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Purpose of Review With the intention to summarize the currently available evidence on the pathophysiological relevance of inflammation in heart failure, this review addresses the question whether inflammation is a cause or consequence of heart failure, or both. Recent Findings This review discusses the diversity (sterile, para-inflammation, chronic inflammation) and sources of inflammation and gives an overview of how inflammation (local versus systemic) can trigger heart failure. On the other hand, the review is outlined how heart failure-associated wall stress and signals released by stressed, malfunctioning, or dead cells (DAMPs: e.g., mitochondrial DNA, ATP, S100A8, matricellular proteins) induce cardiac sterile inflammation and how heart failure provokes inflammation in various peripheral tissues in a direct (inflammatory) and indirect (hemodynamic) manner. The crosstalk between the heart and peripheral organs (bone marrow, spleen, gut, adipose tissue) is outlined and the importance of neurohormonal mechanisms including the renin angiotensin aldosteron system and the ß-adrenergic nervous system in inflammation and heart failure is discussed. Summary Inflammation and heart failure are strongly interconnected and mutually reinforce each other. This indicates the difficulty to counteract inflammation and heart failure once this chronic vicious circle has started and points out the need to control the inflammatory process at an early stage avoiding chronic inflammation and heart failure. The diversity of inflammation further addresses the need for a tailored characterization of inflammation enabling differentiation of inflammation and subsequent target-specific strategies. It is expected that the characterization of the systemic and/or cardiac immune profile will be part of precision medicine in the future of cardiology.

Purpose of Review In this review, we highlight the most important cellular and molecular mechanisms that contribute to cardiac inflammation and fibrosis. We also discuss the interplay between inflammation and fibrosis in various precursors of heart failure (HF) and how such mechanisms can contribute to myocardial tissue remodelling and development of HF. Recent Findings Recently, many research articles attempt to elucidate different aspects of the interplay between inflammation and fibrosis. Cardiac inflammation and fibrosis are major pathophysiological mechanisms operating in the failing heart, regardless of HF aetiology. Currently, novel therapeutic options are available or are being developed to treat HF and these are discussed in this review. Summary A progressive disease needs an aggressive management; however, existing therapies against HF are insufficient. There is a dynamic interplay between inflammation and fibrosis in various precursors of HF such as myocardial infarction (MI), myocarditis and hypertension, and also in HF itself. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the inflammatory and fibrotic pathways are essential, and specific drugs that target these pathways need to be evaluated.

Purpose of Review (Mal-)nutrition of micronutrients, like selenium, has great impact on the human heart and improper micronutrient intake was observed in 30–50% of patients with heart failure. Low selenium levels have been reported in Europe and Asia and thought to be causal for Keshan disease. Selenium is an essential micronutrient that is needed for enzymatic activity of the 25 so-called selenoproteins, which have a broad range of activities. In this review, we aim to summarize the current evidence about selenium in heart failure and to provide insights about the potential mechanisms that can be modulated by selenoproteins. Recent Findings Suboptimal selenium levels (<100 μg/L) are prevalent in more than 70% of patients with heart failure and were associated with lower exercise capacity, lower quality of life, and worse prognosis. Small clinical trials assessing selenium supplementation in patients with HF showed improvement of clinical symptoms (NYHA class), left ventricular ejection fraction, and lipid profile, while governmental interventional programs in endemic areas have significantly decreased the incidence of Keshan disease. In addition, several selenoproteins are found impaired in suboptimal selenium conditions, potentially aggravating underlying mechanisms like oxidative stress, inflammation, and thyroid hormone insufficiency. Summary While the current evidence is not sufficient to advocate selenium supplementation in patients with heart failure, there is a clear need for high level evidence to show whether treatment with selenium has a place in the contemporary treatment of patients with HF to improve meaningful clinical endpoints. Graphical abstract Graphical summary summarizing the potential beneficial effects of the various selenoproteins, locally in cardiac tissues and systemically in the rest of the body. In short, several selenoproteins contribute in protecting the integrity of the mitochondria. By doing so, they contribute indirectly to reducing the oxidative stress as well as improving the functionality of immune cells, which are in particular vulnerable to oxidative stress. Several other selenoproteins are directly involved in antioxidative pathways, next to excreting anti-inflammatory effects. Similarly, some selenoproteins are located in the endoplasmic reticulum, playing roles in protein folding. With exception of the protection of the mitochondria and the reduction of oxidative stress, other effects are not yet investigated in cardiac tissues. The systemic effects of selenoproteins might not be limited to these mechanisms, but also may include modulation of endothelial function, protection skeletal muscles, in addition to thyroid metabolism. Abbreviations: DIO, iodothyronine deiodinase; GPx, glutathione peroxidase; MsrB2, methionine-R-sulfoxide reductase B2; SELENOK, selenoprotein K; SELENON, selenoprotein N; SELENOP, selenoprotein P; SELENOS, selenoprotein S; SELENOT, selenoprotein T; TXNRD, thioredoxin reductase.

Purpose of Review Depression, anxiety, and cognitive impairment constitute established risk markers for incident cardiovascular disease (CVD) and are associated with impaired life expectancy and quality of life and high hospitalization rates and healthcare expenditure. This review summarizes current knowledge about mental health disorders in patients with CVD and heart failure (HF). Recent Findings Emerging evidence suggests various shared pathophysiological mechanisms between psychological comorbidities and CVD (e.g., systemic inflammation and autonomic dysfunction). Bi-directional interactions involving the central nervous and cardiovascular systems may help explain the rising prevalence of comorbid mood disorders with increasing CVD severity and support the concept of alternative pathophysiological mechanisms in the presence of severe somatic illness, making symptoms less responsive or unresponsive to psychotropic pharmacotherapy. Summary Considering high prevalence and negative impact of psychological comorbidities in CVD and HF, routine care should integrate screening for these conditions. Multidisciplinary treatment approaches with active patient participation in disease management were shown to improve outcomes. However, better understanding of factors mediating the adverse prognostic effects of mood disorders is needed. This might enable more targeted treatment and possibly also facilitate better understanding of the pathophysiological mechanisms driving CVD.

Purpose of Review This review discusses the mechanisms, clinical implications, and treatments of left atrial (LA) myopathy in comorbid atrial fibrillation (AF) and heart failure (HF) across the spectrum of ejection fraction. Recent Findings AF and HF are highly comorbid conditions. Left atrial (LA) myopathy, characterized by impairments in LA structure, function, or electrical conduction, plays a fundamental role in the development of both AF and HF with preserved ejection fraction (AF-HFpEF) along with AF and HF with reduced ejection fraction (AF-HFrEF). While the nature of LA myopathy in AF-HFpEF is unique from that of AF-HFrEF, LA myopathy also leads to progression of both of these conditions. Summary There may be a vulnerable cohort of AF-HF patients who have a disproportionate degree of LA myopathy compared with left ventricular (LV) dysfunction. Further investigations are required to identify therapies to improve LA function in this cohort.

Purpose of Review Heart failure (HF) is a structural or functional cardiac abnormality which leads to failure of the heart to deliver oxygen commensurately with the requirements of the tissues and it may progress to a generalized wasting of skeletal muscle, fat tissue, and bone tissue (cardiac cachexia). Clinically, dyspnea, fatigue, and exercise intolerance are some typical signs and symptoms that characterize HF patients. This review focused on the phenotypic characteristics of HF-induced skeletal myopathy as well as the mechanisms of muscle wasting due to HF and highlighted possible therapeutic strategies for skeletal muscle wasting in HF. Recent Findings The impaired exercise capacity of those patients is not attributed to the reduced blood flow in the exercising muscles, but rather to abnormal metabolic responses, myocyte apoptosis and atrophy of skeletal muscle. Specifically, the development of skeletal muscle wasting in chronic HF is characterized by structural, metabolic, and functional abnormalities in skeletal muscle and may be a result not only of reduced physical activity, but also of metabolic or hormonal derangements that favour catabolism over anabolism. In particular, abnormal energy metabolism, mitochondrial dysfunction, transition of myofibers from type I to type II, muscle atrophy, and reduction in muscular strength are included in skeletal muscle abnormalities which play a central role in the decreased exercise capacity of HF patients. Summary Skeletal muscle alterations and exercise intolerance observed in HF are reversible by exercise training, since it is the only demonstrated intervention able to improve skeletal muscle metabolism, growth factor activity, and functional capacity and to reverse peripheral abnormalities.

Purpose of Review Chronic obstructive pulmonary disease (COPD) is common in heart failure (HF), and it has a significant impact on the prognosis and quality of life of patients. Additionally, COPD is independently associated with lower adherence to first-line HF therapies. In this review, we outline the challenges of identifying and managing HF with preserved (HFpEF) and reduced (HFrEF) ejection fraction with coexisting COPD. Recent Findings Spirometry is necessary for COPD diagnosis and prognosis but is underused in HF. Therefore, misdiagnosis is a concern. Also, disease-modifying drugs for HF and COPD are usually safe but underprescribed when HF and COPD coexist. Summary Patients with HF-COPD are poorly enrolled in clinical trials. Guidelines recommend that HF treatment should be offered regardless of COPD presence, but modern registries show that undertreatment persists. Treatment gaps could be attenuated by ensuring an accurate and earlier COPD diagnosis in patients with HF, clarifying the concerns related to pharmacotherapy safety, and increasing the use of non-pharmacologic treatments. Acknowledging the uncertainties, this review aims to provide key clinical resources to support better physician-patient co-decision-making and improve collaboration between health professionals.

Purpose of the review Coronavirus Disease 2019 (COVID-19) and cardiovascular (CV) disease have a close relationship that emerged from the earliest reports. The aim of this review is to show the possible associations between COVID-19 and heart failure (HF) with preserved ejection fraction (HFpEF). Recent findings In hospitalized patients with COVID-19, the prevalence of HFpEF is high, ranging from 4 to 16%, probably due to the shared cardio-metabolic risk profile. Indeed, comorbidities including hypertension, diabetes, obesity and chronic kidney disease — known predictors of a severe course of COVID-19 — are major causes of HFpEF, too. COVID-19 may represent a precipitating factor leading to acute decompensation of HF in patients with known HFpEF and in those with subclinical diastolic dysfunction, which becomes overt. COVID-19 may also directly or indirectly affect the heart. In otherwise healthy patients, echocardiographic studies showed that the majority of COVID-19 patients present diastolic (rather than systolic) impairment, pulmonary hypertension and right ventricular dysfunction. Such abnormalities are observed both in the acute or subacute phase of COVID-19. Cardiac magnetic resonance reveals myocardial inflammation and fibrosis in up to the 78% of patients in the chronic phase of the disease. Summary These findings suggest that COVID-19 might be a novel independent risk factor for the development of HFpEF, through the activation of a systemic pro-inflammatory state. Follow-up studies are urgently needed to better understand long-term sequelae of COVID-19 inflammatory cardiomyopathy.

Purpose of Review Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent among individuals with obesity, primarily due to metabolic dysfunction and structural cardiac remodeling. This review explores the emerging therapeutic role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in managing HFpEF in obese populations. Recent Findings Recent clinical trials, including the STEP-HFpEF and SUMMIT studies, have shown that GLP-1 RAs such as semaglutide and tirzepatide significantly reduce body weight (13.3% and 13.9%, respectively), enhance exercise capacity (increases of 21.5m and 26m in 6-minute walk distance), and improve quality of life (19.5 and 16.6-point increases in KCCQ-CSS scores). Additionally, both agents demonstrated marked reductions in systemic inflammation, with C-reactive protein levels decreasing by 38.8% and 43.5%, respectively. Summary GLP-1 RAs represent a promising class of agents targeting the cardiometabolic axis in HFpEF, offering meaningful improvements in functional capacity and symptom burden among obese patients. However, current evidence is limited by short trial durations, lack of population diversity, and insufficient long-term data. Future research should focus on more inclusive cohorts and extended outcomes such as hospitalization rates and cardiovascular events to fully define the long-term safety and efficacy of GLP-1 RAs in HFpEF management.

Purpose Amyloidosis represents an increasingly recognized but still frequently missed cause of heart failure. In the light of many effective therapies for light chain (AL) amyloidosis and promising new treatment options for transthyretin (ATTR) amyloidosis, awareness among caregivers needs to be raised to screen for amyloidosis as an important and potentially treatable differential diagnosis. This review outlines the diversity of cardiac amyloidosis, its relation to heart failure, the diagnostic algorithm, and therapeutic considerations that should be applied depending on the underlying type of amyloidosis. Recent Findings Non-biopsy diagnosis is feasible in ATTR amyloidosis in the absence of a monoclonal component resulting in higher detection rates of cardiac ATTR amyloidosis. Biomarker-guided staging systems have been updated to facilitate risk stratification according to currently available biomarkers independent of regional differences, but have not yet prospectively been tested. Novel therapies for hereditary and wild-type ATTR amyloidosis are increasingly available. The complex treatment options for AL amyloidosis are improving continuously, resulting in better survival and quality of life. Mortality in advanced cardiac amyloidosis remains high, underlining the importance of early diagnosis and treatment initiation. Summary Cardiac amyloidosis is characterized by etiologic and clinical heterogeneity resulting in a frequently delayed diagnosis and an inappropriately high mortality risk. New treatment options for this hitherto partially untreatable condition have become and will become available, but raise challenges regarding their implementation. Referral to specialized centers providing access to extensive and targeted diagnostic investigations and treatment initiation may help to face these challenges.