Test-retest Reliability and Minimal Detectable Change in Exercise Oximetry in Claudicants.

BACKGROUND: Exercise transcutaneous oxygen pressure measurement (Exercise-TcPO2) can be used to diagnose Lower Extremity Artery Disease (LEAD) and allows the quantification of limb ischemia during exercise on treadmill. Exercise-TcPO2 test-retest reliability in patients with LEAD and severe walking impairment is unknown. The aim of this study was to evaluate the test-retest reliability, standard error of measurement (SEM), and Minimal Detectable Change (MDC) of exercise-TcPO2 in patients with claudication. METHODS: Data were collected from patients that performed 2 treadmill tests within a 1-month interval. Delta from Rest of Oxygen Pressure (DROP) values were measured at both buttocks (proximal) and both calves (distal). Test-retest reproducibility was assessed by recording transcutaneous oximetry measurements twice and expressed as SEM and intra-class correlation coefficients. MDC was calculated using the formula MDC = SEM x 1.96 x √ 2. RESULTS: Twenty eight LEAD patients (61 ± 9 years old) were included. Intra-class correlation coefficients were 0.66 [0.50, 0.79] and 0.65 [0.49, 0.79] for the proximal and distal levels, respectively. The SEM of DROP at the proximal and distal levels were 7 [6, 9] mm Hg and 9 [8, 11] mm Hg, respectively. The SEM for all (proximal and distal) DROP values was 8 [7, 10] mm Hg and the MDC of DROP was 23 mm Hg. CONCLUSIONS: Exercise-TcPO2 with measurement of DROP values has a moderate test-retest reliability in LEAD patients with a maximal walking distance ≤ 300m. For an individual, an improvement or deterioration in DROP of ≥ 23 mm Hg after an intervention would be required to be 95% confident that the change is significant. It should be considered in evaluating the impact of treatment in patients with claudication.

Simplification of ankle-brachial-index measurement using Doppler-waveform classification in symptomatic patients suspected of lower extremity artery disease.

Objectives: Ankle-brachial index (ABI) is commonly used for screening lower extremity peripheral artery disease (PAD) according to the international guidelines. Arterial Doppler waveform recordings is a tool to diagnose and assess PAD severity. We hypothesized that ABI measurement could be simplified by measuring only the pressure where the best arterial flow is recorded. The aim of this study was to evaluate the concordance between ABI performed according to the American Heart Association guidelines (AHA-ABI) and ABI measured according to best arterial waveform (FLOW-ABI). Design: This was a monocentric cross-sectional study. Methods: We included patients with exertional limb symptoms suspected of PAD. Arterial Doppler waveforms and ABI were acquired on both lower extremities at the pedis and tibial posterior arteries. Each arterial waveform was classified using the Saint-Bonnet classification. Concordances were analyzed with the kappa coefficient (confidence interval 95%). Exercise PAD study was registered n° NCT03186391. Results: In total, one hundred and eighty-eight patients (62+/-12 years and 26.8+/-4.5 kg/m2) with exertional limb symptoms were included from May 2016 to June 2019. On each extremity, FLOW-ABI had excellent concordance for the diagnosis of PAD with the AHA-ABI with a kappa of 0.95 (95% CI: 0.90, 0.99) in the right extremity and 0.91 (95% CI: 0.86, 0.97) in the left extremity. Conclusion: There is almost perfect concordance between AHA-ABI and FLOW-ABI. Thus, ABI can be simplified into five pressure measurements instead of seven in patient suspected of PAD with exertional limb symptoms. The question remains in patients with chronic limb ischemia.

Performance of finger systolic blood pressure measurement to detect digital occlusive arterial disease in systemic sclerosis.

OBJECTIVE: Digital ulcers related to digital occlusive arterial disease (DOAD) are frequent in patients with SSc. Finger systolic blood pressure (FSBP) and digital-brachial pressure index (DBI) using laser Doppler flowmetry constitute a non-invasive means of detecting DOAD in SSc, although thresholds have yet to be established for defining DOAD. The purpose of this study was to ascertain FSBP and DBI thresholds to detect DOAD in SSc patients. The intra/interday reproducibility of curve reading by four vascular physicians in relation to finger pressure measurement was also investigated. METHODS: SSc patients were followed in this single-centre study (Rennes University Hospital, France) between November 2017 and October 2019.These patients underwent tests before and after heating at two visits spaced 10 days apart. DOAD was diagnosed on the basis of post-warming skin blood flow of ≤206 arbitrary units measured by laser Doppler flowmetry, contingent on previous results validated by arteriography as a gold standard. An interday kappa coefficient with a 95% confidence interval was used to assess reproducibility. RESULTS: Sixteen [10 females; mean age: 63 (9) years] SSc patients were included. Mean time interval between visits was 9 (5) days. The best FSBP threshold for DOAD diagnosis was 76 mmHg and DBI was 0.74 after warming. FSBP and DBI sensitivity/specificity were 59.1% (95% CI: 49.6, 68.5%)/92.5% (95% CI: 85.3, 99.6%) and 73.3% (95% CI: 64.9, 81.8%)/83.0% (95% CI: 72.9, 93.1%), respectively. Intra/interday reproducibility ranged from fair to good. CONCLUSION: The conclusions drawn from this study suggest that FSBP ≤ 76 mmHg and DBI ≤ 0.74 thresholds are potentially reliable indicators of DOAD and demonstrate fair to good intra- and interday reproducibility. TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT03264820.

Combination of Exercise Testing Criteria to Diagnose Lower Extremity Peripheral Artery Disease.

Objectives: Nothing is known about the interest of the combination of exercise tests to diagnose Lower-extremity Peripheral Artery Disease (LEPAD). The aim of this study was to assess if combining exercise testing criteria [post-exercise Ankle-Brachial Index (ABI) + exercise-oximetry (exercise-TcPO2)] improves the detection of lower limbs arterial stenoses as compared with post-exercise ABI using American Heart Association (AHA) criteria, or exercise-TcPO2 alone. Material and Methods: In a prospective monocentric study, consecutive patients with exertional-limb pain and normal resting-ABI referred to our vascular center (Rennes, France) were assessed from May 2016 to February 2018. All included patients had a computed tomography angiography (CTA), a resting-ABI, a post-exercise ABI and an exercise-TcPO2. AHA post-exercise criteria, new validated post-exercise criteria (post-exercise ABI decrease ≥18.5%, post-exercise ABI decrease <0.90), and Delta from Rest of Oxygen Pressure (Total-DROP) ≤-15mmHg (criterion for exercise-TcPO2) were used to diagnose arterial stenoses ≥50%. For the different combinations of exercise testing criteria, sensitivity or specificity or accuracies were compared with McNemar's test. Results: Fifty-six patients (mean age 62 ± 11 years old and 84% men) were included. The sensitivity of the combination of exercise testing criteria (post-exercise ABI decrease ≥18.5%, or post-exercise ABI decrease <0.90 or a Total-DROP ≤-15mmHg) was significantly higher (sensitivity = 81% [95% CI, 71-92]) than using only one exercise test (post-exercise AHA criteria (sensitivity = 57% [43-70]) or exercise-TcPO2 alone (sensitivity = 59% [45-72]). Conclusions: Combination of post-exercise ABI with Exercise-TcPO2 criteria shows better sensitivity to diagnose arterial stenoses compared with the AHA post-exercise criteria alone or Exercise-TcPO2 criteria used alone. A trend of a better accuracy of this combined strategy was observed but an external validation should be performed to confirm this diagnostic strategy.

Patient Characteristics and Preferences Regarding Anticoagulant Treatment in Venous Thromboembolic Disease.

Background: Anticoagulants are the recommended treatment for venous thromboembolic disease (VTE). The mode of anticoagulant administration may influence compliance, and therefore the effectiveness of the treatment. Unlike in atrial fibrillation or cancer-associated thrombosis, there is only limited data on patient preferences regarding the choice of anticoagulation in VTE. This study aims to evaluate patient preferences regarding anticoagulants in terms of administration: types (oral or injectable treatment) and number of doses or injections per day. Patients and Methods: This is a national survey through a questionnaire sent by e-mail to 1936 French vascular physicians between February and April 2019. They recorded the responses for each patient admitted for VTE. Results: Three hundred and eleven (response rate of 16%) of the 1936 contacted physicians responded for 364 patients. Among these, there were 167 fully completed questionnaires. Most patients (63%) express concerns about VTE and prefer oral treatment (81.5%), justified by the ease of administration (74%) and a fear of the injections (22%). When patients were taking more than three oral treatments they statistically chose injectable treatment more often (54%) than oral treatment (25%, p = 0.002). Patients who chose injectable treatment were also older (70 ± 16 vs. 58 ± 17 years old, p = 0.001). There was no statistically difference in anticoagulation preference according to gender or to the expected duration of treatment (6 weeks, 3 months, 6 months or unlimited). When oral treatment was preferred (81%), most chose oral treatment without dose adjustment and biomonitoring (74.3%). Among them, very few (5.8%) preferred a twice-daily intake. Conclusion: Patient preference in terms of anticoagulant treatment in VTE disease is in favor of oral treatment without adjustment or biomonitoring and with once-daily intake. When an injectable treatment is chosen, a prolonged duration of treatment does not seem to be a constraint for the patient. Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT03889457].

Inter-rater Reliability of a 13-Category Arterial Doppler Waveform Classification and Practice of French Vascular Physicians.

Background: Arterial Doppler Ultrasound waveform (DW) analysis allows the detection and evaluation of lower extremity peripheral artery disease. The high heterogeneity of the reported description of DW is reduced by the use of classification. However, the reliability of these classifications is either unknown or low to moderate and practices of vascular caregivers regarding the use of these classifications remain unknown. Aims: This study aims to assess the inter-observer reliability of the Saint-Bonnet classification, a 13-category DW classification. The secondary objective was to determine the utilization rate of the most common classifications and the ability of these classifications to describe DW. Methods: A national survey was conducted among all vascular physicians of French society of vascular medicine. They were invited by email to describe on a website 20 DW without and with the display of the Saint-Bonnet classification. The reliability of this classification was estimated by Fleiss' Kappa expressed with [95% confidence interval]. A semantic analysis allowed us to classify the physicians' responses according to the terms used. Finally we have evaluated for each classification the rate of misuse, i.e., the addition of a complementary term to the defined categories. Results: One hundred and ten physicians participated and only 5% of these were familiar with Saint-Bonnet classification. Fifty-four percent of vascular physicians used no classification at all. Vascular physicians used the Spronk (four-category), Descotes (five-category) and Saint-Bonnet (13-category) classifications for respectively, 31, 10, and 5%. Kappa coefficient of Fleiss (κ) was 0.546 [0.544-0.547] (p < 0.001). Reliability by category ranges from κ of 0.075 to 0.864. In multivariate analysis, the use of a classification was associated with fewer years of experience and was dependent on geographic location. Misuse rate by classification was 88, 82, and 5% using Spronk, Descotes and Saint-Bonnet classifications respectively. Conclusion: The reliability of Saint-Bonnet classification is weak to moderate by vascular physicians who are not familiar with its use. However, unlike the other classifications, it seems to be sufficiently precise so that the user does not need to complete its description. There is a significant heterogeneity in the use of arterial Doppler classifications in France.

Comparison of the Use of Arterial Doppler Waveform Classifications in Clinical Routine to Describe Lower Limb Flow.

BACKGROUND: Characterisation of arterial Doppler waveforms is a persistent problem and a source of confusion in clinical practice. Classifications have been proposed to address the problem but their efficacy in clinical practice is unknown. The aim of the present study was to compare the efficacy of the categorisation rate of Descotes and Cathignol, Spronk et al. and the simplified Saint-Bonnet classifications. METHODS: This is a multicentre prospective study where 130 patients attending a vascular arterial ultrasound were enrolled and Doppler waveform acquisition was performed at the common femoral, the popliteal, and the distal arteries at both sides. Experienced vascular specialists categorized these waveforms according to the three classifications. RESULTS: of 1033 Doppler waveforms, 793 (76.8%), 943 (91.3%) and 1014 (98.2%) waveforms could be categorized using Descotes and Cathignol, Spronk et al. and the simplified Saint-Bonnet classifications, respectively. Differences in categorisation between classifications were significant (Chi squared test, p < 0.0001). Of 19 waveforms uncategorized using the simplified Saint-Bonnet classification, 58% and 84% were not categorized using the Spronk et al. and Descotes and Cathignol classifications, respectively. CONCLUSIONS: The results of the present study suggest that the simplified Saint-Bonnet classification provides a superior categorisation rate when compared with Spronk et al. and Descotes and Cathignol classifications.

Immunometabolism at the cornerstone of inflammaging, immunosenescence, and autoimmunity in COVID-19.

Inflammaging constitutes the common factor for comorbidities predisposing to severe COVID-19. Inflammaging leads to T-cell senescence, and immunosenescence is linked to autoimmune manifestations in COVID-19. As in SLE, metabolic dysregulation occurs in T-cells. Targeting this T-cell dysfunction opens the field for new therapeutic strategies to prevent severe COVID-19. Immunometabolism-mediated approaches such as rapamycin, metformin and dimethyl fumarate, may optimize COVID-19 treatment of the elderly and patients at risk for severe disease.

Assessment of Inflammation and Calcification in Pseudoxanthoma Elasticum Arteries and Skin with 18F-FluroDeoxyGlucose and 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography Imaging: The GOCAPXE Trial.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease characterized by elastic fiber fragmentation and ectopic calcification. There is growing evidence that vascular calcification is associated with inflammatory status and is enhanced by inflammatory cytokines. Since PXE has never been considered as an inflammatory condition, no incidence of chronic inflammation leading to calcification in PXE has been reported and should be investigated. In atherosclerosis and aortic stenosis, positron emission tomography combined with computed tomographic (PET-CT) imaging has demonstrated a correlation between inflammation and calcification. The purpose of this study was to assess skin/artery inflammation and calcification in PXE patients. Methods: 18F-FluroDeoxyGlucose (18F-FDG) and 18F-Sodium Fluoride (18F-NaF) PET-CT, CT-imaging and Pulse wave velocity (PWV) were used to determine skin/vascular inflammation, tissue calcification, arterial calcium score (CS) and stiffness, respectively. In addition, inorganic pyrophosphate, high-sensitive C-reactive protein and cytokines plasma levels were monitored. RESULTS: In 23 PXE patients, assessment of inflammation revealed significant 18F-FDG uptake in diseased skin areas contrary to normal regions, and exclusively in the proximal aorta contrary to the popliteal arteries. There was no correlation between 18F-FDG uptake and PWV in the aortic wall. Assessment of calcification demonstrated significant 18F-NaF uptake in diseased skin regions and in the proximal aorta and femoral arteries. 18F-NaF wall uptake correlated with CS in the femoral arteries, and aortic wall PWV. Multivariate analysis indicated that aortic wall 18F-NaF uptake is associated with diastolic blood pressure. There was no significant correlation between 18F-FDG and 18F-NaF uptake in any of the artery walls. CONCLUSION: In the present cross-sectional study, inflammation and calcification were not correlated. PXE would appear to more closely resemble a chronic disease model of ectopic calcification than an inflammatory condition. To assess early ectopic calcification in PXE patients, 18F-NaF-PET-CT may be more relevant than CT imaging. It potentially constitutes a biomarker for disease-modifying anti-calcifying drug assessment in PXE.

A systematic review of lower extremity electrical stimulation for treatment of walking impairment in peripheral artery disease.

Lower extremity peripheral artery disease (PAD) induces an ischemic pain in the lower limbs and leads to walking impairment. Electrical stimulation has been used in patients with PAD, but no systematic review has been proposed to address the efficacy of the technique as a treatment for walking impairment in PAD. A systematic search was performed to identify trials focused on electrical stimulation for the treatment of walking impairment in patients with PAD in the Cochrane Central Register, PubMed, Embase, and the Web of Science. Studies were included where the primary outcomes were pain-free walking distance and/or maximal walking distance. When appropriate, eligible studies were independently assessed for quality using the Cochrane Collaboration's tool for assessing risk of bias. Five studies eligible for inclusion were identified, of which only two were randomized controlled studies. Trial heterogeneity prevented the use of the GRADE system and the implementation of a meta-analysis. Three types of electrical stimulation have been used: neuromuscular electrical stimulation (NMES, n = 3), transcutaneous electrical stimulation (n = 1), and functional electrical stimulation (n = 1). The two available randomized controlled studies reported a significant improvement in maximal walking distance (+40 m/+34% and +39 m/+35%, respectively) following a program of NMES. Owing to the low number of eligible studies, small sample size, and the risk of bias, no clear clinical indication can be drawn regarding the efficacy of electrical stimulation for the management of impaired walking function in patients with PAD. Future high-quality studies are required to define objectively the effect of electrical stimulation on walking capacity.

Evidence of Cardiovascular Calcification and Fibrosis in Pseudoxanthoma Elasticum Mouse Models Subjected to DOCA-Salt Hypertension.

Pseudoxanthoma Elasticum (PXE) is a rare disorder characterized by fragmentation and progressive calcification of elastic fibres in connective tissues. Although arterial hypertension (AHT) has been reported in PXE patients, its impact on pathological manifestations has as yet been unexplored. We investigated the consequences of experimental AHT on Abcc6-/- PXE mouse models. Experimental AHT was induced by deoxycorticosterone acetate (DOCA-salt) in uni-nephrectomised mice. Blood pressure (BP) and vascular reactivity were monitored using tail-cuff plethysmography and myography respectively. Calcium content and fibrosis were assessed using colorimetry, Von Kossa and Sirius red staining respectively. The gene expression implicated in vascular biology was measured using quantitative polymerase chain reaction. DOCA-salt induced a matching rise in BP in Abcc6-/- and WT mice. Aortic ring contraction and relaxation in vitro were comparable. Calcium accumulated in the hearts of hypertensive Abcc6-/- mice along with significant fibrosis in the myocardium and aorta by contrast with the WT mice. In hypertensive Abcc6-/- mouse aortas, these results were corroborated by gene expression patterns favouring calcification, fibrosis and extracellular matrix remodelling. Abcc6 loss-of-function is associated with greater cardiovascular calcification and fibrosis in mice subjected to DOCA-Salt hypertension. These results suggest likely cardiovascular deterioration in PXE patients with AHT, necessitating diligent BP monitoring.