Hostname: page-component-76fb5796d-45l2p Total loading time: 0 Render date: 2024-04-25T14:30:37.468Z Has data issue: false hasContentIssue false

Heart rate variability in the course of chemotherapy and haematopoietic stem cell transplantation for peadiatric patients with haematological malignancies

Published online by Cambridge University Press:  29 May 2020

Honami Kobayashi
Affiliation:
Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Nagano, Japan
Noriko Motoki*
Affiliation:
Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Nagano, Japan
Saori Yokota
Affiliation:
Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Nagano, Japan
Ayako Kanai
Affiliation:
Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Nagano, Japan
Shoko Yamazaki
Affiliation:
Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Nagano, Japan
Masafumi Utsumi
Affiliation:
Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Nagano, Japan
Yozo Nakazawa
Affiliation:
Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Nagano, Japan
*
Author for correspondence: Noriko Motoki, Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto390-8621, Japan. Tel: +81-(0)263-37-2642; Fax: +81-(0)263-37-3089. E-mail: nmotoki@shinshu-u.ac.jp

Abstract

Background:

High-dose chemotherapy and haematopoietic stem cell transplantation are essential for patients with paediatric haematologic diseases, although cardiotoxicity remains a concern. Heart rate variability analysis can evaluate autonomic nervous function interactions with cardiac function.

Objective:

This study aimed to characterise heart rate variability differences between patients undergoing chemotherapy and controls, and the effects of haematopoietic stem cell transplantation on the autonomic nervous system in patients with haematological malignancies.

Methods:

Nineteen patients (11 male, median age: 11.6 years) who received conventional chemotherapy followed by transplantation and 19 non-transplant patients (10 male, median age: 11.5 years) receiving chemotherapy only between 2006 and 2018 for haematological malignancies were retrospectively enrolled. Data from 24-hour Holter monitoring were recorded after chemotherapy and before and after transplantation. Heart rate variability was analysed in patients and 32 matched normal controls.

Results:

There were significant differences between patients and normal controls in all heart rate variability analysis parameters apart from coefficient of variation of RR interval and standard deviation of the average normal RR interval for all 5-minute segments during sleeping. There was a significant difference in the cumulative anthracycline dose and heart rate variability during sleep between the non-transplant and pre-transplant groups. We observed no remarkable differences in time-domain analysis parameters between before and after transplantation, although the low-frequency component of power-spectrum analysis during awake hours was significantly decreased after transplantation.

Conclusion:

Conventional chemotherapy for paediatric haematologic diseases may be a risk factor for autonomic dysfunction. Further declines in heart rate variability after transplantation appear minor.

Type
Original Article
Copyright
© The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

Honami Kobayashi and Noriko Motoki contributed equally to this work.

References

Pui, CH, Campana, D, Evans, WE.Childhood acute lymphoblastic leukemia: current status and future perspectives. Lancet Oncol 2001; 2: 597607.10.1016/S1470-2045(01)00516-2CrossRefGoogle ScholarPubMed
Pui, CH, Evans, WE.Acute lymphoblastic leukemia. N Engl J Med 1998; 339: 605615.10.1056/NEJM199808273390907CrossRefGoogle ScholarPubMed
Tomizawa, D, Tabuchi, K, Kinoshita, A, et al.Repetitive cycles of high-dose cytarabine are effective for childhood acute myeloid leukemia: long-term outcome of the children with AML treated on two consecutive trials of Tokyo children’s cancer study group. Pediatr Blood Cancer 2007; 49: 127132.10.1002/pbc.20944CrossRefGoogle ScholarPubMed
Kleiger, RE, Miller, JP, Bigger, JT Jr, Moss, AJ.Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 1987; 59: 256262.10.1016/0002-9149(87)90795-8CrossRefGoogle ScholarPubMed
Bigger, JTJr, Fleiss, JL, Steinman, RC, Rolnitzky, LM, Kleiger, RE, Rottman, JN.Frequency domain measures of heart period variability and mortality after myocardial infarction. Circulation 1992; 85: 164171.10.1161/01.CIR.85.1.164CrossRefGoogle ScholarPubMed
La Rovere, MT, Bigger, JT Jr, Marcus, FI, Mortara, A, Schwartz, PJ.Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (autonomic tone and reflexes after myocardial infarction) investigators. Lancet 1998; 351: 478484.10.1016/S0140-6736(97)11144-8CrossRefGoogle ScholarPubMed
Frenneaux, MP.Autonomic changes in patients with heart failure and in post-myocardial infarction patients. Heart 2004; 90: 12481255.10.1136/hrt.2003.026146CrossRefGoogle ScholarPubMed
Guzzetti, S, Cogliati, C, Turiel, M, Crema, C, Lombardi, F, Malliani, A.Sympathetic predominance followed by functional denervation in the progression of chronic heart failure. Eur Heart J 1995; 16: 11001107.10.1093/oxfordjournals.eurheartj.a061053CrossRefGoogle ScholarPubMed
Ajiki, K, Murakawa, Y, Yanagisawa-Miwa, A, et al.Autonomic nervous system activity in idiopathic dilated cardiomyopathy and in hypertrophic cardiomyopathy. Am J Cardiol 1993; 71: 13161320.10.1016/0002-9149(93)90547-PCrossRefGoogle ScholarPubMed
Poręba, M, Poręba, R, Gać, P, et al.Heart rate variability and heart rate turbulence in patients with hematologic malignancies subjected to high-dose chemotherapy in the course of hematopoietic stem cell transplantation. Ann Noninvasive Electrocardiol 2014; 19: 157165.10.1111/anec.12108CrossRefGoogle ScholarPubMed
Nakane, T, Nakamae, M, Koh, H, et al.Autonomic nervous system pretransplant malfunction is a powerful predictor of survival after allogeneic hematopoietic. Cell Transplant 2017; 101: 28012809.10.1097/TP.0000000000001813CrossRefGoogle ScholarPubMed
Ewer, MS, Benjamin, RS, Yeh, ETH.Cardiac complications of cancer treatment. In: Kufe, DW, Pollock, RE, Weichselbaum, RR, et al. (eds). Holland-Frei Cancer Medicine, 6th edn. BC Decker, Hamilton, 2003.Google Scholar
Sakata-Yanagimoto, M, Kanda, Y, Nakagawa, M, et al.Predictors for severe cardiac complications after hematopoietic stem cell transplantation. Bone Marrow Transplant 2004; 33: 10431047.10.1038/sj.bmt.1704487CrossRefGoogle ScholarPubMed
Luutonen, S, Antila, K, Neuvonen, P, Räihä, I, Rajala, T, Sourander, L.Spectral analysis of heart rate variability in evaluation of sympathetic function in elderly subjects. Age Ageing 1994; 23: 473477.10.1093/ageing/23.6.473CrossRefGoogle ScholarPubMed
Taylor, JA, Carr, DL, Myers, CW, Eckberg, DL.Mechanisms underlying very-low-frequency RR-interval oscillations in humans. Circulation 1998; 98: 547555.10.1161/01.CIR.98.6.547CrossRefGoogle ScholarPubMed
Nazir, HF, AlFutaisi, A, Zacharia, M, et al.Vincristine-induced neuropathy in pediatric patients with acute lymphoblastic leukemia in Oman: frequent autonomic and more severe cranial nerve involvement. Pediatr Blood Cancer 2017; 64: e26677.10.1002/pbc.26677CrossRefGoogle ScholarPubMed
Hirvonen, HE, Salmi, TT, Heinonen, E, Antila, KJ, Välimäki, IA.Vincristine treatment of acute lymphoblastic leukemia induces transient autonomic cardioneuropathy. Cancer 1989; 64: 801805.10.1002/1097-0142(19890815)64:4<801::AID-CNCR2820640406>3.0.CO;2-E3.0.CO;2-E>CrossRefGoogle ScholarPubMed
Caru, M, Corbin, D, Périé, D, et al.Doxorubicin treatments induce signify changes on the cardiac autonomic nerve system in childhood acute lymphoblastic leukemia long-term survivors. Clin Res Cardiol 2019; 108: 10001008.10.1007/s00392-019-01427-9CrossRefGoogle Scholar
Straburzynska-Migaj, E, Ochotny, R, Wachowiak-Baszynska, A, et al.Cytokines and heart rate variability in patients with chronic heart failure. Kardiol Pol 2005; 63: 478487.Google ScholarPubMed
Kunz-Ebrecht, SR, Mohamed-Ali, V, Feldman, PJ, Kirschbaum, C, Steptoe, A.Cortisol responses to mild psychological stress are inversely associated with proinflammatory cytokines. Brain Behav Immun 2003; 17: 373383.10.1016/S0889-1591(03)00029-1CrossRefGoogle ScholarPubMed
Bellenger, CR, Fuller, JT, Thomson, RL, Davison, K, Robertson, EY, Buckley, JD.Monitoring athletic training status through autonomic heart rate regulation: a systemic review and meta-analysis. Sports Med 2016; 46: 14611486.10.1007/s40279-016-0484-2CrossRefGoogle Scholar
Acharya, UR, Kannathal, N, Krishnan, SM.Comprehensive analysis of cardiac health using heart rate signals. Physiol Meas J 2004; 25: 11301151.Google Scholar
Acharya, UR, Kannathal, N, Seng, OW, Ping, LY, Chua, T.Heart rate analysis in normal subjects of various age groups. Biomed Eng Online 2004; 3: 24.10.1186/1475-925X-3-24CrossRefGoogle Scholar
Schwartz, JB, Gibb, WJ, Tran, T.Aging effects on heart rate variation. J Gerontol 1991; 46: M99M106.10.1093/geronj/46.3.M99CrossRefGoogle ScholarPubMed
Finley, JP, Nungent, ST, Hellenbrand, W.Heart rate variability in children, spectral analysis of developmental changes between 5 and 25 years. Can J Physiol Pharmacol 1987; 65: 20482052.10.1139/y87-320CrossRefGoogle Scholar
Lipsitz, LA, Mietus, J, Moody, GB, Goldberger, AL.Spectral characteristics of heart rate variability before and during postural tilt: relations to aging and risk of syncope. Circulation 1990; 81: 18031810.10.1161/01.CIR.81.6.1803CrossRefGoogle ScholarPubMed
Borchert-Mörlins, B, Memaran, N, Sauer, M, et al.Cardiovascular risk factors and subclinical organ damage after hematopoietic stem cell transplantation in pediatric age. Bone Marrow Transplant 2018; 53: 983992.10.1038/s41409-018-0104-xCrossRefGoogle ScholarPubMed
Baker, KS, Chow, E, Steinberger, J.Metabolic syndrome and cardiovascular risk in survivors after hematopoietic cell transplantation. Bone Marrow Transplant 2012; 47: 619625.10.1038/bmt.2011.118CrossRefGoogle ScholarPubMed
Antman, EM, Anbe, DT, Armstrong, PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 2004; 110: e82.e292.Google Scholar