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1.
Biomarkers ; : 1-30, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32067501

RESUMO

Purpose To study temporal changes in metabolite profiles in post-acute coronary syndrome (ACS) patients, in particular prior to the development of recurrent ACS (reACS).Methods BIOMArCS is a prospective study including patients admitted for ACS, who underwent high-frequency blood sampling during 1 year follow-up. Within BIOMArCS, we performed a nested case-cohort analysis of 158 patients (28 cases of reACS). We determined 151 metabolites by nuclear magnetic resonance in 7 (median) blood samples per patient. Temporal evolution of the metabolites and their relation with reACS was assessed by joint modelling. Results are reported as adjusted (for clinical factors) hazard ratios (aHR).Results Median age was 64 (25th-75th percentile 56-72) years and 78% were men. After multiple testing correction (p < 0.001), high concentrations of extremely large VLDL particles (aHR 1.60/SD increase; 95%CI 1.25-2.08), very large VLDL particles (aHR 1.60/SD increase; 95%CI 1.25-2.08) and large VLDL particles (aHR 1.56/SD increase; 95%CI 1.22-2.05) were significantly associated with reACS. Moreover, these longitudinal particle concentrations showed a steady increase over time prior to reACS. Among the other metabolites, no significant associations were identified.Conclusion Post-ACS patients with persistent high concentrations of extremely large, very large and large VLDL particles have increased risk of reACS within 1 year.

2.
J Am Heart Assoc ; 9(4): e014457, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32063118

RESUMO

Background Sex differences in efficacy and safety of dual antiplatelet therapy remain uncertain because of the underrepresentation of women in cardiovascular trials. The aim of this study was to perform a sex-specific analysis of the pooled efficacy and safety data of clinical trials comparing a high potent P2Y12 inhibitor+aspirin with clopidogrel+aspirin in patients with acute coronary syndrome. Methods and Results A systematic literature search was performed. Randomized clinical trials that compared patients following percutaneous coronary intervention/acute coronary syndrome who were taking high potent P2Y12 inhibitors+aspirin versus clopidogrel+aspirin were selected. Random effects estimates were calculated and relative risks with 95% CIs on efficacy and safety end points were determined per sex. We included 6 randomized clinical trials comparing prasugrel/ticagrelor versus clopidogrel in 43 990 patients (13 030 women), with a median follow-up time of 1.06 years. Women and men had similar relative risk (RR) reduction for major cardiovascular events (women: RR, 0.89 [95% CI, 0.80-1.00; men: RR, 0.84 [95% CI, 0.79-0.91) (P for interaction=0.39). Regarding safety, women and men had similar risk of major bleeding by high-potency dual antiplatelet therapy (RR, 1.18 [95% CI, 0.98-1.41] versus RR, 1.03 [95% CI, 0.93-1.14]) (P for interaction=0.20). Conclusions The small and statistically insignificant difference in efficacy and safety estimates of high-potency dual antiplatelet therapy between women and men following percutaneous coronary intervention/acute coronary syndrome do not justify differential dual antiplatelet therapy treatment for both sexes.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31904342

RESUMO

OBJECTIVE: To examine the strength of the association between exercise capacity and health-related quality of life (HRQOL) during and after cardiac rehabilitation (CR) in patients with acute coronary syndrome (ACS) who completed CR. DESIGN: Prospective cohort study. SETTING: Outpatient CR center. PARTICIPANTS: Patients (N=607) with ACS who completed CR. INTERVENTIONS: Multidisciplinary 12-week exercise-based CR program. MAIN OUTCOME MEASURES: At baseline (pre-CR), the 6-Minute Walk Test (6MWT) was performed to determine exercise capacity, and the MacNew Heart Disease Health-related Quality of Life questionnaire was used to assess HRQOL. Measurements were repeated immediately after completion of CR (post-CR): at 12 months and 18 months follow-up. Multivariable linear regression, including an interaction term for time and exercise capacity, was applied to study the association between exercise capacity and HRQOL at different time points relative to CR, whereas model parameters were estimated by methods that accounted for dependency of repeated observations within individuals. RESULTS: Mean age in years ± SD was 58±8.9 and 82% of participants were male. Baseline mean 6MWT distance in meters ± SD was 563±77 and median (25th-75th percentile) global HRQOL was 5.5 (4.6-6.1) points. Mean 6MWT distance (P<.001) and the global (P<.001), physical (P<.001), emotional (P<.001) and social (P<.001) domains of HRQOL improved significantly during CR and continued to improve during follow-up post-CR. Independent of the timing relative to CR (ie, pre-CR, post-CR, or during follow-up), a difference of 10 m 6MWT distance was associated with a mean difference in the global HRQOL domain of 0.007 (95% confidence interval [CI], 0.001-0.014) points (P=.029) and a mean difference in the physical domain of 0.009 (95% CI, 0.001-0.017) points (P=.023). CONCLUSIONS: Better exercise capacity was significantly associated with higher scores on the global and physical domains of HRQOL, irrespective of the timing relative to CR, albeit these associations were weak. Hence, CR programs in secondary prevention should continue to aim at enhancing both HRQOL and exercise capacity.

4.
Clin Endocrinol (Oxf) ; 92(2): 150-158, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31638273

RESUMO

OBJECTIVES: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score. DESIGN: A cross-sectional study. PARTICIPANTS: 200 women aged >45 with PCOS, and 200 age-matched controls. MEASUREMENTS: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured. RESULTS: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P < .001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P < .001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. CONCLUSIONS: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning long-term risk for CVD.

5.
Int J Cardiol ; 299: 12-19, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31353156

RESUMO

BACKGROUND: Impaired renal function predicts mortality in acute coronary syndrome (ACS), but its evolution immediately following index ACS and preceding next ACS has not been described in detail. We aimed to describe this evolution using serial measurements of creatinine, glomerular filtration rate [eGFRCr] and cystatin C [CysC]. METHODS: From 844 ACS patients included in the BIOMArCS study, we analysed patient-specific longitudinal marker trajectories from the case-cohort of 187 patients to determine the risk of the endpoint (cardiovascular death or hospitalization for recurrent non-fatal ACS) during 1-year follow-up. Study included only patients with eGFRCr ≥ 30 ml/min/1.73 m2. Survival analyses were adjusted for GRACE risk score and based on data >30 days after the index ACS (mean of 8 sample per patient). RESULTS: Mean age was 63 years, 79% were men, 43% had STEMI, and 67% were in eGFR stages 2-3. During hospitalization for index ACS (median [IQR] duration: 5 (3-7) days), CysC levels indicated deterioration of renal function earlier than creatinine did (CysC peaked on day 3, versus day 6 for creatinine), and both stabilized after two weeks. Higher CysC levels, but not creatinine, predicted the endpoint independently of the GRACE score within the first year after index ACS (adjusted HR [95% CI] per 1SD increase: 1.68 [1.03-2.74]). CONCLUSION: Immediately following index ACS, plasma CysC levels deteriorate earlier than creatinine-based indices do, but neither marker stabilizes during hospitalization but on average two weeks after ACS. Serially measured CysC levels predict mortality or recurrence of ACS during 1-year follow-up independently of patients' GRACE risk score.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31872208

RESUMO

OBJECTIVES: Our goal was to report the long-term serial follow-up after transatrial-transpulmonary repair of tetralogy of Fallot (TOF) and to describe the influence of the timing of the repair on outcome. METHODS: We included all patients with TOF who had undergone transatrial-transpulmonary repair between 1970 and 2012. Records were reviewed for patient demographics, operative details and events during the follow-up period (death, pulmonary valve replacement, cardiac reinterventions and hospitalization/intervention for arrhythmias). In patients with elective early primary repair of TOF after 1990, a subanalysis of the optimal timing of TOF repair was performed. RESULTS: A total of 453 patients were included (63% male patients; 65% had transannular patch); 261 patients underwent primary elective repair after 1990. The median age at TOF repair was 0.7 years (25th-75th percentile 0.3-1.3) and decreased from 1.7 to 0.4 years from before 1990 to after 2000, respectively (P < 0.001). The median follow-up duration after TOF repair was 16.8 years (9.6-24.7). Events developed in 182 (40%) patients. In multivariable analysis, early repair of TOF (<6 months) [hazard ratio (HR) 3.06; P < 0.001] and complications after TOF repair (HR 2.18; P = 0.006) were found to be predictive for an event. In a subanalysis of the primary repair of TOF after 1990, the patients (n = 125) with elective early repair (<6 months) experienced significantly worse event-free survival compared to patients who had elective repair later (n = 136). In multivariable analysis, early repair (HR 3.00; P = 0.001) and postoperative complications (HR 2.12; P = 0.010) were associated with events in electively repaired patients with TOF. CONCLUSIONS: Transatrial-transpulmonary repair of TOF before the age of 6 months may be associated with more events during the long-term follow-up period.

7.
J Am Heart Assoc ; 8(23): e012993, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31771441

RESUMO

Background A genetic cause can be identified in 30% of noncompaction cardiomyopathy patients (NCCM) with clinical features ranging from asymptomatic cardiomyopathy to heart failure with major adverse cardiac events (MACE). Methods and Results To investigate genotype-phenotype correlations, the genotypes and clinical features of genetic NCCM patients were collected from the literature. We compared age at diagnosis, cardiac features and risk for MACE according to mode of inheritance and molecular effects for defects in the most common sarcomere genes and NCCM subtypes. Geno- and phenotypes of 561 NCCM patients from 172 studies showed increased risk in children for congenital heart defects (P<0.001) and MACE (P<0.001). In adult NCCM patients the main causes were single missense mutations in sarcomere genes. Children more frequently had an X-linked or mitochondrial inherited defect (P=0.001) or chromosomal anomalies (P<0.001). MYH7 was involved in 48% of the sarcomere gene mutations. MYH7 and ACTC1 mutations had lower risk for MACE than MYBPC3 and TTN (P=0.001). The NCCM/dilated cardiomyopathy cardiac phenotype was the most frequent subtype (56%; P=0.022) and was associated with an increased risk for MACE and high risk for left ventricular systolic dysfunction (<0.001). In multivariate binary logistic regression analysis MYBPC3, TTN, arrhythmia -, non-sarcomere non-arrhythmia cardiomyopathy-and X-linked genes were genetic predictors for MACE. Conclusions Sarcomere gene mutations were the most common cause in adult patients with lower risk of MACE. Children had multi-systemic disorders with severe outcome, suggesting that the diagnostic and clinical approaches should be adjusted to age at presentation. The observed genotype-phenotype correlations endorsed that DNA diagnostics for NCCM is important for clinical management and counseling of patients.

8.
Data Brief ; 27: 104750, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31763405

RESUMO

The Biomarker Study to Identify the Acute Risk of a Coronary Syndrome (BIOMArCS) is a prospective, observational study that has been designed to study the evolution of blood biomarkers in post-acute coronary syndrome (ACS) patients. In our recently published study "Temporal evolution of Myeloperoxidase and Galectin 3 during 1 year after acute coronary syndrome admission" [1] in the American Heart Journal, we demonstrated that repeatedly measuring MPO and Galectin-3 does not aid to differentiate between patients with and without adverse cardiac events during 1-year follow-up. In this Data-In-Brief article, we present further details on data collections and data analysis. In addition, a detailed description of baseline characteristics and the distribution of blood sampling moments is provided. The BIOMArCS dataset contains clinical information and follow-up data on all enrolled 844 patients. These patients underwent a median of 17 (25th -75th percentile 12-20) repeated blood samples in the first year after the index ACS. Blood samples were stored at -80 °C within a median of 82 (25th-75th percentile 58-117) minutes after withdrawal. We collected whole blood, citrate plasma, EDTA plasma, serum and DNA. The dataset used for the analysis in the accompanying research paper has been made available online. We welcome collaborations for further use of our data, whether or not in combination with other biobanks.

9.
Pediatr Cardiol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713652

RESUMO

A single 6-min walk test (6MWT) can be used to identify children with dilated cardiomyopathy (DCM) with a high risk of death or heart transplantation. To determine if repeated 6MWT has added value in addition to a single 6MWT in predicting death or heart transplantation in children with DCM. Prospective multicenter cohort study including ambulatory DCM patients ≥ 6 years. A 6MWT was performed 1 to 4 times per year. The distance walked was expressed as percentage of predicted (6MWD%). We compared the temporal evolution of 6MWD% in patients with and without the study endpoint (SE: all-cause death or heart transplantation), using a linear mixed effects model. In 57 patients, we obtained a median of 4 (IQR 2-6) 6MWTs per patient during a median of 3.0 years of observation (IQR 1.5-5.1). Fourteen patients reached a SE (3 deaths, 11 heart transplantations). At any time during follow-up, the average estimate of 6MWD% was significantly lower in patients with a SE compared to patients without a SE. In both patients groups, 6MWD% remained constant over time. An absolute 1% lower 6MWD% was associated with an 11% higher risk (hazard) of the SE (HR 0.90, 95% CI 0.86-0.95 p < 0.001). Children with DCM who died or underwent heart transplantation had systematically reduced 6MWD%. The performance of all patients was stable over time, so repeated measurement of 6MWT within this time frame had little added value over a single test.

10.
Thromb Haemost ; 119(12): 1947-1955, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31659734

RESUMO

OBJECTIVE: This article investigates whether longitudinally measured fibrinolysis factors are associated with cardiac events in patients with chronic heart failure (CHF). METHODS: A median of 9 (interquartile range [IQR] 5-10) serial, tri-monthly blood samples per patient were prospectively collected in 263 CHF patients during a median follow-up of 2.2 (IQR 1.4-2.5) years. Seventy patients (cases) reached the composite endpoint of cardiac death, heart failure hospitalization, left ventricular assist device, or heart transplantation. From all longitudinal samples, we selected baseline samples in all patients and the last two samples before the event in cases or the last sample available in event-free patients. Herein, we measured plasminogen activator inhibitor 1 (PAI-1), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and soluble urokinase plasminogen activator surface receptor (suPAR). Associations between temporal biomarker patterns during follow-up and the cardiac event were investigated using a joint model. RESULTS: Cases were on average older and showed higher New York Heart Association class than those who remained event-free. They also had lower blood pressures, and were more likely to have diabetes, renal failure, and atrial fibrillation. Longitudinally measured PAI-1, uPA, and suPAR were independently associated with adverse cardiac events after correction for clinical characteristics (hazard ratio [95% confidence interval]) per standard deviation increase of 2.09 (1.28-3.45) for PAI-1, 1.91 (1.18-3.24) for uPA, and 3.96 (2.48-6.63) for suPAR. Serial measurements of tPA were not significantly associated with the event after correction for multiple testing. CONCLUSION: Longitudinally measured PAI-1, uPA, and suPAR are strongly associated with adverse cardiac events during the course of CHF. If future research confirms our results, these fibrinolytic factors may carry potential for improved, and personalized, heart failure surveillance and treatment monitoring.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31596459

RESUMO

AIMS: To further elucidate the nature of the association between N-terminal pro-B type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-TnT), C-reactive protein (CRP), and clinical outcome, we examined the relationship between serial simultaneous measurements of echocardiographic parameters and these biomarkers in chronic heart failure (CHF) patients. METHODS AND RESULTS: In 117 CHF patients with ejection fraction ≤50%, NT-proBNP, hs-TnT, and CRP were measured simultaneously with echocardiographic evaluation at 6-month intervals until the end of 30 months follow-up or until an adverse clinical event occurred. Linear mixed effects models were used for data-analysis. Median follow-up was 2.2 years (interquartile range 1.5-2.6). We performed up to six follow-up evaluations with 55% of patients having at least three evaluations performed. A model containing all three biomarkers revealed that doubling of NT-proBNP was associated with a decrease in left ventricular ejection fraction by 1.83 (95% confidence interval -2.63 to -1.03)%, P < 0.0001; relative increase in mitral E/e' ratio by 12 (6-18)%, P < 0.0001; relative increase in mitral E/A ratio by 16 (9-23)%, P < 0.0001; decrease in tricuspid annular plane systolic excursion by 0.66 (-1.27 to -0.05) mm, P = 0.03; rise in tricuspid regurgitation peak systolic gradient by 2.74 (1.43-4.05) mmHg, P = 0.001; and increase in left ventricular and atrial dimensions, P < 0.05. Hs-TnT and CRP showed significant associations with some echocardiographic parameters after adjustment for clinical covariates, but after adjustment for the other biomarkers the associations were not significant. CONCLUSION: Serum NT-proBNP independently reflects changes in echocardiographic parameters of systolic function, left ventricular filling pressures, estimated pulmonary pressure, and chamber dimensions. Our results support further studies on NT-proBNP as a surrogate marker for haemodynamic congestion and herewith support its potential value for therapy guidance.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31596460

RESUMO

AIMS: The aim of this study was to evaluate the possible value of dobutamine stress cardiac magnetic resonance imaging (CMR) to predict adverse outcome in Tetralogy of Fallot (TOF) patients. METHODS AND RESULTS: In previous prospective multicentre studies, TOF patients underwent low-dose dobutamine stress CMR (7.5 µg/kg/min). Subsequently, during regular-care patient follow-up, patients were assessed for reaching the composite endpoint (cardiac death, arrhythmia-related hospitalization, or cardioversion/ablation, VO2 max ≤65% of predicted). A normal stress response was defined as a decrease in end-systolic volume (ESV) and increase in ejection fraction. The relative parameter change during stress was calculated as relative parameter change = [(parameterstress - parameterrest)/parameterrest] * 100. The predictive value of dobutamine stress CMR for the composite endpoint was determined using time-to-event analyses (Kaplan-Meier) and Cox proportional hazard analysis. We studied 100 patients [67 (67%) male, median age at baseline CMR 17.8 years (interquartile range 13.5-34.0), age at TOF repair 0.9 years (0.6-2.1)]. After a median follow-up of 8.6 years (6.7-14.1), 10 patients reached the composite endpoint. An abnormal stress response (30% vs. 4.4%, P = 0.021) was more frequently observed in composite endpoint patients. Also in endpoint patients, the relative decrease in right ventricular ESV decreased less during stress compared with the patients without an endpoint (-17 ± 15 vs. -26 ± 13 %, P = 0.045). Multivariable analyses identified an abnormal stress response (hazard ratio 10.4; 95% confidence interval 2.5-43.7; P = 0.001) as predictor for the composite endpoint. CONCLUSION: An abnormal ventricular response to dobutamine stress is associated with adverse outcome in patients with repaired TOF.

13.
Antioxidants (Basel) ; 8(10)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31618991

RESUMO

Antibodies to oxidized LDL (oxLDL) may be associated with improved outcomes in cardiovascular disease. However, analysis is restricted by heterogenous study design and endpoints. Our objective was to conduct a comprehensive systematic review assessing anti-oxLDL antibodies in relation to coronary artery disease (CAD). Through a systematic literature search, we identified all studies assessing the relationship of either, IgG or IgM ox-LDL/ copper-oxLDL/ malondialdehyde-LDL, with coronary atherosclerosis or cardiovascular events in populations with, and without, established CAD. Systematic review best practices were adhered to and study quality was assessed. An initial electronic database search identified 2059 records, which was subsequently followed by abstract and full-text review. Finally, we included 18 studies with over 1811 patients with CAD. The studies varied according to populations studied, conventional cardiovascular risk factors and interventional modalities used to assess CAD. IgM anti-oxLDL antibodies were found to indicate protection from more severe CAD and possibly cardiovascular events, whilst the relationship with IgG is more complex and difficult to elucidate, with studies reporting divergent results. In this systematic review, there is evidence that suggests a relationship between anti-oxLDL antibodies and CAD, especially for the IgM subclass. However, further studies, with well-characterized prospective cohorts, will be important to clarify these associations.

14.
J Clin Med ; 8(10)2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31547136

RESUMO

Soluble ST2 (sST2) is upregulated in response to myocardial stress and may serve as biomarker in adults with pulmonary hypertension (PH). This prospective cohort study investigated sST2 levels and its association with echocardiographic and hemodynamic measures, and adverse clinical outcomes in adults with PH of different etiologies. sST2 was measured during the diagnostic right heart catheterization for PH, in adult patients enrolled between May 2012 and October 2016. PH due to left heart failure was excluded. The association between sST2 and a primary endpoint composed of death or lung transplantation and a secondary composite endpoint including death, lung transplantation or heart failure, was investigated using Cox regression with adjustment for NT-proBNP. In total 104 patients were included (median age was 59 years, 66% woman, 51% pulmonary arterial hypertension). Median sST2 was 28 [IQR 20-46] ng/mL. Higher sST2 was associated with worse right ventricular dysfunction and higher mean pulmonary and right atrial pressures. Median follow-up was 3.3 [IQR 2.3-4.6] years. The primary and secondary endpoint occurred in 33 (31.7%) and 43 (41.3%) patients, respectively. sST2 was significantly associated with both endpoints (HR per 2-fold higher value 1.53, 95%CI 1.12-2.07, p = 0.007 and 1.45, 95%CI 1.10-1.90, p = 0.008, respectively). However, after adjustment for NT-proBNP, both associations did not reach statistical significance. In conclusions, higher sST2 levels are associated with more severe PH and right ventricular dysfunction and yields prognostic value in adults with PH, although not independently of NT-proBNP.

15.
Br J Anaesth ; 123(5): 565-569, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31547970

RESUMO

This case series presents 10 patients undergoing vascular surgery with asymptomatic elevated high-sensitivity troponin T concentrations, measured at outpatient clinic before surgery. Patients were included in the RAVE (Rotterdam Antiplatelet therapy in Vascular patiEnts) pilot study. All included patients underwent coronary angiography before surgery to identify significant obstructive coronary artery disease. We identified five out of 10 patients with high-grade stenosis and high-risk angiographic features of left main and/or proximal left anterior descending coronary artery disease. The study was terminated prematurely before any subject reached the study endpoint of 1 yr follow-up. This case series provides more insight into the meaning of preoperative troponin elevation and coronary angiographic features in vascular surgery patients. TRIAL REGISTRY NUMBER: NL5803.


Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Cuidados Pré-Operatórios/métodos , Troponina T/sangue , Procedimentos Cirúrgicos Vasculares , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/cirurgia , Método Duplo-Cego , Feminino , Humanos , Masculino , Projetos Piloto , Fatores de Risco
16.
Heart ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492701

RESUMO

OBJECTIVE: Despite its predictive value for mortality in various diseases, the relevance of growth differentiation factor-15 (GDF-15) as prognostic biomarker in pulmonary hypertension (PH) remains unclear. This study investigated the association between GDF-15 and outcomes in adults with PH. METHODS: This is a single-centre prospective observational cohort study. All adults with PH were included at the day of their diagnostic right heart catheterisation between 2012 and 2016. PH due to left heart disease was excluded. Venous blood sampling was performed and included GDF-15 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements. Kaplan-Meier curves and Cox regression analysis were used to investigate the association between GDF-15 and a composite endpoint of death or lung transplantation. We adjusted for age and NT-proBNP in multivariable analysis. Reference values were established by GDF-15 measurements in healthy controls. RESULTS: GDF-15 was measured in 103 patients (median age 59.2 years, 65% women, 51% pulmonary arterial hypertension). GDF-15 was elevated in 76 patients (74%). After a median follow-up of 3.4 (IQR 2.3-4.6) years, 32 patients (31.1%) reached the primary endpoint. Event-free survival 2 years after diagnosis was 100% in patients with normal GDF-15 versus 72.4% in patients with elevated GDF-15 (p=0.007). A significant association was found between GDF-15 and the primary endpoint (HR per twofold higher value 1.77, 95% CI 1.39 to 2.27, p<0.001), also after adjustment for age and NT-proBNP (HR 1.41, 95% CI 1.02 to 1.94, p=0.038). CONCLUSIONS: High GDF-15 levels are associated with an increased risk of death or transplant in adults with PH, independent of age and NT-proBNP. As non-specific biomarker, GDF-15 could particularly be useful to detect low-risk patients.

17.
J Am Heart Assoc ; 8(17): e013745, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31431113

RESUMO

Background Adults with a systemic right ventricle (sRV) have a high risk of cardiac complications. This study aimed to identify prognostic markers in adults with sRV based on clinical evaluation, echocardiography, and blood biomarkers. Methods and Results In this prospective cohort study, consecutive clinically stable adults with sRV caused by Mustard- or congenitally corrected transposition of the great arteries were included (2011-2013). Eighty-six patients were included (age 37±9 years, 65% male, 83% New York Heart Association functional class I, 76% Mustard transposition of the great arteries, 24% congenitally corrected transposition of the great arteries). Venous blood sampling was performed including N-terminal pro B-type natriuretic peptide, high-sensitive-troponin-T, high-sensitivity C-reactive protein, growth differentiation factor-15, galectin-3, red cell distribution width, estimated glomerular filtration rate, and hemoglobin. Besides conventional echocardiographic measurements, longitudinal, circumferential, and radial strain were assessed using strain analysis. During a median follow-up of 5.9 (interquartile range 5.3-6.3) years, 19 (22%) patients died or had heart failure (primary end point) and 29 (34%) patients died or had arrhythmia (secondary end point). Univariable Cox regression analysis was performed using dichotomous or standardized continuous variables. New York Heart Association functional class >I, systolic blood pressure, and most blood biomarkers were associated with the primary and secondary end point (galectin-3 not for primary, N-terminal pro B-type natriuretic peptide and high-sensitivity C-reactive protein not for secondary end point). Growth differentiation factor-15 showed the strongest association with both end points (hazard ratios; 2.44 [95% CI 1.67-3.57, P<0.001], 2.00 [95% CI 1.46-2.73, P<0.001], respectively). End-diastolic basal dimension of the subpulmonary ventricle was associated with both end points (hazard ratio: 1.95 [95% CI 1.34-2.85], P<0.001, 1.70 [95% CI 1.21-2.38, P=0.002], respectively). Concerning strain analysis, only sRV septal strain was associated with the secondary end point (hazard ratio 0.58 [95% CI 0.39-0.86], P=0.006). Conclusions Clinical, conventional echocardiographic, and blood measurements are important markers for risk stratification in adults with a sRV. The value of novel echocardiographic strain analysis seems limited.

18.
Invest Ophthalmol Vis Sci ; 60(10): 3595-3605, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31425584

RESUMO

Purpose: Uveal melanoma (UM) is characterized by multiple chromosomal rearrangements and recurrent mutated genes. The aim of this study was to investigate if copy number variations (CNV) alone and in combination with other genetic and clinico-histopathological variables can be used to stratify for disease-free survival (DFS) in enucleated patients with UM. Methods: We analyzed single nucleotide polymorphisms (SNP) array data of primary tumors and other clinical variables of 214 UM patients from the Rotterdam Ocular Melanoma Study (ROMS) cohort. Nonweighted hierarchical clustering of SNP array data was used to identify molecular subclasses with distinct CNV patterns. The subclasses associate with mutational status of BAP1, SF3B1, or EIF1AX. Cox proportional hazard models were then used to study the predictive performance of SNP array cluster-, mutation-, and clinico-histopathological data, and their combination for study endpoint risk. Results: Five clusters with distinct CNV patterns and concomitant mutations in BAP1, SF3B1, or EIF1AX were identified. The sample's cluster allocation contributed significantly to mutational status of samples in predicting the incidence of metastasis during a median of 45.6 (interquartile range [IQR]: 24.7-81.8) months of follow-up (P < 0.05) and vice versa. Furthermore, incorporating all data sources in one model yielded a 0.797 C-score during 100 months of follow-up. Conclusions: UM has distinct CNV patterns that correspond to different mutated driver genes. Incorporating clinico-histopathological, cluster and mutation data in the analysis results in good performance for UM-related DFS prediction.


Assuntos
Fator de Iniciação 1 em Eucariotos/genética , Enucleação Ocular , Melanoma/genética , Melanoma/cirurgia , Fosfoproteínas/genética , Polimorfismo de Nucleotídeo Único , Fatores de Processamento de RNA/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Neoplasias Uveais/genética , Neoplasias Uveais/cirurgia , Idoso , Variações do Número de Cópias de DNA , DNA de Neoplasias/genética , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias Uveais/diagnóstico
19.
Crit Care Med ; 47(11): 1564-1571, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31393321

RESUMO

OBJECTIVES: Prolonged emergency department to ICU waiting time may delay intensive care treatment, which could negatively affect patient outcomes. The aim of this study was to investigate whether emergency department to ICU time is associated with hospital mortality. DESIGN, SETTING, AND PATIENTS: We conducted a retrospective observational cohort study using data from the Dutch quality registry National Intensive Care Evaluation. Adult patients admitted to the ICU directly from the emergency department in six university hospitals, between 2009 and 2016, were included. Using a logistic regression model, we investigated the crude and adjusted (for disease severity; Acute Physiology and Chronic Health Evaluation IV probability) odds ratios of emergency department to ICU time on mortality. In addition, we assessed whether the Acute Physiology and Chronic Health Evaluation IV probability modified the effect of emergency department to ICU time on mortality. Secondary outcomes were ICU, 30-day, and 90-day mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 14,788 patients were included. The median emergency department to ICU time was 2.0 hours (interquartile range, 1.3-3.3 hr). Emergency department to ICU time was correlated to adjusted hospital mortality (p < 0.002), in particular in patients with the highest Acute Physiology and Chronic Health Evaluation IV probability and long emergency department to ICU time quintiles: odds ratio, 1.29; 95% CI, 1.02-1.64 (2.4-3.7 hr) and odds ratio, 1.54; 95% CI, 1.11-2.14 (> 3.7 hr), both compared with the reference category (< 1.2 hr). For 30-day and 90-day mortality, we found similar results. However, emergency department to ICU time was not correlated to adjusted ICU mortality (p = 0.20). CONCLUSIONS: Prolonged emergency department to ICU time (> 2.4 hr) is associated with increased hospital mortality after ICU admission, mainly driven by patients who had a higher Acute Physiology and Chronic Health Evaluation IV probability. We hereby provide evidence that rapid admission of the most critically ill patients to the ICU might reduce hospital mortality.

20.
Heart ; 105(19): 1479-1486, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31253696

RESUMO

BACKGROUND: Despite the promise of telemedicine to improve care for ischaemic heart disease, there are significant obstacles to implementation. Demonstrating improvement in patient-centred outcomes is important to support development of these innovative strategies. OBJECTIVE: To assess the impact of telemedicine interventions on mortality after acute myocardial infarction (AMI). METHODS: Articles were searched in MEDLINE, Cochrane Central Register of Controlled Trials, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Base de Dados de Enfermagem (BDENF), Indice Bibliográfico Español en Ciencias de la Salud (IBECs), Web of Science, Scopus and Google Scholar, from January 2004 to January 2018. Study selection and data extraction were performed by two independent reviewers. In-hospital mortality (primary outcome), and door-to-balloon (DTB) time, 30-day mortality and long-term mortality (secondary outcomes) were assessed. Random effects models were applied to estimate pooled results. RESULTS: Thirty non-randomised controlled and seven quasi-experimental studies were included (16 960 patients). They were classified as moderate or serious risk of bias by ROBINS-I (Risk Of Bias In Non-randomized Studies-of Interventions tool). In 31 studies, the intervention was prehospital ECG transmission. Telemedicine was associated with reduced in-hospital mortality compared with usual care (relative risk (RR) 0.63(95% confidence interval[CI] 0.55 to 0.72); I2 <0.001%). DTB time was consistently reduced (mean difference -28 (95% CI -35 to -20) min), but showed large heterogeneity (I2=94%). Thirty-day mortality (RR 0.62;95% CI 0.43 to 0.85) and long-term mortality (RR 0.61(95% CI 0.40 to 0.92)) were also reduced, with moderate heterogeneity (I2=52%). CONCLUSIONS: There is moderate-quality evidence that telemedicine strategies, in particular ECG transmission, combined with the usual care for AMI are associated with reduced in-hospital mortality and very-low quality evidence that they reduce DTB time, 30-day mortality and long-term mortality.

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