Effects of sodium–glucose cotransporter-2 inhibitors on cardiac structural and electrical remodeling: from myocardial cytology to cardiodiabetology

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have changed the clinical landscape of diabetes mellitus (DM) therapy through their favourable effects on cardiovascular outcomes. Notably, the use of SGLT2i has been linked to cardiovascular benefits regardless of DM status, while their pleiotropic actions remain to be fully elucidated. What we do know is that SGLT2i exert beneficial effects even at the level of the myocardial cell, and that these are linked to an improvement in the energy substrate, resulting in less inflammation and fibrosis. SGLT2i ameliorate myocardial extracellular matrix remodeling, cardiomyocyte stiffness and concentric hypertrophy, achieving beneficial remodeling of the left ventricle with significant implications for the pathogenesis and outcome of heart failure. Most studies show a significant improvement in markers of diastolic dysfunction along with a reduction in left ventricular hypertrophy. In addition to these effects there is electrophysiological remodeling, which explains initial data suggesting that SGLT2i have an antiarrhythmic action against both atrial and ventricular arrhythmias. However, future studies need to clarify not only the exact mechanisms of this beneficial functional, structural, and electrophysiological cardiac remodeling, but also its magnitude, and to determine whether this is a class or a drug effect.

Interleukin-10 in the Vasculature: Pathophysiological Implications

Interleukin-10 (IL-10) is an important immunomodulatory cytokine, initially characterized as an anti-inflammatory agent released by immune cells during infectious and inflammatory processes. IL-10 exhibits biological functions that extend to the regulation of different intracellular signaling pathways directly associated with vascular function. This cytokine plays a vital role in vascular tone regulation through the change of important proteins involved in vasoconstriction and vasodilation. Numerous investigations covered here have shown that therapeutic strategies inducing IL-10 result in anti-inflammatory, anti-hypertrophic, antihyperplastic, anti-apoptotic and antihypertensive effects. This non-systematic review summarizes the modulating effects mediated by IL-10 in vascular tissue, particularly on vascular tone, and the intracellular pathway induced by this cytokine. We also highlight the advances in IL-10 manipulation as a therapeutic target in different cardiovascular pathophysiologies, including the physiological implications in animals and humans. Finally, the review illustrates current and potential future perspectives of the potential use of IL-10 in clinical trials, based on the clinical evidence.

The fundamental role of stress echo in evaluating coronary artery disease in specific patient populations

: Stress echocardiography (SE) was initially used for assessing patients with known or suspected coronary heart disease by detecting and evaluating myocardial ischemia and viability. The implementation of SE has gradually been extended to several cardiovascular diseases beyond coronary artery disease, and SE protocols have been modified and adapted for the detection of coronary artery disease (CAD) or other cardiovascular diseases in specific patient populations. This review attempts to summarize current data concerning SE implementation and clinical value in these specific and diverse populations: patients with an intramural course of a coronary artery – known as a myocardial bridge, chronic severe or end-stage hepatic disease, chronic severe or end-stage kidney disease, cardiac allograft vasculopathy, patients scheduled for solid-organ transplantation and other intermediate and high-risk surgery and, finally, patients treated with anticancer drugs or radiotherapy.

Narrative review of recent studies on the role of vitamin D in the prevention of cardiac and renal risk and additional considerations for COVID-19 vulnerability

: The role of vitamin D in maintaining a healthy cardiovascular (CV) and the renal system has received increasing attention. Low vitamin D levels are associated with the incidence of hypertension, cardiac remodeling, and chronic congestive heart failure. Low vitamin D levels also influence renal disease progression and albuminuria deterioration. Moreover, recent research indicates that vitamin D deficiency can be a potential risk factor for coronavirus disease-19 (COVID-19) infection and poorer outcomes. Data are inconclusive as to whether supplementation with vitamin D agents reduces CV disease risk or COVID-19 severity. Conversely, in patients with kidney disease, vitamin D supplementation is associated with improved kidney function and albuminuria. This narrative review considers recent data on the effects of vitamin D on the CV and renal system, as well as its possible role regarding COVID-19 complications.

Management of Dyslipidaemia for the Prevention of Stroke: Clinical Practice Recommendations from the Lipid Association of India

Stroke is the second most common cause of death worldwide. The rates of stroke are increasing in less affluent countries predominantly because of a high prevalence of modifiable risk factors. The Lipid Association of India (LAI) has provided a risk stratification algorithm for patients with ischaemic stroke and recommended low density lipoprotein cholesterol (LDL-C) goals for those in a very high risk group and extreme risk group (category A) of <50 mg/dl (1.3 mmol/l) while the LDL-C goal for extreme risk group (category B) is ≤30 mg/dl (0.8 mmol/l). High intensity statins are the first-line lipid lowering therapy. Non-statin therapy like ezetimibe and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors may be added as an adjunct to statins in patients who do not achieve LDL-C goals statins alone. In acute ischaemic stroke, high intensity statin therapy improves neurological and functional outcomes regardless of thrombolytic therapy. Although conflicting data exist regarding increased risk of intracerebral haemorrhage (ICH) with statin use, the overall benefit risk ratio favors long-term statin therapy necessitating detailed discussion with the patient. Patients who have statins withdrawn while being on prior statin therapy at the time of acute ischaemic stroke have worse functional outcomes and increased mortality. LAI recommends that statins be continued in such patients. In patients presenting with ICH, statins should not be started in the acute phase but should be continued in patients who are already taking statins. ICH patients, once stable, need risk stratification for atherosclerotic cardiovascular disease (ASCVD).

Epicardial adipocyte-derived TNF-α modulates local inflammation in patients with advanced coronary artery disease

Background: Epicardial adipose tissue (EAT) surrounds the epicardium and can mediate harmful effects related to coronary artery disease (CAD). Objective: We explored the regional differences between adipose stores surrounding diseased and non-diseased segments of coronary arteries in patients with advanced CAD. Methods: We enrolled 32 patients with known CAD who underwent coronary artery bypass graft (CABG) surgery. Inflammatory mediators were measured in EAT biopsies collected from a region of the left anterior descending artery (LAD) with severe stenosis (diseased segment) and without stenosis (non-diseased segment). Results : Mean age was 64.3±11.1 years, and mean EAT thickness was 7.4±1.9 mm. Dyslipidemia was the most prevalent comorbidity (81% of the patients). Out of a total of 11 cytokines, resistin (p=0.039), matrix metallopeptidase 9 (MMP-9) (p=0.020), C-C motif chemokine ligand 5 (CCL-5) (p=0.021), and follistatin (p=0.038) were significantly increased in the diseased compared with the non-diseased EAT segments. Indexed tumor necrosis factor-alpha (TNF-α), defined as the diseased to non-diseased cytokine levels ratio, was significantly correlated with increased EAT thickness both in the whole cohort (p=0.043) and in a subpopulation of patients with dyslipidemia (p=0.009). Treatment with lipid-lowering agents significantly decreased indexed TNF-α levels (p=0.015). No significant alterations were observed in the circulating levels of these cytokines with respect to CAD-associated comorbidities. Conclusion: Perivascular EAT is a source of cytokine secretion in distinct areas surrounding the coronary arteries in patients with advanced CAD. Adipocyte-derived TNF-α is a prominent mediator of local inflammation.