Prognostic Value of Cardiopulmonary Exercise Testing in Patients with Atrial Fibrillation Hidekazu Tsuneoka 1)2), Akira Koike 2), Osamu Nagayama 2), Koji Sakurada 2), Hitoshi Sawada 2), Kazutaka Aonuma 1), Tadanori Aizawa 2) 1) Cardiovascular Division, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan 2) The Cardiovascular Institute, Tokyo, Japan Conflict of interest: None declared
Background It is well known that the parameters obtained from cardiopulmonary exercise testing (CPX) are valuable to predict prognosis in cardiac patients. However, there are few reports on the value of CPX parameters for predicting future cardiac events in patients with persistent atrial fibrillation (AF). Objective The aim of this study is to compare the prognostic value of CPX parameters between patients with sinus rhythm (SR) and those with persistent atrial fibrillation (AF).
Subjects A total of 550 consecutive patients with organic heart disease who underwent CPX from February, 2001 to August, 2003 for evaluation of exercise capacity at the Cardiovascular Institute. Persistent atrial fibrillation which was defined as atrial fibrillation that continued more than 7 days was subject of this study. Patients with lone AF or paroxysmal AF were excluded from this study.
CPX An incremental symptom-limited exercise test was performed using a cycle ergometer. Peak VO2, ΔVO2/ΔWR and VE-VCO2 slope were measured using an AE-300S Respiromonitor (MINATO Medical Science; Osaka, Japan). Echocardiography Left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs), and left ventricular ejection fraction (LVEF) were measured by echocardiography.
Clinical characteristics of the subjects with sinus rhythm (SR) and those with persistent atrial fibrillation (AF) Variable All patients Patients Patients with SR with AF (n=550) (n=478) (n=72) p value Male 434 (78.9%) 387 (81.0%) 47 (62.3%) <0.005 Age, year 63.4 ± 10.5 63.2 ± 10.8 64.3 ± 8.2 NS BMI, kg/m2 23.2 ± 3.2 23.3 ± 3.2 22.4 ± 3.2 <0.05 Etiology CAD 335 (60.9%) 323 (67.6%) 12 (16.7%) <0.001 VD 161 (29.3%) 111 (23.2%) 50 (69.4%) <0.001 DCM 35 (6.4%) 27 (5.6%) 8 (11.1%) NS HCM 19 (3.5%) 17 (3.6%) 2 (2.8%) NS Echocardiography LVDd, mm 51.1 ± 8.4 50.7 ± 8.2 53.9 ± 9.2 <0.005 LVDs, mm 35.2 ± 10.6 34.5 ± 10.4 39.2 ± 11.3 <0.001 LVEF, % 59.2 ± 15.5 60.0 ± 15.3 53.8 ± 15.4 <0.005 Parameters from CPX Peak VO2, ml/min/kg 18.3 ± 5.4 18.8 ± 5.2 14.8 ± 4.9 <0.0001 ΔVO2/ΔWR, ml/kg/w 9.1 ± 2.2 9.4 ± 2.0 7.4 ± 3.0 <0.0001 VE-VCO2 slope 32.6 ± 8.1 31.8 ± 6.9 38.0 ± 12.1 <0.0001 HR at peak, bpm 128.5 ± 23.9 126.5 ± 20.9 141.9 ± 35.7 <0.0001
Endpoint The follow-up period is 1199 ± 546 days. Primary endpoint Death due to worsening of heart failure Sudden cardiac death Death due to acute myocardial infarction Secondary endpoint* Worsening of heart failure requiring hospitalization Worsening of angina pectoris requiring hospitalization New acute myocardial infarction Cardiac death *Only the first event in each patient was counted
Comparisons of Cardiac Events Between Patients with SR and those with AF All patients Patients with SR (n=550) (n=478) (n=72) Patients with AF p value Primary endpoint 15 (2.7) 9 (1.9) 6 (8.3) <0.01 Death due to worsening of heart failure 9 (1.6) 5 (1.0) 4 (5.6) <0.05 Sudden cardiac death 5 (1.0) 3 (0.6) 2 (2.8) NS Death due to acute myocardial infarction 1 (0.2) 1 (0.2) 0 (0.0) NS Secondary endpoint * 121 (22.0) 96 (20.1) 25 (34.7) <0.01 Hospitalization due to worsening of heart failure 64 (11.6) 45 (9.4) 19 (26.4) <0.001 Hospitalization due to worsening of angina pectoris 48 (8.7) 47 (9.8) 1 (1.4) <0.05 Acute myocardial infarction 1 (0.2) 1 (0.2) 0 (0.0) NS Cardiac death 8 (1.5) 3 (0.6) 5 (7.0) <0.005 ( );%, * Only the first event in each patient was counted.
Cox proportional hazards analysis of cardiac deaths (primary endpoint) in patients with SR Univariate Analysis Multivariate Analysis Variables χ2 p value HR 95% CI χ2 p value HR 95% CI Age 0.964 0.3262 1.035 0.966-1.110 0.022 0.8825 1.006 0.933-1.084 Gender 0.093 0.7604 0.783 0.163-3.771 0.003 0.9575 0.950 0.146-6.187 BMI 2.739 0.0981 0.831 0.668-1.035 1.700 0.1922 0.829 0.629-1.099 Peak VO2 16.269 <0.0001 0.728 0.625-0.850 5.016 0.0251 0.648 0.443-0.947 ΔVO2/ΔWR 18.864 <0.0001 0.611 0.489-0.763 0.039 0.8436 1.057 0.610-1.830 VE-VCO2 slope 15.097 0.0001 1.097 1.047-1.149 0.087 0.7683 1.014 0.924-1.112 Peak HR 3.681 0.0550 0.970 0.940-1.001 0.125 0.7237 0.991 0.940-1.044 LVDd 24.743 <0.0001 1.129 1.076-1.184 1.405 0.2359 0.876 0.705-1.090 LVDs 29.859 <0.0001 1.115 1.072-1.159 6.035 0.0140 1.352 1.063-1.720 LVEF 19.937 <0.0001 0.908 0.870-0.947 2.216 0.1366 1.086 0.974-1.212
Cox proportional hazards analysis of cardiac events (secondary endpoint) in patients with SR Univariate Analysis Multivariate Analysis Variables χ2 p value HR 95% CI χ2 p value HR 95% CI Age 5.482 0.0192 1.025 1.004-1.046 3.040 0.0812 1.019 0.998-1.041 Gender 0.610 0.4350 1.246 0.718-2.162 3.813 0.0508 1.953 0.997-3.825 BMI 1.281 0.2577 0.962 0.899-1.029 2.973 0.0847 0.936 0.868-1.009 Peak VO2 33.922 <0.0001 0.878 0.840-0.917 10.419 0.0012 0.884 0.821-0.953 ΔVO2/ΔWR 26.983 <0.0001 0.789 0.722-0.863 1.859 0.1728 0.896 0.765-1.049 VE-VCO2 slope 16.175 <0.0001 1.046 1.023-1.068 0.329 0.5662 0.991 0.961-1.022 Peak HR 10.213 0.0014 0.985 0.975-0.994 0.506 0.4767 1.005 0.992-1.017 LVDd 17.273 <0.0001 1.050 1.026-1.074 0.896 0.3438 1.057 0.942-1.186 LVDs 20.839 <0.0001 1.041 1.023-1.060 0.029 0.8637 1.013 0.872-1.178 LVEF 16.701 <0.0001 0.975 0.963-0.987 0.259 0.6111 1.015 0.960-1.072
Cox proportional hazards analysis of cardiac deaths (primary endpoint) in patients with AF Univariate Analysis Multivariate Analysis Variables χ2 p value HR 95% CI χ2 p value HR 95% CI Age 0.001 0.9698 1.002 0.910-1.103 0.172 0.6781 1.049 0.838-1.312 Gender 0.824 0.3639 2.705 0.316-23.179 0.316 0.5740 2.748 0.081-93.225 BMI 0.531 0.4661 0.910 0.706-1.173 1.772 0.1832 1.709 0.776-3.761 Peak VO2 4.955 0.0260 0.757 0.593-0.967 0.486 0.4858 1.251 0.667-2.345 ΔVO2/ΔWR 4.946 0.0261 0.763 0.600-0.968 0.020 0.8874 0.937 0.378-2.320 VE-VCO2 slope 8.586 0.0034 1.090 1.029-1.154 3.907 0.0481 1.293 1.002-1.668 Peak HR 4.061 0.0439 0.970 0.942-0.999 3.304 0.0691 0.947 0.894-1.004 LVDd 0.651 0.4196 1.033 0.955-1.116 1.083 0.2980 0.461 0.107-1.984 LVDs 2.174 0.1403 1.044 0.986-1.106 1.086 0.2973 2.557 0.437-14.954 LVEF 4.180 0.0409 0.954 0.912-0.998 0.695 0.4045 1.261 0.731-2.175
Cox proportional hazards analysis of cardiac events (secondary endpoint) in patients with AF Univariate Analysis Multivariate Analysis Variables χ2 p value HR 95% CI χ2 p value HR 95% CI Age 2.978 0.0844 0.958 0.913-1.006 1.050 0.3056 0.969 0.913-1.029 Gender 0.032 0.8586 1.084 0.448-2.619 0.096 0.7569 1.212 0.359-4.093 BMI 3.008 0.0828 0.887 0.774-1.016 0.069 0.7931 0.975 0.807-1.178 Peak VO2 3.318 0.0685 0.921 0.843-1.006 0.384 0.5353 0.936 0.761-1.152 ΔVO2/ΔWR 2.201 0.1379 0.901 0.786-1.034 0.157 0.6915 1.067 0.775-1.469 VE-VCO2 slope 11.478 0.0007 1.049 1.021-1.079 4.501 0.0339 1.050 1.004-1.099 Peak HR 0.113 0.7369 0.998 0.987-1.009 0.624 0.4295 1.006 0.991-1.022 LVDd 7.362 0.0067 1.058 1.016-1.102 0.108 0.7425 0.915 0.539-1.554 LVDs 6.008 0.0142 1.044 1.009-1.081 0.402 0.5261 1.264 0.613-2.608 LVEF 3.089 0.0788 0.978 0.953-1.003 0.623 0.4301 1.113 0.853-1.451
Summary In patients with SR, peak VO2 and LVDs were found to be independent predictors for cardiac death and only peak VO2 was found to be an independent predictor for cardiac events from multivariate Cox proportional hazards analyses. In patients with AF, only VE-VCO2 slope was found to be an independent predictor for cardiac deaths and cardiac events.
Conclusion In patients with persistent atrial fibrillation, a strong predictor for future cardiac events is VE-VCO2 slope, while it is peak VO2 patients with sinus rhythm.