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1.
Eur Heart J ; 40(3): 283-291, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30371767

RESUMO

Aims: Patients with acute coronary syndrome who present initially with ST-elevation on the electrocardiogram but, subsequently, show complete normalization of the ST-segment and relief of symptoms before reperfusion therapy are referred to as transient ST-segment elevation myocardial infarction (STEMI) and pose a therapeutic challenge. It is unclear what the optimal timing of revascularization is for these patients and whether they should be treated with a STEMI-like or a non-ST-segment elevation myocardial infarction (NSTEMI)-like invasive approach. The aim of the study is to determine the effect of an immediate vs. a delayed invasive strategy on infarct size measured by cardiac magnetic resonance imaging (CMR). Methods and results: In a randomized clinical trial, 142 patients with transient STEMI with symptoms of any duration were randomized to an immediate (STEMI-like) [0.3 h; interquartile range (IQR) 0.2-0.7 h] or a delayed (NSTEMI-like) invasive strategy (22.7 h; IQR 18.2-27.3 h). Infarct size as percentage of the left ventricular myocardial mass measured by CMR at day four was generally small and not different between the immediate and the delayed invasive group (1.3%; IQR 0.0-3.5% vs. 1.5% IQR 0.0-4.1%, P = 0.48). By intention to treat, there was no difference in major adverse cardiac events (MACE), defined as death, reinfarction, or target vessel revascularization at 30 days (2.9% vs. 2.8%, P = 1.00). However, four additional patients (5.6%) in the delayed invasive strategy required urgent intervention due to signs and symptoms of reinfarction while awaiting angiography. Conclusion: Overall, infarct size in transient STEMI is small and is not influenced by an immediate or delayed invasive strategy. In addition, short-term MACE was low and not different between the treatment groups.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Eletrocardiografia , Humanos
2.
Am J Hum Genet ; 91(5): 823-38, 2012 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-23063622

RESUMO

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.


Assuntos
Estudo de Associação Genômica Ampla , Lipídeos/genética , Locos de Características Quantitativas , HDL-Colesterol/sangue , HDL-Colesterol/genética , LDL-Colesterol/sangue , LDL-Colesterol/genética , Feminino , Genótipo , Humanos , Lipídeos/sangue , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , Triglicerídeos/sangue , Triglicerídeos/genética , População Branca
3.
J Mol Cell Cardiol ; 67: 94-102, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24389343

RESUMO

Acute myocardial infarction (AMI) is accompanied by increased expression of Toll like receptors (TLR)-2 and TLR4 on circulating monocytes. In animal models, blocking TLR2/4 signaling reduces inflammatory cell influx and infarct size. The clinical consequences of TLR activation during AMI in humans are unknown, including its role in long-term cardiac functional outcome Therefore, we analyzed gene expression in whole blood samples from 28 patients with an acute ST elevation myocardial infarction (STEMI), enrolled in the EXenatide trial for AMI patients (EXAMI), both at admission and after 4-month follow-up, by whole genome expression profiling and real-time PCR. Cardiac function was determined by cardiac magnetic resonance (CMR) imaging at baseline and after 4-month follow-up. TLR pathway activation was shown by increased expression of TLR4 and its downstream genes, including IL-18R1, IL-18R2, IL-8, MMP9, HIF1A, and NFKBIA. In contrast, expression of the classical TLR-induced genes, TNF, was reduced. Bioinformatics analysis and in vitro experiments explained this noncanonical TLR response by identification of a pivotal role for HIF-1α. The extent of TLR activation and IL-18R1/2 expression in circulating cells preceded massive troponin-T release and correlated with the CMR-measured ischemic area (R=0.48, p=0.01). In conclusion, we identified a novel HIF-1-dependent noncanonical TLR activation pathway in circulating leukocytes leading to enhanced IL-18R expression which correlated with the magnitude of the ischemic area. This knowledge may contribute to our mechanistic understanding of the involvement of the innate immune system during STEMI and may yield diagnostic and prognostic value for patients with myocardial infarction.


Assuntos
Interleucina-18/metabolismo , Infarto do Miocárdio/fisiopatologia , Receptor 4 Toll-Like/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Interleucina-18/sangue , Interleucina-18/genética , Leucócitos/metabolismo , Pessoa de Meia-Idade , Receptor 4 Toll-Like/sangue , Receptor 4 Toll-Like/genética , Regulação para Cima
4.
Crit Care ; 17(1): R31, 2013 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-23425514

RESUMO

INTRODUCTION: Mild therapeutic hypothermia (MTH) is a worldwide used therapy to improve neurological outcome in patients successfully resuscitated after cardiac arrest (CA). Preclinical data suggest that timing and speed of induction are related to reduction of secondary brain damage and improved outcome. METHODS: Aiming at a rapid induction and stable maintenance phase, MTH induced via continuous peritoneal lavage (PL) using the Velomedix Inc. automated PL system was evaluated and compared to historical controls in which hypothermia was achieved using cooled saline intravenous infusions and cooled blankets. RESULTS: In 16 PL patients, time to reach the core target temperature of 32.5°C was 30 minutes (interquartile range (IQR): 19 to 60), which was significantly faster compare to 150 minutes (IQR: 112 to 240) in controls. The median rate of cooling during the induction phase in the PL group of 4.1°C/h (IQR: 2.2 to 8.2) was significantly faster compared to 0.9°C/h (IQR: 0.5 to 1.3) in controls. During the 24-hour maintenance phase mean core temperature in the PL patients was 32.38 ± 0.18°C (range: 32.03 to 32.69°C) and in control patients 32.46 ± 0.48°C (range: 31.20 to 33.63°C), indicating more steady temperature control in the PL group compared to controls. Furthermore, the coefficient of variation (VC) for temperature during the maintenance phase was lower in the PL group (VC: 0.5%) compared to the control group (VC: 1.5%). In contrast to 23% of the control patients, none of the PL patients showed an overshoot of hypothermia below 31°C during the maintenance phase. Survival and neurological outcome was not different between the two groups. Neither shivering nor complications related to insertion or use of the PL method were observed. CONCLUSIONS: Using PL in post-CA patients results in a rapidly reached target temperature and a very precise maintenance, unprecedented in clinical studies evaluating MTH techniques. This opens the way to investigate the effects on neurological outcome and survival of ultra-rapid cooling compared to standard cooling in controlled trials in various patient groups. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01016236


Assuntos
Parada Cardíaca/terapia , Hipotermia Induzida/métodos , Segurança do Paciente , Lavagem Peritoneal/métodos , Ressuscitação/métodos , Idoso , Feminino , Parada Cardíaca/diagnóstico , Humanos , Hipotermia Induzida/normas , Masculino , Pessoa de Meia-Idade , Segurança do Paciente/normas , Lavagem Peritoneal/normas , Estudos Prospectivos , Ressuscitação/normas , Fatores de Tempo , Resultado do Tratamento
5.
Eur J Nucl Med Mol Imaging ; 39(1): 102-12, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22005845

RESUMO

BACKGROUND: There has been increasing interest in quantitative myocardial blood flow (MBF) imaging over the last years and it is expected to become a routinely used technique in clinical practice. Positron emission tomography (PET) using [(15)O]H(2)O is the established gold standard for quantification of MBF in vivo. A fundamental issue when performing quantitative MBF imaging is to define the limits of MBF in a clinically suitable population. The aims of the present study were to determine the limits of MBF and to determine the relationship among coronary artery disease (CAD) risk factors, gender and MBF in a predominantly symptomatic patient cohort without significant CAD. METHODS: A total of 128 patients (mean age 54 ± 10 years, 50 men) with a low to intermediate pretest likelihood of CAD were referred for noninvasive evaluation of CAD using a hybrid PET/computed tomography (PET/CT) scanner. MBF was quantified with [(15)O]H(2)O at rest and during adenosine-induced hyperaemia. Obstructive CAD was excluded in these patients by means of invasive or CT-based coronary angiography. RESULTS: Global average baseline MBF values were 0.91 ± 0.34 and 1.09 ± 0.30 ml·min(-1)·g(-1) (range 0.54-2.35 and 0.59-2.75 ml·min(-1)·g(-1)) in men and women, respectively (p < 0.01). However, no gender-dependent difference in baseline MBF was seen following correction for rate-pressure product (0.98 ± 0.45 and 1.09 ± 0.30 ml·min(-1)·g(-1) in men and women, respectively; p = 0.08). Global average hyperaemic MBF values were 3.44 ± 1.20 ml·min(-1)·g(-1) in the whole study population, and 2.90 ± 0.85 and 3.78 ± 1.27 ml·min(-1)·g(-1) (range 1.52-5.22 and 1.72-8.15 ml·min(-1)·g(-1)) in men and women, respectively (p < 0.001). Multivariate analysis identified male gender, age and body mass index as having an independently negative impact on hyperaemic MBF. CONCLUSION: Gender, age and body mass index substantially influence reference values and should be corrected for when interpreting hyperaemic MBF values.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Água , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Reserva Fracionada de Fluxo Miocárdico , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Radioisótopos de Oxigênio , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
6.
J Nucl Cardiol ; 19(2): 256-64, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22076826

RESUMO

BACKGROUND: The incremental value of CAC over traditional risk factors to predict coronary vasodilator dysfunction and inherent myocardial blood flow (MBF) impairment is only scarcely documented (MBF). The aim of this study was therefore to evaluate the relationship between CAC content, hyperemic MBF, and coronary flow reserve (CFR) in patients undergoing hybrid (15)O-water PET/CT imaging. METHODS: We evaluated 173 (mean age 56 ± 10, 78 men) patients with a low to intermediate likelihood for coronary artery disease (CAD), without a documented history of CAD, undergoing vasodilator stress (15)O-water PET/CT and CAC scoring. Obstructive coronary artery disease was excluded by means of invasive (n = 44) or CT-based coronary angiography (n = 129). RESULTS: 91 of 173 patients (52%) had a CAC score of zero. Of those with CAC, the CAC score was 0.1-99.9, 100-399.9, and ≥400 in 31%, 12%, and 5% of patients, respectively. Global CAC score showed significant inverse correlation with hyperemic MBF (r = -0.32, P < .001). With increasing CAC score, there was a decline in hyperemic MBF on a per-patient basis [3.70, 3.30, 2.68, and 2.53 mL · min(-1) · g(-1), with total CAC score of 0, 0.1-99.9, 100-399.9, and ≥400, respectively (P < .001)]. CFR showed a stepwise decline with increasing levels of CAC (3.70, 3.32, 2.94, and 2.93, P < .05). Multivariate analysis, including age, BMI, and CAD risk factors, revealed that only age, male gender, BMI, and hypercholesterolemia were associated with reduced stress perfusion. Furthermore, only diabetes and age were independently associated with CFR. CONCLUSION: In patients without significant obstructive CAD, a greater CAC burden is associated with a decreased hyperemic MBF and CFR. However, this association disappeared after adjustment for traditional CAD risk factors. These results suggest that CAC does not add incremental value regarding hyperemic MBF and CFR over established CAD risk factors in patients without obstructive CAD.


Assuntos
Calcinose/diagnóstico , Calcinose/epidemiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Hiperemia/diagnóstico , Imagem de Perfusão do Miocárdio/estatística & dados numéricos , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Feminino , Humanos , Hiperemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Radioisótopos de Oxigênio , Prevalência , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Técnica de Subtração , Água
7.
Eur Heart J ; 32(11): 1362-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21406440

RESUMO

A recent report of the EuroHeart project has shown that women are still underrepresented in many cardiovascular clinical trials, while important gender differences are present within most areas of heart disease. As the burden of cardiovascular disease is increasing in middle-aged women relative to men, a more profound understanding is needed of the fundamental biological differences that exist between men and women. In the current review, we aim to address the need for more explanatory sex-specific cardiovascular research to be able to adapt existing guidelines for a better heart health in women.


Assuntos
Doenças Cardiovasculares/etiologia , Síndrome Coronariana Aguda/etiologia , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/mortalidade , Europa (Continente)/epidemiologia , Feminino , Promoção da Saúde , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Isquemia Miocárdica/etiologia , Fatores de Risco , Fatores Sexuais , Estresse Psicológico/complicações , Acidente Vascular Cerebral/etiologia
8.
Cells ; 9(2)2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085575

RESUMO

: Introduction: Preeclampsia (PE) represents a hypertensive pregnancy disorder that is associated with increased cardiovascular disease (CVD) risk. This increased risk has been attributed to accelerated atherosclerosis, with inflammation being a major contributor. Neutrophils play an important role in the onset and progression of atherosclerosis and have been associated with vascular damage in the placenta as well as the chronic inflammatory state in women with PE. We therefore investigated whether circulating neutrophil numbers or reactivity were associated with the presence and severity of subclinical atherosclerosis in women with a history of PE. METHODS: Women aged 45-60 years with a 10 to 20 years earlier history of early onset preeclampsia (delivery <34 weeks of gestation) (n = 90), but without symptomatic CVD burden were screened for the presence of subclinical coronary artery disease (CAD) using both contrast-enhanced and non-contrast coronary CT angiography. Subclinical CAD was defined as a coronary artery calcium (CAC) score ≥100 Agatston Units and/or ≥50% coronary luminal stenosis. We assessed whether the numbers and activity of circulating neutrophils were associated with the presence of subclinical CAD and as secondary outcome measurements, with the presence of any calcium (CAC score > 0 AU) or stenosis, categorized as absent (0%), minimal to mild (>0 and <50%), and moderate to severe (≥50%) narrowing of the coronary artery. Blood was drawn just before CT and neutrophil numbers were assessed by flow cytometry. In addition, the presence of the chemokine receptors CXCR2 and CXCR4, which are known to be instrumental in neutrophil recruitment, and neutrophil activity upon stimulation with the bacterial peptide N-Formylmethionyl-leucyl-phenylalanine (fMLF) was assessed by flow cytometry. RESULTS: Of the participating women, with an average age of 49 years, 13% (12 out of 90) presented with subclinical signs of CAD (CAC score ≥100 AU and/or ≥50% luminal stenosis), and 37% (33 out of 90) had a positive CAC score (>0). Total white blood cell count and neutrophil counts were not associated with the presence of subclinical CAD or with a positive CAC score. When assessing the presence of the chemokine receptors CXCR4 and CXCR2, we observed a slight decrease of neutrophil CXCR2 expression in women with CAC (median MFI 22.0 [interquartile range (IQR) 20.2-23.8]) compared to women without CAC (23.8 [IQR 21.6-25.6], p = 0.02). We observed no differences regarding neutrophil CXCR4 expression. In addition, expression of the early activity marker CD35 was slightly lower on neutrophils of women with subclinical CAD (median MFI 1.6 [IQR 1.5-1.9] compared to 1.9 [IQR 1.7-2.1] in women without CAD, p = 0.02). However, for all findings, statistical significance disappeared after adjustment for multiple testing. CONCLUSION: Our findings indicate that neutrophil counts and (re)activity are not directly associated with silent CAD disease burden and as such are not suitable as biomarkers to predict the presence of subclinical CAD in a high-risk population of women with a history of preeclampsia.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Neutrófilos/metabolismo , Pré-Eclâmpsia/sangue , Estudos de Coortes , Angiografia Coronária , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade , Gravidez , Prognóstico , Fatores de Risco , Calcificação Vascular/diagnóstico por imagem
10.
Open Heart ; 2(1): e000231, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26339493

RESUMO

BACKGROUND: Health-related quality of life (HRQOL) reflects the general well-being of individuals. In patients with coronary artery disease (CAD), HRQOL is compromised. Female patients with CAD have been reported to have lower HRQOL. In this study, we investigate gender differences in HRQOL and in associations of patient characteristics with HRQOL in patients with coronary angiography (CAG). METHODS: We cross-sectionally analysed patients from the Utrecht Coronary Biobank undergoing CAG. All patients filled in an HRQOL questionnaire (RAND-36 and EuroQoL) on inclusion. RAND-36 and EuroQoL HRQOL measures were compared between the genders across indications for CAG, CAD severity and treatment of CAD. RAND-36 HRQOL measures were compared with the general Dutch population. Additionally, we assessed interactions of gender with patient characteristics in their association with HRQOL (EuroQoL). RESULTS: We included 1421 patients (1020 men and 401 women) with a mean age of 65 in our analysis. Women reported lower HRQOL measures than men (mean EuroQoL self-rated health grade 6.84±1.49 in men, 6.46±1.40 in women, p<0.001). The reduction in RAND-36 HRQOL as compared with the general Dutch population was larger in women than in men. From regression analysis, we found that diabetes, a history of cardiovascular disease and symptoms of shortness of breath determined HRQOL (EuroQoL) more strongly in men than in women. CONCLUSIONS: Women reported lower HRQOL than men throughout all indications for CAG and regardless of CAD severity or treatment. As compared with the general population, the reduction in HRQOL was more extreme in women than in men. Evident gender differences were found in determinants of HRQOL in patients undergoing CAG, which deserve attention in future research. TRIAL REGISTRATION: NCT02304744 (clinicaltrials.gov).

11.
Circ Cardiovasc Interv ; 8(3): e001786, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25717044

RESUMO

BACKGROUND: A total of 40% to 50% of patients with ST-segment-elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET). METHODS AND RESULTS: Sixty patients with ST-segment-elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure-flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure-velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H2 (15)O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low signal intensity within a gadolinium-enhanced area. Myocardial perfusion was quantified using H2 (15)O PET. Reference HMR values were obtained in 16 stable patients undergoing coronary angiography. Complete data sets were available in 48 patients of which 24 developed MVI. Adequate pressure-velocity loops were obtained in 29 patients. HMR in the culprit artery in patients with MVI was significantly higher than in patients without MVI (MVI, 3.33±1.50 mm Hg/cm per second versus no MVI, 2.41±1.26 mm Hg/cm per second; P=0.03). MVI was associated with higher pressure at zero flow (45.68±13.16 versus 32.01±14.98 mm Hg; P=0.015). Multivariable analysis showed HMR to independently predict MVI (P=0.04). The optimal cutoff value for HMR was 2.5 mm Hg/cm per second. High HMR was associated with decreased myocardial blood flow on PET (myocardial perfusion reserve <2.0, 3.18±1.42 mm Hg/cm per second versus myocardial perfusion reserve ≥2.0, 2.24±1.19 mm Hg/cm per second; P=0.04). CONCLUSIONS: Doppler-flow-derived physiological indices of coronary resistance (HMR) and extravascular compression (pressure at zero flow) obtained immediately after successful primary PCI predict MVI and decreased PET myocardial blood flow. CLINICAL TRIAL REGISTRATION URL: http://www.trialregister.nl. Unique identifier: NTR3164.


Assuntos
Circulação Coronária/fisiologia , Vasos Coronários/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Idoso , Velocidade do Fluxo Sanguíneo , Vasos Coronários/diagnóstico por imagem , Ecocardiografia Doppler , Feminino , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Resistência Vascular/fisiologia
13.
Eur J Prev Cardiol ; 21(11): 1443-50, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23804558

RESUMO

BACKGROUND: Cardiovascular diseases remain the leading cause of death in women and there is a need for more accurate risk assessment scores. The aims of our study were to compare the accuracy of several widely used cardiac risk assessment scores in predicting the likelihood of obstructive coronary artery disease (CAD) on CT coronary angiography (CTCA) in symptomatic women and to explore which female-specific risk factors were independent predictors of obstructive CAD on CTCA and whether adding these risk factors to pre-test probability scores would improve their predictive value. METHODS AND RESULTS: Data were obtained from a cohort of 228 consecutively included symptomatic women undergoing evaluation for CAD and referred for CTCA. Obstructive CAD was defined as ≥50% luminal stenosis on CTCA. Pre-test probability for CAD was calculated according to the Diamond and Forrester score, New score, Duke clinical score, and an updated Diamond and Forrester score. Female-specific factors were obtained by a written questionnaire. Pre-test probability scores were compared with ROC analysis and showed that only the New score and the updated Diamond and Forrester score were significant predictive scores for obstructive CAD on CTCA (area under the curve, AUC, 0.67, p < 0.01; AUC 0.61, p = 0.04, respectively). Multivariable logistic regression analysis identified that gestational diabetes mellitus (GDM) and oestrogen status were independent predictors of obstructive CAD when adjusted for the pre-test probability scores. The updated Diamond and Forrester score was used for net reclassification improvement (NRI) analysis, since the New score already accounts for oestrogen status. Adding GDM and oestrogen status to the updated Diamond and Forrester score resulted in a significant NRI (p = 0.04). CONCLUSIONS: There is a large variability in prediction of obstructive CAD using different pre-test probability risk scores in symptomatic women. Logistic regression analysis revealed that oestrogen status and GDM were independently associated with the occurrence of obstructive stenosis on CTCA. The predictive ability of cardiac pre-test probability scores improved significantly with the addition of oestrogen status and GDM.


Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/etiologia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/etiologia , Vasos Coronários/diagnóstico por imagem , Técnicas de Apoio para a Decisão , Tomografia Computadorizada Multidetectores , Idoso , Doença da Artéria Coronariana/sangue , Estenose Coronária/sangue , Estudos Transversais , Diabetes Gestacional/diagnóstico , Estrogênios/sangue , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Gravidez , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Inquéritos e Questionários
14.
Eur J Heart Fail ; 15(12): 1429-37, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23883653

RESUMO

Aim Increasing evidence suggests an important role for hyperactivation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal LVEF (HFNEF) and hypertension. Moreover, the level of renal sympathetic activation is directly related to the severity of heart failure. Since percutaneous renal denervation (pRDN) has been shown to be effective in modulating elevated SNS activity in patients with hypertension, it can be hypothesized that pRDN has a positive effect on HFNEF. The DIASTOLE trial will investigate whether renal sympathetic denervation influences parameters of HFNEF. Methods DIASTOLE is a multicentre, randomized controlled trial. Sixty patients, diagnosed with HFNEF and treated for hypertension, will be randomly allocated in a 1:1 ratio to undergo renal denervation on top of medical treatment (n = 30) or to maintain medical treatment alone (n = 30). The primary objective is to investigate the efficacy of pRDN by means of pulsed wave Doppler echocardiographic parameters. Secondary objectives include safety of pRDN and a comparison of changes in the following parameters after pRDN: LV mass, LV volume, LVEF, and left atrial volume as determined by magnetic resonance imaging. Also, MIBG (metaiodobenzylguanidine) uptake and washout, BNP levels, blood pressure, heart rate variability, exercise capacity, and quality of life will be assessed. Perspective DIASTOLE is a randomized controlled trial evaluating renal denervation as a treatment option for HFNEF. The results of the current trial will provide important information regarding the treatment of HFNEF, and therefore may have major impact on future therapeutic strategies. Trail registration NCT01583881.


Assuntos
Insuficiência Cardíaca , Rim/inervação , Simpatectomia/métodos , Sistema Nervoso Simpático/cirurgia , Ecocardiografia Doppler de Pulso/métodos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Volume Sistólico , Resultado do Tratamento
15.
J Nucl Med ; 54(1): 55-63, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23232274

RESUMO

UNLABELLED: Hybrid imaging using PET in conjunction with CT-based coronary angiography (PET/CTCA) enables near-simultaneous quantification of myocardial blood flow (MBF) and anatomical evaluation of coronary arteries. CTCA is an excellent imaging modality to rule out obstructive coronary artery disease (CAD), but functional assessment is warranted in the presence of a CTCA-observed stenosis because the specificity of CTCA is relatively low. Quantitative H(2)(15)O PET/CTCA may yield complementary information and enhance diagnostic accuracy. The purpose of this study was to evaluate the diagnostic accuracy of quantitative H(2)(15)O PET/CTCA in a clinical cohort of patients with suspected CAD who underwent both cardiac H(2)(15)O PET/CTCA and invasive coronary angiography (ICA). In addition, this study aimed to evaluate and compare the accuracy of hyperemic MBF versus coronary flow reserve (CFR). METHODS: Patients (n = 120; mean age ± SD, 61 ± 10 y; 77 men and 43 women) with a predominantly intermediate pretest likelihood for CAD underwent both quantitative H(2)(15)O PET/CTCA and ICA. A ≥50% stenosis at ICA or a fractional flow reserve ≤ 0.80 was considered significant. RESULTS: Obstructive CAD was diagnosed in 49 of 120 patients (41%). The diagnostic accuracy of hyperemic MBF was significantly higher than CFR (80% vs. 68%, respectively, P = 0.02), with optimal cutoff values of 1.86 mL/min/g and 2.30, respectively. On a per-patient basis, the sensitivity, specificity, negative predictive value, and positive predictive value of CTCA were 100%, 34%, 100%, and 51%, respectively, as compared with 76%, 83%, 83%, and 76%, respectively, for quantitative hyperemic MBF PET. Quantitative H(2)(15)O PET/CTCA reduced the number of false-positive CTCA studies from 47 to 6, although 12 of 49 true-positive CTCAs were incorrectly reclassified as false-negative hybrid scans on the basis of (presumably) sufficient hyperemic MBF. Compared with CTCA (61%) or H(2)(15)O PET (80%) alone (both P < 0.05), the hybrid approach significantly improved diagnostic accuracy (85%). CONCLUSION: The diagnostic accuracy of quantitative H(2)(15)O PET/CTCA is superior to either H(2)(15)O PET or CTCA alone for the detection of clinically significant CAD. Hyperemic MBF was more accurate than CFR, implying that a single measurement of MBF in diagnostic protocols may suffice.


Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Água , Estudos de Coortes , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioisótopos de Oxigênio , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Sensibilidade e Especificidade
16.
World J Cardiol ; 4(2): 36-47, 2012 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-22379536

RESUMO

AIM: To investigate potential gender differences in the prevalence of cardiovascular risk factors, cardiovascular disease (CVD) management, and prognosis in acute coronary syndrome (ACS). METHODS: A systematic literature search was performed through Medline using pre-specified keywords. An additional search was performed, focusing specifically on randomized controlled clinical trials in relation to therapeutic intervention and prognosis. In total, 92 relevant articles were found. RESULTS: Women with CVD tended to have more hypertension and diabetes at the time of presentation, whereas men were more likely to smoke. Coronary angiography and revascularization by percutaneous coronary intervention were performed more often in men. Women were at a greater risk of short-term mortality and complications after revascularization. Interestingly, women under 40 years presenting with ACS were at highest risk of cardiovascular death compared with men of the same age, irrespective of risk factors. This disadvantage disappeared in older age. The long-term mortality risk of ACS was similar in men and women, and even in favor of women. CONCLUSION: Mortality rates are higher among young women with ACS, but this difference tends to disappear with age, and long-term prognosis is even better among older women.

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