Cardiogen

Scientific advances in genomics are transforming healthcare and prevention. However, they also increase situations of uncertainty, which in turn increase vulnerability not only for patients and their families but also for professionals. Cardiogenetics plays a crucial role in preventing sudden death in young individuals, but it can pose complex challenges for healthcare teams. To study professionals' perspectives and experiences regarding cardiogenetics-related vulnerability, a national online survey was conducted in France to gather insight from professionals involved in the care pathway of individuals with cardiogenetic conditions. The survey targeted clinical geneticists, genetic counselors, cardiologists, nurses, and psychologists, in collaboration with the CARDIOGEN network. Out of 86 respondents, the majority (64%) reported experiencing vulnerability, which was not correlated with their profession, experience, or the organization of their clinics. Acknowledged vulnerabilities were mainly related to uncertainties regarding incomplete penetrance, variable expression, and genotype-phenotype disparities in cardiogenetics, exacerbated by the evolving interpretation of genetic data, due to the increased access to genomics. Additionally, the implications of these issues, particularly in cases of unexplained sudden deaths that necessitated genetic investigations and family follow up recommendations, raised further concerns. The reported vulnerabilities encompassed both the need for specialized knowledge and the structural complexities of teams combining skills in genetics and cardiology. In addition, the professionals' capacity to empathize can add a degree of vulnerability. Finally, it seems important to focus on how cardiogenetics teams are organized, particularly through close collaboration among genetics and cardiology units, which could help reduce this feeling of vulnerability.

Carnitine and its derivatives have recently been shown to protect cardiac metabolism and function in ischemic heart disease and other clinical conditions of myocardial ischemia. Potential mechanisms of this effect include an increase in glucose metabolism, a reduction of toxic effects of long-chain acyl-CoA and acyl-carnitine in myocytes, an increase in coronary blood flow and anti-arrhythmic effect. It has also been shown that propionyl-L-carnitine which penetrates faster than carnitine into myocytes is effective in inhibiting production of free radicals. Beneficial effects of carnitine supplementation have been demonstrated under a variety of clinical conditions such as acute cardiac ischemia, during extracorporeal circulation, in carnitine-dependent cardiomyopathy as well as in patients with chronic circulatory failure and in cardiogenic shock. However, further studies are required before carnitine administration could be recommended as a routine procedure in ischemic heart disease or before cardiopulmonary bypass.

The Szeged cardiomyopathy and ion channel diseases registry aims to establish a representative disease-specific registry based on the recruitment of patients with different cardiomyopathies and ion channel diseases followed at the Cardiology Center, University of Szeged. The registry collects patient data on the main forms of primary cardiomyopathies (hypertrophic, dilated, restrictive, arrhythmogenic right ventricular, left ventricular non-compact, tako-tsubo cardiomyopathy) and ion channel diseases (long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia). Patients with hypertrophic cardiomyopathy (388 patients) make up the largest group of patients in the registry. Patients with dilated cardiomyopathy (310 patients) and patients with the long QT syndrome (111 patients) form two other sizable groups. Analyzed data of the group of patients with hypertrophic cardiomyopathy indicate similar figures with regard to disease related mortality and morbidity and clinical parameters. Orv. Hetil., 2017, 158(3), 101-105.

Following our previous work on biochemical and clinical aspects of cardiogenic shock, we carried out an open study on 27 patients hospitalized in shock condition and investigated for the entire period of permanence in intensive care units (ICU). The subjects were treated with high doses of L-carnitine following previous results on the use of this molecule in conditions of oxidative damage due to acute cellular hypoxia. When compared with the data reported in the literature, the results obtained in this study show a surprisingly positive trend for the carnitine-treated patients in terms of survival rate to the cardiogenic shock. This finding and statistical analysis of the clinical parameters confirm the suggestion that L-carnitine could be credited with a new and interesting role in the therapy of cardiogenic shock.

OBJECTIVES: L-carnitine is an essential compound involved in cellular energy production through free fatty acid metabolism. It has been theorized that severe verapamil toxicity "shifts" heart energy production away from free fatty acids and toward other sources, contributing to profound cardiogenic shock. The primary study objective was to determine whether intravenous (IV) L-carnitine affects survival in severe verapamil toxicity. Secondary objectives were to determine the effects on hemodynamic parameters. The authors hypothesized that IV L-carnitine would increase both survival and hemodynamic parameters in severe verapamil toxicity. METHODS: This was a controlled, blinded animal investigation. Sixteen male rats were anesthetized, ventilated, and instrumented to record mean arterial pressure (MAP) and heart rate. Verapamil toxicity was achieved by a constant infusion of 5 mg/kg/hr. After 5 minutes a bolus of 50 mg/kg of either L-carnitine or normal saline was given. The experiment concluded when either 10% of baseline MAP was achieved or 150 minutes had elapsed. The data were analyzed using Kaplan-Meier analysis, log rank test, and analysis of variance. RESULTS: The median survival for the animals in the L-carnitine group was 140.75 minutes (interquartile range [IQR] = 98.6 to 150 minutes), and for those in the normal saline group it was 49.19 minutes (IQR = 39.02 to 70.97 minutes; p = 0.0001). At 15 minutes the MAP was 20.45 mm Hg greater in the animals in the L-carnitine group than in the animals in the normal saline group (95% confidence interval [CI] = 0.25 to 40.65; p = 0.047). CONCLUSIONS: When compared with saline, IV L-carnitine increases survival and MAP in a murine model of severe verapamil toxicity.

Ischemic stroke (IS), also known as ischemic cerebrovascular accident, is a serious consequence of cerebral ischemia characterized by high morbidity, disability, and mortality. The primary causes of IS include atherosclerosis, cardiogenic embolism, large artery occlusion, and small artery disease. The occurrence of IS involves multiple cellular death mechanisms such as vascular obstruction, inflammatory response, excitotoxicity, oxidative stress, as well as neuronal apoptosis, necroptosis, and pyroptosis. Despite the application of current drugs and therapeutic strategies in the treatment of IS, their efficacy remains limited, and they are often accompanied by adverse effects. Therefore, identifying novel and more effective treatment strategies is of critical importance. In recent years, oxytocin (OT) has attracted widespread attention due to its multiple biological effects in the central nervous system, especially its neuroprotective effects. OT can reduce ischemic damage by stabilizing the blood-brain barrier (BBB), inhibiting neuroinflammation, alleviating oxidative stress, regulating excitotoxicity, and calcium overload. Additionally, OT promotes neurovascular remodeling via the VEGF/BDNF axis and modulates Na⁺/K⁺-ATPase activity, GABA signaling pathways, and DNA methylation, thereby contributing to recovery after stroke. However, the pharmacokinetic characteristics of OT, limitations in delivery methods, and the challenges of individualized treatment restrict its clinical application. This review will summarize the mechanisms of OT in IS, discuss the challenges and limitations in its clinical application, and explore future development directions, including optimization of nasal delivery systems, development of nanodrug carriers, use of perfusion-weighted imaging to determine the therapeutic window, and personalized treatment strategies based on genetic profiling. The aim is to provide theoretical support and guidance for further research on OT and its clinical application.