First-Degree Atrioventricular Block

First-degree atrioventricular (AV) block, or first-degree heart block, is defined as prolongation of the PR interval on an electrocardiogram (ECG) to more than 200 msec. ^{[1, 2]} The PR interval of the surface ECG is measured from the onset of atrial depolarization (P wave) to the beginning of ventricular depolarization (QRS complex). Normally, this interval should be between 120 and 200 msec in the adult population. First-degree AV block is considered “marked” when the PR interval exceeds 300 msec ^{[2, 3]} ; the P waves may be buried in the preceding T wave. ^[2]

Whereas conduction is slowed, there are no missed beats. ^[2] In first-degree AV block, every atrial impulse is transmitted to the ventricles, resulting in a regular ventricular rate. ^[2]

The atrioventricular node (AVN) is the only normal electrical connection between the atria and the ventricles. It is an oval or elliptical structure, measuring 7-8 mm in its longest (anteroposterior) axis, 3 mm in its vertical axis, and 1 mm transversely. The AVN is located beneath the right atrial endocardium, dorsal to the septal leaflet of the tricuspid valve, and about 1 cm superior to the orifice of the coronary sinus.

The bundle of His originates from the anteroinferior pole of the AVN and travels through the central fibrous body to reach the dorsal edge of the membranous septum. It then divides into right and left bundle branches. The right bundle continues first intramyocardially, then subendocardially, toward the right ventricular apex. The left bundle continues distally along the membranous septum and then divides into anterior and posterior fascicles.

Blood supply to the AVN is provided by the AVN artery, a branch of the right coronary artery in 90% of individuals and of the left circumflex coronary artery in the remaining 10%. The His bundle has a dual blood supply from branches of anterior and posterior descending coronary arteries. Likewise, the bundle branches are supplied by both left and right coronary arteries.

The AVN has a rich autonomic innervation and is supplied by both sympathetic and parasympathetic nerve fibers. This autonomic innervation has a major role in the time required for the impulse to pass through the AVN.

The PR interval represents the time needed for an electrical impulse from the sinoatrial (SA) node to conduct through the atria, the AVN, the bundle of His, the bundle branches, and the Purkinje fibers. Thus, as shown in electrophysiologic studies, PR interval prolongation (ie, first-degree AV block) may be due to conduction delay within the right atrium, the AVN, the His-Purkinje system, or a combination of these.

Overall, dysfunction at the AVN is much more common than dysfunction at the His-Purkinje system. If the QRS complex is of normal width and morphology on the ECG, then the conduction delay is almost always at the level of the AVN. If, however, the QRS demonstrates a bundle-branch morphology, then the level of the conduction delay is often localized to the His-Purkinje system.

Occasionally, the conduction delay can be the result of an intra-atrial conduction defect. Some causes of atrial disease resulting in a prolonged PR interval include endocardial cushion defects and Ebstein anomaly. ^[4]

The following are the most common causes of first-degree atrioventricular (AV) block:

• Intrinsic AV node (AVN) disease

• Enhanced vagal tone ("pathophysiologic AV block" ^[2] )

• Acute myocardial infarction (MI), particularly acute inferior wall MI

• Myocarditis

• Electrolyte disturbances (eg, hypokalemia, hypomagnesemia)

• Drugs (especially those drugs that increase the refractory time of the AVN, thereby slowing conduction)

A number of specific disorders and events have been implicated (see below).

Athletic training

Well-trained athletes can demonstrate first-degree (and occasionally higher degree) AV block owing to an increase in vagal tone.

Coronary artery disease

Coronary artery disease is a factor. First-degree AV block occurs in fewer than 15% of patients with acute MI admitted to coronary care units. His bundle electrocardiographic studies have shown that, in most of these patients, the AVN is the site of conduction block.

AV block is more common in the setting of inferior MI. In the Thrombolysis in Myocardial Infarction (TIMI) II study, high-degree (second- or third-degree) AV block occurred in 6.3% of patients at the time of presentation and in 5.7% in the first 24 hours after thrombolytic therapy. ^[5]

Patients with AV block at the time of presentation had a higher in-hospital mortality than patients without AV block; however, the 2 groups had similar mortalities during the following year. ^[5] Patients who developed AV block after thrombolytic therapy had higher mortalities both in hospital and during the following year than patients without AV block. The right coronary artery was more often the site of infarction in patients with heart block than in those without heart block.

Patients with AV block are believed to have larger infarct size. However, the prevalence of multivessel disease is not higher in patients with AV block.

In a systematic review and meta-analysis comprising 14 studies undertaken between 1972 and 2011, with 400,750 participants, Kwok et al found evidence that prolonged PR interval is associated with adverse cardiovascular outcomes and mortality. ^[6] In their meta-analysis, data from observational studies suggested a possible association between prolonged PR interval and significant increases in atrial fibrillation, heart failure, and mortality. ^[6]

Idiopathic degenerative diseases of conduction system

Diseases that involve sclerosis of the conduction system (eg, Lev disease, Lenègre disease) can also cause AV block. ^[2]

Lev disease is due to progressive degenerative fibrosis and calcification of the neighboring cardiac structures, or “sclerosis of the left side of cardiac skeleton” (including the mitral annulus, central fibrous body, membranous septum, base of the aorta, and crest of the ventricular septum). Lev disease has an onset about the fourth decade and is believed to be secondary to wear and tear on these structures caused by the pull of the left ventricular musculature. It affects the proximal bundle branches and is manifested by bradycardia and varying degrees of AV block.

Lenègre disease is an idiopathic, fibrotic degenerative disease restricted to the His-Purkinje system. It is caused by fibrocalcareous changes in the mitral annulus, membranous septum, aortic valve, and crest of the ventricular septum. These degenerative and sclerotic changes are not attributed to inflammatory or ischemic involvement of adjacent myocardium. Lenègre disease involves the middle and distal portions of both bundle branches and affects a younger population than Lev disease does.

Drugs

Drugs that most commonly cause first-degree AV block include the following:

• Class Ia antiarrhythmics (eg, quinidine, procainamide, disopyramide)

• Class Ic antiarrhythmics (eg, flecainide, encainide, propafenone)

• Class II antiarrhythmics (beta-blockers)

• Class III antiarrhythmics (eg, amiodarone, sotalol, dofetilide, ibutilide)

• Class IV antiarrhythmics (calcium channel blockers)

• Digoxin or other cardiac glycosides

• Magnesium

Although first-degree AV block is not an absolute contraindication for administration of drugs such as calcium channel blockers, beta-blockers, digoxin, and amiodarone, extreme caution should be exercised in the use of these medications in patients with first-degree AV block. Exposure to these drugs increases the risk of developing higher-degree AV block.

Mitral or aortic valve annulus calcification

The main penetrating bundle of His is located near the base of the anterior leaflet of the mitral valve and the noncoronary cusp of the aortic valve. Heavy calcium deposits in patients with aortic or mitral annular calcification is associated with increased risk of AV block.

Infectious disease

Infective endocarditis, diphtheria, rheumatic fever, Chagas disease, Lyme disease, coronavirus disease 2019 (SARS-CoV-2, COVID-19) ^[7] and tuberculosis all may be associated with first-degree AV block. Extension of the infection to the adjacent myocardium in native or prosthetic valve infective endocarditis (ie, ring abscess) can cause AV block. Acute myocarditis caused by diphtheria, rheumatic fever, or Chagas disease can result in AV block.

Collagen vascular disease

Rheumatoid arthritis, systemic lupus erythematosus (SLE), and scleroderma all may be associated with first-degree AV block. Rheumatoid nodules may occur in the central fibrous body and result in AV block. Fibrosis of the AVN or the adjacent myocardium in patients with SLE or scleroderma can cause first-degree AV block.

Doppler echocardiographic signs of first-degree AV block have been demonstrated in about 33% of fetuses of pregnant women who are anti-SSA/Ro 52-kd positive. ^[8] In most of these fetuses, the blocks resolved spontaneously. However, progression to a more severe degree of block was seen in two of the fetuses. Serial Doppler echocardiographic measurement of AV-time intervals can be used for surveillance of these high-risk pregnancies.

Iatrogenesis

First-degree AV block occurs in about 10% of patients who undergo adenosine stress testing and is usually hemodynamically insignificant. Patients with baseline first-degree AV block more often develop higher degrees of AV block during adenosine stress testing. These episodes, however, are generally well tolerated and do not require specific treatment or discontinuance of the adenosine infusion. ^[9]

Marked first-degree AV block may occur after catheter ablation of the fast AVN pathway with resultant conduction of the impulse via the slow pathway. This may result in symptoms similar to those of the pacemaker syndrome.

First-degree AV block (reversible or permanent) has been reported in about 2% of patients who undergo closure of an atrial septal defect using the Amplatzer septal occluder. ^[10] First-degree AV block can occur following cardiac surgery. Transient first-degree AV block may result from right heart catheterization.

Infiltrative disease (sarcoidosis)

Infiltrative disease, such as sarcoidosis, may involve the cardiac conduction system as well as other organ systems. Cardiac sarcoidosis may precede, follow, or occur concurrently with involvement of the lungs or other organs. Symptomatic cardiac involvement is estimated to occur in 2-7% of patients with sarcoidosis. Conduction abnormalities may range from first-degree heart block to complete heart block (25-30%). ^[11] Sustained or nonsustained ventricular tachycardia is also common in patients with cardiac sarcoidosis and, along with complete heart block, are the most common causes of sudden cardiac death in patients with cardiac sarcoidosis.

United States data

In the United States, the prevalence of first-degree atrioventricular (AV) block among young adults ranges from 0.65% to 1.6%. Higher prevalence (8.7%) is reported in studies of trained athletes. The prevalence of first-degree AV block increases with advancing age; first-degree AV block is reported in 5% of men older than 60 years, ^[12]  with an approximate 2 to 1 ratio of males to females. ^[13] The overall prevalence is 1.13 cases per 1,000 lives.

In a study of 2,123 patients aged 20-99 years, first-degree AV block was more prevalent among black patients than among white patients in all age groups except for those in the 8th decade of life. ^[12] In this study, the prevalence of first-degree AV block increased at age 50 years in both ethnic groups and gradually increased with advancing age. The peak in black patients occurred in the 10th decade of life, whereas the peak in white patients was in the 9th decade of life. ^[12]

International data

In a study of the prevalence of first-degree AV block in rural Northeast China (2017-2018) among 10,926 participants at least 40 years old, investigators noted the prevalence was 3.4% with a male predominance. ^[14] Independent risk factors for first-degree AV block included male sex, older age, taller height, elevated systolic blood pressure and triglyceride levels, reduced high-density lipoprotein cholesterol level, heart rate, and lack of regular exercise. ^[14]

The prognosis for isolated first-degree AV block usually is very good. Progression from isolated first-degree heart block to high-degree block is very uncommon. ^[15] Patients with first-degree AV block and infranodal blocks, however, are at increased risk for progression to complete AV block.

Heart block in children with Lyme carditis tends to resolve spontaneously, with median recovery in 3 days (range, 1-7 days). ^[16]

Cheng et al found that first-degree heart block is associated with increased long-term risks of atrial fibrillation, pacemaker implantation, and all-cause mortality. ^[17] Their community-based cohort included 7575 individuals from the Framingham Heart Study who underwent baseline routine 12-lead ECG in 1968-1974 and were followed prospectively through 2007.

Traditionally, first-degree AV block has been considered a benign condition. However, epidemiologic data from the Framingham Study have shown that first-degree AV block is associated with increased risk of all-cause mortality in the general population. Compared with individuals whose PR intervals were 200 msec or shorter, those with first-degree AV block had a 2-fold adjusted risk of atrial fibrillation, a 3-fold adjusted risk of pacemaker implantation, and a 1.4-fold adjusted risk of all-cause mortality. ^[17] Each 20-msec increment in PR interval was associated with an adjusted hazard ratio (HR) of 1.11 for atrial fibrillation, 1.22 for pacemaker implantation, and 1.08 for all-cause mortality. ^[18]

A study by Uhm et al of 3816 patients indicated that in the presence of hypertension, patients with first-degree AV block have a greater risk of developing advanced AV block, atrial fibrillation, and left ventricular dysfunction than do hypertensive patients with a normal PR interval. ^[19]

Crisel showed that patients with stable coronary artery disease who had a PR of 220 msec or more had a significantly higher risk of reaching the combined end point of heart failure or cardiovascular death over a follow-up of 5 years. ^[20]

The Korean Heart Failure registry selected 1,986 patients with acute heart failure in sinus rhythm and divided them into four groups, depending on the presence of first-degree AV block and/or QRS prolongation. During the median follow-up of 18.2 months, overall death rate was highest in patients who had both first-degree AV block and prolonged QRS. This group also showed worst outcomes regarding the requirement of invasive managements during the index admission, in-hospital mortality, post discharge death/rehospitalization, and cardiac device implantation. ^[18]

In an analysis of the COMPANION Trial, 1520 patients fulfilling criteria for cardiac resynchronization therapy (CRT) implant were assigned to normal (PR < 200 msec) or prolonged (PR ≥200 msec) AV delay and cohorts were compared within the optimal pharmacologic therapy and CRT groups regarding an endpoint of all-cause mortality or heart failure hospitalization. CRT was compared with optimal pharmacologic therapy in normal and prolonged PR interval groups. Randomization to CRT was associated with a reduction in the endpoint in all patients; the strength of the association was greater for those with first-degree AV block versus normal PR intervals. This analysis demonstrated that the deleterious effect of first-degree AV block in patients with systolic dysfunction, heart failure, and wide QRS complexes be attenuated by CRT. ^[21]

More recently, a 2018 subgroup analysis from the INSIGHT XT study that evaluated the outcomes of patients with baseline first-degree AV block who received an insertable cardiac monitor (ICM) found the presence or progression to a higher grade block in 53% of patients or detected an already existing more severe bradycardia that warranted an IPG in 40.5% of patients. ^[22] The findings led the investigators to conclude first-degree AV block may be a risk marker for more severe intermittent conduction disease.

These studies suggest that first-degree AV block is not necessarily a benign condition. In patients with chronic systolic heart failure and wide QRS, CRT may attenuate its deleterious effect.

Complications

Patients with first-degree AV block can occasionally progress to higher-grade AV blocks. Usually, such a progression is only to Mobitz I second-degree heart block, but occasionally, higher-grade block can occur. The later scenario is particularly seen in patients with an acute MI, myocarditis, or acute drug overdoses.

Drugs that slow conduction through the AVN system increase the risk of progression to higher-grade heart blocks. Administering such agents to a person with a coexisting first-degree AV block should be done with caution.

Other potential complications include reduction in left ventricular stroke volume and cardiac output due to loss of the atrial contribution to ventricular contraction, as well as pacemaker syndrome. ^[23]

In pacemaker syndrome, which can follow placement of a pacemaker, patients with very prolonged PR interval, especially in those with PR intervals longer than 300 msec, may experience the atrial contraction occurring too close to the previous ventricular contraction (ie, loss of AV synchrony). ^[24] If the atrial contraction occurs while the atrioventricular valves are closed, it can result in a significant increase in atrial pressures, which leads to a reversal of blood flow and abnormal pressure waves. Most of the signs and symptoms of pacemaker syndrome are nonspecific, but it may present as dizziness, near syncope, syncope, shortness of breath, chest pain, a feeling of neck tightness, and hypotension.