Abstract
Background and Aim: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.Patients and Methods: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.Results: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.Conclusions: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.
Highlights
There is a strong evidence supporting a pathophysiological role for the xanthine oxidase (XO) pathway in heart failure.[2]
A relatively new Doppler index of combined systolic and diastolic myocardial performance of the left ventricle, defined as the sum of the isovolumetric contraction time and isovolumetric relaxation time (IRT) divided by ejection time, has been reported.[4,5]
Patients with elevated serum uric acid (SUA) responded favorably to allopurinol whereas those with SUA less than 7 mg/dL exhibited a trend toward no change
Summary
Most epidemiological studies associate increasing serum uric acid (SUA) with increased cardiovascular event rate and Access this article online. A relatively new Doppler index of combined systolic and diastolic myocardial performance of the left ventricle, defined as the sum of the isovolumetric contraction time and IRT divided by ejection time, has been reported.[4,5]. This index is obtained, reproducible, has a narrow range in normal subjects, does not depend on LV geometry, and correlates with invasive obtained measures of systolic and diastolic cardiac function.[6] This index has been reported to be simple and independent of heart rate and blood pressure. Two-tailed values of P < 0.05 were considered significant
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