Left atrial reservoir longitudinal strain and its incremental value to the left ventricular global longitudinal strain in predicting anthracycline-induced cardiotoxicity.

BACKGROUND: Left ventricular global longitudinal strain (LVGLS) has been recommended by current guidelines for diagnosing anthracycline-induced cardiotoxicity. However, little is known about the early changes in left atrial (LA) morphology and function in this population. Our study aimed to evaluate the potential usefulness of LA indices and their incremental value to LVGLS with three-dimensional echocardiography (3DE) in the early detection of subclinical cardiotoxicity in patients with lymphoma receiving anthracycline. METHODS: A total of 80 patients with diffuse large B-cell lymphoma who received six cycles of anthracycline-based treatment were enrolled. Echocardiography was performed at baseline (T0), after four cycles (T1), and after the completion of six cycles of chemotherapy (T2). Left ventricular ejection fraction (LVEF), LVGLS, LA volumes, LA emptying fraction (LAEF), LA active emptying fraction (LAAEF), and LA reservoir longitudinal strain (LASr) were quantified with 3DE. Left atrioventricular global longitudinal strain (LAVGLS) was calculated as the sum of peak LASr and the absolute value of peak LVGLS (LAVGLS = LASr+|LVGLS|). LV cardiotoxicity was defined as a new LVEF reduction by ≥10 percentage points to an LVEF of ≤50%. RESULTS: Fourteen (17.5%) patients developed LV cardiotoxicity at T2. LA volumes, LAEF, and LAAEF remained stable over time. Impairment of LASr (28.35 ± 5.03 vs. 25.04 ± 4.10, p < .001), LVGLS (-22.77 ± 2.45 vs. -20.44 ± 2.62, p < .001), and LAVGLS (51.12 ± 5.63 vs. 45.61 ± 5.22, p < .001) was observed by the end of the fourth cycle of chemotherapy (T1). Statistically significant declines in LVEF (61.30 ± 4.73 vs. 57.08 ± 5.83, p < .001) were only observed at T2. The relative decrease in LASr (ΔLASr), LVGLS (ΔLVGLS), and LAVGLS (ΔLAVGLS) from T0 to T1 were predictors of LV cardiotoxicity. A ΔLASr of >19.75% (sensitivity, 71.4%; specificity, 87.9%; area under the curve (AUC), .842; p < .001), a ΔLVGLS of >13.19% (sensitivity, 78.6%; specificity, 74.2%; AUC, .763; p < .001), and a ΔLAVGLS of >16.80% (sensitivity, 78.6%; specificity, 93.9%; AUC, .905; p < .001) predicted subsequent LV cardiotoxicity at T2, with the AUC of ΔLAVGLS significantly larger than that of ΔLVGLS (.905 vs. .763, p = .027). Compared to ΔLVGLS, ΔLAVGLS showed improved specificity (93.9% vs. 74.2%, p = .002) and maintained sensitivity in predicting LV cardiotoxicity. CONCLUSIONS: LASr could predict anthracycline-induced LV cardiotoxicity with excellent diagnostic performance. Incorporating LASr into LVGLS (LAVGLS) led to a significantly improved specificity and maintained sensitivity in predicting LV cardiotoxicity.

Assessment of Feasibility and Interscan Variability of Short-time Cardiac MRI for Cardiotoxicity Evaluation in Breast Cancer.

Purpose To investigate the feasibility and interscan variability of short-time cardiac MRI protocol after chemotherapy in individuals with breast cancer. Materials and Methods A total of 13 healthy female controls (mean age, 52.4 years ± 13.2 [SD]) and 85 female participants with breast cancer (mean age, 51.8 years ± 9.9) undergoing chemotherapy prospectively underwent routine breast MRI and short-time cardiac MRI using a 3-T scanner with peripheral pulse gating in the prone position. Interscan, intercoil, and interobserver reproducibility and variability of native T1 and extracellular volume (ECV), as well as ventricular functional parameters, were measured using the intraclass correlation coefficient (ICC), standard error of measurement (SEM), or coefficient of variation (CoV). Results Left ventricular functional parameters had excellent interscan reproducibility (ICC ≥ 0.80). Left ventricular ejection fraction showed low interscan variability in control and chemotherapy participants (SEM, 2.0 and 1.2; CoV, 3.1 and 1.9, respectively). Native T1 showed excellent interscan (ICC, 0.75) and intercoil (ICC, 0.81) reproducibility in the control group and good interscan reproducibility (ICC, 0.72 and 0.73, respectively) in the participants undergoing immediate and remote chemotherapy. Interscan reproducibility for ECV was excellent in the control group and in the remote chemotherapy group (ICC, 0.93 and 0.88, respectively) and fair in the immediate chemotherapy group (ICC, 0.52). In the regional analysis, interscan repeatability and variability of native T1 and ECV were superior in the anteroseptum or inferoseptum than in other segments in the immediate chemotherapy group. Native T1 and ECV had good to excellent interobserver agreement across all groups. Conclusion Short-time cardiac MRI showed excellent results for interscan, intercoil, and interobserver reproducibility and variability for ventricular functional or tissue characterization parameters, suggesting that this modality is feasible for routine surveillance of cardiotoxicity evaluation in individuals with breast cancer. Keywords: Cardiac MRI, Heart, Cardiomyopathy ClinicalTrials.gov registration no. NCT03301389 Supplemental material is available for this article. © RSNA, 2024.

Progression of Myocardial 18F-FDG Uptake in a Patient with Cardiotoxicity. / Evolução da Captação Miocárdica de 18F-FDG em Paciente com Diagnóstico de Cardiotoxicidade.

The objective of this case report was to present the progression of chemotherapy-induced cardiotoxicity in a patient with lymphoma, highlighting the importance of myocardial fluor-18-fluorodeoxyglucose (18F-FDG) uptake by positron emission tomography coupled with computed tomography (PET/CT). 43-year-old female patient with uterine lymphoma, who underwent hysterectomy followed by three chemotherapy regimens and radiotherapy. The patient had episodes of acute heart failure two years after chemotherapy. Echocardiogram revealed a reduction in left ventricular ejection fraction (LVEF). A retrospective analysis of 18F-FDG PET/CT showed an increase in myocardial uptake in all tests performed during oncologic treatment. Despite disease remission, the patient developed heart failure with reduced LVEF. During chemotherapy, there was a diffuse, significant increase in myocardial 18F-FDG uptake, which preceded the decrease in myocardial performance and seemed to reflect metabolic changes in cardiomyocytes, related to cardiotoxicity. Would an analysis of myocardial 18F-FDG uptake yield a different cardiac outcome in this patient? This question is relevant, considering that other patients may benefit from the use of PET as an early marker of cardiotoxicity. Imaging tests are essential in the follow-up of patients at risk of cardiotoxicity. Although echocardiography remains the main imaging test in the diagnosis of cardiotoxicity, 18F-FDG PET/CT may be a powerful tool for the early diagnosis of this condition.

O objetivo deste relato é mostrar a evolução da cardiotoxicidade (CTX) por quimioterápicos em paciente com linfoma por exames de imagens, destacando a importância da captação miocárdica de flúor-18 fluordeoxiglicose (18F-FDG) pela tomografia por emissão de pósitrons, acoplada à tomografia computadorizada (PET/CT). Feminino, 43 anos, com linfoma uterino, submetida a histerectomia, três esquemas de quimioterapia (QT), sucessivamente, e radioterapia. Apresentou episódios de insuficiência cardíaca aguda dois anos após QT. Ecocardiograma mostrou redução da fração de ejeção do ventrículo esquerdo (FEVE). Análise retrospectiva do 18F-FDG PET/CT observou elevação da captação miocárdica em todos os exames durante o seguimento oncológico. Apesar da remissão oncológica, a paciente desenvolveu IC com FEVE reduzida. Durante a QT, ocorreu aumento difuso e significativo da captação miocárdica de 18F-FDG, que precedeu a queda do desempenho cardíaco, e pareceu refletir alterações metabólicas nos cardiomiócitos relacionadas à CTX. A análise da captação miocárdica de 18F-FDG modificaria o desfecho cardiológico da paciente? Esse questionamento é relevante, visto que outros pacientes podem se beneficiar desse método como marcador precoce de CTX. Os exames de imagem são imprescindíveis no acompanhamento de pacientes com risco de CTX. O ecocardiograma permanece como principal auxílio diagnóstico, porém o 18F-FDG PET/CT pode estar surgindo como uma poderosa ferramenta para um diagnóstico mais precoce dessa condição clínica.

Echocardiography versus Cardiac MRI for Measurement of Left Ventricular Ejection Fraction in Individuals with Cancer and Suspected Cardiotoxicity.

Purpose To compare left ventricular ejection fraction (LVEF) measured with echocardiography and cardiac MRI in individuals with cancer and suspected cardiotoxicity and assess the potential effect on downstream clinical decision-making. Materials and Methods In this prospective, single-center observational cohort study, participants underwent same-day two-dimensional (2D) echocardiography and cardiac MRI between 2011 and 2021. Participants with suboptimal image quality were excluded. A subset of 74 participants also underwent three-dimensional (3D) echocardiography. The agreement of LVEF derived from each modality was assessed using Bland-Altman analysis and at relevant thresholds for cardiotoxicity. Results A total of 745 participants (mean age, 60 years ± 5 [SD]; 460 [61.7%] female participants) underwent same-day echocardiography and cardiac MRI. According to Bland-Altman analysis, the mean bias was -3.7% ± 7.6 (95% limits of agreement [LOA]: -18.5% to 11.1%) for 2D echocardiography versus cardiac MRI. In 74 participants who underwent cardiac MRI, 3D echocardiography, and 2D echocardiography, the mean LVEFs were 60.0% ± 10.4, 58.4% ± 9.4, and 57.2% ± 8.9, respectively (P < .001). At the 50% LVEF threshold for detection of cardiotoxicity, there was disagreement for 9.3% of participants with 2D echocardiography and cardiac MRI. Agreement was better with 3D echocardiography and cardiac MRI (mean bias, -1.6% ± 6.3 [95% LOA: -13.9% to 10.7%]) compared with 2D echocardiography and cardiac MRI (mean bias, -2.8% ± 6.3 [95% LOA: -15.2% to 9.6%]; P = .016). Conclusion Two-dimensional echocardiography had variations of ±15% for LVEF measurement compared with cardiac MRI in participants with cancer and led to misclassification of approximately 10% of participants for cardiotoxicity detection. Three-dimensional echocardiography had better agreement with cardiac MRI and should be used as first-line imaging. Keywords: Echocardiography, MR Functional Imaging, Cardiac Supplemental material is available for this article. © RSNA, 2024.

Left ventricular mechanical dyssynchrony after chemotherapy in breast cancer patients with normal rest gated SPECT-MPI.

OBJECTIVES: Early diagnosis of chemotherapy-induced cardiotoxicity plays an important role in preventing heart failure. The main aim of our study was to assess left ventricular (LV) dyssynchrony measured by phase analysis of gated single-photon emission computed tomography (SPECT) as an early sign of cardiotoxicity after breast cancer chemotherapy. METHODS: This cross-sectional study was conducted on patients with stage ≤ 3 breast cancer and no history of cardiovascular disease or diabetes. After mastectomy, the patients underwent rest gated SPECT myocardial perfusion imaging (MPI). Sixty patients with normal gated SPECT-MPI were selected and the imaging was performed after chemotherapy with doxorubicin, cyclophosphamide and paclitaxel. LV function and contractility parameters were extracted by QGS software and the results were compared with the t test method. The abnormality of at least one of the three phase analysis indices was considered as left ventricular dyssynchrony (LVD). RESULTS: The average LV end-systolic volume and ejection fraction (LVEF) before and after chemotherapy were (16.2 ± 8.0 ml and 21.6 ± 11.6 ml) and (73.4 ± 7.9% and 67.5 ± 9.2%) respectively, which showed a significant decrease (P < 0.05). In 2 patients (3.3%), the LVEF decreased to less than 50% after chemotherapy. The average parameters of left ventricular contractility before and after chemotherapy were, respectively, as follows: PHB (24.1 ± 7.5 and 33.8 ± 16.4), PSD (9.4 ± 6.1 and 5.7 ± 1.9) and entropy (28.9 ± 7.1 and 35.6 ± 9.7), which showed a significant increase (P < 0.05). LVD was observed in 14 patients (23.4%) after chemotherapy and prevalence of LVD was significantly higher in patients who had received a cumulative dose of doxorubicin of more than 400 mg/m2 (P = 0.005). There was no relationship between age and body mass index with the incidence of LVD after chemotherapy (P > 0.05). CONCLUSION: Using phase analysis of gated SPECT-MPI, chemotherapy-induced LVD was seen in a significant number of patients with breast cancer, especially with a high cumulative dose of doxorubicin. LVD might indicate chemotherapy-induced cardiotoxicity before LVEF becomes abnormal.

Study of stress-strain loops on cardiotoxicity related to immune checkpoint inhibitors.

OBJECTIVE: To evaluate the effect of immune checkpoint inhibitors (ICIs) on left ventricular myocardial work by pressure-strain loop (PSL). METHODS: Forty-three immunotherapy patients were enrolled in the case group, and another 43 healthy volunteers were enrolled in the control group. They were examined by echocardiography before immunotherapy (T0 phase), after three cycles of treatment (T3 phase) and after six cycles of treatment (T6 phase). Conventional echocardiographic parameters, left ventricular global longitudinal strain (GLS), and myocardial work indices, including global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE), were collected for analysis to compare the results of the different immunotherapy cycles. RESULTS: There were no statistically significant differences of baseline characteristics, conventional echocardiographic parameters, left ventricular strain, and myocardial work indices between T0 phase and control group (all p > .05). There were no statistically significant differences in LVEF between T0, T3, and T6 phase (all p > .05). GLS, GWI, GCW, and GWE were decreased and GWW was increased in T3 and T6 phase. There were no statistically significant difference between GLS in T3 and T0 phase (q = .9057, p > .05). The difference was statistically significant between GLS in T6 and T0 phase (q = 5.5651, p < .01). The difference was statistically significant between GLS in T3 and T6phase(q = 4.6594, p < .01). There were statistically significant difference in GWI, GCW, GWE, and GWW in the T3 and T6 phase compared with the T0 phase (p < .01). CONCLUSION: PSL can effectively evaluate the effect of ICIs on left ventricular myocardial work, to provide a new method for the early clinical detection of ICIs-related cardiotoxicity.

Assessment of early anthracycline-induced cardiotoxicity and liver injury with T2 and T2* mapping in rabbit models.

OBJECTIVES: To evaluate the early prevalence of anthracycline-induced cardiotoxicity (AIC) and anthracycline-induced liver injury (AILI) using T2 and T2* mapping and to explore their correlations. MATERIALS AND METHODS: The study included 17 cardiotoxic rabbits that received weekly injections of doxorubicin and magnetic resonance imaging (MRI) every 2 weeks for 10 weeks. Cardiac function and T2 and T2* values were measured on each period. Histopathological examinations for two to five rabbits were performed after each MRI scan. The earliest sensitive time and the threshold of MRI parameters for detecting AIC and AILI based on these MRI parameters were obtained. Moreover, the relationship between myocardial and liver damage was assessed. RESULTS: Early AIC could be detected by T2 mapping as early as the second week and focused on the 7th, 11th, and 12th segments of left ventricle. The cutoff value of 46.64 for the 7th segment had the best diagnostic value, with an area under the curve (of 0.767, sensitivity of 100%, and specificity of 52%. T2* mapping could detect the change in iron content for early AIC at the middle interventricular septum and AILI as early as the sixth week (p = 0.014, p = 0.027). The T2* values of the middle interventricular septum showed a significant positive association with the T2* values of the liver (r = 0.39, p = 0.002). CONCLUSION: T2 and T2* mapping showed value one-stop assessment of AIC and AILI and could obtain the earliest MRI diagnosis point and optimal parameter thresholds for these conditions. CLINICAL RELEVANCE STATEMENT: Anthracycline-induced cardiotoxicity could be detected by T2 mapping as earlier as the second week, mainly focusing on the 7th, 11th, and 12th segments of left ventricle. Combined with T2* mapping, hepatoxicity and supplementary cardiotoxicity were assessed by one-stop scan. KEY POINTS: • MRI screening time of cardiotoxicity was as early as the second week with focusing on T2 values of the 7th, 11th, and 12th segments of left ventricle. • T2* mapping could be used as a complement to T2 mapping to evaluate cardiotoxicity and as an effective index to detect iron change in the early stages of chemotherapy. • The T2* values of the middle interventricular septum showed a significant positive association with the T2* values of the liver, indicating that iron content in the liver and heart increased with an increase in the chemotherapeutic drugs.

Robustness of [18F]FDG PET/CT radiomic analysis in the setting of drug-induced cardiotoxicity.

BACKGROUND AND OBJECTIVES: Standardization of radiomic data acquisition protocols is still at a very early stage, revealing a strong need to work towards the definition of uniform image processing methodologies The aim of this study is to identify sources of variability in radiomic data derived from image discretization and resampling methodologies prior to image feature extraction. Furthermore, to identify robust potential image-based biomarkers for the early detection of cardiotoxicity. METHODS: Image post-acquisition processing, interpolation, and volume of interest (VOI) segmentation were performed. Four experiments were conducted to assess the reliability in terms of the intraclass correlation coefficient (ICC) of the radiomic features and the effects of the variation of voxel size and gray level discretization. Statistical analysis was performed separating the patients according to cardiotoxicity diagnosis. Differences of texture features were studied with Mann-Whitney U test. P-values <0.05 after multiple testing correction were considered statistically significant. Additionally, a non-supervised k-Means clustering algorithm was evaluated. RESULTS: The effect of the variation in the voxel size demonstrated a non-dependency relationship with the values of the radiomic features, regardless of the chosen discretization method. The median ICC values were 0.306 and 0.872 for absolute agreement and consistency, respectively, when varying the discretization bin number. The median ICC values were 0.678 and 0.878 for absolute agreement and consistency, respectively, when varying the discretization bin size. A total of 16 first order, 6 Gray Level Co-occurrence Matrix (GLCM), 4 Gray Level Dependence Matrix (GLDM) and 4 Gray Level Run Length Matrix (GLRLM) features demonstrated statistically significant differences between the diagnosis groups for interim scans (P<0.05) for the fixed bin size (FBS) discretization methodology. However, no statistically significant differences between diagnostic groups were found for the fixed bin number (FBN) discretization methodology. Two clusters based on the radiomic features were identified. CONCLUSIONS: Gray level discretization has a major impact on the repeatability of the radiomic features. The selection of the optimal processing methodology has led to the identification of texture-based patterns for the differentiation of early cardiac damage profiles.

RISK SCORE MODEL FOR PREDICTING CARDIOTOXICITY IN BREAST CANCER: DIAGNOSTIC VALUE OF HIGH-SENSITIVITY CARDIAC TROPONIN T. / ШКАЛА РИЗИКУ КАРДІОТОКСИЧНОСТІ У ХВОРИХ НА РАК ГРУДНОЇ ЗАЛОЗИ: ДІАГНОСТИЧНЕ ЗНАЧЕННЯ ВИСОКОЧУТЛИВОГО СЕРЦЕВОГО ТРОПОНІНУ Т.

Cardiovascular diseases are the second leading cause of death among breast cancer (BC) patients. Prediction of cardiovascular toxicity (CT) is an important part of the successful treatment and survival of patients. OBJECTIVE: to develop a risk score model for cardiovascular toxicity (CT) predicting, based on cardiovascular risk factors (RFs), RFs associated with cancer therapy, and troponin levels. MATERIAL AND METHODS: The study included 76 BC patients with a prospective analysis of their clinical and treatment data, RFs, echocardiographic indicators before the start of treatment and after 6 months, and an increase in troponin level. Among all RFs, the most significant RFs of CT were: radiation therapy, treatment with anthracyclines, and cardiovascular diseases. Based on the obtained results, a combined CT risk score was developed and proposed.According to the sum of points, patients were divided into groups: group 1 - with a low risk of CT development, the sum of points < 5; group 2 - moderate risk, 6-7 points; group 3 - high risk, > 8 points. RESULTS: In a pilot prospective study, an analysis of the RFs of CT was provided, compared to echocardiography data and the degree of troponin increase in dynamic observation; the risk score model for the CT prediction was developed for BC patients stratification. According to the developed score, BC patients with a total of > 8 points are considered to have a high risk of CT complications. CONCLUSIONS: The use of the proposed risk model score with calculation of the RFs of CT along with high-sensitivity troponin increase during cancer treatment allows predicting the risk of CT developing at the early stages - before the onset of clinical manifestations. Accordingly, these BC patients have a high risk of CT, and the use of personalized cardiac monitoring together with cardioprotective therapy can prevent cardiovascular complications.

Summary of Cardiac Computed Tomographic Imaging in Cardio-Oncology: An Expert Consensus Document of the Society of Cardiovascular Computed Tomography.

PURPOSE: The purpose of this document is to develop a summary of recommendations from the "Cardiac Computed Tomographic Imaging in Cardio-Oncology: An Expert Consensus Document of the Society of Cardiovascular Computed Tomography (SCCT)" document and provide commentary on key recommendations that are relevant to radiation oncology. METHODS: In July 2019, the SCCT convened a multidisciplinary panel of experts to develop a consensus document based on a literature search and a formal consensus process, which was separately published in 2022. A new panel consisting of the radiation oncologist from the original guideline and additional radiation oncologists was formed to address SCCT recommendations and their implications for radiation oncology. SUMMARY: The SCCT consensus document included 6 core sections. Two of these sections were identified as particularly relevant to radiation oncologists. These include evaluation of shared risk factors and role of cardiac computed tomography in risk stratification of patients with cancer (section 1) and the role of cardiac computed tomography in the evaluation of the effects of radiation therapy (section 4). These recommendations are summarized, with additional commentary on the role of radiation oncologists as individual practitioners and radiation oncology practices as a whole in evaluation of coronary artery calcifications on computed tomography images; assessment of the effects of radiation therapy on cardiovascular risk after treatment; and management of patients at elevated risk of cardiovascular sequelae of treatment. Radiation oncologists should be aware of the recommendations in the SCCT consensus document and consider those elements that relate to their practice. This summary document calls attention to the key roles and limitations of radiation oncologists and radiation oncology practices in managing cardiotoxicity risk and highlights the need for ongoing study on the effects of radiation therapy on the heart, cardiac substructures, and long-term risk of cardiotoxicity related to treatment.

Advances in Screening for Radiation-Associated Cardiotoxicity in Cancer Patients.

PURPOSE OF REVIEW: Radiation is foundational to the treatment of cancer and improves overall survival. Yet, it is important to recognize the potential cardiovascular effects of radiation therapy and how to best minimize or manage them. Screening-both through imaging and with biomarkers-can potentially identify cardiovascular effects early, allowing for prompt initiation of treatment to mitigate late effects. RECENT FINDINGS: Cardiac echocardiography, magnetic resonance imaging (MRI), computed tomography, and measurements of troponin and natriuretic peptides serve as the initial screening tests of choice for RICD. Novel imaging applications, including positron emission tomography and specific MRI parameters, and biomarker testing, including myeloperoxidase, growth differentiation factor 15, galectin 3, micro-RNA, and metabolomics, hold promise for earlier detection and more specific characterization of RICD. Advances in imaging and novel applications of biomarkers have potential to identify subclinical RICD and may reveal opportunities for early intervention. Further research is needed to elucidate optimal imaging screening modalities, biomarkers, and surveillance strategies.

3D-based strain analysis and cardiotoxicity detection in cancer patients received chemotherapy.

BACKGROUND: Chemotherapy-induced cardiotoxicity has become a prevalent complication. Regular monitoring of patients who received chemotherapy using 3D strain parameters may aid in early detection of myocardial damage and its prevention. The purpose of this study was to evaluate the effectiveness of three-dimensional speckle tracking imaging (3D-STI) in diagnosing and predicting the likelihood of cardiotoxicity. This was achieved by conducting a systematic review of original research articles. OBJECTIVES: To evaluate the role of 3D speckle tracking echocardiography in early detection of cardiotoxicity. METHODS: Relevant case control studies published prior to December 2022 were extracted to assess cardiotoxicity by 3D STE in patients after chemotherapy. RESULTS: A total of 1991 chemotherapy treated patients and control patients were included in the present review via pooling 22 studies. CONCLUSIONS: 3D speckle tracking echocardiography has the utility of non-invasive and objective evaluation of changes in left ventricular function in cancer patients undergoing chemotherapy. ROSPERO REGISTRATION NO: Study ID, CRD42023383790 on PROSPERO: International prospective register of systematic reviews.

Prognostic value of coronary atherosclerosis and CAC score for the risk of chemotherapy-related cardiac dysfunction (CTRCD): The protocol of ANTEC study.

BACKGROUND: Cardiological complications of oncological treatment, including the most serious one, heart failure, constitute a significant and still unsolved clinical problem. A history of dyslipidemia and complications of atherosclerosis, including coronary artery disease, are established risk factors for cardiotoxicity in cancer patients. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed. This protocol describes a study aiming to assess the prognostic value of coronary atherosclerosis burden and the CAC score on the onset of cardiac dysfunction associated with cancer therapy. METHODS: ANTEC (Atherosclerosis iN chemoTherapy-rElated Cardiotoxicity) is a single-site, prospective, observational study to evaluate the influence of the coronary atherosclerosis and CAC score assessed by computed tomography on the development of left ventricular systolic dysfunction in cancer patients with at least moderate cardiotoxicity risk. A group of 80 patients diagnosed with cancer prior to high-dose anthracycline chemotherapy (doxorubicin ≥ 240 mg / m2 body weight or epirubicin ≥ 600 mg / m2 body weight), without a history of heart failure and coronary artery disease, will be included in the study. Patient follow-up is planned for 12 months. In all patients, coronary computed tomographic angiography (CCTA) will be performed once at the beginning of the study. The primary endpoint is the onset of cancer therapy-related cardiovascular toxicity, defined as mild, moderate, severe and very severe according to ESC 2022 Cardio-oncology guidelines. During follow up, echocardiography with GLS assessment will be performed every three months. Additionally, new biomarkers of atherosclerosis (IL-6, MPO, TNF-alpha) will be measured every 6 months. The study registration identifier on clinicaltrials.gov is NCT05118178. CLINICAL TRIALS REGISTRY: This study is listed on cinicaltrials.gov with identifier NCT05118178.

Diagnostic Value of Three-Dimensional Speckle Tracking Imaging Strain Parameters for Detection of Cancer Chemotherapy-Related Cardiac Dysfunction: A Meta-Analysis. / Valor Diagnóstico de Parâmetros Tridimensionais de Strain de Imagem de Speckle Tracking para Detecção de Disfunção Cardíaca Relacionada à Quimioterapia do Câncer: Uma Metanálise.

BACKGROUND: Chemotherapeutic agents (e.g., anthracyclines, trastuzumab) commonly used for treating malignant tumors have been demonstrated to have cardiotoxic effects, which is associated with poor prognosis. Three-dimensional echocardiography has been used to predict cancer chemotherapy-induced cardiac dysfunction. OBJECTIVES: Evaluation of the diagnostic performance of strain parameters, global area strain (GAS), longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS) by meta-analysis. METHODS: Relevant studies were searched from the Embase, PubMed, and Web of Science databases. Statistical analysis was performed using Stata 12. The summary receiver operating characteristic curve, sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and corresponding 95% confidence interval for the four strain parameters were pooled. P<0.05 was considered statistically significant. RESULTS: Nine studies involving 650 participants were included. GAS and GLS showed significant diagnostic advantages over GCS and GRS. For GAS, the sensitivity was 0.85 (0.70, 0.93) and specificity was 0.82(0.78, 0.86) with PLR of 4.76 (3.55, 6.39) and NLR of 0.18 (0.09, 0.39) and an area under the curve (AUC) of 0.85 (0.82, 0.88). For GLS, the sensitivity was 0.81 (0.74, 0.86) and specificity was 0.81(0.68, 0.90) with PLR of 4.35(2.42, 7.80) and NLR of 0.23 (0.17, 0.33) and an AUC of 0.85 (0.82, 0.88). The GCS showed a sensitivity of 0.63 and a specificity of 0.79 with an AUC of 0.77. The GRS showed a sensitivity of 0.74 and a specificity of 0.66 with an AUC of 0.73. CONCLUSION: 3D-STI strain parameters GAS and GLS showed good performance in detecting early cardiac dysfunction in patients with tumors receiving chemotherapy.

FUNDAMENTO: Agentes quimioterápicos (por exemplo, antraciclinas, trastuzumabe) comumente usados para o tratamento de tumores malignos demonstraram ter efeitos cardiotóxicos, que estão associados a um prognóstico ruim. A ecocardiografia tridimensional tem sido usada para prever a disfunção cardíaca induzida pela quimioterapia do câncer. OBJETIVOS: Avaliação do desempenho diagnóstico de parâmetros de strain, área global de strain (AGS), strain longitudinal (SLG), strain circunferencial (SCG) e strain radial (SRG) por metanálise. MÉTODOS: Estudos relevantes foram pesquisados nas bases de dados Embase, PubMed e Web of Science. A análise estatística foi realizada usando Stata 12. O resumo da curva característica operacional do receptor, sensibilidade, especificidade, razão de verossimilhança positiva (RVP), razão de verossimilhança negativa (RVN), e o correspondente intervalo de confiança de 95% para os quatro parâmetros de strain foram combinados. P<0,05 foi considerado estatisticamente significativo. RESULTADOS: Nove estudos envolvendo 650 participantes foram incluídos. AGS e SLG mostraram vantagens diagnósticas significativas sobre SCG e SRG. Para AGS, a sensibilidade foi de 0,85 (0,70, 0,93) e a especificidade foi de 0,82 (0,78, 0,86) com RVP de 4,76 (3,55, 6,39) e RVN de 0,18 (0,09, 0,39) e uma área sob a curva (AUC) de 0,85 (0,82, 0,88). Para SLG, a sensibilidade foi de 0,81 (0,74, 0,86) e a especificidade foi de 0,81 (0,68, 0,90) com RVP de 4,35 (2,42, 7,80) e RVN de 0,23 (0,17, 0,33) e uma AUC de 0,85 (0,82, 0,88).OGCS mostrou uma sensibilidade de 0,63 e uma especificidade de 0,79 com uma AUC de 0,77.O SRG mostrou uma sensibilidade de 0,74e uma especificidade de 0,66 com umAUC de 0,73. CONCLUSÃO: Parâmetros 3D-STI de strain AGS e SLG mostraram bom desempenho na detecção precoce de disfunção cardíaca em pacientes com tumores recebendo quimioterapia.

Tales from the future-nuclear cardio-oncology, from prediction to diagnosis and monitoring.

Cancer and cardiovascular diseases (CVD) often share common risk factors, and patients with CVD who develop cancer are at high risk of experiencing major adverse cardiovascular events. Additionally, cancer treatment can induce short- and long-term adverse cardiovascular events. Given the improvement in oncological patients' prognosis, the burden in this vulnerable population is slowly shifting towards increased cardiovascular mortality. Consequently, the field of cardio-oncology is steadily expanding, prompting the need for new markers to stratify and monitor the cardiovascular risk in oncological patients before, during, and after the completion of treatment. Advanced non-invasive cardiac imaging has raised great interest in the early detection of CVD and cardiotoxicity in oncological patients. Nuclear medicine has long been a pivotal exam to robustly assess and monitor the cardiac function of patients undergoing potentially cardiotoxic chemotherapies. In addition, recent radiotracers have shown great interest in the early detection of cancer-treatment-related cardiotoxicity. In this review, we summarize the current and emerging nuclear cardiology tools that can help identify cardiotoxicity and assess the cardiovascular risk in patients undergoing cancer treatments and discuss the specific role of nuclear cardiology alongside other non-invasive imaging techniques.

Modelling cardiac mechanics in doxorubicin-induced cardiotoxicity following childhood acute lymphoblastic leukemia using a combination of cardiac magnetic resonance imaging, cardiopulmonary exercise testing and the CircAdapt model.

Children with acute lymphoblastic leukemia (ALL) are treated with doxorubicin-based chemotherapy that can lead to cardiotoxicity which is a well-known cause of mortality. This study aims to characterize myocardial subtle changes induced by doxorubicin-related cardiotoxicity. We used the combination of cardiac magnetic resonance (CMR) imaging, cardiopulmonary exercise testing and the CircAdapt model to explore hemodynamics and intraventricular mechanisms at rest and during exercise in 53 childhood ALL survivors. A sensitivity analysis of the CircAdapt model identified the most influencing parameters on the left ventricle volume. ANOVA were performed to explore significant differences between left ventricle stiffness, contractility, and arteriovenous pressure drop, as well as survivors' prognostic risk groups. No significant differences were observed between prognostic risk groups. The left ventricle stiffness and left ventricle contractility were non-significantly higher in survivors receiving cardioprotective agents (94.3 %), compared to those at standard and high prognostic risk (77 % and 86 %, respectively). In both left ventricle stiffness and left ventricle contractility, we observed that survivors receiving cardioprotective agents were close to the nominal value of CircAdapt (healthy reference group value is 100 %). This study allowed to improve our knowledge of potential subtle myocardial changes induced by doxorubicin-related cardiotoxicity in childhood ALL survivors. This study confirms that survivors exposed to a high cumulative dose of doxorubicin during treatments are at potential risk of myocardial changes many years after the end of their cancer, while cardio-protective agents may prevent changes in cardiac mechanical properties.

Longitudinal assessment of cardiac parameters through MRI in breast cancer patients treated with anti-HER2 therapy.

BACKGROUND: We evaluated the early changes in left ventricular (LV) volumetric, functional, and tissue characteristics in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with trastuzumab and/or pertuzumab at cardiac magnetic resonance imaging (MRI). METHODS: HER2-positive breast cancer patients undergoing planned anti-HER2 therapy and nonanthracycline-based chemotherapy were enrolled and subdivided into dual anti-HER2 (trastuzumab plus pertuzumab) group and trastuzumab group. Cardiac MRI was performed before treatment and three months after starting, covering ventricular volumes, cardiac function, systolic myocardial strain, myocardial oedema, and T1 and T2 relaxation times. Cardiac dysfunction was primarily defined as a > 10% reduction in LV ejection fraction (LVEF) to < 55% and/or a > 15% global longitudinal strain (GLS) change at the follow-up MRI examination. RESULTS: Twenty-four HER2-positive patients were evaluated (16 in the dual anti-HER2 group, 8 in the trastuzumab group). Six patients developed cardiac dysfunction at follow-up, five of them in the dual anti-HER2 group. One patient developed symptomatic heart failure, and five patients developed asymptomatic cardiac dysfunction. Patients displayed significantly decreased systolic function and increased T1 and T2 relaxation time at follow-up (p ≤ 0.031). Systolic dysfunction remained significant in the dual anti-HER2 group. The decrease in GLS in the trastuzumab group was not significant (p = 0.169). T1 and T2 relaxation times tended to increase, but this was not significant at subgroup analysis. CONCLUSIONS: Cardiac MRI scans showed frequent signs of subclinical cardiotoxicity after short-term anti-HER2 therapy and nonanthracycline-based chemotherapy; the effect was slightly stronger in patients treated with dual therapy. KEY POINTS: • A frequent subclinical cardiotoxicity was detected by cardiac magnetic resonance imaging after short-term anti-human epidermal growth factor receptor 2 (HER2) therapy. • The change in myocardial strain was more marked in patients treated with dual (trastuzumab plus pertuzumab) than with trastuzumab only anti-HER2 therapy. • Cardiotoxicity surveillance through MRI is an interesting option particularly in patients treated with dual anti-HER2 therapy.

Comprehensive Cardiovascular Magnetic Resonance Tissue Characterization and Cardiotoxicity in Women With Breast Cancer.

Importance: There is a growing interest in understanding whether cardiovascular magnetic resonance (CMR) myocardial tissue characterization helps identify risk of cancer therapy-related cardiac dysfunction (CTRCD). Objective: To describe changes in CMR tissue biomarkers during breast cancer therapy and their association with CTRCD. Design, Setting, and Participants: This was a prospective, multicenter, cohort study of women with ERBB2 (formerly HER2)-positive breast cancer (stages I-III) who were scheduled to receive anthracycline and trastuzumab therapy with/without adjuvant radiotherapy and surgery. From November 7, 2013, to January 16, 2019, participants were recruited from 3 University of Toronto-affiliated hospitals. Data were analyzed from July 2021 to June 2022. Exposures: Sequential therapy with anthracyclines, trastuzumab, and radiation. Main Outcomes and Measures: CMR, high-sensitivity cardiac troponin I (hs-cTnI), and B-type natriuretic peptide (BNP) measurements were performed before anthracycline treatment, after anthracycline and before trastuzumab treatment, and at 3-month intervals during trastuzumab therapy. CMR included left ventricular (LV) volumes, LV ejection fraction (EF), myocardial strain, early gadolinium enhancement imaging to assess hyperemia (inflammation marker), native/postcontrast T1 mapping (with extracellular volume fraction [ECV]) to assess edema and/or fibrosis, T2 mapping to assess edema, and late gadolinium enhancement (LGE) to assess replacement fibrosis. CTRCD was defined using the Cardiac Review and Evaluation Committee criteria. Fixed-effects models or generalized estimating equations were used in analyses. Results: Of 136 women (mean [SD] age, 51.1 [9.2] years) recruited from 2013 to 2019, 37 (27%) developed CTRCD. Compared with baseline, tissue biomarkers of myocardial hyperemia and edema peaked after anthracycline therapy or 3 months after trastuzumab initiation as demonstrated by an increase in mean (SD) relative myocardial enhancement (baseline, 46.3% [16.8%] to peak, 56.2% [18.6%]), native T1 (1012 [26] milliseconds to 1035 [28] milliseconds), T2 (51.4 [2.2] milliseconds to 52.6 [2.2] milliseconds), and ECV (25.2% [2.4%] to 26.8% [2.7%]), with P <.001 for the entire follow-up. The observed values were mostly within the normal range, and the changes were small and recovered during follow-up. No new replacement fibrosis developed. Increase in T1, T2, and/or ECV was associated with increased ventricular volumes and BNP but not hs-cTnI level. None of the CMR tissue biomarkers were associated with changes in LVEF or myocardial strain. Change in ECV was associated with concurrent and subsequent CTRCD, but there was significant overlap between patients with and without CTRCD. Conclusions and Relevance: In women with ERBB2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy, CMR tissue biomarkers suggest inflammation and edema peaking early during therapy and were associated with ventricular remodeling and BNP elevation. However, the increases in CMR biomarkers were transient, were not associated with LVEF or myocardial strain, and were not useful in identifying traditional CTRCD risk.

Serial Cardiac MRI for Quantification of the Dynamics of Anthracycline-Induced Subclinical Myocardial Injury.

BACKGROUND: Anthracyclines are known to be associated with chemotherapy-induced cardiotoxicity. Limited data focus on dynamic myocardial injury during the course of chemotherapy in patients with breast cancer. PURPOSE: To investigate the variation of tissue characterization and myocardial deformation derived by cardiac MRI during anthracycline chemotherapy. STUDY TYPE: Prospective. POPULATION: Fifty-eight female breast cancer patients (mean age: 52.82 ± 2.61 years) were enrolled. FIELD STRENGTH/SEQUENCE: A 3.0-T, cardiac MRI including cine balanced steady-state free precession, a modified Looker-Locker inversion recovery (MOLLI), and a fast spin echo (FSE) T2-weighted sequences were performed. ASSESSMENT: Cardiac MRI was performed baseline and after two, four, and six cycles of chemotherapy. Assessment of global longitudinal strain (GLS), global circumstance strain (GCS), global radial strain (GRS), and strain rate (GLS-s, GCS-s, GRS-s) and T1, T2 and T2* were accomplished by CVI42. The anthracycline dose and risk factors were also collected before each cardiac MRI. STATISTICAL TESTS: Analysis of variance (ANOVA) for repeated measures was used to compare the changes in LVEF cardiac function, strain and T1/T2/T2* parameters over time. Pearson correlation analyses were performed to estimate the potential associations between differences in myocardial characteristics (∆) and the chemotherapy cycle. A P value <0.05 was considered statistically significant. RESULTS: LVEF was not significantly different from pretreatment MRI regarding each cycle of chemotherapy (P = 0.54). Compared with baseline, patients had significantly lower GLS (-15.85% ± 0.83%, -14.50% ± 0.88%, -12.34% ± 1.01% vs. -18.82% ± 0.92%) and GLS-s (-0.71% ± 0.07%, -0.65% ± 0.05%, -0.64% ± 0.04% vs. -0.95 ± 0.06%) and increased T2 values (57.21 ± 4.27 msec, 58.60 ± 3.93 msec, 58.10 ± 3.17 msec vs. 43.88 ± 3.28 msec) at two, four and six cycles of chemotherapy treatment. ∆GLS and ∆GLS-s were significantly associated with the chemotherapy cycle (correlation coefficients for GLS = 0.75, GLS-s = 0.75). DATA CONCLUSION: Cardiac MRI can precisely detect the dynamic changes of anthracycline-induced subclinical myocardial injury that is represented as a gradually decrease in GLS and GLS-s. These parameters may provide new insight for monitoring risk and therapy in patients with breast cancer. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 1.