Hematopoietic cell transplantation (HCT

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 EF (≥50%) were evaluated using early echocardiographic indices and blood biomarkers of LV dysfunction. Survivors treated with ≥300mg/m2 anthracyclines (high-risk [HR]: n=100) were compared with: i) those treated with <300 mg/m2 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 (12.0y) and LR (13.2y, 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/cm2, LR: 56.6 g/cm2, HC: 54.2 g/cm2; p<0.01) and higher myocardial performance index (HR: 0.51, LR: 0.46, HC: 0.46; P<0.01). Inter-observer 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 (BNP, 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.

Measures of long-term cardiovascular risk were associated with conditions that are more common in pediatric liver transplant recipients than nontransplanted peers, namely, diastolic hypertension and glucose intolerance. Larger, longitudinal studies are warranted to investigate whether cIMT could be useful for stratifying these patients' cardiovascular risk-and potential need for proactive intervention-during long-term follow-up.

Childhood cancer survivors are at high risk of developing congestive heart failure (CHF) compared to the general population, and there is a dose-dependent increase in CHF risk by anthracycline dose. The mechanism by which this occurs has not been fully elucidated. Metabolomics, the comprehensive profile of small-molecule metabolites, has the potential to provide insight into the pathogenesis of disease states and discover diagnostic markers for therapeutic targets. We performed echocardiographic testing and blood plasma metabolomic analyses (8 pathways; 354 metabolites) in 150 asymptomatic childhood cancer survivors previously treated with anthracyclines. Median time from cancer diagnosis to study participation was 12.4 years (2.6–37.9 years); 64% were treated for a hematologic malignancy; median anthracycline dose was 350 mg/m2 (25–642 mg/m2). Thirty-five (23%) participants had cardiac dysfunction – defined as left ventricular end-systolic wall stress >2SD by echocardiogram. Plasma levels of 15 compounds in 3 metabolic pathways (carbohydrate, amino acid, and lipid metabolism) were significantly different between individuals with cardiac dysfunction and those with normal systolic function. After adjusting for multiple comparisons, individuals with cardiac dysfunction had significantly lower plasma carnitine levels (relative ratio [RR]: 0.89, p<0.01) in relation to those with normal systolic function. These findings may facilitate the development of primary prevention (treatment of carnitine deficiency prior to/ during anthracycline administration) and secondary prevention strategies (screening and treatment in long-term survivors) in patients at highest risk for CHF.