Current Vascular Pharmacology - Current Issue

Emotional, mental, or psychological distress, defined as increased symptoms of depression, anxiety, and/or stress, is common in patients with chronic diseases, such as cardiovascular (CV) disease (CVD).

Literature was reviewed regarding data from studies and meta-analyses examining the impact of emotional stress on the occurrence and outcome of several CVDs (coronary disease, heart failure, hypertension, arrhythmias, stroke). These influences' pathophysiology and clinical spectrum are detailed, tabulated, and pictorially illustrated.

This type of stress is a newly recognized risk and prognosticator for CVD including coronary artery disease, heart failure, hypertension, cardiac arrhythmias, and stroke, independently of conventional risk factors. It can impact CV outcomes, and also affect health care utilization, with more patient visits to health care facilities. The biological systems activated by mental stress comprise the sympathetic nervous system (SNS), the renin-angiotensin system (RAS), and the hypothalamic-pituitary-adrenal (HPA) axis, while several other biological processes are disrupted, such as endothelial function, inflammatory responses, oxidative stress, mitochondrial function and the function of the amygdala which is the central nervous system processing center of emotions and emotional reactions.

Emotional stress that aggravates symptoms of depression, anxiety, and/or perceived mental stress is common in patients with chronic diseases, such as CVD. It is a newly recognized risk and prognosticator for several CVDs. It can influence CV outcomes, and also affect health care utilization. The biological systems activated by mental stress comprise the SNS, the RAS, and the HPA axis, while several other biological processes are disrupted.

Gut microbiota-derived metabolite Trimethylamine-N-oxide (TMAO) is increasingly recognized as a potential novel prognostic biomarker for cardiovascular disease. Our research work aimed to investigate the potential utility of TMAO measurement in patients with ST-elevation Myocardial Infarction (STEMI).

We performed a systematic literature search in PubMed from inception to the 1^st of February 2024 to identify all studies examining the association between plasma TMAO levels and disease complexity or clinical outcomes in STEMI patients.

A total of eight prospective cohort studies were included, encompassing a total of 2,378 STEMI patients. Three of the studies provided only in-hospital evidence (i.e., increased odds for more severe coronary artery disease, plaque rupture, and plaque healing in patients with increased TMAO levels). Four studies examined the long-term prognostic value of TMAO after 10-12 months of follow-up post-STEMI (i.e., increased risk of adverse cardiovascular events in patients with increased TMAO levels), while one study provided data for both in-hospital and mid-term prognosis, indicating that 4-months after STEMI patients with greater TMAO elevation had larger infarct size.

Higher TMAO levels were associated with a greater prevalence of high-risk coronary plaque characteristics and worse in-hospital and follow-up outcomes in STEMI patients. Further study is needed on whether modulating the diet-dependent TMAO levels could improve clinical outcomes in these patients.

[(OSF): https://doi.org/10.17605/OSF.IO/WNG8V].

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a groundbreaking class of antidiabetic medications renowned for their glucose-lowering effects and cardiovascular benefits. Recent studies have suggested that SGLT2 inhibitors may extend their influence beyond glycemic control to impact adipose tissue physiology, particularly within the epicardial adipose depot. Epicardial adipose tissue (EAT), an actively secretory organ surrounding the heart, has been implicated in the modulation of cardiovascular risk.

This systematic review and meta-analysis aims to systematically review and synthesize existing literature on the effects of SGLT2 inhibitors on EAT.

We performed a literature search for studies assessing the changes in epicardial adipose tissue volume/thickness before and after treatment with an SGLT2 inhibitor. We excluded reviews, editorials, case reports/case series, experimental studies, and studies that did not use SGLT2 inhibitors as the intervention. The main outcome of interest was the change in EAT volume/thickness at follow-up.

The literature search yielded 72 results. After the application of the exclusion criteria, a total of 11 studies were selected for data extraction and inclusion in the meta-analysis. A mean of 6.57ml decreased EAT volume, and EAT thickness was reduced by a mean of 1.55mm. We detected that treatment with an SGLT2 inhibitor was associated with decreased EAT volume/thickness compared to the control group (SMD -1.79, 95% CI -2.91 to -0.66, p<0.01). There was substantial between-study heterogeneity (I²: 94%, p<0.001). Results remained robust even after the exclusion of any single study. Subgroup analysis revealed a significantly greater effect size in randomized studies. Funnel plot inspection and Egger’s regression test did not indicate the presence of publication bias.

This meta-analysis suggests that SGLT2 inhibitors use is associated with a reduction in EAT volume/thickness, posing as a potential mechanism of their beneficial effects in heart failure (HF) outcomes.

The management of acute heart failure (AHF) is crucial and challenging. Regarding the use of inotropes, correct patient selection and time of administration are of the essence. We hypothesize that the early use of Levosimendan favouring hemodynamic stabilization and enables rapid optimization of guideline-directed medical therapy (GDMT) in patients with HF, eventually impacting the patient’s prognosis during the vulnerable phase.

This prospective, observational study enrolled consecutive patients admitted due to AHF. Propensity score matching (PSM) analysis has been used to homogenize differences between groups. In group 1 (G1), patients were treated with early 24-h Levosimendan infusion followed by in-hospital introduction/up-titration of GDMT. In group 2 (G2), patients were treated with alternative inotropes/vasopressors followed by in-hospital introduction/up-titration of GDMT. The comparison between the two groups has been performed at the 6-month follow-up in terms of cardiovascular (CV) mortality and HF hospitalizations (HFH).

233 patients were included in the present study, and after propensity match adjustments, 176 patients were analysed, 88 patients for each group. No differences in the baseline characteristics have been reported between the groups. At 6 months follow-up, no statistically significant differences were shown in terms of the composite endpoint of CV death and HFH (p = 0.445) and CV death (p = 0.62). Statistically significant differences between the two groups were reported in terms of HFH (p = 0.02). The Kaplan-Meier survival analysis showed that patients in G1 were significantly less hospitalized compared to G2 during the 6 months after the index hospitalization (log-rank p = 0.03).

Early 24-hour infusion of Levosimendan followed by rapid optimization of HF disease-modifying therapies results in a significant reduction of HFH in the vulnerable post-discharge phase.