tbuckley/cabot-search huggingface dataset:
Abstract 15796: Akt1 Y350f Mutation: A Protective Mechanism Against Pulmonary Hypertension, Suppressing Endothelial-to-Mesenchymal Transition in vivo and in vitro
Authors: DINESH BHARTI, Mathews Valuparampil Varghes, Joel James, Alhan M Yazdi, Olga Rafikova, Ruslan Rafikov
Journal: Circulation (2023)

Background: Pulmonary hypertension (PH) is a life-threatening condition characterized by elevated blood pressure in the lungs due to narrowed arteries. Endothelial-to-mesenchymal transition (EndMT) contributes to enhanced proliferation and metabolic changes in the pulmonary arteries of PH patients. Our previous reports have highlighted the role of Akt nitration at tyrosine 350 (Y350) residue in promoting proliferation and metabolic switch in PH models. To investigate the protective potential of inhibiting Akt nitration, we developed a mouse model with a mutation of Akt Y350 to phenylalanine (Y350F), preventing nitration and activation of Akt. Hypothesis: We hypothesized that Akt1 Y350F mutant mice would be protected in preclinical PH models due to inhibited EndMT. Methods: Both mutant Y350F and wild-type Akt1 mice were treated with Sugen5416 (20mg/kg/week i.p.)/hypoxia (10% O2) (Su/Hx) for four weeks to explore pathological mechanisms. Endothelial cells were isolated for in vitro evaluation under EndMT inducers, including Sin-1 chloride and TGF-β1. Results: The wild-type Su/Hx model exhibited vascular remodeling, increased right ventricular systolic pressure (RVSP) (p&lt;0.001), and right ventricular hypertrophy. In contrast, the Akt Y350F mutant model displayed significant protection, with reduced vascular remodeling, pulmonary pressure, and right heart hypertrophy. Akt nitration-induced EndMT markers, TGF-β1 (p&lt;0.05) and TWIST1 (p&lt;0.01), were elevated in wild-type Su/Hx lung tissue. However, the Akt Y350F mutation prevented Akt activation and diminished EndMT markers in the Akt1 Y350F Su/Hx lungs. In isolated cells and lung tissue, induction of EndMT resulted in a progressive PH phenotype, while Akt inhibition exhibited a protective role against PH progression in the Akt Y350F mutant model. Conclusion: Inhibition of Akt nitration through the Y350F mutation restricts vascular remodeling and halts EndMT both in vivo and in vitro. Our findings suggest that strategies targeting Akt nitration could be effective in controlling PH.
Abstract 18549: Focal Pericoronary Adipose Tissue Evaluated by Atomic Numbers on Contrast Spectral Computed Tomography Was Associated With Coronary Arterial Plaques: A Site-by-Site Analysis
Authors: Nobusada Funabashi, Atsushi Shukuya, Hiroki Asano, Akio Kawamura, Naoko Mizuno
Journal: Circulation (2023)

Introduction: Inflammation in pericoronary adipose tissue (PCAT) around the coronary arterial wall causes coronary arterial sclerosis. Many studies evaluated the relationship between total PCAT volume and coronary arterial sclerosis on a patient-by-patient basis. Hypothesis: Inflammation in PCAT may occur focally in coronary arterial system to which coronary arterial plaques localize. Using novel spectral CT, based on atomic number as a new parameter, the focal characteristics of PCAT were evaluated. Methods: 17 patients (10 males, mean age 70 years) underwent cardiac spectral CT (7500, Philips, Tokyo, Japan). From contrast data, atomic numbers of PCAT were determined at a 1) right side site and 2) left anterior side site of a proximal portion of the right coronary arteries (RCA), 3) anterior side site of the left main coronary arteries, 4) left side site of a proximal portion of the left circumflex artery, and left side site of a distal portion of the RCA (five sites each patient). We also evaluated coronary arterial plaques on enhanced CT images at five corresponding sites for which atomic numbers were determined. Results: For a total of 85 sites among 17 patients using enhanced CT, 31 sites had no plaques (group 1), 14 sites had only non-calcified plaques (group 2), 20 sites had only calcified plaques (group 3), 16 sites had mixed plaques (group 4), and four sites had stent implantations (group 5). The mean of atomic numbers for 81 sites, excluding four sites with a stent implantation, were 6.4, 6.8, 6.4, and 6.1 in groups 1-4, respectively (P=NS). For a total of 81 sites, excluding four implantation sites, we evaluated relationship between age and atomic numbers in groups 1-4. Positive correlations were observed in group 1 (R= 0.25) and 3 (R= 0.39), however negative correlation was observed in group 2 (R= -0.37) and 4 (R= -0.40) between age and atomic numbers. No significant differences in atomic numbers were noted between males and females. Conclusions: This is the first study in which focal PCAT was evaluated by atomic numbers and the relationship to coronary arterial plaques determined by site-by-site analysis. This new CT parameter may evaluate the status of PCAT and be a predictor of future occurrence of coronary arterial plaques, which are related to PCAT inflammation.
Abstract 209: The Relationship Between the Ratio of Urine Osmolality to Serum Osmolality and Neurological Outcome of Out-of-Hospital Cardiac Arrest Patients
Authors: Seok Jin Ryu, Dong H Lee
Journal: Circulation (2023)

Background: Progressive hypoxic brain injury after cardiac arrest can affect serum osmolality (SOsm) and urine osmolality (UOsm) in out-of-hospital cardiac arrest (OHCA) patients. This study aimed to examine the association between the ratios of UOsm to SOsm (USRs) within 3 days after return of spontaneous circulation (ROSC) and neurological outcomes in OHCA patients. Methods: The present study was prospective observational study and included OHCA patients with targeted temperature management (TTM) at Chonnam National University Hospital in Gwangju, Korea, between January 2016 and December 2022. We collected SOsm and UOsm at admission and at 24 h, 48 h, and 72 h after ROSC. We assessed the predictive performance of USRs to determine neurological outcome at discharge. Results: A total of 319 patients were included. UOsm levels and USRs at admission and 24 h, 48 h, and 72 h after ROSC in patients with poor outcome were lower than those in patients with good outcome. In multivariable analysis, the USRs at 24 h (odd ratio [OR], 0.363; 95% confidence interval [CI], 0.221-0.594), 48 h (OR, 0.451; 95% CI, 0.268-0.761), and 72 h (OR, 0.559; 95% CI, 0.357-0.875) after ROSC were independently associated with poor neurological outcome at discharge. The area under the receiver operating characteristic curves of USRs at admission and 24 h, 48 h, and 72 h after ROSC for predicting neurological outcome at discharge were 0.615 (95% CI, 0.559-0.669), 0.711 (95% CI, 0.658-0.760), 0.724 (95% CI, 0.671-0.772), and 0.751 (95% CI, 0.699-0.797). Conclusions: The USRs within 3 days of ROSC were associated with poor neurologic outcome at discharge in OHCA patients.
Abstract 17136: Prospective Cohort Study for Evaluating the Safety and Efficacy of Mobile, Motorized Enhanced Extracorporeal Counterpulsation in Refractory Angina Patients
Authors: Jooyeon Lee, Jaewon Oh, In-Cheol Kim, Seonhwa Lee, Se-Eun Kim, Chan Joo Lee, Hyungseop Kim, Seok-min Kang
Journal: Circulation (2023)

Introduction: Enhanced external counterpulsation (EECP) therapy is a potential treatment for refractory angina, which refers to persistent symptoms despite optimal treatment. However, the immobility, cost, and lack of individualized pressure control limit the accessibility and clinical implications of EECP. To address these limitations, a new Mobile, Motorized Enhanced Counterpulsation (MECP) device has been developed. Hypothesis: To investigate efficacy of MECP in improving in angina functional class and exercise tolerance in patients with refractory angina and to validate the consistency in outcomes observed with conventional EECP treatment. Methods: This prospective study enrolled patients with symptomatic refractory angina between September 2020 and December 2022 at two tertiary centers in Korea. Baseline and post-treatment assessments included measurements of angina scale, 6-minute walking test, cardiopulmonary exercise test, and central arterial pressure. Results: The study included 71 patients (70.4% male, median age 66 years). After the 10-hour MECP treatment session, 57.7% of patients showed improvement in angina scale based on Canadian Cardiovascular Society classification, with a significant distribution change from 76.8% to 49.3% in class II and from 21.7% to 5.7% in class III (p&lt;0.001). Furthermore, patients demonstrated an increase of 20 meters in the 6-minute walk distance after MECP treatment (464 meters vs. 484 meters, p&lt;0.001). However, there were no statistically significant differences in the baseline characteristics of patients based on their response to MECP. Conclusion : Our study highlights the substantial benefits of MECP in relieving symptoms for patients with refractory angina and suggests its potential for broader clinical applications which merits further investigation.
Abstract 16384: Interaction of Socioeconomic Status With Polygenic Risk for Coronary Artery Disease in a Novel Biobank
Authors: Lekha Pandya, Nicolas Ledru, Nathan O Stitziel
Journal: Circulation (2023)

Introduction: Socioeconomic status (SES) has a measurable and significant impact on cardiovascular disease incidence and outcomes. Study of its potential interactions with other known risk factors, such as genetics, remains an area for further research. Aim: To examine the interaction of polygenic risk for coronary artery disease (CAD) with socioeconomic status, as represented by income bracket. Methods: We utilized the NIH All of Us biobank, which integrates whole genome sequencing, electronic health record, and survey data. A previously-validated PRS for CAD (Inouye et al., 2018) was calculated for each patient. We subsetted the sample into high, medium, and low genetic risk groups per z-scores for the PRS: z-score &gt;1, between 1 and -1, and &lt;-1 respectively. Income information was derived from the survey data. Multivariable logistic regression was used to assess the performance of the PRS in this sample, with outcome defined as presence of CAD. The model was adjusted for PRS, age, gender, and the first 4 principal components of ancestry. Both income and the interaction of PRS by income were included as covariates. Results: In this sample of 97,405 individuals, this PRS is strongly associated with CAD prevalence: adjusted odds ratio for CAD per SD of the PRS was 1.96 (95% CI, 1.83-2.10). We then observed a differential effect of income on CAD. In the low and medium genetic risk groups, increasing income was associated with lower CAD prevalence. In the high genetic risk group, this protective effect was lost and CAD prevalence was overall similar across income brackets. Conclusions: These findings suggest a complex interaction between genetic risk of CAD and SES. High risk individuals may not derive the same benefit of improved SES and its material benefits. This unique subgroup will require uniquely targeted interventions, highlighting the need for deeper study of genetic risk in order to actualize the promises of precision medicine.
Abstract 14039: Therapeutic Potential of Beta Hydroxybutyrate in Nonalcoholic Fatty Liver Disease (NAFLD)-Induced Cardiovascular Disease
Authors: Olufunto O Badmus, Lucy C Taylor, Jennifer R Greer, Karis E McGowan, Terry Hinds, David E Stec
Journal: Circulation (2023)

Background: Cardiovascular disease (CVD) is the leading cause of mortality in non-alcoholic fatty liver disease (NAFLD). Beta hydroxybutyrate (BHOB), a liver metabolite, is the major ketone that serves as an alternative fuel source in the body. Our previous studies show that hepatocyte peroxisome proliferator activator receptor-α knockout (Ppara HEPKO ) mice, model of NAFLD-induced CVD, exhibit reduced circulating levels of BHOB. Hypothesis: We hypothesized that restoring plasma BHOB levels will improve cardiovascular function in Ppara HEPKO mice. Aims: To determine the therapeutic role of BHOB in NAFLD-induced CVD. Methods: 30 weeks old male Ppara HEPKO mice were given 1,3 butanediol (20% in drinking water) (Ppara HEPKO + BHOB) or vehicle (Ppara HEPKO ) (n=6) for 6 weeks. Plasma BHOB was measured at baseline and after treatment. Cardiac structure and function were measured by high resolution ultrasound echocardiography (VEVO 3100), using the B-mode, M-mode, pulse wave and tissue doppler at baseline and after treatment. Mean arterial blood pressure was measured by radiotelemetry. Liver fat was determined by EchoMRI, Oil Red O staining and hepatic triglyceride levels. Results: After 6 weeks of BHOB treatment, Ppara HEPKO exhibit increased plasma BHOB compared to baseline (0.5 ± 0.01 vs. 0.2 ± 0.02mmol/L), attenuated arterial blood pressure compared to control (109 ± 3 vs. 121 ± 4mmHg), improved systolic function: cardiac output (13.8 ± 0.8 vs. 11.1 ± 0.7ml/min), stroke volume (31.1 ± 2.1 vs. 23.4 ± 1.3ml/min), improved diastolic function: isovolumic relaxation time (18.7 ± 0.8 vs. 20.6 ± 0.9m/sec), E/e’ (-29.6 ± 0.9 vs. -32.4 ± 1.4), and attenuated vascular stiffness. Interestingly, BHOB did not alleviate hepatic fat compared to control as demonstrated by EchoMRI (0.8 ± 0.3 vs. 0.7 ± 0.3), hepatic triglyceride (1.4 ± 0.3 vs. 1.3 ± 0.2mM) and Oil Red O staining. Conclusion: Our findings indicate that BHOB treatment improves arterial blood pressure, systolic, diastolic, and vascular function in, Ppara HEPKO knockout mice. However, BHOB did not alleviate hepatic steatosis suggesting that BHOB improves cardiovascular function in Ppara HEPKO mice independent of changes in hepatic fat content.
Abstract 13315: Recurrent Cardiac Tamponade Due to Minoxidil Associated Drug Induced Lupus Erythematosus
Authors: Michel Juarez, Juthipong Benjanuwattra, Alejandro Herrera Ramos, Marina Iskandir, Mohammad Ansari, Scott W Shurmur
Journal: Circulation (2023)

Case description A 59 year old man with history of MGUS, CKD stage 2, DM, HTN, and OSA presented with gradual worsening of dyspnea and intermittent dizziness over the past few days. Echocardiography showed diastolic collapse of the RV, RA collapse, IVC plethora, marked tricuspid in-flow velocities, and pericardial effusion suggestive of cardiac tamponade (CT). Subxiphoid pericardial window was emergently performed. Serosanguineous fluid 900 mL was drained, and fluid analysis was negative for malignancy or infection. Pericardial biopsy revealed fibro-connective tissue with mild peri-vascular chronic inflammation. He significantly improved and was discharged after 5 days. One month later, he presented again with 1 day symptom of severe dyspnea due to recurrent pericardial effusion with CT physiology. Emergent pericardiocentesis was performed to remove 1,800 ml of serous fluid. Serologic workup for autoimmune disease was strongly positive for anti-histone antibody. ESR (124 mm/hr) and c-reactive protein (5.8 mg/dL) were elevated. Upon review of prescription list, he had been treated for HTN in the past 5 years with minoxidil, amlodipine, lisinopril, and carvedilol. Discussion The use of topical minoxidil, a potent peripheral arterial vasodilator, has been approved for androgenetic alopecia in both men and women for decades, whereas oral minoxidil is limited to refractory hypertension due to side effects such as reflex tachycardia, fluid retention, hypertrichosis, and, rarely, idiosyncratic pericardial effusion. Pericardial effusion was reported in approximately 3-5% of patients receiving minoxidil therapy, which could be attributed to volume overload associated with underlying renal insufficiency. Besides hydralazine, another direct arterial vasodilator commonly implicated in drug-induced lupus erythematosus (DILE), minoxidil also carries a trivial risk of DILE, as suggested by a positive anti-histone antibody and biopsy-proven serositis. Although the association between topical minoxidil and pericardial effusion has never been reported, receding hairline has become a major cosmetic concern and the clinicians should be aware of this rare, but serious, complication associated with minoxidil due to its widespread use.
Abstract 15327: Clinical Outcomes of Methamphetamine-Associated Cardiomyopathy Compared to Ischemic Cardiomyopathy: A Single Institution Retrospective Longitudinal Study
Authors: Michelle Sung, Hannah Bernstein, Khanhphi Tranvu, Edward Chau, Shamili Allam, Carter English, Dali Fan, Bilal Munir, Uma N Srivatsa
Journal: Circulation (2023)

Background: Methamphetamine-associated cardiomyopathy (MAC) leads to significant morbidity and mortality. The benefit of implantable cardioverter-defibrillator (ICD) in this population is poorly characterized. Aims: To evaluate ICD use and outcomes in patients with MAC compared to ischemic cardiomyopathy (ICM). Methods: Electronic health record (EHR) was queried for all heart failure hospitalizations using ICD-9 codes between 2011 and 2019. Patients with an EF ≤ 35% were included. The MAC cohort was derived from this population and defined by ICD-9 code or positive urine toxicology and compared to ICM cohort. Baseline characteristics and outcomes were extracted from the EHR. MACE was defined as death, ventricular tachycardia, cardiac arrest, rehospitalization, atrial fibrillation (AF) or stroke. Results: The study included 294 patients in the MAC group and 373 patients in the ICM group. MAC patients were younger (56 vs 61 years, p&lt;0.001) compared to ICM (table 1). Readmission rates for heart failure at one year were similar (13% vs 11.2%, p=ns). Significantly fewer patients with MAC had ICD for primary prevention (15.0% vs 27.9%, p&lt;0.001). Mortality and AF were lower in MAC compared to ICM, however VT (2.38% vs 5.09%, p=0.072) and cardiac arrest (6.1% vs 7.8%, p=0.408) were similar between the two groups. MACE outcomes were worse in the ICM cohort (38.3% vs 21.1%, p=0.012) than MAC. In the MAC cohort, ICD presence was associated with 56.82% incidence of MACE compared to 40.00% without ICD (OR = 1.97, CI 1.032-3.77, p = 0.040) mainly due to higher AF hospitalization (22% vs 8%, p=0.01). Conclusion: ICM patients had higher mortality and atrial fibrillation compared to MAC. ICD implantation for primary prevention was not associated with reduced mortality, however this cohort had higher AF hospitalization. We need further studies to assess the benefit of ICD in MAC.
Abstract 17817: Deep Learning-Based Retinal Imaging for Predicting Cardiovascular Disease Events in Prediabetic and Diabetic Patients: A Study Using the UK Biobank
Authors: Chan Joo Lee, Tyler H Rim, Hyun Goo Kang, Sung Soo Kim, Geunyoung Lee, Marco Yu, Yih-Chung Tham, Ching-Yu Cheng, Sung Ha Park
Journal: Circulation (2023)

Introduction: Our previous work led to developing a deep learning algorithm for retinal images, Reti-CVD, which effectively predicted cardiovascular disease (CVD) events in individuals without CVD history, leveraging coronary artery calcium (CAC) scores for algorithm training. Hypothesis: This study aims to assess the capability of deep learning-assisted retinal imaging to predict CVD events among prediabetic and diabetic patients using the data from the UK Biobank. Methods: Our study included prediabetic and diabetic patients from the UK Biobank. Reti-CVD scores were calculated and categorized into three risk groups - low (n=550), moderate (n=276), and high (n=275), based on the 50th and 75th percentiles, following a 2:1:1 ratio. To assess the Reti-CVD's ability in predicting fatal and non-fatal CVD events, we performed a survival analysis on the longitudinal data from the UK Biobank using Cox proportional-hazards models and hazard ratios (HRs). Results: Among the 1101 prediabetic or diabetic patients at the onset, 138 (12.5%) experienced CVD events. According to Reti-CVD scores, these events were found as 8.2% (45/550), 15.2% (42/276), and 18.5% (51/275) in the low, moderate, and high-risk groups over a median follow-up period of 11 years, respectively. After adjusting for factors such as age, gender, hypertensive medication use, statin use, and smoking history, a significant association was observed between the Reti-CVD and the incidence of CVD events (HR=1.57, 95% CI, 1.00-2.47 for the moderate-risk group; HR=1.88, 95% CI, 1.19-2.98 for the high-risk group compared to the low-risk group). An increasing HR trend of 1.36 (95% CI, 1.09-1.70) was observed across risk groups in the prediction of CVD events. Conclusions: The Reti-CVD offers a valuable tool for risk stratification among prediabetic and diabetic patients, indicating its potential in managing these high-risk groups.
Abstract 17851: Prevalence and Predictors of Early Left Ventricular Functional Recovery After Transcatheter Aortic Valve Implantation: The TAVI-NOR Study
Authors: Abukar M Ali, Daanyaal Wasim, Oyvind Bleie, Kjetil H Løland, Erik J Packer, Svein Rotevatn, Sahrai Saeed
Journal: Circulation (2023)

Introduction: Pre-intervention left ventricular (LV) ejection fraction (LVEF) in aortic stenosis (AS) patients has prognostic value. However, the hemodynamic changes early after TAVI (transcatheter aortic valve implantation) is not fully explored. Hypothesis: To what extent early functional recovery by a clinically significant increase (≥10%) in LVEF is achievable following TAVI, how it differs from baseline patient characteristics, and its potential prognostic impact. Methods: Between 2012 and 2019, 600 consecutive patients (age 81±6years, 49.3% females) with clinically significant AS underwent TAVI. Echocardiography was performed before and within 8 weeks after TAVI. Variables associated with &lt;10% LVEF improvement were identified. End-points were ≥10% LVEF improvement and all-cause mortality. Results: From baseline to follow-up; 28% of patients achieved ≥10% LVEF improvement. A ≥10% LVEF improvement was observed in 25% of patients with normal baseline flow (indexed stroke volume ≥35ml/m 2 ) versus 38% in low-flow (p=0.002). Impaired kidney function, higher blood pressure (BP), higher baseline LVEF and indexed stroke volume, and lower LV mass was more likely in patients with &lt;10% LVEF. In a multivariate logistic regression analysis, higher baseline systolic BP (OR 1.02; 95% CI 1.01-1.03, p=0.004) and lower LV mass (OR 1.25; 95% CI 1.02-1.54, p=0.031), and new pacemaker implantation (OR 1.55; 95% CI 0.99-2.42, p=0.055) were associated with a higher risk, and baseline LVEF &lt;50% with a lower risk (OR: 0.15; 95% CI: 0.09-0.25) for &lt;10% LVEF improvement following TAVI, independent of CKD, baseline troponin T and NT-proBNP. In a univariate Cox regression model, &lt;10% increase in LVEF in early phase after TAVI was not a significant predictor of mortality (HR 1.16; 95% CI 0.90-1.50, p=0.258). Conclusions: Clinically significant early LV functional recovery was evident in nearly one-third of severe AS patients, especially patients with reduced LVEF and more symptoms at baseline. Higher systolic BP, lower LV mass, and the need for new permanent pacemaker, were independently associated with a higher risk of not achieving early LV function recovery after TAVI. In long-term follow-up early LV functional recovery was not associated with all-cause mortality.