Regular paperEffects of pentoxifylline on cytokine profiles and left ventricular performance in patients with decompensated congestive heart failure secondary to idiopathic dilated cardiomyopathy☆
Section snippets
Study design and patient enrollment:
This study was approved by the Committee for Research on Human Subjects of the University of the Witwatersrand. Eighteen consecutive newly diagnosed, untreated black patients with idiopathic dilated cardiomyopathy were recruited for this single-center, prospective, double-blind, randomized, placebo-controlled study. All patients were ≥18 years of age, had class IV heart failure, a left ventricular ejection fraction ≤40% as determined by radionuclide ventriculography, a left ventricular
Baseline characteristics:
There were no differences in the baseline characteristics between study groups (Table 1). Moreover, the mean dose and duration of administration of quinapril, furosemide, digoxin, and dobutamine did not differ between the groups (data not shown).
Side effects:
Administration of pentoxifylline was well tolerated. No side effects were noted.
assessment of the degree of cytokine activation:
Compared with patients with class II to III heart failure and with normal subjects, plasma cytokine and Fas/Apo-1 concentrations were markedly elevated in the patients with
Discussion
This is the first study of the administration of a cytokine-modulating agent in patients with severe, decompensated heart failure. The main finding of the present study is that in association with alterations in the proinflammatory cytokine, TNF-α, and the apoptosis-signaling receptor, Fas/Apo-1, pentoxifylline administration resulted in an improved left ventricular pump function in patients with advanced heart failure.
In accordance with the findings of other studies, we found markedly
References (16)
- et al.
Proinflammatory cytokine levels in patients with depressed left ventricular ejection fractiona report from the Studies of Left Ventricular Dysfunction (SOLVD)
J Am Coll Cardiol
(1996) - et al.
Basic mechanism in heart failurethe cytokine hypothesis
J Cardiac Failure
(1996) - et al.
Cytokines as emerging targets in the treatment of heart failure
Trends Cardio Med
(2000) - et al.
TNF-induced cardiomyopathy
Lancet
(1990) - et al.
Randomised investigation of effects of pentoxifylline on left ventricular performance in idiopathic dilated cardiomyopathy
Lancet
(1998) - et al.
Molecular cloning and expression of the Fas ligand, a novel member of the tumour necrosis factor family
Cell
(1993) - et al.
Independent and incremental prognostic value of Doppler-derived mitral deceleration time of early filling in both symptomatic and asymptomatic patients with left ventricular dysfunction
J Am Coll Cardiol
(1996) - et al.
Cytokine network in congestive heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy
Am J Cardiol
(1999)
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2021, Biomedicine and PharmacotherapyCitation Excerpt :The use of pentoxifylline as an immunomodulatory agent with pump-improving function in mild-to-moderate HF has been investigated in several other clinical trials as well [52,54–56]. With the exception of a neutral outcome in one trial [54], the addition of pentoxifylline to the conventional treatment of HF (digoxin, angiotensin-converting enzyme inhibitors, and a beta blocker) has improved LVEF, functional outcome, and plasma inflammatory markers in patients with idiopathic dilated [52,55] and ischemic [56] cardiomyopathy. Intravenous immunoglobulin (IVIG) has also been assessed for therapeutic efficacy in the treatment of patients with chronic HF and dilated cardiomyopathy due to its immunomodulatory effects [57,58].
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This study was supported by the H.E. Griffin Charitable Trust and the University of the Witwatesrand Research Council, Johannesburg, South Africa.