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Ann Thorac Surg 2006;81:2063-2078
© 2006 The Society of Thoracic Surgeons
a Cardiovascular Surgery Service, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas
b Division of Cardiothoracic Surgery, Baylor College of Medicine, Houston, Texas
c Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, Houston, Texas
Accepted for publication January 13, 2006.
* Address correspondence to Dr LeMaire, One Baylor Plaza, BCM 390, Houston, TX 77030 (Email: slemaire{at}bcm.tmc.edu).
Presented at the Fifty-first Annual Meeting of the Southern Thoracic Surgical Association, Cancun, Mexico, Nov 4–6, 2004.
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Abstract |
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METHODS: During a 16-year period, 300 patients with presumed Marfan syndrome underwent 398 operations on the aorta and branch arteries, including 125 aortic root operations, 59 aortic arch repairs, 31 descending thoracic aortic repairs, and 178 thoracoabdominal aortic repairs. Based on medical record review, patients were classified as confirmed Marfan syndrome if documented features satisfied current diagnostic criteria; patients not meeting these criteria were classified as suspected Marfan syndrome.
RESULTS: There were 17 operative deaths (4.3%) after the 398 operations. Survival after the initial referral operation was 96.2% ± 1.5% at 1 year, 82.7% ± 2.4% at 5 years, and 74.6% ± 3.1% at 10 years. Presentations, operative details, and outcomes were remarkably similar in the 137 patients (45.7%) with confirmed Marfan syndrome and the 163 patients (54.3%) with suspected Marfan syndrome. Freedom from repair failure, however, was significantly better in patients with confirmed Marfan syndrome (90.3% ± 2.3% at 10 years) than in those with suspected Marfan syndrome (82.0% ± 3.1% at 10 years; p = 0.001).
CONCLUSIONS: Operative treatment of the full spectrum of aortic disease in Marfan patients enables excellent long-term survival. Similarities in surgical aspects of aortic disease suggest that patients with features of Marfan syndrome who do not meet diagnostic criteria should be managed in the same manner as patients with confirmed Marfan syndrome.
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Introduction |
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Although the majority of patients in this series were referred with a Marfan diagnosis, upon review of the documented features of MFS, many did not meet current diagnostic criteria [11]. Although accurate diagnosis of MFS has extremely important genetic and clinical implications, whether it impacts aortic treatment is unclear. To address this issue as a secondary objective, we examined the impact of accurate MFS diagnosis on surgical aspects of aortic disease, including presentation, operative management, and outcome.
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Patients and Methods |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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All patients who were referred with the diagnosis of MFS were included in the analysis; however, for each patient, the presumed MFS diagnosis was scrutinized based on thorough review of the patient's medical records. Patients were classified as confirmed MFS only if documented manifestations satisfied the current Ghent criteria for diagnosis [11]. Patients who did not meet these criteria were classified as suspected MFS.
Surgical procedures were classified as emergent if surgery was required imminently because of an acute life-threatening condition; urgent if surgery was required during the same hospitalization because of deterioration in clinical status; and elective if the patient's aneurysm was stable at the time of surgery, such that the procedure could be delayed without serious risk. Dissections were considered acute if surgical intervention occurred within 14 days of the onset of symptoms; otherwise they were labeled chronic. Patients were characterized as symptomatic if they had any symptom (severe or mild) related to their aortic disease, including pain, hoarseness, dysphagia, and dyspnea.
Operative mortality was defined as death occurring within 30 days of surgery or during the initial hospitalization. Deaths that occurred beyond this early period were classified as late mortality. Stroke was defined as any new clinically or radiographically evident brain injury present after operation, including focal and global deficits, and transient and permanent deficits. All patients with lower extremity neurologic deficits not attributable to stroke were defined as having paraplegia (paralysis) or paraparesis (weakness) regardless of whether the deficit was immediate or delayed, transient or permanent. Cardiac complications were defined as myocardial infarction, atrial or ventricular arrhythmia requiring treatment, pericardial effusion requiring drainage, or cardiac failure requiring inotropic support greater than 48 hours, intraaortic balloon counterpulsation, or mechanical ventricular support. Pulmonary complications were defined as ventilatory support greater than 48 hours, respiratory insufficiency requiring reintubation, adult respiratory distress syndrome, atelectasis requiring bronchoscopy, chylothorax, prolonged air leak, pneumonia, or pleural effusion or pneumothorax necessitating tube thoracostomy. Acute renal dysfunction was defined as a doubling of serum creatinine (relative to baseline).
As a means of assessing durability of surgical repair, we defined repair failure as the development of any pseudoaneurysm or true aneurysm (such as a patch aneurysm) involving the previous repair site, reoperation for graft infection, and severe aortic valve dysfunction (native or prosthetic) after aortic valve or root surgery. The development of a true aneurysm adjacent to a previous repair was attributed to progression of disease and not considered repair failure. Repair failures were recorded for both outside operations and those performed at BCM.
Patients
Aortic operations were performed in 300 patients with presumed MFS during a 16-year period. Demographic and preoperative characteristics of these patients at the time of initial referral to our institution are presented in Table 1. Patient ages ranged from 11 to 73 years (mean, 39 ± 12 years). On the basis of current diagnostic criteria [11], 137 patients (45.7%) had confirmed MFS and 163 (54.3%) had suspected MFS (did not meet criteria).
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Aortic Root Operations
Details regarding 125 aortic root operations are presented in Table 4. Most operations (77%) were performed using cardiopulmonary bypass with moderate hypothermia. Profound hypothermic circulatory arrest was used for all patients with acute ascending aortic dissection (DeBakey types I and II) or aortic arch aneurysms. There were no ruptured aneurysms. Twenty patients with previous graft replacement of the tubular segment of the ascending aorta required reoperation for root replacement as a result of subsequent dilatation of the sinus segment; 7 of these patients had confirmed MFS and 13 had suspected MFS. Mechanical composite valve grafts were used for root replacement (Fig 1) in the majority of operations (n = 89, 71%); valve-sparing root replacement (reimplantation technique) or tissue root replacements were used in 35 operations (28%). One patient underwent primary repair of a perivalvular pseudoaneurysm after prior composite valve graft placement. In 84 operations (67%), both coronary arteries were reattached using the button technique. The classic Bentall technique was used in 3 operations. When adequate mobilization of the coronary arteries was difficult because of an extremely large aneurysm or scarring from previous operation, a variety of alternative coronary reattachment techniques were used, including single Cabrol graft to both coronary ostia (23 operations), button reattachment of the left main coronary artery and saphenous vein interposition graft to the right coronary artery (5 operations), button reattachment of the right coronary artery and polyester interposition graft to the left main coronary artery (5 operations), individual polyester interposition grafts to both coronary ostia (3 operations), and button reattachment of the right coronary artery and Bentall-type reattachment of the left main coronary artery (1 operation). The most common concomitant operation was aortic arch replacement (26 operations, 21%), which is described in the following section.
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Other Proximal Aortic Operations
Twelve proximal aortic operations did not involve the aortic root or arch. Operations were performed in 4 patients with confirmed MFS and 8 patients with suspected MFS, and included ascending aortic repair in 8, aortic valve replacement in 3, and aortic valve replacement with mitral valve repair in 1. Nine procedures (75%) were reoperations after previous aortic repairs; 2 procedures (17%) involved repairs of pseudoaneurysms, 3 (25%) involved correction of aortic valve insufficiency, and 1 involved repair of a recurrent ascending aortic aneurysm. In 2 patients with prior aortic root operations and severe pectus deformity, aortic valve replacement was performed through a left anterior thoracotomy [23]. Two patients—1 with confirmed MFS and 1 with suspected MFS—underwent ascending aortic repair with aortic valve resuspension in the setting of acute aortic dissection; these were both performed early in the series.
Descending Thoracic Aortic Operations
There were 31 descending thoracic aortic (DTA) repairs (Table 5). Most were performed without left heart bypass, cerebrospinal fluid drainage, or intercostal artery reattachment. Cardiopulmonary bypass and hypothermic circulatory arrest were only used when aortic clamping was not possible (5 operations) owing to aortic rupture or because the size of the distal arch was too large. Three patients with pseudoaneurysms involving the descending thoracic portion of TAAA grafts underwent endoluminal coverage of the pseudoaneurysms using stent grafts. Two patients with suspected MFS were referred after unsuccessful DTA endograft procedures. One of these patients required removal of an infected endograft with aortic debridement and ligation (she had previously undergone right axillary–femoral bypass). The other patient required endograft removal and graft replacement of the DTA during hypothermic circulatory arrest.
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Abdominal Aortic Operations
Abdominal aortic aneurysm repairs were performed in 6 patients. Three of the patients had aneurysms (without dissection) involving the infrarenal aorta distal to previous TAAA repairs. These were treated with open graft repair in 2 patients. An endovascular graft was used in 1 patient; the distal end of the TAAA graft was used as the proximal landing zone. One patient with chronic aortic dissection underwent graft replacement of large infrarenal aortic and bilateral iliac aneurysms. One patient underwent graft repair of a juxtarenal aortic aneurysm. The final patient presented with a mycotic pseudoaneurysm involving the suprarenal aorta, which was managed by resection and patch repair using bovine pericardium.
Statistical Analysis
Statistical analysis was conducted with SPSS and SAS software (SPSS Institute, Inc, Chicago, IL, and SAS Institute Inc, Cary, NC). For comparative evaluations, Fisher's exact tests were used for categorical variables and Student's t test was used for continuous variables. Actuarial Kaplan–Meier probability curves were created to demonstrate medium-term and long-term survival and freedom from repair failure; curves were compared using the log-rank test. Values of p less than 0.05 were considered significant.
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Results |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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Aortic Arch Operations
Table 7 presents the results for 59 aortic arch operations. There were five operative deaths (8%); causes of death were cardiac failure (n = 2), stroke (n = 1), sepsis or multiple organ failure (n = 1), and bleeding from a mycotic pseudoaneurysm (n = 1). Early complications included stroke after five operations (8%). There was one repair failure. Five-year survival after aortic arch operation was 74.3% ± 6.0%.
Other Proximal Aortic Operations
There were no operative deaths or strokes after these 12 operations. There have been three subsequent repair failures (25%), including one perivalvular leak after aortic valve replacement to treat a failed valve-sparing root reconstruction. Both patients with aortic valve resuspension exhibited valve insufficiency and sinus dilatation that required reoperation to correct the progressive aortic root disease. All 3 patients with repair failures were alive at last follow-up.
Descending Thoracic Aortic Operations
Results of 31 DTA operations are presented in Table 8. There were two operative deaths (6%), one as a result of sepsis and multiple organ failure and one as a result of bleeding from a mycotic pseudoaneurysm. Both patients who underwent DTA repair in the setting of acute aortic dissection survived. One patient with acute dissection exhibited immediate paraplegia. One patient had a myocardial infarction. There were no strokes after DTA repair. The 3 patients who underwent endoluminal coverage of descending thoracic pseudoaneurysms after prior TAAA repair recovered without paraplegia or other complications; all 3 were alive at latest follow-up. The patient who required removal of an infected DTA endograft died of sepsis and multiple organ failure. The other patient who underwent DTA endograft removal recovered without complications and was alive at last follow-up. There have not been any repair failures after DTA repair.
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Confirmed Versus Suspected Marfan Syndrome
At the time of initial referral, the two groups exhibited similar patient characteristics (Table 1), with the exception of hypertension, which was less common in patients with confirmed MFS than in those with suspected MFS. The numbers of operations per patient were similar (Table 3), with 2.2 ± 1.2 operations per patient in the confirmed MFS group and 2.3 ± 1.1 operations per patient in the suspected MFS group (p = 0.5).
Patients with confirmed MFS were more likely to have acute symptoms at the time of aortic arch operation, and consequently had fewer elective arch repairs (Table 4). Patients with suspected MFS had a higher incidence of acute renal dysfunction after arch operations (Table 7). All other perioperative details and outcomes for proximal aortic operations were similar in the confirmed and suspected MFS groups (Tables 4, 7).
Aortic clamp times during DTA repair were longer in the suspected MFS group, but clamp times during TAAA repair were similar in the two groups (Table 5). All three endovascular operations to treat repair failures in the DTA were performed in patients with confirmed MFS. Patients with suspected MFS were more likely to have a bypass graft placed to the left renal artery during TAAA repair. All other perioperative characteristics for distal aortic repairs were similar and there were no differences in outcomes (Tables 5, 8).
Mid-term and long-term survival after the initial referral operation were similar (Fig 2B). Although the incidence of repair failures was similar in the two groups, freedom from repair failure was significantly better in the confirmed MFS group (Fig 2D).
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Comment |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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Although all of the patients in this series were previously considered to have MFS or a related disorder, more than half did not meet current diagnostic criteria [11]. This series covers a 16-year period, during which the diagnostic criteria for MFS have changed [11]. Our evolving understanding of the genetics and pathobiology of MFS make further revisions in diagnostic criteria inevitable [1, 3, 25]. In most cases, MFS results from mutations in the gene for fibrillin-1 (FBN1), which is a major component of microfibrils within the aortic extracellular matrix; however, the relationship between FBN1 mutations and the phenotypic manifestations of MFS is neither sensitive nor specific [3, 25]. Fibrillin-1 mutations, for example, can cause other, non-MFS conditions, such as MASS phenotype (myopia, mitral valve prolapse, aortic dilatation, skin and skeletal involvement) and familial thoracic aortic aneurysm and dissections [26, 27]; patients with these disorders have aortic disease, but do not meet current diagnostic criteria for MFS despite the presence of an FBN1 mutation. Katzke and colleagues [28] found FBN1 mutations in 12% of patients with manifestations suggestive of MFS but not fulfilling current diagnostic criteria. Conversely, mutations involving genes other than FBN1 have been identified in patients who meet clinical criteria for MFS. For example, 1 patient with extensive aortic involvement in this series (8 aortic or branch artery operations) satisfies the Ghent criteria (he has major skeletal involvement and dural ectasia) but has a missense mutation in the transforming growth factor-ß receptor type II gene (TGFBR2) [unpublished data, 25, 29]. Although initial data on patients with TGFBR2 mutations suggests that the aortic disease should be aggressively managed, the ideal treatment of aortic disease in patients with conditions that overlap with MFS has not been specifically delineated. To begin to address this issue, we examined the impact of accurate MFS diagnosis on the surgical aspects of aortic disease, including presentation, operative management, and outcome.
Overall, the characteristics of surgical aortic disease were similar in patients with confirmed and suspected MFS. Important similarities included the prevalence of aortic dissection, the number of operations required, the extent of aortic replacement, the need for a variety of concomitant procedures, and the use of protective adjuncts. The majority of outcomes were also similar, including operative mortality, major early complications, the incidence of repair failure, and long-term survival. Surprisingly, patients with confirmed MFS remained free of repair failure longer than patients with suspected MFS. One potential explanation is that some patients with non-Marfan connective tissue disorders may have a more severe form of aortic disease, making repair failure more likely. TGFBR2 mutations can cause familial forms of thoracic aortic aneurysms and dissections, but can also cause more severe aortic disease than is typically observed in MFS patients. A long-term, prospective study comparing repair failures in patients with MFS versus those with other disorders is needed to confirm our findings and to evaluate the potential causes.
Several surgical techniques have been developed in attempt to prevent repair failure; the more frequent application of these techniques in patients with confirmed MFS might reduce the incidence of long-term failures. For example, because progressive aneurysmal dilation of the aortic sinuses is inevitable when the aortic valve and ascending aorta are replaced separately in MFS patients, aortic root replacement is widely accepted as the treatment of choice for Marfan ascending aortic disease. The preferred approach to coronary reattachment in these patients remains the button technique, which allows for direct, tension-free reattachment and minimizes postoperative bleeding and pseudoaneurysm formation [8]. Several alternative techniques (eg, Cabrol or individual interposition grafts) can enable tension-free anastomoses when mobilization of the coronary buttons is impractical, such as in patients who require reoperation or have very large aneurysms. This approach to aortic root replacement appears to offer satisfactory durability, as demonstrated by the 88.4% ± 4.3% 5-year freedom from repair failure. The data reported herein suggest that these strategies are also warranted in patients with suspected MFS who do not meet diagnostic criteria.
The objectives of minimizing the amount of residual aortic tissue and creating tension-free anastomoses also apply to distal aortic repairs, especially when reattaching intercostal and visceral or renal arteries as patches. The majority of patients who had TAAA repairs in this series underwent visceral vessel reattachment using the patch technique. Experiences with subsequent patch dilation and pseudoaneurysms have recently led us to increase the use of separate branch grafts to the individual visceral and renal ostia in MFS patients [30, 31, 32].
Concerns regarding durability of aortic repair are particularly relevant to two evolving surgical techniques: valve-sparing aortic root replacement and aortic endografts. The issue of whether valve-sparing aortic root replacement leads to improved surgical outcomes in MFS patients with annuloaortic ectasia is unresolved. Although bleeding and thromboembolic complications may be reduced after the valve-sparing technique, concerns remain regarding the long-term durability of this type of repair [6, 33, 34]. In the current series, valve-sparing root replacements resulted in half of the repair failures that occurred after root operations. We are currently conducting an international, multicenter study to prospectively compare the results of valve-replacing versus valve-sparing aortic root reconstructions. The use of endovascular stent grafts in patients with MFS has clear limitations [35]. Because the entire aorta is affected by MFS, fixation zones for endografts are invariably diseased and, therefore, prone to future dilatation resulting in dangerous endoleaks. When conversion to open repair is required, the need to remove a failed endograft increases the complexity of the aortic reconstruction. Endografts, however, may be well-suited for excluding focal pseudoaneurysms in these patients when an existing aortic graft can be used for the proximal and distal landing zones [3].
With increased survival, ongoing cardiovascular connective tissue involvement often leads to consecutive surgeries. This underscores the palliative nature of cardiovascular repair in these patients and the need for lifetime follow-up. Our current surveillance strategy includes obtaining an initial follow-up computed tomographic scan within 3 months of surgery, followed by yearly scans thereafter. Scans are obtained more frequently in patients with evidence of progressive aortic expansion. This follow-up strategy also applies to patients with "total" aortic replacement because they remain at risk for developing pseudoaneurysms and patch aneurysms.
This retrospective study spanning more than 16 years has important limitations. Deficiencies in documentation made confirmation of MFS difficult in many patients; this problem cannot be rectified in patients who have since died or have become lost to follow-up. Furthermore, because MFS is often an evolving diagnosis, patients in the suspected MFS group who were lost to follow-up may have developed additional manifestations that would now confirm the diagnosis. The relative rarity of MFS—with a prevalence of 1 in 3,000 to 5,000 in the general population—has limited the experience of treating the associated cardiovascular complications primarily to large specialized centers. The inherent difficulty in generalizing single-center reports supports the need for future, large-scale research endeavors that combine data from multiple centers. Such studies will further clarify the role of major aortic surgery in patients with MFS as well as those with overlapping connective tissue disorders.
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Discussion |
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TopAbstractIntroductionPatients and MethodsResultsCommentDiscussionAcknowledgmentsReferences |
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DR COSELLI: That is a good question. Although there is only one prospective randomized trial looking at it, we recommend to all of our patients to use ß-blockers, trying to use the benefit of ß-blockers, even in the face of a relatively normal blood pressure. The data on that are based on growth of the aortic root, primarily in children. There are no hard data in the distal aorta, but because of the pathology being so similar, ß-blockers continue to be our long-term drug of choice.
DR CONSTANTINE MAVROUDIS (Chicago, IL): That was a very nice presentation, Joe. I wonder, what was the youngest patient with Marfan syndrome for whom you used the inclusion technique? And how small a graft would you use under those circumstances? I imagine that it would depend on somatic growth potential, but what are your guidelines for that in terms of treating someone without aortic insufficiency who has Marfan syndrome and an enlarging aneurysm but in whom you are performing a valve-sparing operation?
DR COSELLI: Quite fortunately, most patients with Marfan syndrome at a younger age are large for size based on what one would expect. I also, in order to truly answer your question, am able to somewhat dodge it, because our particular institution is an adult institution and we are blessed with having Texas Children's Hospital and Chuck Fraser next door, and he is the one who treats the younger patients and the children with Marfan syndrome and is probably better prepared to answer that question than I.
DR JOHN M. KRATZ (Charleston, SC): I enjoyed your talk, Dr Coselli. We recently had an opportunity to see one of your patients from many years ago whose ascending aorta is doing great. He now has mitral insufficiency, and I wonder if you could address how often you are seeing significant mitral insufficiency in this group of patients and what you think the appropriate surgical intervention for them would be?
DR COSELLI: Fifteen to 20%, and mitral valve repairs in the Marfan patient have held up over the long term and continue to be our primary choice.
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