bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15414: Cardiac Dyssynchrony and Strain Do Not Predict Deterioration of Ventricular Function in Patients With Repaired Tetralogy of Fallot
Authors: Jing Linyuan , Suever Jonathan D , Charnigo Richard J , Alhadad Sudad , Stearns Evan , Mojsejenko Dimitri , Haggerty Christopher M , Hickey Kelsey , Valente Anne M , Geva Tal , Powell Andrew J , Fornwalt Brandon K
Published: July 2021

Objectives:
Patients with repaired tetralogy of Fallot (rTOF) suffer from progressive ventricular dysfunction decades after their initial surgical repair. This study sought to determine whether measures of ventricular strain and dyssynchrony could predict deterioration of ventricular function in patients with rTOF.

Methods:
A database search identified all patients at a single institution with rTOF who underwent cardiac magnetic resonance (CMR) at least twice, greater than 6 months apart, without intervening surgical or catheter procedures. Five primary potential predictors were derived from the first CMR using a custom feature tracking algorithm: left (LV), right (RV) and inter-ventricular dyssynchrony, and LV and RV peak circumferential strains. Three outcomes were defined as measures of progression over time: RV end-diastolic volume, RV ejection fraction (EF), and LV EF. A multivariate linear mixed model, subject to backward elimination of extraneous terms, was fit to investigate relationships between predictors and outcomes. Ten potential confounders (see table footnote) measured at baseline were also included in the model.

Results:
A cohort of 153 patients with rTOF (23±14 years, 50% male) were included. The mean time between the first and last CMR was 2.9±1.3 years. None of the 5 primary predictors were significantly associated with change over time in the 3 outcomes in the multivariate model, though RV circumferential strain was associated with RV EF at baseline (table). Only 1-16% of the variability in the change over time in the 3 outcomes could be explained by the predictors in the multivariate model.

Conclusions:
In patients with rTOF, measures of ventricular dyssynchrony and strain were not significantly related to changes in ventricular size and function over time in a multivariate analysis. The ability to predict deterioration in ventricular function using all potential predictors is limited.
Abstract 15481: LV Systolic Dysfunction is Improved by TAVR: Insights From the French-American Registry
Authors: Damluji Abdulla , Alansari Yahya E , Dyal Michael , Murman Magdalena , Kabach Mohamad , Novoa Italo , Simek Shawn C , Simek Shawn C , Carrillo Rogerio , Williams Donald , De Marchena Eduardo J , Martinez Claudia A , Alfonso Carlos E , Moscucci Mauro , Cohen Mauricio G , Leroux Lionel , Heldman Alan W
Published: July 2021

Introduction:
We sought to describe changes in left ventricular ejection fraction (LVEF) after TAVR procedures.

Methods:
This is an observational study from 04/2008 to 06/2015 of all consecutive adults who received TAVR for severe symptomatic AS with Edwards Sapien or Medtronic CoreValve at two tertiary academic centers in USA and France.

Results:
Of 765 patients who received TAVR, 716 (94%) had follow-up echocardiography. Of those, 513 (72%), 143 (20%), 60 (8%) had a baseline EF>50%, EF 30-49%, and EF<30, respectively. Patients with EF < 30% were more likely to be Hispanic males. There were no differences in age, CVD risk factors, or history of multivessel coronary disease among groups. Patients with EF<30% were more likely to have AICD implantation and paced rhythm. All groups had similar rates of IABP insertion for hemodynamic support (EF≥50%: 6%, EF<30-49%: 9%, EF<30: 5%, p=0.544), procedural success (EF≥50%: 94%, EF<30-49%: 97%, EF<30: 98%, p=0.180), in-hospital mortality, procedural complications, and complete heart block. However, one-year all-cause-mortality was higher if baseline LV systolic function was abnormal (EF≥50%: 6%, EF<30-49%: 14%, EF<30: 9%, p=0.036). On 30-day follow-up echocardiography, absolute improvement in LVEF was highest among patients with EF<30% (Figure 1). If baseline LVEF was reduced, unchanged or improved mitral regurgitation were associated with improved LV function on follow-up (Figure 2).

Conclusion:
Transcatheter treatment of severe symptomatic AS is safe and feasible, even in patients with LVEF<30%. Most patients with LVEF<50% had increased EF after TAVR procedures.
Abstract 15493: Renal Sympathetic Denervation Reduces Ventricular Arrhythmias Inducibility in Dogs With Healed Myocardial Infarction
Authors: Huang Bing , Yu Lilei , Lu Zhibing , He Bo , Wang Zhuo , Zhou Liping , Jiang Hong
Published: July 2021

Introduction:
Previous studies have suggested that renal sympathetic denervation (RSD) could suppress acute myocardial ischemia-induced ventricular arrhythmias (VAs), but the long-term effects of RSD in a post-infarction canine model is not fully established.

Methods:
Thirty dogs underwent embolization of the left anterior descending artery. After a 14-days of recovery period, all the dogs were equally randomized to the RSD, medicine (MED; carvedilol 12.5mg PO BID), or control (CTRL; no therapy) group. Animals were monitored for 3 months after interventions. The serum norepinephrine (NE), echocardiographic indices, heart rate variability (HRV), and VAs inducibility were measured at the end of 90-day follow-up. Tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43) expressions in the peri-infarcted zone were also determined immunohistochemically. The protein levels of metrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitor of matalloproteinases (TIMP-1) were also determined.

Results:
When compared with CTRL group, RSD significantly (1) decreased heart rate, serum NE, sympathetic nerve indices of HRV, and the density of both TH- and GAP43-positive nerves in the peri-infarcted zone; (2) increased left ventricular ejection fraction and reduced left ventricular dilatation; (3) decreased the protein levels of MMP-2, MMP-9 and TIMP-1 in left ventricular tissues; (4) decreased the inducibility of ventricular tachyarrhythmias. Beta-receptor blockade by carvedilol showed comparable effects.

Conclusions:
RSD could reduce VAs inducibility in a canine model of healed myocardial infarction. Inhibition of autonomic and structural remodeling by RSD may be responsible for this salutary result.
Abstract 15507: CPR Education in Middle School Students During Physical Education Class
Authors: Watanabe Kae , Lopez-Colon Dalia , Shuster Jonathan J , Philip Joseph
Published: July 2021

Introduction:
AHA advocates for CPR education as a required element of the secondary school curriculum. Unfortunately, many states have not adopted CPR education as part of their standard curriculum. Our aim was to investigate a low-cost, and time effective method to educate students on Basic life Support (BLS) during a physical education (PE) class, including evaluation of the use of re-education.

Hypothesis:
We hypothesize that a 45 minute BLS class during PE class is sufficient to provide with CPR and AED knowledge and skills.

Methods:
This is a prospective, randomized study. The study included forty one 8
th
grade students in an Alachua County Middle School in Gainesville, Florida. Education was performed by an AHA-certified provider during a 45 minute PE class. Education was limited to chest compressions and the usage of an Automatic External Defibrillator (AED). Students were randomized into two groups; one group received repeat education at two months post-initial education, while the second group did not. Students had a skills and knowledge test administered pre- and post-education, given after initial education and repeated two and four months later to assess retention. Total scores were compared between pre- and post- education, as well as between groups.

Results:
There was a significant difference in CPR skills and knowledge when comparing pre- and post-education results for all time-points (p<0.001). When assessing retention, no significant difference in mean total scores was observed between the initial post-education as compared to two and four months (p>0.1). Mean total scores compared between groups showed no statistical significance of re-education. However, a statistical significance was noted for AED usage in the repeat education group.

Conclusions:
Our study indicates significant increase in CPR knowledge and skills following a one-time 45 minute session. Repeat education may be useful as a yearly event, but would need further investigation. If schools across the United States invested one 45-60 minute period a year for each school year, this would ensure widespread CPR knowledge with minimal cost and loss of school time.
Abstract 15618: Anatomy Does Matter: The Relationship Between Catheter-Tissue Contact Force and Anatomical Variations of Left Atrium
Authors: Sairaku Akinori , Nakano Yukiko , Suenari Kazuyoshi , Kihara Yasuki
Published: July 2021

Background:
Adequate catheter-to-myocardial contact force (CF) and catheter stability are important to create transmural lesions during catheter ablation of atrial fibrillation (AF). It is known that there are anatomical variations in left atrium (LA) and it is related to the outcome after the ablation. We tested any relationship between the CF and LA anatomical variations.

Methods:
Consecutive patients undergoing radiofrequency-based extensive encircling pulmonary vein (PV) isolation for the treatment of paroxysmal AF were dichotomized according to the LA anatomical variations; patients who had a PV-bifurcation region of LA ridge that was steep enough to enable a stable catheter-tip contact or a left common PV (group 1, the red arrows in Figure 1), or those who had neither (group 2, the blue arrows in Figure 1). The blinded operators carried out the procedure with the use of CARTO system, and the following VisiTag™ module setting was applied; a minimum time spent in an area of 5 seconds, a maximum distance the catheter has moved of 4mm, a force over time of 25%, and a minimum force of 10g. Low-CF tags was defined as ablation tags on CARTO map located at anterior aspect of left PVs that did not fulfill the pre-determined VisiTag™ criteria. The endpoints were the number of low-CF tags and freedom from AF 1 year after the ablation.

Results:
Patients in group 1 (n=31) had a smaller number of low-CF tags than those in group 2 (n=55, 2.8±2.1 vs. 5.9±3.8; p=0.013). Freedom from AF was more common in group 1 compared to group 2 (80.6% vs. 60%; p=0.04), and was independently associated with the number of low-CF of <3 (hazard ratio 2.4, confidence interval 1.12-6.87; p=0.026).

Conclusions:
Contact of the catheter-tip with the tissue may predict outcome after AF ablation, and it may depend on LA anatomical variations.
Abstract 15631: The Hemodynamic Determinants and Physiologic Correlates of QTc Interval Using Impedance Cardiography in Heart Failure
Authors: Khraim Fadi , Pike Rodolfo , Williams Jennifer , Al-Zaiti Salah S
Published: July 2021

Background:
Prolonged QTc interval is a known risk factor for adverse cardiac events, including sudden and non-sudden cardiac death. Understanding the determinants and physiologic correlates of QTc can guide the proper strategy for the primary prevention of sudden death in high risk patients.

Methods & Results:
This was an observational study that recruited ambulatory heart failure patients (NYHA I-III) from an outpatient clinic in NL, Canada. In supine resting position, consented participants underwent non-invasive 12-lead ECG and hemodynamic monitoring using BioZ Dx Impedance Cardiography (Sonosite Inc., WA, USA). ECGs were evaluated by a reviewer blinded to clinical data. Participants with pacing (n=12) or left bundle branch block (n=9) were excluded. Three measures of interest were automatically computed: (1) QTc interval (i.e., from QRS onset to T offset), (2) QRS duration (i.e., from QRS onset to QRS offset), and (3) JTc (i.e., QTc interval minus QRS duration). Effect sizes were computed using Pearson’s r coefficients. The final sample (n=23) was 62±13 years of age and 70% male with LVEF of 34±10%. The mean QTc was 441±39 milliseconds, and 10 patients (43%) had prolonged QTc (≥450 milliseconds). QTc interval negatively correlated with cardiac output (r= -0.57), and positively correlated with systemic vascular resistance (r= +0.57), as well as thoracic fluid content (r= +0.43). QRS duration alone was not specifically associated with any hemodynamic parameter, but JTc interval positively correlated with total arterial compliance (r=+0.42).

Conclusions:
In heart failure patients, we interestingly found that increased systemic vascular resistance results in QTc interval prolongation, where repolarization time is specifically influenced by arterial compliance. This suggests potential benefit from antihypertensive therapy targeted at lowering systemic vascular resistance in those with prolonged QTc/JTc. Nevertheless, these intervals need to be interpreted with caution in patients with thoracic fluid overload (e.g., pulmonary edema).
Abstract 15636: Percutaneous Intervention (PCI) Improves Outcomes in Out of Hospital Cardiac Arrest (OHCA) Patients Receiving Coronary Angiography
Authors: Scutella Michael G , Pike Francis , Fitzgibbon James , Kowalski Lindsey , Callaway Clifton , Rittenberger Jon , Reynolds Josh , Dezfulian Cameron
Published: July 2021

Introduction:
Acute coronary occlusion is common after OHCA. PCI may reduce subsequent cardiac death and improve cerebral perfusion thus improving outcomes. Recent studies suggest these benefits may be attenuated in patients with more severe brain injury.

Hypothesis:
PCI will more strongly associate with improved outcome than just coronary angiography (CA) after OHCA with loss of association in those with greatest brain injury.

Methods:
In subjects with OHCA with unclear arrest etiology, we examined the association between CA (with or without PCI) and PCI with 1) hospital survival; 2) discharge cerebral performance category (CPC); 3) discharge modified Rankin scale (mRS); 4) discharge destination. All outcomes were dichotomized and associations adjusted for propensity to perform 1) CA and 2) PCI based on associated pre-CA factors. This analysis was repeated after stratifying the cohort based on early brain injury as measured by Pittsburgh Cardiac Arrest Category (PCAC) dichotomized as PCAC 4 (severe injury) and PCAC 1-3 (mild to moderate).

Results:
Early (<24 h) CA was performed in 284/600 (47%) OHCA and PCI in 151/284 CA (53%). In unadjusted analysis, performance of both CA and PCI was strongly associated with improved outcomes (all p < 0.0001). Adjustment based on propensity to perform CA reduced the average treatment effect (ATE) to a non-significant 7-8% trend whereas adjustment based on propensity to perform PCI demonstrated a highly significant ATE of ~14-15% (p < 0.01) whereas those with less severe brain injury had trends to benefit with CA, which became significant (most p<0.01) with PCI.

Conclusion:
Early selection for CA of OHCA survivors likely to require PCI without severe brain injury is associated with substantial outcome benefits. The observed treatment effect is significantly reduced in patients with early signs of significant brain injury.
Abstract 15641: Quantification of Left Ventricular Shape Differentiates Pediatric Pulmonary Hypertension Patients From Matched Controls
Authors: Wagner Jennifer L , Landeck Bruce F , Hunter Kendall
Published: July 2021

Background:
Changes in left ventricular (LV) shape are observed in patients with pulmonary hypertension (PH). Quantification of shape changes could serve as an additional tool to non-invasively monitor pediatric patients with PH. Decomposing the shape of a ventricle into a series of components and magnitudes will facilitate differentiation of healthy and PH subjects.

Methods:
Parasternal short axis echo images acquired from 42 pediatric subjects with PH as well as 42 age and sex matched normal control subjects underwent speckle tracking using Velocity Vector Imaging (Siemens) to produce series of x,y coordinates tracing the LV endocardium in each frame. A Fourier transform was then used to derive shape components and magnitudes from LV shape in each frame. Magnitudes from the first 11 components were normalized to heart size (magnitude/LV length as measured on apical view) and analyzed across a single cardiac cycle.

Results:
Fourier decomposition produced a series of shape components from short axis echo views of the LV (Figure 1). All 11 components analyzed were significantly different between groups (Figure 2).

Conclusion:
Quantification of LV shape can differentiate normal pediatric subjects from those with PH. Shape analysis is a promising new method to precisely describe shape changes observed in PH. Differences between groups speak to intra ventricular coupling that occurs in right ventricular overload and may describe phenomena such as mechanical hinge points at the septal-wall interface, myocardial discontinuities or deformations from reflected pressure waves. Further analysis surrounding timing and correlation to clinical parameters is underway.
Abstract 15694: Roles of Nitrite and Metformin in Severe Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction (PH-HFpEF)
Authors: Lai Yen-Chun , Tabima Diana , Vanderpool Rebecca , Hu Jian , Goncharov Dmitry , Goncharova Elena , Tofovic Stevan , Mora Ana , Gladwin Mark
Published: July 2021

Background:
PAH (Group I) is a disease of the small pulmonary arteries, characterized by vasoconstriction, vascular proliferation and remodeling. PH-HFpEF (Group II) is known to occur secondary to the LV diastolic dysfunction and is recognized as a clinical complication of metabolic syndrome, with no currently approved therapies. Since the use of conventional therapies for PAH in PH-HFpEF patients is often ineffective, targeting both pulmonary vascular disease and metabolic disorders appears to be a key strategy for the treatment of PH-HFpEF. We, as well as others, have reported that nitrite exhibits therapeutic efficacy in moderate PAH models and improves glucose metabolism. In addition, metformin, the canonical AMPK activator and the first-line anti-diabetic drug, has been found to prevent the development of moderate PAH. In this work, we examined the effects of nitrite and metformin in PH-HFpEF, and compared their effects in severe PAH.

Methods and Results:
Nitrite (100mg/L) and metformin (300mg/kg) were given in drinking water to rats with Su5416/hypoxia-induced severe PAH or to rats with Su5416/metabolic syndrome-induced PH-HFpEF for 6 and 14 weeks, respectively. In the PH-HFpEF rats, our data showed that both nitrite and metformin treatments reduced pulmonary pressures and pathological vascular remodeling and limited hyperglycemia, which correlated with increased SIRT3-AMPK activation in skeletal muscles and AMPK activation in pulmonary vessels. Similar protective effect of nitrite was also observed in Su5416/hypoxia rats, together with increased activation of SIRT3 and AMPK in skeletal muscles. However, metformin failed to reduce pulmonary pressures and vascular remodeling in Su5416/hypoxia rats, with unchanged activation levels of SIRT3 and AMPK, suggesting metformin may favorably affect PH only in the presence of metabolic disorders. In addition, the AMPK agonist AICAR was found incapable of limiting PAH in Su5416/hypoxia rats.

Conclusions:
Our findings indicate that oral nitrite treatment limits PH-HFpEF, as well as PAH, while metformin treatment more preferentially improves PH-HFpEF. Our findings also indicate that activation of SIRT3-AMPK may represent a potential therapeutic route in the treatment of both PAH and PH-HFpEF.
Abstract 15705: Chronic Inhaled Acrolein Depresses Circulating Endothelial Progenitor Cells and Promotes Atherosclerosis
Authors: Conklin Daniel J , Agarwal Abhinav , Sithu Srinivas , Zeller Iris , Haberzettl Petra , O'Toole Timothy E , Bhatnagar Aruni , Srivastava Sanjay
Published: July 2021

We have previously shown that acute exposure to air pollutants including particulate matter or the volatile acrolein leads to reversible suppression of circulating angiogenic cells in humans and mice. Exposure to tobacco smoke, which contains both particles and aldehydes such as acrolein, also suppresses EPC number and function in association with an increase in cardiovascular disease risk. To assess whether acrolein alone worsened vascular pathogenesis, we exposed mice to acrolein (1 ppm * 6h/day) in a murine model of hind limb ischemia. Mice were exposed to acrolein for 4 days prior to permanent right femoral artery and vein ligation and bisection (distal to inguinal ligament) with continued exposure to filtered air (control) or acrolein for another 2 weeks. Blood flow recovery in the ischemic hind limb was measured via Laser Doppler Perfusion Imaging (LDPI) and normalized as a percentage of flow in the non-ischemic limb. Although acute exposure to acrolein reduced the number of circulating angiogenic cells it had only a modest effect blood flow recovery after 7 days (% Recovery: air, 86.2±21.4; acrolein, 68.3±21.6, n=8,8, p=0.12). Hence to determine whether chronic acrolein exposure worsened chronic vascular injury, we exposed C57BL/6J mice to 1 ppm acrolein for 12 weeks. This long-term exposure significantly depressed (by 51%) circulating levels of Flk-1+/Sca-1+ cells (as % of lymphocytic counts: air 0.15±0.09; acrolein 0.07±0.05; p<0.02). To tested if cell changes were associated with changes in atherogenesis, apoE-null mice on normal chow or high-fat diet were exposed to chronic acrolein (1 ppm; 12 week). Acrolein accelerated aortic atherosclerosis by 1.6-fold (p<0.001) but it did not affect coincident dyslipidemia (total cholesterol: air, 1224±189; acrolein, 1076±195 mg/dL) compared with air-exposed, HFD-fed mice. These results suggest that that chronic low level acrolein exposure suppresses circulating angiogenic cells and accelerates atherogenesis; hence the atherogenic effect of exposure to traffic pollutants, indoor smoke or cigarette smoke may be in part attributable to acrolein. These findings could inform exposure risk assessments and the development of new policies for regulating pollutant exposure and tobacco product use.
Abstract 15727: Platelet Inhibition With Ticagrelor and Clopidogrel in Comatose Survivors of Out-of-Hospital Cardiac Arrest
Authors: Steblovnik Klemen , Blinc Ales , Mijovski Mojca B , Fister Misa , Mikuz Ursa , Noc Marko
Published: July 2021

Comatose survivors of out-of-hospital cardiac arrest (OHCA) nowadays frequently undergo immediate percutaneous coronary intervention (PCI) which is associated with the need for antiplatelet therapy with P2Y12 inhibitors. In the present study we investigated platelet inhibition in 19 comatose survivors of OHCA undergoing PCI and hypothermia (32-34
o
C) who were randomized to clopidogrel 600 mg loading followed by 75 mg/day (n=6) or ticagrelor 180 mg loading followed by 90mg bid (n=13) administered as crushed and dissolved tablets via nasogastric tube. Platelet inhibition was measured by VerifyNow® and Multiplate® aggregometry at baseline, and 2, 4, 12, 22 and 48 hours after loading dose. VerifyNow® revealed greater platelet inhibition with ticagrelor becoming statistically significant 12 hours after the loading (Figure). Also Multiplate ADPtest revealed greater platelet inhibition after ticagrelor at 4 hours (21.5±13.9 vs. 38.7±16.8, p=0.03), 12 hours (15.4±12.0 vs. 36.3±8.7, p<0.01) and 22 hours (14.3±6.1 vs. 26.3±4.3, p<0.01). Accordingly, our preliminary results indicate that ticagrelor has faster and stronger antiplatelet effect than clopidogrel during the initial 48 hours of postresuscitation phase and maybe a P2Y12 of choice in comatose survivors of OHCA undergoing PCI.
Abstract 15733: Long-Term Follow-Up of Patients With Paroxysmal Atrial Fibrillation and Severe Left Atrial Scarring: Comparison Between Pulmonary Vein Antrum Isolation Only or PVAI Combined With Either Scar Homogenization or Trigger Ablation
Authors: Mohanty Sanghamitra , Mohanty Prasant , Di Biase Luigi , Trivedi Chintan , Bai Rong , Santangeli Pasquale , Sanchez Javier , Hranitzky Patrick , Gallinghouse G. J , Al-Ahmad Amin , Horton Rodney , Hongo Richard , Hao Steven , Beheiry Salwa , Elayi Claude S , Lakkireddy Dhanunjay , Reddy Y. Madhu , Viles Gonzales Juan F , Burkhardt John David , Natale Andrea
Published: July 2021

Background:
Left atrial (LA) scarring, a consequence of cardiac fibrosis is a powerful predictor of procedure-outcome in atrial fibrillation (AF) patients undergoing catheter ablation. We sought to compare the long-term outcome in patients with paroxysmal AF and severe LA scarring/fibrosis identified by 3D mapping undergoing ablation of the pulmonary veins (PVAI) only or PVAI and the entire scar areas (scar homogenization) or PVAI plus ablation of the non-PV triggers.

Methods:
One-hundred seventy seven consecutive patients with paroxysmal atrial fibrillation and severe left atrial scarring were included in this study. LA scarring was diagnosed by 3D voltage mapping. The degree of scar was described as severe when >60% of the LA area was involved. Non-PV triggers were defined as ectopic triggers originating from sites other than pulmonary veins such as interatrial septum, superior vena cava, left atrial appendage, ligament of Marshall, crista terminalis and coronary sinus. Patients underwent ablation of the pulmonary vein antrum (PVAI) only (n=45, group 1), PVAI extended to the entire scar areas (scar homogenization [n=66, group 2]) or PVAI plus ablation of non-PV triggers (n=66, group 3). Choice of ablation strategy was determined by the operator. Patients were followed up for arrhythmia recurrence with event recorders, ECG and Holter monitoring.

Results:
Baseline characteristics were not different between the groups (age 63±9 vs 58±10 vs. 60±11 years, p=0.23; male 71%, vs. 72% vs. 73% p= 0.91). After a single procedure, all patients were followed-up for a minimum of two years. The long-term success rate at the end of the follow up was 19% (12 pts) in group 1, 21% (14 pts) in group 2, and 61% (40 pts) in group 3. Kaplan-Meier log-rank test indicated that the cumulative probability of AF-free survival was significantly higher in group 3 (overall log-rank p <0.001, pairwise comparison 1 vs. 3 and 2 vs. 3 was significant at p<0.01).

Conclusions:
In patients with paroxysmal atrial fibrillation and severe left atrial scarring, PVAI plus ablation of non-PV triggers is associated with significantly better long-term outcome than PVAI alone or when PVAI is combined with scar homogenization.
Abstract 15754: The Prevalence of Electronic Health Record-Based Clinical Phenotypes in Patients With Pathogenetic Variants Associated With Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Haggerty Christopher M , Pendergrass Sarah A , Barr Marci , Leader Joseph B , Hartzel Dustin N , Ritchie Marylyn D , Carey David J , Ledbetter David H , Williams Marc S , Dewey Frederick E , Lopez Alexander , Penn John , Overton John D , Reid Jeffrey G , Murray Michael F , Fornwalt Brandon K
Published: July 2021

Objective
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare myocardial disorder. Genetic etiology is ascribed to variants in 8 genes (
PKP2
,
DSP
,
DSC2
,
DSG2
,
JUP
,
TMEM43
,
TGFβ2
,
RYR2
). We aimed to establish the prevalence and clinical phenotype of individuals with pathogenic variants (PV) in these genes from an unselected cohort.

Methods
Whole-exome sequences for 31,036 patients in the MyCode™ Biorepository were evaluated for pathogenic or likely pathogenic (P/LP) ARVC variants reported in ClinVar or the ARVC database. Composite ICD-9 data from the electronic health records of PV individuals vs a non-PV control group were analyzed.

Results
57 P/LP variants were identified in 240 individuals (0.77%), aged 61 ± 19 years. Characteristics of this PV group versus a non-PV control group are summarized in the table. Zero patients in the PV group had a documented diagnosis of ARVC. Use of implantable cardioverter defibrillators—the primary treatment for ARVC—was rare. Of individuals ≥55 years, 24% with PV had no history of cardiac disease (vs. 22% for non-PV). However, there was a modest increase in the prevalence of cardiac electrical abnormalities (e.g., tachycardia, fibrillation) in PV vs. non-PV. There was also a trend towards increased diagnoses of 'other primary cardiomyopathy'.

Conclusions
The prevalence of reported pathogenic ARVC variants (0.77%) greatly exceeds the disease prevalence (0.02 - 0.10%). In this cohort of 240 genotype-positive subjects, there was little evidence of overt ARVC disease, suggesting that the positive-predictive value for classic ARVC in individuals with an incidental positive genetic finding is low. The increased risk of certain clinical findings, not specific to ARVC, supports the notion that the spectrum of phenotypes associated with pathogenic variants in these genes is broader than classically described. Targeted “deep phenotyping” is needed to assess subclinical phenotypes in genomically screened populations.
Abstract 15760: Left Atrial Dysfunction in Patients With Anderson - Fabrys Disease Using Magnetic Resonance Imaging Derived Left Atrial Phasic Function
Authors: Calleja Anna M , Li Qin , Ng Ming-Yen , Deva Djeven P , Crean Andrew , Gruner Christiane , Iwanochko Mark , Thavendiranathan Paaladinesh
Published: July 2021

Background:
Anderson-Fabrys disease (AFD) is an x-linked lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase. This results in accumulation of globotriaosylceramide in various organs. The hallmark of cardiac involvement is left ventricular hypertrophy (LVH). However, autopsy studies have demonstrated involvement of the left atrium (LA) as well. There is currently limited data on left atrial volumes and function in patients with AFD. We sought to assess LA phasic volumes and function in patients with AFD using cardiac MRI (CMR) cine data.

Method and Results:
This was a retrospective study. Consecutive patients with clinically indicated CMR at our center were included. CMR acquired 2 and 4 chamber steady state free precession (SSFP) cine data were used to measure LA volume and phasic function with commercially available off-line software (eSieVVI, Siemens Medical System). We included 37 patients with AFD (18 males, mean age 48±13 yrs) and 22 age balanced healthy volunteers (8 males, mean age of 40±14 yrs). LA maximal and conduit volumes were not different between AFD and controls, but the LA minimal was larger (Table). Volume derived reservoir, conduit, and pump function were significantly reduced in AFD (Table). Strain measured reservoir and pump function were also significantly reduced in AFD. An inverse correlation was seen between LA reservoir strain and left ventricular (LV) mass (r=-0.53) and myocardial late gadolinium enhancement (LGE) measured using the 4 (r=-0.67) and 6 (r=-0.67) standard deviation thresholds.

Conclusion:
This is the first study to demonstrate abnormal LA function in patients with AFD using both volumetric and strain techniques. Patients with AFD had reduced LA reservoir and pump function with modest correlation with disease severity based on the burden of LV LGE and LV mass. Further studies are needed to assess the relationship between LA function and prognosis including the development of atrial arrhythmia.
Abstract 15762: Gapdh Interaction With Ape1 Endonuclease Protects Vascular Smooth Muscle Cells Against Apoptosis: Potential Role of These Enzymes in Prevention of Atherosclerotic Plaque Destabilization
Authors: Hou XW. , Yoshida T. , Higashi Y. , Shai SY , Kim C. , Delafontaine P. , Sukhanov S.
Published: July 2021

We have shown that oxidized lipids (OxLDL) co-localized with apoptotic vascular smooth muscle cells (VSMC) in atherosclerotic plaque and that OxLDL downregulated the major glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in cultured VSMC via H2O2-dependent mechanism. We hypothesized that maintenance of sufficient GAPDH levels is critical for cell survival under oxidative stress. H2O2 (220 uM, 12h) decreased GAPDH protein (55±5% decrease) and induced apoptosis (TUNEL assay) in human VSMC. Human VSMC transfection with pCMV-GAPDH increased GAPDH protein (3.5-fold) and prevented H2O2-induced apoptosis (74±4% decrease) vs. pCMV-GFP. We generated rat VSMC with constitutive 2-fold overexpression GAPDH (R3-VSMC). R3-VSMC had increased glycolysis (2.5 folds increase, pyruvate levels), ATP levels (38±2% increase) and reduced oxidative DNA damage (40±2% reduction in number of apurinic/apyrimidinic (AP) sites) and these effects correlated with suppressed H2O2-induced cell apoptosis (>90% reduction, TUNEL assay; 45.7±3.6% reduction, Cell Death ELISA). GAPDH-targeted siRNA reduced GAPDH protein (for 55%) and potentiated H2O2-induced apoptosis (9.4±0.3 folds increase, TUNEL; 8.6±0.4 folds increase, ELISA) in WT-VSMC and blocked anti-apoptotic effect seen in R3-VSMC.

GAPDH known to bind apurinic/apyrimidinic (AP) endonuclease 1 (APE1), a major DNA repair enzyme. We found that GAPDH was co-immunoprecipitated and co-localized with APE1 in cytosolic/nuclear fraction and H2O2 induced further GAPDH-Ape1 co-localization and migration toward nuclei. APE1 specific activity was increased in H2O2-treated R3-VSMC vs. H2O2-treated WT VSMC, suggesting that GAPDH preserved APE1 activity under oxidative stress. APE1-targeted siRNA abrogated the protection of GAPDH overexpression against H2O2-induced apoptosis in VMSC. In summary, GAPDH downregulation mediates oxidant-induced VSMC apoptosis and forced expression of GAPDH protects VSMC from H2O2-induced cell death potentially via activation of APE1-dependent DNA repair. Our data suggest that preservation of GAPDH and APE1 activity in plaque VSMC could be a potential strategy to stabilize plaque and prevent acute coronary events.
Abstract 15785: Long-term Cardiac Prognosis and Risk Stratification in 260 Adults Presenting With Mitochondrial Diseases
Authors: Wahbi Karim , Bougouin Wulfran , Bécane Henri Marc , Duboc Denis
Published: July 2021

Introduction:
The long-term cardiac prognosis of adults with mitochondrial diseases is unknown.

Methods and Results:
Between January 2000 and May 2014, we retrospectively included in this study 260 consecutive patients (60% women) ≥18 years of age, (interquartile range [IQR]; 31 to 54), with genetically proven mitochondrial diseases, including 109 with mitochondrial DNA (mtDNA) single large-scale deletions, 64 with the m.3243A>G mutation in
MT-TL1
, 51 with other mtDNA point mutations, and 36 patients with nuclear genes mutations. Cardiac involvement was present at baseline in 81 patients (30%). Single and multiple variable analyses were performed in search of predictors of major adverse cardiac event (MACE), and hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Over a median follow-up of 7 years [3.6 to 11.7], 27 patients (10%) suffered a MACE, defined as sudden death, death due to heart failure (HF), resuscitated cardiac arrest, 3
rd
degree atrioventricular block, sinus node dysfunction, cardiac transplantation, or hospitalization for management of HF. Patients with single large-scale mtDNA deletions or m.3243A>G mutations had the highest incidence of MACE. By multiple variable analysis, intraventricular conduction block (HR = 16.9; 95% CI: 7.2 to 39.4), diabetes (HR = 7.0; 95% CI: 2.9 to 16.7), premature ventricular complexes (HR = 3.6; 95% CI: 1.4 to 9.2) and left ventricular (LV) hypertrophy (HR = 2.5; 95% CI: 1.1 to 5.8) were independent predictors of MACE. In patients with 0, 1, and ≥2 risk factors, the incidence of MACE was 1.7, 15 and 42% respectively.

Conclusions:
Patients with mitochondrial diseases are at high risk of MACE, independently predicted by intraventricular conduction block, diabetes, ventricular prematurity and LV hypertrophy.
Abstract 15816: Normal Distribution of Wall Shear Stress in the Coronary Arteries
Authors: Starikov Anna , Xiong Guanglei , Min James K
Published: July 2021

Introduction:
The ability to detect hemodynamically significant coronary artery disease non-invasively has been a goal that has the potential to improve patient care significantly. New non-invasive approaches using coronary CT angiograms (CCTAs) have been proposed and appear to show some promise.

Hypothesis:
One such method is the measurement of measuring wall shear stress (WSS), the tangential force of flowing blood against the artery wall, using computational fluid dynamics (CFD). However, in order to deem this technique useful in clinical practice, the normal values must first be defined. These values have been minimally reported and are limited to the left coronary tree.

Methods:
We ran a CFD simulation of WSS on 3-D reconstructions of the coronary arteries derived from the CCTAs of 35 patients with either no disease or non-obstructive (< 50%) stenosis from the DeFACTO trial, a multi-center study. The resulting model was segmented according to the Society of Cardiovascular CT guidelines, separating the proximal and distal parts of each artery as well as the major side branches. The segments were composed of WSS values at hundreds of points along the vessel wall. The median value was taken as a representative of each segment.

Results:
The average values were calculated and varied significantly from one another, especially the proximal and distal parts of the same artery, as showing in Figure 1.

Conclusions:
These results establish the first known WSS distribution within all of the coronary arteries and serve as a foundation for defining a cut-off for abnormal values. Importantly, they also illuminate the variability of WSS that occurs even throughout a single artery and suggests that perhaps multiple abnormal cutoffs need to be established to evaluate WSS based on the location of the stenosis.
Abstract 15858: Does Switching to Proliferation Signal Inhibitors Decrease the Risk of Developing Subsequent Malignancies in Heart Transplant Patients?
Authors: Patel Jignesh , Kittleson Michelle , Siddiqui Saira , Liou Frank , Yabuno Jamie , Merchant Madeleine , Chang David H , Hamilton Michele , Czer Lawrence , Kobashigawa Jon A
Published: July 2021

Introduction:
Malignancy is vast approaching as the leading cause of death late after heart transplantation. It is known that the current immunosuppression regimen consisting of tacrolimus/cyclosporine and mycophenolate is associated with increased risk of cancers. The use of proliferation signal inhibitors (PSI) has been associated with less cancer development particularly in specific tumors. We sought to determine if there is an association of the use of PSI in decreasing overall cancer risk.

Methods:
Between 2004 and 2008 we assessed 16 heart transplant patients who were placed on PSI and compared cancer development based on conditional survival in the ensuing 5 years to those not on PSI (n=16). Patients were matched according to age, sex, time from transplant, and era.

Results:
Patients were switched to PSI on an average of 0.9 ± 0.9 years after transplant. Those patients that were placed on PSI had a higher subsequent 5-year actuarial freedom from cancer development compared to those patients not on PSI (100.0% vs 77.7%, p=0.049). These specific cancers included: skin cancer (2), squamous cell cancer (2), auricular carcinoma (1), prostate cancer (1), and cranial meningioma (1). There was no difference in 5-year actuarial freedom from cardiac allograft vasculopathy (CAV) development between the CNI + MMF/AZA and CNI + PSI groups (81.3% vs 72.2%,p=0.683).

Conclusions:
The use of PSI after heart transplantation appears to confer a protective effect against the development of malignancy. Larger number of patients are needed to confirm these observations.
Abstract 15892: Symptom Diary Use Improves Outcomes for Heart Failure Patients
Authors: Park Linda G , Dracup Kathleen , Whooley Mary A , Pelter Michele M , Moser Debra K , Biddle Martha , Clark Robyn A , Howie-Esquivel Jill
Published: July 2021

Introduction:
Attention to symptoms of weight gain and dyspnea are central tenets in heart failure (HF) patient education. Daily diary use can be one method for HF patients to acknowledge and attend to their symptoms. However, it is not known whether diary use improves patient outcomes. We aimed to compare mortality among rural HF patients who did versus did not complete a daily diary of weight and symptom self-assessment.

Methods:
This study was a secondary analysis of a 3-arm randomized controlled trial with two intervention groups (Fluid Watchers LITE and PLUS) and usual care. The two intervention groups were given daily diaries for 2 years to track daily weight, HF symptoms, and response to symptom changes. Intervention group patients received self-care education and a script to call their health care provider, but the 2 groups varied on the number of follow-up phone calls received. Patient groups were categorized by duration of adherence to diary use: None, Low (1-3 months), Medium (4-12 months), and High (13-24 months). Cox regression analysis assessed survival from cardiac and non-cardiac death for 2 years while controlling for age and depression.

Results:
The mean age was 66 ± 13, 58% (n=227) were male, and 67% (264/393) completed diaries with no difference in diary use between the 2 intervention groups. As compared with the 129 patients with no diary use, the 117 patients with High diary use had fewer non-cardiac (p=0.001) and cardiac (p=0.01) deaths; the 89 patients with Medium diary use had fewer non-cardiac deaths (p=0.007) but similar cardiac deaths (p=0.79).

Conclusions:
This is the largest trial to examine daily diary use in HF patients over 2 years. Improved non-cardiac survival was associated with at least 4 months of diary use, while cardiac survival was associated with at least 12 months of diary use. It is unclear why non-cardiac survival improved, but it is speculated that attention to cardiac symptoms may have increased attention to non-cardiac symptoms.
Abstract 15894: Adaptations of Innate Immunity in Hibernation: Mechanisms for Protection Against Acute Organ Injury
Authors: Quinones Quintin J , Ma Qing , Smith Michael P , Staats Janet , Chan Cliburn , Barnes Brian M , Podgoreanu Mihai V
Published: July 2021

Introduction:
Hibernation is a natural molecular adaptation to extreme environmental conditions with important implications for perioperative organ protection.

Hypothesis:
We hypothesized that the hibernator cardioprotective phenotype is accompanied by altered expression of innate immune pattern-recognition receptors (PRRs) and inflammatory pathways.

Methods:
LV myocardium, peripheral blood monocytes (PBMC), and plasma were collected from rat, summer AGS, and winter AGS after sham, 3h or 24h ischemia/reperfusion (I/R).

Results:
Plasma troponin I detection confirmed greater I/R injury in rat compared to AGS (Fig 1). Proteomic profiling of LV myocardium detected multiple differences including higher expression of MyD88 dependent toll-like receptors (TLR) in rat compared to AGS; average levels of TLRs were 1.8 fold higher in rat compared with hibernating AGS. Comparison of PBMCs from rat, summer, and hibernating AGS revealed increased PRR expression and cytokine production in the rat compared to the AGS, along the TLR3/TICAM (Fig2), TLR/MyD88, and AIM2/inflammasome axes.

Conclusions:
Compared to AGS, rats experience robust inflammasome activation in response to I/R as evidenced by >30-fold increases in AIM2 and Caspase 1. Hibernation state differences in innate immunity exist, including reduced expression of PRRs(TLR1,3, and AIM2); additionally signaling via TLR 3 and 4 is greatly dampened in winter AGS due to nearly absent expression of TICAM1. Circulating immune effector cells in winter AGS have an abrogated response to DAMPs compared to cells from summer AGS or rat, as evidenced by reduced cytokine production.
Abstract 15901: Radiofrequency Ablation for Persistent Atrial Fibrillation: Earlier Catheter-based Interventions are associated With Better Outcomes and in Direct Association With Markers of Pathways of Atrial Remodeling
Authors: Barakat Amr F , Hussein Ayman A , Bassiouny Mohammed , Hakim Ali , Al Halabi Shadi , Tarakji Khaldoun , Baranowski Bryan , Cantillon Daniel , Dresing Thomas , Tchou Patrick , Martin David O , Varma Niraj , Bhargava Mandeep , Callahan Thomas , Niebauer Mark , Kanj Mohamed , Chung Mina , Saliba Walid I , Natale Andrea , Lindsay Bruce D , Wazni Oussama M
Published: July 2021

Introduction:
Persistent atrial fibrillation (PerAF) ablation has been associated with significant recurrence rates which could reflect progressive AF-related atrial remodeling. We hypothesized that the first-diagnosis to ablation time for PerAF is a major determinant of success rates and in direct association with pathways of atrial remodeling.

Methods:
Two-year outcomes were assessed in 1241 patients undergoing first time ablation of PerAF between January 2005 and December 2012 at our institution. The time intervals between the first diagnosis of PerF and the ablation procedures were determined. Patients had echocardiograms and measures of B-type natriuretic peptide (BNP) and C-reactive protein (CRP) before the ablation procedures. During ablations, patients with atrial scarring by voltage were identified.

Results:
The median time-to-ablation since the first PerAF diagnosis was 3 years (interquartile range 1-6.5). With longer diagnosis-to-ablation time (based on quartiles), there was a significant increase in BNP levels (p=0.01), CRP levels (p<0.0001), left atrial size (p=0.03) and scarring (p=0.04). Atrial arrhythmia recurred after a single ablation in 555 patients (44.7%); and 364 (29.3%) underwent repeat ablations. At last follow-up, 1005 patients (81.0%, 390 on antiarrhythmic medications) were either arrhythmia free or had their arrhythmia controlled. In Cox Proportional Hazard analyzes, BNP levels, CRP levels, left atrial size and scarring were associated with arrhythmia recurrence. The diagnosis-to-ablation time had the strongest association with success rates which persisted in multivariate Cox analyzes (HR for recurrence per +1Log diagnosis-to-ablation time 1.25, 95%CI 1.11-1.42, p<0.0001; 4th vs. 1st quartile 2.27, 95%CI 1.52-3.47, p<0.0001).

Conclusions:
The success rates with PerAF ablation are highest with early intervention, that is ablation before the progression of atrial remodeling.