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.

A 57-year-old woman presented to the Emergency Department with symptoms of worsening heart failure (HF). She had a past medical history of breast cancer treated with surgery and chemotherapy with anthracyclines and no family history of cardiomyopathy (CMP). In the last year, she received a diagnosis of HF with normal coronary arteries, during hospitalization for acute onset of dyspnea and was treated with medical therapy. After several months, few days before admission to our hospital, an echocardiography (ECHO) showed features of left ventricular noncompaction (LVNC), not described in previous ECHO and further confirmed by cardiac magnetic resonance. This case highlights the current uncertainties regarding the pathogenesis of LVNC and the clinical challenge of cardiologists facing LVNC morphology to decide if they are observing a genetic CMP, a phenotype overlapping with dilated or hypertrophic CMP, or a variant of the left ventricular (LV) wall anatomy. No consensus exists among scientific communities regarding diagnostic criteria of LVNC and in most cases; the key element in the diagnostic decision is not the LVNC by itself, but the associated LV dilation and/or dysfunction, hypertrophy, arrhythmias, and embolic events.

Introduction: Heart failure (HF) affects approximately 2% of the population worldwide, remaining a major cause of hospitalization and mortality despite innovative therapeutic approaches introduced in the past few decades. Type 2 diabetes mellitus (T2D) contributes significantly to end-organ damage and HF-related complications and is associated with worse clinical status and increased all-cause and cardiovascular mortality in patients with HF with reduced (HFrEF) or with preserved ejection fraction (HFpEF), compared to HF patients without T2D. Recently, a novel class of antidiabetic drugs has been introduced: sodium glucose co-trasport-2 inhibitors (SGLT2i). Initially designed for patients with T2D to reduce kidney blood glucose resorption, SGLT2i rapidly gained attention among HF specialists since they were able to show a beneficial prognostic impact in patients affected by HF and T2D, even independently from the glycemic control as suggested by the EMPA-REG OUTCOME and CANVAS trials. Areas covered: The present review focuses on the mechanisms and the current clinical evidence supporting the use of SGLT2i in HF patients with T2D. Moreover, the SGLT2i pharmacokinetic and pharmacodynamic properties will be presented in order to better understand the rationale and the design of the ongoing clinical trials investigating directly the effect of this new class of drugs in patients with HF, even independently from T2D. Expert opinion: SGLT2i are emerging as an effective and safe therapy for the treatment of T2D and current evidence has unexpectedly demonstrated a robust cardiovascular protection in HF patients with T2D. Therefore, ongoing clinical trials are investigating directly the effect of this new class of drugs in patients with HF, even independently from T2D. However, it is methodologically disappointing that the mechanisms underlying the encouraging results in cardiovascular protection of this drug class are still not fully understood. A better understanding of the pharmacokinetic and pharmacodynamic properties of SGLT2i is necessary in order to better determine the effect of this new class of drugs in patients with HF.

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.

L’insufficienza cardiaca rappresenta l’epidemia cardiovascolare del XXI secolo, con prognosi ad oggi insoddisfacente e scarsa qualità della vita nonostante appropriate cure mediche. Negli ultimi due decenni solo due nuovi farmaci sono stati introdotti e ancor meno progressi sono stati fatti in merito ai dispositivi impiantabili. Infatti, il defibrillatore impiantabile rimane indicato per pazienti con frazione di eiezione ≤35% e la terapia di resincronizzazione cardiaca per quelli con QRS >130 ms ed evidenza di blocco di branca sinistra. Tuttavia, solo un terzo dei pazienti soddisfa tali criteri ed un’elevata percentuale di questi risulta poi non responder in termini di miglioramento dei sintomi. Proprio per pazienti con insufficienza cardiaca sintomatica, frazione di eiezione compresa tra 25% e 45% e QRS <130 ms, non candidabili a resincronizzazione cardiaca, la modulazione della contrattilità cardiaca rappresenta una concreta opzione terapeutica, essendosi rivelata sicura ed efficace nel ridurre i ricoveri per scompenso e nel migliorare i sintomi, la capacità funzionale e la qualità della vita.Obiettivo di questa rassegna è dunque riassumere i presupposti fisiopatologici, le attuali indicazioni e i recenti sviluppi in merito alle nuove applicazioni della modulazione della contrattilità cardiaca per pazienti con insufficienza cardiaca cronica.