Fatal and Non-fatal Spontaneous and Iatrogenic Acute Aortic Dissection type A: report of two cases Case

: Aim: To describe iatrogenic and spontaneous presentations of acute aortic dissection (AAD) type A. Method: We report two cases of male patients with iatrogenic non-fatal and spontaneous fatal acute aortic dissection type A. Results: Two male patients are discussed with different aetiology of acute aortic dissection type A. The first patient of 68-years-old, having progressive angina pectoris developed iatrogenic acquired AAD secondary to diagnostic procedure of coronary angiography. Emergent surgical procedure was performed. The second patient of 66-years-old, with known history of aortic dissection type B, presented with acute chest and back pain. The condition was misdiagnosed for acute pulmonary embolism followed by sudden death. Autopsy findings are discussed. Conclusions: Iatrogenic acute aortic dissection type A is a rare complication of routine coronary angiography which requires emergent surgical intervention. Spontaneous AAD may be erroneously seen for acute pulmonary embolism


Introduction: ISSN 2572-102X
Spontaneous Acute Aortic Dissection Type A, Iatrogenic Aortic Dissection Type A, Diagnostic Imaging Technique, Emergent Surgical Intervention.
Acute aortic syndrome (AAS) is classified according to Stanford classification into proximal (type A) and distal (type B) types [1] . AAS encompasses a group of life-threatening type A-and B-aortic conditions (aortic dissection (AD), intramural haematoma (IMH) and penetrating atherosclerotic ulcer (PAU)) that are increasingly recognized due to sophistication, rapid and wide spread application of non-invasive imaging modalities. The syndrome requires high index of clinical suspicion, rapid recognition and appropriate treatment (including operative techniques and cannulation methods) to optimize outcome and improve prognosis [2] . In a recent study, acute AD was initially not suspected in almost one-third of the subjects [3] . Diagnosis is established based on clinical features enforced by rapid imaging techniques and supported by serum biomarkers. Multi-slice computed tomography scanning (MSCT), transthoracic (TTE) and/or Trans oesophageal echocardiography (TEE) or magnetic resonance imaging (MRI) are most common-ly used as the diagnostic imaging technique [2,[4][5][6][7] . Currently, the widely used modality for the initial diagnosis is MSCT [8] . Population-based studies suggest that the incidence of acute AD ranges from 2 to 3.5 cases per 100,000 person-years [2,9] . Type A dissections (AD, IMH and PAU) involve the ascending aorta and in almost all cases require emergent surgical intervention in highly specialized institutes with broad diagnostic and therapeutic facilities [10] and is associated with operative mortality rates up to 35% [11] . Two cases are presented demonstrating iatrogenic non-fatal and spontaneous fatal presentations of the disease.
ing demonstrated silent ischemia. He was treated medically and planned for elective CAG. Routinely right Judkins-4 catheter was used with smooth cannulation of the right coronary artery (RCA). The first projection of the RCA in left anterior oblique position revealed severe atherosclerotic changes (Fig. 1A, black arrow). At the second injection of the RCA in right anterior oblique projection, contrast was directly injected into the aortic wall creating an iatrogenic dissection ( Fig. 1B-D, white arrow). The left coronary artery (Fig. 1E, black arrow) showed diffuse severe obstructive lesions. The patient had no chest or back pain and he was hemodynamically stable. The diagnosis was confirmed by MSCT reveal-ing iatrogenic acute type A-AD (Fig. 1F, white arrow and arrowheads). The patient was immediately sent for emergent operation. At operation, a large entry was found cranial of the RCA ostium and the false lumen was thrombosed. No pericardial effusion was visible. Bio glue was injected between the layers and supra-coronary ascending aorta replacement/repair with 28 Gel weave aorta tubular graft was performed. Coronary artery bypasses grafting with left internal mammary artery to the left anterior descending artery and venous jump graft to the intermediate, obtuse marginal and descending posterior arteries. The post-operative period was uncomplicated.  He was asymptomatic and the blood pressure was well controlled under supervision of his general practitioner. His blood pressure was well managed with a beta blocker, calcium re-entry blocker and statin. He was annually followed-up at the out-patient clinic. On October 17, 2013, at night he was awakened with chest and back pain. He was seen by the paramedics and because of a unchanged appearing ECG, he was reassured and not taken to the hospital. The next morning he was seen by his general practitioner. Due to elevated D-dimer of > 18.000 (normal < 500), suspicion of pulmonary embolism was arisen and he was advised by his general practitioner to consult the pulmonologist. The high sensitivity troponin and NT-proBNP were slightly elevated 21 and 38, respectively. On the way to the hospital he became unconscious and died. At autopsy, the heart weighed 569 gram, cardiac tamponed with thrombus and haemorrhagic fluid filled through type an aortic dissection ( Fig. 2C and D). Pathology specimen of the ascending aorta with spontaneous acute dissection type-A showing C) the dissection (black arrow) with D) mural haematoma and thrombus formation (white arrow). The entire ascending aorta was involved in the dissection reaching the level of the aortic valve leaflets. The coronary and carotid arteries were free of dissection. At the level of the descending thoracic aorta a splitting was found leading to an old and new dissection lumen. The dissection course was from the proximal aorta to the splitting point. The old type B dissection showed an occluded old lumen with a functional pseudo-lumen reaching the iliac arteries. The right kidney was atrophic (40 grams) and left kidney was hypertrophic (299 grams) with a cyst filled with clear yellow fluid. No pulmonary embolism, tumour or infection was found. Myocardial staining demonstrated no recent infarction.

Discussion:
Aortic dissection (AD), first recognized in 1761 [12] and as early as 1802, Maunoir described the process of AD [13] . The incidence of AD is estimated by several authors varying from 2.9/10,000/year [9] to 5-30 per million population/year [14,15] . Aetiology and aetiopathogenesis: (spontaneous, acquired iatrogenic and acquired accidental) Degeneration of the aortic wall, in particular myxoid and mucoid degradation and deterioration of the aortic media layer, has been recognized as an etiologic factor of AD increasing its susceptibility to rupture [16] . AD occurs usually spontaneous [17] but acquired caused by iatrogenic trauma during invasive cardiovascular diagnostic procedure [18] , after coronary surgical intervention [19] and delayed dissection of the donor aorta 22 years following orthotropic heart transplantation [20] have been reported and accounts for 5% of cases [21]. In one of our patients (patient 5), acquired iatrogenic acute AD, without chest or back pain, occurred during diagnostic coronary artery catheterization. Rarely, traumatic chest injury may be incriminated for AD [22,23] . Acquired accidental aorta injuries due to deceleration trauma or blunt chest injury are often involving the descending aorta (type B) [24][25][26] and rarely the ascending aorta [22] . In contrast, as a result of Marfan syndrome AD was detected in the younger patient group (< 70 years) [8] . Meijboom et al reported that pregnancy in Marfan syndrome is relatively safe up to an aortic root diameter of 45 mm [27] . Few cases, with successful repair, have been reported describing acute aortic dissection which may rarely occur especially during the third trimester of pregnancy in Marfan patients. These cases had an aortic root dilatation of 60 and 52 mm, respectively [28,29] . Clinical presentation and differential diagnosis: AD is an infrequent but highly fatal disorder which is associated initially with acute chest pain in 92-96% and without chest pain in 4-8% of patients [9,30] . In our first case, the acquired iatrogenic AD was painless. Earlier reports have elucidated that one-third of cases were initially missed [31] and that AD was clinically suspected only in 15% of patients before death [9] . Although infrequent, AD should enter into the differential diagnosis of patients either presenting with acute chest pain associated with or without arterial hypertension and/or aortic regurgitation or mimicking ST-segment elevation myocardial infarction [21,32] . AD should be differentiated from acute pulmonary embolism and acute coronary syndromes [32] . Mehta et al., reported that acute type A-AD as a result of hypertension, atherosclerosis and iatrogenic post cardiac surgery, were commonly found in the elderly (>70 years) [8] .

Diagnostic modalities:
Multi-slice computed tomography scanning (MSCT), transthoracic (TTE) and/or Trans oesophageal echocardiography (TEE) or magnetic resonance imaging (MRI) are most commonly used as the diagnostic imaging technique [2,[4][5][6][7] . Recently, the widely used modality for the initial diagnosis is MSCT [8] . It is emphasized that high index of clinical suspicion and early imaging studies (MSCT and/or TEE) may lead to early recognition and hence proper timely surgical intervention to improve outcome and prognosis. Recently, using 32-slice MSCT scanning, a false diagnosis of type A-AD in a pregnant woman having a normal aorta has been reported [33] . Electrocardiography: In the series of Evangelista et al., normal ECG without ST-T segment changes was found in 38% of patients [30] . ECG demonstrated evidence of acute myocardial infarction in 5% of patients with type A-AD [21] . On the other hand, ECG with acute coronary syndrome-resembling electrocardiographic profiles were described in approximately 25% of patients which was associated with more complications and in type A-AD was an independent predictor of in-hospital mortality [6] . In addition, a normal ECG can increase the suspicion of the occurrence of AD. The initial ECG in our patients showed either normal or non-diagnostic findings, such as nonspecific ST segment abnormalities, sinus bradycardia or sinus tachycardia and voltage criteria for left ventricular hypertrophy. Chest x-ray: It was demonstrated in two large series that the chest x-ray was normal in 10-20% of the cases [21,30] and mediastina widening was observed more frequently in type A than type B-AD (58% vs. 43%) [30] . A normal chest x-ray is not capable of ruling out the suspicion of AD. Biomarkers: Recently, from our group, Linssen et al. demonstrated that plasma N-terminal pro-Brain-type natriuretic peptide (NT-proBNP) independently predicted all-cause mortality and cardiovascular events in the general population [34] . In contrast to C-reactive protein (CRP), BNP is a marker of specific pathophysiological processes, especially in relation to ventricular dysfunction and ischemic burden [35]. Many supplementary biomarkers (CRP, D-dimer, NT-proBNP) could be helpful in early diagnosis and rapid classification of acute chest pain guiding management and predicting the prognosis [36] . In a recent retrospective study by Sakamoto et al., they suggested that a cut-off value of 5.0 µg/ml of D-dimer could differentiate between AD and pulmonary embolism from acute myocardial infarction [37] . They recommended to perform MSCT first in a patient with D-dimer value > 5.0 µg/ml [37] to rule out AD. C-Reactive Protein values were demonstrated to have positive correlation with aortic diameter (> 48 mm) and age (> 65 years) in predicting in-hospital development of clinical events and mortality [38] . All available conventional biomarkers are nonspecific and should be used with caution for differentiation between chest pain syndromes (acute aortic syndrome, acute coronary syndrome and pulmonary embolism), in conclusion, there is yet no a reliable biomarker readily available to differentiate between the different acute chest pain syndromes [39] . Elevated D-dimer may justify urgent contrast enhanced MSCT scanning to differentiate between the different acute aortic, coronary or pulmonary vascular syndromes. Mortality: Acute type A-AD is highly fatal disorder with an early mortality of 1-2% per hour. The published in-hospital mortality rate of spontaneous AD was 22.1% [18] . Iatrogenic AD is associated with higher mortality rate than spontaneous AD (35% vs. 24%) [21,40,41] . Among the predictors for early mortality are aortic diameter of > 50 mm and involvement of ascending aorta [5] . Acute coronary syndrome-like ECG finding could raise the possibility of misdiagnosis and in type A-AD it was, besides syncope at presentation and advanced age, a strong independent predictor of in-hospital mortality [6] . Vanhuyse et al., reported higher operative mortality rate of 40% in patients aged > 80 years compared to 18% in patients aged < 80 years [42] . On the other hand, Kawahito et al., observed no significant differences in the hospital mortality, actuarial survival or event free rates of surgically treated patients, for type A-AD, aged more than 75 or less than 75 years [43] . Hospital mortality rates varied from 10.5% (<75 years) to 13.0% (> 75 years) [43] and overall rate of 13.4% in a population with a mean age of 60 years [44] . Acute type A-AD accounts for 14% of maternal cardiac mortalities in the United Kingdom [45] . In 2000, in the autopsy series (84 patients with 86 AD) of Meszaros et al., in only 13 patients (13/84=15%), AD was clinically suspected before death. Aortic dissection was proven at autopsy in 80/84 (95%), by surgical procedure in 6/84 (7%) and by ultrasound and MSCT scan in 2/84 (2.4%) of patients who remained alive [9] . Post-mortem, atherosclerosis of the aorta and ostial stenosis of the coronary arteries were found in (11/80=14%) and (76/80=95%), respectively. Finally, rupture of the aorta causing death was detected in (69/86=80%) of patients [9] . In a single-centre prospective study, it was found that in-hospital mortality was significantly associated with elevated D-dimer, CRP and aortic diameter [46] .

Conclusions:
Iatrogenic acute aortic dissection type A is a rare complication of routine coronary angiography which requires emergent surgical intervention. Spontaneous acute type A-AD may be erroneously seen for acute pulmonary embolism.