Genotype influences end-stage heart failure occurrence in dilated cardiomyopathy

Abstract Introduction A monogenic cause of a dilated cardiomyopathy (DCM) phenotype is found in upto 37% of patients [1]. Purpose Evaluate the influence of genotype on end-stage heart failure (ESHF) outcomes in DCM. Methods Consecutive patients carrying variants from the 3 most prevalent DCM genotypes in a database from a cardiomyopathy unit (TTN, DSP and LMNA) and with features of DCM at baseline were retrospectively recruited. Consecutive DCM patients returning a negative result from a next generation DCM panel were recruited for comparison. ESHF was defined as left ventricular assist device implantation, heart transplantation or heart-failure related death. The incidence of ESHF was compared between genotypes during follow-up. Results 493 patients from 445 families (311 (63.1%) males, presenting at a median [IQR] age of 50.8 years [37.3 – 59.8]) with a median follow-up of 46.5 [28.1 – 88.2] months were recruited (Table 1). 26/493 (5.3%) of patients had ESHF by last evaluation. The highest incidence of ESHF was seen in LMNA variant-carriers and the lowest in genotype-negative patients (Figure 1). In a multivariable Cox model including age at presentation, sex and proband status, LMNA variant-carriage was associated with an increased risk of ESHF (HR 9.7 [4.6 – 20.6], p < 0.001) and genotype-negative status was associated with a reduced risk of ESHF (HR 0.08 [0.02 – 0.41], p = 0.002) Conclusions Genotype impacts the incidence of ESHF in patients with DCM. Close monitoring with early initiation of heart failure therapies is essential to mitigate this risk, particularly in LMNA variant-carriers.Table 1Figure 1