“…4 However, some studies have revealed that betablockers with ISA have no beneficial effect in patients with severe heart failure although they improve the clinical condition in mildly symptomatic patients. [9][10][11][12][13] The mechanism of the beneficial effect of beta-blocker treatment for heart failure remains unclear, but suppression of circulating cathecholamines leading to myocardial toxicity and myocardial dysfunction, restoration of -1-receptor downregulation and improvement of myocardial metabolism due to a reduction of heart rate and oxygen consumption have been postulated as possible mechanisms. 16 In a trial using various beta-blockers for heart failure, Swedberg et al indicated that alprenolol, nonselective and with ISA, caused deterioration in heart failure or provoked heart failure death, and had to be replaced by metoprolol without ISA for a beneficial effect.…”