tbuckley/cabot-search huggingface dataset:
Abstract 15220: The Thermal Characteristics to Phrenic and Esophageal Injuries During Ablation of QDOTMICRO (50w-Qmode and 90w/4sec-Qmode+) vs 50w-TactiCath SE vs 50w-Thermocool Smart Touch: Findings From an <i>In-Vivo</i> Porcine Study
Authors: Naoto Otsuka, Yasuo Okumura, Koichi Nagashima, Sayaka Kurokawa, Ryuta Watanabe, wakamatsu yuji, Shu Hirata, Moyuru Hirata, Masanaru Sawada, Toshiko Nakai
Journal: Circulation (2023)

Introduction: Recently, there have been numerous strategies for treating atrial fibrillation, including the choice of catheters However, the thermal characteristics of each catheter, particularly in terms of safety, have not been fully understood. Hypothesis: Our aim was to characterize the thermal damage to collateral tissues during 50W-HPSD ablation and 90W/4sec-vHPSD ablation using three different ablation catheters. Methods: In 28 pigs, we implanted thermocouples on the superior vena cava, close to the phrenic nerve, and on the esophageal, close to the inferior vena cava. We performed endocardial ablation near the fiducial markers of the thermocouples using three different RF catheters: ablation index (AI)-guided HPSD (Qmode) and vHPSD ablation (Qmode+) with QDOTMICRO, lesion size index-guided HPSD ablation (targeting 5.0) with TactiCath Sensor Enabled (Tacti), and AI-guided HPSD ablation (targeting 400) with Thermocool Smart Touch (STSF). We measured tissue temperatures during ablation, including maximum tissue temperature (Tmax), time to maximum tissue temperature (t-Tmax), time to achieve a lethal temperature of 50°C (t-50°C), and time to return to baseline from Tmax (t-Tbase). Results: In terms of the frequency of esophageal injury, there were no significant differences among the different catheters. However, the depth of esophageal injury from the adventitia showed a significant difference. In terms of phrenic nerve injury, Tacti had the highest frequency compared to the other catheters (100%, p=0.0012). Tmax, t-Tmax, t-50°C, and t-Tbase showed significant differences, as shown in figure. Conclusions: The thermal effects on collateral tissues differ among the three different catheters and settings. STSF and Qmode result in a gradual increase in tissue temperature, while Tacti and Qmode+ lead to a rapid temperature increase. These distinct thermal distributions may contribute to the risk of phrenic nerve and esophageal injuries.
Abstract 14810: ASCVD Risk Score vs Machine Learning-Based Algorithm in the Prediction of ASCVD Events in Women With Breast Cancer
Authors: Nickolas Stabellini, Roger S Blumenthal, Marcio S Bittencourt, Seamus P Whelton, Darryl Leong, Justin Moore, Jennifer Cullen, Priyanshu Nain, John Shanahan, Susan F Dent, Alberto Montero, Avirup Guha
Journal: Circulation (2023)

Introduction: Cancer patients may face an elevated risk of developing atherosclerotic cardiovascular disease (ASCVD). Consequently, a conventional pooled cohort equation may not accurately predict cardiovascular (CV) outcomes in this population. Hypothesis: A cancer-specific algorithm is superior to conventional ASCVD risk scores in women with breast cancer (BC). Methods: Women ≥18 years, diagnosed with BC between 2005-2012 at a hybrid academic-community practice (Northeast Ohio, US) were included. A Machine Learning (ML) XGBoost algorithm (with survival modelling), developed using a training subset of the cohort (60% train + 20% test), ranked 40 covariates (including demographic, treatment-related and social determinants of health information) for ASCVD prediction using SHAP (SHapley Additive exPlanations) values. The top 10 ML predictors were transformed in a predictive equation using logistic regression models. This equation was tested in the cohort validation subset (20%), and subsequently compared to the ACC/AHA ASCVD risk score via time-dependent receiver operating characteristic curve. Results: BC women (n=5,687, Table 1) had a median age of 60 (interquartile range 50-71) years, 17% had advanced stage disease (TNM III-IV), 44.2% received chemotherapy, 60% endocrine therapy, 29.2% radiotherapy, and 73.3% surgery, respectively. Of those, 16.7% had a 10-year ASCVD. The ACC/AHA risk score had an area under the curve (AUC)=0.76 and underestimated ASCVD in 4.9% (mean risk=21.3% [95% CI 19.9-22.6] vs. mean predicted risk=16.4% [95% CI 15.2-17.5]). The equation pooled from the top-10 predictors of the ML algorithm (C-index=0.81 [95%CI 0.80-0.82]) achieved an AUC=0.84. Conclusion: Conventional ASCVD risk scores tend to underestimate the risk in women with BC. A cancer-specific model exhibited excellent performance and generated a user-friendly equation for predicting ASCVD risk in this population. Further external validation is needed.
Abstract 15552: Augmentation of Right Ventricular Strain Dynamics During Direct Mechanical Ventricular Actuation
Authors: Benjamin A Schmitt, Yirong Zhou, Mark P Anstadt
Journal: Circulation (2023)

Introduction: Available forms of mechanical circulatory support are associated with significant complications related to blood contact. Direct cardiac compression (DCC) devices avoid blood contact but may impair diastolic function. This derogatory effect of DCC devices may be related to a negative impact on RV function. Direct mechanical ventricular actuation (DMVA) uniquely augments LV diastolic function. The purpose of this study was to evaluate DMVA’s effect on RV function. Methods: Ischemic heart failure (HF) was induced using 5 mins of ventricular fibrillation (VF) circulatory arrest in large mature canines (n=9). Hearts were defibrillated and DMVA applied for 15 mins. VF circulatory arrest was subsequently re-induced for 5 mins to generate progressive HF. The experimental protocol was continued for 3 hrs. Intracardiac echocardiography was used to quantify longitudinal strain and peak strain rates in the RV and LV using speckle-tracking algorithms. Two-way ANOVA with Tukey HSD tests were used to evaluate statistical differences in strain metrics (baseline vs. HF vs. DMVA support and LV vs. RV). Results: DMVA increased RV fractional area change (DMVA: 0.282 ± 0.011, Mean ± SEM) relative to either baseline (0.221 ± 0.15, p=0.004) or HF (0.170 ± 0.006, p&lt;0.001). DMVA statistically significantly augmented all RV strain metrics relative to either baseline or HF (Table). Additionally, all DMVA strain metrics were statistically significantly greater in the RV than the LV (LV strain: 18.8 ± 0.5 %, p&lt;0.001, LV strain rate: systolic, -1.46 ± 0.04 1/s, p&lt;0.001, diastolic, 1.51 ± 0.04 1/s, p&lt;0.001). Conclusions: DMVA substantially improved RV strain dynamics compared to baseline or HF in this model. During DMVA support, strain dynamics in the RV were amplified more than the LV. This RV augmentation is important to achieving balanced biventricular DMVA support. Enhanced diastolic RV and LV augmentation during DMVA remains highly unique when compared to any other devices.
Abstract 12887: Cyclin D2 Overexpressing and Hypoimmunogenic Cardiomyocyte Spheroid Transplantation Induced Endogenous Myocardial Regeneration in the Pig Heart After Myocardial Infarction
Authors: Yuhua Wei, Greg Walcott, Thanh Nguyen, Xiaoxiao Geng, Bijay Guragain, Hanyu Zhang, Akazha Green, Jack Rogers, Lei Ye, Jianyi J Zhang
Journal: Circulation (2023)

Background: hiPSCs derived cardiomyocytes (hiPSC-CMs) have very low proliferative capacity, while patient hiPSC-CMs may have disease phenotypes which compromise therapeutic efficacy and allogenic hiPSC-CMs are expected to induce an immune response during clinical use. In order to solve these problems, we established a hiPSC line by knocking-out two components of the human leukocyte antigen (HLA) and over-expressing myosin heavy chain driven cyclin D2 (CCND2) systems in hiPSCs ( HLA-KO/CCND2-OE hiPSCs). Aim: To determine the therapeutic efficacy and mechanism of the xeno-transplantation of HLA-KO/CCND2-OE hiPSCs derived cardiomyocytes ( HLA-KO/CCND2-OE hiPSC-CMs) in the pig hearts after myocardial ischemia/reperfusion (IR). Methods and Results: HLA-KO/CCND2-OE hiPSC-CM spheroids were differentiated in shaking flasks. Purified HLA-KO/CCND2-OE hiPSC-CM spheroids were intramyocardially injected into pig hearts after IR (the Spheroid Group), while control animals received basal medium injection (the IR Group). Cardiac magnetic resonance imaging (cMRI) showed that pig heart function improved significantly compared to the IR Group at 4 weeks after IR. This finding was associated with a dramatical reduction in the scar size as determined by late gadolinium enhancement measurement. Immunohistology showed that significantly increased porcine CMs expressed cell proliferation markers, such as Ki67, phospho-histone 3 (pH3), and symmetrical Aurora B, and abundant YAP protein expression in porcine CM nuclei in the porcine hearts of the Spheroid Group compared to the IR Group at 1 week after IR. Western Blot analysis of pig heart tissue showed significantly reduced expression of phospho-YAP in the Spheroid Group. snRNAseq showed that number of cycling porcine CMs was &gt; 5 folds in the Spheroid Groups than that in the IR Group. Angiogenic microarray showed that HLA-KO/CCND2-OE hiPSC-CM spheroids produced abundant follistatin which induced YAP protein expression and cytokinesis in CMs. Conclusions: Transplantation of HLA-KO/CCND2-OE hiPSC-CM spheroids effectively recovered porcine heart function, reduced scar size, and induced porcine CM proliferation through modulating YAP protein expression by follistatin secreted by transplanted cells.
Abstract 180: Brain Tissue Metabolomics Study Supports the Use of Multi-Drug Cocktail Approach for Neuroprotection After Asphyxial Cardiac Arrest in Rats
Authors: Rishabh C Choudhary, Muhammad Shoaib, Tai Yin, Kei Hayashida, Cyrus Kuschner, Mingzhu He, Yousef Al-Abed, Junhwan Kim, Lance B Becker
Journal: Circulation (2023)

Background: We have recently shown that using a multi-drug cocktail therapy targeting multiple pathways simultaneously could be a novel therapeutic approach to reduce ischemic brain injury following asphyxial cardiac arrest (CA) and resuscitation. To further validate the affected pathways using a multi-drug cocktail, we aimed to investigate changes in brain tissue metabolites after asphyxial CA and cardiopulmonary resuscitation (CPR) in rats. Methods: The multi-drug cocktail formulation included ten neuroprotective drugs (CoQ10, Cyclosporin A, Edaravone, Metformin, N- acetylcysteine, Poloxamer 188, SS-31, Sulbutiamine, Vitamin C, and Zoniporide) focusing on distinct metabolic pathways of ischemia-reperfusion injury. Male Sprague-Dawley rats underwent 12 min of asphyxial-CA followed by CPR and received either a multi-drug cocktail or a vehicle (n=6) immediately after resuscitation. At 2 hr post-resuscitation rats were euthanized, and the whole-brain tissue was processed for mass spectrometry for metabolomic analysis. Data were collected both in +ve and -ve ion modes and the collected data were analyzed using metaboanalyst 5.0. Results: A total of 139 metabolites were detected in +ve ion mode whereas 132 metabolites were detected in -ve ion mode. While combining and removing a duplicate number of metabolites a total of 234 metabolites were analyzed. Our principal component analysis (PCA) data showed a shift of overall metabolites towards sham groups with multi-drug cocktail treatment after 12 min CA. Out of 234 metabolites 40 were significantly increased and 19 were significantly decreased between cocktail and vehicle-treated groups (Suggested by Volcano Plot, p=0.05, fold Change =1). A total of 15 pathways were significantly impacted between cocktail and vehicle-treated groups (p= 0.05) suggesting the broad effect of a multi-drug cocktail therapy after asphyxial CA and resuscitation Conclusion: This study represents an innovative attempt that employs metabolomics research to elucidate the effects of a multi-drug cocktail in a severe CA rodent model, uncovering a notable alteration in the overall metabolic profile of the brain and suggesting an important role of multi-drug cocktails in ischemic injury.
Abstract 16010: Sudden Death in the Systemic Right Ventricle: Single Center Study of Dextro-Transposition of the Great Arteries Palliated With Atrial Switch
Authors: Rimsha Ahmad, Anca Chiriac, Jaideep Singh Bhalla, Ramila Mehta, Heidi M Connolly, Alexander C Egbe, Duy Nguyen, Christopher J McLeod, Samuel Asirvatham, Malini Madhavan
Journal: Circulation (2023)

Introduction: The incidence and risk factors for sudden cardiac death (SCD) in patients with systemic right ventricle (sRV) and D-TGA palliated with atrial switch procedures is not well understood. Methods: This cohort was examined retrospectively for the composite end point of SCD, sustained ventricular tachycardia (VT) &gt;30 s or appropriate ICD therapy for VT. Clinical characteristics of those with and without the end point were compared using the Kruskal-Wallis or Chi-square test as appropriate. Results: The composite end point occurred in 15 of 148 (10%) patients (63.5% male) at a mean age of 36.4 (SD 10.3) years. SCD occurred in 6 patients (n=2 successfully resuscitated), sustained VT in 6 patients and ICD therapy for VT in 3 patients who had previously received a primary prevention ICD. Patients with SCD/VT had lower sRV ejection fraction (EF) compared to patients without SCD/VT [28±11 vs 40±10%, P&lt;0.001]. The odds ratio of SCD/VT in patients with sRVEF≤35% compared to sRVEF&gt;35% was 13.3 (95% CI 2.8 - 64.4). Kaplan Meier analysis of time to SCD/VT stratified by sRV EF is presented in figure. QRS duration, QRS fragmentation, QTc and history of systemic AV valve surgery were not significantly associated with SCD/VT. Non-sustained ventricular tachycardia (NSVT) on Holter monitoring occurred more frequently in SCD/VT patients (80 vs 39%, p=0.003). All 11 survivors of SCD/VT received an ICD; appropriate ICD therapy occurred in 27% of these patients during follow-up. Conclusion: SCD or VT occurred in one-tenth of D-TGA patients palliated with atrial switch, predominantly in 3 rd and 4 th decade of life. Reduced sRV EF was the most important association and ICD implantation for primary prevention of SCD is a reasonable consideration in those with reduced sRV EF.
Abstract 13563: Long-Term Prognostic Value of Afterload Mismatch Index in Acute Decompensated Heart Failure With and Without Reduced Left Ventricular Ejection Fraction
Authors: Takahisa Yamada, Tetsuya Watanabe, Takashi Morita, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Tsutomu Kawai, Yuji Nishimoto, Masahiro Seo, Jun Nakamura, Takeshi Fujita, Masanao Taniichi, Yongchol Chang, Masatake Fukunami
Journal: Circulation (2023)

Backgrounds: Ventricular-arterial coupling has been shown to have physiologic importance in heart failure. At the acute worsening of heart failure, increased ratio of pulmonary capillary wedge pressure to systemic systolic pressure (PCWP/SBP) might reflect the degree of afterload mismatch. However, there is no information available on the long-term prognostic value of PCWP/SBP in patients with acute decompensated heart failure (ADHF), relating to reduced left ventricular ejection fraction (LVEF). Methods: We studied 240 patients admitted for ADHF (with LVEF&lt;40% [HFrEF, n=110] and without LVEF&lt;40% [n=130]), who underwent right heart catheterization at the admission and were discharged with survival. PCWP/SBP was obtained at the admission. The study endpoint was cardiovascular death (CVD). Results: During a mean follow-up period of 5.2±4.4 yrs, 59 patients had CVD. PCWP/SBP was significantly higher in patients with than without CVD (0.216±0.078 vs 0.172±0.064, p&lt;0.0001). Multivariate Cox regression analysis revealed that PCWP/SBP was significantly associated with CVD, independently of prior heart failure hospitalization, body mass index, estimated glomerular filtration rate, and serum sodium level. Patients with high PCWP/SBP (&gt;0.206 determined by ROC analysis: AUC 0.668[0.586-0.749]) had a significantly greater CVD risk than those with low PCWP/SBP (≤0.206) in both groups with and without HFrEF(with: 36% vs 11%, p=0.016; without: 42% vs 18%, p=0.0057). Conclusions: PCWP/SBP, an index of afterload mismatch, could provide the long-term prognostic information in patients admitted with ADHF, regardless of reduced LVEF.
Abstract 13679: Personalized Guidance of Edge-to-Edge Transcatheter Tricuspid Valve Repair
Authors: Alexandru Patrascu, Ilka Ott
Journal: Circulation (2023)

Introduction: Transcatheter edge-to-edge tricuspid valve repair (T-TEER) for tricuspid regurgitation (TR) is always guided by TEE. Hypothesis: Safety and efficacy of T-TEER can be increased by multimodality imaging (MMI) guidance. Methods: From December 2020 to January 2022, we performed T-TEER in 40 inoperable patients. All patients received TTE, TEE and cardiac CT screening, and were assigned to a MMI (n=17) guidance group, provided good TTE acoustic window, or otherwise classical TEE (n=23). Multimodality imaging employed the 4 right-sided chamber views. Accordingly, the 1-chamber view was obtained in the transgastric short-axis view on TEE, but also from a modified subcostal TTE short axis. The 2-chamber view was visualized from a low-esophageal position, or from a parasternal long axis view of the right ventricle. The 3-chamber view was seen on mid-esophageal TEE 50-100°, but also in the parasternal short axis view. Finally, the 4-chamber view was obtained on mid-esophageal 0-30°, or the classical four-chamber TTE view. CT derived fluoroscopic angulations of these views allowed interventionalists and imaging specialists to speak a common language. Results: Device success was achieved in all patients, with 1.5±0.6 implanted clips / patient in the MMI vs 1.5±0.5 in the TEE group (p=0.851). Device times were 66.1±35.1 vs 58.7±27.5 minutes (p=0.459). TR reduction was successful in 94% vs 95% of patients, p=1.000. Two- or more grade TR improvement occurred in 65% vs 52% of cases. There were no device associated complications but 3 TEE-related gastro-esophageal bleedings occurred in the 2 nd group. By 12 months, 4 vs 8 patients (p=0.504) were readmitted for acute heart failure, and 2 vs 4 (p=0.686) died. NYHA class decreased by one grade in all survivals. However, Kansas City Cardiomyopathy Questionnaire score and 6-minute walk distance significantly increased in each respective group, more with MMI ( Δ 29±21.4 vs 22±13.6 points, p=0.227; Δ 101±100.4 vs 85±64 meters, p=0.121). Conclusions: A patient-tailored MMI approach to T-TEER guidance, by using TTE in patients with good acoustic window and cardiac CT for fluoroscopic determination of the 4 right-sided chamber views, is feasible and improves safety, procedural success and, in turn, clinical outcomes.
Abstract 18236: Enhancing Predictive Accuracy of H2FPEF Score in Suspected HFpEF by Incorporating Left Atrial Reservoir Strain
Authors: Mariane Shinzato, Natasha Santos, Renato Cancellier, Gustavo Nishida, Henrique Takachi Moriya, Yuri Maduro, Jorge Assef, Roberto Botelho, Carlos Hossri, Fausto Feres, Kleber Franchini, Renato Hortegal
Journal: Circulation (2023)

Introduction: Diagnosing HFpEF can be challenging, but the H 2 FPEF score is a valuable tool for clinical decision-making. Atrial fibrillation (AF) plays a significant role in this score, creating challenges for diagnosis in patients without AF or with paroxysmal AF. Left atrial reservoir strain (LArS) has emerged as a promising indicator for both AF and HFpEF. This study explores how incorporating LArS can enhance the predictive ability of the H 2 FPEF score for exercise capacity in outpatients with suspected HFpEF. Methods: This cross-sectional study has a sample size of 283 patients with suspected HFpEF. We collected clinical and echocardiographic data and compared LArS values across different H 2 FPEF score categories. Additionally, we analyzed a subgroup of 129 patients who underwent a Cardiopulmonary Exercise Test (CPET) to evaluate the effectiveness of the H 2 FPEF score and LArS in predicting Peak VO 2 . To further comprehend the contribution of each feature in the performance of the H 2 FPEF score, we used Shapley Additive Explanations (SHAP) analysis. Results: Most patients were female (63%), age of 60 (±12) years and LVEF of 60 (±5.2)%. Patients with low scores had a LArS of 32.6 (± 6.8)%, while those with moderate and high scores had probabilities of 26(± 8.2)% and 16 (±8.2)%, respectively (p&lt;0.001). The H 2 FPEF score demonstrated an AUC of 0.74 (95% CI: 0.64-0.84) in predicting peak VO 2 , whereas LArS exhibited an AUC of 0.71 (95% CI: 0.62-0.80). Incorporating LArS into the score improved its performance, resulting in an AUC of 0.82 (95% CI: 0.75-0.89). The SHAP analysis revealed that LArS had a significant impact as the most important feature (Figure 1), while the importance of the atrial fibrillation criterion decreased significantly. Conclusions: Our findings show that integrating LArS improves the diagnostic performance of the H 2 FPEF score and offers a valuable alternative to the AF criterion within the H 2 FPEF algorithm.
Abstract 17706: Role of p62/SQSTM1 on Acute Ischemia-Induced Arrhythmias After Chronic Smoke in Mice
Authors: Hyun Seok Hwang, Ann Centner, Vladimir Ukhanov, Joanne Zhao, Alexis Cejas Carbonell, Isela Valera, Michelle Parvatiyar, Gloria Salazar
Journal: Circulation (2023)

Introduction: Cigarette smoke presents a high-risk factor for coronary heart disease development. Cigarette smoke is often linked with increased susceptibility to cardiac ischemia and arrhythmias. p62/SQSTM1 is a stress-sensing protein responsible for proteasomal degradation that maintains redox homeostasis during cardiac tissue injury. However, its exact mechanism for arrhythmia development is not clear. Hypothesis: Here we tested the biological role of p62/SQSTM1 mice on cardiac ischemia injury-induced arrhythmogenesis after chronic cigarette smoke exposure. Methods: Mice (global p62/SQSTM1 deletion mice; p62/SQSTM1 -/- , 4 months old age) were exposed to cigarette smoke (9.4 mg tar/0.726 mg nicotine) for 16 weeks. Afterward, we utilized ischemia-reperfusion (IR) injury in intact hearts to test the risk of arrhythmias. Results: The smoke-exposed p62/SQSTM1 -/- isolated hearts (8 months old age) significantly reduced the incidence of ventricular arrhythmias compared to hearts obtained from p62/SQSTM1 +/+ mice post-IR during the first 15 minutes reperfusion (% of mice with ventricular arrhythmias, p62/SQSTM1 +/+ ; 7/10 hearts, p62/SQSTM1 -/- ; 2/8 hearts*, * &lt;0.05). Abnormal Ca 2+ regulation in cardiomyocytes is triggering diastolic delayed afterdepolarizations and often leads to ventricular tachycardia. Therefore, we tested cellular Ca 2+ regulation with acute cigarette smoke extract (CSE) exposures in cardiomyocytes. p62/SQSTM1 -/- cardiomyocytes for 30 minutes exposed to CSE significantly alleviated CSE-induced spontaneous Ca 2+ waves (% of cardiomyocytes with spontaneous Ca 2+ waves, p62/SQSTM1 +/+ ; 6/13 cells, p62SQSTM1 -/- ; 1/15 cells*, * &lt;0.05). Conclusions: Overall, our results suggest that the deletion of p62/SQSTM1 protein has a protective effect on acute cardiac ischemia-induced arrhythmogenesis after chronic cigarette smoke in mice.