Hot Hot Hot- Desmoplakin Mutation Induced Fibrofatty Replacement of the Left Ventricle in Arrhythmogenic Cardiomyopathy

Description of Clinical Presentation: 58 year old male with a medical history significant for non-obstructive coronary artery disease, hypertension, and obesity presenting with chest discomfort found to have an elevated troponin and new cardiomyopathy with left ventricular ejection fraction of 35-40%. Home medications include aspirin and atorvastatin. He is a never smoker and only drinks alcohol socially. Family history is noncontributory.

Diagnostic Techniques and Their Most Important Findings: Axial imaging with balanced steady state images and cine imaging in multiple cardiac specific orientations were obtained. Following these sequences, post contrast images with inversion recovery as well as T1 and T2 mapping were performed.

Regions of fatty replacement were observed throughout aspects of the left ventricle as well as bite-like fibrofatty replacement of the apical lateral segment. Left ventricular systolic function was moderately reduced with regional wall motion changes. The left ventricle was normal in size with regional thinning. There was evidence of elevated myocardial T2 times on parametric mapping, suggestive of myocardial edema.

Right ventricular systolic function was normal with apparent fibrofatty replacement in the
basal lateral free wall and associated regional akinesia. The right ventricle was noted to be small in size.

Cardiac MRI findings were highly suggestive of a left dominant arrhythmogenic cardiomyopathy phenotype. Taken concomitantly with the evidence of elevated T2 parametric mapping to suggest the presence of myocardial edema – concern for the “Hot phase” of arrhythmogenic cardiomyopathy was also raised.

Learning Points from this Case: The “Hot phases” of cardiomyopathy is a newly emerging clinical entity that spans a wide overlap of clinical syndromes including myocarditis, arrhythmogenic cardiomyopathy, and dilated cardiomyopathies which may be characterized by repetitive episodes of inflammation. These “Hot phases” are theorized to exacerbate arrhythmic risk and may contribute to disease progression. (citation below)

Desmoplakin and filamin-C mutations are more commonly associated with arrhythmogenic phenotype of left dominant arrhythmogenic cardiomyopathy (LDAC). LDAC may manifest as left ventricular (LV) dilation/systolic dysfunction with regional wall motion abnormalities, fibrosis or fibrofatty replacement. The specific finding of a focal “bite like” fatty infiltration in subepicardial apical lateral LV has been described within the literature to be highly suggestive. Of note, this finding is observed in every third arrhythmogenic right ventricular cardiomyopathy (ARVC) patient and is seen in a significant number of family members of an ARVC proband.

Ultimately our patient underwent dual chamber ICD placement given non ischemic and arrhythmogenic cardiomyopathy with biventricular involvement. Subsequent genetic testing revealed a pathogenic variant in the desmoplakin (DSP) gene ultimately confirming the de novo diagnosis of left dominant arrhythmogenic cardiomyopathy phenotype.

Steady State Free Precession sequence showing bite-like fibrofatty replacement of the apical lateral segment in the four chamber orientation.
T2 parametric mapping showed evidence of elevated times in the basal to mid anteroseptal, anterior, and mid inferolateral segments.
Delayed enhancement sequences showing extensive late gadolinium enhancement (LGE) including linear subepicardial LGE of the basal to mid anterior and basal inferolateral walls with dense subepicardial to mid myocardial LGE of the basal anteroseptal and basal to mid inferoseptal and inferior walls. Additionally, there is focal subepicardial to mid myocardial LGE of the apical lateral segment.