Abstract 15761: Improving RBC K Uptake and Its Impact on Myocardial Ischemia and Electrical Regeneration of the Heart: A Novel Therapeutic Approach
Introduction: Since red-blood cell K (RBCK) plays a key role on Hb-O2/CO2 exchanges, we tested the hypothesis that increasing RBCK improves myocardial-O2. Aim: to evaluate the effect of a new composition of Amiloride (AM) on RBCK and its impact in CHD patients.
Methods: 63 patients (70% males,63±7old, BP 140±7/80±14) with CHD (angina 76%, MI 66%, 3-vessel disease 79%, and HF 48%) entered a randomized double-blind (Phase I-12month) trial of AM (5 mg/QD) vs Placebo (34 vs 29) in subjects receiving Optimal Medical Therapy (OMT), followed by open-label (Phase II, 12-m) comparison AM+ OMT vs OMT alone. Both phases were intention-to-treat. Cardiovascular studies: serial ECG, Echo, Ion Transport study (intracellular and extracellular Na/K, ionized Ca++), Duke Treadmill Score (DTS), and non-invasive cardiac, aortic, systemic vascular and brachial vascular hemodynamic (DynaPulse) were obtained. Statistical analysis by SAS, p<0.05 was considered significant.
Results: (Phase I): At 1-Month, compared to placebo, 87% of subjects on AM had increased RBCK (92.1±6 vs 80.9±5.7mmol/lc,p2.0E.06), with significant reduction (79.4%) in angina class (1.6±0.7 vs 3.1±0.8, p1.0E-07), ST-T alterations (41%) and HF symptoms (35%) vs less angina (21%), and unchanged ST-T and HF in placebo. At 2-M, compared to placebo, subjects on AM showed significant improvement of DTS (7.9±4.2 vs −4.75±4.4, p8.1E-08), increased exercise time (7.9±2.8 vs 5.3±2.5 min, p<0.05) and predicted low risk subjects (64% vs 18%,p0.0035). At 6-M, compared to placebo, subjects on AM had low recurrence of angina (17 vs 46%), whereas ST-T waves normalized in 34%, improved in 43%, and was unchanged in 14%. No improvement of ST-T occurred with placebo. Phase II: In AM group, no CV events were reported in phase I-II, and 8 patients (24%) exhibited evidence of electrical regeneration (new R-voltage) on previous inactive myocardial zones. In OMT group significant recurrence of angina (46%), and CV events (44.8%) were reported in both phases, including ACS(5), MI (2), CVA(2), Pacemaker(2) and Arrhythmia(4).
Conclusions: These results strongly support that a therapeutic approach directed to improve and preserve RBC K-exchange reverses angina, ST-T alterations, and induces electrical regeneration of the heart.
- © 2010 by American Heart Association, Inc.