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Abstract: Pulmonary arterial hypertension (PAH) is a severe and progressive disease with limited survival prospects under currently available therapies. Since the 2022 edition of the European Society of Cardiology and European Respiratory Society guidelines on pulmonary hypertension, substantial clinical evidence has emerged, supporting a new treatment algorithm for PAH as presented at the 7th World Symposium on Pulmonary Hypertension 2024 and the following proceeding papers. Key updates include the introduction of sotatercept as a second-line therapy leading to a revised definition of maximal medical therapy now encompassing agents from four therapeutic groups (phosphodiesterase-5 inhibitors/soluble guanylate cyclase stimulators, endothelin receptor antagonists, prostacyclin pathway agents, and sotatercept), instead of three (phosphodiesterase-5 inhibitors/soluble guanylate cyclase stimulators, endothelin receptor antagonists, prostacyclin pathway agents). Other novelties include the elimination of a distinct pathway for patients with cardiopulmonary comorbidities in favor of an individualized approach, a reduction in the initial patient assessment risk categories from three to two, and a follow-up interval shortened from 3–6 months to 3–4 months post-treatment initiation. This review presents these advancements and emphasizes the need for their widespread implementation in clinical practice. At the end, we present new opportunities and challenges in the treatment of pulmonary arterial hypertension in eight Central and Eastern European countries.
Keywords: activin signaling inhibitors, novel therapies, risk assessment, treatment strategy, sotatercept
Published in DiRROS: 15.12.2025; Views: 44; Downloads: 19
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Abstract: The aim of the open label extension (OLE) of CTREPH study was to characterize multimodal treatment in patients with severe inoperable CTEPH, to describe long-term subcutaneous (SC) treprostinil safety and tolerability, and to evaluate change in functional class and exercise capacity over 24 months since completion of the blinded phase of CTREPH. The target population in the OLE consisted of patients who completed 24 weeks of blinded treatment with either high-dose treprostinil of around 30 ng/kg/min (former high-dose group), or low-dose treprostinil of around 3 ng/kg/min (former low-dose group) in the CTREPH study. From the start of OLE, treprostinil dose and any additional therapy were chosen according to the standard of care and physician's discretion. Out of 47 enrolled patients, 20 patients received other PH drugs during OLE and 17 patients underwent at least 1 BPA session. Number of treprostinil-related AEs was substantially higher in the former low-dose group in comparison to the former high-dose group. Related AEs were also more frequent during the first 6 months of the preceding blinded trial than over 24 months of OLE, especially infusion site pain and all local infusion site reactions. No new safety signal was detected. Evaluated clinical outcomes show sustained benefit from long-term treprostinil treatment. Long-term SC treprostinil is a safe and effective component of multimodal treatment for patients with severe CTEPH. Patients who tolerate treprostinil after initiation are likely to continue tolerating it over time, with the clinical benefit maintained over 24 months.
Keywords: chronic thromboembolic pulmonary hypertension, multimodal treatment, subcutaneous treprostinil
Published in DiRROS: 15.12.2025; Views: 44; Downloads: 20
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Abstract: Background/Objectives: Sodium glucose co-transporter 2 inhibitors (SGLT2is) improve outcomes in heart failure; however, data in left ventricular non-compaction cardiomyopathy (LVNC) patients are limited. We sought to analyze the clinical effects of the SGLT2is dapagliflozin and empagliflozin in patients with LVNC. Methods: Thirty consecutive LVNC patients diagnosed by CMR were prospectively enrolled. Clinical, biochemical and echocardiography data were obtained at the initiation of the SGLT2is and at the 12-month follow-up. All patients were on stable guideline-directed medical therapy. A response to SGLT2i therapy was defined as an improvement in LVEF ≥ 5% at 12 months. Results: Of the 30 enrolled patients, 25 were male, with a mean age of 49 ± 16 years and few comorbidities. Dapagliflozin 10 mg was prescribed to 23 patients and empagliflozin 10 mg to 7 patients. Five patients experiened an adverse event during follow-up (one sudden cardiac death; four heart transplantations or LVAD implantations). During follow-up, significant improvements were observed in LVEF (32.1 ± 6.9% vs. 43.5 ± 9.7%; p = 0.003), LVOT VTI (14.8 ± 6.5 cm vs. 17.6 ± 3.3 cm; p = 0.008), E/e′ (14.8 ± 4.7 vs. 10.0 ± 4.1; p < 0.001), and TAPSE (2.0 ± 0.4 cm vs. 2.3 ± 0.4 cm; p = 0.012). NT-proBNP levels decreased significantly (2025 ± 2198 pg/mL vs. 582 ± 803 pg/mL; p = 0.005). Eighteen patients responded favorably to SGLT2i therapy (Group A), whereas seven showed no significant LVEF improvement (Group B). The groups did not differ significantly in age, sex, baseline creatinine, or bilirubin. Compared to Group B, Group A had a smaller baseline LV end-diastolic diameter (6.3 ± 0.8 cm vs. 7.1 ± 0.9 cm; p = 0.025) and lower NT-proBNP levels (1720 ± 1662 pg/mL vs. 4527 ± 4397 pg/mL; p = 0.02). Conclusions: In patients with LVNC, SGLT2i therapy is associated with significant reverse remodeling and functional improvement. Benefits may be greater in those with less advanced disease.
Keywords: non-compaction cardiomyopathy, guideline-directed heart failure medical therapy, myocardial recovery
Published in DiRROS: 15.12.2025; Views: 37; Downloads: 19
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Keywords: vsebnost vitaminov pri ljudeh, vitamin D, vpliv pomanjkanja na respiratorna obolenja, priporočila
Published in DiRROS: 15.12.2025; Views: 25; Downloads: 12
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Abstract: Methylmercury (MeHg) represents the most toxic form of mercury, owing to its ability to permeate both the blood-brain and placental barriers, leading to bioaccumulation in organisms. In the marine food web, MeHg concentrations can reach levels millions of times higher than those found in the surrounding environment, posing significant ecological and human health risks. This review provides a comprehensive overviews and critical evaluation of the available biosensor detection platforms for the detection of MeHg, with a focus on their performance based on key parameters such as (i) sensitivity, (ii) selectivity, (iii) response time, and (iv) adaptability to diverse environmental matrices. We examine recent advancements in MeHg biosensing technologies, emphasizing innovative approaches that surpass current methodologies regarding detection limits, reversibility, response time, and operational stability. Furthermore, we present an in-depth discussion on future directions for the development of in situ MeHg detection platforms, with potential applications in both biomedical and environmental monitoring. The review concludes by outlining the challenges and opportunities for advancing MeHg sensing technologies to enhance real-time detection in aqueous environments.
Published in DiRROS: 15.12.2025; Views: 13; Downloads: 5
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