Correlation Perspectives for the Diagnosis of Idiopathic Triglyceride Deposit Cardiomyovasculopathy

Abstract

Background: Triglyceride (TG) deposit cardiomyovasculopathy (TGCV) is a novel cardiovascular disorder and was recently encoded as an orphan disease in Europe (ORPHA code: 565612). Defective lipolysis results in TG accumulation in the myocardium and coronary arteries in TGCV. The myocardial washout rate (WR) of iodine-123-β-methyl iodophenyl-pentadecanoic acid (BMIPP) is an essential indicator to evaluate myocardial lipolysis in vivo. TGCV is classified into primary and idiopathic type with and without PNPLA2 mutation, respectively. Here, we present the clinical correlation perspectives of TGCV patients in Chiba, Japan, to increase the awareness of this orphan disease and facilitate its diagnosis. Methods: We enrolled 234 patients who underwent BMIPP scintigraphy between September 2015 and July 2019. The diagnosis of TGCV was made based on the criteria we reported previously. Blood smear tests were performed for TGCV classification. The distributions of TGCV in each comorbidity were investigated. Results: In total, 104 patients were diagnosed with definitive idiopathic TGCV (I-TGCV). They had various comorbid conditions, including heart failure with reduced ejection fraction and multivessel coronary artery disease requiring revascularization. Moreover, the serum TG levels in I-TGCV patients were not high, and there was no correlation between serum TG level and BMIPP WR (n=205, p-value=0. 31), supporting the pathophysiological hypothesis of TGCV. Conclusion: I-TGCV patients showed multiple coexistence of coronary artery disease, heart failure of unknown etiology, or diabetes mellitus. For patients with such clinical characteristics, BMIPP scintigraphy and calculation of WR should be considered proactively for the diagnosis of TGCV.

¹²³I-BMIPP Scintigraphy Shows That CNT-01 (Tricaprin) Improves Myocardial Lipolysis in Patients with Idiopathic Triglyceride Deposit Cardiomyovasculopathy

“…Consistent with previous reports (3,6), patients in both groups showed normal serum lipid levels. Four patients in the placebo and two in the CNT-01 group had a medical history of ischemic heart disease.…”

“…The WR was calculated as the ratio of left ventricular (LV) myocardial counts with time decay correction to early uptake In order to minimize the intra-and inter-observer variabilities, WR was computed using the myocardial SPECT analysis software Heart Risk View-S (Nihon Medi-Physics, Co. Ltd., Tokyo, Japan), which was approved by the Ministry of Health, Labour, and Welfare (MHLW) of Japan, based on the data of SPECT short-axis images (6,10). The slices of analysis were carefully selected to determine exactly the same locations between pre-and post-intervention conditions.…”

“…As a result, patients with TGCV exhibit adult-onset HF and diffuse narrowing coronary artery disease (CAD). TGCV is classified into primary and idiopathic types with and without mutations of PNPLA2 encoding ATGL, respectively (3,6).…”

Methods of calculating 123I-β-methyl-P-iodophenyl-pentadecanoic acid washout rates in triglyceride deposit cardiomyovasculopathy

“…In accordance with recent diagnostic criteria, a washout rate (WR) of < 10% in myocardial 123 I-BMIPP single-photon emission computed tomography (SPECT) is essential for a diagnosis of TGCV [ 3 , 17 ]. However, the disadvantage is that BMIPP defects in early and delayed images are bothersome, and WRs increase in patients with ischemic coronary artery disease (CAD) [ 18 ]. Various ways of calculating WRs including planar and SPECT imaging have been applied in nuclear cardiology, but whether they can diagnose TGCV has not been evaluated.…”

Modified Algorithm Using Total Count for Calculating Myocardial Washout Rate in Single-Photon Emission Computerized Tomography

“…When using arithmetic mean WR, it might be confusing to differentiate TGCV which is sometimes accompanied with coronary artery disease (16), from other cardiovascular diseases with extensive myocardial necrosis. Therefore, physicians should devise a way, for example, to set an ROI in the non-defective regions.…”