tbuckley/cabot-search huggingface dataset:
Abstract 4144000: The association between statins and immune checkpoint inhibitor-associated cardiotoxicity
Authors: Kuan Yu Chi, Junmin Song, CHO HUNG CHIANG, Yu-Cheng Chang, HSIA yuanping, Yu Chang, Cho Han Chiang
Journal: Circulation (2024)

Background: Immune checkpoint inhibitors (ICIs) have been associated with major adverse cardiovascular events (MACE) that carry high morbidity and mortality. Statins are widely used for the primary prevention of MACE in patients with a high risk of atherosclerotic cardiovascular disease. However, the impact of statins on MACE associated with ICIs remained unclear. Research Question Is stain use associated with a reduction in MACE in patients treated with ICI? Aim To assess the effectiveness of statins on the primary prevention of MACE in patients treated with ICI. Methods: We conducted a retrospective, propensity score-matched cohort study using the TriNetX Analytics Network database. We included all adult cancer patients who were treated with an ICI between March 2011 and March 2023. We excluded patients with a history of MACE, defined as a composite of myocardial infarction, myocarditis, pericarditis, and cardiovascular death. Patients who received statins prior to ICI initiation were compared to those who did not receive statins prior to the start of ICI therapy. The primary efficacy outcome was MACE. Secondary efficacy outcomes were indivicual MACE. The safety outcomes included all-cause mortality and adverse events associated with statins. Cox proportional hazard ratios (HR) were calculated to compare study endpoints occurring within 1 year of ICI initiation between statins users and non-users. Results: Of 73,988 patients eligible for inclusion, 12,653 patients who received statins were matched to those who did not receive statins. The most common indication for an ICI was lung cancer (41%) and the most commonly administered ICI was pembrolizumab (50%). In a Cox proportional hazards analysis, patients on a statin were associated with a lower risk of MACE (HR, 0.83; 95% CI, 0.72-0.94) as compared to patients not on a statin. There was a reduction in the risk of myocardial infarction, cardiovascular death, and a lower trend of myocarditis among patients who received statins. Patients on a statin had a lower rate of all-cause mortality without an increase in adverse events. Conclusions: Statins were associated with a reduction in MACE and all-cause mortality among cancer patients receiving ICI therapy.
Abstract 4143939: A large-scale multi-view deep learning-based assessment of left ventricular ejection fraction in echocardiography
Authors: Linyuan Jing, Aaron Long, David vanMaanen, Daniel Rocha, Dustin Hartzel, Christopher Kelsey, Jeffrey Ruhl, Ashley Beecy, Youssef Elnabawi, Gil Metser, Thomas Mawson, Emily Tat, Nona Jiang, Eamon Duffy, Rebecca Hahn, Shunichi Homma, Christopher Haggerty, Timothy Poterucha, Pierre Elias
Journal: Circulation (2024)

Introduction: Recent studies using deep learning techniques have demonstrated promising left ventricular ejection fraction (LVEF) assessment from transthoracic echocardiograms (TTEs). However, most prior studies have focused on videos from a single apical view, a technique known to be subject to limitations given the regionality of LV systolic function. We hypothesized that a deep learning model trained to include echocardiographic video clips from multiple views from a large dataset will improve accuracy in LVEF assessment. Methods: We identified all adult TTEs with a clinically reported LVEF at Columbia University between 2019-2024. A view classification model was trained to identify apical 4 and 2-chamber and parasternal long and short-axis views for LVEF assessment. The internal dataset was split into train, validation and test sets to train spatiotemporal convolutional models for each of the 4 views to assess LVEF for each video clip. The median clip-level LVEF within a study was used to derive a study-level LVEF. The model was evaluated on an internal test set and a large external test set, which included all available adult TTEs from Weill Cornell Medical Center since 2011. As benchmark comparison, the previously published EchoNet-Dynamic model was also evaluated on the external test set. Results: The model was trained and validated on 97,566 internal studies, comprising 1,424,265 videos from 60,741 unique patients. The model achieved state of the art performance on the internal test set (16,396 studies), with mean absolute error (MAE) of 3.4% and root mean squared error (RMSE) of 4.6%. Multi-view results were superior to all single-view models. Model showed robust predictions on external test set (179,298 studies), with MAE of 5.6% and RMSE of 7.1% and outperformed EchoNet-Dynamic (Table). Conclusions: We developed a deep learning model trained on multiple echocardiographic views using the largest dataset to date. Our model achieved state-of-the-art accuracy in assessing LVEF with a level of agreement between the AI and cardiologist LVEF assessments comparable to cardiologist interobserver variability. Further studies are underway to study the implementation of these models within clinical systems.
Abstract 4143985: Post-acute Sequelae of COVID-19 (PASC) is Related to Endothelial Dysfunction and Elevated Asymmetric-dimethylarginine
Authors: Mohamed Ali, Shane Phillips, Brian Layden, Dawood Darbar, Abeer Mahmoud
Journal: Circulation (2024)

Introduction: Endothelial dysfunction can trigger the development and progression of cardiovascular disease. We hypothesize that cardiovascular PASC is induced by persistent endothelial dysfunction mediated via asymmetric-dimethylarginine (ADMA, the endogenous inhibitor of endothelial nitric oxide synthase). ADMA levels rise in response to viral infections, but it is usually degraded by the enzyme DDAH1, which is inhibited by chronic inflammation and oxidative stress. This study aims to determine whether cardiovascular PASC is associated with endothelial dysfunction and to clarify the role of ADMA in this relationship. Methods: We recruited subjects who had been previously infected and developed cardiovascular symptoms (PASC+), those who had been infected but did not have PASC (PASC-), and those who had never been infected (controls) (n=20 each). Groups were matched for age, sex, and BMI and underwent blood draws and fat biopsies. Vascular function was assessed in-vivo via ultrasound imaging and ex-vivo in fat-isolated arterioles. Results: Compared to PASC- and controls, PASC+ subjects exhibited 80% higher serum levels of ADMA and 40% reduced nitric oxide levels. DDAH1 activity was elevated in the PASC+, suggesting a compensatory mechanism for the elevated ADMA levels. However, PASC+ obese subjects exhibited substantially lower DDAH1 activity than non-obese subjects, which was associated with lower insulin sensitivity and higher ADMA levels. Compared to the other two groups, the PASC+ group exhibited lower brachial artery vasoreactivity, while nitroglycerin-induced dilation did not differ statistically, suggesting impaired endothelial function. In the PASC+ group, microvascular recruitment in response to reactive hyperemia was diminished, as was the ex vivo measured flow-induced arteriolar dilation and NO generation. Left ventricle (LV) dysfunction was observed in 80% of the PASC+ group, as opposed to 5% of the PASC- and controls. The LV ejection fraction and global longitudinal strain (GLS) were substantially reduced in the PASC+ group, which was correlated with higher ADMA, C-reactive protein, and troponin-1, as well as lower NO and vascular function. Obese PASC+ subjects had the highest ADMA and the lowest endothelial-dependent vasodilation and insulin sensitivity. Conclusion: Cardiovascular PASC symptoms are related to persistent endothelial dysfunction and elevated ADMA levels, which may be further exacerbated by obesity and reduced DDAH1 activity.
Abstract 4144001: Association Between Diabetes Mellitus and Angina With Nonobstructive Coronary Arteries
Authors: Nida Latif, Natasha Cigarroa, Spyridon Kostantinis, Gabriel Garcia Castro, Steffne Kunnirickal, Natalija Odanovic, Samit Shah
Journal: Circulation (2024)

Introduction: Diabetes mellitus (DM) is a risk factor for coronary microvascular dysfunction (CMD) and endothelial dysfunction. These disorders and other syndromes of angina and nonobstructive coronary arteries (ANOCA) are increasingly recognized. However, the association between DM and non-CMD ANOCA endotypes, such as vasospastic angina (VA) and symptomatic myocardial bridging (MB), is not well defined. This study aims to report the findings of coronary function testing (CFT) in patients with DM and to determine the association between DM and specific ANOCA endotypes. Methods: We conducted a retrospective study of patients who underwent clinically indicated invasive coronary angiography and CFT with intracoronary acetylcholine provocation and bolus thermodilution between January 2018 and May 2024. Data regarding patient demographics, medical history, and physiological measurements—including coronary flow reserve (CFR), index of microcirculatory resistance (IMR), fractional flow reserve (FFR), resting full-cycle ratio (RFR), and post-procedure diagnosis—were obtained. Results: 233 patients were included, 163 (70%) were female, with a mean age of 57 ± 11 years. Of the total cohort 52 patients (22.3%) had DM. Among patients with DM, 23 (44%) had CMD, 13 (25%) had VA, 6 (12%) had mixed CMD/VA, 11 (21%) had endothelial dysfunction, and 4 (7.7%) had other phenotypes such as elevated resting flow and MB. The median CFR was reduced in patients with DM compared to those without DM (2.6 vs. 3.45; p=0.001), and the median IMR was higher (28 vs. 19; p&lt;0.001). No statistically significant differences were found in the median FFR (0.89 vs. 0.9; p=0.375) or median RFR (0.91 vs. 0.93; p=0.1). The risk of having any ANOCA diagnosis was comparable between patients with DM and those without DM (risk ratio = 1.03 [0.92, 1.15]; p=0.67), but patients with DM had a significantly increased risk of CMD compared to patients without DM (risk ratio = 1.82 [1.22, 2.71]; p=0.0052). No association was observed between DM and any other ANOCA endotypes. Conclusion: Our analysis revealed that DM is associated with lower CFR, higher IMR, and an increased risk of CMD. No association was found between DM and any other ANOCA endotype. These findings align with existing data using a contemporary, reproducible CFT protocol. Future studies will explore the clinical implications of these findings and evaluate the impact of glycemic control on outcomes in this patient population.
Abstract 4143866: The Effect of S100A6 Gene Therapy on Cardiac Function in a Rat Model of Ischemic Cardiomyopathy
Authors: Leila Gholami Chookalaei, James Tsoporis, Michael Kuliszewski, Howard Leong-Poi
Journal: Circulation (2024)

Background: S100A6 is a small calcium-binding protein that is important in managing calcium storage and myocyte contractility. This protein has a low basal cardiac expression and is upregulated following Myocardial Infarction (MI). Previous experiments have demonstrated that S100A6 gene transfer improves left ventricular function after acute ischemia/reperfusion injury. Hypothesis: Delivery of S100A6 by Ultrasound-Targeted Microbubble Destruction (UTMD) after established MI model results in improved left ventricular function and prevention of adverse ventricular remodeling. Aim: Assess the impact of UTMD delivery of S100A6 on cardiac function following experimental MI. Methods: MI was induced through permanent left anterior descending (LAD) coronary artery ligation in 8-week-Spragues Dawley (SD) male rats on day 0. On day 28, by using UTMD methods, we delivered microbubbles (1×109) coupled with either 200 μg of human S100A6 mini-circle DNA or empty minicircles to the left ventricle (LV), while control animals received no therapy. The three groups were monitored weekly for four weeks post-gene delivery using serial echocardiography to follow LV function, followed by tissue collection from various regions of the myocardium. Results: At day 28 post-MI, all groups showed reduced LV ejection fraction (LVEF) and fractional shortening (FS), with LVEF and FS values of 39.47±1.49% and 19.75±2.38%, respectively. Meanwhile, healthy animals showed LVEF and FS values of (63.75±2.38% and 36.20±1.29% (p&lt;0.001). Four weeks after the UTMD delivery of the S100A6, LVEF increased to 51.14±3.7% and FS increased to 29.66±3.2% (p&lt;0.05). In contrast, the empty minicircle and control groups showed no significant improvement (38.35±2.6% and 20.66±5.2%, p&lt;0.05). The S100A6-treated group at 28 days post-treatment showed a 2.7±1.2-fold increase in the expression level of S100A6 in the border zones. Interestingly, the peri-infarct zone of S100A6-treated myocardium also had a lower expression level of the hypertrophic marker, β-MHC (0.77±0.7-fold), as compared to those of the control groups (2.48±1.63-fold). S100A6 transfection reduced infarct size (24.75±3.3%); vs control (36±4.58%), p&lt;0.05 and decreased collagen content in viable myocardium compared to the control and empty minicircle group, p&lt;0.01. Conclusion: S100A6 overexpression in the peri-infarct zone decreased both hypertrophy and fibrosis and was beneficial to the preservation of cardiac function in a model of chronic MI.
Abstract 4143918: Differences in Outcomes in Spontaneous Coronary Artery Dissection vs. Type 1 Myocardial Infarction
Authors: Mouna Kodali, Ekow Essien, Tonga Nfor, Patrycja Galazka, Matthew Klinka, Stacie Kroboth, David Boulware, Michael Peterson, Jim Kanani, Sara Walczak, Venkateswara Gogineni, Suhail Allaqaband
Journal: Circulation (2024)

Background: Spontaneous coronary artery dissection (SCAD) is a non-iatrogenic dissection in the epicardial coronary arteries, not related to trauma or atherosclerosis. In SCAD, myocardial injury occurs due to luminal obstruction following intimal disruption or intramural hematoma. We aimed to determine the differences in outcomes associated with SCAD compared to Type 1 myocardial infarction (MI) in the Aurora Health Care community. Methods: A retrospective, matched cohort, multicenter community study was carried out on adult patients aged &gt;18 years admitted to all Aurora Hospitals from January 2012 to December 2022. A total of 57 patients were diagnosed with SCAD during that period. The SCAD and Type 1 MI groups were matched by age and gender at a 1:5 ratio using a propensity score-based matching. Outcomes between the SCAD and Type 1 MI groups were compared using chi-squared tests or Fisher’s exact tests, and t-tests or nonparametric equivalents (Wilcoxon), and a time-to-event analysis. Results: SCAD patients who underwent conservative therapy were 87.7%. There were no significant differences in in-hospital outcomes between SCAD and Type 1 MI in measures such as cardiogenic shock, mortality rate, sudden cardiac death, ischemic stroke, hospital length of stay, and arrhythmias (AF, atrial flutter, supraventricular tachycardia, and ventricular fibrillation). In the long term, SCAD patients required less repeat coronary catheterization (7% vs. 24.6%, p=0.003) and PCI (1.8% vs. 11.2%, p=0.027) compared to the Type 1 MI group. Type 1 MI patients had a higher incidence of AF, atrial flutter, death, readmissions for heart failure, and diastolic and systolic function in the long term, but this was not statistically significant. Type 1 MI patients required loop diuretics in the long term (24.6% vs 10.5%, p 0.02). Conclusion: Type 1 MI patients exhibited poorer long-term prognoses characterized by a higher risk of heart failure, which likely increased the necessity for diuretics. Additionally, Type 1 MI patients showed a higher need for repeat coronary catheterization and PCI. Although SCAD and Type 1 MI present similarly as acute coronary syndrome, it is important to understand the differences in outcomes as the management of these two populations differ.
Abstract 4143986: Non-ischemic septal fibrosis on delayed enhancement CMR provides incremental prognostic value in functional tricuspid regurgitation
Authors: Pablo Villar Calle, Varun Pai, Jonathan Kochav, Caitlin Chiu, Rachel Axman, Aditya Sahai, Mahniz Reza, Letizia Ruoli, Omar Khalique, Josep Mayol, Giorgia Falco, Jonathan Weinsaft, Jiwon Kim
Journal: Circulation (2024)

Introduction: CMR enables assessment of cardiac chamber remodeling and associated alterations in myocardial tissue substrate. Primary aim of this study was to examine the relative prognostic utility of chamber remodeling and myocardial tissue alterations in patients with functional tricuspid regurgitation. Methods: The population comprised patients with advanced functional TR (≥moderate) undergoing CMR. LGE-CMR was used to identify myocardial scar/infarction inclusive of non-ischemic septal fibrosis (NIsF) which was defined as hyperenhancement in the mid-myocardial or epicardial aspect of the interventricular septum. Clinical characteristics including follow-up and all-cause mortality were obtained blinded to imaging analyses. Results: 894 pts (71±15yo; 52% male) with advanced functional TR undergoing CMR were studied; LV dysfunction was present in 44% and RV dysfunction in 57%. Paralleling ventricular dysfunction, adverse LV and RV chamber remodeling was also common, occuring in 25% and 43% of the population, respectively. Regarding tissue substrate, over half (50.4%) had LV scar/infarction (9.2±10.8 %LV), 50.8% of which represented NIsF. Prevalence of NIsF was 3-fold higher in patients with concomitant RV dysfunction versus those without (36.1% vs 11.5%, p&lt;0.001). Regarding outcomes, 215 patients died during a median follow-up of 4.6 years. As shown in Table 1 , LV and RV dysfunction, LV and RV dilation, advanced mitral regurgitation and NIsF were each linked to increased mortality risk (all p&lt;0.001). A combined model incorporating indices known to impact TR prognosis demonstrates NIsF to be independently linked to increased mortality risk even after controlling for RV dysfunction (HR 1.78 [CI 1.31-2.43]; p&lt;0.001). Kaplan-Meier analysis demonstrates significantly increased risk of death in patients with NIsF (p&lt;0.001) ( Figure 1 ). Conclusions: Among patients with advanced TR, NIsF provides incremental prognostic risk stratification beyond conventional risk markers.
Abstract 4144021: The Sodium-Potassium Pump Activations and the Sex-Specific Antiarrhythmic Action of Mirabegron
Authors: Xiao Liu, Liyang Zhang, Anxhela Kote, James Tisdale, Zhenhui Chen, Peng-Sheng Chen
Journal: Circulation (2024)

Background: β-3 adrenoceptor (AR) activation is antiarrhythmic in a canine model of ventricular arrhythmia. Na-K ATPase (NKA) expression is higher in female than male rats and is stimulated by β-3 agonist due to an inhibitory oxidative modification. Objective: To test the hypothesis that mirabegron, a β-3 agonist approved by the FDA for treating overactive bladder, has more anti-fibrillatory effects in females than in male rabbit ventricles due to NKA stimulation. Methods: We performed optical mapping studies in 6 male and 6 female Langendorff-perfused rabbit hearts at baseline, then sequentially after adding mirabegron (500 and 1000 nM), followed by ouabain (500 nM), a specific NKA blocker. All hearts underwent 10 attempts of ventricular fibrillation (VF) induction with a ventricular burst pacing (20 Hz for 10 s) at each stage of the experiment. Results: A shows phase maps during VF. Triangles indicate PSs. Mirabegron 1000 nM significantly decreased VF inducibility (number of VF induced in the 10 attempts) from 4.8±3.2 to 2.2±2.9 (p=0.034) in females but not in males (from 4.5±2.6 to 5.0±2.8, p=0.656) ( B ). Consistent with our previous reports, Mirabegron 1000 nM decreased PSs/VF (number of phase singularity per VF episode) in females (from 10.5±2.7 to 2.9±3.3, p=0.010) but not in males (from 11.3±2.3 to 9.7±2.6, p=0.167). Adding ouabain did not reverse mirabegron’s effects on PSs/VF (2.4±3.9, p=0.706) in females. However, it decreased PSs/VF significantly in males (3.4±4.0, p=0.038). Mirabegron decreased conduction velocity (CV, activation time -1 , /s) in both males (from 40.3±6.5 to 30.4±5.3, p&lt;0.001) and females (from 38.8±7.2 to 30.0±4.9, p=0.010). Adding ouabain did not further change CV in both males (31.6±8.2, p=0.434) and females (28.1± 5.3, p=0.066). Ouabain decreased APD 25 after mirabegron significantly (54.6±6.6 ms vs 68.4±3.4 ms in males, p=0.019; 51.4±6.9 ms vs 65.6±6.5 ms in females, p=0.049, 200 ms pacing cycle length), but did not change the APD 80 . Conclusion: Mirabegron reduced PSs/VF and VF inducibility more in females than males. These sex-specific antiarrhythmic effects were not affected by NKA blockade with ouabain.
Abstract 4143979: Incidence of Right Ventricular Dysfunction in an Echocardiographic Referral Cohort
Authors: Jonah Garry, Shi Huang, Jeffrey Annis, Suman Kundu, Anna Hemnes, Matthew Freiberg, Evan Brittain
Journal: Circulation (2024)

Introduction: RV dysfunction (RVD) is one of the few cardiovascular conditions with unknown incidence rate (IR). We examined the rates, risk factors, and HF hospitalization hazard associated with incident RVD in pts referred for TTE. Methods: We extracted tricuspid regurgitant velocity (TRV) and TAPSE from all TTEs at Vanderbilt between 2010-2023. We selected the first TTE with normal RV function (TAPSE =/&gt; 17mm) and a reported TRV. The primary outcome was new RVD (TAPSE &lt; 17mm) and secondary outcome was time to HF hospitalization after second TTE. We used Poisson regression and multivariable cox models to estimate IRs and hazard ratios, adjusted for demographics, comorbidities, and TTE measures. We estimated a minimum IR in all pts with a baseline echo (Full Cohort) and a maximum IR among pts with a repeat TTE (Repeat TTE Cohort). Results: We identified 45,753 pts (63 years [IQR 50-72], 45% Male, 13% Black) with normal RV function at baseline, of whom 13,735 pts (30%) underwent a repeat TTE and 4,198 pts (10%) developed RVD. The IR of RVD in the Full Cohort was 3.2/100 person-yrs (95%CI 3.1-3.3) and 8.2 (95%CI 8.0-8.5) in the Repeat TTE Cohort. IRs were higher in pts with pulmonary hypertension vs without and increased with higher RVSP ( Figure 1) . Risk factors for incident RVD included HF (HR 1.88; 95%CI 1.75–2.03), AF (HR 1.54; 95%CI 1.44–1.65), and left-sided valvular disease (HR 1.68; 95%CI 1.53–1.85). Baseline RVSP was associated with TAPSE decline beginning near 35mmg ( Figure 2A ). Incident RVD was associated with increased hazard of HF hospitalization (HR 2.02; 95% CI 1.85-2.21). Hazard of HF hospitalization increased when TAPSE declined 5mm or greater ( Figure 2B ). Conclusions: RVD incidence is substantial among patients referred for TTE and warrants close monitoring when RVSP &gt;35mmHg. Incident RVD and change in TAPSE &gt;5mm were associated with increased hazard of HF hospitalization, even after adjustment for prevalent HF.