Long-Term Survival in Patients Presenting With Type A Acute Aortic Dissection
Insights from the International Registry of Acute Aortic Dissection (IRAD)
Background— Earlier studies evaluating long-term survival in type A acute aortic dissection (TA-AAD) have been restricted to a small number of patients in single center experiences. We used data from a contemporary, multi-center international registry of TA-AAD patients to better understand factors associated with long-term survival.
Methods and Results— We examined 303 consecutive patients with TA-AAD enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2003. We included patients who were discharged alive and had documented clinical follow-up data. Kaplan-Meier survival curves were constructed to depict cumulative survival in patients from date of hospital discharge. Stepwise Cox proportional hazards analysis was performed to identify independent predictors of follow-up mortality. We found that 273 (90.1%) patients had been managed surgically and 30 (9.9%) were managed medically. Patients who were dead at follow-up were more likely to be older (63.9 versus 58.4 years, P=0.007) and to have had previous cardiac surgery (23.9% versus 10.6%, P=0.01). Survival for patients treated with surgery was 96.1%±2.4% and 90.5%±3.9% at 1 and 3 years versus 88.6%±12.2% and 68.7%±19.8% without surgery (mean follow-up overall, 2.8 years, log rank P=0.009). Multivariate analysis identified a history of atherosclerosis (relative risk (RR), 2.17; 95% confidence interval [CI], 1.08 to 4.37; P=0.03) and previous cardiac surgery (RR, 2.54; 95% CI, 1.16 to 5.57; P=0.02) as significant, independent predictors of follow-up mortality.
Conclusions— Contemporary 1- and 3-year survival in patients with TA-AAD treated surgically are excellent. Independent predictors of survival during the follow-up period do not appear to be influenced by in-hospital risks but rather preexisting comorbidities.
Short-term and long-term survival rates after acute type A aortic dissection (TA-AAD) are unknown. Previous studies have reported survival rates between 52% and 94% at 1 year and between 45% and 88% at 5 years.1–5 However, most of these studies were single-center experiences and often included type A and type B dissections, as well as patients presenting with acute and chronic dissections. Further, most had enrollment periods spanning decades. The International Registry of Acute Aortic Dissection (IRAD) represents 21 large referral centers from around the world with consecutively enrolled patients presenting with TA-AAD. It includes clinical information on in-hospital clinical outcomes and follow-up data. The purpose of this study was to evaluate long-term survival rates in TA-AAD after hospital discharge. Additionally, we report clinical differences in patients who survived during the follow-up period versus those who died.
Materials and Methods
The IRAD is a multinational registry of 21 referral centers in 11 countries designed to provide an unbiased representative population of patients with acute aortic dissection. Treatment during the index hospitalization or in follow-up was not standardized but at the discretion of each patient’s treating physician. Full details of the IRAD methods have been previously published.6,7 The authors had full access to the data and take full responsibility for their integrity. All authors have read and agree to the manuscript as written.
We examined data on all patients with TA-AAD enrolled in IRAD between January 1, 1996 and December 31, 2003. TA-AAD was defined as any nontraumatic dissection involving the ascending aorta presenting within 14 days of symptom onset.8,9 Patients were identified prospectively at presentation or retrospectively via discharge diagnoses, imaging, and surgical databases. Diagnosis was based on imaging, surgical visualization, or on autopsy.
Of the 1417 patients enrolled in IRAD with acute aortic dissection, 885 (62.5%) had type A aortic dissections. Our study evaluated only those 617 (69.7%) who were discharged from the hospital alive. To minimize follow-up bias, our study included 329 (53.3%) patients from the 8 of 15 referral centers with >80% follow-up. Of these, 303 (92.1%) had follow-up death data that made up our study population. Median follow-up time was 2.8 years (Figure 1).
Clinical variables were recorded on a standardized form that included information on patient demographics, history, clinical presentations, physical findings, imaging study results, details of medical and surgical treatment, and patient outcomes including mortality. Data forms were reviewed for internal consistency and validity and then scanned electronically into an Access database.
Yearly follow-up data were obtained up to 5 years after discharge using standardized forms. Collected data included variables on clinical, imaging, and vital information. When applicable, additional data on mortality was obtained through the Social Security Death Index. At each enrolling hospital, study investigators obtained approval from their ethics or institutional review board to participate in IRAD and its follow-up study.
We compared patients who had died during follow-up to those who were alive. Summary statistics between the 2 groups are presented as frequencies for categorical variables and mean±standard deviation for continuous variables. In all cases, missing data were not defaulted to negative, and denominators reflect only cases reported. Univariate associations with death among clinical variables were obtained using χ2 and/or 2-sided Fisher exact tests and Student t tests. Stepwise Cox proportional hazards analysis was performed to identify independent predictors of follow-up mortality. Initial modeling used variables marginally suggestive of an unadjusted association to follow-up mortality (P<0.20). Variables were reviewed for clinical significance before testing. Ascending stepwise selection of variables after controlling for gender and age was performed sequentially with a default value for inclusion set at P<0.05. SAS Version 8.2 (SAS Institute) was used for all analyses.
Study Population and Baseline Characteristics
The mean age was 59.3±13.2 years (Table 1) with the majority being men (72.6%); 73 (24.1%) were older than age 70 and 213 (72.0%) had a history of hypertension. Atherosclerosis (24.8%) and a history of previous cardiovascular surgery (12.7%) were not uncommon.
In-Hospital Management and Outcomes
A total of 273 (90.1%) patients received surgery for the repair of their TA-AAD and 30 (9.9%) were managed medically. The reason for medical treatment was documented in 68% of cases. Of those, age and/or comorbid illness precluded surgical management in 68% of patients. Patient refusal was cited as the reason in 18% of cases.
All cause mortality at anytime during the 5-year follow-up period occurred in 16.2% (49/303) of patients with a mean survival of 2.4 years (Figure 2). Patients from centers with <80% follow-up had similar mortality rates to those with >80% follow-up (16.8% versus 16.2%, P=0.87). Those patients managed surgically had a significantly lower follow-up mortality of 13.9% (38/273, mean survival 2.5 years) versus 36.7% (11/30, mean survival 2.1 years, P<0.01) for those managed medically.
Figure 3 shows the survival curves estimated by the Kaplan-Meier method stratified by in-hospital management. The unadjusted survival rate at 1 year was 96.1%±2.4% and 88.6%±12.2% for surgery versus medical treatment, respectively, with further separation of the curves at 3 years with survival rates of 90.5% ± 3.9 and 68.7% ±19.8 (median 2.8 years, log rank P=0.009).
Univariate Predictors of Follow-up Death for All Patients With Type A Aortic Dissection.
Patients who died during the entire follow-up period were significantly more likely to be older (Table 1), have a history of atherosclerosis, and were 2.3-fold more likely to have had previous cardiovascular surgery. Typical presentation with chest or back pain occurred slightly less frequently in the patients who died at follow-up (Table 2). Findings on in-hospital chest x-ray or ECG did not differ between groups. Based on in-hospital imaging including computed tomography, magnetic resonance imaging, or transesophageal echo, patients who died during the follow-up period were significantly less likely to have had aortic regurgitation
Patients who survived the follow-up period were much more likely to have received surgery to treat their type A dissection versus medicines alone (92.5% versus 7.5%, P<0.01) (Table 3). Operative variables did not differ between the patients who survived the follow-up period versus those who died. Analysis of in-hospital complications showed that acute renal failure was the only in-hospital complication associated with an increased likelihood of follow-up death irrespective of surgical or medical therapy (P=0.04) (Table 4).
At discharge from the initial hospitalization, the mean systolic blood pressure was significantly higher (129.6±15.3 versus 122.4±14.7, P<0.01) in patients who eventually died during the follow-up period without any differences in diastolic blood pressure (Table 5). Antihypertensive medication at discharge was used frequently in all patients. When comparing medication usage at discharge between patients who survived the follow-up period to those who died, vasodilators were used more frequently in those patients who died (32.6% versus 17.3%, P=0.02) (Table 5).
Independent Predictors of Follow-Up Mortality
Age (≥70 years old) and gender-adjusted Cox proportional hazards analysis identified a history of atherosclerosis (relative risk [RR], 2.17; 95% confidence interval [CI], 1.08 to 4.37; P=0.03) and a history of previous cardiac surgery (RR, 2.54; 95% CI, 1.16 to 5.57; P=0.02) as the only significant independent predictors of follow-up mortality (Table 6).
Follow-Up Mortality Rates in Patients With Type A Acute Aortic Dissection
Our registry provides a unique opportunity to evaluate long term mortality rates in patients with TA-AAD from 8 tertiary referral centers enrolled between 1996 and 2003. This relatively short time span of enrollment minimizes the impact of changing strategies in aortic dissection care such as surgical methods, anesthesia, cardiopulmonary support, and intensive care unit care as well as follow-up issues including the use of advanced imaging for surveillance in these patients after they survived to hospital discharge.
Previous work in IRAD has already shown the in-hospital mortality rate of TA-AAD patients to be 26.9% when subjected to timely and successful surgery to the ascending aorta versus 56.2% in those treated medically without any surgery.10 These numbers reflect the contemporary “real-world” literature. The existing literature regarding follow-up outcomes in patients after discharge from the hospital is less well-established.
In our study, the 1- and 3-year survival in the surgically treated cohort surviving to hospital discharge is 96.1%±2.4% and 90.5%±3.9%, respectively. These numbers are excellent and reflect the successful and timely repair of the ascending aorta. A comparison to the existing literature is difficult because the majority of the literature begins their survival analysis on hospital day 1 thereby including in-hospital deaths.2,3,5,11,12 In contrast, few published reports such as ours begin their survival analysis on the day of discharge.3 A recent report by Chiappini et al reported on post-discharge survival rates of 94.8±1.2 at 5 years and 88.1±2.6 at 10 years in 487 patients enrolled at 2 centers over 27 years. By extrapolation their excellent findings corroborate results in IRAD reported here.
Medically treated patients with TA-AAD have extremely high in-hospital mortality rates exceeding 50%.7,10 However, very little has been published regarding the fate of these patients once they survive to hospital discharge. Contrary to their in hospital trajectory, our analysis found that the patients who survive to hospital discharge have a 1- and 3-year survival of 88.6%±12.2 and 68.7%±19.8, respectively.13 Two-thirds of patients who survive the index hospitalization without surgical correction were alive at 3 years. This is in contrast to the <20% survival at 1 year in the medically treated patients reported by Chirillo et al.14 This contemporary perspective of the medically treated type A patients who survive to hospital discharge supports aggressive medical treatment and imaging surveillance among patients who for various reasons are not able to undergo surgery.
Many previous reports have elucidated independent predictors of in-hospital death such as age, visceral ischemia, hypotension, renal failure, tamponade, coma, pulse deficits, and malperfusion syndromes in general.2,3,10,15,16 Very few reports have determined independent predictors of long term follow-up mortality. In the most recent publication by Chiappini et al, they looked at 487 patients with TA-AAD from 2 centers over 27 years. Of the patients discharged from the hospital alive, only preoperative type II diabetes was a significant predictor of late death at follow up (P=0.008).3 Others have shown predictors of follow-up mortality to include Marfan syndrome, re-operation, stroke, cardiac failure, chronic renal dysfunction, and previous operation.1,9,11,16
Our study demonstrated that despite the many univariate demographic, clinical, and imaging covariates included in the model, only a history of atherosclerosis and a history of previous cardiac surgery were predictive of follow-up mortality. The in-hospital parameters that very accurately predicted in-hospital mortality in IRAD did not seem to influence follow-up mortality. This may reflect the behavior of the disease once the intimal tear has been resected and repaired. Most of the literature that provides information on long-term follow-up outcomes and cause-specific mortality has been fairly consistent with regards to the cause of death. Approximately 10% to 27% of deaths are related to the previously dissected aorta, which includes re-operation–related mortality, 35% to 60% are caused by cardiovascular causes such as myocardial infarction, congestive heart failure, and stroke. An additional 10% to 20% are unknown and 8% to 25% are sudden cardiac death.3,12,14,17 Therefore, at least 50% of death after discharge from the hospital may not be directly related to their repaired aorta but likely from other comorbid conditions.
Differences From Previous Studies
The differences between our study and previous investigations need to be emphasized. Previous surgical studies report on consecutively enrolled TA-AAD patients spanning 1 to 2 decades. Over this period, changes in perioperative anesthesia, surgical techniques, and follow-up care have occurred and therefore may not reflect contemporary care. However, contrary to the observation of the evolution of surgical techniques, Chiappini et al could not find the operative date over 27 years as a significant risk factor for operative death.3 Our study reflects only acute type A aortic dissections enrolled between 1996 and 2003 at 8 tertiary referral hospitals with a special interest in aortic diseases around the world. The short enrollment period minimizes variations in average survival making our survival analysis more applicable to care occurring right now.
Our study may not pertain to patients who are not treated at tertiary referral centers where the experience, volume, and logistics of IRAD centers may exceed average hospital performance and may not adequately represent all of IRAD because we only evaluated the 8 centers with >80% follow-up. Furthermore, we only had information on follow-up all-cause mortality and did not have information on cause of death. We were therefore unable to evaluate cause specific mortality or other end points such as freedom from re-operation, rupture or redissection. And finally, our follow-up did not study measures to qualitatively assess survival in these patients.
In conclusion, our study demonstrates excellent survival rates for TA-AAD in patients who survive to hospital discharge. Predictors of follow-up all cause mortality reflect patient history variables as opposed to in-hospital parameters or in-hospital complications, which may be explained by the successful in-hospital treatment of the acute dissection. Additionally, this study sheds some light on the medically treated cohort once they survive to hospital discharge. As opposed to a dismal in hospital prognosis, two-thirds of these patients are alive at 3 years if they survive the initial hospitalization. Thus, they deserve and probably benefit from ongoing medical therapy.
The International Registry of Acute Aortic Dissection (IRAD) Investigators
Kim A. Eagle, MD, University of Michigan, Ann Arbor, Michigan, USA; Eric M. Isselbacher, MD, Massachusetts General Hospital, Boston, Massachusetts, USA; Christoph A. Nienaber, MD, University of Rostock, Rostock, Germany.
Eduardo Bossone, MD, National Research Council, Lecce, Italy; Arturo Evangelista, MD, Hospital General Universitari Vall d’Hebron, Barcelona, Spain; Rossella Fattori, MD, University Hospital S. Orsola, Bologna, Italy; Dan Gilon, MD, Hadassah University Hospital, Jerusalem, Israel; Stuart Hutchison, MD, St. Michael’s Hospital, Toronto, Ontario, Canada; James L. Januzzi, MD, Massachusetts General Hospital, Boston, Massachusetts, USA; Alfredo Llovet, MD, Hospital Universitario “12 de Octubre,” Madrid, Spain; Debabrata Mukherjee, MD, University of Michigan, Ann Arbor, Michigan, USA; Truls Myrmel, MD, Tromsø University Hospital, Tromsø, Norway; Patrick O’Gara, MD, and Joshua Beckman, MD, Brigham and Women’s Hospital, Boston, Massachusetts, USA; Jae K. Oh, MD, Mayo Clinic, Rochester, Minnesota, USA; Linda A. Pape, MD, University of Massachusetts Hospital, Worcester, Massachusetts, USA; Udo Sechtem, MD, Robert-Bosch Krankenhaus, Stuttgart, Germany, Toru Suzuki, MD, University of Tokyo, Tokyo, Japan; Santi Trimarchi, MD, Instituto Policlinico San Donato, San Donato, Italy.
Data Management and Biostatistical Support
Jeanna V. Cooper, MS; Jianming Fang, MD; and Dean E. Smith, PhD, University of Michigan, Ann Arbor, Michigan, USA.
In-Hospital Covariates Assessed for Follow-Up Mortality
Age, gender, hypertension, atherosclerosis, bicuspid aortic valve, iatrogenic dissection, previous aneurysm, previous cardiovascular surgery, chest pain, syncope, congestive heart failure, aortic regurgitation, coronary artery compromise, surgery beyond 24 hours, and acute renal failure.
Sources of Funding
This work was supported by University of Michigan Faculty Group Practice and Varbedian Fund for Aortic Research. Thomas Tsai is supported by a training grant from the National Institutes of Health (#5T32HL007853–08).
Presented at the American Heart Association Scientific Sessions, Dallas, Tex, November 13–16, 2005.
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