Introduction

In 1893, Wilhelm His Jr. discovered the physical link that electrically bridges the atria and ventricles of the heart.[1] This specialized muscle bundle connecting the atrial and ventricular chambers of the heart is now known as the bundle of His.[1] After electrical impulse is sent from the sinoatrial (SA) node to the atrioventricular (AV) node, the bundle of His quickly transmits the impulse to the left and right bundle branches and into the ventricles, resulting in a synchronized contraction of the ventricles.[2] Over the years, diseases affecting the bundle of His have been discovered along with diagnostic and therapeutic interventions.

Issues of Concern

The AV conduction system propagates electrical impulses from the atria to the ventricles to maintain proper and efficient heart function. Malfunction of this system can lead to disruption of the heart’s normal sinus rhythm, such as by inducing arrhythmias that may require critical treatment or invasive surgical procedures.[3]

Cellular Level

The bundle of His comprises of a complex organization of cells, predominantly consisting of Purkinje-type cells, slender transitional cells, broad transitional cells, and varying amounts of pacemaker cells.[2] The Purkinje-type cells of the bundle of His are composed of randomly-oriented myofibrils, an abundance of mitochondria and Golgi apparatus, and a sporadic presence of two separate nuclei.

The pacemaker (P) cells are oval in shape and contain “sparse and randomly oriented myofibrils,” simple membranes, and trivial amounts of sarcoplasmic reticulum.[2]

The bundle of His is an elongated segment connecting the AV Node and the left and right bundle branches of the septal crest. It is approximately 1.8 cm long in an adult heart[4] and is primarily located deep within the dense connective tissue.

The bundle of His is characterized by longitudinal collagen partitioning histology, distinguishing it from the AV node.[2]

The intercalated discs in the bundle of His differ from the myocardial cells such that the discs in the bundle of His are oriented obliquely compared to the perpendicular alignment seen in the myocardium cross-sectional view. The bundle of His appears to have more “tongue-and-groove joints” compared to the “jagged perpendicular line” in the myocardium. Also, more tight junctions are found in the Purkinje cells of the bundle of His than in the intercalated discs of the myocardium.[2]

Development

Although much is known about the embryological development of the heart as a whole, studies performed on the embryological development of the bundle of His are limited. The heart is derived from the lateral plate mesoderm during the third week of development. [5] As the heart continues to develop, the newly formed cardiomyocytes begin to depolarize, creating a slow electrical impulse.[3] In addition, studies show that the specialized conduction tissue in the atrioventricular canal is insulated by fibroblasts and fibrous tissue that stem from the migratory, multipotent neural crest cells.[6] The fibrous tissue, called the annulus fibrosus,  develops from the movement of the epicardial mesenchyme into the myocardial space and separates the developing atria and ventricles.[3] Further research suggests the bundle of His emerges from an interventricular ring during development.[6]

Function

Because the bundle of His is found deep within fibrous tissue, its precise function has been difficult to study. It is hypothesized that the “longitudinal partitioning of strands of the His bundle” and the abundant nexuses within the bundle of His aid the rapid conduction of the electrical signal from the AV node. Also, the encompassing collagen may potentially prevent the lateral spread of the propagated impulse.[2]

Pathophysiology

The standard bundle of His ECG is an invasive electrophysiology study which involves inserting an electrode catheter into the femoral vein, through the inferior vena cava, and into the heart. It is advanced into the right ventricle and pulled back until the continuous monitor notes a spike between the P wave and the QRS complex, signifying the depolarization of the bundle of His.[7] Newer studies have suggested that noninvasive surface electrocardiograms may be sufficient to record bundle of His potentials.[8]

Because the bundle of His transmits the electrical impulse from the AV node to the bundle branches, malfunction of the bundle of His can lead to heart blocks ranging from AV conduction delays (first-degree heart block) to a complete dissociation in the electrical conduction between the atria and ventricles (third-degree heart block). Conduction delays are a direct cause of arrhythmias, and should therefore be clinically evaluated. Although the twelve-lead electrocardiogram is the gold standard for the evaluation of cardiac arrhythmias, other modalities such as the His bundle electrocardiogram may be more useful in narrowing the source of the conduction defect. [7]

The His bundle electrocardiogram is useful in detecting the following conduction delays and clinical findings [7]:

• First-degree heart block with normal QRS above the bundle of His
• Trifascicular block with delay in conduction below the bundle of His in patients with left bundle branch block or intraventricular conduction defects
• Wenckebach (Mobitz type I) block above the bundle of His
• Mobitz type II block potentially within the bundle of His
• Mobitz type II block below the bundle of His on an ECG that shows non-conducted P waves and  intraventricular conduction defect
• Mobitz type II block with the presence of a prolonged QRS interval which may evoke intermittent trifascicular block, leading to potential complete heart block
• Second-degree AV block-conduction delay at the AV node or perinodal area-block above the bundle of His 
• Localization of second-degree AV blocks; conduction delay proximal to the bundle of His may indicate issues with the AV node, whereas conduction delay distal to the bundle of His may indicate issues with the His-Purkinje system
• Complete (third-degree) heart block that occurs within the bundle of His

Clinical Significance

There are 92.1 million Americans currently affected by some form of cardiovascular disease, and 43.9% are expected to have a type of cardiovascular disease by 2030.[9]

The bundle of His directly contributes to the pathophysiology of cardiovascular disease. Therefore, specific tools have been developed to reduce the risk of disease by manipulating the bundle of His.

His-bundle pacing (HBP) is a method in which leads are placed directly on the AV Node. This stimulates the bundle of His, generating conduction synchronization through the ventricles.[10] As ventricles return to their normal pump function, the risk of cardiomyopathy decreases.[10]

Studies show permanent direct His bundle pacing (DHBP) may be utilized in patients with chronic atrial fibrillation and dilated cardiomyopathy.[11] Additionally, studies support the use of permanent HBP as an alternative to biventricular pacing for patients who have a low success rate with left ventricular lead placement.[11][12]

In addition to detecting conduction delays, the His bundle electrocardiogram can also be utilized to examine the effect of drugs on the cardiac conduction system.[7] 

The following findings have been reported [7]:

• Vagolytic drugs, such as atropine, demonstrate a shortening between atrial depolarization and His bundle depolarization interval (P-H interval); however, they do not affect the interval between His bundle and the ventricular activation (H-Q interval)
• Isoproterenol, a sympathomimetic drug, works similarly to vagolytic drugs; a shortened P-H interval is observed, and there is no effect on the H-Q interval
• Propranolol, a sympatholytic drug, increases P-H interval without an effect on H-Q interval
• Antiarrhythmics drugs, such as lidocaine, either shorten or prolong the P-H interval with a variable effect on the H-Q interval; some patients demonstrate a modest prolongation of the intraventricular conduction 

Findings from the His bundle electrocardiogram studies suggest that the P-H interval is the most susceptible region of the conduction system to therapeutic drugs.[13]