Impact of intravascular ultrasound-guided endovascular therapy on periprocedural outcomes in patients with lower-extremity artery disease.

BACKGROUND: Although technological improvements in intravascular ultrasound (IVUS) may reduce technical failures in endovascular therapy (EVT), perioperative complications (POCs) associated with IVUS use may increase. AIMS: This study investigated the impact of IVUS on periprocedural outcomes in symptomatic lower-extremity artery disease (LEAD) patients undergoing EVT. METHODS: This study evaluated 28,088 symptomatic LEAD patients who underwent EVT between January 2021 and December 2021 using a prospective nationwide registry in Japan. Outcome measures included periprocedural outcomes, including technical failure and POCs. To compare outcomes with and without IVUS use, propensity score matching analysis was performed for overall and for each arterial region (aortoiliac [AI], femoropopliteal [FP], and infrapopliteal [IP] arteries) using a binary logistic regression model. RESULTS: IVUS was used in 75%, 72%, and 37% of AI, FP, and IP lesions, respectively. After propensity matching extraction, the IVUS group had a tendency of lower technical failure rate than the non-IVUS group, although not statistically different (3.9% vs. 5.4%, p = 0.054), without an increase in the POC rate (1.8% vs. 1.6%, p = 0.54). Regarding the per-regional analysis, the technical failure rate of FP-EVT was significantly lower in the IVUS group (3.1% vs. 4.2%, p = 0.006), whereas those of AI-EVT (2.2% vs. 3.1%, p = 0.12) and IP-EVT (6.8% vs. 6.1%, p = 0.37) were not significantly different between the two groups. Furthermore, IVUS did not increase the POC rate for any region (AI-EVT: 1.3% vs. 1.3%, p = 1.00; FP-EVT: 1.8% vs. 1.7%, p = 0.75; and IP-EVT: 2.0% vs. 1.7%, p = 0.56). CONCLUSION: The current study revealed that IVUS did not increase the POCs and technical failure for overall lesions but reduced the incidence of FP-EVT technical failure.

Impact of Sex Differences on Clinical Outcomes in Patients Following Primary Revascularization for Acute Myocardial Infarction　- Insights From the Japanese Nationwide Registry.

BACKGROUND: Women with acute myocardial infarction (AMI) often present a worse risk profile and experience a higher rate of in-hospital mortality than men. However, sex differences in post-discharge prognoses remain inadequately investigated. We examined the impact of sex on 1-year post-discharge outcomes in patients with AMI undergoing percutaneous coronary intervention.Methods and Results: We extracted patient-level data for the period January 2017-December 2018 from the J-PCI OUTCOME Registry, endorsed by the Japanese Association of Cardiovascular Intervention and Therapeutics. One-year all-cause and cardiovascular mortality and major adverse cardiovascular events were compared between men and women. In all, 29,856 AMI patients were studied, with 6,996 (23.4%) being women. Women were significantly older and had a higher prevalence of comorbidities than men. Crude all-cause mortality was significantly higher among women than men (7.5% vs. 5.4% [P<0.001] for ST-elevation myocardial infarction [STEMI]; 7.0% vs. 5.2% [P=0.006] for non-STEMI). These sex-related differences in post-discharge outcomes were attenuated after stratification by age. Multivariate analysis demonstrated an increase in all-cause mortality in both sexes with increasing age and advanced-stage chronic kidney disease (CKD). CONCLUSIONS: Within this nationwide cohort, women had worse clinical outcomes following AMI than men. However, these sex-related differences in outcomes diminished after adjusting for age. In addition, CKD was significantly associated with all-cause mortality in both sexes.

The Absorb GT1 Bioresorbable Vascular Scaffold System　- 5-Year Post-Market Surveillance Study in Japan.

BACKGROUND: The 1-year clinical outcomes of the Absorb GT1 Japan post-market surveillance (PMS) suggested that an appropriate intracoronary imaging-guided bioresorbable vascular scaffold (BVS) implantation technique may reduce the risk of target lesion failure (TLF) and scaffold thrombosis (ST) associated with the Absorb GT1 BVS. The long-term outcomes through 5 years are now available.Methods and Results: This study enrolled 135 consecutive patients (n=139 lesions) with ischemic heart disease in whom percutaneous coronary intervention (PCI) with the Absorb GT1 BVS was attempted. Adequate lesion preparation, imaging-guided appropriate sizing, and high-pressure post-dilatation using a non-compliant balloon were strongly encouraged. All patients had at least 1 Absorb GT1 successfully implanted at the index procedure. Intracoronary imaging was performed in all patients (optical coherence tomography: 127/139 [91.4%] lesions) and adherence to the implantation technique recommendations was excellent: predilatation, 100% (139/139) lesions; post-dilatation, 98.6% (137/139) lesions; mean (±SD) post-dilatation pressure, 18.8±3.5 atm. At 5 years, the follow-up rate was 87.4% (118/135). No definite/probable ST was reported through 5 years. The cumulative TLF rate was 5.1% (6/118), including 2 cardiac deaths, 1 target vessel-attributable myocardial infarction, and 3 ischemia-driven target lesion revascularizations. CONCLUSIONS: Appropriate intracoronary imaging-guided BVS implantation, including the proactive use of pre- and post-balloon dilatation during implantation may be beneficial, reducing the risk of TLF and ST through 5 years.

Clinical efficacy of tolvaptan in acute decompensated heart failure patients with severe aortic stenosis and atrial fibrillation: a sub-analysis from the LOHAS registry.

BACKGROUND: Severe aortic valve stenosis (AS) and atrial fibrillation (AF) are risk factors of hemodynamic instability in heart failure (HF) management due to low cardiac output, respectively. Therefore, the treatment of HF due to severe AS complicated with AF is anticipated to be difficult. Tolvaptan, a vasopressin V2 receptor inhibitor, is effective in controlling acute decompensated heart failure (ADHF) with hemodynamic stability. However, its clinical efficacy against ADHF caused by AS with AF remains to be determined. METHODS: Clinical information (from September 2014 to December 2017) of 59 patients diagnosed with ADHF due to severe AS (20 patients with AF; 39 patients with sinus rhythm [SR]) was obtained from the LOHAS registry. The registry collected data from seven hospitals and assessed the short-term effects of tolvaptan in patients hospitalized for ADHF with severe AS. We attempted to identify clinical differences from baseline up to 4 days, comparing patients with AF (AF group) versus those with SR (SR group). RESULTS: There were no significant differences between the groups in age (83.7 ± 4.5 vs. 85.8 ± 6.9 years, respectively; p = 0.11) and aortic valve area (0.60 [0.46-0.73] vs. 0.56 [0.37-0.70] cm2, respectively; p = 0.50). However, left atrial volume was larger (104 [85-126] vs. 87 [64-103] mL, respectively; p < 0.01), whereas stroke volume was lower (51.6 ± 14.8 vs. 59.0 ± 18.7 mL, respectively; p = 0.08) in the AF group versus the SR group. Body weight decreased daily from baseline up to day 4 in both groups (from 55.4 to 53.2 kg [p < 0.01] and from 53.5 to 51.0 kg [p < 0.01], respectively) without change in heart rate. Notably, the systolic blood pressure decreased slightly in the AF group after 2 days of treatment with tolvaptan. CONCLUSIONS: Short-term treatment with tolvaptan improved HF in patients hospitalized for severe AS, regardless of the presence of AF or SR. After achieving sufficient diuresis, a slight decrease in blood pressure was observed in the AF group, suggesting an appropriate timeframe for safe and effective use of tolvaptan.

Characteristics and outcomes of patients with no standard modifiable risk factors undergoing primary revascularization for acute myocardial infarction: Insights from the nationwide Japanese percutaneous coronary intervention registry.

BACKGROUND: Identification of and therapeutic approaches to standard modifiable risk factors (SMuRFs), including hypertension, diabetes, dyslipidemia, and smoking, have led to improved survival of patients at risk for coronary events. However, recent studies have indicated that a significant proportion of patients with acute myocardial infarction (AMI) have no SMuRFs. We aimed to assess in-hospital outcomes and the prevalence of these patients using the Japanese nationwide percutaneous coronary intervention (J-PCI) registry. METHODS: The J-PCI is a procedure-based registration program in Japan. A total of 115,437 PCI procedures were performed on patients with AMI between January 2019 and December 2020. The participants were divided into 2 groups: those with at least 1 SMuRF and those without any SMuRFs. The primary outcome was in-hospital mortality. RESULTS: Of the 115,437 patients with AMI, 1,777 (1.6%) had no SMuRFs. Patients without SMuRFs were older; more likely to have left main disease; and more likely to present with heart failure, cardiogenic shock, and cardiac arrest than those with SMuRFs, resulting in higher rates of mechanical circulatory support use and impaired post-PCI coronary blood flow. In-hospital mortality was significantly higher in patients without SMuRFs than in those with SMuRFs (18.3% vs 5.3%, P < .001), irrespective of the presence or absence of ST-segment elevation. CONCLUSIONS: In Japan, where annual health checks are mandated under universal health care coverage, the vast majority of patients with AMI undergoing PCI have SMuRFs. However, although small in number, patients without SMuRFs are more likely to present with life-threatening conditions and have worse in-hospital survival.

One-year outcomes of patients undergoing percutaneous coronary intervention with the revived directional coronary atherectomy catheter: Insights from the J-PCI OUTCOME registry.

OBJECTIVES: We sought to investigate the 1-year outcomes, including all-cause and cardiovascular mortality, major adverse cardiovascular events (MACEs), and major bleeding, of patients undergoing percutaneous coronary intervention (PCI) with or without the revived directional coronary atherectomy (DCA) catheter in a Japanese nationwide registry. BACKGROUND: Clinical data regarding the midterm outcomes of patients undergoing PCI with DCA are scarce in contemporary real-world practice. METHODS: We analyzed the data of 74,764 patients who underwent PCI at 179 hospitals from January 2017 to December 2018. The baseline characteristics and 1-year outcomes of patients with stable coronary artery disease or unstable angina who underwent PCI with or without DCA were assessed. RESULTS: Overall, 431 patients (0.6%) underwent PCI with DCA. Patients in the DCA group were younger and predominantly male, with fewer comorbidities than patients in the non-DCA group. Stentless PCI with DCA following additional drug-coated balloon (DCB) angioplasty was the dominant strategy in the DCA group (43.6%). One-year outcomes, including all-cause mortality (1.2% in the DCA group vs. 2.5% in the non-DCA group, respectively, p = 0.075), cardiovascular death (0.9% vs. 1.0%, p = 0.69), MACEs (1.9% vs. 1.8%, p = 0.96), and nonfatal major bleeding requiring readmission (1.2% vs. 1.4%, p = 0.62), were comparable between the two groups. In the DCA group, 1-year outcomes were comparable, regardless of whether the stent or DCB was used. CONCLUSIONS: One-year clinical outcomes after PCI with DCA in patients with stable coronary artery disease or unstable angina are acceptable, regardless of stent use.

Ten-year clinical outcomes from a randomized trial comparing new-generation everolimus-eluting stent versus first-generation Sirolimus-eluting stent: Results from the RESET extended study.

BACKGROUND: New-generation drug-eluting stents (DES) achieved technological innovations and reported clinical advantages as compared with first-generation DES in clinical trials with 3-5 years follow-up. However, detailed clinical outcome data in very long-term follow-up is still scarce. OBJECTIVES: To evaluate 10-year clinical outcomes after first- and new-generation DES implantation. METHODS: In this extende follow-up study of the RESET, which is a largest randomized trial comparing everolimus-eluting stent (EES) with Sirolimus-eluting stent (SES), the study population consisted of 2892 patients from 84 centers. The primary efficacy and safety endpoints were target lesion revascularization (TLR) and a composite of death or myocardial infarction (MI), respectively. Complete 10-year follow-up was achieved in 87.9% of patients. RESULTS: Cumulative 10-year incidences of TLR and non-TLR were not significantly different between EES and SES (13.9% vs. 15.7%, Log-rank p = 0.20, and 33.4% vs. 31.3%, Log-rank p = 0.30). The cumulative 10-year incidence of death/MI was also not significantly different between the groups (32.5% vs. 34.4%, Log-rank p = 0.18). Cumulative 10-year incidence of definite stent thrombosis was numerically lower in EES than in SES (1.0% vs. 1.7%, Log-rank p = 0.16). The lower risk of EES relative to SES was significant for a composite endpoint of target lesion failure (TLF: 19.6% vs. 24.9%, Log-rank p = 0.001) and target vessel failure (TVF: 26.7% vs. 31.4%, Log-rank p = 0.006). CONCLUSION: During 10-year of follow-up, the risks for primary efficacy and safety endpoints were not significantly different between new-generation EES and first-generation SES, although EES compared with SES was associated with a lower risk for composite endpoints such as TLF and TVF.

Comparing the Safety and Feasibility of Endovascular Therapy via Transradial and Transfemoral Approaches in Patients with Aortoiliac Occlusive Disease: A Propensity Score-Matched Analysis of the Nationwide Registry.

PURPOSE: Our objective was to evaluate the feasibility of performing endovascular therapy (EVT) for aortoiliac artery disease using transradial approach (TRA) as compared to transfemoral approach (TFA). METHODS: We analyzed 9671 cases with symptomatic lower extremity artery disease due to aortoiliac occlusive disease (AIOD) treated using EVT from a Japanese Nationwide EVT Registry between January and December 2021. We compared the baseline characteristics, procedural information, and 30-day outcomes of patients who received EVT only via TRA (n=863 [16.9%]) and those only via TFA (n=4255 [83.1%]) by using propensity score (PS) matching, after excluding those who required regular dialysis, those who underwent hybrid surgeries, and those who received EVT through 2 or more approach sites. RESULTS: After matching, the final study population consisted of 862 matched patients with similar baseline characteristics in each group. Technical success rate was comparable between the 2 groups (99.3% vs. 99.3%, p>0.99). No significant differences were observed with respect to the composite of all-cause death within 48 hours after EVT and post-procedural complications within 30 days, including severe bleeding that required transfusion, revascularization procedures, urgent surgeries, cerebral infarction, and major limb amputation (0.2% vs. 0.7%, p=0.29). Transradial approach was associated with shorter operation time (85 vs. 90 minutes, p=0.016), but longer fluoroscopy time (26 vs. 20 minutes, p<0.001) and higher contrast agent volume (80 vs. 75 mL, p<0.001). CONCLUSION: After PS matching, TRA showed the comparable rates of successful EVT and 30-day complications in patients with AIOD compared to TFA. Transradial approach was found to be safe and be a viable alternative of TFA for the treatment of AIOD. CLINICAL IMPACT: The efficacy of transradial approach (TRA) is established in percutaneous coronary intervention; however, its safety and feasibility are unclear in endovascular therapy (EVT). We analyzed 9,671 cases with symptomatic aortoiliac occlusive disease treated using EVT from a Nationwide Registry to compare the 30-day outcomes of those who received EVT only via TRA (n = 863 [16.9%]and those only via TFA (n=4,255 [83.1%]) by using propensity score matching. Technical success rate (99.3% vs. 99.3%, p > 0.99) and 30-day complications (0.2% vs. 0.7%, p = 0.29) were comparable between the two groups. EVT via TRA could be performed safely.

Prediction of Slow-Flow Phenomenon After Stent Implantation Using Near-Infrared Spectroscopy in Patients With Acute and Chronic Coronary Syndrome.

BACKGROUND: The slow-flow phenomenon is associated with worse clinical outcomes after percutaneous coronary intervention (PCI), so our goal for this study was to see how predictive how near-infrared spectroscopy (NIRS) could be.Methods and Results: We enrolled 179 lesions from 152 patients who had de novo coronary stent implantation guided by NIRS-intravascular ultrasound (IVUS) (male: 69.1%, mean age: 74.3±11.5 years, acute coronary syndrome: 65.1%, diabetes: 42.1%). NIRS automatically determined the maximum 4-mm lipid core burden index (maxLCBI4 mm) value at pre- and post-PCI procedures. The slow-flow phenomenon was defined as the deterioration of TIMI (Thrombolysis in Myocardial Infarction) flows on angiography during the PCI procedure in the absence of mechanical obstruction. The slow-flow phenomenon occurred in 13 (7.3%) lesions, and the slow-flow phenomenon group had a significantly higher maxLCBI4 mm(740±147 vs. 471±223, P<0.001). The best maxLCBI4 mmcutoff point in both acute and chronic coronary syndrome was 578 and 480, with sensitivity of 100%, for predicting the slow-flow phenomenon. In the receiver-operating characteristics analysis, the area under the curve for acute and chronic coronary syndrome was 0.849 and 0.851, respectively. CONCLUSIONS: The results of this study support the utility of NIRS-IVUS-guided PCI for the prediction of the slow-flow phenomenon.

Drug-Coated Balloon for the Treatment of Small Vessel Coronary Artery Disease　- A Randomized Non-Inferiority Trial.

BACKGROUND: Drug-coated balloons (DCB) have shown promising results for the treatment of in-stent restenosis (ISR) and small vessel disease (SVD). However, data comparing the treatment efficacy of different DCBs are limited.Methods and Results: AGENT Japan is a prospective randomized controlled trial that compares the Agent balloon coated with a low-dose formulation of paclitaxel (2 µg/mm2) to the SeQuent Please paclitaxel-coated balloon (3 µg/mm2) for the treatment of SVD. Patients with target lesion length ≤28 mm and reference diameter between ≥2.00 and <3.00 mm were randomized 2 : 1 for treatment with Agent (n=101) or SeQuent Please (n=49). This trial also includes a separate single-arm substudy evaluating the clinical safety and effectiveness of Agent in patients with ISR. The primary endpoint of 6-month target lesion failure (TLF) was observed in 3.0% of Agent and 0.0% of SeQuent Please patients (difference=3.0%; 97.5% upper confidence bound [UCB]=9.57%, which is less than the prespecified margin of 13.2%; Pnon-inferiority=0.0012). There were no deaths or thrombosis, and angiographic and quality-of-life outcomes were comparable between groups. The AGENT Japan ISR substudy (n=30) primary endpoint was met because the one-sided 97.5% UCB for 6-month TLF (3.3%) was significantly less than the study success criterion of 15.1% (97.5% UCB=9.8%; P<0.0001). CONCLUSIONS: Data from this study demonstrate good clinical outcomes with the Agent DCB when used to treat patients with SVD or ISR.

Prasugrel Monotherapy After Percutaneous Coronary Intervention With Biodegradable-Polymer Platinum-Chromium Everolimus Eluting Stent for Japanese Patients With Chronic Coronary Syndrome (ASET-JAPAN).

BACKGROUND: P2Y12 inhibitor monotherapy without aspirin immediately after percutaneous coronary intervention (PCI) has not been tested in East Asian patients, so in this study we aimed to assess the safety and feasibility of reduced dose (3.75 mg/day) prasugrel monotherapy in Japanese patients presenting with chronic coronary syndrome (CCS).Methods and Results: ASET-JAPAN is a prospective, multicenter, single-arm pilot study that completed enrolment of 206 patients from 12 Japanese centers in September 2022. Patients with native de-novo coronary lesions and a SYNTAX score <23 were treated exclusively with biodegradable-polymer platinum-chromium everolimus-eluting stent(s). Patients were loaded with standard dual antiplatelet therapy (DAPT) and following successful PCI and optimal stent deployment, they received low-dose prasugrel (3.75 mg/day) monotherapy for 3 months. The primary ischemic endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction, or definite stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5. At 3-month follow-up, there were no primary bleeding or ischemic events, or any stent thrombosis. CONCLUSIONS: This pilot study showed the safety and feasibility of prasugrel monotherapy in selected low-risk Japanese patients with CCS. This "aspirin-free" strategy may be a safe alternative to traditional DAPT following PCI.

Validation of reliability and predictivity of membrane septum length measurements for pacemaker need after transcatheter aortic valve replacement.

OBJECTIVES: To assess the inter methodological agreement of membrane septum (MS) length measurement and additive value for risk stratification of new pacemaker implantation (PMI) over the established predictors after transcatheter aortic valve replacement (TAVR). BACKGROUND: Recent studies have suggested MS length and implantation depth (ID) as predictors for PMI after TAVR. However, the measurement of MS length is neither uniform nor validated in different cohort. METHODS: We retrospectively analyzed patients who underwent TAVR at five centers. The MS length was measured by two previously proposed methods (coronal and annular view method). Predictive ability of risk factors, including MS length and ID, for new PMI within 30 days after TAVR were evaluated. RESULTS: Among 754 patients of study population, 31 patients (4.1%) required new PMI within 30 days of TAVR. There was a weak correlation (ρ = 0.47) and a poor agreement between the two methods. The ID and the difference between MS length and ID (ΔMSID), were independent predictors for new PMI, whereas MS length alone was not. Further, for predicting new PMI after TAVR, discrimination performance was not significantly improved when MS length was added to the model with ID alone (integrated discrimination improvement = 0, p= 0.99; continuous net-reclassification improvement = 0.10, p= 0.62). CONCLUSIONS: External validity and predictive accuracy of MS length for PMI after TAVR were not sufficient to provide better risk stratification over the established predictors in our cohort. Moreover, the ID and ΔMSID, but not MS length alone, are predictive of future PMI after TAVR.

Effect of proximal optimization technique on coronary bifurcation stent failure: Insights from the multicenter randomized PROPOT trial.

OBJECTIVE: We investigated the effect of proximal optimization technique (POT) on coronary bifurcation stent failure (BSF) in cross-over stenting by comparing with the kissing balloon technique (KBT) in a multicenter randomized PROPOT trial. BACKGROUND: POT is recommended due to increased certainty for optimal stent expansion and side branch (SB) wiring. METHODS: We randomized 120 patients treated with crossover stenting into the POT group, which was followed by SB dilation (SBD), and the KBT group. Finally, 52 and 57 patients were analyzed by optical coherence tomography before SBD and at the final procedure, respectively. Composite BSF was defined as a maximal malapposition distance of >400 µm, or malapposed and SB-jailed strut rates of >5.95% and >21.4%, respectively. RESULTS: Composite BSF before SBD in the POT and KBT groups was observed in 29% and 26% of patients, respectively. In the POT group, differences in stent volumetric index between the proximal and distal bifurcation (odds ratio [OR] 60.35, 95% confidential interval [CI] 0.13-0.93, p = 0.036) and between the proximal bifurcation and bifurcation core (OR: 3.68, 95% CI: 1.01-13.40, p = 0.048) were identified as independent risk factors. Composite BSF at final in 27% and 32%, and unplanned additional procedures in 38% and 25% were observed, respectively. Composite BSF before SBD was a risk factor for the former (OR: 6.33, 95% CI: 1.10-36.50, p = 0.039) and the latter (OR: 6.43, 95% CI: 1.25-33.10, p = 0.026) in the POT group. CONCLUSION: POT did not result in a favorable trend in BSF. Insufficient expansion of the bifurcation core after POT was associated with BSF.

Clinical Outcomes After Percutaneous Coronary Intervention in East Asian Patients　- 30-Month Results of the PENDULUM Registry.

BACKGROUND: The 12-month results of the PENDULUM registry showed that after implantation of second-generation drug-eluting stents (DES), high P2Y12reaction unit (HPR) were independently associated with ischemic but not bleeding events.Methods and Results: This study analyzed cumulative incidences of major adverse cardiac and cerebrovascular events (MACCE) and major bleeding (Bleeding Academic Research Consortium type 3 and 5) at 30 months after index percutaneous coronary intervention (PCI) (primary endpoints). Of 6,422 patients undergoing PCI with DES, 5,796 completed the 30-month follow up. The continuation rate of dual antiplatelet therapy decreased to 59.3% at 12 months and 26.4% at 30 months. At 30 months, the cumulative incidence of MACCE increased linearly and reached 9.5% (95% confidence interval 8.8-10.2) and that of major bleeding had the inflection point at 12 months and was 4.4% (3.9-5.0). MACCE and bleeding events were higher in HPR patients (unadjusted P value). After covariate adjustment, P2Y12reactivity units measured immediately after index PCI was not an independent risk factor for MACCE or major bleeding at 30 months. CONCLUSIONS: MACCE consistently increased after 12 months post-PCI, whereas the increase in major bleeding events slowed down after 12 months in Japanese PCI patients in a real-world clinical setting. HPR patients had increased MACCE and bleeding complications, but HPR was not an independent risk factor of events at 30 months.

Early P2Y12 Inhibitor Single Antiplatelet Therapy for High-Bleeding Risk Patients After Stenting　- PENDULUM Mono 24-Month Analysis.

BACKGROUND: In PENDULUM mono, Japanese patients with high bleeding risk (HBR) received short-term dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) with prasugrel after percutaneous coronary intervention (PCI). One-year data from PENDULUM mono showed better outcomes with prasugrel monotherapy after short-term DAPT compared with matched patients in the PENDULUM registry with longer DAPT durations according to guidelines at that time. This study presents 2-year results.Methods and Results: We compared 24-month data from PENDULUM mono (n=1,107; de-escalation strategy group) and the PENDULUM registry (n=2,273; conventional strategy group); both were multicenter, non-interventional, prospective registry studies, using the inverse probability of treatment weighting (IPTW) method. In the PENDULUM mono group, the cumulative incidence of clinically relevant bleeding (CRB) at 24 months post-PCI (primary endpoint) was 6.8%, and that of major adverse cardiac and cerebrovascular events (MACCE) was 8.9%. After IPTW adjustment, the cumulative incidence of CRB was 5.8% and 7.2% in PENDULUM mono and the PENDULUM registry, respectively (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.57-1.04; P=0.086), and that of MACCE was 8.0% and 9.5%, respectively (HR 0.77; 95% CI 0.59-1.01; P=0.061). CONCLUSIONS: Japanese PCI patients with HBR prescribed prasugrel SAPT after short-term DAPT had a lower ischemic event risk than those prescribed long-term DAPT, and this was particularly relevant for ischemic events after 1 year.

Ischemic and Bleeding Events in PENDULUM Patients With High Bleeding Risk and High Platelet Reactivity.

BACKGROUND: The balance between thrombotic and bleeding risk is of great concern in high bleeding risk (HBR) patients. This study evaluated the relationship between perioperative antiplatelet reactivity and thrombotic and bleeding events in patients at HBR undergoing percutaneous coronary intervention (PCI).Methods and Results: In this post hoc analysis of the PENDULUM (Platelet rEactivity in patieNts with DrUg eLUting stent and balancing risk of bleeding and ischeMic event) registry, patients undergoing PCI were categorized as HBR or non-HBR, and stratified as having high platelet reactivity (HPR; P2Y12reaction unit [PRU] >208) or non-HPR (PRU ≤208). Cumulative incidences of cardiovascular and cerebrovascular events (Journal of the American College of Cardiology expert definitions) and bleeding events (Bleeding Academic Research Consortium criteria) were assessed 12 months after index PCI. The incidence of ischemic and bleeding events was ~3-fold higher in HBR vs. non-HBR patients. Thrombotic/ischemic events were significantly more common in the HPR subgroup in HBR patients (hazard ratio [HR]: 1.59; 95% confidence interval [CI]: 1.11-2.28; P=0.012), but there was no difference in non-HBR patients. After adjustment for covariates, HPR in HBR patients remained an independent factor for thrombotic and ischemic events (HR: 1.69; 95% CI: 1.13-2.54; P=0.011), but not for bleeding events (HR: 1.56; 95% CI: 0.78-3.11; P=0.210). CONCLUSIONS: Maintaining adequate PRU levels during PCI is an important factor in improving clinical outcomes, especially for HBR patients.

Effect of oral tolvaptan for 1 year in patients with functional mitral regurgitation.

The effect of the oral selective vasopressin V2-receptor antagonist tolvaptan for chronic phase therapy on patients with FMR remains unclear. We aimed to determine the efficacy of oral tolvaptan in patients with significant functional mitral regurgitation (FMR) to reduce the mortality and rehospitalization due to worsening heart failure (HF). We enrolled 219 patients (mean age 76 ± 9 years, 59.4% men) who were admitted at our hospital due to congestive HF during different two 1-year periods. The patients were divided into 2 groups: those who had significant FMR (MR ≥ grade 2 [n = 76]) and those who did not (MR < grade 2 [n = 143]) at discharge. The patients were further divided into a study group that received tolvaptan during follow-up and a control group that did not receive tolvaptan. We used an inverse probability of treatment weighting method with the primary end point defined as overall all-cause mortality and rehospitalization due to worsening HF within 1 year. Of the 76 patients with significant FMR at discharge, 2 of 20 (10%) who were administered tolvaptan died and 8 (40%) were readmitted to a hospital. Of the 56 patients who did not receive tolvaptan, 2 (3.5%) died and 18 (27.5%) required rehospitalization. After multiple adjustments, there were no significant differences for overall survival and rehospitalization between the groups (log-rank p = 0.700 and 0.510, respectively). Our results suggest that oral tolvaptan administration in addition to conventional diuretics had less impact on outcomes in patients with significant FMR.

Relationship between platelet aggregation and stroke risk after percutaneous coronary intervention: a PENDULUM analysis.

In patients undergoing percutaneous coronary intervention (PCI) with a stent, high on-treatment platelet reactivity may be associated with an increased risk of stroke. This post hoc analysis of the PENDULUM registry compared the risk of post-PCI stroke according to on-treatment P2Y12 reaction unit (PRU) values. Patients aged ≥ 20 years who underwent PCI were stratified by baseline PRU (at 12 and 48 h post-PCI) as either high (HPR, > 208), optimal (OPR, > 85 to ≤ 208), or low on-treatment platelet reactivity (LPR, ≤ 85). The incidences of non-fatal ischemic and non-ischemic stroke through to 12 months post-PCI were recorded. Almost all enrolled patients (6102/6267 [97.4%]) had a risk factor for ischemic stroke, and most were receiving dual antiplatelet therapy. Of the 5906 patients with PRU data (HPR, n = 2227; OPR, n = 3002; LPR, n = 677), 47 had a non-fatal stroke post-PCI (cumulative incidence: 0.68%, ischemic; 0.18%, non-ischemic stroke). Patients with a non-fatal ischemic stroke event had statistically significantly higher post-PCI PRU values versus those without an event (P = 0.037). The incidence of non-fatal non-ischemic stroke was not related to PRU value. When the patients were stratified by PRU ≤ 153 versus > 153 at 12-48 h post-PCI, a significant difference was observed in the cumulative incidence of non-fatal stroke at 12 months (P = 0.044). We found that patients with ischemic stroke tended to have higher PRU values at 12-48 h after PCI versus those without ischemic stroke.Clinical trial registration: UMIN000020332.

Long-Term Safety and Efficacy of Durable Polymer Cobalt-Chromium Everolimus-Eluting Stents in Patients at High Bleeding Risk: A Patient-Level Stratified Analysis From Four Postapproval Studies.

BACKGROUND: Long-term outcomes in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention with a drug-eluting stent are unclear. Therefore, we aimed to evaluate long-term adverse events in HBR patients undergoing percutaneous coronary intervention with cobalt-chromium everolimus-eluting stent implantation. METHODS: We analyzed stratified data from 4 all-comers postapproval registries. Patients with at least 1 of the following criteria were categorized as HBR: age ≥75 years, history of major bleeding (MB), history of stroke, chronic oral anticoagulant use, chronic kidney disease, anemia, or thrombocytopenia. Additionally, in a separate analysis, patients were categorized according to the recently published Academic Research Consortium HBR criteria. The Kaplan-Meier method was used for time-to-event analyses. Coronary thrombotic events (CTE) included myocardial infarction or definite/probable stent thrombosis. MB was defined according to the TIMI (Thrombolysis in Myocardial Infarction) or GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) scales. Impact of CTE and MB on subsequent risk of mortality was assessed using multivariable Cox regression with MB and CTE included as time-updated covariates. RESULTS: Of the total 10 502 patients included, 3507 (33%) were identified as HBR. Compared with non-HBR patients, those at HBR had more comorbidities, higher lesion complexity, and a higher risk of 4-year mortality (Hazard Ratio [HR] 4.38 [95% CI, 3.76-5.11]). Results were qualitatively similar when using Academic Research Consortium criteria to define HBR. Risk of mortality was increased after CTE (HR 5.02 [95% CI, 3.93-6.41]), as well as after MB (HR 4.92 [95% CI, 3.82-6.35]). Of note, this effect was consistent across the spectrum of bleeding risk (P-interaction test 0.97 and 0.06, respectively). CONCLUSIONS: Compared with the non-HBR population, HBR patients experienced worse 4-year outcomes after percutaneous coronary intervention with cobalt-chromium everolimus-eluting stent. Both CTE and MB had a significant impact on subsequent risk of mortality irrespective of bleeding risk.

A novel I551F variant of the Na+/HCO3- cotransporter NBCe1-A shows reduced cell surface expression, resulting in diminished transport activity.

Homozygous mutations in SLC4A4, which encodes the electrogenic Na+/[Formula: see text] cotransporter (NBCe1), cause proximal renal tubular acidosis associated with extrarenal symptoms. Although 17` mutated sites in SLC4A4 have thus far been identified among patients with proximal renal tubular acidosis, the physiological significance of other nonsynonymous single-nucleotide variants (SNVs) remains largely undetermined. Here, we investigated the functional properties of SNVs in NBCe1. From the National Center for Biotechnology Information dbSNP database, we identified 13 SNVs that have not previously been characterized in the highly conserved, transmembrane domains of NBCe1-A. Immunocytochemical analysis revealed that the I551F variant was present predominantly in the cytoplasm in human embryonic kidney (HEK)-293 cells, whereas all other SNVs did not show as dramatic a change in subcellular distribution. Western blot analysis in HEK-293 cells demonstrated that the I551F variant showed impaired glycosylation and a 69% reduction in cell surface levels. To determine the role of I551 in more detail, we examined the significance of various artificial mutants in both nonpolarized HEK-293 cells and polarized Madin-Darby canine kidney cells, which indicated that only I551F substitution resulted in cytoplasmic retention. Moreover, functional analysis using Xenopus oocytes demonstrated that the I551F variant had a significantly reduced activity corresponding to 39% of that of the wild-type, whereas any other SNVs and artificial I551 mutants did not show significant changes in activity. Finally, immunofluorescence experiments in HEK-293 cells indicated that the I551F variant retained wild-type NBCe1-A in the cytoplasm. These data demonstrate that the I551F variant of NBCe1-A shows impaired transport activity predominantly through cytoplasmic retention and suggest that the variant can have a dominant negative effect by forming complexes with wild-type NBCe1-A.NEW & NOTEWORTHY Electrogenic Na+/[Formula: see text] cotransporter 1-A (NBCe1-A) in the proximal tubule regulates the acid/base balance and fluid volume homeostasis. From the National Center for Biotechnology Information dbSNP database, we identified the I551F variant of NBCe1-A, which showed reduced glycosylation, cell surface expression, and transport activity. We also found that the I551F variant can exert a dominant negative effect on wild-type NBCe1-A, suggesting its physiological significance.