Association of cardiac disease with the risk of post-lung transplantation mortality in Chinese recipients aged over 65 years

doi:10.1007/s11684-022-0937-y

Front. Med.

2023, Vol. 17

Issue (1) : 58-67 https://doi.org/10.1007/s11684-022-0937-y

RESEARCH ARTICLE

Association of cardiac disease with the risk of post-lung transplantation mortality in Chinese recipients aged over 65 years

Guohui Jiao, Shugao Ye, Ji Zhang, Bo Wu, Dong Wei, Dong Liu, Feng Liu, Chunxiao Hu, Jingyu Chen(

)

Wuxi Lung Transplant Center, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China

Download: PDF(3384 KB) HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

The current organ allocation rules prioritize elderly and urgent patients on the lung transplantation (LT) waiting list. A steady increase in the threshold at which age is taken into consideration for LT has been observed. This retrospective cohort study recruited 166 lung transplant recipients aged ≥ 65 years between January 2016 and October 2020 in the largest LT center in China. In the cohort, subgroups of patients aged 65–70 years (111 recipients, group 65–70) and ≥ 70 years (55 recipients, group ≥ 70) were included. Group D restrictive lung disease was the main indication of a lung transplant in recipients over 65 years. A significantly higher percentage of coronary artery stenosis was observed in the group ≥ 70 (30.9% vs. 14.4% in group 65–70, P = 0.014). ECMO bridging to LT was performed in 5.4% (group 65–70) and 7.3% (group ≥ 70) of patients. Kaplan–Meier estimates showed that recipients with cardiac abnormalities had a significantly increased risk of mortality. After adjusting for potential confounders, cardiac abnormality was shown to be independently associated with the increased risk of post-LT mortality (HR 6.37, P = 0.0060). Our result showed that LT can be performed in candidates with an advanced age and can provide life-extending benefits.

Keywords cardiac disease mortality aged population lung transplantation

Corresponding Author(s): Jingyu Chen

Just Accepted Date: 20 October 2022 Online First Date: 19 December 2022 Issue Date: 15 March 2023

Cite this article:

Guohui Jiao,Shugao Ye,Ji Zhang, et al. Association of cardiac disease with the risk of post-lung transplantation mortality in Chinese recipients aged over 65 years[J]. Front. Med., 2023, 17(1): 58-67.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-022-0937-y
https://academic.hep.com.cn/fmd/EN/Y2023/V17/I1/58

	Group 65–70 (N = 111)	Group ≥ 70 (N = 55)	Χ²/t	P
Gender, male, n (%)	96 (86.5)	51(92.7)	1.413	0.305
Age (year), mean ± SD	66.3 ± 1.4	72.5 ± 2.2
BMI at transplant (kg/m²), mean ± SD	21.95 ± 3.8	21.81 ± 3.5	0.203	0.840
Residency in Jiangsu Province, n (%)	30 (27.1)	22 (40)	4.623	0.036
Pretransplant tobacco use, n (%)	64 (57.7)	21 (38.2)	4.593	0.028
Primary diagnosis, n (%)			0.886	0.368
Group A obstructive lung disease	27 (24.3)	13 (23.6)
Group D restrictive lung disease	77 (69.4)	42 (76.4)
Others	7 (6.3)	0
Medical condition at transplantation, n (%)			2.195	0.334
In ICU	9 (8.1)	3 (5.5)
Hospitalized but not in ICU	99 (89.2)	48 (87.3)
Not hospitalized	3 (2.7)	4 (7.2)
NYHA Grade, n (%)
II	23 (20.7)	1 (1.8)
III	52 (46.8)	31(56.4)
IV	36 (32.4)	23 (41.8)
Cardiac vascular abnormality (CTA), n (%)			6.282	0.014
Medium and severe	16 (14.4)	17 (30.9)
Cardiac valve abnormality (chest echo), n (%)			2.593	0.118
Medium and severe	9 (8.1)	9 (16.4)
Mean PAP (mmHg), mean ± SD	58.2 ± 19.1	54.9 ± 11.2	1.073	0.286
LVEF value (%), mean ± SD	61.2 ± 3.7	60.4 ± 3.2	0.939	0.350
Chronic steroid use, n (%)	13 (11.7)	13 (23.6)	3.959	0.047
ECMO bridging, n (%)	6 (5.4)	4 (7.3)	0.227	0.732
Group D	6 (100)	4 (100)	0.227	0.732
Mechanical ventilation bridging, n (%)	2 (1.8)	2 (3.6)	0.526	0.6
Creatinine (μmol/L), mean ± SD	63.1 ± 16.9	60.4 ± 14.7	0.797	0.428
ALT (U/L), mean ± SD	24.9 ± 20.1	22.9 ± 11.1	0.512	0.525
Total bilirubin (μmol/L), mean ± SD	13.8 ± 7.9	14.6 ± 6.1	0.574	0.568
Pretransplant 6MWD (m), mean ± SD	183.6 ± 98.6	217.8 ± 83.9	1.089	0.288
6MWD not tolerated, n (%)	83(74.8)	44(80)	0.559	0.561
Hypertension, n (%)	34 (30.6)	23 (41.8)	5.792	0.018
Cardiac disease history, patient-reported, n (%)	31 (27.9)	23 (41.8)	7.603	0.009
Cerebral vascular disease, n (%)	3 (2.7)	3 (5.5)	0.799	0.399
Diabetes, n (%)	30 (27.0)	13 (23.6)	0.220	0.709
Pre-transplant pulmonary embolism, n (%)	3 (2.7)	4 (7.3)	1.902	0.221
CMV-IgG positive, n (%)	64 (57.7)	35 (63.6)	0.546	0.504
CMV-IgM positive, n (%)	1 (0.9)	3 (5.5)	3.243	0.107
EB-IgG positive, n (%)	34 (30.6)	18 (32.7)	0.075	0.859
Pulmonary infection need admission, n (%)	51 (45.9)	37 (67.3)	6.715	0.013

Tab.1 Recipient preoperative characteristics

Tab.2 Intraoperative characteristics

	Group 65–70 (N = 111)	Group ≥ 70 (N = 55)	Χ²/t	P
Drug-resistant bacterial infection, n (%)	101 (91)	52 (94.5)	0.644	0.548
Fungal infection, n (%)	46 (41.4)	32 (58.2)	4.138	0.048
Bronchostenosis, n (%)	19 (17.1)	9 (16.4)	0.015	0.903
Acute rejection, n (%)	8 (7.2)	10 (18.2)	4.582	0.038
Valve abnormality post-LT (chest echo), n (%)	23 (20.7)	19 (34.5)	3.719	0.060
Cardiac arrhythmia, n (%)	51 (45.9)	36 (65.5)	5.612	0.021
Cerebral dysfunction, n (%)	57 (51.4)	23 (41.8)	1.339	0.254
Delirium	14 (12.6)	6 (10.9)	0.101	0.751
Depression/anxiety	10 (9)	5 (9.1)	0.000	1.000
Change on cerebral imaging/electrophysiology	20 (18)	11 (20)	0.095	0.833
PGD (≥ grade 2 at 72 h), n (%)	64 (57.7)	32 (58.2)	0.004	0.949
Reintubation, n (%)	22 (19.8)	10 (18.2)	0.063	0.838
Pleural effusion, n (%)	31 (27.9)	33 (60)	15.969	0.000
Pulmonary embolism, n (%)	7 (6.3)	5 (9.1)	0.425	0.535
GERD, n (%)	12 (10.8)	1 (1.8)	4.120	0.062
Acute kidney injury, n (%)	29 (26.1)	17 (30.9)	0.420	0.582
Need CRRT in patients with AKI, n (%)	13 (44.8)	13 (76.5)	4.3672	0.064
Creatinine at 6 months (μmol/L), mean ± SD	66.7 ± 20.6	75.6 ± 13.7	0.856	0.409
Creatinine at 1 year (μmol/L), mean ± SD	98.2 ± 55.5	119.1 ± 23.3	0.871	0.398
Creatinine at 3 years (μmol/L), mean ± SD	81.3 ± 6.66	93.8 ± 18.5	1.102	0.332
Cyclosporine-based immunosuppression, n (%)	13 (11.7)	9 (16.4)	0.692	0.468
Tacrolimus-based immunosuppression, n (%)	59 (53.2)	27 (49.1)	0.243	0.742
Survival upon discharged, n (%)	91 (82)	45 (81.8)	0.001	0.979
Death, n (%)	38 (34.2)	27 (49.1)	3.407	0.091
Infection	18 (47.4)	12 (44.4)	0.054	0.816
Multiorgan dysfunction	8 (21.1)	8 (29.6)	0.626	0.561
Hemorrhage	5 (13.2)	0		0.061
Death in Diagnosis Group D, n (%)	25 (32.4)	21(50)	2.039	0.169
6 min walking distance (m, mean ± SD)	429 ± 82.5	370.3 ± 39.8	1.153	0.279
FEV1 (%) at 6 months, mean ± SD	63.5 ± 18.2	78.9 ± 20.5	2.408	0.021
FVC (%) at 6 months, mean ± SD	60.9 ± 16.1	67.5 ± 16.4	1.218	0.230
FEV1/FVC (%) at 6 months, mean ± SD	83.1 ± 10.5	87.5 ± 9.5	1.390	0.171
FEV1 (%) at 1 year, mean ± SD	69.1 ± 23.7	75.0 ± 16.8	0.770	0.448
FVC (%) at 1 year, mean ± SD	65.2 ± 21.1	68.2 ± 13.52	0.425	0.674
FEV1/FVC (%) at 1 year, mean ± SD	80.1 ± 11.9	84.1 ± 7.6	1.068	0.295
FEV1 (%) at 3 years, mean ± SD^a	75.2 ± 20.2	82.1 ± 15.3	0.740	0.469
FVC (%) at 3 years, mean ± SD^a	77.4 ± 15.2	74.5 ± 20.2	0.131	0.897
FEV1/FVC (%) at 3 years, mean ± SD^a	76.2 ± 12.4	84.1 ± 9.2	1.280	0.219
Confirmed diagnosis of CLAD at 3 years, n (%)	30 (27)	12(21.8)	0.528	0.467

Tab.3 Post-LT characteristics

Fig.1 Kaplan–Meier plot demonstrating time to death in lung transplant recipients stratified by age (A), cardiac abnormality (B), and NYHA Grade (C). The solid lines are the Kaplan–Meier survival estimates for each age group, and the shaded areas represent the 95% confidence bands. In the log-rank test, P value was used to compare the curves among the strata.

Tab.4 Relationship between cardiac abnormality and mortality in different models

Tab.5 Effect size of cardiac abnormality on mortality in subgroups

Fig.2 Cumulative rate of transplant strategy of bilateral/single-lateral LT and ECMO when considering main indications and cardiac abnormality.

1	DC Chambers, WS Cherikh, MO Harhay, D Jr Hayes, E Hsich, KK Khush, B Meiser, L Potena, JW Rossano, AE Toll, TP Singh, A Sadavarte, A Zuckermann, J; International Society for Heart Stehlik, Transplantation Lung. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: thirty-sixth adult lung and heart-lung transplantation report-2019; focus theme: donor and recipient size match. J Heart Lung Transplant 2019; 38(10): 1042–1055 https://doi.org/10.1016/j.healun.2019.08.001 pmid: 31548030
2	M Valapour, CJ Lehr, MA Skeans, JM Smith, E Miller, R Goff, J Foutz, AK Israni, JJ Snyder, BL Kasiske. OPTN/SRTR 2019 Annual Data Report: lung. Am J Transplant 2021; 21(Suppl 2): 441–520 https://doi.org/10.1111/ajt.16495 pmid: 33595190
3	A Courtwright, E Cantu. Lung transplantation in elderly patients. J Thorac Dis 2017; 9(9): 3346–3351 https://doi.org/10.21037/jtd.2017.08.31 pmid: 29221319
4	CL Mosher, JM Weber, CW Frankel, ML Neely, SM Palmer. Risk factors for mortality in lung transplant recipients aged ≥65 years: a retrospective cohort study of 5,815 patients in the scientific registry of transplant recipients. J Heart Lung Transplant 2021; 40(1): 42–55 https://doi.org/10.1016/j.healun.2020.10.009 pmid: 33208278
5	RD Yusen, LB Edwards, AI Dipchand, SB Goldfarb, AY Kucheryavaya, BJ Levvey, LH Lund, B Meiser, JW Rossano, J; International Society for Heart Stehlik, Transplantation Lung. 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 https://doi.org/10.1016/j.healun.2016.09.001 pmid: 27772669
6	J Kanaparthi, MA Kashem, M Suryapalam, H Zhao, S Brann, E Leotta, K Minakata, S Keshavamurthy, N Shigemura, Y Toyoda. Prior and perioperative revascularization does not affect survival in lung transplant patients. Ann Thorac Surg 2020; 109(6): 1677–1683 https://doi.org/10.1016/j.athoracsur.2020.01.016 pmid: 32105715
7	CX Hu, WH Chen, JX He, GN Jiang, XS Li, D Wei, B Wu, J Zhang, C Wang, JY Chen. Lung transplantation in China between 2015 and 2018. Chin Med J (Engl) 2019; 132(23): 2783–2789 https://doi.org/10.1097/CM9.0000000000000543 pmid: 31856048
8	B Wu, M Huang, G Jiao, C Hu, Y Yang, C; China Lung Transplantation Alliance; National Lung Transplantation Expert Group for COVID-19 Jingyu. Lung transplantation during the outbreak of coronavirus disease 2019 in China. J Thorac Cardiovasc Surg 2022; 163(1): 326–335.e6 https://doi.org/10.1016/j.jtcvs.2020.10.154 pmid: 33461803
9	B Wu, C Hu, W Chen, J He, G Jiang, J Zhang, D Liu, X Li, D Wei, G Jiao, C Wang, J Chen. China lung transplantation developing: past, present and future. Ann Transl Med 2020; 8(3): 41 https://doi.org/10.21037/atm.2019.10.26 pmid: 32154286
10	J Zhao, D Liu, J Huang, HC Jiang, Y Chen, HX Li, XS Li, JY Chen. The low utilization rate of donor lungs in China: a single-center experience. Ann Transplant 2021; 26: e931409 https://doi.org/10.12659/AOT.931409 pmid: 34373440
11	CJ Lehr, EH Blackstone, KR McCurry, L Thuita, WM Tsuang, M Valapour. Extremes of age decrease survival in adults after lung transplant. Chest 2020; 157(4): 907–915 https://doi.org/10.1016/j.chest.2019.06.042 pmid: 31419403
12	SD Nathan, N Weir, OA Shlobin, BA Urban, CA Curry, A Basavaraj, S Ahmad, J Kiernan, MJ Sheridan, JP Earls. The value of computed tomography scanning for the detection of coronary artery disease in patients with idiopathic pulmonary fibrosis. Respirology 2011; 16(3): 481–486 https://doi.org/10.1111/j.1440-1843.2010.01919.x pmid: 21199161
13	K Halloran, A Hirji, D Li, K Jackson, A Kapasi, S Meyer, J Mullen, D Lien, J Weinkauf. Coronary artery disease and coronary artery bypass grafting at the time of lung transplantation do not impact overall survival. Transplantation 2019; 103(10): 2190–2195 https://doi.org/10.1097/TP.0000000000002609 pmid: 30801514
14	C Spadaccio, U Benedetto. 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 https://doi.org/10.21037/acs.2018.05.17 pmid: 30094215
15	K Chaikriangkrai, S Jyothula, HY Jhun, J Estep, M Loebe, S Scheinin, G Torre-Amione. Impact of pre-operative coronary artery disease on cardiovascular events following lung transplantation. J Heart Lung Transplant 2016; 35(1): 115–121 https://doi.org/10.1016/j.healun.2015.08.009 pmid: 26452997
16	AW Castleberry, JT Martin, AA Osho, MG Hartwig, ZA Hashmi, G Zanotti, LK Shaw, JB Williams, SS Lin, RD Davis. Coronary revascularization in lung transplant recipients with concomitant coronary artery disease. Am J Transplant 2013; 13(11): 2978–2988 https://doi.org/10.1111/ajt.12435 pmid: 24102830
17	TJ Wallen, A Pelaez, S Chandrashekaran, AM Emtiazjoo, G Arnaoutakis, TN Machuca. Successful preoperative optimization for lung transplantation with transcatheter mitral valve repair. Ann Thorac Surg 2021; 111(3): e201–e203 https://doi.org/10.1016/j.athoracsur.2020.05.078 pmid: 32652070
18	BC Gulack, AM Ganapathi, PJ Speicher, JM Meza, SA Hirji, LD Snyder, RD Davis, MG Hartwig. What is the optimal transplant for older patients with idiopathic pulmonary fibrosis?. Ann Thorac Surg 2015; 100(5): 1826–1833 https://doi.org/10.1016/j.athoracsur.2015.05.008 pmid: 26210946
19	D Wei, F Gao, B Wu, M Zhou, J Zhang, H Yang, D Liu, L Fan, J Chen. Single versus bilateral lung transplantation for idiopathic pulmonary fibrosis. Clin Respir J 2019; 13(6): 376–383 https://doi.org/10.1111/crj.13020 pmid: 30916868
20	L Paglicci, V Borgo, N Lanzarone, M Fabbiani, C Cassol, MG Cusi, M Valassina, S Scolletta, E Bargagli, L Marchetti, P Paladini, L Luzzi, A Fossi, D Bennett, F Montagnani. Incidence and risk factors for respiratory tract bacterial colonization and infection in lung transplant recipients. Eur J Clin Microbiol Infect Dis 2021; 40(6): 1271–1282 https://doi.org/10.1007/s10096-021-04153-1 pmid: 33479881
21	SM Cho, S Farrokh, G Whitman, TP Bleck, RG Geocadin. Neurocritical care for extracorporeal membrane oxygenation patients. Crit Care Med 2019; 47(12): 1773–1781 https://doi.org/10.1097/CCM.0000000000004060 pmid: 31599814

[1]	FMD-22014-OF-CJY_suppl_1	Download
[2]	FMD-22014-OF-CJY_suppl_2	Download
[3]	FMD-22014-OF-CJY_suppl_3	Download

[1]	Usman Nasir Nakakana, Ridwan Muhammad Jega, Aliyu Mamman Nauzo, Yahya Mohammed, Ismaila Mohammed Ahmed. Cross-sectional prevalence and pattern of non-anaemia severe malaria among 2–10 year olds in Sokoto in Northwestern Nigeria[J]. Front. Med., 2022, 16(6): 969-974.
[2]	Shan Chong, Yun He, Yejun Wu, Peng Zhao, Xiaolu Zhu, Fengrong Wang, Yuanyuan Zhang, Xiaodong Mo, Wei Han, Jingzhi Wang, Yu Wang, Huan Chen, Yuhong Chen, Xiangyu Zhao, Yingjun Chang, Lanping Xu, Kaiyan Liu, Xiaojun Huang, Xiaohui Zhang. Risk stratification system for skin and soft tissue infections after allogeneic hematopoietic stem cell transplantation: PAH risk score[J]. Front. Med., 2022, 16(6): 957-968.
[3]	Yuling Yang, Xinnan Xu, Ming Liu, Yanfeng Zhao, Yongmei Yu, Xiaogang Liu, Chang Chen, Gening Jiang, Wenxin He. Outcomes of patients awaiting lung transplantation after the implementation of donation after brain death at a single Chinese center[J]. Front. Med., 2022, 16(5): 760-765.
[4]	Huai-yu Wang, Suyuan Peng, Zhanghui Ye, Pengfei Li, Qing Li, Xuanyu Shi, Rui Zeng, Ying Yao, Fan He, Junhua Li, Liu Liu, Shuwang Ge, Xianjun Ke, Zhibin Zhou, Gang Xu, Ming-hui Zhao, Haibo Wang, Luxia Zhang, Erdan Dong. Renin--angiotensin system inhibitor is associated with the reduced risk of all-cause mortality in COVID-19 among patients with/without hypertension[J]. Front. Med., 2022, 16(1): 102-110.
[5]	Junnan Liang, Guannan Jin, Tongtong Liu, Jingyuan Wen, Ganxun Li, Lin Chen, Wei Wang, Yuwei Wang, Wei Liao, Jia Song, Zeyang Ding, Xiao-ping Chen, Bixiang Zhang. Clinical characteristics and risk factors for mortality in cancer patients with COVID-19[J]. Front. Med., 2021, 15(2): 264-274.
[6]	Guohua Chen, Wen Su, Jiayao Yang, Dan Luo, Ping Xia, Wen Jia, Xiuyang Li, Chuan Wang, Suping Lang, Qingbin Meng, Ying Zhang, Yuhe Ke, An Fan, Shuo Yang, Yujiao Zheng, Xuepeng Fan, Jie Qiao, Fengmei Lian, Li Wei, Xiaolin Tong. Chinese herbal medicine reduces mortality in patients with severe and critical coronavirus disease 2019: a retrospective cohort study[J]. Front. Med., 2020, 14(6): 752-759.
[7]	Liya Ju, Caroline Suberbielle, Xiaofan Li, Nuala Mooney, Dominique Charron. HLA and lung transplantation[J]. Front. Med., 2019, 13(3): 298-313.
[8]	Fei Gao, Jingyu Chen, Dong Wei, Bo Wu, Min Zhou. Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation[J]. Front. Med., 2018, 12(2): 224-228.
[9]	Hualiang Lin,Bofu Ning,Jihua Li,Guangqiang Zhao,Yunchao Huang,Linwei Tian. Temporal trend of mortality from major cancers in Xuanwei, China[J]. Front. Med., 2015, 9(4): 487-495.
[10]	Zhe Zheng, Lu Zhang, Xi Li, Shengshou Hu, on behalf of the Chinese CABG Registry Study. SinoSCORE: a logistically derived additive prediction model for post-coronary artery bypass grafting in-hospital mortality in a Chinese population[J]. Front Med, 2013, 7(4): 477-485.

Viewed

Full text

Abstract

Cited

Shared

Discussed