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Implications of Individual QT/RR Profiles-Part 1: Inaccuracies and Problems of Population-Specific QT/Heart Rate Corrections.

ABSTRACT: INTRODUCTION:Universal QT correction formulas are potentially problematic in corrected QT (QTc) interval comparisons at different heart rates. Instead of individual-specific corrections, population-specific corrections are occasionally used based on QT/RR data pooled from all study subjects. OBJECTIVE:To investigate the performance of individual-specific and population-specific corrections, a statistical modeling study was performed using QT/RR data of 523 healthy subjects. METHODS:In each subject, full drug-free QT/RR profiles were available, characterized using non-linear regression models. In each subject, 50 baseline QT/RR readings represented baseline data of standard QT studies. Using these data, linear and log-linear heart rate corrections were optimized for each subject and for different groups of ten and 50 subjects. These corrections were applied in random combinations of heart rate changes between - 10 and + 25 beats per minute (bpm) and known QTc interval changes between - 25 and + 25 ms. RESULTS:Both the subject-specific and population-specific corrections based on the 50 baseline QT/RR readings tended to underestimate/overestimate the QTc interval changes when heart rate was increasing/decreasing, respectively. The result spread was much wider with population-specific corrections, making the estimates of QTc interval changes practically unpredictable. CONCLUSION:Subject-specific heart rate corrections based on limited baseline drug-free data may lead to inconsistent results and, in the presence of underlying heart rate changes, may potentially underestimate or overestimate QTc interval changes. The population-specific corrections lead to results that are much more influenced by the combination of individual QT/RR patterns than by the actual QTc interval changes. Subject-specific heart rate corrections based on full profiles derived from drug-free baseline recordings with wide QT/RR distribution should be used when studying drugs expected to cause heart rate changes.

SUBMITTER: Malik M

PROVIDER: S-EPMC6426828 | biostudies-other | 2019 Mar

REPOSITORIES: biostudies-other

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Implications of Individual QT/RR Profiles-Part 1: Inaccuracies and Problems of Population-Specific QT/Heart Rate Corrections.

Malik Marek M Garnett Christine C Hnatkova Katerina K Vicente Jose J Johannesen Lars L Stockbridge Norman N

Drug safety 20190301 3

<h4>Introduction</h4>Universal QT correction formulas are potentially problematic in corrected QT (QTc) interval comparisons at different heart rates. Instead of individual-specific corrections, population-specific corrections are occasionally used based on QT/RR data pooled from all study subjects.<h4>Objective</h4>To investigate the performance of individual-specific and population-specific corrections, a statistical modeling study was performed using QT/RR data of 523 healthy subjects.<h4>Met ...[more]

PMID: 30255349

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Project description:INTRODUCTION: In this study, we investigated the outcomes for patients with intentional organophosphate poisoning. Previous reports indicate that in contrast to normal heart rate-corrected QT intervals (QTc), QTc prolongation might be indicative of a poor prognosis for patients exposed to organophosphates. METHODS: We analyzed the records of 118 patients who were referred to Chang Gung Memorial Hospital for management of organophosphate poisoning between 2000 and 2011. Patients were grouped according to their initial QTc interval, i.e., normal (<0.44 s) or prolonged (>0.44 s). Demographic, clinical, laboratory, and mortality data were obtained for analysis. RESULTS: The incidence of hypotension in patients with prolonged QTc intervals was higher than that in the patients with normal QTc intervals (P?=?0.019). By the end of the study, 18 of 118 (15.2%) patients had died, including 3 of 75 (4.0%) patients with normal QTc intervals and 15 of 43 (34.9%) patients with prolonged QTc intervals. Using multivariate-Cox-regression analysis, we found that hypotension (OR?=?10.930, 95% CI?=?2.961-40.345, P?=?0.000), respiratory failure (OR?=?4.867, 95% CI?=?1.062-22.301, P?=?0.042), coma (OR?=?3.482, 95% CI?=?1.184-10.238, P?=?0.023), and QTc prolongation (OR?=?7.459, 95% CI?=?2.053-27.099, P?=?0.002) were significant risk factors for mortality. Furthermore, it was revealed that non-survivors not only had longer QTc interval (503.00±41.56 versus 432.71±51.21 ms, P?=?0.002), but also suffered higher incidences of hypotension (83.3 versus 12.0%, P?=?0.000), shortness of breath (64 versus 94.4%, P?=?0.010), bronchorrhea (55 versus 94.4%, P?=?0.002), bronchospasm (50.0 versus 94.4%, P?=?0.000), respiratory failure (94.4 versus 43.0%, P?=?0.000) and coma (66.7 versus 11.0%, P?=?0.000) than survivors. Finally, Kaplan-Meier analysis demonstrated that cumulative mortality was higher among patients with prolonged QTc intervals than among those with normal QTc intervals (Log-rank test, Chi-square test?=?20.36, P<0.001). CONCLUSIONS: QTc interval helps predict mortality after intentional organophosphate poisoning.

Dataset Information

Implications of Individual QT/RR Profiles-Part 1: Inaccuracies and Problems of Population-Specific QT/Heart Rate Corrections.

Publications

Implications of Individual QT/RR Profiles-Part 1: Inaccuracies and Problems of Population-Specific QT/Heart Rate Corrections.

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