Metaiodobenzylguanidine Defect Research Articles

Effect of intramyocardial bone marrow-derived mononuclear cell injection on cardiac sympathetic innervation in patients with chronic myocardial ischemia

Intramyocardial bone marrow cell injection has been associated with improvements in myocardial perfusion and left ventricular function. The current substudy of a randomized, placebo-controlled, double-blinded study, investigated the effect of intramyocardial bone marrow cell injection on myocardial sympathetic innervation in patients with chronic myocardial ischemia. In a total of 16 patients (64 ± 8 years, 13 men), early and late iodine-123 metaiodobenzylguanidine (MIBG) imaging was performed before and 3 months after intramyocardial bone marrow cell injection. No improvements were observed in global early H/M ratio (P = 0.40), late H/M ratio (P = 0.43) and cardiac washout rate (P = 0.98). However, late 123-I MIBG SPECT defect score showed a trend to improvement in the bone marrow cell group (from 31.0 ± 7.1 to 28.1 ± 14.9) as compared to the placebo group (from 33.6 ± 8.5 to 34.5 ± 9.8, P = 0.055 between groups). This trend was mainly driven by a substantial improvement in three bone marrow cell-treated patients, which all had diabetes and severe MIBG defects. In these patients, the extent and severity of MIBG defects improved substantially independent of myocardial perfusion and cell injection sites. The present study does not demonstrate improvements in global cardiac sympathetic nerve innervation after intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia. However, regional analysis of sympathetic nerve innervation reveals improvements in three diabetic patients independent of myocardial perfusion, suggestive of a therapeutic effect on diabetic cardiac sympathetic dysinnervation.

Reversible reduction of cardiac sympathetic innervation after coronary artery bypass graft surgery: An observational study using serial iodine 123–labeled meta-iodobenzyl-guanidine (MIBG) imaging

Various types of surgical and interventional procedures have been reported to cause cardiac sympathetic denervation. We aimed at evaluating the effects of coronary artery bypass grafting (CABG) in cardiac sympathetic innervation through meta-iodobenzyl-guanidine (MIBG) imaging. MIBG imaging was performed in 21 patients with coronary artery disease (CAD) 1 day before and 1 week and 6 months after CABG with concomitant measurements of corrected QT interval. In each study we evaluated MIBG defect score in a 16-segment left ventricular model, MIBG-defect size (percent) from generated polar maps, and heart/mediastinum ratio. Mean MIBG defect score and size were increased (32 ± 9.5 vs 24 ± 5, P < .0001, and 49.5% ± 20.4% vs 37% ± 8.7%, P = .004, respectively) and mean heart/mediastinum ratio was reduced (1.5 ± 0.4 vs 1.9 ± 0.3, P < .0001) at 1 week after CABG. At 6 months these indices had no significant differences compared with their pre-CABG values. Mean corrected QT interval demonstrated no significant changes. Increase in MIBG score in the second imaging was associated with adverse events related to arrhythmia and myocardial dysfunction during the 6-month follow-up period in a binary logistic regression model. CABG is associated with clinically important but reversible reduction in cardiac sympathetic nerve function, with periprocedural effects (cardioplegia, hypothermia, ischemia, direct nerve injury) being possible mechanisms for this finding.

Effect of spinal cord stimulation on cardiac adrenergic nerve function in patients with cardiac syndrome X

In patients with cardiac syndrome X (CSX) who present with refractory angina episodes, spinal cord stimulation (SCS) has beneficial effects. The mechanisms of SCS, however, remain speculative. We assessed the effects of SCS on cardiac sympathetic function in these patients. We studied 11 CSX patients treated by SCS for refractory angina (mean age, 60 +/- 9 years; 5 men and 6 women), both during SCS therapy (SCS-ON) and after withdrawal of SCS therapy (SCS-OFF), using a randomized crossover design. Planar and single photon emission computed tomography iodine 123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and technetium 99m sestamibi (MIBI) bicycle exercise stress testing were performed at the end of each period. Compared with 10 healthy control subjects, CSX patients showed a lower heart-mediastinum ratio for MIBG uptake (2.19 +/- 0.3 vs 1.69 +/- 0.3, P = .001) and a higher cardiac MIBG uptake score (4.0 +/- 2.5 vs 19.7 +/- 27, P = .08). There were no differences in CSX patients during the SCS-ON and SCS-OFF phases of the study in heart-mediastinum ratio (1.74 +/- 0.3 vs 1.69 +/- 0.3, P = .13), cardiac washout rate of MIBG (42.9% +/- 14% vs 43.3% +/- 14%, P = .08), or MIBG defect score (18.7 +/- 25 vs 19.7 +/- 27, P = .22). Reversible perfusion defects during the SCS-OFF phase were detected in 8 patients; an improvement in perfusion defects was observed in 2 patients (25%) during the SCS-ON phase. Our data confirm the presence of abnormal cardiac adrenergic nerve function in CSX patients. SCS was unable to result in significant improvement of cardiac MIBG uptake abnormalities, suggesting that its therapeutic effects are unlikely to be mediated by modulation of cardiac adrenergic nerve activity.

Cardiac sympathetic nerve imaging in patients with heart failure or lethal arrhythmias: risk stratification and assessment of therapeutic interventions

Cardiac metaiodobenzylguanidine (MIBG) activity level is an independent predictor of survival and has incremental prognostic values in patients with heart failure. We prospectively compared mortality rates of 168 patients with left ventricular (LV) ejection fraction of less than 40% to clarify whether cardiac MIBG activity level was closely related to mortality rate under the treatment with angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers and whether it enables prediction of the efficacy of treatment. The drug treatment significantly reduced mortality rate at 60 months, and the reduction in mortality risk in patients without a severe MIBG defect (67%) was two-times greater than that in patients with a severe MIBG defect (32%). In other 35 patients in whom implantable cardioverter defibrillator (ICD) had been used, cardiac MIBG activity in combination with degree of heart rate variability, plasma brain natriuretic peptide (BNP) level, or ejection fraction enabled more reliable prediction of increased risk for sudden cardiac death irrespective of other clinical or electrophysiological data. Thus, cardiac MIBG activity level still has powerful prognostic power under the condition of a contemporary pharmacological treatment and is useful for appropriate selection of patients who are at greater risk for cardiac death and for prediction of the effects of aggressive therapeutic strategies.

Prognostic implications of an initial loss of cardiac metaiodobenzylguanidine uptake and diabetes mellitus in patients with left ventricular dysfunction

Background: Although altered cardiac sympathetic innervation is related to fatal outcome, the mechanisms and prognostic value of an initial cardiac metaiodobenzylguanidine (MIBG) defect are not known. Methods and Results: After quantitative cardiac MIBG imaging, 205 patients with left ventricular ejection fraction <50% were prospectively followed up with a primary end-point of cardiac death for 35 months. In regard to 38 cardiac deaths, consisting of 25 pump failure deaths, 11 sudden deaths, and 2 fatal acute myocardial infarctions, multivariate analysis identified diabetes mellitus as a significant independent predictor as well as reduced cardiac MIBG activity, use of nitrate, and New York Heart Association functional status. Independent of washout kinetics and cardiac function, patients with profound loss of initial MIBG uptake and those with late-phase MIBG activity of 1.74 or less had significantly greater mortality rates than did their counterparts. Initial cardiac MIBG activity closely correlated inversely with annual cardiac death rate. Conclusions: An initial cardiac MIBG defect and presence of diabetes mellitus indicate a low probability of long-term survival. The profound loss of initial MIBG activity is likely to be due to structural deficit of sympathetic neurons themselves, rather than accelerated sympathetic function, suggesting that denervation is one of mechanisms of cardiac sympathetic dysfunction leading to lethal clinical outcomes.

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. (J Nucl Cardiol 2003;10:121-31)

The magnitude of ST-segment elevation during catecholamine infusion correlates to I-123 metaiodobenzylguanidine defect after Q-wave myocardial infarction

The magnitude of ST-segment elevation during catecholamine infusion correlates to I-123 metaiodobenzylguanidine defect after Q-wave myocardial infarction

Abnormal cardiac adrenergic nerve function in patients with syndrome X detected by [123I]metaiodobenzylguanidine myocardial scintigraphy.

Previous studies have suggested that an abnormal cardiac adrenergic tone may have a pathophysiological role in syndrome X (effort angina, positive exercise testing, angiographically normal coronary arteries). To evaluate cardiac adrenergic nerve function, we performed [123I]metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 12 patients with syndrome X and 10 control subjects. Cardiac MIBG uptake was assessed by the heart/mediastinum (H/M) ratio and by an MIBG uptake defect score (higher values=lower uptake). In syndrome X patients, we also correlated MIBG scintigraphic findings with stress myocardial perfusion as assessed by 201Tl scintigraphy. An inferior MIBG defect was observed in only 1 control subject, whereas 9 patients (P<.01) showed MIBG defects. The heart was totally or almost totally invisible on MIBG images in 5 patients, and predominantly regional defects were observed in 4. The H/M ratio was lower (1.70+/-0.6 versus 2.2+/-0.3, P=.03) and MIBG uptake defect score higher (35+/-31 versus 4+/-2, P=.003) in syndrome X patients. Reversible stress thallium perfusion defects were found in 62% of patients with MIBG defects but in no patient with normal MIBG uptake. MIBG defects persisted unchanged in 7 patients at a 5+/-3-month follow-up study. In this study, obvious defects in global and/or regional cardiac MIBG uptake, indicating an abnormal cardiac adrenergic nerve function, were detected in 75% of patients with syndrome X. These findings strongly support the cardiac origin of chest pain in syndrome X, although the mechanisms and the pathophysiological meaning of the abnormal cardiac MIBG uptake in these patients deserve further investigation.

Cardiac sympathetic denervation in patients with coronary artery disease without previous myocardial infarction.

Myocardial infarction damages sympathetic nerve fibers coursing through the infarct zone. In this study we investigated whether coronary artery disease without myocardial infarction results in sympathetic denervation. We examined 12 patients without a history of previous myocardial infarction and 19 postinfarction patients. 1-123 metaiodobenzylguanidine (MIBG) and technetium-99m sestamibi (MIBI) single-photon emission tomography were conducted at rest to determine the extent of denervated myocardium and the extent of myocardium with reduced perfusion, respectively. In addition, myocardial perfusion during exercise was assessed with MIBI. A MIBG or MIBI defect was determined as being regional uptake of < or =30% of the maximal myocardial activity. All but 1 patient without previous infarction had MIBG defects. MIBG defects (10.3 +/- 8.5% of left ventricular mass) were significantly larger than MIBI defects at rest (2.4 +/- 3.2%, p <0.001) and during exercise (4.8 +/- 6.1%, p <0.05). In multiregression analysis, the size of an MIBG defect was associated with severity of coronary stenoses (> or =90% of lumen diameter; p <0.05), but not with age, number of significant stenoses (> or =50% of lumen diameter), left main disease, functional class, left ventricular ejection fraction, angina pectoris, maximal ST depression, or mean workload during exercise test. MIBG and MIBI defects were significantly larger in patients with severe coronary stenoses than in patients with moderate stenoses (50% to 89% of lumen diameter) (16.4 +/- 8.9% vs 6.0 +/- 5.2% [p <0.05] and 5.0 +/- 3.1% vs 0.6 +/- 1.3% [p <0.001], respectively). The size of MIBG (16.1 +/- 8.9%) and MIBI defects (7.3 +/- 6.5%) at rest in postinfarction patients did not differ from patients with severe stenoses. Our study demonstrates that cardiac adrenergic tissue is very sensitive to ischemia and that regional cardiac sympathetic denervation can occur in patients with stable coronary artery disease without previous myocardial infarction.

Iodine-123 Metaiodobenzylguanidine Cardiac Imaging to Identify and Localize Vasospastic Angina Without Significant Coronary Artery Narrowing

Objectives. We assessed the ability of iodine-123 metaiodobenzylguanidine (MIBG) imaging to identify and localize coronary spasm and determined the most useful method of MIBG analysis in vasospastic angina without significant coronary narrowing.Background. Various noninvasive methods have been used to detect vasospastic angina, but they are not very sensitive in patients with sporadic attacks. MIBG imaging has recently been proposed as a useful tool for detecting vasospastic angina.Methods. Normal limits of both visual and quantitative analysis of two-dimensional polar maps (bull’s-eyes) for MIBG imaging were at first established in 59 normal subjects. For optimal criteria of visual analysis, we established regional differences in abnormal MIBG defect scores. An abnormal region of the bull’s-eye was defined as an area >2 SD below normal. An abnormal regional washout rate was defined as <0%. Using these criteria, we prospectively evaluated 104 patients with suspected vasospastic angina. Visual, bull’s-eye and regional washout rate analyses were compared for overall detection of the disease and for individual vessel involvement.Results. Overall sensitivity by these methods was 30%, 42% and 76%, respectively. Washout rate analysis showed a significantly higher sensitivity than the other two methods. Specificity was 78%, 72% and 87%, respectively. The sensitivity of detecting spasm-induced coronary artery with washout rate analysis was 82% for the left anterior descending (LAD), 76% for the right (RCA) and 69% for the circumflex (Cx) coronary arteries. The sensitivity of visual analysis was 29%, 15% and 35%, respectively; that for bull’s-eye analysis was 34%, 54% and 41%, respectively. Washout rate analysis showed a significantly higher sensitivity for LAD spasm than for the other two methods and a higher sensitivity for RCA and Cx spasms than for visual analysis.Conclusions. Regional washout rate analysis of MIBG imaging is a highly accurate technique for determining the presence and location of coronary artery spasm.

Sympathetic reinnervation after acute myocardial infarction

Myocardial infarction produces sympathetic denervation of the necrotic myocardium and noninfarcted myocardium apical to the injury. Proof of sympathetic reinnervation after myocardial infarction has, however, remained elusive. In this study, we investigated whether cardiac sympathetic reinnervation occurs in men recovering from myocardial infarction. I-123 metaiodobenzylguanidine (MIBG), I-123 paraphenylpentadecanoic acid, and Tc-99m sestamibi scintigraphic imaging were conducted in 13 men 3 and 12 months after a first myocardial infarction to determine the extent of denervated myocardium, the size of the infarct, and the size of the myocardium with reduced perfusion, respectively. A defect was determined as regional uptake of ≤ 30% of the maximal myocardial activity. The size of the MIBG defect was not significantly different between 3 and 12 months after infarction (17 ± 8% and 18 ± 8% of left ventricular mass, respectively). There was also no significant change in the extent of viable but denervated myocardium at 3 and 12 months (average 9 ± 6% and 10 ± 5%, respectively). MIBG activity of the infarct zone (expressed as a percentage of MIBG activity of the myocardium with normal perfusion) did not change (17 ± 13% and 20 ± 16%), whereas MIBG activity of the periinfarct zone increased during follow-up (32 ± 11% and 41 ± 14%, p < 0.01). This was associated with an increase in periinfarct I-123 paraphenylpentadecanoic acid activity (40 ± 11% and 48 ± 9%, p < 0.05), but not Tc-99m sestamibi activity (48 ± 10% and 48 ± 11%). In conclusion, we did not observe sympathetic reinnervation in the infarct zone between 3 and 12 months after myocardial infarction. However, MIBG activity of the periinfarct zone increased, suggesting partial reinnervation, and this was associated with a recovery of myocardial metabolic activity of the periinfarct zone.

1009-46 Does Reinnervation of Cardiac Sympathetic Nerves Occur in Regions Denervated by Catheter Ablation of Accessory Pathways?

Long term effects of radiofrequency (RF) ablation of accessory pathways are unknown. We hypothesized that defects in sympathetic innervation detected by 1-123 metaiodobenzylguanidine (MIBG) and myocardial perfusion detected bythallium-201 (TI) scintigraphy after RF ablation would not change in three years followup. Six pts were studied 6.8 +/-9.1 days (acute) and 3.1 +/-0.3 years (chronic) after RF. TI and MIBG images were scored: absent, decreased, or normal uptake in 13 cardiac segments. The mean numbers of segments with decreased uptake of TI and MIBG were compared for acute and chronic studies. Acute Chronic TI 0.2 ± 0.4 0.7 ± 0.8 (p = NS) MIBG 1.5 ± 1.5 2.5 ± 1.5 (p = NS) As expected, MIBG defects were larger than TI defects in 9 studies. Three studies had no MIBG defects: one of these had a TI defect. There was no difference in the number of segments with decreased TI or MIBG uptake between acute and chronic studies. No segments had absent TI uptake, and only one segment had absent MIBG uptake. Two chronic MIBG defects were smaller and four larger than the acute MIBG defects. Thus, focal MIBG defects after RF ablation of accessory pathways do not significantly change in three years follow-up, suggesting sympathetic reinnervation does not occur.

Extent of cardiac autonomic denervation in relation to angina on exercise test in patients with recent acute myocardial infarction

According to the current concept, anginal pain results from stimulation of sympathetic nerves within the heart. In this study, we evaluated the role of cardiac adrenergic denervation in exercise-induced angina pectoris in 15 men with recent acute myocardial infarction. Before discharge from the hospital, the patients were subjected to a symptom-limited exercise test. Three months after the infarction, cardiac scintigraphic studies using I-123 metaiodobenzylguanidine (MIBG), I-123 paraphenylpentadecanoic acid (pPPA), and Tc-99m sestamibi (MIBI) were performed in order to determine the extent of denervated myocardium, the size of infarction, and myocardium with reduced perfusion, respectively. MIBG defect (17.2 ± 7.6% of left ventricular mass) (defect defined as an activity distribution ≤30% of the maximal myocardial activity) was larger than pPPA defect (8.3 ± 8.8%, p < 0.001) In all patients, which indicates that the area of myocardial necrosis was surrounded by viable myocardium with sympathetic denervation. The extent of viable but denervated myocardium was significantly greater in patients who developed angina pectoris than in patients without angina pectoris during the early exercise test (13.3 ± 4.4% vs 5.0 ± 2.4%, p < 0.001). In addition, patients with silent ischemia tended to have smaller areas of viable but denervated myocardium than patients with painful ischemia (5.7 ± 3.8% vs 13.8 ± 5.1%, p = 0.07). Thus, contrary to expectations, the extent of viable but denervated myocardium seems to be associated with increased pain sensitivity in patients with recent myocardial infarction.

Noradrenaline depletion in patients with coronary artery disease before and after percutaneous transluminal coronary angioplasty with iodine-123 metaiodobenzylguanidine and single-photon emission tomography

Iodine-123 metaiodobenzylguanidine (MIBG) is a noradrenaline analogue which can be used as a tracer to investigate the cardiac sympathetic nervous system. Regional ischaemia leads to noradrenaline depletion with functional denervation which can be demonstrated by reduced MIBG uptake. In order to evaluate the reversibility of ischaemia-associated damage to the sympathetic nervous system, neuronal scintigraphy with 123I-MIBG and myocardial rest and stress perfusion scintigraphy with technetium-99m sestamibi was performed in 16 patients with coronary artery disease before and 3-4 months after percutaneous transluminal coronary angioplasty (PTCA). Partial re-innervation occurred in five patients, the degree of stenosis of remaining lesions being estimated by repeat angiography to be below 40%. Unchanged MIBG defects could be confirmed in four patients with residual lesions of between 40% and 50%. Increased MIBG defects were shown in three patients with significant restenoses of more than 70%. In all patients the neuronal defects exceeded the ischaemia-induced or scar-associated perfusion defects. Three patients dropped out of this study: one for technical reasons, one due to emergency aortocoronary bypass surgery and one due to diabetic polyneuropathy. This investigation shows that the sympathetic nervous system is highly sensitive to ischaemia. Further studies need to be done to assess the conditions allowing re-innervation after PTCA.

Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction

The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic function was studied in 27 patients mean ± standard deviation 10 ± 4 days after AMI. Regional adrenergk function was evaluated noninvasively with I-123 meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four hours after its administration, there was reduced MIBG uptake in the region of infarction, 0.38 ± 0.31 counts/pixel/mCi × 103 compared with 0.60 ± 0.30 counts/pixel/mCi × 103 and 0.92 ± 0.35 counts/pixel/mCi × 103 in the zones bordering and distant from the infarct area, respectively, p < 0.001. In all patients, the area of reduced MIBG uptake after 4 hours was more extensive than the associated thallium-201 perfusion defect with defect scores of 52 ± 22 and 23 ± 18%, respectively, p < 0.001. After anterior wall AMI, the 4-hour MIBG defect score was 70 ± 13% and the degree of mismatch between myocardial perfusion and MIBG uptake was 30 ± 9% compared with 39 ± 17 and 21 ± 17% after inferior AMI, p < 0.001 and p = 0.016, respectively. The 4-hour MIBG defect score correlated inversely with the predischarge left ventricular ejection fraction, r = −0.73, p < 0.001. Patients with ventricular arrhythmia of ≥1 ventricular premature complexes per hour, paired ventricular premature complexes or ventricular tachycardia detected during the late hospital phase had higher 4-hour MIBG defect scores, 62.5 ± 15.0%, than patients with no detectable complex ventricular ectopic activity and a ventricular premature complex frequency of <1 per hour, 44.6 ± 23.4%, p = 0.036. These data suggest that after acute AMI in humans (1) the abnormality in adrenergic function is more extensive than the associated abnormality in myocardial perfusion; (2) anterior wall AMI is associated with greater disruption of cardiac adrenergic function than other infarcts; (3) the severity of cardiac adrenergic dysfunction correlates with the degree of left ventricular dysfunction; and (4) the abnormality in regional adrenergic function may be associated with the presence of ventricular ectopic activity after AMI.