Publications by authors named "Jason C Kovacic"

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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  • 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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  • 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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  • - 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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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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  • 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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Randomized controlled trials of continuous positive airway pressure (CPAP) therapy for cardiovascular disease (CVD) prevention among patients with obstructive sleep apnea (OSA) have been largely neutral. However, given that OSA is a heterogeneous disease, there may be unidentified subgroups demonstrating differential treatment effects. We sought to apply a novel data-drive approach to identify nonsleepy OSA subgroups with heterogeneous effects of CPAP on CVD outcomes within the Impact of Sleep Apnea Syndrome in the Evolution of Acute Coronary Syndrome (ISAACC) study.

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Background: Imaging with late gadolinium enhancement (LGE) magnetic resonance (MR) and F-fluorodeoxyglucose (F-FDG) PET allows complementary assessment of myocardial injury and disease activity and has shown promise for improved characterization of active cardiac sarcoidosis (CS) based on the combined positive imaging outcome, MR(+)PET(+).

Objectives: This study aims to evaluate qualitative and quantitative assessments of hybrid MR/PET imaging in CS and to evaluate its association with cardiac-related outcomes.

Methods: A total of 148 patients with suspected CS underwent hybrid MR/PET imaging.

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Importance: Spontaneous coronary artery dissection (SCAD) is a poorly understood cause of acute coronary syndrome that predominantly affects women. Evidence to date suggests a complex genetic architecture, while a family history is reported for a minority of cases.

Objective: To determine the contribution of rare and common genetic variants to SCAD risk in familial cases, the latter via the comparison of a polygenic risk score (PRS) with those with sporadic SCAD and healthy controls.

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Genome-wide association studies (GWASs) have identified hundreds of risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in GWASs, and the causal gene-regulatory mechanisms of these risk loci during atherosclerosis remain unclear. We incorporated local ancestry and haplotypes to identify quantitative trait loci for expression (eQTLs) and splicing (sQTLs) in coronary arteries from 138 ancestrally diverse Americans.

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As disease-specific interventions for dementia are being developed, the ability to identify the underlying pathology and dementia subtypes is increasingly important. Vascular cognitive impairment and dementia (VCID) is the second most common cause of dementia after Alzheimer disease, but progress in identifying molecular biomarkers for accurate diagnosis of VCID has been relatively limited. In this Review, we examine the roles of large and small vessel disease in VCID, considering the underlying pathophysiological processes that lead to vascular brain injury, including atherosclerosis, arteriolosclerosis, ischaemic injury, haemorrhage, hypoperfusion, endothelial dysfunction, blood-brain barrier breakdown, inflammation, oxidative stress, hypoxia, and neuronal and glial degeneration.

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  • Coronary artery disease (CAD) involves the buildup of atherosclerotic plaques in arteries, with complex interactions between vascular and immune cells contributing to its progression.
  • This study integrates data from 22 single-cell RNA sequencing libraries, analyzing 118,578 cells to map human atherosclerosis and to better understand cell diversity and communication.
  • Key findings include the identification of smooth muscle cell (SMC) markers linked to CAD and atherosclerosis progression, which were validated through various analyses, aiming to inform future cardiovascular research.
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Senescent cells are a major contributor to age-dependent cardiovascular tissue dysfunction, but knowledge of their in vivo cell markers and tissue context is lacking. To reveal tissue-relevant senescence biology, we integrate the transcriptomes of 10 experimental senescence cell models with a 224 multi-tissue gene co-expression network based on RNA-seq data of seven tissues biopsies from ∼600 coronary artery disease (CAD) patients. We identify 56 senescence-associated modules, many enriched in CAD GWAS genes and correlated with cardiometabolic traits-which supports universality of senescence gene programs across tissues and in CAD.

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