Eur J Cardiothorac Surg 2004;25:683-690
© 2004 Elsevier Science NL
Late outcome of patients with aortic dissection: study of a national database
Hsi-Yu Yu,
Yih-Sharng Chen,
Shu-Chien Huang,
Shoei-Shen Wang,
Fang-Yue Lin*
Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7 Chung-Shan South Road, Taipei 100, Taiwan, ROC
Received 11 August 2003;
received in revised form 24 December 2003;
accepted 30 December 2003.
* Corresponding author. Address: Department of Surgery, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei 100, Taiwan, ROC. Tel.: +886-2-2312-3456x5073; fax: +886-2-2322-5697
e-mail: fylin1{at}ha.mc.ntu.edu.tw
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Abstract
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Objectives: The incidence of late mortality and morbidity of aortic dissection remained unchanged during the past 20 years. The present study was to analyze the risk factors of late events for patients with aortic dissection. Methods: A total of 5654 cases of aortic dissection (3871 males) were collected from the National Health Insurance Databases from 1996 to 2001. Age, gender, Marfan syndrome, and initial treatment modality were the main factors to be investigated. Corrective group was defined by surgical operation with cardiopulmonary bypass and palliative group for the remaining. Late aortic events were defined by late aneurysmal evolution of diseased aorta needing surgical intervention or death of aortic causes from 6 months to 6 years. Results: The incidence of aortic dissection was 43 per 1 000 000 population in our country. Corrective group accounted for 19.3% of them and palliative group for 80.7%. Marfan syndrome accounted for 1.5% of all cases (4.3% of corrective surgery group). The rate of freedom from mortality at 1, 6 months, and 6 years was 80.4±1.3, 69.0±1.5, and 56.5±2.9% for corrective group and 89.5±0.5, 78.4±0.6, and 46.1±1.35% for palliative group. Nearly half of the late mortalities were attributed to atherosclerosis-related conditions (cardiac, stroke, or aortic causes). The incidence of late aortic events was 2.48% per year on an average, comparable between corrective and palliative groups. This incidence increased since the fourth year after their initial episode. For corrective group, young age was a risk factor of late aortic events (relative risk of 0.60–0.82 per decade, P=0.037). For palliative group, Marfan syndrome and male gender were risk factors of late aortic events (relative risk of 4.08–10.7, P<0.001 in the former; relative risk of 1.46–2.1, P=0.002 in the latter). Conclusions: Late aortic events were not uncommon for both corrective and palliative groups, and its incidence increased since the fourth year after their initial episodes. Young age for corrective group, Marfan syndrome and male gender for palliative group were risk factors of late aortic events.
Key Words: Aortic dissection • Follow-up study • Surgery
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Introduction
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By the persistent endeavor to improve the acute management of aortic dissection [1–8], both in surgical technique and in end-organ protective strategy, the operative mortality of this disease has now achieved a low threshold below which it can hardly be reduced [9]. In contrast, the late outcome of these patients was less studied. The way to improve the overall outcome of this disease depends on how to reduce late mortality and late aortic aneurysmal evolution of the diseased aorta that is preventable by early intervention. The present study was to investigate the outcomes of aortic dissection by a National Health Database and to analyze the risk factors of late mortality and aortic events.
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1. Materials and methods
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Data in the present study was collected from National Health Insurance Database of our country (Taiwan, Republic of China) from 1996 to 2001. In Taiwan, less than 4% of the population was not covered by this insurance system, so the database was presumed to include over 96% of all hospital admission records (www.dgbas.gov.tw/dgbas03/bs3/report/N900409.htm). Cases of aortic dissection were defined by one of the five ICD-9 diagnostic codes as 4410*. Gathered parameters for every case were listed in Table 1. If more than one admission record existed for the same patient during the study period, only the first admission record was counted for the demographic analysis. Operative procedures were classified by the ICD-9 procedural codes in each admission record (up to five procedural codes for each admission record). Indication of surgical treatment was generally in accordance with published protocol [10–13]. Briefly, all Stanford type A aortic dissections were indicated for surgical management unless contraindicated; Stanford type B aortic dissections with substantial aortic dilation, shock, rupture, malperfusion, or intractable pain were indicated for surgery. Corrective group was defined by surgical operation with cardiopulmonary bypass and palliative group for the remaining.
Survival data was collected from National Mortality Database of the Department of Statistics, Ministry of Interior, Republic of China (Taiwan). Late aortic event was defined by the late aneurysmal evolution of diseased aorta to an extent needing surgical intervention or mortality of aortic causes.
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1.1. Statistical analyses
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Continuous data were expressed as means±SD. Time-related events were reported as annual attrition rates and plotted in Kaplan–Meier survival curve as well as hazard rate curve. Statistical comparisons between groups were calculated by Student's t-test, 
2 test, or log-rank test depending on the type of variables. Multivariate analysis of risk factors was conducted using logistic regression and Cox hazard regression analysis. For all statistical evaluation, data with P value less than 0.05 was considered significantly different between groups. All statistical works were performed with SPSS for Windows (SPSS Inc., IL).
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2. Results
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2.1. Age and gender distribution
A total of 5654 cases of aortic dissection between 1996 and 2001 (3871 males, 1783 females) were included in the present study, equal to an incidence of 43 per 1 000 000 population in our country. The incidence was higher in male gender and in old (Fig. 1)
. The average age of initial episode was 65.6±14.0 years, younger in corrective group than in palliative group (58.0±13.4 vs. 68.1±13.3 years, P<0.001). Eighty-four patients were also coded with Marfan syndrome, accounting for 1.5% of all cases of aortic dissection (4.3% in corrective group), with mean age of 37.5±11.2 years.
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Fig. 1. (A) Case number of aortic dissection in respective age and gender groups. (B) Incidence of aortic dissection in respective age and gender groups.
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2.2. Surgical procedures
Of the 5654 patients with aortic dissection, 1360 (24.1%) underwent surgical intervention. Among these patients, 1089 (19.3% of all) received surgery with cardiopulmonary bypass and were thus classified in corrective group. The remaining 4565 patients (80.7%) were in palliative group. In corrective group, surgical procedures included resection and grafting of the diseased aorta in 49%, grafting and aortic valvuloplasty (suspension) in 26%, grafting and aortic valve replacement (including Bentall's operation) in 21%, and grafting and coronary artery bypass grafting in 4%.
2.3. Thirty-day and 6-month mortality
The rate of 30-day mortality in corrective group was higher than that in palliative group (19.6±1.3 vs. 10.5±0.5%, P<0.01; Fig. 2)
. The hazard of mortality decreased rapidly since the first month after their initial presentation to reach a stable rate at 6 months for both corrective and palliative groups. Freedom from mortality at 6 months was 69.0±1.5% for corrective group and 78.4±0.6% for palliative group. Old age and male gender were risk factors of 6 months' mortality for corrective group (Table 2), while old age, male gender, and Marfan syndrome were risk factors of 6 months' mortality for palliative group.
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Fig. 2. Kaplan–Meier survival curve for all aortic dissection cases, grouped by treatment mode, and compared to that of age- and sex-matched group.
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2.4. Late mortality
Freedom from mortality was 56.5±2.9% at 6 years for corrective group (Fig. 2), equal to an annual attrition rate of 2.3% per year between the period of 6 months and 6 years, comparable to their age- and sex-matched group (2.3% per year). Freedom from mortality was 46.1±1.3% for palliative group at 6 years, equal to an annual attrition rate of 5.8% per year, higher than their age- and sex-matched group (3.7% per year). Aortic cause, cardiac cause, and stroke accounted for 29, 16, 16% of all late mortality, respectively, for corrective group, and 16, 20, 12%, respectively, for palliative group (Fig. 3)
. All these three causes accounted for a total of 61 and 48% of late mortality for respective groups. In multivariate analysis for the risk factors of late mortality, only old age was associated with high late mortality for either group (P=0.052 for corrective group and P<0.001 for palliative group; Table 2). Neither male gender nor Marfan syndrome was associated with higher late mortality (for male gender, P=0.822 and 0.356 for corrective and palliative group, respectively; for Marfan syndrome, P=0.339 and 0.914 for corrective and palliative group, respectively).
2.5. Late aortic events
Of 3616 patients surviving over 6 months after their initial presentation of aortic dissection (78% of palliative group and 69% of corrective group; Fig. 4A)
, 96 underwent surgical intervention for recurrent events related to aortic dissection or aneurismal evolution during the follow-up period, and another 103 patients died of aortic causes (ICD-9: 441). Incidence of late aortic events, defined by both of the above events, was 2.48% per year, comparable between corrective and palliative group (P=0.708; Fig. 4A).
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Fig. 4. (A) Freedom from recurrence of aortic dissection (re-operation or death due to aortic causes) in cases surviving over 6 months. (B) Hazard rate of recurrence of aortic dissection.
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The hazard of late aortic events was stable from 6 months to 4 years, followed by a steep increase to the end of follow-up period (Fig. 4B). In multivariate analysis, young age was a significant risk factor of late aortic events for corrective group (relative risk of 0.95–0.98 per year, P=0.037), while male gender and Marfan syndrome were not (P=0.817 and 0.612, respectively). For palliative group, old age, male gender, and Marfan syndrome were all significant risk factors of late aortic events (relative risk of 1.01–1.02, 1.46–2.1, and 4.08–10.7, and P=0.037, 0.002, and <0.001, respectively; Table 3).
To validate the differential effect of age on late aortic events between both groups, the incidence of late aortic events from 6 months to 6 years was plotted by their age decades (Fig. 5)
. For corrective group, an inverse relationship between age and the incidence was clearly demonstrated, but for palliative group, the incidence was relatively constant except some elevation in the fifth decade.
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Fig. 5. Incidence of late aortic events, grouped by their initial age decades, between 6 months and 6 years for both groups. Case numbers in each group were indicated on the top of the bar.
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3. Discussion
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The present study, to our knowledge, comprises the largest patient cohort of aortic dissection with follow-up data. Trivial but important trend of late aortic events and their risk factors could be revealed by such large-scaled database. From the results of the present study, we found 31% in corrective group and 22% in palliative group died in the first 6 months after their initial presentation of aortic dissection, and annual attrition rate after that period were 2.3% for corrective group and 5.8% for palliative group. The incidence of late aortic events was 2.48% per year on average, with an increasing trend since the fourth year after their initial episode. Palliative treatment for Marfan patients and for male patients was with increased incidence of late aortic events, indicating broader operative indication and close follow-up for patients with these two risk factors.
Database of the present study was based on ICD-9 classification, by which aortic dissection involving ascending aorta (Stanford type A) cannot be differentiated from that involving descending aorta (type B). We try to use cardiopulmonary bypass procedure as grouping criteria. By this method, all the cases of type A dissection, as long as they received operation, and most of the cases of type B dissection needing a radical operation were grouped in corrective group. On the other hand, those with extremely poor condition (for example, prolonged shock, coma) that surgical procedures cannot rescue their lives, and those type B dissection receiving conservative medical treatment or only peripheral bypass surgery were grouped in palliative group. By this classification, the dissected aortic segments in palliative group were left untouched while the major part of severely injured aortic segments in corrective group were replaced, so it provides a chance to study the natural process of late aortic aneurysmal evolution of residual diseased aortic segments to reach a volume leading to complication and, then, re-operation or death.
3.1. Demographic data
Annual incidence of aortic dissection in our country by the present study (43 per 1 000 000 population) was comparable to that of IRAD study based on the population in the United States (5–30 per 1 000 000 population) [14]. The mean age, gender distribution, and immediate outcomes were also comparable between both studies.
3.2. Follow-up survival
The long-term survival of patients who had no apparent indication for surgery, namely, uncomplicated type B dissection, were unchanged over the past 20 years, ranging from 2.5 to 6% in annual attrition rate [15–17]. The pattern of survival curve in the present study is similar to previous reports [3,15,18]. By the strong selective effect of radical operation with cardio-pulmonary bypass, the early mortality rate was high in corrective group, but those who survived over 6 months had comparable long-term survival with their sex- and age-matched control group (Fig. 2). In contrast, without the selective effect of radical operation, the palliative group had a smooth and steadily decreasing surviving curve in the study period.
3.3. Causes of late mortality
Three leading causes of late mortality in the present study were, in accordance with previous reports [8,16], aortic causes, cardiac causes, and cerebral vascular incidences (Fig. 3). All these three causes were related to hypertension and accounted for a total of 61 and 48% of all late deaths for corrective and palliative group, respectively. This finding indicates the importance of persistent treatment on hypertension and its related diseases for this patient group.
An alternative interpretation of Fig. 3 is that all the five major causes of late mortality might be related to the sequels of aortic dissection. Hypertension and cardiomegaly was present in 80–95% of cases of aortic dissection [19], so the death of cardiac causes could be high in this patient group. Stroke, genito-urinary, and gastro-intestinal events might be related to the compromise of carotid, renal, and mesenteric arteries, respectively, which were all common complications after aortic dissection. Whatever the interpretation, it reminds us to closely follow-up the cases of aortic dissection not only on their dissected aorta, but also on multiple end-organs that are potentially involved in the disease process.
3.4. Late aortic events of aortic dissection
We use ‘late aortic events’ instead of ‘recurrence of aortic dissection’ by the reason that most of the late re-operation or complication were due to aneurysmal evolution of diseased aorta but not true re-dissection of aorta in the follow-up period [20]. The incidence of late aortic events in the present study was about 9% at 5 years, comparable to previous reports [8,21], and was much higher than the incidence of aortic dissection for the general population (43 per 1 000 000 population per year; Fig. 1). This finding suggests that sincere follow-up and rigorous medical treatment is mandatory for this patient group.
While the diseased aortic segment in palliative group was untouched, not all diseased aortic segment in corrective group was replaced. Many cases of type A dissection had both ascending and descending aortic dissection, but only ascending aorta were replaced in the operation. Therefore, they had diseased descending aortic segments as that in palliative group. Because some descending aortic dissection behaves more gravely than the others [6], there is a fixed percentage of the late events in this patient group. The present study showed that the incidence of late aortic events for the corrective group was no less than that for the palliative group, even the former group had experienced the crucial selection of the radical operation. By this, we suggest that equal attention must be paid on the prevention and early diagnosis of late aortic aneurysmal evolution for both corrective and palliative groups.
One interesting finding was the increasing incidence of recurrence of aortic dissection since the fourth year after their initial presentation (Fig. 4B). Similar finding was found in previous reports [16,17,22]. In one study based on 288 cases of operated aortic dissection, Rizzoli et al. [22] reported an 3.9% patient-year recurrence rate for type A dissection, and comparable recurrence rate for type B cases in their first 4 years of follow-up, followed by a steep increase in the incidence. The finding in the present study was in high accordance with that study. The lucid interval of 4 years can be explained by the theoretical time period needed for the dissected aorta to reach its critical size and clinical significance. Assuming that the diseased aortic segment at the initial episode is 5 cm on average [6], and the expansion rate of this diseased aorta is 0.4–0.8 cm per year [6], the period of 4 years is a reasonable estimate for this aortic segment to grow up to 6.6–8.2 cm and thus becomes symptomatic. This observation bears important clinical implication to warrant frequent image surveillance for patients with aortic dissection, especially since the fourth year after their initial presentation.
Male gender was a risk factor of late aortic events for palliative group (Table 3). Multiple explanations might contribute to this finding. First, the vigorous life style in male gender is associated with fluctuating blood pressure and high shear stress on the already diseased aorta, which could result in high incidence of its aneurysmal evolution. Secondly, poor compliance in medication and life style modification in male patients could result in poor control of blood pressure and high incidence of late events. The above explanation also explains the high incidence of mortality in the first 6 months for male patients in both corrective and palliative group (Table 2), in addition to the possibility of more severe pathology of aortic dissection at their initial presentation for male patients.
3.5. Marfan syndrome
Previous studies reported satisfactory surgical results for patients with Marfan syndrome mainly because of their young age, but suboptimal follow-up results due to high incidence of late aneurysmal evolution [20,23,24]. Our finding revealed that among cases in palliative group, Marfan patients carried 2–5 times the risk of death in the first 6 months and 4–10 times the risk of late aortic events in the follow-up as compared to non-Marfan patients (Table 3). This was comparable to previous studies and can be explained by the fact that the dissected aortic segments in Marfan patients were more liable to aneurysmal evolution due to impaired structural integrity [25]. It indicates that the generally accepted surgical guidelines for type B aortic dissection should be broadened for Marfan patients to prevent its late events.
In the present study, the late aortic events of Marfan patients in corrective group was comparable to that of non-Marfan patients (Table 3), which is different from major published results in this respect [20,23,24], in which a 30–50% re-operation rate were reported for Marfan patients after their initial surgical treatment of aortic dissection. The low incidence of late aortic events in the present study might be due to inadequate follow-up period (only 6 years), late operation years (1996–2001), incomplete inclusion of all Marfan cases for the statistical analysis, or modern anti-hypertensive medications. This difference and its possible causes must be taken into consideration when interpreting this data of the present study.
3.6. Age and late aortic events
Comparing Figs. 1 and 5, the incidence of aortic dissection was lower in young patients than in old ones, but the incidence of late aortic events for corrective group was higher in young patients. This discrepancy could be explained by that among young population with generally low incidence of aortic dissection, those who had this disease must have specific strong risk factors for it. Therefore, they might have extensive involvement of aortic dissection. Even after the emergency operation for the life-threatening dissecting aortic segment, those untouched diseased aortic segment in these patients still face high chance of late evolutional change due to both of their extensive involvement and strong underlying risk factors.
4. Limitations
Patients who died before reaching hospital had no chance for accurate diagnosis; hence the calculated incidence of aortic dissection might be lower than the real number.
Marfan syndrome was based on clinical diagnostic criteria and many patients of Marfan syndrome were not accurately diagnosed and coded, and those cases of aortic dissection in their 30–40 years might actually be Marfan patients. This might result in an underestimation of the true incidence of Marfan syndrome in our series.
Furthermore, only 6 years' follow-up data was available in the present study. It was because National Health Insurance in our country was established since 1996; therefore, only database after that period was available. This relatively short follow-up period might reveal only a part of the complete scenario of late aortic evolutional change after aortic dissection.
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5. Conclusions
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Large-scaled database such as one in the present study provides a broad vision on the outcome of aortic dissection. Aortic dissection appears as a relentless disease process in specific patient groups no matter what the initial management is. The incidence of late aortic events increased since the fourth year after their initial episode. Young age in corrective group, male gender and Marfan patients in palliative group had high incidence of late aortic events. Special consideration in the initial management and in late follow-up was warranted for these patients.
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Acknowledgments
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We acknowledge the generous provision of database for the present study from National Health Insurance Research Database of National Health Research Institutes, Taiwan, ROC, and Department of Statistics, Ministry of the Interior, ROC.
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Abstract
Introduction
