Renal impairment (RI) has increased substantially over the last decades. In the absence of data from confirmatory research, real-life data on anticoagulation treatment and clinical outcomes of venous thromboembolism (VTE) in patients with RI are needed. In the SWIss Venous ThromboEmbolism Registry (SWIVTER), 2,062 consecutive patients with objectively confirmed VTE were enrolled. In the present analysis, we compared characteristics, initial and maintenance anticoagulation, and adjusted 90-day clinical outcomes of those with (defined as estimated creatinine clearance < 30 mL/min) and without severe RI. Overall, 240 (12%) patients had severe RI; they were older, and more frequently had chronic and acute comorbidities. VTE severity was similar between patients with and without severe RI. Initial anticoagulation in patients with severe RI was more often performed with unfractionated heparin (44 vs. 24%), and less often with low-molecular-weight heparin (LMWH) (52 vs. 61%) and direct oral anticoagulants (DOACs; 4 vs. 12%). Maintenance anticoagulation in patients with severe RI was more frequently managed with vitamin K antagonists (70 vs. 60%) and less frequently with DOAC (12 vs. 21%). Severe RI was associated with increased risk of 90-day mortality (9.2 vs. 4.2%, hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.41-3.65), but with similar risk of recurrent VTE (3.3 vs. 2.8%, HR: 1.19, 95% CI: 0.57-2.52) and major bleeding (2.1 vs. 2.0%, HR: 1.05, 95% CI: 0.41-2.68). In patients with severe RI, the use of LMWH versus any other treatment was associated with reduced mortality (HR: 0.37; 95% CI: 0.14-0.94; p = 0.036) and similar rate of major bleeding (HR: 0.59, 95% CI: 0.17-2.00; p = 0.39). Acute or chronic comorbidities rather than VTE severity or recurrence may explain increased early mortality in patients with severe RI. The higher rate of VTE recurrence, specifically fatal events, than major bleeding reinforces the need for effective anticoagulation in VTE patients with severe RI.

Free Access19. Unionstagung der Schweizerischen Gesellschaften für Gefässkrankheiten gemeinsam mit der Schweizerischen Gesellschaft für Ultraschall in der Medizin Sektion Gefässe / 19e Congrès de l’Union des Sociétés Suisses des Maladies Vasculaires en collaboration avec la Société Suisse d‘Ultrasons en Médecine Section VaisseauxPublished Online:November 06, 2018https://doi.org/10.1024/0301-1526/a000722PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInReddit SectionsMoreFiguresReferencesRelatedDetails Volume 47Issue Supplement 100November 2018ISSN: 0301-1526eISSN: 1664-2872 InformationVasa (2018), 47, pp. 1-46 https://doi.org/10.1024/0301-1526/a000722.© 2018Hogrefe AGPDF download

Part one addressed the value of duplex ultrasound in the diagnostic workup of varicosis. The present article discusses the use of preinter-ventional, intrainterventional and postinterventional duplex ultra-sound in endoluminal methods for the treatment of varices. It is a pre-requisite for the planning, implementation, and follow-up of this form of therapy.

Background Inflammatory processes of the venous wall in acute deep vein thrombosis (DVT) play a role in thrombus formation and resolution. However, direct evaluation of the perivascular inflammation is currently not feasible. Objective To assess perivascular perfusion in acute proximal DVT using contrast enhanced ultrasound (CEUS) reflecting perivenous inflammation and its association with systemic inflammatory markers in a single-centre, prospective observational study. Patients/Methods Twenty patients with proximal DVT underwent CEUS imaging in the thrombosed and contralateral popliteal vein at baseline and after 2 weeks and 3 months. Perfusion was quantified by measuring peak enhancement (PE) and wash-in rate (WiR) in a perivenous region after bolus injection of the contrast agent. High sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) were determined at the time of each CEUS imaging. Results PE and WiR were significantly higher in the thrombosed compared with the unaffected leg at baseline (1,007 vs. 34 au and 103 vs. 4 au/s) and 2-week follow-up (903 vs. 35 au and 70 vs. 4 au/s). Compared with baseline, PE and WiR in the thrombosed leg significantly decreased to 217 au and 18 au/s at 3-month follow-up. At baseline, hsCRP and IL-6 were elevated at 20.1 mg/mL and 8.2 pg/mL and decreased significantly to 2.8 mg/mL and 2.6 pg/mL at 2-week follow-up, remaining low after 3 months. There was a weak association between the level of inflammatory markers and the CEUS parameters at baseline on the thrombosed leg. Conclusion Elevated perivascular perfusion assessed by CEUS imaging is associated with the inflammatory response in acute DVT.

Abstract The modified Ottawa score (MOS) predicted venous thromboembolism (VTE) recurrence in a cohort of patients with cancer-associated thrombosis mainly managed on an outpatient basis. We aimed to assess the prognostic value of the MOS in hospitalized patients with cancer-associated thrombosis. In 383 hospitalized patients with cancer-associated VTE from the SWIss VTE Registry, 98 (25%) were classified as low risk, 175 (46%) as intermediate risk, and 110 (29%) as high risk for VTE recurrence based on the MOS. Clinical end points were recurrent VTE, fatal VTE, major bleeding, and overall mortality at 90 days. Overall, 179 (47%) patients were female, 172 (45%) had metastatic disease, and 72 (19%) prior VTE. The primary site of cancer was lung in 48 (13%) patients and breast in 43 (11%). According to the MOS, the rate of VTE recurrence was 4.1% for low, 6.3% intermediate, and 5.5% high risk (p = 0.75); the rate of fatal VTE was 0.8, 1.9, and 2.0% (p = 0.69); the rate of major bleeding was 3.1, 4.1, and 3.6% (p = 0.92); and the rate of death was 6.1, 12.0, and 28.2% (p < 0.001), respectively. None of the MOS items was associated with VTE recurrence: female gender hazard ratio (HR) 1.26 (95% confidence interval [CI], 0.53–2.96), lung cancer HR 1.17 (95% CI, 0.35–3.98), prior VTE HR 0.44 (95% CI, 0.10–1.91), breast cancer HR 0.83 (95% CI, 0.19–3.58), and absence of metastases HR 0.74 (95% CI, 0.31–1.74). In hospitalized patients with cancer-associated VTE, the MOS failed to predict VTE recurrence at 3 months but was associated with early mortality.

BackgroundThe association between cancer and venous thromboembolism (VTE) in producing adverse clinical outcomes requires further investigation.MethodsIn the Swiss Venous ThromboEmbolism Registry (SWIVTER), we compared adverse clinical outcomes between 493 patients with cancer-associated VTE and 1,569 VTE patients without cancer, and identified independent predictors of 90-day mortality.ResultsAmong cancer patients, 351 (71%) had active disease at the time of VTE diagnosis and 232 (47%) had metastatic disease. Cancer patients more frequently had asymptomatic VTE (13 vs. 4%; p<0.001), iliofemoral deep vein thrombosis (42 vs. 32%; p=0.017), and upper extremity deep vein thrombosis (16 vs. 7%; p<0.001). Cancer was associated with an increased risk of cumulative 90-day mortality (13.0 vs. 2.2%; hazard ratio [HR], 6.27; 95% confidence interval [CI], 4.13-9.50; p<0.001), recurrent VTE (4.7 vs. 2.3%; HR, 2.05; 95% CI, 1.21-3.45; p=0.007), and bleeding requiring medical attention (5.7 vs. 3.3%; HR, 1.80; 95% CI, 1.13-2.86; p=0.013). Among cancer patients, the strongest factor associated with mortality was metastatic disease (HR, 4.86; 95% CI, 2.68-8.81; p<0.001), whereas it was pulmonary embolism among noncancer patients (HR, 4.96; 95% CI, 1.50-16.45; p=0.009). Symptomatic as compared with asymptomatic VTE predicted neither mortality (12.6 vs. 15.9%; HR, 0.76; 95% CI, 0.39-1.49; p=0.42) nor recurrent VTE (4.7 vs. 4.8%; HR, 0.98; 95% CI, 0.29-3.31; p=0.98) in cancer patients.ConclusionIn SWIVTER, early mortality of cancer-associated VTE was mainly driven by the extent of cancer disease and not by VTE symptoms or severity.

Part one addressed the value of duplex ultrasound in the diagnostic workup of varicosis. The present article discusses the use of preinterventional, intrainterventional and postinterventional duplex ultrasound in endoluminal methods for the treatment of varices. It is a prerequisite for the planning, implementation, and follow-up of this form of therapy.

CME-Rheumatologie 8/AuflösungGelenkschmerzen bei Nikotinkonsum?Giorgio Tamborrini and Thomas BaldiGiorgio Tamborrini Ultraschall Zentrum Rheumatologie, c/o Bethesda Spital, BaselSearch for more papers by this author and Thomas Baldi Angiologie Universitätsspital BaselSearch for more papers by this authorPublished Online:March 23, 2016https://doi.org/10.1024/1661-8157/a002290PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInReddit SectionsMoreFiguresReferencesRelatedDetails Volume 105Issue 7März 2016ISSN: 1661-8157eISSN: 1661-8165 InformationPraxis (2016), 105, pp. 419-420 https://doi.org/10.1024/1661-8157/a002290.© 2016Hogrefe AGPDF download

CME-Rheumatologie 8: Gelenkschmerzen bei Nikotinkonsum?Giorgio Tamborrini and Thomas BaldiGiorgio TamborriniUltraschall Zentrum Rheumatologie, c/o Bethesda Spital, Basel and Thomas BaldiAngiologie Universitätsspital BaselPublished Online:March 16, 2016https://doi.org/10.1024/1661-8157/a002289PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInReddit SectionsMoreFiguresReferencesRelatedDetails Volume 105Issue 6März 2016ISSN: 1661-8157eISSN: 1661-8165 History Licenses & Copyright© 2016Hogrefe AGPDF download

Summary We investigated three-month clinical outcomes in patients with venous thromboembolism (VTE) treated with rivaroxaban or conventional anticoagulation in routine clinical practice. Between November 2012 and February 2015, 2,062 consecutive patients with VTE from 11 acute care hospitals in Switzerland were enrolled in the SWIss Venous ThromboEmbolism Registry (SWIVTER). Overall, 417 (20 %) patients were treated with rivaroxaban. In comparison to 1,645 patients on conventional anticoagulation, patients on rivaroxaban were younger (56 ± 18 vs. 65 ± 17 years; p<0.001), less often had pulmonary embolism (38 % vs 66 %; p<0.001), hypertension (26 % vs 41 %; p<0.001), cancer (10 % vs 28 %; p<0.001), congestive heart failure (10 % vs 17 %; p=0.001), diabetes (8 % vs 15 %; p<0.001), chronic lung disease (7 % vs 13 %; p=0.001), renal insufficiency (7 % vs 13 %; p=0.001), recent surgery (7 % vs 14 %; p<0.001), and acute coronary syndrome (1 % vs 4 %; p=0.009). VTE reperfusion therapy was more frequently used (28 % vs 9 %; p<0.001) and indefinite-duration anticoagulation treatment less often planned (26 % vs 39 %; p<0.001), respectively. In the propensity score-adjusted population, the risk of recurrent VTE was similar in patients on rivaroxaban vs conventional anticoagulation (1.2 % vs 2.1 %, hazard ratio [HR] 0.55, 95 % confidence interval [CI] 0.18–1.65; p=0.29); the risk of major bleeding was also similar, respectively (0.5 % vs 0.5 %, HR 1.00, 95 %CI 0.14–7.07; p=1.00). Conventional anticoagulation is still frequently used for the treatment of VTE, particularly in the elderly and those with comorbidities. Early clinical outcomes were comparable between propensity score-adjusted patient populations on rivaroxaban and conventional anticoagulation.

Contrast-enhanced ultrasound (CEUS) has emerged as a valuable imaging modality that complements and enhances standard vascular ultrasound imaging.Ultrasound contrast agents are gas-filled microbubbles that are injected intravenously and serve as intravascular tracers.Based on the properties to enhance and to quantify the macro-and microcirculation down to the capillary perfusion level in different vascular territories and organs, CEUS imaging has the potential to improve the diagnostic performance in the detection and characterisation of various vascular disorders reviewed in this article.In carotid atherosclerotic disease, CEUS imaging provides additional information on plaque vulnerability by illustrating the presence and extent of intraplaque neovascularisation.This new imaging modality may be helpful for further risk stratification of arteriosclerotic lesions and for detecting patients at risk for vascular events, eventually leading to more specific individually tailored therapeutic recommendations.CEUS imaging is also a helpful tool for the diagnosis and for monitoring of inflammatory vascular diseases.It increases the diagnostic performance of ultrasound in detecting inflammatory changes of the vessel wall such as hypervascularisation and hyperaemia.Changes in vessel wall enhancement may also reflect the response to antiinflammatory therapy.Moreover, CEUS imaging is also a valuable tool for the assessment of the microcirculation and the tissue perfusion in solid organs including native and transplanted kidneys.The technique provides more accurate information on perfusion deficits of the parenchyma in patients with kidney infarction, necrosis or graft dysfunction.CEUS also has great potential in the assessment of the microcirculation of the skeletal muscle, particularly in patients with peripheral artery disease or diabetic microangiopathy.In the future, the use of targeted on site microbubbles could further enhance and expand the diagnostic capabilities of current vascular ultrasound by assessing specific molecular processes that play a role in the pathophysiology of vascular diseases.Furthermore, ultrasound-directed, site-specific drug and gene delivery using microbubble contrast agents could gain great clinical value in the future.The combina-tion of CEUS for diagnosis and therapy will provide unique opportunities for vascular clinicians to image the microcirculation and directly treat vascular diseases.

Sir, In winter 2011 a 24-year-old Caucasian woman presented with a 3-day history of painful lesions on the fingertips (Figure 1(a)) and subungual haemorrhages (Figure 1(b) and (c)). She negated joint pain, skin rash, sicca or constitutional symptoms. There was no history of thrombosis or abortion. Six weeks earlier she was vaccinated against HBV. Routine lab, ESR (2mm/h) and urine sediment were normal. Pulse volume recording indicated normal peripheral perfusion and a cardiac or intravascular source of emboli was excluded. Capillary microscopy of the nail fold showed subungual bleeding (‘splinter’) (Figure 1(c)) but no other signs of collagen vascular disease (Figure 1(d)). Antinuclear antibodies (ANA) were slightly elevated with a titre of 1:80 (normal< 1:40) and anti-DNA antibodies were detectable at 59 IU/ml (normal< 10 IU/ml). Lupus anticoagulant was detectable using a DRVVT screening and confirmation test. Tests for complement consumption, anti-cardiolipin and anti-glycoprotein antibodies, rheumatic factor, HIV, HCV and cryoglobulinemia were all negative. Diagnosis of (secondary) antiphospholipid syndrome (APS), most likely on the basis of a systemic lupus erythematosus (SLE) predisposition, was made. Notably, the ACR SLE criteria were not fulfilled, but ANA, anti-DNA antibodies, and antiphospholipid antibodies can all occur years before definite diagnosis. Because of the absence of a severe thrombotic event, and since we expected the aetiology to be a minor arterial thrombotic occlusion, ASA 100mg once daily was preferred over oral anticoagulation in this young patient. The pain and the subungual haemorrhages resolved within a few days, strongly supporting ischemic microinfarction rather than vasculitic haemorrhage as the pathogenic mechanism leading to the symptoms. The positive lupus anticoagulant was confirmed on two occasions 18 months apart. Similarly, positive anti-DNA antibodies persisted on follow-up after 18 months at levels of 53–81 IU/ml. Furthermore, both splinter haemorrhages and the painful lesions on the fingertips reoccurred when ASA was transiently stopped after 12 months, suggesting a persistent underlying coagulopathy. However, during 2.5-year follow-up only mild intermittent arthralgia of the small finger joints, but no definite signs for SLE, occurred. Subungual splinter haemorrhages have been reported in APS but usually occur associated with severe thrombotic events and/or in clinically apparent SLE. In contrast, our case illustrates that this symptom may, however, represent the initial and isolated symptom of secondary APS. Previous studies reported that ASA was not effective in primary prevention of severe thrombotic events in patients with anti-phospholipid antibodies. Our case suggests, however, that it might be effective in treating and preventing reoccurrence of small arterial occlusion in secondary APS.

The use of contrast-enhanced ultrasound (CEUS) for vascular imaging indications has increased dramatically during the last decade. Ultrasound contrast agents are gas-filled micro-bubbles that are injected into the bloodstream and serve as strict intravascular reflectors of ultrasound waves. Numerous studies have addressed the potential clinical use of CEUS in different vascular fields including the carotid arteries, the abdominal aorta, renal arteries and the kidneys. In this review article we discuss the clinical value of contrast agents in vascular ultrasound by enhancing the vascular lumen, and more important, their role as a tool to deliver high resolution, real-time images of microvascular perfusion.Specifically, CEUS imaging of the carotid artery provides a novel, non-invasive method not only to improve the delineation of the vessel wall, but also for the assessment of the vasa vasorum and the ectopic vascularization of the atherosclerotic plaque (intraplaque neovascularization); probably providing a "window" to risk stratify atherosclerotic lesions and individuals by identifying "vulnerable" plaques prone to rupture causing vascular events.CEUS imaging has also emerged as a novel diagnostic tool in various aortic pathologies and particularly for the detection of endoleaks following endovascular treatment of abdominal aortic aneurysms. It is also a valuable tool for the assessment of the tissue perfusion in native and transplanted kidneys providing information on perfusion deficits of the parenchyma. Furthermore, a real-time CEUS method has recently been developed to assess the skeletal muscle microcirculation which could be used to study patients with peripheral arterial occlusive disease or diabetic microangiopathy. In the future, the use of targeted microbubbles could further enhance and expand the diagnostic capabilities of current vascular ultrasound imaging by detecting specific molecular processes that play a role in the pathophysiology of vascular disease.

OBJECTIVE:Contrast-enhanced ultrasound that is used to assess atherosclerotic carotid plaques improves visualization of vessel wall irregularities and provides direct visualization of intraplaque neovascularization. This article illustrates the use of contrast-enhanced ultrasound in the assessment of carotid atherosclerotic lesions.CONCLUSION:Contrast-enhanced ultrasound is a new, noninvasive, and safe procedure for imaging carotid atherosclerotic lesions. It is a valuable tool for evaluating the vulnerable plaque at risk for rupture and for evaluating both the development and severity of systemic atherosclerotic disease.

In patients with acute cancer-associated thrombosis, current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved. Among 1,247 patients with acute venous thromboembolism (VTE) enrolled in the prospective Swiss Venous Thromboembolism Registry (SWIVTER) II from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, 83 (26%) prior cancer surgery, and 63 (20%) recurrent VTE. Long-term anticoagulation treatment for >12 months was more often planned in patients with versus without cancer (47% vs. 19%; p<0.001), with recurrent cancer-associated versus first cancer-associated VTE (70% vs. 41%; p<0.001), and with metastatic versus non-metastatic cancer (59% vs. 31%; p<0.001). In patients with cancer, recurrent VTE (OR 3.46; 95%CI 1.83-6.53), metastatic disease (OR 3.04; 95%CI 1.86-4.97), and the absence of an acute infection (OR 3.55; 95%CI 1.65-7.65) were independently associated with the intention to maintain anticoagulation for >12 months. In conclusion, long-term anticoagulation treatment for more than 12 months was planned in less than half of the cancer patients with acute VTE. The low rates of long-term anticoagulation in cancer patients with a first episode of VTE and in patients with non-metastatic cancer require particular attention.

AIMS:Although acute venous thrombo-embolism (VTE) often afflicts patients with advanced age, the predictors of in-hospital mortality for elderly VTE patients are unknown. METHODS AND RESULTS:Among 1247 consecutive patients with acute VTE from the prospective SWIss Venous ThromboEmbolism Registry (SWIVTER), 644 (52%) were elderly (≥65 years of age). In comparison to younger patients, the elderly more often had pulmonary embolism (PE) (60 vs. 42%; P< 0.001), cancer (30 vs. 20%; P< 0.001), chronic lung disease (14 vs. 8%; P= 0.001), and congestive heart failure (12 vs. 2%; P< 0.001). Elderly VTE patients were more often hospitalized (75 vs. 52%; P< 0.001), and there was no difference in the use of thrombolysis, catheter intervention, or surgical embolectomy between the elderly and younger PE patients (5 vs. 6%; P= 0.54), despite a trend towards a higher rate of massive PE in the elderly (8 vs. 4%; P= 0.07). The overall in-hospital mortality rate was 6.6% in the elderly vs. 3.2% in the younger VTE patients (P= 0.033). Cancer was associated with in-hospital death both in the elderly [hazard ratio (HR) 4.91, 95% confidence interval (CI) 2.32-10.38; P< 0.001] and in the younger patients (HR 4.90, 95% CI 1.37-17.59; P= 0.015); massive PE was a predictor of in-hospital death in the elderly only (HR 3.77, 95% CI 1.63-8.74; P= 0.002). CONCLUSION:Elderly patients had more serious VTE than younger patients, and massive PE was particularly life-threatening in the elderly.

Summary A low simplified Pulmonary Embolism Severity Index (sPESI), defined as age ≤80 years and absence of systemic hypotension, tachycardia, hypoxia, cancer, heart failure, and lung disease, identifies low-risk patients with acute pulmonary embolism (PE). It is unknown whether cardiac troponin testing improves the prediction of clinical outcomes if the sPESI is not low. In the prospective Swiss Venous Thromboembolism Registry, 369 patients with acute PE and a troponin test (conventional troponin T or I, highly sensitive troponin T) were enrolled from 18 hospitals. A positive test result was defined as a troponin level above the manufacturers assay threshold. Among the 106 (29%) patients with low sPESI, the rate of mortality or PE recurrence at 30 days was 1.0%. Among the 263 (71%) patients with high sPESI, 177 (67%) were troponin-negative and 86 (33%) troponin-positive; the rate of mortality or PE recurrence at 30 days was 4.6% vs. 12.8% (p=0.015), respectively. Overall, risk assessment with a troponin test (hazard ratio [HR] 3.39, 95% confidence interval [CI] 1.38–8.37; p=0.008) maintained its prognostic value for mortality or PE recurrence when adjusted for sPESI (HR 5.80, 95%CI 0.76–44.10; p=0.09). The combination of sPESI with a troponin test resulted in a greater area under the receiver-operating characteristic curve (HR 0.72, 95% CI 0.63–0.81) than sPESI alone (HR 0.63, 95% CI 0.57–0.68) (p=0.023). In conclusion, although cardiac troponin testing may not be required in patients with a low sPESI, it adds prognostic value for early death and recurrence for patients with a high sPESI.

SummaryThree-month anticoagulation is recommended to treat provoked or first distal deep-vein thrombosis (DVT), and indefinite-duration anticoagulation should be considered for patients with unprovoked proximal, un-provoked recurrent, or cancer-associated DVT. In the prospective Out-patient Treatment of Deep Vein Thrombosis in Switzerland (OTIS-DVT) Registry of 502 patients with acute objectively confirmed lower extremity DVT (59% provoked or first distal DVT; 41% unprovoked proximal, unprovoked recurrent, or cancer-associated DVT) from 53 private practices and 11 hospitals, we investigated the planned duration of anticoagulation at the time of treatment initiation. The decision to administer limited-duration anticoagulation therapy was made in 343 (68%) patients with a median duration of 107 (interquartile range 91–182) days for provoked or first distal DVT, and 182 (interquartile range 111–184) days for unprovoked proximal, unprovoked recurrent, or cancer-associated DVT. Among patients with provoked or first distal DVT, anticoagulation was recommended for <3 months in 11%, ≥3 months in 63%, and for an indefinite period in 26%. Among patients with unprovoked proximal, unprovoked recurrent, or cancer-associated DVT, anticoagulation was recommended for <6 months in 22%, 6–12 months in 38%, and for an indefinite period in 40%. Overall, there was more frequent planning of indefinite-duration therapy from hospital physicians as compared with private practice physicians (39% vs. 28%; p=0.019). Considerable inconsistency in planning the duration of anticoagulation therapy mandates an improvement in risk stratification of outpatients with acute DVT.