Recent Advances in Understanding the Molecular Mechanisms of SGLT2 Inhibitors in Atrial Remodeling.

Atrial cardiomyopathy and remodeling play pivotal roles in the development of atrial fibrillation (AF) and heart failure (HF), involving complex changes in atrial structure and function. These changes facilitate the progression of AF and HF by creating a dynamic interplay between mechanical stress and electrical disturbances in the heart. Sodium-glucose cotransporter 2 inhibitors (SGLT2is), initially developed for the management of type 2 diabetes, have demonstrated promising cardiovascular benefits, being currently one of the cornerstone treatments in HF management. Despite recent data from randomized clinical trials indicating that SGLT2is may significantly influence atrial remodeling, their overall effectiveness in this context is still under debate. Given the emerging evidence, this review examines the molecular mechanisms through which SGLT2is exert their effects on atrial remodeling, aiming to clarify their potential benefits and limitations. By exploring these mechanisms, this review aims to provide insights into how SGLT2is can be integrated into strategies for preventing the progression of atrial remodeling and HF, as well as the development of AF.

Predictors for the Development of Major Adverse Limb Events after Percutaneous Revascularization-Gender-Related Characteristics.

Background and Objectives: Revascularization has been proven to be superior to medication for symptom improvement in patients with peripheral arterial disease (PAD). There are well known gender differences in therapeutic strategies for PAD. The influence of gender on post-angioplasty prognosis is not fully understood though. The present study aims to identify potential peculiarities between men and women undergoing peripheral angioplasty, as well as factors responsible for those differences. Material and methods: 104 consecutive subjects (50 women and 54 men) who underwent percutaneous angioplasty (PTA) between January and October 2019 for symptomatic PAD were included. Demographics, PAD history, cardiovascular risk factors, comorbidities, the associated coronary or cerebrovascular diseases, biological parameters, drug-treatment and PTA type and technique were taken into account. The follow-up period was 2 years, during which major adverse limb events (MALE) were documented. Results: The mean age was 67 ± 10 years. Women were 4 years older than the men (69 ± 10 years vs. 65 ± 9.2 years-p = 0.04). Smoking was more prevalent in men (p = 0.0004), while other cardiovascular risk factors did not differ significantly. The mean follow-up of the two groups was 21 ± 2.4 months. Women had infra-inguinal involvement more frequently (78%), while men exhibited mixed disease, with supra + infra-inguinal (37%) or solely supra-inguinal (20.3%) involvement (p = 0.0012). Rates of MALE were similar in the two groups (p = 0.914). Gender did not influence the incidence of PAD-related adverse events. The only parameter that proved to have a significant influence on the occurrence of MALE was the ankle-brachial index (ABI). A value below 0.5 was found to be an independent predictor for MALE (p = 0.001). Conclusions: There was no significant difference in the incidence rates of MALE between the two genders over a 2-year follow-up period post-PTA. Regardless of sex, an ankle-brachial index value below 0.5 was the sole independent predictor for limb-related adverse events.

General Anesthesia Improves Efficiency of High-Power Short-Duration Catheter Ablation for Atrial Fibrillation: Comparison with Mild Conscious Sedation.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia globally. High-power, short-duration radiofrequency (RF) catheter ablation (CA) for AF has recently emerged, reducing ablation times and enhancing patient tolerability with comparable efficacy and safety. While the benefits of general anesthesia (GA) for standard-power, standard-duration CA are well-established, data comparing GA to mild conscious sedation (MCS) for high-power, short-duration CA are limited. METHODS: We included patients undergoing high-power, short-duration CA for AF under GA (group 1) or MCS (group 2). Procedural characteristics, success rates, and mid-term outcomes were compared. RESULTS: In total, 131 patients, 47 in the GA group and 84 in the MCS group, were included. CA was performed for paroxysmal AF in 34 patients in group 1 (72.3%) and 68 patients in group 2 (80.9%). We found lower a mean total procedure time (100 [90-120] vs. 160 [130-180] min, p < 0.0001), lower radiation exposure (932.5 [625-1716] vs. 2445 [1228-4791] µGy, p < 0.0001 and 4.5 [3-7.1] 7.3 [4.2-13.5] min, p = 0.0003) and fewer RF applications (71 [54.8-83.8] vs. 103 [88.5-120.5], p < 0.0001) in the GA group. No major complications occurred. The 6-month AF recurrence rate was comparable between the groups (21.2% vs. 33.3%, p = 0.15). CONCLUSION: In patients undergoing high-power, short-duration RFCA for AF, the use of GA is associated with better procedural efficiency while simultaneously associated with an early recurrence rate comparable to MCS.

Particularities of Catheter Ablation in Women with Atrial Fibrillation and Associated Ischemic Heart Disease.

BACKGROUND: Atrial fibrillation is more common in men, but in the presence of ischemic heart disease, this arrhythmia is more frequent in women. However, like in coronary heart disease, women with atrial fibrillation are suboptimally treated. METHODS: To identify particularities of ablation, in women with atrial fibrillation and ischemic heart disease. RESULTS: 29 women and 26 men, with documented ischemic heart disease and atrial fibrillation, who underwent catheter ablation, were admitted in the study. No significant differences were registered regarding the heart rate control treatment. Electrical cardioversion was significantly higher in men, while pharmacological cardioversion was predominantly recommended in women. The ablation was performed later in women, after 2.55 ± 1.84 years versus 1.80 ± 1.05 in men (p = 0.05). The time elapsed until the ablation was performed was statistically correlated with atypical symptomatology and with the number of antiarrhythmics used prior to the ablation. There were no significant differences for the relapse of atrial fibrillation at 3 months. Quality of life at 3 months after ablation was increased in both groups. CONCLUSION: Catheter ablation is performed much later in women, and the causes responsible for this delay would be more atypical symptoms and a greater number of antiarrhythmics tried before the ablation.

The Role of IL-6 and ET-1 in the Diagnosis of Coronary MicroVascular Disease in Women.

BACKGROUND: Microvascular angina is a common clinical entity, with about a three-fold higher frequency in women. The pathogenesis of microvascular angina has not been much studied, but inflammation and endothelial dysfunction have been incriminated as the main mechanisms of this disease. Methoss: Our purpose was to analyze whether certain inflammatory markers, i.e., interleukin 6 (IL-6) and endothelin 1 (ET-1), can play a role in the diagnosis of microvascular angina in women. RESULTS: Ninety women with ischemic heart disease were divided into two groups, based on their affliction with either microvascular or macrovascular disease. In general, the levels of IL6 and ET1 were similar between the two groups. Analyzing these marker levels according to the number of coronary lesions, we obtained an increased IL6 value that was similar for patients with microvascular angina, one-vessel, and two-vessel coronary disease, but significantly lower than in women with three-vessel coronary lesions. Also, in microvascular angina, IL6 level was correlated with the NYHA IV functional class. Unexpectedly, the level of ET1 was correlated with left ventricular systolic dysfunction. CONCLUSIONS: In women with an increased suspicion of microvascular angina, in whom microvascular dysfunction cannot be tested invasively, IL-6 level, unlike the ET-1 level, might be considered a diagnostic marker of this disease.

The role of multimodal imaging in the diagnosis of an asymptomatic patient with congenital anomaly.

Anomalous left coronary artery from the pulmonary artery (ALCAPA) syndrome is a rare congenital coronary anomaly, which can cause potentially fatal complications, such as heart failure, myocardial infarction and sudden cardiac death. Only a few patients left untreated survive to adulthood. We highlight the importance of multimodal imaging in the diagnosis of ALCAPA syndrome in a young asymptomatic female patient with inducible ischemia on exercise. The patient was successfully treated with surgery.

Leptin, Galectin-3 and Angiotensin II Type 1 Receptor Polymorphism in Overweight and Obese Patients with Heart Failure - Role and Functional Interplay.

BACKGROUND AND AIMS: Leptin, one of the best-known adipocytes, together with the renin-angiotensin-aldosterone system and galectin-3 are important players in inflammation, arterial hypertension and heart failure pathophysiology. Moreover, uninucleotide A1166C polymorphism is associated with hypertension and poor prognosis in heart failure. The aim of the study was to investigate a possible relationship between leptin serum values, specific heart failure biomarkers and the presence of AT1 receptor A1166C polymorphism in overweight and obese heart failure patients. METHODS: The study included 88 consecutive overweight and obese patients admitted for decompensated heart failure. NT-proBNP, MR-proANP, galectin-3 and leptin levels were determined on the arrival day. Genotyping of the A1166C allele - AT1 receptor gene was performed in all patients in order to find variants. RESULTS: We found a strong positive correlation (r = 0.347, p = 0.001) between leptin serum concentrations and BMI. Leptin levels were not correlated with heart failure biomarkers (NT-proBNP, MR-proANP and galectin-3). All homozygote CC variants were hypertensive, but we registered no significant difference in genetic AC and AA variants distribution between hypertensive and normotensive. Leptin was not significantly modified by the presence of potentially pathogenic A1166C-AT 1 receptor genotypes (AC + CC). But, galectin-3 was found in higher concentrations in patients with heterozygous and homozygous A1166C mutations. CONCLUSION: Overweight and obese patients with heart failure display high leptin serum levels. Leptin does not offer incremental prognostic value in heart failure overweight and obese patients. But, galectin-3 was found in higher concentrations in patients with heterozygous and homozygous A1166C mutations, suggesting a worse prognosis probably due to more advanced cardiac fibrosis.