Abstract
Objective
Data regarding management of lower-extremity malperfusion in the setting of type A aortic dissection are limited. This study aimed to compare acute type A aortic dissection with lower-extremity malperfusion outcomes in patients undergoing lower-extremity revascularization with no revascularization.
Methods
Consecutive patients undergoing acute type A aortic dissection surgery were identified from a prospectively maintained database. Perioperative variables were compared between patients with and without lower-extremity malperfusion. Factors associated with lower-extremity malperfusion, revascularization, and mortality were determined using univariable Cox regression and Firth's penalized likelihood modeling.
Results
From January 2007 to December 2021, 601 patients underwent proximal aortic repair for acute type A aortic dissection at a quaternary care center. Of these, 85 of 601 patients (14%) presented with lower-extremity malperfusion and were more often male (P = .02), had concomitant moderate or greater aortic insufficiency (P = .05), had lower ejection fraction (P = .004), had preoperative dialysis dependence (P = .01), and had additional cerebral, visceral, and renal malperfusion syndromes (P < .001). Kaplan–Meier estimated survival fared worse with lower-extremity malperfusion compared with no lower-extremity malperfusion at 1, 5, and 10 years (84% vs 77%, 74% vs 71%, 65% vs 52%, respectively, P = .03). In the lower-extremity malperfusion group, 15 of 85 patients (18%) underwent lower-extremity revascularization without significant differences in postoperative morbidity and mortality compared with patients not undergoing revascularization. Need for peripheral revascularization was associated with peripheral vascular disease (hazard ratio, 3.7 [1.0-14.0], P = .05) and pulse deficit (hazard ratio, 5.6 [1.3-24.0], P = .02) at presentation.
Conclusions
Patients presenting with type A aortic dissection and lower-extremity malperfusion have worse overall survival compared with those without lower-extremity malperfusion. However, not all patients with type A aortic dissection and lower-extremity malperfusion require revascularization.
Key Words: aortic dissection, aortic repair, limb ischemia, malperfusion syndrome, peripheral vascular disease, revascularization
Graphical abstract
Graphical abstract.
Survival in TAAD with and without lower-extremity malperfusion.
Central Message.
With careful selection, LEM often resolves after proximal repair of TAAD.
Perspective.
Presentation of LEM in TAAD increases mortality, but optimal management in this complex situation is not well established. We found LEM resolved for a majority of patients after proximal aortic repair and identified factors associated with the need for revascularization.
See Discussion on page 14.
Acute aortic dissection management and outcomes are significantly influenced by the extent and location of dissection. Acute type A aortic dissection (TAAD) is typically managed with emergency surgery with mortality outcomes ranging from 15% to 30%.1,2 Perioperative outcomes for TAAD are particularly worse in the setting of malperfusion syndromes, with mortality rates increasing up to 43%.3, 4, 5 Concomitant lower-extremity malperfusion (LEM) occurs in less than 20% to 30% of patients presenting with TAAD, but the presence of preoperative limb ischemia increases the risk of mortality up to 2-fold.1,5, 6, 7 Although LEM has been identified as an important determinant of mortality in TAAD repair, there are few data comparing outcomes and optimal management in this complex situation.
The purpose of this study was to identify key differences in baseline characteristics and perioperative outcomes for patients undergoing TAAD repair with and without concomitant LEM. The LEM group was further analyzed to identify variables associated with lower-extremity revascularization and mortality.
Materials and Methods
Study Design
The Institutional Review Board or equivalent ethics committee of the University of Pittsburgh Medical Center approved the study protocol and publication of data on January 30, 2018 (Institutional Review Board #18120143). The patients provided informed written consent for the publication of the study data. Consecutive patients who underwent proximal aortic repair for TAAD were extracted from a prospectively maintained database between January 2007 and December 2021. Adult patients (age >18 years) with type A dissections presenting within 14 days of symptoms and undergoing open repair were included. Type B aortic dissections were excluded. Traumatic or iatrogenic aortic and peripheral vascular injuries were excluded.
Data Collection
Baseline health characteristics, intraoperative details, and in-hospital postoperative outcomes were obtained from an institutional database. LEM was defined by clinical symptoms with or without radiologic findings. Clinical symptoms included lower-extremity pain, paralysis, loss of sensation, pallor, paresthesias, and pulse deficit. Radiographic findings consistent with LEM included an aortic dissection extending to the common iliac or external iliac arteries. Patients with concomitant LEM and TAAD were identified, and additional data for these patients were collected through electronic medical records. Preoperative computed tomography (CT) imaging was reviewed to determine aortic dissection and LEM characteristics. Patients undergoing limb-related revascularization were then identified for subanalysis. End points of reintervention, amputation, and mortality were extracted through retrospective review of electronic records. Reintervention and amputation outcomes were specifically reviewed up to 1 year after the index operation. Follow-up data were obtained from the clinical warehouse that contains all long-term survival data for patients undergoing cardiac and aortic surgery at the University of Pittsburgh Medical Center. If patients were noted to be deceased but with no confirmed date, they were excluded from mortality analysis (unknown death date, n = 1). For patients who did not develop the event of interest (death) before September 15, 2021, when the information was extracted, the last date we have their information for serves as the censoring date.
Operative Details
A central aortic repair first strategy was applied for all patients except in cases of a threatened limb where revascularization was performed concomitantly with the index proximal aortic repair. Patients who underwent lower-extremity revascularization presented most frequently with absent pulses or clinical symptoms of LEM such as pain, decreased lower-extremity sensation, and paresthesias with correlating radiologic findings of lumen narrowing or dissection extending to the common or external iliac artery. The sequence of concomitant treatment was determined by urgency and surgeon preference, with lower-extremity revascularization performed before central aortic repair in 8 patients and after central aortic repair in 7 patients. There were 2 endovascular stents and 13 open interventions that were femoral-femoral arterial crossover bypass grafts. All lower-extremity interventions were performed by the cardiac surgery team.
Data Analysis
Baseline characteristics are presented as frequency (percentage) for categorical variables and mean (standard deviation) or median (interquartile range) for continuous variables that are or are not normally distributed, respectively. The distribution of data was examined by Shapiro-Wilk test. For categorical variables, Pearson's chi-square test was used for categorical comparisons. For continuous variables, Student t test or Mann–Whitney U test was used for comparison of the mean and median, respectively.
For logistic regression or multivariable Cox regression analysis, covariates other than lower extremity from the baseline characteristics (Table 1) were included in the model using the method of stepwise selection with a threshold of inclusion at P less than .2. The assumption of proportional hazards was validated using Schoenfeld residuals. In general, for variables that are included in the regression models, missing variables (usually <5%) were replaced by the mean value (for a continuous variable) or the most frequent categories (for a categorical variable).
Table 1.
Comparison of preoperative variables between patients with type A aortic dissection with and without concurrent lower-extremity malperfusion
| Preoperative baseline variables | No LEM (n = 516) | LEM (n = 85) | P value |
|---|---|---|---|
| Age (y) | 61.7 ± 13.8 | 59.2 ± 11.1 | .11 |
| Female gender | 216 (41.86) | 24 (28.24) | .02 |
| White | 426 (82.56) | 67 (78.82) | .41 |
| Body mass index (kg/m2) | 30.0 ± 6.69 | 30.1 ± 6.72 | .94 |
| Hypertension | 397 (76.94) | 60 (70.59) | .20 |
| Diabetes mellitus | 56 (10.85) | 7 (8.24) | .47 |
| Chronic lung disease | 78 (15.12) | 8 (9.41) | .16 |
| Peripheral vascular disease | 174 (33.72) | 33 (38.82) | .36 |
| Atrial fibrillation | 55 (10.66) | 6 (7.06) | .31 |
| Coronary artery disease | 76 (14.73) | 10 (11.76) | .47 |
| Redo heart surgery | 65 (12.60) | 7 (8.24) | .25 |
| Aortic insufficiency moderate or greater | 208 (40.31) | 44 (51.76) | .05 |
| Ejection fraction | 55.8 ± 8.78 | 52.6 ± 13.0 | .004 |
| Tamponade, rupture, or shock | 158 (30.62) | 29 (34.12) | .52 |
| Dialysis dependent | 8 (1.55) | 5 (5.88) | .01 |
| Hematocrit | 38.3 ± 6.02 | 39.4 ± 6.56 | .18 |
| Creatinine level | 1.28 ± 1.01 | 1.44 ± 1.09 | .25 |
| Type of malperfusion syndrome | |||
| Cerebral | 53 (10.27) | 21 (24.71) | <.001 |
| Coronary | 37 (7.17) | 5 (5.88) | .67 |
| Visceral | 20 (3.88) | 15 (17.65) | <.001 |
| Renal | 14 (2.71) | 22 (25.88) | <.001 |
LEM, Lower-extremity malperfusion.
Long-term survival curves were plotted using Kaplan–Meier estimate. Differences in the survival curves were analyzed using log-rank testing. Statistical analysis was performed using SAS version 9.4 (SAS Institute Inc).
Supplementary propensity score–matched analyses were performed using greedy nearest neighbor caliper matching, with calipers of width setting at 0.2 of standard deviation. Covariate balance is assessed by the P value and standardized mean difference with a threshold setting at 0.25. Propensity score matching incorporated preoperative variables provided in Table E1. All statistical analyses were performed using SAS/STAT Version 15.2 (SAS Institute Inc). All tests were 2-sided with an alpha level of 0.05 designated to indicate statistical significance.
Results
There were 601 patients from January 2007 to December 2021 who underwent TAAD proximal aortic repair at a single tertiary care center; of these patients, 85 of 601 (14%) presented with concomitant LEM. All 15 patients undergoing revascularization had clinical evidence of malperfusion such as pain, decreased lower-extremity sensation, paresthesias, or pulse deficit with or without radiographic evidence. Radiographic evidence of malperfusion was present in 10 of 15 patients undergoing revascularization. Preoperative, intraoperative, and postoperative outcome comparisons between patients with and without LEM are presented in Tables 1 and 2. Propensity-matched comparison based on preoperative characteristics is described in Tables E1 and E2. Kaplan–Meier estimated overall survival fared worse in patients with LEM compared with patients without LEM at 1, 5, and 10 years (84% vs 77%, 74% vs 71%, 65% vs 52%, respectively, P = .03) (Figure 1). For the entire cohort, LEM was not independently associated with increased mortality at 1 year (hazard ratio [HR], 1.42, confidence interval [CI], 0.84-2.40, P = .19) (Table E3).
Table 2.
Comparison of intraoperative and postoperative outcomes between patients with type A aortic dissection with and without concurrent lower-extremity malperfusion
| Intraoperative variable | No LEM (n = 516) | LEM (n = 85) | P value |
|---|---|---|---|
| Cannulation strategy | .301 | ||
| Aortic | 426 (82.56) | 64 (75.29) | |
| Subclavian | 45 (8.72) | 9 (10.59) | |
| Femoral | 25 (4.84) | 8 (9.41) | |
| Distal aorta | |||
| Hemiarch replacement | 333 (64.53) | 40 (47.06) | .002 |
| Total arch replacement | 168 (32.56) | 43 (50.59) | .001 |
| Conventional elephant trunk | 29 (5.62) | 10 (11.76) | .033 |
| Frozen elephant trunk | 47 (9.11) | 18 (21.18) | <.001 |
| Cardiopulmonary bypass time (min) | 199 ± 73.7 | 230 ± 69.8 | <.001 |
| Ischemic time (min) | 135 ± 61.0 | 159 ± 60.9 | .001 |
| Antegrade cerebral perfusion time (min), median (IQR) | 0.0 (0.0-25.0) | 15.0 (0.0-37.0) | .004 |
| Retrograde cerebral perfusion time (min), median (IQR) | 19.0 (0.0-27.0) | 20.0 (0.0-27.0) | .886 |
| Low body HCA time | 29.8 ± 14.9 | 32.9 ± 13.6 | .140 |
| Lowest core temperature | 22.4 ± 4.47 | 20.7 ± 2.10 | .003 |
| RBC transfusion | 203 (39.34) | 49 (57.65) | .002 |
| Total procedure time (h) | 5.16 ± 2.07 | 6.07 ± 2.37 | <.001 |
| Proximal reconstruction | |||
| Aortic valve resuspension | 311 (60.3) | 48 (56.5) | .508 |
| Aortic valve replacement | 32 (6.2) | 5 (5.9) | 1.00 |
| Valve-sparing root replacement | 104 (20.2) | 18 (21.2) | .828 |
| Complete aortic root replacement | 96 (18.6) | 15 (17.7) | .833 |
| Mechanical valve implant | 39 (7.6) | 6 (7.1) | 1.00 |
| Bioprosthetic valve implant | 55 (10.7) | 9 (10.6) | .984 |
| Postoperative outcome variables | |||
| In-hospital mortality | 53 (10.3) | 16 (18.8) | .02 |
| Total postoperative length of stay (d), median (IQR) | 8 (6-13) | 10.6 (6-18) | .12 |
| Follow-up time (y), median (IQR) | 4.6 (1.7-7.8) | 4.6 (1.2-7.8) | .59 |
| Mechanical ventilation time (h), median (IQR) | 11.3 (5.9-27.4) | 12.9 (6.0-52.0) | .097 |
| Lower-extremity fasciotomy | 1 (1.43) | 4 (26.67) | .003 |
| New-onset cerebrovascular accident | 19 (3.7) | 7 (8.2) | .06 |
| New-onset atrial fibrillation | 205 (39.7) | 39 (45.9) | .28 |
| Reexploration for bleeding | 49 (9.5) | 5 (5.9) | .28 |
| New-onset renal failure requiring hemodialysis | 46 (8.9) | 22 (25.9) | <.001 |
| Red blood cell transfusion | 197 (38.2) | 49 (57.7) | <.001 |
LEM, Lower-extremity malperfusion; IQR, interquartile range; HCA, hypothermic circulatory arrest; RBC, red blood cell.
Figure 1.
Survival in patients with TAAD presenting with concomitant LEM compared with no LEM.
Within the LEM group, 18% of patients (15/85) underwent lower-extremity revascularization. All revascularization procedures were completed at the time of initial aortic repair, with 8 of 15 cases receiving limb revascularization first and 7 of 15 cases receiving revascularization after proximal aortic repair. Two patients underwent endovascular stent repair, and 13 of 15 patients underwent open revascularization with femoral-femoral bypass.
The patients undergoing revascularization more often had underlying peripheral vascular disease (PVD) (P = .004) and associated pulse deficit (P = .01) at presentation (Table 3). Patients presenting with shock/tamponade were less likely to undergo revascularization. Adjusted odds ratios (ORs) based on the variables with P less than .2 on univariate analysis showed an increased likelihood of lower-extremity revascularization was associated with a pulse deficit (OR, 5.61, 95% CI, 0.99-24.04, P = .02), redo heart surgery (OR, 8.38, 95% CI, 1.02-68.90, P = .05), and PVD (OR, 3.73, 95% CI, 0.99-14.03, P = .05) (Table E5).
Table 3.
Contingency table evaluating the association of lower-extremity revascularization to clinical variables
| Variables | Frequency of lower-extremity revascularization | P value |
|---|---|---|
| Gender | .54 | |
| Male | 12/61 (19.7) | |
| Female | 3/24 (12.5) | |
| Race | .73 | |
| White | 11/67 (16.4) | |
| Other | 4/18 (22.2) | |
| Hypertension | .54 | |
| No | 3/25 (12.0) | |
| Yes | 12/60 (20.0) | |
| Diabetes mellitus | .60 | |
| No | 13/78 (16.7) | |
| Yes | 2/7 (28.6) | |
| Chronic lung disease | .14 | |
| No | 12/77 (15.6) | |
| Yes | 3/8 (37.5) | |
| Peripheral vascular disease | .004 | |
| No | 4/52 (7.7) | |
| Yes | 11/33 (33.3) | |
| Atrial fibrillation | .59 | |
| No | 15/79 (19.0) | |
| Yes | 0/6 (0.00) | |
| Coronary artery disease | .37 | |
| No | 12/75 (16.0) | |
| Yes | 3/10 (30.0) | |
| Redo heart surgery | .10 | |
| No | 12/78 (15.4) | |
| Yes | 3/7 (42.9) | |
| Aortic insufficiency moderate or greater | .78 | |
| No | 8/41 (19.5) | |
| Yes | 7/44 (15.9) | |
| Tamponade, rupture, or shock | .02 | |
| No | 14/56 (25.0) | |
| Yes | 1/29 (3.5) | |
| Current dialysis | .58 | |
| No | 15/80 (18.8) | |
| Yes | 0/5 (0.0) | |
| Cerebral malperfusion | .34 | |
| No | 13/64 (20.3) | |
| Yes | 2/21 (9.5) | |
| Coronary malperfusion | .58 | |
| No | 15/80 (18.8) | |
| Yes | 0/5 (0.0) | |
| Visceral malperfusion | 1.00 | |
| No | 13/70 (18.6) | |
| Yes | 2/15 (13.3) | |
| Renal malperfusion | 1.00 | |
| No | 11/63 (17.5) | |
| Yes | 4/22 (18.2) | |
| Previous lower-extremity intervention | .58 | |
| No | 15/80 (18.8) | |
| Yes | 0/5 (0.0) | |
| Pulse deficit | .01 | |
| No | 6/60 (10.0) | |
| Yes | 9/25 (36.0) | |
| Limb affected in LEM | .75 | |
| Left | 7/23 (30.4) | |
| Right | 5/24 (20.8) | |
| Both | 2/8 (25.0) |
LEM, Lower-extremity malperfusion.
There were no significant differences in postoperative outcomes of in-hospital mortality and morbidity between patients with LEM undergoing revascularization and no revascularization except for a higher rate of lower-extremity fasciotomy after revascularization (P = .003). Of the 22 patients in the LEM group with new-onset renal failure requiring hemodialysis, 13 patients had recovery of renal function and 9 patients had evidence on long-term renal failure at the time of discharge. In the LEM group, there were 16 in-hospital mortalities. Of these, 5 of 16 were aortic related, 9 of 16 were related to shock/multiorgan system failure, and 2 of 16 were secondary to respiratory failure. Overall, 4 of 601 patients underwent reintervention on the descending aorta and 6 of 601 patients required reintervention on the proximal aorta. Three patients required reintervention for both proximal and descending aortas.
Comparison of preoperative CT imaging showed partial/complete thrombosis of the iliac artery (P = .03) and partial thrombosis of the false lumen (P = .05) more frequently in the revascularization group (Table 4). There were no lower-extremity amputations in the cohort. Estimated Kaplan–Meier survival was worse overall for patients with LEM undergoing revascularization compared with patients not undergoing revascularization (P = .008) (Figure 2). Univariable analyses are provided in Tables E4 and E6. In the LEM group, univariate factors associated with mortality included White race, hypertension, diabetes mellitus, and atrial fibrillation. After adjustment, the variables White race (HR, 0.37, 95% CI, 0.2-0.8, P = .02) and atrial fibrillation (HR, 5.0, 95% CI, 1.65-14.88, P = .004) remained significant (Table 5).
Table 4.
Imaging characteristics of type A aortic dissections presenting with lower-extremity malperfusion compared between those undergoing no revascularization and those undergoing revascularization
| Variable | No lower-extremity revascularization (n = 70) | Lower-extremity revascularization (n = 15) | P value |
|---|---|---|---|
| Primary tear location | .40 | ||
| Noncoronary sinus | 14 (20.00) | 0 (0.00) | |
| Left coronary sinus | 2 (2.86) | 0 (0.00) | |
| Right coronary sinus | 2 (2.86) | 1 (6.67) | |
| Sinotubular junction | 15 (21.43) | 2 (13.33) | |
| Ascending aorta | 27 (38.57) | 8 (53.33) | |
| Aortic arch | 8 (11.43) | 3 (20.00) | |
| Secondary arch tear | 17 (24.29) | 4 (26.67) | .85 |
| Left main coronary artery | 0 (0.00) | 0 (0.00) | 1.00 |
| Right main coronary artery | 2 (2.86) | 0 (0.00) | 1.00 |
| Concomitant coronary artery bypass graft | 6 (8.57) | 3 (20.00) | .19 |
| Extent of residual type B dissection | .39 | ||
| 0 | 24 (48.0) | 6 (46.15) | |
| 1 (Descending thoracic aorta) | 2 (4.0) | 1 (7.69) | |
| 2 (Mesenteric) | 0 (0.0) | 1 (7.69) | |
| 3 (Infrarenal) | 2 (4.0) | 0 (0.0) | |
| 4 (Iliac) | 22 (44.0) | 5 (38.5) | |
| Missing | 20 | 2 | |
| Partial/complete thrombosis of iliac artery (missing) | 19 (35.2) 16 | 6 (75.0) 7 | .03 |
| False lumen diameter greater than true lumen (missing) | 46 (85.2) 16 | 8 (100) 7 | .24 |
| True lumen collapsed at level of paravisceral aorta (missing) | 5 (9.6) 18 | 2 (25.0) 7 | .23 |
| Complete true lumen collapse/compression (missing) | 6 (11.5) 18 | 7 (12.5) 7 | 1.00 |
| False lumen patent (missing) | 46 (85.2) 16 | 8 (100) 7 | .58 |
| False lumen partially thrombosed (missing) | 17 (30.9) 15 | 6 (75.0) 7 | .04 |
| Pericardial effusion | 6 (8.6) | 2 (13.3) | .63 |
Figure 2.
Survival in patients with TAAD with LEM undergoing lower-extremity revascularization compared with no revascularization.
Table 5.
Adjusted hazard ratio of mortality (based on the univariate model P < .2) in patients with type A aortic dissection and lower-extremity malperfusion
| Variables | Hazard ratio (95% CI) | P value |
|---|---|---|
| White | 0.37 (0.16-0.83) | .02 |
| Hypertension | 0.40 (0.82-7.01) | .11 |
| Diabetes mellitus | 1.34 (0.49-3.69) | .57 |
| Chronic lung disease | 1.63 (0.56-4.75) | .37 |
| Malperfusion syndrome: coronary | 2.37 (0.75-7.52) | .14 |
| Aortic insufficiency moderate or greater | 0.54 (0.25-1.15) | .11 |
| Atrial fibrillation | 4.96 (1.65-14.88) | .004 |
Harrell C statistic 0.751. CI, Confidence interval.
Discussion
Malperfusion syndromes in the setting of acute TAAD complicate clinical decision making because adverse outcomes occur more frequently in the setting of end-organ malperfusion. Fortunately, appropriate preoperative and intraoperative management of malperfusion syndromes can reduce mortality outcomes to 4% to 13%.3 This study focuses specifically on peripheral malperfusion in TAAD and is one of the few to analyze outcomes in these patients undergoing revascularization versus conservative management (Figure 3).
Figure 3.
Graphical abstract.
Consistent with previous studies, our study found 14% of patients (85/601) with TAAD presented with LEM.8, 9, 10 A majority of the patients with LEM in our study were managed with proximal aortic repair, and 18% (15/85) underwent lower-extremity revascularization. Others have reported a 0% to 3% amputation rate in this patient population.9,11,12 In our cohort, no patients with LEM required amputation regardless of revascularization status.
Patient Demographics and Baseline Characteristics
Preoperative variables more commonly found in the LEM group included male gender, aortic valve insufficiency, depressed ejection fraction, baseline dialysis dependence, and concomitant malperfusion syndromes compared with patients with no LEM. These results are similar to those of Charlton-Ouw and colleagues,13 who also found baseline characteristics of male gender, aortic valve insufficiency, renal dysfunction, and other malperfusion syndromes more often associated with ischemic limb on presentation. Unlike other studies that identify PVD to be associated with LEM, our study did not find the incidence of PVD was significantly different between groups.1 However, when LEM was present, PVD was found to be associated with revascularization.
After propensity matching based on preoperative patient characteristics, differences in early postoperative outcomes were no longer significant. Results indicate that underlying patient factors may drive outcomes of TAAD repair irrespective of malperfusion.
In-hospital Morbidity and Mortality
Malperfusion syndromes can result in prolonged end-organ ischemia, setting off an inflammatory cascade that influences operative risk and postoperative healing.12,14 Peripheral malperfusion has been extensively identified as a risk factor of mortality,15,16 but Narayan and colleagues17 go further to argue that the presence of malperfusion impacts mortality more than even the timing of intervention from symptom onset.
Our results demonstrate that patients with LEM more often required complex aortic repair with longer cardiopulmonary bypass and overall procedure times, and were more likely to be dependent on the ventilator, dialysis, and blood transfusions compared with patients without LEM. These perioperative factors further contribute to the capillary leak phenomenon and worsening shock, which likely contributed to the higher in-hospital mortality in the LEM group compared with no LEM. In the LEM group, undergoing revascularization did not influence in-hospital mortality. After adjustment, variables of White race and atrial fibrillation were significantly associated with increased mortality risk in the LEM group.
Long-term Survival
Geirsson and colleagues18 demonstrated worse long-term survival for patients with malperfusion syndromes compared with patients without at 1, 5, and 10 years (68% vs 83% at 1 year, 54% vs 66% at 5 years, and 43% vs 46% at 10 years, respectively). When specifically analyzing survival in patients with TAAD with and without LEM, we also found survival was significantly worse in the LEM group (78% vs 84% at 1 year, 71% vs 74% at 5 years, and 52% vs 65% at 10 years, respectively) (Figure 1).
Similar to results published by Beck and colleagues,8 within the LEM group, patients undergoing lower-extremity revascularization also had overall decreased late survival compared with patients not undergoing revascularization. This warrants further investigation because the perioperative outcomes were largely similar between these patients.
Role of Revascularization
When considering aortic dissections, some advocate aortic first intervention to restore flow in the true lumen to treat peripheral perfusion, whereas others prefer limb revascularization first.11,19,20 Plotkin and colleagues11 compared these 2 strategies and found the aortic first intervention led to successful LEM resolution in 72% of patients (26/36), whereas limb first revascularization was successful in 50% (3/6). Charlton-Ouw and colleagues13 found up to one-third of patients with LEM may require revascularization after the proximal aortic repair. However, these studies included both type A and type B aortic dissections, whereas our study focused on acute TAADs for which aortic repair was undertaken in an urgent fashion.
Norton and colleagues20 recently reported their results of revascularization first approach in 25 patients presenting with LEM in TAAD. Of the 25, 16 patients underwent subsequent delayed open aortic repair, 3 were discharged without repair, and 6 patients died before undergoing proximal aortic repair. Postoperative outcomes were not significantly different in patients undergoing delayed aortic repair compared with patients without LEM, but the 24% (6/25) mortality rate in this subset raises concern regarding this approach.
Our results are in agreement with previous studies that have demonstrated proximal aortic repair successfully resolves LEM in the majority of cases.8,9,11,21 In our cohort, all patients were treated with an aortic first approach with concomitant limb revascularization when there was clinical evidence of a threatened limb. Surgeon preference and assessment of patient factors drove decision making of treatment sequence for limb revascularization, with approximately half of the patients treated with the aortic repair first and the other half undergoing limb revascularization before aortic repair. No patients required reintervention or return to the operating room for further revascularization procedures or amputations after the index case. In-hospital mortality did not differ between patients with LEM undergoing revascularization and patients with no revascularization. Our results support that a patient-specific approach, focusing on the presenting patient factors, may aid in identification of patients who benefit most from revascularization at the time of initial intervention without impacting early survival.
Factors Associated With Revascularization
There are few studies comparing patients with LEM and TAAD undergoing revascularization with no revascularization. In one study, Beck and colleagues8 did not find differences in demographics or comorbidities between patients with TAAD requiring revascularization. However, in our study, consistent with Charlton-Ouw and colleagues,13 we found peripheral arterial disease and pulse deficit were associated with the need for revascularization.
A patient presenting with tamponade or shock was less likely to undergo peripheral revascularization. Given the overall higher acuity and tenuous condition of the patient in this circumstance, it is not unexpected that LEM was observed rather than intervened upon.
Anatomic and dissection characteristics based on CT imaging are depicted in Table 4. Beck and colleagues8 have also analyzed imaging characteristics in patients with TAAD and LEM. In contrast to Beck and colleagues' results, the extent of the dissection did not influence the need for revascularization in our study. Iliac artery thrombosis was similarly more common in the revascularization group. A new finding in our study was that patients with false lumen thrombosis also were more likely to require revascularization.
Fattouch and colleagues22 found a patent false lumen to be associated with the need for re-treatment and late mortality after proximal TAAD repair. Our study did not find false lumen patency to be associated with revascularization need at the time of proximal aortic repair. However, this study was limited by the number of patients undergoing revascularizations, and available CT imaging data such that association of imaging factors and mortality could not be reliably attained.
The focus of this study was on proximal aortic repair with or without peripheral revascularization. However, alternative options such as antegrade stent deployment in the descending aorta at the time of proximal aortic repair have been demonstrated by Preventza and colleagues,23,24 with less short-term operative mortality and improved false lumen remodeling and overall survival at midterm follow-up. Although the optimal approach warrants further investigation, the clinical strategy should be tailored to the patient's presentation.25
Concomitant Malperfusion Syndromes
Concomitant mesenteric, coronary, and cerebral malperfusion can result in more lethal implications compared with lower-extremity ischemia, yet malperfusion syndromes are often used as a composite variable to calculate risk in TAAD outcome studies.5,23,24,26 Jaffar-Karballai and colleagues10 compared multiple studies on this topic, finding that limb malperfusion had a higher incidence anywhere from 6% to 53%, but mortality in these patients ranged from 3% to 24%. Although mesenteric, coronary, and cerebral malperfusion syndromes were often associated with higher mortality rates of 20% to 75%. Charlton-Ouw and colleagues13 reported patients requiring peripheral limb revascularization were more likely to have associated mesenteric ischemia and overall worse 10-year survival (22% vs 59%, P < .001).
In this study, renal, visceral, and cerebral malperfusion syndromes were more often present in the LEM group (P < .001). Concomitant malperfusion syndrome was not independently associated with mortality. Specifically, we also did not find that any particular concomitant malperfusion syndrome was associated with the need for revascularization.
Study Limitations
A limitation of the study is its retrospective nature with inherent treatment and hospital center-specific bias. Comfort level among surgeons may have varied and influenced the decision to pursue lower-extremity revascularization at the time of proximal aortic repair. There was not adequate data to determine if timing from symptom onset to operative repair influenced outcomes. The low number of patients undergoing revascularization overall was a limitation to the type of statistical analyses that could be reliably performed.
It should be acknowledged that the study data are based on electronic medical record review and a single-center database. After the index operation, patient presentation to hospitals outside of our health system could have contributed to missing follow-up data points and limited study outcomes.
This study focused on imaging characteristics as determinants of revascularization. Additional factors that could determine Rutherford grade of limb ischemia or biochemical markers were not available for study but could have influenced revascularization decision. Components of variables measured by CT imaging were missing in up to 30% of patients (25/85). Patients with TAAD often were diagnosed elsewhere and transferred to our institution, and although imaging reports were available through electronic medical records, the CT scans were at times transferred on a disc without being uploaded to a permanent location. Thus, with approximately one-third of patients missing imaging data, the results should be interpreted cautiously and warrant further investigation.
Conclusions
LEM complicates TAAD presentation and management. Male gender, aortic insufficiency, low ejection fraction, and dialysis dependence were found more often in patients presenting with LEM compared with TAAD without LEM. These factors translated into a more complex intraoperative and postoperative hospital course, and worse survival compared with patients without LEM. Concomitant malperfusion syndromes were not associated with worse prognosis in this study.
Although LEM resolved for a majority of patients after proximal aortic repair, those who required revascularization were more likely to present with a pulse deficit and a history of PVD. Iliac artery and false lumen thrombosis were more often associated with the need for revascularization. There were no differences in postoperative morbidity and in-hospital mortality between patients undergoing revascularization versus no revascularization with 100% limb preservation.
Webcast
You can watch a Webcast of this AATS meeting presentation by going to: https://www.aats.org/resources/outcomes-of-lower-extremity-malperfusion-syndrome-in-patients-undergoing-proximal-type-a-aortic-dissection-repair.
Conflict of Interest Statement
I.S. receives institutional research support from Abbott, Artivion, Boston Scientific, Medtronic, and AtriCure, and consults for Medtronic Vascular. None of these are related to this manuscript. All other authors reported no conflicts of interest.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
Footnotes
Institutional Review Board #18120143.
Appendix E1
Table E1.
Demographic and clinical variables in those with or without lower-extremity malperfusion in propensity score–matched samples
| Variable | No LEM (n = 75) | LEM (n = 75) | Absolute standard median deviation | P value |
|---|---|---|---|---|
| Age (y) | 60.6 ± 14.8 | 60.5 ± 10.4 | 0.008 | .934 |
| Female | 22 (29.33) | 24 (32.00) | 0.058 | .723 |
| White | 57 (76.00) | 59 (78.67) | 0.064 | .697 |
| Body mass index (kg/m2) | 30.5 ± 7.79 | 30.1 ± 6.84 | 0.054 | .753 |
| Hypertension | 59 (78.67) | 52 (69.33) | 0.214 | .193 |
| Diabetes mellitus | 6 (8.00) | 6 (8.00) | 0 | 1.000 |
| Chronic lung disease | 8 (10.67) | 7 (9.33) | 0.045 | .786 |
| Peripheral vascular disease | 23 (30.67) | 30 (40.00) | 0.196 | .232 |
| Atrial fibrillation | 10 (13.33) | 6 (8.00) | 0.173 | .290 |
| Coronary artery disease | 13 (17.33) | 10 (13.33) | 0.111 | .497 |
| Redo heart surgery | 11 (14.67) | 7 (9.33) | 0.165 | .315 |
| Aortic insufficiency moderate or greater | 31 (41.33) | 39 (52.00) | 0.215 | .190 |
| Ejection fraction | 53.1 ± 10.3 | 52.6 ± 13.5 | 0.042 | .826 |
| Tamponade, rupture, or shock | 31 (41.33) | 26 (34.67) | 0.138 | .400 |
| Current dialysis | 6 (8.00) | 3 (4.00) | 0.169 | .302 |
| Preoperative hematocrit | 37.0 ± 6.60 | 39.2 ± 6.94 | 0.325 | .100 |
| Preoperative creatinine level | 1 (1-2) | 1 (1-1) | NA | .049 |
| Type of malperfusion syndrome | ||||
| Cerebral | 15 (20.00) | 17 (22.67) | 0.055 | .690 |
| Coronary | 5 (6.67) | 4 (5.33) | 0.056 | .731 |
| Visceral | 12 (16.00) | 8 (10.67) | 0.157 | .337 |
| Renal | 14 (18.67) | 12 (16.00) | 0.071 | .666 |
LEM, Lower-extremity malperfusion; NA, not available.
Table E2.
Postoperative outcomes compared with or without lower-extremity malperfusion in propensity score–matched sample
| Variable | No LEM (n = 75) | LEM (n = 75) | P value |
|---|---|---|---|
| In-hospital mortality | 9 (12.00) | 14 (18.67) | .26 |
| Total postoperative length of stay (d) | 15.9 ± 17.9 | 13.9 ± 13.6 | .43 |
| Follow-up time (y), median (IQR) | 3.74 (1.27-6.1) | 4.58 (1.18-7.7) | .62 |
| Mechanical ventilation time (h) | |||
| Mean ± SD | 56.2 ± 99.4 | 84.4 ± 192.0 | .28 |
| Median (IQR) | 12.35 (7.35-44.0) | 12.83 (5.77-38.1) | .10 |
| Postoperative pneumonia | 10 (13.33) | 9 (12.00) | .81 |
| New-onset cerebrovascular accident | 4 (5.33) | 7 (9.33) | .35 |
| Postoperative atrial fibrillation | 36 (48.00) | 33 (44.00) | .62 |
| Reexploration for excessive bleeding | 11 (14.67) | 5 (6.67) | .11 |
| New-onset renal failure requiring hemodialysis | 11 (14.67) | 16 (21.33) | .29 |
| Red blood cell transfusion | 33 (44.00) | 44 (58.67) | .07 |
LEM, Lower-extremity malperfusion; IQR, interquartile range; SD, standard deviation.
Table E3.
Multivariable Cox proportional-hazards regression model for 1-year survival in all patients undergoing type A aortic dissection repair
| Variable | Hazard ratio (95% CI) | P value |
|---|---|---|
| LEM | 1.42 (0.84-2.40) | .19 |
| Gender (female) | 1.48 (0.98-2.25) | .06 |
| Age (y) | 1.06 (1.04-1.08) | <.001 |
| Race, White | 0.45 (0.27-0.73) | .001 |
| Diabetes mellitus | 1.98 (1.17-3.33) | .01 |
| Ejection fraction | 0.98 (0.96-0.99) | .005 |
| Tamponade, rupture, or shock | 1.61 (1.08-2.41) | .02 |
| Dialysis | 2.68 (0.92-7.76) | .07 |
| Coronary malperfusion | 2.96 (1.66-5.27) | <.001 |
| Total arch repair | 3.39 (2.20-5.20) | <.001 |
| Coronary artery disease | 1.44 (0.87-2.39) | .16 |
CI, Confidence interval; LEM, lower-extremity malperfusion.
Table E4.
Univariable logistic regression for lower-extremity revascularization
| Variable | OR (95% CI) | P value |
|---|---|---|
| Age (y) | 0.98 (0.93-1.03) | .37 |
| Female | 0.65 (0.17-2.39) | .51 |
| White | 0.66 (0.19-2.31) | .51 |
| Body mass index (kg/m2) | 0.97 (0.88-1.06) | .46 |
| Hypertension | 1.66 (0.45-6.13) | .45 |
| Diabetes mellitus | 2.21 (0.40-12.12) | .36 |
| Chronic lung disease | 3.34 (0.71-15.66) | .13 |
| Peripheral vascular disease | 5.51 (1.64-18.53) | .006 |
| Atrial fibrillation | 0.32 (0.01-7.52) | .47 |
| Coronary artery disease | 2.37 (0.55-10.25) | .25 |
| Redo heart surgery | 4.14 (0.83-20.76) | .08 |
| Aortic insufficiency moderate or greater | 0.79 (0.26-2.37) | .67 |
| Ejection fraction | 0.98 (0.95-1.02) | .67 |
| Tamponade, rupture, or shock | 0.15 (0.03-0.91) | .04 |
| Current dialysis | 0.38 (0.02-9.62) | .56 |
| Malperfusion syndrome | ||
| Cerebral | 0.49 (0.11-2.14) | .34 |
| Coronary | 0.38 (0.02-9.62) | .34 |
| Visceral | 0.79 (0.17-3.59) | .76 |
| Renal | 1.11 (0.32-3.81) | .87 |
| Previous lower-extremity intervention | 0.38 (0.02-9.62) | .56 |
| Pulse deficit | 4.83 (1.52-15.33) | .008 |
| Limb affected in LEM | ||
| Left (ref) | 1 | |
| Right | 0.62 (0.17-2.29) | .47 |
| Both | 0.86 (0.14-5.02) | .85 |
OR, Odds ratio; CI, confidence interval; LEM, lower-extremity malperfusion.
Table E5.
Adjusted odds ratios of lower-extremity revascularization estimated by penalized maximum likelihood
| Variable | OR (95% CI) | P value |
|---|---|---|
| Chronic lung disease | 7.04 (0.91-54.73) | .062 |
| Peripheral vascular disease | 3.73 (0.99-14.03) | .052 |
| Paulse deficit | 5.61 (1.31-24.04) | .020 |
| Tamponade, rupture, or shock | 0.16 (0.02-1.14) | .067 |
| Redo heart surgery | 8.38 (1.02-68.90) | .048 |
C statistics 0.897. Variables selection: P < .2 based on univariate analysis. OR, Odds ratio; CI, confidence interval.
Table E6.
Univariable Cox regression for mortality in patients with type A aortic dissection and lower-extremity malperfusion
| Variable | HR (95% CI) | P value |
|---|---|---|
| Age (y) | 1.01 (0.97-1.04) | .77 |
| Female | 1.59 (0.77-3.29) | .21 |
| White | 0.35 (0.16-0.75) | .007 |
| Body mass index (kg/m2) | 1.02 (0.98-1.07) | .32 |
| Hypertension | 3.20 (1.17-8.75) | .02 |
| Diabetes mellitus | 2.42 (1.01-5.79) | .05 |
| Chronic lung disease | 2.23 (0.87-5.72) | .10 |
| Peripheral vascular disease | 1.08 (0.54-2.15) | .82 |
| Atrial fibrillation | 7.27 (2.67-19.78) | <.001 |
| Coronary artery disease | 1.54 (0.61-3.91) | .36 |
| Redo heart surgery | 1.38 (0.50-3.86) | .54 |
| Aortic insufficiency moderate or greater | 0.54 (0.27-1.07) | .08 |
| Ejection fraction | 0.99 (0.96-1.02) | .49 |
| Tamponade, rupture, or shock | 1.13 (0.54-2.35) | .75 |
| Current dialysis | 1.65 (0.44-6.19) | .46 |
| Malperfusion syndrome | ||
| Cerebral | 1.02 (0.46-2.26) | .96 |
| Coronary | 2.49 (0.90-6.09) | .08 |
| Visceral | 1.39 (0.61-3.18) | .43 |
| Renal | 0.96 (0.45-2.07) | .92 |
| Previous lower-extremity intervention | 0.93 (0.18-4.96) | .93 |
| Pulse deficit | 1.25 (0.61-2.54) | .54 |
| Limb affected in LEM | ||
| Left (ref) | 1 | |
| Right | 0.57 (0.20-1.62) | .29 |
| Both | 1.59 (0.52-4.87) | .41 |
HR, Hazard ratio; CI, confidence interval; LEM, lower-extremity malperfusion.
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