Inferior and anterior QRS fragmentation have different prognostic value in patients who received an implantable defibrillator in primary prevention of sudden cardiac death.

AIMS: QRS fragmentation (fQRS) has been proposed as a predictor of sudden cardiac death (SCD) and all-cause mortality in ischemic (ICM) and non-ischemic cardiomyopathy patients. However the value of fQRS in patients with a LVEF <35% is a matter of debate. METHODS: All consecutive patients with an indication for an ICD in primary prevention of SCD were included in a retrospective registry from 1996 until 2013. Twelve lead electrocardiograms before implant were analyzed for the presence of fQRS in different regions. Adjusted Cox regression analysis for first appropriate ICD shock (AS) and all-cause mortality was performed. RESULTS: In total 407 patients were included with a mean follow-up of 4.2±3.3y (age 60.6±11.9y, 15.7% female and 52.8% ICM). fQRS was present in 46.7% of patients, predominantly inferior (30.7%) followed by anterior (21.4%) and lateral (11.1%) coronary artery territories. fQRS was significantly more prevalent in ICM (p=0.004). Inferior fQRS was an independent predictor of a first AS within 1y (HR 2.55, 95%CI 1.28-5.07) and 3y (HR 1.90, 95%CI 1.14-3.18) after implantation. Whereas, anterior fQRS was an independent predictor of all-cause mortality within 1y (HR 4.58, 95%CI 1.29-16.19), 3y (HR 3.92, 95%CI 1.77-8.65) and the complete follow-up (HR 2.22, 95%CI 1.33-3.69). Lateral fQRS was only a predictor of late (>3y of follow-up) all-cause mortality (HR 2.04, 95%CI 1.09-3.81). CONCLUSIONS: fQRS in a specific coronary artery territory might be promising to discriminate arrhythmic from mortality risk. Inferior fQRS was a predictor of early arrhythmia, while anterior fQRS was related to mortality.

Reduced Penetrance and Variable Expression of SCN5A Mutations and the Importance of Co-inherited Genetic Variants: Case Report and Review of the Literature.

Mutations in the SCN5A gene are responsible for multiple phenotypical presentations including Brugada syndrome, long QT syndrome, progressive familial heart block, sick sinus syndrome, dilated cardiomyopathy, lone atrial fibrillation and multiple overlap syndromes. These different phenotypic expressions of a mutation in a single gene can be explained by variable expression and reduced penetrance. One of the possible explanations of these phenomena is the co-inheritance of genetic variants. We describe a family where the individuals exhibit a compound heterozygosity in the SCN5A gene including a mutation (R1632H) and a new variant (M858L). Individuals with both the mutation and new variant present with a more severe phenotype including spontaneous atrial tachyarrhythmia at young age. We give an overview of the different phenotypes of "SCN5A disease" and discuss the importance of co-inherited genetic variants in the expression of SCN5A disease.