OBJECTIVES: This study sought to evaluate the safety and efficacy of ninerafaxstat in nHCM.
METHODS: Patients with hypertrophic cardiomyopathy and left ventricular outflow tract gradient <30 mm Hg, ejection fraction ≥50%, and peak oxygen consumption <80% predicted were randomized to ninerafaxstat 200 mg twice daily or placebo (1:1) for 12 weeks. The primary endpoint was safety and tolerability, with efficacy outcomes also assessed as secondary endpoints.
RESULTS: A total of 67 patients with nHCM were enrolled at 12 centers (57 ± 11.8 years of age; 55% women). Serious adverse events occurred in 11.8% (n = 4 of 34) in the ninerafaxstat group and 6.1% (n = 2 of 33) of patients in the placebo group. From baseline to 12 weeks, ninerafaxstat was associated with significantly better VE/Vco2 (ventilatory efficiency) slope compared with placebo with a least-squares (LS) mean difference between the groups of -2.1 (95% CI: -3.6 to -0.6; P = 0.006), with no significant difference in peak VO2 (P = 0.90). The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score was directionally, though not significantly, improved with ninerafaxstat vs placebo (LS mean 3.2; 95% CI: -2.9 to 9.2; P = 0.30); however, it was statistically significant when analyzed post hoc in the 35 patients with baseline Kansas City Cardiomyopathy Questionnaire Clinical Summary Score ≤80 (LS mean 9.4; 95% CI: 0.3-18.5; P = 0.04).
CONCLUSIONS: In symptomatic nHCM, novel drug therapy targeting myocardial energetics was safe and well tolerated and associated with better exercise performance and health status among those most symptomatically limited. The findings support assessing ninerafaxstat in a phase 3 study.
OBJECTIVE: Our aim was to systematically review the scientific literature to identify factors related to the performance of elite sprint cross-country skiers.
METHODS: Four electronic databases were searched using relevant medical subject headings and keywords, as were reference lists, relevant journals, and key authors in the field. Only original research articles addressing physiology, biomechanics, anthropometry, or neuromuscular characteristics and elite sprint cross-country skiers and performance outcomes were included. All articles meeting inclusion criteria were quality assessed. Data were extracted from each article using a standardized form and subsequently summarized.
RESULTS: Thirty-one articles met the criteria for inclusion, were reviewed, and scored an average of 66 ± 7 % (range 56-78 %) upon quality assessment. All articles except for two were quasi-experimental, and only one had a fully-experimental research design. In total, articles comprised 567 subjects (74 % male), with only nine articles explicitly reporting their skiers' sprint International Skiing Federation points (weighted mean 116 ± 78). A similar number of articles addressed skating and classical techniques, with more than half of the investigations involving roller-skiing assessments under laboratory conditions. A range of physiological, biomechanical, anthropometric, and neuromuscular characteristics was reported to relate to sprint skiing performance. Both aerobic and anaerobic capacities are important qualities, with the anaerobic system suggested to contribute more to the performance during the first of repeated heats; and the aerobic system during subsequent heats. A capacity for high speed in all the following instances is important for the performance of sprint cross-country skiers: at the start of the race, at any given point when required (e.g., when being challenged by a competitor), and in the final section of each heat. Although high skiing speed is suggested to rely primarily on high cycle rates, longer cycle lengths are commonly observed in faster skiers. In addition, faster skiers rely on different technical strategies when approaching peak speeds, employ more effective techniques, and use better coordinated movements to optimize generation of propulsive force from the resultant ski and pole forces. Strong uphill technique is critical to race performance since uphill segments are the most influential on race outcomes. A certain strength level is required, although more does not necessarily translate to superior sprint skiing performance, and sufficient strength-endurance capacities are also of importance to minimize the impact and accumulation of fatigue during repeated heats. Lastly, higher lean mass does appear to benefit sprint skiers' performance, with no clear advantage conferred via body height and mass.
LIMITATIONS: Generalization of findings from one study to the next is challenging considering the array of experimental tasks, variables defining performance, fundamental differences between skiing techniques, and evolution of sprint skiing competitions. Although laboratory-based measures can effectively assess on-snow skiing performance, conclusions drawn from roller-skiing investigations might not fully apply to on-snow skiing performance. A low number of subjects were females (only 17 %), warranting further studies to better understand this population. Lastly, more training studies involving high-level elite sprint skiers and investigations pertaining to the ability of skiers to maintain high-sprint speeds at the end of races are recommended to assist in understanding and improving high-level sprint skiing performance, and resilience to fatigue.
CONCLUSIONS: Successful sprint cross-country skiing involves well-developed aerobic and anaerobic capacities, high speed abilities, effective biomechanical techniques, and the ability to develop high forces rapidly. A certain level of strength is required, particularly ski-specific strength, as well as the ability to withstand fatigue across the repeated heats of sprint races. Cross-country sprint skiing is demonstrably a demanding and complex sport, where high-performance skiers need to simultaneously address physiological, biomechanical, anthropometric, and neuromuscular aspects to ensure success.
AIM: This study aims to determine the use of one of three physical performance tests (2-minute step, 2-minute walk, and 1-minute sit to stand) to effectively estimate cardiorespiratory fitness among older adults with CF.
METHODS: In this cross-sectional study, community-dwelling individuals aged 60 years old and above in Klang Valley were screened for CF. The participants performed three physical performance tests (2-minute walk, 2-minute step, and 1-minute sit to stand) followed by treadmill-based maximal exercise testing on another day.
RESULTS: A total of 32 older adults with cognitive frailty (mean age; SD: 67.1;4.7 years) participated in this study. Nearly half of them had hypertension (43.5 %), hypercholesterolemia (43.5 %), and multimorbidity (47.8 %). Among the endurance tests performed, only the 2-minute walk test independently predicted VO2 max by sex-specific with men (R2 = 0.58, p = 0.03) and women (R2 = 0.34, p = 0.01). The 2-minute walk test had good agreement with VO2 max (ICC = 0.77, 95 % CI: -3.1-2.4).
CONCLUSION: The 2-minute walk test is a valid tool for estimating cardiorespiratory fitness among older adults with CF. However, it should be further tested across a larger population.