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1.
Int J Cardiol ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35026340

RESUMO

BACKGROUND: Perioperative myocardial infarction/injury (PMI) is a frequent, often missed and incompletely understood complication of noncardiac surgery. The aim of this study was to evaluate whether patient- or procedure-related factors are more strongly associated to the development of PMI in patients undergoing repeated noncardiac surgery. METHODS: In this prospective observational study, patient- and procedure-related factors were evaluated for contribution to PMI using: 1) logistic regression modelling with PMI as primary endpoint, 2) evaluation of concordance of PMI occurrence in the first and the second noncardiac surgery (surgery 1 and 2). and 3) the correlation of the extent of cardiomyocyte injury quantified by high-sensitivity cardiac troponin T between surgery 1 and 2. The secondary endpoint was all-cause mortality associated with PMI reoccurrence in surgery 2. RESULTS: Among 784 patients undergoing repeated noncardiac surgery (in total 1'923 surgical procedures), 116 patients (14.8%) experienced PMI during surgery 1. Among these, PMI occurred again in surgery 2 in 35/116 (30.2%) patients. However, the vast majority of patients developing PMI during surgery 2 (96/131, 73.3%) had not developed PMI during surgery 1 (phi-coefficient 0.150, p < 0.001). The correlation between the extent of cardiomyocyte injury occurring during surgery 1 and 2 was 0.153. All-cause mortality following a second PMI in surgery 2 was dependent on time since surgery (adjusted hazard ratio 5.6 within 30 days and 2.4 within 360 days). CONCLUSIONS: In high-risk patients, procedural factors are more strongly associated with occurrence of PMI than patient factors, but patient factors are also contributors to the occurrence of PMI.

2.
Swiss Med Wkly ; 151: w30103, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34874013

RESUMO

STUDY AIMS: To quantify mimics and chameleons of coronavirus disease 2019 (COVID-19), to analyse the diagnostic accuracy of the triage protocol, and to describe the resulting groups of mimics and chameleons - including their presenting symptoms and final diagnoses. METHODS: Diagnostic accuracy study including all adult patients tested for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) at the emergency department of the University Hospital Basel, Switzerland during the first wave of pandemic in spring 2020. Diagnostic accuracy of triage was determined by calculating sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio. Triage to the group of suspected (+) and not suspected (-) COVID-19 was considered the index test, whereas a SARS-CoV-2 polymerase chain reaction test result was used as reference standard. Mimics were defined as false positives and chameleons as false negatives. RESULTS: Of 2898 patients included in the analysis, 191 were true positives, 895 were false positives (mimics), 9 were false negatives (chameleons) and 1803 were true negatives. This resulted in a sensitivity of 0.95 (95% confidence interval [CI] 0.92-0.98) and a specificity of 0.67 (95% CI 0.65-0.69) for standardised triage. Among mimics, the main categories of final diagnoses were other infections (n = 513, 57.3%), cardiovascular diseases (excluding cerebrovascular) (n = 125, 14%), and non-infectious diseases of the respiratory system (n = 84, 9.4%). Fever (n = 357, 39.9% vs n = 104, 54.5%), cough (n = 466, 52.1% vs n = 126 66%), and smell or taste dysfunction (n = 60, 6.7% vs n = 24, 12.6%) were less frequently observed in mimics than in COVID-19 patients. Eight of nine COVID-19 chameleons presented with either nonspecific complaints (weakness and/or fatigue) or gastrointestinal symptoms. CONCLUSION: The quantitative assessment of COVID-19 mimics and chameleons showed a high prevalence of mimics. Clinical differentiation between true positives and false positives is not feasible due to largely overlapping symptoms. Prevalence of chameleons was very low.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34849666

RESUMO

AIMS: Little is known about the epidemiology, clinical presentation, management, and outcome of acute pericarditis and myopericarditis. METHODS AND RESULTS: The final diagnoses of acute pericarditis, myopericarditis, and non-ST-segment elevation myocardial infarction (NSTEMI) of patients presenting to seven emergency departments in Switzerland with acute chest pain were centrally adjudicated by two independent cardiologists using all information including serial measurements of high-sensitivity cardiac troponin T. The overall incidence of pericarditis and myopericarditis was estimated relative to the established incidence of NSTEMI. Current management and long-term outcome of both conditions were also assessed. Among 2533 chest pain patients, the incidence of pericarditis, myopericarditis, and NSTEMI were 1.9% (n = 48), 1.1% (n = 29), and 21.6% (n = 548), respectively. Accordingly, the estimated incidence of pericarditis and myopericarditis in Switzerland was 10.1 [95% confidence interval (95% CI) 9.3-10.9] and 6.1 (95% CI 5.6-6.7) cases per 100 000 population per year, respectively, vs. 115.0 (95% CI 112.3-117.6) cases per 100 000 population per year for NSTEMI. Pericarditis (85% male, median age 46 years) and myopericarditis (62% male, median age 56 years) had male predominance, and commonly (50% and 97%, respectively) resulted in hospitalization. No patient with pericarditis or myopericarditis died or had life-threatening arrhythmias within 30 days [incidence 0% (95% CI 0.0-4.8%)]. Compared with NSTEMI, the 2-year all-cause mortality adjusted hazard ratio of pericarditis and myopericarditis was 0.40 (95% CI 0.05-2.96), being 0.59 (95% CI 0.40-0.88) for non-cardiac causes of chest pain. CONCLUSION: Pericarditis and myopericarditis are substantially less common than NSTEMI and have an excellent short- and long-term outcome. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, number NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587.

4.
ESC Heart Fail ; 8(2): 1717-1721, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34596976

RESUMO

AIMS: Concern has been raised that treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the expression of angiotensin-converting enzyme 2 (ACE2), which acts as the entry receptor for SARS-CoV-2, and lead to an increased risk of death from SARS-CoV-2. We aimed to address this concern by evaluating the in vivo relationship of treatment with ACE inhibitors and angiotensin receptor blockers (ARB) with circulating plasma concentrations of ACE2 in a large cohort of patients with established cardiovascular disease (n = 1864) or cardiovascular risk factors (n = 2144) but without a history of heart failure. METHODS AND RESULTS: Angiotensin-converting enzyme 2 was measured in 4008 patients (median age 68, 33% women, 31% on ACE-inhibitors, 31% on ARB) using the SOMAscan proteomic platform (SomaLogic Inc, Colorado, USA). Plasma concentration of ACE2 was comparable in 1250 patients on ACE inhibitors (mean 5.99) versus patients without ACE inhibitors (mean 5.98, P = 0.54). Similarly, plasma concentration of ACE2 was comparable in 1260 patients on ARB (mean 5.99) versus patients without ARB (mean 5.98, P = 0.50). Plasma concentration of ACE2 was comparable in 2474 patients on either ACE inhibitors or ARB (mean 5.99) versus patients without ACE inhibitors or ARB (mean 5.98, P = 0.31). Multivariable quantile regression model analysis confirmed the lack of association between treatment with ACE inhibitors or ARB and ACE2 concentrations. Body mass index showed the only positive association with ACE2 plasma concentration (effect 0.015, 95% confidence interval 0.002 to 0.028, P = 0.024). CONCLUSIONS: In a large cohort of patients with established cardiovascular disease or cardiovascular risk factors but without heart failure, ACE inhibitors and ARB were not associated with higher plasma concentrations of ACE2.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Idoso , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Feminino , Humanos , Masculino , Proteômica , Sistema Renina-Angiotensina , SARS-CoV-2
5.
Artigo em Inglês | MEDLINE | ID: mdl-34195803

RESUMO

AIMS: To directly compare the diagnostic accuracy of high-sensitivity cardiac troponin (hs-cTn) T vs. hs-cTnI in the early non-invasive differentiation of Type 1 myocardial infarction (T1MI) due to plaque rupture and atherothrombosis from Type 2 myocardial infarction (T2MI) due to supply-demand mismatch. METHODS AND RESULTS: In a prospective multicentre diagnostic study, two independent cardiologists centrally adjudicated the final diagnosis of T1MI vs. T2MI according to the fourth universal definition of myocardial infarction (MI), using all available clinical information including cardiac imaging in patients presenting with acute chest pain. Diagnostic accuracy was quantified by the area under the receiver operating characteristics curve (AUC). The most extensively validated hs-cTnT-Elecsys and hs-cTnI-Architect assays were measured at presentation, 1 h, and 2 h. Among 5887 patients, 1106 (19%) had a final diagnosis of MI, including 860 (78%) T1MI and 246 (22%) T2MI. The AUC of hs-cTnT-Elecsys to differentiate T1MI from T2MI was moderate and comparable to that provided by hs-cTnI-Architect: hs-cTnT-Elecsys AUC-presentation 0.67 [95% confidence interval (CI) 0.64-0.71], AUC-1 h 0.70 (95% CI 0.66-0.74), and AUC-2 h 0.71 (95% CI 0.66-0.75) vs. hs-cTnI-Architect AUC-presentation 0.71 (95% CI 0.67-0.74), AUC-1 h 0.72 (95% CI 0.68-0.76), and AUC-2 h 0.74 (95% CI 0.69-0.78), all P = not significant (NS). Similarly, the AUC of absolute changes was moderate and comparable for hs-cTnT-Elecsys and hs-cTnI-Architect (all P = NS). Cut-off concentrations achieving at least 90% specificity for the differentiation of T1MI vs. T2MI were >114 ng/L for hs-cTnT-Elecsys [odds ratio (OR) 4.2, 95% CI 2.7-6.6] and >371 ng/L for hs-cTnI-Architect (OR 4.0, 95% CI 2.6-6.2). CONCLUSION: hs-cTnT-Elecsys and hs-cTnI-Architect provided comparable, albeit only moderate, diagnostic accuracy for the early differentiation of T1MI vs. T2MI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587.

6.
Clin Res Cardiol ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34302189

RESUMO

BACKGROUND: Quantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity. METHODS: This was a prospective multicentre study. AHF diagnosis and phenotype were centrally adjudicated by two independent cardiologists among patients presenting to the emergency department with acute dyspnoea. Adrenomedullin system activity was quantified using the biologically active component, bioactive adrenomedullin (bio-ADM), and a prohormone fragment, midregional proadrenomedullin (MR-proADM). Bio-ADM and MR-proADM concentrations were measured in a blinded fashion at presentation and at discharge. Interaction with specific treatments at discharge and the utility of these biomarkers on predicting outcomes during 365-day follow-up were assessed. RESULTS: Among 1886 patients with adjudicated AHF, 514 patients (27.3%) died during 365-day follow-up. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/mL) derived disproportional benefit if treated with diuretics (interaction p values < 0.001). These findings were confirmed when quantifying adrenomedullin system activity using MR-proADM (n = 764) (interaction p values < 0.001). Patients with bio-ADM plasma concentrations above the median were at increased risk of death (hazard ratio 1.87, 95% CI 1.57-2.24; p < 0.001). For predicting 365-day all-cause mortality, both biomarkers performed well, with MR-proADM presenting an even higher predictive accuracy compared to bio-ADM (p < 0.001). CONCLUSIONS: Quantifying the adrenomedullin's system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF.

7.
J Clin Med ; 10(11)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070339

RESUMO

Previous studies have indicated an association between coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI) but lacked a control group. The prospective observational COronaVIrus-surviVAl (COVIVA) study performed at the University Hospital, Basel, Switzerland consecutively enrolled patients with symptoms suggestive of COVID-19. We compared patients who tested positive for SARS-CoV-2 with patients who tested negative but with an adjudicated diagnosis of a respiratory tract infection, including pneumonia. The primary outcome measure was death at 30 days, and the secondary outcomes were AKI incidence and a composite endpoint of death, intensive care treatment or rehospitalization at 30 days. Five hundred and seven patients were diagnosed with respiratory tract infections, and of those, 183 (36%) had a positive PCR swab test for SARS-CoV-2. The incidence of AKI was higher in patients with COVID-19 (30% versus 12%, p < 0.001), more severe (KDIGO stage 3, 22% versus 13%, p = 0.009) and more often required renal replacement therapy (4.4% versus 0.93%; p = 0.03). The risk of 30-day mortality and a composite endpoint was higher in patients with COVID-19-associated AKI (adjusted hazard ratio (aHR) mortality 3.98, 95% confidence interval (CI) 1.10-14.46, p = 0.036; composite endpoint aHR 1.84, 95% CI 1.02-3.31, p = 0.042). The mortality risk was attenuated when adjusting for disease severity (aHR 3.60, 95% CI 0.93-13.96, p = 0.062). AKI occurs more frequently and with a higher severity in patients with COVID-19 and is associated with worse outcomes.

8.
JAMA Cardiol ; 6(7): 771-780, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33881449

RESUMO

Importance: Rapid and accurate noninvasive discrimination of type 2 myocardial infarction (T2MI), which is because of a supply-demand mismatch, from type 1 myocardial infarction (T1MI), which arises via plaque rupture, is essential, because treatment differs substantially. Unfortunately, this is a major unmet clinical need, because even high-sensitivity cardiac troponin (hs-cTn) measurement provides only modest accuracy. Objective: To test the hypothesis that novel cardiovascular biomarkers quantifying different pathophysiological pathways involved in T2MI and/or T1MI may aid physicians in the rapid discrimination of T2MI vs T1MI. Design, Setting, and Participants: This international, multicenter prospective diagnostic study was conducted in 12 emergency departments in 5 countries (Switzerland, Spain, Italy, Poland, and the Czech Republic) with patients presenting with acute chest discomfort to the emergency departments. The study quantified the discrimination of hs-cTn T, hs-cTn I, and 17 novel cardiovascular biomarkers measured in subsets of consecutively enrolled patients against a reference standard (final diagnosis), centrally adjudicated by 2 independent cardiologists according to the fourth universal definition of MI, using all information, including cardiac imaging and serial measurements of hs-cTnT or hs-cTnI. Results: Among 5887 patients, 1106 (18.8%) had an adjudicated final diagnosis of MI; of these, 860 patients (77.8%) had T1MI, and 246 patients (22.2%) had T2MI. Patients with T2MI vs those with T1MI had lower concentrations of biomarkers quantifying cardiomyocyte injury hs-cTnT (median [interquartile range (IQR)], 30 (17-55) ng/L vs 58 (28-150) ng/L), hs-cTnI (median [IQR], 23 [10-83] ng/L vs 115 [28-576] ng/L; P < .001), and cardiac myosin-binding protein C (at presentation: median [IQR], 76 [38-189] ng/L vs 257 [75-876] ng/L; P < .001) but higher concentrations of biomarkers quantifying endothelial dysfunction, microvascular dysfunction, and/or hemodynamic stress (median [IQR] values: C-terminal proendothelin 1, 97 [75-134] pmol/L vs 68 [55-91] pmol/L; midregional proadrenomedullin, 0.97 [0.67-1.51] pmol/L vs 0.72 [0.53-0.99] pmol/L; midregional pro-A-type natriuretic peptide, 378 [207-491] pmol/L vs 152 [90-247] pmol/L; and growth differentiation factor 15, 2.26 [1.44-4.35] vs 1.56 [1.02-2.19] ng/L; all P < .001). Discrimination for these biomarkers, as quantified by the area under the receiver operating characteristics curve, was modest (hs-cTnT, 0.67 [95% CI, 0.64-0.71]; hs-cTn I, 0.71 [95% CI, 0.67-0.74]; cardiac myosin-binding protein C, 0.67 [95% CI, 0.61-0.73]; C-terminal proendothelin 1, 0.73 [95% CI, 0.63-0.83]; midregional proadrenomedullin, 0.66 [95% CI, 0.60-0.73]; midregional pro-A-type natriuretic peptide, 0.77 [95% CI, 0.68-0.87]; and growth differentiation factor 15, 0.68 [95% CI, 0.58-0.79]). Conclusions and Relevance: In this study, biomarkers quantifying myocardial injury, endothelial dysfunction, microvascular dysfunction, and/or hemodynamic stress provided modest discrimination in early, noninvasive diagnosis of T2MI.

9.
Horm Behav ; 131: 104967, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33862349

RESUMO

The time of dominance rank acquisition is a crucial phase in male life history that often affects reproductive success and hence fitness. Hormones such as testosterone and glucocorticoids can influence as well as be affected by this process. At the same time, hormone concentrations can show large individual variation. The extent to which such variation is repeatable, particularly in dynamic social settings, is a question of current interest. The aim of the present study was therefore to investigate how dominance rank and individual differences contribute to variance in hormone concentrations during male rank acquisition in a complex social environment. For this purpose, dominance rank as well as baseline testosterone, baseline cortisol, and cortisol responsiveness after exposure to a novel environment were determined in colony-housed guinea pig males from late adolescence through adulthood. Hormone-dominance relationships and repeatability of hormone measures beyond their relation to rank were assessed. There was a significant positive relationship between baseline testosterone and rank, but this link became weaker with increasing age. Baseline cortisol or cortisol responsiveness, in contrast, were not significantly related to dominance. Notably, all three endocrine parameters were significantly repeatable independent of dominance rank from late adolescence through adulthood. Baseline testosterone and cortisol responsiveness showed a significantly higher repeatability than baseline cortisol. This suggests that testosterone titres and cortisol responsiveness represent stable individual attributes even under complex social conditions.


Assuntos
Hidrocortisona , Individualidade , Animais , Cobaias , Masculino , Fenótipo , Predomínio Social , Meio Social , Testosterona
10.
Eur Heart J Acute Cardiovasc Care ; 10(7): 746-755, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33620434

RESUMO

AIMS: Diagnosis of acute myocardial infarction (AMI) can be challenging in patients with prior coronary artery bypass grafting (CABG). METHODS AND RESULTS: Final diagnoses were adjudicated by two independent cardiologists using the universal definition of AMI among patients presenting to the emergency department (ED) with suspected AMI. Diagnostic accuracy of 34 chest pain characteristics (CPCs) and four electrocardiogram (ECG) signatures stratified according to the presence or absence of prior CABG were prospectively quantified. Among 4015 patients (no prior CABG: n = 3686; prior CABG: n = 329), prevalence of AMI and unstable angina were higher in patients with prior CABG (35% vs. 18%; 26% vs. 8%; both P < 0.001). Three CPCs (9%) and two electrocardiographic findings (50%) showed a different diagnostic performance (interaction P < 0.05) with loss of diagnostic value in patients with prior CABG. The diagnostic accuracy as quantified by the area under the curve (AUC) of the integrated clinical judgement was moderate to good in patients with prior CABG, and significantly lower compared to patients without prior CABG [AUC 0.80 (95% confidence interval (CI) 0.75-0.84) vs. AUC 0.87 (95% CI 0.86-0.89); P = 0.004]. Time to discharge from the ED was significantly longer in patients with prior CABG [359 (215-525) min vs. 300 (192-435) min; P < 0.001]. Key findings were confirmed in a large independent external validation cohort (n = 13 653). CONCLUSIONS: Patients with prior CABG presenting with suspected AMI have a high prevalence of AMI and unstable angina and lower diagnostic accuracy of CPCs and the ECG, possibly justifying liberal use of early coronary angiography in these vulnerable patients. CLINICALTRIALS.GOV REGISTRY: Number NCT00470587.


Assuntos
Ponte de Artéria Coronária , Infarto do Miocárdio , Angina Instável , Dor no Peito , Eletrocardiografia , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia
11.
Eur J Heart Fail ; 23(5): 716-725, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33421273

RESUMO

AIMS: Cardiac myosin-binding protein C (cMyC) seems to be even more sensitive in the quantification of cardiomyocyte injury vs. high-sensitivity cardiac troponin, and may therefore have diagnostic and prognostic utility. METHODS AND RESULTS: In a prospective multicentre diagnostic study, cMyC, high-sensitivity cardiac troponin T (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma concentrations were measured in blinded fashion in patients presenting to the emergency department with acute dyspnoea. Two independent cardiologists centrally adjudicated the final diagnosis. Diagnostic accuracy for acute heart failure (AHF) was quantified by the area under the receiver operating characteristic curve (AUC). All-cause mortality within 360 days was the prognostic endpoint. Among 1083 patients eligible for diagnostic analysis, 51% had AHF. cMyC concentrations at presentation were higher among AHF patients vs. patients with other final diagnoses [72 (interquartile range, IQR 39-156) vs. 22 ng/L (IQR 12-42), P < 0.001)]. cMyC's AUC was high [0.81, 95% confidence interval (CI) 0.78-0.83], higher than hs-cTnT's (0.79, 95% CI 0.76-0.82, P = 0.081) and lower than NT-proBNP's (0.91, 95% CI 0.89-0.93, P < 0.001). Among 794 AHF patients eligible for prognostic analysis, 28% died within 360 days; cMyC plasma concentrations above the median indicated increased risk of death (hazard ratio 2.19, 95% CI 1.66-2.89; P < 0.001). cMyC's prognostic accuracy was comparable with NT-proBNP's and hs-cTnT's. cMyC did not independently predict all-cause mortality when used in validated multivariable regression models. In novel multivariable regression models including medication, age, left ventricular ejection fraction, and discharge creatinine, cMyC remained an independent predictor of death and had no interactions with medical therapies at discharge. CONCLUSION: Cardiac myosin-binding protein C may aid physicians in the rapid triage of patients with suspected AHF.


Assuntos
Insuficiência Cardíaca , Biomarcadores , Proteínas de Transporte , Proteínas de Ligação a DNA , Humanos , Peptídeo Natriurético Encefálico , Peptídeo Natriurético Tipo C , Fragmentos de Peptídeos , Prognóstico , Estudos Prospectivos , Medição de Risco , Volume Sistólico , Fatores de Transcrição , Troponina T , Função Ventricular Esquerda
12.
Heart ; 107(22): 1796-1804, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33504514

RESUMO

OBJECTIVE: To develop an ECG-based tool for rapid risk assessment of a cardiac cause of syncope in patients ≥40 years. METHODS: In a prospective international multicentre study, 2007 patients ≥40 years presenting with syncope were recruited in the emergency department (ED) of participating centres ranging from large university hospitals to smaller rural hospitals in eight countries from May 2010 to July 2017. 12-Lead ECG recordings were obtained at ED presentation following the syncopal event. The primary diagnostic outcome, a cardiac cause of syncope, was centrally adjudicated by two independent cardiologists using all available clinical information including 12-month follow-up. ECG predictors for a cardiac cause of syncope were identified using penalised backward selection and a continuous-scale likelihood was calculated based on regression analysis coefficients. Findings were validated in an independent US multicentre cohort including 2269 patients. RESULTS: In the derivation cohort, a cardiac cause of syncope was adjudicated in 267 patients (16%). Seven ECG criteria were identified as predictors for this outcome: heart rate and QTc-interval (continuous predictors), rhythm, atrioventricular block, ST-segment depression, bundle branch block and ventricular extrasystole/non-sustained ventricular tachycardia (categorical predictors). Diagnostic accuracy of these combined predictors for a cardiac cause of syncope was high (area under the curve 0.80, 95% CI 0.77 to 0.83). Overall, 138 patients (8%) were rapidly triaged towards rule-out and 181 patients (11%) towards rule-in of a cardiac cause of syncope. External validation showed similar performance. CONCLUSION: In patients ≥40 years with a syncopal event, a combination of seven ECG criteria enabled rapid assessment of the likelihood that syncope was due to a cardiac cause. TRIAL REGISTRATION NUMBER: NCT01548352 (BASEL IX), NCT01802398 (SRS study).

13.
Rev Esp Cardiol (Engl Ed) ; 74(6): 502-509, 2021 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32451223

RESUMO

INTRODUCTION AND OBJECTIVES: Release kinetics of high-sensitivity cardiac troponin (hs-cTn) T and I in patients with acute myocardial infarction (AMI) are incompletely understood. We aimed to assess whether hs-cTnT/I release in early AMI is near linear. METHODS: In a prospective diagnostic multicenter study the acute release of hs-cTnT and hs-cTnI within 1 and 2hours from presentation to the emergency department was quantified using 3 hs-cTnT/I assays in patients with suspected AMI. The primary endpoint was correlation between hs-cTn changes from presentation to 1 hour vs changes from presentation to 2hours, among all AMI patients and different prespecified subgroups. The final diagnosis was adjudicated by 2 independent cardiologists, based on serial hs-cTnT from the serial study blood samples and additional locally measured hs-cTn values. RESULTS: Among 2437 patients with complete hs-cTnT data, AMI was the adjudicated diagnosis in 376 patients (15%). For hs-cTnT, the correlation coefficient between 0- to 1-hour change and 0- to 2 hour change was 0.931 (95%CI, 0.916-0.944), P <.001. Similar findings were obtained with hs-cTnI (Architect) with correlation coefficients between 0- to 1-hour change and 0- to 2 hour change of 0.969 and hs-cTnI (Centaur) of 0.934 (P <.001 for both). Findings were consistent among type 1 and type 2 AMI and in the subgroup of patients presenting very early after chest pain onset. CONCLUSIONS: Patients presenting with early AMI showed a near linear release of hs-cTnT and hs-cTnI. This near linearity provides the pathophysiological basis for rapid diagnostic algorithms using 0- to 1-hour changes as surrogates for 0- to 2 hour or 0- to 3 hour changes. Registered at ClinicalTrials.gov (Identifier: NCT00470587).


Assuntos
Infarto do Miocárdio , Troponina T , Biomarcadores , Humanos , Cinética , Infarto do Miocárdio/diagnóstico , Estudos Prospectivos , Troponina I
14.
J Am Chem Soc ; 142(52): 21712-21719, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33346654

RESUMO

Direct valorization of ethane, a substantial component of shale gas deposits, at mild conditions remains a significant challenge, both from an industrial and an academic point of view. Herein, we report iodine as an efficient and selective catalyst for the functionalization of ethane in oleum at low temperatures and pressures. A thorough study of relevant reaction parameters revealed iodine to be remarkably more active than the previously reported "Periana/Catalytica" catalyst under optimized conditions. As a result of a fundamentally different catalytic cycle, iodine yields the bis-bisulfate ester of ethylene glycol (HO3SO-CH2-CH2-OSO3H, EBS), whereas for state-of-the-art platinum-based catalysts ethionic acid (HO3S-CH2-CH2-OSO3H, ETA) is obtained as the main product. Our findings open up an attractive route for the direct conversion of ethane toward ethylene glycol.

16.
Europace ; 22(12): 1885-1895, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33038231

RESUMO

AIMS: The aim of this study is to characterize recurrent syncope, including sex-specific aspects, and its impact on death and major adverse cardiovascular events (MACE). METHODS AND RESULTS: We characterized recurrent syncope in a large international multicentre study, enrolling patients ≥40 years presenting to the emergency department (ED) with a syncopal event within the last 12 h. Syncope aetiology was centrally adjudicated by two independent cardiologists using all information becoming available during syncope work-up and long-term follow-up. Overall, 1790 patients were eligible for this analysis. Incidence of recurrent syncope was 20% [95% confidence interval (CI) 18-22%] within the first 24 months. Patients with an adjudicated final diagnosis of cardiac syncope (hazard ratio (HR) 1.50, 95% CI 1.11-2.01) or syncope with an unknown aetiology even after central adjudication (HR 2.11, 95% CI 1.54-2.89) had an increased risk for syncope recurrence. Least Absolute Shrinkage and Selection Operator regression fit on all patient information available early in the ED identified >3 previous episodes of syncope as the only independent predictor for recurrent syncope (HR 2.13, 95% CI 1.64-2.75). Recurrent syncope carried an increased risk for death (HR 1.87, 95% CI 1.26-2.77) and MACE (HR 2.69, 95% CI 2.02-3.59) over 24 months of follow-up, however, with a time-dependent effect. These findings were confirmed in a sensitivity analysis excluding patients with syncope recurrence or MACE before or during ED evaluation. CONCLUSION: Recurrence rates of syncope are substantial and vary depending on syncope aetiology. Importantly, recurrent syncope carries a time-dependent increased risk for death and MACE. TRIAL REGISTRATION: BAsel Syncope EvaLuation (BASEL IX, ClinicalTrials.gov registry number NCT01548352).


Assuntos
Serviço Hospitalar de Emergência , Síncope , Feminino , Humanos , Incidência , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Síncope/diagnóstico , Síncope/epidemiologia
17.
Eur Respir J ; 56(5)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32616594

RESUMO

While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV), cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use.We elucidated the molecular mechanisms by which the cyclophilin inhibitors cyclosporin A (CsA) and alisporivir (ALV) restrict MERS-CoV to validate their suitability as readily available therapy in MERS-CoV infection.Calu-3 cells and primary human alveolar epithelial cells (hAECs) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including calcineurin, nuclear factor of activated T-cells (NFATs) or mitogen-activated protein kinases. Novel CsA-induced pathways were identified by RNA sequencing and manipulated by gene knockdown or neutralising antibodies. Viral replication was quantified by quantitative real-time PCR and 50% tissue culture infective dose. Data were validated in a murine MERS-CoV infection model.Both CsA and ALV reduced MERS-CoV titres and viral RNA replication in Calu-3 cells and hAECs, improving epithelial integrity. While neither calcineurin nor NFAT inhibition reduced MERS-CoV propagation, blockade of c-Jun N-terminal kinase diminished infectious viral particle release but not RNA accumulation. Importantly, CsA induced interferon regulatory factor 1 (IRF1), a pronounced type III interferon (IFNλ) response and expression of antiviral genes. Downregulation of IRF1 or IFNλ increased MERS-CoV propagation in the presence of CsA. Importantly, oral application of CsA reduced MERS-CoV replication in vivo, correlating with elevated lung IFNλ levels and improved outcome.We provide evidence that cyclophilin inhibitors efficiently decrease MERS-CoV replication in vitro and in vivo via upregulation of inflammatory antiviral cell responses, in particular IFNλ. CsA might therefore represent a promising candidate for treating MERS-CoV infection.


Assuntos
Infecções por Coronavirus/prevenção & controle , Ciclofilinas/antagonistas & inibidores , Ciclosporina/farmacologia , Interferons/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/virologia , Animais , Inibidores de Calcineurina/farmacologia , Técnicas de Cultura de Células , Infecções por Coronavirus/metabolismo , Modelos Animais de Doenças , Humanos , Fator Regulador 1 de Interferon/efeitos dos fármacos , Fator Regulador 1 de Interferon/metabolismo , Interferons/efeitos dos fármacos , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Replicação Viral/efeitos dos fármacos
18.
Proc Biol Sci ; 287(1928): 20200667, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32517608

RESUMO

Phenotypic plasticity allows individuals to adjust traits to the environment. Whether long-term adjustments of the phenotype occur during later life stages is largely unknown. To address this question, we examined whether hormonal phenotypes that are shaped by the environment during adolescence can still be reshaped in full adulthood. For this, guinea pig males were either housed in mixed-sex colonies or in heterosexual pairs. In adulthood, males were individually transferred to pair housing with a female. This way, a social niche transition was induced in colony-housed males, but not in pair-housed males. Before transfer, corresponding to findings in adolescence, adult colony-housed males showed significantly higher baseline testosterone levels and lower cortisol responsiveness than pair-housed males. One month after transfer, the hormonal phenotype of colony-housed males was changed towards that of pair-housed males: animals showed comparable baseline testosterone levels and cortisol responsiveness was significantly increased in colony-housed males. This endocrine readjustment builds the basis for an adaptive behavioural tactic in the new social situation. Thus, an adaptive change of the behavioural phenotype may still occur in adulthood via modification of underlying mechanisms. This suggests a greater role for developmental plasticity in later life stages than is commonly presumed.


Assuntos
Adaptação Psicológica , Comportamento Social , Animais , Feminino , Cobaias , Masculino , Meio Social , Testosterona
19.
ESC Heart Fail ; 7(4): 1817-1829, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32452635

RESUMO

AIMS: The aim of this study was to investigate the diagnostic and prognostic utility of the QRS-T angle, an electrocardiogram (ECG) marker quantifying depolarization-repolarization heterogeneity, in patients with suspected acute decompensated heart failure (ADHF). METHODS AND RESULTS: We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of ADHF. The QRS-T angle was automatically derived from a standard 12-lead ECG recorded at presentation. The primary diagnostic endpoint was a final adjudicated diagnosis of ADHF. The primary prognostic endpoint was all-cause mortality during 2 years of follow-up. Among the 1915 patients enrolled, those with higher QRS-T angles were older, were more commonly male, and had a higher rate of co-morbidities such as arterial hypertension, coronary artery disease, or chronic kidney disease. ADHF was the final adjudicated diagnosis in 1140 (60%) patients. The QRS-T angle in patients with ADHF was significantly larger than in patients with non-cardiac causes of dyspnoea {median 110° [inter-quartile range (IQR) 46-156°] vs. median 33° [IQR 15-57°], P < 0.001}. The diagnostic accuracy of the QRS-T angle as quantified by the area under the receiver operating characteristic curve (AUC) was 0.75 [95% confidence interval (CI) 0.73-0.77, P < 0.001], which was inferior to N-terminal pro-B-type natriuretic peptide (AUC 0.93, 95% CI 0.92-0.94, P < 0.001), but similar to that of high-sensitivity troponin T (AUC 0.78, 95% CI 0.76-0.80, P = 0.09). The AUC of the QRS-T angle for discrimination between ADHF and non-cardiac dyspnoea remained similarly high in subgroups of patients known to be diagnostically challenging, including patients older than 75 years [0.71 (95% CI 0.67-0.74)], renal failure [0.79 (95% CI 0.71-0.87)], and atrial fibrillation at presentation [0.68 (95% CI 0.60-0.76)]. Mortality rates according to QRS-T angle tertiles were 4%, 6%, and 10% after 30 days (P < 0.001) and 24%, 31%, and 43% after 2 years (P < 0.001). After adjustment for clinical, laboratory, and ECG parameters, the QRS-T angle remained an independent predictor for 2 year mortality with a 4% increase in mortality for every 20° increase in QRS-T angle (P = 0.02). CONCLUSIONS: The QRS-T angle is a readily available and inexpensive marker that can assist in the discrimination between ADHF and non-cardiac causes of acute dyspnoea and may aid in the risk stratification of these patients.


Assuntos
Insuficiência Cardíaca , Arritmias Cardíacas , Dispneia , Eletrocardiografia , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Prognóstico
20.
J Am Coll Cardiol ; 75(10): 1111-1124, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32164884

RESUMO

BACKGROUND: Until now, high-sensitivity cardiac troponin (hs-cTn) assays were mainly developed for large central laboratory platforms. OBJECTIVES: This study aimed to assess the clinical performance of a point-of-care (POC)-hs-cTnI assay in patients with suspected myocardial infarction (MI). METHODS: This study enrolled patients presenting to the emergency department with symptoms suggestive of MI. Two cardiologists centrally adjudicated the final diagnosis using all clinical data including cardiac imaging. The primary objective was to directly compare diagnostic accuracy of POC-hs-cTnI-TriageTrue versus best-validated central laboratory assays. Secondary objectives included the derivation and validation of a POC-hs-cTnI-TriageTrue-specific 0/1-h algorithm. RESULTS: MI was the adjudicated final diagnosis in 178 of 1,261 patients (14%). The area under the curve (AUC) for POC-hs-cTnI-TriageTrue at presentation was 0.95 (95% confidence interval [CI]: 0.93 to 0.96) and was at least comparable to hs-cTnT-Elecsys (AUC: 0.94; 95% CI: 0.93 to 0.96; p = 0.213) and hs-cTnI-Architect (AUC: 0.92; 95% CI: 0.90 to 0.93; p < 0.001). A single cutoff concentration <3 ng/l at presentation identified 45% of patients at low risk with a negative predictive value (NPV) of 100% (95% CI: 99.4% to 100%). A single cutoff concentration >60 ng/l identified patients at high risk with a positive predictive value (PPV) of 76.8% (95% CI: 68.9% to 83.6%). The 0/1-h algorithm ruled out 55% of patients (NPV: 100%; 95% CI: 98.8% to 100%), and ruled in 18% of patients (PPV: 76.8%; 95% CI: 67.2% to 84.7%). Ruled-out patients had cumulative event rates of 0% at 30 days and 1.6% at 2 years. This study confirmed these findings in a secondary analysis including hs-cTnI-Architect for central adjudication. CONCLUSIONS: The POC-hs-cTnI-TriageTrue assay provides high diagnostic accuracy in patients with suspected MI with a clinical performance that is at least comparable to that of best-validated central laboratory assays. (Advantageous Predictors of Acute Coronary Syndromes Evaluation Study [APACE]; NCT00470587).


Assuntos
Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Troponina I/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Diagnóstico Precoce , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
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