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Management of Symptomatic Severe Aortic Stenosis in Patient With Very Severe Chronic Obstructive Pulmonary Disease
Author’s Accepted Manuscript Management of Symptomatic Severe Aortic Stenosis in Patient with very Severe Chronic Obstructive Pulmonary Disease Amgad Mentias, Nadeen N Faza, Mohammad Q. Raza, Ali Malik, Jasneet Devgun, L. Leonardo Rodriguez, Stephanie Mick, Jose L. Navia, Eric E. Roselli, Paul Schoenhagen, Lars G. Svensson, E Murat Tuzcu, Amar Krishnaswamy, Samir R. Kapadia
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To appear in: Seminars in Thoracic and Cardiovascular Surgery Accepted date: 31 August 2016 Cite this article as: Amgad Mentias, Nadeen N Faza, Mohammad Q. Raza, Ali Malik, Jasneet Devgun, L. Leonardo Rodriguez, Stephanie Mick, Jose L. Navia, Eric E. Roselli, Paul Schoenhagen, Lars G. Svensson, E Murat Tuzcu, Amar Krishnaswamy and Samir R. Kapadia, Management of Symptomatic Severe Aortic Stenosis in Patient with very Severe Chronic Obstructive Pulmonary D i s e a s e , Seminars in Thoracic and Cardiovascular Surgery, http://dx.doi.org/10.1053/j.semtcvs.2016.08.013 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
-Original researchManagement of Symptomatic Severe Aortic Stenosis in Patient with very Severe Chronic Obstructive Pulmonary Disease Amgad Mentias*, Nadeen N Faza *, Mohammad Q. Raza, Ali Malik, Jasneet Devgun, L. Leonardo Rodriguez, Stephanie Mick, Jose L. Navia, Eric E. Roselli, Paul Schoenhagen, Lars G. Svensson, E Murat Tuzcu, Amar Krishnaswamy and Samir R. Kapadia From the Heart and Vascular Institute, Cleveland Clinic, Ohio, USA. * Co-first authors. Both authors contributed equally to the work
Word Count: 4100 Funding: no funding was provided for this work. Disclosure: Dr. Eric Roselli: CONSULTANT FEES/HONORARIA - Bolton, Cook, Edwards Lifesciences, Gore, MEDTRONIC, Sorin, St Jude, Terumo. Remaining of authors has nothing to disclose.
Corresponding Author Samir R Kapadia, MD Professor of Medicine Director, Sones Cardiac Catheterization Laboratories Department of Cardiovascular Medicine, J2-3 Heart and Vascular Institute Cleveland Clinic 9500 Euclid Avenue Cleveland, OH 44195 Tel. 216-444-6735 Fax. 216-445-6176 Email: [email protected]
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Abstract Background: Transcatheter Aortic Valve Replacement (TAVR) is a viable option for patients with severe Chronic Obstructive Pulmonary Disease (COPD) who are deemed inoperable or high risk for surgery. We sought to determine outcomes of patients with severe aortic stenosis (AS) and severe COPD referred for AVR. Methods: 131 patients with Severe AS and severe COPD (Gold criteria) were evaluated at our center between 2008 -2013 and were divided retrospectively into 4 groups: 1- medical management, 2- balloon aortic valvuloplasty, 3- surgical aortic valve replacement and 4- TAVR. Baseline, clinical, and echo data were recorded. Primary outcome was cardiovascular death. Results: From the study cohort 54(41.2%), 29(22.1%), 21 (16.0%), and 27 (20.6%) were included in groups 1-4 respectively. Age was 74.9±8.8, 76.2 ± 8.8, 78.8 ± 7.4 and 82.8 ± 6.8 years respectively (P <0.01). There was no significant difference between groups in hypertension, diabetes, aortic valve area or gradients, forced expiratory volume in first second, right ventricular systolic pressure, ejection fraction, and STS score. At 3±1.5 years, death occurred in 87%, 97%, 47.7% and 51.8% of patients respectively. Heart failure (HF) readmissions occurred in 43%, 42%, 9.6% and 14.8% respectively. When SAVR and TAVR groups were compared, there was no significant difference in survival (P=0.719) or HF readmissions (P=0.19). Conclusion: In severe/very severe COPD and Severe AS patients, replacing the severely stenotic aortic valve either by Surgical AVR or TAVR improves survival and reduces re-hospitalization compared to medical therapy or BAV. Keywords: Aortic valve stenosis, COPD, TAVR, Surgical aortic valve replacement.
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List of Abbreviations: AS: Aortic stenosis AV: Aortic valve AVA: Aortic valve area AVR: Aortic valve replacement BAV: Balloon aortic valvuloplasty CAD: Coronary artery disease COPD: Chronic pulmonary obstructive disease DI: Dimensionless index EF: Ejection fraction FEV1: Forced expiratory volume in first second FVC: Forced vital capacity TAVR: Transcatheter aortic valve replacement MPG: Mean pressure gradient NYHA: New York Heart association PFT: Pulmonary function testing PPG: Peak pressure gradient RVSP: Right ventricular systolic pressure STS: The Society of Thoracic Surgeons TEE: Transesophageal echocardiography
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Perspective: COPD increases mortality of aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Here, we compare outcomes in symptomatic severe AS patients with very severe COPD referred for surgical AVR versus TAVR. After follow up of 3 years, there was no difference in short and long-term mortality between both groups. On multivariate analysis, TAVR and surgical AVR both improved survival.
Central message: In severe COPD and AS, replacing the AV either by surgical AVR or TAVR improves survival and reduces re-hospitalization equally.
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Introduction: Aortic stenosis (AS) is the most common valvular disease among the elderly population in the United States. In patients older than 65 years, the prevalence of symptomatic aortic stenosis is 4%1, and the prevalence is expected to grow as average life expectancy increases. Given its dismal natural course, once aortic stenosis is symptomatic the only effective treatment is aortic valve replacement2. The introduction of transcatheter aortic valve replacement (TAVR) has revolutionized the management of patients with AS, and is considered a viable option in high-risk and inoperable patients3,4. Medical management does not provide a mortality benefit in the management of symptomatic severe AS, and is used primarily to palliate patients who do not qualify for TAVR or Surgical AVR5. Lastly, percutaneous balloon aortic valvuloplasty (BAV) may be used as a palliative strategy, to better discern the contribution of aortic valve disease to functional decline in patients with competing comorbidities, or as a bridging measure for patients temporarily unable to undergo definitive therapy with Surgical AVR or TAVR6–9.Patients with AS are usually elderly and present with multiple major comorbidities. Chronic obstructive pulmonary disease (COPD) is the third leading cause of morality in the United States, its incidence increases with age10, and accordingly is diagnosed in up to 20% of patients presenting for Surgical AVR and 20-40% of patients presenting for TAVR.4,11,12 The Presence of COPD in patients undergoing Surgical AVR is significantly associated with a higher incidence of postoperative pneumonia, in addition to worse in-hospital and long-term mortality13–15. In the TAVR population, COPD is an independent predictor of in-hospital and long-term mortality16–18. Previous reports have studied outcomes of COPD patients undergoing TAVR and COPD patients
5
undergoing Surgical AVR
13,19
, but none of the previous studies have discussed approach with
different treatment strategies in this high risk population. The aim of our study was to determine outcomes in high-risk, symptomatic AS patients with severe/very severe COPD referred for multispecialty evaluation by a high risk AVR team and who ultimately were decided to undergo TAVR, Surgical AVR, BAV, or continued medical therapy.
Methods: As a part of a retrospective cohort study, we studied 131 patients who presented to our institution between March 2008 to September 2013 for high risk AVR evaluation with severe symptomatic aortic stenosis and severe or very severe chronic obstructive pulmonary disease (COPD) as classified by Gold criteria (Table 1). All patients were assessed by a high risk AVR team to determine eligibility for aortic valve replacement. Inclusion criteria in addition to diagnosis of COPD as above were: severe (AS) as defined by aortic valve area ≤ 0.8 cm2, mean pressure gradient ≥ 40 mmHg, or peak velocity across aortic valve ≥ 4 m/sec. All patients had symptomatic AS with NYHA class II or higher. Exclusion criteria were as follows: bicuspid aortic valve, history of aortic valve surgery, severe left ventricular dysfunction with EF ≤ 15%, history of myocardial infarction or stroke in the previous 6 months, severe mitral or aortic regurgitation. Baseline demographic characteristics, clinical status, and echocardiographic parameters were recorded in the first encounter. The Society of Thoracic Surgeons predicted risk of mortality score (STS) was calculated for all patients using the STS Adult Cardiac Surgery Risk Calculator. After evaluation by the high risk AVR team, patients underwent 1) Medical management 2) BAV 3) Surgical AVR or 4) TAVR.
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All procedures and data collection were approved and monitored by the Cleveland Clinic Institutional Review Board (IRB) with waiver of individual informed consent. Echocardiography: A comprehensive Doppler echocardiographic evaluation was performed at the time of initial presentation according to the American Society of Echocardiography guidelines using commercially available instruments (Philips Medical Systems, NA, Bothell, WA; General Electric Medical Systems, Milwaukee, WI; and Siemens Medical Solutions USA, Inc, Malvern,PA). Left ventricular ejection fraction (EF), LV end systolic and end-diastolic volumes, left atrial dimensions, left ventricular diastolic function, left ventricular wall thickness and right ventricular systolic pressures (RVSP) were recorded. Aortic stenosis severity was assessed by calculating mean and peak pressure gradients according to modified Bernoulli equation, aortic valve area (AVA) by continuity equation, and dimensionless index (DI) using standard guidelines 20. Transcatheter aortic valve replacement: Patients who were determined as inoperable or at high-risk for surgical complications by the high risk AVR team underwent TAVR. The default approach to TAVR in patients with adequate iliofemoral access was transfemoral (TF); those patients for whom TF access was not possible on the basis of CT-analysis underwent alternative access (transapical or transaortic). All TAVR procedures were performed in hybrid operating rooms under general anesthesia and with guidance of transesophageal echocardiography (TEE). The Edwards SAPIEN valve series (9500 TFX and SAPIEN XT; Edwards Lifesciences, Irvine, CA) was used in all patients who underwent TAVR.
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Balloon aortic valvuloplasty (BAV) Patients who were deemed inoperable or high-risk and did not undergo TAVR due to peripheral arterial disease, annulus size, unclear contribution of AS to functional decline due to comorbid conditions, or patient desire underwent BAV. This was performed via the standard retrograde approach using Z-med II balloons (B. Braun Medical Inc, Bethlehem, PA) sized according to left-ventricular outflow tract dimension and hemodynamic response. COPD assessment Pulmonary function testing was performed in our institution’s pulmonary function lab. All testing results were reviewed by an attending pulmonologist. COPD severity was defined by Gold Criteria (Table 1), and only patients with severe or very severe COPD [Forced expiratory volume in 1st second/Forced vital capacity (FEV1/FVC) ≤ 0.70 and FEV1 ≤ 50% predicted value] were included. Data pertaining to long-term oral corticosteroid therapy and home oxygen use was recorded. Follow up and outcomes: Patients were followed for a median of 3.0±1.5 years. Length of hospital stay and postoperative complications including prolonged intubation, re-intubation, stroke/transient ischemic attack and major bleeding requiring blood transfusion within the first 30 days were recorded for patients undergoing TAVR, Surgical AVR, BAV, and medical management. The primary outcome was all-cause mortality and secondary outcomes included immediate post-intervention respiratory complications such as prolonged intubation (defined as intubation for more than 24 hours); hospital readmission for COPD or heart failure, pneumonia, or respiratory failure; and new-onset home oxygen use.
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Statistical analysis Continuous variables are expressed as mean ± standard deviation (SD), or median and inter-quartiles for skewed distributions, and compared using the Student t-test or ANOVA (for normally distributed variables) or the Wilcoxon test (for non‐normally distributed variables). Categorical data is expressed as a percentage and compared using Fisher exact or Chi-Square test. To assess outcomes, Cox proportional hazards analysis was performed to assess independent predictors of outcome (using a P-value cutoff of < 0.05 for statistical significance). Hazard ratios (HRs) with 95% confidence intervals were calculated and reported. Cumulative proportion of events as a function over time was obtained by the Kaplan‐Meier method to do the survival analysis. Statistical analysis was performed using JMP pro version 10.0.
Results: Baseline characteristics of the patients in each group are shown in table 2. Baseline echocardiography and pulmonary functions testing characteristics for patients in the four groups are shown in table 3. The mean age for the TAVR group was significantly greater than the three remaining groups (p = 0.0007). There were no significant differences between the four groups with respect to comorbid conditions, severity of AS, severity of COPD by PFT, or STS score at baseline. Five patients (18.5%) underwent TAVR through the transapical approach and the remaining underwent TF-TAVR. After follow up of 3 ± 1.5 years, the primary outcome of cardiovascular death occurred in 87%, 97%, 47.7% and 51.8% of patients in the four groups, respectively (p < 0.0001). The secondary outcomes of heart failure, respiratory failure, and COPD exacerbation 30 days readmissions occurred in 43%, 42%, 9.6% and 14.8% of patients, respectively (p = 0.016). 9
When comparing group 3 (Surgical AVR) and 4 (TAVR) only, the TAVR group was older (P=0.005), but there was no significant difference in sex (p = 0.3), smoking (p = 0.7), hyperlipidemia (p = 0.6), renal impairment (p = 0.6), hypertension (p = 0.2), history of stroke (p = 0.1), Coronary artery disease (p = 0.3), New York Heart Association (NYHA) class (p = 0.3), need for home oxygen (p = 0.7), STS score (p = 0.8), baseline left ventricular EF (p = 0.5), mean AV PG (p = 0.8), AVA (p = 0.3), RVSP (p = 0.2), FEV1% (p = 0.2) or FEV1/FVC (p = 0.6). The median length of hospital stay post-intervention was significantly longer for the surgical group (17.8 days, IQs 8.9-23.7 days) compared to the TAVR group (7.4 days, IQs 3.211.8 days) (p = 0.01). Prolonged intubation (> 24 hours) occurred in 47.6% and 14.8% of the SAVR and TAVR groups, respectively (p = 0.01). Tracheostomy was required in three (14.3%) and two (7.5%) patients in the Surgical AVR and TAVR groups, respectively (p = 0.6). Thirtyday mortality occurred in two (9.5%) patients in the surgical group and three (11.2%) patients in the TAVR group (p = 0.6). When the two patients who underwent BAV then TAVR were included in the TAVR group for analysis, there was still no difference in 30-day mortality between the two groups (9.5% vs. 9%, p=0.9) Follow up was completed in majority of the patients (98.5% overall in the study population, 96.3% in the TAVR group, and 95.2% in the surgical AVR group). EF, RVSP and functional status was assessed and reported from the last available follow up. Patients who underwent Surgical AVR had significant improvement in RVSP from 47 mmHg at baseline to 39 mmHg (p=0.01) in follow up, while RVSP did not show significant change in TAVR group. There was no significant change in EF before and after procedure in both groups (Figure 2). Patients in both groups showed significant improvement in functional class after the procedure, p<0.001. There was no difference in degree of improvement between TAVR and SAVR. P=NS. Data regarding 10
home oxygen use after the procedure was lacking for majority of the study sample, so it was not reported nor included in the analysis. Aortic regurgitation grade ≥ 2 at follow up was found in one (4.8%) and four (14.8%) patients in the Surgical AVR and TAVR groups, respectively. Post-procedural stroke occurred in one patient from each group, heart failure and COPD admissions in follow-up occurred in two (9.5%) and four patients (14.8%) in the Surgical AVR and TAVR groups (p=0.1), respectively. The primary outcome of all-cause mortality occurred in 47.7 and 51.8% (p = 0.7) of the patients in each group, respectively. When the two patients who crossed from BAV to TAVR arm were included in the final analysis, there was still no difference in mortality between both groups (47.7% vs 48.3%, p=0.9). On multivariable analysis, after adjusting for age and other predictors of worse outcomes, Surgical AVR or TAVR procedure both improved survival significantly (p = 0.12; OR 3.79, 95% CI: 0.70-20.49). Apart from age and gender, all other variables with p-value for difference between the two groups < 0.2 were included in the regression model for multivariable analysis. The Kaplan‐Meier curve showing long‐term outcomes in the four groups is shown in figure 3. Discussion Our study demonstrates that TAVR is similar to surgical AVR with respect to intermediate-term survival in patients with severe symptomatic AS and severe or very severe COPD. We also demonstrate in our analysis that TAVR in this population is associated with shorter hospital stay and less postoperative respiratory complications (including need for prolonged intubation) with similar rates of hospital readmission. COPD is a major limiting factor in patient selection for surgical intervention; this explains the higher prevalence of COPD in patients undergoing TAVR versus Surgical AVR in our group and other series’ 4,11,12. 11
The importance of chronic lung disease (CLD) in patients undergoing TAVR has been demonstrated by other investigators. Dvir and colleagues evaluated the impact of CLD on the outcomes of TAVR in 2500 patients. CLD was associated with higher mortality after one year compared to patients without CLD (23.4% vs. 19.6%, p = 0.02). In the same study, it was demonstrated that in patients with CLD and severe AS, TAVR and SAVR had comparable outcomes and is better than standard medical therapy. However, in contrast to our study, they did not specifically evaluate patients with COPD as opposed to other lung diseases.21 Mok and colleagues19 evaluated the outcomes of TAVR in COPD patients, though only 29.5% of their study population had COPD. In contrast, our entire study population included patients with significant COPD. More importantly, our study population had more severe and advanced COPD with a mean FEV1 of 37.8± 9.9% in comparison to an FEV1 of 60 ± 21% in the afore-mentioned study. This may partially explain the numerically worse survival in our group in comparison to that in the study by Mok and colleagues (48.2 vs 70.6%). In the analysis by Gunter and colleagues, COPD was not found to be significant predictor of in-hospital mortality, but was shown to be a strong incremental predictor of long-term mortality after Surgical AVR13. Three-year survival in severe COPD patients after SAVR was reported to be 63.5% compared to 52.2% in our study. They also demonstrated that COPD was a predictor of postoperative pneumonia, but failed to predict postoperative prolonged ventilation. Similarly, Spoon and colleagues
22
studied 41 patients with severe/very severe COPD who
underwent surgical AVR. 30-day mortality was reported as 4.9% (2 patients) compared with 9.5% (2 patients) in our study. Five-year survival for this group in that study was 52% compared to the 52% 3-year survival in our study.
12
Our study reveals that COPD patients undergoing Surgical AVR had a significantly higher incidence of prolonged intubation than those who underwent TAVR. This finding is consistent with a study by Thourani and colleagues23 who reported that preoperative severe COPD was only second to renal failure as an organ-specific poor prognostic factor in terms of survival after Surgical AVR. To our knowledge, this is the first study to compare outcomes of surgical AVR to TAVR in a single center in severe/very severe COPD patients. As such, we believe it contributes to the body of literature discussed above regarding patients with lung disease undergoing an AVR procedure. As the patient population referred for TAVR continues to expand, it is important to understand how comorbid conditions such as COPD should be considered in patient selection with respect to post-procedural outcomes including pulmonary complications. In this regard, it appears that patients with significant COPD fare better with TAVR than with Surgical AVR. As we move toward performing more TF-TAVR procedures without endotracheal intubation, we hypothesize that this separation in pulmonary outcomes would only increase and would be an important area for further investigation 24. Study limitations: Our study included a relatively small number of patients in each group which makes it underpowered. This is partly due to the fact that our inclusion criteria were strict to patients with severe/very severe COPD. Another limitation stems from the fact that this is a retrospective, single center study which might pose a selection bias and findings from this study might not be generalizable to other surgical centers. In addition, it has been reported that pulmonary function tests might overestimate COPD severity in patients with concomitant aortic stenosis patients25. Unfortunately, post-intervention pulmonary function testing were not available for comparison to 13
baseline pulmonary function testing to better evaluate the effect of aortic valve intervention on patients’ respiratory status. Our study is the first to compare outcomes of different management modalities in patients with severe aortic stenosis and severe COPD. Additional prospective studies are needed to better evaluate the effect of these management modalities, especially with the increasing use of TAVR as a viable, similar and less invasive treatment modality for severe aortic stenosis.
Conclusion: Transcatheter aortic valve replacement is similar to surgical aortic valve replacement for patients with severe aortic stenosis and severe/very severe COPD regarding long term survival, and offers shorter hospital stay with less postoperative respiratory complications.
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Magee MJ, Herbert MA, Roper KL, et al. Pulmonary function tests overestimate chronic pulmonary disease in patients with severe aortic stenosis. Ann Thorac Surg. 2013;96(4):1329-1335. doi:10.1016/j.athoracsur.2013.04.123.
Figure 1: Flow chart of study population enrollment. Figure 2: Panel A: Incidence of postoperative complications between Surgical AVR and TAVR groups. CHF: congestive heart failure, COPD: chronic obstructive pulmonary disease, Panel B: Change in functional status at follow up. NYHA: New York Heart Association. Patients in both groups showed significant improvement in functional class after the procedure, p<0.001. Figure 3: Kaplan‐Meier curve showing survival in severe AS and very severe COPD managed by TAVR, Surgical AVR, BAV and medical therapy (p=<00.1 between all groups) (p=NS between TAVR and Surgical AVR)
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Table 1 Gold's criteria for COPD severity. FEV1 forced expiratory volume in first second, FEV1/FVC forced expiratory volume in first second/forced vital capacity. Stage I Stage II Stage III Stage IV
Mild COPD Moderate COPD Severe COPD Very Severe COPD
FEV1/FVC<0.70 FEV1/FVC<0.70 FEV1/FVC<0.70 FEV1/FVC<0.70
FEV1≥ 80% normal FEV1 50-79% normal FEV1 30-49% normal FEV1 <30% normal
Table 2 Baseline characteristics for patients in the four groups. PVD peripheral vascular disease, CABG coronary artery bypass grafting. PCI: percutaneous coronary intervention. NYHA: New York Heart Association. STS Society of Thoracic Surgeons. BAV: balloon aortic valvulopasty. Variable Number Age (year) Sex (males) BMI (kg/m2) Smoking Diabetes mellitus Hyperlipidemia Renal impairment Hypertension History of stroke Pulmonary hypertension PVD Home oxygen History of CABG Prior PCI NYHA II NYHA III NYHA IV STS score
Medical 54 74.9±8.8, 46% 28.3±9.1 79.6% 46.3% 81.5% 29.6% 79.6% 11.1% 33.3% 46.3% 50% 40% 33% 3.7% 77.8% 16.7% 10.9±7.1
BAV 29 78.8 ± 7.4 44.8% 27.7±9.3 69%, 38% 65.5% 20.7% 75.9% 0% 34.5% 10.3% 51.7% 20.7% 24.1% 6.9% 65.5% 27.6% 10.3±6.7
Surgical AVR 21 76.2 ± 8.8 66.7% 28.2±9.4 85.7% 38.1% 81% 38.1% 76.2% 14.3% 47.6% 52.4% 33.3% 42.9% 28.6% 9.5% 52.4% 38.1% 11.4±5.9
TAVR 27 82.8 ± 6.8 81.5% 26.2±5.6 77.8% 37% 88.9% 37% 92.6% 37% 48.2% 33.3% 25.9% 44.4% 25.9% 11.1% 70.4% 18.5% 11.2±4.8
P value 0.0007* 0.008* 0.7791 0.54 0.81 0.17 0.49 0.29 0.004* 0.46 0.002* 0.1 0.23 0.87
0.93
18
Table 3 Baseline echocardiography and pulmonary functions testing for patients in the four groups. EF Ejection fraction. PPG peak pressure gradient. MPG mean pressure gradient. AVA aortic valve area. RVSP right ventricular systolic pressure. Variable EF (%) PPG (mmHg) MPG (mmHg) AVA (cm2) RVSP (mmHg) FEV1/FVC FEV1% FEV1 FVC
Medical 45.7±16.4 68±27.6 40.1±17.7 0.65±0.2 52±19.9 50.7±12.2 36.6±10.7 0.85±0.27 0.5±0.12
BAV 44.5±17.1 82.3±30.9 49.6±18.9 0.61±0.2 46.6±12.7 49.4±12.1 37.4±10.6 0.81±0.26 0.49±1.2
Surgical AVR 45±16.5 83.5±28.1 47.9±19.5 0.61±0.2 46.6±12.7 49.4±12.1 38±7.1 1.04±0.29 0.47±0.12
TAVR 48.7±13.5 76.2±27.3 44.8±16.3 0.64±0.1 42.7±13 49±12.7 40.6±8.9 1.05±0.28 0.5±0.13
P value 0.76 0.087 0.11 0.71 0.18 0.74 0.39 0.05 0.4
Table 4: Comparison of outcomes after Surgical AVR versus TAVR in patients with severe/very severe COPD Outcome Length of hospital stay: Median (IQs) Prolonged intubation >24 hours Median intubation time (IQs) Tracheostomy Aortic regurgitation ≥ 2 Heart failure re-admission 30-day mortality All-Cause mortality
Surgical AVR 17.8 (8.9-23.7) 47.6% 3 (1.4-4.5) 14.3% 4.8% 9.5% 9.5% 47.7%
TAVR 7.4 (3.2-11.8) 14.8% 1 (0.8-1.3) 7.5% 14.8% 14.8% 11.2% 51.8%
P value 0.01 0.01 <0.001 0.6 0.08 0.4 0.6 0.7
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PII: DOI: Reference:
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S1043-0679(16)30102-2 http://dx.doi.org/10.1053/j.semtcvs.2016.08.013 YSTCS896
To appear in: Seminars in Thoracic and Cardiovascular Surgery Accepted date: 31 August 2016 Cite this article as: Amgad Mentias, Nadeen N Faza, Mohammad Q. Raza, Ali Malik, Jasneet Devgun, L. Leonardo Rodriguez, Stephanie Mick, Jose L. Navia, Eric E. Roselli, Paul Schoenhagen, Lars G. Svensson, E Murat Tuzcu, Amar Krishnaswamy and Samir R. Kapadia, Management of Symptomatic Severe Aortic Stenosis in Patient with very Severe Chronic Obstructive Pulmonary D i s e a s e , Seminars in Thoracic and Cardiovascular Surgery, http://dx.doi.org/10.1053/j.semtcvs.2016.08.013 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
-Original researchManagement of Symptomatic Severe Aortic Stenosis in Patient with very Severe Chronic Obstructive Pulmonary Disease Amgad Mentias*, Nadeen N Faza *, Mohammad Q. Raza, Ali Malik, Jasneet Devgun, L. Leonardo Rodriguez, Stephanie Mick, Jose L. Navia, Eric E. Roselli, Paul Schoenhagen, Lars G. Svensson, E Murat Tuzcu, Amar Krishnaswamy and Samir R. Kapadia From the Heart and Vascular Institute, Cleveland Clinic, Ohio, USA. * Co-first authors. Both authors contributed equally to the work
Word Count: 4100 Funding: no funding was provided for this work. Disclosure: Dr. Eric Roselli: CONSULTANT FEES/HONORARIA - Bolton, Cook, Edwards Lifesciences, Gore, MEDTRONIC, Sorin, St Jude, Terumo. Remaining of authors has nothing to disclose.
Corresponding Author Samir R Kapadia, MD Professor of Medicine Director, Sones Cardiac Catheterization Laboratories Department of Cardiovascular Medicine, J2-3 Heart and Vascular Institute Cleveland Clinic 9500 Euclid Avenue Cleveland, OH 44195 Tel. 216-444-6735 Fax. 216-445-6176 Email: [email protected]
1
Abstract Background: Transcatheter Aortic Valve Replacement (TAVR) is a viable option for patients with severe Chronic Obstructive Pulmonary Disease (COPD) who are deemed inoperable or high risk for surgery. We sought to determine outcomes of patients with severe aortic stenosis (AS) and severe COPD referred for AVR. Methods: 131 patients with Severe AS and severe COPD (Gold criteria) were evaluated at our center between 2008 -2013 and were divided retrospectively into 4 groups: 1- medical management, 2- balloon aortic valvuloplasty, 3- surgical aortic valve replacement and 4- TAVR. Baseline, clinical, and echo data were recorded. Primary outcome was cardiovascular death. Results: From the study cohort 54(41.2%), 29(22.1%), 21 (16.0%), and 27 (20.6%) were included in groups 1-4 respectively. Age was 74.9±8.8, 76.2 ± 8.8, 78.8 ± 7.4 and 82.8 ± 6.8 years respectively (P <0.01). There was no significant difference between groups in hypertension, diabetes, aortic valve area or gradients, forced expiratory volume in first second, right ventricular systolic pressure, ejection fraction, and STS score. At 3±1.5 years, death occurred in 87%, 97%, 47.7% and 51.8% of patients respectively. Heart failure (HF) readmissions occurred in 43%, 42%, 9.6% and 14.8% respectively. When SAVR and TAVR groups were compared, there was no significant difference in survival (P=0.719) or HF readmissions (P=0.19). Conclusion: In severe/very severe COPD and Severe AS patients, replacing the severely stenotic aortic valve either by Surgical AVR or TAVR improves survival and reduces re-hospitalization compared to medical therapy or BAV. Keywords: Aortic valve stenosis, COPD, TAVR, Surgical aortic valve replacement.
2
List of Abbreviations: AS: Aortic stenosis AV: Aortic valve AVA: Aortic valve area AVR: Aortic valve replacement BAV: Balloon aortic valvuloplasty CAD: Coronary artery disease COPD: Chronic pulmonary obstructive disease DI: Dimensionless index EF: Ejection fraction FEV1: Forced expiratory volume in first second FVC: Forced vital capacity TAVR: Transcatheter aortic valve replacement MPG: Mean pressure gradient NYHA: New York Heart association PFT: Pulmonary function testing PPG: Peak pressure gradient RVSP: Right ventricular systolic pressure STS: The Society of Thoracic Surgeons TEE: Transesophageal echocardiography
3
Perspective: COPD increases mortality of aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Here, we compare outcomes in symptomatic severe AS patients with very severe COPD referred for surgical AVR versus TAVR. After follow up of 3 years, there was no difference in short and long-term mortality between both groups. On multivariate analysis, TAVR and surgical AVR both improved survival.
Central message: In severe COPD and AS, replacing the AV either by surgical AVR or TAVR improves survival and reduces re-hospitalization equally.
4
Introduction: Aortic stenosis (AS) is the most common valvular disease among the elderly population in the United States. In patients older than 65 years, the prevalence of symptomatic aortic stenosis is 4%1, and the prevalence is expected to grow as average life expectancy increases. Given its dismal natural course, once aortic stenosis is symptomatic the only effective treatment is aortic valve replacement2. The introduction of transcatheter aortic valve replacement (TAVR) has revolutionized the management of patients with AS, and is considered a viable option in high-risk and inoperable patients3,4. Medical management does not provide a mortality benefit in the management of symptomatic severe AS, and is used primarily to palliate patients who do not qualify for TAVR or Surgical AVR5. Lastly, percutaneous balloon aortic valvuloplasty (BAV) may be used as a palliative strategy, to better discern the contribution of aortic valve disease to functional decline in patients with competing comorbidities, or as a bridging measure for patients temporarily unable to undergo definitive therapy with Surgical AVR or TAVR6–9.Patients with AS are usually elderly and present with multiple major comorbidities. Chronic obstructive pulmonary disease (COPD) is the third leading cause of morality in the United States, its incidence increases with age10, and accordingly is diagnosed in up to 20% of patients presenting for Surgical AVR and 20-40% of patients presenting for TAVR.4,11,12 The Presence of COPD in patients undergoing Surgical AVR is significantly associated with a higher incidence of postoperative pneumonia, in addition to worse in-hospital and long-term mortality13–15. In the TAVR population, COPD is an independent predictor of in-hospital and long-term mortality16–18. Previous reports have studied outcomes of COPD patients undergoing TAVR and COPD patients
5
undergoing Surgical AVR
13,19
, but none of the previous studies have discussed approach with
different treatment strategies in this high risk population. The aim of our study was to determine outcomes in high-risk, symptomatic AS patients with severe/very severe COPD referred for multispecialty evaluation by a high risk AVR team and who ultimately were decided to undergo TAVR, Surgical AVR, BAV, or continued medical therapy.
Methods: As a part of a retrospective cohort study, we studied 131 patients who presented to our institution between March 2008 to September 2013 for high risk AVR evaluation with severe symptomatic aortic stenosis and severe or very severe chronic obstructive pulmonary disease (COPD) as classified by Gold criteria (Table 1). All patients were assessed by a high risk AVR team to determine eligibility for aortic valve replacement. Inclusion criteria in addition to diagnosis of COPD as above were: severe (AS) as defined by aortic valve area ≤ 0.8 cm2, mean pressure gradient ≥ 40 mmHg, or peak velocity across aortic valve ≥ 4 m/sec. All patients had symptomatic AS with NYHA class II or higher. Exclusion criteria were as follows: bicuspid aortic valve, history of aortic valve surgery, severe left ventricular dysfunction with EF ≤ 15%, history of myocardial infarction or stroke in the previous 6 months, severe mitral or aortic regurgitation. Baseline demographic characteristics, clinical status, and echocardiographic parameters were recorded in the first encounter. The Society of Thoracic Surgeons predicted risk of mortality score (STS) was calculated for all patients using the STS Adult Cardiac Surgery Risk Calculator. After evaluation by the high risk AVR team, patients underwent 1) Medical management 2) BAV 3) Surgical AVR or 4) TAVR.
6
All procedures and data collection were approved and monitored by the Cleveland Clinic Institutional Review Board (IRB) with waiver of individual informed consent. Echocardiography: A comprehensive Doppler echocardiographic evaluation was performed at the time of initial presentation according to the American Society of Echocardiography guidelines using commercially available instruments (Philips Medical Systems, NA, Bothell, WA; General Electric Medical Systems, Milwaukee, WI; and Siemens Medical Solutions USA, Inc, Malvern,PA). Left ventricular ejection fraction (EF), LV end systolic and end-diastolic volumes, left atrial dimensions, left ventricular diastolic function, left ventricular wall thickness and right ventricular systolic pressures (RVSP) were recorded. Aortic stenosis severity was assessed by calculating mean and peak pressure gradients according to modified Bernoulli equation, aortic valve area (AVA) by continuity equation, and dimensionless index (DI) using standard guidelines 20. Transcatheter aortic valve replacement: Patients who were determined as inoperable or at high-risk for surgical complications by the high risk AVR team underwent TAVR. The default approach to TAVR in patients with adequate iliofemoral access was transfemoral (TF); those patients for whom TF access was not possible on the basis of CT-analysis underwent alternative access (transapical or transaortic). All TAVR procedures were performed in hybrid operating rooms under general anesthesia and with guidance of transesophageal echocardiography (TEE). The Edwards SAPIEN valve series (9500 TFX and SAPIEN XT; Edwards Lifesciences, Irvine, CA) was used in all patients who underwent TAVR.
7
Balloon aortic valvuloplasty (BAV) Patients who were deemed inoperable or high-risk and did not undergo TAVR due to peripheral arterial disease, annulus size, unclear contribution of AS to functional decline due to comorbid conditions, or patient desire underwent BAV. This was performed via the standard retrograde approach using Z-med II balloons (B. Braun Medical Inc, Bethlehem, PA) sized according to left-ventricular outflow tract dimension and hemodynamic response. COPD assessment Pulmonary function testing was performed in our institution’s pulmonary function lab. All testing results were reviewed by an attending pulmonologist. COPD severity was defined by Gold Criteria (Table 1), and only patients with severe or very severe COPD [Forced expiratory volume in 1st second/Forced vital capacity (FEV1/FVC) ≤ 0.70 and FEV1 ≤ 50% predicted value] were included. Data pertaining to long-term oral corticosteroid therapy and home oxygen use was recorded. Follow up and outcomes: Patients were followed for a median of 3.0±1.5 years. Length of hospital stay and postoperative complications including prolonged intubation, re-intubation, stroke/transient ischemic attack and major bleeding requiring blood transfusion within the first 30 days were recorded for patients undergoing TAVR, Surgical AVR, BAV, and medical management. The primary outcome was all-cause mortality and secondary outcomes included immediate post-intervention respiratory complications such as prolonged intubation (defined as intubation for more than 24 hours); hospital readmission for COPD or heart failure, pneumonia, or respiratory failure; and new-onset home oxygen use.
8
Statistical analysis Continuous variables are expressed as mean ± standard deviation (SD), or median and inter-quartiles for skewed distributions, and compared using the Student t-test or ANOVA (for normally distributed variables) or the Wilcoxon test (for non‐normally distributed variables). Categorical data is expressed as a percentage and compared using Fisher exact or Chi-Square test. To assess outcomes, Cox proportional hazards analysis was performed to assess independent predictors of outcome (using a P-value cutoff of < 0.05 for statistical significance). Hazard ratios (HRs) with 95% confidence intervals were calculated and reported. Cumulative proportion of events as a function over time was obtained by the Kaplan‐Meier method to do the survival analysis. Statistical analysis was performed using JMP pro version 10.0.
Results: Baseline characteristics of the patients in each group are shown in table 2. Baseline echocardiography and pulmonary functions testing characteristics for patients in the four groups are shown in table 3. The mean age for the TAVR group was significantly greater than the three remaining groups (p = 0.0007). There were no significant differences between the four groups with respect to comorbid conditions, severity of AS, severity of COPD by PFT, or STS score at baseline. Five patients (18.5%) underwent TAVR through the transapical approach and the remaining underwent TF-TAVR. After follow up of 3 ± 1.5 years, the primary outcome of cardiovascular death occurred in 87%, 97%, 47.7% and 51.8% of patients in the four groups, respectively (p < 0.0001). The secondary outcomes of heart failure, respiratory failure, and COPD exacerbation 30 days readmissions occurred in 43%, 42%, 9.6% and 14.8% of patients, respectively (p = 0.016). 9
When comparing group 3 (Surgical AVR) and 4 (TAVR) only, the TAVR group was older (P=0.005), but there was no significant difference in sex (p = 0.3), smoking (p = 0.7), hyperlipidemia (p = 0.6), renal impairment (p = 0.6), hypertension (p = 0.2), history of stroke (p = 0.1), Coronary artery disease (p = 0.3), New York Heart Association (NYHA) class (p = 0.3), need for home oxygen (p = 0.7), STS score (p = 0.8), baseline left ventricular EF (p = 0.5), mean AV PG (p = 0.8), AVA (p = 0.3), RVSP (p = 0.2), FEV1% (p = 0.2) or FEV1/FVC (p = 0.6). The median length of hospital stay post-intervention was significantly longer for the surgical group (17.8 days, IQs 8.9-23.7 days) compared to the TAVR group (7.4 days, IQs 3.211.8 days) (p = 0.01). Prolonged intubation (> 24 hours) occurred in 47.6% and 14.8% of the SAVR and TAVR groups, respectively (p = 0.01). Tracheostomy was required in three (14.3%) and two (7.5%) patients in the Surgical AVR and TAVR groups, respectively (p = 0.6). Thirtyday mortality occurred in two (9.5%) patients in the surgical group and three (11.2%) patients in the TAVR group (p = 0.6). When the two patients who underwent BAV then TAVR were included in the TAVR group for analysis, there was still no difference in 30-day mortality between the two groups (9.5% vs. 9%, p=0.9) Follow up was completed in majority of the patients (98.5% overall in the study population, 96.3% in the TAVR group, and 95.2% in the surgical AVR group). EF, RVSP and functional status was assessed and reported from the last available follow up. Patients who underwent Surgical AVR had significant improvement in RVSP from 47 mmHg at baseline to 39 mmHg (p=0.01) in follow up, while RVSP did not show significant change in TAVR group. There was no significant change in EF before and after procedure in both groups (Figure 2). Patients in both groups showed significant improvement in functional class after the procedure, p<0.001. There was no difference in degree of improvement between TAVR and SAVR. P=NS. Data regarding 10
home oxygen use after the procedure was lacking for majority of the study sample, so it was not reported nor included in the analysis. Aortic regurgitation grade ≥ 2 at follow up was found in one (4.8%) and four (14.8%) patients in the Surgical AVR and TAVR groups, respectively. Post-procedural stroke occurred in one patient from each group, heart failure and COPD admissions in follow-up occurred in two (9.5%) and four patients (14.8%) in the Surgical AVR and TAVR groups (p=0.1), respectively. The primary outcome of all-cause mortality occurred in 47.7 and 51.8% (p = 0.7) of the patients in each group, respectively. When the two patients who crossed from BAV to TAVR arm were included in the final analysis, there was still no difference in mortality between both groups (47.7% vs 48.3%, p=0.9). On multivariable analysis, after adjusting for age and other predictors of worse outcomes, Surgical AVR or TAVR procedure both improved survival significantly (p = 0.12; OR 3.79, 95% CI: 0.70-20.49). Apart from age and gender, all other variables with p-value for difference between the two groups < 0.2 were included in the regression model for multivariable analysis. The Kaplan‐Meier curve showing long‐term outcomes in the four groups is shown in figure 3. Discussion Our study demonstrates that TAVR is similar to surgical AVR with respect to intermediate-term survival in patients with severe symptomatic AS and severe or very severe COPD. We also demonstrate in our analysis that TAVR in this population is associated with shorter hospital stay and less postoperative respiratory complications (including need for prolonged intubation) with similar rates of hospital readmission. COPD is a major limiting factor in patient selection for surgical intervention; this explains the higher prevalence of COPD in patients undergoing TAVR versus Surgical AVR in our group and other series’ 4,11,12. 11
The importance of chronic lung disease (CLD) in patients undergoing TAVR has been demonstrated by other investigators. Dvir and colleagues evaluated the impact of CLD on the outcomes of TAVR in 2500 patients. CLD was associated with higher mortality after one year compared to patients without CLD (23.4% vs. 19.6%, p = 0.02). In the same study, it was demonstrated that in patients with CLD and severe AS, TAVR and SAVR had comparable outcomes and is better than standard medical therapy. However, in contrast to our study, they did not specifically evaluate patients with COPD as opposed to other lung diseases.21 Mok and colleagues19 evaluated the outcomes of TAVR in COPD patients, though only 29.5% of their study population had COPD. In contrast, our entire study population included patients with significant COPD. More importantly, our study population had more severe and advanced COPD with a mean FEV1 of 37.8± 9.9% in comparison to an FEV1 of 60 ± 21% in the afore-mentioned study. This may partially explain the numerically worse survival in our group in comparison to that in the study by Mok and colleagues (48.2 vs 70.6%). In the analysis by Gunter and colleagues, COPD was not found to be significant predictor of in-hospital mortality, but was shown to be a strong incremental predictor of long-term mortality after Surgical AVR13. Three-year survival in severe COPD patients after SAVR was reported to be 63.5% compared to 52.2% in our study. They also demonstrated that COPD was a predictor of postoperative pneumonia, but failed to predict postoperative prolonged ventilation. Similarly, Spoon and colleagues
22
studied 41 patients with severe/very severe COPD who
underwent surgical AVR. 30-day mortality was reported as 4.9% (2 patients) compared with 9.5% (2 patients) in our study. Five-year survival for this group in that study was 52% compared to the 52% 3-year survival in our study.
12
Our study reveals that COPD patients undergoing Surgical AVR had a significantly higher incidence of prolonged intubation than those who underwent TAVR. This finding is consistent with a study by Thourani and colleagues23 who reported that preoperative severe COPD was only second to renal failure as an organ-specific poor prognostic factor in terms of survival after Surgical AVR. To our knowledge, this is the first study to compare outcomes of surgical AVR to TAVR in a single center in severe/very severe COPD patients. As such, we believe it contributes to the body of literature discussed above regarding patients with lung disease undergoing an AVR procedure. As the patient population referred for TAVR continues to expand, it is important to understand how comorbid conditions such as COPD should be considered in patient selection with respect to post-procedural outcomes including pulmonary complications. In this regard, it appears that patients with significant COPD fare better with TAVR than with Surgical AVR. As we move toward performing more TF-TAVR procedures without endotracheal intubation, we hypothesize that this separation in pulmonary outcomes would only increase and would be an important area for further investigation 24. Study limitations: Our study included a relatively small number of patients in each group which makes it underpowered. This is partly due to the fact that our inclusion criteria were strict to patients with severe/very severe COPD. Another limitation stems from the fact that this is a retrospective, single center study which might pose a selection bias and findings from this study might not be generalizable to other surgical centers. In addition, it has been reported that pulmonary function tests might overestimate COPD severity in patients with concomitant aortic stenosis patients25. Unfortunately, post-intervention pulmonary function testing were not available for comparison to 13
baseline pulmonary function testing to better evaluate the effect of aortic valve intervention on patients’ respiratory status. Our study is the first to compare outcomes of different management modalities in patients with severe aortic stenosis and severe COPD. Additional prospective studies are needed to better evaluate the effect of these management modalities, especially with the increasing use of TAVR as a viable, similar and less invasive treatment modality for severe aortic stenosis.
Conclusion: Transcatheter aortic valve replacement is similar to surgical aortic valve replacement for patients with severe aortic stenosis and severe/very severe COPD regarding long term survival, and offers shorter hospital stay with less postoperative respiratory complications.
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Rodés-Cabau J, Webb JG, Cheung A, et al. Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: acute and late outcomes of the multicenter Canadian experience. J Am Coll Cardiol. 2010;55(11):1080-1090. doi:10.1016/j.jacc.2009.12.014.
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Mok M, Nombela-Franco L, Dumont E, et al. 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(10):1072-1084. doi:10.1016/j.jcin.2013.06.008.
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Magee MJ, Herbert MA, Roper KL, et al. Pulmonary function tests overestimate chronic pulmonary disease in patients with severe aortic stenosis. Ann Thorac Surg. 2013;96(4):1329-1335. doi:10.1016/j.athoracsur.2013.04.123.
Figure 1: Flow chart of study population enrollment. Figure 2: Panel A: Incidence of postoperative complications between Surgical AVR and TAVR groups. CHF: congestive heart failure, COPD: chronic obstructive pulmonary disease, Panel B: Change in functional status at follow up. NYHA: New York Heart Association. Patients in both groups showed significant improvement in functional class after the procedure, p<0.001. Figure 3: Kaplan‐Meier curve showing survival in severe AS and very severe COPD managed by TAVR, Surgical AVR, BAV and medical therapy (p=<00.1 between all groups) (p=NS between TAVR and Surgical AVR)
17
Table 1 Gold's criteria for COPD severity. FEV1 forced expiratory volume in first second, FEV1/FVC forced expiratory volume in first second/forced vital capacity. Stage I Stage II Stage III Stage IV
Mild COPD Moderate COPD Severe COPD Very Severe COPD
FEV1/FVC<0.70 FEV1/FVC<0.70 FEV1/FVC<0.70 FEV1/FVC<0.70
FEV1≥ 80% normal FEV1 50-79% normal FEV1 30-49% normal FEV1 <30% normal
Table 2 Baseline characteristics for patients in the four groups. PVD peripheral vascular disease, CABG coronary artery bypass grafting. PCI: percutaneous coronary intervention. NYHA: New York Heart Association. STS Society of Thoracic Surgeons. BAV: balloon aortic valvulopasty. Variable Number Age (year) Sex (males) BMI (kg/m2) Smoking Diabetes mellitus Hyperlipidemia Renal impairment Hypertension History of stroke Pulmonary hypertension PVD Home oxygen History of CABG Prior PCI NYHA II NYHA III NYHA IV STS score
Medical 54 74.9±8.8, 46% 28.3±9.1 79.6% 46.3% 81.5% 29.6% 79.6% 11.1% 33.3% 46.3% 50% 40% 33% 3.7% 77.8% 16.7% 10.9±7.1
BAV 29 78.8 ± 7.4 44.8% 27.7±9.3 69%, 38% 65.5% 20.7% 75.9% 0% 34.5% 10.3% 51.7% 20.7% 24.1% 6.9% 65.5% 27.6% 10.3±6.7
Surgical AVR 21 76.2 ± 8.8 66.7% 28.2±9.4 85.7% 38.1% 81% 38.1% 76.2% 14.3% 47.6% 52.4% 33.3% 42.9% 28.6% 9.5% 52.4% 38.1% 11.4±5.9
TAVR 27 82.8 ± 6.8 81.5% 26.2±5.6 77.8% 37% 88.9% 37% 92.6% 37% 48.2% 33.3% 25.9% 44.4% 25.9% 11.1% 70.4% 18.5% 11.2±4.8
P value 0.0007* 0.008* 0.7791 0.54 0.81 0.17 0.49 0.29 0.004* 0.46 0.002* 0.1 0.23 0.87
0.93
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Table 3 Baseline echocardiography and pulmonary functions testing for patients in the four groups. EF Ejection fraction. PPG peak pressure gradient. MPG mean pressure gradient. AVA aortic valve area. RVSP right ventricular systolic pressure. Variable EF (%) PPG (mmHg) MPG (mmHg) AVA (cm2) RVSP (mmHg) FEV1/FVC FEV1% FEV1 FVC
Medical 45.7±16.4 68±27.6 40.1±17.7 0.65±0.2 52±19.9 50.7±12.2 36.6±10.7 0.85±0.27 0.5±0.12
BAV 44.5±17.1 82.3±30.9 49.6±18.9 0.61±0.2 46.6±12.7 49.4±12.1 37.4±10.6 0.81±0.26 0.49±1.2
Surgical AVR 45±16.5 83.5±28.1 47.9±19.5 0.61±0.2 46.6±12.7 49.4±12.1 38±7.1 1.04±0.29 0.47±0.12
TAVR 48.7±13.5 76.2±27.3 44.8±16.3 0.64±0.1 42.7±13 49±12.7 40.6±8.9 1.05±0.28 0.5±0.13
P value 0.76 0.087 0.11 0.71 0.18 0.74 0.39 0.05 0.4
Table 4: Comparison of outcomes after Surgical AVR versus TAVR in patients with severe/very severe COPD Outcome Length of hospital stay: Median (IQs) Prolonged intubation >24 hours Median intubation time (IQs) Tracheostomy Aortic regurgitation ≥ 2 Heart failure re-admission 30-day mortality All-Cause mortality
Surgical AVR 17.8 (8.9-23.7) 47.6% 3 (1.4-4.5) 14.3% 4.8% 9.5% 9.5% 47.7%
TAVR 7.4 (3.2-11.8) 14.8% 1 (0.8-1.3) 7.5% 14.8% 14.8% 11.2% 51.8%
P value 0.01 0.01 <0.001 0.6 0.08 0.4 0.6 0.7
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