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1.
J Mol Cell Cardiol ; 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32305360

RESUMO

BACKGROUND: Cardiac troponins are the preferred biomarkers of acute myocardial infarction. Despite superior sensitivity, serial testing of Troponins to identify patients suffering acute coronary syndromes is still required in many cases to overcome limited specificity. Moreover, unstable angina pectoris relies on reported symptoms in the troponin-negative group. In this study, we investigated genome-wide miRNA levels in a prospective cohort of patients with clinically suspected ACS and determined their diagnostic value by applying an in silico neural network. METHODS: PAXgene blood and serum samples were drawn and hsTnT was measured in patients at initial presentation to our Chest-Pain Unit. After clinical and diagnostic workup, patients were adjudicated by senior cardiologists in duty to their final diagnosis: STEMI, NSTEMI, unstable angina pectoris and non-ACS patients. ACS patients and a cohort of healthy controls underwent deep transcriptome sequencing. Machine learning was implemented to construct diagnostic miRNA classifiers. RESULTS: We developed a neural network model which incorporates 34 validated ACS miRNAs, showing excellent classification results. By further developing additional machine learning models and selecting the best miRNAs, we achieved an accuracy of 0.96 (95% CI 0.96-0.97), sensitivity of 0.95, specificity of 0.96 and AUC of 0.99. The one-point hsTnT value reached an accuracy of 0.89, sensitivity of 0.82, specificity of 0.96, and AUC of 0.96. CONCLUSIONS: Here we show the concept of neural network based biomarkers for ACS. This approach also opens the possibility to include multi-modal data points to further increase precision and perform classification of other ACS differential diagnoses.

2.
Eur Heart J Acute Cardiovasc Care ; : 2048872620907322, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186398

RESUMO

BACKGROUND: D-dimer is elevated in a variety of conditions. The purpose of this study was to assess the positive predictive value of D-dimer to rule in patients with confirmed pulmonary embolism, deep vein thrombosis, acute aortic dissection or thrombosis of the upper extremity in comparison to patients with elevated D-dimer for other reasons. METHODS AND RESULTS: We studied 1334 patients presenting to the emergency department with pulmonary embolism (n=193), deep vein thrombosis (n=73), acute aortic dissection (n=22), thrombosis of the upper extremity (n=8) and 1038 controls. The positive predictive value was increased with higher D-dimer concentrations improving the ability to identify diseases with high thrombus burden. Patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity showed a maximum positive predictive value of 85.2% at a D-dimer level of 7.8 mg/L (95% confidence interval (CI) 78.1 to 90.4). The maximum positive predictive value was lower in cancer patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity, reaching 68.9% at a D-dimer level of 7.5 mg/L (95% CI 57.4 to 78.4). The positive likelihood ratio was very consistent with the positive predictive value. Using a cut-off level of 0.5 mg/L, D-dimer showed a high sensitivity of at least 93%, but a very low specificity of nearly 0%. Conversely, an optimised cut-off value of 4.6 mg/L increased specificity to 95% for the detection of life-threatening venous thromboembolism, acute aortic dissection or thrombosis of the upper extremity at the costs of moderate sensitivities (58% for pulmonary embolism, 41% for deep vein thrombosis, 65% for pulmonary embolism with co-existent deep vein thrombosis, 50% for acute aortic dissection and 13% for thrombosis of the upper extremity). Using the same cut-off in cancer patients, higher values were observed for sensitivity at a specificity level of more than 95%. The area under the curve for the discrimination of venous thromboembolism/acute aortic dissection/thrombosis of the upper extremity from controls was significantly higher in cancer versus non-cancer patients (area under the curve 0.905 in cancer patients, 95% CI 0.89 to 0.92, vs. area under the curve 0.857 in non-cancer patients, 95% CI 0.84 to 0.88; P=0.0349). CONCLUSION: D-dimers are useful not only to rule out but also to rule in venous thromboembolism and acute aortic dissection with an at least moderate discriminatory ability, both in patients with and without cancer.

3.
Clin Biochem ; 67: 7-11, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30872042

RESUMO

OBJECTIVE: To evaluate the long term biological variation of high-sensitivity cardiac troponin T (hs-cTnT) in stable outpatients with cardiovascular disease (CVD). METHODS: After applying 8 exclusion criteria to 965 patients, hs-cTnT was measured at index visit and at a 12-month interval in 169 stable outpatients presenting for routine follow-up visits for any CVD. Stability was defined as absence of any endpoint within the follow-up period. Reference change values (RCVs) and minimal important differences (MIDs) were determined to assess biological variation of hs-cTnT. RESULTS: MID and RCV for the 12 months interval in patients were 3.8 ng/L or 44.2%, respectively. MID and transformed MID values were lower than the corresponding RCV with a value of 5.1 ng/L for the transformed RCV and 28.1% for the transformed MID. Similar patterns were shown in different subgroups as sex, age, and renal function. We observed a baseline hs-cTnT value dependent change of MID and RCV with increasing values for MID and decreasing values for RCV which converge to stable values between a baseline hs-cTNT value of 11 to 25 ng/L. CONCLUSIONS: Biological variation of hs-cTnT over 12 months in stable outpatients depends on the concentration at index visit, and is consistent among important prespecified subgroups. MID shows a low biovariability over 12 months. Clinical Trials Identifier:NCT01954303.


Assuntos
Doenças Cardiovasculares/sangue , Pacientes Ambulatoriais , Troponina T/sangue , Idoso , Idoso de 80 Anos ou mais , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Fatores de Tempo
4.
Sci Rep ; 9(1): 3866, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30846742

RESUMO

Recordings of aortic root movement represent one of the first accomplishments of ultrasound in medicine and mark the beginning of functional cardiac imaging. However, the underlying mechanism is not completely understood. Since the aortic root is directly connected to the cardiac skeleton we hypothesize, that the amplitude of systolic aortic root motion (SARM) may be mainly caused by displacement of the cardiac base towards the apex and might therefore be used as measure of left ventricular longitudinal function (LV-LF). One hundred and eighty patients with dilated cardiomyopathy and 180 healthy controls were prospectively included into this study. SARM was lower in patients compared to controls (9 ± 3 mm vs. 12 ± 2 mm, p < 0.001) and lowest in patients with cardiovascular events (9 ± 3 mm vs. 7 ± 3 mm, p < 0.001). During a median follow-up time of 38 months, the combined end-point of cardiovascular death or hospitalization for heart failure was reached by 25 patients (13.9%). Reduced SARM had significant prognostic impact on outcome (hazard ratio 0.74, 95% confidence interval 0.63-0.88, p < 0.001) and remained an independent predictor in the multivariate analysis. Compared to parameters with potential influence on its mechanism, SARM correlated best (r = 0.75, p < 0.001) with global longitudinal strain (GLS). SARM may therefore represent an alternative echocardiographic parameter for the assessment of LV-LF, particularly when GLS is not feasible or apical views are not available.

5.
J Am Soc Echocardiogr ; 31(6): 733-742, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29402506

RESUMO

BACKGROUND: Impaired left ventricular (LV) longitudinal function (LF) is a known predictor of cardiac events in patients with heart failure, but two-dimensional strain imaging, the reference method to measure myocardial deformation, is not always feasible or available. Therefore, reliable and reproducible alternatives are needed. The aim of the present study was to evaluate unidimensional longitudinal strain (ULS) as a simple echocardiographic parameter for the assessment of LV LF. METHODS: Two hundred two patients with dilated cardiomyopathy who had their first presentation in the authors' cardiology department, as well as the same number of age- and gender-matched control subjects, were prospectively included in this study. ULS was compared with global longitudinal strain (GLS), the current gold standard for LV LF assessment by echocardiography. Uni- and multivariate Cox regression analyses were conducted to evaluate the prognostic value of ULS. RESULTS: LV LF was higher in the control group compared with patients: GLS -19.5 ± 1.7% versus -12.6 ± 4.8% and ULS -16.3 ± 1.5% versus -10.2 ± 3.9% (P < .001 for each). Correlation between ULS and GLS was excellent (r = 0.94), while Bland-Altman plots revealed lower values for ULS (bias -2.76%, limits of agreement ±3.31%). During a mean follow-up time of 39 months, the combined end point of cardiovascular death or hospitalization for acute cardiac decompensation was reached by 28 patients (13.9%). GLS (hazard ratio, 1.21; 95% CI, 1.10-1.34; P < .001) and ULS (hazard ratio, 1.24; 95% CI, 1.12-1.39; P < .001) had comparable prognostic impact on patient outcomes. CONCLUSIONS: ULS might be an alternative echocardiographic method for the assessment of LV LF, with similar diagnostic and prognostic value compared with GLS.


Assuntos
Ecocardiografia/métodos , Insuficiência Cardíaca Sistólica/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Contração Miocárdica/fisiologia , Função Ventricular Esquerda/fisiologia , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca Sistólica/diagnóstico , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
6.
ESC Heart Fail ; 4(3): 232-240, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28772028

RESUMO

AIMS: To compare the performance of the natriuretic peptides (NPs) NT-proBNP and MR-proANP for the diagnosis of acute heart failure (AHF) in subsets of conditions potentially confounding the interpretation of NPs. METHODS AND RESULTS: We studied 312 patients, presenting to the emergency department with new onset of dyspnoea or worsening of chronic dyspnoea within the last 2 weeks. Performance of NPs for the diagnosis of AHF was tested and compared using C-statistics in the entire cohort and in conditions previously described to confound interpretation of NPs such as older age, renal failure, obesity, atrial fibrillation or paced rhythm, and in the NT-proBNP grey zone. AHF was diagnosed in 139 patients. In the entire cohort, the diagnostic performance of NT-proBNP was comparable with that of MR-proANP. Receiver operating characteristic analysis demonstrated that optimal diagnostic cut-offs were higher in the presence of older age, kidney failure or rhythm disorder. However, there were no statistically relevant differences between the receiver operating characteristic curves analysed in the total population and those studied in the pre-specified subsets severe kidney failure, advanced age, obesity, atrial fibrillation and paced rhythm, and grey zone NT-proBNP values. Moreover, the diagnostic performance of NT-proBNP was comparable with that of MR-proANP in the subsets. CONCLUSIONS: The performance of NT-proBNP and MR-proANP for AHF is comparable in the total population as well as in the subsets with potentially confounding characteristics such as older age, renal dysfunction, obesity, atrial fibrillation and paced rhythm, or those with NT-proBNP values in the grey zone.

7.
Eur Heart J Cardiovasc Imaging ; 18(12): 1414-1422, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28165128

RESUMO

Aims: Left ventricular hypertrophy (LVH) has strong prognostic implications and is associated with heart failure. Recently, myocardial contraction fraction (MCF) was identified as a useful marker for specifically identifying cardiac amyloidosis (CA). The purpose of this study was to evaluate the diagnostic accuracy of MCF for the discrimination of different forms of LVH. Methods and results: We analysed cardiovascular magnetic resonance (CMR) scans of patients with CA (n = 132), hypertrophic cardiomyopathy (HCM, n = 60), hypertensive heart disease (HHD, n = 38) and in 100 age- and gender-matched healthy controls. MCF was calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume. The diagnostic accuracy of MCF was compared to that of LV ejection fraction (EF) and the mass index (MI). Compared with controls (136.3 ± 24.4%, P < 0.05), mean values for MCF were significantly reduced in LVH (HHD:92.6 ± 20%, HCM:80 ± 20.3%, transthyretin CA:74.9 ± 32.2% and light-chain (AL) CA:50.5 ± 21.4%). MCF performed better than LVEF (AUC = 0.96 vs. AUC = 0.6, P < 0.001) and was comparable to LVMI (AUC = 0.95, P = 0.4) in discriminating LVH from controls. There was a significant yet weak correlation between MCF and LVEF (r = 0.43, P < 0.0001). MCF outperformed LVEF and LVMI in discriminating between different etiologies of LVH and between AL and other forms of LVH (AUC = 0.84, P < 0.0001). Moreover, cut-off values for MCF <50% and LVEF <60% allowed to identify patients with high probability for CA. Conclusion: In patients with heart failure MCF discriminates CA from other forms of LVH. As it can easily be derived from standard, non-contrast cine images, it may be a very useful marker in the diagnostic workup of patients with LVH.


Assuntos
Insuficiência Cardíaca/diagnóstico por imagem , Hipertensão/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Contração Miocárdica/fisiologia , Fatores Etários , Amiloidose/diagnóstico por imagem , Amiloidose/epidemiologia , Amiloidose/fisiopatologia , Área Sob a Curva , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Diagnóstico Diferencial , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Hospitais Universitários , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Prognóstico , Curva ROC , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Fatores Sexuais , Volume Sistólico/fisiologia
8.
Int J Cardiovasc Imaging ; 33(5): 721-729, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28110433

RESUMO

Cardiac valve plane displacement (CVPD) reflects longitudinal LV function. The purpose of the present study was to determine regional heterogeneity of CVPD in healthy adults to provide normal values by cardiac magnetic resonance (CMR). We measured the anterior aortic plane systolic excursion (AAPSE); the anterior, anterolateral, inferolateral, inferior, and inferoseptal mitral annular plane systolic excursion (MAPSE); and the lateral tricuspid annulus plane systolic excursion (TAPSE). Systolic excursion was measured as the distance from peak end-diastolic to peak end-sysstolic annular position (peak-to-peak) in cine images acquired in 2-, 3- and 4-chamber views. Echocardiographic measurements of CVPD were performed in M-Mode as previously described. We retrospectively analyzed 209 healthy Caucasians (57% men), who participated in the Heidelberg normal cohort between March 2009 and September 2014. The analysis was possible in all participants. Mean values were: AAPSE = 14 ± 3 mm (8-20); MAPSEanterior = 14 ± 3 mm (8-20); MAPSEanterolateral = 16 ± 3 mm (10-22); MAPSEinferolateral = 16 ± 3 mm (10-22); MAPSEinferior = 17 ± 3 mm (11-23); MAPSEinferoseptal = 13 ± 3 mm (7-19) and TAPSE = 26 ± 4 mm (18-34) respectively. MAPSE was significantly elevated in lateral compared to septal regions (p = 0.0001). Sex-differences for CVPD were not found. Age-dependency of CVPD revealed distinct regional differences. AAPSE decreased the most with age (B=-0.48; p = 0.0001), whereas MAPSEinferior was the least age-dependent site (B=-0.17; p = 0.01). AAPSE revealed favorable intra-/interobserver reproducibility and interstudy agreement. Intermethod-comparison of CMR and M-Mode echocardiography showed good agreement between both measurements of CVPD. Age-stratified normal values of regional CVPD are provided. AAPSE revealed the most pronounced age-related decrease and provided favorable reproducibility compared to other regions of cardiac valve plane.


Assuntos
Valva Aórtica/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Valva Mitral/diagnóstico por imagem , Valva Tricúspide/diagnóstico por imagem , Função Ventricular Esquerda , Adulto , Distribuição por Idade , Valva Aórtica/fisiologia , Ecocardiografia , Grupo com Ancestrais do Continente Europeu , Feminino , Alemanha , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiologia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Valva Tricúspide/fisiologia
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