATCHMAN LAA device (0.3% male vs. 0.4% female, p=0.5).

Conclusion:
Four out of 5 patients at increased risk of TE are prescribed an anticoagulant. Interventions to improve anticoagulation use in high-risk patients are needed. Figure 1. Anticoagulation prescription use in atrial fibrillation patients by CHA
2
DS
2
-VASc score and sex between 5/28/2018-5/28/2020 at Essentia Health (N=6703).
Abstract 14783: Association of Daily Step Count and Resting Heart Rate With Right Ventricular Function in Pulmonary Arterial Hypertension
Authors: MacKinnon Grant E , Whitmore Carolyn , Oggs Rashundra , Huang Shi , MALLUGARI RAVINDER , Hemnes Anna R , Brittain Evan
Published: May 2021

Introduction:
Remote activity monitoring may provide new insight into behavioral choices and exercise capacity in pulmonary arterial hypertension (PAH). Here, we report baseline data from a randomized behavioral intervention (NCT03069716) to increase step counts in PAH.

Hypothesis:
Higher daily step count and lower resting heart rate (RHR) are associated with better right ventricular (RV) function.

Methods:
We recruited functional class I-III patients with idiopathic, heritable, or connective tissue disease-associated PAH on stable therapy. Participants were provided a Fitbit Charge 3 device and monitored for two weeks as a run-in period to the trial. The 6MWD test and echocardiogram were performed at baseline. RV function was assessed by tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC). We conducted linear regression to examine associations between daily step count and RHR with RV function, adjusted for age, sex, and BMI.

Results:
In total, 42 subjects completed the run-in period (48 ± 11 years, 86% female, 64% functional class II). PAH etiology was 76% idiopathic, 17% heritable, and 7% connective tissue disease. Average daily step count, RHR, and 6MWD were 4718 ± 3521 steps, 72 ± 10 beats per minute, and 424 ± 106 meters, respectively. Only 2.9% of days monitored had missing data. Daily step count (Beta 0.37mm per 1,000 steps; p = 0.039) and RHR (Beta -0.19mm per beat; p = 0.017) were associated with TAPSE (
Figure
), and daily step count was associated with FAC (Beta 1.1% per 1,000 steps; p = 0.01). The 6MWD was modestly associated with daily step count (r = 0.35; p = 0.028) but not associated with RV function (p > 0.05).

Conclusions:
Remote activity monitoring is feasible in PAH and may provide important clinical information as an adjunct to clinic-based assessments of exercise capacity. Lower daily step count and a higher RHR are associated with poorer RV function. Interventions to increase daily activity warrant further investigation in PAH.
Abstract 14786: Women Wait Longer Than Men for First EKG When Self-Presenting With Suspected Acute Coronary Syndrome, A Review of the Irish National ACS Registry
Authors: Laffan Jack , Gibson William , McInerney Angela E , Hussein Hafiz , Byrne Robert
Published: May 2021

Introduction:
Women suffer longer delay times until diagnosis and treatment when presenting with ACS, despite cardiovascular disease being the biggest cause of death amongst women. European guidelines recommend that women and men with suspected ACS are managed according to a common protocol. We aimed to investigate whether differential system delay existed for women versus men due to longer wait time for initial EKG testing in patients who self-presented to the emergency room with suspected ACS, bypassing the pre-hospital diagnosis and warning system

Methods:
We retrospectively reviewed the Irish national ACS registry and identified all cases of patients who self-presented to the emergency room between 2013-2018. Those patients for whom accurate time delays were not recorded were excluded. Baseline characteristics were compared for both groups. We determined the wait time from presentation to first EKG for both groups and performed a Mann-Whitney U test to test the difference between the groups.

Results:
Total number of self-presenters was 714 (women 154, men 560), representing 13.2% of all patients in the registry. We excluded 54 due to inaccurate time recordings; 14 were excluded due to first EKG performed by a family doctor in the community. Women were older than men (mean age 66.3 vs. 59.2yrs, P=0.0000012) and had similar rates of diabetes mellitus (10.4% vs. 11.9%, P=0.63). More women were current smokers (45.4% vs. 37.3%, P=0.11), more likely to be hypertensive (58.5% vs 44.5%, P=0.002) and have a diagnosis of hyperlipidaemia (56.7% vs. 46.8%, P=0.048). Median wait times were longer for women compared with men: 25.0 min (IQ 13-74) vs. 18.0 min (IQ 8-42)( P=0.002)(see Figure).

Conclusion:
Women self-referring with suspected ACS to the emergency room had longer wait times for their first EKG compared with men despite being more likely to have an elevated cardiovascular risk factor profile. Differential wait times for EKG is an important contributor to system delay.
Abstract 14800: Presenilin 1 and Presenilin 2 Contribute to Mitophagy Including Alternative Pathway
Authors: Saito Tsunenori , Gottlieb Roberta A
Published: May 2021

Introduction:
Presenilin 1 (PS1) and presenilin 2 (PS2) are proteins that compose γ-secretase, which is a protease present in late endosome lysosomes. Recently, amyloid beta accumulation was found in the cardiomyocytes of Alzheimer's disease patients and cause cardiac dysfunction. Mutations in
PSEN1
and
PSEN2
, the causative genes of familial Alzheimer's disease, are involved in the development of dilated cardiomyopathy (DCM); however, their roles in cardiomyocytes have not been elucidated thoroughly.

Hypothesis:
We hypothesized that PS1 and PS2 might be playing a role in mitochondria-selective autophagy (mitophagy) of cardiomyocytes.

Methods:
Whole-exome sequencing of 32 DCM patients was focused on 29 autophagy-related genes and 16 genes encoding autophagy-related proteins. Based on the results, the expression of autophagy and mitophagy markers was examined using cultured rat cardiomyocytes silenced for
PSEN1
or
PSEN2
and exposed to starvation, 100 μM bafilomycin A1, inhibiting fusion between autophagosomes and lysosomes, or 10 μM carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP), a mitochondrial uncoupler used to induce mitophagy.

Results:
A variant of
PSEN2
(c.1262C>T) may be the cause of DCM in a 50-year-old Japanese man. Electron microscopic observation of myocardium revealed a fibrillar substance in the expanded T-tube, suggesting failure to clear aggregates. FCCP treatment caused an increase in microtubule-associated protein 1 light chain 3 (LC3)-II and p62 which was further enhanced in cells with silenced PS1 or PS2. Rab9, which is associated with the alternative pathway of mitophagy, was also increased in cells silenced for PS1 or PS2. Parkin was decreased with FCCP treatment, suggesting its clearance via mitophagy, and this was further enhanced when PS1 was silenced. Voltage-dependent anion channel (VDAC) levels, a reflection of mitochondrial content, were slightly increased when PS1 and PS2 were silenced. LC3-II increased with starvation and further increased with bafilomycin A1 treatment: however, silencing PS2 did not result in further increase, suggesting that flux was impaired.

Conclusions:
PS2 and probably PS1 are required to support autophagic flux necessary for cardiomyocyte homeostasis.
Abstract 14806: Circumstances Surrounding End of Life in Pediatric Heart Transplant: A Report From the Pediatric Heart Transplant Society
Authors: Cousino Melissa K , Yu Sunkyung , Blume Elizabeth , Henderson Heather T , Hollander Seth , Khan Sairah , Parent John J , Schumacher Kurt
Published: May 2021

Introduction:
The Institute of Medicine called for scientific investigation and the development of guidelines to improve end of life care for pediatric patients with serious illnesses. Despite high morbidity and mortality in pediatric heart transplantation (HTx), research on the end of life care needs of this population is extremely limited.
Aims:
This study aimed to describe the circumstances surrounding death of pediatric HTx patients and examine associations between location of death and technological interventions at end-of-life with demographic, disease, and HTx-related factors.

Methods:
This retrospective analysis of the Pediatric Heart Transplant Society registry utilized descriptive statistics and standard univariate analysis to examine associations between location of death and patient factors.

Results:
Of 9,217 registry entries, 2,804 (30%) deaths occurred; 1,310 while awaiting HTx; 1,494 post-HTx. Location of death was only recorded for 1,113 patients which included 804 waitlist deaths; 89% occurred in the hospital, primarily in ICU settings (74%) with most requiring mechanical ventilation (77%). A subset (39%) were supported by ECMO/VAD at time of death with 69% receiving inotrope support. Location of death was captured for 309 post-HTx patients with only 22% occurring in hospital; primarily in the ICU (74%) with half receiving mechanical ventilation (52%) and a smaller proportion supported by ECMO/VAD (18%) or inotropes (21%) at time of death. Overall, location of death was not associated with patient sex, race, ethnicity, insurance type, or primary etiology. Out of hospital death was associated with older patient age (p<0.01). Family decision to withdraw life-sustaining interventions was included as a contributing cause of death in 5.4% of waitlist cases and 3.5% of post-HTx cases.

Conclusions:
Death occurred in ~1/3 of patients captured in this pediatric HTx registry. ICU deaths with high use of technological interventions were common, particularly in waitlisted patients, but family decision to discontinue interventions was infrequently cited. Findings underscore the need for palliative care interventions and improved research strategies to better understand end of life in pre- and post-HTx pediatric populations.
Abstract 14817: Assessing the Burden of Cardiovascular Risk Factors and Disease Across PVDOMICS Cohorts
Authors: Leopold Jane A , Larive Brett , Rosenzweig Erika , Frantz Robert , Hassoun Paul , Hemnes Anna R , Rischard Franz , Jacob Miriam , Horn Evelyn M ,   PVDOMICS Study Group
Published: May 2021

Longitudinal trends demonstrate an increase in the prevalence of cardiovascular (CV) risk factors in the general population; however, the burden of CV risk factors or established disease in patients across WSPH groups remains unknown. Accordingly, we examined the prevalence of CV risk factors and established disease in the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) cohort. PVDOMICS enrolled 1,097 subjects with pulmonary hypertension (PH) (mPA ≥ 25 mmHg) and at-risk disease comparators (mPa < 25 mmHg) from six US centers. Compared to participants with PH attributable to left heart disease (LHD-PH; WSPH Group 2, n=145) who are expected to have a high burden of CV risk factors and disease, patients with WSPH Groups 1,3,4,and 5 (non-LHD-PH)(n=618) were younger (56.2 ± 14.5 vs 67.7 ± 11.7 yrs, p<0.02) with no difference in %female or race. Non-LHD-PH had a lower prevalence of the CV disease risk factors hypertension (38.6% vs. 66.7%, p<0.02), diabetes mellitus (21.4 vs. 41.0%, p<0.02), and metabolic syndrome (30.8 vs. 48.4%, p<0.02) compared to LHD-PH, while smoking, hypercholesterolemia, and family history of CV disease were similar between groups. The prevalence of established CV disease, including myocardial infarction, CABG or stent, stroke, arrhythmia, or peripheral arterial disease was significantly lower in non-LHD-PH than in LHD-PH. At right heart catheterization, although mPA pressures were similar between the groups, PVR (5.5[3.3, 8.7] vs. 3.7[7.2, 5.7] WU, p<0.02), and cardiac output were higher (5.4 ± 1.9 vs. 4.9 ± 1.6 L/min, p<0.02) in non-LHD-PH compared to LHD-PH. This corresponded to a higher left ventricular ejection fraction by echo (62.2 ± 8.2 vs. 54.0 ± 14.0 %, p<0.02) and greater 6-minute walk distance (361.8 ± 134.7 vs. 294.7 ± 118.7 m, p<0.02). Non-LHD-PH also had better cardiovascular health compared to LHD-PH with higher modified American Heart Association Life’s Simple 7 scores (6.7 ± 1.6 vs. 5.8 ± 1.5, P<0.02). Taken together, these data demonstrate that CV disease risk factors and CV disease are frequent comorbidities that occur in patients with non-LHD-PH, although CV health is not as impaired as in patients with LHD-PH. How this affects PH-related outcomes remains to be determined.
Abstract 14836: Dual Dysfunction of Kir2.1 at the Sarcolemma and the Sarcoplasmic Reticulum Underlies Arrhythmogenesis in a Mouse Model of the Andersen-Tawil Syndrome Type 1
Authors: Macias Alvaro , González-Guerra Andrés , Moreno Manuel Ana Isabel , Cruz Uréndez Francisco Miguel , Nieves García , Gutierrez-Espinosa de los Monteros Lilian Karina , Roche Marta , Bermúdez Jimenez Francisco José , Vera-Pedrosa María Linarejos , Bernal Juan A. , Jalife Jose
Published: May 2021

Introduction:
Andersen-Tawil syndrome type 1 (ATS1) is associated with fatal cardiac arrhythmias. However, the underlying mechanisms are poorly understood.

Hypothesis:
Cardiac-specific expression of trafficking deficient Kir2.1 channels in mice
in-vivo
recapitulates the cardiac electrical phenotype of ATS1 and investigate the underlying mechanisms.

Methods:
We generated a new mouse model of ATS1 by a single i.v. injection of cardiac specific adeno-associated viral (AAV) transduction with Kir2.1
Δ314-315
, which recapitulated the ATS1 ECG phenotype without modifying ventricular function. The animal and cellular, structural and functional analyses were carried out by ECG, intracardiac stimulation, patch-clamping, membrane fractionation, western blot, immunolocalization and live calcium imaging.

Results:
AAV-Kir2.1
Δ314-315
mice were significantly more sensitive to flecainide than control, increasing the PR and QRS intervals over time. Kir2.1
Δ314-315
mice had increased vulnerability to cardiac fibrillation. Patch-clamping in ventricular cardiomyocytes from Kir2.1
Δ314-315
mice demonstrated significantly reduced

I
K1

and

I
Na

, depolarized resting membrane potential and prolonged action potential. Immunolocalization in control mice revealed two bands of Kir2.1 staining, one colocalizing with Na
V
1.5 and AP1 near the Z disk, the other near the H zone. Membrane fractionation and western blot experiments demonstrated two distinct levels of Kir2.1 protein expression, one at the sarcolemmal fraction together with Na
V
1.5 and the other at the sarcoplasmi creticulum (SR). Kir2.1
Δ314-315
cardiomyocytes showed disruption of the Kir2.1-Nav1.5 channelosome at the sarcolemma, indicating dysfunctional trafficking o fboth channels. In addition, the SR Kir2.1 was disrupted and calcium transient dynamics were altered, resulting in frequent abnormal spontaneous calcium release events, and revealing an excitation-contraction coupling defect.

Conclusions:
Cardiac-specific AAV transduction with Kir2.1
Δ314-315
in mice recapitulates the ATS1 phenotype by disrupting localization and function of Kir2.1at the SR, and the Kir2.1-Na
V
1.5 channelosome at the sarcolemma, revealing anovel dual mechanism of arrhythmogenesis.
Abstract 14840: Ability of Coronary Calcium Absence to Predict Negative Stress Test Results in Patients Considered for Flecainide Therapy
Authors: Anderson Jeffrey L , Knight Stacey , McCubrey Raymond , May Heidi T , Min David B , Cutler Michael J , Bunch T Jared J , Muhlestein Joseph B , Knowlton Kirk U
Published: May 2021

Background:
Flecainide is a useful antiarrhythmic for atrial fibrillation (AF). However, the Cardiac Arrhythmia Suppression Trial (CAST) showed an increased risk of fatal ventricular arrhythmia with flecainide use after myocardial infarction (MI). Thus, a history of MI or coronary artery disease (CAD) is a flecainide exclusion, and stress testing is used to exclude ischemia. We assessed whether absence of coronary artery calcium (CAC) can obviate the need for stress testing.

Methods:
We assessed ischemic burden using regadenoson Rb-82 PET/CT in 1375 AF patients (pts) ≥50 y old without clinical CAD. CAC was determined qualitatively in these pts by low dose attenuation CT (n=816) or by quantitative CT (n=559). The primary comparison was percentage of pts with ischemic burden ≥5% by CAC presence or absence.

Results:
Pts with CAC absent (n=433, 31.5%) were younger, heavier, with lower rates of diabetes, hypertension, and dyslipidemia. Average ischemic burden was lower in CAC-absent pts (0.8 ± 3.1 v 1.3 ± 3.7, p=0.04), and a favorable difference trend in ischemic burden ≥5% was noted that did not reach significance (7.2% v 9.7% p=0.15). CAC-absent pts showed greater coronary flow reserve (2.4 v 2.3, p=0.002) and trended to have fewer referrals for coronary angiography (1.6% v 4.0% adjusted[adj]*-p=0.10), fewer findings of obstructive CAD (1.4% v 3.5% adj-p=0.12), and lower rates of 90-day MACE (1.6% v 3.5%, adj-p=0.12); long-term MACE were fewer (5.3% v 7.0% adj-p=0.04).

Conclusions:
Our results support the hypothesis that an easily administered, inexpensive, low radiation CAC scan may identify a subset of flecainide candidates with a low ischemic burden on PET stress testing and that rarely need coronary angiography/intervention. CAC-absence combined with other clinical information may obviate the need for routine stress testing in selected flecainide candidates. Larger and randomized trials are indicated to confirm these findings and apply CAC use in clinical practice.