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Aortic Root Disease after the Ross Procedure
Q&A with Prof. Alessandro Mazzucco, MD., University of Verona, Verona, Italy
By Andrea Massa
Dear Professor, the choice of Ross procedure in the treatment of aortic valve disease has shown several advantages, especially in young adult patients. Survival rate and quality of life improvements have proved satisfactory after the operation but not totally without risks. Late morbidity may in fact be substantial.
It may seem a paradox but the dreaded complications associated with deterioration of right-heart conduits have shown prevalence and severity much lower than expected and usually lended themselves to relatively easy percutaneous treatment.
On the contrary, pathology of the autograft root and valve has emerged in a percentage of cases as the true vulnerable point late after the procedure.
Nowadays, an accurate estimate of prevalence of autograft root disease is limited by lack of uniform definition of critical dilatation or aneurysm. Given the undefined prognostic and therapeutic implications for patients falling within this spectrum of disease, it seems prudent to include in the risk analysis a range of pathological dimensions greater than 4 cm, but smaller than 5 or 5.5 cm. which can hardly be identified as aneurysm, but can certainly be labeled as dilatation. A second factor is the variability in methods used to scrutinize patient populations. Many of the clinical series dealing with this end-point use cross-sectional analysis. However, cross-sectional echocardiographic or MRI scanning may lead to underestimate true prevalence of root disease. Ideally, longitudinal investigation with serial measurements for each patient at risk would lead to accurate definition of neoaortic root dilatation.
Given that, prevalence of significant dilatation at any one or more of the 4 left ventricular outflow tract levels ranges from 10 to over 30% of late survivors.
Such estimates, in spite of a much lower incidence of dysfunction, result in disappointingly low actuarial freedom from dilatation ranging from 42% to 45% at 7 years, in populations including a majority of free standing root replacement (47% in our experience vs 15% subcoronary, 38% inclusion). This, it must be emphasized once more, in the face of a much higher freedom from dysfunction.
There are reports suggesting root dilatation may not occur, even in the setting of total root replacement. What's your view in that respect?
It's true but, nonetheless, it is interesting to observe how average and range values of autograft root diameters measured are incredibly similar, if not identical, in most clinical series when corrected for length of follow-up. This finding may suggest that Authors who have found lower or even negligible prevalence of root dilatation after operation are destined to witness a significant increase in this complication as longer follow-up is gathered.
Strictly intertwined with variable prevalence of root pathology after the Ross procedure is variability in recognized risk factors among the different clinical reports, isn't this the case?
No randomized, prospective trial exists on this theme, nevertheless root replacement technique represents the only recurrent risk factor for late dilatation among the various clinical series. On the contrary, demonstration that subcoronary and inclusion cylinder grafting are rarely, if ever, afflicted by root dilatation lends further support to the findings above, which represents our experience as well. A series of explanations has been proposed to account for dilatation of free-standing autograft roots.
Structural characteristics of human pulmonary roots in adults, including thickness of media layer, orientation and fragmentation of elastic fibres, make it intrinsically different from the aortic root and explain differences in mechanical properties.
On the contrary, young infants, in whom structure of aortic and pulmonary roots are similar as a result of the pressure load, are less exposed to pathological dilatation of autograft roots. Furthermore, devascularization and, possibly, denervation of pulmonary artery wall retained in the root replacement technique may accelerate aspecific degenerative findings, such as cystic medial necrosis and elastic fiber fragmentation, uniformly encountered in explanted autografts. Thus, the likely destiny of otherwise unsupported free-standing autograft roots is to dilate with time, probably starting some 5-8 years after implant.
Have other risk factors for dilatation been identified?
Preoperative aneurysmal pathology of the native aortic wall has been found to predict late dilatation of the autograft, in our experience, as well as in the one of others. Female gender has not been universally acknowledged. It must be said that some reports, combining pediatric and adult population, have suggested that younger age may be associated with root dilatation, possibly due to higher prevalence of root mismatch and root replacement technique in children. This finding, however, has not been uniformly confirmed. Thus, whether patients undergoing the procedure during early infancy will be protected from this complication long-term remains to be definitively proven, due to small numbers and incomplete echocardiographic follow-up available at present.
Recognized degenerative and inflammatory connective tissue disorders are obviously a risk factor for both valve failure and root pathology, and, as such, represent absolute contraindication to the procedure. Rheumatic valve disease, a common indication to the Ross operation in developing countries, besides causing valve dysfunction due to relapse, has recently also been associated with root dilatation.
The most controversial risk factor with regards to the Ross operation is the bicuspid aortic valve disease. Are patients affected by it more exposed than others to a late dilatation of the autograft or more in general to a root dilatation?
The association between bicuspid aortic valve and pathological findings of the media layer of aortic root and ascending aorta has long been recognized. Clinical observations from the University of Toronto have suggested that congenital aortic valve lesions (mainly bicuspid) may predispose to late dilatation of the autograft. Furthermore, pathological studies from the same group have shown degenerative changes in the pulmonary artery media of patients with bicuspid aortic valve. These results have led to speculate on common developmental error responsible for aortic and pulmonary valve disease, which may affect bicuspid valve patients undergoing the Ross operation. In spite of this intriguing hypothesis, clinico-pathological and molecular biological studies on actual Ross patients, carried out at our and other institutions, have failed to confirm the findings from Toronto. In addition, most clinical series have ruled out the fact that bicuspid aortic valve patients may intrinsically be more exposed to root dilatation. In summary, the vast majority of laboratory and clinical evidence supports the contention that degenerative changes found in explanted autograft roots are the result of acquired (exposure to systemic pressure, ischemia due to loss of vasa vasorum, denervation) rather than congenital factors.
Among the consequences of root disease, has the recurrent regurgitation still regarded as the most insidious one?
This clearly seems not to be the case and dilatation appears to be the almost invariable consequence of root disease. Some studies have even quantified the yearly growth rate. Variability in pace of progression exists within the same clinical series, based on operative technique (greatest with root replacement), patient gender (female) and preoperative diagnosis (aortic insufficiency), but also among different clinical series. In patients eventually requiring root reoperation, in fact, Takkenberg and associates have observed maximum dilatation rates of 0.7 mm/year, which contrast with our findings of rates as high as 3 mm/year in the same subset of patients. Initially, it was widely believed that only dilatation of sinotubular junction would promote autograft valve insufficiency, due to splaying of valve commissures. More recently, it has been recognized that even dilatation of the sinus of Valsalva portion, when it exceeds 30% of normal diameter, causes valve insufficiency due to stretching and flattening of leaflets. Magnetic resonance imaging of the aorta late after Ross operation has identified three distinct morphological patterns; tubular, divergent and convergent dilatation, associated with subcoronary, inclusion and root replacement technique, respectively.
Furthermore, it has been documented that both divergent (i. e. sinotubular junction level) and convergent (i. e. sinus of Valsalva level), but not tubular, dilatation can generate autograft valve regurgitation.
Do other complications of dilatation also exist, which are less common than progression toward aneurysm formation and valve regurgitation?
Isolated reports of autograft root dissection, rarely concomitant with native ascending aortic dissection, have appeared in the literature. This complication may be subtle when dissection is limited to the autograft root, due to absence of pain at presentation, possibly resulting from to denervation. Furthermore, if aneurysmal autografts can dissect, risk of rupture in this setting is probably greater than what originally hypothesized. Therefore, cautious stands, which advocated reintervention on autograft root aneurysm only after development of valve regurgitation, have currently been abandoned in favor of a more aggressive approach.
Experience with medical treatment of autograft root dilatation is, even if limited, seldom reported. Management guidelines derive from clinical practice with native aortic root aneurysm. Accordingly, more recently use of beta-receptor antagonist and angiotensin-converting enzyme inhibitors has been proposed. Do you agree with such approach?
Clinical and experimental evidence tends to support use of these drugs. However, definition of outcome in terms of decrease in growth rate in Ross patients is still lacking.
Similarly to native aortic aneurysm, the mainstay of therapy for autograft root pathology remains surgery. Given the original expectation of a durable, if not definitive, operation on the left side of the heart and, at the same time, considering the mistakengly projected need for reoperation on the right ventricular outflow tract, the approach to autograft root dilatation has initially been very conservative. Practically, indications to elective resection of autograft aneurysm were delayed until onset of relevant valve insufficiency.
Two circumstances, however, have forced to reconsider such a treatment strategy. Firstly, evidence that autograft aneurysms are exposed to the same complications of native aneurysms, namely dissection and rupture. More recently, the proven ability to successfully resect the aneurysm sparing the autologous pulmonary valve which had previously believed rather unlikely. Currently, indications to elective reintervention include any patient with at least one root diameter equal or greater than 5.0 cm (0.26 cm/m2 when indexed for BSA), regardless of the presence of valve dysfunction. Our institutional approach has been to apply the same criteria recently proposed by Svensson and associates for prohylactic aneurysm resection in asymptomatic Marfan and bicuspid aortic valve patients: aortic root area (r2π[cm2])/height (m) > 10.
Following this more aggressive policy, success rate of autograft root remodeling with valve preservation, always the goal of reoperation on Ross patients, has been over 75% of patients treated at the University of Verona.
In cases of structural valve pathology associated to dilation, has your team performed traditional surgical management of autograft root pathology combined with composite or aortic homograft root replacement using the modified Bentall technique? How was it treated?
We applied the technique of valve-sparing surgery - mostly using the so called Yacoub operation - to autograft aneurysm involving sinuses up to 7 patients in our current experience. Their early outcome has been rewarding, without hospital mortality and no more than mild residual valve regurgitation at discharge. However, average clinical and echocardiographic follow-up of these patients does not exceed the 2 year-landmark. It is thus premature to judge the stability of the repair as relates to autograft valve function.
A granted dilatation limited to the sinotubular junction and proximal ascending aorta can be successfully dealt with by resection and interposition of undersized Dacron grafts. Risk of this type of reoperation, appears low, if not negligible and it might be seen as a very reasonable alternative to the price to be payed for an only hypothetically more predictable and stable functional result which is represented by morbidity connected with cardiac valve prostheses, particularly worrisome when considering the specific requirements of most Ross patients: growth, employment, physical activity, pregnancy.
Some literature ( Sievers) and practice have shown that subcoronary technique in skilled hands offers excellent mid-term functional outcome and absence of root dilatation. What's your experience in this field?
Experimental studies at our institution using magnetic resonance imaging in long-term Ross survivors demonstrate that subcoronary grafting allows preservation of physiological autograft root elasticity and valve operation supporting Sievers' clinical observations. Use of cylinder inclusion technique, which shares with root replacement the ability to obtain a fully competent autograft valve, may be limited by gross aortic-pulmonary root mismatch. In addition, physiological properties of the native aortic root are not maintained, possibly due to the effect of double aortic wall.
Practically, many institutions performing the Ross procedure, including our own, have become more selective with regards to indications in adults, thereby explaining the decline in operations performed yearly world-wide. When resorting to the Ross procedure, it has recently become our current policy to use subcoronary grafting, or more rarely, cylinder inclusion in adults: root replacement is still the standard in growing children.
A number of alternative strategies to control prevalence of late autograft dilatation have also been proposed, mostly aimed at supporting or stabilizing the free-standing root. Based on our experimental findings with magnetic resonance imaging, loss of compliance and altered valve dynamics can be expected in a proportion of these patients due to the impact of a double aortic wall layer.
The result of prophylactic blood pressure control in the first three months after operation is much debated as few if none of the young patients undergoing the Ross procedure are hypertensive and the effect of maintaining subnormal blood pressure remains entirely speculative, at present.
References
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