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1.
Swiss Med Wkly ; 149: w20125, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31656035

RESUMO

Biomarkers are noninvasive, inexpensive, highly reproducible tools that allow clinicians to quantify pathophysiological processes relevant to a specific disease. Although the concept of biomarker-guided precision medicine is still in its infancy once a specific cardiovascular diagnosis is established, biomarker guidance has become the standard of care in the early diagnosis of acute cardiovascular disease in patients presenting to the emergency department with common symptoms such as acute chest pain or acute dyspnoea. This review highlights recent advances and remaining uncertainties regarding the use of the most relevant cardiovascular biomarkers, namely high-sensitivity cardiac troponin and natriuretic peptides in established indications such as the early diagnosis of acute myocardial infarction and heart failure. In addition, we address emerging indications such as the screening for perioperative myocardial infarction.

2.
J Am Coll Cardiol ; 74(6): 744-754, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31395124

RESUMO

BACKGROUND: The prevalence of pulmonary embolism (PE) in patients presenting with syncope to the emergency department (ED) is largely unknown. This information, however, is necessary to balance the potential medical benefit or harm of systematic PE screening in patients presenting with syncope to the ED. OBJECTIVES: This study sought to determine the prevalence of PE in patients with syncope. METHODS: Unselected patients presenting with syncope to the ED were prospectively enrolled in a diagnostic multicenter study. Pre-test clinical probability for PE was assessed using the 2-level Wells score and the results of D-dimer testing using age-adapted cutoffs. Presence of PE was evaluated by imaging modalities, when ordered as part of the clinical assessment by the treating ED physician or by long-term follow-up data. RESULTS: Long-term follow-up was complete in 1,380 patients (99%) at 360 days and 1,156 patients (83%) at 720 days. Among 1,397 patients presenting with syncope to the ED, PE was detected at presentation in 19 patients (1.4%; 95% confidence interval [CI]: 0.87% to 2.11%). The incidence of new PEs or cardiovascular death during 2-year follow-up was 0.9% (95% CI: 0.5% to 1.5%). In the subgroup of patients hospitalized (47%), PE was detected at presentation in 15 patients (2.3%; 95% CI: 1.4% to 3.7%). The incidence of new PEs or cardiovascular death during 2-year follow-up was 0.9% (95% CI: 0.4% to 2.0%). CONCLUSIONS: PE seems to be a rather uncommon cause of syncope among patients presenting to the ED. Therefore, systematic PE-screening in all patients with syncope does not seem warranted. (BAsel Syncope EvaLuation Study [BASEL IX]; NCT01548352).

3.
J Am Coll Cardiol ; 74(7): 842-854, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31416527

RESUMO

BACKGROUND: Early and accurate detection of short-term major adverse cardiac events (MACE) in patients with suspected acute myocardial infarction (AMI) is an unmet clinical need. OBJECTIVES: The goal of this study was to test the hypothesis that adding clinical judgment and electrocardiogram findings to the European Society of Cardiology (ESC) high-sensitivity cardiac troponin (hs-cTn) measurement at presentation and after 1 h (ESC hs-cTn 0/1 h algorithm) would further improve its performance to predict MACE. METHODS: Patients presenting to an emergency department with suspected AMI were enrolled in a prospective, multicenter diagnostic study. The primary endpoint was MACE, including all-cause death, cardiac arrest, AMI, cardiogenic shock, sustained ventricular arrhythmia, and high-grade atrioventricular block within 30 days including index events. The secondary endpoint was MACE + unstable angina (UA) receiving early (≤24 h) revascularization. RESULTS: Among 3,123 patients, the ESC hs-cTnT 0/1 h algorithm triaged significantly more patients toward rule-out compared with the extended algorithm (60%; 95% CI: 59% to 62% vs. 45%; 95% CI: 43% to 46%; p < 0.001), while maintaining similar 30-day MACE rates (0.6%; 95% CI: 0.3% to 1.1% vs. 0.4%; 95% CI: 0.1% to 0.9%; p = 0.429), resulting in a similar negative predictive value (99.4%; 95% CI: 98.9% to 99.6% vs. 99.6%; 95% CI: 99.2% to 99.8%; p = 0.097). The ESC hs-cTnT 0/1 h algorithm ruled-in fewer patients (16%; 95% CI: 14.9% to 17.5% vs. 26%; 95% CI: 24.2% to 27.2%; p < 0.001) compared with the extended algorithm, albeit with a higher positive predictive value (76.6%; 95% CI: 72.8% to 80.1% vs. 59%; 95% CI: 55.5% to 62.3%; p < 0.001). For 30-day MACE + UA, the ESC hs-cTnT 0/1 h algorithm had a higher positive predictive value for rule-in, whereas the extended algorithm had a higher negative predictive value for the rule-out. Similar findings emerged when using hs-cTnI. CONCLUSIONS: The ESC hs-cTn 0/1 h algorithm better balanced efficacy and safety in the prediction of MACE, whereas the extended algorithm is the preferred option for the rule-out of 30-day MACE + UA. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587).

4.
J Am Coll Cardiol ; 74(4): 483-494, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31345421

RESUMO

BACKGROUND: The European Society of Cardiology (ESC) recommends the 0/1-h algorithm for rapid triage of patients with suspected non-ST-segment elevation myocardial infarction (MI). However, its impact on patient management and safety when routinely applied is unknown. OBJECTIVES: This study sought to determine these important real-world outcome data. METHODS: In a prospective international study enrolling patients presenting with acute chest discomfort to the emergency department (ED), the authors assessed the real-world performance of the ESC 0/1-h algorithm using high-sensitivity cardiac troponin T embedded in routine clinical care and its associated 30-day rates of major adverse cardiac events (MACE) (the composite of cardiovascular death and MI). RESULTS: Among 2,296 patients, non-ST-segment elevation MI prevalence was 9.8%. In median, 1-h blood samples were collected 65 min after the 0-h blood draw. Overall, 94% of patients were managed without protocol violations, and 98% of patients triaged toward rule-out did not require additional cardiac investigations including high-sensitivity cardiac troponin T measurements at later time points or coronary computed tomography angiography in the ED. Median ED stay was 2 h and 30 min. The ESC 0/1-h algorithm triaged 62% of patients toward rule-out, and 71% of all patients underwent outpatient management. Proportion of patients with 30-day MACE were 0.2% (95% confidence interval: 03% to 0.5%) in the rule-out group and 0.1% (95% confidence interval: 0% to 0.2%) in outpatients. Very low MACE rates were confirmed in multiple subgroups, including early presenters. CONCLUSIONS: These real-world data document the excellent applicability, short time to ED discharge, and low rate of 30-day MACE associated with the routine clinical use of the ESC 0/1-h algorithm for the management of patients presenting with acute chest discomfort to the ED.

5.
Heart ; 105(20): 1559-1567, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31142594

RESUMO

OBJECTIVE: Patients with suspected acute myocardial infarction (AMI) in the setting of left bundle branch block (LBBB) present an important diagnostic and therapeutic challenge to the clinician. METHODS: We prospectively evaluated the incidence of AMI and diagnostic performance of specific ECG and high-sensitivity cardiac troponin (hs-cTn) criteria in patients presenting with chest discomfort to 26 emergency departments in three international, prospective, diagnostic studies. The final diagnosis of AMI was centrally adjudicated by two independent cardiologists according to the universal definition of myocardial infarction. RESULTS: Among 8830 patients, LBBB was present in 247 (2.8%). AMI was the final diagnosis in 30% of patients with LBBB, with similar incidence in those with known LBBB versus those with presumably new LBBB (29% vs 35%, p=0.42). ECG criteria had low sensitivity (1%-12%) but high specificity (95%-100%) for AMI. The diagnostic accuracy as quantified by the receiver operating characteristics (ROC) curve of hs-cTnT and hs-cTnI concentrations at presentation (area under the ROC curve (AUC) 0.91, 95% CI 0.85 to 0.96 and AUC 0.89, 95% CI 0.83 to 0.95), as well as that of their 0/1-hour and 0/2-hour changes, was very high. A diagnostic algorithm combining ECG criteria with hs-cTnT/I concentrations and their absolute changes at 1 hour or 2 hours derived in cohort 1 (45 of 45(100%) patients with AMI correctly identified) showed high efficacy and accuracy when externally validated in cohorts 2 and 3 (28 of 29 patients, 97%). CONCLUSION: Most patients presenting with suspected AMI and LBBB will be found to have diagnoses other than AMI. Combining ECG criteria with hs-cTnT/I testing at 0/1 hour or 0/2 hours allows early and accurate diagnosis of AMI in LBBB. TRIAL REGISTRATION NUMBER: APACE: NCT00470587; ADAPT: ACTRN12611001069943; TRAPID-AMI: RD001107;Results.

6.
Int J Cardiol ; 292: 1-12, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31056411

RESUMO

BACKGROUND: Rapid and reliable diagnosis of ST-elevation myocardial infarction (STEMI) as a surrogate for acute coronary occlusion is critical for early reperfusion therapy. OBJECTIVES: We aimed to examine the diagnostic performance of current guideline-recommended Electrocardiogram (ECG) STEMI criteria. METHODS: In a prospective diagnostic multicenter study, we objectively quantified the extent of ST-segment elevation in all ECG leads using an automated software-based analysis of the digital 12-lead-ECG in adult patients presenting to the emergency department (ED) with suspected myocardial infarction (MI). Classification according to current guideline-recommended ECG criteria for STEMI at ED presentation was compared against a final diagnosis adjudicated by two independent cardiologists after reviewing all available medical records including serial ECGs, cardiac imaging and coronary angiograms. RESULTS: Among 2486 patients, 52 (2%) were found to have significant ST-segment elevation on ECG at ED presentation according to current guideline-recommended ECG criteria for STEMI. Eighty-one (3%) patients received a final adjudicated diagnosis of STEMI. Only 35% (28 of 81) of all patients with a final diagnosis of STEMI were correctly identified (PPV 54% (95% CI 41-66%), sensitivity 35% (95% Cl 24-46%), NPV 97.8% (95% CI 97.5-98.1%). Four reasons for missing STEMIs emerged: timing (significant STE at an earlier/later time point) in 25%, incorrect measurement points in 30%, non or borderline-significant STE in 36% and inferoposterior MI localisation in 9%. CONCLUSIONS: A computerized analysis of current guideline-recommended ECG criteria for STEMI showed suboptimal diagnostic performance when applied to a single 12­lead ECG performed at ED presentation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.

7.
Heart ; 105(18): 1423-1431, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31018955

RESUMO

OBJECTIVE: Assess the relative incidence and compare characteristics and outcome of unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI). DESIGN: Two independent prospective multicentre diagnostic studies (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] and High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome [High-STEACS]) enrolling patients with acute chest discomfort presenting to the emergency department. Central adjudication of the final diagnosis was done by two independent cardiologists using all clinical information including serial measurements of high-sensitivity cardiac troponin (hs-cTn). All-cause death and future non-fatal MI were assessed at 30 days and 1 year. RESULTS: 8992 patients were enrolled at 11 centres. UA was adjudicated in 8.9%(95% CI 8.0 to 9.7) and 2.8% (95% CI 2.3 to 3.3) patients in APACE and High-STEACS, respectively, and NSTEMI in 15.1% (95% CI 14.0 to 16.2) and 13.4% (95% CI 12.4 to 14.3). Coronary artery disease was pre-existing in 73% and 76% of patients with UA. At 30 days, all-cause mortality in UA was substantially lower as compared with NSTEMI (0.5% vs 3.7%, p=0.002 in APACE, 0.7% vs 7.4%, p=0.004 in High-STEACS). Similarly, at 1 year in UA all-cause mortality was 3.3% (95% CI 1.2 to 5.3) vs 10.4% (95% CI 7.9 to 12.9) in APACE, and 5.1% (95% CI 0.7 to 9.5) vs 22.9% (95% CI 19.3 to 26.4) in High-STEACS, and similar to non-cardiac chest pain (NCCP). In contrast, future non-fatal MI in APACE was comparable in UA and NSTEMI (11.2%, 95% CI 7.8 to 14.6 and 7.9%, 95% CI 5.7 to 10.2), and higher than in NCCP (0.6%, 95% CI 0.2 to 1.0). CONCLUSIONS: The relative incidence and mortality of UA is substantially lower than that of NSTEMI, while the rate of future non-fatal MI is similar.

8.
Eur Heart J Acute Cardiovasc Care ; : 2048872619842988, 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31008655

RESUMO

AIM: Exercise stress testing is used to detect myocardial ischaemia, but is limited by low sensitivity and specificity. The authors investigated the value of the analysis of high-frequency QRS components as a marker of abnormal depolarization in addition to standard ST-deviations as a marker of abnormal repolarization to improve the diagnostic accuracy. METHODS AND RESULTS: Consecutive patients undergoing bicycle exercise stress nuclear myocardial perfusion imaging were prospectively enrolled. Presence of myocardial ischaemia, the primary diagnostic endpoint, was adjudicated using MPI and coronary angiography. Automated high-frequency QRS analysis was performed in a blinded fashion. The prognostic endpoint was major adverse cardiac events (MACEs) during two years of follow-up. Exercise-induced ischaemia was detected in 147/662 patients (22%). The sensitivity of high-frequency QRS was similar to ST-deviations (46% vs. 43%, p=0.59), while the specificity was lower (75% vs. 87%, p<0.001). The combined use of high-frequency QRS and ST-deviations classified 59% of patients as 'rule-out' (both negative), 9% as 'rule-in' (both positive) and 32% in an intermediate zone (one test positive). The sensitivity for 'rule-out' and the specificity for 'rule-in' improved to 63% and 97% compared with ST-deviation analysis alone (both p<0.001). MACE-free survival was 90%, 80% and 42% in patients in the 'rule-out', intermediate and 'rule-in' groups ( p<0.001). After adjustment for age, gender, ST-deviations and clinical post-test probability of ischaemia, high-frequency QRS remained an independent predictor for the occurrence of MACEs. CONCLUSION: The use of high-frequency QRS analysis in addition to ST-deviation analysis improves the diagnostic accuracy during exercise stress testing and adds independent prognostic information.

9.
Cardiol Rev ; 27(6): 267-273, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30985328

RESUMO

Myocardial injury after noncardiac surgery (MINS) is a common postoperative complication associated with adverse cardiovascular outcomes. The purpose of this systematic review was to determine the incidence, clinical features, pathogenesis, management, and outcomes of MINS. We searched PubMed, Embase, Central and Web of Science databases for studies reporting the incidence, clinical features, and prognosis of MINS. Data analysis was performed with a mixed-methods approach, with quantitative analysis of meta-analytic methods for incidence, management, and outcomes, and a qualitative synthesis of the literature to determine associated preoperative factors and MINS pathogenesis. A total of 195 studies met study inclusion criteria. Among 169 studies reporting outcomes of 530,867 surgeries, the pooled incidence of MINS was 17.9% [95% confidence interval (CI), 16.2-19.6%]. Patients with MINS were older, more frequently men, and more likely to have cardiovascular risk factors and known coronary artery disease. Postoperative mortality was higher among patients with MINS than those without MINS, both in-hospital (8.1%, 95% CI, 4.4-12.7% vs 0.4%, 95% CI, 0.2-0.7%; relative risk 8.3, 95% CI, 4.2-16.6, P < 0.001) and at 1-year after surgery (20.6%, 95% CI, 15.9-25.7% vs 5.1%, 95% CI, 3.2-7.4%; relative risk 4.1, 95% CI, 3.0-5.6, P < 0.001). Few studies reported mechanisms of MINS or the medical treatment provided. In conclusion, MINS occurs frequently in clinical practice, is most common in patients with cardiovascular disease and its risk factors, and is associated with increased short- and long-term mortality. Additional investigation is needed to define strategies to prevent MINS and treat patients with this diagnosis.

11.
Clin Chem ; 65(7): 893-904, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30988172

RESUMO

BACKGROUND: The aim of this study was to validate the clinical performance of the Beckman Access high-sensitivity cardiac troponin I (hs-cTnI) assay. METHODS: We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists with all clinical information including cardiac imaging twice: first, using serial hs-cTnT (Elecsys, primary analysis), and second, using hs-cTnI (Architect, secondary analysis) measurements in addition to the clinically used hs-cTn. hs-cTnI Access was measured at presentation and at 1 h. The primary objective was a direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI Access vs the hs-cTnT Elecsys and hs-cTnI Architect assays. Secondary objectives included the derivation and validation of an hs-cTnI Access-specific 0/1-h algorithm. RESULTS: AMI was the adjudicated final diagnosis in 243 of 1579 (15.4%) patients. The AUC at presentation for hs-cTnI Access was 0.95 (95% CI, 0.94-0.96), higher than hs-cTnI Architect [0.92 (95% CI, 0.91-0.94; P < 0.001)] and comparable to hs-cTnT Elecsys [0.94 (95% CI, 0.93-0.95; P = 0.12)]. Applying the derived hs-cTnI Access 0/1-h algorithm (derivation cohort n = 686) to the validation cohort (n = 680), 60% of patients were ruled out [sensitivity, 98.9% (95% CI, 94.3-99.8)], and 15% of patients were ruled in [specificity, 95.9% (95% CI, 94.0-97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 100% at 30 days. Findings were confirmed in the secondary analyses by the adjudication including serial measurements of Architect hs-cTnI. CONCLUSIONS: Diagnostic accuracy and clinical utility of the Beckman hs-cTnI Access assay are very high and at least comparable to Roche hs-cTnT and Abbott hs-cTnI assays. ClinicalTrials.gov Identifier: NCT00470587.

12.
Int J Cardiol ; 286: 104-110, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30853296

RESUMO

BACKGROUND: Relative hypochromia of erythrocytes defined as a reduced mean corpuscular hemoglobin concentration (MCHC) is a surrogate of iron deficiency. We aimed to evaluate the prevalence and prognostic impact of relative hypochromia in acute heart failure (AHF). METHODS: We prospectively characterized 1574 patients presenting with an adjudicated diagnosis of AHF to the emergency department. Relative hypochromia was defined as a MCHC ≤330 g/l and determined at presentation. The presence of AHF was adjudicated by two independent cardiologists. All-cause mortality and AHF-rehospitalization were the primary prognostic end-points. RESULTS: Overall, 455 (29%) AHF patients had relative hypochromia. Patients with relative hypochromia had higher hemodynamic cardiac stress as quantified by NT-proBNP concentrations (p < 0.001), more extensive cardiomyocyte injury as quantified by high-sensitive cardiac troponin T (hs-cTnT) concentrations (p < 0.001), and lower estimated glomerular filtration rate (eGFR; p < 0.001) as compared to AHF patients without hypochromia. Cumulative incidences for all-cause mortality and AHF-rehospitalization at 720-days were 50% and 55% in patients with relative hypochromia as compared to 33% and 39% in patients without hypochromia, respectively (both p < 0.0001). The association between relative hypochromia and increased mortality (HR 1.7, 95% CI 1.4-2-0) persisted after adjusting for anemia (HR 1.5, 95% CI 1.3-1.8), and after adjusting for hemodynamic cardiac stress (HR 1.46, 95% CI 1.21-1.76) and eGFR (HR 1.5, 95% CI 1.3-1.8, p < 0.001). CONCLUSIONS: Relative hypochromia is common and a strong and independent predictor of increased mortality in AHF. Given the direct link to diagnostic (endoscopy) and therapeutic interventions to treat functional iron deficiency, relative hypochromia deserves increased attention as an inexpensive and universally available biomarker.

13.
Eur J Clin Invest ; : e13112, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30925205

RESUMO

BACKGROUND: The phenomenon of exercise-induced left ventricular dysfunction (LVD) is incompletely understood. Better understanding of its prevalence and determinants might help to address the current potential oversimplification of the relation between physical activity and cardiac health in patients with coronary artery disease (CAD). METHODS: We prospectively assessed the prevalence and determinants of exercise-induced LVD in patients with stable CAD and normal LV function at rest undergoing bicycle rest/stress myocardial perfusion imaging single-photon emission computed tomography (MPI-SPECT). Exercise-induced LVD was defined as a relevant (5% or more) drop in left ventricular ejection fraction after maximal exercise. High-sensitivity cardiac troponin I/T (Hs-cTnI/T) and N-terminal probrain natriuretic peptide (NT-proBNP) concentrations were measured before exercise to quantify cardiomyocyte injury and hemodynamic cardiac stress, respectively. RESULTS: Among 317 patients, exercise-induced LVD was present in 83 (26%) patients. Exercise-induced LVD was associated with the extent of exercise-inducible myocardial ischaemia as well as transient ischaemic dilatation. Still, 43% of patients developing exercise-induced LVD did not have functionally relevant CAD. Neither baseline characteristics, nor the quantification of the extent of cardiomyocyte injury and hemodynamic cardiac stress using hs-cTnI/T and NT-proBNP concentrations, respectively, allowed predicting exercise-induced LVD. CONCLUSION: One out of four patients with stable CAD develops exercise-induced LVD after bicycle exercise test. While the extent of exercise-inducible myocardial ischaemia is a predictor, other still unrecognized mechanisms also seem to play a major role, as nearly half of all patients with exercise-induced LVD do not have functionally relevant CAD.

14.
Circulation ; 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30798615

RESUMO

BACKGROUND: The utility of B-type Natriuretic Peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin (hs-cTn) concentrations for diagnosis and risk-stratification of syncope is incompletely understood. METHODS: We evaluated the diagnostic and prognostic accuracy of BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations, alone and against the ones of clinical assessments, in patients >45years presenting with syncope to the emergency department (ED) in a prospective diagnostic multicenter study. BNP, NT-proBNP, hs-cTnT and hs-cTnI concentrations were measured in a blinded fashion. Cardiac syncope, as adjudicated by two physicians based on all information available including cardiac work-up and 1-year follow-up, was the diagnostic endpoint. The EGSYS, a syncope-specific diagnostic score, served as the diagnostic comparator. Death and MACE at 30 and 720 days were the prognostic endpoints. MACE were defined as death, cardiopulmonary resuscitation, life-threatening arrhythmia, implantation of pacemaker/implantable cardioverter defibrillator, acute myocardial infarction, pulmonary embolism, stroke/transient ischemic attack, intracranial bleeding or valvular surgery. The ROSE, OESIL, San Fransisco Syncope Rule (SFSR) and Canadian Syncope Risk Score (CSRS) served as the prognostic comparators. RESULTS: Among 1538 patients eligible for diagnostic assessment, cardiac syncope was the adjudicated diagnosis in 234 patients (15.2%). BNP, NT-proBNP, hs-cTnT, and hs-cTnI were significantly higher in cardiac syncope vs. other causes (p<0.01). The diagnostic accuracy for cardiac syncope, as quantified by the area under the curve (AUC), was 0.77-0.78 (95% confidence interval (CI) 0.74-0.81) for all four biomarkers, and superior to the one of EGSYS (AUC 0.68 [95%-CI 0.65-0.71], p<0.001). Combining BNP/NT-proBNP with hs-cTnT/hs-cTnI further improved diagnostic accuracy to an AUC of 0.81 (p<0.01). BNP, NT-proBNP, hs-cTnT, and hs-cTnI cut-offs, achieving pre-defined thresholds for sensitivity and specificity (95%), allowed for rule-in or rule-out of ~30% of all patients. A total of 450 MACE occurred during follow-up. The prognostic accuracy of BNP, NT-proBNP, hs-cTnI, and hs-cTnT for MACE was moderate-to-good (AUC 0.75-0.79), superior to ROSE, OESIL and SFSR, and inferior to the CSRS. CONCLUSIONS: BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations provide useful diagnostic and prognostic information in ED patients with syncope. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov Unique Identifier: NCT01548352.

15.
Ann Intern Med ; 170(4): 248-256, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30690646

RESUMO

Background: The MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF) score was developed to predict 30-day mortality in patients presenting with acute heart failure (AHF) to emergency departments (EDs) in Spain. Whether it performs well in other countries is unknown. Objective: To externally validate the MEESSI-AHF score in another country. Design: Prospective cohort study. (ClinicalTrials.gov: NCT01831115). Setting: Multicenter recruitment of dyspneic patients presenting to the ED. Participants: The external validation cohort included 1572 patients with AHF. Measurements: Calculation of the MEESSI-AHF score using an established model containing 12 independent risk factors. Results: Among 1572 patients with adjudicated AHF, 1247 had complete data that allowed calculation of the MEESSI-AHF score. Of these, 102 (8.2%) died within 30 days. The score predicted 30-day mortality with excellent discrimination (c-statistic, 0.80). Assessment of cumulative mortality showed a steep gradient in 30-day mortality over 6 predefined risk groups (0 patients in the lowest-risk group vs. 35 [28.5%] in the highest-risk group). Risk was overestimated in the high-risk groups, resulting in a Hosmer-Lemeshow P value of 0.022. However, after adjustment of the intercept, the model showed good concordance between predicted risks and observed outcomes (P = 0.23). Findings were confirmed in sensitivity analyses that used multiple imputation for missing values in the overall cohort of 1572 patients. Limitations: External validation was done using a reduced model. Findings are specific to patients with AHF who present to the ED and are clinically stable enough to provide informed consent. Performance in patients with terminal kidney failure who are receiving long-term dialysis cannot be commented on. Conclusion: External validation of the MEESSI-AHF risk score showed excellent discrimination. Recalibration may be needed when the score is introduced to new populations. Primary Funding Source: The European Union, the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel, and University Hospital Basel.

16.
Clin Chem ; 65(3): 437-450, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30626633

RESUMO

BACKGROUND: We desired to determine cardiac troponin (cTn) concentrations necessary to achieve a positive predictive value (PPV) of ≥75% for acute myocardial infarction (AMI) to justify immediate admission of patients to a monitored unit and, in general, early coronary angiography. METHODS: In a prospective multicenter diagnostic study enrolling patients presenting to the emergency department with symptoms suggestive of AMI, final diagnoses were adjudicated by 2 independent cardiologists based on clinical information including cardiac imaging. cTn concentrations were measured using 5 different sensitive and high-sensitivity cTn (hs-cTn) assays in a blinded fashion at presentation and serially thereafter. The diagnostic end point was PPV for rule-in of AMI of initial cTn concentrations alone and in combination with early changes. RESULTS: Among 3828 patients, 616 (16%) had an AMI. At presentation, 7% to 14% of patients had cTnT/I concentrations associated with a PPV of ≥75%. Adding absolute or relative changes did not significantly further increase the PPV. PPVs increased from 46.5% (95% CI, 43.6-49.4) for hs-cTnT at presentation >14 ng/L to 78.9% (95% CI, 74.7-82.5) for >52 ng/L (P < 0.001), whereas PPVs in higher hs-cTnT strata remained largely unchanged [e.g., 82.4% (95% CI, 77.5-86.7) for >80 ng/L vs 83.9% (95% CI, 76.0-90.1) for >200 ng/L (P = 0.72)]. The addition of early changes in hs-cTnT further increased the PPV up to 60 ng/L, but not for higher concentrations. CONCLUSIONS: Serial sampling does not seem necessary for predicting AMI and concurrent decision-making in about 10% of patients, as it only marginally increases the PPV for AMI and not in a statistically or clinically significant way. CLINICALTRIALSGOV IDENTIFIER: NCT00470587.

17.
Int J Cardiol ; 283: 41-47, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30545622

RESUMO

BACKGROUND: The clinical availability of high-sensitivity cardiac troponin (hs-cTn) has enabled the development of several innovative strategies for the rapid rule-out of acute myocardial infarction (AMI). Due to the lack of direct comparisons, selection of the best strategy for clinical practice is challenging. METHODS: In a prospective international multicenter diagnostic study enrolling 3696 patients presenting with suspected AMI to the emergency department, we compared the safety and efficacy of 14 different hs-cTn-based strategies: hs-cTn concentrations below the limit of detection (LoD), dual-marker combining hs-cTn with copeptin, ESC 0 h/1 h-algorithm, 0 h/2 h-algorithm, 2 h-ADP-algorithm, NICE-algorithm, and ESC 0 h/3 h-algorithm, each using either hs-cTnT or hs-cTnI. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available clinical information including cardiac imaging and serial hs-cTn concentrations. RESULTS: AMI was the final diagnosis in 16% of patients. Using hs-cTnT, safety quantified by the negative predictive value (NPV) and sensitivity was very high (99.8-100% and 99.5-100%) and comparable for all strategies, except the dual-marker approach (NPV 98.7%, sensitivity 96.7%). Similarly, using hs-cTnI, safety quantified by the NPV and sensitivity was very high (99.7-100% and 98.9-100%) and comparable for all strategies, except the dual-marker approach (NPV 96.9%, sensitivity 90.4%) and the NICE-algorithm (NPV 99.1%, sensitivity 94.7%). Efficacy, quantified by the percentage of patients eligible for rule-out, differed markedly, and was lowest for LoD-algorithm (15.7-26.8%). CONCLUSION: All rapid rule-out algorithms, except the dual-marker strategy and the NICE-algorithm using hs-cTnI, favorably combine safety and efficacy, and can be considered for routine clinical practice. CLINICAL TRIAL REGISTRATION: NCT00470587, http://clinicaltrials.gov/show/NCT00470587.

18.
Heart ; 105(11): 826-833, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30541757

RESUMO

OBJECTIVE: Recently, daytime variation in perioperative myocardial injury (PMI) has been observed in patients undergoing cardiac surgery. We aim at investigating whether daytime variation also occurs in patients undergoing non-cardiac surgery. METHODS: In a prospective diagnostic study, we evaluated the presence of daytime variation in PMI in patients at increased cardiovascular risk undergoing non-cardiac surgery, as well as its possible impact on the incidence of acute myocardial infarction (AMI), and death during 1-year follow-up in a propensity score-matched cohort. PMI was defined as an absolute increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration of ≥14 ng/L from preoperative to postoperative measurements. RESULTS: Of 1641 patients, propensity score matching defined 630 with similar baseline characteristics, half undergoing non-cardiac surgery in the morning (starting from 8:00 to 11:00) and half in the afternoon (starting from 14:00 to 17:00). There was no difference in PMI incidence between both groups (morning: 50, 15.8% (95% CI 12.3 to 20.3); afternoon: 52, 16.4% (95% CI 12.7 to 20.9), p=0.94), nor if analysing hs-cTnT release as a quantitative variable (median morning group: 3 ng/L (95% CI 1 to 7 ng/L); median afternoon group: 2 ng/L (95% CI 0 to 7 ng/L; p=0.16). During 1-year follow-up, the incidence of AMI was 1.2% (95% CI 0.4% to 3.2%) among morning surgeries versus 4.1% (95% CI 2.3% to 6.9%) among the afternoon surgeries (corrected HR for afternoon surgery 3.44, bootstrapped 95% CI 1.33 to 10.49, p log-rank=0.03), whereas no difference in mortality emerged (p=0.70). CONCLUSIONS: Although there is no daytime variation in PMI in patients undergoing non-cardiac surgery, the incidence of AMI during follow-up is increased in afternoon surgeries and requires further study. CLINICAL TRIAL REGISTRATION: NCT02573532;Results.

19.
Int J Cardiol ; 275: 20-25, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30340850

RESUMO

BACKGROUND: Inflammation plays a major role in the pathogenesis of coronary artery disease (CAD). METHODS: We hypothesized, that quantifying inflammation by measuring circulating interleukin-6 concentrations help in the diagnosis and/or prediction of functionally relevant CAD. Among consecutive patients with symptoms suggestive of CAD, functionally relevant CAD was adjudicated in two domains: first, diagnosis according to myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography; second, cardiovascular death and all-cause death during 2-years follow-up. Adjudication was done blinded to the interleukin-6 concentrations. RESULTS: Among 1553 patients, symptoms were adjudicated to be causally related to CAD in 43% (665/1553). Interleukin-6 concentrations were higher in patients with functionally relevant CAD as compared to those without (1.56 pg/mL versus 1.30 pg/mL, p < 0.001), but overall had only low-to-modest diagnostic accuracy (area under the curve [AUC]: 0.57, 95%CI 0.55-0.61) and were no independent predictor of functionally relevant CAD after multivariable adjustment (p = 0.068). Interleukin-6 concentrations had moderate-to-high accuracy in the prediction of cardiovascular death (AUC 0.75, 95%CI 0.69-0.82) and all-cause death (AUC 0.72, 95%CI 0.66-0.78) at 2-years, and remained a significant predictor after multivariable adjustment (p < 0.001). Compared to patients with interleukin-6 concentrations below the median (1.41 pg/mL), patients with concentrations above the median had a significantly higher cumulative incidence of cardiovascular death (1% vs. 4%, log-rank p < 0.001) and all-cause death (2% vs. 8%, log-rank p < 0.001) at 2 years. CONCLUSION: Interleukin-6 concentrations are strong and independent predictors of cardiovascular death and all-cause death.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Diagnóstico Precoce , Interleucina-6/sangue , Idoso , Biomarcadores/sangue , Causas de Morte/tendências , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Teste de Esforço , Feminino , Seguimentos , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Taxa de Sobrevida/tendências , Suíça/epidemiologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos
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