Abstract 2017: Endomyocardial Upregulation of β1-Adrenoreceptor Gene Expression and Myocardial Contractile Reserve following Cardiac Resynchronization Therapy
BACKGROUND: Patients with end stage heart failure are characterized by a blunted myocardial contractile reserve (MCR) which is partly related to a downregulation of β1-adrenoreceptors (β1-AR). We investigated left ventricular (LV) contractile response to β-adrenergic stimulation immediately after (BL) and at four months (FU) following cardiac resynchronization therapy (CRT). Simultaneously BL and FU LV endomyocardial gene expression levels for β1-adrenoreceptors (β1-AR) were measured.
METHODS: Left ventricular dP/dt was invasively measured in 10 CHF patients (NYHA class ≥ 3; EF < 25%) during incremental AAI and CRT pacing at 70,90,110 and 130 bpm, with and without continuous infusion of intravenous dobutamine (DOB:5μg/kg/min) at BL and at FU. Serial left ventricular endomyocardial β1-AR gene expression was measured using quantitative reverse transcriptase polymerase chain reaction.
RESULTS: In the absence of DOB, CRT resulted in a significant upward shift of the force-frequency relation (FFR) at BL (p<0.01) as compared with AAI which was futher potentiated at FU. DOB not only shifted the FFR upwards but also increased the slope of the FFR (p<0.05) suggesting not only force augmentation but also force amplification. At FU the DOB induced augmentation was significantly higher compared to BL (p<0.01) and paralleled a significant upregulation of the β1-AR gene expression (p=0.02).
CONCLUSIONS: CRT is associated with an acute upward shift in FFR and with a recruitment in MCR which is clearly enhanced after four months. The restoration of the adrenergic control of the FFR at four months might be the result of CRT induced molecular remodeling with upregulation of β1-AR.