tbuckley/cabot-search huggingface dataset:
Abstract 18669: Pheochromocytoma Crisis Precipitated by Carvedilol
Authors: Zachary Walder, Michelle Stefanelli, Jetmir Vojnika
Journal: Circulation (2023)

Description of case: Pheochromocytomas are rare, catecholamine-secreting tumors of the adrenal gland. Definitive treatment is surgical, but requires pre-operative optimization with alpha, followed by beta blockade (BB). Initial treatment with BB can precipitate pheochromocytoma crisis, characterized by hemodynamic instability and end-organ dysfunction. This case describes pheochromocytoma crisis in a young, healthy female after switching from metoprolol to carvedilol. A 27-year-old woman is evaluated by an outpatient cardiologist for recurrent palpitations, “hot flashes” and headaches. Mobile telemetry monitor reveals episodes of “SVT” for which she is started on metoprolol succinate. Given her symptoms, testing for plasma free metanephrines is ordered and is markedly abnormal. Subsequently the patient is switched from metoprolol to carvedilol. Within a few hours of taking carvedilol the patient reports sudden onset dyspnea, nausea, vomiting and chest pain. On arrival, vital signs are remarkable for a resting pulse of 130 and blood pressure of 130/97. EKG shows sinus tachycardia. Labs reveal a high-sensitivity troponin of 1,816 ng/L and a 2-hour troponin of 4,560. CT shows a 5.8 cm left adrenal mass. An echocardiogram reveals a reduced LVEF of 45-50% and is suggestive of reverse takotsubo cardiomyopathy. Her carvedilol is discontinued, she is started on prazosin and her symptoms resolve within 24 hours. She later resumes metoprolol and proceeds with surgical excision. Discussion: This case reports a pheochromocytoma crisis likely precipitated by carvedilol and complicated by reverse-takotsubo cardiomyopathy. Interestingly, the patient tolerated metoprolol despite being in the same class. This switch was made knowing she tolerated BB and with the idea that she would benefit from additional alpha-blockade. Carvedilol is a racemic mixture, with S-carvedilol binding beta-1 and -2 receptors while R-carvedilol binds strictly alpha-1. There is evidence that patients catabolize the enantiomers differentially, resulting in higher concentrations of one enantiomer in an unpredictable manner. It is therefore preferred to avoid all BB before sustained alpha blockade while treating pheochromocytoma despite the patient’s previous tolerance.
Abstract 18558: Modeling Cardiac Amyloidosis: Insights Into Pathogenesis and Therapeutic Strategies
Authors: Shany Glatstein, Gil Arbel, Irit Huber, yehuda wexler, Matteo Ghiringhelli, Lior Gepstein
Journal: Circulation (2023)

Introduction: Cardiac transthyretin (TTR) amyloidosis is an underdiagnosed cause of heart failure and cardiac arrhythmias. The lack of relevant human cardiac tissue models hinders understanding of the underlying mechanisms and development of effective treatments. Hypothesis: We aimed to establish an in vitro model of cardiac amyloidosis using human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) and aggregated TTR and investigate cellular changes and potential therapeutic targets. Methods: Wild-type and mutated TTR proteins were aggregated and added to hiPSC-CM cultures directly or embedded in Matrigel used for culture-plate coating. Single-cell and two- and three-dimensional hiPSC-CM models were used for real-time microscopy, calcium and voltage imaging, immunostaining, apoptosis, ROS assays, and proteomics studies with mass spectrometry. Results: Immunohistochemical and histological staining confirmed the deposition of TTR aggregates within the hiPSC-CM tissue models. Cells exposed to TTR aggregates exhibited increased apoptosis and increased production of reactive oxygen species (ROS). TTR-treated cells also displayed irregular calcium transients, characterized by oscillating calcium peaks and double-humped signals. The presence of TTR also induced morphological changes, including cell shrinkage at the single-cell level and the formation of holes in 2D hiPSC-CM cell sheets due to cell migration and apoptosis. These holes led to conduction abnormalities and the development of reentrant arrhythmias, specifically spiral waves. The severity of these abnormalities was markedly increased when mutant TTR aggregates were used. Proteomics studies suggest a potential involvement of the mTOR signaling pathway in the pathogenesis of cardiac amyloidosis. Conclusions: Our in vitro model successfully recapitulated key features of cardiac amyloidosis and revealed significant protein expression changes. These findings provide valuable insights into disease pathogenesis and potential therapeutic targets and highlight the utility of our model for studying cardiac amyloidosis for the development and evaluation of novel therapeutic strategies.
Abstract 11600: Association Between Obesity and Risk of Total and Obesity-Related Cancer in Persons With Incident Cardiovascular Disease
Authors: Sarah Malik, Avirup Guha, Xiaoling Wang, Neal L Weintraub, Ryan A Harris, Biplab Datta, Justin Moore, Priyanshu Nain, Sagar Patel, Steven Coughlin, Elizabeth Polter, Anna Prizment, Anne Blaes, Roberta Florido, Shelby Kutty, Alvaro Alonso, Corinne Joshu, Elizabeth Platz
Journal: Circulation (2023)

Introduction: Cardiovascular disease (CVD) and cancer often occur in the same people, in part due to shared risk factors. In a Global Burden of Disease analysis of cohorts from &gt;180 countries, obesity was a top 3 modifiable risk factor for CVD and cancer. Beyond shared risk factors, CVD pathophysiologies may synergize with obesity to influence carcinogenesis. If so, an excess cancer risk in obese persons with CVD has implications for clinical management. Hypothesis: Obesity is positively associated with obesity-related cancer (ObCa) risk in persons with incident CVD independent of shared risk factors. Methods: We used data from the Atherosclerosis Risk in Communities (ARIC) study, a cohort with 28 years of cancer follow-up. The analytic cohort was 5127 participants with incident CVD among whom 1511 were diagnosed with a first primary cancer. Follow up began at incident CVD diagnosis date after visit 1. Obesity was classified by BMI, waist circumference (WC), and waist-to-hip ratio (WHR) measured by trained technicians. We calculated incidence rate differences (RD) between obesity groups adjusted for age, sex, and center. The obesity-cancer association was estimated using Fine-Gray regression adjusted for shared risk factors, including smoking. Results: In people with CVD, cancer incidence was higher in the obese (BMI: RD=226.6/100,000 person-years) than normal weight group. In people with CVD, obesity was suggestively positively associated with ObCa (Table 1). In females with CVD, obesity was associated with increased ObCa risk. Associations were null in males, including after excluding prostate cancer. Conclusion: In this prospective study, obesity is positively associated with ObCa risk in women with incident CVD independent of shared risk factors. More work is needed to investigate why the association appeared in women only, and to identify possible mechanisms by which CVD pathophysiologies may interact with obesity to produce cancer risk.
Abstract 15864: Genetic Findings of Cardiac Sarcoidosis in a Case of Apical Variant Hypertrophic Cardiomyopathy With Recurrent Ventricular Tachyarrhythmias
Authors: Jeffrey Ding, PATRICK AZCARATE, Jason M Duran, Angel Soto-Hermida, Paul Bushway, Richard Ainsworth, Wei Wang, Jingjing Hu, Eric Adler
Journal: Circulation (2023)

Background: Genetic sequencing is changing the way physicians practice medicine. Hypertrophic cardiomyopathy (HCM) is one of the most common inheritable cardiac diseases. Sarcoidosis is a multisystem disease involving granulomatous infiltration of the lungs, heart, and other organs thought to be caused by a dysregulated immune system, influenced by genetic factors. Here, we present a case where an individual initially diagnosed with HCM was experiencing frequent episodes of ventricular tachycardia (VT). Further workup, including advanced imaging along with whole genome screening (WGS), revealed an unlikely diagnosis of concurrent cardiac sarcoidosis (CS). Clinical History: A 62-year-old man had ventricular fibrillation with workup notable for an ECG with deeply inverted T-waves, normal coronary angiography, and an echocardiogram and MRI showing apical HCM. An ICD was placed. Six years later, he had VT requiring a shock and was started on sotalol. He has now developed recurrent exercise-induced VT. While VT is seen HCM, the increasing frequency prompted further evaluation. A CT coronary angiogram showed normal coronaries and mediastinal lymphadenopathy. Lymph node biopsy revealed noncaseating granulomas and a PET/CT revealed hypermetabolic basal myocardium meeting HRS criteria for CS. Given minimal apical FDG uptake and a low likelihood that he had CS for 9 years without significant fibrosis, he likely has both HCM and CS. Using WGS, four genetic variants previously described in CS and HCM were identified confirming this diagnosis, HLA-DRB1, HLA-DQA1, ALPK3, and TTN. Discussion: HLA-DRB1 and HLA-DQA1 are both major histocompatibility complexes associated with CS. ALPK3 encodes alpha kinase 3 while TTN encodes titin. Truncating variants of ALPK3 are associated with HCM while pathogenic TTN variants have been described to cause HCM, DCM, and ARVC. This case reflects the potential of WGS in aiding clinicians in confirming an unlikely diagnosis.
Abstract 14699: Effects of Papillary Muscle Approximation and Annuloplasty Ring Sizing for Functional Mitral Regurgitation Repair in Enlarged Ventricles
Authors: Gediminas Gaidulis, Lakshmi Dasi, Muralidhar Padala
Journal: Circulation (2023)

Introduction: Our recent large animal study showed that papillary muscle approximation (PMA) repairs functional mitral regurgitation (FMR) and increases valve coaptation in enlarged left ventricles without negatively affecting ventricular function. However, since PMA does not reduce mitral annular dilation, addition of annuloplasty ring might be beneficial for such repair. In this study, we used computational modeling to investigate the benefit of the addition of annuloplasty to PMA and the effects of ring sizing on FMR repair in enlarged ventricles. Methods: 3D echo images were obtained in 3 pigs with heart failure, enlarged ventricles, and FMR. Each echo dataset was segmented, and computational model of the mitral valve was developed. To mimic PMA repair, the papillary muscles were drawn together in diastole. A true-sized annuloplasty ring of 40 mm and two downsized-rings of 38 mm and 36 mm were then added to each model. Leaflet closure was simulated and mitral valve geometry and biomechanics in peak systole were evaluated ( Fig A-B ). Results: On average, compared to pre-repair, PMA increased coaptation area by 30.6%, while the addition of annuloplasty increased this area by 85.1% with 40 mm, 138.1% with 38 mm, and 190.6% with 36 mm ring. Tenting area was reduced by 45.8% after PMA, 64.1% with the addition of 40 mm ring, 70.6% with 38 mm, and 76.5% with 36 mm ring. PMA reduced tension forces in chordae by 19.8%, while adding true-sized ring reduced forces by 16.4%. Annular downsizing allowed to reduce chordal forces by 31.2% with 38 mm, and 43.0% with 36 mm ring. Peak leaflet stress was observed on the P2 cusp, and PMA reduced it by 26.9%. True-sized ring reduced peak stress by only 10.7%, while 38 mm ring by 29.9%, and 36 mm by 43.7% ( Fig C ). Conclusions: Addition of true-sized ring to PMA further improved systolic valve geometry but not biomechanical parameters. Annular downsizing added to PMA was more beneficial for FMR repair, as it improved both mitral valve geometry and biomechanics.
Abstract 16776: Recurrent Admission of Acute Decompensated Heart Failure Among Patients With and Without PAD and Its Significance in the CKD Population: The ARIC Cohort Study
Authors: Zainali S Chunawala, Deepak L Bhatt, Arman Qamar, Muthiah Vaduganathan, Robert J Mentz, Kunihiro Matsushita, Justin L Grodin, Ambarish Pandey, Melissa C Caughey
Journal: Circulation (2023)

Introduction: Peripheral artery disease (PAD) and chronic kidney disease (CKD) are common comorbidities in patients with heart failure (HF). Importantly, CKD is associated with a greater risk of incident PAD and is a known risk factor for worse outcomes in HF patients. However, it is unclear whether the concomitant existence of PAD and CKD increases the risk of recurrent hospitalization for acute decompensated heart failure (ADHF). Methods: Since 2005, the Atherosclerosis Risk in Communities (ARIC) study has conducted hospital surveillance of ADHF with events verified by physician review. Demographics, comorbidities, laboratory data, and medications were abstracted from medical record by trained personnel. Hazard ratios of ADHF readmissions were analyzed using repeat-events Cox regression. Models were adjusted for age, race, sex, year and hospital of admission, coronary artery disease (CAD), COPD, and diabetes mellitus. CKD was defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73m 2 . Results: From 2005-2018, there were 1049 index hospitalizations for ADHF (mean age 77 years, 66% white) with measured creatinine, who were discharged alive. Of these, 155 (15%) had a diagnosis of PAD and 66% had CKD stage 3a or worse (GFR ≤60 mL/min/1.73m 2 ). Patients with PAD had a greater prevalence of smoking, CAD, myocardial infarction, and stroke. The 1-year ADHF readmission rate tended to be higher in patients with PAD, irrespective of CKD stage, compared to those without PAD ( Figure 1 ). After adjustments, PAD was associated with greater hazards of 1-year ADHF readmissions, both in patients with CKD stage 3a or worse (HR, 1.71; 95% CI: 1.25 - 2.32) and without CKD (HR, 1.84; 95% CI: 1.07-3.15). Conclusion: Patients with ADHF and concomitant PAD have a higher prevalence of cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of the CKD status. Focused strategies to prevent ADHF readmission in this high-risk group are warranted.
Abstract 17635: Proteomic Signatures of Diabetes-Related Coronary Heart Disease: The Atherosclerosis Risk in Communities Study
Authors: Justin B Echouffo, Bige Ozkan, Jingsha Chen, Mary R Rooney, Ron C Hoogeveen, Kuni Matsushita, Christie M Ballantyne, Elizabeth Selvin, Josef Coresh, Chiadi E Ndumele
Journal: Circulation (2023)

Introduction: The proteomic alterations that characterize coronary heart disease (CHD) in patients with type 2 diabetes are largely uncharacterized. Hypothesis: There are unique proteomic signatures of diabetes-related CHD. Methods: We quantified 4,955 plasma proteins using an aptamer-based assay (SomaLogic v4.0) in Atherosclerosis Risk in Communities (ARIC) Visit 2 (1990-92) participants. Incident CHD as defined as either myocardial infarction or fatal CHD. We used Cox regression to estimate the hazard ratios for the proteins and CHD associations, stratified by baseline diabetes status. We used Bonferroni-corrected p -values to adjust for multiple comparisons. Results: We included 9,939 individuals free of CHD (mean age: 57±5.7 years, 58% women, 23% Black adults, 14 % with diabetes). Over a median 25 years follow-up, there were 1,281 CHD events (330 among individuals with diabetes). Among 1,426 individuals with diabetes, after adjustment for confounders, 21 proteins were associated with incident CHD (p&lt;10 -5 ) (Figure, Panel A). Of these proteins, 16 were also associated with prevalent diabetes and 11 exhibited a significant interaction by diabetes status (p&lt;0.05/21 - Figure, Panel B). The top 6 proteins uniquely associated with diabetes-related CHD include inactive tyrosine-protein kinase 7, semaphorin-4D, scavenger receptor class A member 5, kremen protein 1, and cartilage intermediate layer protein 2, and semaphorin-6A. Among those without diabetes, of the 8 proteins significantly associated with CHD (p&lt;10 -5 ), growth differentiation factor-15 was the only one that overlapped with proteins identified among individuals with diabetes. Conclusions: A large-scale proteomics analysis identified 20 novel proteomic markers unique to diabetes-related CHD. Our findings have the potential to shed more light on biological pathways linking diabetes and CHD.
Abstract 16805: A Mental Health Curriculum for Pediatric Cardiology Fellows: Increasing Preparedness of Pediatric Cardiologists to Meet the Needs of Patients at Increased Risk
Authors: Amanda D McCormick, Sonal T Owens, Heang M Lim, Carolyn Vitale, Melissa K Cousino
Journal: Circulation (2023)

Introduction: Mental health (MH) is an important yet understudied area of care for patients with congenital heart disease (CHD). It is known that children and adults with CHD have increased incidence of MH disorders when compared to their peers. MH disorders are not reliably identified in the pediatrics population at large, and many children who would benefit from treatment of MH conditions do not receive appropriate care. Pediatric subspecialty fellows feel MH should be within their scope, but few feel competent in their ability to appropriately screen and make treatment referrals. Research Question: Does a didactic-based MH curriculum improve the preparedness of pediatric cardiology fellows to identify and refer patients at need for MH care? Aims: Determine the comfort of pediatric cardiology fellows with MH knowledge, screening, and treatment recommendations, before and after a didactic- based curriculum. Methods: A 9 session didactic based curriculum was designed by a multi-disciplinary team of experts, administered over 9 months (September 2021 - June 2022 and September 2022 - June 2023). Topics included MH and CHD Overview, MH Screening and Clinic-Based Interventions, Psychopharmacology, Delirium, Substance Abuse, Trauma-Informed Care, and Adult CHD and Transitional Care. An investigator designed survey was developed to assess fellow comfort with MH knowledge, screening, and treatment recommendation domains, and was administered at the beginning and end of the curriculum in each academic year. Results: 24 fellows participated over 2 academic years, 14 completed the pre-post survey (11/17 in year 1, 3/6 in year 2). Most participants were in their first year of training (9/14, 57%). Overall, fellow comfort with MH topics increased significantly (mean score 2.89±0.46 vs. 3.4±0.4, p = 0.0005), with improved comfort in the MH knowledge and treatment recommendation domains (p = 0.003 and p = 0.001). Conclusion: A didactic based MH curriculum improves the comfort and preparedness of pediatric cardiology fellows to address MH concerns of their patients. This curriculum will continue to be refined in topics over time but could be generalized to training programs nationally and across pediatric specialties to improve MH care for high-risk patients.
Abstract 13006: Telemedicine Disparities in Ambulatory Cardiology Patients in a Large Academic Health System
Authors: Lochan M Shah, Colin Wu, Sean Tackett, Lily Sadauskas, Helen Hughes, Nisha A Gilotra
Journal: Circulation (2023)

Introduction: Although the COVID-19 pandemic prompted rapid expansion of telemedicine, the effect of system-wide digital health strategies on vulnerable populations remains to be understood. Given video visits offer several advantages over audio-only visits, telemedicine encounters are typically preferentially scheduled as video visits; however, access complexities may lead to audio-only encounters and exacerbate the digital divide. Aim: We aimed to identify sociodemographic characteristics associated with telemedicine visit modality in the outpatient cardiology population in a large academic health center. Methods: We assessed all outpatient cardiology telemedicine visits from 1/1/2020-12/31/2021 via the Johns Hopkins Telemedicine Equity Dashboard, which sources its data from the electronic medical record. Our primary outcome was visit modality, with an adverse outcome defined as video-to-audio visit conversion. The first telemedicine encounter for each unique patient was included (accounting for 85% of all telemedicine encounters during study period). We assessed predictors of video-to-audio visit conversion using simple and multivariate logistic regression with relevant pre-determined sociodemographic variables (see Figure ). Results: There were 47,961 total telemedicine encounters, spread between 39,381 unique patients. Odds of conversion from video to audio-only visit increased with age, with the highest odds of conversion to audio-only visit in patients age 75+. Non-White race, Medicaid, Medicare and self-pay insurance status, and higher social deprivation index (SDI) quintile were also associated with increased odds of audio-only modality. Conclusion: Current telemedicine strategies would benefit from further analysis and targeted intervention to develop a more equitable digital care delivery system, particularly for patients that are older, non-White, do not have private insurance, and live in areas with higher SDI.
Abstract 12820: The Use of Mineralocorticoid Receptor Antagonists but Not Renin-Angiotensin System Inhibitors is Associated With Better Outcomes in Patients With Heart Failure and Advanced Chronic Kidney Disease
Authors: Nobuyuki Enzan, Shouji Matsushima, Hidetaka Kaku, Takeshi Tohyama, Takuya Nagata, Tomomi Ide, Hiroyuki Tsutsui
Journal: Circulation (2023)

Introduction: The usefulness of mineralocorticoid receptor antagonists (MRA) or renin-angiotensin system (RAS) inhibitors in patients with heart failure and advanced chronic kidney disease (CKD) remains to be established. This study sought to determine whether MRA or RAS inhibitors could improve outcomes in HF and CKD patients. Methods: We analyzed HF patients enrolled in the Japanese Registry Of Acute Decompensated Heart Failure (JROADHF), a national database of HF. The primary outcome was composite of cardiovascular death or cardiovascular rehospitalization. In overall cohort, we used cubic spline analysis adjusted for potassium levels and other covariate to elucidate effects of MRA or RAS inhibitors on outcomes as a function of creatinine clearance. Next, we conducted propensity score matching within patients with creatinine clearance &amp;lt; 30 ml/min/m 2 . Results: Out of 9,637 eligible patients, 4,774/6,428 patients received MRA/RAS inhibitors, respectively. Cubic spline analysis showed that both MRA and RAS inhibitors were associated with better primary outcomes in patients with lower left ventricular ejection fraction, which was consistent with previous studies. It means that our dataset was concordant with other registries. MRA was associated with better outcomes in patients with lower creatinine clearance, and not in patients with higher creatinine clearance (Figure). Conversely, RAS inhibitors was associated with better outcomes only in patients with higher creatinine clearance. Among patients with creatinine clearance &amp;lt; 30 ml/min/m 2 , propensity score matching yielded 610 pairs. In these pairs, MRA was associated with lower incidence of cardiovascular events (399 vs. 486 incidence per 1,000 person-years; incidence rate ratio 0.821 [0.714-0.944]; P = 0.006). Conclusions: The use of MRA, not RAS inhibitors, was associated with better outcomes in patients with heart failure and advanced chronic kidney disease.