Original Article
Assessment of 123I-mIBG and 99mTc-tetrofosmin single-photon emission computed tomographic images for the prediction of arrhythmic events in patients with ischemic heart failure: Intermediate severity innervation defects are associated with higher arrhythmic risk

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Abstract

Rationale

123I-mIBG planar image heart-to-mediastinum ratios effectively risk-stratify heart failure (HF) patients. The value of single-photon emission computed tomographic (SPECT) imaging for identifying increased risk of ventricular arrhythmias is less clear. This study sought to determine if findings from simultaneous interpretation of 123I-mIBG and 99mTc-tetrofosmin SPECT are predictive of arrhythmic events (ArEs).

Methods

123I-mIBG SPECT images from 622 patients with ischemic HF were presented in standard displays alongside 99mTc-tetrofosmin images. Consensus interpretations using a 17-segment model produced summed scores. Cox proportional hazards analyses related findings to adjudicated ArEs over 2 years.

Results

471 patients had images adequate for total 17-segment scoring. There were 48 ArEs (10.2%). Neither 123I-mIBG nor 99mTc-tetrofosmin SPECT summed scores were univariate predictors. On multivariate proportional hazards analysis, the 123I-mIBG SPECT score was independently predictive of ArEs (HR: 0.975, 95% CI 0.951-0.999, P = 0.042), but HR<1 indicated that risk decreased with increasing score. This occurred because patients with intermediately abnormal SPECT studies had a higher likelihood of ArEs compared to patients with extensive abnormalities.

Conclusions

The presumption of a monotonic increase in ArE risk with increasing summed 123I-mIBG SPECT score may not be correct as ischemic HF patients with abnormalities of intermediate extent appear at highest risk.

Introduction

The ability of I-123 meta-iodobenzylguanidine (123I-mIBG) cardiac imaging to risk-stratify heart failure (HF) patients with reduced ejection fraction (EF) has been demonstrated.1, 2, 3, 4, 5, 6 In particular, 123I-mIBG imaging has the potential for identifying patients at low versus increased risk for lethal or potentially lethal ventricular arrhythmic events (ArEs).5,7, 8, 9

Most published 123I-mIBG studies have risk-stratified patients based on global cardiac uptake using planar images via the heart-to-mediastinum ratio (HMR). However, planar imaging is limited because, unlike single-photon emission computed tomographic (SPECT) imaging, it does not well identify regional myocardial innervation abnormalities that early investigations suggested increase susceptibility to arrhythmias.10,11 There is also evidence that regions of innervation/perfusion mismatch, i.e., 123I-mIBG defect(s) with preserved perfusion, also predispose to arrhythmias.12,13 Thus, SPECT imaging should improve upon planar data alone. Several studies have investigated the utility of 123I-mIBG SPECT to identify arrhythmic risk but are limited by relatively small patient cohorts.14, 15, 16, 17, 18

The international, multicenter prospective ADMIRE-HF trial of subjects with New York Heart Association (NYHA) II-III HF and left ventricular ejection fraction (LVEF) ≤35% showed that a lower 123I-mIBG image HMR was associated with a higher 2-year incidence of cardiac events.5 Although SPECT image interpretation was part of the ADMIRE-HF data analysis, findings did not show value for primary study endpoints that were dominated by HF progression events. Potential reasons for this lack of success included reading in a standard trial but uncustomary clinical manner of blinding readers to relevant demographic data; viewing innervation and perfusion images separately; and difficulty interpreting images with severely reduced cardiac uptake.

The primary objective of this investigation was to determine if rigorous expert consensus scoring of the ADMIRE-HF 123I-mIBG SPECT images processed with state-of-the-art reconstruction and interpreted using customary clinical methods improved identification of HF subjects at higher risk of experiencing an arrhythmic event during 24 months of follow-up. Performance of 123I-mIBG and 99mTc-tetrofosmin SPECT defect scores for prediction of cardiac and all-cause mortality was examined as secondary objectives. As a strong association between regional innervation abnormalities and susceptibility to arrhythmias has been demonstrated particularly in the ischemic setting,11, 12, 13,19,20 we chose to focus solely on patients with ischemic HF.

Section snippets

Patients

The study involved reanalysis of previously collected de-identified patient data and images from the international multicenter ADMIRE-HF study, which was approved by institutional review boards and ethics committees at each center, with all subjects signing written informed consents; specific study details have been reported previously.5,21 For ADMIRE-HF, the principal inclusion criteria were NYHA II or III HF (of ischemic or non-ischemic etiology) and LVEF ≤35%. Exclusion criteria relevant to

Results

Of 635 eligible patients, 13 had no 123I-mIBG images available for re-processing, and 1 had no HMR and was therefore not presented to readers. Of the remaining 621 patients, 75 (12.1%) had images judged non-diagnostic during consensus reads because of insufficient global cardiac uptake (n = 28), insufficient cardiac uptake that was further interfered with by high lung/liver uptake (n = 41), and unspecified technical issues (n = 6). Of these 75 patients, 44 (57.9%) had HMR <1.30, 29 (38.2%) had

Discussion

The present study was designed to examine the performance of 123I-mIBG SPECT results as a predictor of occurrence of ArEs in ischemic HF subjects. The decision to examine this subpopulation of ADMIRE-HF subjects was based on the high likelihood of identifying discrete regional innervation and perfusion defects that would be more readily associable with occurrence of ArEs. The judgment was that if a significant relationship between 123I-mIBG imaging findings and ArE probability could not be

New Knowledge Gained

123I-mIBG SPECT imaging is useful for arrhythmic risk stratification in patients with HF. However, arrhythmic risk stratification with adrenergic imaging may be more complicated because of the possibility that event rates may not increase monotonically with the extent of abnormality.

Conclusions

Adjusted for other variables such as LVEF and BNP, an intermediate extent of dysinnervation on 123I-mIBG SPECT imaging in patients with ischemic heart failure identified a small group of subjects at the highest arrhythmic event risk. Future large prospective 123I-mIBG studies should not be based on the a priori assumption that arrhythmic event risk increases monotonically with severity of abnormal sympathetic innervation. By avoiding use of incorrect models, it should be possible to gain a

Disclosure

Dr Jacobson was an employee of GE Healthcare at the time of the study, and the presented analyses were performed. Drs Travin, Henzlova, and Jain have received research support from GE Healthcare.

References (33)

Cited by (0)

See related editorial, doi:10.1007/s12350-016-0411-9.

This study was sponsored by GE Healthcare.

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