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The Penn Classification Predicts Hospital Mortality in Acute Stanford Type A and Type B Aortic Dissections
ARTICLE IN PRESS Journal of Cardiothoracic and Vascular Anesthesia 000 (2019) 1 7
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Original Article
The Penn Classification Predicts Hospital Mortality in Acute Stanford Type A and Type B Aortic Dissections Michael Tien, MD, Andrew Ku, BA, Natalia Martinez-Acero, MD, Jessica Zvara, MD, Eric C. Sun, MD, PhD, Albert T. Cheung, MD* Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA
Objectives: Mortality in acute aortic dissection varies depending on anatomic location, extent, and associated complications. The Stanford classification guides surgical versus medical management. The Penn classification stratifies mortality risk in patients with Stanford type A aortic dissections undergoing surgery. The objective of the present study was to determine whether the Penn classification can predict hospital mortality in patients with acute Stanford type A and type B aortic dissections undergoing surgical or medical management. Design: Retrospective, observational study. Setting: Tertiary care, university hospital. Participants: Patients with acute aortic dissection between January 2008 and December 2017. Interventions: Examination of hospital mortality after surgical or medical management. Measurements and Main Results: Three hundred fifty-two patients had confirmed dissections (186 type A, 166 type B). The overall mortality was 18.8% for type A and 13.3% for type B. Penn class A patients with type A or type B dissections undergoing surgical repair had the lowest mortality (both 3.1%). Penn class B, C, or B+C patients with type A dissections and Penn class B+C patients with type B dissections undergoing medical management had the greatest incidence of mortality (50.0%-57.1%). All others had intermediate mortality (6.7%-39.3%). Logistic regression analysis demonstrated that Penn class B, C, and B+C patients had a greater odds of mortality and predicted mortality than did Penn class A patients. Conclusions: The Penn classification predicts hospital mortality in patients with acute Stanford type A or type B aortic dissections undergoing surgical or medical management. Early endovascular repair may confer lower risk of mortality in patients with type B dissections presenting without ischemia. Ó 2019 Elsevier Inc. All rights reserved. Key Words: aortic dissection; Stanford classification; Stanford type A; Stanford type B; Penn classification; hospital mortality
ACUTE AORTIC dissection can be life-threatening and often is associated with a high risk of early mortality. In 1965, DeBakey et al. reported improved outcomes after surgical repair based on the location and extent of the dissection.1 In 1970, the clinical experience from Stanford University Hospital indicated that mortality and prognosis for dissections involving the ascending aorta E. Sun has received funding (K08DA042314) from the National Institute on Drug Abuse, Rockville, MD, and consulting fees from Egalet Corporation, Wayne, PA, and the Mission LISA Foundation, Tampa, FL. * Address reprint requests to Albert T. Cheung, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Dr., H3578, Stanford, CA 94305. E-mail address: [email protected] (A.T. Cheung). https://doi.org/10.1053/j.jvca.2019.08.036 1053-0770/Ó 2019 Elsevier Inc. All rights reserved.
were distinct from dissections limited to the descending aorta.2 The initial experience from the International Registry for Aortic Dissection confirmed that patients with Stanford type A dissections involving the ascending aorta had improved survival in response to surgical repair.3 In contrast, patients with Stanford type B dissections limited to the descending aorta had improved survival in response to medical therapy. For this reason, the Stanford classification, based on the anatomic location and extent of the dissection, serves as a useful guide to determine whether patients should be treated emergently with surgical repair or conservatively with medical management.2 Despite this approach, there remains substantial variability in hospital mortality among patients appropriately treated for type A or type B aortic dissections.2,3
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To address the differences in mortality among patients undergoing surgical treatment for type A dissections, the Penn classification was developed to stratify patients based on their ischemic pattern or pathophysiologic condition at time of presentation.4,5 The Penn classification improved outcome prediction among this group of patients based on the presence or absence of branch-vessel malperfusion, circulatory collapse, or both.4 Only a small number of international studies have validated the utility of the Penn classification to predict mortality in patients with type A dissections undergoing surgical repair.6-9 Furthermore, the utility of the Penn classification for stratifying hospital mortality risk in patients with type B dissections is unclear despite some evidence that ischemic complications also have a prognostic effect in this condition.10 The recent development of endovascular repair techniques for type B dissections and expanded range of surgical repairs that can be performed in current practice make it important to subclassify patients into low- and high-risk groups for more nuanced clinical decision making.11-13 Thus, the aim of the present study was to determine whether the Penn classification could be used to stratify hospital mortality risk in patients with either acute Stanford type A or type B aortic dissections undergoing either surgical or medical management. The secondary objective was to identify additional risk factors for hospital mortality in the contemporary management of acute aortic dissection. Methods Patient Identification With Institutional Review Board approval, a single-center retrospective investigation was performed. All patients admitted or transferred to the authors’ tertiary care, university-affiliated hospital with a diagnosis of possible acute aortic dissection from January 2008 to December 2017 were identified from the institutional database. After manual chart review, patients were ultimately included if they had a new diagnosis of acute aortic dissection documented in the electronic medical record (EMR) based on clinical findings (eg, sudden onset of sharp or tearing chest, thoracic or abdominal pain, pulse or blood pressure discrepancy between right and left arm) and new imaging evidence of an aortic dissection flap separating the false lumen from the true lumen, intramural hematoma or entry tear, or penetrating ulcer on computed tomography or transesophageal echocardiography.14-17 Patients with an incorrect diagnosis or with no radiographic confirmation of acute aortic dissection were excluded from the final analysis. Patients with known or preexisting aortic dissections before the index hospitalization (noted in the EMR or with evidence on prior imaging studies) were classified as having a chronic dissection and also were excluded. Data Abstraction and Definitions Data were reviewed and collected by 3 authors (M.T., N. M.A., J.Z.), and 5 of the authors were involved in data analysis (M.T., A.K., N.M.A., E.S., A.T.C.). In addition to obtaining
data contained within the institutional database, the EMR of each patient was reviewed manually to collect data on baseline patient characteristics, preexisting comorbidities, whether the dissection was treated medically or surgically, hospital course, complications, and hospital mortality. All aortic dissections were classified as Stanford type A if they involved the ascending aorta and Stanford type B if the involvement was limited to the descending aorta. Medical management was defined as nonsurgical treatment with medications exclusively during the course of the hospitalization. Surgical management was defined as surgical treatment by open or endovascular repair during the index hospitalization. All patients were stratified based on their condition at the time of presentation according to the Penn classification as follows: Penn class A indicating the absence of malperfusion or circulatory collapse, Penn class B indicating the presence of branch-vessel malperfusion, Penn class C indicating the presence of circulatory collapse, and Penn class B+C indicating the presence of both branch-vessel malperfusion and circulatory collapse.4 The criteria used to define branch-vessel malperfusion (Penn class B) were the presence of any of the following: stroke; paraplegia; new-onset lower extremity weakness or paralysis; upper or lower extremity pulse deficits; need for vascular surgery to restore blood flow to the extremities; acute kidney injury (AKI), defined as serum creatinine greater than 2 times the baseline, glomerular filtration rate reduction by more than 50% at time of admission, urine output less than 0.5 mg/kg/h in the first 12 hours, or new need for renal replacement therapy; mesenteric ischemia, malperfusion to the celiac trunk, superior mesenteric artery, or inferior mesenteric artery with either radiographic evidence or clinical findings of an acute abdomen; need for emergency bowel resection; or acute gastrointestinal bleeding resulting from ischemic colitis (Table 1). The criteria used to define circulatory collapse (Penn class C) were the presence of any of the following: newly reduced left ventricular ejection fraction less than 50%, new right ventricular dysfunction, pericardial tamponade, acute coronary ischemia, myocardial infarction, or need for intra-aortic balloon pump or venoarterial extracorporeal membrane oxygenation support (see Table 1). The criteria for Penn class B+C were defined as patients who presented with at least 1 criterion for both Penn class B and class C. Criteria for Penn class A were defined as patients without any of the conditions associated with Penn class B or class C at the time of presentation. Statistical Analysis All statistical analyses were conducted in consultation with a statistician (E.S.). The primary objective was to determine whether the Penn classification predicts hospital mortality in patients with either acute Stanford type A or type B aortic dissection undergoing either medical or surgical management. Observed mortality rates in the patient population are reported along with 95% confidence intervals (CIs) estimating the binomial approximation of the true proportion. The secondary objective was to identify other risk factors (related to branch-vessel
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Table 1 Criteria Used for Penn Classification System Penn Classification
Criteria
Penn class A Penn class B
Absence of malperfusion (class B) or circulatory collapse (class C) Branch-vessel malperfusion: ▪ Stroke ▪ Paraplegia ▪ New-onset lower extremity weakness or paralysis ▪ Upper or lower extremity pulse deficits
Penn class C
▪ Need for vascular surgery to restore blood flow to the extremities ▪ Acute kidney injury, defined as serum creatinine greater than 2 times baseline, glomerular filtration rate reduction by more than 50%, urine output less than 0.5 mg/kg/h in the first 12 h, or new need for renal replacement therapy ▪ Mesenteric ischemia; malperfusion to the celiac trunk, superior mesenteric artery, or inferior mesenteric artery with either radiographic evidence or clinical findings of an acute abdomen; need for emergency bowel resection; or acute gastrointestinal bleeding owing to ischemic colitis Circulatory collapse: ▪ Newly reduced left ventricular ejection fraction <50% ▪ New right ventricular dysfunction ▪ Pericardial tamponade ▪ Acute coronary ischemia ▪ Myocardial infarction ▪ Need for intra-aortic balloon pump
Penn class B + C
▪ Need for venoarterial extracorporeal membrane oxygenation Meeting at least 1 criterion for malperfusion (class B) and circulatory collapse (class C)
malperfusion, circulatory collapse, or unrelated to ischemic complications) associated with hospital mortality in acute aortic dissections. Logistic regression analysis was used to determine the odds ratio (OR) and 95% CI for hospital mortality and predicted mortality for each Penn class, adjusting for Stanford classification and whether patients were treated with surgery. Differences in mortality rate as a function of calendar time were assessed using logistic regression analysis. For patients who died, one-way analysis of variance was used to assess for differences in mean time to death among Penn classes. Chi-square tests and univariate analyses were used to test the significance of risk factors predicting hospital mortality. All data were analyzed using STATA statistical software, Version 14.0 (StataCorp, LLC, College Station, TX). In all cases, 2-tailed p values < 0.05 were considered to be statistically significant.
For patients who died, the mean (§ standard deviation) time to death with type A dissections was 2.4 § 2.1 days for Penn class A, 12.4 § 19.3 days for Penn class B, 3.7 § 4.0 days for Penn class C, and 11.2 § 9.4 days for Penn class B+C (p = 0.27). The mean time to death for patients with type B dissection was 4.1 § 5.4 days for Penn class A, 7.9 § 8.4 days for Penn class B, and 7.0 § 4.4 days for Penn class B+C (p = 0.52). There was no significant trend or differences in hospital mortality rates over calendar time over the 10-year study period, as stratified by type A overall (p = 0.25), type A with
Results A total of 508 patients were initially identified from the authors’ database as being admitted with possible acute aortic dissection between January 2008 and December 2017. Among the 508 patients, 156 were excluded because of an incorrect diagnosis (n = 47), chronic dissection (n = 19), or inability to confirm the diagnosis of acute aortic dissection based on manual review of imaging studies (n = 90). A total of 352 patients, 186 with acute Stanford type A and 166 acute type B aortic dissections were included in the final analysis (Fig 1). The summary statistics of the patient population are displayed in Table 2. The overall hospital mortality was 18.8% (95% CI 13.5%-25.2%) for patients with type A dissections and 13.3% (95% CI 8.5%-19.4%) for patients with type B dissections (Table 3).
Fig 1. Flow diagram of patient selection and exclusion criteria.
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Table 2 Summary Statistics for Patients With Acute Aortic Dissection Between January 2008 and December 2017
Mean age (y) Male Female Diabetes mellitus Chronic kidney disease Penn class A Penn class B Penn class C Penn class B+C Medical management Surgical management Hospital mortality
Stanford Type A (n = 186)
Stanford type B (n = 166)
All (n = 352)
62.9 (15.6) 123 (66.1%) 63 (33.9%) 7 (3.8%) 24 (12.9%)
58.9 (15.3) 114 (68.7%) 52 (31.3%) 9 (5.4%) 13 (7.8%)
61.0 (15.6) 237 (67.3%) 115 (32.7%) 16 (4.5%) 37 (10.5%)
81 (43.5%) 56 (30.1%) 19 (10.2%) 30 (16.1%) 29 (15.6%)
114 (68.7%) 42 (25.3%) 4 (2.4%) 6 (3.6%) 100 (60.2%)
195 (55.4%) 98 (27.8%) 23 (6.5%) 36 (10.2%) 129 (36.6%)
157 (84.4%)
66 (39.8%)
223 (63.3%)
35 (18.8%)
22 (13.3%)
57 (16.2%)
NOTE. Data are reported as mean and standard deviation or as n and percent. Stanford Type A is defined as aortic dissection involving the ascending aorta. Stanford Type B is defined as aortic dissection confined to the descending aorta. Penn class A, the absence of branch-vessel malperfusion and circulatory collapse. Penn class B, branch-vessel malperfusion. Penn class C, circulatory collapse. Penn class B+C, both branch-vessel malperfusion and circulatory collapse.
surgical management (p = 0.56), type B overall (p = 0.49), and type B with surgical management (p = 0.42). Of all patients in this study, 44.6% (157/352) experienced associated complications and were classified as Penn class B, C, or B+C. The remaining 55.4% (195/352) of patients experienced no acute complications at the time of presentation and were classified as Penn class A. The lowest hospital mortality rate was observed among Penn class A patients undergoing surgical repair for type A dissections (3.1% [95% CI 0.4%10.7%]) and type B dissections (3.1% [95% CI 0.1%-16.2%]). The highest hospital mortality rates were observed among medically managed patients with type A dissections in Penn class B (57.1% [95% CI 18.4%-90.1%]), class C (50.0% [95% CI 6.8%-93.2%]), or class B+C (50.0% [95% CI 1.3%98.7%]) and in medically managed patients with type B dissections in Penn class B+C (50.0% [95% CI 1.3%-98.7%]) (see
Table 3). All other patients had intermediate hospital mortality rates in the range of 6.7% (95% CI 0.2%-31.9%) to 39.3% (95% CI 21.5%-59.4%) (see Table 3). Logistic regression analysis, adjusted for whether or not patients had surgical repair, demonstrated that for all aortic dissections, Penn class B (OR 7.9, 95% CI 3.6-17.4; p < 0.001) and Penn class B+C (OR 14.2, 95% CI 5.4-37.7; p < 0.001) were associated with higher odds of hospital mortality compared with Penn class A (Table 4). For all dissections, Penn class C patients had higher odds of mortality compared with patients with Penn class A, but the difference was not quite statistically significant (OR 3.1, 95% CI 0.8-12.3; p = 0.111). Among patients with type A dissections, Penn class B (OR 5.6, 95% CI 1.9-16.4; p = 0.002) and Penn class B+C patients (OR 10.1, 95% CI 3.2-32.4; p < 0.001) had greater odds of hospital mortality compared with Penn class A patients (see Table 4). Similarly, among patients with type B dissections, Penn class B (OR 6.9, 95% CI 2.5-18.7; p < 0.001) and Penn class B+C (OR 7.6, 95% CI 1.2-49.2; p = 0.032) patients had greater odds of mortality compared with patients in Penn class A (see Table 4). Predicted mortality rates by Stanford type and Penn classifications of the study population are shown in Table 5. The predicted mortality rates for Penn class A dissections were 5.2% (95% CI 2.1%-8.3%) overall, 6.2% (95% CI 0.9%-11.4%) for type A dissections, and 6.1% (95% CI 1.7%-10.5%) for type B dissections. The predicted mortality rates for Penn class B dissections were 30.3% (95% CI 20.8%-39.8%) overall, 26.8% (95% CI 15.2%-38.4%) for type A dissections, and 30.9% (95% CI 17.0%-44.9%) for type B dissections. The predicted mortality rates for Penn class C dissections were 14.4% (95% CI 0.0%-29.6%) overall, 15.8% (95% CI 0.0%-32.2%) for type A dissections, and indeterminate for type B dissections (there were no deaths in the group of patients with Penn class C, type B aortic dissections to generate a statistical estimate). The predicted mortality rates for Penn class B+C dissections were 43.8% (95% CI 26.6%-60.9%) overall, 40.0% (95% CI 22.5%-57.5%) for type A dissections, and 33.3% (95% CI 0.0%-71.1%) for type B dissections. In addition to the Penn classification, the following univariate risk factors were associated with a greater risk of mortality
Table 3 Hospital Mortality Among Patients Admitted With Acute Aortic Dissection Between January 2008 and December 2017 According to Stanford Type, Medical Versus Surgical Management, and Penn Classification
Stanford type A Overall Medical Surgical Stanford type B Overall Medical Surgical
All
Penn A
Penn B
Penn C
Penn B + C
35/186 (18.8%) 10/29 (34.4%) 25/157 (15.9%)
5/81 (6.2%) 3/16 (18.8%) 2/65 (3.1%)
15/56 (26.8%) 4/7 (57.1%) 11/49 (22.4%)
3/19 (15.8%) 2/4 (50.0%) 1/15 (6.7%)
12/30 (40.0%) 1/2 (50.0%) 11/28 (39.3%)
13/42 (30.9%) 4/16 (25.0%) 9/26 (34.6%)
0/4 (0.0%) 0/0 (n/a) 0/4 (0.0%)
22/166 (13.3%) 11/100 (11.0%) 11/66 (16.7%)
7/114 (6.1%) 6/82 (7.3%) 1/32 (3.1%)
2/6 (33.3%) 1/2 (50.0%) 1/4 (25.0%)
NOTE. Data are reported as mean and standard deviation or as n and percent. Stanford Type A is defined as aortic dissection involving the ascending aorta. Stanford Type B is defined as aortic dissection confined to the descending aorta. Penn class A, the absence of branch-vessel malperfusion and circulatory collapse. Penn class B, branch-vessel malperfusion. Penn class C, circulatory collapse. Penn class B+C, both branch-vessel malperfusion and circulatory collapse.
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Table 4 Logistic Regression Analysis for Hospital Mortality by Stanford Type and Penn Classification Using Penn Class A as the Reference Group Penn B
Overall Stanford Type A Stanford Type B
Penn C
Penn B + C
OR (95% CI)
p Value
OR (95% CI)
p Value
OR (95% CI)
p Value
7.9 (3.6-17.4) 5.6 (1.9-16.4) 6.9 (2.5-18.7)
<0.001 0.002 <0.001
3.1 (0.8-12.3) 2.9 (0.6-13.2) Omitted*
0.111 0.180 Omitted*
14.2 (5.4-37.7) 10.1 (3.2-32.4) 7.6 (1.2-49.2)
<0.001 <0.001 0.032
NOTE. Data are reported as odds ratios (OR) and 95% confidence interval (95% CI). Stanford Type A is defined as aortic dissection involving the ascending aorta. Stanford Type B is defined as aortic dissection confined to the descending aorta. Penn class A, the absence of branch-vessel malperfusion and circulatory collapse. Penn class B, branch-vessel malperfusion. Penn class C, circulatory collapse. Penn class B+C, both branch-vessel malperfusion and circulatory collapse. * No deaths encountered in Penn class C, Stanford type B, thus the logistic regression omitted this group from the analysis.
Table 5 Predicted Mortality by Stanford Type and Penn Classification Penn A
Overall Stanford type A Stanford type B
Penn B
Penn C
Penn B + C
Predicted Mortality (95% CI)
SE
Predicted Mortality (95% CI)
SE
Predicted Mortality (95% CI)
SE
Predicted Mortality (95% CI)
SE
5.2% (2.1%-8.3%) 6.2% (0.9%-11.4%) 6.1% (1.7%-10.5%)
1.6% 2.7% 2.2%
30.3% (20.8%-39.8%) 26.8% (15.2%-38.4%) 30.9% (17.0%-44.9%)
4.8% 5.9% 7.1%
14.4% (0.0%-29.6%) 15.8% (0.0%-32.2%) Omitted*
7.7% 8.4% Omitted*
43.8% (26.6%-60.9%) 40.0% (22.5%-57.5%) 33.3% (0.0%-71.1%)
8.8% 8.9% 19.2%
NOTE. Data are reported as predicted mortality (%) and 95% confidence interval (95% CI). Stanford Type A is defined as aortic dissection involving the ascending aorta. Stanford Type B is defined as aortic dissection confined to the descending aorta. Penn class A, the absence of branch-vessel malperfusion and circulatory collapse. Penn class B, branch-vessel malperfusion. Penn class C, circulatory collapse. Penn class B+C, both branch-vessel malperfusion and circulatory collapse. Abbreviation: SE, standard error. * No deaths encountered in Penn class C, Stanford type B, thus the logistic regression omitted this group from the analysis.
for all acute dissections: older age (mean age 70.2 v 61.2; p < 0.001), AKI (p = 0.040), lactic acidosis (p < 0.001), mesenteric ischemia (p < 0.001), stroke (p < 0.001), pericardial tamponade (p = 0.026), myocardial ischemia (p = 0.018), cardiac arrest (p < 0.001), new-onset seizures (p < 0.001), and prolonged mechanical ventilation (p < 0.001). Female sex (p < 0.001) and medical management (p = 0.019) were associated with greater mortality for patients with type A dissections. There was no significant difference in mortality when comparing type of surgery performed (p = 0.87) and cerebral perfusion technique (p = 0.72) used to perform the surgeries. Discussion A large proportion of patients with acute aortic dissection present with various life-threatening complications that contribute to the variability in mortality associated with this condition. The present study demonstrates that the Penn classification is a valuable tool to predict hospital mortality among patients with Stanford type A or type B aortic dissections undergoing either surgical or medical management. The lowest mortality rates were found among Penn class A patients with type A and type B dissections undergoing surgical management and among the 44.6% of patients presenting with branch-vessel malperfusion, circulatory collapse, or both; the overall risk of mortality was increased by a factor of 7.9-fold, 3.1-fold, or 14.2-fold, respectively. Prior studies examining predictors of mortality in aortic dissections have reported on factors predominantly related to ischemic complications on presentation (eg, hypotension,
shock, mesenteric ischemia, AKI, limb ischemia, pulse deficit, myocardial ischemia or infarction).18-24 Augoustides et al. proposed classifying patients undergoing surgery for type A dissections based on the pattern of preoperative ischemia and reported hospital mortality rates of 3.1% for Penn class A, 25.6% for Penn class B, 17.6% for Penn class C, and 40.0% for Penn class B+C.4 Retrospective studies from Sweden, Japan, and Italy subsequently demonstrated similar results.6-9 The results of the present study are consistent with prior data and demonstrate similar effectiveness of the Penn classification in predicting mortality in patients with type B dissections. The findings in the present study support the general recommendation that surgical repair is the best option for patients with type A dissections and medical management is the best option for patients with type B dissections.2 However, application of the Penn classification provided additional insights into subtle differences in outcomes. For example, among the 29 patients with type A dissection treated medically, the survival rate for the 16 patients who were in Penn class A was 81.3% compared with the combined survival rate for the 13 patients who were in Penn class B, C, or B+C of only 46.2%. This finding suggests that medical management may be an acceptable option for patients with uncomplicated type A dissections for whom surgery may be too risky for other reasons (eg, advanced age, frailty, malignancy, dementia, hemorrhagic stroke). Another finding revealed by the Penn classification was that among the 114 patients with type B dissections in Penn class A, hospital mortality was lowest among those treated surgically (3.1%), a rate that was much lower than those treated
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medically (7.3%). Even though more data are needed, this finding suggests that early surgical or endovascular repair may confer a mortality benefit to a specific subset of patients with uncomplicated type B dissections. Thus, use of the Penn classification may lead to more nuanced clinical decision making regarding the potential risks and benefits of surgical versus medical management for both type A and type B dissections. Even though the patients in the present study were managed at a single hospital and no significant trends in mortality over time were observed, it is important to note that changes over the last decade in surgical technique and perioperative management may have influenced mortality rates that cannot be fully explained by the Stanford or Penn classification schemes. In fact, there are data to suggest that later year of surgery for patients with type A dissections was associated with decreased mortality.25 The absence of any significant trends in mortality in this study may be explained by the relatively limited number of patients with hospital mortality, a stable practice pattern within a single referral center, and the clinical availability of the full spectrum of endovascular repair techniques at the institution over the study period. Advancements in endovascular repair techniques for both type A and type B dissections have provided older, higher-risk patients a chance to benefit from surgical repair.11-13,26,27 It is possible that the improved survival seen among patients with uncomplicated type B dissections treated with surgery in the present study may be the consequence of these developments. Furthermore, the ideal management of aortic dissections complicated by malperfusion syndromes continues to evolve. Yang et al. reported reduced mortality with a staged repair consisting of upfront endovascular fenestration/stenting to establish reperfusion, followed by delayed open aortic repair for a subset of patients with relatively stable conditions.28,29 Leshnower et al. also reported survival benefits with similar staged repairs.30,31 These newer techniques have yet to be widely adopted and were not routinely used during the time of the present study. In addition, there has been a recent paradigm shift to manage patients with aortic dissections in a hybrid catheterization laboratory/operating room environment where the skill sets of cardiothoracic surgeons, interventional cardiologists, and cardiothoracic anesthesiologists can be integrated to simultaneously obtain hemodynamic control, perform noninvasive and invasive diagnostic studies, and provide immediate surgical or endovascular therapies all in a single clinical workspace while minimizing any delay.32,33 Even though the majority of patients in the present study with type B dissections undergoing endovascular repair were managed in a hybrid operating room, this approach was not routine for patients with type A dissections, who were mostly managed in a traditional operating room setting. The findings of this study should be interpreted in the context of its limitations as a retrospective observational study. Thus, the quality of the data is reliant on accuracy and completeness of the EMR and institutional database. In addition, stratification of patients into Penn classes was based on manual chart review rather than direct examination of patients. Finally, this study was conducted at a single referral center that specializes in the management of acute aortic dissection and the applicability of the findings to other clinical settings is unclear.
In conclusion, the Penn classification is useful in predicting mortality in patients with type A and type B dissections undergoing medical or surgical management and allows for more nuanced clinical decision making. The authors found that surgery was generally the best option for patients with type A dissections, but the survival rate among a small subset of patients with uncomplicated type A dissections managed medically was acceptable. In addition, the mortality rate for patients with complicated type B dissections was not significantly different among those treated medically or surgically. However, the mortality rate was lower among patients with uncomplicated type B dissections who were treated surgically compared with those treated medically. Additional studies are needed to confirm these findings before any changes to clinical practice can be recommended. Declaration of Competing Interest The authors report no financial interests nor conflicts of interest pertaining to the contents of this article. Dr. Eric C. Sun has an affiliation with the Department of Health Research and Policy, Stanford University School of Medicine. References 1 Debakey ME, Henly WS, Cooley DA, et al. Surgical management of dissecting aneurysms of the aorta. J Thorac Cardiovasc Surg 1965;49:130–49. 2 Daily PO, Trueblood HW, Stinson EB, et al. Management of acute aortic dissections. Ann Thorac Surg 1970;10:237–47. 3 Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): New insights into an old disease. JAMA 2000;283:897–903. 4 Augoustides JGT, Geirsson A, Szeto WY, et al. Observational study of mortality risk stratification by ischemic presentation in patients with acute type A aortic dissection: The Penn classification. Nat Clin Pract Cardiovasc Med 2009;6:140–6. 5 Augoustides JGT, Szeto WY, Desai ND, et al. Classification of acute type A dissection: Focus on clinical presentation and extent. Eur J Cardiothorac Surg 2011;39:519–22. 6 Olsson C, Hillebrant C-G, Liska J, et al. Mortality in acute type A aortic dissection: Validation of the Penn Classification. Ann. Thorac Surg 2011;92:1376–82. 7 Kimura N, Ohnuma T, Itoh S, et al. Utility of the Penn Classification in predicting outcomes of surgery for acute type A aortic dissection. Am J Cardiol 2014;113:724–30. 8 Danielsson E, Zindovic I, Bjursten H, et al. Generalized ischaemia in type A aortic dissections predicts early surgical outcomes only. Interact Cardiovasc Thorac Surg 2015;21:583–9. 9 Pisano C, Balistreri CR, Torretta F, et al. Penn classification in acute aortic dissection patients. Acta Cardiol 2016;71:235–40. 10 Augoustides JGT, Szeto WY, Woo EY, et al. The complications of uncomplicated acute type-B dissection: The introduction of the Penn classification. J Cardiothorac Vasc Anesth 2012;26:1139–44. 11 Alfson DB, Ham SW. Type B aortic dissections: Current guidelines for treatment. Cardiol Clin 2017;35:387–410. 12 Cooper M, Hicks C, Ratchford EV, et al. Diagnosis and treatment of uncomplicated type B aortic dissection. Vasc Med 2016;21:547–52. 13 Clough RE, Nienaber CA. Evidence for and risks of endovascular treatment of asymptomatic acute type B aortic dissection. J Cardiovasc Surg (Torino) 2017;58:270–7. 14 von Kodolitsch Y, Schwartz AG, Nienaber CA. Clinical prediction of acute aortic dissection. Arch Intern Med 2000;160:2977–82. 15 Kienzl D, Prosch H, T€opker M, et al. Imaging of non-cardiac, non-traumatic causes of acute chest pain. Eur J Radiol 2012;81:3669–74.
ARTICLE IN PRESS M. Tien et al. / Journal of Cardiothoracic and Vascular Anesthesia 00 (2019) 1 7 16 Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation 2010;121:e266–369. 17 Erbel R, Aboyans V, Boileau C, et al. Corrigendum to: 2014 ESC guidelines on the diagnosis and treatment of aortic diseases. Eur Heart J 2015;36:2779. 18 Trimarchi S, Nienaber CA, Rampoldi V, et al. Contemporary results of surgery in acute type A aortic dissection: The International Registry of Acute Aortic Dissection experience. J Thorac Cardiovasc Surg 2005;129:112–22. 19 Rampoldi V, Trimarchi S, Eagle KA, et al. Simple risk models to predict surgical mortality in acute type A aortic dissection: The International Registry of Acute Aortic Dissection score. Ann. Thorac Surg 2007; 83:55–61. 20 Mehta RH, Suzuki T, Hagan PG, et al. Predicting death in patients with acute type A aortic dissection. Circulation 2002;105:200–6. 21 Pansini S, Gagliardotto PV, Pompei E, et al. Early and late risk factors in surgical treatment of acute type A aortic dissection. Ann Thorac Surg 1998;66:779–84. 22 Chiappini B, Schepens M, Tan E, et al. Early and late outcomes of acute type A aortic dissection: Analysis of risk factors in 487 consecutive patients. Eur Heart J 2005;26:180–6. 23 Genoni M, Paul M, Tavakoli R, et al. Predictors of complications in acute type B aortic dissection. Eur J Cardiothorac Surg 2002;22:59–63.
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24 Tolenaar JL, Froehlich W, Jonker FHW, et al. Predicting in-hospital mortality in acute type B aortic dissection: Evidence from International Registry of Acute Aortic Dissection. Circulation 2014;130:S45–50. 25 Geirsson A, Ahlsson A, Franco-Cereceda A, et al. Hospital volumes and later year of operation correlates with better outcomes in acute type A aortic dissection. Eur J Cardiothorac Surg 2018;53:276–81. 26 Kreibich M, Rylski B, Czerny M, et al. Influence of age and the burden of ischemic injury on the outcome of type A aortic dissection repair [E-pub ahead of print]. Ann Thorac Surg 2019 June 5. 27 Harky A, Chan JSK, Wong CHM, et al. Systematic review and meta-analysis of acute type B thoracic aortic dissection, open, or endovascular repair. J Vasc Surg 2019;69;1599-1609.e2. 28 Yang B, Rosati CM, Norton EL, et al. Endovascular fenestration/stenting first followed by delayed open aortic repair for acute type A aortic dissection with malperfusion syndrome. Circulation 2018;138:2091–103. 29 Yang B, Norton EL, Rosati CM, et al. Managing patients with acute type A aortic dissection and mesenteric malperfusion syndrome: A 20-year experience. J Thorac Cardiovasc Surg 2019;158:675–87. 30 Leshnower BG, Veeraswamy RK, Duwayri YM, et al. The “TEVAR-first” approach to DeBakey I aortic dissection with mesenteric malperfusion. Ann Thorac Surg 2014;97:693–6. 31 Leshnower BG, Keeling WB, Duwayri YM, et al. The “thoracic endovascular aortic repair-first” strategy for acute type A dissection with mesenteric malperfusion: Initial results compared with conventional algorithms [E-pub ahead of print]. J Thorac Cardiovasc Surg 2019 Feb 11. 32 Augoustides JGT, Patel PA, Savino JS, et al. The heart team approach to acute type A dissection: A new paradigm in the era of the integrated Penn classification and the Essen concept. Eur J Cardiothorac Surg 2013;43:404–5. 33 Tsagakis K, Konorza T, Dohle DS, et al. Hybrid operating room concept for combined diagnostics, intervention and surgery in acute type A dissection. Eur J Cardiothorac Surg 2013;43:397–404.
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Original Article
The Penn Classification Predicts Hospital Mortality in Acute Stanford Type A and Type B Aortic Dissections Michael Tien, MD, Andrew Ku, BA, Natalia Martinez-Acero, MD, Jessica Zvara, MD, Eric C. Sun, MD, PhD, Albert T. Cheung, MD* Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA
Objectives: Mortality in acute aortic dissection varies depending on anatomic location, extent, and associated complications. The Stanford classification guides surgical versus medical management. The Penn classification stratifies mortality risk in patients with Stanford type A aortic dissections undergoing surgery. The objective of the present study was to determine whether the Penn classification can predict hospital mortality in patients with acute Stanford type A and type B aortic dissections undergoing surgical or medical management. Design: Retrospective, observational study. Setting: Tertiary care, university hospital. Participants: Patients with acute aortic dissection between January 2008 and December 2017. Interventions: Examination of hospital mortality after surgical or medical management. Measurements and Main Results: Three hundred fifty-two patients had confirmed dissections (186 type A, 166 type B). The overall mortality was 18.8% for type A and 13.3% for type B. Penn class A patients with type A or type B dissections undergoing surgical repair had the lowest mortality (both 3.1%). Penn class B, C, or B+C patients with type A dissections and Penn class B+C patients with type B dissections undergoing medical management had the greatest incidence of mortality (50.0%-57.1%). All others had intermediate mortality (6.7%-39.3%). Logistic regression analysis demonstrated that Penn class B, C, and B+C patients had a greater odds of mortality and predicted mortality than did Penn class A patients. Conclusions: The Penn classification predicts hospital mortality in patients with acute Stanford type A or type B aortic dissections undergoing surgical or medical management. Early endovascular repair may confer lower risk of mortality in patients with type B dissections presenting without ischemia. Ó 2019 Elsevier Inc. All rights reserved. Key Words: aortic dissection; Stanford classification; Stanford type A; Stanford type B; Penn classification; hospital mortality
ACUTE AORTIC dissection can be life-threatening and often is associated with a high risk of early mortality. In 1965, DeBakey et al. reported improved outcomes after surgical repair based on the location and extent of the dissection.1 In 1970, the clinical experience from Stanford University Hospital indicated that mortality and prognosis for dissections involving the ascending aorta E. Sun has received funding (K08DA042314) from the National Institute on Drug Abuse, Rockville, MD, and consulting fees from Egalet Corporation, Wayne, PA, and the Mission LISA Foundation, Tampa, FL. * Address reprint requests to Albert T. Cheung, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Dr., H3578, Stanford, CA 94305. E-mail address: [email protected] (A.T. Cheung). https://doi.org/10.1053/j.jvca.2019.08.036 1053-0770/Ó 2019 Elsevier Inc. All rights reserved.
were distinct from dissections limited to the descending aorta.2 The initial experience from the International Registry for Aortic Dissection confirmed that patients with Stanford type A dissections involving the ascending aorta had improved survival in response to surgical repair.3 In contrast, patients with Stanford type B dissections limited to the descending aorta had improved survival in response to medical therapy. For this reason, the Stanford classification, based on the anatomic location and extent of the dissection, serves as a useful guide to determine whether patients should be treated emergently with surgical repair or conservatively with medical management.2 Despite this approach, there remains substantial variability in hospital mortality among patients appropriately treated for type A or type B aortic dissections.2,3
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To address the differences in mortality among patients undergoing surgical treatment for type A dissections, the Penn classification was developed to stratify patients based on their ischemic pattern or pathophysiologic condition at time of presentation.4,5 The Penn classification improved outcome prediction among this group of patients based on the presence or absence of branch-vessel malperfusion, circulatory collapse, or both.4 Only a small number of international studies have validated the utility of the Penn classification to predict mortality in patients with type A dissections undergoing surgical repair.6-9 Furthermore, the utility of the Penn classification for stratifying hospital mortality risk in patients with type B dissections is unclear despite some evidence that ischemic complications also have a prognostic effect in this condition.10 The recent development of endovascular repair techniques for type B dissections and expanded range of surgical repairs that can be performed in current practice make it important to subclassify patients into low- and high-risk groups for more nuanced clinical decision making.11-13 Thus, the aim of the present study was to determine whether the Penn classification could be used to stratify hospital mortality risk in patients with either acute Stanford type A or type B aortic dissections undergoing either surgical or medical management. The secondary objective was to identify additional risk factors for hospital mortality in the contemporary management of acute aortic dissection. Methods Patient Identification With Institutional Review Board approval, a single-center retrospective investigation was performed. All patients admitted or transferred to the authors’ tertiary care, university-affiliated hospital with a diagnosis of possible acute aortic dissection from January 2008 to December 2017 were identified from the institutional database. After manual chart review, patients were ultimately included if they had a new diagnosis of acute aortic dissection documented in the electronic medical record (EMR) based on clinical findings (eg, sudden onset of sharp or tearing chest, thoracic or abdominal pain, pulse or blood pressure discrepancy between right and left arm) and new imaging evidence of an aortic dissection flap separating the false lumen from the true lumen, intramural hematoma or entry tear, or penetrating ulcer on computed tomography or transesophageal echocardiography.14-17 Patients with an incorrect diagnosis or with no radiographic confirmation of acute aortic dissection were excluded from the final analysis. Patients with known or preexisting aortic dissections before the index hospitalization (noted in the EMR or with evidence on prior imaging studies) were classified as having a chronic dissection and also were excluded. Data Abstraction and Definitions Data were reviewed and collected by 3 authors (M.T., N. M.A., J.Z.), and 5 of the authors were involved in data analysis (M.T., A.K., N.M.A., E.S., A.T.C.). In addition to obtaining
data contained within the institutional database, the EMR of each patient was reviewed manually to collect data on baseline patient characteristics, preexisting comorbidities, whether the dissection was treated medically or surgically, hospital course, complications, and hospital mortality. All aortic dissections were classified as Stanford type A if they involved the ascending aorta and Stanford type B if the involvement was limited to the descending aorta. Medical management was defined as nonsurgical treatment with medications exclusively during the course of the hospitalization. Surgical management was defined as surgical treatment by open or endovascular repair during the index hospitalization. All patients were stratified based on their condition at the time of presentation according to the Penn classification as follows: Penn class A indicating the absence of malperfusion or circulatory collapse, Penn class B indicating the presence of branch-vessel malperfusion, Penn class C indicating the presence of circulatory collapse, and Penn class B+C indicating the presence of both branch-vessel malperfusion and circulatory collapse.4 The criteria used to define branch-vessel malperfusion (Penn class B) were the presence of any of the following: stroke; paraplegia; new-onset lower extremity weakness or paralysis; upper or lower extremity pulse deficits; need for vascular surgery to restore blood flow to the extremities; acute kidney injury (AKI), defined as serum creatinine greater than 2 times the baseline, glomerular filtration rate reduction by more than 50% at time of admission, urine output less than 0.5 mg/kg/h in the first 12 hours, or new need for renal replacement therapy; mesenteric ischemia, malperfusion to the celiac trunk, superior mesenteric artery, or inferior mesenteric artery with either radiographic evidence or clinical findings of an acute abdomen; need for emergency bowel resection; or acute gastrointestinal bleeding resulting from ischemic colitis (Table 1). The criteria used to define circulatory collapse (Penn class C) were the presence of any of the following: newly reduced left ventricular ejection fraction less than 50%, new right ventricular dysfunction, pericardial tamponade, acute coronary ischemia, myocardial infarction, or need for intra-aortic balloon pump or venoarterial extracorporeal membrane oxygenation support (see Table 1). The criteria for Penn class B+C were defined as patients who presented with at least 1 criterion for both Penn class B and class C. Criteria for Penn class A were defined as patients without any of the conditions associated with Penn class B or class C at the time of presentation. Statistical Analysis All statistical analyses were conducted in consultation with a statistician (E.S.). The primary objective was to determine whether the Penn classification predicts hospital mortality in patients with either acute Stanford type A or type B aortic dissection undergoing either medical or surgical management. Observed mortality rates in the patient population are reported along with 95% confidence intervals (CIs) estimating the binomial approximation of the true proportion. The secondary objective was to identify other risk factors (related to branch-vessel
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Table 1 Criteria Used for Penn Classification System Penn Classification
Criteria
Penn class A Penn class B
Absence of malperfusion (class B) or circulatory collapse (class C) Branch-vessel malperfusion: ▪ Stroke ▪ Paraplegia ▪ New-onset lower extremity weakness or paralysis ▪ Upper or lower extremity pulse deficits
Penn class C
▪ Need for vascular surgery to restore blood flow to the extremities ▪ Acute kidney injury, defined as serum creatinine greater than 2 times baseline, glomerular filtration rate reduction by more than 50%, urine output less than 0.5 mg/kg/h in the first 12 h, or new need for renal replacement therapy ▪ Mesenteric ischemia; malperfusion to the celiac trunk, superior mesenteric artery, or inferior mesenteric artery with either radiographic evidence or clinical findings of an acute abdomen; need for emergency bowel resection; or acute gastrointestinal bleeding owing to ischemic colitis Circulatory collapse: ▪ Newly reduced left ventricular ejection fraction <50% ▪ New right ventricular dysfunction ▪ Pericardial tamponade ▪ Acute coronary ischemia ▪ Myocardial infarction ▪ Need for intra-aortic balloon pump
Penn class B + C
▪ Need for venoarterial extracorporeal membrane oxygenation Meeting at least 1 criterion for malperfusion (class B) and circulatory collapse (class C)
malperfusion, circulatory collapse, or unrelated to ischemic complications) associated with hospital mortality in acute aortic dissections. Logistic regression analysis was used to determine the odds ratio (OR) and 95% CI for hospital mortality and predicted mortality for each Penn class, adjusting for Stanford classification and whether patients were treated with surgery. Differences in mortality rate as a function of calendar time were assessed using logistic regression analysis. For patients who died, one-way analysis of variance was used to assess for differences in mean time to death among Penn classes. Chi-square tests and univariate analyses were used to test the significance of risk factors predicting hospital mortality. All data were analyzed using STATA statistical software, Version 14.0 (StataCorp, LLC, College Station, TX). In all cases, 2-tailed p values < 0.05 were considered to be statistically significant.
For patients who died, the mean (§ standard deviation) time to death with type A dissections was 2.4 § 2.1 days for Penn class A, 12.4 § 19.3 days for Penn class B, 3.7 § 4.0 days for Penn class C, and 11.2 § 9.4 days for Penn class B+C (p = 0.27). The mean time to death for patients with type B dissection was 4.1 § 5.4 days for Penn class A, 7.9 § 8.4 days for Penn class B, and 7.0 § 4.4 days for Penn class B+C (p = 0.52). There was no significant trend or differences in hospital mortality rates over calendar time over the 10-year study period, as stratified by type A overall (p = 0.25), type A with
Results A total of 508 patients were initially identified from the authors’ database as being admitted with possible acute aortic dissection between January 2008 and December 2017. Among the 508 patients, 156 were excluded because of an incorrect diagnosis (n = 47), chronic dissection (n = 19), or inability to confirm the diagnosis of acute aortic dissection based on manual review of imaging studies (n = 90). A total of 352 patients, 186 with acute Stanford type A and 166 acute type B aortic dissections were included in the final analysis (Fig 1). The summary statistics of the patient population are displayed in Table 2. The overall hospital mortality was 18.8% (95% CI 13.5%-25.2%) for patients with type A dissections and 13.3% (95% CI 8.5%-19.4%) for patients with type B dissections (Table 3).
Fig 1. Flow diagram of patient selection and exclusion criteria.
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Table 2 Summary Statistics for Patients With Acute Aortic Dissection Between January 2008 and December 2017
Mean age (y) Male Female Diabetes mellitus Chronic kidney disease Penn class A Penn class B Penn class C Penn class B+C Medical management Surgical management Hospital mortality
Stanford Type A (n = 186)
Stanford type B (n = 166)
All (n = 352)
62.9 (15.6) 123 (66.1%) 63 (33.9%) 7 (3.8%) 24 (12.9%)
58.9 (15.3) 114 (68.7%) 52 (31.3%) 9 (5.4%) 13 (7.8%)
61.0 (15.6) 237 (67.3%) 115 (32.7%) 16 (4.5%) 37 (10.5%)
81 (43.5%) 56 (30.1%) 19 (10.2%) 30 (16.1%) 29 (15.6%)
114 (68.7%) 42 (25.3%) 4 (2.4%) 6 (3.6%) 100 (60.2%)
195 (55.4%) 98 (27.8%) 23 (6.5%) 36 (10.2%) 129 (36.6%)
157 (84.4%)
66 (39.8%)
223 (63.3%)
35 (18.8%)
22 (13.3%)
57 (16.2%)
NOTE. Data are reported as mean and standard deviation or as n and percent. Stanford Type A is defined as aortic dissection involving the ascending aorta. Stanford Type B is defined as aortic dissection confined to the descending aorta. Penn class A, the absence of branch-vessel malperfusion and circulatory collapse. Penn class B, branch-vessel malperfusion. Penn class C, circulatory collapse. Penn class B+C, both branch-vessel malperfusion and circulatory collapse.
surgical management (p = 0.56), type B overall (p = 0.49), and type B with surgical management (p = 0.42). Of all patients in this study, 44.6% (157/352) experienced associated complications and were classified as Penn class B, C, or B+C. The remaining 55.4% (195/352) of patients experienced no acute complications at the time of presentation and were classified as Penn class A. The lowest hospital mortality rate was observed among Penn class A patients undergoing surgical repair for type A dissections (3.1% [95% CI 0.4%10.7%]) and type B dissections (3.1% [95% CI 0.1%-16.2%]). The highest hospital mortality rates were observed among medically managed patients with type A dissections in Penn class B (57.1% [95% CI 18.4%-90.1%]), class C (50.0% [95% CI 6.8%-93.2%]), or class B+C (50.0% [95% CI 1.3%98.7%]) and in medically managed patients with type B dissections in Penn class B+C (50.0% [95% CI 1.3%-98.7%]) (see
Table 3). All other patients had intermediate hospital mortality rates in the range of 6.7% (95% CI 0.2%-31.9%) to 39.3% (95% CI 21.5%-59.4%) (see Table 3). Logistic regression analysis, adjusted for whether or not patients had surgical repair, demonstrated that for all aortic dissections, Penn class B (OR 7.9, 95% CI 3.6-17.4; p < 0.001) and Penn class B+C (OR 14.2, 95% CI 5.4-37.7; p < 0.001) were associated with higher odds of hospital mortality compared with Penn class A (Table 4). For all dissections, Penn class C patients had higher odds of mortality compared with patients with Penn class A, but the difference was not quite statistically significant (OR 3.1, 95% CI 0.8-12.3; p = 0.111). Among patients with type A dissections, Penn class B (OR 5.6, 95% CI 1.9-16.4; p = 0.002) and Penn class B+C patients (OR 10.1, 95% CI 3.2-32.4; p < 0.001) had greater odds of hospital mortality compared with Penn class A patients (see Table 4). Similarly, among patients with type B dissections, Penn class B (OR 6.9, 95% CI 2.5-18.7; p < 0.001) and Penn class B+C (OR 7.6, 95% CI 1.2-49.2; p = 0.032) patients had greater odds of mortality compared with patients in Penn class A (see Table 4). Predicted mortality rates by Stanford type and Penn classifications of the study population are shown in Table 5. The predicted mortality rates for Penn class A dissections were 5.2% (95% CI 2.1%-8.3%) overall, 6.2% (95% CI 0.9%-11.4%) for type A dissections, and 6.1% (95% CI 1.7%-10.5%) for type B dissections. The predicted mortality rates for Penn class B dissections were 30.3% (95% CI 20.8%-39.8%) overall, 26.8% (95% CI 15.2%-38.4%) for type A dissections, and 30.9% (95% CI 17.0%-44.9%) for type B dissections. The predicted mortality rates for Penn class C dissections were 14.4% (95% CI 0.0%-29.6%) overall, 15.8% (95% CI 0.0%-32.2%) for type A dissections, and indeterminate for type B dissections (there were no deaths in the group of patients with Penn class C, type B aortic dissections to generate a statistical estimate). The predicted mortality rates for Penn class B+C dissections were 43.8% (95% CI 26.6%-60.9%) overall, 40.0% (95% CI 22.5%-57.5%) for type A dissections, and 33.3% (95% CI 0.0%-71.1%) for type B dissections. In addition to the Penn classification, the following univariate risk factors were associated with a greater risk of mortality
Table 3 Hospital Mortality Among Patients Admitted With Acute Aortic Dissection Between January 2008 and December 2017 According to Stanford Type, Medical Versus Surgical Management, and Penn Classification
Stanford type A Overall Medical Surgical Stanford type B Overall Medical Surgical
All
Penn A
Penn B
Penn C
Penn B + C
35/186 (18.8%) 10/29 (34.4%) 25/157 (15.9%)
5/81 (6.2%) 3/16 (18.8%) 2/65 (3.1%)
15/56 (26.8%) 4/7 (57.1%) 11/49 (22.4%)
3/19 (15.8%) 2/4 (50.0%) 1/15 (6.7%)
12/30 (40.0%) 1/2 (50.0%) 11/28 (39.3%)
13/42 (30.9%) 4/16 (25.0%) 9/26 (34.6%)
0/4 (0.0%) 0/0 (n/a) 0/4 (0.0%)
22/166 (13.3%) 11/100 (11.0%) 11/66 (16.7%)
7/114 (6.1%) 6/82 (7.3%) 1/32 (3.1%)
2/6 (33.3%) 1/2 (50.0%) 1/4 (25.0%)
NOTE. Data are reported as mean and standard deviation or as n and percent. Stanford Type A is defined as aortic dissection involving the ascending aorta. Stanford Type B is defined as aortic dissection confined to the descending aorta. Penn class A, the absence of branch-vessel malperfusion and circulatory collapse. Penn class B, branch-vessel malperfusion. Penn class C, circulatory collapse. Penn class B+C, both branch-vessel malperfusion and circulatory collapse.
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Table 4 Logistic Regression Analysis for Hospital Mortality by Stanford Type and Penn Classification Using Penn Class A as the Reference Group Penn B
Overall Stanford Type A Stanford Type B
Penn C
Penn B + C
OR (95% CI)
p Value
OR (95% CI)
p Value
OR (95% CI)
p Value
7.9 (3.6-17.4) 5.6 (1.9-16.4) 6.9 (2.5-18.7)
<0.001 0.002 <0.001
3.1 (0.8-12.3) 2.9 (0.6-13.2) Omitted*
0.111 0.180 Omitted*
14.2 (5.4-37.7) 10.1 (3.2-32.4) 7.6 (1.2-49.2)
<0.001 <0.001 0.032
NOTE. Data are reported as odds ratios (OR) and 95% confidence interval (95% CI). Stanford Type A is defined as aortic dissection involving the ascending aorta. Stanford Type B is defined as aortic dissection confined to the descending aorta. Penn class A, the absence of branch-vessel malperfusion and circulatory collapse. Penn class B, branch-vessel malperfusion. Penn class C, circulatory collapse. Penn class B+C, both branch-vessel malperfusion and circulatory collapse. * No deaths encountered in Penn class C, Stanford type B, thus the logistic regression omitted this group from the analysis.
Table 5 Predicted Mortality by Stanford Type and Penn Classification Penn A
Overall Stanford type A Stanford type B
Penn B
Penn C
Penn B + C
Predicted Mortality (95% CI)
SE
Predicted Mortality (95% CI)
SE
Predicted Mortality (95% CI)
SE
Predicted Mortality (95% CI)
SE
5.2% (2.1%-8.3%) 6.2% (0.9%-11.4%) 6.1% (1.7%-10.5%)
1.6% 2.7% 2.2%
30.3% (20.8%-39.8%) 26.8% (15.2%-38.4%) 30.9% (17.0%-44.9%)
4.8% 5.9% 7.1%
14.4% (0.0%-29.6%) 15.8% (0.0%-32.2%) Omitted*
7.7% 8.4% Omitted*
43.8% (26.6%-60.9%) 40.0% (22.5%-57.5%) 33.3% (0.0%-71.1%)
8.8% 8.9% 19.2%
NOTE. Data are reported as predicted mortality (%) and 95% confidence interval (95% CI). Stanford Type A is defined as aortic dissection involving the ascending aorta. Stanford Type B is defined as aortic dissection confined to the descending aorta. Penn class A, the absence of branch-vessel malperfusion and circulatory collapse. Penn class B, branch-vessel malperfusion. Penn class C, circulatory collapse. Penn class B+C, both branch-vessel malperfusion and circulatory collapse. Abbreviation: SE, standard error. * No deaths encountered in Penn class C, Stanford type B, thus the logistic regression omitted this group from the analysis.
for all acute dissections: older age (mean age 70.2 v 61.2; p < 0.001), AKI (p = 0.040), lactic acidosis (p < 0.001), mesenteric ischemia (p < 0.001), stroke (p < 0.001), pericardial tamponade (p = 0.026), myocardial ischemia (p = 0.018), cardiac arrest (p < 0.001), new-onset seizures (p < 0.001), and prolonged mechanical ventilation (p < 0.001). Female sex (p < 0.001) and medical management (p = 0.019) were associated with greater mortality for patients with type A dissections. There was no significant difference in mortality when comparing type of surgery performed (p = 0.87) and cerebral perfusion technique (p = 0.72) used to perform the surgeries. Discussion A large proportion of patients with acute aortic dissection present with various life-threatening complications that contribute to the variability in mortality associated with this condition. The present study demonstrates that the Penn classification is a valuable tool to predict hospital mortality among patients with Stanford type A or type B aortic dissections undergoing either surgical or medical management. The lowest mortality rates were found among Penn class A patients with type A and type B dissections undergoing surgical management and among the 44.6% of patients presenting with branch-vessel malperfusion, circulatory collapse, or both; the overall risk of mortality was increased by a factor of 7.9-fold, 3.1-fold, or 14.2-fold, respectively. Prior studies examining predictors of mortality in aortic dissections have reported on factors predominantly related to ischemic complications on presentation (eg, hypotension,
shock, mesenteric ischemia, AKI, limb ischemia, pulse deficit, myocardial ischemia or infarction).18-24 Augoustides et al. proposed classifying patients undergoing surgery for type A dissections based on the pattern of preoperative ischemia and reported hospital mortality rates of 3.1% for Penn class A, 25.6% for Penn class B, 17.6% for Penn class C, and 40.0% for Penn class B+C.4 Retrospective studies from Sweden, Japan, and Italy subsequently demonstrated similar results.6-9 The results of the present study are consistent with prior data and demonstrate similar effectiveness of the Penn classification in predicting mortality in patients with type B dissections. The findings in the present study support the general recommendation that surgical repair is the best option for patients with type A dissections and medical management is the best option for patients with type B dissections.2 However, application of the Penn classification provided additional insights into subtle differences in outcomes. For example, among the 29 patients with type A dissection treated medically, the survival rate for the 16 patients who were in Penn class A was 81.3% compared with the combined survival rate for the 13 patients who were in Penn class B, C, or B+C of only 46.2%. This finding suggests that medical management may be an acceptable option for patients with uncomplicated type A dissections for whom surgery may be too risky for other reasons (eg, advanced age, frailty, malignancy, dementia, hemorrhagic stroke). Another finding revealed by the Penn classification was that among the 114 patients with type B dissections in Penn class A, hospital mortality was lowest among those treated surgically (3.1%), a rate that was much lower than those treated
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medically (7.3%). Even though more data are needed, this finding suggests that early surgical or endovascular repair may confer a mortality benefit to a specific subset of patients with uncomplicated type B dissections. Thus, use of the Penn classification may lead to more nuanced clinical decision making regarding the potential risks and benefits of surgical versus medical management for both type A and type B dissections. Even though the patients in the present study were managed at a single hospital and no significant trends in mortality over time were observed, it is important to note that changes over the last decade in surgical technique and perioperative management may have influenced mortality rates that cannot be fully explained by the Stanford or Penn classification schemes. In fact, there are data to suggest that later year of surgery for patients with type A dissections was associated with decreased mortality.25 The absence of any significant trends in mortality in this study may be explained by the relatively limited number of patients with hospital mortality, a stable practice pattern within a single referral center, and the clinical availability of the full spectrum of endovascular repair techniques at the institution over the study period. Advancements in endovascular repair techniques for both type A and type B dissections have provided older, higher-risk patients a chance to benefit from surgical repair.11-13,26,27 It is possible that the improved survival seen among patients with uncomplicated type B dissections treated with surgery in the present study may be the consequence of these developments. Furthermore, the ideal management of aortic dissections complicated by malperfusion syndromes continues to evolve. Yang et al. reported reduced mortality with a staged repair consisting of upfront endovascular fenestration/stenting to establish reperfusion, followed by delayed open aortic repair for a subset of patients with relatively stable conditions.28,29 Leshnower et al. also reported survival benefits with similar staged repairs.30,31 These newer techniques have yet to be widely adopted and were not routinely used during the time of the present study. In addition, there has been a recent paradigm shift to manage patients with aortic dissections in a hybrid catheterization laboratory/operating room environment where the skill sets of cardiothoracic surgeons, interventional cardiologists, and cardiothoracic anesthesiologists can be integrated to simultaneously obtain hemodynamic control, perform noninvasive and invasive diagnostic studies, and provide immediate surgical or endovascular therapies all in a single clinical workspace while minimizing any delay.32,33 Even though the majority of patients in the present study with type B dissections undergoing endovascular repair were managed in a hybrid operating room, this approach was not routine for patients with type A dissections, who were mostly managed in a traditional operating room setting. The findings of this study should be interpreted in the context of its limitations as a retrospective observational study. Thus, the quality of the data is reliant on accuracy and completeness of the EMR and institutional database. In addition, stratification of patients into Penn classes was based on manual chart review rather than direct examination of patients. Finally, this study was conducted at a single referral center that specializes in the management of acute aortic dissection and the applicability of the findings to other clinical settings is unclear.
In conclusion, the Penn classification is useful in predicting mortality in patients with type A and type B dissections undergoing medical or surgical management and allows for more nuanced clinical decision making. The authors found that surgery was generally the best option for patients with type A dissections, but the survival rate among a small subset of patients with uncomplicated type A dissections managed medically was acceptable. In addition, the mortality rate for patients with complicated type B dissections was not significantly different among those treated medically or surgically. However, the mortality rate was lower among patients with uncomplicated type B dissections who were treated surgically compared with those treated medically. Additional studies are needed to confirm these findings before any changes to clinical practice can be recommended. Declaration of Competing Interest The authors report no financial interests nor conflicts of interest pertaining to the contents of this article. Dr. Eric C. Sun has an affiliation with the Department of Health Research and Policy, Stanford University School of Medicine. References 1 Debakey ME, Henly WS, Cooley DA, et al. Surgical management of dissecting aneurysms of the aorta. J Thorac Cardiovasc Surg 1965;49:130–49. 2 Daily PO, Trueblood HW, Stinson EB, et al. Management of acute aortic dissections. Ann Thorac Surg 1970;10:237–47. 3 Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): New insights into an old disease. JAMA 2000;283:897–903. 4 Augoustides JGT, Geirsson A, Szeto WY, et al. Observational study of mortality risk stratification by ischemic presentation in patients with acute type A aortic dissection: The Penn classification. Nat Clin Pract Cardiovasc Med 2009;6:140–6. 5 Augoustides JGT, Szeto WY, Desai ND, et al. Classification of acute type A dissection: Focus on clinical presentation and extent. Eur J Cardiothorac Surg 2011;39:519–22. 6 Olsson C, Hillebrant C-G, Liska J, et al. Mortality in acute type A aortic dissection: Validation of the Penn Classification. Ann. Thorac Surg 2011;92:1376–82. 7 Kimura N, Ohnuma T, Itoh S, et al. Utility of the Penn Classification in predicting outcomes of surgery for acute type A aortic dissection. Am J Cardiol 2014;113:724–30. 8 Danielsson E, Zindovic I, Bjursten H, et al. Generalized ischaemia in type A aortic dissections predicts early surgical outcomes only. Interact Cardiovasc Thorac Surg 2015;21:583–9. 9 Pisano C, Balistreri CR, Torretta F, et al. Penn classification in acute aortic dissection patients. Acta Cardiol 2016;71:235–40. 10 Augoustides JGT, Szeto WY, Woo EY, et al. The complications of uncomplicated acute type-B dissection: The introduction of the Penn classification. J Cardiothorac Vasc Anesth 2012;26:1139–44. 11 Alfson DB, Ham SW. Type B aortic dissections: Current guidelines for treatment. Cardiol Clin 2017;35:387–410. 12 Cooper M, Hicks C, Ratchford EV, et al. Diagnosis and treatment of uncomplicated type B aortic dissection. Vasc Med 2016;21:547–52. 13 Clough RE, Nienaber CA. Evidence for and risks of endovascular treatment of asymptomatic acute type B aortic dissection. J Cardiovasc Surg (Torino) 2017;58:270–7. 14 von Kodolitsch Y, Schwartz AG, Nienaber CA. Clinical prediction of acute aortic dissection. Arch Intern Med 2000;160:2977–82. 15 Kienzl D, Prosch H, T€opker M, et al. Imaging of non-cardiac, non-traumatic causes of acute chest pain. Eur J Radiol 2012;81:3669–74.
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24 Tolenaar JL, Froehlich W, Jonker FHW, et al. Predicting in-hospital mortality in acute type B aortic dissection: Evidence from International Registry of Acute Aortic Dissection. Circulation 2014;130:S45–50. 25 Geirsson A, Ahlsson A, Franco-Cereceda A, et al. Hospital volumes and later year of operation correlates with better outcomes in acute type A aortic dissection. Eur J Cardiothorac Surg 2018;53:276–81. 26 Kreibich M, Rylski B, Czerny M, et al. Influence of age and the burden of ischemic injury on the outcome of type A aortic dissection repair [E-pub ahead of print]. Ann Thorac Surg 2019 June 5. 27 Harky A, Chan JSK, Wong CHM, et al. Systematic review and meta-analysis of acute type B thoracic aortic dissection, open, or endovascular repair. J Vasc Surg 2019;69;1599-1609.e2. 28 Yang B, Rosati CM, Norton EL, et al. Endovascular fenestration/stenting first followed by delayed open aortic repair for acute type A aortic dissection with malperfusion syndrome. Circulation 2018;138:2091–103. 29 Yang B, Norton EL, Rosati CM, et al. Managing patients with acute type A aortic dissection and mesenteric malperfusion syndrome: A 20-year experience. J Thorac Cardiovasc Surg 2019;158:675–87. 30 Leshnower BG, Veeraswamy RK, Duwayri YM, et al. The “TEVAR-first” approach to DeBakey I aortic dissection with mesenteric malperfusion. Ann Thorac Surg 2014;97:693–6. 31 Leshnower BG, Keeling WB, Duwayri YM, et al. The “thoracic endovascular aortic repair-first” strategy for acute type A dissection with mesenteric malperfusion: Initial results compared with conventional algorithms [E-pub ahead of print]. J Thorac Cardiovasc Surg 2019 Feb 11. 32 Augoustides JGT, Patel PA, Savino JS, et al. The heart team approach to acute type A dissection: A new paradigm in the era of the integrated Penn classification and the Essen concept. Eur J Cardiothorac Surg 2013;43:404–5. 33 Tsagakis K, Konorza T, Dohle DS, et al. Hybrid operating room concept for combined diagnostics, intervention and surgery in acute type A dissection. Eur J Cardiothorac Surg 2013;43:397–404.