Indices used to assess for LVSD
| Measure | Strengths | Limitations | Threshold for significant LVSD | Recommendation for use | |
|---|---|---|---|---|---|
| LVFS | |||||
 | • Long historical precedent • Easy to acquire and measure | • Highly angle dependent • Poor reliability (~7% error when in the normal range)30 | <24%a | Adjunct measure only except in the setting of inadequate windows for alternate measures | |
| LVEF | |||||
 | Teichholz formula (from linear dimensions) | • Easy to acquire and measure | • Significant geometric assumptions • Inaccurate | <50%a | Not recommended |
| 2D echo (5/6 area length or biplane Simpson's method) | • Standard across most laboratories • Established utility in heart failure | • Geometric assumptions • Measurement error • Only ~50% sensitivity to detect LVSD in comparison with CMRI (in survivor data) | May be used as primary screening | ||
| 3D echo | • Better reproducibility • 53%–68% sensitivity to detect LVSD in comparison with CMRI (in survivor data) | • Requires specialized training and equipment • Limited data in younger children | Preferred for primary screening in adolescents and young adults, when available | ||
| CMRI | • Optimal LVEF reproducibility and accuracy • Can measure other potentially important cardiac features (eg, precise measurement of mass; edema, fibrosis) | • Requires specialized training and equipment • Less availableb • Compliance challenges in younger childrenb • An improvement in outcomes has not been demonstrated in adult cardio-oncology populations • Limited pediatric cardio-oncology data | Secondary evaluation as indicatedb | ||
| GLS | |||||
 | • More sensitive measure of cardiac function • Prognostic of subsequent LVEF declines37 | • An improvement in outcomes has not been demonstrated in adult cardio-oncology populations39 • Limited pediatric cardio-oncology data | >−16% (approximate)42 or ≥15% worsening from baseline valuec | Adjunct measure only (further study needed) | |
| Measure | Strengths | Limitations | Threshold for significant LVSD | Recommendation for use | |
|---|---|---|---|---|---|
| LVFS | |||||
| • Long historical precedent • Easy to acquire and measure | • Highly angle dependent • Poor reliability (~7% error when in the normal range)30 | <24%a | Adjunct measure only except in the setting of inadequate windows for alternate measures | |
| LVEF | |||||
| Teichholz formula (from linear dimensions) | • Easy to acquire and measure | • Significant geometric assumptions • Inaccurate | <50%a | Not recommended |
| 2D echo (5/6 area length or biplane Simpson's method) | • Standard across most laboratories • Established utility in heart failure | • Geometric assumptions • Measurement error • Only ~50% sensitivity to detect LVSD in comparison with CMRI (in survivor data) | May be used as primary screening | ||
| 3D echo | • Better reproducibility • 53%–68% sensitivity to detect LVSD in comparison with CMRI (in survivor data) | • Requires specialized training and equipment • Limited data in younger children | Preferred for primary screening in adolescents and young adults, when available | ||
| CMRI | • Optimal LVEF reproducibility and accuracy • Can measure other potentially important cardiac features (eg, precise measurement of mass; edema, fibrosis) | • Requires specialized training and equipment • Less availableb • Compliance challenges in younger childrenb • An improvement in outcomes has not been demonstrated in adult cardio-oncology populations • Limited pediatric cardio-oncology data | Secondary evaluation as indicatedb | ||
| GLS | |||||
| • More sensitive measure of cardiac function • Prognostic of subsequent LVEF declines37 | • An improvement in outcomes has not been demonstrated in adult cardio-oncology populations39 • Limited pediatric cardio-oncology data | >−16% (approximate)42 or ≥15% worsening from baseline valuec | Adjunct measure only (further study needed) | |
The table depicts the derivations of imaging-based measures of left ventricular systolic function. LVFS is the fractional change in cavity diameter during the cardiac cycle. LVEF is the fractional change in cavity volume during the cardiac cycle. Strain is the fractional change in myocardial fiber length, or deformation, during the cardiac cycle, typically derived from speckle-tracking analysis of 2D echocardiographic images. GLS is the average deformation in the longitudinal dimension. 2D or 3D echocardiographic derivations of LVEF should be the primary screening measure used to assess for LVSD during pediatric AML therapy. Strengths, limitations, and recommendations for use are based on general cardiovascular-imaging quantification guidelines and adult cardio-oncology guidelines, with additional supportive references listed within the table and footnotes.29,32,34,40
LVFS and LVEF cutoffs are based on grade 2 severity events for the terms “left ventricular systolic dysfunction” and “ejection fraction decreased” in the National Cancer Institute Common Terminology Criteria for Adverse Events (Versions 3.0 and 5.0, respectively). Precise cutoffs may vary among treatment protocols, and clinicians should consult the specific protocol for further guidance.
Some indications for CMRI in secondary evaluation are poor echocardiographic windows resulting in inadequate assessment of function, borderline/indeterminate echocardiographic results in which a more precise LVEF estimate would change clinical management, or baseline or significant LVSD to evaluate for underlying cardiomyopathy.31,32 CMRI does not employ ionizing radiation, and assessment of LV volumes, mass, and LVEF does not require intravenous contrast. However, younger children require sedation/anesthesia to complete CMRI, which is an important consideration.43 Increasing availability coupled with ongoing technological improvements that reduce motion artifacts/patient compliance demands, scanning time, and postprocessing time may result in increased CMRI use in pediatric cancer populations in the future.
GLS values are typically expressed as a negative percentage; less negative values reflect worse systolic function (eg, −16% is worse than −18%). The limit of normal has not been precisely established in pediatrics; the reported limit of −16% is an imprecise estimate based on prior pediatric studies.42 The worsening of 15% from the baseline value is based on adult cardio-oncology guidelines and refers to the percent worsening from the baseline value,32 not the absolute worsening in GLS (eg, a change from −20% to −17% is a 15% worsening). LVEDD, left ventricular end-diastolic diameter; LVEDV, left ventricular end-diastolic volume; LVESD, left ventricular end-systolic diameter; LVESV, left ventricular end-systolic volume.