Detection Of Anthracycline-induced Cardiotoxicity Research Articles

An image processing tool for the detection of anthracycline-induced cardiotoxicity by evaluating the myocardial metabolic activity in [18F]FDG PET/CT

PurposeChemotherapy-induced cardiotoxicity is one of the main complications during and after cancer treatment. While echocardiography is the most used technique in clinical practice to evaluate left ventricular (LV) dysfunction, a multimodal approach is preferred for the early detection of anthracycline-induced cardiotoxicity. In this paper, an image processing tool allowing the qualitative and quantitative analysis of myocardial metabolic activity by [18F]fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET/CT) images, acquired routinely during and after cancer treatment, is presented.MethodsThe methodology is based on cardiac single photon emission computed tomography image processing protocols used in clinical practice. LV polar maps are created, and quantitative regional values are calculated. The tool was validated in a study group of 24 patients with Hodgkin or non-Hodgkin lymphoma (HL and NHL, respectively) treated with anthracyclines. Staging, interim and end-of-treatment [18F]FDG PET/CT images were acquired and the presented tool was used to extract the quantitative metrics of LV metabolic activity.ResultsResults show an overall increase of metabolic activity in the interim PET image acquired while on treatment compared to staging PET, which then decreased in the end-of-treatment scan. Positive correlation coefficients between staging and interim scans, and negative correlation coefficients between interim and end-of-treatment scans also support this finding. Metabolic changes occur predominantly in the septal region.ConclusionThe proposed methodology and presented software solution provides the capability to assess quantitatively myocardial metabolism acquired by routine [18F]FDG PET/CT scanning during cancer treatment for evaluating anthracycline-induced cardiotoxicity. The [18F]FDG PET/CT septal-lateral uptake ratio is proposed as a new quantitative measure of myocardial metabolism.

Detection of anthracycline-induced cardiotoxicity using perfusion-corrected 99mTc sestamibi SPECT

By the time cardiotoxicity-associated cardiac dysfunction is detectable by echocardiography it is often beyond meaningful intervention. 99mTc-sestamibi is used clinically to image cardiac perfusion by single photon emission computed tomography (SPECT) imaging, but as a lipophilic cation its distribution is also governed by mitochondrial membrane potential (ΔΨm). Correcting scans for variations in perfusion (using a ΔΨm-independent perfusion tracer such as (bis(N-ethoxy-N-ethyldithiocarbamato)nitrido 99mTc(V)) (99mTc-NOET) could allow 99mTc-sestamibi to be repurposed to specifically report on ΔΨm as a readout of evolving cardiotoxicity. Isolated rat hearts were perfused within a γ-detection apparatus to characterize the pharmacokinetics of 99mTc-sestamibi and 99mTc-NOET in response to mitochondrial perturbation by hypoxia, ionophore (CCCP) or doxorubicin. All interventions induced 99mTc-sestamibi washout; hypoxia from 24.9 ± 2.6% ID to 0.4 ± 6.2%, CCCP from 22.8 ± 2.5% ID to −3.5 ± 3.1%, and doxorubicin from 23.0 ± 2.2% ID to 17.8 ± 0.7, p < 0.05. Cardiac 99mTc-NOET retention (34.0 ± 8.0% ID) was unaffected in all cases. Translating to an in vivo rat model, 2 weeks after bolus doxorubicin injection, there was a dose-dependent loss of cardiac 99mTc-sestamibi retention (from 2.3 ± 0.3 to 0.9 ± 0.2 ID/g with 10 mg/kg (p < 0.05)), while 99mTc-NOET retention (0.93 ± 0.16 ID/g) was unaffected. 99mTc-NOET therefore traps in myocardium independently of the mitochondrial perturbations that induce 99mTc-sestamibi washout, demonstrating proof-of-concept for an imaging approach to detect evolving cardiotoxicity.

Relationship of promising methods in the detection of anthracycline-induced cardiotoxicity in breast cancer patients.

Purpose It remains challenging to identify patients at risk of anthracycline-induced cardiotoxicity. To better understand the different risk-stratifying approaches, we evaluated 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy and its interrelationship with conventional echocardiography, 2D strain imaging and several biomarkers.MethodsWe performed 123I-mIBG scintigraphy, conventional and strain echocardiography and biomarker (NT-proBNP, TNF-α, galectin-3, IL-6, troponin I, ST-2 and sFlt-1) assessment in 59 breast cancer survivors 1 year after anthracycline treatment. Interobserver and intermethod variability was calculated on planar and SPECT 123I-mIBG scintigraphy, using the heart/mediastinum (H/M) ratio and washout (WO). Pearson’s r and multivariate analyses were performed to identify correlations and independent predictors of 123I-mIBG scintigraphy results.ResultsDelayed planar anterior whole-heart ROI (WH) H/M ratios and WO were the most robust 123I-mIBG parameters. Significant correlations were observed between 123I-mIBG parameters and several conventional echo parameters, global longitudinal and radial strain (GLS and GRS) and galectin-3. The highest Pearson’s r was observed between delayed H/M ratio and GRS (Pearson’s r 0.36, p = 0.01). Multivariate analysis showed that GRS was the only independent predictor of the delayed WH H/M ratio (p = 0.023).ConclusionThe delayed planar H/M ratio is the most robust 123I-mIBG parameter. It correlates with several conventional echocardiographic parameters, GLS, GRS and galectin-3. Of these, only GRS predicts the H/M ratio.

Applications of global left ventricular myocardial strain in detection of anthracycline-induced cardiotoxicity in breast cancer survivors with postoperative chemotherapy

Objective To assess the clinical significance of three-dimensional speckle tracking imaging (3D-STI) in the evaluation of left ventricular myocardial function in breast cancer survivors with postoperative anthracycline-based chemotherapy.Methods A total of 51 breast cancer survivors with postoperative anthracycline-based chemotherapy were recruited and 31 female healthy volunteers as the controls.Conventional echocardiography and 3D-STI derived parameters [including global longitudinal strain (GLS) and global area strain (GAS)] were measured before and at 3 and 6 anthracycline-based chemotherapeutic cycles.The receiver operating characteristics (ROC) curve was constructed to determine optimal sensitivity and specificity of 3ID-STI derived parameters for the prediction of future cardiotoxicity.Results In comparison with the controls and baseline cases,GLS and GAS deteriorated significantly (P ＜ 0.05 for both).No statistical difference in GCS and conventional parameters showed before and after the initiation of chemotherapy (P ＜0.05,respectively).The ROC curves showed that GAS as the best 3D-STI predictor of patients who develop cardiotoxicity during the follow-up.The area under ROC(AUC) of GAS was 0.894,and its optimal cut-off value was-28.4％,with a specificity of 88.0％ and a sensitivity of 82.9％.AUC of GLS was 0.802,and its optimal cut-off value was-14.3％,with a specificity of 62.0％ and a sensitivity of 85.4％.Conclusions Early decreases in GAS and GLS based on 3D-STI may allow the prediction of subsequent cardiotoxic development accurately in breast cancer survivors with postoperative anthracycline-based chemotherapy. Key words: Echocardiography; Breast neoplasms; Ventricular function, left; Athracyclines; Cardiotoxins ; Speckle tracking imaging

Early Detection of Anthracycline-Induced Cardiotoxicity in Long-Term Survivors of Acute Lymphoblastic Leukemia Treated with Low Cumulative Dose.

We investigated the left ventricular (LV) function, using for the first time strain (S) and strain rate (SR) imaging, in long-term survivors affected by acute lymphoblastic leukemia treated with a low cumulative dose of anthracyclines, and in presence of a normal global LV systolic and diastolic function. A total of 21 were enrolled in the study. The mean cumulative dose of anthracylines was 180 mg/m2 (range: 120-210 mg/m2). As control group 21 age-sex matched healthy subjects were included. Radial S (17 ± 3% vs. 55 ± 6%, P < 0.0001) and SR (2.1 ± 0.3 vs. 3.0 ± 0.8 1\\s, P < 0.0001), assessed on the midsegment of the posterior wall from the parasternal views were significantly reduced when compared with controls. Conversely, myocardial performance index was not able to discriminate between patients and controls. In this preliminary study, the myocardial deformation indices appear to be a more sensitive noninvasive technique for detecting subclinical LV dysfunction than other echocardiographic measurements.

Abstract 2435: The Role of Myocardial Longitudinal Strain in Monitoring Subclinical Heart Failure in Survivors of Childhood Cancer

Objectives: Previous studies have demonstrated that myocardial longitudinal strain and strain rate is decreased in asymptomatic patients treated with anthracyclines. In this study, the relation between global myocardial longitudinal strain, conventional echocardiographic parameters, NT-pro-BNP levels, cumulative anthracycline dosage and follow up duration was investigated in a large group of asymptomatic long term survivors of childhood cancer. Methods: 79 asymptomatic survivors (45% children) underwent a detailed echocardiographic examination for obtaining conventional parameters and global myocardial longitudinal strain values in 4-chamber view. In addition to this, we collected blood samples for NT-pro-BNP estimation. Results: the survivors had a mean age of 20 years (range: 6 –37 years), a mean follow up duration of 14 years (range 5–27 years) and a mean cumulative anthracycline dose of 240 mg/m 2 (range 50 –524 mg/m 2 ). Reduced global myocardial longitudinal strain was significantly related to an EF&lt;55% (p&lt;0.001) and to reduced left ventricular posterior wall thickness in diastole indexed by body surface area (LVPWd/BSA) (p&lt;0.003). Reduced myocardial global longitudinal strain was not related to abnormal NT-pro-BNP levels, follow up duration and cumulative anthracycline dosage. Conclusion: reduced global myocardial longitudinal strain is related to subclinical heart failure, e.g. abnormal EF and reduced LVPWd/BSA in asymptomatic survivors of childhood cancer. The role of myocardial strain in the early detection of anthracycline-induced cardiotoxicity needs to be explored by further longitudinal prospective studies.

Role of heart rate variability for early detection of anthracycline-induced cardiotoxicity and prediction of reduction in left ventricular ejection fraction

Role of heart rate variability for early detection of anthracycline-induced cardiotoxicity and prediction of reduction in left ventricular ejection fraction

THE ROLE OF BIOMARKERS IN THE EARLY DETECTION OF ANTHRACYCLINE-INDUCED CARDIOTOXICITY IN CHILDREN: A Review of the Literature

Anthracycline-induced cardiotoxicity can cause serious health problems for an increasing number of children surviving childhood malignancies. Early detection of cardiac failure is critically important for the prevention and management of anthracycline-induced cardiotoxicity. The aim of this research was to determine the role of biomarkers in the early detection of anthracycline-induced cardiotoxicity in children. A literature review is presented of studies regarding the use of the biomarkers B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-pro-BNP), cardiac troponin T (cTnT), and cardiac troponin I (cTnI) in relation with anthracycline-induced cardiotoxicity in children. Six of 14 studies in children showed a significant relation between elevated biomarkers BNP, NT-pro-BNP, and cTnT and cardiac dysfunction. Six studies, although small, suggest that BNP, NT-pro-BNP, and cTnT might be useful markers in the early detection of anthracycline-induced cardiotoxicity.