Assessment of late cardiomyopathy by magnetic resonance imaging in patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and idarubicin

Abstract

Late cardiomyopathy CMP is regarded as a potential severe long-term complication after anthracycline-based regimens for acute promyelocitic leukaemia (APL). We assess by MRI the incidence and severity of clinical and subclinical long-term CMP in a cohort of adult APL patients in first complete remission with PETHEMA trials. Adult patients diagnosed with APL in first complete remission lasting ≥2 years underwent anamnesis and physical examination and were asked to perform a cardiac MRI. Clinical CMP was defined as radiographic and physical signs of heart failure accompanied by symptoms or by left ventricle ejection fraction (LVEF) <45% by MRI with or without symptoms. Subclinical CMP was defined as the following MRI abnormalities: LVEF 45-50% or late gadolinium enhancement or two or more of LVEF ≤55%, left ventricle end-diastolic volume index ≥98 ml/m, left ventricle end-systolic volume index ≥38 ml/m, right ventricle end-diastolic volume index ≥106 ml/m and regional wall motion abnormalities. Of the 82 patients enrolled in the study, median cumulative dose of anthracyclines (doxorubicin equivalence) was 650 mg/m, and median time from APL diagnosis to the study was 87 months (range, 24-195). Seven out of 57 patients with available MRI (12%) had subclinical CMP (all of them showed late gadolinium enhancement in MRI), and none had clinical CMP. Among the 25 patients without MRI, none had CMP by chest X-ray and physical assessment. In summary, we found 12% of subclinical and no clinical late CMP assessed by MRI in APL patients treated with PETHEMA protocols. Due to the low number of patients, we must interpret our results cautiously.

Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology

“…As an alternative to echocardiography, a cardiac MRI can also be performed, for example, to overcome restrictive sonographic conditions. While the detection of reduced LVEF should initiate heart failure therapy even in asymptomatic patients, the significance of changes in cardiac MRI such as late gadolinium enhancement remains to be elucidated [82,117]. The prognostic significance of biomarkers in asymptomatic long-term cancer survivors is likewise poorly understood [5].…”

Accuracy of a Novel Handheld Wireless Platform for Detection of Cardiac Dysfunction in Anthracycline-Exposed Survivors of Childhood Cancer

“…Importantly, in both studies, LV EF as measured by 2D echocardiography was on average 5% higher than that measured by CMR, providing further confirmation that LV EF measurements obtained from these two modalities are not comparable. For the current study, abnormal LV EF was defined as <45%, which is an established CMR-based threshold in oncology (19)(20)(21) and nononcology populations (22)(23)(24). Per our data, a CMR-based threshold of LV EF <45% would also correspond to an echocardiogram-based measurement of LV EF <50%, a cutoff used to define LV systolic dysfunction per the common terminology of adverse events (CTCAE version 4; !grade 2 toxicity).…”

“…Sensitivity, specificity, false-negative rate, and false-positive rates were calculated to assess the accuracy of the Vivio as well as echocardiography for detection of abnormal LV EF as measured by CMR (gold standard). The cutoff for abnormal (LV EF < 45% by CMR) was per established thresholds in oncology (19)(20)(21) and nononcology populations (22)(23)(24), as it is a clear indicator for referral to a cardiologist for clinical assessment. Multivariable logistic regression analysis was performed to examine the risk of abnormal LV EF (<45%), as measured by the Vivio, according to cumulative anthracycline dose (<250 mg/m 2 , !250 mg/m 2 ) and adjusted for clinically relevant covariates [age at diagnosis, sex, time since completion of therapy, chest radiotherapy exposure (any), body mass index (BMI), and cardiovascular risk factors (hypertension, diabetes, and dyslipidemia)].…”

Incidence and Risk Factors for Development of Cardiac Toxicity in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia

“…As serial echocardiogram monitoring was not performed in our study, some low-LVEF events may have been missed, especially in asymptomatic patients. In this regard, a study by Rodríguez-Veiga et al analyzed late cardiomyopathy via longitudinal assessment using magnetic resonance imaging in 82 patients with acute promyelocytic leukemia treated with anthracycline-containing regimens, showing 12% had developed subclinical cardiomyopathy [ 26 ].…”