Arrhythmias in COPD

INTRODUCTION — The natural history of chronic obstructive pulmonary disease (COPD) includes gradually worsening shortness of breath and functional limitation, caused by a progressive decline in lung function and the development of co-morbid illnesses [1]. Multifocal atrial tachycardia, atrial fibrillation, and ventricular arrhythmias are common co-morbidities among patients with COPD [2].

The potential contributing factors, occurrence rates, and management of arrhythmias in patients with COPD will be discussed here. The management of stable COPD and atrial and ventricular arrhythmia is reviewed separately. (See "Stable COPD: Initial pharmacologic management" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis, and evaluation" and "Multifocal atrial tachycardia" and "Management of atrial fibrillation: Rhythm control versus rate control" and "Wide QRS complex tachycardias: Approach to the diagnosis" and "Wide QRS complex tachycardias: Approach to management" and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".)

POTENTIAL CONTRIBUTING FACTORS — Multiple factors have been evaluated as possible contributors to the development of arrhythmias in patients with COPD [3,4]. Some are related to comorbid disease processes with shared risk factors and others are more specifically related to COPD. Factors related to COPD that have been studied regarding their potential role in arrhythmia development are discussed in greater detail below.

Comorbid disease processes — COPD shares risk factors (eg, age, smoking) with a number of disease processes and related treatments that are also associated with cardiac arrhythmias, including [3,4]:

●Coronary heart disease

●Hypertensive heart disease

●Right and/or left ventricular failure

●Hypokalemia and hypomagnesemia

These comorbid disease processes are discussed separately in the topics about the individual arrhythmias. (See "Multifocal atrial tachycardia", section on 'Prevalence' and "Left ventricular hypertrophy and arrhythmia".)

Hypoxemia and respiratory acidosis — Hypoxemia and respiratory acidosis have been identified in case series as factors associated with the development of arrhythmias among patients with COPD [3,4]. The exact mechanisms by which hypoxemia and acidosis provoke arrhythmias are unclear. One possible explanation comes from the observation that norepinephrine levels (compared with normal values) were elevated in hypercapnic, hypoxemic patients with COPD who were hospitalized with fluid retention and peripheral edema [5]. It is hypothesized that the low arterial blood pressure caused by hypercapnia contributed to the elevation in norepinephrine. The catecholamine activation may in turn contribute to development of arrhythmias in such patients.

Theophylline — Though less commonly used in contemporary COPD management, theophylline has numerous well-characterized cardiac effects, including a dose-dependent increase in heart rate, enhancement of atrial automaticity, and acceleration of intracardiac conduction. Theophylline is also associated with rhythm disturbances, such as sinus tachycardia, premature atrial complex (PAC; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat), supraventricular tachycardia, atrial fibrillation, unifocal and multifocal atrial tachycardia, and ventricular arrhythmias. (See "Management of refractory chronic obstructive pulmonary disease", section on 'Theophylline, monitored by drug levels'.)

The frequency of atrial and ventricular arrhythmias increases with the serum theophylline level, as illustrated in these studies:

●In a cross-sectional, retrospective study of 100 patients, the heart rate was directly related to the serum theophylline concentration, and the serum theophylline concentration was the strongest independent predictor of arrhythmia [6]. Patients with a serum concentration of theophylline (10 to 20 mcg/mL [56 to 111 micromol/L]) had an odds ratio for arrhythmia of 3.7, when compared with those patients who had serum theophylline levels of less than 2.5 mcg/mL. Multifocal atrial tachycardia (MAT) was found in 8 percent of patients with a serum theophylline concentration of 10 to 20 mcg/mL compared with 16 percent of those with values greater than 20 mcg/mL.

●One study prospectively evaluated arrhythmias among 16 patients with theophylline toxicity (a serum theophylline concentration exceeding 30 mcg/mL) [7]. Sinus tachycardia and ventricular premature beats (VPBs) were the most common arrhythmias, occurring in 85 percent and 80 percent of subjects, respectively. The frequency and complexity of ventricular ectopy were largely influenced by the theophylline concentration and by coexistent conditions, such as underlying ischemic heart disease and age. Potentially life-threatening arrhythmias were rare (one patient had ventricular tachycardia), and only one patient required intervention with antiarrhythmic therapy.

However, the magnitude of the effect of low therapeutic doses of theophylline on the occurrence of arrhythmias is unclear, and the current target trough serum level is lower (5 to 12 mcg/mL [28 to 67 micromol/L]) than the range used in earlier studies (10 to 20 mcg/mL [56 to 111 micromol/L]) [6,8].

Beta-adrenergic agonists — Inhaled beta-2 adrenergic agonists are a mainstay of therapy for COPD, but have the potential to increase heart rate and may increase cardiac arrhythmias via nonselective beta-adrenergic effects [9]. However, a number of studies support the overall safety of inhaled selective beta-2 adrenergic agonists.

The effect of nebulized albuterol on sinus and atrioventricular (AV) node activity was examined in a study of 18 patients with asthma or mild COPD [10]. Nebulized albuterol (5 mg) shortened the sinus cycle length and sinus node recovery time. In addition, administration of albuterol enhanced the AV nodal conduction, reduced AV nodal refractory time, and decreased myocardial refractory time.

Despite the effect of albuterol on sinus and AV nodal conduction noted above, clinical studies suggest that inhaled selective beta-adrenergic agonists infrequently cause serious arrhythmias. A meta-analysis of 33 randomized trials of patients receiving beta-agonists for obstructive airways disease revealed that beta-adrenergic agonists were associated with an increased risk of sinus tachycardia (RR 3.06, 95% CI 1.7-5.5), but were not associated with a significantly increased risk of major adverse cardiovascular events (composite endpoint of ventricular tachycardia, atrial fibrillation, syncope, heart failure, myocardial infarction, cardiac arrest, and sudden death) [11]. A single inhaled dose of beta-agonist increased the heart rate (mean 9 beats per minute, 95% CI 5.32-12.92). The effect of high-dose albuterol for COPD exacerbations was not addressed in this study.

The effect of long-acting beta-agonists (LABA) on heart rate and development of arrhythmia has also been examined. An analysis of the data from two trials examining the effect of LABAs on heart rate and cardiac arrhythmias found a slight increase in atrial tachycardias, but no increase in mean heart rate or risk of serious arrhythmias [12,13]. A third trial of 1429 patients with COPD found that administration of a LABA (arformoterol or salmeterol) did not result in a statistically significant increase of atrial arrhythmias [12]. The role of LABAs in the management of COPD is discussed separately. (See "Stable COPD: Initial pharmacologic management", section on 'Long-acting beta-agonists'.)

Cigarette smoking — Whether cigarette smoke exposure increases the risk of arrhythmias, independent of the degree of airflow obstruction, is unclear. It is hypothesized that active cigarette smoking may increase the risk of arrhythmias, due to profibrotic effects of nicotine on myocardial tissue or an increased susceptibility to catecholamines, but this has not been definitively demonstrated [14]. (See "Supraventricular premature beats", section on 'Etiology'.)

Cardiac autonomic dysfunction — Alterations of cardiac autonomic function may be important in the development of arrhythmia in patients with COPD. Some patients with COPD lack the normal pattern of cardiac circadian rhythm changes and some have a prolonged QT interval [15,16]. An absence of the normal nocturnal decrease in sympathetic tone among patients with COPD is suggested by 24-hour ambulatory electrocardiographic (ECG) recordings that do not reveal the typical nocturnal slowing of the heart rate. It has been suggested that this altered circadian pattern may predispose to arrhythmia [15].

Ventricular diastolic dysfunction and respiratory failure — The presence of arrhythmias in COPD has been associated with concurrent left ventricular diastolic dysfunction. In a series of 22 patients with COPD, diastolic dysfunction was the only clinical variable predictive of ventricular premature beats [17]. Among patients with COPD, ventricular diastolic dysfunction may be related to right ventricular overload from pulmonary hypertension or to common causes such as increased age or comorbid myocardial ischemia or systemic hypertension. (See "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis" and "Pathophysiology of heart failure with preserved ejection fraction".)

Respiratory failure may also contribute to the risk of arrhythmias. In the preceding study of diastolic dysfunction in COPD, PAC correlated with hypoxemia and hypercarbia [17]. Furthermore, the number of arrhythmias significantly decreased when the respiratory failure improved.

Exercise — Exercise does not appear to increase the risk of serious arrhythmias in patients with severe COPD [18,19]. In a case series of 122 patients with severe COPD, for example, ventricular arrhythmias (eg, VPBs ≥6/min, bigeminy, multiform VPBs, couplets, or nonsustained ventricular tachycardia [VT]) developed during exercise in 12 percent [19]. None of these required specific treatment. Half of the patients who had ventricular arrhythmias during exercise had similar or lower grade ventricular arrhythmias at rest prior to testing. Patients without a history of ischemic heart disease or without any evidence of a cardiac arrhythmia at rest have a low likelihood of developing serious arrhythmias during exercise [19].

OCCURRENCE OF ARRHYTHMIAS IN PATIENTS WITH COPD — The incidence and prevalence of atrial and ventricular arrhythmias among patients with COPD varies widely among reported studies [12,20-22]. This variation may be due to differences in the study populations (eg, severity of COPD, presence of respiratory failure), the presence or absence of ventricular failure or underlying cardiac disease, the methodology used to record the arrhythmias (a single electrocardiogram [ECG] versus a continuous 24-hour recording), and the medications used in management of COPD (eg, theophylline, beta-adrenergic agonists).

Holter monitoring in stable COPD — Cardiac arrhythmias, both supraventricular and ventricular, are significantly more common among patients with COPD compared to those without, with a prevalence that varies according to the severity of underlying COPD [3,12,23]. As examples:

●Among a cohort of 7441 patients (mean age 64 years, 49 percent female) who underwent clinically indicated pulmonary function testing as well as 24-hour Holter monitoring between 2000 and 2009, 3121 patients (41.9 percent) were diagnosed with COPD [23]. Patients diagnosed with COPD were significantly more likely to have atrial fibrillation/atrial flutter (23 versus 11 percent), nonsustained ventricular tachycardia (13 versus 6 percent), or sustained ventricular tachycardia (1.6 versus 0.9 percent), than those without COPD.

●In a cohort of 69 hypoxemic patients with severe but stable COPD who underwent continuous ECG recordings, episodes of supraventricular tachycardia occurred in 69 percent, while atrial fibrillation was the underlying rhythm in 7 percent [3]. Premature ventricular beats (primarily multiform) and nonsustained ventricular tachycardia were present in 83 percent and 22 percent, respectively.

Specific arrhythmias associated with COPD — Multifocal atrial tachycardia (MAT), atrial fibrillation, and ventricular arrhythmias often complicate the course of COPD, particularly during acute exacerbations [3].

Multifocal atrial tachycardia — MAT is defined by the following electrocardiographic findings (waveform 1) [24,25]:

●Discrete P waves with at least three different morphologies

●Atrial rate faster than 100 beats per minute

●Separation of the P waves by isoelectric intervals

●Variable P-P intervals, P-R duration, and R-R intervals

The evaluation and diagnosis of MAT are discussed separately. (See "Multifocal atrial tachycardia", section on 'Clinical manifestations and diagnosis'.)

In patients with COPD, MAT most commonly develops in the setting of an acute exacerbation, but is also associated with certain drugs (eg, theophylline), other pulmonary processes (eg, pneumonia, pulmonary embolism, hypoxemia), and nonpulmonary disorders such as hypokalemia, hypomagnesemia, and chronic renal failure [25]. (See "Multifocal atrial tachycardia", section on 'Associated clinical conditions'.)

Among patients with chronic airway obstruction who were admitted to the hospital with acute respiratory failure, MAT was noted in 17 percent [26]. However, this report may be an overestimate of the frequency of MAT as concomitant medications were not reported, and the study was performed in an era when theophylline and nonselective beta-agonists were widely used. In a systematic review that examined the contribution of COPD to the development of MAT, COPD was present in 55 percent of patients with MAT, making it the most common pulmonary disorder associated with MAT [25].

The rapid ventricular response in MAT likely contributes to the respiratory impairment in patients with COPD, either by elevation of the left ventricular diastolic pressure or by limiting the portion of the cardiac cycle spent in diastole [27]. This increase in left ventricular pressure can contribute to pulmonary hypertension, potentially increasing right atrial pressure in addition to increasing left atrial pressure and augmenting the stimulus for MAT.

Atrial fibrillation — Atrial fibrillation is characterized by an irregularly irregular rhythm and the absence of distinct P waves on the ECG and can be a cause of worsening dyspnea and hypoxemia among patients with COPD. The diagnosis of atrial fibrillation and the evaluation of predisposing conditions are discussed separately. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation" and "Epidemiology, risk factors, and prevention of atrial fibrillation" and "Atrial fibrillation and flutter after cardiac surgery".)

The prevalence of atrial fibrillation appears to be increasing among patients admitted with a COPD exacerbation. Analysis of data from the Nationwide Inpatient Sample (a publicly available all-payer United States database) between 2003 and 2014 identified 1,345,270 oxygen-dependent patients admitted with COPD exacerbation [28]. The prevalence of atrial fibrillation exceeded 21 percent of study patients in 2014, compared with 12.9 percent in 2003. Patients with concurrent atrial fibrillation were at significantly higher risk of death, respiratory failure, and need for assisted ventilation among other comorbidities.

The likelihood of developing new atrial fibrillation in patients with COPD is higher than patients without lung disease. Among subjects in the Copenhagen City Heart Study who met spirometric criteria for COPD, the incidence of new onset atrial fibrillation was 0.9 percent over five years of follow up compared with 0.4 percent among those with normal spirometry [20]. In several series of ambulatory patients with COPD, the risk of developing atrial fibrillation increased as the forced expiratory volume in one second (FEV₁) decreased [20,29,30]. In addition, atrial fibrillation is associated with higher symptom burden, worse quality of life, and worse cardiovascular outcomes among patients with COPD than those without [31].

Atrial fibrillation is also increased during and after acute exacerbations of COPD. Among 152 patients hospitalized with an exacerbation of COPD, 24 hour Holter monitoring revealed permanent or paroxysmal atrial fibrillation in 30 and 12 percent, respectively [22]. In a separate series of 944 patients with atrial fibrillation following an acute exacerbation of COPD, the rate of atrial fibrillation was significantly higher within the first 90 days following COPD exacerbation compared with the reference period of 90 days preceding COPD exacerbation (14.1 versus 7.3 per 100 person-months, rate ratio 1.9; 95% CI 1.6-2.3) [32].

Ventricular arrhythmias — Ventricular arrhythmias, ranging from isolated ventricular premature beats (VPBs) to nonsustained ventricular tachycardia, are often noted on 24 hour ECG monitoring of patients with COPD [21-23,33]. The evaluation and diagnosis of ventricular tachycardia are discussed separately. (See "Wide QRS complex tachycardias: Approach to the diagnosis" and "Nonsustained VT in the absence of apparent structural heart disease".)

The frequency of ventricular arrhythmias among patients with COPD has been examined in several studies:

●In a series of 6351 consecutive patients with COPD who underwent Holter monitoring and pulmonary function testing, ventricular tachycardia (VT) was almost twice as likely to occur among those with COPD than without (23 versus 13 percent); COPD and VT remained independently associated after adjusting for left ventricular ejection fraction, demographics, and other comorbidities [21].

●In a case control study, PVCs were more common among outpatients with COPD than controls (924 +/- 493 beats versus 35 +/- 23 beats); nonsustained ventricular tachycardia was noted in 8 patients (27 percent) with COPD, but none of the controls [33].

TREATMENT

General measures — When managing arrhythmias in patients with COPD, treatment measures are tailored to the specific type and severity of the arrhythmia and the unique clinical characteristics of each patient. Certain general measures are useful in the majority of patients, including:

●Optimization of COPD management – Optimal management of COPD includes providing supplemental oxygen (aiming for a pulse oxygen saturation of 90 to 94 percent), reversing bronchoconstriction, and treating hypercapnia with bronchodilation and respiratory support. Selective, short-acting beta-adrenergic agents are a key therapy for exacerbations of COPD and should be titrated to provide adequate bronchodilation and relief of dyspnea without excess cardiac chronotropic effects. (See "Stable COPD: Initial pharmacologic management" and "COPD exacerbations: Management", section on 'Oxygen therapy' and "COPD exacerbations: Management", section on 'Home/office short-acting bronchodilator treatments'.)

●Correction of precipitating conditions – Acute myocardial ischemia, and electrolyte, acid-base, and metabolic abnormalities, particularly hypokalemia and hypomagnesemia, should be identified and treated. (See "Multifocal atrial tachycardia", section on 'Magnesium and potassium repletion' and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Triggers'.)

●Avoidance of the concurrent use of drugs that can prolong the QT interval – Drugs that can prolong the QT interval include clarithromycin, ketoconazole, and certain psychotropic medications (table 1). QT prolongation can initiate ventricular tachycardias, particularly torsade de pointes [34]. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".)

●Cautious dosing or discontinuation of theophylline – For patients on chronic theophylline therapy, maintain the serum level at 8 to 12 mcg/mL (44 to 67 micromol/L), since 85 percent of its beneficial effect occurs at a level of 12 mcg/mL or less, and theophylline may be arrhythmogenic even at levels previously considered within the therapeutic range (10 to 20 mcg/mL or 56 to 111 micromol/L) [35]. (See 'Theophylline' above and "Management of refractory chronic obstructive pulmonary disease", section on 'Theophylline, monitored by drug levels'.)

Multifocal atrial tachycardia — Specific antiarrhythmic therapy is indicated for multifocal atrial tachycardia (MAT) when the rapid ventricular response produces or worsens ischemia, heart failure, or peripheral perfusion. The general management of multifocal atrial tachycardia is discussed in detail separately. (See "Multifocal atrial tachycardia", section on 'Treatment'.)

When pharmacologic intervention is indicated for MAT, the preferred agents are verapamil and metoprolol (table 2). Due to the potential risk of bronchoconstriction from beta-blocking agents, verapamil is most commonly used as the initial agent in patients with COPD. Metoprolol is reserved for use when verapamil does not provide adequate rate control. The dosing and administration of verapamil and metoprolol are presented in the table (table 2) and are discussed separately. (See "Multifocal atrial tachycardia", section on 'Pharmacologic therapy'.)

When administering verapamil to patients with COPD, we continuously monitor pulse oximetry and provide supplemental oxygen, aiming for a pulse oxygen saturation of 90 to 94 percent. Theoretically, calcium channel blockers may lower the partial pressure of arterial oxygen in patients with lung disease due to the relief of hypoxic vasoconstriction in pulmonary arteries/arterioles supplying poorly ventilated areas. This possibility was supported by pooled data from several studies that found a mean reduction in arterial oxygen tension from 105 to 78 mmHg after the administration of a calcium channel blocker, a change that may be clinically significant [36]. (See "COPD exacerbations: Management", section on 'Oxygen therapy'.)

Despite concerns about beta-blockers triggering bronchoconstriction in patients with COPD, a systematic review found that the beta-1 selective agent metoprolol resulted in a decrease in ventricular response of 24 to 40 percent among the four studies described (45 patients) without exacerbating respiratory symptoms [25]. A separate systematic review did not find evidence of adverse respiratory effects with short-term use of cardioselective beta-blockers in patients with COPD who did not have active wheezing or bronchoconstriction [37]. For patients with COPD that is not characterized by a bronchospastic component, cautious use of metoprolol is a reasonable option, when verapamil is ineffective. (See "Major side effects of beta blockers", section on 'Increased airways resistance'.)

Verapamil is generally used in preference to diltiazem for MAT due to the limited supportive data for diltiazem, although success was reported with an initial bolus and maintenance infusion in a case series [25].

Atrial fibrillation and supraventricular tachyarrhythmias — The American College of Cardiology/American Heart Association and European Society of Cardiology have published recommendations for the management of atrial fibrillation in patients with pulmonary disease (table 3) [38-40].

●Urgent electrical cardioversion of supraventricular tachyarrhythmias is indicated if hemodynamic collapse, angina, or heart failure is present. For patients who have not been anticoagulated or have suboptimal anticoagulation, a transesophageal echocardiogram is frequently performed to exclude intracardiac thrombus just prior to cardioversion. (See "Overview of the acute management of tachyarrhythmias".)

Pharmacologic therapy to terminate the arrhythmia or control the ventricular response is indicated if these maneuvers are unsuccessful (table 3). The management of atrial fibrillation and other supraventricular tachyarrhythmias is discussed separately. (See "Overview of the acute management of tachyarrhythmias" and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".)

Intravenous flecainide (not available as an intravenous preparation in the United States) is an alternative therapy for restoring normal sinus rhythm in patients with COPD and atrial fibrillation [39]. Flecainide should be avoided in patients with underlying left heart failure or myocardial ischemia. (See "Atrial fibrillation: Cardioversion", section on 'Specific antiarrhythmic drugs'.)

●Antithrombotic therapy is initiated in patients with atrial fibrillation based on standard practices, although anticoagulation has not been studied specifically in patients with atrial fibrillation in the setting of chronic lung disease. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".)

●The majority of patients presenting with atrial fibrillation will require slowing of the ventricular rate to improve symptoms. Nondihydropyridine calcium channel blockers (eg, verapamil, diltiazem) have generally been the preferred pharmacologic therapy for new onset atrial fibrillation in patients with COPD, as these agents have a weak bronchodilator effect, rather than the potential bronchoconstrictive effect of noncardioselective beta blockers (table 3) [38,39]. However, beta blockers are generally more effective at achieving adequate ventricular rate control and retrospective data from a nationwide database suggest that beta blockers might actually be safer than calcium channel blockers [41,42]. While the retrospective database study did not find an increase in mortality with nonselective beta blockers among patients with COPD [42], the use of cardioselective beta blockers is preferred. Doses of nondihydropyridine calcium channel blockers and the beta blocker metoprolol are provided in the table (table 3).

Digoxin offers no advantages over calcium channel blockers for patients with atrial fibrillation and COPD, except in the presence of heart failure, and some data suggest a higher mortality in patients treated with digoxin monotherapy (table 3) [38,42].

●Several effective antiarrhythmic drugs must be used with caution or not at all in patients with COPD [38,39]:

•Beta blockers are contraindicated in patients with uncontrolled bronchospasm and wheezing. Similar considerations apply to propafenone, a Class IC antiarrhythmic (table 4), and sotalol, a class III agent, which have beta-blocking properties.

•Because of the overlap of many risk factors between COPD and coronary heart disease and the frequent co-existence of these two processes, Class IA and IC antiarrhythmic drugs (table 4) should be used with caution as these drugs are contraindicated in patients with coronary heart disease.

•Adenosine, which has a rapid onset of action and an effect that is blocked by theophylline, may provoke bronchospasm and must be used with caution in patients with COPD [24].

•Chronic amiodarone therapy may cause pulmonary toxicity. Although initial reports suggested a 5 to 15 percent incidence, the incidence appears to be lower (1 to 5 percent) with lower maintenance doses used in contemporary practice, although pulmonary toxicity has been reported with low cumulative doses. In patients with preexisting lung disease such as COPD, chronic therapy should be used with caution or avoided given the potential risk of superimposed lung toxicity in those with limited respiratory reserve [43]. (See "Amiodarone pulmonary toxicity" and "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".)

●Society guidelines suggest avoiding beta-adrenergic agonists in patients with atrial fibrillation based on low quality evidence [38]. We make the decision regarding use of beta-adrenergic agonists on a case-by-case basis. For patients with difficulty achieving rate control but without active bronchoconstriction, it is reasonable to avoid or minimize the dose of beta agonists. On the other hand, for patients with dyspnea and uncontrolled bronchoconstriction, treatment with beta-2 selective adrenergic agonists is appropriate and generally well-tolerated.

●We generally avoid initiation of theophylline in patients with atrial fibrillation, particularly if rate control has been problematic [38]. For patients with new onset atrial fibrillation in the setting of chronic theophylline therapy, we ensure that the dose of theophylline is in the low therapeutic range (8 to 12 mcg/mL [44 to 67 micromol/L]) or discontinue it if it is not felt to be vital to the treatment of the patient’s COPD.

Symptomatic ventricular arrhythmias — Symptomatic ventricular arrhythmias require prompt treatment. Electrical cardioversion should immediately be performed if hemodynamic collapse, myocardial ischemia, or ventricular failure is present. (See "Cardioversion for specific arrhythmias" and "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".)

Pharmacologic treatment is indicated for the symptomatic patient who is not hemodynamically compromised. The pharmacologic therapy of ventricular arrhythmias is discussed separately, but some caveats regarding treatment in patients with COPD are discussed below. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy" and "Wide QRS complex tachycardias: Approach to management".)

When managing patients with COPD and ventricular arrhythmias, it is important to consider potential adverse effects of antiarrhythmic medications on lung function.

●Amiodarone is the most commonly used agent for ventricular arrhythmias. While patients with COPD are not necessarily at higher risk of amiodarone pulmonary toxicity, they may be at higher risk for respiratory failure if toxicity occurs [24]. (See "Amiodarone pulmonary toxicity".)

●Sotalol has a significant nonselective beta-blocking effect, which can trigger bronchospasm, and thus is usually avoided in patients with COPD and active bronchoconstriction. (See "Clinical uses of sotalol", section on 'Major side effects'.)

●Mexiletine is another alternative but is of variable efficacy and interacts with theophylline via CYP1A2 inhibition.

An implantable cardioverter-defibrillator (ICD) may be indicated for long-term management of patients with clinically significant (symptomatic and/or sustained) ventricular arrhythmias. In a case-control study of patients with COPD and a left ventricular ejection fraction of 35 percent or less, patients with an ICD had a lower total mortality (odds ratio 0.18, 95% CI 0.06–0.56) [44]. A discussion of the indications for ICD placement is provided separately. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)

Asymptomatic ventricular arrhythmias — The optimal management of asymptomatic ventricular arrhythmias in patients with COPD is not known. Approximately 4 percent of patients with COPD experience sudden or unexplained death; however, the role of serious ventricular arrhythmias in these deaths is poorly defined [45].

The benefit of treating asymptomatic ventricular arrhythmias in an attempt to lessen the risk of sudden death in these patients also remains unproven. Antiarrhythmic drugs may actually increase risk of arrhythmias, worsen heart failure, and cause lung injury [24,46]. Thus, considerable caution should be exercised in administering antiarrhythmic drugs to asymptomatic patients with COPD and ventricular arrhythmias. Given the potential risks, we avoid pharmacologic antiarrhythmic therapy in these patients. (See "Nonsustained ventricular tachycardia: Clinical manifestations, evaluation, and management", section on 'Treatment'.)

PROGNOSIS — The effect of arrhythmias on the prognosis of patients with COPD is dependent on the clinical setting (eg, severity of COPD exacerbation), presence of comorbidities (eg, shock, heart failure, stroke, renal insufficiency), and the specific arrhythmia [47-49]. Among 69 ambulatory patients monitored as part of the nocturnal oxygen therapy trial, the presence of asymptomatic ventricular arrhythmias was not a predictor of death [3]. In contrast, among patients hospitalized with an exacerbation of COPD, the development of multifocal atrial tachycardia (MAT) was associated with increased mortality with one series reporting an in-hospital mortality of 46 percent [24]. MAT and other serious atrial arrhythmias can be associated with malignant ventricular arrhythmias in patients with acute respiratory failure [50].

In an observational cohort study of 1013 patients with severe exacerbations of COPD, arrhythmias were a risk factor for mortality (odds ratio 2.70, 95% CI 1.40–5.22) [48].

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: Chronic obstructive pulmonary disease".)

SUMMARY AND RECOMMENDATIONS

●Incidence – Both supraventricular and ventricular arrhythmias are common among patients with chronic obstructive pulmonary disease (COPD). The risk is further elevated during periods of acute exacerbation and thoracic surgery. (See 'Introduction' above and 'Occurrence of arrhythmias in patients with COPD' above.)

●Risk factors – Multiple factors contribute to the development of arrhythmias in patients with COPD, including hypoxemia, respiratory acidosis, electrolyte disturbances, medications, systemic hypertension, cardiac autonomic dysfunction, coronary heart disease, and heart failure. (See 'Potential contributing factors' above.)

●Common arrhythmias in patients with COPD

•Multifocal atrial tachycardia (MAT) – Characteristic features of MAT include discrete P waves with at least three different morphologies, an atrial rate faster than 100 beats/min, isoelectric intervals separating the P waves, and variability in the P-P intervals, P-R duration, and R-R intervals. MAT most commonly develops in the setting of an acute exacerbation of COPD. (See 'Multifocal atrial tachycardia' above and "Multifocal atrial tachycardia".)

•Atrial fibrillation – Atrial fibrillation is characterized by an irregularly irregular rhythm and the absence of distinct P waves. New onset of atrial fibrillation is associated with advancing COPD but may also lead to increasing dyspnea and hypoxemia. (See 'Atrial fibrillation' above and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".)

•Ventricular arrhythmias – Ventricular tachyarrhythmias, ranging from isolated premature ventricular contractions (PVCs) to nonsustained ventricular tachycardia, are common in ambulatory and hospitalized patients with COPD. It appears unlikely that asymptomatic ventricular arrhythmias adversely impact mortality among ambulatory patients with COPD. (See 'Ventricular arrhythmias' above and 'Prognosis' above.)

●General measures, regardless of arrhythmia type

•Metabolic and electrolyte disturbances – The treatment of arrhythmias in patients with COPD begins with correction of hypoxemia, respiratory acidosis, electrolyte abnormalities (eg, hypokalemia, hypomagnesemia), and cardiac ischemia. (See 'General measures' above.)

•Management of COPD medications – Medications that can prolong the QT interval should be avoided and arrhythmogenic drugs such as theophylline should be decreased in dose or discontinued. Short-acting selective beta-2 adrenergic agents should be titrated to provide adequate bronchodilation and relief of dyspnea without excess cardiac chronotropic effects. (See 'Treatment' above.)

●Management of MAT – For patients with MAT in the setting of an exacerbation of COPD, the main treatment is directed toward reversing bronchoconstriction and improving gas exchange. Pharmacologic therapy for MAT is indicated when a rapid ventricular response produces or worsens cardiac or peripheral ischemia heart failure or hypoxemia. For most patients with COPD and symptomatic MAT, we suggest using verapamil rather than metoprolol (Grade 2C); metoprolol may be used as add-on therapy if necessary in those without active bronchoconstriction (table 2). (See "Multifocal atrial tachycardia", section on 'Pharmacologic therapy'.)

●Management of atrial fibrillation and atrial flutter

•In those with shock, angina, or heart failure – Urgent electrical cardioversion of atrial fibrillation or atrial flutter is indicated if hemodynamic collapse, angina, or heart failure is present. (See 'Atrial fibrillation and supraventricular tachyarrhythmias' above.)

•Pharmacologic rate control, for those without shock, angina, or heart failure – For stable patients with atrial fibrillation or flutter and COPD, we suggest using verapamil or diltiazem rather than metoprolol for rate control (Grade 2C). Metoprolol is reserved for patients without uncontrolled bronchoconstriction who do not respond to the calcium channel blockers. For those with an accessory pathway or heart failure, amiodarone or digoxin are preferred (table 3). (See 'Atrial fibrillation and supraventricular tachyarrhythmias' above and "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".)

•Antithrombotic therapy – For patients with atrial fibrillation, antithrombotic therapy is initiated based on standard practices. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".)

•Antiarrhythmic therapy – Several drugs that are effective antiarrhythmics (eg, sotalol, adenosine, amiodarone, mexiletine) must be used with caution or avoided in patients with COPD. (See 'Atrial fibrillation and supraventricular tachyarrhythmias' above and 'Symptomatic ventricular arrhythmias' above.)

●Management of ventricular arrhythmias

•Symptomatic ventricular arrhythmias – Urgent treatment with either cardioversion (in unstable patients) or antiarrhythmics (in those without instability) is required for symptomatic ventricular arrhythmias. (See 'Symptomatic ventricular arrhythmias' above and "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".)

•Asymptomatic ventricular arrhythmias – For patients with COPD and asymptomatic ventricular arrhythmias, we avoid antiarrhythmic therapy due to uncertain benefit and the potential for a proarrhythmic effect. (See 'General measures' above and 'Asymptomatic ventricular arrhythmias' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to earlier versions of this topic review.