Cardiac Dysfunction after Stem Cell Transplantation: Can Peritransplant Cardiac Troponin-I Predict Future Issues?

Cardiac dysfunction is an increasingly recognized long-term complication of pediatric stem cell transplant (SCT) with incidence reported between 10-25%. Patients with mild left ventricular systolic dysfunction (LVSD) may be asymptomatic, though can progress to overt congestive heart failure. Cardiac biomarkers hold promise to detect early cardiac injury. We hypothesized that early cardiac Troponin-I (cTn-I) elevation may predict LVSD within the first 100 days after SCT. Echocardiography screening was performed prior to SCT (baseline), at T+30, and T+ 100 as part of routine clinical care. We evaluated cTn-I in 45 SCT patients: 12 with newly detected LVSD in the first 100 days after SCT; 13 with new borderline LVSD; 7 with LVSD prior to HSCT that remained stable through the first 100 days post SCT; and 13 consecutive controls with normal LV function before and after SCT. We evaluated cTn-I using Luminescent Oxygen Channeling Immunoassay, at six time periods: prior to transplant (baseline), day 0, 7, 14, 21, and 49. cTn-I was considered elevated if concentration was ≥0.03 ng/mL. Demographic data were abstracted from patient records (Table 1). At day T+7, patients with new LVSD were more likely to have elevated cTn-I than controls (6/12 vs. 1/13, p=0.03) (Figure 1). Among all 262 samples tested, cTn-I elevation ≥0.03 ng/mL occurred in 95 (36.3%), and 32 of 45 patients (71.1%) had at least one sample with elevated cTn-I. Among patients with new LVSD, the first ‘rise’ in cTn-I appears to occur at day T+7 (Figure 2). Cyclophosphamide preparative chemotherapy and GFR<80 mL/min/1.73 m2 during the first 100 days (measured by Cystatin C) were both associated with new LVSD (8/12 v 2/13 p=0.02; 10/12 v. 3/13 p<0.01, respectively), whereas previous anthracycline use was not (8/12 v 5/13, p=0.24). cTn-I elevation is common in the peri-transplant period, raising the possibility of direct cardiac injury from chemotherapy, particularly cyclophosphamide, perhaps identifying a group that would benefit from increased cardiac surveillance. Early intervention in patients with cTn-I rise after stem cell transplant may improve outcomes. Further studies are ongoing to determine if additional cardiac biomarkers such as nt-proBNP and Glycogen Phosphorylase BB may aid in predicting LVSD and delineate the specific time and cause of cardiac injury. Table 1DemographicsDemographicNew LVSD n= 12Control n= 13New borderline LVSD n=13Preexisting LVSD n=7Total n=45Age (median, range)15.0 ( 0.5-25.8)5.5 (0.9-17)10.9 (2.7-3 2.8)10.4 (1.1-23.3)10.9 (0.5-32.8)Female (%)17%23%38%43%29%Malignant (%)67%46%46%57%53%Allogeneic (%)83%69%77%86%78%Myeloablative (%)67%62%54%43%58%MSD/MUD (%)25%/50%38%/31%31%/54%29%/57%29%/47% Open table in a new tab Figure 2cTn-l in New LV Systolic Dysfunction (by Subject)View Large Image Figure ViewerDownload Hi-res image Download (PPT)