Triglyceride deposit cardiomyovasculopathy: a rare cardiovascular disorder

Abstract

Triglyceride deposit cardiomyovasculopathy (TGCV) is a phenotype primarily reported in patients carrying genetic mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) which releases long chain fatty acid (LCFA) as a major energy source by the intracellular TG hydrolysis. These patients suffered from intractable heart failure requiring cardiac transplantation. Moreover, we identified TGCV patients without PNPLA2 mutations based on pathological and clinical studies . We provided the diagnostic criteria, in which TGCV with and without PNPLA2 mutations were designated as primary TGCV (P-TGCV) and idiopathic TGCV (I-TGCV), respectively. We hereby report clinical profiles of TGCV patients. Between 2014 and 2018, 7 P-TGCV and 18 I-TGCV Japanese patients have been registered in the International Registry. Patients with I-TGCV, of which etiologies and causes are not known yet, suffered from adult-onset severe heart disease, including heart failure and coronary artery disease, associated with a marked reduction in ATGL activity and myocardial washout rate of LCFA tracer, as similar to those with P-TGCV. The present first registry-based study showed that TGCV is an intractable, at least at the moment, and heterogeneous cardiovascular disorder.

The evolving systemic biomarker milieu in obese ZSF1 rat model of human cardiometabolic syndrome: Characterization of the model and cardioprotective effect of GDF15

“…CPT1 inhibition has demonstrated beneficial effect in HF [52], and UCP3 was considered a marker for cellular metabolic state [53]. Mutations in PNPLA2 (which encodes adipose triglyceride lipase, ATGL) have been associated with triglyceride deposit cardiomyovasculopathy (TCGV) [54]. Mori et al .…”

Ceramide Content in Liver Increases Along with Insulin Resistance in Obese Patients

“…This state is associated with lipids accumulation not only in adipose tissue, but also in other tissues, such as skeletal muscle and the liver. Lipids storage in non-adipose tissue is thought to lead to several metabolic disturbances, including insulin resistance, type 2 diabetes (T2D) and cardiovascular disease [1][2][3][4]. Obesity has reached epidemic proportions worldwide, therefore insulin resistance and type 2 diabetes have become one of the most common chronic metabolic disorders.…”

A historical case of primary triglyceride deposit cardiomyovasculopathy

“…We provided the diagnostic guideline and criteria for TGCV, in which TGCV is classified into primary and idiopathic types with and without PNPLA2 mutation, respectively. 5 Furthermore, we launched the international registry for TGCV and NLSDs (ClinicalTrials.gov Identifier: NCT02918032). 5 The registered data indicate that primary TGCV (P-TGCV) is a clinical continuum with NLSD-M, because the former and latter dominantly express cardiac and skeletal muscle involvements, respectively, whereas both carry genetic PNPLA2 mutation.…”

“…5 Furthermore, we launched the international registry for TGCV and NLSDs (ClinicalTrials.gov Identifier: NCT02918032). 5 The registered data indicate that primary TGCV (P-TGCV) is a clinical continuum with NLSD-M, because the former and latter dominantly express cardiac and skeletal muscle involvements, respectively, whereas both carry genetic PNPLA2 mutation. The Japan TGCV study group reached a consensus that the present patient is a historical case with P-TGCV based on the followings: (i) a typical JA; (ii) Thin layer chromatography showed a definite increase of TG of homogenized myocardium (data not shown); (iii) Clinicopathological phenotypes including IMS of the present case with severe heart disease were consistent with those with P-TGCV cases so far reported, 5 impossible; (iv) This patient had neutral lipid storage in skeletal muscle as mentioned above, which is the phenotype of NLSD-M. P-TGCV and NLSD-M is an ultra-rare and life-threatening and disabling disorder.…”