a b s t r a c t

Background: Stanford Type A Aortic Dissection may lead to Coronary artery occlusion and malfunction. However, TAAD manifesting as acute ST-segment elevation myocardial infarction has not been studied. In the present study, we reported 8 TAAD cases with STEMI as the Primary presentation, and analyzed their clin- ical characteristics and outcome.

Methods: The records were reviewed for patients admitted to the large comprehensive university hospital for PCI due to STEMI from January 1, 2002 to January 1, 2017.

Results: The incidence of STEMI secondary to TAAD in our center was 0.51% (8/1,576). A total of 5 patients underwent urgent Coronary angiography without awareness of TAAD. Compression at the ostium of right coronary artery was found in 2 patients, dissected flap of RCA in 1 patient, and heterogeneous filling and false lumen in RCA in 1 patient. Three of these 5 patients received surgery and survived. One patient accepted urgent RCA stenting because of cardiogenic shock and died after refusal of surgical therapy and failure of medical treatment. Another 2 patients received thrombolytic therapy died prior to CAG. Thus, the total in-hospital mor- tality was 37.5% (3/8).

Conclusions: TAAD presenting as STEMI was a Rare condition that predominantly involved RCA. A quick and cor- rect clinical diagnosis of STEMI caused by TAAD prior to invasive procedure would be important. Urgent CAG without awareness of TAAD could provide important information for a Timely diagnosis. High level of suspicion and awareness is the key to establishing the diagnosis and achieving optimal clinical outcome.

(C) 2017

Introduction

Aortic dissection (AD) is a life-threatening vascular lesion that is not easily detectable until an acute and often catastrophic complication oc- curs [1,2]. When the Stanford type A aortic dissection (TAAD) extends to the coronary artery (either due to tear of the vessel wall or hematoma compression), a complete acute coronary occlusion may occur, leading to ST-segment elevation myocardial infarction [1-5].

The diagnosis of STEMI secondary to TAAD is challenging, and could be easily misdiagnosed as the uncomplicated regular STEMI. Chest pain, which is similar to STEMI, is more commonly associated with Type A AD than type B AD. Von Kodolitsch and colleagues [6] introduced a model for the initial prediction of AD based on three variables (acute aortic pain, mediastinal widening and/or aortic widening, pulse and/or blood

* Corresponding author at: Department of Cardiology, The Second Xiangya Hospital of Central South University, 139 middle Ren-min road, Changsha, Hunan 410011, China.

E-mail address: [email protected] (X. Hu).

pressure differentials). Careful assessment of the three variables could identify 96% of acute aortic dissection cases. However, these typical clin- ical and radiographic findings might not always be present for every pa- tient with AD. Therefore, other diagnostic modalities like D-dimer and computed tomography (CT) could be important to establish the diagno- sis of typical AD [7]. However, the imaging studies for STEMI patients may not be done initially because it could increase the “door to balloon” time in the emergency setting.

Primary percutaneous coronary intervention is of great impor- tance for STEMI patients to re-establish the Coronary blood flow quickly and effectively. However, PCI may delay the preparation for the surgery for TAAD patients. On the other hand, prompt coronary revasculariza- tion could provide the TAAD patients the critical time for the prepara- tion for the surgical treatment. If the patients were sent to a hospital without PCI capability, these patients could very likely receive throm- bolysis for STEMI with potential Catastrophic outcome. It is very difficult to make the correct and timely diagnosis for the TAAD patients who present with STEMI, and the appropriate management for these

http://dx.doi.org/10.1016/j.ajem.2017.05.010

0735-6757/(C) 2017

patients remains challenging and even controversial. In the present study, we summarized the data and clinical characteristics as well as the outcome for 8 TAAD patients with the initial manifestation as STEMI.

Methods

Patients

The research protocol of the present study was reviewed and ap- proved by the Medical Ethics Committee of the Second Xiangya Hospital of Central South University in Changsha, China. The records were reviewed for patients admitted to the large comprehensive university hospital (with over 3500 licensed beds) for PCI due to STEMI from Jan- uary 1, 2002 to January 1, 2017(Fig. 1.) All of the patients were sent from the emergency department (ED) when they were diagnosed with STEMI by ED physicians. The diagnosis of STEMI was based on the latest criteria established by the American College of Cardiology and European Society of Cardiology, including chest pain lasting for more than 30 min, persistent ST-segment elevation (>= 0.1 mV in limb leads or >= 0.2 mV in precordial leads) in at least two contiguous leads on a 12-lead electro- cardiogram (ECG), and an increase of cardiac biomarker values [prefer- ably cardiac troponin (cTn)] with at least one value above the 99th percentile of the Upper reference limit [8]. The patients were then urgently evaluated by interventional cardiologists to determine if a PCI was needed. If clinically indicated, the patients were sent to the catheterization lab for urgent cardiac catheterization and PCI if needed. All the patients’ data were recorded electronically in the hospital and in the catheterization lab. All the patients with the final diagnosis of TAAD were included and analyzed in the present study. Patients with TAAD who were diagnosed as STEMI initially were identified retrospectively when the diagnosis of TAAD was established with clinical presentation, diagnostic modalities including cardiac catheterization and imaging studies, and coronary angiography (CAG) findings. TAAD was diagnosed when the lesion involved the Ascending aorta and arch, and was proxi- mal to the left subclavian artery as described [9].

The CAG imaging was characterized and analyzed in the patients with STEMI in the setting of acute TAAD, and evaluated for Primary PCI as described previously [5,10-16]. A thorough English-language lit- erature search was performed through PubMed for any study on AD with specific focus on the studies regarding coronary artery occlusion from AD. The data from the present study were compared with the pub- lished data in terms of patient demographics, management, and outcomes.

Fig. 1. STEMI: ST-segment elevation myocardial infarction; ER: Emergency Room; Cath Lab: Catheterization Lab; CXR: Chest radiography; TTE: Transthoracic Echocardiography; CAG: coronary angiography; CT: Contrast computed tomographic scan.

Statistical analysis

Continuous variables were presented as mean and standard devia- tion (SD) or median (range), depending on whether the data were nor- mally distributed. Categorical variables were presented as frequencies and percentages. The data were unable to be analyzed statistically due to the small size of patient population that was clearly a major limitation of the present study.

Results

A total of 1576 patients were admitted to the large university hospi- tal with STEMI for primary PCI between January 1st, 2002 and January 1st, 2017. Only 8 patients (0.51%, 4 males and 4 females with their ages from 40 to 84 and average of 57.5 years old) were finally diagnosed with TAAD. The clinical characteristics of these 8 patients were summa- rized in Table 1. Anterior chest pain was the initial presenting symptom for all 8 patients. Two patients also suffered from back pain, and were found that their dissections were extended to the descending aorta. There was no history of Marfan syndrome, coronary artery diseases, prior AD or aneurysm or prior cardiac surgery in these patients. One woman had hemodynamic instability, and received an intra-aortic bal- loon pump (IABP) before CAG.

In the 8 patients, physical examination revealed diastolic heart mur- murs in the third intercostal space at the left sternal border after admis- sion in 2 patients (case1 and case2) before CAG and a bedside Transthoracic echocardiography revealed intimal flaps in the as- cending aorta. The chest radiography of case 7 showed widened medi- astinum, and her TTE showed ascending aortic dilatation prior to catheterization. Thus, Computed tomography angiography was performed and confirmed the diagnosis of TAAD. The diagnostic evalu- ations of all 8 cases were summarized in Table 2. Of note, CAG findings were only suggestive of the presence of TAAD, but not considered diag- nostic for TAAD. Thus, a confirmative imaging studies especially Chest CT scan with contrast were used to establish the diagnosis.

The other 5 patients underwent urgent CAG without awareness of TAAD. All these 5 patients had right coronary artery involvement. An extrinsic compression at the RCA ostium was found in 2 patients (cases 3 and 5), and an intimal flap at the RCA ostium in one patient (case 4) (Fig. 2A and B). Aortography (case 3, 5) and CT imaging con- firmed the presence of TAAD in the 2 patients with RCA ostium com- pression (cases 3 and 5). Complete obstruction at the RCA ostium was seen in a male patient (case 6). His aortography did not show the pa- thology; however, a CTA clearly identified a horizontal tear of the right coronary sinus (Fig. 3). The case 8 was a male patient, whose CAG showed heterogeneous filling of the RCA with many parts supplied by the false lumen. During the procedure, it was noticed that he had no pulse in the lower limb. An urgent CTA demonstrated that his dissection had extended to the iliac arteries.

Table 1

Clinical Characteristics of the Patients with TAAD Presenting as STEMI

Patient	Age (year)	Sex	Hypertension (years)	Smoking	Chest pain	Back pain	Cardiogenic shock
1	40	F	+(2)	-	+	-	-
2	55	F	+(8)	+(480)	+	-	-
3	56	M	+(11)	+(400)	+	-	-
4	52	M	+(26)	+(1200)	+	-	-
5	74	F	-	-	+	-	+
6	60	M	+(4)	+(1200)	+	+	-
7	84	F	-	-	+	-	-
8	59	M	+(10)	+(400)	+	+	-
		50%	75%	62.5%	100%	25%	12.5%

STEMI: ST-segment elevation myocardial infarction; TAAD: Type A aortic dissection; CAD: Coronary artery disease; F:Female, M:Male;smoking index = cigarettes number per day multiply smoking years;

Table 2

Diagnostic Evaluations, Managements and Outcomes

Patient no.	CXR	TTE prior to CAG	AO diameter (mm)	CAG	Diagnosis before CAG	Involved vessel	Aortography	CT	Thrombolysis therapy	Stenting	Surgery	Outcome
1	+	+	54	+	+	RCA	NA	+	+	-	+	Alive
2	+	+	36	+	-	RCA	NA	+	+	-	-	Deceased
3	+	-	41	+	-	RCA	+	+	-	-	+	Alive
4	+	-	45	+	-	RCA	-	+	-	-	+	Alive
5	-	-	37	+	-	RCA	+	+	-	+	-	Deceased
6	-	+	39	+	-	RCA	+	+	-	-	+	Alive
7	+	-	45	-	+	NA	-	+	-	-	-	Alive
8	+	+	49	+	-	RCA	-	+	+	-	-	Deceased

CXR: Chest radiography; TTE: Transthoracic echocardiography; AO: TTE shows aortic root dimension (mm): normal value 20-35 mm;CAG: Coronary angiography; RCA: Right coronary artery; NA: not available; CT: Contrast computed tomographic scan.

Thrombolytic therapy was given to 3 patients (cases 1, 2, and 8) at local hospitals before transferring to our hospital for PCI. One patient (case 1) received emergency surgery (Bentall Procedure) and survived, while the other two patients (cases 2 and 8) died before CAG. Another patient (case 5) developed cardiogenic shock at ED, and received urgent RCA stenting with the support of IABP. This patient subsequently died shortly after the stenting when medical therapy failed and urgent sur- gery was refused by the patient. Case 3 and case 4 were treated with surgery and survived. Case 7 refused surgery because of old age (84 years). Therefore, the total in-hospital mortality for the patients with TAAD presenting as STEMI was 37.5% (3/8). The clinical data and the outcomes of all 8 patients were summarized in Table 2.

Discussion

The incidence of acute myocardial ischemia and infarction second- ary to type A aortic dissection (TAAD) ranges from 5.7% to 11.3% due to retrograde dissection of the aortic root reaching the coronary ostia [1-4]. Approximately 2.5% of patients with TAAD present with STEMI on ECG [5]. The incidence in our catheterization lab was 8/1576 (0.51%) with the mortality rate 37.5% (3/8) that was compatible with the findings from previous studies (20-36%) [4,5].

The mortality associated with Acute aortic dissection is high

at an estimated rate of 1% to 2% per hour immediately after symptom onset in untreated patients [2,19,20]. The International Registry of Acute Aortic Dissection (IRAD) has identified many factors that may delay the diagnosis and definitive treatment of AAD. It is important to point out that increased physician awareness of atypical presentations of AAD could reduce the crucial time to establish the diagnosis [21]. In the non-primary PCI-capable hospitals, the management of STEMI

caused by TAAD could be very challenging due to the urgent nature of the condition and limited diagnostic and treatment options. In most cases, the patients received a thrombolytic therapy when STEMI was di- agnosed. A timely thrombolysis could be a life-saving therapy for the majority of non-complicated STEMI patients. However, it could be cata- strophic for the patients with TAAD presenting as STEMI just like some of the patients in the present study (case 1,2,8). Unfortunately, there is no optimal strategy to identify and diagnose the patients with TAAD who present as STEMI. To distinguish STEMI caused by TAAD from ath- erosclerotic etiology, a bedside TTE is probably the most economical and feasible modality in an emergency setting [5]. In our case 1 and 2, TTE was of great importance. Based on previous studies [5,22], there are three important clues for the presence of TAAD including aortic root di- lation, aortic eccentric regurgitation, and pericardial effusion, as we ob- served in the patient case 7 with the TTE. Thus, if available, an urgent Bedside echocardiography is recommended.

When TAAD is suspected, an emergency chest CT scanning is of great value to establish the diagnosis quickly due to its good imaging for the aorta and coronary anatomy. However, if there are no signs and symp- toms suggesting TAAD clinically, a chest CT is of little value with low yield since more than 99% of STEMI is atherosclerotic in nature [5,23]. In primary PCI-capable hospitals, obtaining a CT imaging could delay the reperfusion therapy. In the present study, 7 patients underwent ur- gent CAG without awareness of TAAD. Confirmative imaging (aortogra- phy and/or chest CT) were obtained to establish the diagnosis only when the CAG findings were suspicious of TAAD as described in the “Re- sults” section. Clinical data including age and sex as well as history of hypertension (HTN) or aortic root diameter were not helpful on predicting the presence of TAAD since the patients with TAAD in the present study included both male and female with a wide age range.

Fig. 2. (A). Right coronary angiography (Left Anterior Oblique Projection) revealed an intimal flap (white arrow) at the proximal portion, with a TIMI 3 flow distally. (B). Cranial Projection also showed an intimal flap (white arrow) at the proximal portion of right coronary artery.

Fig. 3. Coronary artery in a three-dimensional reconstruction (white arrow) showed the dissection rupture narrowing the ostium of right coronary artery.

Some of the patients who had TAAD and presented as STEMI had no his- tory of HTN or dilated aortic roots. STEMI caused by TAAD or atheroscle- rotic plaque share similar risk factors including hypertension [7,8]and aging [17]. It was certainly possible that some STEMI cases with TAAD might have been missed or unrecognized during CAG. Clearly, a high level of suspicion and awareness is the key to the timely diagnosis and effective therapy for this special group of patients. During a cardiac cath- eterization procedure, an intravascular ultrasound (IVUS) examination could quickly reveal the presence of TAAD in STEMI patients as reported by Na and associates [11].

The overall mortality for the patients with STEMI in our hospital is consistent with published data. More case of TAAD might be discovered

if an autopsy was performed to establish the cause(s) for the mortality for the patients with STEMI. Unfortunately, very few post-mortem au- topsy was granted by the family or requested until an unusual cause of death was strongly suspected. It could be very intriguing and clinical- ly important to determine how much the accompanying TAAD could contribute to the mortality for the patients with STEMI in view of the high mortality associated with TAAD. If the condition (STEMI caused by TAAD) were able to be identified early, the mortality associated with STEMI could be further reduced significantly. A specific clinical study is needed to achieve the goal that is clearly beyond the scope of the present study.

Currently, the treatment of STEMI caused by TAAD is not standard- ized or even controversial because of the low incidence and lack of data from reliable large clinical studies. The current guidelines have sug- gested surgical resection and replacement of the thoracic aorta as the gold standard for the treatment of TAAD [1,2,9]. However, a direct stenting could be important to stabilize the patient before surgery, [24], just like one of the patients in the present study (case 5). Thus, the management of STEMI caused by TAAD should be individualized. Stable patients should undergo corrective surgery directly, while unsta- ble patients may benefit from an initial coronary stenting before sur- gery. This approach was supported with the outcome from previously reported cases [5,10-16] as summarized in Table 3. In the reported 8 pa- tients, 7 underwent emergency CAG without awareness of TAAD, the other patient was suspected to have STEMI due to TAAD before primary PCI because of a history of TAAD. All the 8 patients with acute myocar- dial infarction due to TAAD (6 with cardiogenic shock) received coro- nary stenting before surgery, and 6 patients survived, while patient F died after surgery. The outcome information was not available for one patient B. These data demonstrated the value and benefit of stenting the collapsed coronary artery as a potential lifesaving modality and a bridge to corrective surgery. However, a controlled clinical study with reasonable size of patient population is needed to confirm and develop the optimal management strategy for the patients with TAAD present- ing as STEMI.

It is known that RCA is more commonly involved than the left coro- nary artery in the setting of TAAD, manifesting as an acute inferior myo- cardial infarction [4,18]. We noticed that the involved coronary artery associated with TAAD was RCA for all the 8 patients in the present study. It was of great interest to note that in the reported 8 cases, RCA was founded to be the vessel involved in all the patients from the re- gions in Asian including Japan, Taiwen, and South Korea, while left main coronary artery (LM) was the one that was compromised fre- quently in the patients from Western countries like Canada, the Nether- lands, Italy, and Australia [10,12,15]. The reason(s) for the difference in the involved coronary arteries in the setting of TAAD among the differ- ent populations was unclear. The difference appeared to be associated with the patients’ ethnic backgrounds (Asian vs non-Asian). A large study with adequate patient populations from different ethnic

Table 3

Clinical Characteristics of STEMI due to TAAD in Patients with Stenting in the Literature

Patient	Age (year)	Sex	Cardiogenic Shock	Diagnosis before/after CAG	Cardiac catherization findings	Involved vessel	Diagnostic modality	Outcome	Ethnic group	Reference
A	74	M	-	After	Enlarged mediastinm, LM	LM	TTE	Alive	Canada	[10]
B	69	M	+	After	heterogeneous filling Intimal flap at mid-portion	RCA	IVUS	NA	Korea	[11]
C	52	F	+	After	LM compression	LM	TTE	Alive	Netherlands	[12]
D	67	F	+	After	Proximal RCA compression	RCA	TTE	Alive	Korea	[13]
E	63	F	NA	After	NA	RCA	Aortography	Alive	China	[5]
F	71	F	+	Before	Intimal flap of proximal RCA	RCA	CT	Died	Japan	[14]
G	56	M	+	After	Enlarged mediastinm, LM compression	LM	Aortography	Alive	Australia	[15]
H	70	M	+	After	LM compression	LM	Aortography	Alive	Italy	[16]

STEMI: ST-segment elevation myocardial infarction; TAAD: Type A aortic dissection; TTE: Transthoracic echocardiography; CAG: Coronary angiography; IVUS: Intravascular ultrasound; NA: not available; CT: Contrast computed tomographic scan; LM: Left Main coronary artery; RCA: Right coronary artery.

background with this condition is needed to verify the finding from the present study.

Conclusion

In summary, STEMI caused by TAAD is a rare, but fatal emergency condition. There seemed to be a difference in the involved arteries in the patients with different ethnic background. It is not productive to screen all the patients with STEMI for TAAD. High level of suspicion and awareness is the key to establish the diagnosis and achieve the op- timal clinical outcome. This fatal condition needs to be ruled out and managed accordingly in the presence of cardiac murmurs, enlarged me- diastinum, aortic eccentric regurgitation, and history of TAAD. If emer- gency CAG is performed without awareness of TAAD, findings like extrinsic compression and intimal flap at the coronary artery especially RCA in Asia population could be a strong indication for further evalua- tion for TAAD.

Funding

This work was supported by a grant from Hunan Provincial Science and Technology Department (No: 2015SF2045-4).

Conflict of interest

None declared.

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