A compartment model analysis for investigation of myocardial fatty acid metabolism in patients with hypertrophic cardiomyopathy

Abstract

Objective: The purpose of this study was to investigate the myocardial fatty acid metabolism in patients with hypertrophic cardiomyopathy (HCM) from dynamic SPECT through a compartment model analysis. Methods: Twenty-four normal controls, 7 patients with left ventricular hypertrophy (LVH) due to essential hypertension (eHT), and 30 patients with HCM were studied. I-123 BMIPP and Tc-99m tetrofosmin SPECT were performed. All the myocardium was divided into 13 segments, and totally 390 segments of HCM were categorized into early, moderately and severely advanced HCM segments, based on these SPECT imaging.By using the myocardial and blood pool time-activity curves, BMIPP pharmacokinetics was analyzed through a 2-compartment model. We defined k1 and k2 as influx and outflux rate constants between blood and myocardial reversible component, k3 as specific uptake rate constant between myocardial reversible and irreversible compartments. Results: The averages of k3 in HCM were higher than in normal. In contrast, the averages of k1/k2 in HCM were lower than in normal, and gradually decreased with progression of HCM. There are no significant differences in these indexes between normal controls and patients with LVH due to eHT.Conclusion: k3 might be a sensitive predictor for early detection of HCM, and k1/k2 could be a useful index to evaluate its progression. A mathematical compartment model analysis with BMIPP SPECT study might be useful not only for identification of HCM in very early stage, but also for evaluation of the progression of HCM.

Longitudinal Evaluation of Fatty Acid Metabolism in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic MicroSPECT Imaging

“…Our work also corresponds to work by Okizaki et al [5]. Using dynamic SPECT imaging of 123 I-BMIPP, they showed that fatty acid metabolism was higher in patients with hypertrophic cardiomyopathy.…”

“…In clinical settings, the abnormalities of fatty acid metabolism in hypertrophic cardiomyopathy can be recognized by the decreased uptake in single-photon emission computed tomography (SPECT) images [4]. It has also been demonstrated that compartmental analysis and dynamic SPECT imaging make it possible to detect abnormalities of fatty acid utilization earlier than SPECT imaging, with the potential to provide an even earlier prediction of the onset of cardiac hypertrophy [5]. There is a need to develop technology for imaging small animal models on clinical SPECT systems that could easily be translated to the clinic for diagnosis and management of patients with cardiac hypertrophy.…”

Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy

“…Previous studies (41,48) have shown that myocardial uptake of free fatty acids, as measured by 123 Ilabeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid, is reduced in patients with HCM (41,48). Here, we demon- Fig.…”

Imaging and Modeling of Myocardial Metabolism

“…Table 2 compares the advantages and disadvantages of PET, MRS, and SPECT for quantification of myocardial metabolism. Despite these limitations, Okizaki et al were able to perform a compartment model analysis of myocardial fatty acid metabolism in patients with hypertrophic cardiomyopathy using SPECT with 123I-beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP), a fatty acid analog and 99mTc-tetrofosmin perfusion radiotracer [29]. Using the myocardial and blood pool time-activity curves, 123I-BMIPP pharmacokinetics were analyzed through a two-compartment model.…”