Systemic diseases can cause heart block owing to the involvement of the myocardium and thereby the conduction system. Younger patients (<60) with heart block should be evaluated for an underlying systemic disease. These disorders are classified into infiltrative, rheumatologic, endocrine, and hereditary neuromuscular degenerative diseases. Cardiac amyloidosis owing to amyloid fibrils and cardiac sarcoidosis owing to noncaseating granulomas can infiltrate the conduction system leading to heart block. Accelerated atherosclerosis, vasculitis, myocarditis, and interstitial inflammation contribute to heart block in rheumatologic disorders. Myotonic, Becker, and Duchenne muscular dystrophies are neuromuscular diseases involving the myocardium skeletal muscles and can cause heart block.

Atrioventricular blocks may be caused by a variety of potentially reversible conditions, such as ischemic heart disease, electrolyte imbalances, medications, and infectious diseases. Such causes must be always ruled out to avoid unnecessary pacemaker implantation. Patient management and reversibility rates depend on the underlying cause. Careful patient history taking, monitoring of vital signs, electrocardiogram, and arterial blood gas analysis are crucial elements of the diagnostic workflow during the acute phase. Atrioventricular block recurrence after the reversal of the underlying cause may pose an indication for pacemaker implantation, because reversible conditions may actually unmask a preexistent conduction disorder.

Iatrogenic atrioventricular (AV) block can occur in the context of cardiac surgery, percutaneous transcatheter, or electrophysiologic procedures. In cardiac surgery, patients undergoing aortic and/or mitral valve surgery are at the highest risk for developing perioperative AV block requiring permanent pacemaker implantation. Similarly, patients undergoing transcatheter aortic valve replacement are also at increased risk for developing AV block. Electrophysiologic procedures, including catheter ablation of AV nodal re-entrant tachycardia, septal accessory pathways, para-Hisian atrial tachycardia, or premature ventricular complexes, are also associated with risk of AV conduction system injury. In this article, we summarize the common causes for iatrogenic AV block, predictors for AV block, and general management considerations.

The peculiar electrophysiological properties of the sinoatrial node and the cardiac conduction system are key components of the normal physiology of cardiac impulse generation and propagation. Multiple genes and transcription factors and metabolic proteins are involved in their development and regulation. In this review, we have summarized the genetic underlying causes, key clinical findings, and the latest available clinical evidence. We will discuss clinical diagnosis and management of the genetic conditions associated with conduction disorders that are more prevalent in clinical practice, for this reason, very rare genetic diseases presenting sinus node or cardiac conduction system abnormalities are not discussed.