tbuckley/cabot-search huggingface dataset:
Abstract 4134551: <i>Outstanding Research Award in Pediatric Cardiology:</i> Cardiomyopathy-Associated Pathogenic Variants in Pediatric Myocarditis: A Study from the Pediatric Cardiomyopathy Registry
Authors: Alicia Kamsheh, Stephanie Ware, Surbhi Bhatnagar, Lisa Martin, Teresa LEE, Jeffrey Towbin, Paul Kantor, Steven Colan, Charles Canter, Steven Lipshultz
Journal: Circulation (2024)

Background: Recent studies have demonstrated that patients with myocarditis (MC) may have a higher burden of cardiomyopathy (CM)-associated gene variants than the general population. However, data in children is limited. The Pediatric Cardiomyopathy Registry (PCMR), a large multi-center registry of children with CM, includes patients with dilated CM (DCM) secondary to myocarditis (MC). Hypothesis: We hypothesized patients with DCM secondary to MC in the PCMR have a higher burden of CM-associated gene variants than healthy controls, and clinical genetic testing in this population is rare. Aims: We aimed to: (1) calculate the prevalence of pathogenic (P) or likely pathogenic (LP) CM-associated variants in patients with DCM secondary to MC and compare to the prevalence in heart-healthy controls and (2) report the rate of clinical genetic testing in this population. Methods: The PCMR was queried to identify patients with DCM secondary to MC who underwent exome sequencing as part of a prior prospective study at 14 sites in North America. Controls from the Indiana University Biobank were matched 4:1 with cases based on genomic similarity. A curated gene list was comprised of 46 genes associated with CM. A second gene list included 102 genes associated with CM or MC in the ClinVar database. The prevalence of variants was compared using Chi-Square or Fisher’s exact tests. Results: A total of 32 patients were identified with DCM secondary to MC. Median enrollment age was 1.5 years (IQR 0.4-10.3) and 53% were female. There was no family history in 88%. The prevalence of P/LP variants from the curated list was 34.4% in cases compared to 4.7% in controls (p&lt;0.001). The prevalence of P/LP variants from the ClinVar list was 31.3% in cases compared to 6.3% in controls (p&lt;0.001). Variants were identified in 8 genes: ABCC9, ANKRD1, MYH6, MYH7, MYPN, PLN, TPM1 and TTN. No P/LP variants were found in desmosomal genes. The prevalence of variants was higher but not significantly different in older children compared to infants (45.0% vs 16.6%, p=0.1). The prevalence of variants in MC was similar to previously reported rates in all causes of DCM (34.4% vs 28.8%, p=0.5). Only 22% of cases received clinical genetic testing. Conclusion: Approximately 1 in 3 children with DCM secondary to MC carry a CM-associated P/LP variant, which is significantly higher than the prevalence in healthy controls. Given the high prevalence, routine genetic testing should be considered in this population.
Abstract 4134768: Geographic, Gender,&amp;Racial Trends in Mortality Due to Heart Failure in Coronary Artery Disease Among Adults Aged 65 and Older in the United States, 1999-2020: A CDC WONDER Database Analysis
Authors: Muhammad Abdullah Naveed, Omer Rehan Muhammad, Bazil Azeem, Sivaram Neppala, Rabia Iqbal, Ahilla Ali, Himaja Dutt Chigurupati, Talal Almas, Yasar Sattar
Journal: Circulation (2024)

Backgrounds: Heart failure (HF) associated with coronary artery disease (CAD) is a significant contributor to mortality in the elderly population of the United States. This study examines trends in HF in CAD-related mortality among adults aged 65 and older, focusing on geographic, gender, and racial/ethnic disparities from 1999 to 2020. Methods: A retrospective analysis was performed using the CDC WONDER database death certificates from 1999 to 2020. Age-adjusted mortality rates (AAMRs), annual percent change (APC), and average annual percentage change (AAPC) were calculated per 100,000 persons, stratified by year, sex, race/ethnicity, and geographical region. Results: Between 1999 and 2020, there were 6,571,263 deaths attributed to coronary artery disease (CAD) and 6,135,540 deaths related to Heart Failure (HF) in the US. Among adults aged 65 and older, HF in CAD caused 1,597,451 deaths, with 37.1% occurring in medical facilities and 30.3% in nursing homes. The AAMRs for HF in CAD decreased from 241.7 in 1999 to 156.2 in 2020 (AAPC: -2.23, p &lt; 0.000001). This reduction was significant from 1999 to 2014, followed by a slight increase from 2014 to 2020. Men consistently had higher AAMRs than women (227.4 vs. 137.1), with women experiencing a more significant decline in rates (AAPC: -3.23, p &lt; 0.000001). Racial disparities revealed the highest AAMRs among Whites (183.0), followed by American Indians/Alaska Natives (153.7), Blacks (134.6), Hispanics (123.7), and Asians/Pacific Islanders (81.6). The most significant reductions were observed in Hispanics (AAPC: -2.68, p &lt; 0.000001). Geographically, AAMRs varied, ranging from 92.1 in Hawaii to 257.3 in West Virginia, with the Midwest showing the highest mortality (191.0). Nonmetropolitan areas exhibited higher AAMRs than metropolitan areas (202.6 vs. 166.1), although both showed moderate declines over time, more pronounced in urban areas (AAPC: -2.41, p &lt; 0.000001). Conclusion: The study uncovers notable variances in HF in CAD-related mortality among elderly individuals in the United States based on race, gender, and geographic location. While the decrease in AAMRs from 1999 to 2014 indicates progress in cardiovascular care, the subsequent rise from 2014 to 2020 and enduring disparities call for specific public health measures to tackle these inequalities.
Abstract 4137902: Layer-specific Gene Expression Associated with Intima Hyperplasia in Arterio-venous Fistula
Authors: Yong He, Qiongyao Hu, Guoshuai Cai, Scott Berceli
Journal: Circulation (2024)

Background: The mechanism of hemodialysis arteriovenous fistula (AVF) vein intima hyperplasia (IH) may be specific to its layers (intima, media, and adventitia) but is poorly understood. To address this gap, we studied layer-specific transcriptomics related to IH in veins of two-stage AVF creation. Methods: Vein samples were collected during the initial creation of brachial artery-basilic vein AVF (1st stage) and vein transposition surgery 6 weeks later (2nd stage) and were sectioned in OCT. Tissues from each layer were separately collected by laser microdissection. Following Takara’s SMARTer Stranded Total RNA-Seq Pico Input protocol, libraries were constructed and sequenced in NovaSeq. The sequencing reads were processed by fastp, aligned to genome GENCODE 45 by STAR and gene-level counts were estimated by RSEM. Intima was assessed by histology. Layer-specific differentially expressed genes in pre-access or AVF veins associated with IH in AVF veins were detected by edgeR and further identified the enriched pathways and predicted functions using Qiagen IPA. Results: 44 veins were collected from 22 patients. 13,522 protein-coding genes that had a raw count of at least 10 in more than 70% of samples were included in analysis. 10 AVF veins had severe IH. Among the layers of pre-access vein, intima had the largest number of genes significantly associated with severe AVF IH and most or all these genes were upregulated (35/4, 26/2, 5/0 for the number of up/downregulated genes in intima, media, and adventitia of pre-access vein, respectively); cellular movement and immune cell trafficking were more strongly activated in intima of pre-access vein with severe AVF IH. No genes in any layer of AVF vein were significantly associated with severe AVF IH. From 1 st to 2 nd stage, more genes significantly changed expression in intima with severe AVF IH than intima without severe AVF IH (197/150 vs 144/93 for up/downregulated genes), while media (20/4 vs 149/31) and adventitia (99/27 vs 196/70) were the opposite; TGFB1, angiotensinogen, and TNF were more strongly activated in intima, while cell survival and migration were diminished in media and adventitia with severe AVF IH, respectively. Conclusion: Intima of pre-access vein has more genes associated with severe AVF IH. The layer-specific gene expression changes during AVF development and predicted functions are associated with AVF IH. These data can be used to develop layer-specific therapies to reduce AVF IH.
Abstract 4134560: Sex Differences in Repolarization Abnormalities Associated with Ventricular Arrhythmia in Mitral Valve Prolapse
Authors: Nathan Shaul, Andrew Cesmat, Abdul Chaudry, Suhani Gupta, Thelsa Weickert, Ross Simpson, Faisal Syed
Journal: Circulation (2024)

Background: Compared to men, women with mitral valve prolapse (MVP) are more likely to present with sudden death, and most women who die suddenly are premenopausal. Repolarization abnormalities are common in patients with MVP-attributed sudden death. However, differences in repolarization between men and women with MVP are not known. Hypothesis: Repolarization abnormalities are associated with ventricular arrhythmia and are more common in women than men with MVP. Aims: To investigate associations of ECG repolarization abnormalities with sex and ventricular arrhythmia in MVP. Methods: We reviewed 12-lead ECGs from 272 adults with MVP for T-wave inversion, ST segment elevation, ST depression, QTc and QT dispersion. Patients were excluded if they had prior MI, coronary artery disease, mitral valve surgery, moderate or severe LVH, heart failure, reduced left ventricular ejection fraction, atrial fibrillation or QRS duration &gt;120ms. Transthoracic echocardiograms were reviewed for mitral regurgitation, mitral annular disjunction, bi-leaflet or myxomatous MVP. Ambulatory ECGs (n=94) were assessed for NSVT or PVCs (&gt; 1% burden) and ECGs for &gt;1 PVC on any 10 second tracing. Associations were evaluated using Fisher’s exact test, Wilcoxon rank-sum test or multiple linear regression. Results: Among 272 patients, median (IQR) age was 58 (47-67) years, 162 (59.6%) were women, 46 (16.9%) were African American, and 34 (12.5%) had frequent ventricular ectopy. Women and men had similar rates of NSVT (15/66 [22.7%] vs 4/28 [14.3%], p=0.41) and frequent ventricular ectopy (25/162 [15.4%] vs 9/110 [8.1%], p=0.093). The QTc was longer in women (433 [417, 446] vs 423 [406, 442] ms, p=0.023) and in those with NSVT (437 [421, 444] vs 421 [405, 436] ms, p=0.028), but not in those with ventricular ectopy (437 [420, 445] vs 428 [410, 444] ms, p=0.15). There was a trend towards increased QTc in patients with mitral annular disjunction (433 [418, 454] vs 429 [408, 444] ms, p=0.054) and myxomatous MVP (434 [414, 450] vs 427 [408, 444] ms, p=0.076). Female sex was the only independent predictor of QTc (R 2 =0.14, p=0.0032). Conclusion: Among patients with mitral valve prolapse, women have longer QT interval than men, and longer QT interval is associated with nonsustained ventricular tachycardia. Subtle or dynamic delay in repolarization may promote malignant ventricular arrhythmias in women. Understanding these relationships may help identify patients at risk for sudden death.
Abstract 4134712: Pheochromocytoma-Induced Cardiomyopathy Requiring Mechanical Support with Ejection Fracture Recovery Following Surgical Resection
Authors: Grant Garrison, Lauren East, Charles Wanna, Jose Tallaj, Stephen Clarkson
Journal: Circulation (2024)

Introduction: Pheochromocytomas are catecholamine-secreting tumors that arise from chromaffin cells of the adrenal medulla. The annual incidence is approximately 0.8 per 100,000 persons, though this is an underestimate given a high percentage diagnosed at autopsy. Classically, patients present with episodic headache, sweating, and tachycardia, however, pheochromocytomas can be associated with cardiomyopathy secondary to the catecholamine excess. We present an unusual case of pheochromocytoma-induced cardiogenic shock highlighting an excellent use of mechanical circulatory support with Impella and Extracorporeal Membrane Oxygenation (ECMO) bridging to surgical intervention resulting in left ventricular ejection fraction (LVEF) recovery. Case Description: A 49-year-old female with past medical history of asthma initially presented to an outside hospital for palpitations, chest pain, and hypertension. Transthoracic echo (TTE) showed preserved left ventricle ejection fraction (LVEF) while cardiac MRI showed a LVEF of 43% with dilated left ventricle and diffuse global hypokinesis consistent with a dilated cardiomyopathy. She underwent a coronary angiogram demonstrating nonobstructive CAD. She was then discharged with readmission a month later at our hospital for chest tightness, palpitations, vomiting, weakness, and dizziness. Repeat TTE showed a drop in LVEF to 10-15%. She progressed to cardiogenic shock requiring BiPAP and inotrope initiation, with progressive shock and hypotension ultimately requiring Impella 5.5 and venoartrial ECMO. Abdominal imaging was notable for 4.7 x 4.2 cm right adrenal nodule and further workup with serum and urine metanephrines confirmed pheochromocytoma. While supported, the patient underwent right adrenalectomy with subsequent wean of mechanical circulatory support and biventricular recovery on TTE. Discussion: Pheochromocytoma-induced heart failure is a rare but potentially life-threatening complication from excess catecholamine effects on the myocardium. Pheochromocytomas should be considered in the evaluation of idiopathic heart failure even in the absence of symptoms related to catecholamine excess. Early detection, pharmacological management, and surgical resection may prevent progression of myocardial remodeling. Mechanical circulatory support can be a valuable adjunct in managing refractory heart failure in these patients by providing temporary hemodynamic stabilization while awaiting definitive tumor resection.
Abstract 4132742: Fractional flow reserve guided complete revascularization versus Culprit-only percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease. A meta-analysis of randomized controlled trials
Authors: OGECHUKWU OBI
Journal: Circulation (2024)

Background: Data comparing the efficacy and safety of fractional flow reserve (FFR)-guided complete revascularization (CR) to culprit-only percutaneous coronary artery intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease are limited. Method: Pubmed, Embase and Cochrane were searched for randomized controlled trails (RCTs) comparing FFR-guided CR to Culprit-only PCI in patients with STEMI and multivessel CAD. A meta-analysis was performed on primary outcomes of major adverse cardiac events (MACE) and all-cause mortality. Heterogeneity was examined with I 2 statistics. A random-effects model was used for outcomes with high heterogeneity. Results: We included 4 RCTs with 3173 patients comparing FFR-guided CR with culprit-only PCI in patients with STEMI and multivessel coronary artery diseases. The pooled results of the 4 RCTs showed that MACE (RR=0.66; 95% CI [0.45, 0.99]; p=0.01; 16.8% vs 24.1%), PCI revascularization (RR=0.50; 95% CI [0.37, 0.67]; p&lt;0.00001; 13.1% vs 24.9%) and unplanned revascularization (RR=0.66; 95% CI [0.44, 0.99]; p=0.04; 8.7% vs 12.9%) were significantly reduced in the FFR-guided complete revascularization group compared to culprit-only PCI group. However, all-cause mortality (RR=1.09; 95% CI [0.84, 1.42]; p=0.53; 7.2% vs 6.0%), stroke (RR=1.02; 95% CI [0.38, 2.75]; p =0.97; 2.0% vs 1.8%), major bleeding (RR=0.95; 95% CI [0.54, 1.67]; p=0.87; 1.7% vs 1.7%), death from cardiovascular causes (RR=0.82; 95% CI [0.55, 1.21]; p=0.31; 3.1% vs 3.4%), MI (RR=1.09; 95% CI [0.60, 1.95]; p=0.78; 6.7% vs 6.4%), rehospitalization for HF (RR=0.72; 95% CI [0.44, 1.15]; p=0.17; 3.4% vs 5.3%), death from any cause or MI (RR=1.02; 95% CI [0.61, 1.71]; p=0.95; 14.9% vs 13.6%), any stent thrombosis (RR=1.42; 95% CI [0.35, 5.72]; p=0.62; 2.2% vs 1.4%), contrast induced nephropathy (RR=0.25; 95% CI [0.02, 2.79]; p=0.26), and CABG revascularization (RR=1.25; 95% CI [0.30, 5.15]; p=0.76) were not statistically different between groups. Conclusion: Our meta-analysis suggests that FFR-guided CR is safe and has superior efficacy to Culprit-only PCI in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease with significantly lowered incidence of MACE, PCI revascularization as well as unplanned or urgent revascularization. However, FFR-guided CR showed no beneficial effect on all-cause mortality, stroke, major bleeding and myocardial infarction.
Abstract 4134589: Evaluating risk factors of embolism in patients with cardiac myxoma: A systematic review and meta-analysis
Authors: Muhammad Ahmad Qureshi, Danyal Bakht, Omair Ahmed, Shahan Haseeb, Kartik Gupta, Omar Baqal, Mirza Muhammad Hadeed khawar, Maaz Amir, Khawar Ali, Muqaddas Hussain, Ali Akram Qureshi
Journal: Circulation (2024)

Background: Risk stratification for embolism in cardiac myxomas remains poorly explored. Goals: By this meta-analysis we studied the risk factors assicated with embolism among patients with cardiac myxoma. Methods: A comprehensive search was conducted across PubMed, Embase, Cochrane Library, and Google Scholar from their inception until January 2024. Statistical analyses were performed using Cochrane's RevMan 5.4 software. For each risk factor, the pooled odds ratio or mean difference was calculated along with the corresponding 95% confidence interval. Results: We included 18 studies in our analysis with a total population of 2601 out of which 525 patients (20.1%) had at least one episode of embolism. The pooled analyses showed that hypertension (p = 0.001), New York Heart Association I/II (p = 0.03), irregular tumor surface (p &lt;0.00001), hyperlipidemia (p &lt; 0.0001), coronary artery disease (p=0.01), high mean platelet volume (p=0.02), high tumor mobility (p&lt;0.00001), were significantly associated with increased incidence of embolism. Female gender (p = 0.03) was the only risk factor associated with reduced risk. Other factors like smoking, atrial fibrillation, tumor size, age, body mass index (BMI), diabetes, left ventricular ejection fraction (LVEF), left atrial diameter (LAD) were not significantly associated with embolism (p &gt; 0.05). Conclusion: Our study is the first to report significant pooled outcomes for gender, hyperlipidemia, coronary artery disease, mean platelet volume, and tumor mobility in the population discussed. Hypertension, New York Heart Association I/II, irregular tumor surface, hyperlipidemia, coronary artery disease, mean platelet volume and tumor mobility were significantly associated with high risk while female gender was associated with low risk of embolism. Patients with high-risk factors might benefit from early evaluation and definitive treatment (surgery).
Abstract 4134877: Sexual Minorities Cardiovascular Health Disparities Compared to Heterosexual Adults in the US: A Systematic Review and Meta-Analysis of Nearly 2 Million Cohort Patients
Authors: Ivo Queiroz, Lucas Barbosa, Maria Luiza Rodrigues Defante, Beatriz X. Mendes, Arthur Tavares, Cynthia Mesquita, Roberto Mazetto, Vanio do Livramento Junior Antunes, Camila Guida, Billy Caceres
Journal: Circulation (2024)

Background: Cardiovascular disease (CVD) remains a leading cause of death globally, yet disparities in CVD outcomes among sexual minorities compared to heterosexual adults are under-researched. Sexual minorities face unique stressors, discrimination, and barriers to healthcare, which may contribute to higher CVD risk. This meta-analysis synthesizes evidence on health disparities between sexual minorities and heterosexual adults. Methods: We searched MEDLINE, Cochrane, and Embase databases for studies published between 2002 to 2024 that compared cardiovascular health disparities between sexual minorities and their heterosexual counterparts. Outcomes were CVD, Diabetes, Hypertension, and Obesity. We pooled odds ratios (OR) for binary endpoints with 95% confidence intervals (CI) using a random-effects model. Statistical analyses were performed using R software version 4.3.2. Results: We included 9 Cross-sectional studies after minimizing population overlap, comprising 1,938,814 patients with a mean age of 47 years. There were no significant differences in the odds of CVD (OR 1.10; 95% CI 0.87 to 1.39; Figure 1 A), Diabetes (OR 0.88; 95% CI 0.74 to 1.04; Figure 1 B), hypertension (OR 1.07; 95% CI 0.97 to 1.19; Figure 2 A) and Obesity (OR 1.01; 95% CI 0.76 to 1.35; Figure 2 B) between groups. In subgroup analysis, there were higher odds of obesity in the sexual minority population when compared to their heterosexual counterparts (OR 1.29; 95 % CI 1.15 to 1.45) and higher hypertension odds in sexual minority men (OR 1.35; 95% CI 1.12 to 1.63). Conclusion: In this meta-analysis, we found no statistically significant difference in the prevalence of CVD, diabetes, and obesity between sexual minorities and heterosexuals, meaning that more studies are necessary to assess this difference. Subgroup analyses revealed sexual minority men had higher odds of hypertension and sexual minority women for obesity.
Abstract 4133122: Integrative Metabolomic Analysis of Triglyceride-Independent Lipoprotein Lipase Pathway Mechanisms for Coronary Artery Disease
Authors: Jacqueline Dron, Liying Xue, Satoshi Koyama, Art Schuermans, Jiwoo Lee, Michael Honigberg, Whitney Hornsby, Gina Peloso, Pradeep Natarajan
Journal: Circulation (2024)

Background: Strong genetic evidence supports the associations between key genes in triglyceride (TG) metabolism via the lipoprotein lipase (LPL) pathway (i.e., LPL , APOC3 , and ANGPTL3 ) and coronary artery disease (CAD). Given sparse human genetic or clinical trial evidence for other TG-modulating pathways, it is unclear if CAD risk reduction is due to reductions in TG levels alone or a secondary mechanism of action. Aim: To determine if there are TG-independent mechanisms of CAD risk reduction specific to the LPL pathway using genomics and metabolomics. Methods: We assessed the genetic effects of LPL pathway genes (67, 46, and 17 SNPs for LPL , APOC3 , and ANGPTL3 , respectively) and non-LPL pathway genes (3462 SNPs) for TG levels and 168 metabolites. We identified metabolites with associated effects that were greater than the associated effects with TG levels for LPL pathway genes and showed heterogeneity compared to the effects for non-LPL pathway genes. Cox proportional-hazards models were used to evaluate the association of candidate metabolites measured at baseline with incident CAD in participants of the UK Biobank. Models were adjusted for age, sex, TG levels, BMI, prevalent type 2 diabetes, statin, and ten PCs of genetic ancestry. Results: Among 233,719 UK Biobank participants free of prevalent CAD and with metabolite measurements, the mean (SD) age was 57.1 (8.0) years, 105,111 (45.0%) were male, and all self-reported as white. Over a median (IQR) follow-up of 11.2 (10.5-11.9) years, there were 7992 (3.4%) incident CAD cases. There were 30, 6, and 93 metabolites with significantly greater genetic effects for LPL , APOC3 , and ANGPTL3 than what was observed with TG levels, respectively. Among 20 metabolites with heterogeneity for ≥2 LPL pathway genes compared to non-LPL pathway genes, multi-variable Cox regression revealed 19 significantly associated with CAD (P&lt;3x10 -4 ). Conclusion: LPL pathway genes have convergent and distinct impacts across metabolites. While LPL and ANGPTL3 have large genetic effects on VLDL metrics, APOC3 may have genetic effects beyond lipoprotein metabolism that impact CAD risk. The extent to which these metabolites influence CAD risk beyond TG alterations requires further study.