Abstract 2004: Early and Late Effects of Cardiac Resynchronization Therapy upon Force-Frequency Relation and Calcium Regulatory Gene Expression in Heart Failure Patients
Background: Congestive Heart Failure is associated with a blunted force frequency response (FFR). We investigated whether the beneficial hemodynamic effects of cardiac resynchronization therapy (CRT) are associated with an acute and chronic improvement of this blunted FFR.
Methods: Twenty heart failure patients (NYHA class ≥ 3) underwent echocardiographic examination within two days after CRT implantation (BL) and four months later (FU) during incremental AAI and DDD-CRT pacing at 70, 90 and 110 bpm, each step for 4 minutes. FFR was determined from the ratio of the left ventricle (LV) systolic pressure/end systolic volume index at given heart rate. In a subgroup of six patients, serial gene expression levels for LV sarcoplasmatic reticulum calcium ATPase2α (SERCA2α) and phospholamban (PLN) were measured using rt-PCR.
Results: The FFR during DDD-CRT pacing was higher at all heart rates as compared to AAI and was paralleled by a decrease in dyssynchrony at BL (p<0.01). At FU, a greater upward shift of the FFR was noticed in DDD-CRT as compared to AAI (p<0.01). In addition, CRT was associated with a significant force frequency amplification at FU as evidenced from the steeper slope of the FFR relationship (p=0.039). The improvement in FFR was associated with a significant upregulation of both LV SERCA2α (p=0.04) and PLN message (p=0.04) levels as well as their ratio (p=0.03).
Conclusion: CRT was associated with an acute upward shift in the FFR related to restored synchronicity. At FU, CRT was associated with a further improvement in the FFR with significant force frequency amplification in parallel to upregulation of calcium regulatory genes.