Characteristics of VCP mutation-associated cardiomyopathy

Area of Science:

• Cardiology
• Genetics
• Neurology

Background:

• VCP associated inclusion body myopathy, Paget's disease of bone, and Frontotemporal Dementia (IBMPFD) is an autosomal dominant disorder caused by VCP gene mutations.
• Cardiovascular complications are common in advanced stages of IBMPFD.
• Early detection of cardiac involvement is crucial for managing VCP disease.

Purpose of the Study:

• To investigate echocardiographic features in asymptomatic carriers and affected individuals with VCP mutations.
• To identify potential early indicators of VCP-associated cardiomyopathy.
• To compare cardiac function between symptomatic patients and asymptomatic carriers.

Main Methods:

• Observational cross-sectional study of 32 patients with VCP mutations (23 affected, 9 asymptomatic carriers).
• Echocardiographic assessment of cardiac function.
• Longitudinal follow-up of a subset of affected individuals.

Main Results:

• Diastolic dysfunction was present in 43.5% of symptomatic VCP disease patients, but not in asymptomatic carriers (p=0.017).
• Asymptomatic carriers were significantly younger than affected individuals (38.4 vs 50.6 years, p<0.001).
• Among 5 affected individuals followed longitudinally, 3 developed diastolic dysfunction, and 2 already had it.

Conclusions:

• Diastolic dysfunction appears to be an early echocardiographic feature in VCP disease.
• Asymptomatic carriers of VCP mutations may not exhibit early cardiac dysfunction.
• Further research with advanced imaging modalities is warranted to fully characterize cardiac involvement in VCP disease.