Type A acute aortic dissection (TAAAD) is a life-threatening condition requiring emergent surgical intervention, often necessitating interfacility transfers.1,2 Establishing regional aortic networks is crucial for the proper triage and timely transfer of patients to facilities specialized for acute aortic dissection (AAD).3,4 Although the clinical benefits of interfacility transfer are unclear, the process must effectively balance the risk for clinical deterioration during transfer with potential delays in treatment. The differences in clinical presentation and outcomes between transferred and nontransferred patients with TAAAD are poorly defined. Therefore, the aim of this study was to assess the association between interfacility transfer and early mortality in patients with TAAAD using a Japanese multicenter registry database.
The Tokyo Acute Aortic Super-Network was established in 2011 to facilitate safe and efficient transfers for patients with AAD and has since maintained a prospective registry of patient-level data.5,6 The study protocol adhered to the ethical guidelines of the 1975 Declaration of Helsinki and the ethical guidelines for epidemiologic research of the Japanese government. This study was approved by the Institutional Review Board of the Tokyo CCU Network Scientific Committee.
We used data from 2,629 consecutive patients with TAAAD enrolled in our registry database between January 2015 and December 2018. The exclusion criteria were as follows: patients who were admitted >14 days after symptom onset or those with chronic aortic dissection (n = 15), patients with no available data on the symptom onset date (n = 42) and in-hospital outcomes (n = 55), patients who experienced cardiopulmonary arrest on arrival at the initial hospital (n = 190), and patients who were admitted >24 hours after symptom onset (n = 171). Of the remaining 2,156 patients, we classified individuals as either directly admitted (ie, not transferred) or admitted via interfacility transfer.
Inverse probability weighting (IPW) was used to account for baseline differences between nontransferred and transferred patients. All measured baseline variables were included in the logistic regression model with interfacility transfer as the dependent variable to calculate the propensity score for each patient. Stabilized weights were estimated by multiplying the marginal probability of interfacility transfer by the inverse of the probability of the actual designated group. After applying IPW, we compared 30-day mortality between the nontransferred and transferred groups across the entire cohort and in the subgroup of patients who underwent early surgical interventions within 72 hours of admission. To evaluate the association between interfacility transfer and 30-day mortality, a weighted logistic regression analysis was subsequently performed, incorporating additional outcome-related covariates (eg, age, sex, early surgical intervention, and major AAD-related complications), with robust SEs used to account for the weighting procedure. All statistical analyses were conducted using SPSS version 29 (IBM), with statistical significance set at a 2-sided P value of <0.05.
The baseline characteristics of the entire cohort are summarized in Table 1. Among the 2,156 patients (mean age 68 ± 14 years, 52.9% men), 1,145 (53.1%) underwent interfacility transfers, including 588 (27.3%) who were transferred from facilities lacking surgical capabilities. In the crude analysis, nontransferred patients were older than transferred patients. Transferred patients had a higher proportion of classic aortic dissection and were less likely to present with shock or hypotension (P < 0.001) and malperfusion (P = 0.05) at admission than nontransferred patients. Weekend admissions were observed more frequently among nontransferred patients. Transferred patients had longer median durations from symptom onset to hospital arrival (210 min vs 65 min; P < 0.001) and emergency surgery (325 min vs 283 min; P < 0.001) than nontransferred patients.
Table 1.
Baseline Characteristics of the Entire Cohort Before and After IPW
| Before IPW |
P Value | SMD | After IPW |
SMD | |||
|---|---|---|---|---|---|---|---|
| Nontransferred (n = 1,011) | Transferred (n = 1,145) | Nontransferred (n = 997.3) | Transferred (n = 1,161.1) | ||||
| Demographics | |||||||
| Age, y | 69.1 ± 14.2 | 67.4 ± 13.7 | 0.005 | 0.123 | 68.1 ± 14.3 | 68.4 ± 13.6 | 0.021 |
| Male | 546 (54.0) | 594 (51.9) | 0.323 | 0.043 | 524.0 (52.5) | 605.4 (52.1) | 0.008 |
| Comorbidities | |||||||
| Hypertension | 674 (66.7) | 788 (68.8) | 0.285 | 0.046 | 681.4 (68.3) | 787.5 (67.8) | 0.011 |
| Hyperlipidemia | 248 (24.5) | 299 (26.1) | 0.399 | 0.036 | 246.4 (24.7) | 292.1 (25.2) | 0.010 |
| Diabetes mellitus | 75 (7.4) | 98 (8.6) | 0.331 | 0.042 | 81.8 (8.2) | 97.7 (8.4) | 0.008 |
| Previous coronary artery disease | 40 (4.0) | 44 (3.8) | 0.892 | 0.006 | 39.4 (3.9) | 49.1 (4.2) | 0.014 |
| Previous stroke | 58 (5.7) | 94 (8.2) | 0.025 | 0.097 | 65.2 (6.5) | 79.0 (6.8) | 0.011 |
| Previous peripheral artery disease | 3 (0.3) | 11 (1.0) | 0.055 | 0.084 | 6.5 (0.7) | 7.6 (0.7) | <0.001 |
| History of heart failure admission | 31 (3.1) | 9 (0.8) | <0.001 | 0.166 | 18.2 (1.8) | 17.4 (1.5) | 0.025 |
| End-stage renal disease on HD | 16 (1.6) | 22 (1.9) | 0.624 | 0.026 | 18.4 (1.8) | 25.1 (2.2) | 0.022 |
| Presenting symptoms | |||||||
| Chest pain | 559 (55.3) | 637 (55.6) | 0.874 | 0.007 | 561.5 (56.3) | 644.0 (55.5) | 0.017 |
| Back pain | 360 (35.6) | 465 (40.6) | 0.017 | 0.103 | 389.2 (39.0) | 441.2 (38.0) | 0.021 |
| Abdominal pain | 62 (6.1) | 58 (5.1) | 0.281 | 0.046 | 59.2 (5.9) | 73.7 (6.3) | 0.017 |
| Dyspnea | 69 (6.8) | 50 (4.4) | 0.013 | 0.107 | 56.7 (5.7) | 70.5 (6.1) | 0.016 |
| Comatose/semicomatose | 83 (8.2) | 75 (6.6) | 0.140 | 0.064 | 72.1 (7.2) | 87.7 (7.6) | 0.012 |
| Shock/hypotension | 195 (19.3) | 130 (11.4) | <0.001 | 0.222 | 151.0 (15.1) | 176.4 (15.2) | 0.001 |
| Malperfusiona | 194 (19.2) | 183 (16.0) | 0.050 | 0.084 | 181.0 (18.2) | 204.2 (17.6) | 0.015 |
| Status of false lumen | 0.025 | 0.132 | 0.015 | ||||
| Classic aortic dissection | 632 (62.5) | 778 (67.9) | 655.6 (65.7) | 758.7 (65.3) | |||
| IMH | 214 (21.2) | 203 (17.7) | 191.6 (19.2) | 224.0 (19.3) | |||
| ULP type | 123 (12.2) | 110 (9.6) | 106.5 (10.7) | 124.3 (10.7) | |||
| Undetermined | 41 (4.2) | 54 (4.7) | 43.4 (4.4) | 54.0 (4.7) | |||
| DeBakey classification | 0.704 | 0.036 | 0.028 | ||||
| Type I | 825 (81.6) | 925 (80.8) | 813.0 (81.5) | 939.9 (81.0) | |||
| Type II | 169 (16.7) | 204 (17.8) | 167.2 (16.8) | 196.8 (17.0) | |||
| Undetermined | 17 (1.7) | 16 (1.4) | 17.1 (1.7) | 24.3 (2.1) | |||
| Hospital settings | |||||||
| Weekend admission | 319 (31.6) | 312 (27.2) | 0.028 | 0.095 | 297.2 (29.8) | 345.8 (29.8) | <0.001 |
| Emergency and critical care centers | 590 (58.4) | 514 (44.9) | <0.001 | 0.272 | 525.2 (52.7) | 614.8 (52.9) | 0.006 |
| High-volume aortic centersb | 452 (44.7) | 818 (71.4) | <0.001 | 0.563 | 575.1 (57.7) | 665.9 (57.4) | 0.006 |
Values are mean ± SD or n (%). A standardized mean difference of <0.1 represents acceptable balance.
HD = hemodialysis; IMH = intramural hematoma; IPW = inverse probability weighting; SMD = standardized mean difference; ULP = ulcerlike projection.
Malperfusion includes cerebral, myocardial, spiral, renal, mesenteric, and limb ischemia.
Aortic centers with annual case numbers of thoracic aortic surgery ≥46 (median).
Transferred patients were more likely to undergo surgical interventions, including surgical aortic repair and endovascular treatment, than nontransferred patients (90.1% vs 73.5%; P < 0.001). Thirty-day mortality was significantly lower among transferred patients than among nontransferred patients (8.5% vs 20.9%; P < 0.001). Furthermore, nontransferred patients had a higher incidence of aortic rupture (5.8% vs 3.3%; P = 0.007) than transferred patients. On the day of admission, 24 transferred patients (2.1%) and 69 nontransferred patients (6.8%) died before undergoing surgery.
After applying IPW, 30-day mortality was significantly lower among transferred patients than among nontransferred patients (10.6% vs 19.5%; P < 0.001). Weighted logistic regression analysis showed that interfacility transfer was significantly associated with lower 30-day mortality (OR: 0.60; 95% CI: 0.43-0.83; P = 0.002). Among patients undergoing early surgical intervention, IPW-adjusted 30-day mortality was lower in transferred patients than in nontransferred patients (8.0% vs 11.4%; P = 0.048).
The establishment of regional aortic networks are critical for improving care quality and outcomes for patients with TAAAD. Studies from non-Asian countries have shown significant reductions in 30-day mortality after implementing transfer systems that centralize care at high-volume centers with multidisciplinary expertise.7,8 Our previous report from Tokyo, Japan, indicated that surgical outcomes for TAAAD were favorable, with a 30-day mortality rate of 7.6%, despite a high rate of untreatable or inoperable cases.6 In the present study, the rate of surgical treatment was higher among transferred patients, potentially contributing to favorable outcomes. Conversely, a higher proportion of inoperable cases upon admission was observed among nontransferred group. The IPW-adjusted 30-day mortality rate was 8.0% in transferred patients with early surgical intervention, suggesting favorable surgical outcomes through efficient and safe interfacility transfer within our network.
There were some limitations to our study. First, the study was observational in nature; therefore, unmeasured confounders that affect mortality might have been present. Second, the registry captured all-comers cases of TAAAD in urban Tokyo; the generalizability of our findings to rural regions or countries with differing demographic profiles—such as variations in age distribution, socioeconomic status, and referral system accessibility or efficiency—remains uncertain.9 Third, potential selection bias must be considered; specifically, transferred patients may have been in a more stable condition, which could systematically affect outcome comparisons. Finally, although previous registry data have shown a strong inverse association between surgical mortality and surgeons’ experience in TAAAD,10 our data set lacked specific information on individual surgeons’ skill levels, which could independently influence surgical outcomes.
In conclusion, despite delays between symptom onset and surgery, interfacility transfer was not associated with adverse outcomes, supporting the importance of well-organized regional transfer systems and timely surgical intervention in the management of TAAAD.
Funding Support and Author Disclosures
Data collection and maintenance of the Tokyo CCU Network registry are financially supported by the Tokyo Metropolitan Government, which played no role in the execution of this study or the interpretation of the results. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Acknowledgments
The authors thank all members of the Tokyo CCU Network Scientific Committee, the Tokyo Fire Department, the Tokyo Medical Association, and the Bureau of Social Welfare of the Tokyo Metropolitan Government. The authors are grateful to Nobuko Yoshida and Kozue Murayama for their continuous and devoted contributions to managing the Tokyo CCU Network database.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
References
- 1.Pape L.A., Awais M., Woznicki E.M., et al. Presentation, diagnosis, and outcomes of acute aortic dissection: 17-year trends from the International Registry of Acute Aortic Dissection. J Am Coll Cardiol. 2015;66:350–358. doi: 10.1016/j.jacc.2015.05.029. [DOI] [PubMed] [Google Scholar]
- 2.Goldstone A.B., Chiu P., Baiocchi M., et al. Interfacility transfer of Medicare beneficiaries with acute type A aortic dissection and regionalization of care in the United States. Circulation. 2019;140:1239–1250. doi: 10.1161/CIRCULATIONAHA.118.038867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Harris K.M., Strauss C.E., Duval S., et al. Multidisciplinary standardized care for acute aortic dissection: design and initial outcomes of a regional care model. Circ Cardiovasc Qual Outcomes. 2010;3:424–430. doi: 10.1161/CIRCOUTCOMES.109.920140. [DOI] [PubMed] [Google Scholar]
- 4.Aggarwal B., Raymond C.E., Randhawa M.S., et al. Transfer metrics in patients with suspected acute aortic syndrome. Circ Cardiovasc Qual Outcomes. 2014;7:780–782. doi: 10.1161/CIRCOUTCOMES.114.000988. [DOI] [PubMed] [Google Scholar]
- 5.Takahashi T., Yoshino H., Akutsu K., et al. In-hospital mortality of patients with acute type A aortic dissection hospitalized on weekends versus weekdays. JACC Asia. 2022;2:369–381. doi: 10.1016/j.jacasi.2021.11.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ogino H., Yoshino H., Shimokawa T., et al. A new insight into superacute care for type A acute aortic dissection in the Tokyo Acute Aortic Super Network. J Thorac Cardiovasc Surg. 2024;167:41–51.e4. doi: 10.1016/j.jtcvs.2023.08.040. [DOI] [PubMed] [Google Scholar]
- 7.Vaja R., Talukder S., Norkunas M., et al. Impact of a streamlined rotational system for the management of acute aortic syndrome: sharing is caring. Eur J Cardiothorac Surg. 2019;55:984–989. doi: 10.1093/ejcts/ezy386. [DOI] [PubMed] [Google Scholar]
- 8.Maroto L.C., Ferrera C., Cobiella J., et al. Improvement of early outcomes in type A acute aortic syndrome after an Aorta Code implementation. Ann Thorac Surg. 2024;117:770–778. doi: 10.1016/j.athoracsur.2023.07.010. [DOI] [PubMed] [Google Scholar]
- 9.Nazir S., Ariss R.W., Minhas A.M.K., et al. Demographic and regional trends of mortality in patients with aortic dissection in the United States, 1999 to 2019. J Am Heart Assoc. 2022;11(7) doi: 10.1161/JAHA.121.024533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Benedetto U., Dimagli A., Kaura A., et al. Determinants of outcomes following surgery for type A acute aortic dissection: the UK National Adult Cardiac Surgical Audit. Eur Heart J. 2021;43:44–52. doi: 10.1093/eurheartj/ehab586. [DOI] [PMC free article] [PubMed] [Google Scholar]