RESUMO
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.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/diagnóstico por imagem , Cardiotoxicidade/diagnóstico por imagem , Estudos de Viabilidade , Imageamento por Ressonância Magnética , Reprodutibilidade dos Testes , Volume Sistólico , Função Ventricular Esquerda , Adulto , IdosoRESUMO
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.
Assuntos
Antraciclinas , Antibióticos Antineoplásicos , Cardiotoxicidade , Doxorrubicina , Animais , Coelhos , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/tratamento farmacológico , Ferro , Fígado/diagnóstico por imagem , Doxorrubicina/uso terapêuticoRESUMO
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.
Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias da Mama , Cardiopatias , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/tratamento farmacológico , Cardiopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Trastuzumab/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
Cardiotoxicity may present as (pulmonary) hypertension, acute and chronic coronary syndromes, venous thromboembolism, cardiomyopathies/heart failure, arrhythmia, valvular heart disease, peripheral arterial disease, and myocarditis. Many of these disease entities can be diagnosed by established cardiovascular diagnostic pathways. Nuclear medicine, however, has proven promising in the diagnosis of cardiomyopathies/heart failure, and peri- and myocarditis as well as arterial inflammation. This article first outlines the spectrum of cardiotoxic cancer therapies and the potential side effects. This will be complemented by the definition of cardiotoxicity using non-nuclear cardiovascular imaging (echocardiography, CMR) and biomarkers. Available nuclear imaging techniques are then presented and specific suggestions are made for their application and potential role in the diagnosis of cardiotoxicity.
Assuntos
Antineoplásicos , Cardiomiopatias , Insuficiência Cardíaca , Miocardite , Neoplasias , Medicina Nuclear , Humanos , Antineoplásicos/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Cardiotoxicidade/tratamento farmacológico , Miocardite/induzido quimicamente , Miocardite/tratamento farmacológicoRESUMO
BACKGROUND: Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage. METHODOLOGY: This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage. DISCUSSION: The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.
Assuntos
Cardiotoxicidade/diagnóstico por imagem , Ecocardiografia/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias/radioterapia , Lesões por Radiação/diagnóstico , Neoplasias da Mama/radioterapia , Cardiotoxicidade/etiologia , Protocolos Clínicos , Células Endoteliais , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Contração Miocárdica/fisiologia , Peptídeo Natriurético Encefálico/análise , Fragmentos de Peptídeos/análise , Doses de Radiação , Volume Sistólico , Troponina T/análise , Disfunção Ventricular EsquerdaRESUMO
PURPOSE OF REVIEW: In this review, we summarize the major known cardiac toxicities of common chemotherapeutic agents and the role of nuclear cardiac imaging for the surveillance and assessment of cancer therapeutics-related cardiac dysfunction in routine clinical practice. RECENT FINDINGS: Cardiotoxicity from chemotherapy causes a significant mortality and limits potentially life-saving treatment in cancer patients. Close monitoring of cardiac function during chemotherapy is an accepted method for reducing these adverse effects especially in patients with cancer therapeutics-related cardiac dysfunction. Nuclear imaging is a sensitive, specific, and highly reproducible modality for assessment of cardiac function. Nuclear imaging techniques including equilibrium radio nucleotide angiography, myocardial perfusion imaging, and novel experimental molecular imaging are the various objective tools available in addition to conventional echocardiography and cardiac magnetic resonance imaging in the surveillance, assessment, and follow-up of cancer therapeutics-related cardiac dysfunction.
Assuntos
Antineoplásicos , Cardiopatias , Neoplasias , Antineoplásicos/efeitos adversos , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Ecocardiografia , Cardiopatias/induzido quimicamente , Cardiopatias/diagnóstico por imagem , Humanos , Neoplasias/tratamento farmacológicoRESUMO
With the increasing overall survival of cancer patients due to recent discoveries in oncology, the incidence of side effects is also rising, and along with secondary malignancies, cardiotoxicity is one of the most concerning side effects, affecting the quality of life of cancer survivors. There are two types of cardiotoxicity associated with chemotherapy; the first one is acute, life-threatening but, fortunately, in most of the cases, reversible; and the second one is with late onset and mostly irreversible. The most studied drugs associated with cardiotoxicity are anthracyclines, but many new agents have demonstrated unexpected cardiotoxic effect, including those currently used in multiple myeloma treatment (proteasome inhibitors and immunomodulatory agents), tyrosine kinase inhibitors used in the treatment of chronic myeloid leukemia and some forms of acute leukemia, and immune checkpoint inhibitors recently introduced in treatment of refractory lymphoma patients. To prevent irreversible myocardial damage, early recognition of cardiac toxicity is mandatory. Traditional methods like echocardiography and magnetic resonance imaging are capable of detecting structural and functional changings, but unable to detect early myocardial damage; therefore, more sensible biomarkers like troponins and natriuretic peptides have to be introduced into the current practice. Baseline assessment of patients allows the identification of those with high risk for cardiotoxicity, while monitoring during and after treatment is important for early detection of cardiotoxicity and prompt intervention.
Assuntos
Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Cardiotoxicidade/prevenção & controle , Neoplasias Hematológicas/tratamento farmacológico , Fatores Imunológicos/efeitos adversos , Antraciclinas/administração & dosagem , Antineoplásicos/administração & dosagem , Biomarcadores/sangue , Sobreviventes de Câncer , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Ecocardiografia , Neoplasias Hematológicas/diagnóstico por imagem , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Fatores Imunológicos/administração & dosagem , Imageamento por Ressonância Magnética , Peptídeos Natriuréticos/sangue , Peptídeos Natriuréticos/genética , Inibidores de Proteassoma/administração & dosagem , Inibidores de Proteassoma/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Qualidade de Vida/psicologia , Troponina/sangue , Troponina/genéticaRESUMO
Introduction: Drug-induced myocardial dysfunction is an important safety concern during drug development. Oncology compounds can cause myocardial dysfunction, leading to decreased left ventricular ejection fraction and heart failure via several mechanisms. Cardiovascular imaging has a major role in the early detection and monitoring of cardiotoxicity. Echocardiography is the method of choice because of its widespread availability, low cost, and absence of radiation exposure. Cardiac magnetic resonance imaging can provide better reliability, reproducibility, and accuracy in the detection of drug-induced myocardial dysfunction. In addition, it enables assessment of myocardial edema, fibrosis, and necrosis. Cardiac serologic biomarkers such as troponins and B-type natriuretic peptides are used in combination with imaging during drug development. This article provides a general overview of each imaging modality and practical guidance for early detection and monitoring of cardiotoxicity.Areas covered: Cardiovascular imaging modalities and cardiac biomarkers for monitoring of cardiac function and early detection of drug-induced myocardial dysfunction in drug development.Expert opinion: Some new drugs especially in the oncology field, can cause myocardial dysfunction. Depending on the strength of pre-clinical or clinical data, CV imaging modalities and cardiac biomarkers play an important role in the early detection and mitigation plans for such drugs during their development.
Assuntos
Antineoplásicos/efeitos adversos , Biomarcadores/sangue , Cardiotoxicidade/diagnóstico por imagem , Desenvolvimento de Medicamentos/métodos , Ecocardiografia/métodos , Imageamento por Ressonância Magnética/métodos , Animais , Cardiotoxicidade/sangue , Diagnóstico Precoce , HumanosRESUMO
Increasing nanomedicinal approaches have been developed to effectively inhibit tumor growth; however, critical questions such as whether a nanomedicinal approach can mitigate latent side effects are barely addressed. To this end, we established a zebrafish xenograft tumor model, combining pseudodynamic three-dimensional cardiac imaging and image analysis to enable simultaneous and quantitative determination of the change of tumor volume and cardiac function of zebrafish upon specific nanoformulation treatment. Doxorubicin (DOX), a well-known chemotherapeutic agent with cardiotoxicity, and a recently developed DOX-loaded nanocomposite were employed as two model drugs to demonstrate the effectiveness to utilize the proposed evaluation platform for rapid validation. The nanoformulation significantly mitigated DOX-associated cardiotoxicity, while retaining the efficacy of DOX in inhibiting tumor growth compared to administration of carrier-free DOX at the same dose. We anticipate that this platform possesses the potential as an efficient assessment system for nanoformulated cancer therapeutics with suspected toxicity and side effects to vital organs such as the heart.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Cardiotoxicidade/prevenção & controle , Doxorrubicina/uso terapêutico , Coração/efeitos dos fármacos , Nanocompostos/química , Animais , Técnicas de Imagem Cardíaca , Cardiotoxicidade/diagnóstico por imagem , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Ouro/química , Ouro/toxicidade , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Nanocompostos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/química , Dióxido de Silício/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-ZebraRESUMO
BACKGROUND: Anthracyclines, a widely used chemotherapy agent with a definite survival improvement, can result in cardiac toxicity presenting with HF (heart failure). OBJECTIVE: We aim to assess the predictive value of cardiac biomarkers assessment in combination with myocardial two-dimensional strain echocardiography for early detection of cardiac toxicity in patients who underwent Anthracycline-based chemotherapy. METHODS: Fifty-two consecutive adult patients scheduled to undergo the first course of Anthracycline-based chemotherapy were subjected to the study. All the patients underwent highly sensitive 2D echocardiographic evaluation before the treatment, 4 and 12 weeks after completion of first-course chemotherapy. Longitudinal and segmental strains were measured. Serum levels of High-sensitive cardiac troponin I (hscTn-I) and N-terminal-pro-BNP (NT-proBNP) were also assessed before the initiation and 3 weeks after completion of first-course chemotherapy. RESULTS: Fifteen patients (28.8%) revealed a decrease in LVEF (Left Ventricular Ejection Fraction) throughout the evaluations, while just 5 patients met the criteria of cardiac toxicity (9.6%). AUC for Global Longitudinal Strain (GLS) ROC curve at 4 weeks of follow-up was calculated to be 0.968. Inferoseptal Systolic Longitudinal Strain (SLS) had the highest AUC value (AUC: 0.934) among different wall SLS. LVESD (Left Ventricular End-Systolic Diameter) at first and second evaluation could predict the risk of cardiac toxicity among LVESD, LVEDD (Left Ventricular End Diastolic Diameter) and LVEDV (Left Ventricular End-Diastolic Volume). Among cardiac biomarkers, hscTnI had higher sensitivity, while NT-proBNP had higher specificity for cardiac toxicity. CONCLUSION: This study has shown that hs-cTnI with good sensitivity can predict cardiac toxicity in Anthracycline-based chemotherapy receiver. The use of strain with speckle echocardiography method has a prognostic value; however, both longitudinal and segmental strain should be assessed. Lateral and inferoseptal SLS (Segmental Longitudinal Strain) are specific markers of cardiac toxicity in the course of anthracycline-related cardiac toxicity.
Assuntos
Antraciclinas/efeitos adversos , Biomarcadores/sangue , Cardiotoxicidade/sangue , Cardiotoxicidade/diagnóstico por imagem , Ecocardiografia/métodos , Adolescente , Adulto , Idoso , Antraciclinas/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Prognóstico , Estudos Prospectivos , Adulto JovemAssuntos
Humanos , Cardiomiopatias/induzido quimicamente , Neoplasias/tratamento farmacológico , Antineoplásicos/efeitos adversos , Radioterapia/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Ecocardiografia , Seguimentos , Disfunção Ventricular/induzido quimicamente , Cardiotoxicidade/diagnóstico por imagem , Cardiomiopatias/etiologiaRESUMO
BACKGROUND: There is a lack of consensus to guide which breast cancer patients require left ventricular function assessment (LVEF) prior to anthracycline therapy; the cost-effectiveness of screening this patient population has not been previously evaluated. METHODS: We performed a retrospective analysis of the Yale Nuclear Cardiology Database, including 702 patients with baseline equilibrium radionuclide angiography (ERNA) scan prior to anthracycline and/or trastuzumab therapy. We sought to examine associations between abnormal baseline LVEF and potential cardiac risk factors. Additionally, we designed a Markov model to determine the incremental cost-effectiveness ratio (ICER) of ERNA screening for women aged 55 with stage I-III breast cancer from a payer perspective over a lifetime horizon. RESULTS: An abnormal LVEF was observed in 2% (n = 14) of patients. There were no significant associations on multivariate analysis performed on self-reported risk factors. Our analysis showed LVEF screening is cost-effective with ICER of $45,473 per QALY gained. For a willingness-to-pay threshold of $100,000/ QALY, LVEF screening had an 81.9% probability of being cost-effective. Under the same threshold, screening was cost-effective for non-anthracycline cardiotoxicity risk of RR ≤ 0.58, as compared to anthracycline regimens. CONCLUSIONS: Age, preexisting cardiac risk factors and coronary artery disease did not predict a baseline abnormal LVEF. While the prevalence of an abnormal baseline LVEF is low in patients with breast cancer, our results suggest that cardiac screening prior to anthracycline is cost-effective.
Assuntos
Antraciclinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/diagnóstico por imagem , Imagem do Acúmulo Cardíaco de Comporta/economia , Trastuzumab/uso terapêutico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto , Idoso , Antraciclinas/efeitos adversos , Neoplasias da Mama/patologia , Cardiotoxicidade/economia , Análise Custo-Benefício , Feminino , Humanos , Cadeias de Markov , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Autorrelato , Trastuzumab/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/economia , Função Ventricular EsquerdaRESUMO
BACKGROUND: Radiation therapy (RT)-induced cardiotoxicity is among the concerning sequelae of breast cancer (BCA) treatment, particularly in HER2-positive BCA patients who receive anthracyclines and trastuzumab-based therapy. The aim of this study was to assess for early RT-induced changes in echocardiographic and circulating biomarkers of left ventricular (LV) function and evaluate their association with radiation dose to the heart among patients with HER2-positive BCA treated with contemporary RT. METHODS: A total of 47 women with HER2-positive BCA who were treated with an anthracycline, trastuzumab, and RT to the breast and/or chest wall ± regional lymph nodes were included in this study. Two-dimensional echocardiography with speckle-tracking imaging was performed at baseline (prechemotherapy), prior to and after RT (pre-RT and post-RT), and 6 months post-RT. High-sensitivity troponin I (hsTnI) was measured pre-RT and post-RT. Associations between mean heart dose (MHD) and changes in LV function after RT were examined in multivariable linear regression models. RESULTS: The MHD was 1.8 ± 1.5 Gy for patients receiving left-sided RT (n = 26) and 1.1 ± 1.3 Gy for patients receiving right-sided RT (n = 21). Pre-RT, post-RT, and 6-month post-RT echocardiograms were performed at median (interquartile range) of 49 days (27, 77) before and 54 days (25, 78) and 195 days (175, 226) after RT, respectively. Compared with pre-RT, a minimal decrease in LV ejection fraction was observed post-RT (61% ± 7% vs 59% ± 8%; P = .003) without any significant change in global longitudinal, circumferential, or radial strain or diastolic indices at the post-RT timepoint. Median (interquartile range) concentrations of hsTnI decreased from 5.7 pg/mL (3.0, 8.7) pre-RT to 3.7 pg/mL (2.0, 5.9) post-RT. There was no significant change in systolic or diastolic indices of LV function at 6 months post-RT compared with pre-RT. MHD was not associated with changes in echocardiographic parameters of LV function after RT. CONCLUSIONS: Breast RT using contemporary techniques can be delivered without evidence of early subclinical LV dysfunction or injury as measured by echocardiography and hsTnI in patients treated with anthracyclines and trastuzumab. Future studies should focus on identifying alternative biomarkers to elucidate early RT-induced cardiovascular effects and further characterizing long-term cardiovascular outcomes associated with contemporary breast RT.
Assuntos
Neoplasias da Mama/radioterapia , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Ecocardiografia Doppler/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Adulto , Idoso , Antraciclinas/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Biomarcadores/sangue , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Estudos Retrospectivos , Trastuzumab/administração & dosagemRESUMO
OBJECTIVE: Survivors of childhood cancer treated with anthracyclines carry the risk for developing late-onset cardiotoxicity. The purpose of this study was to evaluate left ventricular (LV) function in this patient group and compare it with healthy controls by means of conventional and speckle tracking echocardiography (STE) after exposure to chemotherapy. MATERIAL AND METHODS: Conventional and STE were performed in 45 childhood cancer survivors (mean age 11 ± 4.6; 26 male) treated with anthracyclines (median cumulative dosage 240 mg/m2 ; range, 100-460) and compared with age, gender and body surface area matched healthy controls. Follow-up period after chemotherapy was 21.9 ± 17.8 months. Blood samples were taken from survivors and controls to determine brain natriuretic peptide (BNP). RESULTS: Following anthracycline exposure, pediatric cancer survivors had lower longitudinal, radial anteroseptal, and radial anterior strain values compared to controls (P < .05). The calculated global longitudinal and global radial strain values were lower compared to the control group (P < .05). Both groups had normal ejection fraction (EF) and fractional shortening (FS). Brain natriuretic peptide (BNP) levels of both groups were in the normal range. CONCLUSION: Despite normal EF and FS, children exposed to anthracycline therapy may have late-onset subtle changes of LV strain values measured by STE. Whether these changes of strain can predict future risk of developing heart failure needs to be explored in further studies.
Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Sobreviventes de Câncer , Ecocardiografia/métodos , Neoplasias/tratamento farmacológico , Disfunção Ventricular Esquerda/induzido quimicamente , Adolescente , Adulto , Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Criança , Pré-Escolar , Daunorrubicina/efeitos adversos , Daunorrubicina/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Estudos Prospectivos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto JovemRESUMO
The use of echocardiography for the assessment of patients undergoing potentially cardiotoxic cancer treatments and for follow-up of treated patients is increasing and has become a significant public health problem due to the need for repeated examinations over time. Despite the technological advances of echocardiography, there are still uncertainties about how best to use this technique to identify and guide the management of cardiotoxicity. The purpose of this article is to discuss the role of echocardiography in the study of ventricular dysfunction due to cancer treatments, with the aim to clarify the main echocardiographic information to be provided, the methods to apply and the strategies to implement to streamline as much as possible the use of echocardiography in the field of cardioncology.
Assuntos
Ecocardiografia , Neoplasias/complicações , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem , Antineoplásicos/efeitos adversos , Cardiotoxicidade/complicações , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Humanos , Neoplasias/tratamento farmacológicoRESUMO
AIMS: We sought to assess whether global longitudinal strain (GLS) measured early during treatment with anthracyclines (at a cumulative dose of 150 mg/m2) can predict subsequent alterations in left ventricular ejection fraction. METHODS AND RESULTS: Eighty-six patients with Hodgkin's disease, non-Hodgkin's lymphoma, or acute leukaemia and receiving anthracyclines were prospectively included. Patients underwent complete echocardiography on four occasions: baseline (V1); after reaching a cumulative dose of 150 mg/m2 (V2); end of treatment (V3); and 1 year follow-up (V4). Six patients developed cardiotoxicity, defined as a decrease in left ventricular ejection fraction of >10 percentage points, to a value <53%, at V4. GLS measured at V1 and V2 was significantly lower in the cardiotoxicity group vs. the controls (P = 0.042 and P = 0.01, respectively). Compared with GLS at V1, GLS obtained at V2 provided incremental predictive information and appeared to be the strongest predictor of cardiotoxicity (area under the receiver-operating-characteristic curve, 0.82). At a threshold of -17.45% for GLS measured at V2, the sensitivity and specificity of detecting cardiotoxicity were 67% (95% confidence interval 33-100) and 97% (95% confidence interval 94-100), respectively. CONCLUSION: GLS greater than -17.45%, obtained after 150 mg/m2 of anthracycline therapy, is an independent predictor of future anthracycline-induced cardiotoxicity. These findings should encourage physicians to perform echocardiography earlier during treatment with anthracyclines.
Assuntos
Antraciclinas/efeitos adversos , Cardiotoxicidade/diagnóstico por imagem , Neoplasias Hematológicas/tratamento farmacológico , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto , Idoso , Antraciclinas/uso terapêutico , Cardiotoxicidade/etiologia , Cardiotoxicidade/fisiopatologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Ecocardiografia , Feminino , Neoplasias Hematológicas/patologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Variações Dependentes do Observador , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Volume Sistólico/efeitos dos fármacosRESUMO
PURPOSE: The goal of this study was to evaluate late cardiotoxic effects of anthracyclines (ATC) by evaluating cardiac sympathetic activity in a cohort of asymptomatic patients previously treated with ATC for childhood cancers. METHODS: We studied 89 asymptomatic patients previously treated with ATC with a normal echocardiogram (49 men and 40 women) and a control group of 40 healthy individuals (26 men and 14 women). Both groups underwent planar myocardial 123I-meta-iodobenzylguanidine scintigraphy (123I-mIBG). From these images, the early and late heart-to-mediastinum (H/M) ratio and washout rate (WR) were assessed. RESULTS: The mean survival at the time of the 123I-mIBG scintigraphy was 5.3 ± 3.4 years. Patients treated with ATC had a lower but clinical normal left ventricular ejection fraction (LVEF) compared to controls (60.44 ± 6.5 vs 64.1 ± 6.0%, P < 0.01). Both the late H/M ratio and WR were not able to discriminate ATC treated patients from controls. The cumulative ATC dose was the only independent predictor of the LVEF, explaining approximately 12% of the variation in LVEF (P = 0.01). CONCLUSIONS: Although the pathophysiology behind ATC cardiotoxicity is most likely multifactorial, myocardial sympathetic activity is not associated with a reduction in LVEF 5-years after completion of chemotherapy.
Assuntos
Antraciclinas/uso terapêutico , Doenças do Sistema Nervoso Autônomo/diagnóstico por imagem , Doenças do Sistema Nervoso Autônomo/mortalidade , Neoplasias/tratamento farmacológico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/mortalidade , 3-Iodobenzilguanidina , Adolescente , Adulto , Antineoplásicos/efeitos adversos , Brasil/epidemiologia , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/mortalidade , Causalidade , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Masculino , Neoplasias/mortalidade , Prevalência , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Patients with cancer can present with difficult management issues, as the medicine can sometimes cause sequelae destructive to healthy tissue. As this population lives longer, cardiotoxic effects are beginning to emerge, but the early recognition of this signal can prove difficult, with too late a recognition leading to lifelong cardiac impairment and dysfunction. Cardio-oncology can bridge this difficulty, and echocardiography and its newer imaging abilities are proving efficacious in this population. This article will address common sequelae of cardiotoxic treatment regimens and offer recommendations for echocardiographic surveillance. We recommend echocardiography, preferably three-dimensional and strain imaging, to monitor for cardiotoxic myocardial effects before, during, and after chemotherapy with cardiotoxic drug regimens, particularly anthracycline derivatives. A reduction in left ventricular (LV) global longitudinal strain in all patients, or reduction in LV global circumferential strain or global radial strain in patients at intermediate to high risk for cardiotoxicity, despite normal LV ejection fraction warrants a clinical assessment on the benefits of continuing cardiotoxic chemotherapeutic agents. Lifelong surveillance using echocardiography for cardiotoxicity and radiation-related valvular, pericardial, and coronary artery disease is prudent.