| Domain | Key findings for Primary TGCV | Key quantitative details | Key source (year; URL) | Citation |
|---|---|---|---|---|
| Disease / definition | Primary triglyceride deposit cardiomyovasculopathy (TGCV) is the PNPLA2/ATGL-mutation form of TGCV, a rare cardiovascular lipid-storage disorder caused by defective intracellular triglyceride lipolysis with triglyceride accumulation in myocardium and coronary arteries; TGCV was encoded in Orphanet as ORPHA:565612. Synonyms/related names in sources: TGCV, triglyceride-deposit cardiomyovasculopathy, “obesity of the heart”; classified as primary TGCV (with PNPLA2 mutation) vs idiopathic TGCV (without PNPLA2 mutation). | ORPHA:565612; >200 clinically diagnosed cases in Japan by 2020. | Kobayashi et al., 2020; https://doi.org/10.17996/anc.20-00131 | (pqac-00000016, pqac-00000017) |
| Causative gene / inheritance | Causative gene for primary TGCV: PNPLA2, encoding adipose triglyceride lipase (ATGL), the rate-limiting enzyme for intracellular TG hydrolysis. Primary TGCV is associated with homozygous PNPLA2 deficiency and overlaps clinically with neutral lipid storage disease with myopathy (NLSDM; OMIM 610717), which is autosomal recessive. | 10 different homozygous PNPLA2 mutations reported in primary TGCV; only 15 primary TGCV cases identified in Japan by 2024. | Hirano et al., 2024; https://doi.org/10.7793/jcad.30.005 ; Wang et al., 2024; https://doi.org/10.3389/fgene.2024.1415156 | (pqac-00000036, pqac-00000032, pqac-00000034) |
| Example pathogenic variant evidence | Recent PNPLA2-related cardiac disease evidence includes homozygous splice-site variant NM_020376.4:c.757+1G>T causing severe dilated cardiomyopathy with mild skeletal myopathy in NLSDM/ATGL deficiency, supporting the PNPLA2-primary TGCV disease spectrum. | Cardiac involvement reported in ~40–50% of NLSDM; review summarized 49 previously reported cardiomyopathy cases. | Wang et al., 2024; https://doi.org/10.3389/fgene.2024.1415156 | (pqac-00000030, pqac-00000032, pqac-00000034) |
| Core clinical features | Primary TGCV presents with adult-onset severe heart disease: heart failure, coronary artery disease with diffuse/concentric multivessel narrowing, ventricular arrhythmia, chest pain/angina, dyspnea/palpitation; skeletal myopathy is typical in primary but absent in idiopathic TGCV. | Registry: symptom onset 37.7 ± 9.2 y (primary) vs 55.9 ± 12.5 y (idiopathic); heart failure 5/7 primary; critical arrhythmia 4/7 primary; diffuse narrowing 5/5 angiographed primary cases; skeletal myopathy 7/7 primary. | Li et al., 2019; https://doi.org/10.1186/s13023-019-1087-4 | (pqac-00000020, pqac-00000021) |
| Pathology / disease signature | Distinctive pathology is TG-deposit atherosclerosis rather than cholesterol-driven plaque: coronary arteries can “exclusively accumulate TG, but not cholesterol,” with TG-laden foam cells in endothelium, intima, media, and adventitia; cardiomyocyte steatosis is prominent. | Myocardial TG 3.64 mg/g vs control 1.4 ± 1.0 mg/g; coronary TG 19.44 mg/g vs control 6.2 ± 4.8 mg/g in a representative case. | Li et al., 2019; https://doi.org/10.1186/s13023-019-1087-4 ; Hirano et al., 2024; https://doi.org/10.7793/jcad.30.005 | (pqac-00000019, pqac-00000001) |
| Diagnostic criteria (essential items) | Essential items in Diagnostic Criteria 2020: impaired LCFA metabolism or myocardial TG deposition demonstrated by one of: decreased 123I-BMIPP washout rate, myocardial TG deposition on biopsy, or myocardial TG deposition by CT/MR spectroscopy. | BMIPP washout threshold: <10%. | Kobayashi et al., 2020; https://doi.org/10.17996/anc.20-00131 | (pqac-00000017, pqac-00000022) |
| Diagnostic criteria (major items) | Major items: reduced LVEF, diffuse coronary narrowing on angiography/CTA, or typical Jordans’ anomaly in peripheral polymorphonuclear leukocytes. Definite TGCV requires ≥1 essential + ≥1 major item; probable TGCV requires ≥1 essential item. | LVEF threshold <40%; Jordans’ anomaly defined as apparent vacuoles >1 μm in >90% of polymorphonuclear leukocytes. | Kobayashi et al., 2020; https://doi.org/10.17996/anc.20-00131 | (pqac-00000017, pqac-00000022) |
| Diagnostic biomarkers / phenotype contrast | Primary TGCV shows very low leukocyte ATGL activity and near-universal Jordans’ anomaly, with markedly reduced BMIPP washout. Idiopathic TGCV also has impaired BMIPP washout but much less frequent leukocyte vacuolization. | ATGL activity 5.3 ± 8.3 nmol/h/mg (primary) vs 12 ± 9 (idiopathic) vs reference 52 ± 13; vacuolated polymorphonuclear leukocytes ~100% in primary vs <10% in idiopathic; BMIPP washout −3.2 ± 4.8% in primary vs 1.4 ± 8% in idiopathic vs reference 19.4 ± 3.2%. | Li et al., 2019; https://doi.org/10.1186/s13023-019-1087-4 | (pqac-00000005, pqac-00000021) |
| Epidemiology / population | TGCV remains concentrated in Japanese reports/registries. Awareness has expanded from >200 diagnosed cases in 2020 to >800 cumulative cases across >100 hospitals in all 47 prefectures by 2024; primary TGCV is much rarer than idiopathic TGCV. | Estimated prevalence ~1 in 3,000; >800 cumulative diagnosed TGCV cases; 15 primary TGCV cases. | Hirano et al., 2024; https://doi.org/10.7793/jcad.30.005 ; Kobayashi et al., 2020; https://doi.org/10.17996/anc.20-00131 | (pqac-00000001, pqac-00000018, pqac-00000016) |
| Prognosis | TGCV has poor prognosis with substantial cardiovascular event burden; primary registry data also showed high mortality among early primary cases. | 5-year overall survival 71.8%; 5-year cardiovascular event-free survival 54.0%; historical registry deaths 5/7 primary and 3/18 idiopathic; 2025 registry report cites 3-year OS 80.1% and 5-year OS 71.8%, with CKD worsening survival. | Hirano et al., 2024; https://doi.org/10.7793/jcad.30.005 ; Li et al., 2019; https://doi.org/10.1186/s13023-019-1087-4 ; Nagasawa et al., 2025; https://doi.org/10.1007/s10157-024-02618-z | (pqac-00000001, pqac-00000021, pqac-00000003) |
| Disease mechanism / model evidence | ATGL loss blocks intracellular TG hydrolysis, causing LCFA utilization failure, energy deficiency, lipotoxicity, cardiomyocyte steatosis, and TG-laden vascular smooth muscle cells. Atgl-knockout mice recapitulate myocardial lipid accumulation and dysfunction. | In Atgl-KO mice, tricaprin improved myocardial CT value from −27.5 ± 5.7 HU to 8.1 ± 5.5 HU and LVEF from 15 ± 9% to 30 ± 12% (p<0.01). | Suzuki et al., 2018; https://doi.org/10.5650/jos.ess18037 | (pqac-00000039, pqac-00000038) |
| Treatment concept | Disease-specific therapy in development is CNT-01 (tricaprin/trisdecanoin), a medium-chain triglyceride intended to bypass defective LCFA/TG handling and improve myocardial lipolysis; supportive standard HF/CAD care and revascularization are often still required. | CNT-01 designated under Japan’s SAKIGAKE system in 2020; three investigator-initiated clinical trials completed by 2020. | Kobayashi et al., 2020; https://doi.org/10.17996/anc.20-00131 | (pqac-00000016, pqac-00000017) |
| Key clinical trial: randomized phase IIa | Multicenter randomized double-blind exploratory phase IIa trial in idiopathic TGCV tested oral CNT-01 vs placebo for 8 weeks; proof-of-mechanism endpoint was improvement in BMIPP washout. | 17 patients; CNT-01 1.5 g/day for 8 weeks; delta BMIPP-WR −0.26 ± 3.28% placebo vs 7.08 ± 3.28% CNT-01; baseline-adjusted p=0.035. | Miyauchi et al., 2022; https://doi.org/10.17996/anc.22-00167 | (pqac-00000014, pqac-00000029) |
| 2023 imaging implementation | A 2023 case report used 1H-MRS to quantify therapeutic response to CNT-01, showing reduced myocardial TG content after short-term therapy; this is one of the clearest 2023 translational implementations. | Oral CNT-01 1.5 g/day for 8 weeks; BMIPP-WR increased 5.1% → 13.3%; myocardial TG content by 1H-MRS decreased 8.4% → 5.9%; no adverse effects reported. | Aikawa et al., 2023; https://doi.org/10.1530/edm-22-0370 | (pqac-00000012, pqac-00000013, pqac-00000010) |
| 2024 real-world case implementation | In a 2024 ACS case, diagnosis used BMIPP scintigraphy plus biopsy, and CABG plus tricaprin was followed by radiographic regression of diffuse coronary lesions and metabolic improvement. | Baseline BMIPP-WR 3.1%; post-treatment BMIPP-WR 21.5%; follow-up at 1.5 years showed regression/dilatation of diffuse native coronary stenoses and ECV reduction 41% → 36%. | Yamamoto et al., 2024; https://doi.org/10.1016/j.cjco.2024.06.004 | (pqac-00000009, pqac-00000011) |
| Clinical trial / registry identifiers | Relevant study registrations include a completed CNT-01 safety study, a completed national registry, and an international NLSD/TGCV registry. | NCT02502578: completed phase I/II safety study, n=5; NCT05345223: completed registry, n=193, start 2022-03-31, completion 2023-12-31, primary endpoint all-cause death, secondary analyses before/after tricaprin; NCT02918032: recruiting international NLSD/TGCV registry, enrollment target 120. | ClinicalTrials.gov records: NCT02502578; NCT05345223; NCT02918032 | (pqac-00000025, pqac-00000027) |


*Table: This table condenses the most clinically actionable facts about primary triglyceride deposit cardiomyovasculopathy, including identifiers, PNPLA2/ATGL genetics, hallmark diagnostic criteria, registry epidemiology, prognosis, and tricaprin/CNT-01 treatment evidence. It is useful as a quick-reference artifact for disease knowledge base population and citation mapping.*