A 5-year-old girl presented to her pediatrician's office for a routine well-child visit. She was asymptomatic and developmentally normal. Parents reported that she participated in all activities but was not as active as her siblings. She was taking no medications. She had never been hospitalized or undergone surgery. Her examination was notable only for bradycardia with a heart rate (HR) of 52 beats per minute (bpm). She had normal weight, height, and blood pressure, with no evidence of thyromegaly. Both parents were healthy, as were the girl's older sister and younger brother. There was no family history of congenital heart disease, seizures, syncope, early sudden death, or family members requiring pacemakers or defibrillators.
The patient's ECG showed sinus rhythm at 50–60
bpm with normal PR, QRS, and corrected QT (QTc) intervals (). Due to the bradycardia, a Holter monitor was performed to evaluate her HR variability. The monitor showed sinus bradycardia with an average HR of 59
bpm and a minimum of 37
BPM. There was no atrioventricular (AV) conduction delay, and repolarization appeared normal. At rates greater than 110–120
bpm, there were frequent polymorphic premature ventricular contractions (PVCs) and bigeminy with runs of nonsustained bidirectional ventricular tachycardia (VT) at 211
BPM, suspicious for a clinical diagnosis of CPVT. Additionally, brief runs of a supraventricular tachycardia (SVT) at a rate of 220
bpm were also noted (). The parents reported that their daughter was active at these times and free of any symptoms.
Figure 1 Baseline ECG showing sinus rhythm at 50–60bpm with normal PR, QRS, and QTc intervals.
Rhythm strip from Holter monitor showing bidirectional VT, wide QRS complex tachycardia with alternating QRS axis (arrows), followed by nonsustained SVT, narrow QRS complex tachycardia (asterisks), then spontaneous termination to sinus rhythm (SR).
An echocardiogram performed to assess cardiac anatomy and function revealed an overall normal appearing heart with normal LV chamber size and systolic function, but with heavy trabeculations in the LV apex, suggestive of LVNC. Cardiac magnetic resonance imaging showed similar noncompacted myocardium in the LV apex with normal LV chamber size and function and no other abnormalities. Initial laboratory testing including basic metabolic profile, inflammatory markers, complete blood count, and liver and thyroid function tests were within normal limits. The patient underwent an exercise treadmill test (ETT) to assess for inducible arrhythmias in a controlled setting. She had sinus rhythm at 55–70
bpm at rest and developed polymorphic PVCs and bigeminy at HRs greater than 110
bpm (). The ETT was terminated at 7 minutes (min) due to the complex ventricular ectopy, although the girl had no symptoms. The PVCs dissipated by 1
min of recovery, as her HR dropped below 100
Exercise Treadmill Test. (a) Peak-exercise ECG on initial ETT, prior to antiarrhythmic medications, showing polymorphic PVCs and bigeminy (arrows). (b) Peak-exercise ECG on ETT during esmolol infusion, showing sinus rhythm with suppression of PVCs.
Beta-blocker therapy was initially considered to prevent the tachyarrhythmias, but due to her profound baseline bradycardia, a class 1C sodium channel blocker antiarrhythmic medication (flecainide) was started. A repeat ETT showed no reduction of PVCs during exercise. Therefore, the flecainide was discontinued and a beta-blocker trial was started with esmolol (infusion rate of 250
mcg/kg/min). This short-acting intravenous (IV) beta-blocker was chosen, so that the medication could be discontinued immediately if her basleine bradycardia was exacerbated or the beta-blocker resulted in hemodynamic compromise. A repeat ETT showed resting sinus rates of 50–60
bpm and a peak HR of 118 bpm at 9.5
min of exercise. Rare PVCs were noted with exercise and suppressed completely at peak HRs (). Due to potential exacerbation of her underlying bradycardia with beta-blocker therapy, a dual chamber epicardial pacemaker was implanted, and she was started on a long-acting oral β
-blocker, nadolol (1.0
mg/kg/day). Immediately postoperatively, she had intermittent PVCs and mild hypertension that resolved by increasing nadolol to 2.0
mg/kg/day. Prior to pacemaker implantation, there was a lengthy discussion regarding her arrhythmia substrate and possible implantable cardioverter defibrillator (ICD) placement for primary prevention. Since our patient had no history of syncope and appeared to have an excellent response to beta-blockade, the decision was made against ICD implantation for primary prevention.
Repeat ETT, performed 6 weeks after pacemaker implantation, showed a resting sinus rate of 70
bpm and peak HR of 117
bpm at 10
min of exercise. Rare single monomorphic PVCs noted with exercise suppressed completely at peak HRs. She reported mild fatigue during daily activities, and her pacemaker was reprogrammed on for rate response to allow more physiology heart rate with daily activities. At her 5-month followup she had improvement in her fatigue and no palpitations or syncope. She continued on nadolol with exercise restrictions. Her Holter monitor showed sinus alternating with atrial pacing with good beta-blockade effect and no ventricular arrhythmias. Her echocardiogram was unchanged.
Candidate gene testing was performed due to her history of arrhythmias. A long QT syndrome panel revealed no disease-causing mutations. A pan cardiomyopathy microarray designed to identify mutations in genes associated with cardiomyopathy and CPVT revealed three mutations: ryanodine receptor (RyR2) Arg169Gln, calsequestron (CASQ2) Asp398del, and titin (TTN) Lys4455Arg. These were all single nucleotide changes resulting in missense mutations.