Ann Thorac Surg 2004;77:164-167
© 2004 The Society of Thoracic Surgeons
Original article: cardiovascular
Plasma brain natriuretic peptide reflects left ventricular function during percutaneous cardiopulmonary support
Toshihiro Ohata, MDa*,
Tetsuo Sakakibara, MDa,
Hiroshi Takano, MDa,
Hironori Izutani, MDa
a Department of Cardiovascular Surgery, Osaka Police Hospital, Osaka, Japan
Accepted for publication June 25, 2003.
* Address reprint requests to Dr Ohata, Department of Cardiovascular Surgery, Kawachi General Hospital, 28 Yokomakura-Higashi, Higashi-Osaka 578-0955, Japan
e-mail: tohata{at}aol.com
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Abstract
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BACKGROUND: Plasma levels of brain natriuretic peptide (BNP), a cardiac hormone secreted predominantly from the ventricle, are elevated in patients with myocardial infarction, hypertension, and dilated cardiomyopathy. In this study, we assessed the usefulness of measuring BNP to evaluate left ventricular function in patients with severe heart failure receiving mechanical circulatory support.
METHODS: Plasma BNP and creatine kinase (CK)-MB levels were measured serially in 8 consecutive patients with cardiogenic shock who received percutaneous cardiopulmonary support (PCPS) at Osaka Police Hospital from August 1999 to March 2000. Coronary artery bypass grafting or percutaneous transluminal coronary angioplasty was also performed in 5 patients during PCPS; in addition, 1 patient underwent insertion of a left ventricular venting catheter and implantation of a left ventricular assist system after PCPS.
RESULTS: Five patients were weaned from PCPS, and 3 died. In survivors, plasma BNP and CK-MB levels correlated positively and significantly (r = 0.968, p = 0.03). After PCPS was initiated, plasma BNP levels gradually decreased in survivors, but not in patients who died (p = 0.003).
CONCLUSIONS: These results suggest that plasma BNP levels accurately reflect myocardial damage in patients undergoing PCPS. A decrease in BNP might appear to indicate improved left ventricular function and predict successful weaning from mechanical support.
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Introduction
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Brain natriuretic peptide (BNP), first isolated from the porcine brain, has a 17 amino-acid ring structure that is highly homologous with atrial natriuretic peptide (ANP) and forms a natriuretic peptide family with ANP and C-type natriuretic peptide [1]. Initial reports indicated that BNP is predominantly synthesized and secreted from the ventricle [2], and that plasma BNP levels increase in proportion to the severity of congestive heart failure [3]. Subsequent studies revealed increased plasma BNP levels in patients with myocardial infarction, hypertension, and dilated cardiomyopathy [4–6], and demonstrated that increased left ventricular end-systolic wall stress stimulates BNP synthesis and secretion in patients with aortic stenosis [7]. However, changes in plasma BNP have not been evaluated in patients with severe heart failure receiving mechanical circulatory support. In this study, we investigated the usefulness of measuring plasma BNP levels to evaluate left ventricular function during percutaneous cardiopulmonary support (PCPS) in patients with cardiogenic shock.
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Patients and methods
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Eight consecutive patients received PCPS for cardiogenic shock at Osaka Police Hospital from August 1999 to March 2000 (Tables 1 and 2). There were 6 men and 2 women, aged 29 to 76 years old (mean 61 ± 15 years). The diagnoses were acute myocardial infarction at left main trunk in 3 patients, anterior acute myocardial infarction, unstable angina, left ventricular rupture, myocarditis, and dilated cardiomyopathy. Coronary artery bypass grafting or percutaneous transluminal coronary angioplasty were performed during PCPS in 5 patients; in one additional a left ventricular venting catheter was inserted and a left ventricular assist system was subsequently implanted.
PCPS system
The PCPS system consisted of a hollow-fiber microporous membrane oxygenator (Menox AL6000; Dainippon Ink & Chemicals Inc., Tokyo, Japan), a heat exchanger, a centrifugal pump (Sarns centrifugal pump; Terumo Cardiovascular Systems, Ann Arbor, MI), arterial and venous cannulas, and standard 3/8-inch tubing. The blood contact surface of the circuit was heparin coated with Carmeda Bioactive Surface (Medtronic Cardiopulmonary Division, Anaheim, CA). PCPS was established with venous drainage from right atrium through right femoral vein and arterial blood returned through the femoral artery. A 17-Fr or 19-Fr venous cannula was inserted to achieve a pump flow more than 2.5 L · min-1 · m-2. After stable hemostasis was obtained, a minimal dose of heparin was intravenously administered to maintain activated clotting time between 200 and 250 seconds.
Measurements
Plasma levels of BNP were serially measured every 24 hours after the establishment of PCPS (Shionogi & Co, Ltd, Osaka, Japan). Creatine kinase (CK), creatine kinase-MB isozyme (CK-MB), aspartate aminotransferase, and lactate dehydrogenase were also serially examined. The informed consent to obtain the blood samples during the PCPS was obtained from the family of each patient.
Statistics
All values are expressed as the mean ± standard deviation of the mean. Comparisons between the groups over time were performed by two-way, repeated-measures analysis of variance (ANOVA), followed by Bonferroni's test. Differences were considered significant at p less than 0.05. Repeated-measures ANOVA was implemented with multiple linear measure regression and dummy variables to account for the interventions and differences between the patients. The regression model was
where y is the dependent variable of interest, and St, Di, and ai are the dummy variables. Di accounts for between-patient differences by allowing n = 3 patients to have different mean responses: Di = 1 for patient i (i 
n-1), -1 for patient n, and 0 otherwise; and ai represents the deviation from the overall mean value for patient i (i = 1,... n-1). All analyses were performed with Statview 4.5 statistical package (Abacus Concepts Inc, Berkeley, CA) and SIGMASTAT (Jandel Scientific, San Rafael, CA).
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Results
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The mean duration of PCPS was 3.6 ± 1.9 days (range 2.0 to 7.0 days). Five of 8 patients (62.5%) were weaned from PCPS. In 4 patients the centrifugal pump was exchanged twice each. Three patients could not be weaned from PCPS and died.
Brain natriuretic peptide
In all 5 patients who were weaned from PCPS, plasma BNP increased markedly after the cardiac-related event, decreased gradually after initiation of PCPS, and increased again after weaning. In all but 1 patient (patient 2), the BNP at weaning was lower than the initial BNP (Fig 1).
In the 3 patients who died, plasma BNP was elevated after the cardiac-related event and did not decrease during PCPS, except in 1 patient who suffered whole-brain cerebral infarction after heparin administration was stopped because of systemic bleeding (Fig 2).
The pattern of change of in BNP was significantly different between groups (p = 0.003).
CK-MB and relation to BNP
During the first 24 hours of PCPS, CK-MB levels decreased in survivors but exhibited no consistent pattern in patients who died.
In survivors, plasma BNP correlated significantly and positively with CK-MB levels (Fig 3).
Maximum cardiac enzyme levels
The maximum CK-MB level did not differ in survivors and patients who died (312 ± 232 and 365 ± 196 U/L, respectively; p = 0.78). Similarly, there was no difference in the maximum values of CK (5179 ± 6168 vs 13729 ± 12040 U/L, p = 0.27), aspartate aminotransferase (978 ± 1104 vs 895 ± 448 U/L, p = 0.91), and lactate dehydrogenase (2377 ± 1497 vs 3766 ± 1955 U/L, p = 0.33).
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Comment
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Enhanced myocardial BNP release has been demonstrated previously in patients with acute myocardial infarction [4], aortic valve stenosis [7], and ischemia-reperfusion after global ischemia associated with cardioplegic arrest [8]. In this study, we demonstrate that plasma BNP levels increased markedly in patients with cardiogenic shock undergoing PCPS. In patients who could be weaned from PCPS, the BNP levels gradually decreased, and plasma BNP correlated significantly and positively with CK-MB levels. These findings suggest that the pattern of change in BNP during PCPS might predict myocardial recovery from cardiac dysfunction. Since CK-MB is released from necrosed myocytes, and BNP is synthesized by viable myocytes, BNP levels may reflect with great exactitude both myocardial damage and the reaction of viable myocytes, and may be superior to CK-MB.
PCPS provides potent hemodynamic support [9]. It is convenient as an intraaortic balloon pump, but provides greater circulatory support and can be used to resuscitate patients from circulatory collapses, cardiac arrest, postcardiotomy cardiogenic shock, and impaired end-organ function of end-stage cardiac failure [10, 11]. However, we have had difficulty in evaluating cardiac function accurately during PCPS because echocardiography revealed only findings of cardiac stunning, and the patients were too sick to undergo cardiac scintigraphy. Therefore, a convenient method is needed to evaluate cardiac function in patients receiving mechanical support.
Despite improvement in PCPS devices and their use [12], the clinical results are not yet satisfactory. Patients with critical cardiogenic shock or advanced multiple organ failure require additional surgical intervention and advanced circulatory support, such as a biventricular assist device and heart transplantation [13]. To improve clinical outcome it will be necessary to prevent complications related to the maintenance of PCPS, and to develop better strategies for treatment after establishment of PCPS.
The validity of this study is limited by the small number of patients and the uncertainty about the relationship between the evaluation of global cardiac function (eg, as assessed by echocardiography and left ventriculography) and other mediators, such as human heart fatty acid binding protein [14]. Some studies have suggested that inflammatory mediators (such as tumor necrosis factor-
) norepinephrine might indicate cardiac damage and recovery [15]. However, we did not measure these values in our patients. Further investigation is required to establish an accurate and reliable marker of cardiac function during assisted mechanical circulation.
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References
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Top
Abstract
Introduction
), plasma BNP decreased markedly after the initiation of PCPS. • = patient 1; 
= patient 2; 
= patient 5. (BNP = brain natriuretic peptide; PCPS = percutaneous cardiopulmonary support; POD = postoperative day.)
= patient 7; • = patient 8. (BNP = brain natriuretic peptide; PCPS = percutaneous cardiopulmonary support; POD = postoperative day.)
= patient 3. (BNP = brain natriuretic peptide; CK-MB = creatine kinase-MB; PCPS = percutaneous cardiopulmonary support.)