bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16417: Resuscitative Endovascular Balloon Occlusion of the Aorta Improves Hemodynamics and Return of Spontaneous Circulation When Combined With Standard Closed Chest Compressions in a Swine Model of Traumatic Cardiac Arrest
Authors: Anderson Kenton L , Morgan Jeffrey D , Castenada Maria G , Boudreau Susan M , Bebarta Vikhyat S
Published: March 2022

Introduction:
Recent evidence has demonstrated that closed chest compressions (CC) directly over the left ventricle (LV) during traumatic cardiopulmonary arrest (TCPA) improve hemodynamics and return of spontaneous circulation (ROSC) when compared to standard chest compressions. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is also able to improve hemodynamics as well as control hemorrhage during TCPA.

Hypothesis:
We hypothesized that the combination of REBOA and closed chest compressions located over the LV would result in improved hemodynamics and ROSC in a swine model of TCPA.

Methods:
Transthoracic echo was used to mark the location of the aortic root and the center of the left ventricle on animals (n=52) which were randomized to receive chest compressions in one of the two locations. Half the animals in each group received REBOA placement so there were four arms. One third of each animal’s blood volume was removed and ventricular fibrillation (VF) was induced to simulate traumatic cardiac arrest. After a period of ten minutes of VF, basic life support (BLS) with mechanical CPR was initiated and performed for ten minutes followed by advanced cardiac life support (ACLS) and blood transfusion for an additional ten minutes. Animals with REBOA had the balloon inflated at minute 6 of BLS. Hemodynamic variables were averaged every two minutes.

Results:
ROSC increased among standard CC animals with REBOA (33%) compared to standard CC animals without REBOA (0.0%) (p=0.04). Among standard CC animals, aortic systolic blood pressure, right atrial systolic blood pressure and end tidal CO2 (ETCO2) increased during all time intervals of BLS (p<0.005) with REBOA. ETCO2 also increased during BLS among LV CC animals with REBOA compared to LV CC animals without REBOA (p≤0.0001), however, ROSC and other hemodynamics were not significantly different. There was no difference in ROSC or hemodynamics between the LV CC and standard CC groups with REBOA.

Conclusions:
In our swine model of TCPA, ROSC and hemodynamics are improved among animals receiving standard closed chest compressions, however, there is no additional benefit with REBOA if compressions are performed over the LV.
Abstract 16418: Reinitiation of Antithrombotic Therapy After Emergency Procedures or After an Uncontrolled or Life Threatening Bleeding Event. Initial Experience From the Re-verse Ad Trial
Authors: Pollack, Jr. Charles V , Reilly Paul A , Eikelboom John , Glund Stephan , Verhamme Peter , Bernstein Richard A , Dubiel Robert , Huisman Menno V , Hylek Elaine , Kamphuisen Pieter W , Kreuzer Jörg , Levy Jerrold H , Sellke Frank , Stangier Joachim , Steiner Thorsten , Wang Bushi , Kam Chak-Wah , Weitz Jeffrey I
Published: March 2022

Background:
In AF patients, oral anticoagulation is effective for stroke risk reduction, but there is uncertainty on how to manage re-initiation of anticoagulation after a bleeding complication. Ideally, therapy would be stopped immediately and reinitiated as soon as possible after the bleeding has resolved. In clinical trials comparing dabigatran to warfarin, urgent interventions were linked to higher rates of both bleeding and thromboembolic events than elective interventions. Idarucizumab immediately reverses the anticoagulant effects of dabigatran without prothrombotic effect. Due to idarucizumab’s specificity to dabigatran, other drug-drug interaction is not expected, allowing the clinician flexibility in managing antithrombotic therapy during and after the event.

Methods:
In the ongoing phase III RE-VERSE AD study, dabigatran-treated patients with uncontrolled bleeding (Group A) or who require emergency surgery (Group B) are given 5 g of idarucizumab IV. The primary endpoint was median maximum reversal of the anticoagulant effect of dabigatran, based on dilute thrombin time (dTT) or ecarin clotting time (ECT) within 4 h of study drug infusion. Data collection on re-initiation of antithrombotic therapy was studied as a secondary endpoint.

Results:
In the interim analysis of 90 patients, median maximum reversal of the anticoagulant effect of dabigatran was 100%. For antithrombotic re-initiation data, see Table.

Conclusions:
Idarucizumab is an immediate-acting, specific reversal agent for dabigatran. Preliminary results from RE-VERSE AD suggest that idarucizumab facilitates the periprocedural management of dabigatran-treated patients. Of note is that after an acute event, alternative antithrombotic therapy can be initiated at any time after idarucizumab application. Reintroduction of dabigatran was possible as early as 24 h after idarucizumab treatment. This is desirable to protect patients from their underlying thromboembolic risk.
Abstract 16423: Functional Outcomes of Adult Extracorporeal Membrane Oxygenation Survivors
Authors: McCarthy Fenton H , McDermott Katherine M , George Justin , Kim Jennifer , Hoedt Ashley C , Wald Joyce W , Szeto Wilson Y , Atluri Pavan , Vallabhajosyula Prashanth , Gutsche Jacob T , Acker Michael A , Desai Nimesh D
Published: March 2022

Objectives:
Little is known regarding the functional outcomes of ECMO survivors and the health-related quality of life comparing Arterio-Venous (AV) versus Veno-Venous (VV) ECMO survivors in the current era.

Methods:
All adults who underwent AV or VV ECMO from 2007 to 2014 and were subsequently discharged alive at a single institution between were surveyed. The survey included the validated SF-36 and EQ-5D-5L questionnaires, and ECMO related outcomes.

Results:
We surveyed 64 patients including 44 AV and 20 VV ECMO survivors. Patients were discharged home in 59% of cases and to a rehab or another healthcare facility in 41% of cases. One-year survival was 93%. Responses were obtained from 33 patients (54% response rate), including 21 AV survivors and 12 VV survivors. The average age was 46.2 ± 14.6 years. VV ECMO survivors were supported for a longer period of time compared to AV ECMO survivors (10 ± 8.6 days v. 4.71 ± 5.5 days, p = 0.02). AV ECMO survivors had a significantly higher Mental Composite Summary (MCS) compared to VV ECMO survivors (50.4 ± 8.2 v 43.16 ± 10.9, p=0.04). There were no other significant differences in the SF-36 or the EQ-5D-5L scores (Table 1, Figure 1). Of surveyed patients, 41% continue to work and 32% work at their same pre-ECMO job. Rehospitalization occurred in 59% of patients. Only 34% of surviving patients had living wills, with just two patients requesting no mechanical ventilation or ECMO.

Conclusions:
Functional outcomes among ECMO survivors are generally high and similar between AV and VV ECMO survivors. VV ECMO survivors demonstrated perhaps some areas of lower health-related quality of life with lower SF-36 scores on the Mental Composite Summary.
Abstract 16466: Total Number of Pregnancies and Atrial Fibrillation Risk: The Women’s Health Study
Authors: Wong Jorge A , Rexrode Kathryn M , Sandhu Roopinder K , Conen David , Albert Christine M
Published: March 2022

Introduction:
Parity has been associated with an increased risk of cardiovascular disease (CVD), which is thought to be mediated by obesity and insulin resistance. However, the relationship between parity and atrial fibrillation (AF) remains unclear.

Methods:
We examined 34,636 female health professionals aged ≥45 years and free of AF or CVD at baseline within the Women’s Health Study. Women were prospectively followed for development of new-onset AF, which was confirmed by medical record review. Cox proportional hazards models were used to evaluate the relationship between total number of pregnancies ≥6 months in duration (0-1 [referent], 2-3, 4-5, 6) and incident AF risk.

Results:
During a median follow-up of 19.2 years, 1467 women developed incident AF. Median baseline age was 52.9 [IQR 48.9, 58.8] years. In multivariable analyses (Table), after adjustment for multiple confounders, including measures of socioeconomic status, hazard ratios (HR) and 95% confidence intervals (95%CI) for incident AF across categories of increasing total number of pregnancies were 1.0, 1.12 (0.94 - 1.33), 1.26 (1.04 - 1.53), and 1.37 (1.06 - 1.76). Further adjustment for time-updated changes in body mass index (BMI), hypertension, diabetes, hypercholesterolemia and other variables did not have a significant impact on these associations. Adjustment for CVD events occurring during follow-up did not significantly alter these results (fully adjusted HRs and 95%CIs across pregnancy categories: 1.0, 1.11 (0.93 - 1.32), 1.25 (1.03 - 1.52), 1.35 (1.05- 1.74); p for linear trend=0.005).

Conclusions:
In this large prospective cohort, number of prior pregnancies was directly associated with subsequent AF risk among women over age 45. This risk was not mediated by non-fatal CVD events, obesity, and/or diabetes. Repeated exposure to metabolic, physiological and/or hormonal changes during pregnancy may predispose to AF in later life and requires further investigation.
Abstract 16485: Hyperinsulinemia Reduces Autophagy in Insulin Resistant Hearts Through Insulin Growth Factor 1 Receptor (IGF-1R) Signaling
Authors: Pires Karla Maria , Buffolo Marcio Augusto , Pei Shaobo , Sloan Crystal , Henrie Brandon , Boudina Sihem
Published: March 2022

Introduction:
Diabetes is a leading cause of mortality and morbidity worldwide with over 50% of deaths in diabetic patients being caused by cardiovascular complications. The mechanisms underlying the high incidence of diabetic cardiac dysfunction remain relatively obscure but may involve altered autophagy. Macro-autophagy (referred to as autophagy) is a regulated intracellular catabolic pathway for the turnover of long-lived proteins, macromolecular aggregates, and damaged organelles.

Hypothesis:
Taking advantage TIRKO mice (a mouse model of total cardiac ablation of insulin receptors [IRs]), we aimed to investigate the impact of myocardial insulin resistance and systemic hyperinsulinemia (SH) on cardiac autophagy.

Results:
Basal and fasting-induced autophagy were significantly reduced in TIRKO hearts, as evidenced by reduced LC3II/LC3I ratios and increased P62 accumulation. As TIRKO mice develop SH, we next sought to determine whether this reduces autophagy independently of the absence of IRs. Thus, we used mice with cardiomyocytes-specific deletion of IRs (CIRKO mice) but without SH or (ob/ob) mice that have IRs in the heart but develop SH. We demonstrated that cardiac autophagy reduction is indeed caused by systemic SH as its level was unaltered in CIRKO hearts but reduced in (ob/ob) hearts. Because of the absence of IRs in TIRKO hearts and the degree of insulin resistance in (ob/ob) hearts, we hypothesized that the reduction of cardiac autophagy by SH is mediated by the IGF-1R signaling. Indeed, IGF-1R phosphorylation was enhanced in both TIRKO and (ob/ob) hearts but not in CIRKO hearts. To begin to understand the functional role of attenuated autophagy in TIRKO hearts, we further decreased autophagosomes clearance by treating mice with the lysosomal clearance inhibitor chloroquine. Treatment of TIRKO mice with chloroquine for 4 hours massively increased LC3I and P62 levels, promoted cells death and decreased mitochondrial clearance.

Conclusions:
Taken together, these results suggest that hyperinsulinemia-mediated reduction in cardiac autophagy can be adaptive to suppress sustained autophagy activation by insulin resistance but can become maladaptive if the heart is challenged by a reduction in lysosomal degradation.
Abstract 16492: Spatiotemporal AED Location Optimization
Authors: Chan Timothy C , Sun Christopher L , Demirtas Derya , Morrison Laurie J , Brooks Steven C
Published: March 2022

Background:
Mathematical optimization can be used to plan future AED placement to maximize out-of-hospital cardiac arrest (OHCA) coverage. Many public access AEDs are placed in locations without 24/7 access. AED coverage can be overestimated unless temporal availability is considered.

Objective:
To develop a new spatiotemporal AED location optimization model that accounts for both spatial and temporal information.

Methods:
We identified all atraumatic public-location OHCAs occurring in Toronto, Canada from Jan. 2006 – Aug. 2014. We gathered location and operating hours data for 4898 buildings that were used as potential sites for AED placement. We extended a previously published spatial optimization model, which identifies locations to place AEDs that maximize the number of historical OHCAs occurring within 100 m of an AED. The new spatiotemporal model finds AED locations that maximize the number of OHCAs occurring within 100 m of an available AED, considering when the OHCAs occurred (“actual coverage”). We then compared the spatial and spatiotemporal models on actual coverage of out-of-sample OHCAs using 10-fold cross validation. Statistical analysis was performed using McNemar’s test.

Results:
We identified 2440 atraumatic public-location OHCAs. AED locations chosen by the spatiotemporal model outperformed those chosen by the spatial model by 26.1% in actual coverage (p<0.001). The figure shows coverage improvement at all times of day: daytime (11.2%), evening (37.4%), and night (292.3%). Equivalently, 40.2% fewer AEDs are needed when using the spatiotemporal model to reach the same level of actual coverage provided by AEDs located according to the spatial model.

Conclusion:
Spatiotemporal optimization can maximize actual OHCA coverage by accounting for AED availability when identifying future AED locations. The largest gains occurred during the evening and night, which is when the largest coverage losses were experienced by Toronto’s existing AEDs.
Abstract 16529: Molecular and Functional Characterization of an Ultra Rare Frame-shift Mutation in CALR-encoded Calreticulin as a Probable Long QT Syndrome-susceptibility Variant
Authors: Gibbs Christopher M
Published: March 2022

Introduction:
Long QT syndrome (LQTS) is the most common, autosomal dominant, sudden death predisposing cardiac channelopathy. Although 17 LQTS genes have been discovered, 20% of LQTS remains genetically elusive. Whole exome sequencing (WES) followed by a strategic, knowledge-based variant filtration approach may elucidate novel LQTS-susceptibility genes.

Methods:
A LQTS family with multiple sudden deaths was referred for genetic evaluation. The index case was a 21-year-old male who died suddenly but had a pre-mortem ECG with marked QT prolongation. The decedent’s mother also showed QT prolongation. Only paraffin embedded tissue (PET) was available from the decedent, so the mother’s DNA was analyzed by WES. Following WES, variants were filtered using Ingenuity Variant Analysis (IVA) software. Only non-synonymous variants with a quality score >20, read-depth >10, and absent in ExAC were considered. Further filtration was performed using IVA’s biological context pathway analysis set to capture genes most likely related to LQTS. Electrophysiological studies were performed on the variant with highest probability of pathogenicity.

Results:
Following WES and variant filtration, only a CALR frame-shift variant (R376fs/10) remained as a probable LQTS mutation. No radical CALR variants reside in ExAC’s 60,000+ exomes. The mutation was confirmed in the decedent’s PET-derived DNA. CALR-encoded calreticulin (CRT) is a Ca2+ binding chaperone of the endoplasmic reticulum. Both knockout and over-expression of CRT exert extreme effects on the murine cardiac system, including sudden death. Recently, CRT has been linked with altered L-type calcium (LTCC) ion channel activity. Wild-type (WT)-CALR reduced Cav1.2 peak current density by 43.1%. In contrast, CALR-R376fs/10 mutation reversed this Cav1.2 inhibition and caused a net gain-of-function of Cav1.2 channel current compared with CALR-WT co-expression (64.2% increase). No pathogenic variants in CALR were identified in 25 additional, unrelated, genetically elusive LQTS cases.

Conclusion:
Mutations in CALR-encoded calreticulin may be a rare cause of autosomal dominant LQTS precipitated in part by an accentuation of the LTCC, thereby potentially mimicking CACNA1C-mediated LQTS.
Abstract 16562: Cardiac Device Implantation Post TAVR: Mortality and Rates of Pacemaker Dependency
Authors: Padmanabhan Deepak , Eleid Mackram , Deshmukh Abhishek , Scott Christopher , Mcleod Christopher , Cha Yong-Mei M , Asirvatham Samuel P , Friedman Paul , Greason, Kevin L , Gulati Rajiv M , Noseworthy, Peter A. M
Published: March 2022

Background:
Transcatheter aortic valve replacement (TAVR) is often complicated by AV block requiring pacing, but whether patients recover AV conduction and whether the need for pacing affects outcomes is unknown.

Methods:
We retrospectively studied 534 patients who underwent TAVR at Mayo Clinic in Rochester, Minnesota between November 2008 and January 2015. Of these, 115 patients had implantable cardiac devices. Data was collected from subsequent device follow-ups to determine pacemaker dependency and percentage pacing.

Results:
44 patients (8.2%) had devices implanted in the immediate post procedural period. The most common indications for implantation were high grade AV block (18 patients) and complete heart block (14 patients). 17/44 (38.6%) patients were pacemaker-dependent at implant and only 4 of these patients were no longer pacemaker-dependent during subsequent followup. The indication for pacing among these four patients was high grade atrio-ventricular block (2 patients), asystole (1 patient) and complete heart block (1). Among non-pacemaker-dependent patients, no significant change in the ventricular pacing percentages was noted over time. Survival was similar between patients who required device implantation post TAVR and those who did not after adjustment for age and gender (HR 0.73 [0.39-1.36], p=ns; figure)

Conclusion:
Patients requiring pacing after TAVR are often pacemaker-dependent at the time of implant. It is uncommon for patients who are dependent at the time of implant to regain AV conduction, but the need for cardiac pacing is not associated with increased mortality.
Abstract 16587: Tpeak-to-tend Interval Corrected for Heart Rate: A More Precise Measure of Increased Sudden Death Risk?
Authors: Chua Kelvin C , Uy-Evanado Audrey , Teodorescu Carmen , Reinier Kyndaron , Chugh Harpriya , Narayanan Kumar , Gunson Karen , Jui Jonathan , Chugh Sumeet S
Published: March 2022

Introduction:
The Tpeak-to-Tend interval (Tpe) on the 12-lead electrocardiogram (ECG) predicts increased risk of sudden cardiac death (SCD). There has been some controversy on whether Tpe would be more useful if corrected for heart rate (Tpec).

Hypothesis:
We hypothesize that correcting the Tpe for heart rate will improve its predictive value for SCD.

Methods:
Cases of sudden cardiac death (SCD) (n=725; mean age 67.4 years; 95% CI 52.7 to 82.1 years; 67.7% males) from a large ongoing population based study of SCD in the Northwest US (population approx. one million) with an ECG available prior and unrelated to the SCD event were analyzed. Comparisons were made to control subjects with and without coronary artery disease (n=898; mean age 66.9 years; 95% CI 55.5 to 78.3 years; 63.7% males). The Tpe interval was corrected for heart rate using the Bazett (TpecBa) and Fridericia (TpecFd) formulae and the predictive value of Tpec for SCD was compared in logistic regression models.

Results:
The area-under-curve (AUC) for predicting SCD improved with both correction formulae, TpecBa at 0.628 and TpecFd at 0.606 compared to an uncorrected Tpe at 0.544 (see Figure). The optimal cut-off value for TpecBa and TpecFd was determined using the receiver-operating characteristics (ROC) curve. A TpecBa of more than 94ms and TpecFd of more than 88ms was predictive of SCD independent of age, gender, comorbidities (hypertension, diabetes mellitus, previous myocardial infarction), electrocardiographic left ventricular hypertrophy (LVH), severe left ventricular dysfunction (LVEF ≤35%), prolonged QTc (>450ms) and prolonged QRS duration (>120ms) with an odds ratio of 1.88 (95% CI, 1.36 to 2.60; p <0.0001) and 1.90 (95% CI, 1.38 to 2.62; p <0.0001) respectively.

Conclusion:
Correcting the Tpeak-to-Tend interval for heart rate, using either the Bazett and Fridericia formulae, improved the independent predictive value of this marker for assessment of SCD risk in the community.
Abstract 16596: Disruption of Gravin’s Scaffolding as a Potential Therapy for Heart Failure in Combination With Carvedilol
Authors: Singh Sonal , Suryavanshi Santosh , Fa'ak Faisal , Diaz Diaz Andrea , McConnell Bradley
Published: March 2022

Beta-adrenergic receptor (β-AR) desensitization culminating in impaired β-AR signaling triggers the vicious cascade of HF. Gravin; an A-kinase anchoring protein (AKAP) is crucial for desensitization of the β-ARs upon agonist stimulation. Our previous studies have shown that disruption of gravin’s scaffolding imparts protection against isoproterenol induced HF in mice. The goal of this study was to further compare the protective effects of absence of gravin in HF to that of the standard β blocker HF therapy such as Carvedilol and Bisoprolol. After inducing HF with 2-weeks administration of isoproterenol (60mg/kg/day), wild-type (WT) and gravin-t/t mice (harboring non-functional truncated gravin) were started on blocker therapy. There was no significant reduction in the HW/BW ratio or the fibrotic lesions after Carvedilol and Bisoprolol treatment in the WT mice; whereas, gravin-t/t mice did not show any significant increase in either of the two after isoproterenol treatment. Gravin-t/t mice treated with either of these blockers showed enhanced hemodynamic function compared to the WT mice on the blocker therapy. Interestingly, the gravin-t/t mice after treatment with Carvedilol showed significant increase in the β2-AR expression (579.83 ± 0. 476 fmol/mg) compared to the WT mice (113.74 ± 0. 359 fmol/mg) treated with Carvedilol; whereas, no significant changes were observed in the β1-AR expression in WT (310.03 ± 0. 284 fmol/mg) or gravin-t/t mice (282.54 ± 0. 392 fmol/mg). Bisoprolol treatment on the other hand showed significant increase only in the β1-AR expression post treatment for both WT (405.62 ± 0. 264 fmol/mg) and gravin-t/t (421.01 ± 0. 382 fmol/mg) mice. Though Carvedilol is the gold standard for HF, and it increases the contractile function of the failing heart, it does not rescue the decline in the receptor density. Absence of gravin not only increases the β2-AR expression 2-fold at baseline but also increases it 5-fold after Carvedilol treatment. Disruption of gravin’s scaffolding is a potential drug target and can be further developed as a combination therapy with Carvedilol. Increase in β2-ARs expression can provide beneficial effects via activation of anti-apoptotic and survival pathways.
Abstract 16597: Economic Evaluations of PCSK9 Inhibitors in Reducing Cardiovascular Risk From Societal & United States Payer Perspective
Authors: Nasir Khurram , Arrieta Alejandro , Veledar Emir
Published: March 2022

Introduction:
We aim to evaluate cost-effectiveness of recent FDA advisory committee recommended PCSK9 inhibitors for reducing cardiovascular disease (CVD) risk from societal & U.S. third-party payer perspective.

Methods:
A Markov model was used to evaluate costs and effects associated with addition of PCSK9 inhibitor to standard of care (SOC) based on a) estimated 53% 1-year relative risk reduction (SOC 1 year CVD event rate: 2.18%, PCSK9 inhibitor+SOC: 0.95%), b) indirect annual CVD reduction probability (using Framingham risk) via mean 61% LDL lowering among at CV risk patients. The model considers cycles of 1 year. Post CVD events last 5 years, after that time individuals go back to treatment state if no subsequent CVD observed. Health state costs were derived from published evidence. Survival probabilities >1 year were transformed to annual probabilities assumed on survival models. From societal perspective, cost per Quality-Adjusted Life Years (QALYs) gained are presented. We estimated payer’s perspective on net benefit balancing treatment vs. avoided cost and premium revenues over patient lifespan.

Results:
The table highlights societal gains and payer’s net benefit across range of estimated annual drug cost. At willingness-to-pay threshold of $100,000/QALY, PCSK9 inhibitors appear cost-effective if priced annually at $2500. At annual cost of $10,000, cost/QALY gained with PCSK9 inhibitor is nearly $400,000. From payer’s perspective, approximate net benefit was -$11,000 to -$51,000 per patient treated across annual drug cost range. Net benefits were only positive if treatment priced around $500/year.

Conclusion:
This study provides insights to facilitate discussion among healthcare stakeholders for considering future PCSK9 inhibitor’s utility balancing estimated benefits while accounting need for additional financial resources. Gaps between social & private benefits need to be aligned for appropriate PCSK9 inhibitors adoption in U.S.
Abstract 16611: Impact of Mechanical Unloading on Structural and Non-structural Components of the Extracellular Matrix in Patients With Dilated Cardiomyopathy
Authors: Sakamuri Siva S , Takawale Abhijit , Bas Ratnadeep , Wang Xiuhua , Fedak Paul W , Freed Darren H , Oudit Gavin Y , Kassiri Zamaneh
Published: March 2022

Introduction:
Extracellular matrix (ECM) is the non-cellular component of the myocardium and its remodeling in cardiomyopathy is a major contributor to disease outcomes. While the impact of left ventricular assist device (LVAD) on remodeling of fibrillar ECM has been studied, its effects on the non-fibrillar ECM and matricellular proteins within the ECM that can influence cardiac structure and function are unknown.

Hypothesis:
Mechanical unloading preserves the non-fibrillar ECM composition, thereby contributing to reversal of adverse myocardial remodeling.

Methods:
Hearts were obtained from heart failure patients with idiopathic dilated cardiomyopathy (DCM) with LVAD support (>3mths; LVAD), without LVAD (no-LVAD), and non-failing control hearts (NFC) (n=10/group). LV free wall were fixed or flash-frozen for molecular and IHC evaluations.

Results:
Assessment of fibrillar ECM showed greater total and insoluble collagen content in no-LVAD hearts, consistent with an increase in collagen type I mRNA, and collagen type I-to-type III ratio. Proteolytic activities (collagenase & gelatinase) were significantly higher in no-LVAD (by 45% and 40%) suggesting greater ECM turnover in these hearts. TIMP1 mRNA decreased in both DCM groups (by 60%), but its protein decreased only in no-LVAD hearts (by 30%). TIMP3 and TIMP4 mRNA (by 30% and 55%) and protein (by 60% and 55%) decreased in both LVAD and no-LVAD hearts. ADAM-TS2, the N-terminal endopeptidase for collagen, was markedly lower in no-LVAD, while LOX1, the cross-linking enzyme showed a small increase in no-LVAD hearts. Evaluation of the basement membrane revealed that laminin arrangements were dispersed in no-LVAD hearts. Integrin β1, a cardiomyocyte cell-surface receptor for laminin, was reduced in no-LVAD but preserved in LVAD hearts. Other basement membrane proteins (fibronectin-1, collagen IV) showed similar trends, whereas differences in matricellular proteins (osteopontin, SPARC) were less striking between LVAD and no-LVAD hearts.

Conclusions:
Mechanical unloading positively impacts multiple aspects of myocardial ECM, the fibrillar ECM network and the less explored basement membrane, although the matricellular proteins residing within the ECM seem to be less affected.
Abstract 16646: Invasive Assessment of Myocardial Bridging in Women and Men Presenting With Angina in the Absence of Obstructive Coronary Artery Disease
Authors: Pargaonkar Vedant S , Schnittger Ingela , Tanaka Shigemitsu , Yamada Ryotaro , Kimura Takumi , Rogers Ian , Tremmel Jennifer A
Published: March 2022

Introduction:
Up to 20% of patients with angina undergoing coronary angiography have no obstructive coronary artery disease (CAD). Myocardial bridging, while common in the population, is a potential cause of angina in this subset of patients.

Hypothesis:
We studied sex differences in the structural and hemodynamic characteristics of myocardial bridging in patients with angina in the absence of obstructive CAD.

Methods:
We identified a myocardial bridge (MB) in the left anterior descending artery by intravascular ultrasound (IVUS) in 62 women and 24 men with angina in the absence of obstructive CAD. A MB was defined as an echolucent half-moon sign and/or ≥10% systolic compression. We evaluated MB-related parameters, including total MB length, % arterial compression, and halo thickness, as well as minimum lumen area and plaque burden. Hemodynamic testing of the MB was performed using an intracoronary pressure/Doppler flow wire at rest and during dobutamine stress. We calculated diastolic fractional flow reserve (dFFR) (the ratio of diastolic intracoronary pressure divided by aortic pressure), as well as peak Doppler flow velocity. An abnormal dFFR was defined as ≤0.76 during dobutamine stress.

Results:
When compared with women, men had a longer length of myocardial bridging, more systolic compression, and a greater plaque burden proximal to the MB. There was no difference in halo thickness or MLA. There was also no sex difference in the dFFR or peak Doppler velocity change with stress (figure).

Conclusions:
While women are more likely than men to have angina in the absence of obstructive CAD, in patients with a MB as a possible cause of their angina, men have a longer length of bridge, more systolic compression, and greater plaque burden proximal to the MB than women. Interestingly, these more severe MB features in men do not result in more hemodynamic significance. Further research is needed to understand this sex difference.
Abstract 16653: Clinical Outcome and Short-term Follow up After Surgical Unroofing of a Myocardial Bridge in Patients With Angina and No Obstructive Coronary Artery Disease
Authors: Pargaonkar Vedant S , Schnittger Ingela , Tremmel Jennifer A , Rogers Ian , Tanaka Shigemitsu , Yamada Ryotaro , Kimura Takumi , Fischbein Michael , Mitchell R Scott , Boyd Jack
Published: March 2022

Introduction:
Although a myocardial bridge (MB) is a common, generally benign anatomic variant, a small subset of patients experience severe anginal symptoms related to their MB, resulting in significant physical limitations and a poor quality of life. Surgical unroofing (supra-arterial myotomy) is a treatment option when medical management fails, but little is known regarding the clinical outcomes of patients who undergo surgical unroofing.

Methods:
A total of 34 patients (10 men, 24 women) with severe angina and a hemodynamically significant MB underwent surgical unroofing. All patients had failed medical management and had undergone extensive testing prior to surgery, including exercise echocardiography, coronary computerized tomography angiography, invasive coronary angiography, intravascular ultrasound (a MB was defined as an echolucent half-moon sign and/or ≥10% systolic compression), and hemodynamic testing using an intracoronary pressure and Doppler flow wire at rest and during dobutamine stress to calculate a diastolic fractional flow reserve (dFFR) (the ratio of diastolic intracoronary pressure divided by aortic pressure), as well as the peak Doppler flow velocity. An abnormal dFFR was defined as ≤0.76 during dobutamine stress. A Seattle angina questionnaire (SAQ) was administered to evaluate symptoms and quality of life before and after surgery.

Results:
The mean age was 45.1 ± 15.7 years and median follow-up was 6.6 (2 - 13) months after surgery. There were no major complications during the pre, intra, or post-operative period of the surgery. Following surgery, patients reported a significant improvement in all five dimensions of the SAQ (figure).

Conclusions:
In carefully selected patients with severe angina secondary to a hemodynamically significant MB who have failed medical management, surgical unroofing appears to be a safe and effective option for improving physical limitations, anginal symptoms, and overall quality of life.
Abstract 16683: Pretreatment With Clopidogrel In ST-segment Elevation Myocardial Infarction. Evidence From a Meta-analysis
Authors: Nairooz Ramez , Rochlani Yogita , Pothineni Naga Venkata , Sardar Partha , Shavelle David
Published: March 2022

Background:
Current ACC/AHA guidelines recommend a P2Y12 inhibitor in addition to aspirin in ST-segment elevation myocardial infarction (STEMI) patients either on presentation or in the cardiac catheterization laboratory (CCL). In contrast, European guidelines recommend P2Y12 inhibitor administration as soon as possible, but acknowledge that there is no enough evidence to support this class I recommendation.

Aim:
Perform a meta-analysis to examine the hypothesis that pretreatment with clopidogrel in STEMI patients is superior to no pretreatment and CCL administration.

Methods:
We performed a literature search for full length articles comparing clopidogrel administration on presentation (pretreatment) compared with CCL administration in STEMI patients undergoing percutaneous coronary intervention (PCI). We used odds ratio (OR) and random effects model for comparisons. We report mortality, major adverse cardiovascular events (MACE), major bleeding and reinfarction at 30 days.

Results:
A total of 8 studies with 32,509 STEMI patients were included in the analysis. 30 day mortality was significantly lower with pretreatment compared to CCL administration, 4% vs 5% (OR 0.62, 95% confidence interval (CI) [0.46, 0.83]; P=0.002). MACE was significantly lower with pretreatment compared to CCL administration, 6.8% vs 6.3% (OR 0.69, 95% CI [0.58, 0.83]; P<0.0001). Major bleeding was also lower in the pretreatment group (OR 0.80, 95% CI [0.65, 0.97]; P=0.03) that was driven by one study which used more glycoprotein IIb/IIIa inhibitors and more 600 mg loading dose of clopidogrel in the no pretreatment arm. There was no significant difference in reinfarction rates between the groups, 2.6% vs 3.1%.

Conclusion:
Clopidogrel administration at presentation for STEMI patients undergoing PCI decreases 30 day major adverse cardiovascular events and improves mortality.
Abstract 16723: Variation in Atrial Fibrillation Incidence After Atrial Flutter Ablation According to Follow-up Characteristics: Meta-analysis Study
Authors: Pino Maria Isabel , Llanos Oscar L , Hakeem Abdul , Ayoub Karam , Abualsuod Amjad , Nairooz Ramez , Pothineni Naga V , Maskoun Waddah
Published: March 2022

Background:
Atrial Flutter (AFL) is usually initiated with short bursts of Atrial Fibrillation (AF). New-onset atrial fibrillation (AF) after catheter ablation for typical atrial flutter (AFL) has been described in prior studies with significant variation in AF incidence rate. We hypothesized that the variation in the incidence rate depends on the characteristics of the post-ablation follow-up: type and duration of follow up.

Methods:
We performed a meta-analysis by searching online databases for articles from January 1996 to April 2015, and abstracts in the last 2 years which described patients with new AF after successful typical AFL ablation (Complete bidirectional block). We evaluated AF incidence rate based on duration of follow-up in patients who were followed by ECG, clinic visit and Holter monitoring for < 7 days per year. We also evaluated AF rates in studies with < 2 years follow-up based on type of follow-up by categorizing them in 3 groups: Group 1 included ECG, clinical follow-up and symptom-driven evaluation, Group 2 additionally included scheduled 24-hour Holter monitoring for < 7 days per year regardless of symptoms, group 3 included scheduled > 7 days Holter monitoring per year or patients with implant loop recorder.

Results:
A total of 49 studies were included (5452 patients, typical AFL ablation success rate: 95% and no prior AF). Total incidence of new-onset AF was 29% for a weighted mean follow-up of 30 months. Incidence of AF correlated with duration of follow-up as illustrated in the bubble regression plot (figure 1). The incidence of AF was 12.4% in group 1 (755 patients), 19.3% in group 2 (357 patients), 45% in group 3 (178 patients). Mean follow-up duration was 15.2, 18, and 16.4 months respectively.

Conclusions:
The incidence rate of AF after AFL ablation in patients with no prior history of AF, significantly increases with time. Closer monitoring detects a higher rate of AF during short duration follow-up.
Abstract 16739: A Simplified Dichotomous Phenotypic Classification of Bicuspid Aortic Valve Using the Orientation of Coronary Arteries Shows Better Association With Type of Valvulopathy and Combined Aortopathy
Authors: Sun Byung Joo , Lee Sahmin , Jang Jeong Yoon , Choi Hanul , Jin Xin , Lee Ji Hye , Kang Se Hun , Kim Dae-Hee , Song Jong-Min , Kang Duk-Hyun , Song Jae-Kwan
Published: March 2022

Background:
Recently introduced dichotomous phenotypic classification of bicuspid aortic valve (BAV) showed potential association between BAV phenotype and patterns of valvulopathy or aortopathy. However its potential advantage needs to be compared with the conventional BAV classification in a large patient population.

Methods:
In 486 consecutive patients (309 male, 58±14 years) who underwent aortic valve (AV) surgery (n=483) or aortic surgery (n=146), BAV phenotype was classified using echocardiography. Dichotomous classification was based on the orientation of coronary arteries: AP (both coronary arteries originating from the anterior cusp) and RL (each coronary artery originating from each cusp). Conventional classification (type 1 - 4) was based on the fused cusp (Figure). We analyzed the associations between the BAV phenotype and 1) indication of AV surgery (aortic stenosis [AS] vs. regurgitation [AR]), and 2) implementation of aortic surgery.

Results:
BAV-AP (n=271, 56%) was more common than BAV-RL (n=215, 44%). Using conventional classification, fused cusps were indistinguishable in 15% (type 4). Indications of AV surgery included dominant AS (n=352), AR (n=96), and infective endocarditis (IE; n=35). Aortic surgeries were performed for aortic aneurysm (n=135), IE with abscess (n=9), dissection (n=1), and coarctation (n=1). Patients with BAV-RL type presented lower frequency of male (55% vs. 70%, P=0.001), AV surgery for dominant AS (82% vs. 66%, P<0.001), and more frequent aortic surgery (36% vs. 25%, P=0.007) compared to those with BAV-AP. In multivariate analyses, the BAV-RL in dichotomous classification showed more clear association with 1) surgery for dominant AS and 2) aortic surgery compared to the corresponding groups in conventional classification (Figure).

Conclusions:
New classification can overcome the ambiguity of the conventional classification and shows better association with type of valvulopathy and combined aortopathy.
Abstract 16781: Dyssynchronous Ca Removal in Atrial Cardiac Myocytes From Failing Hearts
Authors: Hohendanner Felix , Heinzel Frank R , Blatter Lothar A
Published: March 2022

In heart failure atrial remodeling (AR) leads to impaired contractility and relaxation as well as, atrial fibrillation and contributes to negative clinical outcomes. In myocytes cytosolic Ca removal after systolic release is primarily achieved by SERCA pump and Na/Ca exchange (NCX) activity, allowing atrial relaxation. In atrial myocytes that lack a transverse tubule system, NCX is located exclusively in the cell periphery where it is exposed to high concentrations of Ca during the cardiac cycle. Previously we found that the relative contribution of NCX to Ca removal was increased in AR and was associated with a higher propensity of arrhythmogenic Ca waves, i.e. Ca waves that triggered action potentials (APs). We hypothesize that dyssynchrony of Ca removal globally (whole cell) and locally (peripheral subsarcolemmal (SS) and central (CT) domains) is responsible for impaired relaxation and increased arrhythmogenicity. We used confocal line scan imaging and Ca sensitive dyes (Fluo-4/AM) to investigate Ca removal in remodeled atrial myocytes from a rabbit left ventricular volume-pressure overload systolic heart failure model. In control atrial myocytes Ca removal (assessed by the time constant of decay (TAU) of local SS and CT AP-induced Ca transients) is faster in the cell center (CT region) compared to the SS domain (342±32 vs. 393±31 ms, n=10 cells). In AR myocytes however, CT TAU was not different from SS TAU (196±11 vs. 190+14 ms, n=10 cells). In addition, in AR cells local dyssynchrony (defined as the standard deviation of TAU divided by mean TAU) in the CT domain was significantly increased compared to control (0.11±0.03 vs. 0.04±0.01, n=10 AR and CTRL cells). However despite the increased dyssynchrony, CT Ca removal was 50% and SS Ca removal 56% faster in AR myocytes as compared to control cells (n=10 AR and CTRL cells). In summary, AR myocytes show accelerated but dyssynchronous diastolic Ca removal that may result in impaired relaxation and increased susceptibility to rhythm disorders.
Abstract 16784: Incidence of Cerebral Infarction is Relatively Low in Japanses Patients With Severe Carotid Sclerosis
Authors: Tomaru Takanobu , Matsubara Takumi , Matsubara Erika
Published: March 2022

There have been few reports on prognosis of severe carotid sclerosis(SCS) in association with other cardiovascular disease(CVD).Then we evaluated new development or recurrence of cerebral infarction(CI) (Methods) Severe carotid sclerosis was diagnosed by carotid ultrasonography, and plaque score(PS) was calculated by summation of max thickness of each plaque. The 468 patients with severe carotid sclerosis(SCS: PS >10)were studied and compared those with 262 patients with mild carotid sclerosis(MCS: PS 5). Patients with significant carotid stenosis (’50% in diameter)were excluded. We evaluated hypertension, diabetes mellitus, dyslipidemia and smoking history as risk factors for arteriosclerosis. (Results) In patients with SCS, mean age was 74.7±9.2(mean±SD), and mean PS was13.8. Cerebral infarction(CI) was observed in 114 patients(24.3%). Cardiovascular disease including peripheral artery disease was observed in 158(33.8 %), and coronary artery disease(CAD) only was observed in 124 (26.4 %). In patients with MCS, mean age was 69.5±8.6, and mean PS was 3.82. CI was observed in 28 patients(10.69%)(P 0.0001 vs SCS)Cardiovascular disease was observed in 26 patients(9.92%),and coronary artery disease(CAD) only was observed in 20(7.63%)(P 0001 vs SCS) . In 3 year follow up, CI developed in 13 (2.78%) out of 468 with SCS, and in 4(1.53%) out of 262 patients with MCS. Antiplatelet therapy had been done in 48% of patients with SCS and in 12% of MCS. There was no difference in percentage of antiplatelet therapy between patients with new CI and those without. All patients who developed CI had other cardiovascular disease. Mean number of RF was 2.7±1.0 in patients who developed CI and 2.5±0.9 in those who did not. Conclusions. Incidence of CAD or CI was greater in patients with SCS than in those with MCS. At 3 year follow up of patients with CS, CI did develop more commonly in patients with SCS than in those with MCS, but the difference was not significant. When patient has not severe carotid stenosis, risk of new development or recurrence of CI is very low in Japanese patients with SCS. Presence of poly vascular lesions may be major risk for CI.
Abstract 16815: Long Term Follow up of the Two Incision Technique for Implantation of the Subcutaneous Implantable Cardioverter Defibrillator
Authors: Knops Reinoud , Brouwer Tom
Published: March 2022

Introduction:
The fully Subcutaneous Implantable Cardioverter Defibrillator (SICD) has been introduced as a less invasive option for the prevention of Sudden Cardiac Death (SCD). According to the labeling, the implantation of the device requires three incisions: one pocket incision for the pulse generator and two parasternal incisions to tunnel the lead. These parasternal incisions are a potential source of discomfort and infection. Also the superior parasternal incision leaves a cosmetically notable scar on the upper chest. A less invasive, two incision, implantation technique has recently been introduced that omits the superior parasternal incision. Short term follow-up in a small patient cohort has shown that it is a safe and efficacious alternative for S-ICD implantation and may help to reduce complications. No long term follow up data is available on this technique.

Hypothesis:
Long term follow up in a large patient cohort continues to show the safety and effectiveness of the two incision technique for S-ICD implantation.

Methods:
The two incision technique has been described previously. It makes use of a peelable sheeth to avoid the superior parasternal incision. We performed a retrospective analysis of all the patients in our center that have been implanted with this technique.

Results:
A total of 107 S-ICD patients were implanted with the two incision technique (56% male, mean age 40±16, BMI 25 (16.6-37.3). During a total follow up of 180 years patient years (mean 12 months, range 1-48) no dislocations were observed. One S-ICD system was repositioned due to DFT failure. First shock efficacy during DFT was 96% and 75% (6/8) for spontaneous episodes (100% efficacy with multiple shocks). The 1 year inappropriate shock rate was 7.4%. Device function was normal in all patients, and no inappropriate sensing occurred related to the implantation technique. Four infections occurred of which one originated from the parasternal incision.

Conclusions:
Long term follow up in a large patient cohort continues to show the safety and effectiveness of the two incision technique for S-ICD implantation. This technique offers physicians a less invasive and simplified implantation procedure for the S-ICD.
Abstract 16828: Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-based Studies From 90 Countries
Authors: Mills Katherine T , Bundy Joshua D , Kelly Tanika N , Reed Jennifer , Kearney Patricia M , Reynolds Kristi , Chen Jing , He Jiang
Published: March 2022

Introduction:
Hypertension is the leading preventable cause of premature death worldwide. We aimed to examine the global disparities of hypertension prevalence, awareness, treatment, and control in 2010 and compare secular changes in these disparities from 2000 to 2010.

Methods:
We searched MEDLINE from January 1995 to December 2014 and supplemented with manual searches of references from retrieved articles. A total of 135 population-based studies with 968,419 individuals aged ≥20 years from 90 countries were included. Sex-age-specific prevalences of hypertension from each country were applied to population data to calculate the number of hypertensive adults in each region and globally. Proportions of awareness, treatment, and control from each country were applied to hypertensive populations to obtain regional and global estimates.

Results:
An estimated 30.2% (95% confidence interval, 30.1-30.4%) of the world’s adult population in 2010 had hypertension; 28.6% (28.3-28.9%) in high-income countries and 30.3% (30.1-30.5%) in low- and middle-income countries. An estimated 1.35 billion (1.34-1.36 billion) people had hypertension in 2010; 349 million (339-359 million) in high-income and 1.00 billion (0.99-1.01 billion) in low- and middle-income countries. From 2000 to 2010, age-standardized prevalence of hypertension decreased by 2.3% in high-income countries but increased by 6.1% in low- and middle-income countries. During the same period, the proportions of awareness (56.6% vs 68.8%), treatment (42.9% vs 56.1%), and control (16.6% vs. 28.9%) increased substantially in high-income countries, whereas awareness (34.7% vs 35.1%), treatment (23.4% vs 26.4%), and control (7.0% vs 7.8%) increased only slightly in low- and middle-income countries.

Conclusions:
Global disparities in hypertension prevalence, awareness, treatment, and control are large and increasing. Collaborative efforts from national and international stakeholders are urgently needed to combat the emerging hypertension burden in low- and middle-income countries.