Supplementary material A.1. Information on derivation and validation of the GRACE score, HEART score and TIMI score

GRACE SCORE

The GRACE score was derived in 2003 with a multivariable logistic regression model using 11,389 patients, to stratify risk in patients with ACS at risk for death during hospitalization. (19) The final GRACE score includes Killip classification, systolic blood pressure, heart rate, age, creatinine level, cardiac arrest at admission, ST-segment deviation and elevated cardiac enzyme levels. “Killip class” for congestive heart failure is an increasing scale and contains 4 categories: [1] no signs of congestive heart failure, [2] rales and/or jugular venous distention, [3] pulmonary edema and [4] cardiogenic shock. (30) “Systolic blood pressure” and “heart rate” were measured in mmHg and beats/min respectively. “Age” included patients from 18 years old. “Creatinine level” was measured in mg/dL and blood was collected at admission. “Cardiac arrest at admission” was reported by the physician. “ST segment deviation” was scored if there was ST segment elevation or depression in anterior, inferior or lateral lead groups and was at least 1mm. “Elevated cardiac enzyme levels” were defined as positive troponin I or T, creatinine kinase-MB fraction or creatinine phosphokinase more than 2 times above the upper limit. (19, 31) The total score is calculated by the sum of the corresponding points for each variable. The total score ranges from 1 to 372 points. The GRACE score is calculated by a computer. A calculator can be found at The total GRACE score predicts the probability of in-hospital death.

TIMI SCORE

The TIMI score was derived in 2000 to stratify risk for patients with UA or NSTEMI at risk for the composite endpoint (including AMI, PCI, CABG, and death plus a combined endpoint of AMI, PCI, CABG and death) within 14 days. (22) Another TIMI score was developed for patients with STEMI, but will not be discussed here. (33) To calculate statistical significance of variables, univariate and multivariate logistic regression analysis were performed. The final model of the TIMI score incorporates age, risk factors, significant coronary stenosis, ST deviation, severe anginal symptoms, use of aspirin and elevated cardiac markers. Age is divided in above and below 65 years. Risk factors include family history of coronary artery disease, hypertension, hypercholesterolemia, diabetes or being a current smoker. Significant coronary stenosis is defined as prior coronary stenosis of ≥50%. ST deviation is scored when either transient ST elevation or persistent ST depression of ≥0.01mV is reported. Severe anginal symptoms were defined as more than or equal to 2 events in the last 24 hours. Use of aspirin must be at least for the last 7 days and elevated serum cardiac markers included creatinine kinase MB fraction and/or troponin level. (22) When a variable is present, the patient receives one point. This results in a score of 0 to 7. The TIMI score provides a percentage of risk for the combined endpoint at the corresponding total score.

HEART SCORE

The HEART score is derived in 2008 and stratifies risk for chest pain patients at the ED at risk for MACE (including AMI, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) and death) within 3 months. (18) HEART score consist of History, ECG, Age, Risk factors and Troponin. “History” is defined as physician’s opinion of suspiciousness for ACS from history taking (anamnesis). “ECG” is scored on ST depression, pacemaker rhythm, bundle branch block, repolarization abnormalities or normal ECG. “Age” includes every age above 18 years old. “Risk factors” incorporates history of cardiovascular disease (coronary revascularization, AMI, stroke or peripheral arterial disease), currently treated diabetes mellitus, diagnosed or treated hypertension, diagnosed hypercholesterolemia, current or recent (<3 months) smoker, family history of cardiovascular disease and obesity (body mass index >30). “Troponin” can consist of troponin I, troponin T or high sensitive Troponin and is scored on being below the normal limit, 1 to 3 times the normal limit, or more than 3 times above the normal limit. (18, 24). For each of the variables a score of 0, 1 or 2 points can be given, depending on the severity of the variable, which results in a score of 0 to 10 points. The total score corresponds to an advice for the physician: discharge, further diagnostic testing or (invasive) treatment.

Figure A.1. The GRACE, HEART and TIMI score

(a) The GRACE score

Source: Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, Van De Werf F, Avezum A, Goodman SG, Flather MD, Fox KA; Global Registry of Acute Coronary Events Investigators. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003;163(19):2345-53.

(b) the HEART score

Source: Six AJ., Backus, BE., Kelder JC. Chest pain in the emergency room: value of the HEART score. Netherlands Heart Journal. 2008; 16 (6): 191-6.

(c) the TIMI score

Source: Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, Mautner B, Corbalan R, Radley D, Braunwald E. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. 2000;284(7):835-42.

Table A.1. Characteristics of troponin kits and cut-offs ofhospitals in the HEART-Impact trial

Hospital / Type of troponin / Type of troponin T or I / Analyzer / Cut-off value
Hospital 1 / conventional / I / Siemens dimension vista / 45 ng/l
Hospital 2 / conventional / I / Beckman Coulter DxI / 40 ng/l
Hospital 3 / high sensitive / T / Roche modular / 14 ng/l
Hospital 4 / high sensitive / T / Roche Cobass / 10 ng/l
Hospital 5 / conventional / I / Beckman CoulterDxI / 60 ng/l
Hospital 6 / high sensitive / T / Roche Cobass / 14 ng/l
Hospital 7 / high sensitive / T / Roche Cobass / 30 ng/l + delta >8ng
Hospital 8 / high sensitive / T / Roche modular / 50 ng/l
Hospital 9 / high sensitive / T / Roche Cobass / 14 ng/l