tbuckley/cabot-search huggingface dataset:
Abstract 4143993: SEX DISPARITIES IN HUMAN CALCIFIC AORTIC VALVE STENOSIS ASSESSED BY DISEASE STAGE-SPECIFIC HISTOPATHOLOGICAL AND PROTEOMIC ANALYSES
Authors: Cassandra Clift, Mark Blaser, Florian Schlotter, Simon Robson, Simon Body, JOCHEN MUEHLSCHLEGEL, Masanori Aikawa, Sasha Singh, Elena Aikawa
Journal: Circulation (2024)

BACKGROUND: Calcific aortic valve stenosis (CAVS) is a global clinical burden, impacting around 2% of the population over 65 years of age. No pharmacotherapeutics exist, with surgical repair and transcatheter valve replacement being the only intervention. Females are underrepresented in studies of CAVS, leading to delay in timely intervention and increased mortality. Histopathology demonstrates female CAVS presents with decreased valvular calcification but increased fibrosis and severity of symptoms. We hypothesize that the underlying molecular mechanisms contributing to disease progression and fibrocalcific burden in AS differs between male and female patients. Our goal for this study is to use previously acquired proteomic datasets of a clinically-defined human AS cohort to examine sex disparities and underlying sex-specific disease signatures. METHODS and RESULTS: Age-matched human AS tissue samples (n=4 females, n=14 males) were each segmented into non-diseased, fibrotic, and calcified disease stages and analyzed using LC-MS/MS proteomics and quantitative histopathology. Unbiased principal component analysis shows sex- and stage-specific proteome clustering. AS pathogenesis drove sex-specific disparities in the valvular proteome: 338/1503 total proteins were differentially-enriched by sex across disease stages. Compared to sex-specific non-diseased controls, female fibrotic tissue resulted in 2.05-fold greater number of differentially-enriched proteins than did male fibrotic tissue (female: 113, male: 55; q&lt;0.05 threshold). In contrast, female calcific tissue identified 2.03-fold less differentially-enriched proteins than male calcific tissue (female: 255, male 519; q&lt;0.05 threshold). By Gene Ontology enrichment (odds ratio ranked, q&lt;0.05), proteins enriched in male fibrotic AS segments preferentially associate with superoxide regulation, sterol transport, and endocytosis while extracellular matrix (ECM) organization and endothelial cell migration were hallmarks of female-specific AS fibrosis. Remarkably, immune and complement response were ubiquitous drivers of calcification, female segments were uniquely enriched in ECM processes. CONCLUSIONS: We reveal a sexually-dimorphic AS proteome, including the novel overabundance of ECM remodeling pathways in female calcified aortic valve tissues. This analysis allows for identification of potential sex-specific protein drug targets implicated in AS pathobiology.
Abstract 4143857: Characterization of Arrhythmia Occurrence During Sleep and Activity in Patients Undergoing Long-Term Continuous Ambulatory ECG Monitoring
Authors: Elaine Yu, Relana Pinkerton, Ardit Kacorri, Anthony Battisti, Yuriko Tamura, Mintu Turakhia
Journal: Circulation (2024)

Background: Circadian patterns of arrhythmias based on time of occurrence have been described in small datasets, but there is little information on the relationship of arrhythmia occurrence to sleep and activity. We sought to quantify the occurrence of arrhythmias detected by long-term (≤14 days) continuous ambulatory ECG monitoring (LTCM) during sleep, wake, and activity. Methods: We performed a retrospective analysis of consecutive patients who underwent LTCM with an FDA cleared device that features an embedded accelerometer (Zio ® Monitor, iRhythm Technologies, Inc.; San Francisco CA). This feasibility analysis included nationwide patients for whom LTCM ECG data were processed on a single day (Feb 1, 2024). We applied an AI algorithm previously developed and validated as a wellness feature to classify periods of sleep, activity (≥2mph walking), and inactivity using LTCM accelerometry data. Rhythms were classified by an FDA-cleared deep learning algorithm, confirmed by a cardiographic technician and time-aligned to the algorithm-generated sleep/wake and activity/inactivity labels. Odds ratios (OR) associated with time in arrhythmia for sleep and activity periods were calculated by rhythm type. Results: Analysis included 3,840 patients (58.3% female, age 59.7±19.7 years) monitored for an average 10.5 days (Table 1); patients spent the most time in AF. Rhythms with the highest association with sleep (vs. wake) were pause (OR=2.06; 95% CI 2.00-2.12) and 3 rd degree block, (OR=1.81; 95% CI 1.79-1.83). Notably, VT was among the arrhythmias least likely to occur during sleep (OR=0.31; 95% CI 0.30-0.31). Second degree (Mobitz type 2) and third degree block had the highest OR associated with activity. Conclusion: This is the largest study characterizing sleep, wake, and activity of ambulatory arrhythmias — and obtained from only a single day of data. Results demonstrate the feasibility of integrating sleep and activity labeling with LTCM findings and the potential to give context to arrhythmias, such onset or termination during sleep, wake, or exertion.
Abstract 4143840: Transthyretin V142I Genetic Variant and Heart Failure Risk: A Multi-Institutional Analysis of US Million-Veteran Program (MVP)
Authors: Konstantinos Sideris, Lina Brinker, Tyler J. Nelson, Anthony Gao, Christos Kyriakopoulos, Kathryn Pridgen, Dan Berlowitz, Catherine Tcheandjieu, Scott Damrauer, Kyong-Mi Chang, LELAND HULL, Jacob Joseph, Jeffrey Ferraro, Fatai Y. Agiri, Steven Roblin, Craig Teerlink, Josef Stehlik, Spencer Carter, julie lynch
Journal: Circulation (2024)

Introduction: Transthyretin (TTR) dissolution into monomer form and subsequent misfolding causes amyloidosis through deposition of beta-pleated sheets in end organs. Genetic sequence variations can decrease the stability of TTR leading to earlier disease manifestation, a condition known as hereditary TTR amyloidosis (hATTR). The most common variant in the U.S. - V142I, is most prevalent in individuals of African descent. We sought to explore the relationship of V142I and cardiac manifestations of hATTR, using the Million Veteran Program (MVP) dataset. Methods: We identified all V142I carriers in the MVP dataset who had a first visit before January 2008. Carriers were matched with controls at a 1:5 ratio based on age, sex, and race. The outcome studied was development of heart failure (HF)/cardiomyopathy (CM). Cumulative incidence and multivariable Cox proportional hazards regression models were performed to compare V142I carriers with the matched control group. Results: A total of 2,658 V142I carriers (3.1% of veterans of African descent in MVP) and 13,467 matched control patients were included in our final study cohort. Carriers at baseline had a median age of 53 [46-60] years, 87.2% were male, 3.5% had HF, 34.0% had type 2 diabetes mellitus (T2DM), 8.0% had bilateral carpal tunnel syndrome (BCTS), 5.2% had spinal stenosis (SS), and 19.4% had neuropathy. Patients in the control group at baseline had a median age of 53 [46-60] years, 87.2% were male, 3.4% had HF, 33.6% had T2DM, 7.9% had BCTS, 5.0% had SS, and 19.6% had neuropathy. Cumulative incidence of HF/CM at age 70, 80 and 90 years was 23.8%, 48.0%, and 68.8% for cases, and 23.7%, 40.5%, and 56.7% for controls (p=0.006), respectively (Figure). In a multivariable Cox proportional hazards regression model, carrier status was associated with higher incidence of HF/CM - HR of 1.13 (CI: 1.03-1.23, p=0.004). T2DM, hypertension, Charleston comorbidity index and current smoking were also associated with the outcome. Conclusions: We report on higher risk of developing HF/CM in V142I variant carriers compared to controls in the MVP cohort. Further research is needed to determine the most effective diagnostic and treatment approaches in veterans who may be V142I carriers at risk of developing HF/CM.
Abstract 4143906: Prophylactic Administration Of Colchicine Mitigates Atrial Fibrillation Vulnerability Post-Catheter Ablation In Rats: Exploring Sex-Specific Variations.
Authors: Abir Attia, Ewen Le Quilliec, Charles-Alexandre LeBlanc, Feng Xiong, Patrice Naud, Jiening Xiao, Colombe Roy, Martin Sirois, Martin Aguilar, Jean-Claude Tardif, Roddy Hiram
Journal: Circulation (2024)

Background: Atrial Fibrillation (AF) is the most diagnosed cardiac arrhythmia in clinical practice. Catheter ablation (ABLA) is a method used to manage AF by cauterizing the left atrium (LA) to isolate arrhythmogenic areas. However, ABLA is paradoxically associated with atrial inflammation and AF recurrence, with 10% of patients experiencing recurrence within 30 days and over 50% after 12 months. Studies suggest that AF prevalence is generally lower in women than in men, but females with AF are more prone to severe complications. Colchicine has been proposed for its anti-inflammatory and cardioprotective effects. Hypothesis: Early colchicine treatment prevents ABLA-triggered atrial fibrosis, inflammation, and arrhythmogenic substrates. Methods: Male and female Wistar rats (225-275g) were randomly assigned to four groups: Sham or ABLA, with or without colchicine treatment (1 mg/kg/day; intraperitoneally) starting 2 hours before surgery. Sham animals underwent surgery without ABLA. In vivo electrophysiological studies and echocardiography were performed on days 1 (D1) and 3 (D3) post-ABLA. On D3, ex-vivo optical mapping was conducted on Langendorff-perfused hearts, and atrial fibrosis, gene, and protein expression were assessed using Masson's trichrome staining, qPCR, and immunoblotting, respectively. Results: ABLA animals displayed a significantly higher susceptibility to atrial arrhythmias compared to Sham animals, and among ABLA rats, females were 20% less vulnerable to AF than males at D3 post-ABLA. The LA from ABLA rats exhibited significantly slowed conduction velocity, increased fibrosis areas, and enhanced levels of inflammatory markers compared to Sham. Colchicine significantly reduced the incidence of AF post-ABLA with more efficacy in females than males. Moreover, colchicine normalized LA conduction, fibrosis, and inflammation in LA ABLA compared to Sham. Consistent with contemporary knowledge about male and female differences in AF incidence, our data suggest that endogenous female sex hormones combined with colchicine administration may contribute to significantly reducing AF incidence. Conclusion: Initiating Colchicine treatment prior to ABLA may lower post-ABLA-induced LA inflammation and AF occurrence. Delving into the variances in male and female responses to colchicine intervention could offer new insights into addressing post-ABLA AF incidence.Bas du formulaire
Abstract 4143907: Immediate versus staged percutaneous coronary intervention of non-culprit lesions in patients with st-elevation myocardial infarction and multivessel disease: a meta-analysis of 4,120 patients.
Authors: Daniel Paulino, Edwin Andrade Arbaiza, Daniel Navarro Martinez, Shirley Xiloj, Bruno Hernandez, Lissette Garcia-Mena
Journal: Circulation (2024)

Introduction: Multivessel coronary artery disease is common in patients with ST-segment elevation myocardial infarction (STEMI). Previous trials have shown that comprehensive revascularization of non-culprit arteries with significant stenosis reduces the risks of cardiovascular death, myocardial infarction, and ischemia-driven revascularization compared to culprit-only revascularization. However, the optimal timing for revascularizing non-culprit lesions—immediate versus staged percutaneous coronary intervention (PCI)—remains unclear. This meta-analysis aims to determine if staged or immediate PCI is associated with fewer major adverse cardiovascular events. Methods: A meta-analysis was conducted following PRISMA guidelines, with a protocol registered in PROSPERO (CRD42023485163). We included studies from PubMed, Embase, and Cochrane databases until October 10, 2023. Inclusion criteria were: 1) patients over 18 with STEMI and hemodynamically stable multivessel disease; 2) intervention: immediate PCI; 3) comparator: staged PCI; 4) study types: randomized clinical trials (RCTs) and cohort studies. Study quality was assessed using ROBINS-I for observational studies and ROB 2 for RCTs. Results: Nine studies met inclusion criteria: 3 RCTs and 6 cohort studies, with a total of 4,120 patients. Staged PCI was significantly associated with reduced cardiovascular death (RR = 1.77; 95% CI = 1.11-2.81; p = 0.02, I 2 = 24%) and all-cause mortality (RR = 1.83; 95% CI = 1.19-2.79; p = 0.005, I 2 = 42%). Hazard ratio analysis also favored staged PCI for cardiovascular death (HR = 4.11; 95% CI = 1.07-5.87; p = 0.04, I 2 = 12%) and all-cause mortality (HR = 8.13; 95% CI = 1.01-8.17; p = 0.05, I 2 = 37%). No significant differences were found for major adverse cardiovascular events (RR = 0.98; 95% CI = 0.74-1.28; p = 0.86, I 2 = 53%) or in major bleeding, stroke, or target vessel revascularization. Conclusion: In patients with STEMI and multivessel disease, staged coronary revascularization is associated with a lower risk of major adverse cardiovascular events, cardiovascular death, and all-cause mortality compared to immediate revascularization, without increasing adverse outcomes. Further research is needed to confirm these findings.
Abstract 4143841: Cardiomyocyte-specific PLCe1 knock-down attenuates Angiotensin II-induced cardiac hypertrophy.
Authors: Kareemah Ni, Vagner Rigaud, Patrick Vigneault, Chunyang Xiao, Carla Klattenhoff, Patrick Ellinor
Journal: Circulation (2024)

Background: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease. We have recently identified Phospholipase C epsilon 1 (PLCe1) to be upregulated in cardiomyocytes (CMs) from HCM patients. PLCe1 has been reported to play a critical role in developing cardiac hypertrophy and PLCe1 heart-specific genetic ablation in mice prevents hypertrophic growth following transaortic constriction. Aim: To further assess the therapeutic potential of PLCe1 modulation, we assessed whether PLCe1 knockdown can rescue agonist-induced cardiac hypertrophy both in vitro and in vivo. Methods: Cardiomyocyte hypertrophy was induced by endothelin 1 (ET1) stimulation in iPSC-derived CMs and primary neonatal mouse ventricular myocytes (NMVMs) followed by PLCe1 knockdown using siRNAs. For in vivo assessment, cardiac hypertrophy was induced in C57BL/6J wild type mice by implanting angiotensin II (Ang II) osmotic minipumps for 4 weeks. Adeno-associated virus serotype 9 carrying GFP-tagged shRNAs against PLCe1 (AAV9-shPLCe1) or GFP alone (AAV9-GFP; control) were delivered retro-orbitally on the day of the surgeries and 1 week after Ang II infusion. M-mode echocardiography was performed at baseline and weekly for 4 weeks. Results: PLCe1 silencing in either human iPSC-CMs or NMVMs treated with ET1 resulted in 25% reduction in cell size, 46% reduction in total protein synthesis, and 72% and 81% reduced expression of the hypertrophic markers NPPA and NPPB, respectively. To evaluate whether PLCe1 therapy can promote left ventricle hypertrophy regression, mice were infused with Ang II and subsequent delivery of AAV9-shPLCe1. Approximately 65% of the CMs were transduced within 3 days after AAV9-shPLCe1 delivery while the maximal transduction levels of 74% were observed after 1 week. We observed significant attenuation of the cardiac hypertrophic response represented by decreased wall thickness and preserved cardiac structure and function 1 week after PLCe1 modulation. Ongoing analysis of the later time points will allow us to better evaluate the salutary effects of PLCe1 therapy. Conclusion: Cardiomyocyte-specific PLCe1 knockdown attenuates Ang II-induced cardiac hypertrophy, highlighting PLCe1 as a potential target for HCM.
Abstract 4143837: Demographics and Regional Trends in Mortality associated with Atherosclerotic Cardiovascular Diseases in the Nicotine-Dependent Population: A Retrospective Study in the United States from 1999 to 2020
Authors: Ahmed Raza, Ameer Haider Cheema, Abu Huraira Bin Gulzar, Mirza Ammar Arshad, Rahman Tanveer, Haroon Sohail, Ali Hamza, Ubaid Khan
Journal: Circulation (2024)

Background: Atherosclerotic Cardiovascular Diseases (ASCVD) are a leading cause of morbidity and mortality, causing four out of every five cardiovascular (CV) deaths. Nicotine is a significant risk factor for ASCVDs. While there is comprehensive data available on mortality trends for cardiovascular diseases (CVDs) in general, the mortality data for ASCVDs in the nicotine-dependent population is still lacking. Objective: We aim to explore the mortality trends and patterns related to ASCVDs in the nicotine-dependent population of the US, stratified by different demographic and regional variables. Methods: We retrieved the data from the CDC Wonder database and determined the crude death rates (CRs) and age-adjusted mortality rates (AAMRs) per 100,000 individuals. We targeted the middle-aged and older adult nicotine-dependent population. Our study examined the changes in AAMR through annual percentage change (APC) and average annual percentage change (AAPC) using Joinpoint regression program. Results: From 1999 to 2020, a total of 912,565 deaths were reported due to ASCVDs in the nicotine-dependent population of the US, demonstrating an increasing trend (AAPC = 13.06). Males (56.63) had a higher AAMR than females (19.05). Non-Hispanic (NH) American Indians or Alaska Natives had the highest AAMR (47.16), while the NH Asians or Pacific Islanders had the lowest (7.52). The AAMRs also varied by regions, with Midwest having the highest AAMR (44.88) followed by Northeast (35.72), South (33.9), and West (25.97). The states with the highest percentage change in AAMR were New Jersey and Tennessee, while those with the lowest percentage change were California and North Dakota. Non-metropolitan areas had the highest AAMR (47.29), followed by medium/small metropolitan (39.24) and large metropolitan (28.36). Most deaths occurred at the decedent’s home (39.46%) and the medical facility (39.37%). Conclusion: We reported increasing ASCVDs-related age-adjusted mortality trends in the nicotine-dependent population of the US, with the highest AAMRs in males, NH American Indians/Alaska Natives, the midwestern region, and the non-metropolitan areas. Targeted health policy measures must be taken to address these alarming trends.
Abstract 4144202: Association of Elevated Lipoprotein(a) Levels with Adverse Outcomes in Patients with Stable Angina Undergoing Stent-less PCI with Paclitaxel-coated Balloon
Authors: Tomonori Takahashi, Tetsuzo Wakatsuki, Yoshihiro Saijo, Yutaka Kawabata, Rie Ueno, Muneyuki Kadota, Tomoya Hara, Tomomi Matsuura, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Masataka Sata
Journal: Circulation (2024)

[Background]: Evidence on the long-term prognosis of stent-less percutaneous coronary intervention (PCI) using paclitaxel-coated balloons (PBCs) is becoming established, however some prognostic indicators remain unexplored. Recently, elevated blood lipoprotein(a) levels are gaining attention as an independent risk factor for the development of atherosclerosis. We hypothesized that elevated lipoprotein(a) levels would also adversely affect the outcome of stent-less PCI. [Object]: The aim of this study is to investigate the association between lipoprotein(a) levels and outcomes after stent-less PCI. [Methods]: In this single-center retrospective study, patients with stable angina undergoing stent-less PCI with PCBs in de novo lesions at our institution were included between October 2016 and September 2022. We classified all patients into three groups according to lipoprotein(a) tertiles and performed a Cox proportional hazards analysis. The primary endpoint was a composite outcome of cardiovascular death, major bleeding, myocardial infarction, and target lesion revascularization. [Results]: A total of 207 patients were included, including a mean age of 70±11 years and 75% male. The median lipoprotein(a) level was 12.4 nmol/L (IQR 4.8-21.4 nmol/L). During a median follow-up of 18 months, the composite outcome was observed in 37 patients (17.9%). Patients with the highest lipoprotein(a) group (≧18.4 nmol/L) had a 4-fold higher risk than those with the lowest group (&lt;7.1 nmol/L) (adjusted hazard ratio: 3.98[1.46-10.83],p=0.02). [Conclusions] : Patients with high lipoprotein(a) levels may have an unfavorable outcome compared to those with low levels undergoing stent-less PCI with PCBs.
Abstract 4144037: Association Between Imaging Follow Up and 1-Year Reintervention Risk After Peripheral Vascular Intervention for Claudicatio
Authors: Gaelle Romain, Kim Smolderen, Jacob Cleman, Santiago Callegari, Mufti Rahman, Derek Knight, Carlos Mena-Hurtado
Journal: Circulation (2024)

Background: One-third of patients undergoing peripheral vascular intervention (PVI) for refractory claudication undergo a reintervention within 1 year. It is unknown whether receiving follow up imaging after PVI for claudication is associated with 1-year reintervention risk. Aim: To assess the association between receiving imaging follow-up within 3 months after PVI for claudication and 1-year reintervention risk before occurrence of major amputation. Method: We studied patients with claudication undergoing PVI who were alive and without reintervention at 3 months (2015-2018) in the Vascular Quality registry. Reintervention and imaging data were defined from Medicare data. Imaging follow-up included ankle brachial index (ABI), duplex ultrasound (DU), computed tomography angiography (CTA), and magnetic resonance angiogram (MRA) within 3 months post-PVI. We propensity-matched 1:1 for imaging follow-up status (No vs. Yes). The Aalen-Johansen method and Fine-Gray model assessed the 1-year cumulative incidence and reintervention risk (sub-hazard ratio, sHR) in patients without vs. with imaging follow-up, accounting for the competing mortality risk. Sensitivity analysis excluded ABI from imaging follow-up. Results: Each imaging follow-up status included 2,208 patients. Mean age was 71.3±8.4 years and 39.0% female. In patients with imaging, 47.1% received 1 imaging test, of which 75.1% were ABIs. Over 50% received ≥2 imaging tests within 3 months post-PVI, with 5% receiving ≥1 per month. The 1-year cumulative incidence and reintervention risk was similar in patients without vs. with imaging (17.5% 95%CI 15.9-19.2 vs. 18.8% 95%CI 17.1-19.2 and sHR 0.92 95%CI 0.80-1.06, P =0.259). When excluding ABI, the 1-year cumulative incidence and reintervention risk was lower in those without vs. with imaging (18.3% 95%CI 16.6-20.2 vs. 21.1% 95%CI 19.2-23.0 and sHR 0.86 95%CI 0.74-0.99, P =0.039) ( Figure ). Conclusion: Although over half of patients received multiple imaging tests within 3 months post-PVI for claudication, extensive imaging beyond ABI follow-up, was not associated with reintervention risk, which remained high with 1-year rates around 20%. Future efforts should study optimal imaging strategies and cost-benefit ratios.