Childhood Cancer Survivors Have Impaired Strain-Derived Myocardial Contractile Reserve by Dobutamine Stress Echocardiography

Abnormal left ventricular contractile reserve (LVCR) is associated with adverse cardiac outcomes in different patient cohorts and might be useful in the detection of cardiomyopathy in childhood cancer survivors (CCS) after cardiotoxic treatment. The aim of this study was to evaluate LVCR by dobutamine stress echocardiography (DSE) combined with measures of myocardial strain in CCS previously treated with anthracyclines (AC). Fifty-three CCS (age 25.34 ± 2.44 years, 35 male) and 53 healthy controls (age 24.40 ± 2.40 years, 32 male) were included. Subjects were examined with echocardiography at rest, at low-dose (5 micrograms/kg/min), and at high-dose (40 micrograms/kg/min) dobutamine infusion. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), strain rate (GSR), and early diastolic strain rate (GEDSR) at different DSE phases were used as measures of LVCR. The mean follow-up time among CCS was 15.8 ± 5.8 years. GLS, GSR, and LVEF were lower at rest in CCS compared to controls (p ≤ 0.03). LVEF was within the normal range in CCS. ΔGLS, ΔGSR, and ΔGEDSR but not ΔLVEF were lower in CCS compared to controls after both low- (p ≤ 0.048) and high-dose dobutamine infusion (p ≤ 0.023). We conclude that strain measures during low-dose DSE detect impaired myocardial contractile reserve in young CCS treated with AC at 15-year follow-up. Thus, DSE may help identify asymptomatic CCS at risk for heart failure and allows for tailored follow-up accordingly.

[1]  M. Hudson,et al.  Delphi Panel Consensus Recommendations for Screening and Managing Childhood Cancer Survivors at Risk for Cardiomyopathy , 2022, JACC. CardioOncology.

[2]  C. Apitz,et al.  Left Ventricular Strain Analysis During Submaximal Semisupine Bicycle Exercise Stress Echocardiography in Childhood Cancer Survivors , 2022, Journal of the American Heart Association.

[3]  T. Wakatsuki,et al.  Association between cardiovascular risk factors and left ventricular strain distribution in patients without previous cardiovascular disease , 2022, Journal of Echocardiography.

[4]  A. Nasis,et al.  Left ventricular contractile reserve as a determinant of adverse clinical outcomes: a systematic review , 2022, Internal medicine journal (Print).

[5]  I. Øra,et al.  Characterization of Cardiac, Vascular, and Metabolic Changes in Young Childhood Cancer Survivors , 2021, Frontiers in Pediatrics.

[6]  I. Kardys,et al.  Detection of Subclinical Cardiovascular Disease by Cardiovascular Magnetic Resonance in Lymphoma Survivors , 2021, JACC. CardioOncology.

[7]  L. Constine,et al.  Cardiometabolic risk in childhood cancer survivors: a report from the Children's Oncology Group. , 2021, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[8]  T. Ojala,et al.  Cardiac Function After Cardiotoxic Treatments for Childhood Cancer—Left Ventricular Longitudinal Strain in Screening , 2021, Frontiers in Cardiovascular Medicine.

[9]  J. Daoud,et al.  Subclinical left ventricle impairment following breast cancer radiotherapy: Is there an association between segmental doses and segmental strain dysfunction? , 2021, International journal of cardiology.

[10]  P. Nihoyannopoulos,et al.  Echocardiographic Longitudinal Strain Analysis in Heart Failure: Real Usefulness for Clinical Management Beyond Diagnostic Value and Prognostic Correlations? A Comprehensive Review , 2021, Current Heart Failure Reports.

[11]  P. Lamendola,et al.  Cardiac Surveillance for Early Detection of Late Subclinical Cardiac Dysfunction in Childhood Cancer Survivors After Anthracycline Therapy , 2021, Frontiers in Oncology.

[12]  M. Hersberger,et al.  Advanced Imaging and New Cardiac Biomarkers in Long-term Follow-up After Childhood Cancer , 2021, Journal of pediatric hematology/oncology.

[13]  C. D. de Korte,et al.  Asymptomatic systolic dysfunction on contemporary echocardiography in anthracycline-treated long-term childhood cancer survivors: a systematic review , 2021, Journal of Cancer Survivorship.

[14]  M. H. van den Berg,et al.  Health-Related Quality of Life in European Childhood Cancer Survivors: Protocol for a Study Within PanCareLIFE , 2021, JMIR research protocols.

[15]  H. Grotenhuis,et al.  Cardiac Disease in Childhood Cancer Survivors , 2020, JACC. CardioOncology.

[16]  C. D. de Korte,et al.  Myocardial 2D Strain During Long-Term (>5 Years) Follow-Up of Childhood Survivors of Acute Lymphoblastic Leukemia Treated With Anthracyclines. , 2020, The American journal of cardiology.

[17]  C. Wolf,et al.  Subclinical Cardiac Dysfunction in Childhood Cancer Survivors on 10-Years Follow-Up Correlates With Cumulative Anthracycline Dose and Is Best Detected by Cardiopulmonary Exercise Testing, Circulating Serum Biomarker, Speckle Tracking Echocardiography, and Tissue Doppler Imaging , 2020, Frontiers in Pediatrics.

[18]  E. Hirsch,et al.  Mechanisms of Anthracycline-Induced Cardiotoxicity: Is Mitochondrial Dysfunction the Answer? , 2020, Frontiers in Cardiovascular Medicine.

[19]  R. Daly,et al.  The Utility of Cardiac Reserve for the Early Detection of Cancer Treatment-Related Cardiac Dysfunction: A Comprehensive Overview , 2020, Frontiers in Cardiovascular Medicine.

[20]  R. Luepker,et al.  Exercise Intolerance, Mortality, and Organ System Impairment in Adult Survivors of Childhood Cancer. , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  P. Nathan,et al.  Echocardiographic Assessment of Cardiac Function in Pediatric Survivors of Anthracycline-Treated Childhood Cancer. , 2019, Circulation. Cardiovascular imaging.

[22]  E. Oikonomou,et al.  Assessment of Prognostic Value of Left Ventricular Global Longitudinal Strain for Early Prediction of Chemotherapy-Induced Cardiotoxicity: A Systematic Review and Meta-analysis. , 2019, JAMA cardiology.

[23]  M. H. van den Berg,et al.  Risk and Temporal Changes of Heart Failure Among 5‐Year Childhood Cancer Survivors: a DCOG‐LATER Study , 2018, Journal of the American Heart Association.

[24]  Patrizio Lancellotti,et al.  Normal Global Longitudinal Strain: An Individual Patient Meta-analysis. , 2019, JACC. Cardiovascular imaging.

[25]  S. Garwicz,et al.  A population based pediatric oncology registry in Southern Sweden: the BORISS registry , 2018, European Journal of Epidemiology.

[26]  P. Nathan,et al.  Cardiovascular Disease in Survivors of Childhood Cancer: Insights Into Epidemiology, Pathophysiology, and Prevention. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  P. Nathan,et al.  Dynamic Myocardial Response to Exercise in Childhood Cancer Survivors Treated with Anthracyclines , 2018, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[28]  B. He,et al.  Subclinical Anthracycline-Induced Cardiotoxicity in the Long - Term Follow-Up of Lymphoma Survivors: A Multi-Layer Speckle Tracking Analysis , 2018, Arquivos brasileiros de cardiologia.

[29]  Eugenio Picano,et al.  The clinical use of stress echocardiography in non-ischaemic heart disease: recommendations from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. , 2016, European heart journal cardiovascular Imaging.

[30]  Richard B. Thompson,et al.  Impaired Left Ventricular Reserve in Childhood Cancer Survivors Treated With Anthracycline Therapy , 2016, Pediatric blood & cancer.

[31]  P. Nathan,et al.  Reduction in Late Mortality among 5-Year Survivors of Childhood Cancer. , 2016, The New England journal of medicine.

[32]  Erwan Donal,et al.  Value of exercise echocardiography in heart failure with preserved ejection fraction: a substudy from the KaRen study. , 2015, European heart journal cardiovascular Imaging.

[33]  L. Tryggvadottir,et al.  Cardiovascular disease in Adult Life after Childhood Cancer in Scandinavia: A population‐based cohort study of 32,308 one‐year survivors , 2015, International journal of cancer.

[34]  James D. Thomas,et al.  Comprehensive Echocardiographic Detection of Treatment-Related Cardiac Dysfunction in Adult Survivors of Childhood Cancer: Results From the St. Jude Lifetime Cohort Study. , 2015, Journal of the American College of Cardiology.

[35]  P. Lähteenmäki,et al.  Late mortality among 5‐year survivors of early onset cancer: A population‐based register study , 2015, International journal of cancer.

[36]  A. Mertens,et al.  Assessing anthracycline‐treated childhood cancer survivors with advanced stress echocardiography , 2015, Pediatric blood & cancer.

[37]  P. Nathan,et al.  Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. , 2015, The Lancet. Oncology.

[38]  Kevin C Oeffinger,et al.  Individual prediction of heart failure among childhood cancer survivors. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  N. Winick,et al.  Subclinical cardiotoxicity in childhood cancer survivors exposed to very low dose anthracycline therapy , 2015, Pediatric blood & cancer.

[40]  Victor Mor-Avi,et al.  Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. , 2015, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[41]  S. Kutty,et al.  Changes in left ventricular longitudinal strain with anthracycline chemotherapy in adolescents precede subsequent decreased left ventricular ejection fraction. , 2012, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[42]  R H Hruban,et al.  Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. , 2000, The New England journal of medicine.

[43]  J. Seward,et al.  Normal stroke volume and cardiac output response during dobutamine stress echocardiography in subjects without left ventricular wall motion abnormalities. , 1995, The American journal of cardiology.

[44]  Nathaniel Reichek,et al.  Stress echocardiography , 1993, Current opinion in cardiology.