Penetrating Atheromatous Ulcer as a Precursor of Aortic Dissection: A Case Report

Background: Acute aortic syndromes include a range of life-threatening conditions with the most familiar entity being aortic dissection. However, variants of aortic dissection also include intimal tear without hematoma, aortic intramural hematoma, and lastly penetrating aortic ulcer (PAU), which will be the focus of this case report. Most PAUs are located in the descending thoracic aorta (85-95%), but they can also occur in the ascending aorta or arch as in the current case. Case Presentation: We report a case of a 77 year old male who presented with chief complaint of intermittent right-handed weakness associated with no numbness or mental status changes. Patient was admitted for stroke workup with unrevealing �ndings on CT (computed tomography) for acute abnormalities or any hemodynamically signi�cant stenosis on carotid ultrasound. CT angiogram of head/neck revealed a penetrating aortic ulcer of the lateral aspect of the mid to distal ascending aorta. Patient was then transferred for further evaluation to a center of higher level care for further management. Conclusions: Patient was evaluated for surgical repair of penetrating ascending aortic ulcer. Patient underwent serial imaging throughout hospital course which showed grossly similar �ndings to prior examination and thus no surgical intervention was needed at that time. Patient was recommended to have follow up CT scan in one month to monitor progression of aortic ulcer. Penetrating aortic ulcers are rarely located in the ascending aorta and are considered precursors of life-threatening aortic dissections.


Background
Acute aortic syndromes include a range of life-threatening conditions with the most familiar entity being aortic dissection.However, variants of aortic dissection also include intimal tear without hematoma, aortic intramural hematoma, and lastly penetrating aortic ulcer, which will be the focus of this case report.
Penetrating aortic ulcers (PAU) occur when the ulceration of an aortic atherosclerotic lesion penetrates the internal elastic lamina into the media in varying amounts, over which there may or not be an overlying thrombus.PAUs may be associated with hematoma within the media and may progress to perforation or aortic dissection, and are known to be the initiating lesion in < 5% of all aortic dissections.Most PAUs are located in the descending thoracic aorta (85-95%), but they can also occur in the ascending aorta or arch as in the current case.

Case Presentation
Acute aortic syndromes include a range of life-threatening conditions with the most well-known being aortic dissection.These syndromes most commonly cause a disruption in the layers of the aortic wall, most often initiated by an intimal injury of sorts.The major classi cations of aortic dissection begin with intimal tears without a hematoma, penetrating aortic ulcers, aortic intramural hematomas, and periaortic hematomas which all become equally as important when considering severity of illness.Penetrating aortic ulcers occur when the ulceration of an aortic atherosclerotic lesion penetrates the internal elastic lamina into the media in varying degrees, over which there may or may not be an overlying thrombus 1 .
PAUs may be associated with a hematoma within the media and may progress to perforation or aortic dissection, and are known to be the initiating lesion in < 5% of all aortic dissections ever since they were rst described 2 .Most penetrating aortic ulcers are located in the descending thoracic aorta (85-95%) 3 , and are rarely located in the ascending aorta or arch.
The general presentation of PAU is similar to that of the aforementioned aortic dissection etiologies, however the radiographic evidence is somewhat unique.Today, PAU is best diagnosed by contrastenhanced CT scanning demonstrating an outpouching ulcer crater, intimal calci cation, and localized intramural hemorrhage in conjunction with severe atherosclerotic disease.PAU tends to have a predilection in older gentlemen > 70 years of age with signi cant cardiovascular comorbidities including hypertension, tobacco abuse, coronary artery disease, chronic obstructive lung disease, and renal insu ciency 4 .This is of particular interest as the patient being discussed in this case report illustrates someone who falls into multiple categories including age, cardiovascular comorbidities given his history of paroxysmal atrial brillation, previous abdominal aortic aneurysm repair, hyperlipidemia, peripheral vascular disease, and previous tobacco abuse likely resulting in compromised pulmonary function.
We report a case of a 77 year old male with signi cant PMH for paroxysmal atrial brillation (on Xarelto and amiodarone), abdominal aortic aneurysm (AAA) status post repair in 2012, right iliac artery aneurysm status post repair in 2018, chronic obstructive pulmonary disease (COPD), hyperlipidemia (HLD), peripheral vascular disease (PVD), and hypertension (HTN) who presented with a chief complaint of intermittent right-handed weakness.Patient had unrevealing ndings on CT head for acute abnormalities or any hemodynamically signi cant stenosis on carotid US (Fig. 1).Echo revealed severe concentric left ventricular hypertrophy (LVH) and ejection fraction (EF) of 55-60% with moderate diastolic dysfunction (Figs. 2 and 3).CT angiogram of head/neck revealed an irregular mural hypoattentuation of the lateral aspect of the mid to distal ascending aorta and to which contrast extended (Fig. 4).CT angiogram of the chest with and without contrast was then performed which demonstrated contrast extension into the anterior lateral aspect of the ascending thoracic aorta which likely represented a penetrating atheromatous ulcer measuring 0.9 × 0.4 × 1.3 cm with no de nite dissection ap identi ed (Fig. 5).At this point, decision was made to transfer patient to a center of higher level care for further management.
Upon transferring, the patient was evaluated for surgical repair of PAU.Surgery was initially planned for ascending aortic replacement via minimally invasive sternotomy, however given > 6% risk of major adverse cardiac events (MACE), signi cant smoking history, previous AAA rupture repair, and increased risk for surgical complications, more detailed imaging was obtained via CT-TAVR (transaortic valve replacement) with gated technique to rule out change in size of PAU necessitating surgery.This study redemonstrated a focal PAU in the anterolateral ascending thoracic aorta unchanged in size.Left heart catheterization showed non-obstructive coronary artery disease (CAD) with aneurysmal right coronary artery (RCA).Patient was then managed medically and started on dual antiplatelet therapy and high-dose statin with optimization of blood pressure control.Patient was discharged with recommendation to obtain serial CT scans.The rst scan 4 weeks later and a second scan three months later both showed unchanged focal outpouching of ascending aorta concerning for penetrating ulcer.Patient will continue to obtain serial CT scans to monitor progression of ulcer and to determine if a change in size necessitates surgery.

Discussion And Conclusions:
Penetrating aortic ulcers account for 2-7% of acute aortic syndromes, and thus it is crucial to recognize the predisposition of an aortic dissection upon a patient's presentation.Atheromatous ulcers develop in patients with advanced atherosclerosis.Initially, the lesions are con ned to the intimal layer however they can penetrate through elastic intima and into the media.Once a penetrating atheromatous ulcer (PAU) is formed, the ulcer may remain quiescent or progress to acute processes like dissection or aneurysm formation.PAU's also tend to have a scarcity of symptoms which is in contrast to the classic symptoms associated with dissections including severe back or chest pain or aortic regurgitation 5 .Given this patient's risk factors and history of abdominal aortic aneurysm, right iliac artery aneurysm, hypertension, and hyperlipidemia, the threshold for further workup became even lower for this patient.The risk of aortic rupture is signi cantly higher in patients with PAU, and medical management often is ineffective in ascending aortic pathology and surgery is often indicated.Thus, PAUs are considered precursors of lifethreatening aortic dissections, and are rarely located in the ascending aorta.
Life expectancy of patients affected by PAU has not been noted to exceed ten years after diagnosis, which reinstates the severity of disease in these patients 6, 7 .Patients have also been noted to have a concurrent abdominal aortic aneurysm in up to 60% of patients with abdominal PAU 8, 9 .Stanson et.al and Cooke et al. have both illustrated that PAU requires aggressive surgical treatment of symptomatic patients since conservative medical therapy had often times led to recurrence or worsening of symptoms and propensity to rupture 10,11 .An early study by the Yale group found that 40% of patients who were primarily treated conservatively needed emergency interventions for rupture 12 .The Stanford group again demonstrated that progression with PAU occurred in 48% of cases, and a strictly conservative regimen led to 10% mortality within a mean of 9.3 days 3 .These ndings were accepted as the mainstay of treatment unless the risk associated with a patient's comorbidities outweighed the bene t of surgical intervention.These conclusions support the recommendation for surgery.However, in some cases, studies have also shown that many PAU have been managed non-operatively.Hussain et.al argues that a con ned intramural hematoma is not exposed to the turbulent aortic ow that one might nd in a double lumen and thus potentially more likely to remain stable 13 .Kazerooni et.al describes patients with typical symptoms that had abnormal imaging including chest radiograph showing an enlarged thoracic aorta, and CT scans showing intramural hematoma (n = 16), focal ulcer (n = 15), displaced intimal calci cation (n = 13), pleural and/or extrapleural uid (n = 7), mediastinal uid (n = 4), and a thick or enhancing aortic wall (n = 6).The study demonstrated that by comparing lms and treating patients surgically (n = 7) and conservatively (n = 9), eight of the nine patients treated conservatively were asymptomatic after appropriate control of blood pressure 14 .However, it is still important to determine the threshold of an aortic ulcer being present and the verge of it dissecting, which becomes solely surgical when a patient is hemodynamically unstable.
The risk strati cation of the presented patient required serial imaging to quantify the rate of progression, if any, as well as determining the etiology and method of resolution of the patient's right hand weakness.Risk factors for progression are thought to be of various groupings, including simply symptom onset, as well as depth and diameter of PAU.Ganaha et al. identi ed both the maximum PAU diameter and maximum PAU depth (21.1 ± 8.0 mm and 13.7 ± 4.2 mm), as well as rapid increase of aortic diameter and hemodynamic instability as indications for immediate surgery 3 .Given our patient's risk of MACE and comorbidities, it was extremely integral to weigh out advantages and disadvantages.The patient's resolution of symptoms did not necessarily imply lesion stability, and thus it was integral for the patient to have follow up imaging to assess for worsening disease as described above.While the patient was admitted in the intensive care unit (ICU), serial imaging did not show progression of PAU and thus the recommended interval of follow up imaging was prolonged upon discharge from the hospital.The most recent interval for imaging has been prolonged to one year, with most recent CT angiogram of the chest in March 2020 again showing a focal outpouching in ascending thoracic aorta.Patient will return for follow up imaging in March 2021.
If this patient did not have the comorbidities they did, surgical intervention would have prevailed as the primary treatment of choice.Thoracic endovascular aortic repair (TEVAR) is especially effective as an intervention modality.This procedure usually involves a stent delivered through a sheath introduced into the common femoral artery or common iliac artery into the abdominal aorta and further into the level of the thoracic aorta.Brinster et al. showed that this approach in 21 patients all presenting with uncontrolled pain associated with PAU or radiologic evidence of impending rupture, or both.Sixteen of these patients had an acute presentation with symptoms being present for less than fourteen days 15 .All patients treated with endoluminal graft placement had 100% relief of their symptoms with no operative mortalities.This is especially notable since many patients who have previously been managed conservatively often can have disease progression.Conservative management involves adequate blood pressure control with normalization and left ventricular ejection fraction (LVEF) reduction as they are the main determinants of dissection extension and rupture.Beta blockers have been shown to decrease mortality from 67-95% 16 , and for this reason are usually the agents of choice when initiating blood pressure management or titrating medications.
The patient presented in this case report was one of the 5-15% of penetrating aortic ulcers located in the ascending aorta.This is a rare nding, and management remained non-conservative after close following.

Declarations
Ethics approval and consent to participate: Not applicable.Echo revealed severe concentric left ventricular hypertrophy (LVH) and ejection fraction (EF) of 55-60% with moderate diastolic dysfunction Figure 4 CT angiogram of head/neck revealed an irregular mural hypoattentuation of the lateral aspect of the mid to distal ascending aorta and to which contrast extended

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