Evidence of Clonal Hematopoiesis and Risk of Heart Failure
- PDF / 253,778 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 51 Downloads / 181 Views
BIOMARKERS OF HEART FAILURE (WH TANG & J GRODIN, SECTION EDITORS)
Evidence of Clonal Hematopoiesis and Risk of Heart Failure Peter Bazeley 1 & Rommel Morales 2 & W. H. Wilson Tang 2,3
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by persistent clonal expansion of adult hematopoietic stem cells, which has been increasingly found to be associated with cardiovascular disease and adverse outcomes in heart failure. Here we outline emerging studies on the prevalence of CHIP, and its association with cardiovascular and heart disease. Recent Findings Previous genomic studies have found CHIP mutations to be associated with increased risks of arterial disease, stroke, and mortality. Murine studies exploring TET2, DNMT3A, and JAK2 mutations have shown changes in cellularity that decrease cardiac function after insult, as well as increase inflammasome activation. Summary Mutations in driver genes are associated with worse clinical outcomes in heart failure patients, as a potential result of the proinflammatory selection in clonal hematopoiesis. Advances in the field have yielded therapeutic targets tested in recent clinical studies and may provide a valuable diagnostic of risk in heart failure. Keywords CHIP . Clonal hematopoiesis . Heart failure . Ten-eleven translocation-2 . Janus kinase 2 . Inflammasome
Introduction
Germline Variation
Heart failure (HF) is a significant medical burden, comprising the leading cause of hospitalization in patients over 65 and exceeding $31B annually in care expenditures [1]. Thus, early diagnostic and prognostic tools are becoming increasingly emphasized in the clinical arena. Traditional risk factor assessments include HF risk scores, imaging modalities such as echocardiography and cardiac MRI, and electronic health record-based algorithmic approaches [2–7]. However, while these approaches are effective at risk assessment, additional strategies such as genomic measures may provide a complementary resource to other clinical modalities.
It is known that HF involves a complex interplay of environmental and genetic factors affecting risk, progression, and therapeutic response [8]. Much work identifying genetic HF risk has focused on germline variation, such as found in familial cardiomyopathies [9]. Familial cardiomyopathy accounts for 50% of total dilated cardiomyopathy cases, with 40% of these having known genetic causes [10]. Additionally, hypertrophic cardiomyopathy often presents as a monogenic disorder, associated with single mutations in up to 18 genes [11]. Therefore, genetic testing is recommended for patients with family members presenting with dilated, hypertrophic, and restrictive cardiomyopathies [12]. To date, nearly 300 HF-associated variants have been identified, with a meta-analysis of more than 73,000 subjects revealing 52 loci of interest, correlating to QRS phenotypes and myocardial hypertrophy [13, 14]. Recently, a genome-wide association study (GWA
Data Loading...
