bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17574: Drp1-dependent Mitochondrial Autophagy Plays A Protective Role In Response To Pressure Overload Induced Mitochondrial Dysfunction And Heart Failure
Authors: Shirakabe Akihiro , Ikeda Yoshiyuki , Zai Peiyong , Saito Toshiro , Sadoshima Junichi
Published: March 2022

Dynamin-related protein 1 (Drp1) plays an essential role in maintaining mitochondrial (Mt) quality control through Mt fission and mitophagy. We investigated how Mt function, mitophagy and Drp1 are regulated in the heart during pressure overload (PO) and their roles in regulating cardiac function. Mice were subjected to transverse aortic constriction (TAC) for 1, 3, 5, 7, 14 and 30 days. Left ventricular (LV) weight/tibial length (LVW/TL) was significantly elevated at Day 5 (TAC vs sham; 6.21 ± 0.10 vs 4.59 ± 0.10, p<0.05). Ejection fraction (EF) was maintained at Day 7 (82.1±3.4 vs 78.4±3.2%), but gradually decreased thereafter (at Day 30, 51.0±4.5, p<0.05). Both Mt ATP content (-65.0%, p<0.05) and production (-32.0%, p<0.05) were reduced significantly at Day 7 and thereafter. Mt mass, evaluated by electron microscopy (EM), was reduced (-30.0%, p<0.05) transiently at Day 5. Drp1 was phosphorylated at S616 and accumulated in mitochondria, peaking at Day 3. In EM analyses, autophagosomes containing mitochondria were observed at Day 5 and 7, but not at other time points. Mt DNA content was also transiently decreased below control levels at Day 3 and 5. The levels of COX I and COX IV, Mt matrix proteins, were decreased significantly at Day 3, 5 and 7 compared to sham. These results suggest that PO induces Drp1 translocation and Mt autophagy only transiently around Day 3-7, and that mitochondrial dysfunction develops thereafter. PO-induced decreases in EF (58.2± 6.2 vs 82.2 ± 1.0%, p<0.05), and increases in LVW/TL (6.43 ± 0.82 vs 5.16 ± 0.47, p<0.05) and lung weight/TL (13.31 ± 0.63 vs 7.01 ± 0.66, p<0.05) were all exacerbated in cardiac-specific heterozygous Drp1 knock out (Drp-hetCKO) mice compared to in control mice. Mt mass was significantly greater (1.21 ± 0.46 vs 1.00 ± 0.02, p<0.05) and Mt ATP production was significantly lower (0.58 ± 0.05 vs 1.00 ± 0.02, p<0.05) in Drp-hetCKO than in control mice, indicating accumulation of dysfunctional mitochondria in Drp-hetCKO mice. Although PO transiently induces Mt translocation of Drp1 and Mt autophagy, Mt dysfunction eventually develops, followed by development of heart failure. Endogenous Drp1 protects the heart from failure during PO by inducing degradation of damaged mitochondria.
Abstract 17586: HSP27 Mediated Atheroprotection Requires GM-CSF Induction: Potential Role in Reverse Cholesterol Transport?
(Best of Basic Science Abstract)
Authors: Pulakazhi Venu Vivek Krishna , Adijiang Ayinuer , Shi Chunhua , Chen Yong-Xiang , O’Brien Edward R
Published: March 2022

Introduction:
Previously, we demonstrated that Heat Shock Protein 27 (HSP27) reduces experimental atherogenesis and patients with elevated serum HSP27 levels are relatively protected against future CV events. We previously reported that extracellular HSP27 activates the NF-kB pathway and increases the expression of GM-CSF. While the potential atheroprotective role of GM-CSF remains controversial, clinical reports highlight its effect on reducing serum cholesterol levels. We now hypothesize that GM-CSF plays an important role in HSP27-mediated atheroprotection, potentially by up-regulating reverse cholesterol transport (RCT).

Methods / Results:
1. NF-KB signaling in vitro: Treatment of macrophages with recombinant HSP27 (rHSP27) activated NF-kB 15-fold via TLR-4 (NF-kB reporter gene assay; controls: truncated rHSP27 peptide and TLR-4 deficient cells; p<0.05). While rHSP27 substantially induced GM-CSF expression and secretion (300- and 400-fold respectively; p<0.05) both processes were blocked by NF-kB inhibitors.

2. In vivo role of GM-CSF induction in HSP27-mediated atheroprotection: Aortic atherogenesis in apoE null treated with rHSP27 was reduced by an expected 40%, while ApoE null / GM-CSF null did not respond to rHSP27 treatment. Moreover, apoE null / GM-CSF null macrophages expressed ~33% lower levels of the reverse cholesterol transporters, ABC-A1 and ABC-G1.

3. rHSP27 & Reverse Cholesterol Transport: THP-1 macrophages pre-treated with oxLDL and incubated with rHSP27 for 24h showed enhanced mRNA and protein expression of ABCA1 and ABCG1 (p<0.01). In a RCT assay, THP-1 macrophages labeled with NBD-cholesterol and treated with rHSP27 for 24h before being incubated with apoA1 or HDL showed increased cholesterol efflux compared to controls (p<0.0001 for both).

Conclusion:
HSP27 up regulates expression of GM-CSF that appears to play an important role in RCT-mediated atheroprotection.
Abstract 17604: Identification of Genotype-specific Electrocardiogram Patterns in Long QT Syndrome Using a Novel, Automated T Wave Analysis Program
Authors: Sugrue Alan , Bos J. Martijn , Kremen Vaclav , Qiang Bo , Friedman Paul A , Ackerman Michael J , Noseworthy Peter A
Published: March 2022

Introduction:
Congenital long QT syndrome (LQTS) is a sudden cardiac death-predisposing genetic disorder that has a characteristic electrocardiographic signature. Specific LQTS genotypes have been associated classically with different qualitative electrocardiographic ST - T wave patterns; however, clinical recognition of these patterns could be improved by an automated and quantitative method. We therefore aimed to use a novel, quantitative T wave morphological analysis technique from 12-lead surface ECGs to identify genotype specific LQTS ECG patterns.

Methods:
We analyzed a genotyped cohort of 420 patients (22 ± 15.7years, 43% male) with either LQT1 (61%) or LQT2 (39%). ECG analysis was conducted using a custom T wave program to automatically detect subtle changes in T wave morphology across all 12 Leads. Classification was performed using the top three T wave features in a linear discriminant classifier by 10x10 cross-validation.

Results:
The top three discriminant features were (1) a steeper T wave left slope for LQT1 in lead II (2950 vs 1700 mV/ms, p < 0.0001), (2) a greater center of gravity in 1st segment of T wave in lead aVR in LQT1 (0.248 vs 0.209, p<0.0001) and (3) a smaller Tpeak - Tend/QT ratio in lead aVR in LQT1 (0.20 vs 0.24, p<0.0001). Using these top three features, we were able to successfully differentiate LQT1 and LQT2 in 79% of cases (figure 1).

Conclusions:
An automated morphological T wave analysis was able to discriminate between the two most common LQTS genotypes. This novel method enhances phenotypic characterization of LQT and could have a significant clinical impact on the diagnosis and management of patients with suspected LQTS.
Abstract 17681: Stress Cardiomyopathy Developed in Patients With Cancer: Clinical Characteristics and Outcomes
Authors: Jeong Yeong jin , Kim Ju Hyeon , Park Jinoh , Lee Cheol Hyun , Cho Min Soo , Bae Jae Seok , Kim Yu Na , Lee Pil Hyung , Jang Jeong Yoon , Lee Sahmin , Kim Dae-Hee , Song Jong-Min , Choi Kee-Joon , Kang Duk-Hyun , Song Jae-Kwan
Published: March 2022

Introduction:
Sporadic case reports have shown that stress cardiomyopathy (SCM) can happen during treatment of underlying malignancy. However, clinical association between cancer and SCM needs further investigation.

Methods:
Echocardiographic data base from Jan 2009 to June 2014 was used to identify SCM patients in whom clinical and imaging data information was used to rule out classic myocardial infarction. Clinical characteristics, underlying comorbidities, and outcomes including in-hospital mortality were explored.

Results:
We retrospectively identified 549 consecutive patients (age, 64±15 years; 328 female) with SCMP in a single tertiary referral hospital. Among them, 210 patients had an active history of cancer (group 1, 38%), whereas the resting 339 did not (group 2). Hematologic malignancy including leukemia, lymphoma and multiple myeloma was the most common (n=44, 21.0%), followed by lung (n=39, 18.6%), stomach (7.6%), ovary (6.2%), and colorectal cancer (5.7%). Group 1 was characterized by younger age (62±13 vs. 65±16 years, p=0.002) with lower frequency of coronary risk factors, lower prevalence of female gender (54±63%, p=0.04), and lower frequency of underlying comorbidities including renal failure, stroke and heart failure. Physical illness associated with underlying medical conditions such as sepsis was the most common triggering event (79%), followed by routine surgery or procedure (18%); SCM triggered by emotional stress is very rare (<5%). Typical apical ballooning was present in 70% with atypical apical-sparing ballooning in 30% and this pattern did not show any difference between two groups. Left ventricular ejection fraction was lower in group 1 with higher prevalence of right ventricular ballooning, pulmonary hypertension and pericardial effusion. Hospital mortality was higher in group 1 (29% vs 20%, p=0.017) and active history of cancer was an independent factor associated with hospital mortality (odds ratio 1.60, 95% CI 1.063 - 2.410, p = 0.024). SCM development was not associated with history and timing of chemotherapy, which did not affect hospital mortality either.

Conclusions:
Cancer is an important risk factor of SCM development in a tertiary referral hospital and should be considered a poor prognostic factor.
Abstract 17686: The Association Between Physical Activity Intensity and Left Atrial Size Among Healthy Adults: The Cooper Center Longitudinal Study
Authors: Darden Douglas J , Pandey Ambarish , Ayers Colby , Radford Nina , DeFina Laura , Willis Benjamin , Barlow Carolyn , Berry Jarett D
Published: March 2022

Introduction:
Increased left atrial (LA) volume has been proposed as a mechanism through which high levels of physical activity (PA) might increase the risk for atrial fibrillation (AF). However, the relationship between the intensity of PA and LA volume has not been previously reported. We hypothesized that vigorous activity would be more strongly associated with LA volume when compared to moderate PA.

Methods:
We included 1,641 healthy participants (age 55.6 years, 53.4% men) from the echocardiography substudy of the Cooper Center Longitudinal Study who were free of cardiovascular disease. PA was measured by self-report questionnaire that quantified the amount of moderate and vigorous PA performed in mins per week. LA volume was measured by 2D echocardiography using the biplane area-length method. The association between PA and LA volume indexed to body surface area was estimated using multivariable linear regression models with LA volume as the dependent variable and total, moderate, and vigorous activity (in min/per week) as the independent variables. Models were additionally adjusted for age, body mass index (BMI), hypertension, diabetes, and fitness.

Results:
Average levels of moderate, vigorous, and total PA in the study sample were 111, 103 and 191 min/week, respectively, with 68% of participants reporting some level of PA. As expected, higher levels of PA were associated with a lower BMI, lower blood pressure, and lower diabetes prevalence (p<.05 for all). In multivariable adjusted models, age, fitness, BMI and higher vigorous activity were associated with a larger LA size. However, there was no apparent association between moderate PA and LA size (see table).

Conclusion:
Higher vigorous but not moderate PA was associated with a larger LA size. These data suggest that lower intensity exercise prescriptions might be preferred in clinical circumstances marked by concern for AF risk.
Abstract 17819: Implications of the Post-myocardial Infarction Bimodal Edematous Reaction for Quantifying Area at Risk, Infarct Size And Salvaged Myocardium by Cardiac Magnetic Resonance Imaging
Authors: Fernández-Jiménez Rodrigo , Galán-Arriola Carlos , Agüero Jaume , Sánchez-González Javier , García-Prieto Jaime , López-Martin Gonzalo J , García-Lunar Inés , Pizarro Gonzalo , Fuster Valentin , Ibanez Borja
Published: March 2022

Background:
Contrary to the accepted view, it has been recently demonstrated that myocardial edema after ischemia/reperfusion (I/R) follows a bimodal pattern during the first week.

Purpose:
To study the implications of the bimodal edema phenomenon on the cardiac magnetic resonance (CMR)-measured area at risk (AAR), infarct size and salvaged myocardium.

Methods:
Closed-chest 40min I/R was performed in 20 pigs. True anatomical AAR was assessed by arterial enhanced multidetector computed tomography (CT) performed during coronary occlusion. CMR with CINE, T2-weighted short-tau inversion recovery and late gadolinium-enhanced (LGE) sequences were performed at every follow-up (120 min, 24 hours, day 4 and day 7 after reperfusion) for the quantification of left ventricular mass, edema (CMR-AAR), and necrosis (infarct size). Salvaged myocardium was calculated by correcting infarct size for CMR-AAR extent.

Results:
A sharp increase in left ventricular mass due to huge swelling of the ischemic tissue was detected in early reperfusion (Figure 1A and 1E) leading to overestimation of CMR-AAR as compared to true AAR by CT at this time-point (Figure 1B and 1E). Due to reabsorption of initial edema and presence of significant hemorrhage, CMR-AAR was barely detectable at 24 hours while due to the progression of the deferred wave of edema, CMR-AAR accurately delineated true AAR at day 4 and day 7 (Figure 1B and 1E). A progressive decrease in infarct size was shown in LGE sequences (Figure 1C and 1E). As a consequence, salvaged myocardium dynamically varied within the first week after I/R (Figure 1D).

Conclusions:
The bimodal edematous reaction after I/R greatly impacts on the non-invasive quantification of CMR-AAR, infarct size and salvaged myocardium by CMR. The most appropriate day to perform CMR after reperfused infarction seems to be around day 7 coinciding with the peak of the deferred wave of edema.
Abstract 17867: The Pro-angiogenic Long Non-coding Rna Tykril Controls Human Pericyte Function Through Regulation Of P53 Activity and Pdgfrß Expression
Authors: Zehendner Christoph M , Werner Astrid , Bischoff Florian , Boeckel Jes-Niels , Demolli Shemsi , Michalik Katharina , Meder Benjamin , Katus Hugo A , Haas Jan , Chen Wei , John David , Uchida Shizuka , Zeiher Andreas M , Dimmeler Stefanie
Published: March 2022

Rationale:
Pericytes contribute to the formation, maturation and stabilization of blood vessels, making them indispensable for proper cardiovascular organ function. Although long non-coding RNAs (lncRNAs) are pivotal in cardiovascular development, their role in pericytes has so far been neglected.

Objective:
Here we assessed the hypothesis that lncRNAs significantly regulate pericyte function.

Methods and Results:
Via RNA deep sequencing we show that the hypoxia induced lncRNA TYKRIL (Tyrosine Kinase Receptor Inducing lncRNA) modulates expression of the tumor suppressor p53 and Platelet derived growth factor receptor beta (PDGFRß) in human pericytes. Luciferase reporter arrays demonstrated that silencing of TYKRIL with GapmeRs (0.22+0.04 vs. scramble Ctrl., n=8, P<0.001) significantly enhances activity of p53 (2.9+0.55 fold induction vs. scramble Ctrl., n=3, P=0.0103). TYKRIL knockdown increased acetylation of the p53 lysine residue K382, which is known to be required for p53 activation. TYKRIL silencing downregulated the known p53 target PDGFRß (protein expression: 0.46+0.08 vs. Ctrl., n=4, P<0.001) which consecutively disrupted AKT and ERK1/2 phosphorylation. Thereby, pericyte viability (MTT cell viability: 0.8+0.03 vs. Ctrl., n=3, P<0.01), proliferation (Ki67 proliferation index fold change 0.71+0.05 vs. Ctrl., n=6, P<0.001) and recruitment towards endothelial cells in matrigel co-culture assays was markedly reduced (fold change 0.37+0.03 vs. Ctrl., n=5-7, P<0.001). In turn, silencing of p53 reversed these effects (MTT cell viability: TYKRIL knockdown + scramble 0.7+0.04; TYKRIL knockdown + siRNAp53 0.94+0.04, n=11-12, P<0.01).

In patients with ischemic heart failure (n=18), cardiac TYKRIL and PDGFRß expression are significantly reduced compared to controls (TYKRIL vs. Ctrl. 0.01+0.005, P<0.001; PDGFRß mRNA expression: 0.44+0.11, P<0.05).

Conclusion:
Our results identify TYKRIL as a pro-angiogenic lncRNA that is down-regulated by ischemic heart failure and significantly regulates pericyte viability and recruitment towards endothelial cells by repression of p53 activity and stabilization of PDGFRß signalling.
Abstract 17900: Medical Therapy Influences Outcome Of PCI Vs CABG Comparison Studies
Authors: Kurlansky Paul , Herbert Morley , Prince Syma , Mack Michael
Published: March 2022

Introduction:
Multiple studies have compared coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) to determine the optimal strategy for coronary revascularization (CR). Very few have evaluated the impact of medication history on the relative outcomes.

Hypothesis:
Evidence-based medical therapy influences outcomes of CABG vs. PCI

Methods:
All non-STEMI patients (N=3871 PCI, 1181 CABG) undergoing isolated CR in eight community-based hospitals were enrolled. Follow-up (63.5±27.9, median 79.7 months) was obtained at 12, 18 and >60 months by patient/physician contact and Social Security Death Index. Kaplan-Meier curves were used to compare survival free of MACE (nonfatal myocardial infarction, PCI, CABG, mortality) between groups,.

Results:
Compliance with appropriate anti-platelet therapy improved long-term freedom from MACE in both PCI and CABG patients (Figure 1). Similarly, lipid-lowering therapy improved MACE-free survival in both PCI and CABG patients (Figure 2). Interestingly, treatment with beta blockers appeared to have either a negative (PCI) or marginal (CABG) impact.(Figure 3), most likely representing patient selection.

Conclusion:
Medication history has a dramatic impact on the long-term outcomes of both PCI and CABG patients and therefore must be included in the evaluation of comparative strategies for revascularization.
Abstract 17947: Regulator of G-Protein Signaling 5 Prevents Smooth Muscle Cell Proliferation and Attenuates Neointima Formation
Authors: Daniel Jan-Marcuss , Prock Andre , Dutzmann Jochen , Bauersachs Johann , Sedding Daniel
Published: March 2022

Introduction:
Regulator of G-protein signaling 5 (RGS5) is abundantly and specifically expressed in vascular smooth muscle cells (SMCs) and inhibits G-protein signaling by enhancing the GTP-hydrolyzing activity of Gα-subunits.

Hypothesis:
In the present study, we aimed to investigate the effects of RGS5 on vascular SMC function in vitro and neointima formation in vivo and to determine the underlying molecular mechanisms.

Methods:
Expression of RGS5 was assessed in vitro and in vivo by qPCR, immunoblotting and immunohistochemistry. Proliferation and migration of human coronary artery SMC were assessed in vitro following the adenoviral-mediated over expression of wild type (WT) RGS5, of a non-degradable mutant (C2A-RGS5) or siRNA-mediated knock down. In vivo, the proliferation and neointima formation were assessed in a wire-mediated injury model of the femoral artery in C57BL/6J mice.

Results:
We found a robust expression of RGS5 in native arteries of C57BL/6 mice and a significant down-regulation within neointimal lesions 10 and 21 days after vascular injury as assessed by qPCR, immunohistochemistry and immunoblotting. In vitro, RGS5 was found significantly down-regulated after mitogenic stimulation of SMCs. Overexpression of RGS5 or, even more prominently, the C2A-RGS5 mutant prevented SMC proliferation and migration. In contrast, the siRNA-mediated knockdown of RGS5 significantly augmented SMC proliferation. Following overexpression of RGS5, FACS analysis of propidium iodide-stained cells indicated cell cycle arrest in G0/G1 phase. Mechanistically, inhibition of ERK1/2 phosphorylation and MAPK downstream signaling was found to be responsible for the anti-proliferative effect since over expression of a constitutive active form of MEK reversed the growth-inhibitory effect of of RGS5. Following wire-induced injury, adenoviral-mediated overexpression of RGS5 or C2A-RGS5 significantly decreased ERK phosphorylation, SMC proliferation and neointima formation in vivo (n=8; p<0.001).

Conclusions:
Down-regulation of RGS5 is an important prerequisite for SMC proliferation and neointima Formation. Therefore, reconstitution of RGS5 levels might represent a promising therapeutic option to prevent vascular remodeling processes.
Abstract 17970: Atrial Fibrillation is Associated With Increased Atrial Metabolic Activity on FDG/PET Imaging in Patients With Ischemic Cardiomyopathy
Authors: Santi Nicolas D , Beanlands Rob , McArdle Brian , deKemp Robert , Nery Pablo , Renaud Jennifer , Chow Benjamin , Hessian Renee , Davies Ross , Ruddy Terrence , Guo Ann , Hadizad Tayebeh , Birnie David
Published: March 2022

Introduction:
Atrial Fibrillation (AF) is a common arrhythmia but its pathogenesis remains incompletely understood. Alterations in metabolism may play a role. 18F-fluorodeoxyglucose (FDG) PET reflects glucose uptake in metabolically active tissue but studies evaluating the relationship between atrial FDG uptake and atrial fibrillation are limited.

Hypothesis:
We hypothesized that patients with ischemic cardiomyopathy who have had AF have increased atrial wall FDG uptake compared to patients without AF (no-AF).

Methods:
Atrial uptake was assessed visually and quantitatively on FDG-PET/CT images in 42 patients (24 AF, 18 no-AF). The maximum and mean FDG Standard Uptake Value (SUV) in the left atrium (LA), right atrium (RA) and mean blood pool activity were measured (see figure). The Tissue:Blood ratio (TBR) was calculated using the maximum atrial wall SUV (TBRmax) and mean SUV (TBRmean).

Results:
Median age was 72 years; (78% male). Mean LVEF was similar between AF vs. No-AF patients (24+/-10% vs. 26+/-11%, p=0.57). The RA was visualized in 88% of AF and 44% of no-AF patients (p=0.002). The LA was visualized in 88% of AF and 72% of no-AF patients (p=0.22). See table for TBR results. TBRmax and TBRmean were significantly increased in the RA wall of patients with AF vs. no-AF. There was a trend for increased FDG in the LA wall of AF patients.

Conclusion:
Among patients with ischemic cardiomyopathy, significantly greater FDG uptake was noted in the RA of patients with AF vs. No-AF (with a trend for LA uptake). These findings suggest increased glucose metabolism in the atria in patients with AF. Further study is warranted to determine the clinical and biological significance of these findings.
Abstract 18022: Improved Assessment of CAD in Women With Flurpiridaz F-18 PET Myocardial Perfusion Imaging: Results of Subset Analysis of the Flurpiridaz F-18 Phase 3 Study
Authors: Heller Gary V , Maddahi Jamshid , Udelson James E , Beanlands Robert , Knuuti Juhani , Bateman Timothy M , Berman Daniel S , Lazewatsky Joel , Orlandi Cesare
Published: March 2022

Background:
Coronary artery disease (CAD) is under-diagnosed in women. Flurpiridaz F 18 injection (flurpiridaz) is a PET myocardial perfusion imaging (MPI) tracer in clinical development. We hypothesized flurpiridaz would result in improved CAD detection in women in comparison to SPECT.

Methods:
This Phase 3 study was designed to assess the diagnostic efficacy of flurpiridaz and SPECT with Tc99m-labeled agents for CAD detection in the same patients. Patients with known or suspected CAD who were either scheduled for or had completed invasive coronary angiography (without intervention) were included. Each patient was studied using both rest/stress flurpiridaz PET MPI and rest/stress Tc-99m labeled SPECT MPI. Images were interpreted by 3 expert readers blinded to all clinical information. Quantitative coronary angiography (QCA) was used with patients considered CAD positive with a stenosis ≥50% in at least one major vessel.

Results:
795 subjects were enrolled at 72 clinical sites in US, Canada and Finland. The study included 235 (30%) evaluable female subjects with a mean age of 62.4±10.1 years, body weight of 85.0±21.6 kg, and a BMI of 32.3±7.8 (58.7% with a BMI≥30). The agent was safe and well tolerated. A statistically significant greater sensitivity was seen for flurpiridaz (67.8%) vs SPECT (37.3%, p<0.001). Similar specificity was shown for flurpiridaz (81.3%) vs SPECT (80.1%) (p=0.017 for non-inferiority testing). The diagnostic superiority of flurpiridaz vs SPECT was also demonstrated by ROC analysis (p<0.001). Statistical superiority of flurpiridaz vs SPECT was shown for diagnostic accuracy (p=0.014), image quality (p<0.001), and interpreter certainty (p<0.001), with a significant reduction (~50%) in radiation exposure for flurpiridaz vs SPECT (p<0.001).

Conclusions:
The results of this Phase 3 trial demonstrate the superiority of flurpiridaz over standard SPECT MPI for the assessment of CAD in women, with lower radiation exposure than standard SPECT.
Abstract 18131: Canadian Multi-center Experience With WATCHMAN for Percutaneous Left Atrial Appendage Closure
Authors: Saw Jacqueline , Fahmy Peter , Azzalini Lorenzo , Marquis Jean-Francois , Hibbert Benjamin , Morillo Carlos , Carrizo Aldo , Ibrahim Reda
Published: March 2022

Background:
There is limited data with WATCHMAN for left atrial appendage (LAA) closure in patients with nonvalvular atrial fibrillation (AF) and contraindications to anticoagulation. The purpose of this study was to evaluate the safety and efficacy of WATCHMAN in our early Canadian experience.

Methods:
We report our consecutive series of patients who underwent WATCHMAN implantation at 4 Canadian centers (Vancouver General Hospital, Montreal Heart Institute, Hamilton General Hospital and Ottawa Heart Institute). Indications for LAA closure were CHADS2≥1, and contraindication/intolerance to or failure on anticoagulation. All cases were done under general anesthesia and TEE guidance. Majority of patients received dual antiplatelet therapy (DAPT) for 3-6 months after implant. Follow-up TEE was typically performed at 1-6 months post-procedure.

Results:
Ninety patients underwent LAA closure with WATCHMAN from May 2013 to June 2015. The mean age was 75.0 ± 7.9. The mean CHADS2 score was 2.9 ± 1.2, CHADS-VASc score was 4.4 ± 1.5, and HASBLED score was 3.2 ± 1.2. Permanent AF was present in 66.7% and paroxysmal AF in 33.3%. Indications for LAA closure were prior bleeding in 81 patients (90.0%; 74 major bleeding, and 7 minor bleeding), 9 were deemed high-risk for bleeding (renal failure, cirrhosis, labile INR, esophageal ulcers, on DAPT), and 1 with recurrent strokes on warfarin. Procedural success was 97.8% (88/90), with one device embolization (snared percutaneously) and one implant failure due to inadequate LAA depth. There was no procedural stroke/TIA, death, MI, or cardiac tamponade. There were 3 major bleeding that required transfusions. Mean hospital stay was 1.4 ± 1.8 days. Antithrombotic therapy post-implant included DAPT in 66/90 (73.3%), anticoagulant in 21/90 (5 warfarin, 16 direct anticoagulant), and aspirin alone in 3/90. Follow-up TEE was available in 53 patients, there was 1 device-associated thrombus (treated successfully with anticoagulation), and 18 peri-device leaks (all <5mm). Mean follow-up was 173.8 ± 117.3 days, with no stroke or death, but there was 1 TIA and 3 major bleeding.

Conclusion:
In our early Canadian experience, WATCHMAN for LAA closure in patients contraindicated to anticoagulation is safe and effective.
Abstract 18132: Prenatal Evaluation of the Fetal Cardiovascular Profile Score in a Multicenter Study of Ebstein Anomaly/Tricuspid Valve Dysplasia
Authors: Freire Grace , Freud Lindsay , Tworetzky Wayne , Escobar Maria , Kumarlu Rukmini , Huhta James , Wilhm Marilyn , Amankawh Ernest , Martinez Denise , Vernon Margaret , Michelfelder Erik , Kovalchin john , Ikemba Catherine , Samai Cyrus
Published: March 2022

Introduction:
The cardiovascular profile (CVP) score is an echo based multivariable approach for assessment of fetal hemodynamics. The CVP score has been shown to be useful in predicting the outcome of fetuses with heart failure, growth restriction, and select congenital heart defects. The score ranges from 0 to 10, with points deducted for abnormal hemodynamics. In a previous pilot study of 21 fetuses with EA/TVD, a CVP score <7 was associated with poor outcomes. The aim of this study was to investigate the prognostic significance of the CVP score in a larger cohort of fetuses with EA/TVD.

Methods:
This 23-center study was a retrospective review of fetal echo data and outcomes in a cohort of 243 fetuses diagnosed with EA/TVD from 2005-2011. Both the first and last fetal echo in gestation were evaluated. Hydrops, heart size, cardiac function, and umbilical arterial and venous Dopplers were scored. The primary outcome was perinatal death, defined as fetal demise or death prior to neonatal discharge. Categorical variables were compared using Chi-squared tests; p-values <0.05 were considered statistically significant.

Results:
Complete data on the first and last fetal echocardiograms to calculate a CVP score were available in 144 fetuses at the time of the first fetal echo (median GA 26.07 wks, range 14-40) and 73 fetuses at the time of the last fetal echo (median GA: 25 wks, range 18 -34). The median CVP scores for the first and last fetal echo were 8 (range 4-9) and 7 (range 7-9) among survivors vs. 7 (range 0-10) and 6 (range 1-8) among non-survivors. Fetuses with EA/TVD that died were more likely to have a CVP score <7 compared to those that survived: 33.3% vs. 11.6 %, (p=0.004) on the first fetal echo and 60.0% vs. 28.6 % (p=0.015) on the last fetal echo. However, no statistically significant difference in survival was observed for fetuses whose CVP score decreased from the first to the last echo. (p=0.95).

Conclusions:
In this study, fetuses with EA/TVD with CVP scores <7 on the first or last fetal echo were less likely to survive. The CVP score may be a valuable tool to identify fetuses with EA/TVD at risk of poor outcome for whom novel therapeutic approaches might be warranted.
Abstract 18173: Medical Management of Papillary Fibroelastoma is Associated With Low Risk of Embolization in Selected Cases
Authors: Bauch Terry , Htun WahWah
Published: March 2022

Introduction:
Papillary fibroelastoma (PFE) is a rare primary cardiac tumor with a variable clinical spectrum. Surgical excision is recommended in symptomatic patients, but the optimal management of asymptomatic patients is quite controversial.

Hypothesis and Method:
We hypothesized that non-surgical cases would have excess embolic events, and performed a retrospective and prospective observational study to evaluate the course of patients diagnosed with PFE at our institution. We queried our echo database from 2006 to 2014 for patients age 18 years or older with a mass suggestive of PFE on a cardiac valve by TTE or TEE; significant valvular calcifications, endocarditis, or serial echos with contradictory interpretations were excluded. Electronic health records were reviewed, and those with available outcomes data comprised the final study cohort. Outcomes were collected prospectively from time of identification through May 1st, 2015.

Results:
We identified 60 cohort patients aged 29 to 89 years (mean 67 +-12); 60% were women, and 85% of PFE were on the aortic valve, with the largest reported dimension 0.2 cm to 1.4 cm. Follow-up data were available for 3 to 126 months (median 40). Surgical excision was performed on 22 patients (38%), mean age 66 +-11 years. Among the remaining 38 patients who did not undergo initial excision, mean age 67 +- 12 years, frailty was cited as the justification in 50%. In the initial non-surgical cohort, 12 received coumadin for unrelated indications such as atrial fibrillation, and 22 received daily Aspirin. In the initial non-surgical cohort, 15 underwent surgical valve repair with resection of the PFE and 7 underwent valve replacement. No post-surgical recurrences were found by TTE. None of the patients in the entire cohort had clinically evident embolic events during follow-up.

Conclusion:
This is the first reported study to include prospective outcomes data for PFE. Our data suggest that watchful waiting may be a reasonable strategy in selected patients. The optimal medical therapy remains unknown, and larger randomized trials are needed to establish practice guidelines.
Abstract 18176: Thirty-day and Long-term Outcomes After Transcatheter Aortic Valve Implantation From First-in-man to Sapien 3: 13 Years Rouen Experience
Authors: Durand Eric , Bauer Fabrice , Tron Christophe , Glinel Bastien , Litzler Pierre-Yves , bessou Jean-Paul , Cribier Alain , Eltchaninoff Hélène
Published: March 2022

Introduction:
Since the first-in-man transcatheter aortic valve implantation (TAVI) performed by our group in 2002, the number of procedures has dramatically increased. Currently restricted to inoperable and high-risk patients TAVI is likely to be extended to lower risk patients. However, long-term data regarding valve durability are missing. We aimed to report our experience with long-term follow-up to assess long-term mortality and valve durability.

Methods:
All consecutive patients presenting with severe symptomatic aortic stenosis treated by TAVI were included prospectively. Clinical and echocardiographic follow-up was performed at 30 days and annually thereafter. Survival curves were constructed using Kaplan-Meier analysis. We also evaluated valve durability and the incidence of infective endocarditis.

Results:
Between 2002 and 2015, 784 consecutive patients (age: 83.3±9.4 years, logistic EuroSCORE of 19.6±12.1%) underwent TAVI including 634 (80.9%) patients via a femoral approach. A balloon-expandable transcatheter heart valve (THV) was predominantly used (747 Pts; 95.3%): 68 Cribier-Edwards, 114 Sapien, 482 Sapien XT, and 83 Sapien 3 since July 2014. Thirty-day mortality dramatically decreased from 22.1% using the Cribier-Edwards in compassionate patients to 1.3% with the Sapien 3 (p<0.0001). Survival curves in the overall population and according to the type of valve are presented in the Figure. Mean aortic gradient remained unchanged during follow-up up to nine years, and only one patient presented with stenotic degenerated THV Sapien valve successfully treated by a valve-in-valve procedure. Four (0.5%) patients had infective endocarditis.

Conclusions:
Long-term (up to 9 years) follow-up of our large series of patients treated by TAVI demonstrates no warning signs of valve deterioration suggesting very encouraging valve durability, using predominantly, a balloon expandable prosthesis.
Abstract 18221: Flow Characteristics of CoreValve Transcatheter Aortic Valve: Implications for Calculation of Stroke Volume and Effective Orifice Area
Authors: Hamid Nadira , Khalique Omar , Williams Mathew , George Isaac , Nazif Tamim M , Vahl Torsten , White Jonathan , Parikh Puja , Kodali Susheel , Leon Martin , Hahn Rebecca
Published: March 2022

Background:
The hour-glass shape of the CoreValve THV used for TAVR has raised questions assessing stroke volume (SV) and effective orifice area.

Objective:
To determine the optimal location of diameter for calculating SV for the CoreValve THV.

Methods:
98 TAVR patients with CoreValve THV had intra-procedural TEE analyzed at 3 levels in a mid-systolic frame: the outer-to-outer border of the inflow region (outer level), the inner-to-inner border just within the inflow (inner level), and the inner-to-inner border at the level of neo-aortic leaflets (mid level). Patients with ≥mild paravalvular or pulmonary regurgitation were excluded. THV area was directly planimetered at these levels using 3D TEE. SV was calculated using pulsed Doppler VTIs obtained at these levels, paired with the respective THV area by 2D (SV2D-OUT, SV2D-IN and SV2D-MID) and by 3D (SV3D-OUT, SV3D-IN and SV3D-MID). Right ventricular outflow tract (RVOT) area was calculated from 2D or planimetered directly from CT to calculate SV2D-RVOT and SV3D-RVOT.

Results:
TEE 2D measurements were performed in 53 patients with 3D measurements in a subset of 27 patients. There was a significant difference between SV2D-RVOT and SV3D-RVOT (p = 0.002) (Table 1). There were no significant differences between the SV2D-RVOT and left-sided SV at all 3 levels. There was a significant difference in SV3D-RVOT and SV3D-MID but not SV3D-OUT or SV3D-IN. For 2D SV measurements, a strong correlation to SV2D-RVOT was observed at all levels (r = 0.94-0.97, p < 0.0001)). For 3D measurements, correlation to SV3D-RVOT was significant although modest (r = 0.46-0.63, p > 0.01). For the subgroup with SV3D-RVOT, there were significant differences in SV2D-OUT (53.7±15.1, p = 0.002), SV2D-IN (53.5±15.0, p = 0.001), and SV2D-MID (53.8±14.2, p = 0.002).

Conclusions:
This study suggests that consistent SV can be calculated using 2D THV diameters with matching VTI at multiple locations and there is no significant flow acceleration within this valve.
Abstract 18257: A Novel Portable Polyvinylidene Fluoride Based Sensor for Detection of Hemorrhage
Authors: Ansari Sardar , Slavin Daniel , Tiba Mohamad H , Derksen Harm , Oldham Kenn , Ward Kevin , Najarian Kayvan
Published: March 2022

Introduction:
Hemorrhage (Hem) is one of the leading causes of mortality from trauma, and continuous monitoring for Hem using techniques such as traditional BP, especially in field conditions, poses significant challenges. We have built a portable low-powered noninvasive sensor for continuous vascular tone monitoring to detect significant Hem as an alternative to BP monitoring. The sensor, made of polyvinylidene fluoride (PVDF) material, can sense and record changes in the mechanical properties of arteries due to peripheral vasoconstriction caused by Hem.

Methods:
Nine pigs underwent Hem by femoral artery bleeding. Systolic arterial pressure (SAP) was used to select 16 instances of significant hemorrhage (SAP>85mmHg pre-Hem and >10mmHg drop in SAP post-Hem). The PVDF signal was measured from the animal’s distal forelimb. A piecewise linear estimation of the PVDF signal was computed using a newly developed Taut String algorithm such that the error was <4% of the signal amplitude. The number of pieces in each period was used as a complexity score (CS) to detect Hem.

Results:
Arterial BP and the CS derived from the PVDF signal for one subject (Fig), as well as snapshots from the PVDF signal demonstrating morphology changes are shown. Maximum separation between pre- and post-Hem CS was achieved by a threshold of 5.5; 14 instances (87.5%) transitioned from CS≥6 to 5 within 5 minutes of the onset of HS (t0) while the remaining 2 instances transitioned from CS=5 to 3. The average detection delay was 1.95±1.2 min. These changes corresponded to >10mmHg decrease in SAP from baseline. CS improved during subsequent resuscitations.

Conclusions:
The proposed low-powered portable sensor captures continuous vascular tone and can be used to detect significant Hem in a continuous manner that may offer diagnostic and therapeutic guidance as an alternative to traditional intermittent BP measures. The results indicate that the derived CS can effectively separate the signals pre- and post-Hem.
Abstract 18317: Impact of Pulmonary Valve Replacement on Right Ventricular Myocardial Deformation in Repaired Tetralogy of Fallot
Authors: Yim Deane , Mertens Luc , Friedberg Mark , Grosse-Wortmann Lars , Morgan Conall , Dragulescu Andreea
Published: March 2022

Introduction:
Pulmonary regurgitation is common following tetralogy of Fallot (TOF) repair and leads to progressive right ventricular (RV) dilatation and dysfunction. There is limited data on ventricular remodeling and adaption following surgical pulmonary valve replacement (PVR), especially beyond the short-term.

Hypothesis:
Our objective is to assess medium-term effects of PVR on right ventricular mechanics in patients with surgically repaired TOF.

Methods:
Speckle-tracking echocardiography was performed on pre-operative and post-operative echocardiograms in 50 patients with repaired TOF who underwent surgical PVR. RV global and segmental myocardial deformation parameters were assessed. Transthoracic studies 2.1±2.1 months pre-PVR, 2.23±0.61 months post-PVR (early follow-up) and 14.9±3.8 months post-PVR (medium-term follow-up) were analyzed.

Results:
The mean age at PVR was 12.6±3.3 years. Global RV longitudinal strain fell from -19.2%±2.7% to -16.8%±2.6% at early follow-up (p<0.001) but increased by late follow-up to -21.9%±3.1% (p<0.001). Basal segmental RV longitudinal strain showed a similar early reduction in strain followed by improvements late post-operatively (p<0.001). Mid-segmental RV longitudinal strain improved by late post-operative follow-up (p=0.002), whereas apical segmental RV strain increased in the early post-operative period (p=0.004). There was a weak inverse correlation between pre-operative RV indexed end-diastolic volumes and RV mean longitudinal strain (R2=0.383).

Conclusion:
Although an early reduction in RV longitudinal strain occurs following PVR, the volume unloading effects of PVR has a significant effect on late RV remodelling as reflected by improvements in global RV longitudinal, basal and mid segmental strain late post-PVR. The effects of reversed remodelling of the RV may have important clinical implications towards determining the optimal timing of PVR in this subset of patients.
Abstract 18322: No Short-term Mortality Benefit With Endovascular Therapy in Acute Ischemic Stroke: A Systematic Review and Meta-analysis
Authors: Khan Sobia , Salahuddin Hisham , Cabatingan Kent A , Luni Faraz K , Khan Abdur R , Buehler Mark A , Zaidi Syed F , Jumaa Mouhammad A , Moukarbel George V
Published: March 2022

Background:
The efficacy of endovascular treatment in improving functional outcome in acute ischemic stroke has been established. However, it is unclear if there is any beneficial effect on mortality in stroke patients undergoing prompt endovascular treatment.

Methods:
Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus were searched from inception through June 2015 for randomized controlled trials that compared endovascular treatment to the current standard of care in acute ischemic stroke. Studies were selected if they had short-term (90 day) mortality as a measured outcome. Mortality was pooled and odds ratio (OR) was calculated using the Mantel-Haenszel method using a fixed effect model.

Results:
There were 10 studies with 2835 participants in our analysis. There were 224/1513 (14.8%) deaths reported in the endovascular treatment arm and 214/1322 (16.2%) deaths in the current standard of care arm. There was no difference in 90 day mortality between endovascular treatment and current standard of care (OR 0.86, 95% CI= 0.70-1.06, p =0.51; I2 = 0%). The Figure shows forest plot comparing 90-day mortality in the endovascular treatment arm and the current standard of care arm in patients with acute ischemic stroke. There was visual estimation of publication bias which was not confirmed by trim and fill method.

Conclusions:
In this meta-analysis we did not find any short term mortality benefit with rapid endovascular treatment as compared to current standard of care. With the improvement demonstrated in functional outcomes, endovascular intervention represents a paradigm shift in stroke therapy. However, more studies are needed to look at both short and long-term survival and cost effectiveness of the modality.
Abstract 18330: Direct Transport to a PCI Center Following Out-of-Hospital Cardiac Arrest is Associated With Improved Survival in North Carolina
Authors: Kragholm Kristian , Malta Hansen Carolina , Dupre Matthew , Xian Ying , Strauss Benjamin , Tyson Clark , Monk Lisa , Corbett Claire , B. Fordyce Christopher , A. Pearson David , L. Fosbol Emil , G. Jollis James , Abella Benjamin , McNally Bryan , Granger Christopher B.
Published: March 2022

Introduction:
Guidelines recommend implementation of regional systems of care for out-of-hospital cardiac arrest (OHCA) patients. Whether direct transport of OHCA patients to a PCI center over a non-PCI center improves outcomes is unknown.

Hypothesis:
Direct transport to a PCI center is associated with better outcomes.

Methods:
Using the Cardiac Arrest Registry to Enhance Survival, we identified OHCA patients with pre-hospital return of spontaneous circulation (ROSC) from 16 counties (population 3,143,809) in North Carolina between 2012-2014. Destination hospital was classified by PCI center status. We performed logistic regression analyses using propensity score inverse probability weights including drive time to nearest PCI center, initial rhythm and prehospital ECG information.

Results:
Of 1508 patients with ROSC, 1360 (90.2%) were transported to a PCI center and 148 (9.8%) to a non-PCI center (Table). The unadjusted survival rate was higher among those directly transported to a PCI center (33.5% versus 14.6%), OR 2.95 (95% CI 1.84-4.76). After accounting for potential confounding using inverse probability weights as well as adjusting for age, sex, EMS response time and clustering of county, direct transport to PCI center remained significantly associated with better survival, OR 2.47 (95% CI 2.08-2.92). Significant differences in survival remained when including patients without ST-elevation myocardial infarction only, adjusted OR 1.74 (95% CI 1.05-2.91). For patients bypassing the nearest hospital and taken directly to a PCI center with >10 min of difference in drive time between nearest hospital and PCI center, adjusted OR was 2.54 (95% CI 2.01-3.23) compared to patients taken to non-PCI hospitals.

Conclusions:
Direct transport to a PCI center appears to be associated with improved survival in OHCA patients. This suggests that implementation of protocols to transport patients with OHCA directly to PCI centers, when feasible, may improve outcomes.
Abstract 18394: Predicting Value of Platelet Reactivity on Bleeding and Major Adverse Cardiac Events in Eastern Asian PCI Patients
Authors: Wang Wenyao , Zhang Kuo , Yang Yuejin , Tang Yi-Da
Published: March 2022

Introduction:
Previous studies have shown that high and low platelet reactivity (HPR and LPR respectively) are associated with adverse events following percutaneous coronary intervention (PCI), however, therapy windows were not consistent in different studies. We aimed to determine the optimal cutoff value of platelet reactivity to prevent major adverse cardiac events (MACE) and bleeding in eastern Asian PCI patients.

Methods:
Consecutive 6266 non-emergent PCI patients with aspirin and clopidogrel therapy were enrolled prospectively in the single-center, large-volume investigation from January to December 2013. Platelet reactivity (ADP-induced platelet-fibrin clot strength [MAADP]) was determined by thrombelastography. MACE and Bleeding Academic Research Consortium (BARC) classification≥2 bleeding were assessed between different categories of platelet reactivity and Syntax Score (SS).

Results:
Overall, 475 MACE and 152 major bleeding (BARC grade≥2) events were recorded during one year follow-up. With receiver operating characteristic (ROC) curve, we determined the cutoff values of MAADP for MACE and major bleeding (45 mm and 34mm, respectively). Then, patients were classified according to MAADP (>45 mm, 34-45 mm, and <34 mm) and we evaluated the impact of platelet reactivity on MACE and major bleeding in different Syntax Score subgroups (SS45 mm was the predictor of MACE (HR: 2.3; 95%CI: 1.6-5.9), but MAADP45 mm was still the predictor of MACE (HR: 2.6; 95%CI: 1.3-6.3), while MAADP<34 mm show significant impact on major bleeding (HR: 1.8; 95%CI: 1.2-4.7).

Conclusions:
Platelet reactivity measured by thrombelastography could predict MACE and major bleeding in elective PCI patients, especially in those with high SS. Therapy window of anti-platelet drugs is narrow in eastern Asian population and further studies on tailored treatment of high-risk patients are needed.