Catecholaminergic Polymorphic Ventricular Tachycardia

Introduction

Simply stated, “Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease characterized by cardiac electrical instability exacerbated by acute activation of the adrenergic nervous system.”¹ On a cellular level, there is a reduction in “...the extent and shortening the duration of calcium signaling refractoriness, thereby promoting untimely sarcoplasmic reticulum calcium release and arrhythmogenic delayed afterdepolarizations in cardiac myocytes.”² Since this anomaly is genetic in nature, cardiac angiography and myocardial biopsy are usually normal in CPVT patients.³

The inherited mutation is often RYR2 (autosomal dominant) or CASQ2 (autosomal recessive), although other mutations may exist.¹ The most common mutation seen in CPVT is the RYR2 gene. CPVT can be manifested as early as infancy, as in some cases of SIDS; however, mean onset age is between seven and nine years old.¹ There have been reported cases where symptoms were not manifested until adulthood, as is the case with our EP study patient discussed here.

CPVT is manifested most often during exercise, intense emotional states, or during periods of high stress.¹ The release of the catecholamines elicit the cardiac electrical instability and polymorphic ventricular tachycardia as seen on EKG.  

Case Description

Our patient is a 48-year-old male. Dr. Khan began his investigation with a thorough history and physical, which revealed patient complaints of intermittent palpitations over the previous four months. Around the same time, the patient began an exercise routine and had one episode of lightheadedness followed by a brief episode of unconsciousness at home. The patient’s only known history is hypertension.

An echocardiogram was performed, which revealed normal left ventricular systolic function at 66%. A 30-day event monitor revealed several episodes of nonsustained ventricular tachycardia (NSVT) that were associated with symptoms. The initial EKG showed normal sinus rhythm with normal QT and PR intervals. An exercise stress test was subsequently performed. 

Due to the inducible nature of a treadmill test with CVPT, it is often considered the best diagnostic tool.¹ The patient exercised according to the Bruce protocol for 11 minutes and 59 seconds. The test was stopped due to achieving target heart rate. The conclusion of the exercise stress test revealed no ischemia; however, the patient had several runs of NSVT in recovery that subsided in about three minutes (5 mg of Lopressor was given IV). An electrophysiology study was then ordered to confirm and validate the short duration of the VT stress test finding. 

The electrophysiology study was done with the usual right atrium, HIS, and right ventricular catheter placement. Baseline measurements were normal with a cycle length of 870 ms, PR interval of 207 ms, QRS of 63 ms, QT interval of 401 ms, AH interval of 90 ms, and HV interval of 47 ms. The sinus node recovery time at 600 ms was 960 ms. The AV Wenckebach cycle length was 370 ms with PR greater than RR. The atrial ERP at 600 ms was 310 ms. There was no AH jump. EP protocol of pacing RVA and RVOT with up to four extra stimuli using two different drive cycle lengths did not induce VT. We subsequently gave Isuprel and the patient was inducible at 400/300/280 ms. The tachycardia cycle length was 230 ms, induced spontaneously during drive cycle train. The tachycardia had alternating left bundle and intraventricular conduction delay (IVCD) morphology. This tachycardia was pace terminated by pacing at 200 ms. The impression of the EPS revealed normal sinus node and AV node function with no pathways. Electrical stimulation did not induce any sustained ventricular tachycardia. The tachycardia was induced after beta antagonist stimulation with Isuprel intravenously. Due to the alternating morphology, CVPT is suggestive. The patient was then treated with intravenous beta-blockers. 

Beta-blockers are indicated for treatment for all patients affected with this mutation, including those without a syncopal event.¹ “Beta-blockers reduce arrhythmias, but in 30% of patients an implantable defibrillator may be required.”⁴ 

Once a patient has reached therapeutic beta-blocker protection, it is recommended to have the patient undergo a follow-up stress test. Our patient underwent his follow-up stress test approximately three weeks after his EPS. His home medication regimen included metoprolol 50 mg daily, omeprazole 20 mg daily, and Zestoretic 20/12.5 md daily. The impression of his outpatient follow-up stress test was a normal stress test with no evidence of ischemia, good exercise capacity, and no significant ventricular tachyarrhythmias. It appeared beta-blocker therapy at the current dose was effective in suppressing the ventricular tachyarrhythmia.

Due to the nature of this being a genetic mutation, the patient elected to have genetic testing completed. If the results are positive, the patient will also have genetic testing for his two young sons.

Summary

It is with thorough skills of investigation combined with a wide knowledge base that we are able to use the tools we have to properly diagnose and treat patients appropriately. It is also with great appreciation we were able to obtain the patient’s follow-up information after the EPS in order to learn and thoroughly understand the details of this potentially life-threatening disorder. 

Disclosure: The authors have no conflicts of interest to report. 

References

1. Napolitano C, Priori SG, Bloise R. Catecholaminergic Polymorphic Ventricular Tachycardia, February 16, 2012. Available online at www.ncbi.nlm.nih.gov/books/NBK1289. Accessed January 18, 2013. 
2. Györke S. Molecular basis of catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm. 2009 Jan;6(1):123-9. doi: 10.1016/j.hrthm.2008.09.013. Epub 2008 Sep 16.
3. Pizzale SG, Gollob MH, Gow R, Birnie DH. Sudden death in a young man with catecholaminergic polymorphic ventricular tachycardia and paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 2008;19:1319-1321.
4. Priori SG, Napolitano C, Memmi M, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation. 2002 Jul 2;106(1):69-74.