MYOCARDIAL LIPID TURNOVER IN DILATED CARDIOMYOPATHY - A DUAL IN-VIVO TRACER APPROACH

Background. Myocardial lipid metabolism appears abnormal in dilated ca rdiomyopathy (DCM). A dual-tracer approach with two different fatty ac id analogs may allow us to observe such alteration in vivo. 15-(Ortho- I-123-phenyl)-pentadecanoic acid (oPPA) and 15-(para-I-123-phenyl) -pe ntadecanoic acid (pPPA) have similar kinetics in circulation, diffusio n, and transport. However, pPPA in normal myocardium undergoes beta-ox idation and may also be lost from myocardial cells through back-diffus ion; oPPA is hardly catabolized and normally retained mainly in the cy tosolic lipid pool. Use of both pPPA and oPPA in the dual-tracer appro ach focuses observation on the turnover of myocardial lipids (with pPP A) that is scaled against loss of fatty acid through back-diffusion in to circulation (with oPPA). Methods and Results. Fifteen patients with idiopathic DCM and five control subjects were given oPPA and pPPA seq uentially for dynamic planar scintigraphy. Uptake and elimination rate s were determined for both substrates from three myocardial regions pe r individual; the corresponding six elimination rate constants and the three differences between them were analyzed for significant alterati ons in patients from control values. At least 66% of the patients had a significant alteration in myocardial lipid turnover in three types o f patterns: (1) increased beta-oxidation, (2) decreased beta-oxidation , and (3) increased back-diffusion, in part associated with decreased beta-oxidation. Even with the limited number of patients and control s ubjects, the pattern of abnormality of lipid turnover in DMC appeared to be consistent individually but heterogeneous in the patient group. Moreover, a highly significant increase in beta-oxidation was observed for the posterolateral region of the myocardium compared with the ant eroseptal and apical regions in control subjects and patients. Conclus ion. The dual-tracer approach uncovered in vivo that in at least two t hirds of the patients with DCM myocardial lipid turnover was significa ntly altered compared with control values.