Relationship between cardiac sympathetic function and baroreceptor sensitivity after acute myocardial infarction.

The relationship between baroreceptor sensitivity (BRS) and cardiac sympathetic nerve function after acute myocardial infarction (AMI) was investigated in 34 patients. BRS was measured during the Valsalva maneuver and cardiac sympathetic function was assessed by the washout rate (WR) of I-123 meta-iodo-benzyl guanidine (123I-MIBG) with planar image (global WR) and polar map analysis (regional WR). Gated left ventricular ejection fraction (LVEF) measured by left ventriculography as a parameter of ventricular function was measured with quantitative gated SPECT (QGS). The gated LVEF correlated with global WR (r=-0.36, p=0.034) and regional WR of normal area (r=-0.46, p=0.006), but not with BRS, although BRS correlated with global WR (r=-0.43, p=0.015) and regional WR of normal area (r=-0.72, p<0.0001). After AMI, baroreceptor function is linked to sympathetic activation, as elucidated by the regional WR of normal area, which suggests that separation of the infarcted area from the non-infarcted myocardium is necessary for evaluating sympathetic activation after AMI and that the regional kinetics of 123I-MIBG in the normal area are a more suitable marker of activated cardiac nerve function than global 123I-MIBG kinetics.     

Effect of spironolactone on cardiac sympathetic nerve activity and left ventricular remodeling in patients with dilated cardiomyopathy

OBJECTIVES: We sought to evaluate the effects of spironolactone on cardiac sympathetic nerve activity and left ventricular (LV) remodeling in patients with dilated cardiomyopathy (DCM). BACKGROUND: Aldosterone prevents the uptake of norepinephrine and promotes structural remodeling of the heart. Spironolactone, an aldosterone receptor blocker, improves LV remodeling in patients with DCM, but its influence on cardiac sympathetic nerve activity has not been determined. METHODS: We selected 30 patients with DCM who were treated with an angiotensin-converting enzyme inhibitor and a loop diuretic. Fifteen patients were assigned to receive spironolactone additionally, whereas the remaining 15 patients continued their current regimen. The delayed heart/mediastinum (H/M) count ratio, delayed total defect score (TDS), and washout rate (WR) were determined from iodine-123 ((123)I)-meta-iodobenzylguanidine (MIBG) images before and six months after treatment. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were determined by echocardiography, and New York Heart Association (NYHA) functional class was estimated.RESULTS: In the spironolactone group, the TDS decreased from 36 +/- 9 to 24 +/- 13 (p < 0.0001), the H/M ratio increased from 1.64 +/- 0.20 to 1.86 +/- 0.27 (p < 0.0001), and WR decreased from 55 +/- 12% to 41 +/- 15% (p < 0.0005). In addition, the LVEDV decreased from 187 +/- 26 to 154 +/- 41 ml (p < 0.005), and LVEF increased from 33 +/- 6% to 39 +/- 6% (p < 0.005). However, there were no significant changes in these parameters in the control group. There was a significant correlation between changes in the (123)I-MIBG findings and changes in LVEDV with spironolactone treatment (TDS: r = 0.684, p = 0.0038; H/M ratio: r = -0.878, p < 0.0001; and WR: r = 0.737, p = 0.0011). The NYHA functional class improved in both groups but showed a greater improvement in the spironolactone group than in the control group (p < 0.01). CONCLUSIONS: Spironolactone improves cardiac sympathetic nerve activity and LV remodeling in patients with DCM.     

Comparison of the prognostic value of cardiac iodine-123 metaiodobenzylguanidine imaging and heart rate variability in patients with chronic heart failure: a prospective study

OBJECTIVES: We sought to prospectively compare the prognostic value of cardiac iodine-123 (I-123) metaiodobenzylguanidine (MIBG) imaging with that of heart rate variability (HRV) in patients with mild-to-moderate chronic heart failure (HF). BACKGROUND: Cardiac I-123 MIBG imaging, which reflects cardiac adrenergic nerve activity, provides prognostic information on chronic HF patients. Reduced HRV, indicating derangement in cardiac autonomic control, was also reported to be associated with a poor prognosis in chronic HF patients. METHODS: At study entry, I-123 MIBG imaging and 24-h Holter monitoring were performed in 65 chronic HF outpatients with a radionuclide left ventricular ejection fraction <40%. The cardiac MIBG heart to mediastinum ratio (H/M) and washout rate (WR) were obtained from MIBG imaging. The time and frequency domain parameters of HRV were calculated from 24-h Holter recordings. RESULTS: At a mean follow-up of 34 +/- 19 months, WR (p < 0.0001), H/M on the delayed image (p = 0.01), and normalized very-low-frequency power (n-VLFP) (p = 0.047) showed a significant association with the cardiac events (sudden death in 3 and hospitalization for worsening chronic HF in 10 patients) on univariate analysis. Multivariate analysis revealed that WR was the only independent predictor of cardiac events, although the predictive accuracy for the combination of abnormal WR and n-VLFP significantly increased, compared with that for abnormal WR (82% vs. 66%, p < 0.05). CONCLUSIONS: Cardiac MIBG WR has a higher prognostic value than HRV parameters in patients with chronic HF. The combination of abnormal WR and n-VLFP would be useful to identify chronic HF patients at a higher risk of cardiac events.     

Evaluation of cardiac sympathetic nerve activity and left ventricular remodelling in patients with dilated cardiomyopathy on the treatment containing carvedilol.

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 (123)I-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 (123)I-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 (123)I-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 (123)I-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 (123)I-MIBG scintigraphic parameters and echocardiographic parameters were improved in the DCM patients. There was a significant correlation between the changes of (123)I-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.     

Abnormality of left ventricular sympathetic nervous function assessed by (123)I-metaiodobenzylguanidine imaging in patients with COPD

BACKGROUND: Cardiac and systemic autonomic nervous function may be impaired in patients with COPD. Few reports, however, have described sympathetic nervous function of the left ventricle (LV) in COPD patients. STUDY OBJECTIVE: To assess the LV sympathetic nervous function in patients with COPD using (123)I-metaiodobenzylguanidine (MIBG) imaging of the heart. DESIGN: Prospective comparison of (123)I-MIBG imaging results in COPD patients and normal subjects. PARTICIPANTS: Twenty-eight patients with COPD without manifest right ventricular overload and 7 volunteers without cardiopulmonary disease (control subjects). MEASUREMENTS: (123)I-MIBG imaging results and plasma norepinephrine concentration were compared between the COPD and control groups. In the COPD group, pulmonary function tests were performed and all subjects were interviewed about their symptoms. RESULTS: (123)I-MIBG uptake, assessed as the cardiac to mediastinal activity ratio in the delayed image, was significantly lower in the COPD group than in the control group (p < 0.05). (123)I-MIBG turnover, expressed as the washout rate (WR) of (123)I-MIBG from 15 to 240 min, was significantly higher in the COPD group than in the control group (p < 0.01). In the COPD group, patients with dyspnea showed lower cardiac to mediastinal activity ratios and higher WRs compared with patients who had mild dyspnea. The WR correlated negatively with the vital capacity/predicted value ratio, correlated negatively with the maximal voluntary ventilation volume/predicted value ratio, and correlated positively with the residual volume/total lung capacity ratio in the COPD group. The plasma norepinephrine concentration in COPD patients was higher than that in the control subjects. CONCLUSION: Patients with COPD have significant sympathetic nervous impairment of the LV myocardium as a result of generalized sympathetic overactivity.     

Combined therapy with carvedilol and amiodarone is more effective in improving cardiac symptoms, function, and sympathetic nerve activity in patients with dilated cardiomyopathy: comparison with carvedilol therapy alone.

BACKGROUND: Carvedilol therapy has been reported to be more effective than other beta-blockers in patients with chronic heart failure (CHF). Amiodarone is an anti-arrhythmic medicine that has also been reported to be effective in patients with CHF. But the usefulness of combined therapy with carvedilol and amiodarone has not been reported. METHODS: We compared 15 patients (M/F = 3/12, age = 57 +/- 8 y) with dilated cardiomyopathy (DCM) receiving carvedilol and amiodarone with 15 patients (M/F = 3/12, age = 61 +/- 9 y) receiving carvedilol alone. Patients were studied before and after 1 year of treatment (1Y). NYHA class and exercise capacity based on the specific-activity-scale (SAS), were assessed. Cardiac sympathetic nerve activity was estimated using total defect score (TDS), H/M ratio and washout rate (WR) of 123I-MIBG imaging. Cardiac function was evaluated using 99mTc-MIBI QGS. RESULTS: Combined therapy improved several parameters much more than carvedilol alone (p < 0.05) including delta-TDS (15.0 +/- 8.6 vs. 7.6 +/- 7.2) and delta-WR (15.9 +/- 11.0% vs. 7.3 +/- 10.0%) for 123I-MIBG imaging, delta-LVEF (26.1 +/- 11.4% vs. 15.5 +/- 13.8%), delta-end-systolic volume (100 +/- 63.8 ml vs. 58.9 +/- 47.3 ml), 1Y NYHA class (1.5 +/- 0.5 vs. 1.9 +/- 0.5), 1Y SAS (7.3 +/- 0.7 Mets vs. 6.2 +/- 1.0 Mets), and delta-SAS (3.4 +/- 0.8 Mets vs. 2.6 +/- 1.1 Mets). CONCLUSION: Combined therapy with carvedilol and amiodarone is more effective in improving cardiac symptoms, exercise capacity, cardiac function and cardiac sympathetic nerve activity in patients with DCM.     

Long-term effects of the angiotensin-converting enzyme inhibitor enalapril on chronic heart failure. Examination by 123I-MIBG imaging

To examine the long-term effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril on chronic heart failure, 10 patients (7 men and 3 women, mean age: 62 +/- 11 years) with chronic stable heart failure, classified as New York Heart Association (NYHA) functional class 2-3 for more than 3 months, and a left ventricular ejection fraction less than 45% were treated with 2.5-5.0 mg of enalapril once a day for 3-15 months (mean 7 months). The causes of heart failure were old myocardial infarction (n = 7), hypertension (n = 2), and atrial fibrillation (n = 1). Radioiodinated metaiodobenzyl guanidine (123I-MIBG) imaging, radionuclide angiography, and treadmill exercise test were performed before and after the treatment. With enalapril treatment, (1) left ventricular ejection fraction (LVEF) increased significantly from 38.3 +/- 6.9% to 47.5 +/- 14.7%; (2) sub-maximal exercise time increased significantly from 205 +/- 112 to 272 +/- 120 seconds; (3) the heart to mediastinum (H/M) ratio of 123I-MIBG increased significantly (early image: 1.99 +/- 0.38 versus 2.20 +/- 0.50; delayed image: 1.86 +/- 0.44 versus 2.09 +/- 0.51); and (4) the washout rate of 123I-MIBG decreased slightly from 29.1 +/- 9.1% to 25.4 +/- 7.0%. The improvement rate of LVEF was significantly correlated with the improvement rates of the H/M ratio and washout rate after treatment with enalapril. Thus, the long-term effects of enalapril can be observed in the cardiac sympathetic nervous system, and 123I-MIBG imaging appears to be useful for evaluating the therapeutic effects of enalapril on the cardiac sympathetic nervous system in patients with chronic heart failure.     

Increased QT dispersion does not reflect the increased regional variation of cardiac sympathetic nervous activity in hypertrophic cardiomyopathy

BACKGROUND: QT dispersion (QTD) reflects regional variation of ventricular repolarization. However, the relationship between QTD and the regional variation of cardiac sympathetic nerve activity in hypertrophic cardiomyopathy (HCM) is not yet elucidated. METHODS: Cardiac sympathetic nerve activity was evaluated in 25 patients with HCM by iodine 123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy. With planar MIBG imaging, heart and mediastinum ratios (H/M) at early (20 minutes) and delayed (3 hours) acquisition and the washout rate (WR) were calculated. Polar maps of left ventricular myocardium were divided into 20 segments. The SD of early uptake (EU-SD), delayed uptake (DU-SD), and WR (WR-SD) in 20 segments as indices of regional variation were calculated. QT intervals were corrected by use of the Bazett formula. RESULTS: Maximum QTc correlated positively with H/M early, WR, and left ventricular wall thickness (LVWT). Minimum QTc correlated positively with WR and LVWT. Corrected QTD (QTDc) correlated negatively with EU-SD, DU-SD, and WR-SD and positively with the interventricular septal thickness/posterior wall thickness ratio. Stepwise regression analysis revealed that the most powerful determinants for maximum QTc, minimum QTc, and QTDc were WR, LVWT, and EU-SD, respectively. CONCLUSIONS: QTD correlated negatively rather than positively with the regional variability index of cardiac sympathetic nerve activity. These results suggest that increased QTD in patients with HCM may not reflect increased heterogeneity of cardiac sympathetic nerve activity.     

Short cardiac iodine-123-metaiodobenzylguanidine imaging protocol in heart failure.

BACKGROUND: For assessment of cardiac sympathetic nervous activity, the conventional protocol for iodine-123-metaiodobenzylguanidine ((123)I-MIBG) imaging requires several hours. METHODS AND RESULTS: To establish whether it is possible to shorten the conventional (123)I-MIBG imaging protocol, anterior planar imaging was performed in 42 heart failure (HF) patients at 5, 15 and 180 min. The washout rate of (123)I-MIBG from 5 to 15 min (WR5-15 min) was calculated as a novel index. WR5-15 min closely correlated with the conventional washout rate and inversely correlated with the heart to mediastinum ratio. Univariate Cox analysis revealed that rapid WR5-15 min, augmented plasma B-type natriuretic peptide level, and decreased left ventricular ejection fraction (LVEF) were predictors for cardiac events. Multivariate analysis showed WR5-15 min and LVEF were independent predictors. The cardiac event rate was markedly higher (73%) in patients when both WR5-15 min and LVEF were abnormal. CONCLUSIONS: WR5-15 min obtained from anterior planar imaging is useful for evaluating the severity of HF and clinical outcome, and may shorten the cardiac (123)I-MIBG scintigraphy protocol.     

Evaluation of beta-blocker therapy in patients with dilated cardiomyopathy--Clinical meaning of iodine 123-metaiodobenzylguanidine myocardial single-photon emission computed tomography

BACKGROUND: Patients with heart failure show signs of cardiac sympathetic dysfunction such as elevation of blood norepinephrine (NE) level, as a result of reduction in the number of sympathetic nerves, decrease in myocardial NE content, accelerated NE turnover or spillover of NE, and NE reuptake disorder at sympathetic nerve endings. In dilated cardiomyopathy (DCM), iodine 123-metaiodobenzylguanidine (MIBG) used clinically as a tracer for imaging of the sympathetic function was found to be useful in evaluation of severity and prognosis. METHODS AND RESULTS: A total of 143 (123)I-MIBG myocardial single-photon emission computed tomography (SPECT) images were taken at successive intervals on 58 patients with DCM (mean age 54 +/- 11 years), as well as before and after therapy to determine the severity of DCM and the therapeutic effect of beta-blocker. Patients were divided into group A (n = 20), in which left ventricular ejection fraction (LVEF) improved by 10% or more within 6 months after the administration of beta-blocker, and group B (n = 20), in which there was less than a 10% change in LVEF. After (123)I-MIBG myocardial SPECT was taken, the washout rate for the entire left ventricle was calculated from early and delayed images. The estimations of extent score and severity score were based on the polar map prepared from short axial images taken from 17 healthy volunteers (mean age 35 +/- 5 years). There was a significant correlation between LVEF and (123)I-MIBG findings (extent score, severity score, and washout rate) obtained before and after beta-blocker therapy. After beta-blocker therapy, LVEF and (123)I-MIBG findings significantly improved in group A. On the other hand, no change occurred in (123)I-MIBG findings in group B. There was no significant difference in LVEF between group A (32.1% +/- 8.0%) and group B (29.5% +/- 7.2%). Also, there was no significant difference in the washout rate between group A (54.4% +/- 10.9%) and group B (52.9% +/- 7.2%). Comparison of (123)I-MIBG images before beta-blocker therapy of group A and group B revealed that the extent score (26.5 +/- 16.0 vs 44.5 +/- 21.1, respectively; P <.01) and the severity score (24.9 +/- 21.9 vs 58.2 +/- 35.2, respectively; P <.01) on the basis of the early (123)I-MIBG image was significantly lower for group A. CONCLUSIONS: From the above findings, patients with DCM in which (123)I-MIBG uptake is high on early images were expected to show improvement in cardiac function by beta-blocker therapy. Findings also suggested that (123)I-MIBG was useful for examining the severity of DCM, determining the applicability of beta-blocker therapy, estimating the maintenance dosage of beta-blocker, and evaluating prognosis.     

Relationship between cardiac metaiodobenzylguanidine uptake and hemodynamic, functional and neurohormonal parameters in patients with heart failure.

BACKGROUND: Sympathetic activation plays a pivotal role in heart failure attributing to the disease process and symptoms of the patient. Myocardial sympathetic activity can be visualized using radioiodinated metaiodobenzylguanidine 123I-MIBG, a structural analogue of norepinephrine (NE). AIM OF THE STUDY: We investigated whether a relation exists between myocardial MIBG uptake and different functional, hemodynamic and neurohormonal parameters in patients with chronic heart failure. METHODS AND RESULTS: The study comprised 52 patients with stable congestive heart failure functional class II or III and left ventricular ejection fractions of <35%. The heart/mediastinum ratio (H/M ratio) was calculated to quantify myocardial MIBG uptake. A significant correlation was found between peak oxygen consumption and maximal exercise duration as exercise parameters and H/M ratio of MIBG (R, respectively, 0.36 and 0.4, P<0.05). From all other measured parameters, only plasma NE showed a significant correlation with the H/M ratio of MIBG. CONCLUSION: Cardiac sympathetic activity, as measured by myocardial MIBG uptake, is correlated with peak exercise parameters.     

Effect of long-term beta-blocker therapy on microvolt-level T-wave alternans in association with the improvement of the cardiac sympathetic nervous system and systolic function in patients with non-ischemic heart disease.

The purpose of this study was to test a hypothesis that T-wave alternans (TWA) is improved in association with an improvement in cardiac sympathetic nervous system and systolic function by oral beta-blocker therapy in patients with non-ischemic heart disease (NIHD). TWA testing, (123)I-metaiodobenzylguanidine (MIBG) imaging and echocardiography were performed at the baseline and 3 months after beta-blocker therapy in 26 patients with NIHD and positive TWA. The alternans voltage (V(alt)), the heart-to mediastinal-ratio on the early (e-H/M) and delayed (d-H/M) images, the washout rate (WR), the left ventricular ejection fraction (LVEF), and the calculated rate of change by beta-blocker therapy in each parameter (ie, deltaV(alt), deltae-H/M, deltad-H/M, deltaWR and deltaLVEF) were measured. After therapy, TWA turned negative in 8 patients (group A) and remained positive in 18 (group B); V(alt) was significantly decreased in group B (p<0.001). In group A, e-H/M, d-H/M and LVEF were significantly increased (e-H/M: p<0.05, d-H/M and LVEF: p<0.01), as were e-H/M and LVEF in group B (p<0.05). There were significant correlations between deltaV(alt) and deltae-H/M (r=-0.61, p<0.01), deltad-H/M (r=-0.82, p<0.0001), deltaWR (r=0.60, p<0.01) and deltaLVEF (r=-0.70, p<0.01). In patients with NIHD, the TWA is improved in association with the improvement in cardiac sympathetic nervous system abnormalities and left ventricular systolic dysfunction by beta-blocker therapy.     

Relationship between cardiac 123I-metaiodobenzylguanidine imaging and the transcardiac gradient of neurohumoral factors in patients with dilated cardiomyopathy.

Cardiac sympathetic nervous function is altered in congestive heart failure (CHF) and the uptake and washout rate of cardiac 123I-metaiodobenzylguanidine (MIBG) are useful markers for evaluating the severity of it. To assess what parameters predict decreased uptake or increased washout rate of MIBG, the concentrations of neurohumoral factor in both the aorta (Ao) and coronary sinus (CS) were measured, as well as hemodynamic parameters by catheterization, in patients with dilated cardiomyopathy (DCM). MIBG imaging was performed within 1 week of cardiac catheterization. Regarding MIBG parameters, the correlation with the transcardiac gradient of norepinephrine (NE), brain natriuretic peptide (BNP) and hemodynamics was investigated. Stepwise multivariate regression analysis was used to determine which variables closely correlated with cardiac MIBG parameters. There was a significant increase in the NE level between the Ao (446 pg/ml) and the CS (727 pg/ml). According to stepwise multivariate regression analysis, the heart/mediastinum (H/M) ratio independently correlated with the transcardiac gradient of BNP (r=-0.480, p<0.01), and the washout rate independently correlated with the transcardiac gradient of NE (r=0.481, p<0.01). These findings indicate that the H/M ratio may reflect the transcardiac gradient of BNP, which implies the degree of left ventricular dysfunction and/or damage and the washout rate may reflect altered cardiac sympathetic nerve terminal in DCM patients with CHF, suggesting that both the H/M ratio and washout rate provide important information about the failing ventricle.     

Improvement in cardiac adrenergic function post biventricular pacing for heart failure.

AIMS: We investigated whether biventricular (BiV) pacing favourably affects cardiac sympathetic activity in heart failure (HF). METHODS AND RESULTS: In 10 HF patients treated with BiV pacing, we assessed cardiac sympathetic activity by metaiodobenzylguanidine ((123)I-MIBG) imaging. Patients were randomized in a double-blinded crossover fashion, for two weeks of either inactivation of BiV pacing or BiV pacing, with crossover to the alternate group for a further two weeks. After randomization blocks, cardiac (123)I-MIBG imaging and a 6 min walk test were performed. BiV pacing was associated with significant improvements in cardiac (123)I-MIBG uptake reflected by increases in early (BiV 1.71 +/- 0.09 vs. non-BiV 1.63 +/- 0.06, P = 0.03) and late (at 4 h) heart to mediastinal ratio of uptake (BiV 1.54 +/- 0.08 vs. non-BiV 1.45 +/- 0.06, P = 0.03). Additionally, pulmonary (123)I-MIBG uptake, measured as lung to mediastinal ratio, significantly improved (P = 0.009). Six-minute walk and systolic blood pressure tended to improve with BiV vs. non-BiV pacing (P = 0.09). CONCLUSION: In patients with stable HF, BiV pacing is associated with long-term improvements in cardiac sympathetic nerve activity, as reflected by improvements in cardiac (123)I-MIBG uptake. This is a potential mechanism for morbidity and mortality benefits observed in larger studies.     

Prediction of cardiac sympathetic nerve activity and cardiac functional outcome after treatment in patients with dilated cardiomyopathy: examination using dobutamine gated blood pool scintigraphy

OBJECTIVES: This study evaluated whether dobutamine gated blood pool scintigraphy can predict improvement of cardiac sympathetic nerve activity and cardiac function. METHODS: Sixteen patients(10 men and 6 women, mean age 59 +/- 13 years) with dilated cardiomyopathy underwent dobutamine gated blood pool scintigraphy to measure left ventricular ejection fraction (LVEF) using tracer at 0, 5, 10 and 15 micrograms/kg/min before treatment. Patients were divided into good responders (LVEF increase > or = 15%) 8 patients(GR Group) and poor responders(LVEF increase < 15%) 8 patients (PR Group) after treatment with beta-blocker or amiodarone with a background treatment of digitalis, diuretics and angiotensin converting enzyme inhibitor. I-123 metaiodobenzylguanidine(MIBG) imaging to evaluate cardiac sympathetic nerve activity and echocardiography were performed before and at one year after treatment. MIBG imaging was obtained 4 hours after tracer injection, and the heart/mediastinum count ratio(H/M ratio) calculated from the anterior planar image and the total defect score(TDS) from the single photon emission computed tomography image. LVEF and left ventricular endo-diastolic dimension (LVDd) were measured by echocardiography and New York Heart Association(NYHA) functional class was evaluated. RESULTS: The GR Group showed TDS decreased from 28 +/- 6 to 17 +/- 12(p < 0.05), H/M ratio increased from 1.79 +/- 0.26 to 2.07 +/- 0.32(p < 0.05), LVEF increased from 29 +/- 8% to 48 +/- 10%(p < 0.01), and LVDd decreased from 65 +/- 4 mm to 58 +/- 5 mm(p < 0.05). In contrast, the PR Group showed no significant changes in TDS, H/M ratio, LVEF and LVDd. NYHA functional class improved in both groups. The improvement was better in the GR Group than in the PR Group. CONCLUSIONS: Dobutamine gated blood pool scintigraphy is useful to predict the improvement of the cardiac sympathetic nerve activity and cardiac function, and symptoms after treatment in patients with dilated cardiomyopathy.     

The role of impaired sympathetic nerve function in enhancing coronary vasoconstriction in patients with hypertrophic cardiomyopathy

Coronary vasospasm and diminished coronary blood flow reserve have often been reported in patients with hypertrophic cardiomyopathy (HCM). However, the mechanism of coronary spasm in HCM is unknown. Thus, coronary endothelial function and sympathetic nerve function in 11 patients with HCM and 11 control patients matched for age and sex were examined. The diameter of the left anterior descending coronary artery was assessed by quantitative coronary angiography, and the change in coronary blood flow was estimated using an intracoronary Doppler flow wire. To assess myocardial sympathetic nerve function, metaiodobenzylguanidine images - 15 min and 180 min after the injection of (123)I-metaiodoben-zylguanidine at a dosage of 111 MBq - were obtained, and the heart to mediastinum (H/M) count ratio and the washout rate (WR) were calculated. The H/M ratio was significantly lower in patients with HCM (2.1+/-0.3) than in control patients (2.6+/-0.4) (P<0.01). In addition, the WR was higher in patients with HCM (35+/-6%) than in control patients (28+/-3%) (P<0.01). The HCM subjects with coronary spasm had lower H/M ratios and higher WRs than HCM subjects without coronary spasm (P<0.05, respectively). In conclusion, impaired sympathetic nerve function may be associated with coronary vasospasm and diminished coronary blood flow reserve in HCM.     

Effects of candesartan on cardiac sympathetic nerve activity in patients with congestive heart failure and preserved left ventricular ejection fraction

OBJECTIVES: We sought to evaluate the effects of angiotensin receptor blocker (ARB) on cardiac sympathetic nerve activity (CSNA) in patients with congestive heart failure (CHF) with a preserved left ventricular ejection fraction (LVEF). BACKGROUND: Approximately 50% of patients with CHF have preserved LVEF. It is reported that ARB therapy improves CSNA in CHF patients and reduced LVEF. However, the effect of ARB therapy on CSNA evaluated by iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) scintigraphy has not been determined in CHF patients with preserved LVEF. METHODS: We selected 50 patients with nonischemic CHF and LVEF >40% who were treated with standard therapy. Twenty-five patients were randomized to also receive candesartan, whereas the remaining 25 patients received placebo. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined by (123)I-MIBG scintigraphy before and six months after treatment. The LV end-diastolic volume and LVEF were determined by echocardiography, and the plasma brain natriuretic peptide (BNP) concentration was also measured. RESULTS: In patients receiving candesartan, (123)I-MIBG scintigraphic and echocardiographic parameters were significantly improved after treatment. In contrast, there were no significant changes in these parameters in patients receiving placebo. There was a significant correlation between the changes in (123)I-MIBG scintigraphic findings and the percent change in BNP from baseline to six months in patients receiving candesartan (TDS: r = 0.587, p < 0.005; H/M ratio: r = -0.509, p < 0.01; WR: r = 0.602, p < 0.005). CONCLUSIONS: Adding candesartan to standard therapy can improve CSNA and LV performance in CHF patients with preserved LVEF.     

Asymmetry of cardiac [123I] meta-iodobenzyl-guanidine scans in patients with ventricular tachycardia and a "clinically normal" heart.

OBJECTIVE--Patients with exercise induced ventricular tachycardia associated with a "clinically normal" heart may have an abnormality of the regional distribution of the cardiac sympathetic nerve supply. In this study the regional distribution of the myocardial nerve supply in patients with ventricular tachycardia (VT) and control subjects was examined by [123] meta-iodobenzylguanidine (MIBG) scanning. PATIENTS AND DESIGN--Eight patients with exercise induced VT and seven patients with VT unrelated to exercise with "clinically normal" hearts were studied and compared with a control group of six subjects with atrioventricular reentrant tachycardia not related to exercise and eight patients with angiographically normal left ventricular function and normal coronary anatomy who had thallium scans without evidence of ischaemia or fixed perfusion deficits. METHODS--Single photon emission computed tomography gamma scanning was performed in patients three hours after intravenous injection of MIBG. The left ventricular MIBG uptake data was processed into bull's-eye target plots. The inferior portion of the scan frequently showed artefact due to uptake of MIBG in the liver or spleen and was not used for statistical analysis. Asymmetry of uptake was defined as a ratio of uptake exceeding 1.25 in the upper quadrants (posterior (anterolateral free wall)/anterior (anteroseptal region)) of the MIBG scan. RESULTS--Patients with VT had a higher proportion of asymmetrical MIBG scans (47%) than subjects in the control groups (0%) and this was particularly obvious in the patients with exercise induced VT (62.5%). This suggests that patients with VT may have relative denervation in the septal portion of the left ventricle leading to an imbalance of the sympathetic supply to the myocardium and locally imbalanced sympathetic or parasympathetic interactions. Considerable evidence from animal experiments suggests that imbalance of the sympathetic supply to the myocardium is important in the genesis of ventricular arrhythmia. CONCLUSIONS--These results support the hypothesis that selective denervation of the human myocardium may be an important mechanism in the genesis of VT in "clinically normal" hearts.     

Action of labetalol on norepinephrine myocardial content in left ventricular hypertrophy in hypertensive patients]

The high incidence of cardiovascular morbidity and mortality in hypertensive patients with left ventricular hypertrophy shows the great interest in understanding the pathophysiology of this process. Many reports suggest the role of catecholamines in generating left ventricular hypertrophy. The aim of this study is to evaluate the effect of labetalol on myocardial norepinephrine content in hypertensive subjects with left ventricular hypertrophy by using an isotopic norepinephrine marker, the 123I-meta-iodobenzylguanidine (123I-MIBG). Eight male and female hypertensive patients with left ventricular hypertrophy were investigated after a 30 day placebo period. Resting, ambulatory and effort blood pressure was measured. Echocardiographic parameters allowed measure of left ventricular mass index according to Devereux. And we considered left ventricular hypertrophy as left ventricular mass index greater than 120 g/m2. Cardiac and mediastinal radioactivity is detected 4 h after a 4 mCi i.v. injection of 123I-MIBG and MIBG myocardial uptake is definite as the cardiac/mediastinal ratio (N : 1.78 +/- 0.19). All subjects received at the beginning of the study (D0) 2 tablets of labetalol 200 mg, increased to 4 tablets if diastolic blood pressure during follow-up remained above 95 mmHg. Patients again underwent these explorations after 3 months of treatment (D90). Labetalol decreases in considerable manner MIBG myocardial uptake as it has been shown that it decreases tissular norepinephrine content in experimental studies. Therefore, MIBG myocardial uptake seems to be a reliable tool in evaluating drugs effect on cardiac sympathetic nervous system.     

131碘-间位碘代苄胍心肌显像探测急性心肌梗死后心脏交感神经分布和活力的变化

目的通过心脏交感神经受体显像探测急性心肌梗死(AMI)后心脏交感神经的分布和活力。方法 AMI组12例,男性11例,女性1例,年龄42～68岁,平均年龄(48±9)岁。对照组6名,男性4名,女性2名,年龄40～66岁,平均年龄(47±6)岁,为健康受试者。AMI组在AMI后2周、3个月及6个月时均行~(131)碘-间位碘代苄胍(~(131I-MIBG)受体显像及~(99m)锝-甲氧基异丁基异腈(~(99m)Tc-MIBI)心肌灌注显像(MPI),对照组在1周内完成~(131)I-MIBG受体显像及~(99m)Tc-MIBI MPI。分析~(131)I-MIBG及~(99m)TC-MIBI显像相同部位心肌节段的放射性分布,并利用感兴趣区(ROI)技术测定心肌与纵隔放射性比值(H/M)及MIBG的洗脱率(WR)。结果 (1)AMI组~(131)I-MIBG显像的放射性稀疏-缺损节段数为32个,而~(99m)Tc-MIBI显像的仪为24个。(2)AMI组在AMI后2周、3个月及6个月和对照组的~(131)I-MIBG显像H/M比值为(1.45±0.20)、(1.65±0.16)、(1.70±0.17)和(2.70±0.32),WR为32%、19%、15%和9.5%。AMI组各时间点的H/M和WR与对照组比较差异均有统计学意义(均为P0.05);AMI组2周分别与3个月和6个月比较,差异均有统计学意义(均为P0.05)。结论 AMI后交感神经受损区域明显大于MPI所显示的受损区域。AMI后心肌交感神经受体下调,表现为MIBG摄取减低;体内交感神经紧张度增高,表现为MIBG滞留时间短、洗脱率高。AMI后3～6个月内交感神经有不同程度的恢复。