Triglyceride Deposit Cardiomyovasculopathy Research Articles

Usefulness of visual classification for cardiac pathophysiology using count-washout rate map in iodine-123-beta-methyl-P-iodophenyl-pentadecanoic acid scintigraphy

Abstract Background Myocardial washout rate (WR) analysis of radiopharmaceuticals is utilized in nuclear cardiology to evaluate the clinical pathophysiology of the heart. WR is defined as the ratio of the difference between the counts in the early image and time-decay-corrected delayed image divided by the former. The myocardial WR of iodine-123-β-methyl iodophenyl-pentadecanoic acid (BMIPP) is an indicator of myocardial lipolysis, and a decreased WR (<10%) of BMIPP is one of the diagnostic criteria for triglyceride deposit cardiomyovasculopathy (TGCV). However, decreased BMIPP uptake in the early images, as in old myocardial infarction (OMI), would also cause a markedly decreased WR. Since the distinction between these clinical conditions cannot be made based on WR alone, simultaneous evaluation of the counts in the early image and WR is needed to properly understand the cardiac pathophysiology. Purpose To differentiate between TGCV and non-TGCV with OMI, both of which show decreased BMIPP WR, a new Count-WR Map (CWRM) method was evaluated. The purpose is to visually and easily distinguish between the two conditions using CWRM. Methods We introduced a CWRM consisting of two axes: counting in the early image, and WR. The count window was set to a maximum of the mean plus two standard deviations and a minimum of 50 counts, and the WR window was set to a maximum of 30 % and a minimum of -20%. CWRM was visually evaluated as normal, TGCV, non-TGCV with OMI, or TGCV with OMI. Results In normal cases, sufficient counts were observed in the early images, and WR did not decrease; CWRM showed light blue. In TGCV, sufficient counts were observed in the early image, but WRs markedly decreased; CWRM showed even orange. In non-TGCV with OMI, regions with decreased and preserved counts coexisted; CWRM showed light blue in the normal and black in the OMI region. In TGCV with OMI, CWRM showed orange in the TGCV myocardium and black in the OMI region (figure). Conclusions CWRM is useful for visually and easily differentiating TGCV from non-TGCV with OMI. CWRM can be applied to other cardiovascular diseases with count and WR variations for visual classification.

Improvement of myocardial lipolysis in iodine-123-beta-methyl-P-iodophenyl-pentadecanoic acid scintigraphy in patients with idiopathic triglyceride deposit cardiomyovasculopathy treated with Tricaprin

Abstract Background Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare intractable cardiovascular disorder (Orphanet ORPHAcode: 565612) in which defective intracellular lipolysis results in heart failure and coronary artery disease. Myocardial scintigraphy with iodine-123-β-methyl-P-iodophenyl-pentadecanoic acid (BMIPP) is useful for evaluating myocardial TG metabolism and its washout rate (WR) reflects myocardial lipolysis. A decreased WR (<10%) of BMIPP is one of the diagnostic criteria for TGCV. CNT-01, the active ingredient of which is tricaprin, a medium-chain triglyceride, has the potential to facilitate myocardial lipolysis in a mouse model. However, the effects of CNT-01 (tricaprin) on BMIPP scintigraphy in patients with TGCV remain unclear. Purpose To evaluate the effects of CNT-01 on BMIPP-WR in patients with TGCV. Methods An investigator-initiated, randomized, double-blind exploratory trial (Phase IIa) was conducted. Ten patients with idiopathic TGCV in our hospital were enrolled and orally administered 1.5 g/day of CNT-01 or placebo for 8 weeks. The endpoint was the delta WR on BMIPP scintigraphy. All the participants underwent BMIPP scintigraphy after overnight fasting. Following the protocol recommended by the Japanese Society of Nuclear Cardiology, 111 MBq of BMIPP was intravenously injected at rest after fasting for ≥ 12 h. Early and delayed images were obtained after 20 and 180–210 min, respectively. BMIPP scintigraphy at baseline and 8-week was performed using the same SPECT apparatus. WR is defined as the ratio of the difference between the counts in the early image and time-decay-corrected delayed image divided by the former. We used a recently proposed algorithm for calculating the WR based on the total count and analyzed the WRs (Ann Nucl Cardiol. 2023;9(1):19-25). Results A total of 5 patients were assigned to placebo and 5 patients were assigned to CNT-01. During the protocol, delta BMIPP-WRs were -6.18 ± 4.43 and 5.44 ± 2.57 % (95% confidence intervals, -12.33 to -0.03 and 1.88 to 9.00) in the placebo and CNT-01 groups, respectively. The baseline-adjusted difference in delta BMIPP-WR between the two groups was significant (p=0.005) (Picture). No significant changes were observed in clinical parameters. Conclusion This study demonstrated that CNT-01 improved myocardial lipolysis in patients with TGCV as measured by BMIPP scintigraphy.

Prevalence of triglyceride deposit cardiomyovasculopathy among patients with acute coronary syndrome.

Prevalence of triglyceride deposit cardiomyovasculopathy among patients with acute coronary syndrome.

Comparison of calculation algorithms between arithmetic mean of washout rate and total-count-based washout rate in single-photon emission computed tomography

Abstract Background Myocardial washout rate (WR) analysis of radiopharmaceuticals is utilized in nuclear cardiology to evaluate the clinical pathophysiology of the heart. WR is defined as the ratio of the difference between the count in the early image and the time-decay-corrected delayed image divided by the former. The arithmetic mean of washout rate (AMWR) of each segment is a commonly used algorithm for calculating WR from a polar map in single-photon emission computed tomography (SPECT). However, in this algorithm, uneven radiotracer uptake among segments affects WR calculation. Therefore, we newly formulated a modified algorithm for calculating WR based on the total count (TCWR). Purpose To clarify the usefulness of TCWR by comparing the calculation algorithms between TCWR and AMWR. Methods The WR of iodine-123-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) was calculated using TCWR and AMWR, and WR values using TCWR and AMWR were compared by disease. We focused on the patients with specific conditions that decreased BMIPP uptake in the early image — CD36 deficiency is a human loss-of-function genetic mutation model for BMIPP uptake, and old myocardial infarction (OMI) may present such a clinical phenotype. Also, patients with triglyceride deposit cardiomyovasculopathy (TGCV) were enrolled since a markedly decreased BMIPP WR (<10%) is one of the essential criteria for its diagnosis. Consecutive patients who underwent BMIPP scintigraphy were reviewed, and the analysis included patients without detectable cardiovascular diseases (normal) (n = 11), those with CD36 deficiency (n = 6), TGCV (n = 14), TGCV with OMI (n = 17), and non-TGCV with OMI (n = 10). Results WR values using TCWR and AMWR did not differ significantly in the following groups: normal, 27.4 ± 8.5 and 27.3 ± 8.5% (p = 0.97); CD36 deficiency, -3.2 ± 6.5 and -4.1 ± 7.4% (p = 0.81); TGCV, 2.4 ± 6.3 and 2.2 ± 6.3% (p = 0.93); and TGCV with OMI, -0.9 ± 7.6 and -3.7 ± 8.4% (p = 0.32). However, AMWR showed a lower WR than TCWR in non-TGCV with OMI (4.8 ± 8.7 and 18.9 ± 6.7%, p = 0.0008). Conclusions TCWR is suitable for calculating WR using SPECT polar maps even in cases with heterogeneous radiotracer uptake, such as OMIs. TCWR may be applied to measuring the WR of radiopharmaceuticals other than BMIPP in investigating the pathophysiology of heart diseases.Definition of calculation algorithms.Comparison of TCWR and AMWR.

Abstract 14505: BSCL2/Seipin Deletion Rescues ATGL-Deficiency-Induced Lethal Lipotoxic Cardiomyopathy

Imbalances in triglyceride (TG) catabolism are associated with cardiac lipid deposition and contractile dysfunction, as manifested in patients with primary triglyceride deposit cardiomyovasculopathy (TGCV) caused by adipose triglyceride lipase (ATGL) deficiency. BSCL2/Seipin is a highly conserved endoplasmic reticulum protein widely implicated in lipid droplet biogenesis and TG metabolism. We previously reported that global Bscl2 –/– mice and mice with cardiac-specific deletion of Bscl2 manifest higher myocardial ATGL expression and develop mild cardiomyopathy with reduced cardiac steatosis. However, the interplay between BSCL2 and ATGL in hearts remains to be further interrogated. In this study, we surprisingly discovered that global BSCL2 deletion completely rescued the lethal lipotoxic cardiomyopathy in the genetic ATGL-deficient TGCV model ( Atgl –/– mice) by drastically reducing cardiac TG deposits, abolishing cardiac hypertrophy, and restoring cardiac contractility. Transcriptomic analyses identified the elevated inflammatory, oxidative stress, and extracellular matrix pathways in Atgl –/– hearts, which were dramatically ameliorated by BSCL2 deletion. Conversely, the severely suppressed cardiac metabolic functions, muscle contraction, and ion transport pathways in Atgl –/– hearts were also normalized by BSCL2 deletion. Heatmap data further revealed that the mRNA levels of Pgc1/Ppara and fatty acid oxidation (FAO) genes were not altered in Bscl2 –/– hearts but were severely repressed in Atgl –/– hearts due to defective TG lipolysis. However, their expressions in Atgl –/– Bscl2 –/– hearts were restored to similar levels as wild-type and Bscl2 –/– hearts. RT-PCR analyses further confirmed such changes. Notably, cardiac-specific deletion of BSCL2 rescues lethal cardiomyopathy in mice with cardiac-specific deletion of ATGL. These data suggest that cardiac BSCL2 cell-autonomously regulates ATGL-independent TG hydrolysis and FAO pathways essential for cardiac function. Our study highlights the presence of BSCL2-mediated ATGL-independent pathways that regulate cardiac TG metabolism and provide novel therapeutic approaches to treat ATGL-deficiency-associated lethal cardiomyopathy.

1H-MRS to evaluate improved triglyceride accumulation in idiopathic triglyceride deposit cardiomyovasculopathy after CNT-01 (tricaprin/trisdecanion) administration.

Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride (TG) accumulation in the myocardium and coronary arteries caused by genetic or acquired dysfunction of adipose TG lipase (ATGL). A phase IIa trial has been conducted involving patients with idiopathic TGCV using CNT-01 (tricaprin/trisdecanion) by the Japan TGCV study group, which showed that CNT-01 improved myocardial lipolysis as demonstrated by iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) scintigraphy. We evaluated changes in myocardial TG content using proton magnetic resonance spectroscopy (1H-MRS) before/after CNT-01. This report describes a male patient with hypertension, diabetes, angina pectoris, repeated percutaneous coronary intervention, chest pain, and exertional dyspnea that persisted despite standard medications and nitroglycerin. Idiopathic TGCV was diagnosed based on a remarkably reduced washout rate (WR) for BMIPP scintigraphy, high myocardial TG content on 1H-MRS, and no ATGL mutation. After an 8-week, 1.5 g/day CNT-01 administration, the WR of BMIPP increased from 5.1 to 13.3% and the myocardial TG content decreased from 8.4 to 5.9%, with no adverse effects. CNT-01 corrected myocardial lipolysis and subsequently reduced TG content in idiopathic TGCV as evaluated using 1H-MRS, which may be a useful, noninvasive evaluation of therapeutic efficacy. Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride accumulation in the myocardium and coronary arteries, caused by genetic or acquired dysfunction of adipose triglyceride lipase. Japan TGCV Study Group developed a specific treatment for idiopathic TGCV using CNT-01 (tricaprin/trisdecanion), a type of medium-chain fatty acid. CNT-01 corrected myocardial lipolysis and reduced TG content in idiopathic TGCV using proton magnetic resonance spectroscopy, which may be a useful noninvasive evaluation of therapeutic efficacy.

Additional diagnostic value of electron microscopic examination in endomyocardial biopsy in patients with suspected non-ischemic cardiomyopathy

BackgroundElectron microscopy enables a finely detailed analysis of ultra-structural features, and hence, it generally has an added diagnostic value to light microscopy alone. However, no studies have verified the additional diagnostic value of electron microscopic examination in patients with suspected non-ischemic cardiomyopathy. MethodsA total of 294 consecutive patients with non-ischemic cardiomyopathy who underwent endomyocardial biopsy were prospectively enrolled. Patients were divided into three groups according to left ventricular morphology assessed using echocardiography. Myocardial specimens were collected from the right ventricular septum and examined by light microscopy. Electron microscopy was performed subsequently to evaluate the additional diagnostic value. ResultsAltogether, 294 patients were analyzed, including 160 (55 %), 96 (33 %), and 35 (12 %) patients who were diagnosed with primary, secondary, and unclassified cardiomyopathy, respectively. In patients with dilated cardiomyopathy-like morphology, the detection rate of disease-specific histological findings was relatively low compared to that in patients with other cardiac morphologies. The additional diagnostic value of electron microscopy was observed in eight patients, including five with Fabry disease, one with cardiac amyloidosis, one with mitochondrial cardiomyopathy, and one with triglyceride deposit cardiomyovasculopathy. Among the 18 cardiac amyloidosis cases, electron microscopy detected amyloid fibrils in all patients, whereas light microscopy could not detect amyloid deposition in 1 patient. Among one of five patients with Fabry disease, light microscopy did not show obvious vacuolated cardiomyocytes, but zebra bodies were detected by electron microscopy, leading to the diagnosis of cardiac Fabry disease. The diagnostic value of electron microscopic examination in patients with cardiac sarcoidosis was not observed. ConclusionsThe additional diagnostic value of electron microscopy was observed in patients with secondary cardiomyopathy, in whom light microscopy did not show disease-specific histological findings. Electron microscopy should be performed in cases where secondary cardiomyopathy is strongly suspected with no disease-specific findings by light microscopy.

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

ObjectiveThis study aimed to optimize various methods of calculating washout rates (WRs) of 123I-β-methyl-p-iodophenyl-pentadecanoic (BMIPP), as they are essential to diagnose triglyceride deposit cardiomyovasculopathy (TGCV) which is a rare disease entity identified in Japan and has been encoded in Orphanet (ORPHA code 565612).MethodsWe calculated WRs of 123I-BMIPP from early (20 min) and delayed (200 min) images. We evaluated six methods of calculating WRs to discriminate TGVC patients (age, 56.8 ± 14.6 y; male, n = 13; female, n = 4) and 21 123I-BMIPP studies were involved including 4 follow-up studies. Washout rates were calculated by two planar methods using anterior images with cardiac and background regions of interest (ROIs) and by four SPECT methods using either array and polar plots or summed short-axis images. The final diagnoses of TGCV were confirmed according to the 2020 diagnostic criteria, and the diagnostic accuracy of WRs calculated using the six methods was analyzed using the area under receiver-operating characteristics curves (ROC-AUC). Multiple scatter-plot matrix methods were evaluated with correlations for comparison.ResultsAll six methods were useful for diagnosis and did not significantly differ. The four SPECT methods showed excellent diagnostic accuracy (AUC 1.0), whereas the planar methods with and without background correction could be acceptable (AUC 0.857 and 0.964, respectively). The WRs were relatively lower for patients with CAD and remarkable metabolic defects than for patients with TGCV but without defects.ConclusionsFor the diagnosis of TGCV, the WR cutoff of 10% of 123I-BMIPP functioned well in planar and SPECT discrimination based on computational methods as a classifier. However, calculation optimization should improve TGCV diagnoses.

Clinical significance of 123I-BMIPP washout rate in patients with uncertain chronic heart failure.

Recently, triglyceride deposit cardiomyovasculopathy (TGCV) with defective intracellular lipolysis was found to be a disease that causes heart failure. As a diagnostic criterion for TGCV, an Iodaine-123-β-methyl iodophenyl-pentadecanoic acid washout rate (BMIPP WOR) of < 10% is used, but its clinical significance in patients with heart failure remains to be clarified. In 62 hospitalized patients with chronic heart failure, 123I-BMIPP myocardial single-photon emission computed tomography (SPECT) was performed predischarge state. The prevalence of TGCV was investigated. Subsequently, follow-up was conducted for ≥ 90days (mean: 724.6 ± 392.7days), and the association between the BMIPP WOR and cardiac events was examined, establishing all-cause mortality and admission due to heart failure as endpoints. Of the 62 patients, the WOR was < 10% in 41 (66.1%). Of these, 26 (41.9%) were diagnosed with definite TGCV. Furthermore, cardiac events were noted in 12 patients (19.4%). Analysis with Cox proportional hazards models showed that the BMIPP WOR < 4.5% was a significant event-predicting factor [HR 4.29, 95% CI: 1.20-16.87; p = 0.0245]. On a Kaplan-Meier curve, the WOR was 4.5%; there was a significant difference in the incidence of events (p = 0.0298). In the predischarge state of heart failure, 123I-BMIPP myocardial SPECT was performed. In approximately 40% of the patients, a diagnosis of TGCV was made. The results suggested that the BMIPP WOR is useful for predicting the prognosis of chronic heart failure patients regardless of TGCV.

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

Background: The arithmetic mean of washout rate (WR) (namely, AMWR) of each segment is a commonly used algorithm for calculating WR from a polar map in single-photon emission computerized tomography (SPECT). However, in this algorithm, uneven radiotracer uptake among segments affects WR calculation. To solve this possible issue, we formulated a modified algorithm for calculating WR based on the total count (namely, TCWR). Methods: The WR of iodine-123-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) was calculated using TCWR and AMWR, and WR values using TCWR and AMWR were compared by disease. Participants included those without cardiovascular diseases (normal), those with CD36 deficiency, triglyceride deposit cardiomyovasculopathy (TGCV), TGCV with old myocardial infarction (OMI), and non-TGCV with OMI. Results: WR values using TCWR and AMWR did not differ significantly in the following groups: normal, 27.4±8.5 and 27.3±8.5% (p=0.97); CD36 deficiency, -3.2±6.5 and -4.1±7.4% (p=0.81); TGCV, 2.4±6.3 and 2.2±6.3% (p=0.93); and TGCV with OMI, -0.9±7.6 and -3.7±8.4% (p=0.32). However, AMWR showed a lower WR than TCWR in non-TGCV with OMI (4.8±8.7 and 18.9±6.7%, p=0.0008). Conclusions: TCWR is suitable for calculating WR using SPECT polar maps even in cases with heterogeneous radiotracer uptake, such as OMIs. TCWR may be applied to measuring the WR of radiopharmaceuticals other than BMIPP in investigating the pathophysiology of heart diseases.

123I-BMIPP Scintigraphy Shows That CNT-01 (Tricaprin) Improves Myocardial Lipolysis in Patients with Idiopathic Triglyceride Deposit Cardiomyovasculopathy: First Randomized Controlled, Exploratory Trial for TGCV.

Background: Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare intractable cardiovascular disorder (Orphanet ORPHAcode: 565612) in which defective intracellular lipolysis results in heart failure and coronary artery disease. Myocardial scintigraphy with 123I-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) is useful to evaluate myocardial TG metabolism; its washout rate (WR) reflects myocardial lipolysis. This study reports the effects of CNT-01 (tricaprin), a developing orphan drug to facilitate lipolysis, on BMIPP-WR in patients with TGCV. Methods: An investigator-initiated, multicenter, randomized, double-blind exploratory, trial (Phase IIa) was conducted (UMIN000035403). Seventeen patients with idiopathic TGCV were orally administered 1.5 g/day of CNT-01 or placebo for 8 weeks. Endpoints included delta BMIPP-WR and clinical parameters such as 6-minwalk distance and TGCV severity score. Results: During the protocol, delta BMIPP-WRs were -0.26±3.28 and 7.08±3.28% (95% confidence intervals, -7.36 to 6.84 and -0.01 to 14.18) in the placebo and CNT-01 groups, respectively. The baseline-adjusted difference of delta BMIPP-WR between the two groups was significant (p=0.035) after one patient was excluded from the placebo group because of pseudonormalization of BMIPP-WR related to coronary bypass graft stenosis. Clinical parameters did not show significant changes. Conclusions: This study proved the mechanism of CNT-01 to improve myocardial lipolysis in TGCV, as demonstrated by BMIPP scintigraphy.

Abstract 11038: One Year Prognosis After Coronary Intervention in Hemodialysis Patients Accompanied with Triglyceride Deposit Cardiomyovasculopathy, a Novel Type Atherosclerosis with Triglyceride Deposition

Introduction: Triglyceride deposit cardiomyovasculopathy (TGCV) patients presents the massive accumulation of triglyceride in smooth muscle cells characterized by a novel diffuse narrowing atherosclerosis. There are reported prognostic data on hemodialysis cases accompanied with TGCV, however, little prognostic data after coronary intervention are known. Hypothesis: There might be poor prognosis after coronary intervention in hemodialysis patients accompanied with TGCV. Methods: This retrospective single-center observational study included data from the cardiac catheter database at the study institution between April 2011 and March 2017. Among 654 consecutive patients on hemodialysis, the data for 36 patients implanted DES who could be collated the diagnostic criteria for TGCV using both 123I-β-methyl-iodophenyl- pentadecanoic acid scintigraphy and coronary angiography were analysed. Patients were divided into two groups (TGCV or non-TGCV control group). One-year prognosis after coronary intervention in patients accompanied with and without TGCV were studied. Results: The cohort included 13 and 23 patients accompanied with and without TGCV, respectively. Figure showed one-year prognosis, composite of cardiovascular death or non-fatal myocardial infarction or urgent revascularization, between two groups. Incidence of composite events after coronary intervention was higher in the TGCV group than in the control group (log-rank p=0.036). TGCV was a significantly and independently associated with one-year prognosis after coronary intervention even after adjusted confounding factors. Conclusions: These results demonstrated that TGCV comorbidity is associated with poor prognosis after coronary intervention in hemodialysis patients, and contributes to the novel risk factor for coronary intervention.

Abstract 12811: Clinical Outcomes and Prognostic Impact of Triglyceride Deposit Cardiomyovasculopathy Among Hemodialysis Patients Suspected of Coronary Artery Disease

Introduction: Hemodialysis (HD) has been reported as a strong prognostic factor in patients with cardiovascular disease. It is unknown how much triglyceride deposit cardiomyovasculopathy (TGCV), a novel identified rare cardiovascular disorder, is associated with cardiovascular mortality among HD patients. Hypothesis: We hypothesized that comorbidity of TGCV in HD patients who suspected of CAD plays a critical role for cardiovascular outcomes in this population. Methods: We examined the data obtained from 83 consecutive HD patients suspected of coronary artery disease who underwent both [123I]-β-methyl-iodophenyl-pentadecanoic acid (BMIPP) scintigraphy and subsequent coronary angiography (CAG). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke up to 5 years of follow-up. The key secondary endpoint was a composite of cardiovascular death, non-fatal MI, non-fatal stroke, target vessel revascularization, or any hospitalization for heart failure. Results: A total of 83 HD patients were grouped into either the definite TGCV (17 patients), the probable TGCV (22 patients), or the non-TGCV control group (44 patients). At the end of the follow-up period for a median of 4.7 years, a primary endpoint event occurred in 58.8% of the definite TGCV patients (hazard ratio, 8.06; 95% confidence interval [CI], 2.52-25.8, Log-rank p&lt;0.001) and 27.3% of the probable TGCV patients, as compared to 9.1% of the non-TGCV control patients; the corresponding rates of the key secondary endpoint were 88.2% for the definite TGCV patients (hazard ratio, 6.36; 95% CI, 2.89-14.0, Log-rank p&lt;0.001) and 59.1% for the probable TGCV patients. In the multivariate Cox proportional hazard analyses after adjustment for confounding factors, various variables related to mortality on HD patients, or variables known as a classical cardiovascular risk, the definite TGCV was significantly and independently associated with cardiovascular mortality and outcomes in any of the three models. Conclusions: Comorbidity of TGCV in patients on HD was associated with increased risk of cardiovascular events including cardiovascular death, which might highlight the potential therapeutic target.

Prevalence and clinical outcomes of triglyceride deposit cardiomyovasculopathy among haemodialysis patients

ObjectiveTo evaluate the effect of triglyceride deposit cardiomyovasculopathy (TGCV) on the cardiovascular outcomes in haemodialysis (HD) patients with suspected coronary artery disease (CAD).MethodsThis retrospective single-centre observational study included data from...

Association of Triglyceride Deposit Cardiomyovasculopathy With Drug-Eluting Stent Restenosis Among Patients With Diabetes

This cohort study uses data from a single-center cardiac catheter database to investigate the association of cardiac stent restenosis in patients with diabetes mellitus and comorbid triglyceride deposit cardiomyovasculopathy.

Correlation Perspectives for the Diagnosis of Idiopathic Triglyceride Deposit Cardiomyovasculopathy

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.

The Diagnostic Criteria 2020 for Triglyceride Deposit Cardiomyovasculopathy.

Triglyceride deposit cardiomyovasculopathy (TGCV) is a newly identified disease that was discovered in individuals who required cardiac transplantation in Japan in 2008. Defective intracellular lipolysis causes triglyceride (TG) accumulation in the myocardium and coronary artery vascular smooth muscle cells, which results in severe heart failure and coronary artery disease with poor prognosis. A known cause of TGCV is a genetic deficiency of adipose triglyceride lipase (ATGL), a rate-limiting enzyme in the intracellular hydrolysis of TG. TGCV is classified into primary TGCV with ATGL mutations and idiopathic TGCV without ATGL mutations. Since its discovery, the Japan TGCV Study Group has attempted to elucidate its pathophysiology, develop diagnostic procedures, and specific treatment. Myocardial scintigraphy with iodine-123-β-methyl iodophenyl-pentadecanoic acid (123I-BMIPP) is a unique imaging modality for evaluating myocardial lipolysis in vivo. The washout rate of 123I-BMIPP is an essential indicator for the diagnosis of TGCV. Along with our efforts to provide awareness of and insights into this disease concept, we found that the cumulative number of clinically diagnosed patients has reached >200 and the cases are distributed throughout Japan. In addition, we successfully completed three investigator-initiated clinical trials of a potential therapeutic agent (CNT-01) for TGCV, which was assigned by the Ministry of Health, Labour, and Welfare, Japan, under the SAKIGAKE Designation System in June 2020. Here, we provide the Diagnostic Criteria 2020 for TGCV in order to further promote this "rare and intractable disease" project.

Effect of Tricaprin on Cardiac Proteome in a Mouse Model for Triglyceride Deposit Cardiomyovasculopathy

Triglyceride deposit cardiomyovasculopathy (TGCV), a rare cardiovascular disorder caused by genetic or acquired dysfunction of adipose triglyceride lipase (ATGL), is marked by defective intracellular lipolysis that results in excessive accumulation of triglycerides (TGs) in the myocardium and coronary arteries, leading to intractable heart failure (HF). We have developed a specific treatment for TGCV using tricaprin, a medium chain TG, as part of a governmental rare disease project in Japan. We recently reported that tricaprin diet improved cardiac TG metabolism and left ventricular function in an ATGL-knockout (KO) mouse, a mouse model for TGCV. Here, we report the effect of tricaprin on the myocardial proteome of KO mice to elucidate the mechanisms of action of tricaprin at protein expression levels. We compared proteomic changes in the hearts of KO mice fed control or tricaprin diet. Tandem mass tag-based shotgun proteomics identified 1832 proteins common to all sample groups. Whole proteomic distribution in the heart was largely up-regulated in KO mice fed control diet. When using cut-off values (>1.5 or <0.67, FDR-adjusted p value<0.01), in fact, 65 proteins were up-regulated whereas only 2 proteins were down-regulated in the hearts of KO mice fed control diet. The former included proteins assigned to "Cardiac Arrhythmia", and "Cardiac Damage" reflecting HF by a toxicity function analysis. One of the latter was Ces1d, which is known to regulate intracellular TG metabolism. These proteomic changes observed in KO mice were dramatically rescued by the tricaprin diet. These results indicated that tricaprin diet ameliorated HF in a TGCV mouse model at protein expression levels and also provided important clues to understand mechanisms for the beneficial effect of tricaprin.

P2688A novel risk factor of stent restenosis after drug-eluting stent implantation; Involvement of triglyceride deposit cardiomyovasculopathy, coronary atherosclerosis with triglyceride deposition

Abstract Background Triglyceride deposit cardiomyovasculopathy (TGCV) is a novel disease concept characterized by the excessive accumulation of triglyceride in cardiomyocytes and vascular smooth muscle cells, leading to coronary artery disease (CAD), heart failure, and arrhythmia. However, it is rarely known whether TGCV contributes to the increased risk of vascular failure after drug eluting stent (DES) implantation. Purpose The aim of this study was to evaluate vascular failure after 2nd generation DES implantation in patients with TGCV. Methods Among 637 consecutive patients suspected of having CAD who underwent both coronary angiography and iodine-123-β-methyliodophenyl-pentadecanoic acid (BMIPP) scintigraphy between 2010 and 2018, we analyzed the data from 92 patients who met the inclusion criteria (shown in Table and Figure). Ninety-two patients were allocated to the presence (TGCV group, 11 patients) or absence (control group, 81 patients) of TGCV. All of 92 patients were implanted 2nd generation DES and underwent planned follow up coronary angiography. Control patients were diagnosed of diabetes mellitus. Binary restenosis (ISR), defined as angiographic luminal diameter ≥50% by quantitative coronary angiography, target lesion revascularization (TLR), In-stent late loss and restenosis morphology were assessed in 23 stents of TGCV group and 120 stents of control group. Results There were no significant differences in baseline characteristics between the two groups except for the prevalence of hypertension. In-stent late loss was greater in TGCV than in control (0.45 (−0.04 to 3.33) vs. 0.15 (−0.18 to 2.75), p=0.ehz748.10067), resulting in greater incidence of ISR and TLR in TGCV than in control (34.8% vs. 10.0%, p=0.0017; 21.7% vs. 6.7%, p=0.021, respectively). On multivariable logistic regression analysis, TGCV was found to be a significant and independent predictor for ISR after 2nd generation DES implantation. Regarding restenosis morphology, diffuse and occlusive pattern of ISR, were more frequently observed in TGCV than control (87.5% and 33.3%, Fisher's exact test p=0.028). Table 1.The 4th edition diagnostic criteria for TGCV Items Clinical findings 2 points I) BMIPP scintigraphy Wash-Out Rare &lt;10% II) Diffuse narrowng coronary arteries 1 point III) Jordans anomaly in peripheral blood smear IV) Diabetes Decision 4 points or more → Definite TGCV Figure 1 Conclusion Patients with TGCV showed the greater incidence of vascular failure even after 2nd generation DES implantation, contributing to the novel risk factor for coronary intervention even in the 2nd DES era.

P1662Impact of triglyceride deposit cardiomyovasculopathy, a novel type atherosclerosis with triglyceride deposition in coronary arteries, on neointimal proliferation after coronary stent-implantation

P1662Impact of triglyceride deposit cardiomyovasculopathy, a novel type atherosclerosis with triglyceride deposition in coronary arteries, on neointimal proliferation after coronary stent-implantation