Predictors of improvement in left ventricular ejection fraction with carvedilol for congestive heart failure

BACKGROUND: Beta-blocker therapy has been reported to improve survival and left ventricular ejection fraction (LVEF) in the setting of congestive heart failure (CHF). The magnitude and predictors of improved LVEF are unclear. METHODS: A total of 295 patients were enrolled in the study. Inclusion criteria were LVEF <35% at baseline and symptomatic (New York Heart Association class II to IV) CHF despite treatment with at minimum an angiotensin-converting enzyme inhibitor. Carvedilol was initiated at 3.125 mg twice daily and titrated to a target dose of 25 or 50 mg twice daily, depending on the patient's weight. Paired pretreatment baseline and 9 months with treatment follow-up quantitative LVEFs (assessed by resting radionuclide ventriculograms) were obtained in 161 (55 %) of the patients. RESULTS: LVEF improved from 25% +/- 6% at baseline to 36%+/-12% at follow-up (P<.001). Mean change in LVEF (deltaLVEF) was greater for nonischemic cardiomyopathy (NICM) (+14.5+/-2 LVEF points) than ischemic cardiomyopathy (deltaLVEF +/- 7.6+/-10 EF points, P = .001). The deltaLVEF was > or =21 LVEF points in 30% of the NICM group versus 10% of the ischemic cardiomyopathy group. Conversely, the deltaLVEF was unchanged to minimally improved (< or =5 LVEF points) in 21% of the NICM group versus 52% of the ischemic cardiomyopathy group. Multivariable analysis identified NICM and recent onset of congestive heart failure as correlates of improved LVEF. CONCLUSIONS: Carvedilol significantly improved LVEF, especially in patients with NICM and those with recent onset of CHF.     

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

Background  Carvedilol treatment reduces the mortality rate in patients with congestive heart failure. It is not known whether carvedilol treatment is effective in heart failure patients with substantial cardiac sympathetic nerve dysfunction. The goal of this study was to determine the effect of chronic carvedilol treatment in patients with cardiac sympathetic nerve dysfunction of varying severity. Methods and Results  In 22 congestive heart failure patients with idiopathic cardiomyopathy, sympathetic nerve function was assessed before and after 7.2 ± 2.7 months of carvedilol treatment with the use of iodine 123 metaiodobenzylguanidine (MIBG) imaging, radionuclide ventriculography, and transmyocardial norepinephrine sampling. Patients with relatively advanced impairment of cardiac sympathetic nerve function, as manifested by a baseline I-123 MIBG ratio lower than 1.40, had a statistically significant improvement in I-123 heartmediastinum ratio with carvedilol treatment, from 1.26 ± 0.12 to 1.39 ± 0.20 (P = .004). Of 10 patients with a baseline I-123 MIBG ratio lower than 1.40, 9 had an increase in the heart-mediastinum ratio with carvedilol treatment. Left ventricular ejection fraction increased from 25.4% ± 7.8% to 37.3% ± 14.7% (P <.001), with no difference between patients with relatively advanced versus relatively preserved cardiac sympathetic nerve function. Conclusions  Most patients with congestive heart failure show a favorable response in left ventricular function to carvedilol treatment, regardless of the baseline level of cardiac sympathetic nervous system function, as assessed by neuronal imaging with I-123 MIBG. Patients with relatively advanced impairment of baseline I-123 MIBG uptake are most likely to show evidence of improved cardiac sympathetic nervous system function in response to carvedilol therapy.(J Nucl Cardiol 2002;9:608-15.) Sponsored in part by the American Heart Association-Ohio Valley Affiliate (SW-97-12-S), the National Institutes of Health (SCOR No. 93-07-26-01), and the John R. Strauss Fund for Research and Education in Cardiac Imaging.     

I-123 MIBG imaging and heart rate variability analysis to predict the need for an implantable cardioverter defibrillator

BACKGROUND: Iodine 123 metaiodobenzylguanidine (MIBG) imaging and heart rate variability (HRV) analysis were compared in patients with an implantable cardioverter defibrillator (ICD) who did and did not receive defibrillator discharges. Although the ICD has been shown to abort potentially fatal ventricular arrhythmias, identification of patients who most benefit from this device remains difficult. As the autonomic nervous system has been implicated in the genesis of these arrhythmias, we undertook a pilot study to evaluate local myocardial sympathetic innervation with the use of I-123 MIBG myocardial imaging, as well as central autonomic tone with the use of HRV, in patients with implantable defibrillators. Test results were correlated with the occurrence of ICD discharges. METHODS AND RESULTS: Seventeen patients with previously implanted defibrillators were studied. Of these, 10 had at least 1 appropriate device discharge for ventricular tachyarrhythmias, whereas 7 had no discharge. Patients with a discharge had a significantly lower I-123 MIBG heart-mediastinal tracer uptake ratio, higher I-123 MIBG defect scores, more extensive sympathetic denervation, and significantly reduced values for several HRV parameters, particularly those in the frequency domain. When combined, the I-123 MIBG heart-mediastinal ratio and HRV 5-minute low-frequency variables were highly predictive of defibrillator discharges. All patients with a heart-mediastinal ratio lower than 1.54 and 5-minute low frequency lower than 443 ms(2) had an ICD discharge (4/4), whereas no patient with an uptake ratio greater than 1.54 and 5-minute low frequency greater than 443 ms(2) did (0/3, P =.03). CONCLUSIONS: Cardiac autonomic assessment using a combination of myocardial scintigraphic and neurophysiologic techniques may help select patients who would most benefit from an implantable defibrillator by identifying those at increased risk for potentially fatal arrhythmias.     

Quantitation of myocardial iodine-123 MIBG uptake in SPET studies: a new approach using the left ventricular cavity and a blood sample as a reference

In patients with chronic heart failure increased sympathetic activity is related to unfavourable prognosis. Since myocardial iodine-123 metaiodobenzylguanidine ([¹²³I]MIBG) uptake is related to myocardial noradrenaline content, i.e. cardiac sympathetic activity, measurement of myocardial [¹²³I]MIBG uptake may be of clinical use in determining prognosis or the effect of pharmacological intervention in these patients. The aim of the present study was to evaluate a new method to quantitate myocardial [¹²³I]MIBG uptake with respect to reproducibility and accuracy. Eighteen [¹²³I]MIBG planar and single-photon emission tomography (SPET) studies of patients with chronic heart failure were evaluated. Myocardial uptake was calculated from the myocardial (MYO) to left ventricular cavity (C) count density ratio and the¹²³I activity in a blood sample. This was performed employing planar LAO images, a single-slice SPET method using the midventricular myocardial short-axis slice, and finally a multi-slice SPET method analysing semi-automatically drawn volumes of interest (VOIs). The accuracy of the multi-slice SPET method was verified using a cardiac phantom. The planar method was found to be reproducible [intra- and interobserver coefficients of variation (IACV and IRCV) were 0.025 and 0.012 respectively] but the mean MYO/C count density ratio was only 1.31±0.16 as a consequence of overprojection. For the single-slice SPET method IACV was 0.2 and IRCV was 0.13, representing poor reproducibility. For the multi-slice SPET method IACV was 0.051, IRCV was 0.047 and the mean MYO/C count density ratio was 5.4±2.42. Accuracy was 81% at a true MYO/C count density ratio of 6 in the phantom. It is concluded that the multi-slice SPET method using the left ventricular cavity VOI and a blood sample as a reference is a reproducible and accurate method for assessing myocardial [¹²³I]MIBG uptake.     

卡维地洛与美托洛尔对充血性心力衰竭的疗效和二者的成本─效果分析

目的:观察卡维地洛与美托洛尔治疗充血性心力衰竭(CHF)的远期疗效及二者的成本─效果分析.方法:选择CHF患者114例,随机分3组.A组为对照组,予以血管扩张剂、利尿剂、地高辛、血管紧张素转换酶抑制荆等常规治疗;B组为卡维地洛组,在上述常规治疗的基础上给予卡维地洛.C组在常规治疗基础上给予美托洛尔,随访6个月.用药前后分别观察左室射血分数(LVEF)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、心衰症状等指标变化情况.结果:6个月后B组和C组LVEDD、LVESD缩小,LVEF明显提高,心衰症状明显好转.但卡维地洛组LVEF改善优于美托洛尔组:卡维地洛组的成本─效果分析低于美托洛尔组.结论:美托洛尔、卡维地洛均可逆转心室重塑,改善心脏功能.卡维地洛疗效略优于美托洛尔.     

Clinical value of lung uptake of iodine-123 metaiodobenzylguanidine (MIBG), a myocardial sympathetic nerve imaging agent, in patients with chronic heart failure

This study investigated the clinical value of I-123 MIBG pulmonary accumulation and washout in patients with chronic heart failure (CHF). Nineteen patients with CHF and 15 normal volunteers (NL) were included. The uptake ratio of heart to mediastinum (H/M), that of lung fields to mediastinum (L/M), and washout rate (WR) of the heart and lung fields were calculated in anterior planar images and compared with results of echocardiography and cardiac catheterization. In the CHF group, the lung uptake in delayed images increased and lung WR was decreased, suggesting pulmonary endothelial lesions. Furthermore, there was a negative correlation between right and left lung WR and pulmonary arterial diastolic pressure (PA(D)) and pulmonary arterial systolic pressure (PA(s)) in the CHF group. Since the WR of MIBG reflected PA, it may be used as an index of severity of cardiac dysfunction.     

Usefulness of Tc-99m methoxyisobutylisonitrile scintigraphy for evaluating congestive heart failure

BACKGROUND: Evidence is accumulating that technetium 99m methoxyisobutylisonitrile (MIBI) is not retained in the impaired myocardium. The purpose of this study was to determine whether the severity of congestive heart failure (CHF) can be evaluated by use of the washout rate (WR) of MIBI. METHODS AND RESULTS: Seventeen patients with CHF and ten healthy volunteers were enrolled in this study. MIBI and iodine 123 metaiodobenzylguanidine (MIBG) scintigraphy techniques were performed, and the WR was calculated. The blood was also sampled for the measurement of levels of brain natriuretic peptide, which is a powerful predictor of the severity of CHF. The WR of MIBI was higher in CHF patients (31.2%+/-6.3%) than in healthy volunteers (25.2%+/-4.7%) (P<.05). There were positive correlations between the WR of MIBI and brain natriuretic peptide levels (r=0.723, P<.0001) and a negative correlation between the WR of MIBI and the left ventricular ejection fraction (r=-0.545, P<.01). The WR of MIBI was correlated with that of MIBG (r=0.603, P<.01). CONCLUSIONS: MIBI scintigraphy is useful in evaluating the severity of congestive heart failure.     

Investigation of the relationship between regression of hypertensive cardiac hypertrophy and improvement of cardiac sympathetic nervous dysfunction using iodine-123 metaiodobenzylguanidine myocardial imaging

Although many theories exist on the subject, the mechanisms responsible for a reduction of hypertensive cardiac hypertrophy in response to antihypertensive therapy are still unclear. In order to investigate the relationship between regression of hypertensive cardiac hypertrophy and cardiac nervous function, we studied ten patients with untreated essential hypertension (six men and four women, 62±12 years old). Both echocardiography and iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging were performed before and after antihypertensive therapy. Left ventricular mass (LVM) was significantly reduced in conjunction with the reduction of blood pressure following treatment. MIBG myocardial images showed that the heart-to-mediastinum activity ratio (H/M) was significantly increased while the washout ratio was significantly decreased. Patients were divided into two groups according to the ratio of the LVM values before and after therapy (LVM ratio). Patients with an LVM ratio of less than 0.75 were classified as group A and those with values higher than 0.75 as group B. Neither the change in blood pressure nor the length of treatment was significantly different between these two groups. On the other hand, both the increase in H/M and the decrease in the washout ratio were significantly greater in group A than in group B. These results indicate that an improvement in cardiac sympathetic nervous function may be related to the regression of hypertensive cardiac hypertrophy. Increasing the subject base in these studies and a more precise analysis of the relevance of the data obtained from MIBG myocadial images are recommended to clarify how changes in cardiac sympathetic nervous function relate to the regression of hypertensive cardiac hypertrophy.     

Radionuclide noninvasive evaluation of heart failure beyond left ventricular function assessment

The management of patients with heart failure (HF) is challenging and requires the integration of clinical skills and accurate ancillary tests for the correct diagnosis and estimation of individual prognosis. Although the basic characterization of patients with HF is supported primarily by echocardiographic assessment of the left ventricular function, other noninvasive imaging procedures are being developed, including those involved in the processes of myocardial perfusion, metabolism, cellular injury, intersticial dysregulation, and neurohormonal receptor function. Nuclear techniques for molecular imaging of the myocardium may provide valuable insights into the pathophysiology, severity, management (medical/mechanical/surgical), response to treatment, and prognosis of HF patients. This will permit individualized management decisions and hopefully facilitate better clinical outcomes for patients with HF.     

射血分数保留的心力衰竭左心室舒张功能的影像学评价

射血分数保留的心力衰竭发病率在逐年上升。准确测量左室舒张功能有利于对该病的临床评价。目前可采用超声心动图、心脏MRI(CMRI)及其他多种检查方法评价左室舒张功能,并对舒张功能的病生理机制、舒张功能障碍分级有提示作用。其中CMRI技术的作用日益突出,包括舒张期容积-时间曲线、二尖瓣血流与肺静脉血流成像、心肌标记及其他CMRI技术。     

Activity of the uptake-1 norepinephrine transporter as measured by I-123 MIBG in heart failure patients with a loss-of-function polymorphism of the presynaptic α2C-adrenergic receptor

BACKGROUND: Patients with a deletion of 4 consecutive amino acids in the gene encoding for the alpha(2C)-adrenergic receptor (alpha(2C)Del322-325) have an increased prevalence of clinical heart failure, worse clinical status, and a lower left ventricular ejection fraction compared with patients without this deletion. We postulated that patients with the alpha(2C)Del322-325 polymorphism would have a compensatory increase in norepinephrine uptake-1 transporter activity as measured by iodine 123 metaiodobenzylguanidine (MIBG). METHODS AND RESULTS: Thirty-nine patients with heart failure related to idiopathic dilated cardiomyopathy were studied. Demographic characteristics, left ventricular ejection fraction, maximum oxygen consumption, exercise duration, and plasma norepinephrine levels did not differ between patients with the alpha(2C) receptor polymorphism (n = 9) and those without it (n = 30). Patients with the alpha(2C)Del322-325 polymorphism had significantly greater heart-to-mediastinum ratios of I-123 MIBG at 4 hours after tracer injection (1.60 +/- 0.19 vs 1.41 +/- 0.19, P =.0117) and greater background-corrected heart counts per pixel at 4 hours compared with patients without the polymorphism. CONCLUSIONS: Patients with genetic impairment of the alpha(2C)-adrenergic receptor have augmented activity of the norepinephrine uptake-1 transporter as measured by I-123 MIBG. Further studies are needed to clarify the mechanism by which uptake-1 transporter activity is increased in this setting.     

小剂量左西孟旦治疗老年重症急性左心衰竭的临床观察

 目的 通过与多巴酚丁胺比较,观察小剂量左西孟旦治疗老年重症急性左心衰竭的有效性。方法 对26例老年重症急性左心衰竭患者使用了左西孟旦,25例患者使用多巴酚丁胺作为对照组,观察用药前后生命体征、呼吸困难程度评分、LVEF、SV、BNP和生化指标。结果 两组用药前后生命体征比较,差异无统计学意义;两组用药后24 h呼吸困难程度评分降低,LVEF、SV升高、BNP浓度下降,与用药前比较有统计学差异(P＜0.05),且实验组显著优于对照组(P＜0.05);两组停药后24 h各项指标比较差异有统计学意义 (P＜0.05)。结论 对老年重症急性左心衰竭患者推荐使用小剂量左西孟旦。     

美托洛尔对难治性正常射血分数性急性左心衰患者心功能影响的临床研究

目的探讨高选择性β1-受体阻滞剂治疗射血分数正常的难治性急性左心室衰竭的可行性、安全性和有效性。方法①纳入50例发病在24h内,首次因端坐呼吸及呼吸困难突出者而诊断为急性左心衰竭,但超声检查射血分数（LVEF）≥45%;②经标准药物治疗无效或加重,NYHA分级达到Ⅳ级心功能的患者;③监测中心静脉压、血压、心率、血氧饱和度及血气分析、肺部罗音、呼吸次数、尿量,以及临床症状;④静脉推注美托洛尔5mg后,口服美托洛尔6.25～25mg,必要时4h重复给予美托洛尔12.5～25mg口服;④给药前后每4h测量中心静脉压1次;⑤治疗前床旁心脏彩超评价心功能变化;⑥停用正性肌力强心药物。结果①NYHA心功能改善≥1级者12例（24%）,改善2级者17例（34%）,改善3级者24例（48%）,无改善者3例（6%）,院内死亡2例（4%）;平均NYHA分级改善程度为2.24±0.89级,P〈0.01,有统计学意义;②在利尿、扩血管治疗基础上加用美托洛尔治疗后收缩压下降17.16±26.70mmHg,舒张压下降12.32±18.88mmHg,心率下降48.26±20.22次/min,中心静脉压（CVP）下降7.26±4.28cmH2O,P〈0.01,有统计学意义;③治疗后CVP为11.74±3.58cmH2O,与心功能改善程度的相关系数（r）=-0.389,P〈0.01;④美托洛尔的平均剂量为76.50±40.30mg/日,剂量与CVP下降程度相关（r=0.307,P=0.03）,与心率的下降显著相关（r=0.643,P=0.000）;⑤心率的下降程度与中心静脉压下降程度具有显著相关性（r=0.435,P=0.002）。结论传统方法治疗无效的射血分数正常心力衰竭患者,在接受利尿剂、扩血管药物治疗的基础上联合β受体阻滞剂美托洛尔可以显著降低血压、心率及中心静脉压水平,尤其通过降低心率使中心静脉压水平下降更有意义,从而改善心力衰竭的临床预后。     

依那普利联合卡维地洛治疗老年慢性心衰的临床观察

目的探讨依那普利联合卡维地洛在老年慢性心力衰竭患者治疗中的疗效、耐受性和安全性。方法选择老年充血性心力衰竭（CHF）患者130例,随机分为常规治疗组（对照组,28例）、依那普利与卡维地洛联合治疗组（观察组,42例）、依那普利治疗组31例和卡维地洛治疗组29例。4组治疗前和治疗6个月后,均使用超声心动图分别测定左心室舒张末期内径（LVEDD）、心输出量（CO）和左心室射血分数（LVEF）,进行疗效观察。结果治疗后4组LVEDD较治疗前显著减少（P〈0.05）,LVEF和CO较治疗前显著增高（P〈0.05）;治疗后观察组、LVEDD低于对照组（P〈0.05）,LVEF和CO较对照组显著增高（P〈0.05）。结论在常规治疗老年CHF患者的基础上,加用目标剂量的依那普利联合卡维地洛,对CHF患者安全有效,能明显改善心功能,提高左室射血分数。     

Dynamic123I-MIBG SPECT reflects sympathetic nervous integrity and predicts clinical outcome in patients with chronic heart failure

123I-metaiodobenzylguanidine (123I-MIBG) is useful for assessment of the severity and prognosis of patients with chronic heart failure (CHF). To examine 123I-MIBG kinetics in the early phase soon after tracer injection, we performed dynamic single photon emission computed tomography (SPECT) in 76 patients with CHF and 17 control subjects. The consecutive 15 images of 2 min-dynamic SPECT were acquired for 30 min after injection. From 0 to 4 min, a significant amount of radioactivity existed in the blood pool, thus we calculated washout rate of 123I-MIBG from 4 to 30 min (%WR-E). Patients were followed up with an end-point of cardiac death or re-hospitalization for 16 months (6-30 months). As the NYHA functional class advanced, %WR-E increased (control, NYHA class I, II, and III: 9 +/- 4%, 10 +/- 5%, 12 +/- 5%, and 17 +/- 5%*, respectively, *p < 0.01 vs. all other groups). Significant correlation was found between %WR-E and conventional WR from 30 min to 240 min (r = 0.606, p < 0.0001). %WR-E was positively correlated with left ventricular end-diastolic dimension (r = 0.372, p < 0.01) and was inversely correlated with left ventricular fractional shortening (r = -0.316, p < 0.02). The normal upper limit of %WR-E was defined as mean + 2SD value of 17 control subjects (17.1%). Patients with abnormally rapid %WR-E levels had a higher cardiac event rate than those with normal %WR-E levels (57% vs. 12%, p < 0.0001). These data suggest that washout rate of 123I-MIBG in the early phase from 4 min to 30 min (%WR-E) reflects cardiac sympathetic nervous integrity and is useful to evaluate the severity and prognosis of patients with CHF. The present results indicate a potential role of dynamic SPECT in shortening the 123I-MIBG imaging protocol.     

Use of left ventricular pacing in heart failure: Evaluation by gated blood pool imaging

BACKGROUND: Left ventricular (LV) pacing has been suggested to complement other forms of therapy in patients with heart failure. METHODS AND RESULTS: We investigated 17 patients (15 men, 2 women, aged 68 +/- 6 years, 10 ischemic and 7 primary dilated cardiomyopathy) with heart failure (13 were in New York Heart Association class IV and 4 in class III). One month after LV pacer implantation, 12 patients reported clinical improvement (mean class 3.7 before pacing vs 2.6 with LV pacing; P = .001). We report the results of 3 equilibrium-gated blood pool studies performed in each patient, 1 before pacing and 2 after pacer implantation (1 with pacing on, and 1 after turning off the pacer). LV pacing did not modify LV ejection fraction. Phase analysis demonstrated a significant decrease of the interventricular phase shift (delta(pi)) with LV pacing (no pacing, delta(pi) = 8.99 degrees +/- 19.05 degrees; delta7n= -0.97 degrees +/- 27.85 degrees with LV pacing). Clinical improvement was observed in patients with an initial positive delta(pi) that decreased with pacing and/or an initial LV phase standard deviation >50 degrees that decreased with pacing. CONCLUSION: LV pacing induces interventricular and intraventricular synchronization. A decrease of the interventricular phase shift seems to be the most important predictor of functional recovery for paced patients with heart failure.     

Tei指数预测慢性心力衰竭病人运动耐量的价值

目的　测量慢性心力衰竭病人的Tei指数 ,分析Tei指数与 6分钟步行距离的关系。方法　慢性心力衰竭住院病人 70例 ,行超声心动图检查 ,所有病人进行 6分钟步行试验 ,分析 6分钟步行距离与超声心动图各参数的相关性。结果　平均Tei指数随NYHA分级的增加而增加 ,单因素相关分析显示Tei指数与E/A比值呈正相关 ,与左室晚期充盈的A峰速度、E峰减速时间DT及左室射血分数呈负相关。Tei指数与心率、血压、年龄无相关性。与单纯反映左室收缩舒张功能的指标相比 ,Tei指数与 6分钟步行距离之间有更强的相关性 (r=- 0 .5 80 ,P <0 0 0 1)。多因素逐步回归分析显示Tei指数与A峰速度为预测心力衰竭病人 6分钟步行距离的独立因素。结论　左室舒张功能异常比左室收缩功能异常对慢性心力衰竭病人运动耐量的影响更明显。Tei指数反映整体的心肌功能 ,对于评价左室收缩功能不全病人的心肺运动耐量是一个很有价值、简便、易重复的指标     

Impact of exercise rehabilitation on cardiac neuronal function in heart failure: an iodine-123 metaiodobenzylguanidine scintigraphy study

Exercise training can induce important haemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examined the impact of exercise rehabilitation on cardiac neuronal function using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy. Fourteen patients (11 men, 3 women; mean age 48 years; range: 36–66 years) with stable chronic heart failure of NYHA class II–III and an initial resting radionuclide left ventricular ejection fraction (LVEF) <50% were enrolled in the study. Patients underwent progressive, supervised endurance training (treadmill test, Bruce protocol) during a 6-month period (60 sessions, 3 sessions per week) at a cardiac rehabilitation referral centre in order to measure exercise parameters. Planar ¹²³I-MIBG scintigraphy provided measurements of cardiac neuronal uptake (heart-mediastinum ratio activity, 4 h after intravenous injection of 185 MBq of MIBG). Radionuclide LVEF was also assessed at the outset and after 6 months of exercise training. Workload (801±428 vs 1229±245 kpm·min^–1, P = 0.001), exercise duration (504±190 vs 649±125 s, P = 0.02), and myocardial MIBG uptake (135%±19% vs 156%±25%, P = 0.02) increased significantly after rehabilitation. However, LVEF did not change significantly (23%±9% vs 21%±10%, p = NS). It is concluded that exercise rehabilitation induces improvement of cardiac neuronal function without having negative effects on cardiac contractility in patients with stable chronic heart failure. Received 23 September and in revised form 24 November 1997     

Comparison of [123I]metaiodobenzylguanidine kinetics with heart rate variability and plasma norepinephrine level

Background  [¹²³I]Metaiodobenzylguanidine (MIBG) imaging has been used to assess cardiac sympathetic nerve abnormalities. We evaluated the clinical significance of myocardial MIBG imaging as a measure of cardiac sympathetic nervous system function by comparing it to heart rate variability and plasma norepinephrine level. Methods and Results  In 211 subjects, we analyzed heart rate variability with 24-hour electrocardiography, performed scintigraphy with MIBG, and measured plasma norepinephrine levels. Time and frequency domain measures of heart rate variability were calculated with the Marquette heart rate variability program (Marquette Electronics, Milwaukee, Wis.). Early and late myocardial MIBG uptakes were measured at 15 and 150 minutes after injection, respectively. MIBG clearance rate from the heart and heart-to-lung and heart-to-mediastinum ratios of MIBG activities were calculated. On the whole, heart rate variability, including low-frequency power, correlated positively, but modestly so, with late MIBG uptake and negatively with MIBG clearance rate. The plasma norepinephrine level correlated negatively with late MIBG uptake and with heart rate variability, including low-frequency power, and positively with MIBG clearance rate. Similar correlations were also observed in patient subgroups with coronary artery disease, diabetes mellitus, and renal failure, but these correlations were weak (R ²<0.5). Conclusions  Increased cardiac sympathetic nervous system activity may be associated with increased myocardial MIBG clearance and decreased heart rate variability, including low-frequency power. Because these associations were not strong, however, the combination of heart rate variability with MIBG may allow an interactive assessment of the cardiac autonomic nervous system.