Epinephrine infusion in the evaluation of unexplained cardiac arrest and familial sudden death: from the cardiac arrest survivors with preserved Ejection Fraction Registry.

BACKGROUND Epinephrine infusion may unmask latent genetic conditions associated with cardiac arrest, including long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia (VT). METHODS AND RESULTS Patients with unexplained cardiac arrest (normal left ventricular function and QT interval) and selected family members from the Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER) registry underwent epinephrine challenge at doses of 0.05, 0.10, and 0.20 μg/kg per minute. A test was considered positive for long-QT syndrome if the absolute QT interval prolonged by ≥ 30 ms at 0.10 μg/kg per minute and borderline if QT prolongation was 1 to 29 ms. Catecholaminergic polymorphic VT was diagnosed if epinephrine provoked ≥ 3 beats of polymorphic or bidirectional VT and borderline if polymorphic couplets, premature ventricular contractions, or nonsustained monomorphic VT was induced. Epinephrine infusion was performed in 170 patients (age, 42 ± 16 years; 49% men), including 98 patients with unexplained cardiac arrest. Testing was positive for long-QT syndrome in 31 patients (18%) and borderline in 24 patients (14%). Exercise testing provoked an abnormal QT response in 42% of tested patients with a positive epinephrine response. Testing for catecholaminergic polymorphic VT was positive in 7% and borderline in 5%. Targeted genetic testing of abnormal patients was positive in 17% of long-QT syndrome patients and 13% of catecholaminergic polymorphic VT patients. CONCLUSIONS Epinephrine challenge provoked abnormalities in a substantial proportion of patients, most commonly a prolonged QT interval. Exercise and genetic testing replicated the diagnosis suggested by the epinephrine response in a small proportion of patients. Epinephrine infusion combined with exercise testing and targeted genetic testing is recommended in the workup of suspected familial sudden death syndromes. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032.