Catecholaminergic polymorphic ventricular tachycardia
Catecholaminergic polymorphic ventricular tachycardia | |
Classification and external resources | |
OMIM | 604772 611938 |
---|---|
DiseasesDB | 33816 |
Ventricular tachycardia Microchapters |
Differentiating Ventricular Tachycardia from other Disorders |
---|
Diagnosis |
Treatment |
Case Studies |
Catecholaminergic polymorphic ventricular tachycardia On the Web |
FDA on Catecholaminergic polymorphic ventricular tachycardia |
Catecholaminergic polymorphic ventricular tachycardia in the news |
Blogs on Catecholaminergic polymorphic ventricular tachycardia |
to Hospitals Treating Catecholaminergic polymorphic ventricular tachycardia |
Risk calculators and risk factors for Catecholaminergic polymorphic ventricular tachycardia |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: CPVT, Bidirectional tachycardia induced by catecholamines, Catecholamine-induced polymorphic ventricular tachycardia, Familial polymorphic ventricular tachycardia, FPVT
Overview
Catecholaminergic Polymorphic Ventricular Tachycardia is an inherited heart rhythm disorder caused by a mutation in voltage-gated ion channels which results in ventricular arrhythmias that are provoked by exercise or acute emotion. There are no associated structural abnormalities of the heart.
Historical Perspective
- Catecholaminergic polymorphic ventricular tachycardia (CPVT) was first described by Reid et al in 1975 and by Coumel et al in 1978.[1] It was described as a familial cardiac arrhythmia that occurs in patients with structurally normal heart and causes exercise or emotion triggered syncope and sudden death with a distinguishing pattern of ventricular and supraventricular arrhythmias.
- In 2001, Cardiac Ryanodine Receptor Gene (hRyR2) mutations were first identified in the pathogenesis of Catecholaminergic polymorphic ventricular tachycardia.[2]
- In 1995 and 2002, the clinical studies by Leenhardt et al and Priori et al, respectively, have contributed to the understanding of the natural history of CPVT.[3][4]
- In 2004, studies showed that RyR2 mutations reduced the threshold for Store-Overload-Induced Ca2+ Release (SOICR) and increased the tendency for triggered arrhythmia. Thus it appeared evident that catecholaminergic polymorphic ventricular tachycardia was caused by uncontrolled Ca2+ release from the sarcoplasmic reticulum.[5]
- In 2006, subsequent experimental studies demonstrated that the abnormal calcium release caused arrhythmias mediated by delayed afterdepolarizations and triggered activity.[6]
Epidemiology and Demographics
The incidence of CPVT is 10/100,000 people. CPVT is estimated to cause 15% of all unexplained sudden cardiac deaths in young people.
Pathophysiology
The voltage-gated ion channel mutation associated with CPVT intermittently causes the heart to develop polymorphic ventricular tachycardia in response to the natural release of catecholamines. Catecholaminergic polymorphic VT may have both autosomal dominant and autosomal recessive pattern of inheritance. The following genes are associated with CPVT:
- RYR2:
- Mutations in cardiac ryanodine receptor gene RyR2 accounts for CPVT 1, and majority of the cases (approximately 50-65%).[2][7]
- Genetic linkage studies revealed the disease-causing locus with an autosomal dominant inheritance pattern on chromosome 1q42–q43.[8]
- RyR2 is involved in intracellular calcium homeostasis and in the excitation-contraction coupling of the heart.
- Mutations in RYR2 cause uncontrolled calcium leakage from the sarcoplasmic reticulum during electrical diastole, with a subsequent increase in the cytosolic calcium concentration.[5][2]
- CASQ2:
- Mutations in cardiac calsequestrin gene CASQ2 accounts for CPVT 2, for approximately 2–5% of the CPVT cases.[9]
- The chromosome involved is located on 1p13.3-p11 with an autosomal recessive pattern of inheritance.
- CASQ2 is a Ca2+ buffering protein within the sarcoplasmic reticulum that plays a role in the control of calcium release from the sarcoplasmic reticulum to the cytosol.
The genes encoding cardiac ryanodine-calcium release channel RyR2 or, infrequently, cardiac calsequestrin CASQ2 are thus involved in the release of calcium from the sarcoplasmic reticulum and mutations therein result in inappropriate calcium leak from the sarcoplasmic reticulum.[5][10][11] The cytosolic calcium overload activates the sodium-calcium exchanger, leading to a transient inward current, and delayed after-depolarizations that in turn can lead to triggered arrhythmias, particularly under conditions of high β-adrenergic tone.[12][13]
Type | OMIM | Gene | Locus |
---|---|---|---|
CPVT1 | 604772 | RYR2 | 1q42.1-q43 |
CPVT2 | 611938 | CASQ2 | 1p13.3-p11 |
Natural History, Complications, Prognosis
The majority of events occur during childhood and more than 60% of affected individuals will have a first episode of syncope or cardiac arrest by age 20. The polymorphic ventricular tachycardia may self-terminate or it may degenerate into ventricular fibrillation, causing sudden cardiac death.
Diagnosis
Symptoms
The most common symptom is syncope, as a result of exercise-induced ventricular arrhythmias which occur during physical activity or acute emotion.[14] The symptoms usually appear during the first or second decade of life.
Electrocardiogram
The resting electrocardiogram is usually unremarkable but can show sinus bradycardia and a prominent U wave.
Exercise Stress Testing
CPVT is diagnosis based on reproducing ventricular arrhythmias during exercise stress testing, syncope occurring during physical activity and acute emotion, and a history of exercise or emotion-related palpitations and dizziness with an absence of structural cardiac abnormalities.
Genetic Testing
Genetic testing is available in some locations and may be useful in diagnosing the presence of the genetic disorder among related individuals before the onset of aborted sudden death or sudden cardiac death.
Treatment
CPVT is treated with beta blockers, verapamil or an ICD (implantable cardiac defibrillator).
Pharmacotherapy
Medications to treat CPVT include beta blockers and verapamil.[15]
According to recent research published in Nature Medicine, flecainide inhibits the release of the cardiac ryanodine receptor–mediated Ca2+, and is therefore believed to medicate the underlying molecular cause of CPVT in both mice and humans.[16]
Implantable cardioverter-defibrillator
Implantable cardioverter-defibrillators are used to prevent sudden death.
Sympathectomy
In recent reports, left cardiac sympathetic denervation and bilateral thoracoscopic sympathectomy have shown promising results in individuals whose symptoms cannot be controlled by beta blockers.[17]
ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death (DO NOT EDIT) [18]
Class I |
"1. Beta blockers are indicated for patients who are clinically diagnosed with CPVT on the basis of the presence of spontaneous or documented stress-induced ventricular arrhythmias. (Level of Evidence: C)" |
"2. Implantation of an ICD with use of beta blockers is indicated for patients with CPVT who are survivors of cardiac arrest and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)" |
Class IIa |
"1. Beta blockers can be effective in patients without clinical manifestations when the diagnosis of CPVT is established during childhood based on genetic analysis. (Level of Evidence: C)" |
"2. Implantation of an ICD with the use of beta blockers can be effective for affected patients with CPVT with syncope and/or documented sustained VT while receiving beta blockers and who have reasonable expectation of survival with a good functional status for more than 1 y. (Level of Evidence: C)" |
Class IIb |
"1. Beta blockers may be considered for patients with CPVT who were genetically diagnosed in adulthood and never manifested clinical symptoms of tachyarrhythmias. (Level of Evidence: C)" |
References
- ↑ Reid, D S; Tynan, M; Braidwood, L; Fitzgerald, G R (1975). "Bidirectional tachycardia in a child. A study using His bundle electrography". Heart. 37 (3): 339–344. doi:10.1136/hrt.37.3.339. ISSN 1355-6037.
- ↑ 2.0 2.1 2.2 Priori, Silvia G.; Napolitano, Carlo; Tiso, Natascia; Memmi, Mirella; Vignati, Gabriele; Bloise, Raffaella; Sorrentino, Vincenzo; Danieli, Gian Antonio (2001). "Mutations in the Cardiac Ryanodine Receptor Gene (
hRyR2
) Underlie Catecholaminergic Polymorphic Ventricular Tachycardia". Circulation. 103 (2): 196–200. doi:10.1161/01.CIR.103.2.196. ISSN 0009-7322. line feed character in
|title=
at position 51 (help) - ↑ Leenhardt, Antoine; Lucet, Vincent; Denjoy, Isabelle; Grau, Francis; Ngoc, Dien Do; Coumel, Philippe (1995). "Catecholaminergic Polymorphic Ventricular Tachycardia in Children". Circulation. 91 (5): 1512–1519. doi:10.1161/01.CIR.91.5.1512. ISSN 0009-7322.
- ↑ Priori, Silvia G.; Napolitano, Carlo; Memmi, Mirella; Colombi, Barbara; Drago, Fabrizio; Gasparini, Maurizio; DeSimone, Luciano; Coltorti, Fernando; Bloise, Raffaella; Keegan, Roberto; Cruz Filho, Fernando E.S.; Vignati, Gabriele; Benatar, Abraham; DeLogu, Angelica (2002). "Clinical and Molecular Characterization of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia". Circulation. 106 (1): 69–74. doi:10.1161/01.CIR.0000020013.73106.D8. ISSN 0009-7322.
- ↑ 5.0 5.1 5.2 Jiang, D.; Xiao, B.; Yang, D.; Wang, R.; Choi, P.; Zhang, L.; Cheng, H.; Chen, S. R. W. (2004). "RyR2 mutations linked to ventricular tachycardia and sudden death reduce the threshold for store-overload-induced Ca2+ release (SOICR)". Proceedings of the National Academy of Sciences. 101 (35): 13062–13067. doi:10.1073/pnas.0402388101. ISSN 0027-8424.
- ↑ Liu, Nian; Colombi, Barbara; Memmi, Mirella; Zissimopoulos, Spyros; Rizzi, Nicoletta; Negri, Sara; Imbriani, Marcello; Napolitano, Carlo; Lai, F. Anthony; Priori, Silvia G. (2006). "Arrhythmogenesis in Catecholaminergic Polymorphic Ventricular Tachycardia". Circulation Research. 99 (3): 292–298. doi:10.1161/01.RES.0000235869.50747.e1. ISSN 0009-7330.
- ↑ Ackerman, M. J.; Priori, S. G.; Willems, S.; Berul, C.; Brugada, R.; Calkins, H.; Camm, A. J.; Ellinor, P. T.; Gollob, M.; Hamilton, R.; Hershberger, R. E.; Judge, D. P.; Le Marec, H.; McKenna, W. J.; Schulze-Bahr, E.; Semsarian, C.; Towbin, J. A.; Watkins, H.; Wilde, A.; Wolpert, C.; Zipes, D. P. (2011). "HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies: This document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA)". Europace. 13 (8): 1077–1109. doi:10.1093/europace/eur245. ISSN 1099-5129.
- ↑ Swan, Heikki; Piippo, Kirsi; Viitasalo, Matti; Heikkilä, Päivi; Paavonen, Timo; Kainulainen, Katariina; Kere, Juha; Keto, Pekka; Kontula, Kimmo; Toivonen, Lauri (1999). "Arrhythmic disorder mapped to chromosome 1q42–q43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts". Journal of the American College of Cardiology. 34 (7): 2035–2042. doi:10.1016/S0735-1097(99)00461-1. ISSN 0735-1097.
- ↑ Lahat, Hadas; Pras, Elon; Olender, Tsviya; Avidan, Nili; Ben-Asher, Edna; Man, Orna; Levy-Nissenbaum, Etgar; Khoury, Asad; Lorber, Avraham; Goldman, Boleslaw; Lancet, Doron; Eldar, Michael (2001). "A Missense Mutation in a Highly Conserved Region of CASQ2 Is Associated with Autosomal Recessive Catecholamine-Induced Polymorphic Ventricular Tachycardia in Bedouin Families from Israel". The American Journal of Human Genetics. 69 (6): 1378–1384. doi:10.1086/324565. ISSN 0002-9297.
- ↑ di Barletta, Marina Raffaele; Viatchenko-Karpinski, Serge; Nori, Alessandra; Memmi, Mirella; Terentyev, Dmitry; Turcato, Federica; Valle, Giorgia; Rizzi, Nicoletta; Napolitano, Carlo; Gyorke, Sandor; Volpe, Pompeo; Priori, Silvia G. (2006). "Clinical Phenotype and Functional Characterization of
CASQ2
Mutations Associated With Catecholaminergic Polymorphic Ventricular Tachycardia". Circulation. 114 (10): 1012–1019. doi:10.1161/CIRCULATIONAHA.106.623793. ISSN 0009-7322. line feed character in
|title=
at position 54 (help) - ↑ Lehnart, Stephan E.; Wehrens, Xander H.T.; Laitinen, Päivi J.; Reiken, Steven R.; Deng, Shi-Xiang; Cheng, Zhenzhuang; Landry, Donald W.; Kontula, Kimmo; Swan, Heikki; Marks, Andrew R. (2004). "Sudden Death in Familial Polymorphic Ventricular Tachycardia Associated With Calcium Release Channel (Ryanodine Receptor) Leak". Circulation. 109 (25): 3208–3214. doi:10.1161/01.CIR.0000132472.98675.EC. ISSN 0009-7322.
- ↑ Cerrone, Marina; Noujaim, Sami F.; Tolkacheva, Elena G.; Talkachou, Arkadzi; O’Connell, Ryan; Berenfeld, Omer; Anumonwo, Justus; Pandit, Sandeep V.; Vikstrom, Karen; Napolitano, Carlo; Priori, Silvia G.; Jalife, José (2007). "Arrhythmogenic Mechanisms in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia". Circulation Research. 101 (10): 1039–1048. doi:10.1161/CIRCRESAHA.107.148064. ISSN 0009-7330.
- ↑ Knollmann, B. C. (2006). "Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia". Journal of Clinical Investigation. doi:10.1172/JCI29128. ISSN 0021-9738.
- ↑ Napolitano, Carlo (May 2007). "Diagnosis and treatment of catecholaminergic polymorphic ventricular tachycardia" (PDF). Heart Rhythm. 4 (5): 675–8. doi:10.1016/j.hrthm.2006.12.048. PMID 17467641. Retrieved 2008-12-17. Unknown parameter
|coauthors=
ignored (help)[dead link] - ↑ Sumitomo, Naokata (January 2003). "Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death". Heart. 89 (1): 66–70. doi:10.1136/heart.89.1.66. PMC 1767500. PMID 12482795. Unknown parameter
|coauthors=
ignored (help) - ↑ Watanabe, Hiroshi (2009-04-01). "Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans". Nature Medicine. 15 (4): 380–383. doi:10.1038/nm.1942. PMC 2904954. PMID 19330009. Retrieved 2009-05-04. Unknown parameter
|coauthors=
ignored (help) - ↑ Scott, P.A. (October 2008). "Successful treatment of catecholaminergic polymorphic ventricular tachycardia with bilateral thoracoscopic sympathectomy". Heart Rhythm. 5 (10): 1461–1463. doi:10.1016/j.hrthm.2008.07.007. PMID 18760972. Unknown parameter
|coauthors=
ignored (help) - ↑ Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M; et al. (2006). "ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society". Circulation. 114 (10): e385–484. doi:10.1161/CIRCULATIONAHA.106.178233. PMID 16935995.
- CS1 errors: invisible characters
- Pages with citations using unsupported parameters
- All articles with dead external links
- Articles with dead external links from September 2010
- Articles with invalid date parameter in template
- CS1 maint: Explicit use of et al.
- CS1 maint: Multiple names: authors list
- Cardiology