Intramural Hematoma and Penetrating Ulcers: Indications to Endovascular Treatment

Article Outline

• Abstract
• Introduction
• Intramural hematoma
• Penetrating aortic ulcer
• Recent insights into IMH and PAU
• Current indications for TEVAR in IMH and PAU
• Conclusion
• Conflict of Interest/Funding
• References
• Copyright

Abstract 

Intramural hematoma (IMH) of the aorta and penetrating aortic ulcer (PAU) are important variant forms of classic double-barrel aortic dissection in patients presenting with acute aortic syndrome. Recent insights provided by modern high-resolution imaging are currently challenging previous pathophysiologic concepts underlying IMH and PAU, suggesting a close relationship of both entities. Thoracic endovascular aortic repair (TEVAR) offers a less invasive approach to the treatment of affected patients with very encouraging early to midterm results. This review discusses current indication for TEVAR in IMH and PAU patients in the view of an improved understanding of these diseases.

Keywords: Penetrating aortic ulcer, Intramural hematoma, TEVAR, Stent-graft, Acute aortic syndrome

Back to Article Outline

Introduction 

Diseases of the thoracic aorta contribute significantly to the high overall mortality from cardiovascular disease.¹, ² In recent years, advances in modern high-resolution imaging have provided valuable insights into the pathophysiology of aortic diseases and have identified important subforms of classical double-barrel aortic dissection, resulting in a better understanding of acute aortic diseases.³, ⁴ Acute aortic syndrome (AAS), which contrasts nicely with acute coronary syndrome, describes patients who present with somewhat uniform sudden chest/back pain symptoms of sharp/tearing character (“aortic pain”), which are caused by various acute aortic diseases.⁴ The subsumption of such patients under the term “acute aortic syndrome” allows for a more uniform, standardized approach to diagnosis and management of acute aortic diseases.⁴

Acute aortic syndrome encompasses classic aortic dissection with true and false-lumen (class 1 dissection according to Svensson³) and less common variant forms or potential precursors of classic dissection such as intramural hematoma of the aortic wall (IMH, class 2 dissection), subtle dissection (class 3 dissection), which is found intraoperatively in Marfan patients, penetrating aortic ulcer (PAU, class 4 dissection), and iatrogenic or traumatic transsection of the aorta (class 5 dissection). In some patients, AAS may also be caused by symptomatic aortic aneurysm.², ⁵

The aim of this review is to summarise the currently available literature with respect to indication to endovascular treatment in patients presenting with IMH or PAU.

Back to Article Outline

Intramural hematoma 

Intramural hematoma accounts for approximately 6–10% of all acute aortic syndromes.⁶, ⁷ In Asian studies, the incidence of IMH among AAS patients was significantly higher, approximating 30–40% of patients.⁵, ⁸ First described by Krukenberg in 1920,⁹ IMH is commonly defined as bleeding into the outer layers of the aortic media, presumably caused by apoplectic rupture of aortic vasa vasorum, which are prone to rupture due to alterations from chronic arterial hypertension.¹, ⁴ By definition, IMH lacks a detectable intimal tear/disruption, and has therefore no communication with the true aortic lumen, but is confined within the aortic wall (“dissection without intimal tear”). On imaging IMH is identified by crescent-shaped or concentric thickening of the aortic wall, which in its early stage shows hyper-intensity on T2 imaging by MRI or hyper-density in non contrast-enhanced computed tomography (CT). Thus, IMH can even be detected on a native CT scan. Luminal displacement of intimal calcification may be helpful in differentiating IMH from mural thrombus. In addition, transesophageal echocardiography provides important information for diagnosing IMH.⁶ Intramural hematoma may affect the entire thoracic aorta and usually – similar to classic dissection – involves a longer segment of the aorta.

Symptoms of IMH may be very similar to those of classic dissection, and patients can not be reliably distinguished by clinical presentation alone.⁴ However, the risk of malperfusion is lower with IMH and thus symptoms of organ ischemia may be absent in IMH patients.

So far, the natural history of IMH is not fully understood. Published data are somewhat conflicting with some reporting a rather favorable outcome of IMH as compared to classic dissection, whereas others have reported similar mortality and complication rates to double-barrel dissection.⁵ Complications of IMH are quite common and include progression towards overt false-lumen dissection in 28–47% of cases, early aneurysm formation or (contained) rupture in 20-45% of patients.⁷ Patients may, however, show spontaneous reabsorption of IMH under medical treatment, although regression is less common. Predictors of progression include recurrent or persisting pain, and presence of penetrating aortic ulcer, while younger age, aortic diameter <4.0–4.5cm, and hematoma thickness <1.0cm portend a better prognosis.⁴, ⁵

Previous studies have shown that the location of the IMH is of paramount importance for patient's prognosis. In analogy to the Stanford classification of classic aortic dissection, involvement of the ascending aorta (type A-IMH) demands urgent surgical repair in most of the patients due to the risk of rupture or progression to frank dissection. It should, however, be noted that in particular groups from Japan and Korea have documented a more benign course of type A-IMH with non-operative management, recommending primarily strict blood pressure control, prolonged bed rest (4 weeks), and close imaging surveillance.⁷, ⁸ It has been speculated that the relatively low mortality rate in Asian IMH patients may be explained by a genetic factor or the fact that more limited IMHs were included in these series.⁷ Intramural hematoma confined to the aortic arch or the descending thoracic aorta (type B-IMH) may primarily be safely treated non-surgically with close imaging follow-up.

Back to Article Outline

Penetrating aortic ulcer 

Penetrating aortic ulcer of the aorta has first been described by Shennan in 1934,¹⁰ but has only recently been acknowledged as a distinct pathologic variant of classic false-lumen aortic dissection.¹¹ Previous investigators have estimated that 2.3–7.6% of acute aortic syndromes are caused by PAU.¹² Penetrating atherosclerotic ulcer is defined by an ulceration of an aortic atherosclerotic plaque penetrating through the internal elastic lamina into the aortic media.¹¹

Penetrating aortic ulcer occurs most often in patients with extensive atherosclerotic disease.¹¹ Therefore, usually patients in their 7th life decade and older are affected by PAU. Similar to IMH, patients may not be distinguished from classic dissection by clinical presentation alone, since symptoms may be very similar. Penetrating aortic ulcer has a characteristic appearance on angiography, reminiscent of duodenal ulcer. Nowadays, angiography is only rarely performed to diagnose PAU, whereas non-invasive imaging modalities, which in addition provide important information on the tissue surrounding the aorta, are used more frequently. On imaging, PAU typically appears as one or more focal, contrast-material filled, craterlike outpouchings of the lumen, with a thickened aortic wall and inward displacement of calcified intima by concomitant intramural haematoma.¹³ Penetrating ulcers have been described along the whole length of the aorta but most commonly involve the mid and distal descending thoracic aorta. There is a strong association of PAU with concomitant abdominal aortic aneurysms. Penetrating ulcers of the ascending aorta (type A PAU) are rare, but dreadful requiring urgent surgical repair in most patients.⁴, ¹³

Complications of PAU include development of (localized) intramural hematoma due to arrosion of aortic vasa vasorum by the ulcer, (pseudo)aneurysm formation, progression to overt aortic dissection, or rupture in up to 40% of patients.⁴, ¹⁴, ¹⁵, ¹⁶

Again similar to IMH, the natural history of PAU is not fully understood yet. There are conflicting data in the literature with respect to disease behaviour.¹⁴, ¹⁵, ¹⁶ While some authors reported PAU to be malignant,¹¹, ¹⁴, ¹⁵, ¹⁶ others reported a lower incidence of life-threatening complications.¹⁷, ¹⁸ It appears that symptomatic patients presenting with AAS caused by PAU have a worse prognosis than those who are asymptomatic and PAU is found incidentally on axial imaging.

Back to Article Outline

Recent insights into IMH and PAU 

The rigorous classic definition of IMH as being a “dissection without a tear” has long been doubted by several investigators postulating the presence of an intimal tear/disruption that may be not detectable with previously available imaging modalities (Fig. 1). Moreover, it appears that IMH and PAU may not only be distinct entities, but there may be a considerable overlap between both. This controversy highlights that – at present – both pathophysiology and natural history of IMH and PAU are not fully understood.

• 
  • View Large Image
  • Download to PowerPoint

• Figure 1 

  A+B. IMH (asterisk) with plaque ulceration/intimal disruption (arrow) in the mid part of the descending thoracic aorta in a patient with acute aortic syndrome. C+D. Complete reabsorption of the IMH 1 year after TEVAR.

Recent observations from the Vienna group have challenged the classical hypothesis of IMH being a dissection without a tear.¹⁹ Michael Grimm has provided important novel insights into mechanisms underlying IMH of the entire aorta.¹⁹ Grimm et al. detected small atherosclerotic plaque ruptures at the free lateral wall or at the concavity of the aortic arch as the cause of IMH in 8 previously unrecognised patients with IMH involving the entire aorta (including ascending aorta). Detection of these discrete lesions was accomplished by the use of modern high-resolution ECG-gated CT angiography, applying mulitplanar reconstructions in parasagital orientation. They found that if the ulcer is at the convexity of the distal arch, supra-aortic branches prevent retrograde extension toward the ascending aorta.¹⁹ Conversely, if the ulceration site is found at the free lateral wall or at the concavity of the arch, IMH may extend retrogradly into the ascending aorta, as well as antegradly into the descending aorta. Consequently following their hypothesis, Grimm et al.¹⁹ used the ulceration site as the landing zone for thoracic aortic endovascular repair (TEVAR). Most interestingly, they observed resorption of IMH especially within the ascending aorta in all patients, although the stent-graft was placed in the distal arch (Fig. 2).

• 
  • View Large Image
  • Download to PowerPoint

• Figure 2 

  A. Contrast-enhanced CT of a patient presenting with acute aortic syndrome showing type A-IMH (asterisk) with evolving dissection in the descending aorta. B. Multiplanar reconstruction of the CT in parasagittal orientation delineates small intimal disruption/plaque rupture as the initial site of the IMH (arrow, asterisk-IMH). C. Transesophageal echocardiography showing active bleeding from the aortic lumen into the hematoma (arrow). D. Result after TEVAR with stent-implantation into the distal arch. Note complete reabsorption of the type A-IMH, as well as near-total resolution of descending thoracic aortic IMH. E. TEVAR result shown by intraoperative TEE, showing elimination of flow into the IMH.

Grimm et al.¹⁹ suggested that rupture of a small atherosclerotic plaque may be the underlying mechanism of IMH formation in their patients, which deserves further discussion. As highlighted above, PAU may indeed lead to IMH due to arrosion of vasa vasorum, which is observed in many PAU cases; however, in its classical sense this type of IMH is thought to be segmental and may thus not affect the entire aorta. One could therefore also hypothesize that the ulceration site as detected by Grimm et al.¹⁹ is caused by the wall hematoma resulting in high pressure within the aortic wall, leading to secondary intimal disruption, rather than a primary rupture of an atherosclerotic plaque from the aortic lumen into the wall, subsequently leading to antegrade or retrograde extension of the hematoma by the high-pressure blood stream. This may be further corroborated by the clinical observation that advanced calcific atherosclerosis in IMH – similar to patients with classic dissection – is a somewhat rare finding. Further improvements in imaging techniques will hopefully help to better understand the relationship between IMH and PAU and provide a better understanding of the underlying pathophysiologic mechanisms.

Ganaha et al.²⁰ have also addressed this overlap of IMH and PAU, highlighting substantial differences in the clinical features and the patients' prognoses in patients with an IMH caused by PAU and those with an IMH not associated with a PAU. They retrospectively analysed 65 symptomatic patients with IMH. Patients in whom IMH was found to be associated with PAU had a significantly worse prognosis than those with IMH unaccompanied by PAU.²⁰ The rate of progression was 48% in patients with IMH and PAU and only 8% in patients with IMH alone. Interestingly, Ganaha et al.²⁰ identified persistent or recurrent pain despite aggressive treatment and an interval increase of pleural effusion as clinical predictors of disease progression. As for the implications of initial PAU size, maximum diameter (>20mm at initial measurement) and depth (>10mm) both correlated significantly with disease progression.²⁰

Back to Article Outline

Current indications for TEVAR in IMH and PAU 

Current indications for TEVAR in type B-IMH in general cover patients with disease progression or evolving complications such as overt dissection and (contained) rupture or patients unresponsive to antihypertensive treatment (i.e. persistent chest pain).² The observations of Grimm et al.¹⁹ have provided the pathophysiologic basis for implantation of covered stent-grafts into the aorta affected by IMH. In general, long stent-grafts with a length of 20–25cm should be preferred in order to cover additional intimal disruption sites. High-resolution imaging using multi-detector CT angiography with MPR reconstructions is paramount in all IMH patients in order to detect even discrete lesions, which feed the hematoma. As these lesions are frequently located in the distal arch, care must be taken to place the stent-graft proximal within the arch so that it covers the ulceration/disruption site. This may require intentional overstenting of the ostium of the left subclavian artery, which mandates prior evaluation of cerebral and vertebral arteries before the procedure. It is an interesting clinical observation, which is not supported by currently published literature, that most IMH patients with refractory pain will be pain-free after a TEVAR procedure. In the view of the Grimm findings, it is further tempting to speculate that TEVAR may also be applied for patients with IMH affecting the ascending aorta (Fig. 2) in lieu of surgical repair. However, this requires further multi-center studies due to the small number of patients in the individual institutions and can not be recommended routinely at this point in time.

For PAU, so far no generally accepted therapeutic regimen has been established.¹³, ²¹ Initially asymptomatic patients with incidental PAU finding are followed with further imaging. Initially symptomatic but stable patients with involvement of the descending aorta (type B-PAU) may be managed conservatively with tight blood pressure control, if pain at initial presentation resolves with medical therapy and there is no radiological evidence of deterioration during short-term follow-up. Close clinical and imaging follow-up is, however, mandatory. A more aggressive therapeutic approach is advocated in symptomatic high-risk patients. In this regard, the presence of pain at admission and the diameter of the involved aortic segment are important predictors of aortic rupture; but rupture may still occur in normal-sized aortas. Unrelenting or recurrent pain and/or interval increase in pleural effusion have also been identified as predictors of disease progression.²⁰ Recent data suggest that evaluation of inflammation accompanying acute aortic syndrome by PET-CT may help to identify patients at risk for disease progression (Fig. 3).²²

• 
  • View Large Image
  • Download to PowerPoint

• Figure 3 

  A. Penetrating aortic ulcer (arrow) in an acute aortic syndrome patient. B. Fused PET-CT image showing increased glucose metabolism within the PAU (arrow). C. Progression towards pseudoaneurysm formation (arrow) under medical treatment. D. Result after TEVAR with complete resolution of the ulcer.

Given the segmental nature, PAU has been considered an “ideal” target which can be completely excluded with a single piece stent-graft.¹³ However, patients are usually elderly with advanced atherosclerosis which may entail difficult vascular access as well arch disease increasing the risk of embolic stroke during the procedure.⁵, ¹³ So far available results of TEVAR in type B-PAU are very encouraging (Table 1), supporting its use in patients with complications of PAU such as pseudoaneurysm formation or (contained) rupture.

Table 1. Overview of other published studies on TEVAR in PAU patients..

Back to Article Outline

Conclusion 

Intramural hematoma and penetrating ulcers are important variant forms of classic aortic dissection. There is currently evolving evidence that both entities may not be distinct diseases, but there may be considerable overlap in the pathophysiology of both. Recent studies highlighted that an ulceration or intimal disruption site is often detected in IMH patients, when modern high-resolution imaging techniques with profound post-processing are used. This may provide an adequate target for a TEVAR procedure which is currently indicated in patients with progression of IMH towards overt dissection or (contained) rupture. Similarly, TEVAR is indicated in symptomatic patients with PAU complicated by pseudoaneurysm formation or rupture. Future studies will hopefully help to gain a better understanding of these important causes of acute aortic syndrome.

Back to Article Outline

Conflict of Interest/Funding 

None.

Back to Article Outline

References 

1. Erbel R. Diseases of the thoracic aorta. Heart. 2001;86:227–234
   • View In Article
2. Svensson LG, Kouchoukos NT, Miller DC, Bavaria JE, Coselli JS, Curi MA, et al. Expert consensus document on the treatment of descending thoracic aortic disease using endovascular stent-grafts. Ann Thorac Surg. 2008;85:S1–S41
   • View In Article
   • CrossRef
3. Svensson LG, Labib SB, Eisenhauer AC, Butterly JR. Intimal tear without hematoma: an important variant of aortic dissection that can elude current imaging techniques. Circulation. 1999;99:1331–1336
   • View In Article
   • MEDLINE
4. Erbel R, Alfonso F, Boileau C, Dirsch O, Eber B, Haverich A, et al. Diagnosis and management of aortic dissection. Eur Heart J. 2001;22:1642–1681
   • View In Article
   • MEDLINE
   • CrossRef
5. Sundt TM. Intramural hematoma and penetrating aortic ulcer. Curr Opin Cardiol. 2007;22:504–509
   • View In Article
   • CrossRef
6. Mohr-Kahaly S, Erbel R, Kearney P, Puth M, Meyer J. Aortic intramural hemorrhage visualized by transesophageal echocardiography: findings and prognostic implications. J Am Coll Cardiol. 1994;23:658–664
   • View In Article
   • Abstract
   • Full-Text PDF (2667 KB)
   • CrossRef
7. Evangelista A, Mukherjee D, Mehta RH, O'Gara PT, Fattori R, Cooper JV, et al. Acute intramural hematoma of the aorta: a mystery in evolution. Circulation. 2005;111:1063–1070
   • View In Article
   • CrossRef
8. Song JK, Kim HS, Kang DH, Lim TH, Song MG, Park SW, et al. Different clinical features of aortic intramural hematoma versus dissection involving the ascending aorta. J Am Coll Cardiol. 2001;37:1604–1610
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (419 KB)
   • CrossRef
9. Krukenberg E. [Contribution to the question of dissecting aneurysm], Beitr Pathol Anat Allg Pathol. 1920;67:329–351
   • View In Article
10. Shennan T. Dissecting aneurysms. Medical research council, special report series No 193. London: HMSO; 1934;
    • View In Article
11. Stanson AW, Kazmier FJ, Hollier LH, Edwards WD, Pairolero PC, Sheedy PF, et al. Penetrating atherosclerotic ulcers of the thoracic aorta: natural history and clinicopathologic correlations. Ann Vasc Surg. 1986;1:15–23
    • View In Article
    • Abstract
    • Full-Text PDF (944 KB)
    • CrossRef
12. Vilacosta I, San Roman JA, Aragoncillo P, Ferreiros J, Mendez R, Graupner C, et al. Penetrating atherosclerotic aortic ulcer: documentation by transesophageal echocardiography. J Am Coll Cardiol. 1998;32:83–89
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (565 KB)
    • CrossRef
13. Eggebrecht H, Baumgart D, Schmermund A, Herold U, Hunold P, Jakob H, et al. Penetrating atherosclerotic ulcer of the aorta: treatment by endovascular stent-graft placement. Curr Opin Cardiol. 2003;18:431–435
    • View In Article
    • MEDLINE
    • CrossRef
14. Coady MA, Rizzo JA, Hammond GL, Pierce JG, Kopf GS, Elefteriades JA. Penetrating ulcer of the thoracic aorta: what is it? How do we recognize it? How do we manage it?. J Vasc Surg. 1998;27:1006–1015
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (2930 KB)
    • CrossRef
15. Coady MA, Rizzo JA, Elefteriades JA. Pathologic variants of thoracic aortic dissections. Penetrating atherosclerotic ulcers and intramural hematomas. Cardiol Clin. 1999;17:637–657
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (1486 KB)
    • CrossRef
16. Tittle SL, Lynch RJ, Cole PE, Singh HS, Rizzo JA, Kopf GS, et al. Midterm follow-up of penetrating ulcer and intramural hematoma of the aorta. J Thorac Cardiovasc Surg. 2002;123:1051–1059
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (1252 KB)
    • CrossRef
17. Harris JA, Bis KG, Glover JL, Bendick PJ, Shetty A, Brown OW. Penetrating atherosclerotic ulcers of the aorta. J Vasc Surg. 1994;19:90–98
    • View In Article
    • Abstract
    • Full Text
    • CrossRef
18. Quint LE, Williams DM, Francis IR, Monaghan HM, Sonnad SS, Patel S, et al. Ulcer like lesions of the aorta: imaging features and natural history. Radiology. 2001;218:719–723
    • View In Article
    • MEDLINE
19. Grimm M, Loewe C, Gottardi R, Funovics M, Zimpfer D, Rodler S, et al. Novel insights into the mechanisms and treatment of intramural hematoma affecting the entire thoracic aorta. Ann Thorac Surg. 2008;86:453–456
    • View In Article
    • CrossRef
20. Ganaha F, Miller DC, Sugimoto K, Do YS, Minamiguchi H, Saito H, et al. Prognosis of aortic intramural hematoma with and without penetrating atherosclerotic ulcer: a clinical and radiological analysis. Circulation. 2002;106:342–348
    • View In Article
    • CrossRef
21. Eggebrecht H, Herold U, Schmermund A, Lind AY, Kuhnt O, Martini S, et al. Endovascular stent-graft treatment of penetrating aortic ulcer: results over a median follow-up of 27 months. Am Heart J. 2006;151:530–536
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (310 KB)
    • CrossRef
22. Kuehl H, Eggebrecht H, Boes T, Antoch G, Rosenbaum S, Ladd S, et al. Detection of inflammation in patients with acute aortic syndrome: comparison of FDG-PET/CT imaging and serological markers of inflammation. Heart. 2008;94:1472–1477
    • View In Article