Abstract 3483: Management of Hyperphosphatemia Is an Important Novel Therapeutic Target in Chronic Heart Failure
Cardiovascular diseases are frequently associated with chronic kidney disease (CKD), which is important because individuals with CKD are more likely to die of cardiovascular disease than renal failure. On the other hand, hyperphosphatemia is found in the majority of patients with end-stage renal disease. Recent studies have also documented that hyperphosphatemia is associated with cardiovascular diseases and increases both mortality and morbidity. Interestingly, we found hyperphosphatemia in patients with chronic heart failure and a significant positive correlation between serum phosphate levels and plasma BNP levels. Therefore, we tested whether precipitated calcium carbonate (a phosphate binding agent), a drug for hyperphosphatemia, mediates beneficial effects on left ventricular dysfunction in the canine pacing-induced heart failure model. In beagle dogs, we induced heart failure by 6 weeks of rapid right ventricular pacing at 230 bpm using a pacemaker with or without precipitated calcium carbonate at a daily oral dose of 100mg during forth to sixth week (n=6 each in treated and untreated groups). Neither blood pressure (104 ± 6 vs 106 ± 5 mmHg, ns) nor heart rate (120 ± 10 vs 121 ± 4 /min, ns) at basal conditions differed between the groups treated with and without precipitated calcium carbonate 6 weeks after the onset of the study. Left ventricular ejection fraction increased (48.5 ± 2.0 % vs 29.0 ± 1.8 %, p<0.05), and both mean pulmonary arterial pressure (15.8 ± 1.2 mmHg vs 24.0 ± 2.1 mmHg, p<0.05) and pulmonary capillary wedge pressure (12.2 ± 2.1 mmHg vs 17.3 ± 2.3 mmHg, p<0.05) decreased in the precipitated calcium carbonate-treated group compared with the untreated group. The administration of precipitated calcium carbonate decreased plasma phosphate levels compared with the untreated group (3.5 ± 0.3 mg/dL vs 4.5 ± 0.5 mg/dL, p<0.05) along with the tendency of the reduction of plasma iPTH levels. Thus, we conclude that the reduction of serum phosphate levels is beneficial for the pathophysiology of chronic heart failure and may provide an important novel therapeutic target in patients with chronic heart failure. The release of PTH following high plasma phosphate levels may be involved because PTH is known to modulate cardiovascular systems.