123I-mIBG Scintigraphy to predict risk for adverse cardiac outcomes in heart failure patients: Design of two prospective multicenter international trials

Background  ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) consists of two identical prospective open-label, multicenter, phase 3 studies (MBG311 and MBG312) evaluating the prognostic usefulness of ¹²³I-mIBG scintigraphy for identifying subjects with heart failure who will experience a major adverse cardiac event. Methods  Subjects with NYHA class II and III heart failure and left ventricular ejection fraction ≤35% were eligible for the trials. Subjects underwent planar and SPECT ¹²³I-mIBG myocardial imaging, as well as echocardiography and gated SPECT ^99mTc-tetrofosmin myocardial perfusion imaging. Subjects are then monitored on a regular basis for 2 years. Time to first occurrence of one of the following—NYHA class progression; potentially life-threatening arrhythmic event (including ICD discharge); or cardiac death, as verified by an independent adjudication panel—will be analyzed in comparison to quantitative parameters derived from ¹²³I-mIBG imaging. The primary efficacy analysis will employ the heart/mediastinum ratio on 4-hour delayed planar imaging, while secondary efficacy analyses will examine quantitative results from both planar and SPECT ¹²³I-mIBG images, as well as from ^99mTc-tetrofosmin SPECT and echocardiography. Conclusion  The results of the ADMIRE-HF trials will provide prospective validation of the potential role of ¹²³I-mIBG scintigraphy in assessing prognosis and developing management strategies for patients with heart failure. Funding Source: GE Healthcare.     

Cardiac autonomic neuropathy in patients with diabetes and no symptoms of coronary artery disease: comparison of 123I-metaiodobenzylguanidine myocardial scintigraphy and heart rate variability

Purpose

The purpose of this study was to evaluate the prevalence of cardiac autonomic neuropathy (CAN) in a cohort of patients with type 2 diabetes, truly asymptomatic for coronary artery disease (CAD), using heart rate variability (HRV) and ¹²³I-metaiodobenzylguanidine (¹²³I-mIBG) myocardial scintigraphy.

Methods

The study group comprised 88 patients with type 2 diabetes prospectively recruited from an outpatient diabetes clinic. In all patients myocardial perfusion scintigraphy, CAN by HRV and ¹²³I-mIBG myocardial scintigraphy were performed. Two or more abnormal tests were defined as CAN-positive (ECG-based CAN) and one or fewer as CAN-negative. CAN assessed by ¹²³I-mIBG scintigraphy was defined as abnormal if the heart-to-mediastinum ratio was <1.8, the washout rate was >25%, or the total defect score was >13.

Results

The prevalence of CAN in patients asymptomatic for CAD with type 2 diabetes and normal myocardial perfusion assessed by HRV and ¹²³I-mIBG scintigraphy was respectively, 27% and 58%. Furthermore, in almost half of patients with normal HRV, ¹²³I-mIBG scintigraphy showed CAN.

Conclusion

The current study revealed a high prevalence of CAN in patients with type 2 diabetes. Secondly, disagreement between HRV and ¹²³I-mIBG scintigraphy for the assessment of CAN was observed.     

Cardiac autonomic imaging with SPECT tracers

Radionuclide cardiac imaging has potential to assess underlying molecular, electrophysiologic, and pathophysiologic processes of cardiac disease. An area of current interest is cardiac autonomic innervation imaging with a radiotracer such as ¹²³I-meta-iodobenzylguanidine (¹²³I-mIBG), a norepinephrine analogue. Cardiac ¹²³I-mIBG uptake can be assessed by planar and SPECT techniques, involving determination of global uptake by a heart-to-mediastinal ratio, tracer washout between early and delayed images, and focal defects on tomographic images. Cardiac ¹²³I-mIBG findings have consistently been shown to correlate strongly with heart failure severity, pre-disposition to cardiac arrhythmias, and poor prognosis independent of conventional clinical, laboratory, and image parameters. ¹²³I-mIBG imaging promises to help monitor a patient’s clinical course and response to therapy, showing potential to help select patients for an ICD and other advanced therapies better than current methods. Autonomic imaging also appears to help diagnose ischemic heart disease and identify higher risk, as well as risk-stratify patients with diabetes. Although more investigations in larger populations are needed to strengthen prior findings and influence modifications of clinical guidelines, cardiac ¹²³I-mIBG imaging shows promise as an emerging technique for recognizing and following potentially life-threatening conditions, as well as improving our understanding of the pathophysiology of various diseases.     

Impact of age on myocardial uptake of 123I-mIBG in older adult subjects without coronary heart disease

Background

The purpose of this study was to examine the relationship between myocardial uptake of ¹²³I-mIBG and age in older normal adult subjects.

Methods

94 subjects (age 29-82, mean 58.5) without coronary heart disease were studied. All subjects underwent early and delayed planar and 4-hour SPECT ¹²³I-mIBG imaging. ¹²³I-mIBG uptake was quantified as heart/mediastinum ratio on planar images (H/M _p) and on SPECT images (H/M _s) reconstructed by filtered backprojection, ordered subsets-expectation maximization (OSEM), and OSEM with compensation for collimator septal penetration (DSP). Relationships between age and ¹²³I-mIBG uptake were examined by correlation analysis, t-tests, and analysis of variance.

Results

There was no significant correlation between age and H/M _p, reflecting comparable increases in activity in the two regions of interest with age. Results on SPECT analyses were comparable, with no significant correlation between age and H/M _s. Using DSP, ¹²³I-mIBG H/M _s was significantly higher in subjects ≥70 of age compared with younger subjects.

Conclusions

Both cardiac and background uptake of ¹²³I-mIBG increase with age in older subjects without coronary heart disease, resulting in stability of H/M results (planar and SPECT). This study suggests that prognostic analyses of quantitative ¹²³I-mIBG uptake in patients with heart disease do not require adjustment for patient age.     

Influence of myocardial region of interest definition on quantitative analysis of planar 123I-mIBG images

Purpose

In planar ¹²³I-mIBG myocardial imaging, definition of the heart region of interest (ROI) is a critical step in quantifying uptake. The present study evaluated the impact of changes in heart ROI size on quantitative results in subjects with good and poor uptake.

Methods

Reference irregular whole-heart and square upper mediastinum ROIs were defined visually on 531 planar ¹²³I-mIBG images. Based on the reference heart ROI, an automated program created two other ROIs: one larger (+1 pixel) and one smaller (?1 pixel), the stated numbers representing the spacing intervals between each epicardial boundary pixel. Two additional smaller ROIs (?2 and ?3 pixels) were drawn for the 100 images (19 %) with a heart/mediastinum (H/M) ratio ≤1.30. The number of pixels, the counts per pixel, and the H/M ratio for each heart ROI were calculated and compared to that in the reference ROI. Washout rate and changes as a function of ROI size were also calculated for 110 subjects who had both early and late images.

Results

The mean changes in heart ROI size ranged from +19.0 % for the +1 pixel to ?44.4 % for the ?3 pixels ROI. For the +1 and ?1 pixel ROIs, mean relative counts per pixel changes were ?1.2 % and +0.7 %, respectively, with corresponding ranges of change in the H/M ratio of ?0.12 to +0.05 and ?0.05 to +0.11. For scans with H/M ratio ≤1.30, mean relative counts per pixel changes were 0, 0, ?0.7 %, and ?1.4 % for the four ROIs, with range of change in the H/M ratio from ?0.13 to +0.05. Mean washout rates were almost identical for the reference ROIs (45.0 %) and the +1 pixel and ?1 pixel heart ROIs (44.9 % and 45.1 %, respectively).

Conclusion

Significant changes in the size of the best visually defined heart ROI produce minimal, clinically inconsequential changes in the H/M ratio and washout rate, even in subjects with significantly reduced myocardial uptake of ¹²³I-mIBG.     

Use of cardiac radionuclide imaging to identify patients at risk for arrhythmic sudden cardiac death

Sudden cardiac death (SCD) accounts for about ½ of all cardiovascular deaths, in most cases the result of a lethal ventricular arrhythmia. Patients considered at risk are often treated with an implantable cardiac defibrillator (ICD), but current criteria for device use, based largely on left ventricular ejection fraction (LVEF), leads to many patients receiving ICDs that they do not use, and many others not receiving ICDs but who suffer SCD. Thus, better methods of identifying patients at risk for SCD are needed, and radionuclide imaging offers much potential. Recent work has focused on imaging of cardiac autonomic innervation. ¹²³I-mIBG, a norepinephrine analog, is the tracer most studied, and a variety of positron emission tomographic tracers are also under investigation. Radionuclide autonomic imaging may identify at-risk patients with ischemic coronary artery disease, particularly following myocardial infarction and in the setting of hibernating myocardium. Most studies have been done in the setting of congestive heart failure (CHF), with a recent large multicenter study of patients with advanced disease, typically at high risk of SCD, showing that ¹²³I-mIBG can identify a low risk subgroup with an extremely low incidence of lethal ventricular arrhythmias and cardiac death, therefore, perhaps not requiring an ICD. Cardiac neuronal imaging has been shown to be better predictive of lethal arrhythmias/cardiac death than LVEF and New York Heart Association class, as well as various ECG parameters. Autonomic imaging will likely play an important role in the advancement of cardiac molecular imaging.     

Impact of aging on cardiac sympathetic innervation measured by <Superscript>123</Superscript>I-mIBG imaging in patients with systolic heart failure

Purpose

Sympathetic nervous system (SNS) hyperactivity is a salient characteristic of chronic heart failure (HF) and contributes to the progression of the disease. Iodine-123 meta-iodobenzylguanidine (¹²³I-mIBG) imaging has been successfully used to assess cardiac SNS activity in HF patients and to predict prognosis. Importantly, SNS hyperactivity characterizes also physiological ageing, and there is conflicting evidence on cardiac ¹²³I-mIBG uptake in healthy elderly subjects compared to adults. However, little data are available on the impact of ageing on cardiac sympathetic nerve activity assessed by ¹²³I-mIBG scintigraphy, in patients with HF.

Methods and results

We studied 180 HF patients (age?=?66.1?±?10.5 years [yrs]), left ventricular ejection fraction (LVEF?=?30.6?±?6.3 %) undergoing cardiac ¹²³I-mIBG imaging. Early and late heart to mediastinum (H/M) ratios and washout rate were calculated in all patients. Demographic, clinical, and echocardiographic data were also collected. Our study population consisted of 53 patients aged >75 years (age?=?77.7?±?4.0 year), 67 patients aged 62–72 years (age?=?67.9?±?3.2 years) and 60 patients aged ≤61 year (age?=?53.9?±?5.6 years). In elderly patients, both early and late H/M ratios were significantly lower compared to younger patients (p?<?0.05). By multivariate analysis, H/M ratios (both early and late) and washout rate were significantly correlated with LVEF and age.

Conclusions

Our data indicate that, in a population of HF patients, there is an independent age-related effect on cardiac SNS innervation assessed by ¹²³I-mIBG imaging. This finding suggests that cardiac ¹²³I-mIBG uptake in patients with HF might be affected by patient age.

     

The utility of ADMIRE-HF risk score in predicting serious arrhythmic events in heart failure patients: Incremental prognostic benefit of cardiac 123I-mIBG scintigraphy

Background

A minority of heart failure (HF) patients who undergo implantable cardioverter defibrillator (ICD) implantation for primary prevention of sudden cardiac death (SCD) receive device therapy. Whether the addition of mIBG scintigraphy to conventional markers of arrhythmic risk can provide incremental risk stratification in HF patients has not been investigated.

Methods

We identified 778 patients from the ADMIRE-HF study with LVEF < 35% and class II or III HF symptoms who did not have an ICD at the time of enrollment. Patients were followed up prospectively (median = 17 months) for occurrence of arrhythmic events (ArE). Heart-to-mediastinum ratio (HMR) was determined as a measure of relative myocardial sympathetic nerve activity at baseline using ¹²³I-mIBG. The primary endpoint was the first occurrence of ArE: a composite of SCD, appropriate ICD therapy, resuscitated cardiac arrest or sustained ventricular tachycardia. Multivariate regression was used to determine independent predictors of ArE and to derive a risk score for ArE prediction. The score was used to group patients according to their risk for ArE. Integrated discrimination improvement (IDI) was used to quantify improvement in risk assessment with addition of HMR.

Results

ArE occurred in 54 patients (6.9%). ArE predictors were: HMR < 1.6 (HR 3.5, 95% CI [1.52-8], P = .02), LVEF < 25% (HR 2.0, 95% CI [1.28-3.05], P = .04) and SBP < 120 (HR 1.2, 95% CI [1.03-1.39], P = .02). Event rates in the low-, intermediate-, and high risk groups were 2, 10 and 16%, respectively (P = .001). The score significantly improved risk prediction (IDI = 45%, P 0.03).

Conclusion

¹²³I-mIBG significantly provides incremental risk stratification for ArE in HF patients.     

<Superscript>123</Superscript>I-MIBG imaging can be used to evaluate microvascular disturbance caused by embolization by microdebris after rotational atherectomy

Background During rotational atherectomy (RA), the coronary atherosclerotic plaque is largely pulverized into microdebris, which may cause serious hemodynamic instability owing to significant segmental left ventricular asynergy embolization of the distal microvasculature by atheromatous debris and associated vasospasm. Objective To evaluate the usefulness of ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) in the examination of microvascular embolization after RA. Methods and results Nineteen patients with stable effort angina pectoris who had undergone RA were evaluated in this study. Left ventricular ejection fraction (LVEF) was determined by left ventriculography immediately before and after RA. The serum concentration of creatine phosphokinase (CPK), creatine phosphokinase-myocardial band (CPK-MB) isozyme, and cardiac troponin-T was determined after RA. ^99mTc-methoxyisobutylisonitrile (^99mTc-MIBI) and ¹²³I-MIBG scintigraphic examinations were also performed 1 day after RA. The regional defect score (RDS) was determined from ^99mTc-MIBI scintigraphic findings, while early and delayed RDS, heart-to-mediastinum count ratios (H/M ratios), and washout rate (WR) were determined from ¹²³I-MIBG scintigraphy. After RA, the left ventriculographic LVEF mildly decreased by ≤10% in ten patients (group A), but it decreased by >10% in the remaining nine patients (group B). There were no differences in baseline clinical characteristics between the two groups. The CPK, CPK-MB isozyme, troponin-T, RDS by ^99mTc-MIBI, H/M ratios, and WR after RA were similar in the two groups. However, the RDSs determined from early and delayed ¹²³I-MIBG in group A were significantly lower than those in group B (4.5 ± 3.8 vs. 13.4 ± 10.8, P < 0.05; 9.0 ± 6.3 vs. 17.7 ± 10.0, P < 0.05, respectively). Moreover, there were significant correlations between delta LVEF and troponin-T (r = 0.54, P < 0.05) and RDSs of early and delayed ¹²³I-MIBG (r = 0.46, P < 0.05; r = 0.64, P < 0.05, respectively). Conclusions These findings suggest that ¹²³I-MIBG imaging can be used to evaluate microvascular disturbance caused by embolization by microdebris after RA.     

Relationship between quantitative cardiac neuronal imaging with 123I-meta-iodobenzylguanidine and hospitalization in patients with heart failure

Purpose

Hospitalization in patients with systolic heart failure is associated with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged by ¹²³I-meta-iodobenzylguanidine (¹²³I-mIBG), has been associated with cardiac events in a recent multicenter study. The present analysis explored the relationship between ¹²³I-mIBG imaging findings and hospitalization.

Methods

Source documents from the ADMIRE-HF trial were reviewed to identify hospitalization events in patients with systolic heart failure following cardiac neuronal imaging using ¹²³I-mIBG. Time to hospitalization was analyzed with the Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio using multiple-failure Cox regression.

Results

During 1.4 years of median follow-up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom had H/M ratio <1.6. Among subjects hospitalized for any cause, 88 % had H/M ratio <1.6 and subjects with H/M ratio <1.6 experienced hospitalization earlier than subjects with higher H/M ratios (log-rank p?=?0.003). After adjusting for elevated brain natriuretic peptide (BNP) and time since heart failure diagnosis, a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR 1.48, 95 % CI 1.05 – 2.0; p?=?0.02).

Conclusion

The mIBG H/M ratio may risk-stratify patients with heart failure for cardiac-related hospitalization, especially when used in conjunction with BNP. Further studies are warranted to examine these relationships.     

Observer reproducibility of results from a low-dose 123I-metaiodobenzylguanidine cardiac imaging protocol in patients with heart failure

Purpose

Imaging of the cardiac autonomic system with ¹²³I-metaiodobenzylguanidine (MIBG) is useful in the evaluation of patients with a variety of cardiac conditions, including heart failure (HF), but few data are available about the reproducibility of this technique. We assessed the observer reproducibility of the results from a low-dose ¹²³I-MIBG cardiac imaging protocol in patients with HF.

Methods

A total of 74 patients (62 men, age 67?±?10 years) with HF and left ventricular systolic dysfunction (ejection fraction 31?±?7 %) underwent low-dose (111 MBq) planar and single-photon emission computed tomography (SPECT) ¹²³I-MIBG cardiac sympathetic imaging. The intraclass coefficient of correlation (ICC), Lin’s concordance correlation coefficient, and Bland-Altman analysis were used to evaluate the intraobserver and interobserver reproducibility of early and late heart-to-mediastinum (H/M) ratios and of defect scores on SPECT images. The κ statistic was used to evaluate the concordance rates for the identification of patients with a low H/M ratio (<1.60) on late planar imaging.

Results

The differences between measurements obtained twice by the same examiner and by two examiners were negligible for both early and late H/M ratios and for SPECT defect scores. These findings were confirmed by the results of Bland-Altman analysis, and ICC and Lin’s coefficient values were excellent (>0.90) for all measurements. For the identification of patients with a low H/M ratio, the κ values were 0.90 for intraobserver concordance and 0.83 for interobserver concordance.

Conclusion

The present study showed a high observer reproducibility of planar H/M ratios and SPECT defect scores using a low-dose ¹²³I-MIBG cardiac imaging protocol in patients with HF.     

Iodine-123 metaiodobenzylguanidine imaging can predict future cardiac events in Japanese patients with Parkinson’s disease

Objectives

Iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) myocardial scintigraphy provides useful diagnostic information in differentiating Parkinson’s disease (PD) from other neurological diseases. Moreover, a number of studies have reported that ¹²³I-MIBG imaging provides powerful diagnostic and prognostic information in congestive heart failure (HF) patients. The aim of the present study was to investigate the cardiovascular predictive value of cardiac ¹²³I-MIBG imaging in patients with PD.

Methods

Seventy-eight patients with PD were retrospectively studied. All patients underwent ¹²³I-MIBG imaging at 30 min (early) and 240 min (delayed) after the tracer injection, and clinical parameters were also investigated.

Results

During a mean follow-up of 27 ± 12 months, 5 patients required hospitalization for HF. There were no occurrences of myocardial infarction, fatal arrhythmia or sudden death. There was no significant coronary artery stenosis, significant valvular heart disease, or cardiomyopathy in the HF patients. The left ventricular ejection fraction (LVEF) was normal in the HF patients. ¹²³I-MIBG delayed heart to mediastinal ratio (delayed H/M) was lower and washout rate (WR) was higher in HF patients than non-HF patients (1.62 ± 0.21 vs. 1.34 ± 0.08, p = 0.019; 31.9 ± 5.5 vs. 38.2 ± 3.3, p = 0.005, respectively). Both WR and delayed H/M did not correlate with Hoehn and Yahr stage. The WR showed a weak negative correlation with delayed H/M (R = ?0.357, p < 0.001) upon simple linear regression analysis. A multivariate Cox regression analysis revealed that WR and delayed H/M were independently associated with HF (p = 0.014, p = 0.029, respectively). Kaplan–Meier analysis revealed that patients with abnormal WR (>37 %) and delayed H/M (<1.48) had a higher incidence of HF than those with normal WR and delayed H/M (p = 0.014, p = 0.04, respectively).

Conclusions

WR showed stronger predictive power than delayed H/M in Kaplan–Meier analysis. WR has more useful cardiovascular predictive value than delayed H/M in Japanese patients with PD. Further studies are needed to clarify the significance of abnormal MIBG uptake in PD patients.     

Effects of perindopril on cardiac sympathetic nerve activity in patients with congestive heart failure: comparison with enalapril

Purpose The production of aldosterone in the heart is suppressed by the angiotensin-converting enzyme (ACE) inhibitor perindopril in patients with congestive heart failure (CHF). Moreover, perindopril has been reported to have more cardioprotective effects than enalapril.Materials and methods Forty patients with CHF [left ventricular ejection fraction (LVEF) <45%; mean 33±7%] were randomly assigned to perindopril (2 mg/day; n=20) or enalapril (5 mg/day; n=20). All patients were also treated with diuretics. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS) and washout rate (WR) were determined from ¹²³I-meta-iodobenzylguanidine (MIBG) images, and plasma brain natriuretic peptide (BNP) concentrations were measured before and 6 months after treatment. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and LVEF were also determined by echocardiography.Results After treatment, in patients receiving perindopril, TDS decreased from 39±10 to 34±9 (P<0.01), H/M ratios increased from 1.62±0.27 to 1.76±0.29 (P<0.01), WR decreased from 50±14% to 42±14% (P<0.05) and plasma BNP concentrations decreased from 226±155 to 141±90 pg/ml (P<0.0005). In addition, the LVEDV decreased from 180±30 to 161±30 ml (P<0.05) and the LVESV decreased from 122±35 to 105±36 ml (P<0.05). Although the LVEF tended to increase, the change was not statistically significant (from 33±8% to 36±12%; P=NS). On the other hand, there were no significant changes in these parameters in patients receiving enalapril.Conclusion Plasma BNP concentrations, ¹²³I-MIBG scintigraphic and echocardiographic parameters improved after 6 months of perindopril treatment. These findings indicate that perindopril treatment can ameliorate the cardiac sympathetic nerve activity and the left ventricular performance in patients with CHF.     

Radionuclide imaging of cardiac autonomic innervation

Cardiac autonomic function plays a crucial role in health and disease, with abnormalities both reflecting the severity of the disease and contributing specifically to clinical deterioration and poor prognosis. Radiotracer analogs of the sympathetic mediator norepinephrine have been investigated extensively, and are at the brink of potential widespread clinical use. The most widely studied SPECT tracer, I-123 metaiodobenzylguanidine (¹²³I-mIBG) has consistently shown a strong, independent ability to risk stratify patients with advanced congestive heart failure. Increased global cardiac uptake appears to have a high negative predictive value in terms of cardiac events, especially death and arrhythmias, and therefore and may have a role in guiding therapy, particularly by helping to better select patients unresponsive to conventional medical therapies who would benefit from device therapies such as an ICD (implantable cardioverter defibrillator), CRT (cardiac resynchronization therapy), LVAD (left ventricular assist device), or cardiac transplantation. Cardiac autonomic imaging with SPECT and PET tracers also shows potential to assess patients following cardiac transplant, those with primary arrhythmic condition, coronary artery disease, diabetes mellitus, and during cardiotoxic chemotherapy. Radiotracer imaging of cardiac autonomic function allows visualization and quantitative measurements of underlying molecular aspects of cardiac disease, and should therefore provide a perspective that other cardiac tests cannot.     

Variations in 123I-metaiodobenzylguanidine (MIBG) late heart mediastinal ratios in chronic heart failure: a need for standardisation and validation

Background There is lack of validation and standardisation of acquisition parameters for myocardial ¹²³I-metaiodobenzylguanidine (MIBG). This lack of standardisation hampers large scale implementation of ¹²³I-MIBG parameters in the evaluation of patients with chronic heart failure (CHF). Methods In a retrospective multi-centre study ¹²³I-MIBG planar scintigrams obtained on 290 CHF patients (82% male; 58% dilated cardiomyopathy; New York Heart Association [NYHA classification] > I) were reanalysed to determine the late heart-to-mediastinum ratio (H/M). Results There was a large variation in acquisition parameters. Multivariate forward stepwise regression showed that a significant proportion (31%, p < 0.001) of the variation in late H/M could be explained by a model containing patient-related variables and acquisition parameters. Left ventricular ejection fraction (p < 0.001), type of collimation (p < 0.001), acquisition duration (p = 0.001), NYHA class (p = 0.028) and age (p = 0.034) were independent predictors of late H/M. Conclusions Acquisitions parameters are independent contributors to the variation of semi-quantitative measurements of cardiac ¹²³I-MIBG uptake. Improved standardisation of cardiac ¹²³I-MIBG imaging parameters would contribute to increased clinical applicability for this procedure.     

Use of <Superscript>123</Superscript>I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using ¹²³I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39±57 months, range 1–168 months) with DCM and left ventricular dysfunction underwent ¹²³I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20–75 MBq of ¹²³I-MIBG. Cardiac neuronal uptake of ¹²³I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%±49% vs 162%±26%, P<0.0001, and LVEF=43%±17% vs 26%±11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality.     

Reproducibility of planar 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy in patients with heart failure

Purpose

Despite its high prognostic value, widespread clinical implementation of ¹²³I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is hampered by a lack of validation and standardization. The purpose of this study was to assess the reliability of planar ¹²³I-MIBG myocardial scintigraphy in patients with heart failure (HF).

Methods

Planar myocardial MIBG images of 70 HF patients were analysed by two experienced and one inexperienced observer. The reproducibility of early and delayed heart-to-mediastinum (H/M) ratios, as well as washout rate (WR) calculated by two different methods, was assessed using the intraclass correlation coefficient (ICC) and the Bland-Altman analysis. In addition, a subanalysis in patients with a very low H/M ratio (delayed H/M ratio <1.4) was performed. The delayed H/M ratio was also assessed using fixed-size oval and circular cardiac regions of interest (ROI).

Results

Intra- and interobserver analyses and experienced versus inexperienced observer analysis showed excellent agreement for the measured early and delayed H/M ratios and WR on planar ¹²³I-MIBG images (the ICCs for the delayed H/M ratios were 0.98, 0.96 and 0.90, respectively). In addition, the WR without background correction resulted in higher reliability than the WR with background correction (the interobserver Bland-Altman 95?% limits of agreement were ?2.50 to 2.16 and ?10.10 to 10.14, respectively). Furthermore, the delayed H/M ratio measurements remained reliable in a subgroup of patients with a very low delayed H/M ratio (ICC 0.93 for the inter-observer analysis). Moreover, a fixed-size cardiac ROI could be used for the assessment of delayed H/M ratios, with good reliability of the measurement.

Conclusion

The present study showed a high reliability of planar ¹²³I-MIBG myocardial scintigraphy in HF patients, confirming that MIBG myocardial scintigraphy can be implemented easily for clinical risk stratification in HF.     

Cardiac resynchronization therapy evaluated by myocardial scintigraphy with <Superscript>99m</Superscript>Tc-MIBI: changes in left ventricular uptake,dyssynchrony, and function

Purpose   ^99mTc-MIBI gated myocardial scintigraphy (GMS) evaluates myocyte integrity and perfusion, left ventricular (LV) dyssynchrony and function. Cardiac resynchronization therapy (CRT) may improve the clinical symptoms of heart failure (HF), but its benefits for LV function are less pronounced. We assessed whether changes in myocardial ^99mTc-MIBI uptake after CRT are related to improvement in clinical symptoms, LV synchrony and performance, and whether GMS adds information for patient selection for CRT. Methods  A group of 30 patients with severe HF were prospectively studied before and 3 months after CRT. Variables analysed were HF functional class, QRS duration, LV ejection fraction (LVEF) by echocardiography, myocardial ^99mTc-MIBI uptake, LV end-diastolic volume (EDV) and end-systolic volume (ESV), phase analysis LV dyssynchrony indices, and regional motion by GMS. After CRT, patients were divided into two groups according to improvement in LVEF: group 1 (12 patients) with increase in LVEF of 5 or more points, and group 2 (18 patients) without a significant increase. Results  After CRT, both groups showed a significant improvement in HF functional class, reduced QRS width and increased septal wall ^99mTc-MIBI uptake. Only group 1 showed favourable changes in EDV, ESV, LV dyssynchrony indices, and regional motion. Before CRT, EDV, and ESV were lower in group 1 than in group 2. Anterior and inferior wall ^99mTc-MIBI uptakes were higher in group 1 than in group 2 (p<0.05). EDV was the only independent predictor of an increase in LVEF (p=0.01). The optimal EDV cut-off point was 315 ml (sensitivity 89%, specificity 94%). Conclusion  The evaluation of EDV by GMS added information on patient selection for CRT. After CRT, LVEF increase occurred in hearts less dilated and with more normal ^99mTc-MIBI uptake.     

Relationship between left ventricular diastolic function and myocardial sympathetic denervation measured by <Superscript>123</Superscript>I-meta-iodobenzylguanidine imaging in Anderson-Fabry disease

Purpose

Whether cardiac sympathetic nervous function abnormalities may be present in patients with Anderson-Fabry disease (AFD) remains unexplored. We investigated the relationship between left ventricular (LV) function and cardiac sympathetic nervous function in patients with AFD.

Methods

Twenty-five patients (12 men, mean age 43?±?13 years) with genetically proved AFD and preserved LV ejection fraction and ten age and gender-matched control subjects underwent speckle tracking echocardiography and ¹²³I-meta-iodobenzylguanidine (MIBG) imaging from which early and late heart to mediastinum (H/M) ratios and myocardial washout rate values were calculated.

Results

In AFD patients, a significant correlation between late H/M ratio and LV mass index (r?=??61, p?=?0.001), left atrial volume (r?=??0.72, p?<?0.001), systolic pulmonary artery pressure (r?=??0.75, p?<?0.001), and early diastolic untwisting rate (r?=??0.66, p?<?0.001) was found. Ten AFD patients exhibited a late H/M ratio below two fold standard deviation of control subjects (≤1.75). Patients showing late H/M ratio?≤?1.75 had significantly higher LV mass index, relative wall thickness, left atrial volume and systolic pulmonary artery pressure, lower systolic longitudinal strain and an early diastolic untwisting rate compared to patients with late H/M ratio?>?1.75. At multivariable linear regression analysis, early diastolic untwisting rate was the only independent predictor of late H/M ratio?≤?1.75 (odds ratio 1.15, 95 % confidence interval 1.07–1.31, p?<?0.05).

Conclusion

The present findings provide the first demonstration of a cardiac sympathetic derangement in AFD patients with preserved LV ejection fraction, which is mostly related to LV diastolic dysfunction.

     

<Superscript>123</Superscript>I-BMIPP delayed scintigraphic imaging in patients with chronic heart failure

Objective  The objective of the present study was to clarify the ability of ¹²³I-beta-methyl-iodophenylpentadecanoic acid (¹²³I-BMIPP) to evaluate the heart-to-mediastinum (H/M) ratio and myocardial global washout rate (WR) in patients with chronic heart failure (CHF). Methods  The severity of CHF was evaluated on the basis of the New York Heart Association (NYHA) classification. Twenty patients with CHF (13 with idiopathic dilated cardiomyopathy and 7 with ischemic cardiomyopathy) and 11 age-matched controls underwent myocardial radionuclide imaging. Scintigraphic images were obtained from each participant at the early (30 min following radio-isotope injection) and late (4 h) phases using ¹²³I-BMIPP. The H/M ratio and WR were calculated from planar images. Concentrations of plasma brain natriuretic peptide (BNP) were measured prior to the scintigraphic study. Results  The ¹²³I-BMIPP uptake of early H/M and global WR did not significantly differ among groups, but uptake of delayed H/M was significantly lower in patients with NYHA class III than in controls (control 2.47 ± 0.39; class III 1.78 ± 0.28, P < 0.05). The uptake of delayed H/M and global WR correlated with plasma log BNP in all participants (r = −0.38, P < 0.05; 0.43, P < 0.05, respectively). Conclusions  These data suggest that ¹²³I-BMIPP uptake of delayed H/M enhances the image of CHF severity. The myocardial WR of ¹²³I-BMIPP also effectively depicted the severity of CHF.