catecholaminergic polymorphic ventricular tachycardia ( cpvt ) is an inherited arrhythmogenic disease that can cause syncope or sudden cardiac death during emotional or physical stress in the absence of detectable structural heart disease and a prolonged qt interval on an electrocardiogram ( ecg ) .
mutations in two genes , the cardiac ryanodine receptor gene ( ryr2 ) and calsequestrin 2 gene ( casq2 ) , have been identified in patients with cpvt .
these mutations lead to an increase in intracellular ca concentration , resulting in life - threatening ventricular arrhythmias , possibly via delayed depolarizations .
a 16-year - old male , who had suffered from recurrent episodes of syncope triggered by physical exertion was referred to our hospital after undergoing defibrillation at a local emergency department ( ed ) .
he had lost consciousness at school during a volleyball test that was also emotionally stressful .
an initial ecg at a local ed revealed ventricular fibrillation . although his arrhythmia was converted to sinus rhythm after defibrillation , the patient was stuporous and had repeated episodes of nonsustained ventricular tachycardia ( vt ) .
after referral to our hospital , ecg monitoring in the ed and intensive care unit showed intermittent nonsustained vt and bidirectional vt ( fig .
when the patient became agitated , his heart rate increased , and the ecg showed nonsustained polymorphic vt despite intravenous administration of a -blocker . he was sedated and placed on mechanical ventilation .
two days later , his heart rate was regular , and no additional episodes of vt were observed .
his ecg showed a sinus rhythm with a corrected qt interval of 423 msec ( fig .
2 ) . routine laboratory findings , including electrolytes and two - dimensional echocardiography , were unremarkable . a detailed history of the patient included several episodes of syncope since the age of 8 years associated with physical activities , such as sprinting , playing football , and fighting with a sibling .
his father also experienced an episode of syncope associated with sprinting at the age of 9 years .
the patient and his family underwent a genetic analysis , and his father and mother each had one different de novo missense mutation in ryr2 ( exon 97 c.14009t > a p.l4670h in the father and exon 37 c.5428g > c p.v1810l in the mother ) .
as his episodes of syncope were associated with sympathetic activation , an exercise ecg test and epinephrine infusion test ( intravenous bolus of 0.1 g / kg followed by continuous infusion at rates of 0.1 g / kg per minute ) were performed .
however , only premature ventricular complex ( pvc ) bigeminy was induced with no episodes of syncope during the exercise ecg test ( fig .
3 ) and epinephrine only increased his heart rate without an arrhythmia . with these clinical features , we made the diagnosis of cpvt .
atenolol ( 37.5 mg bid ; 1.9 mg / kg / day ) was prescribed , and a follow - up exercise ecg test while on the -blocker was performed 3 days later . during the follow - up exercise ecg test
the patient remains on 50 mg bid atenolol ( 2.3 mg / kg / day ) and is being followed . to date
catecholaminergic polymorphic ventricular tachycardia , arrhythmogenic right ventricular cardiomyopathy , and long qt syndrome are well known causes of exercise - induced syncope that commonly manifest normal baseline ecgs.1)2 ) therefore , many provocation tests , including vt induction , an exercise ecg test , and epinephrine infusion tests , have been used to diagnose exercise - induced syncope.1)2 ) exercise - induced bidirectional vt has been considered the hallmark of cpvt for many years .
however , recent studies1)2 ) have shown that ventricular bigeminy is the most common exercise - induced arrhythmia among patients with cpvt , and serious arrhythmias such as bidirectional vt and polymorphic vt are rarely induced .
therefore , exercise - induced ventricular bigeminy no longer should be considered an innocent arrhythmia , at least in suspicious cases of cpvt .
catecholaminergic polymorphic ventricular tachycardia may have both an autosomal dominant and an autosomal recessive pattern of inheritance .
the more common type 1 autosomal dominant cpvt is caused by mutations in ryr2 on chromosome 1q42-q42 and results from defective calcium release from the sarcoplasmic reticulum , which is required for myocardial contraction.3 ) a mutation in ryr2 can increase calcium release and cause life - threatening ventricular arrhythmias .
patients with ryr2 mutations become symptomatic at an early age , and men are at higher risk for cardiac events.4 ) in the autosomal recessive variant , type 2 cpvt , the causative gene is casq2 , located on chromosome 1p13 - 21.5 ) 
 casq2 encodes calsequestrin , a calcium buffering protein in the sarcoplasmic reticulum , which binds a large amount of calcium . while the mechanism by which this mutation causes ventricular arrhythmias
has not been clearly established , the mutated protein may be associated with the following : loss of polymerization of casq monomers , loss of calcium buffering capability , or indirect destabilization of the ryanodine receptor channel.6)7 ) patients with cpvt , in which many forms of exercise are associated with catecholamine release that triggers vt , should be cautioned against virtually all forms of vigorous and/or competitive physical activity.8 ) since the early reports on cpvt , -blockers have been used as primary therapy for cpvt,9)10 ) and they are indicated for both chronic treatment and acute therapy for sustained vt .
other antiarrhythmic drugs such as amiodarone and class i drugs have proved to be ineffective.11 ) however , these issues were addressed in a study that evaluated both the molecular mechanisms and clinical efficacy of flecainide in mice and humans.12 ) implantable cardioverter defibrillators can be considered for primary prevention despite the potential drawbacks in young patients and concerns about provoking arrhythmic storms . left cardiac sympathetic denervation has been reported effective in patients whose symptoms were not adequately controlled by -blockers.13 ) this approach may also be considered for individuals with intractable arrhythmic storms to reduce the number of implantable cardioverter - defibrillator shocks .
 a 16-year - old male with a prior history of recurrent syncope was referred to our hospital after being resuscitated from cardiac arrest developed while playing volleyball . 
 his electrocardiogram ( ecg ) demonstrated ventricular fibrillation at a local emergency department . 
 after referral , an ecg showed bidirectional ventricular tachycardia ( vt ) and nonsustained torsade de pointes . 
 two days later , his heart rate became regular , and no additional episodes of vt were observed . 
 his ecg showed sinus rhythm with a corrected qt interval of 423 msec , and two - dimensional echocardiography was unremarkable . 
 we made the diagnosis of a catecholaminergic polymorphic vt . 
 however , only premature ventricular complex bigeminy was induced on exercise ecg and epinephrine infusion tests , and the patient showed no episodes of syncope . 
 his father and mother had different missense mutations in the cardiac ryanodine receptor on genetic testing . 
 the proband had both mutations in different alleles and was symptomatic . 
 it was recommended that the patient avoid competitive physical activities , and a -blocker was prescribed . 
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