European Heart Journal Advance Access published online on April 4, 2007
European Heart Journal, doi:10.1093/eurheartj/ehm048
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Evaluation of cardiac sympathetic nerve activity and left ventricular remodelling in patients with dilated cardiomyopathy on the treatment containing carvedilol
1 Department of Cardiovascular Medicine, Gunma University School of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma 371-0034, Japan
2 Department of Internal Medicine, Cardiovascular Hospital of Central Japan, Gunma, Japan
Received 18 February 2006; revised 2 February 2007; accepted 1 March 2007.
* Corresponding author. Tel: +81 27 220 8145/+81 277 54 5344 (home); fax: +81 27 220 8158. E-mail address: s-kasama{at}bay.wind.ne.jp
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
Aims: It has been reported that carvedilol improves cardiac sympathetic nerve activity (CSNA) in patients with dilated cardiomyopathy (DCM). However, the influence of carvedilol on cardiac 123I-meta-iodobenzylguanidine (MIBG) scintigraphic findings and left ventricular (LV) remodelling has not been determined in DCM patients.
Methods and results: In 30 patients with DCM and 10 normal controls, the delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined by 123I-MIBG scintigraphy. In addition, the left ventricular end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were calculated by echocardiography. In the DCM patients, the regional defect score index (RDSI), regional washout rate index (RWRI), and wall motion score index (WMSI) were also determined to evaluate regional adrenergic dysfunction and wall motion. Examinations were repeated in all DCM patients after standard treatment containing carvedilol at a dose of 10–20 mg/day (mean dose: 16 ± 4 mg/day) for a mean of 12 ± 1 months. Both the 123I-MIBG scintigraphic and echocardiographic parameters were significantly worse in the DCM patients than the normal control subjects. After treatment, all of these parameters improved significantly in the DCM patients. There was a significant correlation between the changes of 123I-MIBG findings and changes of the LVEDV and LVESV after treatment. Moreover, there was a significant correlation between changes of the WMSI and those of the RDSI or RWRI in DCM patients.
Conclusion: Both 123I-MIBG scintigraphic parameters and echocardiographic parameters were improved in the DCM patients. There was a significant correlation between the changes of 123I-MIBG scintigraphic and echocardiographic findings after treatment. These findings implicate that long-term, including carvedilol, therapy can improve both CSNA and LV remodelling in patients with DCM.
Key Words: 123I-meta-iodobenzylguanidine • Dilated cardiomyopathy • Carvedilol
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
The prognosis of patients with idiopathic dilated cardiomyopathy (DCM) remains poor. Activation of the sympathetic nervous system is one of the cardinal pathophysiological abnormalities associated with congestive heart failure (CHF).1 Since Waagstein et al.2 reported that some patients with decompensated CHF showed clinical improvement after administration of ß-blockers, various studies have demonstrated that ß-blocker therapy can have a beneficial effect in selected patients with CHF.3–7
Cardiac imaging with 123I-meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, is a useful tool for detecting abnormalities of the myocardial adrenergic nervous system in patients with CHF.8,9 A large number of studies have suggested that treatment of heart failure can improve cardiac sympathetic nerve activity (CSNA) in CHF patients, as demonstrated by cardiac 123I-MIBG scintigraphy.10–18 The third-generation ß-blocker carvedilol has been reported to improve CSNA in a rat model of DCM as well as in DCM patients with heart failure.13–15,19 However, the effect of carvedilol on cardiac 123I-MIBG scintigraphic parameters and left ventricular (LV) remodelling has not been determined in patients with DCM.
Accordingly, the present study was performed to evaluate whether standard treatment containing carvedilol could improve both CSNA and LV remodelling in patients with idiopathic DCM.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
Patients
Forty-two patients with DCM and a left ventricular ejection fraction (LVEF) <45% were admitted to our institution with their first episode of CHF between November 2000 and August 2003. A detailed history and physical examination were obtained prior to enrollment in this prospective, non-randomized, open-label study. Chest radiography, standard electrocardiography, echocardiography, and 201Tl and 123I-MIBG scintigraphy were performed in all patients. The patients were in New York Heart Association (NYHA) functional class II or III at the time of enrollment. Patients were excluded from the study for the following reasons: heart failure NYHA functional class IV (three patients were excluded); coronary artery disease diagnosed with evidence of any coronary artery stenosis >50% by angiography (one patient); active myocarditis diagnosed by LV endomyocardial biopsy specimens (two patients); systemic arterial hypertension (one patient); and diabetes or glucose intolerance (three patients). Furthermore, none of the patients had a history of alcohol abuse, congenital heart disease, and severe liver or kidney disease. Therefore, 32 of 42 patients were enrolled in this trial at subacute phase.
Five patients were already taking ß-blockers when admitted to our institution, but their ß-blockers were discontinued immediately after hospitalization. None of the patients was using spironolactone before being hospitalized. During the acute phase, all of the patients were treated with standard therapy for heart failure. After heart failure was controlled, all of the patients were being treated with an angiotensin-converting enzyme (ACE)-inhibitor and with diuretics, whereas some were also receiving digitalis (n = 2) and vasodilators (isosorbide dinitrate; n = 3). None of the patients was treated with tricyclic anti-depressants or other serotonin reuptake inhibitors.
All control subjects (seven men and three women aged 48–62 years) who had been hospitalized for suspected angina pectoris had low-risk profiles with normal cardiovascular examination results, including echocardiography, coronary angiography, and left ventriculography. No control subject was on any drug treatment for cardiac disease or had a cardiac disease that could possibly affect haemodynamic studies. The study was approved by the Ethical Review Board of our institution, and written informed consent was obtained from each subject.
Study protocol
Carvedilol was started at a dose of 1.25–2.5 mg/day in all of the DCM patients and the dose was gradually increased to a maximum of 10–20 mg/day (mean: 16 ± 4 mg/day). Examinations were performed before and after carvedilol treatment for a mean of 12 ± 1 months in all of the DCM patients, while examinations were done only once (at the time when haemodynamics was normal) in the control group.
Echocardiography
Echocardiography was performed with a commercially available sector scanner (SONOS 5500, Hewlett-Packard) and the images were recorded on half-inch S-VHS tape. Two experienced echocardiographers who had no knowledge about the study performed all the measurements independently. Left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and LVEF were calculated using the modified method of Simpson.20 The mean interobserver and intraobserver differences of LVEDV were 2 ± 4 and 0 ± 2 mL, respectively, those of LVESV were 1 ± 5 and 0 ± 2 mL, respectively, and those of LVEF were 2 ± 4% and 0 ± 3%, respectively. Moreover, interobserver and intraobserver variability in these measurements were assessed by linear regression, and the levels of agreement were very high [LVEDV: r = 0.90 (P = 0.002) and r = 0.94 (P = 0.000), respectively; LVESV: r = 0.90 (P = 0.004) and r = 0.93 (P = 0.000), respectively; LVEF: r = 0.90 (P = 0.002) and r = 0.93 (P = 0.000), respectively].
Regional wall motion was assessed by using the 17-segment method recommended by American Heart Association.21 In each segment, systolic wall motion was visually graded with the following scale: 0, normal; 1, mild hypokinesis; 2, moderate hypokinesis; 3, severe hypokinesis or akinesia; 4, dyskinesia. The regional wall motion score index (WMSI) was calculated as an average of the wall motion scores in these 17 segments.
Cardiac 123I-MIBG scintigraphy
The method of 123I-MIBG imaging has been described previously.16–18 In brief, patients were injected intravenously with 111 MBq of 123I-MIBG (Daiichi Radioisotope Laboratories, Tokyo, Japan) while in the supine position. At 15 min and at 4 h after injection, the anterior planar and single photon emission computed tomography (SPECT) images were obtained with a single-head gamma camera (Millennium MPR, GE Medical Systems, Waukesha, WI, USA).
Global analysis of 123I-MIBG scintigraphy
The heart/mediastinum count ratio (H/M ratio) was determined from the delayed anterior planar 123I-MIBG image. The global washout rate (WR) was calculated using the following formula: {([H] – [M])early – ([H] – [M])delayed} / ([H] – [M])early x 100(%), where [H] = mean count per pixel in the LV and [M] = mean count per pixel in the upper mediastinum.
Myocardial SPECT images of each subject were divided into 17 segments as was done for echocardiography. Regional tracer uptake was assessed semi-quantitatively using the following 5-point scale: 0, normal uptake; 1, mildly reduced uptake; 2, moderately reduced uptake; 3, severely reduced uptake; 4, no uptake. In addition, the delayed total defect score (TDS) was calculated as the sum of all segmental defect scores.
Analysis was done in a blinded fashion by two independent observers with no knowledge of the clinical status or therapy of the subjects. The mean interobserver and intraobserver differences of TDS were 2 ± 3 and 0 ± 1, respectively. Moreover, interobserver and intraobserver variability of TDS were assessed by linear regression, and the levels of agreement were very high (r = 0.90, P = 0.001 and r = 0.94, P = 0.000, respectively).
Regional analysis of 123I-MIBG scintigraphy
To evaluate regional adrenergic dysfunction in the DCM patients on SPECT images, we calculated a regional defect score (RDS) for each of the 17 segments, as was done in the echocardiographic study. In addition, the regional washout rate (RWR) was calculated for each of the 17 segments using the following formula: {(mean count per pixel in early images) – (mean count per pixel in delayed images)} / (mean count per pixel in early images). Then the regional defect score index (RDSI) and regional washout rate index (RWRI) were calculated as the average RDS and RWR of the 17 segments, respectively.
Plasma brain natriuretic peptide concentration
Blood samples were collected in test tubes containing EDTA after the subjects had rested in a supine position for at least 30 min. Plasma was separated by centrifugation and frozen at –84°C until measurement. Then the plasma concentration of brain natriuretic peptide (BNP) was measured with a specific immunoradiometric assay for human BNP using a commercial kit (normal range <20 pg/mL) (Shionogi, Osaka, Japan), as previously reported.17,18,22
Statistical analysis
Statistical analysis was performed using SPSS 12.0 for Windows (SPSS Inc.). Numerical results are expressed as the mean ± SD. Comparison of baseline categorical data between the two groups was done by the one-sided chi-square contingency table method and differences between continuous variables were evaluated using the unpaired t-test and one-way ANOVA. The effects of carvedilol treatment were assessed by the paired t-test. Changes of NYHA functional class were assessed using the Wilcoxon matched pairs signed ranks test. Linear regression analysis was employed to determine the relationship between continuous variables. The relationships between changes of WMSI and both changes of RDSI and RWRI were assessed using the Spearman rank correlation coefficient (rs). In all analyses, P < 0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
Clinical characteristics
One DCM patient developed cerebral embolism and one patient died of CHF after 3 months of the treatment. Thus, 30 out of 32 patients (20 men and 10 women with a mean age of 55 ± 11 years, range: 38–70 years) enrolled in the trial completed the entire protocol (Table 1). None of the 30 patients changed their baseline cardiac medication (apart from gradually increasing the dose of carvedilol) during the follow-up period. The mean dose of the ACE-inhibitor enalapril was 7.3 ± 2.8 mg/day (n = 16), while that of perindopril was 2.3 ± 0.7 mg/day (n = 14). The mean dose of furosemide was 53 ± 21 mg/day (n = 30), while the mean dose of spironolactone was only 25 mg/day (n = 10). In this study, no patients were treated with angiotensin-receptor blockers.
|
The 123I-MIBG scintigraphic data, echocardiographic data, and plasma BNP concentrations of the DCM patients and normal control subjects are shown in Table 1. All of these parameters were significantly worse in the DCM patients when compared with the normal controls.
Heart rate, blood pressure, and NYHA functional class of the DCM patients before and after treatment
The heart rate was significantly reduced in the DCM patients group (68 ± 11 b.p.m.) when compared with the baseline value (79 ± 13 b.p.m.) (P = 0.000). However, there were no significant changes of the systolic and diastolic blood pressures (123 ± 17 mmHg vs. 120 ± 14 mmHg, and 74 ± 9 mmHg vs. 71 ± 7 mmHg, respectively).
The NYHA functional class of the DCM patients is shown in Table 2. Significant improvement of the NYHA functional class relative to baseline occurred after the treatment.
|
BNP concentration of the DCM patients before and after treatment
Plasma BNP concentrations are shown in Table 2. The plasma BNP concentration was significantly decreased after the treatment relative to baseline.
Cardiac 123I-MIBG scintigraphic and echocardiographic findings of the DCM patients before and after treatment
The TDS, H/M ratio, and WR data for the DCM patients are listed in Table 3 and Figure 1. The TDS and WR were significantly decreased by the treatment when compared with the baseline value. The H/M ratio was significantly increased by the treatment when compared with baseline.
|
|
The LVEDV, LVESV, and LVEF data for the DCM patients are displayed in Table 3. The LVEDV and LVESV were significantly decreased after the treatment when compared with the baseline value, while LVEF significantly increased after the treatment.
Relationship between LV volume and global 123I-MIBG scintigraphic findings before and after treatment
There were significant correlations between the changes of the 123I-MIBG scintigraphic findings after the treatment and the changes of the LVEDV (Figure 2) or the LVESV (Figure 3).
|
LVEDV = the value of LVEDV after treatment – pretreatment value of LVEDV;
|
Relationship between WMSI and regional 123I-MIBG scintigraphic findings before and after treatment
According to Spearman's rank correlation coefficient analysis, there was a significant correlation between the changes of WMSI after the treatment and the changes of the RDSI or RWRI (Figure 4).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
Idiopathic DCM is characterized by ventricular dilation and systolic dysfunction, and it generally has a poor prognosis. The 1-year mortality rate of patients with idiopathic DCM can be as high as 25%, while the 5-year mortality ranges from 20 to 50%.23 Earlier detection of this disease and introduction of ß-blocker therapy may have led to a recent improvement of the prognosis.3–7 The beneficial effects of ß-blockers on DCM include the following: (i) increased supply of energy to the myocardium for synthesis and repair; (ii) improvement of diastolic relaxation, filling, and compliance; (iii) inhibition of sympathetically mediated vasoconstriction via prostaglandin and renin; and (iv) protection against catecholamine-induced myocardial damage and necrosis.24,25 It has been reported that ß-blockers have various haemodynamic and energetic benefits,26 as well as enhancing cell-mediated immunity and improving T cell function.27 These multiple actions lead to a reduction in the risk of death and the risk of hospitalization for cardiovascular disease.3–7
123I-MIBG is an analogue of the adrenergic neuron blocking agent guanethidine, and it is thought to utilize the same myocardial uptake and release mechanisms as norepinephrine.28 The myocardial norepinephrine concentration and 123I-MIBG imaging findings are correlated in patients with DCM,8 so cardiac 123I-MIBG imaging is a useful tool for detecting abnormalities of the myocardial adrenergic nervous system in these patients.8,9 Several reports have suggested that ACE-inhibitors,10,11,18 ß-blockers,11–15 spironolactone,16 and angiotensin-receptor blockers17 can improve CSNA in patients with heart failure, based on cardiac 123I-MIBG scintigraphic findings. The basic pharmacological action of the third-generation ß-blocker carvedilol differs considerably from that of other ß-blockers. Carvedilol is a relatively non-selective ß1-, ß2-blocking agent, while it also blocks 
1-receptors29 and has antioxidant activity.30 Carvedilol may inhibit the cardiac adrenergic drive more potently than other ß-blockers, because Gilbert et al.31 have reported that carvedilol does not upregulate ß1-adrenergic receptors and that it blocks all adrenergic receptors. Furthermore, Watanabe et al.19 reported that carvedilol directly improves cardiac neuronal uptake of norepinephrine in a rat model of DCM and that this action may increase the exposure of cardiac myocytes to norepinephrine. In this study, we examined whether standard treatment containing carvedilol could improve CSNA in DCM patients using 123I-MIBG scintigraphy, and we found that the TDS, H/M ratio, and WR were all improved by the treatment.
Kramer et al.32 have previously reported that sympathetic denervation of the adjacent non-infarcted regions contributes to LV remodelling in animal models with myocardial infarction. The same group also demonstrated that ß-blocker therapy improves adjacent regional innervation and preserves cardiac function.33 Although our subjects included patients with non-ischaemic DCM, we did not include any patients with myocardial infarction. Accordingly, we will need to study the effects of carvedilol on CSNA and LV remodelling after myocardial infarction in the future.
The plasma BNP level is a useful prognostic indicator in patients with CHF,34 since BNP is a ventricular hormone.35 Plasma BNP is reported to show a correlation with abnormalities of LVEF and LV end-diastolic pressure,35 as well as with LV mass.36 The decrease of circulating BNP that we detected after carvedilol treatment was presumably due to a decrease of LV filling pressure, improvement of LV remodelling, or both factors. The decrease of plasma BNP with carvedilol therapy may also have reflected improvement of LV diastolic function secondary to the amelioration of cardiac hypertrophy and fibrosis by this drug. Treatment of CHF guided by the plasma BNP level has been reported to reduce cardiovascular events,34 so a decrease of BNP may be associated with a better outcome, as has been shown in the previous studies of carvedilol.5–7 In the present study, plasma BNP was significantly decreased by the therapy in our patients with DCM, and the patients also showed improvement of heart failure as measured by the NYHA functional class.
In some previous studies, carvedilol was found to improve CSNA evaluated by 123I-MIBG scintigraphy in patients with DCM.13–15 Gerson et al.13 reported that there was no significant improvement of the H/M ratio and WR by carvedilol in patients with DCM, despite marked improvement of LV function and CSNA in patients with severe heart failure. In contrast, we found that the TDS, H/M ratio, and WR were all improved by the treatment. Such discrepancies may be partly due to differences of the patient population between the two studies, particularly a difference in the severity of heart failure. For example, the LVEF of our subjects was better than that of Gerson's group13 (33 ± 6% vs. 25 ± 8%, P = 0.000). Agostini et al.14 have also reported that carvedilol increases the H/M ratio and improves cardiac function in patients with DCM. Moreover, Cohen-Solal et al.15 found that carvedilol improves 123I-MIBG SPECT findings and decreases the LV diameter in heart failure patients compared with placebo treatment. However, there have been no previous reports of a correlation between CSNA and LV volume or regional wall motion parameters in patients with DCM. Accordingly, the present study provided the first evidence of a relationship between CSNA and LV remodelling, as well as between regional adrenergic function and regional wall motion, during the treatment in patients with DCM. Further studies will be needed to confirm these findings in a larger group of patients.
The H/M ratio determined by 123I-MIBG scintigraphy was higher in our study than in the study of Merlet.9 In general, the 123I-MIBG used in Japan had a higher specific activity (1665–2035 MBq/mg) than that of other MIBG provided by CIS BIO-International,37 so the control value of the H/M ratio was significantly higher in this study than in Merlet's9 (2.44 ± 0.26 vs. 1.96 ± 0.33, P = 0.001). Although no-carrier-added 123I-MIBG scintigraphy, with a greater specific activity, has been tested in animal models of heart failure in Europe,38 such researches has not been performed in Japan.
Currently, many independent reports from different centers around the world support the concept that 123I-MIBG myocardial scintigraphy provides useful information for assessing patients with heart failure. This modality seems to be valuable for predicting the prognosis and for estimating the long-term efficacy of therapy. However, quantitative 123I-MIBG parameters differ between institutions and between instruments, and this tracer is not widely available. For these reasons, cardiac 123I-MIBG has not yet achieved broad clinical acceptance, and the evidence supporting the clinical value of this imaging technique remains inadequate. We believe that multicenter studies are required to definitively establish the effectiveness of this imaging modality.
The small number of patients included in this study was a limitation. To determine the sample size, we referred to the previous studies in which ß-blocker carvedilol treatment of heart failure was favourable. Three manuscripts, Gerson et al.,13 Agostini et al.,14 and Nakamura et al.,30 enrolled 22, 22, and 23 patients, respectively, and determined that carvedilol improved the outcome of the DCM patients. Based on those studies, we selected this sample size. However, in the future, we need to study the long-term effects of carvedilol on CSNA and LV remodelling in a larger group of patients.
|
Conclusions |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
The TDS, H/M, and WR determined by 123I-MIBG scintigraphy were all significantly improved by the treatment. LV volume and cardiac function were also improved by the treatment, while the plasma BNP concentration showed a significant decrease. There was a significant correlation between changes of the 123I-MIBG scintigraphic parameters and changes of LV parameters during the treatment. These findings suggest that standard treatment containing carvedilol can improve CSNA and LV remodelling in patients with DCM.
Conflict of interest: none declared.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
- Thomas JA and Marks BH. (1978) Plasma norepinephrine in congestive heart failure. Am J Cardiol 41:233–243.[CrossRef][ISI][Medline]
- Waagstein F, Hjalmarson A, Varnauskas E, Wallentin I. (1975) Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy. Br Heart J 37:1022–1036.
[Abstract/Free Full Text] - CIBIS-II Investigators and Committees. (1999) The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 353:9–13.[CrossRef][ISI][Medline]
- MERIT-HF Study Group. (1999) Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 353:2001–2007.[CrossRef][ISI][Medline]
- Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, Shusterman NH. (1996) The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med 334:1349–1355.
[Abstract/Free Full Text] - Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL. Carvedilol Prospective Randomized Cumulative Survival Study Group. (2001) Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 344:1651–1658.
[Abstract/Free Full Text] - Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, Lubsen J, Lutiger B, Metra M, Remme WJ, Torp-Pedersen C, Scherhag A, Skene A. (2003) Carvedilol Or Metoprolol European Trial Investigators. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet 362:7–13.[CrossRef][ISI][Medline]
- Schofer J, Spielmann R, Schuchert A, Weber K, Schluter M. (1988) Iodine-123 meta-iodobenzylguanidine scintigraphy: a noninvasive method to demonstrate myocardial adrenergic nervous system disintegrity in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 12:1252–1258.[Abstract]
- Merlet P, Valette H, Dubois-Rande JL, Moyse D, Duboc D, Dove P, Bourguignon MH, Benvenuti C, Duval AM, Agostini D, Loisance D, Castaigne A, Syrota A. (1992) Prognostic value of cardiac metaiodobenzylguanidine imaging in patients with heart failure. J Nucl Med 33:471–477.
[Abstract/Free Full Text] - Somsen GA, van Vlies B, de Milliano PA, Borm JJ, van Royen EA, Endert E, Lie KI. (1996) Increased myocardial [123I]-metaiodobenzylguanidine uptake after enalapril treatment in patients with chronic heart failure. Heart 76:218–222.
[Abstract/Free Full Text] - Toyama T, Aihara Y, Iwasaki T, Hasegawa A, Suzuki T, Nagai R, Endo K, Hoshizaki H, Oshima S, Taniguchi K. (1999) Cardiac sympathetic activity estimated by 123I-MIBG myocardial imaging in patients with dilated cardiomyopathy after beta-blocker or angiotensin-converting enzyme inhibitor therapy. J Nucl Med 40:217–223.
[Abstract/Free Full Text] - Fukuoka S, Hayashida K, Hirose Y, Shimotsu Y, Ishida Y, Kakuchi H, Eto T. (1997) Use of iodine-123 metaiodobenzylguanidine myocardial imaging to predict the effectiveness of beta-blocker therapy in patients with dilated cardiomyopathy. Eur J Nucl Med 24:523–529.[ISI][Medline]
- Gerson MC, Craft LL, McGuire N, Suresh DP, Abraham WT, Wagoner LE. (2002) Carvedilol improves left ventricular function in heart failure patients with idiopathic dilated cardiomyopathy and a wide range of sympathetic nervous system function as measured by iodine 123 metaiodobenzylguanidine. J Nucl Cardiol 9:608–615.[CrossRef][ISI][Medline]
- Agostini D, Belin A, Amar MH, Darlas Y, Hamon M, Grollier G, Potier JC, Bouvard G. (2000) Improvement of cardiac neuronal function after carvedilol treatment in dilated cardiomyopathy: a 123I-MIBG scintigraphic study. J Nucl Med 41:845–851.
[Abstract/Free Full Text] - Cohen-Solal A, Rouzet F, Berdeaux A, Le Guludec D, Abergel E, Syrota A, Merlet P. (2005) Effects of carvedilol on myocardial sympathetic innervation in patients with chronic heart failure. J Nucl Med 46:1796–1803.
[Abstract/Free Full Text] - Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, Kurabayashi M. (2003) Effect of spironolactone on cardiac sympathetic nerve activity and left ventricular remodeling in patients with dilated cardiomyopathy. J Am Coll Cardiol 41:574–581.
[Abstract/Free Full Text] - Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, Kurabayashi M. (2005) Effects of candesartan on cardiac sympathetic nerve activity in patients with congestive heart failure and preserved left ventricular ejection fraction. J Am Coll Cardiol 45:661–667.
[Abstract/Free Full Text] - Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, Kurabayashi M. (2005) Effects of perindopril on cardiac sympathetic nerve activity in patients with congestive heart failure: comparison with enalapril. Eur J Nucl Med Mol Imaging 32:964–971.[CrossRef][ISI][Medline]
- Watanabe K, Takahashi T, Nakazawa M, Wahed MI, Fuse K, Tanabe N, Kodama M, Aizawa Y, Ashino H, Tazawa S. (2002) Effects of carvedilol on cardiac function and cardiac adrenergic neuronal damage in rats with dilated cardiomyopathy. J Nucl Med 43:531–535.
[Abstract/Free Full Text] - Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, Silverman NH, Tajik AJ. (1989) Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 2:358–367.[Medline]
- Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS. (2002) Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 105:539–542.
[Free Full Text] - Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Tange S, Suzuki T, Kurabayashi M. (2004) Dobutamine stress 99mTc-tetrofosmin quantitative gated SPECT predicts improvement of cardiac function after carvedilol treatment in patients with dilated cardiomyopathy. J Nucl Med 45:1878–1884.
[Abstract/Free Full Text] - Sugrue DD, Rodeheffer RJ, Codd MB, Ballard DJ, Fuster V, Gersh BJ. (1992) The clinical course of idiopathic dilated cardiomyopathy. a population-based study. Ann Intern Med 117:117–123.[ISI][Medline]
- Alderman J and Grossman W. (1985) Are beta-adrenergic-blocking drugs useful in the treatment of dilated cardiomyopathy? Circulation 71:854–857.
[Free Full Text] - Woodley SL, Gilbert EM, Anderson JL, O'Connell JB, Deitchman D, Yanowitz FG, Mealey PC, Volkman K, Renlund DG, Menlove R, Bristow MR. (1991) Beta-blockade with bucindolol in heart failure caused by ischaemic versus idiopathic dilated cardiomyopathy. Circulation 84:2426–2441.
[Abstract/Free Full Text] - Eichhorn EJ, Heesch CM, Barnett JH, Alvarez LG, Fass SM, Grayburn PA, Hatfield BA, Marcoux LG, Malloy CR. (1994) Effect of metoprolol on myocardial function and energetics in patients with nonischemic dilated cardiomyopathy: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 24:1310–1320.[Abstract]
- Maisel AS. (1994) Beneficial effects of metoprolol treatment in congestive heart failure. reversal of sympathetic-induced alterations of immunologic function. Circulation 90:1774–1780.
[Abstract/Free Full Text] - Wieland DM, Wu J, Brown LE, Mangner TJ, Swanson DP, Beierwaltes WH. (1980) Radiolabeled adrenergic neuron-blocking agents: adrenomedullary imaging with [131I]iodobenzylguanidine. J Nucl Med 21:349–353.
[Abstract/Free Full Text] - Ruffolo RR Jr, Gellai M, Hieble JP, Willette RN, Nichols AJ. (1990) The pharmacology of carvedilol. Eur J Clin Pharmacol 38:S82–S88.[CrossRef][ISI][Medline]
- Nakamura K, Kusano K, Nakamura Y, Kakishita M, Ohta K, Nagase S, Yamamoto M, Miyaji K, Saito H, Morita H, Emori T, Matsubara H, Toyokuni S, Ohe T. (2002) Carvedilol decreases elevated oxidative stress in human failing myocardium. Circulation 105:2867–2871.
[Abstract/Free Full Text] - Gilbert EM, Abraham WT, Olsen S, Hattler B, White M, Mealy P, Larrabee P, Bristow MR. (1996) Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart. Circulation 94:2817–2825.
[Abstract/Free Full Text] - Kramer CM, Nicol PD, Rogers WJ, Suzuki MM, Shaffer A, Theobald TM, Reichek N. (1997) Reduced sympathetic innervation underlies adjacent non-infarcted region dysfunction during left ventricular remodeling. J Am Coll Cardiol 30:1079–1085.[Abstract]
- Kramer CM, Nicol PD, Rogers WJ, Seibel PS, Park CS, Reichek N. (1999) Beta-blockade improves adjacent regional sympathetic innervation during post-infarction remodeling. Am J Physiol 277:H1429–H1434.[ISI][Medline]
- Tsutamoto T, Wada A, Maeda K, Hisanaga T, Maeda Y, Fukai D, Ohnishi M, Sugimoto Y, Kinoshita M. (1997) Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction. Circulation 96:509–516.
[Abstract/Free Full Text] - Yasue H, Yoshimura M, Sumida H, Kikuta K, Kugiyama K, Jougasaki M, Ogawa H, Okumura K, Mukoyama M, Nakao K. (1994) 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 90:195–203.
[Abstract/Free Full Text] - Kohno M, Horio T, Yokokawa K, Murakawa K, Yasunari K, Akioka K, Tahara A, Toda I, Takeuchi K, Kurihara N, Takeda T. (1992) Brain natriuretic peptide as a cardiac hormone in essential hypertension. Am J Med 92:29–34.[CrossRef][ISI][Medline]
- Nakata T, Wakabayashi T, Kyuma M, Takahashi T, Tsuchihashi K, Shimamoto K. (2005) Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in patients with heart failure. Eur J Nucl Med Mol Imaging 32:186–194.[CrossRef][ISI][Medline]
- Verberne HJ, de Bruin K, Habraken JB, Somsen GA, Eersels JL, Moet F, Booij J, van Eck-Smit BL. (2006) No-carrier-added versus carrier-added(123)I-metaiodobenzylguanidine for the assessment of cardiac sympathetic nerve activity. Eur J Nucl Med Mol Imaging 33:483–490.[CrossRef][ISI][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Kasama, T. Toyama, H. Sumino, M. Nakazawa, N. Matsumoto, Y. Sato, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, et al. Prognostic Value of Serial Cardiac 123I-MIBG Imaging in Patients with Stabilized Chronic Heart Failure and Reduced Left Ventricular Ejection Fraction J. Nucl. Med., June 1, 2008; 49(6): 907 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kasama, T. Toyama, H. Sumino, N. Matsumoto, Y. Sato, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi Additive Effects of Spironolactone and Candesartan on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients with Congestive Heart Failure J. Nucl. Med., December 1, 2007; 48(12): 1993 - 2000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kasama, T. Toyama, H. Sumino, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi Long-Term Nicorandil Therapy Improves Cardiac Sympathetic Nerve Activity After Reperfusion Therapy in Patients with First Acute Myocardial Infarction J. Nucl. Med., October 1, 2007; 48(10): 1676 - 1682. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||