Amputation-free survival in the long-term follow-up and gender-related characteristics in patients revascularized for critical limb ischemia.

OBJECTIVE: Patients with Critical Limb Ischemia (CLI) present a high risk of cardiovascular events and death. Revascularization is the cornerstone of therapy to relieve ischemic pain and prevent limb loss. Literature data suggest that women tend to present with worse outcomes after revascularization. The aim of the present study is to determine amputation-free survival in a long-term follow-up in women and men following endovascular revascularization procedure for CLI. METHODS: From November 2013 to December 2020, 357 consecutive patients were retrospectively included. Clinical and biological parameters were recorded at baseline before endovascular revascularization. During follow-up until February 2023, overall survival and amputation-free survival (freedom from major amputation) were analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed to study the parameters associated with amputation-free survival. A P<0.05 was considered as statistically significant. RESULTS: A total of 357 consecutive patients were included, 189 men and 168 women with CLI, with a mean age of 78.6±12 years. Treated hypertension (79%), diabetes mellitus (48%), coronary artery disease (39%) and protein malnutrition (61%) were the most prevalent comorbidities. Women were older than men with a mean age of 82.4±11.4 years (versus 75.4±11 years in men) and presented more frequently with protein malnutrition (70% of women). Prevalence of diabetes, tobacco use and history of coronary heart disease were significantly higher in men. During the 10-year follow-up period, 241 patients had died (68%) and 38 (11%) underwent major amputation, of whom 22 patients were still alive on February 2023. Median survival was 35.5 months [IQR: 29.5; 43] in the overall population, 38.5 [32; 50.4] months in women and 33.5 months [24.7; 43.5] in men. No gender-related differences were noted according to peri-procedural complications, survival probability and amputation-free survival. In multivariate analysis for amputation-free survival, age, previous coronary heart disease, C-reactive protein level, left ventricular ejection fraction (LVEF)<60% and albumin level<35g/L were correlated with poor outcome. In particular, protein malnutrition, as a treatable risk factor, appears significantly correlated with poor outcome in both men and women (HR=2.50 [1.16;5.38], P=0.0196 in men; HR=1.77 [1.00;3.13], P=0.049 in women). CONCLUSION: The present results highlight that mortality in patients after endovascular revascularization remains high with a mortality rate of 28% at 1 year, 40% at 2 years and 51% at 3 years. Women represented a distinct population, almost 10-year older than their male counterparts, with more prevalent protein malnutrition. However, no gender-related difference was noted according to amputation-free survival on the long-term follow-up. Associated risk factors are mainly age, a history of coronary heart disease, pre-procedural inflammatory syndrome and protein malnutrition. Correction of malnutrition could have the potential to improve functional and general long-term prognosis in patients with CLI together with optimal medical and interventional management.

Evaluation of the ankle brachial index and toe brachial index for peripheral arterial disease diagnosis in patients over 70 years with lower limb ulcers.

OBJECTIVE: The aim of our study was to evaluate the diagnostic performance of the ankle brachial index using pulsed Doppler, and the toe brachial index using laser Doppler, in comparison with the arterial Doppler ultrasound of the lower limbs as a reference test, in a population of non-diabetic subjects over 70 years old with lower limb ulcers and without chronic renal failure. METHODS: We included 50 patients, 100 lower limbs from the vascular medicine department of the Paris Saint-Joseph hospital from December 2019 to May 2021. RESULTS: We found a sensitivity of 54.5% for the ankle brachial index and a specificity of 67.6%. Regarding the toe brachial index, the sensitivity was 80.3% and the specificity 44.1%. We could explain the low sensitivity of the ankle brachial index in our population by the mediacalcosis of elderly subjects, avoidable with the measurement of the toe blood pressure index, which had a better sensitivity. CONCLUSION: In a population of subjects over 70 years of age with a lower limb ulcer, without diabetes and without chronic renal failure, it would seem judicious to use the ankle brachial index in association with the toe brachial index for the diagnosis of peripheral arterial disease, followed by an arterial Doppler ultrasound of the lower limbs in order to evaluate the lesion profile of patients with a result of less than 0.7 of toe brachial index.

Peri-procedural complications following endovascular revascularization for critical limb ischemia.

OBJECTIVE: Revascularization procedures are considered the cornerstone of therapy in patients with critical limb ischemia (CLI) and multiple procedures are often required to attain limb salvage. The aim of the present study is to determine the prevalence of peri-procedural complications after endovascular procedure, and to determine the clinical and biological characteristics of patients associated to the risk of peri-procedural complications. METHODS: From November 2013 to May 2021, 324 consecutive patients were retrospectively included, of whom 99 underwent more than one revascularization procedure for contralateral CLI or clinical recurrence of CLI. A total of 532 revascularizations were performed. Clinical and biological parameters were recorded at baseline before endovascular revascularization. The occurrence of a peri-procedural complication (local complications, fatal and non-fatal major bleeding or cardiovascular events) was recorded up to 30days after revascularization. Univariate and multivariate analyses were performed to study the parameters associated with per-procedural complications. A P<0.05 was considered as statistically significant. RESULTS: A total of 324 consecutive patients were included, 177 men and 147 women with CLI, with a mean age of 77.6±11.9years. Most of these patients had cardiovascular comorbidities (41% with a history of coronary heart disease, 78% treated hypertensive patients, 49% diabetic patients). Peri-procedural mortality occurred in 13 patients (4%) and 9 patients (2.8%) experienced major amputation at one-month following revascularization. Among the 532 revascularization procedures, 99 major bleeding events (22.8% of the cohort population) and 31 cardiovascular events (8.6% of the cohort population), were recorded in the peri-procedural period. Cardiovascular events were associated with peri-procedural mortality. Complications at the puncture site occurred during 38 of the 532 procedures (10.2% of the cohort population). Compared with patients undergoing a single revascularization procedure, patients with multiple procedures presented a higher risk of major bleeding events (48.5% vs. 11.6%, P<0.0001) and access site complications (20.2% vs. 5.78%, P<0.0001). In multivariate analysis, pulse pressure <60mmHg and hemoglobin level <10g/dl were correlated with the occurrence of major bleeding events; left ventricular ejection fraction<60% and the absence of statin treatment were correlated with the occurrence of cardiovascular complications; a high chronological rank of revascularization was correlated with the occurrence of local complication. Finally, age and gender were not associated with the occurrence of peri-procedural complication. CONCLUSION: The present results highlight that multiple revascularization procedures for limb salvage are required in almost one third of the population with critical limb ischemia and were associated with the risk of major bleeding events and access site complications. The most frequent complications of peripheral vascular interventions were major bleeding events. Adverse cardiovascular events were related with peri-procedural mortality. Anemia, blood pressure, left ventricular ejection fraction and statin treatment are important parameters to consider for peri-procedural outcomes, independently of age, gender and the chronological rank of revascularization procedure.

Incident cardiovascular events and early mortality in patients with revascularized critical limb ischemia.

OBJECTIVES: Patients with critical limb ischemia (CLI) present a high risk of cardiovascular events and death. This study aimed to investigate the incidence of major adverse cardiovascular events (MACE) and one-year mortality in patients undergoing percutaneous revascularization procedure for CLI. METHODS: This investigation is a retrospective analysis of an ongoing cohort study in patients with CLI undergoing endovascular revascularization, hospitalized in the vascular medicine department from November 2013 to December 2018. Major cardiovascular events were collected during the first year after revascularization procedure and were defined as heart failure, acute coronary syndrome, ischemic stroke and sudden death. Mortality and major limb amputations, defined as above-the-ankle amputation, were determined during the one-year follow-up period. Multivariate logistic regression analyses were performed to identify factors independently associated with the occurrence of MACE and one-year mortality after revascularization procedure. A P≤0.05 was considered as statistically significant. RESULTS: The study included 285 consecutive patients, 157 men (55%) and 128 women (45%), with a mean age of 77.8±12 years. Treated hypertension was present in 222 (78%) patients; diabetes was present in 137 (48%) patients; 112 (39%) patients had known coronary heart disease and 20 (7%) patients were dialysis dependent. During the one-year follow-up after revascularization procedure, 75 (26.3%) patients presented an incident cardiovascular event, of whom 19 (6.7%) patients in the perioperative period. Cumulative mortality rate was 26.7% (76 patients) mostly from cardiovascular causes. Twenty-five patients (8.8%) experienced major amputation. In multivariate analysis, the occurrence of MACE was associated with an increased mortality risk (HR 6.96 (2.99-16.94), P<0.001). Other variables associated with an increased mortality were living in a nursing home and malnutrition. Decompensated heart failure and coronary heart disease were both associated with incident MACE in multivariate analysis, independently of confounders. CONCLUSION: In the present study population, incident MACE were prevalent in the year following endovascular revascularization procedure in patients with CLI and were associated with an increased risk of mortality. Coronary heart disease and decompensated heart failure are important contributors for the occurrence of MACE. In this elderly patient population with CLI, these results should be taken into account during the multidisciplinary team meeting before consideration of revascularization procedure.

Characteristics and outcomes of octogenarians with revascularized critical limb ischemia: Impact of altered cardiac function for early mortality.

OBJECTIVE: Patients with critical limb ischemia (CLI) present with advanced age and end-stage organ damage, in particular heart failure. The aim of the present study is to describe clinical and biological characteristics in octogenarian patients with CLI compared to their younger counterparts and to determine the peri-procedural risk and early mortality after endovascular procedure. METHODS: From November 2013 to May 2019, 315 consecutive patients were retrospectively included. Clinical and biological parameters were recorded at baseline before endovascular revascularization. The main outcome was total 1-year mortality. RESULTS: The study included 170 octogenarians and 145 non-octogenarians. The mean age of octogenarian patients was 86.9±4.8 years, almost 20 years higher than that registered in non-octagenarians patients (67.4±8.6 years). Octogenarian patients were mostly women (59.4%), presented with lower body mass index (23.8±4.4kg/m2), lower serum albumin level (31.5±5.4g/L) and lower creatinine clearance (66.1±24.5mL/mn) than younger counterparts. They were more likely to be institutionalized in a nursing home (27.1%). In the peri-procedural period, major bleeding occurred in 40 patients (12.7%), without statistical significance between the two age groups. Peri-procedural mortality occurred in 12 patients (3.8%), of whom 10 patients (83%) were octogenarians. Cumulative mortality rate was 25.4% (80 patients) during the one-year follow-up period: 58 octogenarians died (34.1%) compared to 22 non-octogenarian patients (15.2%), P<0.001. Cardiovascular events were highly prevalent, accounting for 40% of overall mortality. Twenty-five patients (8%) experienced major amputation, without significant difference between the two age groups. In octogenarian population, institutionalized status (P=0.004) and BNP level (P=0.001) were positively correlated with mortality whereas systolic blood pressure (P<0.001), left ventricular ejection fraction (P=0.003), serum albumin (P=0.020), C-Reactive protein (P=0.020) and renin-angiotensin system inhibitors at hospital discharge were negatively correlated with mortality. In multivariate analysis for mortality, only BNP level≥500pg/mL (HR 3.27; 95% CI 1.04-10.97; P=0.04), was correlated with mortality, independently of other confounders. CONCLUSION: In the present study population, octogenarians represent a rather distinct CLI population, 20 years of age older as compared to non-octogenarians, with prevalent malnutrition and institutionalized status. The present results underline a substantial one-year mortality rate of 34.1% in this elderly population following revascularization procedure with a 6% peri-procedural mortality. Decompensated heart failure is an important contributor for mortality.

Prevalence and management of antivitamin K overdose in a hospital setting.

INTRODUCTION: Vitamin K antagonist (VKA) related adverse events are the first cause for iatrogenic events in France, particularly due to the narrow therapeutic margin. The risk of bleeding increases significantly when the INR level is ≥5. The main objective of this study was to assess the prevalence of VKA overdose in a hospital setting (at D2 of hospital entry) and to evaluate physicians' adherence to clinical practice guidelines for the management of VKA overdose according to French National Authority for Health recommendations. METHODS: This single-center retrospective observational study consisted in querying the computerized database of a Parisian hospital on 21275INR determinations (3995 patients, 6813 hospital stays) performed between 2013 and 2018. RESULTS: An INR level ≥5 was noted during 350 (6%) of the hospital stays, in 331 patients (of whom 57% were women). The mean age of the patient population with an INR≥5 was 81.1 years. Infection, heart failure and renal failure were the most frequent acute medical conditions for hospital admission. Twenty-three patients (7%) had a bleeding complication, 11 of which were major bleeding complications. Older age was associated with the severity of bleeding complications. Fifteen in-hospital deaths (4%) were reported, not related to bleeding events. The management of VKA overdose did not comply with the recommendations in 43% of cases, in particular for the highest INRs (50% of noncompliance for an INR>6.4). Non-compliance with recommendations for VKA overdose was related to: the delay until the INR was checked (44% of cases); the indication for prescribing vitamin K (34% of cases); the dose or route of administration of vitamin K therapy (19% of cases); and the interruption or not of VKA therapy (12% of cases). CONCLUSION: The management of VKA overdose in a hospital setting remains non-compliant with the recommendations in almost half of the cases, mainly due to the delayed INR control and inappropriate management of vitamin K therapy. Computerized alert system would be helpful for personalized patient management and improved pharmacovigilance to prevent iatrogenic VKA events.

Foot ischemia related to essential thrombocytemia and atherosclerosis.

We report two cases of foot ischemia combining microvascular thrombosis related to essential thrombocytemia (ET) and a proximal ulcerating atherosclerotic plaque. This suggests that myeloproliferative neoplasms could also trigger distal embolism from an unstable atherosclerotic plaque by creating a prothrombotic status. These distal ischemic events were the first ET manifestation and therefore lead to myeloproliferative neoplasm diagnosis. In ET, thrombosis event can occur with a normal platelet count. Furthermore, hemogram should be regularly controlled among JAK2 muted patients considering the frequent evolution from isolated JAK2 mutation to ET.

Patients with atherosclerotic peripheral arterial disease have a high risk of lung cancer: Systematic review and meta-analysis of literature.

PURPOSE: Lung cancer and atherosclerosis share common risk factors. Literature data suggest that the prevalence of lung malignancy in patients with peripheral arterial disease (PAD) is higher than in the general population. Our goal was to determine, through a systematic literature review, the prevalence of lung cancer in patients with PAD. METHODS: We consulted available publications in the Cochrane library, MEDLINE, PUBMED, EMBASE, and ClinicalTrials.gov. We included all articles, written in English or French, published between 1990 and 2020 reporting the prevalence of lung cancer in patients with PAD (atherosclerotic aortic aneurysm or peripheral occlusive diseases). Patients with coronary artery disease, cardiac valvulopathy or carotid stenosis were not included. We did not include case reports. We performed a critical analysis of each article. Data were collected from two independent readers. A fixed effect model meta-analysis allowed to estimate a summary prevalence rate. RESULTS: We identified 303 articles, and selected 19 articles according to selection criteria. A total of 16849 patients were included (mean age 68.3 years, 75.1% of males). Aortic aneurysms were found in 29% of patients and atherosclerotic occlusive disease in 66% of patients. Lung cancer was identified in 538 patients, representing a prevalence of 3%. DISCUSSION: Lung cancer is found in 3% of patients with atherosclerotic PAD. This prevalence is higher than that found in lung cancer screening programs performed in the general population of smokers and former smokers. These patients should be screened for lung cancer. Their selection may dramatically increase the benefit of lung cancer screening.

Consistency of thrombophilia testing in a reference center according to the current guidelines.

OBJECTIVE: The clinical relevance of hereditary thrombophilia (HT) testing in venous thromboembolic disease (VTE) is limited to specific guidelines. The present study aimed to evaluate the consistency of HT prescriptions in clinical practice according to the current French guidelines. METHODS: This study was conducted from April 2017 to February 2018 in a specialized haemostasis centre and included 58 consecutive patients referred by their clinicians for thrombophilia screening (56 patients following a personal VTE event and 2 asymptomatic relatives of a first-degree patient who had had VTE). One experienced clinician met every patient and assessed a pre-test prediction for the presence or absence of HT based on the clinical characteristics of VTE which was compared to the HT biological results. RESULTS: Among the 58 patients referred to our specialized haemostasis centre, 60% were outside the scope of recommendations for thrombophilia screening. Eight patients were diagnosed with HT. Six out of 8 (75%) patients with diagnosed HT had a history of unprovoked VTE event. Familial history with VTE was a poor predictor for positive HT testing among relatives. The positive and negative predictive values of the clinical prediction were respectively of 19% and 89%. CONCLUSION: The present results underline that screening for HT remains too largely prescribed. Pre-test physician's feeling for the presence of HT was neither sensitive nor specific. Increasing physicians' awareness on this issue and current recommendations should limit prescriptions of HT tests while providing the best possible care for patients with VTE.

Ischemic stroke and non-valvular atrial fibrillation: When to introduce anticoagulant therapy?

About 20 to 30% of ischemic strokes are related to non-valvular atrial fibrillation. This type of situation is particularly at risk for both recurrence of the ischemic event and the hemorrhagic transformation of this stroke. The timing of the introduction or going back to the anticoagulant therapy in these patients remains a difficult issue, with a complex benefit-risk balance that needs to be assessed. Randomized controlled studies are lacking and current recommendations do not allow for clear decision making. The administration of a curative anticoagulant within 72 hours after the event is not recommended in the absence of demonstrated efficacy in preventing recurrence at this stage and because of the risk of intracerebral hemorrhage. This attitude can nevertheless be qualified by a transient accident or ischemic accident of very small size, and in the absence of any other risk factor for intra- or extra-cerebral hemorrhage. From the 4th day, after an appropriate case by case evaluation, the introduction of anticoagulant would be possible within a time which will remain at the appreciation of the medical teams. If the patient's risk of an intracerebral hemorrhage or general bleeding is transiently increased, it will be preferable to wait at least 2 weeks after the stroke. If this risk persists in the long term, the decision of the administration or not of an anticoagulant will have to be made with a multidisciplinary consultation. Vitamin K antagonists or direct oral anticoagulants may be prescribed as first-line therapy for the prevention of recurrence of ischemic stroke in a non-valvular atrial fibrillation patient. The choice will be based on the clinical and biological data of each patient. Direct oral anticoagulants have not shown superiority in the prevention of ischemic recurrence but open up new prospects for earlier treatment if their lesser risk of bleeding is confirmed after further studies.

Innovative endovascular approach for limb salvage in critical limb ischemia.

In the absence of feasible revascularization, nearly one third of patients with critical limb ischemia experienced major amputation at 6 months. In patients with an independent living status, this decision is difficult to support without exhausting all chances to attain limb salvage and preserve functional autonomy. The present report describes a new procedure of revascularization by performing a full endovascular extra-anatomic femoropopliteal bypass for the treatment of limb-threatening ischemia. The patient presented with extensive tissue loss and a short-term risk of major amputation. She had experienced previous failure of conventional surgical and endovascular revascularization procedures and ligation of proximal femoral artery precluded any further revascularization attempt. Limb salvage was achieved with this endovascular revascularization procedure with complete wound closure. The patient still presents an independent living status and preserved functional autonomy without wound recurrence after a follow-up of more than 5 years.

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.