Ultrasound-guided stenting in the common femoral vein for accurate stent distal landing.

Objective/Background: Venous stenting has been reported with excellent clinical results; however, inadequate inflow can increase the risk of stent occlusion. When extending the stent into the common femoral vein (CFV), it is essential to ensure adequate inflow from the femoral vein, deep femoral vein (DFV), and great saphenous vein. Accurate identification of the distal landing zone (DLZ) of the stent is crucial to ensure adequate inflow. The DLZ is usually determined by venography or intravascular ultrasound (IVUS) with reference to bony landmarks. However, the uncertainty can lead to misidentification of the DLZ and inadequate stent placement, resulting in stent occlusion. Methods: From December 2016 to December 2022, 42 venous stent placements were performed in 40 patients with post-thrombotic iliofemoral vein obstruction and/or stenosis. Three patients had developed early stent occlusion owing to a misidentified DLZ. To improve accuracy in identifying the DLZ during venous stenting, ultrasound-guided placement was performed in the CFV of five patients (four on the left and one on the right) with post-thrombotic changes in the CFV and occlusion of the common iliac vein and external iliac vein. The distal end of the stent was adjusted just above the saphenofemoral junction in two cases and just proximal to the DFV confluence in three cases. Stent placement was verified using both long-axis ultrasound and fluoroscopy. Results: Ultrasound images of the CFV region provided clear visualization of the stent deployment site and accurate landmark locations, such as the saphenofemoral junction and DFV confluence, allowing for precise adjustments during stent deployment. This technique enabled easier and more definitive identification of other branches of the CFV than previously provided by IVUS and venography. No complications were observed in any of the 42 cases, and long-term patency was achieved at the final follow-up after stenting (average, 10 months; range, 3-14 months). Conclusions: Ultrasound-guided stenting in the CFV allows for real-time and accurate stent deployment with precise adjustment to the optimal DLZ. Using this technique, combined with venography and IVUS, missed distal lesions and subsequent stent occlusion can be prevented, potentially contributing to better treatment outcomes.

Angioscopic evaluation after venous stents.

BACKGROUND: Venous stenting is increasingly used to manage femoro-ilio-caval venous outflow obstruction/stenosis due to post-thrombotic syndrome. Although the safety, efficacy, and long-term patency of venous stents have been reported, re-interventions due to stent occlusion and in-stent restenosis (ISR) have also been reported. The mechanism of ISR and the in-stent neointimal growth after venous stenting remains unclear. We performed angioscopy to evaluate intraluminal details after venous stenting, allowing real-time direct visualization of the vessel lumen. METHODS: Ten angioscopic procedures in four patients with post-thrombotic syndrome were performed. All evaluated vessels were stented iliac veins, and their native pathology was chronic post-thrombotic occlusion. Nine procedures in three patients underwent serial evaluation of the neointimal changes after stent implantation to study the natural time course of neointimal proliferation/coverage over the stent. The serial follow-up angioscopic evaluations were performed at the end of the venous stent deployment procedure, and at 6 months, 12 months, and 24 months. One procedure was performed 1 month after the stent implantation to evaluate ISR, which was observed at the first month of routine stent surveillance. A 5.7F angioscope was used to visualize the target veins. Continuous irrigation was used to displace blood and clear the visual field. RESULTS: At 6 months after stent implantation, stent struts were covered by a thin neointima in two of the three patients. The struts were partially covered in one patient, but there was little neointimal growth overall. Neointimal coverage increased over time, and at 12 months stent struts in 2 patients were almost completely covered. There was no significant change between the 12 and 24 months after stent implantation. In the ISR case, angioscopy demonstrated an overgrown thickened neointima, and the stent struts were fully embedded and invisible in the entire stented area. No thrombus and no webs or trabeculae were found in the area evaluated as an ISR lesion. CONCLUSIONS: At 6 months after stent placement, the stent struts were almost covered by a neointima. The stent struts were completely covered 1 year after stent implantation. Neointimal coverage was unchanged from the 1-year follow-up to the 2-year follow-up, suggesting that neointimal proliferation proceeded gradually with subsequent neointimal remodeling up to 1 year. The cause of ISR might be the overgrown thickened neointima rather than the formation of thrombosis.

Correlation between "Nutcracker phenomenon" and venous hypertension of the lower extremities: Three case reports.

We report three cases of left renal vein (LRV) compression resulting in deep venous insufficiency of the lower extremities, among which two patients showed clinical symptoms in both lower extremities. All patients were treated successfully with LRV stenting. The pathophysiology suggested that the secondary gonadal vein reflux owing to LRV compression drained into the iliac veins, resulting in a volume overload and venous hypertension in the iliocaval region. Computed tomography angiography was useful in diagnosing this condition, allowing the evaluation of LRV compression, identification of early opacification of the gonadal vein reflux, and exclusion of other pathologies resulting in deep venous insufficiency of the lower extremities.

Post-thrombotic syndrome of the lower extremity associated with arteriovenous fistula: Three case reports.

The post-thrombotic syndrome is a serious complication of deep vein thrombosis. Post-thrombotic iliac venous occlusion (PTIVO) is rarely associated with an arteriovenous fistula (AVF); however, the underlying mechanism remains unclear. We reported three PTIVO cases associated with an AVF, two symptomatic cases treated with venous stenting, and one asymptomatic case followed up conservatively. The essential imaging findings to diagnose PTIVO with an AVF were the presence of an arterial waveform on ultrasound examination and early opacification on contrast-enhanced computed tomography in the iliofemoral veins. Venous stenting resulted in the disappearance of the AVF, drastic improvement in symptoms, and an excellent long-term outcome.

Determinants of Drug-Coated Balloon Failure in Patients Undergoing Femoropopliteal Arterial Intervention.

BACKGROUND: Drug-coated balloons (DCB) are frequently used to treat femoropopliteal artery disease. However, patency loss occurs in ≥10% of patients within 12 months posttreatment with poor understanding of the underlying mechanisms. OBJECTIVES: The authors sought to investigate the determinants of DCB failure in femoropopliteal disease. METHODS: Data from randomized clinical trials (IN.PACT SFA, MDT-2113 SFA Japan) and 2 prespecified imaging cohorts of the IN.PACT Global Clinical Study were included. Influential procedural characteristics were evaluated by an independent angiographic core laboratory. The primary endpoint was DCB failure (patency loss during follow-up). Additional endpoints were binary restenosis and clinically driven target lesion revascularization. Multivariable analyses evaluated the clinical, anatomical, and procedural predictors of DCB failure. RESULTS: Included were 557 participants with single lesions and 12-month core laboratory-adjudicated duplex ultrasonography. Key clinical characteristics were as follows: mean age 68.8 years, 67.5% male, 87.6% with hypertension, 76.9% with hyperlipidemia, 40.5% with diabetes mellitus, 90.5% in Rutherford Classification Category (RCC) 2 to 3, and 9.5% in RCC 4 to 5. Average length and reference vessel diameter (RVD) were 16.37 cm and 4.66 mm, respectively; 49.7% of lesions were totally occluded. In multivariable analysis, only residual stenosis >30% was associated with patency loss, whereas residual stenosis >30% and smaller preprocedure RVD were associated with increased binary restenosis risk. RCC >3 and residual stenosis >30% were associated with increased 12-month clinically driven target lesion revascularization risk. CONCLUSIONS: Patency loss after DCB treatment was influenced by procedural and clinical factors. Residual stenosis >30%, smaller preprocedure RVD, and higher RCC may be considered predictors of increased risk of DCB failure and its components in femoropopliteal artery disease. (Randomized Trial of IN.PACT Admiral® Drug Coated Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [INPACT SFA I]; NCT01175850; IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA] [INPACT SFA II]; NCT01566461; MDT-2113 Drug-Eluting Balloon vs. Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery [MDT-2113 SFA]; NCT01947478; IN.PACT Global Clinical Study; NCT01609296).

Clinical Characteristics and Outcomes of Patients Presenting With Acute Myocardial Infarction Without Cardiogenic Shock.

BACKGROUND: Most patients with acute myocardial infarction (AMI) present in the emergency department in a hemodynamically stable condition (i.e., non-cardiogenic shock) (AMI-NCS). However, few studies specifically focused on the clinical characteristics and outcomes of AMI-NCS patients. Temporal trends in clinical characteristics, in-hospital occurrence of in-hospital adverse outcomes, and the effect of primary percutaneous coronary intervention (PPCI) were examined.Methods and Results: Between April 2012 and March 2018, 176,275 AMI-NCS patients (67.7% of the total AMI population; 25.4% female; mean age 68.6±13.1 years) were identified in a nationwide Japanese administrative database. During the 6-year study period, AMI-NCS patients have been getting older and had an increasing burden of comorbidities. The rates of 30-day all-cause mortality and in-hospital complications were 2.6% and 30.5%, respectively. Thirty-day all-cause mortality did not change significantly over time, whereas in-hospital complications, especially major non-cardiac events, increased progressively. On multivariable analyses, higher age, higher Killip class, atrial fibrillation, chronic renal failure, and malignancy were independently associated with both increased 30-day mortality and in-hospital complications. PPCI was independently associated with lower mortality and in-hospital complications. CONCLUSIONS: The clinical background of AMI-NCS patients has been becoming more complex with increasing age and the burden of comorbidities, with increased in-hospital complications. More active and appropriate application of PPCI may further decrease adverse events and improve survival of AMI-NCS patients.

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.

Independent Predictors of Major Adverse Cardiovascular Events at 3 Years after Aortoiliac Stent Implantation.

PURPOSE: To identify the risk factors for major adverse cardiovascular events (MACEs) in real-world practice for symptomatic peripheral artery disease in Japan. MATERIALS AND METHODS: Data on Japanese patients (N = 880) from the Observational Prospective Multicenter Registry Study on Outcomes of Peripheral Arterial Disease Patients Treated by Angioplasty Therapy for Aortoiliac Artery who underwent de novo aortoiliac stent placement. The 3-year risk of incident MACEs was investigated. RESULTS: The median age of the patients was 72.6 years (range, 34-97 years), and 83.1% of the patients were men. The patients had the following conditions: smoking (35.6%), hypertension (94.1%), dyslipidemia (81.7%), diabetes (48.0%), renal failure on dialysis (12.6%), myocardial infarction (12.7%), stroke (15.8%), and chronic limb-threatening ischemia (7.1%). Femoropopliteal lesions were present in 38.8% of the limbs with aortoiliac lesions. The 3-year rate of freedom from MACEs was 89.1%. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, were independently associated with the risk of incident MACEs. When the study population was stratified according to these risk factors, the rate of MACEs was highest in patients with at least 3 risk factors (32.9% at 3 years). CONCLUSIONS: The 3-year rate of freedom from MACEs was reported. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, are independent risk factors for MACEs after aortoiliac stent placement.

Long-term results of the Japanese multicenter Viabahn trial of heparin bonded endovascular stent grafts for long and complex lesions in the superficial femoral artery.

OBJECTIVE: We assessed the long-term safety and efficacy of endovascular stent grafting to treat long, complex lesions in the superficial femoral artery (SFA). METHODS: The present prospective, multicenter study at 15 Japanese hospitals assessed heparin-bonded stent grafts used to treat long SFA lesions in patients with symptomatic peripheral arterial disease. The inclusion criteria were Rutherford category 2 to 5 symptoms (grade 5 without active infection), an ankle brachial index of ≤0.9, and SFA lesions ≥10 cm long with ≥50% stenosis. The key efficacy and safety outcomes were primary-assisted patency and adverse events through 24 months, respectively. The secondary outcomes included primary patency, secondary patency, freedom from target lesion revascularization (fTLR), and Vascular Quality of Life questionnaire score. RESULTS: Of the 103 patients (mean age, 74.2 ± 7.0 years; 82.5% male), 100 (97.1%) had intermittent claudication. The average lesion length was 21.8 ± 5.8 cm; 87 lesions (84.5%) were TASC (Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease) C or D (65.7% chronic total occlusions). Of the 103 patients, 92 and 61 were evaluable through 24 and 60 months, respectively. At 24 months, the Kaplan-Meier-estimated primary-assisted patency, primary patency, and secondary patency rate was 85.7% (95% confidence interval [CI], 76.3%-91.5%), 78.8% (95% CI, 68.8%-85.9%), and 92.0% (95% CI, 82.4%-96.5%), respectively. The mean ankle brachial index was 0.64 ± 0.12 at baseline and 0.94 ± 0.19 at 24 months (P < .0001). At 24 and 60 months, the fTLR was 87.2% (95% CI, 78.9%-92.3%) and 79.1% (95% CI, 67.9%-86.8%), respectively. No device- or procedure-related life- or limb-threatening critical events or acute limb ischemia cases were observed through 5 years. No stent fractures were detected on the annually scheduled follow-up radiographs. The vascular quality of life questionnaire and walking impairment questionnaire scores were significantly increased at 1 through 24 months compared with the baseline scores (P < .0001 for both). One patient had required conversion to open bypass during the 5-year follow-up period. CONCLUSIONS: Stent grafting of long and complex SFA lesions in patients with claudication is safe and effective through long-term follow-up, with 79.1% fTLR and no leg amputation, acute limb ischemia, or stent fractures through 5 years.

A Multicenter Prospective Observational Cohort Study to Investigate the Effectiveness and Safety of Rivaroxaban in Japanese Venous Thromboembolism Patients (The J'xactly Study).

BACKGROUND: There is insufficient real-world data on the current status of Japanese patients with venous thromboembolism (VTE) or its treatment and prevention with rivaroxaban.Methods and Results:In this multicenter, prospective, observational study conducted in Japan, 1,039 patients with acute symptomatic/asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) with or without DVT prescribed rivaroxaban were enrolled at 152 institutions and observed for a median of 21.3 months. Mean age was 68.0±14.7 years, mean body weight was 60.3±14.1 kg, 59.0% were females, and 19.0% had active cancer. Incidences of recurrence or aggravation of symptomatic VTE (primary effectiveness outcome) and major bleeding (principal safety outcome) were 2.6% and 2.9% per patient-year, respectively. These outcomes did not differ between patients with DVT and those with PE (primary effectiveness outcome: 2.6% vs. 2.5% per patient-year, P=0.810; principal safety outcome: 3.5% vs. 2.4% per patient-year, P=0.394). The incidence of composite clinically relevant events, including recurrence or aggravation of symptomatic VTE, acute coronary syndrome, ischemic stroke, all-cause death, or major bleeding events, was 9.2% per patient-year. Multivariate analysis revealed that male sex, being underweight, having active cancer, chronic heart and lung disease, and previous stroke were independent determinants for composite clinically relevant events. CONCLUSIONS: In Japanese clinical practice, a single-drug approach with rivaroxaban was demonstrated to be a valuable treatment for a broad range of VTE patients.

Prasugrel effectively reduces the platelet reactivity units in patients with genetically metabolic dysfunction of cytochrome P450 2C19 who are treated with long-term dual antiplatelet therapy after undergoing drug-eluting stent implantation.

Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitor is administered following percutaneous coronary intervention (PCI) with coronary stent implantation. Several studies have reported the effects of switching between P2Y12 inhibitors on platelet reactivity (P2Y12 reaction units: PRU), from acute to late phase after PCI. However, the effect of switching at very late phase is unknown. This study examined the effect on PRU in Japanese coronary heart disease patients with long-term DAPT (aspirin + clopidogrel) when switching from clopidogrel to prasugrel. Ninety-six patients were enrolled in this study. The median DAPT duration at enrollment was 1824.0 days. Twenty-three patients with PRU ≥ 208 at enrollment were randomly assigned into either continuing to receive clopidogrel (Continued Group; n = 11) or switching to prasugrel (Switched Group; n = 12). The primary endpoint was the rate of patients who achieved PRU < 208 at the end of 12 weeks of treatment, which was significantly higher in Switched Group relative to Continued Group (90.0% vs. 36.4%; P = 0.024). The secondary endpoint was the PRU at week 12 in groups subdivided according to cytochrome P450 (CYP) 2C19 genotypes. At week 12, extensive metabolizers (EM Group) had 202.3 ± 60.0 and 174.5 ± 22.3 in Continued Group and Switched Group (P = 0.591), respectively; intermediate and poor metabolizers (non-EM Group) had 229.4 ± 36.9 and 148.4 ± 48.4 in Continued Group and Switched Group (P = 0.002), respectively. The PRU for non-EM Group was significantly reduced in Switched Group. Thus, for patients with long-term DAPT (aspirin + clopidogrel) after PCI with coronary stent implantation, switching from clopidogrel to prasugrel resulted in a stable reduction in PRU, regardless of CYP2C19 polymorphism.

Prognostic Implication of Functional Incomplete Revascularization and Residual Functional SYNTAX Score in Patients With Coronary Artery Disease.

OBJECTIVES: The aim of this study was to investigate the prognostic implication of functional incomplete revascularization (IR) and residual functional SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (rFSS) in comparison with 3-vessel fractional flow reserve (FFR) and residual SYNTAX score. BACKGROUND: IR is associated with poor clinical outcomes in patients who underwent percutaneous coronary intervention. METHODS: A total of 385 patients who underwent 3-vessel FFR measurement after stent implantation were included in this study. The rFSS was defined as residual SYNTAX score measured only in vessels with FFR ≤0.8. The study population was divided into the functional IR group (rFSS ≥1) and the functional complete revascularization (CR) group (rFSS = 0). The primary outcome was major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization) at 2 years. RESULTS: Functional CR was achieved in 283 patients (73.5%). At 2-year follow-up, the functional IR group showed a significantly higher risk for MACEs (functional IR vs. CR, 14.6% vs. 4.2%; hazard ratio: 4.09; 95% confidence interval: 1.82 to 9.21; p < 0.001) than the functional CR group. In a multivariate-adjusted model, functional IR was an independent predictor of MACEs (adjusted hazard ratio: 4.17; 95% confidence interval: 1.85 to 9.44; p < 0.001). The rFSS showed a significant association with estimated 2-year MACE rate (hazard ratio: 1.09 per 1-U increase; 95% confidence interval: 1.02 to 1.17; p = 0.018). When added to clinical risk factors, rFSS showed the highest integrated discrimination improvement value for MACEs (3.5%; p = 0.002) among 3-vessel FFR, residual SYNTAX score, and rFSS. CONCLUSIONS: Patients with functional IR showed significantly higher rate of 2-year MACEs than those with functional CR. A combined anatomic and physiological scoring system (rFSS) after stent implantation better discriminated the risk for adverse events than anatomic or physiological assessment alone. (Clinical Implication of 3-Vessel Fractional Flow Reserve [FFR]; NCT01621438).

Outcomes of the Japanese multicenter Viabahn trial of endovascular stent grafting for superficial femoral artery lesions.

OBJECTIVE: The objective of this study was to assess 1-year safety, efficacy, and invasiveness outcomes of endovascular stent grafting of symptomatic long lesions (≥10 cm) in the superficial femoral artery (SFA) as a substitute for above-knee open bypass surgery. METHODS: This prospective, multicenter (15 hospitals) study assessed heparin-coated stent grafts for the treatment of long SFA lesions in Japanese subjects with peripheral arterial disease. Inclusion criteria were Rutherford category 2 to 5 symptoms (grade 5 without active infection), ankle-brachial index ≤0.9, and color flow duplex ultrasound-assessed SFA lesions with cumulative length ≥10 cm and ≥50% stenosis. Main efficacy and safety outcomes were primary assisted patency and adverse events, respectively. Secondary outcomes included primary patency using the surgical bypass definition, that is, blood flow through a device without requiring target lesion revascularization (TLR) to maintain or to restore flow. For comparison with prior endovascular studies, primary patency-interventional was defined as peak systolic velocity ratio <2.5 without TLR in treated lesions. Other outcomes included freedom from TLR and Vascular Quality of Life questionnaire scoring. General anesthesia avoidance and hospitalization duration were compared with historical data from 68 consecutive patients (n = 51 Rutherford 2/3 claudicants and 17 Rutherford 4/5 subjects) who underwent above-knee bypass surgery at study sites between 2002 and 2012 and met study enrollment criteria. RESULTS: Of 103 enrollees (74.2 ± 7.0 years old; 17.5% female; 97.1% claudicants), 100 subjects were evaluated through postoperative 12 months. Average lesion length was 21.8 ± 5.8 cm, and 65.7% were totally occluded. The whole-cohort Kaplan-Meier estimated primary assisted patency rate was 94.1% (95% confidence interval [CI], 87.3%-97.3%) at 12 months. The primary patency-surgical rate was 92.1% (95% CI, 84.8%-96.0%), the primary patency-interventional rate was 88.1% (95% CI, 80.0%-93.1%), and freedom from TLR was 93.1% (95% CI, 86.1%-96.7%). Mean ankle-brachial index increased from 0.64 ± 0.12 to 0.98 ± 0.12 at 1 month after intervention and 0.94 ± 0 .17 at 12 months (P < .0001 at both follow-ups). Target vessel revascularization, major amputation, or death did not occur through postoperative 30 days. No life- or limb-threatening intraoperative or perioperative adverse events and no acute limb ischemia cases were observed during follow-up. Vascular Quality of Life questionnaire score increased from 58.6% ± 15.7% to 72.9% ± 18.6% at 12 months (P < .0001). No stent fractures were detected. No stent graft participant required general anesthesia, and median postoperative hospital stay was 2.0 days (mean, 3.4 ± 2.9 days) in the Viabahn (W. L. Gore & Associates, Flagstaff, Ariz) claudicant subgroup, values that were significantly lower than the 76.5% general anesthesia rate (P < .0001) and 11.0 days median hospitalization stay (mean, 12.7 ± 5.3 days; P < .0001) in the 51 open bypass claudicant subjects. CONCLUSIONS: Stent grafting appears to be a safe and less invasive alternative to above-knee bypass surgery, providing 88% to 92% primary patency at 12 months in long, complex lesions.

Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI.

BACKGROUND: Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. METHODS: We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. RESULTS: At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, -0.2 percentage points; 95% confidence interval [CI], -2.3 to 1.8; P<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P=0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients [3.1%] vs. 385 patients [30.8%], P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P=0.001). CONCLUSIONS: Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. (Funded by Philips Volcano; DEFINE-FLAIR ClinicalTrials.gov number, NCT02053038 .).

Drug-eluting stenting for femoropopliteal lesions, followed by cilostazol treatment, reduces stent restenosis in patients with symptomatic peripheral artery disease.

BACKGROUND: Cilostazol improves clinical endovascular therapy outcomes for femoropopliteal (FP) lesions in patients with symptomatic peripheral arterial disease, but whether it also has clinical benefits for patients after drug-eluting stent implantation remains unclear. METHODS: This study is a subanalysis of the ZilvEr PTX for tHe Femoral ArterY and Proximal Popliteal ArteRy (ZEPHYR) study, a prospective multicenter study investigating FP lesions treated with the Zilver (Cook Medical, Bloomington, Ind) paclitaxel-eluting stent. The present study analyzed 475 lesions in 459 limbs of 399 patients who maintained therapy with aspirin and thienopyridine, with or without cilostazol, during the 1-year follow-up period. RESULTS: Restenosis rates at 1 year were assessed with duplex ultrasound imaging (peak systolic velocity ratio >2.4) or angiography (≥50% diameter stenosis) and compared in the groups with and without cilostazol. Propensity score matching was performed to minimize intergroup differences in baseline characteristics. The present study included 93 cilostazol-treated and 382 cilostazol-free cases. Among the patients, 71% had diabetes mellitus and 31% were on dialysis. Critical limb ischemia accounted for 29% of cases. The prevalence of de novo lesions was 76%, and in-stent restenosis was present in 15%. Propensity score matching was performed in 91 pairs. The 1-year restenosis rate was 33% (95% confidence interval [CI], 23%-43%) in the cilostazol-treated group and 51% (95% CI, 41%-62%) in the cilostazol-free group (P = .008). The odds ratio was 0.5 (95% CI, 0.3-0.8). CONCLUSIONS: The propensity score-matching analysis demonstrated that additional cilostazol administration was associated with a significantly lower restenosis incidence 1 year after drug-eluting stent implantation for FP lesions.

Incidence and its characteristics of repetition of reintervention after drug-eluting stent implantation for femoropopliteal lesion.

OBJECTIVE: Although clinical trials demonstrated the superiority of the Zilver (Cook Medical, Bloomington, Ind) paclitaxel-eluting stent (PTX), a recently developed drug-eluting stent (DES), to conventional therapy for femoropopliteal (FP) lesions, the incidence and risk factors of the repetition of reintervention after DES implantation in clinical practice remained unrevealed. METHODS: This was a subanalysis of the ZEPHYR (ZilvEr PTX for tHe Femoral ArterY and Proximal Popliteal ArteRy) study, enrolling FP lesions undergoing endovascular therapy (EVT) with DES implantation. The current study analyzed the 2-year database including 583 FP lesions in 495 patients undergoing preoperative intravascular ultrasound imaging before DES implantation. The primary outcome measure was re-re-EVT, defined as undergoing additional EVT more than once during the 2-year follow-up after DES implantation. The secondary outcome measure was re-EVT, defined as undergoing at least one additional EVT during the follow-up. RESULTS: Critical limb ischemia (CLI) was present in 28% of the study population, 23% had a history of EVT, and 43% had chronic total occlusion. Mean lesion length was 16 ± 10 cm, and intravascular ultrasound imaging-evaluated external elastic membrane area was 28 ± 10 mm2. The cumulative incidence rate of re-re-EVT at 2 years was estimated to be 14%, whereas that of re-EVT was 31%. After multivariate analysis, CLI and smaller external elastic membrane area were independently associated with the outcome. CONCLUSIONS: The incidence and risk factors of the repetition of reintervention after DES implantation for FP lesions were revealed. The current findings suggest that DES implantation might be a careful indication in CLI cases especially with a small vessel.

Effect of Optimal Medical Therapy Before Procedures on Outcomes in Coronary Patients Treated With Drug-Eluting Stents.

It has not been established whether the achievement of optimal medical therapy (OMT) before implantation of a drug-eluting stent has a clinical benefit for patients with stable coronary artery disease (CAD). This study included 3,004 patients with CAD treated with drug-eluting stent from 123 Japanese participating centers. The achievement of OMT was defined as control of blood pressure <130/80 mm Hg, hemoglobin A1c <7.0%, and low-density lipoprotein cholesterol <100 mg/dl. The primary end point was target vessel failure, a composite of death related to the target vessel, myocardial infarction, or clinically driven revascularization at 24 months after stent implantation. Immediately before the procedure, only 548 patients (18.2%) had achieved all 3 target criteria (the achieved OMT group), whereas the remaining 2,456 patients failed to achieve one or more criteria (the non-OMT group). At 24 months, the incidence of target vessel failure was 7.0% in the achieved OMT group versus 10.0% in the non-OMT group (hazard ratio 0.68, 95% CI 0.48 to 0.96, p = 0.03). The incidence of non-Q-wave myocardial infarction was also lower in the achieved OMT group than in the non-OMT group (0.5% vs 1.5%, p = 0.08). Multivariate logistic regression analysis identified that hemoglobin A1c <7.0% was the only protective predictor of 24-month target vessel failure (odds ratio 0.56, 95% CI 0.43 to 0.73, p <0.01). In conclusion, this study demonstrated that in patients with stable CAD scheduled for stent implantation, achievement of OMT before percutaneous coronary intervention significantly reduced subsequent cardiac events. Achievement of OMT is still insufficient in modern clinical practice.

Higher Hemoglobin A1c After Discharge Is an Independent Predictor of Adverse Outcomes in Patients With Acute Coronary Syndrome　- Findings From the PACIFIC Registry.

BACKGROUND: Optimal medical therapy (OMT) and the management of coronary risk factors are necessary for secondary prevention of major adverse cardiac and cerebrovascular events (MACCE) in post-acute coronary syndrome (ACS) patients. However, the effect of post-discharge patient adherence has not been investigated in Japanese patients. METHODS AND RESULTS: The Prevention of AtherothrombotiC Incidents Following Ischemic Coronary Attack (PACIFIC) registry was a multicenter, prospective observational study of 3,597 patients with ACS. Death or MACCE occurred in 229 patients between hospitalization and up to 1 year after discharge. Among 2,587 patients, the association between OMT adherence and risk factor control at 1 year and MACCE occurring between 1 and 2 years after discharge was assessed. OMT was defined as the use of antiplatelet agents, angiotensin-converting enzyme inhibitors, ß-blockers, and statins. Risk factor targets were: low-density lipoprotein-cholesterol <100 mg/dl, HbA1c <7.0%, non-smoking status, blood pressure <130/80 mmHg, and 18.5≤body mass index≤24.9 kg/m(2). The incidence of MACCE was 1.8% and associated with female sex (P=0.020), age ≥75 years (P=0.004), HbA1c ≥7.0% (P=0.004), LV ejection fraction <35% (P<0.001), estimated glomerular filtration rate <60 ml/min (P=0.008), and history of cerebral infarction (P=0.003). In multivariate analysis, lower post-discharge HbA1c was strongly associated with a lower risk of MACCE after ACS (P=0.004). CONCLUSIONS: Hyperglycemia after discharge is a crucial target for the prevention of MACCE in post-ACS patients. (Circ J 2016; 80: 1607-1614).

One-year outcomes of the U.S. and Japanese regulatory trial of the Misago stent for treatment of superficial femoral artery disease (OSPREY study).

OBJECTIVE: The purpose of this study was to assess the safety and efficacy of the Misago stent (Terumo Corp, Tokyo, Japan) in occlusive and stenotic superficial femoral artery (SFA) disease. METHODS: The safety and efficacy of the Misago SFA stent were evaluated prospectively in this initial collaboration trial between Japan and the United States. Because this trial enrolled patients mainly from Japan and the United States and because there is a question as to whether a race difference exists in SFA stent performance, the race difference on outcome was also analyzed. In addition, results were compared with a prior SFA stent trial. RESULTS: The Misago stent was implanted in 261 subjects with TransAtlantic Inter-Society Consensus (TASC) type A and type B SFA lesions (201 subjects in the United States, 50 in Japan, 9 in Taiwan, 1 in South Korea). The mean age of the patients was 69.3 ± 10.0 years, and the mean lesion length was 83.8 ± 41.3 mm. The overall 12-month primary patency rate and clinically driven target lesion revascularization were 82.9% and 13.0%, respectively. Regional differences within the Occlusive/Stenotic Peripheral Artery Revascularization Study (OSPREY) and outcomes between U.S. and Asian patients were similar, including primary patency (82.9% vs 83.0%; P = .889), clinically driven target lesion revascularization (13.4% vs 11.7%; P = .829), stent fracture rate (1.3% vs 0.0%; P = 1.000), and stent thrombosis rate (0.5% vs 0.0%; P = 1.000). CONCLUSIONS: OSPREY 12-month data showed satisfactory outcome of the Misago stent for the treatment of TASC type A and type B SFA lesions and appears to be comparable to recent stent trials. In addition, the lack of difference in outcome among races supports the value of international trials.

Long-term outcomes of catheter ablation of ventricular tachycardia in patients with structural heart disease.

BACKGROUND: Catheter ablation of ventricular tachycardia (VT) is feasible. However, the long-term outcomes for different underlying diseases have not been well defined. METHODS: Eighty-eight consecutive patients who underwent catheter ablation of VT using a three-dimensional mapping system were analyzed. The primary endpoint was any VT or ventricular fibrillation (VF) recurrence. Secondary endpoints were a composite of death or any VT/VF recurrence. Underlying heart diseases were remote myocardial infarction (remote MI) in 51 patients and non-ischemic cardiomyopathy in 37 (arrhythmogenic right ventricular cardiomyopathy [ARVC] in 18 patients, and dilated cardiomyopathy [NIDCM] in 19). RESULTS: Acute success was achieved in 82 of 88 (93%) patients. During a follow-up period of 39.2±4.6 months, VT recurred in 26 of 87 (30%), and VT/VF recurrence or death occurred in 39 of 87 (45%) patients. ARVC had better outcomes than NIDCM for the primary (p<0.05) and secondary endpoints (p<0.05). Remote MI-VT revealed a midrange outcome. CONCLUSIONS: The long-term outcomes after catheter ablation of VT varied according to the underlying heart disease. ARVC-VT ablation was associated with better long-term prognosis than NIDCM. Remote MI-VT demonstrated a midrange outcome.