Results of Targeted Anti–Tumor Necrosis Factor Therapy With Etanercept (ENBREL) in Patients With Advanced Heart Failure

Bozkurt, Biykem; Torre‐Amione, Guillermo; Warren, Marshelle; Whitmore, James B.; Soran, Özlem; Feldman, Arthur M.; Mann, Douglas L.

doi:10.1161/01.cir.103.8.1044

Cited by 356 publications

(198 citation statements)

References 7 publications

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“…Pilot studies suggested that etanercept was safe and provided improvement in quality of life, 6-minute walk distance, and ejection fraction in patients with HF. 30,31 Larger clinical trials, however, failed to show significant benefit of etanercept in HF. The Randomized Etanercept Worldwide Evaluation (RENEWAL) program, 3 in which 2048 patients were randomized to various regimens of etanercept vs placebo, was stopped early due to lack of therapeutic benefit.…”

Section: Modulation Of Inflammation In Hfmentioning

confidence: 99%

Inflammatory Biomarkers in Heart Failure

Petersen

Felker

2006

Congestive Heart Failure

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Multiple lines of evidence support the “cytokine hypothesis,” which suggests that inflammation plays an important role in the development and progression of heart failure. Circulating markers of inflammation, such as tumor necrosis factor α, interleukin 6, and C‐reactive protein, may be useful in establishing the diagnosis, gauging prognosis, and evaluating the response to therapy in patients with heart failure. In addition to their potential as heart failure biomarkers, inflammatory cytokines have been investigated as targets of heart failure therapy. Although results for therapies directed against specific cytokines (such as tumor necrosis factor α) have thus far been disappointing, multiple studies continue to address the therapeutic potential of modulating the immune response in heart failure. In this review, the authors analyze available data supporting the use of inflammatory markers both as biomarkers and as potential therapeutic targets.

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Section: Modulation Of Inflammation In Hfmentioning

confidence: 99%

Inflammatory Biomarkers in Heart Failure

Petersen

Felker

2006

Congestive Heart Failure

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“…9 In another study of human subjects with congestive heart failure, administration of soluble TNF-␣ receptors was associated with an improvement in LV remodeling, ie, reverse LV remodeling. 18 Recently, activation of matrix metalloproteinases (MMPs) was implicated in the pathogenesis of LV remodeling in congestive heart failure. 19,20 Moreover, TNF-␣ was shown to activate MMPs in the heart with subsequent LV remodeling, and treatment with TNF-␣-binding proteins resulted in reversal of LV remodeling.…”

Section: Tnf-␣ and LV Remodeling And Reverse Remodeling In Patients Wmentioning

confidence: 99%

Myocardial Proinflammatory Cytokine Expression and Left Ventricular Remodeling in Patients With Chronic Mitral Regurgitation

et al. 2003

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Background-In an animal model, stretch was shown to induce myocardial tumor necrosis factor-␣ (TNF-␣) expression.The purposes of this study were to determine whether the left ventricular (LV) volume overload that occurs in patients with chronic mitral regurgitation (MR) can induce myocardial and systemic TNF-␣ expression and whether there is a relationship between TNF-␣ expression and LV remodeling. Methods and Results-Plasma TNF-␣ and its receptors were measured before mitral valve (MV) repair surgery in 26 MR patients and 23Ϯ12 months after MV repair surgery in 9 MR patients. Myocardial mRNA copies of TNF-␣ were determined in 11 MR and 10 donor hearts using quantitative RT-PCR. Compared with 15 control subjects, pre-MV repair plasma TNF-␣ (3.59Ϯ1.81 versus 2.03Ϯ1.02 pg/mL, PϽ0.005) and its receptor levels were elevated in MR patients. Myocardial TNF-␣ mRNA copies (corrected for ␤-actin mRNA expression) in MR patients and donor hearts were 38.96Ϯ42.74ϫ10 6 and 0.88Ϯ0.75ϫ10 6 , respectively (Pϭ0.01). After MV surgery, there was a decrease in the plasma levels of TNF-␣ (2.79Ϯ1.14 versus 3.51Ϯ1.34 pg/mL, Pϭ0.02) and its receptors. There was a correlation between myocardial TNF-␣ expression and preoperative LV end-diastolic and end-systolic volumes. Moreover, there was an inverse correlation between myocardial TNF-␣ expression and regression in LV end-diastolic (rϭϪ0.76, Pϭ0.007) and end-systolic (rϭϪ0.73, Pϭ0.01) volumes after MV surgery. Conclusions-TNF-␣

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“…This association between TNF-α and heart failure severity led to the assessment of TNF as a potential target in heart failure. Small preliminary studies [5,6] provided encouraging safety and efficacy results of etanercept in lowering levels of biologically active TNF. There was a trend towards improvement in functional heart failure class as well.…”

Section: Introductionmentioning

confidence: 99%

Heart Failure with Etanercept Therapy: A Case Report

Ma¹,

Dorm²,

Neyses³

et al. 2013

J Clin Exp Cardiolog

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Tumour Necrosis Factor-alpha antagonists constitute an important part of the therapeutic armamentarium available for managing autoimmune diseases such as rheumatoid arthritis and psoriatic arthropathy. Here, we present the case of a 68-year old male with severe rheumatoid arthritis who developed chest pains and severe left ventricular systolic dysfunction following etanercept therapy. Etanercept was discontinued while he was commenced on standard heart failure treatment. This, consequently, led to complete resolution of his symptoms and recovery of left ventricular function to near normal. Previous literature involving similar case reports is reviewed and implications for clinical practice are discussed with emphasis on the need for a screening protocol when commencing such therapy.

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Results of Targeted Anti–Tumor Necrosis Factor Therapy With Etanercept (ENBREL) in Patients With Advanced Heart Failure

Abstract: Treatment with etanercept for 3 months was safe and well-tolerated in patients with advanced heart failure, and it resulted in a significant dose-dependent improvement in LV structure and function and a trend toward improvement in patient functional status.

Cited by 356 publications

References 7 publications

Inflammatory Biomarkers in Heart Failure

Inflammatory Biomarkers in Heart Failure

Myocardial Proinflammatory Cytokine Expression and Left Ventricular Remodeling in Patients With Chronic Mitral Regurgitation

Heart Failure with Etanercept Therapy: A Case Report

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