Semaglutide in Cardiometabolic Diseases: SELECTing the Target Population.

Cardiovascular diseases remain the main cause of death and disability worldwide. Despite the tremendous improvement in pharmacological, minimally invasive and rehabilitative strategies, global deaths due to cardiovascular diseases are still increasing. Additional risk factors have been recently proposed, and thanks to scientific progress, novel drugs for the control of the main risk factors focusing on the cardiometabolic pathways have been identified. Glucagon-like peptide-1 (GLP-1) receptor agonists represent an innovative step in the management of patients affected by type 2 diabetes mellitus. In addition to their significant efficacy on glycemic homeostasis, some members of this class of drugs have indications in the treatment of obesity. Furthermore, accumulated evidence in the literature has finally suggested a protective role in cardiovascular health. The possible role of GLP-1R agonist drugs (GLP-1RAs) on the mechanisms underlying chronic inflammation and the almost ubiquitous distribution of GLP-1 receptors could explain the enormous versatility of these drugs. Semaglutide is a GLP-1RA recently proven to be effective in cardiovascular outcomes. In the present article, we will review the available data on semaglutide in light of the most recent publications to better characterize the target population achieving cardiovascular benefits.

Impact of synchronous atrioventricular delay optimization on left ventricle flow force angle evaluated by echocardiographic particle image velocimetry.

PURPOSE: To evaluate the improvement in electrical synchrony and left ventricle (LV) hemodynamics provided by combining the dynamic atrioventricular delay (AVD) of SyncAVTM CRT and the multiple LV pacing sites of MultiPoint pacing (MPP). METHODS: Patients with LBBB and QRS duration (QRSd) > 140 ms implanted with a CRT-D or CRT-P device and quadripolar LV lead were enrolled in this prospective study. During a post-implant follow-up visit, QRSd was measured from 12-lead surface electrograms by experts blinded to pacing configurations. QRSd reduction relative to intrinsic rhythm was evaluated during biventricular pacing (BiV) and MPP for two AVDs: nominal (140/110 ms paced/sensed) and SyncAV (patient-optimized SyncAV offset [10-60 ms] minimizing QRSd). Echocardiography particle imaging velocimetry (Echo-PIV) analysis was performed for each configuration. The resulting hemodynamic force LV flow angle (φ) was analyzed, which ranges from 0o (predominantly base-apex forces) to 90o (predominantly transverse forces). Higher angles indicate more energy dissipation at lateral walls due to transverse flow; lower angles indicate healthier flow aligned with the longitudinal base-apex path of the pressure gradient. RESULTS: Twelve patients (58% male, 17% ischemic, 32±7% ejection fraction, 165 ± 18 ms intrinsic QRSd) completed QRSd and Echo-PIV assessment. Relative to intrinsic rhythm, BiV and MPP with nominal AVD reduced QRSd by 10 ± 9% and 12 ± 9%, respectively. BiV+SyncAV and MPP+SyncAV further reduced QRSd by 19 ± 8%, (p < 0.05 vs. BiV with nominal AVD) and 23 ± 9% (p < 0.05 vs BiV+SyncAV), respectively. Echo-PIV showed similar sequential hemodynamic improvements. LV flow angular orientation during intrinsic activation (46 ± 3o) reduced with BiV+SyncAV (37 ± 4o, p < 0.05 vs intrinsic) and further with MPP+SyncAV (34 ± 4o, p < 0.05 vs BiV+SyncAV). CONCLUSION: These results suggest that SyncAV may improve electrical synchrony and influence LV flow patterns in patients suffering from heart failure compared to conventional CRT with a fixed AVD, with further improvement observed by combining with MPP.

The Impact of the COVID-19 Outbreak on Patients' Adherence to PCSK9 Inhibitors Therapy.

PCSK9 inhibitors (PCSK9i) are monoclonal antibodies that have been shown to be effective in reducing both LDL cholesterol (LDL-C) values and major cardiovascular events in patients at high cardiovascular risk. Adherence to PCSK9i is critical for the success of the treatment. The aim of the present study is to evaluate patients' adherence to PCSK9i during the COVID-19 pandemic. Patients referred to the Cardiac Diagnostic Unit of the University of Campania "Luigi Vanvitelli" Naples, taking PCSK9i, and who missed the cardiological follow-up visit during the first national COVID-19 lockdown (9 March-17 May 2020), were included. Each patient underwent medical teleconsultation to collect current clinical conditions, adherence to drug treatments, and lipid profile laboratory tests. Among 151 eligible patients, 20 were excluded for missing or untraceable telephone numbers and one for refusing to join the interview. The selected study population consisted of 130 patients (64 ± 9 years, 68% males), of whom 11 (8.5%) reported a temporary interruption of the PCSK-9 therapy for a mean period of 65 ± 1.5 days. The non-adherent patients showed a marked increase in LDL-C than in the pre-pandemic period (90.8 ± 6.0 vs. 54.4 ± 7.7 mg/dL, p < 0.0001), and 82% of patients moved out of the LDL-C therapeutic range. The non-adherent group was more likely to have a very high cardiovascular risk compared to the adherent group (81.8 vs. 33.6%, p < 0.001). Causes of interruption included drug prescription failure (63.6%) due to temporary interruption of the non-urgent outpatient visits and failure in drug withdrawal (36.4%) due to patients' fear of becoming infected during the pandemic. The COVID-19 lockdown caused a remarkable lack of adherence to PCSK9i therapy, risking negative implications for the health status of patients at high cardiovascular risk. Facilitating patients' access to PCSK9i and enhancing telemedicine seem to be effective strategies to ensure the continuity of care and appropriate management of these patients.

Regulation of Inflammation and Oxidative Stress by Formyl Peptide Receptors in Cardiovascular Disease Progression.

G protein-coupled receptors (GPCRs) are the most important regulators of cardiac function and are commonly targeted for medical therapeutics. Formyl-Peptide Receptors (FPRs) are members of the GPCR superfamily and play an emerging role in cardiovascular pathologies. FPRs can modulate oxidative stress through nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species (ROS) production whose dysregulation has been observed in different cardiovascular diseases. Therefore, many studies are focused on identifying molecular mechanisms of the regulation of ROS production. FPR1, FPR2 and FPR3 belong to the FPRs family and their stimulation triggers phosphorylation of intracellular signaling molecules and nonsignaling proteins that are required for NADPH oxidase activation. Some FPR agonists trigger inflammatory processes, while other ligands activate proresolving or anti-inflammatory pathways, depending on the nature of the ligands. In general, bacterial and mitochondrial formylated peptides activate a proinflammatory cell response through FPR1, while Annexin A1 and Lipoxin A4 are anti-inflammatory FPR2 ligands. FPR2 can also trigger a proinflammatory pathway and the switch between FPR2-mediated pro- and anti-inflammatory cell responses depends on conformational changes of the receptor upon ligand binding. Here we describe the detrimental or beneficial effects of the main FPR agonists and their potential role as new therapeutic and diagnostic targets in the progression of cardiovascular diseases.

Non Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients Scheduled for Electrical Cardioversion: A Real-Life Propensity Score Matched Study.

AIM: The aim of the present study was to assess the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients undergoing electrical cardioversion (EC). METHODS: A propensity score-matched analysis was performed in order to identify two homogeneous groups including AF patients on NOACs and VKAs treatment scheduled for EC. The primary safety endpoint was major bleeding. The composite of stroke, transient ischemic attack (TIA) and systemic embolism (SE) was the primary effectiveness endpoint. The discontinuation rate of anticoagulant therapy was assessed. RESULTS: A total of 495 AF patients on NOACs therapy and scheduled for EC were compared to 495 VKAs recipients. No statistically significant differences in the incidence of both major bleeding (1.01% versus 1.4%; P= 0.5) and thromboembolic events (0.6% versus 0.8%; P= 0.7) were observed during a mean follow-up of 15 ± 3 months. The discontinuation rate of NOACs was significantly lower compared to VKAs (1.6% versus 3.6%, P=0.04). CONCLUSION: We showed a safe and effective clinical profile of NOACs among AF patients scheduled for electrical cardioversion in real-life setting. Patients on NOACs therapy showed a lower discontinuation rate compared to those on VKAs.

Transcatheter Aortic Valve Replacement and Cardiac Resynchronization Therapy in Cancer-Related Cardiotoxicity.

Cardiotoxicity related to antineoplastic agents is a rising and growing issue, therefore early recognition and prompt management can impact on the overall prognosis of cancer patients. We report the case of a 70-year-old woman without cardiovascular risk factors, with a medical history of non-Hodgkin lymphoma and chronic myeloid leukemia treated with chemotherapy and radiotherapy, who underwent transcatheter aortic valve replacement for severe aortic stenosis and cardiac resynchronization therapy for further development of complete left bundle branch block, with a significant improvement of her functional status and left ventricle systolic function in a long-term follow-up.