Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 101
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
1.
Biophys J ; 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31427066

RESUMO

Aortic valve replacement (AVR) does not usually restore physiological flow profiles. Complex flow profiles are associated with aorta dilatation, ventricle remodeling, aneurysms, and development of atherosclerosis. All these affect long-term morbidity and often require reoperations. In this pilot study, we aim to investigate an ability to optimize the real surgical AVR procedure toward flow profile associated with healthy persons. Four cases of surgical AVR (two with biological and two with mechanical valve prosthesis) with available post-treatment cardiac magnetic resonance imaging (MRI), including four-dimensional flow MRI and showing abnormal complex post-treatment hemodynamics, were investigated. All cases feature complex hemodynamic outcomes associated with valve-jet eccentricity and strong secondary flow characterized by helical flow and recirculation regions. A commercial computational fluid dynamics solver was used to simulate peak systolic hemodynamics of the real post-treatment outcome using patient-specific MRI measured boundary conditions. Then, an attempt to optimize hemodynamic outcome by modifying valve size and orientation as well as ascending aorta size reduction was made. Pressure drop, wall shear stress, secondary flow degree, helicity, maximal velocity, and turbulent kinetic energy were evaluated to characterize the AVR hemodynamic outcome. The proposed optimization strategy was successful in three of four cases investigated. Although no single parameter was identified as the sole predictor for a successful flow optimization, downsizing of the ascending aorta in combination with the valve orientation was the most effective optimization approach. Simulations promise to become an effective tool to predict hemodynamic outcome. The translation of these tools requires, however, studies with a larger cohort of patients followed by a prospective clinical validation study.

2.
Cell ; 178(1): 242-260.e29, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31155234

RESUMO

Gene expression in human tissue has primarily been studied on the transcriptional level, largely neglecting translational regulation. Here, we analyze the translatomes of 80 human hearts to identify new translation events and quantify the effect of translational regulation. We show extensive translational control of cardiac gene expression, which is orchestrated in a process-specific manner. Translation downstream of predicted disease-causing protein-truncating variants appears to be frequent, suggesting inefficient translation termination. We identify hundreds of previously undetected microproteins, expressed from lncRNAs and circRNAs, for which we validate the protein products in vivo. The translation of microproteins is not restricted to the heart and prominent in the translatomes of human kidney and liver. We associate these microproteins with diverse cellular processes and compartments and find that many locate to the mitochondria. Importantly, dozens of microproteins are translated from lncRNAs with well-characterized noncoding functions, indicating previously unrecognized biology.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31131388

RESUMO

OBJECTIVES: Complex blood flow profiles in the aorta are known to contribute to vessel dilatation. We studied flow profiles in the aorta in patients with aortic valve disease before and after surgical aortic valve replacement (AVR). METHODS: Thirty-four patients with aortic valve disease underwent 4-dimensional velocity-encoded magnetic resonance imaging before and after AVR (biological valve = 27, mechanical valve = 7). Seven healthy volunteers served as controls. Eccentricity (ES) and complex flow scores (CFS) were determined from the degree of helicity, vorticity and eccentricity of flow profiles in the aorta. Model-based therapy planning was used in 4 cases to improve in silico postoperative flow profiles by personalized adjustment of size, rotation and angulation of the valve as well as aorta diameter. RESULTS: Patients with aortic valve disease showed more complex flow than controls [median ES 2.5 (interquartile range (IQR) 2.3-2.7) vs 1.0 (IQR 1.0-1.0), P < 0.001, median CFS 4.7 (IQR 4.3-4.8) vs 1.0 (IQR 1.0-2.0), P < 0.001]. After surgery, flow complexity in the total patient cohort was reduced, but remained significantly higher compared to controls [median ES 2.3 (IQR 1.9-2.3) vs 1.0 (IQR 1.0-1.0), P < 0.001, median CFS 3.8 (IQR 3.0-4.3) vs 1.0 (IQR 1.0-2.0), P < 0.001]. In patients after mechanical AVR, flow complexity fell substantially and showed no difference from controls [median ES 1.0 (IQR 1.0-2.3) vs 1.0 (IQR 1.0-1.0), P = 0.46, median CFS 1.0 (IQR 1.0-3.3) vs 1.0 (IQR 1.0-2.0), P = 0.71]. In all 4 selected cases (biological, n = 2; mechanical, n = 2), model-based therapy planning reduced in silico complexity of flow profiles compared to the existing post-surgical findings [median ES 1.7 (IQR 1.4-1.7) vs 2.3 (IQR 2.3-2.3); CFS 1.7 (IQR 1.4-2.5) vs 3.8 (IQR 3.3-4.3)]. CONCLUSIONS: Abnormal flow profiles in the aorta more frequently persist after surgical AVR. Model-based therapy planning might have the potential to optimize treatment for best possible individual outcome. CLINICAL TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT03172338, 1 June 2017, retrospectively registered; NCT02591940, 30 October 2015, retrospectively registered.

5.
Eur Heart J ; 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31145798

RESUMO

AIMS: The antiplatelet treatment strategy providing optimal balance between thrombotic and bleeding risks in patients undergoing coronary artery bypass grafting (CABG) is unclear. We prospectively compared the efficacy of ticagrelor and aspirin after CABG. METHODS AND RESULTS: We randomly assigned in double-blind fashion patients scheduled for CABG to either ticagrelor 90 mg twice daily or 100 mg aspirin (1:1) once daily. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), repeat revascularization, and stroke 12 months after CABG. The main safety endpoint was based on the Bleeding Academic Research Consortium classification, defined as BARC ≥4 for periprocedural and hospital stay-related bleedings and BARC ≥3 for post-discharge bleedings. The study was prematurely halted after recruitment of 1859 out of 3850 planned patients. Twelve months after CABG, the primary endpoint occurred in 86 out of 931 patients (9.7%) in the ticagrelor group and in 73 out of 928 patients (8.2%) in the aspirin group [hazard ratio 1.19; 95% confidence interval (CI) 0.87-1.62; P = 0.28]. All-cause mortality (ticagrelor 2.5% vs. aspirin 2.6%, hazard ratio 0.96, CI 0.53-1.72; P = 0.89), cardiovascular death (ticagrelor 1.2% vs. aspirin 1.4%, hazard ratio 0.85, CI 0.38-1.89; P = 0.68), MI (ticagrelor 2.1% vs. aspirin 3.4%, hazard ratio 0.63, CI 0.36-1.12, P = 0.12), and stroke (ticagrelor 3.1% vs. 2.6%, hazard ratio 1.21, CI 0.70-2.08; P = 0.49), showed no significant difference between the ticagrelor and aspirin group. The main safety endpoint was also not significantly different (ticagrelor 3.7% vs. aspirin 3.2%, hazard ratio 1.17, CI 0.71-1.92; P = 0.53). CONCLUSION: In this prematurely terminated and thus underpowered randomized trial of ticagrelor vs. aspirin in patients after CABG no significant differences in major cardiovascular events or major bleeding could be demonstrated. CLINICALTRIALS.GOV IDENTIFIER: NCT01755520.

7.
J Mol Cell Cardiol ; 131: 53-65, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31005484

RESUMO

AIMS: Atrial contractile dysfunction is associated with increased mortality in heart failure (HF). We have shown previously that a metabolic syndrome-based model of HFpEF and a model of hypertensive heart disease (HHD) have impaired left atrial (LA) function in vivo (rat). In this study we postulate, that left atrial cardiomyocyte (CM) and cardiac fibroblast (CF) paracrine interaction related to the inositol 1,4,5-trisphosphate signalling cascade is pivotal for the manifestation of atrial mechanical dysfunction in HF and that quantitative atrial remodeling is highly disease-dependent. METHODS AND RESULTS: Differential remodeling was observed in HHD and HFpEF as indicated by an increase of atrial size in vivo (HFpEF), unchanged fibrosis (HHD and HFpEF) and a decrease of CM size (HHD). Baseline contractile performance of rat CM in vitro was enhanced in HFpEF. Upon treatment with conditioned medium from their respective stretched CF (CM-SF), CM (at 21 weeks) of WT showed increased Ca2+ transient (CaT) amplitudes related to the paracrine activity of the inotrope endothelin (ET-1) and inositol 1,4,5-trisphosphate induced Ca2+ release. Concentration of ET-1 was increased in CM-SF and atrial tissue from WT as compared to HHD and HFpEF. In HHD, CM-SF had no relevant effect on CaT kinetics. However, in HFpEF, CM-SF increased diastolic Ca2+ and slowed Ca2+ removal, potentially contributing to an in-vivo decompensation. During disease progression (i.e. at 27 weeks), HFpEF displayed dysfunctional excitation-contraction-coupling (ECC) due to lower sarcoplasmic-reticulum Ca2+ content unrelated to CF-CM interaction or ET-1, but associated with enhanced nuclear [Ca2+]. In human patients, tissue ET-1 was not related to the presence of arterial hypertension or obesity. CONCLUSIONS: Atrial remodeling is a complex entity that is highly disease and stage dependent. The activity of fibrosis related to paracrine interaction (e.g. ET-1) might contribute to in vitro and in vivo atrial dysfunction. However, during later stages of disease, ECC is impaired unrelated to CF.

8.
Am J Transplant ; 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30884079

RESUMO

In the 12-month, open-label MANDELA study, patients were randomized at month 6 after heart transplantation to (i) convert to calcineurin inhibitor (CNI)-free immunosuppression with everolimus (EVR), mycophenolic acid and steroids (CNI-free, n=71), or to (ii) continue reduced-exposure CNI, with EVR and steroids (EVR/redCNI, n=74). Tacrolimus was administered in 48.8% of EVR/redCNI patients and 52.6% of CNI-free patients at radomization. Both strategies improved and stabilized renal function based on the primary endpoint (estimated GFR at month 18 post-transplant post-randomization) with superiority of the CNI-free group versus EVR/redCNI : mean 64.1mL/min/1.73m2 versus 52.9mL/min/1.73m2 ; difference +11.3mL/min/1.73m2 (p<0.001). By month 18, estimated GFR had increased by ≥10mL/min/1.732 in 31.8% and 55.2% of EVR/redCNI and CNI-free patients, respectively, and by ≥25 mL/min/1.73m2 in 4.5% and 20.9%. Rates of biopsy-proven acute rejection (BPAR) were 6.8% and 21.1%; all cases were without hemodynamic compromise. BPAR was less frequent with EVR/redCNI versus the CNI-free regimen (p=0.015); 6/15 episodes in CNI-free patients occurred with EVR concentration <5ng/mL. Rates of adverse events and associated discontinuations were comparable EVR/redCNI from month 6 achieved stable renal function with infrequent BPAR. One-year renal function can be improved by early conversion to EVR-based CNI-free therapy but requires close EVR monitoring. This article is protected by copyright. All rights reserved.

9.
Cell ; 176(6): 1340-1355.e15, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30799037

RESUMO

Th17 cells provide protection at barrier tissues but may also contribute to immune pathology. The relevance and induction mechanisms of pathologic Th17 responses in humans are poorly understood. Here, we identify the mucocutaneous pathobiont Candida albicans as the major direct inducer of human anti-fungal Th17 cells. Th17 cells directed against other fungi are induced by cross-reactivity to C. albicans. Intestinal inflammation expands total C. albicans and cross-reactive Th17 cells. Strikingly, Th17 cells cross-reactive to the airborne fungus Aspergillus fumigatus are selectively activated and expanded in patients with airway inflammation, especially during acute allergic bronchopulmonary aspergillosis. This indicates a direct link between protective intestinal Th17 responses against C. albicans and lung inflammation caused by airborne fungi. We identify heterologous immunity to a single, ubiquitous member of the microbiota as a central mechanism for systemic induction of human anti-fungal Th17 responses and as a potential risk factor for pulmonary inflammatory diseases.

10.
Am J Transplant ; 19(6): 1759-1769, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30615259

RESUMO

Calcineurin inhibitor (CNI) therapy after lung transplantation increases risk of kidney failure. Early everolimus-based quadruple low CNI immunosuppression may improve renal function without compromising efficacy or safety. A prospective, randomized, open-label, 12-month multicenter trial was conducted at 8 German sites. Patients 3-18 months after lung transplantation were randomized (1:1), stratified by baseline estimated glomerular filtration rate (eGFR). In the quadruple low CNI regimen, patients received everolimus (target trough level 3-5 ng/mL) with reduced CNI (tacrolimus 3-5 ng/mL or cyclosporine 25-75 ng/mL) and a cell cycle inhibitor plus prednisone. In the standard triple CNI regimen, patients received tacrolimus (target trough level >5 ng/mL) or cyclosporine (>100 ng/mL) and a cell cycle inhibitor plus prednisone. Of the 180 patients screened, 130 were randomized: 67 in the quadruple low CNI group and 63 in the standard triple CNI group. The primary endpoint (eGFR after 12 months) demonstrated superiority of the quadruple low CNI regimen: 64.5 mL/min vs 54.6 mL/min for the standard triple group (least squares mean, analysis of covariance; P < .001). Key efficacy parameters (biopsy-proven acute rejection, chronic lung allograft dysfunction, and death) and safety endpoints were similar between both groups. Quadruple low CNI immunosuppression early after lung transplantation was demonstrated to be efficacious and safe. Clinical trials registry: ClinicalTrials.gov NCT01404325.

12.
Nature ; 564(7736): 352-353, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30560955
13.
Transpl Int ; 31(11): 1223-1232, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29885002

RESUMO

Internationally 3% of the donor hearts are distributed to re-transplant patients. In Eurotransplant, only patients with a primary graft dysfunction (PGD) within 1 week after heart transplantation (HTX) are indicated for high urgency listing. The aim of this study is to provide evidence for the discussion on whether these patients should still be allocated with priority. All consecutive HTX performed in the period 1981-2015 were included. Multivariate Cox' model was built including: donor and recipient age and gender, ischaemia time, recipient diagnose, urgency status and era. The study population included 18 490 HTX, of these 463 (2.6%) were repeat transplants. The major indications for re-HTX were cardiac allograft vasculopathy (CAV) (50%), PGD (26%) and acute rejection (21%). In a multivariate model, compared with first HTX hazards ratio and 95% confidence interval for repeat HTX were 2.27 (1.83-2.82) for PGD, 2.24 (1.76-2.85) for acute rejection and 1.22 (1.00-1.48) for CAV (P < 0.0001). Outcome after cardiac re-HTX strongly depends on the indication for re-HTX with acceptable outcomes for CAV. In contrast, just 47.5% of all hearts transplanted in patients who were re-transplanted for PGD still functioned at 1-month post-transplant. Alternative options like VA-ECMO should be first offered before opting for acute re-transplantation.

14.
Lancet Respir Med ; 6(5): 357-367, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29650408

RESUMO

BACKGROUND: Severe primary graft dysfunction (PGD) of grade 3 (PGD3) is a common serious complication following lung transplantation. We aimed to assess physiological donor lung preservation using the Organ Care System (OCS) Lung device compared with cold static storage. METHODS: In this non-inferiority, randomised, controlled, open-label, phase 3 trial (INSPIRE) recipients were aged 18 years or older and were registered as standard criteria primary double lung transplant candidates. Eligible donors were younger than 65 years old with a ratio of partial pressure of oxygen in arterial blood to the fraction of inspired oxygen of more than 300 mm Hg. Transplant recipients were randomly assigned (1:1) with permuted blocks, stratified by centre, to receive standard criteria donor lungs preserved in the OCS Lung device (OCS arm) or cold storage at 4°C (control arm). The composite primary effectiveness endpoint was absence of PGD3 within the first 72 h after transplant and 30-day survival in the per-protocol population, with a stringent 4% non-inferiority margin. Superiority was tested upon meeting non-inferiority. The primary safety endpoint was the mean number of lung graft-related serious adverse events within 30 days of transplant. We did analyses in the per-protocol and intention-to-treat populations. This trial is registered with ClinicalTrials.gov, number NCT01630434. FINDINGS: Between Nov 17, 2011, and Nov 24, 2014, we randomly assigned 370 patients, and 320 (86%) underwent transplantation (n=151 OCS and n=169 control); follow-up was completed in Nov 24, 2016. The primary endpoint was met in 112 (79·4%) of 141 patients (95% CI 71·8 to 85·8) in the OCS group compared with 116 (70·3%) of 165 patients (62·7 to 77·2) in the control group (non-inferiority point estimate -9·1%; 95% CI -∞ to -1·0; p=0·0038; and superiority test p=0·068). Patient survival at day 30 post-transplant was 135 (95·7%) of 141 patients (95% CI 91·0-98·4) in the OCS group and 165 patients (100%; 97·8-100·0) in the control group (p=0·0090) and at 12 months was 126 (89·4%) of 141 patients (83·1-93·9) for the OCS group compared with 146 (88·1%) of 165 patients (81·8-92·8) for the control group. Incidence of PGD3 within 72 h was reported in 25 (17·7%) of 141 patients in the OCS group (95% CI 11·8 to 25·1) and 49 (29·7%) of 165 patients in the control group (22·8 to 37·3; superiority test p=0·015). The primary safety endpoint was met (0·23 lung graft-related serious adverse events in the OCS group compared with 0·28 events in the control group [point estimate -0·045%; 95% CI -∞ to 0·047; non-inferiority test p=0·020]). In the intention-to-treat population, causes of death at 30 days and in hospital were lung graft failure or lung infection (n=2 for OCS vs n=7 for control), cardiac causes (n=4 vs n=1), vascular or stroke (n=3 vs n=0), metabolic coma (n=0 vs n=2), and generalised sepsis (n=0 vs n=1). INTERPRETATION: The INSPIRE trial met its primary effectiveness and safety endpoints. Although no short-term survival benefit was reported, further research is needed to see whether the reduced incidence of PGD3 within 72 h of a transplant might translate into earlier recovery and improved long-term outcomes after lung transplantation. FUNDING: TransMedics Inc.


Assuntos
Transplante de Pulmão/métodos , Preservação de Órgãos/instrumentação , Disfunção Primária do Enxerto/prevenção & controle , Adulto , Criopreservação/métodos , Feminino , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Soluções para Preservação de Órgãos , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
15.
Dtsch Arztebl Int ; 115(8): 124-130, 2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-29526184

RESUMO

BACKGROUND: Chronic heart failure (CHF) is the most common reason for hospital admissions in Germany. For the National Disease Management Guideline (NDMG) on CHF, a multidisciplinary expert panel revised the chapters on drug therapy, invasive therapy, and care coordination, following the methods of evidence-based medicine. METHODS: Recommendations are based on international guideline adaptations or systematic literature search. They were developed by a multidisciplinary expert panel, approved in a formal consensus procedure, and tested in open consultation, as specified by the requirements for S3 guidelines. RESULTS: The pharmacological treatment is based on ACE inhibitors, beta-blockers and mineralocorticoid receptor antagonists as well as diuretics to treat fluid retention, if present. Sacubitril/Valsartan and ivabradine showed positive effects on mortality in large but methodologically limited RCT. They are recommended if established combination therapy is not sufficient for symptom control, or if drugs are not tolerated/contraindicated. The indications for pacemakers or defibrillators have been confined to patient subgroups in which clinical trials have shown a clear benefit. Moreover, the goals of treatment and the patient's expectations should be aligned with each other. Structured care programs, specialized nurses, remote, or telephone monitoring showed moderate effects on patient related outcomes in RCT. CONCLUSION: All patients with heart failure are suggested to be enrolled in a structured program (e.g., a disease management program) including coordinated multidisciplinary care and continuous educational interventions. In patients with a poor prognosis, more intensive care is recommended, e.g. specialized nurses, or telephone support.

16.
Cardiovasc Res ; 114(2): 312-323, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29036612

RESUMO

Aims: CD40 ligand (CD40L) signaling controls vascular oxidative stress and related dysfunction in angiotensin-II-induced arterial hypertension by regulating vascular immune cell recruitment and platelet activation. Here we investigated the role of CD40L in experimental hyperlipidemia. Methods and results: Male wild type and CD40L-/- mice (C57BL/6 background) were subjected to high fat diet for sixteen weeks. Weight, cholesterol, HDL, and LDL levels, endothelial function (isometric tension recording), oxidative stress (NADPH oxidase expression, dihydroethidium fluorescence) and inflammatory parameters (inducible nitric oxide synthase, interleukin-6 expression) were assessed. CD40L expression, weight, leptin and lipids were increased, and endothelial dysfunction, oxidative stress and inflammation were more pronounced in wild type mice on a high fat diet, all of which was almost normalized by CD40L deficiency. Similar results were obtained in diabetic db/db mice with CD40/TRAF6 inhibitor (6877002) therapy. In a small human study higher serum sCD40L levels and an inflammatory phenotype were detected in the blood and Aorta ascendens of obese patients (body mass index > 35) that underwent by-pass surgery. Conclusion: CD40L controls obesity-associated vascular inflammation, oxidative stress and endothelial dysfunction in mice and potentially humans. Thus, CD40L represents a therapeutic target in lipid metabolic disorders which is a leading cause in cardiovascular disease.

17.
Heart Surg Forum ; 21(6): E527-E533, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30604679

RESUMO

Background Several risk models target the issue of posttransplant survival, but none of them have been validated in a large European cohort. This aspect is important, in a time of the planned change of the Eurotransplant allocation system to a scoring system. Material and Methods Data of 761 heart transplant recipients from the Eurotransplant region with a total follow up of 5027 patient-years were analyzed. We assessed 30-day to 10-year freedom from graft failure. Existing post-transplant mortality risk models, IMPACT, Meld-XI and Columbia Risk Stratification Score were (RSS) were evaluated. A new risk model was created and the predictive accuracy was compared with the existing risk scores, with a focus on LVAD patients. Results Thirty-day, 1-year, 5-year and 10-year rates of freedom from graft failure were 78.3±1.5%, 68.8±1.71%, 59.1±1.8% and 44.1±1.9. The 1-year incidence of graft failure varied from 14.1% to 50% (RSS), from 22.9% to 57.1 (IMPACT) and from 24.9% to 42.6% using MELD-XI. Our newly adjusted risk score showed an improved area under the curve (AUC) of 0.69 (95% CI 0.64-0.72) with better discrimination in the intermediate to moderate risk cohort (CABDES Score). Conclusion IMPACT, Meld-XI and RSS were suitable to predict posttransplant graft failure only in a high and low risk cohort. CABDES Score, might be an alternative scoring system, with donor age and eGFR beeing the strongest predictors. Implementation of the IMPACT score within the new Eurotransplant Cardiac Allocation Score for patient prioritization for heart transplantation, should be reevaluated.


Assuntos
Transplante de Coração/mortalidade , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Europa (Continente)/epidemiologia , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
18.
Am Heart J ; 179: 69-76, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27595681

RESUMO

BACKGROUND: For patients with coronary artery disease undergoing coronary bypass surgery, acetylsalicylic acid (ASA) currently represents the gold standard of antiplatelet treatment. However, adverse cardiovascular event rates in the first year after coronary artery bypass grafting (CABG) still exceed 10%. Graft failure, which is predominantly mediated by platelet aggregation, has been identified as a major contributing factor in this context. Therefore, intensified platelet inhibition is likely to be beneficial. Ticagrelor, an oral, reversibly binding and direct-acting P2Y12 receptor antagonist, provides a rapid, competent, and consistent platelet inhibition and has shown beneficial results compared with clopidogrel in the subset of patients undergoing bypass surgery in a large previous trial. HYPOTHESIS: Ticagrelor is superior to ASA for the prevention of major cardiovascular events within 1 year after CABG. STUDY DESIGN: The TiCAB trial (NCT01755520) is a multicenter, phase III, double-blind, double-dummy, randomized trial comparing ticagrelor with ASA for the prevention of major cardiovascular events within 12 months after CABG. Patients undergoing CABG will be randomized in a 1:1 fashion to either ticagrelor 90 mg twice daily or ASA 100 mg once daily. The study medication will be started within 24 hours after surgery and maintained for 12 months. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization at 12 months after CABG. The sample size is based on an expected event rate of 13% of the primary end point within the first 12 months after randomization in the control group, a 2-sided α level of .0492 (to preserve the overall significance level of .05 after planned interim analysis), a power of 0.80%, 2-sided testing, and an expected relative risk of 0.775 in the active group compared with the control group and a dropout rate of 2%. According to power calculations based on a superiority design for ticagrelor, it is estimated that 3,850 patients should be enrolled. SUMMARY: There is clinical equipoise on the issue of optimal platelet inhibition after CABG. The TiCAB trial will provide a pivotal comparison of the efficacy and safety of ticagrelor compared with ASA after CABG.


Assuntos
Adenosina/análogos & derivados , Aspirina/uso terapêutico , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/terapia , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Adenosina/uso terapêutico , Idoso , Doenças Cardiovasculares/mortalidade , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Revascularização Miocárdica/estatística & dados numéricos , Acidente Vascular Cerebral/epidemiologia , Ticagrelor , Resultado do Tratamento
19.
Interact Cardiovasc Thorac Surg ; 23(3): 383-90, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27222112

RESUMO

OBJECTIVES: Involvement of the mitral valve (MV) apparatus represents a challenge in surgical ventricular repair (SVR) of posterior left ventricular (LV) aneurysms. This study sought to investigate whether multislice computed tomography (MSCT) assessment can be used to optimize the surgical procedure for posterior LV aneurysms. METHODS: Thirty patients (m : w = 24 : 6, age 38-78, median 66 years; mean New York Heart Association class 2.98) with posterior LV aneurysm were operated upon. MSCT was performed in 24 patients before and after surgery. End-diastolic and end-systolic volumes of LV and aneurysm were indexed to body surface area (LVEDVI/LVESVI, AEDVI/AESVI). The MV apparatus was characterized by coaptation distance (CD), tenting area (TA), MV closure angle (MVCA), MV annulus area (MVAA) and interpapillary muscle distance (IMD). RESULTS: Thirty-day mortality was 10% and 5-year survival rate was 83%. After surgery, LVEDVI decreased from 151.2 ± 84.1 to 85.7 ± 28.3 ml/m(2) (P = 0.001) and LVESVI from 110.6 ± 88.8 to 50.2 ± 22.9 ml/m(2) (P = 0.001). LV ejection fraction increased from 31.5 ± 15.1 to 43.4 ± 9.9% (P = 0.001). Preoperative MSCT showed significantly higher values of MVAA, CD and TA in patients who needed MV repair or replacement. Postoperative reduction of mitral regurgitation in patients without MV surgery corresponded with significant reduction in intercommissural diameter, anteroposterior diameter, MVAA, TA, CD, MVCA and IMD. CONCLUSIONS: MSCT represents an excellent diagnostic tool for the assessment of MV and LV geometry. MSCT-guided SVR of submitral LV aneurysms leads to excellent mid-term results. On the basis of the MSCT assessment, we propose an algorithm for surgical planning in posterior LV aneurysms.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Aneurisma Cardíaco/diagnóstico por imagem , Aneurisma Cardíaco/cirurgia , Valva Mitral/fisiopatologia , Tomografia Computadorizada Multidetectores , Remodelação Ventricular/fisiologia , Idoso , Feminino , Aneurisma Cardíaco/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Taxa de Sobrevida , Função Ventricular Esquerda
20.
Eur J Cardiothorac Surg ; 50(4): 713-720, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26935407

RESUMO

OBJECTIVES: Aortic valve replacement (AVR) via minimally invasive surgery (MIS) may provide clinical benefits in patients with aortic valve disease. A new class of bioprosthetic valves that enable rapid deployment AVR (RDAVR) may facilitate MIS. We here report the 1-year results of a randomized, multicentre trial comparing the outcomes for MIS-RDAVR with those for conventional AVR via full sternotomy (FS) with a commercially available stented aortic bioprosthesis. METHODS: A total of 100 patients with aortic stenosis were enrolled in a prospective, multicentre, randomized comparison trial (CADENCE-MIS). Key exclusion criteria included AVR requiring concomitant procedures, ejection fraction of <25% and recent myocardial infarction or stroke. Patients were randomized to undergo MIS-RDAVR via upper hemisternotomy (EDWARDS INTUITY) or AVR via FS with a commercially available stented valve. Procedural, early and late clinical outcomes were assessed for both groups. Haemodynamic performance was evaluated by an echocardiography CoreLaboratory. RESULTS: Technical success was achieved in 94% of MIS-RDAVR patients. MIS-RDAVR was associated with significantly reduced cross-clamp times compared with FS (41.3 ± 20.3 vs 54.0 ± 20.3 min, P < 0.001). Clinical and functional outcomes were similar at 30 days and 1 year postoperatively for both groups. While both groups received a similarly sized implanted valve (22.9 ± 2.1 mm MIS-RDAVR vs 23.0 ± 2.1 mm FS-AVR; P = 0.91), MIS-RDAVR patients had significantly lower peak gradients 1 year postoperatively (16.9 ± 5.3 vs 21.9 ± 8.6 mmHg; P = 0.033) and a trend towards lower mean gradients (9.1 ± 2.9 vs 11.5 ± 4.3 mmHg; P = 0.082). In addition, MIS-RDAVR patients had a significantly larger effective orifice area 1 year postoperatively (1.9 ± 0.5 vs 1.7 ± 0.4 cm2; P = 0.047). Paravalvular leaks, however, were significantly more common in the MIS-RDAVR group (P = 0.027). CONCLUSIONS: MIS-RDAVR is associated with a significantly reduced cross-clamp time and better valvular haemodynamic function than FS-AVR. However, paravalvular leak rates are higher with MIS-RDAVR.


Assuntos
Estenose da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Procedimentos Cirúrgicos Minimamente Invasivos , Idoso , Bioprótese , Feminino , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/instrumentação , Implante de Prótese de Valva Cardíaca/métodos , Hemodinâmica , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Prospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA