Những tác động này góp phần vào tình trạng quá tải chất lỏng và K cạn kiệt +. Sau đó là đặc biệt quan trọng trong dân số HF và / hoặc sau MI dân số đã gia tăng nguy cơ tử do tim đột ngột và thường được điều trị bằng các vòng lặp hoặc thuốc lợi tiểu thiazide cho sức mạnh K + | CHAPTER 10 HOW TO USE NEUROHORMONAL ANTAGONISTS IN HEART FAILURE 121 simultaneously secretion of K . These effects contribute to fluid overload and also K depletion. The latter is of particular importance in the HF population and or post-MI population who are already at increased risk of sudden cardiac death and who are often being treated with loop or thiazide diuretics that potentiate K loss. Local aldosterone production within the heart is believed to contribute to cardiac myocyte hypertrophy and interstitial fibrosis. An increase in the quantity of fibrous tissue in the heart decreases ventricular compliance and also by disturbing the homogeneity of electrical conduction creates a substrate for arrhythmias. In the vasculature aldosterone contributes to endothelial dysfunction by impairing acetylcholine and NO-mediated vasodilatation. It also increases vascular inflammation by recruiting macrophages and promoting monocyte infiltration of vessel walls. The discovery of aldosterone escape following treatment with RAS blockers raised the possibility that direct aldosterone blockade might provide incremental benefits and protection for the HF Aldosterone Blockade in Chronic Heart Failure Patients with LV Dysfunction The RALES trial evaluated the effects of spironolactone on all-cause mortality in patients with advanced HF symptoms and evidence of systolic dysfunction who were already receiving an ACE inhibitor as background Patients received spironolactone 25-50 mg qd or placebo in addition to contemporary therapy with diuretics 100 digoxin 75 and an ACE inhibitor 95 . However -blockers were used in only 10 of patients. The trial was terminated early after a 30 relative mortality reduction was reported in patients randomized to spironolactone. There was a 29 relative reduction in sudden cardiac death and 36 reduction in death due to progressive HF. The risk of severe hyperkalemia was low at 2 in this carefully monitored group. RALES proved
