Association Between Chronic Obstructive Pulmonary Disease and All-Cause Mortality After Aortic Valve Replacement for Aortic Stenosis
2022; Elsevier BV; Volume: 190; Linguagem: Inglês
10.1016/j.amjcard.2022.11.007
ISSN1879-1913
AutoresRinchyenkhand Myagmardorj, Takeru Nabeta, Kensuke Hirasawa, Gurpreet K. Singh, Frank van der Kley, Arend de Weger, Nina Ajmone Marsan, Jeroen J. Bax, Victoria Delgado,
Tópico(s)Cardiac Imaging and Diagnostics
ResumoChronic obstructive pulmonary disease (COPD) and aortic stenosis (AS) are the most common diseases in which age plays a major role in the increase of their prevalence and when they co-exist, the outcomes prognosis worsens significantly. The aim of the present study was to evaluate the association between pulmonary functional parameters and all-cause mortality after aortic valve replacement (transcatheter or surgical). A total of 400 patients with severe AS and preoperative pulmonary functional test were retrospectively analyzed. Echocardiography and pulmonary functional parameters before aortic valve replacement were collected. COPD severity was defined according to criteria from the Society of Thoracic Surgeons. COPD was present in 128 patients (32%) with severe AS. Patients without COPD had smaller left ventricular (LV) mass and LV end-systolic volume and better LV function than the group with COPD. During a median follow-up of 32 months, 92 patients (23%) died. The survival rates were significantly lower in patients with moderate and severe COPD (log-rank p = 0.003). In the multivariable Cox regression analysis, any grade of COPD was associated with an approximately 2-fold increased risk of all-cause mortality (hazard ratio 1.933; 95% confidence interval 1.166 to 3.204; p = 0.011 for mild COPD and hazard ratio 2.028; 95% confidence interval 1.154 to 3.564; p = 0.014 for moderate or severe COPD). In addition to other clinical factors, any grade of COPD was associated with 2-fold increased risk of all-cause mortality. Chronic obstructive pulmonary disease (COPD) and aortic stenosis (AS) are the most common diseases in which age plays a major role in the increase of their prevalence and when they co-exist, the outcomes prognosis worsens significantly. The aim of the present study was to evaluate the association between pulmonary functional parameters and all-cause mortality after aortic valve replacement (transcatheter or surgical). A total of 400 patients with severe AS and preoperative pulmonary functional test were retrospectively analyzed. Echocardiography and pulmonary functional parameters before aortic valve replacement were collected. COPD severity was defined according to criteria from the Society of Thoracic Surgeons. COPD was present in 128 patients (32%) with severe AS. Patients without COPD had smaller left ventricular (LV) mass and LV end-systolic volume and better LV function than the group with COPD. During a median follow-up of 32 months, 92 patients (23%) died. The survival rates were significantly lower in patients with moderate and severe COPD (log-rank p = 0.003). In the multivariable Cox regression analysis, any grade of COPD was associated with an approximately 2-fold increased risk of all-cause mortality (hazard ratio 1.933; 95% confidence interval 1.166 to 3.204; p = 0.011 for mild COPD and hazard ratio 2.028; 95% confidence interval 1.154 to 3.564; p = 0.014 for moderate or severe COPD). In addition to other clinical factors, any grade of COPD was associated with 2-fold increased risk of all-cause mortality. Chronic obstructive pulmonary disease (COPD) is the most prevalent chronic pulmonary disease and is the third cause of death and years of life lost after ischemic heart disease and stroke.1World Health Organization. The top 10 causes of death. Available at:https://www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death/. Accessed on December 9, 2020.Google Scholar In addition, aortic stenosis (AS) is the most common valvular heart disease in the Western world.2Iung B Baron G Butchart EG Delahaye F Gohlke-Bärwolf C Levang OW Tornos P Vanoverschelde JL Vermeer F Boersma E Ravaud P Vahanian A A prospective survey of patients with valvular heart disease in Europe: the euro heart survey on valvular heart disease.Eur Heart J. 2003; 24: 1231-1243Crossref PubMed Scopus (2786) Google Scholar For both diseases (COPD and AS), age plays a major role in the increase of their prevalence and percentual change in mortality over the years. In severe AS, aortic valve replacement (AVR) is the only treatment that has demonstrated to improve survival.3Schwarz F Baumann P Manthey J Hoffmann M Schuler G Mehmel HC Schmitz W Kübler W The effect of aortic valve replacement on survival.Circulation. 1982; 66: 1105-1110Crossref PubMed Scopus (470) Google Scholar Yet, the presence of co-morbidities increases the operative risk and influences the outcomes negatively after AVR.4Nashef SA Roques F Sharples LD Nilsson J Smith C Goldstone AR Lockowandt U EuroSCORE II.Eur J Cardiothorac Surg. 2012; 41: 734-745Crossref PubMed Scopus (2032) Google Scholar The frequency of COPD among patients undergoing AVR due to severe AS ranges between 19% and 43%.5Mok M Nombela-Franco L Dumont E Urena M DeLarochellière R Doyle D Villeneuve J Côté M Ribeiro HB Allende R Laflamme J DeLarochellière H Laflamme L Amat-Santos I Pibarot P Maltais F Rodés-Cabau J Chronic obstructive pulmonary disease in patients undergoing transcatheter aortic valve implantation: insights on clinical outcomes, prognostic markers, and functional status changes.JACC Cardiovasc Interv. 2013; 6: 1072-1084Crossref PubMed Scopus (85) Google Scholar Notably, in a recent meta-analysis, COPD has been associated with an increased risk of all-cause mortality, with a hazard ratio of 1.34.6Liao YB He ZX Zhao ZG Wei X Zuo ZL Li YJ Xiong TY Xu YN Feng Y Chen M The relationship between chronic obstructive pulmonary disease and transcatheter aortic valve implantation–a systematic review and meta-analysis.Catheter Cardiovasc Interv. 2016; 87: 570-578Crossref PubMed Scopus (32) Google Scholar However, the definition of COPD varies across the studies and is not always based on the use of pulmonary function tests (PFTs). Accordingly, the aim of the present study was to evaluate the. association between pulmonary functional parameters and all-cause mortality after AVR in a large cohort of patients with severe AS. Patients with severe AS who underwent surgical or transcatheter AVR between January 2001 and July 2017 were screened retrospectively for the presence of documented COPD with functional lung test. Patients who received only medical therapy or aortic valve balloon dilatation or had incomplete pulmonary functional data were excluded (Figure 1). The decision of performing surgical or transcatheter AVR was based on the heart team's discussions.7Otto CM Kumbhani DJ Alexander KP Calhoon JH Desai MY Kaul S Lee JC Ruiz CE Vassileva CM. 2017 ACC Expert consensus decision pathway for transcatheter aortic valve replacement in the management of adults with aortic stenosis: a report of the American College of Cardiology task force on clinical expert consensus documents.J Am Coll Cardiol. 2017; 69 (Published correction appears in J Am Coll Cardiol 2017;69:1362): 1313-1346Crossref PubMed Scopus (377) Google Scholar,8Baumgartner H Falk V Bax JJ De Bonis M Hamm C Holm PJ Iung B Lancellotti P Lansac E Rodriguez Muñoz D Rosenhek R Sjögren J Tornos Mas P Vahanian A Walther T Wendler O Windecker S Zamorano JL ESC Scientific Document Group2017 ESC/EACTS Guidelines for the management of valvular heart disease.Eur Heart J. 2017; 38: 2739-2791Crossref PubMed Scopus (2) Google Scholar After AVR, patients were discharged from the hospital and followed up by the referring physician. From the electronic medical records of the Leiden University of Medical Center (EPD-vision and Hix, Leiden, The Netherlands), demographic and clinical data, including symptoms, co-morbidities, and medications, were collected. Furthermore, echocardiographic and PFTs were retrieved and analyzed. For the retrospective analysis of clinically collected data, the institutional review board approved the study and waived the need for patient written informed consent. PFTs (including plethysmography) were performed before AVR, according to the European Respiratory Society and American Thoracic Society recommendations.9Graham BL Brusasco V Burgos F Cooper BG Jensen R Kendrick A MacIntyre NR Thompson BR Wanger J Executive summary: 2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung.Eur Respir J. 2017; 49: 16e0016Crossref PubMed Scopus (95) Google Scholar Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), Tiffeneau index (ratio of FEV1/FVC), vital capacity (VC), peak expiratory flow, and inspiratory capacity were expressed as absolute values and percentage of a theoretical value calculated by the Global Lung Function 2012 equations.10Quanjer PH Stanojevic S Cole TJ Baur X Hall GL Culver BH Enright PL Hankinson JL Ip MS Zheng J Stocks J ERS Global Lung Function Initiative. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations.Eur Respir J. 2012; 40: 1324-1343Crossref PubMed Scopus (3730) Google Scholar Patients were divided according to the results of FEV1 and the categories defined in the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database: normal pulmonary function was defined by an FEV1 >75% of predicted, mild COPD if FEV1 was 60% to 75% of predicted, moderate COPD if FEV1 was 50% to 59% of predicted, and severe COPD when FEV1 <50% of predicted.11The Society of Thoracic Surgeons. STS Adult Cardiac Surgery Database Data Specifications, Version 2.81. Available at:https://www.sts.org/sites/default/files/documents/ACSD_DataSpecificationsV2_81.pdf. Accessed April 30, 2020.Google Scholar Patients underwent transthoracic echocardiography before AVR. Echocardiographic data were acquired with available ultrasound systems (Vivid-7, E9 and E95; GE Healthcare), triggered to electrocardiographic signal, and stored for subsequent offline analysis. The ultrasound systems were equipped with the MS5 and 4Vc-D 4-D matrix cardiac probes. The 2-dimensional, color, spectral continuous and pulsed-wave Doppler images were obtained from the parasternal, apical, and subcostal views. All images were digitally stored for offline analysis (EchoPAC version 203; GE-Vingmed, Horten, Norway). Left ventricular (LV) dimensions and function were assessed by measuring the end-diastolic diameter, end-systolic diameter, and interventricular septal thickness, as well as the posterior wall thickness on parasternal M-mode recordings, whereas the LV end-diastolic volume and end-systolic volume were measured from the apical 2- and 4-chamber views and the LV ejection fraction was derived using the biplane Simpson method. LV mass was calculated according to the Devereux formula and indexed for body surface area.12Lang RM Badano LP Mor-Avi V Afilalo J Armstrong A Ernande L Flachskampf FA Foster E Goldstein SA Kuznetsova T Lancellotti P Muraru D Picard MH Rietzschel ER Rudski L Spencer KT Tsang W Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.Eur Heart J Cardiovasc Imaging. 2015; 16 (Published correction appears in Eur Heart J Cardiovasc Imaging 2016;17:969): 233-270Crossref PubMed Scopus (4995) Google Scholar The peak jet velocity estimation was based on the continuous wave Doppler data from the apical 5- or 3-chamber views.13Baumgartner H Hung J Bermejo J Chambers JB Edvardsen T Goldstein S Lancellotti P LeFevre M Miller Jr, F Otto CM Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography.J Am Soc Echocardiogr. 2017; 30: 372-392Abstract Full Text Full Text PDF PubMed Scopus (643) Google Scholar The mean and peak transvalvular pressure gradients were calculated using the Bernoulli equation. The aortic valve area was calculated using the LV outflow tract diameter and velocity time integrals of the aortic valve and LV outflow tract.13Baumgartner H Hung J Bermejo J Chambers JB Edvardsen T Goldstein S Lancellotti P LeFevre M Miller Jr, F Otto CM Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography.J Am Soc Echocardiogr. 2017; 30: 372-392Abstract Full Text Full Text PDF PubMed Scopus (643) Google Scholar All other standard measurements were performed based on the recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging.12Lang RM Badano LP Mor-Avi V Afilalo J Armstrong A Ernande L Flachskampf FA Foster E Goldstein SA Kuznetsova T Lancellotti P Muraru D Picard MH Rietzschel ER Rudski L Spencer KT Tsang W Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.Eur Heart J Cardiovasc Imaging. 2015; 16 (Published correction appears in Eur Heart J Cardiovasc Imaging 2016;17:969): 233-270Crossref PubMed Scopus (4995) Google Scholar Patients were followed up for the occurrence of all-cause mortality after AVR. Survival data were completed for all patients and collected from the departmental cardiology information system, which is linked to municipal civil registries. Categorical variables are presented as numbers and percentages. Normally distributed continuous variables are expressed as mean with standard deviation, whereas non-normally distributed continuous variables are presented as median and interquartile range. The distribution of normality was verified using the Kolmogorov-Smirnov test and visual assessment of histograms. Continuous data were compared with 1-way analysis of variance for normally distributed variables and Kruskal-Wallis test was used for variables with non-normal distribution. For both continuous and categorical data, a Bonferroni post hoc analysis was added for 1-way ANOVA for comparison. Survival analysis was performed with the Kaplan-Meier curve method, taking the time of AVR as the onset of follow-up. Cumulative event-free rates were compared across groups with the log-rank test. To evaluate the association between COPD severity and all-cause mortality in patients treated with AVR, the univariable and multivariable Cox proportional hazards analysis was used. Clinically relevant variables were selected for univariable analysis, and statistically significant (p ≤0.05) variables were introduced as covariates in multivariable Cox proportional hazards models. A 2-sided p value <0.05 was considered statistically significant. Statistical analysis was performed using IBM SPSS version 25.0 (SPSS Inc., IBM Corp, Armonk, New York). Of 677 patients diagnosed with severe AS undergoing AVR, 400 patients (aged 78.0 years [71.0 to 84.0 ], 56.7% men) had documented preoperative PFT results. Demographic and clinical characteristics of the overall population, as well as the groups divided according to the STS definition of COPD severity are presented in Table 1. Mild, moderate, and severe COPD was present in 75 patients (19%), 31 patients (8%), and 22 patients (5%), respectively, whereas the remaining 68% had a normal PFT. Compared with patients without COPD, patients with moderate and severe COPD were more frequently male (56.7%) and more often received diuretics (53.3%) and statins (61.3%). In addition, New York Heart Association class III or IV heart failure symptoms were more frequent among patients with moderate and severe COPD than those without COPD.Table 1Patient characteristicsOverall (n = 400)STS classificationp Value*p values comparing among all 3 severity groups.None (n = 272)Mild COPD (n = 75)Moderate & severe COPD (n = 53)Age, years78.0(71.0-84.0)79.0(71.0-84.0)77.0(71.3-82.0)76.0(68.0-81.0)0.118Male, n (%)227 (57)138 (52)51 (64)38 (72)0.010Body mass index, kg/m225.8(23.8-28.7)26.0(24.0-29.1)26.0(23.6-28.6)24.6(23.2-27.8)0.114Beta-blocker, n (%)219 (55)153 (57)40 (50)26 (49)0.347ACEi/ARB, n (%)203 (51)136 (51)43 (54)24 (45)0.631Calcium antagonist, n (%)83 (21)55 (21)17 (21)11 (21)0.992Diuretics, n (%)213 (53)127 (48)49 (61)37 (70)0.003Aspirin, n (%)192 (48)135 (51)34 (43)23 (43)0.348OAC/NOAC, n (%)127 (32)77 (29)29 (36)21 (40)0.192Statin, n (%)245 (61)174 (65)40 (50)31 (59)0.046Hypertension, n (%)275 (69)185 (69)59 (74)31 (59)0.169Diabetes mellitus, n (%)104 (26)65 (24)21 (28)14 (26)0.467Hyperlipidemia, n (%)244 (61)172 (64)41 (51)31 (59)0.098CAD, n (%)205 (51)144 (54)37 (46)24 (45)0.314Previous MI, n (%)70 (18)50 (19)9 (11)11 (21)0.244Smoking history, n (%)148 (37)94 (35)29 (36)25 (47)0.256Active smoker, n (%)37 (9)19 (7)9 (11)9 (17)0.061Atrial fibrillation, n (%)119 (30)70 (26)30 (38)19 (36)0.089Stroke, n (%)25 (6)17 (6)7 (9)1 (2)0.277SAVR, n (%)127 (32)87 (33)24 (30)16 (30)0.827TAVR, n (%)273 (68)183 (67)53 (70)37 (70)NYHA class,%<0.0001I44 (11)39 (15)5 (6)0 (0.0)II155 (39)106 (40)27 (35)22 (42)III164 (42)106 (40)35 (45)23 (44)IV31 (8)13 (5)11 (14)7 (14)LogisticEuroSCORE,%10.4(6.4-16.3)10.2(6.4-15.9)10.9(6.7-19.0)10.5(6.5-19.6)0.667Concomitant CABG, n (%)51 (13)33 (12)10 (13)8 (15)0.860Creatinine, μmol/L88.0(74.0-111.0)87.0(73.0-107.0)93.5(77.0-121.5)91.0(77.0-118.0)0.156CABG = coronary artery bypass graft; CAD = coronary artery disease; EuroSCORE = the logistic European System for Cardiac Operative Risk Evaluation; MI = myocardial infarction; NYHA = New York Heart Association; SAVR=Surgical aortic valve replacement; STS = Society of Thoracic Surgeons.Values are presented as median (25th to 75th percentile) if not normally distributed. p values comparing among all 3 severity groups. Open table in a new tab CABG = coronary artery bypass graft; CAD = coronary artery disease; EuroSCORE = the logistic European System for Cardiac Operative Risk Evaluation; MI = myocardial infarction; NYHA = New York Heart Association; SAVR=Surgical aortic valve replacement; STS = Society of Thoracic Surgeons. Values are presented as median (25th to 75th percentile) if not normally distributed. In terms of echocardiographic characteristics, patients without COPD had smaller LV mass (117.1 vs 126.9 g/m2) and LV end-systolic volume (21.1 vs 24.1 ml/m2) and superior LV function (LVEF 58.0% vs 53.1%) than the group with mild COPD in Table 2. For the remaining echocardiographic variables, the groups of patients were comparable.Table 2Baseline echocardiographic characteristicsTotal (n = 400)STS classificationP ValueNone (n = 272)Mild COPD (n = 75)Moderate & Severe COPD (n = 53)LVEDD index, mm/m225.1(22.4-28.5)24.8(22.4-27.6)25.6(23.1-29.0)26.0(21.8-29.5)0.170LVESD index, mm/m217.6(14.4-21.2)17.3(14.0-20.5)18.6(14.5-23.8)18.6(15.1-22.9)0.114IVST, mm13.0(11.0-14.0)13.0(12.0-14.00)13.0(11.0-14.0)12.0(11.0-14.0)0.316LV mass index, g/m2119.1(100.9-142.2)117.1(97.8-137.5)126.9†p <0.05 vs none COPD group with Bonferroni post hoc analysis.(106.4-151.5)119.6(95.5-146.7)0.037*p values represent significant difference between COPD groups and are calculated by ANOVA (for normal distribution) and Kruskal-Wallis H (for non-normal distribution) test for continuous variables, and by chi-square test for categorical variables.LVEDV index, mL/m251.3(40.6-67.1)50.5(40.5-66.3)55.1(40.3-77.1)51.3(41.1-61.5)0.505LVESV index, mL/m222.3(15.2-38.4)21.1(14.7-32.9)24.1†p <0.05 vs none COPD group with Bonferroni post hoc analysis.(16.8-50.2)24.1(17.8-45.6)0.008*p values represent significant difference between COPD groups and are calculated by ANOVA (for normal distribution) and Kruskal-Wallis H (for non-normal distribution) test for continuous variables, and by chi-square test for categorical variables.LV stroke volume index, ml/m235.0(26.4-43.5)34.9(27.1-44.1)34.9(25.5-43.4)33.3(24.6-41.7)0.492LVEF, %57.0(43.0-64.0)58.0(46.0-65.0)53.1†p <0.05 vs none COPD group with Bonferroni post hoc analysis.(36.0-60.5)54.5 (39.7-61.8)0.005*p values represent significant difference between COPD groups and are calculated by ANOVA (for normal distribution) and Kruskal-Wallis H (for non-normal distribution) test for continuous variables, and by chi-square test for categorical variables.LAVI, ml/m238.9(27.1-52.2)38.4 (26.4-50.2)42.4 (32.1-58.2)38.2 (25.6-51.9)0.050AoV mean gradient, mmHg41.0(31.0-52.0)41.6(31.3-52.0)40.8(30.4-55.4)41.0(26.6-51.2)0.663AVA index, cm2/m20.4 ± 0.10.4 ± 0.10.4 ± 0.10.4 ± 0.10.951AoV = aortic valve; AVA = aortic valve area; IVST = intraventricular septal thickness; LAVI = left atrial volume index; LV = left ventricular; LVEDD = left ventricular end-diastolic dimension; LVEDV = left ventricular end-diastolic volume; LVEF = left ventricular ejection fraction; LVESD = left ventricular end-systolic dimension; LVESV = left ventricular end-systolic volume.Values are presented as mean ± SD with percentage (%) or median (25th to 75th percentile) if not normally distributed. p values represent significant difference between COPD groups and are calculated by ANOVA (for normal distribution) and Kruskal-Wallis H (for non-normal distribution) test for continuous variables, and by chi-square test for categorical variables.† p <0.05 vs none COPD group with Bonferroni post hoc analysis. Open table in a new tab AoV = aortic valve; AVA = aortic valve area; IVST = intraventricular septal thickness; LAVI = left atrial volume index; LV = left ventricular; LVEDD = left ventricular end-diastolic dimension; LVEDV = left ventricular end-diastolic volume; LVEF = left ventricular ejection fraction; LVESD = left ventricular end-systolic dimension; LVESV = left ventricular end-systolic volume. Values are presented as mean ± SD with percentage (%) or median (25th to 75th percentile) if not normally distributed. The results of the PFTs are presented in Table 3. The FVC, FEV1, Tiffeneau index, vital capacity, peak expiratory flow, and inspiratory capacity were the worst among patients with moderate and severe COPD (per definition) (p <0.0001).Table 3Pulmonary function testOverall (n = 400)STS classificationp ValueNone (n = 272)Mild COPD (n = 75)Moderate & Severe COPD (n = 53)FVC, % predicted93.3 ± 22.1102.8±17.977.0 ± 11.1†p <0.05 vs none COPD group with Bonferroni post hoc analysis.69.9 ± 19.4†p <0.05 vs none COPD group with Bonferroni post hoc analysis.‡p <0.05 vs mild COPD group with Bonferroni post hoc analysis.< 0.0001*p values represent significant difference between COPD groups and are calculated by Analysis of variance (ANOVA) (for normal distribution) and Kruskal-Wallis H (for non-normal distribution) test for continuous variables, and by chi-square test for categorical variables.FEV 1, % predicted87.4 ± 25.0100.6 ± 18.668.3 ± 4.7†p <0.05 vs none COPD group with Bonferroni post hoc analysis.49.3 ± 8.5†p <0.05 vs none COPD group with Bonferroni post hoc analysis.‡p <0.05 vs mild COPD group with Bonferroni post hoc analysis.< 0.0001*p values represent significant difference between COPD groups and are calculated by Analysis of variance (ANOVA) (for normal distribution) and Kruskal-Wallis H (for non-normal distribution) test for continuous variables, and by chi-square test for categorical variables.TiffeneauIndex (FEV1/FVC)73.7(67.2-79.8)76.4(71.4-81.4)69.0†p <0.05 vs none COPD group with Bonferroni post hoc analysis.(63.3-75.3)56.8†p <0.05 vs none COPD group with Bonferroni post hoc analysis.‡p <0.05 vs mild COPD group with Bonferroni post hoc analysis.(47.2-70.9)< 0.0001*p values represent significant difference between COPD groups and are calculated by Analysis of variance (ANOVA) (for normal distribution) and Kruskal-Wallis H (for non-normal distribution) test for continuous variables, and by chi-square test for categorical variables.VC, % predicted98.4 ± 45.8107.5 ± 51.479.0±13.8†p <0.05 vs none COPD group with Bonferroni post hoc analysis.80.5 ± 24.5†p <0.05 vs none COPD group with Bonferroni post hoc analysis.‡p <0.05 vs mild COPD group with Bonferroni post hoc analysis.< 0.0001*p values represent significant difference between COPD groups and are calculated by Analysis of variance (ANOVA) (for normal distribution) and Kruskal-Wallis H (for non-normal distribution) test for continuous variables, and by chi-square test for categorical variables.PEF, % predicted90.7 ± 42.8101.4 ± 45.874.6 ± 19.3†p <0.05 vs none COPD group with Bonferroni post hoc analysis.63.6 ± 12.6†p <0.05 vs none COPD group with Bonferroni post hoc analysis.‡p <0.05 vs mild COPD group with Bonferroni post hoc analysis.<0.0001*p values represent significant difference between COPD groups and are calculated by Analysis of variance (ANOVA) (for normal distribution) and Kruskal-Wallis H (for non-normal distribution) test for continuous variables, and by chi-square test for categorical variables.IC, % predicted96.6 ± 23.1103.3 ± 21.187.0 ± 14.8†p <0.05 vs none COPD group with Bonferroni post hoc analysis.78.6 ± 29.5†p <0.05 vs none COPD group with Bonferroni post hoc analysis.‡p <0.05 vs mild COPD group with Bonferroni post hoc analysis.<0.0001*p values represent significant difference between COPD groups and are calculated by Analysis of variance (ANOVA) (for normal distribution) and Kruskal-Wallis H (for non-normal distribution) test for continuous variables, and by chi-square test for categorical variables.FEV1 = Forced expiratory volume in 1 second; FVC = Forced vital capacity; IC = inspiratory capacity; PEF = peak expiratory flow; VC = vital capacity.Values are presented as mean ± SD with percentage (%) or median (25th to 75th percentile) if not normally distributed. p values represent significant difference between COPD groups and are calculated by Analysis of variance (ANOVA) (for normal distribution) and Kruskal-Wallis H (for non-normal distribution) test for continuous variables, and by chi-square test for categorical variables.† p <0.05 vs none COPD group with Bonferroni post hoc analysis.‡ p <0.05 vs mild COPD group with Bonferroni post hoc analysis. Open table in a new tab FEV1 = Forced expiratory volume in 1 second; FVC = Forced vital capacity; IC = inspiratory capacity; PEF = peak expiratory flow; VC = vital capacity. Values are presented as mean ± SD with percentage (%) or median (25th to 75th percentile) if not normally distributed. Over a median follow-up of 32 months (interquartile range 17 to 60 months), 92 patients (23%) died. The cumulative 1-, 2-, and 5-year survival rates for the overall population were 92%, 88%, and 81%, respectively. The survival rates were significantly lower in patients with moderate and severe COPD than patients without COPD (log-rank p = 0.004, Figure 2). There were significant differences in all-cause mortality between the no COPD group and mild COPD group (p = 0.007), as well as the no COPD group and moderate/severe COPD group (p = 0.008), respectively. The univariable and multivariable Cox regression analyses were constructed with variables known to be associated with outcomes in patients with COPD after AVR (Table 4). In univariable analysis, older age, higher body mass index, active smoking, diabetes mellitus, previous myocardial infarction, higher creatinine level, lower LV ejection fraction, and COPD were significantly associated with all-cause mortality. On multivariable Cox regression analysis, older age (hazard ratio [HR] 1.048; 95% confidence interval [CI] 1.022 to 1.075; p <0.0001), higher body mass index (HR 0.942; 95% CI 0.889 to 0.998; p = 0.041), active smoking (HR 2.115; 95% CI 1.198 to 3.732; p = 0.010), diabetes mellitus (HR 2.557; 95% CI 1.626 to 4.022; p <0.0001), creatinine level (HR 1.004; 95% CI 1.002 to 1.007), and COPD were independently associated with all-cause mortality. Remarkably, any grade of COPD was associated with approximately 2-fold increased risk of all-cause mortality (HR 1.933; 95% CI 1.166 to 3.204; p = 0.011 for mild COPD and HR 2.028; 95% CI 1.154 to 3.564; p = 0.014 for moderate and severe COPD, respectively).Table 4Associates of all-cause mortality after aortic valve replacementUnivariate analysisMultivariate Analysis*Univariate predictors with a p <0.05 were included in multivariate analysis.HR (95% Cl)p ValueHR (95% Cl)p ValueBaseline variablesAge (per 1 year increase)1.034 (1.011-1.058)0.0031.048 (1.022-1.075)< 0.0001Gender (yes/no)1.071 (0.704-1.630)0.748Body mass index, (per 1 kg/m2 increase)0.938 (0.888-0.990)0.0200.942 (0.889-0.998)0.041Beta-blocker (yes/no)0.903 (0.600-1.359)0.625Hypertension (yes/no)1.123 (0.713-1.769)0.617Smoking history (yes/no)1.237 (0.810-1.889)0.326Active smoker (yes/no)2.218 (1.293-3.803)0.0042.115 (1.198-3.732)0.010DM (yes/no)1.921 (1.257-2.937)0.0032.557 (1.626-4.022)< 0.0001Hyperlipidemia (yes/no)0.977 (0.646-1.478)0.912Previous MI (yes/no)1.912 (1.181-3.095)0.0081.593 (0.955-2.658)0.075CAD (yes/no)1.416 (0.937-2.141)0.099Atrial fibrillation (yes/no)1.318 (0.832-2.089)0.240Creatinine (per 1 μmol/L increase)1.002 (1.001-1.004)0.0111.004 (1.002-1.007)0.001LVEF (per 1% increase)0.977 (0.964-0.990)0.0000.979 (0.966-0.993)0.004COPD by STS definition0.0030.009None-ref-refMild COPD1.926 (1.188-3.121)0.0081.933 (1.166-3.204)0.011Moderate and severe COPD2.157 (1.256-3.706)0.0052.028 (1.154-3.564)0.014DM = diabetes mellitus; MI = myocardial infarction; CAD = coronary artery disease; LVEF = left ventricular ejection fraction; COPD = chronic obstructive pulmonary disease; STS = Society of Thoracic Surgeons; CI = confidence interval. Univariate predictors with a p <0.05 were included in multivariate analysis. Open table in a new tab DM = diabetes mellitus; MI = myocardial infarction; CAD = coronary artery disease; LVEF = left ventricular ejection fraction; COPD = chronic obstructive pulmonary disease; STS = Society of Thoracic Surgeons; CI = confidence interval. In this study, 1/3 of patients with severe AS undergoing AVR had COPD. COPD was independently associated with all-caus
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