IMPORTANCE Sodium glucose cotransporter 2 inhibitors reduce morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Clinicians may find estimates of the projected long-term benefits of sodium glucose cotransporter 2 inhibitors a helpful addition to clinical trial results when communicating the benefits of this class of drug to patients. OBJECTIVE To estimate the projected long-term treatment effects of dapagliflozin in patients with HFrEF over the duration of a patient's lifetime.DESIGN, SETTING, AND PARTICIPANTS Exploratory analysis was performed of Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF), a phase 3 randomized, placebo-controlled clinical trial conducted at 410 sites in 20 countries. Patients with an ejection fraction less than or equal to 40% in New York Heart Association functional classification II to IV and elevated plasma levels of N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Mean (SD) duration of follow-up was 17.6 (5.2) months.INTERVENTIONS Dapagliflozin, 10 mg, once daily vs placebo in addition to standard therapy. MAIN OUTCOMES AND MEASURESThe primary composite outcome was time to first hospitalization for heart failure, urgent heart failure visit requiring intravenous therapy, or cardiovascular death. The trial results were extrapolated to estimate the projected long-term treatment effects of dapagliflozin over the duration of a patient's lifetime for the primary outcome and the secondary outcome of death from any cause.RESULTS A total of 4744 patients (1109 women [23.4%]; 3635 men [76.6%]) were randomized in DAPA-HF, with a mean (SD) age of 66.3 (10.9) years. The extrapolated mean event-free survival for an individual aged 65 years from a primary composite end point event was 6.2 years for placebo and 8.3 years for dapagliflozin, representing an event-free survival time gain of 2.1 years (95% CI, 0.8-3.3 years; P = .002). When considering death from any cause, mean extrapolated life expectancy for an individual aged 65 years was 9.1 years for placebo and 10.8 years for dapagliflozin, with a gain in survival of 1.7 years (95% CI, 0.1-3.3; P = .03) with dapagliflozin. Similar results were seen when extrapolated across the age range studied. In analyses of subgroups of patients in DAPA-HF, consistent benefits were seen with dapagliflozin on both event-free and overall survival. CONCLUSIONS AND RELEVANCEThese findings indicate that dapagliflozin provides clinically meaningful gains in extrapolated event-free and overall survival. These findings may be helpful in communicating the benefits of this treatment to patients with HFrEF.TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03036124

Objective. To study the prognostic value of echocardiographic parameters of early cardiac remodeling in patients with hypertension (HTN) and obstructive sleep apnea (OSA). Design and methods. The study included 59 men with HTN and OSA (with an apnea/hypopnea index > 15 per hour). At baseline, all patients underwent polysomnography and echocardiography with an additional assessment of the global longitudinal strain (GLS). At baseline and at 12-month follow-up, a 6-minute walk test was performed. After 12 months, the clinical course of the disease was assessed. The criteria for an unfavorable course were episodes of hospitalization, the development of acute coronary syndrome, cerebral stroke, paroxysmal atrial fibrillation, worsening of chronic heart failure with a transition to a higher NYHA functional class. Results. In groups with favorable and unfavorable clinical course, some baseline echocardiographic parameters differed significantly: interventricular septal thickness (p = 0,037), left ventricular myocardial mass index (LVMI) (p = 0,003), tricuspid annular plane systolic excursion (TAPSE) (p < 0.001), GLS (p = 0,019), peak tricuspid regurgitation (p = 0,027), left atrial volume index (p = 0,048). Regression analysis showed that baseline TAPSE and LVMI had predictive value for an unfavorable clinical course. Conclusions. Our results confirm that certain echocardiographic parameters, in particular, LVMI and TAPSE, are predictors of the development and progression of cardiovascular complications in OSA patients.

Aim. To study the associations of hypoxia-inducible factor-1 alpha (HIF-1α) gene polymorphism (rs11549465) with the clinical course of heart failure (HF) with reserved ejection fraction (HFpEF) in patients with obesity and moderate and severe obstructive sleep apnea (OSA).Material and methods. The study included 76 men with HFpEF and OSAS. Patients underwent a polysomnography, echocardiography, and a 6-minute walk test. In addition, apnea/hypopnea index was calculated, and the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) was assessed. HIF1A gene polymorphisms (rs11549465) were analyzed using polymerase chain reaction. After 12-month follow-up, the clinical course of HF was assessed.Results. The T/T genotype of the HIF1A gene was associated with a high risk of HF progression (p=0,004), development of supraventricular premature beats (p=0,004) and atrial fibrillation (p=0,039). Carrying the T/T genotype was associated with severe OSA (p=0,006) and increased NT-proBNP (p=0,044), and also correlated with certain echocardiographic characteristics of myocardial remodeling.Conclusion. T/T genotype of the HIF1A gene is associated with OSA severity and increased NT-proBNP, as well as with the severity of left and right heart remodeling. The carriage of this genotype was associated with an unfavorable course of HF and an increased risk of atrial fibrillation in patients with HFpEF and OSA.

Aim. To study approaches to the treatment of chronic heart failure (CHF) with reduced and mid-range left ventricular ejection fraction (LVEF) in patients with arterial hypertension (AH) against the background of obstructive sleep apnea (OSA).Material and methods. The study included 136 patients with CHF and AH. Inclusion criteria for the study: 1) moderate and severe OSA (with an apnea/hypopnea index of more than 15 per hour); 2) II-IV functional class of CHF according to NYHA; 3) the level of brain natriuretic peptide precursor (NT-proBNP) ≥125 pg/ml; 3) LVEF <50%; 4) the duration of hypertension is at least 2 years. Patients received drug therapy, including beta-blockers, mineralocorticoid receptor antagonists, diuretics, ACE inhibitors or angiotensin receptor inhibitors or valsartan/sacubitrile. After 12 months of followup, the patients were divided into 2 groups depending on the medication being administered. Group 1 included patients (n = 50) receiving therapy with valsartan/sacubitril, group 2 included patients (n = 86) receiving therapy without this drug. Effective CPAP-therapy also was registered in each group.Results. In patients with CHF who received valsartan/sacubitril, disease progression was recorded in 28% of cases, while in patients who did not receive therapy with this drug, an unfavorable course of CHF was recorded in 42.8% (p = 0.001). In group 1, the NT-proBNP level significantly (p = 0.034) decreased by 34%, while in group 2, a significant (p = 0.002) increase in biomarker levels was revealed by 35.5%. In the group of patients receiving therapy with valsartan/sacubitril an increase in LVEF (p = 0.007) was revealed by 12.5%. In group 1, an increase in exercise tolerance was achieved in the form of a significant (p = 0.012) increase in the distance of the six-minute walk test by 18.2%, while in group 2, the six-minute walk distance decreased by 19.2% (p = 0.034). In the subgroup of patients receiving CPAP therapy in combination with valsartan/sacubitril therapy (n=8), LVEF increased by 11.6% (p = 0.043), the six-minute walk test distance increased by 29.7% (p = 0.046), and NT-proBNP decreased by 22.5% (p = 0.039), while in the group of patients who received only CPAP therapy (n=19).Conclusion. The most significant slowdown in the rate of progression of CHF in patients with AH associated with OSA, an increase in exercise tolerance, as well as the most pronounced tendency to the reverse development of pathological echocardiographic changes in the myocardium when using valsartan/sacubitrile in drug therapy in combination with effective hardware CPAP therapy.