Abstract and Introduction
Chronic obstructive pulmonary disease (COPD) is highly prevalent among patients with atrial fibrillation (AF), shares common risk factors, and adds to the overall morbidity and mortality in this population. Additionally, it may promote AF and impair treatment efficacy. The prevalence of COPD in AF patients is high and is estimated to be ~25%. Diagnosis and treatment of COPD in AF patients requires a close interdisciplinary collaboration between the electrophysiologist/cardiologist and pulmonologist. Differential diagnosis may be challenging, especially in elderly and smoking patients complaining of unspecific symptoms such as dyspnoea and fatigue. Routine evaluation of lung function and determination of natriuretic peptides and echocardiography may be reasonable to detect COPD and heart failure as contributing causes of dyspnoea. Acute exacerbation of COPD transiently increases AF risk due to hypoxia-mediated mechanisms, inflammation, increased use of beta-2 agonists, and autonomic changes. Observational data suggest that COPD promotes AF progression, increases AF recurrence after cardioversion, and reduces the efficacy of catheter-based antiarrhythmic therapy. However, it remains unclear whether treatment of COPD improves AF outcomes and which metric should be used to determine COPD severity and guide treatment in AF patients. Data from non-randomized studies suggest that COPD is associated with increased AF recurrence after electrical cardioversion and catheter ablation. Future prospective cohort studies in AF patients are needed to confirm the relationship between COPD and AF, the benefits of treatment of either COPD or AF in this population, and to clarify the need and cost-effectiveness of routine COPD screening.
Atrial fibrillation (AF) is the most common sustained arrhythmia affecting 33.5 million people globally. Across the developed world, AF increasingly contributes to a rising tide of hospitalization, morbidity and mortality. At the same time, chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease characterized by persistent airflow limitation with a global prevalence of stage 2 COPD or higher of around 10%. Chronic obstructive pulmonary disease is present in up to 23% of AF patients[3–5] and new-onset AF is twice as common in COPD patients compared with patients without COPD.
The association between AF and COPD is not completely understood. Chronic obstructive pulmonary disease and AF share common risk factors contributing to the onset of both diseases. Additionally, COPD might also directly contribute to the onset of AF by COPD-related pathophysiological mechanisms. Correctly diagnosing COPD in AF patients is important because COPD in patients with AF is a negative prognostic factor for progression from paroxysmal AF to persistent AF and the efficacy of AF treatment.[8,9] Additionally, concomitant COPD is associated with increased hospital admissions and all-cause mortality in AF patients.[4,10] Moreover, among patients with AF, COPD is associated with higher symptom burden, worse quality of life, and worse cardiovascular and bleeding outcomes. International professional societies recommend the correction of hypoxaemia and acidosis as initial management for patients who develop AF during an acute pulmonary illness or exacerbation of chronic pulmonary disease.[12,13] However, recommendations concerning when and how to test for COPD and the long-term management of COPD specifically in AF patients remain uncertain.
This review provides an update on the current understanding of how COPD contributes to a unique dynamic arrhythmogenic substrate for AF. Experimental data pointing to possible pathophysiologic mechanisms in AF patients with comorbid COPD as well as diagnostic and therapeutic considerations in AF patients with COPD will be highlighted. Finally, we emphasize the need for larger prospective cohort studies in AF patients to more robustly determine the role of COPD and its treatment in predisposing to incident and recurrent AF and to identify the COPD phenotypes in AF patients.
Atrial Arrhythmogenic Mechanisms in Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease is a chronic pulmonary disease and is characterized by airflow limitations due to small airway disease (obstructive bronchiolitis) and parenchymal destruction (emphysema) leading to expiratory flow limitation and hyperinflation. Hyperinflation is defined as an increase in end-expiratory lung volume and can be seen at rest or during exercise, static and dynamic hyperinflation, respectively. Destruction of the alveoli can result in emphysema, low diffusion capacity, and hypoxaemia.
Several COPD-related mechanisms contributing to AF onset and progression are summarized in Figure 1. Gas exchange abnormalities, such as hypoxaemia and hypercapnia, can lead to pulmonary vasoconstriction and subsequent pulmonary hypertension which may result in right ventricular hypertrophy and diastolic dysfunction. Chronic hypoxaemia modulates the expression of hypoxia-inducible factor 1 and increases systemic inflammation and oxidative stress promoting pro-fibrotic remodelling of the atrial tissue. Long-term advanced COPD is associated with right heart disease. In rats, induced right heart disease produced a substrate for AF maintenance prominently involving right atrial fibrosis, conduction abnormalities, and right atrial re-entrant activity. Additionally, leucocyte elastase-induced COPD in rabbits increased atrial arrhythmogenesis. Sympathetic overactivity has been observed in both hypoxaemic and normoxemic patients with COPD[20,21] and is involved in AF progression. As a result of dynamic hyperinflation, patients with COPD develop intrinsic positive end-expiratory pressure, which increases pulmonary vascular resistance resulting in interventricular septum encroaching on the left ventricle, compromised left ventricular inflow, and left atrial and pulmonary venous pressure rises.[2,6,17,23] Concomitant comorbidities like obesity and systemic arterial hypertension may contribute critically to the structural atrial substrate remodelling process. Cardiovascular disease is one of the most important comorbidities. About 30% of patients with heart failure also have COPD. Obstructive sleep apnoea (OSA) is also frequently seen in patients with COPD, referred to as 'overlap syndrome'. Co-existing COPD may put OSA patients closer to the steep part of the oxyhaemoglobin dissociation curve leading to more excessive downward drifts in oxygen saturation.
Different pathophysiological mechanisms how chronic obstructive pulmonary disease contributes to atrial fibrillation. Ventilation/perfusion (V/Q) mismatch. AF, atrial fibrillation; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 s; V/Q, ventilation/perfusion.
While atrial structural remodelling is important in providing an AF-maintaining substrate in patients with COPD, AF onset, and paroxysms are often temporally related to acute exacerbations of COPD (AECOPD).[26–28] During AECOPD, changes in blood gases as well as transmural pressure gradients due to airflow limitation and dynamic hyperinflation result in pulmonary pressure rises with tricuspid regurgitation which particularly impacts the right atrium. In a sheep model with continuous ventilation under autonomic blockade, the transition from hypercapnia back to normal blood gases, rather than longer hypoxic or hypercapnic episodes, was characterized by increased atrial vulnerability due to a differential recovery of right atrial refractoriness and right atrial conduction properties. Additionally, intrathoracic pressure swings, as occurring during dynamic hyperinflation as well as during obstructive respiratory events, have been shown to transiently shorten right atrial effective refractory period, right atrial action potential duration and increase AF inducibility by parasympathetic mediated mechanisms in a spontaneously breathing pig model.[30,31] These factors may create a dynamic arrhythmogenic substrate which transiently increases AF risk during AECOPD. Additionally, AECOPD and the use of sympathomimetic and parasympatholytic medication may also increase trigger formation by changes in pH and autonomic nervous system activation.
Eur Heart J. 2021;42(5):532-540. © 2021 Oxford University Press
Copyright 2007 European Society of Cardiology. Published by Oxford University Press. All rights reserved.