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Review Article
Update in diagnosis and therapy of coexistent chronic obstructive pulmonary disease and chronic heart failure
Department of Respiratory Medicine, the Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
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Abstract
Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) frequently coexist in clinical practice as they share the same risk factors. The manifestations of COPD and CHF are similar. Exertional dyspnoea, easy fatigability and reduced exercise tolerance are common to COPD and CHF and required careful interpretation. Pulmonary function tests, plasma natriuretic peptides, echocardiography and cardiovascular magnetic resonance imaging should be carried out to acquire the objective evidence of pulmonary and cardiac function when necessary. Robust studies indicate that patients with COPD tolerate the cardioselective β-blockers well, so it should not be denied to CHF patients with concomitant COPD. Low-dose initiation and gradual uptitration of cardioselective β-blockers is currently recommended. However, β2-agonists should be used with cautions in COPD patients with CHF, especially in acute exacerbations. Statins, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers may reduce the morbidity and mortality of the patients with COPD.
Key words
Chronic obstructive pulmonary disease; chronic heart failure; beta blockersJ Thorac Dis 2012;4(3):310-315. DOI: 10.3978/j.issn.2072-1439.2012.01.09
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Introduction
Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) are global epidemics, each affecting in excess of 10 million patients. Both conditions incur significant morbidity and mortality, and present significant challenges to healthcare providers (1). Moreover, COPD and CHF also frequently coexist in clinical practice as they share the same risk factors, including cigarette smoking, advanced age and systemic inflammation (2,3).
Prevalence of CHF in patients with COPD
COPD is a frequently concomitant comorbidity in patients with CHF. And it is also an important and independent risk factor for atherosclerosis (4,5). In COPD, CHF is prevalent in more than 20% of patients (6,7). The risk ratio of developing CHF is 4.5 (95% confidence interval 4.25 to 4.95) in COPD patients compared to age-matched controls without COPD after adjustments for cardiovascular risk factors (7,8). The rate adjusted hospital prevalence of CHF is 3 times greater among patients discharged with a diagnosis of COPD compared with patients discharged without mention of COPD (8).
Prevalence of COPD in patients with CHF
In return, in patients with CHF the prevalence of COPD ranges from 20% to 32% (7,9). The reported prevalence of COPD in patients with HF ranges widely from 11 to 52% in North America and from 9 to 41% in European cohorts (1,10). In addition, COPD is more common in male compared with female HF patients and in urban compared with rural areas (1). Moreover, there is a non-linear relationship between age and frequency of concurrent COPD in patients with HF. It is lowest in the young and very elderly, under 55 and over 85 years of age, respectively (10).
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Diagnosis
The prevalence of CHF in patients with COPD and vice versa is well documented. Patients concurrent with COPD and CHF have much worse prognosis in comparison with patients with individual disease (2). COPD patients with concurrent
CHF have twice the risk of dying from a cardiovascular cause
than those without CHF (11). Hence, it is very important to
recognize the concurrent of COPD and CHF.
Symptoms
The clinical manifestations of COPD and CHF are similar
(1-3,8,10). Exertional dyspnoea is the frequent symptom
common to COPD and CHF. Fatigue is also a common, if
nonspecific, complaint of patients with COPD and CHF, which
together with exertional dyspnoea result in marked activity
intolerance. Apart from dyspnoea and fatigue, depression and
anxiety are also common in both COPD and CHF.
However, new onset orthopnoea, nocturnal cough,
paroxysmal nocturnal dyspnoea or acute pulmonary edema,
easy fatigability and reduced exercise tolerance in the absence
of evidence of chest infection in COPD patients should arouse
a suspicion of HF (3). Symptoms of angina tilt the diagnosis
in favor of coronary artery disease with HF. In acute onset
dyspnoea, absence of cough or change in character of sputum
should lead to a search for causes other than acute exacerbations
of COPD, including acute left ventricle failure (3).
Signs
The pulmonary examination and cardiac examination in patients
coexistence of COPD and CHF are usually unremarkable
because of the lung hyperinflation.
Crackles may be heard in COPD due to opening of small
airways. Wheeze is audible in CHF due to airflow limitation in
the smaller airways, while crackles of pulmonary edema may be
inaudible in a hyperinflated chest (3). Presence of jugular venous
distention, ankle edema, and hepatomegaly in COPD should
arouse the suspicion of right ventricular failure (1,3). Presence of
a loud P2 and left parasternal heave point towards cor-pulmonale
while a pansystolic murmur over the mitral area may be due to a
papillary muscle dysfunction in coronary artery disease (3).
In a word, the signs and symptoms of coexistence COPD and
CHF are neither specific nor sensitive. Additional laboratory
testing should be performed in a patient with COPD or CHF.
Chest radiography
Chest radiography is insensitive for detecting the coexistence.
On one hand, the cardiothoracic ratio may remain in the
normal range as the heart tends to become long and narrow in a
hyperinflated chest (3). On the other hand, pulmonary vascular
remodelling and radiolucent lung fields mask the typical alveolar
shadowing of pulmonary oedema (1). But chest radiography
may be useful for detecting additional disease.
Pulmonary function tests (PFTs)
Objective evidence of airflow obstruction is mandatory for
diagnosing COPD. According to the GOLD criteria : a postdilatory
ratio of forced expiratory volume in 1s and forced vital
capacity of less than 0.7 (FEV1/FVC <0.7) measured with
spirometry confirmed the diagnosis of COPD (12). Recently,
ACP, ACCP, ATS and ERS recommend that spirometry should
be obtained to diagnose airflow obstruction in patients with
respiratory symptoms, and spirometry should not be used to
screen for airflow obstruction in individuals without respiratory
symptoms (13).
CHF has a mixed effect on pulmonary function. Patients
coexistence with COPD and CHF have combined obstruction
and restriction in PFTs (14,15). However, Lung function can
improve after treatment of CHF. With diuresis, mean FEV1
improves by up to 35% and returns to normal. So in patients with
CHF, it is advisable to repeat spirometry after patients have been
titrated to recommended doses of CHF medication to make a
final diagnosis of COPD (15).
Plasma B-type Natriuretic Peptides (BNP)
Plasma B-type Natriuretic Peptides is a rapid and sensitive
biomarker for diagnosing CHF from patients with COPD (16).
A single cut point for BNP to exclude/detect CHF is </≥100
pg/mL. CHF is unlikely when BNP levers are <100 pg/ml. In
COPD patients, BNP levels ranging from 100 to 500 pg/ml
indicate right-sided (R) heart failure, moderate left-sided heart
failure, or both and the need to initiate therapy with angiotensinconverting
enzyme (ACE) inhibitors and possibly loop diuretics.
Although not specifically tested in patients with a history of
COPD, BNP >500 pg/ml is suggested by others to indicate acute
HF in COPD and CHF therapy should be intiated (3,5,8,17).
When BNP added to clinical judgment, 95-100% of the patients
are correctly diagnosed (3,17). For NT-proBNP, a value of <300
pg/ml to exclude HF, and of >450 pg/ml for patients <50 years
and of >900 pg/ml for those ≥50 years to detect HF is tested in
patients with previous COPD presenting with acute dyspnoea
(17). However, the recent NICE guidelines recommend that a
BNP level > 400 pg/ml or an NT-proBNP level > 2000 pg/ml
should arouse the suspicion of HF (18).
Echocardiography
Echocardiography is a valuable tool to study the structure and the
function of the heart noninvasively and safely. The NICE guidelines
recently recommend that the echocardiogram and the specialist
clinical opinion should be referred within 2 weeks if BNP >400
pg/ml or NT-proBNP >2000 pg/ml, or within 6 weeks if BNP
100-400 pg/ml or NT-proBNP 400-2000 pg/ml (18). A normal echocardiogram excludes CHF. No CHF therapy is needed.
The diagnosis of diastolic heart failure needs to be considered in
COPD patients with LV ejection fraction >40% and abnormal
LV mass or enlarged left atrium by echocardiography or impaired
LV filling by radionuclide ventriculography (RNV), and the
response to ACE inhibitors and loop diuretics needs to be closely
monitored. When patients with COPD have an LV ejection
fraction ≤40%, full CHF therapy including beta-adrenergic
blockade is recommended (8).
Cardiovascular Magnetic Resonance Imaging (CMR)
Cardiovascular magnetic resonance imaging (CMR) is the
accepted reference standard for measuring LV volumes and
ejection fraction (1). It offers a powerful tool to detect or
exclude CHF in stable patients with mild to moderate COPD.
Combination of CMR measurements of left ventricular ejection
fraction, indexed left and right atrial volume, and left ventricular
end-systolic dimensions provide high added diagnostic value
beyond clinical items (ROC-area 0.91) for identifying CHF.
Right ventricular mass divided by right ventricular enddiastolic
is higher in COPD patients with CHF than in those
without concomitant CHF. Disadvantages of CMR include
the acquisition time, limited availability, and a higher price
than echocardiography (19). Professional imaging societies
recommend CMR to evaluate LV function in HF patients with
technically limited echocardiogram images (1).
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Therapy
Oxygen Therapy
Oxygen therapy is one of the principal nonpharmacologic
treatments that improve survival in COPD. Recently, Global
initiative for chronic obstructive lung disease (GOLD)
recommends to introduce long-term oxygen therapy (LTOT) in
patients with Stage IV: Very Severe COPD who have: PaO2 is at
or below 7.3 kPa (55 mm Hg) or SaO2 is at or below 88%, with
or without hypercapnia; or PaO2 between 7.3 kPa (55 mm Hg)
and 8.0 kPa (60 mm Hg), or SaO2 of 88%, if there is evidence
of pulmonary hypertension, peripheral edema suggesting
congestive cardiac failure, or polycythemia (hematocrit >55%)
(20). Currently, no evidence exists that long-term oxygen
therapy reduces breathlessness or the frequency of clinical
events (such as admission to hospital or mortality) in patients
with CHF (21). But we still should prescribe oxygen therapy in
patients hospitalized with severe CHF and COPD exacerbation
as it may improve oxygenation. Patients with COPD and CHF
may often experience isolated nocturnal hypoxaemia, more
studies are needed to evaluate whether nocturnal oxygen therapy
may be of benefit to these patients.
Antibiotics
Infection is the most common causes of an exacerbation of
COPD and CHF. In COPD patients with or without CHF,
the presence of fever, purulent sputum, leukocytosis and a
new or changing radiographic infiltrate is sufficient indication
for starting empirical antibiotic treatment. If an infectious
exacerbation does not respond to the initial antibiotic treatment,
a sputum culture and a drug susceptibility test should be
performed. Once the etiologic agent is known, treatment
should be altered to target the specific pathogen. A diagnosis of
pulmonary embolism should be considered in patients who do
not respond to appropriate antimicrobial treatment.
β-blockers
Despite clear evidence of the effectiveness of β-blockers
in the management of patients with CHF, the use of these
agents has traditionally been contraindicated in COPD,
mainly because they might cause acute bronchospasm,
increase airway hyperresponsiveness and worsen respiratory
symptoms. Recently, the NICE and European Society of
Cardiology (ESC) guidelines clearly state that COPD is not a
contraindication to the use of β-blockers, and mild deterioration
in pulmonary function and symptoms should not lead to prompt
discontinuation. Low-dose initiation and gradual uptitration is
recommended (18,22).
β-blockers can be divided into two kinds, cardioselective
β-blockers and nonc ardiosel ective β-blockers. The
cardioselective β-blockers have greater selective affinity for β1- than β2- receptors, whereas the noncardioselective β-blockers
have similar affinity for both β1- and β2- receptors as well
as α-blocking capacity. However, cardioselectivity is dosedependent.
Higher plasma concentrations increase competitive antagonism of β2-receptors with only limited incremental β1- blockade (23).
Effect of β-blockers on lung function
There is increasing evidence suggesting that respiratory
symptoms and FEV1 are not significantly worsened by
cardioselective β-blockers in COPD. In a recent meta-analysis
of the relation between cardionselective β-blockers and COPD,
no significant differences were noted in FEV1 or respiratory
symptoms between patients treated with a cardioselective
β-blocker and those treated with a placebo, even in patients with
severe COPD (24).
Carvedilol is the only noncardioselective β-blocker approved
for treating CHF, and tolerated by the patients coexistent with
CHF and COPD. In a randomized, open label, triple-crossover
trial examed 35 patients with coexistent COPD according to GOLD criteria, FEV1 was significantly lower with carvedilol
(1.85 l/s) than with metoprolol (1.94 l/s) and bisoprolol (2.00 l/s).
But it suggested that switching from β1-blockers to carvedilol was
safe (9). Hence, more studies are needed to ascertain the effect
of noncardioselective β-blocker on COPD.
Effect of β-blockers on mortality and risk of exacerbation in COPD
Use of cardioselective β-blockers is consistently associated with
better survival in patients with CHF and concurrent COPD in
observational studies (25,26). In the Val HeFT (Valsartan Heart
Failure Trial), 140 (22%) of 628 participants with physicianrecorded
COPD received β-blockers. Mortality over a mean of
23 months was approximately 17%, as opposed to 31% in those
with HF and COPD not prescribed β-blockers (P<0.001) (25).
Dransfield and co-workers assessed 825 inpatients admitted
for acute exacerbations of COPD, and noted that the use of
β-blockers was associated with a reduced rate of mortality
in hospital (OR=0.39; 95% CI 0.14 to 0.99). The benefit of
β-blockers was observed despite patients who were treated
being older, having longer hospital stays, and having a greater
prevalence of congestive heart failure and cerebrovascular
disease, all factors that were independent predictors of inhospital
mortality (26).
Moreover, a recent observational cohort study showed
that long-term treatment with β-blockers might improve
survival and reduce the risk of an exacerbation of COPD in
the broad spectrum of patients with a diagnosis of COPD,
including those who have COPD with but, importantly,
also without overt cardiovascular comorbidities (27). Short
and colleagues investigated the effect of β-blockers added to
specific treatment regiments for COPD across the spectrum
of disease severity. They assessed 5977 patients aged >50 years
with a diagnosis of COPD and noted that β blockers may
reduce mortality and COPD exacerbations when added to
established inhaled stepwise therapy for COPD, independently
of overt cardiovascular disease and cardiac drugs, and without
adverse effects on pulmonary function (28). However, we need
prospective studies to ascertain any beneficial effect of β-blockers
on COPD related outcomes.
In summary, COPD (even moderate or severe) is not a
contraindication to β-blockers (23,29). It is recommended to
only use those β-blockers that are more selective for the β1-AR at
the lowest dose and to titrate them slowly with attention to lung
function and symptoms, adding an inhaled antimuscarinic agent
when bronchodilation is needed (29).
Bronchodilators in patients with CHF
Inhaled β2-agonists induce adverse cardiac effects in COPD patients with pre-existing cardiovascular disease. In particular,
the adverse effects of β2-agonists are likely to be exacerbated
in COPD patients with coexistent CHF (29). Hawkins et
al. assessed 7599 patients with symptomatic HF to receive
candesartan or placebo. Bronchodilator use was associated
with increased all-cause mortality, cardiovascular death, HF
hospitalization, and major adverse cardiovascular events. The
adverse outcomes were consistent in patients with reduced and
preserved systolic function. But no significant interaction was
observed between bronchodilators and beta-blockade with
respect to outcomes (30). However, a recent rat model of dilated
cardiomyopaty indicated that a combination of β2-AR agonists
and a β1-AR blocker is more effective than β1-AR blocker alone
and as effective as β1-AR blocker with ACE inhibitor with respect
to treatment of dilated cardiomyopathy. This combined regimen
of β2-AR agonists and a β1-AR blocker might be considered for
clinical testing as alternative or adjunct therapy to currently
acceptable CHF arsenal (31).
Currently, clinicians should only prescribe β2-agonists for
clear symptom relief, after carefully considering the etiology of
dyspnoea and objectively documenting airflow obstruction. Oral
β2-agonists should be avoided, and both the dose and frequency
of nebulized therapy should be minimized (23).
Statins and ACE inhibitors
Observational studies suggest that statins, angiotensin-convertingenzyme
(ACE) inhibitors, and angiotensin-receptor blockers
(ARBs) can reduce the morbidity and mortality of the patients
with COPD (32,33). A time-matched nested case-control study
showed that statins, ACE inhibitors, and ARBs may have dual
cardiopulmonary protective properties, thereby substantially
altering prognosis of patents with COPD. The combination
of statins and ACE inhibitors or ARBs was associated with a
reduction in COPD hospitalization and total mortality rates in
cohorts with high and low cardiovascular risks. Furthermore,
this drug combination reduced myocardial infarction rate in the
COPD cohort with high cardiovascular risk, independently of
the concomitant use of steroids (32). Mortensen et al. reported
that the use of statins and ACE inhibitors prior to admission was
associated with decreased mortality in subjects hospitalized with a
COPD exacerbation (33).
Moreover, a recent prospective study followed up 245 patients
admitted to hospital for exacerbations of COPD (ECOPD) for
one year. It showed that there was no effect of statins on either
30-days or 1-year mortality. Patients receiving statins presented
a lower total number of ECOPD during the 1-year follow up.
After proper adjustments, the use of statins was associated with
a lower risk for ECOPD and severe COPD. The group of statins
presented better improvement in health-related quality of life at 2,
6 and 12 months (34).
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Conclusions
COPD and CHF frequently coexist in clinical practice,
and importantly influence each other in both management
and prognosis. Clinical symptoms and signs require careful
interpretation. Objective evidence of each condition should be
obtained. The cardioselective β-blockers should not be denied
to the patients who have coexistent COPD and CHF. Low-dose
initiation and gradual uptitration of cardioselective β-blockers is
currently recommended. However, β2-agonists should be used
with cautions, especially in acute exacerbations. Statins, ACE
inhibitors, and ARBs may reduce the morbidity and mortality of
the patients with COPD.
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References
Cite this article as: Zeng Q, Jiang S. Update in diagnosis and therapy of
coexistent chronic obstructive pulmonary disease and chronic heart failure. J
Thorac Dis 2012;4(3):310-315. doi: 10.3978/j.issn.2072-1439.2012.01.09
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