Iodine-123-metaiodobenzylguanidine cardiac SPECT imaging in the qualification of heart failure patients for ICD implantation

EDITORIAL Iodine-123-metaiodobenzylguanidine cardiac SPECT imaging in the qualification of heart failure patients for ICD implantation Anna Teresińska, PhDa a The Cardinal Stefan Wyszyński Institute of Cardiology, Warsaw, Poland Received Apr 16, 2018; accepted Apr 17, 2018 doi:10.1007/s12350-018-1288-6 See related article, https://doi.org/10. 1007/s12350-018-1258-z. Heart failure (HF) is a complex clinical syndrome, with the prevalence of approximately 1-2% of the adult population in developed countries, significantly rising among elderly people.1,2 The mortality rate of patients with HF remains high despite optimal pharmacological treatment (approximately 50% within 5 years of diagnosis). Sudden cardiac death (SCD), in most cases due to ventricular arrhythmia (VA), accounts for up to 50% of deaths in HF. The risk of SCD is particularly high in patients with reduced left ventricular ejection fraction (LVEF). Implantable cardioverter defibrillators (ICDs) can abort potentially fatal VAs by way of an electrical shock or anti-tachycardia pacing. The current American College of Cardiology/American Heart Association (ACC/ AHA)1 and the European Society of Cardiology (ESC)2 guidelines, for the management of HF, recommend ICD implantation in primary prevention of SCD in symptomatic patients (NYHA Class II-III), with LVEF B 35%, [ 40 days after myocardial infarction, C 3 months on optimal medical therapy, and expected to survive substantially longer with good functional status. ICDs reduce occurrence of arrhythmic sudden deaths; however, most SCDs occur in patients who do not qualify for ICD implementation according to current criteria. On the other hand, a high percentage of patients Reprint requests: Anna Teresińska, PhD, The Cardinal Stefan Wyszyński Institute of Cardiology, Alpejska 42, 04-628 Warsaw, Poland; J Nucl Cardiol 1071-3581/$34.00 Copyright Ó 2018 The Author(s) with the device implanted on the basis of reduced LVEF and moderate symptoms never suffer an arrhythmia requiring appropriate ICD therapy. Furthermore, postprocedural complication rate accounts for up to 9% during 5.6 years (excluding a high rate of inappropriate shocks leading to worsening quality of life).3 Thus, better methods for prediction of SCD risk and qualification for ICD implantation are needed. Suitable patients to investigate are those who already have an ICD implanted - although occurrence of an appropriate ICD therapy does not necessarily mean that they would have experienced SCD if not the device, it is currently an accepted surrogate arrhythmic endpoint.4 HF is associated with activation of the sympathetic cardiac nerves. Mechanisms of cardiac arrhythmias are complex and multifactorial, but changes in cardiac adrenergic system (CAS) are the essential components. The state of CAS can be evaluated with I-123metaiodobenzylguanidine (MIBG), which is a norepinephrine analog and a tracer for sympathetic neuron integrity and function. Therefore, imaging of CAS with MIBG may further refine HF patient selection, beyond LVEF, for ICD implantation.4-6 Most published studies on the use of MIBG imaging in HF patients is based on measurements from planar images, with cardiac uptake quantified by the heart-tomediastinum ratio (H/M).7 It was demonstrated that decreased values of late H/M from planar imaging can predict potentially fatal arrhythmic events (including resuscitated cardiac arrest, sustained ventricular tachyarrhythmia, or appropriate ICD therapy) as well as cardiac death (including SCD) in patients with HF and thereby help guide the use of ICD.8 The ADMIRE-HF trial demonstrated in a large prospective study that the late H/M from planar images was an independent predictor of potentially life-threatening arrhythmic event (AE).9 In most of those planar studies, cardiac uptake of MIBG was dichotomized to differentiate high-risk from low-risk populations. To assess the full scope of the Teresińska Iodine-123-metaiodobenzylguanidine cardiac SPECT imaging Journal of Nuclear CardiologyÒ prognostic potential of MIBG, in the meta-analysis performed by Verschure et al., the late H/M from planar images was used as a continuous parameter and in multivariate analysis was not an independent predictor for arrhythmias.10 SPECT technique had been applied to CAS assessment shortly after MIBG introduction for human heart imaging, as the parameters obtained with planar technique provide only global information while 3D imaging has a potential to evaluate global as well as regional innervation. It has been proposed that patients with MIBG regional defects, especially in areas of preserved perfusion, what has been shown to predispose to denervation super-sensitivity, are especially susceptible to potentially fatal VAs.11 For this reason, the results of MIBG SPECT and perfusion SPECT have been often compared by identifying segments with adrenergic/perfusion mismatches.6 A few small-cohort studies using semi-quantitative visual scoring techniques suggested clinical utility for SPECT MIBG in assessing arrhythmic risk.12-15 Arora et al. studied retrospectively 17 patients with ICD implanted 14 ± 11 months earlier. Patients with ICD discharges had higher MIBG defect scores and a higher number of mismatching segments.12 Bax et al., in a prospective study of 50 patients with prior MI, showed that the only variable differentiating between positive and negative inducible ventricular tachycardia (VT) in an electrophysiologic study was the late MIBG SPECT results, with a late summed score (LSS) C 37 having a sensitivity of 77% and a specificity of 75% for predicting electrophysiologic results.13 Boogers et al. studied prospectively 116 patients before ICD implantation. Over a mean of 23 months, the LSS was an independent predictor of appropriate ICD therapy and patients with LSS [ 26 showed significantly more appropriate ICD therapy than patients with a smaller defect.14 Marshall et al., in a prospective study of 27 patients referred for ICD in primary prevention, during median follow-up of 16 months showed that patients who experienced a significant AE had higher early SPECT summed scores (ESS) and higher mismatch scores. Optimal threshold for predicting arrhythmias was C 31 for ESS, with a sensitivity of 78% and a specificity of 77%.15 All those studies demonstrated (by using binary categorizations of event risk) that the larger the extent of SPECT MIBG abnormality, the greater the likelihood of VT and two of them showed the same also for the innervation/perfusion mismatch score. However, a large international multicenter prospective ADMIRE-HF trial did not show clinical utility for MIBG SPECT in assessing arrhythmic risk during original analysis of the results in 961 patients.9 Secondary rigorous analysis of MIBG SPECT and perfusion images from ADMIREHF, performed in 471 patients with ischemic HF, also failed to identify the subjects at higher risk of experiencing an AE during 24-month follow-up. On multiv (...truncated)