Key result
High-dose anthracycline exposure (≥300 mg/m2) in childhood cancer survivors with preserved EF was associated with increased LV wall stress compared to low-dose exposure (66.7 vs 56.6 g/cm2; P<0.01).
Why the study?
Does high-dose anthracycline exposure cause dose-dependent changes in echocardiographic markers of LV dysfunction in asymptomatic childhood cancer survivors with preserved EF?
Cross-Sectional (n=200)
Blinded to risk status
Does high-dose anthracycline exposure cause dose-dependent changes in echocardiographic markers of LV dysfunction in asymptomatic childhood cancer survivors with preserved EF?
Childhood cancer survivors with preserved EF 10+ years after anthracycline exposure exhibit dose-dependent subclinical changes in echocardiographic markers of LV dysfunction.
May signal early LV remodeling in high-risk survivors; hypothesis-generating for combined echo-biomarker screening pending prospective validation.
PURPOSE: To examine the utility and reliability of obtaining early echocardiographic measurements of left ventricular (LV) remodeling as well as blood biomarkers of cardiac injury in asymptomatic childhood cancer survivors at risk for LV dysfunction and congestive heart failure due to past exposure to anthracycline chemotherapy. EXPERIMENTAL DESIGN: Using a cross-sectional design, anthracycline-exposed childhood cancer survivors with preserved ejection fraction (EF; ≥50%) were evaluated using early echocardiographic indices and blood biomarkers of LV dysfunction. Survivors treated with ≥300 mg/m(2) anthracyclines [high risk (HR): n = 100] were compared with those treated with <300 mg/m(2) anthracyclines [low risk (LR): n = 50] and matched healthy controls (HC: n = 50). All echocardiograms were interpreted by an institutional cardiologist and a study cardiologist blinded to risk status. RESULTS: Time from diagnosis was comparable for HR (12.0 years) and LR (13.2 years, P = 0.8) survivors. Echocardiograms: HR had lower LV thickness-dimension ratio (Z-score: HR: -0.62, LR: -0.03, HC: -0.02; P < 0.001), increased LV wall stress (HR: 66.7 g/cm(2), LR: 56.6 g/cm(2), HC: 54.2 g/cm(2); P < 0.01), and higher myocardial performance index (HR: 0.51, LR: 0.46, HC: 0.46; P < 0.01). Interobserver correlation (clinical/blinded reading) for all echocardiographic indices was excellent (range: R = 0.76-0.97, P < 0.001). Blood biomarkers: With the exception of NT-proBNP (r = 0.28, P < 0.01), there was no correlation between blood biomarkers (B-type natriuretic peptide, Troponin-T, ST-2, Galectin-3) and LV dysfunction. CONCLUSION: Childhood cancer survivors with preserved EF 10+ years from anthracycline exposure had dose-dependent changes in echocardiographic markers of LV dysfunction.
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Armenian et al. (2014) conducted a cross-sectional in Childhood cancer survivors at risk for LV dysfunction (n=200). High-dose anthracycline exposure (≥300 mg/m2) vs. Low-dose anthracycline exposure (<300 mg/m2) and healthy controls was evaluated on LV wall stress (g/cm2) (p=<0.01). High-dose anthracycline exposure (≥300 mg/m2) in childhood cancer survivors with preserved EF was associated with increased LV wall stress compared to low-dose exposure (66.7 vs 56.6 g/cm2; P<0.01).
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