Outcomes of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia Treated With β-Blockers

Mazzanti, Andrea; Kukavica, Deni; Trancuccio, Alessandro; Memmi, Mirella; Bloise, Raffaella; Gambelli, Patrick; Marino, Maira; Ortíz-Genga, Martín; Morini, Massimo; Monteforte, Nicola; Giordano, Umberto; Keegan, Roberto; Tomasi, Luca; Anastasakis, A; Davis, Andrew M.; Shimizu, Wataru; Blom, Nico A.; Santiago, Demetrio J.; Carlo, Napolitano; Monserrat, Lorenzo; Priori, Silvia G.

doi:10.1001/jamacardio.2022.0219

Cited by 37 publications

(37 citation statements)

References 30 publications

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“…According to European Society of Cardiology guidelines [ 51 ], the first-line therapy for CPVT is beta-blockers to suppress the catecholamine stimulation of the β-adrenergic pathway. It was very recently reported that non-selective β-blockers (nadolol, propranolol) were more efficient at reducing the risk of life-threatening arrhythmic events compared with selective β-blockers [ 52 ]. If beta-blocker therapy is ineffective, additional treatment with flecainide is recommended.…”

Section: Cardiac Disease Associated With Ryr2 Mutationsmentioning

confidence: 99%

Molecular, Subcellular, and Arrhythmogenic Mechanisms in Genetic RyR2 Disease

Fowler

Zissimopoulos

2022

Biomolecules

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The ryanodine receptor (RyR2) has a critical role in controlling Ca2+ release from the sarcoplasmic reticulum (SR) throughout the cardiac cycle. RyR2 protein has multiple functional domains with specific roles, and four of these RyR2 protomers are required to form the quaternary structure that comprises the functional channel. Numerous mutations in the gene encoding RyR2 protein have been identified and many are linked to a wide spectrum of arrhythmic heart disease. Gain of function mutations (GoF) result in a hyperactive channel that causes excessive spontaneous SR Ca2+ release. This is the predominant cause of the inherited syndrome catecholaminergic polymorphic ventricular tachycardia (CPVT). Recently, rare hypoactive loss of function (LoF) mutations have been identified that produce atypical effects on cardiac Ca2+ handling that has been termed calcium release deficiency syndrome (CRDS). Aberrant Ca2+ release resulting from both GoF and LoF mutations can result in arrhythmias through the Na+/Ca2+ exchange mechanism. This mini-review discusses recent findings regarding the role of RyR2 domains and endogenous regulators that influence RyR2 gating normally and with GoF/LoF mutations. The arrhythmogenic consequences of GoF/LoF mutations will then be discussed at the macromolecular and cellular level.

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Section: Cardiac Disease Associated With Ryr2 Mutationsmentioning

confidence: 99%

Molecular, Subcellular, and Arrhythmogenic Mechanisms in Genetic RyR2 Disease

Fowler

Zissimopoulos

2022

Biomolecules

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“…In this cohort, the de novo cases presented with an arrhythmic event (syncope or cardiac arrest) at a younger age. 41 Lifestyle changes and supportive care are crucial for all patients with CPVT. Furthermore, all patients with CPVT should be treated with pharmacological therapies to reduce the incidence of the primary manifestations of the disease.…”

Section: Risk Stratification and Treatmentmentioning

confidence: 99%

“…Notably, data on long-term arrhythmic events in CPVT patients on dual therapy (β-blocker and flecainide) with or without LCSD are still lacking. 41 Based on the data available and in the absence of randomised trials, it seems reasonable to recommend a conservative approach towards using ICDs in patients with CPVT in line with the current guidelines. Indeed, when an ICD is implanted following a shared decision-making process, the treating physician should seek to minimise the risk of appropriate and inappropriate therapy by optimising medical treatment with or without LCSD.…”

Section: Pharmacological Therapymentioning

confidence: 99%

Catecholaminergic Polymorphic Ventricular Tachycardia

Abbas

Miles

Behr

2022

Arrhythm Electrophysiol Rev

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Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterised by adenergically mediated bidirectional and/or polymorphic ventricular tachycardia. CPVT is a significant cause of autopsy-negative sudden death in children and adolescents, although it can also affect adults. It is often caused by pathogenic variants in the cardiac ryanodine receptor gene as well as other rarer genes. Early identification and risk stratification is of major importance. β-blockers are the cornerstone of therapy. Sodium channel blockers, specifically flecainide, have an additive role. Left cardiac sympathetic denervation is playing an increasing role in suppression of arrhythmia and symptoms. Concerns have been raised, however, about the efficacy of implantable cardioverter defibrillator therapy and the risk of catecholamine driven proarrhythmic storms. In this review, we summarise the clinical characteristics, genetics, and diagnostic and therapeutic strategies for CPVT and describe recent advances and challenges.

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“…Amongst patients who survived an attempt of SCD, or present with syncope/sustained VT/VF despite maximal medical therapy, current evidence recommends the use of an implantable cardioverter-defibrillator (ICD) for primary/secondary SCD prevention [ 18 , 19 , 20 ]. However, although ICD implantation is associated with reduced mortality amongst high risk CPVT patients, it should be noted that ICD shocks come with a risk of triggering ventricular tachyarrhythmia under a vicious cycle of adrenergic stimulation, thus potentially increasing the morbidity and mortality amongst this cohort of patients [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical Characteristics, Genetic Findings and Arrhythmic Outcomes of Patients with Catecholaminergic Polymorphic Ventricular Tachycardia from China: A Systematic Review

Leung¹,

Lee²,

Zhou

et al. 2022

Life

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Introduction: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited cardiac ion channelopathy. The present study aims to examine the clinical characteristics, genetic basis, and arrhythmic outcomes of CPVT patients from China to elucidate the difference between CPVT patients in Asia and Western countries. Methods: PubMed and Embase were systematically searched for case reports or series reporting on CPVT patients from China until 19 February 2022 using the keyword: “Catecholaminergic Polymorphic Ventricular Tachycardia” or “CPVT”, with the location limited to: “China” or “Hong Kong” or “Macau” in Embase, with no language or publication-type restriction. Articles that did not state a definite diagnosis of CPVT and articles with duplicate cases found in larger cohorts were excluded. All the included publications in this review were critically appraised based on the Joanna Briggs Institute Critical Appraisal Checklist. Clinical characteristics, genetic findings, and the primary outcome of spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF) were analyzed. Results: A total of 58 unique cases from 15 studies (median presentation age: 8 (5.0–11.8) years old) were included. All patients, except one, presented at or before 19 years of age. There were 56 patients (96.6%) who were initially symptomatic. Premature ventricular complexes (PVCs) were present in 44 out of 51 patients (86.3%) and VT in 52 out of 58 patients (89.7%). Genetic tests were performed on 54 patients (93.1%) with a yield of 87%. RyR2, CASQ2, TERCL, and SCN10A mutations were found in 35 (71.4%), 12 (24.5%), 1 (0.02%) patient, and 1 patient (0.02%), respectively. There were 54 patients who were treated with beta-blockers, 8 received flecainide, 5 received amiodarone, 2 received verapamil and 2 received propafenone. Sympathectomy (n = 10), implantable cardioverter-defibrillator implantation (n = 8) and ablation (n = 1) were performed. On follow-up, 13 patients developed VT/VF. Conclusion: This was the first systematic review of CPVT patients from China. Most patients had symptoms on initial presentation, with syncope as the presenting complaint. RyR2 mutation accounts for more than half of the CPVT cases, followed by CASQ2, TERCL and SCN10A mutations.

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Outcomes of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia Treated With β-Blockers

Cited by 37 publications

References 30 publications

Molecular, Subcellular, and Arrhythmogenic Mechanisms in Genetic RyR2 Disease

Molecular, Subcellular, and Arrhythmogenic Mechanisms in Genetic RyR2 Disease

Catecholaminergic Polymorphic Ventricular Tachycardia

Clinical Characteristics, Genetic Findings and Arrhythmic Outcomes of Patients with Catecholaminergic Polymorphic Ventricular Tachycardia from China: A Systematic Review

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