Aiming towards evidence based interpretation of cardiac biomarkers in patients presenting with chest pain : The WESTCOR study

Bakgrunn: Ca 10% av alle pasientar i akuttmottak blir innlagt med brystsmerter og spørsmål om akutt koronarsyndrom (AKS), men under ¼ av pasientane har AKS. Metode:WESTCOR studien er ein prospektiv observasjonsstudie som inkluderer pasientar i akuttmottak med mistanke om AKS. Ein har brukt ulike vinklingar for å identifisera kardielle endepunkt, og samanliknar endepunkta med anbefalingar frå European Society of Cardiology (ESC): 1) Utvikla 0/1 times algoritmar for eit nytt høg sensitivt troponin I assay frå Singulex (hs-cTnISgx), 2) Samanlikning av ESC 0/3 timars algoritmar (2015) og High-Sensitive Troponin i Evaluering av patientar med Akutt Koronar Syndrom (high-STEACS) algoritmar kombinert med AKS kriteria frå ESC eller elleve ulike risikoskårar, 3) Utvikling av nye hs-cTnT og hs-cTnI algoritmar som nyttar lave slutningsgrenser både for nullprøven og deltaprøvane (1 og 3 timar). Resultat: 1) Samanlikna med andre troponinmetodar, hadde nullprøven frå hs-cTnI(Sgx) signifikant høgare areal under kurven (AUC) (0.95 versus 0.91 hs-cTnTESC, P<0.001 og 0.93 for hs-cTnIESC(Abbott), P=0.004, Delong test) for å utelukka non-ST elevasjons myokardial infarkt (NSTEMI). 0/1 timars hs-cTnI(Sgx) algoritmane plasserte 92% av pasientane i enten låg eller høgrisikogruppa for NSTEMI, medan hs-cTnTESC og hs-cTnIESC(Abbott) plasserte ≤78%. 0/1 times hs-cTnI(Sgx) algoritmen gav ingen langtids prognostisk information (total mortalitet og MI). 2) Dei to 0/3 timar algoritmane kombinert med AKS kriteria plasserte 3,8-4,9% av pasientane som fekk det kombinerte endepunkt MI, total mortalitet, og revaskularisering innan 30 dagar i lågrisikogruppa. Kombinasjon med HEART score ≤3 reduserte endepunkta i lågrisikogruppa til 2.2-2.7%. 3) Den nye hs-TnT 0/1 times algoritmen hadde ein sensitivitet for det kombinerte endepunktet NSTEMI eller ustabil angina pectoris (UAP) under opphald på 95% versus 63% for ESC algoritmen (P<0.001) Evna til å senda ut pasientar med den nye hs-TnT 0/1 algorithm vart signifikant redusert, 21% versus 82 % (P<0.001). Algoritmen frå hs-cTnI(Abbott) hadde sensitiv på 87% og spesifisitet 45%. Konklusjon: Dette arbeidet viser nye måtar å vurdera og forbetra diagnostikken av brystsmerterpasientar i akuttmottak.Background: Chest pain patients admitted to the emergency department (ED) with possible acute coronary syndrome (ACS) encompasses about 10% of the ED population, only a relatively small proportion have ACS. Method: The WESTCOR study is a prospective observational study, including patients with ACS symptoms. Different approaches for predicting major adverse cardiovascular events (MACE) are investigated and compared to European Society of Cardiology (ESC) recommendations: 1) novel 0/1 hour algorithms using a high sensitivity troponin I assay from Singulex (hs-cTnISgx) with measurable results in >99% of healthy persons. 2) 0/3 hour ESC (2015) and the High-Sensitivity Troponin in the Evaluation of patients with Acute Coronary Syndrome (high-STEACS) algorithms combined with the ACS criteria from ESC or eleven different risk scores: 3) novel hs-cTnT and hs-cTnI rule-out algorithms designed with low baseline/low (1-3) hour delta values. Results: 1) The hs-cTnI(Sgx) baseline value for rule-out of non-ST elevation myocardial infarction (NSTEMI) had significant higher Area under the Receiver Operating Characteristic (AUROC) (0.95 vs. 0.91 for hs-cTnTESC, P<0.001 and 0.93 for hs-cTnI(Abbott), P=0.004, Delong test). The 0/1-hour hs-cTnI(Sgx) algorithms allocated 92% of patients to rule-in/rule-out, while comparator algorithms only ≤ 78%. The 0/1-hour hs-cTnI(Sgx) rule-out algorithm did not provide prognostic information for combined all-cause mortality and future nonfatal MI. 2) Combining 0/3- hour troponin algorithms from ESC or high-STEACS with the ACS criteria, ruled out 3.8-4.9% of patients who experienced MI, all-cause mortality, and revascularization within 30 days. A HEART score ≤3 reduced the event rate to 2.2-2.7%. 3) The clinical sensitivity for the hs-TnT 0/1-hour rule-out algorithm for predicting combined NSTEMI or unstable angina pectoris (UAP) during index hospitalization was 95% vs. 63% for the ESC algorithm (P<0.001)). The rule-out rate for the nove algorithm was significantly reduced, 21.0% vs 82% (P<0.001). The novel algorithm for hs-cTnI(Abbot) had slightly lower sensitivity 87% but better specificity 45%. Conclusion: This work suggests several novel approaches for improving the diagnostic workup of chest pain patients in the ED.Doktorgradsavhandlin

Prognostic significance of chronic myocardial injury diagnosed by three different cardiac troponin assays in patients admitted with suspected acute coronary syndrome

Objectives Chronic myocardial injury (CMI) is defined as stable concentrations of cardiac troponin T or I (cTnT or cTnI) above the assay-specific 99th percentile upper reference limit (URL) and signals poor outcome. The clinical implications of diagnosing CMI are unclear. We aimed to assess prevalence and association of CMI with long-term prognosis using three different high-sensitivity cTn (hs-cTn) assays. Methods A total of 1,292 hospitalized patients without acute myocardial injury had cTn concentrations quantified by hs-cTn assays by Roche Diagnostics, Abbott Diagnostics and Siemens Healthineers. The median follow-up time was 4.1 years. The prevalence of CMI and hazard ratios for mortality and cardiovascular (CV) events were calculated based on the URL provided by the manufacturers and compared to the prognostic accuracy when lower percentiles of cTn (97.5, 95 or 90), limit of detection or the estimated bioequivalent concentrations between assays were used as cutoff values. Results There was no major difference in prognostic accuracy between cTnT and cTnI analyzed as continuous variables. The correlation between cTnT and cTnI was high (r=0.724–0.785), but the cTnT assay diagnosed 3.9–4.5 times more patients with having CMI based on the sex-specific URLs (TnT, n=207; TnI Abbott, n=46, TnI Siemens, n=53) and had higher clinical sensitivity and AUC at the URL. Conclusions The prevalence of CMI is highly assay-dependent. cTnT and cTnI have similar prognostic accuracy for mortality or CV events when measured as continuous variables. However, a CMI diagnosis according to cTnT has higher prognostic accuracy compared to a CMI diagnosis according to cTnI.publishedVersio

Predictors of long-term symptom burden and quality of life in patients hospitalised with chest pain: a prospective observational study

Objective: To describe the magnitude and predictors of symptom burden (SB) and quality of life (QoL) 3 months after hospital admission for acute chest pain. Design: Prospective observational study. Setting: Single centre, outpatient follow-up. Participants: 1506 patients. Outcomes: Scores reported for general health (RAND-12), angina-related health (Seattle Angina Questionnaire 7 (SAQ-7)) and dyspnoea (Rose Dyspnea Scale) 3 months after hospital admission for chest pain. Methods: A total of 1506 patients received questionnaires assessing general health (RAND-12), angina-related health (SAQ-7) and dyspnoea (Rose Dyspnea Scale) 3 months after discharge. Univariable and multivariable regression models identified predictors of SB and QoL scores. A mediator analysis identified factors mediating the effect of an unstable angina pectoris (UAP) diagnosis. Results: 774 (52%) responded. Discharge diagnoses were non-ST elevation myocardial infarction (NSTEMI) (14.2%), UAP (17.1%), non-coronary cardiac disease (6.6%), non-cardiac disease (6.3%) and non-cardiac chest pain (NCCP) (55.6%). NSTEMI had the most favourable, and UAP patients the least favourable SAQ-7 scores (median SAQ7-summary; 88 vs 75, p±10%) of an UAP diagnosis for all SAQ-7 and RAND-12 outcomes. Conclusions: Patients with NSTEMI reported the most favourable outcome 3 months after hospitalisation for chest pain. Patients with other diseases, in particular UAP patients, reported lower scores. Revascularised NSTEMI and UAP patients reported higher QoL scores compared with patients receiving conservative treatment. Revascularisation mediated all outcomes in UAP patients.publishedVersio

Growth Differentiation Factor 15: A Prognostic Marker in Patients with Acute Chest Pain without Acute Myocardial Infarction

Background Acute chest pain is associated with an increased risk of death and cardiovascular events even when acute myocardial infarction (AMI) has been excluded. Growth differentiation factor-15 (GDF-15) is a strong prognostic marker in patients with acute chest pain and AMI, but the prognostic value in patients without AMI is uncertain. This study sought to investigate the ability of GDF-15 to predict long-term prognosis in patients presenting with acute chest pain without AMI. Methods In total, 1320 patients admitted with acute chest pain without AMI were followed for a median of 1523 days (range: 4 to 2208 days). The primary end point was all-cause mortality. Secondary end points included cardiovascular (CV) death, future AMI, heart failure hospitalization, and new-onset atrial fibrillation (AF). Results Higher concentrations of GDF-15 were associated with increased risk of death from all causes (median concentration in non-survivors vs survivors: 2124 pg/mL vs 852 pg/mL, P < 0.001), and all secondary end points. By multivariable Cox regression, GDF-15 concentration ≥4th quartile (compared to <4th quartile) remained an independent predictor of all-cause death (adjusted hazard ratio (HR): 2.75; 95% CI, 1.69–4.45, P < 0.001), CV death (adjusted HR: 3.74; 95% CI, 1.31–10.63, P = 0.013), and heart failure hospitalization (adjusted HR: 2.60; 95% CI, 1.11–6.06, P = 0.027). Adding GDF-15 to a model consisting of established risk factors and high-sensitivity cardiac troponin T (hs-cTnT) led to a significant increase in C-statistics for prediction of all-cause mortality. Conclusions Higher concentrations of GDF-15 were associated with increased risk of mortality from all causes and risk of future CV events.publishedVersio

Aiming towards evidence based interpretation of cardiac biomarkers in patients presenting with chest pain : The WESTCOR study

Bakgrunn: Ca 10% av alle pasientar i akuttmottak blir innlagt med brystsmerter og spørsmål om akutt koronarsyndrom (AKS), men under ¼ av pasientane har AKS. Metode:WESTCOR studien er ein prospektiv observasjonsstudie som inkluderer pasientar i akuttmottak med mistanke om AKS. Ein har brukt ulike vinklingar for å identifisera kardielle endepunkt, og samanliknar endepunkta med anbefalingar frå European Society of Cardiology (ESC): 1) Utvikla 0/1 times algoritmar for eit nytt høg sensitivt troponin I assay frå Singulex (hs-cTnISgx), 2) Samanlikning av ESC 0/3 timars algoritmar (2015) og High-Sensitive Troponin i Evaluering av patientar med Akutt Koronar Syndrom (high-STEACS) algoritmar kombinert med AKS kriteria frå ESC eller elleve ulike risikoskårar, 3) Utvikling av nye hs-cTnT og hs-cTnI algoritmar som nyttar lave slutningsgrenser både for nullprøven og deltaprøvane (1 og 3 timar). Resultat: 1) Samanlikna med andre troponinmetodar, hadde nullprøven frå hs-cTnI(Sgx) signifikant høgare areal under kurven (AUC) (0.95 versus 0.91 hs-cTnTESC, P<0.001 og 0.93 for hs-cTnIESC(Abbott), P=0.004, Delong test) for å utelukka non-ST elevasjons myokardial infarkt (NSTEMI). 0/1 timars hs-cTnI(Sgx) algoritmane plasserte 92% av pasientane i enten låg eller høgrisikogruppa for NSTEMI, medan hs-cTnTESC og hs-cTnIESC(Abbott) plasserte ≤78%. 0/1 times hs-cTnI(Sgx) algoritmen gav ingen langtids prognostisk information (total mortalitet og MI). 2) Dei to 0/3 timar algoritmane kombinert med AKS kriteria plasserte 3,8-4,9% av pasientane som fekk det kombinerte endepunkt MI, total mortalitet, og revaskularisering innan 30 dagar i lågrisikogruppa. Kombinasjon med HEART score ≤3 reduserte endepunkta i lågrisikogruppa til 2.2-2.7%. 3) Den nye hs-TnT 0/1 times algoritmen hadde ein sensitivitet for det kombinerte endepunktet NSTEMI eller ustabil angina pectoris (UAP) under opphald på 95% versus 63% for ESC algoritmen (P<0.001) Evna til å senda ut pasientar med den nye hs-TnT 0/1 algorithm vart signifikant redusert, 21% versus 82 % (P<0.001). Algoritmen frå hs-cTnI(Abbott) hadde sensitiv på 87% og spesifisitet 45%. Konklusjon: Dette arbeidet viser nye måtar å vurdera og forbetra diagnostikken av brystsmerterpasientar i akuttmottak

Association between symptoms and risk of non-ST segment elevation myocardial infarction according to age and sex in patients admitted to the emergency department with suspected acute coronary syndrome: a single-centre retrospective cohort study

Objectives Evaluate the association between symptoms and risk of non-ST segment elevation myocardial infarction (NSTEMI) in patients admitted to an emergency department with suspected acute coronary syndrome based on sex and age. Design Post hoc analysis of a prospective observational study conducted between September 2015 and May 2019. Setting University hospital in Norway. Participants 1506 participants >18 years of age (39.6% women and 31.0% 70 years of age or older). Findings The OR for NSTEMI was 9.4 if pain radiated to both arms, 3.0 if exertional chest pain was present during the last week and 2.9 if pain occurred during activity. Men had significantly lower OR compared with women if pain was dependent of position, respiration or palpation (OR 0.17 vs 0.53, p value for interaction 0.047). Patients <70 years had higher predictive value than older patients if they reported exertional chest pain the last week (OR 4.08 vs 1.81, 95%, p value for interaction 0.025) and lower if pain radiated to the left arm (OR 0.73 vs 1.67, p value for interaction 0.045). Conclusions Chest pain with radiation to both arms, exertional chest pain during the last week and pain during activity had the strongest predictive value for NSTEMI. The differences in symptom presentation and risk of NSTEMI between sex and age groups were small. Trial registration number WESTCOR study ClinicalTrials.gov (NCT02620202)