Role of Dual-Acquisition Noninvasive Cardiac CT Imaging for the Detection of Vasospastic Angina.

BACKGROUND: Vasospastic angina (VSA) is characterized by chest pain at rest with transient ischemic electrocardiographic changes in the ST segment, and a prompt response to nitrates. Vasospastic angina is among the most frequent of the coronary artery diseases in Asia, and coronary computed tomography angiography (CCTA) may become available as a non-invasive diagnosis method. METHODS: We prospectively enrolled 100 patients with suspected vasospastic angina at two centers from 2018 to 2020. All patients underwent baseline CCTA without a vasodilator in the early morning followed by catheterized coronary angiography and spasm testing. CCTA with intravenous infusion of nitrate (IV) was repeated within 2 weeks of baseline CCTA. Vasospastic angina as detected by CCTA was defined as significant stenosis (≥50%) with negative remodeling without definite plaques or diffuse small diameter (<2 mm) of a major coronary artery with a beaded appearance on baseline CT that completely dilated on IV nitrate CT. We analyzed diagnostic performance of dual-acquisition CCTA for the detection of vasospastic angina. RESULTS: The patients were categorized into three groups according to their provocation test result (negative, n = 36; probable positive, n = 18; positive, n = 31). The diagnostic accuracy in terms of CCTA per patient had a sensitivity of 55% (95% CI, 40-69), specificity of 89% (95% CI, 74-97), positive predictive value (PPV) of 87% (95% CI, 72-95), and negative predictive value (NPV) of 59% (95% CI, 51-67). CONCLUSIONS: Dual-acquisition CCTA can support the non-invasive detection of vasospastic angina with relatively good specificity and PPV. CCTA was helpful for non-invasive screening of variant angina.

Oral N-acetylcysteine for prophylaxis of contrast-induced nephropathy in patients following coronary angioplasty: A meta-analysis.

It is acknowledged that contrast-induced nephropathy (CIN) is a common cause of acute renal insufficiency after cardiac catheterization and affects mortality and morbidity. To date, it is unknown whether oral N-acetylcysteine (NAC) is able to prevent contrast-induced nephropathy (CIN) in patients undergoing coronary angioplasty. A meta-analysis of randomized controlled trials was performed to assess the effects of NAC in the prevention of CIN in patients following coronary angioplasty. A total of 19 studies published prior to January 2015 that investigated the efficacy of oral NAC for the prevention of CIN were collected from Medline, Cochrane and Embase databases and conference proceedings from cardiology and nephrology meetings. The primary point of investigation was CIN, and the secondary points were renal failure requiring dialysis, mortality and length of hospitalization. The meta-analysis was performed using fixed- or random-effect models according to heterogeneity. Up to January 2015, 19 randomized placebo-controlled clinical trials met the inclusion criteria for the meta-analysis, including 4,514 patients. The pooled data showed that oral NAC did not reduce the CIN incidence [relative risk 0.84, 95% confidence interval (CI) 0.65-1.10; P=0.20], without heterogeneity among trials (I2=29%). Thus, the present meta-analysis suggests that oral NAC therapy is not effective as an alternative treatment to prevent CIN in patients following angioplasty. Further high quality randomized clinical controlled trials are required to confirm the usage and availability of this treatment.

Down regulation of Jag-1 in VSMCs contributes to impaired angiogenesis under high glucose condition: Experimental study using aortic rings of rats.

The major cause of diabetes-related mortality is the complications involving aberrant angiogenesis. To understand the underlying mechanisms of such altered-angiogenesis in diabetes, examining the interaction between endothelial cells (ECs) and neighboring smooth muscle cells (VSMCs) rather than mainly focusing on EC might provide us useful information. Thus, in the present study, we examined the effect of high glucose on the expression of Jag1, one of the key trans-activating ligands of Notch receptors known to be involved in EC-SMC interaction, as well as angiogenic process, in vascular smooth muscle cells (VSMCs) to elucidate possible role of EC-VSMC interaction in diabetes-related angiopathy. Our data indicate that high glucose condition decreases the expression of Jag1 in VSMCs possibly by increasing Jag1-targeting micro RNAs (miRNAs) such as miR-21, and exogenous Jag1-simulating peptides increase proliferation and migration of ECs under high glucose condition in vitro. Ex vivo study using aortic rings from normal and streptozotocin (STZ)-treated diabetic mouse demonstrated that exogenous Jag1-simulating peptides increases EC sprouting of aortic rings from diabetic mouse under high glucose condition. Our data suggest that EC-VSMC interaction is altered under high glucose condition and restoring EC-VSMC interaction can be a feasible therapeutic target for treating diabetes-related angiopathy.

Experience with a novel retrograde wiring technique for coronary chronic total occlusion.

OBJECTIVES: We report our evaluation of a novel retrograde wiring technique known as the Rendezvous method. BACKGROUND: Different strategies of retrograde approaches can be used to improve the success rate of recanalization of coronary chronic total occlusion (CTO). We previously introduced the Rendezvous technique as an alternative final step for a retrograde CTO procedure. METHODS: From July 2007 to May 2010, 20 CTO patients were treated in two medical centers using the Rendezvous method, which is an alternative to the conventional final externalization method to complete the retrograde CTO procedure. It involves crossing of the guidewire through the CTO segment using 2 microcatheters. RESULTS: The majority of the CTO sites were in the proximal right coronary artery (50.0%). Most of the lesions had mild to moderate calcification (95.0%) and revealed an abrupt stump with a side branch at the occlusion site. The lesion length of the occlusion was relatively long (median 27.6 mm; range of 7.1-87.3 mm). No adverse cardiac events occurred during hospitalization. CONCLUSION: The Rendezvous method used during the retrograde approach can be performed as an alternative to the conventional "externalization method" after the guidewire and microcatheter have crossed the occluded proximal segment into the opposite guiding catheter.

Effect of different anticoagulants on multiple electrode platelet aggregometry after clopidogrel and aspirin administration in patients undergoing coronary stent implantation: a comparison between citrate and hirudin.

Outcomes of platelet function tests are highly dependent on the type of blood anticoagulant used. The primary objective of this study was to clinically evaluate the platelet function after dual antiplatelet therapy using two different types of anticoagulant (citrate and hirudin). We compared data obtained from multiple electrode platelet aggregometry (MEA) with reference to light transmission aggregometry (LTA) and VerifyNow (VN) assays. Blood samples were obtained from 119 patients on dual antiplatelet therapy at the time of PCI (PCI) and the following morning (post-PCI). The platelet function tests were performed using two anticoagulated (citrate or hirudin) blood types for MEA as well as citrated blood for LTA and VerifyNow assays. ADP-induced MEA values at PCI for citrated and hirudinated anticoagulants were 36.5 ± 14.3 AUC and 41.4 ± 18.2 AUC (p = 0.021) and post-PCI values were 28.2 ± 11.9 AUC and 28.3 ± 12.8 AUC (p = 0.95). Additionally, AA-induced MEA values at PCI by citrated and hirudinated blood was 13.4 ± 7.3 AUC and 17.6 ± 13.4 AUC (p < 0.01). Post-PCI AA-induced MEA values were 12.0 ± 6.7 AUC and 13.5 ± 8.5 AUC (p = 0.12), respectively. Significant correlations were observed between the two anticoagulants used for MEA and LTA or VN values under ADP-induced platelet stimulation. Citrate tubes are clinically adequate for MEA assays and provide a more economical alternative to hirudin for early and/or delayed phases after clopidogrel-loading doses.

Mesenchymal stem cells overexpressing GCP-2 improve heart function through enhanced angiogenic properties in a myocardial infarction model.

AIMS: In this study, our aim was to evaluate the angio-vasculogenic properties of human adipose tissue-derived mesenchymal stem cells overexpressing the granulocyte chemotactic protein (GCP)-2 (hASCs/GCP-2) and to determine possible therapeutic effects in an experimental ischaemic heart model. METHODS AND RESULTS: Quantitative real-time (qRT)-PCR results revealed that hASCs/GCP-2 expressed significantly higher levels of pro-angiogenic genes, including vascular endothelial growth factor (VEGF)-A, hepatocyte growth factor (HGF), and interleukin (IL)-8, when compared with control-vector transduced hASCs or human umbilical vascular endothelial cells (HUVECs). In addition, the anti-apoptotic insulin-like growth factor (IGF)-1 and Akt-1 were also highly up-regulated in the hASCs/GCP-2 cells. In vitro cell migration and proliferation assays showed that hASCs/GCP-2-derived conditioned media (CM) significantly accelerated the migration and proliferation of fibroblast cells. Examination of in vitro endothelial differentiation showed that hASCs/GCP-2 cells spontaneously formed vascular-like structures and highly expressed endothelial-specific genes and proteins. In vivo study results of our mouse myocardial infarction (MI) model revealed that hASCs/GCP-2 implantation improved the cardiac function and reduced the infarct size. Finally, transplanted hASCs/GCP-2 cells unexpectedly differentiated into endothelial cells and the engraftment rate was significantly higher than control groups. CONCLUSION: We suggest that overexpression of GCP-2 in stem cells has the potential to enhance their angiogenic and survival properties.

Impact of platelet function test on platelet responsiveness and clinical outcome after coronary stent implantation: platelet responsiveness and clinical outcome.

BACKGROUND AND OBJECTIVES: The aim of this study was to confirm the predictive cut-off values for P2Y12 reaction units (PRU) and aspirin reaction units (ARU) and to evaluate the clinical impact of VerifyNow® assays. SUBJECTS AND METHODS: From November 2007 to October 2009, 186 eligible patients were prospectively recruited. Post-treatment platelet reactivity was measured by VerifyNow® assays within 12 to 24 hours after intervention, followed by standard dual maintenance dose therapy for 1 year. All patients had scheduled clinical follow-ups at 1, 3, 6, and 12 months. RESULTS: The rate of low responders to clopidogrel, aspirin, and both drugs were 41.4%, 10.2%, and 3.8%, respectively. The predictive factors for low responsiveness to clopidogrel (PRU ≥240) were female sex, age, and non-use of cilostazol medication in our univariate analysis and age ≥65 years and non-use cilostazol in the multivariate analysis. The predictors of low responsiveness to aspirin (ARU ≥550) were male sex and age in both univariate and multivariate analyses. There was no significant difference in the clinical event rate with a cut-off value of PRU ≥240 or ARU ≥550 for 30 days and 1-year (p>0.05). CONCLUSION: Hyporesponsiveness to antiplatelet agents (namely aspirin and clopidogrel) was identified in about half of the patients. The cut-off point of PRU ≥240 or ARU ≥550 did not confer predictive value for 30-day or 1-year clinical event rates in patients who had undergone coronary intervention with drug-eluting stents.

Loading effect of 200 mg cilostazol on platelet inhibition in patients undergoing percutaneous coronary intervention.

To date, most studies conducted on cilostazol have examined its effects as an agent of maintenance-dose therapy, but its loading effects on platelet inhibition have never been reported. This study aimed to determine the loading effects of 200 mg cilostazol in addition to aspirin and clopidogrel on platelet inhibition in patients undergoing percutaneous coronary intervention.Sixty consecutive patients undergoing coronary intervention were enrolled and assigned to receive 300 mg of aspirin and clopidogrel with or without 200 mg of cilostazol. All loading doses were given at least 3 hours before percutaneous coronary intervention and followed by dual or triple maintenance-dose therapy. Platelet function tests were performed just before and at 24 hours and 30 days after percutaneous coronary intervention by light transmittance aggregometry and VerifyNow® P2Y12 assay.There were no significant differences in baseline or angiographic characteristics between the 2 groups. The results of platelet function tests revealed that the adjunctive loading dose of 200 mg of cilostazol induced more potent platelet inhibition compared to a dual regimen at each time point. Cilostazol reduced the incidence of high post-treatment platelet reactivity (HPPR).Adjunctive 200 mg cilostazol can improve platelet responsiveness to clopidogrel in the pre- and postprocedural phases, reducing the prevalence of HPPR.

Determination of the prevalence of aspirin and clopidogrel resistances in patients with coronary artery disease by using various platelet-function tests.

BACKGROUND: Dual therapy with aspirin and clopidogrel has emerged as the gold standard therapy for patients treated with drug-eluting stents (DES). However, there is variability in patients' responses to this antiplatelet therapy, and some patients continue to show ischemic recurrences after therapy. The purpose of the study was to compare the simultaneously obtained results of various platelet-function tests for assessing the prevalence of antiplatelet resistance in coronary artery disease patients undergoing DES therapy. METHODS: A total of 66 patients were administered a loading dose of aspirin, clopidogrel, and cilostazol at least 12 hr before stenting. The results of VerifyNow (Accumetrics, USA), multiplate analyzer (Dynabyte Medical, Germany), and vasodilator-stimulated phosphoprotein/P2Y12 (Biocytex, France) assays were compared with those of light transmission aggregometry (LTA) analysis. RESULTS: The P2Y12 reaction units and P2Y12% inhibition values obtained using the VerifyNow assay showed strong correlation (r) with the results of the LTA analysis. All tests results showed low concordance in defining the antiplatelet resistance in patients, and the degrees of agreement were as follows: 0 for aspirin reaction units; 0.25, P2Y12% inhibition; 0, aspirin-sensitive patients' identification test; 0.21, ADPtest; and 0.14, platelet reactivity index, expressed as the κ statistics. The prevalence of aspirin and clopidogrel resistances in patients resulted in remarkable variations, from 0% to 22.7% and from 9.1% to 48.5%, respectively. CONCLUSIONS: The clinical usefulness of the different assays for the correct classification of patients in terms of antiplatelet resistance remains unclear. Further studies are required to determine the best method for correlating the occurrences of adverse ischemic events.

High Plasma Levels of the B-type Natriuretic Peptide in Patients Without Heart Failure: Is There Clinical Significance?

We report a case of a 19-year-old female with an elevated plasma B-type natriuretic peptide (BNP) level, but without evidence of heart failure (HF). She presented with non-specific chest pain and a high level of the B-type natriuretic peptide, despite having unremarkable findings on physical examination, laboratory analysis, electrocardiogram, echocardiogram, chest X-ray, chest computed tomography, whole body scan, and coronary angiography. We attribute this finding to a genetic variation in the synthesis and cleavage of the natriuretic peptides.

A new retrograde wiring technique for chronic total occlusion.

To improve the success rate of percutaneous coronary intervention for coronary chronic total occlusion (CTO), different strategies of retrograde approach were introduced in recent years. The aim of this report is to describe a new retrograde wiring technique for CTO, the "Bridge or Rendezvous method." This new technique saves time, reduces cost, as well as reduces procedure-related complications.

Improvement of cardiac function and remodeling by transplanting adipose tissue-derived stromal cells into a mouse model of acute myocardial infarction.

BACKGROUND: We investigated the effect of adipose tissue-derived stromal cells (ADSC) therapy on cardiac contractility and remodeling in the C57BL/6 mouse model of acute myocardial infarction (AMI). METHODS: 30 adult male C57BL/6 mice were randomized into 2 groups, namely, AMI+media (control, n=15) and AMI+ADSC (n=15). AMI was produced by left anterior descending coronary artery ligation. After AMI induction, 1 x 10(6) ADSC or media were intramyocardially injected and the results compared. Echocardiographic and histological analyses of surviving mice (n=20) were conducted. Echocardiography was performed before cell implantation and 2 weeks after transplantation. RESULTS: LVEF and FS improved in the ADSC group compared to the control (P<0.01). LVEDD in the ADSC group decreased slightly from 4.65+/-0.63 mm to 4.14+/-0.53 mm compared to the control, but there was no statistical difference (P=0.072). LVESD decreased significantly in the ADSC group (P<0.05). A significant difference in scar formation and infarct size was observed between the ADSC and control group 2 weeks after AMI (P<0.05). ADSC were observed to migrate into injured sites and integrate into scar areas and increased vascular density in the infarct site compared to control group (P<0.05). Additionally, some transplanted ADSC expressed the endothelial marker. CONCLUSIONS: Echocardiography and histological analysis revealed that improvement in cardiac function and ventricular remodeling was better in the ADSC group than in the control. This suggests that ADSC is a good candidate for cell therapy in cardiovascular disease.

Initial experience of retrograde wire approach in coronary chronic total occlusion intervention.

BACKGROUND AND OBJECTIVES: Retrograde wire approach has been emerged as a useful tool to enhance success rate in coronary chronic total occlusion (CTO) intervention. Therefore, we tried to report the initial experience of retrograde approach and its clinical implication on CTO intervention. SUBJECTS AND METHODS: From February 2007 to July 2008, retrograde approaches were performed in 28 patients with 31 CTO lesions out of 61patients. A hydrophilic coated guidewire was inserted by using microcatheter or over-the-wire (OTW) balloon through the collateral channel (septal or epicardial artery) via several strategies. RESULTS: Mean age of patients was 63.4+/-11.6 years. Male and female were 20 and 8 patients, respectively. The target artery with CTO lesions included the right coronary artery (45.2%), the left anterior descending artery (51.6%), and the left circumflex artery (3.2%). The mean length of CTO lesion was 18.4+/-16.4 mm. Overall technical success rate was 64.5%. The success rate of primary attempt was 78.9%, while the success rate of immediate and secondary attempt was 41.7%. Collateral channel dissections were observed in 3 patients and no patients among these patients developed cardiac tamponade. One patient had a silent non-Q wave myocardial infarction (MI) after the procedure. One failed patient died suddenly 3 days after the procedure. After percutaneous coronary intervention (PCI) procedure, no case was performed target vessel revascularization (TVR), urgent coronary artery bypass graft (CABG), and urgent PCI. CONCLUSION: Retrograde approach is an evolving technique to improve the success rate of CTO intervention. After the learning curve period, this technique could be the useful tool to enhance success rate in CTO intervention.