SUPPLEMENTARY DATA
Appendix A: Medication data at baseline and follow-up
Baseline ECG(≤3 days before) / Follow-up ECG
(between 2 ECGs)
Median total number of drugs (range) / 9 (0-20) / 13 (5-26)
Median number of QTc-prolonging drugs (range)
Number of patients with
0 QT-drugs
1 QT-drug
2 QT-drugs
3 QT-drugs
4 QT-drugs
5 QT-drugs
6 QT-drugs / 1 (0-4)
50 (28.1%)
69 (38.8%)
38 (21.3%)
15 (8.4%)
6 (3.4%) / 3 (1-6)
27 (15.2%)
58 (32.6%)
57 (32.0%)
27 (15.2%)
8 (4.5%)
1 (0.6%)
Median number of QTc-prolonging drugs list 1 CredibleMeds (range)
Number of patients with
0 QT-drugs
1 QT-drug
2 QT-drugs
3 QT-drugs / 0 (0-2)
135 (75.8%)
36 (20.2%)
7 (3.9%) / 1 (0-3)
25 (14.0%)
97 (54.5%)
51 (28.7%)
5 (2.8%)
Median number of QTc-prolonging drugs list 2 CredibleMeds (range)
Number of patients with
0 QT-drugs
1 QT-drug
2 QT-drugs / 0 (0-1)
150 (84.3%)
28 (15.7%) / 0 (0-2)
148 (83.1%)
29 (16.3%)
1 (0.6%)
Median number of QTc-prolonging drugs list 3 CredibleMeds (range)
Number of patients with
0 QT-drugs
1 QT-drug
2 QT-drugs
3 QT-drugs / 1 (0-2)
74 (41.6%)
71 (39.9%)
33 (18.3%) / 1 (0-3)
31 (17.4%)
85 (47.8%)
48 (27.0%)
14 (7.8%)
Mean number of QTc-prolonging drugs intravenously (IV) administered
Number of patients with ≥1 QTc-prolonging drugs IV / 0 (0-2)
22 (12.4%) / 0 (0-5)
40 (22.5%)
Mean number of QTc-prolonging drugs of which the metabolism is inhibited by a pharmacokinetic drug interaction
Number of patients with a pharmacokinetic interaction / 0 (0-1)
7 (3.9%) / 0 (0-3)
41 (23.0%)
Appendix B: Results of the spearman correlations (QTc as a continuous variable) and univariate logistic regressions (QTc a nominal variable: <450/470ms and ≥450/470ms), linking risk factors at baseline with the QTc-interval of the follow-up ECG
Spearman correlations / Univariate logistic regressionsBaseline risk factors / rho / p / OR [95% CI] / p
Age ≥65 years
Female sex / 0.120
-0.055 / 0.110
0.462 / 1.5 [0.6-3.7]
0.3 [0.1-0.8] / 0.367
0.013
Smoking
Alcohol abuse / -0.057
-0.004 / 0.447
0.961 / 0.3 [0.04-2.5]
3.3 [0.9-11.8] / 0.276
0.070
BMI ≥30 / -0.053 / 0.486 / 0.9 [0.3-2.8] / 0.829
(Ischemic) cardiomyopathy
Hypertension
Arrhythmia / 0.185
0.096
0.196 / 0.013
0.202
0.009 / 4.7 [1.8-11.8]
1.1 [0.5-2.6]
3.1 [1.3-7.5] / 0.001
0.818
0.011
Prolonged QTc (≥450(♂)/470(♀)ms) on a baseline ECG / 0.319 / <0.001 / 13.6 [5.2-35.9] / <0.001
Thyroid disturbances / 0.067 / 0.371 / 0.8 [0.2-3.8] / 0.803
Liver failure / 0.186 / 0.013 / 2.0 [0.4-10.6] / 0.403
Neurological disorders / 0.160 / 0.033 / 2.2 [0.7-6.6] / 0.171
Diabetes / 0.082 / 0.274 / 1.3 [0.5-3.4] / 0.557
Potassium ≤3.5mmol/L / 0.155 / 0.039 / 1.3 [0.4-4.1] / 0.686
Calcium <2.15mmol/L / 0.147 / 0.049 / 4.3 [1.5-12.3] / 0.006
CRP >5mg/L / 0.229 / 0.002 / 8.0 [1.1-61.4] / 0.044
Glomular filtration rate ≤30ml/min / 0.108 / 0.151 / 3.8 [1.4-10.1] / 0.008
≥1 QT-prolonging drug (list 1+2+3 CredibleMeds) at baseline / 0.179 / 0.017 / 5.5 [1.3-24.4] / 0.024
≥1 QT-prolonging drug IV* / 0.003 / 0.973 / 1.1 [0.4-2.6] / 0.905
≥1 QT-prolonging drug with a pharmacokinetic drug interaction (inhibiting the metabolism)* / -0.046 / 0.539 / 0.4 [0.1-3.4] /
0.423
IV = intravenous;OR = odds ratio; p = p-values (significance level ≤0.05); significant results are indicated in bold
* including started QTc-prolonging drug
Appendix C: ROC-curve and choosing a cut-off value for the preliminary RISQ-PATH score
Area under the curve: 0.718
Standard error: 0.048
p<0.001
95% CI: 0.624-811
Cut-off / ≥10 / ≥12 / ≥14
Number of patients (%) / 127 (71.3%) / 105 (59.0%) / 85 (47.8%)
Sensitivity / 96.2% / 88.5% / 69.2%
Specificity / 32.9% / 46.1% / 55.9%
Positive predictive value / 19.7% / 21.9% / 21.2%
Negative predictive value / 98.0% / 95.9% / 91.4%