Routine serial echocardiography in systolic heart failure: is it time for the heart failure guidelines to change?

The authors sought to obtain objective evidence for impacting the American College of Cardiology Heart Failure Guidelines for the routine use of serial echocardiography by assessing the reliability of the use of clinician-assessed patient symptoms and New York Heart Association (NYHA) functional classification compared with ejection fraction (EF) measured by echocardiography. A prospective study in 256 patients with systolic heart failure (HF) enrolled into an HF disease management program with EF ≤40% and at least 2 annual echocardiograms were included. Only 86 of 256 (33.5%) patients were correctly classified by NYHA class as showing improvement, no change, or deterioration as compared with echocardiographic assessments. Patients whose NYHA class showed no change between echocardiograms had the lowest survival rate. Quantification in patient's status with NYHA classification is not always a reliable assessment to evaluate prognosis and guide medical therapy for patients with systolic HF

Interleukin-4 Modulates the Inflammatory Response in Ifosfamide-Induced Hemorrhagic Cystitis

We investigated whether interleukin-4 (IL-4) is present and capable of reducing inflammatory changes seen in ifosfamide-induced hemorrhagic cystitis. Male Swiss mice were treated with saline or ifosfamide alone or ifosfamide with the classical protocol with mesna and analyzed by changes in bladder wet weight (BWW), macroscopic and microscopic parameters, exudate, and hemoglobin quantification. In other groups, IL-4 was administered intraperitoneally 1 h before ifosfamide. In other experimental groups, C57BL/6 WT (wild type) and C57BL/6 WT IL-4 (-/-) knockout animals were treated with ifosfamide and analyzed for changes in BWW. Quantification of bladder IL-4 protein by ELISA in control, ifosfamide-, and mesna-treated groups was performed. Immunohistochemistry to tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) as well as protein identification by Western blot assay for inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was carried out on ifosfamide- and IL-4-treated animals. In other experimental groups, antiserum against IL-4 was given 30 min before ifosfamide. In IL-4-treated animals, the severity of hemorrhagic cystitis was significantly milder than in animals treated with ifosfamide only, an effect that was reverted with serum anti-IL-4. Moreover, knockout animals for IL-4 (-/-) exhibit a worse degree of inflammation when compared to C57BL/6 wild type. Exogenous IL-4 also attenuated TNF-alpha, IL-1 beta, iNOS, and COX-2 expressions in ifosfamide-treated bladders. IL-4, an anti-inflammatory cytokine, attenuates the inflammation seen in ifosfamide-induced hemorrhagic cystitis.National Research Council of Brazil (CNPq)National Research Council of Brazil (CNPq)CAPESCAPESFundacao Cearense de Amparo a Pesquisa (FUNCAP), CearaBrazilFundacao Cearense de Amparo a Pesquisa (FUNCAP), Ceara-Brazi

Cyclooxygenase-2 expression on ifosfamide-induced hemorrhagic cystitis in rats

Purpose Hemorrhagic cystitis (HC) is a limiting side effect of chemotherapy with ifosfamide (IFS). In this study, we investigated the participation of cyclooxygenase-2 (COX-2) upon ifosfamide-induced HC. Methods Male Wistar rats (150-200 g; six rats per group) were treated with saline, IFS (400 mg/kg, i.p.) and analyzed by changes in bladder wet weight, macroscopic and microscopic parameters, and COX-2 expression. In other groups etoricoxib (selective COX-2 inhibitor), indomethacin (non-selective COX inhibitor), thalidomide (selective TNF-alpha inhibitor), pentoxifyllin (non-selective TNF-alpha inhibitor) were added 1 h before IFS administration. The classical protocol using three doses of Mesna was also evaluated and compared with two extra doses of etoricoxib or indomethacin. Results COX-2 was expressed significantly 24 h after IFS administration mainly in myofibroblasts and mast cells evaluated by immunohistochemistry. Treatment 1 h before IFS injection with etoricoxib, indomethacin, thalidomide, and pentoxifylline reduced COX-2 expression and some macroscopic and microscopic parameters in IFS-induced HC. Moreover, addition of etoricoxib or indomethacin with the last two doses of Mesna was more efficient than three doses of Mesna alone when evaluated microscopically. Conclusions COX-2 participates in the pathogenesis of IFS-induced HC and the treatment with COX and TNF-alpha inhibitors reduced COX-2 expression. The addition of COX-inhibitors to the last two doses of Mesna represents a new therapeutic strategy of preventing HC.National Research Council of Brazil (CNPq), CAPES and Fundação Cearense de Amparo a Pesquisa (FUNCAP), Ceará-Brazil, for financial support