Trans-apical Aortic Valve Replacement in Patients with History of Coronary Artery Bypass Grafting: An Analysis of the National Inpatient Sample Database S. Chiu Wong MD Professor of Medicine Weill Cornell Medicine Director, Cardiac Cath Labs New York Presbyterian Hospital –Cornell Campus CRT 2017 February 20th, 3:47 PM – 3:55 PM Omni Sheraton Washington DC

Impact of Previous CABG on Transapical TAVR Disclosure S. Chiu Wong MD: Edwards Lifesciences: Institutional Research Grant

Impact of Previous CABG on Transapical TAVR Background Following the initial FDA approval of TAVR for extreme risk /no option symptomatic AS pts, TAVR has expanded rapidly into both high and intermediate risk cohorts as an alternative to surgical AVR. Transapical (TA)-TAVR was the 1st non-transfemoral access tried and remains the most frequently applied in the US. As of Dec. 31st, 2014, the TVT registry summarized the US experience on 26,414 TAVR procedures at 348 US centers; 32.5% had prior cardiac surgery and 23.2% of valves were implanted with mini-thoracotomy via TA access. Peri-procedural clinical outcomes in pts with prior history of CABG undergoing TA-TAVR are currently not well characterized.

Impact of Previous CABG on Transapical TAVR Objectives and Endpoint Definitions: Using the 2011-2013 Nationwide Inpatient Sample [NIS] database, we sought to compare the clinical characteristics and in-hospital procedural outcomes following TA-TAVR in pts with & without history of CABG. The primary endpoint was a composite of in-hospital major complications including all-cause death, stroke, AMI and emergent conversion to open heart surgery. The secondary endpoint included incidence of acute respiratory failure, pneumothorax, vascular complication, bleeding requiring transfusion, acute kidney injury requiring dialysis, pacemaker implantation, length of stay, and discharge to home.

Impact of Previous CABG on Transapical TAVR Methods (1) We identified pts who underwent TA-TAVR in the NIS database using ICD-9-CM procedure codes. Among these pts, those with no prior history of any cardiac surgery [De novo] and those with prior CABG [Re-Op] were included. Pts < 65 years old or missing mortality data were excluded. 1:1 propensity score matching was applied to adjust for differences in pt and procedural factors between the De Novo and Re-Op cohorts. Matched cohorts were compared using paired t test, McNamer test or conditional logistic regression. After matching, standardized differences for all measured covariates between matched cohorts were < 10 % suggesting successful match.

Impact of Previous CABG on Transapical TAVR Methods (2) To further adjust for potential selection bias for De Novo versus Re-Op cohorts, additional multivariate logistic regression analyses were performed to compare each outcome between the 2 cohorts following TA-TAVR with propensity score incorporated as an additional variable in the multivariate model. Model fit for each regression model was assessed using C-statistic and Hosmer-Lemeshow χ2 statistic.

Impact of Previous CABG on Transapical TAVR Results (1) Consort Flow Chart During the study period, the NIS contained deidentified information on 22,440,121 discharges. Of the 4,266 TAVR patients who were at least 65 years of age with in-hospital survival data, 1,003 (23.7%) underwent TA-TAVRs (737 de Novo and 235 Re-Op, Figure 1).

Impact of Previous CABG on Transapical TAVR Results(1) Patient Characteristics After Matching Cohort De Novo Re-Op P value Number of patients (%) N=207 - Age (mean ± SD) 81.5 ± 6.9 81.0 ± 6.2 0.50 Women 78 (37.7%) 77 (37.2%) 0.91 Race White Nonwhite   174 (84.1%) 33 (15.9%) 175 (84.5%) 32 (15.5%) 0.90 Hypertension 182 (87.9%) 183(88.4%) 0.88 Diabetes Mellitus 99 (47.8%) 1 Dyslipidemia 158 (76.3%) 162 (78.3%) 0.60 Chronic Kidney Disease 97 (46.9%) 91 (44.0%) 0.58 History of Stroke 21 (10.1%) 22 (10.6%) Chronic pulmonary disease 60 (29.0%) 61 (29.5%) 0.92 Pulmonary Hypertension 37 (17.9%) 35 (16.9%) 0.79 Peripheral Vascular Disease 81 (39.1%) After propensity matching (Table 2), the clinical characteristics were well balanced

Impact of Previous CABG on Transapical TAVR Results(2) Patient Characteristics After Matching  Cohort De Novo Re-Op P value Number of patients (%) N=207 - Congestive Heart Failure 145 (70.1%) 144 (69.6%) 0.91 Coronary Artery Disease 207 (100%) Malignancy 27 (13.0%) 29 (14.0%) 0.76 Coagulopathy 55 (26.6%) 51 (24.6%) 0.63 Anemia 59 (28.5%) 52 (25.1%) 0.47 Obesity 23 (11.1%) 26 (12.6%) 0.64 Previous PCI 44 (21.3%) 1 Charlson/Deyo comorbidity index, (mean ± SD) 3.0 ± 1.7 3.0 ± 1.8 0.77 Primary payer: Medicare/Medicaid  195 (94.2%) 193 (93.2%) 0.57 Hospital bed size Small Medium Large   13 (6.3%) 40 (19.3%) 154 (74.4%) 43 (20.8%) 151 (73.0%) 0.61

Impact of Previous CABG on Transapical TAVR Results (3): In Hospital Clinical Outcomes In-Hospital Outcomes Total (n=414) De Novo (n=207) Re-Op OR*  (95% CI) P value Adjusted OR† Primary Endpoints  24 (5.8%)  15 (7.3%)  NA  0.50 (0.15-1.44) 0.24  0.49 (0.20-1.17)  0.11 All-cause Mortality 12 (2.9%) NA 0.25 (0.03-1.25) 0.29 (0.08-1.07) 0.06 Stroke 1.50 (0.17-17.96) 1 1.04 (0.23-4.82) 0.96   Myocardial Infarction 0.67 (0.06-5.82) 0.54 (0.09-3.35) 0.51      Conversion to cardiac surgery 0.39 (0.07-2.33) 0.30 Secondary Safety Endpoints 150 (36.2%)  78 (37.7%)   72 (34.8%)  0.88 (0.58-1.32)  0.53 1.00 (0.70-1.43)      Acute respiratory failure 27 (6.5%) 17 (8.2%) 0.59 (0.27-1.29) 0.18 0.57 (0.28-1.17) 0.13      Pneumothorax 1.00 (0.13-7.47) 0.56 (0.17-1.85) 0.34      Vascular Complication 20 (4.8%) 11 (5.3%) 1.22 (0.46-3.34) 0.82 1.13 (0.46-2.77) 0.79      Blood Transfusion 84 (20.3%) 42 (20.3%) 1.00 (0.60-1.67) 1.35 (0.85-2.15) 0.20      Acute Kidney Injury requiring hemodialysis 1.00 (0.23-4.35) 1.01 (0.35-2.86) 0.99      Permanent Pacemaker Implant 33 (8.0%) 18 (8.7%) 15 (7.3%) 0.82 (0.41-1.67) 0.59 0.87 (0.48-1.59) 0.65 Length of stay, mean±SD (median) 9.1±6.0 (7.0) 9.6±7.1 (7.0) 8.6±4.7 (7.0) - 0.37 Length of stay ≥ 8 days‡ 193 (46.6%) 92 (44.4%) 101 (48.8%) 1.18 (0.81-1.72) 0.39 1.04 (0.72-1.50) Discharge to home 258 (64.2) 114 (57.6) 144 (70.6) 1.84 (1.19-2.85) 0.01 2.16 (1.46-3.21) 0.0001 There was no significant difference in the in-hospital primary endpoints; 7.3 % in the de Novo group and 4.4% in the Re-Op group (OR = 0.5 [0.15-1.44], P = 0.24) nor in each of its composites elements, including all-cause mortality, stroke, AMI, or conversion to surgery. Similarly, there was also no difference in the composite secondary endpoint (37.7% De Novo vs. 34.8% Re-Op, P = 0.53) with similar incidences of acute respiratory failure, pneumothorax, vascular complication, blood transfusion, acute kidney injury, permanent pacemaker implant, or in the length of stay. However, Re-Op patients were more likely to be discharged home following TA-TAVR than De novo patients (70.6% vs. 57.6%, OR = 1.84 [1.19 - 2.85], P = 0.01). Multivariate logistic regression analyses confirmed the clinical equipoise between the two cohorts with a strong trend towards a lower all-cause mortality and a significant higher likelihood to be discharged home in Re-op patients following the procedure. *†No prior cardiac surgery as reference. NA (not available) = National Inpatient Samples database user agreement prohibits reporting variables involved ≤ 10 patients. †Multivariate logistic regression model was based on a total sample of 972 patients (4,825 patients, weighted). For primary endpoints, all-cause mortality, stroke, myocardial infarction, conversion to open heart surgery, secondary safety endpoint, acute respiratory failure, pneumothorax, vascular complication, blood transfusion, acute kidney injury requiring hemodialysis, permanent pacemaker implant, length of stay ≥ 8 days and discharge to home, the C statistics of the receiver operator characteristic curves were 0.77, 0.76, 0.80, 0.89, 0.81, 0.71, 0.74, 0.67, 0.67, 0.72, 0.88, 0.69, 0.75 and 0.76, respectively with all P values of Hosmer-Lemeshow goodness of fit test > 0.05. No covariates were found to be collinear. ‡Median of 8 days was based on the entire study sample of 972 patients.

Impact of Previous CABG on Transapical TAVR Limitations (1) Events in the NIS database were self-reported, not adjudicated or audited and only 20% of the available data were sampled. No uniform definitions for complications such as VARC classification on bleeding or AKI or severity of stroke using Rankin score were available. Relevant procedural variables including procedural or intubation time & chest tube drainage volume were not collected. No detailed hemodynamic data, severity of post TAVR valvular regurgitation nor any out of hospital clinical outcomes data were available.

Impact of Previous CABG on Transapical TAVR Limitations (2) Although the matched cohorts had similar Charlson/Deyo comorbidity index, the STS score was not available. In addition, due to the observational nature of registry data, a lack of uniform discharge policy amongst participating hospitals, fragility assessment & other confounders makes speculation of reasons accounting for the significant difference in discharge to home between de Novo and Re-Op patients rather difficult. Charlson index[edit] The Charlson comorbidity index[4] predicts the one-year mortality for a patient who may have a range of comorbid conditions, such as heart disease, AIDS, or cancer (a total of 22 conditions). Each condition is assigned a score of 1, 2, 3, or 6, depending on the risk of dying associated with each one. Scores are summed to provide a total score to predict mortality. Many variations of the Charlson comorbidity index have been presented, including the Charlson/Deyo, Charlson/Romano, Charlson/Manitoba, and Charlson/D'Hoores comorbidity indices. Clinical conditions and associated scores are as follows: 1 each: Myocardial infarct, congestive heart failure, peripheral vascular disease, dementia, cerebrovascular disease, chronic lung disease, connective tissue disease, ulcer, chronic liver disease, diabetes. 2 each: Hemiplegia, moderate or severe kidney disease, diabetes with end organ damage, tumor, leukemia, lymphoma. 3 each: Moderate or severe liver disease. 6 each: Malignant tumor, metastasis, AIDS. For a physician, this score is helpful in deciding how aggressively to treat a condition.

Impact of Previous CABG on Transapical TAVR Conclusions In high or extremely risk symptomatic AS patients undergoing TA-TAVR for treatment of native AS in the 2011 to 2013 NIS database, there was no difference in the in-hospital clinical outcomes in De Novo compared to Re-Op patients. Re-Op patients were more likely to be discharged home compared to de Novo patients and trended towards a lower in-hospital mortality following TA-TAVR.

Thank You!!