Edoxaban vs. Vitamin K Antagonist for Atrial Fibrillation After Transcatheter Aortic Valve Replacement in Japanese Patients　- A Subanalysis of the ENVISAGE-TAVI AF Trial.

BACKGROUND: Japanese patients undergoing transcatheter aortic valve replacement (TAVR) are often female and have a small body size, potentially impacting bleeding risk with antithrombotic therapy. Outcomes of direct oral anticoagulant use in these patients with atrial fibrillation (AF) need to be clarified.Methods and Results: This prespecified analysis included Japanese patients from ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial that compared treatment with edoxaban and vitamin K antagonists (VKAs) in patients with AF after TAVR. The primary efficacy and safety outcomes were net adverse clinical events (NACE; composite of all-cause death, myocardial infarction, ischemic stroke, systemic embolic event, valve thrombosis, and International Society on Thrombosis and Haemostasis [ISTH]-defined major bleeding) and ISTH-defined major bleeding, respectively. Intention-to-treat (ITT) and on-treatment analyses were performed. Overall, 159 Japanese patients were enrolled (edoxaban group: 82, VKA group: 77) and followed for on average 483 days. Mean patient age was 83.8 years; 52.2% were female. In the ITT analysis, NACE rates were 10.9%/year with edoxaban and 12.5%/year with VKA (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.38-1.90); major bleeding occurred in 8.9%/year and 7.3%/year, respectively (HR, 1.17; 95% CI, 0.45-3.05). In edoxaban- and VKA-treated patients, rates of ischemic stroke were 1.8%/year and 1.0%/year, respectively; fatal bleeding rates were 0.9%/year and 2.0 %/year. On-treatment results were similar to ITT. CONCLUSIONS: In Japanese patients with AF after successful TAVR, edoxaban and VKA treatment have similar safety and efficacy profiles.

Long-term results of primary stenting for subclavian artery disease.

OBJECTIVES: To evaluate initial and long-term results of endovascular therapy (EVT) for symptomatic subclavian artery (SCA) disease. BACKGROUND: EVT for SCA disease has a similar success rate as open surgery, but the long-term patency of EVT alone is uncertain. METHODS: We retrospectively studied 59 consecutive patients (42 males and 17 females) with 60 lesions. Mean patient age was 68 ± 10 years. Clinical symptoms were vertebrobasilar insufficiency in 21 patients (35.0%), arm claudication in 20 patients (33.3%), angina pectoris in 12 patients (20%), severe arm ischemia in 3 patients (5.0%), vascular access insufficiency in 3 patients (5.0%), and leg ischemia in 1 patient (1.7%). A total of 57 stents were implanted. All patients were followed up at 1, 3, 6, and 12 months after the procedure and annually thereafter. RESULTS: The technical success rate was 93.3%. All patients for whom technical success was obtained received stents. There were four technical failures, all of which were owing to the failure of crossing the wire in occluded lesions. There were no procedure-related deaths. There were two stroke events (3.4%) and one embolic event (1.7%). Primary patency rates were 94.9, 90.8, and 85.8% at 1, 3, and 5 years, respectively. CONCLUSIONS: EVT for SCA disease is an effective treatment with regard to initial success rate, clinical efficacy, and long-term primary patency. This minimally invasive procedure is appropriate as the treatment of first choice for proximal subclavian arterial obstructive disease.

Impact of changing PSVR thresholds on the patency rates of SFA recanalisation with self-expanding nitinol stents.

AIMS: The primary patency of superficial femoral artery (SFA) stents is evaluated by measuring PSVR. However, each trial uses a different definition of PSVR. We investigated the impact of changing PSVR thresholds on the patency rates of SFA recanalisation with self-expanding nitinol stents. METHODS AND RESULTS: A single-centre retrospective study was conducted. Between 2003 and 2006, 76 consecutive patients (83 limbs) were treated using nitinol self-expanding stents for SFA disease. Primary patency was defined as categories 1 (PSVR <2.0), 2 (PSVR <2.4) and 3 (PSVR <2.85). The mean follow-up time was 51±27 months. For one, five, and seven years, Kaplan-Meier estimates for primary patency rates were 62.6%, 36.8%, and 27.6%, respectively, in category 1; 75.2%, 46.5%, and 37.1%, respectively, in 2; and 75.2%, 46.1%, and 46.1%, respectively, in 3. The primary patency between categories 1 and 3 (p=0.038) was significantly different. No difference was observed between categories 2 and 3 (p=0.786), and a trend for differences was observed between categories 1 and 2 (p=0.069). CONCLUSIONS: PSVR definition may influence the reported long-term patency rate of a SFA stent. We should consider the definition of restenosis in each trial.

Cardiac benefits of renal artery stenting.

AIMS: The aims of this study were to evaluate the effects of renal stenting on cardiac function using echocardiographic parameters, and to clarify whether changes in clinical and echocardiographic variables after renal stenting differ between atherosclerotic renal artery stenosis (ARAS) patients with and without cardiac symptoms. METHODS AND RESULTS: A total of 61 patients who underwent renal stenting and echocardiography were included in the study. Left ventricular (LV) filling pressure and LV relaxation were evaluated with tissue Doppler imaging. The ratio of the peak early diastolic mitral inflow velocity to the peak early mitral annular velocity (E/e' ratio) and the e'-velocity were measured to assess diastolic function. LV ejection fraction remained unchanged, but the E/e' ratio (P<0.001) and the e'-velocity (P=0.004) improved after renal stenting. In particular, the E/e' ratio improved from 13.7±5.6 to 11.9±4.0 (P=0.002) within 24 hours after renal stenting and remained low at 11.2±3.8 after a mean follow-up period of 7±4 months (P=0.001). Patients with cardiac symptoms showed significantly better change in E/e' ratio (P=0.002) and E-velocity (P=0.005) compared to those without cardiac symptoms. Cardiac symptoms also significantly improved after renal stenting (New York Heart Association functional class: 2.5±0.6 at baseline to 1.4±0.6 at follow-up; P<0.001). CONCLUSIONS: Renal stenting improved echocardiographic parameters that reflect LV diastolic function, and yielded a higher benefit for E/e' ratio and E-velocity in patients with cardiac symptoms than in those without cardiac symptoms.

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

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

Renal artery stenosis in cardio-and cerebrovascular disease: renal duplex ultrasonography as an initial screening examination.

BACKGROUND: The prevalence and indicative clinical factors of renal artery stenosis (RAS) in the Japanese population are unclear. METHODS AND RESULTS: The aim of this study was to investigate the prevalence of RAS in a selectively referred Japanese population and to determine any clinical factors related to RAS by initially screening with renal duplex ultrasonography. The 750 patients presenting because of possible or known cardio-and cerebrovascular diseases were prospectively studied. Duplex examination was performed in 729 patients (97.2%): 21 patients (2.8%) did not undergo it, because of technical impossibility. Duplex RAS was found in 38 patients (5.2%). Subsequently, a confirmatory renal angiography was obtained in 40 patients, investigating those who had duplex RAS or no duplex examination. Angiographic RAS was found in 35 patients (4.8%). The respective prevalences of duplex and angiographic RAS were 6.3% and 6.7% in coronary artery disease, 8.8% and 9.3% in multivessel coronary artery disease, 7.5% and 8.2% in heart failure, 5.1% and 4.3% in unstable angina pectoris, 20.0% and 22.2% in carotid artery stenosis, 10.3% and 10.2% in stroke, 20.0% and 20.0% in peripheral artery disease, and 12.0% and 11.8% in abdominal aortic aneurysm. Univariate analysis showed that patients with duplex RAS were older and had more atherosclerotic risk factors. Furthermore, they were more likely to be smokers and have hypertension, renal impairment, renal atrophy, left ventricular hypertrophy and cardio- and cerebrovascular diseases. Multivariate stepwise analysis showed that smoking, peripheral artery disease, abdominal aortic aneurysm and renal atrophy were independent predictors of duplex RAS. CONCLUSIONS: RAS is frequent in Japanese patients with cardio- and cerebrovascular diseases. Initial screening for RAS by duplex ultrasonography is recommended for patients with complications, especially peripheral artery disease, abdominal aortic aneurysm and renal atrophy.

Double-wire technique in balloon-protected carotid artery stenting.

OBJECTIVES: To evaluate the safety and efficacy of a double-wire technique in carotid artery stenting (CAS) with a distal occlusion balloon system, PercuSurge GuardWire. METHODS: Fifty-one consecutive patients with 53 de novo lesions were scheduled to undergo balloon-protected CAS with the "double-wire technique," the use of two wires, one for independent predilatation and the other for stent implantation. RESULTS: Fifty consecutive patients underwent a total of 52 balloon-protected CAS except for 1 patient with one lesion that could not be accessed. The use of a 1.5-mm coronary balloon was necessary in only 2 cases (3.8%) to let the PercuSurge GuardWire cross critically stenotic lesions. The placement of the PercuSurge GuardWire into the internal carotid artery was successful in all cases. Technical success was obtained in all cases. Fifty lesions (96.2%) were treated with one inflation of the distal occlusion balloon during the entire procedure consisting of predilatation, stent implantation, and aspiration, and among them three lesions (5.8%) required postdilatation. The mean occlusion time of cerebral blood flow for 50 lesions was 266 +/- 37 seconds. Out of 50 procedures, 45 (90.0%) had occlusion times of 300 seconds or less. Neurological intolerance requiring intravenous anesthesia was seen in 4 cases (7.7%) and periprocedural neurological complication in 2 cases (3.8%). CONCLUSIONS: The "double-wire technique" is safe and effective for the shortening of occlusion time during predilatation, stent implantation, and aspiration, leading to satisfactory technical and clinical outcomes, in most cases. This technique should be considered for balloon-protected CAS using the PercuSurge GuardWire.

Transradial intervention for native fistula failure.

The native radiocephalic (Brescia-Cimino) fistula is usually constructed with an anastomosis of the cephalic vein and radial artery. Catheter interventions for native fistula failure have until now been performed via the transcephalic or transbrachial approach. Transradial intervention for native fistula failure was prospectively evaluated for a selected consecutive 11 patients. Six patients had a single lesion and 5 patients had double lesions. Twelve lesions were stenotic and 4 were occlusive with thrombus. Balloon angioplasty alone was successful in 10 lesions. In thrombosed fistulas, 2 lesions underwent manual catheter-directed thrombo-aspiration and 2 further lesions underwent a combination of catheter-directed thrombo-aspiration and mechanical thrombectomy. Cutting Balloon angioplasty was performed for 3 resistant venous stenoses and for 1 radial artery stenosis. Technical and clinical success were achieved in all patients. No vessel rupture or perforation was observed in this study, nor was distal embolization in the radial artery or symptomatic pulmonary embolism. No radial artery occlusion or fistula infection was seen during the follow-up. The primary patency rates were 82% at 3 months and 64% at 6 months. Transradial intervention for native fistula failure is considered safe and feasible in a selected population; yet requires further validation.

The performance of renal duplex ultrasonography for the detection of hemodynamically significant renal artery stenosis.

OBJECTIVES: The value of renal duplex ultrasonography for the detection of angiographical renal artery stenosis (RAS) has been demonstrated in many clinical studies. None of the published studies, however, have adequately scrutinized the performance of this modality for the detection of hemodynamically significant RAS. The purpose of this study is to investigate the correlation and accuracy between renal duplex parameters and translesional pressure gradient (TLPG). METHODS: A total of 60 patients, with 75 stenotic lesions in the renal arteries determined by angiography, underwent duplex ultrasonography before angiography and the measurement of TLPG using a 0.014'' pressure wire in the single setting of angiography were prospectively included. Peak systolic velocity (PSV) in the renal artery and a ratio of PSV in the renal artery to the aorta (RAR) were examined as duplex ultrasonography parameters. Angiographical stenosis was evaluated by percent diameter stenosis (%DS) derived from quantitative angiographic analysis. RESULTS: The correlation with TLPG proved to be stronger in the following order, PSV (r = 0.743, P < 0.001), %DS (r = 0.701, P < 0.001), and RAR (r = 0.572, P < 0.001). The best performing parameter for TLPG of 20 mm Hg was revealed to be PSV, as the areas under the receiver operator characteristics curves using %DS, PSV, and RAR were 0.888, 0.939, and 0.834, respectively. A PSV cutoff value of 219 cm/sec provided the best predictive value with a sensitivity of 89%, a specificity of 89%, and an accuracy of 89%. The positive predictive value was 83% and the negative predictive value was 93%. CONCLUSIONS: The measurement of PSV is not only noninvasive but also highly accurate in detecting patients who have hemodynamically significant RAS. The authors emphasize that an enthusiastic application of renal duplex ultrasonography, particularly the measurement of PSV, is warranted.

Chronic total occlusions in the superficial femoral artery: a novel strategy using a 1.5 mm J-tip hydrophilic guidewire with an over-the-wire balloon catheter under ultrasound guidance.

Chronic total occlusions in the superficial femoral artery (SFA) are the longest and straightest lesions in the whole body. This presents additional technical challenges and the inability to cross the occluded lesion is a common cause of procedural failure in these percutaneous interventions. The objective of this study was to investigate the usefulness of a strategy using a hydrophilic 1.5 mm J-tip 0.035'' guidewire with an over-the-wire balloon catheter under ultrasound guidance for chronic total occlusions in the SFA. This strategy was performed in 32 consecutive patients (36 limbs). Average occlusion length was 17 +/- 10 cm (3-40 cm). The crossover approach was performed in 26 cases (72%); in the remaining 10 cases, the antegrade ipsilateral approach was selected. The technical success rate was 92% (32/36). A secondary popliteal artery approach was performed in the three failed limbs and was successful in two limbs, increasing the final technical success rate to 97%. This novel procedure may be considered the preferred strategy for intervening in chronic total occlusions in the SFA.

Carotid stenosis and peripheral artery disease in Japanese patients with coronary artery disease undergoing coronary artery bypass grafting.

The combination of a change in lifestyle toward Western habits and an aging society, has led to a steady increase in the incidence of atherosclerotic diseases in the Japanese population. Coronary artery disease (CAD), carotid stenosis (CS), and peripheral artery disease (PAD) are major manifestations of generalized atherosclerosis and increase the risk of cardiovascular events. However, the incidence of CS and PAD in Japanese patients with CAD is not well known, so the present study investigated this in 380 consecutive patients with CAD undergoing elective coronary aorta bypass grafting (CABG) at Kishiwada Tokushukai Hospital between October 1999 and October 2001. The coexistence of CS and PAD in all patients was preoperatively evaluated by duplex ultrasonography and the ankle - brachial index (ABI). The average age of the study population was 66.09.1 years (range, 42-87). The number of male patients was 293 (77.1%). The incidence of CS was 13.7% and 15.3% for PAD. Multivariate logistic regression analysis demonstrated that no particular traditional atherosclerotic risk factor, such as hypertension, hyperlipidemia, diabetes mellitus, and smoking, was able to predict either CS or PAD, but CS and PAD were independent predictors of each other. The results of the study suggest that CS and PAD were not only highly prevalent but also strongly associated with each other in this cohort of CAD patients. Accordingly, extracoronary atherosclerotic disease should be assessed in Japanese CAD patients.