Abstract 15482: Recovery of Histone Methylation and Cardiac Function by Prolonged Left Ventricular Assist Device Support, Predominantly by Pulsatile Flow Device, in Advanced Heart Failure
Background: It was reported that pulsatile flow left ventricular assist device (PF-LVAD) is more likely to induce reverse remodeling of the LV than continuous flow one (CF-LVAD), while underlying mechanism remains unclear. Epigenetic modification such as histone methylation has been suggested to be an important upstream signal to determine function and/or fate of cardiac tissue. We hypothesized that histone methylation may be associated with reverse LV remodeling under the LVAD support, dependent upon the type of the LVAD.
Methods: This study enrolled 15 patients (7 PF-LVAD and 8 CF-LVAD) who institutionally completed “bridge-to-transplantation” by 2.7±1.2 years and 2.0±0.7 years of the LVAD support, respectively. Transmural tissue of the LV apex was sampled at the time of the LVAD implant and the transplant surgery.
Results: Ejection fraction predominantly increased in the PF-LVAD group, compared to that in the CF-LVAD group (18.4±9.4% to 28.1±11.1% vs 17.6±3.8% to 16.6±4.0%, P <0.05). Plasma BNP was reduced to a significantly greater extent in the PF-LVAD group than the CF-LVAD group (1,284±668 pg/ml to 175±211 pg/ml vs 733±525 pg/ml to 218±229 pg/ml, P <0.05). Histological analysis revealed that, H3K9 di-methylation (H3K9me2) and H3K9 tri-methylation (H3K9me3) were significantly recovered in the cardiomyocytes of the both groups. However, change of H3K9me2 and H3K9me3 were significantly more striking in the PF-LVAD group (H3K9me2; 60.3% ±7.6% to 73.0±8.7% and H3K9me3; 61.0±7.5% to 74.8±5.0% of the total myocytes) compared to the CF-LVAD group (H3K9me2; 64.4±6.4% to 72.4±7.0% and H3K9me3; 67.4±4.1% to 76.7±3.2% of the total myocytes). Interestingly, the increase of H3K9me3 expression was significantly correlated with plasma BNP levels in the both groups (CF-LVAD; R =-0.6905, P <0.05 vs PF-LVAD; R =-0.786, P <0.05) and they were significantly more striking in the PF-LVAD group compared to the CF-LVAD.
Conclusion: Functional recovery in advanced cardiac failure occurred predominantly under the PF-LVAD support compared to that under the CF-LVAD support, in association with recovery of histone methylation in the LV cardiomyocytes, suggesting that pulsatile flow is important in reverse LV remodeling at least in part via epigenetic modification.
Author Disclosures: E. Ito: None. S. Miyagawa: None. S. Fukushima: None. Y. Yoshikawa: None. S. Saito: None. K. Domae: None. A. Harada: None. M. Takeda: None. K. Toda: None. Y. Sawa: None.
- © 2016 by American Heart Association, Inc.