Risk analysis and improvement of strategies in patients who have acute type A aortic dissection with coronary artery dissection^†

Abstract

OBJECTIVES

To identify the risk factors for mortality and establish improved treatment strategies in patients who have acute type A aortic dissection with coronary artery dissection.

METHODS

From January 1994 through December 2011, we performed surgery in 516 patients with acute type A aortic dissection. We studied 75 (15%) of these patients who had coronary artery dissection. Myocardial ischaemia was present in 48 (64%) of the 75 patients. The culprit coronary artery was the right coronary artery (RCA) in 26 patients, the left coronary artery (LCA) in 19 and the RCA + LCA in 3. For coronary artery reconstruction, preoperative coronary stent placement was done in 7 patients (RCA, 4 and LCA, 3), aortic root replacement in 14, coronary artery bypass grafting in 23 and biological glue application in 28. The relationships of preoperative risk factors and coronary artery reconstruction procedure with in-hospital death and postoperative low cardiac output syndrome (LOS) were analysed using Fisher's exact test.

RESULTS

Hospital death was 18/75 patients (24%), 16/48 (33%) among patients with ischaemia and 2/27 (7.4%) without ischaemia. The culprit lesion involved the RCA in 4/26 patients (15%), the LCA in 9/19 (47%) and the RCA + LCA in 3/3 (100%). Factors related to operative mortality were ischaemia (P = 0.019), LCA territory ischaemia (P = 0.003) and preoperative cardiopulmonary arrest (CPA) (P = 0.013). Postoperative LOS was less common in patients with coronary stent placement (P = 0.042).

CONCLUSIONS

In patients who undergo surgery for acute type A dissection with coronary artery dissection, preoperative CPA and myocardial ischaemia (particularly LCA territory ischaemia) negatively affect survival outcomes. Early revascularization by coronary stent placement is effective in preventing postoperative LOS.

INTRODUCTION

Type A aortic dissection with coronary artery dissection is a serious, potentially lethal condition associated with a high risk of acute myocardial infarction caused by acutely impaired coronary blood flow. Myocardial ischaemia due to coronary artery dissection develops in 5.7–11.3% of patients with acute type A aortic dissection [1–3]. Because the numbers of patients reported in past articles were small (range 12–24), many points remain unclear, including the incidence of myocardial ischaemia associated with coronary artery dissection, the principal sites of coronary artery dissection, differences among dissection types and the effects of coronary angioplasty on outcomes. We studied (i) the presence or absence of myocardial ischaemia, (ii) the sites of coronary artery dissection, (iii) dissection patterns and (iv) the effects of factors such as preoperative shock, cardiopulmonary arrest (CPA) and cardiac tamponade on the rates of circulatory failure and operative mortality in 75 patients with coronary artery dissection. We also investigated strategies for improving treatment outcomes.

METHODS

Patients

From January 1994 through December 2011, we performed surgery in 516 patients with acute type A aortic dissection. We studied 75 (15%) of these patients in whom coronary artery dissection involving the ostium was confirmed on intraoperative examination, coronary angiography or transoesophageal echocardiography. Two other patients who concurrently had chronic coronary artery disease were excluded because of difficulty in distinguishing whether ischaemia was caused by chronic coronary artery stenosis or by coronary artery dissection with aortic dissection. There were 35 men and 40 women. Their mean age was 60.8 ± 12.2 years. The median time from symptom onset to surgery was 6.3 h (range 22.7 ± 47.6). Their clinical backgrounds are given in Table 1. Background factors included hypertension in 67% (50/75) of the patients and preoperative coronary angiography in 24% (18/75). Preoperative complications at presentation are given in Table 2. Complications included shock (systolic blood pressure, <80 mmHg) in 36% of the patients and CPA in 13%. The median perioperative peak creatine kinase level was 2346 IU/l (range, 3828 ± 4616), and the median perioperative peak creatine kinase MB level was 77 IU/l (range, 145 ± 191).

Dissections involved the right coronary artery (RCA) in 43 patients, the left coronary artery (LCA) in 18 and the RCA + LCA in 14. The RCA was thus most often involved. Intimal detachment was present in 9 patients with RCA dissection, but was not found in those with LCA dissection.

Acute myocardial ischaemia or infarction associated with coronary artery dissection was defined as preoperative or intraoperative ischaemic ST-T changes or abnormal Q waves on electrocardiography or distinctly decreased wall motion at the territory affected by coronary artery dissection on echocardiography. Ischaemia occurred in 64% (48/75) of the patients. In 15% (7/48) of these patients, myocardial ischaemia associated with decreased left ventricular motion occurred at the time of weaning from the heart–lung machine after aortic repair. Overall, 83% (40/48) of the patients with ischaemia had electrocardiographic abnormalities, and 81% (39/48) had decreases in regional wall motion. The culprit coronary arteries in the ischaemic region were the RCA in 26 patients, the LCA in 19 and the RCA + LCA in 3.

Written informed consent was obtained from all subjects of this study. Since 1994, diagnosis has been made on computed tomographic scanning in principle, and preoperative angiography was not performed.

Operative procedures

The procedures used to manage dissections of the ascending aorta and aortic arch were ascending aortic replacement in 53 patients, total arch replacement in 13, hemiarch replacement in 8 and stent-graft closure of the descending aortic entry in 1 patient with retrograde ascending aortic dissection.

Since 1997, a coronary stent has been placed in the left main trunk in the cardiac catheterization laboratory in patients with LCA dissection; aortic repair was then performed. In patients with RCA dissection, aortic repair was directly performed, in principle. However, if type A aortic dissection and RCA dissection were diagnosed in the cardiac catheterization laboratory, a stent was placed in the RCA before operation. In 7 patients who preoperatively had myocardial ischaemia, stents were placed in the dissected artery and the true lumen was expanded to achieve early improvement of ischaemia (RCA in 4 patients and LCA in 3). At the time of stent placement, the balloon was inflated to below the nominal pressure to avoid injury to the intima. In 2 of the patients with preoperative myocardial ischaemia, coronary artery bypass grafting (CABG) was additionally performed during surgery.

CABG with the use of saphenous vein grafts was performed in 23 patients (RCA in 12, LCA in10 and RCA + LCA in 1).

Aortic-root reconstruction was performed in 14 patients who had entry or rupture sites in the aortic root (Bentall procedure in 11 and reimplantation in 3). In 12 patients who underwent aortic-root reconstruction, a synthetic graft was directly anastomosed to the coronary artery. (In 3 patients, the origin of the RCA was resected along with the dissection, and the graft was directly anastomosed to the non-involved segment.) One patient underwent direct anastomosis to the RCA, resection of the dissected main trunk of the LCA and repair with a superficial femoral artery interposition graft. Another patient underwent reconstruction by CABG with a saphenous vein graft.

Since 1995, gelatin-resorcin-formaldehyde (GRF) glue has been used to obliterate the false lumen in the aortic root or to promote adhesion of tissue around the coronary arteries in patients with dissection limited to the coronary ostia, with no entry or rupture site in the aortic root. Since 2004, fibrin glue has similarly been used (GRF glue, 16 patients; fibrin glue, 12).

The proximal false lumen was closed with mattress sutures buttressed with Teflon felt in 3 patients. No special techniques were used for coronary artery reconstruction.

Cerebral protection was performed at the time of operation in 74 patients, excluding 1 patient who underwent stent grafting. The procedure used was hypothermia plus circulatory arrest in 19 patients (1994–1998), hypothermia plus retrograde cerebral perfusion in 33 (1998–2008) and selective cerebral perfusion in 22 (2008–2011).

To arrest the heart, cardioplegia was accomplished with infusion of a mixture of blood from the heart–lung machine and St. Thomas' Hospital solution cooled to 20°C. Antegrade ostial perfusion was performed in 12 patients, retrograde coronary sinus perfusion was done in 9, and since 1999, both techniques have been used in 53 patients (72%).

Statistical analysis

Effects of the presence or absence of ischaemia, the culprit coronary artery and the site of dissection on the occurrence of preoperative shock and CPA were studied (Fisher's exact test).

Fisher's exact test and the Wilcoxon test were used to evaluate the effects of the following variables on in-hospital death and postoperative low cardiac output syndrome (LOS): the presence or absence of ischaemia, dissection site (RCA, LCA or RCA + LCA), culprit coronary artery responsible for ischaemia (RCA, LCA or RCA + LCA), the preoperative risk factors of shock and CPA, cardiac tamponade, aortic regurgitation of >Grade II, perioperative peak creatine kinase levels and perioperative peak creatine kinase MB levels. Coronary stent placement and different reconstruction procedures were performed to reduce myocardial infarct size. Fisher's exact test was used to compare postoperative survival rates and postoperative LOS-free rates between patients undergoing revascularization by different procedures, particularly preoperative coronary stent placement to minimize infarct size and other patients. Postoperative LOS was diagnosed in 2 patients who could not be weaned off the heart–lung machine because of circulatory failure, 8 patients in whom weaning was enabled by percutaneous cardiopulmonary support and 10 patients who had a postoperative cardiac index of <2.0 l/min/m² and required catecholamine support for at least 1 week after surgery.

RESULTS

The incidence of myocardial ischaemia according to the involved coronary artery was 49% (28/57) for the RCA and 69% (22/32) for the LCA.

The incidence of preoperative shock was 40% (19/48) in the myocardial ischaemia group and 30% (8/27) in the non-myocardial ischaemia group. This difference was not significant (P = 0.611). The incidence of preoperative CPA was significantly higher in the myocardial ischaemia group (21%) than in the non-myocardial ischaemia group (0%) (Table 3). In the myocardial ischaemia group, the incidence of preoperative shock according to the site of ischaemic culprit lesions was 38% (10/26) for the RCA, 47% (9/19) for the LCA and 0% (0/3) for the RCA + LCA. These differences were not significant (P = 0.427). However, the incidence of preoperative CPA was significantly higher in the LCA group than in the RCA group and RCA + LCA group. As for the dissection site, the LCA was associated with a significantly higher incidence of preoperative CPA (Table 3).

The in-hospital mortality rate was 24% (18/75). The cause of death was LOS in 13 patients, multiple organ dysfunction in 2, postoperative sudden ventricular fibrillation in 1, bleeding in 1 and cardiac arrest due to postoperative subacute thrombosis in 1. In this latter patient, antiplatelet therapy after coronary stent placement was discontinued because of postoperative gastrointestinal bleeding. There were no complications related to the technique used for stent placement.

In-hospital mortality was significantly higher in ischaemic (33%) than non-ischaemic patients (7%). The in-hospital mortality rate according to the culprit artery in the ischaemic patients was 17% for the RCA, 47% for the LCA and 100% for the RCA + LCA. Postoperative in-hospital death was significantly related to the presence of ischaemia, the presence of LCA territory ischaemia, and preoperative CPA. In contrast, postoperative in-hospital death was not significantly related to LCA dissection, shock, cardiac tamponade, aortic regurgitation of >Grade II (Table 4), perioperative peak creatine kinase levels (P = 0.487) or perioperative peak creatine kinase MB levels (P = 0.080, Wilcoxon test).

Postoperative LOS was significantly related to the presence of ischaemia, the presence of LCA territory ischaemia, LCA dissection and preoperative CPA, but was not significantly related to shock, cardiac tamponade, aortic regurgitation of >Grade II (Table 5), perioperative peak creatine kinase levels (P = 0.755) or perioperative peak creatine kinase MB levels (P = 0.293, Wilcoxon test). In patients with coronary ischaemia, mortality rates did not differ according to the procedure used for coronary angioplasty (Table 6). However, the incidence of postoperative LOS was significantly lower in patients who underwent coronary stent placement (Table 7).

DISCUSSION

Spittell et al. [4] reported that the incidence of RCA dissection was higher than that of LCA dissection among 236 patients with acute type A aortic dissection. These results are consistent with our findings. The higher incidence of RCA dissection is attributed to the fact that a false lumen most often develops in the right anterior aspect of the ascending aorta.

Previous studies have described patients who had acute type A aortic dissection with coronary artery dissection associated with myocardial ischaemia. In the present study, we included patients without myocardial ischaemia in the analysis and found that 64% of patients with coronary artery dissection had myocardial ischaemia.

After aortic repair, 7 patients had myocardial ischaemia with decreased left ventricular wall motion at the time of weaning from the heart–lung machine. Kawahito et al. [3] similarly reported that ischaemia developed on weaning from the heart–lung machine in 3 of 12 patients with coronary artery dissection accompanied by ischaemia. The development of ischaemia is most likely caused by pressure differences occurring between the true lumen and false lumen at the aortic root after repair, rather than the extension of dissection to the coronary arteries after aortic root repair. Residual minor leakage into the thrombosed false lumen at the aortic root may preclude a smooth decrease in false-lumen pressure during diastole, despite dilatation of the false lumen during systole, creating a pressure difference and compression of the true lumen. Therefore, the presence or absence of new ischaemic lesions and the development of decreased wall motion should be confirmed, and CABG or other procedures for coronary artery reconstruction should be additionally performed if necessary.

Our results showed that preoperative CPA was more common among patients with myocardial ischaemia than those without myocardial ischaemia. Because the presence of myocardial ischaemia, CPA and ischaemia in the territory of the LCA are risk factors for operative death and postoperative LOS, minimizing preoperative myocardial damage due to myocardial ischaemia may have an important role in decreasing operative mortality and maintaining good postoperative cardiac function. In particular, if the LCA is the culprit artery, the area at risk is extremely large, potentially leading to extensive myocardial damage.

Reimer and Jenning [5] experimentally compared the effects of reperfusion 40 min after proximal circumflex occlusion, reperfusion 3 h after proximal circumflex occlusion and permanent circumflex ligation in dogs. The rates of myocardial necrosis were 28, 70 and 72%, respectively, in the ischaemic bed at risk in infarcts. Even if reperfusion was performed 3 h after occlusion, most of the myocardium in the affected territory would thus have fallen into irreversible necrosis.

Francone et al. [6] used cardiovascular magnetic resonance to evaluate patients with ST-segment elevation myocardial infarction and found that the salvaged myocardium markedly decreased when the time to reperfusion by coronary intervention exceeded 90 min after coronary occlusion. Consequently, several bridge approaches to surgery have been developed to facilitate early coronary revascularization and reduce the extent of myocardial cell necrosis. Preoperative stent implantation and the placement of a coronary perfusion catheter have been reported to be effective in patients with coronary artery dissection [7–13]. However, evidence is limited to case reports, and the effectiveness of these procedures has yet to be demonstrated statistically. In the present study, preoperative coronary stent implantation was associated with a significantly lower risk of postoperative LOS, although the number of patients who received stent implantation for preoperative myocardial ischaemia was only 7.

One of the problems of coronary stent placement is an increased risk of subacute thrombosis in the absence of antiplatelet therapy after stent deployment. In particular, bleeding may persist after aortic surgery or early antiplatelet therapy cannot be started because of other haemorrhagic complications. Moreover, long-term antiplatelet therapy in patients with residual distal dissection can have negative effects on thrombosis of the false lumen. Given these potential problems, it might be best to additionally perform CABG of the same perfusion territory at operation, even if coronary revascularization is successfully achieved by coronary stent placement.

Another problem is that it can be difficult to accurately insert a guide-wire in the distal true lumen of the coronary artery and then place a stent in the true lumen in patients with circumferential detachment of the dissected intima in coronary ostial lesions. Fortunately, none of our patients had LCA dissection with intimal detachment, which is the most critical type of dissection. Catheterization procedures in the presence of aortic root dissection may carry the risk of exacerbating the dissection or damaging the intimal flap.

If coronary stenting is first performed in the catheterization laboratory, aortic repair is delayed and the risk of aortic rupture increases during this period. We, therefore, believe that coronary stenting should be performed in the presence of LCA dissection with ischaemia, which carries a very high risk of mortality from coronary artery ischaemia (49%). In patients with RCA dissection, associated with a smaller impact on myocardial blood flow and lower mortality, aortic repair should be performed initially, excluding patients in whom the initial diagnosis is made in the cardiac catheterization laboratory. However, the future use of hybrid operation rooms may reduce the risk of aortic rupture.

As for surgical procedures, Neri et al. [1] aggressively performed the Bentall operation to achieve coronary artery revascularization. The origin of the dissected coronary artery was partially resected, and patch repair was performed. The dissected coronary artery cuff was reinforced with a continuous suture, and the origin of the coronary artery was anastomosed to a synthetic ascending aortic graft. In patients with circumferential detachment of the dissected intima, good results have been obtained by reconstruction of the dissected coronary artery with a saphenous vein interposition graft. On the other hand, Kawahito et al. [3] obtained good results in most patients regardless of the type of coronary lesion by performing CABG with a saphenous vein graft, without directly touching the dissected coronary artery. This procedure carries the risk of late graft failure and occlusion of the proximal anastomosis with the vascular graft, but is simple and less invasive. It might be the best procedure for revascularization designed to save the patient's life during the acute phase.

Lentini and Perrotta [14] proposed that local repair is more straightforward than CABG in patients with coronary dissections that are limited to the coronary ostium. We basically close the false lumen at the aortic root, including the area around the coronary ostium, with biological glue and simultaneously perform CABG if necessary. The Bentall operation is performed only in patients who have entry or rupture sites in the aortic root. In patients who had RCA dissection with intimal detachment, the dissected coronary artery is resected and freed and then directly anastomosed to a side hole in a vascular graft.

Kazui [15] reported that the use of blood cardioplegia delivered both retrograde via the coronary sinus and antegrade through the non-dissected coronary ostium is useful for myocardial protection in patients with coronary artery dissection. In the present study, cardioplegia was delivered by both routes in 71% of the patients. Despite the fact that 21% of the patients with myocardial ischaemia had preoperative CPA, the operative mortality rate in this subgroup of patients was 33%, indicating relatively good results. This is attributed to the effectiveness of myocardial protection as well as early coronary revascularization by preoperative stent replacement.

Patients with myocardial ischaemia and coronary artery dissection have high mortality rates. Some of these patients have irreversible myocardial damage, making it difficult to maintain vital functions before surgery. Kazui [15] recommended the establishment of exclusion criteria for emergency operation in such patients. Patients with advanced myocardial damage who cannot recover from shock even after early preoperative coronary revascularization by stent placement should probably be excluded as candidates for surgical treatment. However, in younger patients who are free of serious noncardiac diseases, it may be possible to place a ventricular assist device after aortic repair, followed by the permanent implantation of an assist device. Heart transplantation may even be possible in a small percentage of patients.

Our study had several limitations. It was retrospective, and the results were probably affected by selection bias because surgery was contraindicated in patients unable to undergo cardiopulmonary resuscitation. Consequently, the overall survival rate of patients with coronary artery dissection, including patients who do not undergo surgery, may be even lower. Because our study group was small, it was not possible to perform multivariate analysis, and the results of univariate analysis are of limited value. Another limitation was that we did not evaluate the long-term outcomes of treatment.

CONCLUSIONS

Myocardial ischaemia associated with coronary artery dissection in patients with acute type A aortic dissection carries a high risk of extensive irreversible myocardial damage, potentially leading to preoperative cardiac arrest. These factors are considered mainly responsible for operative death and compromised diminished cardiac function after surgery. Early coronary revascularization should be performed to minimize the extent of myocardial cell necrosis and thereby reduce postoperative cardiac dysfunction.

Conflict of interest: none declared.

REFERENCES

APPENDIX. CONFERENCE DISCUSSION

Dr C. Etz(Leipzig, Germany): Your study deals with the timely topic of risk analysis and management of patients with acute type A aortic dissection and involvement of the coronaries. In your cohort, the percentage of patients coming in with coronary involvement is slightly higher than in other cohorts. About a decade ago, Neri and Spittell reported a 6% to 12% incidence. To me that means that you have a very efficient system in getting the patients to your hospital, because I would assume that many patients in other societies and other locations do not make it, actually, when they've got this involvement. Could you comment on this, just briefly.

I have two quick questions. You were describing the different lesions and the distribution in your cohort. Do you have follow-up data so that we can learn more about what the most dangerous involvement is, when do we have to be even quicker? Is there a certain subgroup that you should rush into the cath lab to get the stent implanted, or is there a group where we can say we do that in the OR? Sometimes it's very young patients, do we even have time maybe to do a mammary, so do an arterial revascularization, because most of the time they get pain. That's question number one.

Dr Imoto: It's a very tough question. We have a heart team with a cardiologist and surgeon, so we're usually discussing this kind of patient. If we have coronary dissection with the left coronary artery, we send the patient to the catheterization room because it causes very extensive myocardial damage. If the patient has a right coronary artery dissection, we do the operation. But if diagnosis was done in the catheterization room, we put the coronary stent first in that kind of patient.

Dr Etz: All right. And then another question, we were just about to analyse our data from Leipzig (it has a dissection group almost as large as yours), and what we saw is a different pattern in terms of root involvement between patients with bicuspid aortic valves and patients with tricuspid valves. And interestingly, the patients that had bicuspid valves more often have a root involvement, so the entry is more often in the root, than in tricuspid patients. However, these patients do not necessarily have an involvement of the coronaries more often. So it's about, I think, 3% versus 10%, if you look at bicuspids versus tricuspid patients. Did you look into that question in your cohort?

Dr Imoto: Maybe the frequency of the bicuspid valve is very much different between Asian and Western people. In this series we have no bicuspid valve patients.

Dr Etz: Zero in 500?

Dr Imoto: Zero in 75 patients with coronary artery dissection.

Dr E. Rosseykin(Penza, Russian Federation): I want to know if you have a problem with the right coronary artery. If you decide to place a vein graft to the right coronary artery, where do you place the distal anastomosis?

Dr Imoto: Of course, it depends on the extent of the dissection. But usually, in most of the cases, the dissection is limited to the proximal part of the right coronary artery. So we just put the anastomosis in segment 2 or 3.

Dr W. Morshuis(Nieuwegein, Netherlands): I would certainly have a problem with taking the patients to the angio and having a big time delay. Why don't you take the patients immediately to the operating theatre, make the time as short as possible, give cardioplegia and then do your repair? That's my first question.

And the second is I have a concern about the BioGlue you use in the coronary ostia to repair the lesion. It's known that it can cause inflammation, necrosis, even false aneurysms. So do you have follow-up on these patients? Do you have long-term follow-up? Is there concern about stenosis, for instance, in the coronary artery?

Dr Imoto: In terms of the risk of coronary dissection, the time is very important to save the myocardium. So even if we do the coronary revascularization during surgery, it takes more than 1 or 2 h for revascularization. So the stenting is faster. Usually our cardiologists do that within 30 min of the decision. That is why we do the stenting first for the patient with left coronary artery dissection.

Regarding the second question, we use GRF glue. But, as you know, there is a toxic effect of the formalin. We had pseudoaneurysms in almost 20% of the patients after repair using GRF glue. So we have stopped using it since 2006. Recently, we are using fibrin glue. Pseudoaneurysm has not occurred with the use of fibrin glue up until the present. It also has the satisfactory effect of adhesion around the dissected coronary artery.

Dr Morshuis: So it is a worry. My last question would be: if you stent the left coronary artery - you're in the operating theatre and you see that you actually stented a dissected vessel in which the dissection goes into the left coronary artery, would you take out the stent or just leave it because there is kind of an entry there? It's not a covered stent.

Dr Imoto: Cardiologists are doing that but, fortunately, we haven't had that kind of case so far.

Dr S. Leontyev(Leipzig, Germany): In my opinion, stent implantation for a patient with type A dissection is a challenge. My question is: did you have any technical problem with stent implantation, acute perforation of the aortic root or some other complication?

Dr Imoto: Yes. I showed one case we lost. The cause of death of that patient was subacute thrombosis of the stent. It occurred 17 days after operation. Before that the patient's condition was good, but the patient had intestinal bleeding. Then we stopped anticoagulant therapy. After that the subacute thrombosis occurred. So recently we add CABG in every case even after successful recanalization with stenting.

Dr T. Sioris(Tampere, Finland): Perhaps you already mentioned in your presentation, but just to make it clear for myself, two questions. First, do you do your angiographies in the operating room? Do you have a hybrid operating room where you can do it when the patient is undergoing the surgery in order to avoid time delays in taking to the cath lab? And my second question is: when exactly do your patients go for angiography? Because if you take them to the cath lab and you do the angio, you risk rupture of the dissected aorta and you risk, for sure, pressurization of the false lumen and all kinds of problems when the patients are sick. And I think what you are saying is very important, I just would like to be able to select my patients correctly for this kind of thing, which is not the usual routine in any publication.

Dr Imoto: Unfortunately, we don't have a hybrid operating room right now, but I think this kind of procedure should be done in a hybrid operating room. But we decide the strategy of the patient in the emergency room with the cardiologist. And as I said before, if the risk of the coronary ischaemia and the rupture are compared in the patient with left coronary artery dissection, we think the risk of the coronary dissection is higher than the rupture of the aorta. So that is our rationale for what we are doing.

Author notes