Impaired cardiac adrenergic innervation assessed by MIBG imaging as a predictor of treatment response in childhood dilated cardiomyopathy.

Abstract

Objective--To evaluate the prognostic value of metaiodobenzylguanidine (MIBG) imaging in childhood cardiomyopathy.

Design--Prospective cohort study.

Setting--Tertiary referral centre.

Patients--40 children (21 boys, 19 girls; mean (SD) age, 7.0 (5.6) years) with heart failure resulting from idiopathic dilated cardiomyopathy (n = 23) or various other disorders (n = 17).

Methods--At the initial examination, cardiac [I.sup.123]-MIBG uptake and release, circulating noradrenaline (norepinephrine) concentration, x ray cardiothoracic ratio, and echocardiographic variables were recorded. Cardiac MIBG uptake was obtained by measuring the heart to mediastinum activity ratio on the planar image obtained four hours after MIBG injection. MIBG washout rate was evaluated using relative decrease in cardiac activity measured at 20 minutes and four hours. Patients were treated with angiotensin converting enzyme inhibitors, diuretics, and digitalis, and were followed up for 12 (10) months. Fifteen patients did not respond to medical treatment (12 heart transplants; three deaths), and 25 did respond (improved or stable).

Results--Cardiac MIBG uptake was positively correlated with x ray cardiothoracic index (r = 0.55, p = 0.0008) and echocardiographic left ventricular fractional shortening (r = 0.68, p [less than] 0.0001). Among all the clinical and laboratory variables tested, multivariate discriminant analysis showed that the only independent predictor of an unfavourable outcome was a low MIBG uptake (p [less than] 0.001). Survival curves had a mean threshold value of 1.54 for MIBG uptake.

Conclusions--Impaired cardiac adrenergic innervation is strongly related to adverse outcome in children with dilated cardiomyopathy, independently of the aetiology. MIBG imaging may help to stratify risk in such patients.

(Heart 2001;85:692-696)

Keywords: noradrenaline; MIBG; single photon imaging; children; cardiomyopathy

Complex and severe neurohormonal system disorders have been reported in adult dilated cardiomyopathies. [1-4] There are few data on the sympathetic nervous system response to heart failure in children. [5] [123]I-metaiodobenzyl guanidine (MIBG) imaging provides a means of non-invasively evaluating cardiac adrenergic nerve activity in vivo, as MIBG is subject to the same uptake and storage mechanisms as noradrenaline (norepinephrine). MIBG is internalised by neuronal cells through the uptake-1 system, a transporter and energy dependent system, whereas it enters myocytes through the uptake-2 system, the activity of which is very low in the human heart. [6] Cardiac MIBG uptake is dramatically decreased in the failing adult human heart, and there are data indicating that this decrease is related to mortality. [7-9]

The limited availability of cardiac transplantation, with a long waiting list, has increased the importance of accurate and early prognostic evaluation to identify eligible patients. Paediatric cardiologists need better and more objective prognostic indicators than clinical status to determine the indications for heart transplantation. The value of MIBG imaging in childhood cardiomyopathy is at present unknown, and its potential as a prognostic tool has not yet been explored. In this study we examined disorders of the neurohormonal system using MIBG imaging, and evaluated the prognostic value of MIBG in childhood cardiomyopathy.

Methods

STUDY POPULATION

Forty children, 21 boys and 19 girls (mean (SD) age, 7.0 (5.6) years) entered the study. All had dilated cardiomyopaqthy with a hypokinetic left ventricle on cross sectional echocardiography (fractional shortening [less than] 30%). None had a hypertrophic left ventricle. Cardiomyopathy was idiopathic in 23 patients and had an identifiable cause in the remaining 17 (anthracyclin toxicity in seven, mitochondrial respiratory chain defect in seven, postarrhythmia in two, and postischaemia in one). Before entering the study,…