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Archives of cardiovascular diseases
Volume 110, n° 1
pages 14-25 (janvier 2017)
Doi : 10.1016/j.acvd.2016.05.007
Received : 30 January 2016 ;  accepted : 12 May 2016
Outcomes after surgery for acute type A aortic dissection in “non-Marfan syndrome” patients with long life expectancy: A 24-year follow-up
Résultats à très long terme après chirurgie pour dissection aortique aiguë de type A chez le patient avec une longue espérance de vie non atteint du syndrome de Marfan
 

Alessandro Piccardo a, , Tommaso Regesta b, Alexandre Le Guyader a, Nicola Di Lorenzo b, François Bertin a, Francis Pesteil a, Elisabeth Cornu a
a Service de chirurgie thoracique et cardiovasculaire, CHU Dupuytren, avenue Martin-Luther-King, 87000 Limoges, France 
b San Martino University Hospital, Genova, Italy 

Corresponding author.
Summary
Background

Long-term survival and risk of reoperation in “non-Marfan syndrome” patients with a long life expectancy who undergo emergency surgery for acute type A aortic dissection (aTAAD) are not well known.

Aim

To analyse survival, risk of reoperation and quality of life in this population.

Methods

From 1990 to 2010, all patients aged50 years and not affected by Marfan syndrome, who underwent emergency surgery for aTAAD at two institutions, were included in this analysis. Patients were categorized into four groups according to the extension of the aortic replacement: SUPRACORONARY, ROOT, ARCH and EXTENSIVE.

Results

Sixty-six patients (mean age 45±4 years; range 34–50 years) were considered eligible for this analysis. Overall in-hospital mortality was 24% (16/66 patients); and 25%, 23%, 20.5% and 43% in the SUPRACORONARY, ROOT, ARCH and EXTENSIVE groups, respectively. Mean follow-up among survivors was 10.5±7.2 years (range: 0.1–24.7 years). Overall 10-year survival was 55±6%; and 75±12%, 69±13%, 47±8% and 28±17% in the SUPRACORONARY, ROOT, ARCH and EXTENSIVE groups, respectively. Overall freedom from reoperation on the aorta was 73±7.5%; and 40±20%, 75±21%, 78±8% and 100% in the SUPRACORONARY, ROOT, ARCH and EXTENSIVE groups, respectively.

Conclusions

In our experience, patients who underwent isolated supracoronary ascending aorta or root replacement showed the most satisfactory late survival. However, because the risk of reoperation is low when the replacement is extended to the root, our data suggest that root replacement could represent a good compromise between operative mortality and long-term survival.

The full text of this article is available in PDF format.
Résumé
Contexte

Les résultats à très long terme après chirurgie pour dissection aortique aiguë de type A chez le patient avec une longue espérance de vie non atteint du syndrome de Marfan sont peu connus.

Objectifs

Nous analysons la survie et le risque de réintervention dans cette population.

Méthodes

Nous avons analysé rétrospectivement tous les patients âgés de moins de 50ans, non atteints du syndrome de Marfan et opérés d’une dissection aortique aiguë de type A dans deux hôpitaux, entre 1990 et 2010. Les patients ont été repartis en 4 groupes selon l’extension du remplacement aortique : SUS-CORONAIRE, RACINE (étendu que à la racine), ARCHE (étendu que à l’arche) et ETENDU (de la racine à l’arche).

Résultats

Soixante-six patients (âge moyen : 45±4ans; de 34 à 50ans) ont été inclus dans cette analyse. La mortalité hospitalière globale était de 24 % (16/66 patients) et de 25 %, 23 %, 20,5 % et 43 % dans les groupes SUS-CORONAIRE, RACINE, ARCHE et ETENDU, respectivement. Le suivi moyen parmi les survivants était de 10,5±7,2ans (de 0,1 à 24,7 ans). La survie à 10ans (mortalité hospitalière incluse) était de 55±6 %, 75±12 %, 69±13 %, 47±8 % et 28±17 %, dans les groupes SUS-CORONAIRE, RACINE, ARCHE et ETENDU, respectivement. La liberté d’une réintervention sur l’aorte à 10ans était de 73±7,5 %, 40±20 %, 75±21 %, 78±8 %, dans les groupes SUS-CORONAIRE, RACINE, ARCHE et ETENDU, respectivement.

Conclusion

Dans notre série, les patients qui ont bénéficié d’un remplacement de l’aorte sus-coronaire ou d’un remplacement de la racine aortique présentent la meilleure survie au long terme. Toutefois, puisque le risque de réintervention est faible après remplacement de la racine aortique, nos données suggèrent que le remplacement de la racine aortique semble être un bon compromis entre la mortalité hospitalière et la survie au long terme.

The full text of this article is available in PDF format.

Keywords : Aortic dissection, Surgery, Survival, Young

Mots clés : Dissection aortique, Chirurgie, Survie, Jeune

Abbreviation : aTAAD


Background

Long-term outcomes after surgery for acute type A aortic dissection (aTAAD) in patients with a long life expectancy are unclear. While survival after surgical repair has been thoroughly investigated, studies reporting long-term follow-up in the young (mean follow-up>5 years) are anecdotal, and included a variable proportion of patients affected by Marfan syndrome [1, 2, 3, 4, 5, 6, 7, 8, 9].

Management of aTAAD in Marfan syndrome patients is unanimous. Extensive aortic replacement has been suggested to improve survival and minimize the risk of reoperation at late follow-up. However, survival of non-Marfan syndrome patients with a long life expectancy has not been analysed extensively. For these patients, it is still unclear whether a more extensive aortic replacement is justified to improve overall survival.

We reviewed our 20-year experience in the management of aTAAD, with the aim of analysing the impact of surgical aggressiveness on very-long-term survival and risk of reoperation in non-Marfan syndrome patients with a long life expectancy.

Methods

From January 1990 to December 2010, 554 patients underwent emergency surgery for aTAAD at the “Dupuytren” University Hospital (Limoges, France) and at the “San Martino” University Hospital (Genova, Italy). All patients aged50 years were screened initially; among these, patients affected by Marfan syndrome were excluded. The diagnosis of Marfan syndrome was based on clinical criteria (the Ghent nosology). None of the patients underwent DNA testing at our institution for FBN1 mutation.

The Institutional Ethics Committee approved the study protocol, and authorized its conduction and follow-up. Individual patient consent was obtained for the study.

Data collection

Data on patient demographics, medical and surgical treatment details and in-hospital patient outcomes were collected by physicians, and were obtained by review of hospital records (Appendix 1). Yearly follow-up data were obtained by clinical examination or by telephone interview. No patient was lost at the last follow-up (01 January 2015). Data were forwarded to the coordinating physician (A.P.); forms were then reviewed and validated before statistical analysis.

Data analysis

Data analysis was performed using the JMP statistical analysis software (SAS Institute, Cary, NC, USA). Continuous variables are presented as means±standard deviations and categorical variables are expressed as frequencies.

For the purpose of this analysis, we categorized patients into four groups, according to the extension of the aortic replacement. The SUPRACORONARY group included all patients who underwent isolated supracoronary ascending aorta replacement; in these patients the distal anastomosis was realized without removing the aortic clamp. The ROOT group included all patients in whom the replacement supracoronary ascending aorta was extended to the root; in these patients the distal anastomosis was realized without removing the aortic clamp. The ARCH group included all patients in whom the replacement of the supracoronary ascending aorta was extended to the concavity of the arch or to the proximal hemiarch or to the whole aortic arch. The EXTENSIVE group included all patients who underwent replacement of the aorta from the root to the concavity of the arch or to the proximal hemiarch or to the whole aortic arch.

Continuous variables were compared using Student's t -test or the Wilcoxon rank-sum test. Categorical variables were compared using the χ2 test or Fisher's exact test (two-tailed test) if the expected count in any cell was<5.

For the multivariable analysis, all variables that reached a P value ≤0.2 in the univariate analysis were then included in a stepwise logistic regression, provided they were present in ≥2% of the samples. Retention of risk variables was determined by using the likelihood ratio test. We considered a P value<0.05 to be significant.

Survival was determined by the Kaplan–Meier method, and is expressed as the proportion±standard error.

Results
Study population

During the study period, 654 patients underwent surgery for aTAAD at the participating centres; among these, 79 (12%) were aged50 years, and 66 patients (10%) were considered eligible for this analysis. Table 1 details demographics, history and clinical presentation for our patient population.

The mean age was 45±4 years (range 34–50 years); 12 patients (18%) were young. The majority of patients had a history of hypertension, and a third of patients were active smokers. Four patients (6%) had a history of previous cardiac surgery (aortic valve replacement in two patients, mitral valve replacement in one patient and atrial septal defect closure in one patient), at least 3 years before the acute aortic dissection.

Twelve patients (18%) presented a complicated dissection because of a preoperative neurological deficit and/or haemodynamic compromise.

Table 2 details demographics, history and clinical presentation according to the extension of the aortic replacement. The distribution of age was similar among the groups (P =0.57). However, patients in the SUPRACORONARY group were younger because a third were aged<40 years. Patients in the SUPRACORONARY and EXTENSIVE groups had no history of previous cardiac surgery. Patients in the ROOT and EXTENSIVE groups had no neurological deficit before the surgery.

Surgical procedure

Surgical procedures are detailed in Table 1. All patients underwent surgery within 48hours after the onset of symptoms. In all patients, the diagnosis of ascending aortic dissection was confirmed at operation. Surgical management varied among the participating centres, but all patients underwent a tear-oriented approach to find and resect the proximal intimal tear. Site of arterial cannulation was femoral in most patients. Cardioplegic arrest was achieved by selective crystalloid cardioplegia repeated every 40minutes. Two patients underwent arch cannulation, as previously described [10]. The replacement technique always included the interposition of a Dacron tube with a Teflon® felt strip (DuPont, Wilmington, DE, USA), and reinforcement of the aortic stump with gelatin-resorcinol-formaldehyde or biological glue.

The majority of patients (41/66 patients) underwent circulatory arrest to replace the aortic arch (partially or totally). Circulatory arrest was performed in deep (17°C) or moderate (25°C) hypothermia. All patients operated on in the early period (1990–2000) underwent deep hypothermic circulatory arrest: the head was placed in a tub for additional topical brain protection with ice, and no antegrade or retrograde cerebral perfusion was performed. From 2000, arch surgery was performed with deep or moderate hypothermic circulatory arrest. In all these patients, brain protection was achieved by unilateral cerebral protection, involving perfusion of the right axillary artery (10mL/kg/min and left radial artery pressure50mmHg) or selective bilateral carotid perfusion. Bilateral carotid perfusion was performed in all patients undergoing femoral or aortic cannulation, or when the surgeon detected signs of incomplete circle of Willis (left radial arterial pressure<50mmHg).

Almost 40% of patients (25/66 patients) underwent surgical repair without circulatory arrest. The distal anastomosis was performed without removing the aortic clamp. Among these, half of the patients underwent isolated supracoronary ascending aorta replacement (the SUPRACORONARY group; n =12), and half of patients underwent root replacement (the ROOT group; n =13). In all patients, root replacement was realized by a composite mechanical valved conduit.

Five patients (7.5%) presented severe right ventricular dysfunction during the weaning of the cardiopulmonary bypass, and the surgeon decided to perform a coronary artery bypass graft to the right coronary artery. Six patients (9%) presented preoperative “moderate-to-severe” aortic valve regurgitation without presenting a root dilation; they underwent replacement of the aortic valve with a mechanical prosthesis.

Table 2 details operative procedure according to group. As expected, the cardiopulmonary bypass time was longer in the ARCH and EXTENSIVE groups. No patient in the SUPRACORONARY or ROOT groups underwent axillary artery cannulation for the establishment of cardiopulmonary bypass.

Early outcomes

In-hospital mortality was 24% (16/66 patients). The primary causes of death were cardiac failure (n =9), multiorgan failure (n =2), neurological damage (n =2), haemorrhagic shock (n =2) and refractory cardiac arrest (n =1). In three patients, cardiac failure was related to the dissection of the right coronary ostium; they first underwent “not planned” coronary artery bypass grafting, and then extracorporeal membrane oxygenation implantation because of refractory left ventricular dysfunction. All patients on extracorporeal life support died because of multiorgan failure (n =2) or sepsis (n =1). In the remaining six patients, cardiac failure was associated with a long cross-clamping time because of extensive and complex aortic replacement (required to accomplish the aortic replacement). In two patients, multiorgan failure occurred despite preserved cardiac function, and was more likely related to the “malperfusion syndrome”. Intraoperatively, haemorrhagic shock despite optimal coagulation therapy occurred at root level in patients who underwent root replacement and supracoronary replacement. Among five patients presenting preoperative neurological deficit, one patient presented a preoperative coma and died, and four patients were discharged; two of these patients did not recover.

Table 3 details the univariate analysis for in-hospital mortality. Mortality was higher in patients presenting with preoperative neurological deficit (60% vs. 21.3%; P =0.08). Even if the impact of surgical aggressiveness on early mortality did not reach statistical significance, patients who died during the hospitalization presented a longer cardiopulmonary bypass time, which is usually required during arch or root replacement (P =0.0021). The stepwise logistic regression identified “age” (P =0.0471) and “cardiopulmonary bypass time” (P =0.0046) as independent risk factors for in-hospital mortality.

Half of the patients experienced a postoperative complication (Table 1). The rate of postoperative complications was similar regardless of surgical aggressiveness (P =0.54) (Table 2).

Early outcomes according to the extension of the aortic replacement
Early outcomes in the SUPRACORONARY group

In-hospital mortality was 25% (3/12 patients). Among these, two patients died because of cardiac failure, and one died because of refractory cardiac arrest in the intensive care unit. Five patients (41.5%) developed a postoperative complication.

Early outcomes in the ROOT group

In-hospital mortality was 23% (3/13 patients). Among these, two patients died because of cardiac failure, and one died because of haemorrhagic shock. Seven patients (54%) developed a postoperative complication.

Early outcomes in the ARCH group

In-hospital mortality was 20.5% (7/34 patients). Among these, four patients died of cardiac failure, two died of multiorgan failure, and one died of haemorrhagic shock. Fifteen patients (44%) developed a postoperative complication.

Early outcomes in the EXTENSIVE group

In-hospital mortality was 43% (3/7 patients). Two patients died of severe neurological damage, and one died because of cardiac failure. Five patients (71.5%) developed a postoperative complication.

Survival

The mean follow-up was 7.9±7.1 years (range: 0–24.7 years; 100% complete) or 10.5±7.2 years (range: 0.1–24.7 years; 100% complete) among the 50 discharged patients. Sixteen patients (32%; 16/50 patients) died during the follow-up, after a mean follow-up time of 4.8±4.5 years (median: 3.0 years). In the univariate analysis, the impact of surgical aggressiveness on late mortality did not reach statistical significance. The arch cannulation was the only variable to reach statistical significance (P =0.0295) (Table 4). Overall survival was 71±0.5%, 60±6%, 55±6%, 45±7% and 45±7% at 1, 5, 10, 15 and 20 years, respectively (Figure 1). Figure 2 details overall survival according to the extension of the aortic replacement. The impact of surgical aggressiveness on survival did not reach statistical significance (log-rank P =0.19; Wilcoxon P =0.23).



Figure 1


Figure 1. 

Overall survival among non-Marfan patients operated on for acute type A aortic dissection. pts: patients.

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Figure 2


Figure 2. 

Overall survival among non-Marfan patients operated on for acute type A aortic dissection, according to the extension of the aortic replacement. Red line: SUPRACORONARY group; green line: ROOT group; blue line: ARCH group; orange line: EXTENSIVE group. yr: year.

Zoom

Survival according to the extension of the aortic replacement
Survival in the SUPRACORONARY group

One patient (11%; 1/9 discharged patients) died after 14.7 years. Overall survival was 75±12%, 75±12% and 75±12% at 1, 5 and 10 years, respectively. Survival among discharged patients was 100% at 1, 5 and 10 years.

Survival in the ROOT group

One patient (10%; 1/10 discharged patients) died 2.7 years after the operation. Overall survival was 77±11%, 69±13% and 69±13% at 1, 5 and 10 years, respectively. Survival among discharged patients was 100%, 90±9% and 90±9% at 1, 5 and 10 years, respectively.

Survival in the ARCH group

Twelve patients (44%; 12/27 discharged patients) died after a mean time of 4.9±4.2 years. Overall survival was 73±7%, 58±8% and 47±8% at 1, 5 and 10 years, respectively. Survival among discharged patients was 92±5%, 73±8% and 60±10% at 1, 5 and 10 years, respectively.

Survival in the EXTENSIVE group

Two patients (50%, 2/4 discharged patients) died during follow-up. Overall survival was 42±17%, 28±17% and 28±17% at 1, 5 and 10 years, respectively. Survival among discharged patients was 50% at 1, 5 and 10 years.

Reoperation on the aorta

All discharged patients were included in a follow-up programme, based on annual transthoracic echocardiography and aortic computed tomography angiography, to assess the evolution of the proximal and distal aorta. During the follow-up, 12 patients (24%; 12/50 patients) underwent reoperation on the aorta after a mean time of 5.1±4.7 years (median: 3.8 years). Reoperations were equally distributed on the proximal and distal aorta, and in all patients the indication for reoperation was aneurysmal evolution of the dissected preserved aorta.

Six patients (12%; 6/50 patients) underwent reoperation on the proximal aorta and root replacement by the Bentall procedure: 5/50 patients (10%) on the distal aorta (one arch replacement; one arch and thoracic descending aorta with the E-vita endoprosthesis [JOTEC GmbH, Hechingen, Germany]; one conventional arch and thoracic descending aorta replacement; one isolated thoracic descending aorta replacement; and one thoracoabdominal aorta replacement) and 1/50 patients (2%) on the proximal and distal aorta.

Two of 12 patients (16%) died at the reoperation; they underwent replacement of arch and descending thoracic aorta, and replacement of the thoracoabdominal aorta.

In the univariate analysis, the impact of surgical aggressiveness on reoperation did not reach statistical significance (Table 5). However, patients who did not undergo reoperation presented longer cardiopulmonary bypass and cross-clamping times (which are usually required during arch or root replacement), even if these did not reach statistical significance. The impact of surgical aggressiveness on late reoperation did not reach statistical significance (log-rank P =0.23; Wilcoxon P =0.16). Overall freedom from reoperation on the aorta was 96±2.5%, 81±6%, 73±7.5%, 58±11% and 58±11% at 1, 5, 10 and 20 years, respectively (Figure 3). Figure 4 details freedom from reoperation according to the extension of the aortic replacement.



Figure 3


Figure 3. 

Overall freedom from reoperation among non-Marfan patients operated on for acute type A aortic dissection. pts: patients.

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Figure 4


Figure 4. 

Overall freedom from reoperation among non-Marfan patients operated on for acute type A aortic dissection, according to the extension of the aortic replacement. Red line: SUPRACORONARY group; green line: ROOT group; blue line: ARCH group; orange line: EXTENSIVE group. yr: year.

Zoom

Freedom from reoperation according to the extension of the aortic replacement
Freedom from reoperation in the SUPRACORONARY group

Four patients (44%; 4/9 discharged patients) underwent reoperation after mean time of 3.3±2.4 years. All patients experienced an aneurismal evolution of the root, and underwent root replacement. In one patient, the root aneurysm was associated with arch enlargement, and he underwent root and arch replacement. Overall freedom from reoperation was 89±10%, 61±18% and 40±20% at 1, 5 and 10 years, respectively.

Freedom from reoperation in the ROOT group

One patient (10%; 1/10 discharged patients) presented an aneurismal evolution of the arch, and required reoperation 9.3 years after surgery; he died at the reoperation. Overall freedom from reoperation was 100%, 100% and 75±21% at 1, 5 and 10 years, respectively.

Freedom from reoperation in the ARCH group

Seven patients (26%; 7/27 discharged patients) underwent reoperation after a mean time of 5.5±5 years. Six patients underwent replacement of the distal aorta. One patient underwent root replacement. One patient died at the reoperation; he underwent replacement of the thoracoabdominal aorta. Overall freedom from reoperation was 96±3%, 78±8% and 78±8% at 1, 5 and 10 years, respectively.

Freedom from reoperation in the EXTENSIVE group

No patient underwent reoperation during the follow-up. Overall freedom from reoperation was 100% at 1, 5 and 10 years.

Autonomy and quality of life

Autonomy and quality of life were not precisely quantified according to a validated scale. However, almost all discharged patients (48/50 patients; 96%) were completely autonomous, and were able to return to normal activities. Among the four discharged patients who experienced postoperative stroke, two patients did not recover, and the permanent neurological deficit impaired their degree of autonomy.

Discussion

The objective of surgical repair for aTAAD is to reverse the dismal prognosis of this pathology. Because of the potential natural evolution of the remaining aorta during follow-up, to reverse the prognosis means not only to improve early survival, but also to prevent rupture of the remaining aorta at late follow-up.

The risk of adverse outcome during the follow-up period is especially evident in patients with a long life expectancy. In such patients, the optimal extension of the aortic replacement to reduce mortality and late complication is still a matter of debate.

Longitudinal analyses in the young are based on a short mean follow-up, and are biased by the inclusion of patients with Marfan syndrome. While survival in Marfan patients is deeply affected by the Marfan disease, less is known about long-term outcomes in young patients operated on for aTAAD and not affected by Marfan syndrome.

To our knowledge, this analysis is the largest and longest study on young adults undergoing surgery for aTAAD. We believe that some observations can be made. First, overall survival after surgical repair is satisfactory. During a mean follow-up of 10 years, more than half of the patients were still alive 10 years after surgery. Moreover, even if we did not quantify their degree of autonomy and quality of life, almost all discharged patients (96%) were completely autonomous and were able to return to normal activities. The analysis of survival according to the extension of the aortic replacement is interesting. In our experience, as the extension of the aortic replacement increases, overall survival decreases. While patients who underwent isolated supracoronary replacement or root replacement had an excellent survival rate (70–75% at 10 years), fewer than half of the patients (30–50%) who underwent arch replacement or extensive replacement were still alive 10 years after the operation. Because of similar in-hospital mortality among the groups, the survival gap seems primarily related to the late mortality. Indeed, if we considered only discharged patients, survival at 10 years was from 30–60% in the ARCH and EXTENSIVE groups versus 90–100% in the SUPRACORONARY and ROOT groups.

As expected, the overall risk of reoperation rate at follow-up was not marginal, but good, considering the potential natural evolution of the remaining aorta. Freedom from reoperation on the aorta was 73% at 10 years after the operation. In our experience, the risk of reoperation is equally distributed between the proximal and distal aorta (six reoperations on the proximal aorta and six reoperations on the distal aorta). The subgroup analysis gives reason for reflection. Patients in whom the root and the arch were both preserved had the highest risk of reoperation rate (40% of patients were free from reoperation 10 years after the operation). In these patients, the risk of aneurismal evolution was essentially related to the proximal aorta. By comparison, patients who underwent root replacement had a low risk of reoperation. However, even if these findings support a more aggressive approach at the root level, root replacement was not associated with a survival benefit compared with patients who underwent isolated supracoronary replacement. More interesting, patients who underwent arch replacement were still at risk of aneurismal evolution at the distal aorta, as almost all patients in the ARCH group were reoperated on the distal aorta. This is because the majority of patients in the ARCH group underwent replacement of the proximal part of the arch at first operation. Our experience suggests that resection of the proximal part of the aorta does not protect from the aneurismal evolution of the distal aorta.

Conclusion

In our experience, patients who underwent isolated supracoronary ascending aorta or root replacement had the most satisfactory late survival. However, because the risk of reoperation is low when the replacement is extended to the root, our data suggest that root replacement could represent a good compromise between operative mortality and long-term survival.

Disclosure of interest

The authors declare that they have no competing interest.


Appendix 1. Covariates assessed

Demographic and history covariates

Age, sex, obesity, coronary artery disease, hypertension, diabetes mellitus, active smoking, chronic obstructive pulmonary disease, previous cardiac surgery, bicuspid aortic valve and Marfan syndrome.

Preoperative clinical covariates

Cardiac effusion, cardiac tamponade, shock, stroke, coma, paraplegia, visceral ischaemia, acute renal failure and cardiopulmonary resuscitation.

Anatomical and operative covariates

Site of arterial cannulation, site of intimal tear, resection of the proximal intimal tear, intraoperative aortic rupture, aortic cross-clamping (categorical covariate), cross-clamping time, cardiopulmonary bypass time, circulatory arrest, cerebral perfusion during circulatory arrest, core temperature at circulatory arrest, extension of aortic replacement and associated procedures.

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