Association of Triglyceride Deposit Cardiomyovasculopathy With Drug-Eluting Stent Restenosis Among Patients With Diabetes.
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ABSTRACT:
SUBMITTER: Nakano Y
PROVIDER: S-EPMC7414388 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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Association of Triglyceride Deposit Cardiomyovasculopathy With Drug-Eluting Stent Restenosis Among Patients With Diabetes.
Nakano Yusuke Y Suzuki Mayu M Hirano Ken-Ichi KI Ando Hirohiko H Takashima Hiroaki H Takahashi Hiroshi H Amano Tetsuya T
JAMA network open 20200803 8
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Project description: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.
| S-EPMC10133930 | biostudies-literature
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| S-EPMC10927025 | biostudies-literature
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| S-EPMC10067465 | biostudies-literature
Project description:Given the limited salvage options for in-stent restenosis (ISR) of drug-eluting stents (DES), our high-volume cardiac catheterization laboratory has been performing intracoronary brachytherapy (ICBT) in patients with recurrent ISR of DES. This study analyzes their baseline characteristics and assesses the safety/toxicity of ICBT in this high-risk population.A retrospective analysis of patients treated with ICBT between September 2012 and December 2014 was performed. Patients with ISR twice in a single location were eligible. Procedural complications included vessel dissection, perforation, tamponade, slow/absent blood flow, and vessel closure. Postprocedural events included myocardial infarction, coronary artery bypass graft, congestive heart failure, stroke, bleeding, thrombosis, embolism, dissection, dialysis, or death occurring within 72 hours. A control group of patients with 2 episodes of ISR at 1 location who underwent percutaneous coronary intervention without ICBT was identified. Unpaired t tests and χ2 tests were used to compare the groups.There were 134 (78%) patients in the ICBT group with 141 treated lesions and 37 (22%) patients in the control group. There was a high prevalence of hyperlipidemia (>95%), hypertension (>95%), and diabetes (>50%) in both groups. The groups were well-balanced with respect to age, sex, and pre-existing medical conditions, with the exception of previous coronary artery bypass graft being more common the ICBT group. Procedural complication rates were low in the control and ICBT groups (0% vs 4.5%, P = .190). Postprocedural event rates were low (<5%) in both groups. Readmission rate at 30 days was 3.7% in the ICBT group and 5.4% in the control group (P = .649).This is the largest recent known series looking at ICBT for recurrent ISR of DES. ICBT is a safe treatment option with similarly low rates (<5%) of procedural and postprocedural complications compared with percutaneous coronary intervention alone. This study establishes the safety of ICBT in a high-risk patient cohort.
| S-EPMC5506705 | biostudies-other
Project description:BackgroundTriglyceride deposit cardiomyovasculopathy (TGCV) is a rare disease, characterized by the massive accumulation of triglyceride (TG) in multiple tissues, especially skeletal muscle, heart muscle and the coronary artery. TGCV is caused by mutation of adipose triglyceride lipase, which is an essential molecule for the hydrolysis of TG. TGCV is at high risk for skeletal myopathy and heart dysfunction, and therefore premature death. Development of therapeutic methods for TGCV is highly desirable. This study aims to discover specific molecules responsible for TGCV pathogenesis.MethodsTo identify differentially expressed proteins in TGCV patient cells, the stable isotope labeling with amino acids in cell culture (SILAC) method coupled with LC-MS/MS was performed using skin fibroblast cells derived from two TGCV patients and three healthy volunteers. Altered protein expression in TGCV cells was confirmed using the selected reaction monitoring (SRM) method. Microarray-based transcriptome analysis was simultaneously performed to identify changes in gene expression in TGCV cells.ResultsUsing SILAC proteomics, 4033 proteins were quantified, 53 of which showed significantly altered expression in both TGCV patient cells. Twenty altered proteins were chosen and confirmed using SRM. SRM analysis successfully quantified 14 proteins, 13 of which showed the same trend as SILAC proteomics. The altered protein expression data set was used in Ingenuity Pathway Analysis (IPA), and significant networks were identified. Several of these proteins have been previously implicated in lipid metabolism, while others represent new therapeutic targets or markers for TGCV. Microarray analysis quantified 20743 transcripts, and 252 genes showed significantly altered expression in both TGCV patient cells. Ten altered genes were chosen, 9 of which were successfully confirmed using quantitative RT-PCR. Biological networks of altered genes were analyzed using an IPA search.ConclusionsWe performed the SILAC- and SRM-based identification-through-confirmation study using skin fibroblast cells derived from TGCV patients, and first identified altered proteins specific for TGCV. Microarray analysis also identified changes in gene expression. The functional networks of the altered proteins and genes are discussed. Our findings will be exploited to elucidate the pathogenesis of TGCV and discover clinically relevant molecules for TGCV in the near future.
| S-EPMC3891998 | biostudies-literature
Project description:BackgroundThe triglyceride-glucose (TyG) index is an alternative marker of insulin resistance (IR) and is closely associated with the prevalence and prognosis of atherosclerotic cardiovascular disease (ASCVD). However, the association between the TyG index and in-stent restenosis (ISR) after drug-eluting stent (DES) implantation in patients with acute coronary syndrome (ACS) remains unknown.MethodsThe present study retrospectively recruited patients who were admitted for ACS and underwent coronary angiography at 6 to 24 months after successful DES-based percutaneous coronary intervention (PCI). In addition, we calculated the TyG index with the following formula: Ln(fasting triglyceride [mg/dL] × fasting blood glucose [mg/dL]/2) and divided patients into 3 groups according to the tertile of the TyG index. Most importantly, multivariate logistic regression analysis models were also constructed to assess the association between the TyG index and DES-ISR in patients with ACS.ResultsA total of 1574 patients with ACS (58.4 ± 9.4 years, 77.4% male) were included in this study. At the median follow-up time of 12 (9-14) months, the prevalence of DES-ISR increased stepwise with the increasing tertile of the TyG index (11.6% vs 17.3% vs 19.4%, p = 0.002), and the TyG index was also higher in the ISR group than in the non-ISR group (9.00 ± 0.58 vs 8.84 ± 0.61, p < 0.001). In addition, the positive association between the TyG index and the prevalence of DES-ISR was also determined in the fully adjusted model (TyG, per 1-unit increase: OR 1.424, 95% CI 1.116 to 1.818, p = 0.005; tertile of TyG, the OR (95% CI) values for tertile 2 and tertile 3 were 1.454 (1.013 to 2.087) and 1.634 (1.125 to 2.374), respectively, with tertile 1 as a reference). The association was also reflected in most subgroups. Moreover, adding the TyG index to the predictive model for DES-ISR in patients with ACS could contribute to an increase in C-statistics (0.675 vs 0.659, p = 0.010), categorical net reclassification improvement (0.090, p < 0.001), and integrated discrimination improvement (0.004, p = 0.040).ConclusionAn elevated TyG index was independently and positively associated with DES-ISR in patients with ACS who underwent PCI. However, the incremental predictive value of the TyG index for DES-ISR was slight. To further confirm our findings, future studies are needed.
| S-EPMC8268452 | biostudies-literature
Project description:BackgroundAlthough drug-eluting stents (DES) have reduced the rates of in-stent restenosis (ISR) compared with bare-metal stents (BMS), DES related ISR (DES-ISR) still occurs and outcomes of DES-ISR remain unclear. The objective of this meta-analysis was to investigate the long-term clinical outcomes of patients with DES-ISR compared with patients with BMS related ISR (BMS-ISR) after the treatment of DES or drug-eluting balloon (DEB). Methods and results. We searched the literature in the main electronic databases including PUBMED, EMBASE, Cochrane Library, and Web of Science. The primary endpoints were target lesion revascularization (TLR) and target vessel revascularization (TVR). The secondary endpoints included all cause death (ACD), cardiac death (CD), myocardial infarction (MI), stent thrombosis or re-in-stent restenosis (ST/RE-ISR), and major adverse cardiovascular events (MACEs). A total of 19 studies with 6256 participants were finally included in this meta-analysis. Results showed that the rates of TLR (P < 0.00001), TVR (P < 0.00001), CD (P=0.02), ST/RE-ISR (P < 0.00001), and MACEs (P < 0.00001) were significantly higher in the DES-ISR group than in the BMS-ISR group. No significant differences were found between the two groups in the rates of MI (P=0.05) and ACD (P=0.21).ConclusionsOur study demonstrated that patients with DES-ISR had worse clinical outcomes at the long-term follow-up than patients with BMS-ISR after the treatment of DES or DEB, suggesting that DES and DEB may be more effective for BMS-ISR than that for DES-ISR. Positive prevention of DES-ISR is indispensable and further studies concentrating on detecting the predictors of outcomes of DES-ISR are required.
| S-EPMC7336236 | biostudies-literature
Project description:BackgroundCurrently, drug-eluting balloon (DEB) appears to be an attractive alternative option for the treatment of in-stent restenosis (ISR). Nevertheless, the clinical outcomes of DEB have seldom been compared to those of new-generation drug-eluting stent (DES). Thus, this meta-analysis aimed to evaluate the safety and efficacy of DEB compared to those of new-generation DES in the treatment of ISR.MethodsA comprehensive search of electronic databases including PubMed, EMBASE, and Cochrane Library up to November 2, 2017 was performed to identify pertinent articles comparing DEB to new-generation DES for the treatment of ISR. In addition, conference proceedings for the scientific sessions of the American College of Cardiology, American Heart Association, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, and EuroPCR were also searched. The primary endpoint was target lesion revascularization (TLR) at the longest follow-up. Dichotomous variables were presented as risk ratios (RR s) with 95% confidence intervals (CI s), while the overall RR s were estimated using the Mantel-Haenszel random-effects model.ResultsFive randomized controlled trials (RCTs) and eight observational studies involving 2743 patients were included in the present meta-analysis. Overall, DEB was comparable to new-generation DES in terms of TLR (RR = 1.24, 95% CI: 0.89-1.72, P = 0.21), cardiac death (RR = 1.55, 95% CI: 0.89-2.71, P = 0.12), major adverse cardiovascular event (RR = 1.21, 95% CI: 0.98-1.48, P = 0.07), myocardial infarction (RR = 1.12, 95% CI: 0.72-1.76, P = 0.62), and stent thrombosis (RR = 0.95, 95% CI: 0.38-2.42, P = 0.92). However, DEB was associated with higher risk of all-cause mortality than new-generation DES (RR = 1.65, 95% CI: 1.09-2.50, P = 0.02). This was especially true in the real-world observational studies (RR = 1.79, 95% CI: 1.12-2.88, P = 0.02). In RCTs, however, no significant difference was found between the two treatment strategies in the risk of all-cause mortality.ConclusionsThe current meta-analysis showed that DEB and new-generation DES had comparable safety and efficacy for the treatment of ISR in RCTs. However, treatment with DEB was associated with higher risk of all-cause mortality in the real-world nonrandomized studies.
| S-EPMC5850679 | biostudies-literature
Project description:BackgroundGood results of drug-eluting balloon (DEB) use are achieved in in-stent restenosis (ISR) lesions, small vessel disease, long lesions, and bifurcations. However, few reports exist about DEB use in acute myocardial infarction (AMI) with ISR. This study's aim was to evaluate the efficacy of DEB for AMI with ISR.MethodsBetween November 2011 and December 2015, 117 consecutive patients experienced AMI including ST-segment elevation MI, and non-ST-segment elevation MI due to ISR, and received percutaneous coronary intervention (PCI). We divided our patients into two groups: (1) PCI with further DEB, and (2) PCI with further drug-eluting stent (DES). Clinical outcomes such as target lesion revascularization, target vessel revascularization, recurrent MI, stroke, cardiovascular mortality, and all-cause mortality were analyzed.ResultsThe patients' average age was 68.37 ± 11.41 years; 69.2% were male. A total of 75 patients were enrolled in the DEB group, and 42 patients were enrolled in the DES group. The baseline characteristics between the two groups were the same without statistical differences except for gender. Peak levels of cardiac biomarker, pre- and post-PCI cardiac function were similar between two groups. The major adverse cardiac cerebral events rate (34.0% vs. 35.7%; p = 0.688) and cardiovascular mortality rate (11.7% vs. 12.8%; p = 1.000) were similar in both groups.ConclusionsDEB is a reasonable strategy for AMI with ISR. Compared with DES, DEB is an alternative strategy which yielded acceptable short-term outcomes and similar 1-year clinical outcomes.
| S-EPMC5910788 | biostudies-literature
Project description:As the rate of percutaneous coronary intervention increases, in-stent restenosis (ISR) has become a burden. Random forest (RF) could be superior to logistic regression (LR) for predicting ISR due to its robustness. We developed an RF model and compared its performance with the LR one for predicting ISR. We retrospectively included 1501 patients (age: 64.0 ± 10.3; male: 76.7%; ISR events: 279) who underwent coronary angiography at 9 to 18 months after implantation of 2nd generation drug-eluting stents. The data were randomly split into a pair of train and test datasets for model development and validation with 50 repeats. The predictive performance was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC). The RF models predicted ISR with larger AUC-ROCs of 0.829 ± 0.025 compared to 0.784 ± 0.027 of the LR models. The difference was statistically significant in 29 of the 50 repeats. The RF and LR models had similar sensitivity using the same cutoff threshold, but the specificity was significantly higher in the RF models, reducing 25% of the false positives. By removing the high leverage outliers, the LR models had comparable AUC-ROC to the RF models. Compared to the LR, the RF was more robust and significantly improved the performance for predicting ISR. It could cost-effectively identify patients with high ISR risk and help the clinical decision of coronary stenting.
| S-EPMC9126385 | biostudies-literature