Cardio-Oncology Echocardiography Protocol for Anthracyclines, Trastuzumab

Dobson R, Ghosh AK, Ky B, et al.
BSE and BCOS Guideline for Transthoracic Echocardiographic Assessment of Adult Cancer Patients Receiving Anthracyclines and/or Trastuzumab. JACC CardioOncol 2021;3:1-16.

The following are key points to remember from the British Society of Echocardiography (BSE) and British Cardio-Oncology Society (BCOS) guideline for transthoracic echocardiographic assessment of adult cancer patients receiving anthracyclines and/or trastuzumab:

  1. Cardio-oncology is a relatively new and rapidly developing subspecialty which aims to prevent, detect, monitor, and treat cardiac complications in patients with cancer or receiving cancer therapy.
  2. Transthoracic echocardiography is the key diagnostic tool for screening, surveillance, and detection. Cancer therapy–related cardiac dysfunction (CTRCD) is a common occurrence, especially in patients receiving anthracyclines (e.g., doxorubicin, epirubicin, daunorubicin, and idarubicin) and/or human epidermal growth factor receptor 2 (HER2)-targeted therapy (trastuzumab, or Herceptin). BSE and BCOS recently published guidelines which define cardiotoxicity, outline a standard echocardiographic protocol for the assessment of left ventricular (LV) function, and provide guidance for referral and management. All patients should undergo comprehensive baseline echocardiography with additional cardio-oncology specific measurements including: two-dimensional (2D) and three-dimensional (3D) volumes, 2D and 3D LV ejection fraction (LVEF), global longitudinal strain (GLS), right ventricular (RV) size, and systolic function assessment.
  3. LV systolic function assessment:
    • Estimating LVEF is not supported.
    • 2D volumetric Simpson's is recommended, preferably from measurements in two planes (apical four- and two-chamber). Endocardial surface should be traced at end-diastole and end-systole, excluding papillary muscles and trabeculation.
    • 3D LVEF assessment allows for more precise contouring of the actual shape of the LV cavity and does not rely on the geometric assumptions 2D LVEF assessment does. As such, 3D LVEF reportedly has superior reproducibility compared to 2D LVEF. However, it remains very sensitive to image quality.
    • When two contiguous LV segments from any apical view are not adequately seen, contrast is recommended, and should then be used in all sequential testing. Given its unknown effects on 2D speckle tracking, contrast images should be obtained after strain images.
  4. Since diastolic dysfunction can precede systolic dysfunction, full diastolic assessment should be done at baseline and all sequential imaging.
  5. GLS through speckle-tracking echocardiography:
    • Strain, or deformation, refers to the change in length of the myocardium between relaxation and contraction. It is quantified by dedicated speckle tracking software which tracks different regions of myocardium based on their unique speckle patterns. Longitudinal strain is the degree of deformation from base to apex, with more negative values indicating greater deformation.
    • While circumferential and radial strain may also be impaired in CTRCD, most clinical data thus far support the use of longitudinal strain. GLS is obtained from all three standard apical views. The two visible contours should outline the endocardial border and epicardial border with the region of interest aligned as accurately as possible to obtain the 17-segment LV model.
    • While normal GLS varies with age, sex, loading conditions, and different software vendors, a normal GLS is typically defined as more negative than -17% for males and -18% for females. Thus, a sequential change in GLS from -22% to -18% is considered significant, as it reflects a >15% change and is known to predict subsequent decline in LVEF.
  6. Right heart assessment is being incorporated now as more evidence suggests that RV abnormalities are of prognostic significance.
  7. Baseline risk stratification of cardiotoxicity depends on both the proposed therapy agent, dose, and duration, as well as patient-related risk factors (female sex, age >65 years, presence of traditional cardiovascular risk factors, prior reduced LVEF, chronic kidney disease, elevated B-type natriuretic peptide [BNP] and/or proBNP).
  8. Frequency of monitoring varies widely across different guidelines. Typically, during active treatment, echocardiography is recommended every 3 months, while post-treatment surveillance can range between 1 and 5 years. This depends on patient-specific risk factors and whether or not the patient developed CTRCD during cancer treatment.
  9. Cardiotoxicity definitions by echocardiography:
    • Definite cardiotoxicity: a decline in 2D/3D LVEF by >10% (absolute percentage points) to a value <50%
    • Probable subclinical cardiotoxicity: a decline in 2D/3D LVEF by >10% to a value ≥50% with an accompanying decrease in GLS >15%
    • Possible subclinical cardiotoxicity: a decline in 2D/3D LVEF <10% to a value <50%, OR
    • LV GLS: a relative percentage reduction in GLS by >15% from baseline
  10. If GLS is not concordant with low LVEF, cardiac magnetic resonance imaging may be considered.
  11. Referral to a dedicated cardio-oncology service is recommended in patients with decreased baseline LVEF prior to treatment and those who develop CTRCD (both symptomatic and asymptomatic). Goal-directed medical therapy with angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers and beta-blockers should be initiated for possible, probable, and definite cardiotoxicity. However, there is no evidence at present to hold cancer therapy based on decreased strain alone.

Clinical Topics: Cardio-Oncology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound, Magnetic Resonance Imaging

Keywords: Anthracyclines, Cardiotoxicity, Diagnostic Imaging, Diastole, Echocardiography, Heart Failure, Magnetic Resonance Imaging, Natriuretic Peptide, Brain, Neoplasms, Renal Insufficiency, Chronic, Risk Assessment, Risk Factors, Secondary Prevention, Stroke Volume, Systole, Ventricular Function, Left

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