Barth Syndrome-Related Cardiomyopathy is Associated with a Reduction in Myocardial Glucose Oxidation

Am J Physiol Heart Circ Physiol. 2021 Apr 30. doi: 10.1152/ajpheart.00873.2020. Online ahead of print.ABSTRACTHeart failure presents as the leading cause of infant mortality in individuals with Barth syndrome (BTHS), a rare genetic disorder due to mutations in the tafazzin (TAZ) gene affecting mitochondrial structure and function. Investigations into the perturbed bioenergetics in the BTHS heart remain limited. Hence, our objective was to identify the potential alterations in myocardial energy metabolism and molecular underpinnings that may contribute to the early cardiomyopathy and heart failure development in BTHS. Cardiac function and myocardial energy metabolism were assessed via ultrasound echocardiography and isolated working heart perfusions, respectively, in a mouse model of BTHS (doxycycline-inducible Taz knockdown (TazKD) mice). In addition, we also performed mRNA/protein expression profiling for key regulators of energy metabolism in hearts from TazKD mice and their wild-type (WT) littermates. TazKD mice developed hypertrophic cardiomyopathy as evidenced by increased left ventricular anterior and posterior wall thickness, as well as increased cardiac myocyte cross sectional area, though no functional impairments were observed. Glucose oxidation rates were markedly reduced in isolated working hearts from TazKD mice compared to their WT littermates in the presence of insulin, which was associated with decreased pyruvate dehydrogenase activity. Conversely, myocardial ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Source Type: research

Related Links:

Hypertrophic cardiomyopathy (HCM) is a very intriguing heritable disease, definied as left ventricular hypertrophy in the absence of a secondary cause. The heterogenity in phenotypic expression makes treatment of patients very challenging. Fortunately, most patients have a benign prognosis, however in a subset of patients the clinical outcome is less favourable as patients present with symptoms of congestive heart failure or sudden cardiac death [1]. Symptoms are often related to left ventricular outflow tract (LVOT) obstruction.
Source: International Journal of Cardiology - Category: Cardiology Authors: Tags: Editorial Source Type: research
Conclusions: Our study found that HCM-associated TNNT2 variants increased cardiac microtissue contraction, while DCM-associated variants cause decreased contraction, both of which paralleled changes in myofilament calcium affinity. Transcriptomic changes, including NPPB levels, directly correlated with sarcomere function and can be utilized to predict TNNT2 variant pathogenicity. PMID: 33025817 [PubMed - as supplied by publisher]
Source: Circulation - Category: Cardiology Authors: Tags: Circulation Source Type: research
AbstractThe epidemiologic data for pediatric hypertrophic cardiomyopathy (HCM)  needs to be periodically updated as diagnostic techniques and management strategies improve. Herein, the incidence, prevalence, and mortality rates of pediatric HCM in a population-based treatment system are described. Patients aged ≤ 17 years and diagnosed with HCM on service visits over a 10-year period in one state Medicaid database (2007–2016) were analyzed. The cohort included 137 unique patients; 64.2% were male; 40.9% were African American; 42.3% were first diagnosed ≤ 24 months...
Source: Mammalian Genome - Category: Genetics & Stem Cells Source Type: research
AbstractAimsAmyloid cardiomyopathy is an underappreciated cause of morbidity and mortality. Recent evidence suggests that ATTR wild ‐type cardiomyopathy (ATTRwt‐CM) is probably much more common than widely appreciated. So far, no data are available on comparison of mortality from ATTRwt‐CM and other heart failure aetiologies.Methods and resultsThis was a retrospective, observational, cohort study of 2251 patients and their data collected prospectively from May 2000 to June 2018. Long ‐term mortality was the main outcome measure. Underlying cardiomyopathies were classified as amyloid CM (6.1%) [ATTRwt 3.0%; light‐...
Source: ESC Heart Failure - Category: Cardiology Authors: Tags: Original Research Article Source Type: research
AbstractBarth syndrome (BTHS) is a rare, X-linked recessive, infantile-onset debilitating disorder characterized by early-onset cardiomyopathy, skeletal muscle myopathy, growth delay, and neutropenia, with a worldwide incidence of 1/300,000 –400,000 live births. The high mortality rate throughout infancy in BTHS patients is related primarily to progressive cardiomyopathy and a weakened immune system. BTHS is caused by defects in the TAZ gene that encodes tafazzin, a transacylase responsible for the remodeling and maturation of the mi tochondrial phospholipid cardiolipin (CL), which is critical to normal mitochondrial...
Source: Heart Failure Reviews - Category: Cardiology Source Type: research
Hypertrophic cardiomyopathy (HCM) is the most common inherited disease, with a prevalence of 1:200 worldwide. The cause of HCM usually presents with an autosomal dominant mutation in the genes encoding one of more than 20 sarcomeric proteins, incomplete penetrance, and variable expressivity. HCM classically manifests as an unexplained thickness of the interventricular septum (IVS) and left ventricular (LV) walls, with or without the obstruction of the LV outflow tract (LVOT), and variable cardiac arrhythmias. Here, we present a rare case of mixed cardiomyopathy (cardiac hypertrophy and dilation) and erythrocytosis in a you...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
AbstractAimsCardiomyopathies are a heterogeneous group of disorders that increase the risk for atrial fibrillation (AF). The aim of the study is to assess the prevalence of AF, anticoagulation management, and risk of stroke/transient ischaemic attack (TIA) in patients with cardiomyopathy.Methods and resultsThree thousand two hundred eight consecutive adult patients with cardiomyopathy (34.9% female; median age: 55.0  years) were prospectively enrolled as part of the EURObservational Research Programme Cardiomyopathy/Myocarditis Registry. At baseline, 903 (28.2%) patients had AF (29.4% dilated, 27.5% hypertrophic, 51.5...
Source: ESC Heart Failure - Category: Cardiology Authors: Tags: Original Research Article Source Type: research
Atrial fibrillation (AF) in hypertrophic cardiomyopathy (HC) is associated with significant symptomatic deterioration, heart failure and thromboembolic disease. There is a need for better mechanistic insight and improved identification of at risk patients. We used CMR to assess predictors of AF in HC, in particular the role of myocardial fibrosis. Consecutive patients with HC referred for CMR 2003-2013 were prospectively enrolled. CMR parameters including left ventricular volumes, presence and percentage of late gadolinium enhancement in the left ventricle (%LGE) and left atrial volume index (LAVi) were measured.
Source: The American Journal of Cardiology - Category: Cardiology Authors: Source Type: research
AbstractTraditionally thought of primarily as the predominant regulator of myocardial perfusion, it is becoming more accepted that the human coronary microvasculature also exerts a more direct influence on the surrounding myocardium. Coronary microvascular dysfunction (CMD), not only precedes large artery atherosclerosis, but is associated with other cardiovascular diseases such as heart failure with preserved ejection fraction (HFpEF) and hypertrophic cardiomyopathy (HCM). It is also highly predictive of cardiovascular events in patients with or without atherosclerotic cardiovascular disease. This review focuses on this r...
Source: Microcirculation - Category: Research Authors: Tags: INVITED REVIEWS Source Type: research
As the most metabolically demanding organ in the body, the heart must generate massive amounts of energy adenosine triphosphate (ATP) from the oxidation of fatty acids, carbohydrates and other fuels (e.g., amino acids, ketone bodies), in order to sustain constant contractile function. While the healthy mature heart acts omnivorously and is highly flexible in its ability to utilize the numerous fuel sources delivered to it through its coronary circulation, the heart’s ability to produce ATP from these fuel sources becomes perturbed in numerous cardiovascular disorders. This includes ischemic heart disease and myocardi...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
More News: Cardiology | Cardiomyopathy | Doxycycline | Genetics | Heart | Heart Failure | Hypertrophic Cardiomyopathy | Insulin | Physiology | Ultrasound