Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Diastolic function in newborn infants: understanding pathophysiology, diagnosis and clinical relevance

Pediatric Research (2025)Cite this article

Abstract

Diastolic function, the combined effect of myocardial relaxation, recoil forces, stiffness and atrial function, describes the ability of the ventricle to fill up with blood and prepare a stroke volume for ejection. Diastolic dysfunction (DD), also described as ‘an increased resistance to filling’ for example due to impaired relaxation, chamber stiffness, volume load or pericardial restraint, is a situation whereby normal filling is only achieved with elevated filling pressure and higher atrial pressure. Diastolic dysfunction can progress to diastolic heart failure, a clinical syndrome with respiratory deterioration and/or edema and is associated with morbidity and mortality. Diastolic dysfunction can be diagnosed with a multi-modal multi-parameter echocardiography approach, but further development of newborn specific diagnostic algorithms is required. Diastolic dysfunction often precedes systolic dysfunction and thus provides an opportunity for management directives in newborns at high risk of heart failure: with a patent ductus arteriosus, septic shock, pulmonary hypertension, congenital diaphragmatic hernia, small for gestational age infants and infants with bronchopulmonary dysplasia. This review describes the current understanding of the physiology and pathophysiology of diastolic function in newborn infants.

Impact

  • Diastolic dysfunction is common in the neonatal intensive care and can lead to diastolic heart failure.

  • Understanding pathophysiology and clinical relevance allows for targeted treatments and supportive care.

  • Improved cardiovascular care during a crucial part of development can improve short- and long-term outcomes and limit early heart failure.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Schematic representation of a typical left ventricular (LV, red line) and left atrial (LA, blue line) pressures during diastole in a preterm infant.
Fig. 2: Schematic left ventricular pressure-volume loops illustrating mechanistic pathways leading to increased LV end diastolic pressure.
Fig. 3: Schematic overview of risk factors for LV diastolic dysfunction and mechanistic pathways towards diastolic heart failure.

Similar content being viewed by others

References

  1. Nagueh, S. F. Left Ventricular Diastolic Function. Underst. Pathophysiol., Diagnosis, Prognosis Echocardiogr. JACC Cardiovasc Imaging 13, 228–244, https://doi.org/10.1016/j.jcmg.2018.10.038 (2020).

    Article  Google Scholar 

  2. Mekkaoui, C. et al. Diffusion MRI tractography of the developing human fetal heart. PLoS One 8, e72795, https://doi.org/10.1371/journal.pone.0072795 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Bensley, J. G., Moore, L., De Matteo, R., Harding, R. & Black, M. J. Impact of preterm birth on the developing myocardium of the neonate. Pediatr. Res 83, 880–888, https://doi.org/10.1038/pr.2017.324 (2018).

    Article  PubMed  Google Scholar 

  4. Lahmers, S., Wu, Y., Call, D. R., Labeit, S. & Granzier, H. Developmental control of titin isoform expression and passive stiffness in fetal and neonatal myocardium. Circ. Res 94, 505–513, https://doi.org/10.1161/01.res.0000115522.52554.86 (2004).

    Article  PubMed  CAS  Google Scholar 

  5. Sørensen K. et al. Changes in left ventricular diastolic flow dynamics in the neonatal transition period and beyond. Am. J. Physiol. Heart Circ. Physiol. 8, https://doi.org/10.1152/ajpheart.00214.2025 (2025).

  6. Pfeffer, M. A., Shah, A. M. & Borlaug, B. A. Heart Failure With Preserved Ejection Fraction In Perspective. Circ. Res 124, 1598–1617, https://doi.org/10.1161/circresaha.119.313572 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. de Waal, K., Phad, N. & Crendal, E. Echocardiography algorithms to assess high left atrial pressure and grade diastolic function in preterm infants. Echocardiography 40, 1099–1106, https://doi.org/10.1111/echo.15686 (2023).

    Article  PubMed  Google Scholar 

  8. de Waal, K., Costley, N., Phad, N. & Crendal, E. Left Ventricular Diastolic Dysfunction and Diastolic Heart Failure in Preterm Infants. Pediatr. Cardiol. 40, 1709–1715, https://doi.org/10.1007/s00246-019-02208-x (2019).

    Article  PubMed  Google Scholar 

  9. Kharrat, A., Nissimov, S., Zhu, F., Deshpande, P. & Jain, A. Cardiopulmonary Physiology of Hypoxemic Respiratory Failure Among Preterm Infants with Septic Shock. J. Pediatr. 278, 114384. https://doi.org/10.1016/j.jpeds.2024.114384 (2024).

    Article  PubMed  CAS  Google Scholar 

  10. Nayak, V. et al. Subclinical myocardial dysfunction among fetal growth restriction neonates: a case-control study. J. Matern Fetal Neonatal Med 37, 2392783. https://doi.org/10.1080/14767058.2024.2392783 (2024).

    Article  PubMed  Google Scholar 

  11. Fouzas, S. et al. Neonatal cardiac dysfunction in intrauterine growth restriction. Pediatr. Res 75, 651–657, https://doi.org/10.1038/pr.2014.22 (2014).

    Article  PubMed  Google Scholar 

  12. Rigotti, C., Doni, D., Zannin, E., Abdelfattah, A. S. & Ventura, M. L. Left ventricular diastolic function and respiratory outcomes in preterm infants: a retrospective study. Pediatr. Res 93, 1010–1016, https://doi.org/10.1038/s41390-022-02216-3 (2023).

    Article  PubMed  CAS  Google Scholar 

  13. Muhsen, W., Nestaas, E., Hosking, J. & Latour, J. M. Echocardiography parameters used in identifying right ventricle dysfunction in preterm infants with early bronchopulmonary dysplasia: A scoping review. Front Pediatr. 11, 1114587. https://doi.org/10.3389/fped.2023.1114587 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Altit, G. et al. Altered biventricular function in neonatal hypoxic-ischaemic encephalopathy: a case-control echocardiographic study. Cardiol. Young-. 33, 1587–1596, https://doi.org/10.1017/s1047951122002839 (2023).

    Article  PubMed  Google Scholar 

  15. Patel, N., Massolo, A. C. & Kipfmueller, F. Congenital diaphragmatic hernia-associated cardiac dysfunction. Semin Perinatol. 44, 151168. https://doi.org/10.1053/j.semperi.2019.07.007 (2020).

    Article  PubMed  Google Scholar 

  16. Burkett D. A. et al. Impact of Pulmonary Hemodynamics and Ventricular Interdependence on Left Ventricular Diastolic Function in Children With Pulmonary Hypertension. Circ Cardiovasc. Imaging. 9, https://doi.org/10.1161/circimaging.116.004612 (2016).

  17. Friedberg, M. K. et al. Left ventricular diastolic mechanical dyssynchrony and associated clinical outcomes in children with dilated cardiomyopathy. Circ. Cardiovasc Imaging 1, 50–57, https://doi.org/10.1161/circimaging.108.782086 (2008).

    Article  PubMed  Google Scholar 

  18. Heidenreich, P. A. et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 145, e895–e1032, https://doi.org/10.1161/cir.0000000000001063 (2022).

    Article  PubMed  Google Scholar 

  19. Hsu, D. T. & Pearson, G. D. Heart failure in children: part I: history, etiology, and pathophysiology. Circ. Heart Fail 2, 63–70, https://doi.org/10.1161/circheartfailure.108.820217 (2009).

    Article  PubMed  Google Scholar 

  20. Ross, R. D. The Ross classification for heart failure in children after 25 years: a review and an age-stratified revision. Pediatr. Cardiol. 33, 1295–1300, https://doi.org/10.1007/s00246-012-0306-8 (2012).

    Article  PubMed  Google Scholar 

  21. de Waal, K. et al. The association between patterns of early respiratory disease and diastolic dysfunction in preterm infants. J. Perinatol.: Off. J. Calif. Perinat. Assoc. 43, 1268–1273, https://doi.org/10.1038/s41372-023-01608-5 (2023).

    Article  CAS  Google Scholar 

  22. Nguyen, M. B. et al. Understanding Complex Interactions in Pediatric Diastolic Function Assessment. J. Am. Soc. Echocardiogr. 35, 868–877.e5, https://doi.org/10.1016/j.echo.2022.03.017 (2022).

    Article  PubMed  Google Scholar 

  23. Kellenberger, C. J., Lovrenski, J., Semple, T. & Caro-Domínguez, P. Neonatal cardiorespiratory imaging-a multimodality state-of-the-art review. Pediatr. Radio. 53, 660–676 https://doi.org/10.1007/s00247-022-05504-6 (2023).

    Article  Google Scholar 

  24. Schmitz, L., Koch, H., Bein, G. & Brockmeier, K. Left ventricular diastolic function in infants, children, and adolescents. Reference values and analysis of morphologic and physiologic determinants of echocardiographic Doppler flow signals during growth and maturation. J. Am. Coll. Cardiol. 32, 1441–1448, https://doi.org/10.1016/s0735-1097(98)00379-9 (1998).

    Article  PubMed  CAS  Google Scholar 

  25. Schmitz, L., Stiller, B., Koch, H., Koehne, P. & Lange, P. Diastolic left ventricular function in preterm infants with a patent ductus arteriosus: a serial Doppler echocardiography study. Early Hum. Dev. 76, 91–100 (2004).

    Article  PubMed  Google Scholar 

  26. Schmitz, L., Xanthopoulos, A., Koch, H. & Lange, P. E. Doppler flow parameters of left ventricular filling in infants: how long does it take for the maturation of the diastolic function in a normal left ventricle to occur? Pediatr. Cardiol. 25, 482–491, https://doi.org/10.1007/s00246-003-0605-1 (2004).

    Article  PubMed  CAS  Google Scholar 

  27. Schmitz, L., Xanthopoulos, A. & Lange, P. E. Isovolumic relaxation time shortens significantly during the three months after birth. J. Am. Soc. Echocardiogr. 17, 275–276, https://doi.org/10.1016/j.echo.2003.10.027 (2004).

    Article  PubMed  Google Scholar 

  28. Bussmann, N. et al. Early diastolic dysfunction and respiratory morbidity in premature infants: an observational study. J. Perinatol.: Off. J. Calif. Perinat. Assoc. 38, 1205–1211, https://doi.org/10.1038/s41372-018-0147-2 (2018).

    Article  Google Scholar 

  29. Ciccone, M. M. et al. Different functional cardiac characteristics observed in term/preterm neonates by echocardiography and tissue doppler imaging. Early Hum. Dev. 87, 555–558, https://doi.org/10.1016/j.earlhumdev.2011.04.012 (2011).

    Article  PubMed  Google Scholar 

  30. Bokiniec, R., Własienko, P., Szymkiewicz-Dangel, J. & Borszewska-Kornacka, M. K. Doppler tissue imaging assessment of myocardial velocities and atrioventricular time intervals in term newborn infants during the neonatal period. Kardiol. Pol. 71, 1154–1160, https://doi.org/10.5603/kp.2013.0296 (2013).

    Article  PubMed  Google Scholar 

  31. Petoello, E., Kerkow, E., Phad, N., Ficial, B. & de Waal, K. Which left atrial volume measurement should we use in the neonatal intensive care? Early Hum. Dev. 191, 105985. https://doi.org/10.1016/j.earlhumdev.2024.105985 (2024).

    Article  PubMed  Google Scholar 

  32. Agata, Y. et al. Changes in pulmonary venous flow pattern during early neonatal life. Br. Heart J. 71, 182–186, https://doi.org/10.1136/hrt.71.2.182 (1994).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Hong, Y. M. & Choi, J. Y. Pulmonary venous flow from fetal to neonatal period. Early Hum. Dev. 57, 95–103, https://doi.org/10.1016/s0378-3782(99)00058-4 (2000).

    Article  PubMed  CAS  Google Scholar 

  34. Erickson, C. T. et al. Progression of left ventricular diastolic function in the neonate and early childhood from transmitral color M-mode filling analysis. Pediatr. Res 89, 987–995, https://doi.org/10.1038/s41390-020-1011-6 (2021).

    Article  PubMed  CAS  Google Scholar 

  35. de Waal, K., Petoello, E., Crendal, E. & Phad, N. Reference ranges of left ventricular diastolic multimodal ultrasound parameters in stable preterm infants in the early and late neonatal intensive care admission period. J. Perinatol. https://doi.org/10.1038/s41372-025-02278-1 (2025).

    Article  PubMed  PubMed Central  Google Scholar 

  36. James, A., Corcoran, J. D., Mertens, L., Franklin, O. & El-Khuffash, A. Left Ventricular Rotational Mechanics in Preterm Infants Less Than 29 Weeks’ Gestation over the First Week after Birth. J. Am. Soc. Echocardiogr. 28, 808–17.e1, https://doi.org/10.1016/j.echo.2015.02.015 (2015).

    Article  PubMed  Google Scholar 

  37. Smith, A. et al. Comparison of left ventricular rotational mechanics between term and extremely premature infants over the first week of age. Open Heart. 8, https://doi.org/10.1136/openhrt-2020-001458 (2021).

  38. Mourani, P. M. et al. Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia. Am. J. Respir. Crit. Care Med 191, 87–95, https://doi.org/10.1164/rccm.201409-1594OC (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Das, B. et al. Heart Failure with Preserved Ejection Fraction in Children. Pediatr. Cardiol. 44, 513–529, https://doi.org/10.1007/s00246-022-02960-7 (2023).

    Article  PubMed  Google Scholar 

  40. Bohn, M. K. et al. Cardiac Biomarkers in Pediatrics: An Undervalued Resource. Clin. Chem. 67, 947–958, https://doi.org/10.1093/clinchem/hvab063 (2021).

    Article  PubMed  Google Scholar 

  41. Nagueh, S. F. et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur. J. Echocardiogr. 10, 165–193, https://doi.org/10.1093/ejechocard/jep007 (2009).

    Article  PubMed  Google Scholar 

  42. Nagueh, S. F. et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J. Am. Soc. Echocardiogr. 29, 277–314, https://doi.org/10.1016/j.echo.2016.01.011 (2016).

    Article  PubMed  Google Scholar 

  43. Ficial, B. et al. Feasibility, Reproducibility and Reference Ranges of Left Atrial Strain in Preterm and Term Neonates in the First 48 h of Life. Diagnostics (Basel). 12, https://doi.org/10.3390/diagnostics12020350 (2022).

  44. Jain, A. et al. Left Ventricular Function in Healthy Term Neonates During the Transitional Period. J Pediatr. 28,https://doi.org/10.1016/j.jpeds.2016.11.003 (2016).

  45. Kozak-Barany, A., Jokinen, E., Saraste, M., Tuominen, J. & Valimaki, I. Development of left ventricular systolic and diastolic function in preterm infants during the first month of life: a prospective follow-up study. J. Pediatr. 139, 539–545, https://doi.org/10.1067/mpd.2001.118199 (2001).

    Article  PubMed  CAS  Google Scholar 

  46. de Waal, K., Phad, N. & Boyle, A. Left atrium function and deformation in very preterm infants with and without volume load. Echocardiography 35, 1818–1826, https://doi.org/10.1111/echo.14140 (2018).

    Article  PubMed  Google Scholar 

  47. Di Maria, M. V. et al. Maturational Changes in Diastolic Longitudinal Myocardial Velocity in Preterm Infants. J. Am. Soc. Echocardiogr. 28, 1045–1052, https://doi.org/10.1016/j.echo.2015.04.016 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Hirose, A. et al. Evolution of left ventricular function in the preterm infant. J. Am. Soc. Echocardiogr. 28, 302–308, https://doi.org/10.1016/j.echo.2014.10.017 (2015).

    Article  PubMed  Google Scholar 

  49. de Waal, K. et al. The association between patterns of early respiratory disease and diastolic dysfunction in preterm infants. J. Perinatol. 23, https://doi.org/10.1038/s41372-023-01608-5 (2023).

  50. Harada, K., Takahashi, Y., Tamura, M., Orino, T. & Takada, G. Serial echocardiographic and Doppler evaluation of left ventricular systolic performance and diastolic filling in premature infants. Early Hum. Dev. 54, 169–180, https://doi.org/10.1016/s0378-3782(98)00093-0 (1999).

    Article  PubMed  CAS  Google Scholar 

  51. Sirc, J., Dempsey, E. M. & Miletin, J. Diastolic ventricular function improves during the first 48-hours-of-life in infants weighting <1250 g. Acta Paediatr. 104, e1–e6, https://doi.org/10.1111/apa.12788 (2015).

    Article  PubMed  CAS  Google Scholar 

  52. Ficial, B. et al. Left atrial strain assessment unveils left ventricular diastolic dysfunction in neonates with transient tachypnea of the newborn: A prospective observational study. Pediatr. Pulmonol. 59, 2910–2921, https://doi.org/10.1002/ppul.27156 (2024).

    Article  PubMed  Google Scholar 

  53. Matsuda, M., Anderson-Morris, J. & Raj, J. U. Microvascular pressures in isolated perfused immature lamb lungs: effects of flow rate, left atrial pressure and surfactant therapy. Biol. Neonate 70, 349–358, https://doi.org/10.1159/000244386 (1996).

    Article  PubMed  CAS  Google Scholar 

  54. Scholl, J. E. & Yanowitz, T. D. Pulmonary hemorrhage in very low birth weight infants: a case-control analysis. J. Pediatr. 166, 1083–1084, https://doi.org/10.1016/j.jpeds.2014.12.032 (2015).

    Article  PubMed  Google Scholar 

  55. Kappico, J. M. et al. Pulmonary hemorrhage in extremely low birth weight infants: Significance of the size of left to right shunting through a valve incompetent patent foramen ovale. J. Perinatol. 42, 1233–1237, https://doi.org/10.1038/s41372-022-01464-9 (2022).

    Article  PubMed  Google Scholar 

  56. Eriksen, B. H. et al. Myocardial function in premature infants: a longitudinal observational study. BMJ Open. 3, https://doi.org/10.1136/bmjopen-2012-002441 (2013).

  57. Helfer, S., Schmitz, L., Buhrer, C. & Czernik, C. Tissue Doppler-derived strain and strain rate during the first 28 days of life in very low birth weight infants. Echocardiography 31, 765–772, https://doi.org/10.1111/echo.12463 (2014).

    Article  PubMed  Google Scholar 

  58. James, A. T. et al. Assessment of myocardial performance in preterm infants less than 29 weeks gestation during the transitional period. Early Hum. Dev. 90, 829–835, https://doi.org/10.1016/j.earlhumdev.2014.09.004 (2014).

    Article  PubMed  Google Scholar 

  59. Lee, A. et al. Tissue Doppler imaging in very preterm infants during the first 24 h of life: an observational study. Arch. Dis. Child Fetal Neonatal Ed. 99, F64–F69, https://doi.org/10.1136/archdischild-2013-304197 (2014).

    Article  PubMed  CAS  Google Scholar 

  60. Saleemi, M. S., El-Khuffash, A., Franklin, O. & Corcoran, J. D. Serial changes in myocardial function in preterm infants over a four week period: the effect of gestational age at birth. Early Hum. Dev. 90, 349–352, https://doi.org/10.1016/j.earlhumdev.2014.04.012 (2014).

    Article  PubMed  Google Scholar 

  61. de Waal, K., Phad, N., Collins, N. & Boyle, A. Cardiac remodeling in preterm infants with prolonged exposure to a patent ductus arteriosus. Congenit. Heart Dis. 12, 364–372, https://doi.org/10.1111/chd.12454 (2017).

    Article  PubMed  Google Scholar 

  62. Friedberg, M. K., Silverman, N. H., Dubin, A. M. & Rosenthal, D. N. Mechanical dyssynchrony in children with systolic dysfunction secondary to cardiomyopathy: a Doppler tissue and vector velocity imaging study. J. Am. Soc. Echocardiogr. 20, 756–763, https://doi.org/10.1016/j.echo.2006.11.007 (2007).

    Article  PubMed  Google Scholar 

  63. de Waal, K., Crendal, E. & Boyle, A. Left ventricular vortex formation in preterm infants assessed by blood speckle imaging. Echocardiography 36, 1364–1371, https://doi.org/10.1111/echo.14391 (2019).

    Article  PubMed  Google Scholar 

  64. Dikshit, K. et al. Renal and extrarenal hemodynamic effects of furosemide in congestive heart failure after acute myocardial infarction. N. Engl. J. Med 288, 1087–1090, https://doi.org/10.1056/nejm197305242882102 (1973).

    Article  PubMed  CAS  Google Scholar 

  65. Romero-Lopez, M. et al. The effect of furosemide on extremely premature infants treated with nonsteroidal anti-inflammatory drugs for persistent patent ductus arteriosus. J. Perinatol. 45, 399–401, https://doi.org/10.1038/s41372-024-02148-2 (2025).

    Article  PubMed  Google Scholar 

  66. Huang, X., Dorhout Mees, E., Vos, P., Hamza, S. & Braam, B. Everything we always wanted to know about furosemide but were afraid to ask. Am. J. Physiol. Ren. Physiol. 310, F958–F971, https://doi.org/10.1152/ajprenal.00476.2015 (2016).

    Article  CAS  Google Scholar 

  67. El-Khuffash, A. F., Jain, A. & McNamara, P. J. Ligation of the patent ductus arteriosus in preterm infants: understanding the physiology. J. Pediatr. 162, 1100–1106, https://doi.org/10.1016/j.jpeds.2012.12.094 (2013).

    Article  PubMed  Google Scholar 

  68. Bischoff, A. R. et al. Left ventricular function before and after percutaneous patent ductus arteriosus closure in preterm infants. Pediatr. Res 94, 213–221, https://doi.org/10.1038/s41390-022-02372-6 (2023).

    Article  PubMed  Google Scholar 

  69. Bischoff, A. R. et al. Cardiorespiratory Instability after Percutaneous Patent Ductus Arteriosus Closure: A Multicenter Cohort Study. J. Pediatr. 271, 114052. https://doi.org/10.1016/j.jpeds.2024.114052 (2024).

    Article  PubMed  Google Scholar 

  70. Villamor, E. et al. Patent Ductus Arteriosus and Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension: A Bayesian Meta-Analysis. JAMA Netw. Open 6, e2345299, https://doi.org/10.1001/jamanetworkopen.2023.45299 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Islam, J. Y., Keller, R. L., Aschner, J. L., Hartert, T. V. & Moore, P. E. Understanding the Short- and Long-Term Respiratory Outcomes of Prematurity and Bronchopulmonary Dysplasia. Am. J. Respir. Crit. Care Med 192, 134–156, https://doi.org/10.1164/rccm.201412-2142PP (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Varghese, N. P., Altit, G., Gubichuk, M. M. & Siddaiah, R. Navigating Diagnostic and Treatment Challenges of Pulmonary Hypertension in Infants with Bronchopulmonary Dysplasia. J. Clin. Med. 13, https://doi.org/10.3390/jcm13123417 (2024).

  73. Sehgal, A., South, A. M. & Menahem, S. Systemic hemodynamics and pediatric lung disease: mechanistic links and therapeutic relevance. Am. J. Physiol. Heart Circ. Physiol. 327, H454–H459, https://doi.org/10.1152/ajpheart.00271.2024 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Gopagondanahalli, K. R. et al. Characterizing the Role of Left Ventricular Indices and Biventricular Interaction in Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension in Extreme Prematurity. Neonatology 122, 210–221, https://doi.org/10.1159/000542980 (2025).

    Article  PubMed  CAS  Google Scholar 

  75. Sullivan, R. T. et al. Role of left atrial hypertension in pulmonary hypertension associated with bronchopulmonary dysplasia. Front Pediatr. 10, 1012136. https://doi.org/10.3389/fped.2022.1012136 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Bokiniec, R., Wlasienko, P., Borszewska-Kornacka, M. & Szymkiewicz-Dangel, J. Evaluation of left ventricular function in preterm infants with bronchopulmonary dysplasia using various echocardiographic techniques. Echocardiography 34, 567–576, https://doi.org/10.1111/echo.13488 (2017).

    Article  PubMed  Google Scholar 

  77. Greer, J. Pathophysiology of cardiovascular dysfunction in sepsis. BJA Educ. 15, 316–321, https://doi.org/10.1093/bjaceaccp/mkv003 (2015).

    Article  Google Scholar 

  78. Sanfilippo, F. et al. Diastolic dysfunction and mortality in septic patients: a systematic review and meta-analysis. Intensive Care Med 41, 1004–1013, https://doi.org/10.1007/s00134-015-3748-7 (2015).

    Article  PubMed  Google Scholar 

  79. Sanfilippo, F. et al. Echocardiographic Parameters and Mortality in Pediatric Sepsis: A Systematic Review and Meta-Analysis. Pediatr. Crit. Care Med 22, 251–261, https://doi.org/10.1097/pcc.0000000000002622 (2021).

    Article  PubMed  Google Scholar 

  80. Kharrat, A. & Jain, A. Hemodynamic dysfunction in neonatal sepsis. Pediatr. Res 91, 413–424, https://doi.org/10.1038/s41390-021-01855-2 (2022).

    Article  PubMed  Google Scholar 

  81. Gorantiwar, S. & de Waal, K. Progression from sepsis to septic shock and time to treatments in preterm infants with late-onset sepsis. J. Paediatr. Child Health 57, 1905–1911, https://doi.org/10.1111/jpc.15606 (2021).

    Article  PubMed  Google Scholar 

  82. Johnston, N. & de Waal, K. Clinical and haemodynamic characteristics of preterm infants with early onset sepsis. J. Paediatr. Child Health 58, 2267–2272, https://doi.org/10.1111/jpc.16218 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  83. de Waal, K. & Petoello, E. Assessing fluid responsiveness with ultrasound in the neonatal intensive care setting: the mini-fluid challenge. Eur. J. Pediatr. 183, 1947–1951, https://doi.org/10.1007/s00431-024-05425-6 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Bidegain, M. et al. Vasopressin for refractory hypotension in extremely low birth weight infants. J. Pediatr. 157, 502–504, https://doi.org/10.1016/j.jpeds.2010.04.038 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Nestaas, E. & Walsh, B. H. Hypothermia and Cardiovascular Instability. Clin. Perinatol. 47, 575–592, https://doi.org/10.1016/j.clp.2020.05.012 (2020).

    Article  PubMed  Google Scholar 

  86. Giesinger, R. E., Bailey, L. J., Deshpande, P. & McNamara, P. J. Hypoxic-Ischemic Encephalopathy and Therapeutic Hypothermia: The Hemodynamic Perspective. J. Pediatr. 180, 22–30.e2, https://doi.org/10.1016/j.jpeds.2016.09.009 (2017).

    Article  PubMed  Google Scholar 

  87. Sehgal, A., Linduska, N. & Huynh, C. Cardiac adaptation in asphyxiated infants treated with therapeutic hypothermia. J. Neonatal Perinat. Med 12, 117–125, https://doi.org/10.3233/npm-1853 (2019).

    Article  CAS  Google Scholar 

  88. Post, H. et al. Cardiac function during mild hypothermia in pigs: increased inotropy at the expense of diastolic dysfunction. Acta Physiol. (Oxf.) 199, 43–52, https://doi.org/10.1111/j.1748-1716.2010.02083.x (2010).

    Article  PubMed  CAS  Google Scholar 

  89. Rodriguez, M. J., Martinez-Orgado, J., Corredera, A., Serrano, I. & Arruza, L. Diastolic Dysfunction in Neonates With Hypoxic-Ischemic Encephalopathy During Therapeutic Hypothermia: A Tissue Doppler Study. Front Pediatr. 10, 880786. https://doi.org/10.3389/fped.2022.880786 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Kumagai, T. et al. Correlation between echocardiographic superior vena cava flow and short-term outcome in infants with asphyxia. Early Hum. Dev. 89, 307–310, https://doi.org/10.1016/j.earlhumdev.2012.10.011 (2013).

    Article  PubMed  Google Scholar 

  91. Gebauer, C. M., Knuepfer, M., Robel-Tillig, E., Pulzer, F. & Vogtmann, C. Hemodynamics among neonates with hypoxic-ischemic encephalopathy during whole-body hypothermia and passive rewarming. Pediatrics 117, 843–850, https://doi.org/10.1542/peds.2004-1587 (2006).

    Article  PubMed  Google Scholar 

  92. Konstam, M. A. et al. Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association. Circulation 137, e578–e622, https://doi.org/10.1161/CIR.0000000000000560 (2018).

    Article  PubMed  Google Scholar 

  93. Hsia, H. H. & Haddad, F. Pulmonary hypertension: a stage for ventricular interdependence?. J. Am. Coll. Cardiol. 59, 2203–2205, https://doi.org/10.1016/j.jacc.2011.12.049 (2012).

    Article  PubMed  Google Scholar 

  94. Jayasekera, G. et al. Left ventricular dysfunction and intra-ventricular dyssynchrony in idiopathic pulmonary arterial hypertension. Int J. Cardiol. 365, 131–139, https://doi.org/10.1016/j.ijcard.2022.07.032 (2022).

    Article  PubMed  CAS  Google Scholar 

  95. Richter, M. J. et al. Right ventricular dyssynchrony: from load-independent right ventricular function to wall stress in severe pulmonary arterial hypertension. Pulm. Circ. 10, 2045894020925759, https://doi.org/10.1177/2045894020925759 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Wan, C. et al. Prognostic effect of left ventricular-pulmonary arterial coupling indicator in pulmonary arterial hypertension. Int J. Cardiol. 434, 133347. https://doi.org/10.1016/j.ijcard.2025.133347 (2025).

    Article  PubMed  Google Scholar 

  97. Zani, A. et al. Congenital diaphragmatic hernia. Nat. Rev. Dis. Prim. 8, 37, https://doi.org/10.1038/s41572-022-00362-w (2022).

    Article  PubMed  Google Scholar 

  98. Altit, G., Bhombal, S., Van Meurs, K. & Tacy, T. A. Ventricular Performance is Associated with Need for Extracorporeal Membrane Oxygenation in Newborns with Congenital Diaphragmatic Hernia. J. Pediatr. 191, 28–34.e1, https://doi.org/10.1016/j.jpeds.2017.08.060 (2017).

    Article  PubMed  Google Scholar 

  99. Patel, N. et al. Early Postnatal Ventricular Dysfunction Is Associated with Disease Severity in Patients with Congenital Diaphragmatic Hernia. J. Pediatr. 203, 400–407.e1, https://doi.org/10.1016/j.jpeds.2018.07.062 (2018).

    Article  PubMed  Google Scholar 

  100. Tydén, K., Mesas Burgos, C., Jonsson, B. & Nordenstam, F. Left atrial strain in neonates with congenital diaphragmatic hernia and length of stay in pediatric intensive care unit. Front Pediatr. 12, 1404350. https://doi.org/10.3389/fped.2024.1404350 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Altit, G., Lapointe, A., Kipfmueller, F. & Patel, N. Cardiac function in congenital diaphragmatic hernia. Semin Pediatr. Surg. 33, 151438. https://doi.org/10.1016/j.sempedsurg.2024.151438 (2024).

    Article  PubMed  Google Scholar 

  102. Patel, N., Massolo, A. C., Kraemer, U. S. & Kipfmueller, F. The heart in congenital diaphragmatic hernia: Knowns, unknowns, and future priorities. Front Pediatr. 10, 890422. https://doi.org/10.3389/fped.2022.890422 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Pugnaloni, F. et al. Early Postnatal Ventricular Disproportion Predicts Outcome in Congenital Diaphragmatic Hernia. Am. J. Respir. Crit. Care Med 208, 325–328, https://doi.org/10.1164/rccm.202212-2306LE (2023).

    Article  PubMed  Google Scholar 

  104. Stressig, R. et al. Preferential streaming of the ductus venosus toward the right atrium is associated with a worse outcome despite a higher rate of invasive procedures in human fetuses with left diaphragmatic hernia. Ultraschall Med 34, 568–572, https://doi.org/10.1055/s-0032-1330702 (2013).

    Article  PubMed  CAS  Google Scholar 

  105. Massolo, A. C. et al. Ventricular Dysfunction, Interdependence, and Mechanical Dispersion in Newborn Infants with Congenital Diaphragmatic Hernia. Neonatology 116, 68–75, https://doi.org/10.1159/000499347 (2019).

    Article  PubMed  Google Scholar 

  106. Noh, C. Y. et al. Early nitric oxide is not associated with improved outcomes in congenital diaphragmatic hernia. Pediatr. Res 93, 1899–1906, https://doi.org/10.1038/s41390-023-02491-8 (2023).

    Article  PubMed  CAS  Google Scholar 

  107. Tanaka, T. et al. The evaluation of diastolic function using the diastolic wall strain (DWS) before and after radical surgery for congenital diaphragmatic hernia. Pediatr. Surg. Int 31, 905–910, https://doi.org/10.1007/s00383-015-3766-0 (2015).

    Article  PubMed  Google Scholar 

  108. Patel, N. & Kipfmueller, F. Cardiac dysfunction in congenital diaphragmatic hernia: Pathophysiology, clinical assessment, and management. Semin Pediatr. Surg. 26, 154–158, https://doi.org/10.1053/j.sempedsurg.2017.04.001 (2017).

    Article  PubMed  Google Scholar 

  109. Sehgal, A., Krishnamurthy, M. B., Clark, M. & Menahem, S. ACE inhibition for severe bronchopulmonary dysplasia - an approach based on physiology. Physiol. Rep. 6, e13821, https://doi.org/10.14814/phy2.13821 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Kluckow, M., Seri, I. & Evans, N. Functional echocardiography: an emerging clinical tool for the neonatologist. J. Pediatr. 150, 125–130, https://doi.org/10.1016/j.jpeds.2006.10.056 (2007).

    Article  PubMed  Google Scholar 

  111. Lewandowski, A. J. et al. Preterm heart in adult life: cardiovascular magnetic resonance reveals distinct differences in left ventricular mass, geometry, and function. Circulation 127, 197–206, https://doi.org/10.1161/circulationaha.112.126920 (2013).

    Article  PubMed  Google Scholar 

  112. Phad, N. S., de Waal, K., Holder, C. & Oldmeadow, C. Dilated hypertrophy: a distinct pattern of cardiac remodeling in preterm infants. Pediatr. Res. 87, 146–152, https://doi.org/10.1038/s41390-019-0568-4 (2020).

    Article  PubMed  Google Scholar 

  113. Lewandowski, A. J. et al. Association of Preterm Birth With Myocardial Fibrosis and Diastolic Dysfunction in Young Adulthood. J. Am. Coll. Cardiol. 78, 683–692, https://doi.org/10.1016/j.jacc.2021.05.053 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Leeson, P. & Lewandowski, A. J. A New Risk Factor for Early Heart Failure: Preterm Birth. J. Am. Coll. Cardiol. 69, 2643–2645, https://doi.org/10.1016/j.jacc.2017.03.574 (2017).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. John Hunter Children’s Hospital Department of Neonatology and University of Newcastle, Newcastle, NSW, Australia

    Koert de Waal

  2. University of Rochester, Rochester, New York, USA

    Irina Prelipcean

  3. Royal Hospital for Children, Department of neonatology, Glasgow, UK

    Neil Patel

Authors
  1. Koert de Waal
    View author publications

    Search author on:PubMed Google Scholar

  2. Irina Prelipcean
    View author publications

    Search author on:PubMed Google Scholar

  3. Neil Patel
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Dr. de Waal, Dr. Prelipcean, and Dr. Patel were authors of the original draft of the manuscript.

Corresponding author

Correspondence to Koert de Waal.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in studies used in this review.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Waal, K., Prelipcean, I. & Patel, N. Diastolic function in newborn infants: understanding pathophysiology, diagnosis and clinical relevance. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04561-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41390-025-04561-5

This article is cited by

Search

Advanced search

Quick links