Mechanical power output is a key performance-determining variable in many cyclic sports. In rowing, instantaneous power output is commonly determined as the dot product of handle force moment and oar angular velocity. The aim of this study was to show that this commonly used proxy is theoretically flawed and to provide an indication of the magnitude of the error. To obtain a consistent dataset, simulations were performed using a previously proposed forward dynamical model. Inputs were previously recorded rower kinematics and horizontal oar angle, at 20 and 32 strokes∙min−1. From simulation outputs, true power output and power output according to the common proxy were calculated. The error when using the common proxy was quantified as the difference between the average power output according to the proxy and the true average power output (P̅residual), and as the ratio of this difference to the true average power output (ratiores./rower). At stroke rate 20, P̅residual was 27.4 W and ratiores./rower was 0.143; at stroke rate 32, P̅residual was 44.3 W and ratiores./rower was 0.142. Power output in rowing appears to be underestimated when calculated according to the common proxy. Simulations suggest this error to be at least 10% of the true power output.
AimsGenetic hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere protein-encoding genes (i.e. genotype-positive HCM). In an increasing number of patients, HCM occurs in the absence of a mutation (i.e. genotype-negative HCM). Mitochondrial dysfunction is thought to be a key driver of pathological remodelling in HCM. Reports of mitochondrial respiratory function and specific disease-modifying treatment options in patients with HCM are scarce.Methods and resultsRespirometry was performed on septal myectomy tissue from patients with HCM (n = 59) to evaluate oxidative phosphorylation and fatty acid oxidation. Mitochondrial dysfunction was most notably reflected by impaired NADH-linked respiration. In genotype-negative patients, but not genotype-positive patients, NADH-linked respiration was markedly depressed in patients with an indexed septal thickness ≥10 compared with <10. Mitochondrial dysfunction was not explained by reduced abundance or fragmentation of mitochondria, as evaluated by transmission electron microscopy. Rather, improper organization of mitochondria relative to myofibrils (expressed as a percentage of disorganized mitochondria) was strongly associated with mitochondrial dysfunction. Pre-incubation with the cardiolipin-stabilizing drug elamipretide and raising mitochondrial NAD+ levels both boosted NADH-linked respiration.ConclusionMitochondrial dysfunction is explained by cardiomyocyte architecture disruption and is linked to septal hypertrophy in genotype-negative HCM. Despite severe myocardial remodelling mitochondria were responsive to treatments aimed at restoring respiratory function, eliciting the mitochondria as a drug target to prevent and ameliorate cardiac disease in HCM. Mitochondria-targeting therapy may particularly benefit genotype-negative patients with HCM, given the tight link between mitochondrial impairment and septal thickening in this subpopulation.
