CPVTNext

CPVTNextTM is a multi-gene panel for patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). It includes RYR2, in which mutations have been identified in over 50% of cases. Often, CPVT is asymptomatic and sudden death is the first symptom. Therefore, genetic testing may be the most effective way of identifying at-risk individuals or confirming a diagnosis.

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CPVTNextTM is a multi-gene panel for patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). It includes RYR2, in which mutations have been identified in over 50% of cases. Often, CPVT is asymptomatic and sudden death is the first symptom. Therefore, genetic testing may be the most effective way of identifying at-risk individuals or confirming a diagnosis.

CPVTNext is a next generation sequencing (NGS) and deletion/duplication panel of six genes associated with CPVT: ANK2, CALM1, CASQ2, KCNJ2, RYR2, and TRDN. These genes are also included in the comprehensive inherited arrhythmia (RhythmNext) and comprehensive cardiovascular genetics (CardioNext) panels. 

Disease Name 
Catecholaminergic polymorphic ventricular tachycardia (CPVT)
Disease Information 

CPVT occurs in approximately 1 in 10,000 individuals worldwide and is characterized by syncope, often occurring during exercise or acute emotion.  These arrhythmias may spontaneously resolve, or progress and lead to sudden cardiac arrest.  Age of onset is typically between 7-12 years of age, and there is up to a 30% lifetime risk for cardiac arrest, if untreated.  CPVT can be inherited in an autosomal dominant or autosomal recessive manner. An exercise stress test is usually necessary for diagnosis, as it is needed to evoke the typical arrhythmia.

Management for CPVT typically includes resting electrocardiogram (EKG), exercise stress test, Holter monitoring, and assessment of sudden cardiac death risk.  Specific medication use for those clinically affected or with an RYR2 mutation but clinically unaffected (no history of syncope, cardiac events, or ventricular arrhythmias on exercise stress testing) are very important, since sudden death can be the first manifestation of the disease.  Implantable cardioverter defibrillator (ICD) or pacemaker placement may be recommended if arrhythmias are not well controlled, or if a patient is at high risk of sudden cardiac death.  Holter monitoring may help to document catecholamine-related arrhythmias.  CPVT may present in childhood, so medical therapy can be considered in children and adults at high risk for CPVT.

 

Genes Implicated in Catecholaminergic Polymorphic Ventricular Tachycardia

genes implicated in catecholaminergic polymorphic ventricular tachycardia ryr2, casq2

 

2011 Heart Rhythm Society and European Heart Rhythm Association Expert Consensus Statement 

  • Genetic testing is a Class I recommendation for patients with a clinical suspicion for CPVT
  • Once a pathogenic gene mutation is identified in a family, mutation-specific testing of family members is a Class I recommendation

 

 

Testing Benefits & Indication 
  • Clarify diagnosis and risk for sudden cardiac arrest 
  • Target medical management and prevention of cardiac arrest and other complications
  • Offer family members genetic testing (for a familial mutation) and implement medical surveillance to only those that need it 
  • Reduce healthcare costs, resources, and anxiety for families
Test Description 

CPVTNext includes 6 genes associated with CPVT (listed above). These genes are also included in the comprehensive arrhythmia (RhythmNext) and comprehensive cardiovascular genetics (CardioNext) panels. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes, followed by polymerase chain reaction (PCR) and NGS. Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Reportable small insertions and deletions, potentially homozygous variants, variants in regions complicated by pseudogene interference, and single nucleotide variant calls not satisfying 100x depth of coverage and 40% het ratio thresholds are verified by Sanger sequencing. This assay targets all coding domains and well into the flanking 5’ and 3’ ends of all the introns and untranslated regions. Gross deletion/duplication analysis for available genes is performed utilizing a targeted chromosomal microarray.

Mutation Detection Rate 

CPVTNext will find a mutation in 50-60% of patients with CPVT (clinical sensitivity).  CPVTNext can detect >99.9% of described mutations in the included genes (analytic sensitivity).

Specimen Requirements 

Complete specimen requirements are available here or by downloading the PDF found above on this page.

Turnaround Time 
TEST CODE TEST NAME TURNAROUND TIME (Weeks)
8902 CPVTNext 4-5
8900 RhythmNextTM  4-5
8910 CardioNextTM 4-5 
8911 CardioNext + TTN 4-5 
9520 CustomNext-Cardio
Up to 106 cardiovascular genes of your choice
4-5 weeks

 

Specialty 
Genes 
RYR2
ANK2
CALM1
CASQ2
KCNJ2
TRDN
Tests 
References 
  1. Adapted from Ackerman MJ et al. HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies. Heart Rhythm. 2011 Aug;8(8):1308-39. 
  2. Napolitano C, Priori SG, Bloise R. Catecholaminergic Polymorphic Ventricular Tachycardia. 2004 Oct 14 [Updated 2014 Mar 6]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. 
  3. Mu W, et al. Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing. J Mol Diagn. 2016. 18(6):923-932.