Emel Kaplan

Background: Diagnosing myocardial infarction in patients with prior coronary artery bypass grafting (CABG) remains challenging, primarily because of lower diagnostic accuracy of high‐sensitivity cardiac troponin (hs‐cTn). cMyC (cardiac myosin‐binding protein C), because of its faster release kinetics and greater abundance, may offer improved diagnostic performance in this population. Methods: The diagnostic accuracy of cMyC was directly compared with that of hs‐cTnT and hs‐cTnI in a prospective, international, multicenter, diagnostic study enrolling adult patients presenting to the emergency department with acute chest discomfort. Final diagnoses were centrally adjudicated by 2 independent cardiologists using all available clinical and study‐specific data, including imaging and serial hs‐cTnT measurements. Patients were stratified according to the presence or absence of prior CABG. Results: Among 4752 patients, 387 (8%) had prior CABG (median age, 75 years; 86% men). The incidence of myocardial infarction was significantly higher in patients with prior CABG (38% versus 16%; P <0.001). In the CABG group, the diagnostic accuracy of cMyC as quantified by the area under the curve was 0.88 (95% CI, 0.85–0.92), which was comparable but not superior to that of hs‐cTnT (0.89 [95% CI, 0.86–0.92]) and hs‐cTnI (0.88 [95% CI, 0.84–0.91]). These findings were consistent across alternative high‐sensitivity cMyC assays. Conclusions: In patients with prior CABG, cMyC demonstrated high diagnostic accuracy for myocardial infarction, but not superior to established hs‐cTnT and hs‐cTnI assays. Registration: URL: clinicaltrials.gov ; Unique Identifier: NCT00470587.

Background: The European Society of Cardiology (ESC) 0/1h‐high‐sensitivity cardiac troponin (hs‐cTn)T/I‐algorithms have lower efficacy in patients with prior coronary artery bypass grafting. We hypothesized that in these high‐risk patients, the longer time to the second blood draw within the ESC 0/2h‐hs‐cTn‐algorithms would increase efficacy, defined as the proportion of patients triaged to rule‐in/out of myocardial infarction, versus the ESC‐0/1h‐hs‐cTn‐algorithms. Methods: In a prospective international multicenter diagnostic study including patients presenting to the emergency department with acute chest discomfort, final diagnoses were centrally adjudicated according to the Universal Definition of Myocardial Infarction. Safety and efficacy of the guideline‐recommended ESC 0/1h‐ and 0/2h‐hs‐cTn‐algorithms using assay‐specific use‐optimized cut‐offs were directly compared in patients with prior coronary artery bypass grafting. Findings were externally validated in an independent prospective US multicenter study. Results: Among 356 patients (median [interquartile range] age 73 [64–80] years, prevalence of non–ST‐segment–elevation myocardial infarction [NSTEMI]: 31% [n=112]), sensitivity for rule‐out of NSTEMI was high for the ESC 0/1h‐ and 0/2h‐hs‐cTnT‐Elecsys‐algorithms (0/1h: 100% [95% CI 96.7–100]; 0/2h: Sensitivity: 99.1% [95% CI 95.1–99.8]). Specificity for rule‐in of NSTEMI was also high (0/1h: 97.1% [95% CI 94.2–98.6]; 0/2h 98.4% [95% CI 95.9–99.4]). Efficacy was 50.6% for 0/1h and 58.4% for 0/2h (difference: 7.9% [95% CI 4.2–11.5]). Findings with higher efficacy for 0/2h versus 0/1h were confirmed using hs‐cTnI‐Architect (difference in efficacy 3.1% [95% CI 0.1–6.1]) and using hs‐cTnI‐Atellica in the external validation cohort (n=178; difference in efficacy 9% [95% CI 4.5–13.5]). Conclusions: The ESC 0/2h‐hs‐cTn‐algorithms have higher efficacy and comparable safety versus the ESC 0/1h‐hs‐cTn‐algorithms in patients with prior coronary artery bypass grafting. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT00470587.

Background: There is major uncertainty among physicians on how to best use the novel hs‐cTnI (high sensitivity‐cardiac troponin I)‐VITROS assay, as the limit of quantification (2 ng/L), applied by the US Food and Drug Administration and other regulators, is higher than the limit of detection (1 ng/L)‐based rule‐out cutoffs from recent pilot studies for 0/1‐hour and 0/2‐hour algorithms. Methods: This prospective, multicenter study aimed to derive and validate higher limit of quantification‐based assay‐specific cutoffs for safe and efficient rule‐out of myocardial infarction among adult patients presenting with acute chest discomfort to the emergency department. Final diagnoses of myocardial infarction were centrally adjudicated by 2 independent cardiologists, blinded to hs‐cTnI‐VITROS concentrations. Results: Among 2931 eligible patients, 467 (16%) were diagnosed with myocardial infarction. In the derivation cohort (n=1466), a cutoff ≤2 ng/L at presentation in patients with chest pain onset >3 hours (direct rule‐out) and ≤2 ng/L in combination with a 1‐hour absolute change of ≤1 ng/L ruled out 51% of patients, with a sensitivity of 99.1% (96.9%–99.8%). Predefined rule‐in thresholds (0 hour‐value ≥40 ng/L [direct rule‐in] or an absolute change within 1 hour of ≥4 ng/L) identified 16.9% of patients, with a specificity of 95.9% (94.7%–96.9%). Very high sensitivity and specificity were confirmed in the validation cohort (n=1465). Comparable findings were observed for the alternative 0/2‐hour algorithm with ≤2 ng/L as the rule‐out threshold. Conclusions: The alternative 0/1‐hour and 0/2‐hour algorithms using limit of quantification‐based rule‐out cutoffs of ≤2 ng/L with the hs‐cTnI‐VITROS assay demonstrated very high safety and efficacy in suspected myocardial infarction. Registration: URL: https://www.clinicaltrials.gov/ ; Identifier: NCT00470587.

Aims: Cardiac autonomic dysfunction is associated with an adverse prognosis in patients with atrial fibrillation (AF). However, the association of AF itself with cardiac autonomic function (CAF) remains unclear. We aimed to investigate whether CAF, assessed by heart rate variability (HRV), differs across patients with and without AF. Methods and results: We enrolled patients from a prospective multicentre study (Swiss-AF) with a 5-min resting ECG recording in SR or AF without pacing. Cardiac autonomic function was quantified by periodic repolarization dynamics (PRD), a marker of sympathetic activity, and by conventional HRV parameters. We included 2289 patients, 807 (35%) SR patients, 932 (41%) AF patients with SR ECGs (AF-SR), and 550 (24%) AF patients with AF ECGs (AF-AF). Mean age was 74 vs. 70 vs. 75 years; 37%, 31%, and 24% were female. Median PRD was 4.8 deg (IQR 2.6–6.7) in the SR group, 5.1 deg (IQR 2.9–6.9) in the AF-SR group, and 7.0 deg (IQR 5.8–8.4) in the AF–AF group (P < 0.001). After full adjustment (SR group = reference group), the AF–AF group showed a stronger association with elevated PRD (β-coefficient 2.10, 95% CI 1.79–2.41, P < 0.001) than the AF–SR group (β-coefficient 0.36, 95% CI 0.08–0.64, P = 0.011). Most other HRV parameters indicated greater autonomic impairment in the AF–SR group compared to the SR group. Conclusion: Atrial fibrillation was associated with increased sympathetic activity, with the greatest impairment observed in patients during AF, independent of cardiovascular risk factors. Periodic repolarization dynamics may represent a useful marker for the assessment of CAF in AF patients.

Background: There is uncertainty among physicians regarding the optimal clinical application of the novel high-sensitivity cardiac troponin I (hs-cTnI)-VITROS assay within the widely implemented upper reference limit (URL)-based ESC 0/3h-algorithm. Methods: This prospective, international, multicenter study aimed to validate and compare different modifications of the URL-based ESC 0/3h-algorithm among adult patients presenting with suspected acute myocardial infarction (AMI) to the emergency department. Final diagnoses of AMI were centrally adjudicated by two independent cardiologists, blinded to hs-cTnI-VITROS concentrations. Discrimination was compared to the best validated hs-cTnT/I-assays. Clinical follow-up for cardiovascular death and AMI was conducted until five years. Results: Among 1225 eligible patients (median age 63 years (IQR 52-75), 31.9% women), 18.9% were adjudicated as NSTEMI. Diagnostic discrimination of hs-cTnI-VITROS at 0h was very high (AUC 0.949, 95% CI 0.941–0.958), and comparable to hs-cTnI-Architect and hs-cTnT-Elecsys. Using the ESC 0/3h algorithm, 30.9% of patients were classified as rule-out (sensitivity 99.1%, NPV 99.5%) and 19.0% as rule-in (specificity 96.0%, PPV 82.8%). Substituting the HEART score for the GRACE score increased rule-out efficacy to 43.9%, while maintaining very high safety (sensitivity 99.6%; NPV 99.8%). Findings were consistent across predefined subgroups, in sensitivity analyses restricted to type 1 NSTEMI, using the 2h study blood sample (n=2249), and for the composite of cardiovascular death or AMI during five-year follow-up. Conclusions: The ESC 0/3h-algorithm demonstrated excellent performance for rule-out of NSTEMI with greater efficacy when combined with the HEART-instead of the GRACE score. Registration: https://clinicaltrials.gov/study/NCT00470587 Clinical Perspective: What Is New?: In a prospective, international multicenter cohort, the URL-based ESC 0/3h algorithm using the FDA-cleared hs-cTnI-VITROS assay achieved very high rule-out safety (sensitivity 99.1%, NPV 99.5%) but limited efficacy (30.9% rule-out) when combined with GRACE score <140 and symptom resolution. Replacing GRACE with a HEART score (<5) increased rule-out efficacy to 43.9% while maintaining excellent safety (sensitivity 99.6%, NPV 99.8%), with consistent findings across subgroups, sensitivity analyses, and long-term outcomes. What Are the Clinical Implications?: Clinicians and health systems using hs-cTnI-VITROS can apply the ESC 0/3h algorithm with assay-conform decision values; adding clinical risk stratification is necessary to meet contemporary rule-out safety targets.