Phenotype and Outcomes of Titin Cardiomyopathy

Study Questions:

What are the relationships between sarcomeric protein titin (TTNtv) genotype, cardiac phenotype, and outcomes in dilated cardiomyopathy (DCM) when compared to DCM without TTNtv?


This was a prospective, observational cohort study in which DCM patients underwent clinical evaluation, late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR), TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events. The primary analysis was to evaluate association of TTNtv with the primary endpoint on univariable and multivariable analysis.


The final study population consisted of 716 patients (mean age [± standard deviation] 53.5 ± 14.3 years, 469 men [65.5%]), with a clinical and imaging diagnosis of DCM confirmed by CMR. The majority of patients were in New York Heart Association (NYHA) class I (n = 300, 41.9%) or II (n = 277, 38.7%) at enrollment, reflecting the ambulatory status of the patients in this cohort. Of 716 subjects enrolled, 577 (80.6%) were in NYHA class I/II, and 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 vs. 54.1 years, p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction, padjusted = 0.03) compared to patients without TTNtv. The study investigators found no difference in biventricular ejection fraction between TTNtv ± groups. Overall, 12.9% (78 of 604) of patients met the primary endpoint (median follow-up 3.9 years, interquartile range 2.0-5.8), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events for patients with or without TTNtv (adjusted HR for primary endpoint, 0.92; 95% confidence interval, 0.45-1.87; p = 0.8). The results from the unadjusted and adjusted HR for TTNtv on the primary endpoint were very similar (unadjusted HR, 0.85; p = 0.64; adjusted HR, 0.92; p = 0.8).


The authors concluded that TTNtv DCM does not appear to be associated with worse medium-term prognosis.


This is an important study because the study cohort was large. The next step would be to conduct large multicenter studies to confirm the findings of this study.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Magnetic Resonance Imaging

Keywords: Arrhythmias, Cardiac, Cardiomyopathy, Dilated, Cardiomyopathies, Connectin, Diagnostic Imaging, Gadolinium, Genotype, Heart Failure, Magnetic Resonance Imaging, Phenotype, Sarcomeres, Stroke Volume

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