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AimsIcosapent ethyl (IPE) significantly reduced ischaemic events in statin-treated patients with atherosclerosis or diabetes and elevated triglycerides in REDUCE-IT, including large reductions in myocardial infarction and elective, urgent, and emergent coronary revascularization. However, the mechanisms driving this clinical benefit are not fully known. The EVAPORATE trial demonstrated that IPE significantly reduced plaque burden. No study to date has assessed the impact of IPE on coronary physiology. Fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) data sets (FFRCT) applies computational fluid dynamics to calculate FFR values in epicardial coronary arteries. Our objective was to assess the impact of IPE on coronary physiology assessed by FFRCT using imaging data from EVAPORATE.Methods and resultsA total of 47 patients and of 507 coronary lesions at baseline, 9 months, and 18 months with coronary CTA and FFRCT were studied in a blinded core lab. The pre-specified primary endpoint was the FFRCT value in the distal coronary segment from baseline to follow-up in the most diseased vessel per patient using IPE compared with placebo. The pre-specified secondary endpoint was the change in translesional FFRCT (ΔFFRCT) across the most severe (minimum 30% diameter stenosis) coronary lesion per vessel. Baseline FFRCT was similar for IPE compared with placebo (0.83 ± 0.08 vs. 0.84 ± 0.08, P = 0.55). There was significant improvement in the primary endpoint, as IPE improved mean distal segment FFRCT at 9- and 18-month follow-up compared with placebo (0.01 ± 0.05 vs. -0.05 ± 0.09, P = 0.02, and -0.01 ± 0.09 vs. -0.09 ± 0.12, P = 0.03, respectively). ΔFFRCT in 140 coronary lesions was improved, although not statistically significant, with IPE compared with placebo (-0.06 ± 0.08 vs. -0.09 ± 0.1, P = 0.054).ConclusionIcosapent ethyl demonstrated significant benefits in coronary physiology compared with placebo. This early and sustained improvement in FFRCT at 9- and 18-month follow-up provides mechanistic insight into the clinical benefit observed in the REDUCE-IT trial. Furthermore, this is the first assessment of FFRCT to determine drug effect.

AIMS: Residual cardiovascular risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total events, but the mechanisms of benefit are not fully understood. EVAPORATE evaluated the effects of IPE on plaque characteristics by coronary computed tomography angiography (CCTA). Given the conclusion that the IPE-treated patients demonstrate that plaque burden decreases has already been published in the primary study analysis, we aimed to demonstrate whether the use of an analytic technique defined and validated in histological terms could extend the primary study in terms of whether such changes could be reliably seen in less time on drug, at the individual (rather than only at the cohort) level, or both, as neither of these were established by the primary study result. METHODS AND RESULTS: EVAPORATE randomized the patients to IPE 4 g/day or placebo. Plaque morphology, including lipid-rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH), was assessed using the ElucidVivo® (Elucid Bioimaging Inc.) on CCTA. The changes in plaque morphology between the treatment groups were analyzed. A neural network to predict treatment assignment was used to infer patient representation that encodes significant morphological changes. Fifty-five patients completed the 18-month visit in EVAPORATE with interpretable images at each of the three time points. The decrease of LRNC between the patients on IPE vs. placebo at 9 months (reduction of 2 mm3 vs. an increase of 41 mm3, p = 0.008), widening at 18 months (6 mm3 vs. 58 mm3 increase, p = 0.015) were observed. While not statistically significant on a univariable basis, reductions in wall thickness and increases in cap thickness motivated multivariable modeling on an individual patient basis. The per-patient response assessment was possible using a multivariable model of lipid-rich phenotype at the 9-month follow-up, p

Sustained clinical and hemodynamic benefit after revascularization for chronic limb-threatening ischemia (CLTI) is needed to resolve symptoms and prevent limb loss. We sought to compare rates of clinical and hemodynamic failure as well as resolution of initial and prevention of recurrent CLTI after endovascular (ENDO) vs bypass (OPEN) revascularization in the Best-Endovascular-versus-best-Surgical-Therapy-in-patients-with-CLTI (BEST-CLI) trial. As planned secondary analyses of the BEST-CLI trial, we examined the rates of (1) clinical failure (a composite of all-cause death, above-ankle amputation, major reintervention, and degradation of WIfI stage); (2) hemodynamic failure (a composite of above-ankle amputation, major and minor reintervention to maintain index limb patency, failure to an initial increase or a subsequent decrease in ankle brachial index of 0.15 or toe brachial index of 0.10, and radiographic evidence of treatment stenosis or occlusion); (3) time to resolution of presenting CLTI symptoms; and (4) incidence of recurrent CLTI. Time-to-event analyses were performed by intention-to-treat assignment in both trial cohorts (cohort 1: suitable single segment great saphenous vein [SSGSV], N = 1434; cohort 2: lacking suitable SSGSV, N = 396), and multivariate stratified Cox regression models were created. In cohort 1, there was a significant difference in time to clinical failure (log-rank P <.001), hemodynamic failure (log-rank P <.001), and resolution of presenting symptoms (log-rank P =.009) in favor of OPEN. In cohort 2, there was a significantly lower rate of hemodynamic failure (log-rank P =.006) favoring OPEN, and no significant difference in time to clinical failure or resolution of presenting symptoms. Multivariate analysis revealed that assignment to OPEN was associated with a significantly lower risk of clinical and hemodynamic failure in both cohorts and a significantly higher likelihood of resolving initial and preventing recurrent CLTI symptoms in cohort 1, including after adjustment for key baseline patient covariates (end-stage renal disease [ESRD], prior revascularization, smoking, diabetes, age >80 years, WIfI stage, tissue loss, and infrapopliteal disease). Factors independently associated with clinical failure included age >80 years in cohort 1 and ESRD across both cohorts. ESRD was associated with hemodynamic failure in cohort 1. Factors associated with slower resolution of presenting symptoms included diabetes in cohort 1 and WIfI stage in cohort 2. Durable clinical and hemodynamic benefit after revascularization for CLTI is important to avoid persistent and recurrent CLTI, reinterventions, and limb loss. When compared with ENDO, initial treatment with OPEN surgical bypass, particularly with available saphenous vein, is associated with improved clinical and hemodynamic outcomes and enhanced resolution of CLTI symptoms. [ABSTRACT FROM AUTHOR]

PurposeMagnetic resonance imaging (MRI) is a high-cost imaging modality, and an optimized encounter ideally provides high-quality care, patient satisfaction, and capacity utilization. Our purpose was to assess the effectiveness of team training and its impact on patient show-up and completion rates for their MRI examinations.Materials and methodsA total of 97,712 patient visits from three tertiary academic medical centers over 1-year intervals were evaluated, totaling 49,733 visits at baseline and 47,979 after training. Each center's MRI team received team training skill training including advanced communication and team training techniques training. This training included onsite instruction including case simulation with scenarios requiring appropriate behavioral and communicative interventions. Orientation and training also utilized customized online tools and proctoring. The study completion rate and patient show-up rate during consecutive year-long intervals before and after team training were compared to assess its effectiveness. Two-sided chi-square tests for proportions using were applied at a 0.05 significance level.ResultsDespite differing no-show rates (5-22.2%) and study incompletion rates (0.7-3.7%) at the three academic centers, the combined patients' data showed significant (P < 0.0001) improvement in the patients' no-show rates (combined decreases from 11.2% to 8.7%) and incompletion rates (combined decreases from 2.3% to 1.4%).ConclusionOur preliminary results suggest training of the imaging team can improve the no-show and incompletion rates of the MRI service, positively affecting throughput and utilization. Team training can be readily implemented and may help address the needs of the current cost-conscious and consumer-sensitive healthcare environment. J. MAGN. RESON. IMAGING 2016;44:1040-1047.

BackgroundWe compared the effects of two uniquely different lower extremity power training interventions on changes in muscle power, physical performance, neuromuscular activation, and muscle cross sectional area in mobility-limited older adults.MethodsFifty-two subjects (78±5 years, short physical performance battery score: 8.1±1) were randomized to either 16 weeks of progressive high velocity resistance training performed at low external resistance (40% of the 1-repetition maximum [1-RM] [LO]) or high external resistance (70% of 1RM [HI]). Both groups completed three sets of leg and knee extension exercises at maximum voluntary velocity, two times per week. Neuromuscular activation was assessed using surface electromyography and muscle cross sectional area (CSA) was measured using computed tomography.ResultsAt 16 weeks, LO and HI exhibited significant and similar within-group increases of leg extensor peak power (~34% vs ~42%), strength (~13% vs ~19%), and SPPB score (1.4±0.3 vs 1.8±0.3 units), respectively (all P < .03). Improvements in neuromuscular activation occurred in LO (P = .03) while small gains in mid-thigh muscle CSA were detected in LO (1.6%, P = .35) and HI (2.1%, P = .17). No significant between-group differences were evident for any measured parameters (all P > .25).ConclusionsHigh velocity resistance training with low external resistance yields similar improvements in muscle power and physical performance compared to training with high external resistance in mobility-limited elders. These findings may have important implications for optimizing exercise interventions for older adults with mobility limitations.

BackgroundTreatment with aspirin and a P2Y12 inhibitor is commonly used in patients with cardiovascular disorders. The overall effect of such treatment on all-cause mortality is unknown. In the Dual Antiplatelet Therapy (DAPT) Study, continuation of dual antiplatelet therapy beyond 12 months after coronary stenting was associated with an unexpected increase in non-cardiovascular death. In view of the potential public health importance of these findings, we aimed to assess the effect of extended duration dual antiplatelet therapy on mortality by doing a meta-analysis of all randomised, controlled trials of treatment duration in various cardiovascular disorders.MethodsWe searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomised controlled trials assessing the effect of extended duration versus no or short duration dual antiplatelet therapy, published before Oct 1, 2014. We did a meta-analysis to pool results with a hierarchical Bayesian random-effects model. The primary outcomes were hazard ratios comparing rates of all-cause, cardiovascular, and non-cardiovascular death.FindingsIncluding the DAPT Study, we identified 14 eligible trials that randomly assigned 69,644 participants to different durations of dual antiplatelet therapy. Compared with aspirin alone or short duration dual antiplatelet therapy (≤6 months), continued treatment was not associated with a difference in all-cause mortality (hazard ratio [HR] 1·05, 95% credible interval [CrI] 0·96-1·19; p=0·33). Similarly, cardiovascular (1·01, 0·93-1·12; p=0·81) and non-cardiovascular mortality (1·04, 0·90-1·26; p=0·66) were no different with extended duration versus short duration dual antiplatelet therapy or aspirin alone.InterpretationExtended duration dual antiplatelet therapy was not associated with a difference in the risk of all-cause, cardiovascular, or non-cardiovascular death compared with aspirin alone or short duration dual antiplatelet therapy.FundingNone.

PurposeThis longitudinal study examined the major physiological mechanisms that determine the age-related loss of lower extremity muscle power in two distinct groups of older humans. We hypothesized that after ~3 years of follow-up, mobility-limited older adults (mean age: 77.2 ± 4, n = 22, 12 females) would have significantly greater reductions in leg extensor muscle power compared to healthy older adults (74.1 ± 4, n = 26, 12 females).MethodsMid-thigh muscle size and composition were assessed using computed tomography. Neuromuscular activation was quantified using surface electromyography and vastus lateralis single muscle fibers were studied to evaluate intrinsic muscle contractile properties.ResultsAt follow-up, the overall magnitude of muscle power loss was similar between groups: mobility-limited: -8.5 % vs. healthy older: -8.8 %, P > 0.8. Mobility-limited elders had significant reductions in muscle size (-3.8 %, P < 0.01) and strength (-5.9 %, P < 0.02), however, these parameters were preserved in healthy older (P ≥ 0.7). Neuromuscular activation declined significantly within healthy older, but not in mobility-limited participants. Within both groups, the cross-sectional areas of type I and IIA muscle fibers were preserved while substantial increases in single fiber peak force (>30 %), peak power (>200 %) and unloaded shortening velocity (>50 %) were elicited at follow-up.ConclusionDifferent physiological mechanisms contribute to the loss of lower extremity muscle power in healthy older and mobility-limited older adults. Neuromuscular changes may be the critical early determinant of muscle power deficits with aging. In response to major whole muscle decrements, major compensatory mechanisms occur within the contractile properties of surviving single muscle fibers in an attempt to restore overall muscle power and function with advancing age.

There has been significant variability in practice patterns and equipoise regarding treatment approach for chronic limb-threatening ischemia (CLTI). We aimed to assess treatment preferences of Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) investigators prior to and following the trial. An electronic 60-question survey was sent to 1180 BEST-CLI investigators in 2022, after trial conclusion and before announcement of results. Investigators' preferences were assessed across clinical scenarios for both open (OPEN) and endovascular (ENDO) revascularization strategies. Vascular surgeon (VS) surgical and ENDO preferences were compared with a 2010 survey administered to prospective investigators before trial funding. For the 2022 survey, the response rate was 20.2% and was comprised of VSs (76.3%), interventional cardiologists (11.4%) and interventional radiologists (11.6%). The majority (72.6%) were in academic practice and 39.1% were in practice for >20 years. During initial CLTI work-up, 65.8%, 42.6%, and 55.9% of respondents always or usually ordered an arterial duplex, computed tomography angiography, and vein mapping, respectively. The most common practice distribution between ENDO and OPEN procedures was 70/30. Postoperatively, a majority reported performing routine duplex surveillance of vein bypass (99%), prosthetic bypass (81.9%), and ENDO interventions (86%). A minority reported always or usually using the wound, ischemia, and foot infection (WIfI) criteria (25.8%), GLASS (8.3%), and a risk calculator (14.8%). More than one-half (52.9%) agreed that the statement "no bridges are burned with an ENDO-first approach" was false. Intervention choice was influenced by availability of the operating room or ENDO suite, personal schedule, and personal skill set in 30.1%, 18.0%, and 45.9% of respondents, respectively. Most respondents reported routinely using paclitaxel-coated balloons (88.1%) and stents (67.5%); however, 73.3% altered practice when safety concerns were raised. Among surgeons, 17.8%, 2.9%, and 10.3% reported performing >10 annual alternative autogenous vein bypasses, composite vein composite vein bypasses, and bypasses to pedal targets, respectively. Among all interventionalists, 8%, 24%, and 8% reported performing >10 annual radial access procedures, pedal or tibial access procedures, and pedal loop revascularizations. The majority (89.1%) of respondents felt that CLTI teams improved care; however, only 23.2% had a defined team. The effectiveness of the teamwork at institutions was characterized as highly effective in 42.5%. When comparing responses by VSs to the 2010 survey, there were no changes in preferred treatment based on Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) II classification or conduit preference. In 2022, OPEN surgery was preferred more for a popliteal occlusion. For clinical scenarios, there were no differences except a decreased proportion of respondents who felt there was equipoise for major tissue loss for major tissue loss (43.8% vs 31.2%) and increased ENDO choice for minor tissue loss (17.6% vs 30.8%) (P <.05). There is a wide range of practice patterns among vascular specialists treating CLTI. The majority of investigators in BEST-CLI had experience in both advanced OPEN and ENDO techniques and represent a real-world sample of technical expertise. Over the course of the decade of the BEST-CLI trial, there was overall similar equipoise among VSs. [ABSTRACT FROM AUTHOR]