Cardiac allograft vasculopathy after heart transplantation: summary of a single-center long-term follow-up experience in Fuwai Hospital
-
摘要:
目的 总结心脏移植术后心脏移植物血管病变(CAV)的发生情况及其对患者长期存活的影响。 方法 回顾性分析1 006例心脏移植受者的临床资料,48例CAV患者中4例因缺失影像学证据未纳入分析。1 002例受者中,根据CAV发生情况分为CAV组(44例)和无CAV组(958例)。总结CAV的发生情况,比较两组患者的临床资料,分析CAV患者的影像学诊断方式及冠状动脉病变情况、药物治疗及合并症情况、术后生存情况及死亡原因。 结果 1 006例心脏移植受者中共48例发生CAV,发生率为4.77%。与无CAV组比较,CAV组患者术前吸烟史、术前高血压病史、原发病为冠状动脉疾病及围手术期感染的比例均较高(均为P < 0.05)。44例通过影像学诊断CAV的患者中,24例通过冠状动脉CT血管造影(CTA)诊断CAV,4例通过冠状动脉造影(CAG)诊断CAV,16例联合使用冠状动脉CTA及CAG诊断CAV。44例患者中,CAV 1级占45%(20/44),CAV 2级占30%(13/44),CAV 3级占25%(11/44)。全部患者术后长期使用他汀类药物治疗,有20例患者应用抗血小板药物治疗。44例CAV患者中,11例患者接受经皮冠状动脉介入治疗,6例患者接受再次心脏移植,共8例患者死亡。Kaplan-Meier生存分析结果显示,CAV组和无CAV组患者术后长期生存率差异无统计学意义(P > 0.05),但在诊断CAV后(术后6~7年),患者的生存率呈下降的趋势;CAV 1级、CAV 2级和CAV 3级患者术后长期生存率差异无统计学意义(P > 0.05),但即使是病变较轻的CAV 1级患者,术后远期生存率也呈下降趋势。 结论 CAV是心脏移植术后常见且棘手的并发症,诊断CAV后患者长期生存率呈下降趋势。应提高对CAV的认识,早预防、早诊断、早治疗,以提高患者心脏移植术后的长期生存率。 -
关键词:
- 心脏移植 /
- 心脏移植物血管病变(CAV) /
- 远期并发症 /
- 冠状动脉CT血管造影 /
- 冠状动脉造影(CAG) /
- 血管内超声(IVUS) /
- 经皮冠状动脉介入治疗(PCI) /
- 冠状动脉旁路移植术(CABG)
Abstract:Objective To summarize the incidence of cardiac allograft vasculopathy (CAV) after heart transplantation and the effect on the long-term survival of recipients. Methods Clinical data of 1 006 heart transplant recipients were retrospectively analyzed. Of 48 CAV patients, 4 cases were not included in this analysis due to lack of imaging evidence. A total of 1 002 recipients were divided into the CAV group (n=44) and non-CAV group (n=958) according to the incidence of CAV. The incidence of CAV was summarized. Clinical data of all patients were statistically compared between two groups. Imaging diagnosis, coronary artery disease, drug treatment and complications, postoperative survival and causes of death of CAV patients were analyzed. Results Among 1 006 heart transplant recipients, 48 cases (4.77%) developed CAV. Compared with the non-CAV group, the proportion of preoperative smoking history, preoperative hypertension history, coronary artery disease and perioperative infection was significantly higher in the CAV group (all P < 0.05). Among 44 patients diagnosed with CAV by imaging examination, 24 cases were diagnosed with CAV by coronary CT angiography (CTA), 4 cases by coronary angiography (CAG), and 16 cases by coronary CTA combined with CAG. Among 44 patients, the proportion of grade Ⅰ CAV was 45% (20/44), 30% (13/44) for grade Ⅱ CAV and 25% (11/44) for grade Ⅲ CAV, respectively. All patients received long-term use of statins after operation, and 20 patients were given with antiplatelet drugs. Among 44 CAV patients, 11 patients underwent percutaneous coronary intervention, 6 cases received repeated heart transplantation, and 8 patients died. Kaplan-Meier survival analysis demonstrated that there was no significant difference in the long-term survival rate between the CAV and non-CAV groups (P > 0.05), whereas the survival rate of patients tended to decline after the diagnosis of CAV (at postoperative 6-7 years). The long-term survival rates of patients with grade Ⅰ, grade Ⅱ and grade Ⅲ CAV showed no significant difference (P > 0.05). Even for patients with grade Ⅰ CAV, the long-term survival rate tended to decline. Conclusions CAV is a common and intractable complication following heart transplantation, and the long-term survival rate of patients after the diagnosis of CAV tended to decline. Deepening understanding of CAV, prompt prevention, diagnosis and treatment should be delivered to improve the long-term survival rate of patients after heart transplantation. -
表 1 两组患者的临床资料比较
Table 1. Comparison of clinical data of patients between two groups
指标 CAV组(n=44) 无CAV组(n=958) P值 受者资料 年龄(x±s,岁) 42±12 46±14 0.06 性别[n(%)] 男 37(84) 747(78) 0.33 女 7(16) 211(22) 体质量指数(x±s,kg/m2) 22±4 22±4 0.73 吸烟史[n(%)] 24(55) 329(34) < 0.01 糖尿病病史[n(%)] 8(18) 156(16) 0.74 高血压病史[n(%)] 7(16) 95(10) 0.01 原发病[n(%)] < 0.01 原发性心肌病 25(57) 694(72) 冠状动脉疾病 13(30) 139(15) 瓣膜病 2(5) 35(4) 先天性心脏病 2(5) 12(1) 其他 2(5) 78(8) 供者资料 年龄(x±s,岁) 32±9 33±10 0.57 冷缺血时间(x±s,min) 315±140 303±116 0.18 围手术期资料 使用机械辅助[n(%)] 5(11) 170(18) 0.14 感染[n(%)] 14(32) 127(13) < 0.01 -
[1] HAYES D JR, CHERIKH WS, CHAMBERS DC, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: twenty-second pediatric lung and heart-lung transplantation report-2019; focus theme: donor and recipient size match[J]. J Heart Lung Transplant, 2019, 38(10): 1015-1027. DOI: 10.1016/j.healun.2019.08.003. [2] ROSSANO JW, CHERIKH WS, CHAMBERS DC, et al. The Registry of the International Society for Heart and Lung Transplantation: twentieth pediatric heart transplantation report-2017; focus theme: allograft ischemic time[J]. J Heart Lung Transplant, 2017, 36(10): 1060-1069. DOI: 10.1016/j.healun.2017.07.018. [3] SPARTALIS M, SPARTALIS E, TZATZAKI E, et al. Cardiac allograft vasculopathy after heart transplantation: current prevention and treatment strategies[J]. Eur Rev Med Pharmacol Sci, 2019, 23(1): 303-311. DOI: 10.26355/eurrev_201901_16777. [4] ZHOU L, WOLFSON A, VAIDYA AS. Noninvasive methods to reduce cardiac complications postheart transplant[J]. Curr Opin Organ Transplant, 2022, 27(1): 45-51. DOI: 10.1097/MOT.0000000000000953. [5] SPARTALIS M, SPARTALIS E, SIASOS G. Cardiac allograft vasculopathy after heart transplantation: pathophysiology, detection approaches, prevention, and treatment management[J]. Trends Cardiovasc Med, 2021, DOI: 10.1016/j.tcm.2021.07.002 [Epub ahead of print]. [6] LEE F, NAIR V, CHIH S. Cardiac allograft vasculopathy: insights on pathogenesis and therapy[J]. Clin Transplant, 2020, 34(3): e13794. DOI: 10.1111/ctr.13794. [7] SINGH TP, CHERIKH WS, HSICH E, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: twenty-fourth pediatric heart transplantation report-2021; focus on recipient characteristics[J]. J Heart Lung Transplant, 2021, 40(10): 1050-1059. DOI: 10.1016/j.healun.2021.07.022. [8] 中华医学会器官移植学分会. 中国心脏移植术后随访技术规范(2019版)[J/CD]. 中华移植杂志(电子版), 2019, 13(1): 24-27. DOI: 10.3877/cma.j.issn.1674-3903.2019.01.006.Branch of Organ Transplantation of Chinese Medical Association. Technical specifications for follow-up after heart transplantation in China (2019 edition)[J/CD]. Chin J Transplant (Electr Edit), 2019, 13(1): 24-27. DOI: 10.3877/cma.j.issn.1674-3903.2019.01.006. [9] MEHRA MR, CRESPO-LEIRO MG, DIPCHAND A, et al. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010[J]. J Heart Lung Transplant, 2010, 29(7): 717-727. DOI: 10.1016/j.healun.2010.05.017. [10] NIKOLOVA AP, KOBASHIGAWA JA. Cardiac allograft vasculopathy: the enduring enemy of cardiac transplantation[J]. Transplantation, 2019, 103(7): 1338-1348. DOI: 10.1097/TP.0000000000002704. [11] MEHRA MR. The scourge and enigmatic journey of cardiac allograft vasculopathy[J]. J Heart Lung Transplant, 2017, 36(12): 1291-1293. DOI: 10.1016/j.healun.2017.10.010. [12] PIGHI M, GRATTA A, MARIN F, et al. Cardiac allograft vasculopathy: pathogenesis, diagnosis and therapy[J]. Transplant Rev (Orlando), 2020, 34(4): 100569. DOI: 10.1016/j.trre.2020.100569. [13] RAM E, LAVEE J, FREIMARK D, et al. Improved long-term outcomes after heart transplantation utilizing donors with a traumatic mode of brain death[J]. J Cardiothorac Surg, 2019, 14(1): 138. DOI: 10.1186/s13019-019-0963-2. [14] PAZDERNIK M, BEDANOVA H, CHEN Z, et al. Donor specific anti-HLA antibodies and cardiac allograft vasculopathy: a prospective study using highly automated 3-D optical coherence tomography analysis[J]. Transpl Immunol, 2021, 65: 101340. DOI: 10.1016/j.trim.2020.101340. [15] OMRANI O, ALAWWAMI M, BURAIKI J, et al. Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after heart transplantation[J]. Ann Saudi Med, 2018, 38(2): 97-104. DOI: 10.5144/0256-4947.2018.97. [16] DAS BB, PRUSTY BK, NIU J, et al. Cytomegalovirus infection and allograft rejection among pediatric heart transplant recipients in the era of valganciclovir prophylaxis[J]. Pediatr Transplant, 2020, 24(8): e13750. DOI: 10.1111/petr.13750. [17] KLIMCZAK-TOMANIAK D, ROEST S, BRUGTS JJ, et al. The association between cytomegalovirus infection and cardiac allograft vasculopathy in the era of antiviral valganciclovir prophylaxis[J]. Transplantation, 2020, 104(7): 1508-1518. DOI: 10.1097/TP.0000000000003015. [18] POTENA L, VALANTINE HA. Cytomegalovirus-associated allograft rejection in heart transplant patients[J]. Curr Opin Infect Dis, 2007, 20(4): 425-431. DOI: 10.1097/QCO.0b013e328259c33b. [19] COSTANZO MR, DIPCHAND A, STARLING R, et al. The International Society of Heart and Lung Transplantation guidelines for the care of heart transplant recipients[J]. J Heart Lung Transplant, 2010, 29(8): 914-956. DOI: 10.1016/j.healun.2010.05.034. [20] KURODA K, SUNAMI H, MATSUMOTO Y, et al. Percutaneous coronary intervention and coronary artery bypass grafting in heart transplant recipients with transplant coronary arterial vasculopathy[J]. Transplant Proc, 2017, 49(1): 130-134. DOI: 10.1016/j.transproceed.2016.11.006. [21] ZAKLICZYNSKI M, BABINSKA A, FLAK B, et al. Persistent mild lesions in coronary angiography predict poor long-term survival of heart transplant recipients[J]. J Heart Lung Transplant, 2014, 33(6): 618-623. DOI: 10.1016/j.healun.2013.10.029. [22] LU WH, PALATNIK K, FISHBEIN GA, et al. Diverse morphologic manifestations of cardiac allograft vasculopathy: a pathologic study of 64 allograft hearts[J]. J Heart Lung Transplant, 2011, 30(9): 1044-1050. DOI: 10.1016/j.healun.2011.04.008. [23] SEGURA AM, BUJA LM. Cardiac allograft vasculopathy: a complex multifactorial sequela of heart transplantation[J]. Tex Heart Inst J, 2013, 40(4): 400-402. [24] HUSAIN N, WATANABE K, BERHANE H, et al. Multi-parametric cardiovascular magnetic resonance with regadenoson stress perfusion is safe following pediatric heart transplantation and identifies history of rejection and cardiac allograft vasculopathy[J]. J Cardiovasc Magn Reson, 2021, 23(1): 135. DOI: 10.1186/s12968-021-00803-7. [25] NOUS FMA, ROEST S, VAN DIJKMAN ED, et al. Clinical implementation of coronary computed tomography angiography for routine detection of cardiac allograft vasculopathy in heart transplant patients[J]. Transpl Int, 2021, 34(10): 1886-1894. DOI: 10.1111/tri.13973. [26] LUC JGY, CHOI JH, RIZVI SA, et al. Percutaneous coronary intervention versus coronary artery bypass grafting in heart transplant recipients with coronary allograft vasculopathy: a systematic review and Meta-analysis of 1, 520 patients[J]. Ann Cardiothorac Surg, 2018, 7(1): 19-30. DOI: 10.21037/acs.2018.01.10. [27] ULLAH W, THALAMBEDU N, ZAHID S, et al. Percutaneous coronary intervention in patients with cardiac allograft vasculopathy: a Nationwide Inpatient Sample (NIS) database analysis[J]. Expert Rev Cardiovasc Ther, 2021, 19(3): 269-276. DOI: 10.1080/14779072.2021.1882851. [28] LEE MS, LLURI G, FINCH W, et al. Role of percutaneous coronary intervention in the treatment of cardiac allograft vasculopathy[J]. Am J Cardiol, 2018, 121(9): 1051-1055. DOI: 10.1016/j.amjcard.2018.01.025. [29] HALLE AA 3RD, DISCIASCIO G, MASSIN EK, et al. Coronary angioplasty, atherectomy and bypass surgery in cardiac transplant recipients[J]. J Am Coll Cardiol, 1995, 26(1): 120-128. DOI: 10.1016/0735-1097(95)00124-i. [30] MUSCI M, PASIC M, MEYER R, et al. Coronary artery bypass grafting after orthotopic heart transplantation[J]. Eur J Cardiothorac Surg, 1999, 16(2): 163-168. DOI: 10.1016/s1010-7940(99)00207-9. [31] JOHNSON MR, AARONSON KD, CANTER CE, et al. Heart retransplantation[J]. Am J Transplant, 2007, 7(9): 2075-2081. DOI: 10.1111/j.1600-6143.2007.01902.x.