Frameshifts in Code and in Care: The Importance of Timely Genetic Evaluation.

Abstract

In the coming years, remarkable advances in understanding the genetic underpinnings of rare and common disorders will transform the clinical care of patients with inherited cardiovascular conditions. Discoveries from genome-wide association studies, next-generation sequencing studies, and novel bioinformatics approaches have already revolutionized our diagnostic capabilities for monogenic and polygenic disorders. Translating and implementing this information into daily clinical practice lags considerably. We are confronting a significant genetics/genomics literacy gap in the clinical workforce that threatens to widen without dedicated efforts to address it. Here, we present a case that highlights the importance of a soliciting a minimum 3-generation family history in all cases of cardiomyopathy and the pitfalls of ordering genetic testing without a sufficient infrastructure for interpretation and return of results. A 58-year-old woman was referred to our institution for management of recurrent atrial and ventricular arrhythmias. She first experienced palpitations at age 14 years, which were initially attributed to atrial arrhythmias and were well controlled on medical therapy. In her early 40s, they became refractory to antiarrhythmic medications. She underwent multiple electrical cardioversions and catheter ablations for atrial flutter, atrial fibrillation, and atrial tachycardia with a decrease in atrial arrhythmia burden but incomplete control. At age of 50 years, a dual chamber pacemaker was implanted for sinus node dysfunction. On routine device interrogation 19 months later, she was noted to have recurrent nonsustained ventricular tachycardia (VT) and was referred for cardiac magnetic resonance imaging (MRI) to evaluate for left ventricular (LV) and right ventricular fibrosis. Cardiac MRI demonstrated extensive multifocal patchy midmyocardial delayed gadolinium enhancement thought to be consistent with myocarditis versus cardiac sarcoidosis. Her moderately decreased LV ejection fraction of 43% was attributed to poor ventricular rate control with recurrent atrial arrhythmias. Subsequent evaluation with F-18 fluorodeoxyglucose (18F-FDG) cardiac positron emission tomography/computed tomography (PET/CT) showed no …