On November 21, Director General of Almazov Centre Evgeny Shlyakhto chaired the International Expert Meeting on the project “Neuromodulation-based approaches to prevention and treatment of heart failure” carried out by the Centre’s team under the agreement with the Ministry of Science and Higher Education of the Russian Federation. The members of the International Advisory Board are prominent experts in heart failure.
In his opening speech Evgeny Shlyakhto emphasized the great social significance of the heart failure problem in the modern world and the importance of translational and basic research aimed at introducing the latest achievements into practice. Mikhail Galagudza, Director of the Institute of Experimental Medicine, Corresponding Member of the Russian Academy of Sciences and Evgeny Mikhailov, Deputy Director of the Institute of Heart and Vessels, gave two presentations. They spoke about the main results obtained from the project in 2022 and outlined the development plans in this area. The presentations were followed by an open discussion regarding the further implementation of the project, including new methodological approaches and challenging scientific tasks.
Currently, there are more than 3.5 million patients with chronic heart failure in Russia. Heart failure affects more than 28 million patients worldwide and is increasing in prevalence. The predictions suggest that this number will increase by 20 to 40 % by 2030. Despite certain progress in the prevention and treatment of this condition, the prognosis in most patients remains poor, which dictates the need to find new ways to improve treatment outcomes.
The main goal of the project is to study the fundamental mechanisms of the autonomic nervous system involved in the pathogenesis of circulatory diseases and to develop new technologies for the prevention and treatment of heart failure based on neuromodulation. In 2022, the project team obtained priority research data presented in 11 publications in leading international journals (International Journal of Molecular Sciences, Journal of Cardiovascular Development and Disease, Journal of Clinical Medicine, journal of Geriatric Cardiology, The Anatomical Record, Diagnostics, etc.), three successfully defended PhD and one doctoral theses.
A 3D mathematical model of ischemia-reperfusion injury in the rat and human heart was developed, making it possible to predict and heed the effect of adipose tissue hormones and vagal stimulation on the process of myocardial damage and the formation of rhythm disturbances. Experimental studies on rodents have shown that a short-term exposure to leptin released from adipose tissue leads to cardiac protection and a decreased expression of miR-208a in the myocardium. The experiments with modeling of primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension have shown that the elimination of sympathetic effects on the heart and lungs is associated with decreased manifestations of this condition and reduces morphological signs of wall hypertrophy of the smaller branches of the pulmonary artery. New molecular mechanisms associated with the favorable effects of sympathetic denervation on the course of pulmonary hypertension were identified. A new large animal model of atrial fibrillation was developed and validated using high-frequency burst pacing of certain cardiac structures.
New data on the types and prevalence of orthostatic reactions in patients with heart failure were obtained. Research is underway to study the management of arterial hypotension, including orthostatic hypotension, in patients with and without severe heart failure, with indications for heart transplantation. New data were obtained on the possibility of using transcutaneous electrical spinal cord stimulation to treat hypotension.
New approaches are being developed to the pulmonary and renal artery denervation methods on models of pulmonary and systemic arterial hypertension. Work has started on transvascular laser ablation of perivascular nerves in the treatment of chronic CVDs with a high risk of developing heart failure (stage A). New data have been obtained on the risk of impaired renal function associated with a pronounced blood pressure lowering effect after renal denervation.
In experimental studies on parasympathetic denervation of the heart, the effect of impaired autonomic regulation on exercise tolerance was studied for the first time and it was proved that regular physical training helps to partially restore autonomic nervous activity (heart rate variability) and improve exercise tolerance. This may be especially true for patients with autonomic dysfunction syndromes and after heart transplantation when complete organ denervation is observed.
Based on a large clinical material, an assessment was made to identify serious deficiencies in predicting survival and cardiovascular events in Russian patients with chronic heart failure. Based on the analysis of a complex of biochemical and clinical parameters, new region-specific risk prediction models, including for patients receiving high-tech medical care using cardiac implantable electrophysiological devices (stages C and D according to the modern classification) were developed. A scale for predicting the development of heart failure in the medium term was developed for patients with diabetes mellitus, cardiovascular risks, those receiving combination therapy, including with SGLT2 inhibitors.
The findings obtained from this translational research project show scientific novelty and practical importance and can be directly introduced into clinical practice.
The Advisory Board noted the significant scope of tasks as well as the exceptional methodological and scientific potential of the research. Internationally recognized experts highly praised the well-coordinated work of the project team (105 participants in 2021). The experts expressed their wishes for a prompt implementation of developments in the practice.