Perfil de liberación de biomarcadores miocárdicos en pacientes con enfermedades hemato-oncológicas que reciben trasplante de progenitores hematopoyéticos / Profile or myocardial biomarkers release in patients with hemato-oncological diseases who receive hematopoietic stem cell transplantation / Perfil de liberação de biomarcadores miocárdicos em pacientes com doenças hemato-oncológicas que recebem transplante de células-tronco hematopoéticas

Introducción: las enfermedades cardiovasculares (CV) son la primera causa de muerte en quienes sobreviven al cáncer. Aunque el trasplante de progenitores hematopoyéticos (TPH) se asocia con grados variables de cardiotoxicidad, estas complicaciones han sido escasamente caracterizadas. Objetivo: analizar el perfil de liberación de biomarcadores miocárdicos como potenciales indicadores subclínicos de cardiotoxicidad en pacientes sometidos a TPH. Material y método: estudio descriptivo, analítico, prospectivo transversal y unicéntrico, reclutando pacientes derivados a la policlínica de cardio-oncología, con indicación de TPH en octubre de 2018-marzo de 2020. Se realizaron controles clínicos, ECG, bioquímicos (troponina I TnI y péptido natriurético del tipo BBNP) e imagenológicos según algoritmo de seguimiento. Las variables discretas se presentan como n (%) y las continuas mediante media ± DE o mediana RIQ. Los valores evolutivos de biomarcadores séricos se compararon mediante test de Friedman. La fracciónde eyección del VI (FEVI) basal se comparó con la de los 3 meses del TPH mediante test de Wilcoxon. Resultados: se incluyeron 19 pacientes, 37% mujeres, de 43,8 ± 15,7 años. No se detectaron modificaciones significativas de la FEVI en los controles evolutivos. En ningún caso se observó aumento de la TnI. Los valores de BNP aumentaron en 6 pacientes (32%), con diferencias significativas al mes postrasplante (basal: 13,6 1;6,1-30,9 vs. primer mes: 38,9 16,3-120,0 pg/ml, p = 0,036); con una mayor elevación en aquellos pacientes que recibieron antimetabolitos vs. otros fármacos (basal: 13,6 1;6,1-30,9 vs. al primer mes: 67,0 ;21,3-174,9 pg/ml, p = 0,039). El aumento de BNP no se asoció con el riesgo CV. Conclusión: la liberación de BNP posterior al TPH es un fenómeno frecuente (32% de los pacientes), alcanza un máximo al mes, independientemente de la FEVI. El subgrupo de pacientes que recibió antimetabolitos presentó una mayor liberación precoz de BNP.

Introduction: cardiovascular (CV) diseases are the leading cause of death in those who survive cancer. Although hematopoietic stem cell transplantation (HSCT) is associated with diverse grades of cardiotoxicity, these complications have been poorly characterized. Objective: to analyze the release profile of myocardial biomarkers as a potential subclinical marker of cardiotoxicity in patients undergoing HSCT. Material and method: descriptive, analytical, prospective, cross-sectional, single-center study, recruiting patients referred to the cardio-oncology polyclinic, with indication for HSCT in October 2018-March 2020. Clinical, ECG, biochemical and imaging controls were performed according to the algorithm of follow-up. The evolutionary values of serum biomarkers were compared using the Friedman test. Baseline LVEF was compared with that of 3 months after HSCT using the Wilcoxon test. Results: 19 patients were included, 37% women, aged 43.8 ± 15.7 years. No changes in LVEF were detected. In no case was an increase in TnI observed. BNP values increased in 6 patients (32%), with significant differences one month after transplantation (baseline: 13.6 ;6.1-30.9 vs. first month: 38.9 ;16.3-120.0, p = 0.036), detecting a greater elevation in those patients who received antimetabolites vs. other rugs (baseline: 13.6 ;6.1-30.9 vs. at the first month: 67.0 21.3-174.0, p = 0.039). The increase in BNP was not associated with CV risk. Conclusion: BNP release after HSCT is frequent (32% of our patients), reaching a maximum at one month, regardless of LVEF. The subgroup of patients who received antimetabolites had a greater early release of BNP.

Introdução: as doenças cardiovasculares (CV) são a principal causa de morte em pessoas que sobrevivem ao câncer. Embora o transplante de células-tronco hematopoéticas (TCTH) esteja associado à diverso grado de cardiotoxicidade, essas complicações têm sido mal caracterizadas. Objetivo: analisar o perfil de liberação de biomarcadores miocárdicos como potenciais marcadores subclínicos de cardiotoxicidade em pacientes submetidos ao TCTH. Material e método: estudo descritivo, analítico, prospectivo, transversal, unicéntrico, com recrutamento de pacientes encaminhados à policlínica de cardio-oncologia, com indicação de TCTH de outubro de 2018 a março de 2020. Foram realizados controles clínicos, eletrocardiográficos, bioquímicos e de imagem de acordo com o algoritmo de acompanhamento. Os valores evolutivos dos biomarcadores séricos foram comparados pelo teste de Friedman. A FEVE basal foi comparada com a de 3 meses após o TCTH usando o teste de Wilcoxon. Resultados: foram incluídos 19 pacientes, 37% mulheres, com idade de 43,8 ± 15,7 anos. Nenhuma mudança na LVEF foi detectada. Em nenhum caso foi observado um aumento de TnI. Os valores de BNP aumentaram um mês após o transplante (linha de base: 13,6 6,1-30,9; vs. primeiro mês: 38,9 16,3-120,0, p = 0,036), se detectou uma maior elevação nos pacientes que receberam antimetabólitos vs. outros medicamentos (linha de base: 13,6 ;6,1-30,9; vs. no primeiro mês: 67,0 ;21,3-174,0;, p = 0,039). O aumento do BNP não foi associado ao risco CV. Conclusão: a liberação do BNP após o TCTH é frequente (32% de nossos pacientes), podendo chegar a no máximo um mês, independente da FEVE. O subgrupo de pacientes que recebeu antimetabólitos apresentou maior liberação precoce de BNP.

Trabalho Miocárdio: uma revisão sistemática do novo método de ecocardiografia e aplicações clínicas / Myocardial Work: a systematic review of novel echocardiography method and clinical applications

Fundamento: O trabalho miocárdico (MW) é uma nova modalidade de imagem que surgiu como uma forma potencial de avaliação da função ventricular esquerda (VE) em vários cenários clínicos. Ele calcula curvas de tensão de ecocardiografia de rastreamento de manchas (STE) com uma curva de pressão LV estimada utilizando curvas padrão de pressão arterial braquial de forma não invasiva. Objetivo: O objetivo desta pesquisa foi fornecer um resumo do conhecimento atual da MW não invasiva e suas aplicações clínicas, incluindo insuficiência cardíaca (IC), doença arterial coronariana (DAC), cardiomiopatia (CMP) e hipertensão (HTN). Além disso, são discutidas as limitações e recomendações da MW na prática clínica. Métodos: Pesquisamos no banco de dados online PubMed para nossa coleta de dados. Usamos as seguintes palavras-chave; (trabalho construtivo do miocárdio) OU (trabalho septal desperdiçado)) OU (trabalho miocárdico global)) OU (trabalho miocárdico)) OU (trabalho construtivo do miocárdio) OU (ecocardiografia nova). Revisamos ainda doze estudos com leitura de texto completo e incluídos nesta revisão sistemática. Resultados: Embora os índices de MW, particularmente GWI e GCW, tenham mostrado uma boa correlação com FE e parâmetros de deformação, a oportunidade de oferecer informações incrementais que não são afetadas pelas condições de carga tornou a aplicação de MW particularmente útil em uma variedade de configurações clínicas. Conclusão: Comparado ao FE e GLS, o MW é um teste promissor com maior sensibilidade e acurácia na identificação de indivíduos com doença cardiovascular. Os médicos também devem depender dos sintomas e dos achados do ECG até que uma extensa pesquisa multicêntrica validando essa estratégia seja feita para estabelecer o valor incremental da MW na avaliação ecocardiográfica diária. (AU)

Background: Myocardial work (MW) is a novel imaging modality that has emerged as a potential left ventricular (LV) function assessment in various clinical settings. MW calculates speckle-tracking echocardiography strain curves with an estimated LV pressure curve by non-invasively utilizing standard brachial blood pressure curves. Objective: This study aimed to provide a summary of current knowledge of non-invasive MW and its clinical applications, including in heart failure, coronary artery disease, cardiomyopathy, and hypertension. In addition, the limitations, and recommendations of MW in clinical practice are discussed. Methods: We searched the PubMed database using the following keywords: (myocardial constructive work) OR (wasted septal work) OR (global myocardial work) OR (myocardial work) OR (myocardial constructive work) OR (novel echocardiography). We further subjected 12 studies to full-text review and included them in this systematic review. Results: While MW indices, particularly global work index and global constructed work, have shown good correlations with ejection fraction (EF) and strain parameters, the opportunity of offering incremental information that is unaffected by loading conditions has made MW application particularly useful in a variety of clinical settings. Conclusion: Compared to EF and global longitudinal strain, MW is a promising test with higher sensitivity and accuracy for identifying individuals with cardiovascular disease. Clinicians should also evaluate symptoms and electrocardiographic findings until extensive multicenter studies validating this strategy are performed to establish the incremental value of MW in daily echocardiographic assessments.(AU)

Early Cardiac Effects of Contemporary Radiation Therapy in Patients With Breast Cancer.

PURPOSE: To characterize the early changes in echocardiographically derived measures of cardiac function with contemporary radiation therapy (RT) in breast cancer and to determine the associations with radiation dose-volume metrics, including mean heart dose (MHD). METHODS AND MATERIALS: In a prospective longitudinal cohort study of 86 patients with breast cancer treated with photon or proton thoracic RT, clinical and echocardiographic data were assessed at 3 time points: within 4 weeks before RT initiation (T0), within 3 days before 6 weeks after the end of RT (T1), and 5 to 9 months after RT completion (T2). Associations between MHD and echocardiographically derived measures of cardiac function were assessed using generalized estimating equations to define the acute (T0 to T1) and subacute (T0 to T2) changes in cardiac function. RESULTS: The median estimates of MHD were 139 cGy (interquartile range, 99-249 cGy). In evaluating the acute changes in left ventricular ejection fraction (LVEF) from T0 to T1, and accounting for the time from RT, age, race, preexisting cardiovascular disease, and an interaction term with anthracycline or trastuzumab exposure and MHD, there was a modest decrease in LVEF of borderline significance (0.22%; 95% confidence interval [CI], -0.44% to 0.01%; P = .06) per 30-day interval for every 100 cGy increase of MHD. Similarly, there was a modest worsening in longitudinal strain (0.19%; 95% CI, -0.01% to 0.39%; P = .06) per 30-day interval for each 100 cGy increase in MHD. We did not find significant associations between MHD and changes in circumferential strain or diastolic function. CONCLUSIONS: With modern radiation planning techniques, there are modest subclinical changes in measures of cardiac function in the short-term. Longer-term follow-up studies are needed to determine whether these early changes are associated with the development of overt cardiac disease.

Effect at One Year of Adjuvant Trastuzumab for HER2+ Breast Cancer Combined with Radiation or an Anthracycline on Left Ventricular Ejection Fraction.

To determine the impact of radiation therapy (XRT) in addition to trastuzumab (TZB) adjuvant chemotherapy for HER2+ breast cancer on left ventricular systolic function, we assessed demographics, oncologic treatment history including XRT exposure, and serial measurements of left ventricular ejection fraction (LVEF) in 135 consecutively identified women receiving TZB for treatment of adjuvant breast cancer. Longitudinal mixed effects models were fit to identify baseline to treatment changes in LVEF among those receiving TZB with or without concomitant anthracycline or XRT. Women averaged 53 ± 3 years in age, 77% were white, 62% patients had 1 or more cardiovascular risk factors at baseline, and mean duration of TZB was 11 ± 5 months. Seventy-seven women were treated with XRT and received between 4000 and 5500 cGy of radiation. The LVEF declined by an average of 3.4% after 1 year for those in the study. Relative to baseline upon completion of adjuvant TZB, LVEF remained reduced for those receiving anthracycline with or without XRT (p=0.002 for both), or XRT alone (p=0.002), but not in those without these therapies. Amongst patients treated only with XRT and TZB, LVEF declined 3.1% on average in those with left-sided disease and 6.9% on average in those with right-sided disease (p= 0.06, p= 0.008 respectively). Among women receiving TZB for adjuvant treatment of HER-2 positive breast cancer, the administration of XRT, anthracycline, or the combination of the 2 is associated with a persistent post-treatment as opposed to a temporary treatment related decline in LVEF.

New Cardiac Abnormalities After Radiotherapy in Breast Cancer Patients Treated With Trastuzumab.

PURPOSE: To evaluate cardiac imaging abnormalities after modern radiotherapy and trastuzumab in breast cancer patients. PATIENTS AND METHODS: All patients treated with trastuzumab and radiotherapy for breast cancer between 2006 and 2014 with available cardiac imaging (echocardiogram or multigated acquisition scan) were retrospectively analyzed. Cardiac abnormalities included myocardial abnormalities (atrial or ventricular dilation, hypertrophy, hypokinesis, and impaired relaxation), decreased ejection fraction > 10%, and valvular abnormalities (thickening or stenosis of the valve leaflets). Breast laterality (left vs. right) and heart radiation dose volume parameters were analyzed for association with cardiac imaging abnormalities. RESULTS: A total of 110 patients with 57 left- and 53 right-sided breast cancers were evaluated. Overall, 37 patients (33.6%) developed a new cardiac abnormality. Left-sided radiotherapy was associated with an increase in new cardiac abnormalities (relative risk [RR] = 2.51; 95% confidence interval [CI], 1.34-4.67; P = .002). Both myocardial and valvular abnormalities were associated with left-sided radiotherapy (myocardial: RR = 2.21; 95% CI, 1.06-4.60; P = .029; valvular: RR = 3.30; 95% CI, 0.98-10.9; P = .044). There was no significant difference in decreased ejection fraction between left- and right-sided radiotherapy (9.6% vs. 2.1%; P = .207). A mean heart dose > 2 Gy as well as volume of the heart receiving 20 Gy (V20), V30, and V40 correlated with cardiac abnormalities (mean heart dose > 2 Gy: RR = 2.00; P = .040). CONCLUSION: New cardiac abnormalities, including myocardial and valvular dysfunction, are common after trastuzumab and radiotherapy. The incidence of new abnormalities correlates with tumor laterality and cardiac radiation dose exposure. Long-term follow-up is needed to understand the clinical significance of these early imaging abnormalities.

ST2 levels increased and were associated with changes in left ventricular systolic function during a three-year follow-up after adjuvant radiotherapy for breast cancer.

OBJECTIVES: To search for biomarkers of RT-induced cardiotoxicity, we studied the behavior of ST2 during RT and three years after RT, and the associations with echocardiographic changes. MATERIALS AND METHODS: We measured soluble ST2 (ng/ml) in serum samples from 63 patients receiving RT for early breast cancer. Sampling and echocardiography were performed at baseline, after RT and at the three-year follow-up. Patients were grouped by >15% (group 1) and ≤15% (group 2) relative worsening in global longitudinal strain (GLS). RESULTS: ST2 levels tended to increase during RT, from a median (interquartile range; IQR) of 17.9 (12.4-22.4) at baseline to 18.2 (14.1-23.5) after RT (p = 0.075). By the three-year follow up, ST2 levels increased to 18.7 (15.8-24.2), p = 0.018. The increase in ST2 level was associated with worsening cardiac systolic function at three-year follow-up, GLS (rho = 0.272, p = 0.034) and left ventricular ejection fraction (LVEF) (rho = â”€0.343, p = 0.006). Group 1 (n = 14) had a significant increase in ST2 levels from 17.8 (12.3-22.5) at baseline to 18.4 (15.6-22.6) after RT, p = 0.035 and to 19.9 (16.0-25.1) three years after RT, p = 0.005. ST2 levels were stable in group 2 (n = 47): 17.8 (12.3-22.0) at baseline, 17.7 (12.6-23.5) after RT and 18.0 (15.5-22.4) at three years. CONCLUSION: ST2 may be useful for determining which patients are at risk for long-term cardiovascular toxicity following adjuvant breast cancer RT, but prospective clinical studies are needed to confirm this hypothesis.

Adjuvant radiotherapy-induced cardiac changes among patients with early breast cancer: a three-year follow-up study.

Background: In this study, we evaluate the evolution of cardiac changes during a three-year follow-up after adjuvant breast radiotherapy (RT). Methods: Sixty patients with left-sided and 20 patients with right-sided early stage breast cancer without chemotherapy were included in this prospective study. Echocardiography and cardiac biomarkers were evaluated before, immediately after and 3 years after RT. Radiation doses to cardiac structures were calculated. Results: In echocardiography, left ventricle (LV) systolic measurements had impaired at 3 years compared to baseline: the mean global longitudinal strain (GLS) worsened from -18 ± 3 to -17 ± 3 (p = .015), LV ejection fraction from 62 ± 5% to 60 ± 4% (p = .003) and the stroke volume from 73 ± 16 mL to 69 ± 15 mL (p = .015). LV diastolic function was also negatively affected: the isovolumetric relaxation time was prolonged (p = .006) and the first peak of diastole decreased (p = .022). Likewise, left atrial (LA) measurements impaired. These changes in echocardiography were more prominent in left-sided than in right-sided patients. The concurrent aromatase inhibitor (AI) use was associated with GLS impairment. In all patients, the N-terminal pro-brain natriuretic peptide (proBNP) values were median (interquartile range) 74 (41-125) ng/L at baseline, 75 (41-125) ng/L at the end of RT and 96 (56-162) ng/L at 3 years (p < .001 from baseline to 3 years). However, proBNP did not increase in right-sided patients. Conclusion: During the 3-year follow-up after RT, negative subclinical changes in cardiac biomarkers and in LV systolic and diastolic function were observed. The measured changes were more pronounced in left-sided patients. In addition, AI use was associated with impaired cardiac systolic function.

Cardiac Function After Radiation Therapy for Breast Cancer.

PURPOSE: The main purpose of this study was to test the hypothesis that incidental cardiac irradiation is associated with changes in cardiac function in breast cancer (BC) survivors treated with radiation therapy (RT). METHODS AND MATERIALS: We conducted a cross-sectional study consisting of 109 BC survivors treated with RT between 2005 and 2011. The endpoint was cardiac function, assessed by echocardiography. Systolic function was assessed with the left ventricular ejection fraction (LVEF) (n = 107) and the global longitudinal strain (GLS) of the left ventricle (LV) (n = 52). LV diastolic dysfunction (n = 109) was defined by e' at the lateral and septal region, which represents the relaxation velocity of the myocardium. The individual calculated RT dose parameters of the LV and coronary arteries were collected from 3-dimensional computed tomography-based planning data. Univariable and multivariable analysis using forward selection was performed to identify the best predictors of cardiac function. Robustness of selection was assessed using bootstrapping. The resulting multivariable linear regression model was presented for the endpoints of systolic and diastolic function. RESULTS: The median time between BC diagnosis and echocardiography was 7 years. No relation between RT dose parameters and LVEF was found. In the multivariable analysis for the endpoint GLS of the LV, the maximum dose to the left main coronary artery was most often selected across bootstrap samples. For decreased diastolic function, the most often selected model across bootstrap samples included age at time of BC diagnosis and hypertension at baseline. Cardiac dose-volume histogram parameters were less frequently selected for this endpoint. CONCLUSIONS: This study shows an association between individual cardiac dose distributions and GLS of the LV after RT for BC. No relation between RT dose parameters and LVEF was found. Diastolic function was most associated with age and hypertension at time of BC diagnosis. Further research is needed to make definitive conclusions.

Ultrasound stroke volume variation induced by passive leg raising and fluid responsiveness: An observational cohort study / Variación ultrasónica del volumen sistólico inducida por la elevación pasiva de la pierna y la respuesta de fluidos: estudio de cohortes observacional

Objective: To assess the performance of the ultrasound measurement of stroke volume (SV) coupled to passive leg raising (PLR) in predicting fluid responsiveness (FR). Design: A prospective cohort study was carried out in patients requiring volume expansion (VE). A transthoracic Doppler echocardiography (TTE) device was used for the measurement of SV. Four measurements were obtained: before and 90s after PLR, and before and after VE. The patients were subsequently classified according to their hemodynamic response to VE. Responders were defined by an increase in SV of at least 15% in response to VE. Results: Thirty maneuvers were studied. An increase in SV>15% in response to PLR was recorded in 21 cases. Hemodynamic indices taken in the first stage showed significant differences in the distensibility index of the inferior vena cava (dIVC), in the velocity-time integral of aortic blood flow (VTIAo) and in SV, with respective p-values of 0.009, 0.012 and 0.025. The SV changes induced by VE were significantly correlated to the SV changes induced by PLR, with a Spearman coefficient of 0.77 and a linear equation y=0.82 x+1.68. Fluid responsiveness can be efficiently predicted by assessing the effects of PLR on SV monitored by Doppler TTE, with a sensitivity of 94.7% and a negative predictive value of 88%. Conclusion: Our data support the interest of Doppler TTE as an effective tool in predicting FR through the assessment of SV in response to PLR, in hemodynamically unstable patients

Objetivo: Evaluar el rendimiento de la medida del volumen sistólico (VS) por ultrasonido junto con la elevación pasiva de piernas (EPP) para predecir la respuesta de fluidos (RF). Diseño: Estudio prospectivo de cohorte realizado en pacientes que requieren expansión de volumen (EV). Se utilizó un dispositivo doppler ecocardiográfico transtorácico (ETT) para la medición del VS. Se obtuvieron 4 mediciones: antes y 90s después de la EPP, y antes y después de la EV. Posteriormente, los pacientes se clasificaron según su respuesta hemodinámica a VE. Los respondedores se definieron por un aumento del VS de al menos 15% en respuesta a EV. Resultados: Se estudiaron 30 maniobras. Un aumento del VS>15% en respuesta a la EPP se informó en 21 casos. Los índices hemodinámicos tomados en la primera etapa mostraron diferencias significativas en el índice de distensibilidad de la vena cava inferior (dVCI), en la integral velocidad-tiempo del flujo sanguíneo aórtico (IVTAo) y en el VS con valores p respectivos en 0,009, 0,012 y 0,025. Los cambios del VS inducidos por EV se correlacionaron significativamente con los cambios del VS inducidos por EPP con un coeficiente de Spearman en 0,77 y una ecuación lineal en y=0,82× +1,68. La respuesta de fluidos se puede predecir eficazmente mediante la evaluación de los efectos de EPP en el VS vigilado por ETT-doppler con sensibilidad en el 94,7% y VPN en el 88%. Conclusión: Nuestros datos respaldan el interés del ETT-doppler como una herramienta eficaz en la predicción de la RF por la evaluación del VS en respuesta a la EPP en pacientes hemodinámicamente inestables

Early Changes in Cardiovascular Biomarkers with Contemporary Thoracic Radiation Therapy for Breast Cancer, Lung Cancer, and Lymphoma.

PURPOSE: We characterized the early changes in cardiovascular biomarkers with contemporary thoracic radiation therapy (RT) and evaluated their associations with radiation dose-volume metrics including mean heart dose (MHD), V5, and V30. METHODS AND MATERIALS: In a prospective longitudinal study of 87 patients with breast cancer, lung cancer, or mediastinal lymphoma treated with photon or proton thoracic RT, blood samples were obtained pre-RT and after completion of RT (median, 20 days; interquartile range [IQR], 1-35). High-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, placental growth factor (PIGF), and growth differentiation factor 15 (GDF-15) were measured. Associations between MHD, V5 and V30, and biomarker levels and associations between echocardiography-derived measures of cardiac function and biomarker levels were assessed in multivariable linear regression models. Analyses were performed according to the following subgroups: (1) breast cancer alone and (2) lung cancer and lymphoma combined. RESULTS: The median (IQR) estimates of MHD ranged from 1.3 Gy (0.9-2.4) in breast cancer (n = 60) to 6.8 Gy (5.4-10.2) in mediastinal lymphoma (n = 14) and 8.4 Gy (6.7-16.1) in lung cancer (n = 13) patients (P < .001). There were no significant increases in biomarker levels from pre-RT to post-RT in breast cancer. In lung cancer/lymphoma, PIGF increased from a median (IQR) of 20 ng/L (16-26) to 22 ng/L (16-30) (P = .005), and GDF-15 increased from 1171 ng/L (755-2493) to 1887 ng/L (903-3763) (P = .006). MHD, V5, and V30 were significantly associated with post-RT PIGF and GDF-15 levels in multivariable models. Changes in biomarkers were not significantly associated with changes in echocardiography-derived measures of cardiac function. CONCLUSION: Contemporary thoracic RT induces acute abnormalities in vascular and inflammatory biomarkers that are associated with radiation dose-volume metrics, particularly in lung cancer and mediastinal lymphoma. Long-term follow-up studies are needed to determine the impact of these changes on the development of overt cardiac disease.

Application of Circular Patch Plasty (Dor Procedure) or Linear Repair Techniques in the Treatment of Left Ventricular Aneurysms.

OBJECTIVE: The aim of this study was to evaluate early clinical outcomes and echocardiographic measurements of the left ventricle in patients who underwent left ventricular aneurysm repair using two different techniques associated to myocardial revascularization. METHODS: Eighty-nine patients (74 males, 15 females; mean age 58±8.4 years; range: 41 to 80 years) underwent post-infarction left ventricular aneurysm repair and myocardial revascularization performed between 1996 and 2016. Ventricular reconstruction was performed using endoventricular circular patch plasty (Dor procedure) (n=48; group A) or linear repair technique (n=41; group B). RESULTS: Multi-vessel disease in 55 (61.7%) and isolated left anterior descending (LAD) disease in 34 (38.2%) patients were identified. Five (5.6%) patients underwent aneurysmectomy alone, while the remaining 84 (94.3%) patients had aneurysmectomy with bypass. The mean number of grafts per patient was 2.1±1.2 with the Dor procedure and 2.9±1.3 with the linear repair technique. In-hospital mortality occurred in 4.1% and 7.3% in group A and group B, respectively (P>0.05). CONCLUSION: The results of our study demonstrate that post-infarction left ventricular aneurysm repair can be performed with both techniques with acceptable surgical risk and with satisfactory hemodynamic improvement.

Application of circular patch plasty (dor procedure) or linear repair techniques in the treatment of left ventricular aneurysms

Abstract Objective: The aim of this study was to evaluate early clinical outcomes and echocardiographic measurements of the left ventricle in patients who underwent left ventricular aneurysm repair using two different techniques associated to myocardial revascularization. Methods: Eighty-nine patients (74 males, 15 females; mean age 58±8.4 years; range: 41 to 80 years) underwent post-infarction left ventricular aneurysm repair and myocardial revascularization performed between 1996 and 2016. Ventricular reconstruction was performed using endoventricular circular patch plasty (Dor procedure) (n=48; group A) or linear repair technique (n=41; group B). Results: Multi-vessel disease in 55 (61.7%) and isolated left anterior descending (LAD) disease in 34 (38.2%) patients were identified. Five (5.6%) patients underwent aneurysmectomy alone, while the remaining 84 (94.3%) patients had aneurysmectomy with bypass. The mean number of grafts per patient was 2.1±1.2 with the Dor procedure and 2.9±1.3 with the linear repair technique. In-hospital mortality occurred in 4.1% and 7.3% in group A and group B, respectively (P>0.05). Conclusion: The results of our study demonstrate that post-infarction left ventricular aneurysm repair can be performed with both techniques with acceptable surgical risk and with satisfactory hemodynamic improvement.

Effect of Breast Irradiation on Cardiac Disease in Women Enrolled in BCIRG-001 at 10-Year Follow-Up.

PURPOSE: To investigate cardiac toxicity associated with breast radiation therapy (RT) at 10-year follow-up in BCIRG-001, a phase 3 trial comparing adjuvant anthracycline chemotherapy (fluorouracil, doxorubicin, and cyclophosphamide) with anthracycline-taxane chemotherapy (docetaxel, doxorubicin, and cyclophosphamide) in women with lymph node-positive early breast cancer. METHODS AND MATERIALS: Prospective data from all 746 patients in the control arm (fluorouracil, doxorubicin, and cyclophosphamide) of BCIRG-001 at 10-year follow-up were obtained from Project Data Sphere. Cardiac toxicities examined included myocardial infarction (MI), heart failure (HF), arrhythmias, and relative and absolute left ventricular ejection fraction decrease of >20% from baseline. Toxicities were compared between patients who received RT versus no RT, left-sided RT versus no RT, and internal mammary nodal RT versus no RT. RESULTS: Of the 746 patients, 559 (75%) received RT to a median dose of 50 Gy. Myocardial infarction occurred in 3 RT patients (0.5%) versus 6 no-RT patients (3%) (P=.01). Heart failure was seen in 15 RT patients (2.7%) versus 3 no-RT patients (1.6%) (P=.6). Among these, 35 RT patients (18%) had a left ventricular ejection fraction relative decrease of >20% baseline versus 7 (10%) who did not receive RT (P=.1). Arrhythmias were more common in RT patients (3.2%) versus no-RT patients (0%) (P=.01). On univariable and multivariable analysis HF was not significantly associated with RT, and MI was negatively associated with RT. CONCLUSIONS: In this retrospective analysis of prospective toxicity outcomes, there is an increased risk of arrhythmias but no clear evidence of significantly increased risk of MI or HF at 10 years in lymph node-positive women treated with breast RT and uniform adjuvant doxorubicin-based chemotherapy. Given the low incidence of these outcomes, studies with larger numbers are needed to confirm our findings.

Atorvastatin can ameliorate left atrial stunning induced by radiofrequency ablation for atrial fibrillation.

The objective of this study was to study the functional changes of the left atrium after radiofrequency ablation treatment for atrial fibrillation and the therapeutic effect of atorvastatin. Fifty-eight patients undergoing radiofrequency ablation for atrial fibrillation were randomly divided into non-atorvastatin group and atorvastatin group. Patients in the atorvastatin group were treated with atorvastatin 20 mg p.o. per night in addition to the conventional treatment of atrial fibrillation; patients in the non-atorvastatin group received conventional treatment of atrial fibrillation only. Echocardiography was performed before radiofrequency ablation operation and 1 week, 2 weeks, 3 weeks, and 4 weeks after operation. Two-dimensional ultrasound speckle tracking imaging system was used to measure the structural indexes of the left atrium. Results indicated that there was no significant change for indexes representing the structural status of the left atrium within a month after radiofrequency ablation (P > 0.05); however, there were significant changes for indexes representing the functional status of the left atrium. There were also significant changes in indexes reflecting left atrial strain status: the S and SRs of atorvastatin group were higher than those of non-atorvastatin group (P < 0.05). In summary, atorvastatin could improve left atrial function and shorten the duration of atrial stunning after radiofrequency ablation of atrial fibrillation.

Radiotherapy-induced global and regional differences in early-stage left-sided versus right-sided breast cancer patients: speckle tracking echocardiography study.

Radiotherapy (RT) to the thoracic region increases late cardiovascular morbidity and mortality. The impact of breast cancer laterality on cardiac function is largely unknown. The aim of this prospective study was to compare RT-induced changes in left-sided and right-sided breast cancer patients using speckle tracking echocardiography (STE). Sixty eligible patients with left-sided breast cancer and 20 with right-sided breast cancer without chemotherapy were evaluated prospectively before and early after RT. A comprehensive echocardiographic examination included three dimensional measurements and STE of the left ventricle (LV). The global longitudinal strain (GLS) was reduced from -18.3 ± 3.1 to -17.2 ± 3.3% (p = 0.003) after RT in patients with left-sided breast cancer. Similarly, regional analysis showed a reduction in the apical strain from -18.7 ± 5.3 to -16.7 ± 4.9% (p = 0.002) and an increase in basal values from -21.6 ± 5.0 to -23.3 ± 4.9% (p = 0.024). Patients with right-sided breast cancer showed deterioration in basal anterior strain segments from -26.3 ± 7.6 to -18.8 ± 8.9% (p < 0.001) and in pulsed tissue Doppler by 0.825 [0.365, 1.710] cm/s (p < 0.001). In multivariable analysis, the use of aromatase inhibitor (ß = -2.002, p = 0.001) and decreased LV diastolic volume (ß = -0.070, p = 0.025) were independently associated with the decrease in GLS. RT caused no changes in conventional LV systolic measurements. RT induced regional changes corresponded to the RT fields. Patients with left-sided breast cancer experienced apical impact and global decline, whereas patients with right-sided breast cancer showed basal changes. The regional differences in cardiac impact warrant different methods in screening and in the follow-up of patients with left-sided versus right-sided breast cancer.

Assessment of concomitant versus sequential trastuzumab on radiation-induced cardiovascular toxicity.

There are limited data regarding effect of trastuzumab on radiation-induced cardiovascular toxicity when used sequentially or concomitantly. This experimental study aims to investigate effect of trastuzumab on radiation-induced cardiovascular toxicity with respect to the treatment sequence. One hundred and eight female Wistar albino rats were divided into six groups (G): G1 was control, G2 was trastuzumab, and G3 was radiotherapy (RT); G4 and G6 were sequential RT and trastuzumab; and G5 was concomitant RT and trastuzumab groups, respectively. Rats were killed at 6th h, 21st and 70th days after RT; thoracic aorta and heart samples were obtained. Transthoracic echocardiography and functional studies evaluating relaxation of thoracic aorta were performed. Subendothelial edema scores of thoracic aorta samples at 21st and 70th days were higher in RT groups (G3, G4, G5, and G6) ( p < 0.001). There was a deterioration of relaxation responses of thoracic aorta samples in RT groups ( p < 0.001). Cardiac fibrosis (CF) scores revealed detrimental effect of RT beginning from 6th h and trastuzumab from 21st day. RT groups showed further deterioration of CF at 70th day. Ejection fraction, left ventricular mass, and fractional shortening were significantly decreased in G4, G5, and G6. Trastuzumab may increase pathological damage in cardiovascular structures when used with RT regardless of timing.

Long-term Risk of Heart Failure and Myocardial Dysfunction After Thoracic Radiotherapy: A Systematic Review.

BACKGROUND: Chest irradiation is a commonly used treatment for malignancy, with demonstrated symptomatic and survival benefit. The frequency and presentation of cardiovascular complications of radiotherapy remains unclear. METHODS: We performed a systematic review to evaluate the prevalence and manifestations of myocardial dysfunction (asymptomatic and symptomatic) in long-term cancer survivors treated with radiotherapy. RESULTS: Thoracic radiotherapy is associated with increased risk of heart failure in long-term follow-up, with hazard ratios ranging from 2.7 to 7.4 for Hodgkin lymphoma, and 1.5-2.4 for breast cancer. Although ejection fraction is often normal, systolic dysfunction has been more widely reported with modern techniques including 2-dimensional speckle strain and cardiac magnetic resonance. This might have implications for the selection of patients for cardioprotection. Despite common emphasis, diastolic functional abnormalities were infrequent in the long term. A limited amount of data suggest that right ventricular dysfunction is important in this population. CONCLUSIONS: The reports were heterogeneous, used different treatments, end points, and definitions of myocardial dysfunction, and most studies on the cardiac consequences of radiotherapy involved small numbers of patients and were published decades ago, making it difficult to formulate definitive conclusions for the current era.

Brain natriuretic peptide as a cardiac marker of transient radiotherapy-related damage in left-sided breast cancer patients: A prospective study.

PURPOSE: Our study evaluated brain natriuretic peptide (BNP) changes over time after adjuvant radiotherapy (RT) in women with left-sided breast cancer investigating its correlation with heart dosimetric parameters. METHODS: Forty-three patients underwent clinical cardiac examination, electrocardiogram (ECG), echocardiography and BNP measurement before RT (T0) and 1 (T1), 6 (T6) and 12 months (T12) after. After T12 cardiac assessment was performed annually in each patient. Mean values and standard deviation (SD) of BNP, left ventricular ejection fraction (LVEF), V20, V25, V30, V45 and mean dose were calculated. Normalized BNP (BNPn) was calculated as follows: BNPnT1 = BNPT1/BNPT0, BNPnT6 = BNPT6/BNPT0, BNPnT12 = BNPT12/BNPT0. Absolute BNP and BNPn values were used for data analysis. RESULTS: Median follow-up from the end of RT to the last check-up was 87 months (range 37-120 months). Minimum follow-up was 74 months except for two patients, who died at respectively 37 and 47 months after RT. In all patients LVEF did not change significantly (p = 0.22) after RT. BNP increased significantly (p < 0.001), particularly 1 and 6 months after RT. It slightly decreased after 12 months. BNP did not correlate with V20, V25, V30, V45, mean dose and MHD. All BNPn correlated significantly (p < 0.05) with V20, V25, V30, V45, mean dose and MHD. Four patients had a cardiac event; in the only subject who developed myocardial infarction, V20, V25, V30 and V45 were the highest and BNP increased from T1 and persisted high even at T12. CONCLUSION: Our results confirm that BNP could be a useful minimally invasive marker of early RT related cardiac impairment.

Cardiac Function After Multimodal Breast Cancer Therapy Assessed With Functional Magnetic Resonance Imaging and Echocardiography Imaging.

PURPOSE: Breast intensity modulated radiation therapy (IMRT) reduces high-dose heart volumes but increases low-dose volumes. We prospectively assessed heart changes after 3D conformal RT (3DCRT) and IMRT for left-sided breast cancer. Heart dose was analyzed individually, 3DCRT patients were moderately exposed, and IMRT was performed only in patients with unacceptably high heart doses upon 3DCRT planning. METHODS AND MATERIALS: In 49 patients (38 patients received 3DCRT; 11 patients received IMRT; and 20 patients received neoadjuvant or adjuvant chemotherapy) magnetic resonance imaging (MRI) and echocardiography were performed before and at 6, 12, and 24 months after treatment. RESULTS: Mean heart dose for IMRT was 12.9 ± 3.9 Gy versus 4.5 ± 2.4 Gy for 3DCRT. Heart volumes receiving >40 Gy were 2.6% (3DCRT) versus 1.3% (IMRT); doses were >50 Gy only with 3DCRT. Temporary ejection fraction (EF) decrease was observed on MRI after 6 months (63%-59%, P=.005) resolving at 24 months. Only 3 patients had pronounced largely transient changes of EF and left ventricular enddiastolic diameter (LVEDD). Mitral (M) and tricuspid (T) annular plane systolic excursion (MAPSE and TAPSE) were reduced over the whole cohort (still within normal range). After 24 months left ventricular remodeling index decreased in patients receiving chemotherapy (0.80 vs 0.70, P=.028). Neither wall motion abnormalities nor late enhancements were found. On echocardiography, in addition to EF findings that were similar to those on MRI, global strain was unchanged over the whole cohort at 24 months after a transient decrease at 6 and 12 months. Longitudinal strain decreased in the whole cohort after 24 months in some segments, whereas it increased in others. CONCLUSIONS: Until 24 months after risk-adapted modern multimodal adjuvant therapy, only subclinical cardiac changes were observed in both 3DCRT patients with inclusion of small to moderate amounts of heart volume in RT tangents and in the patients treated with IMRT and reduced high-dose heart exposure.

¿Deberían mantenerse los betabloqueantes como terapia de primera línea en el tratamiento de pacientes con fibrilación auricular e insuficiencia cardiaca? / Should beta blockers remain as first-line therapy in the treatment of patients with atrial fibrillation and heart failure?

Introducción: Aunque todas las guías de práctica clínica recomiendan el empleo de los betabloqueantes en los pacientes con insuficiencia cardiaca sintomática y fracción de eyección reducida (ICFER), el beneficio de este tratamiento en los pacientes en lo que coexiste la fibrilación auricular (FA) es menos claro. Métodos: Se realizó un metaanálisis de datos individuales de pacientes con ICFER provenientes de 10 ensayos clínicos en los que se comparaba la eficacia y la seguridad de los betabloqueantes frente al placebo, y en los que se analizaba la mortalidad. De los 18.254 pacientes incluidos, 13.946 (76%) estaban en ritmo sinusal en el electrocardiograma basal, y 3.066 (17%) se encontraban en FA. La variable primaria del estudio fue la mortalidad por cualquier causa. El análisis se realizó por intención de tratar. Resultados: Tras un seguimiento medio de 1,5 años, las tasas crudas de mortalidad fueron del 16% en los pacientes en ritmo sinusal y del 21% en los pacientes en FA. Mientras que en los pacientes en ritmo sinusal el tratamiento con betabloqueantes se asoció con una reducción significativa de la mortalidad por cualquier causa del 27% (HR: 0,73; IC 95%: 0,67-0,80; p < 0,001), los betabloqueantes no tuvieron ningún efecto significativo en los pacientes en FA (HR: 0,97; IC 95%: 0,83-1,14; p = 0,73; valor de p interacción 0,002). Resultados similares se encontraron con respecto a la mortalidad cardiovascular y a la hospitalización por IC. Esta falta de eficacia de los betabloqueantes sobre la mortalidad total en los pacientes con FA fue independiente de la edad, el sexo, la fracción de eyección, la clase funcional, la frecuencia cardiaca y el tratamiento basal. Aproximadamente el 15% de los pacientes en ambos grupos discontinuaron el tratamiento con betabloqueantes (1-2% debido a efectos adversos específicos como la hipotensión o la bradicardia). Conclusiones: Los betabloqueantes no deberían emplearse de manera preferencial sobre otros fármacos utilizados para el control de la frecuencia cardiaca en pacientes con ICFER y FA, ni con el fin de mejorar el pronóstico en esta población (AU)

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