Original article 179
Heart failure diagnosis in acute conditions has high agreement with inpatient diagnosis Marie-France Serondea,g,*, Said Laribia,b,h,*, Sean P. Collinsi, Nicolas Deyea,c,h, Damien Logearta,d,f,h,j, Patrick Plaisancea,b,f,h, Alain Cohen-Solala,d,f,h,j and Alexandre Mebazaaa,e,f,h Objectives Acute heart failure (AHF) is frequently encountered in the emergency department (ED) or in the cardiac care unit (CCU)/ICU. Discrimination between cardiac and noncardiac cause of dyspnea by clinical means and standard testing is sometimes inadequate. The aim of our study was to assess AHF diagnosis agreement as determined by: (a) the attending physician, (b) the hospital discharge diagnosis, and (c) an adjudication committee. Patients and methods Between 2010 and 2011, consecutive patients arriving for dyspnea in our hospital were prospectively included. A convenience sample of patients was enrolled in this analysis. Patients were admitted through the ED (280 patients) or through CCU/ICU (112 patients) for undifferentiated dyspnea.
parameters utilizing B-type natriuretic peptide testing has high agreement and accuracy with the hospital discharge and adjudicated diagnosis of AHF. The present study also shows that the accuracy of the initial AHF diagnosis allows rapid inclusion in AHF trials. These results, if confirmed in a broader cohort of patients, suggest that the initial ED diagnosis is highly accurate and reliable to guide further inpatient management. European Journal of Emergency Medicine 23:179–184 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. European Journal of Emergency Medicine 2016, 23:179–184 Keywords: acute heart failure, adjudication, B-type natriuretic peptide, diagnosis, emergency department a
UMR-S 942 Inserm, bDepartment of Emergency Medicine, cIntensive Care Unit, Department of Cardiology, eDepartment of Anesthesiology and Intensive Care, f Paris Diderot University, Sorbonne Paris Cité, gDHU FIRE, Paris Diderot University, hAPHP, Saint Louis Lariboisière University Hospitals, Paris, i Department of Cardiology, EA3920, University Hospital Jean Minjoz, Besancon, France and jDepartment of Emergency Medicine, Vanderbilt University, Nashville, Tennessee, USA d
Results Overall, few differences were observed between the initial diagnosis and the hospital discharge diagnosis or the adjudicated diagnosis. Among the 200 patients with an initial diagnosis of AHF, hospital discharge diagnosis confirmed AHF (alone or combined) in 191 (95.5%) patients and the adjudication committee confirmed AHF (alone or combined) in 196 (98%) patients. Conclusion Our study showed considerable agreement between different AHF diagnostic standards. An initial AHF diagnosis on the basis of clinical signs and biological
Introduction Acute heart failure (AHF) is a frequent cause of presentation to the emergency department (ED) and admission to the cardiac care unit (CCU)/ICU [1–3]. When patients present with shortness of breath (SOB), discrimination between cardiac and noncardiac cause of SOB by clinical means and standard testing is often inadequate [4,5]. Symptoms may be nonspecific, and physical findings are not sensitive enough to use as a basis for an accurate diagnosis, especially in the aged population or in patients with comorbidities [6–8]. Indeed, measurement of plasma natriuretic peptides improves the diagnostic accuracy of AHF, although levels of uncertainty persist, including when the plasma natriuretic levels are in the ‘gray zone’, or in patients with renal dysfunction [9–12]. The level of Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.euro-emergencymed.com). 0969-9546 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Correspondence to Said Laribi, MD, PhD, Hôpital Lariboisière, Service des Urgences, 2 rue Ambroise Paré, 75010 Paris, France Tel: + 33 6 62 88 95 54; fax: + 33 1 49 95 80 73; e-mail: [email protected] *Marie-France Seronde and Said Laribi contributed equally to the writing of this article. Received 11 October 2014 Accepted 22 December 2014
agreement between the very initial diagnosis made within the first few hours, when only limited clinical signs, biological parameters, and chest radiograph are available, and the hospital discharge diagnosis, when echocardiography or more sophisticated exams as well as treatment response are known, has not been studied extensively [13]. Because B-type natriuretic peptide (BNP) is now available in the EDs and aids diagnostic accuracy in cases of diagnostic uncertainty, we hypothesized that the diagnosis of AHF in the first hours is as accurate as the diagnosis made later. Our main hypothesis is that AHF diagnosis agreement is high between the initial diagnosis, the hospital discharge diagnosis, and the adjudicated diagnosis. The aim of our study was to assess the agreement among the initial AHF diagnosis made by the senior attending physician, the hospital discharge ‘final’ diagnosis, and the diagnosis made by an adjudicated committee in SOB patients. DOI: 10.1097/MEJ.0000000000000247
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180 European Journal of Emergency Medicine 2016, Vol 23 No 3
Patients and methods
Statistical analysis
Study design and setting
The initial analysis compared the characteristics of patients with AHF, non-AHF, and a combined cause of SOB in the total population according to the initial diagnosis. Patients’ data were compared according to the diagnostic concordance between the three diagnostic standards. Values are expressed as means and SD, or counts and percentages as appropriate. Diagnostic groups were compared using a one-way analysis of variance and χ2test as appropriate. Variables not normally distributed were log transformed before statistical analysis. All other analyses are exploratory and utilized a two sided P-value of 0.05 for significance. For binary analysis of AHF versus noncardiac dyspnea, the group with a combined cause of SOB was included in the AHF group. To assess agreement between diagnostic assignments, we used Cohen’s κ coefficient [15, 16]. Statistics were calculated using the SPSS software, version 17 (SPSS Inc., Chicago, Illinois, USA).
The present study was a secondary analysis from the ‘biomarcoeurs’ cohort, described previously [14]. Briefly, between 2010 and 2011, consecutive patients arriving for SOB at Lariboisiere hospital were prospectively included. A convenience sample of patients who fulfilled the following criteria were enrolled in this analysis: (a) unscheduled hospitalization for SOB, (b) measurement of plasma BNP at arrival, and (c) hospital admission after ED visit or direct admission to the CCU or ICU. Of note, patients admitted to CCU/ICU were hospitalized in those units directly through the emergency medical services. No patient transferred from another hospital was included in this analysis. All study patients were included in the present study within 6 h after ED arrival or CCU/ICU admission. This investigation conforms to the principles outlined in the Declaration of Helsinki. The study was approved by the local institutional review board. All patients provided informed consent. This study was registered in clinicaltrials.gov and the identifier is NCT01374880.
Determination of diagnostic assignments
We compared three different diagnostic assignments: (a) the initial diagnosis; (b) the hospital discharge diagnosis; and (c) the adjudicated diagnosis. The initial diagnosis of the cause of SOB was made within 6 h of admission by the first senior physician in charge of the patient. The attending physician examined the patient and reviewed the available medical records as needed. As soon as the chest radiograph and BNP results were available, the physician then indicated whether the patient’s SOB was related to AHF only (AHF), to a noncardiac cause only (non-AHF), or to AHF combined with another non-AHF diagnosis (combined). The hospital discharge diagnosis was established by reviewing the medical record after hospital discharge. Only diseases quoted as the primary diagnosis were quoted as hospital discharge diagnosis and only if AHF was the primary diagnosis was it counted as an affirmative. Just an HF diagnosis reflected as a comorbidity in a secondary diagnosis did not count. The adjudicated diagnosis was made at least 1 month after hospital discharge by at least two HF experts (a senior cardiologist and a senior intensivist/emergency physician) not in charge of those patients and blinded to the initial and hospital discharge diagnosis. Experts had access to the material available in the ED or in the CCU/ICU and to the material available during the entire hospitalization. In the rare situation where the two HF experts were unable to reach an agreement, a third cardiologist adjudicated.
Results Characteristic of the study participants
Our study included 455 patients admitted for unscheduled and undifferentiated SOB. Sixty-three patients were excluded as plasma BNP was not measured at arrival by the attending physician. The studied population thus included 392 patients, of whom 280 were initially evaluated in the ED and 112 were directly hospitalized in the CCU (n = 101) or ICU (n = 11) (Fig. 1). At the initial site of admission, the initial diagnosis as determined by the attending physician diagnosed 200 (51%) patients with AHF, 139 (35.4%) as non-AHF, and 53 (13.5%) as a combined diagnosis. Patients with a combined diagnosis were older and more frequently had a history of atrial fibrillation compared with the other two groups. Population characteristics are described in Table 1 using the initial diagnosis as the criterion standard. Comparison of characteristics between those evaluated in the ED or CCU/ICU is shown in Supplementary Table S1 (Supplemental digital content 1, http://links.lww.com/EJEM/A87). Agreement of acute heart failure diagnosis
Overall, few differences were observed between the initial diagnosis and the hospital discharge diagnosis. Indeed, Fig. 2 shows that among the 200 patients with an initial diagnosis of AHF, hospital discharge diagnosis indicated AHF or combined in 191 (95.5%) patients; only nine (4.5%) were considered non-AHF. Among the 139 patients with an initial diagnosis of non-AHF, hospital discharge diagnosis indicated non-AHF in 119 (85.6%). AHF adjudicated diagnosis by experts showed a slightly greater number of concordant diagnosis compared with the hospital discharge diagnosis. Among 200 patients with an initial diagnosis of AHF, only four (2%) were considered as non-AHF in the adjudicated diagnosis. Supplementary Fig. S1 and S2 (Supplemental digital content 2, http://links.lww.com/EJEM/A89, Supplemental digital content 3, http://links.lww.com/EJEM/A90).
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AHF: high agreement with inpatient diagnosis Seronde et al. 181
Fig. 1
455 patients with SOB
63 patients without plasma BNP at admission
392 patients with plasma BNP at admission
280 patients admitted through the ED
112 patients admitted through CCU or ICU
Flow chart of the study population. BNP, B-type natriuretic peptide; CCU, cardiac care unit; ED, emergency department; SOB, shortness of breath.
Table 1
Characteristics of the study population Total population (n = 392)
Age [mean (SD)] (years) Male [n (%)] History of [n (%)] AF Coronary disease CHF Hypertension Diabetes Asthma COPD Clinical features HR [mean (SD)] (bpm) SBP [mean(SD)] (mmHg) DBP (mmHg) [mean (SD)] Respiratory rate/min [mean (SD)] Jugular vein distension [n (%)] Peripheral edema [n (%)] Rales [n (%)] Treatment at admission [n (%)] ACEI/ARB β-Blockers Statins Aldosterone antagonist β2 mimetic Biological features [mean (SD)] BNP (pg/ml) Creatinine (μmol/l) CRP (mg/l)
Non-AHF (n = 139)
Combined (n = 53)
P-value
73 (13) 235 (59.9)
72 (13) 136 (68)
72 (13) 72 (51.2)
81 (10) 27 (51)
0.5 0.1
132 110 140 240 109 51 82
(33.7) (28) (35.7) (61.2) (27.8) (13) (20.9)
76 59 105 129 66 13 12
(38) (29.5) (52.5) (64.5) (33) (6.5) (6)
28 33 12 80 28 30 54
(20) (23.7) (8.6) (57.6) (20.1) (21.6) (38.8)
28 18 23 31 15 8 16
(52.8) (34) (43.4) (58.5) (28.3) (15.3) (30.2)
0.03 0.5 < 0.001 0.6 0.09 0.009 < 0.001
93 140 79 29 123 187 376
(25) (25) (19) (7) (31.4) (47.7) (95.9)
85 140 82 28 85 116 196
(25) (30) (20) (7) (42.5) (58) (98)
98 142 78 30 23 40 128
(21) (28) (16) (7) (16.5) (28.8) (92)
95 130 74 31 20 31 52
(34) (31) (19) (6) (37.7) (58.5) (98.1)
0.05 0.4 0.006 0.8 0.001 0.004 0.7
208 155 135 51 64
(53) (39.5) (34.4) (13) (16.3)
125 99 84 34 13
(62.5) (49.5) (42) (17) (6.5)
55 32 34 13 43
(39.6) (23) (24.5) (9.3) (30.9)
28 24 17 4 8
(52.8) (45.3) (32) (7.5) (15)
0.03 0.002 0.05
1300 (2631) 116 (98) 52 (77)
AHF (n = 200)
1937 (3405) 126 (96) 27 (39)
365 (692) 103 (114) 67 (92)
1347 (1586) 118 (50) 92 (98)
0.002 < 0.001 0.03 < 0.001
Patients were classified in AHF, non-AHF, and combined on the basis of the initial diagnosis. Data are presented as mean ± SD. ACE, angiotensin-converting enzyme; AF, atrial fibrillation; ARB, angiotensin receptor blockers; BNP, brain natriuretic peptide; CHF, chronic heart failure; COPD, chronic obstructive pulmonary disease; CRP, C reactive protein; DBP, diastolic blood pressure; HR, heart rate; SBP, systolic blood pressure.
Clinical characteristics of concordant and discordant patients
Table 2 suggests that comorbidities, vitals, and laboratory values were not very helpful in distinguishing concordant and discordant cases. Compared with those with a
concordant initial/hospital discharge diagnosis, those with a discordant initial/hospital discharge diagnosis showed no significant difference in the parameters studied. Medical comorbidities and BNP levels were similar across both groups. Similar findings were observed in the
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182 European Journal of Emergency Medicine 2016, Vol 23 No 3
Fig. 2
Total population (n = 392) AHF n = 200
Initial diagnosis
Non-AHF n = 139
Combi 7
Combined n = 53
Hospital discharge diagnosis
AHF 184
Non-AHF 9
AHF 7
Non-AHF Combined AHF 119 13 10
Non-AHF 5
Combined 38
Adjudicated diagnosis
AHF 181
Non-AHF Combined AHF 4 15 15
Non-AHF Combined AHF 104 20 14
Non-AHF 9
Combined 30
Criterion standards comparison between initial and hospital discharge diagnosis and between initial and adjudicated diagnosis in the total population. AHF, acute heart failure.
Comparison of clinical, demographic, and biological characteristics among patients with a concordant and those with a discordant diagnosis between the initial diagnosis and the hospital discharge diagnosis
Table 2
Concordant diagnosis initial/hospital discharge (n = 341) Age [mean (SD)] 73 (years) Male [n (%)] 200 History of [n (%)] AF 110 Coronary disease 95 CHF 123 Hypertension 240 Diabetes 97 Asthma 48 COPD 70 Clinical features [mean (SD)] HR (bpm) 94 SBP (mmHg) 141 DBP (mmHg) 79 Treatment at admission [n (%)] ACEI/ARB 183 β-Blockers 133 Statins 114 β2 mimetic 59 Aldosterone 44 antagonist Biological features [mean (SD)] BNP (pg/ml) 1321 Creatinine (μmol/l) 118
Discordant diagnosis initial/hospital discharge (n = 51)
P-value
(13)
75 (14)
0.2
(58.7)
35 (68.6)
0.4
(32.3) (27.9) (36) (70.4) (28.4) (14) (20.5)
22 15 17 30 12 3 13
0.3 1.0 0.8 1 0.4 0.3 0.8
(26) (30) (19) (53.7) (39) (33.4) (17.3) (12.9)
(2759) (104)
(43.1) (29.4) (33.3) (58.8) (23.5) (5.8) (23.5)
92 (24) 137 (28) 76 (18) 25 22 21 5 7
(49) (43.1) (42) (9.8) (13.7)
1159 (1533) 106 (45)
0.4 0.6 0.2 0.7 0.7 0.4 0.3 1.0
0.7 0.4
Data are presented as mean ± SD. ACE, angiotensin-converting enzyme; AF, atrial fibrillation; ARB, angiotensin receptor blockers; BNP, brain natriuretic peptide; CHF, chronic heart failure; COPD, chronic obstructive pulmonary disease; DBP, diastolic blood pressure; HR, heart rate; SBP, systolic blood pressure.
initial/adjudicated diagnosis comparison; the only statistical difference observed between the two groups was related to renal function (Table S2, Supplemental Digital Content 1, http://links.lww.com/EJEM/A87).
Table 3 Levels of agreement between initial, hospital discharge, and adjudicated diagnosis Adjudicated diagnosis
Initial diagnosis Adjudicated diagnosis
Hospital discharge diagnosis
κ coefficient
95% CI
κ coefficient
95% CI
0.723
0.649–0.796
0.814 0.724
0.753–0.875 0.650–0.798
All studied patients (n = 392) were used to calculate the κ coefficient in this table. Patients were classified into two groups using the initial diagnosis: patients with heart failure [acute heart failure (AHF) or combined] or without HF (non-AHF). 95% CI, 95% confidence interval.
Agreement between diagnostic assignments
Table 3 shows the agreement between the different diagnostic assignments when comparing patients with heart failure (AHF or combined) and without HF (nonAHF): κ is equal to 0.814 [95% confidence interval (CI) 0.753–0.875] between initial and hospital discharge diagnosis; κ is equal to 0.723 (95% CI 0.649–0.796) between initial and adjudicated diagnosis and κ is equal to 0.724 (95% CI 0.650–0.798) between hospital discharge and adjudicated diagnosis. Similar results were found in the subgroup of patients with an initial diagnosis of AHF (Table S3, Supplemental Digital Content 1, http://links.lww.com/EJEM/A87). The diagnostic test characteristics for each diagnostic procedure assuming the others as the truth are shown in Table 4. The accuracy of both hospital discharge and adjudicated diagnosis for a prediction of an initial diagnosis of AHF were very good (0.902 and 0.848, respectively) although hospital discharge diagnosis appeared to have a better accuracy (P = 0.009). Similarly, the initial diagnosis was a better predictor of the hospital discharge
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AHF: high agreement with inpatient diagnosis Seronde et al. 183
Table 4
Diagnostic test characteristics for each of the diagnostic procedures Initial diagnosis
Initial diagnosis Accuracy Sensitivity Specificity Adjucated diagnosis Accuracy Sensitivity Specificity Hospital discharge diagnosis Accuracy Sensitivity Specificity
Adjudicated diagnosis
Hospital discharge diagnosis
P
0.848 (0.809–0.882) 87.3 (82.7–91) 88.9 (81.7–93.9)
0.902 (0.869–0.882) 92.3 (88.4–95.2) 90.2 (83.7–94.7)
0.009
0.875 (0.838–0.906) 93.9 (90.2–96.4) 76.5 (68.4–83.5)
0.74
0.881 (0.845–0.911) 94.9 (91.4–97.2) 74.8 (66.8–81.8) 0.912 (0.880–0.938) 94.9 (91.4–97.2) 85.6 (78.7–91)
0.852 (0.813–0.885) 88.7 (84.4–92.2) 86.6 (78.7–92)
0.003
The entire study population (n =392) was used to calculate diagnostic test characteristics. Patients were classified into two groups using the initial diagnosis: patients with heart failure [acute heart failure (AHF) or combined] or without HF (non-AHF).
diagnosis (0.912; P = 0.003) compared with the adjudicated diagnosis (0.881).
Discussion The initial diagnosis of AHF or non-AHF was found to be in high agreement with the hospital discharge diagnosis or the adjudicated diagnosis. However, although the initial diagnosis of AHF is very often correct, the diagnosis of AHF was missed in 15 (10.8%) patients; these patients were classified as non-AHF by the initial diagnosis, whereas the adjudicated diagnosis classified them as AHF. The first physicians to evaluate SOB patients in our study appear to have been more conservative, and labeled more AHF patients as non-AHF when they were initially diagnosed. The diagnosis of AHF by clinical means and standard testing is missed in about 20% [8,11]. Symptoms may not be specific to AHF, and physical findings are not sensitive enough to be used as a basis for an accurate diagnosis [17]. Previous studies suggest that BNP in the ED may be more accurate than any other finding from the history, physical exam, or diagnostic testing when determining the cause of dyspnea. BNP performed better than either the NHANES or the Framingham criteria, arguably the most widely accepted criteria for the diagnosis of AHF [11,18]. However, other recent studies have emphasized the risk of overdiagnosing HF only on the basis of high BNP values (gray zone and above), especially in the aged population, in patients with kidney dysfunction, or COPD patients [19,20].
hospital discharge and the adjudicated AHF diagnosis. An early accurate AHF diagnosis may improve the initial therapeutic management of these patients and may improve their outcomes. An accurate initial diagnosis is also important as it facilitates a smooth transition to a suitable specialty ward when inpatient management is needed [21,22]. Further, our inclusion of patients first evaluated in the ICU/CCU as part of the index group tests the accuracy of this unique European pattern of admission, and distinguishes this study from others. Another difference compared with previous studies is that adjudication was performed not only by cardiologists but also by other AHF experts, including intensivists and emergency physicians. A similar study has been carried out by Collins et al. [13]. Compared with the agreement that they found between the three criterion standards, our agreement was higher. This is surprising because in the previous study, experts were not blinded to the ED or hospital discharge diagnosis when reviewing charts. This may suggest that the initial diagnostic accuracy has improved, perhaps because of improved diagnostic testing, such as accurate BNP interpretation in indeterminate cases [23]. Our study further shows that renal dysfunction and not other factors such as older age was associated with discordance in AHF diagnosis. Further studies should explore factors associated with discordance in AHF diagnosis to help ED physicians in their daily practice.
Combined diagnosis was mentioned by three independent bodies: emergency physicians; cardiologists; and an adjudication committee. Indeed, combined diagnosis was roughly 15% of all acute dyspneic patients irrespective of the time of diagnosis. This cohort of patients is small, but it may be worthwhile exploring their impact on diagnostic agreement in a larger cohort.
Our study provides new perspectives in AHF trials [24–26]. From a clinical trial perspective, an early accurate AHF diagnosis may allow better screening of AHF patients and earlier inclusion in therapeutic trials. Trials are planning to include AHF patients as early as possible after hospital arrival, aiming to minimize delays in study drug administration. The present study shows that the accuracy of the initial AHF diagnosis may facilitate rapid inclusion in AHF trials [27,28].
In our study, BNP was incorporated into the initial diagnosis, which may be the reason for the high agreement between the initial AHF diagnosis and both the
This study has some limitations to consider when interpreting our results. This was a single-center study in a university hospital known as a referral center for HF
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184 European Journal of Emergency Medicine 2016, Vol 23 No 3
management. The results from our hospital may not be generalized to other settings. In our study, treating physicians did not follow a specific diagnostic protocol. Another limitation is that our study population was derived from all SOB patients where BNP was available. Our comparison may have yielded different results if a more undifferentiated group had been utilized, such as all SOB patients irrespective of BNP availability. Finally, as no sample size calculation was performed, we cannot exclude that the absence of a difference between concordant and discordant diagnosis (Table 2) might be related to an underpowered study. Despite these limitations, our study included a rather large number of patients. Conclusion
9
10
11
12
13
14
15
In summary, our study showed considerable agreement between different AHF diagnostic standards. An initial AHF diagnosis on the basis of clinical signs and biological parameters utilizing BNP testing has high agreement and accuracy with the hospital discharge and an adjudicated diagnosis of AHF. These results, if confirmed in a broader cohort of patients, suggest that the initial AHF diagnosis is highly accurate and reliable to guide further inpatient management and identify patients for inclusion in clinical trials.
16 17
18
19
20
Acknowledgements Conflicts of interest
There are no conflicts of interest.
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Heart failure diagnosis in acute conditions has high agreement with inpatient diagnosis Marie-France Serondea,g,*, Said Laribia,b,h,*, Sean P. Collinsi, Nicolas Deyea,c,h, Damien Logearta,d,f,h,j, Patrick Plaisancea,b,f,h, Alain Cohen-Solala,d,f,h,j and Alexandre Mebazaaa,e,f,h Objectives Acute heart failure (AHF) is frequently encountered in the emergency department (ED) or in the cardiac care unit (CCU)/ICU. Discrimination between cardiac and noncardiac cause of dyspnea by clinical means and standard testing is sometimes inadequate. The aim of our study was to assess AHF diagnosis agreement as determined by: (a) the attending physician, (b) the hospital discharge diagnosis, and (c) an adjudication committee. Patients and methods Between 2010 and 2011, consecutive patients arriving for dyspnea in our hospital were prospectively included. A convenience sample of patients was enrolled in this analysis. Patients were admitted through the ED (280 patients) or through CCU/ICU (112 patients) for undifferentiated dyspnea.
parameters utilizing B-type natriuretic peptide testing has high agreement and accuracy with the hospital discharge and adjudicated diagnosis of AHF. The present study also shows that the accuracy of the initial AHF diagnosis allows rapid inclusion in AHF trials. These results, if confirmed in a broader cohort of patients, suggest that the initial ED diagnosis is highly accurate and reliable to guide further inpatient management. European Journal of Emergency Medicine 23:179–184 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. European Journal of Emergency Medicine 2016, 23:179–184 Keywords: acute heart failure, adjudication, B-type natriuretic peptide, diagnosis, emergency department a
UMR-S 942 Inserm, bDepartment of Emergency Medicine, cIntensive Care Unit, Department of Cardiology, eDepartment of Anesthesiology and Intensive Care, f Paris Diderot University, Sorbonne Paris Cité, gDHU FIRE, Paris Diderot University, hAPHP, Saint Louis Lariboisière University Hospitals, Paris, i Department of Cardiology, EA3920, University Hospital Jean Minjoz, Besancon, France and jDepartment of Emergency Medicine, Vanderbilt University, Nashville, Tennessee, USA d
Results Overall, few differences were observed between the initial diagnosis and the hospital discharge diagnosis or the adjudicated diagnosis. Among the 200 patients with an initial diagnosis of AHF, hospital discharge diagnosis confirmed AHF (alone or combined) in 191 (95.5%) patients and the adjudication committee confirmed AHF (alone or combined) in 196 (98%) patients. Conclusion Our study showed considerable agreement between different AHF diagnostic standards. An initial AHF diagnosis on the basis of clinical signs and biological
Introduction Acute heart failure (AHF) is a frequent cause of presentation to the emergency department (ED) and admission to the cardiac care unit (CCU)/ICU [1–3]. When patients present with shortness of breath (SOB), discrimination between cardiac and noncardiac cause of SOB by clinical means and standard testing is often inadequate [4,5]. Symptoms may be nonspecific, and physical findings are not sensitive enough to use as a basis for an accurate diagnosis, especially in the aged population or in patients with comorbidities [6–8]. Indeed, measurement of plasma natriuretic peptides improves the diagnostic accuracy of AHF, although levels of uncertainty persist, including when the plasma natriuretic levels are in the ‘gray zone’, or in patients with renal dysfunction [9–12]. The level of Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.euro-emergencymed.com). 0969-9546 Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Correspondence to Said Laribi, MD, PhD, Hôpital Lariboisière, Service des Urgences, 2 rue Ambroise Paré, 75010 Paris, France Tel: + 33 6 62 88 95 54; fax: + 33 1 49 95 80 73; e-mail: [email protected] *Marie-France Seronde and Said Laribi contributed equally to the writing of this article. Received 11 October 2014 Accepted 22 December 2014
agreement between the very initial diagnosis made within the first few hours, when only limited clinical signs, biological parameters, and chest radiograph are available, and the hospital discharge diagnosis, when echocardiography or more sophisticated exams as well as treatment response are known, has not been studied extensively [13]. Because B-type natriuretic peptide (BNP) is now available in the EDs and aids diagnostic accuracy in cases of diagnostic uncertainty, we hypothesized that the diagnosis of AHF in the first hours is as accurate as the diagnosis made later. Our main hypothesis is that AHF diagnosis agreement is high between the initial diagnosis, the hospital discharge diagnosis, and the adjudicated diagnosis. The aim of our study was to assess the agreement among the initial AHF diagnosis made by the senior attending physician, the hospital discharge ‘final’ diagnosis, and the diagnosis made by an adjudicated committee in SOB patients. DOI: 10.1097/MEJ.0000000000000247
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180 European Journal of Emergency Medicine 2016, Vol 23 No 3
Patients and methods
Statistical analysis
Study design and setting
The initial analysis compared the characteristics of patients with AHF, non-AHF, and a combined cause of SOB in the total population according to the initial diagnosis. Patients’ data were compared according to the diagnostic concordance between the three diagnostic standards. Values are expressed as means and SD, or counts and percentages as appropriate. Diagnostic groups were compared using a one-way analysis of variance and χ2test as appropriate. Variables not normally distributed were log transformed before statistical analysis. All other analyses are exploratory and utilized a two sided P-value of 0.05 for significance. For binary analysis of AHF versus noncardiac dyspnea, the group with a combined cause of SOB was included in the AHF group. To assess agreement between diagnostic assignments, we used Cohen’s κ coefficient [15, 16]. Statistics were calculated using the SPSS software, version 17 (SPSS Inc., Chicago, Illinois, USA).
The present study was a secondary analysis from the ‘biomarcoeurs’ cohort, described previously [14]. Briefly, between 2010 and 2011, consecutive patients arriving for SOB at Lariboisiere hospital were prospectively included. A convenience sample of patients who fulfilled the following criteria were enrolled in this analysis: (a) unscheduled hospitalization for SOB, (b) measurement of plasma BNP at arrival, and (c) hospital admission after ED visit or direct admission to the CCU or ICU. Of note, patients admitted to CCU/ICU were hospitalized in those units directly through the emergency medical services. No patient transferred from another hospital was included in this analysis. All study patients were included in the present study within 6 h after ED arrival or CCU/ICU admission. This investigation conforms to the principles outlined in the Declaration of Helsinki. The study was approved by the local institutional review board. All patients provided informed consent. This study was registered in clinicaltrials.gov and the identifier is NCT01374880.
Determination of diagnostic assignments
We compared three different diagnostic assignments: (a) the initial diagnosis; (b) the hospital discharge diagnosis; and (c) the adjudicated diagnosis. The initial diagnosis of the cause of SOB was made within 6 h of admission by the first senior physician in charge of the patient. The attending physician examined the patient and reviewed the available medical records as needed. As soon as the chest radiograph and BNP results were available, the physician then indicated whether the patient’s SOB was related to AHF only (AHF), to a noncardiac cause only (non-AHF), or to AHF combined with another non-AHF diagnosis (combined). The hospital discharge diagnosis was established by reviewing the medical record after hospital discharge. Only diseases quoted as the primary diagnosis were quoted as hospital discharge diagnosis and only if AHF was the primary diagnosis was it counted as an affirmative. Just an HF diagnosis reflected as a comorbidity in a secondary diagnosis did not count. The adjudicated diagnosis was made at least 1 month after hospital discharge by at least two HF experts (a senior cardiologist and a senior intensivist/emergency physician) not in charge of those patients and blinded to the initial and hospital discharge diagnosis. Experts had access to the material available in the ED or in the CCU/ICU and to the material available during the entire hospitalization. In the rare situation where the two HF experts were unable to reach an agreement, a third cardiologist adjudicated.
Results Characteristic of the study participants
Our study included 455 patients admitted for unscheduled and undifferentiated SOB. Sixty-three patients were excluded as plasma BNP was not measured at arrival by the attending physician. The studied population thus included 392 patients, of whom 280 were initially evaluated in the ED and 112 were directly hospitalized in the CCU (n = 101) or ICU (n = 11) (Fig. 1). At the initial site of admission, the initial diagnosis as determined by the attending physician diagnosed 200 (51%) patients with AHF, 139 (35.4%) as non-AHF, and 53 (13.5%) as a combined diagnosis. Patients with a combined diagnosis were older and more frequently had a history of atrial fibrillation compared with the other two groups. Population characteristics are described in Table 1 using the initial diagnosis as the criterion standard. Comparison of characteristics between those evaluated in the ED or CCU/ICU is shown in Supplementary Table S1 (Supplemental digital content 1, http://links.lww.com/EJEM/A87). Agreement of acute heart failure diagnosis
Overall, few differences were observed between the initial diagnosis and the hospital discharge diagnosis. Indeed, Fig. 2 shows that among the 200 patients with an initial diagnosis of AHF, hospital discharge diagnosis indicated AHF or combined in 191 (95.5%) patients; only nine (4.5%) were considered non-AHF. Among the 139 patients with an initial diagnosis of non-AHF, hospital discharge diagnosis indicated non-AHF in 119 (85.6%). AHF adjudicated diagnosis by experts showed a slightly greater number of concordant diagnosis compared with the hospital discharge diagnosis. Among 200 patients with an initial diagnosis of AHF, only four (2%) were considered as non-AHF in the adjudicated diagnosis. Supplementary Fig. S1 and S2 (Supplemental digital content 2, http://links.lww.com/EJEM/A89, Supplemental digital content 3, http://links.lww.com/EJEM/A90).
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AHF: high agreement with inpatient diagnosis Seronde et al. 181
Fig. 1
455 patients with SOB
63 patients without plasma BNP at admission
392 patients with plasma BNP at admission
280 patients admitted through the ED
112 patients admitted through CCU or ICU
Flow chart of the study population. BNP, B-type natriuretic peptide; CCU, cardiac care unit; ED, emergency department; SOB, shortness of breath.
Table 1
Characteristics of the study population Total population (n = 392)
Age [mean (SD)] (years) Male [n (%)] History of [n (%)] AF Coronary disease CHF Hypertension Diabetes Asthma COPD Clinical features HR [mean (SD)] (bpm) SBP [mean(SD)] (mmHg) DBP (mmHg) [mean (SD)] Respiratory rate/min [mean (SD)] Jugular vein distension [n (%)] Peripheral edema [n (%)] Rales [n (%)] Treatment at admission [n (%)] ACEI/ARB β-Blockers Statins Aldosterone antagonist β2 mimetic Biological features [mean (SD)] BNP (pg/ml) Creatinine (μmol/l) CRP (mg/l)
Non-AHF (n = 139)
Combined (n = 53)
P-value
73 (13) 235 (59.9)
72 (13) 136 (68)
72 (13) 72 (51.2)
81 (10) 27 (51)
0.5 0.1
132 110 140 240 109 51 82
(33.7) (28) (35.7) (61.2) (27.8) (13) (20.9)
76 59 105 129 66 13 12
(38) (29.5) (52.5) (64.5) (33) (6.5) (6)
28 33 12 80 28 30 54
(20) (23.7) (8.6) (57.6) (20.1) (21.6) (38.8)
28 18 23 31 15 8 16
(52.8) (34) (43.4) (58.5) (28.3) (15.3) (30.2)
0.03 0.5 < 0.001 0.6 0.09 0.009 < 0.001
93 140 79 29 123 187 376
(25) (25) (19) (7) (31.4) (47.7) (95.9)
85 140 82 28 85 116 196
(25) (30) (20) (7) (42.5) (58) (98)
98 142 78 30 23 40 128
(21) (28) (16) (7) (16.5) (28.8) (92)
95 130 74 31 20 31 52
(34) (31) (19) (6) (37.7) (58.5) (98.1)
0.05 0.4 0.006 0.8 0.001 0.004 0.7
208 155 135 51 64
(53) (39.5) (34.4) (13) (16.3)
125 99 84 34 13
(62.5) (49.5) (42) (17) (6.5)
55 32 34 13 43
(39.6) (23) (24.5) (9.3) (30.9)
28 24 17 4 8
(52.8) (45.3) (32) (7.5) (15)
0.03 0.002 0.05
1300 (2631) 116 (98) 52 (77)
AHF (n = 200)
1937 (3405) 126 (96) 27 (39)
365 (692) 103 (114) 67 (92)
1347 (1586) 118 (50) 92 (98)
0.002 < 0.001 0.03 < 0.001
Patients were classified in AHF, non-AHF, and combined on the basis of the initial diagnosis. Data are presented as mean ± SD. ACE, angiotensin-converting enzyme; AF, atrial fibrillation; ARB, angiotensin receptor blockers; BNP, brain natriuretic peptide; CHF, chronic heart failure; COPD, chronic obstructive pulmonary disease; CRP, C reactive protein; DBP, diastolic blood pressure; HR, heart rate; SBP, systolic blood pressure.
Clinical characteristics of concordant and discordant patients
Table 2 suggests that comorbidities, vitals, and laboratory values were not very helpful in distinguishing concordant and discordant cases. Compared with those with a
concordant initial/hospital discharge diagnosis, those with a discordant initial/hospital discharge diagnosis showed no significant difference in the parameters studied. Medical comorbidities and BNP levels were similar across both groups. Similar findings were observed in the
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182 European Journal of Emergency Medicine 2016, Vol 23 No 3
Fig. 2
Total population (n = 392) AHF n = 200
Initial diagnosis
Non-AHF n = 139
Combi 7
Combined n = 53
Hospital discharge diagnosis
AHF 184
Non-AHF 9
AHF 7
Non-AHF Combined AHF 119 13 10
Non-AHF 5
Combined 38
Adjudicated diagnosis
AHF 181
Non-AHF Combined AHF 4 15 15
Non-AHF Combined AHF 104 20 14
Non-AHF 9
Combined 30
Criterion standards comparison between initial and hospital discharge diagnosis and between initial and adjudicated diagnosis in the total population. AHF, acute heart failure.
Comparison of clinical, demographic, and biological characteristics among patients with a concordant and those with a discordant diagnosis between the initial diagnosis and the hospital discharge diagnosis
Table 2
Concordant diagnosis initial/hospital discharge (n = 341) Age [mean (SD)] 73 (years) Male [n (%)] 200 History of [n (%)] AF 110 Coronary disease 95 CHF 123 Hypertension 240 Diabetes 97 Asthma 48 COPD 70 Clinical features [mean (SD)] HR (bpm) 94 SBP (mmHg) 141 DBP (mmHg) 79 Treatment at admission [n (%)] ACEI/ARB 183 β-Blockers 133 Statins 114 β2 mimetic 59 Aldosterone 44 antagonist Biological features [mean (SD)] BNP (pg/ml) 1321 Creatinine (μmol/l) 118
Discordant diagnosis initial/hospital discharge (n = 51)
P-value
(13)
75 (14)
0.2
(58.7)
35 (68.6)
0.4
(32.3) (27.9) (36) (70.4) (28.4) (14) (20.5)
22 15 17 30 12 3 13
0.3 1.0 0.8 1 0.4 0.3 0.8
(26) (30) (19) (53.7) (39) (33.4) (17.3) (12.9)
(2759) (104)
(43.1) (29.4) (33.3) (58.8) (23.5) (5.8) (23.5)
92 (24) 137 (28) 76 (18) 25 22 21 5 7
(49) (43.1) (42) (9.8) (13.7)
1159 (1533) 106 (45)
0.4 0.6 0.2 0.7 0.7 0.4 0.3 1.0
0.7 0.4
Data are presented as mean ± SD. ACE, angiotensin-converting enzyme; AF, atrial fibrillation; ARB, angiotensin receptor blockers; BNP, brain natriuretic peptide; CHF, chronic heart failure; COPD, chronic obstructive pulmonary disease; DBP, diastolic blood pressure; HR, heart rate; SBP, systolic blood pressure.
initial/adjudicated diagnosis comparison; the only statistical difference observed between the two groups was related to renal function (Table S2, Supplemental Digital Content 1, http://links.lww.com/EJEM/A87).
Table 3 Levels of agreement between initial, hospital discharge, and adjudicated diagnosis Adjudicated diagnosis
Initial diagnosis Adjudicated diagnosis
Hospital discharge diagnosis
κ coefficient
95% CI
κ coefficient
95% CI
0.723
0.649–0.796
0.814 0.724
0.753–0.875 0.650–0.798
All studied patients (n = 392) were used to calculate the κ coefficient in this table. Patients were classified into two groups using the initial diagnosis: patients with heart failure [acute heart failure (AHF) or combined] or without HF (non-AHF). 95% CI, 95% confidence interval.
Agreement between diagnostic assignments
Table 3 shows the agreement between the different diagnostic assignments when comparing patients with heart failure (AHF or combined) and without HF (nonAHF): κ is equal to 0.814 [95% confidence interval (CI) 0.753–0.875] between initial and hospital discharge diagnosis; κ is equal to 0.723 (95% CI 0.649–0.796) between initial and adjudicated diagnosis and κ is equal to 0.724 (95% CI 0.650–0.798) between hospital discharge and adjudicated diagnosis. Similar results were found in the subgroup of patients with an initial diagnosis of AHF (Table S3, Supplemental Digital Content 1, http://links.lww.com/EJEM/A87). The diagnostic test characteristics for each diagnostic procedure assuming the others as the truth are shown in Table 4. The accuracy of both hospital discharge and adjudicated diagnosis for a prediction of an initial diagnosis of AHF were very good (0.902 and 0.848, respectively) although hospital discharge diagnosis appeared to have a better accuracy (P = 0.009). Similarly, the initial diagnosis was a better predictor of the hospital discharge
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AHF: high agreement with inpatient diagnosis Seronde et al. 183
Table 4
Diagnostic test characteristics for each of the diagnostic procedures Initial diagnosis
Initial diagnosis Accuracy Sensitivity Specificity Adjucated diagnosis Accuracy Sensitivity Specificity Hospital discharge diagnosis Accuracy Sensitivity Specificity
Adjudicated diagnosis
Hospital discharge diagnosis
P
0.848 (0.809–0.882) 87.3 (82.7–91) 88.9 (81.7–93.9)
0.902 (0.869–0.882) 92.3 (88.4–95.2) 90.2 (83.7–94.7)
0.009
0.875 (0.838–0.906) 93.9 (90.2–96.4) 76.5 (68.4–83.5)
0.74
0.881 (0.845–0.911) 94.9 (91.4–97.2) 74.8 (66.8–81.8) 0.912 (0.880–0.938) 94.9 (91.4–97.2) 85.6 (78.7–91)
0.852 (0.813–0.885) 88.7 (84.4–92.2) 86.6 (78.7–92)
0.003
The entire study population (n =392) was used to calculate diagnostic test characteristics. Patients were classified into two groups using the initial diagnosis: patients with heart failure [acute heart failure (AHF) or combined] or without HF (non-AHF).
diagnosis (0.912; P = 0.003) compared with the adjudicated diagnosis (0.881).
Discussion The initial diagnosis of AHF or non-AHF was found to be in high agreement with the hospital discharge diagnosis or the adjudicated diagnosis. However, although the initial diagnosis of AHF is very often correct, the diagnosis of AHF was missed in 15 (10.8%) patients; these patients were classified as non-AHF by the initial diagnosis, whereas the adjudicated diagnosis classified them as AHF. The first physicians to evaluate SOB patients in our study appear to have been more conservative, and labeled more AHF patients as non-AHF when they were initially diagnosed. The diagnosis of AHF by clinical means and standard testing is missed in about 20% [8,11]. Symptoms may not be specific to AHF, and physical findings are not sensitive enough to be used as a basis for an accurate diagnosis [17]. Previous studies suggest that BNP in the ED may be more accurate than any other finding from the history, physical exam, or diagnostic testing when determining the cause of dyspnea. BNP performed better than either the NHANES or the Framingham criteria, arguably the most widely accepted criteria for the diagnosis of AHF [11,18]. However, other recent studies have emphasized the risk of overdiagnosing HF only on the basis of high BNP values (gray zone and above), especially in the aged population, in patients with kidney dysfunction, or COPD patients [19,20].
hospital discharge and the adjudicated AHF diagnosis. An early accurate AHF diagnosis may improve the initial therapeutic management of these patients and may improve their outcomes. An accurate initial diagnosis is also important as it facilitates a smooth transition to a suitable specialty ward when inpatient management is needed [21,22]. Further, our inclusion of patients first evaluated in the ICU/CCU as part of the index group tests the accuracy of this unique European pattern of admission, and distinguishes this study from others. Another difference compared with previous studies is that adjudication was performed not only by cardiologists but also by other AHF experts, including intensivists and emergency physicians. A similar study has been carried out by Collins et al. [13]. Compared with the agreement that they found between the three criterion standards, our agreement was higher. This is surprising because in the previous study, experts were not blinded to the ED or hospital discharge diagnosis when reviewing charts. This may suggest that the initial diagnostic accuracy has improved, perhaps because of improved diagnostic testing, such as accurate BNP interpretation in indeterminate cases [23]. Our study further shows that renal dysfunction and not other factors such as older age was associated with discordance in AHF diagnosis. Further studies should explore factors associated with discordance in AHF diagnosis to help ED physicians in their daily practice.
Combined diagnosis was mentioned by three independent bodies: emergency physicians; cardiologists; and an adjudication committee. Indeed, combined diagnosis was roughly 15% of all acute dyspneic patients irrespective of the time of diagnosis. This cohort of patients is small, but it may be worthwhile exploring their impact on diagnostic agreement in a larger cohort.
Our study provides new perspectives in AHF trials [24–26]. From a clinical trial perspective, an early accurate AHF diagnosis may allow better screening of AHF patients and earlier inclusion in therapeutic trials. Trials are planning to include AHF patients as early as possible after hospital arrival, aiming to minimize delays in study drug administration. The present study shows that the accuracy of the initial AHF diagnosis may facilitate rapid inclusion in AHF trials [27,28].
In our study, BNP was incorporated into the initial diagnosis, which may be the reason for the high agreement between the initial AHF diagnosis and both the
This study has some limitations to consider when interpreting our results. This was a single-center study in a university hospital known as a referral center for HF
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184 European Journal of Emergency Medicine 2016, Vol 23 No 3
management. The results from our hospital may not be generalized to other settings. In our study, treating physicians did not follow a specific diagnostic protocol. Another limitation is that our study population was derived from all SOB patients where BNP was available. Our comparison may have yielded different results if a more undifferentiated group had been utilized, such as all SOB patients irrespective of BNP availability. Finally, as no sample size calculation was performed, we cannot exclude that the absence of a difference between concordant and discordant diagnosis (Table 2) might be related to an underpowered study. Despite these limitations, our study included a rather large number of patients. Conclusion
9
10
11
12
13
14
15
In summary, our study showed considerable agreement between different AHF diagnostic standards. An initial AHF diagnosis on the basis of clinical signs and biological parameters utilizing BNP testing has high agreement and accuracy with the hospital discharge and an adjudicated diagnosis of AHF. These results, if confirmed in a broader cohort of patients, suggest that the initial AHF diagnosis is highly accurate and reliable to guide further inpatient management and identify patients for inclusion in clinical trials.
16 17
18
19
20
Acknowledgements Conflicts of interest
There are no conflicts of interest.
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