Cardiac Magnetic Resonance in a Patient with Pathogenic Mutations in Both Desmoplakin and Myosin-Binding Protein C (QF_TH_069)

A 38-year-old woman with no significant past medical history was referred for cardiology evaluation after she became tachycardic with ST changes on electrocardiogram during active labor. Transthoracic echocardiogram (TTE) revealed a left ventricular ejection fraction (LVEF) of 35%. Cardiac magnetic resonance (CMR) reported normal LV size with EF of 35%, with multifocal subendocardial and subepicardial myocardial scarring and 5% scar burden. CMR images were unavailable since it was performed at another hospital. She subsequently underwent genetic testing which identified pathogenic variants in the myosin-binding protein C (MYBPC3) and desmoplakin (DSP) genes. She was started on guideline directed medical therapy, with improvement in EF to 43% on TTE. Serial holter monitor did not reveal significant arrhythmias. She deferred primary prevention implantable defibrillator (ICD) placement. After several years of surveillance, she developed decreased exercise tolerance and was referred for a follow-up CMR for further evaluation.  

Diagnostic Techniques and Their Most Important Findings:

CMR with steady-state free precession (SSFP) cine imaging, T1 parametric mapping, and late gadolinium enhancement (LGE) imaging was performed. SSFP cine images demonstrated normal LV size with EF of 44%. There was diffuse mild hypocontractility, worse in the basal to mid anterolateral wall. The right ventricle was normal in size with normal systolic function and no regional wall motion abnormalities. Parametric mapping demonstrated elevated mean native T1 value signal (1200 ms), suggestive of diffuse myocardial fibrosis (Figure 1). LGE demonstrated diffuse subepicardial enhancement in the basal to mid LV segments (Figure 2).

Learning Points from this Case:

We present a case of a young patient with pathogenic mutations in both DSP and MYBPC3. DSP cardiomyopathy is a distinct form of arrhythmogenic cardiomyopathy (ACM) characterized by myocardial fibrosis that precedes systolic dysfunction and is associated with a high incidence of ventricular arrhythmias. The presence of any LV systolic dysfunction in DSP cardiomyopathy (LVEF < 55%), particularly when associated with LGE, indicates a substantial risk for severe ventricular arrhythmias. MYBPC3 gene is associated primarily with hypertrophic cardiomyopathy (HCM) but can also present as dilated cardiomyopathy. In patients with dilated cardiomyopathy, the MYBPC3 mutation is usually associated with absence of LGE in up to 50% of cases and with subepicardial LGE in only ~10% of cases. Patients with MYBPC3 mutation, similarly to DSP mutation, are at higher risk for ventricular arrhythmias if they manifest as HCM phenotype, and have systolic dysfunction (EF< 50%) or extensive LGE ( >=15%). In our case, CMR was more consistent with DSP mutation and no classic features of HCM were seen. The patient demonstrated high risk features for both mutations, including LV dysfunction and increased scar burden. Importantly, her scar burden had progressed compared to prior CMR. She subsequently underwent ICD placement and will continue ongoing surveillance for her cardiomyopathy. Our case highlights the importance of CMR in the surveillance of patients with gene mutations, as it helps to make genotype-phenotype correlations and clinical decisions such as the need for ICD implantation. In addition, CMR can assess for the progression of the fibrosis which can be seen in this distinct subtype of ACM.