Abstract

Monitoring of QTc interval is mandated in different clinical conditions. Nevertheless, intra-subject variability of QTc intervals reduces the clinical utility of QTc monitoring strategies. Since this variability is partly related to QT heart rate correction, 10 different heart rate corrections (Bazett, Fridericia, Dmitrienko, Framingham, Schlamowitz, Hodges, Ashman, Rautaharju, Sarma, and Rabkin) were applied to 452,440 ECG measurements made in 539 healthy volunteers (259 females, mean age 33.3 ± 8.4 years). For each correction formula, the short term (5-min time-points) and long-term (day-time hours) variability of rate corrected QT values (QTc) was investigated together with the comparisons of the QTc values with individually corrected QTcI values obtained by subject-specific modelling of the QT/RR relationship and hysteresis. The results showed that (a) both in terms of short-term and long-term QTc variability, Bazett correction led to QTc values that were more variable than the results of other corrections (p < 0.00001 for all), (b) the QTc variability by Fridericia and Framingham corrections were not systematically different from each other but were lower than the results of other corrections (p-value between 0.033 and < 0.00001), and (c) on average, Bazett QTc values departed from QTcI intervals more than the QTc values of other corrections. The study concludes that (a) previous suggestions that Bazett correction should no longer be used in clinical practice are fully justified, (b) replacing Bazett correction with Fridericia and/or Framingham corrections would improve clinical QTc monitoring, (c) heart rate stability is needed for valid QTc assessment, and (d) development of further QTc corrections for day-to-day use is not warranted.

Highlights

  • Monitoring of QTc interval is mandated in different clinical conditions

  • QTc prolongation assessment has been the topic of proposed scoring ­systems[8]

  • Since the variability and accuracy of QTc values by different formulas is likely influenced by the ECG-related characteristics of the investigated population, we have investigated these properties independently of any of the generic correction formulas

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Summary

Introduction

Monitoring of QTc interval is mandated in different clinical conditions. intra-subject variability of QTc intervals reduces the clinical utility of QTc monitoring strategies. QTc assessment and/or monitoring is mandated when administering drugs recognised to affect myocardial repolarisation and to potentially induce torsade de pointes t­achycardia[2]; when diagnosing the sources of syncopal and/or pre-syncopal ­episodes[3]; when considering the proarrhythmic consequences of treatment-induced electrolyte a­ bnormalities[4,5]; when screening relatives of patients with recognised repolarisation ­channelopathy[6] or of unexplained sudden death v­ ictims[7]; and in a further spectrum of other circumstances and conditions To support this practice, some healthcare providers stipulate corresponding guidelines. Electrocardiographic experience from clinical pharmacology studies suggests that intra-subject QTc variability is substantially reduced by systematic QT interval measurements and, and largely, by using

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