tbuckley/cabot-search huggingface dataset:
Abstract 16682: Abnormal Left Ventricular Deformation in Mitral Valve Prolapse
Authors: Angelica Romero Daza, Aalap Chokshi, Patricia Pardo Martinez, Nicolas Maneiro Melon, Gina LaRocca, Matthew Cham, Adam H Jacobi, Michael S Chung, Leticia Fernández Friera, Jorge Solis Martin, Javier Sanz
Journal: Circulation (2018)

Background: Mitral valve (MV) prolapse (MVP) is usually considered a primary valvular abnormality. We hypothesized that there are concomitant abnormalities in regional left ventricular (LV) function in this syndrome. Objective: To characterize LV global and regional strain in MVP with and without significant mitral regurgitation (MR), defined as regurgitant fraction &gt;15%, in comparison with controls using cardiac magnetic resonance (CMR). Methods: A total of 109 MVP patients (median age 51 years, 40% males) with normal LV ejection fraction, and a control group of 45 patients (47 years, 53% males) without structural heart disease by CMR were retrospectively included. From standard cine images we quantified LV volumes and ejection fraction and, using feature tracking, global and segmental longitudinal and circumferential peak systolic strains. Results: Significant MR was found in 49 (44%) of MVP patients. Compared with controls, MVP patients had significantly higher LV end-diastolic and end-systolic volumes without differences in ejection fraction (Table). While there were no differences in global strains, regional longitudinal and circumferential peak systolic strains were increased in the basal anterior and anterolateral segments, and reduced in the mid inferior segment (Table). When comparing only patients without significant MR with controls, these differences remained significant (Table). Conclusions: In patients with MVP and normal LV ejection fraction there is LV dilatation and increased basal anterior and anterolateral deformation in comparison with controls, even in the absence of significant MR. These findings suggest that MVP may be a disease not only of the MV but also of the adjacent myocardium.
Abstract 16822: Endothelial c-Myc Protects the Heart From Pro-Inflammatory Changes During Aging and Atherogenic Stress
Authors: Yue Qi, Mariana T Pinto, Victoria Florea, Roberta Lassance-Soares, Claudia O Rodrigues
Journal: Circulation (2018)

Background: Inflammation plays an important role in cardiac remodeling and occurs in response to risk factors such as aging and high-fat diet (HFD). We have recently reported that c-Myc knockdown in endothelial cells triggers a senescence-associated pro-inflammatory phenotype. We found that c-Myc expression declines in human coronary artery endothelial cells (HCAECs) during replicative senescence and aging. These findings suggest that threshold levels of c-Myc in endothelial cells are required to protect the heart. Here we investigated the impact of endothelial c-Myc in the heart during aging and exposure to HFD using a transgenic mouse model with endothelial-specific c-Myc overexpression. Methods and Results: Gene expression profiling and pathway analysis of young (2-month) and old (10-month) mice showed that endothelial c-Myc overexpression has a protective effect, increasing the expression of genes that prevent cardiac hypertrophy such as Rgs2, Braf and Ppargc1a and reducing inflammatory mediators such as S100a9 and Ptx3. We validated the expression of inflammatory markers IL-1β, Cxcl1 and TGF-β2 by qPCR and found that in aged group, their expression was downregulated in transgenic mice by 2.46 (p&lt;0.002), 2.92 (p&lt;0.001) and 1.85 (p&lt;0.001) fold, respectively, relative to control mice. We further explored this novel protective role of c-Myc in the context of HFD using pre-designed Taqman stress array. Results showed significant downregulation of genes involved in oxidative stress (Noxo1, -1.72-fold, p&lt;0.01), autophagy (Tfeb, -1.72-fold, p=0.03) and DNA repair (Bub1b, -1.37-fold, p=0.02) in transgenic mice under control diet. In response to HFD, most stress genes were downregulated in control mice while a specific group was upregulated in transgenic animals, including genes involved in autophagy (Tfeb, 1.39-fold, p=0.06) and antioxidant pathways (Txnrd2, 1.58-fold, p=0.03; Msra, 1.72-fold, p=0.04 and Msrb3, 1.47-fold, p=0.05). Conclusion: Our c-Myc overexpression mouse model exhibits a distinct gene expression pattern that is potentially cardiac protective in response to aging and HFD. Endothelial c-Myc may be essential to protect cardiac tissues under stress conditions.
Abstract 16618: Prognostic Significance of Coronary Artery Calcium (CAC) Score among Patients on Statin Therapy: Results of Coronary Artery Calcium Consortium, a Multicenter Cohort Study
Authors: Hassan Mirbolouk, Paniz Charkhchi, S M Ifthekhar Uddin, Olusola A. Orimoloye, Leslee Shaw, Daniel S. Berman, Seamus Whelton, Zeina Dardari, Michael D Miedema, Matthew Buddof, John A Rumberger, Khurram Nasir, Michael J Blaha
Journal: Circulation (2018)

Introduction: Statins do not decrease coronary calcification, and may, in fact, increase calcification or its density. This has led some observers to question the value of coronary artery calcium (CAC) in patients taking statins. We, therefore, examined the cardiovascular prognostic significance of CAC among patients who are already on statin therapy. Methods: We included 6,815 patients who were taking statin at baseline from the Coronary Artery Calcium Consortium. We used Cox regression models to assess the association of CAC with cardiovascular disease (CVD) mortality using CAC as a continuous variable (1 unit increase in log-transformed CAC score) and categorical variable: CAC = 0 (reference), CAC=1-99, CAC=100-399, and CAC ≥400. Models were adjusted for age, sex, family history of CHD, smoking status, hypertension, and diabetes. Results: Patients (mean [SD] age 57.2 [10.4]years, 71.8% men) were followed for a median of 10.8 years. During this follow-up period, 140 participants died of CVD. One unit increase in log CAC score was associated with significantly increased risk of CVD mortality (hazard ratio (HR), 1.09; 95% CI = 1.07-1.11). Compared to CAC=0, CAC groups showed a graded increase point estimates of CVD mortality risk (P for trend &lt;0.001) (Table 1) , with those with CAC score ≥400 attaining statistical significance (2.5-fold increased risk). Conclusion: CAC scores remain a strong predictor of CVD mortality among asymptomatic patients who are taking statin. As such, there is likely a role for CAC to guide the intensity of LDL lowering or other preventive therapies in those already taking a statin.
Abstract 11981: Prognostic Value of Liver Stiffness Measurement in Patients Undergoing Left-Sided Valvular Surgery
Authors: Si-Yeung Yu, Hang Long Li, Yi Kei Stephanie Tse, Qingwen Ren, Meizhen Wu, Kwan Yu LI, Pui-Fai Wong, Lok Yee Jane Lam, Shuk Yin Yu, Kai Hang Yiu
Journal: Circulation (2021)

Introduction: Hepatic fibrosis is a recognised extracardiac manifestation of advanced heart diseases. The assessment of cardiac hepatopathies with non-invasive tools such as FibroScan(®) has shown promising prognostic value in patients undergoing right-sided valvular surgery. While an increased level of liver stiffness has been observed in patients with left-sided heart failure (HF), the prognostic value of liver stiffness measurement (LSM) remains unknown in patients undergoing left-sided valvular surgeries. Methods: Pre-operative LSM were taken from 239 patients undergoing left-sided valvular surgery prospectively between February 2013 and March 2021 using FibroScan(®). Patients were followed up for adverse outcomes, including mortality or HF requiring hospitalisation. Clinical parameters were collected and patients’ EuroSCORE II were calculated. The prognostic value of LSM for mortality was determined by Cox proportional-hazards regression adjusted for EuroSCORE II; whereas the Fine-and-Gray method was used to assess the prognostic value for (HF) for taking mortality into account as a competing risk. Any incremental value to EuroSCORE II was assessed by continuous net reclassification (cNRI) and integrated discrimination improvement (IDI) indicies. Results: Over a median follow-up of 4.1 years, 20 patients died and 28 were hospitalized for HF. LSM was an independent predictor of mortality (hazard ratio [HR]=1.07, 95%CI 1.04-1.10) and provided incremental prognostic value when added to EuroSCORE II (cNRI=0.17, 95%CI 0.02-0.34; IDI=0.39, 95%CI 0.14-0.66). LSM was predictive of subsequent HF (subdistribution HR=1.04, 95% CI 1.01-1.06) whereas EuroSCORE II was not. Conclusion: Pre-operative LSM negatively affects long term outcomes in patients undergoing left-sided valvular surgery.
Abstract 16795: A Trans-Ventricular Restraint to Reshape and Reduce the Left Ventricle Halts Chronic Adverse Remodeling in a Rodent Model of Ischemic Cardiomyopathy
Authors: Daisuke Onohara, Roberto Hernandez-Merlo, Daniella Corporan, Robert A Guyton, Muralidhar Padala
Journal: Circulation (2018)

Introduction: Elevated wall stress (WS) from chamber dilatation and wall thinning drive cause congestive heart failure(CHF) after a myocardial infarction(MI). Reducing WS by reshaping the left ventricle (LV) could decelerate or halt CHF progression, delaying need for ventricular assist devices or transplantation. In this study, we sought to investigate if a transventricular reshaping device (TRD - Fig 1A,B ) can preserve cardiac function and inhibit adverse remodeling in a rodent model of chronic ischemic cardiomyopathy. Hypothesis: Reducing left ventricular WS and sphericity index (SI) can preserve cardiac function and inhibit adverse remodeling in ischemic cardiomyopathy. Methods: Rats (n=18) were induced with an MI by left coronary artery ligation. 3 weeks post-MI, TRD was implanted on a beating heart in 9 rats (MI+TRD) ( Fig 2A-C ) and no surgery in others (MI only).TRD was tightened with echo, for 25% reduction in end-diastolic diameter and in WS. All rats were survived for another 3 weeks, with echo at 0, 2, 4, 6 weeks post-MI, and invasive hemodynamics at termination. Tissue was snap frozen for RNA-seq analysis. Results: Cardiac dysfunction were confirmed in both groups prior to TRD implantation (%EF in MI+TRD: 77.4±1.2vs. 59.6±2.1; p&lt;0.0001; %EF in MI: 74.7±1.8 vs. 57.0±3.3; p=0.0002 ). TRD implantation and tightening, reduced LVEDD from 8.7±0.2mm to 6.7±0.2mm (23% change, p &lt;0.0001), reduced sphericity index from 0.74±0.04 to 0.54±0.05 (27% reduction, p&lt;0.0001), and WS from 19.9±2.0 to 14.5±1.7 (27% decrease, p=0.0662) ( Fig 3A-B ). At termination, EDV and ESV were significantly reduced in MI+TRD compared to MI alone (EDV: 647.5±39.0μl vs 500.1±14.4μl; p=0.0032; 317.5±16.9 μl vs 218.1±14.7 μl; p=0.0021), indicating halted adverse remodeling with TRD ( Fig 4A-B ). Infarct border zone wall thickness was preserved in MI+TRD, but significantly reduced/thinned in MI ( Fig 5A ), containing infarct expansion. Pre-load adjusted LV dp/dt(max), was significantly higher in MI+TRD compared to MI only ( Fig 5B ). Conclusions: Reshaping and reducing the ischemic LV with the transventricular restraint, improves cardiac contractility, preserves ventricular wall thickness and inhibits infarct expansion in this chronic rodent model of cardiomyopathy.
Abstract 16644: Independent Predictors of 30-Day Readmission After Acute Myocardial Infarction at a Large, Inner City Medical Center
Authors: Catherine Bennet, Oluwaseun Fashanu, Francoise Marvel, Curtis Leung, Amy Deutschendorf, Daniel Brotman, Gary Gerstenblith, Scott Berkowitz, Nisha Chandra-Strobos, Seth Martin
Journal: Circulation (2018)

Background: Acute myocardial infarction (AMI) accounts for one of the most common reasons for cardiovascular disease admission in the United States. Despite modern therapeutics, 15-20% of index admissions for AMI result in unplanned readmission within 30 days of discharge. In tailoring efforts to decrease AMI 30 day readmissions we sought to identify independent predictors for readmission. Methods: All 1771 patient discharges from Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center in fiscal years 2016 and 2017 with a primary discharge diagnosis of AMI were included. The age, sex, race, insurance status, aggregated AHRQ comorbidity count, concomitant diagnosis of specific comorbidities, discharging hospital, discharging service, destination at discharge, diagnosis (NSTEMI vs. STEMI), procedures during index admission and length of index admission for each discharge were recorded and odds ratios with 95% confidence intervals for 30 day readmission to a Maryland hospital were calculated. If a patient was readmitted to a Hopkins hospital the reason for readmission was recorded. Results: Of the 1771 patient discharges over the study period, 273 were excluded because the patient was not eligible for readmission in CMS reporting algorithms (i.e. same or next day transfer, death), had a planned readmission, or was &lt;18 years old. Of the remaining 1498 discharges, 264 (17.6%) were readmitted within 30 days. In a multivariable model, major independent predictors of 30 day readmission risk were high comorbidity burden (OR for 4-5 vs. 0-1 comorbidities: 3.27, 95% CI 1.55 - 6.88; OR for &amp;gt; 5 vs. 0-1 comorbidities: 6.86, 95% CI 3.2 -14.71) and leaving the hospital AMA (OR 3.77, 95% CI 1.63-8.72). In a separate model considering specific comorbidities, a concomitant diagnosis of CHF (OR 1.94, 95% CI 1.4-2.67), renal failure (OR 1.76, 95% CI 1.27-2.45), or depression (OR 1.61, 95% CI 1.12-2.33) were independent predictors of readmission risk. Of patients whose readmission diagnoses were known (n=143), the majority (n=75, 52.4%) were readmitted with cardiac diagnoses. The most prevalent cardiac readmission diagnoses were CHF (n=28), NSTEMI (n=25), and chest pain (n=15). Conclusions: In our large, inner city hospital system, patients with a greater number of comorbidities, in particular CHF, renal failure, or depression, were at significantly greater risk for 30 day readmission after AMI. Identifying high risk patient characteristics is an important first step in designing tailored, system-wide initiatives to reduce AMI readmissions.
Abstract 16637: Left Ventricular Mass Predicts Response to Cardiac Resynchronization Therapy in Men but Not Women
Authors: Chad C Ward, Hakeem Ayinde, Casey Adams, Oluwaseun Adeola, Josiah Zubairu, Christopher Dezorzi, James Hopson, Gardar Sigurdsson, Michael Giudici
Journal: Circulation (2018)

Introduction: The effect of left ventricular mass (LVM) on response to cardiac resynchronization therapy (CRT) is not well known. Hypothesis: We hypothesize that baseline LVM would be positively associated with improved CRT outcomes. Methods: We retrospectively studied 343 consecutive patients who received CRT at our institution between 2008 and 2014. LVM was measured by echocardiography using the truncated ellipsoid method. Primary outcome was all-cause mortality. Secondary outcomes were (1) change in left ventricular ejection fraction (LVEF) by &gt; 5% at 6-12 months and (2) change in QRSd within 3 months. Results: There were 241 males and 102 females. Mean age at CRT implant was 63.6 ± 11.9 years. LVM was 366 ± 367g. Ischemic cardiomyopathy and left bundle branch block (LBBB) were present in 57% and 67% respectively. Fifty three percent of the study cohort had NYHA class III or IV at the time of implant. Death occurred in 36% of patients at a median follow up of 2.2 years. LVEF improved by &gt; 5% in 65% of patients at 6-12 months while QRSd decreased by a mean of 6.7 ± 27.8 ms within 3 months. The relationship between LVM and CRT response appeared to be strongly sex-specific. Higher LVM was associated with reduced mortality in men when LVM was used as a continuous and categorical variable dichotomized at the 75th percentile ([OR 0.999 (0.998-1.0000; p=0.068)] and [OR 0.47 (0.23-1.00; p=0.05)] respectively). There was no association in women (p=0.826). Higher LVM predicted improvement in LVEF in men [OR 0.99898 (0.9983-0.9997; p=0.005)] but not in women (p=0.324). Men with higher LVM experienced greater reduction in QRSd [OR 1.0015 (1.0006-1.0024; p=0.001)]. Again, there was no association in women (p=0.322). The relationship between LVM and change in both LVEF and QRSd remained significant and sex-specific after adjusting for age, LBBB, ischemic cardiomyopathy and atrial fibrillation (OR 0.99904, p=0.039 and OR 1.001, p=0.028 respectively in men). Conclusions: Left ventricular mass is an independent predictor of CRT outcomes in men but not in women. In males, greater left ventricular mass predicted improvement in LVEF as well as reduction in QRSd. This remained significant after adjusting for age, LBBB, ischemic cardiomyopathy, and atrial fibrillation.
Abstract 16731: Novel CMR Anatomical Predictors of Mitral Regurgitation Presence and Severity in Mitral Valve Prolapse
Authors: Aalap Chokshi, Angelica Romero Daza, Patricia Pardo Marinez, Nicolas Maneiro Melon, Adam Jacobi, Michael Chung, Matthew Cham, Gina LaRocca, Jorge Solis Martin, Leticia Fernández Friera, Javier Sanz
Journal: Circulation (2018)

Introduction: Mitral valve (MV) prolapse (MVP) is often associated with mitral regurgitation (MR). The determinants of MR in MVP are incompletely understood. Methods: We retrospectively identified 86 consecutive patients with MVP and preserved ejection fraction undergoing CMR with velocity encoding for MR quantification between 2005 and 2017. On 3-chamber cine images we measured, in end-diastole (Figure), end-systole, and their percentage change during the cardiac cycle, the following parameters: basal and mid inferolateral wall thickness, posterior papillary muscle length, annulus diameter, LV diameter and distance from the posterior papillary muscle to anterior and posterior annulus. In addition, we measured anterior and posterior leaflet thickness in diastole and maximal prolapse distance in end-systole. We explored the associations between these parameters and mitral regurgitant fraction (RF) using multivariate linear regression. Results: Median age was 52.6 years and 48% were males. There was posterior MVP in 49 (57%), bileaflet MVP in 35 (41%) patients, and isolated anterior MVP in 2 (2%) patients. MR was present in 73 (85%) and, in these, median RF was 23% (IQR 13-33%). In multivariate analyses, diastolic papillary muscle to posterior annulus distance, maximal prolapse distance, maximal posterior leaflet thickness, and LV basal inferolateral diastolic thickness were independent predictors of mitral RF (p&lt;0.05 for all). Conclusions: Beyond known determinants of MR in MVP such as maximal prolapse and leaflet thickness, we identified novel anatomical predictors of MR severity, namely increased diastolic papillary muscle to posterior annulus distance and LV basal inferolateral thickness. Whether these abnormalities represent secondary changes to MVP (i.e. basal inferolateral “stretch” and compensatory regional LV hypertrophy, respectively) or primary phenotypic features of the MVP syndrome is uncertain.
Abstract 16817: Single Anti Platelet Agent vs. Dual Anti Platelet Agents in Patients Undergoing Percutaneous Coronary Intervention: A Tertiary Care Center Experience
Authors: Shilpkumar Arora, Safi U Khan, Mihir Dave, Sudhakar Sattur
Journal: Circulation (2018)

Introduction: Data on P2Y12 inhibitor (single agent) use in percutaneous coronary intervention (PCI) is sparse. Hypothesis: Long term outcomes in patients undergoing PCI with only P2Y12 inhibitors vs. dual antiplatelet therapy (DAPT). Methods: We used PCI registry of Guthrie clinic system from the year 2001 to 2012. We identified patients discharged only on P2Y12 inhibitors (Plavix, Ticagrelor, Prasugrel) due to aspirin allergy. We created propensity score using patient demographics (age, gender), risk factors (hypertension, diabetes, hyperlipidemia etc.), medications detail (statin, B blocker etc.) and catheterization detail (vessel involved, type of stent and culprit vessel etc.) for patients discharged only on P2Y12 inhibitors vs DAPT. Propensity score match (1:100) analysis was conducted using greedy’s method for adjusting confounders. The primary outcome was MACE(myocardial infarction(MI), stroke, death, coronary artery occlusion) up to 8 years and secondary outcomes were death and recurrent myocardial infarction(MI) up to 8 years. Sensitivity analysis was done using Cox-proportional hazard regression. Results: 7742 patients with successful intervention were identified during the study period. Out of which, 43(0.65%) had aspirin allergy and received only P2Y12 inhibitor. Hyperlipidemia (78.8%), hypertension (72.8%), obesity (48.7%) and diabetes (31.6%) were most common risk factors. &gt;90% patients were on optimum medical treatment. 59% of patients received drug-eluting stent/s and 17.5% patients underwent multivessel PCI. Right coronary artery(37.6%) and left anterior descending artery(35.8%) were commonest culprit vessels. Median follow up period was 1828 days (~ 5 years). After adjusting with propensity score match, primary outcome (HR:1.73, 95% CI: 1.17-2.67, p-0.005) and secondary outcomes (MI: HR: 2.46, 95% CI:1.28-4.51, p-0.005), (death: HR:1.85, 95% CI:1.09-2.23, p-0.023) were higher in patients discharged only on P2Y12 inhibitors. Sensitivity analysis showed similar results. Conclusions: Only P2Y12 inhibitor was inferior to DAPT in patients undergoing PCI. Future clinical trials will be needed to reinforce our findings.
Abstract 16656: How to Routinely Obtain One Billion Human Cardiomyocytes: A Large-Scale Systematic Expansion of Pluripotent Stem Cells and Differentiation Into Cardiomyocytes
Authors: Fernanda C P Mesquita, Camila Hochman-Mendez, Yutao Xi, Helen A Andersson, Jacquelynn Morrissey, Luiz C Sampaio, Doris A Taylor
Journal: Circulation (2018)

Background: Tissue engineering a human-sized whole heart requires recellularization of a scaffold with billions of cardiomyocytes, which are post-mitotic cells with limited expansion capability. Induced pluripotent stem cells (iPSCs) provide a new opportunity for cardiac tissue engineering, because iPSCs can be expanded and differentiated into cardiomyocytes. A closed cell culture system is an efficient clinically applicable tool that can be used to expand cells under controlled conditions. We used the Quantum Cell Expansion System (QES) as a human iPSC expansion platform. Methods: Human iPSCs were expanded 30-fold using the QES and karyotyped. The undifferentiated cells were characterized by RT-PCR, immunofluorescence and their ability to undergo spontaneous differentiation. After harvesting, iPSCs were differentiated into the cardiac lineage, and the cardiomyocytes were characterized by RT-PCR, immunofluorescence and flow cytometry. Action potential recordings were obtained through intracellular impalement (MultiClamp 700). Results: The QES provided the necessary environment for exponential iPSC growth, reaching 70.9x10e7 ± 20,75 x10e7 cells in less than 7 days (n=4), with a population doubling of 3.801 ± 0.1956. The cells kept a normal karyotype (46-XX), expressed pluripotency markers (OCT4, NANOG, LIN28, SOX2, REX1, DNMT3B, DPPA4, NODAL, TDGFb, TERT3, and GDF) and had characteristic staining for OCT4, SOX2, NANOG, SSEA4, TRA1-60, and TRA1-81. Spontaneous differentiation into ectoderm (NESTIN, TUBB3, and NEFH), mesoderm (MSX1, BMP4, and T) and endoderm (GATA6, AFP, and SOX17) lineages was detected by RT-PCR. Induction to the cardiac lineage was also characterized [cTNT+ by flow cytometry (with an efficiency of 74.2±6.3%, n=5) and immunohistochemistry, and MYH6, MYH7, MLC2a, MLC2V, KCNA5, KCNQ1, KCNJ3 by RT-PCR]. Electrophysiology analysis demonstrated that the action potential duration with 90% of repolarization (cAPD90) was 506.5 ± 27.99 mV and the beating rate of these cells was 39.08±1.8 bpm (n=31). Conclusion: QES maintains the stemness of iPSCs and is a promising platform to provide the high numbers of cardiomyocytes necessary to recellularize human-sized heart scaffolds.