Availability of medical and endovascular therapies for venous thromboembolism: a global survey for World Thrombosis Day.

BACKGROUND: Data on availability, affordability, and accessibility is key for the planning of global strategies to reduce the burden of venous thromboembolism (VTE). OBJECTIVES: A survey was conducted for the 10th anniversary of World Thrombosis Day to assess the availability of VTE therapies worldwide and challenges in uniform implementation. METHODS: We gathered information on the approval status, availability, utilization, occurrence of shortages, and spread of medical and interventional therapies for VTE. Furthermore, we collected information by accessing or contacting national or continental medicines agencies, manufacturers or distributors, and online drug repositories. RESULTS: We obtained data from a total of 69 countries: 33 countries in Europe, 19 in Asia, 7 in the Americas, 9 in Africa, and 1 in Oceania. Unfractionated heparin, low-molecular-weight heparin, and vitamin K antagonists were available in almost all countries, but shortages were recorded in 13%, 19%, and 15% of them, respectively. Direct oral anticoagulants were available in approximately three-quarters of the surveyed countries. At least one parenteral medication for heparin-induced thrombocytopenia was available in 57% of countries and a shortage was reported in 9% of these. Shortage of thrombolytics was recorded in 50% of countries. Overall, at least one type of catheter-directed therapy system was approved for use in 77% of countries and available in 23% of surveyed institutions. Our findings revealed notable geographic disparities in the worldwide availability of VTE therapies, the access to which appeared to be limited by economic and geopolitical factors. CONCLUSION: We anticipate that this comprehensive information will play a pivotal role in highlighting the shortcomings of VTE therapies and the lack of homogeneous availability globally.

Acoustic pulse thrombolysis complemented by ECMO improved survival in patients with high-risk pulmonary embolism.

BACKGROUND: The optimal treatment of high-risk pulmonary embolism (PE) with cardiac arrest is still controversial although various treatment approaches have been developed and improved. Here, we present a serie of patients with high-risk PE showing hemodynamic collapse, who were successfully treated with extracorporeal membrane oxygenation (ECMO) as an adjunct to EKOS™ acoustic pulse thrombolysis (APT). METHODS: From April 2016 to June 2020, 29 patients with high-risk PE with cardiac arrest were retrospectively included. The mean age was 55.3 ± 9.2 years. A total of 12 (41.3%) patients were female. All patients had cardiac arrest, either as an initial presentation or in-hospital after presentation. All patients exhibited acute symptoms, computed tomography evidence of large thrombus burden, and severe right ventricular dysfunction. Primary outcome was all-cause 30-day mortality. RESULTS: Twenty-two patients survived to hospital discharge, with a mean intensive care unit stay of 9.9 ± 1.6 days (range: 7-22 days) and mean length of hospital stay of 23.7 ± 8.5 days (range: 11-44 days). Six patients died from refractory shock. Ninety-day mortality was 24.1% (7/29). The Mean ECMO duration was 3.5 ± 1.1 days and the mean RV/LV ratio decreased from 1.31 ± 0.17 to 0.92 ± 0.11 in patients who survived to discharge. The mean tissue plasminogen activator dose for survivor patients was 20.5 ± 1.6 mg. CONCLUSION: Patients with high-risk pulmonary embolism who suffer a cardiac arrest have high morbidity and mortality. APT complemented by ECMO could be a successful treatment option for the patients who have high-risk PE with circulatory collapse.

An update on the global use of risk assessment models and thromboprophylaxis in hospitalized patients with medical illnesses from the World Thrombosis Day steering committee: Systematic review and meta-analysis.

INTRODUCTION: Venous thromboembolism (VTE) is a leading cause of cardiovascular morbidity and mortality. The majority of VTE events are hospital-associated. In 2008, the Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) multinational cross-sectional study reported that only approximately 40% of medical patients at risk of VTE received adequate thromboprophylaxis. METHODS: In our systematic review and meta-analysis, we aimed at providing updated figures concerning the use of thromboprophylaxis globally. We focused on: (a) the frequency of patients with an indication to thromboprophylaxis according with individual models; (b) the use of adequate thromboprophylaxis; and (c) reported contraindications to thromboprophylaxis. Observational nonrandomized studies or surveys focusing on medically ill patients were considered eligible. RESULTS: After screening, we included 27 studies from 20 countries for a total of 137 288 patients. Overall, 50.5% (95% confidence interval [CI]: 41.9-59.1, I2 99%) of patients had an indication to thromboprophylaxis: of these, 54.5% (95% CI: 46.2-62.6, I2 99%) received adequate thromboprophylaxis. The use of adequate thromboprophylaxis was 66.8% in Europe (95% CI: 50.7-81.1, I2 98%), 44.9% in Africa (95% CI: 31.8-58.4, I2 96%), 37.6% in Asia (95% CI: 25.7-50.3, I2 97%), 58.3% in South America (95% CI: 31.1-83.1, I2 99%), and 68.6% in North America (95% CI: 64.9-72.6, I2 96%). No major differences in adequate thromboprophylaxis use were found across risk assessment models. Bleeding, thrombocytopenia, and renal/hepatic failure were the most frequently reported contraindications to thromboprophylaxis. CONCLUSIONS: The use of anticoagulants for VTE prevention has been proven effective and safe, but thromboprophylaxis prescriptions are still unsatisfactory among hospitalized medically ill patients around the globe with marked geographical differences.

Global reporting of pulmonary embolism-related deaths in the World Health Organization mortality database: Vital registration data from 123 countries.

INTRODUCTION: Pulmonary embolism (PE) has not been accounted for as a cause of death contributing to cause-specific mortality in global reports. METHODS: We analyzed global PE-related mortality by focusing on the latest year available for each member state in the World Health Organization (WHO) mortality database, which provides age-sex-specific aggregated mortality data transmitted by national authorities for each underlying cause of death. PE-related deaths were defined by International Classification of Diseases, Tenth Revision codes for acute PE or nonfatal manifestations of venous thromboembolism (VTE). The 2001 WHO standard population served for standardization. RESULTS: We obtained data from 123 countries covering a total population of 2 602 561 422. Overall, 50 (40.6%) were European, 39 (31.7%) American, 13 (10.6%) Eastern Mediterranean, 13 (10.6%) Western Pacific, 3 (2.4%) Southeast Asian, and 2 (1.6%) African. Of 116 countries classifiable according to population income, 57 (49.1%) were high income, 42 (36.2%) upper-middle income, 14 (12.1%) lower-middle income, and 3 (2.6%) low income. A total of 18 726 382 deaths were recorded, of which 86 930 (0.46%) were attributed to PE. PE-related mortality rate increased with age in most countries. The reporting of PE-related deaths was heterogeneous, with an age-standardized mortality rate ranging from 0 to 24 deaths per 100 000 population-years. Income status only partially explained this heterogeneity. CONCLUSIONS: Reporting of PE-related mortality in official national vital registration was characterized by extreme heterogeneity across countries. These findings mandate enhanced efforts toward systematic and uniform coverage of PE-related mortality and provides a case for full recognition of PE and VTE as a primary cause of death.

Successful treatment of right heart thrombus and high-risk pulmonary embolism with acoustic pulse thrombolysis using EKOS endovascular system.

Currently, the only widely accepted indication for interventional treatment in cases of pulmonary embolism is hemodynamic instability or cardiogenic shock. However, the presence of a right-heart thrombus along with a pulmonary embolism is a poor prognostic indicator, and catheter directed thrombolysis with use of thrombolytic agents should also be considered in this circumstance. Optimal management of right heart thrombus and high-risk pulmonary embolism is still uncertain. Herein, we present the case of an 81-year-old woman who presented at our hospital after progressive dyspnea and a syncopal event. The transthoracic echocardiography showed massive bilateral pulmonary, right ventricular and mobile atrial thrombus and also right-sided enlargement. The patient was successfully treated with acoustic pulse thrombolysis using the EKOS EkoSonic system and echocardiography revealed complete resolution of her right-heart thrombus and her high-risk pulmonary embolism 2 days later.

Treatment of complex atherosclerotic femoropopliteal artery disease with a self-expanding interwoven nitinol stent: Midterm results.

OBJECTIVE: To examine the efficacy and durability of an interwoven self-expanding nitinol stent for the treatment of superficial femoral and popliteal arteries. METHOD: Consecutive patients with severely diseased superficial femoral and popliteal arteries who received SUPERA® stents were retrospectively identified.The patients were followed for 12 months by Doppler ultrasound examinations, stent roentgenograms, and estimation of Rutherford-Becker class and ankle-brachial index. RESULTS: From July 2012 to May 2014, 42 limbs in 36 patients (mean age, 61.5 ± 7.5 years; 75% male) were treated with angioplasty and primary stenting. Total occlusions were present in 14 limbs, and 63.8% had either moderate or severe calcification. The mean (±SD) lesion length was 105 mm (±28). Primary patency was 91.4% at 6 months and 85.7% at 12 months. The ankle brachial index increased from 0.57 ± 0.19 preoperative to 0.91 ± 0.12 postoperative. There was no procedural or device-related morbidity or mortality after revascularization and only one major amputation was observed on follow-up. CONCLUSIONS: Our experience shows that, Supera stents are safe and effective in our cohort of patients, with acceptable patency rates. There were no stent fractures so far even with stenting of the femoropopliteal segments. Stent design provides a viable option for high-grade obstructive disease in the femoropopliteal artery.

WITHDRAWN: Subsegmental Thrombus in COVID-19 Pneumonia: Immuno-Thrombosis or Pulmonary Embolism? Data Analysis of Hospitalized Patients with Coronavirus Disease.

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Endophlebectomy of the common femoral vein and endovascular iliac vein recanalization for chronic iliofemoral venous occlusion.

BACKGROUND: Chronic post-thrombotic occlusion of the iliofemoral veins causes significant morbidity, which can be alleviated if venous drainage is restored. We report our technique of surgical endophlebectomy and patchplasty of the common femoral vein (CFV) in conjunction with iliac vein stenting to restore venous flow from the infrainguinal venous system to the vena cava. METHODS: There were 157 patients who underwent CFV endophlebectomy combined with iliocaval recanalization. Questionnaires were completed both preoperatively and postoperatively to allow comparison. These included the Clinical, Etiology, Anatomy, and Pathophysiology clinical classification; the Venous Clinical Severity Score; the Villalta scale; the Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms; and the 36-Item Short Form Health Survey quality of life questionnaire. RESULTS: Mean follow-up duration was 14.4 ± 2.9 months (range, 10-29 months). The mean preoperative Venous Clinical Severity Score was 15.3 ± 2.2, and this fell to 6.1 ± 1.8 after treatment (P < .001). The mean preoperative Villalta score dropped from 12.7 ± 2.6 to 6.3 ± 1.4 (P < .001). The quality of life and symptom severity scores were improved after 3 months by 17.2 points for quality of life (P < .001) and 20.5 points for symptom severity (P < .001). Primary patency was 81% (124/153) and secondary patency was 89.5% (137/153) at 12 months. Wound complications related to groin incision and lymphatic fistulas were observed in 22.8% (35/153) and 28.7% (44/153), respectively. CONCLUSIONS: The hybrid operation of CFV endophlebectomy in conjunction with iliac vein recanalization should be considered a safe and effective treatment option in patients with severe post-thrombotic syndrome and iliofemoral veno-occlusive disease.

The feasibility of robotic-assisted concomitant procedures during mitral valve operations.

BACKGROUND: In this study, we present our clinical experience and midterm results with the robotic-assisted concomitant procedures during mitral valve operations. METHODS: Between March 2010 and February 2018, a total of 34 patients (8 males, 26 females; mean age 58.3 years; range, 34 to 78 years) who underwent robotic-assisted concomitant procedures during mitral valve surgery were retrospectively analyzed. Demographic characteristics of the patients, comorbidities, medical, and surgical histories, operative and laboratory results, electrocardiographic findings, postoperative intensive care unit and ward outcomes, and cardiac follow-up data were recorded. Atrial fibrillation-related medication use, stroke, or other thromboembolic events, and electrocardiographic reports in patients who underwent cryoablation were reviewed at three and 12 months after the operation. RESULTS: A total of 76 robotic-assisted concomitant procedures were performed during mitral valve repair (n=11) or replacement (n=23) in 34 patients. These procedures were cryoablation (n=29), tricuspid valve repair (n=6), tricuspid valve replacement (n=2), left atrial appendage ligation (n=32), atrial septal defect and patent foramen ovale closure (n=5), and left atrial thrombectomy (n=2). The mean preoperative EuroSCORE values were 5.1±2.5. The mean duration of cardiopulmonary bypass and cross-clamp was 156±69.4 min and 101±42 min, respectively. Normal sinus rhythm was restored in 85% of the patients (24/28) after cryoablation and two patients (5.8%) had permanent pacemaker within a year during follow-up. There was one (2.9%) mortality in the early postoperative period due to hemorrhage related to the posterior left ventricular wall rupture. No blood product was used in 82.4% of the patients. One patient had a transient cerebral event and symptoms regressed completely within two months. CONCLUSION: Technological improvements and growing experience can decrease the suspects related to prolonged operational duration during robotic-assisted cardiac surgery. Concomitant procedures in addition to mitral valve operations can be performed with low complication rates in centers with experience of robotic surgery.

The effect of Angiojet rheolytic thrombectomy in the endovascular treatment of lower extremity deep venous thrombosis.

Objective To evaluate the clinical safety and effectiveness of percutaneous rheolytic thrombectomy in patients with acute lower extremity deep venous thrombosis. Method Sixty-eight consecutive patients with acute massive lower extremity deep venous thrombosis were included in this retrospective study. A percutaneous rheolytic thrombectomy device (Angiojet ® Rheolytic thrombectomy catheter, Boston Scientific, Marlborough, MA, USA) was used in all patients in an angiography suite through ipsilateral popliteal vein access. Thrombus clearance and complications were evaluated. Furthermore, patients underwent a clinical evaluation according to a modified Villalta scale for the investigation of post thrombotic syndrome in follow-up. The Venous Clinical Severity Score, Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Sym questionnaires were completed preoperatively and readministered postoperatively. Results Overall thrombus clearance (complete recanalization was achieved in 58 patients (85.2%) and partial recanalization was achieved in 7 patients (10.2%) confirmed through venographic assessment was achieved in 95.5% of the patient population. The mean Venous Clinical Severity Score preoperatively was 13.1 ± 2.2 and decreased to 4.0 ± 1.3 postoperatively (P < 0.01). The Villalta scale dropped from 12.9 ± 2.8 to 5.5 ± 1.4 postoperatively (P < 0.001). Overall quality of life and symptoms improved as assessed by Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Sym (P < 0.01 and 0.02, respectively). Only three minor bleedings were seen but none of the patients suffered from major bleeding, symptomatic pulmonary embolism, death, or other procedure related complications. Fifty-nine out of 65 patients (90.7%) who were treated successfully with rheolytic thrombectomy remained patent at 12 months according to DUS and five patients (7.3%) developed a mild post thrombotic syndrome. Conclusion Rheolytic thrombectomy with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical symptoms. This technique is a safe, effective and easily performed method of endovascular treatment with a low rate of major treatment complications and shows promising clinical mid-term results.

Retrograde Popliteal Access to Percutaneous Peripheral Intervention for Chronic Total Occlusion of Superficial Femoral Arteries.

OBJECTIVE: The aim of this study is to present our initial experience with the use of the retrograde popliteal artery access in patients with chronic total occlusions of superficial femoral artery (SFA). METHOD: From July 2012 to May 2014, a total of 28 patients (20 men, mean age 61.2 ± 11.5 years) with total occlusion of the SFA and good distal runoff were treated with percutaneous atherectomy, balloon angioplasty, and stenting (mean length 165.3 ± 57.5 mm, range 72-336 mm). All patients had severe claudication or critical limb ischemia, and most of the lesions were TransAtlantic Inter-Society Consensus classification type D (n = 21). RESULTS: Technical success was achieved in all cases. In majority (26, 92.8%) of the patients, endoluminal recanalization was possible from the popliteal access; SFA recanalization in the other 2 cases was obtained through the subintimal space. During a mean follow-up of 12.9 ± 2.5 months, claudication, severity, rest pain, and toe ulcers improved significantly. Ankle-brachial index changed from 0.54 ± 0.11 to 0.91 ± 0.2 at 1 year after intervention ( P < .001), and patency rates at 1, 6, and 12 months after interventions were 100%, 92.8%, and 85.7%, respectively. One pseudoaneurysm and 1 arteriovenous fistula were found in the popliteal region on duplex examinations. There were 2 in-stent restenosis and 3 occlusions during the 12-month follow-up. These occlusions were treated with reendovascular procedures. Our secondary patency rate was 96.4%. No stent fracture was observed. CONCLUSION: The retrograde popliteal artery approach under duplex guidance can be considered as safe, efficient, and the primary SFA recanalization strategy in carefully selected patients, with competitive immediate and mid-term results.

What are the Prevalence of Abdominal Aortic Aneurysm in Patients with Chronic Obstructive Pulmonary Diseases and the Characteristics of These Patients?

OBJECTIVE: To determine the prevalence of abdominal aortic aneurysm (AAA) in patients with chronic obstructive pulmonary disease (COPD) and to assess the characteristics of these patients. MATERIALS AND METHODS: Stable COPD patients (age, >40 years) were included in the study between January 2014 and June 2014. Patients with acute exacerbations and a previous lung resection were excluded. Data regarding demographic characteristics were recorded. The modified Medical Research Council (mMRC) dyspnea scale was used to assess the severity of breathlessness. The COPD Assessment Test (CAT) was performed. Abdominal aortic diameter was measured using abdominal ultrasonography (AUS), and AAA was diagnosed as an aortic diameter of ≥30 mm at the renal artery level. RESULTS: In total, 82 patients were examined. AAA was detected in five (6.1%) patients. Diabetes mellitus, hypertension, and coronary artery disease were present in four patients with AAA. The average mMRC score was 3.2±0.4, and the mean CAT score was 18.4±6.0. Aneurysmal diameter was >50 mm in four patients and 37 mm in one patient. Statistically significant differences were found between patient with AAA and those without AAA with respect to the mean abdominal aortic diameters at the renal artery and iliac artery levels (p=0.012 and 0.002, respectively). CONCLUSION: Our findings suggest that AAA is associated with COPD, with a prevalence rate of 6.1%. AAA is usually asymptomatic until a clinical status of rupture, which is associated with a higher mortality risk. Early diagnosis of AAA is lifesaving. In COPD patients, AAA might be easily determined using AUS, which is a noninvasive and relatively cheap procedure.

Combined treatment with endovenous laser ablation and compression therapy of incompetent perforating veins for treatment of recalcitrant venous ulcers.

Objective Patients with healed venous ulcers often experience recurrence of ulceration, despite the use of long-term compression therapy. This study examines the effect of closing incompetent perforating veins (IPVs) on ulcer recurrence rates in patients with progressive lipodermatosclerosis and impending ulceration. Methods Patients with nonhealing venous ulcers of >2 months' duration underwent duplex ultrasound to assess their lower extremity venous system for incompetence of superficial, perforating, and deep veins. Endovenous laser ablation (EVLA) of perforating veins was performed on patients with CEAP 6 disease with increasing hyperpigmentation, lipodermatosclerosis, and/or progressive malleolar pain. A minimum of 2 months of compressive therapy was attempted before endovenous ablation of IPVs. Demographic data, risk factors, CEAP classification, procedural details, and postoperative status were all recorded. Results Forty ulcers with 46 associated IPVs were treated with EVLA in 36 patients with CEAP 6 recalcitrant venous ulcers. Treated incompetent perforator veins were located in the medial ankle (85.7%), calf (10.7%), and lateral ankle (3.5%). Endovenous laser ablation was successful in 76% (35/46) with the first laser treatment of incompetent perforator veins and 15.2% (7/46) additional ablation procedures were performed. Of the 46 treated IPVs, 42 (91.3%) were occluded on the duplex examination at 12 months. The average energy administrated per perforating vein treated was 162 joule. Two patients reported localized paresthesia, which subsided spontaneously, but no deep venous thrombosis or skin burn was observed. Conclusion Especially in the case of liposclerotic or ulcerated skin in the affected region, PAP of IPVs is highly effective, safe, and appears to be feasible. Patients with active venous ulcers appear to benefit from EVLA of incompetent perforators in order to reduce the risk of ulcer recurrence.

Efficacy of intralesional recombinant human epidermal growth factor in chronic diabetic foot ulcers.

OBJECTIVE: The aim of this study was to explore the clinical effects of intralesional administration of an epidermal growth factor (EGF) up to complete wound closure. METHODS: Seventeen diabetic patients with full-thickness lower extremity ulcers of more than 4 weeks of evolution were enrolled in the study. Mean ulcer size was 15.5 +/- 7.5 cm(2). Intralesional injections of 75 µg of Heberprot-P three times per week for 5-8 weeks were given up to complete wound healing. RESULTS: Full granulation response was achieved in all patients in 32.4 +/- 6.6 days. Complete wound closure was obtained in 16 (94.1%) cases in 53.1 +/- 4.7 days. The most frequent adverse events were burning sensation, tremors, chills and pain at the site of administration. After 1-year follow-up, only one patient relapsed. CONCLUSIONS: Intralesional EGF administration up to complete closure can be safe, effective and suitable to improve healing of chronic diabetic foot ulcer (DFU).

Efficacy of rotational thrombectomy on the mortality of patients with massive and submassive pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) associated with hemodynamic instability has exceedingly high mortality. We describe our experience using percutaneous mechanical thrombectomy (PMT) in patients with massive PE (MPE) and submassive PE (SPE). METHODS: Thirty-six patients (16 males and 20 females; mean age, 51.4 ± 6.6 years) with massive and submassive PE were treated with PMT. All patients exhibited acute symptoms and computed tomography evidence of large thrombus burden and evidence of right ventricular (RV) dysfunction and/or failure. An Aspirex® percutaneous aspiration device was used in all patients. Clinical outcomes, hemodynamic recovery, RV and pulmonary artery pressures (PAP), blood gas changes, thrombus clearance, and complications were evaluated. RESULTS: Treatment of 36 patients resulted in complete thrombus clearance (≥ 90%) in 83.3% of the patients (n = 30) and near-complete (50% to 90%) clearance in 13.8%. Measurements before and after treatment showed a decrease in mean PAP (53 ± 5.8 mmHg versus 25.6 ± 6.3 mmHg in MPE group [p < 0.01] and 46 ± 7.7 versus 22 ± 3.6 in SPE group [p < 0.01]). One patient died from refractory shock. No cardiovascular deaths or recurrent PE were documented during clinical follow-up but one patient demonstrated evidence of mild cor pulmonale. CONCLUSIONS: This study demonstrates safety and effectiveness of percutaneous mechanical aspiration thrombectomy in patients with massive and submassive PE with a large thrombus burden.

Percutaneous aspiration thrombectomy in treatment of massive pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) associated with haemodynamic instability has exceedingly high mortality. We describe our experience using percutaneous mechanical thrombectomy (PMT) in patients with massive PE and right ventricle dysfunction. METHODS: Sixteen patients (11 males and five females; mean age, 55.7 ± 8.3 years) with massive PE were treated with PMT. A percutaneous Aspiration Device (8 French Aspirex® aspiration thrombectomy catheter, Straub Medical, Switzerland) was used in all patients. Clinical outcomes, right ventricle and pulmonary artery pressures (PAP), thrombus clearance and complications were evaluated. RESULTS: Treatment of 16 patients resulted in complete thrombus clearance (≥ 90%), in 87.5% of the patients and near-complete (50%-90%) clearance in 6.3%. Measurements before and after treatment showed a decrease in PAP (73 ± 11 mm Hg to 34 ± 8 mm Hg, P<.001). The RV/LV ratio decreased from 1.32 ± 0.15 to 0.84 ± 0.13 at follow-up (P<.001). One patient died from refractory shock. No cardiovascular deaths or recurrent PE were documented during clinical follow-up but one patient demonstrated evidence of mild cor pulmonale. CONCLUSIONS: This study demonstrates safety and effectiveness of percutaneous mechanical aspiration thrombectomy in patients with massive PE with a large thrombus burden.