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 I-123-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 I-123-mIBG myocardial imaging, as well as echocardiography and gated SPECT Tc-99m-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 I-123-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 I-123-mIBG images, as well as from Tc-99m-tetrofosmin SPECT and echocardiography. Conclusion. The results of the ADMIRE-HF trials will provide prospective validation of the potential role of I-123-mIBG scintigraphy in assessing prognosis and developing management strategies for patients with heart failure. (J Nucl Cardiol 2009; 16: 113-21)