Catecholaminergic polymorphic ventricular tachycardia overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mounika Reddy Vadiyala, M.B.B.S.[2]
Overview
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT is a rare inherited arrhythmogenic disorder characterized by syncopal attacks, ventricular arrhythmias, and even sudden cardiac death, mostly in young patients. It is caused by mutations in calcium handling proteins such as RyR2 and CASQ2 within the sarcoplasmic reticulum, which results in ventricular arrhythmias in the setting of a high adrenergic tone such as during physical exercise or strong emotions. Since it is caused by mutations in genes encoding for channel-proteins that regulate cardiac electrical activity, CPVT is referred to as a channelopathy. There are no associated structural abnormalities of the heart in catecholaminergic polymorphic ventricular tachycardia.
Historical Perspective
Catecholaminergic polymorphic ventricular tachycardia (CPVT) was first described by Reid et al in 1975. 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 (RyR2) mutations were first implicated in the pathogenesis of catecholaminergic polymorphic ventricular tachycardia (CPVT). Subsequent experimental studies demonstrated that the abnormal calcium release from the sarcoplasmic reticulum caused arrhythmias mediated by delayed afterdepolarizations and triggered activity.
Classification
Catecholaminergic polymorphic ventricular tachycardia can be classified based upon the underlying pathogenic mutation.
Pathophysiology
Catecholaminergic polymorphic ventricular tachycardia is caused by mutations in genes encoding channel proteins that regulate the cardiac electrical function, resulting in inappropriate calcium leak from the sarcoplasmic reticulum during electrical diastole and thus leading to triggered arrhythmias, in the absence of structural cardiac abnormalities. CPVT is thus an inherited disorder and may have both autosomal dominant and autosomal recessive pattern of inheritance. Genes associated with CPVT include RYR2, CASQ2, CALM1 and TRDN.
Causes
Catecholaminergic polymorphic ventricular tachycardia is a genetic disorder. It is caused by mutations in the genes such as RYR2, CASQ2, CALM1 and TRDN.
Differentiating Catecholaminergic polymorphic ventricular tachycardia from other Diseases
Catecholaminergic polymorphic ventricular tachycardia must be differentiated from Arrhythmogenic right ventricular dysplasia, Short-coupled ventricular tachycardia (SC-torsade de pointes [TdP]), Long QT syndrome and Andersen-Tawil syndrome.
Epidemiology and Demographics
Catecholaminergic polymorphic ventricular tachycardia is a rare disorder with the prevalence estimated to be 1 per 10,000 individuals. CPVT is more common among young individuals.
Risk factors
Possible risk factors in the development of catecholaminergic polymorphic ventricular tachycardia (CPVT) include young age, exercise, stress, family history of syncope or sudden death, and family history of CPVT.
Screening
There is insufficient evidence to recommend routine screening for Catecholaminergic polymorphic ventricular tachycardia. But screening among relatives is indicated when a likely pathogenetic mutation is identified in clinically affected index cases. Screening methods for CPVT are exercise stress testing and genetic testing.
Natural History, Complications and Prognosis
If left untreated, approximately 30% of patients experience at least one cardiac arrest and up to 80% one or more syncopal spells. Common complications of catecholaminergic polymorphic ventricular tachycardia include ventricular fibrillation, sudden cardiac arrest, and sudden cardiac death. Prognosis is generally poor, and the 10-year mortality of patients with catecholaminergic polymorphic ventricular tachycardia is approximately 40%.
Diagnosis
History and symptoms
Syncope triggered by exercise or emotion is the initial manifestation in the majority of the cases of catecholaminergic polymorphic ventricular tachycardia. Sudden cardiac death during exercise or emotion may also be the initial manifestation in a relevant proportion of cases. Most of the patients have a positive family history of CPVT or sudden cardiac death.
Physical examination
Patients with catecholaminergic polymorphic ventricular tachycardia usually appear normal. Physical examination should include thorough cardiovascular examination, lung examination, and close monitoring of vital signs.
Laboratory findings
There are no diagnostic laboratory findings associated with catecholaminergic polymorphic ventricular tachycardia.
Electrocardiogram
Catecholaminergic polymorphic ventricular tachycardia patients usually have a normal resting ECG. However, in a subset of patients, sinus bradycardia, prominent U-waves, and supraventricular arrhythmias are seen.
Exercise Stress Testing
Exercise Stress Testing is the primary diagnostic test and the most helpful clinical tool in diagnosing CPVT as it can reproducibly evoke the typical ventricular tachycardia during acute adrenergic activation (exercise). During exercise stress testing, sinus rhythm accelerates and beyond a heart rate of 120-130 beats per minute, isolated and often monomorphic ventricular premature beats (VPBs) typically occur first and then increase with heart rate to bigeminy. Subsequently, the VPBs become polymorphic or bidircetional, and as the exercise increase, they form bursts of non-sustained polymorphic ventricular tachycardia or bidirectional ventricular tachycardia (VT). With continuous activity, the arrhythmia persists and becomes more rapid, eventually assuming the appearance of polymorphic ventricular tachycardia (VT), which is very fast, fibrillation-like and leads to syncope. The arrhythmias disappear on stopping the exercise. Bidirectional ventricular tachycardia (VT) is the hallmark finding of catecholaminergic polymorphic ventricular tachycardia.
Genetic Testing
Genetic testing helps in the confirmation of the diagnosis of catecholaminergic polymorphic ventricular tachycardia. It allows the identification of mutations in up to 65% of patients with a clinical diagnosis of CPVT. There are HRS/EHRA Expert Consensus Recommendations for Genetic testing in Catecholaminergic polymorphic ventricular tachycardia.
X-ray
There are no x-ray findings associated with catecholaminergic polymorphic ventricular tachycardia.
Echocardiography/Ultrasound
There are no echocardiography/ultrasound findings associated with catecholaminergic polymorphic ventricular tachycardia.
CT scan
There are no CT scan findings associated with catecholaminergic polymorphic ventricular tachycardia.
MRI
There are no MRI findings associated with catecholaminergic polymorphic ventricular tachycardia.
Other Imaging Findings
There are no other imaging findings associated with Catecholaminergic polymorphic ventricular tachycardia.
Other Diagnostic Studies
Other diagnostic studies for catecholaminergic polymorphic ventricular tachycardia include epinephrine infusion and holter monitoring. In patients who cannot perform an exercise stress test, epinephrine infusion and Holter monitoring help to establish the diagnosis of CPVT.
Treatment
Medical Therapy
Pharmacologic medical therapies for CPVT include beta blockers, flecainide and verapamil. Beta blockers remain the first-line therapeutic option for all the patients with catecholaminergic polymorphic ventricular tachycardia.
Implantable Cardioverter-Defibrillator
Implantable cardioverter defibrillator should be used with pharmacologic therapy. It is recommended in patients who are at high risk of cardiac arrest, patients who have survived a sudden cardiac arrest and patients who have experienced syncope or sustained VT despite optimal medical therapy.
Surgery
Surgery is not the first-line treatment option for patients with catecholaminergic polymorphic ventricular tachycardia. Sympathectomy or left cardiac sympathetic denervation is usually reserved for patients who experience recurrent symptoms and/or implantable cardioverter-defibrillator (ICD) shocks despite optimal medical therapy or in those who are intolerant or have contraindications to beta blockers
Prevention
There are no established measures for the primary prevention of catecholaminergic polymorphic ventricular tachycardia. However, episodes of syncope and sudden cardiac arrest can be prevented with lifestyle modifications, holter monitoring and compliance with medical therapy.