Anemia, an independent predictive factor for amputation and mortality in patients hospitalized for peripheral artery disease.

OBJECTIVES: Anemia is associated with poorer outcome in coronary artery disease (CAD) and heart failure (HF), but data on patients with peripheral artery disease (PAD) are scarce, especially regarding the local (limb) prognosis. It was hypothesized that anemia is associated with poorer prognosis in patients hospitalized for PAD, and this relationship would be proportional to the severity of the anemia. DESIGN: Prospective cohort study. MATERIALS: The Cohorte des Patients Artéritiques (COPART) is a multicenter registry of patients hospitalized for PAD in three university hospitals in southwestern France. METHODS: Clinical and biological data were collected at entry. Patients were followed up to 1 year. Anemia was defined by Hb < 8.2 mmol/L in men and <7.6 mmol/L in women. The primary outcome was 1-year survival free from major amputation. The secondary outcome was 1-year major amputation. RESULTS: Data of 925 consecutive patients (70.7 ± 12.8 years, 29.2% females) were analyzed. Patients were hospitalized either for revascularization or medical therapy, with Rutherford categories 3 (25%), 4 (9.1%), 5 or 6 (55.1%) as well as acute limb ischemia (10.8%). Anemia was present in 471 patients (50.9%). These patients were significantly older, with higher rates of hypertension, diabetes, clinical CAD, HF, chronic kidney disease, and cancer, and with lower rates of smoking and dyslipidemia than their counterparts (p < .05 for all). In multivariate models, anemia was significantly and independently associated (p < 0.001) with death and amputation (HR 1.44; 95% CI 1.15-1.80) with similar findings for secondary outcomes. A lower level of hemoglobin is associated with a higher risk of mortality and amputation (HR 1.20; 95% CI 1.09-1.32). CONCLUSION: Anemia and its severity are independent predictors of mortality and limb loss in patients hospitalized for PAD.

Relationship between kalemia and intensive care unit admission or death in hospitalized COVID-19 patients: A cohort study.

BACKGROUND: SARS-CoV-2 uses Angiotensin-Converting Enzyme 2 as a viral gateway to the cell and could interact with the renin-angiotensin-aldosterone system. Other studies have shown kalemia abnormalities in patients with severe forms of coronavirus disease 2019. Our goal was to assess the prognosis value of kalemia within ten days of symptom offset in the COVID-19 hospitalized population. METHODS: We analyzed data from a prospective cohort that included 65 patients with COVID-19, admitted between March 15, 2020, and March 21, 2020. The study aimed at determining the relationship between baseline kalemia and the admission to an intensive care unit (ICU) or death. RESULTS: The median age of the patients was 65 [54-79] years old, and 66.2% of the patients were men. Baseline kalemia under 3.8mmol/l occurred in 31 patients (48%), including 11 patients (35.5%) who were admitted to an ICU and one patient (3.2%) who died before ICU admission. In the primary end-point analysis, the adjusted hazard ratios for admission to an ICU or death were 3.52 [95% confidence interval (CI), 1.12 to 11.04] among patients with low baseline kalemia. CONCLUSION: Our study suggests that low kalemia levels within ten days of the first symptom onset might be associated with an increased risk of intensive care unit admission or death. The future perspective should be to better understand this relationship.

Ergotism with acute limb ischemia, provoked by HIV protease inhibitors interaction with ergotamine, rescued by multisite transluminal balloon angioplasty.

Acute limb ischemia induced by arterial vasospasm remains an exceptional situation, favoured by the use of arterial vasoconstrictors. The risk of these substances is largely underestimated in the general population, especially with the co-administration of strong cytochrome inhibitors like human immunodeficiency virus (HIV) protease inhibitors. A 33-year-old woman, who used to take dihydroergotamine for orthostatic hypotension, was prescribed a post-exposure HIV prophylaxis including lopinavir and ritonavir. One day later, she presented an acute bilateral limb ischemia with a sudden pain in both calves, initially while walking and then at rest with bilateral ischemic toes. Angiography confirmed diffuse arterial vasospasm of the lower limb arteries. A first-line therapy with isosorbide dinitrate and amlodipine was ineffective, with rapid clinical worsening. A combination of intra-arterial injections and intra-venous infusions of vasodilators, transluminal balloon angioplasty and bilateral 4-Compartment fasciotomies permitted rapid improvement and finally resulted in both lower limbs rescue. This case and literature review illustrate ergotism due to ergotamine overdose after taking HIV protease inhibitors. It also demonstrates the benefit of an interventional procedure besides medical therapy with vasodilators in severe arterial vasospasm. All along the lower limb arterial tree, transluminal balloon angioplasty restored the blood flow, without vasospasm recurrence. CONCLUSION: In case of ergotism with acute lower limbs ischemia, combining medical vasodilator therapy with interventional procedure can restore the arterial blood flow, thus allowing to save lower limbs.

Management of cancer-related thrombosis in the era of direct oral anticoagulants: A comprehensive review of the 2019 ITAC-CME clinical practice guidelines. On behalf of the Groupe Francophone Thrombose et Cancer (GFTC).

Venous thromboembolism (VTE) is a common disease complication in cancer patients and the second cause of death after cancer progression. VTE management and prophylaxis are critical in cancer patients, but effective therapy can be challenging because these patients are at higher risk of VTE recurrence and bleeding under anticoagulant treatment. Numerous published studies report inconsistent implementation of existing evidence-based clinical practice guidelines (CPG), including underutilization of thromboprophylaxis, and wide variability in clinical practice patterns across different countries and various practitioners. This review aims to summarize the 2019 ITAC-CME evidence-based CPGs for treatment and prophylaxis of cancer-related VTE, which include recommendations on the use of direct oral anticoagulants specifically in cancer patients. The guidelines underscore the gravity of developing VTE in cancer and recommend the best approaches for treating and preventing cancer-associated VTE, while minimizing unnecessary or over-treatment. Greater adherence to the 2019 ITAC guidelines could substantially decrease the burden of VTE and improve survival of cancer patients.

4D simultaneous tissue and blood flow Doppler imaging: revisiting cardiac Doppler index with single heart beat 4D ultrafast echocardiography.

The goal of this study was to demonstrate the feasibility of semi-automatic evaluation of cardiac Doppler indices in a single heartbeat in human hearts by performing 4D ultrafast echocardiography with a dedicated sequence of 4D simultaneous tissue and blood flow Doppler imaging. 4D echocardiography has the potential to improve the quantification of major cardiac indices by providing more reproducible and less user dependent measurements such as the quantification of left ventricle (LV) volume. The evaluation of Doppler indices, however, did not benefit yet from 4D echocardiography because of limited volume rates achieved in conventional volumetric color Doppler imaging but also because spectral Doppler estimation is still restricted to a single location. High volume rate (5200 volume s-1) transthoracic simultaneous tissue and blood flow Doppler acquisitions of three human LV were performed using a 4D ultrafast echocardiography scanner prototype during a single heartbeat. 4D color flow, 4D tissue Doppler cineloops and spectral Doppler at each voxel were computed. LV outflow tract, mitral inflow and basal inferoseptal locations were automatically detected. Doppler indices were derived at these locations and were compared against clinical 2D echocardiography. Blood flow Doppler indices E (early filling), A (atrial filling), E/A ratio, S (systolic ejection) and cardiac output were assessed on the three volunteers. Simultaneous tissue Doppler indices e' (mitral annular velocity peak), a' (late velocity peak), e'/a' ratio, s' (systolic annular velocity peak), E/e' ratio were also estimated. Standard deviations on three independent acquisitions were averaged over the indices and was found to be inferior to 4% and 8.5% for Doppler flow and tissue Doppler indices, respectively. Comparison against clinical 2D echocardiography gave a p  value larger than 0.05 in average indicating no significant differences. 4D ultrafast echocardiography can quantify the major cardiac Doppler indices in a single heart beat acquisition.

Percutaneous Deep Venous Arterialization for Severe Critical Limb Ischemia in Patients With No Option of Revascularization: Early Experience From Two European Centers.

PURPOSE: To report our initial experience of fully percutaneous deep venous arterialization (pDVA) for the treatment of chronic critical limb ischemia (cCLI) after failed distal angioplasty. MATERIALS AND METHODS: pDVA was performed in five consecutive patients by creating an arteriovenous fistula (AVF) between a below the knee artery and its satellite deep vein. In this early experience, only patients with failed prior interventional attempts at establishing flow with no distal targets for an arterial bypass were selected. Early technical success was defined as successful AVF creation and retrograde venous perfusion of the wound site. Patient demographics, procedural details, morbidity/mortality and wound healing outcomes were assessed prospectively. Patients were followed up in wound care centers, and graft patency was documented on duplex ultrasound. RESULTS: All five consecutive patients (mean age 58 years) underwent successful pDVA without any procedural complications. There were neither 30-day major adverse limb events nor major cardiovascular complications. Three out of the five patients (60%) had clinical improvement as observed by resolution of rest pain and complete wound healing. At the 1-month FU, one patient died and one patient received a major amputation. The median wound healing time was 39 weeks. CONCLUSION: pDVA is a safe and feasible vascularization alternative in patients with end-stage/no-option CLI. The early experience highlights the need for a multidisciplinary approach including a dedicated wound care service.

Correction to: Percutaneous Deep Venous Arterialization for Severe Critical Limb Ischemia in Patients With No Option of Revascularization: Early Experience From Two European Centers.

The fifth author's name was incorrectly published as "M. Messas". The correct name is "E. Messas". The original article has been corrected.

[Gardner-Diamond syndrome in a young man: A case report and literature review]. / Syndrome de Gardner-Diamond : à propos d'un cas chez un homme jeune et revue de la littérature.

INTRODUCTION: Gardner-Diamond syndrome is a rare condition secondary to a sensitization to self-erythrocytes. It is predominantly seen in women and presents as a painful ecchymotic disorder. An underlying psychiatric disease or a triggering psychological stress is of important diagnostic value. CASE REPORT: We report a 24-year-old patient who presented with intermittent spontaneous painful ecchymosis since 5 years. Complementary investigations failed to identify an organic disorder. Gardner-Diamond syndrome was retained because of the clinical presentation, the negativity of diagnostic work-up and the identification of a psychological trauma. Patient management (pain, psychological support) is difficult, justifying a multidisciplinary approach. CONCLUSION: Gardner-Diamond syndrome is a rare and unrecognized disorder, which should be discussed in the presence of ecchymotic or purpuric lesions that do not have a diagnostic orientation. Early recognition of this disorder enables initiation of an appropriate management, but also limits unnecessary additional explorations.

[Recanalization procedure of the common femoral vein following iatrogenic femoral chronic occlusion: 3 cases]. / Recanalisation veineuse des membres inférieurs sur occlusion fémorale chronique iatrogène : à propos de 3 cas.

Common femoral vein occlusion (CFVO) is frequently found in patients with chronic venous insufficiency. The iatrogenic form, secondary to either central catheter or surgery, is very rare but highly symptomatic. Classical compression therapy barely improves the clinical status of these patients, making them suitable candidates for an interventional procedure for venous recanalization. METHODS: We report here three consecutive cases of iatrogenic CFVO referred to our outpatient clinic because the disease had an impact on daily life activities. We detail the recanalization procedure, the Doppler control and the short-term outcome. RESULTS: In each case, endovascular recanalization required rigid material (rigid guide or Colapinto needle) to cross the fibrous adhesions before angioplasty could be performed with stenting. The procedure required two attempts in each case, underlining its complexity, but eventually enabled effective recanalization. No major complication occurred per- or post-procedure. One month later, a duplex Doppler control confirmed the permeability of the common femoral vein. The patients had experienced rapid and significant symptom improvement. CONCLUSION: Patients suffering from severe chronic venous insufficiency caused by iatrogenic CFVO can benefit from endovascular recanalization. Although these procedures may be complex due to the extensive fibrosis at the Scarpa and require specialized equipment, no major complications were observed. Patency of the recanalization persisted at least one month after the procedure. Symptom relief was good.

Pulsed cavitational therapy using high-frequency ultrasound for the treatment of deep vein thrombosis in an in vitro model of human blood clot.

Post-thrombotic syndrome, a frequent complication of deep venous thrombosis, can be reduced with early vein recanalization. Pulsed cavitational therapy (PCT) using ultrasound is a recent non-invasive approach. We propose to test the efficacy and safety of high-frequency focused PCT for drug-free thrombolysis (thrombotripsy) in a realistic in vitro model of venous thrombosis. To reproduce venous thrombosis conditions, human whole blood was allowed to clot by stasis in silicone tubes (6 mm internal diameter) at a 30 cm H2O pressure, maintained during the whole experiment. We engineered an ultrasound device composed of dual 2.25 MHz transducers centered around a 6 MHz imaging probe. A therapeutic focus was generated at a 3.2 cm depth from the probe. Thrombotripsy was performed by longitudinally scanning the thrombus at three different speeds: 1 mm s-1 (n = 6); 2 mm s-1 (n = 6); 3 mm s-1 (n = 12). Restored outflow was measured every three passages. Filters were placed to evaluate the debris size. Twenty-four occlusive thrombi, of 2.5 cm mean length and 4.4 kPa mean stiffness, were studied. Flow restoration was systematically obtained by nine subsequent passages (4.5 min maximum). By varying the device's speed, we found an optimal speed of 1 mm s-1 to be efficient for effective recanalization with 90 s (three passages). Within 90 s, flow restoration was of 80, 62 and 74% at respectively 1, 2 and 3 mm s-1. For all groups, cavitation cloud drilled a 1.7 mm mean diameter channel throughout the clot. Debris analysis showed 92% of debris <10 µm, with no fragment > 200 µm.

[Takayasu arteritis]. / La maladie de Takayasu.

Takayasu arteritis is a chronic inflammatory vasculitis of unknown origin affecting large vessels, predominantly the aorta and its main branches. Vessel inflammation leads to wall thickening, fibrosis, and stenosis. The lesions are often asymptomatic leading to limb numbness, transient ischemic attack, cardiovascular event and renovascular hypertension. Treatment is based on corticosteroids, immunosuppressant and biologics if necessary. Endovascular treatment and open-surgery can be useful for end-organ ischemia relief.

[Management of deep-vein thrombosis: A 2015 update]. / Prise en charge de la thrombose veineuse profonde en 2015.

Deep vein thrombosis (DVT) is a frequent and multifactor disease, with two major complications, post thrombotic syndrome and pulmonary embolism. Both transient (surgery, plaster immobilization, bed rest/hospitalization) and chronic/persistent (age, cancer, clinical or biological thrombophilia…) risk factors modulate treatment duration. Diagnostic management relies on clinical evaluations, probability followed by laboratory tests or imaging. So far, compression ultrasound is the diagnostic test of choice to make a positive diagnosis of DVT. Anticoagulants at therapeutic dose for at least 3 months constitute the cornerstones of proximal (i.e. involving popliteal or more proximal veins) DVT therapeutic management. The arrival of new oral anticoagulants should optimize ambulatory management of DVT.

Biotherapies in large vessel vasculitis.

Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are large vessel vasculitis (LVV) and aortic involvement is not uncommon in Behcet's disease (BD) and relapsing polychondritis (RP). Glucocorticosteroids are the mainstay of therapy in LVV. However, a significant proportion of patients have glucocorticoid dependance, serious side effects or refractory disease to steroids and other immunosuppressive treatments such as cyclophosphamide, azathioprine, mycophenolate mofetil and methotrexate. Recent advances in the understanding of the pathogenesis have resulted in the use of biological agents in patients with LVV. Anti-tumor necrosis factor-α drugs seem effective in patients with refractory Takayasu arteritis and vascular BD but have failed to do so in giant cell arteritis. Preliminary reports on the use of the anti-IL6-receptor antibody (tocilizumab), in LVV have been encouraging. The development of new biologic targeted therapies will probably open a promising future for patients with LVV.

Intramyocardial transplantation of autologous myoblasts: can tissue processing be optimized?

BACKGROUND: Autologous skeletal myoblast (SM) transplantation improves function of infarcted myocardium, but pretransplantation cultures remain a complex process. This study assessed whether it could be optimized by muscle preconditioning with the local anesthetic bupivacaine or even bypassed with the use of the so-called mince technique. METHODS AND RESULTS: Muscle preconditioning consisted of intramuscular injections of the tibialis anterior of rats, 2 days before harvest. After 7 days of culture, the number of available myoblasts was significantly increased compared with nonconditioned controls (1 683 147 versus 85 300, P:=0.0013). The mince technique was then assessed. A myocardial infarction was created in 66 rats by coronary artery ligation. One week later, rats were reoperated on and intramyocardially injected with culture medium alone (controls, n=23), autologous cultured SM (3.5 x 10(6), n=21), or autologous muscle minced into a fine slurry, which was immediately transplanted (n=22). All muscles had been preconditioned. Left ventricular function was assessed by 2D echocardiography. Whereas end-diastolic volumes expanded over time in all groups, left ventricular ejection fraction (%, mean+/-SEM) was increased only in the cultured SM-transplanted group at 1 (P:=0. 0006) and 2 months (P:=0.0008) versus baseline (37.52+/-1.92 and 40. 92+/-2.17 versus 30.34+/-1.74), with a significant additional benefit between 1 and 2 months (P:=0.0069). CONCLUSIONS: Cell culture remains mandatory for SM transplantation to be successful but, in a clinical perspective, this process can be made more expeditious by preharvest muscle conditioning with bupivacaine, which greatly enhances the baseline cell yield.

Paradoxic decrease in ischemic mitral regurgitation with papillary muscle dysfunction: insights from three-dimensional and contrast echocardiography with strain rate measurement.

BACKGROUND: Ischemic mitral regurgitation (MR) was first ascribed to papillary muscle (PM) contractile dysfunction. Current theories include apical leaflet tethering caused by left ventricular (LV) distortion, but PM dysfunction is still postulated and commonly diagnosed. PM contraction, however, parallels apical tethering, suggesting the hypothesis that PM contractile dysfunction can actually diminish MR due to ischemic distortion of the inferior base alone. METHODS AND RESULTS: We therefore occluded the proximal circumflex circulation in 7 sheep while maintaining PM perfusion, confirmed by contrast echocardiography. By 3D echocardiography, we measured the tethering distance between the ischemic medial PM tip and anterior annulus and LV ejection volume to give MR (by subtracting flowmeter LV outflow). In 6 sheep without initial MR, inferior ischemia alone produced PM tip retraction with restricted leaflet closure and mild-to-moderate MR (regurgitant fraction, 25.2+/-2.8%). Adding PM ischemia consistently decreased MR and tethering distance (5.2+/-0.3 to 1.4+/-0.3 mL; +3.8+/-0.5 mm to -2.2+/-0.7 mm axially relative to baseline; P<0.001) as PM strain rate decreased from +0.78+/-0.07 per second (contraction) to -0.42+/-0.06 per second (elongation, P<0.001) and leaflet tenting decreased. In one sheep, prolapse and MR resolved with inferior ischemia and recurred with PM ischemia. CONCLUSIONS: PM contractile dysfunction can paradoxically decrease MR from inferobasal ischemia by reducing leaflet tethering to improve coaptation. This emphasizes the role of geometric factors in ischemic MR mechanism and potential therapy.

Chordal cutting: a new therapeutic approach for ischemic mitral regurgitation.

BACKGROUND: Mitral regurgitation (MR) conveys adverse prognosis in ischemic heart disease. Because such MR is related to increased leaflet tethering by displaced attachments to the papillary muscles (PMs), it is incompletely treated by annular reduction. We therefore addressed the hypothesis that such MR can be reduced by cutting a limited number of critically positioned chordae to the leaflet base that most restrict closure but are not required to prevent prolapse. This was tested in 8 mitral valves: a porcine in vitro pilot with PM displacement and 7 sheep with acute inferobasal infarcts studied in vivo with three-dimensional (3D) echo to quantify MR in relation to 3D valve geometry. METHODS AND RESULTS: In all 8 valves, PM displacement restricted leaflet closure, with anterior leaflet angulation at the basal chord insertion, and mild-to-moderate MR. Cutting the 2 central basal chordae reversed this without prolapse. In vivo, MR increased from 0.8+/-0.2 to 7.1+/-0.5 mL/beat after infarction and then decreased to 0.9+/-0.1 mL/beat with chordal cutting (P<0.0001); this paralleled changes in the 3D leaflet area required to cover the orifice as dictated by chordal tethering (r(2)=0.76). CONCLUSIONS: Cutting a minimum number of basal chordae can improve coaptation and reduce ischemic MR. Such an approach also suggests the potential for future minimally invasive implementation.

[Peripheral artery occlusive disease of the lower limbs: Rapid aggravation in a patient taking nilotinib for chronic myeloid leukemia]. / Artériopathie des membres inférieurs d'aggravation rapide chez un patient traité par nilotinib pour leucémie myéloïde chronique.

The development of tyrosine kinase inhibitors (TKI) has revolutionized management of patients with chronic myeloid leukemia (CML), transforming this fatal disease into a chronic disease with nearly normal life expectancy. Nilotinib is a second generation TKI targeting the oncoprotein BCR-ABL used in patients in the chronic phase of CML. Several research teams have suggested over recent years that nilotinib might be the causal agent in the development or aggravation of vascular disease, particularly in patients with cardiovascular risk factors or an established cardiovascular disease. We report here the case of a patient who developed severe peripheral arterial disease of the lower limbs that worsened despite optimal medical and surgical care, presenting recurrent re-stenoses after different revascularization techniques (bypass, angioplasty…) associated with aggravation of severe trophic disorders to the point of potentially requiring amputation. Discontinuation of nilotinib enabled a stabilization of the arterial lesions and complete healing of the trophic lesions. This case illustrates the importance of recognizing co-morbid conditions in patients with severe vascular disease and to examine the possibility of drug interactions leading to rapid aggravation of arterial disease with no other cause. Studying the pathophysiological impact of TKIs on the vascular system may open new avenues of research for the investigation of factors triggering arteriosclerosis.

[Management of venous thromboembolism: A 2015 update]. / Prise en charge de la maladie thromboembolique veineuse en 2015.

Deep venous thrombosis (DVT) and pulmonary embolism (PE) constitute venous thromboembolic disease (VTE). Venous thromboembolic disease is a common, serious, and multifactorial disease, the incidence of which increases with age. Risk factors, whether transient (surgery, plaster immobilization, bed rest/hospitalization) or chronic/persistent (age, cancer, clinical or biological thrombophilia, etc.), modulate the duration of treatment. In the absence of pathognomonic clinical sign or symptom, diagnostic management relies in the evaluation of the clinical pre-test probability followed by a laboratory or an imaging testing. So far, compression ultrasound and multidetector computed tomography angiography are the best diagnostic tests to make a positive diagnosis of DVT or PE, respectively. Anticoagulants at therapeutic dose for at least 3months constitute the cornerstone of VTE management. Availability of new direct oral anticoagulants, which have recently been shown to be as effective and as safe as vitamin K antagonist in clinical trials, should facilitate ambulatory management of VTE and favour extended treatments for individuals with unprovoked VTE or VTE provoked by a chronic/persistent risk factor.

[Distal revascularization in diabetic patients with chronic limb ischemia]. / La revascularisation distale des diabétiques en ischémie critique.

Diabetes mellitus is an independent risk factor for peripheral artery disease. Life expectancy is 41 months for diabetic patients with an ischemic ulcer. The characteristics of diabetic arteriopathy make its treatment more difficult than in non-diabetic patients. Few data are available about the surgical treatment of arteriopathy in diabetic patients (including angioplasty or bypass), especially in case of distal arteriopathy. The choice of the procedure depends on multiple factors such as the disease localization, its extent, distal blood flow and vascular disease-related surgical risk. The principal aim of revascularisation is to restore direct flow to the foot in order to ensure wound healing and limb salvage. With percutaneous endoluminal angioplasty, limb salvage can be achieved in more than 80% of patients at 1-3 years. The percutaneous procedure is less invasive than open surgery, there are fewer complications, and morbidity and mortality rates are reduced; moreover, a second procedure remains possible in the future. With bypass surgery, the rate of limb salvage exceeds 80% at five years. Nevertheless, peri-operative mortality reaches 3% and arterial anatomy, patient-related risks factors or venous graft availability may be limitations. New endovascular techniques especially designed for the distal arteries of the lower limbs enable very distal revascularization with morbidity and mortality rates lower than with surgery.