Publications by authors named "Simon Body"

Background: Bicuspid aortic valve (BAV) is the most common congenital heart defect in adults, often leading to complications such as thoracic aortic aneurysms and aortic stenosis. While BAV is frequently associated with 22q11.2 deletion syndrome (22q11.

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Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms.

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Article Synopsis
  • * Researchers analyzed whole-exome sequences from 215 families affected by EBAV, finding that 50% contained harmful gene variants related to BAV and related heart conditions.
  • * A total of 129 genetic variants were identified in 54 candidate genes associated with congenital heart issues, supporting the idea that specific rare genetic changes contribute to the severity of BAV.
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Importance: There are limited data on the association of sex with the incidence of postoperative atrial fibrillation (poAF) and subsequent long-term mortality after cardiac surgery.

Objective: To evaluate whether the incidence of poAF and associated long-term mortality after cardiac surgery differ by sex.

Design, Setting, And Participants: This retrospective cohort study was conducted at 2 tertiary care centers in Massachusetts from January 1, 2002, until October 1, 2016, with follow-up until December 1, 2022.

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Bicuspid aortic valve (BAV) is the most common congenital heart malformation in adults but can also cause childhood-onset complications. In multicenter study, we found that adults who experience significant complications of BAV disease before age 30 are distinguished from the majority of BAV cases that manifest after age 50 by a relatively severe clinical course, with higher rates of surgical interventions, more frequent second interventions, and a greater burden of congenital heart malformations. These observations highlight the need for prompt recognition, regular lifelong surveillance, and targeted interventions to address the significant health burdens of patients with early onset BAV complications.

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Bicuspid Aortic Valve (BAV) is the most common adult congenital heart lesion with an estimated population prevalence of 1%. We hypothesize that early onset complications of BAV (EBAV) are driven by specific impactful genetic variants. We analyzed whole exome sequences (WES) to identify rare coding variants that contribute to BAV disease in 215 EBAV families.

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Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms.

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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.

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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).

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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.

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Aims: Calcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored.

Methods And Results: An aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification.

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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.

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Cellular heterogeneity of aortic valves complicates the mechanistic evaluation of the calcification processes in calcific aortic valve disease (CAVD), and animal disease models are lacking. In this study, we identify a disease-driver population (DDP) within valvular interstitial cells (VICs). Through stepwise single-cell analysis, phenotype-guided omic profiling, and network-based analysis, we characterize the DDP fingerprint as CD44CD29CD59CD73CD45 and discover potential key regulators of human CAVD.

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Article Synopsis
  • Mitral valve prolapse (MVP) is a widespread heart valve disease affecting over 2% of adults, yet its genetic mechanisms are not well understood and there are no current medical treatments available.
  • A comprehensive analysis of genetic data from nearly 5,000 MVP cases and over 434,000 controls uncovered 14 genetic loci linked to MVP, along with key candidate genes that may play a role in the disorder.
  • The study introduced a polygenic risk score (PRS) for MVP, enhancing the ability to predict MVP risk and potentially guiding future patient screening and therapeutic interventions.
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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.

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Aortic valve (AV) leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance. The ECM structure is maintained by valvular interstitial cells (VICs), which reside within the leaflets. The presence of pigment produced by a melanocytic population of VICs in mice with dark coats has been generally regarded as a nuisance, as it interferes with histological analysis of the AV leaflets.

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  • Patients with bicuspid aortic valve (BAV) are at higher risk for serious heart conditions like aortic dilation and dissection.
  • This study investigated whether regular physical activity affects aortic diameter changes in pediatric BAV patients by comparing active and sedentary groups over two years.
  • Results showed no significant difference in aortic dilation between physically active and sedentary subjects, indicating that physical exercise doesn't seem to influence aortic size progression in these patients.
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Calcific aortic valve disease (CAVD) occurs when subpopulations of valve cells undergo specific differentiation pathways, promoting tissue fibrosis and calcification. Lipoprotein particles carry oxidized lipids that promote valvular disease, but low-density lipoprotein-lowering therapies have failed in clinical trials, and there are currently no pharmacological interventions available for this disease. Apolipoproteins are known promoters of atherosclerosis, but whether they possess pathogenic properties in CAVD is less clear.

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Objectives: Functional mitral regurgitation (MR) is observed with ischaemic heart disease or aortic valve disease. Assessing the value of mitral valve repair or replacement (MVR/P) is complicated by frequent discordance between preoperative transthoracic echocardiographic (pTTE) and intraoperative transoesophageal echocardiographic (iTOE) assessment of MR severity. We examined the association of pTTE and iTOE with postoperative mortality in patients with or without MR, at the time of coronary artery bypass grafting (CABG) and/or aortic valve replacement without MVR/P.

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Extracellular vesicles (EVs) including plasma membrane-derived microvesicles and endosomal-derived exosomes aggregate by unknown mechanisms, forming microcalcifications that promote cardiovascular disease, the leading cause of death worldwide. Here, we show a framework for assessing cell-independent EV mechanisms in disease by suggesting that annexin A1 (ANXA1)-dependent tethering induces EV aggregation and microcalcification. We present single-EV microarray, a method to distinguish microvesicles from exosomes and assess heterogeneity at a single-EV level.

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Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.

Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline.

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Thoracic aortic aneurysm (TAA) is the progressive enlargement of the aorta due to destructive changes in the connective tissue of the aortic wall. Aneurysm development is silent and often first manifested by the drastic events of aortic dissection or rupture. As yet, therapeutic agents that halt or reverse the process of aortic wall deterioration are absent, and the only available therapeutic recommendation is elective prophylactic surgical intervention.

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Thoracic aortic aneurysm is a typically silent disease characterized by a lethal natural history. Since the discovery of the familial nature of thoracic aortic aneurysm and dissection (TAAD) almost 2 decades ago, our understanding of the genetics of this disorder has undergone a transformative amplification. To date, at least 37 TAAD-causing genes have been identified and an estimated 30% of the patients with familial nonsyndromic TAAD harbor a pathogenic mutation in one of these genes.

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Objective: Bicuspid aortic valve is a common risk factor for thoracic aortic aneurysm and dissection. Guidelines for elective ascending aortic intervention (AAI) in bicuspid aortic valve are derived from limited evidence, and the extent of practice variation due to patient and provider characteristics is unknown. Using data from 2 large cardiovascular registries, we investigated factors that influence decisions for AAI.

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