Diabetes mellitus (DM) is a glucose metabolism disorder characterized by chronic hyperglycemia resulting from a deficit of insulin production and/or action. DM affects more than 1 in 10 adults, and it is associated with an increased risk of cardiovascular morbidity and mortality. Cardiovascular disease (CVD) accounts for two thirds of the overall deaths in diabetic patients, with coronary artery disease (CAD) and ischemic cardiomyopathy as the main contributors. Hyperglycemic damage on vascular endothelial cells leading to endothelial dysfunction represents the main initiating factor in the pathogenesis of diabetic vascular complications; however, the underlying pathophysiological mechanisms are still not entirely understood. This review addresses the current knowledge on the pathophysiological links between DM and CAD with a focus on the role of epigenetic modifications, including DNA methylation, histone modifications and noncoding RNA control. Increased knowledge of epigenetic mechanisms has contributed to the development of new pharmacological treatments (“epidrugs”) with epigenetic targets, although these approaches present several challenges. Specific epigenetic biomarkers may also be used to predict or detect the development and progression of diabetes complications. Further studies on diabetes and CAD epigenetics are needed in order to identify possible new therapeutic targets and advance personalized medicine with the prediction of individual drug responses and minimization of adverse effects.

There is evidence demonstrating that heart failure (HF) occurs in 1–2% of the global population and is often accompanied by comorbidities which contribute to increasing the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non-pharmacological approaches have led to a significant improvement in clinical outcomes in patients affected by HF, residual unmet needs remain, mostly related to the occurrence of poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to possibly contribute to protection of the failing myocardium, although their place in the treatment of HF requires further assessment, in order to find better therapeutic solutions. In this context, the Optimal Nutraceutical Supplementation in Heart Failure (ONUS-HF) working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease, in order to counteract selected pathways that are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring during the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, impaired cardiac stem cell mobilization and an imbalanced regulation of metalloproteinases. Moreover, we reviewed the potential of the nutraceutical supplementation of several natural products, such as coenzyme Q10 (CoQ10), a grape seed extract, Olea Europea L.-related antioxidants, a sodium–glucose cotransporter (SGLT2) inhibitor-rich apple extract and a bergamot polyphenolic fraction, in addition to their support in cardiomyocyte protection, in HF. Such an approach should contribute to optimising the use of nutraceuticals in HF, and the effect needs to be confirmed by means of more targeted clinical trials exploring the efficacy and safety of these compounds.

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome frequently seen in elderly patients, the incidence of which is steadily increasing due to an ageing population and the increasing incidence of diseases, such as diabetes, hypertension, obesity, chronic renal failure, and so on. It is a multifactorial disease with different phenotypic aspects that share left ventricular diastolic dysfunction, and is the cause of about 50% of hospitalizations for heart failure in the Western world. Due to the complexity of the disease, no specific therapies have been identified for a long time. Sodium-Glucose Co-Transporter 2 Inhibitors (SGLT2-Is) and Glucagon-Like Peptide Receptor Agonists (GLP-1 RAs) are antidiabetic drugs that have been shown to positively affect heart and kidney diseases. For SGLT2-Is, there are precise data on their potential benefits in heart failure with reduced ejection fraction (HFrEF) as well as in HFpEF; however, insufficient evidence is available for GLP-1 RAs. This review addresses the current knowledge on the cardiac effects and potential benefits of combined therapy with SGLT2-Is and GLP-1RAs in patients with HFpEF.

Atherosclerosis is a chronic inflammatory disease characterized by lipid and inflammatory cell deposits in the inner layer of large- and medium-sized elastic and muscular arteries. Diabetes mellitus (DM) significantly increases the risk of cardiovascular diseases and the overall and cardiovascular mortality, and it is a pro-atherogenic factor that induces atherosclerosis development and/or accelerates its progression through a multifactorial process. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of drugs, belonging to the armamentarium to fight type 2 DM, that have shown robust reductions in atherosclerotic events and all-cause mortality in all studies. Preclinical studies have shown that GLP-1RAs play a role in the immunomodulation of atherosclerosis, affecting multiple pathways involved in plaque development and progression. In this review, we wanted to explore the translational power of such preclinical studies by analyzing the most recent clinical trials investigating the atheroprotective effect of GLP-1RAs.

Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) is emerging as an effective treatment for patients with symptomatically failing bioprosthetic valves and a high prohibitive surgical risk; a longer life expectancy has led to a higher demand for these valve reinterventions due to the increased possibilities of outliving the bioprosthetic valve’s durability. Coronary obstruction is the most feared complication of valve-in-valve (ViV) TAVR; it is a rare but life-threatening complication and occurs most frequently at the left coronary artery ostium. Accurate pre-procedural planning, mainly based on cardiac computed tomography, is crucial to determining the feasibility of a ViV TAVR and to assessing the anticipated risk of a coronary obstruction and the eventual need for coronary protection measures. Intraprocedurally, the aortic root and a selective coronary angiography are useful for evaluating the anatomic relationship between the aortic valve and coronary ostia; transesophageal echocardiographic real-time monitoring of the coronary flow with a color Doppler and pulsed-wave Doppler is a valuable tool that allows for a determination of real-time coronary patency and the detection of asymptomatic coronary obstructions. Because of the risk of developing a delayed coronary obstruction, the close postprocedural monitoring of patients at a high risk of developing coronary obstructions is advisable. CT simulations of ViV TAVR, 3D printing models, and fusion imaging represent the future directions that may help provide a personalized lifetime strategy and tailored approach for each patient, potentially minimizing complications and improving outcomes.

This review describes the relationship between the coronavirus-related pandemic and health inequities. The latter are linked to pre-existing social and economic discriminations in terms of access to healthcare for people affected by chronic diseases. We believe that we are living in a “syndemic pandemic”. The term “syndemic” was originally developed by the medical anthropologist Merrill Singer in the 1990s in order to recognize the correlation between HIV/AIDS, illicit drug use, and violence in the United States. This complex interplay exacerbated the burden of the disease and the prognosis of the patient. Similarly, in COVID-19 infection, socio-economic, ethnic, and racial inequities result in higher morbidity and mortality in certain sections of society. Unfortunately, such differences are becoming too common during the COVID-19 pandemic, in terms of the incidence and prevalence of the disease, as well as inequal access to new medical advances and life-saving therapeutics for those with COVID-19, such as vaccines and monoclonal antibody treatment. Lockdown measures, imposed internationally as a response to the COVID-19 pandemic, are causing economic inequities, which complicate the issue even further. An appropriate syndemic anthropological approach is necessary to ensure that this pandemic does not increase health inequities in access to appropriate treatments.