What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Arrhythmogenic right ventricular cardiomyopathy (ARVC) (n=1113). Intervention: Presence of desmosomal gene mutations vs. Absence of desmosomal gene mutations. Primary outcome: T wave inversion in V1-3 leads (p=0.0002).

January 25, 2017Open Access

Genotype-phenotype relationship in patients with arrhythmogenic right ventricular cardiomyopathy caused by desmosomal gene mutations: A systematic review and meta-analysis

Key Result

The presence of desmosomal gene mutations in ARVC patients was associated with a younger onset age (32.7 vs 43.2 years) and a higher incidence of T wave inversion in V1-3 leads (78.5% vs 51.6%).

Study Design

Type

Meta-Analysis (n=1,113)

Structured PICO

Does the presence of desmosomal gene mutations affect clinical phenotypes in patients with ARVC?

Population

11 studies involving 1,113 unrelated and consecutive patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) where at least 2 desmosomal genes were sequenced.

Intervention

Presence of desmosomal gene mutations

Comparator

Absence of desmosomal gene mutations (desmosomal-negative)

Outcome

Clinical features including onset age of ARVC, gender, and phenotypic features on the basis of international task force criteria (TFC): global or regional dysfunction and structural alterations, T wave inversion in right precordial leads (V1-3), epsilon wave in right precordial leads (V1-3), ventricular tachycardia of left bundle-branch morphology, and family history of ARVC

In patients with ARVC, the presence of desmosomal gene mutations is associated with an earlier onset age, a higher incidence of T wave inversion in V1-3 leads, and a strong family history of the disease.

Main Result

Absolute Event Rate: 78.5% vs 51.6%

p-value: p=0.0002

Limitations

Substantial differences regarding study design, case ascertainment and the assessment of clinical manifestations.
Several factors might influence disease expression, such as mutations unique to each family, ethnic background, and environmental factors.
Inconsistent diagnosis criteria of ARVC across studies.
Meta-analysis of specific associations between individual desmosomal gene mutations and clinical phenotypes was not possible due to limited data.

Abstract

Abstract The relationship between clinical phenotypes and desmosomal gene mutations in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is poorly characterized. Therefore, we performed a meta-analysis to explore the genotype-phenotype relationship in patients with ARVC. Any studies reporting this genotype-phenotype relationship were included. In total, 11 studies involving 1,113 patients were included. The presence of desmosomal gene mutations was associated with a younger onset age of ARVC (32.7 ± 15.2 versus 43.2 ± 13.3 years; P = 0.001), a higher incidence of T wave inversion in V 1–3 leads (78.5% versus 51.6%; P = 0.0002) or a family history of ARVC (39.5% versus 27.1%; P = 0.03). There was no difference in the proportion of males between desmosomal-positive and desmosomal-negative patients (68.3% versus 68.9%; P = 0.60). The presence of desmosomal gene mutations was not associated with global or regional structural and functional alterations (63.5% versus 60.5%; P = 0.37), epsilon wave (29.4% versus 26.2%; P = 0.51) or ventricular tachycardia of left bundle-branch morphology (62.6% versus 57.2%; P = 0.30). Overall, patients with desmosomal gene mutations are characterized by an earlier onset age, a higher incidence of T wave inversion in V 1–3 leads and a strong family history of ARVC.

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