Inherited aortopathy2022
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Inherited aortopathy can cause complications like aortic dissection and repeated surgeries. This document discusses inherited aortopathies associated with congenital heart defects. Primary aortic dilatation is mainly associated with coarctation of the aorta, bicuspid aortic valve, and conotruncal abnormalities. Secondary dilatation can occur after congenital heart surgery when non-aortic tissue is used. The most serious complication is aortic dissection. Guidelines exist for investigating and treating this life-threatening event, with consideration of underlying hereditary disorders.
Inherited aortopathy2022
- 1. Inherited Aortopathy Dr Ihab Suliman March 2022
- 2. Complications • Aortic dissection. • Repeated Surgeries • Concomitant diseases
- 4. • In patients born with congenital heart disease, dilatation of the aorta is a frequent feature at presentation and during follow-up after surgical intervention. • This review provides an overview of the pathologies associated with aortopathy, and discusses the current knowledge on pathophysiology, evolution, and treatment guidelines of the aortic disease associated with congenital heart defects.
- 5. • Primary aortic dilatation is mainly associated with coarctation of the aorta (CoA), bicuspid aortic valve (BAV), and conotruncal abnormalities such as tetralogy of Fallot (TOF), pulmonary atresia with ventricular septal defect (PA/VSD), or truncus arteriosus. It can be a key feature in genetic syndromes with connective tissue disorders, such as Marfan, Loeys-Dietz, vascular Ehlers-Danlos, aneurysm-osteoarthritis, and Turner syndrome.
- 6. • Secondary dilatation of the aortic root and to a lesser extent of the ascending aorta is seen after congenital cardiac surgery, when the original aortic root is replaced by a pulmonary autograft, as in the Ross operation, or modified as in the arterial switch operation (ASO) or systemic outflow tract reconstruction in single ventricle (SV) patients. In these situations the neo-aortic root consists mainly of pulmonary arterial root tissue introduced in the high-pressure left-sided system, often leading to dilatation in a time- dependent fashion.
- 7. MORPHOGENESIS OF THE AORTIC AND PULMONARY ROOT • The aortic and pulmonary trunks originate from the remodeling of the pharyngeal arch arteries during the early embryonic development. The original six symmetrical arteries, attached to the dorsal aorta, give rise to the ascending aorta (partly derived from the left fourth artery), and pulmonary trunk (derived from the left sixth artery), with two branch pulmonary arteries attached. Neural crest cells migrate to the caudal pharyngeal arches and into the common outflow truncus of the primitive heart tube, participating in distal septation of the common outflow tract into two independent separate extra-pericardial vessels.
- 9. Syndromic aortopathies • This term includes discuss • Marfan syndrome (MFS); • Turner syndrome (TS); • Loeys Dietz syndrome (LDS); • Ehlers-Danlos, particularly type IV (vascular subtype); • and arterial tortuosity syndrome (ATS).
- 11. • Most of these conditions are characterised by autosomal dominant inheritance. Turner syndrome is due to sex chromosome aneuploidy with the loss of one of the X chromosomes (45,X). ATS is a rare autosomal recessive condition.
- 12. Most Serious complication Aortic dissection • The most serious complication of an aortopathy is an aortic dissection. Aortic dissection due to an underlying heritable disorder (whether syndromic or non-syndromic) presents in the same way as aortic dissection in the general community. Guidelines are available regarding investigation, diagnosis and treatment of this potentially life- threatening complication .Consideration of an underlying heritable disorder should be given particularly in the setting of occurrence at a young age .
- 13. Epidemiology MFS https://marfan.org/ • First described in 1896; named in 1902. • Common inherited connective tissue disorder • Incidence: 1 in 3000-5000; approximately 200,000 Americans affected • M = F; men with shorter life expectancy • Races affected equally
- 14. Aortic Dissection • Marfan syndrome (Present in 5-10% of ascending aortic dissections, .02% of adults) • Aortic dilatation • Bicuspid aortic valve, coarctation • Turner, Ehlers-Danlos (type IV), Noonan syndrome • Family history of… Marfan syndrome, aortic dissection, aortic disease • Hypertension (Present in 70-90% of dissections, but 20-40% of adults)
- 15. MFS CARDIOVASCULAR SYSTEM MAJOR CRITERIA • dilation of ascending aorta • aortic dissection MINOR CRITERIA • mitral valve prolapse • dilation of a main pulmonary artery • premature mitral anular calcification (<40yrs.) • descending thoracic or abdominal aortic aneurysm (< 50 yrs.) Cardiovascular involvement: one minor criterion
- 16. OCULAR SYSTEM MAJOR CRITERION • Ectopia lentis
- 17. SKELETAL SYSTEM MAJOR CRITERIA Presence of at least four of the following: • pectus carinatum • pectus excavatum requiring surgery • reduced upper to lower segment ratio or arm span to height ratio > 1.05 • wrist and thumb signs • scoliosis > 20° or spondylolisthesis • reduced extension at the elbows (<170°) • medial displacement of the medial malleolus causing pes planus • protusio acetabulae of any degree
- 20. DIAGNOSIS Clinical Evaluation 1. Complete physical examination, including a careful musculoskeletal and skin examination 2. Detailed medical and family history 3. Electrocardiogram (EKG) and echocardiogram, looking for cardiovascualr involvement 4. Eye examination by an ophthalmologist, who dilates the pupil and uses a slit lamp to assess for lens dislocation This series of steps is important, not only in determining the diagnosis, but also in detecting problems that require immediate attention or long-term management.
- 21. • The major criteria for diagnosis of Marfan syndrome are ectopia lentis, aortic root dilation/dissection, dural ectasia, or a combination of more than 4 out of 8 major skeletal features.
- 22. Genetics • Autosomal dominant; variable expression • ~25% spontaneous mutations • Genes involved in Marfan Syndrome phenotype: – Fibrillin-1 (MFS) • Microfibril glycoprotein in both elastic and non elastic tissues • > 97 different mutations – TGFBR (MFS type II or Loeys-Dietz) • Works through apoptosis and cell cycle regulation; prevents proper incorporation of fibrillin into tissue • Also with triad: hypertelorism, bifid uvula or cleft palate, generalized arterial tortuosity • Other gene mutations may lead to similar phenotypes
- 23. Abraham Lincoln
- 24. Diagnosis • Clinical diagnosis: the Ghent criteria – physical exam: 6 organ systems involved – family history – genetic testing • If (+) family history, additionally you need: – Involvement of 2 organ systems including 1 major criterion • If (–) family history, additionally you need: – Major criterion from 2 systems and involvement of a 3rd system
- 25. Clinical Features • HEENT: – Eye: superior lens dislocation (ectopia lentis) – Oropharynx: high palate and crowded dentition • Cardiac: – Mitral valve prolapse – Aortic root dilation • Pulmonary: Spontaneous pneumothorax • Neurologic: Dural ectasia • Skin: Stretch marks
- 26. Clinical Features • Musculoskeletal: – Tall stature (dolichostenomelia) – Long digits (arachnodactyly) – Thumb sign (distal phalanx protrudes beyond border of clenched fist) – Wrist sign (thumb and fifth digit overlap when around the wrist) – Sternal deformity (prominent pectus) – Scoliosis > 20 degrees – Joint hypermobility – Arm span exceeding height (ratio >1.05) – Reduced elbow extension (<170 degrees) – Medial displacement of medial malleolus
- 28. Cardiovascular Complications • Most common cause of M&M (~80%) • Aortic root disease aneurysms, AR, dissection – In 50% children – In up to 80% of adults – May lead to neurovascular complications – AR murmur: decrescendo, diastolic • Mitral valve prolapse (minor criterion) – In 60-80% patients; most common valve disorder – Worsens with time, complicated by rupture – MVP murmur: ejection click, holosystolic • Arrhythmias
- 29. Management: screening/counseling • Annual echocardiogram • Annual ophtho exam and orthopedic involvement as needed • Counseling regarding physical activities • Genetic counseling
- 30. Management: medications Beta blockade Standard of care for adult patients (no data on children) Based on studies of propranolol versus placebo Slower rate of aortic dilatation with beta blockade Survival at 10 yrs not significantly improved Calcium channel blockers? ARBs Recent animal study models of FBN1 mutants demonstrated decreased rate of aortic dilatation Mechanism is via TGFBR One randomized trial of 17 patients is complete: larger study is now ongoing
- 31. Management: surgical intervention • Better survival with elective repair • Variable recommendations for aortic root diameter at which intervention warranted – ACC/AHA: diameter > 5.0 cm – ESC: diameter > 4.5 cm – Rate of increase > 0.5 cm/year • Earlier intervention indicated in women desiring pregnancy • Annual imaging post-op still necessary
- 32. Similar phenotypes • Congenital contractual arachnodactyly: FBN2 • MASS (Mitral valve prolapse, aortic dilation, skin and skeletal abnormalities): FBN1 • Joint hypermobility syndrome • Ehlers-Danlos: mutation of type V collagen • Stickler syndrome: mutation of type II and XI collagen
- 33. INTRODUCTION Marfan syndrome is a multisystemic connective tissue disorder that affects both sexes equally and is characterized by skeletal, cardiovascular, and ocular abnormalities. Its prevalence has been estimated at two to three persons per 10,000 .
- 34. Case 1 28years old woman. Admitted for acute-onset tearing central chest pain that radiates to the back . CT angiography showed: Stanford type A dissection involving the ascending thoracic and the descending aorta Brachiocephalic artery dissection Right renal artery supplied by the false lumen with acute renal infarction
- 35. a dissection flap in the right brachiocephalic artery Descending aorta dissection
- 36. Ct also revealed • A severe scoliosis . • A chest wall deformity
- 37. Case 2 A 32 years old man Complaining of central chest pain and intermittent episodes of excruciating back pain confined to the sacral area . CT showed an annulo aortic ectasia with aortic aneurysms.
- 38. It also showed a dural ectasia scoliosis
- 39. Cardiovascular Manifestations 3 . Pulmonary Artery Dilatation • Dilatation of the main pulmonary artery is one of the established criteria for the diagnosis of Marfan syndrome. Like dilatation of the ascending aorta, it occurs predominantly in the root. • The upper limits of a normal main pulmonary artery diameter at the root and at the level of bifurcation, were 34.8 mm and 28.0 mm, respectively
- 40. Musculoskeletal Manifestations 1. Scoliosis • Scoliosis is a frequent and potentially severe manifestation of Marfan syndrome. It occurs in approximately 62% of patients. • Scoliosis in Marfan syndrome is more severe, rigid, and progressive, requiring surgical correction. • When it occurs in combination with straight back syndrome, kyphosis, or a chest wall deformity, it may contribute to cardiopulmonary compromise and restriction of lung volume
- 41. Musculoskeletal Manifestations • Measurement of the severity of a scoliotic curve has practical applications and the Lippman-Cobb method is widely used to measure the degree of scoliotic curvature. • CT and MR imaging are helpful to evaluate the bone structure, associated abnormalities of the spinal cord, and the nerve roots before treatment planning.
- 42. Musculoskeletal Manifestations 2 . Chest Wall Deformity • Approximately 66% of patients with Marfan syndrome have either pectus excavatum or pectus carinatum produced by longitudinal overgrowth of the ribs. • The severity of pectus excavatum is determined according to the pectus index calculated on the basis of measurements on CT images.
- 43. Musculoskeletal Manifestations 3 . Acetabular Protrusion • Acetabular protrusion is a deformity of the hip joint and is distinguished by the invasion of the acetabulum and femoral head into the pelvic cavity. • Radiographic findings, including an increased center- edge angle of Wiberg and an obscured teardrop sign, allow the diagnosis.
- 44. Dural Ectasia and Associated Central Nervous System Manifestations • Dural ectasia, which has been observed in 56% – 65% of patients with Marfan syndrome, is a ballooning or significant widening of the dural sac or neural root sleeves. • It is sometimes accompanied by bone erosion, meningoceles, and arachnoid cysts.
- 45. • Most occurrences of dural ectasia in Marfan syndrome affect the lumbosacral spine. • Dural ectasia is depicted on radiographs as a widening of the interpediculate distance. • Vertebral body scalloping occurs with a high prevalence in transition vertebrae.
- 46. Take home points • Marfan Syndrome is relatively common • If you have a patient < 40 with evidence of aortic root changes, think MFS • No cure, so cardiovascular management is key – Annual echo – Beta blockade – Counseling on physical activity
- 47. Coarctation of the aorta • CoA accounts for 5-8% of CHD.Isolated forms occur in less than half of the patients, CoA is often found in combination with BAV and mitral valve anomalies. It is usually sporadic, but genetic influences can play a role: There is a male predominance of 1,5-1,7/1, and 10- 15% of Turner syndrome patients have aortic CoA.
- 48. Bicuspid aortic valve • The BAV is the most frequent congenital cardiac malformation, with a prevalence of 1-2% in the general population. Concomitant aortic dilatation is seen in 80% of patients. • Three valve morphologies have been identified: • Type I (the most prevalent, 69-85%) has a fusion of right and left coronary cusps, • type II is fusion of right and non-coronary cusps, and • type III (the least prevalent) shows fusion of the left and non-coronary cusp. The concomitant aortic dilatation can be confined to the ascending aorta, the aortic root, or extend from the aortic annulus up to the proximal aortic arch.
- 49. • The lifetime risk of aortic dissection in patients with BAV has been reported to be 9 times higher than that of the general population.
- 50. • The BAV inheritance pattern is autosomal dominant with incomplete penetrance of 9 to 30%. The male predominance of 3/1 and the association with Turner syndrome suggest an X-linked etiology. Mutations in the ACTA2 and NOTCH1 genes have been found in some BAV patients, but not the FBN1 gene associated with Marfan syndrome.
- 51. • The strong association of BAV with CoA may indicate that BAV disease involves the ascending aorta and aortic arch extending to the ligamentum arteriosum The fact that the pulmonary trunk in BAV patients shows histological changes similar to those seen in the ascending aorta, points to a development spectrum involving that part of the great vessels that is derived from neural crest cells. •
- 52. Schematic diagram of the anatomic boundaries of BAV disease. The structures involved in BAV disease (in pink) include the aortic valve, aortic annulus, sinuses of Valsalva, sinotubular junction, ascending aorta, pulmonary trunk and coronary ostia. Adapted from Tadros et al. (ref. )
- 53. • Conotruncal anomalies: Tetralogy of Fallot and pulmonary atresia/ventricular septal defect
- 54. TOF • TOF is the most common form of cyanotic CHD and accounts for 10% of all congenital heart defects. Dilatation of the proximal aorta is a common feature in patients with unrepaired TOF and PA/VSD, which can already be observed at fetal echocardiography. The aorta in TOF is dilated mainly at the root, tapering down towards the ascending aorta; the aortic arch is usually of normal size.
- 55. • Corrective surgery has dramatically improved long-term prognosis, with nearly 90% of patients now surviving well into adulthood.However, persistent aortic root dilatation is increasingly reported in adult patients, years after corrective surgery. Single case reports of progressive aortic dilatation long after repair of TOF began appearing in the early 1970s. • .
- 56. • In 1982 Capelli and Somerville mentioned persistence of a large aortic root, but considered it an acquired feature due to long- standing volume overload by years of aortopulmonary shunts before complete repair, and suggested that earlier repair in the first decade of life might prevent this complication
- 57. Secondary aortic dilatation after repair of CHD • In this section we will consider the occurrence of dilatation of the aortic root, and to a lesser extent of the ascending aorta, after congenital cardiac surgery, by which the original aortic root is replaced by a pulmonary autograft, as in the Ross operation, or modified as in the ASO or systemic outflow tract reconstruction in SV patients. In these situations the neo-aortic root consists mainly of pulmonary arterial root tissue introduced in the high-pressure left-sided system,
- 58. After Ross procedure • Since the introduction by Sir Donald Ross in 1967 of the Ross procedure, comprising aortic replacement by the pulmonary autograft, this operation has gained widespread applicability both in children and adults with congenital aortic valve disease.Technically, the pulmonary autograft can be implanted as a full root replacement, or as a subcoronary replacement, inserting the pulmonary autograft as an inclusion cylinder in the existing aortic root. The right ventricular outflow tract reconstruction is mostly performed with a pulmonary homograft or biological xenograft root.
- 59. After arterial switch operation ASO • Over the past two decades, the ASO has become the procedure of choice for repair of transposition of the great arteries in neonates and young infants.The ASO leads to anatomic correction, in contrast to atrial switch operation, and thus avoids the long-term complications of systemic atrioventricular valve regurgitation and ventricular failure.
- 60. Single ventricle situations • Since the introduction of staged procedures for patients with SV physiology two decades ago, an increasing number of survivors with a Fontan circulation grow into adolescence and adulthood. • When the native aortic valve functions as the only outlet valve, and no surgery to the original aortic root has been performed during staging, the chances of this valve deteriorating over time are small, as the architecture and wall characteristics are apt to sustain systemic pressures. However, when volume loading persists during a considerable period of time, and the Fontan completion is postponed at an older age, or when the aortic valve is bicuspid, the aortic root and ascending aorta may dilate over time and become aneurismal.
- 61. Surgery to the ascending aorta in BAV patients is mandated (Class IIa, level C): • for an ascending aorta of >50 mm, when the patient has a family history of dissection, or the size progression is >5 mm/year • for an ascending aorta of >55 mm, when there are no risk factors • for an ascending aorta of >45 mm, when surgery for the valve is obligatory; replacement of the aortic sinuses needs to be individualized
- 62. Guidelines for follow-up and treatment • Guidelines for the follow-up and surgical treatment of adult patients with valvular heart and thoracic aortic disease are well established, and regularly updated.[In these guidelines, only BAV with thoracic aorta dilatation receives special attention. All guidelines are based on diameters; aortic size index is never used up to now. • Regarding follow-up, all patients with an aortic diameter of >40 mm should be follow-up regularly. When the diameter is >45 mm, and patients have a family history of dissection or show rapid progression, yearly imaging is mandated.
- 63. In contrast, nearly no guidelines exist for aortopathy in CHD.In the ESC guidelines for grown-up CHD, only the following are mentioned • surgical treatment for ascending aortic dilatation in CoA may be considered when the diameter is >55 mm (>27.5 mm/m2) or if rapid progression • aortic surgery should be considered after ASO when the neo-aortic root is >55 mm providing adult stature (Class IIa/level C)
- 65. • In the absence of guidelines for the other pathologies previously discussed, a pragmatic attitude is probably appropriate: As no case reports have appeared about ruptured aortas <55 mm in adult sized patients, this diameter should be used as a cut-off. A diameter of >60 mm is considered the hinge point for the ascending aorta, above which the chance for rupture increases exponentially.In small children, rapid progression in size may urge faster intervention. • Medical therapy • Co-existent arterial hypertension in patients with CHD must be effectively treated, as hypertension has been shown to accelerate the aortic dilatation.
- 66. All are chest x ray findings in thoracic aortic aneurysm except • A. Widening of the mediastinal shadow • B. Displacement or compression of the trachea • C. Displacement or compression of left main stem bronchus • D. Displacement or compression of right main stem bronchus
- 67. • D. Displacement or compression of right main stem bronchus
- 70. • C
- 72. • A
- 73. • Thank you
Editor's Notes
- #23: Fibrillin-1 homologous to TGF binding protein Transforming growth factor beta receptors 1 and 2: increased expression is associated with progression of various malignancies
- #26: Dural ectasia: enlargement of dural sac – seen in 60-80%
- #29: Untreated Marfan’s is a/w dissection: usually type 1 or type A. Often, there is family h/o dissection as well. In patients under age of 40, approx 50% of those cases are related to Marfan’s dz (also in differential is cocaine)
- #32: Studies out of Hopkins compared elective versus urgent versus emergent repair and found mortality to be 1.5%, 2.6% and 11.7%. Variable recommendations, but thus far don’t take into account patient’s body size; should women have smaller diameters at time of repair. Some studies starting to look at diameter as a standard deviation from population mean.