Randomized comparison between 2-link cell design biolimus A9-eluting stent and 3-link cell design everolimus-eluting stent in patients with de novo true coronary bifurcation lesions: the BEGIN trial.

The appropriate stent platform for treating coronary bifurcation lesions (CBLs) remains controversial. Previous bench tests have demonstrated the superiority of a 2-link cell design to 3-link cell design for creating inter-strut dilation at the side branch ostium. This randomized multicenter prospective BEGIN trial compared the biodegradable polymer-based biolimus A9-eluting stent (2-link BES) with the durable polymer-based cobalt chromium everolimus-eluting stent (3-link EES) in 226 patients with de novo CBLs. Patients with true bifurcations, defined as > 50% stenosis in the main vessel and side branch (SB) and an SB diameter > 2.25 mm, were enrolled. Guide wire re-crossing to the distal cell (near the carina) in the jailed SB and final kissing inflation were recommended. The SB angiographic endpoint was < 50% stenosis diameter. Left-main CBLs (13.5% vs. 13.0%) and 2-stent technique (30.6% vs. 22.6%) rates were similar. The primary endpoints (minimum lumen diameter at the SB ostium measured at an independent core laboratory at the 8-month follow-up) were comparable (1.64 ± 0.50 mm vs. 1.63 ± 0.51 mm, p = 0.976). There was no significant difference in composite outcomes of cardiac death, myocardial infarction, or target vascular revascularization at 12 months (7.4% vs. 8.0%, p = 0.894). Two-link BES and 3-link EES showed similar 8-month angiographic and 1-year clinical outcomes for true CBLs.

Comparison of the effects of linagliptin and voglibose on endothelial function in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, pilot study (EFFORT).

Endothelial dysfunction contributes to poor cardiovascular prognosis in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). The effect of dipeptidyl peptidase-4 inhibitors on endothelial function remains controversial. We sought to compare the effects of linagliptin and voglibose on endothelial function, as assessed by reactive hyperemia-peripheral arterial tonometry (RH-PAT). Sixteen patients with newly diagnosed T2DM and CAD were randomized 1:1 to linagliptin (5 mg, once-daily) or voglibose (0.9 mg, thrice-daily). The RH-PAT and laboratory parameters, including 75 g oral glucose tolerance test, were measured at baseline and 3 months. Linagliptin increased serum levels of active glucagon-like peptide-1 and high-molecular-weight adiponectin. Age-, sex-, and baseline-adjusted changes in logarithmic RH-PAT index (LnRHI) after 3 months were significant between groups (linagliptin, 0.135 ± 0.097; voglibose, - 0.124 ± 0.091; P = 0.047). In the linagliptin group, change in LnRHI was positively correlated with change in high-density lipoprotein cholesterol and negatively correlated with changes in both urine albumin-to-creatinine ratio and high-sensitivity C-reactive protein. Furthermore, linagliptin treatment for 3 months reduced serum levels of both glucose and insulin at 2 h, relative to voglibose, in the age-, sex-, and baseline-adjusted model. Linagliptin improved endothelial function relative to voglibose, accompanied by amelioration of glycemic, renal, and cardiometabolic parameters, in patients with newly diagnosed T2DM and CAD.Trial registration Unique Trial Number, UMIN 000029169 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012442 ).

Prolonged Inflation Technique Using a Scoring Balloon for Severe Calcified Lesion.

Percutaneous coronary intervention for the treatment of a severe calcified lesion is still one of the most technically challenging areas of interventional cardiology. Calcified lesions are a cause of stent underexpansion, which significantly increases the subsequent risks of in-stent restenosis and thrombosis, even when drug-eluting stents are used. In this report, we describe the usefulness of prolonged inflations using a scoring balloon catheter (Scoreflex) for severe calcified lesions. Prolonged inflation using a scoring balloon enables an adequate dilation for treatment of a severe calcified plaque that was unresponsive to conventional technique with or without rotational atherectomy.

Black hole restenosis after drug-eluting stent implantation for in-stent restenosis: potential mechanism and optimal strategy.

In-stent restenosis (ISR) has long remained as the major limitation of coronary stenting. The use of drug-eluting stent (DES) reduces the risk of repeat revascularization without an increase of death and myocardial infarction, compared to the standard bare metal stents. DES has also demonstrated markedly to reduce ISR for complex lesions. However, ISR after DES implantation still occurs and optimal treatment for ISR after DES has not been established. Herein, we report 3 cases with black hole restenosis confirmed by intravascular ultrasound at the site of overlapped DES and discuss potential mechanism and optimal strategy for this phenomenon.

Early Phase Arterial Reaction Following Drug-Eluting and Bare-Metal Stent Implantation in Patients With ST-Segment Elevation Myocardial Infarction.

The early phase arterial reaction after implantation of second-generation drug-eluting stents (2nd DES) and baremetal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear.The MECHANISM pilot study is a multi-center prospective registry that enrolled 24 STEMI patients (from 11 centers) who had undergone implantation of everolimus-eluting (n = 6), biolimus A9-eluting (n = 6) or zotarolimus-eluting stents (n = 6), or BMS (n = 6). Scheduled optical coherence tomography (OCT) was performed 2 weeks after implantation, and images were independently analyzed at a core laboratory in a blinded fashion. Intra-stent thrombus was quantitatively analyzed in terms of the maximal area and the percentage of cross-sections with thrombus (the numbers of cross-section with thrombus × 100 divided by total number of cross-sections within the stented segment). More than 90% of struts were already covered 2 weeks after the index procedure, regardless of the stent type. There were no differences in stent diameter, minimal lumen diameter, minimal lumen area, neointimal thickness, or the frequencies of malapposed and uncovered struts among the 4 groups. The quantity of intra-stent thrombus also did not differ among the 4 groups.The results of this pilot study suggest that the 2-week vascular responses seem to be similar among 2nd DES and BMS in STEMI patients. Considering the possible advantage of 2nd DES in the prevention of restenosis, 2nd DES are a feasible option for the treatment of patients with STEMI.

Right versus left coronary artery involvement in patients with type A acute aortic dissection.

BACKGROUND: Type A acute aortic dissection (AAD) complicated by coronary malperfusion is a life-threatening disease. In the present study, we compared the clinical characteristics and prognostic impact of treatment strategies including surgical treatment and percutaneous coronary intervention (PCI) in type A AAD patients with RCA and LCA involvement. METHODS: This multicenter registry included 220 patients with type A AAD and either RCA or LCA involvement. Treatment strategies were left to treating physicians. The primary endpoint was in-hospital death. RESULTS: Of 220 patients, 115 (52.3%) and 105 (47.7%) had RCA and LCA involvement. Patients with LCA involvement were more1 likely to present with Killip class IV on admission than those with RCA involvement. Coronary angiography was performed in 52 of 220 (23.6%) patients, among whom 39 (75.0%) underwent subsequent PCI. During the hospitalization, 93 (42.3%) patients died. Patients with LCA involvement had an increased risk of in-hospital mortality compared to those with RCA involvement (54.3% vs. 31.3%, p < 0.001). In patients with RCA involvement, multivariable analysis identified Killip class IV and no surgical treatment as predictors of in-hospital death, while PCI and surgical treatment were indicated as factors associated with lower in-hospital mortality in patients with LCA involvement. CONCLUSIONS: The rates of RCA and LCA involvement were similar in type A AAD. Immediate PCI as a bridge to subsequent surgical treatment might improve survival in patients with type A AAD complicated by coronary malperfusion, especially in those with LCA involvement.

Diffuse in-stent restenosis of CYPHER® stent due to hypersensitivity reaction confirmed by pathohistological findings.

The use of drug-eluting stents (DES) reduces the risk of repeat revascularization without increase of death and myocardial infarction compared to standard bare metal stents. However, in-stent restenosis (ISR) after DES implantation still occurs. Here, we report a rare case with a diffuse ISR after CYPHER® stent implantation because of chronic inflammation and hypersensitivity reactions, confirmed by pathohistological findings.

Comparison of haemodialysis patients and non-haemodialysis patients with respect to clinical characteristics and 3-year clinical outcomes after sirolimus-eluting stent implantation: insights from the Japan multi-centre post-marketing surveillance registry.

AIMS: Long-term outcomes after sirolimus-eluting stent (SES) implantation in haemodialysis (HD) patients have remained controversial. We investigated the impact of HD on outcomes after SES implantation. METHODS AND RESULTS: We analysed the data on 2050 patients who underwent SES implantation in a multi-centre prospective registry in Japan. Three-year clinical outcomes were compared between the HD group (n = 106) and the non-haemodialysis (NH) group (n = 1944). At the 3-year clinical follow-up, the rates of unadjusted cardiac mortality (HD: 16.3 vs. NH: 2.3%) and target-lesion revascularization (TLR) (HD: 19.4 vs. NH: 6.6%) were significantly higher in the HD group than the NH group (P < 0.001). Although HD group had a numerically higher stent thrombosis rate, the difference in stent thrombosis between the two groups (HD: 2.0 vs. NH: 0.7%) did not reach statistical significance. Using Cox's proportional-hazard models with propensity score adjustment for baseline differences, the HD group had higher risks of TLR [HD: 16.3 vs. NH: 6.1%; hazard ratio, 2.83; 95% confidence interval (CI): 1.62-4.93, P = 0.0003] and cardiac death (HD: 12.3 vs. NH: 2.3%; hazard ratio, 5.51; 95% CI: 2.58-11.78, P < 0.0001). The consistent results of analyses, whether unadjusted or adjusted for other baseline clinical and procedural differences, identify HD as an independent risk factor for cardiac death and TLR. CONCLUSIONS: Percutaneous coronary intervention with SES in HD patients has a higher incidence of repeat revascularization and mortality compared with those in NH patients. Haemodialysis appears to be strongly associated with mortality and repeat revascularization even after SES implantation.

Ultrathin, Biodegradable-Polymer Sirolimus-Eluting Stent vs Thin, Durable-Polymer Everolimus-Eluting Stent.

BACKGROUND: Previous trials suggested the superiority of ultrathin- over thin-strut drug-eluting stents (DES) concerning target lesion failure (TLF) at 1 year after index percutaneous coronary intervention. OBJECTIVES: The aim of this randomized comparison study of ultrathin-strut and thin-strut DES (CASTLE [Randomized Comparison All-Comer Study of Ultrathin Strut and Thin Strut Drug-Eluting Stent]; jRCTs032180084) was to examine the impact of differences in strut thickness of DES on clinical outcomes when implanted with angiography and intravascular ultrasound or optical coherence tomographic guidance. METHODS: CASTLE was a multicenter, prospective, noninferiority study conducted at 65 institutions in Japan. Percutaneous coronary intervention patients were assigned (1:1) to an ultrathin, biodegradable-polymer sirolimus-eluting stent (BP-SES) or a thin, durable-polymer everolimus-eluting stent (DP-EES). The primary endpoint was TLF, defined as a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target lesion revascularization at 1-year follow-up. RESULTS: Between May 2019 and March 2020, 1,440 patients were randomly assigned to BP-SES (n = 722) or DP-EES (n = 718). TLF occurred in 6.0% and 5.7% of patients, respectively. Noninferiority (P = 0.040) was met because the upper limit (2.67%) of the 1-sided 95% CI between the groups was lower than the prespecified noninferiority margin (3.3%). No significant interactions were observed in the relative rates of TLF between prespecified subgroups. CONCLUSIONS: The BP-SES was noninferior to the DP-EES regarding 1-year TLF. This demonstrates that strut thickness differences among DES have little impact on clinical outcomes when implanted with intravascular imaging guidance.

Sirolimus-eluting stent versus balloon angioplasty for sirolimus-eluting stent restenosis: Insights from the j-Cypher Registry.

BACKGROUND: Optimal treatment strategies for restenosis of sirolimus-eluting stents (SES) have not been adequately addressed yet. METHODS AND RESULTS: During the 3-year follow-up of 12 824 patients enrolled in the j-Cypher registry, 1456 lesions in 1298 patients underwent target-lesion revascularization (TLR). Excluding 362 lesions undergoing TLR for stent thrombosis or TLR using treatment modalities other than SES or balloon angioplasty (BA), 1094 lesions with SES-associated restenosis in 990 patients treated with either SES (537 lesions) or BA (557 lesions) constituted the study population for the analysis of recurrent TLR and stent thrombosis after the first TLR. Excluding 24 patients with both SES- and BA-treated lesions, 966 patients constituted the analysis set for the mortality outcome. Cumulative incidence of recurrent TLR in the SES-treated restenosis lesions was significantly lower than that in the BA-treated restenosis lesions (23.8% versus 37.7% at 2 years after the first TLR; P<0.0001). Among 33 baseline variables evaluated, only hemodialysis was identified to be the independent risk factor for recurrent TLR by a multivariable logistic regression analysis. After adjusting for confounders, repeated SES implantation was associated with a strong treatment effect in preventing recurrent TLR over BA (odds ratio, 0.44; 95% confidence interval, 0.32 to 0.61; P<0.0001). The 2-year mortality and stent thrombosis rates between the SES- and the BA-treated groups were 10.4% versus 10.8% (P=0.4) and 0.6% versus 0.6%, respectively. CONCLUSIONS: Repeated implantation of SES for SES-associated restenosis is more effective in preventing recurrent TLR than treatment with BA, without evidence of safety concerns.

Comparison of pharmacokinetics of the limus-eluting stents in Japanese patients.

OBJECTIVES: The aim of this study was to compare the pharmacokinetics of the four limus-eluting stents used in Japanese patients. BACKGROUND: There are presently no reports comparing human pharmacokinetics among drug-eluting stents (DESs). METHODS: We retrospectively analyzed data from pharmacokinetic studies of patients implanted with an 18-mm DES: Cypher stent (sirolimus, n = 10), Endeavor stent (zotarolimus, n = 7), Xience V stent (everolimus, n = 6), and Nobori stent (biolimus A9, n = 10), in multicenter trials of Japan. Total drug doses of the Cypher stent, Endeavor stent, Xience V stent, and Nobori stent were 150, 180, 88, and 293 µg, respectively. Drug concentrations were measured in serial whole blood samples after implantation and the pharmacokinetics were analyzed. RESULTS: Mean peak drug levels were 0.86 ng mL(-1) for Cypher, 1.80 ng mL(-1) for Endeavor, 0.50 ng mL(-1) for Xience V, and 0.09 ng mL(-1) for Nobori. After adjustment for the loaded dose, mean peak drug levels of the Cypher and Xience V stents were similar (0.0057 ng mL(-1) µg(-1) each) while the Endeavor (0.0100 ng mL(-1) µg(-1)) was higher, and the Nobori (0.0003 ng mL(-1) µg(-1)) was lower, compared with the Cypher and Xience V stents. The other pharmacokinetic parameters of four DESs differed according to characteristics of the coated drug. The systemic exposure of biolimus A9 was much lower than that of the other DESs studied. CONCLUSIONS: In Japanese patients, systemic exposure was low, regardless of the type of limus drug eluted from the stents; but specific pharmacokinetic activities were varied according to the drug characteristics, concentration, and DES design.

Effect of pretreatment with pioglitazone on reperfusion injury in diabetic patients with acute myocardial infarction.

BACKGROUND: Pioglitazone (PIO) is a new class of anti-diabetic agent with an anti-inflammatory effect. In the experimental studies, pretreatment with PIO before ischemia/reperfusion reduced ischemia-reperfusion injury and myocardial infarct size. However, the clinical efficacy of this therapy in patients with acute myocardial infarction (AMI) remains unknown. METHODS AND RESULTS: Three hundred and nineteen diabetic patients with ST-segment elevation AMI, treated with bare metal stent within 24h from the onset of AMI were examined. Myocardial blush grade, ST-segment resolution, peak creatine kinase (CK) level, and left ventricular ejection fraction (LVEF) were compared between PIO group (pretreatment with PIO [+]; n=26) and non-PIO group (pretreatment with PIO [-]; n=293). The PIO group showed a significantly higher incidence of blush score ≥ 2 and complete ST-segment resolution (blush score ≥ 2; 38% vs. 71%, P=0.04, ST-segment resolution; 44% vs. 71%, P=0.04). Besides, slow flow/no-reflow phenomenon and reperfusion arrhythmia did not occur in this group. Better improvement of LVEF and lower peak CK level was observed in this group, although these were not statistically significant (LVEF 48% vs. 41%, P=0.10, peak CK level 2,041 vs. 3,207, P=0.06). CONCLUSIONS: Pretreatment with PIO in diabetic patients with AMI resulted in better myocardial perfusion with less reperfusion injury.

Efficacy of paclitaxel-eluting stent in patients with impaired glucose tolerance--comparison with sirolimus-eluting stent.

BACKGROUND: Experimental and clinical studies have shown that paclitaxel-eluting stent (PES) attenuates the effect of diabetes on re-stenosis after percutaneous coronary intervention. Although impaired glucose tolerance (IGT) is a pre-diabetic phase characterized as post-prandial hyperglycemia and hyperinsulinemia, the efficacy of PES in these pre-diabetic patients remains unknown. The purpose of the present study was therefore to compare the efficacy of PES in IGT patients with that of sirolimus-eluting stent (SES). METHODS AND RESULTS: A total of 370 IGT patients with coronary artery disease were examined (SES, n=229; PES, n=141). The incidence of major adverse cardiovascular events (MACE; all-cause death, non-fatal myocardial infarction or repeat revascularization) was compared between the 2 groups. The PES group had lower body mass index, total cholesterol and low-density lipoprotein cholesterol levels and higher prevalence of previous myocardial infarction than the SES group. The incidence of repeat revascularization in the PES group was similar to that in the SES group (22% vs. 19%, P=0.71). The incidence of hard cardiac events such as all-cause death and non-fatal myocardial infarction were also similar between the 2 groups. Finally, there were no significant differences in MACE between the SES and PES groups (23% vs. 21%, P=0.76). CONCLUSIONS: In patients with IGT, the efficacy of PES was similar to that of SES, and any advantage of PES over SES was not observed in these pre-diabetic patients.

A rare connection by newly formed conduit vessels between the left internal mammalian artery and radial artery bypass grafts after failure of grafts.

Neovascularization such as formation of collateral vessels following total occlusion of native coronary artery is common in coronary artery disease. This is a case report of a very rare connection by newly formed conduit vessels between the left internal mammalian artery and the radial artery establishing bypass, which occurred after failure of bypass grafts.

Plasma microRNA 499 as a biomarker of acute myocardial infarction.

BACKGROUND: MicroRNAs (miRNAs) are endogenous small RNAs 21-25 nucleotides in length. Recently, we reported that miRNA 208 (miR-208) is produced exclusively in the rat myocardium and that plasma miR-208 is a biomarker of myocardial injury in rats. In the present study, we assessed the hypothesis that plasma concentrations of myocardial-specific miRNAs can be used to diagnose myocardial injury in humans. METHODS: We used array analysis of miRNA production in various human tissues to identify heart-specific miRNAs. We assessed the plasma concentrations of miR-499 in 14 individuals with acute coronary syndromes, 15 individuals with congestive heart failure, and 10 individuals without cardiovascular diseases. Plasma miR-499 concentrations were measured with a real-time reverse-transcription PCR method that used an artificial small RNA as an internal calibrator. RESULTS: The miRNA array analysis of various human tissues indicated that miR-499 was produced almost exclusively in the heart. Plasma miR-499 concentrations were measurably increased in all individuals with acute myocardial infarction but were below the limit of detection for all individuals in the other patient groups. CONCLUSIONS: The plasma concentration of miR-499 may be a useful biomarker of myocardial infarction in humans.

Post-load hyperglycemia as an important predictor of long-term adverse cardiac events after acute myocardial infarction: a scientific study.

BACKGROUND: Diabetes mellitus (DM) and impaired glucose tolerance (IGT) are risk factors for acute myocardial infarction (AMI). However, it is unknown whether hyperglycemic state is associated with increased major adverse cardiovascular events (MACE) after AMI. In this study, we evaluated the relationship between glucometabolic status and MACE in patients after AMI, and determined the critical level of 2 h post-load plasma glucose that may be used to predict MACE. METHODS: AMI patients (n = 422) were divided into 4 groups as follows: normal glucose tolerance (NGT) group, IGT group, newly diagnosed DM (NDM) group, and previously known DM (PDM) group. MACE of the 4 groups were compared for 2 years from AMI onset. RESULTS: The NDM group had a significantly higher event rate than the IGT and NGT groups and had a similar event rate curve to PDM group. The logistic models analyses revealed that 2 h post-load plasma glucose values of ≥160 mg/dL was the only independent predictor of long-term MACE after AMI (p = 0.028, OR: 1.85, 95% CI: 1.07-3.21). The 2-year cardiac event rate of patients with a 2 h post-load hyperglycemia of ≥160 mg/dL was significantly higher than that of patients with 2 h post-load glucose of <160 mg/dL (32.2% vs. 19.8%, p < 0.05) and was similar to that of PDM group (37.4%, p = 0.513). CONCLUSIONS: NDM increases the risk of MACE after AMI as does PDM. Particularly, post-AMI patients with a 2 h post-load hyperglycemia ≥160 mg/dL may need adjunctive therapy after AMI.

A 3-year clinical outcome after percutaneous coronary intervention using sirolimus-eluting stent and off-pump coronary artery bypass grafting for the treatment of diabetic patients with multivessel disease.

BACKGROUND: There are few data to compare the long-term efficacy of sirolimus-eluting stent (SES) and off-pump coronary artery bypass grafting (OPCAB) for diabetic patients with multivessel disease (MVD). METHODS AND RESULTS: In a single-center non-randomized registry, 208 diabetic patients with MVD were examined (SES group: n=92, OPCAB group: n=116). The occurrence of major adverse cardiac and cerebrovascular events (MACCE, defined as all-cause death, non-fatal myocardial infarction, cerebrovascular event, and repeat revascularization) was compared between the 2 groups. Fasting blood glucose level, type of diabetic treatment and the prevalence of diabetic major vascular complications were similar between groups. The SES group had a significantly higher prevalence of 2-vessel disease and a significantly lower prevalence of 3-vessel disease compared with the OPCAB group. During the follow-up period (mean: 42+/-8 months), the rate of revascularization was significantly higher in the SES group than the OPCAB group (21% vs 6.9%, P=0.003). On the other hand, there was a significant higher occurrence of cerebrovascular events in the OPCAB group. Finally, the cumulative MACCE was similar between the 2 groups (27% vs 23%, P=0.492). CONCLUSIONS: At the 3-year clinical follow-up, the prevalence of MACCE in diabetic patients with MVD was comparable between the SES and the OPCAB groups.

Coronary vasospasm secondary to allergic reaction following food ingestion: a case of type I variant Kounis syndrome.

Coronary vasospasm can be induced by allergic reactions with some chemical mediators, and the angina and myocardial infarction secondary to allergy-induced coronary vasospasm are referred to as "Kounis syndrome." Only two cases of Kounis syndrome following food ingestion have been reported. However, they had pre-existing atheromatous coronary artery disease, and no provocation test to induce coronary vasospasm was done. We describe here another probable case of allergic vasospasm after food intake. To the best of our knowledge, this is the first documented report of a patient with food-induced allergic vasospasm subsequent to the provocation test with ergometrine maleate.