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Left ventricular diastolic filling patterns associated with progressive anthracycline-induced myocardial damage: A
F A Bu'Lock1, M G Mott, A Oakhill
1Departments of Paediatric Cardiology and Oncology, Bristol Royal Hospital for Sick Children, St. Michael's Hill, Bristol, BS2 8BJ, United Kingdom.
Insights
Anthracycline chemotherapy in children can cause early, reversible changes in diastolic function, but these do not strongly predict later heart damage or failure. Long-term implications remain uncertain due to individual variability.
Area of Science:
- Cardiology
- Pediatric Oncology
- Pharmacology
Background:
- Anthracyclines are crucial chemotherapy agents for childhood cancers.
- Cardiotoxicity is a significant concern with anthracycline use, particularly affecting left ventricular function.
- Understanding early changes in diastolic function is vital for monitoring and managing potential cardiac damage.
Purpose of the Study:
- To investigate the evolution of left ventricular diastolic function during anthracycline treatment in pediatric patients.
- To assess the relationship between early diastolic changes and subsequent myocardial damage or cardiac failure.
- To determine the clinical implications of altered diastolic filling patterns in this population.
Main Methods:
- Prospective, sequential Doppler echocardiography in 125 children receiving anthracyclines.
- Serial measurements of diastolic filling parameters (E, A, EA ratio, EDecT, IVRT) and systolic function (SF).
- Comparison of serial data with matched controls and assessment of correlation with cumulative anthracycline dose.
Main Results:
- Progressive myocardial damage was indicated by a decrease in fractional shortening (SF) of 1% per 100 mg/m² of anthracycline.
- Early anthracycline exposure (1-100 mg/m²) led to decreased EA ratio and prolonged isovolumic relaxation time (IVRT), which often normalized.
- Significant diastolic abnormalities were observed in 20% of patients by treatment end, with considerable individual variability; early diastolic changes did not strongly predict reduced SF.
Conclusions:
- Anthracycline therapy in children induces modest, often reversible, changes in left ventricular diastolic filling patterns.
- While some patients develop significant diastolic abnormalities, their predictive value for reduced systolic function or clinical outcomes is uncertain.
- Further research is needed to clarify the long-term pathophysiological and clinical significance of these early diastolic alterations.
Abstract:
The objective of this study was to examine changes in diastolic function associated with progressive myocardial damage and their implications. We used prospective sequential Doppler echocardiographic studies of left ventricular (LV) function. The study included 125 consecutive children (median age 6.3 years) receiving anthracyclines to cumulative doses between 45 and 1150 mg/m2 (median 270 mg/m2). We measured peak early (E) and atrial (A) phase filling velocities, EA ratio, deceleration and isovolumic relaxation times (EDecT and IVRT), heart rate, and fractional shortening (SF). Results were compared serially and with individually paired control data matched for body surface area. Progressive myocardial damage was evidenced by a mean SF decrease of 1 absolute %/100 mg/m2 of anthracycline. Six patients developed cardiac failure. After 1-100 mg/m2 of anthracyclines, the EA ratio decreased (mean 1.54-1.40, p = 0.02) and IVRT became prolonged (54 vs 52 msec in controls, p = 0.03). EA ratio increased again with the next dose, usually normalizing thereafter. Twelve patients ended treatment with an EA ratio <1 (1 cardiac death) and 17 with EA ratio >2 (2 cardiac deaths). Diastolic abnormalities were not strongly predictive of reduced SF. Modest changes in left ventricular diastolic filling patterns occur during anthracycline treatment of childhood malignancies. Although 20% of patients have significant abnormalities of diastolic filling by the end of treatment, considerable individual variability renders the pathophysiological and clinical implications of the early changes uncertain.
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