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 Table 6 – Univariate Cox analysis for the primary outcome of the two recommended cardiopulmonary exercise test cut-offs for Heart Transplantation selection SR AF Hazard ratio 95% CI p Hazard ratio 95% CI p pVO 2 ≤ 12 ml/kg/min 8.673 3.048-24.680 < 0.001 44.220 8.686-225.129 < 0.001 VE/VCO 2 slope > 35 20.858 5.985-72.696 < 0.001 5.613 1.164-27.059 0.032 SR: sinus rhythm; AF: atrial fibrillation; CI: confidence interval; pVO 2 : peak O 2 consumption. Table 7 – Proportion of patients correctely classified at 12 months of follow up AF SR pVO 2 ≤ 12 ml/kg/min or ≤ 14 ml/kg/min without BB2 7/7 - 100% 5/13 - 38.5% pVO 2 > 12 ml/kg/min or > 14 ml/ kg/min without BB 42/44 - 95.5% 198/210 - 94.3% pVO 2 ≤ 12 ml/kg/min only in patients doing BB 5/5 - 100% 6/8 - 75% pVO 2 > 12 ml/kg/min only in patients doing BB 34/35 - 97.1% 161/169 - 95.3% VE/VCO 2 slope > 35 7/21 - 33.3% 14/47 - 29.8% VE/VCO 2 slope ≤ 35 28/30 - 92.3% 173/176 - 98.3% SR: sinus rhythm; AF: atrial fibrillation; pVO 2 : peak O 2 consumption; BB: beta-blockers. and when compared with the VE/VCO 2 slope (p = 0.503 and p = 0.701, for SR and AF group respectively). Cut-off value for HT selection: PPV and NPV for the primary outcome The univariate Cox analysis for the primary outcome of the two recommended CPET cut-offs for HT selection 7 (pVO 2 ≤ 12 ml/kg/min or ≤ 14 ml/kg/min without BB and VE/VCO 2 slope ≤ 35) is represented in Table 6, showing that in the two groups, both cut-offs remained predictors of the outcome. In pVO 2 ≤ 12 ml/kg/min or ≤ 14 ml/kg/min without BB, the PPV for the primary outcome was 100% in the AF group and 38.5% in the SR group (Table 7), with a NPV of 95.5% and 94.3% in the AF and SR groups, respectively. Higher values were found when the analysis excluded patients not doing BB, with a PPV of 100% and 75%, and a NPV of 97.1% and 95.3% for the AF and RS groups respectively. In VE/VCO 2 slope > 35 (Table 7), lower values of PPV were reported (33.3% and 29.8% for AF and SR groups, respectively), with similar NPV to pVO 2 (92.3% and 98.3% for AF and SR groups, respectively). Discussion The presence of AF is associated with a negative prognostic effect in HF, with 50-90% increased mortality and HF progression in the Framingham Heart Study. 12 Our population revealed some baseline differences between SR and AF groups, with some of that in previously described prognostic markers of HF, as AF patients were older, 13,14 with lower GFR, 15-17 with worse right ventricular function 18 and a lower LVEF. 19,20 In regard to CPET parameters, our AF patients revealed a lower exercise capacity than SR patients since they had a higher VE/VCO 2 slope and a lower CPET duration, pVO 2 , OUES, time to AT and pVO 2 at AT. As expected, these differences converted in a worse prognosis in the AF group, with a 2-fold increase in the primary endpoint events (17.6% VS 8.1%, p = 0.038) and 3-fold increase in all-cause mortality (17.6% VS 6.3%, p = 0.008) in the 1-year follow-up. The majority of the predictors of the primary endpoint were predictors for both SR and AF groups. The HFSS, 21 Sodium, 22 NT-proBNP, 23-25 right ventricular dysfunction, 18 lower LVEF, 19,20 CPET duration, HHR1, 26 and initial and maximal SBP during CPET 27 were included in this group, with all of them being formerly described as prognostic markers in HF patients. Differences were found regarding maximal HR and variation of HR during the exercise, with lower values in AF patients predicting the primary outcome only in that group. Patients not using BB were solely predictive of the primary outcome in the SR group, but not in the AF group. Whether this is in agreement with other studies that failed to reveal prognostic benefit from BB in the AF group of HF patients 28-30 or to a underpowered analysis since only 11 patients in the AF group were not doing BB cannot be guaranteed. Cut-off value for HT selection: PPV and NPV for the primary outcome Whether HF patients with AF can be precisely stratified with the current CPET cut-offs for HT selection have not been specifically studied before. The cut-off value for pVO 2 showed a PPV for the primary outcome of 100% in the AF group and 38.5% in the SR group, with a NPV of 95.5% and 94.3% in the AF and SR groups, respectively. Hence, despite AF carries a worse prognosis in HF patients, the current cut-off of pVO 2 for HT selection can precisely stratified these high-risk patients, with no patients under the cut-off misdiagnosed as high risk patients and less than 5% of patients above the cut-off having the primary outcome in the 1-year follow-up (Figure 1). These results suggest that patients under the cut-off of pVO 2 should be managed accordingly, considering quickly referring for HT or mechanical circulatory support, since medical treatment is associated with negative outcomes in a 1-year period, and that we can be relatively safe in regard to 1-year outcomes of patients above the cut-off. 214