A Novel Clinical Entity: Triglyceride Deposit Cardiomyovasculopathy Implications and Perspectives from ''Obesity of the Heart''

Abstract

Heart diseases, including atherosclerotic cardiovascular disease and congestive heart failure, are major life-threatening disorders in most countries. Cholesterol is a vital causal factor and focus of research into heart diseases, but the involvement of triglycerides remains unclear. We recently reported a unique patient suffering from severe congestive heart failure and needing cardiac transplantation. Massive accumulation of triglycerides was observed in coronary atherosclerotic lesions as well as in the myocardium, while plasma triglyceride levels were normal. We suggested that this phenotype was a novel clinical entity and named it "Triglyceride deposit cardiomyovasculopathy", or simply "Obesity of the heart". The patient was identified as homozygous for a genetic mutation in the adipose triglyceride lipase, an essential molecule for hydrolysis of intracellular triglycerides. The present paper deals with what we can learn from this single case and discusses its implications for research and clinical medicine related to heart diseases.

Peripheral leukocyte anomaly detected with routine automated hematology analyzer sensitive to adipose triglyceride lipase deficiency manifesting neutral lipid storage disease with myopathy/triglyceride deposit cardiomyovasculopathy

“…In homozygous ATGL deficiency, once the clinical presentations of myopathy and cardiomyopathy occur, it has been difficult so far to regress or resolve symptoms through any conventional treatments [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]. We reported two patients with severe cardiomyovasculopathy and heart failure requiring cardiac transplantation [6], [8].…”

“…It presents profound lipid accumulation mainly in skeletal and cardiac muscles, manifesting neutral lipid storage disease with myopathy (NLSD-M)/triglyceride deposit cardiomyovasculopathy (TGCV) [3], [4], [5], [6], [7]. Only up to 40 patients have been reported globally [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]. Most of the reported cases were diagnosed in adulthood except for one case each in childhood and adolescence [12], [13].…”

“…Affected patients with ATGL deficiency exclusively exhibit persistent lipid droplets in the cytoplasm of circulatory neutrophils known as Jordans' anomaly (Fig. 1A) [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]. In earlier life, clinical symptoms seem to be absent or minimal in most cases, however Jordans' anomaly has been documented in subclinical or preclinical adolescents with ATGL deficiency [12], [13].…”

Role of Lipotoxicity in Endothelial Dysfunction

“…29 Accumulation of TG in the heart is associated with heart failure in animals and humans. 30,31 Thus, intracellular and plasma level of TG is associated with impairment of glucose tolerance and insulin resistance as well as CV dysfunction.…”

Quantitative proteomic analysis of cultured skin fibroblast cells derived from patients with triglyceride deposit cardiomyovasculopathy

“…This symptom has been designated “Triglyceride deposit cardiomyovasculopathy (TGCV)” [6,7]. Cardiomyopathy is lethal in patients with TGCV and necessitates cardiac transplantation; thus, therapeutic methods for reducing the burden on patients with this intractable disease are highly desirable.…”