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2.
Eur J Intern Med ; 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32184031

RESUMO

BACKGROUND: The percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) remains debated. Therefore the aim of this large-scale observational multi-center registry was to compare the long-term outcome of CTO patients undergoing different therapeutic approaches comparing successful CTO revascularization either by PCI or coronary artery bypass graft (CABG), failed CTO-PCI and optimal medical therapy (OMT) alone. METHODS AND RESULTS: A total of 6630 CTO patients were enrolled from two high-volume centers to compare different treatment strategies. All procedures were performed by high-volume CTO operators in tertiary university hospital. Successful CTO-PCI was performed in 3906 patients, failed CTO-PCI in 1479 patients, 412 patients underwent CABG surgery and 833 patients were treated with OMT. During the 5-year follow-up period, 1019 (15%) patients died. Kaplan-Meier analysis unveiled a significantly improved long-term outcome for CTO patients undergoing revascularization either by PCI or by CABG compared to patients with failed CTO-PCI or OMT alone (log-rank P < 0.001). In the multivariate Cox-regression analysis successful CTO-PCI was associated with significantly improved long-term outcome compared to patients under OMT (adj. HR 0.39, 95%CI 0.33-0.45, P < 0.001) or CABG (adj. HR 0.68, 95%CI 0.53-0.86, P = 0.002) independent of clinical confounders encompassing age, BMI, diabetes, kidney function and left ventricular function. CONCLUSIONS: This study showed an improved long-term outcome for CTO revascularization compared to optimal medical therapy, independent from revascularization mode, with the highest survival rate in patients undergoing successful CTO-PCI.

3.
J Heart Lung Transplant ; 39(4): 300-309, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32061506

RESUMO

BACKGROUND: Approaches to risk assessment in pulmonary arterial hypertension (PAH) include the noninvasive French risk assessment approach (number of low-risk criteria based on the European Society of Cardiology and European Respiratory Society guidelines) and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) 2.0 risk calculator. The prognostic and predictive value of these methods for morbidity/mortality was evaluated in the predominantly prevalent population of GRIPHON, the largest randomized controlled trial in PAH. METHODS: GRIPHON randomized 1,156 patients with PAH to selexipag or placebo. Post-hoc analyses were performed on the primary composite end-point of morbidity/mortality by the number of low-risk criteria (World Health Organization functional class I-II; 6-minute walk distance >440 m; N-terminal pro-brain natriuretic peptide <300 ng/liter) and REVEAL 2.0 risk category. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazard models. RESULTS: Both the number of low-risk criteria and the REVEAL 2.0 risk category were prognostic for morbidity/mortality at baseline and any time-point during the study. Patients with 3 low-risk criteria at baseline had a 94% reduced risk of morbidity/mortality compared to patients with 0 low-risk criteria and were all categorized as low-risk by REVEAL 2.0. The treatment effect of selexipag on morbidity/mortality was consistent irrespective of the number of low-risk criteria or the REVEAL 2.0 risk category at any time-point during the study. Selexipag-treated patients were more likely to increase their number of low-risk criteria from baseline to week 26 than placebo-treated patients (odds ratio 1.69, p = 0.0002); similar results were observed for REVEAL 2.0 risk score. CONCLUSIONS: These results support the association between risk profile and long-term outcome and suggest that selexipag treatment may improve risk profile.

4.
Cardiovasc Drugs Ther ; 34(1): 53-63, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32062795

RESUMO

PURPOSE: Since ticagrelor inhibits the cellular uptake of adenosine, thereby increasing extracellular adenosine concentration and biological activity, we hypothesized that ticagrelor has adenosine-dependent antiplatelet properties. In the current study, we compared the effects of ticagrelor and prasugrel on platelet activation in acute coronary syndrome (ACS). METHODS: Platelet surface expression of P-selectin and activated glycoprotein (GP) IIb/IIIa in response to adenosine diphosphate (ADP), the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, the TLR-4 agonist lipopolysaccharide (LPS), the protease-activated receptor (PAR)-1 agonist SFLLRN, and the PAR-4 agonist AYPGKF were measured by flow cytometry in blood from 80 ticagrelor- and 80 prasugrel-treated ACS patients on day 3 after percutaneous coronary intervention. Residual platelet aggregation to arachidonic acid (AA) and ADP were assessed by multiple electrode aggregometry and light transmission aggregometry. RESULTS: ADP-induced platelet activation and aggregation, and AA-induced platelet aggregation were similar in patients on ticagrelor and prasugrel, respectively (all p ≥ 0.3). Further, LPS-induced platelet surface expression of P-selectin and activated GPIIb/IIIa did not differ significantly between ticagrelor- and prasugrel-treated patients (both p > 0.4). In contrast, Pam3CSK4-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly lower in ticagrelor-treated patients (both p ≤ 0.005). Moreover, SFLLRN-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly less pronounced in patients on ticagrelor therapy compared to prasugrel-treated patients (both p < 0.03). Finally, PAR-4 mediated platelet activation as assessed by platelet surface expression of activated GPIIb/IIIa following stimulation with AYPGKF was significantly lower in patients receiving ticagrelor (p = 0.02). CONCLUSION: Ticagrelor inhibits TLR-1/2 and PAR mediated platelet activation in ACS patients more strongly than prasugrel.

5.
Circulation ; 141(5): 376-386, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31896275

RESUMO

BACKGROUND: Pulmonary endarterectomy (PEA) is the gold standard treatment for patients with operable chronic thromboembolic pulmonary hypertension. However, persistent pulmonary hypertension (PH) after PEA remains a major determinant of poor prognosis. A concomitant small-vessel arteriopathy in addition to major pulmonary artery obstruction has been suggested to play an important role in the development of persistent PH and survival after PEA. One of the greatest unmet needs in the current preoperative evaluation is to assess the presence and severity of small-vessel arteriopathy. Using the pulmonary artery occlusion technique, we sought to assess the presence and degree of small-vessel disease in patients with chronic thromboembolic pulmonary hypertension undergoing PEA to predict postoperative outcome before surgery. METHODS: Based on pulmonary artery occlusion waveforms yielding an estimate of the effective capillary pressure, we partitioned pulmonary vascular resistance in larger arterial (upstream resistance [Rup]) and small arterial plus venous components (downstream resistance) in 90 patients before PEA. For validation, lung wedge biopsies were taken from nonobstructed and obstructed lung territories during PEA in 49 cases. Biopsy sites were chosen according to the pulmonary angiogram still frames that were mounted in the operating room. All vessels per specimen were measured in each patient. Percent media (%MT; arteries) and intima thickness (%IT; arteries, veins, and indeterminate vessels) were calculated relative to external vessel diameter. RESULTS: Decreased Rup was an independent predictor of persistent PH (odds ratio per 10%, 0.40 [95% CI, 0.23-0.69]; P=0.001) and survival (hazard ratio per 10%, 0.03 [95% CI, 0.00-0.33]; p=0.004). Arterial %MT and %IT of nonobstructed lung territories and venous %IT of obstructed lung territories were significantly increased in patients with persistent PH and nonsurvivors. Rup correlated inversely with %MT (r=-0.72, P<0.001) and %IT (r=-0.62, P<0.001) of arteries from nonobstructed lung territories and with %IT (r=-0.44, P=0.024) of veins from obstructed lung territories. Receiver operating characteristic analysis disclosed that Rup <66% predicted persistent PH after PEA, whereas Rup <60% identified patients with poor prognosis after PEA. CONCLUSIONS: Pulmonary artery occlusion waveform analysis with estimation of Rup seems to be a valuable technique for assessing the degree of small-vessel disease and postoperative outcome after PEA in chronic thromboembolic pulmonary hypertension.

6.
Wien Klin Wochenschr ; 132(3-4): 69-72, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31549230

RESUMO

Cardiovascular diseases during pregnancy are the most common causes of pregnancy-associated mortality.Vaginal delivery is the preferred mode of birth in the majority of pregnancies.It is recommended that patients with modified World Health Organization (mWHO) class IV risk are counselled against pregnancy.Patients carrying mWHO II-III, III, and class IV risks should undergo prepregnancy counselling by a multidisciplinary pregnancy heart team to determine a delivery plan and define postpartum care.Specific medications should not be principally withheld in pregnancy but the risk-benefit ratio should be carefully evaluated prior to administration.Beta blockers are recommended during and after pregnancy for congenital long QT syndrome and catecholaminergic polymorphic ventricular tachycardia.Low molecular weight heparin is the ideal substance for prophylaxis and treatment of venous thromboembolism in pregnancy under weekly monitoring of anti-factor Xa activity.

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.

8.
Chest ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31738929

RESUMO

BACKGROUND: Treatment of pulmonary arterial hypertension (PAH) has evolved substantially over the past two decades and varies according to etiology, functional class (FC), hemodynamic parameters, and other clinical factors. Current guidelines do not provide definitive recommendations regarding the use of oral prostacyclin pathway agents (PPAs) in PAH. To provide guidance on the use of these agents, an expert panel was convened to develop consensus statements for the initiation of oral PPAs in adults with PAH. METHODS: A systematic literature search was conducted using MEDLINE. The established RAND/University of California Los Angeles appropriateness method, which incorporates the Delphi method and the nominal group technique, was used to create consensus statements. Idiopathic, heritable, repaired congenital heart defect, and drug- or toxin-induced PAH (IPAH+) was considered as one etiologic grouping. The process was focused on the use of oral treprostinil or selexipag in patients with IPAH+ or connective tissue disease-associated PAH and FC II or III symptoms receiving background dual endothelin receptor antagonist/phosphodiesterase type 5 inhibitor therapy. RESULTS: The panel developed 14 consensus statements regarding the appropriate use of oral PPAs in the target population. The panel identified 13 clinical scenarios in which selexipag may be considered as a treatment option. CONCLUSIONS: The paucity of clinical evidence overall, and particularly from randomized trials in this setting, creates a gap in knowledge. These consensus statements are intended to aid physicians in navigating treatment options and using oral PPAs in the most appropriate manner in patients with PAH.

9.
Sci Rep ; 9(1): 16304, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704966

RESUMO

Neutrophils release their chromatin into the extracellular space upon activation. These web-like structures are called neutrophil extracellular traps (NETs) and have potent prothrombotic and proinflammatory properties. In ST-elevation myocardial infarction (STEMI), NETs correlate with increased infarct size. The interplay of neutrophils and monocytes impacts cardiac remodeling. Monocyte subsets are classified as classical, intermediate and non-classical monocytes. In the present study, in vitro stimulation with NETs led to an increase of intermediate monocytes and reduced expression of CX3CR1 in all subsets. Intermediate monocytes have been associated with poor outcome, while non-classical CX3CR1-positive monocytes could have reparative function after STEMI. We characterized monocyte subsets and NET markers at the culprit lesion site of STEMI patients (n = 91). NET surrogate markers were increased and correlated with larger infarct size and with fewer non-classical monocytes. Intermediate and especially non-classical monocytes were increased at the culprit site compared to the femoral site. Low CX3CR1 expression of monocytes correlated with high NET markers and increased infarct size. In this translational system, causality cannot be proven. However, our data suggest that NETs interfere with monocytic differentiation and receptor expression, presumably promoting a subset shift at the culprit lesion site. Reduced monocyte CX3CR1 expression may compromise myocardial salvage.

12.
Res Pract Thromb Haemost ; 3(3): 383-390, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31294325

RESUMO

Background: Despite the increasing use of potent P2Y12 inhibitors, further atherothrombotic events still impair the prognosis of many acute coronary syndrome (ACS) patients. This may in part be attributable to intact platelet aggregation via the human thrombin receptors protease-activated receptor (PAR)-1 and PAR-4. Objective: We studied PAR mediated platelet aggregation in ACS patients following percutaneous coronary intervention (PCI) with stent implantation in a cross-sectional study. Methods: Platelet aggregation to ADP as well as to the PAR-1 agonist SFLLRN and the PAR-4 agonist AYPGKF was assessed by multiple electrode aggregometry in 194 ACS patients on dual antiplatelet therapy with aspirin and either prasugrel (n = 114) or ticagrelor (n = 80) 3 days after PCI. Results: Based on the consensus cutoff value, high on-treatment residual platelet reactivity to ADP (HRPR ADP) was observed in only 2 prasugrel-treated patients. Both patients with HRPR ADP had also a normal response to SFLLRN and AYPGKF. Among the 112 prasugrel-treated patients with adequate P2Y12 inhibition, 50 patients (45%) still had a normal response to SFLLRN, and 70 patients (63%) still had a normal response to AYPGKF. Among the 80 ticagrelor-treated patients with adequate P2Y12 inhibition, 25 patients (31%) still had a normal response to SFLLRN, and 50 (63%) still had a normal response to AYPGKF. Conclusion: Normal platelet aggregation via PAR-1 and PAR-4 is preserved in many patients with adequate P2Y12 inhibition by prasugrel and ticagrelor. The present findings may at least in part explain adverse ischemic events despite potent P2Y12 inhibition.

13.
Dtsch Med Wochenschr ; 144(19): 1367-1372, 2019 09.
Artigo em Alemão | MEDLINE | ID: mdl-31277079

RESUMO

The ESC/ERS guidelines (published at the end of 2015) and other international recommendations defined pulmonary hypertension (PH) by an invasively measured mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg at rest. At the 6th World Symposium on Pulmonary Hypertension in Nice a modification of this hemodynamic definition in the sense of lowering the threshold to > 20 mmHg was proposed. A pulmonary vascular resistance (PVR) ≥ 3 Wood units (WU) is additionally required for the diagnosis of pre-capillary PH. This modification must be critically reviewed with regard to the underlying rationale and possible consequences. Therefore, a detailed explanation is required. In particular, it must be made clear that this change currently has no influence on the evidence-based and approval-compliant prescription of drugs for the targeted therapy of pulmonary arterial hypertension (PAH).


Assuntos
Hemodinâmica/fisiologia , Hipertensão Pulmonar , Anti-Hipertensivos/uso terapêutico , Cardiologia/organização & administração , Europa (Continente) , Humanos , Hipertensão Pulmonar/classificação , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Guias de Prática Clínica como Assunto , Pneumologia/organização & administração , Resistência Vascular
14.
Basic Res Cardiol ; 114(5): 33, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31312919

RESUMO

Leukocyte-mediated inflammation is central in atherothrombosis and ST-segment elevation myocardial infarction (STEMI). Neutrophil extracellular traps (NETs) have been shown to enhance atherothrombosis and stimulate fibroblast function. We analyzed the effects of NETs on cardiac remodeling after STEMI. We measured double-stranded (ds)DNA and citrullinated histone H3 (citH3) as NET surrogate markers in human culprit site and femoral blood collected during primary percutaneous coronary intervention (n = 50). Fibrocytes were characterized in whole blood by flow cytometry, and in culprit site thrombi and myocardium by immunofluorescence. To investigate mechanisms of fibrocyte activation, isolated NETs were used to induce fibrocyte responses in vitro. Enzymatic infarct size was assessed using creatine-phosphokinase isoform MB area under the curve. Left ventricular function was measured by transthoracic echocardiography. NET surrogate markers were increased at the culprit site compared to the femoral site and were positively correlated with infarct size and left ventricular dysfunction at follow-up. In vitro, NETs promoted fibrocyte differentiation from monocytes and induced fibrocyte activation. Highly activated fibrocytes accumulated at the culprit site and in the infarct transition zone. Our data suggest that NETs might be important mediators of fibrotic remodeling after STEMI, possibly by stimulating fibrocytes.


Assuntos
Armadilhas Extracelulares , Fibroblastos/patologia , Leucócitos/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Remodelação Ventricular/fisiologia , Adulto , Idoso , Feminino , Fibrose/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio com Supradesnível do Segmento ST/imunologia , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia
16.
J Thorac Cardiovasc Surg ; 158(2): 604-614.e2, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31084984

RESUMO

OBJECTIVE: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by one or more of the following features: intraluminal thrombus organization, fibrous stenosis, and complete obliteration of major pulmonary arteries, amenable to significant improvement by pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty, and medical treatments with vasodilators. Because treatment practices and outcomes differ in Europe versus Japan, we hypothesized that population-based characteristics of pulmonary vascular phenotypes may exist in Austria compared with Japan. The objectives of this study were to analyze clinical characteristics, hemodynamics, and PEA specimens in consecutive patients with CTEPH undergoing PEA in Austria and Japan. METHODS: Clinical features, hemodynamics, and PEA specimens were collected and analyzed in patients with CTEPH undergoing PEA, and clinical features and hemodynamics were collected and analyzed in patients with not-operated CTEPH and in patients with nonthromboembolic pulmonary arterial hypertension. RESULTS: Apart from key differences between Austrian and Japanese patients regarding body size, lung function vital capacity, cardiac output, and serum high-density lipoprotein levels, Austrian patients were more likely to be obese, have greater hematocrits and greater white blood cells counts, greater C-reactive protein levels, and significantly elevated serum myeloperoxidase levels compared with Japanese patients with CTEPH. Analysis of PEA specimens demonstrated more proximal thrombus and more fresh red thrombus components in Austrian patients. CONCLUSIONS: This study documents an inflammatory thrombotic phenotype in Austrian compared with Japanese patients with CTEPH that may be a determinant of differential treatment outcomes.


Assuntos
Hipertensão Pulmonar/etiologia , Embolia Pulmonar/complicações , Adulto , Idoso , Áustria , Doença Crônica , Endarterectomia , Feminino , Hemodinâmica , Humanos , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/cirurgia , Japão , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/patologia , Embolia Pulmonar/fisiopatologia , Embolia Pulmonar/cirurgia
17.
J Thromb Haemost ; 17(8): 1335-1344, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31099477

RESUMO

BACKGROUND: Patients with cancer are at risk of developing arterial thromboembolism (ATE). With the prevalence of cancer and cardiovascular diseases on the rise, the identification of risk factors for ATE in patients with cancer is of emerging importance. OBJECTIVES: As data on the association of potential biomarkers with risk of ATE in patients with cancer are scarce, we conducted a cohort study with the aim to identify blood-based biomarkers for ATE risk prediction in patients with cancer. PATIENTS/METHODS: Overall, 1883 patients with newly diagnosed cancer or progressive disease after complete or partial remission were included and followed for 2 years. Venous blood was drawn at study inclusion for measurement of complete blood count parameters, total cholesterol, d-dimer, and soluble P-selectin (sP-selectin) levels. RESULTS: The 2-year cumulative incidence of ATE was 2.5%. In univariable analysis, red cell distribution width (subdistribution hazard ratio (SHR) per doubling: 4.4, 95% CI: 1.4-14.1), leukocyte count (1.2, 1.1-1.5), neutrophil count (1.6, 1.1-2.3), and sP-selectin levels (1.9, 1.3-2.7) were associated with risk of ATE in patients with cancer; d-dimer was not associated with the risk of ATE (1.1, 0.9-1.4). After adjustment for age, sex, and smoking status the association prevailed for the neutrophil count (adjusted [adj.] SHR per doubling: 1.6, 1.1-2.4), and sP-selectin levels (1.8, 1.2-2.8). CONCLUSIONS: An elevated absolute neutrophil count and higher sP-selectin levels were associated with an increased risk of ATE in patients with cancer. Their role for predicting cancer-related ATE needs to be validated in further studies.

18.
Circulation ; 139(21): 2440-2450, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-30982349

RESUMO

BACKGROUND: NT-proBNP (N-terminal pro brain natriuretic peptide) levels are included in the multiparametric risk assessment approach for pulmonary arterial hypertension (PAH) outlined in PAH guidelines. However, data supporting the use of NT-proBNP risk thresholds in assessing prognosis in PAH are limited. The GRIPHON trial (Prostacyclin [PGI2] Receptor Agonist In Pulmonary Arterial Hypertension) provides an opportunity to assess the prognostic value of NT-proBNP thresholds in a controlled clinical trial and to evaluate the response to selexipag according to these thresholds. METHODS: The event-driven GRIPHON trial randomly assigned patients to selexipag or placebo. NT-proBNP was measured at regular intervals in GRIPHON. Here, patients were categorized post hoc into low, medium, and high NT-proBNP subgroups according to 2 independent sets of thresholds: (1) baseline tertiles: <271 ng/L; 271 to 1165 ng/L; >1165 ng/L; and (2) 2015 European Society of Cardiology/European Respiratory Society guidelines cutoffs: <300 ng/L; 300 to 1400 ng/L; >1400 ng/L. Hazard ratios (selexipag versus placebo) with 95% CIs were calculated for the primary end point (composite morbidity/mortality events) by NT-proBNP category at baseline using Cox proportional-hazards models, and at any time during the exposure period using a time-dependent Cox model. RESULTS: With both thresholds, baseline and follow-up NT-proBNP categories were highly prognostic for future morbidity/mortality events during the study ( P<0.0001). In the time-dependent analysis, the risk of experiencing a morbidity/mortality event was 92% and 83% lower in selexipag-treated patients with a low and medium NT-proBNP level, and 90% and 56% lower in placebo-treated patients with a low and medium NT-proBNP level, in comparison with patients with a high NT-proBNP level. Selexipag reduced the risk of morbidity/mortality events across all 3 NT-proBNP categories in both the baseline and time-dependent analyses, with a more pronounced treatment benefit of selexipag seen in the medium and low NT-proBNP subgroups (interaction P values 0.20 and 0.007 in the baseline and time-dependent analyses). CONCLUSIONS: These analyses further establish the prognostic relevance of NT-proBNP levels in PAH and provide first evidence for the association of NT-proBNP level and treatment response. Using 2 similar sets of thresholds, these analyses support the relevance of the low, medium, and high NT-proBNP categories as part of the multiparametric risk assessment approach outlined in the European Society of Cardiology/European Respiratory Society guidelines for the management of PAH patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01106014.

19.
Sci Rep ; 9(1): 5909, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30976042

RESUMO

The implantation of continuous - flow ventricular assist devices (VAD) is suggested to evoke angiodysplasia contributing to adverse events such as gastrointestinal bleeding. We evaluated in vivo capillary density and glycocalyx dimensions to investigate possible systemic microvascular changes in patients with chronic heart failure and VAD support vs. standard medical treatment. Forty-two patients with VAD support were compared to forty-one patients with ischemic and non-ischemic chronic heart failure (CHF) on standard pharmacotherapy and to a group of forty-two healthy subjects in a prospective cross-sectional study. Sublingual microcirculation was visualized using Sidestream Darkfield videomicroscopy and functional and perfused total capillary densities were quantified. Patients with VAD implantation were followed for one year and bleeding events were recorded. Median time after VAD implantation was 18 months. Patients were treated with centrifugal-flow devices (n = 31) or axial-flow devices (n = 11). Median functional capillary density was significantly lower in patients with VAD therapy as compared to CHF patients (196 vs. 255/mm2, p = 0.042, adjusted p-value). Functional and total capillary densities were 44% and 53% lower (both p < 0.001) in patients with VAD therapy when compared to healthy subjects. Cox regression analysis revealed loss of capillary density as a significant predictor of bleeding events during one -year follow-up of VAD patients (HR: 0.987, CI (95%): 0.977-0.998, p = 0.021 for functional and 0.992, CI (95%): 0.985-0.999, p = 0.03 for total capillary density). In conclusion, patients with VAD support exhibit capillary density rarefaction, which was associated with bleeding events. If confirmed independently, capillary impairment may be evaluated as novel marker of bleeding risk.

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