1st Degree Atrioventricular (AV) 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] 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]

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

Pathophysiology

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.[3]

Etiology

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

Intrinsic AVN disease

Enhanced vagal tone

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.[4]

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.[4] 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.

Idiopathic degenerative diseases of conduction system

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.

Lengre 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. Lengre
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, 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.[5] In most of these
fetuses, the blocks resolved spontaneously. However, progression to a more severe degree of
block was seen in 2 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.[6]

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.[7] First-
degree AV block can occur following cardiac surgery. Transient first-degree AV block may
result from right heart catheterization.

Prognosis

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.[9] 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).[10]
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.[11] 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,

epidemiological 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.[11] 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.[12]

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.[13]

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.[14]

The Korean Heart Failure registry selected 1,986 patients with acute heart failure in sinus
rhythm and divided them into 4 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.[15]

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.[16]
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.