Importance of B-Type Natriuretic Peptide in the Detection of Patients With Structural Heart Disease in a Primary Care Setting.

BACKGROUND: Early detection and intervention for preclinical heart failure (HF) are crucial for restraining the potential increase in patients with HF. Thus, we designed and conducted a single-center retrospective cohort study to confirm the efficacy of B-type natriuretic peptide (BNP) for the early detection of preclinical HF in a primary care setting.Methods and Results: We investigated 477 patients with no prior diagnosis of HF who were under the care of general practitioners. These patients were categorized into 4 groups based on BNP concentrations: Category 1, 0 pg/mL≤BNP≤35 pg/mL; Category 2, 35 pg/mL200 pg/mL. There was a marked and statistically significant increase in the prevalence of preclinical HF with increasing BNP categories: 19.9%, 57.9%, 87.5%, and 96.0% in Categories 1, 2, 3, and 4, respectively. Compared with Category 1, the odds ratio of preclinical HF in Categories 2, 3, and 4 was determined to be 5.56 (95% confidence interval [CI] 3.57-8.67), 23.70 (95% CI 8.91-63.11), and 171.77 (95% CI 10.31-2,861.93), respectively. CONCLUSIONS: Measuring BNP is a valuable tool for the early detection of preclinical HF in primary care settings. Proactive testing in patients at high risk of HF could play a crucial role in addressing the impending HF pandemic.

Rituximab in combination with cyclosporine and steroid pulse therapy for childhood-onset multidrug-resistant nephrotic syndrome: a multicenter single-arm clinical trial (JSKDC11 trial).

BACKGROUND: Only 80% of children with idiopathic nephrotic syndrome respond well to glucocorticoid therapy. Multidrug-resistant nephrotic syndrome (MRNS) is associated with a poor kidney prognosis. Several retrospective studies have identified rituximab as an effective treatment for MRNS; however, prospective studies are required to assess its efficacy and safety. METHODS: We conducted a multicenter, non-blinded, single-arm trial to investigate the efficacy and safety of rituximab in patients with childhood-onset MRNS who were resistant to cyclosporine and more than three courses of steroid pulse therapy. The enrolled patients received four 375 mg/m2 doses of rituximab in combination with baseline cyclosporine and steroid pulse therapy. The primary endpoint was a > 50% reduction in the urinary protein/creatinine ratio from baseline on day 169. Complete and partial remissions were also evaluated. RESULTS: Six patients with childhood-onset MRNS were enrolled. All patients were negative for pathogenic variants of podocyte-related genes. On day 169, five patients (83.3%) showed a > 50% reduction in the urinary protein/creatinine ratio, two patients showed partial remission, and two patients showed complete remission. No deaths occurred and severe adverse events occurred in two patients (infection in one patient and acute kidney injury in one patient). Three patients needed treatment for moderate-to-severe infection. CONCLUSIONS: The study treatment effectively reduced the urinary protein/creatinine ratio in patients with childhood-onset MRNS. The adverse events in this study were within the expected range; however, attention should be paid to the occurrence of infections.

Volume-outcome relationship in balloon aortic valvuloplasty: results of a consecutive, patient-level data analysis from a Japanese nationwide multicentre registry (J-SHD).

OBJECTIVE: Transcatheter balloon aortic valvuloplasty (BAV) remains an important alternative treatment for severe, symptomatic aortic stenosis. With increasing numbers of BAVs being performed, the need for large-scale volume-outcome relationship assessments has become evident. Here, we aimed to explain such relationships by analysing consecutive, patient-level BAV data recorded in a prospective Japanese nationwide multicentre registry. DESIGN: Prospective study. SETTING: Data of 1920 BAVs performed in 200 Japanese hospitals from January 2015 to December 2019. PARTICIPANTS: The mean patient age was 85 years, and 36.9% of procedures involved male patients. METHODS: The efficacy of BAV was assessed by reducing the mean transaortic valve gradient after the procedure. We also assessed in-hospital complication rates, including in-hospital death, bleeding, urgent surgery, distal embolism, vessel rupture and contrast-induced nephropathy. Based on the distribution of case volume (median 20, IQR 10-46), we divided the patients into high-volume (≥20) and low-volume (<20) groups. In-hospital complication risk was assessed with adjustment by logistic regression modelling. RESULTS: Indications for BAV included palliative/destination (44.2%), bridge to transcatheter aortic valve replacement (34.5%), bridge to surgical aortic valve replacement (7.4%) and salvage (9.7%). Reduction of the mean transaortic valve gradient was similar between the high-volume and low-volume groups (20 mm Hg vs 20 mm Hg, p=0.12). The proportion of in-hospital complications during BAV was 4.2%, and the incidence of complications showed no difference between the high-volume and low-volume groups (4.2% vs 4.1%, p=1.00). Rather than hospital volume, salvage procedure was an independent predictor of in-hospital complications (OR, 4.04; 95% CI, 2.03 to 8.06; p<0.001). CONCLUSION: The current study demonstrated that procedural outcomes of BAV were largely independent of its institutional volume.

Aetiology of chronic heart failure in patients from a super-aged society: the KUNIUMI registry chronic cohort.

AIMS: With the rapidly increasing ageing population, heart failure is an urgent challenge, particularly in developed countries. The study aimed to investigate the main aetiologies of chronic heart failure in a super-aged society. METHODS AND RESULTS: The KUNIUMI registry chronic cohort is a community-based, prospective, observational study of chronic heart failure in Awaji Island, Japan. Inhabitants of this island aged ≥65 years accounted for 36.3% of the population. In the present study, data from patients with symptomatic heart failure were extracted from the registry. A total of 1646 patients were enrolled from March 2019 to March 2021, accounting for ~1.3% of the inhabitants of Awaji Island. We analysed 852 patients with symptomatic heart failure. The mean age was high (78.7 ± 11.1 years), with 357 patients (41.9%) being female. The proportion of women increased significantly with advancing age and constituted more than half of the patients aged 85 years and older (P < 0.01). The prevalence of atrial fibrillation, and in particular long-standing persistent atrial fibrillation, increased at 70 years of age (P < 0.01). The proportion of patients with heart failure with preserved ejection fraction increased to ~60% when age was over 75 years. Although ischaemic heart disease accounted for 35.0% of chronic heart failure aetiologies, valvular heart disease was the most common cause of chronic heart failure (49.8%). The major types of valvular heart disease were mitral regurgitation and tricuspid regurgitation (27.2% and 21.7%, respectively), both of which increased significantly with age (P < 0.01). The incidence of aortic valve stenosis increased markedly over the age of 85 years (P < 0.01). Atrial functional mitral regurgitation increased with age and was the major cause of mitral regurgitation in patients aged >75 years. Patients with atrial functional mitral regurgitation had a higher prevalence of atrial fibrillation (especially long-standing persistent atrial fibrillation) and a larger left atrial volume index when compared with patients with other types of mitral regurgitation (P < 0.001, respectively). CONCLUSIONS: The KUNIUMI registry chronic cohort showed a change in heart failure aetiology to valvular heart disease in a super-aged society. Effective and comprehensive countermeasures are required to prepare for the rapid rise in heart failure incidence in a super-aged society.

Differences in Prognostic Factors among Patients Hospitalized for Heart Failure According to the Age Category: From the KUNIUMI Registry Acute Cohort.

Objective Previous studies have described several prognostic factors for heart failure (HF); however, these results were derived from registries consisting of conventional age groups, which might not represent the increasingly aging society. The present study explored the prognostic factors for all-cause death in hospitalized patients with HF across different age categories using an acute HF registry that included relatively old patients. Methods From a total of 1,971 consecutive patients with HF, 1,136 patients were enrolled. We divided the patients into 4 groups (≤65, 66-75, 76-85, and >85 years old) to evaluate all-cause death and prognostic factors of all-cause death. Results During the mean follow-up period of 1,038 days, 445 patients (39.2%) had all-cause death. A Kaplan-Meier analysis demonstrated significantly higher incidence of all-cause death in the elderly groups than in the younger groups (log-rank p<0.001). A Cox proportional-hazard regression analysis revealed that the presence of atrial fibrillation [hazard ratio (HR): 23.3, 95% confidence interval (CI): 2.36-231.1, p=0.007] was a notable predictive factor for all-cause death in the ≤65 years old group, whereas the Clinical Frailty Scale score (HR: 1.33, 95% CI: 1.16-1.52, p<0.001) and hypoalbuminemia (HR: 0.49, 95% CI: 0.31-0.78, p=0.003) were predictors in the >85 years old group. Conclusions Atrial fibrillation was a notable predictor of HF in young patients, whereas frailty and low-grade albuminemia were essential predictive factors of HF in elderly patients. With the increasing number of elderly patients with HF, comprehensive multidisciplinary treatment will be necessary.

Association of congestion with worsening renal function in acute decompensated heart failure according to age.

AIMS: Acute decompensated heart failure (ADHF) is a frequent cause of hospitalization for patients with heart disease, and ADHF patients are at high risk of heart failure (HF) re-hospitalization. Residual congestion at discharge is also a strong predictor of poor outcomes and re-hospitalization for ADHF patients. However, the impact of residual congestion at discharge on worsening renal function (WRF) in both high-aged and older patients remains uncertain because previous studies of WRF in ADHF patients were conducted for older patients. We therefore designed and conducted a retrospective, population-based study using the Kobe University Heart Failure Registry in Awaji Medical Center (KUNIUMI) Registry to investigate the association of residual congestion at discharge with WRF in ADHF patients according to age. METHODS AND RESULTS: We studied 966 hospitalized ADHF patients with a mean age of 80.2 ± 11.4 years from among 1971 listed in the KUNIUMI Registry. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level during the hospital stay compared with the value on admission. The primary endpoint was defined as cardiovascular death or HF re-hospitalization after discharge over a mean follow-up period of 2.0 ± 0.1 years. The primary endpoint was recorded for 369 patients (38.2%). As expected, patients with both WRF and residual congestion at discharge had significantly less favourable outcomes compared with those without one of them, and patients without either of these two characteristics had the most favourable outcomes, whereas those with residual congestion and with WRF had the least favourable outcomes. Moreover, WRF was significantly associated with worse outcomes for high-aged patients ≥80 years old, but not for those <80 years old if decongested. Multivariable Cox regression analysis showed that both residual congestion at discharge and WRF were the independent predictors of outcomes for high-aged patients, but residual congestion at discharge, not WRF, was the independent predictor of outcomes for older patients. CONCLUSIONS: Association of residual congestion at discharge with WRF for hospitalized ADHF patients can differ according to age. Our findings showed the importance of WRF and residual congestion at discharge for high-aged ADHF patients and of aggressive diuresis to alleviate congestion for older ADHF patients for better management of such patients in a rapidly ageing society.

Mycophenolate Mofetil after Rituximab for Childhood-Onset Complicated Frequently-Relapsing or Steroid-Dependent Nephrotic Syndrome.

BACKGROUND: Rituximab is the standard therapy for childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS after peripheral B cell recovery. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab). In total, 39 patients (per group) were treated with rituximab, followed by either MMF or placebo until day 505 (treatment period). The primary outcome was time to treatment failure (TTF) throughout the treatment and follow-up periods (until day 505 for the last enrolled patient). RESULTS: TTFs were clinically but not statistically significantly longer among patients given MMF after rituximab than among patients receiving rituximab monotherapy (median, 784.0 versus 472.5 days, hazard ratio [HR], 0.59; 95% confidence interval [95% CI], 0.34 to 1.05, log-rank test: P=0.07). Because most patients in the MMF group presented with treatment failure after MMF discontinuation, we performed a post-hoc analysis limited to the treatment period and found that MMF after rituximab prolonged the TTF and decreased the risk of treatment failure by 80% (HR, 0.20; 95% CI, 0.08 to 0.50). Moreover, MMF after rituximab reduced the relapse rate and daily steroid dose during the treatment period by 74% and 57%, respectively. The frequency and severity of adverse events were similar in both groups. CONCLUSIONS: Administration of MMF after rituximab may sufficiently prevent the development of treatment failure and is well tolerated, although the relapse-preventing effect disappears after MMF discontinuation.

Efficacy of Renin-angiotensin-aldosterone-system inhibitors for heart failure with preserved ejection fraction and left ventricular hypertrophy -from the KUNIUMI Registry Acute Cohort.

BACKGROUND: Heterogeneity of heart failure (HF) with preserved ejection fraction (HFpEF) would contribute to the difficulty in identifying effective treatments, and interest in the phenogrouping of HFpEF as a potential means for predicting patients who respond to cardioprotective drugs has been increasing. METHODS: We studied 468 first-hospitalized HFpEF patients among 1971 acute-hospitalized HF patients from KUNIUMI Registry Acute Cohort. The primary endpoint was defined as HF-rehospitalization and cardiovascular death over a median follow-up period of 508 days. RESULTS: In HFpEF patients with left ventricular hypertrophy (LVH), patients prescribed renin-angiotensin-aldosterone-system (RAAS) inhibitors had similar outcomes compared to those without (HR, 0.77; 95% CI 0.51-1.16; p = 0.21), and the outcome was also similar between patients with and without RAAS inhibitors' prescription in HFpEF patients without LVH. Moreover, in HFpEF patients with LVH and mild-moderate chronic kidney disease (CKD), which was determined as an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2, patients prescribed RAAS inhibitors had significantly favorable outcomes compared to those without (HR 0.39; 95% CI 0.19-0.80; p = 0.01). In HFpEF patients with LVH and severe CKD, which was defined as eGFR <30 mL/min/1.73 m2, the outcome was similar between patients with and without RAAS inhibitor prescription. Multivariable Cox regression analysis showed that the prescription of RAAS inhibitors was the only independent predictor of outcome in HFpEF patients with LVH and mild-moderate CKD (HR 0.49; 95% CI 0.25-0.94; p = 0.03). CONCLUSIONS: Our findings showed the importance of HFpEF phenogrouping for identifying effective pharmacological treatments.

Importance of Optimized Guideline-Based Therapy for Preventing Rehospitalization of Chronic Heart Failure Patients　- From the KUNIUMI Acute Cohort.

Background: Because the effectiveness of strengthening guideline-based therapy (GBT) to prevent heart failure (HF) rehospitalization of chronic HF patients remains unclear, this study investigated the characteristics of HF patients in the Kobe University Heart Failure Registry in Awaji Medical Center (KUNIUMI) acute cohort. Methods and Results: We studied 254 rehospitalized HF patients from the KUNIUMI Registry. Optimized GBT was defined as a Class I or IIa recommendation for chronic HF based on the guidelines of the Japanese Circulation Society. The primary endpoint was all-cause death or first HF rehospitalization after discharge. Outcomes tended to be more favorable for patients who had rather than had not received optimized GBT (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.57-1.19; P=0.27). Similarly, among New York Heart Association (NYHA) Class IV patients, outcomes tended to be more favorable for those who had rather than had not undergone optimized GBT (HR 0.73; 95% CI 0.47-1.12; P=0.15). Importantly, outcomes were significantly more favorable among NYHA Class IV patients aged <79 years who had rather than had not undergone optimized GBT (HR 0.33; 95% CI 0.14-0.82; P=0.02). Multivariate Cox regression analysis showed that optimized GBT was the only independent factor for the prediction of the primary endpoint. Conclusions: Optimized GBT can be expected to play an important role as the next move for chronic HF patients.

Estimating Incidence of Acute Heart Failure Syndromes in Japan　- An Analysis From the KUNIUMI Registry.

BACKGROUND: Few registries have provided precise information concerning incidence rates for acute heart failure syndrome (AHFS) in Japan.Methods and Results:All hospitals with acute care beds in Awaji Island participated in the Kobe University heart failure registry in Awaji Medical Center (KUNIUMI Registry), a retrospective, population-based AHFS registration study, enabling almost every patient with AHFS in Awaji Island to be registered. From 1 January 2015 to 31 December 2017, 743 patients with de novo AHFS had been registered. Mean age was 82.1±11.5 years. Using the general population of Japan as of 2015 as a standard, age- and sex-adjusted incidence rates for AHFS were 133.8 per 100,000 person-years for male and 120.0 for female. In 2015, there were an estimated 159,702 new-onset patients with AHFS, which was predicted to increase to 252,153 by 2040, and reach a plateau. The proportion of patients aged >85 years accounted for 42.6% in 2015, which was predicted to increase up to 62.5% in 2040. The proportion of patients with heart failure with preserved ejection fraction was estimated at 52.0% in 2015, which was predicted to increase gradually to 57.3% in 2055. CONCLUSIONS: The present analysis suggested that the number of patients with de novo AHFS keeps increasing with progressive aging in Japan. Establishment of countermeasures against the expanding burden of HF is urgently required.

The impact of vildagliptin on the daily glucose profile and coronary plaque stability in impaired glucose tolerance patients with coronary artery disease: VOGUE-A multicenter randomized controlled trial.

BACKGROUND: The impact of reduction in glycemic excursion on coronary plaques remains unknown. This study aimed to elucidate whether a dipeptidyl peptidase 4 inhibitor could reduce the glycemic excursion and stabilize the coronary plaques compared with conventional management in coronary artery disease (CAD) patients with impaired glucose tolerance (IGT). METHODS: This was a multicenter, randomized controlled trial including CAD patients with IGT under lipid-lowering therapy receiving either vildagliptin (50 mg once a day) or no medication (control group) regarding glycemic treatment. The primary endpoint was changes in the minimum fibrous cap thickness and lipid arc in non-significant native coronary plaques detected by optical coherence tomography at 6 months after intervention. Glycemic variability expressed as the mean amplitude of glycemic excursion (MAGE) measured with a continuous glucose monitoring system was evaluated before and 6 months after intervention. RESULTS: A total of 20 participants with 47 lesions were allocated to either the vildagliptin group (10 participants, 22 lesions) or the control group (10 participants, 25 lesions). The adjusted difference of mean changes between the groups was - 18.8 mg/dl (95% confidence interval, - 30.8 to - 6.8) (p = 0.0064) for the MAGE (vildagliptin, - 20.1 ± 18.0 mg/dl vs. control, 2.6 ± 12.7 mg/dl), - 22.8° (- 40.6° to - 5.1°) (p = 0.0012) for the mean lipid arc (vildagliptin, - 9.0° ± 25.5° vs. control, 15.8° ± 16.8°), and 42.7 µm (15.3 to 70.1 µm) (p = 0.0022) for the minimum fibrous cap thickness (vildagliptin, 35.7 ± 50.8 µm vs. control, - 15.1 ± 25.2 µm). CONCLUSIONS: Vildagliptin could reduce the MAGE at 6 months and may be associated with the decreased lipid arc and increased minimum FCT of the coronary plaques in CAD patients with IGT as compared with the control group. These findings may represent its potential stabilization effect on coronary plaques, which are characteristic in this patient subset. Trial registration Registered in the UMIN clinical trial registry (UMIN000008620), Name of the registry: VOGUE trial, Date of registration: Aug 6, 2012, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000010058.

Precipitating factors and clinical impact of early rehospitalization for heart failure in patients with heart failure in Awaji Island, Japan.

BACKGROUND: Recent reports have revealed that patients who experienced early rehospitalization for heart failure (HF) had worse prognoses in terms of all-cause and cardiovascular deaths as compared to those who did not. However, precipitating factors for early rehospitalization for HF remain unknown. In this study, we assessed the precipitating factors for early rehospitalization and their impact in patients with HF. METHODS AND RESULTS: We consecutively included 242 patients (mean age: 80.4 years, females: 46.3%) with a history of rehospitalization for HF. They were divided into 2 groups: the early rehospitalization group (71 patients who were readmitted within 3 months of discharge) and the late rehospitalization group (171 patients who were readmitted after more than 3 months following discharge). During the mean follow-up period of 1,144 days (range: 857-1,417 days), 121 patients (50.0%) died. Kaplan-Meier analysis revealed that patients in the early rehospitalization group had worse prognosis (all-cause death and cardiovascular death) than those in the late rehospitalization group (log-rank p<0.001). As the major precipitating factor for rehospitalization, poor compliance with the doctor's instructions on fluid and physical activity restrictions (determined by the patients or their families admittance of non-compliance with the instructions given at the time of discharge) was higher in the early rehospitalization group than in the late rehospitalization group [poor compliance with fluid restriction: 19.7% vs. 7.6% (p = 0.006), poor compliance with physical activity restriction: 21.1% vs. 9.4% (p = 0.013)]. CONCLUSIONS: We concluded that early hospital readmission in patients with HF was associated with higher mortality rates. Compared to late rehospitalization, precipitating factors for early rehospitalization were more strongly dependent on the self-care behaviors of the patients. A more effective approach, such as multidisciplinary intervention, is essential to prevent early hospital readmission and subsequent poor prognosis.

Efficacy of optical frequency domain imaging in detecting peripheral artery disease: the result of a multi-center, open-label, single-arm study.

Optical frequency domain imaging (OFDI) is a high-resolution intracoronary imaging modality with fast automated longitudinal pullback. We aimed to evaluate the ability of performing OFDI from the superficial femoral artery (SFA) to the below-knee (BK) artery. This clinical trial was a multi-center, single-arm, open-label study. The primary endpoint was to obtain a clear image of the intra-vascular lumen from the SFA to the BK artery, specifically > 270° visualization of the blood vessel lumen with > 16/21 cross sections. The proportion of the clear image (≥ 85%) was regarded as confirmatory of the ability of OFDI to visualize the vessel lumen. Overall, 20 patients were enrolled. The proportion of the primary endpoint was 90% (18/20), and the pre-specified criterion was successfully attained. The proportion of the clear image assessed by the operator was 100% (20/20), and an additional statistical analysis for the proportion of the visualization, > 270°, of the blood vessel lumen revealed a significantly higher cut-off value than that for the pre-specified criterion, 85% (p = 0.0315). There were three adverse events not related to OFDI. OFDI achieved acceptable visualization of the vessel lumen without any adverse event related to it. After regulatory approval based on the present study, OFDI will be available as a new option of endovascular imaging for peripheral artery diseases in daily practiceTrial registration: This study was registered in the Japanese Registry of Clinical Trials (jRCT 2052190025, https://jrct.niph.go.jp/latest-detail/jRCT2052190025 ).

Differences in clinical outcomes between pre- and post-marketing clinical study following paclitaxel-coated balloon catheter treatment for coronary in-stent restenosis: from the Japanese regulatory viewpoint.

In 2013, a drug-coated balloon catheter (DCB) (SeQuent Please) for the treatment of coronary in-stent restenosis (ISR) was approved in Japan. The pre-marketing Japan domestic NP001 study demonstrated better outcomes of the DCB (n = 138) compared to plain balloon angioplasty (n = 72). After the introduction to marketing, a post-marketing surveillance (PMS) (n = 396) was conducted to evaluate the safety and efficacy of the DCB in Japanese routine clinical practice. The aim of this paper was to assess differences between the pre-marketing NP001 study and the PMS. Compared to the NP001 study, more complex lesions were treated in the PMS (type B2/C: 69.0% vs 20.4%, total occlusion: 11.2% vs 0%, p < 0.001, respectively) and target lesion was more frequently ISR related to drug-eluting stent (DES) (79.5% vs 39.4%, p < 0.001). Regarding clinical outcomes, the rate of target lesion revascularization (TLR) was higher in the PMS than in the NP001 study (TLR: 12.9% at 7 months and 17.6% at 12 months vs 2.8% at 6 months, p = 0.001, p < 0.001, respectively). Multivariable logistic regression analysis revealed that DES-ISR was a risk factor of TLR after DCB treatment for ISR (odds ratio: 5.77, 95% CI 1.75-18.95, p = 0.004). Among representative published trials using DCB for ISR, clinical outcomes are often worse in DES-ISR trials than those in bare metal stent-ISR trials. The rates of TLR in previous DES-ISR trials are similar to that in the current PMS (TLR at 12 months: 22.1% for ISAR-DESIRE 3, 15.3% for PEPCAD-DES, and 13.0% for RIBS IV). The effectiveness and safety of DCB for coronary ISR have been confirmed in the Japanese real-world survey. PMS would be useful to evaluate the safety and effectiveness of medical products throughout their total life cycles.

Recent Least Burdensome Approach for the Approval of Innovative Medical Devices in Japan -Regulatory Approval Review of an Everolimus-eluting Bioresorbable Scaffold.

Although a domestic trial in Japan revealed that Absorb bioresorbable vascular scaffold (BVS) has no inferiority to everolimus-eluting stent (EES) cohort in the primary endpoint of the target lesion failure at 12 months, the scaffold/stent thrombosis (ST) rates with the BVS at 24 months were higher than those with the EES (Absorb BVS 3.1% vs. EES 1.5%), the ST rate of 3.1% with Absorb BVS is not an acceptable level in Japan. A cause-of-ST analysis revealed that cases in which diagnostic imaging and ensuing post-dilatation had been performed appropriately had lower ST rates than those without such management (within 1 year: 1.37% vs. 7.69%, from 1 to 2 years: 0.00% vs. 8.33%). Therefore, a further evaluation was needed to confirm that the ST rate with the Absorb BVS would be reduced by a proper implementation procedure. Regulatory approval was given conditionally to initiate rigorous post-marketing data collection in order to ensure the proper use of this device in limited facilities. The One-year Use-Result Survey in Japan for the Absorb BVS revealed no instances of ST. This approach to reducing the premarket regulatory burden of clinical trials and enhancing the post-marketing commitments of medical device regulation is useful for expediting patient access to innovative medical devices.

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.

Trial Design Principles for Patients at High Bleeding Risk Undergoing PCI: JACC Scientific Expert Panel.

Investigating the balance of risk for thrombotic and bleeding events after percutaneous coronary intervention (PCI) is especially relevant for patients at high bleeding risk (HBR). The Academic Research Consortium for HBR recently proposed a consensus definition in an effort to standardize the patient population included in HBR trials. The aim of this consensus-based document, the second initiative from the Academic Research Consortium for HBR, is to propose recommendations to guide the design of clinical trials of devices and drugs in HBR patients undergoing PCI. The authors discuss the designs of trials in HBR patients undergoing PCI and various aspects of trial design specific to HBR patients, including target populations, intervention and control groups, primary and secondary outcomes, and timing of endpoint reporting.

Correction to: Efficacy of optical frequency­domain imaging in detecting peripheral artery disease: a single­center open­label, single­arm study protocol.

In the original publication of the article, the author group was published without full names and one of the co-authors' name was published incorrectly. The full names of author group and correct co-authors' name are given in this Correction.

Independent Factors for In-Hospital Death Following Drug-Eluting Stent Thrombosis From the Japanese Adverse Event Report System.

BACKGROUND: Stent thrombosis (ST) is a serious complication after drug-eluting stents (DES) implantation. To identify the risk factors of mortality following ST, we evaluated adverse event reports used for safety measures after approval.Methods and Results:Between July 2004 and August 2019, 2,887 ST case reports were submitted to the Pharmaceutical and Medical Device Agency. Reports of probable or possible ST (n=604), with insufficient data regarding in-hospital outcome or duration between procedure and ST occurrence (n=37) or duplicate reports (n=191) were excluded. Accordingly, 2,045 reports with definite ST were analyzed. Among the subjects, there were 286 in-hospital deaths (14.0%). Multivariate logistic regression analysis revealed that left main trunk (LMT) (odds ratio [OR]: 4.76, 95% confidence interval [CI]: 3.26-6.96), chronic heart failure (CHF) (OR: 2.88, 95% CI: 1.61-5.14), hemodialysis (OR: 2.69, 95% CI: 1.66-4.36), prior stroke (OR: 2.28, 95% CI: 1.15-4.51), over 70 years old (OR: 1.62, 95% CI: 1.22-2.16), and right coronary artery (OR: 0.41, 95% CI: 0.27-0.63) were independent factors for in-hospital death after DES-ST. CONCLUSIONS: LMT, CHF, hemodialysis, prior stroke, and older age were independently associated with higher risk of in-hospital death following DES-ST. If target patients have these factors, maximum preventive strategies against ST occurrence, including adequate dual-antiplatelet therapy duration and optimal DES deployment procedures, are required.

The effect of multiple-inflation balloon aortic valvuloplasty.

Recent improvements of balloon aortic valvuloplasty (BAV) devices and procedures have provided improved outcomes, but it is not clear whether the multiple-inflation BAV technique is effective in patients with symptomatic severe aortic valve stenosis (AS). We conducted an analysis of the impact of multiple-inflation BAV (at least 6 times inflation) on the mean aortic valve area (AVA) and mean aortic valve pressure gradient (AV-PG) in patients with symptomatic severe aortic stenosis as compared with conventional BAV (from single to three times inflation). We identified two studies of multiple-inflation BAV with antegrade approach using Inoue-balloon catheter (425 patients) and four studies of conventional BAV (170 patients) with retrograde approach. Using a random intercept model, we found that multiple-inflation BAV significantly increased mean AVA (mean difference (MD) [95% indicates confidence interval (CI)] = 0.25 [0.16-0.34], P < 0.001) and significantly decreased mean AV-PG (MD [95% CI] = - 20.2 [- 27.8, - 12.70], P < 0.001) as compared with the conventional BAV. Furthermore, despite an extremely high Society of Thoracic Surgeons (STS) score (9.2-14.5), the all-cause mortality rate at one year of multiple-inflation BAV was 16-17%. The results of our analyses indicate that the multiple-inflation BAV technique seem to be effective for patients with symptomatic severe AS as compared with conventional BAV.