tbuckley/cabot-search huggingface dataset:
Abstract 15206: Prevalence of Myocardial Adipose Tissue in Non-Ischemic and Ischemic Victims of Sudden Cardiac Death
Authors: Henrik Appel, Lasse Pakanen, Anne Ahtikoski, Lauri Holmstrom, Kerkelä Risto, Heikki Huikuri, Riitta Kaarteenaho, Juhani Junttila
Journal: Circulation (2023)

Background: Recent imaging studies have shown that patients with myocardial infarction scar who have ventricular arrhythmias show more adipose tissue around the scar. Similar changes are seen in ARVC. Purpose: The aim of this study was to determine the prevalence of myocardial adipose tissue that co-localize with fibrosis in non-ischemic and ischemic sudden cardiac death (SCD) victims. Methods: The ischemic and non-ischemic subjects were derived from the FinGesture cohort, consisting of autopsy verified consecutive victims of SCD in Northern Finland between years 1998-2017 (n=5,869). Total of 48 non-ischemic, 47 ischemic and 37 accidental/intoxication related death subjects were included in the study. Hematoxylin-eosin-stained slides were digitized and fibrofatty deposits was determined using virtual microscopy software. Results: Myocardial adipose tissue was present in 51% of ischemic cases, 29% of non-ischemic cases and 14% of controls (p&lt; 0.001). In ischemic cases, BMI seems to be associated with the presence of myocardial adipose tissue. Mean BMI was higher in subjects with myocardial adipose tissue versus subjects without (29.2 vs 24.9. p=0.022). Conclusions: The findings suggest that adipose tissue might have an influence in creation of fatal arrhythmias in SCD as it does in scar related ventricular arrhythmias. In addition, it seems that obesity is associated with ischemic scar related adipose tissue metaplasia.
Abstract 18382: Clinical and Genetic Associations of Deep-Learning Estimated Peak Oxygen Consumption From the Resting 12-Lead Electrocardiogram
Authors: Shaan Khurshid, Timothy Churchill, Lu-Chen C Weng, James Pirruccello, Samuel Friedman, Nathaniel Diamant, Christopher Reeder, Pulkit Singh, Mahnaz Maddah, Anthony A Philippakis, Aaron Baggish, Jennifer E Ho, James S Guseh, Patrick T Ellinor
Journal: Circulation (2023)

Introduction: Oxygen consumption at peak exercise (VO2 peak ) is the gold standard for cardiorespiratory fitness, but prior genome-wide association studies (GWAS) have been limited by the availability of cardiopulmonary exercise testing (CPET). Recent deep learning methods to estimate VO2 peak from the resting 12-lead electrocardiogram (ECG) may enhance genetic studies of cardiorespiratory fitness. Methods: We applied a validated deep learning model (Deep ECG-VO2) to estimate VO2 peak among UK Biobank participants with a 12-lead ECG. We assessed for associations between estimated VO2 peak and incident hypertension, diabetes, and atrial fibrillation (AF) using Cox proportional hazards models adjusted for age and sex, and plotted cumulative risk of each outcome stratified by tertile of estimated VO2 peak . We then performed a multi-ancestry GWAS of estimated VO2 peak using BOLT-LMM, adjusted for age, sex, array, and the first five principal components of ancestry. Candidate genes were prioritized based on proximity to the lead variant. Results: We applied Deep ECG-VO2 to estimate VO2 peak using the resting 12-lead ECG of 40,801 UK Biobank participants (age 65±8, 52% women). Greater estimated VO2 peak was associated with lower risks of hypertension (hazard ratio per 1-standard deviation 0.76, 95% CI 0.70-0.83), diabetes (0.60, 95% CI 0.53-0.67) and AF (0.82, 95% CI 0.74-0.90). Cumulative risk of each outcome was higher with decreasing estimated VO2 peak ( Figure ). In a GWAS of estimated VO2 peak within 39,716 participants with genetic data (age 65±8, 52% women, 90% European), we identified 10 novel genome-wide significant loci, including variants near genes involved in cardiac structure ( CCDC141/TTN, BAG3) , cardiac conduction ( SCN5A ), and adiposity ( FTO ). Conclusions: Leveraging artificial intelligence-enabled estimation of VO2 peak from the resting 12-lead ECG, we identify 10 novel common genetic variants associated with cardiorespiratory fitness.
Abstract 16270: Pulse Pressure Amplification Contributes to the Exaggerated Peripheral Blood Pressure Response to Exercise in Patients With HFpEF
Authors: Denis J Wakeham, Matthew M Howrey, Joetsaroop Bagga, Tiffany M Brazile, Bryce Balmain, Andrew R Tomlinson, James P Macnamara, Tony Babb, Benjamin D Levine, Christopher Hearon, Satyam Sarma
Journal: Circulation (2023)

Background: Patients with suspected heart failure and preserved ejection fraction (HFpEF) undergo invasive (right heart catheterization) cardiopulmonary exercise testing (iCPET) to confirm diagnosis. During iCPET peripheral arterial blood pressure (BP) is measured using a brachial cuff or radial arterial catheter. Notably, peripheral BP is typically higher than central BP and this difference is assessed by measuring pulse pressure amplification (PPA; peripheral - central PP; PP = systolic BP [SBP] - diastolic BP). The effect of PPA on the assessment of (exaggerated) exercise BP in HFpEF is unknown. Methods: 20 patients with HFpEF (75% Female; age: 69±7 years, BMI: 38±7 kg/m 2 ) were studied at rest and during submaximal and maximal cycling exercise. We measured radial BP (arterial catheterization) and derived ascending aortic BP using a transfer function applied to radial arterial waveforms (SphygmoCor). Pulse pressure amplification was assessed as radial-aortic pulse pressure. Data were compared with one-way and two-way (Site*Exercise Stage) ANOVA. Results: The increase in radial PP with exercise was greater than aortic PP (Site*Stage P&lt;0.001; Figure A); thus, PPA increased with exercise (ANOVA, P =0.001; Figure B). The increase in PPA was due to a greater increase in radial compared to aortic SBP (Site*Stage P=0.002; Figure C). The change in diastolic pressure was not different between sites (Figure D). Increases in PPA accounted for ~30% of the increase in radial SBP. The incidence of exaggerated exercise SBP (Male: &gt;210 mmHg; Female: &gt;190 mmHg) was higher in the radial artery compared to aorta (95 vs 40 %, χ2&lt;0.001). Conclusion: Peak exercise SBP was ~50 mmHg greater in the radial artery compared to aorta. The marked overestimation of central BP during exercise when measuring peripheral BP leads to misguided interpretation of BP responses to exercise, the magnitude of afterload and has implications for the assessment of ventricular-arterial coupling.
Abstract 15106: Echocardiography versus Cardiac Magnetic Resonance-Quantification of Right Ventricular Function to Stratify the Risk of Appropriate Defibrillator Therapy
Authors: Toshinori Chiba, Takatsugu Kajiyama, Yusuke Kondo, Masahiro Nakano, Ryo Ito, SATOKO RYUZAKI, Yutaka Yoshino, Yuya Komai, Yukiko Takanashi, Yoshio Kobayashi
Journal: Circulation (2023)

Background: Right ventricular dysfunction is recently referred as an independent predictor of sudden cardiac death. The purpose of this study was to evaluate the efficiency of risk stratification methods for appropriate implantable cardiac defibrillator (ICD) therapy using two different modalities to quantify the right ventricular function. Methods: Consecutive patients undergoing ICD implantations who completed both preprocedural echocardiography and cardiac magnetic resonance (CMR) were retrospectively enrolled. Any channelopathy or arrhythmogenic right ventricular disease were excluded. The right ventricular fractional area change (RVFAC) and estimated pulmonary artery pressure (EPAP) were calculated from echocardiography. The contraction-pressure index (CPI) was defined as the quotient of the RVFAC divided by EPAP. The right ventricular ejection fraction (RVEF) was automatically provided by CMR. Both were evaluated to predict the initial appropriate ICD therapy. Results: In total, 111 patients (59.5±14.9 years, 79 males) including 20 with ischemic cardiomyopathy were retrospectively enrolled. Fifty-six patients received an ICD as secondary prophylaxis. The mean RVFAC, CPI, and RVEF were 36.7±8.9%, 1.4±0.7%, and 39.9±13.8%, respectively. Regarding appropriate ICD therapy events, the best cut-off value of the RVFAC was 34.8 (specificity 0.63, sensitivity 0.65, ROC-AUC 0.64), CPI 1.59 (specificity 0.42, sensitivity 0.94, ROC-AUC 0.61) and RVEF 43.0 (specificity 0.48, sensitivity 0.87, ROC-AUC 0.64). The hazard ratio of a low RVFAC was 3.13 (95%CI: 1.32-7.44, P&lt;0.01, concordance=0.62), that of low CPI was 9.60 (95%CI: 1.27-72.4, P=0.03, c=0.65), and that of reduced RVEF was 5.55 (95%CI: 1.64-18.7, P&lt;0.01, c=0.67). Conclusion: CPI and RVEF were similarly associated with an increased appropriate ICD therapy. The CPI seemed to provide an equivalent stratification for the risk of appropriate ICD therapy as compared to a CMR indicator.
Abstract 13695: Finerenone Added to RAS/SGLT2 Blockade for Non-Diabetic Chronic Kidney Disease. Results of a Preclinical Double-Blinded Randomized Controlled Trial
Authors: Zhihui Zhu, Hans-Joachim Anders
Journal: Circulation (2023)

Introduction: Dual inhibition of the renin-angiotensin system (RAS) plus sodium-glucose transporter (SGLT)-2 or plus the mineralocorticoid receptor (MR) demonstrated additive renoprotective effects in large clinical trials. Hypothesis: We hypothesized that triple therapy with a combination of RAS/SGLT2/MR inhibitors would be superior to dual RAS/SGLT2 blockade in attenuating CKD progression Methods: We performed a preclinical randomized controlled trial (PCTE0000266) in Col4a3-deficient mice with established Alport nephropathy. Treatment was initiated late (6 weeks of age) in mice with elevated serum creatinine and albuminuria and in presence of glomerulosclerosis, interstitial fibrosis and tubular atrophy. We block-randomized 40 male and 40 female mice to either nil (vehicle) or late onset food admixes of ramipril monotherapy (10 mg/kg), ramipril plus empagliflozin (30 mg/kg), or ramipril plus empagliflozin plus finerenone (10 mg/kg). Primary endpoint was mean survival. Results: Mean survival was 63.7 ± 10.0 days (vehicle), 77.3 ± 5.3 days (ramipril), 80.3 ± 11.0 days (dual), and 103.1 ± 20.3 days (triple), respectively. Sex did not affect outcome. Histopathology, pathomics, and RNA sequencing revealed that finerenone mainly suppressed the residual interstitial inflammation and fibrosis despite dual RAS/SGLT2 inhibition. Conclusions: This preclinical randomized controlled trial suggests that triple RAS/SGLT2/MR blockade may substantially improve renal outcomes in Alport syndrome and possibly other progressive chronic kidney disorders for synergistic effects on the glomerular and tubulointerstitial compartment, respectively.
Abstract 16580: Cardiovascular Disease in Cushing Syndrome, Conns Syndrome and Malignant Pheochromocytoma: Which Adrenal Disorder is Associated With Thromboembolism and Cardiac Tumors?
Authors: Bilal Hussain, Ahmed M Mahmood, Luay Alalawi, christel cuevas, Sohail Khan, Fahad Waqar, Mohammad M Ansari, Thomas Alexander
Journal: Circulation (2023)

Background: Adrenal disorders result in worse cardiovascular outcomes. Literature suggests that Cushing (CUSH) and Conn’s syndrome (CONS) are associated with coronary artery disease, congestive heart failure (CHF), arrhythmia and stroke. But the date comparing the association of various adrenal disorders with cardiovascular disease (CVD) is limited. We reviewed the prevalence of CVD in CUSH, CONS, and malignant pheochromocytoma (MPH) and explored their prognosis. Methods: A retrospective cohort analysis was conducted using National Inpatient Sample 2016-2020. Cohorts of patients hospitalized for CUSH, CONS, MPH and CVD were identified using respective ICD-10 codes. Primary endpoint was outcomes of CUSH, CONS, and MPH in terms of CVD. Multivariate logistic regression model was used to assess prognostic outcomes. Results: 58060 patients were admitted with CUSH, 3420 with CONS, and 1445 with MPH. CONS has the highest odds of association with CVD (OR 4.87, CI 3.74-6.3, p&lt;0.001), followed by CUSH (OR 3.45, CI 3.3-3.6, &lt;0.001), and MPH (OR 3, CI 2.1-4.3, p&lt;0.001). Upon subgroup analysis of CVD, we observed that CUSH has strongest association with venous thromboembolism (VTE, OR 2.56, CI 2.3-2.8, p&lt;0.001), pulmonary embolism (PE 2.3, OR 2.03-2.6, p&lt;0.001), and CHF (OR 2.2, CI 2.1-2.3, p&lt;0.001). CONS has highest odds of association with primary cardiac tumors (9.2, CI 1.29-65.3, p=0.027), hypertension (HTN, OR 2.8, CI 2.34-3.3, p&lt;0.001), and atrial fibrillation (AF, OR 1.66, CI 1.32-2.06, p&lt;0.001). While MPH is strongly associated with higher odds of pulmonary edema (OR 3.89, CI 1.71-8.8, p&lt;0.01), and HTN (OR 2.8, CI 2.1-3.6, p&lt;0.001). Conclusion: Most prevalent CVD in adrenal disorders are HTN, IHD, CHF, and AF. CONS has highest prevalence and strongest association with CVD followed by CUSH and MPH. CUSH is strongly associated with thromboembolism while CONS with primary cardiac tumors, and MPH with pulmonary edema.
Abstract 18381: Long-Term Coronary Artery Disease Risk in Female Adults With <i>Surgically-Induced Menopause</i> : A Systematic Review
Authors: Natalie Kearn, Emma A Mensour, Kiera Liblik, Barkha Sirwani, Martha Gulati, Nilah Ahimsadasan, Amer Johri
Journal: Circulation (2023)

Introduction: Coronary artery disease (CAD) is a leading cause of morbidity and mortality in female adults. Prior studies have suggested an association between surgically-induced menopause (SIM) and long-term CAD risk. Yet, the pathophysiology and clinical significance of this relationship remains unclear. As SIM causes a premature cessation of potentially cardioprotective hormones, this review aimed to further investigate if SIM is a risk factor for CAD. Methods: SCOPUS, Web of Science, Cochrane Library, OVID/Embase, SciELO, and LILACS were searched from inception to April 2023 for observational studies reporting the effects of hysterectomy, oophorectomy, and/or salpingectomy prior to age fifty on long-term CAD risk. Results: Among 3056 identified records, nineteen studies were included with a combination of benign and malignant surgical indications. The studies reported on coronary heart disease (n=6), CAD (n=4), ischemic heart disease (n=3), and myocardial infarction (n=7). Sixteen articles with an average of 106,433 participants per study demonstrated a significantly increased risk of CAD following SIM (Table 1). In particular, hysterectomy with or without bilateral oophorectomy, and bilateral oophorectomy alone were found to have the most profound influence. Unilateral oophorectomy or hysterectomy with salpingo-oophorectomy did not appear to increase CAD risk. Average follow-up duration after SIM ranged from six to twenty-four years. Five studies adjusted for post-menopausal hormone replacement therapy use. Conclusions: SIM may elevate long-term CAD risk following hysterectomy and/or bilateral oophorectomy. Given that the majority of SIM are performed pre- or peri-menopausal for benign indications, understanding the associated cardiovascular risks is vital for informed decision-making, early detection, and prevention.
Abstract 13972: Metabolic Reprogramming of Diabetic Mesenchymal Stromal Cells by Inhibiting Glypican 3 Enhances Their Cardioprotective Functions via Pyruvate Kinase Activation
Authors: Darukeshwara Joladarashi, Charan T Gurrala, Ajit Magadum, Vandana Mallaredy, MAY TRUONGCAO, Andrew A Gibb, Cindy Benedict, Zhongjian Cheng, Raj Kishore
Journal: Circulation (2023)

Mesenchymal stromal cells (MSC) represent promising stem cell therapy for the treatment of cardiovascular diseases. Diabetes affects the functional capability of MSC and is an impediment to cell-based therapy. However, the impact of diabetes on MSC myocardial reparative activity, metabolic fingerprint, and the mechanism of dysfunction is still poorly understood. Therefore, our study aimed to understand the molecular basis of diabetes-induced MSC functions and their metabolic mechanism, and potential metabolic reprogramming of diabetic MSC to reverse these dysfunctions may represent a strategy to enhance cell-based therapeutics for myocardial repair in diabetic patients. The seahorse and 13 C glucose tracing studies identified defective energy metabolism in db/db-MSC. Our data also shows the diminished functional activity of db/db-MSCs to improve post-MI cardiac functions. Furthermore, we found that glypican-3 (GPC3), a heparan sulfate proteoglycan, is highly upregulated in db/db-MSC when compared to WT-MSC. GPC3 overexpression in WT-MSC showed abrogated metabolic fingerprints, lowered immunosuppression activity, and reduced angiogenic potential. Interestingly, GPC3 knockdown in WT-MSC showed an improved metabolic state, increased immunosuppression activity, and enhanced angiogenic potential. Furthermore, GPC3 knockdown in diabetic MSC restored their energy metabolism and their functions. Mechanistically, we revealed that GPC3 binds to pyruvate kinase (PK), which subsequently increases the rate of glycolysis and ATP production. In a mouse model of myocardial infarction (MI), intramyocardial transplantation of GPC3-metabolic reprogrammed db/db-MSC promoting neovascularization (at 28 days, post-MI) and lower cardiac fibrosis, leading to improved left ventricular function. These findings indicate that diabetes increased GPC3 expression and altered the metabolic rates in MSC which is detrimental to its function, and transplantation of GPC3-metabolic reprogrammed db/db-MSC into ischemic myocardium promoted their cardiac functions. Thus, inhibiting GPC3 may potentially be used to restore the metabolic state and functions of db/db-MSC for cell therapy applications.
Abstract 15290: Race Stratified Prevalence and Predictors of Major Adverse Cardiac and Cerebrovascular Events in a Nationwide Multicentric Elderly Cohort Hospitalized With Heart Failure With Preserved Ejection Fraction From 2016-2019
Authors: Avilash Mondal, Poojan Parmar, SRIHARSHA DADANA, Bhaswanth Bollu, Qiming Dong, Maneeth Mylavarapu, Nimra Shafi, Abeera Kali, Muhammad Hassan Khan, Srija Shanker, Samia butt, Rupak Desai
Journal: Circulation (2023)

Background: Race-stratified predictors of adverse cardiovascular and cerebral events in heart failure with preserved ejection fraction (HFpEF) have never been described before. Methods: Using the National Inpatient Sample (2016-2019), we identified hospitalizations among elderly (&gt;=65 years) HFpEF patients using relevant ICD-10 codes. Prevalence and trends of MACCE events were identified across sex and race from 2016 to 2019. Logistic regression analysis was used to estimate predictors of MACCE events across different racial groups. P&lt;0.05 is considered significant. Results: Of 6,134,669 total elderly HFpEF, 21% (n=780,615, males=13.5%) had MACCE events during hospitalization. MACCE events showed an uptrend from 2016-2019 across both males, females (13.5% vs.12.2%) and all racial groups with most difference seen in Native Americans (10.7 to 14.8%) and the least in Whites (12.0% to 12.9%) (Fig. 1). After stratification by race, hypertension had the highest odds of predicting a significant MACCE event in Hispanics (OR 2.06), while diabetes in whites (OR 1.05). Paradoxically, hyperlipidemia was associated with significant lower odds of MACCE in whites (OR 0.94), blacks (OR 0.94), and hispanics (OR 0.93), and smoking in whites (OR 0.78), blacks (OR 0.72), hispanics (OR 0.77), and asians (OR 0.77) (Table 1). Conclusion: Cardiovascular events in elderly HFpEF patients increased over the past four years, with Native Americans being the most affected. Hypertension was found to be the strongest predictor in hispanics, whereas in whites it was diabetes. Future studies are warranted to investigate the predictors of MACCE in specific racial groups to curtail worse outcomes.
Abstract 16424: Comparative Outcomes of Interventions for Peripheral Arterial Disease in Patients With Different Atherosclerotic Cardiovascular Disease Risk Estimates
Authors: Joshua Huttler, Yasser Jamil, Zhen Wu, Martin Slade, Cassius I Ochoa
Journal: Circulation (2023)

Introduction: The atherosclerotic cardiovascular disease (ASCVD) Risk Estimator is an effective tool for predicting cardiovascular events. While peripheral arterial disease (PAD) represents an advanced form of atherosclerosis, ASCVD scores have not been studied in this patient population. This study will evaluate ASCVD risk scores in patients undergoing lower extremity revascularization (LER) for PAD and assess their impact on outcomes. Hypothesis: Patients with high ASCVD risk have worse outcomes after LER for PAD compared to those with lower risk. Methods: Electronic medical records of patients undergoing LER for PAD in a single center from 2013-2020 were reviewed. The ACC/AHA ASCVD estimator was used to calculate risk and categorize patients into risk groups before initial LER. Patient characteristics and outcomes were compared between those with high (≥20%) and lower (&lt;20%) risk scores. The lower risk group was composed of patients with intermediate, borderline, and low ASCVD risk. Results: A total of 635 patients were included and 429 (67.6%) had high ASCVD risk scores. Most patients in the lower risk group had intermediate (78%, N=161) risk, followed by low (12%, N=28), and borderline (8%, N=17) risk scores. High risk patients were more commonly males with more severe comorbidities. ( Table) Patients with high ASCVD risk had more long-term mortality (29% vs 19%, P=0.010) and inferior amputation-free survival ( Figure ) compared to those with lower risk. Conclusions: Most patients with PAD undergoing LER have high ASCVD risk. High ASCVD risk scores correlate with outcomes and may be useful for risk stratification in PAD patient populations with advanced atherosclerosis.
Abstract 14780: Characterization of HFrEF and HFpEF According to Three Categories of Risk Factors: Modifiable, Non-Modifiable, and the Social Determinants
Authors: Angelina Dhani Mohamed, Khaled Elfert, Lynn Zaremski
Journal: Circulation (2023)

Background: The prevalence of HF is expected to rise in the next decade. In this cross-sectional study, we aim to explore HF according to three categories of risk factors involved in its development: modifiable, non-modifiable, and social determinants. Methods: We conducted a cross-sectional study using the National Inpatient Sample(NIS) Database. The variables in NIS were defined using the ICD-10-CM. The study population was from 2016 to 2020, aged 18 years and above. We included patients admitted to the hospital with a principal diagnosis of HFrEF or HFpEF. Exclusion criteria included patients with isolated right heart failure and uncategorized HF. We analyzed the hospital location and baseline patient characteristics, including, race, age, income, smoking, alcohol and drug abuse, and comorbidities. The primary outcome was inpatient mortality. The data were analyzed with STATA software. Results: A total of 951,714 patients were included; 502,490 had HFrEF and 449,225 HFpEF with a mean age of 67.4 and 74.4 respectively. The HFrEF group had more men (63%) and the HFpEF group had more women (62%) (A). Patients in the 1 st income (lowest) quartile constituted the largest proportion of HFrEF and HFpEF compared to the other quartiles (B). We noted a statistically higher proportion of patients with HFrEF compared to HFpEF in the 1st income quartile (35 vs. 29% respectively). In the 4th quartile, HFpEF was more common than HFrEF (20 vs. 17% respectively ) (B). HTN (64%), DM (41%), renal failure (39%), and COPD (41%) were the most common comorbidities in both groups. Smoking, alcohol abuse, and drug use were more frequent in patients with HFrEF than HFpEF being 20 vs. 11%, 6 vs. 3%, and 8 vs. 2% respectively. Mortality was 3% in HFrEF and 2% in HFpEF (p &lt;0.0001). Conclusion: This analysis presents data that emphasizes the importance of all three categories of risk factors, including the social determinants. It could help to develop effective interventions to reduce the future burden of HF.