Machine Learning for Myocardial Infarction Compared With Guideline-Recommended Diagnostic Pathways.

BACKGROUND: Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) is a validated clinical decision support tool that uses machine learning with or without serial cardiac troponin measurements at a flexible time point to calculate the probability of myocardial infarction (MI). How CoDE-ACS performs at different time points for serial measurement and compares with guideline-recommended diagnostic pathways that rely on fixed thresholds and time points is uncertain. METHODS: Patients with possible MI without ST-segment-elevation were enrolled at 12 sites in 5 countries and underwent serial high-sensitivity cardiac troponin I concentration measurement at 0, 1, and 2 hours. Diagnostic performance of the CoDE-ACS model at each time point was determined for index type 1 MI and the effectiveness of previously validated low- and high-probability scores compared with guideline-recommended European Society of Cardiology (ESC) 0/1-hour, ESC 0/2-hour, and High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome) pathways. RESULTS: In total, 4105 patients (mean age, 61 years [interquartile range, 50-74]; 32% women) were included, among whom 575 (14%) had type 1 MI. At presentation, CoDE-ACS identified 56% of patients as low probability, with a negative predictive value and sensitivity of 99.7% (95% CI, 99.5%-99.9%) and 99.0% (98.6%-99.2%), ruling out more patients than the ESC 0-hour and High-STEACS (25% and 35%) pathways. Incorporating a second cardiac troponin measurement, CoDE-ACS identified 65% or 68% of patients as low probability at 1 or 2 hours, for an identical negative predictive value of 99.7% (99.5%-99.9%); 19% or 18% as high probability, with a positive predictive value of 64.9% (63.5%-66.4%) and 68.8% (67.3%-70.1%); and 16% or 14% as intermediate probability. In comparison, after serial measurements, the ESC 0/1-hour, ESC 0/2-hour, and High-STEACS pathways identified 49%, 53%, and 71% of patients as low risk, with a negative predictive value of 100% (99.9%-100%), 100% (99.9%-100%), and 99.7% (99.5%-99.8%); and 20%, 19%, or 29% as high risk, with a positive predictive value of 61.5% (60.0%-63.0%), 65.8% (64.3%-67.2%), and 48.3% (46.8%-49.8%), resulting in 31%, 28%, or 0%, who require further observation in the emergency department, respectively. CONCLUSIONS: CoDE-ACS performs consistently irrespective of the timing of serial cardiac troponin measurement, identifying more patients as low probability with comparable performance to guideline-recommended pathways for MI. Whether care guided by probabilities can improve the early diagnosis of MI requires prospective evaluation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00470587.

External validation of the 0/1h-algorithm and derivation of a 0/2h-algorithm using a new point-of-care Hs-cTnI assay.

BACKGROUND: The high-sensitivity cardiac troponin (hs-cTn) I point-of-care (POC) hs-cTnI-PATHFAST assay has recently become clinically available. METHODS: We aimed to externally validate the hs-cTnI-PATHFAST 0/1h-algorithm recently developed for the early diagnosis of non-ST-segment-elevation myocardial infarction (NSTEMI) and derive and validate a 0/2-algorithm in patients presenting to the emergency department with acute chest discomfort included in a multicenter diagnostic study. Two independent cardiologists centrally adjudicated the final diagnoses using all the clinical and study-specific information available including serial measurements of hs-cTnI-Architect. RESULTS: Among 1,532 patients (median age 60 years, 33% [n = 501] women), NSTEMI was the final diagnosis in 13%. External validation of the hs-cTnI-PATHFAST 0/1h-algorithm showed very high negative predictive value (NPV; 100% [95%CI, 99.5%-100%]) and sensitivity 100% (95%CI, 98.2%-100%) for rule-out of NSTEMI. Positive predictive value (PPV) and specificity for rule-in of NSTEMI were high (74.9% [95%CI, 68.3%-80.5%] and 96.4% [95%CI, 95.2%-97.3%], respectively). Among 1,207 patients (median age 61 years, 32% [n = 391] women) available for the derivation (n = 848) and validation (n = 359) of the hs-cTnI-PATHFAST 0/2h-algorithm, a 0h-concentration <3 ng/L or a 0h-concentration <4 ng/L with a 2h-delta <4ng/L ruled-out NSTEMI in 52% of patients with a NPV of 100% (95%CI, 98-100) and sensitivity of 100% (95%CI, 92.9%-100%) in the validation cohort. A 0h-concentration ≥90ng/L or a 2h-delta ≥ 55ng/L ruled-in 38 patients (11%): PPV 81.6% (95%CI, 66.6-90.8), specificity 97.7% (95%CI, 95.4-98.9%). CONCLUSIONS: The POC hs-cTnI-PATHFAST assay allows rapid and effective rule-out and rule-in of NSTEMI using both a 0/1h- and a 0/2h-algorithm with high NPV/sensitivity for rule-out and high PPV/specificity for rule-in. CLINICAL TRIAL REGISTRATION: NCT00470587.

Troponin in early presenters to rule out myocardial infarction.

AIMS: Whether a single cardiac troponin measurement can safely rule out myocardial infarction in patients presenting within a few hours of symptom onset is uncertain. The study aim was to assess the performance of troponin in early presenters. METHODS AND RESULTS: In patients with possible myocardial infarction, the diagnostic performance of a single measurement of high-sensitivity cardiac troponin I at presentation was evaluated and externally validated in those tested ≤3, 4-12, and >12 h from symptom onset. The limit-of-detection (2 ng/L), rule-out (5 ng/L), and sex-specific 99th centile (16 ng/L in women; 34 ng/L in men) thresholds were compared. In 41 103 consecutive patients [60 (17) years, 46% women], 12 595 (31%) presented within 3 h, and 3728 (9%) had myocardial infarction. In those presenting ≤3 h, a threshold of 2 ng/L had greater sensitivity and negative predictive value [99.4% (95% confidence interval 99.2%-99.5%) and 99.7% (99.6%-99.8%)] compared with 5 ng/L [96.5% (96.2%-96.8%) and 99.3% (99.1%-99.4%)]. In those presenting ≥3 h, the sensitivity and negative predictive value were similar for both thresholds. The sensitivity of the 99th centile was low in early and late presenters at 71.4% (70.6%-72.2%) and 92.5% (92.0%-93.0%), respectively. Findings were consistent in an external validation cohort of 7088 patients. CONCLUSION: In early presenters, a single measurement of high-sensitivity cardiac troponin I below the limit of detection may facilitate the safe rule out of myocardial infarction. The 99th centile should not be used to rule out myocardial infarction at presentation even in those presenting later following symptom onset.

Diagnostic discrimination of a novel high-sensitivity cardiac troponin I assay and derivation/validation of an assay-specific 0/1h-algorithm.

BACKGROUND: We aimed to assess the diagnostic utility of the Dimension EXL LOCI High-Sensitivity Troponin I (hs-cTnI-EXL) assay. METHODS: This multicenter study included patients with chest discomfort presenting to the emergency department. Diagnoses were centrally and independently adjudicated by two cardiologists using all available clinical information. Adjudication was performed twice including serial measurements of high-sensitivity cardiac troponin (hs-cTn) I-Architect (primary analysis) and serial measurements of hs-cTnT-Elecsys (secondary analysis) in addition to the clinically used (hs)-cTn. The primary objective was to assess and compare the discriminatory performance of hs-cTnI-EXL, hs-cTnI-Architect and hs-cTnT-Elecsys for acute myocardial infarction (MI). Furthermore, we derived and validated a hs-cTnI-EXL-specific 0/1h-algorithm. RESULTS: Adjudicated MI was the diagnosis in 204/1454 (14%) patients. The area under the receiver operating characteristics curve for hs-cTnI-EXL was 0.94 (95%CI, 0.93-0.96), and comparable to hs-cTnI-Architect (0.95; 95%CI, 0.93-0.96) and hs-cTnT-Elecsys (0.93; 95%CI, 0.91-0.95). In the derivation cohort (n = 813), optimal criteria for rule-out of MI were <9ng/L at presentation (if chest pain onset >3h) or <9ng/L and 0h-1h-change <5ng/L, and for rule-in ≥160ng/L at presentation or 0h-1h-change ≥100ng/L. In the validation cohort (n = 345), these cut-offs ruled-out 56% of patients (negative predictive value 99.5% (95%CI, 97.1-99.9), sensitivity 97.8% (95%CI, 88.7-99.6)), and ruled-in 9% (positive predictive value 83.3% (95%CI, 66.4-92.7), specificity 98.3% (95%CI, 96.1-99.3)). Secondary analyses using adjudication based on hs-cTnT measurements confirmed the findings. CONCLUSIONS: The overall performance of the hs-cTnI-EXL was comparable to best-validated hs-cTnT/I assays and an assay-specific 0/1h-algorithm safely rules out and accurately rules in acute MI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00470587.

Hyperacute T Wave in the Early Diagnosis of Acute Myocardial Infarction.

STUDY OBJECTIVE: The diagnostic performance of T-wave amplitudes for the detection of myocardial infarction is largely unknown. We aimed to address this knowledge gap. METHODS: T-wave amplitudes were automatically measured in 12-lead ECGs of patients presenting with acute chest discomfort to the emergency department within a prospective diagnostic multicenter study. The final diagnosis was centrally adjudicated by 2 independent cardiologists. Patients with left ventricular hypertrophy, complete left bundle branch block, or paced ventricular depolarization were excluded. The performance for lead-specific 95th-percentile thresholds were reported as likelihood ratios (lr), specificity, and sensitivity. RESULTS: Myocardial infarction was the final diagnosis in 445 (18%) of 2457 patients. In most leads, T-wave amplitudes tended to be greater in patients without myocardial infarction than those with myocardial infarction, and T-wave amplitude exceeding the 95th percentile had positive and negative lr close to 1 or with confidence intervals (CIs) crossing 1. The exceptions were leads III, aVR, and V1, which had positive lrs of 3.8 (95% CI, 2.7 to 5.3), 4.3 (95% CI, 3.1 to 6.0) and 2.0 (95% CI, 1.4 to 2.9), respectively. These leads normally have inverted T waves, so T-wave amplitude exceeding the 95th percentile reflects upright rather than increased-amplitude hyperacute T waves. CONCLUSION: Hyperacute T waves, when defined as increased T-wave amplitude exceeding the 95th percentile, did not provide useful information in diagnosing myocardial infarction in this sample.

Strong German Hearts 2023: A Field Report.

What do the special forces of the Federal Police and heart surgeons have in common? To find out, a team of the German Society for Thoracic and Cardiovascular Surgery (DGTHG) started a pilot project called "Strong German Hearts" with an intensive 36-hour training supported by the special forces of the Federal Police.

Five-Year Survival of Patients Treated with Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) Compared with the General Swiss Population.

BACKGROUND: To evaluate the midterm follow-up and 5-year survival outcome of the minimally invasive direct coronary artery bypass (MIDCAB) procedure compared with the survival of the general Swiss population. METHODS: Retrospective study on preoperative data, intraoperative data, and postoperative outcome of patients who underwent MIDCAB surgery between June 2010 and February 2019. To assess validity of this surgical therapy, outcomes were compared with survival data of a gender- and age-matched cohort of the general Swiss population taken from the database of the Swiss Federal Statistical Office. RESULTS: A total of 88 patients were included. Median (interquartile range [IQR[) age was 66 (56-75) years, and 27% (n = 24) were female. The median (IQR) length of the in-hospital stay was 7 (6-8) days. No postoperative stroke occurred. The 30-day mortality was 1.1% (n = 1). Reintervention for failed left internal mammary artery was needed in 1.1% (n = 1). The median (IQR) ejection fraction was 58% (47-60) preoperatively and remained stable during follow-up. The median (IQR) follow-up period was 3 (1.1-5.2) years. Five years postoperatively, 83% (confidence interval, 69-91) of the patients were alive, showing an overlap with the range of survival of the matched subcohort of the general Swiss population (range, 84-100%). CONCLUSION: Though suffering from coronary heart disease, patients after MIDCAB show almost equal survival rates as an equivalent subcohort corresponding to the general Swiss population matched on age and gender. Thus, our data show this treatment to be safe and beneficial.

International Validation of the Canadian Syncope Risk Score : A Cohort Study.

BACKGROUND: The Canadian Syncope Risk Score (CSRS) was developed to predict 30-day serious outcomes not evident during emergency department (ED) evaluation. OBJECTIVE: To externally validate the CSRS and compare it with another validated score, the Osservatorio Epidemiologico della Sincope nel Lazio (OESIL) score. DESIGN: Prospective cohort study. SETTING: Large, international, multicenter study recruiting patients in EDs in 8 countries on 3 continents. PARTICIPANTS: Patients with syncope aged 40 years or older presenting to the ED within 12 hours of syncope. MEASUREMENTS: Composite outcome of serious clinical plus procedural events (primary outcome) and the primary composite outcome excluding procedural interventions (secondary outcome). RESULTS: Among 2283 patients with a mean age of 68 years, the primary composite outcome occurred in 7.2%, and the composite outcome excluding procedural interventions occurred in 3.1% at 30 days. Prognostic performance of the CSRS was good for both 30-day composite outcomes and better compared with the OESIL score (area under the receiver-operating characteristic curve [AUC], 0.85 [95% CI, 0.83 to 0.88] vs. 0.74 [CI, 0.71 to 0.78] and 0.80 [CI, 0.75 to 0.84] vs. 0.69 [CI, 0.64 to 0.75], respectively). Safety of triage, as measured by the frequency of the primary composite outcome in the low-risk group, was higher using the CSRS (19 of 1388 [0.6%]) versus the OESIL score (17 of 1104 [1.5%]). A simplified model including only the clinician classification of syncope (cardiac syncope, vasovagal syncope, or other) variable at ED discharge-a component of the CSRS-achieved similar discrimination as the CSRS (AUC, 0.83 [CI, 0.80 to 0.87] for the primary composite outcome). LIMITATION: Unable to disentangle the influence of other CSRS components on clinician classification of syncope at ED discharge. CONCLUSION: This international external validation of the CSRS showed good performance in identifying patients at low risk for serious outcomes outside of Canada and superior performance compared with the OESIL score. However, clinician classification of syncope at ED discharge seems to explain much of the performance of the CSRS in this study. The clinical utility of the CSRS remains uncertain. PRIMARY FUNDING SOURCE: Swiss National Science Foundation & Swiss Heart Foundation.

Novel Criteria for the Observe-Zone of the ESC 0/1h-hs-cTnT Algorithm.

BACKGROUND: The non-ST-segment-elevation myocardial infarction (NSTEMI) guidelines of the European Society of Cardiology (ESC) recommend a 3h cardiac troponin determination in patients triaged to the observe-zone of the ESC 0/1h-algorithm; however, no specific cutoff for further triage is endorsed. Recently, a specific cutoff for 0/3h high-sensitivity cardiac troponin T (hs-cTnT) change (7 ng/L) was proposed, warranting external validation. METHODS: Patients presenting with acute chest discomfort to the emergency department were prospectively enrolled into an international multicenter diagnostic study. Final diagnoses were centrally adjudicated by 2 independent cardiologists applying the fourth universal definition of myocardial infarction, on the basis of complete cardiac workup, cardiac imaging, and serial hs-cTnT. Hs-cTnT concentrations were measured at presentation, after 1 hour, and after 3 hours. The objective was to externally validate the proposed cutoff, and if necessary, derive and internally as well as externally validate novel 0/3h-criteria for the observe-zone of the ESC 0/1h-hs-cTnT-algorithm in an independent multicenter cohort. RESULTS: Among 2076 eligible patients, application of the ESC 0/1h-hs-cTnT-algorithm triaged 1512 patients (72.8%) to either rule out or rule in NSTEMI, leaving 564 patients (27.2%) in the observe-zone (adjudicated NSTEMI prevalence, 120/564 patients, 21.3%). The suggested 0/3h-hs-cTnT-change of <7 ng/L triaged 517 patients (91.7%) toward rule-out, resulting in a sensitivity of 33.3% (95% CI, 25.5-42.2), missing 80 patients with NSTEMI, and ≥7 ng/L triaged 47 patients toward rule-in (8.3%), resulting in a specificity of 98.4% (95% CI, 96.8-99.2). Novel derived 0/3h-criteria for the observe-zone patients ruled out NSTEMI with a 3h hs-cTnT concentration <15 ng/L and a 0/3h-hs-cTnT absolute change <4 ng/L, triaging 138 patients (25%) toward rule-out, resulting in a sensitivity of 99.2% (95% CI, 96.0-99.9), missing 1 patient with NSTEMI. A 0/3h-hs-cTnT absolute change ≥6 ng/L triaged 63 patients (11.2%) toward rule-in, resulting in a specificity of 98% (95% CI, 96.2-98.9) Thereby, the novel 0/3h-criteria reduced the number of patients in the observe zone by 36%s and the number of type 1 myocardial infarction by 50%. Findings were confirmed in both internal and external validation. CONCLUSIONS: A combination of a 3h-hs-cTnT concentration (<15 ng/L) and a 0/3h absolute change (<4 ng/L) is necessary to safely rule out NSTEMI in patients remaining in the observe-zone of the ESC 0/1h-hs-cTnT-algorithm. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT00470587.

Soluble urokinase plasminogen activator receptor and functionally relevant coronary artery disease: a prospective cohort study.

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging biomarker associated with anatomical CAD burden and cardiovascular outcomes including myocardial infarction (MI) and death. We aimed to validate previous findings of the prognostic value of suPAR and to evaluate its diagnostic potential for functional relevant CAD (fCAD). METHODS: Consecutive patients with suspected fCAD were enrolled. Adjudication of fCAD was performed blinded to suPAR concentrations by myocardial perfusion single-photon emission tomography (MPI-SPECT) and coronary angiography. Prognostic outcome measures included all-cause death, cardiovascular death, and incident MI during 2-year follow-up. RESULTS: Among consecutive 968 patients, suPAR concentrations were higher in patients with fCAD compared to those without (3.45 vs. 3.20 ng/mL, p = 0.007), but did not provide acceptable diagnostic accuracy (area under the curve [AUC]: 0.56, 95%CI 0.52-0.60). SuPAR correlated with high-sensitivity cardiac-troponin T (Spearman's rho (ρ) 0.393, p < 0.001), NT-proBNP (ρ = 0.327, p < 0.001), age (ρ = 0.364, p < 0.001) and very weakly with coronary atherosclerosis (ρ = 0.123, p < 0.001). Prognostic discrimination of suPAR was moderate for cardiovascular death (AUC = 0.72, 95%CI 0.62-0.81) and all-cause death (AUC = 0.72, 95%CI 0.65-0.79) at 2-years. SuPAR remained a significant predictor for all-cause death in multivariable Cox regression (HR = 1.96, p = 0.001). CONCLUSIONS: SuPAR was an independent predictor of all-cause death, without diagnostic utility for fCAD. CLINICAL TRIAL REGISTRATION: NCT01838148.

Robot-assisted vs. laparoscopic repair of complete upside-down stomach hiatal hernia (the RATHER-study): a prospective comparative single center study.

BACKGROUND: Complete upside-down stomach (cUDS) hernias are a subgroup of large hiatal hernias characterized by high risk of life-threatening complications and technically challenging surgical repair including complex mediastinal dissection. In a prospective, comparative clinical study, we evaluated intra- and postoperative outcomes, quality of life and symptomatic recurrence rates in patients with cUDS undergoing robot-assisted, as compared to standard laparoscopic repair (the RATHER-study). METHODS: All patients with cUDS herniation requiring elective surgery in our institution between July 2015 and June 2019 were evaluated. Patients undergoing primary open surgery or additional associated procedures were not considered. Primary endpoints were intra- and postoperative complications, 30-day morbidity, and mortality. During the 8-53 months follow-up period, patients were contacted by telephone to assess symptoms associated to recurrence, whereas quality of life was evaluated utilizing the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) questionnaire. RESULTS: A total of 55 patients were included. 36 operations were performed with robot-assisted (Rob-G), and 19 with standard laparoscopic (Lap-G) technique. Patients characteristics were similar in both groups. Median operation time was 232 min. (IQR: 145-420) in robot-assisted vs. 163 min. (IQR:112-280) in laparoscopic surgery (p < 0.001). Intraoperative complications occurred in 5/36 (12.5%) cases in the Rob-G group and in 5/19 (26%) cases in the Lap-G group (p = 0.28). No conversion was necessary in either group. Minor postoperative complications occurred in 13/36 (36%) Rob-G patients and 4/19 (21%) Lap-G patients (p = 0.36). Mortality or major complications did not occur in either group. Two asymptomatic recurrences were observed in the Rob-G group only. No patient required revision surgery. Finally, all patients expressed satisfaction for treatment outcome, as indicated by similar GERD-HRQL scores. CONCLUSION: While robot-assisted surgery provides additional precision, enhanced visualization, and greater feasibility in cUDS hiatal hernia repair, its clinical outcome is at least equal to that obtained by standard laparoscopic surgery.

Performance of the ESC 0/2h-algorithm using high-sensitivity cardiac troponin I in the early diagnosis of myocardial infarction.

The 2020 guidelines of the European Society of Cardiology (ESC) recommend a novel ESC 0/2h-algorithm as the preferred alternative to the ESC 0/1h-algorithm in the early triage for rule-out and/or rule-in of Non-ST-segment-elevation myocardial infarction (NSTEMI). The aim was to prospectively validate the performance of the ESC 0/2h-algorithm using the high-sensitivity cardiac troponin I (hs-cTnI) assay (ARCHITECT) in an international, multicenter diagnostic study enrolling patients presenting with acute chest discomfort to the emergency department.

Early Rule-Out Strategies in the Emergency Department Utilizing High-Sensitivity Cardiac Troponin Assays.

BACKGROUND: Over the past decade, intense collaboration between academic investigators and the diagnostic industry have allowed the integration of high-sensitivity cardiac troponin (hs-cTn) assays into clinical practice worldwide. The hs-cTn assays, with their increased diagnostic accuracy for acute myocardial infarction (AMI), have facilitated the maturation of early rule-out strategies. The first iteration was complex and required the combination of a biomarker panel, the electrocardiogram, and a clinical risk score and allowed the safe rule-out of AMI in only 10% of patients with acute chest pain. In contrast, the latest iterations, including the European Society of Cardiology (ESC) 0/1-h algorithm, are simple. They are based on hs-cTn concentrations only and allow the safe rule-out or rule-in of AMI in up to 75% of patients. CONTENT: The purposes of this minireview are (a) to describe the best validated hs-cTn-based strategies for early rule-out of AMI, (b) to discuss the advantages and limitations of the different strategies, (c) to identify patient subgroups requiring particular attention, (d) to recognize challenges for widespread clinical implementation, and (e) to provide guidance on strategies for their safe and effective clinical implementation. SUMMARY: Physicians and institutions may choose among several well-validated rule-out algorithms. The ESC 0/1-h algorithm for hs-cTnT or hs-cTnI seems to be the most attractive option today. It best balances safety and efficacy, and it has been derived and validated for all currently available hs-cTnT/I assays, facilitating widespread clinical implementation.

Using High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia in Symptomatic Patients: A Cohort Study.

Background: The optimal noninvasive method for surveillance in symptomatic patients with stable coronary artery disease (CAD) is unknown. Objective: To apply a novel approach using very low concentrations of high-sensitivity cardiac troponin I (hs-cTnI) for exclusion of inducible myocardial ischemia in symptomatic patients with CAD. Design: Prospective diagnostic cohort study. (ClinicalTrials.gov: NCT01838148). Setting: University hospital. Patients: 1896 consecutive patients with CAD referred with symptoms possibly related to inducible myocardial ischemia. Measurements: Presence of inducible myocardial ischemia was adjudicated using myocardial perfusion imaging with single-photon emission computed tomography, as well as coronary angiography and fractional flow reserve measurements where available. Staff blinded to adjudication measured circulating hs-cTn concentrations. An hs-cTnI cutoff of 2.5 ng/L, derived previously in mostly asymptomatic patients with CAD, was assessed. Predefined target performance criteria were at least 90% negative predictive value (NPV) and at least 90% sensitivity for exclusion of inducible myocardial ischemia. Sensitivity analyses were based on measurements with an hs-cTnT assay and an alternative hs-cTnI assay with even higher analytic sensitivity (limit of detection, 0.1 ng/L). Results: Overall, 865 patients (46%) had inducible myocardial ischemia. The hs-cTnI cutoff of 2.5 ng/L provided an NPV of 70% (95% CI, 64% to 75%) and a sensitivity of 90% (CI, 88% to 92%) for exclusion of inducible myocardial ischemia. No hs-cTnI cutoff reached both performance characteristics predefined as targets. Similarly, using the alternative assays for hs-cTnI or hs-cTnT, no cutoff achieved the target performance: hs-cTnT concentrations less than 5 ng/L yielded an NPV of 66% (CI, 59% to 72%), and hs-cTnI concentrations less than 2 ng/L yielded an NPV of 68% (CI, 62% to 74%). Limitation: Data were generated in a large single-center diagnostic study using central adjudication. Conclusion: In symptomatic patients with CAD, very low hs-cTn concentrations, including hs-cTnI concentrations less than 2.5 ng/L, do not generally allow users to safely exclude inducible myocardial ischemia. Primary Funding Source: European Union, Swiss National Science Foundation, Kommission für Technologie und Innovation (Innosuisse), Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel, University Hospital Basel, Roche, Abbott, and Singulex.

B-Type Natriuretic Peptides and Cardiac Troponins for Diagnosis and Risk-Stratification of Syncope.

BACKGROUND: The utility of BNP (B-type natriuretic peptide), NT-proBNP (N-terminal proBNP), and hs-cTn (high-sensitivity cardiac troponin) 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 those of clinical assessments, in patients >45-years old presenting with syncope to the emergency department 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 2 physicians based on all information available including cardiac work-up and 1-year follow-up, was the diagnostic end point. EGSYS (Evaluation of Guidelines in Syncope Study), a syncope-specific diagnostic score, served as the diagnostic comparator. Death and major adverse cardiac events at 30 and 720 days were the prognostic end points. Major adverse cardiac events 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. ROSE (Risk Stratification of Syncope in the Emergency Department), OESIL (Osservatorio Epidemiologico della Sincope nel Lazio), SFSR (San Fransisco Syncope Rule), and CSRS (Canadian Syncope Risk Score) 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 versus other causes (P<0.01). The diagnostic accuracy for cardiac syncope, as quantified by the area under the curve, was 0.77 to 0.78 (95% CI, 0.74-0.81) for all 4 biomarkers, and superior to EGSYS (area under the curve, 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 area under the curve of 0.81 (P<0.01). BNP, NT-proBNP, hs-cTnT, and hs-cTnI cut-offs, achieving predefined thresholds for sensitivity and specificity (95%), allowed for rule-in or rule-out of ≈30% of all patients. A total of 450 major adverse cardiac events occurred during follow-up. The prognostic accuracy of BNP, NT-proBNP, hs-cTnI, and hs-cTnT for major adverse cardiac events was moderate-to-good (area under the curve, 0.75-0.79), superior to ROSE, OESIL, and SFSR, and inferior to CSRS. CONCLUSIONS: BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations provide useful diagnostic and prognostic information in emergency department patients with syncope. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT01548352.

Incidence, characteristics, determinants, and prognostic impact of recurrent syncope.

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

Echocardiographic and Clinical Follow-up After Aortic Valve Neocuspidization Using Autologous Pericardium.

INTRODUCTION: Mid-term data from a single centre showed the safety and durability of aortic valve neocuspidization using autologous pericardium (OZAKI procedure). Since validation data from other centres are missing, aim of this study was to analyze echocardiographic and clinical results of our first patients that were operated with the OZAKI technique. METHODS: Thirty-five patients (24 males, median (IQR) age 72.0 (59.0, 76.0) years) with aortic stenosis (AS; n = 10), aortic insufficiency (AR; n = 13) or a combination of both (AS/AR; n = 12), underwent aortic valve neocuspidization in our institution between September 2015 and May 2017. Echocardiographic follow-up was performed using a standardized examination protocol. RESULTS: Clinical follow-up was completed in 97% of the patients. Median (IQR) follow-up time was 645 (430, 813) days. Mortality rate was 9% (n = 1: aspiration pneumonia; n = 1: unknown; n = 1: anaphylactic shock), and the reoperation rate was 3% (n = 1: endocarditis). No pacemaker implantation was necessary after isolated OZAKI procedures. Echocardiographic follow-up was performed in 83% of the patients (n = 29; median (IQR) time 664 (497, 815) days). Median (IQR) mean and peak gradients were 6 (5,9) mmHg and 12 (8, 17) mmHg. Moderate aortic regurgitation was seen in 2 patients (7%). No severe aortic regurgitation or moderate or severe aortic stenosis occurred within the follow-up period. CONCLUSIONS: The OZAKI procedure is reliable and reoperation due to structural valve deterioration nil within a median 645 days follow-up period. The low rate of moderate aortic regurgitation will be surveilled very closely. Further studies are required to evaluate the significance of this procedure in aortic valve surgery. CLINICAL REGISTRATION NUMBER: ClinicalTrials.gov (ID NCT03677804).

Impact of Modified Frozen Elephant Trunk Procedure on Downstream Aorta Remodeling in Acute Aortic Dissection: CT Scan Follow-Up.

OBJECTIVES: The aim was to evaluate the impact of a modified frozen elephant trunk procedure (mFET) on remodeling of the downstream aorta following acute aortic dissections. METHODS: Over a period of 8 years, 205 patients (mean age 62.6 ± 12.6 years) underwent a mFET (n = 69, 33.7%) or isolated ascending aorta replacement (n = 136, 66.3%) (iAoA). Aortic diameter was assessed at the aortic arch (AoA), at the mid of the thoracic aorta (mThA), at the thoracoabdominal transition (ThAbd) and at the celiac trunk level (AbdA). RESULTS: Mean follow-up was 3.3 ± 2.6 years. In-hospital mortality was 14% (n = 28), 7% in mFET and 17% in the iAoA group (p = 0.08). At the end of the follow-up, overall survival was 84% (95% CI 70-92%) and 75% (65-82%) and freedom from aorta-related reoperation was 100% and 95% (88-98%) for mFET and iAoA, respectively. At iAoA, the average difference in diameter change per year between mFET and iAoA was for total lumen 0 mm (- 0.95 to 0.94 mm, p = 0.99), and for true lumen, it was 1.23 mm (- 0.09 to 2.55 mm) per year, p = 0.067. False lumen demonstrated a decrease in diameter in mFET as compared to iAoA by - 1.43 mm (- 2.75 to - 0.11 mm), p = 0.034. In mFET, at the aortic arch level the total lumen diameter decreased from 30.7 ± 4.8 mm to 30.1 ± 2.5 mm (Δr + 2.90 ± 3.64 mm) and in iAoA it increased from 31.8 ± 4.9 to 34.6 ± 5.9 mm (Δr + 2.88 ± 4.18 mm). CONCLUSION: The mFET procedure provides satisfactory clinical outcome at short term and mid-term and has a positive impact on aorta remodeling, especially at the level of the aortic arch.

Microplegia versus Cardioplexol® in Coronary Artery Bypass Surgery with Minimal Extracorporeal Circulation: Comparison of Two Cardioplegia Concepts.

BACKGROUND: The aim of this study is to compare the combined use of the Myocardial Protection System and our microplegia (Basel Microplegia Protocol) with Cardioplexol® in coronary artery bypass grafting using the minimal extracorporeal circulation. METHODS: The analysis focused on propensity score matched pairs of patients in whom microplegia or Cardioplexol® was used. Primary efficacy endpoints were high-sensitivity cardiac troponin-T on postoperative day 1 and peak values during hospitalization. Furthermore, we assessed creatine kinase and creatinine kinase-myocardial type, as well as safety endpoints. RESULTS: A total of 56 patients who received microplegia and 155 patients who received Cardioplexol® were included. The use of the microplegia was associated with significantly lower geometric mean (confidence interval) peak values of high-sensitivity cardiac troponin-T (233 ng/L [194-280 ng/L] vs. 362 ng/L [315-416 ng/L]; p = 0.001), creatinine kinase (539 U/L [458-633 U/L] vs. 719 U/L [645-801 U/L]; p = 0.011), and creatinine kinase-myocardial type (13.8 µg/L [9.6-19.9 µg/L] vs. 21.6 µg/L [18.9-24.6 µg/L]; p = 0.026), and a shorter length of stay on the intensive care unit (1.5 days [1.2-1.8 days] vs. 1.9 days [1.7-2.1 days]; p = 0.011). Major adverse cardiac and cerebrovascular events occurred with roughly equal frequency (1.8 vs. 5.2%; p = 0.331). CONCLUSIONS: The use of the Basel Microplegia Protocol was associated with lower peak values of high-sensitivity cardiac troponin-T, creatinine kinase, and creatinine kinase-myocardial type and with a shorter length of stay on the intensive care unit, as compared with the use of Cardioplexol® in isolated coronary artery bypass surgery using minimal extracorporeal circulation.

Analysis of Myocardial Ischemia Parameters after Coronary Artery Bypass Grafting with Minimal Extracorporeal Circulation and a Novel Microplegia versus Off-Pump Coronary Artery Bypass Grafting.

BACKGROUND: To compare the performance of our institutionally refined microplegia protocol in conjunction with minimal extracorporeal circulation system (MiECC) with off-pump coronary artery bypass grafting (OPCAB). METHODS: We conducted a single center study including patients undergoing isolated CABG surgery performed either off-pump or on-pump using our refined microplegia protocol in conjunction with MiECC. We used propensity modelling to calculate the inverse probability of treatment weights (IPTW). Primary endpoints were peak values of high-sensitivity cardiac troponin T (hs-cTnT) during hospitalization, and respective first values on the first postoperative day. Endpoint analysis was adjusted for intraoperative variables. RESULTS: After IPTW, we could include 278 patients into our analyses, 153 of which had received OPCAB and 125 of which had received microplegia. Standardized differences indicated that treatment groups were comparable after IPTW. The multivariable quantile regression yielded a nonsignificant median increase of first hs-cTnT by 39 ng/L (95% CI -8 to 87 ng/L, p = 0.11), and of peak hs-cTnT by 35 ng/L (CI -13 to 84, p = 0.11), and of peak hs-cTnT by 35 ng/L (CI -13 to 84, p = 0.11), and of peak hs-cTnT by 35 ng/L (CI -13 to 84, p = 0.11), and of peak hs-cTnT by 35 ng/L (CI -13 to 84. CONCLUSION: The use of our institutionally refined microplegia in conjunction with MiECC was associated with similar results with regard to ischemic injury, expressed in hs-cTnT compared to OPCAB. MACCE was seen equally frequent. ICU discharge was earlier if microplegia was used.