tbuckley/cabot-search huggingface dataset:
Abstract 15693: Weekend Sleep Extension (Catch-up Sleep) is Associated With Lower Incidence of Coronary Calcium Score: <i>The Elsa-Brasil Study</i>
Authors: Érique José Peixoto de Miranda, Barbara Khonangz Parise, Ronaldo Santos, Soraya Giatti, Aline Nogueira Aielo, Lorenna Cunha, Wagner A Silva, Silvana Souza, Paulo A Lotufo, Isabela M Bensenor, Marcio Bittencourt, Luciano F Drager
Journal: Circulation (2023)

Background: Insufficient sleep is a worldwide public health problem with potential cardiovascular consequences. Therefore, strategies aiming at improving sleep patterns are highly desired. Cross-sectional studies showed that weekend sleep extension (catch-up sleep) is associated with better glucose metabolism and cognitive function profiles, but longitudinal studies are lacking. Hypothesis: Catch-up sleep may have protective effects on subclinical atherosclerosis. Methods: In this prospective cohort study, we performed a 7-days wrist actigraphy for monitoring sleep duration and a sleep study to detect sleep apnea. Catch-up-sleep was measured by calculating weekend sleep duration (Friday-Saturday nights) minus weekday sleep duration (Sunday-Thursday nights). Coronary artery calcium, CAC (64-slice multi-detector computed tomography) was measured at two different time points throughout the study (baseline, between 2010-2014, and follow-up, between 2016-2018). Incidence of subclinical atherosclerosis was defined as baseline CAC=0 followed by CAC&gt;0 at a 5-year follow-up visit. The association of incident CAC outcome was assessed using logistic regression adjusting for age, sex, race, body mass index, hypertension, diabetes mellitus, smoking, low- and high-density lipoprotein, use of statin, sleep apnea and interscan period). Analysis of incidence was Inverse probability censoring weighted. Results: We analyzed 1,832 participants with available CAC scores at baseline (age: 48.8±8.0years; 57.8% women; 32.1% with sleep apnea). The mean sleep duration was 6.6±1.0 hours. Catch-up-sleep &gt;90 minutes was observed in 28.0%. Incidence of CAC was 27/141 (19.1%) among subjects with catch-up-sleep &gt;90 minutes and 326/1029 (31.7%) among those with catch-up-sleep ≤90 minutes (P&lt;0.001). In covariate-adjusted analyses (n=1,170, follow-up=5.4±0.90 years), we found a lower incidence of CAC in those participants with weekend sleep extension &gt;90 minutes (OR=0.62; 95% CI 0.52-0.74). Conclusion: Catch-up sleep is independently associated with a lower incidence of CAC. These results underscore that catch-up sleep may mitigate the adverse cardiovascular effects of weekdays sleep restrictions frequently observed in our Society.
Abstract 13395: Dapagliflozin Reduces Myocardial Sodium Content and Correlates With Reverse Cardiac Remodeling in Nondiabetic Patients With Heart Failure and Preserved Ejection Fraction (Dapa-Sodium)
Authors: carlos A plata, Armando Vernaza, Iván E Yela-Muñoz, Maria E Casanova-Valderrama
Journal: Circulation (2023)

Introduction: Myocardial sodium overload is a major determinant of adverse cardiac remodeling in heart failure (HF). Sodium tissue content by 23Na magnetic resonance imaging (23Na-MRI) has been validated in human studies. SGLT-2 inhibition blocks sodium reabsorption in renal proximal tubular cells with remarkable cardiovascular outcomes in HF due to mechanisms not yet fully understood. Hypothesis: SGLT-2 inhibition will decrease myocardial sodium content and it will correlate with reverse remodeling in HFpEF. Aim: To determine whether Dapagliflozin leads to decreased myocardial sodium content and reverses pathological hypertrophy in HFpEF. Methods: Prospective, single-center, open-label study of sixty nondiabetic outpatients with HFpEF underwent baseline 23Na-MRI and initiated with dapagliflozin 10 mg once daily according to GDMT. Absolute changes in myocardium relative sodium signal intensity (rSSI) and left ventricular mass index (LVMi) were analyzed from baseline and at 3-month follow-up with 23Na-MRI. Results: All patients exhibited significantly high baseline myocardium rSSI [0.32 (0.28, 0.34)]; 66% above median [0.24 (0.20, 0.27), P = 0.004], decreasing -30% to [0.27 (0.22, 0.30), P&lt;0.001] at 3 months with Dapagliflozin therapy. These changes were correlated with a significant reduction in LVMi of -13 g/m 2 [from 84 g/m 2 (72, 120) to 71 g/m 2 (63, 95), P&lt;0.001]. Conclusions: Dapagliflozin reduces myocardial sodium content and reverses pathological hypertrophy in patients with HFpEF. These findings suggest that SGLT-2 inhibition acts directly on cardiomyocytes and explains the cardioprotective effects demonstrated though large randomized trials.
Abstract 14312: Comparison of Machine Learning and Conventional Statistical Modeling for Predicting Readmissions Following Acute Heart Failure Hospitalization
Authors: Karem Abdul-Samad, Shihao Ma, Alice Chong, Chloe X Wang, Xuesong Wang, Peter C Austin, Joan Porter, Heather J Ross, BO WANG, Douglas S Lee
Journal: Circulation (2023)

Introduction: Developing accurate models for predicting risk of 30-day readmission has been a major healthcare interest. Evidence suggests that models developed using machine learning (ML) may have better discrimination than conventional statistical models (CSM), but the calibration of such models is unclear. Objectives: To compare models developed using CSM or ML to predict 30-day readmission for cardiovascular and non-cardiovascular causes in HF patients. Methods: We studied 10,919 patients with HF (&gt; 18 years) discharged alive from a hospital or emergency department (2004-2007) in Ontario, Canada, linked to administrative databases for hospitalization and vital status resulting in complete follow-up. The study sample was randomly divided into training and validation sets in a 2:1 ratio. CSMs to predict 30-day readmission were developed using Fine-Gray subdistribution hazards regression (treating death as a competing risk), and the ML algorithm employed random survival forests. Models were evaluated in the validation set using both discrimination and calibration metrics. Results: In the validation sample of 3602 patients (median age 76 [IQR, 67-82] years, 46.6% females), Random Survival Forests (c-statistic = 0.620) showed similar discrimination to the Fine-Gray competing risk model (c-statistic= 0.621) for 30-day cardiovascular readmission. In contrast, for 30-day non-cardiovascular readmission, the Fine-Gray model (c-statistic= 0.641) slightly outperformed the random survival forests model (c-statistic = 0.632). For both outcomes, The Fine-Gray model displayed better calibration than random survival forests when deciles of observed vs. predicted risks were compared (Panels A-D). Conclusions: In HF patients, time-to-event analysis of outcomes using Fine-Gray models had similar discrimination but superior calibration to ML model, highlighting the importance of reporting calibration metrics for ML-based prediction models.
Abstract 12901: ADAR1 RNA Editing in Vascular Smooth Muscle Maintains Vascular Integrity, Regulates Cell State Transition, and is a Novel Mechanism of Coronary Artery Disease Risk
Authors: Chad S Weldy, Qin Li, Hongchao Guo, Drew Galls, Paul Cheng, Joao P Monteiro, Markus O Rasanen, Daniel Li, Brian Palmisano, Disha Sharma, Matthew Worssam, Wenduo Gu, Amruta Bhate, Ramendra K Kundu, Trieu Nguyen, Jin Billy Li, Thomas Quertermous
Journal: Circulation (2023)

Adenosine-to-inosine (A-to-I) RNA editing is a common RNA modification catalyzed by ADAR (adenosine deaminase acting on RNA) enzymes. ADAR1 serves a crucial function to edit specific immunogenic double stranded RNA (dsRNA) molecules to prevent the dsRNA sensor, MDA5 ( IFIH1 ), activating an interferon stimulated gene (ISG) response. Discoveries in human genetics now implicate deficient ADAR1 RNA editing as a causal mechanism in coronary artery disease (CAD). Here, we reveal in human atherosclerosis, smooth muscle cells (SMCs) express immunogenic dsRNA at markedly higher levels compared to all other cell types. We demonstrate that ADAR1 is the master regulator of RNA editing in primary human coronary artery SMC (HCASMC). Loss of RNA editing through ADAR1 KD in HCASMC causes an ISG response characterized by upregulation of ISG genes (i.e. ISG15, IFI6, IFIH1 ) in addition to genes with known roles in SMC phenotypic transition and CAD risk (i.e. KLF4 , TCF21 , and ZEB2 ). ADAR1 and MDA5 regulate SMC phenotypic modulation and calcification in vitro and in atherosclerosis prone mice. scRNAseq analysis reveals SMC to have increasing ISG expression as cells transition from mature SMC to a more calcified chondromyocyte phenotype. To further evaluate the role for SMC RNA editing in vivo , we generated a conditional SMC specific Adar1 KD mouse ( Adar1 flox/flox , Myh11 CreERT2 , ROSA tdT/+ , ApoE -/- ). At 2 weeks following SMC- Adar1 KD, we observe 50% mortality, where mice demonstrate a severe phenotype of elastin degradation and disarray, intravascular hemorrhage, and inflammatory cell infiltration in the aortic wall. This effect was not seen with an endothelial cell specific deletion model ( Adar1 flox/flox , Cx40 CreERT2 ). scRNAseq of aortic tissue shows that SMC- Adar1 KD causes ISG activation throughout the vessel wall, SMCs show loss of mature SMC markers, and there is robust macrophage and T cell infiltration. Through evaluation of ligand-receptor interaction, we show that Ccl5:Ccr5 is the principal regulator of cell infiltration following SMC- Adar1 KD. Here we provide key evidence to support the observations from human genetics that the ADAR1-dsRNA-MDA5 axis is a causal mechanism in vascular disease and warrants further investigation.
Abstract 17216: Limited Concordance of Core Lab Left Ventricular Ejection Fraction With Automated Assessments: A Sub-Study From VALOR-HCM
Authors: Gary Parizher, Wael A Jaber, Anjali T Owens, Kathy E Wolski, Jeffrey B Geske, Sara Saberi, Andrew Wang, Mark Sherrid, Neal K Lakdawala, Michael A Fifer, David R Fermin, Srihari S Naidu, Nicholas G Smedira, Hartzell Schaff, Ellen McErlean, Christina M Sewell, Kathy L Lampl, Amy J Sehnert, Steven E Nissen, Milind Y Desai, Paul C Cremer
Journal: Circulation (2023)

Introduction: The performance of automated left ventricular ejection fraction (LVEF) assessment in patients with altered cardiac chamber geometry, such as those with obstructive hypertrophic cardiomyopathy (HCM), is not well described. Aims: Accurate assessment of LVEF is required for dose titration and continuation of myosin inhibitors in obstructive HCM. From the VALOR-HCM trial (NCT04349072), the agreement of two commercially available software packages was compared with blinded core lab assessment of LVEF. Methods: From baseline and week 16, among 112 patients randomized to either mavacamten or placebo, 178 echocardiograms were analyzed. Representative clips were manually selected, and automated LVEFs were calculated. Comparisons of LVEFs were made using Pearson’s correlation coefficients and Bland-Altman analysis. Results: With core lab assessment, the overall median LVEF was 68% (Q1 66%, Q3 70%). The correlation with vendor 1 was moderate (r = 0.47, 95% CI 0.35-0.58, p &lt;0.001) and weak with vendor 2 (r =0.21, 95% CI 0.07-0.35, p =0.004). Correlation was also weak between vendor 1 and 2 (r = 0.14, 95% CI 0.00-0.28, p = 0.06). Vendors 1 and 2 had an underestimation bias of LVEF of 8% (95% CI 6-9%) and 8% (95% CI 7-9%), respectively, compared to core lab LVEF (Figure 1). Conclusions: In VALOR-HCM, the concordance of LVEF between different commercially available software packages with each other and with a core lab assessment was limited. Further study is needed to evaluate and improve the performance of automated LVEF tools in obstructive HCM patients who have altered cardiac chamber geometry.
Abstract 12812: Temporal Trends of Calcium Modification Therapies in Chronic Total Occlusion Percutaneous Coronary Intervention
Authors: Spyridon Kostantinis, Athanasios Rempakos, Bahadir Simsek, Judit A Karacsonyi, Salman S Allana, Michaella Alexandrou, Rhian Davies, sevket gorgulu, Khaldoon Alaswad, Mir B Basir, Jaikirshan Khatri, Paul Poommipanit, James Choi, Luiz Ybarra, Rodrigo Bagur, Niranjan Reddy, Korhan Soylu, Ufuk Yildirim, MITUL P PATEL, Ehtisham Mahmud, Lorenzo Azzalini, Kathleen Kearney, Ahmed M Elguindy, Nidal Abi Rafeh, OMER GOKTEKIN, Olga Mastrodemos, Bavana V Rangan, Yader Sandoval, M Nicholas Burke, Emmanouil S Brilakis
Journal: Circulation (2023)

Introduction: Various techniques with different mechanisms of action are presently available for the modification of coronary calcium in chronic total occlusions (CTOs). Hypothesis: We sought to examine the temporal trends in the use of calcium modification therapies in a large multicenter CTO percutaneous coronary intervention (PCI) registry. Methods: We analyzed data from 13,079 CTO PCIs performed in 12,799 patients at 46 US and non-US centers between 2012 and 2023. Calcification was assessed by angiography as mild (spots), moderate (involving ≤50% of the reference lesion diameter), or severe (involving &gt;50% of the reference lesion diameter). Results: Moderate or severe calcification was present in 6,094 CTOs (46.6%). Among CTO lesions with moderate or severe calcium, one or more calcium modification techniques was used in 1,006 cases (16.9%); rotational atherectomy (7.2%, n=434), laser atherectomy (3.4%, n=203), intravascular lithotripsy (IVL) (3.4%, n=200), scoring balloon (3.0%, n=178), cutting balloon (1.8%, n=109), orbital atherectomy (1.5%, n=91), and Chocolate balloon (Teleflex, 0.3%, n=15). Over time, the use of calcium modification techniques for lesions with moderate to severe calcification increased from 2.5% in 2012 to 25.7% in 2023 (p for trend &lt;0.001), with a significant increase in the use of IVL (from 0.6% in 2020 to 16.6% in 2023; p for trend &lt;0.001) (Central Illustration). In the last 2 years (2021-2023), IVL was the most commonly used calcium modification technique followed by rotational atherectomy. Conclusions: The use of calcium modification techniques for calcified CTO lesions increased over time, with a significant increase in the use of IVL in the last years.
Abstract 18989: Neonatal Arch Reconstruction via Sternotomy or Thoracotomy: A Propensity Score Matched Analysis
Authors: Peter Chiu, Addison Gearhart, Supreet Marathe, Margaret Holland, Shinichi Goto, Sunil J Ghelani, Aditya K Kaza
Journal: Circulation (2023)

Introduction: For neonatal repair of coarctation of the aorta, patients may either undergo thoracotomy or sternotomy with cardiopulmonary bypass. While some guidance exists, the optimal approach remains poorly defined. Methods: This is a single center retrospective cohort study from 7/05 through 5/22 including patients who underwent neonatal aortic arch reconstruction for isolated coarctation of the aorta and excluding genetic syndromes, heterotaxy, and right aortic arch. Propensity score was estimated using demographic and anatomic variables and 1:1 optimal matching was performed. Primary outcomes were reintervention, either open or catheter-based, and survival. A hazard spline was constructed in order to assess the effect of varying distal arch size on hazard of reoperation (Figure 1). ICU and Hospital length of stay were secondary outcomes. Results: There were 263 patients who underwent isolated coarctation repair during the given time period. Matching yielded 50 patient pairs (n = 100). In the propensity matched population, one patient died and 11 patients underwent reintervention, with 2 of these patients undergoing 2 reinterventions. The interaction between distal transverse arch size and operative approach (sternotomy vs. thoracotomy) was statistically significant, p &lt; 0.05 for interaction. Among patients with a distal arch z-score &lt; -3.5, there appeared to be an advantage to sternotomy. With a distal arch z-score &gt; -3.5, patients undergoing sternotomy appeared to have a disadvantage with respect to risk for reintervention. ICU length of stay was greater for patients undergoing sternotomy, 5.9 days [IQR: 4 to 12.6] vs 2.8 days [IQR: 1.7 to 4.2], p &lt; 0.001, as was hospital length of stay, 14.3 days [IQR: 11 to 23.7] vs 6.5 days [IQR: 5.2 to 9.8], p &lt; 0.001. Conclusions: Patients with a distal arch z-score larger than -3.5 may benefit from thoracotomy, and those with a distal arch z-score smaller than -3.5 may benefit from sternotomy.
Abstract 12860: A Novel Cardiac Presentation of a Genetic Syndrome
Authors: Parth A Shah, Bishal Bhandari, Amro Alsaid
Journal: Circulation (2023)

Introduction: Cute Syndrome is caused by a missense mutation in SCN8-A which encodes voltage gated sodium channel alpha subunit 8 (Nav1.6). Gain of function mutations trigger epileptic encephalopathy, while loss of function mutations are associated with cerebellar ataxia and cognitive problems 1 . While these channels are essential for progression of action potentials across the cardiac circuit, SCN8-A mutations are not associated with arrhythmias. Meanwhile, SCN5-A mutations have been implicated in heart block, LQTS, Brugada syndrome, and ventricular fibrillation. Here we describe a case of heart block and sinus node dysfunction in a patient with SCN8-A mutation. Presentation: A 19 year old male with past medical history of SCN8A mutation admitted for characterization of seizures. He has had focal seizures since the age of 13 with multiple admissions for seizures. He had new staring spells with shaking of his hands and inability to walk multiple times a week. He was admitted for Long Term EEG and was noted to have two episodes of loss of consciousness with progressive bradycardia followed by sinus pauses. He urgently had a temporary pacemaker placed followed by placement of a PPM. He has remained seizure free since his PPM implantation. Discussion: Voltage gated Sodium channels are an integral part of the cardiac action potential. SCN8-A encodes Nav1.6. A mutation in this gene, primarily expressed in neurons but has also been seen in cardiac tissue, could cause arrhythmias. Human mutations have been associated with intellectual disabilities and seizure disorders 1,2,3 . Mouse models have shown that null mice have prolonged cardiac action potentials, suggesting role in cardiac arrythmias 4 . There have been no documented human cases of SCN8-A mutations with arrhythmias. Our patient's seizures were thought to be due to the neurological manifestations of his mutation. Evaluation of cardiac and EEG monitoring determined that sinus pauses preceded seizures, and he has been seizure free since his PPM. This case demonstrates the need for further research to characterize cardiac manifestations of SCN8-A mutations and patients with the mutation may benefit from further cardiac evaluation.
Abstract 16414: Prognostic Value of Exercise Tolerance and Exercise-Associated Diastolic Dysfunction in Elderly Patients Referred for Exercise Stress Echocardiography
Authors: Joseph Elias, Swiri Konje, Alba Munoz, Ga Hee Kim, Kruti Gandhi, Errol C Moras, Christopher Perez Lizardo, Arpanjeet Kaur, Alaa Omar, Edgar Argulian
Journal: Circulation (2023)

Aim: We studied the prognostic value of exercise tolerance, measured in metabolic equivalents of tasks (METs), and exercise-associated diastolic dysfunction (Ex-DD) in elderly patients referred for exercise stress echocardiography (ExE). Methods: Retrospectively, 583 patients (70±6 years, 57% women, EF: 61±5%) who underwent ExE using the Bruce protocol and were ≥60 years of age were included and followed for death or cardiac hospitalization. Ex-DD was defined as the presence of abnormal resting tissue Doppler mitral annular velocity (e') and post-exercise E/e' ratio. Results: During a median follow-up period of 3.7 years, 13 patients died, 70 were hospitalized, and 77 had combined outcome. 151 (26%) patients had Ex-DD and had more combined outcome compared to no Ex-DD (29 [19%] vs. 48 [11%], p=0.01). The average workload during ExE was 8.3±2.8 METs. Receiver operating characteristic curve identified that METs &lt;8.5 best predicts the combined outcome. As such, patients were classified into 260 with METs ≥ 8.5 and 323 with METs &lt; 8.5. Patients with METs &lt; 8.5 were older, had worse risk profiles, poorer resting and post-exercise diastolic variables, more Ex-DD (32% vs. 19%, p&lt;0.001), and more outcomes (55 [17%] vs. 22 [9%], p=0.002) compared to METs ≥ 8.5. Both Ex-DD (HR: 1.9, 95% CI: 1.2-2.9) and METs &lt; 8.5 (HR: 1.9, 95% CI: 1.1-3.1) independently predicted the combined outcome. The presence of both METs &lt; 8.5 and Ex-DD conferred the highest risk (HR: 2.9, 95% CI: 1.5-5.6) and remained significant after adjustment and propensity score matching, while the presence of either alone carried an intermediate risk (HR: 1.9, 95% CI: 1.1-3.5), which became non-significant after adjustment and matching. Conclusions: poor exercise capacity is associated with an adverse prognosis, irrespective of resting or Ex-DD. METs &lt; 8.5 had particularly poor prognosis when combined with Ex-DD, while either alone did not predict outcomes.
Abstract 14462: Baseline Characteristics of Tirzepatide-Treated Participants Who Shifted to a Normal Body Mass Index (&lt;25 kg/m <sup>2</sup> ): A Post Hoc Analysis From SURMOUNT-1
Authors: Reshmi Srinath, Naveed Sattar, Xuanyao He, Arian Plat, Beverly L Falcon, Adam Stefanski, Clare J Lee
Journal: Circulation (2023)

Introduction: Tirzepatide is a once weekly GIP and GLP-1 receptor agonist approved for the treatment of type 2 diabetes and under investigation for chronic weight management. In SURMOUNT-1, tirzepatide treatment resulted in substantial body weight reductions in people with obesity (body mass index (BMI) ≥30 kg/m 2 ) or overweight (BMI ≥27 kg/m 2 ). Hypothesis: This post hoc analysis assessed the baseline characteristics of tirzepatide-treated participants who reached normal BMI, defined by &lt;25 kg/m 2 . Methods: Participants (N=1834) from SURMOUNT-1 with at least one post-baseline BMI measurements and adherent to tirzepatide (≥75% of doses received) were included in this analysis. The proportion of participants who shifted to a normal BMI was assessed during the study period. Baseline demographics and clinical characteristics were compared between participants who shifted to a normal BMI vs those who did not reach a normal BMI by week 72. Results: A total of 380 participants shifted to a normal BMI during the study period. Participants who shifted to a normal BMI were slightly older, more likely to be female, with shorter duration of obesity and lower baseline BMI (in particular a BMI ≥27 to &lt;30 kg/m 2 or ≥30 to &lt;35 kg/m 2 ), HbA1c, fasting glucose, fasting insulin, systolic blood pressure, ALT and eGFR vs those who did not reach a normal BMI (Table). Additionally, fewer had prediabetes and hypertension, and a greater proportion of participants had dyslipidemia in those who reached the normal BMI vs those who did not. Conclusions: In this post hoc analysis from SURMOUNT-1, approximately one in five participants with overweight or obesity receiving tirzepatide treatment reached the normal BMI (&lt;25 kg/m 2 ) by week 72. Participants who reached the normal BMI were older, more likely to be female and had several favorable characteristics at baseline including lower baseline BMI, HbA1c, blood pressure, ALT and eGFR compared to those who did not reach the normal BMI.