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Chronic obstructive pulmonary disease: Pathophysiological impact on heart

failure in real clinical situation

Article  in  Journal of Cardiology · June 2014

DOI: 10.1016/j.jjcc.2014.05.003

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 Journal of Cardiology 64 (2014) 250–252
Contents lists available at ScienceDirect
Journal of Cardiology
journal homepage: www.elsevier.com/locate/jjcc
Editorial
Chronic obstructive pulmonary disease: Pathophysiological impact on
heart failure in real clinical situation
Keywords:
Heart failure
Chronic obstructive pulmonary disease
Systemic inflammation
Prognosis
Beta-adrenergic blocker
Chronic obstructive pulmonary disease (COPD) is a global
epidemic and characterized by airway limitation accompanied by
chronic inflammation [1]. Heart failure (HF) is also a global
epidemic and dyspnea on exertion is the overlapping symptom
with COPD [2]. Both conditions cause significant mortality. Clinical
assessment of the combination of COPD and HF is sometimes
difficult because both share the same pathogenic mechanism.
Because of the complex overlapping pathophysiology, there are
unresolved issues concerning the details of prevalence, prognostic
impact, pathophysiology, and appropriate selection of therapy
especially with regard to the use of beta-adrenergic agonists or
blockers. Yoshihisa et al. [3] have prospectively investigated the
clinical impact of coexisting COPD in hospitalized HF patients and
shed further light on our knowledge.
The diagnosis of concurrent COPD with HF is often difficult
for cardiologists, and vice versa is true for pulmonologists [2],
especially at the acute exacerbation phase of either condition. In
the acute hypervolemic stage of HF, lung congestion causes
transient airway obstruction. Most studies of the COPD and HF
combination are retrospective and the diagnoses were not based
on Global Initiative for Chronic Obstructive Lung Disease (GOLD)
criteria [4]. Therefore, there have been few reports on the
frequency of HF comorbidity with COPD. Yoshihisa et al. [3] have
systematically performed lung function tests and measured the
forced expiratory volume in the first second (FEV1) values in 378
consecutive hospitalized HF patients at the stable stage. They
demonstrated that the prevalence of COPD was 28% in HF
patients. It is surprising that only 6% of Japanese HF patients
have moderate COPD (80% > FEV1 > 50%), and that the remain-
ing 22% had COPD that was mild (FEV1 > 80% of expected), and
none of them had severe or very severe COPD [3]. The
prevalence of moderate COPD in HF was apparently less than
DOI of original article: http://dx.doi.org/10.1016/j.jjcc.2014.02.003
http://dx.doi.org/10.1016/j.jjcc.2014.05.003
0914-5087/ß 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
that in a recently reported study in Italy with a similar
diagnostic protocol [5], in which mild COPD was present in
6.5%, moderate in 17.9%, severe in 12.4%, and very severe in 0.5%
among 201 HF patients over 60 years. The difference may be due
to, at least in part, the low percentage of smokers, 46% in the
Japanese study and 52% in the Italian study. The lack of severe or
very severe COPD patients in this Japanese HF registry may be
due to selection bias, i.e. severe COPD patients who suffered
from right HF or the so-called ‘‘cor-pulmonale,’’ which may be
managed by pulmonologists, not by cardiologists in Japan.
In patients with HF, COPD is an independent predictor of death
and hospitalization in most published articles [6]; however, in a
recent objective diagnosis study, airway obstruction in patients
with HF did not influence survival [5]. Yoshihisa et al. [3] found a
significant prognostic impact on the presence of moderate COPD in
HF. According to their study, moderate COPD was associated with
cardiac, non-cardiac, and all-cause mortality in HF.
In severe or very severe COPD, the extent of destructive damage
reaches from airway obstruction to pulmonary vasculature bed.
Pulmonary vasculature damage results in pulmonary vascular
resistance elevation and pulmonary hypertension follows at a late
stage of the disease. These apparent hemodynamic abnormalities
are significant as COPD progresses. Right ventricle is less tolerant
to the elevated afterload than the left ventricle, and right heart
dilatation and hypertrophy occur and systolic and diastolic
dysfunction result [7]. Right ventricular dilatation affects the left
ventricular function by the ventricular septum abnormal motion
and pericardial constraints [8]. Ventricular–ventricular interde-
pendence makes the cardiac function fall in a vicious circle, so that
there is low stroke volume even with elevated filling pressure. This
malignant condition easily leads the HF to be refractory to standard
HF therapy.
However, according to the results of the report from Yoshihisa
et al. [3], the presence of moderate COPD showed similar cardiac
morphology or function with HF patients without COPD. It raises
the question what other pathophysiology other than hemody-
namic alterations leads the patients to adverse outcomes?
According to their results, systemic inflammation, myocardial
injury, and arterial stiffening should play key roles in patho-
physiology in moderate COPD (Fig. 1). Inflammation is an
established marker of cardiovascular risk in Framingham
subjects [9]. Systemic vascular involvement in COPD patients
as cardiovascular risk increases has already been reported by
other investigators [6].
[(Fig._1)TD$IG] Editorial / Journal of Cardiology 64 (2014) 250–252
Fig. 1. Pathophysiological relation between COPD and heart failure. COPD, chronic obstructive pulmonary disease; RAS, renin–angiotensin system.
Skeletal muscle atrophy is pathogenetically important in both
COPD and HF [10]. Systemic inflammation is responsible for the
skeletal muscle alternation.
There have been few prospective studies into combined
treatment of COPD and HF. Therefore, in COPD patients, HF should
be treated according to usual HF guidelines as there is no evidence
that HF should be treated differently in the presence of this
respiratory disease. Statins and renin–angiotensin system (RAS)
blockers may reduce the morbidity and mortality of COPD patients.
Statins and RAS inhibitors may affect the baseline inflammation [6].
The effects of beta-blockers should be clarified according to the
severity of airway limitation in stable patients who have HF and
coexisting COPD. Beta2-blockade in severe airway obstruction
should be avoided due to bronchial spasm in acute decompensated
phase. Importantly, Yoshihisa et al. [3] clearly demonstrated the
beneficial effect of beta-blockers in mild and moderate COPD for
chronic management of HF on 3-year all-cause mortality. The
results suggest the encouraging use of beta-blockers as standard
therapy regardless of the presence of moderate comorbid COPD.
However, the prescription rate of beta-blockers was as low as 58%
in moderate COPD compared to non-COPD of 79% in this
observational study. Therapy with beta-blockers may be withheld
in COPD patients due to concerns of the diminution of the beta2-
agonist bronchodilator effect and the worsening of bronchospasm.
However, there have been several reports supporting the beneficial
effects of beta-blockers in COPD patients with HF, and the selective
beta1-blocker bisoprolol is recommended in the European Society
of Cardiology guidelines [11]. A further prospective trial is needed
in the future. We do not hesitate to start low-dose beta-blocker and
try titrating up in patients with COPD in present clinical practice. In
addition, caution should be advised with the use of inhaled beta2-
agonists for the treatment of COPD in patients with HF at present,
because there have been some reports that inhaled beta-agonist
increases death and hospital admissions [12].
251
The establishment of an appropriate approach to managing
HF accompanied with COPD is needed. In this strategy, we
should try to improve quality of life as well as survival of these
patients.
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