Predictors of in-hospital mortality in patients admitted to the
emergency department with cardiogenic pulmonary edema
Abstract
Background: Despite significant advances in the treatment of heart
failure, the prognosis of acute cardiogenic pulmonary edema (ACPE)
continues to be a serious problem. The objective of this study is to
determine the risk factors affecting in-hospital mortality in patients
with ACPE.
Methods: We enrolled 305 patients who were hospitalized with cardiogenic
pulmonary edema as a diagnosis. Clinical, biochemical and
echocardiographic variables were collected and analysed. The patients
were divided into two groups according to the presence of mortality.
Both groups were evaluated in terms of clinical features during
admission to the emergency department (ED) and factors affecting
in-hospital mortality.
Results: Forty-two patients died and the mortality rate was 13.8%. To
determine the factors affecting mortality, multiple logistic regression
analysis was performed. In the regression analysis, it was seen that age
at admission to the ED (OR:1.75, 95% CI 1.18-3.05, p:0.014), systolic
blood pressure (OR:0.95, 95% CI 0.31-0.98, p:0.040), presence of acute
myocardial infarction (OR:4.17, 95% CI 1.85-7.13, p:0.001), positive
troponin (OR:5.47, 95% Cl 1.07-7.46, p:0.011), atrial fibrillation
rhythm (OR;3.16, 95% CI 1.81-8.02, p:0.010), inotropic drug usage
(OR;5.61, 95% CI 1.87-9.24, p:0.013) increased in-hospital mortality.
Conclusion: Our findings might help clinicians in identifying patients
with poor prognosis early in the presence of identified risk factors.
Keywords: Cardiogenic pulmonary edema, Mortality, Emergency department,
Risk factors
What’s already known about this topic?
Acute pulmonary edema(ACPE) is one of the important clinical problems in
patients admitted to emergency department. ACPE is one of the common
causes of acute respiratory failure and and is associated with poor
in-hospital outcomes.
What does this article add?
We determined that advanced age, systolic blood pressure at admission,
elevated troponin levels, presence of acute myocardial infarction ,
atrial fibrillation rhythm and inotropic drug need were associated with
in-hospital mortality. Our findings might help clinicians in identifying
patients with poor prognosis early in the presence of identified risk
factors.
Review criteria: how did you gather, select and analyze the information
you considered in your review?
The data of the study were obtained from the hospital electronic
database.Clinical, biochemical and echocardiographic variables were
collected and analysed.
Message for the clinic: what is the ‘take-home’ message for the
clinician?
Specific clinical picture pattern plays an important role in terms of
predicting mortality.
Predictors of in-hospital mortality in patients admitted to the
emergency department with cardiogenic pulmonary edema
1. INTRODUCTION
Acute pulmonary edema (APE) is one of the important clinical problems in
patients admitted to emergency department (ED). Most patients in the
emergency setting with pulmonary edema have the acute cardiogenic
variety, resulting mainly from elevated left ventricle (LV)
end-diastolic pressure. Acute cardiogenic pulmonary edema (ACPE), which
is a subset of APE, is a common symptom of acute heart failure and often
results in acute decompensated heart failure (ADHF).1In the United States, approximately 1 million patients are hospitalized
annually due to ADHF, and its mortality rate is 4% according to the
data.2 Samsky et al. analyzed heart failure mortality
and readmission rates between 2005 and 2015. They detected that in the
United States, 3.8% of patients admitted with heart failure died during
hospitalization, and the rate of readmission was 19.9%
.3
In general, ACPE emerges suddenly with a dramatic clinical picture and
is associated with poor in-hospital outcomes. ACPE is one of the common
causes of acute respiratory failure. The primary objective in patients
with ACPE is to provide adequate tissue oxygenation to prevent the
development of organ dysfunction and multiple organ failure. Although
rapid recovery is achieved in many patients with standard medical
therapy such as vasodilators, diuretics, inotropic agents and
supplemental oxygen therapy, a group of patients do not respond to these
and develop hypoxemic respiratory failure. These patients need intensive
care due to accompanying hypercapnia and respiratory acidosis. The
objective of this study is to determine the risk factors affecting
in-hospital mortality in patients with ACPE.
2. MATERIALS AND METHODS
2.1. Patient selection
In this study, the data of the patients aged 18 years and older, who
were diagnosed with ACPE in tertiary ED in our hospital and hospitalized
between January 1, 2017 and December 31, 2019, were analyzed. The data
of the study were obtained from the hospital electronic database. Local
ethics committee approval was obtained for the study (Ethics committee
number: 2019/12-20).
The patients, whose records could not be completely reached, who were
transferred to another hospital, who had severe respiratory distress
caused by conditions other than ACPE (for example, pneumonia, severe
anemia, renal failure), who were exposed to chemicals (for example,
ammonia), who were pregnant, who had inflammatory and neoplastic
disease, who underwent cardiopulmonary resuscitation and who were under
18 years of age, were excluded from the study.
2.2. Data collection and processing
The patients’ demographic characteristics, vital signs at the time of
admission to ED, physical examination findings, complaints at the time
of admission, chronic diseases, chest X-ray and/or computed tomography
(CT) findings, electrocardiogram (ECG) findings, transthoracic
echocardiographic (ECHO) findings, laboratory results, mechanical
ventilation (MV) requirement, intensive care need, length of hospital
stay and in-hospital mortality rates were recorded. ECG, ECHO,
radiological imaging and laboratory tests were performed in all patients
following their admissions to ED. ECHO was performed by a cardiologist.
As the initial treatment procedure in the ED, the patients were treated
with oxygen therapy, intravenous (IV) morphine sulfate and IV furosemide
were administered, and IV nitroglycerine infusion was performed.
Hypotension was initially treated with dobutamine and/or noradrenaline.
While noninvasive ventilation support was provided to the patients with
persistent respiratory failure, intubation and MV were used in
refractory hypoventilation cases. Angiotensin-converting enzyme
inhibitors or angiotensin receptor antagonists and beta blockers were
added to the treatment in the subacute phase of the disease.
The patients were divided into two groups according to the presence of
mortality. Both groups were evaluated in terms of clinical features
during admission to ED and factors affecting in-hospital mortality.
2.3. Definition and Diagnosis
ACPE was defined as the presence of pulmonary alveolar/interstitial
congestion on chest X-ray and/or CT with at least two of the followings:
1) severe respiratory distress or worsening respiratory distress or
persistent severe dyspnea, orthopnea 2) rales in lungs 3) high jugular
venous pressure.4
Diagnosis of acute myocardial infarction (AMI) was established according
to the criteria set by the European Society of Cardiology
guidelines.5 Vascular lesions detected in the coronary
angiography of the patients were recorded. The presence of a lesion
causing 50% or more stenosis in any coronary artery was recorded as
significant stenosis. Hypertension was defined as systolic blood
pressure >140 mm Hg and/or diastolic blood pressure
>90 mm Hg, or antihypertensive drug use.
ECHO procedure was performed from parasternal and apical windows with
two-dimensional, M mode, color doppler, pulsed wave doppler and
tissue doppler imaging techniques.
ECHO measurements were performed based on the criteria recommended by
the American Society of Echocardiography.6
2.4. Outcome measures
The primary outcome measure was mortality rate of the patients admitted
to the hospital from ED. This was used to determine the in-hospital
mortality rate of the hospitalized patients. The secondary outcome was
the effectiveness of clinical features during admission to ED on
in-hospital mortality. Thus, the risk factors affecting mortality rate
in patients with ACPE were determined.
2.5. Statistical Analysis
Statistical analysis was performed using the Statistical Package for
Social Sciences (SPSS) for Windows 20 (IBM SPSS Inc., Chicago, IL).
While evaluating the study data, descriptive statistical methods
(percentage calculations, median, mean and standard deviation) were
calculated. Continuous variables were expressed as mean ± standard
deviation (SD), while categorical variables were expressed as
percentage. Normal distribution of the data was evaluated with
Kolmogorov-Smirnov test. Student’s t-test was used for the comparison of
normally distributed continuous variables, while Mann-Whitney U-test was
used for the comparison of non-normally distributed variables. Pearson’s
Chi-square or Fisher’s test was used to compare the categorical
variables. Univariate and multivariate logistic regression analysis was
performed to determine the relationship between in-hospital mortality
rate and possible clinical variables. Multivariate logistic regression
analysis was applied to the variables with p<0.1 in univariate
logistic regression analysis. Odds ratios and 95% confidence intervals
were used to predict the relationship between independent determinants
of hospital mortality rate. A value of p<0.05 was considered
significant in all comparisons.
3. RESULTS
305 patients were included in our study. The mean age of the patients
was 67±5 years; 57.4% (n=175) were male, and 42.6% (n=130) were
female. Demographic and clinical characteristics of the patients are
given in Table 1. In terms of vital signs, while there was no
statistical difference between the two groups in terms of heart rate,
oxygen saturation and body temperature, there was a statistically
significant difference in terms of systolic blood pressure
(p<0.05). The most common accompanying comorbidities were
determined as congestive heart failure and hypertension (76.4% and
64.9%, respectively). The patients, who died, had lower LV EF compared
to the survivors (p: 0.001). ECG and ECHO findings of the patients, who
died and survived, are shown in Table 2. Noninvasive MV was needed in
69.2% of the patients (n=211). Endotracheal intubation was needed in 98
(32.1%) patients. The mean follow-up period of the patients who
survived was 5±4 days, while the mean follow-up period of those who died
was 9±5 days.
Forty-two (13.8%) patients died. When the patients, who died and
survived, were compared; age, systolic blood pressure, atrial
fibrillation/flutter, high troponin level, EF, moderate-severe mitral
insufficiency and inotropic drug usage were found to be statistically
significant. To determine the factors affecting mortality, multiple
logistic regression analysis was performed (Table 3). In the regression
analysis, it was seen that age at admission to the ED (OR:1.75, 95% CI
1.18-3.05, p:0.014), systolic blood pressure (OR:0.95, 95% CI
0.31-0.98, p:0.040), presence of AMI (OR:4.17, 95% CI 1.85-7.13,
p:0.001), elevated troponin levels (OR:5.47, 95% Cl 1.07-7.46,
p:0.011), atrial fibrillation rhythm (OR;3.16, 95% CI 1.81-8.02,
p:0.010), inotropic drug usage (OR;5.61, 95% CI 1.87-9.24, p:0.013)
increased in-hospital mortality.
4. DISCUSSION
Despite significant advances in the treatment of heart failure, the
prognosis of ACPE continues to be a serious problem. Although acute
treatment of ACPE is similar in different heart diseases, diagnosis and
treatment strategies can differ significantly. Therefore, it is
important to evaluate the risk factors that will affect the early and
late prognosis of the patient in determining the best treatment strategy
for the patients who recovered from the acute event. In our study, we
found the in-hospital mortality rate as 13.8% following ACPE
development. We determined that advanced age, systolic blood pressure at
admission, elevated troponin levels, presence of AMI, atrial
fibrillation rhythm and inotropic drug need were associated with
in-hospital mortality. These findings suggest that specific clinical
picture pattern plays an important role in terms of predicting
mortality.
Acute heart failure, which includes different clinical conditions such
as acute decompensation of chronic heart failure, right ventricular
failure, cardiogenic shock, and APE, is associated with increased
mortality rates and hospitalization.7,8 In acute heart
failure, in-hospital mortality rate is 4-7%, 3-month mortality rate
after discharge is 7-11%, and readmission rate in the first 3 months is
around 25-30% .9 Previous studies revealed that
advanced age, severe LV dysfunction, acute coronary syndromes, blood
pressure at admission, presence of renal failure, inotropic drug need
and anemia were the main determinants of
mortality.10-12 In-hospital mortality in ADHF was
found to be associated with advanced age, high heart rate, hyponatremia,
hypotension, LV systolic dysfunction, increased blood urea nitrogen
level, creatinine, troponin or natriuretic
peptides.13,14 Fonarow et al. developed a risk score
for in-hospital mortality in patients hospitalized due to acute heart
failure. In this study, they found that age, systolic blood pressure,
blood urea nitrogen level and heart rate were independent predictors of
mortality.15 Similarly, our study revealed that age,
admission systolic blood pressure, positive troponin and the need for
inotropic agents were associated with in-hospital mortality. Moreover,
we observed that atrial fibrillation rhythm was an additional strong
predictor which had not been previously reported.
Most commonly, ACPE occurs with acute myocardial ischemia or infarction,
cardiomyopathy, valvular heart disease or hypertensive emergencies. AMI
is the most common cause of heart failure and pulmonary edema.
Myocardial muscle damage results in low cardiac reserve and an increase
in LV diastolic, venous and pulmonary capillary pressure. This results
in fluid extravasation into the interstitial and alveolar space. ACPE
constitutes 10-20% of acute heart failure syndromes, and mortality may
be higher especially when associated with AMI.16,17While the majority of the patients admitted with ACPE had normal or high
systolic blood pressure, only 5-8% of them were admitted with low
systolic blood pressure (<90 mmHg). If hypoperfusion findings
accompany, this group has a poor prognosis.18 In our
study, certain traditional cardiovascular risk factors in the general
population such as coexisting dyslipidemia and hypertension were not
associated with mortality. In contrast, atrial fibrillation was
associated with mortality in multivariate analysis. We found AMI in
9.5% (29) of the patients admitted with ACPE. We found the mortality
rate as 21.4% in the patients with AMI. The relationship between AMI
and high mortality rates in the patients admitted with ACPE may be
caused by severe LV systolic dysfunction. Early diagnosis and treatment
by evaluating the previous or concomitant cardiovascular disease, ECG
and ECHO findings in these patients may help reduce in-hospital
mortality.
It was revealed that noninvasive MV application in the treatment of
acute cardiogenic pulmonary edema reduced the need for endotracheal
intubation and mortality.19-22 In a meta-analysis
where standard oxygen therapy and noninvasive MV applications in the
patients with cardiogenic pulmonary edema were compared, hospital
mortality and intubation rates were significantly lower in the
noninvasive MV group compared to standard therapy
group.21,22 In our study, similar to other studies,
there was no significant difference in mortality in the patients who
received noninvasive MV in the ED.
This study has some limitations. The first limitation of the study was
the limited number of subjects fulfilling the inclusion criteria.
Secondly, the study is retrospective. The retrospective nature of the
study restricted data to those routinely collected. Our retrospective
study design may be related to selection biases, because this study only
included patients admitted to the hospital. Third, the study is
single-centered. The single-center study design carries inherent risks
of bias.
5. CONCLUSION
ACPE is a common condition in the ED and one of the most common causes
of hospitalization. We determined that age, systolic blood pressure at
admission, elevated troponin levels, AMI diagnosis, atrial fibrillation
rhythm and inotropic drug need were associated with in-hospital
mortality in the patients admitted with ACPE. Our findings might help
clinicians in identifying patients with poor prognosis early in the
presence of identified risk factors.
Acknowledgements: The authors thank all the participants in
this study