Is Restenosis/Reocclusion after Femoropopliteal Percutaneous Transluminal Angioplasty (PTA) the Consequence of Reduced Blood Flow, Inflammation, and/or Hemostasis Disturbances?

Percutaneous transluminal angioplasty (PTA) is an established method for treatment of peripheral artery disease (PAD) of the femoropopliteal artery. However, in up to 50% of patients restenosis and/or reocclusion remain a frequent complication occurring in the first year after the procedure. In this study, we focused on the influence of compromised postprocedural infrapopliteal runoff of the affected limb, on the hypercoagulability as detected by a global hemostasis assay and on genetic predisposition to hypercoagulability and on the regulation of the inflammation through the nuclear receptor related 1 protein (NuRR1). Consecutive PAD patients treated by femoropopliteal PTA because of disabling claudication or critical limb ischemia were followed up by vascular ultrasound imaging at 1, 6, and 12 months after the procedure. Venous blood samples for hemostasis, inflammation, and gene analysis were obtained before and 24 h after PTA. One month after femoropopliteal PTA, 23% of patients with compromised runoff developed the combined end point restenosis/reocclusion in comparison to 11% with good runoff (p = 0.03). After 6 months, the differences were no longer significant. It was concluded that compromised postprocedural infrapopliteal runoff predisposes to early restenosis/reocclusion after femoropopliteal PTA and that the deterioration of infrapopliteal runoff in the year after femoropopliteal PTA is accompanied by worsening of long-term femoropopliteal patency. Patients were genotyped for the prothrombotic gene polymorphisms: platelet receptor glycoprotein IIIa T1565C, coagulation factor V G1691A, coagulation factor II G20210A, coagulation factor XII C(-4)T, and plasminogen activator inhibitor-1 4G5G. We were not able to show any association between these polymorphisms and the restenosis/reocclusion rate in patients treated with femoropopliteal PTA. Furthermore, no association between thrombin generation and restenosis/reocclusion rate was established. NuRR1 haplotypes significantly increased the restenosis/reocclusion rate after PTA (adjusted relative risks were 1.6, 95% CI 1.1–2.3 for haplotype 2 and 2.0, 95% CI 1.3–2.8 for haplotype 3). To conclude, this study suggested a significantly higher restenosis/reocclusion rate in patients with compromised runoff compared to patients with a good runoff 1 month after the procedure. Hypercoagulability was not associated with the restenosis/reocclusion rate, and the prothrombotic polymorphisms were equally distributed among patient with and without restenosis/reocclusion, suggesting minor or no role in restenosis/reocclusion. Haplotypes 2 and 3 in the NuRR1 gene significantly increased the restenosis/reocclusion rate, suggesting significant role of inflammation. In this ongoing study, further analysis on a larger group of patients is warranted

Effectiveness and safety of anticoagulant versus antiplatelet therapy in patients after endovascular revascularisation of the lower limb

Background: After revascularisation, patients with peripheral arterial disease (PAD) are routinely prescribed antiplatelet treatment (APT). Patients who receive anticoagulant treatment (ACT) due to comorbidity are an exception. We set out to determine possible differences in the effectiveness and safety between ACT and APT in patients after endovascular revascularisation of the lower limb arteries. Methods: In a single-centre retrospective cohort study, we analysed the data of 1,587 PAD patients who underwent successful endovascular revascularisation of the lower limb arteries due to disabling intermittent claudication or chronic critical limb ischemia over a 5-year period. Patients were divided into the ACT and APT groups based on their prescribed treatment. After balancing both groups’ baseline characteristics with propensity score matching, we compared the effectiveness and safety of both treatment regimens in the first year after revascularisation. Results: Compared to patients with APT, patients with ACT were older, and more often reported arterial hypertension, diabetes, chronic kidney disease, congestive heart failure, ischaemic heart disease, and prior stroke or transient ischaemic attack. After matching, the odds ratio (OR) for an effective outcome with ACT versus APT was 0.78 (95% CI 0.39–1.59; p=0.502), while the OR for a safe outcome with ACT versus APT was 4.12 (95% CI 0.82–20.73; p=0.085). Conclusions: Patients who required ACT were elderly, had more cardiovascular risk factors and had more advanced PAD than patients with APT. After matching, we found no statistically significant difference in the effectiveness and safety of both treatment regimens; however the wide OR confidence intervals warrant further research

ESVM Guideline on peripheral arterial disease

International audienc

Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations–State-of-the-Art.

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist

Prognostic factors for restenosis of femoral artery after the percutaneous transluminal angioplasty

Izhodišče: Perkutana transluminalna angioplastika (PTA) predstavlja prednosten način revaskularizacijskega zdravljenja periferne arterijske bolezni (PAB). Kljub napredku tehnologije pa je v področju stegenske arterije pojavnost ponovnih zožitev še vedno visoka. Namen: Proučiti smo želeli, kako na verjetnost ponovne zožitve stegenske arterije po PTA vplivajo arterijski iztok v golen, hemostatski potencial in nekateri genetski dejavniki. Preiskovanci in metode dela: V raziskavo smo vključili 206 zaporednih preiskovancev s PAB v fazi omejujoče intermitentne klavdikacije, pri katerih smo opravili PTA stegenske arterije. Preiskovance smo spremljali eno leto in z ultrazvočno preiskavo arterij mesec dni, pol leta in leto dni po posegu ocenili prehodnost zdravljene arterije. Uro pred posegom in 24 ur po posegu smo preiskovancem odvzeli kri za določitev laboratorijskih kazalnikov hemostaze in vnetja ter za analizo polimorfizmov v genih NR4A2 in PECAM1. Rezultati: Ponovna zožitev stegenske arterije je prizadela 45 % preiskovancev. Slab iztok v golen je povečal tveganje za ponovno zožitev po prvem mesecu (p = 0,005) in po šestih mesecih (p = 0,003), v naslednjih 6 mesecih pa ne (p = 0,628). Preiskovanci z zdravljeno arterijsko hipertenzijo so ponovno zožitev utrpeli redkeje kot tisti brez hipertenzije (OR 0,2195% CI: 0,07-0,67p = 0,009). V laboratorijskih izvidih smo pri preiskovancih s ponovno zožitvijo ugotovili podaljšano fazo zamika tvorjenja trombina (pred posegom p = 0,042, po posegu p = 0,027) in večji prispevek mikrodelcev na koncentracijo trombina (pred posegom p < 0,001, po posegu p = 0,006). Polimorfizmi posameznega nukleotida genov NR4A2 in PECAM1 na verjetnost ponovne zožitve niso imeli vpliva. Pri polimorfizmu rs1466408 gena NR4A2 smo po posegu ugotovili zmanjšano izražanje gena. V multivariatni analizi sta se kot napovedna dejavnika ponovne zožitve izkazala slab iztok v golen (OR 5,7295% CI: 1,73-18,95p = 0,004) in večja kompleksnost lezije, ocenjena s TASC II klasifikacijo (razred B vs razred A (OR 3,4395% CI: 1,51-7,79p = 0,003) in razred C vs razred A (OR 9,8395% CI: 3,34-28,95p < 0,001)). Zaključki: Slab iztok v golen in večja kompleksnost lezije glede na TASC II klasifikacijo pomembno vplivata na pojavnost ponovne zožitve stegenske arterije po PTA, medtem ko je zdravljena arterijska hipertenzija varovalni dejavnik. Povezave med povečano tvorbo trombina ter CHP in ponovno zožitvijo arterije nismo potrdili. Polimorfizmi posameznega nukleotida v nekodirajočih delih genov NR4A2 in PECAM1 niso vplivali na ponovno zožitev arterije.Background: Percutaneous transluminal angioplasty (PTA) is the preferred method of revascularization treatment of peripheral arterial disease (PAD). Despite advances in technology, the incidence of restenosis in the femoral artery is still high. Aim: We wanted to study how is the likelihood of the femoral artery restenosis affected by the infrapopliteal arterial run-off, haemostatic potential, and certain genetic factors. Patients and methods: The study included 206 consecutive patients with PAD and limiting intermittent claudication in whom PTA of the femoral artery was performed. Patients were monitored for one year and the patency of the treated artery was assessed by ultrasound examination of the arteries one month, six months and one year after the procedure. One hour before the procedure and 24 hours after the procedure, thrombin generation, overall haemostatic potential (OHP) and single nucleotide polymorphisms (SNPs) in the NR4A2 and PECAM1 genes were assessed. Results: Restenosis of the femoral artery occurred in 45% of patients. Poor infrapopliteal run-off increased the risk of restenosis after one month (p = 0.005) and after six months (p = 0.003), but not during the following 6 months (p = 0.628). Patients with treated arterial hypertension were less likely to experience restenosis than patients without hypertension (OR 0.2195% CI: 0.07-0.67p = 0.009). Patients with restenosis were found to have delayed phase time in thrombin generation (before procedure p = 0.042, after procedure p = 0.027) and a higher contribution of microparticles to thrombin concentration (before procedure p < 0.001, after procedure p = 0.006). SNPs of the NR4A2 and PECAM1 genes had no effect on the likelihood of restenosis. For the rs1466408 polymorphism of the NR4A2 gene, we found reduced gene expression after PTA. In the multivariate analysis, poor infrapopliteal run-off (OR 5.7295% CI: 1.73-18.95p = 0.004) and higher lesion complexity assessed by the TASC II classification (type B vs type A lesions (OR 3.4395% CI: 1.51-7.79p = 0.003) and type C vs type A lesions (OR 9.8395% CI: 3.34-28.95p < 0.001)) proved to predict restenosis. Conclusions: Poor infrapopliteal run-off and greater lesion complexity significantly influence the incidence of restenosis of the femoral artery after PTA, while treated arterial hypertension is a protective factor. The association of restenosis with thrombin generation and OHP was not confirmed. SNPs of the NR4A2 and PECAM1 genes did not affect the probability of arterial restenosis

Clinical Outcomes after Endovascular Revascularisation of the Femoropopliteal Arterial Segment in Patients with Anticoagulant versus Antiplatelet Therapy: A Single-Centre Retrospective Cohort Study

To prevent atherothrombotic events, patients with peripheral arterial disease are typically prescribed antiplatelet therapy (APT). However, some of them receive anticoagulant therapy (ACT) due to comorbidities. Our aim was to determine possible differences in the effectiveness and safety of both treatments in patients after endovascular femoropopliteal revascularisation. We retrospectively analysed 1247 patients after successful femoropopliteal revascularisation performed in a single tertiary medical centre and classified them into the ACT or APT group, based on their prescribed treatment. The groups were characterised by descriptive statistics, and their characteristics were adjusted for confounders by propensity score matching. Effectiveness and safety outcomes were assessed within one year after revascularisation. The odds ratio for the composite outcome of all-cause death, PAD exacerbation, and major amputation due to vascular causes with ACT versus APT was 1.21 (95% CI 0.53&ndash;2.21; p = 0.484). The odds ratio for major bleeding as defined by the International Society on Thrombosis and Haemostasis with ACT versus APT was 0.77 (95% CI 0.13&ndash;3.84; p = 0.251). We found no statistically significant difference in the effectiveness and safety of ACT, when compared to APT in patients with similar cardiovascular risk factors and other baseline characteristics. Further prospective research is warranted

Revascularization of Peripheral Arteries in Patients with Intermittent Claudication Decreases Inflammatory Biomarkers

Patients with intermittent claudication have significantly higher levels of inflammatory biomarkers, particularly interleukins, which is also a consequence of exercise limitation. Physical activity, which is one of the preventive measures against atherosclerosis, is associated with a decrease in inflammatory biomarkers. Therefore, in our study, we investigated the effects of revascularization of peripheral arteries in patients with intermittent claudication on functional capacity and levels of inflammatory markers. The study included 26 patients with intermittent claudication who underwent percutaneous transluminal angioplasty (PTA). Before the procedure and 2–4 months after successful revascularization, the ankle-brachial index (ABI), functional capacity using the treadmill test, and the walking impairment questionnaire (WIQ) were determined. Inflammatory biomarkers were also measured before and after procedures. Successful revascularization was associated with an increase in intermittent claudication: 120 (20–315) versus 300 (100–1000 m), P  < 0.001. Treadmill testing showed a significant increase in initial and maximal walking distance. After revascularization, ABI increased significantly (0.55 vs 0.82, P  < 0.003). Improvement in functional performance was also demonstrated by WIQ. Two to three months after revascularization, some inflammatory biomarkers decreased significantly: fibrinogen, interleukin-6 (IL-6), and interleukin-8 (IL-8). The high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-alpha (TNFα) also did not decrease significantly. The levels of some inflammatory markers: IL-6, TNFα, and fibrinogen were significantly related to the improvement in patients’ functional capacity. The results of our study show that successful revascularization of the lower limb arteries not only improves the functional capacity of patients with intermittent claudication, but also reduces the systemic inflammatory response and may have a preventive effect on local and concomitant other atherosclerotic diseases