Nasr Gamela, Maurice Cherine
Department of Cardiology, Suez Canal University, Ismailia, Egypt.
J Cardiovasc Dis Res. 2010 Oct;1(4):191-5. doi: 10.4103/0975-3583.74262.
Increased xanthine oxidase (XO) activity may contribute to heart failure pathophysiology. This study evaluated whether a XO inhibitor, allopurinol produces clinical and functional benefits in patients with New York Heart Association functional class III to IV heart failure due to systolic dysfunction receiving optimal medical therapy as estimated by global left myocardial function.
Fifty-nine patients with a diagnosis of chronic heart failure due to coronary heart disease or idiopathic dilated cardiomyopathy and 20 healthy controls who attended the outpatient clinic of cardiology were subjected to full echocardiographic study including left ventricular diastolic and systolic function, and the combined index of myocardial performance [Tei index: isovolumetric relaxation time (IRT) + isovolumetric contraction time (ICT)/ejection time (ET)]. Patients were randomized to allopurinol (300 mg/day) or placebo. Improvement at 36 weeks was assessed using a composite end point comprising global left cardiac function as well as heart failure morbidity and mortality.
The percentage of patients characterized as improved, unchanged, or worsened did not differ between those receiving allopurinol or placebo. Allopurinol reduced serum uric acid (SUA) by 1.5 mg/dL (P = 0.001). In a subgroup analysis, patients with elevated SUA (more than 7mg/ dL) responded favorably to allopurinol whereas those with SUA less than 7mg/dL exhibited a trend toward no change. In addition, SUA reduction to allopurinol correlated with favorable clinical and functional response. Within the entire allopurinol patient cohort, those characterized as either improved or unchanged had significantly greater reductions in SUA compared with patients who did not change (P = 0.0007). In placebo patients, lower baseline SUA, but not change in SUA, correlated with improved clinical outcome.
Allopurinol did not produce significant clinical and functional improvement in unselected patients with moderate-to-severe heart failure. However, it is suggested that it is useful in patients with elevated SUA in a manner according to degree of SUA reduction. SUA may serve as a valuable biomarker to target heart failure therapy.
黄嘌呤氧化酶（XO）活性增加可能参与心力衰竭的病理生理过程。本研究评估了XO抑制剂别嘌醇对纽约心脏协会心功能Ⅲ至Ⅳ级、因收缩功能障碍接受最佳药物治疗（根据整体左心室功能评估）的心力衰竭患者是否具有临床和功能益处。
59例诊断为冠心病或特发性扩张型心肌病所致慢性心力衰竭的患者以及20例在心脏病门诊就诊的健康对照者接受了全面的超声心动图检查，包括左心室舒张和收缩功能以及心肌性能综合指标[Tei指数：等容舒张时间（IRT）+等容收缩时间（ICT）/射血时间（ET）]。患者被随机分为别嘌醇组（300mg/天）或安慰剂组。使用包括整体左心功能以及心力衰竭发病率和死亡率的复合终点评估36周时的改善情况。
接受别嘌醇或安慰剂治疗的患者中，改善、无变化或恶化的患者百分比无差异。别嘌醇使血清尿酸（SUA）降低了1.5mg/dL（P = 0.001）。在亚组分析中，SUA升高（超过7mg/dL）的患者对别嘌醇反应良好，而SUA低于7mg/dL的患者则呈现无变化趋势。此外，别嘌醇使SUA降低与良好的临床和功能反应相关。在整个别嘌醇患者队列中，改善或无变化的患者与未改变的患者相比，SUA降低幅度显著更大（P = 0.0007）。在安慰剂组患者中，较低的基线SUA与改善的临床结局相关，但SUA的变化与之无关。
别嘌醇对未选择的中重度心力衰竭患者未产生显著的临床和功能改善。然而，提示其对SUA升高的患者有用，且改善程度与SUA降低程度相关。SUA可能是心力衰竭治疗的一个有价值的生物标志物。
