Premature atrial contractions and junctional premature beats in adults

INTRODUCTION — 

Supraventricular premature beats (SPBs) include:

●Premature atrial contractions (PACs; also referred to as premature atrial beats, premature supraventricular complexes, or premature supraventricular beats) which originate from the atria. The vast majority of SPBs are atrial in origin.

and

●Junctional premature beats (JPBs; also known as premature junctional contractions or complexes) which originate from the atrioventricular (AV) node.

The prevalence, mechanisms, clinical manifestations, diagnosis, and treatment of SPBs will be presented here.

A discussion of premature ventricular complexes (PVCs; also referred to a premature ventricular contractions, premature ventricular beats or premature ventricular depolarizations) is presented separately. (See "Premature ventricular complexes: Clinical presentation and evaluation".)

PREVALENCE

Prevalence of PACs — PACs are nearly ubiquitous, occurring commonly in adults with and without heart disease, with increasing prevalence with older age [1-4].

The reported prevalence of PACs is highly dependent upon the duration of observation (eg, PACs are less commonly identified on standard 10-second 12-lead electrocardiograms [ECGs] compared with 24-hour or longer-duration ambulatory [Holter] ECG recordings). In a cross-sectional population study of 1742 Swiss adults (50 years of age or older) who underwent Holter monitoring for 24 hours, 99 percent had at least one PAC during the monitoring period [1]. The frequency of PACs increased with age, with rates of 0.8, 1.4, and 2.6 PACs per hour among participants aged 50 to 55 years, 60 to 65 years, and 70 or more years, respectively.

Additional causes of the wide range of PAC prevalence rates are day-to-day variability as well as circadian variation. In the Copenhagen Holter Study cohort, in which 638 individuals (ages 55 to 75 years) underwent up to 48-hour Holter recording and were followed for a median of 14 years, circadian variation was observed in the group with frequent PACs (≥720/day; n = 66 persons), with the fewest PACs/h observed during the night with a nadir at 6 AM and then reaching a peak value in the afternoon at 3 PM. Runs of PACs in all subjects showed a similar circadian variation, while the risk of atrial fibrillation (AF) was similar among time intervals throughout the day [5].

Associations between PAC frequency and clinical conditions and exposures are discussed below. (See 'Etiology' below.)

Prevalence of JPBs — JPBs occur less commonly than both PACs and PVCs. JPBs occur in individuals with normal or abnormal hearts. Their prevalence has not been well studied due in part to their scarcity as well as difficulty in correctly identifying them. In addition, many studies combine JPBs and PACs into one category of SPBs.

ETIOLOGY

PACs — The incidence of PACs is increased with a variety of medical conditions and exposure. However, it can be challenging to identify a relationship between PACs and these conditions since PACs occur frequently and variably in individuals with and without these exposures and conditions.

Clinical conditions and medications — The incidence of PACs is increased in patients with a broad range of acute and chronic clinical conditions and medication exposures, including the following examples:

●Electrolyte disorders and hypoxemia – Frequent PACs are among the arrhythmias seen in patients with hypokalemia, hypomagnesemia, and/or hypoxemia, as discussed separately. (See "Clinical manifestations and treatment of hypokalemia in adults", section on 'Cardiac arrhythmias and ECG abnormalities' and "Hypomagnesemia: Clinical manifestations of magnesium depletion", section on 'Cardiovascular manifestations' and "Arrhythmias in COPD", section on 'Hypoxemia and respiratory acidosis'.)

●Cardiovascular disease – PACs are commonly seen in patients with cardiovascular disease (CVD), particularly with conditions associated with elevated left and/or right atrial pressures and atrial dilation. Examples include hypertension, valvular heart disease (eg, mitral valve disease), ischemic heart disease, and cardiomyopathies (eg, cardiac amyloidosis) [6-8].

•Atrial myopathy – Some studies have suggested that an atrial myopathy is an underlying disorder in individuals at risk for cardioembolic stroke with or without AF [9-12]. Atrial stretching, inflammation and/or other processes associated with aging may cause atrial remodeling, which in some individuals might increase the risk of left atrial thrombogenesis even in the absence of AF [9-12]. Proposed markers of atrial myopathy include echocardiographic indices, biomarkers of inflammation, fibrosis, endothelial dysfunction, and heavy or excessive burden of PACs (eg, ≥30 PACs/h daily or ≥200 PACs/24 h, or any runs of ≥20 PACs) [9,10,13,14].

Conversely, some investigators have suggested that frequent PACs impair left atrial contractile function and promote adverse atrial remodeling and may thus be responsible for the development of atrial myopathy [15]. Atrial myopathy should be suspected in patients with excessive PAC burden. In such patients, evaluation includes echocardiography. A role for anticoagulation in this setting has not been established [11].

•Hypertension – Hypertension is one of the conditions contributing to the development of atrial myopathy [12]. An observational study in 4697 adults (mean age 62) with hypertension without other history of CVD found that individuals with systolic blood pressure (SBP) ≤140 mmHg had a lower prevalence of PACs than those with SBP >140 mmHg (1.1 versus 1.9 percent). In a multivariable-adjusted model, each 10 mmHg decrease in SBP was associated with a 12 percent reduction in odds of PACs (odds ratio 0.88, 95% CI 0.77-0.99). The presence of PACs was associated with an increased risk of CVD mortality in a multivariable-adjusted Cox model.

•Coronary artery disease

-Acute MI – Patients with acute myocardial infarction (MI) have an early increase in the frequency of PACs, with an incidence ranging from 25 to 81 percent [1,16,17]. One study noted a mean of 9 to 14 PACs per hour on day 1 post-MI, which decreased to one to two PACs per hour on day 10 post-MI [16]. Paroxysmal supraventricular tachycardia and junctional tachycardia after MI are discussed separately. (See "Supraventricular arrhythmias after myocardial infarction".)

-Exercise testing – Among patients with known or suspected coronary artery disease, PACs are commonly induced during exercise testing, but the prognostic importance of this finding is uncertain [18]. Some studies have found an association between detection of PACs during exercise testing and clinical identification of AF during subsequent months and years [19,20].

-However, as noted below, the association between PACs and later development of AF has been also been observed in individuals without obstructive coronary artery disease. (See 'AF' below and "Prognostic features of stress testing in patients with known or suspected coronary disease", section on 'Atrial arrhythmias'.)

•Inflammatory conditions – PACs and JPBs are among the arrhythmias that may occur in patients with pericarditis or myocarditis.

•Obstructive hypertrophic cardiomyopathy (HCM) – Electrical and structural remodeling in the atria is more advanced in patients with HCM compared with patients with hypertensive heart disease and/or athletes [21]. The incidence of postoperative AF may be significantly higher (approximately 20 percent) in patients with obstructive HCM who have a high burden of PACs preoperatively [22,23].

●Chronic obstructive pulmonary disease (COPD) – Supraventricular arrhythmias (as well as ventricular arrhythmias) are common among patients with chronic obstructive pulmonary disease (COPD), as discussed separately (see "Arrhythmias in COPD"). Multiple factors contribute to the development of arrhythmias in patients with COPD, including hypoxemia, respiratory acidosis, electrolyte disorders, medications (eg, theophylline and beta-agonist bronchodilators [24-26]), and comorbidities (including hypertension, coronary artery disease, and heart failure).

●Drugs – Limited evidence is available on drug effects on PAC frequency. Medications that may trigger or increase the frequency of PACs include adrenergic agents (eg, beta-agonists bronchodilators, epinephrine, and isoproterenol) and digoxin.

Illicit recreational stimulant drugs such as cocaine, amphetamines, and methamphetamine may increase the frequency of PACs, but data are limited [27].

Lifestyle risk factors — Common exposures such as smoking tobacco and alcohol consumption may increase the frequency of PACs [28-31]. Other factors influencing PAC frequency comprise age, height, heart rate, physical activity, and triglycerides [32].

●Smoking – Smoking tobacco increases sympathetic tone, which may affect PAC frequency [28,30]. A small study found that smoked tobacco was associated with an acute increase in frequency of both PACs and PVCs [30].

●Alcohol – Alcohol consumption may also increase the frequency of PACs, although the findings of observational studies have been mixed [31]. A prospective study of 202 volunteers identified increases in heart rate and atrial arrhythmias with increasing amounts of acute alcohol consumption [33]. The drinking period was defined as hours 1 to 5 after baseline and the recovery period was hours 6 to 19 after baseline. PACs were more frequent during the two control periods (after the drinking period and after the recovery period) in contrast to PVCs, which were more frequent during the drinking period. Ten participants experienced more extended arrhythmias (eg, AF and nonsustained ventricular tachycardia), mainly during the recovery period.

Arrhythmias associated with alcohol-induced cardiomyopathy are discussed separately. (See "Alcohol-induced cardiomyopathy", section on 'Arrhythmias'.)

●Elevated BMI and limited physical activity – An analysis of data on 1924 participants from the Atherosclerosis Risk in Communities (ARIC) Study found that elevated body mass index (BMI) and limited physical activity in midlife were associated with elevated frequency of PACs in later life [34].

On the other hand, the frequency of PACs may be increased during physical activity, as described below.

Lack of association with caffeine — In contrast, caffeine has not been demonstrated to be proarrhythmic, although caffeine intake may be associated with palpitations [35,36]. Acute or chronic caffeine intake has not been shown to influence the frequency of PACs, as illustrated by the following studies:

●Acute caffeine intake – A randomized case-crossover trial in 100 adults found that consumption of caffeinated coffee (compared with no caffeine consumption) was associated with no increase in daily PACs (58 versus 53 per day; rate ratio 1.09, 95% CI 0.98-1.20) but was associated with an increase in daily PVCs (154 versus 102; rate ratio 1.51, 95% CI 1.18-1.94) [37].

●Chronic use of caffeine – In a study of 1388 participants in the Cardiovascular Health Study, in which caffeine consumption was self-reported and patients underwent 24-hour ambulatory monitoring, there was no significant difference in the frequency of PACs between chronic users and nonusers of caffeine [38]. With dietary intake of coffee, tea, and chocolate analyzed as a continuous measure with multivariable adjustment, no relationships with PACs or PVCs were observed.

However, there may be patients who are more sensitive to caffeine and note a relationship between palpitations and caffeine intake.

JPBs — The limited available data on JPBs suggest that conditions and exposures that trigger or increase the frequency of JPBs are similar to those that increase PACs. These include hypokalemia, digitalis toxicity, coronary artery disease, COPD, valvular heart disease, pericarditis, heart failure, hyperthyroidism, and cardiac surgery (attributed to inflammatory changes in the AV junction following surgery), smoking tobacco, alcohol consumption, and amphetamine use.

MECHANISMS — 

Since invasive testing is rarely performed in patients with only simple PACs, there is scant information about the mechanisms of PACs in humans. Although the mechanisms responsible for spontaneous PACs have not been well investigated, it seems likely that multiple mechanisms are responsible for PACs in different clinical settings. The following are possible mechanisms, as discussed in greater detail separately:

●Reentry within the atrium [39] (see "Reentry and the development of cardiac arrhythmias")

●Abnormal automaticity [40] (see "Enhanced cardiac automaticity")

●Triggered activity [41] (see "Cardiac excitability, mechanisms of arrhythmia, and action of antiarrhythmic drugs")

Although the mechanisms responsible for JPBs are not clear or well investigated, JPBs are most likely caused by abnormal automaticity. (See "Enhanced cardiac automaticity".)

CLINICAL MANIFESTATIONS — 

The presence of PACs or JPBs is associated with several characteristic findings on history, physical examination, and ECG.

Symptoms and signs — PACs or JPBs may be asymptomatic or cause symptoms such as a sensation of "skipping" or palpitations. PACs or JPBs are often single and isolated, but they may occur in a bigeminal pattern and may be frequent.

PACs or JPBs produce no or few symptoms in the vast majority of individuals. PACs or JPBs may cause palpitations (when there is a pause and increased left ventricular inotropy resulting from an increase in stroke volume) or the sensation of skipped beats which may be due to nonconducted PACs or ineffective contraction resulting from poor filling of the left ventricle during the premature beat. Atrial bigeminy with nonconducted PACs may lead to ventricular rates approaching 40 beats/min, possibly leading to symptoms (ie, lightheadedness, dizziness, presyncope) related to the bradyarrhythmia (waveform 1). Concealed JPBs that lead to second-degree AV block may be associated with symptoms of lightheadedness or near syncope, particularly if they occur in a bigeminal pattern.

In patients with PACs and/or JPBs, the most common physical finding is an irregular arterial pulse. PACs, JPBs, and PVCs cause irregular cannon a waves on jugular venous examination.

Complications — Although PACs or JPBs have an array of manifestations, they are not life-threatening by themselves. In predisposed individuals, PACs may initiate supraventricular and, less commonly, ventricular arrhythmias, with AF being the most common arrhythmia induced by PACs [42-45]. (See "Mechanisms of atrial fibrillation", section on 'Role of premature atrial complex and other arrhythmia triggers'.)

Frequent PACs can cause a reversible cardiomyopathy in animal models, with only rare case reports of humans with incessant PACs presenting with symptoms of heart failure [46]. This is discussed in more detail separately. (See "Arrhythmia-induced cardiomyopathy", section on 'Frequent atrial ectopy'.)

Physical examination — The most characteristic finding on physical examination is the presence of an irregular pulse resulting from the presence of PACs or JPBs during the examination. Palpation of the peripheral pulse will demonstrate either premature pulse waves or pauses.

Early PACs may lead to cannon A waves on the jugular venous pulsations as they may occur while the AV valves are still closed from the previous ventricular systole. This finding may be particularly helpful in differentiating early nonconducted PACs from sinus pauses. (See "Examination of jugular venous waveforms", section on 'Impact on a-waves'.)

Auscultation of the heart may detect early heart sounds or pauses. PACs and JPBs may also lead to changes in the intensity or timing of a variety of cardiac murmurs (such as those due to mitral valve prolapse) due to the reduction in diastolic filling time and a reduction in ventricular volumes. These changes may be reversed with the post-extrasystolic beat since there is an increase in ventricular volume due to the pause. (See "Auscultation of cardiac murmurs in adults: General concepts and systolic murmurs".)

DIAGNOSTIC EVALUATION

Initial tests — The evaluation of patients with symptoms suggesting PACs or JPBs should focus on documenting their presence or absence with a 12-lead ECG or some form of ambulatory cardiac monitoring. (See 'Electrocardiography' below.)

Diagnosis

Electrocardiography — A 12-lead ECG is a key diagnostic test for any patient with suspected PACs or JPBs.

ECG findings with PACs — A diagnosis of a PAC is made when a P wave with a morphology and axis different from that of the sinus P wave (eg, inverted or biphasic) occurs earlier than the anticipated sinus P wave (waveform 2).

●PAC morphology – If the ectopic focus for the PAC is near the sinus node, the P wave morphology may be like that of the sinus P wave. However, every lead should be examined as subtle differences in morphology between ectopic P waves and sinus P waves may be present.

The site of origin of a PAC affects its morphology:

•A negative P wave in the inferior leads, particularly aVF, suggests a low atrial focus. A PAC originating in the low right atrium near the AV node may result in a short PR interval (<120 ms) and may even be mistaken for a junctional premature depolarization.

•A negative P wave in leads I and aVL suggests a left atrial origin.

•A positive P wave in leads I and aVL suggests a right atrial origin.

With faster baseline heart rates, the abnormal P wave may be hidden within the preceding T wave, producing a "peaked" or "camel hump" type of T wave. If this is not apparent to the interpreting clinician, the PAC may be mistaken for a JPB. (See "ECG tutorial: Atrial and atrioventricular nodal (supraventricular) arrhythmias", section on 'Premature atrial complex'.)

●PR interval – The PR interval may be normal, short, or long. The AV nodal conduction time and, therefore, the PR interval, differs depending on the input pathway to the AV node. PACs that originate from the left atrium typically have shorter conduction times than those originating from the right atrium [47].

●QRS after PAC – The PAC may or may not be conducted via the AV node to the ventricles. Thus, a PAC may be followed by (waveform 3):

•A conducted normal QRS complex.

•A conducted but aberrant (widened) QRS complex. In general, right bundle branch block (RBBB) aberrancy is more common than left bundle branch block (LBBB) aberrancy because of the longer refractory period of the right bundle branch [48].

•No QRS complex (nonconducted PAC) (waveform 4). A nonconducted PAC, especially one that may be obscured by the T wave, may be mistaken for a sinus pause or sinoatrial exit block. Evaluation of multiple leads may be required to detect the PAC, since it may cause a discernible deflection, seen as a deformity of the normal T wave, in only one or a few ECG leads. (See "Sinoatrial nodal pause, arrest, and exit block".)

●Noncompensatory pause – A noncompensatory pause follows a PAC due to resetting of the sinus node by the PAC, with the subsequent sinus beat occurring slightly earlier than would be expected in sinus rhythm (less than twice the sinus P-P interval) (waveform 2). This contrasts with the fully compensatory pause observed after a PVC. Rarely, one may encounter interpolated PACs without a compensatory pause [49].

●Ashman Phenomenon – The Ashman phenomenon is identified when a long R-R interval is followed by a short R-R interval (noncompensatory pause) terminated by an aberrant (wide) QRS complex, often with a right bundle branch block (RBBB) morphology (although it is occasionally an LBBB morphology). Identification of this phenomenon aids in differentiating PACs from PVCs. The long-short sequence of PACs followed by aberrant intraventricular conduction often resembles that of PVCs [50,51].

The Ashman phenomenon reflects physiologic resetting of the sinus node. Aberrant ventricular conduction is a physiologic response to short coupling intervals reflecting relative refractoriness within components of the conduction system [52].

ECG findings with JPBs — The diagnosis of a JPB is made when there is a premature QRS with a PR interval <90 ms, no discernable P wave, or a retrograde P wave in the terminal portion of the QRS or after the QRS.

JPBs have a variety of manifestations on the surface ECG.

●JPBs are most often detected when there is a premature beat with a normal QRS complex and one of the following:

•A P wave with a PR interval that is too short to be considered to be conducted through the AV node (waveform 5). Although the upper limits of the conduction times (PR interval) consistent with JPBs have not been defined, a premature complex with a PR interval less than 90 ms is unlikely to reflect a conducted PAC.

•No P wave. The absence of a P wave may be due to burial of the wave within the QRS complex or the lack of retrograde atrial activation.

•A P wave that occurs at the terminal portion of the QRS complex, within the ST segment, or on the T wave, depending upon the rate of retrograde conduction.

The location of the P wave relative to the QRS complex provides no definitive information regarding the site of origin within the AV junction; it is simply a manifestation of the relative anterograde and retrograde conduction velocities.

●Like PACs, JPBs may conduct anterogradely with a functional or rate-related bundle branch block. In this setting, they may be indistinguishable on the ECG from PVCs. In this setting, only intracardiac recording of His bundle activation will differentiate between these two possibilities. (See "Invasive diagnostic cardiac electrophysiology studies".)

●JPBs may also conduct retrogradely to the atrium and demonstrate conduction block to the ventricles. In this setting, they are similar to PACs and are indistinguishable from nonconducted PACs on the surface ECG.

Ambulatory monitoring — Patients with palpitations or other symptoms suggesting PACs or JPBs, but an unrevealing physical examination and 12-lead ECG, should undergo ambulatory monitoring. In evaluating patients with suspected PACs or JPBs, 24 to 48 hours of ambulatory ECG monitoring significantly increases the likelihood of making the diagnosis, given the sporadic nature of PACs or JPBs in most patients. 24-hour Holter monitoring is also the most widely accepted approach to quantifying the frequency of PACs or JPBs as a percentage of total heart beats. (See "Ambulatory ECG monitoring", section on 'Indications'.)

Differential diagnosis — As discussed above, the differential diagnosis of PACs includes other causes of premature beats, including JPBs (when no preceding ectopic atrial activity is discerned) and PVCs (when no preceding ectopic atrial activity is discerned and there is a wide QRS). (See 'ECG findings with PACs' above.)

Similarly, the differential diagnosis of JPBs includes PACs (when preceding ectopic atrial activity is identified) and PVCs (when there is a wide QRS) (see 'ECG findings with JPBs' above). Also, concealed JPBs may be confused with AV block, as discussed below. (See 'EP testing' below.)

ADDITIONAL EVALUATION

Cardiovascular risk assessment — Since cardiovascular risk is increased in patient populations with PACs (see 'Prognosis' below), evaluation for primary and secondary prevention of CVD is a key component of caring for individuals with PACs. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults" and "Overview of primary prevention of cardiovascular disease in adults" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention)".)

Additional cardiac testing for selected patients — Asymptomatic patients with rare or occasional PACs or JPBs with no symptoms or signs of heart disease on history and physical examination generally require no further evaluation aside from assessing PAC precipitants and adhering to general recommendations for adults for cardiovascular risk assessment. (See 'General management' below.)

For patients with symptoms or signs of heart disease or with symptomatic or frequent PACs (or JPBs), additional evaluation should focus on assessing PAC precipitants and cardiovascular risk (see 'General management' below) and identifying any associated structural heart disease with the following tests:

●24-hour ambulatory (Holter) monitor to quantify the frequency of PACs and determine if they are monomorphic or multimorphic.

●Echocardiography to assess cardiac structure and function.

●Further cardiac testing (eg, stress testing) is indicated only when the clinical presentation and the above initial evaluation identifies evidence of significant cardiac abnormalities (eg, ischemic heart disease, cardiomyopathy, or valve disease) that require further evaluation.

EP testing — Invasive electrophysiology (EP) testing is not required to evaluate PACs.

When PACs occur in a patient undergoing EP study for another reason, EP findings include an atrial activation sequence that is different from the sinus activation sequence, and normal conduction through the AV node and His-Purkinje system (waveform 6). Additionally, functional bundle branch block may be seen, leading to His-ventricular interval prolongation. Nonconducted PACs typically demonstrate block at the AV node. (See "Invasive diagnostic cardiac electrophysiology studies".)

Invasive EP testing is not generally required to evaluate JPBs unless there is a question of infra-His conduction disease, as in the patient with "pseudo AV block" (caused by concealed junctional or His extrasystoles), which should be distinguished from Mobitz II second-degree AV block. (See "Second-degree atrioventricular block: Mobitz type II".)

TREATMENT

General management — Management for all patients with PACs or JPBs (with or without symptoms) includes:

●Identification and avoidance of precipitants – Precipitants may include smoking, alcohol consumption, hypokalemia, hypomagnesemia, and hypoxia.

As noted above, although avoiding caffeine consumption may not decrease the frequency of PACs, abstaining from caffeine may decrease symptoms associated with PACs. (See 'PACs' above.)

●Assessment and management of cardiovascular risk factors – Since patients with PACs are at increased cardiovascular risk, primary and secondary prevention of CVD is a key component of the care of these patients. (See "Overview of primary prevention of cardiovascular disease in adults" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention)".)

Additional management — Further management of PACs or JPBs is based on the whether there are symptoms and/or concurrent heart disease.

●If asymptomatic – For patients with asymptomatic PACs or JPBs, no drug therapy is indicated to treat the arrhythmia.

●If symptomatic

•Initial management – For patients with symptomatic PACs or JPBs, simple reassurance regarding the benign nature of PACs (along with avoidance of precipitants, as described above (see 'General management' above)) is frequently adequate to alleviate symptoms.

•For persistent symptoms – For patients with persistent symptomatic PACs despite efforts to minimize PAC precipitants, we suggest treatment with a beta blocker. We generally treat with oral metoprolol 25 mg orally twice daily as tolerated by blood pressure and resting heart rate. If symptoms are not controlled by metoprolol, an alternative is a nondihydropyridine calcium channel blocker (eg, diltiazem extended release 120 mg orally once daily).

There are few direct data to guide the choice of medical therapies, with most of the available data derived from case reports or small case series. Beta blockers or calcium channel blockers can reduce the symptoms related to PACs and may reduce their frequency, particularly if they are due to enhanced automaticity related to enhanced sympathetic output. Beta blockers or calcium channel blockers do not generally suppress PACs but may be useful in alleviating symptoms by reducing the enhanced inotropy seen with the post-extrasystolic beat (ie, post-extrasystolic potentiation). The response to drug therapy is inconsistent and variable, with some patients having complete or near complete symptom resolution and others showing minimal benefit.

An observational cohort study examined whether beta blockers at low doses were associated with long-term outcomes in individuals with PACs, stratified into high-burden (≥100 PACs/24 h) and low-burden (<100 PACs/24 h) subcohorts [53]. The cohort included individuals with CVD (hypertension, heart failure, and coronary artery disease). In the high-burden subcohort, after propensity score matching, the treatment group (n = 208) had significantly lower mortality rates during mean follow-up of approximately three years than the nontreatment group (n = 832; hazard ratio [HR] 0.52, 95% CI 0.294-0.923), but rates of new stroke and of new AF were similar in the two groups. Similarly, in the low-burden subcohort, the group receiving beta blockers (n = 614) had a 40 percent lower mortality (HR 0.60, 95% CI 0.396-0.913) compared with the nontreatment group (n = 1228), but rates of new stroke and new AF were similar in the two groups. These findings suggest that beta blockers may decrease the mortality rate in patients with high or low burden of PACs, but this effect was not related to the risk of new stroke or new AF. Since the study population included patients with heart failure and coronary artery disease, the reduction in mortality might be related to treatment of these conditions.

We generally do not use type IA, type IC, or type III antiarrhythmic agents (table 1) to treat PACs. These agents can diminish the frequency of PACs in the symptomatic patient and may also suppress PACs that precipitate or trigger other supraventricular arrhythmias including AF, atrial flutter, AV nodal reentrant tachycardia, or AV reentrant tachycardia. Although controlled studies have not been performed with many of these agents, several reports describe their successful use [54-56]. However, the PAC-suppressing effects of these agents must be balanced against the risk of proarrhythmia and other side effects associated with their use. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations", section on 'Proarrhythmia' and "Major side effects of class I antiarrhythmic drugs".)

Catheter ablation — Catheter ablation does not play a role in the vast majority of patients with PACs or JPBs. Catheter ablation is rarely performed for selected patients with frequent PACs or JPBs refractory to medical management in the following settings:

●Frequent symptomatic PACs or JPBs. (See "Overview of catheter ablation of cardiac arrhythmias".)

●A high burden of PACs or JPBs causing (or at risk for causing) arrhythmia-induced cardiomyopathy. (See "Arrhythmia-induced cardiomyopathy", section on 'Frequent atrial ectopy'.)

●To prevent recurrent AF triggered by frequent PACs. The role of catheter ablation to treat AF is discussed separately. (See "Atrial fibrillation: Catheter ablation".)

PACs arising from the pulmonary veins may be treated by pulmonary vein isolation. PACs of non-pulmonary vein origin may also be managed by ablation guided by electroanatomic mapping techniques [57-60]. Successful pulmonary vein isolation procedures in patients with paroxysmal AF and high trigger burden (approximately 500 PACs/h) not only reduce the trigger burden but also increase the PAC coupling interval, suggesting that shorter coupled PACs originate preferentially from the pulmonary veins, which has been considered a reflection of the pulmonary veins' abbreviated refractoriness in patients with AF [61-63]. The procedure for catheter ablation for PACs is the same as for catheter ablation for AF, as discussed separately. (See "Atrial fibrillation: Catheter ablation" and "Catheter ablation for the treatment of atrial fibrillation: Periprocedural issues".)

PROGNOSIS — 

Frequent PACs in populations of adults without known CVD (other than hypertension) is associated with an increased risk of cardiovascular morbidity, cardiovascular mortality, and all-cause mortality.

Cardiovascular mortality — Frequent PACs are associated with elevated risk of cardiovascular mortality, as illustrated by the following studies [64-68]:

●Among 7692 adults (mean age 52.5 years) with no history of MI, stroke, AF, or atrial flutter enrolled in the prospective NIPPON DATA 90 cohort and followed for an average of 14 years, only 64 persons (0.8 percent) had one or more PACs on a screening 12-lead ECG at enrollment [66]. Study participants were considered generally healthy, although over 20 percent had hypertension. The presence of PACs was an independent predictor for cardiovascular deaths (hazard ratio [HR] 2.03, 95% CI 1.12-3.66). The association between PACs and cardiovascular death was stronger among participants with hypertension.

●Among 7504 adults without known CVD (other than hypertension) in an NHANES study cohort who were followed for up to 18 years, 89 persons (1.2 percent) had one or more PACs on a screening 12-lead ECG [67]. In a multivariate analysis adjusted for demographics, clinical variables, and ECG measures, the presence of PACs (but not PVCs) was associated with higher risk of all-cause mortality (HR 1.41, 95% CI 1.08-1.80), cardiovascular mortality (HR 1.78, 95% CI 1.26-2.44), and ischemic heart disease mortality (HR 2.40, 95% CI 1.59-3.47).

●Among 5371 consecutive patients without AF or a permanent pacemaker (PPM) at baseline who underwent 24-hour Holter monitoring in Taiwan, a PAC burden >76 beats per day was an independent predictor of mortality (HR 1.4, 95% CI 1.2-1.6), cardiovascular hospitalization (HR 1.3; 95% CI 1.1-1.5), new-onset AF (HR 1.8, 95% CI 1.4-2.2), and PPM implantation (HR 2.8, 95% CI 1.9-4.2) over a mean follow-up of 10 years [68].

●A cohort study examined the distribution of PAC burden and its relationship to all-cause mortality and cardiovascular death in 15,893 persons who underwent Holter monitoring [69]. Multivariate analysis found that PAC burden was associated with risk of all-cause mortality (4^th versus 1^st quartile, adjusted HR 1.67) and cardiovascular death (HR 1.12 per PAC increase).

AF — PACs are a well-established trigger of AF [11,70,71]. (See "Mechanisms of atrial fibrillation", section on 'Role of premature atrial complex and other arrhythmia triggers'.)

Numerous studies have found that frequent PACs are associated with later detection of AF as well as adverse cardiovascular events [64,65,68,72-80].

●A meta-analysis included 33 studies with a total of 198,876 patients with mean age of 52 to 76 years [81]. Identification of frequent PACs on Holter was associated with later detection of AF (HR 2.96, 95% CI 2.33-3.76; 15 study cohorts, n = 16,613), first stroke (HR 2.54, 95% CI 1.66-3.83; three cohorts, n = 1468) and all-cause mortality (HR 2.14, 95% CI 1.94–2.37; six cohorts, n = 7571).

●In the STROKESTOP I mass-screening study for AF in 75- and 76-year-old persons in Sweden, over a median follow-up of 4.2 years, of the 6100 participants, 15 percent (n = 894) had arrhythmia, with frequent PACs being the most common (11.6 percent; n = 709) and irregular supraventricular tachycardias being more common than regular [82]. Persons with the most AF-similar supraventricular tachycardias, irregular and lacking p waves (1.6 percent; n = 97), had the highest risk of developing AF (HR 4.3) and an increased risk of death (HR 2.0). Thus, progression of atrial arrhythmias from PACs to more AF-like episodes was associated with development of AF, suggesting a possible role for screening for AF in individuals with frequent supraventricular activity.

●Higher burden of PACs is a predictor of subclinical AF in patients with cryptogenic stroke [77] (See "Cryptogenic stroke and embolic stroke of undetermined source (ESUS)".)

●Among patients who have undergone catheter ablation for AF, the presence of frequent PACs is a predictor of AF recurrence [78,83]. (See "Atrial fibrillation: Catheter ablation".)

●In a study of 1559 patients without obstructive coronary artery disease who underwent exercise testing, the presence of PACs during exercise testing was an independent predictor of development of AF during the next four years (adjusted HR 2.5, 95% CI 1.76-3.57) [84].

●When PACs are frequent and associated with cardiovascular risk factors, the long-term risk of AF is higher, especially when there are signs of left atrial disease. In such cases, high N-terminal pro-B-type natriuretic peptide levels presage the occurrence of AF [85].

Stroke — The above-cited meta-analysis identified an association between frequent PACs and increased risk of subsequent first stroke [81]. As discussed above, the causes of stroke in patients with PACs include thromboembolism from the left atrium caused by AF and/or atrial myopathy. (See 'Clinical conditions and medications' above.)

Excessive PAC activity (defined as ectopic supraventricular beats ≥480/day, atrial runs of 10 to 29 s, or both) in the acute phase of an ischemic stroke has been linked with AF detection during 24-month follow-up and thus may be a marker to select patients for prolonged ECG monitoring [86].

Since excessive PAC burden is associated with increased risk of ischemic stroke in adults without known AF, a potential role for anticoagulation for individuals with excessive PACs has been postulated [13], but the efficacy and safety of this approach has not been established.

Kidney function — A retrospective cohort study of 10,981 patients found that high daily PAC burden identified on Holter monitor recordings was linked with an elevated (adjusted HR 1.24, 95% CI 1.03-1.50) risk of major adverse kidney events (defined as an estimated glomerular filtration rate [eGFR] decline of 40 percent, eGFR <15 mL/min/1.73 m², or the initiation of hemodialysis) [87].

Lack of relation to sudden cardiac death — Isolated PACs are not associated with risk of sudden cardiac death (SCD). Among 14,574 patients in the ARIC study who had a 12-lead ECG and a two-minute three-lead rhythm strip at baseline, there was no significant increase in the risk of SCD among persons with PACs (HR 1.15, 95% CI 0.56-2.39), although when PACs occurred concurrently with PVCs, the risk of SCD was higher (HR 6.39 compared with patients with neither PACs nor PVCs, 95% CI 2.58-15.84) [88].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Catheter ablation of arrhythmias" and "Society guideline links: Supraventricular arrhythmias".)

SUMMARY AND RECOMMENDATIONS

●Definition – Supraventricular premature beats (SPBs) include premature atrial contractions (PACs) and junctional premature beats (JPBs) arising from the atrioventricular (AV) node. (See 'Introduction' above.)

●Prevalence – PACs are nearly ubiquitous, occurring commonly in adults with and without heart disease. JPBs occur much less commonly than both PACs and premature ventricular complexes (PVCs). (See 'Prevalence' above.)

●Symptoms and signs – PACs and JPBs are asymptomatic in the vast majority of patients but can cause symptoms such as a sensation of "skipping" or palpitations. The most characteristic physical examination finding is an irregular pulse. (See 'Clinical manifestations' above.)

●Diagnosis – The diagnostic evaluation of patients with suspected PACs (or JPBs) should focus on documenting their presence or absence with an ECG or ambulatory cardiac monitoring.

•PACs – These are observed on the surface ECG as a P wave that occurs earlier than the anticipated next sinus P wave and has a different morphology (eg, inverted or biphasic) from the sinus P wave (waveform 1 and waveform 3 and waveform 4 and waveform 2). Every lead should be examined, as subtle differences in morphology may be present. Often the PR interval is different from that during sinus rhythm. (See 'ECG findings with PACs' above.)

•JPBs – These are observed on the ECG as a QRS complex with no preceding P wave or with a P wave occurring too soon before the QRS to be considered to be conducted through the AV node (waveform 5). (See 'ECG findings with JPBs' above.)

●Additional cardiac testing – Additional cardiac testing with a 24-hour ambulatory (Holter monitor) and echocardiography is generally reserved for patients with symptoms or signs of heart disease or symptomatic or frequent PACs (or JPBs). (See 'Additional cardiac testing for selected patients' above.)

●General management – Management for all patients with PACs or JPBs includes identification and avoidance of precipitants (eg, alcohol and smoking tobacco) and assessment and management of cardiovascular risk factors. (See 'General management' above and "Overview of primary prevention of cardiovascular disease in adults" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention)".)

●Additional management – In persons with frequent PACs or JPBs, management is based on the presence or absence of symptoms and/or underlying structural heart disease. (See 'Additional management' above.)

•Asymptomatic PACs or JPBs – No drug therapy is indicated to treat asymptomatic PACs or JPBs.

•Symptomatic PACs or JPBs – For patients with symptomatic PACs or JPBs, reassurance regarding the benign nature of PACs is frequently adequate to alleviate symptoms (along with avoidance of precipitants).

For patients with persistent symptomatic PACs or JPBs despite efforts to minimize potential PAC precipitants, we suggest treatment with a beta blocker or nondihydropyridine calcium channel blocker (eg, diltiazem or verapamil) (Grade 2C). We generally treat with oral metoprolol 25 mg twice daily. (See 'Additional management' above.)

●Catheter ablation – Catheter ablation does not play a role in the vast majority of patients with PACs or JPBs. It is rarely performed for selected patients with frequent PACs or JPBs refractory to medical management with frequent symptomatic PACs or JPBs, high burden of PACs or JPBs causing arrhythmia-induced cardiomyopathy, or high burden of PACs causing atrial fibrillation (AF). (See 'Catheter ablation' above.)

●Prognosis – Frequent PACs are associated with increased risk of AF, cardiovascular mortality, and all-cause mortality. (See 'Prognosis' above.)

ACKNOWLEDGMENTS — 

The UpToDate editorial staff acknowledges Philip Podrid, MD, FACC, and Bernard Gersh, MB, ChB, DPhil, FRCP, MACC, who contributed to earlier versions of this topic review.