Safety and efficacy of transitioning from selexipag to oral treprostinil in pulmonary arterial hypertension: Findings from the ADAPT registry.

PURPOSE: Oral treprostinil and selexipag are drugs targeting the prostacyclin pathway and are approved for treatment of pulmonary arterial hypertension (PAH). In the setting of unsatisfactory clinical response or tolerability issues while on selexipag, there is little data on clinical benefit, safety, or strategies on transitioning to oral treprostinil. Using prospective data from the ADAPT registry, we aimed to evaluate clinical outcomes, safety, and transition strategies in ten patients with PAH transitioning from selexipag to oral treprostinil. METHODS: ADAPT was a prospective, real-world, multicenter, United States-based registry of patients with PAH newly started on oral treprostinil, with a cohort of patients (n = 10) transitioning from selexipag to oral treprostinil. PAH variables of interest were collected from standard-of-care clinic visits. Clinical improvement was defined by modified REPLACE criterion, and risk was assessed by REVEAL Lite 2 from baseline to last follow-up. Real world transition strategies were recorded. Healthcare utilization or worsening PAH was evaluated within 30 days of transitions. RESULTS: Seven patients transitioned due to worsening PAH or lack of efficacy on selexipag, and three patients transitioned due to tolerability issues. Based on the modified REPLACE criterion, five patients demonstrated clinical improvement after transition from selexipag to oral treprostinil. Using REVEAL Lite 2 to assess risk, three patients improved and five patients maintained risk category from baseline to last follow-up. All transitions occurred in an outpatient setting either as abrupt stop/start or cross-titration, without parenteral treprostinil bridging. CONCLUSION: Transition from selexipag to oral treprostinil was safe, performed without parenteral prostacyclin bridging, and resulted in clinical and categorical risk improvements in some patients.

[Atherosclerotic heart defects]. / Ateroskleroticheskie poroki serdtsa.

Clinical, echocardiographic, Doppler echocardiographic, electro- and phonocardiographic studies were performed in 31 patients with cardiac atherosclerotic lesions (aortic in 17 patients, aortomitral in 10, mitral in 4) and in 20 patients matched for age, sex, and underlying abnormality, but without cardiac disease. Atherosclerotic defects caused by calcification of the valvular apparatus were shown to be rarely (5.9% of patients) isolated, they were more frequently combined or concurrent. Atherosclerotic defects caused no significant myocardial structural and functional changes in addition to the underlying pathology. Aortic atherosclerotic stenosis is diagnosed at equal rates by using echo and phonocardiography, whereas aortic valvular insufficiency and mitral diseases are better (7- and 9-fold) detected with echocardiography and Doppler echocardiography, whereas aortic valvular insufficiency and mitral diseases are better (7- and 9-fold) detected with echocardiography and Doppler echocardiography than with phonocardiography.

[Valvular prolapse (clinical, echocardiographic, phonocardiographic and electrocardiographic features)]. / Prolapsy klapanov (klinicheskaia, ékhokardiograficheskaia, fonokardiograficheskaia i élektrokardiograficheskaia kharakteristiki).

Clinical, echoCG, PCG and ECG examinations were performed in 42 patients with primary isolated valve prolapses: mitral, aortal and tricuspid (32, 5 and 5 patients, respectively). It is shown that degree 1 regurgitation caused no hemodynamic disturbances, that of degree 2 and 3 brought about cardial complaints in more than half the patients, hemodynamic overstrain of the heart, sound symptoms similar to those of relevant valvular disease.

[Status of the internal organs in nephrotic syndrome]. / Sostoianie vnutrennikh organov pri nefroticheskom sindrome.

As a result of clinical and experimental observations the authors have established that even at the early stages of the nephrotic syndrome there occur myocardial lesions determined by concomitant impairment of microcirculation and metabolism leading to the development of nephrotic cardiomyopathy. The appearance of the nephrotic syndrome may be accompanied by the development of hydrothorax and more seldom, primarily in acute glomerulonephritis, by nephrogenous edema of the lungs. The nephrotic syndrome does not exert any material effect on the changes in external respiratory function, common to glomerulonephritis. Nephrotic gastropathy is of total character with low magnitudes of acid secretion and intragastric proteolysis. This does not create any conditions for acid-peptic damage to the gastroduodenal mucosa attended by ulcer formation.

[Changes in the myocardium in the early stages of chronic kidney failure]. / Izmeneniia v miokarde na rannikh stadiiakh khronicheskoi pochechnoi nedostatochnosti.

The functional state of the myocardium was studied in 45 white Wistar rats in the early stages of chronic renal insufficiency. After resection of 4/6 of the renal parenchyma the initial stage of chronic renal insufficiency was created with the urea level in blood serum 7.0-10.0 mmol/l with normal content of electrolytes (duration of observation lasting 1.3 to 6 months). Towards the 3rd month myocardial hypertrophy developed in animals with statistically significant increase of the cardiac mass by 18-20%, not related to enhancement of haemodynamic load on the heart. Arterial pressure remains normal. Hypertrophy of the myocardium as shown by histochemistry was accompanied by increase of energy and protein metabolism, carbohydrates decreased simultaneously due to the decrease of myocardium tolerance to glucose.