The role of inflammation and cell death in the pathogenesis, progression and treatment of heart failure
Chronic inflammation underlies a variety of seemingly unrelated conditions including coronary artery disease. The interest in exploring the role of inflammation in heart failure (CHF) arises from earlier observations that circulating pro inflammatory biomarker levels are elevated in patients with both ischaemic and non ischaemic cardiomyopathies and correlate with severity of disease and prognosis (McMurray et al. in Eur Heart J 33:1787 1847, 2012; Mosterd and Hoes in Heart 93:1137 1146, 2007; Owan et al. in New Engl J Med 355:251 259, 2006) In acute decompensated HF, pro inflammatory biomarker levels have been associated with mortality and readmission rates (Cowie et al. in Heart 83:505 510, 2000) Similar to neurohormonal activation and inflammation, production of pro inflammatory cytokines is a response to stress in an attempt to restore cellular function. However, sustained expression and exposure to cytokines can lead to left ventricular dysfunction, negative inotropic effects, altered cardiac metabolism, myocardial remodelling and HF progression. However, it is unclear whether elevated levels of pro inflammatory biomarkers, such as high sensitivity C reactive protein, signify an ongoing inflammatory process that leads to HF progression, or are merely markers of advanced disease. Beta blockers, renin angiotensin aldosterone axis antagonists, statins and immunosuppressants have been found to decrease the levels of cytokines in small clinical studies of patients with HF (Hobbs et al. in Heart J 28:1128 1134, 2007) However, 'immunomodulatory' approaches applied in the RECOVER, RENAISSANCE, ATTACH, IMAC and ACCLAIM double blind, placebo controlled studies had neutral or negative effects on outcomes of patients with HF. In the present review, we focus on the role of inflammation in pathogenesis and progression of the HF, the value of pro inflammatory cytokines as biomarkers and the potential therapeutic applications of immunomodulation in HF patients.
Heart Failure Reviews