Author + information
- D. Craig Miller, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. D. Craig Miller, Department of Cardiovascular Surgery, Stanford University Medical School, FALK CV Research Center ULN, 300 Pasteur Drive, Stanford, California 94305.
The paper in this issue of the Journal by Ouzounian et al. (1) at the Toronto General Hospital (TGH) is noteworthy for the superb surgical results achieved after valve-sparing aortic root replacement (V-SARR) compared with propensity-matched cohorts receiving valve replacement using a composite valve graft (CVG), with either a biological valve (bio-CVG) or a mechanical valve (m-CVG), over a 20-year interval (1990 to 2010) (1). This group, under the leadership of Dr. Tirone David, is widely respected for their cardiovascular surgical excellence, comprehensive patient follow-up (including frequent serial follow-up echocardiograms), honest reporting, and strict adherence to the 2008 American Association for Thoracic Surgery/Society of Thoracic Surgeons/European Association for Cardio-Thoracic Surgery valve-reporting guidelines (2) (including the composite endpoint major adverse valve-related events and categorizing all sudden, unexplained deaths as valve-related). This work is strengthened by the input of their expert biostatistician, Cedric Manlhoit, including new sophisticated competing-risk statistical techniques and reporting all adverse events (except all-cause mortality) as cumulative incidence rates, also known as the observed cumulative frequency or, more familiar to clinicians, the actual incidence, in contrast to the more commonly seen Kaplan-Meier actuarial incidence. Using the Kaplan-Meier actuarial method for nonfatal complications can be misleading (usually overestimating the estimated incidence) because it censors patients when they die or are lost to follow-up (assuming all subjects live forever), and assumes that the competing risks of dying and complications are independent (3).
There was no difference in the extraordinarily low in-hospital mortality and stroke rates (0.3% and 1%, respectively, for all 616 patients) among the 3 subgroups. The 15-year Kaplan-Meier all-cause mortality estimates were similar (16%, 24%, and 25% for the V-SARR, bio-CVG, and m-CVG cohorts, respectively; p = NS in the adjusted multivariable analysis). Adjusting for all covariates, the cumulative incidence rates of cardiac mortality, major adverse valve-related events, reoperation (REOP), and anticoagulation-related hemorrhage were all lower for the V-SARR cohort. Specifically, the REOP cumulative incidence for the bio-CVG patients was very high (20 ± 4% at 15 years), indicating that if V-SARR is not judged advisable by the surgeon, choosing a tissue valve CVG for aortic root replacement in these very young patients is not prudent, even in the era of potential valve-in-valve transcatheter aortic valve replacement when structural valve deterioration occurs. It was not surprising that the lowest 15-year cumulative incidence of REOP of all 3 groups was in the m-CVG cohort (1 ± 1%), but anticoagulation-related hemorrhage occurred more frequently (12 ± 3% at 15 years). It would be informative to learn what international normalized ratio target range these investigators recommended for the m-CVG patients (all received St. Jude Medical bileaflet valves), because many clinicians usually aim for an international normalized ratio only in the 1.5 to 2.0 range, with aspirin supplementation for young m-CVG patients with bileaflet valves who are in sinus rhythm. Although not a prospective randomized trial, this rigorous, retrospective, comparative, sophisticated analysis allowed the investigators to conclude that V-SARR “is the treatment of choice for young patients with aortic root aneurysms and normal or near-normal aortic cusps” and that “…potential candidates for AVS [aortic valve sparing] should be referred to larger, experienced centers and not receive a CVG as the default operation” (1). In my opinion, these conclusions are overstated and somewhat misleading.
To interpret these results in proper context, it is important to note first that the study cohort represented a very highly selected population of young, very low-risk patients undergoing elective operations. Patients older than 70 years of age and those with aortic stenosis, type A aortic dissection, endocarditis, and undergoing nonelective operations were excluded, such that all patients were theoretically eligible for either operative procedure. The carefully selected 616 patients represented 52% of the total of 1,187 aortic root replacements done at the TGH during this period, for an average annual volume of 59 aortic root replacement cases, which is exceptionally high (these are very experienced thoracic aortic surgeons). Indeed, the TGH magnet for young patients with aortic root pathology really is Dr. David, who personally performed 76% of the 3 types of procedures in this series (and 90% of the 253 V-SARR operations). Despite this single-surgeon dominance, there was no significant interaction among the 3 surgeons and early or late outcomes in this analysis. As Ouzounian et al. (1) mention, the STS database report by Stamou et al. (4) (2004 to 2010; N = 13,743; excluding type A dissection and endocarditis, only 14% received a V-SARR) revealed that the average number of aortic root replacements performed was only 2 per center in 2009, with only 5% of sites performing more than 16 procedures that year. This statistic is sobering, and makes it clear that the experience and expertise at the TGH are exceptional; it is unrealistic to expect that the results of V-SARR described in this paper (1) can be duplicated broadly. Although the V-SARR results at the TGH certainly meet the standard promulgated by the U.S. National Marfan Foundation (V-SARR procedures should only be performed in centers where the operative mortality is <1% and the 10-year freedom from valve reoperation exceeds 90%) (5), it is unlikely that many hospitals can achieve this goal, save a small number of high-volume referral centers with special expertise in thoracic aortic surgery. Although the personal results of Dr. David, a master surgeon and father of the “David reimplantation V-SARR procedure,” are unmatched and may never be equaled elsewhere, this remains a strong bias when one ponders if the TGH results are generalizable. As the investigators state, “our results with AVS operations have been exceptionally good, largely because of surgical expertise and the fact that most of our patients had normal or near-normal aortic cusps” (1). What an understatement—Amen!
The only prospective, controlled, large investigation with core laboratory-adjudicated imaging comparing V-SARR with CVG is the AVOMP (Aortic Valve Operative Outcomes in Marfan Patients Study) registry, sponsored by the National Marfan Foundation, which enrolled 316 nonrandomized patients with Marfan syndrome between 2005 and 2010 at 19 centers in North and South America and Europe (5). It was concerning that 7% of patients in the V-SARR group had developed ≥2+ residual or recurrent aortic regurgitation by 1 year (5). All patients will be followed until at least 2021, when the minimum follow-up time will exceed 10 years. This is essential if we are to learn where V-SARR ultimately fits into the armamentarium, who should do it, and where it should be performed. More troubling are numerous recent publications from several experienced centers who have broadened the indications and report freedom from ≥2+ recurrent aortic regurgitation or REOP rates after V-SARR for various types of aortic root disease that are suboptimal (6–12), and markedly inferior to the TGH outcomes (1). Furthermore, most other reports do not contain enough patients remaining at risk at 10 years and beyond to be confident about the long-term prognosis.
It must be remembered that V-SARR and CVG are not competing procedures; they are complementary. At Stanford, the ratio of CVG to V-SARR for all pathologies (any valve lesion, elective or emergency) over the last 23 years was 2:1; when one considers all 1,187 elective aortic root-replacement procedures between 1990 and 2010 at the TGH, a bio-CVG was used in 47%, m-CVG in 29%, and V-SARR in 24% of cases, for a CVG/V-SARR ratio of 3.2:1. In contrast, among the 616 low-risk elective aneurysm patients selected specifically for their potential candidacy for V-SARR in this report, a bio-CVG was used in 29% of patients, m-CVG in 30%, and a V-SARR was actually performed in only 41% (CVG/V-SARR ratio of 1.4:1). This means the surgeon judged that V-SARR was not in the patient’s best interest in 59% of procedures.
What no propensity score can adjust for is seasoned surgical judgment determining which procedure is best for each individual patient. This subjective factor may be the main reason why the long-term results reported here by Ouzounian et al. (1) are so outstanding. Surgical judgment is key. This is why I disagree with the wording of the investigators’ strong conclusions. What they probably meant to say is that their analysis supports V-SARR as the best treatment when a very experienced surgeon determines it is the best option, and not in every young patient with a root aneurysm. The corollary is that potential candidates for V-SARR should at least be given the opportunity to meet and discuss their surgical options with an experienced thoracic aortic surgeon who has a proven track record doing either operation, and not that no patient should ever receive a CVG.
Therefore, for now, the decision cardiologists face in deciding where to refer their young patients with aortic root aneurysmal disease (including those with Marfan syndrome), for elective operative repair should be predicated on the documented post-operative track record and annual aortic root surgery volume in regional cardiovascular surgical centers with special expertise and ample experience in both these operations. V-SARR is one procedure that should not be performed on an occasional basis by low-volume surgeons; as always is the case, proper patient selection is paramount and the chief determinant of outcome.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Miller has reported that he has no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Ouzounian M.,
- Rao V.,
- Manlhiot C.,
- et al.
- Coselli J.S.,
- Volguina I.V.,
- LeMaire S.A.,
- et al.,
- for the Aortic Valve Operative Outcomes in Marfan Patients Study Group