Atherosclerosis often results in high incidence of vascular occlusion and has been recognized as the major cause of coronary artery disease. We had previously reported that promoter polymorphism of ...myocardin-related transcription factor A (MRTF-A) is associated with coronary atherosclerosis. However, the contribution of MRTF-A to the development of atherosclerosis remains unclear. Macrophages are known to be important mediators of atherosclerosis. In this study, we found that MRTF-A was highly expressed in lesional macrophages in human carotid atherosclerotic plaque. To investigate the role of macrophagic MRTF-A in the pathogenesis of atherosclerosis, we generated ApoE null MRTF-A transgenic mice (ApoE−/−/MRTF-Atg/+), in which human MRTF-A was specifically overexpressed in monocytes/macrophages. We found that ApoE−/−/MRTF-Atg/+ aggravated atherosclerosis and accumulated prominent lesional macrophages in the aortic sinus. We also found that MRTF-A promoted proliferation of macrophages and mitigated apoptosis both in vitro and in vivo due to downregulation of the expression of cyclin-dependent kinase inhibitors. Taken together, our data indicated that MRTF-A contributes to the development of atherosclerosis by modulating functional properties of pro-atherogenic macrophages.
Verapamil-sensitive atrial tachycardia originating from the atrioventricular node vicinity (AVN-AT) can be eliminated with radiofrequency energy (RF) deliveries targeting either the entrance or exit ...of its reentry circuit. However, the outcome of these different approaches has not been clarified well. Thus, we compared the catheter ablation outcome targeting the entrance of reentry circuit, identified by the entrainment method (Ent-Group; 21 patients) with that targeting the earliest atrial activation site (EAAS) during AT (Exit-Group; 16 patients). There was no significant difference in the tachycardia cycle length (441.4 ± 87.4 vs. 392.8 ± 64.8 ms,
p
= 0.0704) or distance from the His bundle (HB) site to the EAAS (6.5 ± 2.0 vs. 7.6 ± 1.8 mm,
p
= 0.0822) between the Ent- and Exit-Groups. However, distance from the successful ablation site to the HB site in the Ent-Group was significantly longer than that in the Exit-Group (13.4 ± 3.1 vs. 7.6 ± 1.8 mm,
p
< 0.0001), resulting in more frequent transient atrioventricular block episodes in the Exit-Group than Ent-Group (31.3 vs. 0%,
p
< 0.01). Initial ATs (AT1s) were terminated in all patients in both Groups. However, ATs accompanied by shifting in the EAAS (AT2) were induced more frequently in the Exit-Group than Ent-Group (50.0 vs. 14.3%,
p
< 0.02) after eliminating AT1. RF deliveries to the EAAS eliminated all AT2s. The number of RF deliveries was greater in the Exit-Group than Ent-Group (6.9 ± 3.3 vs. 3.9 ± 1.6,
p
< 0.001). In conclusion, RF ablation targeting the entrance sites can avoid AVN injury and is superior in reducing the number of RF deliveries and occurrence of different ATs than targeting the exit sites in the AVN-AT.
Fractional flow reserve (FFR) has become an increasingly important index for decision making concerning coronary revascularization. It is commonly accepted that significant improvement in FFR ...following percutaneous coronary intervention (PCI) is associated with better symptomatic relief and a lower event rate. However, in lesions with insufficient FFR improvement, PCI may not improve prognosis. Leading to the observation that the clinical and angiographic characteristics associated with insufficient FFR improvement have not been fully explored. The purpose of this study was to investigate the factors associated with insufficient improvement in FFR. Using our own PCI database, established between January 2014 and December 2018, we identified 220 stable coronary artery lesions, which had been evaluated for both pre- and post-PCI FFR values. All 220 of these lesions were included in this study. The improvement in FFR (ΔFFR) was calculated in each lesion with the lowest quartile of ΔFFR being defined as the lowest ΔFFR group, and the other quartiles being defined as the intermediate-high ΔFFR group. The mean ΔFFR in the lowest and intermediate-high ΔFFR groups was 0.07 ± 0.02 and 0.21 ± 0.11, respectively. In multivariate logistic regression analysis, a short total stent length (10 mm increase: OR 0.67, 95% CI 0.47–0.96,
P
= 0.030), higher pre-PCI FFR (0.1 increase: OR 4.07, 95% CI 1.83–9.06,
P
= 0.001), in-stent restenosis (ISR) (OR 8.02, 95% CI 1.26–51.09,
P
= 0.028), myocardial infarction (MI) in the target vessel (OR 6.87, 95% CI 1.19–39.69,
P
= 0.031) and non-use of intravascular imaging (OR 0.35, 95% CI 0.12–0.99,
P
= 0.048) were significantly associated with the lowest ΔFFR group. The use of short stents, higher pre-PCI FFR values, ISR, MI in the target vessel, and non-use of intravascular imaging were significantly associated with insufficient FFR improvement. It was conversely suggested that full coverage and adequate dilatation of the lesions under an intravascular imaging guidance might contribute to an improvement in FFR.
Gangliosides are expressed in nervous systems and some neuroectoderm-derived tumors at high levels and play pivotal roles. However, mechanisms for the regulation of glycosyltransferase genes ...responsible for the ganglioside synthesis are not well understood. In this study, we analyzed DNA methylation patterns of promoter regions of
GD3 synthase
(
ST8SIA1
) as well as mRNA levels and ganglioside expression using human glioma cell lines. Among 5 cell lines examined, 4 lines showed changes in the expression levels of related genes after treatment with 5-aza-dC. LN319 showed up-regulation of St8sia1 and increased b-series gangliosides after 5-aza-dC treatment, and an astrocytoma cell line, AS showed high expression of
ST8SIA1
and b-series gangliosides persistently before and after 5-Aza-2’-deoxycytidine treatment. Using these 2 cell lines, DNA methylation patterns of the promoter regions of the gene were analyzed by bisulfite-sequencing. Consequently, 2 regions that were methylated before 5-Aza-2’-deoxycytidine treatment were demethylated in LN319 after the treatment, while those regions were persistently demethylated in AS. These 2 regions corresponded with sites defined as promoter regions by Luciferase assay. Taken together, it was suggested that
ST8SIA1
gene is regulated by DNA methylation at the promoter regions, leading to the regulation of tumor phenotypes.
The clinical benefits of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is still controversial. The purpose of this study is to assess the quantitative therapeutic ...benefits of successful PCI for CTO from the clinical data acquired by myocardial perfusion imaging (MPI). Consecutive 42 patients, who were successfully revascularized of CTO between August 2013 and March 2018, were examined. A stress MPI was performed before CTO PCI and at follow-up, and the changes in quantitative gated and perfusion single photon emission computed tomography parameters were examined. The follow-up interval was 18 ± 9 (median 14) months, during which 36 patients were maintained patency (patent CTO), while 6 were re-occluded (R/O CTO). The reduction in the % myocardial ischemia and the improvement in the ejection fraction were significantly higher in the patent CTO group than those in the R/O CTO group (67.5 ± 37.0% vs. − 56.4 ± 84.9%,
p
< 0.0001, 20.7 ± 49.8% vs. − 9.2 ± 20.6%,
p
= 0.0247, respectively). Interestingly, the improvements we observed were predominantly in the patients with LAD CTO rather than those with RCA or LCx CTO. Successful CTO PCI was able to reduce myocardial ischemia and improve the cardiac function when the patency after CTO PCI was maintained, with the most notable significance in the patients with LAD CTO.
Acute coronary syndrome (ACS) is associated with a high incidence of unstable plaques beyond the culprit lesion, leading to early recurrence of cardiovascular events. Coronary computed tomography ...angiography (CCTA) can be used to non-invasively observe plaques throughout the coronary arteries. To evaluate the impact of intensive low-density lipoprotein cholesterol (LDL-C)-lowering therapy on quantitative changes in coronary plaque, assessed using CCTA in a study population with ACS. Eighty-one consecutive patients with ACS who underwent CCTA at discharge and at 1-year follow-up from April 2018 to March 2020 were analyzed. The patients were divided into two groups: those who achieved LDL-C < 70 mg/dl and those who did not. Changes in plaque morphology within and between the two groups were compared using CCTA. A total of 198 vessels were analyzed. The calcified plaque volume was significantly increased in the LDL-C < 70 group (65.8 ± 80.1 mm3 to 73.6 ± 83.7 mm3, p = 0.007), while no significant change was observed in the LDL-C ≥ 70 group (106.9 ± 161.7 mm3 to 105.7 ± 137.5 mm3, p = 0.552). Percent change in low-attenuation plaque (LAP) volume in LDL < 70 group was significantly lower than in the LDL-C ≥ 70 group (17.2 ± 90.9% versus 84.4 ± 162.6%, p = 0.020). Receiver operating characteristic curve analysis demonstrated that the target LDL-C level for LAP volume regression was 64 mg/dl. In conclusion, noninvasive CCTA demonstrated that intensive LDL-C lowering in high-risk patients with ACS could potentially lead to plaque stabilization.
The efficacy of catheter ablation from the noncoronary aortic cusp (NCC) of verapamil-sensitive atrial tachycardia arising near the atrioventricular node (AVN-AT) has yet to be fully clarified.
We ...elucidated the determinant of an effective AVN-AT ablation from the NCC.
After identifying the earliest atrial activation site (EAAS) during tachycardia, the direction of the slow conduction zone (SCZ) of the reentry circuit was identified by demonstrating manifest entrainment in 26 patients with AVN-AT. Catheter ablation was initially performed from the NCC irrespective of the local activation time. If NCC ablation was ineffective, catheter ablation was performed targeting the SCZ entrance. Then the anatomical relationship between the SCZ and the successful ablation site was elucidated.
NCC catheter ablation terminated AVN-AT in 14 patients (NCC group) but not in 12 (non-NCC group). Catheter ablation targeting the SCZ entrance terminated all non-NCC group ATs. The local activation time at the NCC relative to the EAAS did not differ between the NCC and non-NCC groups (10.1 ± 6.5 ms vs 11.2 ± 4.8 ms; P = .6333). The direction of the SCZ was posterior to the EAAS in all NCC group patients; however, it was posterolateral (n = 5) and lateral (n = 7) to the EAAS in the non-NCC group, suggesting that the SCZ existed in the direction of the NCC in the NCC group but was away from the NCC in the non-NCC group.
A close proximity between the NCC and the SCZ of the reentry circuit, but not the local activation time at the NCC, determined the efficacy of NCC catheter ablation in AVN-ATs.
Fraction flow reserve (FFR) derived from computed tomography (FFRCT) has been proposed to be an effective gatekeeper for invasive angiographic referral. The purpose of the present study is to examine ...the real-world diagnostic performance of FFRCT and myocardial perfusion imaging as well as to assess the utility of FFRCT as a gatekeeper for invasive coronary angiography in patients suspected of having obstructive coronary artery disease. Total of 146 consecutive patients underwent both single-photon emission computed tomography (SPECT) and invasive FFR were evaluated. An FFRCT value 1 to 2 cm distal to a stenosis ≤0.80 was defined as positive for ischemia and a summed stress score ≥2 or transient ischemic dilatation ≥1.2 were positive for ischemia with the invasive FFR value of <0.80 serving as the gold standard. The patient-based sensitivity of FFRCT was significantly higher than SPECT (91 vs 52%, p <0.001) and exhibited similar positive predictive value (82 vs 82%, p = 0.91). These trends were observed even in patients with multivessel and left main trunk disease and those with severe coronary calcification. In conclusion, our data suggest that FFRCT has higher diagnostic performance characteristics than SPECT and details the superior FFRCT analysis in detecting patients with hemodynamically significant coronary artery disease. Our results support the clinical utility of FFRCT analysis as a gatekeeper for invasive coronary angiography in clinical practice.
We investigated the hemostatic effect and safety of a hemostatic peptide solution for the treatment of gastrointestinal bleeding requiring emergency endoscopy.
We retrospectively examined the patient ...backgrounds, hemostatic results, and procedural safety in patients who were treated with a hemostatic peptide solution for hemostasis during emergency endoscopies for gastrointestinal bleeding. All hemostatic procedures were performed by nonexpert physicians with less than 10 years of endoscopic experience. All of the cases were treated at a single institution over the months from January 2022 to January 2023.
Twenty-six consecutive patients (17 males and 9 females) with a median age of 74 (45-95) years were included. Their conditions requiring emergency endoscopy were melena in 8 patients, hematochezia in 2, hematemesis in 8, anemia in 6, and bleeding during esophagogastroduodenoscopy in 2. The sites of bleeding were the esophagus in 3 patients, the stomach in 17, the duodenum in 3, the small intestine in 2, and the colon in 1. Hemostasis was obtained with another hemostasis device used in conjunction with the hemostatic peptide solution in 13 cases and with the hemostatic peptide solution alone in 13 cases. The hemostasis success rate was 100%, with no complications. Rebleeding occurred within 1 week in 4 cases.
Hemostasis with the hemostatic peptide solution was safe and provided a temporary high hemostatic effect in emergency gastrointestinal endoscopy.
Background:The optimal site for measuring computed tomography (CT)-derived fractional flow reserve (FFRCT) to detect significant coronary artery disease (CAD) remains unknown. We investigated how ...diagnostic performance changes with FFRCTmeasurement site.Methods and Results:The diagnostic performance of FFRCT, measured 1–2 cm distal to the stenosis vs. a far-distal site, in detecting significant CAD with invasive fractional flow reserve ≤0.8 was evaluated in 254 diseased vessels from 146 patients with stable or suspected CAD diagnosed by coronary CT angiography. Receiver operating characteristic curve analysis revealed a significantly larger area under the curve for FFRCTmeasured 1–2 cm distal to the stenosis than at a far-distal site (0.829 vs. 0.791, respectively; P=0.0305). The rate of reclassification of positive FFRCTwas 19% for measurements made 1–2 cm distal to the stenosis, and diagnostic accuracy for FFRCT0.71–0.80 improved from 36% to 58% (P=0.0052). Vessel-based diagnostic accuracy of FFRCT1–2 cm distal to the stenosis and at a far-distal site was 75% and 65%, respectively (P<0.0001), with corresponding sensitivity of 87% and 94% (P=0.0039), specificity of 60% and 29% (P<0.0001), a positive predictive value of 73% and 62% (P=0.028), and a negative predictive value of 78% and 79% (P=0.958).Conclusions:Our data suggest measuring FFRCT1–2 cm distal to the stenosis has better diagnostic performance for detecting physiologically significant CAD.
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