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REVIEW
Heart failure and chronic obstructive pulmonary
disease: diagnostic pitfalls and epidemiology
Nathaniel Mark Hawkins1*, Mark C. Petrie2, Pardeep S. Jhund3,
George W. Chalmers2, Francis G. Dunn4, and John J.V. McMurray3
1
Aintree Cardiac Centre, University Hospital Aintree, Longmoor Lane, Liverpool L9 7AL, UK;
2
Royal Infirmary, Glasgow, UK;
3
Western Infirmary, Glasgow, UK; and
4
Stobhill
Hospital, Glasgow, UK
Received 24 January 2008; revised 31 August 2008; accepted 3 November 2008
Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are global epidemics incurring significant morbidity and mortality. The com-
bination presents many diagnostic challenges. Clinical symptoms and signs frequently overlap. Evaluation of cardiac and pulmonary function is often
problematic and occasionally misleading. Echocardiographyand pulmonary function tests should be performed in every patient. Careful interpret-
ation is required to avoid misdiagnosis and inappropriate treatment. Airflow obstruction, in particular, must be demonstrated when clinically euvo-
laemic. Very high and verylow concentrations of natriuretic peptides have high positiveand negative predictive values for diagnosing HF in those with
both conditions. Intermediate valuesare less informative. Both conditions are systemic disorderswith overlapping pathophysiological processes. In
patients with HF, COPD is consistently an independent predictor of death and hospitalization. However, the impact on ischaemic and arrhythmic
events is unknown. Greater collaboration is required between cardiologists and pulmonologists to better identify and manage concurrent HF and
COPD. The resulting symptomatic and prognostic benefits outweigh those attainable by treating either condition alone.
-----------------------------------------------------------------------------------------------------------------------------------------------------------
Keywords Heart failure †Chronic obstructive pulmonary disease
Introduction
Heart failure (HF) and chronic obstructive pulmonary disease are
global epidemics, each affecting in excess of 10 million patients.
1,2
Both conditions incur significant morbidity and mortality, and
present major challenges to healthcare providers.
1
Few reports have
addressed this often ignored combination, and fewer still the simple
questions of interest to physicians. What are the pitfalls of diagnosing
HF in patients with chronic obstructive pulmonary disease, and vice
versa? How frequent a comorbidity is chronic obstructive pulmonary
disease? What are the clinical consequences of both conditions
co-existing? Here, we examine the diagnostic problems posed by the
two conditions, before reviewing the prevalence and prognostic impli-
cations of chronic obstructive pulmonary disease in patients with HF.
Problems diagnosing heart failure
in patients with chronic
obstructive pulmonary disease
Clinical features
Heart failure is a complex syndrome without a simple objective
definition. Diagnosis requires both typical clinical features and
objective evidence of cardiac dysfunction.
2
Pulmonary disease
may produce or obscure every symptom and sign defined by Fra-
mingham criteria.
3
Exertional breathlessness, nocturnal cough, and
paroxysmal nocturnal dyspnoea are common to both conditions.
No qualitative features of dyspnoea are unique to HF.
4
Stigmata
of right ventricular failure may also be misleading, including
jugular venous distention, ankle oedema, and hepatomegaly. Lung
hyperinflation with hepatic displacement mimics the latter, while
hindering palpation of cardiomegaly and auscultation of rales or a
third heart sound. The difficulty in differentiating between HF
and chronic obstructive pulmonary disease symptoms and signs
is illustrated in a single cohort study comparing the Framingham
and Cardiovascular Health Study criteria for HF. The prevalence
of concurrent chronic obstructive pulmonary disease was twice
as great in patients fulfilling only Framingham as opposed to only
Cardiovascular Health Study criteria (13% vs. 6%).
5
Radiology
Radiological evidence of HF is likewise influenced by the presence of
chronic obstructive pulmonary disease.
6,7
Chest hyperinflation spur-
iously reduces the cardiothoracic ratio. Pulmonary vascular remodel-
ling and radiolucent lung fields mask the typical alveolar shadowing of
pulmonary oedema.
7,8
Asymmetric, regional, and reticular patterns of
*Corresponding author. Tel: þ44 151 529 2717, Fax: þ44 151 529 2724, Email: nathawkins@hotmail.com
Published on behalf of the European Society of Cardiology. All rights reserved. &The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.
European Journal of Heart Failure (2009) 11, 130–139
doi:10.1093/eurjhf/hfn013
pulmonary oedema are commonplace in those with concurrent
chronic obstructive pulmonary disease.
6,7,9
Emphysematous vascular
bed loss causes upper lobe venous diversion, mimicking HF.
9
Isolated
right HF is also said to cause pleural effusions through impaired
pleural lymphatic drainage secondary to elevated systemic venous
pressure.
10
However, in clinical practice pleural effusions are rarely
due to right HF alone.
11,12
Echocardiography
Transthoracic echocardiography may be impeded by poor acoustic
windows caused by the pathological changes associated with
chronic obstructive pulmonary disease.
13
Inadequate visualization
may relate to air trapping. In a recent primary care study, echocar-
diographic images were unsatisfactory in 10.4% of patients with
chronic obstructive pulmonary disease.
14
This proportion
increases to 35% in patients with severe chronic obstructive pul-
monary disease,
15
and 50% in those with very severe airflow
obstruction.
16
Although studies have assessed contrast echocar-
diography in patients with poor endocardial definition, those
with pulmonary disease were often excluded.
17,18
In lung trans-
plant candidates, Doppler estimation of pulmonary artery pressure
was less frequently possible in patients with a residual volume
exceeding 150% predicted (40% vs. 56%, P¼0.007).
19
Studies
would be welcome comparing the accuracy of left ventricular ejec-
tion fraction (LVEF) measured by contrast echocardiography
against cardiac magnetic resonance imaging (CMR) in patients
with chronic obstructive pulmonary disease.
Cardiac magnetic resonance imaging
Cardiac magnetic resonance imaging is the accepted reference
standard for measuring LV volumes and ejection fraction.
20
Results are accurate, reproducible, and extensively validated.
20,21
The CMR allows precise quantification of RV volumes, function,
and transvalvular flow, while avoiding ionizing radiation.
22
Tissue
characterization additionally identifies myocardial fibrosis that
may predict risk of arrhythmias.
23
Professional imaging societies
recommend CMR to evaluate LV function in HF patients with
technically limited echocardiogram images.
24
Natriuretic peptides
Both B-type natriuretic peptide (BNP) and N-terminal pro-BNP are
useful for excluding HF in subjects with acute dyspnoea.
25– 27
The
diagnostic accuracy of BNP in patients with concurrent chronic
obstructive pulmonary disease is less certain. Subgroup analysis of
417 patients with chronic obstructive pulmonary disease or asthma
in the Breathing Not Properly study reported a mean BNP for
those with and without HF of 587 +426 and 109 +221 pg/mL,
respectively (P,0.0001).
28
In a Californian study of 321 patients
presenting with acute dyspnoea, mean BNP was significantly higher
in patients with HF compared with those with chronic obstructive
pulmonary disease (75 9 +798 vs. 54 +71 pg/mL, P,0.001).
29
Both studies have two major limitations. First, the diagnosis of HF
was adjudicated retrospectively by two cardiologists based on clinical
criteria and subsequent investigations; in the Breathing Not Properly
subgroup only 29% of patients had echocardiography.
28
Secondly,
right HF from cor pulmonale was possibly misdiagnosed or even
specifically classified as HF.
29
This falsely magnifies the apparent
accuracy of BNP while neglecting the question of interest to clini-
cians, for whom diagnosing HF due to left ventricular dysfunction is
paramount in guiding future therapy.
Plasma BNP is elevated in both primary pulmonary hypertension
and right HF secondary to chronic respiratory disease.
31,32
Levels of
BNP correlate with pulmonary artery pressure and independently
predict mortality.
31,32
However, few studies have assessed BNP
specifically in patients with chronic obstructive pulmonary
disease.
32,34
Only one has examined the ability to identify HF in
these patients.
35
Four natriuretic peptide assaysproduced comparable
results in 200 stable elderly patients with a clinical diagnosis of chronic
obstructive pulmonary disease. Each test excluded HF with reasonable
accuracy (all negative predictive values above 0.85). However, the
positive predictive value and overall diagnostic accuracy were lower
than observed in patients with acute dyspnoea.
26,27
The explanation
is two-fold. Stable patients exhibit lower BNP levels than those with
acute volume overload and raised intracardiac pressures. Secondly,
BNP levels are increasedin patients with chronic obstructive pulmon-
ary disease.
32,35
Both factors lessen the diagnostic accuracy in these
patients. The BNP Consensus Panel guidelines state that cor pulmo-
nale is associated with an intermediate elevation of BNP, typically
ranging from 100 to 500 pg/mL.
25
Levels ,100 and .500 pg/mL
have high negative and positive predictive values, respectively, for
HF. Between these thresholds a Bayesian approach is warranted,
using BNP to corroborate the clinical evaluation.
Problems diagnosing heart failure
with preserved ejection fraction in
patients with chronic obstructive
pulmonary disease
Defining and identifying HF with preserved ejection fraction (HF-PEF)
is controversial and problematic in any population. These difficulties
are magnified in patients with chronic obstructive pulmonary disease.
BNP levels are moderately elevated in both HF-PEF and cor
pulmonale.
36– 38
One small study compared 17 patients with
chronic obstructive pulmonary disease against 9 patients with
HF-PEF, defined by clinical and radiological pulmonary oedema
responding to treatment, sinus rhythm, and preserved LV ejection
fraction. BNP levels were significantly higher in those with HF-PEF
(224 vs. 14 pg/mL, P,0.0001).
34
However, BNP was ,100 pg/ml
in four of the nine patients with HF-PEF, while few patients with
chronic obstructive pulmonary disease had significant pulmonary
hypertension (mean systolic pulmonary artery pressure was
36 mmHg). More robust studies are required to determine the diag-
nostic accuracy of BNP for HF in patients with chronic obstructive
pulmonary disease and varying levels of pulmonary hypertension.
Problems diagnosing chronic
obstructive pulmonary disease
in patients with heart failure
Patients with HF exhibit both obstructive and restrictive venti-
latory defects, which may compound or conceal the characteristic
Heart failure and chronic obstructive pulmonary disease 131
airflow limitation of chronic obstructive pulmonary disease. Spiro-
metry defines three standard indices: forced expiratory volume in
1 s (FEV
1
); forced vital capacity (FVC), the total volume delivered
during forced expiration from a maximum inspiration; FEV
1
/FVC
ratio, the proportion of the total volume expired in the first
second.
39
Obstruction is defined by a reduced FEV
1
/FVC ratio of
,70% in the Global Initiative for Chronic Obstructive Lung
Disease (GOLD) and American Thoracic Society/European Respir-
atory Society guidelines.
1,40
Restriction is characterized by reduced
lung volumes. Both FEV
1
and FVC are decreased with a normal or
raised FEV
1
/FVC ratio. Since this pattern also occurs in severe
obstruction with air trapping, the diagnosis of restriction addition-
ally requires detection of reduced total lung capacity by
plethysmography.
39
Obstructive pulmonary function tests
Airflow obstruction is common in patients with decompensated
HF,
41,42
contrasting with restrictive defects when HF is stable.
Interstitial and alveolar oedema cause compression and obstruc-
tion of the airways, compounded by bronchial hyperresponsive-
ness.
43,44
Both misdiagnosis and overestimation of chronic
obstructive pulmonary disease severity may result. With diuresis,
mean FEV
1
improves by up to 35% and often returns to
normal.
41,42
Pulmonary function tests are therefore most informa-
tive when patients are clinically euvolaemic.
A mild obstructive ventilatory pattern may be observed even
when not fluid overloaded. A comparison dichotomising patients
around a peak oxygen consumption of 14 mL/min/kg noted a
lower FEV
1
/FVC ratio in severe HF (70% vs. 75%, P¼0.008).
45
The ratio also declines with age in the general population, reaching
70% in those over 75 years of age.
46
Chronic obstructive
pulmonary disease may thus be over diagnosed in elderly patients
with HF.
47
Restrictive pulmonary function tests
Restrictive ventilatory defects predominate in patients with stable
HF.
48
FEV
1
and FVC were normal or proportionately reduced in
a multicentre study of 130 patients.
49
Contributory factors
include interstitial fibrosis,
50
respiratory muscle weakness,
45,51,52
cardiomegaly, and pulmonary congestion.
53
FEV
1
and FVC may
also be proportionately reduced with a normal ratio in patients
with severe chronic obstructive pulmonary disease and gas trap-
ping. Usually in such cases increased total lung capacity and residual
volume help diagnose obstruction.
39
However, restricted lung
volumes mask hyperinflation and thus the diagnosis of chronic
obstructive pulmonary disease in patients with concurrent HF.
6
Performing spirometry
Objective evidence of airflow obstruction is mandatory for diag-
nosing chronic obstructive pulmonary disease.
1
Approximately
one-third of patients labelled with chronic obstructive pulmonary
disease do not fulfil the GOLD criteria (Table 1).
35,54
Despite
this, many physicians fail to confirm or refute the clinical diagnosis
using spirometry. A recent US study revealed significant disparities
in confirmatory testing practices.
54
Among 219 patients discharged
from a tertiary centre with both HF and chronic obstructive pul-
monary disease, 82% received echocardiography as opposed to
36% pulmonary function testing. This lack of adherence to guide-
lines must be addressed, as both inhaled therapy and beta-
blockade are dictated by the degree of airflow obstruction.
Prevalence of chronic obstructive
pulmonary disease in patients with
heart failure
Estimates of chronic obstructive pulmonary disease prevalence
vary according to the population studied, diagnostic criteria
applied, measurement tools, and surveillance systems.
55
Geo-
graphical variations largely relate to differences in population age
structure and risk factor exposure, most notably smoking.
1,55
The prevalence of chronic obstructive pulmonary disease was
greater in patients with HF than the general population in the Car-
diovascular Health Study (20% vs. 13%, P¼0.001).
56
This may
reflect both clustering of aetiological factors and misdiagnosis.
No study has systematically examined pulmonary function in
patients with stable HF.
57
How many have severe, reversible, or
misdiagnosed airflow obstruction is unknown.
The reported prevalence of chronic obstructive pulmonary
disease ranges from 11 to 52% in North American patients with
HF, and from 9 to 41% in European cohorts (Table 2). Half of the
studies originate in the USA. The prevalence of chronic obstructive
pulmonary disease is greater in more recent studies (Table 2). Four
studies examining trends in HF epidemiology confirm the increasing
prevalence.
58 – 61
This may represent greater awareness of chronic
obstructive pulmonary disease, an ageing population or increasing
age at onset of HF. A consistent non-linear relationship is apparent
between age and frequency of concurrent chronic obstructive pul-
monary disease in patients with HF.
62 – 65
The prevalence increases
until around 75 years of age, and declines thereafter. Possibly the
presence of chronic obstructive pulmonary disease reduces survival
beyond this age. Alternatively, less intensive investigations in the
elderly may under-diagnose comorbidity.
Chronic obstructive pulmonary disease is more common in male
compared with female HF patients,
65–70
and in urban compared with
rural areas.
71
The prevalence is notably lower (by 6–11%) in those
managed by cardiologists as opposed to general physicians.
72– 75
................................................................................
Table 1 GOLD classification of chronic obstructive
pulmonary disease severity based on
post-bronchodilator FEV
1
Stage FEV
1
/FVC FEV
1
predicted
I: mild ,0.70 FEV
1
80%
II: moderate ,0.70 50% FEV
1
,80%
III: severe ,0.70 30% FEV
1
,50%
IV: very severe ,0.70 FEV
1
,30% or FEV
1
,50% plus
chronic respiratory failure
FEV
1
, forced expiratory volume in one second; FVC, forced vital capacity;
respiratory failure, arterial partial pressure of oxygen (PaO
2
),8.0 kPa (60 mmHg)
with or without arterial partial pressure of CO
2
(PaCO
2
).6.7 kPa (50 mmHg)
while breathing air at sea level.
N.M. Hawkins et al.132
...............................................................................................................................................................................
Table 2 Prevalence of chronic obstructive pulmonary disease in patients with heart failure
Reference Prevalence (%) Country Data collection nPopulation Data source
Rich
119
11 USA 1983–1986 410 HF hospitalization Washington University Hospital
Bangdiwala
120
15 USA and Canada 1988–1989 6273 HF hospitalization SOLVD Registry
Auerbach
73
19 USA 1989–1994 1298 HF hospitalization SUPPORT Study
Barker
58
18 USA 1990–1994 393 HF hospitalization Kaiser Permanente Centre Health
Research
Wang
121
12 USA 1989–1995 231 HF hospitalization Philadelphia Geriatric Centre
Mathew
122
19 USA 1992–1995 301 Mixed Cook County Hospital
Harjai
112
18 USA 1994–1995 434 HF hospitalization Ochsner Foundation Hospital
Kitzman
56
20 USA 1994–1995 425 Outpatient Cardiovascular Health Study
Vaccarino
68
27 USA 1994–1995 2445 HF hospitalization Connecticut Peer Review
Organization
Gambassi
63
19 USA 1992–1996 86 094 Outpatient SAGE Database
Polanczyk
61
24 USA 1994–1996 1896 HF hospitalization Massachusetts General Hospital
Baker
60
25 USA 1991–1997 23 505 HF hospitalization Cleveland Health Quality Choice
Program
Ansari
72
26 USA 1996–1997 403 Outpatient Kaiser Permanente Medical Care
Program
Braunstein
114
26 USA 1999 122 630 Outpatient Medicare
Kosiborod
59
33 USA 1992–1999 3 957 520 HF hospitalization Medicare
Havranek
64
33 USA 1998–1999 34 587 HF hospitalization National Heart Failure Project
Rathore
123
33 USA 1998–1999 30 996 HF hospitalization National Heart Failure Project
Kamalesh
124
52 USA 1999–2000 495 Outpatient Indianapolis Veterans Affairs
Medical Centre
Goldberg
125
34 USA 2000 2445 HF hospitalization Worcester Metropolitan Hospitals
Laramee
126
22 USA 1999–2001 287 HF hospitalization Fletcher Allen Medical Centre,
Vermont
Rector
127
24 USA 1999–2003 769 HF hospitalization Minneapolis Veterans Affairs
Medical Centre
Ezekowitz
128
32 Canada 1993– 2001 12 065 HF hospitalization Alberta Health Care Insurance
Registry
Lee
129
21 Canada 1999– 2001 2624 HF hospitalization EFFECT Study
Nieminen
108
19 Europe 2004 – 2005 3580 HF hospitalization EuroHeart Failure Survey II
Brown
110
12 Scotland 1995 27 477 HF hospitalization Scottish Morbidity Record
Murphy
130
15 Scotland 1999–2000 973 Community Primary Care Records
Newton
131
9 England 1998–2001 528 HF hospitalization Leicestershire Health Authority
Van Jaarsveld
132
9 Netherlands 1993–1998 293 Community Groningen Longitudinal Aging Study
Bouvy
133
19 Netherlands - 152 Mixed Trial of Pharmacist Intervention
van der Wel
65
25 Netherlands 1999–2003 269 Community Nijmegen Practice-Based Research
Network
Taubert
71
11 Germany 1997–1998 266 HF hospitalization Ludwigshafen Heart Failure Registry
Jost
134
20 Germany 1995–2004 675 Mixed Ludwigshafen Heart Failure Registry
Martinez-Selles
69
30 Spain 1996 1065 HF hospitalization Heart failure Observation of Local
Admissions
Di Lenarda
90
41 Italy 2000 2127 HF hospitalization TEMISTOCLE Study
Senni
135
17 Italy 2003 807 Mixed Italian College of General
Practitioners
Macchia
70
24 Italy 2003 1020 HF hospitalization Northern Italian Local Health
Authorities
Tavazzi
136
30 Italy 2004 2807 HF hospitalization Italian survey on Acute Heart
Failure
Siirila-Waris
137
13 Finland 2004 620 HF hospitalization Finnish Acute Heart Failure Study
Gustafsson
66
22 Denmark 1993 – 1996 5491 HF hospitalization DIAMOND-CHF Registry
Galatius
138
8 Denmark 1999 – 2001 283 Community Frederiksberg University Hospital
Continued
Heart failure and chronic obstructive pulmonary disease 133
Non-cardiac comorbidity is a well recognized barrier to specialty refer-
ral.
76
Alternatively, cardiologists perhaps fail to recognize airways
disease. In patients with preserved ejection fraction the reported preva-
lence is generally higher (Table 3).
77–87
A degree of misdiagnosis
undoubtedly exists.
88
Finally, remarkably few clinical trials report the
presence of chronic obstructive pulmonary disease (Table 4). In
these, the lower prevalence of 7– 13% in stable outpatients suggests
significant recruitment bias.
Measurement of ejection fraction inherently changes the esti-
mated prevalence. In the Olmsted County study,
89
23% of patients
...............................................................................................................................................................................
Table 2 Continued
Reference Prevalence (%) Country Data collection nPopulation Data source
Rohde
139
21 Brazil 2000–2004 779 HF hospitalization Hospital de Clinicas de Porto
Alegre
Wright
111
19 New Zealand 1996–1997 197 HF hospitalization Auckland Heart Failure
Management Program
Chong
140
12 Malaysia — 97 HF hospitalization Kuala Lumpur General Hospital
HF, heart failure.
...............................................................................................................................................................................
Table 3 Prevalence of chronic obstructive pulmonary disease in patients with HF and reduced or preserved left
ventricular ejection fraction
Reference Ejection
fraction
Prevalence chronic
obstructive pulmonary
disease (%)
P-value
(preserved
vs. reduced)
nPopulation Country
Masoudi
77
Preserved 34 P,0.001 6754 HF hospitalization USA
Reduced 31 12 956
Ansari.
78
Preserved 30 P¼0.075 147 Community USA
Reduced 21 191
Dauterman
79
Preserved 33 P¼0.32 430 HF hospitalization USA
Reduced 29 352
Gustafsson
80
Preserved 26 P,0.001 2218 HF hospitalization Denmark
Reduced 19 3022
Bursi
81
Preserved 38 P¼0.06 308 Community USA
Reduced 30 248
Bhatia
82
Preserved 18 P¼0.002 880 HF hospitalization Canada
Reduced 13 1570
McDermott
83
Preserved 21 P¼0.80 92 HF hospitalization USA
Reduced 19 206
Liao
84
Preserved 21 P¼0.02 186 Community USA
Reduced 11 166
Ilksoy.
85
Preserved 41 P¼0.72 26 HF hospitalization USA
Reduced 36 63
Kjaergaard
86
Preserved 27 P¼0.15 96 HF hospitalization Denmark
Reduced 20 276
Agoston
87
Preserved 38 — 121 HF hospitalization USA
Reduced 28 327
Ahmed
141
Preserved 24 P¼1 238 HF hospitalization USA
Reduced 24 200
Tribouilloy
142
Preserved 20 P¼0.91 368 HF hospitalization France
Reduced 21 294
Diller
143
Preserved 44 P¼NS 54 Community USA
Reduced 48 82
Berry
144
Preserved 7 P¼0.16 130 HF hospitalization Scotland
Reduced 11 315
Varadarajan
145
(VA
Hospital)
Preserved 4 P,0.0001 963 HF hospitalization USA
Reduced 9 1295
HF, heart failure.
N.M. Hawkins et al.134
with HF had ‘restrictive/chronic obstructive pulmonary disease’.
However, the prevalence was lower (15%) among those under-
going echocardiographic assessment. An incorrect diagnosis of
chronic obstructive pulmonary disease may be removed once
left ventricular systolic dysfunction (LVSD) is confirmed. Addition-
ally, fewer patients with chronic obstructive pulmonary disease are
referred for echocardiography. Across 417 Italian centres, chronic
obstructive pulmonary disease independently predicted failure to
assess LV function during hospitalization (OR 1.25; 95% CI 1.02–
1.53).
90
Prevalence of heart failure in
patients with chronic obstructive
pulmonary disease
Cigarette smoking, the commonest cause of chronic obstructive
pulmonary disease, is associated with a 50% increased risk of
HF.
80,91,92
Two studies have diagnosed HF using standardized cri-
teria in patients with chronic obstructive pulmonary disease.
28,93
Both examined the prevalence of unrecognized HF, excluding
patients with an existing diagnosis. The prevalence of HF was
20.9% in a highly selected cohort with chronic obstructive pulmon-
ary disease or asthma presenting to the emergency department with
acute dyspnoea.
28
However, the diagnosis was adjudicated retro-
spectively by two cardiologists, with echocardiography performed
in only 29% of participants. The prevalence of unrecognized HF
was the same (20.5%) in a comprehensive community study of
405 elderly patients with stable chronic obstructive pulmonary
disease.
93
Heart failure was diagnosed by an expert panel following
chest radiography, electrocardiography, echocardiography, and pul-
monary function tests. Not one patient had echocardiographic evi-
dence of isolated right HF. This corroborates reports estimating the
prevalence of cor pulmonale in chronic obstructive pulmonary
disease to be 0.2%.
94
There is a simple clinical message. Patients
with chronic obstructive pulmonary disease and suspected HF
must be considered to have left ventricular dysfunction until
proven otherwise.
Prevalence of left ventricular
systolic dysfunction in patients
with chronic obstructive
pulmonary disease
A recent systematic review identified 18 reports quantifying LVEF
among chronic obstructive pulmonary disease patients, most with
small numbers of participants (n¼10– 120).
57
The prevalence of
LVSD varied considerably, ranging from 10 to 46% in unselected
patients with stable chronic obstructive pulmonary disease.
Studies excluding patients with coronary disease observed a
lower prevalence of 0– 32%.
Relationship between chronic
obstructive pulmonary disease
and heart failure
Chronic obstructive pulmonary disease is characterized by low-grade
systemic inflammation, which may contribute to the progression of
atherosclerosis and adverse cardiovascular events.
95– 97
Myocardial
dysfunction may ensue. In the NHANES III survey, moderate to
severe airflow obstruction was associated with elevated inflammatory
markers and electrocardiographic ischaemia.
95
Reduced FEV
1
inde-
pendently predicts cardiovascular mortality in population studies
after adjusting for age, cigarette smoking, hypertension, cholesterol,
...............................................................................................................................................................................
Table 4 Prevalence of chronic obstructive pulmonary disease in heart failure trials
Reference nPrevalence chronic
obstructive pulmonary
disease (%)
LVEF (%) Trial Population
Parker
146
6797 7 35 SOLVD Community
Sharma
147
3044 9 40 ELITE II Community
Staszewsky
103
5010 13 ,40 Val-HeFT Community
Massie
148
1587 8 35 WATCH Community
Grancelli
149
1518 9 Any DIAL Community
NETWORK Investigators
150
1532 7 — NETWORK Mixed
Gheorghiade
151
319 10 40 ACTIV-CHF HF hospitalization
Cuffe
152
949 23 ,40 OPTIME-CHF HF hospitalization
HF, heart failure; LVEF, left ventricular ejection fraction.
Primary publication and subgroup analyses of the following studies searched: ACTIV-CHF, A-HeFT, AMIOVERT, AMTG, ANZ, ATLAS, ATTACH, BEST, CHANGE,
CAPRICORN, CARE-HF, CARMEN, CHARM, CHF-STAT, CHRISTMAS, CIBIS I, CIBIS II, CIBIS III, COMET, COMPANION, CONSENSUS, CONTAK-CD, COPERNICUS,
CORONA, DANREHAB, DECREASE-HF, DEFINITE, DIAMOND-CHF, DIG, EARTH, ECHOS, ELITE, ELITE II, ELVD, EMTG, EPOCH, EXERT, FACET, FIRST, GESICA, HEAT,
IMPRESS, LIDO, MACAS, MACH-1, MDC, MERIT-HF, MIRACLE, MIRACLE-ICD, MIRACLE-ICD II, MOCHA, MOXSE, MOXCON, MUSTIC, NETWORK, OPTIME-CHF,
OVERTURE, PATH-CHF, PATH-CHF II, PEP-CHF, PICO, PRAISE, PRECEDENT, PRECISE, PRIME II, PROMISE, RADIANCE, RALES, RAPID-CHF, REACH-1, REMATCH,
RENEWAL, RESOLVD, RETHINQ, REVERT, RITZ, SCD-HeFT, SENIORS, SOLVD, SURVIVE, SWORD, US Carvedilol Trials, VERITAS, VEST, V-HeFT I, V-HeFT II, V-HeFT III,
WASH, WATCH, and XISHF.
Heart failure and chronic obstructive pulmonary disease 135
and obesity.
98
A meta-analysis demonstrated an increased relative risk
of 1.75 (1.54–2.01) when comparing worst and best FEV
1
quintiles.
99
However, the multivariable models were often limited, notably
lacking adjustment for co-existing diabetes and cardiovascular disease.
Inflammation is itself implicated in the pathogenesis of HF. Inci-
dence of HF was greater in Framingham subjects with elevated C-
reactive protein and cytokine levels, independent of established
risk factors [hazard ratio (HR) 4.07; 95% CI 1.34– 12.37; P¼
0.01].
100
However, two population studies found no evidence of
a relationship between chronic obstructive pulmonary disease
and incidence of HF. The Cardiovascular Health Study prospec-
tively examined 5888 elderly subjects over a mean of 5.5 years.
Elevated C-reactive protein and reduced FEV
1
, but not a history
of chronic obstructive pulmonary disease, were significant factors
...............................................................................................................................................................................
Table 5 Prognostic implications of chronic obstructive pulmonary disease in patients with HF
Reference NPrevalence chronic
obstructive pulmonary
disease (%)
LVEF
(%)
Outcome Follow up Univariate
analysis
(+++++95% CI)
Multivariable
analysis
(+++++95% CI)
Gustafsson
80
5491 22 Any Death 1 year — RR 1.36 (1.25–1.47)
Sharma
147
3044 9 40 Death — RR 1.49 (1.15– 1.95)
P¼0.0049
RR 1.34 (1.02–1.75)
P¼0.0354
Lee
129
2624 21 Any Death 1 year OR 1.30 (1.07–
1.58) P¼0.009
OR 1.41 (1.13–
1.75) P¼0.003
Goldberg
125
2445 34 Any Death 1 year — OR 1.39 (1.15–
1.69)
Braunstein
114
122 630 26 Any Death 1 year RR 1.31 (1.27 – 1.34) RR 1.12 (1.09–1.16)
Alexander
153
90 316 — Any Death 1 year — RR 1.19 (1.15 – 1.22)
Jong
154
38 702 — Any Death 1 year — OR 1.13 (1.07 –
1.19) P,0.001
Krumholz
155
222 424 — Any Death 30 days — OR 1.15 (1.12 –
1.18)
Martinez-Selles
69
1065 30 Any Death Median 19
months
— HR 1.6 (1.2 – 2.0)
P¼0.001
Tribouilloy
142
294 21 ,50 Death 5 year — HR 1.49 (1.04– 1.95)
P¼0.05
Tribouilloy.
142
368 20 50 Death 5 year — HR 1.61 (1.13 –2.28)
P¼0.008
Senni
135
292 15 Any Death 1 year — OR 1.41 (0.99–
2.35) P¼0.005
Agoston
87
448 31 Any Death — — HR 1.45 (1.10– 1.92)
P¼0.01
Kjaergaard
86
388 22 Any Death — — HR 2.67 (1.98– 3.59)
P,0.0001
Kamalesh
124
495 52 Reduced Death — OR 1.59 (1.15–
2.19) P¼0.0048
OR 1.34 (0.95–
1.90) P¼0.095
Newton
131
528 9 Any Death Mean 1257 days HR 1.49 (1.00– 2.20)
P¼0.049
-, P¼NS
Siirila-Waris
137
620 13 Any Death 1 year HR 1.2 (0.80– 1.87)
P¼0.4
-, P¼NS
Macchia
70
1020 24 Any Death mean 287 days HR 1.46 (1.12– 1.92)
P¼0.005
HR 1.42 (1.09– 1.86)
P¼0.010
Macchia
70
1020 24 Any HF hospitalization,
MI, or stroke
Mean 244 days — HR 1.26 (1.01 –1.58)
P¼0.04
Ansari
72
403 26 Any Death or CV
hospitalization
Mean 22 months HR 1.32 (0.9 – 1.9)
P¼0.14
HR 1.39 (0.9–2.1)
P¼0.11
Berry
144
315 11 40 Death or HF
hospitalization
— — HF 1.61 (0.98 – 2.64)
P¼0.061
Parker
146
6797 7 35 Death or HF
hospitalization
— — OR 1.43 (1.16 –
1.76) P¼0.0008
Braunstein
114
122 630 26 Any HF hospitalization 1 year RR 1.49 (1.45 – 1.53) RR 1.40 (1.36 – 1.44)
Harjai
112
434 18 Any HF hospitalization 30 days — OR 2.2 (1.1 – 4.5)
CI, confidence interval; CV, cardiovascular; LVEF, left ventricular ejection fraction (‘Any’ denotes inclusion of all patients with heart failure); HF, heart failure; HR, hazard ratio;
MI, myocardial infarction; OR, odds ratio; RR, risk ratio.
N.M. Hawkins et al.136
during stepwise selection of variables in this study.
101
Likewise,
chronic obstructive pulmonary disease was not an independent
predictor of LVSD in the Copenhagen study.
102
Both studies
relied upon self-reported medical history. Such methods are par-
ticularly limited when examining conditions with diagnostic difficul-
ties and overlapping symptoms.
Prognostic implications of chronic
obstructive pulmonary disease
in patients with heart failure
Few studies focused on the prognosis of patients with HF and con-
comitant chronic obstructive pulmonary disease.
70,103
However,
chronic obstructive pulmonary disease was consistently an inde-
pendent predictor of death and HF hospitalization when reported
in multivariable models (Table 5). In many models the prognostic
significance approached or exceeded that of traditional factors
including male gender, diabetes, hypertension, NYHA class, and
anaemia. As in all multivariable analyses, the risk relates in part
to the number and type of variables adjusted for in the model.
Only one study has explored the causes of increased mortality.
103
The outcomes of patients with chronic obstructive pulmonary
disease enrolled in the Val-HeFT trial were examined using multi-
variate models including demographic, clinical, biohumoral, and
treatment variables. Chronic obstructive pulmonary disease
strongly predicted non-cardiovascular mortality (HR 2.50 [1.58–
3.96], P,0.0001) and hospitalizations (HR 1.71 [1.43– 2.06],
P,0.0001), but not cardiovascular death or hospitalizations.
The relationship between chronic obstructive pulmonary disease
and ischaemic or arrhythmic events has never been reported in
patients with HF.
The increased risk of HF hospitalization is unsurprising. Respirat-
ory infections are associated with decompensation in 10– 16% of
admissions.
104 – 109
Concomitant chronic obstructive pulmonary
disease prolongs inpatient stay,
110,111
increases risk of readmis-
sion,
112 – 114
and independently predicts greater financial costs.
115
Respiratory disease, and in particular chronic obstructive pulmonary
disease, is a more frequently recorded comorbidity in winter.
116
The
ACC/AHA guidelines advocate influenza and pneumococcal immu-
nization to reduce this risk.
117
Administering influenza A vaccine to
elderly patients with HF during the 1991– 1992 influenza epidemic
reduced the rate of HF hospitalization by 37%, and associated
costs by 43%.
118
Conclusions
The combination of HF and chronic obstructive pulmonary disease
presents many diagnostic challenges. Clinical symptoms and signs
require careful interpretation, in conjunction with objective evi-
dence of each condition. Both are chronic progressive diseases
complicated by exacerbations. Physicians must consider the
timing of investigations within the disease trajectory. Over time,
LVSD may develop, or the severity of airflow obstruction increase.
Treatment will alter accordingly. Transthoracic echocardiography
is adequate in many patients, while magnetic resonance imaging
is the modality of choice in those with limited acoustic windows.
Airflow obstruction must be demonstrated when clinically euvo-
laemic. Inadequate assessment risks both misdiagnosis and inap-
propriate treatment.
Greater collaboration is required between cardiologists, pulmo-
nologists, and general practitioners. Both conditions are systemic
disorders with potentially overlapping pathophysiological pro-
cesses. The ‘fit’ of even complex multivariable HF models
remains imperfect. Part of this undefined risk may arise in the
lungs. The impact of chronic obstructive pulmonary disease on car-
diovascular outcomes is yet to be fully defined. In the meantime
cardiologists and pulmonologists, respectively, must better identify
and manage concurrent chronic obstructive pulmonary disease and
HF. The resulting symptomatic and prognostic benefits far out-
weigh those attainable by treating either condition alone.
Funding
Dr Hawkins thanks Heart Research UK for funding clinical research in
Stobhill Hospital.
Conflict of interest: none declared.
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