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      Effects of Thalidomide Treatment in Heart Failure Patients

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          Background: Several studies have reported a direct association between elevated plasma levels of inflammatory cytokines and worse functional class (New York Heart Association [NYHA]) and cardiac function, measured as left ventricular ejection fraction (LVEF). Thalidomide has recently shown to improve LVEF in chronic heart failure patients, accompanied by a marked decrease in plasma levels of tumor necrosis factor alpha (TNF-α). Methods: In a randomized prospective open label study of men and women with heart failure (HF) due to ischemic and non-ischemic cardiomyopathy who had systolic dysfunction (LVEF <40%) and NHYA classification, functional classes II and III were assigned to control (without thalidomide, 60 patients) or thalidomide group (20 patients). The initial dose of thalidomide was 100 mg once a day, and it was increased to 100 mg twice a day after a period of 10 days, if the prior dosage was well-tolerated. Demographic characteristics, etiology of HF, prior myocardial infarction, co-morbidities associated were registered and laboratory routine test, TNF-α serum levels, and echocardiogram were obtained at the beginning and after 6 months of follow-up. Results: Clinical status (NYHA) at the end of the follow-up period, improved moderately in both groups. TNF-α levels were initially of 5.88 ± 0.9 and 6.49 ± 1.82 vs. 6.32 ± 1.6 and 7.94 ± 3.8 pg/ml during follow-up, for thalidomide and control groups, respectively. There were non-significant differences in echocardiography variables. Conclusion: In conclusion, although there is a large amount of information supporting a direct relationship between TNF-α and worsening of symptoms and prognosis in patients with HF and recently, the beneficial effect on thalidomide treatment has been suggested, these preliminary observations should be confirmed in a larger prospective study, specially trying to clarify the action mechanisms.

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          Most cited references 23

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          Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD).

          This study sought to assess proinflammatory cytokine levels in patients in the studies of left ventricular dysfunction trial (SOLVD) in relation to both their New York Heart Association functional classification and their neurohormonal status before randomization. Elevated levels of tumor necrosis factor-alpha have been identified in 30% to 40% of patients with heart failure. However, it is unclear which subsets of patients with heart failure elaborate tumor necrosis factor-alpha. It is also unclear what the mechanism for the increased expression of proinflammatory cytokines is. Tumor necrosis factor-alpha and interleukin-6 levels were analyzed by enzymes-linked immunoassay using randomly selected plasma samples from patients in functional classes I to III who were enrolled in neurohormonal substudies of the SOLVD trial; age-matched healthy subjects served as the control group. Plasma levels of tumor necrosis factor-alpha (p < 0.001) were elevated in patients in functional classes I to III ([mean +/- SD] 1.95 +/- 0.54, 2.63 +/- 0.48, 6.4 +/- 1.9 pg/ml, respectively) compared with age-matched control subjects (0.75 +/- 0.05 pg/ml) and were progressively elevated in relation to decreasing functional status of the patient. Plasma levels of interleukin-6 (p < 0.001) were elevated in patients in functional classes I to III (3.3 +/- 0.55, 6.2 +/- 1.1, 5.22 +/- 0.9 pg/ml, respectively) compared with age-matched control subjects (1.8 +/- 0.5 pg/ml and were progressively elevated in relation to decreasing functional status of the patient. Cox proportional-hazards analysis showed that there was a trend toward significance between plasma tumor necrosis factor-alpha (p < 0.07) and survival, whereas there was no significant relation for plasma interleukin-6 (p < 0.72). Except for atrial natriuretic factor, which correlated weakly (r = 0.23, p = 0.04) with circulating tumor necrosis factor-alpha levels, there was no significance correlation between neurohormonal and proinflammatory cytokine levels. Circulating levels of proinflammatory cytokines increase in patients as their functional heart failure classification deteriorates. Moreover, activation of the neurohumoral axis is unlikely to completely explain the elaboration of proinflammatory cytokines in heart failure.
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            Guidelines for the diagnosis and treatment of chronic heart failure.

             ,  Espen Remme,  K Swedberg (2001)
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              ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure).


                Author and article information

                S. Karger AG
                November 2007
                09 November 2006
                : 108
                : 4
                : 237-242
                aHeart Failure Clinic, bImmunology and Rheumatology Department, cCardiology Department of Instituto Nacional de Ciencias Médicas y Nutrición ‘Salvador Zubirán’, and dInstituto Nacional de Cancerología, México City, Mexico
                96829 Cardiology 2007;108:237–242
                © 2007 S. Karger AG, Basel

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                Page count
                Tables: 5, References: 35, Pages: 6
                Original Research


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