ABC | Volume 114, Nº2, February 2020

Original Article Gonçalves et al. Prediction of CPET in HF patients with AF Arq Bras Cardiol. 2020; 114(2):209-218 Prospective follow-up included initial evaluation within a period of one month in each patient with: • Clinical data including etiology of HF, implanted devices, medication, comorbidities, NYHA class and Heart Failure Survival Score (HFSS); 9 • Laboratory data; • Electrocardiographic data; • Echocardiographic data; • CPET data. Patients were excluded if one of the following: • Age < 18 years; • Planned percutaneous coronary revascularization or cardiac surgery; • Elective HT in the follow-up period; • Exercise-limiting comorbidities (cerebrovascular disease, musculoskeletal impairment, or severe peripheral vascular disease); • Previous HT. Follow-up and endpoint All patients were followed-up for 12 months from the date of completion of the aforementioned complementary exams. The primary endpoint was a composite of cardiac death or urgent HT (occurring during an unplanned hospitalization with dependency of inotropes for worsening HF). Data were obtained from the outpatient clinic visits and medical charts review and was complemented with a standardized telephone interview to all patients at 12 months of follow-up. Secondary endpoints included all-cause mortality, sudden cardiac death and death for worsening HF. Definition of atrial fibrillation Only persistent or permanent AF was considered for the analysis. The diagnosis was made by electrocardiographic recording in the initial evaluation. Cardiopulmonary exercise testing A maximal symptom-limited treadmill CPET was performed using the modified Bruce protocol (GE Marquette Series 2000 treadmill). Tha gas analysis was preceded by the calibration of the equipment. Minute ventilation, oxygen uptake and carbon dioxide production were acquired breath-by-breath, using a SensorMedics Vmax 229 gas analyser. The pVO 2 was defined as the highest 30-second average achieved during exercise and was normalized for body mass. 10 The anaerobic threshold was determined by combining the standard methods (V-slope preferentially and ventilatory equivalents). The VE/ VCO 2 slope was calculated by least-squares linear regression, using data acquired throughout the whole exercise. Several composite parameters of CPET were also calculated. Patients were encouraged to perform exercise until the respiratory exchange ratio (RER) was ≥1.10. Statistical analysis All analyses compare AF patients with SR patients. Data were analysed using the software Statistical Package for the Social Science for Windows, version 24.0 (SPSS Inc, Chicago IL). Baseline characteristics were summarized as frequencies (percentages) for categorical variables, as means and standard deviations for continuous variables when normality was verified and as median and interquartile range when normality was not verified by the Kolmogorov-Smirnov test. The Student’s t-test for independent samples or the Mann- Whitney test when normality was not verified were used for the analysis of the variables. Univariable and multivariable Cox proportional-hazards models were applied, with p values for time-to-event analyses being based on log-rank tests, and hazard ratios for treatment effects and 95% confidence intervals presented to study the combined endpoint considering the follow-up time of 12 months. For selecting patients who would benefit from early selection for HT or mechanical circulatory support, the primary endpoint was analysed by several CPET parameters for the highest area under the curve (AUC) in the 12 months’ follow- up. Hanley &McNeil test was used to compare two correlated receiver operating characteristics curves. 11 The guideline recommended cut-off value of pVO 2 (pVO 2 ≤ 12 ml/kg/min or ≤ 14 ml/kg/min without beta- blockers (BB)) and VE/VCO 2 slope (VE/VCO 2 slope > 35 with a RER < 1.05) for HT 7 selection were analysed (and compared for positive and negative predictive value (PPV and NPV, respectively) in our population of AF and SR patients. Statistical differences with a p-value < 0.05 were considered significant. Results Overview of AF and SR groups A total of 274 patients were enrolled in the study, with 51 patients in the AF group and 223 in the SR group. The baseline characteristics of SR and AF groups are presented and compared in Table 1. In regard to clinical data, AF patients were older (57.96 ± 8.61 vs 52.61 ± 12.53, p < 0.001) and had a lower percentage of females. Medication with angiotensin- converting enzyme inhibitors, angiotensin receptor blockers, BB and mineralocorticoid receptor antagonists were similar and highly prevalent in both groups, and no differences were found regarding implantable cardioverter-defibrillator and cardiac resynchronization therapy between the two groups. There were no significant differences for sodium and NT- proBNP, but glomerular filtration rate (GFR) values were lower in the AF group (65.03 ± 29.05 vs 76.84 ± 30.20, p = 0.012). Higher percentage of right ventricular dysfunction (40.0% vs 13.0%, p < 0.001) and lower values of LVEF (24.96 ± 7.44 vs 27.91 ± 7.23, p = 0.010), revealed a worse biventricular function in AF group. CPET data showed no differences regarding heart rate parameters, but the AF group had lower baseline and maximal systolic blood pressure (SBP). Significant differences between 210