Catecholaminergic polymorphic ventricular tachycardia: Difference between revisions
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==Pathophysiology== | ==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]]. CPVT has an autosomal dominant inheritance pattern. There are two genes currently associated with CPVT: | 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]]. CPVT has an autosomal dominant inheritance pattern. There are two genes currently associated with CPVT: | ||
*[[RYR2]]: Responsible for the majority of cases. The Ryanodine receptor ([[RYR2]]) is involved in intracardiac Ca2+ handling. Ca2+ overload triggers abnormal cardiac activity.<ref>{{cite journal |author=Wehrens XH, Marks AR |title=Sudden unexplained death caused by cardiac ryanodine receptor (RyR2) mutations |journal=Mayo Clin. Proc. |volume=79 |issue=11 |pages=1367–71 |year=2004 |month=November |pmid=15544013 |doi= 10.4065/79.11.1367|url=http://www.mayoclinicproceedings.com/inside.asp?AID=711&UID= |format= }} {{dead link|date=May 2009}}</ref> | *[[RYR2]]: Responsible for the majority of cases. The Ryanodine receptor ([[RYR2]]) is involved in intracardiac Ca2+ handling. Ca2+ overload triggers abnormal cardiac activity.<ref>{{cite journal |author=Wehrens XH, Marks AR |title=Sudden unexplained death caused by cardiac ryanodine receptor (RyR2) mutations |journal=Mayo Clin. Proc. |volume=79 |issue=11 |pages=1367–71 |year=2004 |month=November |pmid=15544013 |doi= 10.4065/79.11.1367|url=http://www.mayoclinicproceedings.com/inside.asp?AID=711&UID= |format= }} {{dead link|date=May 2009}}</ref> Mutation of RYR2 is inherited in an autosomal dominant fashion. | ||
*[[CASQ2]]: Responsible for 1-2% of cases. Calsequestrin ([[CASQ2]]) is a calcium buffering protein of the [[sarcoplasmic reticulum]]. | *[[CASQ2]]: Responsible for 1-2% of cases. Calsequestrin ([[CASQ2]]) is a calcium buffering protein of the [[sarcoplasmic reticulum]]. The inheritance of the Calsequestrin-2 mutation is autosomal recessive. | ||
{| class="wikitable" | {| class="wikitable" | ||
Revision as of 01:12, 15 October 2012
| Catecholaminergic polymorphic ventricular tachycardia | |
| Classification and external resources | |
| OMIM | 604772 611938 |
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| DiseasesDB | 33816 |
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Ventricular tachycardia Microchapters |
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Differentiating Ventricular Tachycardia from other Disorders |
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Diagnosis |
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Treatment |
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Case Studies |
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Catecholaminergic polymorphic ventricular tachycardia On the Web |
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FDA on Catecholaminergic polymorphic ventricular tachycardia |
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Catecholaminergic polymorphic ventricular tachycardia in the news |
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Blogs on Catecholaminergic polymorphic ventricular tachycardia |
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to Hospitals Treating Catecholaminergic polymorphic ventricular tachycardia |
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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
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
The disorder was first recognized in 1975.
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. CPVT has an autosomal dominant inheritance pattern. There are two genes currently associated with CPVT:
- RYR2: Responsible for the majority of cases. The Ryanodine receptor (RYR2) is involved in intracardiac Ca2+ handling. Ca2+ overload triggers abnormal cardiac activity.[1] Mutation of RYR2 is inherited in an autosomal dominant fashion.
- CASQ2: Responsible for 1-2% of cases. Calsequestrin (CASQ2) is a calcium buffering protein of the sarcoplasmic reticulum. The inheritance of the Calsequestrin-2 mutation is autosomal recessive.
| 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. 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.
Diagnosis
CPVT diagnosis is 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.[2]
Treatment
CPVT is treated with beta blockers, verapamil or an ICD (implantable cardiac defibrillator).
Pharmacotherapy
Medications to treat CPVT include beta blockers and verapamil.[3]
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.[4]
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.[5][6][7][clarification needed]
ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death (DO NOT EDIT) [8]
Recommendations for Catecholaminergic Polymorphic Ventricular Tachycardia
| 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 stressinduced 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
- ↑ Wehrens XH, Marks AR (2004). "Sudden unexplained death caused by cardiac ryanodine receptor (RyR2) mutations". Mayo Clin. Proc. 79 (11): 1367–71. doi:10.4065/79.11.1367. PMID 15544013. Unknown parameter
|month=ignored (help) [dead link] - ↑ 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) - ↑ Invalid
<ref>tag; no text was provided for refs namednejm - ↑ Hughes, Sue (2008-05-07). "Denervation successfully treats catecholaminergic polymorphic ventricular tachycardia". HeartWire. WebMD. Retrieved 2008-12-17.
- ↑ 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.
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