Catecholaminergic Polymorphic Ventricular Tachycardia

Liu, Nian; Napolitano, Carlo; Priori, Silvia G.

doi:10.1007/978-1-4471-4881-4_31

Cited by 8 publications

(15 citation statements)

References 41 publications

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“…CPVT has a poor prognosis, particularly in males with a RyR2 mutation. It likely contributes ϳ15% of SCD in structurally normal hearts (678,1123). A third of CPVT patients have family histories of premature sudden death or stress-related syncope (625).…”

Section: Clinical Features Of Cpvtmentioning

confidence: 99%

“…This would particularly affect Purkinje fibers owing to their greater susceptibility than ventricular myocytes to Ca 2ϩ overload due to their greater Na ϩ loads and longer APDs (1174). Clinical arrhythmic activity in both CPVT and digitalis toxicity is thus accompanied by bidirectional VT reflected in alternating 180°rotations of the electrocardiographic QRS axis between beats (625,674). This can then be followed by degeneration into rapid polymorphic VT and VF.…”

Section: Electrocardiographic Features Of Murine Models With Genetically Modified Ryr2mentioning

confidence: 99%

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Murine Electrophysiological Models of Cardiac Arrhythmogenesis

Huang

2017

Physiological Reviews

197

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Cardiac arrhythmias can follow disruption of the normal cellular electrophysiological processes underlying excitable activity and their tissue propagation as coherent wavefronts from the primary sinoatrial node pacemaker, through the atria, conducting structures and ventricular myocardium. These physiological events are driven by interacting, voltage-dependent, processes of activation, inactivation, and recovery in the ion channels present in cardiomyocyte membranes. Generation and conduction of these events are further modulated by intracellular Ca homeostasis, and metabolic and structural change. This review describes experimental studies on murine models for known clinical arrhythmic conditions in which these mechanisms were modified by genetic, physiological, or pharmacological manipulation. These exemplars yielded molecular, physiological, and structural phenotypes often directly translatable to their corresponding clinical conditions, which could be investigated at the molecular, cellular, tissue, organ, and whole animal levels. Arrhythmogenesis could be explored during normal pacing activity, regular stimulation, following imposed extra-stimuli, or during progressively incremented steady pacing frequencies. Arrhythmic substrate was identified with temporal and spatial functional heterogeneities predisposing to reentrant excitation phenomena. These could arise from abnormalities in cardiac pacing function, tissue electrical connectivity, and cellular excitation and recovery. Triggering events during or following recovery from action potential excitation could thereby lead to sustained arrhythmia. These surface membrane processes were modified by alterations in cellular Ca homeostasis and energetics, as well as cellular and tissue structural change. Study of murine systems thus offers major insights into both our understanding of normal cardiac activity and its propagation, and their relationship to mechanisms generating clinical arrhythmias.

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Section: Clinical Features Of Cpvtmentioning

confidence: 99%

Section: Electrocardiographic Features Of Murine Models With Genetically Modified Ryr2mentioning

confidence: 99%

Murine Electrophysiological Models of Cardiac Arrhythmogenesis

Huang

2017

Physiological Reviews

197

View full text Add to dashboard Cite

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“…It can present as sudden death in children without any prior signs or warning, 6 and it has been estimated to cause up to 15% of unexplained sudden cardiac deaths in young people. 7 Previously, familial assessment revealed little evidence of the condition in many victims of unexplained sudden death. 8,9 Mutations in the ryanodine receptor 2 gene (RYR2 [MIM 180902]) are known to cause dominantly inherited CPVT 10 ), respectively, have in addition been found in a low number of individuals diagnosed with CPVT.…”

mentioning

confidence: 99%

Mutations in Calmodulin Cause Ventricular Tachycardia and Sudden Cardiac Death

Nyegaard

Overgaard

Søndergaard

et al. 2012

The American Journal of Human Genetics

358

339

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Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion in individuals without structural cardiac abnormalities. Although rare, CPVT is suspected to cause a substantial part of sudden cardiac deaths in young individuals. Mutations in RYR2, encoding the cardiac sarcoplasmic calcium channel, have been identified as causative in approximately half of all dominantly inherited CPVT cases. Applying a genome-wide linkage analysis in a large Swedish family with a severe dominantly inherited form of CPVT-like arrhythmias, we mapped the disease locus to chromosome 14q31-32. Sequencing CALM1 encoding calmodulin revealed a heterozygous missense mutation (c.161A>T [p.Asn53Ile]) segregating with the disease. A second, de novo, missense mutation (c.293A>G [p.Asn97Ser]) was subsequently identified in an individual of Iraqi origin; this individual was diagnosed with CPVT from a screening of 61 arrhythmia samples with no identified RYR2 mutations. Both CALM1 substitutions demonstrated compromised calcium binding, and p.Asn97Ser displayed an aberrant interaction with the RYR2 calmodulin-binding-domain peptide at low calcium concentrations. We conclude that calmodulin mutations can cause severe cardiac arrhythmia and that the calmodulin genes are candidates for genetic screening of individual cases and families with idiopathic ventricular tachycardia and unexplained sudden cardiac death.

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“…Catecholaminergic polymorphic ventricular tachycardia is an exercise-or emotional-induced polymorphic ventricular tachycardia that occurs in the absence of structural abnormalities. 332,333 Many incidences of CPVT are caused by mutations to the RyR2 or CASQ2 genes, which encode proteins that are responsible for Ca 2+ handling and transport. Using engineered heart tissue on a thin film cantilever array and Ca 2+ imaging, Park et al demonstrated hallmarks of CPVT with patient-derived iPSC-CMs, including re-entrant arrhythmia after electrical pacing and catecholamine (isoproterenol) administration.…”

Section: Myocardial Infarction and Ischemia-reperfusion Injurymentioning

confidence: 99%