tbuckley/cabot-search huggingface dataset:
Abstract 17537: Myocardial Dysfunction is Associated With Impaired Angiogenesis in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Sabina Frljak, Gregor Poglajen, Gregor Zemljic, Andraz Cerar, Bojan Vrtovec
Journal: Circulation (2023)

Background: Recent evidence suggests that myocardial microvascular damage may represent a key parameter in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Aim: We sought to investigate a potential correlation between parameters of angiogenesis and myocardial dysfunction in HFpEF patients. Methods: We enrolled 30 consecutive HFpEF patients with NYHA class III, left ventricular ejection fraction (LVEF) &gt;50%, E/e' &gt;15, and NT-proBNP &gt;300 pg/ml. In all patients endothelial progenitor cells (EPCs) were mobilized by granulocyte-colony stimulating factor (G-CSF; 10 mcg/kg, 5 days) and collected via apheresis. Before EPC mobilisation we performed echocardiography and measured plasma levels of biomarkers of angiogenesis. All patients underwent electroanatomical mapping for the measurement of myocardial viability; preserved viability was defined as mean unipolar voltage&gt; 8.3 mV. Results: Myocardial viability was preserved in 11 patients (37%; Group A) and decreased in 19 patients (63%; Group B). The groups did not differ in age (63±10 years in Group A vs. 61±8 years in Group B, P=0.78), gender (male: 73% vs. 79%, P=0.70), serum creatinine (1.07±0.34 mg/dL vs. 1.04±0.40 mg/dL, P=0.43), or LVEF (60±7% vs. 57±4%, P=0.32). In Group B we found higher levels of NT-proBNP (2370±1020 pg/mL vs. 920±455 pg/mL in Group A, P=0.04) and E/e’ (23.2±3.1 vs. 17.4±1.8 pg/ in Group A, P=0.02). After G-CSF stimulation, we found significantly lower numbers of EPCs in Group B (53±42 x10 6 cells/L) than in Group A (102±52 x10 6 cells/L, P=0.001). Similarly, apheresis yielded lower numbers of EPCs in Group B (85±82 x10 6 cells vs. 200±93 x10 6 cells in Group A, P=0.003). When compared to Group A, patients in Group B displayed lower levels of pro-angiogenic biomarkers (agiopoietin-1: 7.4±2.8 ng/mL vs. 12.4±5.1 ng/mL, P=0.02; vascular endothelial growth factor: 27.5±20.1 pg/mL vs. 51.6±24.2 pg/mL, P=0.01), and higher levels of anti-angiogenic biomarkers (endostatin: 56.5±19.1 ng/mL vs. 33.2±14.3 ng/mL, P=0.01; thrombospondin-2: 16.4±4.3 ng/mL vs. 9.2±5.0 ng/mL, P=0.03). Conclusion: In patients with HFpEF, myocardial dysfunction appears to correlate with reduced mobilisation of endothelial progenitor cells and impaired angiogenesis.
Abstract 14835: A Rare Case of Left Atrial Thrombus Post Extensive Ablation Despite Therapeutic Anticoagulation
Authors: Shahmir Naveed, Samir P Mehta, Abdul Azizi, Avinash Chandra
Journal: Circulation (2023)

Introduction: Persistent Atrial Fibrillation (AF) is often treated with radiofrequency catheter ablations to the pulmonary veins as well as linear ablations of the left atrium. Extensive ablations can increase the risk of clotting at the ablation site. Case: A 47-year-old male with a history of Shone Syndrome, AF on Warfarin with prior ablations presented for acute monocular vision loss found to be due to central retinal artery occlusion. Symptoms were three weeks after repeat PVI and posterior wall isolation. Transesophageal echocardiogram (TEE) showed multiple mobile echodensities suspicious for thrombi in the left atrium but no LAA thrombus. With elevation of INR goal range to 3 to 3.5 and addition of aspirin there was resolution of the left atrial thrombi on repeat TEE 2 months later. Discussion: Visual loss was suspected to be cardioembolic. The cause of thrombi, despite being anticoagulated with an INR of 2.6, was multifactorial from chronic fibrosis, repeated ablation-induced injury yielding endothelial damage, elevated LA pressures due to mitral stenosis, and persistent atrial flutter. Multiple small thrombi visualized adherent to left atrial wall without any thrombus in LAA. Advanced imaging cannot guide anticoagulation strategy directly but can assess fibrotic burden. It is important to consider increasing the INR goal or adding aspirin to high-risk patients. Conclusion: Patients should be risk stratified when extensively ablated and with elevated atrial pressures with multimodal imaging to determine risk and management when undergoing extensive ablation. Further investigation needs to be done to determine if heightened anticoagulation goals are needed based on risk stratification.
Abstract 12793: Atrial Arrhythmias in the Young and Syncope: Insights From the Nationwide Readmissions Database
Authors: Supreet Singh, Saloni Agrawal, William Whang
Journal: Circulation (2023)

Introduction: Atrial fibrillation and atrial flutter are two of the most common cardiac arrhythmias in the general population, and have been recognized in patients who present with syncope. Atrial arrhythmias could be a marker for autonomic dysfunction, especially in the younger population. Large database studies investigating the impact of atrial fibrillation and atrial flutter on patients with syncope are lacking. This study aims to utilize the Nationwide Readmissions Database (NRD) to analyze patients admitted with syncope and to compare readmission rates among those with versus without atrial arrhythmias. Methods: We queried the 2018 NRD for admissions with a primary diagnosis of syncope in patients aged 18 or older. Admissions were grouped into two cohorts: the atrial fibrillation/atrial flutter (AFF) cohort and the non-AFF cohort. Propensity score matching was used to balance the two groups. The cohorts were analyzed over a 6-month follow-up period using readmission for syncope as the primary outcome. A multivariate cox-regression model was utilized to examine the association between atrial arrhythmias and readmission for syncope. Results: 7,986 non-AFF index admissions were matched to 8,046 AFF index admissions. Overall, readmission rates between non-AFF and AFF cohorts were similar (2.2% vs 2.1%, p = 0.75), however, young patients (60 or younger) in the AFF cohort had a higher readmission rate than young patients in the non-AFF cohort (6.4% vs 3.2%, p = 0.04). There was a statistically significant interaction between age and atrial arrhythmias; patients aged 60 or younger with atrial arrhythmias were twice as likely to be readmitted for syncope over the 6-month follow-up period (HR: 2.09 (1.07 - 4.09), p = 0.03). Conclusions: Increased risk of re-admission for syncope in the younger population with AFF could be an indicator of autonomic dysfunction and warrants further exploration for potential treatments that address this common mechanism.
Abstract 14798: NAMPT Inhibition Restores Coronary Microvascular Dysfunction in Diabetes
Authors: Francisco J Ramirez, Lei Gao, Jody Cabrera, Rahatullah Razan, Mingya Yang, Joe G Garcia, Ayako Makino
Journal: Circulation (2023)

Introduction: Nicotinamide phosphoribosyltransferase (NAMPT) is a multitask peptide; extracellular NAMPT acts as a proinflammatory cytokine, and intracellular NAMPT participates in energy metabolism through NAD + production. Serum NAMPT level is increased in diabetic patients; however, the pathophysiological role of NAMPT in diabetic cardiovascular complications is poorly understood. This study aims to investigate the effect of NAMPT inhibition on coronary microvascular function in diabetes. Materials and Methods: We used two diabetic mouse models: inducible type 2 diabetic (T2D) mice generated by a single injection of low-dose STZ (75 mg/kg, i.p.) with a high-fat diet feeding, and spontaneous T2D mice, TALLYHO/JngJ. Cardiac endothelial cells (CECs) were isolated for molecular biological experiments. Coronary flow velocity reserve (CFVR) was used to determine coronary microvascular function. Results: T2D mice exhibited elevated NAMPT expression in CECs. There was no difference in glucose tolerance and body weight in diabetic NAMPT hetero knockout mice and FK866 (NAMPT inhibitor)-administered diabetic mice compared to their controls. However, CFVR was significantly increased by NAMPT inhibition in T2D mice, accompanied by increased capillary density and augmented endothelium-dependent relaxation (EDR). Chronic administration of neutralizing NAMPT antibody (Ab) also improved CFVR in T2D mice toward the level in control mice. RNA sequencing data in CECs revealed that NAMPT-Ab administration in T2D mice significantly restored the levels of genes related to angiogenesis. NAMPT (100 ng/ml) or NAD + (100 nM) treatment attenuated cell migration in control CECs and reduced EDR in control CAs. Furthermore, NAMPT or NAD + treatment increased mitochondrial ROS formation and decreased Gap junction activity in control CECs. Conclusion: Our data suggest that NAMPT inhibition increases capillary density via enhancing endothelial migration, arguments EDR through reducing mitochondrial ROS production and increasing gap junction activity, and results in restoration of coronary microvascular function in diabetic mice. Therefore, NAMPT inhibition could be a new therapeutic strategy for coronary microvascular disease in diabetes.
Abstract 16405: Perm1 Protects the Heart From Pressure Overload-Induced Dysfunction by Promoting Oxidative Metabolism
Authors: Shizuko Tachibana, Nam-Kyung Yu, Carolina Fernandez-Costa, Ruixia Li, Alex Liang, Janet Choi, Dayoen Jung, Anastasia Kralli, Changchun Xiao, John Yates, Robert S Ross, Yoshitake Cho
Journal: Circulation (2023)

Introduction: Defects in ATP production lead to cardiac dysfunction and heart failure (HF) while restoring reduced mitochondrial (Mito) function mitigates HF. Previously we showed that a novel Mito protein, Perm1 (PGC-1 and ERR-induced regulator, muscle 1), promotes Mito biogenesis in cardiomyocytes (CM). Here we studied the role of myocardial Perm1 in vivo . Hypothesis: Perm1 protects the heart from pressure overload-induced dysfunction. Methods: First, we generated cardiac-specific Perm1 transgenic mice (Perm1cTG). Next, we induced pressure overload by transverse aortic constriction (TAC) or performed Sham operations on 10-week-old control (CTL) and Perm1cTG male mice. Heart function, histology, and biochemical analyses were performed eight weeks postoperatively. To understand the mechanism of Perm1, the heart protein samples were subjected to quantitative mass spectrometry (MS) analysis, and we also identified Perm1 binding proteins in the heart by MS. Finally, mouse neonatal CM were infected with adenoviruses expressing shMic60 (knock down) or shControl in combination with Perm1 or LacZ, followed by oxygen consumption rate (OCR) analysis. Results: Sham-operated Perm1cTG and CTL mice showed no differences in function and morphology. Following TAC, CTL developed severely reduced heart function, while Perm1cTG had only minimal change. Perm1cTG TAC mice also showed reduced cardiac hypertrophy, Anf and Bnp mRNA expression, and fibrosis, compared to CTL TAC, showing Perm1 protects the heart from hemodynamic stress. Perm1cTG TAC hearts showed significantly increased OCR compared to CTL TAC, suggesting Perm1 preserves TAC-induced CM Mito dysfunction. MS analysis identified MICOS (mitochondrial contact site and cristae organizing system) and oxidative phosphorylation proteins were upregulated in Perm1cTG TAC hearts compared to CTL TAC. Moreover, we found that Perm1 binds to Mic60, which is a core component of the MICOS. Finally, Mic60 was required for Perm1-induced maximal oxidative capacity, suggesting Perm1 acts through Mic60. Conclusion: Perm1 protects the heart against pressure overload by restoring oxidative metabolism. Future studies will reveal the role of Perm1/Mic60 in the heart. This work is supported by NIH R01HL151239.
Abstract 17795: Increased Long-Term Odds of Atrial Fibrillation in Overweight or Obese Young Men: A Systematic Review and Meta-Analysis
Authors: Preet Doshi, Santiago Saenz Ancira, Yash Patel, Javier Higuera Ornelas, Sunitha Geddada, Sricharan Chiluveru, Sandhya Shanthosh kumar, Chenna reddy Tera, Vardhan Chalasani, Prerna Bansal, Harika Varma Chintalapalli Patta, Ankit Vyas, Rupak Desai
Journal: Circulation (2023)

Aim: Studies in the past have linked obesity as a risk factor for atrial fibrillation (AF). However, there is a paucity of data on this influence in young adult males. This meta-analysis aims to evaluate and stratify the association between BMI and AF among young men. Methods: PubMed, Scopus, and Google Scholar databases were systematically reviewed for studies reporting long term-incidence of atrial fibrillation in young male adults (18-49 years) with obesity (BMI&gt;30 kg/m 2 ), and overweight BMI (BMI 20-25 kg/m 2 ). Random effects models were used for the meta-analyses and subgroup analyses. I 2 statistics were used to identify (&gt;50%) heterogeneity. A sensitivity analysis was performed using leave-one-out method. Results: Six studies with a total of 21,856,538 individuals were screened, out of which 6,732,531 young males with higher BMI and obesity were evaluated for the risk of Atrial fibrillation for a median follow-up duration of 6.3 years (3.3 - 29 years range). South Korean and Japanese studies together constituted 99.86% of the study population. Most commonly associated comorbidities were hypertension, diabetes mellitus type 2, dyslipidemia and smoking. The unadjusted HR showed a significant association between overweight (BMI 25-30) [OR:1.42, (95%CI:1.28-1.58, I 2 : 75.86%; p&lt; 0.01] and obesity (BMI &gt;30) and AF [OR: 2.02, (95%CI: 1.77-2.29, I 2 :64.3%; p=0.02] in young adult males. After multivariable analysis, the association remained significant for overweight [OR:1.22, 95%CI: 1.14-1.32, I 2 : 82.74%; p&lt; 0.01] and obesity [OR:1.48, 95%CI: 1.29-1.71, I 2 : 90.43%; p&lt; 0.01]. Sensitivity analysis indicated that no single study unduly influenced the pooled estimates. Conclusion: This meta-analysis revealed that higher BMI (overweight and obese) in young males is associated with an increased long-term risk of AF over a median follow-up duration of 6.3 years.
Abstract 17420: Enhanced Identification of Cardiac Wall Motion Abnormalities: An Externally Validated Deep Neural Network Approach Outperforms Expert and Quantitative Analysis of Electrocardiograms
Authors: Albert J Rogers, neal bhatia, James Tooley, Vyom Thakkar, JUSTIN XU, Rayan Ansari, Jessica Torres, Jagteshwar Tung, Mahmood Alhusseini, Paul L Clopton, Reza Sameni, Gari Clifford, Euan A Ashley, Marco V Perez, Matei Zaharia, Sanjiv M Narayan
Journal: Circulation (2023)

Background: Cardiac wall motion abnormalities (WMA) independently predict mortality and other adverse events beyond ejection fraction. Clinical screening relies on detection of ECG Q waves yet has poor predictive accuracy. Hypothesis: We hypothesized that ECG features beyond the Q wave could be identified by deep learning to improve WMA detection over standard ECG measurements. Methods: We collected ECGs and echocardiogram pairs (Panel A) in 35,210 unique patients who underwent both studies within 60 days at Stanford University. WMAs were determined by natural language processing (NLP) of clinical reports (Panel B). Five second ECG signals were extracted digitally and used to develop and test a DNN. For development, 80% of the pairs were used and 20% (N = 7042) were reserved for internal validation. We then tested the model performance on 2,338 echo/ECG pairs from Emory University. For comparison, qualitative physician statements from the ECG interpretation suggesting myocardial injury, ischemia, or infarct were labeled using NLP, and a logistic regression model was developed to include quantitative Q-wave measurements. Results: In the internal validation cohort (62.9±16.9 years, 47% female, 58% white), DNN of the ECG detected echocardiographic WMA with a c-statistic of 0.781 (CI: 0.764-0.798) which was superior to quantitative ECG Q wave measurement (0.632, CI: 0.605-0.661) or qualitative interpretation (0.595) (Panel C). Performance was not improved by incorporating demographic data. In the external cohort (61.9±16.0 years, 48% female, 48% white), the DNN AUC was 0.723 (CI:0.689-0.758). Conclusion: Deep learning improves detection of cardiac WMAs from the electrocardiogram in an externally validated model compared with standard ECG analysis. Application of this model may provide improved screening for regional myocardial injury. Further work will determine which features beyond the Q wave provide improved performance.
Abstract 18886: Rare but Fatal: Thrombus Formation and Cerebral Infarction Following Atrial Fibrillation Ablation
Authors: Kunjan Udani, Ateet Kosaraju, Lakshmi Subramanian, Sashwath Srikanth, Sivakumar Ardhanari
Journal: Circulation (2023)

Introduction: Atrial fibrillation (AF) ablation has become increasingly common as a first line treatment for young, healthy patients and recurrent AF. While the procedures are effective and safe with a mortality rate of &lt;0.1%, it can be associated with fatal complications. Case Presentation: A 74-year-old male with a history of AF status post epicardial ablation, ascending and thoracic aortic aneurysm, hypertension, dilated cardiomyopathy, sick sinus syndrome and alcohol use presented with left hemiparesis and left sided facial droop. He had undergone radiofrequency ablation about 3 weeks prior. Initial evaluation for stroke with computed tomography (CT) of head and CT angiography (CTA) of head/neck was negative. He was intubated for airway protection. Upon insertion of the nasogastric tube, it had dark blood concerning for an upper gastrointestinal bleed. The hospital course was complicated by sinus bradycardia and severe hypotension requiring dopamine and norepinephrine infusions. Repeat CTA head/neck demonstrated new evolving infarcts in the left middle cerebral artery (MCA), left posterior cerebral artery and right MCA territories. During an esophagogastroduodenoscopy to rule out atrioesophageal fistula, patient had a vasovagal episode which resolved with epinephrine. Subsequent transesophageal echocardiogram (TEE) demonstrated an echogenic long protruding thrombus extending across the iatrogenic atrial septal defect from the right atrium to the posterior wall of the left atrium, attached near the ostium of the right lower pulmonary vein. Repeat CT head multiple new areas concerning for developing infarctions and pneumocephalus. Given his overall grim prognosis, the patient was transitioned to comfort care. Conclusions: As ablative procedures for management of AF become more prevalent, it is imperative to maintain a high clinical suspicion for rare but fatal complications which require prompt diagnosis and early aggressive management.
Abstract 15210: Qualitative Stress Perfusion American Heart Association Plot and Outcome Prediction Using Artificial Intelligence
Authors: Ebraham Alskaf, Cian Scannell, Avan Suinesiaputra, Richard Crawley, Alistair Young, Divaka Perera, Amedeo Chiribiri
Journal: Circulation (2023)

Introduction: Stress perfusion cardiac magnetic resonance (CMR) is a guidelines-backed non-invasive test for the assessment of coronary artery disease (CAD), and its prognostic value is well validated. However, image interpretation requires a high level of expertise. Furthermore, the direct relationship between image pixels and outcome is not well understood. Hypothesis: Qualitative stress perfusion map based on American Heart Association (AHA) segmentation and direct linkage with outcome can be achieved using artificial intelligence. Methods: Retrospective CMR data collection was performed in one center between 2011 and 2021. Cases with death events were identified. Mean time to event was considered as a follow-up period, and cases without events and with shorter duration from CMR to collection date were excluded. Stress perfusion images were selected from 3 left ventricular (LV) levels: basal, mid and apical. Clinical CMR reports with binary AHA perfusion values were available. Six convolutional neural networks (CNNs) were trained to predict AHA segments values for each level and merged into four CNNs for the apical level. Perfusion, scar image pixels and clinical data were transformed into features, and a hybrid CNN (HNN) was trained to predict mortality. Training, validation, and test split was 70%, 15%, and 15%, respectively. Evaluation metrics included area under curve (AUC). Results: Total number of cases included for AHA plot classification were 2139 (6417 perfusion images). The average AUC for AHA perfusion classifiers was 61%, an example with correct predictions is presented. Follow-up period was calculated at 999 days. Total number of cases included for HNN development was 1294. HNN achieved high prediction value with AUC of 81%. Conclusions: Qualitative AHA stress perfusion map was feasible using artificial intelligence. Outcome prediction with HNN was a powerful new approach for risk stratifying patients with known or suspected CAD.
Abstract 12857: Electrocardiographic Findings in Women With Ischemic Sudden Cardiac Death and Anatomic Left Ventricular Hypertrophy
Authors: Ida Hookana, Anette Eskuri, Lauri Holmstrom, Juha Vahatalo, Tuomas Kentta, Jani Tikkanen, Lasse Pakanen, Juha Perkiomaki, Heikki Huikuri, Juhani Junttila
Journal: Circulation (2023)

Background: Sudden cardiac death (SCD) is a major mode of death worldwide. Previous SCD studies have shown that left ventricular hypertrophy (LVH) is a risk factor for SCD, especially in the presence of myocardial scarring or ischemia. Due to the lower incidence, women are often underrepresented in SCD studies and therefore, most recognized SCD risk factors are biased towards men. Aim: The aim of this study was to investigate sex-specific ECG findings in subjects with ischemic SCD and LVH. Methods: The study population was derived from the FinGesture study, which has collected all SCD cases from Northern Finland 1998-2017. All SCD cases underwent medicolegal autopsy to determine the cause of death. In the present study, we selected SCD cases with coronary artery disease (CAD) and anatomic LVH at autopsy, of whom antemortem electrocardiogram (ECG) was available for 483 subjects (24.4 % women; 75.6 % men). Antemortem recorded ECGs were obtained from medical records and independently analyzed by two investigators. Results: The prevalence of pathological Q-waves (11.9 % vs. 22.1 %, p = 0.016) and fragmented QRS (fQRS) (43.9 % vs. 56.4 %, p = 0.033) was lower in women compared to men. In addition, women were less likely to have prolonged QTc duration (17.8 % in women vs. 32.3 % in men, p = 0.003). The only ECG finding that appeared as more prevalent in women with anatomic LVH was ECG-LVH by Cornell’s criteria (26.4 % vs. 12.4 %, p = 0.002). The prevalence of having abnormal ECG was slightly lower in women (82.2 %) compared to men (89.2 %), p = 0.054. There were no significant differences between sexes when comparing the prevalence of anatomic LVH in subjects with ECG-LVH and ischemic SCD (90.6 % in women vs. 84.9 % in men, p = 0.524). Conclusions: Except for ECG-LVH by Cornell’s criteria, women with ischemic SCD and anatomic LVH were less likely than men to have ECG findings that are often associated with an increased risk of SCD.