Publications by authors named "Jason C Kovacic"

Background And Aims: Clonal haematopoiesis of indeterminate potential (CHIP) has been associated with cardiovascular risk, but its prognostic relevance and mechanistic role in coronary artery disease (CAD) remains incompletely understood. This study investigated the association between CHIP and all-cause mortality in CAD and explored the cellular and molecular mechanisms, focusing on TET2 mutations.

Methods: Targeted deep sequencing of 13 CHIP driver genes in 8612 patients with angiographically confirmed CAD was performed.

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Background: Accurate classification of aortic stenosis (AS) severity remains challenging despite detailed echocardiographic assessment. Adjudication of severity is informed by subjective interpretation of aortic leaflet motion from the first image parasternal long axis (PLAX) view, but quantitative metrics of leaflet motion currently do not exist. The objectives of the study were to echocardiographically quantify aortic leaflet motion using the PLAX view and correlate motion data with Doppler-derived hemodynamic indices of disease severity, and predict significant AS using these isolated motion data.

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Coronary artery disease (CAD) is a major cause of global morbidity and mortality. Macrophages play a central role in orchestrating this disease process. In 2016, we initiated the STARNET primary blood macrophage study, followed by the multi-ethnic NGS-PREDICT primary blood macrophage study in 2018.

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Carotid stenosis causes ischemic stroke in both sexes, but the clinical presentation and plaque characteristics differ. Here we run deep single-cell sequencing of 7,690 human carotid plaque cells from male and female patients. While we found no sex differences in major cell types, we identified a predominance of the osteogenic phenotype in smooth muscle cells, immunomodulating macrophages (MPs) and endothelial cells (ECs) undergoing endothelial-to-mesenchymal transition in females.

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Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome or sudden cardiac death, primarily affecting relatively young women (median age, 51 years) without typical cardiovascular risk factors. SCAD has a genetic component, with genome-wide association studies identifying multiple risk loci. Thoracic aortic dissection (type A) shares some genetic overlap with SCAD, suggesting potential common predispositions.

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The plasma proteome is the future for diagnostic markers for common diseases, like cardiometabolic disorders (CMDs) and coronary artery disease (CAD). The reliability of these markers requires identifying their source-organ(s). We profiled 974 plasma proteins in 532 CAD-patients of the STARNET study with arterial wall, major metabolic organ, and blood transcriptomic data.

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We report a unique case involving cardiac manifestation of T-cell lymphoma and associated risk management of ventricular arrhythmia and sudden cardiac death. A 39-year-old woman presented with a syndrome consistent with fever in a returned traveler, ultimately diagnosed with stage IV peripheral T-cell lymphoma involving the myocardium with ventricular tachycardia. Management of risk of sudden cardiac death was complicated by hematological management with an antibody-drug conjugate chemotherapy regimen and later autologous stem cell transplant.

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Article Synopsis
  • Despite progress in recognizing and diagnosing spontaneous coronary artery dissection (SCAD) in the last decade, there is still limited understanding of its mechanisms, contributing factors, and effective treatments.
  • The text highlights research gaps in SCAD and suggests strategies like patient advocacy, independent registries, and specialized centers to improve clinical care and research outcomes.
  • Additionally, it presents a patient-centered clinical care and research framework developed by the SCAD Alliance and International SCAD registry as a model to enhance understanding and management of this condition.
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Background: Coronary artery disease (CAD) is a complex, heterogeneous disease with distinct etiological mechanisms. These different etiologies may give rise to multiple subtypes of CAD that could benefit from alternative preventions and treatments. However, so far, there have been no systematic efforts to predict CAD subtypes using clinical and genetic factors.

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  • Transradial arterial access offers advantages over femoral access in coronary interventions, including reduced bleeding, improved patient comfort, and shorter hospital stays, leading to increasing interest in its use for peripheral vascular procedures.
  • Despite its benefits, challenges remain, and ongoing development of specialized equipment is necessary for effective use in these interventions.
  • Current studies suggest that transradial access is generally safe and associated with fewer complications, but further large-scale randomized trials are needed to fully understand its impact on patient outcomes and to identify suitable patient selection criteria.
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Sudden cardiac arrest (SCA) represents a major cause of premature mortality globally, with enormous impact and financial cost to victims, families, and communities. SCA prevention should be considered a health priority in Australia. National Cardiac Arrest Summits were held in June 2022 and March 2023, with inclusion from multi-faceted endeavours related to SCA prevention.

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  • Fibromuscular dysplasia (FMD) is a rare condition mostly affecting women, characterized by various arterial problems that can lead to serious health issues like hypertension and stroke.* -
  • This study used genetic data from FMD patients and healthy controls to identify 18 gene regulatory networks, with four forming an FMD-related supernetwork affecting arterial health.* -
  • By disrupting this supernetwork in mice, researchers observed symptoms of FMD, revealing insights into the disease's mechanisms and potential new treatment options.*
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Aims: Vein grafts are used for many indications, including bypass graft surgery and arteriovenous fistula (AVF) formation. However, patency following vein grafting or AVF formation is suboptimal for various reasons, including thrombosis, neointimal hyperplasia, and adverse remodelling. Recently, endothelial-to-mesenchymal transition (EndMT) was found to contribute to neointimal hyperplasia in mouse vein grafts.

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  • - Hypermobile Ehlers-Danlos syndrome (hEDS) is a common inherited connective tissue disorder, but its genetic causes are still unknown.
  • - Researchers conducted whole exome sequencing on families and sporadic patients with hEDS, discovering a specific missense variant in the KLK15 gene linked to the disease.
  • - By creating knock-in mice with this variant, they validated that it caused connective tissue defects, supporting the role of KLK15 gene variants in hEDS and promoting early diagnosis and improved clinical treatments.
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Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression.

Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL.

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Various forms of pollution carry a substantial burden with respect to increasing the risk of causing and exacerbating noncommunicable diseases, especially cardiovascular disease. The first part of this 2-part series on pollution and cardiovascular disease provided an overview of the impact of global warming and air pollution. This second paper provides an overview of the impact of water, soil, noise, and light pollution on the cardiovascular system.

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Environmental stresses are increasingly recognized as significant risk factors for adverse health outcomes. In particular, various forms of pollution and climate change are playing a growing role in promoting noncommunicable diseases, especially cardiovascular disease. Given recent trends, global warming and air pollution are now associated with substantial cardiovascular morbidity and mortality.

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Tricuspid valve disease is an often underrecognized clinical problem that is associated with significant morbidity and mortality. Unfortunately, patients will often present late in their disease course with severe right-sided heart failure, pulmonary hypertension, and life-limiting symptoms that have few durable treatment options. Traditionally, the only treatment for tricuspid valve disease has been medical therapy or surgery; however, there have been increasing interest and success with the use of transcatheter tricuspid valve therapies over the past several years to treat patients with previously limited therapeutic options.

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Article Synopsis
  • The study investigates the gene expression changes in vascular cells during atherosclerosis progression, emphasizing the limited understanding of their clinical significance.
  • It utilizes single-cell RNA sequencing data from both mouse models and human tissue to identify various cell subtypes involved in advanced atherosclerosis and symptomatic carotid plaques.
  • The findings highlight the association of specific gene-regulatory networks with coronary artery disease severity, suggesting pathways that may be targeted for therapeutic strategies.
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Endothelial cells (ECs) line the luminal surface of blood vessels and play a major role in vascular (patho)-physiology by acting as a barrier, sensing circulating factors and intrinsic/extrinsic signals. ECs have the capacity to undergo endothelial-to-mesenchymal transition (EndMT), a complex differentiation process with key roles both during embryonic development and in adulthood. EndMT can contribute to EC activation and dysfunctional alterations associated with maladaptive tissue responses in human disease.

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