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Publisher: Elsevier BV
Date: 07-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-12-2017
Abstract: The early detection of cardiac syncope is challenging. We aimed to evaluate the diagnostic value of 4 novel prohormones, quantifying different neurohumoral pathways, possibly involved in the pathophysiological features of cardiac syncope: midregional–pro‐A‐type natriuretic peptide ( MR pro ANP ), C‐terminal proendothelin 1, copeptin, and midregional‐proadrenomedullin. We prospectively enrolled unselected patients presenting with syncope to the emergency department ( ED ) in a diagnostic multicenter study. ED probability of cardiac syncope was quantified by the treating ED physician using a visual analogue scale. Prohormones were measured in a blinded manner. Two independent cardiologists adjudicated the final diagnosis on the basis of all clinical information, including 1‐year follow‐up. Among 689 patients, cardiac syncope was the adjudicated final diagnosis in 125 (18%). Plasma concentrations of MR pro ANP , C‐terminal proendothelin 1, copeptin, and midregional‐proadrenomedullin were all significantly higher in patients with cardiac syncope compared with patients with other causes ( P .001). The diagnostic accuracies for cardiac syncope, as quantified by the area under the curve, were 0.80 (95% confidence interval [CI], 0.76–0.84), 0.69 (95% CI , 0.64–0.74), 0.58 (95% CI , 0.52–0.63), and 0.68 (95% CI , 0.63–0.73), respectively. In conjunction with the ED probability (0.86 95% CI , 0.82–0.90), MR pro ANP, but not the other prohormone, improved the area under the curve to 0.90 (95% CI, 0.87–0.93), which was significantly higher than for the ED probability alone ( P =0.003). An algorithm to rule out cardiac syncope combining an MR pro ANP level of pmol/L and an ED probability of % had a sensitivity and a negative predictive value of 99%. The use of MR pro ANP significantly improves the early detection of cardiac syncope among unselected patients presenting to the ED with syncope. URL : www.clinicaltrials.gov . Unique identifier: NCT 01548352.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-09-2018
DOI: 10.1161/CIRCULATIONAHA.117.032003
Abstract: Combining 2 signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some in idual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high-sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of acute myocardial infarction. The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio, and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected acute myocardial infarction. The optimal rule-out and rule-in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule-out was compared with the European Society of Cardiology 0/1 and 0/3 hour algorithms. Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the in idual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the European Society of Cardiology 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule-out criteria after the baseline blood s ling was limited (6% to 24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng 2 /L 2 ) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34% to 41% in the original (sum: negative predictive value [NPV] 100% [95% confidence interval (CI), 99.5% to 100%] product: NPV 100% [95% CI, 99.5% to 100%]) and in the validation cohort (sum: NPV 99.6% [95% CI, 99.0–99.9%] product: NPV 99.4% [95% CI, 98.8–99.8%]). The use of a combination algorithm (hs-cTnI ng/L and hs-cTnT ng/L) showed comparable results for rule-out (40% to 43% ruled out NPV original cohort 99.9% [95% CI, 99.2–100%] NPV validation cohort 99.5% [95% CI, 98.9–99.8%]) and rule-in (positive predictive value [PPV] original cohort 74.4% [95% Cl, 69.6–78.8%] PPV validation cohort 84.0% [95% Cl, 79.7–87.6%]). New strategies combining hs-cTnI and hs-cTnT concentrations may significantly increase the number of patients eligible for very early and safe rule-out, but do not seem helpful for the rule-in of acute myocardial infarction. URL (APACE): www.clinicaltrial.gov . Unique identifier: NCT00470587. URL (ADAPT): www.anzctr.org.au . Unique identifier: ACTRN12611001069943.
Publisher: BMJ
Date: 29-05-2019
DOI: 10.1136/HEARTJNL-2018-314673
Abstract: 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. 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. 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%). 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. APACE: NCT00470587 ADAPT: ACTRN12611001069943 TRAPID-AMI: RD001107 Results.
Publisher: Frontiers Media SA
Date: 04-10-2018
Publisher: Wiley
Date: 24-04-2019
DOI: 10.1002/EJHF.1471
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-10-2017
DOI: 10.1161/CIRCULATIONAHA.117.028084
Abstract: Cardiac myosin-binding protein C (cMyC) is a cardiac-restricted protein that is more abundant than cardiac troponins (cTn) and is released more rapidly after acute myocardial infarction (AMI). We evaluated cMyC as an adjunct or alternative to cTn in the early diagnosis of AMI. Unselected patients (N=1954) presenting to the emergency department with symptoms suggestive of AMI, concentrations of cMyC, and high-sensitivity (hs) and standard-sensitivity cTn were measured at presentation. The final diagnosis of AMI was independently adjudicated using all available clinical and biochemical information without knowledge of cMyC. The prognostic end point was long-term mortality. Final diagnosis was AMI in 340 patients (17%). Concentrations of cMyC at presentation were significantly higher in those with versus without AMI (median, 237 ng/L versus 13 ng/L, P .001). Discriminatory power for AMI, as quantified by the area under the receiver-operating characteristic curve (AUC), was comparable for cMyC (AUC, 0.924), hs-cTnT (AUC, 0.927), and hs-cTnI (AUC, 0.922) and superior to cTnI measured by a contemporary sensitivity assay (AUC, 0.909). The combination of cMyC with hs-cTnT or standard-sensitivity cTnI (but not hs-cTnI) led to an increase in AUC to 0.931 ( P .0001) and 0.926 ( P =0.003), respectively. Use of cMyC more accurately classified patients with a single blood test into rule-out or rule-in categories: Net Reclassification Improvement +0.149 versus hs-cTnT, +0.235 versus hs-cTnI ( P .001). In early presenters (chest pain h), the improvement in rule-in/rule-out classification with cMyC was larger compared with hs-cTnT (Net Reclassification Improvement +0.256) and hs-cTnI (Net Reclassification Improvement +0.308 both P .001). Comparing the C statistics, cMyC was superior to hs-cTnI and standard sensitivity cTnI ( P .05 for both) and similar to hs-cTnT at predicting death at 3 years. cMyC at presentation provides discriminatory power comparable to hs-cTnT and hs-cTnI in the diagnosis of AMI and may perform favorably in patients presenting early after symptom onset. URL: www.clinicaltrials.gov . Unique identifier: NCT00470587.
Publisher: Wiley
Date: 04-01-2018
DOI: 10.1002/EJHF.1111
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.JACC.2018.05.040
Abstract: The safety of the European Society of Cardiology (ESC) 0/1-h algorithm for rapid rule-out and rule-in of non-ST-segment elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac troponin (hs-cTn) has been questioned. This study aimed to validate the diagnostic performance of the 0/1-h algorithm in a large multicenter study. The authors prospectively enrolled unselected patients in 6 countries presenting to the emergency department with symptoms suggestive of NSTEMI. Final diagnosis was centrally adjudicated by 2 independent cardiologists. Hs-cTnT and hs-cTnI blood concentrations were measured at presentation and after 1 h. Safety of rule-out was quantified by the negative predictive value (NPV) for NSTEMI, accuracy of rule-in by the positive predictive value (PPV), and overall efficacy by the proportion of patients triaged towards rule-out or rule-in within 1 h. Prevalence of NSTEMI was 17%. Among 4,368 patients with serial hs-cTnT measurements available, safety of rule-out (NPV 99.8%, 2,488 of 2,493), accuracy of rule-in (PPV 74.5%, 572 of 768), and overall efficacy were high by assigning three-fourths of patients either to rule-out (57%, 2,493 to 4,368) or rule-in (18%, 768 to 4,368). Similarly, among 3,500 patients with serial hs-cTnI measurements, safety of rule-out (NPV 99.7%, 1,528 of 1,533), accuracy of rule-in (PPV 62.3%, 498 of 800), and overall efficacy were high by assigning more than two-thirds of patients either to rule-out (44%, 1,533 of 3,500) or rule-in (23%, 800 of 3,500). Excellent safety was confirmed in multiple subgroup analyses including patients presenting early (≤3 h) after chest pain onset. The ESC 0/1-h algorithm using hs-cTnT and hs-cTnI is very safe and effective in triaging patients with suspected NSTEMI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] NCT00470587 and Biomarkers in Acute Cardiac Care [BACC] NCT02355457).
Publisher: Oxford University Press (OUP)
Date: 03-2019
DOI: 10.1373/CLINCHEM.2018.294124
Abstract: 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. 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. 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 & ng/L to 78.9% (95% CI, 74.7–82.5) for & 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 & ng/L vs 83.9% (95% CI, 76.0–90.1) for & 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. Serial s ling 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. NCT00470587.
Publisher: Oxford University Press (OUP)
Date: 06-08-2022
Abstract: The aim of this TeleCheck-AF sub-analysis was to evaluate motivation and adherence to on-demand heart rate/rhythm monitoring app in patients with atrial fibrillation (AF). Patients were instructed to perform 60 s app-based heart rate/rhythm recordings 3 times daily and in case of symptoms for 7 consecutive days prior to teleconsultation. Motivation was defined as number of days in which the expected number of measurements (≥3/day) were performed per number of days over the entire prescription period. Adherence was defined as number of performed measurements per number of expected measurements over the entire prescription period.Data from 990 consecutive patients with diagnosed AF [median age 64 (57-71) years, 39% female] from 10 centres were analyzed. Patients with both optimal motivation (100%) and adherence (≥100%) constituted 28% of the study population and had a lower percentage of recordings in sinus rhythm [90 (53-100%) vs. 100 (64-100%), P < 0.001] compared with others. Older age and absence of diabetes were predictors of both optimal motivation and adherence [odds ratio (OR) 1.02, 95% coincidence interval (95% CI): 1.01-1.04, P < 0.001 and OR: 0.49, 95% CI: 0.28-0.86, P = 0.013, respectively]. Patients with 100% motivation also had ≥100% adherence. Independent predictors for optimal adherence alone were older age (OR: 1.02, 95% CI: 1.00-1.04, P = 0.014), female sex (OR: 1.70, 95% CI: 1.29-2.23, P < 0.001), previous AF ablation (OR: 1.35, 95% CI: 1.03-1.07, P = 0.028). In the TeleCheck-AF project, more than one-fourth of patients had optimal motivation and adherence to app-based heart rate/rhythm monitoring. Older age and absence of diabetes were predictors of optimal motivation/adherence.
Publisher: Public Library of Science (PLoS)
Date: 06-04-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-06-2018
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.IJCARD.2018.09.040
Abstract: The value of the 12-lead ECG in the diagnosis of non-ST-elevation myocardial infarction (NSTEMI) is limited due to insufficient sensitivity and specificity of standard ECG criteria. The QRS-T angle reflects depolarization-repolarization heterogeneity and might assist in detecting patients with a NSTEMI (diagnosis) as well as predicting patients with an increased mortality risk (prognosis). We prospectively enrolled 2705 consecutive patients with symptoms suggestive of NSTEMI. The QRS-T angle was automatically derived from the standard 10 s 12-lead ECG recorded at presentation to the ED. Patients were followed up for all-cause mortality for 2 years. NSTEMI was the final diagnosis in 15% (n = 412) of patients. QRS-T angles were significantly greater in patients with NSTEMI compared to those without (p < 0.001). The use of the QRS-T angle in addition to standard ECG criteria indicative of ischemia improved the diagnostic accuracy for NSTEMI as quantified by the area under the ROC curve from 0.68 to 0.72 (p < 0.001). An algorithm for the combined use of standard ECG criteria and the QRS-T angle improved the sensitivity of the ECG for NSTEMI from 45% to 78% and the specificity from 86% to 91% (p < 0.001 for both comparisons). The 2-year survival rates were 98%, 97% and 87% according to QRS-T angle tertiles (p < 0.001). In patients with suspected NSTEMI, the QRS-T angle derived from the standard 12-lead ECG provides incremental diagnostic accuracy on top of standard ECG criteria indicative of ischemia, and independently predicts all-cause mortality during 2 years of follow-up.
Publisher: Oxford University Press (OUP)
Date: 29-08-2018
Abstract: We aimed to evaluate the impact of age on the performance of the European Society of Cardiology (ESC) 0/1h-algorithms and to derive and externally validate alternative cut-offs specific to older patients. We prospectively enrolled patients presenting to the emergency department (ED) with symptoms suggestive of acute myocardial infarction in three large diagnostic studies. Final diagnoses were adjudicated by two independent cardiologists. High-sensitivity cardiac troponin (hs-cTn) T and I concentrations were measured at presentation and after 1 h. Patients were stratified according to age [<55 years (young), ≥55 to <70 years (middle-age), ≥70 years (old)]. Rule-out safety of the ESC hs-cTnT 0/1h-algorithm was very high in all age-strata: sensitivity 100% [95% confidence interval (95% CI) 94.9-100] in young, 99.3% (95% CI 96.0-99.9) in middle-age, and 99.3% (95% CI 97.5-99.8) in old patients. Accuracy of rule-in decreased with age: specificity 97.0% (95% CI 95.8-97.9) in young, 96.1% (95% CI 94.5-97.2) in middle-age, and 92.7% (95% CI 90.7-94.3) in older patients. Triage efficacy decreased with increasing age (young 93%, middle-age 80%, old 55%, P < 0.001). Similar results were found for the ESC hs-cTnT 0/1h-algorithm. Alternative, slightly higher cut-off concentrations optimized for older patients maintained very high safety of rule-out, increased specificity of rule-in (P < 0.01), reduced overall efficacy for hs-cTnT (P < 0.01), while maintaining efficacy for hs-cTnI. Findings were confirmed in two validation cohorts (n = 2767). While safety of the ESC 0/1h-algorithms remained very high, increasing age significantly reduced overall efficacy and the accuracy of rule-in. Alternative slightly higher cut-off concentrations may be considered for older patients, particularly if using hs-cTnI. t2/show/NCT00470587, number NCT00470587 and NCT02355457 (BACC).
Publisher: Oxford University Press (OUP)
Date: 07-2017
DOI: 10.1373/CLINCHEM.2016.268359
Abstract: We compared 2 high-sensitivity cardiac troponin (hs-cTn)-based 2-h strategies in patients presenting with suspected acute myocardial infarction (AMI) to the emergency department (ED): the 2-h accelerated diagnostic protocol (2h-ADP) combining hs-cTn, electrocardiogram, and a risk score, and the 2-h algorithm exclusively based on hs-cTn concentrations and their absolute changes. Analyses were performed in 2 independent diagnostic cohorts [European Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) study, Australian–New Zealand 2-h Accelerated Diagnostic Protocol to Assess patients with chest Pain symptoms using contemporary Troponins as the only biomarker (ADAPT) study] employing hs-cTnT (Elecsys) and hs-cTnI (Architect). The final diagnosis was adjudicated by 2 independent cardiologists. AMI was the final diagnosis in 16.5% (95% CI, 14.6%–18.6%) of the 1372 patients in APACE, and 12.6% (95% CI, 10.7%–14.7%) of 1153 patients in ADAPT. The negative predictive value (NPV) and sensitivity for AMI were very high and comparable with both strategies using either hs-cTnT or hs-cTnI in both cohorts (all statistical comparisons nonsignificant). The percentage of patients triaged toward rule-out was significantly lower with the 2h-ADP (36%–43%) vs the 2-h algorithm (55%–68%) with both assays and in both cohorts (P & 0.001). The sensitivity of the 2h-ADP was higher for 30-day major adverse cardiovascular events. Both algorithms provided very high and comparable safety as quantified by the NPV and sensitivity for AMI and major adverse cardiac events (MACE) at 30 days in patients triaged toward rule-out, although sensitivity for MACE at 30 days was lower with both algorithms in cohort 2. Although the 2-h algorithm was more efficacious, not all patients ruled out for AMI by this algorithm were appropriate candidates for early discharge. The 2h-ADP seems superior in the selection of patients for early discharge from the ED. APACE: how/NCT00470587 ADAPT: Australia-New Zealand Clinical Trials Registry ACTRN12611001069943
Publisher: VM Media SP. zo.o VM Group SK
Date: 30-10-2018
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.IJCARD.2019.02.060
Abstract: 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). 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. 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). 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.
Publisher: American Medical Association (AMA)
Date: 11-2016
DOI: 10.1001/JAMACARDIO.2016.2882
Abstract: It is currently unknown whether the uniform (universal clinical practice for more than 2 decades) or 2 sex-specific cutoff levels are preferable when using high-sensitivity cardiac troponin T (hs-cTnT) levels in the diagnosis of acute myocardial infarction (AMI). To improve the management of suspected AMI in women by exploring sex-specific vs uniform cutoff levels for hs-cTnT. In an ongoing prospective, diagnostic, multicenter study conducted at 9 emergency departments, the present study evaluated patients enrolled from April 21, 2006, through June 5, 2013. The participants included 2734 adults presenting with suspected AMI. Duration of follow-up was 2 years, and data analysis occurred from June 5 to December 21, 2015. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including measurements of serial hs-cTnT blood concentrations twice: once using the uniform 99th percentile cutoff value level of 14 ng/L and once using sex-specific 99th percentile levels of hs-cTnT (women, 9 ng/L men, 15.5 ng/L). Diagnostic reclassification in women and men using sex-specific vs the uniform cutoff level in the diagnosis of AMI. Of the 2734 participants, 876 women (32%) and 1858 men (68%) were included. Median (interquartile range) age was 68 (55-77) and 59 (48-71) years, respectively. With the use of the uniform cutoff value, 127 women (14.5%) and 345 men (18.6%) received a final diagnosis of AMI. Among these, at emergency department presentation, levels of hs-cTnT were already above the uniform cutoff value in 427 patients (sensitivity, 91.3% [95% CI, 85%-95.6%] in women vs 90.7% [95% CI, 87.1%-93.5% in men] specificity, 79.2% [95% CI, 76.1%-82.1%] in women vs 78.5% [95% CI, 76.4%-80.6%] in men). After readjudication using sex-specific 99th percentile levels, diagnostic reclassification regarding AMI occurred in only 3 patients: 0.11% (95% CI, 0.02-0.32) of all patients and 0.6% (95% CI, 0.13-1.85) of patients with AMI. The diagnosis in 2 women was upgraded from unstable angina to AMI, and the diagnosis in 1 man was downgraded from AMI to unstable angina. These diagnostic results were confirmed when using 2 alternative pairs of uniform and sex-specific cutoff values. The uniform 99th percentile should remain the standard of care when using hs-cTnT levels for the diagnosis of AMI.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-01-2018
DOI: 10.1161/CIRCULATIONAHA.117.028901
Abstract: The European Society of Cardiology recommends a 0/1-hour algorithm for rapid rule-out and rule-in of non–ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin (hs-cTn) concentrations irrespective of renal function. Because patients with renal dysfunction (RD) frequently present with increased hs-cTn concentrations even in the absence of non–ST-segment elevation myocardial infarction, concern has been raised regarding the performance of the 0/1-hour algorithm in RD. In a prospective multicenter diagnostic study enrolling unselected patients presenting with suspected non–ST-segment elevation myocardial infarction to the emergency department, we assessed the diagnostic performance of the European Society of Cardiology 0/1-hour algorithm using hs-cTnT and hs-cTnI in patients with RD, defined as an estimated glomerular filtration rate mL/min/1.73 m 2 , and compared it to patients with normal renal function. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including cardiac imaging. Safety was quantified as sensitivity in the rule-out zone, accuracy as the specificity in the rule-in zone, and efficacy as the proportion of the overall cohort assigned to either rule-out or rule-in based on the 0- and 1-hour s le. Among 3254 patients, RD was present in 487 patients (15%). The prevalence of non–ST-segment elevation myocardial infarction was substantially higher in patients with RD compared with patients with normal renal function (31% versus 13%, P .001). Using hs-cTnT, patients with RD had comparable sensitivity of rule-out (100.0% [95% confidence interval {CI}, 97.6–100.0] versus 99.2% [95% CI, 97.6–99.8] P =0.559), lower specificity of rule-in (88.7% [95% CI, 84.8–91.9] versus 96.5% [95% CI, 95.7–97.2] P .001), and lower overall efficacy (51% versus 81%, P .001), mainly driven by a much lower percentage of patients eligible for rule-out (18% versus 68%, P .001) compared with patients with normal renal function. Using hs-cTnI, patients with RD had comparable sensitivity of rule-out (98.6% [95% CI, 95.0–99.8] versus 98.5% [95% CI, 96.5–99.5] P =1.0), lower specificity of rule-in (84.4% [95% CI, 79.9–88.3] versus 91.7% [95% CI, 90.5–92.9] P .001), and lower overall efficacy (54% versus 76%, P .001 proportion ruled out, 18% versus 58%, P .001) compared with patients with normal renal function. In patients with RD, the safety of the European Society of Cardiology 0/1-hour algorithm is high, but specificity of rule-in and overall efficacy are decreased. Modifications of the rule-in and rule-out thresholds did not improve the safety or overall efficacy of the 0/1-hour algorithm. URL: www.clinicaltrials.gov . Unique identifier: NCT00470587.
Publisher: Oxford University Press (OUP)
Date: 22-08-2018
Abstract: It is unknown whether cardiac syncope, and possibly also other syncope aetiologies exhibit circadian, weekly, seasonal, and temperature-dependent patterns. We prospectively recorded the exact time, date, and outside temperature of syncope of patients >40 years old presenting with syncope to the emergency department in a diagnostic multicentre study. Two independent cardiologists/emergency physicians adjudicated the final diagnosis based on all information becoming available during clinical work-up including 1-year follow-up. Among 1230 patients, the adjudicated aetiology was cardiac in 14.6%, reflex in 39.2%, orthostatic in 25.7%, other non-cardiac in 9.7%, and unknown in 10.8% of patients. All syncope aetiologies occurred much more frequently during the day when compared with the night (P < 0.01). While reflex and orthostatic syncope showed a broad peak of prevalence with 80.9% of these events occurring between 4 am and 4 pm, cardiac syncope showed a narrow peak of prevalence with 70.1% of all events occurring between 8 am and 2 pm. A weekly pattern was present for most syncope aetiologies, with events occurring mainly from Monday to Friday (P < 0.01). Reflex syncope displayed a seasonal rhythm and was more common in winter (P 40 years old display circadian, weekly, seasonal, and temperature-dependent patterns. Unfortunately, these patterns do not allow to reliably differentiate cardiac syncope from other aetiologies.
Publisher: Oxford University Press (OUP)
Date: 12-2020
Abstract: Recent advances in digital electrocardiography technology allow evaluating ST-segment deviations in all 12 leads as quantitative variables and calculating summed ST-segment deviation scores. The diagnostic and prognostic utility of summed ST-segment deviation scores is largely unknown. We aimed to explore the diagnostic and prognostic utility of the conventional and the modified ST-segment deviation score (Better Analysis of ST-segment Elevations and Depressions in a 12- Lead-ECG-Score (BASEL-Score): sum of elevations in the augmented voltage right - lead (aVR) plus absolute, unsigned ST-segment depressions in the remaining leads) in patients presenting with suspected non-ST-segment elevation myocardial infarction. The diagnostic endpoint was non-ST-segment elevation myocardial infarction, adjudicated by two independent cardiologists. Prognostic endpoint was mortality during two-year follow up. Among 1330 patients, non-ST-segment elevation myocardial infarction was present in 200 (15%) patients. Diagnostic accuracy for non-ST-segment elevation myocardial infarction as quantified by the area under the receiver-operating-characteristics curve was significantly higher for the BASEL-Score (0.73 95% confidence interval 0.69–0.77) as compared to the conventional ST-segment deviation score (0.53 95% confidence interval 0.49–0.57, p& .001). The BASEL-Score provided additional independent diagnostic value to dichotomous electrocardiogram variables (ST-segment depression, T-inversion, both p& .001) and to high-sensitivity cardiac troponin (p& .001) as well as clinical judgment at 90 min (p& .001). Similarly, only the BASEL-Score proved to be an independent predictor of two year mortality. The modified ST-segment deviation score BASEL-Score focusing on ST-segment elevation in aVR and ST-segment depressions in the remaining leads provides incremental diagnostic and prognostic information.
Publisher: Wiley
Date: 15-07-2015
DOI: 10.1002/HED.24102
Abstract: This purpose of this meta-analysis study was to identify the most frequent and potentially significant copy number alteration (CNA) in oral carcinogenesis. Seven oral squamous cell carcinoma (OSCC)-related publications, corresponding to 312 s les, were identified for this meta-analysis. The data were analyzed in a 4-step process that included the genome assembly coordination of multiple platforms, assignment of chromosomal position anchors, calling gains and losses, and functional annotation analysis. Gains were more frequent than losses in the entire dataset. High-frequency gains were identified in chromosomes 5p, 14q, 11q, 7p, 17q, 20q, 8q, and 3q, whereas high-frequency losses were identified in chromosomes 3p, 8p, 6p, 18q, and 4q. Ingenuity pathway analysis showed that the top biological function was associated with immortalization of the epithelial cells (p = 1.93E-04). This study has identified multiple recurrent CNAs that are involved in various biological annotations associated with oral carcinogenesis. © 2015 Wiley Periodicals, Inc. Head Neck 38: E783-E797, 2016.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-12-2016
DOI: 10.1161/CIRCRESAHA.116.309792
Abstract: In contrast to cardiomyocyte necrosis, which can be quantified by cardiac troponin, functional cardiomyocyte impairment, including mitochondrial dysfunction, has escaped clinical recognition in acute myocardial infarction (AMI) patients. To investigate the diagnostic accuracy for AMI and prognostic prediction of in-hospital mortality of cytochrome c . We prospectively assessed cytochrome c serum levels at hospital presentation in 2 cohorts: a diagnostic cohort of patients presenting with suspected AMI and a prognostic cohort of definite AMI patients. Diagnostic accuracy for AMI was the primary diagnostic end point, and prognostic prediction of in-hospital mortality was the primary prognostic end point. Serum cytochrome c had no diagnostic utility for AMI (area under the receiver-operating characteristics curve 0.51 95% confidence intervals 0.44–0.58 P =0.76). Among 753 AMI patients in the prognostic cohort, cytochrome c was detectable in 280 (37%) patients. These patients had higher in-hospital mortality than patients with nondetectable cytochrome c (6% versus 1% P .001). This result was mainly driven by the high mortality rate observed in ST-segment–elevation AMI patients with detectable cytochrome c , as compared with those with nondetectable cytochrome c (11% versus 1% P .001). At multivariable analysis, cytochrome c remained a significant independent predictor of in-hospital mortality (odds ratio 3.0 95% confidence interval 1.9–5.7 P .001), even after adjustment for major clinical confounders (odds ratio 4.01 95% confidence interval 1.20–13.38 P =0.02). Cytochrome c serum concentrations do not have diagnostic but substantial prognostic utility in AMI.
Publisher: Oxford University Press (OUP)
Date: 11-2019
DOI: 10.1373/CLINCHEM.2019.305193
Abstract: We aimed to derive and externally validate a 0/2-h algorithm using the high-sensitivity cardiac troponin I (hs-cTnI)-Access assay. We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI) in 2 prospective diagnostic studies using central adjudication. Two independent cardiologists adjudicated the final diagnosis, including all available medical information including cardiac imaging. hs-cTnI-Access concentrations were measured at presentation and after 2 h in a blinded fashion. AMI was the adjudicated final diagnosis in 164 of 1131 (14.5%) patients in the derivation cohort. Rule-out by the hs-cTnI-Access 0/2-h algorithm was defined as 0-h hs-cTnI-Access concentration & ng/L in patients with an onset of chest pain & h (direct rule-out) or a 0-h hs-cTnI-Access concentration & ng/L and an absolute change within 2 h & ng/L in all other patients. Derived thresholds for rule-in were a 0-h hs-cTnI-Access concentration ≥50 ng/L (direct rule-in) or an absolute change within 2 h ≥20 ng/L. In the derivation cohort, these cutoffs ruled out 55% of patients with a negative predictive value (NPV) of 99.8% (95% CI, 99.3–100) and sensitivity of 99.4% (95% CI, 96.5–99.9), and ruled in 30% of patients with a positive predictive value (PPV) of 73% (95% CI, 66.1–79). In the validation cohort, AMI was the adjudicated final diagnosis in 88 of 1280 (6.9%) patients. These cutoffs ruled out 77.9% of patients with an NPV of 99.8% (95% CI, 99.3–100) and sensitivity of 97.7% (95% CI, 92.0–99.7), and ruled in 5.8% of patients with a PPV of 77% (95% CI, 65.8–86) in the validation cohort. Safety and efficacy of the l hs-cTnI-Access 0/2-h algorithm for triage toward rule-out or rule-in of AMI are very high. APACE, NCT00470587 ADAPT, ACTRN1261100106994 IMPACT, ACTRN12611000206921.
Publisher: Oxford University Press (OUP)
Date: 09-2018
DOI: 10.1373/CLINCHEM.2018.286906
Abstract: Clinical performance of the novel high-sensitivity cardiac troponin I (Siemens-hs-cTnI-Centaur) assay is unknown. We aimed to clinically validate the Siemens-hs-cTnI-Centaur assay and develop 0/1-h and 0/2-h algorithms. 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 including all clinical information twice: first, using serial hs-cTnT (Roche-Elecsys, primary analysis) second, using hs-cTnI (Abbott-Architect, secondary analysis) measurements in addition to the clinically applied (hs)-cTn. Siemens-hs-cTnI-Centaur was measured at presentation, 1 h, and 2 h. The primary objective was a direct comparison of diagnostic accuracy, quantified by the area under the ROC curve (AUC), of Siemens-hs-cTnI-Centaur vs the 2 established hs-cTn assays (Roche-hs-cTnT-Elecsys, Abbott-hs-cTnI-Architect). Secondary objectives included the development of Siemens-hs-cTnI-Centaur-specific 0/1-h and 0/2-h algorithms. AMI was the final diagnosis in 318 of 1755 (18%) patients (using Roche-hs-cTnT-Elecsys for adjudication). The AUC at presentation for Siemens-hs-cTnI-Centaur was 0.94 (95% CI, 0.92–0.96) and comparable with 0.95 (95% CI, 0.93–0.97) for Roche-hs-cTnT-Elecsys and 0.93 (95% CI, 0.90–0.96) for Abbott-hs-cTnI-Architect. Applying the derived Siemens-hs-cTnI-Centaur 0/1-h algorithm to the validation cohort, 46% of patients were ruled out (sensitivity, 99.1% 95% CI, 95.3–100), and 18% of patients were ruled in (specificity, 94.1% 95% CI, 91.8–95.9). The Siemens-hs-cTnI-Centaur 0/2-h algorithm ruled out 55% of patients (sensitivity, 100% 95% CI, 94.1–100), and ruled in 18% of patients (specificity, 96.0% 95% CI, 93.1–97.9). Findings were confirmed in the secondary analyses using serial measurements of Abbott-hs-cTnI-Architect for adjudication. Diagnostic accuracy and clinical utility of the novel Siemens-hs-cTnI-Centaur assay are high and comparable with the established hs-cTn assays. ClinicalTrials.gov Identifier: NCT00470587
Publisher: Springer Science and Business Media LLC
Date: 02-2017
DOI: 10.1007/S00392-016-1075-9
Abstract: The early diagnosis of acute myocardial infarction (AMI) in patients with mild elevations of high-sensitivity cardiac troponin (hs-cTn) is a challenge. It is unclear whether copeptin, a marker of endogenous stress, or 1h-hs-cTn changes are better suited to address this important unmet clinical need. We prospectively enrolled patients presenting with symptoms suggestive of AMI to the emergency department (ED). Two independent cardiologists adjudicated the final diagnosis. Mild hs-cTn elevations were defined as 26.2 ng/L (99th percentile) to 75 ng/L for hs-cTnI, and 14 ng/L (99th percentile) to 50 ng/L (biological-equivalent to 75 ng/L for hs-cTnI) for hs-cTnT. Among 1356 patients, 80 (6%) had mild hs-cTnI elevations at presentation. Within this group, AMI was the final diagnosis in 39 patients (49%). The diagnostic accuracy for the diagnosis of AMI as quantified by the area under the receiver operating characteristic curve (AUC) was 0.51 (95% CI 0.39-0.64) for hs-cTnI at presentation, 0.58 (95% CI 0.45-0.71) for copeptin at presentation, and 0.78 (95% CI 0.68-0.88) for 1h-hs-cTnI changes, which was significantly higher as compared to copeptin (p = 0.02) or hs-cTnI alone (p < 0.001). The additional use of 1h-hs-cTnI changes, but not of copeptin, improved diagnostic accuracy of hs-cTnI at presentation (AUC 0.80, 95% CI 0.70-0.90 p = 0.002 for comparison). Similar findings regarding copeptin and 1h-hs-cTnT/I changes were obtained for mild hs-cTnT elevations. About 6-22% of patients presenting with suggestive AMI to the ED have mild hs-cTnT/I elevations at presentation. In contrast to copeptin, the addition of 1h-hs-cTn changes substantially improves the early diagnosis of AMI.
Publisher: Frontiers Media SA
Date: 19-01-2022
Abstract: The TeleCheck-AF approach is an on-demand mobile health (mHealth) infrastructure incorporating mobile app-based heart rate and rhythm monitoring through teleconsultation. We evaluated feasibility and accuracy of self-reported mHealth-based AF risk factors and CHA 2 DS 2 -VASc-score in atrial fibrillation (AF) patients managed within this approach. Consecutive patients from eight international TeleCheck-AF centers were asked to complete an app-based 10-item questionnaire related to risk factors, associated conditions and CHA 2 DS 2 -VASc-score components. Patient's medical history was retrieved from electronic health records (EHR). Among 994 patients, 954 (96%) patients (38% female, median age 65 years) completed the questionnaire and were included in this analysis. The accuracy of self-reported assessment was highest for pacemaker and anticoagulation treatment and lowest for heart failure and arrhythmias. Patients who knew that AF increases the stroke risk, more often had a 100% or ≥80% correlation between EHR- and app-based results compared to those who did not know (27 vs. 14% or 84 vs. 77%, P = 0.001). Thromboembolic events were more often reported in app (vs. EHR) in all countries, whereas higher self-reported hypertension and anticoagulant treatment were observed in Germany and heart failure in the Netherlands. If the app-based questionnaire alone was used for clinical decision-making on anticoagulation initiation, 26% of patients would have been undertreated and 6.1%—overtreated. Self-reported mHealth-based assessment of AF risk factors is feasible. It shows high accuracy of pacemaker and anticoagulation treatment, nevertheless, displays limited accuracy for some of the CHA 2 DS 2 -VASc-score components. Direct health care professional assessment of risk factors remains indispensable to ensure high quality clinical-decision making.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.IJCARD.2017.01.151
Abstract: The V-index is an ECG marker quantifying spatial heterogeneity of ventricular repolarization. We prospectively assessed the diagnostic and prognostic values of the V-index in patients with suspected non-ST-elevation myocardial infarction (NSTEMI). We prospectively enrolled 497 patients presenting with suspected NSTEMI to the emergency department (ED). Digital 12-lead ECGs of five-minute duration were recorded at presentation. The V-index was automatically calculated in a blinded fashion. Patients with a QRS duration >120ms were ruled out from analysis. The final diagnosis was adjudicated by two independent cardiologists. The prognostic endpoint was all-cause mortality during 24months of follow-up. NSTEMI was the final diagnosis in 14% of patients. V-index levels were higher in patients with AMI compared to other causes of chest pain (median 23ms vs. 18ms, p<0.001). The use of the V-index in addition to conventional ECG-criteria improved the diagnostic accuracy for the diagnosis of NSTEMI as quantified by area under the ROC curve from 0.66 to 0.73 (p=0.001) and the sensitivity of the ECG for AMI from 41% to 86% (p<0.001). Cumulative 24-month mortality rates were 99.4%, 98.4% and 88.3% according to tertiles of the V-index (p<0.001). After adjustment for age and important ECG and clinical parameters, the V-index remained an independent predictor of death. The V-index, an ECG marker quantifying spatial heterogeneity of ventricular repolarization, significantly improves the accuracy and sensitivity of the ECG for the diagnosis of NSTEMI and independently predicts mortality during follow-up.
Publisher: Wiley
Date: 19-10-2016
DOI: 10.1002/EJHF.667
Abstract: Treatment goals in acute heart failure (AHF) are poorly defined. We aimed to characterize further the impact of in-hospital haemoconcentration and worsening renal function (WRF) on short- and long-term mortality. Haematocrit, haemoglobin, total protein, serum creatinine, and albumin levels were measured serially in 1019 prospectively enrolled AHF patients. Haemoconcentration was defined as an increase in at least three of four of the haemoconcentration-defining parameters above admission values at any time during the hospitalization. Patients were ided into early (Day 1-4) and late haemoconcentration (>Day 4). Ninety-day mortality was the primary endpoint. Haemoconcentration occurred in 392 (38.5%) patients, with a similar incidence of the early (44.6%) and late (55.4%) phenotype. Signs of decongestion (reduction in BNP blood concentrations, P = 0.003 weight loss, P = 0.002) were significantly more pronounced in haemoconcentration patients. WRF was more common in haemoconcentration patients (P = 0.04). After adjustment for established risk factors for AHF mortality, including WRF and HF therapy at discharge, haemoconcentration was significantly associated with a reduction in 90-day mortality [hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.37-0.95, P = 0.01]. The beneficial effect of haemoconcentration seemed to be exclusive for late haemoconcentration (late vs. early: adjusted HR 0.41, 95% CI 0.19-0.90, P = 0.03) and persisted in patients with or without WRF. Haemoconcentration represents an inexpensive and easily assessable pathophysiological signal of adequate decongestion in AHF and is associated with lower mortality. WRF in the setting of haemoconcentration does not appear to offset the benefits of haemoconcentration.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-04-2017
DOI: 10.1161/CIRCULATIONAHA.116.025661
Abstract: Four strategies for very early rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I (hs-cTnI) have been identified. It remains unclear which strategy is most attractive for clinical application. We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnI levels were measured at presentation and after 1 hour in a blinded fashion. We directly compared all 4 hs-cTnI–based rule-out strategies: limit of detection (LOD, hs-cTnI ng/L), single cutoff (hs-cTnI ng/L), 1-hour algorithm (hs-cTnI ng/L and 1-hour change ng/L), and the 0/1-hour algorithm recommended in the European Society of Cardiology guideline combining LOD and 1-hour algorithm. Among 2828 enrolled patients, acute myocardial infarction was the final diagnosis in 451 (16%) patients. The LOD approach ruled out 453 patients (16%) with a sensitivity of 100% (95% confidence interval [CI], 99.2%–100%), the single cutoff 1516 patients (54%) with a sensitivity of 97.1% (95% CI, 95.1%–98.3%), the 1-hour algorithm 1459 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%–99.2%), and the 0/1-hour algorithm 1463 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%–99.2%). Predefined subgroup analysis in early presenters (≤2 hours) revealed significantly lower sensitivity (94.2%, interaction P =0.03) of the single cutoff, but not the other strategies. Two-year survival was 100% with LOD and 98.1% with the other strategies ( P .01 for LOD versus each of the other strategies). All 4 rule-out strategies balance effectiveness and safety equally well. The single cutoff should not be applied in early presenters, whereas the 3 other strategies seem to perform well in this challenging subgroup. URL: www.clinicaltrials.gov . Unique identifier: NCT00470587.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.IJCARD.2019.04.088
Abstract: To assess the prognostic performance of Growth differentiation factor-15 (GDF-15) concentrations in unselected patients presenting with suspected acute myocardial infarction (AMI) and adjudication based on high-sensitivity cardiac troponin (hs-cTn). In an ongoing prospective multicenter diagnostic study, consecutive patients presenting with suspected AMI to the emergency department and available GDF-15 and hs-cTnT concentrations were included. Adjudication of AMI was performed central by two independent cardiologists using all available clinical information including cardiac imaging and serial hs-cTn concentrations. Overall, 718 patients were included, with 23% (162/718) having an adjudicated diagnosis of AMI. The cumulative incidence of death within 2 years was 19% in patients with AMI (30 deaths in 162 patients) versus 5% in patients without AMI (25 deaths in 556 patients P < 0.001). In AMI patients, GDF-15 provided an AUC of 0.89 (95% confidence interval [CI] 0.83-0.94) for 2-year death versus 0.55 (95% CI 0.44-0.66) for hs-cTnT (P < 0.001). A GDF-15 cutoff of ≤1560 ng/L predicted 2-year survival in 47% (76/162) of AMI patients and had 100% sensitivity (95% CI 88-100%) for 2-year death. In patients without AMI, GDF-15 provided an AUC of 0.83 (95% CI 0.76-0.89) versus 0.76 (95% CI 0.67-0.85) for hs-cTnT (P = 0.096). A GDF-15 cutoff of ≤886 ng/L predicted 2-year survival in 37% (203/556) of non-AMI patients and had 100% sensitivity (95% CI 86-100%) for 2-year death. GDF-15 concentrations at emergency department presentation have a high predictive accuracy for all-cause death in patients with suspected AMI and allow the identification of a large proportion of AMI patients with very low mortality risk.
Publisher: BMJ
Date: 24-04-2019
DOI: 10.1136/HEARTJNL-2018-314305
Abstract: Assess the relative incidence and compare characteristics and outcome of unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI). 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. 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). The relative incidence and mortality of UA is substantially lower than that of NSTEMI, while the rate of future non-fatal MI is similar.
Publisher: Springer Science and Business Media LLC
Date: 12-07-2016
DOI: 10.1007/S00392-016-1020-Y
Abstract: It is unknown whether higher rates of delayed diagnosis and misdiagnosis of acute coronary syndrome (ACS) in women might have contributed to the poorer outcome of women. In a prospective diagnostic multicenter study, we recruited patients presenting to the emergency department (ED) with any kind of chest discomfort/chest pain with onset or peak within the last 12 h. We quantified early diagnostic uncertainty for the presence of ACS among treating physicians at the ED after 90 min, possibly responsible for delayed diagnosis, using a visual analogue scale. Late diagnostic uncertainty, possibly responsible for misdiagnosis, was defined as disagreement among two independent cardiologists' adjudication of the final diagnosis after complete work-up. Among 2795 patients (897 women and 1898 men), ACS was the adjudicated final diagnosis in 24 % of women and 35 % of men. Early diagnostic accuracy of clinical judgment of the ED physician for ACS as quantified by the area under the receiver-operating characteristics curve was 0.89 (95 % CI 0.87-0.92) in women and 0.86 (95 % CI 0.85-0.88) in men (p = 0.046). Late diagnostic uncertainty regarding the diagnosis of ACS was 5 % in women and 7 % in men (p = 0.069). Diagnostic uncertainty for the presence of ACS in women is not more common as compared to men and does, therefore, not explain the poorer outcome observed in women with ACS. URL: www.clinicaltrials.gov . Unique identifier: NCT00470587.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.IJCARD.2018.11.140
Abstract: 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. 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. 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%). 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. NCT00470587, how/NCT00470587.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.IJCARD.2017.02.079
Abstract: Exercise ECG stress testing is the most widely available method for evaluation of patients with suspected myocardial ischemia. Its major limitation is the relatively poor accuracy of ST-segment changes regarding ischemia detection. Little is known about the optimal method to assess ST-deviations. A total of 1558 consecutive patients undergoing bicycle exercise stress myocardial perfusion imaging (MPI) were enrolled. Presence of inducible myocardial ischemia was adjudicated using MPI results. The diagnostic value of ST-deviations for detection of exercise-induced myocardial ischemia was systematically analyzed 1) for each in idual lead, 2) at three different intervals after the J-point (J+40ms, J+60ms, J+80ms), and 3) at different time points during the test (baseline, maximal workload, 2min into recovery). Exercise-induced ischemia was detected in 481 (31%) patients. The diagnostic accuracy of ST-deviations was highest at +80ms after the J-point, and at 2min into recovery. At this point, ST- litude showed an AUC of 0.63 (95% CI 0.59-0.66) for the best-performing lead I. The combination of ST- litude and ST-slope in lead I did not increase the AUC. Lead I reached a sensitivity of 37% and a specificity of 83%, with similar sensitivity to manual ECG analysis (34%, p=0.31) but lower specificity (90%, p<0.001). When using ECG stress testing for evaluation of patients with suspected myocardial ischemia, the diagnostic accuracy of ST-deviations is highest when evaluated at +80ms after the J-point, and at 2min into recovery.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.JACC.2019.06.025
Abstract: 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. 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. 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. 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. 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).
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JACC.2017.07.774
Abstract: Uncertainties regarding the most appropriate definition and treatment of type 2 myocardial infarction (T2MI) due to supply-demand mismatch have contributed to inconsistent adoption in clinical practice. This study sought a better understanding of the effect of the definition of T2MI on its incidence, treatment, and event-related mortality, thereby addressing an important unmet clinical need. The final diagnosis was adjudicated in patients presenting with symptoms suggestive of myocardial infarction by 2 independent cardiologists by 2 methods: 1 method required the presence of coronary artery disease, a common interpretation of the 2007 universal definition (T2MI Overall, 4,015 consecutive patients were adjudicated. The incidence of T2MI based on the T2MI T2MI
Publisher: Oxford University Press (OUP)
Date: 07-2019
DOI: 10.1373/CLINCHEM.2018.300061
Abstract: The aim of this study was to validate the clinical performance of the Beckman Access high-sensitivity cardiac troponin I (hs-cTnI) assay. 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. 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. 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.
Publisher: American College of Physicians
Date: 29-01-2019
DOI: 10.7326/M18-1967
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-07-2018
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.IJCARD.2016.01.112
Abstract: The novel high-sensitivity cardiac troponin (hs-cTn) 0h/1h-algorithm substantially improves the early triage of patient's assigned "rule-out" or "rule-in" of acute myocardial infarction (AMI), while diagnostic uncertainty remains in that 25-30% of patients assigned to "observe". We aimed to better characterize these patients. In a prospective multicenter diagnostic study, we applied the hs-cTnT 0h/1h-algorithm in 2213 unselected patients presenting with symptoms suggestive of AMI to the emergency department. The final diagnosis was adjudicated by two independent cardiologists using all available information. Survival at 720-days was the prognostic endpoint. Findings were validated using a hs-cTnI 0h/1h-algorithm. Twenty-four percent (n=523) of patients were assigned to "observe" by the hs-cTnT 0h/1h-algorithm. These patients differed significantly in multiple characteristics from "rule-out" and "rule-in" patients: they were older, in 75% male, and very often (57%) had pre-existing coronary artery disease (CAD). Diagnostic uncertainty for the presence of an AMI/UA was high. Only 39% of patients were suitable for coronary computed tomography angiography (CCTA). The most common final adjudicated diagnoses were non-cardiac disease (38%), non-coronary cardiac disease (24%), unstable angina (UA, 21%), and AMI (15%). Absolute hs-cTnT-changes within 3h had the highest diagnostic accuracy for AMI (AUC 0.86). Cumulative 720-day survival rate was 86%, which was significantly lower as compared to "rule-out" (p<0.001) and comparable to "rule-in" (p=ns). Findings were similar for the hs-cTnI "observe" zone. "Observe" patients are typically elderly men with pre-existing CAD and high long-term mortality. Absolute hs-cTn-changes within 3h, functional stress imaging and coronary angiography are the key diagnostic modalities.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.JACC.2019.06.020
Abstract: 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. This study sought to determine the prevalence of PE in patients with syncope. 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. 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%). 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).
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.IJCARD.2018.05.136
Abstract: High-sensitivity cardiac troponin T (hs-cTnT) blood concentrations were shown to exhibit a diurnal rhythm, characterized by gradually decreasing concentrations throughout daytime, rising concentrations during nighttime and peak concentrations in the morning. We aimed to investigate whether this also applies to (h)s-cTnI assays and whether it would affect diagnostic accuracy for acute myocardial infarction (AMI). Blood concentrations of cTnI were measured at presentation and after 1 h using four different cTnI assays: three commonly used sensitive (s-cTnI Architect, Ultra and Accu) and one experimental high-sensitivity assay (hs-cTnI Accu) in a prospective multicenter diagnostic study of patients presenting to the emergency department with suspected AMI. These concentrations and their diagnostic accuracy for AMI (quantified by the area under the curve (AUC)) were compared between morning (11 p.m. to 2 p.m.) and evening (2 p.m. to 11 p.m.) presenters. Among 2601 patients, AMI was the final diagnosis in 17.6% of patients. Concentrations of (h)s-cTnI as measured using all four assays were comparable in patients presenting in the morning versus patients presenting in the evening. Diagnostic accuracy for AMI of all four (h)s-cTnI assays were high and comparable between patients presenting in the morning versus presenting in the evening (AUC at presentation: 0.90 vs 0.93 for s-cTnI Architect 0.91 vs 0.94 for s-cTnI Ultra 0.89 vs 0.94 for s-cTnI Accu 0.91 vs 0.94 for hs-cTnI Accu). Cardiac TnI does not seem to express a diurnal rhythm. Diagnostic accuracy for AMI is very high and does not differ with time of presentation. NCT00470587, how/NCT00470587.
Location: Saudi Arabia
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Nikola Kozhuharov.