190 Poster Display IV. Drug therapy, other each with EF < 40% on an ACE inhibitor or ARB and a beta-blocker, ± diuretics. Patients in cohorts 1 and 2 receive 2-hr infusions, consisting of 3 escalating doses of CK-452 and a placebo treatment randomized into the sequence to maintain blinding, each occurring at least 1 week apart. In Cohort 1, the median Cmax at each dose was 93, 177, and 355 ng/mL; predicted cohort 2 Cmaxs are 320, 500, and 650 ng/mL. Infusions up to 72 hrs will be studied in cohorts 3-5. Results: Data from cohort 1 indicate Doppler derived SET and stroke volume (SV) measured during the 2nd hour of infusion were the most sensitive indicators of drug effect. At plasma concentrations of 177 and 355 ng/mL, SET increased by 22 (p = 0.04) and 53 msec (p < 0.001), respectively. At 355 ng/mL, SV increased by 10 mL (p = 0.07). Both LV end systolic and end diastolic volumes appeared to decrease at 355 ng/mL, by 16 and 26 ml, respectively. Heart rates and blood pressures were unchanged. There were no treatment related adverse events on active study drug and no adverse events at the highest dose. Pharmacokinetics were very similar to those in healthy volunteers. Data from cohorts 2 and 3 will be available at the time of presentation. Conclusions: These data confirm CK-452 is active in heart failure pa- tients. The first 2 cohorts will establish tolerability and pharmacodynamic response to CK-452 in stable heart failure patients over a broad range of plasma concentrations. Data from this first Phase II trial may support translation of this novel and unique mechanism into populations with more severe heart failure. 738 Hemodynamic effects of ivabradine, a pure heart rate lowering agent, in patients with severe systolic chronic heart failure receiving beta-blockers G. Jondeau 1 , M. Bohm 2 , L. Tavazzi 3 , A. Voors 4 1 Paris, France; 2 Homburg, Germany; 3 Pavia, Italy; 4 Groningen, Netherlands Purpose: Ivabradine is a novel heart rate (HR) lowering agent which acts by specifically and selectively inhibiting the sinoatrial pacemaker If current. This study evaluates the effects of ivabradine on HR, blood pressure (BP), and left ventricular (LV) volumes and function in patients with severe systolic chronic heart failure (CHF) (Class III or IV NYHA, LV Ejection Fraction (LVEF) less 35%, previous hospitalisation for HF within 12 months), all receiving conventional background therapy, in- cluding beta-blockers (100%) or RAS agent (99%). Methods: patients with HR >60 bpm received oral ivabradine for 6 weeks, with an up titration from 2.5 to 7.5 mg bid according to HR reduction and clinical tolerability. Clinical follow-up, ECG and echocar- diography - to assess LV end diastolic volume (LVEDV), end systolic volume (LVESV) and LVEF - were performed at baseline and at the end of the treatment period. Results: Mean age was 62±13 years. Patients were class III (93%) or class IV (7%) NYHA. Approximately 60% of the patients received at least half of the target dose of beta-blockers, 17.2% received the target dose. The main reason for not achieving the target dose of beta-blockers was hypotension (57%). Most patients (65.5%) were up titrated to the highest ivabradine dose (7.5 mg b.i.d.), including 60% of those receiving the target dose of beta-blockers. Table 1 n Beaseline, mean±SD Change, mean±SD 95% CI p-value HR, bpm 87 74.1±10.4 -10.1±11.1 12.5;-7.8 p<0.001 LVEF, % 85 28.6±5.4 +5.3±6.1 4.0;6.6 p<0.001 LVEDV, ml 81 223.8±81.5 -8.2±37.5 -16.5;0.1 p=0.053 LVESV, ml 80 161.7±60.6 -18.5±30.0 -25.2;-11.8 p<0.001 SBP, mmHg 86 120.8±15.3 -0.2±15.7 DBP, mmHg 86 75.1±9.1 -1.1±10.9 Clinical symptoms were improved in 66.7% of the patients according to the investigator and a decrease of at least one NYHA class was observed in 52% of them. Ivabradine was well tolerated. Conclusion: In patients with chronic systolic HF in NYHA functional class III and IV already receiving beta-blockers, the addition of ivabra- dine significantly reduces HR, is safe and improve LV function. These results suggest a potential benefit of the co-administration of ivabradine with beta-blockers in patients with severe CHF. 739 Role of calcium channel blockers in preventing heart failure in hypertensive and coronary artery disease patients P. Costanzo, M. Petretta, C. Marciano, T. Losco, F. Marsico, O. Scala, D. Ruggiero, P. Perrone-Filardi, M. Chiariello Federico II University, Cardiovascular sciences, Naples, Italy Purpose: Current evidence indicates safety and efficacy of calcium chan- nel blockers (CCBs) on cardiovascular outcomes. However, doubts still remain about the risk of developing heart failure associated with CCBs. In particular, previous overviews showed an increased risk of heart failure associated with CCBs compared to other drugs and a lack of protection compared to placebo. Nevertheless, the last available overview included trials published up to June 2003 and since then the results of eight prospective, large trials have been published. Thus, the aim of this study was to update the role of CCBs in preventing heart failure in hypertensive and coronary artery disease patients Methods: We performed a meta-analysis including 21 trials that com- pared a CCB with another drug or placebo/top of therapy and that assessed heart failure. Metaregression analysis was performed to assess the relationship between achieved blood pressure difference and heart failure odds ratio. We included 139133 patients. Results: The risk of heart failure was increased by CCBs based regimen compared to non-CCBs active treatment (OR 1.20; 95% CI 1.09 to 1.32; comparison p<0.0001; heterogeneity p=0.03). ACE-is decreased the risk of heart failure compared to CCBs (OR 1.20; 95% CI 1.09 to 1.33; comparison p<0.0001; heterogeneity p=0.8). However CCBs decreased the risk of heart failure compared to placebo (OR 0.72; 95% CI 0.59 to 0.87; comparison p<0.001; heterogeneity p=0.8). Moreover, CCBs decreased the risk of heart failure in CAD patients (OR 0.76; 95% CI 0.60 to 0.95; comparison p=0.01; heterogeneity p=0.44). Conclusions: Despite previous overviews, we found a protective effect of CCBs than placebo (decreased risk by 28%), influenced by the blood pressure reduction. Furthermore, our evidence suggests a beneficial role for CCBs in preventing heart failure in the subgroup of coronary artery disease patients. 740 IV Iron without erythropoietin improves cardiac functional parameters evaluated by echocardiography in patients with heart failure and anemia J. Toblli 1 , A. Lombrana 1 , P. Duarte 2 , F. Di Gennaro 1 1 Hospital Aleman, Laboratory of Experimental Medicine, Buenos Aires, Argentina; 2 CEMIC, Haematology, Buenos Aires, Argentina Patients with iron deficiency anemia (IDA) congestive heart failure (CHF) and chronic kidney disease (CKD) present fatigue, breathless- ness, and reduced exercise capacity, which lead to a decrease in quality of life. The correction of IDA can improve this condition. However, the exact relationship between anemia and in particular iron deficiency and the cardiac functions is still unclear. In this study, we evaluated echocardiographic parameters (EP) and their relation with serum fer- ritin (SF) in patients with CHF, CKD and IDA who received IV iron versus placebo. Forty pts. Hb g/dl<12.5 (men) and <11.5 (women); TSAT<20%; SF<100ng/ml; CrCl<90ml/min and LVEF<35% were di- vided into two equal groups. Group A with a weekly infusion of isotonic saline solution (ISS) and group B with Iron Sucrose Complex (ISC) for 5 weeks. SF and EP were evaluated at baseline (BL) and at 6 months (6m). Patients did not receive EPO throughout the study. Results (mean±SD): 1-Hb (A vs. B) BL: 10.2±0.5 vs. 10.3±0.6; 6m: