Cardiac Disease in Childhood Cancer Survivors

Leerink, Jan M.; Baat, Esmée C de; Feijen, Elizabeth A M; Bellersen, Louise; Dalen, Elvira C. van; Grotenhuis, Heynric B.; Kapusta, Livia; Kok, Wouter E.; Loonen, Jacqueline; Pal, Heleen J H van der; Pluijm, Saskia M F; Teske, Arco J.; Mavinkurve‐Groothuis, Annelies M. C.; Merkx, Remy; Kremer, Leontien C. M.

doi:10.1016/j.jaccao.2020.08.006

Cited by 62 publications

(57 citation statements)

References 108 publications

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“…First, we did not perform a preliminary sample size calculation to plan the number of subjects to enroll in the study. However, since previous studies showed that CCSs may have a decrease in LVEF of 10% (58,59), we calculated that 6 subjects per group only might have been sufficient to have an 80% statistical power to detect as significant at two-tailed p < 0.05 a reduction of 10% in LVEF in CCS compared to healthy controls (LVEF 65.3 ± 4.4%). However, larger population may be required to better define the entity of LV impairment in CCSs.…”

Section: Limitationsmentioning

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: Limitationsmentioning

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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“…However, not all studies of long-term (>1 year) childhood cancer survivors have found female sex to be an adverse risk factor, 36–40 resulting in overall mixed conclusions regarding a sex predilection for cardiotoxicity in childhood cancer survivors. In a prospective cohort study of 514 five-year childhood cancer survivors who had received cardiotoxic therapies including anthracyclines, sex was not a risk factor for abnormal cardiac function as defined by change in LV shortening fraction (male versus female, β=0.77 [95% CI, −0.27 to 1.80]).…”

Section: Anthracyclinesmentioning

confidence: 99%

Sex-Specific Cardiovascular Risks of Cancer and Its Therapies

Wilcox

Rotz

Mullen

et al. 2022

Circulation Research

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In both cardiovascular disease and cancer, there are established sex-based differences in prevalence and outcomes. Males and females may also differ in terms of risk of cardiotoxicity following cancer therapy, including heart failure, cardiomyopathy, atherosclerosis, thromboembolism, arrhythmias, and myocarditis. Here, we describe sex-based differences in the epidemiology and pathophysiology of cardiotoxicity associated with anthracyclines, hematopoietic stem cell transplant (HCT), hormone therapy and immune therapy. Relative to males, the risk of anthracycline-induced cardiotoxicity is higher in prepubertal females, lower in premenopausal females, and similar in postmenopausal females. For autologous hematopoietic cell transplant, several studies suggest an increased risk of late heart failure in female lymphoma patients, but sex-based differences have not been shown for allogeneic hematopoietic cell transplant. Hormone therapies including GnRH (gonadotropin-releasing hormone) modulators, androgen receptor antagonists, selective estrogen receptor modulators, and aromatase inhibitors are associated with cardiotoxicity, including arrhythmia and venous thromboembolism. However, sex-based differences have not yet been elucidated. Evaluation of sex differences in cardiotoxicity related to immune therapy is limited, in part, due to low participation of females in relevant clinical trials. However, some studies suggest that females are at increased risk of immune checkpoint inhibitor myocarditis, although this has not been consistently demonstrated. For each of the aforementioned cancer therapies, we consider sex-based differences according to cardiotoxicity management. We identify knowledge gaps to guide future mechanistic and prospective clinical studies. Furthering our understanding of sex-based differences in cancer therapy cardiotoxicity can advance the development of targeted preventive and therapeutic cardioprotective strategies.

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“…Reflective of this progress, the 5-year survival for all pediatric cancer types is now >80% compared with 20% just 3 decades ago ( 12 ). Despite these advancements, survivors are at a higher risk of premature mortality and chronic diseases as a direct consequence of their cancer and their cancer therapy ( 13 ). Compared with their siblings, survivors are 10 times more likely to die from CVD and 15 times more likely to develop heart failure (HF) ( 12 , 14 , 15 , 16 ).…”

Section: Cvd In Cancer Patients and Survivorsmentioning

confidence: 99%

“…In fact, 73% of survivors will develop at least 1 chronic physical health condition, and 42% will develop a severe, life-threatening, or disabling condition or die from a chronic condition ( 12 , 17 , 18 ). Enmeshed within the advances in cancer treatment are the unintended consequences of cancer treatment–related cardiotoxicity, with notable implicated therapies including anthracyclines, radiation therapy, tyrosine kinase inhibitors, and immune therapy ( 13 ). Patients who have been treated for cancer are at increased risk of the development of CVD, including HF, coronary disease, and arrhythmias.…”

Section: Cvd In Cancer Patients and Survivorsmentioning

confidence: 99%

See 1 more Smart Citation

Cardio-Oncology

Karlstaedt

Barrett

et al. 2021

JACC: Basic to Translational Science

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Highlights Cancer cells can promote metabolic remodeling in the heart. Metabolic changes provide opportunities for novel treatment strategies to prevent heart failure and monitor disease progression through new imaging techniques. Translational biomarker and imaging studies are needed to further understand the impact of cancer cell biology on the heart.

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Cardiac Disease in Childhood Cancer Survivors

Cited by 62 publications

References 108 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

Sex-Specific Cardiovascular Risks of Cancer and Its Therapies

Cardio-Oncology

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