Tissue Doppler Imaging and Focal, Late-Onset Anthracycline-Induced Cardiovascular Disease in Long Term Survivors of Childhood Cancer: A Research Article

Rajapreyar, Prakadeshwari; Lorenzana, Adonis; Prabhu, Anuradha; Szpunar, Susan; Anne, Premchand

doi:10.7860/jcdr/2016/19652.8249

Cited by 6 publications

(5 citation statements)

References 20 publications

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“…In the absence of enlarged left atria, the ratio of mitral valve septal annular E to the early velocity as measured by tissue Doppler imaging (E') (E/E') was increased in patients with subclinical cardiovascular impairment in the current study, correlating with the amount of cumulative anthracycline exposure as a sign of subclinical diastolic dysfunction. This was also shown by others (67,(82)(83)(84) and supports the hypothesis of a progressive, restrictive-like cardiomyopathy pattern previously described in serial echocardiographic studies of long-term childhood cancer survivors treated with anthracyclines (59,74,(85)(86)(87)(88).…”

Section: Discussionsupporting

confidence: 89%

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

et al. 2020

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Background: Survivors of childhood cancer are at risk for anthracycline-and/or radiotherapy-induced cardiotoxicity. Aims: The aim of this study was to assess clinical, laboratory, and imaging parameters of subclinical cardiovascular disease in childhood cancer survivors. Methods: Patients underwent cardiopulmonary exercise test (CPET), laboratory testing, transthoracic echocardiography (TTE) with tissue doppler imaging (TDI) and speckle tracking. A subset of patients also underwent cardiovascular magnetic resonance imaging (CMR). Findings were correlated to cumulative anthracycline and exposure to mediastinal irradiation during cancer treatment. In a subgroup analysis, TTE and CMR findings were compared to data from 40 gender-and age-matched patients with childhood onset hypertrophic cardiomyopathy (HCM). Results: Cardiac evaluation was performed in 79 patients (43 males) at 11.2 ± 4.5 years after cancer treatment. Oncologic diagnosis at a median age of 12.0 years was Hodgkin lymphoma in 20, sarcoma in 17, acute leukemia in 24, relapse leukemia in 10, and others in 8 patients. Cumulative anthracycline dose exceeded 300 mg/m 2 in 28 patients. Twenty six patients also received mediastinal irradiation. Decreased peak respiratory oxygen uptake in % predicted on CPET, increased levels of N-terminal pro-brain natriuretic peptide (NTproBNP), increased global longitudinal strain on TTE speckle tracking, and diastolic Wolf et al. Cardiovascular Disease Childhood Cancer Survivors dysfunction on TDI were the most prominent findings on detailed cardiology follow-up. In contrast to HCM patients, childhood cancer survivors did not show left ventricular hypertrophy (LVPWd z-score median 0.9 vs. 2.8, p < 0.001), hyperdynamic systolic function on TTE (Ejection fraction 62 ± 7 vs. 72 ± 12%, p = 0.001), or fibrotic myocardial changes on CMR (Late gadolinium positive 0/13 vs. 13/36, p = 0.001; extracellular volume fraction 22 ± 2 vs. 28 ± 3, p < 0.001) at time of follow-up. There was no correlation between chest radiation exposure and abnormal cardiac findings. Cumulative anthracycline dose was the only significant independent predictor on multivariate analysis for any cardiovascular abnormality on follow-up (p = 0.036). Conclusion: Increasing cumulative anthracycline dose during cancer treatment correlates with subclinical cardiac dysfunction in childhood cancer survivors best detected by elevated cardiac serum biomarkers, decreased exercise capacity on CPET, and abnormalities on echocardiographic speckle tracking and TDI.

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Section: Discussionsupporting

confidence: 89%

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

et al. 2020

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“…Either the heart can grow in volume with inadequate myocardium, leading to thin-walled, high-wall stress physiology; or the heart can fail to gain volume and maintain normal thickness and wall stress at the expense of stroke volume. Diastolic dysfunction is prominent in this population [ 27 – 29 ] and severely affected patients may develop long-term complications similar to those of primary restrictive cardiomyopathy. In our cohort, we also observed the average LV mass Z-score to be low, but both the normal volume and reduced volume phenotypes were seen.…”

Section: Discussionmentioning

confidence: 99%

Left Ventricle Size Correlates with Peak Exercise Capacity in Pediatric Cancer Survivors Exposed to Anthracycline Chemotherapy

et al. 2023

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Cancer survivors exposed to anthracycline chemotherapy are at risk for developing cardiomyopathy, which may have delayed clinical manifestation. In a retrospective cross-sectional study, we evaluated the utility of cardiopulmonary exercise testing (CPET) for detecting early cardiac disease in 35 pediatric cancer survivors by examining the associations between peak exercise capacity (measured via percent predicted peak VO2) and resting left ventricular (LV) function on echocardiography and cardiac magnetic resonance imaging (cMRI). We additionally assessed the relationships between LV size on resting echocardiography or cMRI and percent predicted peak VO2 since LV growth arrest can occur in anthracycline-exposed patients prior to changes in LV systolic function. We found reduced exercise capacity in this cohort, with low percent predicted peak VO2 (62%, IQR: 53–75%). While most patients in our pediatric cohort had normal LV systolic function, we observed associations between percent predicted peak VO2 and echocardiographic and cMRI measures of LV size. These findings indicate that CPET may be more sensitive in manifesting early anthracycline-induced cardiomyopathy than echocardiography in pediatric cancer survivors. Our study also highlights the importance of assessing LV size in addition to function in pediatric cancer survivors exposed to anthracyclines.

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“…Therefore, the majority of ALL children are expected to become long-term survivors, although unfortunately, many of them are still likely to experience adverse late effects related to chemotherapies [2][3][4][5]. High incidence in cardiotoxicity is well documented in long term childhood ALL survivors who underwent anthracycline treatment, especially doxorubicin and daunorubicin [6,7]. Anthracyclines promote myocardial injury by inducing myocyte morphology and function alterations, myocardial sarcoplasmic reticulum damage, and mitochondria vacuolization which can negatively impact left ventricular (LV) function and compliance [8,9].…”

Section: Introductionmentioning

confidence: 99%

Early-Onset Myocardial and Vascular Toxicity in Childhood Acute Lymphoblastic Leukemia Survivors: The Predictive Value of the Right Heart

Muggeo¹,

Scicchitano

Muggeo³

et al. 2022

Preprint

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Purpose. Childhood acute lymphoblastic leukemia (ALL) survivors who underwent chemotherapy with anthracyclines have an increased cardiovascular risk. Few are data about right ventricle function (RV) in these patients. The aim of the study was to evaluate left and right cardiac chambers and vascular endothelial function in ALL survivors. Methods. We enrolled 54 ALL survivors and 37 healthy controls. All patients underwent auxological evaluation, blood pressure, biochemical parameters of endothelial dysfunction, flow-mediated dilatation (FMD) of the brachial artery, mean common carotid intima-media thickness (c-IMT), antero-posterior diameter of the infra-renal abdominal aorta (APAO), and echocardiographic assessment. Results. ALL subjects had significantly lower FMD (p = 0.0041), higher left (p = 0.0057) and right (p = 0.0021) TEI index as compared to controls. Tricuspid annular plane excursion (TAPSE) was 16.9 ± 1.2 mm vs 24.5 ± 3.7 mm, p < 0.0001. Cumulative anthracycline doses were related to TAPSE (r = 0.77, p < 0.001). The ROC curve analysis revealed that left and right TEI index, TAPSE, FMD showed significant association to ALL condition. TAPSE > 18 mm was the best discriminant rule to spot ALL patients (AUC: 0.966, p < 0.0001, sensibility: 100%, specificity: 89.2%). Conclusion. ALL survivors treated with anthracyclines demonstrated systo/diastolic alterations of the RV and reduced endothelial function compared with healthy controls. Although multimodality diagnostic is available, echocardiography plays pivotal role in everyday clinical practice. The early recognition of subclinical cardiac and vascular impairment is of utmost importance for the cardio-oncologist to implement strategies preventing overt cardiovascular disease.

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Tissue Doppler Imaging and Focal, Late-Onset Anthracycline-Induced Cardiovascular Disease in Long Term Survivors of Childhood Cancer: A Research Article

Cited by 6 publications

References 20 publications

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

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

Left Ventricle Size Correlates with Peak Exercise Capacity in Pediatric Cancer Survivors Exposed to Anthracycline Chemotherapy

Early-Onset Myocardial and Vascular Toxicity in Childhood Acute Lymphoblastic Leukemia Survivors: The Predictive Value of the Right Heart

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