No CrossRef data available.
Article contents
Clinical and genetic characteristics of catecholaminergic polymorphic ventricular tachycardia combined with left ventricular non-compaction
Published online by Cambridge University Press: 29 November 2023
Abstract
Background:
Catecholaminergic polymorphic ventricular tachycardia is an ion channelopathy, caused by mutations in genes coding for calcium-handling proteins. It can coexist with left ventricular non-compaction. We aim to investigate the clinical and genetic characteristics of this co-phenotype.
Methods:
Medical records of 24 patients diagnosed with catecholaminergic polymorphic ventricular tachycardia in two Chinese hospitals between September, 2005, and January, 2020, were retrospectively reviewed. We evaluated their clinical and genetic characteristics, including basic demographic data, electrocardiogram parameters, medications and survival during follow-up, and their gene mutations. We did structural analysis for a novel variant ryanodine receptor 2-E4005V.
Results:
The patients included 19 with catecholaminergic polymorphic ventricular tachycardia mono-phenotype and 5 catecholaminergic polymorphic ventricular tachycardia-left ventricular non-compaction overlap patients. The median age of onset symptoms was 9.0 (8.0,13.5) years. Most patients (91.7%) had cardiac symptoms, and 50% had a family history of syncope. Overlap patients had lower peak heart rate and threshold heart rate for ventricular tachycardia and ventricular premature beat during the exercise stress test (p < 0.05). Sudden cardiac death risk may be higher in overlap patients during follow-up. Gene sequencing revealed 1 novel ryanodine receptor 2 missense mutation E4005V and 1 mutation previously unreported in catecholaminergic polymorphic ventricular tachycardia, but no left ventricular non-compaction-causing mutations were observed. In-silico analysis showed the novel mutation E4005V broke down the interaction between two charged residues.
Conclusions:
Catecholaminergic polymorphic ventricular tachycardia overlapping with left ventricular non-compaction may lead to ventricular premature beat/ventricular tachycardia during exercise stress test at lower threshold heart rate than catecholaminergic polymorphic ventricular tachycardia alone; it may also indicate a worse prognosis and requires strict follow-up. ryanodine receptor 2 mutations disrupted interactions between residues and may interfere the function of ryanodine receptor 2.
Keywords
- Type
- Original Article
- Information
- Copyright
- © The Author(s), 2023. Published by Cambridge University Press
References
Sumitomo, N. Current topics in catecholaminergic polymorphic ventricular tachycardia. J Arrhythm 2016; 32: 344–351.CrossRefGoogle ScholarPubMed
Roston, TM, Yuchi, Z, Kannankeril, PJ, et al. The clinical and genetic spectrum of catecholaminergic polymorphic ventricular tachycardia: findings from an international multicentre registry. Europace 2018; 20: 541–547.CrossRefGoogle ScholarPubMed
Josephs, K, Patel, K, Janson, CM, Montagna, C, McDonald, TV. Compound heterozygous CASQ2 mutations and long-term course of catecholaminergic polymorphic ventricular tachycardia. Mol Genet Genomic Med 2017; 5: 788–794.CrossRefGoogle ScholarPubMed
Jenni, R, Oechslin, E, Schneider, J, Attenhofer Jost, C, Kaufmann, PA. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart 2001; 86: 666–671.CrossRefGoogle ScholarPubMed
Towbin, JA, Lorts, A, Jefferies, JL. Left ventricular non-compaction cardiomyopathy. Lancet 2015; 386: 813–825.CrossRefGoogle ScholarPubMed
Campbell, MJ, Czosek, RJ, Hinton, RB, Miller, EM. Exon 3 deletion of ryanodine receptor causes left ventricular noncompaction, worsening catecholaminergic polymorphic ventricular tachycardia, and sudden cardiac arrest. Am J Med Genet A 2015; 167A: 2197–2200.CrossRefGoogle ScholarPubMed
Landstrom, AP, Dobrev, D, Wehrens, XHT. Calcium signaling and cardiac arrhythmias. Circ Res 2017; 120: 1969–1993.CrossRefGoogle ScholarPubMed
Nozaki, Y, Kato, Y, Uike, K, et al. Co-phenotype of left ventricular non-compaction cardiomyopathy and atypical catecholaminergic polymorphic ventricular tachycardia in association with R169Q, a ryanodine receptor Type 2 Missense mutation. Circ J 2020; 84: 226–234.CrossRefGoogle ScholarPubMed
Szentpali, Z, Szili-Torok, T, Caliskan, K. Primary electrical disorder or primary cardiomyopathy? A case with a unique association of noncompaction cardiomyopathy and cathecolaminergic polymorphic ventricular tachycardia caused by ryanodine receptor mutation. Circulation 2013; 127: 1165–1166.CrossRefGoogle ScholarPubMed
Ohno, S, Omura, M, Kawamura, M, et al. Exon 3 deletion of RYR2 encoding cardiac ryanodine receptor is associated with left ventricular non-compaction. Europace 2014; 16: 1646–1654.CrossRefGoogle ScholarPubMed
Priori, SG, Wilde, AA, Horie, M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013; 10: 1932–1963.CrossRefGoogle ScholarPubMed
Oechslin, EN, Attenhofer Jost, CH, Rojas, JR, Kaufmann, PA, Jenni, R. Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol 2000; 36: 493–500.CrossRefGoogle ScholarPubMed
Pignatelli, RH, McMahon, CJ, Dreyer, WJ, et al. Clinical characterization of left ventricular noncompaction in children: a relatively common form of cardiomyopathy. Circulation 2003; 108: 2672–2678.CrossRefGoogle ScholarPubMed
Finsterer, J. Cardiogenetics, neurogenetics, and pathogenetics of left ventricular hypertrabeculation/noncompaction. Pediatr Cardiol 2009; 30: 659–681.CrossRefGoogle Scholar
van der Werf, C, Kannankeril, PJ, Sacher, F, et al. Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. J Am Coll Cardiol 2011; 57: 2244–2254.CrossRefGoogle ScholarPubMed
Richards, S, Aziz, N, Bale, S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med 2015; 17: 405–424.CrossRefGoogle ScholarPubMed
Shigemizu, D, Aiba, T, Nakagawa, H, et al. Exome analyses of long QT syndrome reveal candidate pathogenic mutations in Calmodulin-interacting genes. PLoS One 2015; 10: e0130329.CrossRefGoogle ScholarPubMed
Tiso, N, Stephan, DA, Nava, A, et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet 2001; 10: 189–194.CrossRefGoogle ScholarPubMed
Leenhardt, A, Denjoy, I, Guicheney, P. Catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol 2012; 5: 1044–1052.CrossRefGoogle Scholar
Roston, TM, AlAhmari, L, Krahn, AD, Sherwin, E, Sanatani, S. Choking-induced cardiac arrest unmasks a diagnosis of catecholaminergic polymorphic ventricular tachycardia. HeartRhythm case reports 2015; 1: 494–497.CrossRefGoogle ScholarPubMed
Kawata, H, Ohno, S, Aiba, T, et al. Catecholaminergic polymorphic ventricular tachycardia (CPVT) associated with ryanodine receptor (RyR2) gene mutations- long-term prognosis after initiation of medical treatment. Circ J 2016; 80: 1907–1915.CrossRefGoogle ScholarPubMed
Priori, SG, Carlo, N, Mirella, M, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002; 106: 69–74.CrossRefGoogle ScholarPubMed
Lahrouchi, N, Raju, H, Lodder, EM, et al. Utility of post-mortem genetic testing in cases of sudden arrhythmic death syndrome. J Am Coll Cardiol 2017; 69: 2134–2145.CrossRefGoogle ScholarPubMed
Olubando, D, Hopton, C, Eden, J, et al. Classification and correlation of RYR2 missense variants in individuals with catecholaminergic polymorphic ventricular tachycardia reveals phenotypic relationships. J Hum Genet 2020; 65: 531–539.CrossRefGoogle ScholarPubMed
Jiang, D, Wang, R, Xiao, B, et al. Enhanced store overload-induced Ca2+ release and channel sensitivity to luminal Ca2+ activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden death. Circ Res 2005; 97: 1173–1181.CrossRefGoogle ScholarPubMed
Acimovic, I, Refaat, MM, Moreau, A, et al. Post-translational modifications and diastolic calcium leak associated to the novel RyR2-D3638A mutation lead to CPVT in patient-specific hiPSC-derived cardiomyocytes. J Clin Med 2018; 7: 423.CrossRefGoogle Scholar
Roston, TM, Guo, W, Krahn, AD, et al. A novel RYR2 loss-of-function mutation (I4855M) is associated with left ventricular non-compaction and atypical catecholaminergic polymorphic ventricular tachycardia. J Electrocardiol 2017; 50: 227–233.CrossRefGoogle ScholarPubMed
Tang, Y, Tian, X, Wang, R, Fill, M, Chen, SR. Abnormal termination of Ca2+ release is a common defect of RyR2 mutations associated with cardiomyopathies. Circ Res 2012; 110: 968–977.CrossRefGoogle ScholarPubMed
Oechslin, E, Jenni, R. Left ventricular non-compaction revisited: a distinct phenotype with genetic heterogeneity? Eur Heart J 2011; 32: 1446–1456.CrossRefGoogle ScholarPubMed
Gourine, AV, Ackland, GL. Cardiac vagus and exercise. Physiology (Bethesda, Md) 2019; 34: 71–80.Google ScholarPubMed
Xu et al. supplementary material
File
31.8 KB