tbuckley/cabot-search huggingface dataset:
Abstract 16621: Holter Monitoring in Patients With Left Ventricular Noncompaction
Authors: Medhat Farwati, Vaibhav R Vaidya, Ameesh Isath, Melissa Lyle, Samuel J Asirvatham, Abhishek J Deshmukh, Thomas Foley, Hector Michelena, Heidi M Connolly, Rowlens M Melduni, Suraj Kapa
Journal: Circulation (2018)

Introduction: Multiple arrhythmias including ventricular tachycardia (VT) and atrial fibrillation (AF) have been reported in patients with left ventricular noncompaction (LVNC). We sought to determine the frequency of rhythm abnormalities on Holter monitoring, and their association with all-cause mortality, in patients with LVNC. Methods: Imaging databases from 2000-2016 were reviewed to identify patients with LVNC. On transthoracic echocardiography (TTE), LVNC was defined as: end systolic noncompacted: compacted (NC:C) ratio&gt;2 and end diastolic epicardium to trough: epicardium to peak trabeculation (X:Y) ratio&lt;0.5. Holter monitor reports from the medical record were evaluated. VT was defined as ≥3 consecutive beats of ventricular origin. All-cause mortality was obtained from a web-based research and location service (Accurint). We used a proportional hazards model to determine associations of Holter variables with all-cause mortality. Results: Among 340 LVNC patients, Holter reports were available for 177 patients (median age 45 years, interquartile range [IQR] 33-61; 45% females). On TTE, the median NC:C ratio was 2.7 (IQR 2.4-3.2) and X:Y ratio was 0.25 (IQR 0.20-0.28). The median ejection fraction (EF) was 48% (IQR 33-58). 48 patients (27%) had at least one episode of VT (median 4 episodes, IQR 2-4). The median longest duration of VT was 5 beats (IQR 4-9) and maximum rate was 148 beats per minute (IQR: 125-169). PVC burden &gt;5% and 20% was present in 13% and 5% of patients respectively. Patients with EF&lt;50% were more likely to have VT (43% vs 16%, p=0.0003) and PVC burden &gt;5% (19% vs 7%, p=0.03). AF was infrequent (N=5, all persistent). All-cause mortality was 12% over median 6.9 years of follow up (IQR: 3.6-11.3 years). Presence of VT and PVC burden on Holter monitoring were not associated with all-cause mortality (p&gt;0.05). Among patients with VT, the number, longest duration, and fastest rate of VT episodes were not associated with all-cause mortality. Conclusions: Ventricular tachycardia on Holter monitoring is common among patients with LVNC, especially those with a reduced EF. However, the clinical significance of this finding is uncertain, and presence of VT was not associated with long term all-cause mortality.
Abstract 13711: End-Stage Renal Failure and Bleeding Complications in Patients Undergoing Percutaneous Coronary Intervention: A Contemporary System-Wide Analysis
Authors: Tia Bimal, Md Bhuiyan, Puneet Gandotra, Gregory Haggerty, Samy Selim, Lawrence Ong, Luis Gruberg
Journal: Circulation (2021)

Background: Patients with chronic kidney disease (CKD) and significant impairment of kidney function (eGFR of 15-29 ml/min/1.73m 2 ) ( CKD Stage G4 ) and patients with an eGFR of &lt;15 ml/min/1.73m 2 , or who require some form of dialysis (CKD Stage G5) are often referred to as end-stage renal failure (ESRF) . These patients tend to have more severe coronary disease and worse outcomes following percutaneous coronary intervention (PCI). Aim: To compare the in-hospital bleeding complications and major adverse cardiac and cerebrovascular (MACCE) events in CKD Stage G4 with CKD Stage G5 (dialysis) patients undergoing PCI. Methods: Between 12/2010 and 03/2018 a total of 1,534 ESRF patients underwent PCI at 6 hospitals in our system. Patients were divided into two groups, those with an CKD Stage G4 (n=954) and those on dialysis CKD Stage G5 (n=580). Bleeding complications were classified according to Bleeding Academic Research Consortium (BARC). BARC 4 (coronary bypass grafting-related bleed) and BARC 5 (fatal) bleeding events were excluded. Chi square statistical analysis was used for categorical values and t-test for continuous variables. P&lt;0.05 was considered significant. Results: Clinical characteristics, bleeding complications, and in-hospital outcomes are shown in the Table. Patients with CKD Stage G4 were older, had a higher percentage of female patients and more often presented with a STEMI when compared with CKD Stage 5 (dialysis) patients. Bleeding (BARC ≤2 and 3) rates were similar between the two groups. Although mortality and MACCE (Death/MI/Stroke/Major Bleed) rates were numerically higher in Stage G4 patients, it did not reach statistical significance. Conclusion: In a contemporary analysis of ESRF patients undergoing PCI, CKD Stage G4 and CKD Stage G5 (dialysis) patients had low and comparable rates of moderate and severe bleeding complications. Furthermore, in hospital MACCE rates were low and similar in these two groups.
Abstract 16750: Angiogenesis/Arteriogenesis, the Mechanism for Cardioprotection, in Secreted Frizzled Related Protein 2 Transgenic Mice
Authors: Marko Oydanich, Jie Zhang, Seonghun Yoon, Dorothey E Vatner, Stephen F Vatner
Journal: Circulation (2018)

Secreted frizzled related protein 2 (sFRP2) has been shown to protect against myocardial ischemia primarily mediated by reducing fibrosis. Our hypothesis is that sFRP2 myocardial ischemic protection induced by permanent coronary artery occlusion (CAO) must involve a primary angiogenesis/arteriogenesis mechanism in order to protect the heart in the chronic absence of blood flow. To test this hypothesis, we induced permanent CAO for 1 week in cardiac specific sFRP2 transgenic (TG) mice (n=12), which exhibited reduced infarct size vs. their wild type littermates (WTL; n=13) (16±1 vs. 25±2%) and improved left ventricular ejection fraction (LVEF) (61±6 vs. 45±6%). These salutary effects were accompanied by angiogenesis (170% increase in capillary proliferation and a 54% increase in capillary density) and arteriogenesis (106% increase in arteriole proliferation). sFRP2 increased in vitro tubule formation in HUVEC cells by 46% (p&lt;0.05), compared to vehicle. As expected, sFRP2 TG mice also exhibited decreased remote fibrosis, compared to WTL (1.6±0.1 vs.± 3.7±0.3%; n=4-6/group). ATF6, an ER stress response transcription factor, was upregulated in sFRP2 TG mice. When ATF6 was blocked with AEBSF, sFRP2 TG mice no longer demonstrated cardioprotection with permanent CAO, as reflected by similar infarct size, LV EF, capillary and arteriolar proliferation observed in WTL. cTGF, a pro-angiogenic factor, was also upregulated in sFRP2 TG mice. Blocking cTGF with a cTGF antibody, eliminated the increased tubule formation with sFRP2 treatment. AEBSF also eliminated the increased cTGF in sFRP2 TG, confirming ATF6 as the upstream regulator of cTGF, responsible for the angiogenesis and arteriogenesis observed in the sFRP2 TG mice. To determine if angiogenesis/arteriogenesis was the initiating mechanism inducing cardioprotection, blood flow, measured ultrasonically at 1 day following CAO, was increased significantly more, p&lt;0.05, in the ischemic zone of sFRP2 TG mice (2.1±0.46 A.U.) compared with blood flow in WTL (0.4 ±0.09 A.U.). Thus, angiogenesis/arteriogenesis appears to be the primary cardioprotective mechanism induced by sFRP2, with reduced fibrosis playing a secondary role.
Abstract 16874: Ablation of Ventricular Tachycardia is Associated With Improved Arrhythmia-Free Survival Among Patients With Severe Heart Failure
Authors: Natalie M Beck, Peter J Sauer, Alexis Z Tumolo, Amneet Sandhu, Matthew M Zipse, Ryan T Borne, Duy T Nguyen, Joseph L Schuller, Ryan G Aleong, Christine Tompkins, Paul D Varosy, Michael Rosenberg, Prateeti Khazanie, Natasha Altman, Andreas Brieke, William Cornwell, Eugene Wolfel, Amrut Ambardekar, Larry Allen, Wendy S Tzou
Journal: Circulation (2018)

Background: Ventricular tachycardia (VT) ablation is often avoided in patients with advanced heart failure (HF) and this group of patients is often excluded from research trials. Objective: To evaluate VT recurrence rates among patients with severe HF and VT treated with ablation (Abl) versus medications (Med) alone. Methods: We performed a retrospective analysis of patients presenting to a tertiary referral hospital between 2006 and 2017 with ventricular tachycardia and severe heart failure (New York Heart Association functional Class IV or any Interagency Registry for Mechanically Assisted Circulatory Support score) for whom electrophysiology consult was requested. Baseline characteristics and VT recurrence were compared based on method of arrhythmia treatment. Results: Of 129 patients, 47% underwent ablation while 53% were managed medically. In this cohort, mean age was 60 ± 12 years, 84% were males, ischemic cardiomyopathy was present in 55%, mean LVEF was 24±12%, and 77% had a preexisting ICD.One-year mortality was 23%, 40% of whom were treated with Abl versus 60% with Med, p=0.196. Abl patients were more likely to have an ICD prior to presentation (85% vs 69%, p=0.037) and had shorter length of hospital stay (14±16 vs 21±16 days, p=0.021) compared to Med patients. Other baseline characteristics were not significantly different between groups. Abl patients overall had better VT-free survival compared to those treated with medications alone (OR 0.36, 95% CI [0.18, 0.80], Figure). Conclusions: Ablation of ventricular arrhythmia even in patients with severe heart failure is associated with decreased length of hospitalization and improved VT-free survival compared to medical therapy alone. These findings warrant additional, prospective study to verify and possibly improve management of this high-risk group of patients.
Abstract 16924: Diagnostic Accuracy of Quantification Myocardial Perfusion Ratio Derived From Dynamic CT Perfusion Imaging for Detection of Functionally Significant Stenosis
Authors: Teruyoshi Uetani, Teruhito Kido, Yasuhisa Nakao, Yusuke Akazawa, Masaki Kinoshita, Fumiyasu Seike, Yasuhiro Sasaki, Haruhiko Higashi, Akira Fujii, Jun Aono, Takayuki Nagai, Kazuhisa Nishimura, Katsuji Inoue, Shuntaro Ikeda, Osamu Yamaguchi
Journal: Circulation (2018)

Introduction: Quantification perfusion ratio (QPR) is defined as the ratio between myocardial blood flow (MBF) in the stenosis-related territory and MBF in the non-stenosis-related territory derived from stress dynamic CT myocardial perfusion (CTP) imaging. Hypothesis: We sought to evaluate whether QPR can be used as a novel non-invasive method for detection of functionally significant coronary artery stenosis compared with fractional flow reserve (FFR). Methods: This study was retrospectively included 25 consecutive patients (32 vessels) with coronary artery disease and examined with CT angiography, CTP, coronary angiography, and FFR. QPR and stress MBF results were compared with invasive FFR using a threshold of 0.80. Results: The QPRvalues were significantly correlated to FFR values (R=0.865,P &lt;0.0001, Fig 1). The area under the receiver operator curve was larger for QPR (0.937) compared with stress MBF (0.812, Fig 2). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of QPR were 93.8%, 86.7%, 100%, 100%, and 89.5%, respectively. Conclusions: QPR was feasible and provided high diagnostic value for detecting abnormal FFR in patients with stable coronary artery disease.
Abstract 16809: Geographic Variations in Discharge Outcomes of Cardiac Arrest From 2011-2015: A Nationwide Analysis
Authors: Laura M Chen, Vivek Modi, Di Pan
Journal: Circulation (2018)

Objective: We investigated the discharge outcomes of patients with cardiac arrest across nine hospital divisions in the United States from 2011 to 2015. Methods: This is a retrospective analysis based on the 2011-2015 Nationwide Inpatient Sample (NIS) databases. Patients with a primary diagnosis of cardiac arrest and who received CPR were included. Multivariate logistic regression was performed to reveal variations in discharge outcomes over nine hospital divisions (New England (NE), Mid-Atlantic (MA), East North Central (ESC), West North Central, South Atlantic, East South Central, West South Central (WSC), Mountain, and Pacific). Diagnoses were identified with ICD-9 codes. The fourth quartile of 2015 NIS was excluded due to the transition to ICD-10 codes. Results: Hospitals in NE had fewer discharges home compared to divisions except in MA and ESC. NE had more discharges to short term hospitals (STH) compared to divisions except Pacific. NE had more discharges to skilled nursing facility (SNF) compared to MA and Pacific divisions. NE had fewer deaths compared to MA, ESC, and Pacific divisions. NE had more palliative care encounters compared to ESC and WSC divisions. Conclusions: Discharge outcomes of cardiac arrest patients varied by geography in the United States; NE hospitals had fewer discharges home and deaths, while had more discharges to STH and SNF. They also had higher palliative care encounters.
Abstract 16866: Sex Differences in Access to Care Before Acute Myocardial Infarction: Does the Health Care System Matter?
Authors: Valeria Raparelli, Louise Pilote, Harlan M Krumholz, Rachel P Dreyer
Journal: Circulation (2018)

Introduction: Access to high-quality health care for young women with acute myocardial infarction (AMI) lags behind that of men. Whether access to care varies based on the health care system remains unknown. We evaluated sex differences in pre-AMI access to care in young patients with AMI across countries. Methods: We utilized data from the GENESIS-PRAXY and VIRGO cohorts, which included young ( &lt; 55 yrs) AMI patients hospitalized in countries with public (Canada, Spain, Australia) or private (United States [US], Switzerland) health care systems (2009-13). We collected data on demographics, CV risk, and psychosocial factors. Pre-AMI access to care was defined as: having a primary health care provider, difficulties in access to primary/specialist care, primary health care visits/diagnostic tests for cardiac symptoms (12 months prior to AMI). Sex-stratified analysis by health care system was performed. Results: Among 4,689 AMI patients (58% women, mean age 47±6 yrs), 64% were from the US and 22% from Canada. Compared with men, women had more CV risk factors, higher rates of depression/stress and lower socioeconomic status (SES) (Table); more strikingly in the US. Across countries, 70% of patients had a primary health care provider. However, women experienced more difficulties accessing primary (21% vs. 15%) or specialist care (27% vs. 20%, all p&lt;.001) versus men. Women in the US reported cost barriers (47% vs. 5%), whereas women from other countries had difficulties in contacting primary health care providers (91% vs. 46%, all p&lt;.001). Nevertheless, compared with men, women reported more primary health care provider visits (46% vs. 37%) and tests for cardiac symptoms (66% vs. 50%), regardless of health care system. Conclusions: In both public and privately funded health care systems, one-fifth of young AMI patients had poor pre-AMI access to care, despite a high-risk factor burden - especially among women in the US. Young women of low SES should be targeted for primary prevention.
Abstract 16676: A-mhc MitoTimer Mouse Reveals Metabolic Heterogeneity in the Heart
Authors: Aleksandr B Stotland, Miroslava Stasna, Sarah J Parker, Jennifer van Eyk, Roberta A Gottlieb
Journal: Circulation (2018)

Introduction and hypothesis: To study mitochondrial turnover in the heart, we developed MitoTimer, a fluorescent protein targeted to the mitochondrial matrix that matures from green to red fluorescence over time. We generated a mouse line where MitoTimer is expressed under the cardiac-restricted promoter and were able to observe newly-synthesized and quiescent mitochondria in cardiomyocytes. Surprisingly, the hearts exhibit considerable heterogeneity in green-to-red MitoTimer fluorescence at the level of cardiomyocytes as well as between the mitochondria within individual cells. We hypothesized that these discrete subpopulations of cells represent fibers engaged in specialized functions. Methods: To isolate cells from the heart for proteomic and biochemical analysis, we developed an isolation strategy utilizing flow-cytometry followed by sequential processing to separate cytosolic, myofilament and insoluble protein fractions for liquid chromatography/mass spectrometry. Results of the analysis were validated by biochemical techniques. Results: Analysis of cardiomyocyte sub-populations revealed substantial differences in their protein compositions. Green cells display a profile consistent with an upregulation of PPARA and KLF15 signaling pathways and a downregulation of insulin receptor signaling, suggesting a preference for fatty acid oxidation (FAO). Consistent with this analysis, Western blots revealed that green cells express higher levels of CD36 and Cpt1b proteins compared to red cells. Interestingly, maturation of Timer protein fluorescence to red is sensitive to changes in molecular oxygen concentration. Cells that exhibit higher utilization of FAO and thus a lower oxygen tension will have a decrease in MitoTimer protein maturation, resulting in a greater green fluorescence. These results suggest MitoTimer may be a useful not only as a marker of mitochondrial age, but also as a marker of metabolic substrate preference. Conclusion: Cardiomyocytes in the heart present a highly heterogeneous population, arranged in discrete fibers that have a higher preference for one metabolic substrate over another. We are currently investigating the physiological roles these fibers play in the heart.
Abstract 16931: Alternate UTR Usage Regulates Connexin43 mRNA Translation Limiting Gap Junction Formation During Stress
Authors: Michael J Zeitz, Patrick J Calhoun, James W Smyth
Journal: Circulation (2018)

Introduction: Connexin43 (Cx43, Gja1 ) gap junctions enable electrical coupling of cardiomyocytes necessary for heart function. Pathological disruption of Cx43 expression or localization results in the arrhythmias of sudden cardiac death. Investigation of Cx43 gap junction biology has focused on transcription, vesicular trafficking, and post translational modifications. The importance of translational regulation however is highlighted by the recent discovery that Cx43 mRNA undergoes internal translation initiation to yield truncated protein isoforms, including the predominant GJA1-20k isoform capable of regulating gap junction formation. We have found that TGF-β signaling, a hallmark of cardiac stressors including hypertrophy, suppresses GJA1-20k expression to limit gap junction formation. The mechanisms regulating Cx43 mRNA internal translation in response to cellular stress are unknown but are critical in harnessing this biology for therapeutic restoration of electrical coupling in diseased hearts. We hypothesize that altered Gja1 -5’UTR usage promotes translation of full length Cx43 over internal translation products resulting in reduced gap junction formation during stress. Methods: Rapid amplification of cDNA ends was used to identify Gja1- 5’UTR isoforms following TGF-β exposure or hypoxia, and Western blotting was used to monitor Gja1 translation. Identified Gja1 -5’UTR variants were transfected into Cx43 knockout cells to assess translational potential. Luciferase assays assessed potential IRES activity within Gja1 mRNA in relation to specific 5’UTR isoforms. Results: TGF-β or hypoxia significantly increase translation of full length Cx43 over Gja1-20k correlating with an increase in truncated Gja1 -5’UTRs. Sequenced UTR isoforms map to genome wide transcription start sites and transfection of Gja1 transcripts with truncated 5’UTRs is sufficient to reduce Gja1-20k translation, phenocopying stress models. Conclusions: Alteration of Gja1 -5’UTR composition represents a powerful mechanism connecting alterations in transcription to gene-specific translational regulation to fine tune intercellular communication during stress.
Abstract 16851: Sinus Node Dysfunction Underlies Chronotropic Incompetence in Rats With Heart Failure and Preserved Ejection Fraction
Authors: Jae Hyung Cho, Rui Zhang, Joshua I Goldhaber, Eduardo Marbán, Eugenio Cingolani
Journal: Circulation (2018)

Introduction: Chronotropic incompetence is a major limiting factor of exercise capacity in patients with heart failure and preserved ejection fraction (HFpEF) but little is known about the mechanisms. Hypothesis: We tested the hypothesis that sinus node dysfunction underlies chronotropic incompetence in rats with HFpEF. Methods: Dahl salt-sensitive rats were fed high-salt diet (8% NaCl) to induce HFpEF. Rats fed normal-salt diet (0.3% NaCl) served as controls. Echocardiography was used to confirm the development of diastolic dysfunction in high-salt-fed rats. Telemetry devices were implanted to echo-verified HFpEF rats and treadmill exercise test was performed to assess heart rate response to exercise and exercise capacity. Sinus node recovery time (SNRT) was measured in vivo and ex vivo optical mapping was performed in isolated sinus node tissues to measure heart rate response to isoproterenol. Reverse transcriptase PCR was performed in RNA samples isolated from sinus node tissues. Results: HFpEF rats showed decreased E/A ratio (1.30±0.07 vs. 1.58±0.13, p&lt;0.05) and increased E/E’ ratio (19.17±2.63 vs. 13.78±2.58, p&lt;0.05) compared to controls, indicative of diastolic dysfunction. Ejection fractions were normal (71±7% vs. 73±3%, p=ns) in both groups. Resting blood pressure were elevated in HFpEF rats compared to controls (209±30/120±38 vs. 151±12/88±17 mmHg, p&lt;0.05) and serum catecholamine levels were elevated in HFpEF rats (38.4±5.6 vs. 25.6±1.5 ng/ml, p&lt;0.05). Heart rate at peak exercise was decreased in HFpEF rats compared to controls (496±21 vs. 538±20 bpm, p&lt;0.05) and exercise capacity was reduced in HFpEF rats (170±99 vs. 289±120 meters, p&lt;0.05). Corrected SNRT was prolonged in HFpEF rats (86±34 vs. 58±10 ms, p&lt;0.05), indicative of sinus node dysfunction. Ex vivo sinus node preparations showed decreased heart rate response to isoproterenol (119±12 vs. 163±27 bpm, p&lt;0.05). Beta-1 receptors gene expression ( Adrb1 ) were not decreased in HFpEF sinus node (93% in HFpEF vs. 100% in control, p=ns) nor were L-type Ca channels gene expression ( Cacna1c ) (95% in HFpEF vs. 100% in control, p=ns). However, pacemaker channels gene expression ( Hcn4 ) showed a trend toward reduction in HFpEF sinus nodes (60% in HFpEF vs. 100% in control, p=0.1). Conclusions: Sinus node dysfunction underlies chronotropic incompetence in rats with HFpEF. Further investigation is warranted to elucidate the mechanism and design potential therapeutic strategies for this condition.