medRxiv - Cardiovascular Medicine最新文献

{"title":"The Impact of In Utero Tobacco Exposure on Cardiovascular Disease Risk and All-cause Mortality in Adulthood: a UK Biobank Study","authors":"Yanxu Zheng, Xinyu Xiong, Jing Bao, Jingyu Liu, Jin Wang, Zixi Chen, Fang Zou, Yang Guo, Qingyao Wang, Yixuan Qiu, Zhaowei Zhu","doi":"10.1101/2024.08.19.24312279","DOIUrl":"https://doi.org/10.1101/2024.08.19.24312279","url":null,"abstract":"Abstract\u0000Aim\u0000The negative impacts of in utero tobacco exposure (IUTE) on cardiovascular disease (CVD) have been insufficiently described. This study aims to assess the association between IUTE and the risks of CVD incidence and all-cause mortality, discuss the inter-group difference based on genetic susceptibility and smoking behaviors after birth, and explore the potential mediating factors.\u0000Methods\u0000Utilizing a total of 375,024 participants from the UK Biobank, the outcomes include myocardial infarction, stroke, chronic ischemic heart disease, nonrheumatic aortic valve disorders, cardiomyopathy, heart failure, atherosclerosis, aortic aneurysm and dissection, and all-cause mortality.\u0000Results\u0000During a median follow-up period of 14.6 years, 50,434 cases of CVD were recorded. IUTE was significantly associated with increased CVD incidence (HR 1.10, 95% CI 1.08-1.12) and all-cause mortality (HR 1.11, 95% CI 1.09-1.14). Interaction effects between IUTE, smoking behaviors after birth, and genetic risk scores for CVD were observed significant (P for interaction < 0.005). The results of the cross-sectional study revealed a significant positive association between IUTE and smoking behaviors after birth (OR 1.08, 95% CI 1.06-1.09). Mediation analysis indicated that smoking behaviors (Proportion = 12.40%, P < 0.001) and HDL-c levels (Proportion = 14.20%, P < 0.001) partially mediated the IUTE-CVD relationship.\u0000Conclusions\u0000This study demonstrated that individuals with IUTE have a higher risk of developing CVD, and smoking behaviors after birth have multifaceted influence on this correlation. These findings underscore the importance of mothers avoiding smoking during pregnancy to mitigate adverse effects on their offspring.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA Sequencing of Peripheral Blood Mononuclear Cells in Patients with Single Ventricle/Hypoplastic Left Heart Syndrome","authors":"Hui-Qi Qu, Kayleigh Ostberg, Diana J Slater, Fengxiang Wang, James Snyder, Cuiping Hou, John J Connolly, Michael March, Joseph T Glessner, Charlly Kao, Hakon Hakonarson","doi":"10.1101/2024.08.20.24312290","DOIUrl":"https://doi.org/10.1101/2024.08.20.24312290","url":null,"abstract":"Background: Single ventricle and hypoplastic left heart syndrome (SV/HLHS) patients require lifelong medical monitoring and management to address potential complications and optimize their health. The consequence of SV/HLHS had detrimental effects on multiple organ systems, including on peripheral blood mononuclear cells (PBMCs) and can weaken the immune system, exacerbating the risk of infection and various cardiovascular complications.\u0000Methods: Using single-cell RNA sequencing (scRNA-seq), we studied PBMCs from 33 pediatric patients (10 females and 23 males) with SV/HLHS. By a pair-wide study design, the SV/HLHS patients were compared to 33 controls without heart diseases. Results: Four cell types account for the top 62% cumulative importance of disease effects on gene expression in different cell types, i.e., [T cells, CD4+, Th1/17], [T cells, CD4+, TFH], [NK cells], and [T cells, CD4+, Th2]. Significant sex differences were observed in [T cells, CD4+, TFH], with less prominent effects in female patients. A total of 6659 genes in different cell types were significantly differentially expressed (DE). Hierarchical clustering by WGCNA analysis of the DE genes revealed that DE genes in NK cells are most closely related to those in SV/HLHS. A total of 822 genes showed cell specific DE with opposite directions in different cell types, highlighting overrepresented MYC and IFN-γ activity in T cell and NK cell populations, as well as underrepresentation in monocytes and Treg cells. Conclusion: This study elucidates the complex transcriptome landscape in PBMCs in patients with SV/HLHS, emphasizing the differential impacts on various cell types. New insights are gained into the precise modulation of MYC and IFN-γ activity in SV/HLHS, which may help balance immune responses and reduce harmful inflammation, and promote effective tissue repair and infection control.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 Damages Cardiomyocytes Mitochondria and Implicates Long COVID-associated Cardiovascular Manifestations","authors":"Wenliang Che, Shuai Guo, Yanqun Wang, Xiaohua Wan, Bingyu Tan, Hailing Li, Jiasuer Ailipu, Mengyun Zhu, Zesong Chen, Peiyao Li, Zhaoyong Zhang, Yiliang Wang, Xiaohan Huang, Xinsheng Wang, Jian Zhu, Xijiang Pan, Fa Zhang, Peiyi Wang, Jincun Zhao, Yawei Xu, Zheng Liu","doi":"10.1101/2024.08.18.24311961","DOIUrl":"https://doi.org/10.1101/2024.08.18.24311961","url":null,"abstract":"Our study investigates the persistent cardiovascular symptoms observed in individuals long after contracting SARS-CoV-2, a condition commonly referred to as ?Long COVID?, which has significantly affected millions globally. We meticulously describe the cardiovascular outcomes in five patients, encompassing a range of severe conditions such as sudden cardiac death during exercise, coronary atherosclerotic heart disease, acute inferior myocardial infarction, and acute myocarditis. All five patients were diagnosed with myocarditis, confirmed through endomyocardial biopsy and histochemical staining, which identified inflammatory cell infiltration in their heart tissue. Crucially, electron microscopy revealed widespread mitochondrial vacuolations and the presence of myofilament degradation within the cardiomyocytes of these patients. These findings were mirrored in SARS-CoV-2-infected mice, suggesting a potential underlying cellular mechanism for the cardiac effects associated with Long COVID. Our report sheds light on the cardiovascular implications of Long COVID and underscores the importance of further research to understand its cellular underpinnings.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALDH2/eIF3E Interaction Modulates Protein Translation Critical for Cardiomyocyte Ferroptosis in Acute Myocardial Ischemia Injury","authors":"Xin Chen, Xiujian Yu, Xiaodong Xu, Rui Li, Ningning Liang, Lili Zhang, Luxiao Li, Jingyu Zhang, Mingyao Zhou, Tongwei Lv, Haoran Ma, Yongqiang Wang, Yanwen Ye, Chunzhao Yin, Shiting Chen, Hui Huang, Jinwei Tian, Aijun Sun, Weiyuan Wang, Dewen Yan, Pan Li, Huang-Tian Yang, Shanshan Zhong, Huiyong Yin","doi":"10.1101/2024.08.19.24312276","DOIUrl":"https://doi.org/10.1101/2024.08.19.24312276","url":null,"abstract":"Background: As an iron-dependent form of regulated cell death caused by lipid peroxidation, ferroptosis has been implicated in ischemic injury but the underlying mechanisms in acute myocardial infarction (AMI) remain poorly defined. Acetaldehyde dehydrogenase 2 (ALDH2) catalyzes detoxification of lipid aldehydes derived from lipid peroxidation and acetaldehydes from alcohol consumption. The Glu504Lys polymorphism of ALDH2 (rs671, ALDH2 *2), affecting around 8% world population and 40% East Asians, is associated with increased risk of MI. This study aims to investigate the role of ALDH2 and ferroptosis in MI.\u0000Methods: A Chinese cohort of 177 acute heart failure patients with ALDH2 wild type and ALDH2 *2 were enrolled. MI mouse model of left anterior descending coronary artery ligation (LAD) was conducted on wild type, ALDH2 *2, and mice with cardiomyocyte-specific knock down of eukaryotic translation initiation factor 3 subunit E (eIF3E) by adeno-associated virus. The lipid peroxidation products were measured by mass spectrometry-based lipidomics and metabolomics in human plasma and mouse serum samples as well as in mouse heart tissues. Results: Human ALDH2 *2 carriers exhibit more severe heart failure post-AMI with features of ferroptosis in blood samples through lipidomic analysis, including increased levels of multiple classes of oxidized phospholipids, and decreased levels of antioxidants, such as Coenzyme Q-10 (Co-Q10) and tetrahydrobiopterin (BH4). Similar features were observed in MI mouse models of ALDH2 *2, whereas ferroptosis inhibition by Fer-1 significantly improved heart functions and reversed ferroptosis markers. Importantly, ALDH2 *2 led to significantly decreased protein levels of ALDH2, whereas ferroptosis related proteins including Transferrin receptor (TFRC), Acyl-CoA synthetase long chain family member 4 (ACSL4), and Heme oxygenase 1 (HMOX1) were upregulated specifically in the infarct heart tissues. Mechanistically, ALDH2 physically interacted with eIF3E to modulate translation of critical proteins involved in ferroptosis, and ALDH2 deficiency in ALDH2 *2 mutant predisposes cardiomyocytes to ferroptosis by promoting Tfrc/Acsl4/Hmox1 translation. Consistently, cardiomyocytes-specific eIF3E knock down restored ALDH2 *2 cardiac function by attenuating ferroptosis in MI.\u0000Conclusions: ALDH2 *2 aggravates acute heart failure in MI through promoting cardiomyocytes ferroptosis, and targeting ferroptosis may be a potential therapeutic target for treating AMI, especially for ALDH2 *2 carriers.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Expression of MTSS1 Increases Sarcomere Number and Improves Contractility in Select Forms of Monogenic DCM","authors":"Hannah Kleppe, Anastasia Budan, Lucas Zhang, Marie Majetic, Reva Shenwai, Alan Levinson, Olga Cisne-Thompson, Farshad Farshidifar, Jonathan Tsui, Sylwia Figarska, Timothy Hoey, James Priest, Rebecca Slater","doi":"10.1101/2024.08.14.24311020","DOIUrl":"https://doi.org/10.1101/2024.08.14.24311020","url":null,"abstract":"Background: The I-bar protein MTSS1 is a known modifier of heart failure and contractile phenotypes but its role in modulating contractile dysfunction in genetic forms of Mendelian dilated cardiomyopathy (DCM) is not known. Methods: The potential role of cardiac MTSS1 in TTN DCM was explored using time-to-event models in observational human datasets. Using induced siRNA and mutant forms of pluripotent stem cell cardiomyocytes (iPSC-CMs) the impact of siRNA knockdown of MTSS upon sarcomere and Cardiomyocyte biology was assessed via quantitative high-content microscopy, and the impact and mechanism of MTSS1 knockdown upon contractility was assessed using engineered heart tissues (EHTs). Results: Amongst individuals affected with TTN DCM, a variant conferring lower cardiac levels of MTSS1 was associated with significantly improved event-free survival from cardiovascular death or heart transplant (HR 0.29, p=0.0016). Knockdown of MTSS1 by siRNA significantly improved the appearance of iPSC-CM models of TTN (p=2.9e-06), CSRP3 (p=3.1e-14), and RBM20 (p=4.4e-04) DCM as assessed by quantitative microscopy. Correspondingly, siRNA knockdown of MTSS1 increased contractility in EHT models of TTN DCM (p=0.003), CSRP3 DCM (p=0.008), and RBM20 DCM (p<2e-16). Across all genetic backgrounds, knockdown of MTSS1 was observed to increase the number of sarcomeres (p<0.0001), and in co-immunoprecipitation experiments MTSS1 physically interacts with MYO18A a key determinant of early sarcomere formation. Knockdown of MTSS1 resulted in increased transcription of MYH7 (0.29 log2FC, p=2.9e-06) along with other sarcomere genes. Conclusions: In iPSC-CMs Knockdown of MTSS1 by siRNA increased number of sarcomeres and was observed to increase twitch force in select in vitro models, suggesting MTSS1 may have a previously unrecognized role in modulating sarcomere production or turnover. Human observational and iPSC-CM experimental data supports the hypothesis that reduced expression of MTSS1 may be beneficial in Mendelian DCM caused by TTN, RBM20, and CSRP3.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"40 4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac MRI Phasic Assessment of Strain in Right Ventricular Dysfunction","authors":"Alexandra Janowski, Finley Mueller, Shreya Agarwal, Scott H Visovatti, Rebecca R Vanderpool","doi":"10.1101/2024.08.19.24312280","DOIUrl":"https://doi.org/10.1101/2024.08.19.24312280","url":null,"abstract":"Background: RV strain associates with mortality in pulmonary hypertension (PH) but time-resolved strain is not typically assessed. The aim was to evaluate phasic changes in RV strain using cardiac magnetic resonance (CMR) images. We hypothesized that phasic changes in ejection and filling RV strain significantly associate with outcomes in PH. Methods: Participants were identified from the Ohio State University CMR PH registry (n=96). RV endocardial areas were segmented from 4-chamber CMR Cine images. Time-resolved strains were calculated for RV global, free wall and septal strain. Ventricular dynamics were assessed during the ejection, early filling and late filling cardiac phases to quantify phasic changes in function. RV contractility, afterload and diastolic stiffness were quantified using the single-beat method. Outcomes were evaluated at one year. Results: In this retrospective, single-center study, 96 participants with and without pulmonary hypertension were included. Cohort was predominately female (n=53, 55%) with elevated mean pulmonary arterial pressure (38[26-48] mmHg) and reduced RV function (RVEF: 42[31-54] %, TAPSE of 19[15-23] cm). Filling strain patterns described changes in ventricular dynamics but did not associate with RV dilation or other measures characteristic of RV dysfunction. In comparison, decreased free wall strain and increased diastolic stiffness both associated with RV dysfunction but there were no significant differences in strain patterns. Participants with strain pattern 3, decreased free wall strain or increased Eed had increased one-year mortality. When investigated together, participants with decreased free wall strain, RVEF and increased Eed had greatly reduced one-year survival. Conclusions: Assessment of phasic changes in ventricular function does provide additional pathophysiological information but assessment of strain patterns alone are not sufficient for identifying reduced function. Deep phenotyping using a combination of RV strain and diastolic stiffness is highly selective of participants with increased one-year mortality.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous Heart and Kidney Transplantation utilizing Circulatory Death Donors in the United States","authors":"Sooyun Caroline Tavolacci, Kenji Okumura, Ameesh Isath, Gabriel Rodriguez, Corazon Belisario De La Pena, Junichi Shimamura, Steven L Lansman, Suguru Ohira","doi":"10.1101/2024.08.16.24312145","DOIUrl":"https://doi.org/10.1101/2024.08.16.24312145","url":null,"abstract":"Objective: Heart transplants utilizing donors from circulatory death (DCD) allografts are rapidly growing with the potential to expand the donor pool. However, little is known about the use of DCD donors for simultaneous heart and kidney transplants (SHKT) compared to SHKT using brain death donors (DBD). Methods: From May 22, 2020, to September 30, 2023, 1,129 adult patients received SHKT (DCD, N=91 vs. DBD, N=1,038), identified using the United Network for Organ Sharing database, excluding other multi-organ transplants and re-transplants. A 1:3 ratio propensity score matching was performed using 17 recipient characteristics and 7 donor characteristics. A total of 91 DCD and 273 DBD matched cases were compared. Results: In the unmatched cohort, DCD recipients were older (DCD: 60 vs. DBD: 58 years, p=0.03) and had a lower rate of dialysis at transplant (27% vs. 40%, p=0.03) and status 1 to 2 patients (43% vs. 72%, p<.001). Donors were younger (30 vs. 32 years, p=0.02) in the DCD group. In the matched cohort, kidney delayed graft function (27% vs. 22%, p=0.29) was comparable, as were recipient survival (p=0.19), heart graft survival (p=0.19), and kidney graft survival (p=0.17). In multivariate Cox proportional hazards analysis, donor type (DCD) was not associated with an increased risk of mortality (HR=1.69, 95% Cl 0.90-3.16, p=0.10). Sub-group analysis showed that survival and freedom from graft failures were comparable between different modes of DCD recovery. The centers performing both DCD- and DBD-SHKT showed significantly shorter waitlist days with comparable transplant outcomes compared to centers that only performed DBD-SHKT. Conclusions: SHKT using DCD donors yields comparable survival and graft outcomes to those using DBD donors. These findings will guide treatment strategies for heart transplant candidates with kidney dysfunction, including the selection of donors and patients and safety net policy options.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Natural Killer Cell Subpopulations in the Blood of Single Ventricle/Hypoplastic Left Heart Syndrome Patients Using Single-Cell RNA Sequencing","authors":"Hui-Qi Qu, Kushagra Goel, Kayleigh Ostberg, Diana J Slater, Fengxiang Wang, James Snyder, Cuiping Hou, John J Connolly, Michael March, Joseph T Glessner, Charlly Kao, Hakon Hakonarson","doi":"10.1101/2024.08.18.24312189","DOIUrl":"https://doi.org/10.1101/2024.08.18.24312189","url":null,"abstract":"We utilized single-cell RNA sequencing (scRNA-seq) to examine peripheral blood mononuclear cells (PBMCs) from patients with Single Ventricle/Hypoplastic Left Heart Syndrome (SV/HLHS), and demonstrated a more pronounced correlation between gene expression in Natural Killer (NK) cells and SV/HLHS compared to other PBMC cell types. Our scRNA-seq analysis of NK cells in this study identified two distinct clusters with gene expression patterns linked to immune responsiveness and adaptation to stress. While this finding underscores the heterogeneity of NK cells, it provides new insights into fine-tuning of immune modulation that could prevent complications in SV/HLHS. Specifically, our study suggests that while NK cells in SV/HLHS are adapting to support survival in a challenging physiological environment, these adaptations may compromise their ability to manage additional stresses such as infections and inflammation.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAVI PACER: A two-step risk score for prediction of permanent pacemaker implantation after TAVI.","authors":"Alexandra Janiszewski, Julia Christina Lueg, Daniel Schulze, Benjamin Juri, Louis Morell, Maria Hajduczenia, Pierre Hennig, Aslihan Erbay, Alexander Lembcke, Stefan Markus Niehues, Ulf Landmesser, Karl Stangl, David Manuel Leistner, Henryk Dreger, Verena Tscholl","doi":"10.1101/2024.08.17.24311901","DOIUrl":"https://doi.org/10.1101/2024.08.17.24311901","url":null,"abstract":"Background: The need for permanent pacemaker implantation (PPMI) remains one of the most frequent complications after transcatheter aortic valve implantation (TAVI). This study aimed to develop a novel, two-step risk score to predict PPMI probability after TAVI and to implement it into a user-friendly website. Our risk score addresses the gap in existing data on current prosthesis generations and provides a new and clinically motivated approach to calculating the risk for PPMI.\u0000Methods: Between January 2019 and December 2020, 1039 patients underwent TAVI at our institution. We retrospectively evaluated clinical, electrocardiographic, echocardiographic, computed tomographic, and periprocedural data. Patients with prior PPMI were excluded. We developed a prediction model for the occurrence of PPMI, initially using 55 patient and procedural characteristics.\u0000Results: We included 836 patients (mean age 80.2 ± 9.1 years, 50.5% female), among whom 140 patients (16.6%) needed PPMI within 30 days after TAVI. In the first step, the TAVI PACER score calculates an individual risk for PPMI, including 14 preprocedural risk factors such as preexisting right bundle branch block, atrioventricular block, left bundle branch block, bradycardia, interventricular septum thickness in diastole, NYHA class, and aortic annulus perimeter. In the second step, intraprocedural variables are included to demonstrate how PPMI risk can vary based on the chosen valve type and implantation depth. The TAVI PACER score can predict PPMI with a sensitivity of 76% and specificity of 72% (AUC = 0.8). Conclusions: The TAVI PACER score provides a novel tool for daily clinical practice, which predicts the individual risk for PPMI after TAVI based on various patient and two procedural characteristics.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality is lowest in overweight followed by obese and morbid obese patients and is highest in cachexia compared to normal weight in patients with the diagnosis of aortic stenosis.","authors":"Mehrtash Hashemzadeh, Arman Soltani Moghadam, Saman Soltani Moghadam, Mohammad Reza Movahed","doi":"10.1101/2024.08.17.24312157","DOIUrl":"https://doi.org/10.1101/2024.08.17.24312157","url":null,"abstract":"Introduction: The obesity paradox has been seen in many cardiovascular conditions. The goal of this study was to evaluate whether it exists in patients with a diagnosis of aortic stenosis. Method: We used the Nationwide Inpatients Sample (NIS) database and ICD-10 coding for adults in different weight categories and with aortic stenosis diagnoses for 2016-2020. We evaluated the effect of weight on mortality using multivariate adjustment and the cox-regression model. Results: A total of 2,330,584 patients were diagnosed with aortic stenosis. Mortality was lowest in overweight followed by obesity and morbid obesity (1.74% vs. 2.43% vs 3.2% in comparison to normal weight mortality of 4.4%, p<0.001) and it was highest in patients with cachexia (mortality of 14.5%). After adjusting for baseline characteristics and comorbid conditions, the relation between mortality and weights remained unaltered. Multivariate adjusted odds ratios (OR) were as follows: Overweight OR 0.4, CI 0.31-0.6, p<0.001, Obesity: OR 0.64, CI 06-0.68, p<0.001, morbid obesity OR: 0.88, CI 0.83-0.94, P<0.001, Cachexia OR 3.31 CI: 3.04-3.62, p<0.001).\u0000Conclusion: Using the largest database, we found that in patients with a diagnosis of aortic stenosis, overweight followed by obesity and morbid obesity have the lowest mortality whereas cachexia has the highest mortality compared to normal-weight patients.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}