G. Aernout Somsen

Prognostic value of myocardial 123I-metaiodobenzylguanidine (MIBG) parameters in patients with heart failure: a systematic review

AIMS To derive a more precise estimate of the prognostic significance of myocardial 123I-metaiodobenzylguanidine (MIBG) parameters [early heart mediastinal ratio (H/M), late H/M, and myocardial washout] in heart failure (HF). METHODS AND RESULTS Eighteen studies with a total of 1755 patients, stratifying survival, and cardiac events in patients with HF by MIBG, were eligible for analysis. The pooled hazard ratio (HR) estimates for cardiac death and cardiac events associated with washout showed no significant heterogeneity and were 1.72 [95%CI (confidence interval), 1.72-2.52; P = 0.006] and 1.08 (95%CI: 1.03-1.12; P < 0.001), respectively. The pooled HR estimates for cardiac death and cardiac events associated with early H/M and late H/M showed significant heterogeneity (I2 > or = 75%). Limiting the pooling to the qualitative best three studies rendered I2 insignificant (I2 = 0) and resulted in a pooled HR of late H/M for cardiac death of 1.82 (95%CI: 0.80-4.12; P = 0.15) and for cardiac events of 1.98 (95%CI: 1.57-2.50; P < 0.001). CONCLUSION Our results indicate that patients with HF and decreased late H/M or increased myocardial MIBG washout have a worse prognosis compared with those with normal semi-quantitative myocardial MIBG parameters.

Proposal for standardization of 123I-metaiodobenzylguanidine (MIBG) cardiac sympathetic imaging by the EANM Cardiovascular Committee and the European Council of Nuclear Cardiology

This proposal for standardization of 123I-metaiodobenzylguanidine (iobenguane, MIBG) cardiac sympathetic imaging includes recommendations for patient information and preparation, radiopharmaceutical, injected activities and dosimetry, image acquisition, quality control, reconstruction methods, attenuation, scatter and collimator response compensation, data analysis and interpretation, reports, and image display. The recommendations are based on evidence coming from original or scientific studies whenever possible and as far as possible reflect the current state-of-the-art in cardiac MIBG imaging. The recommendations are designed to assist in the practice of performing, interpreting and reporting cardiac sympathetic imaging. The proposed standardization does not include clinical indications, benefits or drawbacks of cardiac sympathetic imaging, and does not address cost benefits or cost effectiveness; however, clinical settings of potential utility are mentioned. Standardization of MIBG cardiac sympathetic imaging should contribute to increasing its clinical applicability and integration into current nuclear cardiology practice.

Influence of collimator choice and simulated clinical conditions on 123I-MIBG heart/mediastinum ratios: a phantom study.

Purpose123I presents imaging problems owing to high-energy photon emission. We investigated the influence of collimators on 123I-MIBG heart/mediastinum ratios (H/M ratios). Secondly, we assessed the influence on H/M ratios of different activity concentrations, simulating clinical conditions. Thirdly, the value of scatter correction was assessed.MethodsThe AGATE cardiac phantom was filled with 123I in three sequential conditions: A, heart and mediastinal activity; B, adding lung activity; and C, adding liver activity (protocol I). In protocol II, myocardium and liver were filled with different activities ranging from low to high. For each condition, static anterior planar and single-photon emission computed tomography studies were acquired on a Siemens e.cam (SI) and a General Electric Millennium VG (GE) system, using low-energy high-resolution and medium-energy (ME) collimators for protocol I and only ME collimators for protocol II . For the SI camera, a triple energy window (TEW) scatter correction was applied.Results Planar H/M ratios were influenced by scatter and septal penetration from increasing amounts of liver activity. These effects were less pronounced for ME collimators. Although the TEW scatter correction increased ratios overall, TEW correction did not improve the relative differences between the ratios. TEW correction therefore does not add any benefit to obtain an accurate reflection of myocardial activity concentrations.Conclusion For straightforward implementation of semi-quantitative 123I-MIBG myocardial studies, we recommend the use of ME collimators without scatter correction.

For what endpoint does myocardial 123I-MIBG scintigraphy have the greatest prognostic value in patients with chronic heart failure? Results of a pooled individual patient data meta-analysis

AIMS The purpose of this study was to determine the most appropriate prognostic endpoint for myocardial (123)I-metaiodobenzylguanidine (MIBG) scintigraphy in patients with chronic heart failure (CHF) based on aggregate results from multiple studies published in the past decade. METHODS AND RESULTS Original individual late (3-5 h) heart/mediastinum (H/M) ratio data of 636 CHF patients were retrieved from six studies from Europe and the USA. All-cause mortality, cardiac mortality, arrhythmic events, and heart transplantation were investigated to determine which provided the strongest prognostic significance for the MIBG imaging data. The majority of patients was male (78%), had a decreased left ventricular ejection fraction (31.1 ± 12.5%), and a mean late H/M of 1.67 ± 0.47. During follow-up (mean 36.9 ± 20.1 months), there were 83 deaths, 67 cardiac deaths, 33 arrhythmic events, and 56 heart transplants. In univariate regression analysis, late H/M was a significant predictor of all event categories, but lowest hazard ratios (HRs) were for the composite endpoint of any event (HR = 0.30, 95% CI 0.19-0.46), all-cause (HR = 0.29, 95% CI 0.16-0.53), and cardiac mortality (HR = 0.28, 95% CI 0.14-0.55). In multivariate analysis, late H/M was an independent predictor for all event categories, except for arrhythmias. CONCLUSIONS This pooled individual patient data meta-analysis showed that, in CHF patients, the late H/M ratio is not only useful as a dichotomous predictor of events (high vs. low risk), but also has prognostic implication over the full range of the outcome value for all event categories except arrhythmias.

Stress-related variations in left ventricular function as assessed with gated myocardial perfusion SPECT

BackgroundThere is inconsistency in reported patient characteristics associated with differences in basal and poststress left ventricular function (delta ejection fraction [△EF]) assessed by gated single photon emission computed tomography (SPECT). This inconsistency may therefore hamper adequate interpretation. In this study we first determined the reproducibility of serial gated SPECT-assessed left ventricular function. Second, we determined whether left ventricular ejection fraction (LVEF) assessed directly after stress reflects basal LVEF and, if not, what patient characteristics were associated with this discrepancy in LVEF.>/<Methods and ResultsSerial reproducibility of technetium 99m tetrofosmin gated SPECT-assessed LVEF in 22 patients showed a mean difference between two sequential measurements at rest of 0.09% EF units, with a 95% limit of agreement (2 SDs) at 5.8% EF units. In 229 patients Tc-99m tetrofosmin gated SPECT was performed after stress and at rest. Independent predictors of △EF were the presence of scintigraphically proven ischemia (standardized coefficient, -1.256; P = .003) and difference in heart rate at the time of acquisition (standardized coefficient, 0.121; P = .001).>/<ConclusionsGated SPECT-assessed LVEF at rest is reproducible under standard clinical conditions. However, LVEF assessed after stress does not represent LVEF at rest in patients with scintigraphically proven ischemia and in patients with increased heart rate after stress compared with heart rate at rest.>/<

Impact of mediastinal, liver and lung (123)I-metaiodobenzylguanidine ( (123)I-MIBG) washout on calculated (123)I-MIBG myocardial washout.

PurposeIn planar 123I-metaiodobenzylguanidine (123I-MIBG) myocardial imaging mediastinum (M) activity is often used as a background correction in calculating “washout” (WO). However, the most likely sources for counts that might produce errors in estimating myocardial (Myo) activity are lung (Lu) and liver (Li), which typically have higher counts/pixel (cpp) than M. The present study investigated the relationship between changes in Lu, Li and Myo activity between early and late planar 123I-MIBG images, with comparison to M as the best estimator of non-specific background activity.MethodsStudies on 98 subjects with both early (e) and late (l) planar 123I-MIBG images were analysed. There were 68 subjects with chronic heart failure (CHF), 14 with hypertension (HTN) but no known heart disease and 16 controls (C). For each image, regions of interest (ROIs) were drawn: an irregular whole Myo, Lu, upper M and Li. For each ROI, WO was calculated as [(cpp(e)-cpp(l:decay corrected))/cpp(e)]×100%.Results Multivariable forward stepwise regression analysis showed that overall a significant proportion of the variation in Myo WO could be explained by a model containing M WO and Lu WO (37%, p < 0.001). Only in controls was M WO the sole variable explaining a significant proportion of the variation in Myo WO (27%, p = 0.023).ConclusionAlthough increased Myo WO in CHF subjects reflects disease severity, part of the count differences measured on planar 123I-MIBG myocardial images likely reflects changes in the adjacent and surrounding Lu tissue. The results for the controls suggest that this is the only group where a mediastinum correction alone may be appropriate for cardiac WO calculations.

Comparison between iodine 123 metaiodobenzylguanidine scintigraphy and heart rate variability for the assessment of cardiac sympathetic activity in mild to moderate heart failure

This study demonstrates that in patients with mild to moderate heart failure, cardiac metaiodobenzylguanidine (MIBG) washout positively correlates with normalized low-frequency power in the heart rate variability spectrum. Alterations of the cardiac sympathetic nervous system could be detected with MIBG scintigraphy in patients with normal plasma norepinephrine levels. Therefore cardiac MIBG washout may be a valuable noninvasive technique to assess early alterations in cardiac sympathetic activity that may have potential clinical implications in patients with mild to moderate heart failure.

Cardiac iodine-123 metaiodobenzylguanidine uptake in animals with diabetes mellitus and/or hypertension

The aim of the present study was to evaluate the use of the noradrenaline analogue iodine-123 metaiodobenzylguanidine ([123I]MIBG) for the assessment of cardiac sympathetic activity in the presence of diabetes mellitus and/or hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an intravenous injection of streptozotocin (STZ). The other model used lean and obese Zucker rats. In all groups basic haemodynamic values were established and animals received an intravenous injection of 50 μCi [123I]MIBG. Initial myocardial uptake and washout rates of [123I]MIBG were measured scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left cardiac ventricular β-adrenoceptor density was determined. The diabetic state, both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic induction), appeared to induce a lower cardiac density of β-adrenoceptors, indicative of increased sympathetic activity. Cardiac [123I]MIBG then showed increased washouts, thereby confirming enhanced noradrenergic activity. This parallism of results led to the conclusion that [123I]MIBG wash-out measurements could provide an excellent tool to assess cardiac sympathetic activity non-invasively. However, in hypertension (WKY vs SHR), both parameters failed to show parallelism: no changes in β-adrenoceptor density were found, whereas [123I]MIBG wash-out rate was increased. Thus, either [123I]MIBG washout or ß-adrenoceptor density may not be a reliable parameter under all circumstances to detect changes in the release of noradrenaline. Changes in the initial uptake of [123I]MIBG were observed as well. This may be a good marker for the disappearance of cardiac innervation, but it seems not to be a good parameter for distinguishing between loss of sympathetic innervation and enhanced uptake of noradrenaline in pathological conditions.

A European myocardial 123I-mIBG cross-calibration phantom study

AimPlanar myocardial 123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy is a highly reproducible technique. However, differences in collimator use are one of the most important factors that cause variation among institutions and studies in heart-to-mediastinum (H/M) ratio. Therefore, standardization among various gamma camera-collimator combinations is needed. Previously, a phantom has been developed to cross-calibrate different acquisition conditions in Japan. For further cross-calibration of European myocardial 123I-mIBG imaging, the aim of this study was to collect 123I-mIBG data for H/M ratios from common European gamma camera vendors.Methods210 experiments were performed in 27 European institutions. Based on these experiments, conversion coefficients for each gamma camera-collimator combination were calculated. An averaged conversion coefficient of 0.88 was used to calculate a standardized H/M ratio.ResultsOn average, LE-collimator-derived H/M ratios were significantly lower compared to ME-collimator-derived H/M ratios. The mean conversion coefficients ranged from 0.553 to 0.605 for the LE-collimator group and from 0.824 to 0.895 for the ME-collimator group.ConclusionClinically established H/M ratios can be converted into standardized H/M ratios using cross-calibrated conversion coefficients. This standardization is important for identifying appropriate thresholds for adequate risk stratification. In addition, this cross-calibration enables comparison between different national and international data.

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.