What is the clinical evidence from this study?

Study design: Observational. Population: Cardiomyopathy (n=172). Intervention: Medical therapy vs. None. Primary outcome: Left ventricular reverse remodeling (RR 2.0, 95% CI 1.75-2.27, p=0.002).

What does this research mean for the field?

TTN truncating variants are associated with a left ventricular reverse remodeling rate of 81.8%, while patients with LMNA variants show a 0% rate of remodeling. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

January 25, 2018Open Access

Genetic basis of cardiomyopathy and the genotypes involved in prognosis and left ventricular reverse remodeling

Key Result

TTN truncating variants were associated with a left ventricular reverse remodeling rate of 81.8% compared to 0% in patients with LMNA variants.

Study Design

Type

Observational (n=172)

Multicenter

Yes

Structured PICO

Does genotype (e.g., TTN vs LMNA variants) predict prognosis and left ventricular reverse remodeling in Japanese patients with dilated and hypertrophic cardiomyopathy?

Population

172 Japanese patients with cardiomyopathy, including 120 unrelated dilated cardiomyopathy (DCM) patients (mean age 39.1 years, 82.5% male, 41.7% familial) and 52 unrelated hypertrophic cardiomyopathy (HCM) patients (mean age 31.4 years, 61.5% male, 71.2% familial).

Intervention

Targeted sequencing of 95 genes associated with inherited cardiovascular diseases to identify pathogenic mutations and variants of uncertain significance.

Outcome

Composite outcome of death and heart transplantationhard clinical

In Japanese patients with dilated cardiomyopathy, TTN truncating variants are associated with a favorable prognosis and high rates of left ventricular reverse remodeling, whereas LMNA variants predict poor outcomes and lack of reverse remodeling.

Main Result

Effect estimate: RR 2.0 (95% CI 1.75-2.27)

Absolute Event Rate: 81.8% vs 0%

p-value: p=0.002

Limitations

Selection bias due to all participating institutions being advanced centers.
Retrospective analysis limits the ability to evaluate LVRR in all DCM patients.

Abstract

Abstract Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are genetically and phenotypically heterogeneous. Cardiac function is improved after treatment in some cardiomyopathy patients, but little is known about genetic predictors of long-term outcomes and myocardial recovery following medical treatment. To elucidate the genetic basis of cardiomyopathy in Japan and the genotypes involved in prognosis and left ventricular reverse remodeling (LVRR), we performed targeted sequencing on 120 DCM (70 sporadic and 50 familial) and 52 HCM (15 sporadic and 37 familial) patients and integrated their genotypes with clinical phenotypes. Among the 120 DCM patients, 20 (16.7%) had TTN truncating variants and 13 (10.8%) had LMNA variants. TTN truncating variants were the major cause of sporadic DCM (21.4% of sporadic cases) as with Caucasians, whereas LMNA variants, which include a novel recurrent LMNA E115M variant, were the most frequent in familial DCM (24.0% of familial cases) unlike Caucasians. Of the 52 HCM patients, MYH7 and MYBPC3 variants were the most common (12 (23.1%) had MYH7 variants and 11 (21.2%) had MYBPC3 variants) as with Caucasians. DCM patients harboring TTN truncating variants had better prognosis than those with LMNA variants. Most patients with TTN truncating variants achieved LVRR, unlike most patients with LMNA variants.

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