Surgical aortic valve replacement (S-AVR) after previous cardiac surgery is expected to be associated with a high rate of adverse events. The aim of this study was to estimate the rate and identify the determinants of postoperative stroke in these patients. This is a multicenter study including 741 patients who underwent S-AVR after previous cardiac surgery. Forty-eight patients (6.5%; after isolated AVR, 6.0%) suffered stroke and 10 of them died during the in-hospital stay (20.8%). At multivariate analysis, women (10.2% vs 4.4%, odds ratio [OR] 2.57, 95% confidence interval [CI] 1.36 to 4.86), emergency procedure (15.1% vs 4.8%, OR 2.63, 95% CI 1.12 to 5.78), perioperative use of intra-aortic balloon pump (22.9% vs 5.3%, OR 2.67, 95% CI 1.15 to 6.19), cardiopulmonary bypass time of >210 minutes (15.7% vs 5.0%, OR 2.31, 95% CI 1.13 to 4.71), blood products transfusion (9.3% vs 0.8%, OR 7.75, 95% CI 1.83 to 32.93), and reexploration for bleeding (24.0% vs 5.2%, OR 4.84, 95% CI 2.18 to 10.77) were independent predictors of postoperative stroke. These findings were confirmed by a regression model including CHA 2 DS 2 -VASc score of ≥2, which itself was predictive of stroke (8.2% vs 1.6%, OR 4.52, 95% CI 1.34 to 15.28). Survival at 3 years in patients with postoperative stroke was 51.9%, whereas it was 85.0% in control patients (adjusted analysis: relative risk 2.97 and 1.86 to 4.72, respectively). In conclusion, the risk of postoperative stroke after S-AVR in patients with previous cardiac surgery is high and has an impact on the immediate and late mortality. Excessive bleeding requiring blood transfusion and/or reexploration, prolonged cardiopulmonary bypass time, and use of intra-aortic balloon pump were associated with an extremely high rate of stroke.
Redo cardiac surgery can be technically demanding because of the difficulties to access to the heart in a scarred field, requires long operation times, and exposes the patients to the risk of iatrogenic injury to vascular and cardiac structures at reentry and of significant blood losses. Furthermore, underlying previous and current cardiac diseases may significantly contribute to adverse outcome. These factors may contribute to an increased risk of adverse postoperative events.
Stroke is one of the most important outcome end points after cardiac surgery. Complex surgery requiring prolonged cardiopulmonary bypass time and usually associated excessive bleeding may increase the risk of cerebrovascular events. The aim of this study is to assess the incidence and determinants of postoperative stroke and its impact on late survival in patients undergoing surgical aortic valve replacement (S-AVR) after previous cardiac surgery in a multicenter European current practice, involving “all-comers” to redo AVR at 7 different European institutions. In particular, we focused on the impact of perioperative risk factors such as blood transfusion and reexploration for bleeding on the occurrence of this severe complication.
Methods
This is an analysis of 741 consecutive patients who have been operated on from 2000 to 2013 in 7 centers in Italy, Germany, and Finland and contributing to the multicenter REdo Cardiac Operation Research Database. Baseline and operative characteristics of these patients are listed in Tables 1 and 2 . The inclusion criterion for this study was any S-AVR performed in patients with any history of previous cardiac surgery. We excluded from this analysis patients who underwent transcatheter aortic valve implantation or AVR using sutureless aortic valve prosthesis. Patients with acute endocarditis were not excluded from this study. Data on demographic variables, clinical characteristics, type of operation, and postoperative outcome were retrieved and each center conducted an active follow-up to determine patients’ life status. Herein, blood transfusion indicates any transfusion of red blood cells, platelets, and/or Octaplas/fresh frozen plasma. Reexploration was defined as any reintervention performed for excessive bleeding.
| Variable | Postoperative Stroke | Univariate Analysis p Value | |
|---|---|---|---|
| No (n = 693) | Yes (n = 48) | ||
| Age (yrs) | 66.8 ± 13.3 | 68.5 ± 11.5 | 0.407 |
| Women | 237 (34.2) | 27 (56) | 0.002 |
| Diabetes mellitus | 150 (21.6) | 12 (25) | 0.587 |
| Renal failure | 109 (15.7) | 9 (19) | 0.580 |
| Hypertension | 330 (47.7) | 26 (54) | 0.385 |
| Stroke | 69 (10) | 5 (10) | 0.918 |
| Pulmonary disease | 100 (14.4) | 7 (15) | 0.977 |
| Peripheral vascular disease | 64 (9.2) | 4 (8) | 1.000 |
| Left ventricular ejection fraction of ≤30% | 34 (4.9) | 7 (15) | 0.013 |
| Myocardial infarction | 80 (11.5) | 4 (8) | 0.497 |
| Pulmonary hypertension | 81 (11.7) | 10 (21) | 0.062 |
| Atrial or ventricular arrhythmia at admission (any type) | 136 (19.6) | 14 (29) | 0.112 |
| New York Heart Association class IV | 104 (15.1) | 11 (23) | 0.143 |
| Acute endocarditis | 140 (20.2) | 18 (38) | 0.005 |
| Emergency procedure | 36 (5.2) | 12 (19) | <0.0001 |
| Previous procedure | |||
| Coronary artery bypass grafting | 218 (31.5) | 12 (25) | 0.350 |
| Any valve surgery | 453 (65.4) | 36 (75) | 0.173 |
| Aortic valve surgery | 48 (6.9) | 1 (2) | 0.192 |
| CHA 2 DS 2 -VASc score of ≥2 | 501 (72.7) | 45 (94) | 0.001 |
| Additive EuroSCORE | 10.0 ± 3.3 | 11.5 ± 4.2 | 0.011 |
| Operative Variable | Postoperative Stroke | Univariate Analysis p Value | |
|---|---|---|---|
| No, n = 693 (%) | Yes, n = 48 (%) | ||
| Type of procedure | 0.814 | ||
| Isolated AVR | 487 (70.3) | 31 (65) | |
| AVR plus coronary artery bypass grafting | 55 (7.9) | 4 (8) | |
| AVR plus mitral valve procedure | 85 (12.3) | 8 (17) | |
| AVR plus other major procedure | 66 (9.5) | 5 (10) | |
| Mechanical valve prosthesis | 301 (43.4) | 21 (44) | 0.966 |
| Minimally invasive approach | 13 (1.9) | 0 | 1.000 |
| Aortic cross-clamping time (minutes) | 95 ± 44 | 119 ± 54 | 0.004 |
| Cardiopulmonary bypass time (minutes) | 142 ± 62 | 175 ± 80 | 0.011 |
The risk of stroke was stratified by the CHA 2 DS 2 -VASc score, which has been previously validated in patients undergoing coronary artery bypass surgery. Patients with CHA 2 DS 2 -VASc score of ≥2 were considered at high risk of stroke.
The main end point of this study was in-hospital stroke defined as postoperative cerebrovascular accident in which symptoms lasted >24 hours with or without residual disability confirmed at computed tomography or magnetic resonance imaging. In case of no evidence of stroke at imaging, the diagnosis of stroke was made by 1 or 2 consulting independent neurologists. We assessed also all-cause mortality of these patients to evaluate the impact of perioperative stroke on late outcome.
Statistical analysis was performed using an SPSS version 20 statistical software (IBM SPSS Inc., Chicago, Illinois). Fisher’s exact, chi-square, and Mann-Whitney tests were used for univariate analysis. No attempt to replace missing values was made. Multivariate analysis was performed using stepwise logistic regression and Cox proportional hazards methods with backward selection. Only variables with a p <0.05 at univariate analysis were included in the regression models to avoid overfitting. Hosmer-Lemeshow test was used to assess the regression model fit. The area under the receiver operating characteristic curve was used to represent the discriminatory ability of the regression models. A p <0.05 was considered statistically significant.
Results
In-hospital mortality in this series was 5.5% and 5-year survival was 78.6%. Forty-eight patients (6.5%; after isolated AVR, 6.0%) suffered stroke immediately after surgery and 10 of them died during hospitalization (20.8%). The hospital mortality among patients without postoperative stroke was 4.5% (adjusted for additive EuroSCORE: p = 0.001, odds ratio [OR] 4.266, 95% confidence interval [CI] 1.856 to 9.807). Patients who suffered stroke after surgery had significantly higher rate of low cardiac output syndrome (54.2% vs 13.3%, p <0.0001), tracheal intubation time of >48 hours (12.7% vs 68.8%, p <0.0001), renal replacement therapy (25.0% vs 5.6%, p <0.0001), deep sternal wound infection (6.3% vs 1.3%, p = 0.037), longer intensive care unit stay (13.7 ± 16.2 vs 3.8 ± 5.8 days, p <0.0001), and in-hospital stay (25.0 ± 22.4 vs 12.2 ± 8.0 days, p <0.0001).
Univariate analysis showed that a number of baseline characteristics and operative variables ( Tables 1 and 2 ) were associated with immediate postoperative stroke. Cardiopulmonary bypass time was dichotomized according to the results of tree analysis (cut-off value, 217 minutes) and finding of a previous study indicating an increased risk of stroke for cardiopulmonary bypass time of >210 minutes. We observed that perioperative use of intra-aortic balloon pump (22.9% vs 5.3%, p <0.0001), cardiopulmonary bypass time of >210 minutes (15.7% vs 5.0%, p <0.0001), blood products transfusion (9.3% vs 0.8%, p <0.0001), and reexploration for bleeding (24.0% vs 5.2%, p <0.0001) were associated with an extremely high risk of postoperative stroke. Excessive bleeding in patients with postoperative stroke was driven by the significantly higher rate of major injuries to vascular and cardiac structures at reentry in these patients (18.8% vs 4.5%, p <0.0001).
Logistic regression showed that female gender (p = 0.004, OR 2.569, 95% CI 1.358 to 4.857), emergency procedure (p = 0.016, OR 2.633, 95% CI 1.119 to 5.784), use of intra-aortic balloon pump (p = 0.022, OR 2.673, 95% CI 1.154 to 6.190), cardiopulmonary bypass time of >210 minutes (p = 0.022, OR 2.313, 95% CI 1.131 to 4.713), use of blood products (p = 0.006, OR 7.752, 95% CI 1.825 to 32.934), and reexploration for excessive bleeding (p <0.0001, OR 4.844, 95% CI 2.178 to 10.773; Hosmer-Lemeshow test: p = 0.542, area under the receiver operating characteristic curve 0.808, 95% CI 0.747 to 0.870) were all independent predictors of postoperative stroke. These findings were confirmed in a regression model including a CHA 2 DS 2 -VASc score of ≥2, which itself was an independent predictor of stroke (8.2% vs 1.6%, p = 0.015, OR 4.520, 95% CI 1.338 to 15.276).
Actuarial analysis showed that survival at 3 years among patients who experienced postoperative stroke was 51.9% (16 patients entering interval), whereas it was 85.0% (318 patients entering interval) among those without postoperative stroke (log-rank p <0.0001). Cox proportional hazards model showed that when adjusted for male gender (p = 0.042, relative risk [RR] 1.473, 95% CI 1.014 to 2.141), S-AVR combined with coronary artery bypass grafting (p <0.0001, RR 2.667, 95% CI 1.660 to 4.284), left ventricular ejection fraction of <30% (p <0.0001, RR 4.786, 95% CI 3.057 to 7.493), and acute infective endocarditis (p <0.0001, RR 3.857, 95% CI 2.749 to 5.411), postoperative stroke was an independent predictor of late all-cause mortality (p <0.0001, RR 2.965, RR 1.862 to 4.722; Figure 1 ). Immediate postoperative stroke (p <0.0001, RR 2.865, RR 1.793 to 4.579) was a determinant of all-cause mortality also when adjusted only for additive EuroSCORE (p <0.0001, RR 1.152, 95% CI 1.100 to 1.205).
