Isolated Progressive Cardiac Conduction Disease

Isolated progressive cardiac conduction disease (PCCD) refers to a group of genetic disorders that involve progressively worsening defects in cardiac conduction, including sinus node dysfunction, varying degrees of atrioventricular (AV) block and/or His-Purkinje system conduction delays or blocks.

PCCD may be

• Structural: Accompanied or followed by structural heart disease (eg, congenital heart disease, cardiomyopathy)

• Isolated: Occurring in a structurally normal heart

The most common form of PCCD associated with a cardiomyopathy is one in which mutations in LMNA are present (see Lamin A/C Cardiomyopathy. Some such patients present with an apparently structurally normal heart but subsequently develop cardiomyopathy.

Isolated PCCD patients typically present with early-onset (age < 50 years), progressive conduction system disease manifest as one or more of the following:

• Sinus node dysfunction

• Slowed intra-atrial conduction

• AV node disease

• His-Purkinje system disease (ie, bundle branch blocks or fascicular blocks)

A degenerative form, in which the conducting system becomes sclerotic, has been referred to as Lenègre-Lev disease.

Isolated PCCD results predominantly from mutations in SCN5A, the gene that encodes the Nav1.5 channel responsible for the inward sodium (INa) current. Inheritance is typically in an autosomal dominant pattern. Overlap syndromes with the long QT syndrome and with Brugada syndrome have been reported.

The disorder is manifest by ECG changes including prolonged PR interval, widened P wave, widened QRS complex, AV block, right bundle branch block, left anterior hemiblock, left posterior hemiblock, left bundle branch block, or nonspecific interventricular conduction block. Patients also have a higher risk of sudden death.

Patients should have cardiac imaging (eg, echocardiography, MRI) to detect any structural disorders. Patients without structural disease should have genetic testing, particularly if they have a family history of sudden cardiac death or of need for pacemaker implantation at a young age. If testing reveals a genetic abnormality, family members should be screened with ECG and genetic testing.

Treatment is with a pacemaker following the usual indications for pacemaker implantation, including third-degree AV block or symptomatic second-degree AV block. A consensus recommendation is that pacemakers may also be useful in patients with familial isolated PCCD who have bifasicular block with or without first-degree AV block (1).