RESUMO
A young woman with Turner syndrome was found to have a large coronary aneurysm in the left anterior descending coronary artery upon CT angiogram screening for aortic pathology.
Assuntos
Aneurisma Coronário , Síndrome de Turner , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Vasos Coronários , Feminino , Humanos , Síndrome de Turner/complicações , Síndrome de Turner/diagnósticoRESUMO
Aneurysms-osteoarthritis syndrome (AOS) is characterized by arterial aneurysms and dissection in combination with early-onset osteoarthritis, which can impact quality of life. We describe the subjective quality of life and investigate anxiety and depression in 28 AOS patients aged 15-73 years. Three questionnaires were used: 36-Item Short Form Survey (SF-36), hospital anxiety and depression scale (HADS) and Rotterdam disease specific questionnaire. Results of the SF-36 and HADS were compared to a reference Dutch cohort and the SF-36 questionnaire also to patients with Marfan syndrome. Compared to the general population, AOS patients scored significantly lower on the following SF-36 domains: physical functioning, vitality, social functioning, bodily pain, and general health. Physical functioning was also lower than in Marfan patients. Patients with AOS scored higher on the HADS depression scale, while anxiety did not show a significant difference compared to the general population. No difference in SF-36 and HADS domain scores were found between patient with and without orthopaedic symptoms and patients with or without previous aortic surgery. Additionally, we found that patients' worries for their future and heredity of their disease are important factors for anxiety, which should be addressed in clinical practice.
Assuntos
Ansiedade/psicologia , Aneurisma Aórtico/psicologia , Dissecção Aórtica/psicologia , Depressão/psicologia , Síndrome de Marfan/psicologia , Osteoartrite/psicologia , Dor/psicologia , Adolescente , Adulto , Idoso , Dissecção Aórtica/genética , Dissecção Aórtica/fisiopatologia , Ansiedade/genética , Ansiedade/fisiopatologia , Aneurisma Aórtico/genética , Aneurisma Aórtico/fisiopatologia , Estudos de Casos e Controles , Depressão/genética , Depressão/fisiopatologia , Feminino , Expressão Gênica , Heterozigoto , Humanos , Masculino , Síndrome de Marfan/genética , Síndrome de Marfan/fisiopatologia , Pessoa de Meia-Idade , Mutação , Osteoartrite/genética , Osteoartrite/fisiopatologia , Dor/genética , Dor/fisiopatologia , Qualidade de Vida/psicologia , Proteína Smad3/genética , Inquéritos e Questionários , SíndromeRESUMO
The Loeys-Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor-ß (TGF-ß) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF-ß signaling. More recently, TGF-ß ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF-ß pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF-ß signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database.
Assuntos
Estudos de Associação Genética , Síndrome de Loeys-Dietz/genética , Mutação/genética , Proteína Smad2/genética , Proteína Smad3/genética , Fator de Crescimento Transformador beta2/genética , Fator de Crescimento Transformador beta3/genética , Animais , Modelos Animais de Doenças , Humanos , Síndrome de Loeys-Dietz/diagnóstico , Camundongos , Transdução de Sinais/genéticaRESUMO
BACKGROUND: Discrete subaortic stenosis is notable for its unpredictable hemodynamic progression in childhood and high reoperation rate; however, data about adulthood are scarce. METHODS AND RESULTS: Adult patients who previously underwent surgery for discrete subaortic stenosis were included in this retrospective multicenter cohort study. Mixed-effects and joint models were used to assess the postoperative progression of discrete subaortic stenosis and aortic regurgitation, as well as reoperation. A total of 313 patients at 4 centers were included (age at baseline, 20.2 years [25th-75th percentile, 18.4-31.0 years]; 52% male). Median follow-up duration was 12.9 years (25th-75th percentile, 6.2-20.1 years), yielding 5617 patient-years. The peak instantaneous left ventricular outflow tract gradient decreased from 75.7±28.0 mm Hg preoperatively to 15.1±14.1 mm Hg postoperatively (P<0.001) and thereafter increased over time at a rate of 1.31±0.16 mm Hg/y (P=0.001). Mild aortic regurgitation was present in 68% but generally did not progress over time (P=0.76). A preoperative left ventricular outflow tract gradient ≥80 mm Hg was a predictor for progression to moderate aortic regurgitation postoperatively. Eighty patients required at least 1 reoperation (1.8% per patient-year). Predictors for reoperation included female sex (hazard ratio, 1.53; 95% confidence interval, 1.02-2.30) and left ventricular outflow tract gradient progression (hazard ratio, 1.45; 95% confidence interval, 1.31-1.62). Additional myectomy did not reduce the risk for reoperation (P=0.92) but significantly increased the risk of a complete heart block requiring pacemaker implantation (8.1% versus 1.7%; P=0.005). CONCLUSIONS: Survival is excellent after surgery for discrete subaortic stenosis; however, reoperation for recurrent discrete subaortic stenosis is not uncommon. Over time, the left ventricular outflow tract gradient slowly increases and mild aortic regurgitation is common, although generally nonprogressive over time. Myectomy does not show additional advantages, and because it is associated with an increased risk of complete heart block, it should not be performed routinely.
Assuntos
Fatores Etários , Estenose Subaórtica Fixa/mortalidade , Estenose Subaórtica Fixa/cirurgia , Progressão da Doença , Adolescente , Adulto , Insuficiência da Valva Aórtica/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
AIMS: Discrete subaortic stenosis (DSS) is often diagnosed early in life and known for its sometimes rapid haemodynamic progression in childhood and strong association with aortic regurgitation (AR). However, data about the evolution of DSS in adulthood are scarce. Therefore, we aimed to evaluate the natural history of DSS, and identify risk factors for the progression of DSS, AR, and intervention-free survival. METHODS AND RESULTS: Conservatively managed adult DSS patients were included in this retrospective multicentre cohort study. Mixed-effects and joint models were used to assess the progression of DSS and AR, and intervention-free survival. Longitudinal natural history data were available for 149 patients [age 20 (IQR: 18-34) years, 48% male]. Sixty patients (40.3%) had associated congenital heart defects (CHDs). The median follow-up duration was 6.3 (IQR: 3.0-12.4) years. The baseline peak left ventricular outflow tract (LVOT) gradient was 32.3 ± 17.0 mmHg and increased by 0.8 ± 0.1 mmHg/year. While the baseline LVOT gradient (P = 0.891) or age (P = 0.421) did not influence the progression rate, the presence of associated CHD was associated with faster progression (P = 0.005). Mild AR was common (58%), but did not significantly progress over time (P = 0.701). The median intervention-free survival was 16 years and associated with the baseline LVOT gradient [hazard ratio (HR) = 3.9 (95% CI: 2.0-7.6)], DSS progression [HR = 2.6 (95% CI: 2.0-3.5)], and AR [HR = 6.4 (95% CI 2.6-15.6)]. CONCLUSION: In contrast to children, DSS progresses slowly in adulthood. In particular, patients with associated CHD are at risk for faster progression and should be monitored cautiously. Discrete subaortic stenosis progression is not influenced by the baseline LVOT gradient or age. Mild AR is common, but non-progressive over time.
Assuntos
Estenose Subaórtica Fixa/etiologia , Adolescente , Adulto , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/mortalidade , Anuloplastia da Valva Cardíaca/mortalidade , Anuloplastia da Valva Cardíaca/estatística & dados numéricos , Estenose Subaórtica Fixa/mortalidade , Estenose Subaórtica Fixa/cirurgia , Progressão da Doença , Feminino , Seguimentos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/mortalidade , Implante de Prótese de Valva Cardíaca/mortalidade , Implante de Prótese de Valva Cardíaca/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: Aneurysms-osteoarthritis syndrome (AOS), caused by SMAD3 mutations, is a recently described autosomal-dominant syndrome characterized by arterial aneurysms, tortuosity, and aortic dissections in combination with osteoarthritis. Our objective was to evaluate the AOS-related vascular consequences in the visceral and iliac arteries and raise awareness for this aggressive syndrome among vascular specialists. METHODS: All AOS patients were monitored regularly according to our clinical AOS protocol. The study included those with one or more visceral aneurysms or tortuosity, or both. Clinical and surgical data were obtained from record abstraction. RESULTS: The study included 17 AOS patients (47% men) aged 47±13 years. A total of 73 aneurysms were encountered, of which 46 were located in the abdomen. The common iliac artery was most commonly affected (37%), followed by the superior mesenteric artery (15%), celiac trunk (11%), and splenic artery (9%). Rapid aneurysm growth≤1 year was found in three arteries (gastric, hepatic, and vertebral artery). Furthermore, arterial tortuosity was noted in 94% of patients. Four patients underwent six elective (endo) vascular interventions for aneurysms in the iliac, hepatic, gastric, or splenic artery, without major perioperative or postoperative complications. CONCLUSIONS: AOS predisposes patients to widespread visceral and iliac artery aneurysms and extreme arterial tortuosity. Early elective aneurysm repair should be considered because the risk of aneurysm rupture is estimated to be very high and elective (endo) vascular interventions were not complicated by fragility of arterial tissue. Given the aggressive behavior of AOS, it is of utmost importance that vascular specialists are aware of this new syndrome.
Assuntos
Aneurisma , Aneurisma Ilíaco , Osteoartrite , Vísceras/irrigação sanguínea , Adulto , Aneurisma/diagnóstico , Aneurisma/genética , Aneurisma/cirurgia , Progressão da Doença , Procedimentos Cirúrgicos Eletivos , Procedimentos Endovasculares/efeitos adversos , Feminino , Predisposição Genética para Doença , Humanos , Aneurisma Ilíaco/diagnóstico , Aneurisma Ilíaco/genética , Aneurisma Ilíaco/cirurgia , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Osteoartrite/genética , Fenótipo , Estudos Retrospectivos , Proteína Smad3/genética , Síndrome , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversosRESUMO
BACKGROUND: The aim of this study was to evaluate the natural progression of aortic dilatation and its association with aortic valve stenosis (AoS) in patients with bicuspid aortic valve (BAV). METHODS: Prospective study of aorta dilatation in patients with BAV and AoS using cardiac magnetic resonance (CMR). Aortic root, ascending aorta, aortic peak velocity, left ventricular systolic and diastolic function and mass were assessed at baseline and at 3-year follow-up. RESULTS: Of the 33 enrolled patients, 5 needed surgery, while 28 patients (17 male; mean age: 31 ± 8 years) completed the study. Aortic diameters significantly increased at the aortic annulus, sinus of Valsalva and tubular ascending aorta levels (P < 0.050). The number of patients with dilated tubular ascending aortas increased from 32 % to 43 %. No significant increase in sino-tubular junction diameter was observed. Aortic peak velocity, ejection fraction and myocardial mass significantly increased while the early/late filling ratio significantly decreased at follow-up (P < 0.050). The progression rate of the ascending aorta diameter correlated weakly with the aortic peak velocity at baseline (R (2) = 0.16, P = 0.040). CONCLUSION: BAV patients with AoS showed a progressive increase of aortic diameters with maximal expression at the level of the tubular ascending aorta. The progression of aortic dilatation correlated weakly with the severity of AoS.
Assuntos
Aorta/patologia , Estenose da Valva Aórtica/patologia , Dilatação Patológica/patologia , Doenças das Valvas Cardíacas/patologia , Imagem Cinética por Ressonância Magnética/métodos , Adulto , Valva Aórtica/anormalidades , Valva Aórtica/patologia , Doença da Válvula Aórtica Bicúspide , Dilatação Patológica/complicações , Doenças das Valvas Cardíacas/complicações , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Aneurysms-osteoarthritis syndrome (AOS) is a new autosomal dominant syndromic form of thoracic aortic aneurysms and dissections characterised by the presence of arterial aneurysms and tortuosity, mild craniofacial, skeletal and cutaneous anomalies, and early-onset osteoarthritis. AOS is caused by mutations in the SMAD3 gene. METHODS: A cohort of 393 patients with aneurysms without mutation in FBN1, TGFBR1 and TGFBR2 was screened for mutations in SMAD3. The patients originated from The Netherlands, Belgium, Switzerland and USA. The clinical phenotype in a total of 45 patients from eight different AOS families with eight different SMAD3 mutations is described. In all patients with a SMAD3 mutation, clinical records were reviewed and extensive genetic, cardiovascular and orthopaedic examinations were performed. RESULTS: Five novel SMAD3 mutations (one nonsense, two missense and two frame-shift mutations) were identified in five new AOS families. A follow-up description of the three families with a SMAD3 mutation previously described by the authors was included. In the majority of patients, early-onset joint abnormalities, including osteoarthritis and osteochondritis dissecans, were the initial symptom for which medical advice was sought. Cardiovascular abnormalities were present in almost 90% of patients, and involved mainly aortic aneurysms and dissections. Aneurysms and tortuosity were found in the aorta and other arteries throughout the body, including intracranial arteries. Of the patients who first presented with joint abnormalities, 20% died suddenly from aortic dissection. The presence of mild craniofacial abnormalities including hypertelorism and abnormal uvula may aid the recognition of this syndrome. CONCLUSION: The authors provide further insight into the phenotype of AOS with SMAD3 mutations, and present recommendations for a clinical work-up.
Assuntos
Anormalidades Múltiplas/genética , Aneurisma/genética , Osteoartrite/genética , Proteína Smad3/genética , Anormalidades Múltiplas/diagnóstico por imagem , Adolescente , Adulto , Idoso , Aneurisma/diagnóstico por imagem , Anormalidades Cardiovasculares/diagnóstico por imagem , Anormalidades Cardiovasculares/genética , Criança , Códon sem Sentido , Estudos de Coortes , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Osteoartrite/diagnóstico por imagem , Linhagem , Fenótipo , Radiografia , Síndrome , Adulto JovemRESUMO
OBJECTIVES/BACKGROUND: Congenital aortic stenosis (AS) is the most common obstructive left heart lesion in the young adult population and often complicated by aortic dilatation. Our objective was to evaluate accuracy of aortic imaging with transthoracic echocardiography (TTE) compared with cardiac magnetic resonance (CMR). METHODS: Aortic diameters were measured at 4 levels by CMR and TTE. Agreement and concordance were assessed by Pearson's correlation and Bland-Altman analysis. RESULTS: Fifty-nine patients (age 33 ± 8 years; 66% male) with congenital AS and a bicuspid aortic valve (BAV) were included. Aortic diameters were generally smaller with TTE than with CMR. The best correlation was found at the level of the sinotubular junction (R(2) = 0.78) with a bias of 1.46 mm (limits of agreement: -5.47 to +8.39 mm). In patients with an aortic aneurysm >40 mm (n = 29) the correlation and agreement between TTE and CMR were found to be less good when compared with patients with normal aortic diameters, especially at the level of the proximal ascending aorta. The correlation and agreement between both imaging modalities were better in patients with type 1 BAV compared with type 2 BAV. Intra- and interobserver variability was smaller with CMR (1.8-5.9%) compared with TTE (6.9-15.0%). CONCLUSIONS: CMR was found to be superior to TTE for imaging of the aorta in patients with congenital AS, especially at the level of the proximal ascending aorta when an aortic aneurysm is present. Therefore, ideally CMR should be performed at least once to ensure an ascending aortic aneurysm is not missed.
Assuntos
Aorta/diagnóstico por imagem , Aorta/patologia , Estenose da Valva Aórtica/congênito , Estenose da Valva Aórtica/diagnóstico , Ecocardiografia/métodos , Imagem Cinética por Ressonância Magnética/métodos , Adolescente , Adulto , Aneurisma Aórtico/diagnóstico , Estudos de Coortes , Diagnóstico por Imagem/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Adulto JovemAssuntos
Aneurisma/complicações , Aneurisma/diagnóstico , Permeabilidade do Canal Arterial/complicações , Artéria Pulmonar/patologia , Dispositivo para Oclusão Septal , Adulto , Aneurisma/diagnóstico por imagem , Aneurisma/cirurgia , Angiografia , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/cirurgia , Humanos , Masculino , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Marfan syndrome (MFS) and familial non-syndromal thoracic aortic aneurysm and dissection (ns-TAAD) are genetic aortopathies causing aortic dilatation with increased aortic stiffness. Left ventricular (LV) contractility and ventricular-vascular coupling index (VVI) were compared between MFS and ns-TAAD and determinants of VVI were investigated. METHODS AND RESULTS: Patients with MFS (M 57, F 47) and ns-TAAD (M 72, F 39) were studied by echocardiography and compared with controls (M 77, F 71). Aortic geometry, hemodynamics, LV work, LV contractility (end-systolic elastance [Ees]), and VVI were documented. Aortic sinuses were equally dilated in MFS (19.7±2.4) and ns-TAAD (19.8±1.8) compared to controls (16.2±1.4 mm·m-2, P<0.001). Aortic stiffness index was increased in MFS (9.7±5.1) and ns-TAAD (10.8±4.7) versus controls (5.4±2.0, P<0.01); LV stroke work was unchanged in MFS (436±74) compared to controls (435±60) but increased in ns-TAAD (492±109 mJ·m-2 P<0.01). The LV Ees was reduced in MFS (1.32±0.19) compared to controls (1.65±0.29 mm Hg·mL-1, P<0.01) but increased in ns-TAAD (1.83±0.30, P<0.01) and VVI was abnormal in MFS (0.71±0.11) compared to controls (0.62±0.07, P<0.01) and ns-TAAD (0.62±0.09). Treatment with ß-blockers was associated with partial normalization of VVI in MFS. A VVI ≥0.8 was associated with increased risk of death and heart failure in MFS. CONCLUSIONS: Left ventricular contractility and ventricular-vascular coupling are abnormal in MFS but preserved in ns-TAAD, and are independent of aortic stiffness, consistent with intrinsic impairment of myocardial contractility in MFS.
Assuntos
Aneurisma da Aorta Torácica/fisiopatologia , Ventrículos do Coração , Síndrome de Marfan/fisiopatologia , Contração Miocárdica , Rigidez Vascular , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Aneurisma da Aorta Torácica/tratamento farmacológico , Aneurisma da Aorta Torácica/etiologia , Austrália/epidemiologia , Dilatação Patológica , Ecocardiografia , Ecocardiografia Doppler , Feminino , Insuficiência Cardíaca/epidemiologia , Hemodinâmica , Humanos , Masculino , Síndrome de Marfan/complicações , Síndrome de Marfan/tratamento farmacológico , Pessoa de Meia-Idade , Mortalidade , Seio Aórtico/patologia , Função Ventricular Esquerda , Adulto JovemRESUMO
BACKGROUND: Non-syndromal thoracic aortic aneurysm and dissection (ns-TAAD) is a genetic aortopathy, with uncertain incidence. This study documented the incidence of ns-TAAD and outcomes of family screening over 15years. METHODS: Consecutive series of 2385 patients with aortic disease in prospective registry (2000 to 2014), including 675 undergoing surgery. Diagnosis of ns-TAAD included family history, aortic imaging, tissue pathology and mutation testing. Screening was offered to relatives of ns-TAAD probands, with follow-up for affected individuals. RESULTS: There were 270 ns-TAAD probands (74% males), including 116 (43%) presenting with aortic dissection. Among surgical cases, a diagnosis of ns-TAAD was established for 116 (17%). Age of probands was 50.4±14.1years, with aortic diameter of 51±12mm. Screening of 581 at-risk relatives identified 216 new ns-TAAD cases (detection rate=37%). Among 71 probands with known family history, screening identified 130 new affected relatives and among 53 probands with no family history, screening identified 86 new affected relatives. Mean age of new affected relatives at diagnosis was 44±18years, with aortic diameter of 42±7mm, including 42 with diameter>50mm. Ten-year mortality was similar for probands without dissection (7.7±3.1%) and new affected relatives (11.4±4.0%) but greater for probands surviving initial dissection (27.6±7.8%, p=0.003). CONCLUSIONS: Up to 1 in 6 patients undergoing aortic surgery have features of ns-TAAD, frequently presenting as aortic dissection but at later age than other genetic aortopathies. Family screening identifies affected relatives in up to half of ns-TAAD probands, many of whom already have significant aortic dilatation.
Assuntos
Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/epidemiologia , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/epidemiologia , Programas de Rastreamento/métodos , Adulto , Idoso , Dissecção Aórtica/genética , Aneurisma da Aorta Torácica/genética , Estudos de Coortes , Família , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Adulto JovemRESUMO
BACKGROUND: Genetic aortopathy (GA) underlies thoracic aortic aneurysms (TAA) in younger adults. Comparative survival and predictors of outcomes in nonsyndromic TAA (NS-TAA) are incompletely defined compared to Marfan syndrome (MFS) and bicuspid aortic valve (BAV). OBJECTIVES: The study sought to compare survival and clinical outcomes for individuals with NS-TAA, MFS, and BAV. METHODS: From 1988 to 2014, all patients presenting with GA 16 to 60 years of age were enrolled in a prospective study of clinical outcomes. Risk factors for death and aortic dissection were identified by Cox proportional hazards modeling and a mortality risk score developed. RESULTS: Diagnosis of GA was made for 760 patients (age 36.9 ± 13.6 years, 26.8% female; NS-TAA, n = 311; MFS, n = 221; BAV, n = 228). MFS patients were younger than NS-TAA and BAV. Presentation with aortic dissection was more common for NS-TAA than MFS or BAV. The 687 patients surviving >30 days after presentation were followed for a median of 7 years. Calculated 10-year mortality was 7.8% for NS-TAA, 8.7% for MFS, and 3.5% for BAV (NS-TAA and MFS vs. BAV p <0.05). Factors associated with all-cause mortality were MFS (p = 0.04), age at presentation, and family history of dissection. CONCLUSIONS: Clinical outcomes for MFS and NS-TAA are similar but worse than BAV. Independent predictors of mortality, including family history of aortic dissection and age, can be included in an Aortopathy Mortality Risk Score to predict survival. Management of NS-TAA, including surgical intervention, should be similar to that of MFS.
Assuntos
Aneurisma da Aorta Torácica/complicações , Dissecção Aórtica/complicações , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/patologia , Síndrome de Marfan/complicações , Adolescente , Adulto , Dissecção Aórtica/mortalidade , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/mortalidade , Valva Aórtica/patologia , Austrália/epidemiologia , Doença da Válvula Aórtica Bicúspide , Dilatação Patológica , Feminino , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/mortalidade , Humanos , Masculino , Síndrome de Marfan/mortalidade , Síndrome de Marfan/cirurgia , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Procedimentos Cirúrgicos Vasculares/métodos , Adulto JovemRESUMO
Children with perinatally acquired parenchymal haemorrhage are thought to have better visual perceptual skills than those with leukomalacia. We examined seven prematurely born children with parenchymal haemorrhage and 14 with grades 2-4 leukomalacia, at the age of 5 years. Clinical and magnetic resonance imaging parameters were related to visual perceptual performance assessed with the L94, using performance age. Belonging to the leukomalacia group, the inability to walk, a diminished peritrigonal white matter, a high degree of gliosis and cortical damage were associated with poorer visuo-perceptual skills. Enlarged lateral ventricles, confirming the findings of Melhelm (Radiology 214 (2000) 199), were associated with both cognitive, perceptual and motor problems and probably reflect the considerable extent of the brain damage. Specific factors protecting against visual perceptual impairment were a preserved volume of the right optical radiation and of the splenium of the corpus callosum. Children with leukomalacia are at considerable risk of visual perceptual impairment. Children with right-sided parenchymal haemorrhages also appear to be at risk although they function much better due to better motor and cognitive skills.
Assuntos
Traumatismos do Nascimento/complicações , Isquemia Encefálica/complicações , Encéfalo/fisiopatologia , Hemorragia Cerebral/complicações , Leucomalácia Periventricular/complicações , Transtornos da Visão/etiologia , Traumatismos do Nascimento/patologia , Traumatismos do Nascimento/fisiopatologia , Encéfalo/patologia , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Hemorragia Cerebral/patologia , Hemorragia Cerebral/fisiopatologia , Criança , Pré-Escolar , Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Corpo Caloso/patologia , Corpo Caloso/fisiopatologia , Feminino , Lateralidade Funcional/fisiologia , Transtornos Neurológicos da Marcha/patologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Recém-Nascido , Doenças do Recém-Nascido/patologia , Doenças do Recém-Nascido/fisiopatologia , Ventrículos Laterais/patologia , Leucomalácia Periventricular/patologia , Leucomalácia Periventricular/fisiopatologia , Imageamento por Ressonância Magnética , Fibras Nervosas Mielinizadas/patologia , Gravidez , Prognóstico , Fatores de Risco , Telencéfalo/patologia , Telencéfalo/fisiopatologia , Transtornos da Visão/patologia , Transtornos da Visão/fisiopatologia , Vias Visuais/patologia , Vias Visuais/fisiopatologiaRESUMO
We describe three cases where Marfan syndrome was suspected, but genetic tests were negative. Two patients, a 38-year-old male and a 45-year-old female, were asymptomatic, but were referred to a clinical geneticist because multiple family members had died of aortic dissections at a young age. The third patient, a 55-year-old female, has been monitored for the past 26 years due to mild aortic dilatation and mitral valve prolapse after three brothers had died suddenly. At screening, all these patients were diagnosed with multiple vascular abnormalities and osteoarthritis. Pathogenic SMAD3 mutations were identified as the cause of the vascular catastrophes in these families. SMAD3 mutations cause aneurysms-osteoarthritis syndrome, an autosomal dominant disorder characterized by aneurysms, dissections and tortuosity throughout the arterial tree, early-onset osteoarthritis and mild craniofacial features. These case descriptions emphasize the importance of timely recognition of aneurysms-osteoarthritis syndrome, as this syndrome causes more aggressive and widespread cardiovascular disease than Marfan syndrome.
Assuntos
Anormalidades Múltiplas/diagnóstico , Aneurisma/diagnóstico , Doenças Cardiovasculares/diagnóstico , Osteoartrite/diagnóstico , Anormalidades Múltiplas/genética , Adulto , Aneurisma/genética , Doenças Cardiovasculares/genética , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/genética , Pessoa de Meia-Idade , Mutação , Osteoartrite/genética , Proteína Smad3/genética , SíndromeRESUMO
BACKGROUND: Aneurysms-osteoarthritis syndrome (AOS), caused by SMAD3 mutations, is a recently described autosomal dominant condition characterized by aneurysms throughout the arterial tree in combination with osteoarthritis. The objective of the present study was to evaluate progression rate of aortic dilation and surgical outcome in AOS patients. METHODS: All AOS patients are regularly monitored according to our clinical AOS protocol. Patients with at least two follow-up visits or who underwent aortic root surgery during follow-up were included in this cohort study. Clinical and surgical data were obtained from chart abstraction. RESULTS: We included 22 patients (aged 38 ± 15 years; 41% male) with the molecular diagnosis of AOS. Follow-up duration was 3.3 years (interquartile range, 1.6 to 5.1). In the 17 patients who were managed conservatively, aortic root diameter increased from 37.5 ± 5.1 mm at baseline to 40.3 ± 6.2 mm at follow-up (p = 0.008). Progression rate of aortic dilation was highest at the level of the sinus of Valsalva (2.5 ± 5.8 mm per year) and significantly correlated with the initial diameter (r = 0.603, p = 0.017). Ten patients successfully underwent valve-sparing aortic root replacement, 5 after previous watchful waiting. Mean preoperative aortic diameter was 46.6 ± 4.0 mm. The operations were not complicated by fragility of tissue. After a postoperative period of 2.8 years (interquartile range, 0.7 to 5.4), no mortality or reoperations had occurred, and all patients remained asymptomatic. CONCLUSIONS: Aneurysm growth in AOS patients can be fast and unpredictable, warranting extensive and frequent cardiovascular monitoring. Valve-sparing aortic root replacement is a safe and effective procedure for the management of aortic root aneurysms in AOS patients.
Assuntos
Aneurisma da Aorta Torácica/cirurgia , Osteoartrite , Adulto , Aneurisma/cirurgia , Progressão da Doença , Feminino , Humanos , Masculino , Síndrome , Fatores de TempoRESUMO
BACKGROUND: Congenital aortic stenosis (AS) is the most common obstructive left-sided cardiac lesion in young adults, however little is known about the progression in adults. Therefore, we aimed to evaluate the progression rate of AS and aortic dilatation in a large multicenter retrospective cohort of asymptomatic young adults with congenital valvular AS. METHODS: Data were obtained from chart abstraction. Linear mixed-effects models were used to evaluate the progression of AS and aortic dilatation over time. A joint model combining longitudinal echocardiographic and survival data was used for survival analysis. RESULTS: A total of 414 patients (age 29 ± 10 years, 68% male) were included. Median follow-up duration was 4.1 (2.5-5.1) years (1587 patient-years). Peak aortic velocity was 3.4 ± 0.7 m/s at baseline and did not change over time in the total patient population (-0.01 ± 0.03 m/s/year). Increased left ventricular mass was significantly associated with faster AS progression (p<0.001). Aortic dilatation was present in 34% at baseline and 48% at follow-up (p<0.001). The aortic diameter linearly increased over time with a rate of 0.7 ± 0.2mm/year. Rate of aortic dissection was 0.06% per patient-year. Seventy patients required an aortic valve intervention (4.4% per patient-year), with AS progression rate as most powerful predictor (HR 5.11 (95% CI 3.47-7.53)). CONCLUSIONS: In the majority of patients with mild-to-moderate congenital AS, AS severity does not progress over time. However patients with left ventricular hypertrophy are at risk for faster progression and should be monitored carefully. Although aortic dissections rarely occur, aortic dilatation is common and steadily progresses over time, warranting serial aortic imaging.
Assuntos
Estenose da Valva Aórtica/diagnóstico , Valva Aórtica/anormalidades , Valva Aórtica/patologia , Progressão da Doença , Adulto , Estenose da Valva Aórtica/mortalidade , Bases de Dados Factuais/tendências , Feminino , Seguimentos , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Adulto JovemRESUMO
OBJECTIVES: The purpose of this study was describe the cardiovascular phenotype of the aneurysms-osteoarthritis syndrome (AOS) and to provide clinical recommendations. BACKGROUND: AOS, caused by pathogenic SMAD3 variants, is a recently described autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis. METHODS: AOS patients in participating centers underwent extensive cardiovascular evaluation, including imaging, arterial stiffness measurements, and biochemical studies. RESULTS: We included 44 AOS patients from 7 families with pathogenic SMAD3 variants (mean age: 42 ± 17 years). In 71%, an aortic root aneurysm was found. In 33%, aneurysms in other arteries in the thorax and abdomen were diagnosed, and in 48%, arterial tortuosity was diagnosed. In 16 patients, cerebrovascular imaging was performed, and cerebrovascular abnormalities were detected in 56% of them. Fifteen deaths occurred at a mean age of 54 ± 15 years. The main cause of death was aortic dissection (9 of 15; 60%), which occurred at mildly increased aortic diameters (range: 40 to 63 mm). Furthermore, cardiac abnormalities were diagnosed, such as congenital heart defects (6%), mitral valve abnormalities (51%), left ventricular hypertrophy (19%), and atrial fibrillation (22%). N-terminal brain natriuretic peptide (NT-proBNP) was significantly higher in AOS patients compared with matched controls (p < 0.001). Aortic pulse wave velocity was high-normal (9.2 ± 2.2 m/s), indicating increased aortic stiffness, which strongly correlated with NT-proBNP (r = 0.731, p = 0.005). CONCLUSIONS: AOS predisposes patients to aggressive and widespread cardiovascular disease and is associated with high mortality. Dissections can occur at relatively mildly increased aortic diameters; therefore, early elective repair of the ascending aorta should be considered. Moreover, cerebrovascular abnormalities were encountered in most patients.