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Is measurement of plasma brain natriuretic peptide levels a useful test to detect for surgical timing of valve disease?
International Journal of Cardiology 96 (2004) 21 – 24 www.elsevier.com/locate/ijcard
Is measurement of plasma brain natriuretic peptide levels a useful test to detect for surgical timing of valve disease? Masazumi Watanabe *, Mikiko Murakami, Hitoshi Furukawa, Hideki Nakahara Department of Cardiovascular Surgery, Tokyo Metropolitan Hiroo General Hospital, 2-34-10 Ebisu, Shibuya-ku, Tokyo 150-0013, Japan Received 25 December 2002; received in revised form 23 June 2003; accepted 25 July 2003
Abstract Background: The optimal timing of valve surgery is very important. In patients who are severely symptomatic, the marked improvement in symptomatic status observed following successful valve surgery. However, in patients with no or only mild symptoms, the decision is more difficult. The aim of this retrospective study was to determine whether the measurement of plasma brain natriuretic peptides (BNP) levels is useful to decide surgical timing for valve disease. Methods: Fifty-one patients with valve disease underwent single valve surgery (mitral stenosis, MS, 13; mitral regurgitation, MR, 16; aortic stenosis, AS, 14; aortic regurgitation, AR, 8 patients). Blood samples, echocardiographic and cardiac catheterization data were obtained before operation and echocardiographic examination were performed after 1-year of operations. Results: In patients subjected to single heart valve surgery, plasma BNP mean levels were 214.6 F 48.5 pg/ml. In plasma BNP levels, there was only significant difference between MS and AS group (MS 67.5 F 9.7 vs. AS 314.3 F 112.0 pg/ml, P = 0.04). There were no relationships between plasma BNP levels and pre-operative cardiac functions. After 1-year of the valve surgery, NYHA functional class was reduced in 36 patients (70.6%) and plasma BNP levels before the surgery significantly correlated with post-operative NYHA functional class. Conclusions: In this retrospective study, patients with high plasma BNP levels significantly impaired the improvement of clinical symptoms after surgery. We have suggested that plasma BNP levels is useful for detecting asymptomatic valvular disease, and is a clinical marker useful in determining the optimal surgical timing. D 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: BNP; Valve disease; Surgical timing; NYHA; Cardiac function
1. Introduction The optimal timing of valve surgery is very important. Performance of operation ‘‘too late’’ may result in the development of severe, irreversible left ventricular dysfunction, which may fail to improve or actually worsen following valve surgery; the outcome may be one of increased operative mortality, impaired long-term survival, and severe congestive heart failure in operative survivors. Conversely, performance of early valve surgery, before it is clearly necessary, places the patient at unnecessary risk of the many complications of the operation. Brain natriuretic peptide (BNP), a family of peptides with structural and biologic homologies to previously identified atrial natriuretic peptide (ANP), has been found in human cardiac tissue and plasma
* Corresponding author. Tel.: +81-33-444-1181; fax: +81-33-444-3196. E-mail address: [email protected] (M. Watanabe). 0167-5273/$ - see front matter D 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2003.07.009
[1]. In humans, BNP is expressed predominantly in the ventricles of failing hearts [2]. Recent studies [3,4] have demonstrated that the plasma BNP levels reflect left ventricular pressure and correlates to disease severity and prognosis. Evaluating of operative timing for valvular heart disease is a complex process because of the variety of valves available and the multiple number of valve-related events including left ventricular conditions that must be considered. The purpose of this study was to assess whether the measurement of plasma BNP levels is a useful test to detect for surgical timing of valve disease.
2. Patients and methods The study was approved by the institutional review board, and written informed consent was obtained from all patients. Subjects included 51 patients (28 males, 23 females) undergoing single valve surgery for heart valve disease
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M. Watanabe et al. / International Journal of Cardiology 96 (2004) 21–24
Table 1 Patients’ characteristics
AR, aortic regurgitation (n = 8); AS, aortic stenosis (n = 14); MR, mitral regurgitation (n = 16); MS, mitral stenosis (n = 13); Paw, pulmonary wedge pressure; LVEDP, left ventricular endo-diastolic pressure; LVDd, left ventricular diastolic dimension; LVM, left ventricular mass; LV mass volume was calculated with the following formula: 0.8[1.05{(LV end-diastolic dimension + ventricular septum + LV posterior wall)3 (LV end-diastolic dimension)3}] + 0.06). *, P = 0.04; **, P = 0.03; $, P = 0.02; #, P = 0.009; ##, P = 0.0006.
(mitral stenosis, MS, MVA = 1.0 F 0.3 cm2, 13 patients; mitral regurgitation, MR, moderate 6, severe 10, 16 patients; aortic stenosis, AS, max PG = 82 F 10.8 mmHg, 14 patients; aortic regurgitation, AR, moderate 3, severe 5, 8 patients). The mean F standard error (S.E.) age at valve surgery was 61.0 F 1.7 years (range: 17 – 82 years). All 51 patients were examined by echocardiography before the operation and after 1-year of the operation. Blood samples obtained before operation was assayed for plasma BNP levels. Plasma BNP levels were measured with a specific immunoradiometric assay for human BNP (Shiono ANP kit and Shiono BNP kit, Shionogi Co.) Follow-up consisted of echocardiography examinations after 1-year of surgery.
3. Statistical analyses Statistical analysis was performed using a PC computer with Statview IV statistical software (Abacus Concepts, Berkeley, CA). All values are expressed as mean F S.E. Data were analyzed using repeated measures analysis of variance and Dunnett’s t-test where appropriate. P values less than 0.05 were considered statistically significant. Regression analysis was performed with the least-square method and a case-wise deletion of missing data.
4. Results There were no deaths and all patients are alive and well. In patients subjected to single heart valve surgery, plasma BNP mean levels were 214.6 F 48.5 pg/ml (plasma BNP levels in normal healthy people offered by Mitsubishi Kagaku Bio-Clinical Laboratories, Inc.; BNP < 18.4 pg/ ml). The clinical characteristics of the study patients are listed in Table 1. There were no correlations between plasma BNP levels and echocardiographic parameters, cath data (LVDd: r 2 = 0.005, wall thickness: r 2 = 0.107, ejection fraction: r 2 = 0.012, LV mass: r 2 = 0.025). The mean F S.E. disease period (pointed out valvular lesion) was 6.1 F 1.0 year. No relationship existed between plasma BNP levels and disease period (r 2 = 0.075; AR: r 2 = 0.322, AS: r 2 = 0.198, MR: r 2 = 0.064, MS: r 2 = 0.023). In plasma BNP levels, there was only significant difference between MS and AS group. Thirty-one patients were classified in New York Heart Association (NYHA) functional class II (41.2%) or I (19.6%), 20 in class IV (11.8%) or III (27.5%) before surgery. There were no relationships between plasma BNP levels and pre-operative cardiac functions (Table 2).
Table 2 Correlation between cardiac function and plasma BNP levels Group
AR AS MR MS
Cardiac catheter data
Echocardiographic data
Paw
LVEDP
LVDd
EF
LVM
0.407 0.043 0.484 0.099
0.003 0.062 0.004 0.018
0.061 0.283 0.024 0.025
0.003 0.054 0.060 0.075
2
r = 0.212 0.125 0.320 0.146
Paw, pulmonary wedge pressure; LVEDP, left ventricular endo-diastolic pressure; LVDd, left ventricular diastolic dimension; LVM, left ventricular mass; LV mass volume was calculated with the following formula: 0.8[1.05{(LV end-diastolic dimension + ventricular septum + LV posterior wall)3 (LV end-diastolic dimension)3}] + 0.06).
Fig. 1. This graph shows the relationship between NYHA and plasma BNP levels before surgery. There were significant differences in plasma BNP levels among groups (NYHA I vs. III and IV, P = 0.04; NYHA II vs. IV, P = 0.001; NYHA III vs. IV, P = 0.001).
M. Watanabe et al. / International Journal of Cardiology 96 (2004) 21–24
Fig. 2. This graph shows the relationship between NYHA after surgery and plasma BNP levels. There were significant differences in plasma BNP levels among groups (NYHA I vs. III, P < 0.0001; NYHA II vs. III, P = 0.0001; NYHA I vs. II, P = 0.049).
However, in NYHA IV and III, plasma BNP levels were significantly higher than NYHA II and I (NYHA I: 56.5 F 17.1, II: 105.6 F 15.9, III: 412.6 F 136.4, IV: 397.8 F 201.7 pg/ml, Fig. 1). With respect to cardiac functional data, there were no significant differences in NYHA functional class. After 1-year of the valve surgery, NYHA functional class was reduced in 36 patients (70.6%), unchanged in 14 patients (27.5%) and getting worth in one patient (to class II from class I). NYHA functional class after surgery was not correlated with post-operative left ventricular ejection fraction (NYHA I: 64.8 F 3.3, NYHA II: 62.9 F 3.3, NYHA III: 60.8 F 7.1%). In retrospective analysis, there were no significant differences in pre-operative paw pressure, left ventricular end-diastolic pressure, left ventricular ejection fraction and left ventricular mass between postoperative NYHA III and I. However, plasma BNP levels before surgery significantly correlated with post-operative NYHA functional class (NYHA I: 89.2 F 12.8, II: 157.0 F 68.3, III: 1025.3 F 204.4 pg/ml, Fig. 2).
5. Discussion People with valvular heart disease are living longer, with less morbidity, than ever before. Valvular heart disease may first be diagnosed in the setting of an acute medical event, such as heart failure. The diagnosis of valvular heart disease is initially suspected before the onset of overt symptoms on the basis of the physical examination finding. Advances in surgical techniques and a better understanding of timing for surgical intervention account for increased rates of survival. Performance of operation ‘‘too late’’ inevitably causes left ventricular damage, eventually resulting in death. In this sense, the left ventricle is the ‘‘end
23
organ’’ damaged by underlying valvular disease. It is clear that some patients with mild or moderate valve lesions require surgery even though they are entirely asymptomatic. Our results also suggest that early surgery lead to good prognosis. However, in patients with no or only mild symptoms, the decision of surgery is more difficult. These different lesions such as stenosis and regurgitation result in different loading conditions, different pathophysiologies, and have different means for surgical correction. Therefore, it is thought that an indicator, which decides surgical timing, is required. In previous reports, measurement of plasma BNP levels was a useful test to detect for significant valve disease, LVH, and LV diastolic dysfunction [5,6]. Especially, plasma BNP levels could predict diastolic abnormalities in patients with normal systolic function [7]. We, in this retrospective study, examined whether plasma BNP levels is a useful marker to decide surgical timing for valve disease. Our results showed that patients with valve disease increased plasma BNP levels independent of cardiac catheterization data. In the present study, there was also no significant difference in plasma BNP levels between patients with left ventricular dysfunction (EF < 50%, n = 8) and normal function (>50%, n = 43) (EF < 50%:>50% = 181.6 F 49.0:391.8 F 155.3, P = 0.116). Although these data are inconsistent with previous reports [7– 9], the function majority of these patients have had concomitant different valve lesions, such as stenosis or regurgitation [10 –12], which affect the atrial and ventricular function. We showed that there was significant difference in plasma BNP levels between MS and AS group. This result has demonstrated that plasma BNP levels reflect pressure overload in left ventricle and hypertrophic changes in myocardium. An interesting finding in our results is that the patients, who showed high in plasma BNP levels before surgery, suffered poor recovery of clinical symptom during interim period following operation, retrospectively. Moreover, NYHA functional class has not improved in spite of the recovery of cardiac functions. Especially, patients (n = 22) who have improved from NYHA III or II to NYHA I, showed lower plasma BNP levels compared with others (n = 13) (108.6 F 16.5 vs. 431.0 F 145.6, P = 0.0074). These results have indicated that a role of BNP is as general indicator of cardiac structural disease rather than specific indicator of systolic dysfunction [13]. The major limitation in this study is associated with NYHA functional class based on the short-term observation. Furthermore, the relationship between plasma BNP levels and left ventricular function or clinical symptom is a concept difficult to define or standardize. Therefore, further additional investigations may be necessary and we have suggested that the importance of plasma BNP levels becomes clear by long-term prognosis observation. We do not recommend valve surgery in asymptomatic patients at this time due to the lack of evidence for benefit of early surgery. The goal of valvular heart disease is to determine
24
M. Watanabe et al. / International Journal of Cardiology 96 (2004) 21–24
the optimal surgical timing when long-term survival and improvement of clinical symptom can be expected. In conclusion, in the clinical cases that were studied for the relationship between plasma BNP levels and valvular heart disease, patients with high plasma BNP levels significantly impaired the improvement of clinical symptoms after surgery. The results of the present study, therefore, have suggested that valvular surgery may be necessary for patients with high plasma BNP levels (>200 pg/ml) even though they entirely have normal cardiac functions.
References [1] Sudoh T, Kangawa K, Minamino N, HM. A new natriuretic peptide in porcine brain. Nature 1988;332:78 – 81. [2] Yasue H, Yoshimura M, Sumida H, et al. Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation 1994;90:195 – 203. [3] Yoshimura M, Yasue H, Ogawa H. Pathophysiological significance and clinical application of ANP and BNP in patients with heart failure. Canadian Journal of Physiology and Pharmacology 2001; 79:730 – 5. [4] Lainchbury JG, Espiner EA, Nicholls MG, Richards AM. Cardiac hormones: diagnostic and therapeutic potential. New Zealand Medical Journal 1997;110(1046):219 – 21.
[5] Hirata Y, Matsumoto A, Aoyagi T, et al. Measurement of plasma brain natriuretic peptide level as a guide for cardiac overload. Cardiovascular Research 2001;15;51(3):585 – 91. [6] Struthers AD. Introducing a new role for BNP: as a general indicator of cardiac structural disease rather than a specific indicator of systolic dysfunction only. Heart 2002;87:97 – 8. [7] Lubien E, DeMaria A, Krishnaswamy P, et al. Utility of B-natriuretic peptide in detecting diastolic dysfunction: comparison with Doppler velocity recordings. Circulation 2002;105:595 – 601. [8] Inoue T, Sakuma M, Yaguchi I, et al. Early recanalization and plasma brain natriuretic peptide as an indicator of left ventricular function after acute myocardial infarction. American Heart Journal 2002; 143(5):790 – 6. [9] Waku S, Iida N, Ishihara T. Significance of brain natriuretic peptide measurement as a diagnostic indicator of cardiac function. Methods of Information in Medicine 2000;39(3):249 – 53. [10] Aikawa K, Otto CM. Timing of surgery in aortic stenosis. Progress in Cardiovascular Disease 2001;43(6):477 – 93. [11] Carabello BA. Progress in mitral and aortic regurgitation. Progress in Cardiovascular Disease 2001;43(6):457 – 75. [12] Talwar S, Downie PF, Squire IB, Davies JE, Barnett DB, Ng LL. Plasma N-terminal pro BNP and cardiotrophin-1 are elevated in aortic stenosis. European Journal of Heart Failure 2001;3(1):15 – 9. [13] Struthers AD. Introducing a new role for BNP: as a general indicator of cardiac structural disease rather than a specific indicator of systolic dysfunction only. Heart 2002;87:97 – 8.
Is measurement of plasma brain natriuretic peptide levels a useful test to detect for surgical timing of valve disease? Masazumi Watanabe *, Mikiko Murakami, Hitoshi Furukawa, Hideki Nakahara Department of Cardiovascular Surgery, Tokyo Metropolitan Hiroo General Hospital, 2-34-10 Ebisu, Shibuya-ku, Tokyo 150-0013, Japan Received 25 December 2002; received in revised form 23 June 2003; accepted 25 July 2003
Abstract Background: The optimal timing of valve surgery is very important. In patients who are severely symptomatic, the marked improvement in symptomatic status observed following successful valve surgery. However, in patients with no or only mild symptoms, the decision is more difficult. The aim of this retrospective study was to determine whether the measurement of plasma brain natriuretic peptides (BNP) levels is useful to decide surgical timing for valve disease. Methods: Fifty-one patients with valve disease underwent single valve surgery (mitral stenosis, MS, 13; mitral regurgitation, MR, 16; aortic stenosis, AS, 14; aortic regurgitation, AR, 8 patients). Blood samples, echocardiographic and cardiac catheterization data were obtained before operation and echocardiographic examination were performed after 1-year of operations. Results: In patients subjected to single heart valve surgery, plasma BNP mean levels were 214.6 F 48.5 pg/ml. In plasma BNP levels, there was only significant difference between MS and AS group (MS 67.5 F 9.7 vs. AS 314.3 F 112.0 pg/ml, P = 0.04). There were no relationships between plasma BNP levels and pre-operative cardiac functions. After 1-year of the valve surgery, NYHA functional class was reduced in 36 patients (70.6%) and plasma BNP levels before the surgery significantly correlated with post-operative NYHA functional class. Conclusions: In this retrospective study, patients with high plasma BNP levels significantly impaired the improvement of clinical symptoms after surgery. We have suggested that plasma BNP levels is useful for detecting asymptomatic valvular disease, and is a clinical marker useful in determining the optimal surgical timing. D 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: BNP; Valve disease; Surgical timing; NYHA; Cardiac function
1. Introduction The optimal timing of valve surgery is very important. Performance of operation ‘‘too late’’ may result in the development of severe, irreversible left ventricular dysfunction, which may fail to improve or actually worsen following valve surgery; the outcome may be one of increased operative mortality, impaired long-term survival, and severe congestive heart failure in operative survivors. Conversely, performance of early valve surgery, before it is clearly necessary, places the patient at unnecessary risk of the many complications of the operation. Brain natriuretic peptide (BNP), a family of peptides with structural and biologic homologies to previously identified atrial natriuretic peptide (ANP), has been found in human cardiac tissue and plasma
* Corresponding author. Tel.: +81-33-444-1181; fax: +81-33-444-3196. E-mail address: [email protected] (M. Watanabe). 0167-5273/$ - see front matter D 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2003.07.009
[1]. In humans, BNP is expressed predominantly in the ventricles of failing hearts [2]. Recent studies [3,4] have demonstrated that the plasma BNP levels reflect left ventricular pressure and correlates to disease severity and prognosis. Evaluating of operative timing for valvular heart disease is a complex process because of the variety of valves available and the multiple number of valve-related events including left ventricular conditions that must be considered. The purpose of this study was to assess whether the measurement of plasma BNP levels is a useful test to detect for surgical timing of valve disease.
2. Patients and methods The study was approved by the institutional review board, and written informed consent was obtained from all patients. Subjects included 51 patients (28 males, 23 females) undergoing single valve surgery for heart valve disease
22
M. Watanabe et al. / International Journal of Cardiology 96 (2004) 21–24
Table 1 Patients’ characteristics
AR, aortic regurgitation (n = 8); AS, aortic stenosis (n = 14); MR, mitral regurgitation (n = 16); MS, mitral stenosis (n = 13); Paw, pulmonary wedge pressure; LVEDP, left ventricular endo-diastolic pressure; LVDd, left ventricular diastolic dimension; LVM, left ventricular mass; LV mass volume was calculated with the following formula: 0.8[1.05{(LV end-diastolic dimension + ventricular septum + LV posterior wall)3 (LV end-diastolic dimension)3}] + 0.06). *, P = 0.04; **, P = 0.03; $, P = 0.02; #, P = 0.009; ##, P = 0.0006.
(mitral stenosis, MS, MVA = 1.0 F 0.3 cm2, 13 patients; mitral regurgitation, MR, moderate 6, severe 10, 16 patients; aortic stenosis, AS, max PG = 82 F 10.8 mmHg, 14 patients; aortic regurgitation, AR, moderate 3, severe 5, 8 patients). The mean F standard error (S.E.) age at valve surgery was 61.0 F 1.7 years (range: 17 – 82 years). All 51 patients were examined by echocardiography before the operation and after 1-year of the operation. Blood samples obtained before operation was assayed for plasma BNP levels. Plasma BNP levels were measured with a specific immunoradiometric assay for human BNP (Shiono ANP kit and Shiono BNP kit, Shionogi Co.) Follow-up consisted of echocardiography examinations after 1-year of surgery.
3. Statistical analyses Statistical analysis was performed using a PC computer with Statview IV statistical software (Abacus Concepts, Berkeley, CA). All values are expressed as mean F S.E. Data were analyzed using repeated measures analysis of variance and Dunnett’s t-test where appropriate. P values less than 0.05 were considered statistically significant. Regression analysis was performed with the least-square method and a case-wise deletion of missing data.
4. Results There were no deaths and all patients are alive and well. In patients subjected to single heart valve surgery, plasma BNP mean levels were 214.6 F 48.5 pg/ml (plasma BNP levels in normal healthy people offered by Mitsubishi Kagaku Bio-Clinical Laboratories, Inc.; BNP < 18.4 pg/ ml). The clinical characteristics of the study patients are listed in Table 1. There were no correlations between plasma BNP levels and echocardiographic parameters, cath data (LVDd: r 2 = 0.005, wall thickness: r 2 = 0.107, ejection fraction: r 2 = 0.012, LV mass: r 2 = 0.025). The mean F S.E. disease period (pointed out valvular lesion) was 6.1 F 1.0 year. No relationship existed between plasma BNP levels and disease period (r 2 = 0.075; AR: r 2 = 0.322, AS: r 2 = 0.198, MR: r 2 = 0.064, MS: r 2 = 0.023). In plasma BNP levels, there was only significant difference between MS and AS group. Thirty-one patients were classified in New York Heart Association (NYHA) functional class II (41.2%) or I (19.6%), 20 in class IV (11.8%) or III (27.5%) before surgery. There were no relationships between plasma BNP levels and pre-operative cardiac functions (Table 2).
Table 2 Correlation between cardiac function and plasma BNP levels Group
AR AS MR MS
Cardiac catheter data
Echocardiographic data
Paw
LVEDP
LVDd
EF
LVM
0.407 0.043 0.484 0.099
0.003 0.062 0.004 0.018
0.061 0.283 0.024 0.025
0.003 0.054 0.060 0.075
2
r = 0.212 0.125 0.320 0.146
Paw, pulmonary wedge pressure; LVEDP, left ventricular endo-diastolic pressure; LVDd, left ventricular diastolic dimension; LVM, left ventricular mass; LV mass volume was calculated with the following formula: 0.8[1.05{(LV end-diastolic dimension + ventricular septum + LV posterior wall)3 (LV end-diastolic dimension)3}] + 0.06).
Fig. 1. This graph shows the relationship between NYHA and plasma BNP levels before surgery. There were significant differences in plasma BNP levels among groups (NYHA I vs. III and IV, P = 0.04; NYHA II vs. IV, P = 0.001; NYHA III vs. IV, P = 0.001).
M. Watanabe et al. / International Journal of Cardiology 96 (2004) 21–24
Fig. 2. This graph shows the relationship between NYHA after surgery and plasma BNP levels. There were significant differences in plasma BNP levels among groups (NYHA I vs. III, P < 0.0001; NYHA II vs. III, P = 0.0001; NYHA I vs. II, P = 0.049).
However, in NYHA IV and III, plasma BNP levels were significantly higher than NYHA II and I (NYHA I: 56.5 F 17.1, II: 105.6 F 15.9, III: 412.6 F 136.4, IV: 397.8 F 201.7 pg/ml, Fig. 1). With respect to cardiac functional data, there were no significant differences in NYHA functional class. After 1-year of the valve surgery, NYHA functional class was reduced in 36 patients (70.6%), unchanged in 14 patients (27.5%) and getting worth in one patient (to class II from class I). NYHA functional class after surgery was not correlated with post-operative left ventricular ejection fraction (NYHA I: 64.8 F 3.3, NYHA II: 62.9 F 3.3, NYHA III: 60.8 F 7.1%). In retrospective analysis, there were no significant differences in pre-operative paw pressure, left ventricular end-diastolic pressure, left ventricular ejection fraction and left ventricular mass between postoperative NYHA III and I. However, plasma BNP levels before surgery significantly correlated with post-operative NYHA functional class (NYHA I: 89.2 F 12.8, II: 157.0 F 68.3, III: 1025.3 F 204.4 pg/ml, Fig. 2).
5. Discussion People with valvular heart disease are living longer, with less morbidity, than ever before. Valvular heart disease may first be diagnosed in the setting of an acute medical event, such as heart failure. The diagnosis of valvular heart disease is initially suspected before the onset of overt symptoms on the basis of the physical examination finding. Advances in surgical techniques and a better understanding of timing for surgical intervention account for increased rates of survival. Performance of operation ‘‘too late’’ inevitably causes left ventricular damage, eventually resulting in death. In this sense, the left ventricle is the ‘‘end
23
organ’’ damaged by underlying valvular disease. It is clear that some patients with mild or moderate valve lesions require surgery even though they are entirely asymptomatic. Our results also suggest that early surgery lead to good prognosis. However, in patients with no or only mild symptoms, the decision of surgery is more difficult. These different lesions such as stenosis and regurgitation result in different loading conditions, different pathophysiologies, and have different means for surgical correction. Therefore, it is thought that an indicator, which decides surgical timing, is required. In previous reports, measurement of plasma BNP levels was a useful test to detect for significant valve disease, LVH, and LV diastolic dysfunction [5,6]. Especially, plasma BNP levels could predict diastolic abnormalities in patients with normal systolic function [7]. We, in this retrospective study, examined whether plasma BNP levels is a useful marker to decide surgical timing for valve disease. Our results showed that patients with valve disease increased plasma BNP levels independent of cardiac catheterization data. In the present study, there was also no significant difference in plasma BNP levels between patients with left ventricular dysfunction (EF < 50%, n = 8) and normal function (>50%, n = 43) (EF < 50%:>50% = 181.6 F 49.0:391.8 F 155.3, P = 0.116). Although these data are inconsistent with previous reports [7– 9], the function majority of these patients have had concomitant different valve lesions, such as stenosis or regurgitation [10 –12], which affect the atrial and ventricular function. We showed that there was significant difference in plasma BNP levels between MS and AS group. This result has demonstrated that plasma BNP levels reflect pressure overload in left ventricle and hypertrophic changes in myocardium. An interesting finding in our results is that the patients, who showed high in plasma BNP levels before surgery, suffered poor recovery of clinical symptom during interim period following operation, retrospectively. Moreover, NYHA functional class has not improved in spite of the recovery of cardiac functions. Especially, patients (n = 22) who have improved from NYHA III or II to NYHA I, showed lower plasma BNP levels compared with others (n = 13) (108.6 F 16.5 vs. 431.0 F 145.6, P = 0.0074). These results have indicated that a role of BNP is as general indicator of cardiac structural disease rather than specific indicator of systolic dysfunction [13]. The major limitation in this study is associated with NYHA functional class based on the short-term observation. Furthermore, the relationship between plasma BNP levels and left ventricular function or clinical symptom is a concept difficult to define or standardize. Therefore, further additional investigations may be necessary and we have suggested that the importance of plasma BNP levels becomes clear by long-term prognosis observation. We do not recommend valve surgery in asymptomatic patients at this time due to the lack of evidence for benefit of early surgery. The goal of valvular heart disease is to determine
24
M. Watanabe et al. / International Journal of Cardiology 96 (2004) 21–24
the optimal surgical timing when long-term survival and improvement of clinical symptom can be expected. In conclusion, in the clinical cases that were studied for the relationship between plasma BNP levels and valvular heart disease, patients with high plasma BNP levels significantly impaired the improvement of clinical symptoms after surgery. The results of the present study, therefore, have suggested that valvular surgery may be necessary for patients with high plasma BNP levels (>200 pg/ml) even though they entirely have normal cardiac functions.
References [1] Sudoh T, Kangawa K, Minamino N, HM. A new natriuretic peptide in porcine brain. Nature 1988;332:78 – 81. [2] Yasue H, Yoshimura M, Sumida H, et al. Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation 1994;90:195 – 203. [3] Yoshimura M, Yasue H, Ogawa H. Pathophysiological significance and clinical application of ANP and BNP in patients with heart failure. Canadian Journal of Physiology and Pharmacology 2001; 79:730 – 5. [4] Lainchbury JG, Espiner EA, Nicholls MG, Richards AM. Cardiac hormones: diagnostic and therapeutic potential. New Zealand Medical Journal 1997;110(1046):219 – 21.
[5] Hirata Y, Matsumoto A, Aoyagi T, et al. Measurement of plasma brain natriuretic peptide level as a guide for cardiac overload. Cardiovascular Research 2001;15;51(3):585 – 91. [6] Struthers AD. Introducing a new role for BNP: as a general indicator of cardiac structural disease rather than a specific indicator of systolic dysfunction only. Heart 2002;87:97 – 8. [7] Lubien E, DeMaria A, Krishnaswamy P, et al. Utility of B-natriuretic peptide in detecting diastolic dysfunction: comparison with Doppler velocity recordings. Circulation 2002;105:595 – 601. [8] Inoue T, Sakuma M, Yaguchi I, et al. Early recanalization and plasma brain natriuretic peptide as an indicator of left ventricular function after acute myocardial infarction. American Heart Journal 2002; 143(5):790 – 6. [9] Waku S, Iida N, Ishihara T. Significance of brain natriuretic peptide measurement as a diagnostic indicator of cardiac function. Methods of Information in Medicine 2000;39(3):249 – 53. [10] Aikawa K, Otto CM. Timing of surgery in aortic stenosis. Progress in Cardiovascular Disease 2001;43(6):477 – 93. [11] Carabello BA. Progress in mitral and aortic regurgitation. Progress in Cardiovascular Disease 2001;43(6):457 – 75. [12] Talwar S, Downie PF, Squire IB, Davies JE, Barnett DB, Ng LL. Plasma N-terminal pro BNP and cardiotrophin-1 are elevated in aortic stenosis. European Journal of Heart Failure 2001;3(1):15 – 9. [13] Struthers AD. Introducing a new role for BNP: as a general indicator of cardiac structural disease rather than a specific indicator of systolic dysfunction only. Heart 2002;87:97 – 8.