Abstract
Background
Perioperative cardiovascular outcomes of transplant surgery are not well defined. We evaluated the incidence of perioperative major adverse cardiovascular and cerebrovascular events (MACCE) after non-cardiac transplant surgery from a large database of hospital admissions from the United States.
Methods
Patients ≥18 years of age undergoing non-cardiac solid organ transplant surgery from 2004 to 2014 were identified from the Healthcare Cost and Utilization Project’s National Inpatient Sample. The primary outcome was perioperative MACCE, defined as in-hospital death, myocardial infarction (MI), or ischaemic stroke.
Results
A total of 49 978 hospitalizations for transplant surgery were identified. Renal (67.3%), liver (21.6%), and lung (6.7%) transplantation were the most common surgeries. Perioperative MACCE occurred in 1539 transplant surgeries (3.1%). Recipients of organ transplantation were more likely to have perioperative MACCE in comparison to non-transplant, non-cardiac surgery [3.1% vs. 2.0%, P < 0.001; adjusted odds ratio (aOR) 1.29, 95% Confidence interval [CI] 1.22–1.36]. Major adverse cardiovascular and cerebrovascular events after transplant surgery were driven by increased mortality (1.7% vs. 1.1%, P < 0.001; aOR 1.15, 95% CI 1.07–1.23) and MI (1.2% vs. 0.6%, P < 0.001; aOR 2.26, 95% CI 2.09–2.46) vs. non-transplant surgery, with lower rates of stroke (0.3% vs. 0.5%, P < 0.001; aOR 0.56, 95% CI 0.47–0.65). Among patients hospitalized for renal, liver, and lung transplantation, MACCE occurred in 1.7%, 5.6%, and 7.5%, respectively, with no difference in the frequency of MI by surgery type.
Conclusions
Cardiovascular outcomes of transplant surgery vary by surgical subtype and are largely driven by increased perioperative death and MI. Efforts to reduce cardiovascular risks of non-cardiac organ transplant surgery are necessary.
Keywords: Acute coronary syndrome, Kidney, Liver, Lung, Myocardial infarction, Non-cardiac surgery, Perioperative, Renal, Surgery, Transplantation, Transplant surgery
Introduction
Transplant surgery is an important and potentially lifesaving therapeutic option for patients with irreversible end-organ disease, and more than 30 000 transplants are performed in the United States each year.1 Although outcomes of solid organ transplantation are generally favourable in the contemporary era, cardiovascular risk factors are increasingly common in transplant recipients, and major adverse cardiovascular and cerebrovascular events (MACCE) remain an important cause of perioperative morbidity and mortality.2–8 Given the scarcity of donated organs and challenges related to appropriate organ allocation, outcomes of transplant programs are subject to considerable scrutiny. Despite this, data on the perioperative cardiovascular outcomes of patients undergoing solid organ transplantation have not been systematically reported. We sought to evaluate the incidence of perioperative adverse cardiovascular events after non-cardiac solid organ transplant surgery from a large administrative database of hospital admissions from the United States.
Methods
Study population
Patients ≥18 years of age undergoing non-cardiac surgery from 2004 to 2014 were identified from the Healthcare Cost and Utilization Project’s (HCUP) National Inpatient Sample (NIS).9 The NIS is a national administrative database that contains discharge-level data for a 20% stratified sample of patients admitted to US hospitals.10 Patients were eligible for inclusion if the principal International Classification of Diseases, Ninth Revision (ICD-9) procedure code during hospital admission was a major therapeutic operating room procedure (HCUP Procedure Class 4).9 Patients who underwent cardiac transplantation, bone marrow transplantation, cardiac surgery, minimally invasive cardiac procedures, ophthalmologic surgery, dental surgery, radiation therapy, and non-operating room procedures were excluded from all analyses. Next, hospitalizations with and without non-cardiac solid organ transplant surgery were identified based on relevant ICD-9 procedure codes for lung transplant, liver transplant, renal transplant, intestinal transplant, pancreatic transplant, and spleen transplant surgery (Supplementary material online, Table S1).
In-hospital management and outcomes
The primary outcome was MACCE, defined as in-hospital death, myocardial infarction (MI), or ischaemic stroke. Perioperative MI was identified using ICD-9 diagnosis codes for acute ST-segment elevation myocardial infarction (STEMI) (410.01 to 410.61, 410.81, and 410.91) and non-ST-segment elevation myocardial infarction (NSTEMI) (410.71). Acute ischaemic stroke was identified using ICD-9 diagnosis codes 433.x1, 434.x1, 436, and 437.1.13. Other cardiovascular outcomes evaluated were cardiogenic shock (ICD-9 diagnosis code 785.51) and cardiac arrest (ICD-9 diagnosis code 427.5).
Invasive management of MI was defined as any in-hospital coronary angiography, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG), as reported by ICD-9 and Clinical Classifications Software (CCS) procedure codes during inpatient hospitalization. Patients who did not undergo an invasive approach to MI were considered to have been managed conservatively.
Statistical analysis
Categorical variables were reported as percentages and compared by the χ2 tests. Continuous variables were reported as mean ± standard deviation (SD) and compared using the Student’s t-test. Multivariable logistic regression models were generated to estimate odds ratios (ORs) for MACCE and its individual endpoints, adjusted for age, sex, race/ethnicity, obesity, tobacco use, hypertension, hyperlipidaemia, diabetes mellitus, end stage renal disease, coronary artery disease (CAD), prior revascularization with either PCI or CABG, peripheral arterial disease, congestive heart failure, valvular heart disease, prior venous thromboembolism, chronic lung disease, malignancy, anaemia, alcohol abuse, elective/urgent hospitalization, and year of hospitalization. Sampling weights were applied to determine national incidence estimates when specified. Unweighted data were used in all other analyses. Statistical analyses were performed using STATA MP 15 (StataCorp, College Station, TX, USA) and SPSS 20 (IBM SPSS Statistics, Armonk, NY, USA). Statistical tests are two-sided and P-values <0.05 were considered to be statistically significant.
Results
Study population and baseline characteristics
A total of 17,853,194 hospitalizations for major non-cardiac surgery were identified, corresponding to an estimated 85 533 934 hospitalizations for surgery in the United States during this time period. Of these, 49 978 patients (0.28%) underwent solid organ transplant surgery, corresponding to 241 482 transplant surgeries nationally after applying sampling weights. The most common single organ transplant surgeries were renal (67.3%, n = 33 658; ∼162 768 surgeries nationally), liver (21.6%, n = 10 810; ∼52 105 surgeries nationally), lung (6.7%, n = 3, 354; ∼16 215 surgeries nationally), and other single organ transplantation of the pancreas, intestine, or spleen (0.6%, n = 415; ∼1418 surgeries nationally). Multiple organ transplantations were performed in 3.5% of cases (n = 1741; ∼8401 surgeries nationally), of which 99.4% were double-organ transplants. Among these, 50.4% were renal transplantation with pancreas, intestine, or spleen transplantation, 43.8% were liver and renal transplantation, and 4.1% were transplantation of the liver and pancreas, intestine, or spleen. Baseline characteristics of patients undergoing transplant surgery are shown in Table 1. Overall, the mean age of transplant recipients was 51 years and 62% of transplant recipients were men.
Table 1.
Baseline characteristics of patients undergoing non-cardiac surgery stratified by transplant surgery
| Non-transplant surgery | Transplant surgery | P-value | |
|---|---|---|---|
| (n = 17 803 216) | (n = 49 978) | ||
| Age | 53.7 ± 19.6 | 51.2 ± 13.1 | <0.001 |
| Female sex | 11 519 908 (64.8%) | 19165 (38.4%) | <0.001 |
| Race | <0.001 | ||
| White Non-Hispanic | 10 562 368 (59.3%) | 25250 (50.5%) | |
| Black Non-Hispanic | 1 711 287 (9.6%) | 8039 (16.1%) | |
| Hispanic | 1 647 881 (9.3%) | 5839 (11.7%) | |
| Other | 887 856 (5%) | 3749 (7.5%) | |
| Unknown | 2 993 824 (16.8%) | 7101 (14.2%) | |
| Obesity | 1 917 029 (10.8%) | 4023 (8%) | <0.001 |
| Tobacco use | 3 231 811 (18.2%) | 8166 (16.3%) | <0.001 |
| Obstructive sleep apnoea | 538 767 (3%) | 1983 (4%) | <0.001 |
| Hypertension | 7 264 577 (40.8%) | 37 753 (75.5%) | <0.001 |
| Hyperlipidaemia | 3 525 923 (19.8%) | 11 329 (22.7%) | <0.001 |
| Diabetes mellitus | 2 960 865 (16.6%) | 16 441 (32.9%) | <0.001 |
| Chronic kidney diseasea | 747 646 (6.7%) | 24 010 (71.5%) | <0.001 |
| Coronary artery disease | 2 081 534 (11.7%) | 7183 (14.4%) | <0.001 |
| Prior PCI | 437 680 (2.5%) | 1991 (4%) | <0.001 |
| Prior CABG | 539 453 (3%) | 1707 (3.4%) | <0.001 |
| Peripheral arterial disease | 837 148 (4.7%) | 1816 (3.6%) | <0.001 |
| Valvular heart disease | 536 624 (3%) | 1793 (3.6%) | <0.001 |
| Malignancy | 682 572 (3.8%) | 2623 (5.2%) | <0.001 |
| Anaemia | 2 485 905 (14%) | 19195 (38.4%) | <0.001 |
| History of heart failure | 785 027 (4.4%) | 2322 (4.6%) | 0.01 |
| Prior alcohol abuse | 332 694 (1.9%) | 2031 (4.1%) | <0.001 |
| Prior drug abuse | 254 794 (1.4%) | 718 (1.4%) | 0.92 |
| Elective admission for surgery | 10 182 369 (57.4%) | 22 978 (46.1%) | <0.001 |
Data available for years 2008–2014 only.
Demographics and clinical comorbidities varied by subtype of transplant surgery, as shown in Table 2. Patients undergoing liver and lung transplantation were older than patients undergoing renal transplantation. Liver transplant recipients were less likely to be women in comparison to recipients of other transplanted organs. Among recipients of all non-cardiac solid organ transplantations, relatively few patients had established CAD or peripheral artery disease, with the highest prevalence in patients undergoing renal transplantation.
Table 2.
Baseline characteristics of patients by transplant surgery subtype
| Renal transplant | Liver transplant | Lung transplant | Intestine, pancreas, or spleen transplant | Multi-organ transplant | |
|---|---|---|---|---|---|
| (n = 33 658) | (n = 10 810) | (n = 3354) | (n = 415) | (n = 1741) | |
| Age (years) (SD) | 50.2 ± 13.7 | 54.0 ± 10.2 | 54.8 ± 13.1 | 44.0 ± 11.9 | 47.6 ± 11.5 |
| Age ≥ 45 years | 22 410 (66.6%) | 9270 (85.8%) | 2699 (80.5%) | 200 (48.2%) | 1053 (60.5%) |
| Female sex | 13358 (39.7%) | 3582 (33.1%) | 1356 (40.4%) | 213 (51.3%) | 656 (37.7%) |
| Race | |||||
| White Non-Hispanic | 15422 (45.8%) | 6325 (58.5%) | 2276 (67.9%) | 276 (66.5%) | 951 (54.6%) |
| Black Non-Hispanic | 6818 (20.3%) | 727 (6.7%) | 220 (6.6%) | 35 (8.4%) | 239 (13.7%) |
| Hispanic | 4189 (12.4%) | 1279 (11.8%) | 165 (4.9%) | 21 (5.1%) | 185 (10.6%) |
| Other | 2664 (7.9%) | 864 (8%) | 118 (3.5%) | 20 (4.8%) | 83 (4.8%) |
| Unknown | 4565 (13.6%) | 1615 (14.9%) | 575 (17.1%) | 63 (15.2%) | 283 (16.3%) |
| Obesity | 3123 (9.3%) | 668 (6.2%) | 156 (4.7%) | ≤10 (1.9%) | 68 (3.9%) |
| Tobacco use | 5156 (15.3%) | 1823 (16.9%) | 952 (28.4%) | 60 (14.5%) | 175 (10.1%) |
| Obstructive sleep apnoea | 1510 (4.5%) | 209 (1.9%) | 236 (7%) | ≤10 (0.5%) | 26 (1.5%) |
| Hypertension | 31 525 (93.7%) | 3563 (33%) | 1146 (34.2%) | 211 (50.8%) | 1308 (75.1%) |
| Hyperlipidaemia | 9582 (28.5%) | 646 (6%) | 666 (19.9%) | 90 (21.7%) | 345 (19.8%) |
| Diabetes mellitus | 11843 (35.2%) | 2584 (23.9%) | 608 (18.1%) | 276 (66.5%) | 1130 (64.9%) |
| Coronary artery disease | 5750 (17.1%) | 643 (5.9%) | 520 (15.5%) | 39 (9.4%) | 231 (13.3%) |
| Prior PCI | 1619 (4.8%) | 166 (1.5%) | 137 (4.1%) | ≤10 (1%) | 65 (3.7%) |
| Prior CABG | 1523 (4.5%) | 86 (0.8%) | 47 (1.4%) | ≤10 (1.7%) | 44 (2.5%) |
| Peripheral arterial disease | 1513 (4.5%) | 144 (1.3%) | 48 (1.4%) | 36 (8.7%) | 75 (4.3%) |
| Valvular heart disease | 1298 (3.9%) | 309 (2.9%) | 142 (4.2%) | ≤10 (1.2%) | 39 (2.2%) |
| Malignancy | 151 (0.4%) | 2334 (21.6%) | 38 (1.1%) | 11 (2.7%) | 89 (5.1%) |
| Anaemia | 15 506 (46.1%) | 2221 (20.5%) | 732 (21.8%) | 90 (21.7%) | 646 (37.1%) |
| History of heart failure | 1726 (5.1%) | 303 (2.8%) | 211 (6.3%) | 15 (3.6%) | 67 (3.8%) |
| Prior alcohol abuse | 166 (0.5%) | 1691 (15.6%) | 36 (1.1%) | ≤10 (0.7%) | 135 (7.8%) |
| Prior drug abuse | 313 (0.9%) | 340 (3.1%) | 36 (1.1%) | ≤10 (1.4%) | 23 (1.3%) |
| Elective admission for surgery | 18 406 (54.8%) | 3020 (28%) | 844 (25.2%) | 150 (36.2%) | 558 (32.2%) |
Among the 17 803 216 hospitalizations for non-transplant, non-cardiac surgery, orthopaedic (30.6%), obstetrics and gynaecology (23.9%), general (19.9%), and vascular surgeries (7.4%) were the most common surgical subtypes (Supplementary material online, Table S2). Characteristics of patients undergoing non-transplant, non-cardiac surgery are shown in Table 1.
In-hospital outcomes
Major adverse cardiovascular and cerebrovascular events occurred in 1 539 hospitalizations for transplant surgery (3.1%), corresponding to an estimated 7438 perioperative events nationwide during the time period of the study. Recipients of solid organ transplantation were more likely to have a perioperative major cardiovascular complication during hospitalization for transplant surgery in comparison to patients hospitalized for non-transplant, non-cardiac surgery [3.1% (1539 hospitalizations with MACCE) vs. 2.0% (356 556 hospitalizations with MACCE), P < 0.001] in unadjusted analyses, and after adjustment for demographics and comorbidities [adjusted OR (aOR) 1.29, 95% confidence interval [CI] 1.22–1.36]. Major adverse cardiovascular and cerebrovascular events after transplant surgery were driven by increased perioperative mortality (1.7% vs. 1.1%, P < 0.001; aOR 1.15, 95% CI 1.07–1.23) and more frequent perioperative MI (1.2% vs. 0.6%, P < 0.001; aOR 2.26, 95% CI 2.09–2.46) but not ischaemic stroke (0.3% vs. 0.5%, P < 0.001; aOR 0.56, 95% CI 0.47–0.65) in comparison to non-transplant surgery. Cardiogenic shock (0.4% vs. 0.1%, P < 0.001; aOR 5.07, 95% CI 4.39–5.85) and cardiac arrest (0.8% vs. 0.2%, P < 0.001; aOR 1.79, 95% CI 1.61–1.98) were also more common in patients undergoing solid organ transplantation in comparison to non-transplant surgery.
Demographics and baseline characteristics of transplant recipients with and without perioperative MACCE are shown in Supplementary material online, Table S3. Transplant recipients with MACCE were older, more likely to be men, and more likely to have CAD and peripheral artery disease in comparison to patients without MACCE. In a multivariable model, older age, prior CAD, peripheral artery disease, heart failure, and valvular disease were associated with perioperative MACCE after transplant surgery (Supplementary material online, Table S4).
Among patients with MI during hospitalization for transplant surgery (n = 621; ∼3009 perioperative MI nationally), invasive management was performed in 19.8% of cases. Coronary revascularization was performed in 9.8% cases. In-hospital mortality was 7.3% in patients who underwent invasive management of MI and 10.8% in patients who underwent conservative management, with no difference in the odds of in-hospital mortality after multivariable adjustment (aOR 0.75, 95% CI 0.33–1.74).
Surgery-specific perioperative major adverse cardiovascular and cerebrovascular events
Major adverse cardiovascular and cerebrovascular events varied by transplant surgery type (Table 3). The frequency of MACCE in patients undergoing single-organ renal, liver, and lung transplantation was 1.7%, 5.6%, and 7.5%, respectively (P < 0.001). After adjustment for demographics and comorbidities, liver transplant (aOR 2.10, 95% CI 1.93–2.28), lung transplant (aOR 3.50, 95% CI 3.07–4.00), and intestinal, pancreatic, or splenic solid organ transplant surgeries (aOR 3.48, 95% CI 2.15–5.64) were associated with increased odds of MACCE in comparison to non-transplant surgery. Renal transplant surgery was not associated with statistically significant increase in MACCE, due to a lower odds of death (aOR 0.71, 95% CI 0.65–0.77) despite an increased odds of MI (aOR 2.13, 95% CI 1.92—2.34) in comparison to non-transplant surgery after multivariable adjustment. Adjusted odds of MACCE by transplant surgery type (vs. non-cardiac, non-transplant surgery) are shown in Figure 1.
Table 3.
Perioperative outcomes of transplant surgery by surgical subtype
| Renal transplant surgery | Liver transplant surgery | Lung transplant surgery | Intestine, pancreas, or spleen transplant surgery | Multi-organ transplant surgery | P-value | |
|---|---|---|---|---|---|---|
| (n = 33658) | (n = 10810) | (n = 3354) | (n = 415) | (n = 1741) | ||
| Primary outcomes | ||||||
| MACCE (death/MI/stroke) | 570 (1.7%) | 607 (5.6%) | 250 (7.5%) | 18 (4.3%) | 94 (5.4%) | <0.001 |
| Death | 155 (0.5%) | 458 (4.2%) | 163 (4.9%) | 14 (3.4%) | 68 (3.9%) | <0.001 |
| Myocardial infarction | 414 (1.2%) | 142 (1.3%) | 39 (1.2%) | ≤10 (1.2%) | 21 (1.2%) | 0.953 |
| STEMI | 64 (0.2%) | 40 (0.4%) | 15 (0.4%) | ≤10 (0.2%) | ≤10 (0.2%) | 0.002 |
| NSTEMI | 350 (1%) | 102 (0.9%) | 24 (0.7%) | ≤10 (1%) | 18 (1%) | 0.454 |
| Acute ischaemic stroke | 36 (0.1%) | 49 (0.5%) | 58 (1.7%) | 0 (0%) | 13 (0.7%) | <0.001 |
| Secondary outcomes | ||||||
| Cardiogenic shock | 42 (0.1%) | 55 (0.5%) | 105 (3.1%) | 0 (0%) | ≤10 (0.4%) | <0.001 |
| Cardiac arrest | 137 (0.4%) | 180 (1.7%) | 64 (1.9%) | ≤10 (1%) | 15 (0.9%) | <0.001 |
Figure 1.
Adjusted odds of perioperative major adverse cardiovascular events (MACCE) by transplant surgery type in comparison to non-transplant surgery.
The management of perioperative MI also varied by transplant surgery type. Invasive management of MI was performed in 28.2% of lung transplant recipients, 21.7% of renal transplant recipients, and 14.8% of MI associated with liver transplantation. Revascularization in the setting of MI was performed in 12.3%, 5.6%, and 5.1% of renal, liver, and lung transplant recipients, respectively. Invasive management of acute MI (AMI) was not associated with lower mortality in any subgroups by transplant surgery type.
Discussion
In a large national cohort of adults undergoing solid organ transplant surgery, perioperative MACCE occurred among 3.1% of surgical hospitalizations. Patients undergoing transplant surgery had an increased incidence of MACCE driven by excess perioperative MI and death in comparison to patients undergoing non-transplant surgery. Risks of MACCE were greatest among patients undergoing liver transplant, lung transplant, and transplantation of the intestines, spleen or pancreas, but were not increased among renal transplant recipients when compared with patients undergoing non-transplant surgery. All transplant surgeries were associated with increased odds of perioperative MI in comparison to non-transplant surgeries.11 The perioperative MACCE associated with transplant surgery may reflect the burden of underlying cardiovascular comorbidities in this population, the severity of acute illness among transplant candidates, and the sequelae of long, complex surgeries that precipitate fluid shifts, anaemia, tachycardia, and haemodynamic instability.12
This is the first national analysis of perioperative outcomes of major solid organ transplant surgery. Prior studies include data from single centres or large registries but were specific to a single organ transplant type. In a single-centre study of 403 patients undergoing liver transplantation between 2001 and 2005, the composite of post-operative death or MI occurred in 12% of patients at 30 days. A history of CAD, stroke, sepsis, and echocardiographic parameters were associated with adverse perioperative cardiac outcomes, whereas use of perioperative β-blockers was significantly protective.6 Among patients undergoing renal transplantation identified from the United States Renal Data System, MI occurred in 4.3% at 6 months post-transplantation and was associated with older age, male sex, dyslipidaemia, diabetes mellitus, angina history, peripheral vascular disease, cardiac arrhythmias, and pre-transplantation AMI.2 There are few data on cardiovascular outcomes after lung transplantation.
Although transplant surgery is associated with a high frequency of perioperative cardiovascular events, the risk of mortality without transplantation still strongly favours transplantation despite these increased surgical risks. Unfortunately, optimal pre-operative cardiovascular evaluation and management of transplant candidates is uncertain. Due to limited availability of donor organs, the timing of transplantation surgery can be difficult to predict, and therefore, pre-operative cardiovascular risk stratification must consider both short- and long-term outcomes. In addition, patients awaiting transplant surgery frequently have comorbidities that complicate the standard management of cardiovascular disease. Current clinical practice guidelines for pre-operative cardiovascular evaluation prior to renal and liver transplantation surgery recognize these unique considerations and provide a limited set of surgery-specific recommendations to guide the care of these vulnerable patients.
According to the most recent American Heart Association Scientific Statement, published in 2012, all renal transplantation candidates should undergo a thorough examination and 12-lead electrocardiogram.3 Non-invasive stress testing should be considered in patients with multiple (≥3) CAD risk factors, and pre-operative cardiac troponin I or troponin T may be used as an additional prognostic marker. Perioperative aspirin, statin, and continuation of beta-blockers are reasonable to reduce post-operative cardiovascular risks. Routine cardiac catheterization prior to planned renal transplantation remains controversial. In patients who do have multi-vessel CAD, coronary revascularization may be considered, but routine prophylactic revascularization should not be performed without ischaemic symptoms or the potential to prolong survival.3 Current guidelines provide few recommendations for patients with end stage liver disease awaiting transplantation. Non-invasive stress testing and resting echocardiography may be considered, and non-selective beta-blockers are reasonable in patients with oesophageal varices.3 Clinical practice guidelines do not adequately address the optimal cardiovascular management of patients who require lung transplantation.13–15 European guidelines specific for the perioperative management of transplant recipients are limited and provide little additional insight; a comparison between the United States and European guideline recommendations are shown in Supplementary material online, Table S4.16,17 As a consequence, there may be considerable heterogeneity in perioperative management of patients undergoing transplantation.18–20
In the present analysis, we identify differential risks associated with each subtype of organ transplantation, with a greater risk of lung and liver transplantation than renal transplantation. There are a number of factors that potentially contribute to this observation. First, due to renal replacement therapy, renal transplantations are largely performed on an elective basis, and there is a lower threshold to defer surgery until a patient is medically optimized. Second, technical aspects of surgery and case complexity may also contribute to increased perioperative risks of liver and lung transplant surgery. Bleeding risks associated with liver disease may limit the use of antithrombotic therapies and contribute to cardiovascular risks. In lung transplantation, surgery is typically urgent or emergent, and profound hypoxia, right heart failure, and the requirement for cardiopulmonary bypass, may be associated with adverse cardiovascular outcomes. Based on this differential risk, the extent of the pre-operative cardiovascular evaluation should be in proportion to the inherent cardiovascular risk of the transplant candidate and the surgery-specific likelihood of adverse events in the perioperative period.
Study limitations
There are a few limitations of the present analysis. First, diagnosis codes recorded in the NIS are subject to reporting bias and/or errors in coding. Given sensitivity regarding operative complications of transplant surgery, diagnoses of perioperative MI may be under-reported. Myocardial injury after non-cardiac surgery, a post-operative finding strongly associated with morbidity and mortality even in the absence of AMI, does not have an assigned ICD-9 diagnosis code therefore could not be ascertained. Since many patients with perioperative MI are asymptomatic and routine biomarker collection after surgery is not recommended, MI may be missed entirely in some cases.21 Results of laboratory testing were not available from this administrative dataset. Importantly, transplant surgery recipients may be more likely to have cardiac biomarkers measured for perioperative MI screening than patients undergoing non-transplant surgery, and this surveillance bias may contribute to the higher incidence of perioperative MI reported in transplant surgery. Second, the results of cardiovascular imaging, including results of echocardiography and coronary angiography, were not recorded in the NIS. Third, in-hospital use of antithrombotic agents, statins, beta-blockers, and other medical therapies could not be determined. Fourth, the sequence of non-cardiac surgery preceding non-fatal cardiovascular complications cannot be definitively established in this large cohort. However, high-risk non-cardiac surgery is contraindicated early after stroke or AMI, and patients presenting with MACCE would be unlikely to undergo non-cardiac solid organ transplantation during the same hospital admission. Fifth, all heart transplantations were excluded from analysis, even when performed in combination with other solid organ transplantation. Sixth, data were analysed as a simple random sample (i.e. without using weights) for many of the analyses. This may introduce empirical weighting that may not be reflective of the national population of patients undergoing transplant surgery. Seventh, adjusted analyses to account for the burden of associated medical comorbidities may not control for unmeasured covariates. Finally, long-term out-of-hospital post-operative outcomes were not available from this in-hospital administrative dataset.
Conclusions
To our knowledge, this is the largest analysis of the perioperative outcomes of non-cardiac transplant surgery in the United States. Transplant surgery is strongly associated with higher MACCE, driven by an increased risk of death and perioperative AMI when compared with non-transplant surgery. However, not all transplant surgeries impart similar perioperative risks. Among the most commonly performed solid organ transplant surgeries, lung and liver transplantation were associated with the greatest perioperative cardiovascular risk, while renal transplant surgery was not associated with statistically significant increase in MACCE in comparison to non-transplant surgery. Additional efforts to reduce perioperative MACCE associated with non-cardiac organ transplant surgery are necessary.
Funding
National Heart, Lung, and Blood Institute of the National Institutes of Health (5T32HL098129 to N.R.S.).
Conflict of interest: none declared.
Supplementary Material
References
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