Introduction:
Heart failure (HF) continues to be a common cause of morbidity and mortality and dilated cardiomyopathy (DCM) is a common cause of adverse ventricular remodeling and HF. Left ventricular assist device (LVAD) has emerged as an important mode of therapy for advanced HF by unloading the LV and maintaining systemic perfusion. The extent to which LVAD mediates beneficial remodeling in the right ventricle (RV) is incompletely understood.
Hypothesis:
Differential mRNA expression in a chamber-specific manner may elucidate LVAD mediated functional reverse remodeling in end-stage HF.
Methods and Results:
Right (RV) and left (LV) ventricle tissue from explanted failing and non-failing control (NFC) human hearts were collected within 20 mins of explantation. Global mRNA expression profiling in DCM patients without (n=8; 7M/1F; age 42-54 years; ejection fraction (EF): 17.5% (15-26%) and with (n= 8; 7M/1F; age 44-58 yrs; EF 15% (12.5-25.0%) LVAD (HeartMate II) was compared to NFC (n=6; age 39-56 yrs; 4M/2F). mRNA microarray was performed using Affymetrix PrimeView gene chips and evaluated using the
Ingenuity Pathway Analysis (
IPA) program. LVAD use was associated with marked reduction of myocardial hypertrophy, interstitial fibrosis and apoptosis in both the LV and RV. The cleaved caspase-3 and Tunnel-positive cardiomyocytes were reduced in both RV and LV with LVAD. Total gene entities of 991 in the LV and 860 in the RV were differentially expressed in hearts with DCM without LVAD. LVAD use was independently associated with the altered regulation of 280 genes in the LV and 380 genes in the RV. The total up/down regulated genes involved in cardiac hypertrophy ranged from 20-60% and myocardial fibrosis ranged from 10-80% and were altered in both the RV and LV in response to LVAD therapy. In addition, 14-30% of the total apoptotic-related genes and 6-20 % of the cytokine-related genes were changed in both ventricles.
Conclusions:
LVAD reduced pathological hypertrophy and fibrosis in both LV and RV and is correlated with altered gene expression controlling adverse myocardial remodeling and fibrosis, apoptotic and inflammatory pathways. LVAD therapy represents a viable long-term therapy for HF patients and is associated with improved RV remodeling.
Effects of pump speed changes on exercise capacity in patients supported with a left ventricular assist device—an overview
