Dilated cardiomyopathy and arrhythmogenic left ventricular cardiomyopathy: a comprehensive genotype-imaging phenotype study

Aims: Myocardial scar detected by cardiovascular magnetic resonance has been associated with sudden cardiac death in dilated cardiomyopathy (DCM). Certain genetic causes of DCM may cause a malignant arrhythmogenic phenotype. The concepts of arrhythmogenic left ventricular (LV) cardiomyopathy (ALVC) and arrhythmogenic DCM are currently ill-defined. We hypothesized that a distinctive imaging phenotype defines ALVC. Methods and Results: Eighty-nine patients with DCM-associated mutations [desmoplakin (DSP) n = 25, filamin C (FLNC) n= 7, titin n= 30, lamin A/C n = 12, bcl2-associated athanogene 3 n = 3, RNA binding motif protein 20 n= 3, cardiac sodium channel NA(v)1.5 n= 2, and sarcomeric genes n = 7] were comprehensively phenotyped. Clustering analysis resulted in two groups: `DSP/FLNC genotypes' and `non-DSP/FLNC'. There were no significant differences in age, sex, symptoms, baseline electrocardiography, arrhythmia burden, or ventricular volumes between the two groups. Subepicardial LV late gadolinium enhancement with ring-like pattern (at least three contiguous segments in the same short-axis slice) was observed in 78.1% of DSP/FLNC genotypes but was absent in the other DCM genotypes (P < 0.001). Left ventricular ejection fraction (LVEF) and global longitudinal strain were lower in other DCM genotypes (P=0.053 and P= 0.015, respectively), but LV regional wall motion abnormalities were more common in DSP/FLNC genotypes (P < 0.001). DSP/FLNC patients with non-sustained ventricular tachycardia (NSVT) had more LV scar (P=0.010), whereas other DCM genotypes patients with NSVT had lower LVEF (P= 0.001) than patients without NSVT. Conclusions: DSP/FLNC genotypes cause more regionality in LV impairment. The most defining characteristic is a subepicardial ring-like scar pattern in DSP/FLNC, which should be considered in future diagnostic criteria for ALVC.