Hein J. Verberne

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.

ASNC imaging guidelines for SPECT nuclear cardiology procedures: Stress, protocols, and tracers

1. Treadmill exercise is the most widely used stress modality. Several treadmill exercise protocols are described which differ in the speed and grade of treadmill inclination and may be more appropriate for specific patient populations. The Bruce and modified Bruce protocosls are the most widely used exercise protocols. 2. Upright bicycle exercise is commonly used in Europe. This is preferable if dynamic first-pass imaging is planned during exercise. Supine or semisupine exercise is relatively suboptimal and should only be used while performing exercise radionuclide angiocardiography.

I-123-mIBG myocardial imaging for assessment of risk for a major cardiac event in heart failure patients: insights from a retrospective European multicenter study

PurposeSingle-center experiences have shown that myocardial meta-iodobenzylguanidine (mIBG) uptake has prognostic value in heart failure (HF) patients. To verify these observations using a rigorous clinical trial methodology, a retrospective review and prospective quantitative reanalysis was performed on a series of cardiac 123I-mIBG scans acquired during a 10-year period at six centers in Europe.Methods123I-mIBG scans obtained on 290 HF patients [(262 with left ventricular ejection fraction (LVEF) < 50%)] from 1993 to 2002 were reanalyzed using a standardized methodology to determine the heart-to-mediastinum ratio (H/M) on delayed planar images. All image results were verified by three independent reviewers. Major cardiac events [MCEs; cardiac death, cardiac transplant, potentially fatal arrhythmia (including implantable cardioverter-defibrillator discharge)] during 24-month follow-up were confirmed by an adjudication committee.ResultsMCEs occurred in 67 patients (26%): mean H/M ratio was 1.51 ± 0.30 for the MCE group and 1.97 ± 0.54 for the non-MCE group (p < 0.001). Two-year event-free survival using an optimum H/M ratio threshold of 1.75 was 62% for H/M ratio less than 1.75, 95% for H/M ratio greater than or equal to 1.75 (p < 0.0001). Logistic regression showed H/M ratio and LVEF as the only significant predictors of MCE. Using the lower and upper H/M quartiles of 1.45 and 2.17 as high- and very low-risk thresholds, 2-year event-free survival rates were 52% and 98%, respectively. Among patients with LVEF ≤ 35% and H/M ≥ 1.75 (n = 73), there were nine MCEs because of progressive HF and only one because of an arrhythmia.ConclusionApplication of a clinical trial methodology via the retrospective reanalysis of 123I-mIBG images confirms the previously reported prognostic value of this method in HF patients, including potential identification of a quantitative threshold for low risk for cardiac mortality and potentially fatal ventricular arrhythmias.

Fractional flow reserve, absolute and relative coronary blood flow velocity reserve in relation to the results of technetium-99m sestamibi single-photon emission computed tomography in patients with two-vessel coronary artery disease.

OBJECTIVES We sought to perform a direct comparison between perfusion scintigraphic results and intracoronary-derived hemodynamic variables (fractional flow reserve [FFR]; absolute and relative coronary flow velocity reserve [CFVR and rCFVR, respectively]) in patients with two-vessel disease. BACKGROUND There is limited information on the diagnostic accuracy of intracoronary-derived variables (CFVR, FFR and rCFVR) in patients with multivessel disease. METHODS Dipyridamole technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT) was performed in 127 patients. The presence of reversible perfusion defects in the region of interest was determined. Within one week, angiography was performed; CFVR, rCFVR and FFR were determined in 161 coronary lesions after intracoronary administration of adenosine. The predictive value for the presence of reversible perfusion defects on MIBI SPECT of CFVR, rCFVR and FFR was evaluated by the area under the curve (AUC) of the receiver operating characteristics curves. RESULTS The mean percentage diameter stenosis was 57% (range 35% to 85%), as measured by quantitative coronary angiography. Using per-patient analysis, the AUCs for CFVR (0.70 +/- 0.052), rCFVR (0.72 +/- 0.051) and FFR (0.76 +/- 0.050) were not significantly different (p = NS). The percentages of agreement with the results of MIBI SPECT were 76%, 78% and 77% for CFVR, rCFVR and FFR, respectively. Per-lesion analysis, using all 161 measured lesions, yielded similar results. CONCLUSIONS The diagnostic accuracy of three intracoronary-derived hemodynamic variables, as compared with the results of perfusion scintigraphy, is similar in patients with two-vessel coronary artery disease. Cut-offvalues of 2.0 for CFVR, 0.65 for rCFVR and 0.75 for FFR can be used for clinical decision-making in this patient cohort. Discordant results were obtained in 23% of the cases that require prospective evaluation for appropriate patient management.

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.

EANM procedural guidelines for radionuclide myocardial perfusion imaging with SPECT and SPECT/CT : 2015 revision

Since the publication of the European Association of Nuclear Medicine (EANM) procedural guidelines for radionuclide myocardial perfusion imaging (MPI) in 2005, many small and some larger steps of progress have been made, improving MPI procedures. In this paper, the major changes from the updated 2015 procedural guidelines are highlighted, focusing on the important changes related to new instrumentation with improved image information and the possibility to reduce radiation exposure, which is further discussed in relation to the recent developments of new International Commission on Radiological Protection (ICRP) models. Introduction of the selective coronary vasodilator regadenoson and the use of coronary CT-contrast agents for hybrid imaging with SPECT/CT angiography are other important areas for nuclear cardiology that were not included in the previous guidelines. A large number of minor changes have been described in more detail in the fully revised version available at the EANM home page: http://eanm.org/publications/guidelines/2015_07_EANM_FINAL_myocardial_perfusion_guideline.pdf.

Prognostic value of coronary blood flow velocity and myocardial perfusion in intermediate coronary Narrowings and multivessel disease

OBJECTIVES This study aimed to investigate the roles of intracoronary derived coronary flow velocity reserve (CFVR) and myocardial perfusion scintigraphy (single photon emission computed tomography, or SPECT) for management of an intermediate lesion in patients with multivessel coronary artery disease. BACKGROUND Evaluation of the functional significance of intermediate coronary narrowings (40% to 70% diameter stenosis) is important for clinical decision making and risk stratification. METHODS In a prospective, multicenter study, SPECT was performed in 191 patients with stable angina and multivessel disease and scheduled for angioplasty (percutaneous transluminal coronary angioplasty, or PTCA) of a severe coronary narrowing. Coronary flow velocity reserve was determined selectively distal to an intermediate lesion in another artery using a Doppler guidewire. Percutaneous transluminal coronary angioplasty of the intermediate lesion was deferred when SPECT was negative or CFVR greater-than-or-equal 2.0. Patients were followed for one year to document major cardiac events (death, infarction, revascularization), related to the intermediate lesion. RESULTS Reversible perfusion defects were documented in the area of the intermediate lesion in 30 (16%) patients; CFVR was positive in 46 (24%) patients. Percutaneous transluminal coronary angioplasty of the intermediate lesion was deferred in 182 patients. During follow-up, 19 events occurred (3 myocardial infarctions, 16 revascularizations). Coronary flow velocity reserve was a more accurate predictor of cardiac events than was SPECT; relative risk: CFVR 3.9 (1.7 to 9.1), p < 0.05; SPECT 0.5 (0.1 to 3.2), p = NS. Multivariate analysis revealed CFVR as the only significant predictor for cardiac events. CONCLUSIONS Deferral of PTCA of intermediate lesions in multivessel disease is safe when CFVR greater-than-or-equal 2.0 (event rate 6%). This selective evaluation of coronary lesion severity during cardiac catheterization allows a more accurate risk stratification than does SPECT, which is important for clinical decision making in this patient cohort.

How to use myocardial 123I-MIBG scintigraphy in chronic heart failure

Cardiac sympathetic neuronal function and activity can be assessed noninvasively by the use of I-metaiodobenzylguanidine (I-MIBG), an analogue of norepinephrine [1]. In the past two decades, a large number of investigators have demonstrated decreased myocardial I-MIBG uptake in patients with chronic heart failure (CHF) and have shown that those with the lowest uptake tend to have the poorest prognosis [2–12]. There have also been findings suggesting that abnormalities of myocardial I-MIBG uptake may be predictive of increased risk of ventricular arrhythmia and sudden cardiac death [13, 14]. One factor that has constrained acceptance of cardiac I-MIBG imaging as a clinical management tool in heart failure has been the variability of the technical aspects of the procedure. Although most reports include the heart-to-mediastinum (H/M) ratio as the measure of myocardial uptake, the methods used to obtain this parameter have shown considerable variation. However, the influence of procedural and acquisition parameters on the reproducibility of this measurement technique have only occasionally been considered.

Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans

Background: Elevated lipoprotein(a) [Lp(a)] is a prevalent, independent cardiovascular risk factor, but the underlying mechanisms responsible for its pathogenicity are poorly defined. Because Lp(a) is the prominent carrier of proinflammatory oxidized phospholipids (OxPLs), part of its atherothrombosis might be mediated through this pathway. Methods: In vivo imaging techniques including magnetic resonance imaging, 18F-fluorodeoxyglucose uptake positron emission tomography/computed tomography and single-photon emission computed tomography/computed tomography were used to measure subsequently atherosclerotic burden, arterial wall inflammation, and monocyte trafficking to the arterial wall. Ex vivo analysis of monocytes was performed with fluorescence-activated cell sorter analysis, inflammatory stimulation assays, and transendothelial migration assays. In vitro studies of the pathophysiology of Lp(a) on monocytes were performed with an in vitro model for trained immunity. Results: We show that subjects with elevated Lp(a) (108 mg/dL [50–195 mg/dL]; n=30) have increased arterial inflammation and enhanced peripheral blood mononuclear cells trafficking to the arterial wall compared with subjects with normal Lp(a) (7 mg/dL [2–28 mg/dL]; n=30). In addition, monocytes isolated from subjects with elevated Lp(a) remain in a long-lasting primed state, as evidenced by an increased capacity to transmigrate and produce proinflammatory cytokines on stimulation (n=15). In vitro studies show that Lp(a) contains OxPL and augments the proinflammatory response in monocytes derived from healthy control subjects (n=6). This effect was markedly attenuated by inactivating OxPL on Lp(a) or removing OxPL on apolipoprotein(a). Conclusions: These findings demonstrate that Lp(a) induces monocyte trafficking to the arterial wall and mediates proinflammatory responses through its OxPL content. These findings provide a novel mechanism by which Lp(a) mediates cardiovascular disease. Clinical Trial Registration: URL: http://www.trialregister.nl. Unique identifier: NTR5006 (VIPER Study).