A 17-year-old previously healthy Caucasian female presents with a recent history of syncope while rowing in open water. She fainted and fell out of her boat. She reports that she usually rows on a 4- to 8-person boat, but on the day she fainted, she was rowing by herself and harder than usual. It was early morning, and she did not eat breakfast or drink anything before rowing. She felt a brief “flutter” in her chest and woke up under water and does not remember how she got there. The patient does not report any inter-current illnesses or prior history of fainting. There is no family history of syncope or sudden death. During her assessment in the local hospital emergency room, her vital signs are within normal limits. Her electrocardiogram (EKG) and echocardiogram are normal. Discussion: Syncope and near-syncope can be diagnostic challenges as they may result from a benign or a life-threatening condition. Exercise-induced syncope, as in this case, is almost always associated with a serious underlying cardiac condition. The cardiac causes of exercise-induced syncope include 1) arrhythmogenic right ventricular cardiomyopathy, 2) hypertrophic cardiomyopathy, 3) coronary artery anomalies, 4) aortic stenosis, 5) long QT syndrome, 6) catecholamine-sensitive polymorphic ventricular tachycardia, 7) profound bradycardia or asystole, 8) pulmonary hypertension, and rarely, 9) myocarditis.
Our patient was diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC) after a complete diagnostic work up.
An EKG showed normal sinus rhythm with normal QTc measurements, but also had abnormal T-wave inversion in the precordial leads V1-V5 (see Figure 1). T-wave inversion in the right precordial leads (V1, V2 and V3) is considered a benign juvenile repolarization pattern in young patients, but when present in individuals >14 years of age should raise the possibility of ARVC, especially when accompanied by cardiac symptoms.
A Holter monitor revealed nonsustained monomorphic ventricular tachycardia (VT) while the patient was exercising on a stationary rowing machine in the gym (see Figure 2). An exercise stress test demonstrated salvos of nonsustained monomorphic VT (see Figure 3). The patient’s echocardiogram and cardiac MRI were normal.
A 15-lead EKG shows normal sinus rhythm, normal intervals, and normal voltages. There is a right superiorly directed QRS axis. There is minimal right ventricular conduction delay. Note abnormal T-wave inversion in lead V1-V5.
A 24-hour Holter showed a run of nonsustained ventricular ventricular tachycardia with exercise. The closest R-R interval was 220 msec.
An exercise stress test shows a ventricular couplet followed by nonsustained monomorphic VT with a LBBB morphology. Note negative QRS complexes in lead V1 in the ventricular couplet and positive QRS complexes in V6 during VT during exercise.
An electrophysiology study was performed and, with isoproterenol infusion there was an inducible monomorphic VT with a left bundle branch block (LBBB) morphology and inferior axis correlating with a site of origin in the RV outflow tract (see Figure 4). Genetic testing for ARVC revealed a deleterious frameshift mutation PKP2Thr50FS in the plakophilin-2 gene, which is associated with ARVC.
ARVC is an inherited cardiomyopathy characterized by frequent ventricular arrhythmias, progressive predominant RV dysfunction, and sudden cardiac death (SCD). Up to two-thirds of ARVC patients have mutations in genes encoding the cardiac desmosome. Mechanical stress has been shown to exaggerate desmosomal dysfunction, which may be one explanation for the frequent finding of ARVC disease in athletes.
The clinician should consider ARVC in adolescents or young individuals with frequent premature ventricular contractions (PVCs), VT, suspected cardiac syncope, or aborted cardiac arrest. VT with LBBB morphology is the most common morphology associated with ARVC. There is no single, gold-standard diagnostic test, and the diagnosis relies on a scoring system with “major” and “minor” criteria based on a combination of defects in 6 categories, including EKG repolarization or depolarization abnormalities, ventricular arrhythmias,morphological and functional RV changes, plus histopathology, family history, and genetic findings. As per the recent Task Force criteria, the diagnosis is fulfilled by the presence of 2 major or 1 major plus 2 minor criteria or 4 minor criteria.
In the “concealed” phase of the disease, the diagnosis may be challenging, as in this case. The combination of an abnormal EKG (T-wave inversion in precordial leads), inducible VT with exercise, and inducible VT with provocative electrophysiology testing, suggesting a
site of VT origin in the RV, were strongly suspicious for ARVC. In early stages, echocardiogram and cardiac MRI can be normal. Disease-specific genetic testing revealed a deleterious plakophilin-2 mutation, which accounts for 20 to 40% of ARVC. Family testing revealed that the patient’s asymptomatic father carried this mutation.
Inducible monomorphic VT (rate 280 bpm) with LBBB morphology and inferior frontal QRS axis.
Preventing SCD is the most important management task for patients affected by ARVC. Treatment options include an implantable cardioverter defibrillator (ICD) for prevention of SCD. Pharmacologic treatment with beta blockers and amiodarone as well as radiofrequency ablation (RFA) are considered adjunct therapy for ventricular arrhythmias, and they are not an equivalent alternative to ICD therapy in high-risk patients. Additionally, lifestyle modifications, including avoiding competitive sports, are necessary to reduce phenotypic expression and arrhythmia.
In our patient, the VT focus was successfully ablated with RFA, and an ICD was implanted for prevention of SCD. The patient was counselled to avoid competitive sports. She has been symptom-free, arrhythmia-free for 24 months.