Prophylactic Aortic Root Replacement Research Articles

Growth of the aortic root in children and young adults with Marfan syndrome

ObjectivesThe primary aim was to gain insight into the growth of the aortic root in children and young adults with Marfan syndrome (MFS). Furthermore, we aimed to identify a clinical...

Aortic root surgery in Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant connective disease etiologically related with FBN-1 gene mutation. The altered microfibril protein structure result in characteristic cardiovascular abnormalities including aortic root dilatation, aortic root aneurysms, and aortic dissections. Aortic root aneurysms and subsequent dissection are the major causes of reduced life expectancy in MFS patients. Prophylactic aortic root replacement has improved the survival of patients with MFS. Elective root replacement carries very low mortality and morbidity. Emergency root replacement for dissection is accompanied with higher early mortality and late deaths/interventions. Both the techniques of aortic root replacement, total root replacement (TRR) with a prosthetic valved conduit, and valve-sparing root replacement (VSRR) yield excellent early and late results. Considering the low risk of prosthetic valve-related events, the improved long-term survival, and event-free survival, TRR continues to be a very effective surgical option. VSSR also seems to be a good option for the first 10 to 15years following surgery in MFS patients. The choice of procedure depends upon available expertise, patients' choice, feasibility of anticoagulation, possibility of pregnancy, and lifestyle of the patient. Aortic root morphology and state of valve cusps also affect the decision making. In recent times, personalized external aortic root support (PEARS) with a macroporous mesh sleeve has also emerged as a promising alternative to aortic root replacement. All these patients need close monitoring for whole life after surgical intervention.

Associations of Age and Sex With Marfan Phenotype: The National Heart, Lung, and Blood Institute GenTAC (Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) Registry.

The associations of age and sex with phenotypic features of Marfan syndrome have not been systematically examined in a large cohort of both children and adults. We evaluated 789 Marfan patients enrolled in the National Heart, Lung, and Blood Institute GenTAC (Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) Registry (53% male; mean age 31 [range: 1-86 years]). Females aged ≥15 and males aged ≥16 years were considered adults based on average age of skeletal maturity. Adults (n=606) were more likely than children (n=183) likely to have spontaneous pneumothorax, scoliosis, and striae but were comparable in revised Ghent systemic score, ectopia lentis, and most phenotypic features, including prevalence of aortic root dilatation. Prophylactic aortic root replacement and mitral valve surgery were rare during childhood versus adulthood (2% versus 35% and 1% versus 9%, respectively, both P<0.0001). Adult males were more likely than females to have aortic root dilatation (92% versus 84%), aortic regurgitation (55% versus 36%), and to have undergone prophylactic aortic root replacement (47% versus 24%), all P<0.001. Prevalence of previous aortic dissection tended to be higher in males than females (25% versus 18%, P=0.06); 44% of dissections were type B. Type B dissection was strongly associated with previous prophylactic aortic root replacement. Pulmonary, skeletal, and aortic complications, but not other phenotypic features, are more prevalent in adults than children in Marfan syndrome. Aortic aneurysms and prophylactic aortic surgery are more common in men. Aortic dissection, commonly type B, occurs in an appreciable proportion of Marfan patients, especially in men and after previous prophylactic aortic root replacement.

Peripartum type B aortic dissection in patients with Marfan syndrome who underwent aortic root replacement: a case series study.

To investigate pregnancy outcomes, especially the risk of pregnancy-related aortic dissection (AD), in patients with Marfan syndrome (MFS) after prophylactic aortic root replacement (ARR). Retrospective case series study. Tertiary perinatal care centre at a university hospital. Pregnant women fulfilling the revised Ghent nosology (2010) criteria for MFS who were managed at our institute. The pregnancy outcomes of all patients with MFS managed at our institute between 1982 and September 2016 were reviewed retrospectively based on medical records. Obstetrical management and complication including the incidence of AD throughout the peripartum period. Among 22 patients (28 pregnancies) who had been managed as potential MFS or related disorders, 14 (17 pregnancies) fulfilled the revised Ghent nosology (2010) criteria for MFS and were enrolled in this study. Five patients (five pregnancies) had received ARR before conception: three (60%) developed type B aortic dissection [AD(B)] during the peripartum period, compared with only one of 10 patients (12 pregnancies) without ARR (P<0.05, Chi-square test). Our study results suggest that MFS patients after prophylactic ARR are still at high risk of AD(B) during the peripartum period. Careful pre-pregnancy counselling and multidisciplinary care throughout the peripartum period are essential for the management of MFS, even after surgical repair of an ascending aortic aneurysm. MFS patients after prophylactic ARR are still at high risk of type B aortic dissection during the peripartum period.

Aortic Root Replacement for Children With Loeys-Dietz Syndrome

Loeys-Dietz syndrome (LDS) is an aggressive aortopathy with a proclivity for aortic aneurysm rupture and dissection at smaller diameters than other connective tissue disorders. We reviewed our surgical experience of children with LDS to validate our guidelines for prophylactic aortic root replacement (ARR). We reviewed all children (younger than 18 years) with a diagnosis of LDS who underwent ARR at our institution. The primary endpoint was mortality, and secondary endpoints included complications and the need for further interventions. Thirty-four children with LDS underwent ARR. Mean age at operation was 10 years, and 15 (44%) were female. Mean preoperative root diameter was 4 cm. Three children (9%) had composite ARR with a mechanical prosthesis, and 31 (91%) underwent valve-sparing ARR. Concomitant procedures included arch replacement in 2 (6%), aortic valve repair in 1 (3%), and patent foramen ovale closure in 16 (47%). There was no operative mortality.Two children (6%) required late replacement of the ascending aorta, 5 (15%) required arch replacement, 1(3%) required mitral valve replacement, and 2 (6%) had coronary button aneurysms/pseudoaneurysms requiring repair. Three children required redo valve-sparing ARR after a Florida sleeve procedure, and 2 had progressive aortic insufficiency requiring aortic valve replacement after a valve-sparing procedure. There were 2 late deaths (6%). These data confirm the aggressive aortopathy of LDS. Valve-sparing ARR should be performed when feasible to avoid the risks of prostheses. Serial imaging of the arterial tree is critical, given the rate of subsequent intervention.

Abstract 11615: Influence of Age and Gender on Marfan Phenotype: The NHLBI GenTAC Registry

Background: The influence of gender and age on phenotypic features of individuals with Marfan syndrome has not been systematically examined in a large cohort of both children and adults. Methods: We evaluated 789 Marfan patients enrolled in the NHLBI GenTAC Registry (53% male; mean age 31 [range: 1-86 years]). Females aged≥15 and males aged≥16 years were considered adults based on average age of skeletal maturity. Results: Children (n=183) and adults (n=606) (see Table) were comparable in revised Ghent systemic score, ectopia lentis, and most phenotypic features, including prevalences of aortic root dilatation and mitral prolapse. However, adults were more likely to have spontaneous pneumothorax, scoliosis, dural ectasia and striae. Prophylactic aortic root replacement and mitral valve surgery were rare during childhood vs. adulthood (2 vs. 35% and 1 vs. 9%, respectively, both p&lt;0.0001). There was only one childhood aortic dissection (type B in 15 year old male). Overall females were more likely than males to have arachnodactyly (54 vs. 40%), scoliosis (60 vs. 49%), and dural ectasia (16 vs. 10%), all p&lt;0.01. Adult males were more likely to have aortic root dilatation (92 vs. 84%), aortic regurgitation (55 vs. 36%) and to have undergone prophylactic aortic root replacement (47 vs. 24%), all p&lt;0.001. Prevalence of prior aortic dissection was higher in males than females (25 vs. 18%, p=0.06), 44% of which were type B. Mean age at dissection (35 vs. 38 years), age at prophylactic surgery (32 vs. 35 years), and need for mitral valve surgery (9.5 vs. 10.0%) were similar between men and women, respectively. Conclusions: Pulmonary, skeletal and aortic complications, but not other phenotypic features, increase with aging in Marfan syndrome. Aortic aneurysms and prophylactic aortic surgery are more common in men. In the era of current surgical and medical treatment, aortic dissection, commonly type B, occurs in an appreciable proportion of Marfan patients, especially among men.

P5 Aortic dilatation in repaired tetralogy of fallot: Features, determinants and progression

Background We examined the features, determinants and rate of progression related to aortic dilatation in adults with repaired tetralogy of Fallot (rTOF). Methods and Results One-hundred-and-ten adults with rTOF and native aorta, baseline median age 30.9 (IQR22.9–39.4) years were assessed by serial cardiovascular magnetic resonance (CMR), and over a median follow-up of 6.3 (IQR5.1–7.6) years. Aortic dimensions were measured at sinus, sinotubular junction (STJ) and mid-ascending aortic level. Dilatation was defined as diameter >2 standard deviations larger than normal for the age. Seventy-six patients (69%) had aortic dilatation, of which 27% at sinus, 66% at STJ, and 21% had ascending aortic level (figure 1). Baseline predictors of aortic dilatation were male gender and previous history of palliation. Forty-seven percent had increase in aortic diameters, 25% at sinus, 21% at STJ and 35% at ascending aortic level, at a rate of 0.05 ± 0.1, 0.06 ± 0.14 and 0.12 ± 0.26 mm/year respectively. Predictors of aortic diameter increase at STJ level were older age, later repair and right aortic arch. No predictors of aortic diameter increase at other levels were ascertained. Conclusions Aortic dilatation was observed in two thirds of our adult with rTOF patients, affecting not only the aortic root but the ascending aorta as well. However, the rates of progression were very low. These data do not support frequent aortic assessment in follow-up and aggressive prophylactic aortic root replacement.

Bentall procedure: quarter century of clinical experiences of a single surgeon

BackgroundWe retrospectively analyzed 25 years of experiences with the button Bentall procedure in patients with aortic root pathologies. Even though this procedure has become widespread, there are only a few very long term follow-ups available in the clinical literature, especially regarding single surgeon results.MethodsBetween 1988 and 2013, a total of 147 patients underwent the Bentall procedure by the same surgeon. Among them there were 62 patients with Marfan syndrome. At the time of the surgery the mean age was 46.5 ± 17.6 years. The impact of surgical experience on long-term survival was evaluated using a cumulative sum analysis chart.ResultsThe Kaplan-Meier estimated overall survival rates for the 147 patients were 91.8 ± 2.3 %, 84.3 ± 3.1 %, 76.3 ± 4.9 % and 59.5 ± 10.7 % at 1,5,10 and 20 years, respectively. Multivariate Cox regression analysis identified EuroSCORE II over 3 % (OR 4.245, 95 % CI, 1.739–10.364, p = 0.002), acute indication (OR 2.942, 95 % CI, 1.158–7.480, p = 0.023), use of deep hypothermic circulatory arrest (OR 3.267, 95 % CI, 1.283–8.323, p = 0.013), chronic kidney disease (OR 6.865, 95 % CI, 1.339–35.189, p = 0.021) and early complication (OR 3.134, 95 % CI, 1.246–7.883, p = 0.015) as significant risk factors for the late overall death. The survival rate for freedom from early complication was 94.3 ± 2.2 %, 88.0 ± 3.3 %, 82.9 ± 4.7 % and 69.2 ± 8.4 % at 1,5,10 and 20 years. The main pathological findings of the aortic wall were cystic medial degeneration in 75 %, fibrosis in 6 %, atherosclerosis in 13 % and no pathological alteration in 6 % of the samples. The overall survival rate was significantly lower in patients operated in first 15 years compared to patients operated in the last decade (log-rank p = 0.011).ConclusionAccording to our long-term follow-up the Bentall operation provides an appropriate functional result by resolving the lesions of the ascending aorta. Based on our results, 25–30 operations done is necessary to gain such a level of confidence and experince to aquire better results on long-term survival. In addition, we discussed that there were no co-morbidities affecting on the survival of Marfan patients and prophylactic aortic root replacement ensures a longer survival among patients with Marfan syndrome.

Facial and Ocular Features of Marfan Syndrome

Marfan syndrome is the most common inherited disorder of connective tissue affecting multiple organ systems. Identification of the facial, ocular and skeletal features should prompt referral for aortic imaging since sudden death by aortic dissection and rupture remains a major cause of death in patients with unrecognized Marfan syndrome. Echocardiography is recommended as the initial imaging test, and once a dilated aortic root is identified magnetic resonance or computed tomography should be done to assess the entire aorta. Prophylactic aortic root replacement is safe and has been demonstrated to improve life expectancy in patients with Marfan syndrome. Medical therapy for Marfan syndrome includes the use of beta blockers in older children and adults with an enlarged aorta. Addition of angiotensin receptor antagonists has been shown to slow the progression of aortic root dilation compared to beta blockers alone. Lifelong and regular follow up in a center for specialized care is important for patients with Marfan syndrome. We present a case of a patient with clinical features of Marfan syndrome and discuss possible therapeutic interventions for her dilated aorta.

Diagnosis and treatment of Marfan syndrome: an update

> But in no regard was he more peculiar than in his personal appearance. He was singularly tall and thin. He stooped much. His limbs were long and emaciated. His...

Losartan treatment in adult patients with Marfan syndrome: can we finally COMPARE?

This editorial refers to ‘Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial’[†][1], by M. Groenink et al. , on page 3491 Marfan syndrome (MFS)1 is an autosomal dominant connective tissue disorder with a prevalence of ∼1 in 5000 individuals. The syndrome results from mutations in the fibrillin-1-encoding gene ( FBN1 ).2 As >600 mutations in FBN1 have been reported, a great variety of phenotypes are encountered. Hence, MFS is a systemic disorder which may differently affect the cardiovascular, ocular, and musculoskeletal systems. The cardiovascular manifestations, including progressive aortic root dilatation, or aortic dissection or rupture, are the leading cause of mortality in MFS. Myxomatous mitral valve changes may also be present and contribute to an adverse outcome.3 The diagnosis of MFS continues to rely on a clinical assessment, as molecular testing for FBN1 mutations is neither sensitive nor specific. Accordingly, the established Ghent criteria4 use a combination of clinical findings in the various organ systems, the family history, and an FBN1 mutation to make the diagnosis of MFS. Currently, the medical management of MFS patients employs serial cardiac imaging studies to measure aortic dimensions and pharmacological treatment to reduce the haemodynamic stress on the aortic wall. Once the aortic diameter reaches a certain threshold, prophylactic aortic root replacement, either by a composite valve graft repair or by an aortic valve-sparing operation, is undertaken. This strategy has extended the average life expectancy from ∼40 years before the era of open heart surgery, up to ∼70 years in patients with MFS.5 However, in spite of this progress, morbidity in patients with MFS remains high as the great majority will suffer an adverse cardiovascular event, such as surgical repair of the aortic root, fatal or non-fatal aortic dissection, or mitral valve surgery. The pharmacological … [1]: #fn-2

Abstract 18425: Total Aortic Volume as a Predictor of Aortic Complications in Marfan Syndrome

Background: Mortality and morbidity in Marfan syndrome, an autosomal dominant systemic connective tissue disorder, is mainly determined by aortic complications (development of aortic aneurysm and subsequent dissection). Dissection of the descending aorta usually occurs at relatively normal aortic diameters and is therefore difficult to predict. The aim of this study was to assess total aortic volume as a predictor for aortic complications in Marfan syndrome. Methods: In 96 adult MFS patients a Gadolinium enhanced 3D MRI of the aorta was performed. Total aortic volume (aortic valve - aortic bifurcation) measurement was performed with 3D vessel analysis software (3mensio vascular, 3mensio medical imaging BV, Bilthoven, the Netherlands). Aortic complications (aortic dissection and aortic surgery) during 3 years follow-up were collected from patients’ medical charts. Results: In the Marfan patients (68 % male), 22% with a history of prophylactic aortic root repair, mean age 36 ± 12 years , mean body surface area (BSA) 2.06 ± 0.24 m2) a mean aortic volume of 114 ± 25ml/m2 was calculated. Aortic complications during 3 year follow-up occurred in 17 Patients. Prophylactic aortic root replacement was performed in 13 patients (14%). Descending aortic dissection occurred in 4 patients, all after previous aortic root replacement and without aortic dilatation in the dissected parts. Mean aortic volume in patients who underwent aortic surgery during the follow-up was significantly higher as compared to the uncomplicated patients (127 ± 22 ml/m2 vs 107 ± 23 ml/m2 p = 0.006). Mean aortic volume in patients with descending aortic dissection was significantly higher as compared to the uncomplicated patients (138 ± 32 ml/m2 vs 107 ± 23 ml/m2 p = 0.012). Regression analysis revealed that total aortic volume corrected for BSA may serve as a predictor for aortic root replacement and as a predictor for descending aortic dissection (OR 1.034 95 % CI 1.008 - 1.061 p = 0,011 and OR 1.042 95 % CI 1.004 - 1. 081 p= 0.028 respectively). Conclusion: Aortic volumes may predict aortic events in Marfan syndrome.

Valve-Sparing Aortic Root Replacement in Loeys-Dietz Syndrome

Loeys-Dietz syndrome (LDS) is a recently recognized aggressive aortic disorder characterized by root aneurysm, arterial tortuosity, hypertelorism, and bifid uvula or cleft palate. The results of prophylactic root replacement using valve-sparing procedures (valve-sparing root replacement [VSRR]) in patients with LDS is not known. We reviewed all patients with clinical and genetic (transforming growth factor-β receptor mutations) evidence of LDS who underwent VSRR at our institution. Echocardiographic and clinical data were obtained from hospital and follow-up clinic records. From 2002 to 2009, 31 patients with a firm diagnosis of LDS underwent VSRR for aortic root aneurysm. Mean age was 15 years, and 24 (77%) were children. One (3%) patient had a bicuspid aortic valve. Preoperative sinus diameter was 3.9±0.8 cm (z score 7.0±2.9) and 2 (6%) had greater than 2+ aortic insufficiency. Thirty patients (97%) underwent reimplantation procedures using a Valsalva graft. There were no operative deaths. Mean follow-up was 3.6 years (range, 0 to 7 years). One patient required late repair of a pseudoaneurysm at the distal aortic anastomosis, and 1 had a conversion to a David reimplantation procedure after a Florida sleeve operation. No patient suffered thromboembolism or endocarditis, and 1 (3%) patient experienced greater than 2+ late aortic insufficiency. No patient required late aortic valve repair or replacement. Loeys-Dietz syndrome is an aggressive aortic aneurysm syndrome that can be addressed by prophylactic aortic root replacement with low operative risk. Valve-sparing procedures have encouraging early and midterm results, similar to those in Marfan syndrome, and are an attractive option for young patients.

David-operation vs. Bentall-procedure in patients with Marfans syndrome

Backround: Bentall-operation is still the standard for prophylactic aortic-root replacement in patients with Marfan-syndrome (MFS). Although valve-sparing techniques have shown favourable durability in mid-term and long-term studies, its use is still being debated in patients with MFS.

Histopathologic Findings in Ascending Aortas From Individuals With Loeys-Dietz Syndrome (LDS)

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder resulting from genetic mutations in the transforming growth factor beta receptors 1 and 2 (TGFBR1 and TGFBR2). The syndrome is characterized phenotypically by hypertelorism, bifid uvula, and/or cleft palate, and arterial tortuosity with aneurysms and dissections. LDS has a much more rapid clinical course than Marfan syndrome (MFS) and thus those diagnosed with LDS are currently being recommended for prophylactic aortic root replacement at younger ages and with smaller aortic dimensions. Aortic root tissue obtained at surgery was compared between 15 patients carrying a diagnosis of LDS, 11 patients with MFS and 11 control aortas to evaluate the range of histopathologic changes in LDS. Standard hematoxylin and eosin and Movat pentachrome stains were performed. LDS samples had increased medial collagen and a subtle but diffuse form of elastic fiber fragmentation and extracellular matrix deposition, referred to as diffuse medial degeneration. LDS samples had significantly more diffuse medial degeneration compared with MFS and control samples (P<0.05), significantly less medial degeneration of the "cystic" variety compared with MFS (P<0.01) and significantly more collagen deposition than control samples (P<0.01). Additionally, an immunohistochemical stain for pSmad2, a marker of TGFbeta activity, was significantly increased in LDS patients compared with controls (P<0.001). Overall, the histologic findings of LDS are best appreciated with special stains to evaluate fibrosis and elastic fiber fragmentation. The changes described, although not entirely specific for LDS, help differentiate this entity from other vascular diseases in the appropriate clinicopathologic setting.

Prophylactic aortic root surgery in patients with Marfan syndrome: 10 years’ experience with a protocol based on body surface area

Current guidelines recommending prophylactic aortic root replacement in Marfan syndrome are based on absolute diameters of the aortic root. However, aortic root diameter is a function of body surface area (BSA). Here, we report our experience with a protocol for prophylactic aortic root replacement based on BSA. Patients with established Marfan syndrome (Ghent criteria) and without prior aortic surgery were eligible for our study. Aortic root ratio was defined as the ratio between the observed aortic root diameter (as measured during annual echocardiography) and the maximum predicted aortic root diameter as calculated according to age and BSA. Replacement surgery was performed if dilatation of the aortic root during follow-up resulted in an aortic root ratio >/=1.3. Fifty-three patients fulfilled the entry criteria (24 men/29 women, median age at baseline 27 years, range 18-59 years). During follow-up between 1997 and 2007 (mean 4.7+/-3.2 years) four patients underwent uncomplicated aortic root replacement; two had an aortic root ratio >/=1.3 (aortic root diameters were 4.9 and 5.2 cm, respectively), one had aortic root dilatation of 0.4 cm/year and a positive family history for aortic dissection and one had an aneurysm of the ascending aorta as the primary indication. None of the patients in the whole group suffered from type A aortic dissection and there was no mortality. Although numbers are small, our protocol for prophylactic aortic root replacement in patients with Marfan syndrome based on BSA was effective in terms of preventing aortic dissection and mortality.

Actual Management of Patients with Familial Ascending Aortic Aneurysms and Type-A Aortic Dissections

There are few families with the diagnosis of ascending aortic aneurysm and acute type-A aortic dissection inherited as an autosomal-dominant disorder in the absence of a known genetic syndrome. We investigated a family with 26 members in whom ascending aortic aneurysms and acute type-A aortic dissections occurred over three generations. Examinations were performed to identify family members at specific risk. Six members presented with acute type-A aortic dissections and three relatives had ascending aortic aneurysms. Clinical examinations showed no characteristics of a known genetic syndrome. Molecular genetic analysis revealed no mutations known to cause a form of autosomal-dominant inherited aortic disease. Adequate diagnostic measures are mandatory in families with ascending aortic aneurysms or type-A aortic dissections to identify or exclude family members at risk for aortic diseases. Even in the absence of identifiable mutations causing isolated aortic aneurysms or aortic dissections, we recommend standardised examinations of all first-degree relatives of affected families. An indication for prophylactic aortic root replacement should be considered for patients at risk.

Aortic dissection complicating pregnancy following prophylactic aortic root replacement in a woman with Marfan syndrome

Prophylactic aortic root replacement is the main factor explaining the increase in median probability of survival in Marfan syndrome (MFS) patients. In women with MFS, earlier root replacement has been suggested as a strategy to facilitate safe pregnancy. However, in this case report a pregnant patient with MFS who sustained a Type B aortic dissection in her second trimester, with fatal outcome, despite having had a prophylactic aortic root replacement five months prior to conception is described.

Is there benefit of β-blocking agents in the treatment of patients with the Marfan syndrome?

Despite insufficient evidence of its beneficial effect, the prescription of h-blocking agents has become a standard practice in the prevention of aortic dilatation and dissection in patients with the Marfan syndrome. This autosomal dominant hereditary disease is a disorder of connective tissue caused by mutations or defects in the gene coding for fibrillin-1. Through intensive research over the past few years, much more information has become available about the way the modified gene product gives rise to the characteristic pathology of the disease [1]. The Marfan syndrome becomes manifested in tissues containing fibrillin, which is a large molecule constituting a major component of the microfibrils of the extracellular matrix. Insufficient production of the normal protein results both in structural tissue deficiencies and in functional abnormalities in cytokine signaling, in particular that involving transforming growth factor h. The most unfortunate, even lifethreatening, manifestation of the Marfan syndrome occurs at the aortic level. Altered biomechanical properties of the aortic wall can have dramatic consequences, the most feared of which is aortic dissection, being often lethal. Fortunately, aortic dissection is mostly preceded by a longstanding process of widening of parts of the aorta, especially of its proximal part. The degree of increase in aortic diameter is a major indicator for the risk of dissection [2]. This offers the possibility of timely replacement of the affected part by an artificial graft. In particular, the composite surgical replacement of the root and valve, as introduced by Bentall and De Bono in 1968 and subsequently modified, indicated a great improvement. Elective aortic root replacement can now be performed with very low operative mortality, and this procedure is largely responsible for the strongly increased life expectancy of these patients [3]. Nowadays, a patient diagnosed with the Marfan syndrome is immediately included in a regular follow-up program, the most important element of which is imaging of the aorta by echocardiography, CT, or preferably MRI. Once the aortic root diameter reaches a certain threshold (50–55 mm), the patient is advised to undergo prophylactic aortic root replacement. This preventive strategy is recommended in all relevant international guidelines. The recommendations further include the prescription of h-blockers to slow down the rate of dilatation of the aorta. The idea that hadrenergic receptor blockade might be useful in attenuating the aortic pathology of the Marfan syndrome is based on three known properties of h-blockers. It was believed that reduction of the heart rate, a decrease of the rate of pressure change (dp/dt) in the proximal aorta during left ventricular ejection, and a lowering of the average blood pressure should reduce the ‘‘wear and tear’’ on the aortic wall and thus slow down dilatation. Indeed, experimental evidence in humans indicates that h-blockers do improve hemodynamic parameters of the aorta, in particular aortic elasticity [4]. But do hblockers also generate clinical benefit? In their important contribution to this issue of the journal, Gersony et al. [5] conclude that there is no evidence that hblockers offer any substantial benefit. The outcome of their carefully conducted systematic review of the literature, rounded off with a meta-analysis, is that the verdict is negative. The so-called ‘‘forest’’ diagram which graphically displays the results of their analyses offers a somewhat disheartening view, considering that h-blockers have been routinely prescribed to the majority of Marfan patients for at least the past decade [6]. Most of the 6 bars representing the

Treatment of Aortic Disease in Patients With Marfan Syndrome

Marfan syndrome (MFS) is a heritable disorder of the connective tissue with a prevalence of ≈1 in 3000 to 5000 individuals. The condition is inherited in an autosomal dominant manner with complete penetrance but demonstrates variable expression with significant intra- and interfamilial variation. Approximately 25% of patients do not have a family history and represent sporadic, new mutations for the condition. The cardinal features of MFS involve the cardiovascular, ocular, and skeletal systems. The most life-threatening complication of MFS is thoracic aortic aneurysms leading to aortic dissection, rupture, or both. This article focuses on medical and surgical treatment of aortic disease in patients with MFS and addresses the treatment of aortic disease in children and pregnant women with the condition. The most common cardiovascular complication in patients with MFS is progressive aortic root enlargement initially occurring at the sinuses of Valsalva. Ascending aortic aneurysm can precipitate acute type A aortic dissection, aortic rupture, aortic regurgitation (AR), or all 3, and these complications were the primary cause of death before the advent of successful preventive therapies. Treatment of the aorta consists of regular imaging to detect and quantify progression of aortic dilation, β-adrenergic receptor antagonist therapy, and prophylactic aortic repair when the dilation reaches a sufficient size to threaten dissection or cause AR. Before the era of open-heart surgery, the majority of patients with MFS died prematurely of rupture of the aorta, with an average life expectancy of 45 years.1 The success of current medical and surgical treatment of aortic disease in MFS has substantially improved the average life expectancy, extending it up to 70 years.2,3 Cardiovascular manifestations in MFS also include valvular disease involving the mitral valve, aortic valve, or both. Mitral valve prolapse is the most prevalent valvular abnormality, affecting 35% to 100% of patients.4 Mitral …