tbuckley/cabot-search huggingface dataset:
Abstract 12782: Serial Cerebral Hemodynamic Monitoring in Patients With HeartMate 3 Left Ventricular Assist Devices
Authors: Christopher G Favilla, Sarah Carter, Pavan Atluri, Navpreet Reehal, Michael Genuardi
Journal: Circulation (2023)

Introduction: Left ventricular assist device (LVAD) implantation improves cardiopulmonary hemodynamics and vital organ perfusion, but cerebral blood flow is not routinely measured despite the clinical significance of neurologic complications. We aimed to quantify the short and long-term impact of LVAD on cerebral hemodynamics by serially monitoring patients before and after LVAD implantation. Hypothesis: We hypothesize that LVAD implantation improves dynamic measures of cerebral blood flow: cerebral autoregulation (CA) and cerebrovascular reactivity (CVR). Methods: 20 patients with advanced heart failure with planned LVAD implantation participated in serial cerebral hemodynamic monitoring: (1) &lt;72-hours pre-implant, (2) &lt;72-hours post-implant, (3) 14-days post-implant, and (4) 90-days post-implant. Cerebral blood flow velocity was measured at each visit by transcranial Doppler. CA, quantified by Mx index , characterized the relationship between blood pressure and cerebral blood flow. CVR quantified the cerebral hemodynamic reserve, based on the response to a hypercapnic stimulus (5% inhaled CO 2 ). Results: As compared to the pre-implant assessment, no change was noted in absolute cerebral blood flow velocity ( Figure 1a ). However, CA improved immediately post-implant (0.47 vs 0.26; p=0.0007), at 14-days (0.47 vs 0.33; p=0.007), and at 90-days (0.47 vs 0.31; p=0.03), Figure 1b . Pre-implant CVR was not significantly altered at 14-days (1.14 vs 1.70, p=0.25) but improved at 90-days (1.14 vs 2.11, p=0.03), Figure 1c . Conclusions: Despite no change in cerebral blood flow velocity, LVAD implantation improves dynamic measures of cerebral blood flow, CA and CVR. Future studies should include longer follow-up and correlate post-LVAD cerebral hemodynamics with clinically meaningful neurologic endpoints such as stroke and cognitive decline.
Abstract 15077: Mitochondrial LonP1 Upregulation in End Stage Heart Failure
Authors: Saifullah Soliman, Ayman Maher M Ibrahim, Dr. Kerolos Wagdy, Peter Selwanos, Hadir Khedr, SABER MOSTAFA MOSTAFA, Ajay M Shah, Magdi Yacoub, Yasmine Aguib
Journal: Circulation (2023)

Introduction: Mitochondrial dysfunction is a hallmark of heart failure (HF), where correct mitochondrial proteins’ folding is challenged under mitochondrial stress. To restore mitochondrial proteostasis and homeostasis, the mitochondrial unfolded protein response (UPR mt ) is activated, a mechanism not fully elucidated in HF. Purpose: We here investigate the UPR mt induction in advanced/end-stage HF patients requiring Left Ventricular Assist Device (LVAD). In addition, we analyzed the potential influence on clinical outcome. Methods: RNA was extracted from 44 Left Ventricular discs excised during implantation of LVAD from end-stage HF patients and from 5 control LV tissues. Quantitative PCR was performed to assess the relative expression levels of UPR mt machinery ( ATF5, CHOP, mtDNAj, HSP60/10, CLpP and LonP1 ). Immunoblotting was performed to validate mRNA levels. LonP1 subgrouping was performed in reference to LVAD patients’ 3 rd quartile of pre-LVAD Lonp1 mRNA levels. The primary outcome for the Kaplan-Meier survival analysis was all-cause mortality post-LVAD intervention. Results: Gene expression analysis revealed a significant increase in mRNA levels of CHOP and LonP1. Immunoblotting validated the upregulation of CHOP &amp; LonP1 in end-stage HF tissue in comparison to controls. In High-LonP1 patients, we observed a significant increase in left ventricular ejection fraction and blood sodium levels while serum levels of ST-2 and blood urea levels were significantly decreased. High-LonP1 patients had a significantly higher probability of survival post-LVAD intervention and potential to recover myocardial function. Conclusion: This study suggests LonP1 as a potential marker of myocardial recovery and clinical outcome in end-stage heart failure patients treated by LVADs.
Abstract 18949: Bariatric Surgery is Associated With Improved Coronary Microvascular Function and Cardiorespiratory Fitness in Patients With Ischemia and Non-Obstructive Coronary Arteries (INOCA)
Authors: Ana Carolina do Amaral Henrique de Souza, Filipe A Moura, Sanjay Divakaran, Karla Sirianni, Eric G Sheu, Marcelo F Di Carli, Susan Redline, Ali Tavakkoli, Viviany R Taqueti
Journal: Circulation (2023)

Introduction - Severe obesity is associated with cardiometabolic disease and coronary microvascular dysfunction, as reflected by impaired coronary flow reserve (CFR). Bariatric surgery promotes sustained weight loss and lower incidence of diabetic microvascular complications, but its effect on the coronary microcirculation is unclear. In this ongoing pilot study, we aimed to investigate the impact of bariatric surgery on CFR, endothelial function, and cardiorespiratory fitness in patients with severe obesity and INOCA. Methods - Consecutive patients (N=19) with severe obesity (BMI≥35 kg/m 2 ), exertional dyspnea and planned bariatric surgery were enrolled. Patients underwent cardiac stress positron emission tomography (PET), peripheral arterial tonometry (PAT), echocardiogram and cardiopulmonary exercise testing (CPET) at baseline and after a median of 6.2 months post-surgery (N=9 completed to date). CFR was quantified as stress/rest myocardial blood flow (MBF) from PET. Reactive hyperemia index (RHI), a marker of endothelial function, was calculated as the ratio between PAT signal post and pre-occlusion in the corresponding arm. Results - Median age was 50 (Q1-Q3 42-54) years and 63% were female. At baseline, median BMI was 43 (40-54), LVEF was 0.62, and %LV visual ischemia was 0. Higher BMI inversely correlated with CFR (r= -0.53, p=0.02). As compared to baseline, patients post-surgery (78% sleeve gastrectomy, 22% gastric bypass) had significantly decreased BMI (45.2 vs. 34.3, p=0.008) and improved stress MBF [1.8 (1.3-2.2) vs. 2.4 (1.8-2.8), p&lt;0.02], CFR [2.3 (1.9-2.6) vs. 3.1 (2.4-3.6), p&lt;0.02] and peripheral endothelial function [RHI 1.5 (1.4-1.8) vs. 2.4 (1.8-2.8) vs. p=0.04]. These changes were accompanied on CPET by significantly higher exercise workload [112 (84.2-146) vs. 124.5 (90.5-149) W, p=0.046] and relative peak VO 2 [12.5 (11.9-14) vs. 15.2 (12.6-17) mL/kg/min, p=0.028]. Higher stress MBF directly correlated with relative peak VO 2 (r=0.53, p=0.04). Conclusion - In this pilot clinical study, bariatric surgery was associated with significant improvements in coronary microvascular function, peripheral endothelial function, and cardiorespiratory fitness in symptomatic patients with severe obesity after six months.
Abstract 14515: Distinct Genetic Mechanisms for Bradyarrhythmias From Multi-Center Multi-Ancestry Meta-Analyses
Authors: Lu-Chen C Weng, Joel Ramo, Sean J Jurgens, Mark Chaffin, Shaan Khurshid, Christopher M Haggerty, Kelly Cho, Aarno Palotie, Peter Wilson, Patrick T Ellinor, Steven A Lubitz
Journal: Circulation (2023)

Background: With an increasing prevalence in older adults, bradyarrhythmias pose a major public health problem. Hypothesis: Genetics can inform on disease pathophysiology and implicate targets for therapeutic development for bradyarrhythmias. Methods: We first performed ancestry-specific genome-wide association studies (GWAS) and combined the results in meta-analyses of up to 1.3 million individuals including 9,511 sinus node dysfunction (SND) cases, 34,086 distal conduction disease (DCD) cases, and 28,899 pacemaker implantation (PM) cases. We evaluated the biological relevance of bradyarrhythmia loci by analyses of transcriptomes, pleiotropy, and partitioned heritability based on cardiac single cell RNA sequencing data. Finally, we performed rare variant burden testing in 460,000 whole exome sequenced individuals (cases: 1,766 SND, 12,422 DCD &amp; 5,646 PM) from UK Biobank and Mass General Brigham Biobank. Results: Common variant analyses identified 13, 28, and 21 loci for SND, DCD, and PM, respectively. SND and DCD were moderately genetically correlated (r g = 0.64). Common variant loci included genes underlying familial forms of bradyarrhythmias (HCN4 and SCN5A) and genes regulating population-level variation in electrocardiographic traits. Four well-known common variant arrhythmia loci ( SCN5A / SCN10A , CCDC141 , TBX20 , and CAMK2D ) were shared for SND and DCD, while other loci were more specific for SND ( PITX2 , HCN4 , ZFHX3 ) or DCD ( CAV1 and NKX2 - 5 ). We observed an inverse association between predicted cardiac expression of SCN10A and risk of SND and DCD, and positive associations of predicted cardiac expression of CEP68 and STRN with risk of SND and DCD, respectively. Among 9 cardiac cell types, cardiomyocyte-expressed genes were enriched for contributions to DCD heritability. Rare variant analyses implicated LMNA for all bradyarrhythmia subtypes; SMAD6 and SCN5A for DCD; and TTN , MYBPC3 , and SCN5A for PM. Conclusions: We identify novel genes and loci associated with bradyarrhythmias. The genetic architectures of SND and DCD are both overlapping and distinct. Multiple genetic mechanisms involving ion channels, sarcomeric components, cellular homeostasis, and cardiac development may influence the development of bradyarrhythmias.
Abstract 16468: A Microtubule-Connexin 43 Regulatory Link Suppresses Cardiac Fibrosis and Arrhythmias in Duchenne Muscular Dystrophy Mice
Authors: Delong Zhou, Julie Nouet, Eric Himelman, Mauricio A Lillo Gallardo, Alexander Chong, Xander H Wehrens, George Rodney, Glenn I Fishman, Paul Lampe, Lai-Hua Xie, Natalia Shirokova, Jorge Contreras, Diego Fraidenraich
Journal: Circulation (2023)

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular degenerative disorder that leads to premature death in the teens because of multiple dysfunctions in the heart and skeletal muscle. DMD is caused by the absence of dystrophin, a sarcolemma protein encoded by the dmd gene, located on the X chromosome. 1:5,000 boys are diagnosed with DMD annually, and there is no cure. Clinically, steroid-based treatments reduce inflammation and thus, palliate skeletal muscle pathology. With improvements in the skeletal muscle, DMD-associated cardiomyopathy has become the leading cause of mortality because nearly all patients develop cardiac disease by age 20. Connexin 43 (Cx43) is a gap junction protein and is responsible for the electrical propagation of signals in the heart; it is upregulated and undergoes pathological remodeling, away from the intercalated disc in the heart of DMD mice (mdx) and patients. Hypo-phosphorylation of a specific triplet of serines in Cx43 had been found in mdx and DMD hearts. To study a potential rescue role for Cx43 phosphorylation in DMD, the triplet of serine residues was replaced by glutamic acid or alanine residues to create a phospho-mimic (Cx43-S3E) or a phospho-dead (Cx43-S3A) version of Cx43 respectively. We found that Cx43-S3E but not Cx43-S3A prevents Cx43 remodeling and development of fibrotic cardiomyopathy, arrhythmias, and heart failure in mdx mice. Remarkably, inhibition of hyperdensified, dystrophic microtubule (MT) polymerization by treatment with colchicine (Colch) enhances Cx43 phosphorylation and reduces Cx43 remodeling in dystrophic hearts, suggesting the presence of a MT-Cx43 regulatory connection. This connection could play an important role in the development of dystrophic cardiomyopathy. Our studies explore the electrophysiological properties of Cx43-S3E in DMD cardiomyocytes, and investigate a requirement for Cx43-S3A in the Colch-dependent improvement of the MT dynamics, uncovering a novel link between phospho-Cx43 and MT organization. Furthermore, the results suggest a novel target for the treatment of DMD-cardiomyopathy.
Abstract 13296: Cardiovascular Determinants of Exercise Capacity in Patients With Cancer
Authors: Ruben Evertz, Markus Anker, Christine Diehl, Friederike Braulke, Tobias R Overbeck, Tania Garfias-Veitl, Gerd P Hasenfuss, Andreas Schuster, Stephan von Haehling
Journal: Circulation (2023)

Introduction: Maintaining cancer patients′ exercise capacity and therefore patients′ self-determined life is of huge importance, but little is known about major determinants. We sought to identify determinants of exercise capacity in patients with a broad spectrum of cancer types, who were already receiving cancer treatment or about to commence such therapy. Methods: Exercise capacity was assessed in 253 consecutive patients mostly suffering from advanced cancer using the 6-minute walk test (6-MWT). All patients underwent echocardiography, physical examination, resting electrocardiogram (ECG), hand grip strength (HGS) measurement, and laboratory assessments. Results: Patients were divided into two groups according to the median distance in the 6-MWT (459 meters). Patients with lower exercise capacity were older, had significantly lower HGS and haemoglobin and higher values of high sensitive (hs) Troponin T and NT-proBNP (all p &lt;0.05). Whilst the co-morbidity burden was significantly higher in this group, no differences were detected for sex, body mass index, tumour type, or cachexia (all p &gt; 0.2). Using multivariable logistic regression, we found that the presence of anaemia (odds ratio (OR) 6.172, 95% confidence interval (CI) 1.401-27.201, p=0.016) as well as an increase in hs Troponin T (OR 3.077, 95% CI 1.202-5.301, p=0.019) remained independent predictors of impaired exercise capacity. Increasing HGS was associated with a reduced risk of a lower exercise capacity (OR 0.896, 95% CI 0.813 - 0.987, p=0.026). Conclusions: Screening patients for elevated hs troponin levels as well as reduced HGS may help to identify patients at risk of lower exercise capacity during cancer treatment.
Abstract 13466: Trends in Prevalence of Psychiatric Cardiovascular Risk Factors for Women Veterans
Authors: Ramin Ebrahimi, Jennifer Sumner, Aaron Perkins, paul dennis, jean beckham, A. Laurie Shroyer, Carlos Alvarez
Journal: Circulation (2023)

Introduction: Psychiatric disorders such as anxiety, depression, and posttraumatic stress disorder (PTSD) have been increasingly recognized as cardiovascular disease (CVD) risk factors in the past two decades. US women Veterans (WV) are a growing and high-risk population for CVD. The goal of this study was to investigate the prevalence of these psychiatric CVD risk factors among US WV over a two-decade period. Methods: The national Veterans Affairs electronic health records were utilized to assess prevalence of the above disorders among US WV who visited a VA facility from 1/1/2000 to 12/31/2019. All diagnoses were based on International Classification of Disease (ICD) 9 th and 10 th version diagnostic codes. Results: Over the study period, the population of WV grew from 80,707 to 739,309, and the average age of the WV remained stable, 48 (2000) and 49 (2019) years old. Table 1 reveals the prevalence of these psychiatric CVD risk factors over the study period. Prevalence of each psychiatric disorder increased over the study period, with accelerated growth over the last decade of the study period. Conclusion: The prevalence and growth of these psychiatric l CVD risk factors among US WV is alarming. Focused research is warranted on potential interventions to reduce, and treat these nontraditional CVD risk factors to improve both psychiatric and cardiovascular health for WV.
Abstract 18787: Rural Intervention for Caregivers’ Heart Health: A Randomized Controlled Trial
Authors: Debra K Moser, JungHee Kang, MinKyoung Song, Misook L Chung
Journal: Circulation (2023)

Background: Informal caregivers are at greater risk for cardiovascular disease (CVD) than non-caregivers. This risk is higher for older caregivers who often have chronic illnesses, especially those living in a rural environment. Yet caregivers, particularly rural caregivers, are usually “hidden patients” in a caregiver-patient dyad as they commonly ignore their own health. We developed a CVD-risk reduction intervention (RICHH) that promoted self-care in the context of the demands of caregiving. Our aims were to test the impact of RICHH on adherence to CVD risk reduction behaviors and to determine whether age moderated intervention effects on outcomes. Methods: Rural informal caregivers (N=311; 76% female, age=55±14 years) at CVD risk were randomized to intervention or usual care groups. The intervention group completed a 12-week self-care intervention using video conferencing. Outcomes were assessed at 4 and 12 months. Adherence to CVD risk reduction behaviors and adherence to healthy diet was assessed using the Medical Outcome Scale-CVD Specific Adherence Scale and the Healthy Eating Index-2015 (HEI). Piecewise linear mixed-effect modeling determined intervention effects and age moderation. Results: Compared to the usual care group, adherence to CVD risk reduction behaviors increased in intervention at 4 months (b = 2.02, p &lt; 0.001), and the improvement was maintained at 12 months (b = 4.17, p &lt; 0.001; Figure). Total diet quality was improved in intervention versus control at 4-months (b = 0.95, p &lt; 0.001) and was maintained at 12 months (b = 3.05, p = 0.024). Consumption of fruits, vegetables, and whole grains increased in intervention, while intake of sugar and saturated fats decreased. Age did not moderate intervention effects. Conclusion: The intervention was effective in improving adherence to CVD risk reduction behaviors, including heart-healthy eating, regardless of caregiver age, showing its effectiveness for all ages of caregivers.
Abstract 15582: Robotic-Assisted versus Conventional Mitral Valve Repair: An Updated Meta-Analysis of Operative and Post-Operative Outcomes
Authors: Muhammed K Elfaituri, Ala Khaled, Ahmed BenGhatnsh, Taha Khaled, Hazem Abdelkarem A Faraj, Ahmed Msherghi
Journal: Circulation (2023)

Introduction: Cardiac surgery has seen notable advancements, especially in mitral valve repair, with the emergence of robotic-assisted mitral valve repair (RAMVR). Amid ongoing debates about RAMVR's efficacy and safety versus conventional mitral valve repair (CMVR), this updated meta-analysis offers a comprehensive comparison based on recently published data. Aim: The study aims to provide a comparison of RAMVR and CMVR, focusing on key operative and postoperative outcomes. Methods: A systematic search was conducted utilizing databases such as PubMed, EMBASE, and the Cochrane Library, until January 2023. The inclusion criteria included studies that compared RAMVR with CMVR. The meta-analysis incorporated a random-effects model to calculate pooled mean differences (MD) and relative risks (RR). All statistical analyses were carried out using R software (version 4.0.3), by metafor and meta packages. Results: Ten studies with a total of 54,235 patients (5,092 in the RAMVR group and 49,143 in the CMVR group) were included. The meta-analysis showed that RAMVR was associated with a significantly shorter hospital stay (MD -1.79 days; 95% CI -2.77 to -0.83, P=&lt;0.01, I2=100%) and ICU length of stay (MD -16.76 days; 95% CI -29.34 to -4.19, P=&lt;0.01, I2=98%). However, RAMVR was associated with significantly longer cardiopulmonary bypass time (MD 42.90 minutes; 95% CI 29.58 to 56.22, P&lt;0.01, I2=98%) and cross-clamp time (MD 29.67 minutes; 95% CI 19.84 to 39.51, P&lt;0.01, I2=98%). In terms of relative risks, RAMVR had a lower rate of overall mortality (RR 0.55; 95% CI 0.42 to 0.74, P&lt;0.01, I2=0%) and rate of infection (RR 0.62; 95% CI 0.52 to 0.74, P&lt;0.01, I2=0%). However, there was no statistically significant difference in the rate of blood transfusion, stroke rate, atrial fibrillation, and transient ischemic attack. Conclusions: This study suggests that RAMVR may offer benefits such as shorter hospital and ICU stays and lower overall mortality and infection rates, but it also involves longer cardiopulmonary bypass and cross-clamp times. Given the high heterogeneity across the included studies, this underlines the importance of further high-quality randomized controlled trials to optimize RAMVR techniques for improving patient outcomes in mitral valve repair.
Abstract 15969: Temporal Trends and Cardiovascular Outcomes in Hospitalized Patients With Fabry Disease: Insights From the National Inpatient Sample
Authors: Darren Kong, James Choi, Sara Diaz Saravia, Bejamin Adegbite, Errol C Moras, Kiran Mahmood
Journal: Circulation (2023)

Introduction: Fabry disease, a lysosomal storage disease consisting of an alpha-galactosidase-A deficiency, is associated with multi-organ disease including the liver, kidneys, and heart. New enzyme replacement and gene therapies have emerged in recent years to treat Fabry disease. Hypothesis: We aim to study temporal trends and cardiovascular outcomes in hospitalized patients with Fabry disease. Methods: Using the National Inpatient Sample (NIS) database we collected major adverse cardiovascular events (MACE) including arrhythmias, acute myocardial injury, stroke, cardiac arrest, and heart failure that occurred each year from 2017-2019. Appropriate ICD-10 codes were used for data collection. Proportions were calculated and adjusted odds ratios OR were determined using the Charlson Comorbidity Index. Results: Overall, there was an increase in total hospitalizations in patients with Fabry disease from 2017 to 2019. Fabry disease was associated with increased risk of MACE (OR=2.88, CI 1.99-3.68, P&lt;0.000) when compared with patients without Fabry disease. There was a significantly higher proportion of MACE in Fabry disease when compared to the general population from 2017-2019 (P-trend &lt;0.000). Secondary outcomes showed a increased risk of arrhythmias (OR=4.89, CI 3.22-7.08, P&lt;0.000) and heart failure (OR=4.34, CI 2.90-6.50, P&lt;0.000), but no significantly increased risk of acute myocardial injury (OR=3.11, CI 0.96-4.62, P=0.07) or stroke (OR=1.79, CI 0.76-2.41, P=0.11). Conclusions: Fabry disease is associated with worse inpatient cardiovascular outcomes when compared to patients without Fabry disease. Tissue injury from infiltrative deposits may cause subsequent myocardial fibrosis and conduction diseases, leading to heart failure and conduction diseases, respectively.