tbuckley/cabot-search huggingface dataset:
Abstract 4138690: A Case of Hypertrophic Cardimyopathy: Digenic Variants of Uncertain Significance Mutations in MHY7 and RYR2 Genes
Authors: Selina Durukan, Ekin Uzunoglu, Maryam Farahmandsadr, Daniel Soffer
Journal: Circulation (2024)

Introduction: Hypertrophic Cardiomyopathy (HCM) is primarily a disease caused by mutations in single genes, but around 5% of HCM patients, exhibit 2 (digenic) or more (oligogenic) causal mutations in the same gene or in different genes. We present a case of familial HCM with variants of uncertain significance (VUS) mutations in the MYH7 and RYR2 genes, highlighting the complexity of genetic inheritance and its implications on disease severity. Case presentation: A 40-year-old male presented with a history of hypertension, HCM, and two prior myocardial infarctions. He had syncope, non-sustained ventricular tachycardia, and a family history of sudden cardiac death (SCD) in his maternal grandfather. A dual-chamber ICD was placed for primary prevention of SCD because of his high-risk profile. Echocardiography demonstrated normal LV size and function with moderate asymmetric septal hypertrophy. Cardiac MRI indicated diffuse asymmetric hypertrophy and a 10.9% LV myocardial scar burden. Left heart catheterization revealed normal coronary arteries with LVOT gradient up to 60 mmHg, consistent with HCM. Genetic testing revealed VUS in the MYH7 (c.1305G&gt;A, p.Met435Ile) and RYR2 (c.10528C&gt;A, p.Arg3510Ser) genes (Figure 1). Further family genetic testing confirmed these VUS mutations in multiple relatives (Figure 2). Discussion: The identification of VUS mutations in MYH7 and RYR2 genes in multiple family members highlights the complexity of genetic inheritance in HCM. These findings underscore the challenges in clinical interpretation and risk stratification, as the co-occurrence of mutations in different genes may have synergistic effects on disease severity and phenotype expression. Comprehensive genetic evaluation, including family studies, is crucial for understanding the clinical significance of these mutations and guiding personalized management strategies. Further research is needed to elucidate the impact of VUS mutations on the clinical outcomes of HCM patients.
Abstract 4138620: Assessment of the Accuracy of the Perioperative Mortality Risk in Adults with Congenital Heart Disease (PEACH) Score
Authors: Jon Taylor-Fishwick, Vivian Duarte, Kaitlin Olson, Amber Khanna, Megan SooHoo
Journal: Circulation (2024)

INTRODUCTION: Previous mortality risk scores for adult cardiac surgery patients did not include adult congenital heart disease (ACHD) patients. Development of ACHD specific mortality risk scores include the procedure-specific ACHS score and recently derived PEACH score. While validated in Europe, further evaluation of the PEACH score in additional settings is necessary. RESEARCH QUESTION: We assessed the efficacy of the PEACH score to predict mortality in ACHD patients undergoing congenital cardiac surgery at our institution. We compared the PEACH score to the ACHS and STS scores and assessed for additional risk factors which may further augment the PEACH score. Methods: A retrospective cohort study was conducted of patients who underwent congenital cardiac surgery at the University of Colorado Hospital and Children’s Hospital Colorado between 2010-2022. Patients were identified by the institutional STS congenital cardiac surgery database and were eligible if 18 years or older and underwent congenital cardiac surgery. Components of the PEACH score and additional postulated risk factors were evaluated by univariate analysis. A receiver operating characteristic (ROC) curve was used to compare the PEACH score to existing risk models. Logistic regression analysis determined additional risk factors to augment the PEACH score. Results: A total of 516 patients were included with a median age of 30 (IQR 23-42) and 51% were male. There were nine deaths overall. The PEACH score was predictive of mortality (OR: 2.09, p&lt;0.001) with a score of 0: 0 deaths/240 patients (0%); 1-2: 6 deaths/229 patients (2.6%); 3+: 3 deaths/41 patients (7.3%). Of additional risk factors tested, platelets less than 184,000 per mcL (OR: 8.36, p=0.01) was significantly associated with mortality. Comparison of the models revealed PEACH score AUC 0.832 (95% CI: 0.740,0.924), ACHS score AUC 0.869 (95% CI: 0.806, 0.932), and STAT AUC 0.769 (95% CI: 0.616, 0.922, Figure 1). The addition of platelet level improved the predictive ability of the PEACH score (AUC 0.881). Conclusion: In this single-center analysis, the PEACH score provided strong predictive ability for peri-operative mortality. The addition of platelet levels may further augment this score.
Abstract 4138593: Sex-, Age-and Racial- specific disparities, echocardiographic myocardial mechanics and biomarkers, and 1-year survival among patients with heart failure.
Authors: Mamotabo Matshela
Journal: Circulation (2024)

Background: Heart failure with reduced ejection fraction (HFrEF) is a global health burden affecting millions worldwide, particularly among resource constrained communities. Information is limited regarding addative prognostic relations of sex -, age- and racial- differences, myocardial mechanics and biomarkers, in HFrEF. Aim: Assess prognostic implications of sex-, age- and racial- related disparity in HFrEF; and additive prognostic implications of these parameters to other markers including echocardiography (myocardial mechanics). Methodology: The HFrEF patients’ data were prospectively evaluated during the initial assessment and those hospitalized, and subseguently followed for at least 12months. Patients' KCCQ and EQ-5D-5L Questionnaires were assessed during the initial evaluation and follow-up. Sex, age and racial/ethnic disparities, in-hospital management, follow-ups, health status and 1year mortality were assessed. These parameters were further assessed in addition to biomakers and echocardiographic parameters including LV and RV systolic and distolic strain. Multivariable Cox regression models were fitted to investigate additive prognostic differences. Results: The study population consisted mainly of blacks and major factors were hypertension, diabetes, mitral valve disease, and older age (p&lt;0.0001). Of the initial 2642 screened, only 1883 completed the 1year follow-up visit (mean LVEF 38%). Women were likely to have hypertension, atrial fibrillation and diabetes (p&lt;.001). Rheumatic or valvular heart diseases were more commonly identified among younger, black ethnicity, and males patients. No demonstrated sex differences in functional class and biomarkers including NT-proBNP levels. Men demonstrated significant risk for one-year mortality than women, as was black ethnicity and older age. Impaired strain parameters (RV&gt;LV systolic) were independent risk factors for poor survival, more so when added to sex, racial ethnicity, age and biomarkers i.e. the NT-proBNP levels. Conclusion: The prevalence of HFrEF was higher than anticipated. Men, black ethnicity and older age were associated with a high one-year mortality. Impaired strain (RV&gt;LV systolic) parameters were independent risk factors for poor survival, with additive prognostic implications to sex, racial ethnicity, age and traditional biomarkers. These parameters should be assessed routunely to risk stratify HFrEF patients earlier during their disease course.
Abstract 4138793: Impact of diabetes mellitus on the severity and long-term outcomes of chronic thromboembolic pulmonary hypertension: a retrospective cohort study
Authors: Luyang Gao, sicheng zhang, Xin Li, Sicong Li, qing zhao, Tao Yang, Qixian Zeng, Zhihua Huang, Anqi Duan, Yijia Wang, Zhihui Zhao, Qin Luo, Zhihong Liu
Journal: Circulation (2024)

Background: Previous studies have indicated that diabetes mellitus (DM) is linked to the severity and mortality of both pulmonary thromboembolism and pulmonary arterial hypertension. But the relationships between diabetes and chronic thromboembolic pulmonary hypertension (CTEPH) have not been discussed. This study aims to investigate the relationships of DM with disease severity and clinical worsening events in patients with CTEPH. Methods: We analysed data of patients with CTEPH from the National Center for Cardiovascular Diseases in China between January 1, 2013 and August 31, 2023. A 2-group propensity score matching was conducted to adjust for differences between CTEPH patients with and without DM, employing a 1:1 pairing algorithm. The association between DM and long-term adverse outcomes was appraised utilizing multivariable Cox regression models. Subgroup analyses, predicated on age, sex, World Health Organization functional class (WHO-FC) and body mass index, were carried out to evaluated interaction effects. Results: In total, 489 consecutive CTEPH patients were included in the study, with 25.97% diagnosed with DM. Subsequent matched analysis comprised 127 patients with DM and 127 without DM. CTEPH patients with DM exhibited inferior WHO-FC as well as cardiac index, elevated N-terminal pro–brain natriuretic peptide levels, pericardial effusion, tricuspid annular plane systolic excursion / systolic pulmonary arterial pressure ratio and pulmonary vascular resistance. After adjusting for confounding factors, DM remained independently associated with adverse outcomes in patients with CTEPH. In addition, further subgroup analyses disclosed a more robust association in patients without overweight or obesity. Conclusions: DM correlates with heightened severity of CTEPH and serves as an autonomous predictor of long-term prognosis in CTEPH. Moreover, this correlation is more pronounced in individuals devoid of overweight or obesity.
Abstract 4138624: Looking Beyond Respirophasic Ventricular Interdependence: A Case Report of Constrictive Pericarditis Masquerading as Cirrhosis
Authors: Rongzi Shan, Michael Share, Walid Ayoub, Andrew Lee, Alan Kwan
Journal: Circulation (2024)

Case Presentation: A 67-year-old man with recurrent pleural effusions and concern for cirrhosis was referred for liver transplant. Pleural fluid was transudative by Light’s criteria with a high total protein level of 3.5 g/dL, which made hepatic hydrothorax unlikely. Liver biopsy confirmed congestive hepatopathy without advanced fibrosis. Transthoracic echocardiogram showed left ventricular (LV) ejection fraction 55%, right ventricular (RV) systolic pressure 35 mmHg, normal mitral annular tissue doppler velocities, and early diastolic septal bounce. Right and left heart catheterization showed prominent X and Y descent, elevated and equalized diastolic pressures, but no respiratory discordance in the LV-RV pressure gradient. As etiology of these findings were unclear, he underwent aggressive diuresis and hemodialysis, but repeat right heart catheterization showed persistently elevated right and left filling pressures. Cardiac MRI had no evidence of myocardial or pericardial inflammation/edema but showed pericardial thickening (7.9 mm) and septal bounce. There was no inspiratory septal shift, but the large pleural effusion appeared to limit diaphragm excursion. Given lack of respirophasic ventricular interdependence and thickened pericardium on MRI, CT was ordered, showing pericardial calcifications. Diagnosis of constrictive pericarditis was made, and patient underwent complete pericardiectomy. Pathology confirmed calcified and thick pericardium without acute inflammation. Post-operatively, patient developed RV failure, but recovered with inotrope support and was discharged with improvement in congestive symptoms. Discussion: Constrictive pericarditis classically exhibits respirophasic ventricular interdependence, but large pleural effusions may decrease respiratory variation in intrathoracic pressures, blunting this response. Normal mitral annulus tissue doppler velocities and lack of infiltrative process on cardiac MRI made restrictive cardiomyopathy unlikely. In the absence of respirophasic changes on multimodality testing, constriction can be diagnosed with other supportive features such as diastolic septal bounce, rapid Y descent, diastolic pressure equalization, and pericardial thickening and calcifications.
Abstract 4138731: Clonal Hematopoiesis of Indeterminant Potential is Associated with Pulmonary Arterial Hypertension
Authors: Isaac Emon, Ruaa Al-Qazazi, Michael Rauh, Caitlyn Vlasschaert, Benjamin Ott, Amy McNaughton, Francois Potus, Michael Pauciulo, Alexander Bick, William Nichols, Wendy Chung, Stephen Archer
Journal: Circulation (2024)

Background: Pulmonary Arterial Hypertension (PAH) is a fatal cardiopulmonary disorder characterized by adverse vascular remodelling of small pulmonary arteries, which increases resistance and demand on the right ventricle (RV), ultimately leading to RV fibrosis and failure. Emerging evidence suggests that inflammation plays a crucial role in PAH pathogenesis. Here, we study Clonal Hematopoiesis of Indeterminate Potential (CHIP), a disorder characterized by somatic mutations in genes such as DNMT3A and TET2 , that promotes an inflammatory phenotype, in the development of PAH. Methods: We performed deep, targeted panel sequencing on 1659 PAH patients from the PAH Biobank and 3644 controls (3401 Vanderbilt University Biorepository patients and 243 participants recruited by the Queen’s Genomics Centre at Ongwanada). Variants in known CHIP genes expressed at a variant allele frequency (VAF) &gt; 2% were classified as CHIP. Genes with a VAF &gt; 25% and &lt;50% were considered CHIP if located in reported CHIP hotspot regions. The prevalence of CHIP mutations was compared between controls and PAH patients. Logistic regression was used for statistical analysis. Results: We identified 242 CHIP variants in the 1659 PAH patients. DNMT3A was the most mutated gene (116/242 = 48%), followed by TET2 (46/242=19%). After adjusting for age and sex, we identified a significant association between all CHIP variants combined and PAH (OR: 23.35 [7.67, 71.03]; p&lt;0.0001). Further, DNMT3A CHIP (OR: 25.44 [5.37, 120.40]; p&lt;0.0001), non- DNMT3A CHIP (OR: 26.80 [5.56, 129.23]; p&lt;0.0001) and TET2 CHIP (OR: 13.69 [1.29, 145.30]; p=0.03) were all associated with PAH. A higher proportion of PAH patients under the age of 70 were found to have CHIP variants compared to controls and this was significant for individuals between 60-69 years of age (p=0.037). While there was a 3.8:1 female-to-male ratio of PAH patients, there was a 5.8:1 female-to-male preponderance of DNMT3A variants (p=0.039) (4.3:1 for all CHIP; p=ns), suggesting DNMT3A variants are more common in female patients. The presence of CHIP variants had no significant effect on PAH patient 10-year survival. Conclusion: This research reveals a significant association between CHIP variants, specifically in DNMT3A and TET2, and PAH. The prevalence of CHIP is higher in PAH patients aged 40 to 70 compared to controls and is more common in female patients. These findings suggest that CHIP is a significant risk factor for the development of PAH.
Abstract 4138622: Cardiac Rhabdomyosarcoma: An Updated Review of the English Literature From 1980 Through 2023
Authors: Frank Adusei Poku, Bernice Biney, Samuel Mensah, Sandra Oppong-Twum, Chukwuemeka Aghasili, Joshua Oppong Ampadu, Shawyon Baygani, Joseph Akamah
Journal: Circulation (2024)

Cardiac Rhabdomyosarcoma (CR) is a rare malignant neoplasm of the heart occurring in all age groups and genders. It can arise anywhere in the heart with varied clinical presentation. Available data on CR are mainly from case reports and series that are limited by small sizes. The purpose of this study was to characterize the epidemiology, presentation, management, hospital course, and outcomes of CR published in the English literature from 1980-2023. Methods: We reviewed and included all published case reports with a diagnosis of CR in adult patients (age &gt;18 years) on PubMed and Google Scholar using the keywords “primary cardiac tumor” and “cardiac rhabdomyosarcoma”. Data was extracted onto an Excel spreadsheet for analysis and the outcomes of interest were demographics, clinical presentation, diagnostic modalities, management, complications, and outcomes. We used descriptive statistics to analyze the data. Results: Among a total of 97 patients from 19 countries included in this study, 54% were males and the median age was 49 years (range 18-80). The main symptoms were dyspnea (37.1%), palpitations (23.7%), chest pains (16.5%) and syncope (6.5%). Hypotension or heart failure and arrhythmias were present in 10.3% and 9.3%, respectively and 5.2% had pericardial effusion. In addition to those with metastatic tumors, 22.7% had chronic co-morbidities. The majority of the cases were primary tumors (85.6%), and the remainder were (14.4%). All patients had at least one imaging modality including echocardiography (89%) and CT/MRI (84%). The commonest sites of cardiac involvement were the left atrium (35%), right atrium (33%), right ventricle (20%), and left ventricle (12%). Approximately 68% involved a single cardiac site while 32% involved multiple sites. Among the patients, 96% underwent surgery while 33% and 25% had chemotherapy and 25% radiotherapy, respectively. The median length of hospital stay was 11 days (range, 2-68 days), and mortality was recorded in 79.3% (77/97) of the patients. The median survival time was reported in 42 patients, and it was 6 months (range, 0-36 months). Conclusion: Cardiac rhabdomyosarcoma is a rare and aggressive malignant neoplasm. Most cases are primary tumors with poor outcomes such as a very short median survival time and a very high mortality rate despite the combination of surgery, chemotherapy, and radiotherapy. This calls for further research into the early diagnosis and optimal management strategies to improve outcomes.
Abstract 4138603: Adult-onset Kawasaki Disease: An Updated Review of the English-Language Literature from 1980 Through 2023
Authors: Frank Adusei Poku, Bernice Biney, Samuel Mensah, Joshua Oppong Ampadu, Chukwuemeka Aghasili, Sandra Oppong-Twum, Shawyon Baygani, Henry Okafor
Journal: Circulation (2024)

Introduction: Kawasaki disease (KD) is a pan-vasculitis that primarily affects children and rarely adults. Available data on adult-onset KD are based on case reports and case series, both of which are limited by small sizes. We aimed to characterize the epidemiology, presentation, hospital course, and outcomes of adult-onset KD published in the English literature from 1980 through 2023. Methods: We retrospectively reviewed and included published articles with a diagnosis of KD in patients age ≥18 years. We searched PubMed and Google scholar for case reports/series published in English using the keywords “adult”, “Kawasaki disease”, and “mucocutaneous lymph node syndrome”. We extracted data from individual articles onto an Excel spreadsheet for analysis. Outcomes of interest were the demographic characteristics of patients, clinical presentation and hospital course, management, and complications. Descriptive statistics were used to analyze the data. Results: A total of 137 patients from 29 countries were included in this study. The majority were male (90/137, 64.9%; M:F ratio 1.8) and the median age was 25 years (range, 18-68). The median time to clinical presentation was 5 days (range, 4-60). The main signs and symptoms were fever (95.7%), skin rash (92.9%), conjunctivitis (89.3%), extremity changes (84.3%), oral changes (85.7%), and cervical lymphadenopathy (73.7%). The majority of the patients had no co-morbidities (125/137, 91.2%). EKG changes were not reported in 48 patients (35%). In the remaining 89, 26 (29.2%) had normal EKG or sinus tachycardia, 9 (10.1%) had ST segment elevation, and 9 (10.1%) had arrythmias or abnormal EKGs. Pharmacotherapy included IVIG (80/137, 58.4%), Aspirin (105/137, 76.6%), steroids (31/137, 22.6%) and antibiotics (68/137, 49.6%). For complications, 18.2% (25/137) had aneurysms, 8% (11/137) had myocardial infarction, 10.9% (15/137) had myocarditis, 10% had pericarditis/pericardial effusion, and 10.9% (15/137) had KD shock syndrome. The median length of stay was 14 days (range, 1-60 days). Three patients (2%) died from KD. Conclusion: Adult-onset KD is rare and is associated with significant cardiovascular complications. Clinicians should have high index of suspicion for prompt diagnoses and initiate appropriate treatment to improve outcomes.
Abstract 4138716: A novel Urocortin-2 analog COR-1167 corrects cardiac and renal dysfunction on top of Empagliflozin in a rat model of acute decompensated heart failure
Authors: Yohan Stephan, Clement Corruble, Lucie Charrier, Lionel NICOL, Mark Kowala, Marie-Laure Ozoux, Francesca Lawson, Philip Janiak, Paul Mulder
Journal: Circulation (2024)

Introduction: Urocortin-2 (UCN-2) is a peptide belonging to the corticotropin-releasing factor family that has cardiovascular, renal, metabolic and anti-inflammatory actions and improves cardiac function in human heart failure (HF) and cardiorenal dysfunction in chronic HF models. However, UCN-2 has a short half-life and intravenous delivery limits its therapeutic use. COR-1167 was discovered as a stable UCN-2 analog with qd pharmacological effects when injected subcutaneously. Hypothesis: Whether COR-1167 exerts chronic cardiorenal protection in Acute Decompensated HF (ADHF) is unknown, and in particular on background of SGLT2 inhibition, therefore both treatments were tested in a rat model of ADHF. Methods: Rats had coronary artery ligation to induce MI and a reduced ejection fraction phenotype. Three months later, rats were treated with vehicle or Empagliflozin (Empa) at 10 mg/kg/day PO. One month after starting Empa, two acute decompensation events were induced by administrating NaCl solution (1.8 g/kg, PO) on Day 0 and Day 14. Empa treated ADHF rats received vehicle or COR-1167 (3 µg/kg/day) by SC injections starting at 12 hours after the first decompensation and all treatments continued for 14 days. The groups were ADHF, ADHF + Empa and ADHF + Empa + COR-1167 (n=7-10/group). Left ventricular (LV) hemodynamics (cardiac catheters), cardiac output (echocardiography) and LV tissue perfusion (magnetic resonance imaging), cardiac mitochondrial coupling and ATP production (Seahorse) were measured 1 day after the second decompensation, while urine volume (uVol) and urine Na + excretion (uNa + ) collected from metabolic cages were analyzed 7 days after the first decompensation. Results: Compared to ADHF control rats, Empa treatment had no effect on systolic blood pressure (SBP), cardiac output (CO), LV end systolic pressure volume relationship (LVESPVR), LV end diastolic pressure volume relationship (LVEDPR), mitochondrial coupling and ATP production, but it increased myocardial perfusion, uVol and uNa + excretion. Compared to ADHF + Empa rats, COR-1167 treatment increased SBP, CO, LVESPVR, myocardial perfusion, mitochondrial coupling and ATP production, uVol, uNa + , while decreasing LVEDPVR. Conclusion: In the setting of ADHF, significant cardiorenal benefits and decongestion occurred when COR-1167 was administered on top of an SGLT2 inhibitor.