Impact of the Antithrombotic Effects of Prasugrel on Mid-Term Vascular Healing in Acute Coronary Syndrome vs. Stable Coronary Artery Disease.

BACKGROUND: The impact of antiplatelet drug effects on mid-term local arterial responses following percutaneous coronary intervention (PCI) remains uncertain. We evaluated the impact of the platelet reactivity of prasugrel on mid-term vascular healing between acute coronary syndrome (ACS) and stable coronary artery disease (CAD).Methods and Results:We conducted a prospective, 12-center study in 125 patients with ACS and 126 patients with stable CAD who underwent PCI with an everolimus-eluting stent (EES) and received dual antiplatelet therapy (DAPT) with prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed immediately after PCI and at the 9-month follow-up to assess the association of P2Y12reaction units (PRU) with the frequency of malapposed or uncovered struts and intrastent thrombi (IST). The incidence of abnormal mid-term OCT findings did not different between the ACS and CAD arms, regardless of clinical presentation, except that uncovered struts were more frequent in the ACS than CAD arm. PRU at PCI was significantly associated with the frequency of IST at follow-up, but not with uncovered and malapposed struts. PRU at PCI was the only independent predictor of IST detected at follow-up (odds ratio 1.009). CONCLUSIONS: In patients undergoing EES implantation and receiving prasugrel, achieving an adequate antiplatelet effect at the time of stent implantation may regulate thrombus formation throughout the follow-up period.

Impact of dual antiplatelet therapy with adjusted-dose prasugrel on mid-term vascular response in patients undergoing elective percutaneous coronary intervention with everolimus-eluting stents.

The impact of dual antiplatelet therapy (DAPT) with adjusted-dose (3.75 mg/day) prasugrel for Japanese patients has not been fully investigated in terms of local arterial healing following the elective percutaneous coronary intervention (PCI). The ROUTE-01 elective study was a prospective, 12-center and single-arm registry that enrolled 123 patients who underwent elective PCI with everolimus-eluting stents (EESs) under DAPT with a combination of adjusted-dose prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed at the index PCI and 9-month follow-up to assess the relationship between in-stent thorombus (IST) and residual platelet reactivity measuring platelet reactivity unit (PRU). The patients were classified as extensive, intermediate, and poor metabolizers by cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms. The prevalence of IST was 9.0% by 9-month OCT, with no difference amongst the three groups (p = 0.886). The incidences of malapposed and uncovered struts were not different among the groups. PRU was not statistically different among the groups. In multivariate logistic regression analysis, the independent predictor for IST on 9-month OCT was irregular protrusion (odds ratio = 8.952, p = 0.037) on post-PCI OCT, not CYP2C19 loss-of-function polymorphisms. An adequate anti-thrombotic effect with an acceptable incidence of IST was observed irrespective of CYP2C19 loss-of-function polymorphisms. Our data suggests that adjusted-dose prasugrel and aspirin is a feasible treatment option in Japanese patients treated with EESs in elective PCI.

Vascular response to biolimus A-9 eluting stent in patients with shorter and prolonged dual antiplatelet therapy: optical coherence tomography sub-study of the NIPPON trial.

Dual antiplatelet therapy (DAPT) with thienopyridine and aspirin is the standard care for the prevention of stent thrombosis. However, the optimal duration and effect of the duration of DAPT on intra-stent thrombus (IS-Th) formation are unknown. The NIPPON study (Nobori Dual Antiplatelet Therapy as Appropriate Duration) was an open label, randomized multicenter, assessor-blinded, trial designed to demonstrate the non-inferiority of shorter (6-month) DAPT to prolonged (18-month) DAPT, after biolimus A9 eluting stent implantation in 3773 patients at 130 sites in Japan. Among them, 101 patients were randomly allocated for an optical coherence tomography (OCT) sub-study to assess the difference of local IS-Th formation between the two groups. In addition to standard OCT parameters, the number of IS-Th formed was counted in each target stent at 8 months. Baseline patient characteristics were not different between the 6- and 18-month groups. IS-Th was detected in 9.8% of the cases and the presence of IS-Th was not significantly different between the two groups (10.9% in 6-month vs. 9.1% in 12-month, P = 0.76). Furthermore, the number of IS-Th formed was not significantly different between the two groups. This OCT sub-study was in line with the main NIPPON study which demonstrated the non-inferiority of 6-month DAPT to 18-month DAPT. Shorter DAPT duration did not promote progressive IS-Th formation at the mid-term time point.

Fat embolism syndrome: A severe case diagnosed early using dual-energy CT and saved with VA-ECMO and inhaled nitric oxide.

Diagnosing FES is difficult and time-consuming, and identify FES as an etiology of right ventricular volume overload for early diagnosis. Because FES is a reversible condition, even severe cases can bse treated if the patient survives the acute phase.

A case of cough syncope diagnosed by the Valsalva maneuver and cough induction test under invasive arterial pressure measurement.

Following the loss of consciousness during the Valsalva maneuver and cough induction test, real-time arterial pressure measurement could clarify the significant blood pressure decrease in a patient with cough syncope.

Qualitative and quantitative assessment of stent restenosis by optical coherence tomography: comparison between drug-eluting and bare-metal stents.

BACKGROUND: We hypothesized that the tissue components of in-stent restenosis (ISR) might differ between drug-eluting stents (DES) and bare-metal stents (BMS) and that these differences could be distinguished by qualitative and quantitative optical coherence tomography (OCT) analyses. METHODS AND RESULTS: One-hundred and twenty-two initial ISR lesions (sirolimus-eluting stents: n=28; paclitaxel-eluting stents: n=51; BMS: n=43) were evaluated with OCT. Based on their OCT appearance, the lesions were classified as homogeneous, layered or heterogeneous. The optical properties of backscatter, attenuation and signal intensity of the neointimal tissue (NIT) were quantified. To evaluate the vascular response after balloon angioplasty (BA), the rate of reduction of the NIT area (NITA) was calculated (NITA before - after BA/NITA before BA at the minimum lumen cross-sectional area). Among the morphologic OCT patterns, the layered type was predominant with DES, whereas lesions were homogeneous with BMS (P<0.001). Backscatter and signal intensity were significantly higher with BMS (P<0.05 and P<0.001 respectively). The NITA reduction rate was significantly greater in the layered and heterogeneous groups than in the homogeneous group (P<0.01). CONCLUSIONS: The morphologic OCT patterns of the NIT in ISR differed significantly between DES and BMS, probably reflecting pathologic differences. Layered and heterogeneous tissues might respond better than homogeneous tissue to simple balloon dilatation, suggesting a possible direction for OCT-based ISR treatment strategies.

Pacemaker implantation for persistent sinus node dysfunction in a patient with COVID-19.

A 46-year-old woman was admitted with coronavirus disease-2019 infection. Symptomatic sinus bradycardia occurred, followed by congestive heart failure. Therapeutics such as isoproterenol, theophylline, and cilostazol could not safely improve her symptoms. She underwent pacemaker implantation 53 days after admission. Atrial pacing remained was at 60% after 6 months.

Less frequent post-thrombotic syndrome after successful catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis.

Post-thrombotic syndrome (PTS) occurs in 20-50% of patients with proximal deep vein thrombosis (DVT). In this study, we aimed to identify potential markers of thrombolysis success at the early stage and to clarify the relationship between early thrombolysis success and subsequent PTS development in patients with acute DVT in the iliac vein. Fifty-two consecutive patients with acute iliofemoral DVT who were treated with catheter-directed thrombolysis (CDT) within 21 days of onset were enrolled. An infusion catheter with multiple side holes was placed to cover the thrombosed vessel entirely. Urokinase solution was administered either continuously or with the pulse-spray method at a dose of 480,000-720,000 IU/day over the course of 2-7 days. During CDT, unfractionated heparin (UFH) was infused simultaneously via the access sheath to prevent thrombus formation. Early success was defined as lysis grade ≥ 50% and restoration of forward flow. PTS was diagnosed based on the Villalta scale. Based on the lysis grading method, complete lysis (grade III) was achieved in 8 of 52 (16%) limbs. Lysis grade II (50-99%) was achieved in 35 of 52 (67%) limbs. Lysis grade I (< 50%) was achieved in 9 of 52 (17%) limbs. Therefore, grade II and grade III lytic outcomes (early success) were observed in 43 patients (83%). One-year clinical follow-up was performed for 43 patients (83%). PTS occurred in seven (16%) patients. Early success was more frequently observed in patients without PTS than in those with PTS (92% vs. 43%; P < 0.01). Early success was only significantly associated with PTS in the multivariate analysis. Patients with acute symptomatic iliofemoral DVT who had early success from CDT treatment during the acute phase less frequently progressed to PTS. Patients with early success tended to undergo the pulse-spray method and had a shorter interval from symptom onset to CDT. The use of pulse-spray method and early initiation of CDT since DVT onset were potential markers of thrombolysis success.

Open-label multicenter registry on the outcomes of peripheral arterial disease treated by balloon angioplasty with optical frequency domain imaging in superficial femoral artery and popliteal artery (OCEAN-SFA study).

Although balloon angioplasty for femoropopliteal artery lesions has been associated with restenosis rates of up to 60% at 12 months, the mechanism of restenosis has not been fully evaluated. The aim of this study was to evaluate the relationship between the vascular features observed on optical frequency domain imaging (OFDI) before and after balloon angioplasty of femoropopliteal artery lesions, and restenosis at 6 months. This study was a prospective multicenter single arm study. OFDI was performed before and after balloon angioplasty and plaque characteristics and vascular features, along with de novo lesions, were assessed. The primary outcome was the presence or absence of restenosis 6 months after balloon angioplasty. Residual platelet reactivity was assessed according to VerifyNow platelet reactivity units (PRUs). The number of patients completing 6 months of follow-up was 47, of which 14 had developed restenosis. Maximum thickness of the dissection flap (odds ratio (OR) 2.71; 95% confidence interval [0.9-8.0]; p = 0.071) and lesion length were identified as risk factors for restenosis (OR 1.015; 95% confidence interval [0.001-0.029]; p = 0.039). The mean PRU at the time of treatment in patients with restenosis was significantly higher than in those without restenosis (286.3 ± 82.6 vs. 208.5 ± 03.6, p = 0.026). Long lesions and major dissection on OFDI after balloon angioplasty for femoropopliteal artery lesions increase restenosis at 6 months. In addition, high residual platelet reactivity at the time of EVT may also be a risk factor for restenosis.Clinical Trial Registration Number UMIN000021120.

Open-Label Multicenter Registry on the Outcomes of In-Stent Restenosis Treated by Balloon Angioplasty with Optical Frequency Domain Imaging in the Superficial Femoral Artery (ISLAND-SFA Study).

Objectives: Balloon angioplasty for in-stent restenosis (ISR) in the superficial femoral artery (SFA) has a high recurrent restenosis rate; however, its mechanism has not been fully and precisely evaluated using high-resolution intravascular imaging. Thus, we aimed to evaluate the relationship between vascular features obtained by optical frequency domain imaging (OFDI) and recurrent restenosis at 6 months. Methods: This was a prospective multicenter single-arm study. OFDI was performed before and after balloon angioplasty, and vascular features were assessed. A multi-layered ISR pattern detected by OFDI was defined as several signal-poor appearances with a high-signal band adjacent to the luminal surface. The primary outcome was defined as recurrent restenosis 6 months after balloon angioplasty. Results: Given that this study was terminated early, only 18 patients completed the 6-month follow-up; of these, 8 developed restenosis. Recurrent restenosis at 6 months tended to be related to a multi-layered ISR pattern (odds ratio (OR), 6.67; 95% confidence interval (CI), 0.81-54.96; p=0.078) and the minimum lumen area (MLA) after balloon angioplasty (OR, 0.71; 95%CI, 0.48-1.04; p=0.077). Conclusion: A multi-layered ISR pattern and MLA after balloon angioplasty detected by OFDI might be risk factors for recurrent ISR in the SFA.

Trans-aortic pulmonary vein isolation using magnetic navigation system for paroxysmal atrial fibrillation in a patient with dextrocardia, situs inversus, and inferior vena cava continuity with azygos vein.

A 51-year-old male with dextrocardia and situs inversus underwent catheter ablation for paroxysmal atrial fibrillation. Because the procedure through the trans-septal approach was impossible due to the inferior vena cava continuity with azygos vein, we performed pulmonary vein isolation using magnetic navigation system through the retrograde trans-aortic approach. Superior and inferior left-sided and superior right-sided pulmonary veins could be isolated which was confirmed by the ablation catheter. The patient was free from atrial fibrillation episode at the 12 months follow-up except only one palpitation episode lasting nearly 12 hours at 9 months after the ablation.

Efficacy of biolimus A9-eluting stent for treatment of right coronary ostial lesion with intravascular ultrasound guidance: a multi-center registry.

The aim of this study was to assess the efficacy of a biolimus A9-eluting stent in patients with a right coronary artery (RCA) ostial lesion. Ostial lesions of the RCA have been a limitation of percutaneous coronary intervention even in the drug-eluting stent (DES) era. However, clinical outcomes after the deployment of a second generation DES to an RCA ostial lesion with intravascular ultrasound (IVUS) guidance have not been fully elucidated. From September 2011 to March 2013, 74 patients were enrolled in 17 centers from Japan. RCA ostial lesion was defined as de novo significant stenotic lesion located within 15 mm from ostium. IVUS was used for all cases to confirm the location of ostium and evaluate stent coverage of ostium. Patients with hemodialysis were excluded. The primary endpoint is a major adverse cardiac event (MACE) at 1 year. Forty two percent of patients had multi-vessel disease. Angiographically severe calcification was observed in 26% of the lesions. The mean stent diameter was 3.3 ± 0.3 mm (3.5 mm, 72%, 3.0 mm, 25%, and 2.75 and 2.5 mm, 3%), stent length was 17.5 ± 5.8 mm, and dilatation pressure of stenting was 15.6 ± 4.1 atm. RCA ostium was covered by stent in all lesions in IVUS findings. Post dilatation was performed for 64% of lesions (balloon size 3.7 ± 0.6 mm). MACE rate at 1 year was 5.4% (target lesion revascularization 5.4%, myocardial infarction 1.2%, and no cardiac death). The biolimus A9-eluting stent for RCA ostial lesions with IVUS guidance showed favorable results at 1-year follow-up.

Dual Antiplatelet Therapy for 6 Versus 18 Months After Biodegradable Polymer Drug-Eluting Stent Implantation.

OBJECTIVES: The NIPPON (Nobori Dual Antiplatelet Therapy as Appropriate Duration) study was a multicenter randomized investigation of the noninferiority of short-term versus long-term dual antiplatelet therapy (DAPT) in patients with implantation of the Nobori drug-eluting stent (DES) (Terumo, Tokyo, Japan), which has a biodegradable abluminal coating. BACKGROUND: The optimum duration of DAPT for patients with a biodegradable polymer-coated DES is unclear. METHODS: The subjects were 3,773 patients with stable or acute coronary syndromes undergoing Nobori stent implantation. They were randomized 1:1 to receive DAPT for 6 or 18 months. The primary endpoint was net adverse clinical and cerebrovascular events (NACCE) (all-cause mortality, myocardial infarction, stroke, and major bleeding) from 6 to 18 months after stenting. Intention-to-treat analysis was performed in 3,307 patients who were followed for at least 6 months. RESULTS: NACCE occurred in 34 patients (2.1%) receiving short-term DAPT and 24 patients (1.5%) receiving long-term DAPT (difference 0.6%, 95% confidence interval [CI]: 1.5 to 0.3). Because the lower limit of the 95% CI was inside the specified margin of -2%, noninferiority of short-term DAPT was confirmed. Mortality was 1.0% with short-term DAPT versus 0.4% with long-term DAPT, whereas myocardial infarction was 0.2% versus 0.1%, and major bleeding was 0.7% versus 0.7%, respectively. The estimated probability of NACCE was lower in the long-term DAPT group (hazard ratio: 1.44, 95% CI: 0.86 to 2.43). CONCLUSIONS: Six months of DAPT was not inferior to 18 months of DAPT following implantation of a DES with a biodegradable abluminal coating. However, this result needs to be interpreted with caution given the open-label design and wide noninferiority margin of the present study. (Nobori Dual Antiplatelet Therapy as Appropriate Duration [NIPPON]; NCT01514227).

Two-year clinical outcome in patients with small coronary artery disease treated with everolimus- versus paclitaxel-eluting stenting.

BACKGROUND: Percutaneous coronary interventions involving small coronary vessels represent a true challenge because of the increased risk of restenosis and adverse outcomes. We evaluated the 2-year clinical outcomes between single everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in small coronary artery disease. METHODS: From the data of SACRA (SmAll CoronaRy Artery treated by TAXUS Liberté) and PLUM (PROMUS/Xience V Everolimus-ELUting Coronary Stent for sMall coronary artery disease) registries, 245 patients with 258 lesions and 264 patients with 279 lesions, respectively, were enrolled in this study. RESULTS: The 2-year clinical driven target lesion revascularization (4.5% vs. 10.6%, p=0.01) and target vessel revascularization (8.0% vs. 13.9%, p=0.03) rates were significantly lower in the EES group compared with the PES group. Major adverse cardiac events in the EES group tended to be lower than those in the PES group (8.7% vs. 14.3%, p=0.05). On the other hand, all new lesions for remote target vessel revascularization were observed at the proximal site of target lesions in both groups and those rates were not different between the two groups (3.4% vs. 3.3%, p>0.99). CONCLUSION: EES showed better clinical results at 2-year follow-up compared with PES in small coronary artery diseases, however, new lesions at the proximal remote site of the target lesion remain problematic.

Expression of Toll-like receptors on human platelets.

INTRODUCTION: Platelets play a crucial role in arterial thrombosis, which is the main cause of acute coronary syndrome. Some mycobacteriums, such as Chlamydia pneumoniae, were associated with progression of atherosclerosis and they are interacted with Toll-like receptors (TLRs), which have been defined as pathogen-associated molecular pattern recognition molecules in innate immunity. In the present study, we examined whether human platelets express TLRs. MATERIALS AND METHODS: Human platelets were obtained from healthy volunteers and the mRNA and protein level of TLRs on platelets and Meg-01 cells, megakaryoblastic cell line, were investigated. RESULTS: Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that TLR1 and TLR6 mRNA were expressed in platelets and Meg-01 cells. Furthermore, interferon-gamma up-regulated their mRNA levels in dose and time dependent manners after stimuli. Both TLR1 and TLR6 proteins in platelets were detected by Western blotting, and their expression of platelets was more than that of Meg-01 cells. Flow cytometry analysis revealed the expression of TLR1 and TLR6 on the cell surface of Meg-01 cells. Furthermore, immunohistochemical analysis using human coronary thrombi obtained from patients with acute coronary syndrome confirmed the expression of TLR1 and TLR6 on platelets. CONCLUSION: In summary, we demonstrated that human platelets and Meg-01 cells expressed a family of TLRs for the first time, and our findings indicated that platelets might recognize antigens directly via TLRs. Our findings suggest a possibility that platelets have the ability to recognize the antigens via TLRs and that there are mechanistic relations between infectious inflammation and atherosclerotic vascular diseases.

A randomized comparison of sirolimus- vs. paclitaxel-eluting stents for treatment of bifurcation lesions by single stent and kissing balloon: results of the SINGLE KISS trial.

BACKGROUND: In the treatment of bifurcation lesions, routine stenting of both branches has thus far failed to demonstrate a clear clinical advantage over a provisional one-stent strategy. On the other hand, large scale data evaluating different stent types for clinical outcomes after one-stent treatment with final kissing inflation (FKI) of bifurcation lesions is also limited. This prospective study evaluated the clinical and angiographic outcomes of paclitaxel-eluting stents (PES) vs. sirolimus-eluting stents (SES) in single crossover main branch stenting followed by FKI in patients with bifurcation lesions. METHODS: We randomized 800 patients with single bifurcation lesions to PES (n=400) and SES (n=400) groups. RESULTS: Crossover rates to the two-stent strategy were low in both groups (PES 1.5%, SES 2.8%; p=0.23). At 1 year, there was no significant difference in the primary endpoint of this study, target lesion revascularization rate (PES 3.8%, SES 3.2%, hazard ratio 0.83; 95% confidence interval 0.39 to 1.76; p=0.62). Stent thrombosis occurred in only 1 case in the SES group after 282 days. At 9 months, a total of 593 patients underwent quantitative coronary measurement. The main branch restenosis rate in the PES group was significantly higher than that of the SES group (PES 12.2%, SES 5.5%; p=0.004), however both groups exhibited similar high side branch restenosis rates (PES 17.2%, SES 19.3%; p=0.6). CONCLUSIONS: In patients with bifurcation lesions, a single stent strategy using PES and SES with FKI indicated similar 1 year clinical outcomes and safety profiles.