Impact of airflow limitation in chronic heart failure
Impact of airflow limitation in chronic heart failure
S. Bektas 0 1 3
F. M. E. Franssen 0 1 3
V. van Empel 0 1 3
N. Uszko-Lencer 0 1 3
J. Boyne 0 1 3
C. Knackstedt 0 1 3
H. P. Brunner-La Rocca 0 1 3
0 Department of Respiratory Medicine, Maastricht University Medical Center , Maastricht , The Netherlands
1 Department of Cardiology, Maastricht University Medical Center , Maastricht , The Netherlands
2 , Center of expertise for chronic organ failure , Horn , The Netherlands
3 Department of Research and Education , CIRO
Background Comorbidities are common in chronic heart failure (HF) patients, but diagnoses are often not based on objective testing. Chronic obstructive pulmonary disease (COPD) is an important comorbidity and often neglected because of shared symptoms and risk factors. Precise prevalence and consequences are not well known. Therefore, we investigated prevalence, pulmonary treatment, symptoms and quality of life (QOL) of COPD in patients with chronic HF. Methods 205 patients with stable HF for at least 1 month, aged above 50 years, were included from our outpatient cardiology clinic, irrespective of left ventricular ejection fraction. Patients performed post-bronchodilator spirometry, a six-minute walk test (6-MWT) and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). COPD was diagnosed according to GOLD criteria. Restrictive lung function was defined as FEV1/FVC ≥0.70 and FVC <80% of predicted value. The BODE and ADO index, risk scores in COPD patients, were calculated. Results Almost 40% fulfilled the criteria of COPD and 7% had restrictive lung disease, the latter being excluded from further analysis. Noteworthy, 63% of the COPD patients were undiagnosed and 8% of those without COPD used inhalation therapy. Patients with COPD had more shortness of breath despite little difference in HF severity and similar other comorbidities. KCCQ was significantly worse in COPD patients. The ADO and BODE indices were significantly different. Conclusion COPD is very common in unselected HF patients. It was often not diagnosed and many patients received treatment without being diagnosed with COPD. Presence of COPD worsens symptoms and negatively effects cardiac specific QOL.
Prevalence; Chronic obstructive pulmonary disease; Chronic heart failure; Diagnosis; Quality of life
Heart failure (HF) and chronic obstructive pulmonary
disease (COPD) are amongst the leading causes of morbidity
and mortality in Western countries. Until recently, COPD
and HF have mostly been studied individually, but during
the last years, the awareness of the interaction of both
diseases has grown. Studies showed that HF and COPD
frequently coincide, but precise epidemiologic data are
lacking. In fact, the reported prevalence of COPD in HF patients
varied substantially between 9–52% [1–4]. In part, this may
be caused by the lack of systematic lung function testing.
Diagnosing COPD is challenging, especially in patients
with HF. Not only do the two diseases share major
symptoms such as dyspnoea and fatigue, they also have
common etiological factors such as smoking and ageing [5–8].
Consequently, under- and over-diagnosing COPD in HF
patients are common [9–12]. Also from a therapeutic and
prognostic perspective, the coincidence of COPD and HF
is relevant. Many patients with HF are treated with
inhalation therapy, although no proper diagnosis of COPD has
been made . Accordingly, patients may be treated
inadequately, but the extent of this has not yet been properly
addressed. Since both diseases result in significantly reduced
quality of life and mortality, proper diagnosis, and
consequently treatment, may result in considerably improved
well-being of these patients [13–15].
Therefore, this study aimed to address those clinically
important shortcomings by investigating consecutive
patients diagnosed with and treated for chronic HF,
irrespective of left ventricular ejection fraction (LVEF), with respect
to the prevalence of COPD, treatment and the clinical
consequences thereof. Moreover, we aimed to identify patients
at risk for airflow limitation compatible with COPD.
Study design and participants
Consecutive patients visiting the outpatient HF clinic of
the Maastricht University Medical Centre (the Netherlands)
were screened for inclusion in this cross-sectional
observational study between October 2012 and November 2013
and were asked to participate in this study. Inclusion
criteria were documented HF based on prevailing European
Society of Cardiology guidelines  with left
ventricular dysfunction (LVD), irrespective of LVEF, age above 50
years and clinically stable condition for at least one month.
Patients who were not able to cooperate or in whom
spirometry was clinically contraindicated (detached retina, active
tuberculosis, resting pulse >120/min) were excluded. Other
exclusion criteria were recent surgery, recent myocardial
infarction (<1 month), lower respiratory tract infection or
pneumothorax within the last 2 months or stroke within the
last 12 months. The study was approved by the local ethics
committee. All patients provided written informed consent
prior to enrolment.
Measurements and data collection
The following clinical characteristics and symptoms were
extracted from the patient charts: age, gender, cause of
HF, other cardiovascular diseases, co-morbidities,
cardiovascular risk factors (diabetes, hypertension,
hypercholesterolaemia, smoking), healthcare utilisation in the past year,
NYHA class, weight and height, hip/waist circumference,
blood pressure, heart rate, ECG (rhythm, QRS complex
duration), currently used medication, in particular cardiac and
pulmonary medication in detail, recent antibiotic and
glucocorticosteroid use for respiratory symptoms/infections.
Also, (non-invasive) O2-saturation at rest was measured.
Two years after the inclusion of the first patient, medical
charts were retrospectively reviewed to determine all-cause
Lung function was measured in all patients after 200 μg of
salbutamol was given. Spirometry (Masterscreen, Jaeger,
Würzburg, Germany) was performed by fully trained
respiratory technicians according to ERS standards for
acceptability and reproducibility . Airflow limitation,
compatible with COPD, was defined according to the Global
initiative for Obstructive Lung Disease (GOLD) report 
as a ratio between forced exhaled volume in the first
second (FEV1) and forced vital capacity (FVC) less than 0.70
after bronchodilatation. According to GOLD, the severity of
airflow limitation was staged as mild, moderate, severe and
very severe if percent predicted FEV1 was >80%, 50–80%,
30–50%, or <30%, respectively . Patients fulfilling the
diagnostic criteria for COPD, were subsequently stratified
according to symptoms and future risk . For this
classification, COPD Assessment Test (CAT) scores were used as
the preferred symptom measure . Restrictive lung
disease was defined as post-bronchodilator FEV1/FVC ≥0.70
and FVC <80% of predicted, while normal lung function
was defined as neither airflow limitation nor restrictive lung
disease. A six-minute walk test (6-MWT) was carried out
according to international standards .
We collected the results of comprehensive standardised
echocardiographic (Philips IE33) examination performed
within 6 months prior to study enrolment. If no recent
echocardiography was available, it was repeated for this
study. Assessment included left ventricular end-systolic
and end-diastolic dimensions and function, dimensions
of atria, right ventricle dimension and function, valvular
functions, and estimate of systolic pulmonary arterial
pressure (gradient across tricuspid valve, as well as dimension
and variation of vena cava inferior). HF was split into
two groups, based on the LVEF. Thus, HF with preserved
LVEF (HFpEF) has been defined as the presence of typical
HF signs and symptoms, evidence of diastolic dysfunction
(abnormal LV relaxation or diastolic stiffness) and presence
of normal or only mildly abnormal LV systolic function,
i. e., LVEF of more than 50%. Patients with HF signs and
symptoms and LVEF of <50% were defined as having HF
with reduced LVEF (HFrEF) .
Normal lungfunc on
Fig. 1 Distribution of new GOLD classification A–D in heart failure
patients. (COPD chronic obstructive pulmonary disease, GOLD Global
initiative for chronic Obstructive Lung Disease)
Patients completed the Kansas City Cardiomyopathy Ques
tionnaire (KCCQ) , a 23-item questionnaire that
quantifies physical limitations, symptoms, self-efficacy, social
interference and quality of life. Dyspnoea was quantified
by the modified Medical Research Council (mMRC) scale
. Health status was assessed with the CAT, which is
a COPD-specific health status questionnaire . In
addition, Body mass index, airflow Obstruction, Dyspnoea, and
Exercise capacity (BODE)  and Age, Dyspnoea, airflow
Obstruction (ADO)  indices were calculated. Where the
distance walked in six minutes (6-MWT) was not known,
350 m was used to calculate the score. Where mMRC was
missing, NYHA class was used.
Descriptive data are presented as mean (±standard deviation
– SD), frequencies (%) or median (interquartile range –
IQR), as appropriate. Baseline characteristics of patients
with and without COPD were compared using independent
t-test or Mann-Whitney U test for continuous variables and
Chi-square or Fisher’s exact test for categorical variables,
as appropriate. Survival analyses were done using
KaplanMeier curves and groups were compared using the log-rank
test. A two-sided p-value of less than 0.05 was considered as
statistically significant. We used the commercially available
statistical package SPSS v 22.0 (IBM) for analyses.
A total of 586 patients were screened. Of these, 205 HF
patients volunteered to participate in this study. Six patients
did not complete a lung function test and were excluded for
further analysis. Of the remaining 199 patients, 13 patients
(7%) had restrictive lung disease and were not analysed
further (Fig. 1).
The demographic and clinical characteristics are shown
in Table 1. The patients had an overall mean age of 76
years, median LVEF of 44% and approximately 70% of
the participants were male. The mean ejection fraction for
HFrEF patients was 37%. Thirty percent of the patients had
HFpEF. Approximately half of the patients had mild
symptoms (NYHA class II) and 50% had an ischaemic aetiology
of HF. Other most common causes of HF were dilated
cardiomyopathy (19%) and hypertensive heart disease (18%).
Most patients were former or non-smokers.
Of the 186 patients without restrictive lung disease, 68
(37%) fulfilled the criteria of COPD. According to the
traditional GOLD classification, 29 (15%) patients had mild,
31 (16%) moderate and 8 (4%) severe disease, while no
patients had very severe COPD. When the updated GOLD
assessment was applied, most COPD patients were
categorised as GOLD B (Fig. 1). The prevalence of COPD did
not differ between men and women.
Importantly, 43 (63%) patients were previously
undiagnosed with COPD, whereas 3 of 118 patients (2.5%) who
did not have significant airflow limitation had received the
diagnosis of COPD previously. In addition, 8% of the
patients used pulmonary medication without a proper
diagnosis of COPD.
Patients with COPD had more symptoms of dyspnoea
as compared to those having HF only. Systolic blood
pressure and saturation differed significantly. The number of
co-morbidities was similar in both groups. The proportion
of patients with a previous diagnosis of asthma was not
significantly different between HF patients with and
without COPD. The distance walked during the 6-MWT did not
differ significantly (Table 2).
The medication used in both groups was similar, except
for the inhalation therapy at baseline, which was more
frequently used in the COPD patients (Table 1).
Quality of life and survival
The difference in the CAT score between HF patients with
or without COPD failed to reach statistical significance
(Table 2). The overall KCCQ scores were significantly
worse in the COPD group (p = 0.005) as summarised in
Table 3. The following domains were significantly worse
in the COPD group: physical limitation, symptom severity
and symptom stability. The other domains did not
significantly differ between patients with and without COPD.
Symptoms and clinical findings
O2 saturation (n = 134)
History of COPD I–IV
History of asthma
Exacerbation last year
All (n = 186)
Baseline characteristics of the heart failure patients with or without COPD
No COPD (n = 118)
COPD (n = 68)
Data are presented as number (%), mean (±SD) and median [IQR], unless specified otherwise. P-values below 0.05 in bold
BMI body mass index, CAD coronary artery disease, DCM dilated cardiomyopathy, HHD hypertensive heart disease, NYHA New York Heart
Association class, CVA cerebrovascular accident, TIA transient ischemic attack, PAD peripheral arterial disease, NT-proBNP N-terminal pro-brain
natriuretic peptide, COPD chronic obstructive pulmonary disease, FVC forced vital capacity, FEV1 Forced expiratory volume in 1 s, ACE-I
angiotensin converting enzyme inhibitor, ARB angiotensin receptor blocker, β-blockers beta-adrenergic blocking agents
COPD (n = 68)
Table 2 Dyspnoea assessment and 6-minute walk test in heart failure patients with or without COPD
All (n = 186) No COPD (n = 118) COPD (n = 68)
Data are presented as number and median [IQR], unless specified otherwise. P-values below 0.05 in bold
CAT COPD assessment test, 6-MWT six-minute walk test, mMRC modified Medical Research Council scale
Table 3 Quality of life in heart failure patients with or without COPD
QOL Overall (n = 186) No COPD (n = 118)
Mean (±SD), median [IQR]. P-values below 0.05 in bold
COPD chronic obstructive pulmonary disease, ADO Age, Dyspnoea and airflow Obstruction, BODE Body-mass index, airflow Obstruction,
Dyspnoea, and Exercise capacity, QOL quality of life, KCCQ Kansas City Cardiomyopathy Questionnaire
The ADO and BODE index were significantly different
between the two groups (Table 3).
Survival did not differ significantly between HF patients
with COPD and without COPD (p = 0.54) (Fig. 2).
This study showed a high prevalence of COPD in HF
patients, which was comparable for HFrEF and HFpEF.
Noteworthy, HF patients with concomitant COPD experienced
significantly more symptoms of dyspnoea and had worse
quality of life compared to those without COPD, despite
no evidence of differences in severity of HF. This may be
of particular clinical importance as underdetection of COPD
was common. On the other hand, some patients were treated
with pulmonary medication without a proper diagnosis.
Prevalence of COPD in heart failure
In previous studies, the prevalence of COPD varied widely
from 9 to 56% in patients with chronic HF, being on
average between 20 and 30% [12, 25–27]. Most studies were
retrospective and included decompensated or hospitalised
HF patients [8, 11, 12, 25–27]. Studies in stable chronic
HF patients are, however, relatively scarce. Valk et al. ,
reported COPD prevalence of 28% in 106 primary care
patients. Boschetto et al.  reported a prevalence of 30% in
118 predominantly male, ambulatory HF patients.
Masceranhas et al.  included 186 HFrEF patients
retrospectively and reported a COPD prevalence rate of 40%. The
variation in prevalence rates may depend on factors such as
population, study design, inclusion criteria and used
diagnostics . In particular, most studies did not
systematically perform lung function testing and based the
diagnosis on medical history alone. In the current study, state of
the art spirometry was performed in all HF patients. Given
the significant proportion of underdiagnosis of COPD, this
very likely explains the somewhat higher prevalence in this
study. Moreover, the prevalence of COPD in HF patients
increases with age until approximately 75 years [28, 29].
Thus, the mean age of >75 years in this study may have
contributed to the observed prevalence.
HF itself can cause a reduction of about 20% in FEV1
and FVC . Therefore, some studies recommend the use
of the individual lower limit of normal (LLN), instead of
the GOLD classification, to define COPD to prevent
overdiagnosis of COPD in the elderly HF patients [31–33].
Fig. 2 Kaplan-Meier survival plot in heart failure patients with
or without COPD. (COPD chronic obstructive pulmonary disease,
GOLD Global initiative for chronic Obstructive Lung Disease, HF heart
failure, HR hazard ratio (95% confidence interval), p-value derived
from log-rank test)
However, in stable, not volume overloaded patients, the
ratio FEV1/FVC is almost similarly impaired, thus the ratio
FEV1/FVC is not affected prominently when spirometry
is performed in a stable condition of the disease [30, 33].
This study included only stable HF patients;
overdiagnosing COPD by using the fixed FEV1/FVC ratio proposed
by GOLD in this study is therefore very unlikely [30, 34,
35]. Furthermore, the current guidelines acknowledge the
limitations of the current GOLD-COPD classification, but
appropriate alternatives are lacking .
Prevalence of COPD in HF patients with HFpEF was
reported to be higher in comparison to HF with HFrEF
. This study did not confirm such a difference
between patients with HFpEF and HFrEF. In fact, patients
with preserved ejection fraction even tended to have less
concomitant COPD. There are several reasons that could
explain this discrepancy. Thus, most of the previous reports
were retrospective, did not use proper testing, were
predominantly performed in hospitalised patients and cut-off
regarding ejection fraction was not uniform [36–42].
Moreover, inclusion of HFpEF patients who actually have HF
is certainly challenging and misdiagnosis exists [43, 44].
Thus, reliable estimates of COPD prevalence in
representative stable HFpEF patients are still lacking . Therefore,
this study gives important insight in the COPD prevalence
in the HFpEF population in comparison to other studies.
Given the results of this study, showing that diagnosis of
COPD is often missed or performed without proper testing,
and the same is true for HFpEF, it may be speculated that
some COPD patients may be misdiagnosed as HFpEF (and
vice versa) in previous cohorts, highlighting the need for
proper diagnostics, particularly in patients with suspicion
Impact on symptoms and quality of life
The presence of COPD appears not only to worsen
dyspnoea, but also negatively affect cardiac specific quality
of life, as seen by the results of the KCCQ. On the other
hand, the presence of COPD in HF patients did not
negatively affect pulmonary specific health status, as assessed
by the CAT questionnaire. Still, there was a strong trend
which just failed to reach statistical significance, possibly
due to less power as a result of missing values.
Unfortunately, there is no specific questionnaire for patients with
HF and concomitant COPD. In this regard, there is room
to investigate and compare which questionnaire is suited
best for such patients, or to develop a new questionnaire
that specifically addressing symptoms and quality of life
for patients suffering from both HF and COPD.
Despite having more symptoms, the functional status
was not different between the two groups as assessed by
the 6MWT . This contrast with a previous study and
the discrepancy cannot easily be explained. The average
distance walked in this study indicates mild to moderate
limitation in functional capacity, probably primarily due to
Impact on prognosis
Even though the effect on survival is negligible, current
treatment of COPD generates symptom relief and improves
quality of life [45, 46]. Therefore, it may be expected that
proper treatment of COPD may result in improvement of
symptoms and quality of life. Still, it needs to be
prospectively tested if this really is the case. On the other hand,
up to now it is unknown which specific COPD treatment
is the best in HF patients. Advantages of HF medication in
comorbid COPD patients on survival are well established,
but the other way around is not that well established.
Caution is needed with some inhalation therapy in HF patients
[47–49]. Therefore, safety and efficacy of various COPD
drugs needs to be tested in appropriate trials. In addition,
cessation of unnecessary treatment in patients not having
COPD is of utmost importance. In this study, some patients
received pulmonary medication without a proper
diagnosis. Finally, survival was not adversely affected by COPD
in this study. However, the study was too small to address
this question sufficiently. Previous reports suggested some
impact, but results were not uniform. Again,
inhomogeneous criteria for diagnosis and differences in treatment
may explain such discrepancies, further stressing the need
of prospective testing of best management of these patients
in a large prospective trial.
Strengths and limitations
A strength of this study is the inclusion of a representative
group of stable chronic HF patients with both preserved
and reduced ejection fraction, independent of their
smoking status. Importantly, all patients underwent both lung
function testing and had echocardiography. Therefore,
diagnosis of both COPD and HF was accurate. A limitation
is the relatively limited sample size. Moreover, some
exclusion criteria applied and not all patients gave informed
consent for participation. Therefore, we can exclude some
selection bias. The relatively good prognosis in our cohort
shows that we included stable HF patients and results might
be different in less stable patients or patients with more
In conclusion, this study demonstrated that 40% of HF
patients may have concomitant pulmonary disease,
predominantly mild to severe COPD. Importantly, these patients
had more severe symptoms of dyspnoea and worse
quality of life than those without COPD. Many patients with
COPD were undetected and some were treated for
pulmonary disease without proper diagnosis, or received the
wrong treatment. Thus, the findings of this study underline
the importance of systematically identifying patients with
COPD who are diagnosed with HF.
Funding This work was supported by an unrestricted research grant
from GlaxoSmithKline Europe.
Conflict of interest S. Bektas, F.M.E. Franssen, V. van Empel,
N. Uszko-Lencer, J. Boyne, C. Knackstedt and H.P Brunner-La Rocca
declare that they has no competing interests.
Open Access This article is distributed under the terms of the
Creative Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted
use, distribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were
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