Update About the Management of Low-Density Lipoprotein Cholesterol and Hypertriglyceridemia in Lower Extremity Peripheral Artery Disease Patients: Consensus of the French Society of Vascular Medicine and the French Society for Vascular and Endovascular Surgery.

BACKGROUND: A French intersociety consensus on behalf the Société Française de Médecine Vasculaire and the Société de Chirurgie Vasculaire et Endovasculaire was proposed in 2021 for the management of patients with lower extremity peripheral artery disease (LEAD). Recent studies have been published and an update of this consensus about the management of low-density lipoprotein cholesterol (LDLc) and hypertriglyceridemia was required. METHODS: A steering committee of 12 vascular physicians and surgeons defined questions of interest about LDLc and hypertriglyceridemia management. A French expert panel voted the proposals. Consensus was considered to have been achieved if more than 80% of the responses corresponded to either "Agreement" or "Disagreement". RESULTS: Among the 56 experts who were asked to participate, 46 (82%) accepted. After the first round of the Delphi procedure, the 4 proposals reached consensus. The following suggestions and recommendations were approved: 1. For LEAD patients treated by the highest tolerated statin dose ± ezetimibe and who have an LDLc ≥0.70 g/L, we recommend adding a proprotein convertase subtilisin/kexin type 9 inhibitor. 2. For LEAD patients treated by statin and who have elevated triglyceride level between ≥150 mg/dL and ≤500 mg/dL, we suggest adding Icosapent Ethyl. 3. Before adding Icosapent Ethyl in LEAD patients treated with statin, we suggest looking for symptoms that may suggest atrial fibrillation. 4. For LEAD patients treated by Icosapent Ethyl and who have symptoms that suggest atrial fibrillation, we recommend performing an electrocardiogram. CONCLUSIONS: This update will help clinicians to improve LEAD patient management.

Impact of wearable device-based interventions with feedback for increasing daily walking activity and physical capacities in cardiovascular patients: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To systematically review randomised controlled trials (RCTs) using a wearable physical activity monitoring device as an intervention to increase daily walking activity and improve physical capacities in patients with cardiovascular disease (CVD). DESIGN: Systematic review and meta-analysis of RCTs. DATA SOURCES: PubMed, Embase and Web of Science from inception to June 2022. ELIGIBILITY CRITERIA: Randomised controlled studies including patients with CVD over 18 years of age at the end of a cardiac rehabilitation programme comparing an intervention group using a wearable physical activity monitoring device with feedback with usual care or with a control group receiving no feedback on their physical activity and reporting a change in the daily number of steps and/or a change in the distance covered in the 6-minute walk test (6-MWT) or a change in peak oxygen uptake (V̇O2peak) as endpoints. RESULTS: Sixteen RCTs were included. The intervention of wearing a physical activity monitoring device with feedback significantly improved daily number of steps compared with controls (standardised mean difference (SMD) 0.85; 95% CI (0.42; 1.27); p<0.01). The effect was greater when the duration of the intervention was less than 3 months (SMD 1.0; 95% CI (0.18; 1.82); p<0.01) than when the duration of the intervention was 3 months or longer (SMD 0.71; 95% CI (0.27; 1.16); p<0.01), but no significant interaction was found between subgroups (p=0.55). 6-MWT distance and V̇O2peak showed only small effects (SMD 0.34; 95% CI (-0.11; 0.80); p=0.02 and SMD 0.54; 95% CI (0.03; 1.03); p=0.07, respectively). CONCLUSION: The use of wearable physical activity monitoring devices appears to help patients with CVD to increase their daily walking activity and thus their physical activity, particularly in the short term. PROSPERO REGISTRATION NUMBER: CRD42022300423.

Update on the thoracic outlet syndrome and plexus brachial syndrome: Specific clinical examination (for all) and rehabilitation protocol.

The diagnosis of uncomplicated forms of thoracobrachial outlet syndrome (TOS) and brachial plexus stretching syndrome (BPSS) is imprecise due to the lack of clear differentiation between dynamic vascular or neurological compression and brachial plexus stretching without vascular compression. After a review of literature, we propose and describe a simple way for clinical assessment of TOS, BPSS or association of both comprising 1 clinical sign and 2 manoeuvres. This clinical assessment can be performed by the medical doctor, the physiotherapist and the surgeon. The clinical diagnosis is essential because it will dictate the rehabilitation treatment. We propose and describe also a rehabilitation protocol comprising 10 phases with modulation of exercises according to clinical form (TOS, BPSS or association) and/or severity of symptoms. The physiotherapist has a capital role and is the guarantor of the effectiveness of the medical treatment. In France, a training is now available thanks to personal continuous development for diagnosis and treatment of TOS and BPSS. This is essential in order to propose an optimal care to patients.

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.

Management of superficial venous thrombosis in unevaluated situations: Cancer, severe renal impairment, pregnancy and post-partum.

BACKGROUND: Information is lacking as to the management of patients with superficial venous thrombosis (SVT) whose profile has been excluded from trials, such as patients with active cancer, severe renal impairment, or pregnancy. OBJECTIVES: To describe the frequency and management of SVT occurring in these situations. METHODS: We retrospectively analyzed the frequency, management and evolution of all patients with isolated SVT associated with either active cancer, severe renal impairment, or pregnant or postpartum women, diagnosed in 2 university hospital between January 1st, 2015 and December 31st, 2016. RESULTS: Of the 594 isolated SVTs individualized from the 7941 reports screened, 149 SVTs (105 in the upper extremity, 44 in the lower extremity) were analyzed: 94 (63%) associated with active cancer, 27 (18%) with severe renal impairment and 30 (20%) pregnant or postpartum women. SVT was treated with anticoagulant in 34 (36%) patients with cancer, 3 (11%) patients with severe renal impairment and 19 (63%) pregnant or postpartum women. At 3-month, 16 patients (10.8%) had a further venous thromboembolic event, 8 (5.4%) major bleeding, and 9 (6.1%) died. CONCLUSION: SVT in patients with active cancer, severe renal impairment and pregnant or postpartum women represents a quarter of isolated SVTs diagnosed. Heterogeneity of treatment patterns mainly affects patients with cancer and severe renal impairment. Poor outcomes, although probably linked to morbidity, call for dedicated research in these specific situations.

Disparities Between International Guidelines (AHA/ESC/ESVS/ESVM/SVS) Concerning Lower Extremity Arterial Disease: Consensus of the French Society of Vascular Medicine (SFMV) and the French Society for Vascular and Endovascular Surgery (SCVE).

Several international guidelines concerning lower extremity arterial disease (LEAD) have been published recently, in particular, by the American Heart Association the European Society of Cardiology/European Society for Vascular Surgery, the European Society for Vascular Medicine and the Society for Vascular Surgery. These guidelines differ in some respects and certain issues are not addressed. The objective of this consensus driven by the French Societies of vascular Medicine and surgery was to analyze the disparities between the different guidelines, as well as certain issues not covered, and develop proposals with regard to these points. The following fields of LEAD have been explored: 1) classifications, 2) clinical evaluation, 3) diagnostic criteria, 4) quantification of arterial stenosis using duplex ultrasound, 5) detection of asymptomatic multisite lesions, 6) screening for LEAD in the context of cardiac disease, 7) medical treatment, 8) supervised exercise therapy, 9) revascularization and revascularization of the internal artery stenosis, 10) management of chronic limb ischemia, 11) longitudinal follow-up, and 12) diet.

High tolerance of progressive elastic compression in peripheral arterial disease.

Background: Theoretically progressive compression stockings, which produce a higher compression at the calf than at the ankle level, improve venous return flow without exacerbating peripheral arterial insufficiency (PAD). We aimed to evaluate the short-term tolerance of elastic progressive compression stockings on peripheral arterial vascularisation in patients with symptomatic PAD and associated mild venous insufficiency. Patients and methods: Monocentric, prospective, open pilot study of 18 patients (acceptability study, 6 x 6 plan) evaluating the short-term tolerance of progressive compression stockings (18 ± 2 mmHg at calf and 8 ± 2 mmHg at ankle level) in patients with PAD (ankle brachial index ABI > 0.60 < 0.75) and chronic venous insufficiency (C1s-C4 stages of the CEAP classification). Day 15 tolerance was evaluated by a composite primary criteria comprising: no decrease > 15 % of ABI on each side, no decrease > 15 % of toe brachial index (TBI) on each side and no decrease > 25 % of the number of active plantar flexions performed while standing. Results: The proportion of men was 77.8 %, mean age was 77.3 ± 7.5 years and no patient were diabetic. At inclusion, the mean low ABI was 0.60 ± 0.04 and the mean high ABI was 0.77 ± 0.18. The mean low TBI was 0.32 ± 0.09 and the mean high TBI 0.46 ± 0.15. The mean number of active standing plantar flexions was 33.0 ± 5.0. The majority of the patients were classified in CEAP C2s and C3 classes (class 2: 16.7 %, class C2s: 27.8 %, class C3: 44.4 %, class C4: 5.6 % and class C4s: 5.6 %). Poor tolerance occurred in no patient. By day 30, no patient had worsening of their arterial and venous symptoms. No adverse events occurred during the study. Conclusions: These results suggest a high tolerance of progressive elastic stockings (18 ± 2 mmHg at calf and 8 ± 2 mmHg at ankle level) in symptomatic PAD.

Correlation between capillaroscopic classifications and severity in systemic sclerosis: results from SCLEROCAP study at inclusion.

OBJECTIVES: We assessed the correlation between severity of systemic sclerosis (SSc) and current staging systems based on nailfold capillaroscopy. METHODS: SCLEROCAP is a multicenter prospective study including consecutive scleroderma patients who have a yearly routine follow-up with capillaroscopy and digital blood pressure measurement. Capillaroscopy images were read by two observers blinded from each other, then by a third one in the case of discordance. A follow-up of 3 years is planned. The present study assessed the correlation between severity of systemic sclerosis (SSc) and current staging systems based on nail fold capillaroscopy at enrollment in the SCLEROCAP study. Univariate and multivariate logistic regression analysis was performed for both the Maricq and Cutolo classifications. RESULTS: SCLEROCAP included 387 patients in one year. Maricq's active and Cutolo's late classifications were very similar. In multivariate analysis, the number of digital ulcers (OR for 2 ulcers or more, respectively 2.023 [1.074-3.81] and 2.596 [1.434-4.699]) and Rodnan's skin score >15 (OR respectively 32.007 [6.457-158.658] and 18.390 [5.380-62.865]) correlated with Maricq's active and Cutolo's late stages. Haemoglobin rate correlated with Cutolo's late stage (hemoglobin<100 vs. >120 g/dl: OR 0.223 [0.051-0.980]), and total lung capacity with Maricq's active one: increase in 10%: OR0.833 [0.717-0.969]. CONCLUSIONS: The correlations found between capillaroscopy and severity of SSc are promising before the ongoing prospective study definitively assesses whether capillaroscopy staging predicts complications of SSc. Only two capillaroscopic patterns seem useful: one involving many giant capillaries and haemorrhages and the other with severe capillary loss.

Fibromuscular Dysplasia and Its Neurologic Manifestations: A Systematic Review.

Importance: Data on neurologic manifestations of fibromuscular dysplasia (FMD) are rare, and current knowledge remains limited. Objectives: To present a comprehensive review of the epidemiologic characteristics, management, and prognosis of the neurologic manifestations associated with cerebrovascular FMD (ie, involving cervical or intracranial arteries) and to guide future research priorities. Evidence Review: References were identified through searches of PubMed from inception to December 2017 using both the medical subject headings and text words. Additional sources were also identified by reviewing reference lists of relevant articles and through searches of the authors' personal files. Selected articles described at least 1 clinical or radiologic feature and/or outcome of cerebrovascular FMD. Isolated case reports could be included if they described interesting or noteworthy manifestations of FMD. Findings: A total of 84 relevant references were identified. Diagnosis of cerebrovascular FMD is based on the appearance of alternating arterial dilatation and constriction ("string of beads") or of focal narrowing, with no sign of atherosclerotic or inflammatory lesions. Although the diagnosis is easily apparent on results of radiographic imaging, making a diagnosis can be challenging in children or individuals with atypical phenotypes, such as purely intracranial FMD and arterial diaphragm. Involvement of multiple arteries is common, and there is increased incidence of cervical artery dissection and intracranial aneurysms. A variant in the PHACTR1 gene has been associated with FMD as well as cervical artery dissection and migraine, although less than 5% of cases of FMD are familial. Headaches, mainly of the migraine type, are observed in up to 70% of patients with FMD. Cerebrovascular FMD is mostly asymptomatic, but the most frequent neurologic manifestations include transient ischemic attack and ischemic stroke, notably in the presence of associated cervical artery dissection. Other conditions associated with FMD include subarachnoid hemorrhage and, rarely, intracranial hemorrhage. Management relies on observational data and expert opinion. Antiplatelet therapy is considered reasonable to prevent thromboembolic complications. Endovascular therapy is typically restricted to cases with symptomatic stenosis despite optimal medical therapy or in those with rupture of an intracranial aneurysm. Conclusions and Relevance: Longitudinal cohort studies of individuals of multiple ethnicities with biosampling are needed to better understand the risk factors, pathophysiological features, and outcomes of FMD. Patient advocacy groups could assist researchers in answering patient-centered questions regarding FMD.

Reproducibility of capillaroscopic classifications of systemic sclerosis: results from the SCLEROCAP study.

Objectives: Subgroups of capillaroscopic scleroderma landscape have been correlated with stages of SSc: two groups for Maricq's classification (slow and active), and three for Cutolo's classification (early, active and late). We report inter- and intra-observer agreement for these classifications as a preliminary step in the multicentre prospective SCLEROCAP study, which aims to assess the classification and single capillaroscopic items as prognostic tools for SSc. Methods: SCLEROCAP included 385 patients. Agreement was studied in the first 100 patients, who were independently rated twice by two observers, blind to patients' characteristics; 30 of the patients were rated once by six observers. After consensus meetings, these ratings were held again. Kappa and intraclass correlation coefficients were used to assess agreement. Results: Interobserver agreement on 100 patients was moderate for Maricq and Cutolo classifications [κ 0.47 (0.28, 0.66) and 0.49 (0.33, 0.65), respectively], and became substantial after consensus meetings [0.64 (0.50, 0.77) and 0.69 (0.56, 0.81)]. Intra-observer agreement between two observers was moderate to substantial: κ 0.54 (0.33, 0.75) and 0.70 (0.57, 0.83) for Maricq's classification; 0.57 (0.38, 0.77) and 0.76 (0.65, 0.87) for Cutolo's. Thirty patients were rated once by each of six observers, and agreement was moderate to substantial: κ 0.57 ± 0.10 (Maricq) and 0.61 ± 0.12 (Cutolo). Agreement was substantial for bushy, giant capillaries and microhaemorrhages, moderate for capillary density and low for oedema, disorganization and avascular areas. Conclusion: The moderate reproducibility of Maricq and Cutolo classifications might hamper their prognostic value in SSc patients. Consensus meetings improve reliability, a prerequisite for better prognostic performances. A focus on giant capillaries, haemorrhages and capillary density might be more reliable.

Reproducibility of the scleroderma pattern assessed by wide-field capillaroscopy in subjects suffering from Raynaud's phenomenon.

Objectives: The aim of this work was to study inter- and intra-observer agreement for the diagnosis of scleroderma pattern by wide-field capillaroscopy. Methods: Images were taken from 50 patients known to have SSc and 50 controls consulting for RP who did not have SSc. These images were rated simultaneously by 11 experienced vascular medicine physicians as scleroderma pattern or not. Two weeks later, 7 of the 11 observers again rated the same images. Results: Inter-observer agreement was almost perfect between the 11 observers (κ 0.86 ± 0.01), and the proportion of concordant observations was 79% (70-87). When each observer was compared with the reference, agreement was also almost perfect: κ coefficient 0.92 ± 0.03 and proportion of concordant observations 79% (70-87). Intra-observer agreement was also almost perfect: median κ coefficient 0.94 (0.78-0.96) and median proportion of concordant observations 97% (89-98). Conclusion: Excellent inter- and intra-observer agreement was obtained in experienced vascular physicians for the diagnosis of capillaroscopic landscape by wide-field nailfold capillary microscopy.

High Prevalence of Multiple Arterial Bed Lesions in Patients With Fibromuscular Dysplasia: The ARCADIA Registry (Assessment of Renal and Cervical Artery Dysplasia).

Fibromuscular dysplasia (FMD) commonly affects the renal and cervical arteries but has been described to affect other vascular beds as well. The prevalence of and clinical characteristics associated with multisite FMD (string-of-beds or focal stenoses affecting at least 2 vascular beds) are not known. In the prospective ARCADIA registry (Assessment of Renal and Cervical Artery Dysplasia), symptomatic patients with renal artery (RA) FMD underwent tomographic- or magnetic resonance-angiography from the aortic arch to the intracranial arteries and those with cervical FMD from the diaphragm to the pelvis. Of 469 patients (84.0% women), 225 (48.0%) had multisite FMD. In addition, 86 of 244 patients with single-site disease had dissections or aneurisms affecting other vascular beds, totaling 311 patients (66.3%) with lesions in >1 vascular bed. Among patients with a cerebrovascular presentation, the prevalence of RA lesions was higher in patients with than in those without hypertension (odds ratio, 3.4; 95% confidence interval, 1.99-6.15). Among patients with a renal presentation, the prevalence of cervical lesions was higher in patients with bilateral than in those with unilateral RA lesions (odds ratio, 1.9; 95% confidence interval, 0.99-3.57). In conclusion, FMD is a systemic arterial disease. At least 2 vascular beds were affected by dysplastic stenoses in 48.0% of cases and by dysplastic stenoses, aneurysms, and dissections in 66.1% of cases. RA imaging should be proposed to hypertensive patients with a cerebrovascular presentation. Cervical artery imaging should be considered in patients with a renal presentation and bilateral RA lesions. CLINICAL TRIAL REGISTRATION: URL: www.Clinicaltrials.gov. Unique identifier: NCT02884141.

Statement for Doppler waveforms analysis.

Peripheral artery disease of the lower limbs (PAD) is a common disease. Evaluation of PAD is primarily based on non-invasive examinations with analysis of the arterial Doppler signal being a key element. However, the description of arterial Doppler waveforms morphologies varies considerably across medical schools and from country to country. In order to overcome this issue, the French College of Teachers for Vascular Medicine (Collège des Enseignants de Médecine Vasculaire; CEMV) has summarised the published data on Doppler waveforms analysis and proposes a new "Saint-Bonnet" classification system to describe Doppler waveforms morphologies. The simplified Saint-Bonnet classification comprises eight types and allows taking into account if the Doppler signal does not revert to baseline. This classification, which is based on previous classifications, could improve the descriptions of both physiological and pathological waveforms, recorded in lower limb arteries. According to the reviewed literature, recommendations about the use of Doppler waveforms are proposed. This statement is a preamble to reach an international consensus on the subject, which would standardize the description of arterial waveforms and improve the management of PAD patients.

Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide.

OBJECTIVE: To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). METHODS: We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR) was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline. RESULTS: Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. CONCLUSION: This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.