RESUMO
Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately one in 300,000 people. The disorder is characterized by extremely high, life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth, leading to significant premature cardiovascular morbidity and mortality, if left untreated. Homozygous familial hypercholesterolemia is severely underdiagnosed and undertreated in the United States (US), despite guidelines recommendations for universal pediatric lipid screening in children aged 9-11. Early diagnosis and adequate treatment are critical in averting premature cardiovascular disease in individuals affected by HoFH. Yet, an unacceptably high number of people living with HoFH remain undiagnosed, misdiagnosed, and/or receive a late diagnosis, often after a major cardiovascular event. The emergence of novel lipid-lowering therapies, along with the realization that diagnosis is too often delayed, have highlighted an urgency to implement policies that ensure timely detection of HoFH in the US. Evidence from around the world suggests that a combination of universal pediatric screening and cascade screening strategies constitutes an effective approach to identifying heterozygous familial hypercholesterolemia (HeFH). Nevertheless, HoFH and its complications manifest much earlier in life compared to HeFH. To date, little focus has been placed on the detection of HoFH in very young children and/or infants. The 2023 Updated European Atherosclerosis Society Consensus Statement on HoFH has recommended, for the first time, broadening pediatric guidelines to include lipid screening of newborn infants. Some unique aspects of HoFH need to be considered before implementing newborn screening. As such, insights from pilot studies conducted in Europe may provide some preliminary guidance. Our paper proposes a set of actionable measures that states can implement to reduce the burden of HoFH. It also outlines key research and policy gaps that need to be addressed in order to pave the way for universal newborn screening of HoFH in the US.
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Hiperlipoproteinemia Tipo II , Criança , Humanos , LDL-Colesterol/sangue , Homozigoto , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Programas de Rastreamento/métodos , Triagem Neonatal/métodos , Estados Unidos/epidemiologia , Recém-NascidoRESUMO
PURPOSE OF REVIEW: Newborn screening is one of the most successful public health programs of the last century and offers unparalleled access to universal screening for a variety of metabolic and other disorders. Interest in development of newborn screening for lipid disorders has intensified in recent years. Screening newborns for lipid disorders has important implications for the health of the newborn as well as their relatives, and in the case of more common lipid disorders like familial hypercholesterolemia, could have important public health implications. RECENT FINDINGS: Recent studies have demonstrated feasibility of measuring biomarkers for heterozygous familial hypercholesterolemia from newborn screening dried blood spot specimens. Another lipid disorder, cerebrotendinous xanthomatosis, is currently amenable to newborn screening utilizing currently available assays. New research in next-generation sequencing as a primary screen in newborns will also identify both common and rare lipid disorders in newborns. SUMMARY: Historically, newborn screening for lipid disorders was not done for many reasons, but new research has developed testing methods that may successfully identify common and rare lipid disorders. This will impact the health of the newborn but could also impact family members and public health.
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Triagem Neonatal , Humanos , Triagem Neonatal/métodos , Recém-Nascido , Biomarcadores/sangue , Biomarcadores/metabolismoRESUMO
OBJECTIVE: To evaluate distribution profiles of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apoB) as candidate markers of familial hypercholesterolemia in newborns, taking into consideration potential confounding factors, such as gestational age, birth weight, sex, and race. STUDY DESIGN: TC, LDL-C, and apoB were measured from 10â000 residual deidentified newborn dried blood spot cards. Concentrations for each biomarker were reported as multiples of the median, with emphasis on describing the 99th percentile values based on birth weight, gestational age, sex, and race. Seasonal variation of biomarkers was also explored. RESULTS: LDL-C and apoB had distribution curves with tails showing extreme elevation, whereas the distribution of TC was less elevated and had the smallest range. Neonates born at early gestational age and low birth weight had significantly greater 99th percentile of multiples of the median values for apoB but not TC or LDL-C. Differences in biomarker concentration based on sex and race were minimal. All biomarkers showed greatest concentrations in the winter as compared with summer months. CONCLUSIONS: LDL-C and apoB had distribution curves supporting candidacy for neonatal familial hypercholesterolemia screening. Future studies are needed to correlate newborn screening results with molecular testing to validate these 2 biomarkers, along with measured cholesterol levels later in childhood.
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Hiperlipoproteinemia Tipo II , Humanos , Recém-Nascido , LDL-Colesterol , Peso ao Nascer , Hiperlipoproteinemia Tipo II/diagnóstico , Biomarcadores , Apolipoproteínas BRESUMO
BACKGROUND: Familial hypercholesterolemia (FH) is an inherited disease which causes premature atherosclerotic cardiovascular disease. However, less than 10% of individuals with FH have been identified. OBJECTIVE: To assess parental perspectives for inclusion of FH on routine newborn screening (NBS) and to highlight potential benefits, harms, and ethical concerns. METHODS: Telephone interviews of two groups were conducted: 1) parents of children diagnosed with FH, and 2) parents of children diagnosed with a genetic condition through NBS. Stratified purposive sampling was used to ensure adequate representation. The 11 telephone interviews were conducted in 30-min sessions guided by a semi-structured interview script. At the beginning of the interview, participants were educated on the NBS process and FH. The interviews were transcribed verbatim, and a thematic analysis was performed in multiple steps. RESULTS: All interviewees indicated that they would be interested in having their child be screened for FH on the newborn screen. Reasons supporting screening during the newborn period included knowing their child's diagnosis, the ability to screen family members for FH, incorporation of lifestyle changes, and access to preventive care. Negatives surrounding screening during the newborn period included increased stress or anxiety, knowledge, stigma, and the delay from diagnosis to initiation of pharmacotherapy for FH. CONCLUSION: While these interviewees were in favor of NBS for FH, further education of parents and clinicians is needed to ensure proper implementation. The results of this study may be useful to formulate family notification and care protocols for newborns diagnosed with FH and other diseases.
What is already known on this subject? Familial hypercholesterolemia is a common inherited disorder that predisposes to early cardiovascular disease, but most affected individuals are not diagnosed. Childhood cholesterol screening is an effective but underutilized diagnostic tool. Previous studies report parents find childhood cholesterol screening acceptable, but it is not known if screening newborns would also be acceptable.What does this study add? Interviewees found screening newborns for familial hypercholesterolemia acceptable and would agree to screen their own newborn. The ability to screen other family members and access to early treatment were important factors in their decision to screen. Education of clinicians about familial hypercholesterolemia was an important concern raised by interviewees.
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Hiperlipoproteinemia Tipo II , Triagem Neonatal , Criança , Humanos , Recém-Nascido , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Testes Genéticos , Programas de Rastreamento/métodos , Pais , AtitudeRESUMO
OBJECTIVES: The objective of the study was to assess contemporary practice patterns of pediatric cardiologists with respect to cholesterol disorders and smoking-related illness. STUDY DESIGN: We sent 2 anonymous surveys to the members of the American Academy of Pediatrics Section on Cardiology and Cardiac Surgery and the Pediheart online community. The surveys addressed training in and management of cholesterol disorders and smoking-related illness. RESULTS: There were 97 responses to the cholesterol disorders survey. A total of 51.6% reported little or no formal training on cholesterol disorders. A total of 56.4% underestimated the prevalence of familial hypercholesterolemia by at least twofold. A total of 54.7% were at least somewhat comfortable prescribing statins. In 5 clinical vignettes, respondents frequently gave clinical recommendations in line with the 2019 American Heart Association guidelines although both undertreatment and overtreatment were recommended. There were 90 responses to the survey on smoking-related illness. Little or no formal training in nicotine addiction (52.3%) or smoking cessation (60.5%) was reported by respondents. Respondents screened for tobacco use in less than a one-third of hospitalizations and less than two-thirds of outpatient clinic visits. Screening for exposure to secondhand smoke was even less common. Twenty-seven percent of respondents never recommend a household smoking ban for their patients. A total of 83.3% were uncomfortable prescribing medications for their patients for smoking cessation, and 65.5% rarely or never refer patients for smoking cessation assistance. CONCLUSION: Although positioned to address the childhood origins of adult heart disease, those cardiologists surveyed placed a limited emphasis on cholesterol disorders and smoking-related disease in their clinical practice.
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Cardiologia , Cardiopatias , Abandono do Hábito de Fumar , Adulto , Humanos , Criança , Abandono do Hábito de Fumar/métodos , Inquéritos e Questionários , ColesterolRESUMO
BACKGROUND: Inclisiran is a small interfering RNA molecule that reduces low-density lipoprotein cholesterol (LDL-C) by inhibition of proprotein convertase subtilisin/kexin type 9. This subcutaneous, twice-yearly administered agent has been shown to effectively and safely lower LDL-C in adult patients with established atherosclerotic cardiovascular disease, adults at high risk for atherosclerotic cardiovascular disease, as well as in adults with heterozygous familial hypercholesterolaemia. With the current, limited treatment options available to reach treatment goals in children with severe heterozygous familial hypercholesterolaemia, homozygous familial hypercholesterolaemia, or statin intolerance, inclisiran could be a valuable new therapeutic option. OBJECTIVES: The objective of these ongoing studies is to investigate the efficacy, safety, and tolerability of inclisiran in adolescents diagnosed with homozygous familial hypercholesterolaemia (ORION-13) or heterozygous familial hypercholesterolaemia (ORION-16). STUDY DESIGN: ORION-13 and ORION-16 are both two-part (1-year double-blind inclisiran vs. placebo/1 year open-label inclisiran) multicentre trials including adolescents aged 12 to <18 years diagnosed with familial hypercholesterolaemia. ORION-13 will include â¼12 participants diagnosed with homozygous familial hypercholesterolaemia and ORION-16 will include â¼150 participants diagnosed with heterozygous familial hypercholesteroleamia. The primary endpoint is the percentage change in LDL-C from baseline to Day 330. Secondary efficacy and safety endpoints include changes in other lipid parameters and treatment-emergent adverse events as well as laboratory parameters and vital signs. Exploratory endpoints include individual responsiveness of the participants and change in LDL-C according to the type of underlying causal mutation. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov/. Unique identifier: NCT04659863 (ORION-13) and NCT04652726 (ORION-16).
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Anticolesterolemiantes , Doenças Cardiovasculares , Hiperlipoproteinemia Tipo II , Adolescente , Adulto , Anticolesterolemiantes/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Criança , LDL-Colesterol , Método Duplo-Cego , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/genética , RNA Interferente Pequeno/efeitos adversosRESUMO
PURPOSE OF REVIEW: Familial hypercholesterolemia (FH), a common inherited disorder of LDL-C metabolism that predisposes to premature cardiovascular disease, is underdiagnosed. Despite recommendations for screening all children and initiation of lipid-lowering medication beginning at 8-10 years of age, adherence to guidelines is low. Most individuals with FH are inadequately treated, especially women and children. The purpose of this review is to discuss current literature and recommendations for the diagnosis and treatment of heterozygous FH (HeFH) in the pediatric population. RECENT FINDINGS: Twenty-year outcome data demonstrate lower rates of atherosclerotic cardiovascular disease (ASCVD) related events and death in individuals with FH who were treated with statins from childhood, compared to those who initiated statins in adulthood. While diagnosis rates of FH are slowly improving, most clinicians do not adhere to recommendations for cholesterol screening in youth. Identifying youth with FH offers the opportunity for early intervention to prevent ASCVD and identify affected relatives through reverse cascade screening.
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Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Adolescente , Adulto , Aterosclerose/epidemiologia , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Criança , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Programas de RastreamentoRESUMO
Conflicting guidelines regarding universal pediatric cholesterol screening were released between 2011 and 2019, but the impact on screening rates remains understudied. The purpose of this study was to examine trends in pediatric cholesterol screening rates within a single institution in the United States and their association with release of national guidelines, local educational tools, and electronic health record (EHR) modifications. Order placement was defined as ordering a high-density lipoprotein cholesterol level in a patient aged 9-21 years with ≥1 well visit in prior 3 years. Order placement rate (OPR) was calculated per month using 3 months' moving average smoothing and analyzed based on date, patient age, and specialty of ordering clinician. Timing of educational tools, EHR modifications, and national guideline release were analyzed for changes in OPR. Prior to release of 2011 guidelines recommending universal pediatric cholesterol screening, pediatrician OPR was 35% (95% CI: 29-43%) compared to 8% (7-11%) for family physicians. For both specialties, OPR increased after 2011 guidelines, educational initiatives, and EHR changes, but decreased after 2016, with a larger decrease for family physicians (p < 0.001 for all). OPR was consistently higher for pediatricians than for family physicians during the study period, with largest OPR changes correlating with release of guidelines. The findings from the study suggest that conflicting guidelines may contribute to lower overall OPR, and to different screening rates for children cared for by pediatricians compared to family physicians.
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Pediatras , Médicos de Família , Adolescente , Adulto , Criança , Colesterol , Registros Eletrônicos de Saúde , Humanos , Programas de Rastreamento , Padrões de Prática Médica , Estados Unidos , Adulto JovemRESUMO
Heterozygous familial hypercholesterolemia (HeFH) results in significant elevations in LDL-C and premature atherosclerotic cardiovascular disease (ASCVD). Current guidelines recommend add-on proprotein subtilisin/kexin type 9 inhibitor (PCSK9i) therapy for additional LDL-C lowering beyond statins. Data are sparse, however, regarding treatment patterns and barriers relating to PCSK9i in HeFH patients. We examined physician attitudes, use, and barriers for treatment in patients with HeFH. We surveyed 1,000 physicians (500 primary care providers [PCPs] and 500 cardiologists in the US regarding their preferred treatments, experience and barriers associated with using PCSK9is. Cardiologists compared to PCPs were more likely to rank a PCSK9i as most important for an HeFH patient needing additional LDL-C lowering (68.6% vs. 64.8%; p <0.05), as well as prescribing and having a patient on a PCSK9i. PCPs vs. cardiologists were less likely (odds ratio [OR] [95% confidence interval] = 0.46 [0.34-0.63]), private vs. academic practice more likely (OR = 1.53 [1.02-2.28]), and those who would prescribe a PCSK9i in an HeFH patient with (OR = 3.86 [2.57-5.78]) or without (OR = 1.96 [1.40-2.72]) ASCVD needing additional LDL-C reduction beyond a statin were more likely to actually prescribe a PCSK9i. Those practicing in an urban vs. rural setting were less likely (OR = 0.56 [0.34-0.93]), and those indicating they would prescribe a PCKS9i in an HeFH patient with (OR = 2.80 [1.74-4.49]) or without (OR = 1.43 [1.02-2.02]) ASCVD needing additional LDL-C lowering beyond a statin were more likely to face difficulty prescribing a PCSK9i (all p <0.05 to p <0.01). Greater physician education and assistance among both cardiologists and PCPs are needed to address the gaps in understanding and treatment regarding PCSK9is.
Assuntos
Anticolesterolemiantes/uso terapêutico , Cardiologistas , Custos de Medicamentos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Inibidores de PCSK9 , Preferência do Paciente , Médicos de Atenção Primária , Inibidores de Serina Proteinase/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Quimioterapia Combinada , Heterozigoto , Humanos , Hiperlipoproteinemia Tipo II/genética , Seguro Saúde , Autorização Prévia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To describe enrollment characteristics of youth in the Cascade Screening for Awareness and Detection of FH Registry. STUDY DESIGN: This is a cross-sectional analysis of 493 participants aged <18 years with heterozygous familial hypercholesterolemia recruited from US lipid clinics (n = 20) between April 1, 2014, and January 12, 2018. At enrollment, some were new patients and some were already in care. Clinical characteristics are described, including lipid levels and lipid-lowering treatments. RESULTS: Mean age at diagnosis was 9.4 (4.0) years; 47% female, 68% white and 12% Hispanic. Average (SD) highest Low-density lipoprotein cholesterol (LDL-C) was 238 (61) mg/dL before treatment. Lipid-lowering therapy was used by 64% of participants; 56% were treated with statin. LDL-C declined 84 mg/dL (33%) among those treated with lipid-lowering therapy; statins produced the greatest decline, 100 mg/dL (39% reduction). At enrollment, 39% had reached an LDL-C goal, either <130 mg/dL or ≥50% decrease from pre-treatment; 20% of those on lipid-lowering therapy reached both goals. CONCLUSIONS: Among youth enrolled in the Cascade Screening for Awareness and Detection of FH Registry, diagnosis occurred relatively late, only 77% of children eligible for lipid-lowering therapy were receiving treatment, and only 39% of those treated met their LDL-C goal. Opportunities exist for earlier diagnosis, broader use of lipid-lowering therapy, and greater reduction of LDL-C levels.
Assuntos
Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/terapia , Adolescente , Anticolesterolemiantes/uso terapêutico , Criança , LDL-Colesterol/sangue , Doença da Artéria Coronariana/prevenção & controle , Estudos Transversais , Suplementos Nutricionais , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/sangue , Estilo de Vida , Masculino , Sistema de Registros , Estados Unidos/epidemiologiaRESUMO
Sitosterolemia is a rare atherogenic sterol storage disease with variability in its presentation requiring a high degree of clinical suspicion. We present 8 cases of sitosterolemia from an Amish kindred that, despite a background of decreased genetic and lifestyle variability, still had markedly variable presentations. (Level of Difficulty: Advanced.).
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OBJECTIVE: To identify non-high-density lipoprotein cholesterol (HDL-C) and HDL-C thresholds for pediatric nonfasting lipid screens that are more predictive of the need for lipid-lowering pharmacotherapy and estimate numbers of potentially avoidable fasting lipid panels. STUDY DESIGN: In this retrospective review of children and youths aged 8-21 years presenting for preventive cardiology care, initial lipid results, recommendations for pharmacotherapy, and presence of additional cardiovascular risk factors were noted. Receiver operating characteristic curve analysis calculated threshold lipid values predicting the need for pharmacotherapy and were applied to 2 screening populations. Rates of potentially unnecessary fasting lipid panels were calculated. RESULTS: A non-HDL-C value >156 mg/dL for children with ≥1 cardiovascular risk factors and >199 mg/dL for children without risk factors conferred 95% or greater sensitivity in predicting a recommendation for pharmacotherapy with higher specificity, positive predictive value, and negative predictive value compared with current guidelines. HDL-C was a poor predictor of pharmacotherapy. Application of the current thresholds to screening populations indicated that 38.5%-92.3% of follow-up fasting lipid panels would not result in pharmacotherapy. CONCLUSION: Using higher non-HDL-C and lower HDL-C thresholds could prevent unnecessary follow-up lipid panels and reduce patient anxiety, cost, and time. This could improve compliance with universal pediatric lipid screening for both health care providers and families.
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Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Hipercolesterolemia/diagnóstico , Hipolipemiantes/administração & dosagem , Lipídeos/normas , Adolescente , Fatores Etários , Doenças Cardiovasculares/etiologia , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hipercolesterolemia/complicações , Masculino , Programas de Rastreamento , Valor Preditivo dos Testes , Prevenção Primária/métodos , Padrões de Referência , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) level and lipoprotein(a) [Lp(a)] ≥ 50 mg/dL predict atherosclerotic cardiovascular disease (ASCVD) risk in adults with familial hypercholesterolemia (FH), but their role for children with FH is less clear. OBJECTIVE: This study examined the relationship between elevated Lp(a) and LDL-C levels in a pediatric population with FH and onset of ASCVD in family members. METHODS: Retrospective review of pediatric patients with FH identified LDL-C, Lp(a), and family history of ASCVD. Logistic regression modeling evaluated the association between the child's Lp(a) and peak LDL-C level with earliest age of ASCVD onset in their family. RESULTS: One hundred twenty-nine children from 109 families were identified. Children from families with early-onset ASCVD were 3 times more likely to have high Lp(a) than those with a family history of late-onset ASCVD (OR: 3.77, 95% CI: 1.16-12.25, P = .027) but were not more likely to have highly elevated peak LDL-C (≥190 mg/dL) (OR: 0.45, 95% CI: 0.11-1.80, P = .26). CONCLUSION: Children with FH and family history of early-onset ASCVD were more likely to have Lp(a) ≥50 mg/dL than children with FH and family history of late-onset ASCVD. Family history of early-onset ASCVD was more predictive of a child's Lp(a) level than of a child's peak LDL-C. Measurement of Lp(a) in children with FH may better characterize their cardiovascular risk, particularly when knowledge of family history is limited. Lp(a) testing may also identify children with FH that could benefit from more aggressive management to reduce ASCVD risk.
Assuntos
Aterosclerose/complicações , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/complicações , Lipoproteína(a)/sangue , Linhagem , Adulto , Idade de Início , Aterosclerose/diagnóstico , Criança , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de RiscoRESUMO
OBJECTIVE: To evaluate whether the release of national guidelines, electronic health record (EHR) modifications, and educational initiatives correlated with changes in pediatricians' universal lipid screening practices. STUDY DESIGN: Retrospective review of EHRs in an academic general pediatric practice was performed to measure the prevalence of order placement. A child was "screened" if an order was placed during a well-visit between 9 and 21 years of age. The prevalence of order placement for lipid screens on 22 374 patients from January 2010 to December 2015 was analyzed for date of order and patient age, then compared with timing of guidelines, local educational initiatives, and EHR modifications. Primary study outcome was lipid screening order placement over time. RESULTS: Order placement increased from 8.9% (95% CI 8.3%-9.5%) before any intervention to 50.0% (95% CI 48.8%-51.2%) over the last 12 months of the study period (P < .001). All age groups showed significant increases in order placement. Changes in screening were seen following guideline publications, educational initiatives, and EHR modifications (for all, P < .0001). Order completion was 69.6% (95% CI 68.9%-70.3%). The composite prevalence of screening (order placement multiplied by order completion) was 46.8% over the 6-year study period. CONCLUSIONS: Improved adherence to recommendations for universal lipid screening is possible through educational initiatives and EHR modifications. Inclusion of 12- to 16-year-old adolescents/teenagers as a targeted group for universal screening in addition to recommended age groups improved screening prevalence. Similar efforts could be applicable for implementation of other guidelines.
Assuntos
Lipídeos/sangue , Programas de Rastreamento/métodos , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Criança , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pediatria , Guias de Prática Clínica como Assunto , Prevalência , Estudos Retrospectivos , Adulto JovemRESUMO
Charts of 42 children with familial hypercholesterolemia from a dyslipidemia clinic were reviewed for initial cholesterol screen indication and cascade screening results. Indications were universal screening (8/28 after guideline release, none before), family history (26/42), risk factor (5/42), and other (3/42). Cascade screening identified 63 relatives with unknown familial hypercholesterolemia.
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Hiperlipoproteinemia Tipo II/diagnóstico , Lipídeos/sangue , Programas de Rastreamento/métodos , Adolescente , Instituições de Assistência Ambulatorial , Criança , Feminino , Humanos , Masculino , Encaminhamento e Consulta , Estudos Retrospectivos , Adulto JovemRESUMO
We present a newborn with heterotaxy features, multiple congenital anomalies, truncus arteriosus with long segment tracheal stenosis, and a left pulmonary artery sling. The patient had complete neonatal repair with slide tracheoplasty and repair of the left pulmonary artery sling with anterior translocation of the pulmonary artery. The truncus was repaired with a transventricular ventricular septal defect closure with a patch and right ventricle to pulmonary artery conduit. Complete repair of complex cardiac neonatal lesions with critical tracheal stenosis is feasible and should be the strategy of choice in these complex patients.
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Síndrome de Heterotaxia/cirurgia , Artéria Pulmonar/anormalidades , Estenose Traqueal/cirurgia , Persistência do Tronco Arterial/cirurgia , Síndrome de Heterotaxia/complicações , Síndrome de Heterotaxia/diagnóstico , Humanos , Recém-Nascido , Masculino , Estenose Traqueal/complicações , Estenose Traqueal/diagnóstico , Persistência do Tronco Arterial/complicações , Persistência do Tronco Arterial/diagnósticoRESUMO
BACKGROUND: Mitral valve dysplasia syndrome is a unique form of left-sided heart disease characterized by aortic outflow hypoplasia, dilated left ventricle, dysplastic/incompetent mitral valve, and a restrictive/intact atrial septum. Patients with this constellation of abnormalities have been managed in a variety of ways with overall poor outcomes. METHODS: We performed a retrospective review of all patients with mitral valve dysplasia syndrome to identify fetal echocardiographic markers predictive of outcomes. RESULTS: Mitral valve dysplasia syndrome was identified in 10 fetuses. Fetal left heart dilation and abnormal pulmonary venous flow were associated with increased mortality. Seven fetuses had abnormal pulmonary venous Doppler patterns; 3 had a unique "double-reversal" flow pattern. Severe fetal left heart dilation (left heart/right heart area ratio > 1.5) was present in 5. Prenatal intervention was performed on 3 fetuses: balloon aortic valvuloplasty (n = 2) and balloon atrial septostomy (n = 1). Of the 3, one died in utero and neither survivor underwent a 2-ventricle repair. Five patients required an immediate postnatal intervention to open the atrial septum. The overall mortality was 50%. CONCLUSIONS: Mitral valve dysplasia syndrome is a unique form of congenital heart disease with severe aortic stenosis but normal or enlarged left ventricle secondary to primary mitral valve disease. Increased left heart size and pulmonary vein Doppler patterns are predictive of postnatal outcome. Despite the presence of a dilated left ventricle, postnatal management with staged single ventricle palliation may be the most effective strategy.
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Cardiopatias Congênitas/diagnóstico por imagem , Valva Mitral/anormalidades , Procedimentos Cirúrgicos Cardíacos , Cateterismo , Doenças Fetais/diagnóstico por imagem , Doenças Fetais/patologia , Doenças Fetais/terapia , Coração Fetal/diagnóstico por imagem , Idade Gestacional , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/cirurgia , Septos Cardíacos/patologia , Humanos , Síndrome do Coração Esquerdo Hipoplásico , Lactente , Recém-Nascido , Circulação Pulmonar , Síndrome , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) causes morbidity and mortality in neonates. High-frequency ventilation (HFV), inhaled nitric oxide (iNO), and extracorporeal membrane oxygenation (ECMO) are used when conventional treatment fails. This study aimed to identify echocardiographic predictors of progression to these therapies before clinical deterioration. METHODS: Echocardiographic parameters were compared for survival and need for ECMO, HFV, iNO, and prolonged mechanical ventilation (MV, >or=10 days). RESULTS: Of 63 neonates, 95% survived, with 14% requiring ECMO, 52% requiring HFV, 67% requiring iNO, and 35% requiring MV. The following echocardiographic indices reflecting left ventricular output were decreased in sicker infants: (1) A decreased ascending aortic velocity time integral indicated an increased likelihood of ECMO (p=0.02), iNO (p=0.01), or MV (p=0.05), (2) Shorter transverse aortic arch antegrade ejection time indicated HFV (p<0.01), iNO (p<0.01), and MV (p=0.03), (3) Absent or retrograde transverse aortic diastolic flow correlated with HFV (p=0.01, iNO (p=0.01), and MV (p<0.01). These sicker patients were more likely to have smaller left ventricular end-diastolic areas (p<0.03 for all) and right-to-left atrial shunting (ECMO, HFV, and MV). There were no differences in survival. CONCLUSIONS: Decreased left ventricular size and output correlates with the need for advanced therapies in infants with PPHN. Early identification may allow more effective management and placement of neonates at risk.