Heart disease is a major global threat. Triglyceride deposit cardiomyovasculopathy (TGCV) is an emerging, noncommunicable, adult-onset heart disease, first identified in Japanese patients with heart failure (HF) requiring cardiac transplantation1-3. In TGCV, defective intracellular lipolysis of long-chain triglycerides (TGs) results in cellular steatosis and energy failure mainly in cardiomyocytes4 and smooth muscle cells5, leading to HF, diffuse coronary artery disease with TG deposition and ventricular arrhythmias with high mortality6. Tricaprin, a class of medium-chain TGs, recently corrected myocardial TG lipolysis7. Here we report remarkable long-term survival and durable recovery of HF in patients with TGCV treated with supplemental tricaprin in registry studies. Our study offers a classification of heart disease caused by defective lipolysis and its possible practical treatment. Because myocardial lipid droplets are a common feature in HF and their potential as therapeutic targets has been discussed worldwide, our findings warrant investigation into other ethnicities.

Triglyceride deposit cardiomyovasculopathy (TGCV) (Orphanet ORPHA code: 692305) is an emerging rare adult-onset cardiovascular disease, first identified in Japan. In TGCV, defective intracellular lipolysis of long-chain triglycerides results in cellular steatosis and energy failure, leading to intractable heart failure, diffuse coronary artery disease, and ventricular arrhythmia. A hallmark of TGCV diagnosis is the reduced washout rate (WR) of 123I-β-methyl-p-iodophenyl pentadecanoic acid (BMIPP), a well-established radiopharmaceutical of long-chain fatty acid (LCFA). Recently, the working group of the Japanese Society of Nuclear Cardiology published the practical guideline for measuring 123I-BMIPP-WR. Here, we present the diagnostic principle of TGCV using 123I-BMIPP-WR based upon basic and clinical studies in nuclear cardiology as well as current biochemical insights into TG and LCFA metabolism.

Background: In nuclear cardiology, tracer uptake and washout rate (WR) are key parameters for evaluating cardiac pathophysiology. However, WR is influenced by counts in the early image, making it difficult to evaluate pathophysiology based on WR value alone. To differentiate cardiovascular diseases involving count and WR variations, such as triglyceride deposit cardiomyovasculopathy (TGCV) and old myocardial infarction (OMI), we proposed a method to simultaneously evaluate both. Methods: We newly developed the Count-Washout Rate Polar Map (CWRM), a graphical representation of the count and WR values in a polar coordinate system. CWRM consists of two axes: count in the early image and WR. Given the variety of diseases characterized by count and WR, Iodine-123-β-methyl-p-iodophenyl-pentadecanoic acid was selected as the radiotracer. We examined patients without cardiovascular disease (normal) and patients with TGCV, OMI, and TGCV with OMI. CWRMs for each disease were visually evaluated. Results: In the normal case, sufficient counts were observed in the early image, and WR did not decrease; CWRM showed light blue. In TGCV, sufficient counts were observed in the early image, but WR markedly decreased; CWRM showed orange evenly. In non-TGCV with OMI, regions with decreased and preserved counts coexisted; CWRM showed light blue in the normal region and black in the OMI region. In TGCV with OMI, CWRM showed orange in the TGCV myocardium and black in the OMI region. Conclusion: CWRM is useful for at-a-glance differentiation of patients with TGCV, OMI, and TGCV with OMI, thereby showing potential as a new diagnostic indicator.

Triglyceride-deposit cardiomyovasculopathy (TGCV) is characterized by diffuse narrowing of the coronary arteries because of triglyceride-deposit atherosclerosis. However, the plaque characteristics and prognosis of TGCV in patients with diffuse coronary artery disease remain unclear. This study aimed to describe the morphology of coronary arteries in TGCV using integrated backscatter intravascular ultrasound (IB-IVUS) and assess the effects on clinical outcomes. This single-center, retrospective observational study compared the IB-IVUS findings and clinical outcomes of patients with native coronary lesions of TGCV with those of patients with non-TGCV, all of whom had diffuse coronary artery disease. TGCV was diagnosed as (1) a low washout rate of iodine-123-β-methyl iodophenyl-pentadecanoic acid (BMIPP; <10%) on BMIPP single-photon emission computed tomography and (2) diffuse narrowing of the coronary arteries on coronary angiography. Thirty-one patients with diffuse coronary artery disease who underwent percutaneous coronary intervention were enrolled. Among these patients 10 (32%) were diagnosed with TGCV. IB-IVUS revealed that TGCV lesions had a significantly smaller ratio of the lipid area than non-TGCV lesions (20% ± 0.8% vs 23% ± 0.5%, p = 0.02). Conversely, the ratio of the calcification area tended to be larger. The Kaplan-Meier analysis revealed a significant increase in the rates of major adverse cardiovascular events in the TGCV group (p = 0.01). Patients with diffuse coronary artery disease present TGCV characterized by a smaller ratio of the lipid area. TGCV might be associated with worse clinical outcomes. The study findings may contribute to its early diagnosis and management.

Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare cardiovascular disorder caused by defective intracellular lipolysis of triglyceride, resulting in heart failure and diffuse narrowing atherosclerosis. Recently, the registry of TGCV patients in Japan revealed that the 3-year overall survival rate was 80.1% and the 5-year overall survival rate was 71.8%. In this study, the effect on mortality of chronic kidney disease (CKD), diabetes malleus (DM), hypertension (HT), and dyslipidemia (DL) was analyzed using this retrospective registry of TGCV patients. The 3-year survival rate was 71.3% in the CKD group and 91.7% in the non-CKD group, and the 5-year survival rate was 61.8% in CKD group and 84.4% in the non-CKD group. The Kaplan-Meier analysis revealed that CKD is a risk factor for mortality in TGCV patients (p = 0.006). Although TGCV patients with CKD were older than those without CKD, Cox proportional hazard model analyses including age indicated that CKD has a significant association of the prognosis of TGCV patients (hazard ratio 2.33 [1.12-4.86], p = 0.024). DM, HT, and DL did not increase mortality in TGCV patients, although these risk factors were established in the general population. TGCV might cause cardiac disorders and kidney disease at the same time, because podocyte foot process disorder in the glomeruli might be caused by TGCV itself, while CKD should be a risk factor for mortality in TGCV patients as is true in the general population. In conclusion, CKD is a major risk factor for mortality in TGCV patients and thus should be paid attention to in these patients.