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Prior and peri-operative revascularization does not affect survival in lung transplant patients
Journal Pre-proof Prior and peri-operative revascularization does not affect survival in lung transplant patients Jay Kanaparthi, BS, Mohammed A. Kashem, MD, PhD, Manish Suryapalam, Huaqing Zhao, PhD, Stacey Brann, MD, Eros Leotta, MD, Kenji Minakata, MD, Suresh Keshavamurthy, MD, Norihisa Shigemura, MD, Yoshiya Toyoda, MD, PhD PII:
S0003-4975(20)30229-0
DOI:
https://doi.org/10.1016/j.athoracsur.2020.01.016
Reference:
ATS 33502
To appear in:
The Annals of Thoracic Surgery
Received Date: 11 February 2019 Revised Date:
8 January 2020
Accepted Date: 9 January 2020
Please cite this article as: Kanaparthi J, Kashem MA, Suryapalam M, Zhao H, Brann S, Leotta E, Minakata K, Keshavamurthy S, Shigemura N, Toyoda Y, Prior and peri-operative revascularization does not affect survival in lung transplant patients, The Annals of Thoracic Surgery (2020), doi: https:// doi.org/10.1016/j.athoracsur.2020.01.016. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. 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. © 2020 by The Society of Thoracic Surgeons
Prior and peri-operative revascularization does not affect survival in lung transplant patients Reading Head: PCI, CABG, Concomitant CABG in Lung Tx
Jay Kanaparthi1 BS, Mohammed A Kashem MD2, PhD, Manish Suryapalam3, Huaqing Zhao2 PhD, Stacey Brann2 MD, Eros Leotta2 MD, Kenji Minakata2 MD, Suresh Keshavamurthy3 MD, Norihisa Shigemura2 MD, Yoshiya Toyoda2 MD, PhD
1
Lewis Katz School of Medicine at Temple University, 3500 N Broad Street, Philadelphia,
PA, 19140; 2Division of Cardiovascular Surgery, Temple University Medical Center, 3401 N Broad Street, Suite 301 Zone C, Philadelphia, PA, 19140; 3Temple University, 1801 N Broad St, Philadelphia, PA 19122; 4Division of Cardiothoracic Surgery, University of Kentucky, 740 S. Limestone, Lexington, KY 40536
Classifications: Coronary artery bypass grafts, CABG Coronary stents, PCI Revascularization Statistics, survival analysis Transplantation, lung Word Count: 4246
Corresponding Author: Yoshiya Toyoda MD, PhD 3401 N Broad Street, Suite 301 Zone C, Philadelphia, PA, 19140 [email protected]
1
Abstract Background: Coronary artery disease is common in lung transplant patients and has historically been viewed as a contraindication to the procedure. Although this mindset is changing, the effect of prior or peri-operative revascularization on lung transplant survival outcomes is not adequately established. Methods: We performed a single-center retrospective analysis of all single and double lung transplant patients from 2012-2018 (n=468). Patients were split into four groups: 1) patients that received a pre-operative PCI (n=34), 2) patients that received coronary artery bypass grafting prior to transplantation (n=25), 3) patients that received concomitant coronary artery bypass grafting during transplantation (n=29), and 4) patients that had lung transplantation with no need for revascularization (n=380). Groups were compared for demographics, surgical procedure, and survival outcomes. Results: The no revascularization group was statistically younger than the rest (p=0.001). The lung allocation score trended towards being higher in the concomitant coronary artery byspass (p=0.03). All groups were predominantly diagnosed with IPF. The proportion of patients with COPD was greatest in the group not requiring revascularization (p=0.001). Patients with previous coronary artery bypass grafting were more likely to receive a single lung transplant than a double (21 vs 4, P=0.054). Length of stay, post-transplant survival, and postoperative adverse events were similar amongst all groups. Conclusions: Results suggest preoperative or intraoperative revascularization does not negatively impact survival in lung transplant patients; lung recipients with coronary artery disease have comparable survival when adequately revascularized.
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Lung transplantation (LTx) is a crucial therapy for an array of end-stage lung diseases. To date, over 50,000 lung transplants have occurred, and the relative increase in lung transplants exceeds that of any other organ transplant over the last 10 years [1,2]. As operative techniques and peri-transplant care have developed over the last several decades, post-transplant outcomes have naturally increased. Thus, patients historically considered ineligible for LTx can now qualify to be lung recipients. Although survival rates are increasing, graft failure, infection, multiple organ failure, and cardiovascular disease remain significant causes of death. Cardiovascular causes of death lead to 11.6% of deaths within the first month of transplant and 7% of deaths beyond 10 years [1]. Coronary artery disease (CAD) historically was a contraindication to LTx, but recently was redefined as a relative contraindication [3]. Existing CAD is thought to pose a health risk for transplant patients because long-term immunosuppression can promote further atherosclerosis. Therapies for CAD in general populations include revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Several studies show that PCI and CABG show similar outcomes, but PCI is generally associated with increased need for repeat revascularization, and CABG shows better outcomes in multivessel disease and more complicated, non-linear atherosclerotic buildup [4,5,6] For potential lung transplant recipients with CAD, revascularization options include PCI or CABG prior to transplant or concomitant CABG during the transplantation. Transplant patients with less severe CAD may be deemed amenable to pre-transplant PCI. However, revascularization with PCI may not be a good option when the anatomy of the stenosis is not favorable for PCI, as seen in left main disease, bifurcating lesions, occluded lesions, etc. These cases may benefit from concomitant CABG because of the long-term benefit of left internal mammary artery-left anterior descending coronary artery
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bypass grafting and multi-vessel bypasses over PCI. Decisions regarding patient viability for revascularization and type of technique are left to the discretion of transplant centers as per the 2014 ISHLT Pulmonary Transplant consensus report [3]. Some studies suggest that concomitant CABG with LTx has demonstrated similar outcomes to LTx [7,8,9]. However, the long-term survival in these patients has still not been adequately established. In this study, we analyzed all lung transplant recipients at our institution over the past 6 years to compare survival outcomes of patients that have received a preoperative PCI, pre-operative CABG, concomitant CABG, or did not require revascularization.
Patients and Methods This study has been approved by the regulatory institutional review board of the Temple University Health System. We performed a single center review of all single and double lung transplant patients who underwent LTx at our center from February 2012 to August 2018. Patients were sorted into four groups: 1) patients that had received a preoperative PCI, 2) patients that had received coronary artery bypass grafting prior to transplantation, 3) patients that had received concomitant coronary artery bypass grafting during transplantation, and 4) patients that had lung transplantation with no need for revascularization. At our center, patients with severe coronary artery disease with no other major contraindications were accepted for either concomitant CABG or pre-operative PCI. We define significant CAD by a positive fractional flow reserve (FFR) less than 0.8 or or instantaneous wave-free ration (iFR) less than 0.9. Preoperative PCIs were performed by interventional cardiologists using balloon catheterization and drug-eluting stents. When patients were deemed anatomically not amenable to PCI, concomitant CABG was
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considered. Many of the CABGs performed prior to transplants were performed at other centers prior to the transplant referral at our center. Our strategy was to perform single lung transplantation in the chest contralateral to patent IMA graft.
Statistical Analysis Data were expressed as mean ± standard deviation or median where applicable for continuous variables and frequencies with percentages for categorical variables. The cohorts were compared for a number of parameters such as lung allocation score (LAS), length of stay (LOS), major adverse cardiac and cerebrovascular event (MACCE) rates, revascularization following transplant, incision type, grafts used, age, pump, and, most importantly, survival time. All scalar variables, which consisted of age, ischemic time, LOS, and LAS, were analyzed, pooled over strata by a Kruskal-Wallis one-way ANOVA test due to the non-normality. Ischemic time and LOS were additionally assessed pairwise over strata for significance. Only the No Revas cohort was nonnormal for ischemic time, so pairwise analysis was performed using Mann-Whitney UTests for pairs including the No Revas cohort and ANOVA with post-hoc Tukey’s HSD for pairs excluding the No Revas cohort. For LOS, all pairwise comparisons were assessed using Mann-Whitney U-Tests due to non-normality in all cohorts. Survival data were assessed by Kaplan-Meier curve and compared by Breslow, Tarone-Ware, and log-rank tests pooled over strata in order to assess significance at earlier, middle, and later points in the time course. Survival was confirmed in all patients since the closing of the study, and no patients were lost to follow-up. Hence, analysis of completeness of follow-up was not performed. Further analysis was performed pairwise over strata. Cox Regression was then performed using variables with statistically significantly different distributions across the four cohorts, which consisted of age, LAS, diagnosis, and
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gender. A p-value less than 0.05 was considered statistically significant. All the data were analyzed using SPSS 25.0 (IBM Corp., Aramonk, NY).
Results Of the patients analyzed, 34 required preoperative PCI, 25 received previous CABG, 29 required concomitant CABG, and 380 did not require revascularization (Table 1). There was a significant difference in recipient age between the groups (p=0.001), which was primarily driven by the distribution in age of the No Revas cohort, especially in comparison to the CABG-Pre cohort (p=0.006). Patients with no revascularization were the youngest, whereas patients with CABG prior to transplantation were the oldest. The cohorts showed no statistical difference in LOS, ischemic time, CPB time, or pump (Table 1). The most common diagnoses requiring lung transplantation at our center were idiopathic pulmonary fibrosis (IPF, 64%), followed by chronic obstructive pulmonary disease (COPD, 22%). There was significant difference in diagnosis between groups with the relative higher ratio of patients with COPD in the group not requiring revascularization (p=0.001). Other less common diagnoses included sarcoidosis, obliterative bronchiolitis, bronchiolitis obliterans with organizing pneumonia, bronchiectasis, alpha-1-antitrypsin deficiency, pulmonary hypertension, scleroderma, Sjogren's syndrome, and pulmonary fibrosis. The rates of single and double lung transplants were similar in all groups except in the group that had previously undergone CABG. This group was more likely to receive a single lung transplant over a double (21 vs 4, P=0.003) because of our strategy to avoid performing lung transplant in the chest ipsilateral to patent internal mammary grafts. This group was the primary contributor to our relatively low p value for single vs. double lung transplant (p=0.054), although it still did not reach statistical significance.
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In patients with concomitant CABG, the number of bypass grafts ranged from 1 to 3 (mean 1.6 ± 0.6). CABG was done using saphenous venous grafts and/or left internal mammary arteries (Table 2). The most common conduit utilized was LIMA-LAD whereas the most common venous graft was SVG-PDA (Table 2). 15 of the concomitant patients needed more than one graft (grafts=32: mean 2.1 median: 2). Median sternotomy (grafts=24: mean 1.8 median: 2), antero-axillary thoracotomy (grafts=12: mean 1.3 median: 1), and clamshell approach (grafts=7: mean 1.5 median: 1.5) were used while performing lung transplantation and CABG concomitantly (Table 3). Surgical exposure to the lung and coronary arteries was considered when determining surgical approach. Concomitant CABG with median sternotomies involved left internal mammary artery (LIMA) graft in all but one instance, whereas saphenous vein grafts were the exclusive conduits when a clamshell incision was used. The antero-axillary approach included both methods of grafting.
The mean times from revascularization to lung transplantation in the CABG-Pre and PCI-Pre cohort were 4.0±4.1 and 7.8±6.4 years respectively and the median times were 3 and 4.5 years respectively between revascularization and transplant, which showed a statistically significant difference (p=0.015). We routinely perform off pump lung transplantation. However, when patients are on ECMO preoperatively, we continue to use ECMO intraoperatively. When we need to initiate pump intraoperatively, we use either cardiopulmonary bypass or veno-arterial ECMO. In patients with concomitant CABG, we utilized cardiopulmonary bypass (n=12), veno-venous ECMO (n= 1), or veno-arterial ECMO (n= 3) intra-operatively for both concomitant and regular lung transplantation. However, all concomitant CABGs were performed on a beating heart without cardioplegic arrest.
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Assessment of the primary graft dysfunction (PGD) rate in the CABG-Con showed ten patients had a PGD Grade of 0, four had a PGD grade of 1, three had a PGD grade of 2, and twelve had a PGD grade of 3. Additionally, post-operative MACCE and revascularization rates are shown in Table 4. There was no significant difference between groups, which is promising but may be due to the small sample size of each group. Kaplan-Meier analysis was performed using Breslow (p=0.668), Tarone-Ware (p=0.429), and Log-Rank (p=0.186) tests pooled over strata in order to assess significance at earlier, middle, and later points in the time course. All three tests indicated that the difference between the survival rates of the four cohorts was statistically insignificant. Further analysis was performed pairwise over strata, but still revealed no significant difference in survival rate. A cox regression was then performed with variables determined to have a statistically significant difference in distribution between cohorts, which consisted of age, LAS, diagnosis, and gender. These produced p values of 0.751, 0.582, 0.611, and 0.119 respectively, as well as an overall p value of 0.593 for the regression. As indicated by the p-values, none of these variables were determined to have a statistically significant effect on lung transplant survival.
Comment The results of this study suggest that lung transplant patients with past coronary revascularization or concomitant revascularization demonstrate similar outcomes to other lung transplant patients. This supports the idea that patients with history of CAD or coronary revascularization procedures (PCI or CABG) can be considered for lung transplantations. Additionally, patients seeking lung transplantation with severe stenosis not amenable to PCI may pursue concomitant CABG and lung transplantation with no statistical change in survival.
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Our results suggest patients with coronary artery disease that received revascularization show similar rates of survival to those that do not require revascularization. This is in concordance with previous studies. Zanotti et al. compared lung transplant outcomes in 362 patients without CAD and 177 with moderate CAD and determined that moderate CAD did not increase peri-operative morbidity or decrease survival [10]. However, their analysis did not include patients with prior revascularization surgeries or patients with severe CAD (occlusion >70%), which are included in our study. Chaikriangkai et al. also found that preoperative coronary artery disease did not increase mortality risk but suggested that subsequent nonfatal cardiovascular events were increased, with a 12% annualized rate of post-transplant vascular events for patients with significant CAD vs 1% in patients with mild or no CAD [8]. Our study did not find an increase in acute cardiovascular events in this group. Koprivanac et al. performed a 1:1 matched analysis of 61 patients with CAD that had undergone revascularization with patients with mild to no CAD (<50% stenosis) and found no difference in post-transplant survival [11]. More recently, Mackey et al. did not find a statistically difference in survival probability in patients with CAD and patients without CAD (p=0.08) [9]. Additionally, they found that incidences of cardiac causes of death were rare in CAD patients receiving lung transplantation (2 of 56 deaths). Our paper corroborates these findings through survival and MACCE analysis. Concomitant CABG could not be studied in this analysis by Mackey et al., as none were performed during their study period. Support for revascularization with lung transplantation has been suggested by several papers [12,13]. Sherman et al. compared 27 lung recipients that had undergone PCI or concomitant CABG with 81 control recipients, and much like our paper, demonstrated similar survival and peri-operative adverse events in the two groups [7]. Parekh et al. found that in lung transplant with concomitant cardiac procedures,
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predominantly foramen ovale or atrial septal defect surgeries, similar 5-year survival was observed as compared to patients without these concomitant procedures [12]. In two more recent papers, Castleberry et al. and Biniwale et al. also examined concomitant cardiac surgery (CCS), with the former focusing more on PCI and CABG. Both found similar rates of survival as well as outcomes amongst CCS and non-CCS lung transplant groups. Castleberry et al. reported longer duration of mechanical ventilation and length of stay in patients with concomitant surgery [13]. Conversely, Biniwale et al. suggested CCS does not negatively impact peri-operative care [14]. These authors suggested better selection in patients as the reason for their better outcomes. Our results also demonstrated similar outcomes, but unlike Castleberry et al. we showed no statistical difference in length of stay. Furthermore, our concomitant CABG patients were older and had higher LAS compared to our patients with no revascularization, which indicates that our concomitant CABG group were potentially sicker and more at-risk patients. Despite these factors, our CABG-Con group had excellent outcomes with no incidents of CVA or other ischemic events and 100% survival in the first year. Castleberry et al. also warned of the risks of performing concomitant CABG in patients over the age of 65. Although our analysis did not perform statistical analysis stratified for age, 15 out of 28 of our concomitant CABG group exceeded the age of 65 (7 patients were >70 years of age) and we observed comparable survival in this cohort, suggesting strong outcomes can be achieved with excellent intraoperative management by an experienced team. McKellar et al. analyzed United Network for Organ Sharing (UNOS) data to suggest that lung transplantation in patients with prior CABG demonstrated better outcomes with single lung transplant over double lung transplant [15]. We did not directly compare SLT and DLT in our study, because very few DLTs were performed in our CABG-pre group. We were wary of potential hazards of entering the ipsilateral chest to
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the patent internal mammary artery graft, and therefore we more selectively performed SLTs contralateral to the patent graft in these patients. Additionally, McKellar et al. found statistically different survival between transplant recipients with prior CABG and recipients with no prior CABG at all time points (30 days: 94% vs 97%, 1 yr: 80% vs 89%, 5 yr: 66% vs 70%; p < 0.01). This conflicts with our study. McKellar et al. has much greater statistical power due to the size of the UNOS registry (14,499 No CABG patients, 292 CABG patients). The difference may also be due to advancements in the procedure as McKellar et al. used UNOS data from 2004 to 2013, whereas our data was from 2012 to 2018. Additionally, the strong outcomes could be due to factors related to our experienced team’s management of transplants complicated by CAD and careful prevention of causing peri-operative cardiac events. However, this study, like many of its type, is somewhat limited in its statistical power due to the relative infrequency of concomitant CABG with lung transplantation. While this study tracked yearly survival over six years, more thorough analysis of medical condition post-surgery is warranted. We address survival and MACCE rates as determinants of success but do not more thoroughly assess quality of life or nonMACCE complications after discharge. Additionally, this study carries the typical confounders of a single center design. Our outcomes have the risk of not being broadly applicable, as factors such as surgeon skill and team efficiency vary from site to site. The historic apprehension to performing lung transplants in CAD patients was partly due to overall scarcity of organ pools. This body of research serves to add patients to the potential recipient pool, but we do acknowledge that efforts must be made to increase the overall potential donor pool. Thus, it is imperative that actions are taken to increase both the rate of donation and usability of existing organs through technological advancement, such as ex vivo perfusion.
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Overall, our study supports the inclusion of CAD patients in the lung transplant recipient pool. Additionally, it corroborates the growing notion that concomitant CABG is a viable option in the context of lung transplantation by an expert team. We hope our strong outcomes help motivate further use of the concomitant CABG procedure as well as consideration of CAD patients for transplants.
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References: 1. Yusen RD, Edwards LB, Dipchand AI, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Lung and Heart– Lung Transplant Report—2016; Focus Theme: Primary Diagnostic Indications for Transplant. J Heart Lung Transplant. 2016;35(10):1170-1184. 2. Adegunsoye A, Strek ME, Garrity E, et al. Comprehensive Care of the Lung Transplant Patient. Chest. 2017;152:150-64. 3. Weill D, Benden C, Corris P, et al. A consensus document for the selection of lung transplant candidates: 2014- An update from the pulmonary transplantation council of the international society for heart and lung transplantation. J Heart Lung Transplant. 2015;34:1-15. 4. Putzu A, Gallo M, Martino EA, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention with drug-eluting stents for left main coronary artery disease: A meta-analysis of randomized trials. Int J Cardiol 2017;241:1428. 5. Lee CW, Ahn JM, Cavalcante R, et al. Coronary Artery Bypass Surgery Versus Drug-Eluting Stent Implantation for Left Main or Multivessel Coronary Artery Disease: A Meta-Analysis of Individual Patient Data. JACC Cardiovasc Interv. 2016;9:2481-9. 6. Spadaccio C, Benedetto U. Coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) in the treatment of multivessel coronary disease: quo vadis? —a review of the evidences on coronary artery disease. Ann Cardiothorac Surg 2018;7(4):506-515. 7. Sherman W, Rabkin DG, Ross D, et al. Lung transplantation and coronary artery disease. Ann Thorac Surg 2011;92:303-308.
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8. Chaikriangkrai K, Jyothula S, Jhun HY, et al. Impact of pre-operative coronary artery disease on cardiovascular events following lung transplantation. J Heart Lung Transplant. 2016;35(1):115. 9. Makey IA, Sui JW, Huynh C, et al. Lung transplant patients with coronary artery disease rarely die of cardiac causes. Clin Transplant. 2018;32:e13354. 10. Zanotti G, Hartwig MG, Castleberry AW, et al. Preoperative mild- to-moderate coronary artery disease does not affect long-term out- comes of lung transplantation. Transplantation. 2014;97(10):1079. 11. Koprivanac M, Budev MM, Yun JJ, et al. How important is coronary artery disease when considering lung transplant candidates? J Heart Lung Transplant. 2016;35(12):1453. 12. Parekh K, Meyers BF, Patterson GA et al. Outcome of lung transplantation for patients requiring concomitant cardiac surgery. J Thorac Cardiovasc Surg 2005; 130: 859-863. 13. Castleberry AW, Martin JT, Osho AA, Hartwig MG, Hashmi ZA, Zanotti G, et al. Coronary revascularization in lung transplant recipients with concomitant coronary artery disease. Am J Transplant. 2013;13:2978-88. 14. Biniwale R, Ross D, Iyengar A, Kwon OJ, et al. Lung transplantation and concomitant cardiac surgery: Is it justified? J Thorac Cardiovasc Surg. 2016;151(2): 560-67 15. McKellar SH, Bowen ME, Baird BC, et al. Lung transplantation following coronary artery bypass surgeryimproved outcome following single-lung transplant. J Heart Lung Transplant. 2016;35(11):1289-94
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Table 1. Demographics and Surgical Procedure Factor Patient Age (years) Gender M F LAS LOS (days) Ischemic Time CPB Time Diagnoses COPD IPF Othera Single vs Double SLT DLT HLTb Pump VV ECMO VA ECMO CPB Off
CABG- Con 66 ± 5
CABG-Pre 69 ± 5
PCI-Pre 67 ± 6
No Revas 63 ± 10
P value P=0.001
25 4 58 ±21 27.1±6.1 261.2±23.2
20 5 51 ±18 23.4±6.3 294.5±23.1
31 3 56 ±21 36.79±8.7 272.0±24.6
229 151 50 ±20 30.3±2.1 255.1±7.0
P=0.000 P=0.030 P=0.334 P=0.563
190.9±62.6
132.7±72.7
199.3±63.1
193.9±65.6
P=0.481
3 (10%) 24 (83%) 2 (7%)
2 (8%) 23 (92%)
5 (15%) 28 (82%) 1 (3%)
94 (25%) 225 (59%) 61 (16%)
P=0.001
14 (48%) 15 (52%) 0 (0%)
21 (84%) 4 (16%) 0 (0%)
19 (56%) 14 (41%) 1 (3%)
191 (51%) 181 (48%) 5 (1%)
P=0.054
1 3 12 13
1 2 4 18
2 1 11 20
6 18 106 250
P=0.975
a
"Other" diagnoses were excluded in statistical analysis because chi-squared does not support a zero value and COPD and IPF are far more common. b ”HLT” cases were excluded in statistical analysis because SLT and DLT were far more common and more useful metrics of comparison.
Displays the basic demographic information as well as surgical metrics. P values are derived from Chi-squared analysis. CABG-Con, patients who underwent concomitant coronary artery grafting during lung transplantation. CABG-Pre, patients that underwent a CABG at some point prior to lung transplantation; COPD, Chronic obstructive pulmonary disease; CPB, cardiopulmonary bypass; DLT, double lung transplant; HLT, heart lung transplant; IPF, idiopathic pulmonary fibrosis; LAS, lung allocation score; LOS, length of stay; No Revas, patients that did not require revascularization; Off, off pump; PCI-Pre, patients that underwent percutaneous coronary intervention prior to lung transplantation; SLT, single lung transplant; VA ECMO, veno-arterial extracorporeal
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membrane oxygenation; VV ECMO, veno-venous extracorporeal membrane oxygenation.
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Table 2. Grafts Utilized in Concomitant CABG Graft Type
Instances
LIMA-LAD
22
LIMA-DIAG
1
SVG-PDA
5
SVG-RCA
5
SVG- OM
5
SVG-DIAG
3
SVG- LCX
1
SVG-LPL
1
SVG-LAD
1
Displays the grafts used in all concomitant coronary artery bypass performed. Diag, diagonal arteries; LAD, left anterior artery; LCX, left circumflex artery; LIMA, left internal mammary artery; LPL, left posterolateral; OM, obtuse marginal artery; PDA, posterior descending artery; RCA, right coronary artery; SVG; saphenous venous graft.
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Table 3. Grafts by Incision Type Incision Median Sternotomy
Antero-axillary Thoracotomy
Number of Patients 16
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Total Grafts per Grafts patient 24 1.8/2
Graft Types LIMA-LAD
Instances of Graft Type 14
12
SVG-OM SVG-RCA SVG-Diag SVG-PDA LIMA-DIAG SVG-LPL LIMA-LAD
3 1 1 3 1 1 6
1.3/1
SVG-OM 1 SVG-LCx 1 SVG-RCA 1 SVG_Diag 2 SVG-PDA 1 Clamshell 4 7 1.5/1.5 SVG-RCA 3 SVG-PDA 2 SVG-AM 1 AVG-LAD 1 Displays the types of grafts done under each incision type utilized in concomitant coronary artery bypass. Grafts per patient displays mean/median values. Diag, diagonal arteries; LAD, left anterior artery; LCX, left circumflex artery; LIMA, left internal mammary artery; LPL, left posterolateral; OM, obtuse marginal artery; PDA, posterior descending artery; RCA, right coronary artery; SVG; saphenous venous graft.
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Table 4. Postoperative MACCE and Revascularization Frequencies MACCE Revascularization P value PCI-Pre 17.2% 14.7% CABG-Pre 16.0% 12.0% P=0.892 CABG-Con 20.6% 13.8% Displays the rates of the revascularization and MACCE, defined as a composite of nonfatal stroke, nonfatal MI, and cardiovascular death. CABG-Con, patients who underwent concomitant coronary artery grafting during lung transplantation; CABG-Pre, patients that underwent a CABG at some point prior to lung transplantation; PCI-Pre, patients that underwent percutaneous coronary intervention prior to lung transplantation.
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Figure Legend Figure 1. Kaplan-Meier Curve comparing survival from Feb 2012- July 2019 in the 4 Lung Transplant Groups (last transplantation dated July 15, 2018). Additionally, survival function results are shown below. At current date, CABG-Con has 19 survivors, CABGPre has 14 survivors, PCI-Pre had 18 survivors, and No Revas had 273 survivors. The survival interquartile ranges for the four groups were 2.86, 2.38, 2.22, and 1.99 years, respectively. CABG-Con, patients who underwent concomitant coronary artery grafting during lung transplantation; CABG-Pre, patients that underwent a CABG at some point prior to lung transplantation; No Revas, patients that did not require revascularization; PCI-Pre, patients that underwent percutaneous coronary intervention prior to lung transplantation.
20
S0003-4975(20)30229-0
DOI:
https://doi.org/10.1016/j.athoracsur.2020.01.016
Reference:
ATS 33502
To appear in:
The Annals of Thoracic Surgery
Received Date: 11 February 2019 Revised Date:
8 January 2020
Accepted Date: 9 January 2020
Please cite this article as: Kanaparthi J, Kashem MA, Suryapalam M, Zhao H, Brann S, Leotta E, Minakata K, Keshavamurthy S, Shigemura N, Toyoda Y, Prior and peri-operative revascularization does not affect survival in lung transplant patients, The Annals of Thoracic Surgery (2020), doi: https:// doi.org/10.1016/j.athoracsur.2020.01.016. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. 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. © 2020 by The Society of Thoracic Surgeons
Prior and peri-operative revascularization does not affect survival in lung transplant patients Reading Head: PCI, CABG, Concomitant CABG in Lung Tx
Jay Kanaparthi1 BS, Mohammed A Kashem MD2, PhD, Manish Suryapalam3, Huaqing Zhao2 PhD, Stacey Brann2 MD, Eros Leotta2 MD, Kenji Minakata2 MD, Suresh Keshavamurthy3 MD, Norihisa Shigemura2 MD, Yoshiya Toyoda2 MD, PhD
1
Lewis Katz School of Medicine at Temple University, 3500 N Broad Street, Philadelphia,
PA, 19140; 2Division of Cardiovascular Surgery, Temple University Medical Center, 3401 N Broad Street, Suite 301 Zone C, Philadelphia, PA, 19140; 3Temple University, 1801 N Broad St, Philadelphia, PA 19122; 4Division of Cardiothoracic Surgery, University of Kentucky, 740 S. Limestone, Lexington, KY 40536
Classifications: Coronary artery bypass grafts, CABG Coronary stents, PCI Revascularization Statistics, survival analysis Transplantation, lung Word Count: 4246
Corresponding Author: Yoshiya Toyoda MD, PhD 3401 N Broad Street, Suite 301 Zone C, Philadelphia, PA, 19140 [email protected]
1
Abstract Background: Coronary artery disease is common in lung transplant patients and has historically been viewed as a contraindication to the procedure. Although this mindset is changing, the effect of prior or peri-operative revascularization on lung transplant survival outcomes is not adequately established. Methods: We performed a single-center retrospective analysis of all single and double lung transplant patients from 2012-2018 (n=468). Patients were split into four groups: 1) patients that received a pre-operative PCI (n=34), 2) patients that received coronary artery bypass grafting prior to transplantation (n=25), 3) patients that received concomitant coronary artery bypass grafting during transplantation (n=29), and 4) patients that had lung transplantation with no need for revascularization (n=380). Groups were compared for demographics, surgical procedure, and survival outcomes. Results: The no revascularization group was statistically younger than the rest (p=0.001). The lung allocation score trended towards being higher in the concomitant coronary artery byspass (p=0.03). All groups were predominantly diagnosed with IPF. The proportion of patients with COPD was greatest in the group not requiring revascularization (p=0.001). Patients with previous coronary artery bypass grafting were more likely to receive a single lung transplant than a double (21 vs 4, P=0.054). Length of stay, post-transplant survival, and postoperative adverse events were similar amongst all groups. Conclusions: Results suggest preoperative or intraoperative revascularization does not negatively impact survival in lung transplant patients; lung recipients with coronary artery disease have comparable survival when adequately revascularized.
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Lung transplantation (LTx) is a crucial therapy for an array of end-stage lung diseases. To date, over 50,000 lung transplants have occurred, and the relative increase in lung transplants exceeds that of any other organ transplant over the last 10 years [1,2]. As operative techniques and peri-transplant care have developed over the last several decades, post-transplant outcomes have naturally increased. Thus, patients historically considered ineligible for LTx can now qualify to be lung recipients. Although survival rates are increasing, graft failure, infection, multiple organ failure, and cardiovascular disease remain significant causes of death. Cardiovascular causes of death lead to 11.6% of deaths within the first month of transplant and 7% of deaths beyond 10 years [1]. Coronary artery disease (CAD) historically was a contraindication to LTx, but recently was redefined as a relative contraindication [3]. Existing CAD is thought to pose a health risk for transplant patients because long-term immunosuppression can promote further atherosclerosis. Therapies for CAD in general populations include revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Several studies show that PCI and CABG show similar outcomes, but PCI is generally associated with increased need for repeat revascularization, and CABG shows better outcomes in multivessel disease and more complicated, non-linear atherosclerotic buildup [4,5,6] For potential lung transplant recipients with CAD, revascularization options include PCI or CABG prior to transplant or concomitant CABG during the transplantation. Transplant patients with less severe CAD may be deemed amenable to pre-transplant PCI. However, revascularization with PCI may not be a good option when the anatomy of the stenosis is not favorable for PCI, as seen in left main disease, bifurcating lesions, occluded lesions, etc. These cases may benefit from concomitant CABG because of the long-term benefit of left internal mammary artery-left anterior descending coronary artery
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bypass grafting and multi-vessel bypasses over PCI. Decisions regarding patient viability for revascularization and type of technique are left to the discretion of transplant centers as per the 2014 ISHLT Pulmonary Transplant consensus report [3]. Some studies suggest that concomitant CABG with LTx has demonstrated similar outcomes to LTx [7,8,9]. However, the long-term survival in these patients has still not been adequately established. In this study, we analyzed all lung transplant recipients at our institution over the past 6 years to compare survival outcomes of patients that have received a preoperative PCI, pre-operative CABG, concomitant CABG, or did not require revascularization.
Patients and Methods This study has been approved by the regulatory institutional review board of the Temple University Health System. We performed a single center review of all single and double lung transplant patients who underwent LTx at our center from February 2012 to August 2018. Patients were sorted into four groups: 1) patients that had received a preoperative PCI, 2) patients that had received coronary artery bypass grafting prior to transplantation, 3) patients that had received concomitant coronary artery bypass grafting during transplantation, and 4) patients that had lung transplantation with no need for revascularization. At our center, patients with severe coronary artery disease with no other major contraindications were accepted for either concomitant CABG or pre-operative PCI. We define significant CAD by a positive fractional flow reserve (FFR) less than 0.8 or or instantaneous wave-free ration (iFR) less than 0.9. Preoperative PCIs were performed by interventional cardiologists using balloon catheterization and drug-eluting stents. When patients were deemed anatomically not amenable to PCI, concomitant CABG was
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considered. Many of the CABGs performed prior to transplants were performed at other centers prior to the transplant referral at our center. Our strategy was to perform single lung transplantation in the chest contralateral to patent IMA graft.
Statistical Analysis Data were expressed as mean ± standard deviation or median where applicable for continuous variables and frequencies with percentages for categorical variables. The cohorts were compared for a number of parameters such as lung allocation score (LAS), length of stay (LOS), major adverse cardiac and cerebrovascular event (MACCE) rates, revascularization following transplant, incision type, grafts used, age, pump, and, most importantly, survival time. All scalar variables, which consisted of age, ischemic time, LOS, and LAS, were analyzed, pooled over strata by a Kruskal-Wallis one-way ANOVA test due to the non-normality. Ischemic time and LOS were additionally assessed pairwise over strata for significance. Only the No Revas cohort was nonnormal for ischemic time, so pairwise analysis was performed using Mann-Whitney UTests for pairs including the No Revas cohort and ANOVA with post-hoc Tukey’s HSD for pairs excluding the No Revas cohort. For LOS, all pairwise comparisons were assessed using Mann-Whitney U-Tests due to non-normality in all cohorts. Survival data were assessed by Kaplan-Meier curve and compared by Breslow, Tarone-Ware, and log-rank tests pooled over strata in order to assess significance at earlier, middle, and later points in the time course. Survival was confirmed in all patients since the closing of the study, and no patients were lost to follow-up. Hence, analysis of completeness of follow-up was not performed. Further analysis was performed pairwise over strata. Cox Regression was then performed using variables with statistically significantly different distributions across the four cohorts, which consisted of age, LAS, diagnosis, and
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gender. A p-value less than 0.05 was considered statistically significant. All the data were analyzed using SPSS 25.0 (IBM Corp., Aramonk, NY).
Results Of the patients analyzed, 34 required preoperative PCI, 25 received previous CABG, 29 required concomitant CABG, and 380 did not require revascularization (Table 1). There was a significant difference in recipient age between the groups (p=0.001), which was primarily driven by the distribution in age of the No Revas cohort, especially in comparison to the CABG-Pre cohort (p=0.006). Patients with no revascularization were the youngest, whereas patients with CABG prior to transplantation were the oldest. The cohorts showed no statistical difference in LOS, ischemic time, CPB time, or pump (Table 1). The most common diagnoses requiring lung transplantation at our center were idiopathic pulmonary fibrosis (IPF, 64%), followed by chronic obstructive pulmonary disease (COPD, 22%). There was significant difference in diagnosis between groups with the relative higher ratio of patients with COPD in the group not requiring revascularization (p=0.001). Other less common diagnoses included sarcoidosis, obliterative bronchiolitis, bronchiolitis obliterans with organizing pneumonia, bronchiectasis, alpha-1-antitrypsin deficiency, pulmonary hypertension, scleroderma, Sjogren's syndrome, and pulmonary fibrosis. The rates of single and double lung transplants were similar in all groups except in the group that had previously undergone CABG. This group was more likely to receive a single lung transplant over a double (21 vs 4, P=0.003) because of our strategy to avoid performing lung transplant in the chest ipsilateral to patent internal mammary grafts. This group was the primary contributor to our relatively low p value for single vs. double lung transplant (p=0.054), although it still did not reach statistical significance.
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In patients with concomitant CABG, the number of bypass grafts ranged from 1 to 3 (mean 1.6 ± 0.6). CABG was done using saphenous venous grafts and/or left internal mammary arteries (Table 2). The most common conduit utilized was LIMA-LAD whereas the most common venous graft was SVG-PDA (Table 2). 15 of the concomitant patients needed more than one graft (grafts=32: mean 2.1 median: 2). Median sternotomy (grafts=24: mean 1.8 median: 2), antero-axillary thoracotomy (grafts=12: mean 1.3 median: 1), and clamshell approach (grafts=7: mean 1.5 median: 1.5) were used while performing lung transplantation and CABG concomitantly (Table 3). Surgical exposure to the lung and coronary arteries was considered when determining surgical approach. Concomitant CABG with median sternotomies involved left internal mammary artery (LIMA) graft in all but one instance, whereas saphenous vein grafts were the exclusive conduits when a clamshell incision was used. The antero-axillary approach included both methods of grafting.
The mean times from revascularization to lung transplantation in the CABG-Pre and PCI-Pre cohort were 4.0±4.1 and 7.8±6.4 years respectively and the median times were 3 and 4.5 years respectively between revascularization and transplant, which showed a statistically significant difference (p=0.015). We routinely perform off pump lung transplantation. However, when patients are on ECMO preoperatively, we continue to use ECMO intraoperatively. When we need to initiate pump intraoperatively, we use either cardiopulmonary bypass or veno-arterial ECMO. In patients with concomitant CABG, we utilized cardiopulmonary bypass (n=12), veno-venous ECMO (n= 1), or veno-arterial ECMO (n= 3) intra-operatively for both concomitant and regular lung transplantation. However, all concomitant CABGs were performed on a beating heart without cardioplegic arrest.
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Assessment of the primary graft dysfunction (PGD) rate in the CABG-Con showed ten patients had a PGD Grade of 0, four had a PGD grade of 1, three had a PGD grade of 2, and twelve had a PGD grade of 3. Additionally, post-operative MACCE and revascularization rates are shown in Table 4. There was no significant difference between groups, which is promising but may be due to the small sample size of each group. Kaplan-Meier analysis was performed using Breslow (p=0.668), Tarone-Ware (p=0.429), and Log-Rank (p=0.186) tests pooled over strata in order to assess significance at earlier, middle, and later points in the time course. All three tests indicated that the difference between the survival rates of the four cohorts was statistically insignificant. Further analysis was performed pairwise over strata, but still revealed no significant difference in survival rate. A cox regression was then performed with variables determined to have a statistically significant difference in distribution between cohorts, which consisted of age, LAS, diagnosis, and gender. These produced p values of 0.751, 0.582, 0.611, and 0.119 respectively, as well as an overall p value of 0.593 for the regression. As indicated by the p-values, none of these variables were determined to have a statistically significant effect on lung transplant survival.
Comment The results of this study suggest that lung transplant patients with past coronary revascularization or concomitant revascularization demonstrate similar outcomes to other lung transplant patients. This supports the idea that patients with history of CAD or coronary revascularization procedures (PCI or CABG) can be considered for lung transplantations. Additionally, patients seeking lung transplantation with severe stenosis not amenable to PCI may pursue concomitant CABG and lung transplantation with no statistical change in survival.
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Our results suggest patients with coronary artery disease that received revascularization show similar rates of survival to those that do not require revascularization. This is in concordance with previous studies. Zanotti et al. compared lung transplant outcomes in 362 patients without CAD and 177 with moderate CAD and determined that moderate CAD did not increase peri-operative morbidity or decrease survival [10]. However, their analysis did not include patients with prior revascularization surgeries or patients with severe CAD (occlusion >70%), which are included in our study. Chaikriangkai et al. also found that preoperative coronary artery disease did not increase mortality risk but suggested that subsequent nonfatal cardiovascular events were increased, with a 12% annualized rate of post-transplant vascular events for patients with significant CAD vs 1% in patients with mild or no CAD [8]. Our study did not find an increase in acute cardiovascular events in this group. Koprivanac et al. performed a 1:1 matched analysis of 61 patients with CAD that had undergone revascularization with patients with mild to no CAD (<50% stenosis) and found no difference in post-transplant survival [11]. More recently, Mackey et al. did not find a statistically difference in survival probability in patients with CAD and patients without CAD (p=0.08) [9]. Additionally, they found that incidences of cardiac causes of death were rare in CAD patients receiving lung transplantation (2 of 56 deaths). Our paper corroborates these findings through survival and MACCE analysis. Concomitant CABG could not be studied in this analysis by Mackey et al., as none were performed during their study period. Support for revascularization with lung transplantation has been suggested by several papers [12,13]. Sherman et al. compared 27 lung recipients that had undergone PCI or concomitant CABG with 81 control recipients, and much like our paper, demonstrated similar survival and peri-operative adverse events in the two groups [7]. Parekh et al. found that in lung transplant with concomitant cardiac procedures,
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predominantly foramen ovale or atrial septal defect surgeries, similar 5-year survival was observed as compared to patients without these concomitant procedures [12]. In two more recent papers, Castleberry et al. and Biniwale et al. also examined concomitant cardiac surgery (CCS), with the former focusing more on PCI and CABG. Both found similar rates of survival as well as outcomes amongst CCS and non-CCS lung transplant groups. Castleberry et al. reported longer duration of mechanical ventilation and length of stay in patients with concomitant surgery [13]. Conversely, Biniwale et al. suggested CCS does not negatively impact peri-operative care [14]. These authors suggested better selection in patients as the reason for their better outcomes. Our results also demonstrated similar outcomes, but unlike Castleberry et al. we showed no statistical difference in length of stay. Furthermore, our concomitant CABG patients were older and had higher LAS compared to our patients with no revascularization, which indicates that our concomitant CABG group were potentially sicker and more at-risk patients. Despite these factors, our CABG-Con group had excellent outcomes with no incidents of CVA or other ischemic events and 100% survival in the first year. Castleberry et al. also warned of the risks of performing concomitant CABG in patients over the age of 65. Although our analysis did not perform statistical analysis stratified for age, 15 out of 28 of our concomitant CABG group exceeded the age of 65 (7 patients were >70 years of age) and we observed comparable survival in this cohort, suggesting strong outcomes can be achieved with excellent intraoperative management by an experienced team. McKellar et al. analyzed United Network for Organ Sharing (UNOS) data to suggest that lung transplantation in patients with prior CABG demonstrated better outcomes with single lung transplant over double lung transplant [15]. We did not directly compare SLT and DLT in our study, because very few DLTs were performed in our CABG-pre group. We were wary of potential hazards of entering the ipsilateral chest to
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the patent internal mammary artery graft, and therefore we more selectively performed SLTs contralateral to the patent graft in these patients. Additionally, McKellar et al. found statistically different survival between transplant recipients with prior CABG and recipients with no prior CABG at all time points (30 days: 94% vs 97%, 1 yr: 80% vs 89%, 5 yr: 66% vs 70%; p < 0.01). This conflicts with our study. McKellar et al. has much greater statistical power due to the size of the UNOS registry (14,499 No CABG patients, 292 CABG patients). The difference may also be due to advancements in the procedure as McKellar et al. used UNOS data from 2004 to 2013, whereas our data was from 2012 to 2018. Additionally, the strong outcomes could be due to factors related to our experienced team’s management of transplants complicated by CAD and careful prevention of causing peri-operative cardiac events. However, this study, like many of its type, is somewhat limited in its statistical power due to the relative infrequency of concomitant CABG with lung transplantation. While this study tracked yearly survival over six years, more thorough analysis of medical condition post-surgery is warranted. We address survival and MACCE rates as determinants of success but do not more thoroughly assess quality of life or nonMACCE complications after discharge. Additionally, this study carries the typical confounders of a single center design. Our outcomes have the risk of not being broadly applicable, as factors such as surgeon skill and team efficiency vary from site to site. The historic apprehension to performing lung transplants in CAD patients was partly due to overall scarcity of organ pools. This body of research serves to add patients to the potential recipient pool, but we do acknowledge that efforts must be made to increase the overall potential donor pool. Thus, it is imperative that actions are taken to increase both the rate of donation and usability of existing organs through technological advancement, such as ex vivo perfusion.
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Overall, our study supports the inclusion of CAD patients in the lung transplant recipient pool. Additionally, it corroborates the growing notion that concomitant CABG is a viable option in the context of lung transplantation by an expert team. We hope our strong outcomes help motivate further use of the concomitant CABG procedure as well as consideration of CAD patients for transplants.
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References: 1. Yusen RD, Edwards LB, Dipchand AI, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Lung and Heart– Lung Transplant Report—2016; Focus Theme: Primary Diagnostic Indications for Transplant. J Heart Lung Transplant. 2016;35(10):1170-1184. 2. Adegunsoye A, Strek ME, Garrity E, et al. Comprehensive Care of the Lung Transplant Patient. Chest. 2017;152:150-64. 3. Weill D, Benden C, Corris P, et al. A consensus document for the selection of lung transplant candidates: 2014- An update from the pulmonary transplantation council of the international society for heart and lung transplantation. J Heart Lung Transplant. 2015;34:1-15. 4. Putzu A, Gallo M, Martino EA, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention with drug-eluting stents for left main coronary artery disease: A meta-analysis of randomized trials. Int J Cardiol 2017;241:1428. 5. Lee CW, Ahn JM, Cavalcante R, et al. Coronary Artery Bypass Surgery Versus Drug-Eluting Stent Implantation for Left Main or Multivessel Coronary Artery Disease: A Meta-Analysis of Individual Patient Data. JACC Cardiovasc Interv. 2016;9:2481-9. 6. Spadaccio C, Benedetto U. Coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) in the treatment of multivessel coronary disease: quo vadis? —a review of the evidences on coronary artery disease. Ann Cardiothorac Surg 2018;7(4):506-515. 7. Sherman W, Rabkin DG, Ross D, et al. Lung transplantation and coronary artery disease. Ann Thorac Surg 2011;92:303-308.
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8. Chaikriangkrai K, Jyothula S, Jhun HY, et al. Impact of pre-operative coronary artery disease on cardiovascular events following lung transplantation. J Heart Lung Transplant. 2016;35(1):115. 9. Makey IA, Sui JW, Huynh C, et al. Lung transplant patients with coronary artery disease rarely die of cardiac causes. Clin Transplant. 2018;32:e13354. 10. Zanotti G, Hartwig MG, Castleberry AW, et al. Preoperative mild- to-moderate coronary artery disease does not affect long-term out- comes of lung transplantation. Transplantation. 2014;97(10):1079. 11. Koprivanac M, Budev MM, Yun JJ, et al. How important is coronary artery disease when considering lung transplant candidates? J Heart Lung Transplant. 2016;35(12):1453. 12. Parekh K, Meyers BF, Patterson GA et al. Outcome of lung transplantation for patients requiring concomitant cardiac surgery. J Thorac Cardiovasc Surg 2005; 130: 859-863. 13. Castleberry AW, Martin JT, Osho AA, Hartwig MG, Hashmi ZA, Zanotti G, et al. Coronary revascularization in lung transplant recipients with concomitant coronary artery disease. Am J Transplant. 2013;13:2978-88. 14. Biniwale R, Ross D, Iyengar A, Kwon OJ, et al. Lung transplantation and concomitant cardiac surgery: Is it justified? J Thorac Cardiovasc Surg. 2016;151(2): 560-67 15. McKellar SH, Bowen ME, Baird BC, et al. Lung transplantation following coronary artery bypass surgeryimproved outcome following single-lung transplant. J Heart Lung Transplant. 2016;35(11):1289-94
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Table 1. Demographics and Surgical Procedure Factor Patient Age (years) Gender M F LAS LOS (days) Ischemic Time CPB Time Diagnoses COPD IPF Othera Single vs Double SLT DLT HLTb Pump VV ECMO VA ECMO CPB Off
CABG- Con 66 ± 5
CABG-Pre 69 ± 5
PCI-Pre 67 ± 6
No Revas 63 ± 10
P value P=0.001
25 4 58 ±21 27.1±6.1 261.2±23.2
20 5 51 ±18 23.4±6.3 294.5±23.1
31 3 56 ±21 36.79±8.7 272.0±24.6
229 151 50 ±20 30.3±2.1 255.1±7.0
P=0.000 P=0.030 P=0.334 P=0.563
190.9±62.6
132.7±72.7
199.3±63.1
193.9±65.6
P=0.481
3 (10%) 24 (83%) 2 (7%)
2 (8%) 23 (92%)
5 (15%) 28 (82%) 1 (3%)
94 (25%) 225 (59%) 61 (16%)
P=0.001
14 (48%) 15 (52%) 0 (0%)
21 (84%) 4 (16%) 0 (0%)
19 (56%) 14 (41%) 1 (3%)
191 (51%) 181 (48%) 5 (1%)
P=0.054
1 3 12 13
1 2 4 18
2 1 11 20
6 18 106 250
P=0.975
a
"Other" diagnoses were excluded in statistical analysis because chi-squared does not support a zero value and COPD and IPF are far more common. b ”HLT” cases were excluded in statistical analysis because SLT and DLT were far more common and more useful metrics of comparison.
Displays the basic demographic information as well as surgical metrics. P values are derived from Chi-squared analysis. CABG-Con, patients who underwent concomitant coronary artery grafting during lung transplantation. CABG-Pre, patients that underwent a CABG at some point prior to lung transplantation; COPD, Chronic obstructive pulmonary disease; CPB, cardiopulmonary bypass; DLT, double lung transplant; HLT, heart lung transplant; IPF, idiopathic pulmonary fibrosis; LAS, lung allocation score; LOS, length of stay; No Revas, patients that did not require revascularization; Off, off pump; PCI-Pre, patients that underwent percutaneous coronary intervention prior to lung transplantation; SLT, single lung transplant; VA ECMO, veno-arterial extracorporeal
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membrane oxygenation; VV ECMO, veno-venous extracorporeal membrane oxygenation.
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Table 2. Grafts Utilized in Concomitant CABG Graft Type
Instances
LIMA-LAD
22
LIMA-DIAG
1
SVG-PDA
5
SVG-RCA
5
SVG- OM
5
SVG-DIAG
3
SVG- LCX
1
SVG-LPL
1
SVG-LAD
1
Displays the grafts used in all concomitant coronary artery bypass performed. Diag, diagonal arteries; LAD, left anterior artery; LCX, left circumflex artery; LIMA, left internal mammary artery; LPL, left posterolateral; OM, obtuse marginal artery; PDA, posterior descending artery; RCA, right coronary artery; SVG; saphenous venous graft.
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Table 3. Grafts by Incision Type Incision Median Sternotomy
Antero-axillary Thoracotomy
Number of Patients 16
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Total Grafts per Grafts patient 24 1.8/2
Graft Types LIMA-LAD
Instances of Graft Type 14
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SVG-OM SVG-RCA SVG-Diag SVG-PDA LIMA-DIAG SVG-LPL LIMA-LAD
3 1 1 3 1 1 6
1.3/1
SVG-OM 1 SVG-LCx 1 SVG-RCA 1 SVG_Diag 2 SVG-PDA 1 Clamshell 4 7 1.5/1.5 SVG-RCA 3 SVG-PDA 2 SVG-AM 1 AVG-LAD 1 Displays the types of grafts done under each incision type utilized in concomitant coronary artery bypass. Grafts per patient displays mean/median values. Diag, diagonal arteries; LAD, left anterior artery; LCX, left circumflex artery; LIMA, left internal mammary artery; LPL, left posterolateral; OM, obtuse marginal artery; PDA, posterior descending artery; RCA, right coronary artery; SVG; saphenous venous graft.
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Table 4. Postoperative MACCE and Revascularization Frequencies MACCE Revascularization P value PCI-Pre 17.2% 14.7% CABG-Pre 16.0% 12.0% P=0.892 CABG-Con 20.6% 13.8% Displays the rates of the revascularization and MACCE, defined as a composite of nonfatal stroke, nonfatal MI, and cardiovascular death. CABG-Con, patients who underwent concomitant coronary artery grafting during lung transplantation; CABG-Pre, patients that underwent a CABG at some point prior to lung transplantation; PCI-Pre, patients that underwent percutaneous coronary intervention prior to lung transplantation.
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Figure Legend Figure 1. Kaplan-Meier Curve comparing survival from Feb 2012- July 2019 in the 4 Lung Transplant Groups (last transplantation dated July 15, 2018). Additionally, survival function results are shown below. At current date, CABG-Con has 19 survivors, CABGPre has 14 survivors, PCI-Pre had 18 survivors, and No Revas had 273 survivors. The survival interquartile ranges for the four groups were 2.86, 2.38, 2.22, and 1.99 years, respectively. CABG-Con, patients who underwent concomitant coronary artery grafting during lung transplantation; CABG-Pre, patients that underwent a CABG at some point prior to lung transplantation; No Revas, patients that did not require revascularization; PCI-Pre, patients that underwent percutaneous coronary intervention prior to lung transplantation.
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