Background: Cardiorespiratory fitness plays an important role in coping with hypoxic stress at high altitudes. However, the association of cardiorespiratory fitness with the development of acute mountain sickness (AMS) has not yet been evaluated. Wearable technology devices provide a feasible assessment of cardiorespiratory fitness, which is quantifiable as maximum oxygen consumption (VO2max) and may contribute to AMS prediction. Objective: We aimed to determine the validity of VO2max estimated by the smartwatch test (SWT), which can be self-administered, in order to overcome the limitations of clinical VO2max measurements. We also aimed to evaluate the performance of a VO2max-SWT–based model in predicting susceptibility to AMS. Methods: Both SWT and cardiopulmonary exercise test (CPET) were performed for VO2max measurements in 46 healthy participants at low altitude (300 m) and in 41 of them at high altitude (3900 m). The characteristics of the red blood cells and hemoglobin levels in all the participants were analyzed by routine blood examination before the exercise tests. The Bland-Altman method was used for bias and precision assessment. Multivariate logistic regression was performed to analyze the correlation between AMS and the candidate variables. A receiver operating characteristic curve was used to evaluate the efficacy of VO2max in predicting AMS. Results: VO2max decreased after acute high altitude exposure, as measured by CPET (25.20 [SD 6.46] vs 30.17 [SD 5.01] at low altitude; P<.001) and SWT (26.17 [SD 6.71] vs 31.28 [SD 5.17] at low altitude; P<.001). Both at low and high altitudes, VO2max was slightly overestimated by SWT but had considerable accuracy as the mean absolute percentage error (<7%) and mean absolute error (<2 mL·kg–1·min–1), with a relatively small bias compared with VO2max-CPET. Twenty of the 46 participants developed AMS at 3900 m, and their VO2max was significantly lower than that of those without AMS (CPET: 27.80 [SD 4.55] vs 32.00 [SD 4.64], respectively; P=.004; SWT: 28.00 [IQR 25.25-32.00] vs 32.00 [IQR 30.00-37.00], respectively; P=.001). VO2max-CPET, VO2max-SWT, and red blood cell distribution width-coefficient of variation (RDW-CV) were found to be independent predictors of AMS. To increase the prediction accuracy, we used combination models. The combination of VO2max-SWT and RDW-CV showed the largest area under the curve for all parameters and models, which increased the area under the curve from 0.785 for VO2max-SWT alone to 0.839. Conclusions: Our study demonstrates that the smartwatch device can be a feasible approach for estimating VO2max. In both low and high altitudes, VO2max-SWT showed a systematic bias toward a calibration point, slightly overestimating the proper VO2max when investigated in healthy participants. The SWT-based VO2max at low altitude is an effective indicator of AMS and helps to better identify susceptible individuals following acute high-altitude exposure, particularly by combining the RDW-CV at low altitude. Trial Registration: Chinese Clinical Trial Registry ChiCTR2200059900; https://www.chictr.org.cn/showproj.html?proj=170253

Left atrial appendage (LAA) thrombus detachment resulting in intracranial embolism is a major complication of atrial fibrillation (AF). Endocardial endothelial cell (EEC) injury leads to thrombosis, whereas autophagy protects against EEC dysfunction. However, the role and underlying mechanisms of autophagy in EECs during AF have not been elucidated. In this study, we isolated EECs from AF model mice and observed reduced autophagic flux and intracellular calcium concentrations in EECs from AF mice. In addition, we detected an increased expression of the mechanosensitive protein PLXND1 in the cytomembranes of EECs. PLXND1 served as a scaffold protein to bind with ORAI1 and further decreased ORAI1-mediated calcium influx. The decrease in the calcium influx-mediated phosphorylation of CAMK2 is associated with the inhibition of autophagy, which results in EEC dysfunction in AF. Our study demonstrated that the change in PLXND1 expression contributes to intracellular calcium dyshomeostasis, which inhibits autophagy flux and results in EEC dysfunction in AF. This study provides a potential intervention target for EEC dysfunction to prevent and treat intracardiac thrombosis in AF and its complications.

The dynamic characteristics of cardiorespiratory fitness during high-altitude acclimatization and deacclimatization are not well elucidated, and whether ubiquinol exerts beneficial effects on cardiorespiratory fitness remains debated. In this trial, 41 volunteers were randomized to receive oral ubiquinol or placebo administration, 14 days before departure to highlands. All individuals were carried to 3900 m by air and then returned to 300 m after 7 days. Cardiopulmonary exercise testing was performed at baseline, on the third day after arrival in the highlands, and on the seventh day after return. This trial revealed the dynamic characteristics of cardiorespiratory fitness during the entire high-altitude acclimatization and deacclimatization process. The short-term journey to the highlands did not significantly affect cardiorespiratory fitness or physical performance capacity after the return. Cardiovascular and respiratory recoveries were desynchronized after returning from the highlands. Ubiquinol supplementation maintained the physical performance capacity in the highlands and facilitated acclimatization to hypoxia.

Background and Aims: Ablation for premature ventricular complexes (PVCs) originating from the right ventricular inflow tract (RVIT) is challenging. Few studies have identified the correlation between right ventricular false tendons (RVFTs) and RVIT PVCs. This study aimed to verify RVFTs as arrhythmogenic and electro‐anatomical substrates for PVCs, and propose an enlightening mapping and ablation protocol to improve operative efficacy. Methods: We retrospectively analyzed 63 patients with PVCs originating from the RVIT and six were found to possess arrhythmogenic RVFTs. RVFTs were identified via the intracardiac echocardiography (ICE) imaging as fibrous or fibro‐muscular bands traversing the right ventricle cavity with no connection to valvular cusps. ICE was used to reconstruct the geometry of the right ventricle, and verify the successful ablation target. Moreover, morphological and histological studies of RVFTs from swine hearts were performed to reveal potential arrhythmogenic mechanisms. Results: All RVFTs were found in the free wall of the right ventricle, with a similar connection from the subvalvular myocardium to the free wall, but with different spatial orientations, shapes, lengths, and thicknesses. Reconstruction of three‐dimensional geometry with ICE was of immense benefit in terms of the location of the target spot and successful ablation. Despite variable morphology, the successful target site was consistently located at the subvalvular end of the RVFTs. Morphological and histological analysis of RVFTs from a swine heart demonstrated a component of cardiac muscles and fibrous tissues that may account for triggering activity, such as outflow tract PVCs. Conclusion: RVFTs may serve as arrhythmogenic and electro‐anatomical substrates for RVIT PVCs. The “culprit” RVFTs can be identified and reconstructed in the three‐dimensional system through ICE examinations, which may improve operative efficacy.

Editorial: Autophagy in diseases—From basic to clinic