An Aspirin-Free Versus Dual Antiplatelet Strategy for Coronary Stenting: STOPDAPT-3 Randomized Trial.

BACKGROUND: Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials. METHODS: We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin. RESULTS: The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; Psuperiority=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; Pnoninferiority=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group. CONCLUSIONS: The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.

Aspirin versus Clopidogrel Monotherapy After Percutaneous Coronary Intervention: 1-Year Follow-up of the STOPDAPT-3 Trial.

BACKGROUND AND AIMS: There was no previous trial comparing aspirin monotherapy with a P2Y12 inhibitor monotherapy following short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: In the STOPDAPT-3, patients with acute coronary syndrome (ACS) or high bleeding risk (HBR) were randomly assigned to either 1-month DAPT with aspirin and prasugrel followed by aspirin monotherapy (aspirin group) or 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). This secondary analysis compared aspirin monotherapy with clopidogrel monotherapy by the 30-day landmark analysis. The co-primary endpoints were the cardiovascular endpoint defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischaemic stroke, and the bleeding endpoint defined as Bleeding Academic Research Consortium 3 or 5. RESULTS: Of 6002 assigned patients, 5833 patients (aspirin group: N = 2920 and clopidogrel group: N = 2913) were included in the 30-day landmark analysis. Median age was 73 (interquartile range 64-80) years, women 23.4%, ACS 74.6%, and HBR 54.1%. The assigned monotherapy was continued at 1 year in 87.5% and 87.2% in the aspirin and clopidogrel groups, respectively. The incidence rates beyond 30 days and up to 1 year were similar between the aspirin and clopidogrel groups for both cardiovascular endpoint (4.5 and 4.5 per 100 person-year, hazard ratio [HR] 1.00 [95% confidence interval (CI) 0.77-1.30], P = .97), and bleeding endpoint (2.0 and 1.9, HR 1.02 [95% CI 0.69-1.52], P = .92). CONCLUSIONS: Aspirin monotherapy compared to clopidogrel monotherapy was associated with similar cardiovascular and bleeding outcomes beyond 1 month and up to 1 year after PCI with DES.

Long-term effect of biodegradable vs durable polymer everolimus-eluting stents on neoatherosclerosis in ST-segment elevation myocardial infarction: the CONNECT trial.

BACKGROUND AND AIMS: Neoatherosclerosis is a leading cause of late (>1 year) stent failure following drug-eluting stent implantation. The role of biodegradable (BP) versus durable polymer (DP) drug-eluting stents on long-term occurrence of neoatherosclerosis remains unclear. Superiority of biodegradable against durable polymer current generation thin-strut everolimus-eluting stent (EES) was tested by assessing the frequency of neoatherosclerosis 3 years after primary percutaneous coronary intervention (pPCI) among patients with ST-segment elevation myocardial infarction (STEMI). METHODS: The randomized controlled, multicentre (Japan and Switzerland) CONNECT trial (NCT03440801) randomly (1:1) assigned 239 STEMI patients to pPCI with BP-EES or DP-EES. The primary endpoint was the frequency of neoatherosclerosis assessed by optical coherence tomography (OCT) at 3 years. Neoatherosclerosis was defined as fibroatheroma or fibrocalcific plaque or macrophage accumulation within the neointima. RESULTS: Among 239 STEMI patients randomized, 236 received pPCI with stent implantation (119 BP-EES; 117 DP-EES). A total of 178 patients (75%; 88 in the BP-EES group and 90 in the DP-EES group) underwent OCT assessment at 3 years. Neoatherosclerosis did not differ between the BP-EES (11.4%) and DP-EES (13.3%; odds ratio 0.83, 95% confidence interval 0.33-2.04, p=0.69). There were no differences in the frequency of fibroatheroma (BP-EES 9.1% vs DP-EES 11.1%, p=0.66) or macrophage accumulation (BP-EES 4.5% vs DP-EES 3.3%, p=0.68), and no fibrocalcific neoatherosclerosis was observed. Rates of target lesion failure did not differ between groups (BP-EES 5.9% vs DP-EES 6.0%, p=0.97). CONCLUSIONS: Use of BP-EES for primary PCI in patients presenting with STEMI was not superior to DP-EES regarding frequency of neoatherosclerosis at 3 years.

Impact of the clinical frailty scale on long-term outcomes after transcatheter aortic valve implantation.

BACKGROUND: The semiquantitative Clinical Frailty Scale (CFS) is reportedly a useful marker for predicting short- and mid-term mortality after transcatheter aortic valve implantation (TAVI). We assessed the long-term prognostic impact of CFS in patients with severe aortic stenosis undergoing TAVI. METHODS: We prospectively assessed patients undergoing TAVI in Kokura Memorial Hospital using a 9-level CFS and enrolled 1594 patients after excluding patients with CFS 8-9. The patients were divided into the low (CFS level, 1-3; N = 842), intermediate (4; N = 469), and high (5-7; N = 283) groups according to their CFS levels. RESULTS: In the low, intermediate, and high groups, 3-year all-cause mortality rates were 17.4%, 29.4%, and 41.7% (P < .001) and composite rates of cardiovascular mortality and heart failure hospitalization were 12.1%, 19.1%, and 23.9% (P < .001), respectively. Multivariable analysis showed that higher frailty was independently associated with all-cause mortality (intermediate group: adjusted hazard ratio [HR], 1.63, 95% confidence interval [CI], 1.24-2.15, P < .001; high group: adjusted HR, 2.18, 95% CI, 1.59-2.99, P < .001) and composite of cardiovascular mortality and heart failure hospitalization (intermediate group: adjusted HR, 1.47, 95% CI, 1.04-2.08, P = .030; high group: adjusted HR, 1.66, 95% CI, 1.09-2.51, P = .018) and this result was consistent, irrespective of stratification based on age, sex, body mass index, left ventricular ejection fraction, Society of Thoracic Surgeons score, and New York Heart Association functional class without significant interaction. CONCLUSIONS: The simple CFS tool predicts the long-term adverse outcomes post-TAVI.

Decremental properties of a concealed nodoventricular pathway.

INTRODUCTION: The decremental properties of the nodoventricular pathway (NVP) are uncertain. METHODS AND RESULTS: During short RP supraventricular tachycardia, a His-refractory premature ventricular contraction (PVC) consistently terminated the tachycardia without atrial capture immediately after the PVC. Whereas a slightly earlier PVC failed to reset the subsequent His but terminated the tachycardia without atrial capture one cycle later. CONCLUSION: These observations are diagnostic of slow-fast atrioventricular nodal reentrant tachycardia (AVNRT) with a bystander concealed-NVP and can be explained by decremental properties in the NVP itself; greater prematurity of the PVC resulted in more decremental conduction over the NVP, causing the AVNRT termination one cycle later.

Differential Prognostic Impact of Clinical Congestion between Preserved versus Reduced Ejection Fraction in Patients Hospitalized for Acute Decompensated Heart Failure: Findings from the Japanese Kyoto Congestive Heart Failure Registry.

BACKGROUND: Most patients hospitalized for heart failure (HF) present with signs of congestion. Prognostic significance of clinical congestion may vary depending on left ventricular ejection fraction (LVEF). This study aims to investigate the prognostic impact of congestion across different LVEF categories. METHODS AND RESULTS: Composite congestion scores (CCSs; 0-9) derived from the severity of edema, jugular venous pressure, and orthopnea, were analyzed on admission and at discharge in 3787 patients hospitalized for HF (LVEF ≥ 40%: n = 2347, LVEF < 40%: n = 1440). The median admission CCS was 4 in both LVEF strata (P = .64). Adjusted hazard ratios (HRs; 95% confidence interval [CI]) of the moderate (CCS 4-6) and severe congestion [7-9] groups relative to the mild congestion [0-3] group on admission for a composite of all-cause death or HF rehospitalization were 1.20 (1.04-1.39, P = .01) and 1.54 (1.27-1.86, P < .001) in the LVEF ≥ 40% stratum, and 1.20 (1.01-1.44, P = .04) and 0.82 (0.61-1.07, P = .14) in the LVEF < 40% stratum, respectively (Pinteraction< .001). A total of 16% of the patients with LVEF ≥40% and 14% with LVEF <40% had residual congestion (CCS ≥ 1) at discharge, which was associated with a respective adjusted HR of 1.40 (1.18-1.65, P < .001) and 1.25 (0.98-1.58, P = .07) for postdischarge death or HF rehospitalization (Pinteraction = 0.63). CONCLUSION: The severity of clinical congestion on admission was associated with adverse clinical outcomes in patients with LVEF ≥ 40%, but not in those with LVEF < 40%. These findings warrant further studies to better understand the detailed profile of congestion across the LVEF spectrum.

Impact of a Less Than 50% Residual Stenosis Following Vessel Preparation in Femoropopliteal Drug-Coated Balloon Angioplasty.

PURPOSE: Drug-coated balloon (DCB) has been established as first-line therapy in femoropopliteal (FP) intervention, and successful vessel preparation (VP) is considered a key element. However, the clinical impact of successful VP remains unknown. This retrospective study examined the clinical impact of successful VP in DCB FP intervention. METHODS: In total, 268 patients (308 limbs) who underwent successful FP intervention using DCB without atherectomy devices for symptomatic lower extremity artery disease between March 2018 and December 2019 were included in this study (high-dose DCB: 69.8%; low-dose DCB: 30.2%). Successful VP was defined as <50% residual stenosis and

High-Dose Drug-Coated Balloon Versus Polymer-Based Drug-Eluting Stent for Femoropopliteal Artery Disease Treatment.

PURPOSE: Clinical trials have demonstrated that high-dose drug-coated balloon (HD-DCB) and polymer-based drug-eluting stent (PB-DES) treatments for femoropopliteal (FP) artery disease have favorable outcomes. However, which one would be better remained unrevealed. METHODS: This study used the databases of 2 large-scale multicenter prospective drug-coated balloon (DCB) and drug-eluting stent (DES) registries. The study included 2470 patients with symptomatic FP lesion treated with IN.PACT Admiral DCB or Eluvia DES at 69 centers. A propensity-score-based paired analysis was conducted. Primary endpoint was 1-year restenosis rate. Secondary endpoints were 1-year reocclusion rate, target lesion revascularization (TLR), acute thrombosis, bypass conversion, major amputation, major adverse limb event (MALE), and all-cause death. RESULTS: A total of 1535 patients were treated with HD-DCB, and 935 patients were treated with PB-DES. The propensity-score matching extracted 678 pairs, with no remarkable intergroup difference in baseline characteristics. The 1-year restenosis rate was significantly lower in the PB-DES group than in the HD-DCB group (16.0% vs 22.0%, p=0.016). The other endpoints (reocclusion rate, TLR, acute thrombosis, bypass conversion, major amputation, MALE, and all-cause death) did not differ between the groups. No baseline characteristics had any significant interaction effect on the association of HD-DCB vs PB-DES with restenosis risk (all p>0.05). CONCLUSIONS: This study demonstrated that the 1-year TLR, reocclusion rate, and other endpoints did not differ between the PB-DES group and the HD-DCB group despite the lower restenosis in the PB-DES group. CLINICAL IMPACT: One-year restenosis rate was significantly lower in the polymer-based DES group than in the high-dose DCB group for foemoropopliteal disease. However, there is no difference in the other endpoints between two groups.

Impact of High Lipoprotein(a) Levels on Delayed Wound Healing in Patients With Chronic Limb-Threatening Ischemia After Peripheral Endovascular Therapy.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] levels are a causal risk factor for peripheral artery disease. However, data on their effect on delayed wound healing in patients with chronic limb-threatening ischemia (CLTI) are limited. The present study assessed the association between elevated Lp(a) levels and delayed wound healing in patients with CLTI. METHODS AND RESULTS: This study included 280 patients who successfully received endovascular therapy for CLTI between September 2016 and August 2021. High Lp(a) levels were defined as those >30 mg/dL. The primary outcome was wound healing. During a median follow-up of 20.4 months (interquartile range 6.8-38.6 months), 146 patients achieved wound healing. The wound healing rate at 24 months was significantly lower in the high Lp(a) than low Lp(a) group (41.1% vs. 86.3%, respectively; P<0.001). The adjusted risk ratio was 0.19 (95% confidence interval 0.13-0.29, P<0.001). Lp(a) levels of 31-50 and >50 mg/dL, but not 16-30 mg/dL, were significantly associated with delayed wound healing relative to Lp(a) levels of ≤15 mg/dL. CONCLUSIONS: Elevated Lp(a) levels were independently associated with delayed wound healing in patients with CLTI treated with endovascular therapy.

Long-Term Effects of Proton Pump Inhibitors in Patients Undergoing Percutaneous Coronary Intervention in High-Risk Subgroups.

BACKGROUND: Proton pump inhibitors (PPIs) reportedly reduce upper gastrointestinal bleeding (UGIB) in patients undergoing percutaneous coronary intervention (PCI). However, whether the benefits of PPIs differ in high-risk subgroups is unknown. METHODS AND RESULTS: Among 24,563 patients undergoing first PCI in the CREDO-Kyoto registry Cohort-2 and -3, we evaluated long-term effects of PPI for UGIB, defined as GUSTO moderate/severe bleeding, in several potential high-risk subgroups. In the study population, 45.6% of patients were prescribed PPIs. Over a median 5.6-year follow-up, PPIs were associated with lower adjusted risk of UGIB (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.50-0.80; P<0.001) and a non-significant but numerically lower risk of any gastrointestinal bleeding (HR 0.84; 95% CI 0.71-1.01; P=0.06). PPIs were not associated with a lower risk of GUSTO moderate/severe bleeding (HR 1.04; 95% CI 0.94-1.15; P=0.40) or a higher adjusted risk of myocardial infarction or ischemic stroke (HR 1.00; 95% CI 0.90-1.12; P=0.97), but were associated with higher adjusted mortality risk (HR 1.18; 95% CI 1.09-1.27; P<0.001). The effects of PPIs for UGIB, myocardial infarction or ischemic stroke, and all-cause death were consistent regardless of age, sex, acute coronary syndrome, high bleeding risk, oral anticoagulant use, and type of P2Y12inhibitor. CONCLUSIONS: PPIs were associated with a lower risk of UGIB and a neutral risk of ischemic events regardless of high-risk subgroup.

Concomitant Mitral Regurgitation in Severe Aortic Stenosis　- Insights From the CURRENT AS Registry-2.

BACKGROUND: Data on concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) are scarce.Methods and Results: We investigated the risk of concomitant MR in patients with severe AS in the CURRENT AS Registry-2 according to initial treatment strategy (transcatheter aortic valve implantation [TAVI], surgical aortic valve replacement [SAVR], or conservative). Among 3,365 patients with severe AS, 384 (11.4%) had moderate/severe MR (TAVI: n=126/1,148; SAVR: n=68/591; conservative: n=190/1,626). The cumulative 3-year incidence for death or heart failure (HF) hospitalization was significantly higher in the moderate/severe than no/mild MR group in the entire population (54.6% vs. 34.3%, respectively; P<0.001) and for each treatment strategy (TAVI: 45.0% vs. 31.8% [P=0.006]; SAVR: 31.9% vs. 18.7% [P<0.001]; conservative: 67.8% vs. 41.6% [P<0.001]). The higher adjusted risk of moderate/severe MR relative to no/mild MR for death or HF hospitalization was not significant in the entire population (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.95-1.39; P=0.15); however, the risk was significant in the SAVR (HR 1.92; 95% CI 1.04-3.56; P=0.04) and conservative (HR 1.30; 95% CI 1.02-1.67; P=0.04) groups, but not in the TAVI group (HR 1.03; 95% CI 0.70-1.52; P=0.86), despite no significant interaction (Pinteraction=0.37). CONCLUSIONS: Moderate/severe MR was associated with a higher risk for death or HF hospitalization in the initial SAVR and conservative strategies, while the association was less pronounced in the initial TAVI strategy.

Difference in one-year late lumen loss between high- and low-dose paclitaxel-coated balloons for femoropopliteal disease.

The objective of the study is to investigate the difference in 1-year late lumen loss (LLL) between the high- (IN.PACT Admiral) and low-dose (Lutonix) paclitaxel-coated balloon (PCB). Although a recent randomized clinical trial demonstrated no difference in efficacy endpoint between high- and low-dose PCB, it remains unclear whether high-dose PCB was superior to low-dose PCB in actual clinical practice. We enrolled 64 patients with 67 de novo femoropopliteal lesions who underwent PCB angioplasty at Kokura Memorial Hospital from May 2014 to March 2020 and subsequent follow-up angiography after 1 year. The primary endpoint was 1-year LLL, whereas the secondary endpoints were binary restenosis and clinically driven target lesion revascularization (CD-TLR) after 1 year. The high- and low-dose PCB groups had 45 and 22 lesions, respectively. Although the low-dose PCB group had higher rates of coronary artery disease, hemodialysis, and chronic limb-threatening ischemia than the high-dose PCB group, the latter had a longer lesion length and more lesions with a TASC classification C or D than the former. The high-dose PCB group had a significantly lower LLL than the low-dose PCB group (0.40 ± 1.05 vs. 1.19 ± 1.03 mm; P = 0.003, respectively). Moreover, the high-dose PCB group had significantly lower rates of binary restenosis at 1 year than the low-dose PCB group (22.2% vs. 50.0%; P = 0.02, respectively). Moreover, negative LLL was only observed in the high-dose PCB group (33.3% vs. 0%, P = 0.005). The high-dose PCB group had a significantly lower LLL than the low-dose PCB group.

Assessment of Antitachycardia Pacing in Primary Prevention Patients: The APPRAISE ATP Randomized Clinical Trial.

Importance: The emergence of novel programming guidelines that reduce premature and inappropriate therapies along with the availability of new implantable cardioverter-defibrillator (ICD) technologies lacking traditional endocardial antitachycardia pacing (ATP) capabilities requires the reevaluation of ATP as a first strategy in terminating fast ventricular tachycardias (VTs) in primary prevention ICD recipients. Objective: To assess the role of ATP in terminating fast VTs in primary prevention ICD recipients with contemporary programming. Design, Setting, and Participants: This global, prospective, double-blind, randomized clinical trial had an equivalence design with a relative margin of 35%. Superiority tests were performed at interim analyses and the final analysis if equivalence was not proven. Patients were enrolled between September 2016 and April 2021 at 134 sites in 8 countries, with the last date of follow-up on July 6, 2023. Patients were required to have an indication for a primary prevention ICD, including left ventricular ejection fraction less than or equal to 35%. Interventions: Patients were randomized in a 1:1 ratio to receive ATP plus shock vs shock only. Main Outcomes and Measures: The primary end point was time to first all-cause shock. Secondary end points included time to first appropriate shock, time to first inappropriate shock, all-cause mortality, and the composite of time to first all-cause shock plus all-cause mortality. Results: A total of 2595 patients were randomized (mean age, 63.9 years; 22.4% were females). At a mean follow-up of 38 months, first all-cause shock occurred in 129 participants in the ATP plus shock group and 178 participants in the shock only group. The hazard ratio (HR) for the primary end point was 0.72 (95.9% CI, 0.57-0.92), with P = .005 for superiority of the ATP plus shock group over the shock only group. During follow-up in an intention-to-treat analysis, the total shock burden per 100 patient-years was not statistically different, at 12.3 and 14.9, respectively (P = .70). Conclusions and Relevance: The use of a single burst of ATP prior to shock in primary prevention ICD recipients with modern ICD detection programming prolonged the time to first all-cause ICD shock. Trial Registration: ClinicalTrials.gov Identifier: NCT02923726.

A novel ablation strategy for recurrent atrial fibrillation: Fractionated signal area in the atrial muscle ablation 1-year follow-up.

INTRODUCTION: Treatment of recurrent atrial fibrillation (AF) is sometimes challenging due to non-pulmonary vein (PV) foci. Fractionated signal area in the atrial muscle (FAAM) is a valid predictor of the location of non-PV foci. FAAM ablation has the potential to decrease the recurrence rate of atrial tachyarrhythmia in patients with recurrent AF. We compared the clinical impact of FAAM ablation for recurrent AF, using 1 year follow up date. METHODS: A total of 230 consecutive patients with symptomatic recurrent AF who underwent catheter ablation specifically targeting non-PV foci as FAAM-guided ablation (n = 113) and non-FAAM-guided ablation (n = 117) were retrospectively analyzed. FAAM was assigned a parameter (peaks slider, which indicates the number of components of fractionated signals), ranging from 1 to 15, indicating the location of the FAAM (1: largest, 15: smallest). FAAM-guided ablation was performed by ablating FAAM until none inducibility of non-PV foci. On the other hand, non-FAAM-guided ablation was performed via linear ablation, complex fractionated atrial electrogram ablation, superior vena cava isolation, and focal ablation according to the location of the non-PV foci. The RHYTHMIA system was used to perform all the procedures. The primary endpoints were AF recurrence, atrial flutter, and/or atrial tachycardia. RESULTS: After a 1-year follow up, freedom from atrial tachyarrhythmia was achieved in 90.3% and 75.2% of patients in the FAAM and non-FAAM groups, respectively (hazard ratio = 0.438 [95% confidence interval: 0.243-0.788], p = .005). CONCLUSIONS: FAAM ablation showed a promising decrease in the recurrence rate of atrial tachyarrhythmia in patients with recurrent AF during a 1-year follow-up.

Prognostic Value of the Severity of Clinical Congestion in Patients Hospitalized for Decompensated Heart Failure: Findings From the Japanese KCHF Registry.

BACKGROUND: Congestion is a leading cause of hospitalization and a major therapeutic target in patients with heart failure (HF). Clinical practice in Japan is characterized by a long hospital stay, which facilitates more extensive decongestion during hospitalization. We herein examined the time course and prognostic impact of clinical congestion in a large contemporary Japanese cohort of HF. METHODS AND RESULTS: Peripheral edema, jugular venous pressure, and orthopnea were graded on a standardized 4-point scale (0-3) in 3787 hospitalized patients in a Japanese cohort of HF. Composite Congestion Scores (CCS) on admission and at discharge were calculated by summing individual scores. The primary outcome was a composite of all-cause death or HF hospitalization. The median admission CCS was 4 (interquartile range, 3-6). Overall, 255 patients died during the median hospitalization length of 16 days, and 1395 died or were hospitalized for HF over a median postdischarge follow-up of 396 days. The cumulative 1-year incidence of the primary outcome increased at higher tertiles of congestion on admission (32.5%, 39.3%, and 41.0% in the mild [CCS ≤3], moderate [CCS = 4 or 5], and severe [CCS ≥6] congestion groups, respectively, log-rank P < .001). The adjusted hazard ratios of moderate and severe congestion relative to mild congestion were 1.205 (95% confidence interval [CI], 1.065-1.365; P = .003) and 1.247 (95% CI, 1.103-1.410; P < .001), respectively. Among 3445 patients discharged alive, 85% had CCS of 0 (complete decongestion) and 15% had a CCS of 1 or more (residual congestion) at discharge. Although residual congestion predicted a risk of postdischarge death or HF hospitalization (adjusted hazard ratio, 1.314 [1.145-1.509]; P < .001), the admission CCS correlated with the risk of postdischarge death or HF hospitalization, even in the complete decongestion group. No correlation was observed for postdischarge death or HF hospitalization between residual congestion at discharge and admission CCS (P for the interaction = .316). CONCLUSIONS: In total, 85% of patients were discharged with complete decongestion in Japanese clinical practice. Clinical congestion, on admission and at discharge, was of prognostic value. The severity of congestion on admission was predictive of adverse outcomes, even in the absence of residual congestion. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017241 (UMIN000015238).

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.

Effect of High-Dose Drug-Coated Balloon Repetition After Drug-Coated Balloon Failure.

PURPOSE: Although the optimal treatment for femoropopliteal (FP) drug-coated balloon (DCB) restenosis lesions remains debatable, the effectiveness of DCB repetition for DCB restenosis has been reported. However, the optimal DCB repetition strategy is not yet established. Thus, this study aimed to compare the clinical outcomes of high-dose DCB repetition with those of low-dose DCB repetition for FP DCB restenosis lesions. MATERIALS AND METHODS: This single-center, observational study used a clinical database of 677 consecutive patients undergoing FP endovascular intervention for symptomatic peripheral artery disease between December 2018 and December 2021. Of these patients, 89 cases treated with DCB repetition for FP DCB restenosis lesions were analyzed. The primary endpoint was recurrent restenosis (re-restenosis) and the secondary endpoints were recurrent target-lesion revascularization (TLR), re-occlusion, and major adverse limb events (MALE) obtained using propensity score matching. Interaction analysis was also performed to explore the effects of the baseline characteristics on the association between high- and low-dose DCB with restenosis risk. RESULTS: After propensity score matching, high-dose DCB demonstrated a significantly higher freedom from re-restenosis compared with low-dose DCB repetition at 1 year (90.4% vs 40.9%, p=0.034). In addition, freedom from re-TLR and MALE at 1 year was significantly higher in the high-dose DCB group (95.0% vs 53.3%, p=0.025; 95.0% vs 54.7%, p=0.025, respectively). Conversely, freedom rates from re-occlusion were not significantly different between the 2 groups (100.0% vs 84.0%, p=0.99). No baseline characteristics or perioperative outcomes had any significant interaction effect on the association of high-dose DCB versus low-dose DCB with restenosis risk. CONCLUSION: For FP DCB restenosis lesions, high-dose DCB repetition offered more favorable outcomes than low-dose DCB repetition. CLINICAL IMPACT: This study revealed that for femoropopliteal drug-coated balloon (DCB) restenosis lesions, high-dose DCB repetition obtained more favorable outcomes than low-dose DCB repetition. In addition, there was no significant interaction effect on the association of high- versus low-dose DCB with re-restenosis risk for the baseline characteristics and perioperative outcomes. This finding might be also a reason for choosing high-dose DCB repetition for FP DCB restenosis lesions in daily clinical practice.

Zero-Contrast Left Atrial Appendage Closure in Patients With Chronic Kidney Disease.

BACKGROUND: Left atrial appendage closure (LAAC) usually requires contrast medium during the procedure. However, patients with chronic kidney disease (CKD) are at high risk of developing contrast nephropathy. This study aimed to assess the safety and feasibility of zero-contrast LAAC in patients with CKD.Methods and Results: Zero-contrast LAAC was attempted in 15 patients with CKD Stages 3b-5 who were not on hemodialysis. All procedures were performed successfully, without any periprocedural complications. At the 45-day follow-up, no device-related complications or acute kidney disease were observed. CONCLUSIONS: The strategy of zero-contrast LAAC in patients with CKD can be an acceptable option.

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.

Safety and Performance of the Micra VR Leadless Pacemaker in a Japanese Cohort　- Comparison With Global Studies.

BACKGROUND: The Micra leadless pacemaker has demonstrated favorable outcomes in global trials, but its real-world performance and safety in a Japan-specific population is unknown.Methods and Results: Micra Acute Performance (MAP) Japan enrolled 300 patients undergoing Micra VR leadless pacemaker implantation in 15 centers. The primary endpoint was the acute (30-day) major complication rate. The 30-day and 6-month major complication rates were compared to global Micra studies. All patients underwent successful implantation with an average follow-up of 7.23±2.83 months. Compared with previous Micra studies, Japanese patients were older, smaller, more frequently female, and had a higher pericardial effusion risk score. 11 acute major complications were reported in 10 patients for an acute complication rate of 3.33% (95% confidence interval: 1.61-6.04%), which was in line with global Micra trials. Pericardial effusion occurred in 4 patients (1.33%; 3 major, 1 minor). No procedure or device-related deaths occurred. Frailty significantly improved from baseline to follow-up as assessed by Japan Cardiovascular Health Study criteria. CONCLUSIONS: In a Japanese cohort, implantation of the Micra leadless pacemaker had a high success rate and low major complication rate. Despite the Japan cohort being older, smaller, and at higher risk, the safety and performance was in line with global Micra trials.