Tirzepatide is a new molecule capable of controlling glucose blood levels by combining the dual agonism of Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) receptors. GIP and GLP1 are incretin hormones: they are released in the intestine in response to nutrient intake and stimulate pancreatic beta cell activity secreting insulin. GIP and GLP1 also have other metabolic functions. GLP1, in particular, reduces food intake and delays gastric emptying. Moreover, Tirzepatide has been shown to improve blood pressure and to reduce Low-Density Lipoprotein (LDL) cholesterol and triglycerides. Tirzepatide efficacy and safety were assessed in a phase III SURPASS 1–5 clinical trial program. Recently, the Food and Drug Administration approved Tirzepatide subcutaneous injections as monotherapy or combination therapy, with diet and physical exercise, to achieve better glycemic blood levels in patients with diabetes. Other clinical trials are currently underway to evaluate its use in other diseases. The scientific interest toward this novel, first-in-class medication is rapidly increasing. In this comprehensive and systematic review, we summarize the main results of the clinical trials investigating Tirzepatide and the currently available meta-analyses, emphasizing novel insights into its adoption in clinical practice for diabetes and its future potential applications in cardiovascular medicine.

Heart failure (HF) has a global prevalence of 1–2%, and the incidence around the world is growing. The prevalence increases with age, from around 1% for those aged 10% for those aged 70 years or over. Based on studies in hospitalized patients, about 50% of patients have heart failure with reduced ejection fraction (HFrEF), and 50% have heart failure with preserved ejection fraction (HFpEF). HF is associated with high morbidity and mortality, and HF-related hospitalizations are common, costly, and impact both quality of life and prognosis. More than 5–10% of patients deteriorate into advanced HF (AdHF) with worse outcomes, up to cardiogenic shock (CS) condition. Right heart catheterization (RHC) is essential to assess hemodynamics in the diagnosis and care of patients with HF. The aim of this article is to review the evidence on RHC in various clinical scenarios of patients with HF.

Acute heart failure (AHF) is a complex clinical syndrome characterized by the rapid or gradual onset of symptoms and/or signs of heart failure (HF), leading to an unplanned hospital admission or an emergency department visit. AHF is the leading cause of hospitalization in patients over 65 years, thus significantly impacting public health care. However, its prognosis remains poor with high rates of mortality and rehospitalization. Many pre-existing cardiac conditions can lead to AHF, but it can also arise de novo due to acute events. Therefore, understanding AHF etiology could improve patient management and outcomes. Cardiomyopathies (CMPs) are a heterogeneous group of heart muscle diseases, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), non-dilated cardiomyopathy (NDLVC), and arrhythmogenic right ventricular cardiomyopathy (ARVC), that frequently present with HF. Patients with CMPs are under-represented in AHF studies compared to other etiologies, and therefore therapeutic responses and prognoses remain unknown. In DCM, AHF represents the most frequent cause of death despite treatment improvements. Additionally, DCM is the first indication for heart transplant (HT) among young and middle-aged adults. In HCM, the progression to AHF is rare and more frequent in patients with concomitant severe left ventricle (LV) obstruction and hypertrophy or severe LV systolic dysfunction. HF is the natural evolution of patients with RCM and HF is associated with poor outcomes irrespective of RCM etiology. Furthermore, while the occurrence of AHF is rare among patients with ARVC, this condition in NDLVC patients is currently unknown. In this manuscript, we assessed the available evidence on AHF in patients with CMPs. Data on clinical presentation, therapeutic management, and clinical outcomes according to specific CMPs are limited. Future HF studies assessing the clinical presentation, treatment, and prognosis of specific CMPs are warranted.

In the past decades, percutaneous coronary intervention (PCI) has become the most common modality for myocardial revascularization in patients with coronary artery disease (CAD). Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is essential in all patients undergoing PCI to prevent thrombotic complications. A large proportion of patients undergoing PCI also have concomitant atrial fibrillation (AF), thus requiring an oral anticoagulant (OAC) to prevent ischemic stroke or systemic embolism. However, the association between OAC and DAPT further increases the risk of bleeding. Compared with a triple antithrombotic therapy (TAT), dual antithrombotic therapy (DAT) has shown to reduce bleeding events, but at the cost of higher risk of stent thrombosis. In this field, patients with AF undergoing PCI represent a special population with significant challenges, and several strategies are needed to reduce the risk for bleeding complications. In this review, we will discuss both the procedural and antithrombotic strategies to optimize ischemic and bleeding outcomes in patients with AF undergoing PCI.

Cardiovascular diseases (CVDs), including coronary artery disease (CAD), are the main causes of mortality and morbidity worldwide. The pathophysiology of CAD includes atherosclerosis, a chronic process leading to atherosclerotic plaque development. Clinical manifestations could be chronic, such as in the chronic coronary syndrome (CCS) scenario, or acute, such as acute coronary syndrome (ACS). The risk of subsequent cardiovascular (CV) events depends on the risk category defined by international guidelines. In particular, patients who have experienced a CV event requiring percutaneous coronary intervention (PCI) remain at heightened residual risk for subsequent events, despite advancements in standard-of-care strategies. Therefore, comprehensive residual risk management is essential in this population to mitigate ischemic risk. Secondary prevention includes different targets of treatments—hypertension, dyslipidemia, diabetes mellitus, body weight control, smoking habit reduction, and healthy lifestyle promotion. Nevertheless, there is a critical, unmet need for therapeutic strategies for this high-risk population. Growing evidence shows that atherogenic lipids and vascular inflammation drive residual risk after PCI, despite guideline-directed therapy. This review summarizes more recent evidence about secondary prevention focusing on optimal medical therapy (OMT), targeting lipids and inflammation for patients undergoing PCI.

Current therapeutic strategies for acute heart failure (AHF) are based on traditional inotropic agents that are often associated with untoward effects; therefore, finding new effective approaches with a safer profile is dramatically needed. Istaroxime is a novel compound, chemically unrelated to cardiac glycosides, that is currently being studied for the treatment of AHF. Its effects are essentially related to its inotropic and lusitropic positive properties exerted through a dual mechanism of action: activation of the sarcoplasmic reticulum Ca²⁺ ATPase isoform 2a (SERCA2a) and inhibition of the Na⁺/K⁺-ATPase (NKA) activity. The advantages of istaroxime over the available inotropic agents include its lower arrhythmogenic action combined with its capability of increasing systolic blood pressure without augmenting heart rate. However, it has a limited half-life (1 hour) and is associated with adverse effects including pain at the injection site and gastrointestinal issues. Herein, we describe the main mechanism of action of istaroxime and we present a systematic overview of both clinical and preclinical trials testing this drug, underlining the latest insights regarding its adoption in clinical practice for AHF.