ADMIRE-HF provides prospective validation of the independent prognostic value of (123)I-mIBG scintigraphy in assessment of patients with HF. (Meta-Iodobenzylguanidine Scintigraphy Imaging in Patients With Heart Failure and Control Subjects Without Cardiovascular Disease, NCT00126425; Meta-Iodobenzylguanidine [123I-mIBG] Scintigraphy Imaging in Patients With Heart Failure and Control Subjects Without Cardiovascular Disease, NCT00126438).

Pooled analyses of independent cohort studies confirmed the long-term prognostic value of cardiac mIBG uptake in patients with HF independently of other markers, such as NYHA functional class, BNP, and LVEF, and demonstrated that categoric assessments could be used to define meaningful thresholds for lethal event risk.

Application of a clinical trial methodology via the retrospective reanalysis of (123)I-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.

Background-Disturbances of autonomic function after infarction are associated with both total mortality and sudden death. Although many imaging techniques for assessing the cardiac autonomic nervous system have been studied, the clinical usefulness of these techniques remains uncertain. This exploratory pilot study examined the relationship between abnormalities of ventricular sympathetic innervation delineated by scintigraphic imaging with Clinical Perspective see p 140123 I-mIBG is a norepinephrine analogue, and myocardial uptake reflects the extent of sympathetic innervation. Reduced myocardial uptake of 123 I-mIBG is observed in asso- ciation with most diseases that result in left ventricular (LV) dysfunction and potentially lethal ventricular arrhythmias. [5][6][7][8][9][10][11][12][13][14][15] In small observational studies, dysfunction of the myocardial autonomic nervous system as evaluated by using 123 I-mIBG has been shown to be associated with the occurrence of arrhythmias. 16 -18 However, the explanation for this association is not yet clear. One potential link between abnormalities of sympathetic innervation and the occurrence of potentially lethal ventricular arrhythmias is the fact that denervated myocardium may be viable and hyperresponsive to circulating catecholamines. 3 It is also possible that denervated but viable myocardium on the border zone of infarctions is prone to the development of reentrant ventricular tachycardia circuits. Both single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging have been used to demonstrate the presence of denervated but still viable myocardium (as can be observed after myocardial infarction) that could contribute to the development of ventricular arrhythmias. 18 -26 The present exploratory pilot study was designed to examine whether alterations in cardiac sympathetic innervation as measured by 123 I-mIBG scintigraphy were related to the inducibility of ventricular arrhythmias during EP testing in patients with previous infarction. The primary objective was to evaluate results by using planar 123 I-mIBG imaging and the combination of SPECT 123 I-mIBG innervation and 99m Tctetrofosmin perfusion imaging (providing information on extent of denervated myocardium and infarct size, respectively). Methods Patient SelectionThis was a phase 2, open-label, multicenter exploratory study conducted at 13 centers in Europe and one center in the United States, investigating the association between findings on planar and SPECT 123 I-mIBG imaging and the results of cardiac EP testing. The protocol was approved by the ethical committees or institutional review boards at each participating institution. All patients provided written informed consent before the performance of any study procedures.Primary inclusion criteria at the inception of the study included a history of myocardial infarction, LV dysfunction (left ventricular ejection fraction [LVEF]Յ40%, measured within 30 days of study entry), and referral for a clinically indicat...