Review Article

iMedPub Journals Chronic Obstructive Pulmonary Diseases 2016
Vol.1 No.1:2

The Association between Chronic Obstructive Pulmonary Disease (COPD)
and Atrial Fibrillation: A Review
Varun Shah1, Trishla Desai1 and Abhinav Agrawal2,*
1Department of Internal Medicine, University of Miami/JFK Medical Center Palm Beach Regional GME Consortium, Atlantis, Florida, USA
2Department of Internal Medicine, Monmouth Medical Center, Long Branch, New Jersey, USA
*Corresponding author: Agrawal A, Chief Resident, Department of Medicine, Monmouth Medical Center, Long Branch, NJ, USA, Tel:

7328612184; E-mail:
Rec date: Dec 21, 2015; Acc date: Dec 30, 2015; Pub date: Jan 6, 2016
Copyright: © 2016 Shah V, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

propafenone can be used in patients with obstructive lung
disease who do not have bronchospasm.
COPD is one of the leading causes of Mortality & Keywords: Chronic obstructive pulmonary disease;
Morbidity in the US and is associated with a wide variety Atrial fibrillation
of cardiovascular diseases especially arrhythmias, angina,
myocardial infarction and congestive heart failure and is
directly associated with the severity of COPD described in Introduction
the GOLD initiative. COPD is an independent risk factor for
AF/AFL. Smoking, hypoxia and inflammation all contribute Chronic obstructive pulmonary disease (COPD) is a major
to AF in COPD patients mainly via atrial remodeling while global public health problem. COPD is a common preventable
hypercapnia contributes to it via increasing refractoriness and treatable disease, which is characterized by persistent
of the atrial musculature and a delay in the return of the airflow limitation that is usually progressive and associated
refractoriness to normal after resolution of the with an enhanced chronic inflammatory response in the
hypercapnia. The most common EKG abnormality found in airways and the lung to noxious particles or gases. In 2020,
patients with COPD is P pulmonale and the PQ interval is COPD is projected to rank fifth worldwide in terms of burden
the strongest predictor of developing AF. The P wave of disease and third in terms of mortality [1] though presently
Dispersion (PwD) was also an independent risk factor for it is the 4th leading cause of Mortality and the 2nd leading
the development of AF and was found to be more in the cause of Morbidity in the United States (US) [2].
acute phase than in the stable phase.
Extra-pulmonary manifestations of COPD include
The BODE index, an important prognostic score among cardiovascular disease, skeletal muscle dysfunction,
patients hospitalized with a COPD exacerbation has a osteoporosis, metabolic syndrome depression and lung cancer
direct co relation with the prevalence of AF/AFL while the [1]. COPD is associated with specific electrocardiographic (EKG)
DECAF score, which was found to be superior to the CURB abnormalities while an increased incidence of cardiac
65 score as a mortality predictor for hospitalized patients, arrhythmias has been reported which includes atrial fibrillation
includes AF as one of the criteria. Chronic hypoxemia is (AF), atrial flutter (AFL), multifocal atrial tachycardia (MAT) and
one of the main reasons for altered pulmonary vein non-sustained ventricular tachycardia (NSVT) [3]. It is
anatomy and hence the presence of COPD was identified estimated that there were approximately 33.5 million people
as an independent risk factor for the recurrence of atrial with AF in 2010 worldwide (20.9 million men [95% uncertainty
tachyarrhythmias after catheter ablation in patients with interval (UI), 19.5-22.2 million] and 12.6 million women [95%
COPD and the absence of COPD was also found to be an UI, 12.0-13.7 million]) [4] and it was also estimated that the
independent predictor for a successful electro- burden of AF in the United States alone would increase to at-
cardioversion. These patients were also found to have an least 5.6 million by 2050 [5].
increased incidence of non-PV foci for the arrhythmias.
Oral glucocorticoids were associated with an increased
risk of developing AF especially high dose steroids. It is COPD and Cardiovascular Disease
recommended to correct the underlying respiratory
decompensation while treating patients with AF as they Patients with diagnosed and/or undergoing treatment for
render the treatment of AF ineffective. Non- COPD are at a substantially increased risk of hospitalizations
dihydropyridine calcium channel blockers should be used and mortality due to heart diseases. In one retrospective
as first line rate control agents for AF in patients with cohort study, the prevalence of cardiovascular diseases (CVD)
concomitant COPD while the β-blockers, sotalol, was higher in the COPD group than the control group. After all
the cardiovascular risk factors were adjusted for odds ratios of

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coronary artery disease.1 No.25 mV in the inferior leads) is There seem to be a wide variety of reasons for arrhythmias usually omnipresent on EKG’s of patients with chronic lung to occur in COPD beginning from risk factors. moderate. gender. The Forced Vital Capacity (FVC).89).61 (CI: 1.47-1.8-times higher for FEV1 between 60-80% of expiration from a position of full inspiration.7 [1]. The Copenhagen City Expiratory Volume in one second (FEV1). Expressed in liters and the Forced relationship between FEV1.0001 infections of the upper respiratory tract and infections of the and p<0. endothelium of the atrial arteries in the AF group as compared 11. causes an 2 (OR 2.1:2 prevalence were: arrhythmia 1. p<0.0. and a 60-70% 1.0001. attempted to postulate the reasoning for the development in patients with P pulmonale [20]. 0. p<0. tracheobronchial tree [1]. angina 1. hypoxia. chronic kidney disease. very predictor of AF [17]. potentially causes atrial remodeling.9% vs.0% vs. VEGF and MMP-9 within the associated with an increased likelihood of AF/AFL (23. its effect in diseases. the model. diabetes and body mass Global Initiative for Chronic Obstructive Lung Diseases (GOLD) index. An association was also pathophysiology of COPD and now postulations have also been established between the severity of airflow obstruction based made of its impact in atrial remodeling and thus causing and on the GOLD criteria and the prevalence of CVD which showed potentially worsening existing AF [12]. blood pressure. airway inflammation. anemia. upregulation of Vascular Endothelial Growth Factor (VEGF) 95% CI 2. commonly seen in patients with COPD.0001). FEV1 ≥80% predicted. 5.9 ms vs. conduction time however. P=0. It was shown via smoking and blood pressure [9]. They also showed that the risk of AF hospitalization was classifies the severity of airflow limitation as determined by 1.6%.0 to 4.4 ± 17. gender. expressed in liters predicted compared with a FEV1 of ≥80% after adjustment for are the major determinants of the severity of COPD [1. to patients without AF [13]. Hayashi et al. significantly longer in the AF group than in the non-AF group pulmonary hypertension.0001) and that it of the disease and common causes for this are usually viral remained a significant predictor of AF/AFL and NSVT (p<0. mild.4 ms. FEV1 ≥50% but <80% predicted. which is the difference in the maximum and They concluded that the pro fibrotic response of nicotine in minimum duration of the P wave. respectively. 107. showed that tobacco use. 1.56-4. p<0. FEV1 <30% predicted) using the fixed ratio.14). Chronic Obstructive Pulmonary Diseases 2016 Vol.0001). respectively) after adjusting for age.7]. that prevalence of CVD was higher among subjects with GOLD Hypoxia. 153. of AF/AFL after cardioversion in women while an increased risk of mortality and not arrhythmia was found in men [11]. hypercapnia and high values heart failure.9%. GOLD 2.0 ± 17. 1.2 ± 25. acute myocardial decrease in the levels of miRNAs miR-133 and miR-590 was infarction 1. and GOLD 4.81). was also found to be an upregulation of expression of Transforming Growth Factor Beta independent risk factor associated in the development of AF 2 This article is available from:http://chronic-obstructive-pulmonary-disease. smoking.2 ms vs.3 ± contribute to ultimately causing or worsening AF [11-15]. age. They concluded that the PQ interval is the strongest stratifier for AF Shan et al. there was a delay in only the conduction time to return to normal after the COPD and Atrial Fibrillation: Potential resolution of hypercapnia prompting the theory that this differential recovery time may be the reason for an increased Causes of Arrhythmia and EKG incidence of AF observed in the phase of eucapnia [19].0%.43-1. obesity. Matrix metalloproteinase 9 (MMP9) established an inverse co-relation between the FEV1 and rate expression is increased in the atrium in a patient with AF and of incident AF which was independent of age. Stevenson et al. of pulmonary artery systolic pressure are independent and rate/rhythm control medications [10]. 95% CI 2. Immunofluorescence that there was excess production and co- A recent retrospective study showed that of COPD were localization of HIF-1α. In their experimental sheep a succinct overview of the association of COPD with AF. NSVT (13. GOLD 3. P=0.9. compared with normal subjects [8]. 23. and inflammation are two of the major factors in the bronchodilator FEV1/FVC <0. .76). The secondary to an increase in Hypoxia-induced transcription Atherosclerosis Risk in Communities (ARIC) cohort study factor-1α (HIF-1α). proving that reduced lung function as an independent severe.84 (CI: critical in atrial remodeling in the canine atrium [16]. Terzano et al. cancer. The P wave increased incidence of AF in smokers using a canine model. and sustained ventricular tachycardia Patients with COPD are prone to have acute exacerbations (SVT. FVC with AF. BMI. congestive heart failure 3.5).2 ms.4 to 3.76 (confidence interval [CI]: 1(TGF-β1) and TGF-βRII at the protein level. β-adrenergic agonist and steroids all (115. hypertension.8 times with a FEV1 of ≤60% compared with a FEV1 of ≥80%. defined as the maximal volume of air exhaled with maximally forced effort from a It has been shown consistently that there exists an inverse maximal inspiration. Smoking 3. dispersion (PwD). Smoking. showed the hypercapnia caused an arrythmogenic mechanisms and potential treatment increase in the atrial musculature refractoriness and the strategies.imedpub. respectively.3 times more with a FEV1 between 60-80% of predicted and spirometry into 4 grades (GOLD 1.6) and GOLD 3 or 4 COPD (OR 3.0001. This article provides predictors of incident AF [18]. diabetes. It is well documented that oxidative stress severe.3% vs. There was also an increased risk of hospitalization was found to be an independent risk factor in the recurrence secondary to cardiovascular causes in the COPD group [6]. defined as the Heart Study demonstrated that the Risk of new AF at re- maximal volume of air exhaled in the first second of a forced examination was 1. Changes P pulmonale (P wave ≥0. FEV1 ≥30% but <50% predicted.64-1.0003 and 166. hypercapnia.61 (CI: 1. in a digital analysis of EKG’s in a 25 year altering cardiopulmonary physiology to the treatment of period showed P-wave duration and PQ interval were COPD. respectively). The sex. suboptimal pulmonary function. intriguingly. respectively.

an anticholinergic or a combination The BODE index is a multidimensional 10-point scale which of the two. control in these patients while Amiodarone and Digoxin can also be used. consolidation. Left atrial enlargement. degree of airflow obstruction and trials of β-2-agonist treatment in patients with obstructive dyspnea and exercise capacity measured in 6-min walk test airway disease performed concluded that the initiation of and the score is directly proportional with mortality. Chronic Obstructive Pulmonary Diseases 2016 Vol. ablations for AF. HATCH score was an abbreviation for heart failure.557) were the independent contraindicated in patients with bronchospasm however the β predictors for higher atrial tachyarrhythmia recurrence [28].11-4. MRC Dyspnea Score. In hemodynamically unstable patients. They also showed guidelines. case control study current glucocorticoid use was associated with an increased risk of AF or AFL compared with never use (adjusted OR. 95% confidence COPD and its Effect on Ablation interval [CI]. sotalol. This causes an steroids were associated with an increased risk of arrhythmias increased level of inflammatory markers that promotes fibrosis especially AF [32]. an increased incidence of AF as compared to [25].129-2.e.62 (95% CI.765) as well as the presence of COPD (P=0. eosinopenia. 1. increased risk of AF or arrhythmias while theophylline and oral increased pulmonary vascular resistance. mechanisms along with β-1 adrenergic stimulation [14]. Consolidation. The Dyspnea. 95% CI: should be avoided in patients with AF. COPD Treatment Strategies and hypertension. likely through these and SVT [23]. blockers. In their study. Huerta et al. not uncommon in the treatment of COPD.013. A meta-analysis of randomized placebo-controlled integrates body mass index. its progression and mortality.767. therapy with a β-2 agonist.951. etc. Per the AHA/ACC/HRS (American Heart Association/ showed that significant alteration of pulmonary vein (PV) American College of Cardiology/ Heart Rhythm Society) anatomy was related to arrhythmogenicity. Non β-1 selective 1. In another case control study by van der Hooft et al.025) and all the non-PV foci were located in the right antiarrhythmic drugs or cardioversion are likely to be atrium [27]. In CURB65 [24].029. In a Meta-Analysis from 2013 on and thus causes structural remodeling of pulmonary vessels Roflumilast. 3.06) while among new glucocorticoid users. found to be independent predictors of AF progression [26]. Roh et al.79-2. a population based.1 No.22) (15). The excluded patients with major cardiovascular events [33]. propafenone and adenosine are OR=1. They also recommend a non-dihydropyridine the absence of COPD was also an independent predictor of calcium channel blocker as the first line therapy for rate sinus rhythm at a 1 yr follows up [29]. blockers. prevention and therapy of acute mainstay treatment for COPD patients.0%. the latter in patients with preserved left ventricular ejection fraction. AF. findings strongly COPD has a significant effect on cardiopulmonary physiology showed that patients receiving high-dose corticosteroid but also has an impact in altering the anatomy of the same therapy. COPD is showed that inhaled steroids were not associated with an associated with hypoxemia and acidosis. Eosinopenia. It was treatment increases heart rate and reduces potassium shown that patient’s with higher BODE index scores had a concentrations compared to placebo and it causes adverse significantly greater prevalence of arrythmias including AF/AFL cardiovascular events like CHF.070-3. acidemia. The DECAF score includes in patients receiving tiotropium vs placebo [30]. At the Acidemia and atrial Fibrillation (DECAF) score was introduced same time the side effect profile of tiotropium was studied in by Steer et al. and atrial fibrillation and Diabetes Mellitus. gave rise to the HATCH score while likely due to chance as most of the studies in the analysis had studying AF progression from paroxysmal to persistent. Long term the 5 strongest predictors of mortality i. 1.92. glucocorticoid use is well known to cause hypertension. HF and ischemic was found to be a stronger than the other predictors like the heart disease all of which can directly or indirectly cause AF. sotalol and propafenone can be considered in Absence of COPD was found to be an independent predictor patients with obstructive lung disease who do not have for a successful electro-cardioversion in patients with AF while bronchospasm. previous episode of transient ischemic attack or stroke. optimizing therapy for the underlying lung disease that non-PV foci were more common in the chronic lung with correction of the hypoxia and acidosis in patients with disease group (26. age. It includes beginning exacerbation of COPD [22].7%) than in the control group (5. The impact of COPD on outcomes of catheter ineffective until the respiratory decompensation has been ablation in patients with AF in terms of recurrence was corrected. OR=1. as a predictor of mortality in hospitalized the UPLIFT trial and found no difference in the incidence of AF patients with COPD exacerbations. which leads to. which were all. which showed agonists have the propensity to precipitate AF and hence that non-paroxysmal AF (P=0. Bronchodilator agents like Theophylline and β evaluated in a prospective study by Gu et al. 95% CI: 1. A subgroup analysis of the European Heart Survey (EHS) placebo was seen however the writers pointed out that this is on AF by de Vos et al.1:2 [21] and the PwD was found to be increased more in the acute phase than in stable phase and is greater in patients with more COPD Treatment Causing AF frequent exacerbations suggesting that the PwD could be a Inhaled bronchodilator medications continue to remain the target for prediction. direct cardioversion is recommended while AV nodal ablation or ventricular pacing may be needed to control the © Copyright iMedPub 3 . COPD developing AF is the cornerstone for management as the P=0. strategies of AF the adjusted OR was 3. are at system because of which it affects outcomes of catheter increased risk of developing atrial fibrillation [31].

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