Exercise-induced irregular right heart flow dynamics in adolescents and young adults born preterm

Jacob A Macdonald, Grant S Roberts, Philip A Corrado, Arij G Beshish, Kristin Haraldsdottir, Gregory P Barton, Kara N Goss, Marlowe W Eldridge, Christopher J Francois, Oliver Wieben, Jacob A Macdonald, Grant S Roberts, Philip A Corrado, Arij G Beshish, Kristin Haraldsdottir, Gregory P Barton, Kara N Goss, Marlowe W Eldridge, Christopher J Francois, Oliver Wieben

Abstract

Background: Preterm birth has been linked to an elevated risk of heart failure and cardiopulmonary disease later in life. With improved neonatal care and survival, most infants born preterm are now reaching adulthood. In this study, we used 4D flow cardiovascular magnetic resonance (CMR) coupled with an exercise challenge to assess the impact of preterm birth on right heart flow dynamics in otherwise healthy adolescents and young adults who were born preterm.

Methods: Eleven young adults and 17 adolescents born preterm (< 32 weeks of gestation and < 1500 g birth weight) were compared to 11 young adult and 18 adolescent age-matched controls born at term. Stroke volume, cardiac output, and flow in the main pulmonary artery were quantified with 4D flow CMR. Kinetic energy and vorticity were measured in the right ventricle. All parameters were measured at rest and during exercise at a power corresponding to 70% VO2max for each subject. Multivariate linear regression was used to perform age-adjusted term-preterm comparisons.

Results: With exercise, stroke volume increased 10 ± 21% in term controls and decreased 4 ± 18% in preterm born subjects (p = 0.007). This resulted in significantly reduced capacity to increase cardiac output in response to exercise stress for the preterm group (58 ± 26% increase in controls, 36 ± 27% increase in preterm, p = 0.004). Elevated kinetic energy (KEterm = 71 ± 22 nJ, KEpreterm = 87 ± 38 nJ, p = 0.03) and vorticity (ωterm = 79 ± 16 s-1, ωpreterm = 94 ± 32 s-1, p = 0.01) during diastole in the right ventricle (RV) suggested altered RV flow dynamics in the preterm subjects. Streamline visualizations showed altered structure to the diastolic filling vortices in those born preterm.

Conclusions: For the participants examined here, preterm birth appeared to result in altered right-heart flow dynamics as early as adolescence, especially during diastole. Future studies should evaluate whether the altered dynamics identified here evolves into cardiopulmonary disease later in life. Trial registration None.

Keywords: 4D flow; Cardiovascular magnetic resonance; Exercise; Kinetic energy; Premature; Preterm; Ventricle.

Conflict of interest statement

The University of Wisconsin-Madison receives research support from GE Healthcare. The authors declare that they have no other potential competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Sample setup for exercise imaging. The subject lies in a supine position and steps against the pneumatic pedals of the cardiovascular magnetic resonance (CMR)-compatible exercise stepper (seen at the end of the CMR bed). The pressure supplied to the pedals control resistance. The subject is connected to the stepper with Velcro straps around the feet and a harness around the chest to minimize bulk motion during exercise
Fig. 2
Fig. 2
Changes in heart rate, stroke volume index, and cardiac index with exercised as measured with 4D flow in the main pulmonary artery for term (blue) and preterm (orange) subjects. p-values represent the significance of differences between term and preterm subjects at rest and during exercise
Fig. 3
Fig. 3
Changes in mean peak systolic kinetic energy, mean peak diastolic kinetic energy, systolic energy efficiency, and diastolic energy efficiency with exercise as measured with 4D flow in the right ventricle for term (blue) and preterm (orange) subjects. p-values represent the significance of differences between term and preterm subjects at rest and during exercise. Refer to Fig. 2 for a more detailed legend
Fig. 4
Fig. 4
Changes in peak systolic vorticity and peak diastolic vorticity with exercise for term (blue) and preterm (orange) subjects. p-values represent the significance of differences between term and preterm subjects at rest and during exercise. Refer to Fig. 2 for a more detailed legend
Fig. 5
Fig. 5
Representative right heart streamline visualizations of the entire cardiac cycle in term and preterm subjects during exercise. As indicated in the regions enclosed by the dashed yellow circles, term subjects have clearly structured, circular diastolic filling vortices. Diastolic filling vortices are more chaotic and incoherent in preterm subjects

References

    1. Glass H, Costarino A, Stayer S, Brett C, Cladis F, Davis P. Outcomes for extremely premature infants. Anesth Analg. 2015;120:1337–1351. doi: 10.1213/ANE.0000000000000705.
    1. Raju TNK, Buist AS, Blaisdell CJ, Moxey-Mims M, Saigal S. Adults born preterm: a review of general health and system-specific outcomes. Acta Paediatr Int J Paediatr. 2017;106:1409–1437. doi: 10.1111/apa.13880.
    1. Naumburg E, Axelsson I, Huber D, Söderström L. Some neonatal risk factors for adult pulmonary arterial hypertension remain unknown. Acta Paediatr Int J Paediatr. 2015;104:1104–1108. doi: 10.1111/apa.13205.
    1. Goss KN, Beshish AG, Barton GP, Haraldsdottir K, Levin TS, Tetri LH, et al. Early pulmonary vascular disease in young adults born preterm. Am J Respir Crit Care Med. 2018;198:1549–1558. doi: 10.1164/rccm.201710-2016OC.
    1. Lewandowski AJ, Levy PT, Bates ML, McNamara PJ, Nuyt AM, Goss KN. Impact of the vulnerable preterm heart and circulation on adult cardiovascular disease risk. Hypertension. 2020;76:1028–1037. doi: 10.1161/HYPERTENSIONAHA.120.15574.
    1. Irving RJ, Belton NR, Elton RA, Walker BR. Adult cardiovascular risk factors in premature babies. Lancet. 2000;355:2135–2136. doi: 10.1016/S0140-6736(00)02384-9.
    1. Mulchrone A, Bellofiore A, Douwes JM, Duong N, Beshish AG, Barto GP, et al. Impaired right ventricular-vascular coupling in young adults born preterm. Am J Respir Crit Care Med. 2020;201:615–618. doi: 10.1164/rccm.201904-0767LE.
    1. Barton GP, Torres LA, Goss KN, Eldridge MW, Fain SB. Pulmonary microvascular changes in adult survivors of prematurity: utility of dynamic contrast-enhanced magnetic resonance imaging. Am J Respir Crit Care Med. 2020;202:1471–1473. doi: 10.1164/rccm.202002-0344LE.
    1. Mohamed A, Lamata P, Williamson W, Alsharqi M, Tan CMJ, Burchert H, et al. Multimodality imaging demonstrates reduced right-ventricular function independent of pulmonary physiology in moderately preterm-born adults. JACC Cardiovasc Imaging. 2020;13:2046–2048. doi: 10.1016/j.jcmg.2020.03.016.
    1. Lewandowski AJ, Bradlow WM, Augustine D, Davis EF, Francis J, Singhal A, et al. Right ventricular systolic dysfunction in young adults born preterm. Circulation. 2013;128:713–720. doi: 10.1161/CIRCULATIONAHA.113.002583.
    1. Goss KN, Haraldsdottir K, Beshish AG, Barton GP, Watson AM, Palta M, et al. Association between preterm birth and arrested cardiac growth in adolescents and young adults. JAMA Cardiol. 2020;5:910–919. doi: 10.1001/jamacardio.2020.1511.
    1. Fenster BE, Browning J, Schroeder JD, Schafer M, Podgorski CA, Smyser J, et al. Vorticity is a marker of right ventricular diastolic dysfunction. Am J Physiol Hear Circ Physiol. 2015;309:1087–1093. doi: 10.1152/ajpheart.00278.2015.
    1. Garg P, Crandon S, Swoboda PP, Fent GJ, Foley JRJ, Chew PG, et al. Left ventricular blood flow kinetic energy after myocardial infarction—insights from 4D flow cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2018 doi: 10.1186/s12968-018-0483-6.
    1. Jeong D, Anagnostopoulos PV, Roldan-Alzate A, Srinivasan S, Schiebler ML, Wieben O, et al. Ventricular kinetic energy may provide a novel noninvasive way to assess ventricular performance in patients with repaired tetralogy of Fallot. J Thorac Cardiovasc Surg. 2015;149:1339–1347. doi: 10.1016/j.jtcvs.2014.11.085.
    1. Macdonald JA, Beshish AG, Corrado PA, Barton GP, Goss KN, Eldridge MW, et al. Feasibility of cardiovascular four-dimensional flow MRI during exercise in healthy participants. Radiol Cardiothorac Imaging. 2020 doi: 10.1148/ryct.2020190033.
    1. Haraldsdottir K, Watson AM, Beshish AG, Pegelow DF, Palta M, Tetri LH, et al. Heart rate recovery after maximal exercise is impaired in healthy young adults born preterm. Eur J Appl Physiol. 2019;119:857–866. doi: 10.1007/s00421-019-04075-z.
    1. Haraldsdottir K, Wieben O, Barton G, Goss K, Watson A, Eldridge M. Exercise intolerance in adolescents born preterm associated with left ventricular diastolic dysfunction. FASEB J. 2018;32(Suppl 1):85317.
    1. Hagen EW, Sadek-Badawi M, Albanese A, Palta M. A comparison of Wisconsin Neonatal Intensive Care Units with National data on outcomes and practices. Wis Med J. 2008;107:320–326.
    1. Bull FC, Maslin TS, Armstrong T. Global physical activity questionnaire (GPAQ): nine country reliability and validity study. J Phys Act Heal. 2009;6:790–804. doi: 10.1123/jpah.6.6.790.
    1. Crocker PRE, Bailey DA, Faulkner RA, Kowalski KC, McGrath R. Measuring general levels of physical activity: preliminary evidence for the Physical Activity Questionnaire for Older Children. Med Sci Sport Exerc. 1997;29:1344–1349. doi: 10.1097/00005768-199710000-00011.
    1. Gu T, Korosec FR, Block WF, Fain SB, Turk Q, Lum D, et al. PC VIPR: a high-speed 3D phase-contrast method for flow quantification and high-resolution angiography. Am J Neuroradiol. 2005;26:743–749.
    1. Johnson KM, Lum DP, Turski PA, Block WF, Mistretta CA, Ph D, et al. Improved 3D phase contrast MRI with off-resonance corrected dual echo VIPR. Magn Reson Med. 2008;60:1329–1336. doi: 10.1002/mrm.21763.
    1. Macdonald J, Roberts G, Wieben O. ECG Characterization and correction during exercise stress imaging. Proc 26th Annu ISMRM Meet 2018.
    1. Schrauben EM, Anderson AG, Johnson KM, Wieben O. Respiratory-induced venous blood flow effects using flexible retrospective double-gating. J Magn Reson Imaging. 2015;42:211–216. doi: 10.1002/jmri.24746.
    1. Walker PG, Cranney GB, Scheidegger MB, Waseleski G, Pohost GM, Yoganathan AP. Semiautomated method for noise reduction and background phase error correction in MR phase velocity data. J Magn Reson Imaging. 1993;3:521–530. doi: 10.1002/jmri.1880030315.
    1. Stalder AF, Russe MF, Frydrychowicz A, Bock J, Hennig J, Markl M. Quantitative 2D and 3D phase contrast MRI: optimized analysis of blood flow and vessel wall parameters. Magn Reson Med. 2008;60:1218–1231. doi: 10.1002/mrm.21778.
    1. Pasipoularides A, Shu M, Shah A, Womack MS, Glower DD. Diastolic right ventricular filling vortex in normal and volume overload states. Am J Physiol Hear Circ Physiol. 2003;284:H1064–H1072. doi: 10.1152/ajpheart.00804.2002.
    1. Haraldsdottir K, Watson AM, Pegelow DF, Palta M, Tetri LH, Levin T, et al. Blunted cardiac output response to exercise in adolescents born preterm. Eur J Appl Physiol. 2020 doi: 10.1007/s00421-020-04480-9.
    1. Haraldsdottir K, Watson AM, Goss KN, Beshish AG, Pegelow DF, Palta M, et al. Impaired autonomic function in adolescents born preterm. Physiol Rep. 2018;6:1–9. doi: 10.14814/phy2.13620.
    1. Malhotra R, Bakken K, D’Elia E, Lewis GD. Cardiopulmonary exercise testing in heart failure. JACC Hear Fail. 2016;4:607–616. doi: 10.1016/j.jchf.2016.03.022.
    1. Weisman IM, Marciniuk D, Martinez FJ, Sciurba F, Sue D, Myers J, et al. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003;167:211–277. doi: 10.1164/rccm.167.2.211.
    1. Turley KR. Cardiovascular responses to exercise in children. Sport Med. 1997;24:241–257. doi: 10.2165/00007256-199724040-00003.
    1. Spodick DH, Quarry-Pigott VM. Effects of posture on exercise performance: measurement by systolic time intervals. Circulation. 1973;48:74–78. doi: 10.1161/01.CIR.48.1.74.
    1. Huckstep OJ, Williamson W, Telles F, Burchert H, Bertagnolli M, Herdman C, et al. Physiological stress elicits impaired left ventricular function in preterm-born adults. J Am Coll Cardiol. 2018;71:1347–1356. doi: 10.1016/j.jacc.2018.01.046.
    1. Laskey WK, Ferrari VA, Palevsky HI, Kussmaul WG. Pulmonary artery hemodynamics in primary pulmonary hypertension. J Am Coll Cardiol. 1993;21:406–412. doi: 10.1016/0735-1097(93)90682-Q.
    1. Gupta V, Bustamante M, Fredriksson A, Carlhäll CJ, Ebbers T. Improving left ventricular segmentation in four-dimensional flow MRI using intramodality image registration for cardiac blood flow analysis. Magn Reson Med. 2018;79:554–560. doi: 10.1002/mrm.26674.
    1. Nett EJ, Johnson KM, Frydrychowicz A, Del Rio AM, Schrauben E, Francois CJ, et al. Four-dimensional phase contrast MRI with accelerated dual velocity encoding. J Magn Reson Imaging. 2012;35:1462–1471. doi: 10.1002/jmri.23588.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner