Improvement of myocardial lipolysis in iodine-123-beta-methyl-P-iodophenyl-pentadecanoic acid scintigraphy in patients with idiopathic triglyceride deposit cardiomyovasculopathy treated with Tricaprin

Abstract Background Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare intractable cardiovascular disorder (Orphanet ORPHAcode: 565612) in which defective intracellular lipolysis results in heart failure and coronary artery disease. Myocardial scintigraphy with iodine-123-β-methyl-P-iodophenyl-pentadecanoic acid (BMIPP) is useful for evaluating myocardial TG metabolism and its washout rate (WR) reflects myocardial lipolysis. A decreased WR (<10%) of BMIPP is one of the diagnostic criteria for TGCV. CNT-01, the active ingredient of which is tricaprin, a medium-chain triglyceride, has the potential to facilitate myocardial lipolysis in a mouse model. However, the effects of CNT-01 (tricaprin) on BMIPP scintigraphy in patients with TGCV remain unclear. Purpose To evaluate the effects of CNT-01 on BMIPP-WR in patients with TGCV. Methods An investigator-initiated, randomized, double-blind exploratory trial (Phase IIa) was conducted. Ten patients with idiopathic TGCV in our hospital were enrolled and orally administered 1.5 g/day of CNT-01 or placebo for 8 weeks. The endpoint was the delta WR on BMIPP scintigraphy. All the participants underwent BMIPP scintigraphy after overnight fasting. Following the protocol recommended by the Japanese Society of Nuclear Cardiology, 111 MBq of BMIPP was intravenously injected at rest after fasting for ≥ 12 h. Early and delayed images were obtained after 20 and 180–210 min, respectively. BMIPP scintigraphy at baseline and 8-week was performed using the same SPECT apparatus. WR is defined as the ratio of the difference between the counts in the early image and time-decay-corrected delayed image divided by the former. We used a recently proposed algorithm for calculating the WR based on the total count and analyzed the WRs (Ann Nucl Cardiol. 2023;9(1):19-25). Results A total of 5 patients were assigned to placebo and 5 patients were assigned to CNT-01. During the protocol, delta BMIPP-WRs were -6.18 ± 4.43 and 5.44 ± 2.57 % (95% confidence intervals, -12.33 to -0.03 and 1.88 to 9.00) in the placebo and CNT-01 groups, respectively. The baseline-adjusted difference in delta BMIPP-WR between the two groups was significant (p=0.005) (Picture). No significant changes were observed in clinical parameters. Conclusion This study demonstrated that CNT-01 improved myocardial lipolysis in patients with TGCV as measured by BMIPP scintigraphy.