Natural history of myocardial deformation in children, adolescents, and young adults exposed to anthracyclines: Systematic review and meta‐analysis

Tuzovic, Mirela; Wu, Pei-Tzu; Kianmahd, Samuel; Nguyen, Kim‐Lien

doi:10.1111/echo.13871

Cited by 31 publications

(19 citation statements)

References 57 publications

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“…Unlike conventional LVSF and LVEF, which are limited to one plane, strain can be measured in three planes, providing a better determination of cardiac function. Previous studies provided evidence that strain abnormalities can be seen early despite preserved LVEF by conventional echo measures, identifying cardiac involvement in CCSs prior to the development of overt systolic dysfunction (43,(46)(47)(48)(49)(50)(51)(52)(53)(54). However, a more recent multicenter study of cardiac strain in a large cohort of pediatric CCSs found only mild differences in parameters of longitudinal strain between patients and healthy controls, with most CCSs (92.3%) having longitudinal strain values within the normal range.…”

Section: Speckle Tracking Imaging and 3d Echocardiographymentioning

confidence: 99%

Cardiac Surveillance for Early Detection of Late Subclinical Cardiac Dysfunction in Childhood Cancer Survivors After Anthracycline Therapy

et al. 2021

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BackgroundIn childhood cancer survivors (CCSs) anthracycline-related cardiotoxicity is an important cause of morbidity and late mortality, but the optimal modality of cardiac surveillance still remains to be defined. The aim of this study was to assess whether non-invasive echocardiography-based functional cardiac measures can detect early subclinical myocardial changes in long-term pediatric cancer survivors who received anthracycline therapy.MethodsTwenty anthracycline-treated long-term CCSs and 20 age, sex, and body surface area matched healthy controls were enrolled in this study. Among cancer survivors, mean age at diagnosis was 6.5 ± 4.4 years, and the mean cumulative anthracycline dose was 234.5 ± 87.4 mg/m2. All subjects underwent a comprehensive functional echocardiographic protocol study including two-dimensional echocardiography (2D Echo), tissue Doppler imaging (TDI), speckle tracking (STE) and three-dimensional echocardiography (3D Echo). Patients were studied at a mean follow-up time of 6.5 ± 2.8 years from the end of therapy.ResultsNo significant differences in two-dimensional left ventricle ejection fraction (LVEF), diastolic parameters and speckle tracking (STE)-derived myocardial strain were observed between patients treated with anthracyclines and controls. Myocardial performance index was significantly prolonged (p = 0.005) and three-dimensional LVEF was significantly reduced (p = 0.002) in CCSs compared to controls, even though most values were within the normal range. There were no significant correlations between 2D, STE, and 3D echocardiographic parameters and age at diagnosis or duration of follow-up. No significant differences in echocardiographic parameters were found when stratifying cancer patients according to established risk factors for anthracycline cardiomyopathy.ConclusionsThis study found significantly reduced three-dimensional LVEF in CCSs compared with controls, despite no significant differences in two-dimensional LVEF and longitudinal strain values. These findings suggest that long-term CCSs who had received anthracycline therapy may be found to have subclinical features of myocardial dysfunction. However, further studies are needed to demonstrate the validity of new imaging techniques, including STE and 3D Echo, to identify patients at risk for cardiomyopathy in the long-term follow-up of CCSs.

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Section: Speckle Tracking Imaging and 3d Echocardiographymentioning

confidence: 99%

Cardiac Surveillance for Early Detection of Late Subclinical Cardiac Dysfunction in Childhood Cancer Survivors After Anthracycline Therapy

et al. 2021

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“…Advanced imaging modalities such as tissue characterization by cardiac magnetic resonance imaging 46,47 and echocardiography-derived myocardial deformation imaging (strain) have been used to detect subclinical cardiac dysfunction in populations at risk for heart failure (eg, after myocardial infarction). 48,49 When used in conjunction with blood biomarkers of cardiac injury and remodeling, these imaging biomarkers may be especially helpful for patients with cancer with borderline LV systolic function. To date, routine use of blood and imaging biomarkers in the asymptomatic oncology population remains limited primarily because of a lack of data to support improvement in cardiac and oncology outcomes.…”

Section: Undertake Appropriate Early Screening and Cardiovascular Manmentioning

confidence: 99%

Optimizing Cardiovascular Care in Children With Acute Myeloid Leukemia to Improve Cancer-Related Outcomes

Armenian

Ehrhardt

2019

JCO

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The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 14-year-old African American female presented with fatigue, easy bruising, and fever. On examination, she had scattered bruising, lymphadenopathy, and hepatosplenomegaly. Laboratory evaluation revealed pancytopenia with peripheral blasts, and acute myeloid leukemia (AML; French-American-British M2, t[8;21][q22;q22.1]) was diagnosed on bone marrow biopsy. A baseline echocardiogram revealed normal left ventricular (LV) systolic function (ejection fraction [EF], 60%; shortening fraction [SF], 32%), and conventional chemotherapy was initiated that consisted of two cycles of remission induction (cytarabine, etoposide, and daunorubicin [50 mg/m2 × 3 days per cycle]) followed by intensification 1 (high-dose cytarabine and etoposide), intensification 2 (high-dose cytarabine and mitoxantrone [12 mg/m2/dose daily; four total doses]), and intensification 3 (high-dose cytarabine and l-asparaginase). Of note, an echocardiogram was not repeated before the start of intensification 1. During intensification 1, the patient developed Streptococcus viridans sepsis, which required 4 days in the intensive care unit with antimicrobial and inotropic support. Repeat echocardiogram after recovery from the sepsis episode demonstrated low-normal LV systolic function (EF, 53%; SF, 27%), and she subsequently began intensification 2. On day 3 of intensification 2, the patient developed afebrile tachypnea, tachycardia, and an increasing oxygen requirement. Chest x-ray revealed cardiomegaly and pulmonary vascular congestion. Cardiac troponins were normal, whereas N-terminal pro B-type natriuretic peptide was 10 times the upper limit of normal. Repeat echocardiogram showed an enlarged LV with moderate to severely depressed LV function (EF, 28%; SF, 14%). Day 4 mitoxantrone was omitted and a cardiology consult obtained.

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“…[22][23][24][25] Besides gender, age remains to be another risk factor; people at extremes of ages are more susceptible to doxorubicin-induced cardiotoxicity. [26][27][28] Co-administration of other cardiotoxic drug, simultaneous mediastinal radiotherapy, and a large dose of doxorubicin can also increase the chance of developing doxorubicin-induced cardiotoxicity. 22 Presence of other comorbidities like hypertension, diabetes, co-existing cardiac disease, liver disease might increase the risk of doxorubicin-induced cardiotoxicity.…”

Section: Doxorubicin-induced Cardiotoxicitymentioning

confidence: 99%

“…29,30 The most severe cases of cardiotoxicity due to doxorubicin is seen in cancer survivors of the pediatric age group as this side effect usually do not become apparent years after stoppage of doxorubicin. 26 It has been estimated that around 60% of pediatric cancer patients receive anthracycline group of drugs and eventually 10% of them will develop doxorubicin-induced cardiotoxicity in the next 15 years. 31 Difference in onset of doxorubicin-induced cardiotoxicity has suggested that there might be different underlying molecular mechanism involved ( Table 1).…”

Section: Doxorubicin-induced Cardiotoxicitymentioning

confidence: 99%

Major obstacles to doxorubicin therapy: Cardiotoxicity and drug resistance

Al-malky

Harthi

Osman

2019

J Oncol Pharm Pract

122

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Background Doxorubicin is one of the most commonly prescribed and time-tested anticancer drugs. Although being considered as a first line drug in different types of cancers, the two main obstacles to doxorubicin therapy are drug-induced cardiotoxicity and drug resistance. Method The study utilizes systemic reviews on publications of previous studies obtained from scholarly journal databases including PubMed, Medline, Ebsco Host, Google Scholar, and Cochrane. The study utilizes secondary information obtained from health organizations using filters and keywords to sustain information relevancy. The study utilizes information retrieved from studies captured in the peer-reviewed journals on “doxorubicin-induced cardiotoxicity” and “doxorubicin resistance.” Discussion and results The exact mechanisms of cardiotoxicity are not known; various hypotheses are studied. Doxorubicin can lead to free radical generation in various ways. The commonly proposed underlying mechanisms promoting doxorubicin resistance are the expression of multidrug resistance proteins as well as other causes. Conclusion In this review, we have described the major obstacles to doxorubicin therapy, doxorubicin-induced cardiotoxicity as well as the mechanisms of cancer drug resistance and in following the treatment failures.

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Natural history of myocardial deformation in children, adolescents, and young adults exposed to anthracyclines: Systematic review and meta‐analysis

Abstract: There are significant abnormalities in GLS and GCS following anthracycline therapy acutely and late after treatment. The prognostic value of these strain abnormalities warrants further investigation.

Cited by 31 publications

References 57 publications

Cardiac Surveillance for Early Detection of Late Subclinical Cardiac Dysfunction in Childhood Cancer Survivors After Anthracycline Therapy

Cardiac Surveillance for Early Detection of Late Subclinical Cardiac Dysfunction in Childhood Cancer Survivors After Anthracycline Therapy

Optimizing Cardiovascular Care in Children With Acute Myeloid Leukemia to Improve Cancer-Related Outcomes

Major obstacles to doxorubicin therapy: Cardiotoxicity and drug resistance

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