Dilated cardiomyopathy caused by truncating titin variants: long-term outcomes, arrhythmias, response to treatment and sex differences

Christoffer Rasmus Vissing, Torsten Bloch Rasmussen, Anne Mette Dybro, Morten Salling Olesen, Lisbeth Nørum Pedersen, Morten Jensen, Henning Bundgaard, Alex Hørby Christensen

9 Citations (Scopus)


BACKGROUND: Truncating variants in titin (TTNtv) are the most common cause of dilated cardiomyopathy (DCM). We evaluated the genotype-phenotype correlation in TTNtv-DCM, with a special focus on long-term outcomes, arrhythmias, response to treatment and sex-related presentation.

METHODS: Data on patient characteristics and outcomes were collected retrospectively from electronic health records of patients genotyped at two Danish heart transplantation centres.

RESULTS: We included 115 patients (66% men). At diagnosis of DCM, mean age was 46±13 years and left ventricular ejection fraction (LVEF) was 28%±13%. During a median follow-up of 7.9 years, 26% reached a composite outcome of left ventricular assist device implantation, heart transplantation or death. In 20% an arrhythmia preceded the DCM diagnosis. In total, 43% had atrial fibrillation (AF) and 23% had ventricular arrhythmias. Long-term left ventricular reverse remodelling (LVRR; LVEF increase ≥10% points or normalisation) was achieved in 58% and occurred more frequently in women (72% vs 51%, p=0.042).In multivariable proportional hazards analyses, occurrence of LVRR was a strong independent negative predictor of the composite outcome (HR: 0.05 (95% CI 0.02 to 0.14); p<0.001). Female sex independently predicted lower rates of ventricular arrhythmias (HR: 0.33 (95% CI 0.11 to 0.99); p=0.05), while the location of the TTNtv was not associated with cardiovascular outcomes.

CONCLUSION: DCM caused by TTNtv presented in midlife and was associated with a high burden of AF and ventricular arrhythmias, which often preceded DCM diagnosis. Furthermore, LVRR occurred in a high proportion of patients and was a strong negative predictor of the composite outcome. Female sex was positively associated with occurrence of LVRR and longer event-free survival.

Original languageEnglish
Article number107178
JournalJournal of Medical Genetics
Issue number12
Pages (from-to)832-841
Number of pages10
Publication statusPublished - Dec 2021


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