BACKGROUND: Heart rate reduction (HRR) improves left ventricular (LV) filling, 
increases myocardial O2 supply, and reduces myocardial O2 consumption, which are 
all beneficial in congestive heart failure (CHF). However, the long-term effects 
of HRR on cardiac function and remodeling are unknown.
METHODS AND RESULTS: We assessed, in rats with CHF, the effects of long-term HRR 
induced by the selective I(f) current inhibitor ivabradine (as food admix for 90 
days starting 7 days after coronary artery ligation). To assess intrinsic 
modifications of LV tissue induced by long-term HRR, all parameters were 
reassessed 3 days after interruption of treatment. Ivabradine decreased heart 
rate over the 90-day treatment period (-18% versus untreated at 10 mg x kg(-1) x 
d(-1)), without modifying blood pressure, LV end-diastolic pressure, or 
dP/dt(max/min). Ivabradine significantly reduced LV end-systolic but not 
end-diastolic diameter, which resulted in preserved cardiac output due to 
increased stroke volume. In the Langendorff preparation, ivabradine shifted LV 
systolic but not end-diastolic pressure-volume relations to the left. Ivabradine 
decreased LV collagen density and increased LV capillary density without 
modifying LV weight. Three days after interruption of treatment, the effects of 
ivabradine on LV geometry, shortening, and stroke volume persisted despite 
normalization of heart rate.
CONCLUSIONS: In rats with CHF, long-term HRR induced by the selective I(f) 
inhibitor ivabradine improves LV function and increases stroke volume, 
preserving cardiac output despite the HRR. The improvement of cardiac function 
is related not only to the HRR per se but also to modifications in the 
extracellular matrix and/or function of myocytes as a consequence of long-term 
HRR.