Total body recumbent stepping vs treadmill walking in supervised exercise therapy: A pilot study

Background: Treadmill walking is the most commonly recommended exercise modality in supervised exercise therapy (SET) for peripheral artery disease (PAD); however, other modalities may be equally effective and more tolerable for patients. The primary aim of this single-blind, randomized pilot study was to compare the feasibility, safety, and preliminary efficacy of a treadmill walking (TM) versus a total body recumbent stepping (TBRS) exercise program for treatment of PAD. Methods: Participants ( n = 19) enrolled in a 12-week SET program and were randomized to either a TM ( n = 9) or TBRS ( n = 10) exercise group that followed current SET exercise guidelines. Feasibility, safety, and efficacy outcomes were assessed. Results: SET attendance was 86% and 71%, respectively, for TBRS and TM groups ( p = 0.07). Session exercise dose (metabolic equivalents of task [MET] minutes) (mean [SD]) for TM was 117.6 [27.4] compared to 144.7 [28.7] in the TBRS group ( p = 0.08). Study-related adverse events were nine in 236 training hours and three in 180 training hours for the TBRS and TM groups, respectively. There were no significant differences between groups for improvement in 6-minute walk distance (mean [SD]) (TM: 133.2 ft [53.5] vs TBRS: 154.8 ft [49.8]; p = 0.77) after adjusting for baseline 6-minute walk distance. Conclusion: This is the first randomized study comparing TBRS to TM exercise in SET using current SET guidelines. This pilot study showed that TBRS is a feasible and safe exercise modality in SET. This study provides preliminary efficacy of the use of TBRS exercise in SET programs following current guidelines. Larger studies should be conducted to confirm these findings.

Cardiovascular manifestations of hypermobile Ehlers–Danlos syndrome and hypermobility spectrum disorders

Introduction: Mitral valve prolapse and aortic root dilatation are reported in association with hypermobile Ehlers–Danlos syndrome (hEDS), but the full phenotypic spectrum of cardiovascular complications in this condition has not been studied in the aftermath of updated nosology and diagnostic criteria. Methods: We performed a retrospective review of 258 patients (> 94% adults) referred to a multidisciplinary clinic for evaluation of joint hypermobility between January 2017 and December 2020 and diagnosed with hEDS or a hypermobility spectrum disorder (HSD) to determine the incidence and spectrum of cardiovascular involvement. Results: Mitral valve prolapse was present in 7.5% and thoracic aortic dilatation in 15.2%. Aortic dilatation was more frequent in individuals with hEDS (20.7%) than with HSD (7.7%) and similarly prevalent between males and females, although was mild in > 90% of females and moderate-to-severe in 50% of males. Five individuals (1.9%) with hEDS/HSD had extra-aortic arterial involvement, including cervical artery dissection (CeAD, n = 2), spontaneous coronary artery dissection (SCAD, n = 2), and SCAD plus celiac artery pseudoaneurysm ( n = 1). This is the first series to report the prevalence of CeAD and SCAD in hEDS/HSD. Conclusions: Cardiovascular manifestations in adults with hEDS/HSD, especially females, are typically mild and readily assessed by echocardiography. Since the risk of progression has not yet been defined, adults with hEDS/HSD who are found to have aortic dilatation at baseline should continue ongoing surveillance to monitor for progressive dilatation. Cardiovascular medicine specialists, neurologists, and neurosurgeons should consider hEDS/HSD on the differential for patients with CeAD or SCAD who also have joint hypermobility.

Smaller size is more suitable for pharmacotherapy among undersized abdominal aortic aneurysm: a systematic review and meta-analysis

Background: Pharmacotherapy for undersized abdominal aortic aneurysm (AAA) is a clinical unmet need. Randomized controlled trials (RCTs) have failed to show effectiveness despite countless promising data in preclinical studies. We aimed to identify the population with undersized AAAs (30–54 mm) who potentially benefit from pharmacotherapy. Methods: In accordance with the PRISMA statement, we conducted a systematic review and meta-analysis of placebo-controlled RCTs. The primary outcome was mean difference (MD) in annual growth rate (< 0 favors pharmacotherapy), and the secondary outcome was aneurysm-related events (diameters ⩾ 55 mm, ruptures, or referral to surgery). Results: Our search strategy identified eight RCTs (six trials on antibiotics [ABx], two on renin-angiotensin system inhibitors [RAS-I]) with a total of 1325 patients. The mean of baseline diameters ranged from 33.1 mm to 43.1 mm. Neither ABx nor RAS-I showed significant differences in MD. Multivariable random-effects restricted maximum likelihood meta-regression revealed a statistically significant linear relationship between baseline diameter and MD (coefficient 0.15 [95% CI 0.0011, 0.30], p = 0.049) but not for the follow-up period ( p = 0.28) and duration of treatment ( p = 0.11). In line with this result, ABx with baseline diameter < 40 mm significantly reduced MD (−1.03 mm/year [95% CI −1.64, −0.42], p = 0.001) and a borderline significant difference in aneurysm-related events (HR 0.53 [95% CI 0.28, 1.00], p = 0.05), whereas the other groups ⩾ 40 mm never demonstrated effectiveness. Fixed-effect models did not change the results. No evidence of publication bias was detected. Conclusion: Undersized AAAs < 40 mm can potentially benefit from pharmacotherapy. Future RCTs should consider preferentially including undersized AAA with smaller diameters.

Safety of home-based exercise for people with intermittent claudication: A systematic review

Intermittent claudication (IC) is a classic symptom of peripheral artery disease, with first line treatment being supervised exercise therapy (SET). Despite this, SET is frequently underutilised, and adherence is often poor. An alternative option are home-based exercise programmes (HBEP). Although HBEPs are well tolerated, to the authors’ knowledge, no research has assessed their safety. The aim of this review was to assess the safety of HBEPs in people living with IC. We performed an electronic search of the MEDLINE, CINAHL, and Cochrane Library databases. The main parameter of interest was complication rate, calculated as the number of related adverse events per patient-hours. Subanalysis was undertaken to determine differences in safety for studies that did and did not include pre-exercise cardiac screening, and for studies with exercise at low, moderate, and high levels of claudication pain. Our search strategy identified 8693 results, of which 27 studies were included for full review. Studies included 1642 participants completing 147,810 patient-hours of home-based exercise. Four related adverse events were reported, three of which were cardiac in origin, giving an all-cause complication rate of one event per 36,953 patient-hours. Three of these events occurred following exercise to high levels of claudication pain, and one occurred with pain-free exercise. All four events occurred in studies without cardiac screening. Based on the low number of related adverse events, HBEPs appear to be a safe method of exercise prescription for people with IC. Our results strengthen the rationale for providing alternative exercise options for this population. PROSPERO Registration No.: CRD42021254581

Macrovascular and microvascular responses to prolonged sitting with and without bodyweight exercise interruptions: A randomized cross-over trial

Exposure to uninterrupted prolonged sitting leads to macro- and microvascular complications, which can contribute to increased cardiovascular disease risk. This study investigated the macrovascular and microvascular responses to 3 h of sitting that was: (i) uninterrupted (CON); and (ii) interrupted every 20 min with 1 min light intensity half squats plus calf raises (EX). Twenty healthy participants (21 [SD: 2] years; 21.5 [SD: 1.6] kg/m2) were recruited to participate in this randomized cross-over trial. Macrovascular function was quantified using brachial–ankle pulse wave velocity (baPWV) and the lower- and upper-limb arterial stiffness index (ASI). Microvascular function was quantified as the medial gastrocnemius tissue oxygen saturation (StO2) area under the curve (AUC) during reactive hyperemia. The baPWV did not significantly change with time ( p = 0.594) or by condition ( p = 0.772). The arm ASI increased by 3.6 (95% CI: 0.7 to 6.6, effect size [ES] = 0.27) with a nonsignificant condition effect ( p = 0.219). There was a significant interaction effect for leg ASI ( p = < 0.001), with ASI increasing (impairment) by 18.7 (95% CI: 12.1 to 25.3, ES = 0.63) for CON and decreasing (improvement) by −11.9 (95% CI: −18.5 to −5.3, ES = 0.40) for EX compared to presitting. Similarly, the AUC decreased (detrimental) by 18% (Δ = −321, 95% CI: −543 to −100, ES = 0.32) for CON and increased by 32% (Δ = 588, 95% CI: 366 to 809, ES = 0.59) for EX. The leg ASI was inversely associated with StO2 AUC (interclass correlation coefficient: −0.66, 95% CI: −0.51 to −0.77). These preliminary findings suggest that regularly interrupting prolonged sitting with simple bodyweight exercises may help to preserve lower-limb vascular function.

Apixaban Discontinuation for Invasive Or major Surgical procedures (ADIOS): A prospective cohort study

Background: Apixaban pharmacokinetic properties and some clinical reports suggest cessation 48 hours prior to surgery is safe, but this has not been demonstrated in a naturalistic setting. We sought to measure the residual apixaban exposure in patients who had apixaban held as part of standard of care perioperative management. Methods: This was a prospective, observational study of patients in whom apixaban plasma concentration and anti-Xa activity were measured while at steady state apixaban dosing and again immediately prior to surgery. Clinical management of cessation and resumption of apixaban was at the discretion of the treating physician. Results: Paired blood samples were provided by 111 patients. Ninety-four percent (104/111) of patients had measured apixaban concentrations of ⩽ 30 ng/mL. Only one patient had a value > 50 ng/mL. The median time between the self-reported last dose and presurgery blood sampling was 76 hours (range 32–158) for those who achieved concentrations ⩽ 30 ng/mL and 59 hours (range 49–86) for those > 30 ng/mL. Measured anti-Xa activity correlated well with apixaban exposure. Clinically significant nonmajor bleeding was reported in one patient at 1 week postsurgery. There was one venous thromboembolic event and one stroke in the perioperative period. Conclusion: In a naturalistic setting with a heterogeneous patient population, apixaban discontinuation for at least 48 hours before a procedure resulted in a clinically insignificant degree of anticoagulation prior to a surgical procedure. ClinicalTrials.gov Identifier: NCT02935751