Expression levels of cTnTs and TnI were modified in the heart of pediatric and adults heart failure (HF) patients after ventricular assist device (VAD) implant

Background: VAD represent a viable therapeutic option for both children and adult patients with Heart Failure (HF). At molecular level, mechanical unloading by VAD use leads to a significant gene expression changes. Four different isoforms of cardiac troponin T (cTnT) are observed during development of normal heart, fetal cTnT 1,2,4 isoforms and adult cTnT3 isoform. The fetal cTnT4 is re-expressed in failing heart. Similarly, the slow skeletal TnI (ssTnI) isoform is expressed in embryonic life, while its expression levels decreases after birth, when the adult isoform cTnI is expressed. Of note, fetal isoforms of both TnT and TnI show a higher Ca2+ sensitivity than adult isoforms, resulting in a higher myocardial force contractility. It is not known if VAD implant could induce changes in expression of Tn proteins in HF myocardium. Purpose: The aim of this study was to evaluate the effects of VAD treatment on the expression levels of cTnT isoforms, cTnI and ssTnI in cardiac muscle from both pediatric and adult patients with HF. Methods: Ten HF children [62±23 ms (mean±SD), 7 males, 23±4.5 LVEF%] and a group of 5 adult patients with HF [54±5.6 years, 5 males, 23.4±2.5 LVEF%] were enrolled. Patients from both groups were submitted to VAD implantation as bridge to cardiac transplantation. Cardiac biopsies were collected at VAD implant (Pre-VAD) and at the moment of heart transplantation (Post-VAD). Expression levels of cTnT 1,2,3 and 4 isoforms, cTnI and ssTnI were determined by real-time PCR. Results: In children, the mRNA expressions of fetal cTnT 1, 2, and fetal ssTnI do not change significantly after VAD implant, while the expression levels of cTnT3, fetal cTnT4 and cTnI increased (cTnT3: 0.16±0.03 vs 0.54±0.1; cTnT4: 0.15±0.032 vs 0.6±0.14; cTnI: 0.03±0.01 vs 0.07±0.012; Pre-VAD vs Post-VAD, p<0.05). In adults, the expression of all cTnT isoforms increased significantly after VAD implant, as well as cTnI (cTnT1: 1±0.13 vs 4.27±1.17; cTnT2: 1.08±0.18 vs 8.06±2.79; cTnT3: 0.88±0.9 vs 2.8±0.6; cTnT4: 0.866±0.09 vs 1.66±0.24; cTnI: 0.38±0.08 vs 5.06±1.75; Pre-VADvsPost-VAD p<0.01). Again in adult patients, the expression levels of ssTnI were measurable at Pre-VAD (0.58±0.38), but undetectable at Post-VAD. Comparison of Tn isoform expression levels between children and adults is reported in Figure 1. Significantly higher expression levels for all troponins were observed for adults compared with children, except for ssTnI.