Prevalence of Cardiac Arrhythmias among Chronic Obstructive Pulmonary Disease Patients Admitted to Jimma University Medical Center
Abstract
Background: Cardiac arrhythmias are common in COPD patients and are a major cause of morbidity and mortality.
Aim and Objective: The present study aimed to determine the prevalence of cardiac arrhythmias among patients with COPD
Materials and Methods: The study was conducted on COPD
patients visiting chest clinic of Jimma University Medical Center (JUMC)
located at Jimma town, South west Ethiopia; from May 18 to August 18,
2017 G.C. A hospital based cross-sectional study was conducted among 80
sampled COPD patients; and an investigation for 12 Lead resting supine
ECG was performed. The results of ECG patterns and other variables were
entered into EPI data (3.1) and exported to SPSS (20) for further
analysis.
Results: The prevalence of arrhythmia accounted for 50% and
the magnitude of its types were classified as Sinus origin arrhythmia
(30%) specifically [Sinus bradycardia (16.3%), Sinus tachycardia (8.8%)
and Sinus arrhythmia (5.0%)], Ectopic arrhythmia (20%) specifically
[Premature ventricular Contraction (7.5%), Atrial fibrillation (6.3%),
Premature atrial contraction (3.8%), Atrial flutter (1.3%) and Multi
focal atrial tachycardia (1.3%)] Conduction block arrhythmia (23.8%)
specifically[Bundle branch block (17.5) for instance: Complete right
bundle branch block (3.8%), Complete left bundle branch block (5%),
Incomplete right bundle branch block (7.5%), Incomplete left bundle
branch block (1.3%), Hemi fasicular block (5%)] and Atrioventricular
block (1.3%)], and Other arrhythmia (11.4%) like Prolonged QTc interval
(8.8%) and Preexcitation syndrome or Wolf Parkinson white syndrome
(2.5%) as a single COPD patient presented with more than arrhythmias.
Conclusion: Routine ECG investigation should be performed at
the setup to screen and initiate early management of Cardio vascular
diseases including cardiac arrhythmias for better prognosis COPD
patients which was inevitable and very common.
Abbreviations: COPD: Chronic Obstructive
Pulmonary Disease; COLD: Chronic Obstructive Lung Disease; CVDs:
Cardiovascular Disorders; AF: Atrial Fibrillation; FVC: Forced Vital
Capacity
Abbreviations: PL: Poloxamer; PEO: Poly
Ethylene Oxide; PPO: Poly Propylene Oxide; BUD: Budesonide; SAXS: Small
Angle X-ray Scattering; UC: Ulcerative Colitis; CD: Cyclodextrins
Introduction
Chronic Obstructive Pulmonary Disease (COPD) is a chronic preventable
and treatable multi-system disease where pulmonary component is
characterized by significant none fully reversible progressive airflow
limitation, often associated with an abnormal inflammatory response of
the lung to noxious particles or gases. The best known and widely
accepted definition is promulgated by global initiative for chronic
obstructive lung disease (COLD), with a post bronchodilator cut-off
point of FEV1/FVC ratio <70 [1]. COPD is a leading cause of mortality
and morbidity, as WHO estimating it is expected to be third leading
cause of death and disability by the year 2020 which has been sixth and
fourth in 1990 and 2000 respectively [2]. The prevalence in Africa,
though low due to problems of screening like scarce of spirometry, it is
expected to rise as a result of an increasingly ageing population and
increasing prevalence of the habit of cigarette smoking and exposure to
biomass fuel [3].
Heart is the most targetable organ for COPD as systemic complication
and develops much pathology of cardiovascular disorders (CVDs) or
cardiovascular complications, among which cardiac arrhythmia is the
commonest but also other CVDs (angina, hypertension, coronary artery
disease and congestive health failure) by sharing different risk factors
(advanced age, smoking, environmental pollutants, gender, and
socioeconomic status) [49]. COPD increases the risk of cardiac
arrhythmias and they tend to occur with increasing frequency especially
in situations of acute exacerbation, respiratory failure and increasing
comorbidities and also vice versa where COPD is highly prevalent among
CVDs (about 22.6%) and in cardiac arrhythmia patients especially in
Atrial fibrillation (AF) patients (the prevalence of COPD was from
11%-18.6%), and is associated with higher rates of cardiovascular death,
all-cause death, and aggravates outcome of any death [10-
12].Arrhythmias have been associated with increased hospital admission,
confers a poor prognosis, morbidity and mortality in COPD
patients[4,13-15].
Large studies have shown that cardiovascular events are a leading
cause of COPD-related mortality, and there is limited evidence
suggesting that some of these events may be partly caused by arrhythmias
[16-19]. A number literature explains the mechanism/ factors for
development of arrhythmias in COPD patients secondary to adverse effects
of medications like theophylline [20,21], B-agonists like salbutamol
[22,23], steroids [23], anticholinergics [24], due to Cardiac autonomic
dysfunction [25-28] or from ventricular failure [29]. In a health care
system especially in our setting grappling with competing priorities,
the importance of preemptive and early identifications of amenable
conditions cannot be overemphasized which was ideally enable appropriate
and cost-effective allocation of resources from complication of the
disease by early screening and initiate timely management of systemic
complication. One of the screenings is using simple tool like ECG to
detect cardiovascular complication including arrhythmia among COPD
patients. There is so far no study in our setup on the prevalence or the
burden of cardiac arrhythmias among COPD patients as even ECG, simple
tool is not routinely practiced. Thus, the present study, will help in
establishing the burden of the problem, form a basis for further
research and possibly generate recommendations on how this problem
should be approached.
Subjects and Methods
Study Design and Setting
The study was conducted at JUMC, Jimma, one of the towns in Oromia
regional state, located at South West Ethiopia, with distance of 357 Km,
away from the capital city, Addis Ababa. JUMC is one of the largest
teaching referral hospitals in the country, providing the health service
at inpatient and outpatient level for the catchment area (more than 15
million populations) indwelling in the South West of the country. The
health service is delivered by specialists, medical residents, medical
interns and other health professionals. The study was conducted from May
18 to August 18, 2017 G.C among a sampled 80COPD patients attending
chest clinic of JUMC by employing a hospital based cross-sectional study
design. The study populations were all COPD patients attending chest
clinic of JUMC who were available during data collection period.
Data Collection (Instrument, Technique)
Dynamic pulmonary function test was carried out to diagnose and grade
severity of COPD based on post bronchodilator result of forced
expiratory volume in one second (FEV1) % predicted, forced vital
capacity (FVC) and (FEV1/FVC) ratio as per the guideline of COLD (1) by
using dry digital spirometry (carefusion, Germany). Standard 12-lead
supine resting ECG (NIHON KOHDEN Cardiofax S) was used with machine
calibrated on 1 mV for a 10 mm (0.1 mV/mm) at speed of 25 mm/s, where
each small box and large box represents 0.04 sec and 0.2 sec
respectively. 10 electrodes (4 limb electrodes at right and left arms
and legs + 6 chest electrodes (V1- V6)) were placed on client's arms,
legs and chest after orientation and gel applied, yielding a total of 12
leads that measures the potential difference of movement of electrical
activity of the heart.
Each ECG paper was visually analysed for recording errors, manually
interpreted by investigator in liaison with the cardiologist and
classified according to the Minnesota coding criteria [30], merged and
thematised to different main and sub-categories for simplicity.
Data Processing and Analysis
Data was checked, categorized, coded & entered into EpiData
version 3.1 after template formed and finally exported to SPSS version
20 for further analysis. Descriptive statistics like frequencies and
percentages were used to describe the findings.
Ethical Clearance
Implementation of the proposal was carried out after getting approval
letter from the ethical clearance committee/ethical review board of
Jimma University (IRB/699/2017). An official letter of collaboration and
permission request to chest and cardiac clinic of JUMC (for permission
of instruments, ECG and spirometry) was obtained from Department of
Physiology and Internal medicine prior to study conduction. Informed
verbal and written consent were taken from the respondents/clients after
explaining the objectives and purpose of the study. The participants
were assured that they have full right to participate or withdraw from
the study and the collected data/ information were kept confidentially.
Any abnormal finding of ECG pattern (arrhythmia) observed was required
consultation of physicians of chest and cardiac clinic for further
interventions.
Results
Baseline Characteristics of COPD Patients
From the total sampled 80 COPD patients attending chest clinic of
JUMC from May 18 to August 18, 2017 G.C, the mean age was 55.1±13.66
that ranges from 26-90 years by which majority of them (32.5%) belongs
to interval of 51-60 years with the ratio of males to females of 43/37
(1.16:1). Majority of COPD patients (63.75%) were experienced smoking
while 60% of them especially females but also males indwelling the rural
area were exposed to dusts and biomass full. The mean of
post-bronchodilator FEV1% predicted was (42.5±15.6) as shown in detailed
in Table 1.
Prevalence of Arrhythmia among COPD Patients
Out of the total analysed, interpreted and categorized ECG papers
based on the Minnesota coding criteria from the sampled 80 COPD patients
by investigator in liaison with the cardiologist, the prevalence of
arrhythmia accounted about 50% or diagnosis of 40 ECG papers out of
total analysed 80 ECG papers with cardiac arrhythmia. This magnitude is
expected higher if detected by Holte ECG that applied for 24 hours, but
it is not available in the setup. Thus, a simple ECG that detects
patients' cardiac status in a specific time was used instead with its
possibility of missed diagnosis of some types of arrhythmias especially
ventricular origins. The types of arrhythmia and their specific
magnitude or frequency among COPD patients were analysed as follows with
emphasis of possibility of presence of more than one type of arrhythmia
within a single patient as detailed in Table 2.
Table 1: Magnitude of different types of arrhythmias among
COPD patients attending chest clinic of JUMC from May 18 to August 18,
2017 G.C, n=80.
What have to be emphasized is, either the outcome variable (status of
patients ECG paper) was sinus normal rhythm or arrhythmic, or finally
the frequency was computed and yields 50% of diagnosed cardiac
arrhythmia, while left proportion might be normal sinus rhythm or can be
other abnormal ECG than arrhythmia. So, the frequency was not summated
with different arrhythmias, but simply the proportion of specific
arrhythmia per to total analysed ECG paper.
Sinus Origin Arrhythmias (SOA)
The sinus origin arrhythmia is the most common types of arrhythmia
(30%) that detected among COPD patients. This can also be further
classified to subgroups with their specific magnitude per to total
analysed ECG papers, not per to occurred arrhythmias. For instance,
Sinus bradycardia accounted for 16.3%, Sinus tachycardia (8.8%) and
Sinus arrhythmia (5.0%).
Ectopic Arrhythmias (EA)
Ectopic arrhythmia or non-sinus origin arrhythmia accounts 20%,
specifically from its subgroups the occurrence of premature ventricular
Contraction was relatively highest (7.5%), Atrial fibrillation (6.3%),
Premature atrial contraction (3.8%), Atrial flutter (1.3%) and Multi
focal atrial tachycardia (1.3%) among sampled COPD patients.
Conduction Block Arrhythmias (CBA)
Conduction block arrhythmia is also the second most prevalent (23.8%)
types of arrhythmia diagnosed among COPD patients, classified as Bundle
branch block (17.5%) with further division of complete bundle branch
block; right (3.8%) and left (5%), incomplete bundle branch block; right
(7.5%) and left (1.3%), Hemi fasicular block (5%) and Atrioventricular
block also known as heart block (1.3%).
Other Arrhythmias (PES or WPWS)
Other arrhythmia accounts about 11.4% of arrhythmia observed among
COPD patients. For instance, Preexcitation syndrome or Wolf Parkinson
white syndrome and Prolonged QTc interval were discriminated by the
magnitude of 2.5% and 8.8% respectively.
Discussion
The mean age of the subjects in the present study was (55.1±13.66)
years, while majority of the patients (32.5%) classified at interval of
51-60 years indicates also in our setup, COPD still remains a disease of
the elderly. Though, COPD was a predominantly male disease, the present
study finding indicates nearly similar a male to female ratio (1.16:1).
This may be not due to the low prevalence of cigarette smoking among
our female population but additional burden of females' exposure to
biomass fuel. The prevalence of cardiac arrhythmia in the present study
was 50% which was highest and in line with studies of Hudson et al. [15]
who reported the prevalence of cardiac arrhythmia 47%. The finding of
Warnier et al. [31] shows nearly similar magnitude of different types of
arrhythmia with the present finding. Because both study used the same
tool (Minnesota coding criteria) for classification of arrhythmia. But
the magnitude of cardiac arrhythmia reported by the study of Kleiger et
al. [14] and Shih et al. [32], H Zaghla et al. [33] was higher than the
present finding.
This difference might be because they involved only patients with
severe stage of COPD, but the present study involved COPD patients from
all stages. The 50% prevalence of cardiac arrhythmia diagnosed in the
present study was also against the finding of Curkendall et al. [4] with
lowest prevalence of 21.1%, Cazzola et al.[34] with prevalence of 15.9%
due to possible sample size difference, difference in severity of the
disease, difference in design method, they exclude also sinus origin
arrhythmias like sinus tachycardia and bradycardia which is actually
diagnosed in the present study as sinus origin arrhythmia. Though, the
arrhythmogenic mechanisms involved in COPD are complex and seem to have
diversity across the different types of arrhythmias, the common causes
for the occurrence of arrhythmias in COPD are P-wave duration and PQ
interval, oxidative stress, inflammation, hypoxia, hypercapnia,
pulmonary hypertension, p-adrenergic effects of bronchodilators,
diastolic dysfunction, changes in atrial size by altered respiratory
physiology, increased arrhythmogenicity from no pulmonary vein foci of
right atrium, autonomic dysfunction, QTc dispersion, concomitant CAD and
HF [24,35,36].
The specific cardiac arrhythmias are discussed for their
arrhythmogenic mechanisms as follows: MAT exclusively associated with
COPD, developed due to increased intracellular calcium stores that
induced by hypokalemia, hypoxia, acidemia, and increased catecholamines
as the principal underlying mechanism [37,38]. AF is also the most
prevalent (6.3%) in the present study among COPD patients due to
prolonged and inhomogeneous propagation of depolarization of atria where
the right atrial electromechanical delay is significantly prolonged and
negatively correlated with FEV1 that resulted in P-pulmonale, prolonged
P-wave duration and PQ interval as a feature of AF [39]. Oxidative
stress and inflammation represent major pathogenic mechanisms in AF
development and perpetuation in COPD patients and facilitate atrial
remodeling [4043] Decreased oxygenation, a feature of COPD, serve also
as an initiating and perpetuating factor in AF through cascade of
hypoxia- induced vascular endothelial growth factor (VEGF) expression
which contribute to atrial structural remodeling of AF and hypoxia
related indirect effect of hypercapnia for a marked and uniform increase
in atrial refractoriness and a significant slowing in atrial conduction
[44,45].
Other mechanisms are also involved for potentially linking COPD with
AF (pulmonary hypertension [46,47], p-adrenergic effects of
bronchodilators [23], diastolic dysfunction [48], changes in atrial size
by altered respiratory physiology [49] and increased arrhythmogenicity
from nonpulmonary vein foci in the right atrium [50]. Multiple potential
mechanisms for ventricular arrhythmogenesis in COPD patients are
Inhaled p-adrenergic agonists decreasing ventricular refractoriness
[51], Autonomic neuropathy [27,52] as indexes of cardiac autonomic
dysfunction (heart rate variability and heart rate turbulence) [53].The
other arrhythmogenesis mechanism of most occurred types of cardiac
arrhythmia (ST (8.8%), PVC (7.5%) and PAC (3.8%)) among the COPD
patients due to adverse effects methylxanthine agents such as
theophylline and aminophylline in short and long use which are
well-recognized cardiotoxicity for their depolarization effects and
electrolyte depletion with increased excretion of potassium and
magnesium through the urine [54] and causes significant reductions in AV
and His-Purkinje conduction intervals, sinoatrial conduction time,
corrected sinus node recovery time, shortest atrial pacing interval
producing 1:1 AV conduction, for their effect of adenosine A1-receptor
antagonism in high concentration [21,55].
Patients receiving high dose steroids/corticosteroid therapy had
increased risk of developing AF, atrial flutter, supraventricular and
ventricular arrhythmias, and also increased risk of atherosclerosis,
diabetes mellitus, hypertension, left atrial enlargement and IHD
[56-58]. The other arrhythmogenic mechanism of AF is due high- dose
corticosteroids mediated potassium efflux via a direct effect on the
cell membrane and its profound peripheral vasodilatation and
anaphylactic reactions [58].
Acknowledgment
I express my innerfelt gratitude to Samuel Tadesse, Elsah Tegene and
Tewodros G/Mariam for their incredible support during the study. I also
want to thank Sr. Fantu, Sr. Worke, Sr. Saliya and Major G. for their
genuine corporation during data collection period. At last but not
least, my honoured thank go to all COPD patients who participated in the
study.
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