Idiopathic ventricular fibrillation: is it a case for genetic testing?

Area of Science:

• Cardiology
• Genetics
• Sudden Cardiac Arrest Research

Background:

• Idiopathic ventricular fibrillation (IVF) is a diagnosis of exclusion in sudden cardiac arrest (SCA) survivors.
• Less than 20% of SCA survivors receive a complete work-up, leading to potential misdiagnosis of IVF.
• 10-20% of SCA survivors have an undiagnosed inherited cardiac condition (ICC).

Purpose of the Study:

• To evaluate the role and timing of genetic testing in SCA survivors.
• To determine the diagnostic yield of genetic testing in relation to panel size and phenotype.
• To discuss the implications of ICC diagnosis for patients and their families.

Main Methods:

• Review of clinical work-up guidelines for SCA survivors.
• Analysis of diagnostic yield of genetic testing with varying gene panel sizes.
• Discussion of the role of deep phenotyping and segregation analysis.

Main Results:

• Genetic testing is crucial as 10-20% of presumed IVF patients have an ICC.
• Larger gene panels do not increase diagnostic yield but increase variants of unknown significance (VUS).
• Multidisciplinary team approach is vital for VUS interpretation through segregation analysis.

Conclusions:

• Routine genetic testing in SCA survivors is debated but recommended.
• Combining deep phenotyping with genetic testing is preferable, especially in younger individuals.
• Accurate diagnosis of ICC impacts patient and family treatment and management.