Skip to main content

Advertisement

SpringerLink
Log in

Assessing the left atrium of childhood cancer survivors

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Survivors of childhood cancer are at risk of cancer therapy-related cardiac dysfunction (CTRCD) characterized by systolic impairment, with little known about diastolic function. Left atrial strain (LAS) is a surrogate measure of left ventricular filling. We hypothesized that survivors (1) have lower LAS versus controls, and (2) survivors exposed to higher anthracycline dosage have even lower LAS. Cross-sectional study of 45 survivors exposed to anthracyclines ≥ 1 year after chemotherapy and 45 healthy controls. Echo variables included mitral spectral and tissue Doppler, left ventricular ejection fraction (LV EF), LV dimension, LA volume, LV global longitudinal strain (GLS), and LAS. Peak strain (Ɛ) and strain rate (SR) at three phases were obtained: atrial contraction (ac), reservoir (res), and conduit (con). Two sub-analyses of cancer survivors were performed: (1) those with anthracycline dosage ≥ 250 mg/m2, and (2) those with Ɛres in the lowest quartile. On the whole, survivors had lower Ɛres and Ɛcon values. The majority of survivors had relatively normal LAS, while a subset had very low LAS values and were more likely to be older. Survivors exposed to ≥ 250 mg/m2 anthracycline also had lower Ɛres than those < 250 mg/m2. There were no differences in mitral spectral/tissue Doppler, LV dimension, left atrial volume, or GLS. A subset of childhood cancer survivors have lower LAS than their healthy counterparts, while most are essentially normal. Those exposed to higher anthracycline dosage have even lower Ɛres. Longitudinal study of LAS may prove useful in monitoring for CTRCD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

α:

Intraclass correlation coefficient

ac:

Atrial contraction

CI:

Confidence interval

con:

Conduit

CTRCD:

Cancer therapy-related cardiac dysfunction

DT:

Deceleration time

Ɛ:

Peak strain

e′:

Tissue Doppler of lateral annulus

GLS:

Global longitudinal strain

IQR:

Interquartile range

LAS:

Left atrial strain

LV EF:

Left ventricular ejection fraction

res:

Reservoir

rho:

Spearman’s correlation coefficient

SR:

Strain rate

References

  1. Howlander N, Noone AM, Krapcho M et al (2016) SEER cancer statistics review, 1975–2013. National Cancer Institute, Bethesda (MD)

    Google Scholar 

  2. Phillips SM, Padgett LS, Leisenring WM et al (2015) Survivors of childhood cancer in the United States: prevalence and burden of morbidity. Cancer Epidemiol Biomark Prev 24:653–663

    Article  Google Scholar 

  3. Mertens AC, Liu Q, Neglia JP et al (2008) Cause-specific late mortality among 5-year survivors of childhood cancer: the childhood cancer survivor study. J Natl Cancer Inst 100:1368–1379

    Article  Google Scholar 

  4. Mertens AC, Yasui Y, Neglia JP et al (2001) Late mortality experience in five-year survivors of childhood and adolescent cancer: the childhood cancer survivor study. J Clin Oncol 19:3163–3172

    Article  CAS  Google Scholar 

  5. Mulrooney DA, Yeazel MW, Kawashima T et al (2009) Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the childhood cancer survivor study cohort. BMJ 339:b4606

    Article  Google Scholar 

  6. Plana JC, Galderisi M, Barac A et al (2014) Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 15:1063–1093

    Article  Google Scholar 

  7. Children’s Oncology Group (2013) Long-term follow-up guidelines for survivors of childhood, adolescent and young adult cancers. Version 4.0. 41-44, 99-102

  8. Oeffinger KC, Mertens AC, Sklar CA et al (2006) Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 355:1572–1582

    Article  CAS  Google Scholar 

  9. Adams MJ, Lipshultz SE (2005) Pathophysiology of anthracycline- and radiation-associated cardiomyopathies: implications for screening and prevention. Pediatr Blood Cancer 44:600–606

    Article  Google Scholar 

  10. Krischer JP, Epstein S, Cuthbertson DD et al (1997) Clinical cardiotoxicity following anthracycline treatment for childhood cancer: the Pediatric Oncology Group experience. J Clin Oncol 15:1544–1552

    Article  CAS  Google Scholar 

  11. Stoodley PW, Richards DA, Hui R et al (2011) Two-dimensional myocardial strain imaging detects change in left ventricular systolic function immediately after anthracycline chemotherapy. Eur J Echocardiogr 12:945–952

    Article  Google Scholar 

  12. Neilan TG, Jassal DS, Perez-Sanz TM et al (2006) Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury. Eur Heart J 27:1868–1875

    Article  Google Scholar 

  13. Ho E, Brown A, Barrett P et al (2010) Subclinical anthracycline- and trastuzumab-induced cardiotoxicity in the long-term follow-up of asymptomatic breast cancer survivors: a speckle tracking echocardiographic study. Heart 96:701–707

    Article  CAS  Google Scholar 

  14. Ganame J, Claus P, Uyttebroeck A et al (2007) Myocardial dysfunction late after low-dose anthracycline treatment in asymptomatic pediatric patients. J Am Soc Echocardiogr 20:1351–1358

    Article  Google Scholar 

  15. Lipshultz SE, Lipsitz SR, Sallan SE et al (2005) Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J Clin Oncol 23:2629–2636

    Article  CAS  Google Scholar 

  16. Mawad W, Friedberg MK (2017) The continuing challenge of evaluating diastolic function by echocardiography in children. Curr Opin Cardiol 1:93–100

    Article  Google Scholar 

  17. Cameli M, Mandoli GE, Loiacono F, Dini FL, Henein M, Mondillo S (2016) Left atrial strain: a new parameter for assessment of left ventricular filling pressure. Heart Fail Rev 21:65–76

    Article  Google Scholar 

  18. Cameli M, Lisi M, Mondillo S et al (2010) Left atrial longitudinal strain by speckle tracking echocardiography correlates well with left ventricular filling pressures in patients with heart failure. Cardiovasc Ultrasound 8:14

    Article  Google Scholar 

  19. Cameli M, Sparla S, Losito M et al (2016) Correlation of left atrial strain and Doppler measurements with invasive measurement of left ventricular end diastolic pressure in patients stratified for different values of ejection fraction. Echocardiography 33:398–405

    Article  Google Scholar 

  20. Feijen EAM, Leisenring WM, Stratton KL et al (2019) Derivation of anthracycline and anthraquinone equivalence ratios to doxorubicin for late-onset cardiotoxicity. JAMA Oncol 5:864–871

    Article  Google Scholar 

  21. Badano LP, Kolias TJ, Muraru D, Abraham TP, Aurigemma G, Edvardsen T et al (2018) Standardization of left atrial, right ventricular, and right atrial deformation imaging using two-dimensional speckle tracking echocardiography: a consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. Eur H J Cardiovasc Imaging 19:591–600

    Article  Google Scholar 

  22. Hayashi S, Yamada H, Bando M et al (2015) Optimal analysis of left atrial strain by speckle tracking echocardiography: P-wave versus R-wave trigger. Echocardiography 32:1241–1249

    Article  Google Scholar 

  23. Loar RW, Pignatelli RH, Morris SA et al (2020) Left atrial strain correlates with elevated filling pressures in pediatric heart transplantation recipients. J Am Soc Echocardiogr 33:504–511

    Article  Google Scholar 

  24. Yeh J, Aiyagari R, Gajarski RJ, Zamberlan MC, Lu JC (2015) Left atrial deformation predicts pulmonary capillary wedge pressure in pediatric heart transplant recipients. Echocardiography 32:535–540

    Article  Google Scholar 

  25. Santos ABS, Roca GQ, Clagget B et al (2016) Prognostic relevance of left atrial dysfunction in heart failure with preserved ejection fraction. Circ Heart Fail 9:e002763

    Article  CAS  Google Scholar 

  26. Sanchis L, Gabrielli L, Andrea R et al (2015) Left atrial dysfunction relates to symptom onset in patients with heart failure and preserved left ventricular ejection fraction. Eur Heart J Cardiovasc Imaging 16:62–67

    Article  Google Scholar 

  27. Ommen SR, Nishimura RA, Appleton CP et al (2000) Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 102:1788–1794

    Article  CAS  Google Scholar 

  28. Singh A, Medvedofsky D, Mediratta A et al (2019) Peak left atrial strain as a single measure for the non-invasive assessment of left ventricular filling pressures. Int J Cardiovasc Imaging 35:23–32

    Article  Google Scholar 

  29. Gottdiener JS, Kitzman DW, Aurigemma GP, Arnold AM, Manolio TA (2006) Left atrial volume, geometry, and function in systolic and diastolic heart failure of persons ≥ 65 years of age. Am J Cardiol 97:83–89

    Article  Google Scholar 

  30. Miyoshi H, Oishi Y, Mizuguchi Y et al (2013) Early predictors of alterations in left atrial structure and function related to left ventricular dysfunction in asymptomatic patients with hypertension. J Am Soc Hypertens 7:206–215

    Article  Google Scholar 

  31. Machino-Ohtsuka T, Seo Y, Tada H et al (2011) Left atrial stiffness relates to left ventricular diastolic dysfunction and recurrence after pulmonary vein isolation for atrial fibrillation. J Cardiovasc Electrophysiol 22:999–1006

    Article  Google Scholar 

  32. Kutty S, Padiyath A, Li L, Peng Q, Rangamani S, Schuster A et al (2013) Functional maturation of left and right atrial systolic and diastolic performance in infants, children, and adolescents. J Am Soc Echocardiogr 26:398–409

    Article  Google Scholar 

  33. Sabatino J, Di Salvo G, Prota C et al (2019) Left atrial strain to identify diastolic dysfunction in children with cardiomyopathies. J Clin Med 8:e1243

    Article  Google Scholar 

  34. Armstrong GT, Liu Q, Yasui Y et al (2009) Late mortality among 5-year survivors of childhood cancer: a summary from the childhood cancer survivor study. J Clin Oncol 27:2328–2338

    Article  CAS  Google Scholar 

  35. Patel NR, Chyu CK, Satou GM, Halnon NJ, Nguyen KL (2018) Left atrial function in children and young adult survivors treated with anthracycline. Echocardiography 35:1649–1656

    Article  Google Scholar 

  36. Li VW, Lai CT, Liu AP, Cheuk DK, Cheung Y (2017) Left atrial mechanics and integrated calibrated backscatter in anthracycline-treated long-term survivors of childhood cancers. Ultrasound Med Biol 43:1897–1905

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the staff at the Texas Children’s Hospital Cardiovascular Clinical Research Core for the help in data collection and analysis for this project.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Pediatric Cardiology, Cook Children’s Medical Center, Fort Worth, TX, USA

    Robert W. Loar

  2. Pediatric Cardiology, Baylor College of Medicine/Texas Children’s Hospital, Houston, TX, USA

    John L. Colquitt, Asela M. Liu, Hari P. Tunuguntla, Christian Lilje & Ricardo H. Pignatelli

  3. Pediatric Hematology/Oncology, Baylor College of Medicine/Texas Children’s Hospital, Houston, TX, USA

    Nino C. Rainusso & M. Monica Gramatges

  4. Pediatric Cardio-Oncology Program, Baylor College of Medicine/Texas Children’s Hospital, Houston, TX, USA

    Nino C. Rainusso, M. Monica Gramatges, Hari P. Tunuguntla, Christian Lilje & Ricardo H. Pignatelli

  5. Pediatric Cardiology, Seattle Children’s Hospital, Anchorage, AK, USA

    Cory V. Noel

Authors
  1. Robert W. Loar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John L. Colquitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nino C. Rainusso
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Monica Gramatges
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Asela M. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cory V. Noel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hari P. Tunuguntla
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christian Lilje
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ricardo H. Pignatelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors listed made significant contributions to all of the following areas: (1) the conception and design of the study, acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version submitted.

Corresponding author

Correspondence to Robert W. Loar.

Ethics declarations

Conflict of interest

We have no potential conflict of interest.

Additional information

Publisher's Note

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

Electronic supplementary material

Below is the link to the electronic supplementary material.

10554_2020_1970_MOESM1_ESM.docx

Supplementary file1 Supplemental Table: Comparisons of cancer survivors with Ɛres in the top 3 quartiles (n = 34) versus normal controls. (DOCX 12 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Loar, R.W., Colquitt, J.L., Rainusso, N.C. et al. Assessing the left atrium of childhood cancer survivors. Int J Cardiovasc Imaging 37, 155–162 (2021). https://doi.org/10.1007/s10554-020-01970-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-020-01970-x

Keywords

Search

Navigation