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prevalence were: arrhythmia 1.76 (confidence interval [CI]: 1(TGF-1) and TGF-RII at the protein level, and a 60-70%
1.64-1.89), angina 1.61 (CI: 1.47-1.76), acute myocardial decrease in the levels of miRNAs miR-133 and miR-590 was
infarction 1.61 (CI: 1.43-1.81), congestive heart failure 3.84 (CI: critical in atrial remodeling in the canine atrium [16]. Smoking
3.56-4.14). 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]. of AF/AFL after cardioversion in women while an increased risk
of mortality and not arrhythmia was found in men [11].
The Forced Vital Capacity (FVC), 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, Expressed in liters and the Forced relationship between FEV1, FVC with AF. The Copenhagen City
Expiratory Volume in one second (FEV1), 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 1.8-times higher for FEV1 between 60-80% of
expiration from a position of full inspiration, expressed in liters predicted compared with a FEV1 of 80% after adjustment for
are the major determinants of the severity of COPD [1,7]. The sex, age, smoking, blood pressure, diabetes and body mass
Global Initiative for Chronic Obstructive Lung Diseases (GOLD) index. They also showed that the risk of AF hospitalization was
classifies the severity of airflow limitation as determined by 1.3 times more with a FEV1 between 60-80% of predicted and
spirometry into 4 grades (GOLD 1, mild, FEV1 80% predicted; 1.8 times with a FEV1 of 60% compared with a FEV1 of 80%,
GOLD 2, moderate, FEV1 50% but <80% predicted; GOLD 3, proving that reduced lung function as an independent
severe, FEV1 30% but <50% predicted; and GOLD 4, very predictor of AF [17]. It is well documented that oxidative stress
severe, FEV1 <30% predicted) using the fixed ratio, post- and inflammation are two of the major factors in the
bronchodilator FEV1/FVC <0.7 [1]. 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].
that prevalence of CVD was higher among subjects with GOLD
Hypoxia, commonly seen in patients with COPD, causes an
2 (OR 2.9, 95% CI 2.4 to 3.6) and GOLD 3 or 4 COPD (OR 3.0,
upregulation of Vascular Endothelial Growth Factor (VEGF)
95% CI 2.0 to 4.5), compared with normal subjects [8]. The
secondary to an increase in Hypoxia-induced transcription
Atherosclerosis Risk in Communities (ARIC) cohort study
factor-1 (HIF-1). 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, gender, BMI,
potentially causes atrial remodeling. It was shown via
smoking and blood pressure [9].
Immunofluorescence that there was excess production and co-
A recent retrospective study showed that of COPD were localization of HIF-1, VEGF and MMP-9 within the
associated with an increased likelihood of AF/AFL (23.3% vs. endothelium of the atrial arteries in the AF group as compared
11.0%, respectively, p<0.0001), NSVT (13.0% vs. 5.9%, to patients without AF [13].
respectively, p<0.0001), and sustained ventricular tachycardia
Patients with COPD are prone to have acute exacerbations
(SVT; 0.9% vs. 1.6%, respectively, p<0.0001) and that it
of the disease and common causes for this are usually viral
remained a significant predictor of AF/AFL and NSVT (p<0.0001
infections of the upper respiratory tract and infections of the
and p<0.0001, respectively) after adjusting for age, gender,
tracheobronchial tree [1]. Terzano et al. showed that
tobacco use, obesity, hypertension, coronary artery disease,
suboptimal pulmonary function, hypercapnia and high values
heart failure, diabetes, anemia, cancer, chronic kidney disease,
of pulmonary artery systolic pressure are independent
and rate/rhythm control medications [10]. This article provides
predictors of incident AF [18]. In their experimental sheep
a succinct overview of the association of COPD with AF, the
model, Stevenson et al. showed the hypercapnia caused an
arrythmogenic mechanisms and potential treatment
increase in the atrial musculature refractoriness and the
strategies.
conduction time however, intriguingly, 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].
Changes P pulmonale (P wave 0.25 mV in the inferior leads) is
There seem to be a wide variety of reasons for arrhythmias usually omnipresent on EKGs of patients with chronic lung
to occur in COPD beginning from risk factors, its effect in diseases. Hayashi et al, in a digital analysis of EKGs in a 25 year
altering cardiopulmonary physiology to the treatment of period showed P-wave duration and PQ interval were
COPD. Smoking, airway inflammation, hypoxia, hypercapnia, significantly longer in the AF group than in the non-AF group
pulmonary hypertension, -adrenergic agonist and steroids all (115.4 17.2 ms vs. 107.0 17.2 ms, P=0.0003 and 166.3
contribute to ultimately causing or worsening AF [11-15]. 23.9 ms vs. 153.2 25.4 ms, P=0.0001, respectively). They
concluded that the PQ interval is the strongest stratifier for AF
Shan et al. attempted to postulate the reasoning for the development in patients with P pulmonale [20]. The P wave
increased incidence of AF in smokers using a canine model. dispersion (PwD), which is the difference in the maximum and
They concluded that the pro fibrotic response of nicotine in minimum duration of the P wave, was also found to be an
upregulation of expression of Transforming Growth Factor Beta independent risk factor associated in the development of AF
[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, prevention and therapy of acute mainstay treatment for COPD patients. It includes beginning
exacerbation of COPD [22]. therapy with a -2 agonist, an anticholinergic or a combination
The BODE index is a multidimensional 10-point scale which of the two. A meta-analysis of randomized placebo-controlled
integrates body mass index, degree of airflow obstruction and trials of -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. It was treatment increases heart rate and reduces potassium
shown that patients 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, AF, etc. likely through these
and SVT [23]. The Dyspnea, Eosinopenia, Consolidation, mechanisms along with -1 adrenergic stimulation [14]. 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, as a predictor of mortality in hospitalized the UPLIFT trial and found no difference in the incidence of AF
patients with COPD exacerbations. The DECAF score includes in patients receiving tiotropium vs placebo [30]. Long term
the 5 strongest predictors of mortality i.e. MRC Dyspnea Score, glucocorticoid use is well known to cause hypertension,
eosinopenia, consolidation, acidemia, and atrial fibrillation and Diabetes Mellitus, Left atrial enlargement, 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. In
CURB65 [24]. a population based, case control study current glucocorticoid
use was associated with an increased risk of AF or AFL
compared with never use (adjusted OR, 1.92; 95% confidence
COPD and its Effect on Ablation interval [CI], 1.79-2.06) while among new glucocorticoid users;
strategies of AF the adjusted OR was 3.62 (95% CI, 3.11-4.22) (15). In another
case control study by van der Hooft et al, 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, not uncommon in the treatment of COPD, are at
system because of which it affects outcomes of catheter increased risk of developing atrial fibrillation [31]. Huerta et al.
ablations for AF, its progression and mortality. COPD is showed that inhaled steroids were not associated with an
associated with hypoxemia and acidosis, which leads to, increased risk of AF or arrhythmias while theophylline and oral
increased pulmonary vascular resistance. This causes an steroids were associated with an increased risk of arrhythmias
increased level of inflammatory markers that promotes fibrosis especially AF [32]. In a Meta-Analysis from 2013 on
and thus causes structural remodeling of pulmonary vessels Roflumilast, an increased incidence of AF as compared to
[25]. 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, 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. The excluded patients with major cardiovascular events [33].
HATCH score was an abbreviation for heart failure, age,
previous episode of transient ischemic attack or stroke, COPD Treatment Strategies
and hypertension, which were all, found to be independent
predictors of AF progression [26]. In their study, Roh et al. 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. They also showed guidelines, 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 (26.7%) than in the control group (5.0%; COPD developing AF is the cornerstone for management as the
P=0.025) and all the non-PV foci were located in the right antiarrhythmic drugs or cardioversion are likely to be
atrium [27]. 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. Bronchodilator agents like Theophylline and
evaluated in a prospective study by Gu et al, which showed agonists have the propensity to precipitate AF and hence
that non-paroxysmal AF (P=0.013, OR=1.767, 95% CI: should be avoided in patients with AF. Non -1 selective
1.129-2.765) as well as the presence of COPD (P=0.029, blockers, sotalol, propafenone and adenosine are
OR=1.951, 95% CI: 1.070-3.557) were the independent contraindicated in patients with bronchospasm however the
predictors for higher atrial tachyarrhythmia recurrence [28]. blockers, 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. 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]. control in these patients while Amiodarone and Digoxin can
also be used, the latter in patients with preserved left
ventricular ejection fraction. In hemodynamically unstable
patients, direct cardioversion is recommended while AV nodal
ablation or ventricular pacing may be needed to control the
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Chronic Obstructive Pulmonary Diseases 2016
Vol.1 No.1:2
ventricular rate with the cardioversion posing challenges of its 6. Curkendall SM, Lanes S, de Luise C, Stang MR, Jones JK, et al.
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were significant improvements in quality of life scores in cardiovascular outcomes. European journal of epidemiology; 21:
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cardiology;115:135-143.
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remodeling of fibrillated atria the consequence of tissue
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