Development and validation of clinical prediction models for cardiorespiratory fitness in atrial fibrillation patients following radiofrequency catheter ablation

BackgroundAssessment of cardiorespiratory fitness (CRF) is imperative in patients with atrial fibrillation (AF) who have had radiofrequency catheter ablation (RFCA). This study aimed to develop and validate CRF prediction models in this population.Methods141 AF patients with RFCA were recruited. The cardiopulmonary exercise test was used to assess CRF with VO2peak and METsmax. Multidimensional predictors (demographics, serum biomarkers, cardiovascular parameters, and motor function parameters) were analyzed through Spearman correlation analysis and stepwise multivariate linear regression analysis. The internal validity of the prediction equation was tested by paired Student's t-test, Pearson correlation analysis and Bland-Altman analysis.ResultsSex, BMI, ln NT-proBNP, glucose (GLU), 6-minute walking distance (6MWD), and systolic blood pressure (SBP) were found to be significantly associated with CRF in this population. Multivariate linear regression generated the equations: VO2peak = 35.080 − 0.286 * BMI − 1.927 * Sex − 1.090 * ln NT-proBNP + 0.011 * 6MWD − 0.039 * SBP − 0.512 * GLU, and METsmax = 9.646 − 0.447 * Sex − 0.260 * ln NT-proBNP − 0.140 * GLU − 0.078 * BMI − 0.016 * SBP + 0.004 * 6MWD, (VO2peak: adjusted R2 = 0.506, and METsmax: adjusted R2 = 0.469, both P < 0.01). Pearson correlations between the predicted values and the measured values showed good validity (VO2peak: r = 0.616, and METsmax: r = 0.581, both P < 0.01). The Bland-Altman analysis showed that the predicted VO2peak values were slightly lower than the measured values (mean difference = −0.13; 95% limits of agreement: −5.20 to 4.93), while the predicted METsmax values were in close agreement with the measured values (mean difference = −0.00; 95% limits of agreement: −1.59 to 1.59).ConclusionSex, BMI, NT-proBNP, glucose, 6MWD, and SBP are robust predictors of VO2peak and METsmax in AF population after RFCA. This study generates and internal validates the first multivariable CRF prediction models with easy-to use clinical paraments in AF patients after RFCA, thereby providing safe and effective alternatives to conventional CPX, which may help to optimize personalized patient management

CPNE5 overexpression inhibits cardiomyocytes apoptosis by promoting the degradation of FAS receptor

Summary: CPNE5, a member of the Copine family, is characterized by its membrane-binding properties and functions as a regulatory modulator of intracellular signaling through the spatial redistribution of interacting protein partners. Emerging evidence has demonstrated that CPNE3 exerts cardioprotective effects via anti-apoptotic activity in myocardial ischemia-reperfusion injury models. However, the functional role of CPNE5 in cardiac pathology remains unclear. In this study, the cardiac-specific overexpression of CPNE5 in mice improved cardiac function, reduced cellular apoptosis, and attenuated cardiac fibrosis in both transverse aortic constriction and ischemia-reperfusion models. Conversely, CPNE5 knockout mice exhibited opposite pathological phenotypes. Mechanistic studies revealed that CPNE5 retains FAS within the endoplasmic reticulum and promotes its degradation through the ER-phagy pathway. This process involves CPNE5’s interaction with the autophagy marker LC3 and CALCOCO1, a key receptor in the ER-lysosome-associated degradation (ERLAD) pathway. Collectively, these findings indicate that CPNE5 overexpression protects cardiomyocytes against FASL-induced apoptosis under stress and ischemic conditions