Valor del strain longitudinal global en la detección precoz de cardiotoxicidad inducida por quimioterapia / Global longitudinal strain value in the early detection of chemotherapy-induced cardiotoxicity

RESUMEN Introducción: Los avances en la detección precoz y el tratamiento del cáncer han reducido de manera significativa la mortalidad. El resultado neto es el surgimiento de una cohorte de pacientes cuya supervivencia es suficiente para evidenciar los efectos secundarios de las terapias utilizadas. La cardiotoxicidad es el conjunto de enfermedades cardiovasculares derivadas de los tratamientos onco-hematológicos. Objetivos: Evaluar el papel de la deformación miocárdica (strain) longitudinal global en la detección precoz de cardiotoxicidad en pacientes con tratamiento quimioterápico. Método: Se realizó un estudio cuantitativo, analítico, longitudinal, prospectivo en 44 pacientes con diagnóstico de cáncer de mama o linfoma, que iniciaron tratamiento con quimioterapia en el Instituto de Oncología y Radiobiología de Cuba, en el período comprendido entre febrero de 2017 y abril de 2018. Se utilizaron métodos primarios y secundarios para la recolección del dato primario y se emplearon varias pruebas estadísticas para su análisis. Resultados: Las medias de edad y tiempo de tratamiento fueron de 47,7 años y 5,05 meses, respectivamente. Predominó la hipertensión arterial (18,1%) como factor de riesgo y la mayor cardiotoxicidad (27,8%) en pacientes con disfunción diastólica previa. Entre los que desarrollaron cardiotoxicidad, la variable que demostró mayor afectación fue el strain longitudinal global (p<0,0001), con una reducción de 19,6% respecto al basal. Conclusiones: El strain longitudinal global es un índice ecocardiográfico de deformación miocárdica, que presentó un valor discriminante significativo con respecto a la cardiotoxicidad en pacientes que recibieron tratamiento quimioterápico.

ABSTRACT Introduction: Advances in early detection and treatment of cancer have significantly reduced mortality. The net result is the emergence of a cohort of patients whose survival is sufficient to evidence the side effects of the used therapies. Cardiotoxicity is the set of cardiovascular diseases resulting from onco-hematological treatments. Objectives: To evaluate the role of global longitudinal strain in the early detection of cardiotoxicity in patients undergoing chemotherapy. Method: A quantitative, analytical, prospective, longitudinal study was carried out in 44 patients diagnosed with breast cancer or lymphoma, who started chemotherapy treatment at the Instituto de Oncología y Radiobiología of Cuba, from February 2017 to April 2018. Primary and secondary methods were used for raw data collection and several statistical tests were used for its analysis. Results: The mean age and treatment period were 47.7 years old and 5.05 months, respectively. The most prevalent risk factor was high blood pressure and cardiotoxicity was higher (27.8%) in patients with previous diastolic dysfunction. Among those who developed cardiotoxicity, the variable that showed the greatest affectation was global longitudinal strain (p<0.0001), with a reduction of 19.6% with respect to the basal one. Conclusions: Global longitudinal strain is an echocardiographic index of myocardial performance, which presented a significant discriminating value with respect to cardiotoxicity in patients who received chemotherapeutic treatment.

Utilidad de las técnicas de deformación miocárdica (strain) para evaluar cardiotoxicidad en pacientes con enfermedades oncológicas y tratamiento quimioterápico / Usefulness of myocardial strain techniques to assess cardiotoxicity in patients with oncologic diseases undergoing chemotherapy

RESUMEN Introducción: La evaluación de la función miocárdica es fundamental para la toma de decisiones durante el seguimiento de pacientes con enfermedades oncológicas que reciben quimioterapia. Con las técnicas de speckle-tracking bidimensional se puede determinar el grado de deformación de la fibra miocárdica y obtener una medida más directa de la función sistólica que la que aporta la fracción de eyección del ventrículo izquierdo (FEVI). Objetivo: Evaluar la función miocárdica, mediante ecocardiografía, en pacientes con enfermedades oncológicas y tratamiento quimioterápico. Método: Se realizó un estudio descriptivo longitudinal prospectivo en 21 pacientes con diagnóstico de enfermedad oncoproliferativa e indicación de quimioterapia con trastuzumab, en el Hospital de Fuerteventura (España), entre enero de 2017 y mayo de 2020. A todos se les realizó ecocardiograma transtorácico con técnica de speckle-tracking (strain longitudinal global) antes del tratamiento y durante el seguimiento. Resultados: Predominaron las mujeres (95,2%) con diagnóstico de cáncer de mama (90,5%) y la edad promedio fue de 53,8 años (rango 38-75). La FEVI y el strain longitudinal global fueron normales (100%) antes del inicio de la quimioterapia. Fue necesario suspender el tratamiento en 3 pacientes (14,3%); pero solo en 2 de ellos (9,5%) por cardiotoxicidad detectada por ecocardiografía. Cinco pacientes (23,8%) presentaron síntomas de insuficiencia cardíaca, 1 (4,8%) tenía cardiotoxicidad y en los otros 4 (19,0%) se demostró ausencia de disfunción miocárdica, por lo que se pudo continuar el tratamiento con seguridad. Conclusiones: El ecocardiograma con técnica de speckle-tracking bidimensional fue de vital importancia para evaluar la función miocárdica y guiar el tratamiento quimioterápico en pacientes con enfermedades oncológicas.

ABSTRACT Introduction: Assessment of myocardial function is critical for decision making during the follow-up of patients with oncologic diseases undergoing chemotherapy. Two-dimensional speckle-tracking techniques help to determine the degree of myocardial fiber deformation and provide a more direct measure of systolic function than left ventricular ejection fraction (LVEF). Objective: To evaluate myocardial function by means of echocardiography in patients with oncological diseases undergoing chemotherapy. Methods: A prospective longitudinal descriptive study was performed in 21 patients diagnosed with cancer and with indication for chemotherapy with trastuzumab, in the Hospital of Fuerteventura (Spain), between January 2017 and May 2020. All underwent transthoracic echocardiography with speckle-tracking technique (global longitudinal strain) before treatment and during follow-up. Results: Women (95.2%) with a diagnosis of breast cancer (90.5%) predominated and the mean age was 53.8 years (range 38-75). Left ventricular ejection fraction and global longitudinal strain were normal (100%) before starting chemotherapy. It was necessary to suspend treatment in 3 patients (14.3%); but only in 2 of them (9.5%) due to cardiotoxicity detected by echocardiography. Five patients (23.8%) presented symptoms of heart failure, 1 (4.8%) had cardiotoxicity and in the other 4 (19.0%) the absence of myocardial dysfunction was demonstrated, so that treatment could be continued safely. Conclusions: Two-dimensional speckle-tracking echocardiography was of vital importance for assessing myocardial performance and guiding chemotherapy in patients with oncologic diseases.

Prevention of doxorubicin-induced Cardiotoxicity by pharmacological non-hypoxic myocardial preconditioning based on Docosahexaenoic Acid (DHA) and carvedilol direct antioxidant effects: study protocol for a pilot, randomized, double-blind, controlled trial (CarDHA trial).

BACKGROUND: Anthracycline-induced cardiotoxicity (AIC), a condition associated with multiple mechanisms of damage, including oxidative stress, has been associated with poor clinical outcomes. Carvedilol, a ß-blocker with unique antioxidant properties, emerged as a strategy to prevent AIC, but recent trials question its effectiveness. Some evidence suggests that the antioxidant, not the ß-blocker effect, could prevent related cardiotoxicity. However, carvedilol's antioxidant effects are probably not enough to prevent cardiotoxicity manifestations in certain cases. We hypothesize that breast cancer patients taking carvedilol as well as a non-hypoxic myocardial preconditioning based on docosahexaenoic acid (DHA), an enhancer of cardiac endogenous antioxidant capacity, will develop less subclinical cardiotoxicity manifestations than patients randomized to double placebo. METHODS/DESIGN: We designed a pilot, randomized controlled, two-arm clinical trial with 32 patients to evaluate the effects of non-hypoxic cardiac preconditioning (DHA) plus carvedilol on subclinical cardiotoxicity in breast cancer patients undergoing anthracycline treatment. The trial includes four co-primary endpoints: changes in left ventricular ejection fraction (LVEF) determined by cardiac magnetic resonance (CMR); changes in global longitudinal strain (GLS) determined by two-dimensional echocardiography (ECHO); elevation in serum biomarkers (hs-cTnT and NT-ProBNP); and one electrocardiographic variable (QTc interval). Secondary endpoints include other imaging, biomarkers and the occurrence of major adverse cardiac events during follow-up. The enrollment and follow-up for clinical outcomes is ongoing. DISCUSSION: We expect a group of anthracycline-treated breast cancer patients exposed to carvedilol and non-hypoxic myocardial preconditioning with DHA to show less subclinical cardiotoxicity manifestations than a comparable group exposed to placebo. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN69560410. Registered on 8 June 2016.