Late Echocardiographic Study of Aortic Valve and Aortic Root after Surgery for Type A Acute Aortic Dissection.

OBJECTIVE: In case of concomitant aortic regurgitation (AR) valve, sparing operation is considered the first choice in selected patients. The aim of this retrospective clinical and echocardiographic study was to evaluate the long-term survival results of conservative approach and the determinants of recurrent AR.
METHODS: From 2000 to 2011, fifty patients (median: 63 years and interquartile range: 53-72) underwent an aortic valve-sparing procedure for acute aortic dissection, and discharged alive. The long-term clinical and echocardiographic outcome was analyzed.
RESULTS: Late all-causes mortality was 18% (nine patients) at a median follow-up of 55.8 months. Ten patients (20%) underwent re-operations, five of them for aortic valve/root recurrent disease; freedom from proximal re-operation was 90%. Two-third of the patients had a preoperative AR grade <3; a non-negligible number of patients with acute significant AR (23% with grade ≥3) at the time of surgery underwent conservative aortic valve surgery. At a median echocardiographic follow-up of 50.5 months, we found no significant correlation between late recurrent AR and AR grade at the time of surgery and the aortic root diameter. Late recurrent AR grade was significantly higher in patients who underwent aortic commissures and cusps resuspension than those who underwent lone ascending aorta replacement (2.29 ± 1.05 vs. 1.58 ± 1.03, P = 0.028).
CONCLUSIONS: Preoperative AR and late aortic root diameter were not the predictors of late AR. Late AR is higher in patients who underwent aortic commissures and cusps resuspension compared to the only replacement of the ascending aorta.

INTRODUCTION

Stanford type A acute aortic dissection (AAD) is a challenge due to high mortality risk in acute phase.[12] During the last decades, thanks to diagnostic[3] and intensive care improvements, evolving surgical techniques, and perioperative management, the early mortality rate has progressively decreased, as confirmed in a recent Italian Registry.[45]

More attention has recently raised in reducing the incidence of late complications and avoiding re-operations.[67] AAD is often associated with a variable degree of concomitant aortic valve regurgitation (AR); emergency surgery has to also address the aortic valve function.[89] The choice between either conservative approach or replacement of the aortic valve is crucial and basically relies on the degree of aortic root involvement, aortic valve morphology, and the underlying mechanism of AR.

Effective aortic valve repair results in the maintenance of proper hemodynamics, avoiding the consequences of prosthetic valve such as endocarditis, thromboembolism, and chronic anticoagulation.[1011] On the other hand, aortic valve preservation exposes patients to a theoretically increased risk of aortic root late complications;[12] besides late root aneurysms or pseudoaneurysms, recurrence of AR is the most frequent cause of re-operation. Long-term echocardiographic surveillance in patients with preserved aortic valve is mandatory.[13]

We performed a clinical and echocardiographic retrospective study in patients operated on an emergency basis for AAD with the preservation of aortic native valve to evaluate the overall survival, the long-term results of aortic valve conservative surgery, and the determinants of recurrent AR.

METHODS

After obtaining approval by the Local Ethical Committee, we retrospectively collected data on fifty patients [median age: 63 years and interquartile range (IQR): 53–72; Table 1] who underwent surgical operation for AAD, between 2000 and 2011, and discharged alive. None of the fifty patients had Marfan syndrome.

Table 1

Demographic data

	Number	Median (%)	Interquartile range
Age (years)		63	53-72
<70	34	68
≥70	16	32
Male gender	35	70
BAV	3	6
Marfan syndrome	0	0
Hypertension	42	84
Renal impairment	4	8
Previous cardiac surgery	3	6

BAV=Bicuspid aortic valve

Surgical techniques

All operations were performed by trained staff cardiovascular surgeons, and all patients underwent conservative aortic valve surgery.

After the induction of anesthesia, the surgery was preceded by transesophageal echocardiography (TEE) to assess preoperative AR and the anatomy of the aortic root. Surgery was accomplished in deep hypothermia and circulatory arrest. Myocardial protection was achieved by cold blood retrograde cardioplegia, and neurological protection was improved by selective anterograde cerebral perfusion.

With regard to operative techniques, the patient was treated with different surgical operations:

Twenty-six patients (52%) underwent ascending aorta replacement alone with prosthetic graft, with proximal anastomosis at the sinotubular junction; inclusion criteria were a normal aortic root and a morphologically normal aortic valve, not prolapsing

Nineteen patients (38%) with dissected aortic root but apparently normal aortic valve underwent ascending aorta replacement and reconstruction of the diseased sinuses by biological glue and concomitant resuspension of prolapsing aortic cusp

Four patients (8%) with most severe dissection of one or more Valsalva sinuses but apparently normal aortic valve underwent replacement of pathological sinuses of Valsalva, with a specifically tailored vascular graft to replace the severely affected sinuses

One patient (2%) with localized dissection of atherosclerotic ascending aorta underwent adhesion of the aortic wall layers with biological glue, without replacement of ascending aorta.

Echocardiographic analysis

Echocardiographic follow-up was completed in June 2014, at a median follow-up time of 50.5 months (IQR: 25.2–82.5, at a maximum of 167 months); all patients had an echocardiographic assessment at least after 3 months after discharge. Two-dimensional color Doppler transthoracic echocardiography (TTE) was performed, and standard variables were collected according to the JASE/EACVI dataset.

The degree of AR was classified in a 4-grade scale. For patients requiring re-operation, last TTE immediately before the operation was considered.

Clinical follow-up

Data regarding survival and re-operation rate were obtained by the departmental and outpatients clinic database, by phone contacts with referral cardiologist or general practitioners, and by phone call to patient or family. Median clinical follow-up time was 55.8 months (IQR: 17.6-93.2, at a maximum of 167 months).

Statistical analysis

Data are expressed as mean and standard deviation, or median and IQR (IQR I-III), when appropriate, or percentage (%). Comparison between continuous variables was performed with Spearman test (nonparametric), while comparison between groups was tested by Mann–Whitney U-test (nonparametric). Statistical analysis was computed using SPSS, version 17.0 for Windows® (SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant.

RESULTS

Mortality and re-operations

Late all-causes mortality was 18% [Figure 1]; the median interval time between deaths and surgery for AAD was 59 months (IQR: 47–104).

Figure 1

Survival curve of Kaplan–Meier estimate (all-causes mortality)

After a median of 25 postoperative months (IQR: 17-89), ten patients (20%) underwent re-operation: Five (10%) for distal aortic disease (arch pseudoaneurysm and thoracic endovascular aortic repair), and five patients (10%; after 2, 5, 7, 8, and 9 years) due to severe recurrent AR. No patients who undergone root re-operation died.

Due to the small number of patients in redo-group, we could only provide a descriptive analysis of preoperative AR grade, late AR grade, and late aortic root diameter [Figure 2a and b].

Figure 2

Patients with or without proximal re-operation (5 vs. 45, mean ± standard deviation). Box (a) descriptive analysis of aortic regurgitation grade; AR = Aortic regurgitation. Box (b) descriptive analysis of late aortic root diameter

Predictors of aortic valve regurgitation

Late echocardiographic data are reported in Table 2. Seventy-seven percent of the patients had a preoperative AR grade <3; thus, a non-negligible number of patients with an acute significant AR (23% with grade ≥3) at the time of surgery underwent conservative aortic valve surgery, in terms of simple ascending aorta replacement (40%) or resuspension of aortic cusp with commissuroplasty/reconstruction of pathological sinuses of Valsalva (60%).

Table 2

Late echocardiographic data

	Median (%)	Interquartile range
Echocardiographic follow-up (months)	50.5	25.2-82.5
AR follow-up (grade)	1.75	1-2.5
<3	82
≥3	18
IVS (mm)	12	10-13
LVEDD (mm)	52	49-58
LVEDV (ml)	118	85-157
LVEF (%)	57	50-62
<50	19
≥50	81
Aortic root (mm)	39	36-43

AR=Aortic regurgitation, IVS=Interventricular septum, LVEDD=Left ventricular end-diastolic diameter, LVEDV=Left ventricular end-diastolic volume, LVEF=Left ventricular ejection fraction

We evaluated the relationship between recurrent AR at follow-up and two variables: Preoperative AR and late aortic root diameter. Neither preoperative AR nor late aortic root diameter were the significant predictors of recurrent late AR (P values of 0.14 and 0.09, respectively).

We analyzed our population according to the surgical technique: Ascending aorta replacement with or without aortic root procedure and aortic valve resuspension. The median preoperative AR grade was 1 (1–3) and 1 (1–2), respectively. Late recurrent AR grade was significantly higher among patients who underwent cusp resuspension [2.29 ± 1.05 vs. 1.58 ± 1.03, P = 0.028; Table 3].

Table 3

Relationship between late aortic regurgitation grade and surgical technique

	Number	Mean	SD	P
Resuspension	19	2.29	1.05	0.028
Simply replacement of ascending aorta	26	1.58	1.03

SD=Standard deviation

DISCUSSION

Emergency surgery of AAD is a lifesaving procedure; the main aims are: First, prevention of acute death and second, prevention of late sequelae. Thus, many studies evaluated the predictors of death to determine the optimum surgical strategy.[1415]

In the present study, all-causes mortality in survivors after discharge was 18% with the longest follow-up reaching almost 14 years. Our data confirm an acceptable mortality rate in more recent decades.[16]

Long-term complications after AAD surgery include aneurysm of the residual aorta, anastomotic pseudoaneurysm, and recurrent AR after conservative approach to the aortic valve and aortic root. In the treatment of acute AR in this scenario, conservative methods gained popularity[8] because they avoid the complications of prosthetic valve. The decreasing hospital mortality and better long-term survival have potentially increased the sequelae of AAD, particularly in terms of late recurrence of AR.

From this point of view, the role of both clinical and echocardiographic follow-up is crucial. According to our retrospective analysis, freedom from proximal re-operation for aortic root or valve diseases was 90%; re-operations themselves showed good results in terms of hospital mortality and morbidity. The main issues related to aortic valve repair in AAD is avoiding valve prosthesis versus the risk of re-operation for late recurrent AR. Casselman et al. reported a freedom from aortic root re-operation of 89%, 5 years after conservative surgery[10] and Mazzucotelli et al. indicated a freedom from aortic valve replacement of 83% at 5 years.[17] Finally, Saczkowski et al. in a recent review observed a linearized late mortality rate of 4.7%/patient-year and a late aortic valve reintervention rate after initial repair of 2.1%/patient-year, with a freedom from aortic valve reintervention of 89% at 5 years.[9] Conservative aortic valve procedures are, also in our experience, an appropriate surgical approach with good long-term results. However, we have to consider that these results were obtained in a single center on a selected group of patients for which conservative techniques appeared ultimately appropriated.

The issues of predictors and determinants of late recurrent AR are controversial. We focused on the pathogenic mechanisms of late AR, especially on aortic root dimensions measured at late TTE. Our data interestingly revealed that recurrent AR was not associated with the intrinsic parameters of aortic root, thus not just related to the pathological mechanism causing root dilatation.

Furthermore, several studies stressed the relevance of preoperative AR on patients outcome: Pessotto et al. concluded that preservation of the aortic valve is associated to an increased risk of recurrent AR in patients presenting with moderate-to-severe AR;[18] Yamanaka et al. showed that high-grade preoperative AR improved during the postoperative follow-up after valve preservation with root reconstruction;[7] on the contrary, Bekkers et al. demonstrated that the aortic valve preservation in patients with severe preoperative AR was associated with an increased risk of aortic valve re-operation.[6] In our experience, late AR was not related to preoperative AR obtained by TEE, so greater preoperative AR grade was not a predictor for late AR. Furthermore, a worse outcome in patients with high preoperative AR grade was not confirmed; between the six patients with preoperative severe AR, conservatively treated, only one patient presented moderate recurrent AR at follow-up and another one presented severe AR due to late endocarditis.

On the other hand, late AR was significantly influenced by surgical technique; patients who underwent the aortic cusp resuspension showed a significantly higher AR at the follow-up compared to those who underwent the replacement of the ascending aorta alone. The changes of the aortic root geometry due to the surgical approach, which is obviously affected by the extent of dissection, seemed to play a role in the development of late AR. It is known that aortic competence depends on the correct balance between the elements of the single unit consisting of the aortic root and cusps;[19] moreover, this unit can undergo long-term changes if conservative techniques are performed.

Despite the retrospective nature of our study, we would speculate pathogenic mechanisms in the development of late AR. A supposed bystander is the biological glue which was widely used; since its introduction, surgical mortality decreased because it reinforced fragile tissues, provided hemostasis, and reduced the time required for surgery.[202122] However, its cytotoxicity is unknown and several reports described the disadvantages of using glue such as the high rates of re-operation for redissection and recurrent aortic sinus aneurysm formation,[2324] the risk of aortic wall necrosis,[25] and the possible increased difficulty of a surgical procedure at re-operation.[21] If the risk of aortic root redissection is well known, data about the effects of glue on late aortic competence are scarce. von Oppell et al. concluded that biological glue used to repair dissected sinuses and combined with resuspension aortic valve is associated with a high recurrence rate of AR on follow-up;[23] other authors registered the high AR incidence after the use of glue.[24]

According to our results, the use of glue in the dissected aorta wall of the root, with a higher amount in patients who underwent aortic cusp resuspension, was associated with the greater incidence of recurrent AR. Nevertheless, on the basis of our results, we cannot blame the glue as a cause of recurrent AR; rather, its use in the dissected root may be considered as an expression of extremely severe derangement of the aortic wall of the root, secondary to acute dissection itself.

The observation that the aortic root diameter is not a causative mechanism for late AR should carry out focalized researches on prospective TTE after surgery and dedicated views to measure the aortic annulus and its ratio with prosthesis/sinotubular junction.

Limitations

The first limitation is the retrospective nature of the study and the absence of dedicated echocardiographic views for annulus measurements in all patients. Second, we could not analyze data about other surgical techniques, even more invasive on the aortic root, such as the reconstruction of the sinuses of Valsalva or David procedures, due to the small number of patients. Finally, an intraoperative quantitative evaluation of biological glue will be necessary to confirm our hypothesis about its role in the development of late AR.

CONCLUSIONS

Simple aortic valve resuspension seems to be effective in the long-term period, with low incidence of late AR and re-operation. Preoperative AR and aortic root diameter were not the predictors of late AR, while AR is higher in patients who underwent cusp resuspension compared to the only replacement of the ascending aorta, unmasking the possible impact of greater acute derangement of the aortic root secondary to a more severe AAD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.