Radial Artery Remodeling following Transradial Percutaneous Coronary Intervention in Men and Women: Insights from Serial Ultrahigh Frequency Ultrasonography.

BACKGROUND: Remodeling of the radial artery (RA) after transradial percutaneous coronary intervention (TRI) is under studied. OBJECTIVES: To examine the impact of TRI on RA diameter and intimal-medial thickness (IMT) in men and women using 55 Mhz ultrahigh frequency duplex ultrasound (UHFDU). METHODS: We performed UHFDU at 24 h and 90 days after non-emergent TRI in 41 patients (25 men, 16 women). Changes in RA diameter, IMT and RA injury were compared by patient gender. Multivariate linear regression was used to determine the predictors of RA diameter and IMT. RESULTS: Of the 41 patients, mean age was 66 ±â€¯9.8. Baseline RA diameter was larger in men vs. women (3.1 ±â€¯0.40 mm vs. 2.8 mm ±â€¯0.36, p = 0.02), however there were similar reductions in 90-day diameter (-0.57 ±â€¯0.32 mm vs. -0.64 ±â€¯0.40 mm, respectively; p = 0.48). Baseline IMT was also similar in men and women (0.28 ±â€¯0.04 vs. 0.27 ±â€¯0.06 mm; p = 0.37) and there were 0.073 ±â€¯0.11 mm (26%) and 0.05 ±â€¯0.080 mm (19%) increases in IMT noted, respectively (p < 0.0001 vs. baseline, p = 0.48 for men vs. women). Although UHFDU occasionally detected limited access site intimal tears (12%) at 90 days, frank dissections (2.4%), pseudoaneurysms (2.4%) and total occlusions (4.9%) were infrequent. Female gender correlated with smaller RA diameter at follow-up and there were no predictors of IMT. CONCLUSIONS: Following TRI, there is a 20% reduction in RA diameter and a 20-25% increase in IMT. Only gender predicted RA diameter. As a simple, noninvasive method to accurately depict the RA healing response following TRI, UHFDU may inform future clinical investigation in this area.

Daily Passive Muscle Stretching Improves Flow-Mediated Dilation of Popliteal Artery and 6-minute Walk Test in Elderly Patients with Stable Symptomatic Peripheral Artery Disease.

BACKGROUND: Patients with peripheral arterial disease (PAD) often have walking impairment due to insufficient oxygen supply to skeletal muscle. In aged rats, we have shown that daily stretching of calf muscles improves endothelium-dependent dilation of arterioles from the soleus muscle and increases capillarity and muscle blood flow during exercise. Therefore, we hypothesized that daily muscle stretching of calf muscles would improve endothelium-dependent vasodilation of the popliteal artery and walking function in PAD patients. METHODS: We performed a randomized, non-blinded, crossover study whereby 13 patients with stable symptomatic PAD were randomized to undergo either 4 weeks of passive calf muscle stretching (ankle dorsiflexion applied 30 min/d, 5 days/wk) followed by 4 weeks of no muscle stretching and vice versa. Endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent nitroglycerin-induced dilation of the popliteal artery and 6 minute walk test (6MWT) were evaluated at baseline and after each 4 week interval. RESULTS: After 4 weeks of muscle stretching, FMD and 6MWT improved significantly in the muscle stretching group vs. the control (FMD: 5.1 ±â€¯0.5% vs. 3.7 ±â€¯0.3%, P = 0.005; 6MWT continuous walking distance: 304 ±â€¯43 m vs. 182 ±â€¯34 m; P = 0.0006). No difference in nitroglycerin-induced dilation was found between groups (10.9 ±â€¯1.2 vs. 9.9 ±â€¯0.4%, P = 0.48). Post-stretching, 6MWT total walking distance was positively correlated with normalized FMD (R = 0.645, P = 0.02). CONCLUSIONS: Passive calf muscle stretching enhanced vascular endothelial function and improved walking function in elderly patients with stable symptomatic PAD. These findings merit further investigation in a prospective randomized trial.

A Randomized Trial of the Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Intermediate-Risk Pulmonary Embolism: The OPTALYSE PE Trial.

OBJECTIVES: The aim of this study was to determine the lowest optimal tissue plasminogen activator (tPA) dose and delivery duration using ultrasound-facilitated catheter-directed thrombolysis (USCDT) for the treatment of acute intermediate-risk (submassive) pulmonary embolism. BACKGROUND: Previous trials of USCDT used tPA over 12 to 24 h at doses of 20 to 24 mg for acute pulmonary embolism. METHODS: Hemodynamically stable adults with acute intermediate-risk pulmonary embolism documented by computed tomographic angiography were randomized into this prospective multicenter, parallel-group trial. Patients received treatment with 1 of 4 USCDT regimens. The tPA dose ranged from 4 to 12 mg per lung and infusion duration from 2 to 6 h. The primary efficacy endpoint was reduction in right ventricular-to-left ventricular diameter ratio by computed tomographic angiography. A major secondary endpoint was embolic burden by refined modified Miller score, measured on computed tomographic angiography 48 h after initiation of USCDT. RESULTS: One hundred one patients were randomized, and improvements in right ventricular-to-left ventricular diameter ratio were as follows: arm 1 (4 mg/lung/2 h), 0.40 (24%; p = 0.0001); arm 2 (4 mg/lung/4 h), 0.35 (22.6%; p = 0.0001); arm 3 (6 mg/lung/6 h), 0.42 (26.3%; p = 0.0001); and arm 4 (12 mg/lung/6 h), 0.48 (25.5%; p = 0.0001). Improvement in refined modified Miller score was also seen in all groups. Four patients experienced major bleeding (4%). Of 2 intracranial hemorrhage events, 1 was attributed to tPA delivered by USCDT. CONCLUSIONS: Treatment with USCDT using a shorter delivery duration and lower-dose tPA was associated with improved right ventricular function and reduced clot burden compared with baseline. The major bleeding rate was low, but 1 intracranial hemorrhage event due to tPA delivered by USCDT did occur.

Ultrahigh-resolution ultrasound characterization of access site trauma and intimal hyperplasia following use of a 7F sheathless guide versus 6F sheath/guide combination for transradial artery PCI: Results of the PRAGMATIC trial.

There exist limited data on the relative degree of acute injury and late healing of the radial artery after transradial artery (TRA) percutaneous coronary intervention (PCI) with a 7F sheathless guide catheter compared with a 6F sheath/guide combination. We used ultrahigh-resolution (55 MHz) vascular ultrasound to compare intimal-medial thickening (IMT) and early and late radial artery (RA) injury resulting from a sheathless 7F guide catheter versus a 6F sheath/guide combination for TRA-PCI. METHODS: Forty-one consecutive consenting patients undergoing elective nonemergent TRA-PCI at a single institution from June 2016 to December 2016 were included. Patients were randomized (stratified by sex) to undergo TRA-PCI using a 7F sheathless guide catheter versus a 6F sheath/6F guide combination. Ultrahigh-resolution vascular ultrasound (55MHz) of the RA access site was performed at 24hours and 90days post-TRA-PCI. The primary outcome of the study was a noninferiority comparison of radial artery IMT thickness at 90days. PCI success rates, fluoroscopy times, number of guides used, and crossover rates to a femoral approach were also compared. RESULTS: Baseline characteristics were similar between groups. Radial arterial IMT (mm) was similar between the 7F sheathless and 6F sheath/guide groups at 24hours (0.27 vs 0.29, respectively; P=.43) and at 90days (0.35 vs 0.34, respectively; P=.96). The P value for the noninferiority testing of a 0.07-mm limit was .002. Limited access site intimal tears were relatively common in both groups at 24hours (4 vs 5, P=.53) but often healed by 90days. Radial artery occlusion was infrequent at 90days (2 vs 1, P=.10), and no frank dissections were noted. PCI success rates (100% vs 95%, P=.59), fluoroscopy times (16 vs 12minutes, P=.17), number of guides used (1.1 vs 1.2, P=.48), and femoral crossover rates (0% vs 0%) were similar between the 2 respective groups. CONCLUSIONS: A 7F sheathless approach to TRA-PCI results in no more IMT and early or late RA trauma than a standard 6F sheath/guide combination, rendering the 7F sheathless technique an attractive option for complex TRA-PCI.

Sustained low clinical event rates in real-world patients receiving everolimus-eluting coronary stent system from a large, prospective, condition of approval study: 2-year clinical outcomes from the XIENCE V USA Study.

OBJECTIVES: This 2-year follow-up of the XIENCE V USA study examines both the long-term safety and effectiveness of the everolimus-eluting coronary stent system (EECSS) in real-world patients. BACKGROUND: The safety and effectiveness of EECSS at 1 year in real-world clinical settings have been demonstrated in XIENCE V USA trial with low rates of target lesion revascularization (TLR), cardiac death, myocardial infarction (MI), and stent thrombosis (ST). Data on whether efficacy is maintained after 1 year and the event rate of very late stent thrombosis (VLST) between 1 and 2 years have not yet been reported. METHODS: XIENCE V USA is a prospective, multicenter, single-arm, FDA required condition of approval study designed to examine the safety and effectiveness of EECSS in an all-inclusive, consecutively enrolled population from real-world clinical settings. Clinical end-point events, including ST, cardiac death, MI, and revascularization were adjudicated by an independent Clinical Events Committee. RESULTS: Four thousand eight hundred and seventy-three (96.4%) out of 5,054 participants (1,875 standard-risk; 3,059 extended-risk) reached 2-year follow-up. The 2-year rate of Academic Research Consortium (ARC)-defined definite and probable ST was 0.96% (95% CI 0.70-1.28) in the overall population and 0.34% (95% CI 0.12-0.74) and 1.33% (95% CI 0.95-1.81) in the standard-risk and extended-risk cohorts, respectively. The rate of VLST was 0.06% in the overall population, 0.0% in the standard-risk, and 0.10% in the extended-risk cohorts. The 2-year composite rate of cardiac death and ARC-defined MI was 8.9% (95% CI 8.08-9.70) in the overall population and 5.6% (95% CI 4.61-6.78) and 10.8% (95% CI 9.71-11.94) in the standard-risk and extended-risk cohorts, respectively. CONCLUSION: Low event rates observed at 1 year were maintained through 2 years. Despite the increased number of patients who discontinued dual antiplatelet therapy by 2 years, the ST rate remained consistently low, and <1% at 2 years due to low VLST occurrence. These results demonstrate continued safety and effectiveness of the XIENCE V everolimus-eluting stent in a highly complex, real-world patient population through 2 years.

A new era of prospective real-world safety evaluation primary report of XIENCE V USA (XIENCE V Everolimus Eluting Coronary Stent System condition-of-approval post-market study).

OBJECTIVES: The XIENCE V USA (XIENCE V Everolimus Eluting Coronary Stent System Condition-of-Approval Post-Market study) sought to: 1) evaluate the safety of everolimus-eluting coronary stent systems (EECSS) in a contemporary cohort of real-world subjects; and 2) prospectively test the quality of event reporting with analysis of matched patients from the randomized SPIRIT IV (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions) trial. BACKGROUND: Randomized trials have demonstrated the safety and efficacy of EECSS in selected "standard-risk" patients. METHODS: The XIENCE V USA trial was a prospective, multicenter, single-arm study in unselected patients. The primary endpoint was Academic Research Consortium (ARC)-defined definite and probable stent thrombosis (ST); the co-primary endpoint was the composite of cardiac death and myocardial infarction at 1 year. Secondary analyses included: 1) stratification by standard-risk and extended-risk cohorts; and 2) late ST after dual antiplatelet therapy interruption. RESULTS: Of 5,054 participants (1,875 standard-risk; 3,179 extended-risk), 4,958 (98.1%) reached 1-year follow-up. The rate of ARC-defined definite and probable ST was 0.84% (95% confidence interval [CI]: 0.60% to 1.14%) in the overall population and 0.33% (95% CI: 0.12% to 10.72%) and 1.14% (95% CI: 0.80% to 11.58%) in the standard-risk and extended-risk cohorts, respectively. No late ST was observed after dual antiplatelet therapy interruption in either cohort after 6 months. The composite rate of cardiac death and ARC-defined myocardial infarction was 6.5% (95% CI: 5.79% to 17.17%) in the overall population, 3.8% (95% CI: 2.98% to 14.78%) in the standard-risk cohort, and 8.0% (95% CI: 7.09% to 19.02%) in the extended-risk cohort. CONCLUSIONS: This study comprehensively reports ST rates for EECSS in a contemporary real-world population. The absence of ST after dual antiplatelet therapy interruption beyond 6 months in standard-risk and high-risk patients is notable. Consistent safety outcomes between matched standard-risk cohorts from the XIENCE V USA study and the SPIRIT IV randomized trial suggest that this study affords a reliable benchmark for understanding the safety of EECSS in the context of real-world clinical practice. (XIENCE V Everolimus Eluting Coronary Stent System [EECSS] USA Post-Approval Study; NCT00676520).

Usage patterns and 2-year outcomes with the TAXUS express stent: results of the US ARRIVE 1 registry.

BACKGROUND: It is unclear how well the long-term safety and effectiveness of drug-eluting stents observed in tightly defined randomized controlled trials (RCT) translates to expanded use in routine practice. METHODS: The FDA-mandated TAXUS Express(2) ARRIVE 1 postmarket registry was designed to consecutively enroll patients receiving > or = 1 TAXUS stent in low-, medium-, and high-volume US sites (n = 50). All cardiac events plus an additional 20% sample of records were monitored and all endpoints were independently adjudicated. RESULTS: Detailed follow-up data through 2 years were compiled for 2,487 patients (95%). Simple-use (on-label) ARRIVE 1 patients (35%) had outcomes similar to 4 pooled TAXUS RCTs for death (3.5% vs. 3.4%, respectively, P = 0.78), Q-wave myocardial infarction (QWMI, 0.7% vs. 0.9%, P = 0.72), and stent thrombosis (ST, 2.2% vs. 1.2%, P = 0.12), but lower target vessel revascularization (7.8% vs. 13.4%, P < 0.0001). Compared with simple-use, cases representing expanded use to treat broader patient/lesion characteristics showed higher 2-year rates for death (7.4% vs. 3.5%, respectively, P = 0.0003), target lesion revascularization (9.4% vs. 5.8%, P = 0.0031), and ST (3.4% vs. 2.2%, P = 0.061, concentrated early in the first year). CONCLUSIONS: By including methods usually found in RCT, ARRIVE 1 captured a broad spectrum of disease treated in standard practice with high levels of ascertainment of clinical outcomes. In the more complicated cases, expectedly higher adverse event rates were seen compared to that found in the simple-use cases or pivotal RCT. These results have now been included in the Directions for Use, to aid in physician and patient decision-making.