Impact of bendopnea on postoperative outcomes in patients with severe aortic stenosis undergoing aortic valve replacement

Impact of bendopnea on postoperative outcomes in patients with severe aortic stenosis undergoing... Abstract OBJECTIVES Bendopnea is a recently described symptom of advanced heart failure. Its prevalence and prognostic utility in other cardiac conditions are unknown. METHODS We prospectively enrolled 108 consecutive patients (75 ± 3 years, 68% men) with severe symptomatic aortic stenosis referred for surgical aortic valve replacement (SAVR). Preoperatively, patients were tested for bendopnea, which was considered to be present when dyspnoea occurred within 30 s of bending forward. Univariable and stepwise multivariable analyses tested the association of bendopnea with preoperative echocardiographic parameters and postoperative clinical outcomes. RESULTS Bendopnea was present in 46 of 108 (42%) patients. The mean time of onset was 10.5 ± 3.4 s. Bendopnea was associated with higher estimated pulmonary artery systolic pressures [51 (11) mmHg vs 40 (11) mmHg), P < 0.0001], smaller aortic valve area [0.66 (0.16) cm2 vs 0.76 (0.13) cm2, P = 0.0006] and longer duration of mechanical ventilation (P = 0.002) and length of stay in the hospital (P = 0.007). Following SAVR, in-hospital mortality in those with bendopnea versus those without bendopnea was 13% vs 3% (P = 0.07). In multivariable analysis, bendopnea was associated with duration of mechanical ventilation (parameter estimate 2.4, P < 0.0001) and length of stay in the hospital (parameter estimate 10.2, P ≤ 0.0001). CONCLUSIONS Bendopnea was present in a sizeable minority of patients (42%) with severe aortic stenosis referred for SAVR. Bendopnea was associated with higher pulmonary artery systolic pressure and smaller aortic valve area preoperatively and with longer duration of mechanical ventilation and length of hospitalization postoperatively. These data suggest that bendopnea provides prognostic information in patients with severe aortic stenosis undergoing SAVR. Bendopnea , Physical examination , Aortic stenosis , Prognosis , Surgical aortic valve replacement INTRODUCTION Aortic stenosis (AS), the most common valvular heart disease in the elderly, is characterized by fixed aortic valve narrowing, left ventricular remodelling with hypertrophy and progressive diastolic dysfunction [1]. The cardinal manifestations of AS include dyspnoea on exertion, poor exercise tolerance, syncope, chest pain and development of heart failure. It has been well described that patients’ survival is limited once they become symptomatic [2–4], and the development of symptoms is an indication for aortic valve replacement (AVR) in patients with severe AS [5]. Recently, the symptom of bendopnea, or shortness of breath when bending forward such as when putting on shoes, has been described in patients with heart failure and was found to be associated with higher ventricular filling pressures, particularly in the setting of low cardiac index [6]. Bendopnea has also been shown to be associated with a higher VE/VCO2 on cardiopulmonary exercise testing, a validated marker of disease severity in patients with heart failure [7]. Furthermore, bendopnea was associated with an increased risk of adverse outcomes in ambulatory patients with heart failure [8] and with more advanced New York Heart Association (NYHA) class and higher mortality in patients admitted with decompensated heart failure [9]. Haemodynamic findings of severe AS can include elevated pulmonary capillary wedge pressure and potentially pulmonary hypertension and low cardiac output [10, 11]. Thus, it is possible that such patients may experience bendopnea. The frequency and prognostic value of bendopnea on patients with severe AS referred for surgical aortic valve replacement (SAVR) has not been previously reported. METHODS Study population This was a single site, prospective study examining the incidence and prognostic value of bendopnea in 128 consecutive patients with severe, symptomatic AS referred for SAVR in our institution between October 2015 and September 2016. Twenty patients were excluded from analysis for the following reasons: a severe restrictive or obstructive pulmonary process (n = 7), patients having an associated cardiac valve lesion more than moderate (n = 4), patients who were unable to bend forward for reasons not related to HF (n = 3) and patients who experienced headache (n = 5) or syncope (n = 1) during assessment of bendopnea. The data from the remaining 108 patients were included for analysis. Postoperative management in the intensive care unit largely follows a standardized approach. The research protocol was approved by the ethics committee of our institution (Hospital Universitario de Canarias). All patients gave written consent for inclusion. The presence of bendopnea was assessed as has been previously described [6, 8]. Between the 1st and 3rd days of admission, each patient was seated in a chair, asked to bend forward and touch their ankles and instructed to stop when they felt short of breath, palpitations, headache or general malaise. Usually, the bendopnea assessment was performed once on each patient [6], though in a minority of patients we performed it twice to confirm the results. Bendopnea was considered to be present only when dyspnoea occurred within 30 s of bending. Demographic and clinical data Demographic and clinical data were collected for all patients including age, gender, body mass index, cardiovascular risk factors, comorbidities, coronary artery disease (stenosis >70% on angiography), NYHA classification [12], clinician-estimated haemodynamic profiles (Profile A, patients with no evidence of congestion or hypoperfusion; Profile B, patients with evidence of congestion with adequate perfusion; Profile C, patients with evidence of congestion and hypoperfusion and Profile L, patients with evidence of hypoperfusion without congestion) [13], echocardiographic variables [left ventricular ejection fraction, estimated systolic pulmonary artery pressure, transaortic mean pressure gradient and aortic valve area (AVA)], laboratory values of creatinine and haemoglobin at the time of admission, medical therapy, EuroSCORE surgical mortality risk, length of stay (intensive care unit and cardiac surgical wards), duration of mechanical ventilation, in-hospital mortality and mortality within 30 days following surgery. Patients were contacted at 30 days following surgery to ascertain the vital status. Statistical analysis Continuous variables are presented as mean (standard deviation) or median (interquartile range) and categorical variables as count (percentage). The χ2 test or Fisher’s exact test [when the validity of the χ2 test was a concern due to low (<5) expected count of cells] was used to compare categorical variables, and the Kruskal–Wallis test was used to compare continuous variables. Stepwise multivariable linear or logistic regression models were performed to test the association of bendopnea, analysed as a categorical variable, with the outcomes of in-hospital mortality and 30-day postoperative mortality, duration of mechanical support and length of stay in the hospital. Enter and staying criteria were set at P ≤0.15. These models included the following variables: age, history of chronic obstructive pulmonary disease and all variables that were different between those with bendopnea and those without bendopnea including AVA, transaortic mean pressure gradient, pulmonary artery systolic pressure, history of permanent atrial fibrillation, NYHA classification and estimated haemodynamic profile. We entered the following as continuous variables in models: age, AVA, transaortic mean pressure gradient, pulmonary artery systolic pressure and cardiopulmonary bypass time; the remaining variables were treated as categorical variables. Statistical significance was set at 0.05, and all tests were 2-tailed. Statistical analysis was carried out using SPSS version 17.0 (Chicago, IL, USA) and SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). RESULTS Bendopnea was present in 46 of 108 (42%) subjects with mean time to onset of 11 ± 3 s. Eighty-eight patients had isolated SAVR, and 20 patients did undergo coronary artery bypass graft surgery and aortic valve replacement. The clinical characteristics of those with bendopnea and those without bendopnea are summarized in Table 1. Most patients were elderly men. There was no difference between those with bendopnea versus those without bendopnea with respect to age, gender, body mass index, presence of coronary artery disease, medical comorbidities and treatment, cardiopulmonary bypass time or surgical risk as assessed by the EuroSCORE. Table 1: Preoperative variables for those with bendopnea and without bendopnea Without bendopnea (n = 62) With bendopnea (n = 46) P-value Age (years) 75 (4) 74 (3) 0.23 Male 46 (74) 28 (61) 0.14 BMI (kg/m2) 26.40 (2.64) 26.15 (4.19) 0.29 Comorbidities  Hypertension 13 (21) 13 (28) 0.38  Diabetes mellitus 14 (22) 9 (19) 0.70  Smoking 14 (22) 8 (17) 0.50  Hyperlipidaemia 18 (29) 10 (21) 0.39  COPD 11 (17) 3 (6) 0.08  Previous CVD 2 (3) 2 (4) 1a  Previous PAD 5 (8) 3 (6) 1a  Previous MI 11 (17) 9 (19) 0.80  Permanent AF 16 (26) 5 (11) 0.05 CAD 1a  None 50 (81) 38 (83)  1-Vessel 8 (13) 6 (13)  2-Vessel 3 (5) 2 (4)  3-Vessel 1 (1) 0 (0) Echocardiographic variables  LVEF (%) 59 (9) 58 (7) 0.55  AVA (cm2) 0.76 (0.13) 0.66 (0.16) 0.0006  PASP (mmHg) 40 (11) 51 (11) <0.001  TMPG (mmHg) 48 (6) 53 (7) 0.00005 Medications  ACE inhibitor 45 (72) 39 (84%) 0.13  Angiotensin receptor blocker 17 (27) 7 (15%) 0.13  Aldosterone antagonist 39 (63) 25 (54) 0.37  Beta-blocker 50 (80) 37 (80) 0.97  Furosemide 62 (100) 46 (100) 1.0  Aspirin 24 (38) 23 (50) 0.24  HMG-CoA reductase inhibitors 57 (92) 42 (91) 1a NYHA classification <0.0001  Class I 0 (0) 0 (0)  Class II 35 (56) 4 (9)  Class III 23 (37) 26 (56)  Class IV 4 (7) 16 (35) Estimated haemodynamic profile 0.0004a  A 31 (50) 7 (15)  B 23 (37) 22 (48)  C 6 (10) 14 (30)  L 2 (3) 3 (7) EuroSCORE surgical mortality risk (%) 1.6 (1.2–1.9) 1.6 (1.3–2.3) 0.15 Cardiopulmonary bypass time (min) 52 (8) 51 (8) 0.5 Haemoglobin (g/dl) 14.20 (1.50) 14.44 (1.28) 0.64 Creatinine (mg/dl) 0.84 (0.18) 0.82 (0.20) 0.60 Without bendopnea (n = 62) With bendopnea (n = 46) P-value Age (years) 75 (4) 74 (3) 0.23 Male 46 (74) 28 (61) 0.14 BMI (kg/m2) 26.40 (2.64) 26.15 (4.19) 0.29 Comorbidities  Hypertension 13 (21) 13 (28) 0.38  Diabetes mellitus 14 (22) 9 (19) 0.70  Smoking 14 (22) 8 (17) 0.50  Hyperlipidaemia 18 (29) 10 (21) 0.39  COPD 11 (17) 3 (6) 0.08  Previous CVD 2 (3) 2 (4) 1a  Previous PAD 5 (8) 3 (6) 1a  Previous MI 11 (17) 9 (19) 0.80  Permanent AF 16 (26) 5 (11) 0.05 CAD 1a  None 50 (81) 38 (83)  1-Vessel 8 (13) 6 (13)  2-Vessel 3 (5) 2 (4)  3-Vessel 1 (1) 0 (0) Echocardiographic variables  LVEF (%) 59 (9) 58 (7) 0.55  AVA (cm2) 0.76 (0.13) 0.66 (0.16) 0.0006  PASP (mmHg) 40 (11) 51 (11) <0.001  TMPG (mmHg) 48 (6) 53 (7) 0.00005 Medications  ACE inhibitor 45 (72) 39 (84%) 0.13  Angiotensin receptor blocker 17 (27) 7 (15%) 0.13  Aldosterone antagonist 39 (63) 25 (54) 0.37  Beta-blocker 50 (80) 37 (80) 0.97  Furosemide 62 (100) 46 (100) 1.0  Aspirin 24 (38) 23 (50) 0.24  HMG-CoA reductase inhibitors 57 (92) 42 (91) 1a NYHA classification <0.0001  Class I 0 (0) 0 (0)  Class II 35 (56) 4 (9)  Class III 23 (37) 26 (56)  Class IV 4 (7) 16 (35) Estimated haemodynamic profile 0.0004a  A 31 (50) 7 (15)  B 23 (37) 22 (48)  C 6 (10) 14 (30)  L 2 (3) 3 (7) EuroSCORE surgical mortality risk (%) 1.6 (1.2–1.9) 1.6 (1.3–2.3) 0.15 Cardiopulmonary bypass time (min) 52 (8) 51 (8) 0.5 Haemoglobin (g/dl) 14.20 (1.50) 14.44 (1.28) 0.64 Creatinine (mg/dl) 0.84 (0.18) 0.82 (0.20) 0.60 Data are presented as mean (SD), median (interquartile change) or n (%). a The Fisher’s exact test. Other categorical P-values are from the χ2 test. ACEI: angiotensin-converting enzyme inhibitor; AF: atrial fibrillation; AVA: aortic valve area; BMI: body mass index; CAD: coronary artery disease; CVD: cerebrovascular disease; COPD: chronic obstructive pulmonary disease; LVEF: left ventricular ejection fraction; MI: myocardial infarction; NYHA: New York Heart Association; PAD: peripheral artery disease; PASP: pulmonary artery systolic pressure; SD: standard deviation; TMPG: transaortic mean pressure gradient. Table 1: Preoperative variables for those with bendopnea and without bendopnea Without bendopnea (n = 62) With bendopnea (n = 46) P-value Age (years) 75 (4) 74 (3) 0.23 Male 46 (74) 28 (61) 0.14 BMI (kg/m2) 26.40 (2.64) 26.15 (4.19) 0.29 Comorbidities  Hypertension 13 (21) 13 (28) 0.38  Diabetes mellitus 14 (22) 9 (19) 0.70  Smoking 14 (22) 8 (17) 0.50  Hyperlipidaemia 18 (29) 10 (21) 0.39  COPD 11 (17) 3 (6) 0.08  Previous CVD 2 (3) 2 (4) 1a  Previous PAD 5 (8) 3 (6) 1a  Previous MI 11 (17) 9 (19) 0.80  Permanent AF 16 (26) 5 (11) 0.05 CAD 1a  None 50 (81) 38 (83)  1-Vessel 8 (13) 6 (13)  2-Vessel 3 (5) 2 (4)  3-Vessel 1 (1) 0 (0) Echocardiographic variables  LVEF (%) 59 (9) 58 (7) 0.55  AVA (cm2) 0.76 (0.13) 0.66 (0.16) 0.0006  PASP (mmHg) 40 (11) 51 (11) <0.001  TMPG (mmHg) 48 (6) 53 (7) 0.00005 Medications  ACE inhibitor 45 (72) 39 (84%) 0.13  Angiotensin receptor blocker 17 (27) 7 (15%) 0.13  Aldosterone antagonist 39 (63) 25 (54) 0.37  Beta-blocker 50 (80) 37 (80) 0.97  Furosemide 62 (100) 46 (100) 1.0  Aspirin 24 (38) 23 (50) 0.24  HMG-CoA reductase inhibitors 57 (92) 42 (91) 1a NYHA classification <0.0001  Class I 0 (0) 0 (0)  Class II 35 (56) 4 (9)  Class III 23 (37) 26 (56)  Class IV 4 (7) 16 (35) Estimated haemodynamic profile 0.0004a  A 31 (50) 7 (15)  B 23 (37) 22 (48)  C 6 (10) 14 (30)  L 2 (3) 3 (7) EuroSCORE surgical mortality risk (%) 1.6 (1.2–1.9) 1.6 (1.3–2.3) 0.15 Cardiopulmonary bypass time (min) 52 (8) 51 (8) 0.5 Haemoglobin (g/dl) 14.20 (1.50) 14.44 (1.28) 0.64 Creatinine (mg/dl) 0.84 (0.18) 0.82 (0.20) 0.60 Without bendopnea (n = 62) With bendopnea (n = 46) P-value Age (years) 75 (4) 74 (3) 0.23 Male 46 (74) 28 (61) 0.14 BMI (kg/m2) 26.40 (2.64) 26.15 (4.19) 0.29 Comorbidities  Hypertension 13 (21) 13 (28) 0.38  Diabetes mellitus 14 (22) 9 (19) 0.70  Smoking 14 (22) 8 (17) 0.50  Hyperlipidaemia 18 (29) 10 (21) 0.39  COPD 11 (17) 3 (6) 0.08  Previous CVD 2 (3) 2 (4) 1a  Previous PAD 5 (8) 3 (6) 1a  Previous MI 11 (17) 9 (19) 0.80  Permanent AF 16 (26) 5 (11) 0.05 CAD 1a  None 50 (81) 38 (83)  1-Vessel 8 (13) 6 (13)  2-Vessel 3 (5) 2 (4)  3-Vessel 1 (1) 0 (0) Echocardiographic variables  LVEF (%) 59 (9) 58 (7) 0.55  AVA (cm2) 0.76 (0.13) 0.66 (0.16) 0.0006  PASP (mmHg) 40 (11) 51 (11) <0.001  TMPG (mmHg) 48 (6) 53 (7) 0.00005 Medications  ACE inhibitor 45 (72) 39 (84%) 0.13  Angiotensin receptor blocker 17 (27) 7 (15%) 0.13  Aldosterone antagonist 39 (63) 25 (54) 0.37  Beta-blocker 50 (80) 37 (80) 0.97  Furosemide 62 (100) 46 (100) 1.0  Aspirin 24 (38) 23 (50) 0.24  HMG-CoA reductase inhibitors 57 (92) 42 (91) 1a NYHA classification <0.0001  Class I 0 (0) 0 (0)  Class II 35 (56) 4 (9)  Class III 23 (37) 26 (56)  Class IV 4 (7) 16 (35) Estimated haemodynamic profile 0.0004a  A 31 (50) 7 (15)  B 23 (37) 22 (48)  C 6 (10) 14 (30)  L 2 (3) 3 (7) EuroSCORE surgical mortality risk (%) 1.6 (1.2–1.9) 1.6 (1.3–2.3) 0.15 Cardiopulmonary bypass time (min) 52 (8) 51 (8) 0.5 Haemoglobin (g/dl) 14.20 (1.50) 14.44 (1.28) 0.64 Creatinine (mg/dl) 0.84 (0.18) 0.82 (0.20) 0.60 Data are presented as mean (SD), median (interquartile change) or n (%). a The Fisher’s exact test. Other categorical P-values are from the χ2 test. ACEI: angiotensin-converting enzyme inhibitor; AF: atrial fibrillation; AVA: aortic valve area; BMI: body mass index; CAD: coronary artery disease; CVD: cerebrovascular disease; COPD: chronic obstructive pulmonary disease; LVEF: left ventricular ejection fraction; MI: myocardial infarction; NYHA: New York Heart Association; PAD: peripheral artery disease; PASP: pulmonary artery systolic pressure; SD: standard deviation; TMPG: transaortic mean pressure gradient. Patients with bendopnea versus patients without bendopnea were more impaired as assessed by NYHA functional class. There was also a difference in estimated haemodynamic profiles between those with bendopnea and those without bendopnea. Specifically, the vast majority of those without bendopnea were classified in haemodynamic Profiles A (50%) or B (37%), whereas the vast majority of those with bendopnea were classified as haemodynamic Profiles B (48%) and C (30%). As assessed by echocardiography, patients with bendopnea had higher pulmonary artery systolic pressures (P < 0.0001), smaller AVAs (P = 0.0006) and higher transaortic mean pressure gradient (P < 0.001), but there was no difference in left ventricular ejection fraction between the two groups whether or not left ventricular ejection fraction was analysed as a continuous (P = 0.55) or categorical (P = 0.4) variable. The postoperative characteristics of subjects with bendopnea and without bendopnea are summarized in Table 2. There was a numerically higher rate of in-hospital mortality in those with bendopnea compared to those without bendopnea, although this difference did not reach statistical significance. In-hospital mortality was due to organ failure and cardiopulmonary bypass-related systemic inflammatory response syndrome. There was also a trend towards higher rate of 30-day postoperative mortality in those with bendopnea. Patients with bendopnea had longer duration of mechanical ventilation and length of stay in the hospital. Table 2: Postoperative variables for patients with bendopnea and patients without bendopnea Without bendopnea (n = 62) With bendopnea (n = 46) P-value In-hospital mortality 2 (3) 6 (13) 0.07a 30-Day postoperative mortality 3 (5) 8 (17) 0.05a Duration of mechanical ventilation (h) 13.5 (10–16) 18 (12–23) 0.004 Length of stay in the hospital (days) 9 (8–10) 11 (8–12) 0.009 Without bendopnea (n = 62) With bendopnea (n = 46) P-value In-hospital mortality 2 (3) 6 (13) 0.07a 30-Day postoperative mortality 3 (5) 8 (17) 0.05a Duration of mechanical ventilation (h) 13.5 (10–16) 18 (12–23) 0.004 Length of stay in the hospital (days) 9 (8–10) 11 (8–12) 0.009 Data are presented as mean (SD), n (%) or median (25th–75th percentile). a The Fisher’s exact test. Table 2: Postoperative variables for patients with bendopnea and patients without bendopnea Without bendopnea (n = 62) With bendopnea (n = 46) P-value In-hospital mortality 2 (3) 6 (13) 0.07a 30-Day postoperative mortality 3 (5) 8 (17) 0.05a Duration of mechanical ventilation (h) 13.5 (10–16) 18 (12–23) 0.004 Length of stay in the hospital (days) 9 (8–10) 11 (8–12) 0.009 Without bendopnea (n = 62) With bendopnea (n = 46) P-value In-hospital mortality 2 (3) 6 (13) 0.07a 30-Day postoperative mortality 3 (5) 8 (17) 0.05a Duration of mechanical ventilation (h) 13.5 (10–16) 18 (12–23) 0.004 Length of stay in the hospital (days) 9 (8–10) 11 (8–12) 0.009 Data are presented as mean (SD), n (%) or median (25th–75th percentile). a The Fisher’s exact test. In univariable analysis, the association of bendopnea with in-hospital mortality did not reach statistical significance [odds ratio (OR) 4.5, 95% confidence interval (CI) 0.88–23.42; P = 0.07], but the association with 30-day postoperative mortality was significant (OR 4.2, 95% CI 1.05–16.9; P = 0.04). Bendopnea was associated with duration of mechanical support (regression coefficient 4.0, t = 3.2, P = 0.002) and length of stay in the hospital (regression coefficient 1.5, t = 2.7, P = 0.007). In multivariable analysis, only bendopnea (OR 10.1, 95% CI 1.6–64.6; P = 0.02) and age (OR 1.4, 95% CI 1.007–1.833; P = 0.05) were associated with an increased risk of in-hospital mortality, but no variables were associated with 30-day postoperative mortality. Bendopnea was also associated with duration of mechanical ventilation (parameter estimate 4.5, P = 0.0009) and length of stay in the hospital (parameter estimate 2.4, P < 0.0001). There were no other variables that were significant for duration of mechanical ventilation. The only other variables associated with length of stay in the hospital were estimated haemodynamic Profile L (parameter estimate −3.7, P = 0.003) and echocardiographic transaortic mean pressure gradient (parameter estimate −0.11, P = 0.01). DISCUSSION To our knowledge, this is the first study demonstrating that bendopnea was common and associated with adverse outcomes following SAVR in patients with severe AS. Specifically, we found that 42% of subjects with severe AS had bendopnea and that this symptom was associated with higher pulmonary artery pressures and a smaller AVA and was associated with increased risk of adverse outcomes following SAVR including a longer duration of mechanical ventilation and length of stay in the hospital. These data suggest that bendopnea provides prognostic information in the patients with severe symptomatic AS referred for AVR. Degenerative AS could be viewed as a disease with a silent phase of sclerosis and calcification of the valve, followed by progression of AS severity with different grades of left ventricular involvement. Once the AS is classified as severe, patients develop symptoms at different stages of the disease process [14]. The physical examination is essential in the diagnosis and management of patients with AS. Increased ventricular filling pressures in these patients lead to congestive symptoms that cause decompensated HF and hospital admissions [14]. We found that bendopnea was present in a sizeable minority (42%) of patients with severe symptomatic AS admitted in our centre. Previous studies have demonstrated a prevalence between 18% and 48% in populations of HF [6–9]. There are several novel aspects of our study. This is the first study that assessed the prevalence and prognostic value of bendopnea in patients with valvular heart disease (specifically AS). Second, the association of bendopnea with subsequent risk of adverse outcome following cardiac surgery (length of stay in the hospital, longer mechanical ventilation and possibly mortality) has not been demonstrated previously. The duration of mechanical ventilation is one of the most important clinical factors which predict outcomes in cardiac surgery [15]. The duration of mechanical ventilation is also associated with pulmonary venous hypertension [16]. In our study, patients with bendopnea had a longer duration of the mechanical ventilation. Given that bendopnea was associated with an elevated pulmonary capillary wedge pressure [6], an important contributor to secondary pulmonary hypertension [17], it may not be surprising that bendopnea is associated with an increased duration of mechanical ventilation. Clinicians often need to identify patients who are likely to require a longer period of high dependency care after cardiac surgery to allow for appropriate preoperative planning [18], especially because prolonged intensive care unit and ward stay in patients undergoing cardiac surgery increases overall hospital costs [19, 20]. Our data suggest that an assessment for bendopnea, an easily performed and inexpensive test, might assist in this manner. Previously, NYHA functional class was found to be an independent predictor of length of stay in the hospital [21]. Such data are supportive of the plausibility of an association of bendopnea with length of stay in the hospital, given that bendopnea itself has been shown to be associated with advanced NYHA functional class [9]. Limitations Our study has limitations. This was a single-centre study; thus, the results may not be generalizable. As described, 20 subjects were excluded from analysis, and this too may impact generalizability. Also, we did not systematically evaluate the factors which led physicians to retain a patient longer in the hospital. It is known that length of stay in the hospital may be influenced by non-medical determinants [22]. For example, we did not collect potential social reasons for delay in hospital discharge, although that would not expect to be associated with bendopnea status. Our sample size was small as was our event rates of in-hospital mortality and 30-day postoperative mortality, which may have impacted the robustness of the associations with clinical postoperative variables. Nevertheless, these data suggest that bendopnea was a prognostic marker in the patients with severe symptomatic AS referred for AVR, though we recognize further validation studies are needed. Finally, we also tested a number of outcomes, thus increasing the chance of false associations. CONCLUSION Bendopnea was present in a sizeable minority of patients with severe symptomatic AS referred for SAVR. 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Impact of bendopnea on postoperative outcomes in patients with severe aortic stenosis undergoing aortic valve replacement

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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1569-9293
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10.1093/icvts/ivy174
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Abstract

Abstract OBJECTIVES Bendopnea is a recently described symptom of advanced heart failure. Its prevalence and prognostic utility in other cardiac conditions are unknown. METHODS We prospectively enrolled 108 consecutive patients (75 ± 3 years, 68% men) with severe symptomatic aortic stenosis referred for surgical aortic valve replacement (SAVR). Preoperatively, patients were tested for bendopnea, which was considered to be present when dyspnoea occurred within 30 s of bending forward. Univariable and stepwise multivariable analyses tested the association of bendopnea with preoperative echocardiographic parameters and postoperative clinical outcomes. RESULTS Bendopnea was present in 46 of 108 (42%) patients. The mean time of onset was 10.5 ± 3.4 s. Bendopnea was associated with higher estimated pulmonary artery systolic pressures [51 (11) mmHg vs 40 (11) mmHg), P < 0.0001], smaller aortic valve area [0.66 (0.16) cm2 vs 0.76 (0.13) cm2, P = 0.0006] and longer duration of mechanical ventilation (P = 0.002) and length of stay in the hospital (P = 0.007). Following SAVR, in-hospital mortality in those with bendopnea versus those without bendopnea was 13% vs 3% (P = 0.07). In multivariable analysis, bendopnea was associated with duration of mechanical ventilation (parameter estimate 2.4, P < 0.0001) and length of stay in the hospital (parameter estimate 10.2, P ≤ 0.0001). CONCLUSIONS Bendopnea was present in a sizeable minority of patients (42%) with severe aortic stenosis referred for SAVR. Bendopnea was associated with higher pulmonary artery systolic pressure and smaller aortic valve area preoperatively and with longer duration of mechanical ventilation and length of hospitalization postoperatively. These data suggest that bendopnea provides prognostic information in patients with severe aortic stenosis undergoing SAVR. Bendopnea , Physical examination , Aortic stenosis , Prognosis , Surgical aortic valve replacement INTRODUCTION Aortic stenosis (AS), the most common valvular heart disease in the elderly, is characterized by fixed aortic valve narrowing, left ventricular remodelling with hypertrophy and progressive diastolic dysfunction [1]. The cardinal manifestations of AS include dyspnoea on exertion, poor exercise tolerance, syncope, chest pain and development of heart failure. It has been well described that patients’ survival is limited once they become symptomatic [2–4], and the development of symptoms is an indication for aortic valve replacement (AVR) in patients with severe AS [5]. Recently, the symptom of bendopnea, or shortness of breath when bending forward such as when putting on shoes, has been described in patients with heart failure and was found to be associated with higher ventricular filling pressures, particularly in the setting of low cardiac index [6]. Bendopnea has also been shown to be associated with a higher VE/VCO2 on cardiopulmonary exercise testing, a validated marker of disease severity in patients with heart failure [7]. Furthermore, bendopnea was associated with an increased risk of adverse outcomes in ambulatory patients with heart failure [8] and with more advanced New York Heart Association (NYHA) class and higher mortality in patients admitted with decompensated heart failure [9]. Haemodynamic findings of severe AS can include elevated pulmonary capillary wedge pressure and potentially pulmonary hypertension and low cardiac output [10, 11]. Thus, it is possible that such patients may experience bendopnea. The frequency and prognostic value of bendopnea on patients with severe AS referred for surgical aortic valve replacement (SAVR) has not been previously reported. METHODS Study population This was a single site, prospective study examining the incidence and prognostic value of bendopnea in 128 consecutive patients with severe, symptomatic AS referred for SAVR in our institution between October 2015 and September 2016. Twenty patients were excluded from analysis for the following reasons: a severe restrictive or obstructive pulmonary process (n = 7), patients having an associated cardiac valve lesion more than moderate (n = 4), patients who were unable to bend forward for reasons not related to HF (n = 3) and patients who experienced headache (n = 5) or syncope (n = 1) during assessment of bendopnea. The data from the remaining 108 patients were included for analysis. Postoperative management in the intensive care unit largely follows a standardized approach. The research protocol was approved by the ethics committee of our institution (Hospital Universitario de Canarias). All patients gave written consent for inclusion. The presence of bendopnea was assessed as has been previously described [6, 8]. Between the 1st and 3rd days of admission, each patient was seated in a chair, asked to bend forward and touch their ankles and instructed to stop when they felt short of breath, palpitations, headache or general malaise. Usually, the bendopnea assessment was performed once on each patient [6], though in a minority of patients we performed it twice to confirm the results. Bendopnea was considered to be present only when dyspnoea occurred within 30 s of bending. Demographic and clinical data Demographic and clinical data were collected for all patients including age, gender, body mass index, cardiovascular risk factors, comorbidities, coronary artery disease (stenosis >70% on angiography), NYHA classification [12], clinician-estimated haemodynamic profiles (Profile A, patients with no evidence of congestion or hypoperfusion; Profile B, patients with evidence of congestion with adequate perfusion; Profile C, patients with evidence of congestion and hypoperfusion and Profile L, patients with evidence of hypoperfusion without congestion) [13], echocardiographic variables [left ventricular ejection fraction, estimated systolic pulmonary artery pressure, transaortic mean pressure gradient and aortic valve area (AVA)], laboratory values of creatinine and haemoglobin at the time of admission, medical therapy, EuroSCORE surgical mortality risk, length of stay (intensive care unit and cardiac surgical wards), duration of mechanical ventilation, in-hospital mortality and mortality within 30 days following surgery. Patients were contacted at 30 days following surgery to ascertain the vital status. Statistical analysis Continuous variables are presented as mean (standard deviation) or median (interquartile range) and categorical variables as count (percentage). The χ2 test or Fisher’s exact test [when the validity of the χ2 test was a concern due to low (<5) expected count of cells] was used to compare categorical variables, and the Kruskal–Wallis test was used to compare continuous variables. Stepwise multivariable linear or logistic regression models were performed to test the association of bendopnea, analysed as a categorical variable, with the outcomes of in-hospital mortality and 30-day postoperative mortality, duration of mechanical support and length of stay in the hospital. Enter and staying criteria were set at P ≤0.15. These models included the following variables: age, history of chronic obstructive pulmonary disease and all variables that were different between those with bendopnea and those without bendopnea including AVA, transaortic mean pressure gradient, pulmonary artery systolic pressure, history of permanent atrial fibrillation, NYHA classification and estimated haemodynamic profile. We entered the following as continuous variables in models: age, AVA, transaortic mean pressure gradient, pulmonary artery systolic pressure and cardiopulmonary bypass time; the remaining variables were treated as categorical variables. Statistical significance was set at 0.05, and all tests were 2-tailed. Statistical analysis was carried out using SPSS version 17.0 (Chicago, IL, USA) and SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). RESULTS Bendopnea was present in 46 of 108 (42%) subjects with mean time to onset of 11 ± 3 s. Eighty-eight patients had isolated SAVR, and 20 patients did undergo coronary artery bypass graft surgery and aortic valve replacement. The clinical characteristics of those with bendopnea and those without bendopnea are summarized in Table 1. Most patients were elderly men. There was no difference between those with bendopnea versus those without bendopnea with respect to age, gender, body mass index, presence of coronary artery disease, medical comorbidities and treatment, cardiopulmonary bypass time or surgical risk as assessed by the EuroSCORE. Table 1: Preoperative variables for those with bendopnea and without bendopnea Without bendopnea (n = 62) With bendopnea (n = 46) P-value Age (years) 75 (4) 74 (3) 0.23 Male 46 (74) 28 (61) 0.14 BMI (kg/m2) 26.40 (2.64) 26.15 (4.19) 0.29 Comorbidities  Hypertension 13 (21) 13 (28) 0.38  Diabetes mellitus 14 (22) 9 (19) 0.70  Smoking 14 (22) 8 (17) 0.50  Hyperlipidaemia 18 (29) 10 (21) 0.39  COPD 11 (17) 3 (6) 0.08  Previous CVD 2 (3) 2 (4) 1a  Previous PAD 5 (8) 3 (6) 1a  Previous MI 11 (17) 9 (19) 0.80  Permanent AF 16 (26) 5 (11) 0.05 CAD 1a  None 50 (81) 38 (83)  1-Vessel 8 (13) 6 (13)  2-Vessel 3 (5) 2 (4)  3-Vessel 1 (1) 0 (0) Echocardiographic variables  LVEF (%) 59 (9) 58 (7) 0.55  AVA (cm2) 0.76 (0.13) 0.66 (0.16) 0.0006  PASP (mmHg) 40 (11) 51 (11) <0.001  TMPG (mmHg) 48 (6) 53 (7) 0.00005 Medications  ACE inhibitor 45 (72) 39 (84%) 0.13  Angiotensin receptor blocker 17 (27) 7 (15%) 0.13  Aldosterone antagonist 39 (63) 25 (54) 0.37  Beta-blocker 50 (80) 37 (80) 0.97  Furosemide 62 (100) 46 (100) 1.0  Aspirin 24 (38) 23 (50) 0.24  HMG-CoA reductase inhibitors 57 (92) 42 (91) 1a NYHA classification <0.0001  Class I 0 (0) 0 (0)  Class II 35 (56) 4 (9)  Class III 23 (37) 26 (56)  Class IV 4 (7) 16 (35) Estimated haemodynamic profile 0.0004a  A 31 (50) 7 (15)  B 23 (37) 22 (48)  C 6 (10) 14 (30)  L 2 (3) 3 (7) EuroSCORE surgical mortality risk (%) 1.6 (1.2–1.9) 1.6 (1.3–2.3) 0.15 Cardiopulmonary bypass time (min) 52 (8) 51 (8) 0.5 Haemoglobin (g/dl) 14.20 (1.50) 14.44 (1.28) 0.64 Creatinine (mg/dl) 0.84 (0.18) 0.82 (0.20) 0.60 Without bendopnea (n = 62) With bendopnea (n = 46) P-value Age (years) 75 (4) 74 (3) 0.23 Male 46 (74) 28 (61) 0.14 BMI (kg/m2) 26.40 (2.64) 26.15 (4.19) 0.29 Comorbidities  Hypertension 13 (21) 13 (28) 0.38  Diabetes mellitus 14 (22) 9 (19) 0.70  Smoking 14 (22) 8 (17) 0.50  Hyperlipidaemia 18 (29) 10 (21) 0.39  COPD 11 (17) 3 (6) 0.08  Previous CVD 2 (3) 2 (4) 1a  Previous PAD 5 (8) 3 (6) 1a  Previous MI 11 (17) 9 (19) 0.80  Permanent AF 16 (26) 5 (11) 0.05 CAD 1a  None 50 (81) 38 (83)  1-Vessel 8 (13) 6 (13)  2-Vessel 3 (5) 2 (4)  3-Vessel 1 (1) 0 (0) Echocardiographic variables  LVEF (%) 59 (9) 58 (7) 0.55  AVA (cm2) 0.76 (0.13) 0.66 (0.16) 0.0006  PASP (mmHg) 40 (11) 51 (11) <0.001  TMPG (mmHg) 48 (6) 53 (7) 0.00005 Medications  ACE inhibitor 45 (72) 39 (84%) 0.13  Angiotensin receptor blocker 17 (27) 7 (15%) 0.13  Aldosterone antagonist 39 (63) 25 (54) 0.37  Beta-blocker 50 (80) 37 (80) 0.97  Furosemide 62 (100) 46 (100) 1.0  Aspirin 24 (38) 23 (50) 0.24  HMG-CoA reductase inhibitors 57 (92) 42 (91) 1a NYHA classification <0.0001  Class I 0 (0) 0 (0)  Class II 35 (56) 4 (9)  Class III 23 (37) 26 (56)  Class IV 4 (7) 16 (35) Estimated haemodynamic profile 0.0004a  A 31 (50) 7 (15)  B 23 (37) 22 (48)  C 6 (10) 14 (30)  L 2 (3) 3 (7) EuroSCORE surgical mortality risk (%) 1.6 (1.2–1.9) 1.6 (1.3–2.3) 0.15 Cardiopulmonary bypass time (min) 52 (8) 51 (8) 0.5 Haemoglobin (g/dl) 14.20 (1.50) 14.44 (1.28) 0.64 Creatinine (mg/dl) 0.84 (0.18) 0.82 (0.20) 0.60 Data are presented as mean (SD), median (interquartile change) or n (%). a The Fisher’s exact test. Other categorical P-values are from the χ2 test. ACEI: angiotensin-converting enzyme inhibitor; AF: atrial fibrillation; AVA: aortic valve area; BMI: body mass index; CAD: coronary artery disease; CVD: cerebrovascular disease; COPD: chronic obstructive pulmonary disease; LVEF: left ventricular ejection fraction; MI: myocardial infarction; NYHA: New York Heart Association; PAD: peripheral artery disease; PASP: pulmonary artery systolic pressure; SD: standard deviation; TMPG: transaortic mean pressure gradient. Table 1: Preoperative variables for those with bendopnea and without bendopnea Without bendopnea (n = 62) With bendopnea (n = 46) P-value Age (years) 75 (4) 74 (3) 0.23 Male 46 (74) 28 (61) 0.14 BMI (kg/m2) 26.40 (2.64) 26.15 (4.19) 0.29 Comorbidities  Hypertension 13 (21) 13 (28) 0.38  Diabetes mellitus 14 (22) 9 (19) 0.70  Smoking 14 (22) 8 (17) 0.50  Hyperlipidaemia 18 (29) 10 (21) 0.39  COPD 11 (17) 3 (6) 0.08  Previous CVD 2 (3) 2 (4) 1a  Previous PAD 5 (8) 3 (6) 1a  Previous MI 11 (17) 9 (19) 0.80  Permanent AF 16 (26) 5 (11) 0.05 CAD 1a  None 50 (81) 38 (83)  1-Vessel 8 (13) 6 (13)  2-Vessel 3 (5) 2 (4)  3-Vessel 1 (1) 0 (0) Echocardiographic variables  LVEF (%) 59 (9) 58 (7) 0.55  AVA (cm2) 0.76 (0.13) 0.66 (0.16) 0.0006  PASP (mmHg) 40 (11) 51 (11) <0.001  TMPG (mmHg) 48 (6) 53 (7) 0.00005 Medications  ACE inhibitor 45 (72) 39 (84%) 0.13  Angiotensin receptor blocker 17 (27) 7 (15%) 0.13  Aldosterone antagonist 39 (63) 25 (54) 0.37  Beta-blocker 50 (80) 37 (80) 0.97  Furosemide 62 (100) 46 (100) 1.0  Aspirin 24 (38) 23 (50) 0.24  HMG-CoA reductase inhibitors 57 (92) 42 (91) 1a NYHA classification <0.0001  Class I 0 (0) 0 (0)  Class II 35 (56) 4 (9)  Class III 23 (37) 26 (56)  Class IV 4 (7) 16 (35) Estimated haemodynamic profile 0.0004a  A 31 (50) 7 (15)  B 23 (37) 22 (48)  C 6 (10) 14 (30)  L 2 (3) 3 (7) EuroSCORE surgical mortality risk (%) 1.6 (1.2–1.9) 1.6 (1.3–2.3) 0.15 Cardiopulmonary bypass time (min) 52 (8) 51 (8) 0.5 Haemoglobin (g/dl) 14.20 (1.50) 14.44 (1.28) 0.64 Creatinine (mg/dl) 0.84 (0.18) 0.82 (0.20) 0.60 Without bendopnea (n = 62) With bendopnea (n = 46) P-value Age (years) 75 (4) 74 (3) 0.23 Male 46 (74) 28 (61) 0.14 BMI (kg/m2) 26.40 (2.64) 26.15 (4.19) 0.29 Comorbidities  Hypertension 13 (21) 13 (28) 0.38  Diabetes mellitus 14 (22) 9 (19) 0.70  Smoking 14 (22) 8 (17) 0.50  Hyperlipidaemia 18 (29) 10 (21) 0.39  COPD 11 (17) 3 (6) 0.08  Previous CVD 2 (3) 2 (4) 1a  Previous PAD 5 (8) 3 (6) 1a  Previous MI 11 (17) 9 (19) 0.80  Permanent AF 16 (26) 5 (11) 0.05 CAD 1a  None 50 (81) 38 (83)  1-Vessel 8 (13) 6 (13)  2-Vessel 3 (5) 2 (4)  3-Vessel 1 (1) 0 (0) Echocardiographic variables  LVEF (%) 59 (9) 58 (7) 0.55  AVA (cm2) 0.76 (0.13) 0.66 (0.16) 0.0006  PASP (mmHg) 40 (11) 51 (11) <0.001  TMPG (mmHg) 48 (6) 53 (7) 0.00005 Medications  ACE inhibitor 45 (72) 39 (84%) 0.13  Angiotensin receptor blocker 17 (27) 7 (15%) 0.13  Aldosterone antagonist 39 (63) 25 (54) 0.37  Beta-blocker 50 (80) 37 (80) 0.97  Furosemide 62 (100) 46 (100) 1.0  Aspirin 24 (38) 23 (50) 0.24  HMG-CoA reductase inhibitors 57 (92) 42 (91) 1a NYHA classification <0.0001  Class I 0 (0) 0 (0)  Class II 35 (56) 4 (9)  Class III 23 (37) 26 (56)  Class IV 4 (7) 16 (35) Estimated haemodynamic profile 0.0004a  A 31 (50) 7 (15)  B 23 (37) 22 (48)  C 6 (10) 14 (30)  L 2 (3) 3 (7) EuroSCORE surgical mortality risk (%) 1.6 (1.2–1.9) 1.6 (1.3–2.3) 0.15 Cardiopulmonary bypass time (min) 52 (8) 51 (8) 0.5 Haemoglobin (g/dl) 14.20 (1.50) 14.44 (1.28) 0.64 Creatinine (mg/dl) 0.84 (0.18) 0.82 (0.20) 0.60 Data are presented as mean (SD), median (interquartile change) or n (%). a The Fisher’s exact test. Other categorical P-values are from the χ2 test. ACEI: angiotensin-converting enzyme inhibitor; AF: atrial fibrillation; AVA: aortic valve area; BMI: body mass index; CAD: coronary artery disease; CVD: cerebrovascular disease; COPD: chronic obstructive pulmonary disease; LVEF: left ventricular ejection fraction; MI: myocardial infarction; NYHA: New York Heart Association; PAD: peripheral artery disease; PASP: pulmonary artery systolic pressure; SD: standard deviation; TMPG: transaortic mean pressure gradient. Patients with bendopnea versus patients without bendopnea were more impaired as assessed by NYHA functional class. There was also a difference in estimated haemodynamic profiles between those with bendopnea and those without bendopnea. Specifically, the vast majority of those without bendopnea were classified in haemodynamic Profiles A (50%) or B (37%), whereas the vast majority of those with bendopnea were classified as haemodynamic Profiles B (48%) and C (30%). As assessed by echocardiography, patients with bendopnea had higher pulmonary artery systolic pressures (P < 0.0001), smaller AVAs (P = 0.0006) and higher transaortic mean pressure gradient (P < 0.001), but there was no difference in left ventricular ejection fraction between the two groups whether or not left ventricular ejection fraction was analysed as a continuous (P = 0.55) or categorical (P = 0.4) variable. The postoperative characteristics of subjects with bendopnea and without bendopnea are summarized in Table 2. There was a numerically higher rate of in-hospital mortality in those with bendopnea compared to those without bendopnea, although this difference did not reach statistical significance. In-hospital mortality was due to organ failure and cardiopulmonary bypass-related systemic inflammatory response syndrome. There was also a trend towards higher rate of 30-day postoperative mortality in those with bendopnea. Patients with bendopnea had longer duration of mechanical ventilation and length of stay in the hospital. Table 2: Postoperative variables for patients with bendopnea and patients without bendopnea Without bendopnea (n = 62) With bendopnea (n = 46) P-value In-hospital mortality 2 (3) 6 (13) 0.07a 30-Day postoperative mortality 3 (5) 8 (17) 0.05a Duration of mechanical ventilation (h) 13.5 (10–16) 18 (12–23) 0.004 Length of stay in the hospital (days) 9 (8–10) 11 (8–12) 0.009 Without bendopnea (n = 62) With bendopnea (n = 46) P-value In-hospital mortality 2 (3) 6 (13) 0.07a 30-Day postoperative mortality 3 (5) 8 (17) 0.05a Duration of mechanical ventilation (h) 13.5 (10–16) 18 (12–23) 0.004 Length of stay in the hospital (days) 9 (8–10) 11 (8–12) 0.009 Data are presented as mean (SD), n (%) or median (25th–75th percentile). a The Fisher’s exact test. Table 2: Postoperative variables for patients with bendopnea and patients without bendopnea Without bendopnea (n = 62) With bendopnea (n = 46) P-value In-hospital mortality 2 (3) 6 (13) 0.07a 30-Day postoperative mortality 3 (5) 8 (17) 0.05a Duration of mechanical ventilation (h) 13.5 (10–16) 18 (12–23) 0.004 Length of stay in the hospital (days) 9 (8–10) 11 (8–12) 0.009 Without bendopnea (n = 62) With bendopnea (n = 46) P-value In-hospital mortality 2 (3) 6 (13) 0.07a 30-Day postoperative mortality 3 (5) 8 (17) 0.05a Duration of mechanical ventilation (h) 13.5 (10–16) 18 (12–23) 0.004 Length of stay in the hospital (days) 9 (8–10) 11 (8–12) 0.009 Data are presented as mean (SD), n (%) or median (25th–75th percentile). a The Fisher’s exact test. In univariable analysis, the association of bendopnea with in-hospital mortality did not reach statistical significance [odds ratio (OR) 4.5, 95% confidence interval (CI) 0.88–23.42; P = 0.07], but the association with 30-day postoperative mortality was significant (OR 4.2, 95% CI 1.05–16.9; P = 0.04). Bendopnea was associated with duration of mechanical support (regression coefficient 4.0, t = 3.2, P = 0.002) and length of stay in the hospital (regression coefficient 1.5, t = 2.7, P = 0.007). In multivariable analysis, only bendopnea (OR 10.1, 95% CI 1.6–64.6; P = 0.02) and age (OR 1.4, 95% CI 1.007–1.833; P = 0.05) were associated with an increased risk of in-hospital mortality, but no variables were associated with 30-day postoperative mortality. Bendopnea was also associated with duration of mechanical ventilation (parameter estimate 4.5, P = 0.0009) and length of stay in the hospital (parameter estimate 2.4, P < 0.0001). There were no other variables that were significant for duration of mechanical ventilation. The only other variables associated with length of stay in the hospital were estimated haemodynamic Profile L (parameter estimate −3.7, P = 0.003) and echocardiographic transaortic mean pressure gradient (parameter estimate −0.11, P = 0.01). DISCUSSION To our knowledge, this is the first study demonstrating that bendopnea was common and associated with adverse outcomes following SAVR in patients with severe AS. Specifically, we found that 42% of subjects with severe AS had bendopnea and that this symptom was associated with higher pulmonary artery pressures and a smaller AVA and was associated with increased risk of adverse outcomes following SAVR including a longer duration of mechanical ventilation and length of stay in the hospital. These data suggest that bendopnea provides prognostic information in the patients with severe symptomatic AS referred for AVR. Degenerative AS could be viewed as a disease with a silent phase of sclerosis and calcification of the valve, followed by progression of AS severity with different grades of left ventricular involvement. Once the AS is classified as severe, patients develop symptoms at different stages of the disease process [14]. The physical examination is essential in the diagnosis and management of patients with AS. Increased ventricular filling pressures in these patients lead to congestive symptoms that cause decompensated HF and hospital admissions [14]. We found that bendopnea was present in a sizeable minority (42%) of patients with severe symptomatic AS admitted in our centre. Previous studies have demonstrated a prevalence between 18% and 48% in populations of HF [6–9]. There are several novel aspects of our study. This is the first study that assessed the prevalence and prognostic value of bendopnea in patients with valvular heart disease (specifically AS). Second, the association of bendopnea with subsequent risk of adverse outcome following cardiac surgery (length of stay in the hospital, longer mechanical ventilation and possibly mortality) has not been demonstrated previously. The duration of mechanical ventilation is one of the most important clinical factors which predict outcomes in cardiac surgery [15]. The duration of mechanical ventilation is also associated with pulmonary venous hypertension [16]. In our study, patients with bendopnea had a longer duration of the mechanical ventilation. Given that bendopnea was associated with an elevated pulmonary capillary wedge pressure [6], an important contributor to secondary pulmonary hypertension [17], it may not be surprising that bendopnea is associated with an increased duration of mechanical ventilation. Clinicians often need to identify patients who are likely to require a longer period of high dependency care after cardiac surgery to allow for appropriate preoperative planning [18], especially because prolonged intensive care unit and ward stay in patients undergoing cardiac surgery increases overall hospital costs [19, 20]. Our data suggest that an assessment for bendopnea, an easily performed and inexpensive test, might assist in this manner. Previously, NYHA functional class was found to be an independent predictor of length of stay in the hospital [21]. Such data are supportive of the plausibility of an association of bendopnea with length of stay in the hospital, given that bendopnea itself has been shown to be associated with advanced NYHA functional class [9]. Limitations Our study has limitations. This was a single-centre study; thus, the results may not be generalizable. As described, 20 subjects were excluded from analysis, and this too may impact generalizability. Also, we did not systematically evaluate the factors which led physicians to retain a patient longer in the hospital. It is known that length of stay in the hospital may be influenced by non-medical determinants [22]. For example, we did not collect potential social reasons for delay in hospital discharge, although that would not expect to be associated with bendopnea status. Our sample size was small as was our event rates of in-hospital mortality and 30-day postoperative mortality, which may have impacted the robustness of the associations with clinical postoperative variables. Nevertheless, these data suggest that bendopnea was a prognostic marker in the patients with severe symptomatic AS referred for AVR, though we recognize further validation studies are needed. Finally, we also tested a number of outcomes, thus increasing the chance of false associations. CONCLUSION Bendopnea was present in a sizeable minority of patients with severe symptomatic AS referred for SAVR. Furthermore, bendopnea was associated with preoperative higher pulmonary pressures and smaller AVAs, as well as increased postoperative duration of mechanical ventilation and overall length of stay in the hospital. Together these data suggest that bendopnea provides prognostic information in patients with severe AS and that the healthcare provider caring for patients with severe AS should be aware of this novel symptom. Conflict of interest: none declared. REFERENCES 1 Kennedy KD , Nishimura RA , Holmes DR Jr , Bailey KR. Natural history of moderate aortic stenosis . J Am Coll Cardiol 1991 ; 17 : 313 – 9 . Google Scholar CrossRef Search ADS PubMed 2 Kitai T , Honda S , Okada Y , Tani T , Kim K , Kaji S et al. Clinical outcomes in non-surgically managed patients with very severe versus severe aortic stenosis . Heart 2011 ; 97 : 2029 – 32 . Google Scholar CrossRef Search ADS PubMed 3 Chizner MA , Pearle DL , deLeon AC Jr. The natural history of aortic stenosis in adults . 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Journal

Interactive CardioVascular and Thoracic SurgeryOxford University Press

Published: Jun 2, 2018

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