Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the myocardium. Conventionally, the incidence of this disease was estimated at 1: 500 people, but it is probably higher and amounts to about 1: 200 cases. In Poland, this gives 76,000 to 190,000 people. HCM is asymptomatic in some people. In others, it is associated with progressive left ventricular diastolic dysfunction due to myocardial hypertrophy and fibrosis, eventually leading to systolic dysfunction and progressive heart failure. Both heart failure with preserved left ventricular ejection fraction (LVEF) and reduced LVEF are inevitably associated with impaired physical function, often affecting young, professionally and socially active individuals. An additional significant problem in patients with HCM is arrhythmias leading to an increased risk of sudden death.~At present, for patients with HCM, there is no treatment available, which could inhibit the progression of the disease. The methods of treatment proposed so far, affecting the various pathogenic mechanisms of hypertrophic cardiomyopathy, have proved to be ineffective.~The aim of the project is therefore to seek a therapeutic solution for a disease for which standard medicine does not yet offer satisfactory solutions.~Empagliflozin is a reversible, potent and selective competitive inhibitor of sodium-glucose co-transporter-2 (SGLT2). It is the main transporter responsible for the reabsorption of glucose from the glomerular filtrate into the bloodstream. Its inhibition in people with type 2 diabetes leads to an increase in urinary glucose excretion and a decrease in its concentration in the blood. In the study in patients with type 2 diabetes and high cardiovascular risk, the use of empagliflozin was associated with a significant decrease in mortality and the number of hospitalizations due to heart failure. The mechanisms responsible for beneficial effects of empagliflozin are not fully understood. It is underlined that effects leading to a reduction of oxidative stress, improvement of diastolic function, inhibition of myocardial fibrosis and, what is important, improvement of myocardial energy status and reduction of cardiomyocyte calcium overload, increase of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity, which are important pathophysiological mechanisms of HCM, leading to progressive myocardial hypertrophy and the development of heart failure.~The proposed intervention will be administration of empagliflozin at a standard dose of 10 mg daily for a period of 12 months. Patients with diagnosed diabetes will be excluded from the study. Patients (n = 250) will be randomized in a double-blind fashion to empagliflozin or placebo group. The primary endpoint of the study will be the change in peak oxygen uptake (VO2 max) measured in a cardiopulmonary exercise test. VO2max is an objective indicator of physical performance and will be evaluated before and after empagliflozin or placebo treatment. Secondary endpoints will be a change in the maximum left ventricular wall thickness, left ventricular mass, parameters of diastolic dysfunction, severity of myocardial fibrosis and improvement of its energy status.~An important aspect of the study will be the genetic analysis of the study group. Data in both human and experimental studies indicate that the benefits of treatment may be dependent on the patient's genotype. The pathomechanisms of heart failure development differ depending on the mutation found and the prognosis of patients is the worst in the case of HCM phenocopies as well as in patients with pathogenic variants in sarcomeric genes. It is therefore justified to examine the genetic profile of the population being studied. For this purpose, next generation sequencing (NGS) with whole exome sequencing (WES) is planned. This will detect both known and unknown variants in the genes responsible for developing HCM. In addition, the investigators hypothesized that the beneficial cardiac effects of empagliflozin may be dependent on genes involved in the pathophysiology of diabetes, and a separate research task with the participation of a foreign partner (University of Eastern Finland) was devoted to this issue.~The investigators believe that the social benefit of the project is greater than its costs, giving the prospect of treating a disease for which modern medicine turns out to be insufficient. Preventing the development of heart failure among patients with HCM, apart from the benefit for the patients themselves, will also translate into economic benefits for the health care and the social systems
The proposed intervention will be administration of empagliflozin at a standard dose of 10 mg daily for a period of 12 months. Patients with diagnosed diabetes will be excluded from the study. Patients (n = 250) will be randomized in a double-blind fashion to empagliflozin or placebo group. The primary endpoint of the study will be the change in peak oxygen uptake (VO2 max) measured in a cardiopulmonary exercise test. VO2max is an objective indicator of physical performance and will be evaluated before and after empagliflozin or placebo treatment.