RESUMEN
Importance: Mavacamten, a cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the EXPLORER-HCM study. However, the full extent of mavacamten's effects on exercise performance remains unclear. Objective: To investigate the effect of mavacamten on exercise physiology using cardiopulmonary exercise testing (CPET). Design, Setting, and Participants: Exploratory analyses of the data from the EXPLORER-HCM study, a randomized, double-blind, placebo-controlled, phase 3 trial that was conducted in 68 cardiovascular centers in 13 countries. In total, 251 patients with symptomatic obstructive HCM were enrolled. Interventions: Patients were randomly assigned in a 1:1 ratio to mavacamten or placebo. Main Outcomes and Measures: The following prespecified exploratory cardiovascular and performance parameters were assessed with a standardized treadmill or bicycle ergometer test protocol at baseline and week 30: carbon dioxide output (VCO2), minute ventilation (VE), peak VE/VCO2 ratio, ventilatory efficiency (VE/VCO2 slope), peak respiratory exchange ratio (RER), peak circulatory power, ventilatory power, ventilatory threshold, peak metabolic equivalents (METs), peak exercise time, partial pressure of end-tidal carbon dioxide (PETCO2), and VO2/workload slope. Results: Two hundred fifty-one patients were enrolled. The mean (SD) age was 58.5 (11.9) years and 59% of patients were male. There were significant improvements with mavacamten vs placebo in the following peak-exercise CPET parameters: peak VE/VCO2 ratio (least squares [LS] mean difference, -2.2; 95% CI, -3.05 to -1.26; P < .001), peak METs (LS mean difference, 0.4; 95% CI, 0.17-0.60; P < .001), peak circulatory power (LS mean difference, 372.9 mL/kg/min × mm Hg; 95% CI, 153.12-592.61; P = .001), and peak PETCO2 (LS mean difference, 2.0 mm Hg; 95% CI, 1.12-2.79; P < .001). Mavacamten also improved peak exercise time compared with placebo (LS mean difference, 0.7 minutes; 95% CI, 0.13-1.24; P = .02). There was a significant improvement in nonpeak-exercise CPET parameters, such as VE/VCO2 slope (LS mean difference, -2.6; 95% CI, -3.58 to -1.52; P < .001) and ventilatory power (LS mean difference, 0.6 mm Hg; 95% CI, 0.29-0.90; P < .001) favoring mavacamten vs placebo. Conclusions and Relevance: Mavacamten improved a range of CPET parameters beyond pVO2, indicating consistent and broad benefits on maximal exercise capacity. Although improvements in peak-exercise CPET parameters are clinically meaningful, the favorable effects of mavacamten on submaximal exertional tolerance provide further insights into the beneficial impact of mavacamten in patients with obstructive HCM. Trial Registration: ClinicalTrials.gov Identifier: NCT03470545.
Asunto(s)
Cardiomiopatía Hipertrófica , Prueba de Esfuerzo , Humanos , Masculino , Persona de Mediana Edad , Femenino , Dióxido de Carbono/uso terapéutico , Consumo de Oxígeno/fisiologíaRESUMEN
Carbon nanofibers having interesting smooth, spherical beads are synthesized using a catalyst assisted vapor phase process under various methane/hydrogen mixtures. Fe(1-x)S(x) powders were used as the catalyst. The synthesis temperatures were 1100 degrees C and 1200 degrees C, which are lower than the ones used previously for the formation of beaded carbon nanofibers or nanotubes. Unlike the high temperature (> or = 1300 degrees C) grown beads that may exhibit a rough surface, all the beads obtained at both 1100 and 1200 degrees C with various methane concentrations have a smooth surface. The diameter and the linear density (no. of beads per unit fiber length) of the beads do not seem to correlate to the growth temperature and the methane concentration. The linear density is also independent of the growth time. However, the beads grow with time. Although the grown mechanism is not clear at the present time, it seems that a three-dimensional nucleation model plays a role.