Heart failure (HF) is a clinical syndrome due to heart dysfunction, but in which other organs are also involved, resulting in a complex multisystemic disease, burdened with high mortality and morbidity. This article focuses on the mutual relationship between the heart and liver in HF patients. Any cause of right heart failure can cause hepatic congestion, with important prognostic significance. We have analyzed the pathophysiology underlying this double interaction. Moreover, we have explored several biomarkers and non-invasive tests (i.e., liver stiffness measurement, LSM) potentially able to provide important support in the management of this complex disease. Cardiac biomarkers have been studied extensively in cardiology as a non-invasive diagnostic and monitoring tool for HF. However, their usefulness in assessing liver congestion in HF patients is still being researched. On the other hand, several prognostic scores based on liver biomarkers in patients with HF have been proposed in recent years, recognizing the important burden that liver involvement has in HF. We also discuss the usefulness of a liver stiffness measurement (LSM), which has been recently proposed as a reliable and non-invasive method for assessing liver congestion in HF patients, with therapeutic and prognostic intentions. Lastly, the relationship between LSM and biomarkers of liver congestion is not clearly defined; more research is necessary to establish the clinical value of biomarkers in assessing liver congestion in HF patients and their relationship with LSM.

Coronary microvascular dysfunction (CMD) plays a crucial role across the spectrum of heart failure (HF) pathology, contributing to disease development, progression, and outcomes. The pathophysiological mechanisms linking CMD to HF are complex and still not completely understood and include chronic inflammation, oxidative stress, and neurohormonal activation. Despite the diagnostic and prognostic relevance in patients with HF, there is no specific therapeutic strategy targeting CMD to date. Moreover, the diagnosis of this clinical condition is challenging. In this review article, we aim to discuss the different clinical pathogenetic mechanisms linking CMD to HF across the different spectra of these diseases, their prognostic relevance, and the possible therapeutic targets along with the remaining knowledge gaps in the field.

The aim of this article review is to analyze some models and clinical issues related to the implementation of accelerated diagnostic protocols based on specific cardiac biomarkers in patients admitted to the emergency department (ED) with symptoms compatible with acute cardiac disorders. Four specific clinical issues will be discussed in detail: (a) pathophysiological and clinical interpretations of circulating hs-cTnI and hs-cTnT levels; (b) the clinical relevance and estimation of the biological variation of biomarkers in patients admitted to the ED with acute and severe diseases; (c) the role and advantages of the point-of-care testing (POCT) methods for cardiac-specific biomarkers in pre-hospital and hospital clinical practice; and (d) the clinical role of specific cardiac biomarkers in patients with acute heart failure (AHF). In order to balance the risk between a hasty discharge versus the potential harms caused by a cardiac assessment in patients admitted to the ED with suspected acute cardiovascular disease, the measurement of specific cardiac biomarkers is essential for the early identification of the presence of myocardial dysfunction and/or injury and to significantly reduce the length and costs of hospitalization. Moreover, specific cardiac biomarkers (especially hs-cTnI and hs-cTnT) are useful predictors of mortality and major adverse cardiovascular events (MACE) in patients admitted to the ED with suspected acute cardiovascular disease. To guide the implementation of the most rapid algorithms for the diagnosis of Non-ST-Elevation Myocardial Infarction (NSTEMI) into routine clinical practice, clinical scientific societies and laboratory medicine societies should promote collaborative studies specifically designed for the evaluation of the analytical performance and, especially, the cost/benefit ratio resulting from the use of these clinical protocols and POCT methods in the ED clinical practice.

Heart failure (HF) is an increasingly prevalent disease with a major impact on morbidity and mortality worldwide. Continuous advancements in diagnostic and therapeutic strategies have significantly improved patient outcomes; however, precise biomarkers and novel therapeutic targets are still needed. In recent years, microRNAs (miRNAs) have emerged as promising biomarkers and potential therapeutic targets in HF. They consist of small, noncoding RNA molecules that regulate gene expression post-transcriptionally and are detectable in both tissues and blood, with disease-specific expression profiles that make them attractive candidates for non-invasive diagnosis, prognostic risk stratification, and even therapeutic interventions. In HF, miRNAs contribute to pathogenesis by modulating fibrosis, apoptosis, hypertrophy, and inflammation. The aim of this review is to analyze the role of circulating and tissue miRNAs in HF as biomarkers and as therapeutic targets. The future management of HF should include strategies to modulate miRNA expression in order to modify the disease trajectory and improve clinical outcomes.

Diagnostic and therapeutic advances in the cardiovascular field have caused a progressive reduction in mortality from acute causes, with an ever-increasing chronicity of cardiovascular pathologies. In recent years, mechanical supports have played a fundamental role, allowing the patient to be stabilized in the most critical phase of acute heart failure (AHF) and acting as a "bridge" for definitive therapies. Heart transplantation (HTx) is the gold-standard treatment for end-stage HF, but it is burdened by a series of critical issues that limit its use, first of all the shortage of grafts. It also requires the patient to take immunosuppressive therapy for life, which exposes him to a greater risk of infectious and oncological diseases. For these reasons, in the last years, mechanical supports are increasingly used as "destination therapy", alternatively to HTx. However, also mechanical supports are not free from critical issues that limit their use. In this review we aim to analyze critical issues and future perspectives of advanced HF therapies.

Sodium–glucose cotransporter 2 inhibitors (iSGLT2) have become the fourth pillar of the medical treatment for heart failure with reduced ejection fraction (HFrEF). However, the mechanisms of action of iSGLT2 remain poorly understood. The effectiveness of combined ARNI and iSGLT2 therapy in left ventricular (LV) remodeling is still under study. We aim to investigate the effects of ARNI + iSGLT2 combination therapy in patients affected by HFrEF in terms of ventricular remodeling using speckle tracking echocardiography (STE). In this observational study, 136 patients with HFrEF taking ARNI were enrolled. All patients were evaluated at baseline (before iSGLT2), at 3 months and at 12 months from the beginning of iSGLT2 therapy. Echocardiographic parameters, including STE analysis and volumetric and LV contractile function indices, were collected at the three timepoints. The objectives were (1) to evaluate the effects of ARNI + iSGLT2 combination therapy on ultrasound (US) measurements; (2) to evaluate the effects on the variation of laboratory data indicative of HF (NT-pro-BNP); and (3) to evaluate the medium-long term impact of the ARNI + iSGLT2 combination therapy in terms of major cardiovascular events (MACVE). After only three months of combined ARNI + iSGLT2 therapy, we reported a significant improvement in ventricular and atrial volumetric indices, systolic function indices and myocardial deformation parameters assessed by STE. We also reported a significant decrease in NTproBNP levels. This trend was confirmed at 12 months follow-up. Furthermore, narrowing down the analysis to patients who were already treated with ARNI when they started taking iSGLT2, we reported similar results in the improvement of US parameters and NTproBNP levels. Our study has shown that the ARNI + iSGLT2 combination therapy leads to a clinical improvement and positive ventricular remodeling. Even the single introduction of additional iSGLT-2 in HFrEF patients on an otherwise optimized therapy resulted in a significant improvement in US and laboratory variables. The results of our study suggest implementing iSGLT-2 therapy as soon as possible, as the structural and functional cardiac improvements achieved by these drugs are achieved in the short term and maintained in the long term.