Melatonin mitigates oxidative damage induced by anthracycline: a systematic-review and meta-analysis of murine models.

Background: Oxidative stress induced by the excessive production of reactive oxygen species is one of the primary mechanisms implicated in anthracycline (ANT)-induced cardiotoxicity. There is a strong clinical need for a molecule capable of effectively preventing and reducing the oxidative damage caused by ANT. In vitro and in vivo studies conducted in mice have shown that melatonin stimulates the expression of antioxidative agents and reduces lipid peroxidation induced by ANT. Methods: We investigated this issue through a meta-analysis of murine model studies. The outcome of the meta-analysis was to compare oxidative damage, estimated by products of lipid peroxidation (MDA = Malondialdehyde) and markers of oxidative stress (SOD = Superoxide Dismutase, GSH = Glutathione), along with a marker of cardiac damage (CK-MB = creatine kinase-myocardial band), assessed by measurements in heart and/or blood samples in mice undergoing ANT chemotherapy and assuming melatonin vs. controls. The PubMed, OVID-MEDLINE and Cochrane library databases were analysed to search English-language review papers published from the inception up to August 1st, 2023. Studies were identified by using Me-SH terms and crossing the following terms: "melatonin", "oxidative stress", "lipid peroxidation", "anthracycline", "cardiotoxicity". Results: The metanalysis included 153 mice administered melatonin before, during or immediately after ANT and 153 controls from 13 studies. Compared with controls, the levels of all oxidative stress markers were significantly better in the pooled melatonin group, with standardized mean differences (SMD) for MDA, GSH and SOD being -8.03 ± 1.2 (CI: -10.43/-5.64, p < 0.001), 7.95 ± 1.8 (CI: 4.41/11.5, p < 0.001) and 3.94 ± 1.6 (CI: 0.77/7.12, p = 0.015) respectively. Similarly, compared with controls, CK-MB levels reflecting myocardial damage were significantly lower in the pooled melatonin group, with an SMD of -4.90 ± 0.5 (CI: -5.82/-3.98, p < 0.001). Conclusion: Melatonin mitigates the oxidative damage induced by ANT in mouse model. High-quality human clinical studies are needed to further evaluate the use of melatonin as a preventative/treatment strategy for ANT-induced cardiotoxicity.

Right Heart Catheterization: An Antecubital Vein Approach to Reduce Fluoroscopy Time, Radiation Dose, and Guidewires Need.

Antecubital access for right heart catheterization (RHC) is a widespread technique, even though there is a need to clarify if there are differences and significant advantages compared to proximal vein access. To pursue this issue, we retrospectively identified patients who underwent RHC in our clinic over a 7 year period (between January 2015 and December 2022). We revised demographic, anthropometric, and procedural data, including the fluoroscopy time, the radiation exposure, and the use of guidewires. The presence of any complications was also assessed. In patients with antecubital access, the fluoroscopy time and the radiation exposure were lower compared to proximal vein access (6 vs. 3 min, mean difference of 2 min, CI 95% 1-4 min, p < 0.001 and 61 vs. 30 cGy/m2, mean difference 64 cGy/m2, CI 95% 50-77, p < 0.001). The number of patients requiring the use of at least one guidewire was lower in the group undergoing RHC through antecubital access compared to proximal vein access (55% vs. 43%, p = 0.01). The feasibility was optimal, as just 0.9% of procedures switched from antecubital to femoral access, with a negligible rate of complications. The choice of the antecubital site exhibits advantages, e.g., a shorter fluoroscopy time, a reduced radiation dose, and a lower average number of guidewires used compared to proximal vein access.

Atrioventricular conduction in PM recipients after transcatheter aortic valve implantation: Implications using Wenckebach point measurement.

Background: Atrioventricular (AV) conduction disturbances requiring permanent pacemaker implantation (PPI) are a common complication after transcatheter aortic valve implantation (TAVI). However, a significant proportion of patients might recover AV conduction at follow-up. Objectives: The aim of our study was to evaluate the recovery of AV conduction by determination through Wenckebach point in patients with PPI and therefore identify patients who could benefit from device reprogramming to avoid unnecessary RV pacing. Methods: We enrolled 43 patients that underwent PM implantation after TAVI at our Department from January 2018 to January 2021. PM interrogation was performed at follow-up and patients with native spontaneous rhythm were further assessed for AV conduction through WP determination. Results: A total of 43 patients requiring a PM represented the final study population, divided in patients with severely impaired AV conduction (no spontaneous valid rhythm or WP < 100; 26) and patients with valid AV conduction (WP ≥ 100; 17). In the first group patients had a significantly higher number of intraprocedural atrioventricular block (AVB) (20 vs. 1, p < 0.005), showed a significant higher implantation depth in LVOT (7.7 ± 2.2 vs. 4.4 ± 1.1, p < 0.05) and lower ΔMSID (-0.28 ± 3 vs. -3.94 ± 2, p < 0.05). Conclusion: AV conduction may recover in a significant proportion of patients. In our study, valve implantation depth in the LVOT and intraprocedural AV block are associated with severely impaired AV conduction. Regular PM interrogation and reprogramming are required to avoid unnecessary permanent right ventricular stimulation in patients with AV conduction recovery.

Mitochondrial quality control mechanisms as molecular targets in cardiac ageing.

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Advancing age is a major risk factor for developing cardiovascular disease because of the lifelong exposure to cardiovascular risk factors and specific alterations affecting the heart and the vasculature during ageing. Indeed, the ageing heart is characterized by structural and functional changes that are caused by alterations in fundamental cardiomyocyte functions. In particular, the myocardium is heavily dependent on mitochondrial oxidative metabolism and is especially susceptible to mitochondrial dysfunction. Indeed, primary alterations in mitochondrial function, which are subsequently amplified by defective quality control mechanisms, are considered to be major contributing factors to cardiac senescence. In this Review, we discuss the mechanisms linking defective mitochondrial quality control mechanisms (that is, proteostasis, biogenesis, dynamics, and autophagy) to organelle dysfunction in the context of cardiac ageing. We also illustrate relevant molecular pathways that might be exploited for the prevention and treatment of age-related heart dysfunction.