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Heart-Rate-Corrected QT Interval Evolution in Premature Infants During the First Week of Life

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Abstract

Automated monitoring of the QT interval is increasingly common in a variety of clinical settings. A better understanding of how the heart-rate-corrected QT interval (QTc) evolves in early postnatal life is needed before its clinical utility in neonates can be determined. This study aimed to use real-time bedside monitoring as a tool to describe the QTc evolution of premature neonates during the first week of life. All neonates born at a gestation age (GA) of 31 weeks or later and admitted to the level 2 intensive care nursery of the authors’ institution between December 2012 and March 2013 were included in this study. The authors prospectively collected QTc values at 15-min intervals during the first week of life, then used two-way analysis of variance (ANOVA) to compare these data among three GA cohorts: 31 to <34 weeks (cohort A), 34 to <37 weeks (cohort B), and ≥37 weeks (cohort C). All the cohorts demonstrated a statistically significant decline in the 24-h average QTc during the first 3–4 days of life before reaching a stable baseline. No diurnal variation in the QTc was identified in any of the study patients. Marked variability and a progressive decline in the QTc of premature neonates occur during the first 3–4 days of life. Understanding this phenomenon is imperative when screening programs for the early detection of QT prolongation are considered.

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Abbreviations

ECG:

Electrocardiogram

GA:

Gestational age

ISCN:

Intermediate special care nursery

QTc:

Heart-rate-corrected QT interval

SIDS:

Sudden infant death syndrome

References

  1. Abu-Shaweesh JM (2004) Maturation of respiratory reflex responses in the fetus and neonate. Semin Neonatol 9:169–180. doi:10.1016/j.siny.2003.09.003

    Article  PubMed  Google Scholar 

  2. Ariagno RL, Mirmiran M, Adams MM, Saporito AG, Dubin AM, Baldwin RB (2003) Effect of position on sleep, heart rate variability, and QT interval in preterm infants at 1 and 3 months’ corrected age. Pediatrics 111:622–625

    Article  PubMed  Google Scholar 

  3. Barfield WD, Papile LA, Baley JE, Benitz W, Cummings J, Carlo WA, Kumar P et al (2012) Levels of neonatal care. Pediatrics 130:587–597. doi:10.1542/peds.2012-1999

    Article  Google Scholar 

  4. Batchvarov VN, Ghuran A, Smetana P, Hnatkova K, Harries M, Dilaveris P, Camm AJ, Malik M (2002) QT-RR relationship in healthy subjects exhibits substantial intersubject variability and high intrasubject stability. Am J Physiol Heart Circ Physiol 282:H2356–H2363. doi:10.1152/ajpheart.00860.2001

    Article  CAS  PubMed  Google Scholar 

  5. Benatar A, Ramet J, Decraene T, Vandenplas Y (2002) QT interval in normal infants during sleep with concurrent evaluation of QT correction formulae. Med Sci Monit 8:CR351–CR356

    PubMed  Google Scholar 

  6. Browne KF, Prystowsky E, Heger JJ, Chilson DA, Zipes DP (1983) Prolongation of the Q-T interval in man during sleep. Am J Cardiol 52:55–59

    Article  CAS  PubMed  Google Scholar 

  7. Charbit B, Samain E, Merckx P, Funck-Brentano C (2006) QT interval measurement: evaluation of automatic QTc measurement and new simple method to calculate and interpret corrected QT interval. Anesthesiology 104:255–260

    Article  PubMed  Google Scholar 

  8. Coceani F, Baragatti B (2012) Mechanisms for ductus arteriosus closure. Semin Perinatol 36:92–97. doi:10.1053/j.semperi.2011.09.018

    Article  PubMed  Google Scholar 

  9. Davey P (2002) How to correct the QT interval for the effects of heart rate in clinical studies. J Pharmacol Toxicol Methods 48:3–9. doi:10.1016/s1056-8719(03)00008-x

    Article  CAS  PubMed  Google Scholar 

  10. De Groote K, Suys B, Deleeck A, De Wolf D, Matthys D, Van Overmeire B (2003) How accurately can QT interval be measured in newborn infants? Eur J Pediatr 162:875–879. doi:10.1007/s00431-003-1321-9

    Article  PubMed  Google Scholar 

  11. Franz MR, Swerdlow CD, Liem LB, Schaefer J (1988) Cycle length dependence of human action potential duration in vivo: effects of single extrastimuli, sudden sustained rate acceleration and deceleration, and different steady-state frequencies. J Clin Invest 82:972–979. doi:10.1172/jci113706

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Gow RM, Ewald B, Lai L, Gardin L, Lougheed J (2009) The measurement of the QT and QTc on the neonatal and infant electrocardiogram: a comprehensive reliability assessment. Ann Noninvasive Electrocardiol 14:165–175. doi:10.1111/j.1542-474X.2009.00292.x

    Article  PubMed  Google Scholar 

  13. Harrington C, Kirjavainen T, Teng A, Sullivan CE (2001) Cardiovascular responses to three simple, provocative tests of autonomic activity in sleeping infants. J Appl Physiol 91:561–568

    CAS  PubMed  Google Scholar 

  14. Helfenbein ED, Ackerman MJ, Rautaharju PM, Zhou SH, Gregg RE, Lindauer JM, Miller D, Wang JJ, Kresge SS, Babaeizadeh S, Feild DQ, Michaud FP (2007) An algorithm for QT interval monitoring in neonatal intensive care units. J Electrocardiol 40(6 Suppl):S103–S110. doi:10.1016/j.jelectrocard.2007.06.019

    Article  PubMed  Google Scholar 

  15. Honda M, Komatsu R, Isobe T, Tabo M, Ishikawa T (2013) Involvement of the autonomic nervous system in diurnal variation of corrected QT intervals in common marmosets. J Pharmacol Sci 121:131–137

    Article  CAS  PubMed  Google Scholar 

  16. Kemper AR, Mahle WT, Martin GR, Cooley WC, Kumar P, Morrow WR, Kelm K, Pearson GD, Glidewell J, Grosse SD, Howell RR (2011) Strategies for implementing screening for critical congenital heart disease. Pediatrics 128:e1259–e1267. doi:10.1542/peds.2011-1317

    Article  PubMed  Google Scholar 

  17. Lau CP, Freedman AR, Fleming S, Malik M, Camm AJ, Ward DE (1988) Hysteresis of the ventricular paced QT interval in response to abrupt changes in pacing rate. Cardiovasc Res 22:67–72

    Article  CAS  PubMed  Google Scholar 

  18. Luo S, Michler K, Johnston P, Macfarlane PW (2004) A comparison of commonly used QT correction formulae: the effect of heart rate on the QTc of normal ECGs. J Electrocardiol 37(Suppl):81–90

    Article  PubMed  Google Scholar 

  19. Malik M, Farbom P, Batchvarov V, Hnatkova K, Camm AJ (2002) Relation between QT and RR intervals is highly individual among healthy subjects: implications for heart rate correction of the QT interval. Heart 87:220–228

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Malik M, Hnatkova K, Schmidt A, Smetana P (2008) Accurately measured and properly heart-rate-corrected QTc intervals show little daytime variability. Heart Rhythm 5:1424–1431. doi:10.1016/j.hrthm.2008.07.023

    Article  PubMed  Google Scholar 

  21. Malloy MH (2013) Prematurity and sudden infant death syndrome: United States 2005–2007. J Perinatol 33:470–475. doi:10.1038/jp.2012.158

    Article  CAS  PubMed  Google Scholar 

  22. Mirmiran M, Ariagno RL (2000) Influence of light in the NICU on the development of circadian rhythms in preterm infants. Semin Perinatol 24:247–257

    Article  CAS  PubMed  Google Scholar 

  23. Molnar J, Zhang F, Weiss J, Ehlert FA, Rosenthal JE (1996) Diurnal pattern of QTc interval: how long is prolonged? Possible relation to circadian triggers of cardiovascular events. J Am Coll Cardiol 27:76–83. doi:10.1016/0735-1097(95)00426-2

    Article  CAS  PubMed  Google Scholar 

  24. Murakawa Y, Inoue H, Nozaki A, Sugimoto T (1992) Role of sympathovagal interaction in diurnal variation of QT interval. Am J Cardiol 69:339–343

    Article  CAS  PubMed  Google Scholar 

  25. Neary MT, Mohun TJ, Breckenridge RA (2013) A mouse model to study the link between hypoxia, long QT interval, and sudden infant death syndrome. Dis Model Mech 6:503–507. doi:10.1242/dmm.010587

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Pelchovitz DJ, Ng J, Chicos AB, Bergner DW, Goldberger JJ (2012) QT-RR hysteresis is caused by differential autonomic states during exercise and recovery. Am J Physiol Heart Circ Physiol 302:H2567–H2573. doi:10.1152/ajpheart.00041.2012

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Pueyo E, Smetana P, Laguna P, Malik M (2003) Estimation of the QT/RR hysteresis lag. J Electrocardiol 36(Suppl):187–190

    Article  PubMed  Google Scholar 

  28. Schwartz PJ, Montemerlo M, Facchini M, Salice P, Rosti D, Poggio G, Giorgetti R (1982) The QT interval throughout the first 6 months of life: a prospective study. Circulation 66:496–501

    Article  CAS  PubMed  Google Scholar 

  29. Schwartz PJ, Stramba-Badiale M, Segantini A, Austoni P, Bosi G, Giorgetti R, Grancini F, Marni ED, Perticone F, Rosti D, Salice P (1998) Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med 338:1709–1714. doi:10.1056/nejm199806113382401

    Article  CAS  PubMed  Google Scholar 

  30. Schwartz PJ, Garson A Jr, Paul T, Stramba-Badiale M, Vetter VL, Wren C (2002) Guidelines for the interpretation of the neonatal electrocardiogram. A task force of the European Society of Cardiology. Eur Heart J 23:1329–1344

    Article  CAS  PubMed  Google Scholar 

  31. Seguela PE, Roze JC, Gournay V (2012) Evolution of the QT interval in premature infants: a preliminary study. Cardiol Young 22:430–435. doi:10.1017/s1047951111001958

    Article  PubMed  Google Scholar 

  32. Walsh SZ (1963) Electrocardiographic intervals during the first week of life. Am Heart J 66:36–41

    Article  CAS  PubMed  Google Scholar 

  33. Yap YG, Camm AJ (2003) Drug-induced QT prolongation and torsades de pointes. Heart 89:1363–1372

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Zhou SH, Helfenbein ED, Lindauer JM, Gregg RE, Feild DQ (2009) Philips QT interval measurement algorithms for diagnostic, ambulatory, and patient monitoring ECG applications. Ann Noninvasive Electrocardiol 14(Suppl 1):S3–S8. doi:10.1111/j.1542-474X.2008.00258.x

    Article  PubMed  Google Scholar 

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Conflict of interest

Michael J. Ackerman has received consulting fees/honoraria from Boston Scientific, Gilead Sciences, Medtronic, and St. Jude Medical and royalty income from Transgenomic. The remaining authors have neither financial relationships nor conflicts of interest relevant to this article to disclose.

Author information

Authors and Affiliations

  1. Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA

    Timothy J. B. Ulrich, Marc A. Ellsworth, William A. Carey, Brianna C. MacQueen, Christopher E. Colby & Michael J. Ackerman

  2. Division of Neonatal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Marc A. Ellsworth, William A. Carey & Christopher E. Colby

  3. Mayo Clinic School of Medicine, Mayo Clinic, Rochester, MN, USA

    Adeel S. Zubair

  4. Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN, USA

    Michael J. Ackerman

Authors
  1. Timothy J. B. Ulrich
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  2. Marc A. Ellsworth
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  3. William A. Carey
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  4. Adeel S. Zubair
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  5. Brianna C. MacQueen
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  6. Christopher E. Colby
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  7. Michael J. Ackerman
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Corresponding author

Correspondence to Marc A. Ellsworth.

Additional information

Dr. Timothy J. B. Ulrich and Dr. Marc A. Ellsworth are both trainees and contributed equally to the study design, data analyses, and manuscript preparation.

Appendix

Appendix

The manner in which the algorithm used by the Phillips monitoring system mitigates hysteresis has been well described previously [1]. In brief, the monitor generates a QT interval, termed the “raw” QT, that represents an average of measurable QT intervals over a 1-min span. The raw QT is first adjusted for heart rate using an α-trimmed average during the same 60-s interval from which the raw QT was derived. Next, using the Bazett correction formula, a heart-rate-corrected QT interval is generated. The raw QTc is then low-pass filtered, producing a “filtered” QTc. The raw QTc and the filtered QTc are then compared. If the absolute difference between the two falls between the set thresholds, it is considered “qualified.”

In our study, the final QTc documented in the medical record had been computed based on the average of the “qualified” QTc intervals obtained during that same duration. The monitoring system’s validated algorithm helps to establish reliable trends and limits measuring errors due to hysteresis, T-wave abnormalities (low amplitude, biphasic, inverted), a paucity of leads secondary to surface area confinement, baseline wandering from the muscle artifact, and frequent manipulation of the infant or crying. In addition, our use of a 24-h QTc mean for each infant helps to control for the multiple variations in heart rate and QTc values throughout a single day.

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Ulrich, T.J.B., Ellsworth, M.A., Carey, W.A. et al. Heart-Rate-Corrected QT Interval Evolution in Premature Infants During the First Week of Life. Pediatr Cardiol 35, 1363–1369 (2014). https://doi.org/10.1007/s00246-014-0937-z

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  • DOI: https://doi.org/10.1007/s00246-014-0937-z

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