Inflammation in Heart Failure: JACC State-of-the-Art Review

ongestive heart failure (CHF) is a complex clinicalsyndrome characterized by exercise intolerance, fati-gability, dyspnea, and volume retention occurring asa consequence of myocardial injury and subsequent dysfunc-tion. Progression of this disease is thought to be mediated byneurohormones, such as norepinephrine and angiotensin II,by virtue of the toxic effects that they exert on the heart andthe peripheral vasculature.

BNP in heart failure: even leucocytes cannot escape its influence.

Cardiac Autonomic Nerve Stimulation in the Treatment of Heart Failure

Heart failure

Resting cardiac power index and prediction of prognosis in heart failure.

Despite significant advances in the prevention and treatment of heart failure (HF), the prognosis in patients who have been hospitalised on at least one occasion due to exacerbation of HF is still poor. Therefore, a better understanding of the underlying pathophysiological mechanisms of HF is crucial in order to achieve better results in the treatment of this clinical syndrome. One of the areas that, for years, has aroused the interest of researchers is the activation of the immune system and the elevated levels of biomarkers of inflammation in patients with both ischaemic and non-ischaemic HF. Additionally, it is intriguing that the level of circulating pro-inflammatory biomarkers correlates with the severity of the disease and prognosis in this group of patients. Unfortunately, clinical trials aimed at assessing interventions to modulate the inflammatory response in HF have been disappointing, and the modulation of the inflammatory response has had either no effect or even a negative effect on the HF prognosis. The article presents a summary of current knowledge on the role of immune system activation and inflammation in the pathogenesis of HF. Understanding the immunological mechanisms pathogenetically associated with left ventricular remodelling and progression of HF may open up new therapeutic possibilities for HF.

See related article, pp 114–122 Immuno-inflammatory mechanisms have been implicated in the initiation and progression of heart failure (HF) during the past 2 decades. Despite several investigators having postulated a pathogenic role of inflammation in HF, clinical trials of anti-inflammatory and anti-immune therapies in HF have not resulted in salutary effects.1 Absence of a beneficial effect of these therapies has led to more questions than answers. Is the presence of inflammation really bad? Is inflammation good at 1 time point and detrimental at another? Are there subsets of inflammatory cells that have a protective role and others that are detrimental? Extensive research to answer these questions has led to the identification of unique subsets of the immune cascade that might have a selective protective role in HF. One such group of cells is the CD4+ regulatory T cells (Tregs). These cells are a part of the adaptive immune response of the body and are further divided into natural and adaptive Treg cells (Figure). Natural Tregs develop in the thymus against self-antigens, whereas adaptive Tregs develop in response to an antigenic stimulation. Adaptive Tregs express a specific transcription factor called FoxP3 and are often termed as CD4+CD25+Foxp3+T cells. Tregs have been shown to have atheroprotective properties.2 Dinh et al3 showed that selective expansion of Tregs by cytokine-based interleukin-2 (IL-2)/anti–IL-2 monoclonal antibody complex therapy can attenuate atherosclerosis in mice. Figure. Schematic description of the role of immune-inflammatory activation in the progression of heart failure. Regulatory T cells (Treg) with anti-inflammatory properties have been depicted. …

Section 13: Evaluation and Therapy for Heart Failure in the Setting of Ischemic Heart Disease

Heart failure (HF) is a leading cause of cardiovascular morbidity and mortality, with inflammation recognized as a key cause and byproduct. Despite observational studies linking elevated indices of inflammation with HF severity, as well as experimental models highlighting the centrality of inflammation to the pathogenesis of various types of HF, clinical trials of anti-inflammatory therapies in HF have produced inconsistent results. This variability may relate to the substrate included – differences in HF stage and/or clinical phenotype – as well as the mechanisms and target of therapeutics, whether aimed at preventing new-onset HF or treating established disease. This review evaluates clinical trials directly targeting inflammation in HF, with a focus on disease stage and symptomatology. Ultimately, by highlighting the importance of HF staging and the timing of therapeutics in prior inflammation-targeted interventions, we aim to inform more precise targets from a disease substrate perspective when designing trials of inflammation-modulating therapies in HF.

Managing atrial fibrillation in the CRT patient: Controversy or consensus?

Recent Trends in the Incidence, Treatment, and Prognosis of Patients With Heart Failure and Atrial Fibrillation (the Worcester Heart Failure Study)

Association Between Bilirubin and Mode of Death in Severe Systolic Heart Failure

Heart failure is a common condition responsible for at least 290 000 deaths each year in the United States alone.1 A small minority of heart failure cases are attributed to Mendelian or familial cardiomyopathies. The majority of systolic heart failure cases are not familial but represent the end result of 1 or many conditions that primarily injure the myocardium sufficiently to diminish cardiac output in the absence of compensatory mechanisms. Paradoxically, because they also injure the myocardium, it is the chronic actions of the compensatory mechanisms that in many instances contribute to the progression from simple cardiac injury to dilated cardiomyopathy and overt heart failure. Thus, the epidemiology of common heart failure appears to be just as sporadic as its major antecedent conditions (atherosclerosis, diabetes, hypertension, and viral myocarditis). Familial trends in preclinical cardiac remodeling2 and risk of developing heart failure3 reveal an important role for genetic modifiers in addition to clinical and environmental factors. Candidate gene studies performed over the past 10 years have identified a few polymorphic gene variants that modify risk or progression of common heart failure.4 Whole-genome sequencing will lead to the discovery of other genetic modifiers that were not candidates.5 The imminent availability of individual whole-genome sequences at a cost competitive with available genetic tests for familial cardiomyopathy will no doubt further expand the list of putative genetic heart failure modifiers. Heart failure risk alleles along with traditional clinical factors will need to be considered by clinical cardiologists in their design of optimal disease surveillance and prevention programs and in individually tailoring heart failure management. The use of individual genetic make-up is likely to have the earliest and greatest impact on managing patients with heart failure by tailoring available pharmacotherapeutics to optimize patient response and minimize adverse effects (ie, the …

Metabolic assessment of exercise in chronic heart failure patients treated with short-term vasodilators.

Heart failure (HF), a prevalent global health issue characterized by the heart's impaired ability to pump or fill blood, affects millions worldwide and continues to pose significant challenges despite advancements in treatment. This review delves into the critical and increasingly recognized role of inflammation in the development and progression of this complex syndrome. While the incidence of HF has seen a decline in some regions due to improved cardiac care, its overall prevalence is rising, particularly among younger adults and those with heart failure with a preserved ejection fraction (HFpEF). Given the persistently high rates of hospitalization and mortality associated with HF, understanding the underlying mechanisms, including the contribution of inflammation, is crucial for identifying novel therapeutic strategies. Inflammation in heart failure is a multifaceted process involving the activation of the immune system, both innate and adaptive, and encompasses various mechanisms such as the release of pro-inflammatory mediators, endothelial dysfunction, and neurohormonal activation. Myocardial damage triggers the innate immune response, while humoral immunity and chronic systemic inflammation, often linked to cardiovascular risk factors and autoimmune diseases, also play significant roles. Notably, heart failure and inflammation have a reciprocal relationship, with HF itself contributing to inflammatory processes within the cardiac tissue and systemically. Understanding these intricate pathways, including the involvement of specific immune cells and molecular mediators, is essential for comprehending the pathogenesis of heart failure and exploring potential therapeutic interventions. The review further examines various inflammatory biomarkers that have been implicated in heart failure, such as cytokines (including TNF-α and IL-1) and C-reactive protein (CRP). While these markers often correlate with the severity and prognosis of HF, clinical trials targeting specific inflammatory mediators have largely yielded disappointing results, highlighting the complexity of the inflammatory response in this context. The exploration of these biomarkers and the challenges encountered in translating anti-inflammatory strategies into effective treatments underscore the need for continued research to unravel the precise role of inflammation across different HF subtypes and to develop more targeted and effective anti-inflammatory therapies.