700874

research-article2017
ACC0010.1177/2048872617700874European Heart Journal: Acute Cardiovascular CareJobs et al.

Original scientific paper

European Heart Journal: Acute Cardiovascular Care

Pneumonia and inflammation in 2018, Vol. 7(4) 362­–370

© The European Society of Cardiology 2017
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https://doi.org/10.1177/2048872617700874
DOI: 10.1177/2048872617700874
failure: a registry-based journals.sagepub.com/home/acc

analysis of 1939 patients

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Alexander Jobs1,2, Ronja Simon1, Suzanne de Waha1,2,
Kyrill Rogacev1,2, Alexander Katalinic3, Valentin Babaev3
and Holger Thiele1,2

Abstract
Background: The prognostic impact of pneumonia and signs of systemic inflammation in patients with acute
decompensated heart failure (ADHF) has not been fully elucidated yet. The aim of the present study was thus to
investigate the association of pneumonia and the inflammation surrogate C-reactive protein with all-cause mortality in
patients admitted for ADHF.
Methods: We analysed data of 1939 patients admitted for ADHF. Patients were dichotomised according to the
presence or absence of pneumonia. The primary endpoint of all-cause mortality was determined by death registry
linkage.
Results: In total, 412 (21.2%) patients had concomitant pneumonia. Median C-reactive protein levels were higher in
patients with compared to patients without pneumonia (24.9 versus 9.8 mg/l, respectively; P<0.001). All-cause mortality
was significantly higher in patients with pneumonia (P<0.001). In adjusted Cox regression models, pneumonia as well
as C-reactive protein were independently associated with in-hospital mortality. Only C-reactive protein remained as
independent predictor for long-term mortality.
Conclusion: Pneumonia is relatively common in ADHF and a predictor for in-hospital mortality. However, inflammation
in general seems to be more important than pneumonia itself for long-term prognosis. Compared to community-acquired
pneumonia studies, C-reactive protein levels were rather low and therefore pneumonia might be over-diagnosed in
ADHF patients.

Keywords
Acute decompensated heart failure, pneumonia, inflammation, C-reactive protein, prognosis

Date received: 3 November 2016; accepted: 2 March 2017; Final Disposition Set: 2 March 2017

Introduction
Heart failure is the leading cause of hospital admission
1University Heart Center Lübeck, Department of Cardiology, Angiology
among adults older than 65 years in western countries.1,2
and Intensive Care Medicine, Germany
The risk of death is considerably increased over a pro- 2German Center for Cardiovascular Research (DZHK), Partner Site

longed period after a heart failure hospitalisation.3 Several Hamburg/Kiel/Lübeck, Germany

factors have been identified that may precipitate an epi- 3Institute for Cancer Epidemiology eV, University of Lübeck, Germany

sode of acute decompensated heart failure (ADHF) leading

Corresponding author:
to hospital admission (i.e. arrhythmia, myocardial ischae- Alexander Jobs, University Heart Center Lübeck, Medical Clinic II,
mia, infection, uncontrolled hypertension, inadequate Ratzeburger Allee 160, 23538 Lübeck, Germany.
preadmission treatment and non-adherence to medications Email: alexander.jobs@uksh.de
Jobs et al. 363
or diet).4–6 In large registries, respiratory infection was one
of the most prevalent factors precipitating ADHF occur-
ring in 15% to 29% of cases4,7,8 and was independently
associated with inhospital mortality in some analyses.4,7
Diagnosing pneumonia is often challenging in patients
admitted for ADHF as dyspnoea and rales are cardinal
symptoms for both heart failure and pneumonia.9,10
Clinically diagnosing pneumonia becomes even more chal-
lenging in elderly patients because respiratory and non-
respiratory symptoms are less often reported in this subset
of patients.11 Based on current guidelines, the presence of
infiltrates demonstrated by chest radiograph or another
lung imaging modality is mandatory for the diagnosis of
community-acquired pneumonia.12–14 Moreover, infections
other than pneumonia may precipitate ADHF. Together
with leukocyte count, C-reactive protein (CRP) is the most
commonly used laboratory marker for inflammation and
infection. However, it is not specific for bacterial infections
and is also elevated in systemic inflammatory states such as
ADHF.15 In this registry-based analysis we aimed to inves-
tigate the prevalence of pneumonia and predictors for the
presence of pneumonia as well as its association with all-
cause mortality in comparison to the inflammation surro-
gate CRP in patients admitted with ADHF.
Methods
Patients
We identified all cases with the primary discharge diagno-
sis of heart failure according to the International Statistical
Classification of Diseases and Related Health Problems,
10th revision, German Modification (ICD-10) code I50.*
treated in our department between 1 April 2008 and 31
December 2014. Patients were included in the analysis if
they presented with ADHF and had a chest radiograph per-
formed within the first 24 hours after admission. In patients
with more than one hospitalisation, only the first hospitali-
sation defined as the index hospitalisation, was analysed.
The study was approved by the ethical review committee of
the University of Lübeck.
Data extraction and definitions
Data were extracted by retrospective chart review of pro-
spectively entered data. ADHF was diagnosed if two or
more of the following symptoms or signs were reported:
dyspnoea on minimal exertion or at rest/orthopnoea (New
York Heart Association (NYHA) ≥III), jugular venous dis-
tention, pulmonary rales, and bilateral oedema. Baseline
characteristics including age, gender, date of admission,
date of discharge, and laboratory values were extracted
directly from the hospital information system. Comorbidities
were obtained by reviewing discharge letters. Infiltrates
and pulmonary congestion were rated as absent, possibly
present, or definitely present according to reports by board-
certified radiologists. Possibly and definitely present were
combined to present for regression analysis. Pneumonia
was defined based on the documentation of ICD-10 codes
J15.* and J18.* and the presence of infiltrates on admission
chest radiograph. Worsening renal function was defined as
an increase in creatinine concentration of 1.5 or greater
times from baseline or 26.5 µmol/l or more within 48 hours,
as recently suggested.16
Mortality data
The primary endpoint of all-cause mortality was prospec-
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tively assessed via the death registry of the province of
Schleswig-Holstein. For patients who did not die, the end
of follow-up was defined as the latest documented contact,
i.e. either discharge from index hospitalisation, discharge
from the last local hospitalisation at the University Hospital
of Lübeck, or date of the death registry query.
Statistical analysis
The final study population consisted of patients meeting the
above-mentioned criteria and was dichotomised in patients
with and without pneumonia.
Categorical patient characteristics were summarised as
frequencies and compared using Pearson’s chi-square test.
Continuous variables were summarised as median with
interquartile range (IQR) and compared using the Wilcoxon
rank-sum test. The cumulative mortality rate was visualised
by means of a Kaplan–Meier plot and compared using the
log-rank test.
With regard to regression models, linearity assumption
for continuous predictors was tested using restricted cubic
spline functions. Predictors were dichotomised or log-
transformed in the case of violation. This was the case for
CRP, sodium, and leukocyte count. Due to the absence of
an established cut-off value for CRP its median was used
for dichotomisation. In contrast, the leukocyte count was
defined as pathological when it was less than 4000/µl or
greater than 12,000/µl and hyponatraemia was defined as a
sodium level less than 136 mmol/l.
Predictors for pneumonia were identified by means of
logistic regression analyses. Patient characteristics not
commonly used to aid pneumonia diagnosis (i.e. CRP, leu-
kocyte count, and radiological infiltrates) are presented in
Table 1 and are available on admission with less than 10%
missing values and a P value less than 0.05 in univariable
analysis were considered as candidate predictors in a step-
wise backward selection procedure. At each step, the pre-
dictor with the highest P value was excluded until only
predictors with P<0.05 remained in the final model.
Multivariable Cox regression models were used to
assess whether pneumonia, CRP, or infiltrates were inde-
pendently associated with all-cause mortality after
364 European Heart Journal: Acute Cardiovascular Care 7(4)

Table 1.  Patient characteristics.

Total No pneumonia Pneumonia P value

n=1939 n=1527 n=412
Demographics
  Age (years) 78 (71–84) 77 (70–84) 79 (71–86) 0.008
  Male sex 1024/1939 (53) 798/1527 (52) 226/412 (55) 0.38
Comorbidities
  Coronary artery disease 1108/1938 (57) 876/1526 (57) 232/412 (56) 0.73
  History of myocardial infarction 467/1939 (24) 355/1527 (23) 112/412 (27) 0.11
  Previous PCI 489/1937 (25) 388/1525 (25) 101/412 (25) 0.75
  Previous CABG 339/1939 (17) 277/1527 (18) 62/412 (15) 0.16
  Diabetes mellitus 744/1939 (38) 563/1527 (37) 181/412 (44) 0.01

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  Atrial fibrillation or flutter 1089/1939 (56) 863/1527 (57) 226/412 (55) 0.58
Echocardiography characteristics
  Ejection fraction  
  Normal 541/1272 (43) 442/1032 (43) 99/240 (41) 0.56
  Mild 176/1272 (14) 138/1032 (13) 40/240 (17)
  Moderate 191/1272 (15) 151/1032 (15) 38/240 (16)
  Severe 364/1272 (29) 301/1032 (29) 63/240 (26)
  Mitral regurgitation II–III 306/1196 (26) 249/976 (26) 57/220 (26) 0.97
  Tricuspid regurgitation II–III 369/1124 (33) 304/920 (33) 65/204 (32) 0.81
 COPD 334/1939 (17) 248/1527 (16) 86/412 (21) 0.03
Laboratory characteristics
 eGFR according to MDRD at baseline 56 (40–75) 57 (41–76) 52 (35–69) <0.001
(ml/min/1.73 m²)
 eGFR according to MDRD at baseline <60 ml/ 1088/1938 (56) 828/1526 (54) 260/412 (63) 0.002
min/1.73 m²
  Leukocyte count at baseline 8380 8070 9940 <0.001
(6730–10608) (6530–10098) (7610–13112)
  Pathological leukocyte count 345/1938 (18) 200/1526 (13) 145/412 (35) <0.001
  CRP at baseline 12.1 (4.6–28.7) 9.8 (3.8–22.3) 24.9 (10.8–59.5) <0.001
  Haemoglobin at baseline (g/dl) 122 (108–137) 124 (109–137) 120 (105–137) 0.008
  Sodium at baseline (mmal/L) 139 (136–141) 139 (136–141) 138 (135–141) 0.02
  Hyponatremia at baseline 441/1938 (23) 335/1526 (22) 106/412 (26) 0.12
  High-sensitive troponin T at baseline (ng/l) 31 (19–52) 30 (18–49) 38 (23–67) <0.001
 High-sensitive troponin T increase 38 (24–68) 35 (22–62) 46 (29–93) <0.001
⩾20% at baseline
Chest radiograph characteristics
  Chest radiograph biplane 491/1939 (25) 444/1527 (29) 47/412 (11) <0.001
  Pulmonary infiltration  
  No 958/1939 (49) 958/1527 (63) 0/412 (0) <0.001
  Possible 307/1939 (16) 188/1527 (12) 119/412 (29)  
  Definite 674/1939 (35) 381/1527 (25) 293/412 (71)  
  Pulmonary congestion  
  No 663/1934 (34) 569/1523 (37) 94/411 (23) <0.001
  Possible 33/1934 (2) 29/1523 (2) 4/411 (1)  
  Definite 1203/1934 (62) 896/1523 (59) 307/411 (75)  
  Oedema 35/1934 (2) 29/1523 (2) 6/411 (1)  
Treatment characteristics
  Length of stay (days) 9 (6–13) 8 (6–13) 10 (7–15) <0.001
  Worsening renal function 483/1938 (25) 344/1526 (23) 139/412 (34) <0.001
  ICU admission 364/1939 (19) 229/1527 (15) 135/412 (33) <0.001

Values are median (IQR) or n (%).

Number of missing values for categorical characteristics is indicated by n/N. The number of missing values for CRP, high-sensitive troponin T, and
other laboratory values is 42, 670, and 1, respectively.
Other continuous values do not have missing values.
CABG: coronary artery bypass surgery; COPD: chronic obstructive pulmonary disease; CRP: C-reactive protein; eGFR: estimated glomerular
filtration rate; ICU: intensive care unit; MDRD: modification of diet in renal disease study equation; PCI: percutaneous coronary intervention; WRF:
worsening renal function.
Jobs et al. 365

Table 2.  Predictors of pneumonia in logistic regression analysis before and after stepwise backward selection.

Pneumonia

  Univariable Multivariable

  OR (95% CI) P value OR (95% CI) P value

Age (per year) 1.01 (1.00–1.02) 0.012  
COPD (no versus yes) 1.36 (1.03–1.78) 0.028 1.37 (1.03–1.80) 0.026
Diabetes (no versus yes) 1.34 (1.08–1.67) 0.009  
eGFR according to MDRD at baseline 0.92 (0.88–0.96) <0.001 0.92 (0.88–0.97) 0.001
(per 10 ml/min/1.73 m²)
Haemoglobin (per g/dl) 0.94 (0.89–0.99) 0.013  
Pulmonary congestion in baseline 2.01 (1.57–2.59) <0.001 2.00 (1.56–2.57) <0.001

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chest radiograph (no versus yes)

Due to missing data in >10% of all patients the following variables were not included in logistic regression analyses: ejection fraction, mitral
regurgitation, tricuspid regurgitation, and high-sensitive troponin T.
CI: confidence interval; COPD: chronic obstructive pulmonary disease; eGFR: estimated glomerular filtration rate; MDRD: modification of diet in
renal disease study equation; OR: odds ratio.

adjustment for demographics, comorbidities as well as
laboratory and radiological findings available on admis-
sion presented in Table 1.
All statistical tests were two-sided and considered sig-
nificant if P<0.05. All statistical analyses were done using
R software (www.r-project.org; version 3.1.3).
Results
Patient characteristics
In total, 2180 unique patients diagnosed with ADHF hospi-
talised for three or more days were identified. Of these, 1939
patients (88.9%) had a chest radiograph within 24 hours after
admission and were included in the final analysis.
The cohort was dichotomised into 1527 (78.8%) patients
without and 412 patients (21.2%) with pneumonia. Baseline
characteristics are presented in Table 1. Patients with pneu-
monia were older and had a higher prevalence of comorbidi-
ties such as diabetes mellitus or chronic obstructive
pulmonary disease (COPD). Moreover, their chest radio-
graphs were less often performed biplane in the upright
position and more often showed pulmonary congestion.
However, radiologists reported infiltrates in 569 (37.3%)
patients without ICD-10 coded pneumonia as determined by
treating physicians. Baseline CRP did not differ between
these patients and patients without pneumonia and without
infiltrates (9.6, IQR 4.1–20.2 versus 9.9, IQR 3.8–24.5 mg/l;
P=0.26). The median baseline CRP was 12.1 (IQR 4.6–28.7)
mg/l in the total population and was higher in patients with
pneumonia compared to those without (24.9 versus 9.8
mg/l, respectively; P<0.001, Table 1). Considering patients
with pneumonia, 29% and 11% had a baseline CRP above
50 mg/l and 100 mg/l, respectively. Echocardiographic
characteristics did not differ between patients with and with-
out concomitant pneumonia.
Multivariable logistic regression analysis identified
COPD, estimated glomerular filtration rate (eGFR), and
pulmonary congestion as independent predictors for pneu-
monia (Table 2).
Clinical outcome
Median follow-up was 16 (IQR 5–35) months. In-hospital
mortality was 4.0% (n=78) and 753 patients (38.8%) died
within 3 years. Pneumonia was a marker of all-cause mor-
tality (hazard ratio (HR) 1.34, 95% confidence interval (CI)
1.13–1.58; P<0.001; Figure 1a).
Infiltrates were also associated with all-cause mortality
(HR 1.20, 95% CI 1.04–1.40; P=0.02). This association
was present for infiltrates reported as possibly present (HR
1.31, 95% CI 1.08–1.60; P=0.007) as well as definitely pre-
sent (HR 1.30, 95% CI 1.10–1.51; P=0.002, Figure 1b).
Considering only patients without pneumonia, infiltrates
were not associated with all-cause mortality (HR 1.17, 95%
CI 0.97–1.42; P=0.10).
Elevated CRP levels above the median were also linked to
all-cause mortality (HR 1.59, 95% CI 1.37–1.84; P<0.001).
In a stratified analysis, CRP was only associated with adverse
clinical outcome in patients without pneumonia (pneumonia:
HR 1.00, 95% CI 0.72–1.39; P=0.99; no pneumonia: HR
1.71, 95% CI 1.44–2.02; P<0.001, Figure 1c).
Predicted hazard ratios for all-cause mortality did not
increase linearly with increasing baseline CRP in a
restricted cubic spline model (Figure 2a) in contrast to the
logarithm of baseline CRP (Figure 2b), which was there-
fore used for regression analysis. In an adjusted logistic
regression model, pneumonia and the logarithm of base-
line CRP but not demonstrable infiltrates on baseline
chest radiograph were independently associated with in-
hospital mortality (Table 3). The logarithm of baseline
CRP was identified as the only significant predictor for
366 European Heart Journal: Acute Cardiovascular Care 7(4)

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Figure 1.  Kaplan–Meier analysis of all-cause mortality stratified for (a) diagnosis of pneumonia (no versus yes); (b) confidence of
infiltrate diagnosis (no infiltrate, possible infiltrate, or definite infiltrate); and (c) diagnosis of pneumonia (no versus yes) and baseline
C-reactive protein (below or equal to/above median).

long-term mortality in an adjusted Cox regression model
(Table 3).
Discussion
This retrospective cohort study demonstrates that pneumo-
nia is common in patients admitted for ADHF, occurs more
often in patients with pronounced comorbidities, and is
independently associated with in-hospital mortality but not
with long-term mortality.
Pneumonia occurred in 21.2% patients of our ADHF
cohort, which is in the range of reported frequencies in pre-
viously published analyses of large registries investigating
precipitating factors for ADHF (15.3–8.5% in the Organized
Program to Initiate Lifesaving Treatment in Hospitalized
Patients With Heart Failure (OPTIMIZE-HF), 28.2% in Get
Jobs et al. 367

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Figure 2.  Comparing predicted hazard ratios (HRs) for all-cause mortality on the continuous scale of C-reactive protein (CRP)
between estimation by restricted cubic spline function with 5 knots at 1.2, 5.1, 12.1, 25.7 and 105.2 mg/l in red and estimation by a
linear function in green. The HR of 1 was arbitrarily set to the median CRP value of 12.1 mg/l. (a) Restricted cubic spline function
of untransformed CRP levels shows a non-linear increase in predicted HRs with a ceiling effect at higher CRP levels. (b) Restricted
cubic spline function and linear function predicted similar HRs over the continuous scale of CRP after log transformation.

Table 3.  Odds and hazard ratios for in-hospital and long-term mortality, respectively, for pneumonia, log CRP, and infiltrates in
adjusted regression models.

Pneumonia Log (baseline CRP) Baseline infiltrates

  OR/HR (95% CI) P value OR/HR (95% CI) P value OR/HR (95% CI) P value
In-hospital mortality 1.91 (1.16–3.09) 0.009 1.66 (1.37–2.02) <0.001 1.01 (0.62–1.63) 0.980
Long-term mortality 1.15 (0.97–1.36) 0.117 1.18 (1.12–1.25) <0.001 1.11 (0.95–1.29) 0.184

CI: confidence interval; COPD: chronic obstructive pulmonary disease; CRP: C-reactive protein; eGFR: estimated glomerular filtration rate; HR:
hazard ratio; MDRD: modification of diet in renal disease study equation.

With The Guidelines-HF (GWTG-HF), and 29% in the
Spanish National Registry on Heart Failure (RICA)).4,7,8
However, if pneumonia is truly a precipitating factor for
ADHF or rather a superimposed complication cannot be
clearly determined.
Patients with pneumonia more often had COPD and pul-
monary congestion on baseline chest radiograph. Together
with eGFR, both factors were identified as independent
predictors for pneumonia in a multivariable logistic regres-
sion model. Interestingly, early experimental data indicated
that pulmonary congestion may facilitate the growth of
bacteria commonly seen in pneumonia (i.e. Streptococcus
pneumonia and Staphylococcus aureus).17,18 Moreover,
COPD and chronic kidney disease are known risk factors
for community-acquired pneumonia,19,20 which underlines
the plausibility of the current results.
Pneumonia as a precipitating factor was independently
associated with in-hospital mortality but not with mid-
term mortality in two large registries.4,7 Our analysis of
concomitant pneumonia in ADHF is in line with this
observation, as pneumonia was independently associated
with in-hospital mortality but not with long-term mortal-
ity after adjusting for demographics, comorbidities, labo-
ratory and radiographic characteristics.
Pneumonia is commonly diagnosed based on clinical
features suggestive of acute lower respiratory tract infec-
tion and demonstrable infiltrates on chest radiograph.12–14
In addition, the diagnosis is often aided by elevated CRP
368 European Heart Journal: Acute Cardiovascular Care 7(4)
levels. One major finding of our analysis is that infiltrates
were also reported in 37% of patients without pneumonia
and that baseline CRP did not differ in these patients com-
pared to patients without infiltrates. Unfortunately, clinical
signs and symptoms as well as antibiotic treatment could
not be assessed retrospectively. In summary, the diagnosis
of pneumonia and the decision for or against an antibiotic
therapy is challenging in ADHF despite available chest radi-
ograph findings. Interpretation of chest radiographs is well
known to have technical limitations and to be prone to inter-
observer and intraobserver variability.21,22 Assessing pulmo-
nary infiltration by means of a chest radiograph may be
hampered in ADHF due to pulmonary congestion. In line
with this, radiologists were not sure about infiltrate diagno-
sis in 16% of chest radiographs. Interestingly, the mortality
risk did not differ between confidences of infiltrate diagno-
sis (i.e. probably present versus definitely present).
CRP is commonly used to aid the diagnosis of pneumo-
nia. However, it may also indicate other infections or a sys-
temic inflammation independent of infections and is thus
rather unspecific. Chronic heart failure is known to be an
inflammatory state23,24 and it is very likely that this may
be even more pronounced in ADHF.15 The median value
of 12.1 mg/l (4.6–28.7) for baseline CRP in the current
analysis was almost identical to the median value of 12.6
mg/l (IQR 5.2–30.5) in the Acute Study of Clinical
Effectiveness of Nesiritide in Decompensated Heart Failure
(ASCEND-HF) biomarker substudy15 and very similar to
multiple other studies; for example 11.0 (IQR 4.9–14.6) in
the Value of Endothelin Receptor Inhibition with Tezosentan
in Acute Heart Failure Study (VERITAS),25 13.0 (IQR 3.9–
35.3) in the multimarker emergency dyspnoea risk score
(MARKED),26 and 13.0 mg/l (IQR 6.0–25.0) in the BASEL
study.27 In contrast to the findings of the ASCEND-HF bio-
marker substudy demonstrating no association of baseline
CRP with in-hospital or 30-day mortality,15 we observed an
association with long-term mortality, which is in accord-
ance with the BASEL study. Interestingly, in the BASEL
study, the Cox regression model was adjusted for similar
covariates (mainly demographics, comorbidities and
laboratory findings) as in our analysis,27 whereas the
ASCEND-HF biomarker substudy15 also adjusted for sys-
tolic blood pressure and clinical signs/symptoms of conges-
tion.4,7 Besides study design aspects, covariates in
regression models may also contribute to these different
results because admission blood pressure and clinical con-
gestion status are known to be predictive of mortality in
ADHF. The relationship between CRP on a continuous
scale and all-cause mortality was not linear but rather
showed a ceiling effect for increasing CRP values as was
recently reported for procalcitonin in a similar population.28
Procalcitonin is more specific for bacterial infections than
CRP and was of prognostic importance in a substudy of the
Placebo-Controlled Randomized Study of the Selective A1
Adenosine Receptor Antagonist Rolofylline for Patients
Hospitalized with Acute Decompensated Heart Failure and
Volume Overload to Assess Treatment Effect on Congestion
and Renal Function (PROTECT) trial despite the exclusion
of patients with antibiotic treatment.28 Joffe et al.29 com-
pared admission CRP levels between patients admitted for
ADHF to patients admitted for community-acquired pneu-
monia. While the CRP level in their ADHF population was
similar to ours (13.5±13.5 mg/l), it was considerably higher
in their pneumonia population (127±84 mg/l).29 Several
other studies investigating CRP for aiding community-
acquired pneumonia diagnosis found that most patients had
CRP levels above 50 mg/l or 100 mg/l on admission.
Moreover, such values were highly specific for the diagno-
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sis of community-acquired pneumonia.30–32 However, only
few patients had CRP values above these cut-offs (29% and
11%, respectively) and one might speculate that pneumonia
was a false positive diagnosis which probably led to unnec-
essary antibiotic treatment.
Taken together, diagnosing pneumonia in patients with
ADHF is challenging because clinical symptoms are very
difficult to discriminate between being caused by ADHF
or pneumonia, the interpretation of chest radiographs
regarding infiltrates is difficult in congested patients and
CRP may also be elevated due to the inflammatory state of
ADHF alone. Moreover, CRP levels observed in several
ADHF populations are rather low compared to CRP levels
in patients with community-acquired pneumonia. We
therefore speculate provocatively that pneumonia is gen-
erally over-diagnosed in the setting of ADHF. The results
of the IMPACT-EU trial (NCT02392689), which ran-
domly assigns patients to either procalcitonin-guided anti-
biotic treatment or usual care, might help to resolve this
uncertainty and improve antibiotic treatment decisions in
the future.
Limitations
Due to the retrospective design, our study has several impor-
tant limitations. First, chest radiographs were only analysed
from clinically driven written reports by board-certified
radiologists. Second, several important characteristics were
not recorded at all or had missing values and therefore can-
not be considered as covariate in our regression model (e.g.
systolic blood pressure, heart rate, breathing rate, urea,
NT-probrain natriuretic peptide, procalcitonin, and clinical
signs/symptoms of heart failure/pneumonia). Based on this
and general methodological limitations, the results of our
analysis have to be interpreted as exploratory and hypothe-
sis generating but may stimulate further research.
Conclusions
Concomitant pneumonia is relatively common in patients
with ADHF but its diagnosis is challenging in this set-
ting. Pneumonia is a marker of all-cause mortality and is
Jobs et al. 369
independently associated with in-hospital mortality but
not with long-term mortality. With respect to prognosis,
baseline CRP seems to be more important than pneumo-
nia. This is probably due to the fact that CRP covers other
types of infections and also the severity of inflammation
caused by ADHF itself. CRP levels are rather low com-
pared to CRP levels reported from community-acquired
pneumonia populations. We therefore speculated that
pneumonia is over-diagnosed in the setting of ADHF.
Conflict of interest
The authors declare that there is no conflict of interest.
Funding
This research received no specific grant from any funding agency
in the public, commercial, or not-for-profit sectors.
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