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.To estimate the projected long-term treatment effects of dapagliflozin in patients with HFrEF over the duration of a patient's lifetime.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.Dapagliflozin, 10 mg, once daily vs placebo in addition to standard therapy.The 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.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.These 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.ClinicalTrials.gov Identifier: NCT03036124.
Hypertrophic cardiomyopathy (HCM) is a frequent cardiovascular pathology caused by a huge number of mutations in sarcomere-associated proteins. This genetic diversity leads to differences in pathogenetic mechanisms and hampers HCM therapy. Cardiomyocytes derived from patient-specific induced pluripotent stem cells give new opportunities for studying underlying HCM mechanisms. We generated an iPSC line from peripheral blood mononuclear cells of an HCM patient with a heterozygous p.E510Q mutation in HADHA using non-integrating episomal vectors. The iPSC line showed typical morphology, expression of pluripotency markers, capacity to be differentiated into derivatives of three germ layers, and presence of the patient-specific mutation.
Carotid stenosis is a multidisciplinary problem that requires the involvement of a specialists’ team, including cardiovascular surgeons, neurosurgeons, endovascular surgeons, cardiologists, neurologists, and internists. In this consensus statement, a group of experts considered the main stages of diagnosing carotid stenosis, as well as discussed, the necessary prevention methods and features of choosing the optimal treatment approach. The aim was to provide concise and structured information on the management of patients with carotid stenosis. This document was developed based on the updated clinical guidelines of the European Society for Vascular Surgery and the American Association for Vascular Surgery, taking into account the consensus opinion of Russian experts.
Aim. To study platelet adhesion to a-C:H:SiO x film on titanium in an in vitro experiment to evaluate its antithrombogenic potential. Materials and methods. Thin (less than 1 μm) a-C:H:SiO x films were deposited on VT-6 titanium plates with a size of 10 × 10 mm 2 and a thickness of 0.2 mm using a vacuum ion-plasma unit using pulsed bipolar bias. The surface roughness was evaluated according to GOST 2789-73 using an atomic force microscope. The test samples were cultured at 37 °C for 30 min in platelet-rich human blood plasma, prepared for scanning electron microscopy, after which the distribution density of blood plates adhering to the test coating was calculated. Results. With the same roughness index of the studied a-C:H:SiO x samples, the film decreased 116 times (in comparison with untreated titanium) the platelet count per 1 mm 2 of the surface. Conclusion . The deposition of a-C:H:SiO x thin film on the surface of VT-6 titanium alloy by PACVD method using pulsed bipolar bias significantly reduces the distribution density of platelets in comparison with an untreated metal surface. In vitro data suggest a significant antithrombogenic potential of this type of coating on the surface of devices in contact with blood.
Purpose: Since currently there are no selective drugs for paramagnetic contrast enhancement (PMC) in MRI in the oncology clinic as such, we tried to obtain a selective oncotropic paramagnetic contrast agent (PMCA) – Mn(II) manganese compound with glucaric acid (used in combination with 99mTc for breast cancer (breast cancer), and to evaluate on the basis of animal studies the possibility of using Mn(II)-glucarate (Glucaromang) as an oncotropic PMCA in breast cancer. Material and methods: The synthesis of glucaric acid was carried out by a modified method by oxidation of D-glucose with strong nitric acid. A solution of D-glucaric acid was used to produce manganese glucarate by combining with manganese oxide or carbonate with an excess of glucarate in solution, since one manganese atom forms a complex with two glucaric acid molecules. The injection solution of the obtained Mn(II)-glucarate was adjusted to pH = 6.4–7.2 and sterilized by microfiltration through Millipore filters with a pore size of 0.22 μm. The toxicity indices LD10, LD50, LD90 (ml/kg) were determined in laboratory white mice. An in vivo MRI study of the tumor accumulation of Mn(II)-glucarate was performed in veterinary patients – cats (n = 9) with diagnosed breast cancer, who underwent body MRI to clarify the diagnosis and assess the extent of breast cancer, and 4 cats with malignant tumors of the neck and submandibular region (salivary glands). Scanning was performed using Toshiba Titan Vantage (Canon Medical) and Magnetom Open (Siemens Medical), with subsequent processing by Radiant (https://www.radiantviewer.com ). Results: In the injection solution of Mn(II)-glucarate 0.5 M, free manganese was absent in detectable amounts, the excess of glucaric acid (has an antineoproliferative effect) was up to 2–2.5 %. Osmolality 1550±39 mOsmol/(kg H2O), viscosity 2.85±0.15 MPa·s, at 37 °C. When stored for 6 months, there was no release of manganese from the complex. The thermodynamic stability constant was 17.6–17.9. For the injection drug «Mn(II)-glucarate, 0.5M, aqueous solution”, the mortality rates for single administration in mice were, respectively: LD10 = 6.8 ± 5.0 ml/kg, LD50=15.1 ± 4.7 ml/kg, LD90=37.5 ± 23.8 ml/kg . When administered Mn(II)-glucarate as laboratory mice and cats with breast cancer did not show significant changes in the blood pattern and any side effects. The drug accumulated intensively in the primary tumor and metastases. The index of enhancement for T1-WI was 1.78 ± 0.082 (p < 0.02) for the primary tumor and 1.49 ± 0.09 (p < 0.05) for lymphogenic metastases. Conclusion: Mn-glucarate is an original paramagnetic contrast agent, highly stable, non-toxic, providing in vivo intensive MRI imaging of tumor structures, in particular in breast cancer.
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