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J Thorac Cardiovasc Surg 2008;135:746-753
© 2008 The American Association for Thoracic Surgery

Surgery for Congenital Heart Disease

Perioperative B-type natriuretic peptide levels predict outcome after bidirectional cavopulmonary anastomosis and total cavopulmonary connection

Jong-Hau Hsu, MDa,d, Peter E. Oishi, MDa, Roberta L. Keller, MDa, Omar Chikovani, MDa, Tom R. Karl, MDb, Anthony Azakie, MDb, Ian Adatia, MBChBa, Jeffrey R. Fineman, MDa,c,*

a Department of Pediatrics, University of California, San Francisco, Calif
b Department of Surgery, University of California, San Francisco, Calif
c Cardiovascular Research Institute, University of California, San Francisco, Calif
d Department of Pediatrics, Kaohsiung Medical University, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Received for publication August 30, 2007; revisions received October 5, 2007; accepted for publication October 31, 2007.

* Address for reprints: Jeffrey R. Fineman, MD, Department of Pediatrics, UCSF Medical Center, 513 Parnassus Avenue, Box 0106, San Francisco, CA 94143. (Email: jeff.fineman{at}ucsf.edu).


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
Objective: The objective of the study was to determine perioperative B-type natriuretic peptide levels in infants and children undergoing bidirectional cavopulmonary anastomosis or total cavopulmonary connection, and the predictive value of B-type natriuretic peptide levels for outcome.

Methods: Plasma B-type natriuretic peptide levels were measured before and 2, 12, and 24 hours after surgery in 36 consecutive patients undergoing bidirectional cavopulmonary anastomosis (n = 25) or total cavopulmonary connection (n = 11). B-type natriuretic peptide levels were evaluated as predictors of outcome.

Results: B-type natriuretic peptide levels increased after surgery, peaking at 12 hours in most patients. In the bidirectional cavopulmonary anastomosis group, patients with 12-hour B-type natriuretic peptide ≥ 500 pg/mL had a longer duration of mechanical ventilation (165 ± 149 hours vs 20 ± 9 hours, P = .004), longer intensive care unit stay (11 ± 7 days vs 4 ± 2 days, P = .001), and longer hospital stay (20 days ± 12 vs 9 days ± 5, P = .003). A 12-hour B-type natriuretic peptide ≥ 500 pg/mL had a sensitivity of 80% and a specificity of 80% for predicting an unplanned surgical or transcatheter cardiac intervention, including transplantation (P = .03). In the total cavopulmonary connection group, preoperative B-type natriuretic peptide levels were highest in patients with total cavopulmonary connection failure compared with patients with a good outcome (88 ± 46 pg/mL vs 15 ± 6 pg/mL, P = .03).

Conclusion: Postoperative B-type natriuretic peptide levels predict outcome after bidirectional cavopulmonary anastomosis, and preoperative levels are greater in patients with both early and late total cavopulmonary connection failure compared with patients with a good outcome.

Abbreviations and Acronyms BCPA = bidirectional cavopulmonary anastomosis; BNP = B-type natriuretic peptide; CPB = cardiopulmonary bypass; ICU = intensive care unit; LCOS = low cardiac output syndrome; mPAP = mean pulmonary artery pressure; PVR = pulmonary vascular resistance; Qp/Qs = ratio of pulmonary blood flow over systemic blood flow; SVC = superior vena cava; SVEDP = systemic ventricular end-diastolic pressure; TCPC = total cavopulmonary connection


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
Surgical palliation of univentricular cardiac defects usually requires a series of staged operations. Most often, the functionally single ventricle supplies blood in parallel to the systemic and pulmonary circulations after first-stage palliation. A bidirectional cavopulmonary anastomosis (BCPA) followed by a total cavopulmonary connection (TCPC) allows the transition of patients to a circulation in series, wherein the functionally single ventricle ejects blood to the systemic vasculature while passive venous return provides blood to the pulmonary vasculature. However, the absence of a dedicated subpulmonary ventricle requires the functionally single ventricle to supply the total kinetic energy for blood flow through both circulations, which renders patients sensitive to elevations in pulmonary vascular resistance (PVR), valvular dysfunction, or decreased ventricular performance.1-5Go Although mortality after BCPA and TCPC is low with careful patient selection, the ability to predict adverse postoperative outcomes is inadequate, and there remains an unpredictable risk of early and late TCPC takedown because of poor adaptation to the Fontan circulation.

B-type natriuretic peptide (BNP) is a 32-amino acid polypeptide hormone secreted by the myocardium in response to various stimuli that has natriuretic, diuretic, and vasoactive properties.6,7Go Recent studies found that BNP levels predicted postoperative morbidity and mortality after surgery for the repair or palliation of congenital cardiac defects.8-11Go However, these studies also demonstrated marked variability in absolute BNP levels, perioperative changes in BNP, and their specific predictive values, in part because of differences between the specific age groups and cardiac defects that were investigated.8-11Go Thus, although the available data demonstrate clinical utility for BNP as a biomarker in subsets of patients after congenital cardiac surgery, they do not directly establish a use in patients after BCPA or TCPC.

We hypothesized that perioperative BNP levels would predict unexpected outcomes after BCPA and TCPC in patients otherwise deemed to be suitable operative candidates on the basis of standard preoperative hemodynamic assessments. Therefore, the objectives of this study were (1) to determine perioperative BNP levels in infants and children undergoing BCPA or TCPC, and (2) to investigate the potential predictive value of BNP levels for postoperative outcome.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusions
 References
 
We conducted a prospective cohort study in the pediatric cardiac intensive care unit (ICU) at the University of California, San Francisco Children's Hospital between July of 2005 and July of 2006. Eligible patients were children aged less than 17 years with congenital cardiac defects who were undergoing BCPA or TCPC.

The preoperative anesthesia management, intraoperative surgical strategy, and subsequent pediatric cardiac ICU management followed standard institutional practices. The surgical and medical teams involved in the management of the patients were blinded to the BNP values.

We obtained written informed consent from the patients' parents or guardians before enrollment in the study. The University of California, San Francisco review board approved the study.

Data Collection
Blood samples were obtained from an arterial catheter just after induction of anesthesia, and at 2, 12, and 24 hours after surgery. For patients who could not be separated from cardiopulmonary bypass (CPB), only the preoperative specimen was obtained. The samples were placed immediately on ice in chilled ethylenediamine tetraacetic acid-treated tubes and centrifuged at 3000 rpm for 15 minutes at 4°C. Separated plasma was stored at –20°C. Within 4 days, the plasma was thawed to room temperature and BNP levels were measured using a commercially available fluorescence immunoassay (Triage Meter Plus, Biosite Diagnostic, San Diego, Calif). The measurable range of BNP on this device is between 5 and 5000 pg/mL. The estimated coefficient of variation for the assay is 9.2% to 11.4%.

Perioperative clinical and biochemical data were collected prospectively at each sampling point and daily thereafter by an observer blinded to the BNP data. The clinical data collected included the following: patient demographics; preoperative hemodynamic data obtained at the time of cardiac catheterization, including the ratio of pulmonary blood to systemic blood flow (Qp/Qs), PVR, mean pulmonary artery pressure (mPAP), cardiac index, and systemic ventricular end-diastolic pressure (SVEDP); CPB duration; and postoperative hemodynamic and clinical outcomes, including inotrope dose, mean systemic arterial pressure, common atrial pressure, heart rate, ICU and hospital length of stay after operation, urine output, fluid balance 24 hours after surgery, and duration of mechanical ventilation. Perioperative biochemical data collected included hematocrit, arterial and venous blood gases, serum lactate, blood urea nitrogen, and creatinine.

Outcome Measures
The primary end point was the occurrence of an adverse outcome within 1 year of surgery, defined as death or the need for an unplanned surgical or transcatheter cardiac intervention, including cardiac transplantation.

Secondary end points were the (1) duration of mechanical ventilation ≥ 48 hours postoperatively, (2) ICU length of stay, (3) hospital length of stay, and (4) development of low cardiac output syndrome (LCOS) within 48 hours after surgery. The definition of LCOS was derived from criteria published by Hoffman and colleagues,12Go which included a combination of changes in clinical signs and biochemical indicators. Criteria included tachycardia, oliguria, poor perfusion, cardiac arrest, or metabolic acidosis, and the need for interventions aimed at augmenting cardiac output, such as increased pharmacologic support relative to the baseline and cardiac pacing.

Calculations
Inotrope use was quantified by a score adapted from Wernovsky and colleagues.13Go The score was calculated from the level of inotropic support the patients were receiving (in micrograms/kilogram/minute) at each sampling point according to the following equation: Formula .

Data Analysis
Differences in the continuous variables between groups were tested with the Student t test or Mann–Whitney U test. Differences in the categoric variables between groups were tested with the Fisher exact test. Correlations between variables were performed by the Spearman rank correlation method. The utility of BNP as a prognostic indicator of postoperative outcome was evaluated using receiver operating characteristic curves. Changes in BNP levels over time were compared by repeated-measures analysis of variance. Statistical analyses were performed with Prism 4.0 (GraphPad Software, Inc, San Diego, Calif) and Stata 9.0 (Stata Corp, College Station, Tex).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusions
 References
 
Subjects
Thirty-six consecutive patients were enrolled in the study. Twenty-five patients underwent BCPA, and 11 patients underwent TCPC. Of the 25 patients in the BCPA group, 1 patient underwent a hemi-Fontan procedure, 2 patients had bilateral superior venae cavae (SVC) with bilateral BCPA, and the remainder underwent BCPA of a single SVC. All 11 patients in the TCPC group had an extracardiac conduit placed between the inferior vena cava and the pulmonary artery, 4 of which were fenestrated.

All patients had a cardiac catheterization performed within 2 months before surgery. CPB was used in 32 patients (89%). One patient could not be separated from CPB after TCPC until the TCPC was taken down. Only the preoperative BNP value was included in the analysis for this patient.

The patients' preoperative characteristics are shown in Go Table 1. The younger patients undergoing BCPA had faster heart rates, lower mean arterial pressure, higher mPAP, and larger Qp/Qs ratios than those undergoing TCPC.


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  		Table 1 Preoperative characteristics
 
Outcomes
Primary end points
Seven patients (19%) had an adverse outcome, 5 of 25 patients in the BCPA group and 2 of 11 patients in the TCPC group. The preoperative diagnoses and specific postoperative events classifying the adverse outcomes are shown in Go Table 2. No enrolled patient died during the study period.


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  		Table 2 Diagnoses and specific postoperative events of patients with an adverse outcome
 
The demographic characteristics; degree of atrioventricular valve regurgitation; pre- and postoperative hemodynamic indices; and postoperative creatinine, lactate, and inotrope scores did not differ between patients undergoing BCPA with and without an adverse outcome. Additional surgery at the time of BCPA was required in 14 patients, including pulmonary artery plasty, aortoplasty, atrial reduction, and atrioventricular valve repair. The percentage of patients requiring additional surgery did not differ between patients with and without adverse postoperative outcome (55% vs 60%).

Preoperative hemodynamics fulfilled institutional criteria for all patients undergoing a TCPC, including the 2 patients with an adverse outcome. Of these 2 patients, 1 had Ebstein's anomaly with a hypoplastic right ventricle and total anomalous pulmonary venous return that had been previously corrected at the time of BCPA. This patient also underwent atrial reduction at the time of TCPC. The second patient had an unbalanced atrioventricular septal defect with right atrial isomerism and anomalous right and middle hepatic veins. This patient underwent unifocalization of the right and middle hepatic veins at the time of TCPC. No patient with a good outcome after TCPC required additional surgery.

Circulatory arrest was used during the operation for 2 patients undergoing BCPA, neither of whom had an adverse postoperative outcome. No patient in the TCPC group underwent circulatory arrest.

Secondary end points
Eight patients (22%) required mechanical ventilation ≥ 48 hours postoperatively, 7 of 25 patients in the BCPA group and 1 of 11 patients in TCPC group. The median duration of mechanical ventilation was 22 hours (range: 8–373 hours) in patients who underwent BCPA and 14 hours (range: 8–168 hours) in patients who underwent TCPC. Seven patients (19%) developed LCOS within the first 48 hours after surgery, 4 of 25 patients in the BCPA group and 3 of 11 patients in TCPC group. The ICU stay and hospital stay were 6 ± 5 days and 13 ± 9 days in the BCPA group, respectively, and 6 ± 2 days and 18 ± 10 days in the TCPC group, respectively.

Perioperative BNP Levels
Perioperative BNP levels are shown in Go Table 3. BNP levels increased after surgery in all patients, with peak levels at 12 hours in 23 patients (66%) and at 24 hours in 8 patients (23%). BNP levels were greater preoperatively and at 2 and 12 hours postoperatively in the BCPA group than in the TCPC group (Table 3).


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  		Table 3 Perioperative B-type natriuretic peptide levels
 
Preoperative BNP Levels and Outcome
BCPA group
Preoperative BNP levels were not different between patients with or without an adverse outcome, mechanical ventilation ≥ 48 hours, or LCOS, and there was no correlation between preoperative BNP levels and ICU or hospital stay.

Preoperative BNP levels correlated with 2-hour BNP levels (rho = 0.84, P < .001), but not with 12- and 24-hour BNP levels. There was no association between preoperative BNP levels and sex, and preoperative BNP levels did not correlate with preoperative weight, Qp/Qs, PVR, mPAP, cardiac index, SVEDP, mean arterial pressure, heart rate, arterial hemoglobin oxygen saturation, hematocrit, serum lactate, blood urea nitrogen, or creatinine.

TCPC group
Preoperative BNP levels were greater in patients with an adverse outcome than in patients with a good outcome (Go Figure 1). Preoperative BNP levels were not different between patients with or without mechanical ventilation ≥ 48 hours, or LCOS, and there was no correlation between preoperative BNP levels and ICU or hospital stay.


Figure 1
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  		Figure 1. Comparisons of preoperative BNP levels between patients with (n = 2) and without (n = 9) adverse outcome after TCPC. Horizontal lines = mean values. BNP, B-type natriuretic peptide; TCPC, total cavopulmonary connection.

 
Preoperative BNP levels correlated with 2-hour BNP levels (rho = 0.74, P = .03), but not with 12 and 24-hour BNP levels. There was no association between preoperative BNP levels and sex, and preoperative BNP levels did not correlate with preoperative weight, Qp/Qs, PVR, mPAP, cardiac index, SVEDP, mean arterial pressure, heart rate, arterial oxygen saturation, hematocrit, serum lactate, urea, or creatinine.

Postoperative BNP Levels and Outcome
BCPA group
BNP levels at 12 and 24 hours were greater in patients with an adverse outcome than in patients with a good outcome (Go Figure 2). BNP levels at all postoperative time points were greater in patients requiring mechanical ventilation ≥ 48 hours (n = 7) than in patients requiring mechanical ventilation < 48 hours (n = 18, P < .05). In addition, BNP levels at 2, 12, and 24 hours correlated with the duration of mechanical ventilation (rho = 0.44, P = .02; rho = 0.41, P = .04; rho = 0.45, P = .02, respectively). BNP levels at 12 hours were greater in patients who developed LCOS within 48 hours after surgery than in patients who did not (913 ± 693 pg/mL vs 308 ± 299 pg/mL, P = .04). BNP levels at 2 hours correlated with ICU stay (rho = 0.47, P = .01), and BNP levels at 2, 12, and 24 hours correlated with hospital stay (rho = 0.56, P = .003; rho = 0.40, P = .04; rho = 0.39, P = .04, respectively).


Figure 2
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  		Figure 2. Comparison of perioperative BNP levels between patients with adverse or good outcome after BCPA. BNP levels at 12 and 24 hours are greater in patients with adverse outcome (n = 5) than in patients with good outcome (n = 20). There was a significant interaction between outcome and sample time (P < .01). Data are presented as mean ± standard error. (* P < .05 and ** P < .01 vs good outcome.) BNP, B-type natriuretic peptide; BCPA, bidirectional cavopulmonary anastomosis.

 
There were no correlations between postoperative BNP levels and mean arterial pressure, common atrial pressure, arterial oxygen saturation, hematocrit, urea, creatinine, or duration of CPB.

Receiver operating characteristic curves were used to evaluate various cutoff values of 12-hour BNP to predict an adverse outcome and mechanical ventilation ≥ 48 hours. A 12-hour BNP cutoff value of ≥ 500 pg/mL had a sensitivity of 80% and a specificity of 80% for predicting an adverse outcome (area under the curve: 0.81, P = .03). A 12-hour BNP cutoff value of ≥ 500 pg/mL had a sensitivity of 86% and a specificity of 89% for predicting mechanical ventilation ≥ 48 hours (area under the curve: 0.82, P = .01).

Because a 12-hour BNP level ≥ 500 pg/mL predicted both an adverse outcome and mechanical ventilation ≥ 48 hours, we dichotomized patients by BNP levels of < 500 pg/mL or ≥ 500 pg/mL. The characteristics of patients with a 12-hour BNP level < 500 pg/mL and ≥ 500 pg/mL are shown in Go Table 4. Patients with a 12-hour BNP level ≥ 500 pg/mL had a greater incidence of LCOS and a longer ICU and hospital stay than patients with a 12-hour BNP level < 500 pg/mL (Table 4).


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  		Table 4 Characteristics of patients undergoing bidirectional cavopulmonary anastomosis with a 12-hour B-type natriuretic peptide level < or ≥ 500 pg/mL
 
TCPC group
Postoperative BNP levels were not different between patients with or without an adverse outcome, mechanical ventilation ≥ 48 hours, or LCOS, and there was no correlation between postoperative BNP levels and length of ICU or hospital stay.

Other Variables and Outcome
Age and preoperative hemodynamic data obtained from cardiac catheterizations were not associated with any primary or secondary outcomes. We examined further the relationship between serum lactate and outcome. We found that 24-hour lactate levels were correlated with the duration of mechanical ventilation (rho = 0.52, P = .01). In addition, 24-hour lactate levels were greater in patients who required mechanical ventilation ≥ 48 hours than in patients who did not (1.3 ± 0.4 mmol/L vs 0.8 ± 0.2 mmol/L; P = .01). However, the mean lactate values in both groups were within the normal range for our laboratory.


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusions
 References
 
These data indicate that BNP levels predict outcome after BCPA and suggest a potential prognostic role for BNP before TCPC. Although lactate levels at 24 hours were correlated with the duration of mechanical ventilation, no other hemodynamic or biochemical data were associated with postoperative outcome. Previously identified risk factors for patients undergoing BCPA include atrioventricular valve regurgitation, elevated pulmonary artery pressure, a systemic right ventricle, anomalous pulmonary venous drainage, tricuspid valvuloplasty, elevated SVEDP, bilateral SVC, unbalanced atrioventricular septal defect, and heterotaxy syndrome.1,3,14Go Although the present study was not designed primarily to evaluate individual risk factors for outcome after BCPA, we did not find an association between these factors and outcome, making BNP levels uniquely predictive of outcome after BCPA in this study.

Of the 11 patients undergoing TCPC in our study, 2 patients required takedown to a BCPA. Preoperative BNP levels were greatest in these patients. General criteria of suitability for TCPC have been described and include normal systemic venous return, mPAP less than 15 mm Hg, low PVR, good ventricular function, a competent atrioventricular valve, and the absence of pulmonary artery distortion.5Go With the exception of 1 patient with a good outcome who had a preoperative mPAP greater than 15 mm Hg (but also an elevated left atrial pressure and a normal calculated PVR), all of the patients met these criteria. These findings suggest that preoperative BNP levels may provide valuable supplemental data to aid in decisions regarding the timing or advisability of a TCPC.

We found that BNP levels increased after BCPA and TCPC. This finding is in contrast with a study by Sun and colleagues15Go that found no change in BNP levels after BCPA or Fontan. Because preoperative, but not postoperative, BNP levels were greater in their cohort than ours, the inconsistency between groups may be explained by differences in preoperative hemodynamics. In a study of 9 patients that included 4 patients after TCPC, Ationu and colleagues16Go reported decreases in BNP after surgery. However, in a larger study of 30 patients after TCPC, Yoshimura and colleagues17Go found that BNP levels increased postoperatively in a manner similar to patients in our study. Furthermore, in a study of 25 patients that included 5 patients with BCPA and 5 patients with TCPC, Costello and colleagues18Go found that BNP levels increased after surgery in both groups and correlated with CPB time. A relationship between perioperative BNP levels and outcome was not found in any of these prior studies, and thus the present study is the first to suggest a prognostic role for BNP in this patient population.

The regulation of BNP production and release in health and disease remains incompletely understood. However, in vivo and in vitro investigations demonstrate that ventricular volume and pressure loading increase BNP expression.19-21Go In addition, several stimuli relevant to patients undergoing cardiac surgery, including catecholamines, endothelin-1, and cytokines, have been demonstrated to increase BNP expression.21,22Go Last, several additional factors with particular importance for patients with single ventricle physiology have been correlated with BNP levels, including hypoxia and the Qp/Qs ratio.23,24Go In the present study, preoperative BNP levels were greater in patients before BCPA than TCPC. This result is consistent with several previous studies, but not all.18,25-28Go However, our findings are in keeping with increased volume and pressure loading after stage 1 palliation, reflected by higher mPAP and larger Qp/Qs ratios in patients before BCPA compared with patients before TCPC.

The mechanisms underlying the greater increase in BNP in patients with an adverse outcome are likely variable, but speculative. Three patients with an adverse outcome had residual defects that resulted in increased SVC pressure and decreased pulmonary blood flow. A recent study by Law and colleagues25Go of patients with cavopulmonary connections found that BNP levels increased with ventricular failure but not with isolated cavopulmonary failure, defined as systemic venous congestion without evidence of ventricular dysfunction. The study of Law and colleagues included mostly an outpatient population, whereas the present study focused on the immediate perioperative period. In addition, because patients with an adverse outcome in our study also had an increased incidence of LCOS, it is possible that the patients with residual anatomic defects of the cavopulmonary circuit also had ventricular dysfunction or an elevated afterload. One patient with an adverse outcome in the BCPA group required transcatheter aortic dilation for residual aortic arch obstruction. The elevation in BNP in this patient is consistent with previous reports after relief of left ventricular outflow tract obstruction.29Go Finally, the mechanisms responsible for an elevation in preoperative BNP in patients with an adverse outcome after TCPC are unclear, particularly given that the preoperative hemodynamics were not different from patients with good outcome. We speculate that because BNP is a cardiac hormone, it may reflect myocardial dynamics in a unique manner that is more sensitive than current diagnostic methods.

We chose the duration of mechanical ventilation as a secondary end point because it is a common surrogate marker of disease severity that has been correlated to BNP levels in previous studies of patients after congenital cardiac surgery.8-10Go Given the potential deleterious effects of positive pressure ventilation and salutary effects of spontaneous respiration for patients with superior or complete cavopulmonary connections, our institutional practice is to separate patients from mechanical ventilation as early in their postoperative course as possible. Indeed, mechanical ventilation beyond 48 hours, the specific end point used in our study, is unusual, and thus represents an unexpected clinical outcome. It must be noted that there are no validated criteria for the discontinuation of mechanical ventilation for patients after BCPA or TCPC, and thus the decision to separate a patient from the ventilator was made on an individual basis by the attending physicians, who were blinded to the BNP values.

In addition, we used the development of LCOS as a secondary outcome, because it has been used as an end point in therapeutic trials in pediatric patients after cardiac surgery.12Go However, the majority of patients with LCOS developed it early in the postoperative course, before the 12-hour time point. Thus, postoperative BNP levels did not predict LCOS, but rather were associated with it. Whether therapies initiated in response to elevated BNP levels in the postoperative period could decrease the incidence of LCOS was not evaluated, but this warrants further study.

A limitation of this study is the sample size. Only 2 patients had a poor outcome after TCPC. However, because BNP was the only predictor of outcome, we suggest that it was an important finding and at least warrants a larger prospective study that would permit multivariate analysis.


   Conclusions
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
References
 
We found that postoperative BNP levels predict important outcomes after BCPA and that a cutoff of 500 pg/mL 12 hours after surgery was a sensitive and specific predictor of an unplanned cardiac intervention and mechanical ventilation beyond 48 hours. In addition, we found that preoperative BNP levels were greater in patients with early or late takedown of the TCPC than in those with a successful operation. Additional studies are warranted to define further the role of BNP in the management of these patients, but our study suggests that elevated BNP levels after BCPA should prompt a careful evaluation of hemodynamics and ventricular function, an investigation of the surgical accuracy of the anastomosis, and a search for additional anatomic defects. We suggest that BNP levels may be useful in the preoperative evaluation of patients considered for a TCPC.


   Acknowledgments
 
The authors thank nurse practitioners Megan Tracey, Julie Bushnell, and Laura Presnell, the pediatric critical care fellows, the cardiac intensive care nurses, the Pediatric Clinical Research Center, Adam Gorham, and Leslie Kurkjian for their invaluable assistance with the study.


   Footnotes
 
This research was supported in part by grants K08 HL086513 (P.E.O.), K23 HL079922 (R.L.K.), HL61284 (J.R.F.), and UL RR024131-01 from the National Center for Research Resources, all from the National Institutes of Health, and from the Foundation Leducq (J.R.F.) and Biosite Diagnostic (J.R.F.). J.H.H. was supported in part by the Department of Pediatrics, Kaohsiung Medical University Hospital, Taiwan.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 References
 

  1. Scheurer MA, Hill EG, Vasuki N, Maurer S, Graham EM, Bandisode V, et al. Survival after bidirectional cavopulmonary anastomosis: analysis of preoperative risk factors. J Thorac Cardiovasc Surg 2007;134:82-8989.e1-2.[Abstract/Free Full Text]
  2. Mahle WT, Cohen MS, Spray TL, Rychik J. Atrioventricular valve regurgitation in patients with single ventricle: impact of the bidirectional cavopulmonary anastomosis. Ann Thorac Surg 2001;72:831-835.[Abstract/Free Full Text]
  3. Alejos JC, Williams RG, Jarmakani JM, Galindo AJ, Isabel-Jones JB, Drinkwater D, et al. Factors influencing survival in patients undergoing the bidirectional Glenn anastomosis. Am J Cardiol 1995;75:1048-1050.[Medline]
  4. Gentles TL, Mayer Jr. JE, Gauvreau K, Newburger JW, Lock JE, Kupferschmid JP, et al. Fontan operation in five hundred consecutive patients: factors influencing early and late outcome. J Thorac Cardiovasc Surg 1997;114:376-391.[Abstract/Free Full Text]
  5. Hosein RB, Clarke AJ, McGuirk SP, Griselli M, Stumper O, De Giovanni JV, et al. Factors influencing early and late outcome following the Fontan procedure in the current era. The ‘Two Commandments’?. Eur J Cardiothorac Surg 2007;31:344-353.[Abstract/Free Full Text]
  6. Sudoh T, Kangawa K, Minamino N, Matsuo H. A new natriuretic peptide in porcine brain. Nature 1988;332:78-81.[Medline]
  7. Levin ER, Gardner DG, Samson WK. Natriuretic peptides. N Engl J Med 1998;339:321-328.[Medline]
  8. Hsu J, Keller R, Chikovani O, Cheng H, Hollander S, Karl T, et al. B-type natriuretic peptide levels predict outcome after neonatal cardiac surgery. J Thorac Cardiovasc Surg 2007;134:939-945.[Abstract/Free Full Text]
  9. Cannesson M, Bionda C, Gostoli B, Raisky O, di Filippo S, Bompard D, et al. Time course and prognostic value of plasma B-type natriuretic peptide concentration in neonates undergoing the arterial switch operation. Anesth Analg 2007;104:1059-1065tables of contents.[Abstract/Free Full Text]
  10. Shih CY, Sapru A, Oishi P, Azakie A, Karl TR, Harmon C, et al. Alterations in plasma B-type natriuretic peptide levels after repair of congenital heart defects: a potential perioperative marker. J Thorac Cardiovasc Surg 2006;131:632-638.[Abstract/Free Full Text]
  11. Chikovani O, Hsu J, Keller R, Karl T, Azakie A, Adatia I, et al. B-type natriuretic peptide levels predict outcomes for children on extracorporeal life support after cardiac surgery. J Thorac Cardiovasc Surg 2007;134:1179-1187.[Abstract/Free Full Text]
  12. Hoffman TM, Wernovsky G, Atz AM, Kulik TJ, Nelson DP, Chang AC, et al. Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation 2003;107:996-1002.[Abstract/Free Full Text]
  13. Wernovsky G, Wypij D, Jonas RA, Mayer Jr. JE, Hanley FL, Hickey PR, et al. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 1995;92:2226-2235.[Abstract/Free Full Text]
  14. Day RW, Orsmond GS, Sturtevant JE, Hawkins JA, Doty DB, McGough EC. Early and intermediate results of the Fontan procedure at moderately high altitude. Ann Thorac Surg 1994;57:170-176.[Abstract/Free Full Text]
  15. Sun LS, Dominguez C, Mallavaram NA, Quaegebeur JM. Dysfunction of atrial and B-type natriuretic peptides in congenital univentricular defects. J Thorac Cardiovasc Surg 2005;129:1104-1110.[Abstract/Free Full Text]
  16. Ationu A, Singer DR, Smith A, Elliott M, Burch M, Carter ND. Studies of cardiopulmonary bypass in children: implications for the regulation of brain natriuretic peptide. Cardiovasc Res 1993;27:1538-1541.[Abstract/Free Full Text]
  17. Yoshimura N, Yamaguchi M, Oshima Y, Oka S, Ootaki Y, Hasegawa T, et al. Suppression of the secretion of atrial and brain natriuretic peptide after total cavopulmonary connection. J Thorac Cardiovasc Surg 2000;120:764-769.[Abstract/Free Full Text]
  18. Costello JM, Backer CL, Checchia PA, Mavroudis C, Seipelt RG, Goodman DM. Effect of cardiopulmonary bypass and surgical intervention on the natriuretic hormone system in children. J Thorac Cardiovasc Surg 2005;130:822-829.[Abstract/Free Full Text]
  19. Zhang Y, Carreras D, de Bold AJ. Discoordinate re-expression of cardiac fetal genes in N(omega)-nitro-L-arginine methyl ester (L-NAME) hypertension. Cardiovasc Res 2003;57:158-167.[Abstract/Free Full Text]
  20. Schaub MC, Hefti MA, Harder BA, Eppenberger HM. Various hypertrophic stimuli induce distinct phenotypes in cardiomyocytes. J Mol Med 1997;75:901-920.[Medline]
  21. Hama N, Itoh H, Shirakami G, Nakagawa O, Suga S, Ogawa Y, et al. Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction. Circulation 1995;92:1558-1564.[Abstract/Free Full Text]
  22. Ma KK, Ogawa T, de Bold AJ. Selective upregulation of cardiac brain natriuretic peptide at the transcriptional and translational levels by pro-inflammatory cytokines and by conditioned medium derived from mixed lymphocyte reactions via p38 MAP kinase. J Mol Cell Cardiol 2004;36:505-513.[Medline]
  23. Hopkins WE, Chen Z, Fukagawa NK, Hall C, Knot HJ, LeWinter MM. Increased atrial and brain natriuretic peptides in adults with cyanotic congenital heart disease: enhanced understanding of the relationship between hypoxia and natriuretic peptide secretion. Circulation 2004;109:2872-2877.[Abstract/Free Full Text]
  24. Suda K, Matsumura M, Matsumoto M. Clinical implication of plasma natriuretic peptides in children with ventricular septal defect. Pediatr Int 2003;45:249-254.[Medline]
  25. Law YM, Ettedgui J, Beerman L, Maisel A, Tofovic S. Comparison of plasma B-type natriuretic peptide levels in single ventricle patients with systemic ventricle heart failure versus isolated cavopulmonary failure. Am J Cardiol 2006;98:520-524.[Medline]
  26. Koch A, Zink S, Singer H. B-type natriuretic peptide in paediatric patients with congenital heart disease. Eur Heart J 2006;27:861-866.[Abstract/Free Full Text]
  27. Hjortdal VE, Stenbog EV, Ravn HB, Emmertsen K, Jensen KT, Pedersen EB, et al. Neurohormonal activation late after cavopulmonary connection. Heart 2000;83:439-443.[Abstract/Free Full Text]
  28. Wahlander H, Westerlind A, Lindstedt G, Lundberg PA, Holmgren D. Increased levels of brain and atrial natriuretic peptides after the first palliative operation, but not after a bidirectional glenn anastomosis, in children with functionally univentricular hearts. Cardiol Young 2003;13:268-274.[Medline]
  29. Cowley CG, Bradley JD, Shaddy RE. B-type natriuretic peptide levels in congenital heart disease. Pediatr Cardiol 2004;25:336-340.[Medline]



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