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.
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]
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.
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, 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.
In the United States, the prevalence of first-degree 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.[8] The overall prevalence is 1.13 cases per 1000 lives.
In a study of 2,123 patients aged 20-99 years, first-degree AV block was more prevalent among African-American patients than among Caucasian patients in all age groups except for those in the 8th decade of life.[8] 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 African-American patients occurred in the 10th decade of life, whereas the peak in Caucasian patients was in the 9th decade of life.[8]
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.
Patients with first-degree atrioventricular (AV) block are generally asymptomatic at rest. Markedly prolonged PR interval may reduce exercise tolerance in some patients with left ventricular systolic dysfunction. Syncope may result from transient high-degree AV block, especially in those with infranodal block and wide QRS complex.
Patients may have a history of past heart disease, including myocarditis or myocardial infarction (MI). Patients may be highly conditioned athletes with a high degree of vagal tone, or they may be on medications that slow conduction through the atrioventricular node (AVN).
A history of an infectious disease, such as Lyme disease, may be present. Asymptomatic first-degree heart block is part of the spectrum of presentation of Lyme carditis in children. Lyme carditis is most likely in children with Lyme disease who are older than 10 years of age, those with arthralgias, and those with cardiopulmonary symptoms.[10]
Borderline first-degree AV block in patients with long-standing systemic lupus erythematosus (SLE) may be a clue to more significant cardiac disease, resulting from the progression of SLE; these patients require careful screening for underlying myocardial disease.[17] Conduction disturbances may also be secondary to drugs used to treat SLE.
Patients who have undergone mitral valve replacement or mitral valve annuloplasty may have heart block postoperatively.[18]
No findings on the physical examination are specifically associated with first-degree AV block; it is generally an incidental finding noted on an electrocardiogram (ECG).
The intensity of the first heart sound (S1) is decreased in patients with first-degree AV block. Patients with first-degree AV block may have a short, soft, blowing, diastolic murmur heard at the cardiac apex. This diastolic murmur is not caused by diastolic mitral regurgitation, because it reaches its peak before the onset of regurgitation. The diastolic murmur is thought to be related to antegrade flow through closing mitral valve leaflets that are stiffer than normal.[19] Administration of atropine may reduce the duration of this murmur by shortening the PR interval.
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 the following[20] :
Reduction in left ventricular stroke volume and cardiac output
First-degree atrioventricular (AV) block is frequently noted as an incidental finding on electrocardiography (ECG).
Routine laboratory studies are usually not indicated in the evaluation of first-degree AV block. Electrolyte and drug screen can be obtained if a metabolic derangement or drug toxicity is suspected. Routine imaging studies are not indicated for first-degree AV block.
On a surface ECG, the PR interval exceeds 200 msec, and all P waves conduct to the ventricle with constant but prolonged PR interval (see the images below).
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The PR interval is 0.24 seconds (240 ms) in this patient with asymptomatic first-degree atrioventricular block.
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ECG in a patient with first-degree heart block.
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ECG in patient with first-degree heart block.
His bundle ECG is necessary only in patients with symptomatic (ie, presyncope and syncope) first-degree AV block and a wide QRS complex, indicative of bundle-branch block. The study is used to locate the site of the block in these patients. As many as 50% of patients show an infranodal conduction delay.
Follow-up ECGs may be indicated in patients who are treated with AV nodal agents while in the emergency department (ED), as well as for patients with a concomitant myocardial infarction (MI).
In patients with first-degree AV block and left ventricular systolic dysfunction, Doppler ultrasonography may be used to document an improvement in cardiac output during dual-chamber pacing at short AV delay. This may provide evidence for the appropriateness of implanting a permanent pacemaker for hemodynamic support in such patients.
More recently, cardiac resynchronization therapy (ie, biventricular pacing) has been applied in patients with cardiomyopathy, congestive heart failure, or intraventricular conduction delay (IVCD).[21] First-degree AV block is frequently present in these patients as well.
Under light microscopy, an atrioventricular node (AVN) is seen to be composed of a thick mesh of tiny pale cells, which anastomose with one another via short pluridirectional cytoplasmic projections. Under electron microscopy, 4 types of cells are observed in the AVN: transitional cells, P cells, common myocardial cells, and Purkinje cells.
Three functional regions have been described in the AVN on the basis of their differing conductive properties: atrionodal (AV), nodal (N), and nodal-His (NH). Cells in the N region have slower conduction times than the other regions and have no automaticity properties. Cells of the AN and NH regions have faster conduction times and display spontaneous diastolic repolarization activity.
In general, no treatment is indicated for asymptomatic isolated first-degree atrioventricular (AV) heart block.
For patients with marked first-degree AV block (PR interval > 300 msec), however, several uncontrolled trials have demonstrated symptomatic improvement with placement of a dual-chamber pacemaker, though there is little evidence suggesting improved survival.[2] in patients with severe bradycardia or those with the possibility of progression to higher-degree AV block, medications (eg, atropine, isoproterenol) can be used in anticipation of insertion of a cardiac pacemaker.
Any associated condition (eg, myocardial infarction [MI], digitalis intoxication) should be treated appropriately. Significant electrolyte abnormalities should be corrected.
In patients with symptomatic first-degree AV block, discontinue medications with potential for AV block, if possible. Electrophysiology consultation may be indicated for patients with first-degree AV block and symptoms of syncope or heart failure.
In general, hospitalization specifically for first-degree AV block is not indicated. However, admission may be indicated for associated conditions (eg, MI). Patients with a marked first-degree AV block can present with symptoms similar to the pacemaker syndrome.[2] In these individuals, admission may be indicated.
According to guidelines from the American College of Cardiology (ACC), the American Heart Association (AHA), and the Heart Rhythm Society (HRS), permanent pacemaker implantation is reasonable for first-degree AV block with symptoms similar to those of pacemaker syndrome or hemodynamic compromise (class IIa recommendation; level of evidence, B).[22] Additional ACC/AHA/HRS recommendations have been formulated for other patients with first-degree AV block, as follows.
Patients with first-degree AV block, with or without symptoms, may be considered for permanent pacemaker implantation if the block occurs in the setting of neuromuscular diseases such as myotonic muscular dystrophy, Erb dystrophy (limb-girdle muscular dystrophy), or peroneal muscular atrophy, because these patients may experience unpredictable progression of AV conduction disease ( class IIb recommendation, level of evidence, B).
Permanent pacemaker implantation is not indicated for asymptomatic first-degree AV block (class III recommendation; level of evidence, B).
In the absence of a disease process that requires admission, patients with first-degree AV block may be safely discharged and receive follow-up on an outpatient basis. Patients should get serial follow-up electrocardiograms (ECGs) to evaluate for progression to a higher-grade AV block.
Patients with first-degree AV block started on atrioventricular node (AVN)-blocking drugs should be monitored to make sure that higher-grade AV block does not develop. Patients with first-degree AV block and coexistent bundle-branch block should be closely observed.
Use of medication is not indicated for treatment of asymptomatic first-degree atrioventricular (AV) block. However, in patients with severe bradycardia or those with the possibility of progression to higher-degree AV block, medications (eg, atropine, isoproterenol) can be used in anticipation of insertion of a cardiac pacemaker.
Clinical Context:
Isoproterenol has beta1- and beta2-adrenergic receptor activity. It binds the beta-receptors of the heart, smooth muscle of bronchi, skeletal muscle, vasculature, and the alimentary tract. It has positive inotropic and chronotropic actions.
Isoproterenol infusion can be used to shorten AV conduction time. Isoproterenol has chronotropic as well as inotropic effects, which result in an increase in cardiac output.
Jamshid Alaeddini, MD, FACC, FHRS, Director, Cardiac Electrophysiology Services, Lake Health System
Disclosure: Nothing to disclose.
Coauthor(s)
Jamshid Shirani, MD, Director of Cardiology Fellowship Program, Director of Echocardiography Laboratory, Director of Hypertrophic Cardiomyopathy Clinic, St Luke's University Health Network
Disclosure: Nothing to disclose.
Michael D Levine, MD, Assistant Professor, Department of Emergency Medicine, Section of Medical Toxicology, Keck School of Medicine of the University of Southern California
Disclosure: Nothing to disclose.
Theodore J Gaeta, DO, MPH, FACEP, Clinical Associate Professor, Department of Emergency Medicine, Weill Cornell Medical College; Vice Chairman and Program Director of Emergency Medicine Residency Program, Department of Emergency Medicine, New York Methodist Hospital; Academic Chair, Adjunct Professor, Department of Emergency Medicine, St George's University School of Medicine
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Brian Olshansky, MD, FESC, FAHA, FACC, FHRS, Professor Emeritus of Medicine, Department of Internal Medicine, University of Iowa College of Medicine
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Amarin; Lundbeck; Respircardia; Sanofi Aventis<br/>Serve(d) as a speaker or a member of a speakers bureau for: Sanofi Aventis<br/>Boehringer Ingelheim – co-coordinator of GLORIA AF registry.
Chief Editor
Jeffrey N Rottman, MD, Professor of Medicine, Department of Medicine, Division of Cardiovascular Medicine, University of Maryland School of Medicine; Cardiologist/Electrophysiologist, University of Maryland Medical System and VA Maryland Health Care System
Disclosure: Nothing to disclose.
Additional Contributors
Eddy S Lang, MDCM, CCFP(EM), CSPQ, Associate Professor, Senior Researcher, Division of Emergency Medicine, Department of Family Medicine, University of Calgary Faculty of Medicine; Assistant Professor, Department of Family Medicine, McGill University Faculty of Medicine, Canada
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