Coexisting chronic obstructive pulmonary disease and heart

failure: implications for treatment, course and mortality

Joana Mascarenhasa,b, Ana Azevedoa,b,c and Paulo Bettencourta,b
a
b
Servico de Medicina Interna, Hospital S. Joao,
Unidade de Investigacao e Desenvolvimento
Cardiovascular do Porto and cServico de Higiene e
Epidemiologia, Faculdade de Medicina da Universidade
do Porto, Instituto de Saude Publica da Universidade
do Porto (ISPUP), Porto, Portugal
Correspondence to Dr Joana Mascarenhas, Servico de
Medicina Interna, Hospital S. Joao, Alameda Prof.
Hernani Monteiro, 4200-319 Porto, Portugal
Tel: +351 966104032; fax: +351 225513653;
e-mail: joanamaspinto@gmail.com
Current Opinion in Pulmonary Medicine 2010,
16:106111
Purpose of review
Chronic obstructive pulmonary disease (COPD) and heart failure are prevalent
comorbidities affecting a huge proportion of the world population, responsible for
significant morbidity and mortality. Their coexistence is more frequent than previously
recognized and poses important diagnostic and therapeutic challenges. Prognosis of
patients with concurrent heart failure and COPD has not been comprehensively
addressed. With this review, we intend to emphasize the diagnosis and prognosis
implications of the two coexisting conditions and to highlight the therapeutic constraints
posed by the combination.
Recent findings
Progressively, more attention has been given to the interplay between COPD and heart
failure. The combination is frequent, but largely unrecognized due to overlapping clinical
manifestations. Patients presenting with both conditions seem to have an ominous
course. Despite the overwhelming evidence supporting cardioselective b-blockade
safety and tolerability in COPD patients, b-blockers are underprescribed to heart failure
patients with concomitant COPD.
Summary
COPD and heart failure coexistence is often overlooked. COPD diagnosis can remain
unsuspected in heart failure patients due to similar symptoms. Although b-blockers are
well tolerated in COPD patients, they are overall less prescribed in this challenging
population. COPD, at least at severe degrees of airflow obstruction, predicts a worse
prognosis in heart failure patients.

Keywords
b-blockers, chronic obstructive pulmonary disease, heart failure, prognosis

Curr Opin Pulm Med 16:106111

2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
1070-5287

agents are considered the cornerstone of systolic heart

Introduction
Heart failure and chronic obstructive pulmonary disease
(COPD) are major public health epidemics, with increas-
ing prevalence [1,2,3]. Although both conditions
have been extensively studied separately, clinicians
often fail to recognize one syndrome in the presence
of the other, mainly due to the similarities in clinical
presentation and additionally due to scarcity of reports
specifically addressing the combination [4]. According to
available evidence, COPD and heart failure often coex-
ist, and the prevalence of the combination is variable,
depending on the population studied (community, out-
patient or hospitalized) and on the diagnostic criteria
applied [4,5]. The coexistence of the two conditions is
further supported by shared risk factors, notably age and
smoking [1,5,6].
Since the publication of several trials demonstrating the
efficacy and the survival benefits of b-blockers, these
1070-5287 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
failure management [79]. Although extensive evidence
concerning safety of selective b-1 blockade in respiratory
disease has accumulated [10,11], COPD is commonly
advocated as the principal cause for nonadherence to
heart failure therapeutic guidelines because it is gener-
ally perceived as a contraindication to b-blockers use
[12,13]. Indeed, patients with coexisting heart failure
and COPD are often deprived of the long-term benefits
of this intervention [12,14]. Apart from these therapeutic
issues, the prognosis of patients with concomitant heart
failure and COPD is not completely understood. In an
increasing number of studies [15,16,17], COPD has
been found to adversely impact on prognosis of heart
failure patients, being an independent predictor of
mortality and hospitalization.
The present review focuses on the therapeutic dilemmas
and prognostic impact of coexisting COPD and heart
failure and outlines the diagnostic challenges presented
DOI:10.1097/MCP.0b013e328335dc90

by the combination. The prevalence of the two coexisting
syndromes will be addressed briefly.
Coexisting chronic obstructive pulmonary
disease and heart failure: epidemiology and
the interplay
There are several observations reporting a high rate of
coexistence of COPD and heart failure, particularly in
the elderly population [1,2,3,5]. The prevalence
of heart failure in COPD patients varies between 7.2
and 20.9% [1821], with the highest estimates coming
from studies that have used standardized heart failure
diagnostic criteria [20,21]. Considerable variation of
COPD prevalence in patients with heart failure is also
found across studies, with estimates ranging from
approximately 10.0 to 39.0% [2226,27,28]. In these
investigations, the diagnosis of COPD was almost
always based on clinical data or on self-reported infor-
mation [2226], with the exception of two studies
[27,28] that have evaluated the prevalence of physio-
logically defined disease according to Global Initiative
for Chronic Obstructive Lung Disease (GOLD)
criteria. In light of previous observations showing poor
agreement between self-reported and objectively
defined COPD [29], the higher prevalence of COPD
observed in these two studies, 39.2% in a cohort of
elderly stable patients with chronic heart failure and
35% in patients consecutively admitted with heart
failure, is not surprising. Noteworthy, using self-
reported information may leave COPD diagnosis unre-
vealed in a considerable number of heart failure
patients [28] or, alternatively, may label with the
diagnosis of COPD patients not fulfilling the criteria
for airflow obstruction [30]. In patients with preserved
left ventricular ejection fraction (LVEF), some degree
of misdiagnosis probably occurs, and the finding of a
higher prevalence of COPD can be at least partially
explained by the inaccurate attribution of heart failure
diagnosis to patients who actually have COPD [28]. At
last, given the strict selection of patients included in
heart failure trials, the reported prevalence of COPD in
this setting is lower than in population-based studies
(713%, with only one study reporting a prevalence of
23%), reflecting a selection bias [5,3134].
In order to explain the high rate of coexistence of these
two a etiologically distinct conditions, several plausible
theories have been proposed, namely, the sharing of
smoking as a major risk factor [5] and the association
of low-grade systemic inflammation present in COPD
patients with the development and progression of ath-
erosclerosis [35,36]. Regardless of the potential mech-
anisms underlying the combination, current estimates of
COPD and heart failure concurrence are worrisome and
underscore the need for greater physicians awareness
Coexisting COPD and heart failure Mascarenhas et al. 107
concerning the diagnosis of the two coexisting syn-
dromes.
Diagnostic challenges presented by the
chronic obstructive pulmonary disease/heart
failure combination
The diagnostic assessment of concomitant COPD and
heart failure is demanding and requires a high level of
expertise from the involved physician. First, both con-
ditions usually present with similar nonspecific symp-
toms and signs (exertion dyspnoea, functional disability,
nocturnal cough, peripheral oedema, pulmonary crackles
and jugular venous distension, among others), and there
is no distinctive feature exclusive to each of them.
Second, these characteristic clinical features are fre-
quently masked by or attributed to additional comorbid-
ities [37], present mainly in the elderly [3]. Moreover,
the absence of an objective definition of heart failure,
whose diagnosis requires the typical clinical picture as
well as objective evidence of cardiac dysfunction [2],
can compromise the correct recognition of this entity
when echocardiography is not available, as other con-
ditions can mimic the clinical syndrome of heart failure
[38].
To assist in the diagnosis of each disease, a number of
complementary tests can be performed. However, the
coexistence of COPD and heart failure can interfere with
the quality of the information obtained. Although a
normal electrocardiogram is useful to exclude heart fail-
ure, this tool lacks specificity to undoubtedly assert that
diagnosis because abnormalities found frequently over-
lap with those seen in other conditions, including COPD
[39]. The interpretation of chest radiography may be
misleading because chest hyperinflation present in
COPD patients can mask an increased cardiothoracic
ratio and right ventricular enlargement can obscure left
ventricular dilation [40]. Also, whereas extra shadows
commonly seen in lung disease can suggest spurious
pulmonary oedema, the remodelling of pulmonary vas-
cular bed may hide the typical alveolar pattern found in
acute heart failure [5,40]. Poor acoustic window caused
by pulmonary air trapping may hinder accurate echocar-
diographic assessment of LVEF in 1035% of COPD
patients, particularly in those with more severe degrees of
airflow obstruction [41,42]. To overcome this limitation,
the use of cardiac MRI (CMRI) is currently being advo-
cated as an alternative. Apart from providing accurate and
reproducible measurements of left ventricular volumes
and LVEF that are not affected by lung hyperinflation,
this technique is also valuable in the correct evaluation of
right ventricular volume and function [43]. The useful-
ness of natriuretic peptides to reliably diagnose or rule
out heart failure as the cause of acute dyspnoea is well
established in patients without COPD [44]. Although at
108 Obstructive, occupational and environmental diseases
higher thresholds, natriuretic peptides remain accurate in
the diagnosis of heart failure in COPD patients, mainly
during acute exacerbation [45]. Finally, notwithstanding
restrictive defects that are commonly encountered in
stable heart failure patients, the finding of airflow
obstruction should not necessarily be attributed to coex-
istent COPD in the acute setting, as an obstructive
pattern is frequently found in decompensated heart
failure [5].
Therapeutic dilemmas of coexisting chronic
obstructive pulmonary disease and heart
failure
Despite the publication and regular update of guidelines
to assist physicians on the management of COPD and
heart failure [1,2], the coexistence of both diseases
creates important therapeutic dilemmas that lead to
suboptimal treatment of patients. In fact, several surveys
conducted in order to address clinicians compliance with
guidelines have consistently shown underutilization of
heart failure evidence-based treatment, namely b-block-
ers, and prescription of lower than recommended dosages
of these agents, especially in patients with concurrent
COPD [12,14,46]. The available evidence regarding
heart failure treatment derives from randomized clinical
trials from which COPD patients have been frequently
excluded [5]. Therefore, the best management strategy
to treat patients with both conditions is uncertain, as it is
based on retrospective studies and on subgroup analysis
of heart failure trials [47].
b-blockers have been shown to improve heart failure
prognosis across the entire spectrum of disease severity
[79], being recommended in all patients with systolic
dysfunction [2]. Regardless of their unequivocal mor-
bidity and mortality benefits, these agents remain under-
used and are frequently withdrawn in heart failure
patients with concomitant COPD due to fear of precipi-
tating bronchospasm [12]. In a recently published Euro-
pean survey, COPD was the most powerful predictor of
b-blockers underprescription in heart failure patients
and was identified as a cause of poor target dose achieve-
ment [46]. The same report pointed out that, even
though b-blocker prescription increased significantly
after the publication of updated guidelines in 2005, the
percentage of heart failure patients on these agents is still
far from ideal [46]. According to current evidence, stable
COPD should not be considered a valid contraindication
to b-blocker therapy because these agents have proved to
be safe and generally well tolerated in patients with
pulmonary disease [11,48]. In brief, selective b1 blockade
does not significantly affect short-term pulmonary func-
tion and also does not attenuate b2-induced broncho-
dilation [49]. As a result, selective b-1-blocking agents
can be safely used in all heart failure patients with
respiratory disease [49,50], even in those with reversible
obstruction [11]. Although nonselective b-blockade com-
bined with a-blockade is also well tolerated in COPD
patients without reactive airway component, the safety
profile of these drugs is not as well established in patients
with reactive airway disease [10,51]. Consistent with
these data, the recommendations of Heart Failure
Society of America advocate b-blocker therapy in all
patients with coexistent COPD and heart failure [52].
However, a recently published randomized controlled
study [53] found a reduction in forced expiratory
volume in 1 s (FEV1), but not impaired reversibility or
quality of life, after initiation of bisoprolol in heart failure
patients with concomitant moderate-to-severe COPD.
These apparent conflicting findings underscore the need
of additional randomized controlled trials addressing the
real impact of b-blocker therapy in heart failure patients
with concurrent COPD. Although the controversy regard-
ing this issue is ongoing, it seems advisable to use these
agents in patients with both conditions, provided that
adverse effects are regularly monitored.
Additional therapeutic modalities used in heart failure
may also carry particular problems in COPD patients.
The metabolic alkalosis caused by intensive diuretic
therapy may interfere with the respiratory drive of COPD
patients, causing hypoventilation with subsequent wor-
sening of hypercapnia, although this theoretical effect is
rarely reported at standard doses [4]. A potential
beneficial role to angiotensin-converting enzyme
(ACE) inhibitors and angiotensin-II receptor blockers
(ARBs) has been claimed in heart failure patients with
concurrent COPD due to their effects in decreasing
pulmonary inflammation and vascular constriction [54].
Finally, concerns regarding the use of inhaled broncho-
dilators [anticholinergics and b2-adrenoreceptor (B2R)
agonists] in COPD patients with concomitant heart fail-
ure have always been manifested by physicians. Whereas,
till the present, no adverse effect has been reported in
heart failure patients treated with anticholinergics [4,55],
short-acting B2R agonists were found to increase the risk
of mortality and heart failure exacerbations in a restricted
number of studies [56,57]. These agents were pointed to
as potentially deleterious for cardiac muscle because they
can increase myocardial oxygen consumption through the
induction of tachycardia [56,58]. Since the publication of
a recent randomized study [59] that failed to show
increased occurrence of adverse cardiovascular events
with the use of long-acting B2R agonists, these agents
are the preferred treatment option in the majority of
COPD patients, namely, in those with cardiovascular
comorbidities.
The analysis of these data, in addition to guidelines on
the pharmacological approach of heart failure patients
 Coexisting COPD and heart failure Mascarenhas et al. 109

with COPD, suggests that patients with both conditions Figure 1 KaplanMeier event-free survival curves according to
should be able to profit from the therapies known to chronic obstructive pulmonary disease coexistence
improve prognosis of heart failure patients.

1.0 ++
+++
Prognostic implications of concurrent chronic +
+
obstructive pulmonary disease and heart +++
++
failure 0.8
++++
++
++ +
The association between COPD and several cardiovas- ++ +
+ ++
++
cular endpoints has been previously suggested [18,19]. +
+
+ +
+
++ + ++ +
COPD patients, notably those with concomitant heart + ++ + + ++
0.6
failure [19], were found to be at an increased risk for +
+
hospitalization and death due to cardiovascular diseases, P = 0.16
++
+
independently of the presence of traditional cardiovas-
cular risk factors [19,60]. In patients with heart failure, 0.4

the presence of noncardiac comorbidities, including

COPD, has been strongly associated with adverse
COPD
clinical outcomes [16,25,31,37]. The prognostic impact 0.2
No
of COPD was observed in patients with both preserved Yes
and reduced LVEF [15]. A recently published review
[5] concluded that, across several studies using multi- 0.0
variable models, COPD was consistently an indepen-
dent predictor of death and hospitalization in patients 0.00 200.00 400.00 600.00 800.00

with heart failure. Its coexistence prolongs time to Time (days)

discharge, promotes frequent readmissions and incurs
significant additional costs in patients hospitalized due COPD, chronic obstructive pulmonary disease. Reproduced with per-
mission from [27].
to decompensated heart failure. The specific cause of
death was ascertained only in one study [32], in which
COPD was found to independently predict noncardiac
mortality and hospitalizations but not cardiovascular
events.
Figure 2 KaplanMeier curves comparing event-free survival
according to chronic obstructive pulmonary disease stages
Contrasting with these observations, we found, in a
cohort of elderly stable patients with chronic heart failure
[27], that only severe COPD (stages III and IV as
defined by GOLD criteria) was associated with an 1.0 ++
+++
+ +
adverse course (Figs 1 and 2). Differences in our results
++ ++
can be partially attributed to the adopted COPD defi- + +++
+ +++
0.8 +
nition because the diagnosis of COPD based on objective + + + +
+ ++ +
+ ++
measurements of respiratory function identifies patients ++ + +++
+
++ +
across all degrees of disease severity, even those mini- 0.6 + ++
+
+
mally symptomatic who generally do not seek medical + ++
attention. +
0.4
GOLD stages +
The mechanisms underlying increased cardiovascular 0 0.036
I
risk in patients with COPD are yet to be completely 0.2 II
understood [3]. Although impaired pulmonary function, III/IV
as expressed by reduced FEV1, has been shown to be a
strong independent predictor of cardiovascular mortality 0.0

[61], the relationship between COPD and cardiovascular 0.00 200.00 400.00 600.00 800.00
events remains unclear. Recent investigations have Time (days)
focused on the interplay between systemic inflammation
and airflow obstruction as a potential explanation for the Stage I: HR 1.06 (95% CI 0.472.37); stage II: HR 1.31 (95% CI 0.72
development of cardiac injury in COPD patients [35]. 2.38); stages III and IV: HR 2.10 (95% CI 1.054.22). CI, confidence
Apart from the mechanism(s) involved, cardiovascular interval; GOLD, Global Initiative for Chronic Obstructive Lung Disease;
HR, hazard ratio. Reproduced with permission from [27].
conditions are the leading cause of morbidity and
110 Obstructive, occupational and environmental diseases
mortality in COPD patients, independently of other risk
factors including smoking [10].
The prognostic implications of COPD in heart failure
patients and vice-versa remain, however, largely unde-
fined due to the limited number of studies specifically
addressing the prognosis of patients presenting with both
diseases and due to the short follow-up of the majority of
the existing reports.
Conclusion
The coexistence of COPD and heart failure is frequent,
but commonly ignored. The diagnosis of one condition
in the presence of the other is challenging and requires
objective evidence of pulmonary and cardiac dysfunc-
tion, apart from the appropriate clinical picture.
Although long-term effects of b-blockers need to be
further assessed in COPD patients, these agents are
currently recommended in all heart failure patients
with concurrent COPD. Despite this, prescription
rates remain disappointingly low mainly because of
concerns related to bronchospasm. It is generally
acknowledged that COPD adversely affects heart
failure prognosis, although more conclusive studies
are still needed.
Considering the expanding mortality and the profound
impact on quality of life and performance status imposed
by each disease, it is crucial to diagnose these two
coexistent conditions and to establish a management
strategy that simultaneously addresses both comorbid-
ities in order to alleviate symptoms, delay progression and
improve prognosis.
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:
 of special interest
 of outstanding interest
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