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BACKGROUND AND OBJECTIVE: Blood-based small molecule metabolites offer easy accessibility and hold significant potential for insights into health processes, the impact of lifestyle, and genetic variation on disease, enabling precise risk prevention. In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline. METHODS: We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. We incorporated the network structure into the identification of metabolites associated with HF to control the effect of confounding metabolites. RESULTS: We identified metabolites associated with higher and lower risk of HF incidence, such as glycine, ureidopropionic and glycocholic acids, and LPC 18:2. These associations were not confounded by the other metabolites due to uncovering the connectivity among metabolites and adjusting each association for the confounding metabolites. Examples of our findings include the direct influence of asparagine on glycine, both of which were inversely associated with HF. These two metabolites were influenced by polygenic factors and only essential amino acids, which are not synthesized in the human body and are obtained directly from the diet. CONCLUSION: Metabolites may play a critical role in linking genetic background and lifestyle factors to HF incidence. Revealing the underlying connectivity of metabolites associated with HF strengthens the findings and facilitates studying complex conditions like HF.
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Insuficiência Cardíaca , Metabolômica , Insuficiência Cardíaca/metabolismo , Humanos , Metabolômica/métodos , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Metaboloma , Idoso , Redes e Vias MetabólicasRESUMO
In calcific aortic valve disease (CAVD), mechanosensitive valvular cells respond to fibrosis- and calcification-induced tissue stiffening, further driving pathophysiology. No pharmacotherapeutics are available to treat CAVD because of the paucity of (i) appropriate experimental models that recapitulate this complex environment and (ii) benchmarking novel engineered aortic valve (AV)-model performance. We established a biomaterial-based CAVD model mimicking the biomechanics of the human AV disease-prone fibrosa layer, three-dimensional (3D)-bioprinted into 96-well arrays. Liquid chromatography-tandem mass spectrometry analyses probed the cellular proteome and vesiculome to compare the 3D-bioprinted model versus traditional 2D monoculture, against human CAVD tissue. The 3D-bioprinted model highly recapitulated the CAVD cellular proteome (94% versus 70% of 2D proteins). Integration of cellular and vesicular datasets identified known and unknown proteins ubiquitous to AV calcification. This study explores how 2D versus 3D-bioengineered systems recapitulate unique aspects of human disease, positions multiomics as a technique for the evaluation of high throughput-based bioengineered model systems, and potentiates future drug discovery.
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Estenose da Valva Aórtica , Valva Aórtica , Valva Aórtica/patologia , Calcinose , Humanos , Valva Aórtica/química , Valva Aórtica/metabolismo , Proteômica , Proteoma/metabolismo , Estenose da Valva Aórtica/etiologia , Estenose da Valva Aórtica/metabolismo , Células CultivadasRESUMO
Objectives: It is uncertain whether concurrent mitral valve repair or replacement for moderate or greater secondary mitral regurgitation at the time of coronary artery bypass graft or aortic valve replacement surgery improves long-term survival. Methods: Patients undergoing coronary artery bypass graft and/or aortic valve replacement surgery with moderate or greater secondary mitral regurgitation were reviewed. The effect of concurrent mitral valve repair or replacement upon long-term mortality was assessed while accounting for patient and operative characteristics and mitral regurgitation severity. Results: Of 1,515 patients, 938 underwent coronary artery bypass graft or aortic valve replacement surgery alone and 577 underwent concurrent mitral valve repair or replacement. Concurrent mitral valve repair or replacement did not alter the risk of postoperative mortality for patients with moderate mitral regurgitation (hazard ratio = 0.93; 0.75-1.17) or more-than-moderate mitral regurgitation (hazard ratio = 1.09; 0.74-1.60) in multivariable regression. Patients with more-than-moderate mitral regurgitation undergoing coronary artery bypass graft-only surgery had a survival advantage from concurrent mitral valve repair or replacement in the first two postoperative years (P = 0.028) that did not persist beyond that time. Patients who underwent concurrent mitral valve repair or replacement had a higher rate of later mitral valve operation or reoperation over the five subsequent years (1.9% vs. 0.2%; P = 0.0014) than those who did not. Conclusions: These observations suggest that mitral valve repair or replacement for more-than-moderate mitral regurgitation at the time of coronary artery bypass grafting may be reasonable in a suitably selected coronary artery bypass graft population but not for aortic valve replacement, with or without coronary artery bypass grafting. Our findings are supportive of 2021 European guidelines that severe secondary mitral regurgitation "should" or be "reasonabl[y]" intervened upon at the time of coronary artery bypass grafting but do not support 2020 American guidelines for performing mitral valve repair or replacement concurrent with aortic valve replacement, with or without coronary artery bypass grafting.
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BACKGROUND: Patients undergoing cardiac surgery are prone to numerous complications. Increased vascular permeability may be associated with morbidity and mortality due to hemodynamic instability, fluid overload, and edema formation. We hypothesized that markers of endothelial injury and inflammation are associated with capillary leak, ultimately increasing the risk of postoperative complications. METHODS: In this prospective, observational, multidisciplinary cohort study at our tertiary academic medical center, we recruited 405 cardiac surgery patients. Patients were assessed daily using body impedance electrical analysis, ultrasound, sublingual intravital microscopy, and analysis of serum biomarkers. Multivariable models, as well as machine learning, were used to study the association of angiopoietin-2 with extracellular water as well as common complications after cardiac surgery. RESULTS: The majority of patients underwent coronary artery bypass grafting, valvular, or aortic surgeries. Across the groups, extracellular water increased postoperatively (20 ± 6 preoperatively to 29 ± 7L on postoperative day 2; P < 0.001). Concomitantly, the levels of the biomarker angiopoietin-2 rose, showing a strong correlation based on the time points of measurements (r = 0.959, P = 0.041). Inflammatory (IL-6, IL-8, CRP) and endothelial biomarkers (VE-Cadherin, syndecan-1, ICAM-1) suggestive of capillary leak were increased. After controlling for common risk factors of edema formation, we found that an increase of 1 ng/mL in angiopoietin-2 was associated with a 0.24L increase in extracellular water (P < 0.001). Angiopoietin-2 showed increased odds for the development of acute kidney injury (OR 1.095 [95% CI 1.032, 1.169]; P = 0.004) and was furthermore associated with delayed extubation, longer time in the ICU, and a higher chance of prolonged dependence on vasoactive medication. Machine learning predicted postoperative complications when capillary leak was added to standard risk factors. CONCLUSIONS: Capillary leak and subsequent edema formation are relevant problems after cardiac surgery. Levels of angiopoietin-2 in combination with extracellular water show promising potential to predict postoperative complications after cardiac surgery. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry (DRKS No. 00017057), Date of registration 05/04/2019, www.drks.de.
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BACKGROUND: Fewer than 50% of patients who develop aortic valve calcification have concomitant atherosclerosis, implying differential pathogenesis. Although circulating extracellular vesicles (EVs) act as biomarkers of cardiovascular diseases, tissue-entrapped EVs are associated with early mineralization, but their cargoes, functions, and contributions to disease remain unknown. METHODS: Disease stage-specific proteomics was performed on human carotid endarterectomy specimens (n=16) and stenotic aortic valves (n=18). Tissue EVs were isolated from human carotid arteries (normal, n=6; diseased, n=4) and aortic valves (normal, n=6; diseased, n=4) by enzymatic digestion, (ultra)centrifugation, and a 15-fraction density gradient validated by proteomics, CD63-immunogold electron microscopy, and nanoparticle tracking analysis. Vesiculomics, comprising vesicular proteomics and small RNA-sequencing, was conducted on tissue EVs. TargetScan identified microRNA targets. Pathway network analyses prioritized genes for validation in primary human carotid artery smooth muscle cells and aortic valvular interstitial cells. RESULTS: Disease progression drove significant convergence (P<0.0001) of carotid artery plaque and calcified aortic valve proteomes (2318 proteins). Each tissue also retained a unique subset of differentially enriched proteins (381 in plaques; 226 in valves; q<0.05). Vesicular gene ontology terms increased 2.9-fold (P<0.0001) among proteins modulated by disease in both tissues. Proteomics identified 22 EV markers in tissue digest fractions. Networks of proteins and microRNA targets changed by disease progression in both artery and valve EVs revealed shared involvement in intracellular signaling and cell cycle regulation. Vesiculomics identified 773 proteins and 80 microRNAs differentially enriched by disease exclusively in artery or valve EVs (q<0.05); multiomics integration found tissue-specific EV cargoes associated with procalcific Notch and Wnt signaling in carotid arteries and aortic valves, respectively. Knockdown of tissue-specific EV-derived molecules FGFR2, PPP2CA, and ADAM17 in human carotid artery smooth muscle cells and WNT5A, APP, and APC in human aortic valvular interstitial cells significantly modulated calcification. CONCLUSIONS: The first comparative proteomics study of human carotid artery plaques and calcified aortic valves identifies unique drivers of atherosclerosis versus aortic valve stenosis and implicates EVs in advanced cardiovascular calcification. We delineate a vesiculomics strategy to isolate, purify, and study protein and RNA cargoes from EVs entrapped in fibrocalcific tissues. Integration of vesicular proteomics and transcriptomics by network approaches revealed novel roles for tissue EVs in modulating cardiovascular disease.
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Estenose da Valva Aórtica , Aterosclerose , Calcinose , Vesículas Extracelulares , MicroRNAs , Humanos , Valva Aórtica/patologia , Estenose da Valva Aórtica/patologia , Multiômica , Calcinose/metabolismo , Células Cultivadas , MicroRNAs/metabolismo , Aterosclerose/patologia , Via de Sinalização Wnt , Vesículas Extracelulares/metabolismoRESUMO
OBJECTIVES: To determine whether preoperative (preop) tricuspid regurgitation (TR) severity grade was associated with postoperative mortality, to examine the correlation between pre-op and intraoperative (intraop) TR grades, and to understand which TR grade had better prognostic predictability in cardiac surgery patients. DESIGN: Retrospective. SETTING: Single institution. PARTICIPANTS: Patients. INTERVENTIONS: Preop and intraop echocardiography TR grades of 4,232 patients who had undergone cardiac surgeries between 2004 and 2014 were examined. MEASUREMENTS AND MAIN RESULTS: Kaplan-Meier curves and Cox proportional hazard models were used to determine the association between TR grades and the primary endpoint of all-cause mortality. The Wilcoxon signed-rank test and Spearman's rank correlation were analyzed to assess the similarity and correlation between preop and intraop-grade pairs. Multivariate logistic regression models of the area under the curve characteristics were compared for prognostic implications. Kaplan-Meier curves demonstrated a strong relationship between preop grades and survival. Multivariate models showed significantly increased mortality starting at mild preop TR (mild TR: hazard ratio [HR] 1.24; 95% CI 1.05-1.46, p = 0.013; moderate TR: HR 1.60; 95% CI 1.05-1.97, p < 0.001; severe TR: HR 2.50; 95% CI 1.74-3.58, p < 0.001). Preop TR grades were mostly higher than intraop grades. Spearman's correlation was 0.55 (p < 0.001). The area under the curves of preop and intraop TR-based models were almost identical (0.704 v 0.702 1-year mortality and 0.704 v 0.700 2-year mortality). CONCLUSIONS: The authors found that echocardiographically-determined preop TR grade at the time of surgical planning was associated with long-term mortality, starting even at a mild grade. Preop grades were higher than intraop grades, with a moderate correlation. Preop and intraop grades exhibited similar prognostic implications.
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Procedimentos Cirúrgicos Cardíacos , Insuficiência da Valva Tricúspide , Humanos , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/cirurgia , Estudos Retrospectivos , Modelos de Riscos Proporcionais , Prognóstico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Resultado do Tratamento , Índice de Gravidade de DoençaRESUMO
Importance: Nonsyndromic bicuspid aortic valve (nsBAV) is the most common congenital heart valve malformation. BAV has a heritable component, yet only a few causative genes have been identified; understanding BAV genetics is a key point in developing personalized medicine. Objective: To identify a new gene for nsBAV. Design, Setting, and Participants: This was a comprehensive, multicenter, genetic association study based on candidate gene prioritization in a familial cohort followed by rare and common association studies in replication cohorts. Further validation was done using in vivo mice models. Study data were analyzed from October 2019 to October 2022. Three cohorts of patients with BAV were included in the study: (1) the discovery cohort was a large cohort of inherited cases from 29 pedigrees of French and Israeli origin; (2) the replication cohort 1 for rare variants included unrelated sporadic cases from various European ancestries; and (3) replication cohort 2 was a second validation cohort for common variants in unrelated sporadic cases from Europe and the US. Main Outcomes and Measures: To identify a candidate gene for nsBAV through analysis of familial cases exome sequencing and gene prioritization tools. Replication cohort 1 was searched for rare and predicted deleterious variants and genetic association. Replication cohort 2 was used to investigate the association of common variants with BAV. Results: A total of 938 patients with BAV were included in this study: 69 (7.4%) in the discovery cohort, 417 (44.5%) in replication cohort 1, and 452 (48.2%) in replication cohort 2. A novel human nsBAV gene, MINDBOMB1 homologue MIB1, was identified. MINDBOMB1 homologue (MIB1) is an E3-ubiquitin ligase essential for NOTCH-signal activation during heart development. In approximately 2% of nsBAV index cases from the discovery and replication 1 cohorts, rare MIB1 variants were detected, predicted to be damaging, and were significantly enriched compared with population-based controls (2% cases vs 0.9% controls; P = .03). In replication cohort 2, MIB1 risk haplotypes significantly associated with nsBAV were identified (permutation test, 1000 repeats; P = .02). Two genetically modified mice models carrying Mib1 variants identified in our cohort showed BAV on a NOTCH1-sensitized genetic background. Conclusions and Relevance: This genetic association study identified the MIB1 gene as associated with nsBAV. This underscores the crucial role of the NOTCH pathway in the pathophysiology of BAV and its potential as a target for future diagnostic and therapeutic intervention.
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Doença da Válvula Aórtica Bicúspide , Transdução de Sinais , Ubiquitina-Proteína Ligases , Receptores Notch/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Estudos de Associação Genética , HumanosRESUMO
BACKGROUND: Conflicting evidence exists regarding the risks and benefits of inotropic therapies during cardiac surgery, and the extent of variation in clinical practice remains understudied. Therefore, the authors sought to quantify patient-, anesthesiologist-, and hospital-related contributions to variation in inotrope use. METHODS: In this observational study, nonemergent adult cardiac surgeries using cardiopulmonary bypass were reviewed across a multicenter cohort of academic and community hospitals from 2014 to 2019. Patients who were moribund, receiving mechanical circulatory support, or receiving preoperative or home inotropes were excluded. The primary outcome was an inotrope infusion (epinephrine, dobutamine, milrinone, dopamine) administered for greater than 60 consecutive min intraoperatively or ongoing upon transport from the operating room. Institution-, clinician-, and patient-level variance components were studied. RESULTS: Among 51,085 cases across 611 attending anesthesiologists and 29 hospitals, 27,033 (52.9%) cases received at least one intraoperative inotrope, including 21,796 (42.7%) epinephrine, 6,360 (12.4%) milrinone, 2,000 (3.9%) dobutamine, and 602 (1.2%) dopamine (non-mutually exclusive). Variation in inotrope use was 22.6% attributable to the institution, 6.8% attributable to the primary attending anesthesiologist, and 70.6% attributable to the patient. The adjusted median odds ratio for the same patient receiving inotropes was 1.73 between 2 randomly selected clinicians and 3.55 between 2 randomly selected institutions. Factors most strongly associated with increased likelihood of inotrope use were institutional medical school affiliation (adjusted odds ratio, 6.2; 95% CI, 1.39 to 27.8), heart failure (adjusted odds ratio, 2.60; 95% CI, 2.46 to 2.76), pulmonary circulation disorder (adjusted odds ratio, 1.72; 95% CI, 1.58 to 1.87), loop diuretic home medication (adjusted odds ratio, 1.55; 95% CI, 1.42 to 1.69), Black race (adjusted odds ratio, 1.49; 95% CI, 1.32 to 1.68), and digoxin home medication (adjusted odds ratio, 1.48; 95% CI, 1.18 to 1.86). CONCLUSIONS: Variation in inotrope use during cardiac surgery is attributable to the institution and to the clinician, in addition to the patient. Variation across institutions and clinicians suggests a need for future quantitative and qualitative research to understand variation in inotrope use affecting outcomes and develop evidence-based, patient-centered inotrope therapies.
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Procedimentos Cirúrgicos Cardíacos , Cardiotônicos , Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Contração Miocárdica/efeitos dos fármacos , Cardiotônicos/uso terapêutico , Epinefrina/uso terapêutico , Dopamina/uso terapêutico , Dobutamina/uso terapêutico , Milrinona/uso terapêutico , Cuidados IntraoperatóriosRESUMO
INTRODUCTION: Dozens of multivariable prediction models for atrial fibrillation after cardiac surgery (AFACS) have been published, but none have been incorporated into regular clinical practice. One of the reasons for this lack of adoption is poor model performance due to methodological weaknesses in model development. In addition, there has been little external validation of these existing models to evaluate their reproducibility and transportability. The aim of this systematic review is to critically appraise the methodology and risk of bias of papers presenting the development and/or validation of models for AFACS. METHODS: We will identify studies that present the development and/or validation of a multivariable prediction model for AFACS through searches of PubMed, Embase and Web of Science from inception to 31 December 2021. Pairs of reviewers will independently extract model performance measures, assess methodological quality and assess risk of bias of included studies using extraction forms adapted from a combination of the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist and the Prediction Model Risk of Bias Assessment Tool. Extracted information will be reported by narrative synthesis and descriptive statistics. ETHICS AND DISSEMINATION: This systemic review will only include published aggregate data, so no protected health information will be used. Study findings will be disseminated through peer-reviewed publications and scientific conference presentations. Further, this review will identify weaknesses in past AFACS prediction model development and validation methodology so that subsequent studies can improve upon prior practices and produce a clinically useful risk estimation tool. PROSPERO REGISTRATION NUMBER: CRD42019127329.
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Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Humanos , Fibrilação Atrial/etiologia , Reprodutibilidade dos Testes , Revisões Sistemáticas como Assunto , Viés , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Literatura de Revisão como AssuntoRESUMO
OBJECTIVE: To develop a validated clinical prognostic model to determine the risk of atrial fibrillation after cardiac surgery as part of the PARADISE project (NIHR131227). METHODS: Prospective cohort study with linked electronic health records from a cohort of 5.6 million people in the United Kingdom Clinical Practice Research Datalink from 1998 to 2016. For model development, we considered a priori candidate predictors including demographics, medical history, medications, and clinical biomarkers. We evaluated associations between covariates and the AF incidence at the end of follow-up using logistic regression with the least absolute shrinkage and selection operator. The model was validated internally with the bootstrap method; subsequent performance was examined by discrimination quantified with the c-statistic and calibration assessed by calibration plots. The study follows TRIPOD guidelines. RESULTS: Between 1998 and 2016, 33,464 patients received cardiac surgery among the 5,601,803 eligible individuals. The final model included 13-predictors at baseline: age, year of index surgery, elevated CHA2DS2-VASc score, congestive heart failure, hypertension, acute coronary syndromes, mitral valve disease, ventricular tachycardia, valve surgery, receiving two combined procedures (e.g., valve replacement + coronary artery bypass grafting), or three combined procedures in the index procedure, statin use, and ethnicity other than white or black (statins and ethnicity were protective). This model had an optimism-corrected C-statistic of 0.68 both for the derivation and validation cohort. Calibration was good. CONCLUSIONS: We developed a model to identify a group of individuals at high risk of AF and adverse outcomes who could benefit from long-term arrhythmia monitoring, risk factor management, rhythm control and/or thromboprophylaxis.
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Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Tromboembolia Venosa , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Estudos de Coortes , Prognóstico , Estudos Prospectivos , Anticoagulantes , Medição de Risco/métodos , Tromboembolia Venosa/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fatores de RiscoRESUMO
Acute postoperative pain (APOP) is often evaluated through granular parameters, though monitoring postoperative pain using trends may better describe pain state. We investigated acute postoperative pain trajectories in cardiac surgical patients to identify subpopulations of pain resolution and elucidate predictors of problematic pain courses. We examined retrospective data from 2810 cardiac surgical patients at a single center. The k-means algorithm for longitudinal data was used to generate clusters of pain trajectories over the first 5 postoperative days. Patient characteristics were examined for association with cluster membership using ordinal and multinomial logistic regression. We identified 3 subgroups of pain resolution after cardiac surgery: 37.7% with good resolution, 44.2% with moderate resolution, and 18.2% exhibiting poor resolution. Type I diabetes (2.04 [1.00-4.16], p = 0.05), preoperative opioid use (1.65 [1.23-2.22], p = 0.001), and illicit drug use (1.89 [1.26-2.83], p = 0.002) elevated risk of membership into worse pain trajectory clusters. Female gender (1.72 [1.30-2.27], p < 0.001), depression (1.60 [1.03-2.50], p = 0.04) and chronic pain (3.28 [1.79-5.99], p < 0.001) increased risk of membership in the worst pain resolution cluster. This study defined 3 APOP resolution subgroups based on pain score trend after cardiac surgery and identified factors that predisposed patients to worse resolution. Patients with moderate or poor pain trajectory consumed more opioids and received them for longer before discharge. Future studies are warranted to determine if altering postoperative pain monitoring and management improve postoperative course of patients at risk of moderate or poor pain resolution.
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BACKGROUND: Cardiac valvular disease affects millions of people worldwide and is a major cause of morbidity and mortality. Female patients have been shown to experience inferior clinical outcomes after nonvalvular cardiac surgery, but recent data are limited regarding open valve surgical cohorts. The primary objective of our study was to assess whether female sex is associated with increased in-hospital mortality after open cardiac valve operations. METHODS: Utilizing the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID), we conducted a retrospective cohort study of patients who underwent open cardiac valve surgery from 2007 to 2018 in Washington, Maryland, Kentucky, and Florida; from 2007 to 2011 in California; and from 2007 to 2016 in New York. The primary objective of this study was to estimate the confounder-adjusted association between sex and in-hospital mortality (as recorded and coded by SID HCUP) after open cardiac valve surgery. We used multilevel multivariable models to account for potential confounders, including intrahospital practice patterns. RESULTS: A total of 272,954 patients (108,443 women; 39.73% of sample population with mean age of 67.6 ± 14.3 years) were included in our analysis. The overall mortality rates were 3.8% for male patients and 5.1% for female patients. The confounder-adjusted odds ratio (OR) for in-hospital mortality for female patients compared to male patients was 1.41 (95% confidence interval [CI], 1.35-1.47; P < .001). When stratifying by surgical type, female patients were also at increased odds of in-hospital mortality ( P < .001) in populations undergoing aortic valve replacement (adjusted OR [aOR], 1.38; 95% CI, 1.25-1.52); multiple valve surgery (aOR, 1.38; 95% CI, 1.22-1.57); mitral valve replacement (aOR, 1.22; 95% CI, 1.12 - 1.34); and valve surgery with coronary artery bypass grafting (aOR, 1.64; 95% CI, 1.54 - 1.74; all P < .001). Female patients did not have increased odds of in-hospital mortality in populations undergoing mitral valve repair (aOR, 1.26; 95% CI, 0.98 - 1.64; P = .075); aortic valve repair (aOR, 0.87; 95% CI, 0.67 - 1.14; P = .32); or any other single valve repair (aOR, 1.10; 95% CI, 0.82 - 1.46; P = .53). CONCLUSIONS: We found an association between female patients and increased confounder-adjusted odds of in-hospital mortality after open cardiac valve surgery. More research is needed to better understand and categorize these important outcome differences. Future research should include observational analysis containing granular and complete patient- and surgery-specific data.
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Implante de Prótese de Valva Cardíaca , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Mortalidade Hospitalar , Estudos Retrospectivos , Fatores de Risco , Caracteres Sexuais , Resultado do TratamentoRESUMO
COVID-19 is associated with significant extrapulmonary symptoms. Myocardial involvement has been described for infections with SARS-CoV-2 which may lead to an increase in morbidity and mortality. The objective of our study was to investigate the association of COVID-19 and atrial fibrillation (AF) or atrial flutter (AFl) in hospitalized patients. This retrospective study used electronic medical records to detect patients with COVID-19 and their comorbidities within the Mass General Brigham hospital system. All patients ≥ 18 years who were hospitalized and received a PCR test for SARS-CoV-2 were screened for inclusion as well as patients from a pre-pandemic cohort. We matched on common risk factors for AF and then used multivariable logistic regression to estimate the odds for AF or AFl. Of 78,725 patients eligible for analysis, 11,004 COVID-19 negative patients were matched to 3,090 COVID-19 positive patients and 5005 pre-pandemic patients were matched to 2283 COVID-19 positive patients. After adjusting for demographics and comorbidities, COVID-19 positive patients had 1.19 times the odds (95% CI 1.00, 1.41) of developing AF compared to COVID-19 negative patients and 1.57 times the odds (95% CI 1.23, 2.00) of developing AF compared to pre-pandemic patients. Our study demonstrated an increased risk for AF, directing the attention for improved screening and treatment regimens for the sequelae of COVID-19. While COVID-19 continues to affect many people around the world, AF may be a significant cause for morbidity and mortality. Adequate detection and treatment of AF is essential to reduce the burden of disease.
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Fibrilação Atrial , Flutter Atrial , COVID-19 , Fibrilação Atrial/diagnóstico , COVID-19/epidemiologia , Humanos , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2RESUMO
AIMS: Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder. METHODS AND RESULTS: We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors. CONCLUSION: We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-ß signalling molecules and spectrin ß. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention.
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Prolapso da Valva Mitral , Adulto , Loci Gênicos/genética , Estudo de Associação Genômica Ampla , Humanos , Proteínas de Ligação a TGF-beta Latente/genética , Prolapso da Valva Mitral/genética , Proteômica , Fatores de RiscoRESUMO
Atrial fibrillation after cardiac surgery (AFACS) is a serious postoperative complication. There is significant research interest in this field but also relevant heterogeneity in reported AFACS definitions and approaches used for its identification. Few data exist on the extent of this variation in clinical studies. The authors reviewed the literature since 2001 and included manuscripts reporting outcomes of AFACS in adults. They excluded smaller studies and studies in which patients did not undergo a sternotomy. The documented protocol in each manuscript was analyzed according to six different categories to determine how AFACS was defined, which techniques were used to identify it, and the inclusion and/or exclusion criteria. They also noted when a category was not described in the documented protocol. The authors identified 302 studies, of which 92 were included. Sixty-two percent of studies were randomized controlled trials. There was significant heterogeneity in the manuscripts, including the exclusion of patients with preoperative AF, the definition and duration of AF needed to meet the primary endpoint, the type of screening approach (continuous, episodic, or opportunistic), the duration of monitoring during the study period in days, the diagnosis with predefined electrocardiogram criteria, and the requirement for independent confirmation by study investigators. Furthermore, the definitions of these criteria frequently were not described. Consistent reporting standards for AFACS research are needed to advance scientific progress in the field. The authors here propose pragmatic standards for trial design and reporting standards. These include adequate sample size estimation, a clear definition of the AFACS endpoints, and a protocol for AFACS detection.
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Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Adulto , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Eletrocardiografia , Humanos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: In recent years, increased attention has turned toward the risk of chronic opioid use after surgery. In this nationwide cohort study, we examined the rate of new persistent opioid use after cardiac surgery by sternotomy. METHODS: All opioid-naive patients undergoing heart surgery by sternotomy from 2005 to 2018 in Iceland were included in the study. Naivety was defined as not filling an opioid prescription within 6 months before surgery. Persistent opioid use was defined as filling at least 1 opioid prescription during the first 90 days after surgery and another 90 to 180 days after the operation. In addition to estimating the incidence of new persistent opioid use, differences in patient characteristics, survival, and readmission rates were compared between the group with and without new persistent opioid use. RESULTS: Of 1227 patients who underwent cardiac surgery by sternotomy during the study period, 925 were included in the study. Of those, 4.6% developed new persistent opioid use. When only patients who filled an opioid prescription after surgery were included, 10.1% developed new persistent opioid use. Chronic obstructive pulmonary disease, preoperative use of nonsteroidal anti-inflammatory drugs, gabapentinoids, and nitrates were associated with increased risk for new persistent opioid use. Patients with new persistent opioid use did not have higher rates of readmission nor all-cause mortality. CONCLUSIONS: The rate of new persistent opioid use after cardiac surgery was 4.6%. Future steps should identify strategies to minimize the development of new persistent opioid use.
Assuntos
Analgésicos Opioides/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Esternotomia/efeitos adversos , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Long noncoding RNAs (lncRNAs) have been implicated in the pathogenesis of cardiovascular diseases. We aimed to identify novel lncRNAs associated with the early response to ischemia in the heart. METHODS AND RESULTS: RNA sequencing data gathered from 81 paired left ventricle samples from patients undergoing cardiopulmonary bypass was collected before and after a period of ischemia. Novel lncRNAs were validated with Oxford Nanopore Technologies long-read sequencing. Gene modules associated with an early ischemic response were identified and the subcellular location of selected lncRNAs was determined with RNAscope. A total of 2446 mRNAs, 270 annotated lncRNAs and one novel lncRNA differed in response to ischemia (adjusted p < 0.001, absolute fold change >1.2). The novel lncRNA belonged to a gene module of highly correlated genes that also included 39 annotated lncRNAs. This module associated with ischemia (Pearson correlation coefficient = -0.69, p = 1 × 10-23) and activation of cell death pathways (p < 6 × 10-9). A further nine novel cardiac lncRNAs were identified, of which, one overlapped five cis-eQTL eSNPs for the gene RWD Domain-Containing Sumoylation Enhancer (RWDD3) and was itself correlated with RWDD3 expression (Pearson correlation coefficient -0.2, p = 0.002). CONCLUSION: We have identified 10 novel lncRNAs, one of which was associated with myocardial ischemia and may have potential as a novel therapeutic target or early marker for myocardial dysfunction.