Using the clinical chemistry score in the emergency department to detect adverse cardiac events: a diagnostic accuracy study

Peter A. Kavsak; Joshua O. Cerasuolo; Dennis T. Ko; Jinhui Ma; Jonathan Sherbino; Shawn E. Mondoux; Natasha Clayton; Stephen A. Hill; Matthew McQueen; Lauren E. Griffith; Shamir R. Mehta; Richard Perez; Hsien Seow; P.J. Devereaux; Andrew Worster

doi:10.9778/cmajo.20200047

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Figure 1:
Flow diagram of the 2 different ED cohorts in this study. ACS = acute coronary syndrome, CCS = clinical chemistry score, hs-cTnI = high-sensitivity cardiac troponin I, hs-cTnT = high-sensitivity cardiac troponin T, ED = emergency department, EDP = emergency department physician, eGFR = estimated glomerular filtration rate, MACE = major adverse cardiac event, NSTEMI = non-ST-segment elevation myocardial infarction, OHIP = Ontario Health Insurance Plan, RPDB = Registered Persons Database, STEMI = ST-segment elevation myocardial infarction.

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Table 1:

Characteristics of the 2 study cohorts

Characteristic	No. (%) of patients^*
Characteristic	Cohort 1 n = 1058	Cohort 2 n = 5974
Age, yr, mean ± SD	67 ± 17	68 ± 17
Female sex	558 (52.7)	3025 (50.6)
Hypertension	744 (70.3)	4045 (67.7)
Diabetes mellitus	312 (29.4)	1961 (32.8)
History of myocardial infarction	378 (35.7)	674 (11.3)
History of PCI or CABG	236 (22.3)	453 (7.6)
History of peripheral vascular disease	75 (7.1)	742 (12.4)
Glucose concentration, mmol/L, mean ± SD	7.4 ± 3.6	7.6 ± 4.4
eGFR, mL/min per 1.73 m², mean ± SD	72 ± 27	69 ± 27
hs-cTnI concentration at presentation < 99th percentile cut-off^†	842 (79.6)	4698 (78.6)
30-day MACE	205 (19.4)	871(14.6)

Note: CABG = coronary artery bypass grafting, eGFR = estimated glomerular filtration rate, hs-cTNI = high-sensitivity cardiac troponin I, MACE = major adverse cardiac event, PCI = percutaneous coronary intervention, SD = standard deviation.
↵* Unless indicated otherwise.
↵† 99th percentile upper reference limit is 11 ng/L for Ortho hs-cTnI assay and 26 ng/L for Abbott hs-cTnI assay.

Table 2:

Performance of the clinical chemistry score versus hs-cTnI concentration (measured using the Ortho Vitros 3600 hs-cTnI assay) alone for identifying risk for 30-day MACE

Score cut-off	Patients with at least 1 MACE within 30 d	Patients with no MACE within 30 d
CCS ≥ 1, no. of patients	204	744
CCS < 1, no. of patients	1^*	109
Sensitivity, % (95% CI)	99.5 (97.3–99.9)
Negative predictive value, % (95% CI)	99.1 (93.9–99.9)
Negative likelihood ratio (95% CI)	0.04 (0.01–0.27)
Specificity, % (95% CI)	12.8 (10.6–15.2)
Positive predictive value, % (95% CI)	21.5 (21.1–21.9)
Positive likelihood ratio (95% CI)	1.14 (1.11–1.17)
hs-cTnI ≥ 1 ng/L, no. of patients	187	519
hs-cTnI < 1 ng/L, no. of patients	18	334
Sensitivity, % (95% CI)	91.2 (86.5–94.7)
Negative predictive value, % (95% CI)	94.9 (92.2–96.7)
Negative likelihood ratio (95% CI)	0.22 (0.14–0.35)
Specificity, % (95% CI)	39.2 (35.9–42.5)
Positive predictive value, % (95% CI)	26.5 (25.2–27.8)
Positive likelihood ratio (95% CI)	1.50 (1.40–1.61)
hs-cTnI ≥ 5 ng/L, no. of patients	152	183
hs-cTnI < 5 ng/L, no. of patients	53	669
Sensitivity, % (95% CI)	74.2 (67.6–80.0)
Negative predictive value, % (95% CI)	92.7 (90.9–94.1)
Negative likelihood ratio (95% CI)	0.33 (0.26–0.42)
Specificity, % (95% CI)	78.5 (75.6–81.2)
Positive predictive value, % (95% CI)	45.4 (41.6–49.1)
Positive likelihood ratio (95% CI)	3.45 (2.97–4.02)
CCS = 5, no. of patients	58	19
CCS < 5, no. of patients	147	834
Specificity, % (95% CI)	97.8 (96.5–98.7)
Positive predictive value, % (95% CI)	75.3 (65.0–83.4)
Positive likelihood ratio (95% CI)	12.7 (7.74–20.8)
Sensitivity, % (95% CI)	28.3 (22.2–34.9)
Negative predictive value, % (95% CI)	85.0 (83.9–86.1)
Negative likelihood ratio (95% CI)	0.73 (0.67–0.80)
hs-cTnI > 11 ng/L, no. of patients	132	84
hs-cTnI ≤ 11 ng/L, no. of patients	73	768
Specificity, % (95% CI)	90.1 (87.9–92.0)
Positive predictive value, % (95% CI)	61.1 (55.6–66.4)
Positive likelihood ratio (95% CI)	6.5 (5.2–8.2)
Sensitivity, % (95% CI)	64.4 (57.4–70.9)
Negative predictive value, % (95% CI)	91.3 (89.7–92.7)
Negative likelihood ratio (95% CI)	0.39 (0.33–0.47)

Note: CCS = clinical chemistry score, CI = confidence interval, hs-cTNI = high-sensitivity cardiac troponin I, hs-cTNT = high-sensitivity cardiac troponin T, MACE = major adverse cardiac event.
↵* At presentation, this patient had the following values: hs-TnI < 1 ng/L with the Ortho assay, hs-cTnI < 2 ng/L with the Abbott assay and hs-cTnT < 3 ng/L with the Roche assay. The patient’s 30-day outcome was coronary artery bypass grafting.

Table 3:

Performance of the clinical chemistry score versus hs-cTnI concentration (measured using the Abbott Architect i2000 hs-cTnI assay) alone for identifying risk for 90-day MACE in cohort 2

Score cut-off	Patients with at least 1 MACE within 90 d	Patients with no MACE within 90 d
CCS ≥ 1, no. of patients	1092	4483
CCS < 1, no. of patients^*	8	391
Sensitivity, % (95% CI)	99.3 (98.6–99.7)
Negative predictive value, % (95% CI)	98.0 (96.1–99.0)
Negative likelihood ratio (95% CI)	0.09 (0.05–0.18)
Specificity, % (95% CI)	8.0 (7.3–8.8)
Positive predictive value, % (95% CI)	19.6 (19.4–19.7)
Positive likelihood ratio (95% CI)	1.08 (1.07–1.09)
hs-cTnI ≥ 5 ng/L, no. of patients	965	2635
hs-cTnI < 5 ng/L, no. of patients	135	2239
Sensitivity, % (95% CI)	87.7 (85.6–89.6)
Negative predictive value, % (95% CI)	94.3 (93.4–95.1)
Negative likelihood ratio (95% CI)	0.27 (0.23–0.31)
Specificity, % (95% CI)	45.9 (44.5–47.3)
Positive predictive value, % (95% CI)	26.8 (26.1–27.5)
Positive likelihood ratio (95% CI)	1.62 (1.57–1.68)
CCS = 5, no. of patients	420	488
CCS < 5, no. of patients	680	4386
Specificity, % (95% CI)	90.0 (89.1–90.8)
Positive predictive value, % (95% CI)	46.3 (43.5–49.1)
Positive likelihood ratio (95% CI)	3.81 (3.41–4.27)
Sensitivity, % (95% CI)	38.2 (35.3–41.1)
Negative predictive value, % (95% CI)	86.6 (86.0–87.1)
Negative likelihood ratio (95% CI)	0.69 (0.66–0.72)
hs-cTnI > 26 ng/L, no. of patients	567	709
hs-cTnI ≤ 26 ng/L, no. of patients	533	4165
Specificity, % (95% CI)	85.5 (84.4–86.4)
Positive predictive value, % (95% CI)	44.4 (42.2–46.6)
Positive likelihood ratio (95% CI)	3.54 (3.24–3.87)
Sensitivity, % (95% CI)	51.6 (48.5–54.5)
Negative predictive value, % (95% CI)	88.7 (88.0–89.3)
Negative likelihood ratio (95% CI)	0.57 (0.53–0.60)

Note: CCS = clinical chemistry score, CI = confidence interval, hs-cTnI = high-sensitivity cardiac troponin I, MACE = major adverse cardiac event.
↵* At 30 d, MACE occurred in ≤ 5 patients with a CCS < 1 and these results cannot be reported per ICES standard operating procedures where counts < 6 are suppressed for privacy reasons.