Comparable surgical outcomes of abdominal aortic aneurysm repair in patients with and without Marfan syndrome.

OBJECTIVE: Marfan syndrome (MFS) affects the cardiovascular system. Aortic root aneurysm is a pathognomonic feature of MFS; however, the abdominal aorta is rarely affected. A consensus on surveillance for the abdominal aorta in patients with MFS has not been established. In the present study, we compared the outcomes after open surgical repair (OSR) of abdominal aortic aneurysms (AAAs) in patients with and without MFS. METHODS: We conducted a retrospective, single-center cohort study from 2003 to 2020. We reviewed and compared 28 patients with MFS and 426 patients without MFS who had undergone OSR for AAAs. The baseline characteristics, medical comorbidities, previous cardiovascular surgery, anatomic features of the AAAs, and surgical treatment outcomes were compared between the two groups. RESULTS: The patients with MFS were younger than those without MFS at the AAA diagnosis (47.2 ± 12.3 vs 70.6 ± 7.9 years; P < .001). The proportion of women was also greater for those with MFS (46.4% vs 15.7%; P < .001). The AAAs were most often located at the infrarenal aorta in both groups. However, thoracoabdominal AAAs were more often found among patients with MFS (10.7% vs 0.9%; P < .012). The proportion of symptomatic patients was lower in the MFS group (3.6% vs 21.6%; P = .022). The maximum median diameter of the AAA at surgery was smaller in the patients with MFS (52 mm vs 58 mm; P = .001). However, concomitant aortic dissection (32.1% vs 3.3%; P < .001) was more prevalent among the patients with MFS. Consequent aneurysmal changes in the iliac artery after AAA repair were more frequent in the patients with MFS (7.1% vs 0%; P = .004). No significant differences were found in 30-day or overall mortality between the patients with and without MFS during a median follow-up period of 71 months (interquartile range, 24.7-121.1 months) and 26.7 months (interquartile range, 7.4-69.5 months), respectively. CONCLUSIONS: The surgical outcomes of OSR for AAAs for patients with MFS were not significantly different from those for patients without MFS in a well-established surveillance program of MFS.

Outcomes of Thoracic Endovascular Aneurysm Repair (TEVAR) in Patients With Connective Tissue Disorders.

OBJECTIVES: Thoracic endovascular aortic repair (TEVAR) remains controversial in patients with connective tissue disorders given the concern for durability. We report on the largest series to date on outcomes of patients with thoracic aortic disease and connective tissue disorders treated with TEVAR. METHODS: The Vascular Quality Initiative registry identified 12 207 patients treated with TEVAR from January 2010 to December 2018, including 102 with Marfans, Ehlers-Danlos, or Loey-Dietz syndrome. Outcomes were analyzed per the Society for Vascular Surgery reporting standards. RESULTS: Median age was 50.6 years (interquartile range: 57.0-75.0), and 62 (60.7%) were male. Eighty-eight (86.3%) patients had Marfan, 9 (8.8%) had Ehlers-Danlos, and 5 (4.9%) had Loey-Dietz syndrome. Twenty-six (25.5%) patients were treated for degenerative aneurysmal disease and 76 (74.5%) patients for type B dissections (33 acute, 31 chronic). Most common indications for interventions in patients with type B dissection were pain (n = 41), aneurysmal degeneration (n = 16), and malperfusion (n = 8), with 3 patients who presented ruptured. There was no significant difference in perioperative complications between acute/chronic dissections and aneurysms (P = .14). Percutaneous access was utilized in 61.7% of patients, with a 2.9% rate of arterial injury requiring reintervention. Follow-up data were available for 75 (73.3%) patients at a mean follow-up of 15.6 months. Overall mortality was 5.3%. There were 30 patients with follow-up endoleak data, and 8 (26.7%) endoleaks were identified. All endoleaks were in patients treated for acute type B dissection, and all resolved after a mean of 2.1 reinterventions. Three patients treated for acute Type B Aortic Dissection (TBAD) had retrograde dissections requiring intervention. DISCUSSION: Thoracic endovascular aortic repair for patients with connective tissue disorders can be performed with low perioperative mortality, spinal cord ischemia, or Cerebrovascular Accident (CVA). On follow-up, acute type B aortic dissections represent a higher risk subgroup with increased rates of endoleak and retrograde dissection. Closer follow-up for these patients and early reintervention may be beneficial.

A 10-year study of surgical results of descending aorta aneurysm repair following chronic aortic dissection.

BACKGROUND: Patients presenting with descending aortic aneurysms developing after aortic dissection often undergo continued aortic expansion which may require operative interventions to address the risk of aortic rupture. In light of the current advances in various treatment options, including endovascular approaches, we analyzed our experience with open surgical repair (OSR) of aneurysms of the descending aorta following aortic dissection. METHODS: Patients who underwent open repair for aneurysmal changes of the descending aorta after chronic dissection were retrospectively studied. The 30-day operative mortality rate, midterm survival, and major complications were analyzed. Patients were divided into two categories; primary chronic type B aortic dissection and remnant repaired type A aortic dissection (RTAAD). RESULTS: There were 149 patients with enlargement of the descending thoracic aorta developing after aortic dissection. Of these, 49 patients had medical management, while the remaining 100 patients received OSR. These patients were included in the present analysis. The 30-day mortality and permanent paraplegia rates were 9% and 4%, respectively. The 1-, 3-, and 5-year survival rates were 83%, 80.9%, and 76.1%, respectively. The 1- and 5-year survival rates between the primary chronic type B aortic dissection and remnant RTAAD groups showed no significant between-group differences at 86.7% and 84.3%, and 80% and 71.3%, respectively (P = .289). The overall outcomes of other complications such as renal injury, bleeding reoperation, and extracorporeal membrane oxygenation support showed no significant between-group differences, including an insignificantly higher neurologic complication rate in the remnant RTAAD group. The survival rate in patients with Marfan syndrome was significantly higher than in the patients without Marfan syndrome (P = .033). CONCLUSIONS: OSR for descending aortic aneurysms developing after chronic aortic dissection showed good early and mid- to long-term outcomes, with acceptably low complication rates. OSR for descending aortic aneurysm after chronic aortic dissection associated with Marfan syndrome also showed good early and mid- to long-term outcomes.

Pathogenic FBN1 Genetic Variation and Aortic Dissection in Patients With Marfan Syndrome.

BACKGROUND: Aortic risk has not been evaluated in patients with Marfan syndrome and documented pathogenic variants in the FBN1 gene. OBJECTIVES: This study sought to describe aortic risk in a population with Marfan syndrome with pathogenic variants in the FBN1 gene as a function of aortic root diameter. METHODS: Patients carrying an FBN1 pathogenic variant who visited our reference center at least twice were included, provided they had not undergone aortic surgery or had an aortic dissection before their first visit. Aortic events (aortic surgery or aortic dissection) and deaths were evaluated during the 2 years following each patient visit. The risk was calculated as the number of events divided by the number of years of follow-up. RESULTS: A total of 954 patients were included (54% women; mean age 23 years). During follow-up (9.1 years), 142 patients underwent prophylactic aortic root surgery, 5 experienced type A aortic dissection, and 12 died (noncardiovascular causes in 3, unknown etiology in 3, post-operative in 6). When aortic root diameter was <50 mm, risk for proven type A dissection (0.4 events/1,000 patient-years) and risk for possible aortic dissection (proven aortic dissection plus death of unknown cause, 0.7 events/1,000 patients-years) remained low in this population that was treated according to guidelines. Three type A aortic dissections occurred in this population during the 8,594 years of follow-up, including 1 in a patient with a tubular aortic diameter of 50 mm, but none in patients with a family history of aortic dissection. The risk for type B aortic dissection in the same population was 0.5 events/1,000 patient-years. CONCLUSIONS: In patients with FBN1 pathogenic variants who receive beta-blocker therapy and who limit strenuous exercise, aortic risk remains low when maximal aortic diameter is <50 mm. The risk of type B aortic dissection is close to the remaining risk of type A aortic dissection in this population, which underlines the global aortic risk.

Presentation, surgical intervention, and long-term survival in patients with Marfan syndrome.

OBJECTIVE: Patients with Marfan syndrome (MFS) often present with acute catastrophic aortic events at a young age and have a shortened life span. This study examines the impact of presentation and demographics on late survival in patients with MFS. METHODS: Adults with confirmed MFS in our thoracic aortic center dataset were identified and statistical analysis performed to identify the incidence and predictors of aortic interventions and late mortality. RESULTS: We identified 301 patients with a MFS initial diagnosis at age 17 years (interquartile range, 4-30 years) with presentation into our thoracic aortic center at 21 years (interquartile range, 8-34 years). The average follow-up in our center was 10 ± 10 years. Clinical features were 41% male, 86% white race, coronary artery disease 28%, hypertension 40%, peripheral vascular disease 19%, and anti-impulse agent in 51% (ß-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, calcium channel blocker). Distribution of operative aortic pathology was isolated to the ascending aorta (70%) and descending aorta (8%). One hundred seventy-eight patients (59%) required primary aortic surgery (36% emergent). Primary procedures were cardiac (aortic valve/root) in nature in 94%. Seventy-four patients (42%) required multiple aortic procedures at a mean of 9.2 ± 6.9 years, involving the thoracoabdominal aorta in 65%, thoracic aorta in 37%, and abdominal aorta in 21%. Patients who required multiple aortic procedures were more likely (P < .05) to have coronary artery disease (50% vs 30%), and peripheral vascular disease (43% vs 18%). Multiple aortic procedures were also more likely (P < .05) in patients who developed de novo distal dissection (14% vs 0%), had prior dissection (47% vs 18%), or unknown MFS at the time of the initial procedure (27% vs 63%). Multivariable analysis identified prior dissection as an independent predictor of need for emergent surgery (odds ratio, 13.20; 95% confidence interval, 4.64-37.30; P < .05), as well as additional aortic surgery (odds ratio, 4.42; 95% confidence interval, 1.87-10.50; P < .05). Kaplan-Meier analysis showed similar 10-year survival with or without aortic interventions (82% with vs 89% without; P = .08). Late survival was decreased in patients undergoing emergent initial procedures (66% vs 89%; P < .01), as well as those undergoing multiple operations (74% vs 86%; P = .03). CONCLUSIONS: These data indicate that, in the modern era, the mode of presentation and need for multiple procedures have a detrimental impact on late survival. Additionally, the presence of acute or chronic dissection predicts the need for additional aortic procedures during follow-up.

Perinatal diagnosis and management of early-onset Marfan syndrome: case report and systematic review.

Early onset Marfan syndrome is the most severe form of Marfan syndrome diagnosed during perinatal period. Early onset Marfan syndrome is associated with high mortality rates, usually within the first 2 years of life. First, we present a case of prenatally diagnosed early onset Marfan syndrome in a dichorionic diamniotic twin pregnancy, where suspicion was raised at 35 weeks of gestation. Ultrasound and fetal magnetic resonance imaging were used to assess prenatal findings in the affected fetus. She presented right diaphragmatic eventration, elongation of humerus and femur and subluxation of the crystalline lens. She died 3 months after birth. Secondly, we present a PubMed-based review of the published articles on early onset Marfan syndrome, with pre- or postnatal suspicion or diagnosis. We found 39 articles published between 1981 and 2017, arising information on 55 cases. Including ours, early onset Marfan syndrome was prenatally diagnosed in 34.54% of the cases. In these cases, the most frequent prenatal findings were cardiomegaly, dilatation of the great vessels and mitral or tricuspid regurgitation. Mortality rate during the first 15 months after birth was 73.68%. In the postnatally diagnosed cases, the most frequent findings were arachnodactyly, dilatation of the great vessels and mitral or tricuspid regurgitation. Mortality rate was 61.11%. Overall genetic confirmation was performed in 67.27% of the cases. Prenatal diagnosis of early onset Marfan syndrome is challenging but of utmost importance, since management should take place in a tertiary care center, by a multidisciplinary team. Differential diagnosis is essential in order to perform an adequate genetic counseling.

Management of the aortic arch in patients with Loeys-Dietz syndrome.

OBJECTIVES: We sought to develop strategies for management of the aortic arch in patients with Loeys-Dietz syndrome (LDS) through a review of our clinical experience with these patients and a comparison with our experience in patients with Marfan syndrome (MFS). METHODS: We reviewed hospital and follow-up records of 79 patients with LDS and compared them with 256 patients with MFS who served as reference controls. RESULTS: In the LDS group, 16% of patients presented initially with acute aortic dissection (AAD) (67% type A, 33% type B) or developed AAD during follow-up, compared with 10% of patients with MFS (95% type A, 5% type B). There was no difference between patients with LDS or MFS in need for subsequent arch interventions after aortic root surgery (46% vs 50%, P = 1.0). Among the patients who never had AAD, the need for arch repair at initial root surgery was greater in patients with LDS (5% vs 0.4%, P = .04), as was the need for any subsequent aortic surgery (12% vs 1.3%, P = .0004). Late mortality in patients with LDS after arch repair was greater than in those patients who had no arch intervention (33% vs 6%, P = .007). CONCLUSIONS: In the absence of dissection, patients with LDS have a greater rate of arch intervention after root surgery than patients with MFS. After a dissection, arch reintervention rates are similar in the 2 groups. Arch intervention portends greater late mortality in LDS.

Incidence of cardiovascular events and risk markers in a prospective study of children diagnosed with Marfan syndrome.

BACKGROUND: Little is known about the incidence of cardiovascular events (CVEs) and their associated risk markers in children with Marfan syndrome (MFS). AIMS: To assess the incidence of CVEs and determine risk markers in a cohort diagnosed with Marfan syndrome during childhood and followed for several years. METHODS: From a French multicentre nationwide database, 462 patients with MFS diagnosed during childhood were included prospectively. Patients' files were screened for a period of 20 years (1993-2013). CVEs (e.g. death, aortic dissection, cardiac valve or aortic root surgery) were assessed during the prospective follow-up. RESULTS: Median (interquartile range) age at the end of follow-up was 17.2 (11.1-21.3) years. CVEs were reported for 35 participants (7.6%; 95% confidence interval [CI] 5.3-10.4%). First CVEs were prophylactic aortic root surgery (n=29), aortic dissection (n=4; two aged <18 years) and death (n=2). Kaplan-Meier cumulative incidence of CVEs was 5.3% (95% CI 3.3-8.7%) during childhood (aged≤18 years) and 19.4% (95% CI 13.3-27.9%) at 25years of age. The cumulative rate of CVEs was higher in case of Valsalva sinus Z-score increase of≥0.1 per year (P=0.0003), maximal Valsalva sinus diameter growth speed ≥5mm per year (P=0.03), aortic regurgitation≥2 (P=0.0005) and maximal Valsalva sinus Z-score≥3 before 16 years of age (P<0.0001). In a multivariable Cox proportional analysis, the Valsalva sinus Z-score remained significantly related to outcome. Considering aortic root evolution, aortic regurgitation, age at diagnosis and beta-blocker therapy were related to Valsalva sinus Z-score evolution during follow-up. CONCLUSIONS: CVEs in children with MFS are mainly related to prophylactic aortic root surgery. Aortic dissections are rarely observed in children. The Valsalva sinus Z-score is a strong indicator of subsequent CVEs in children with MFS. Attention to follow-up and beta-blocker observance may be warranted in high-risk children.

Thoracic Aortic, Aortic Valve, and Mitral Valve Surgery in Pediatric and Young Adult Patients With Marfan Syndrome: Characteristics and Outcomes.

Patients with Marfan syndrome (MFS) often require surgical intervention on the mitral valve (MV), aortic root or valve (AV), or thoracic aorta (TA) during childhood and adolescence. We aim to utilize a national database to evaluate outcomes in pediatric and young adult patients with MFS undergoing MV, AV, and aortic surgical procedures, and describe factors associated with increased mortality. The Pediatric Hospital Information System (PHIS) database, a multi-institutional administrative database of 48 pediatric hospitals, was queried for patients less than 25 years of age with a diagnosis of MFS (ICD-9 759.82) who underwent MV, AV, or thoracic aortic surgery between January 2004 and October 2015. We assessed comorbidities and complications, and performed univariate analysis to evaluate factors associated with inpatient mortality. Included were 321 hospital encounters in 294 patients. Fifty-one patients underwent 54 MV surgeries, 213 patients underwent 224 aortic/AV surgeries, and 43 patients underwent both MV and aortic/AV surgery in the same encounter. Postoperative complications were common for all surgeries (46.3% for MV procedures and 45.5% for aortic/AV procedures). Overall in-hospital mortality was 2.2% (3.7% for MV procedures, 1.8% for AV/aortic procedures, and 2.3% in the combined MV and aortic/AV procedure group). Aortic dissection or rupture was reported in 3.4%, with no in-hospital mortalities. Death after MV as well as after aortic/AV surgery was associated with younger age. Postoperative complications are common in pediatric and young adult patients with MFS after intervention on the MV, AV, and TA, although mortality is relatively low.

Valve-sparing aortic root replacement in children: Outcomes from 100 consecutive cases.

OBJECTIVE: Valve-sparing root replacement is an attractive alternative to composite mechanical or biologic prostheses for aortic root aneurysms in children. Data on outcomes in pediatric patients are limited. We present our institutional experience with 100 consecutive pediatric valve-sparing aortic root procedures. METHODS: All children who underwent valve-sparing root replacement at our institution from May 1997 to August 2017 were identified, and echocardiographic and clinical data were reviewed. The primary end point was mortality, and secondary end points included complications, further interventions, and subsequent valvular dysfunction. RESULTS: Median age at operation was 13.6 years (interquartile range, 9.42-15.9); 51 patients (51%) had Marfan syndrome, and 39 patients (39%) had Loeys-Dietz syndrome. Mean preoperative maximum sinus diameter was 4.4 ± 0.71 cm (z score 7.3 [5.7-9.3]). Most patients (n = 80, 80%) underwent reimplantation procedures with a Valsalva graft. Four patients (4%) underwent David I reimplantation with a straight-tube graft, 13 patients (13%) underwent a Yacoub remodeling procedure, and 3 patients (3%) underwent a Florida sleeve procedure. Perioperative valve-sparing root replacement mortality was 2% (n = 2). Six patients required late reintervention for development of pseudoaneurysms. Eight patients underwent additional aortic surgery. Average time to reoperation was 7.23 ± 4.56 years. Of the 84 patients undergoing a reimplantation procedure, 5 (5.9%) underwent late valve replacement versus 5 (33.3%) of the 15 patients who received a remodeling procedure (P = .001). CONCLUSIONS: Valve-sparing root replacement is a safe and effective option for children with aortic root aneurysms in children. The reimplantation procedure is preferred. Late aortic insufficiency and pseudoaneurysm formation remain late concerns.

Proximal aorta longitudinal strain predicts aortic root dilation rate and aortic events in Marfan syndrome.

AIMS: Life expectancy in Marfan syndrome patients has improved thanks to the early detection of aortic dilation and prophylactic aortic root surgery. Current international clinical guidelines support the use of aortic root diameter as a predictor of complications. However, other imaging markers are needed to improve risk stratification. This study aim to ascertain whether proximal aorta longitudinal and circumferential strain and distensibility assessed by cardiac magnetic resonance (CMR) predict the aortic root dilation rate and aortic events in Marfan syndrome. METHODS AND RESULTS: One hundred and seventeen Marfan patients with no previous aortic dissection, cardiac/aortic surgery, or moderate/severe aortic regurgitation were prospectively included in a multicentre protocol of clinical and imaging follow-up. At baseline, CMR was performed and proximal aorta longitudinal strain and ascending aorta circumferential strain and distensibility were obtained. During follow-up (85.7 [75.0-93.2] months), the annual growth rate of aortic root diameter was 0.62 ± 0.65 mm/year. Fifteen patients underwent elective surgical aortic root replacement and four presented aortic dissection. Once corrected for baseline clinical and demographic characteristics and aortic root diameter, proximal aorta longitudinal strain, but not circumferential strain and distensibility, was an independent predictor of the aortic root diameter growth rate (P = 0.001, P = 0.823, and P = 0.997, respectively), z-score growth rate (P = 0.013, P = 0.672, and P = 0.680, respectively), and aortic events (P = 0.023, P = 0.096, and P = 0.237, respectively). CONCLUSION: Proximal aorta longitudinal strain is independently related to the aortic root dilation rate and aortic events in addition to aortic root diameter, clinical risk factors, and demographic characteristics in Marfan syndrome patients.

[Maternal mortality among women with Marfan syndrome or vascular Ehlers-Danlos syndrome in France, 2001-2012]. / Mortalité maternelle chez les patientes atteintes de syndromes de Marfan ou d'Ehlers-Danlos vasculaire en France, 2001­2012.

OBJECTIVE: To describe maternal deaths in France associated with Marfan's syndrome or vascular Ehlers-Danlos syndrome. STUDY DESIGN: A retrospective descriptive study based on data from the national confidential enquiry into maternal deaths, in France, during 2001-2012. Characteristics of the patients, their pregnancies and details of their deaths were analysed. The specific maternal mortality ratio by Marfan's syndrome or vascular Ehlers-Danlos syndrome was estimated. RESULTS: Among 973 maternal deaths that occurred during the study period, five (0.4%) had a Marfan's syndrome (n=3) or a vascular Ehlers-Danlos syndrome (n=2), confirmed or suspected. The maternal mortality ratio due to Marfan's syndrome or vascular Ehlers-Danlos syndrome between 2001 and 2012 was 0.04/100,000 live births (IC 95% [0.011-0.2]). Three maternal deaths were caused by aortic dissections and two by other arterial ruptures. The deaths have occurred after 37 weeks of pregnancy for 4 patients, and at fifteen days of post-partum for one patient. The median age of death was 30 years. Three patients were nulliparous. Marfan's syndrome and vascular Ehlers-Danlos syndrome were not identified before the death of these five patients. CONCLUSION: Five patients with, or suspected to have, Marfan's syndrome or vascular Ehlers-Danlos syndrome were identified. Early diagnosis of these syndromes in pregnant women before life threatening events is very important, especially to refer them to appropriate care.

Aortic Surgery Outcomes of Marfan Syndrome and Ehlers-Danlos Syndrome Patients at Teaching and Nonteaching Hospitals.

BACKGROUND: Despite improvements in prevention and management, aortic aneurysm repair remains a high-risk operation for patients with Marfan syndrome (MFS) and Ehlers-Danlos syndrome (EDS). The goal of this study was to examine differences in characteristics and outcomes of patients with MFS or EDS undergoing aortic aneurysm repair at teaching versus nonteaching hospitals. METHODS: We used the National Inpatient Sample to study patients with MFS or EDS undergoing open or endovascular aortic aneurysm repair from 2000 to 2014. RESULTS: Of 3487 patients (MFS = 3375, EDS = 112), 2974 (85%) had repair at a teaching hospital. Patients who underwent repair at a teaching hospital were slightly younger than those who underwent repair at a nonteaching hospital (38 vs. 43 years, P < 0.01) but otherwise were similar in gender (29% vs. 28% female), race (70% vs. 78% white), and connective tissue disorder diagnosis (97% vs. 97% MFS, all P ≥ 0.1). There were no differences in anatomy (17% vs. 19% abdominal, 67% vs. 66% thoracic, and 15% vs. 15% thoracoabdominal, all P ≥ 0.1) or type of repair (5% vs. 5% endovascular), but patients at nonteaching hospitals were more likely to have a dissection (49% vs. 38%, P = 0.02). There was no difference in perioperative mortality (4% vs. 6%, P = 0.5) or length of stay (median 8 days vs. 7 days, P = 0.3) between teaching and nonteaching hospitals. There was also no difference in hemorrhagic (47% vs. 43%), pulmonary (9% vs. 16%), renal (12% vs. 14%), or neurologic (5% vs. 6%) complications between teaching and nonteaching hospitals, respectively (all P ≥ 0.05). In analysis stratified by anatomic extent of repair, there was a lower prevalence of pulmonary complications in thoracic aorta repairs at teaching hospitals (8.1% vs. 18.4%, P = 0.01) but a higher prevalence of hemorrhage in abdominal aortic repairs at teaching hospitals (45.6% vs. 20.6%, P = 0.04) as compared with nonteaching hospitals. CONCLUSIONS: Patients with MFS and EDS who undergo aortic aneurysm repair have their operations predominantly at teaching hospitals, but those patients who undergo repair at nonteaching hospitals do not have worse mortality or morbidity despite a higher incidence of dissection.

Survival, causes of death, and cardiovascular events in patients with Marfan syndrome.

BACKGROUND: To explore survival, causes of death, and the prevalence of cardiovascular events in a Norwegian Marfan syndrome (MFS) cohort. MFS is a heritable connective tissue disorder associated with reduced life expectancy-primarily due to aortic pathology. METHODS: A follow-up study of 84 MFS adults, initially investigated in 2003-2004. In 2014-2015, 16 were deceased, 47 of 68 survivors consented to new clinical investigations. Analyses of events were performed for 47 survivors and 16 deceased at follow-up. Standardized mortality ratios (SMR), using the mortality rate of the Norwegian population as reference, were calculated for all 84 and calculated for men and women separately. Causes of death and information on cardiovascular events were retrieved from death certificates and medical records. RESULTS: Standardized mortality ratios (95% confidence interval): for the whole cohort: 5.24 (3.00-8.51); for men: 8.20 (3.54-16.16); for women: 3.85 (1.66-7.58). Cardiovascular causes were found in 11 of 16 deceased, eight of these related to aortic pathology. Cancer was the cause of death in three patients. At follow-up, 51% had new cardiovascular events; 59% had undergone aortic surgery. Men experienced aortic events at younger age than women. 32% of the survivors were not followed-up as recommended. CONCLUSION: Life expectancy is reduced in this MFS cohort compared to the Norwegian population. Cardiovascular complications develop throughout life, particularly aortic pathology, the major cause of death in MFS. Death and aortic pathology seem to occur earlier in men. There is a need to improve follow-up according to guidelines.

Losartan Versus Atenolol for Prevention of Aortic Dilation in Patients With Marfan Syndrome.

BACKGROUND: Beta-blockers are the standard treatment in Marfan syndrome (MFS). Recent clinical trials with limited follow-up yielded conflicting results on losartan's effectiveness in MFS. OBJECTIVES: The present study aimed to evaluate the benefit of losartan compared with atenolol for the prevention of aortic dilation and complications in Marfan patients over a longer observation period (>5 years). METHODS: A total of 128 patients included in the previous LOAT (LOsartan vs ATenolol) clinical trial (64 in the atenolol and 64 in the losartan group) were followed up for an open-label extension of the study, with the initial treatment maintained. RESULTS: Mean clinical follow-up was 6.7 ± 1.5 years. A total of 9 events (14.1%) occurred in the losartan group and 12 (18.8%) in the atenolol group. Survival analysis showed no differences in the combined endpoint of need for aortic surgery, aortic dissection, or death (p = 0.462). Aortic root diameter increased with no differences between groups: 0.4 mm/year (95% confidence interval: 0.2 to 0.5) in the losartan and 0.4 mm/year (95% confidence interval: 0.3 to 0.6) in the atenolol group. In the subgroup analyses, no significant differences were observed considering age, baseline aortic root diameter, or type of dominant negative versus haploinsufficient FBN1 mutation. CONCLUSIONS: Long-term outcome of Marfan syndrome patients randomly assigned to losartan or atenolol showed no differences in aortic dilation rate or presence of clinical events between treatment groups. Therefore, losartan might be a useful, low-risk alternative to beta-blockers in the long-term management of these patients.

Causes of Mortality in the Marfan Syndrome(from a Nationwide Register Study).

The Marfan syndrome (MFS) is strongly associated with aortic disease causing a high prevalence of prophylactic aortic surgery, aortic dissection, and sudden death. The aim of the present study was to evaluate mortality in a nationwide Danish MFS population diagnosed by the Ghent II criteria. In a register-based setting, we identified all Danish patients with MFS (n = 412, men n = 215) by assessment of their medical records. We established a gender and age matched control cohort based on 41,000 control patients (men n = 21,500). MFS cases risk time was 6,669 patient years. We applied Cox regression using each case and his/her control as one stratum, adjusting for age and calendar time. We found a significantly decreased lifespan of 50years compared with 60years among controls. The mortality hazard ratio among MFS compared with controls was significantly increased to3.6 (CI 2.8-4.7, p < 0.001); men 4.0 (CI 2.8-5.7, p < 0.001); women 3.2 (CI 2.1-4.8,p < 0.001). Aorta disease represented the main reason for the overall increased mortality with a hazard ratio of 194.6 (CI 67.4-561.7, p < 0.0001); men 208.7 (CI 53.8-809.1, p < 0.001); women 173.4 (CI 31.5-954.5, p < 0.001). In addition, an unexplained mortality due to respiratory illness was not attributed to pneumothorax. Excluding cardiovascular and respiratory causes of death, we found no indication that MFS is associated with increased mortality for other reasons.

A systemic review and meta-analysis: long-term results of the Bentall versus the David procedure in patients with Marfan syndrome.

This systemic review of the literature and meta-analysis aimed to evaluate the current state of the evidence for and against reimplantation of the aortic valve (RAV) versus the composite valve graft (CVG) intervention in patients with Marfan syndrome. Random effects meta-regression was performed across the study arms with logit-transformed proportions of in-hospital deaths as an outcome measure when possible. Results are presented as odds ratios with 95% confidence intervals (CIs) and P-values. Other outcomes are summarized with medians, interquartile ranges (IQR) and ranges and the numbers of patients at risk. Twenty retrospective studies that included a combined 2156 patients with long-term follow-up were identified for analysis after a literature search. The in-hospital mortality rate favoured the RAV procedure with an odds ratio of 0.23 [95% CI 0.09-0.55, P = 0.001]. The survival rate at mid-term for the RAV cohort was 96.7% (CI 94.2-98.5) vs. 86.4% (CI 82.8-89.6) for the CVG group and 93.1% (CI 66.4-100) for the RAV group vs. 82.6% (CI 74.9-89.2) for the CVG group for the long term. Freedom from valve-related reintervention (median percentages) for the long term was 97.6% (CI 90.3-100%) for the RAV procedure and 88.6% (CI 79.1-95.5) for a CVG. This systematic review of the literature stresses the advantages of the RAV procedure in patients with Marfan syndrome in regard to long- and short-term results as the treatment of choice in aortic root surgery. The RAV procedure reduces in-hospital as well as long-term deaths and protects against aortic valve reintervention.