Ventricular pre‐excitation and cardiac hypertrophy mimicking hypertrophic cardiomyopathy in a Turkish family with a novel PRKAG2 mutation

Bayrak, Fatih; Kömürcü-Bayrak, Evrim; Mutlu, Bülent; Kahveci, Gökhan; Başaran, Yelda; Erginel-Unaltuna, Nihan

doi:10.1016/j.ejheart.2006.03.006

Cited by 32 publications

(21 citation statements)

References 17 publications

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“…5, 7, 8, 11, 12, 17 Maximal ventricular wall thickness varied widely among the studies, ranging from normal values to a mean of 24 mm (confidence interval 13 – 45 mm) among Asn488Ile patients 7 and 32.8±7.9 mm in Glu506Lys patients. 12 Restrictive mitral inflow Doppler pattern, 7 hemodynamically significant left ventricular outflow tract obstruction, 12 and dilated progression were leading causes to cardiac transplant or SCD. 8 In all studies ultrasound imaging was routinely used to assess cardiac hypertrophy; only a minority of patients underwent cardiovascular magnetic resonance (CMR) for tissue characterization (Figure 2 panel B-C).…”

Section: Resultsmentioning

confidence: 99%

Clinical Spectrum of PRKAG2 Syndrome

Porto

Brun

Severini

et al. 2016

Circ: Arrhythmia and Electrophysiology

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Section: Resultsmentioning

confidence: 99%

Clinical Spectrum of PRKAG2 Syndrome

Porto

Brun

Severini

et al. 2016

Circ: Arrhythmia and Electrophysiology

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“…AMP-activated protein kinase (AMPK), which has a key role in the control and regulation of energy metabolism, stimulates fatty acid metabolism and glycolysis, preserving ATP production71, 72. AMPK activation in ventricular hypertrophy73-75 preserves ATP levels by increasing glucose transport and accelerating glycolysis and by inhibiting acetyl CoA carboxylase72. In RVH, there is systolic flow impediment in the right coronary artery that is proportional to RV pressure and mass76.…”

Section: The Right Ventricle (Rv) In Pahmentioning

confidence: 99%

Basic Science of Pulmonary Arterial Hypertension for Clinicians

Weir²,

2010

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P ulmonary arterial hypertension (PAH) is a syndrome in which pulmonary arterial obstruction increases pulmonary vascular resistance, which leads to right ventricular (RV) failure and a 15% annual mortality rate. The present review highlights recent advances in the basic science of PAH. New concepts clarify the nature of PAH and provide molecular blueprints that explain how PAH is initiated and maintained. Five basic science concepts provide a framework to understand and treat PAH: (1) Endothelial dysfunction creates an imbalance that favors vasoconstriction, thrombosis, and mitogenesis. Restoration of this balance by inhibition of endothelin and thromboxane or augmentation of nitric oxide (NO) and prostacyclin is the paradigm on which most current therapy is based. (2) PAH has a genetic component. Mutations (bone morphogenetic protein receptor-2 [BMPR2]) and single-nucleotide polymorphisms (SNPs; ion channels and transporter genes) predispose to PAH. (3) Excess proliferation, impaired apoptosis, and glycolytic metabolism in pulmonary artery smooth muscle, fibroblasts, and endothelial cells suggest analogies to cancer. Many experimental therapies reduce PAH by decreasing the proliferation/apoptosis ratio; these include inhibitors of pyruvate dehydrogenase kinase (PDK), serotonin transporters (SERT), survivin, 3-hydroxy-3-methylglutaryl coenzyme A reductase, transcription factors (hypoxia-inducible factor [HIF]-1␣ and nuclear factor of activated T lymphocytes [NFAT]), and tyrosine kinases. Augmentation of voltage-gated K ϩ channels (Kv1.5) and BMPR2 signaling also addresses this imbalance. Tyrosine kinase inhibitors used to treat cancer are currently in phase 1 PAH trials. (4) Refractory vasoconstriction may occur due to rho kinase activation. Fewer than 20% of PAH patients respond to conventional vasodilators; however, refractory vasoconstriction may respond to rho kinase inhibitors. (5) The RV can be targeted therapeutically. Although increased afterload initiates RV failure, which is the major cause of death/dysfunction in PAH, the RV may be amenable to cardiac-targeted therapies. The RV in PAH has features of ischemic, hibernating myocardium.Guided by these new concepts and armed with a better understanding of disease mechanisms, we are poised to identify new therapeutic targets. To achieve balance in a rapidly evolving field, we invited colleagues to contribute Figures and legends illustrating pathways in their area of expertise that are important to the pathogenesis and treatment of PAH. These contributors are acknowledged in the Acknowledgments section.

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“…Associated right ventricular hypertrophy may also be found. 85 The principal electrophysiological abnormalities in young individuals is ventricular preexcitation, found in approximately two-thirds of genetically affected individuals, is often associated with supraventricular arrhythmias (atrial fibrillation and, less commonly, atrioventricular reentry tachycardia). Conduction-system abnormalities develop in Ϸ50% of older mutation carriers, often necessitating pacemaker implantation.…”

Section: Mutations In the Humanmentioning

confidence: 99%

AMP-Activated Protein Kinase in the Heart

Arad

Seidman

2007

Circulation Research

305

291

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Abstract-AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that is expressed in most mammalian tissues including cardiac muscle. Among the multiple biological processes influenced by AMPK, regulation of fuel supply and energy-generating pathways in response to the metabolic needs of the organism is fundamental and likely accounts for the remarkable evolutionary conservation of this enzyme complex. By regulating the activity of acetyl-coenzyme A carboxylase, AMPK affects levels of malonyl-coenzyme A, a key energy regulator in the cell. AMPK is generally quiescent under normal conditions but is activated in response to hormonal signals and stresses sufficient to produce an increase in AMP/ATP ratio, such as hypoglycemia, strenuous exercise, anoxia, and ischemia. Once active, muscle AMPK enhances uptake and oxidative metabolism of fatty acids as well as increases glucose transport and glycolysis. Data from AMPK deficiency models suggest that AMPK activity might influence the pathophysiology and therapy of diabetes and increase heart tolerance to ischemia. Effects that are not as well understood include AMPK regulation of transcription. Different AMPK isoforms are found in distinct locations within the cell and have distinct functions in different tissues. A principal mode of AMPK activation is phosphorylation by upstream kinases (eg, LKB1). These kinases have a fundamental role in cell-cycle regulation and protein synthesis, suggesting involvement in a number of human disorders including cardiac hypertrophy, apoptosis, cancer, and atherosclerosis. The physiological role played by AMPK during health and disease is far from being clearly defined. Naturally occurring mutations affecting the nucleotide-sensing modules in the regulatory ␥ subunit of AMPK lead to enzyme dysregulation and inappropriate activation under resting conditions. Glycogen accumulation ensues, leading to human disease manifesting as cardiac hypertrophy, accessory atrioventricular connections, and degeneration of the physiological conduction system. Whether AMPK is a key participant or bystander in other disease states and whether its selective manipulation may significantly benefit these conditions remain important questions. (Circ Res. 2007;100:474-488.)

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Ventricular pre‐excitation and cardiac hypertrophy mimicking hypertrophic cardiomyopathy in a Turkish family with a novel PRKAG2 mutation

Cited by 32 publications

References 17 publications

Clinical Spectrum of PRKAG2 Syndrome

Clinical Spectrum of PRKAG2 Syndrome

Basic Science of Pulmonary Arterial Hypertension for Clinicians

AMP-Activated Protein Kinase in the Heart

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