Effects of pentoxifylline in patients with chronic Chagas cardiomyopathy: A randomized, double-blind, controlled pilot trial

TL;DR

A clinical trial tested pentoxifylline in patients with chronic Chagas cardiomyopathy and found some improvements in inflammation and quality of life, but no significant changes in heart function.

Contribution

This is the first pilot trial to investigate pentoxifylline's effects on inflammatory markers and quality of life in chronic Chagas cardiomyopathy patients.

Findings

Pentoxifylline showed a trend toward reducing TNF-α and increasing IL-10 levels, though not statistically significant.

Quality of life improved significantly in the pentoxifylline group.

No significant changes in left ventricular function or myocardial perfusion were observed.

Abstract

Chronic Chagas cardiomyopathy (CCC) is a major public health issue in endemic areas of Latin America, representing one of the leading causes of heart failure and sudden death. The hallmark histopathological lesion of CCC is low-intensity, persistent myocarditis associated with cytokine production. Long-term use of pentoxifylline (PTX) may serve as an effective pharmacological intervention for immunomodulation, reducing inflammation and, consequently, diminishing myocardial perfusion abnormalities and thus preserving left ventricular systolic function.

We investigated 38 patients with CCC, randomly assigned to PTX (n = 19), 400 mg 3 times a day for 6 months, or placebo (PLC) (n = 19). At baseline and post-treatment, patients underwent cytokine measurements, quality of life assessment, 2D echocardiography, and myocardial perfusion scintigraphy. After treatment, TNF-α levels in the PTX group decreased from 10.14 ± 5.5 to 8.32 ± 3.6 and from 9.12 ± 4.4 to 10.32 ± 8.5 in the PLC group (p = 0.06). Additionally, IL-10 levels increased from 2.74 ± 0.7 to 5.61 ± 8.6 in the PTX group, while in the placebo group, they decreased from 6.96 ± 11.8 to 5.50 ± 8.3 (p = 0.09); neither of these findings reached statistical significance. Also, no significant changes were observed in the echocardiographic variables after treatment. LVEF showed a modest change from 46.2% ± 7.9 to 47.4% ± 7.0 in the PTX group and from 48.2% ± 6.6 to 48.0% ± 6.9 in the PLC group (p = 0.37). No significant positive effects on myocardial perfusion were noted. However, the quality-of-life assessment documented a significant improvement of functional capacity in the PTX group.

The results of this study suggest a potential positive effect of PTX in modulating the inflammatory profile of CCC patients. However, use of pentoxifylline in these patients did not attenuate the degree of ventricular dysfunction or reduce myocardial perfusion defects.

Chagas disease remains a neglected tropical disease, despite affecting millions of people. Among its clinical forms, chronic Chagas cardiomyopathy (CCC) is the most frequent and severe. This condition progresses slowly and often results in heart failure, leading to high rates of illness and death. Despite decades of research, significant gaps remain in our understanding of the mechanisms driving disease progression and the development of effective treatments. Currently, there are no therapies specifically designed for CCC; patients are treated with drugs commonly used for other heart diseases, which may not adequately address the unique features of Chagas-related heart damage. We have been working to understand how inflammation and abnormalities in myocardial perfusion contribute to the progressive loss of heart function in CCC. We conducted a clinical study to evaluate whether a drug with immune-modulating properties could offer clinical benefits. Over a six-month treatment, we observed improvements in inflammatory markers and patients’ reported quality of life. However, we didn’t observe significant changes in left ventricular function or myocardial perfusion. The improvements in inflammatory profile and quality of life suggest a potential role for immunomodulation in managing CCC. These findings highlight the complexity of CCC and emphasize the need for therapeutic approaches. Continued research into targeted treatments is essential to improve outcomes for patients with this neglected and serious condition.

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