Coronary microvascular dysfunction (CMD) is related to a broad variety of clinical scenarios in which cardiac microvasculature is morphologically and functionally affected, and it is associated with impaired responses to vasoactive stimuli. Although the prevalence of CMD involves about half of all patients with chronic coronary syndromes and more than 20% of those with acute coronary syndrome, the diagnosis of CMD is often missed, leading to the underestimation of its clinical importance. The established and validated techniques for the measurement of coronary microvascular function are invasive and expensive. An ideal method to assess endothelial dysfunction should be accurate, non-invasive, cost-effective and accessible. There are varieties of biomarkers available, potentially involved in microvascular disease, but none have been extensively validated in this heterogeneous clinical population. The investigation of potential biomarkers linked to microvascular dysfunction might improve the assessment of the diagnosis, risk stratification, disease progression and therapy response. This review article offers an update about traditional and novel potential biomarkers linked to CMD.

Background/Objectives: Anemia and renal impairment are key predictors of adverse outcomes in acute coronary syndromes (ACSs). The hemoglobin-to-creatinine (Hb/Cr) ratio combines these parameters into a simple index. This study aimed to evaluate its prognostic value at discharge in patients with ST-elevation myocardial infarction (STEMI). Methods: The primary endpoint was one-year all-cause mortality; secondary endpoints included major bleeding and the composite of all-cause mortality or reinfarction. Optimal Hb/Cr cut-off values were identified using Liu’s method. Multivariable logistic regression and propensity score matching were used to assess associations with outcomes. Results: We analyzed 11,236 STEMI patients from the PRAISE registry with available hemoglobin and creatinine values at discharge. The optimal cut-points were 13.68 for mortality and 14.42 for secondary endpoints. Patients were stratified into low (<13.68; 26.5%) and high (≥13.68; 73.5%) Hb/Cr groups. The low Hb/Cr group was older, had more comorbidities, and received less intensive therapy. At one year, low Hb/Cr patients had significantly higher rates of all-cause mortality (8.7% vs. 2.4%), major bleeding (5.0% vs. 2.4%), and the composite outcome (11.5% vs. 4.9%). In the multivariate logistic regression, the Hb/Cr ratio was inversely associated with all outcomes, namely all-cause mortality (odds ratio [OR] 0.94; 95% confidence interval [CI]: 0.92–0.96), major bleeding (OR 0.96; 95% CI: 0.94–0.97), and the composite endpoint (OR 0.93; 95% CI: 0.91–0.96). The Hb/Cr ratio outperformed hemoglobin and creatinine alone in predicting mortality (AUC 0.684 vs. 0.649 and 0.645; p < 0.001). Conclusions: The Hb/Cr ratio is independently associated with one-year adverse outcomes in STEMI and may serve as a simple marker of increased vulnerability. Prospective studies are needed to validate its clinical utility.

According to available evidence, sodium-glucose cotransporter-2 inhibitors (SGLT2i) may confer cardioprotection in patients with cancer undergoing chemotherapy. The objective of the study was to evaluate the impact of SGLT2i on all-cause mortality and heart failure (HF) outcomes in this population. We searched PubMed, Cochrane CENTRAL, and Embase through August 2025 for studies of SGLT2i in adult patients with cancer. Random-effects models were used to pool effects for all-cause mortality and an HF composite (new-onset HF and/or HF hospitalization) in cancer patients >18 years. Meta-regression tested effect modification by beta-blockers, statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, age, and sex. Thirteen observational studies were included, for a total of 107,126 patients. The median age was 67.6 years (IQR: 62.5-71.0); median follow-up was 24 months (IQR: 19.2-29.0), nearly all patients had diabetes mellitus. SGLT2i were associated with lower all-cause mortality (risk ratio [RR]: 0.47; 95% CI: 0.38-0.58; I² = 96.30%; P < 0.001), with no effect modification by background therapies, age, or sex (all P > 0.05). The HF composite was also significantly reduced (RR: 0.48; 95% CI: 0.29-0.78; I² = 87.01%), again with no evidence that background therapies modified the effect (all P > 0.05). Risk of atrial fibrillation/atrial flutter was lower with SGLT2i (RR: 0.57; 95% CI: 0.42-0.76; I² = 66.4%; P < 0.001). Safety outcomes were not increased in the SGLT2i arm. In patients with cancer, SGLT2i appear safe and are associated with fewer deaths and HF events, although substantial heterogeneity was observed across studies. Randomized controlled trials are warranted to confirm these hypothesis-generating findings.

Permanent pacemaker implantation (PPI) represents a frequent complication after transcatheter aortic valve implantation (TAVI) due to atrio-ventricular (AV) node injury. Predictors of early AV function recovery were investigated. We analyzed 50 consecutive patients (82 ± 6 years, 58% males, EuroSCORE: 7.8 ± 3.3%, STS mortality score: 5 ± 2.8%). Pacemaker interrogations within 4–6 weeks from PPI were performed to collect data on AV conduction. The most common indication of PPI was persistent third-degree (44%)/high-degree (20%) AV block/atrial fibrillation (AF) with slow ventricular conduction (16%) after TAVI. At follow-up, 13 patients (26%) recovered AV conduction (i.e., sinus rhythm with stable 1:1 AV conduction/AF with a mean ventricular response >50 bpm, associated with a long-term ventricular pacing percentage < 5%). At multivariate analysis, complete atrio-ventricular block independently predicted pacemaker dependency at follow-up (p = 0.019). Patients with persistent AV dysfunction showed a significant AV conduction time prolongation after TAVI (PR interval from 207 ± 50 to 230 ± 51, p = 0.02; QRS interval from 124 ± 23 to 147 ± 16, p < 0.01) compared to patients with recovery, in whom AV conduction parameters remained unchanged. Several patients receiving PPI after TAVI have recovery of AV conduction within a few weeks. Longer observation periods prior to PPI might be justified, and algorithms to minimize ventricular pacing should be utilized whenever possible.

Background: Cortisol levels, oxidative stress, and lower cerebral performance seem to be closely related. This study aimed to evaluate the question of whether exam stress affected oxidative stress and endothelial function parameters in the salivary samples of students. Methods: A total of 114 healthy students were recruited. All students were subjected to a 21-item DASS questionnaire to assess perceived stress. Cortisol levels, biomarkers of oxidative stress, and endothelial function were evaluated at T0, during the semester, and T1, in the morning before the exam, in saliva samples. In vitro, HUVECs were stimulated with cortisol, and oxidative stress and endothelial function parameters were evaluated. Results: At T1, cortisol levels were significantly increased compared with the levels during the semester. Moreover, exam results correlated inversely with the DASS score at T1. In addition, NOX2, H₂O₂ and endothelin-1 significantly increased, while NO bioavailability decreased. In vitro, HUVECs treatment with human cortisol determined the increase of oxidative stress and the decrease of endothelial function, in association with impaired eNOS phosphorylation. Conclusion: NOX2-mediated oxidative stress is a mechanism that could mediate cortisol-induced transient endothelial dysfunction during academic examination. Therefore, strategies to monitor or modulate oxidative stress could help students to reduce the impact of examination-related stress.