tbuckley/cabot-search huggingface dataset:
Abstract 11716: The Impact of a Virtual Multi-Disciplinary Heart Failure Optimization Program on Achievement of Guideline-Directed Therapy
Authors: Avinash K Pandey, Nicolas Serafini, Ian Bonavie, A Shekhar Pandey
Journal: Circulation (2021)

Introduction: Current guidelines for management of Heart Failure with Reduced Ejection Fraction (HFrEF) recommend Beta-blockers, Angiotensin Receptor Neprilysin Inhibitors (ARNI), Mineralocorticoid Receptor Antagonists (MRA) and SGLT2 inhibitors. However, guideline-directed medical therapies (GDMT) remain underutilized. The 2018 CHAMP-HF registry of HFrEF patients demonstrated that only 1% of patients were treated with target doses of Beta-blockers, MRA and ACE-inhibitors (ACE-I) and Angiotensin Receptor Blocker (ARB) or ARNI. Methods: We conducted a single center study of a virtual, multidisciplinary HFrEF optimization program for achieving GDMT. Patients referred from both inpatient and outpatient settings were enrolled in this 3-month initiative. After an initial cardiology consult, patients were seen virtually once weekly by a kinesiologist for lifestyle optimization and virtually by a nurse once every two weeks for up-titration of guideline-based therapies, with cardiologist oversight. Vital signs, serum creatinine and electrolytes were obtained after medication adjustment. Results: Over 9 months, 297 patients were referred and all enrolled in the virtual HFrEF optimization program. Mean age was 69 and 63% were male. Mean ejection fraction was 28% and 54% had ischemic cardiomyopathy. At initial visit, the frequency of patients prescribed optimal dosage for Beta-Blockers was 64%, 7% for MRA and 1% for SGLT2 inhibitors. 88% were prescribed ACE-I or ARB while 1% of patients were on ARNI. At 3 month follow-up, the frequency of patients prescribed optimal dosage for Beta-Blockers was 84% (p&lt;0.01), 58% for MRA (p&lt;0.01), 77% for SGLT2 inhibitors (p&lt;0.01) and 96% for ARNI (p&lt;0.01). Overall, 39% of patients achieved maximal doses of all 4 classes of medications at 3 month follow-up. During the study period, there were no hospitalizations or medication adverse events among participants. The most common causes of failure to achieve GDMT was chronic kidney disease or drug cost or coverage. Conclusions: This study demonstrates that a virtual multidisciplinary program can safely and effectively improve usage of GDMT in HFrEF patients. Further studies should examine the effect of similar interventions on patient outcomes in a randomized format.
Abstract 10058: Increased Prevalence and Worsened Outcomes of Peripheral Vascular Disorders Hospitalizations in Young Adults: A National Decade Apart Analysis, 2007 vs. 2017
Authors: Rupak Desai, Harika Varma Chintalapalli Patta, Priya Shenwai, Sashwath Srikanth, Nibras Yar Khan, Taherunnisa Rida, Ummul Asfeen, Zainab J Gandhi, Akhil Jain
Journal: Circulation (2021)

Background: Prevalence and trends in peripheral vascular disease (PVD) admissions among young adults have been infrequently evaluated on a large scale. We aimed to study the demographics, comorbidities, and outcomes of PVD in young adults from data selected from two nationwide cohorts a decade apart (2007 vs 2017). Methods: We queried National Inpatient Sample (2007 &amp; 2017) to identify PVD admissions among young adults (18-44 years) and compare the burden, demographics, comorbidities between 2017 and 2007 cohorts. Primary outcomes were all cause mortality, MACE (all-cause mortality, AMI, cardiogenic shock, cardiac arrest, ventricular fibrillation/flutter, pulmonary embolism, coronary intervention) and stroke, and secondary outcomes were hospital resource utilization. Results: There was an increase in young PVD hospitalizations in 2017 (0.5%/n=46,760) vs. 2007 (0.4% /n=37,099). The 2017 cohort often included younger (37 vs 40 years), white (54.8% vs 57.7%), female (48.6% vs 47.5%), Medicaid enrollees admitted non-electively (85.2% vs 80.0%) (p&lt;0.05) vs. 2007 cohort. Comorbidities like smoking, drug abuse, fluid and electrolyte disorders, and pulmonary circulation disorders were the most frequent comorbidities in 2017 cohort vs. 2007 cohort. Despite lower rate of hypertension, renal failure, hyperlipidemia, complicated diabetes decreased in young PVD admissions from 2007 to 2017 (p&lt;0.001), there was alarming increase in all-cause mortality (1.5% vs 3.4%, aOR1.39, 95%CI:1.23-1.59) and stroke (4.2% vs. 10.4%, aOR2.43, 95%CI:2.25-2.63) on adjusted multivariable analysis (p&lt;0.001) with comparable MACE (8.9% vs 10.4%, aOR0.99, p=0.697) in 2017 vs. 2007. There was fewer routine discharges, prolonged hospital stay and charges in 2017 PVD cohort. Conclusion: The comparison of two national cohorts selected a decade apart showed an increased frequency of admissions of young PVD with higher substance abuse and higher all-cause mortality and stroke.
DropletQC: improved identification of empty droplets and damaged cells in single-cell RNA-seq data
Authors: Walter Muskovic, Joseph E. Powell
Journal: Genome biology (2021)

Advances in droplet-based single-cell RNA-sequencing (scRNA-seq) have dramatically increased throughput, allowing tens of thousands of cells to be routinely sequenced in a single experiment. In addition to cells, droplets capture cell-free "ambient" RNA predominantly caused by lysis of cells during sample preparation. Samples with high ambient RNA concentration can create challenges in accurately distinguishing cell-containing droplets and droplets containing ambient RNA. Current methods to separate these groups often retain a significant number of droplets that do not contain cells or empty droplets. Additionally, there are currently no methods available to detect droplets containing damaged cells, which comprise partially lysed cells, the original source of the ambient RNA.
Oral Carbon Monoxide Therapy in Murine Models of Sickle Cell Disease: Beneficial Effects on Vaso-Occlusion, Inflammation and Anemia
Authors: John D Belcher, Edward Gomperts, Julia Nguyen, Chunsheng Chen, Fuad Abdulla, Hao Nguyen, Tran Vo, Karina Bursch, Zachary M Kiser, Howard Levy, Leo E Otterbein, Gregory M Vercellotti
Journal: Blood (2017)
Five-Year Experience Using Bridging Radiotherapy Prior to Chimeric Antigen Receptor (CAR) T-Cell Therapies for B-Cell Malignancies at Memorial Sloan Kettering Cancer Center
Authors: Emily A. Silverman, Harper Hubbeling, M. Lia Palomba, N. Ari Wijetunga, Kathryn Tringale, Emily Lebow, Ana Alarcon Tomas, Roni Shouval, Connie Lee Batlevi, Renier J Brentjens, Parastoo B. Dahi, Sergio A Giralt, Richard J Lin, Jae H Park, Michael Scordo, Craig S. Sauter, Gunjan L. Shah, Miguel-Angel Perales, Carla Hajj, Joachim Yahalom, Brandon S. Imber
Journal: Blood (2021)
Abstract 13281: Idiopathic Ventricular Fibrillation Endophenotype Determines the Yield of Ultra-Rare <i>RYR2</i> Variants in Youthful Unexplained Sudden Cardiac Arrest
Authors: Marissa J Stutzman, David J Tester, Michael J Ackerman, John R Giudicessi
Journal: Circulation (2021)

Introduction: Loss-of-function variants in the RYR2-encoded cardiac calcium release channel underlie a small number of unexplained sudden cardiac arrest and death (SCA/SCD) cases. Objective: To determine if the yield of ultra-rare RYR2 variants in unexplained SCA patients with a default diagnosis of idiopathic ventricular fibrillation (IVF) depends on pre-defined IVF endophenotype and whether RYR2 variant-positive IVF cases have a discernible electrocardiographic phenotype. Methods: All SCA cases referred to Mayo Clinic’s Windland Smith Rice Genetic Heart Rhythm Clinic between 01/2000 and 04/2021 were reviewed. After exclusion of 116 cases where a probable SCA root cause was identified and/or RYR2 genetic testing was not pursued, a total of 64 unexplained SCA cases (36% female; 26 ± 11 years at the time of SCA) were included. Clinical data was extracted from the medical record and patients classified as having i) IVF (no diagnostic clues), N=38 (59%) ii) PVC-triggered ventricular fibrillation (PTVF; documented short coupled PVC-triggered ventricular arrhythmias), N=19 (30%), or iii) early repolarization syndrome (ERS; J-point elevation ≥0.1 mV in ≥2 contiguous leads, excluding leads V 1 -V 3 ), N=7 (11%). The yield of ultra-rare, non-synonymous RYR2 variants (MAF&lt;0.0001 in the Genome Aggregation Database) and electrocardiographic profiles were then compared. Results: Overall, a qualifying, ultra-rare RYR2 non-synonymous variant was identified in 5 out of 64 (7.8%) unexplained SCA patients. Of note, the yield of ultra-rare RYR2 missense variants was significantly higher in individuals with an PTVF endophenotype than those without [4/19 (21%) versus 1/45 (2.2%), p=0.02]. Interestingly, the majority of ultra-rare RYR2 variant-positive unexplained SCA survivors [3/5 (60%)] displayed an exercise stress test pattern characterized by the onset of ventricular ectopy at ~120 bpm with suppression at heart rates ≥140 bpm. Conclusions: The burden of ultra-rare RYR2 variants is higher in unexplained SCA patients with documented PTVF. Collectively, this data suggests that i) a subset of PTVF may have an underlying genetic basis and ii) some IVF- and PTVF-associated RYR2 variants may result in an identifiable electrocardiographic profile.
Abstract 10267: Thermogenic Modulation of Perivascular Adipose Tissue Ameliorates Cardioautonomic Deterioration in Prediabetes
Authors: Ibrahim AlZaim, Haneen Dwaib, Ghina Ajouz, Nahed Mougharbil, Marie-Elizabeth Ragi, Ali MROUEH, Marwan M Refaat, Omar Obeid, Ahmed El-Yazbi
Journal: Circulation (2021)

Introduction: Cardiac autonomic neuropathy, a risk factor of cardiovascular mortality, is a common manifestation of prediabetes. Evidence points to perivascular adipose tissue inflammation as a quintessential instigator of cardiovascular dysfunction in metabolic impairment. Interventions tailored to ameliorate such subtle cardiovascular involvement have not been forthcoming. Data emerging from our laboratory implicate alteration of adipocyte mitochondrial bioenergetics, particularly an upregulation of uncoupling protein 1 (UCP1) expression and subsequent augmentation of adipose tissue hypoxia, as a potential culprit driving localized adipose inflammation. Hypothesis: Inhibition of UCP1-mediated thermogenesis or activation of the alternative thermogenic pathway, futile creatine cycling, through supplementation with phosphate or creatine monohydrate, respectively, may ameliorate the inflammatory phenotype observed in non-obese prediabetic rats. Methods: A non-obese prediabetic rat model, developed in our laboratory was used. This phenotype is evoked by 12 weeks of hypercaloric feeding causing localized perivascular inflammation in absence of systemic markers of inflammation. Cardioautonomic function was assessed by invasive hemodynamics. Localized adipose tissue inflammation and macrophage polarization were examined. Results: UCP1 inhibition by phosphate supplementation reversed the blunted parasympathetic baroreflex sensitivity observed in prediabetic rats. This was associated with the alleviation of perivascular adipose tissue hypoxia, inflammation, and altered macrophage polarization. These changes were accompanied by normalization of metabolic efficiency that increased in prediabetic rats due to UCP1 upregulation. Similar functional effects were observed after creatine supplementation without changes in metabolic efficiency. Conclusions: Bypassing UCP1-mediated thermogenesis upregulated by increased caloric intake alleviates cardioautonomic deterioration triggered by perivascular inflammation. This is achieved by UCP1 inhibition with a potential risk of increased metabolic efficiency and weight gain, or by activation of the alternative thermogenic pathway of creatine cycling.
Abstract 9783: Fully Automated Evaluation of Left Ventricular Global Longitudinal Strain in Children: Aiming for a "Hands Off" Future in Functional Assessment
Authors: Hunter L Kauffman, Daisuke Matsubara, Michael Convery, Karen Miller, Michael Quartermain, Anirban N Banerjee
Journal: Circulation (2021)

Background: Global Longitudinal Strain (GLS) is a sensitive indicator of cardiac function in children. However, GLS analysis is limited by time-consuming manual tracing and interobserver variability. This study aims to assess clinical feasibility of AutoStrain, a “hands-off” method of GLS analysis in children. Hypothesis: AutoStrain will quickly and accurately calculate GLS in children. Methods: We prospectively enrolled 168 patients, who underwent clinically indicated echocardiograms (mean age:12±4 years). Strain parameters were measured using three methods: 1) Fully automated (AutoStrain, Phillips Medical Systems), 2) Semiautomated (manual correction of automated measurements), 3) Conventional manual measurements (2D-CPA, TomTec), from apical 4-, 3- and 2-chamber views. Automated analyses were timed with a stopwatch. Results: Fully automated measurements were feasible in all cases. The results are depicted in Table 1 and Figure 1. Fully automated AutoStrain showed a strong correlation with manual GLS (R=0.71, p&lt;0.001). Semiautomated AutoStrain showed a much stronger correlation with manual GLS (R=0.90, p&lt;0.001). In our cohort, 21% of patients required manual editing, mostly at the apex, at end-systole. Fully automated AutoStrain calculated GLS in 13±4s, while semiautomated AutoStrain required 73±53s (p&lt;0.001). Interobserver variability for fully automated measurements was zero. Bland Altman analysis revealed a small negative bias in fully automated analysis, indicating slight underestimation of GLS by AutoStrain (Figure 1). Conclusions: AutoStrain is a rapid, clinically feasible method for quantifying GLS in children. We speculate that accuracy of AutoStrain may improve in the future with inclusion of pediatric training datasets, as the anatomical intelligence program currently relies on adult datasets. Automated analysis may save time in busy laboratories, with the ultimate aim for a “hands off” future in functional assessment.
Abstract 9704: Mortality and Readmissions in Patients With Heart Failure With Preserved Ejection Fraction versus Heart Failure With Reduced Ejection Fraction
Authors: Yaser Carcora, Amy Gravely, Venkatakrishna N Tholakanahalli, Selcuk Adabag
Journal: Circulation (2021)

Introduction: Heart failure (HF) is a large public health problem with a 12 month mortality rate of 22% and a 30 day standardized readmission rate of 23%. We aimed to determine the differences in readmissions and long-term survival in patients with Heart Failure with Preserved Ejection Fraction (HFpEF) compared to Heart Failure with Reduced Ejection Fraction (HFrEF). Hypothesis: Heart Failure patients will have high mortality regardless of ejection fraction, with similar readmission rates across groups. Methods: We studied 3200 consecutive patients discharged from the hospital with a primary diagnosis of HF from October 2015 to March 2019. Patients were classified as HFpEF (EF &gt;50%) or HFrEF (EF&lt;50%). Results: At baseline, patients had a mean age of 75.0±10.3 and 97.9% were male. Patients with HFrEF were more likely to have coronary artery disease, myocardial infraction, diabetes, and more likely to be on beta blockers and ACE inhibitors (all p&lt;0.0001)(Table 1). Over 11.2±11.3 months of follow-up, patients with HFrEF were more likely to be readmitted (49.2 vs 37.5%, p&lt;0.0001)(Table 2). However, 3-year cumulative all cause death was no different between groups (34.6% vs. 34%; p=0.512) (Figure). Conclusions: Patients with HFrEF were more likely to have readmissions than those with HFpEF. But the long-term mortality was unacceptably high in both groups.
Prevalence and Disease Spectrum of Extracoronary Arterial Abnormalities in Spontaneous Coronary Artery Dissection
Authors: Alexandre Persu, Marilucy Lopez-Sublet, Abtehale Al-Hussaini, Marco Pappaccogli, Ibtissem Radhouani, Patricia Van der Niepen, William Adair, Christophe Beauloye, Pierre-Yves Brillet, Nathan Chan, Patrick Chenu, Hannes Devos, Javier Escaned, Marcos Garcia-Guimaraes, Frank Hammer, Robert Jackson, Salma Jebri, Deevia Kotecha, Fernando Macaya, Ciara Mahon, Nalin Natarajan, Kandiyil Neghal, Edward D. Nicol, Kelly S. Parke, Diluka Premawardhana, Averachan Sajitha, Joanne Wormleighton, Nilesh J. Samani, Gerry P. McCann, David Adlam
Journal: JAMA Cardiology (2021)

Spontaneous coronary artery dissection (SCAD) has been associated with fibromuscular dysplasia (FMD) and other extracoronary arterial abnormalities. However, the prevalence, severity, and clinical relevance of these abnormalities remain unclear.To assess the prevalence and spectrum of FMD and other extracoronary arterial abnormalities in patients with SCAD vs controls.This case series included 173 patients with angiographically confirmed SCAD enrolled between January 1, 2015, and December 31, 2019. Imaging of extracoronary arterial beds was performed by magnetic resonance angiography (MRA). Forty-one healthy individuals were recruited to serve as controls for blinded interpretation of MRA findings. Patients were recruited from the UK national SCAD registry, which enrolls throughout the UK by referral from the primary care physician or patient self-referral through an online portal. Participants attended the national SCAD referral center for assessment and MRA.Both patients with SCAD and healthy controls underwent head-to-pelvis MRA (median time between SCAD event and MRA, 1 [IQR, 1-3] year).The diagnosis of FMD, arterial dissections, and aneurysms was established according to the International FMD Consensus. Arterial tortuosity was assessed both qualitatively (presence or absence of an S curve) and quantitatively (number of curves ≥45%; tortuosity index).Of the 173 patients with SCAD, 167 were women (96.5%); mean (SD) age at diagnosis was 44.5 (7.9) years. The prevalence of FMD was 31.8% (55 patients); 16 patients (29.1% of patients with FMD) had involvement of multiple vascular beds. Thirteen patients (7.5%) had extracoronary aneurysms and 3 patients (1.7%) had dissections. The prevalence and degree of arterial tortuosity were similar in patients and controls. In 43 patients imaged with both computed tomographic angiography and MRA, the identification of clinically significant remote arteriopathies was similar. Over a median 5-year follow-up, there were 2 noncardiovascular-associated deaths and 35 recurrent myocardial infarctions, but there were no primary extracoronary vascular events.In this case series with blinded analysis of patients with SCAD, severe multivessel FMD, aneurysms, and dissections were infrequent. The findings of this study suggest that, although brain-to-pelvis imaging allows detection of remote arteriopathies that may require follow-up, extracoronary vascular events appear to be rare.
Abstract 9924: Polygenic Risk Score for PR Interval is Associated with Increased Risk of Ischemic Stroke
Authors: Huichun Xu, John W Cole, Brady Gaynor, Kathy Ryan, Braxton D Mitchell, Tatjana Rundek, Bradford B Worrall, Patrick T Ellinor, Diane Fatkin, Steven A Lubitz, Gui Pare, Dana Leifer
Journal: Circulation (2021)

Atrial cardiomyopathy (AC) is an emerging risk factor for ischemic stroke (IS). We used polygenic risk scores (PRS) to study the association of the PR interval (PRI)-- an ECG marker for AC-- with IS and IS subtypes. We studied PRI, rather than other AC traits, because a validated multi-ethnic PRI-PRS exists. Methods: We calculated PRI-PRS for patients in the NINDS Stroke Genetics Network (SiGN) database, which contains well-characterized stroke patients and in which we have found an association of a PRS for atrial fibrillation with IS subtypes. We derived PRS for 10 GWAS thresholds after a clumping procedure to eliminate SNPs in linkage disequilibrium. SNPs were weighted by their beta coefficients from the GWAS summary statistics to generate PRS. We normalized by the number of SNPs included. We used logistic regression to compare PRI-PRS in stroke cases (n=13930) and non-stroke controls (n=49473). We controlled for sex and the first 10 principal components of genetic ancestry. We stratified by genetic ancestry and genotype platforms. Logistic regression analyses for each stratum were meta-analyzed using an inverse-variance weighting-based method, assuming fixed effects. Results and Conclusions: In the overall meta-analysis, PRI-PRS was weakly associated with increased risk of IS (p&lt;0.02, only for one GWAS threshold). PRI-PRS was associated with increased risk of IS due to small artery occlusion (SAO) (p=0.032 and 0.033, using GWAS of PRI p-value thresholds 0.05 and 0.005 respectively), but not with other IS subtypes. The SAO association may reflect the association of PRI and hypertension, a risk factor for SAO. In a secondary analysis of European strata, we observed a robust association (p&lt;0.02 across all GWAS thresholds) of the PRI-PRS with all IS in GEOS, which consists of younger onset strokes (age of stroke onset &lt; 50 years). PRI-PRS was also associated in GEOS (p&lt;0.01 across all GWAS thresholds) with the subtype of strokes of undetermined origin, which includes embolic strokes of unknown source (ESUS). PRI-PRS was also associated with large artery strokes at some GWAS thresholds in GEOS. Our results suggest that genetic risk for prolonged PRI is associated with SAO and may have more robust associations with other stroke subtypes in some populations.
Abstract 14455: Outcomes and Revascularization Strategies for ST Elevation Myocardial Infarction in Patients With Hypertrophic Cardiomyopathy
Authors: Robert W Ariss, Abdul Minhas, SALIK NAZIR, Ayla Cash, Ali E Denktas, Hani Jneid
Journal: Circulation (2021)

Introduction: Myocardial ischemia is a well-known complication of hypertrophic cardiomyopathy (HCM). There are limited contemporary data on outcomes and revascularization strategies of STEMI outcomes in HCM. Methods: The National Inpatient Sample 2004-2018 was queried to identify adult patients presenting with a primary diagnosis of STEMI. Patients with STEMI and a concomitant diagnosis of HCM were subsequently identified. Complex samples multivariable logistic and linear regression models were used to determine the association of HCM with in-hospital outcomes (all-cause mortality, invasive mechanical ventilation, cardiogenic shock, mechanical circulatory support, and cardiac arrest). Outcomes of HCM patients with STEMI who were revascularized were also compared with their counterparts who were not revascularized. Results: Of 3,049,068 primary STEMI hospitalizations included within this study, 2,583 (0.8%) had an associated diagnosis of HCM. HCM patients were more likely to be elderly and female with less traditional cardiovascular risk factors compared to those without HCM. HCM patients were also less likely to receive percutaneous coronary intervention compared to those without HCM (42.8% 66.3% vs. P&lt;0.001). STEMI with HCM was associated with similar in-hospital mortality (adjusted odds ratio [aOR] 1.09; 95% confidence interval [CI] 0.82-1.44; P=0.561) and other outcomes compared to those without HCM (Table 1) . Notably, STEMI patients with HCM who were revascularized had similar in-hospital mortality (aOR 0.69; 95% CI 0.36-1.33; P=0.266) compared to their HCM counterparts who did not receive revascularization. Conclusions: Despite lower rates of revascularization, STEMI with HCM is associated with similar in-hospital mortality compared to those without HCM.