American Journal of Emergency Medicine 32 (2014) 1510–1512
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Brief Report
Diagnosing heart failure in children with congenital heart disease and respiratory syncytial virus bronchiolitis☆,☆☆,★ Nir Samuel, MD a,d, Tova Hershkovitz, MD b,d, Riva Brik, MD b,d, Avraham Lorber, MD c,d, Itai Shavit, MD a,d,⁎ a
Pediatric Emergency Department, Rambam Health Care Campus, Haifa Israel Department of Pediatrics B, Rambam Health Care Campus, Haifa Israel Pediatric Cardiology and Adults with Congenital Heart Disease, Rambam Health Care Campus, Haifa, Israel d Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel b c
a r t i c l e
i n f o
Article history: Received 15 August 2014 Received in revised form 29 August 2014 Accepted 1 September 2014
a b s t r a c t Objective: The objective of this study is to examine if the B-type natriuretic peptide (BNP) can be used in diagnosing heart failure (HF) in children with congenital heart disease (CHD) who present to the emergency department (ED) with acute bronchiolitis. Methods: A prospective cohort single-group study of children with CHD and respiratory syncytial virus bronchiolitis was conducted in a pediatric ED. The reference standard for the presence of HF was the clinical and echocardiographic assessment of a pediatric cardiologist blinded to the BNP test results. Results: Eighteen cases were diagnosed, 7 (39%) had acute HF and 11 (61%) did not have acute HF. Patients with HF had a higher level of BNP compared with patients who did not have HF (783 pg/mL [interquartile range, 70-1345] vs 59 pg/mL [interquartile range, 23-90]; P b .013). A BNP level of 95 pg/mL was the optimal cutoff point, having a sensitivity of 0.71 (95% confidence interval, 0.29-0.96) and a specificity of 0.91 (95% confidence interval, 0.58-0.99). Conclusion: The results of this small study suggest that the BNP test can be useful to ascertain the presence of HF in children with CHD who present to the ED with respiratory syncytial virus bronchiolitis. © 2014 Elsevier Inc. All rights reserved.
1. Introduction B-type natriuretic peptide (BNP) is a natriuretic hormone produced in response to myocardial pressure and shear stress. B-type natriuretic peptide plasma levels reflect the heart's volume and pressure loads [1]. In recent years, following studies in adults, BNP has been extensively studied in pediatrics for the early diagnosis of cardiac disease as well as assessment of heart failure (HF) in a multitude of clinical situations [1,2]. The diagnosis of pediatric HF in the emergency department (ED) is challenging due to nonspecific symptoms and signs [3]. A previous pediatric study compared noncardiac patients who presented with respiratory symptoms with cardiac patients who presented with HF and reported that the BNP can be a useful test to differentiate between the 2 groups [4]. ☆ Authors' contribution information: NS conceived the idea for the study, collected the data, reviewed the literature, and critically reviewed the manuscript; TH collected the data; RB and AL directed study implementation; and IS wrote the manuscript, analyzed the data, performed the statistical analysis, and reviewed the literature. NS has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. ☆☆ Conflict of interest: None declared. ★ Funding: None declared. ⁎ Corresponding author. Pediatric Emergency Department, Rambam Health Care Campus, 6 Ha'Aliya St, Bat Galim, Haifa, ISRAEL, 31096. Tel.: +972 50 2063239. E-mail address: [email protected] (I. Shavit). http://dx.doi.org/10.1016/j.ajem.2014.09.005 0735-6757/© 2014 Elsevier Inc. All rights reserved.
Infants and children with congenital heart disease (CHD) are at risk for developing HF when they have acute respiratory infections [5]. The objective of this study was to find out if the BNP can be used in diagnosing HF in children with CHD who present to the ED with respiratory syncytial virus (RSV) bronchiolitis. 2. Patients and methods 2.1. Study design A prospective cohort single-group study was conducted at the pediatric ED of Rambam Health Care Campus, a tertiary hospital in the north of Israel. During the study period, from October 1, 2010, to March 31, 2012, we enrolled patients with CHD and acute bronchiolitis. Patients were enrolled based on a convenience sample. The study was approved by the Rambam Health Care Campus Institutional Review Board. 2.2. Study protocol Children with known CHD who presented to the ED with a chief complaint of respiratory difficulty were eligible for enrollment. Congenital heart disease was defined as a known diagnosis of a congenital cardiac lesion as previously decided by a pediatric cardiologist. Once the diagnosis of acute bronchiolitis was established by the ED physician, study
N. Samuel et al. / American Journal of Emergency Medicine 32 (2014) 1510–1512
1511
researchers (NS and TH) were informed. Bronchiolitis was defined as an acute episode of cough, rhinorrhea, and wheezing or rales. Only patients with an RSV infection were included in the study. Respiratory syncytial virus infection was confirmed by a reverse transcription–polymerase chain reaction test from nasal secretions. Patients who were negative for the reverse transcription–polymerase chain reaction test were not included in the study. The following data were recorded by the study researcher on a designated structured form: age, sex, body temperature, patient's medications, admission department, and BNP level. During the next 12 hours, a cardiologist blinded to the BNP level examined the patient using echocardiography, verified the presence of CHD, and evaluated for the presence of HF. Hospital length of stay (LOS) was also recorded. 2.3. B-type natriuretic peptide test One milliliter of blood was collected into a tube containing potassium EDTA. B-type natriuretic peptide levels were determined using the AxSYM BNP assay (Abbott Laboratories, Abbott Park, IL).
Figure. Box-whisker plots for the median BNP levels in children with CHD who presented to the ED with RSV bronchiolitis (in picograms per milliliter).
2.4. Outcome measure The reference standard for the presence of HF was the clinical and echocardiographic assessment of a pediatric cardiologist blinded to the BNP results. 2.5. Statistical analysis Descriptive statistics are given as median with lower (25th percentile) and upper (75th percentile) quartiles. For comparison of BNP levels and hospital LOS, the Mann-Whitney U test was used. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for an optimal BNP cutoff point. Accuracy was calculated using the Wilcoxon estimate of area under receiver operating characteristic curve. All statistics were calculated using StatsDirect statistical software (version 2.6.6; StatsDirect Limited, Cheshire, UK). 3. Results During the study period, 28 children with CHD and respiratory distress were enrolled. Eighteen cases of acute RSV bronchiolitis were diagnosed and analyzed. All patients were admitted to hospital, and all recovered and were discharged. Anatomical defects comprised the majority of cardiac pathology affecting 66%, cardiomyopathies 22%, and repaired complex lesions 22%. Patients' mean age was 18 ± 4 months, mean temperature on ED admission was 38.1°C ± 0.9°C, and HF was assessed by 3 cardiologists. 3.1. Heart failure diagnosis in patients with CHD and RSV bronchiolitis (n = 18) Seven cases (39%) were diagnosed with HF by the cardiologists (Figure). These patients had a median BNP level of 783 pg/mL (interquartile range [IQR], 70-1345 pg/mL). Three patients were admitted to the pediatric intensive care unit (PICU). Overall hospital admission time was 15 days (IQR, 5-21 days). In 3 of the 7 cases, the cardiologist's assessment led to a change in pharmacological treatment; in 1 patient, the daily dosage of furosemide was increased; in 1 patient, furosemide and spironolactone were initiated; and 1 patient was placed on milrinone and dobutamine. Eleven cases (61%) were not diagnosed with HF. These patients had a median BNP level of 59 pg/mL (IQR, 23-90 pg/mL). Overall hospital admission time was 3 days (IQR, 2-4 days). None of the patients was admitted to the PICU. In 2 patients, the cardiologist increased the daily dosage of furosemide. In the other 9 cases, the cardiologist's assessment did not lead to a change in pharmacological treatment.
3.2. Comparison analysis Patients with HF had a higher level of BNP compared with patients who did not have HF (783 pg/mL [IQR, 70-1345] vs 59 pg/mL [IQR, 23-90]; P b .013). Patients with HF had a longer LOS compared with patients who did not have HF (15 days [IQR, 5-21] vs 3 days [IQR, 2-4]; P b .0036). 3.3. Receiver operating characteristics A BNP level of 95 pg/ml was determined to be the optimal cutoff point, having the highest accuracy (81.8%); sensitivity (95% confidence interval [CI]), 0.71 (0.29-0.96); specificity (95% CI), 0.91 (0.58-0.99); positive predictive value (95% CI), 0.83 (0.28-0.95); and negative predictive value (95% CI), 0.83 (0.26-0.93). 4. Discussion In this cohort of patients with CHD and acute RSV bronchiolitis, patients with HF had significantly higher levels of BNP compared with patients who did not have HF. Patients with HF had a median BNP level of 783 pg/mL (IQR, 70-1345), whereas patients who did not have HF had a median BNP level of 59 pg/mL (IQR, 23-90). This finding suggests that the BNP test can be used as a diagnostic marker of HF in this population of patients. We found that a BNP level of 95 pg/mL was the optimal cutoff point. When interpreting the results of the BNP test, clinicians should take into consideration the type of structural anomaly [4]. For example, plasma BNP levels are higher in patients with left ventricular volume overload compared with patients with right ventricular overload or pressure overload [4]. Young children who have comorbidity of CHD and RSV bronchiolitis are at increased risk for severe morbidity and even mortality [5]. The highest complication rate in infants with RSV bronchiolitis was reported in the subgroup of patients with CHD. These infants also had longer LOS and more PICU admissions [5]. The diagnosis of HF in these patients may be of help in the early assessment and management in the ED [3]. In our study, all patients recovered; however, the cohort who had HF had a significantly longer LOS, and 3 (43%) of 7 patients were admitted to the PICU. These findings suggest that patients with HF were more severely ill than patients who did not have HF and emphasize the importance of diagnosing HF in this high-risk population. In Israel, not all children with CHD are treated with an anti-RSV vaccine (palivizumab) because it is only partially funded by the ministry of
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health. All the patients in our study were not previously treated with palivizumab. This finding emphasizes the importance of the immunization against RSV in children with CHD. This pilot study is the first report on BNP in children with CHD and RSV infection. Our findings suggest that, when a young child with CHD presents to the ED with RSV bronchiolitis, his BNP level can be used to ascertain the presence of HF. If a high BNP level is detected, a diagnosis of HF is suspected, and a more severe disease course is expected. This is particularly important when a cardiology consult is not readily available and referral to an increased level of care may be warranted. Our study has several limitations. First, the small sample size possibly prevented proportional representation of different etiologies of CHD in this heterogeneous population. Second, a cardiologist's evaluation for HF was not performed immediately after ED admission but 4 to 12 hours later. Third, although cardiologists were practically blinded to the BNP level because only the researchers were informed about the BNP level, there was no formal blinding mechanism in this study. Fourth, because no baseline measurements were compared, this study is not able to determine if the BNP is
useful to distinguish ongoing chronic HF that is stable vs worsening HF or new onset HF. 5. Conclusion The results of this small cohort suggest that the BNP test can be useful to ascertain the presence of HF in children with CHD who present to the ED with RSV bronchiolitis. References [1] Das BB. Plasma B-type natriuretic peptides in children with cardiovascular diseases. Pediatr Cardiol 2010;31:1135–45. [2] Law YM, Hoyer AW, Reller MD, et al. Accuracy of plasma B-type natriuretic peptide to diagnose significant cardiovascular diseases in children: the Better Not Pout Children! Study. J Am Coll Cardiol 2009;541:1467–75. [3] Macicek SM, Macias CG, Jefferies JL, et al. Acute heart failure syndromes in the pediatric emergency department. Pediatrics 2009;124:e898-e904. [4] Koulouri S, Acherman RJ, Wong PC, et al. Utility of B-type natriuretic peptide in differentiating congestive heart failure from lung disease in pediatric patients with respiratory distress. Pediatr Cardiol 2004;25:34–6. [5] Willson DF, Landrigan CP, Horn SD, et al. Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. J Pediatr 2003;143(50):142–9.
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Brief Report
Diagnosing heart failure in children with congenital heart disease and respiratory syncytial virus bronchiolitis☆,☆☆,★ Nir Samuel, MD a,d, Tova Hershkovitz, MD b,d, Riva Brik, MD b,d, Avraham Lorber, MD c,d, Itai Shavit, MD a,d,⁎ a
Pediatric Emergency Department, Rambam Health Care Campus, Haifa Israel Department of Pediatrics B, Rambam Health Care Campus, Haifa Israel Pediatric Cardiology and Adults with Congenital Heart Disease, Rambam Health Care Campus, Haifa, Israel d Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel b c
a r t i c l e
i n f o
Article history: Received 15 August 2014 Received in revised form 29 August 2014 Accepted 1 September 2014
a b s t r a c t Objective: The objective of this study is to examine if the B-type natriuretic peptide (BNP) can be used in diagnosing heart failure (HF) in children with congenital heart disease (CHD) who present to the emergency department (ED) with acute bronchiolitis. Methods: A prospective cohort single-group study of children with CHD and respiratory syncytial virus bronchiolitis was conducted in a pediatric ED. The reference standard for the presence of HF was the clinical and echocardiographic assessment of a pediatric cardiologist blinded to the BNP test results. Results: Eighteen cases were diagnosed, 7 (39%) had acute HF and 11 (61%) did not have acute HF. Patients with HF had a higher level of BNP compared with patients who did not have HF (783 pg/mL [interquartile range, 70-1345] vs 59 pg/mL [interquartile range, 23-90]; P b .013). A BNP level of 95 pg/mL was the optimal cutoff point, having a sensitivity of 0.71 (95% confidence interval, 0.29-0.96) and a specificity of 0.91 (95% confidence interval, 0.58-0.99). Conclusion: The results of this small study suggest that the BNP test can be useful to ascertain the presence of HF in children with CHD who present to the ED with respiratory syncytial virus bronchiolitis. © 2014 Elsevier Inc. All rights reserved.
1. Introduction B-type natriuretic peptide (BNP) is a natriuretic hormone produced in response to myocardial pressure and shear stress. B-type natriuretic peptide plasma levels reflect the heart's volume and pressure loads [1]. In recent years, following studies in adults, BNP has been extensively studied in pediatrics for the early diagnosis of cardiac disease as well as assessment of heart failure (HF) in a multitude of clinical situations [1,2]. The diagnosis of pediatric HF in the emergency department (ED) is challenging due to nonspecific symptoms and signs [3]. A previous pediatric study compared noncardiac patients who presented with respiratory symptoms with cardiac patients who presented with HF and reported that the BNP can be a useful test to differentiate between the 2 groups [4]. ☆ Authors' contribution information: NS conceived the idea for the study, collected the data, reviewed the literature, and critically reviewed the manuscript; TH collected the data; RB and AL directed study implementation; and IS wrote the manuscript, analyzed the data, performed the statistical analysis, and reviewed the literature. NS has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. ☆☆ Conflict of interest: None declared. ★ Funding: None declared. ⁎ Corresponding author. Pediatric Emergency Department, Rambam Health Care Campus, 6 Ha'Aliya St, Bat Galim, Haifa, ISRAEL, 31096. Tel.: +972 50 2063239. E-mail address: [email protected] (I. Shavit). http://dx.doi.org/10.1016/j.ajem.2014.09.005 0735-6757/© 2014 Elsevier Inc. All rights reserved.
Infants and children with congenital heart disease (CHD) are at risk for developing HF when they have acute respiratory infections [5]. The objective of this study was to find out if the BNP can be used in diagnosing HF in children with CHD who present to the ED with respiratory syncytial virus (RSV) bronchiolitis. 2. Patients and methods 2.1. Study design A prospective cohort single-group study was conducted at the pediatric ED of Rambam Health Care Campus, a tertiary hospital in the north of Israel. During the study period, from October 1, 2010, to March 31, 2012, we enrolled patients with CHD and acute bronchiolitis. Patients were enrolled based on a convenience sample. The study was approved by the Rambam Health Care Campus Institutional Review Board. 2.2. Study protocol Children with known CHD who presented to the ED with a chief complaint of respiratory difficulty were eligible for enrollment. Congenital heart disease was defined as a known diagnosis of a congenital cardiac lesion as previously decided by a pediatric cardiologist. Once the diagnosis of acute bronchiolitis was established by the ED physician, study
N. Samuel et al. / American Journal of Emergency Medicine 32 (2014) 1510–1512
1511
researchers (NS and TH) were informed. Bronchiolitis was defined as an acute episode of cough, rhinorrhea, and wheezing or rales. Only patients with an RSV infection were included in the study. Respiratory syncytial virus infection was confirmed by a reverse transcription–polymerase chain reaction test from nasal secretions. Patients who were negative for the reverse transcription–polymerase chain reaction test were not included in the study. The following data were recorded by the study researcher on a designated structured form: age, sex, body temperature, patient's medications, admission department, and BNP level. During the next 12 hours, a cardiologist blinded to the BNP level examined the patient using echocardiography, verified the presence of CHD, and evaluated for the presence of HF. Hospital length of stay (LOS) was also recorded. 2.3. B-type natriuretic peptide test One milliliter of blood was collected into a tube containing potassium EDTA. B-type natriuretic peptide levels were determined using the AxSYM BNP assay (Abbott Laboratories, Abbott Park, IL).
Figure. Box-whisker plots for the median BNP levels in children with CHD who presented to the ED with RSV bronchiolitis (in picograms per milliliter).
2.4. Outcome measure The reference standard for the presence of HF was the clinical and echocardiographic assessment of a pediatric cardiologist blinded to the BNP results. 2.5. Statistical analysis Descriptive statistics are given as median with lower (25th percentile) and upper (75th percentile) quartiles. For comparison of BNP levels and hospital LOS, the Mann-Whitney U test was used. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for an optimal BNP cutoff point. Accuracy was calculated using the Wilcoxon estimate of area under receiver operating characteristic curve. All statistics were calculated using StatsDirect statistical software (version 2.6.6; StatsDirect Limited, Cheshire, UK). 3. Results During the study period, 28 children with CHD and respiratory distress were enrolled. Eighteen cases of acute RSV bronchiolitis were diagnosed and analyzed. All patients were admitted to hospital, and all recovered and were discharged. Anatomical defects comprised the majority of cardiac pathology affecting 66%, cardiomyopathies 22%, and repaired complex lesions 22%. Patients' mean age was 18 ± 4 months, mean temperature on ED admission was 38.1°C ± 0.9°C, and HF was assessed by 3 cardiologists. 3.1. Heart failure diagnosis in patients with CHD and RSV bronchiolitis (n = 18) Seven cases (39%) were diagnosed with HF by the cardiologists (Figure). These patients had a median BNP level of 783 pg/mL (interquartile range [IQR], 70-1345 pg/mL). Three patients were admitted to the pediatric intensive care unit (PICU). Overall hospital admission time was 15 days (IQR, 5-21 days). In 3 of the 7 cases, the cardiologist's assessment led to a change in pharmacological treatment; in 1 patient, the daily dosage of furosemide was increased; in 1 patient, furosemide and spironolactone were initiated; and 1 patient was placed on milrinone and dobutamine. Eleven cases (61%) were not diagnosed with HF. These patients had a median BNP level of 59 pg/mL (IQR, 23-90 pg/mL). Overall hospital admission time was 3 days (IQR, 2-4 days). None of the patients was admitted to the PICU. In 2 patients, the cardiologist increased the daily dosage of furosemide. In the other 9 cases, the cardiologist's assessment did not lead to a change in pharmacological treatment.
3.2. Comparison analysis Patients with HF had a higher level of BNP compared with patients who did not have HF (783 pg/mL [IQR, 70-1345] vs 59 pg/mL [IQR, 23-90]; P b .013). Patients with HF had a longer LOS compared with patients who did not have HF (15 days [IQR, 5-21] vs 3 days [IQR, 2-4]; P b .0036). 3.3. Receiver operating characteristics A BNP level of 95 pg/ml was determined to be the optimal cutoff point, having the highest accuracy (81.8%); sensitivity (95% confidence interval [CI]), 0.71 (0.29-0.96); specificity (95% CI), 0.91 (0.58-0.99); positive predictive value (95% CI), 0.83 (0.28-0.95); and negative predictive value (95% CI), 0.83 (0.26-0.93). 4. Discussion In this cohort of patients with CHD and acute RSV bronchiolitis, patients with HF had significantly higher levels of BNP compared with patients who did not have HF. Patients with HF had a median BNP level of 783 pg/mL (IQR, 70-1345), whereas patients who did not have HF had a median BNP level of 59 pg/mL (IQR, 23-90). This finding suggests that the BNP test can be used as a diagnostic marker of HF in this population of patients. We found that a BNP level of 95 pg/mL was the optimal cutoff point. When interpreting the results of the BNP test, clinicians should take into consideration the type of structural anomaly [4]. For example, plasma BNP levels are higher in patients with left ventricular volume overload compared with patients with right ventricular overload or pressure overload [4]. Young children who have comorbidity of CHD and RSV bronchiolitis are at increased risk for severe morbidity and even mortality [5]. The highest complication rate in infants with RSV bronchiolitis was reported in the subgroup of patients with CHD. These infants also had longer LOS and more PICU admissions [5]. The diagnosis of HF in these patients may be of help in the early assessment and management in the ED [3]. In our study, all patients recovered; however, the cohort who had HF had a significantly longer LOS, and 3 (43%) of 7 patients were admitted to the PICU. These findings suggest that patients with HF were more severely ill than patients who did not have HF and emphasize the importance of diagnosing HF in this high-risk population. In Israel, not all children with CHD are treated with an anti-RSV vaccine (palivizumab) because it is only partially funded by the ministry of
1512
N. Samuel et al. / American Journal of Emergency Medicine 32 (2014) 1510–1512
health. All the patients in our study were not previously treated with palivizumab. This finding emphasizes the importance of the immunization against RSV in children with CHD. This pilot study is the first report on BNP in children with CHD and RSV infection. Our findings suggest that, when a young child with CHD presents to the ED with RSV bronchiolitis, his BNP level can be used to ascertain the presence of HF. If a high BNP level is detected, a diagnosis of HF is suspected, and a more severe disease course is expected. This is particularly important when a cardiology consult is not readily available and referral to an increased level of care may be warranted. Our study has several limitations. First, the small sample size possibly prevented proportional representation of different etiologies of CHD in this heterogeneous population. Second, a cardiologist's evaluation for HF was not performed immediately after ED admission but 4 to 12 hours later. Third, although cardiologists were practically blinded to the BNP level because only the researchers were informed about the BNP level, there was no formal blinding mechanism in this study. Fourth, because no baseline measurements were compared, this study is not able to determine if the BNP is
useful to distinguish ongoing chronic HF that is stable vs worsening HF or new onset HF. 5. Conclusion The results of this small cohort suggest that the BNP test can be useful to ascertain the presence of HF in children with CHD who present to the ED with RSV bronchiolitis. References [1] Das BB. Plasma B-type natriuretic peptides in children with cardiovascular diseases. Pediatr Cardiol 2010;31:1135–45. [2] Law YM, Hoyer AW, Reller MD, et al. Accuracy of plasma B-type natriuretic peptide to diagnose significant cardiovascular diseases in children: the Better Not Pout Children! Study. J Am Coll Cardiol 2009;541:1467–75. [3] Macicek SM, Macias CG, Jefferies JL, et al. Acute heart failure syndromes in the pediatric emergency department. Pediatrics 2009;124:e898-e904. [4] Koulouri S, Acherman RJ, Wong PC, et al. Utility of B-type natriuretic peptide in differentiating congestive heart failure from lung disease in pediatric patients with respiratory distress. Pediatr Cardiol 2004;25:34–6. [5] Willson DF, Landrigan CP, Horn SD, et al. Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. J Pediatr 2003;143(50):142–9.
