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Eur J Cardiothorac Surg 2008;33:1002-1006. doi:10.1016/j.ejcts.2008.02.016
Copyright © 2008, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
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Optimal initial treatment and clinical outcome of type A aortic intramural hematoma: a clinical review

Chung-Ben Kana, Rei-Yeuh Changb, Jen-Ping Changc,*

a Division of Cardiovascular Surgery, Department of Surgery, Chia-Yi Christian Hospital, Taiwan, ROC
b Division of Cardiovascular Medicine, Department of Internal Medicine, Chia-Yi Christian Hospital, Taiwan, ROC
c Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University, College of Medicine, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien 833, Taiwan, ROC

Received 2 December 2007; received in revised form 10 February 2008; accepted 14 February 2008.

* Corresponding author. Tel.: +886 7 731 7123; fax: +886 7 731 8762. (Email: c9112772{at}adm.cgmh.org.tw).


   Abstract
Top
 Abstract
1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Intramural hematoma (IMH) of the aorta is a well-known variant of aortic dissection; however, the optimal initial treatment strategy for type A IMH remains controversial. An English language search of Medline for manuscripts on the treatments and outcomes of IMH with the keywords ‘intramural hematoma’, ‘ascending aorta or type A’, ‘aortic disease’ with cross-references was performed for articles dating from January 1986 to September 2006. Primary outcomes of interest were initial treatment strategies as well as the early and overall mortality rates. Earlier publications studying overlapping patient groups from the same institutions were excluded. Case reports and small series of less than 10 patients were not enrolled. Data from 328 reported cases in 12 studies were extracted. Initial surgery and medical treatment were performed for 168 (51.2%) and 160 (48.8%) patients, respectively. Nine out of 12 studies (75%) came from Asia. The early mortality rate was 10.1% (17/168) and 14.4% (23/160) in patients who received initial surgery and medical treatment, respectively (p = 0.37). The optimal initial treatment strategy for type A IMH may still be individualized. Initial medical treatment and timed surgical therapy seems to be associated with higher early mortality rates in patients with type A IMH, even in a primarily Asian cohort. The impact of either initial treatment strategy on long-term survival must be evaluated in further study.

Abbreviations: AD = aortic dissection • IMH = intramural hematoma • PAU = penetrating atherosclerotic ulcer

Key Words: Aortic dissection (includes ulcers, hematomas) • Aortic operation


   1. Introduction
Top
 Abstract
 1. Introduction
2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Aortic intramural hematoma (IMH) is an acute, potentially lethal disorder that is similar to, but pathologically distinct from, acute aortic dissection. In patients with uncomplicated IMH involving only the descending aorta, or aortic arch, the consensus is that medical treatment is recommended [1]. The optimal initial treatment strategy for type A IMH remains controversial. Because of the lesser prevalence of the disease entity, publication updates were limited to a small number of patients in either hospital. To our knowledge, there has been no meta-analysis or systematic review to evaluate treatment strategies for type A IMH patients. Therefore, we conducted a clinical review of recent publications to analyze the optimal initial treatment strategy with relation to clinical outcome.


   2. Materials and methods
Top
 Abstract
 1. Introduction
 2. Materials and methods
3. Results
 4. Discussion
 5. Conclusions
 References
 
2.1 Search strategy
An English language search of Medline for manuscripts on outcomes of IMH with the keywords ‘intramural hematoma or hemorrhage’, ‘ascending aorta or type A’, ‘aortic disease’ with cross-references was performed. Earlier publications studying overlapping patient groups from the same institution were excluded. Case reports and small series of less than 10 patients were not enrolled. Studies that did not declare the clinical outcome were also excluded. Primary outcomes of interest were the initial treatment strategy and the early (<30-day or in-hospital) and overall mortality rates. Survival data were collected at 1-, 2-, 3-, 5- and 10-year intervals if available. Data from 328 reported cases in 12 studies were extracted [1–12].

Three reviewers (two surgeons and one physician) collected the data using a standard data abstraction form. All disagreements were resolved by discussion and consensus. Clinical information including patient age, sex, comorbidities and management strategies was collected. The outcomes and the long-term survival rate after medical and surgical treatment were also collected.

2.2 Statistical methods
Values were presented as mean ± SD or frequencies. The data were then subjected to statistical analysis using an independent-sample t-test. The level of significance was defined as p < 0.05. Statistical analysis was performed using SPSS software (SPSS for Windows, release 10.0) and Review Manager 4.2.9.


   3. Results
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
4. Discussion
 5. Conclusions
 References
 
3.1 Studies
A total of 328 cases in 12 studies of type A IMH were analyzed. Nine out of 12 studies (75%) came from Asia (Tables 1 and 2 ). During the analysis, considerable heterogeneity regarding the individual studies was noted. Patients were diagnosed within 48 h in all but six series (<2 weeks) [1,7,8,10–12]. Cases with penetrating atherosclerotic ulcer (PAU) were excluded in all but five studies [1,3–5,10]. Cases featuring intimal disruption were excluded in all but two series [3,10]. Patients were divided into two groups according to the initial treatment strategy utilized (Table 2, Fig. 1 ).


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  		Table 1 Patient characteristics and comorbidities available in 12 reports
 

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  		Table 2 Early mortality in relation to initial treatment
 

Figure 1
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  		Fig. 1. Forest plot of early mortality rates in patients with type A IMH comparing initial surgical treatment with initial medical treatment. (Two studies were excluded due to exclusively surgical or medical treatment.)

 
3.2 Samples size
Samples sizes for selected studies averaged 27.3 ± 17.4 patients (ranged from 10 to 69). Initial surgery and medical treatment were performed in 168 (51.2%) and 160 (48.8%) patients, respectively. Twenty-nine patients (18.1%) in the medical group underwent late operation (>48 h) due to progression of the disease (Table 2).

3.3 Patients survival
The early mortality rate was 10.1% (17 in 168 patients) for patients treated surgically and 14.4% (23 in 160 patients) for patients treated medically with a p value of 0.36 (Table 2). Fig. 1 presents a forest plot comparing early mortality rates in patients with type A IMH who received initial surgical treatment with those who received initial medical treatment. Long-term survivals are presented in Table 3 .


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  		Table 3 Averaged weighted reported overall survival of type A IMH
 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
5. Conclusions
 References
 
Aortic IMH was first described by Krukenberg in 1920 as ‘aortic dissection (AD) without intimal tear’ [13]. Between 1983 and 1992, Robbins et al. [14] managed 13 patients with IMH; the diagnosis of IMH were established by exclusion. According to the International Registry of Aortic Dissection [1], IMH was defined as an aortic wall hematoma without a demonstrable intimal flap on imaging study and no radiologically apparent intimal tear. Although hemorrhage into the aortic media occurs, an intimal tear with resultant false lumen is not present in IMH. Instead, hemorrhage occurs within the aortic wall due to either rupture of the vasa vasorum or less commonly, an atherosclerotic, penetrating aortic ulcer. Serial radiological follow-up is of prominent importance. Spontaneous absorption is a frequent phenomenon encountered in type A IMH and has been reported to have a good long-term prognosis [6]; however, progression of disease may be happening even many years after its first attack.

Most of the studies suggest that IMH may have clinical presentation and symptoms similar to those of classic AD, so called acute aortic syndrome. However, patients with type A IMH may have lower incidence of severe complications (pericardial tamponade or aortic regurgitation) compared to those with type A AD. As demonstrated in Table 1, data of pericardial effusion were available in 11 studies (318 patients in total) and the prevalence rate is 47 ± 18%. Data of aortic regurgitation were available in four studies (100 patients in total) and the prevalence rate is 21 ± 16%.

IMH accounts for 5–20% of patients with acute aortic syndromes [15,16]. Autopsy studies and clinical series have similarly shown that 10–41% of patients diagnosed with AD in fact had IMH [17–19]. Asian patients seemed to have a higher prevalence of IMH [8]. IMH patient cohorts tended to be older [10], and less likely to have limb ischemia, pulse deficits or aortic valve insufficiency [1,5]. Patients with IMH also had a higher prevalence of hypertension than those with AD [4]. The disease showed a marked predilection for the descending thoracic aorta [10].

Diagnosis of type A IMH was now established with transesophageal echocardiography, contrast-enhanced computed tomography or magnetic resonance imaging. IMH was defined as maximal crescent or circular thickening of the aortic wall of more than 7 mm. In addition, absence of dissection flap, intimal tear, or penetrating atherosclerotic ulcer was also a prerequisite for diagnosis of IMH [6].

IMH has a variable and dynamic clinical course. While 25–100% of medically treated IMH patients experienced partial or complete resolution [6–8,10,16,20], IMH also progressed to classic AD or aneurysm formation in up to 40% of cases [7,16,17,20,21]. Predictors of progression or regression were evaluated; the maximal aortic diameter <45 mm [20] or <50 mm [21] was noted to be a sensitive and specific favorable factor. Age was another noted factor. While younger patients were noted to have high regression rate in one study [20], older patients had better prognoses in most reports. The disappearance of an IMH during follow-up may suggest a good long-term prognosis [20]. Interestingly, transition from classic AD with a false lumen to aortic IMH has also been reported [22].

Proximal (type A) IMH occurred in about 40% of all IMH patients on average (ranging from 20% to 60%) [17]. Most studies have supported the view that the complication and mortality rates in proximal aortic IMH are higher than those of distal IMH [15,17]. Based on the pioneering reports of the 1990s, due to the high morbidity and mortality rates associated with medical treatment, it was concluded that IMH was associated with a clinical profile and prognosis similar to AD, and that the optimal management of patients with type A IMH was emergent surgical repair [5,12,15–17]. The early mortality rate of patients with type A AD ranges from 12% to 36% [23–25], in contrast, the operative mortality rate of patients with type A IMH was reported to be 6–17% [10].

Many reports indicate that the involvement of the ascending aorta is a key factor of predicting the early and late progression of IMH [5]. Early progression seems unrelated to age, sex, hypertension, Marfan syndrome, bicuspid aortic valve and either local extent or diameters at the site of IMH [5]. A maximal aortic diameter of <50 mm seems a favorable prognostic indicator in proximal IMH [21], patients with an aortic diameter >50 mm demonstrated a tendency for progression to dissection or aortic enlargement [21,26]. This cut-off value of 50 mm has a positive predictive value of 83% and a negative predictive valve of 100%, but age-related normal values should never be overlooked. However, IMH with normal to moderately enlarged aortic diameter does not preclude progression [5]. A hematoma thickness of 11 mm was also reported as a predictor of the adverse outcomes in medically treated patients with sensitivity 89% and specificity 69%, as well as positive and negative predictive value of 62% and 92%, respectively [27]. In addition, the cut-off value for the thickness of the aortic wall 2 weeks after admission was proposed to be 12 mm, with a positive and negative predictive value of 80% and 100%, respectively [4].

Several reports have documented the pathologic characteristics of type A IMH. The site of dissection in IMH is reported to be nearer the adventitial side of the media than that in AD, indicating that the wall of the false lumen is thinner in IMH than in AD [3,28]. The progression of dissection closer to the adventitia most likely discourages re-entry and may be related to the high incidence of rupture in IMH. These pathologic features may also explain the high incidence of fluid extravasation in acute IMH patients [29]. Pericardial effusion is a dominant symptom in type A IMH and has been reported to occur in 75–100% of IMH patients; it was noted in 47% of patients in this study [30,31]. Pericardiocentesis was reported to have good results on medically treated patients with cardiac tamponade [6,21,27]. However, others believe that cardiac tamponade associated with acute aortic catastrophes requires urgent surgical therapy [32].

Emergent operation is indicated for patients with aortic rupture or aortic valve regurgitation. Therefore, for patients treated medically, a series of image follow-ups is strongly recommended; the IMH might progress to overt dissection or frank rupture, and the aorta might also continue to grow, at a reported rate of 0.40–0.75 cm/year [4,33].

In general, the operative strategies of type A IMH were similar to or simpler than those for classical AD. Supracoronary ascending aortic replacement is the most common procedure performed, followed by hemiarch replacement. Composite valve grafting was seldom used. Resuspension of the regurgitant aortic valve is more preferred to replacement [5]. In the earlier series, femoral cannulation with hypothermic circulatory arrest was popular. Selective cerebral perfusion is used while aortic arch repair is indicated [10]. Open anastomosis and right axillary artery cannulation are not emphasized in any study reviewed, although these techniques are popular in the current era.

Regarding the early mortality rate of type A IMH, global experience supports a trend towards better outcomes after initial surgical treatment of proximal IMH [5]. In most instances, surgery of type A IMH consists of a simple straightforward procedure (simple replacement of the ascending aorta) whereas acute AD often requires sophisticated and difficult techniques. This may speak in favor of the surgical treatment and certainly explain the mostly good results obtained after surgery. In contrast, some recent Asian series have reported low mortality rates for type A IMH after initial medical treatment, indicating a possible ‘Asian factor’ [6,29].

To our knowledge, this study is the first clinical review concerning initial treatment strategies and early outcomes for type A IMH cohorts. Of the 328 patents enrolled, the early mortality rate for those who received initial medical treatment (14.4%) is 42.6% higher than those who received initial surgical treatment (10.1%). Although statistically not significant (p = 0.36), this result is consistent with and supports the concept that surgical treatment of type A IMH should not be delayed [5,12,15–17]. Moreover, the operative results for AD and IMH have been markedly improving [10,23–25].

4.1 Limitations of the study
Our study has some limitations. First of all, the primary drawback of this report is the absent of long-term survival for patients in either group. Given the high incidence of aortic rupture, medically treated type A IMH patients inherently face fatal risk. Many patients eventually require a late operation (18.1%) due to the progression of the disease.

Second, the definition of IMH is still under debate. Because the subtypes of this particular disease entity, which include patients with or without PAU and vasa vasorum rupture, have such similar clinical and radiological features with different clinical courses, the lack of universal definition of IMH makes this study heterogeneous and confusing.

Third, the patients in both the medical treatment and the surgical repair group were neither randomized nor demographically comparable. Therefore, it is possible that the better survival of patients was the result of referral bias based on patient condition [15].

Fourth, the sample size (n = 328) in this clinical review was small and limited. A future study with more patients enrolled may be more convictive of the optimal initial treatment strategy.


   5. Conclusions
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
References
 
The optimal initial treatment strategy for type A IMH may still be individualized. However, considering the relative higher mortality in patients with initial medical treatment and the recent improvement in surgical results [5,10,23–25]; we believe that evidence suggests that symptomatic patients and those with rapid progression or overt dissection during follow-up should receive emergent surgery. Furthermore, based on previously reported data, patients with ascending aortic diameter of more than 50 mm [21] or subadventitial hematoma thickness of more than 12 mm [4,27] should be considered as the candidates for early surgery.


   Acknowledgments
 
The authors wish to thank Candice Wei for her editorial assistance.


   References
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 

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