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Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogenic COL3A1 variant diagnosed at age <50 years were included from 2 institutions and the GenTAC Registry (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions). Height-adjusted vertebral artery tortuosity index (VTI-h) using magnetic resonance or computed tomography angiography was calculated. Associations between VTI-h and outcomes of (1) cardiovascular events (arterial dissection/rupture, aneurysm requiring intervention, stroke), or (2) hollow organ collapse/rupture at age <50 years were evaluated using receiver operator curve analysis (using outcome by age 30 years) and mixed-effects Poisson regression for incidence rate ratios. Of 65 subjects (54% male), median VTI-h was 12 (interquartile range, 8-16). Variants were missense in 46%, splice site in 31%, and null/gene deletion in 14%. Thirty-two subjects (49%) had 59 events, including 28 dissections, 5 arterial ruptures, 4 aneurysms requiring intervention, 4 strokes, 11 hollow organ ruptures, and 7 pneumothoraces. Receiver operator curve analysis suggested optimal discrimination at VTI-h ≥15.5 for cardiovascular events (sensitivity 70%, specificity 76%) and no association with noncardiovascular events (area under the curve, 0.49 [95% CI, 0.22-0.78]). By multivariable analysis, older age was associated with increased cardiovascular event rate while VTI-h ≥15.5 was not (incidence rate ratios, 1.79 [95% CI, 0.76-4.24], P=0.185). However, VTI-h ≥15.5 was associated with events among those with high-risk variants <40 years (incidence rate ratios, 4.14 [95% CI, 1.13-15.10], P=0.032), suggesting effect modification by genotype and age. Conclusions Increased arterial tortuosity is associated with a higher incidence rate of cardiovascular events in Vascular Ehlers-Danlos syndrome. Vertebral tortuosity index may be a useful biomarker for prognosis when evaluated in conjunction with genotype and age.
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Disección Aórtica , Síndrome de Ehlers-Danlos Tipo IV , Síndrome de Loeys-Dietz , Humanos , Masculino , Persona de Mediana Edad , Adulto , Femenino , ArteriasRESUMEN
BACKGROUND: Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes. OBJECTIVES: This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene. METHODS: A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, and location of recruitment. RESULTS: Significant differences in aortic event risk were identified among the smooth muscle contraction genes (ACTA2, MYLK, and PRKG1; P = 0.002) and among the genes for Loeys-Dietz syndrome, which encode proteins in the transforming growth factor (TGF)-ß pathway (SMAD3, TGFB2, TGFBR1, and TGFBR2;P < 0.0001). Cumulative incidence of type A aortic dissection was higher than elective aneurysm surgery in patients with variants in ACTA2, MYLK, PRKG1, and SMAD3; in contrast, patients with TGFBR2 variants had lower cumulative incidence of type A aortic dissection than elective aneurysm surgery. Cumulative incidence of type B aortic dissection was higher for ACTA2, PRKG1, and TGFBR2 than other genes. After adjusting for proband status, sex, and recruitment location, specific variants in ACTA2 and TGFBR2 were associated with substantially higher risk of aortic event with childhood onset. CONCLUSIONS: Gene- and variant-specific data on aortic events in individuals with HTAD support personalized aortic surveillance and clinical management.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Disección Aórtica/genética , Aneurisma de la Aorta Torácica/genética , Niño , Humanos , Mutación , Receptor Tipo II de Factor de Crecimiento Transformador beta/genética , Estudios RetrospectivosRESUMEN
Importance: Early data revealed a mortality rate of 1% to 2% per hour for type A acute aortic dissection (TAAAD) during the initial 48 hours. Despite advances in diagnostic testing and treatment, this mortality rate continues to be cited because of a lack of contemporary data characterizing early mortality and the effect of timely surgery. Objective: To examine early mortality rates for patients with TAAAD in the contemporary era. Design, Setting, and Participants: This cohort study examined data for patients with TAAAD in the International Registry of Acute Aortic Dissection between 1996 and 2018. Patients were grouped according to the mode of their intended treatment, surgical or medical. Exposure: Surgical treatment. Main Outcomes and Measures: Mortality was assessed in the initial 48 hours after hospital arrival using Kaplan-Meier curves. In-hospital complications were also evaluated. Results: A total of 5611 patients with TAAAD were identified based on intended treatment: 5131 (91.4%) in the surgical group (3442 [67.1%] male; mean [SD] age, 60.4 [14.1] years) and 480 (8.6%) in the medical group (480 [52.5%] male; mean [SD] age, 70.9 [14.7] years). Reasons for medical management included advanced age (n = 141), comorbidities (n = 281), and patient preference (n = 81). Over the first 48 hours, the mortality for all patients in the study was 5.8%. Among patients who were medically managed, mortality was 0.5% per hour (23.7% at 48 hours). For those whose intended treatment was surgical, 48-hour mortality was 4.4%. In the surgical group, 51 patients (1%) died before the operation. Conclusions and Relevance: In this study, the overall mortality rate for TAAAD was 5.8% at 48 hours. For patients in the medical group, TAAAD had a mortality rate of 0.5% per hour (23.7% at 48 hours). However, among those in the surgical group, 48-hour mortality decreased to 4.4%.
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Disección Aórtica , Enfermedad Aguda , Anciano , Disección Aórtica/epidemiología , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de RegistrosRESUMEN
Hereditary hemorrhagic telangiectasia (HHT) is characterized by arteriovenous malformations and telangiectasia, with primary clinical manifestations of epistaxis and gastrointestinal bleeding and resultant anemia. HHT negatively affects health-related quality of life (HR-QoL); however, existing tools to measure HR-QoL are not HHT specific. Our objective was to develop an HHT-specific HR-QoL (HHT-QoL) instrument and evaluate its performance in a cross-sectional survey of individuals with HHT. Four HHT-specific questions were developed to evaluate the impact of HHT on productivity and social and personal interactions. An anonymous e-mail survey was conducted through Cure HHT. Participants also indicated their perceived HHT severity and completed 3 Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires: Discretionary Social Activities, Social Roles, and Emotional Distress. Complete data were available for 290 participants who self-identified their HHT severity as mild (29%), moderate (46%), or severe (25%). The HHT-QoL scale was reliable (Cronbach's-α, 0.83). Principal components analysis indicated the instrument was unidimensional. Participants had low levels of QoL with their ability to participate in discretionary social activities (PROMIS mean 36.4 [standard deviation 14.3]) and perform in social roles (41.5 [17.2]), and the presence of a high level of emotional distress (64.8 [24.2]). The HHT-QoL score correlated negatively with PROMIS Discretionary Social Activities (r = -0.65) and Social Roles (r = -0.68) and positively correlated with PROMIS Emotional Distress (r = 0.51). In conclusion, the 4-item HHT-QoL instrument provides valuable insight and may be a useful addition to future clinical research in HHT.
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Telangiectasia Hemorrágica Hereditaria , Estudios Transversales , Epistaxis/psicología , Humanos , Calidad de Vida , Encuestas y Cuestionarios , Telangiectasia Hemorrágica Hereditaria/psicologíaRESUMEN
BACKGROUND: The GenTAC (Genetically Triggered Thoracic Aortic Aneurysm and Cardiovascular Conditions) Registry enrolled patients with genetic aortopathies between 2007 and 2016. OBJECTIVES: The purpose of this study was to compare age distribution and probability of elective surgery for proximal aortic aneurysm, any dissection surgery, and cardiovascular mortality among aortopathy etiologies. METHODS: The GenTAC study had a retrospective/prospective design. Participants with bicuspid aortic valve (BAV) with aneurysm (n = 879), Marfan syndrome (MFS) (n = 861), nonsyndromic heritable thoracic aortic disease (nsHTAD) (n = 378), Turner syndrome (TS) (n = 298), vascular Ehlers-Danlos syndrome (vEDS) (n = 149), and Loeys-Dietz syndrome (LDS) (n = 121) were analyzed. RESULTS: The 25% probability of elective proximal aortic aneurysm surgery was 30 years for LDS (95% CI: 18-37 years), followed by MFS (34 years; 95% CI: 32-36 years), nsHTAD (52 years; 95% CI: 48-56 years), and BAV (55 years; 95% CI: 53-58 years). Any dissection surgery 25% probability was highest in LDS (38 years; 95% CI: 33-53 years) followed by MFS (51 years; 95% CI: 46-57 years) and nsHTAD (54 years; 95% CI: 51-61 years). BAV experienced the largest relative frequency of elective surgery to any dissection surgery (254/33 = 7.7), compared with MFS (273/112 = 2.4), LDS (35/16 = 2.2), or nsHTAD (82/76 = 1.1). With MFS as the reference population, risk of any dissection surgery or cardiovascular mortality was lowest in BAV patients (HR: 0.13; 95% CI: 0.08-0.18; HR: 0.13; 95%: CI: 0.06-0.27, respectively). The greatest risk of mortality was seen in patients with vEDS. CONCLUSIONS: Marfan and LDS cohorts demonstrate age and event profiles congruent with the current understanding of syndromic aortopathies. BAV events weigh toward elective replacement with relatively few dissection surgeries. Nonsyndromic HTAD patients experience near equal probability of dissection vs prophylactic surgery, possibly because of failure of early diagnosis.
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Disección Aórtica , Enfermedad de la Válvula Aórtica Bicúspide , Síndrome de Ehlers-Danlos , Síndrome de Loeys-Dietz , Síndrome de Marfan , Disección Aórtica/epidemiología , Disección Aórtica/genética , Disección Aórtica/cirugía , Síndrome de Ehlers-Danlos/complicaciones , Humanos , Síndrome de Loeys-Dietz/complicaciones , Síndrome de Loeys-Dietz/epidemiología , Síndrome de Loeys-Dietz/genética , Síndrome de Marfan/complicaciones , Síndrome de Marfan/genética , Síndrome de Marfan/cirugía , Estudios Prospectivos , Sistema de Registros , Estudios RetrospectivosRESUMEN
BACKGROUND: Previous work has demonstrated that more than one-half of acute type A aortic dissections (ATADs) occur at a maximal aortic diameter (MAD) of <5.5 cm. However, no analysis has investigated whether ATAD risk at smaller MADs is more common with modest dilation of the aortic root (AR) or supracoronary ascending aorta (AA) in patients without genetically triggered aortopathy. OBJECTIVES: This study sought to determine if the segment of modest aortic dilation affects risk of ATAD. METHODS: Using the International Registry of Acute Aortic Dissection (IRAD) database from May 1996 to October 2016, we identified 667 ATAD patients with MAD <5.5 cm. Patients were stratified by location of the largest proximal aortic segment (AR or AA). Patients with known genetically triggered aortopathy were excluded. MADs at time of dissection were compared between AR and AA groups. Secondary outcomes included operation, postoperative outcomes, and long-term survival. RESULTS: Of patients with ATAD at an MAD <5.5 cm, 79.5% (n = 530) were in the AA group and 20.5% (n = 137) in the AR group. Modestly dilated ARs (median MAD 4.6 cm [IQR: 4.1-5.0 cm]) dissected at a significantly smaller diameter than modestly dilated AAs (median MAD 4.8 cm [IQR: 4.4-5.1 cm]) (P < 0.01). AR patients were significantly younger than AA patients (58.5 ± 13.0 years vs 63.2 ± 13.3 years; P < 0.01) and more commonly male (78% vs 65%; P < 0.01). Postoperative and long-term outcomes did not differ between groups. CONCLUSIONS: ATAD appears to occur at smaller diameters in patients with modest dilation in the AR vs the AA (4.6 vs 4.8 cm). These findings may have implications for future consensus guidelines regarding the management of patients with aortic disease.
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Enfermedades de la Aorta , Disección Aórtica , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Aorta/diagnóstico por imagen , Aorta/cirugía , Humanos , Masculino , Sistema de Registros , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Abnormalities of the capillaries of the digits in hereditary hemorrhagic telangiectasia can be detected by shining through a narrow beam of light through the dorsal side and visualizing the vasculature on the palmar side, a procedure termed transillumination. This study was performed to determine if this method can detect digital vascular abnormalities in aortopathies and arteriopathies. Transillumination was performed in patients with Marfan syndrome (MFS), thoracic aortic aneurysm and dissection (TAAD), vascular Ehlers-Danlos syndrome (vEDS), bicuspid aortic valve with aortopathy, and arteriopathies without aortopathy. Subjects with no known vascular disorders were controls. Digital vascular abnormalities were present in some patients with all of the disorders and were especially frequent in MFS, TAAD, and vEDS. All patients had significantly more digital vascular abnormalities than control subjects. Transillumination can detect vascular abnormalities in digits of patients with a variety of conditions with aortopathy or arteriopathy.
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Disección Aórtica , Síndrome de Ehlers-Danlos , Síndrome de Marfan , Telangiectasia Hemorrágica Hereditaria , Síndrome de Ehlers-Danlos/diagnóstico , Humanos , Síndrome de Marfan/diagnóstico , TransiluminaciónRESUMEN
Marfan syndrome (MFS) is an autosomal dominant, age-related but highly penetrant condition with substantial intrafamilial and interfamilial variability. MFS is caused by pathogenetic variants in FBN1, which encodes fibrillin-1, a major structural component of the extracellular matrix that provides support to connective tissues, particularly in arteries, the pericondrium and structures in the eye. Up to 25% of individuals with MFS have de novo variants. The most prominent manifestations of MFS are asymptomatic aortic root aneurysms, aortic dissections, dislocation of the ocular lens (ectopia lentis) and skeletal abnormalities that are characterized by overgrowth of the long bones. MFS is diagnosed based on the Ghent II nosology; genetic testing confirming the presence of a FBN1 pathogenetic variant is not always required for diagnosis but can help distinguish MFS from other heritable thoracic aortic disease syndromes that can present with skeletal features similar to those in MFS. Untreated aortic root aneurysms can progress to life-threatening acute aortic dissections. Management of MFS requires medical therapy to slow the rate of growth of aneurysms and decrease the risk of dissection. Routine surveillance with imaging techniques such as transthoracic echocardiography, CT or MRI is necessary to monitor aneurysm growth and determine when to perform prophylactic repair surgery to prevent an acute aortic dissection.
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Síndrome de Marfan , Fibrilina-1/genética , Fibrilinas , Humanos , Síndrome de Marfan/complicaciones , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/genética , Proteínas de Microfilamentos/genética , MutaciónRESUMEN
Heritable connective tissue disorders are a group of diseases, each rare, characterized by various combinations of skin, joint, musculoskeletal, organ, and vascular involvement. Although kidney abnormalities have been reported in some connective tissue disorders, they are rarely a presenting feature. Here we present three patients with prominent kidney phenotypes who were found by whole exome sequencing to have variants in established connective tissue genes associated with Loeys-Dietz syndrome and congenital contractural arachnodactyly. These cases highlight the importance of considering connective tissue disease in children presenting with structural kidney disease and also serves to expand the phenotype of Loeys-Dietz syndrome and possibly congenital contractural arachnodactyly to include cystic kidney disease and cystic kidney dysplasia, respectively.
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Aracnodactilia/genética , Contractura/genética , Fibrilina-2/genética , Síndrome de Loeys-Dietz/genética , Receptor Tipo I de Factor de Crecimiento Transformador beta/genética , Proteína Smad2/genética , Adolescente , Aracnodactilia/complicaciones , Aracnodactilia/diagnóstico por imagen , Aracnodactilia/patología , Niño , Tejido Conectivo/patología , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico por imagen , Enfermedades del Tejido Conjuntivo/genética , Enfermedades del Tejido Conjuntivo/patología , Contractura/complicaciones , Contractura/diagnóstico por imagen , Contractura/patología , Predisposición Genética a la Enfermedad , Humanos , Riñón/diagnóstico por imagen , Riñón/patología , Enfermedades Renales Quísticas/complicaciones , Enfermedades Renales Quísticas/genética , Enfermedades Renales Quísticas/patología , Síndrome de Loeys-Dietz/complicaciones , Síndrome de Loeys-Dietz/diagnóstico por imagen , Síndrome de Loeys-Dietz/patología , Masculino , Mutación/genética , Fenotipo , Anomalías Cutáneas/complicaciones , Anomalías Cutáneas/genética , Anomalías Cutáneas/patología , Secuenciación del ExomaRESUMEN
Arachnodactyly, a term used since 1902 to describe abnormally long (spider-like) fingers, is a pathologic feature of several heritable conditions, notably the Marfan syndrome and congenital contractural arachnodactyly. A number of prominent artists, dating from the 16th to the 20th centuries, have depicted subjects with unusually long fingers, sometime associated with elongation of the body, neck and head. El Greco incorporated this style in many paintings. Little evidence supports any subject in any of these paintings as having a congenital deformity.
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Aracnodactilia , Contractura , Síndrome de Marfan , Aracnodactilia/genética , Dedos , Humanos , CuelloRESUMEN
Importance: Women with aortopathy conditions are at risk for pregnancy-related aortic dissection, and these conditions may not be recognized until after the aortic dissection occurs. Objective: To examine the clinical characteristics, imaging features, and outcomes in women with pregnancy-related acute aortic dissection. Design, Setting, and Participants: A cohort study, comprising data from the International Registry of Acute Aortic Dissection (IRAD) (February 1, 1998, to February 28, 2018). The multicenter referral center study included 29 women with aortic dissection during pregnancy or less than 12 weeks post partum in IRAD from 1998 to 2018. Main Outcomes and Measures: Clinical features of pregnancy-related aortic dissection to be studied included underlying aortopathy, aortic size, type of aortic dissection, timing of dissection, hypertension, and previous aortic surgery. Results: A total of 29 women (mean [SD] age, 32 [6] years) had pregnancy-related aortic dissection, representing 0.3% of all aortic dissections and 1% of aortic dissection in women in the IRAD. Among women younger than 35 years, aortic dissection was related to pregnancy in 20 of 105 women (19%). Thirteen women (45%) had type A aortic dissection, and 16 women (55%) had type B. Aortic dissection onset was known in 27 women (93%): 15 during pregnancy, 4 in the first trimester, and 11 in the third trimester; 12 were post partum, occurring a mean (SD) of 12.5 (14) days post partum. At type A aortic dissection diagnosis, the mean (SD) aortic diameters were sinus of Valsalva, 54.5 (5) mm and ascending aorta, 54.7 (6) mm. At type B aortic dissection diagnosis, the mean (SD) descending aortic diameter was 32.5 (5) mm. Twenty women (69%) had an aortopathy condition or a positive family history: 13 women (65%) with Marfan syndrome, 2 women (10%) with Loeys-Dietz syndrome, 2 women (10%) with bicuspid aortic valves, 2 women (10%) with a family history of aortic disease, and 1 woman (5%) with familial thoracic aortic aneurysm. Aortopathy was not recognized until after aortic dissection in 47% of the women. Twenty-eight women (97%) survived aortic dissection hospitalization. Conclusions and Relevance: Aortic dissection complicating pregnancy is rare. Most pregnancy-related aortic dissection is due to an aortopathy often not diagnosed until after aortic dissection. In this study, type A aortic dissections were associated with a dilated aorta, and type B aortic dissections often were not. Recognition of underlying conditions and risks for aortic dissection may improve management of pregnancy in women with aortopathy.
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Aneurisma de la Aorta/epidemiología , Disección Aórtica/epidemiología , Complicaciones Cardiovasculares del Embarazo/epidemiología , Trastornos Puerperales/epidemiología , Adulto , Disección Aórtica/complicaciones , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/terapia , Aorta/patología , Aorta Torácica/patología , Aneurisma de la Aorta/complicaciones , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/terapia , Enfermedades de la Aorta/complicaciones , Enfermedad de la Válvula Aórtica Bicúspide/complicaciones , Femenino , Mortalidad Hospitalaria , Humanos , Síndrome de Loeys-Dietz/complicaciones , Síndrome de Marfan/complicaciones , Tamaño de los Órganos , Embarazo , Complicaciones Cardiovasculares del Embarazo/diagnóstico por imagen , Complicaciones Cardiovasculares del Embarazo/terapia , Trastornos Puerperales/diagnóstico por imagen , Trastornos Puerperales/terapia , Sistema de Registros , Seno Aórtico/patología , Enfermedades no Diagnosticadas/complicaciones , Adulto JovenRESUMEN
As exacting as genetic and genomic testing have become, health professionals continue to encounter uncertainty in their applications to medical practice. As examining the human genome at more refined levels increases, so is the likelihood of encountering uncertainty about the meaning of the information. The history of this concept informs how we might confront and deal with uncertainty, and what the future might hold. Precision medicine holds great promise for establishing more accurate diagnoses, directing specific therapy to patients who will most benefit from it, and avoiding treatments in patients who are most likely to suffer adverse consequences, or at best not benefit. But its application depends importantly on the proper interpretation of a person's genotype.
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Predisposición Genética a la Enfermedad , Genoma Humano/genética , Genómica , Pruebas Genéticas , Humanos , Medicina de Precisión , IncertidumbreRESUMEN
BACKGROUND: We determined the frequency of cerebrovascular malformations in a pediatric cohort with hereditary hemorrhagic telangiectasia. METHODS: Retrospective cohort study of 54 children diagnosed with hereditary hemorrhagic telangiectasia at a tertiary care center. All neuroimaging was reviewed to assess for number and types of cerebrovascular malformations and for intracerebral hemorrhage and arterial ischemic stroke. Clinical charts were reviewed for clinical manifestations, genetic mutation, and clinically evident intracerebral hemorrhages and arterial ischemic strokes. RESULTS: Among 54 children with hereditary hemorrhagic telangiectasia with a median age of 3.5 years (interquartile range 0.4 to 7.9 years) at diagnosis, neuroimaging was performed in 52 (96.3%) at a median age of 5.2 years (interquartile range 1.8 to 9 years). Fourteen of 52 imaged children (26.9%) had cerebrovascular malformations. Cerebrovascular malformations included arteriovenous malformations, arteriovenous fistulas, vein of Galen malformations, and developmental venous anomalies. Six of the 14 children with cerebrovascular malformations (42.9%) had multiple malformations. Three children developed new cerebral arteriovenous malformations over time. Six children (11.1%) had clinically evident intracerebral hemorrhage, arterial ischemic stroke, or transient ischemic attack. The three children with intracerebral hemorrhage presented at young ages (4.3 to 7.7 years). CONCLUSIONS: More than a quarter of children with hereditary hemorrhagic telangiectasia who were imaged had cerebrovascular malformations, and overt stroke occurred in more than 10%. Intracerebral hemorrhages can occur in pediatric hereditary hemorrhagic telangiectasia patients at young ages, and new cerebral arteriovenous malformations may develop over time. Early screening with neuroimaging including neurovascular imaging as well as repeat neuroimaging may be warranted in children with hereditary hemorrhagic telangiectasia.
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Fístula Arteriovenosa , Hemorragia Cerebral , Malformaciones Arteriovenosas Intracraneales , Accidente Cerebrovascular Isquémico , Telangiectasia Hemorrágica Hereditaria , Fístula Arteriovenosa/diagnóstico por imagen , Fístula Arteriovenosa/epidemiología , Fístula Arteriovenosa/etiología , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/etiología , Niño , Preescolar , Femenino , Humanos , Lactante , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/epidemiología , Malformaciones Arteriovenosas Intracraneales/etiología , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/etiología , Masculino , Estudios Retrospectivos , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/diagnóstico por imagen , Telangiectasia Hemorrágica Hereditaria/epidemiología , Atención Terciaria de SaludRESUMEN
BACKGROUND: High-resolution chest CT (HRCT) scan is recommended after pulmonary arteriovenous malformation (PAVM) embolotherapy to assess for PAVM persistence and untreated PAVM growth. Graded transthoracic contrast echocardiography (TTCE) predicts the need for embolotherapy in PAVM screening. This study sought to determine whether postembolotherapy graded TTCE can similarly predict the need for repeat embolotherapy. METHODS: Thirty-two patients (8 men and 24 women; mean age, 51.1 ± 12.6 years) with prior PAVM embolotherapy and follow-up HRCT scan were prospectively enrolled. Patients underwent graded TTCE using a validated three-point quantitative grading scale. TTCE grade and HRCT findings were compared. RESULTS: Median time between most recent HRCT scan and TTCE was 7 days (interquartile range, 0-272 days). Thirty patients (94%) had no PAVMs requiring repeat embolotherapy on HRCT scan. Two patients (6%) had PAVMs requiring repeat embolotherapy (feeding artery [FA] ≥ 3 mm), one with untreated PAVM growth and one with treated PAVM persistence. TTCE was positive in 88% of patients (n = 28). All patients (n = 4, 12%) with negative TTCE had no visible PAVMs on HRCT scan. Nine patients (32%) had grade 1 shunt, 10 (35%) had grade 2 shunt, and nine (32%) had grade 3 shunt. No patients with grade 1 shunt had PAVMs amenable to repeat embolotherapy on HRCT scan. All patients (n = 2) with PAVMs requiring repeat embolotherapy (FA ≥ 3 mm) had grade 3 shunt. TTCE grade was significantly associated with PAVM FA diameter (P < .001). CONCLUSIONS: Postembolotherapy graded TTCE can predict the need for repeat embolotherapy on HRCT scan. Patients with negative TTCE and grade 1 shunt may not require HRCT follow-up and can potentially be followed with serial graded TTCE. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02936349; URL: www.clinicaltrials.gov.
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Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/terapia , Ecocardiografía , Embolización Terapéutica/métodos , Tomografía Computarizada por Rayos X , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , RetratamientoRESUMEN
BACKGROUND: Although patients with various types of heritable aortopathy often require distal aortic repair, data are limited regarding the most extensive operations-open thoracoabdominal aortic aneurysm (TAAA) repairs. The objective of this multicenter registry study was to characterize TAAA repairs in a large cohort of patients with different heritable aortic diseases. METHODS: From the 3699 patients enrolled at 8 participating centers in the Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC) Registry, we identified 155 open TAAA repairs in 142 unique patients. We examined data related to clinical characteristics, surgical techniques, and outcomes. RESULTS: The primary diagnoses included Marfan syndrome (n = 76; 54%), familial thoracic aortic aneurysm and dissections (n = 31; 22%), and Loeys-Dietz syndrome (n = 10; 7%). Most repairs were performed for aneurysms associated with aortic dissection (n = 110; 71%). The most common repairs involved the entire descending thoracic aorta with distal extension (21% Crawford extent I and 36% extent II). Adjuncts used during repair varied substantially. The operative mortality rate was 1.3%. Other complications included paraplegia (4%), acute renal failure (5%), and vocal cord paralysis (21%). Reoperation after TAAA repair was required in a subset of cases for early bleeding (n = 15; 10%) and late repair failure (n = 7; 5%). CONCLUSIONS: Open TAAA repairs are necessary in a variety of heritable aortic diseases. These patients often require extensive surgical repair, and a variety of adjunctive techniques are utilized. The risk of repair failure and the need for reoperation in a subset of patients support the need for vigilant long-term surveillance after repair.
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Aorta Abdominal/cirugía , Aorta Torácica/cirugía , Enfermedades de la Aorta/cirugía , Sistema de Registros , Procedimientos Quirúrgicos Vasculares/métodos , Adulto , Aorta Abdominal/anomalías , Aorta Torácica/anomalías , Enfermedades de la Aorta/genética , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Complicaciones Posoperatorias/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Introduction: The revised Ghent nosology presents the classical features of Marfan syndrome. However, behind its familiar face, Marfan syndrome hides less well-known features.Areas covered: The German Marfan Organization listed unusual symptoms and clinical experts reviewed the literature on clinical features of Marfan syndrome not listed in the Ghent nosology. Thereby we identified the following features: (1) bicuspid aortic valve, mitral valve prolapse, pulmonary valve prolapse, tricuspid valve prolapse, (2) heart failure and cardiomyopathy, (3) supraventricular arrhythmia, ventricular arrhythmia, and abnormal repolarization, (4) spontaneous coronary artery dissection, anomalous coronary arteries, and atherosclerotic coronary artery disease, tortuosity-, aneurysm-, and dissection of large and medium-sized arteries, (5) restrictive lung disease, parenchymal lung disease, and airway disorders, (6) obstructive- and central sleep apnea, (7) liver and kidney cysts, biliary tract disease, diaphragmatic hernia, and adiposity, (8) premature labor, and urinary incontinence, (9) myopathy, reduced bone mineral density, and craniofacial manifestations, (10) atrophic scars, (11) caries, and craniomandibular dysfunction, (12) headache from migraine and spontaneous cerebrospinal fluid leakage, (13) cognitive dysfunction, schizophrenia, depression, fatigue, and pain, (14) and activated fibrinolysis, thrombin, platelets, acquired von Willebrand disease, and platelet dysfunction.Expert commentary: Future research, nosologies, and guidelines may consider less well-known features of Marfan syndrome.
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Enfermedades Cardiovasculares/etiología , Síndrome de Marfan/fisiopatología , Huesos/patología , Enfermedades Cardiovasculares/fisiopatología , Humanos , Pulmón/fisiopatologíaRESUMEN
Clinical research studies often leverage various heterogeneous data sources including patient electronic health record, online survey, and genomic data. We introduce a graph-based, data integration and query tool called Carnival. We demonstrate its powerful ability to unify data from these disparate data sources to create datasets for two studies: prevalence and incidence case/control matches for coronary artery disease and controls for Marfan syndrome. We conclude with future directions for Carnival development.