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BACKGROUND: Familial hypercholesterolaemia is a well-known disorder, but clinical diagnoses tend to be delayed. Acute coronary syndrome may occur in childhood. CASE SUMMARY: Our patient, a young boy with homozygous familial hypercholesterolaemia, complained of persistent chest pain at rest and suffered a non-ST-elevation myocardial infarction (NSTEMI). The diagnosis of NSTEMI was made on the basis of his clinical features, dynamic electrocardiogram changes, troponin elevation, and cardiac computed tomography findings. The patient was managed surgically by intrathoracic artery (ITA) bypass graft. During post-operative follow-up, the young patient suffered from angina pectoris from unexpected and exceptional atheroma stenosis on the ITA. DISCUSSION: Familial hypercholesterolaemia needs to be identified quickly in young patients and lipid lowering therapies should be started without delay.
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BACKGROUND: Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention. METHODS: Over a 2-month period, contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. RESULTS: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range, 2-16 years). Comorbidities were present in 28%, including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was <30% in one-third; 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation. Inflammation markers were suggestive of cytokine storm (interleukin-6 median, 135 pg/mL) and macrophage activation (D-dimer median, 5284 ng/mL). Mean BNP (B-type natriuretic peptide) was elevated (5743 pg/mL). Thirty-one of 35 patients (88%) tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. All patients received intravenous immunoglobulin, with adjunctive steroid therapy used in one-third. Left ventricular function was restored in the 25 of 35 of those discharged from the intensive care unit. No patient died, and all patients treated with extracorporeal membrane oxygenation were successfully weaned. CONCLUSIONS: Children may experience an acute cardiac decompensation caused by severe inflammatory state after SARS-CoV-2 infection (multisystem inflammatory syndrome in children). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.
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COVID-19/complicaciones , Insuficiencia Cardíaca/virología , Inflamación/virología , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Adolescente , COVID-19/virología , Niño , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Volumen Sistólico/fisiología , Síndrome de Respuesta Inflamatoria Sistémica/virología , Disfunción Ventricular Izquierda/tratamiento farmacológico , Función Ventricular Izquierda/inmunologíaRESUMEN
PRDM16 (positive regulatory domain 16) is localized in the critical region for cardiomyopathy in patients with deletions of chromosome 1p36, as defined by Gajecka et al., American Journal of Medical Genetics, 2010, 152A, 3074-3083, and encodes a zinc finger transcription factor. We present the first fetal case of left ventricular non-compaction (LVNC) with a PRDM16 variant. The third-trimester obstetric ultrasound revealed a hydropic fetus with hydramnios and expanded hypokinetic heart. After termination of pregnancy, foetopathology showed a eutrophic fetus with isolated cardiomegaly. Endocardial fibroelastosis was associated with non-compaction of the myocardium of the left ventricle. Exome sequencing (ES) identified a de novo unreported p.(Gln353*) heterozygous nonsense variant in PRDM16. ES also identified two rare variants of unknown significance, according to the American College of Medical Genetics and Genomics guidelines, in the titin gene (TTN): a de novo missense p.(Lys14773Asn) variant and a c.33043+5A>G variant inherited from the mother. Along with the PRDM16 de novo probably pathogenic variant, TTN VOUS variants could possibly contribute to the severity and early onset of the cardiac phenotype. Because of the genetic heterogeneity of cardiomyopathies, large panels or even ES could be considered as the main approaches for the molecular diagnosis, particularly in fetal presentations, where multiple hits seem to be common.
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Cardiomiopatías/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Cardiopatías Congénitas/genética , Factores de Transcripción/genética , Adulto , Cardiomiopatías/diagnóstico , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/patología , Femenino , Genes Modificadores/genética , Heterogeneidad Genética , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/patología , Humanos , Recién Nacido , Presentación en Trabajo de Parto , Masculino , Persona de Mediana Edad , Mutación/genética , Linaje , Embarazo , Secuenciación del ExomaRESUMEN
BACKGROUND: Rare genetic variants in TNNI3K encoding troponin-I interacting kinase have been linked to a distinct syndrome consisting primarily of supraventricular tachycardias and variably expressed conduction disturbance and dilated cardiomyopathy in 2 families. OBJECTIVE: The purpose of this study was to identify new genetic variants associated with inherited supraventricular tachycardias, cardiac conduction disease, and cardiomyopathy. METHODS: We conducted next generation sequencing in 3 independent multigenerational families with atrial/junctional tachycardia with or without conduction disturbance, dilated cardiomyopathy, and sudden death. We also assessed the effect of identified variant on protein autophosphorylation. RESULTS: In this study, we uncovered the same ultra-rare genetic variant in TNNI3K (c.2302G>A, p.Glu768Lys), which co-segregated with disease features in all affected individuals (n = 23) from all 3 families. TNNI3K harboring the TNNI3K-p.Glu768Lys variant displayed enhanced kinase activity, in line with expectations from previous mouse studies that demonstrated increased conduction indices and procardiomyopathic effects with increased levels of Tnni3k. CONCLUSION: This study corroborates further the causal link between rare genetic variation in TNNI3K and this distinct complex phenotype, and points to enhanced kinase activity of TNNI3K as the underlying pathobiological mechanism.
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Cardiomiopatía Dilatada/genética , ADN/genética , Sistema de Conducción Cardíaco/fisiopatología , Mutación , Proteínas Serina-Treonina Quinasas/genética , Taquicardia Supraventricular/genética , Adolescente , Western Blotting , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/fisiopatología , Células Cultivadas , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas , Humanos , Imagen por Resonancia Cinemagnética/métodos , Masculino , Linaje , Proteínas Serina-Treonina Quinasas/metabolismo , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatología , Adulto JovenRESUMEN
Autosomal dominant genetic diseases can occur de novo and in the form of somatic mosaicism, which can give rise to a less severe phenotype, and make diagnosis more difficult given the sensitivity limits of the methods used. We report the case of female child with a history of surgery for syndactyly of the hands and feet, who was admitted at 6 years of age to a pediatric intensive care unit following cardiac arrest. The electrocardiogram (ECG) showed a long QT interval that on occasions reached 500 ms. Despite the absence of facial dysmorphism and the presence of normal psychomotor development, a diagnosis of Timothy syndrome was made given the association of syndactyly and the ECG features. Sanger sequencing of the CACNA1C gene, followed by sequencing of the genes KCNQ1, KCNH2, KCNE1, KCNE2, were negative. The subsequent analysis of a panel of genes responsible for hereditary cardiac rhythm disorders using Haloplex technology revealed a recurrent mosaic p.Gly406Arg missense mutation of the CACNA1C gene in 18% of the cells. This mosaicism can explain the negative Sanger analysis and the less complete phenotype in this patient. Given the other cases in the literature, mosaic mutations in Timothy syndrome appear more common than previously thought. This case demonstrates the importance of using next-generation sequencing to identify mosaic mutations when the clinical picture supports a specific mutation that is not identified using conventional testing. © 2016 Wiley Periodicals, Inc.
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Trastorno Autístico/diagnóstico , Trastorno Autístico/genética , Canales de Calcio Tipo L/genética , Estudios de Asociación Genética , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/genética , Mosaicismo , Mutación , Fenotipo , Sindactilia/diagnóstico , Sindactilia/genética , Alelos , Sustitución de Aminoácidos , Niño , Codón , Análisis Mutacional de ADN , Electrocardiografía , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , HumanosAsunto(s)
Anomalías Múltiples/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Discapacidad Intelectual/genética , Fenotipo , Trombocitopenia/genética , Niño , Deleción Cromosómica , Cromosomas Humanos Par 21/genética , Diagnóstico Diferencial , Humanos , Masculino , SíndromeRESUMEN
BACKGROUND: The long-term outcome of repaired aortic coarctation may be complicated by dilatation of the ascending aorta notably in patients with bicuspid aortic valve. Magnetic resonance imaging was used to compare the size of the ascending aorta in patients with bicuspid or tricuspid aortic valve. METHODS: In 50 patients with a repair of aortic coarctation, the size of the ascending aorta was measured in a bicuspid aortic valve group (n=11) and a tricuspid aortic valve group (n=39). The aortic diameter was measured at the level of the sinus of Valsalva and at the widest part of the ascending aorta using magnetic resonance imaging. RESULTS: The mean age of patients at surgical repair was respectively 2.2+/-3.3 years for the bicuspid aortic valve group and 2.5+/-3.5 years for the tricuspid aortic valve group (p=NS) and the mean age at the time of the magnetic resonance imaging was 10.2+/-4.7 years and 9.3+/-5.9 years (p=NS) respectively. A significant difference in the aortic diameter was found between the bicuspid aortic valve group and the tricuspid aortic group both at the level of sinus of Valsalva (34.8+/-8.2 mm, 19.5+/-4.4 mm, respectively, p<0.01) and at the level of the ascending aorta (36.8+/-7.2 mm, 16.9+/-3.4 mm, respectively, p<0.01). CONCLUSIONS: The occurrence of ascending aortic dilatation is significantly associated with the presence of a bicuspid aortic valve. This requires long-term follow-up, which can be effectively performed by magnetic resonance imaging.
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Aorta/patología , Coartación Aórtica/cirugía , Válvula Aórtica/anomalías , Válvula Aórtica/cirugía , Preescolar , Continuidad de la Atención al Paciente , Dilatación Patológica , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Periodo PosoperatorioRESUMEN
BACKGROUND AND AIM OF THE STUDY: Although described in a number of necropsy studies, endocarditis on mitral annular calcification (MAC) has rarely been reported during life. The study aim was to assess the frequency and specific features of bacterial endocarditis complicating MAC. METHODS: Data relating to 62 cases of infective endocarditis of the native mitral valve diagnosed with multiplane transesophageal echocardiography (TEE) over a five-year period were collected prospectively. RESULTS: Among 62 patients, 15 (24%) had vegetations originating from a calcified mitral annulus (group 1), while 47 had classic leaflet endocarditis (group 2). Group 1 patients differed significantly from group 2 patients with regard to: (i) higher incidence of diabetes mellitus and cancers; (ii) initial clinical presentation, with febrile coma or meningoencephalitis in 53% of cases; (iii) echocardiographic features, with significantly greater vegetations, presence of calcium-dense echoes within the vegetation, high frequency of ring abscess, and high frequency of para-annular ventriculoatrial leakage; and (iv) poorer clinical outcome, with 53% in-hospital mortality. CONCLUSION: MAC appears to be an underestimated predisposing factor for a particularly severe type of bacterial endocarditis. The use of multiplane TEE should improve current knowledge of this disease.
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Calcinosis/microbiología , Endocarditis Bacteriana/microbiología , Enfermedades de las Válvulas Cardíacas/microbiología , Válvula Mitral/microbiología , Infecciones Estafilocócicas/microbiología , Infecciones Estreptocócicas/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Calcinosis/diagnóstico por imagen , Calcinosis/epidemiología , Procedimientos Quirúrgicos Cardíacos , Ecocardiografía , Ecocardiografía Transesofágica , Endocarditis Bacteriana/diagnóstico por imagen , Endocarditis Bacteriana/epidemiología , Femenino , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Admisión del Paciente , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Prevalencia , Estudios Prospectivos , Infecciones Estafilocócicas/diagnóstico por imagen , Infecciones Estafilocócicas/epidemiología , Infecciones Estreptocócicas/diagnóstico por imagen , Infecciones Estreptocócicas/epidemiología , Resultado del TratamientoRESUMEN
Aortic root abscess often complicates the course of aortic valve endocarditis. In severe cases, left ventricular-aortic discontinuity may occur, providing challenging technical problems for the surgeon. Moreover, surgical intervention sometimes takes place in a semi-emergency context, and the patches and prosthesis are sutured into friable tissues and subjected to high systemic pressures. Subsequently, paravalvular leaks and prosthesis dehiscence are not uncommon; postoperative false aneurysm of the aortic root is a much more unusual complication. We report one case of right ventricular outflow obstruction that occurred after surgical treatment of an aortic root abscess. Echocardiographic data were useful, but magnetic resonance imaging provided valuable information about the anatomic extent of the cavity. (ECHOCARDIOGRAPHY, Volume 13, January 1996)