Posts Tagged ‘genetic testing’

Genetic Testing in Unexplained Cardiac Arrest

Mellor et al (Circ Cardiovasc Genet. 2017;10:e001686. DOI: 10.1161/CIRCGENETICS.116.001686.) provide a very instructive paper on the value of genetic testing in evaluation of unexplained cardiac arrest. A significant proportion of survivors had a pathogenic variant identified.



Unexplained cardiac arrest may be because of an inherited arrhythmia syndrome. The role of genetic testing
in cardiac arrest survivors without a definite clinical phenotype is unclear.

Methods and Results

The CASPER (Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) is a large
registry of cardiac arrest survivors where initial assessment reveals normal coronary arteries, left ventricular function,
and resting ECG. Of 375 cardiac arrest survivors in CASPER from 2006 to 2015, 174 underwent genetic testing. Patients
were classified as phenotype-positive (n=72) or phenotype-negative (n=102). Genetic testing was performed at treating
physicians’ discretion in line with contemporary guidelines and availability. All genetic variants identified from original
laboratory reports were reassessed by the investigators in line with modern criteria. Pathogenic variants were identified
in 29 (17%) patients (60% channelopathy-associated and 40% cardiomyopathy-associated genes) and 70 variants of
unknown significance were identified in 32 (18%) patients. Prior syncope (odds ratio, 4.0; 95% confidence interval,
1.6–9.7) and a family history of sudden death (odds ratio, 3.2; 95% confidence interval, 1.1–9.4) were independently
associated with the presence of a pathogenic variant. In phenotype-negative patients, broad multiphenotype genetic
testing led to higher yields (21% versus 8%; P=0.04) but was associated with more variants of unknown significance
(55% versus 5%; P<0.01).


Genetic testing identifies a pathogenic variant in a significant proportion of unexplained cardiac arrest
survivors. Prior syncope and family history of sudden death are predictors of a positive genetic test. Both arrhythmia
and cardiomyopathy genes are implicated. Broad, multiphenotype testing revealed the highest frequency of pathogenic
variants in phenotype-negative patients.