Arrhythmias in COPD - UpToDate

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Arritmias na DPOC
AUTORES: Omar A Minai, MD, Christopher Madias, MD
EDITOR DE SEÇÃO: Umur Hatipoglu, MD, MBA
EDITORES ADJUNTOS: Paul Dieffenbach, MD, Susan B Yeon, MD, JD, FACC
Todos os tópicos são atualizados à medida que novas evidências são disponibilizadas e nosso processo de revisão por
pares é concluído.
Revisão da literatura atualizada até: julho de 2023.

Última atualização deste tópico: 19 de junho de 2023.
INTRODUÇÃO
A história natural da doença pulmonar obstrutiva crônica (DPOC) inclui piora gradual da falta
de ar e limitação funcional, causada por um declínio progressivo na função pulmonar e pelo
desenvolvimento de doenças comórbidas [1 ] . Taquicardia atrial multifocal, fibrilação atrial e
arritmias ventriculares são comorbidades comuns entre pacientes com DPOC [ 2 ].
Os potenciais fatores contribuintes, taxas de ocorrência e manejo de arritmias em pacientes

com DPOC serão discutidos aqui. O manejo da DPOC estável e da arritmia atrial e ventricular
é revisado separadamente. (Consulte "DPOC estável: manejo farmacológico inicial" e
"Taquicardias de complexo QRS estreito: manifestações clínicas, diagnóstico e avaliação" e
"Taquicardia atrial multifocal" e "Tratamento de fibrilação atrial: controle de ritmo versus
controle de frequência" e "Taquicardias de complexo QRS largo : Abordagem ao diagnóstico"
e "Taquicardias do complexo QRS largo: Abordagem ao manejo" e "Fibrilação atrial: Visão
geral e tratamento da fibrilação atrial de início recente" .)
FATORES POTENCIAIS DE CONTRIBUIÇÃO
Vários fatores foram avaliados como possíveis contribuintes para o desenvolvimento de

arritmias em pacientes com DPOC [ 3,4 ]. Alguns estão relacionados com processos de
doenças comórbidas com factores de risco partilhados e outros estão mais especificamente
relacionados com a DPOC. Os fatores relacionados à DPOC que foram estudados quanto ao
seu papel potencial no desenvolvimento de arritmia são discutidos com mais detalhes
abaixo.
https://www.uptodate.com/contents/arrhythmias-in-copd/print?search=dpoc&source=search_result&selectedTitle=24~150&usage_type=default&display_rank… 1/30
Processos de doenças comórbidas – A DPOC compartilha fatores de risco (por exemplo,
idade, tabagismo) com uma série de processos de doenças e tratamentos relacionados que
também estão associados a arritmias cardíacas, incluindo [3,4 ] :
● Doença coronariana
● Doença cardíaca hipertensiva
● Insuficiência ventricular direita e/ou esquerda
● Hipocalemia e hipomagnesemia
Esses processos de doenças comórbidas são discutidos separadamente nos tópicos sobre
arritmias individuais. (Consulte "Taquicardia atrial multifocal", seção 'Prevalência' e
"Hipertrofia e arritmia ventricular esquerda" .)
Hipoxemia e acidose respiratória — Hipoxemia e acidose respiratória foram identificadas

em séries de casos como fatores associados ao desenvolvimento de arritmias em pacientes
com DPOC [ 3,4 ]. Os mecanismos exatos pelos quais a hipoxemia e a acidose provocam
arritmias não são claros. Uma possível explicação vem da observação de que os níveis de
noradrenalina (em comparação com os valores normais) estavam elevados em pacientes
hipercápnicos e hipoxêmicos com DPOC que foram hospitalizados com retenção de líquidos
e edema periférico [5 ] . Supõe-se que a baixa pressão arterial causada pela hipercapnia
contribuiu para a elevação da norepinefrina. A ativação das catecolaminas pode, por sua vez,
contribuir para o desenvolvimento de arritmias nesses pacientes.
Teofilina — Embora menos comumente usada no tratamento contemporâneo da DPOC, a

teofilina tem numerosos efeitos cardíacos bem caracterizados, incluindo um aumento
dependente da dose na frequência cardíaca, aumento da automaticidade atrial e aceleração
da condução intracardíaca. A teofilina também está associada a distúrbios do ritmo, como
taquicardia sinusal, complexo atrial prematuro (PAC; também referido como batimento atrial
prematuro, complexo supraventricular prematuro ou batimento supraventricular
prematuro), taquicardia supraventricular, fibrilação atrial, taquicardia atrial unifocal e
multifocal e arritmias ventriculares. (Consulte "Manejo da doença pulmonar obstrutiva
crônica refratária", seção sobre 'Teofilina, monitorada pelos níveis do medicamento' .)
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 'Beta adrenergic agonists'.)
● 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.
Use of UpToDate is subject to the Terms of Use.
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44. Razak E, Kamireddy S, Saba S. Implantable cardioverter-defibrillators confer survival
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UPLIFT® COPD trial: findings and recommendations. Respir Med 2012; 106:515.
46. Pratt CM. Asymptomatic ventricular arrhythmias in patients with obstructive lung
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47. Steer J, Gibson GJ, Bourke SC. Predicting outcomes following hospitalization for acute
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48. Ongel EA, Karakurt Z, Salturk C, et al. How do COPD comorbidities affect ICU outcomes?
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COPD exacerbations. COPD 2011; 8:354.
Topic 1454 Version 46.0
GRAPHICS
Eletrocardiograma taquicardia atrial multifocal de derivação única
Características clínicas:
Pacientes idosos
Descompensação de doença pulmonar
Pós-operatório
Arritmia geralmente não causa comprometimento hemodinâmico grave
High mortality
ECG features:
P waves have ≥3 forms
Atrial rate is usually 100 to 200 bpm
Atrial rate is irregular
PR interval varies
Isoelectric baseline between P waves
May progress to atrial fibrillation
ECG: electrocardiogram; bpm: beats per minute.
Courtesy of Alfred Buxton, MD.
Graphic 127222 Version 1.0
Some reported causes and potentiators of the long QT syndrome
Congenital
Jervell and Lange-Nielsen syndrome (including "channelopathies")

Romano-Ward syndrome
Idiopathic
Acquired
Metabolic disorders Other factors Androgen deprivation therapy
Hypokalemia Myocardial GnRH agonist/antagonist therapy
Hypomagnesemia ischemia or Bilateral surgical orchiectomy
Hypocalcemia infarction,
Diuretic therapy via electrolyte disorders
especially with
Starvation particularly hypokalemia and
prominent T-wave
Anorexia nervosa hypomagnesemia
inversions
Liquid protein diets Herbs
Intracranial
Hypothyroidism disease Cinchona (contains quinine), iboga
Bradyarrhythmias HIV infection (ibogaine), licorice extract in overuse
Sinus node via electrolyte disturbances
Hypothermia
dysfunction Toxic exposure:
AV block: Second or Organophosphate
third degree insecticides
Medications*
High risk
Adagrasib Cisaparide Lenvatinib Selpercatinib

Ajmaline ¶ (restricted Levoketoconazole Sertindole ¶
Amiodarone Δ availability) Methadone Sotalol
Arsenic trioxide Delamanid ¶ Mobocertinib Terfenadine ◊
Astemizole ◊ Disopyramide Δ Papavirine Vandetanib
Bedaquline Dofetilide (intracoronary) Vernakalant ¶
Bepridil ◊ Dronedarone Procainamide Ziprasidone
Chlorpromazine Haloperidol (IV) Quinidine
Ibutilide Quinine
Ivosidenib
Moderate risk
Amisulpride ¶ (oral) § Droperidol Inotuzumab Propafenone

Azithromycin Encorafenib ozogamacin Propofol
Capecitabine Entrectinib Isoflurane Quetiapine
Carbetocin ¶ Erythromycin Levetiracetam Quizartinib
Certinib Escitalopram Levofloxacin Ribociclib
Chloroquine Etelcalcetide (systemic) Risperidone
Citalopram Fexinidazole Lofexidine Saquinavir
Clarithromycin Flecainide Meglumine Sevoflurane

Clofazimine Floxuridine antimoniate Sparfloxacin ¶
Clomipramine ¥ Fluconazole Midostaurin Sunitinib
Clozapine Fluorouracil Moxifloxacin Tegafur ¶
Crizotinib (systemic) Nilotinib Terbutaline
Dabrafenib Flupentixol ¶ Olanzapine Thioridazine
Dasatinib Gabobenate Ondansetrol (IV > Toremifene
Deslurane dimeglumine oral) Vemurafenib
Domperidone ¶ Gemifloxacin ¶ Osimertinib Voriconazole
Doxepin ¥ Gilteritinib Oxytocin
Doxifluridine ¶ Halofantrine Pazopanib

Haloperidol (oral) Pentamidine
Imipramine ¥ Pilsicainide ◊
Pimozide
Piperaquine
Probucol ◊
Low risk ‡
Albuterol Fingolimod Mequitazine Ranolazine

Alfuzosin Fluoxetine Methotrimeprazine (due to
Amisulpride (IV) § Fluphenazine Metoclopramide bradycardia)
Amitriptyline ¥ Formoterol (rare reports) Relugolix
Anagrelide Foscarnet Metronidazole Rilpivirine
Apomorphine Fostemsavir (systemic) Romidepsin
Arformoterol Gadofosveset Mifepristone Roxithromycin
Artemether- Glasdegib Mirtazapine Salmeterol

lumefantrine Goserelin Mizolastine Sertraline
Asenapine Granisetron Nelfinavir Siponimod
Atomoxetine Hydroxychloroquine Norfloxacin Solifenacin
Benperidol (rare reports) Nortriptyline ¥ Sorafenib
Bilastine ¶ Hydroxyzine Ofloxacin Sulpiride
Bosutinib Iloperidone (systemic) Tacrolimus
Bromperidol Indacaterol Olodaterol (systemic)
Buprenorphine † Itraconazole Osilodrostat Tamoxifen
Buserelin Ketoconazole Oxaliplatin Telavancin
Ciprofloxacin (systemic) Ozanimod ΔΔ Telithromycin

(Systemic) Lacidipine Pacritinib Teneligliptin
Cocaine (Topical) Lapatinib Paliperidone Tetrabenazine
Degarelix Lefamulin Panobinostat Trazodone
Desipramine ¥ Leuprolide Pasireotide Triclabendazole
Deutetrabenazine Leuprolide- Pefloxacin Triptorelin
Dexmedetomidine** norethindrone Periciazine ¶ Tropisetron ¶
Dolasetron Levalbuterol Pimavanserin Vardenafil
Donepezil Levomethadone Pipamperone Vilanterol
Lithium Pitolisant Vinflunine
Efavirenz Loperamide ¶¶ in Ponesimod Voclosporin

Eliglustat overdose Primaquine Vorinostat
Eribulin Lopinavir Promazine Zuclopenthixol
Ezogabine Macimorelin Radotinib
Mefloquine
This is not a complete list of all corrected QT interval (QTc)-prolonging drugs and does not include
drugs with either a minor degree or isolated association(s) with QTc prolongation that appear to
be safe in most patients but may need to be avoided in patients with congenital long QT
syndrome depending upon clinical circumstances. A more complete list of such drugs is available
at the CredibleMeds website. For clinical use and precautions related to medications and drug
interactions, refer to the UpToDate topic review of acquired long QT syndrome discussion of
medications and the Lexicomp drug interactions tool.
AV: atrioventricular; IV: intravenous; QTc: rate-corrected QT interval on the electrocardiogram.
* Classifications provided by Lexicomp according to US Food & Drug Administration guidance:

Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythic Potential for Non-
Antiarrhythmic Drugs – Questions and Answers; Guidance for Industry US Food and Drug
Administration, June 2017 (revision 2) available at:
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
CM073161.pdf as updated August 8, 2023 (https://www.fda.gov/media/170814/download) with
additional data from CredibleMeds QT drugs list [1,2] . The use of other classification criteria may
lead to some agents being classified differently by other sources.
¶ Not available in the United States.
Δ In contrast with other class III antiarrhythmic drugs, amiodarone is rarely associated with
torsades de pointes; refer to accompanying text within UpToDate topic reviews of acquired long
QT syndrome.
◊ Withdrawn from market in most countries due to adverse cardiovascular effects.
§ IV amisulpride antiemetic use is associated with less QTc prolongation than the higher doses
administered orally as an antipsychotic.
¥ Some other cyclic antidepressants (ie, amoxapine, maprotiline, protriptyline, trimipramine) may
also prolong the QT interval, but data are insufficient to identify level of risk with confidence;
refer to UpToDate content on cyclic antidepressant pharmacology, administration, and side
effects.
‡ The "low risk" category includes drugs with limited evidence of clinically significant QTc
prolongation or TdP risk; many of these drugs have label warnings regarding possible QTc effects
or recommendations to avoid use or increase ECG monitoring when combined with other QTc
prolonging drugs.
† Rarely associated with significant QTc prolongation at usual doses for treatment of opioid use
disorder, making buprenorphine a suitable alternative for patients with methadone-associated
QTc prolongation. Refer to UpToDate clinical topic reviews.
** The United States FDA labeling for the sublingual preparation of dexmedetomidine warns
against use in patients at elevated risk for QTc prolongation. Both intravenous (ie, sedative) and
sublingual formulations of dexmedetomidine have a low risk of QTc prolongation and have not
been implicated in TdP.
¶¶ Over-the-counter; available without a prescription.
ΔΔ Not associated with significant QTc prolongation in healthy persons. Refer to UpToDate clinical
topic for potential adverse cardiovascular (CV) effects in patients with CV disease.
Data from:
1. Lexicomp Online. Copyright ©1978-2023 Lexicomp, Inc. All Rights Reserved.
2. CredibleMeds QT drugs list website sponsored by Science Foundation of the University of Arizona. Available at
http://crediblemeds.org/.
Pharmacologic agents for acute heart rate control in patients with

multifocal atrial tachycardia and chronic obstructive pulmonary disease
Initial Subsequent Maintenance

Drug Onset Side effects
dose doses dose
Verapamil* ¶ ◊ 5 to 10 1 to 2 10 mg IV 120 to 480 mg Hypotension, heart

mg IV minutes bolus over 2 daily block, heart failure
over 2 minutes
minutes given 15 to 30
minutes after
initial dose
Metoprolol Δ ¶ ◊ 2.5 to 5 5 2.5 to 5 mg IV Long-acting: Hypotension, heart

mg IV minutes over 2 to 5 block, bradycardia,
50 mg orally
over 2 to minutes at 10- heart failure,
once daily
5 minute bronchoconstriction
minutes intervals up to Short-acting:
a maximum of 25 mg orally
15 mg IV twice daily
MAT: multifocal atrial tachycardia; COPD: chronic obstructive pulmonary disease.
* For all patients with COPD and MAT and a rapid ventricular response, correction of hypoxemia,
acidosis, and other metabolic disturbances is recommended. Theophylline can increase the
ventricular response, so dosing should be regulated to keep the serum level in the range of 8 to
12 mg/mL; discontinuation of the medication should be considered.
¶ Verapamil is preferred over metoprolol for heart rate control of MAT in patients with COPD due
to concerns about exacerbating bronchoconstriction.
Δ Representative of the type of selective beta-1 blockers that could be used, but similar drugs
could be given in appropriate doses.
◊ Verapamil and beta blockers should not be given to patients with sinus node dysfunction or
preexisting second- or third-degree block unless a temporary or permanent pacemaker has been
implanted. Verapamil and beta blockers should be administered cautiously in patients with
decompensated heart failure or hypotension to avoid worsening these conditions.
Intravenous pharmacologic agents for acute heart rate control in

patients with atrial fibrillation and chronic obstructive pulmonary
disease*
Maintenance
dose (for Major side
Drug Loading dose Onset
initial 24 to effects
72 hours)
There is evidence and/or general agreement that the following drugs are effective for
acute heart rate control in patients with AF who do NOT have an accessory pathway or
heart failure
Verapamil ¶ 0.075 to 0.15 mg/kg 3 to 5 Hypotension, heart

(usually 5 to 10 minutes block, heart failure
mg/dose [maximum 10
mg]) IV over 2 to 3
minutes, may repeat
dose in 15 to 30
minutes if inadequate
response to initial dose
Diltiazem ¶ 0.25 mg/kg IV (average 2 to 7 5 to 15 mg/hour Hypotension, heart

adult dose 20 mg) over minutes IV infusion block, heart failure
2 minutes, may repeat titrated
with a higher dose according to
of 0.35 mg/kg IV ventricular heart
(average adult dose 25 rate
mg) in 15 to 30 minutes
if inadequate response
to initial dose
Metoprolol ¶ Δ ◊ 2.5 to 5 mg IV over 2 5 Hypotension, heart

minutes; up to 3 doses minutes block, bradycardia,
(maximum 15 mg total) heart failure,
administered 5 to 10 bronchoconstriction
minutes apart may be
given
For acute heart rate control in patients with AF and an accessory pathway
Amiodarone ¶ § 150 mg IV over 30 1 to 30 0.5 mg/minute Hypotension, sinus

minutes, followed by 1 minutes IV infusion for bradycardia, heart
mg/minute IV infusion up to additional block, QT
for 6 hours, followed by 48 hours prolongation,
0.5 mg/minute IV ventricular
infusion for 18 hours arrhythmias,
pulmonary toxicity
For acute heart rate control in patients with AF and heart failure but not an accessory
pathway
Digoxin ¶ ¥ ‡ 0.25 mg IV every 2 15 to 30 0.125 to 0.25 mg Digitalis toxicity,

hours, up to a total minutes, orally once a day heart block,
dose of 1.5 mg peak bradycardia
effect in
1 to 5
hours
Amiodarone ¶ § 150 mg IV over 30 1 to 30 0.5 mg/minute Hypotension, sinus

minutes, followed by 1 minutes IV infusion for bradycardia, heart
mg/minute IV infusion up to additional block, QT
for 6 hours, followed by 48 hours prolongation,
0.5 mg/minute IV ventricular
infusion for 18 hours arrhythmias,
pulmonary toxicity
* For patients with hemodynamic instability due to atrial fibrillation, direct current cardioversion
is the treatment of choice. For all patients with COPD and atrial fibrillation with a rapid ventricular
response, correction of hypoxemia, acidosis, and other metabolic disturbances is recommended.
Theophylline can increase the ventricular response, so dosing should be regulated to keep the
serum level in the range of 8 to 12 mg/mL; discontinuation of the medication should be
considered.
¶ Electrocardiographic (ECG or telemetry) and blood pressure monitoring should be continuously

performed during initial loading dose and frequently (eg, every 4 hours) during maintenance
intravenous dosing.
◊ Representative of the type of selective beta-1 blockers that could be used but similar drugs
could be given in appropriate doses.
Δ Nondihydropyridine calcium channel antagonists (eg, verapamil, diltiazem) are preferred over
metoprolol for heart rate control of atrial fibrillation in patients with COPD due to concerns about
exacerbating bronchoconstriction.
§ Amiodarone can be useful when other measures are unsuccessful or contraindicated. For
patients with an accessory pathway, intravenous amiodarone can be given if the rhythm cannot
be converted or ablated and rate control is needed.
¥ There is evidence and/or general agreement that digoxin is effective in patients with heart
failure but not an accessory pathway.
‡ Dosing shown is for normal renal function and normal body weight. Reduced doses are needed
for renal insufficiency or low body weight. Refer to topic on "Method of digitalization".
Revised (2018) Vaughan Williams classification of antiarrhythmic drugs

abridged table
Class 0 (HCN channel blockers)
Ivabradine
Class I (voltage-gated Na+ channel blockers)

Class Ia (intermediate dissociation):
Quinidine, ajmaline, disopyramide, procainamide
Class Ib (rapid dissociation):
Lidocaine, mexilitine
Class Ic (slow dissociation):
Propafenone, flecainide
Class Id (late current):
Ranolazine
Class II (autonomic inhibitors and activators)

Class IIa (beta blockers):
Nonselective: carvedilol, propranolol, nadolol
Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol
Class IIb (nonselective beta agonists):
Isoproterenol
Class IIc (muscarinic M2 receptor inhibitors):
Atropine, anisodamine, hyoscine, scopolamine
Class IId (muscarinic M2 receptor activators):
Carbachol, pilocarpine, methacholine, digoxin
Class IIe (adenosine A1 receptor activators):
Adenosine
Class III (K+ channel blockers and openers)

Class IIIa (voltage dependent K+ channel blockers):
Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant
Class IIIb (metabolically dependent K+ channel openers):
Nicorandil, pinacidil
Class IV (Ca++ handling modulators)

Class IVa (surface membrane Ca++ channel blockers):
Bepridil, diltiazem, verapamil
Classe IVb (bloqueadores dos canais intracelulares de Ca++):
Flecainida, propafenona
Classe V (bloqueadores de canais mecanossensíveis):
Nenhum medicamento aprovado
Classe VI (bloqueadores de canais de junções comunicantes)
Nenhum medicamento aprovado
Classe VII (moduladores alvo upstream)
Inibidores da enzima conversora de angiotensina
Bloqueadores dos receptores da angiotensina
Ácidos gordurosos de omega-3
Estatinas
HCN: controlado por nucleotídeo cíclico ativado por hiperpolarização; Na: sódio; K: potássio; Ca:
cálcio.
Gráfico 120433 Versão 3.0
Contributor Disclosures
Omar A Minai, MD No relevant financial relationship(s) with ineligible companies to
disclose. Christopher Madias, MD No relevant financial relationship(s) with ineligible companies to
disclose. Umur Hatipoglu, MD, MBA No relevant financial relationship(s) with ineligible companies to
disclose. Paul Dieffenbach, MD No relevant financial relationship(s) with ineligible companies to
disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to
disclose.
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30/08/2023, 08:54 Arrhythmias in COPD - UpToDate

Reimpressão oficial do UpToDate ®

Revisão da literatura atualizada até: julho de 2023.

Os potenciais fatores contribuintes, taxas de ocorrência e manejo de arritmias em pacientes

FATORES POTENCIAIS DE CONTRIBUIÇÃO

Vários fatores foram avaliados como possíveis contribuintes para o desenvolvimento de

Hipoxemia e acidose respiratória — Hipoxemia e acidose respiratória foram identificadas

Teofilina — Embora menos comumente usada no tratamento contemporâneo da DPOC, a

found in 8 percent of patients with a serum theophylline concentration of 10 to 20

● One study prospectively evaluated arrhythmias among 16 patients with theophylline

Beta-adrenergic agonists — Inhaled beta-2 adrenergic agonists are a mainstay of therapy

Cigarette smoking — Whether cigarette smoke exposure increases the risk of arrhythmias,

Cardiac autonomic dysfunction — Alterations of cardiac autonomic function may be

Ventricular diastolic dysfunction and respiratory failure — The presence of arrhythmias

OCCURRENCE OF ARRHYTHMIAS IN PATIENTS WITH COPD

Holter monitoring in stable COPD — Cardiac arrhythmias, both supraventricular and

Specific arrhythmias associated with COPD — Multifocal atrial tachycardia (MAT), atrial

Multifocal atrial tachycardia — MAT is defined by the following electrocardiographic

● Discrete P waves with at least three different morphologies

● Separation of the P waves by isoelectric intervals

Atrial fibrillation — Atrial fibrillation is characterized by an irregularly irregular rhythm and

Ventricular arrhythmias — Ventricular arrhythmias, ranging from isolated ventricular

General measures — When managing arrhythmias in patients with COPD, treatment

● Optimization of COPD management – Optimal management of COPD includes

● Correction of precipitating conditions – Acute myocardial ischemia, and electrolyte,

● Cautious dosing or discontinuation of theophylline – For patients on chronic

Multifocal atrial tachycardia — Specific antiarrhythmic therapy is indicated for multifocal

When administering verapamil to patients with COPD, we continuously monitor pulse

Despite concerns about beta-blockers triggering bronchoconstriction in patients with COPD,

Atrial fibrillation and supraventricular tachyarrhythmias — The American College of

● Urgent electrical cardioversion of supraventricular tachyarrhythmias is indicated if

Pharmacologic therapy to terminate the arrhythmia or control the ventricular response

"Overview of the acute management of tachyarrhythmias" and "Atrial fibrillation:

Intravenous flecainide (not available as an intravenous preparation in the United States)

● Antithrombotic therapy is initiated in patients with atrial fibrillation based on standard

• Beta blockers are contraindicated in patients with uncontrolled bronchospasm and

● Society guidelines suggest avoiding beta-adrenergic agonists in patients with atrial

● We generally avoid initiation of theophylline in patients with atrial fibrillation,

Symptomatic ventricular arrhythmias — Symptomatic ventricular arrhythmias require

Pharmacologic treatment is indicated for the symptomatic patient who is not

● Sotalol has a significant nonselective beta-blocking effect, which can trigger

● Mexiletine is another alternative but is of variable efficacy and interacts with

An implantable cardioverter-defibrillator (ICD) may be indicated for long-term management

Asymptomatic ventricular arrhythmias — The optimal management of asymptomatic

In an observational cohort study of 1013 patients with severe exacerbations of COPD,

SOCIETY GUIDELINE LINKS

SUMMARY AND RECOMMENDATIONS

● Incidence – Both supraventricular and ventricular arrhythmias are common among

● Risk factors – Multiple factors contribute to the development of arrhythmias in

● Common arrhythmias in patients with COPD

• Multifocal atrial tachycardia (MAT) – Characteristic features of MAT include

• Atrial fibrillation – Atrial fibrillation is characterized by an irregularly irregular

• Ventricular arrhythmias – Ventricular tachyarrhythmias, ranging from isolated

● General measures, regardless of arrhythmia type

• Metabolic and electrolyte disturbances – The treatment of arrhythmias in patients

• Management of COPD medications – Medications that can prolong the QT interval

● Management of MAT – For patients with MAT in the setting of an exacerbation of

● Management of atrial fibrillation and atrial flutter

• In those with shock, angina, or heart failure – Urgent electrical cardioversion of

• Antithrombotic therapy – For patients with atrial fibrillation, antithrombotic

• Antiarrhythmic therapy – Several drugs that are effective antiarrhythmics (eg,

● Management of ventricular arrhythmias

• Symptomatic ventricular arrhythmias – Urgent treatment with either

• Asymptomatic ventricular arrhythmias – For patients with COPD and