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1.
Clin Res Cardiol ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32025793

RESUMO

BACKGROUND: Recent studies demonstrate an improved prognostic performance of the 2014 European Society of Cardiology (ESC) algorithm for risk stratification of patients with pulmonary embolism (PE) compared to the 2008 ESC algorithm. The modified FAST and Bova scores appear especially helpful to identify PE patients at intermediate-high risk. METHODS: We validated the prognostic performance of the modified FAST score compared to other scores for risk stratification in a post-hoc analysis of 868 normotensive PE patients included in the prospective Italian Pulmonary Embolism Registry. In-hospital adverse outcome was defined as PE-related death, mechanical ventilation, cardiopulmonary resuscitation or administration of catecholamines. RESULTS: Overall, 27 patients (3.1%) had an adverse outcome and 32 patients (3.7%) died. The rate of an adverse outcome was highest in the intermediate-high risk classes of the 2019 ESC algorithm (7.5%) and the modified FAST score (5.3%) while the Bova score failed to discriminate between intermediate-low and intermediate-high-risk patients. Patients classified as intermediate-high risk by the 2019 ESC algorithm (Odds Ratio [OR], 4.2 [95% CI, 1.9-9.0]) and modified FAST score (OR, 2.8 [1.3-6.2]) had a higher risk of an adverse outcome compared to patients classified by the Bova score (OR, 1.6 [0.7-3.7]). The c-index was higher for the 2019 ESC algorithm and the modified FAST score (AUC, 0.69 [0.58-0.79] and 0.67 [0.59-0.76]) compared to the Bova score (AUC, 0.64 [0.55-0.73]). CONCLUSIONS: The 2019 ESC algorithm provided the best prognostic performance, but also the modified FAST score accurately stratified normotensive PE patients in different risk classes while the Bova score failed to identify patients at highest risk.

2.
Thromb Res ; 185: 20-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734602

RESUMO

INTRODUCTION: Although a number of risk factors for chronic thromboembolic pulmonary hypertension (CTEPH) have been reported, the exact prevalence is controversial and varies between published cohorts. The aim of the present study was to investigate the prevalence of risk factors in operable CTEPH patients with special emphasis on thyroid disease and function. MATERIAL AND METHODS: Overall, 228 CTEPH patients (47.7% female; median age 63 [IQR 52-72] years) scheduled for pulmonary endarterectomy between 01/2014 and 12/2015 were studied. Prevalence of risk factors was assessed, and patients were classified according to their thyroid function based on laboratory measurements. RESULTS: As many as 86.0% of patients reported a history of pulmonary embolism (PE; of those, 24.5% were diagnosed with "acute" PE less than six months before the diagnosis of CTEPH), 80.7% of patients had a blood group non-0 and 24.1% of patients had known thyroid disease (of those, 78.2% hypothyroidism). Laboratory measurements revealed thyroid dysfunction in 10.5% of patients (of those, 54.8% had no known thyroid disease). Patients with hypothyroid function had higher WHO functional classes, NT-proBNP levels and a lower cardiac index compared to patients with euthyroid function. CONCLUSIONS: The prevalence of a history of PE and blood group non-0 was higher than previously reported. However, a relevant proportion of patients might have suffered from pre-existing CTEPH rather than acute PE. Thyroid disease and dysfunction were frequent and hypothyroid function associated with more severe disease.

4.
Clin Res Cardiol ; 109(1): 67-77, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31065790

RESUMO

BACKGROUND: Real-world data on the impact of advances in risk-adjusted management on the outcome of patients with pulmonary embolism (PE) are limited. METHODS: To investigate temporal trends in treatment, in-hospital adverse outcomes and 1-year mortality, we analysed data from 605 patients [median age, 70 years (IQR 56-77) years, 53% female] consecutively enrolled in a single-centre registry between 09/2008 and 08/2016. RESULTS: Over the 8-year period, more patients were classified to lower risk classes according to the European Society of Cardiology (ESC) 2014 guideline algorithm while the number of high-risk patients with out-of-hospital cardiac arrest (OHCA) increased. Although patients with OHCA had an exceptionally high in-hospital mortality rate of 59.3%, the rate of PE-related in-hospital adverse outcomes (12.2%) in the overall patient cohort remained stable over time. The rate of reperfusion treatment was 9.6% and tended to increase in high-risk patients. We observed a decrease in the median duration of in-hospital stay from 10 (IQR 6-14) to 7 (IQR 4-15) days, an increase of patients discharged early from 2.1 to 12.2% and an increase in the use of non-vitamin K-dependent oral anticoagulants (NOACs) from 12.6 to 57.2% in the last 2 years (09/2014-08/2016) compared to first 6 years (09/2008-08/2014). The 1-year mortality rate (16.9%) remained stable throughout the study period. CONCLUSION: In-hospital adverse outcomes and 1-year mortality remained stable despite more patients with OHCA, shorter in-hospital stays, more patients discharged early and a more frequent NOAC use.

5.
Eur Heart J ; 41(4): 509-518, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31120118

RESUMO

AIMS: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. METHODS AND RESULTS: We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%). CONCLUSION: Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.

6.
Eur Heart J ; 41(4): 522-529, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31102407

RESUMO

AIMS: Pulmonary embolism (PE) is the third most common cardiovascular cause of death; systemic thrombolysis is potentially lifesaving treatment in patients presenting with haemodynamic instability. We investigated trends in the use of systemic thrombolysis and the outcome of patients with acute PE. METHODS AND RESULTS: We analysed data on the characteristics, comorbidities, treatment, and in-hospital outcome of 885 806 PE patients in Germany between 2005 and 2015. Incidence of acute PE was 99/100 000 population/year and increased from 85/100 000 in 2005 to 109/100 000 in 2015 [ß 0.32 (0.26-0.38), P < 0.001]. During the same period, in-hospital case fatality rates decreased from 20.4% to 13.9% [ß -0.51 (-0.52 to -0.49), P < 0.001]. The overall proportion of patients treated with systemic thrombolysis increased from 3.1% in 2005 to 4.4% in 2015 [ß 0.28 (0.25-0.31), P < 0.001]. Thrombolysis was associated with lower in-hospital mortality rates in patients with haemodynamic instability, both in those with shock not necessitating cardiopulmonary resuscitation (CPR) or mechanical ventilation [odds ratio (OR) 0.42 (0.37-0.48), P < 0.001], and in those who underwent CPR [OR 0.92 (0.87-0.97), P = 0.002]. This association was independent from age, sex, and comorbidities. However, systemic thrombolysis was administered to only 23.1% of haemodynamically unstable patients. CONCLUSION: Although the proportion of PE patients treated with systemic thrombolysis increased slightly in Germany between 2005 and 2015, only the minority of haemodynamically unstable patients currently receive this treatment. In the nationwide inpatient cohort, thrombolytic therapy was associated with reduced in-hospital mortality rates in PE patients with shock, and also in those who underwent CPR.

7.
J Thromb Haemost ; 18(1): 151-161, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31479557

RESUMO

BACKGROUND: Women are more susceptible than men to several forms of pulmonary hypertension, but have better survival. Sparse data are available on chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: We investigated sex-specific differences in the clinical presentation of CTEPH, performance of pulmonary endarterectomy (PEA), and survival. RESULTS: Women constituted one-half of the study population of the European CTEPH registry (N = 679) and were characterized by a lower prevalence of some cardiovascular risk factors, including prior acute coronary syndrome, smoking habit, and chronic obstructive pulmonary disease, but more prevalent obesity, cancer, and thyroid diseases. The median age was 62 (interquartile ratio, 50-73) years in women and 63 (interquartile ratio, 53-70) in men. Women underwent PEA less often than men (54% vs 65%), especially at low-volume centers (48% vs 61%), and were exposed to fewer additional cardiac procedures, notably coronary artery bypass graft surgery (0.5% vs 9.5%). The prevalence of specific reasons for not being operated, including patient's refusal and the proportion of proximal vs distal lesions, did not differ between sexes. A total of 57 (17.0%) deaths in women and 70 (20.7%) in men were recorded over long-term follow-up. Female sex was positively associated with long-term survival (adjusted hazard ratio, 0.66; 95% confidence interval, 0.46-0.94). Short-term mortality was identical in the two groups. CONCLUSIONS: Women with CTEPH underwent PEA less frequently than men, especially at low-volume centers. Furthermore, they had a lower prevalence of cardiovascular risk factors and were less often exposed to additional cardiac surgery procedures. Women had better long-term survival.

9.
Lancet Respir Med ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31615719

RESUMO

BACKGROUND: European estimates of the burden imposed by pulmonary embolism are not available to this date. We aimed to assess pulmonary embolism-related mortality and time trends in the WHO European Region. METHODS: We analysed vital registration data from the WHO Mortality Database (2000-15) covering subregions of the WHO European Region: Eastern Europe, Northern Europe, Southern Europe, Western Europe, and Central Asia. Deaths were considered pulmonary embolism-related if International Classification of Disease-10 code for acute pulmonary embolism (I26) or any code for deep or superficial vein thrombosis was listed as the primary cause of death. We used locally estimated scatterplot smoothing weighted by size of the Member State population to calculate proportionate mortality and time trends in age-standardised mortality. FINDINGS: In the 3-year period between 2013 and 2015, an average of 38 929 pulmonary embolism-related deaths occurred annually in the 41 Member States with available data and a population of 650 950 921; among individuals aged 15-55 years, pulmonary embolism accounted for 8-13 per 1000 deaths in women and 2-7 per 1000 deaths in men. Between 2000 and 2015, age-standardised annual pulmonary embolism-related mortality rates decreased linearly from 12·8 (95% CI 11·4-14·2) to 6·5 (5·3-7·7) deaths per 100 000 population without substantial sex-specific differences. INTERPRETATION: The observed decreasing trends in pulmonary embolism-related mortality might reflect improved management of the disease, in line with case fatality data from cohort studies. Additional, or alternative, explanations might include the absence of a uniform case definition and changes in coding practices and performing autopsy. Pulmonary embolism still imposes a relevant medical and societal burden. Continuing efforts are warranted to improve awareness and implement effective preventive and therapeutic measures. FUNDING: German Federal Ministry of Education and Research.

12.
Res Pract Thromb Haemost ; 3(3): 364-371, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31294323

RESUMO

Introduction: VTE-BLEED is a validated score for identification of patients at increased risk of major bleeding during extended anticoagulation for venous thromboembolism (VTE). It is unknown whether VTE-BLEED high-risk patients also have an increased risk for recurrent VTE, which would limit the potential usefulness of the score. Methods: This was a post hoc analysis of the randomized, double-blind, placebo-controlled PADIS-PE trial that randomized patients with a first unprovoked pulmonary embolism (PE) initially treated during 6 months to receive an additional 18-month of warfarin vs. placebo. The primary outcome of this analysis was recurrent VTE during 2-year follow-up after anticoagulant discontinuation, that is, after the initial 6-month treatment in the placebo arm and after 24 months of anticoagulation in the active treatment arm. This rate, adjusted for study treatment allocation, was compared between patients in the high- vs. low-risk VTE-BLEED group. Results: In complete case analysis (n = 308; 82.4% of total population), 89 (28.9%) patients were classified as high risk; 44 VTE events occurred after anticoagulant discontinuation during 668 patient-years. The cumulative incidence of recurrent VTE was 16.4% (95% confidence interval [CI], 10.0%-26.1%; 14 events) and 14.6% (95% CI, 10.4%-20.3%; 30 events) in the high-risk and low-risk VTE-BLEED groups, respectively, for an adjusted hazard ratio of 1.16 (95% CI, 0.62-2.19). Conclusion: In this study, patients with unprovoked PE classified at high risk of major bleeding by VTE-BLEED did not have a higher incidence of recurrent VTE after cessation of anticoagulant therapy, supporting the potential yield of the score for making management decisions on the optimal duration of anticoagulant therapy.

13.
J Thromb Haemost ; 17(11): 1923-1934, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31344319

RESUMO

BACKGROUND: While the importance of patients' quality of life (QoL) in chronic cardiac or pulmonary disease is uncontroversial, the burden of an acute pulmonary embolism (PE) on QoL has received little attention thus far. OBJECTIVES: We aimed to validate the German PEmb-QoL questionnaire, identify associations between QoL and clinical/functional parameters, and investigate the prognostic relevance of QoL for long-term survival in survivors of an acute PE episode. PATIENTS/METHODS: Patients were invited for a clinical follow-up visit including assessment of QoL using the German PEmb-QoL questionnaire 6 months after an objectively confirmed PE at a single center. Internal consistency reliability, construct-related validity, and regressions between PEmb-QoL and clinical patient-characteristics were assessed using standard scale construction techniques. RESULTS: Overall, 101 patients [median age, 69 ([interquartile range] IQR 57-75) years; women, 48.5%] were examined 208 (IQR 185-242) days after PE. Internal consistency reliability and construct-related validity of the PEmb-QoL questionnaire were acceptable. As many as 47.0% of patients reported dyspnea, 27.5% had right ventricular (RV) dysfunction on transthoracic echocardiography (TTE), and 25.3% were diagnosed with post-PE impairment (PPEI) at 6-month follow-up. Furthermore, 15.9% of patients were diagnosed with depression 6 months after an acute PE. The QoL was affected by dyspnea, preexisting pulmonary disease, and PPEI, and a reduced QoL was associated with an increased risk for long-term mortality after an observation period of 3.6 years. CONCLUSIONS: The German PEmb-QoL questionnaire is a reliable instrument for assessing QoL 6 months after PE. The QoL was affected by dyspnea, preexisting pulmonary disease, and PPEI and was associated with long-term mortality.

14.
Thromb Haemost ; 119(8): 1332-1346, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31183846

RESUMO

BACKGROUND: Inflammation and incomplete thrombus resolution leading to obstructive fibrotic remodelling are considered critical mechanisms for the development of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE). Osteopontin (OPN) is involved in a variety of biological processes including inflammation and tissue fibrosis. METHODS: OPN plasma concentrations were measured in 70 CTEPH and 119 PE patients. Tissue material from 6 CTEPH patients removed during pulmonary endarterectomy and murine venous thrombi induced by subtotal ligation of the inferior vena cava in C57BL/6 mice were analysed by (immuno)histochemistry. RESULTS: CTEPH patients had higher OPN plasma concentrations (median, 106.9 [interquartile range, 75.6-155.9]) compared to PE patients (90.4 [53.3-123.9] ng/mL, p = 0.001). OPN- and matrix metalloproteinase (MMP)-9-positive cells were predominantly present in myofibroblast-rich and profibrotic areas of CTEPH tissue material. Early stages of murine thrombus resolution were characterised by high numbers of OPN- and MMP-2-positive cells while OPN was almost absent in fresh thrombi of CTEPH tissue material. PE patients with OPN plasma concentrations of < 55 ng/mL had a 15.2-fold (95% confidence interval, 1.7-135.5, p = 0.015) increased risk for a diagnosis of CTEPH during follow-up. CONCLUSION: The results of the present observational translational study point to a possible involvement of OPN in the pathogenesis of CTEPH by affecting early inflammatory and late fibrotic processes.

15.
Eur Heart J ; 40(23): 1827-1829, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31199495
16.
TH Open ; 3(1): e58-e63, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31249983

RESUMO

Background It remains unclear whether the distal location of deep vein thrombosis (DVT) is independently associated with a lower risk of recurrence in all patients, or represents a marker of the presence and severity of provoking factors for venous thromboembolism (VTE). Methods We investigated the impact of distal (vs. proximal) DVT location on the risk of developing symptomatic, objectively confirmed recurrent VTE in 831 patients with a first acute symptomatic DVT not associated with pulmonary embolism (PE), who were stratified by the presence of transient or persistent risk factors at baseline. The primary outcome was symptomatic, objectively diagnosed recurrent VTE, including proximal DVT and PE. Results A total of 205 (24.7%) patients presented with a transient risk factor, 189 (22.7%) with a minor persistent risk factor, 202 (24.3%) with unprovoked DVT, and 235 (28.3%) with cancer-associated DVT. One-hundred twenty-five patients (15.0%) experienced recurrent DVT or PE. The largest relative difference between patients with distal (vs. proximal) DVT was observed in the absence of identifiable risk factors (adjusted hazard ratio [aHR]: 0.11; 95% CI [confidence interval]: 0.03-0.45). In patients with cancer, distal and proximal DVT had a comparable risk of recurrence (aHR: 0.70; 95% CI: 0.28-1.78]). Conclusions The distal (vs. proximal) location of first acute symptomatic DVT represented, in the absence of any identifiable transient or persistent risk factors, a favorable prognostic factor for recurrence. In contrast, the prognostic impact of DVT location was weaker if persistent provoking risk factors for VTE were present, notably cancer.

17.
Thromb Res ; 178: 173-181, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31039477

RESUMO

INTRODUCTION: Sex-specific differences regarding risk factors, symptoms and prognosis have been reported for several cardiovascular diseases. For patients with pulmonary embolism (PE), sex-specific data are limited and inconsistent. We aimed to investigate sex-specific differences in PE. MATERIALS AND METHODS: Over a 10-year period (01/2003-09/2013), patients with confirmed PE were enrolled in a prospective single-centre cohort study. RESULTS: We prospectively examined 569 PE patients (55.9% women). Men more often had cancer (20.7% vs. 13.5%, p = 0.024) and unprovoked PE (61.0% vs. 47.5%, p = 0.001) while women more frequently presented with risk factors for venous thromboembolism such as older age (median, 71 [IQR, 55-79] vs. 67 [53-75] years, p = 0.008), surgery/trauma/immobilisation (38.4% vs. 29.5%, p = 0.026) and sex-hormone therapy (14.8% vs. 0.8%, p < 0.001). Overall, 84 patients (14.8%) had an adverse 30-day outcome and 43 (7.6%) died within 30 days; outcomes did not differ between males and females and were not influenced by the patients' sex. Risk stratification markers and models such as right ventricular dysfunction on TTE/CT, cardiac troponin, sPESI, Bova score and 2014 ESC guidelines algorithm predicted adverse outcome in normotensive female patients only, while tachycardia, hypoxia, NT-proBNP and modified FAST score were able to predict an adverse outcome in both sexes. Using sex-specific biomarker cut-off values, the 2014 ESC guidelines algorithm was able to predict adverse outcome in both sexes. CONCLUSIONS: The 30-day adverse outcomes did not differ between male and female PE patients and were not influenced by the patients' sex despite sex-specific differences in the prognostic performance of risk stratification markers/models.

18.
Int J Cardiol ; 290: 144-149, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30917899

RESUMO

BACKGROUND: Assessment of bleeding risk in patients with pulmonary embolism (PE) is challenging. Recently, the VTE-BLEED score was shown to predict major bleeding. Therefore, we aimed to investigate the VTE-BLEED score and assess the prognostic impact of major bleeding in a real-world cohort of PE patients. METHODS: Consecutive PE patients included in a prospective single-center cohort study between 09/2008 and 11/2016 were eligible for analysis; patients treated with thrombolysis were excluded. The VTE-BLEED was calculated post-hoc; in-hospital major bleeding was defined using the ISTH definition. RESULTS: Overall, 522 patients (median age 69, IQR 56-78 years; 53% female) were included in the present analysis; major bleeding occurred in 18 (3.5%) patients. A VTE-BLEED score ≥2 points identified patients at high-risk for major bleeding (OR 3.7, 95% CI 1.1-13.0, sensitivity 83%, specificity 42%). Additionally, a GFR <30 ml/min/1.73 m2 (OR 6.0, 95% CI 1.8-19.8) and previous surgery (OR 3.6, 95% CI 1.4-9.3) were associated with major bleeding. A less frequent use of unfractionated heparin as initial treatment was associated with a decrease of major bleeding over time. Major bleeding was identified as strong predictor of in-hospital (OR 7.7, 95% CI 2.3-25.8) and 1-year mortality (HR 3.6, 95% CI 2.0-6.6), especially in normotensive patients (OR 12.1, 95% CI 3.5-43.0 and HR 6.0, 95% CI 2.9-12.6, respectively). CONCLUSIONS: In a real-world cohort, the VTE-BLEED score identified PE patients at risk for in-hospital major bleeding. However, for assessment of bleeding risk, renal function and previous surgery should be considered. Major bleeding emerged as strong predictor of in-hospital and 1-year mortality.

19.
Circulation ; 139(17): 2032-2048, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30717607

RESUMO

BACKGROUND: Intraplaque hemorrhage promotes atherosclerosis progression, and erythrocytes may contribute to this process. In this study we examined the effects of red blood cells on smooth muscle cell mineralization and vascular calcification and the possible mechanisms involved. METHODS: Erythrocytes were isolated from human and murine whole blood. Intact and lysed erythrocytes and their membrane fraction or specific erythrocyte components were examined in vitro using diverse calcification assays, ex vivo by using the murine aortic ring calcification model, and in vivo after murine erythrocyte membrane injection into neointimal lesions of hypercholesterolemic apolipoprotein E-deficient mice. Vascular tissues (aortic valves, atherosclerotic carotid artery specimens, abdominal aortic aneurysms) were obtained from patients undergoing surgery. RESULTS: The membrane fraction of lysed, but not intact human erythrocytes promoted mineralization of human arterial smooth muscle cells in culture, as shown by Alizarin red and van Kossa stain and increased alkaline phosphatase activity, and by increased expression of osteoblast-specific transcription factors (eg, runt-related transcription factor 2, osterix) and differentiation markers (eg, osteopontin, osteocalcin, and osterix). Erythrocyte membranes dose-dependently enhanced calcification in murine aortic rings, and extravasated CD235a-positive erythrocytes or Perl iron-positive signals colocalized with calcified areas or osteoblast-like cells in human vascular lesions. Mechanistically, the osteoinductive activity of lysed erythrocytes was localized to their membrane fraction, did not involve membrane lipids, heme, or iron, and was enhanced after removal of the nitric oxide (NO) scavenger hemoglobin. Lysed erythrocyte membranes enhanced calcification to a similar extent as the NO donor diethylenetriamine-NO, and their osteoinductive effects could be further augmented by arginase-1 inhibition (indirectly increasing NO bioavailability). However, the osteoinductive effects of erythrocyte membranes were reduced in human arterial smooth muscle cells treated with the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide or following inhibition of NO synthase or the NO receptor soluble guanylate cyclase. Erythrocytes isolated from endothelial NO synthase-deficient mice exhibited a reduced potency to promote calcification in the aortic ring assay and after injection into murine vascular lesions. CONCLUSIONS: Our findings in cells, genetically modified mice, and human vascular specimens suggest that intraplaque hemorrhage with erythrocyte extravasation and lysis promotes osteoblastic differentiation of smooth muscle cells and vascular lesion calcification, and also support a role for erythrocyte-derived NO.

20.
Hamostaseologie ; 39(2): 117-127, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30336497

RESUMO

Acute pulmonary embolism (PE) contributes significantly to the global burden of cardiovascular disease. The severity of the acute PE event determines the expected estimated risk of early death. This risk is influenced by the degree of dysfunction of the right ventricle (RV), as assessed by the presence of acute RV pressure overload on imaging and/or elevated cardiac biomarkers, and by demographic and clinical factors, including relevant comorbidities. Haemodynamic instability and cardiogenic shock is at the top of the PE severity spectrum, as it represents the most extreme manifestation of RV failure and a key determinant of poor prognosis. Ideally, risk-adjusted treatment should implement: (1) optimized timing and regimens of reperfusion therapy for unstable patients; (2) early discharge and continuation of anticoagulation treatment at home (low-risk PE); or (3) hospital admission and clinical/haemodynamic monitoring in patients at intermediate risk. The challenge is now to provide the basis for a comprehensive personalized, risk-adjusted care for patients with acute PE. The aim of the integrated academic clinical trial programme of the Center for Thrombosis and Hemostasis at the University of Mainz is to develop and prospectively validate, in multinational studies, strategies for reperfusion and anticoagulant treatment of acute PE across the entire spectrum of early risk as well as clinical pathways for post-PE patient care and follow-up.


Assuntos
Ensaios Clínicos como Assunto , Medicina de Precisão/métodos , Embolia Pulmonar/terapia , Análise Custo-Benefício , Humanos , Medicina de Precisão/economia , Risco , Resultado do Tratamento
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