International Journal of Cardiology 184 (2015) 285–290
Contents lists available at ScienceDirect
International Journal of Cardiology
j ourna l homepage: www.e lsev ie r .com/ locate / i j ca rd
Aortic root surgery improves long-term survival after acute type Aaortic dissection☆
Ilir Hysi a, Francis Juthier a, Olivier Fabre b, Olivier Fouquet c, Natacha Rousse a, Carlo Banfi a, Claire Pinçon d,Alain Prat a, André Vincentelli a,⁎a Centre Hospitalier Régional et Universitaire de Lille, Lille 59035, Department of Cardiovascular Surgery, Franceb Centre Hospitalier de Lens et Hôpital privé de Bois Bernard, Lens, Department of Cardiac surgery, Francec Centre Hospitalier Universitaire d'Angers, Angers 42000, Department of Cardiovascular and Thoracic surgery, Franced Université Lille Nord de France, Lille 59000, UDSL, EA2694, Department of Biostatistics, France
☆ “All authors take responsibility for all aspects of the reof the data presented and their discussed interpretation”.⁎ Corresponding author at: Service de Chirurgie cardiaq
Objective: Our objective was to analyze the long term survival of patient operated on for acute type A aorticdissection.Methods: Between 1990 and 2010, 226 patients underwent emergency surgical operation for acute type A aorticdissection. We have followed the long-term outcomes.Results: 144 patients were operated on with a supracommissural replacement of the ascending aorta (SCR) and82with an aortic root surgery (ARS, including 77 Bentall procedures and 5 TironeDavid operations). Aortic cross-clampwas longer in ARS group (150.8 vs. 103.6 min, p b 0.0001). Overall in-hospital mortality was lower in ARSgroup (20% vs. 34%, p 0.03). Median follow-up was 11.6 years. 10-year survival was higher in ARS group (85.7%vs. 65.9%, p 0.03) and 10-year freedom from aortic root reoperation was significantly lower in ARS group (93.4%
vs. 82.9%, p 0.02). In amultivariate analysis aortic root surgerywas an independent protective factor for proximalreoperations OR 0.393, CI 95% [0.206–0.748], p = 0.005.Conclusions:Our study suggests that complete aortic root replacement in type A aortic dissection does not burdenshort-term outcomes, improves long-term survivals and decreases the rate of late reoperation.Whether this ap-proach has to be preferred in younger patient has to be demonstrated in further studies.
Surgical management of acute type A aortic dissection remains chal-lenging. Perioperative results have been widely reported yet there is nofull consensus in the literature regarding the choice of proximal repairsurgical technique and it still may remain a decision made on surgeon'sdiscretion or center's tradition. On one hand, the supracommissural re-placement allows the preservation of the native aortic valve without ananticoagulant treatment, but on the other hand, the complete root re-placement, a more demanding operation, may reduce later high riskproximal reoperations [1–3].Whether a long term resultmight be influ-enced by perioperative proximal management has not yet beendemonstrated.
Aims of the present study were to evaluate early and late outcomesof a consecutive cohort of patient operated on in our center on an
liability and freedom from bias
ue, Hôpital Cardiologique, CHRU
lli).
.
emergency basis for an acute type A dissection. The primary endpointwas to determine whether perioperative proximal surgical strategyhad improved late survival. The second endpoint was to evaluate thelatemortality and the reoperations' rate. A composite endpoint so calledevent-free survival was made with the probability to be free from latedeath and proximal reoperation.
2. Patients and methods
2.1. Population
This was a retrospective study of 226 consecutive patients operatedon, in an emergency basis, for acute type A aortic dissection betweenJanuary 1990 and December 2010. The whole cohort of patients had amean age of 59.2 (±19.9) years and there was mostly male (66%). Pa-tientswere operated according two surgical strategies: supracommissuralreplacement (SCR n = 144 patients); or aortic root surgery with orwithout aortic valve replacement (ARS n = 82 patients, 77 Bentall and5 Tirone David). The strategy regarding the surgical techniques wasguided by perioperative findings and surgeon's habitudes. Preoperativedata of the patients are summarized in Table 1.
286 I. Hysi et al. / International Journal of Cardiology 184 (2015) 285–290
The study was approved by the Institutional Review Board ofthe French Society of Thoracic and Cardio-Vascular Surgery (CERC-SFCTCV-2013-7-29-17-7-0-HyIl).
2.2. Surgical techniques
According to surgeon's preferences, cardiopulmonary bypass (CPB)was established between the femoral or axillary artery and the rightatrium or both vena cava. Since 1999 [4], the antegrade axillary arterialperfusionwasmore andmore performed. TheARS group beingmore re-cent in our cohort, the antegrade axillary arterial perfusion was morefrequent than the retrograde femoral arterial perfusion, in the lattergroup. Myocardial protection was achieved by antegrade and/or retro-grade cold blood cardioplegia repeated every 30 min with a warmblood reperfusion. In case of ascending aorta replacement, the aorticwall was felt with surgical glue (Bioglue, Cryolife, Kennesaw, GA) andthe aortic valve was resuspended in case of aortic regurgitation. Aorticroot replacement was performed with a usual Bentall procedure. Bio-logical Bentall was made with a pericardial valve sutured to a Dacronprosthesis and then anchored to the left ventricle orifice. In somecases a valve sparing procedure was performed according to the inclu-sion techniquewith aGelweaveValsalva prosthesis (GelweaveValsalva,Vascutek, Inchinnan, UK). In both groups distal open anastomosis wasperformed most of the time during a circulatory arrest with anantegrade cerebral perfusion at 28 °C.
2.3. Postoperative management
After the surgical procedure, patients were monitored at the inten-sive care unit (ICU) for at least 48 h. In case of early visceralmalfunction(kidney, liver) a CT scan was emergently performed to rule out any pe-ripheral malperfusion syndrome. Before discharge, all patients had athoraco-abdominal contrast-enhanced CT Scan, which served for theinitial assessment of the distal aortic lesions. Furthermore, a 24-hourblood pressure Holter monitor was performed to guide the long-termantihypertensive treatment.
2.4. Follow-up
All patients who survived the operation were followed up. Eventswere defined as death or aortic root reoperation. All patients had a reg-ular cardiac follow-up during the first year after surgery with CT scan at6 months and/or 1 year. Operative mortality included all patients whodied within 30 days of surgery and patients never leaving the hospital.Recent clinical data were collected by telephone interviews, from thepatients or their attending physicians or cardiologists. Survival was
defined as the time lapsed from the date of surgery until the date ofdeath or the endof the follow-up termination time (right censoring) ex-cluding postoperative mortality.
2.5. Statistical analysis
Analyses were conducted using SAS software (SAS version 9.1, SASInstitute Inc., Cary, NC, USA). Continuous variables are expressed asmean+/− SD, and categorical variables are presented as absolute num-bers and percentages. Characteristics of subjects according to the type ofsurgical operation for acute type A aortic dissection were comparedwith Chi-square or Fisher's exact tests as appropriate for categorical var-iables and with Mann–Whitney U test for continuous variables.
Event-free survival curves were estimated using the Kaplan–Meiermethod and compared using the log-rank test. Median follow-up timewas estimated with the reverse Kaplan–Meier method. Univariatefollowed by multivariate Cox analyses were performed to assess theprognostic value of the type of surgical operation for acute type A aorticdissection on postoperative survival, proximal reintervention free sur-vival and freedom from proximal reintervention, first unadjusted thenadjusted on potential confounding factors. The log-linearity assumptionfor continuous variables and the proportional hazard assumption weretested by Kolmogorov-type supremum tests as implemented in thePROC PHREG of the SAS software (SAS version 9.1, SAS Institute Inc.,
Table 4Univariate and multivariate Cox analysis of factors affecting in-hospital mortality.
Postoperative myocardial infarction 11.375 [4.808–26.912] b0.0001Renal failure after 3 days of follow-up 5.200 [2.509–10.776] b0.0001SCR 2.257 [1.165–4.373] 0.02Age (per year) 1.042 [1.019–1.065] 0.0004CPB time (per min) 1.006 [1.001–1.010] 0.01
287I. Hysi et al. / International Journal of Cardiology 184 (2015) 285–290
Cary, NC, USA). In case of violation of the former assumption, the contin-uous variable was dichotomized, the cut-off value being visuallyestablished; in case of violation of the latter assumption, a piecewisemodel was used to model the hazard ratio as a step function of time,the cut-off value being again visually established. In both cases, it wasensured that the Schwarz's Bayesian Criterion was minimal. A two-tailed type I error rate b0.05 was considered for statistical significance.
3. Results
Table 1 resumes preoperative characteristics among the two groups.The proximal intimal tear of the aortic dissection was more frequentlyfound in the ascending aorta in the ARS group (93% vs. 80%, p 0.006).Also, in the ARS group, coronary bypasses at the end of the CPB were
Fig. 1. A: Kaplan–Meier survival; B
more frequent (9% vs. 1%, p = 0.007). This was related to the dissectingprocess in all cases (dissection of the coronary ostiumor artery). Table 2illustrates the perioperative data between the groups.
Overall in-hospitalmortality in the cohortwas 29% (67 patients) andit was higher in the SCR group. The specific causes of mortality were notdifferent between the groups (Table 3). In a univariate analysis(Table 4), overall in-hospital mortality was significantly influenced bya series of factors such as SCR, age, cardiogenic shock and peripheralmalperfusion. In multivariate analysis (Table 4) SCR, age, renal failurepersistent after 3 days of follow-up and myocardial infarction were sig-nificant independent factors for early mortality.
For the whole cohort, the mean duration of ICU and total hospitalstay were 6.9 (±11.1) days and 15.8 (±13) days, respectively. Opera-tive morbidity between the two groups was also comparable with re-gard to renal failure, myocardial infarction, prolonged mechanicalventilation, stroke, peripheral malperfusion and early reoperations(Table 3).
3.1. Survival
Mean follow-up was 9.1 (±0.5) years and median follow-up was11.6 years (range 0 to 22.7 years). 5-, 10- and 15-year survivals were87%, 72.5% and 69%, respectively (Fig. 1A). In the SCR group these sur-vival rates were 83.8%, 65.9% and 62.6%, while in the ARS group theywere 91.8%, 85.7% and 81.8%. Survival was higher in ARS group (log-rank p = 0.03, Fig. 1B).
3.2. Aortic root reoperations
During the follow-up of the 159 patients surviving the initial sur-gery, 17 surgical reoperations were required on the aortic root orvalve. Fifteen reoperations were performed in the SCR group: recurrentdissection of the aortic root (n= 7), progressive dilatation of the aorticroot with valve insufficiency (n = 7) and stenosis of the left main re-quiring bypass surgery (n = 1). In the ARS group two reoperationswere performed: one for aortic insufficiencywith commissural prolapseafter a Tirone David and one for bioprosthesis degeneration in a biolog-ical Bentall. The operativemortality of these reoperationswas 23% (n=4). All four deathswere observed in the SCR group. Themedian duration
: Survival among the groups.
Table 5Multivariate Cox analysis of factors affecting event-free survival.
288 I. Hysi et al. / International Journal of Cardiology 184 (2015) 285–290
between the index operation and the reoperation was 53.3 months(7.7–192.5 months).
3.3. Event-free survival (late death and proximal aorta reoperations)
For the entire cohort, 5-, 10- and 15-year event-free survivals were82.3%, 65.1% and 59.4%, respectively. In the SCR group event-free surviv-al rates were 76.1%, 57.2% and 51.0%, while in the ARS group they were91.8%, 79.6% and 75.6% (log-rank p = 0.008, Fig. 2A).
In a multivariate analysis, aortic root surgery (Bentall or TironeDavid) significantly improved event-free survival (Table 5).
3.4. Freedom from aortic root reoperation
For the entire cohort, the 5-, 10- and 15-year freedom values fromproximal reoperation were 92.9%, 87.1% and 83.7%, respectively. In theSCR group these rates were 88.2%, 82.9% and 78%, while in the ARSgroup they were 100%, 93.4% and 93.4% (log-rank p = 0.02, Fig. 2B).
4. Comment
Simon Kupilik et al. [5] showed in vitro and in vivo that thesupracommissural replacement of the aorta by a vascular prosthesis in-duced significant hemodynamic changes at the level of the aortic rootby increasing parietal tension as a result of the rigidity of the adjacentvascular prosthesis. Ergin et al. [6] first proposed the complete replace-ment of the aortic root for acute type A aortic dissection as a surgicaltechnique potentially reducing long-term reoperations. We havesummarized in Table 6 the rate of proximal aorta reoperation as it wasrecently published. The rate of reoperation in the ARS groups wasalways b10%. Only two studies have reported a mean follow-up ofmore than 9 years, one of these from Niclaus et al. [7] reported a rateof 23% of reoperation in the SCR group in selected young patients
Fig. 2. A: Event-free survival among the groups; B: Free
(b40 years). In our study, with amedian follow up of 11.6 years, we dem-onstrated that ARS with a Bentall or Tirone David procedure did notburdened perioperative results and was an independent significant pro-tective factor of survival and freedom from late aortic root reoperation.
4.1. Operative mortality
Mortality for acute type A aortic dissection varies between 15% and30% [3]. It remains high with little changes through time, despite recenttechnical advances reflecting the severity of the disease itself. Fann et al.[8] reported, in a large series, a 26% 30-daymortality rate and one of theinitial publications from the international registry of acute aortic dissec-tion (IRAD) reported a 27% 30-day mortality rate [9]. Lately, data fromthe latter registry showed a 23% and a 63% 30-day mortality rate in pa-tients with and without mesenteric malperfusion, respectively [10].Fujimatsu et al. [11], who also divided their cohort into two groups(SCR vs. Bentall), did not find any significant difference in operativemortality. Similarly, Niclauss et al., [7] in a selected young population(b40 years), found no significant difference in mortality between thetwo surgical techniques. ARS is usually considered as a more complexand demanding operation than SCR. In our study, surprisingly, wefound a lower mortality rate in the ARS group. Despite longer times ofcross-clamp and CPB in this group, postoperative complications
dom from proximal reoperation among the groups.
Table 6Proximal reoperations' rates for acute type A aortic dissection in the recent literature.
Pessotto et al. [15] 99/34 15/0 5Sabik et al. [1] 135/0 4/0 4.7Gelsomino et al. [17] 0/19 0/0 7.2De Paulis et al. [2] 41/0 17/0 5Fujimatsu et al. [11] 33/12 18/0 3Niclauss et al. 13/14 23/0 9.7Consistre et al. [18] 173/61 6/0 4.7Malvindi et al. [19] 95/13 21/8 6.5Bekkers et al. [14] 157/49 8/0 7.2Present study 144/82 10/2 9.1
289I. Hysi et al. / International Journal of Cardiology 184 (2015) 285–290
including neurological complications or peripheral malperfusions werenot different between the groups. Similarly, the ICU and hospital lengthsof stay were also not significantly different. These results suggest thatthe occurrence of a complication is related to the gravity of the primarydisease and not due to the surgical complexity of the procedure. Fur-thermore our findings suggested that a complete resection of the prox-imal diseased aorta did not burden immediate results.
There is still debate about the value of an “age cut-off” for patientsundergoing surgery for acute type A aortic dissection [12], howeverresults from surgery remains superior to those from medical treat-ment until the age of 80 [13]. Nevertheless, the importance of ageand its impact on operative mortality should not be underestimated.Like others before, we showed that it is an important prognostic fac-tor per se; in our study every decade of age tenfold increased themortality risk.
We observed more right coronary artery bypasses in the ARS group,but without affecting in-hospital mortality. Although these coronary is-sues were all related to the dissecting process itself, this technical pointrepresents the Achilles' heel of the Bentall procedure, especially duringan acute aortic dissection.
4.2. Long-term survival and proximal reoperations
Bekkers et al. [14] reported a 15-year survival, which included oper-ative mortality, of 37%. Notably, the authors noted that this late survivalwas comparable with the survival of an age-matched German cohort ofpatients undergoing an aortic valve replacement with a mechanicalprosthesis. In our cohort, the 15-year survival, which excluded opera-tivemortality, was 69%with a significant difference between the groups(SCR 62.6% vs. ARS 82.8%). ARS in our series has given patients a “near”normal lifespan after an acute aortic “accident”.
In the absence of aortic root replacement, when there is no preoper-ative aortic regurgitation, 10% of patients will develop later significantaortic insufficiency, while among patients who have preoperative aorticregurgitation, 39%will develop severe postoperative aortic insufficiency[15]. Others [14,15] have reported that proximal reoperation rates werehigher in patientswithworse thanmild grade preoperative aortic insuf-ficiency. In our study, we did not observe the same link between aorticinsufficiency and late proximal reoperations (data not shown). Butmostof the time in our practice ARS was preferred in case of significant pre-operative aortic regurgitation (Table 1). This strategy has also probablycontributed to the reduction of the number of late reoperations on theaortic root.
Commonly, the false lumen remains circulating in 50–70% of patients.Gariboldi et al. [16] identified the Bentall procedure and anticoagulationtreatment as risk factors for patency of the false lumen but its thrombosisafter surgery remains unpredictable. Our study was not designed to an-alyze the influence of ARS on the patency of the aortic false lumen, buton the other hand the negative impact of a lifelong anticoagulation
treatment could suggest the routine use of a bioprosthetic valve duringBentall procedures for acute type A aortic dissection even in young pa-tients. Biological Bentall will avoid anticoagulant treatment. The ab-sence of a mechanical valve will facilitate further TEVAR proceduresand in case of early bioprosthesis degeneration a transapical TAVRwith a valve-in-valve procedure could be proposed.
4.3. Limitations of our study
The major limitation of our study is its retrospective nature and theabsence of a clear surgical strategy regarding the aortic root. Further-more the ARS group was more young and recent in our study as a con-sequence of evolution of our surgical strategy with time, thus it mighthas induced a bias in our analysis.
4.4. Conclusion
Our study suggests the value of a complete aortic root replacementfor acute type A aortic dissection. This aggressive surgical strategy hasreduced the rate of late proximal reoperations with acceptable postop-erative outcomes and whether it has to be systematically preferred inyounger patient has to be demonstrated. Furthermore awider use of bi-ological Bentall or valve sparing operation in younger patient to avoid alifetime anticoagulant treatment or to facilitate further endovascularprocedure has also to be further studied.
Funding
None.
Conflicts of interest
None to declare.
References
[1] J.F. Sabik, B.W. Lytle, E.H. Blackstone, P.M. McCarthy, F.D. Loop, D.M. Cosgrove, Long-term effectiveness of operations for ascending aortic dissections, J. Thorac.Cardiovasc. Surg. 119 (2000) 946–962.
[2] R. De Paulis, E. Cetrano, M. Moscarelli, et al., Effects of ascending aorta replacementon aortic root dilatation, Eur. J. Cardiothorac. Surg. 27 (2005) 86–89.
[3] R.S. Bonser, A.M. Ranasinghe, M. Loubani, et al., Evidence, lack of evidence, contro-versy, and debate in the provision and performance of the surgery of acute type Aaortic dissection, J. Am. Coll. Cardiol. 58 (2011) 2455–2474.
[4] E. Neri, M. Massetti, G. Capannini, et al., Axillary artery cannulation in type a aorticdissection operations, J. Thorac. Cardiovasc. Surg. 118 (1999) 324–329.
[5] N. Simon-Kupilik, H. Schima, L. Huber, et al., Prosthetic replacement of the aorta is arisk factor for aortic root aneurysm development, Ann. Thorac. Surg. 73 (2002)455–459.
[6] M.A. Ergin, J. McCullough, J.D. Galla, S.L. Lansman, R.B. Griepp, Radical replacementof the aortic root in acute type A dissection: indications and outcome, Eur. J.Cardiothorac. Surg. 10 (1996) 840–844.
[7] L. Niclauss, D. Delay, L.K. von Segesser, Type A dissection in young patients, Interact.Cardiovasc. Thorac. Surg. 12 (2011) 194–198.
[8] J.I. Fann, J.A. Smith, D.C. Miller, et al., Surgical management of aortic dissection dur-ing a 30-year period, Circulation 92 (1995) II113–II121.
[9] P.G. Hagan, C.A. Nienaber, E.M. Isselbacher, et al., The International Registry of AcuteAortic Dissection (IRAD): new insights into an old disease, JAMA 283 (2000)897–903.
[10] M. Di Eusanio, S. Trimarchi, H.J. Patel, et al., Clinical presentation, management, andshort-term outcome of patients with type A acute dissection complicated bymesen-teric malperfusion: observations from the International Registry of Acute Aortic Dis-section, J. Thorac. Cardiovasc. Surg. 145 (2013) 385–390 (e1).
[11] T. Fujimatsu, H. Osawa, S. Osaka, F. Takai, M. Hashimoto, H. Suzuki, Strategies fortreatment of acute aortic dissection with involvement of sinus of valsalva, Ann.Thorac. Cardiovasc. Surg. 15 (2009) 382–388.
[12] G.H.L. Tang, R. Malekan, C.J. Yu, M. Kai, S.L. Lansman, D. Spielvogel, Surgery for acutetype A aortic dissection in octogenarians is justified, J. Thorac. Cardiovasc. Surg. 145(2013) S186–S190.
[13] S. Trimarchi, K.A. Eagle, C.A. Nienaber, et al., Role of age in acute type A aortic dissec-tion outcome: report from the International Registry of Acute Aortic Dissection(IRAD), J. Thorac. Cardiovasc. Surg. 140 (2010) 784–789.
[14] J.A. Bekkers, G.B. Raap, J.J.M. Takkenberg, A.J.J.C. Bogers, Acute type A aortic dissec-tion: long-term results and reoperations, Eur. J. Cardiothorac. Surg. 43 (2013)389–396.
290 I. Hysi et al. / International Journal of Cardiology 184 (2015) 285–290
[15] R. Pessotto, F. Santini, P. Pugliese, et al., Preservation of the aortic valve in acute typeA dissection complicated by aortic regurgitation, Ann. Thorac. Surg. 67 (1999)2010–2013.
[16] V. Gariboldi, D. Grisoli, F. Kerbaul, et al., Long-term outcomes after repaired acutetype A aortic dissections, Interact. Cardiovasc. Thorac. Surg. 6 (2007) 47–51.
[17] S. Gelsomino, G. Morocutti, R. Frassani, et al., Long-term results of Bentall compositeaortic root replacement for ascending aortic aneurysms and dissections, Chest 124(2003) 984–988.
[18] G. Concistrè, G. Casali, E. Santaniello, et al., Reoperation after surgical correction ofacute type A aortic dissection: risk factor analysis, Ann. Thorac. Surg. 93 (2012)450–455.
[19] P.G. Malvindi, B.P. van Putte, U. Sonker, R.H. Heijmen, M.A.A.M. Schepens, W.J.Morshuis, Reoperation after acute type a aortic dissection repair: a series of 104 pa-tients, Ann. Thorac. Surg. 95 (2013) 922–927.
