Familial Aortic Aneurysms Research Articles

Surgical Management of Familial Aortic Disease

Pregnancy may increase the risk of aortic dissection in young women genetically predisposed in the third trimester and the peri-partum period. This disease must be managed with emergency. Later, aortic familial diseases must be screened in the children by genetic tests, because of the high risk of rapid developing dissection or aneurysm in the childhood, whose management is challenging. We report the cases of a pregnant woman operated for aortic dissection, and her son operated four years later for aneurysm of the ascending aorta, and aortic insufficiency. Children with familial aortic root aneurysm may have intervention of valve sparing and aortic replacement if the aortic regurgitation is minimal. But, long-term clinical and echocardiographic follow-up is mandatory.

Family History of Aortic Disease Has No Effect on Outcomes of Fenestrated-branched Endovascular Aortic Repair in Patients with Complex Aortic Aneurysms

Prior reports have indicated an increased risk of aneurysm-related complications after endovascular repair in patients with familial aortic aneurysms. The aim of this study was to evaluate outcomes of fenestrated-branched endovascular aortic repair (F-BEVAR) for the treatment of complex abdominal (CAAAs) and thoracoabdominal aortic aneurysms (TAAAs) in patients with familial history of aortic aneurysms or dissections (FAA). The clinical data of 506 consecutive patients (69% male; 74 ± 8 years old) enrolled in a prospective non-randomized study to investigate outcomes of F-BEVAR for the treatment of CAAAs and TAAAs between 2013 and 2022 was reviewed. Outcomes were analyzed in patients with FAA affecting a first or second-degree relative and compared with patients with sporadic aortic aneurysms (SAAs). Endpoints included differences in the distribution of aortic disease, procedural metrics, 30-day mortality, and major adverse events (MAEs), patient survival, and mid-term stent-graft-related outcomes. There were 68 patients (13%) with FAAs and 438 (87%) with SAAs. Both groups had similar cardiovascular risk factors, history of aortic dissection, and aneurysm extent. FAA patients had significantly (P < .05) longer fluoroscopy time (82 vs 71 minutes) and higher radiation dose (1782 vs 1210 mGy). Technical success was achieved in 94.1% of the FAA group and in 96.6% of SAA group (P = .51). Median follow-up was 19 months. There was no difference in 30-day mortality and MAEs, and long-term patient survival, freedom from aortic-related mortality, and freedom from secondary interventions. Patients with FAA had higher sac shrinkage >5mm as compared with patients with SAAs (P = .006). FB-EVAR was performed with high technical success, low mortality, and low incidence of MAEs regardless of the presence of FAAs. There was no difference in the distribution of aortic disease nor in stent graft-related outcomes.TableVariablesFAA (n = 68)SAA (n = 438)P valueAneurysm type (Crawford class)0.862 Extent I4 (8.0)23 (7.4) Extent II22 (44.0)103 (33.1) Extent III8 (16.0)47 (15.1) Infrarenal short neck0 (0.0)1 (0.2) Pararenal18 (26.5)125 (28.6)30-day mortality1 (1.5)4 (0.9)1.00030-day MAESpinal cord injury0.588 No62 (91.2)411 (94.3) Motor (able to ambulate)2 (2.9)7 (1.6) Non-ambulatory4 (5.9)18 (4.1)Myocardial infarction2 (2.9)10 (2.3)1.000Major stroke0 (0.0)3 (0.7)1.000Respiratory failure5 (7.4)12 (2.8)0.111Acute kidney injury0.016 No61 (89.7)396 (90.8) Creatinine >2 but no dialysis3 (4.4)34 (7.8) Temporary dialysis3 (4.4)2 (0.5) Permanent dialysis1 (1.5)4 (0.9)Long-term secondary intervention17 (25.4)96 (22.5)0.721Aneurysm sac behavior Stable17 (25.4)199 (47.2)0.001 Enlarged >5 mm3 (4.5)33 (7.8)0.471 Shrunk >5 mm47 (70.1)189 (44.8)<0.001Final sac diameter53.8 (14.9)59.3 (15.1)0.006FAA, Familial history of aortic aneurysms or dissections; MAE, major adverse event; SAA, sporadic aortic aneurysms.Data are presented as number (%) or mean (standard deviation).Boldface P values indicate statistical significance. Open table in a new tab

Endovascular therapy for patients with heritable thoracic aortic disease.

Patients with genetic or heritable aortic conditions and thoracic aortic aneurysm syndrome often develop cardiovascular abnormalities originating at the aortic root and affecting the entire thoracoabdominal aorta. Although thoracic endovascular aortic repair (TEVAR) is usually avoided in these patients, TEVAR may be worthwhile for those at high risk for surgical complications and in certain emergency circumstances. We explored indications for TEVAR in patients with suspected or confirmed genetic or heritable aortic conditions and investigated early and mid-term outcomes. Our institutional aortic surgery database was queried for patients with suspected or confirmed Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, Turner syndrome, neurofibromatosis, or familial aortic aneurysm and dissection who underwent TEVAR between February 1, 2002 and October 31, 2020. We extracted operative details and in-hospital, follow-up, and survival data. Thirty-seven patients who underwent 40 endovascular interventions met the inclusion criteria; 25 previously underwent ascending aorta or aortic root surgery, and 21 previously underwent open thoracoabdominal surgery. Postoperative complications included respiratory failure (24.3%), cardiac complications (16.2%), renal failure (13.5%), tracheostomy (8.1%), and spinal cord ischemia (paraplegia/paraparesis) (8.1%). Follow-up ranged from 1.3 to 8.5 years (median: 3.6 years), with 15 deaths overall (three early/in-hospital). Thirteen patients (35.1%) had 22 repeat interventions (open and endovascular) post-TEVAR; five had the endograft removed. Despite consensus that thoracic aneurysms in patients with genetic or heritable aortic conditions should be treated with conventional open surgery, the outcomes from our study suggest that TEVAR might be suitable in emergency settings or for patients in this population who are not candidates for open surgery, who are at high risk for reintervention, or who have a previously implanted Dacron graft. Nonetheless, lifelong surveillance is important for these patients after TEVAR to monitor for new dissection at distal or proximal landing zones, as repeat interventions are frequent.

Coronary ostial aneurysms following aortic root replacement in patients with familial aortic aneurysm are common and support the need for long-term surveillance

BackgroundFollowing the successful aortic root replacement (ARR) in patients with familial forms of aortic aneurysms (FFAA), few studies have defined the long-term outcomes of the re-implanted coronary arteries. The goal of the study was to describe late coronary complications following ARR in patients with FFAA. Methods40 patients with a genetically confirmed form of FFAA S/P ARR whom had undergone at least 1 CT scan or cardiac MRI study following ARR were identified. All studies were reviewed retrospectively and the coronary ostium were measured offline by two independent observers. ResultsThe majority of patients had Marfan Syndrome (80%), 15% had Loeys-Dietz Syndrome (TGFBR1 or TGFBR2), and 2 patients a MYLK or ACTA2 mutation. Mean age at time of ARR was 30.7 years, range 10–65. Mean length of follow-up from ARR 6.2 years, range 0.5–19. At last follow-up, 55% had developed at least 1 coronary complication. Nineteen (48%) had developed a coronary ostium aneurysm and 3 patients coronary ostium stenosis. All patients were alive at last follow-up. No patient had developed a coronary button rupture or dissection. Patients with aneurysms were more likely to have a mutation other than Marfan Syndrome (p < .05) and were more likely to have undergone emergent ARR following dissection (p = .008). Progressive coronary ostium dilation was rare. Two patients however did develop severe dilation and required button revision, both with TGFBR2 mutation. ConclusionCoronary ostium dilation is common following ARR in patients with FFAA. Progressive dilation and risk for coronary button rupture appears to be low. Patients with non-fibrillin 1 mutations, are at higher risk for severe dilation and some may require intervention. Long term surveillance in particular in patients with non-fibrillin1 forms of familial aortic aneurysm and dissection syndrome should be considered.

A novel SMAD3 mutation caused multiple aneurysms in a patient without osteoarthritis symptoms

Heterozygous mutations in the SMAD3 gene were recently described as the cause of a form of non-syndromic familial aortic thoracic aneurysm and dissection (FTAAD) transmitted as an autosomal dominant disorder and often associated with early-onset osteoarthritis. This new clinical entity, called aneurysms-osteoarthritis syndrome (AOS) or Loeys-Dietz syndrome 3 (LDS3), is characterized by aggressive arterial damages such as aneurysms, dissections and tortuosity throughout the arterial tree. We report, here, the case of a 45 year-old man presenting multiple visceral arteries and abdominal aortic aneurysms but without dissection of the thoracic aorta and without any sign of osteoarthritis. Exome-sequencing revealed a new frameshift heterozygous c.455delC (p.Pro152Hisfs*34) mutation in the SMAD3 gene. This deletion is located in the exon 3 coding for the linker region of the protein and causes a premature stop codon at positions 556–558 in the exon 4. The same mutation was found in the proband's mother and sister who had open surgery for abdominal aortic aneurysm and in one of his children who was 5 year-old and did not present aneurysm yet.

Transdifferentiation of Human Dermal Fibroblasts to Smooth Muscle-Like Cells to Study the Effect of MYH11 and ACTA2 Mutations in Aortic Aneurysms.

Mutations in genes encoding proteins of the smooth muscle cell (SMC) contractile apparatus contribute to familial aortic aneurysms. To investigate the pathogenicity of these mutations, SMC are required. We demonstrate a novel method to generate SMC-like cells from human dermal fibroblasts by transdifferentiation to study the effect of variants in genes encoding proteins of the SMC contractile apparatus (ACTA2 and MYH11) in patients with aortic aneurysms. Dermal fibroblasts from seven healthy donors and cells from seven patients with MYH11 or ACTA2 variants were transdifferentiated into SMC-like cells within a 2-week duration using 5 ng/ml TGFβ1 on a scaffold containing collagen and elastin. The induced SMC were comparable to primary human aortic SMC in mRNA expression of SMC markers which was confirmed on the protein level by immunofluorescence quantification analysis and Western blotting. In patients with MYH11 or ACTA2 variants, the effect of intronic variants on splicing was demonstrated on the mRNA level in the induced SMC, allowing classification into pathogenic or nonpathogenic variants. In conclusion, direct conversion of human dermal fibroblasts into SMC-like cells is a highly efficient method to investigate the pathogenicity of variants in proteins of the SMC contractile apparatus.

Endovascular treatment of genetically linked aortic diseases.

BackgroundThe most important structural proteins of the vascular wall are collagen and elastin. Genetically linked connective tissue diseases lead to degeneration, aneurysm formation and spontaneous dissection or rupture of arteries. The most well-known are Marfan syndrome, vascular Ehlers-Danlos syndrome (type IV), Loeys-Dietz syndrome and familial aortic aneurysms and dissections.ObjectiveThis review article addresses the current status of endovascular treatment options for important connective tissue diseases.Material and methodsEvaluation of currently available randomized studies and registry data.ResultsThe treatment of choice for patients that are mostly affected at a young age is primarily conservative or open repair. There is only limited evidence for endovascular aortic repair (EVAR) of abdominal aneurysms or thoracic endovascular aortic repair (TEVAR).ConclusionThe progression of the disease with dilatation leads to secondary endoleaks and high reintervention rates with uncertain long-term results. For this reason, there is currently consensus that EVAR and TEVAR should be limited to justified exceptional cases and emergency situations in patients with genetically linked aortic diseases.

Aortic disease in the young: pictorial review of genetic aneurysm syndromes, connective tissue disorders and familial aortic aneurysms and dissections

Purpose There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), Loeys-Dietz syndrome (LDS), familial thoracic aortic aneurysms and dissections (TAAD), bicuspid aortic valve disease (BAV), autosomal dominant polycystic kidney disease (ADPKD), Turner’s disease and neurofibromatosis. Computed tomography (CT) and magnetic resonance imaging (MRI) are the most commonly used imaging examinations to evaluate aortic diseases because of their high spatial and temporal resolutions, large fields of view and multiplanar imaging reconstruction capabilities. CT and MRI play an important role not only in the diagnosis of aortic disease but also in the preoperative assessment and follow-up after treatment. In this review, the CT and MRI appearances of various congenital aortic conditions are described and illustrated. A good working knowledge of the CT and MRI appearances of such lesions enables appropriate preoperative or interventional assessment and post procedural follow-up for detection of complications. Methods and materials N/A Results N/A Conclusion N/A

Congenital heart disease in the older adult: a scientific statement from the American Heart Association.

The population of adults with congenital heart disease (ACHD) has increased dramatically over the past few decades, with many people who are now middle-aged and some in the geriatric age range. This improved longevity is leading to increased use of the medical system for both routine and episodic care, and caregivers need to be prepared to diagnose, follow up, and treat the older adult with congenital heart disease (CHD). The predictable natural progression of CHD entities and sequelae of previous interventions must now be treated in the setting of late complications, acquired cardiac disease, multiorgan effects of lifelong processes, and the unrelenting process of aging. Despite the advances in this field, death rates in the population from 20 to >70 years of age may be twice to 7 times higher for the ACHD population than for their peers.1 This American Heart Association (AHA) scientific statement will focus on the older adult (>40 years old) with CHD. It is meant to be complementary to the 2008 American College of Cardiology (ACC)/AHA guidelines for ACHD and orient the reader to the natural history, ramifications of childhood repair, and late initial diagnosis of CHD in the older adult. This population with CHD is unique and distinct from both the pediatric and young adult populations with CHD. Much of the information we provide is from scientific research combined with clinical experience from longitudinal care. We emphasize that this is the beginning of a discussion regarding this rapidly growing population, and continued research aimed at the progression of disease and complications reviewed here is necessary to advance the field of ACHD with the scientific rigor it deserves. ACHD encompass a broad range of presentations. There are people who are diagnosed for the first time in adulthood, as well as those with prior palliative repair …

Ventricular-vascular coupling in Marfan syndrome and familial aortic aneurysm

Ventricular-vascular coupling in Marfan syndrome and familial aortic aneurysm

G.P.148: FHL1 mutations are causing familial aortic and other arterial aneurysms with scapuloperoneal myopathy

Familial aortic and other arterial aneurysms have been associated with Marfan syndrome, usually related to mutation in FBN1, and mutations in TGFBR1, TGFBR2, ACTA2, MYH11, and SMAD3. FHL1 mutations have been associated with various disorders that include reducing body myopathy (RBM), Emery–Dreifuss-like muscular dystrophy, isolated hypertrophic cardiomyopathy, and some overlapping conditions. So far no aortic diseases have been reported in these patients. Here we report a German family with a scapuloperoneal myopathy and aortic and other arterial aneurysms in two patients. Patient 1 had an aneurysm of the sinus of Valsalva and of the carotid artery, and mitral and tricuspidal valve prolapse. He received artery stenting of the carotid artery and aortic aneurysm repair. Main clinical neuromuscular features in this index patient were elevated CK levels, rigid spine, and Achilles tendon contractures. The muscle biopsy did not reveal protein aggregation. Patient 2 is also diagnosed with an aneurysm of the sinus of Valsalva and cardiac arrhythmia, but did not present any neuromuscular symptoms. Of note is that both patients presented a hallux abducto valgus deformity. We identified a novel mutation in the FHL1 gene (IVS6+1, c688+1: G>A) in four family members. The mutations were hemizygote in the two affected male patients and heterozygote in two unaffected female family members. These phenotypes provide evidence that mutations in FHL1 not only lead to neuromuscular symptoms, but also can be associated with aortic and other arterial aneurysms. This data suggest that all individuals with pathogenic FHL1 mutations should be assessed for aortic disease. Further studies are necessary to elucidate the factors responsible for the different phenotypes associated with these mutations in these patients.

Pathophysiology and Japanese clinical characteristics in Marfan syndrome.

Marfan syndrome is an autosomal dominant heritable disorder of the connective tissue, caused by mutations of the gene FBN1, which encodes fibrillin-1, a major component of the microfibrils of the extracellular matrix. Fibrillin-1 interacts with transforming growth factor-β (TGF-β), and dysregulated TGF-β signaling plays a major role in the development of connective tissue disease and familial aortic aneurysm and dissection, including Marfan syndrome. Losartan, an angiotensin II blocker, has the potential to reduce TGF-β signaling and is expected to be an additional therapeutic option. Clinical diagnosis is made using the Ghent nosology, which requires comprehensive patient assessment and has been proven to work well, but evaluation of some of the diagnostic criteria by a single physician is difficult and time-consuming. A Marfan clinic was established at the University of Tokyo Hospital in 2005, together with cardiologists, cardiac surgeons, pediatricians, orthopedists, and ophthalmologists in one place, for the purpose of speedy and accurate evaluation and diagnosis of Marfan syndrome. In this review, we discuss the recent progress in diagnosis and treatment of Marfan syndrome, and the characteristics of Japanese patients with Marfan syndrome.

Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), Loeys-Dietz syndrome (LDS), familial thoracic aortic aneurysms and dissections (TAAD), bicuspid aortic valve disease (BAV), and autosomal dominant polycystic kidney disease (ADPKD). In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research.

A Clinical Approach to a Family History of Sudden Death

Sir William Osler reportedly once said, “Varicose veins are the result of an improper selection of grandparents.” Indeed, our family history strongly influences many aspects of our cardiovascular system, with the magnitude of effect ranging from very strong for autosomal dominant genetic disorders to more subtle in the setting of complex multigenic diseases like coronary atherosclerosis and hypertension. Accordingly, the standard evaluation of any new patient who presents to a physician includes assessment of their family history. Unfortunately, the family history may sometimes be discounted as noncontributory without detailed review. This can be exacerbated by busy office schedules with declining amounts of time available for comprehensive evaluations. A few minutes saved might seem to justify the lack of focus on an aspect of history that is sometimes deemed not to be particularly useful. However, a thorough assessment of family history also may provide the key diagnostic information to determine the cause of an illness, to determine who else is at risk of disease within the family, to add useful prognostic information, and to help for family planning and reproductive decisions. A family history of sudden death should prompt consideration of a wide range of heritable cardiovascular conditions, including many monogenic disorders (Table). However, the terms used by the lay public to describe sudden death may not adequately explain the cause of death on initial consideration. For instance, the phrase “heart attack” may be used to describe sudden death of any etiology. Further questioning may help one to discern whether there was a history of heart failure, cardiomyopathy, coronary artery disease (or its risk factors), aortic aneurysm, or features of syndromic disorders that are associated with sudden death. View this table: Table. Monogenic Disorders Associated With Sudden Death A 40-year-old man presents to a physician for evaluation of palpitations. These occur briefly about once per …

Aneurysms of the Ascending Aorta

Aneurysms of the ascending aorta present a special challenge to primary care physicians, internists, and cardiac surgeons because they remain asymptomatic until they present with either dissection or rupture. This review article is based on a selective search of the literature. In the elderly, aneurysms of the ascending aorta are mainly caused by atherosclerosis. In younger patients, the most common cause is Marfan syndrome; less commonly, younger patients may have Loeys-Dietz syndrome, non-syndromic familial aortic aneurysms, or aortic valve malformations. Genetic variants predisposing to the development of sporadic aortic aneurysms have recently been identified. The risk of rupture and dissection depends on the aortic diameter: when the diameter exceeds 55 mm, surgery improves the outcome, as the risk of surgical complications is lower than the mortality due to rupture or dissection. A more accurate prognosis can be obtained by normalizing the aortic diameter to the body surface area. For patients with Marfan syndrome or a bicuspid aortic valve, the indications for surgery should be determined on an individual basis, depending on additional risk factors. Randomized treatment trials are lacking. The medical management of aneurysms of the ascending aorta consists of monitoring the size of the aneurysm, controlling blood pressure, and treating any cardiovascular risk factors. Patients with Marfan syndrome benefit from preventive treatment with beta-blockers. Advances in the pathophysiological understanding of aortic aneurysms have led to the testing of new types of treatment, e.g., with AT1 antagonists. With the aid of a risk-based treatment strategy, surgery can be properly timed to prevent dissection, which is usually lethal when it occurs. More research is needed on the pathogenesis of this condition so that better preventive treatments can be developed.

Recessively Inherited Severe Aortic Aneurysm Caused by Mutated EFEMP2

Familial aortic aneurysm (AA) is mostly inherited as an autosomal dominant disorder. However, recessively inherited AA has also been observed but in association with skin manifestations of cutis laxa, which is caused by a mutated EFEMP2 gene. In the present study, we recruited 9 patients, from 4 unrelated consanguineous families, with recessively inherited AA. The index cases, their parents, and siblings underwent clinical evaluation and cardiac imaging. In the affected subjects, the clinical presentation ranged from sweating and cyanosis at 3 months of age to incidental findings in an asymptomatic adult. The echocardiogram revealed a wide spectrum of severity of the AA, with a Z-score varying from 5 to 33. Intrafamilial variability was also evident; 2 unrelated subjects were detected at 17 and 20 years of age through family screening. The skin manifestations of cutis laxa were not found in any patient. In 1 family, genome-wide single-nucleotide polymorphism analysis detected a homozygous block, shared by 2 affected siblings, on chromosome 11 at q13. Sequence analysis of EFEMP2, located on chromosome 11 at q13, identified a novel homozygous mutation (p.E161K) in all 9 affected subjects. In this largest cohort of reported patients with a mutated EFEMP2 gene, we illustrate the phenotypic spectrum of inherited AA due to a novel EFEMP2 mutation. In conclusion, our work suggests that in families with apparently recessively inherited AA, molecular analysis of EFEMP2 gene might be warranted.

Familial aortic aneurysm and dissection due to transforming growth factor- receptor 2 mutation

This report describes the clinical course and management of a patient with Loeys-Dietz syndrome (LDS) type 2. In 2003, a 31-year-old male was diagnosed with acute aortic dissection type B; in the following six years he underwent multiple surgical and endovascular aortic procedures at different thoracic and abdominal levels secondary to progressive enlargement of both the non-dissected thoracic aorta and the false lumen distal to the left subclavian artery. LDS is characterized by arterial tortuosity and aneurysms as a result of heterozygous mutations in genes encoding transforming growth factor-β receptor 1 and 2. Further studies are required to establish the proper surgical management.

Germline TGF‐β receptor mutations and skeletal fragility: A report on two patients with Loeys–Dietz syndrome

Loeys-Dietz syndrome (LDS, OMIM # 609192) caused by heterozygous mutations in TGFBR1 and TGFBR2 has recently been described as an important cause of familial aortic aneurysms. These patients have craniofacial and skeletal features that overlap with the Marfan syndrome (MFS), and more importantly, have significant vascular fragility as is seen in MFS and Ehlers-Danlos syndrome Type IV (EDS-IV). The skeletal phenotype with respect to low bone mineral density and skeletal fragility is not clear. We present two patients with LDS with significant skeletal fragility. The first is a 17-year-old male who had talipes equinovarus, diaphragmatic and inguinal and herniae, aortic root dilatation necessitating surgical repair, craniofacial and skeletal dysmorphism consistent with LDS, and a history of numerous fragility fractures leading to significant skeletal deformity. He was found to be heterozygous for a c.923T > C transition in exon 4 of TGFBR2. The second is a 26-year-old male with submucous cleft palate, talipes equinovarus, pectus excavatum requiring surgery, inguinal hernia, and aneurysms in the ascending aorta, abdominal aorta, carotid, subclavian, vertebral and brachial arteries requiring surgical repairs. He also had craniofacial and skeletal dysmorphism consistent with LDS, multiple fractures in childhood, low bone mineral density, and was found to be heterozygous for a c.1561 T > C transition in exon 7 of TGFBR2. These case studies highlight the importance of paying close attention to fractures and bone density in patients with LDS. Osteopenia or osteoporosis may become increasingly important issues as earlier detection and treatment of the vascular complications of LDS improves life expectancy in these patients.

Aortic Root Replacement with a Composite Valved Conduit

Currently there are several operative techniques in use aroundtheworldtoaddressaorticrootpathologicproblems. These include valve-sparing aortic root replacement, stentless porcine aortic root replacement, pulmonary autograft root replacement, and composite valved graft conduits (CVG) housed with either a mechanical or in some cases a bioprosthetic valve. The CVG root replacement is the most time tested of all options and was first described by Bentall and DeBono in 1968. 1 Since then there have been many published series that have extended out beyond 20 years that demonstrate the efficacy of this approach. The indications for aortic root replacement include aneurysmal disease, aortic dissection when the primary tear occurs in the aortic root or with concomitant aortic valve disease or aneurysmal disease, and invasive aortic valve endocarditis that involves the aortic root. Most commonly aortic root replacement is performed for aneurysmal disease that stems from a degenerative process or is secondary to a genetic abnormality that predisposes to proximal aortic dilation as in Marfan syndrome, Loeys‐Dietz syndrome, Ehlers‐Danlos syndrome vascular-type (type IV), familial aortic aneurysm or dissection syndromes, and aneurysm associated with bicuspid aortic valve. Abnormal aortic root and ascending aortic dimensions have been determined based on patient age and body size. Accrual of large amounts of echocardiographic and crosssectional imaging data from normal individuals has allowed the development of regression formulas and nomograms to define abnormal aortic dilation. For example, an individual 18 to 40 years old will have an average aortic diameter at the sinus level equal to 0.97 (1.12 BSA [m 2 ]) (cm). The upper limit of normal is 2.1 cm/m 2 for the sinus segment in most adults. The aorta is pathologically dilated if its diameter exceedsthenormforagivenageandbodysurfacearea(BSA). Itisdefinedasananeurysmifitsdiameteris50%greaterthan the norm. There remains some debate as to what the indication for operative intervention should be based on maximal orthogonal diameter alone without consideration of other clinical factors like aortic valve pathologic complications. Clearly, there are cohorts of patients with aortic root and ascending aortic aneurysms that are at higher risk of an aortic catastrophe (dissection, disruption, or sudden death) than others, like patients with a bona fide connective tissue disorder or family history of aortic dissection. Moreover, surgeon experience with aortic root replacement operations varies widely. Highvolumecentershavetendedtogeneratethebestresults,

Selection for screening for familial aortic aneurysms.

The reported familial clustering of abdominal aortic aneurysm (AAA) indicates the possible rewards of family-based screening programmes with respect both to the number of asymptomatic aneurysms detected and to identifying associated genes. Ultrasonographic screening of 28 families (25 brothers and 28 sisters) was carried out together with collecting a history and a blood sample for analysis of the cholesterol level and genetic markers. Among the screened siblings six (11 per cent), all > 60 years old, had an AAA > or = 3.0 cm in diameter. A further 11 siblings (21 per cent), six of whom were < 60 years old, had a wide (2.5-2.9 cm) aorta. The presence of an aneurysmal or wide aorta was significantly associated with smoking (P = 0.027), male sex (P = 0.008) and a proband age of < 60 years (P = 0.031). Polymorphic genetic markers for type III collagen and haptoglobin were not informative in these families. These results indicate that the efficiency of screening siblings of patients with AAA could be improved by limiting it to brothers with a smoking history and/or siblings of younger patients. The familial component appears to be greatest in these younger patients.