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BACKGROUND: A significant percentage of patients with congenital heart disease surviving into adulthood will develop arrhythmias. These arrhythmias are associated with an increased risk of adverse events and death. We aimed to assess arrhythmia prevalence, risk factors, and associated health care usage in a large national cohort of patients with adult congenital heart disease. METHODS AND RESULTS: Adults with a documented diagnosis of congenital heart disease, insured by Clalit and Maccabi health services between January 2007 and December 2011, were included. We assessed the associations between arrhythmia and subsequent hospitalization rates and death with mixed negative binomial and Cox proportional hazard models, respectively. Among 11 653 patients with adult congenital heart disease (median age, 47 years [interquartile range, 31-62]), 8.7% had a tachyarrhythmia at baseline, 1.5% had a conduction disturbance, and 0.5% had both. Among those without a baseline arrhythmia, 9.2% developed tachyarrhythmias, 0.9% developed a conduction disturbance, and 0.3% developed both during the study period. Compared with no arrhythmia (reference group), arrhythmia in the previous 6 months was associated with a higher multivariable adjusted hospitalization rate, 1.33-fold higher than the rate of the reference group (95% CI, 1.00-1.76) for ventricular arrhythmia, 1.27-fold higher (95% CI, 1.17-1.38) for atrial arrhythmias, and 1.33-fold higher (95% CI, 1.04-1.71) for atrioventricular block. Atrial tachyarrhythmias were associated with an adjusted mortality hazard ratio (HR) of 1.65 (95% CI, 1.44-2.94), and ventricular tachyarrhythmias with a >2-fold increase in mortality risk (HR, 2.06 [95% CI, 1.44-2.94]). CONCLUSIONS: Arrhythmias are significant comorbidities in the adult congenital heart disease population and have a significant impact on health care usage and survival.
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Arritmias Cardíacas , Cardiopatías Congénitas , Humanos , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/mortalidad , Femenino , Masculino , Adulto , Persona de Mediana Edad , Arritmias Cardíacas/epidemiología , Factores de Riesgo , Prevalencia , Hospitalización/estadística & datos numéricos , Estados Unidos/epidemiología , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
Background: Determining the pathogenesis of sudden cardiac arrest (SCA) in children is crucial for its management and prognosis. Our aim is to analyze the role of broad genetic testing in the prevention, diagnosis, and prognosis of SCA in Children. Methods: ECG, 12-lead holter, exercise testing, cardiac imaging, familial study, and genetic testing were used to study 29 families, in whom a child experienced SCA. Results: After a thorough clinical and genetic evaluation a positive diagnosis was reached in 24/29 (83%) families. Inherited channelopathies (long QT syndrome and catecholaminergic polymorphic ventricular tachycardia) were the most prevalent 20/29 (69%) diagnosis, followed by cardiomyopathy 3/29 (10%). Broad genetic testing was positive in 17/24 (71%) cases. Using the Mann-Whitney test, we found that genetic testing (effect size = 0.625, p = 0.003), ECG (effect size = 0.61, p = 0.009), and exercise test (effect size = 0.63, p = 0.047) had the highest yield in reaching the final diagnosis. Genetic testing was the only positive test available for five (17%) families. Among 155 family members evaluated through cascade screening, 73 (47%) had a positive clinical evaluation and 64 (41%) carried a pathologic mutation. During 6 ± 4.8 years of follow-up, 58% of the survived children experienced an arrhythmic event. Of nine family members who had an ICD implant for primary prevention, four experienced appropriate ICD shock. Conclusions: The major causes of SCA among children are genetic etiology, and genetic testing has a high yield. Family screening has an additional role in both the diagnosis and preventing of SCA.
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Danon disease is a rare x-linked dominant multisystemic disorder with a clinical triad of severe cardiomyopathy, skeletal myopathy, and intellectual disability. It is caused by defects in the lysosome-associated membrane protein-2 (LAMP2) gene. Numerous different mutations in the LAMP2 protein have been described. Danon disease is typically lethal by the mid-twenties in male patients due to cardiomyopathy and heart failure. Female patients usually present with milder and variable symptoms. This report describes a 42-year-old father and his 3-year-old daughter presenting with mild manifestations of the disease. The father has normal intellectual development and normal physical activity. At the age of 13, he was diagnosed with mild ventricular pre-excitation known as Wolf-Parkinson-White syndrome (WPWs), very mild and mostly asymptomatic cardiomyopathy and left ventricular hypertrophy, and at about the age of 25 presented with visual impairment due to cone-rod dystrophy. His daughter showed normal development and very mild asymptomatic electrocardiographic WPWs abnormalities with left mild ventricular hypertrophy. Genetic testing revealed an Xq24 microdeletion encompassing the entire LAMP2 gene. Relevant literature was reviewed as a reference for the etiology, diagnosis, treatment and case management.
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Distrofias de Conos y Bastones , Enfermedad por Depósito de Glucógeno de Tipo IIb , Insuficiencia Cardíaca , Femenino , Masculino , Humanos , Enfermedad por Depósito de Glucógeno de Tipo IIb/diagnóstico , Enfermedad por Depósito de Glucógeno de Tipo IIb/genética , Eliminación de Gen , Genes Reguladores , Proteína 2 de la Membrana Asociada a los Lisosomas/genéticaRESUMEN
OBJECTIVES: When cardiac muscle damage occurs, cardiac troponins are released to blood and their detection is used as a marker in clinical setting. The prognostic value of the quantitative levels of blood troponin I in cases of myocarditis and myopericarditis is unclear. The aim of this study was to analyse whether troponin quantitative blood levels can be correlated with the course of hospitalisation and prognosis. METHODS: Retrospective data was collected from all consecutive patients aged ≤30 hospitalised with a diagnosis of acute myocarditis or acute myopericarditis in our health Care Campus between the years 2010-2016. RESULTS: Ninety-three patients with myocarditis and myopericarditis were identified. Higher peak troponin levels correlated with longer hospitalisation times in the cardiac or paediatric wards (p = 0.03, Pearson correlation: r -0.23), and median troponin level at admission correlated with longer overall hospitalisation (p = 0.026, Pearson correlation: r = 0.23). Patients admitted to ICU, received oral cardiac supportive therapy or that were discharged with cardiac drugs had higher median troponin compared to patients who were not but this was not statistically significant. A small group of patients that needed intravenous cardiac support had significantly lower median peak troponin levels (n = 4, 0.375ng/ml, p = 0.048). Only two patients needed extracorporeal membrane oxygenation support, and one died. The small number of patients precludes statistical analysis. CONCLUSION: Higher troponin levels correlated significantly with longer hospitalisation, lower troponin values correlated with intravenous cardiac support, while other variables related to the severity of disease could not be significantly related to higher troponin levels.
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Miocarditis , Pericarditis , Humanos , Niño , Adolescente , Adulto Joven , Troponina I , Miocarditis/diagnóstico , Estudios Retrospectivos , Pericarditis/diagnóstico , Antiarrítmicos , Cardiotónicos , Índice de Severidad de la EnfermedadRESUMEN
Jatrogenic communication between left ventricle and right atrium, known as Gerbode type ventricular septal defect (GVSD) may be observed after different surgical interventions. We present a case of iatrogenic GVSD following complex cardiac surgery including septal myectomy combined with mitral and aortic valve replacement, which was successfully closed percutanously by Occlutech septal occluder.
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Defectos del Tabique Interventricular , Prótesis Valvulares Cardíacas , Dispositivo Oclusor Septal , Humanos , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Cateterismo Cardíaco/efectos adversos , Defectos del Tabique Interventricular/diagnóstico por imagen , Defectos del Tabique Interventricular/etiología , Defectos del Tabique Interventricular/cirugía , Enfermedad Iatrogénica , Resultado del TratamientoRESUMEN
BACKGROUND: Heart rate variability (HRV) has been suggested as an indicator of capacity to adapt effectively to physiological or environmental challenges and of physical and psychological health in old age. AIMS: The study assessed levels of high-frequency HRV (HF-HRV) among older adults in relation to positive and negative affect and the mediating role of positive and negative affect in the association between coping resources (perceived social support and sense of mastery) and HF-HRV. METHOD: Participants were 187 men and women in three assisted-living residences who were independent in activities of daily living (93.4% participation rate). The participants completed sense of mastery, multidimensional scale of perceived social support, and positive and negative affect questionnaires. HF-HRV was derived from electrocardiography data measured by a Holter monitoring device for 15 minutes. RESULTS: The empirical model showed good fit indices indicating that higher HF-HRV was associated with lower negative affect, and negative affect mediated the association between perceived social support and HF-HRV. In addition, perceived social support and sense of mastery were associated with higher positive affect and lower negative affect. CONCLUSIONS: Although this was a cross-sectional study, it suggests that HF-HRV may be a link between affect and health in old age. It also suggests the importance of identification and intervention with older adults and their support systems to reduce negative affect.
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Actividades Cotidianas , Envejecimiento , Adaptación Psicológica , Anciano , Estudios Transversales , Femenino , Frecuencia Cardíaca/fisiología , Humanos , MasculinoRESUMEN
Background Several studies have examined hospitalizations among patients with adult congenital heart disease (ACHD). Few investigated other services or utilization patterns. Our aim was to study service utilization patterns and predictors among patients with ACHD. Methods and Results We identified 11 653 patients with ACHD aged ≥18 years (median, 47 years), through electronic records of 2 large Israeli healthcare providers (2007-2011). The association between patient, disease, and sociogeographic characteristics and healthcare resource utilization were modeled as recurrent events accounting for the competing death risk. Patients with ACHD had high healthcare utilization rates compared with the general population. The highest standardized service utilization ratios (SSRs) were found among patients with complex congenital heart disease including primary care visits (SSR, 1.53; 95% CI, 1.47-1.58), cardiology outpatient visits (SSR, 5.17; 95% CI, 4.69-5.64), hospitalizations (SSR, 6.68; 95% CI, 5.82-7.54), and days in hospital (SSR, 15.37; 95% CI, 14.61-16.12). Adjusted resource utilization hazard increased with increasing lesion complexity. Hazard ratios (HRs) for complex versus simple disease were: primary care (HR, 1.14; 95% CI, 1.06-1.23); cardiology outpatient visits (HR, 1.40; 95% CI, 1.24-1.59); emergency department visits (HR, 1.19; 95% CI, 1.02-1.39); and hospitalizations (HR, 1.75; 95% CI, 1.49-2.05). Effects attenuated with age for cardiology outpatient visits and hospitalizations and increased for emergency department visits. Female sex, geographic periphery, and ethnic minority were associated with more primary care visits, and female sex (HR versus men, 0.89 [95% CI, 0.84-0.94]) and periphery (HR, 0.72 [95% CI, 0.58-0.90] for very peripheral versus very central) were associated with fewer cardiology visits. Arab minority patients also had high hospitalization rates compared with the majority group of Jewish or other patients. Conclusions Healthcare utilization rates were high among patients with ACHD. Female sex, geographic periphery, and ethnicity were associated with less optimal service utilization patterns. Further research should examine strategies to optimize service utilization in these groups.
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Servicio de Cardiología en Hospital/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Cardiopatías Congénitas , Aceptación de la Atención de Salud , Atención Primaria de Salud , Atención Ambulatoria/métodos , Atención Ambulatoria/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Etnicidad , Femenino , Necesidades y Demandas de Servicios de Salud , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/terapia , Hospitalización/estadística & datos numéricos , Humanos , Israel/epidemiología , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud/etnología , Aceptación de la Atención de Salud/estadística & datos numéricos , Atención Primaria de Salud/métodos , Atención Primaria de Salud/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Factores SexualesRESUMEN
OBJECTIVE: This study presents data from the admission trial to show the feasibility, safety and effectiveness of the Nit-Occlud® Lê VSD in the treatment of perimembranous ventricular septal defects with an aneurysmal configuration and a diameter up to 8 mm. BACKGROUND: The majority of ventricular septal defects (VSD) are still closed surgically, while a less invasive transcatheter treatment by closure devices is available. Device-based closure is reported to be associated with the risk of complete atrio-ventricular block, especially with double-disc devices in perimembranous defects. METHODS: In six tertiary centers in Germany and Israel, an interventional closure of a periembranous VSD was attempted in 88 patients using the Nit-Occlud® Lê VSD. RESULTS: The interventional VSD closure was performed in 85 patients. Patients had a median age of 8.0 (2-65) years and a median body weight of 26.7 (10-109) kg. A complete closure of the defects was achieved in 85.4% 2 weeks after device implantation, in 88.9% after three months and in 98.6% at the 5-year follow-up. There was no incidence of death during the study nor did any patient suffer of permanent atrio-ventricular block of higher degree. Serious adverse events, by definition, are potentially life-threatening or require surgery to correct, while major serious events require medical or transcatheter intervention to correct. The study results exhibit a serious adverse event rate of 3.5% (3/85 patients) and a major adverse event rate of 5.9% (5/85 patients). CONCLUSION: The Nit-Occlud® Lê VSD coil offers the possibility of an effective and safe approach in patients with aneurysmal perimembranous ventricular septal defects.
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Cateterismo Cardíaco/métodos , Procedimientos Quirúrgicos Cardíacos/métodos , Defectos del Tabique Interventricular/cirugía , Dispositivo Oclusor Septal , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Heart failure is a major health and economic challenge in both developing and developed countries. Despite advances in pharmacological and device therapies for patients with a reduced left ventricular ejection fraction (LVEF) and heart failure, their quality of life and exercise capacity are often persistently impaired, morbidity and mortality remain high and the health economic and societal costs are considerable. For patients with heart failure and preserved LVEF, diuretic management has an essential role for controlling congestion and symptoms, even if no intervention has convincingly shown to reduce morbidity or mortality. Remote monitoring might improve care delivery and clinical outcomes for patients regardless of LVEF. A great variety of innovative remote monitoring technologies and algorithms are being introduced, including patient self-managed testing, wearable devices, technologies either integrated into established clinically indicated therapeutic devices, such as pacemakers and defibrillators, or as stand-alone are in development providing the promise of further improvements in service delivery and clinical outcomes. In this article, we will discuss unmet needs in the management of patients with heart failure, how remote monitoring might contribute to future solutions, and provide an overview of current and novel remote monitoring technologies.
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Insuficiencia Cardíaca , Calidad de Vida , Humanos , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: The patent foramen ovale (PFO) occluder is a bulky metallic device. Its impact on the normal blood flow at the superior vena cava-right atrial (SVC-RA) junction is not clear. METHODS: We examined SVC-RA junction flow-pattern using pulsed-wave (PW) ultrasound Doppler in 21 patients (4 male, aged 52.7 ± 9 years) who underwent PFO device closure 4-120 months previously, in comparison with 21 age- and sex-matched controls (4 male, aged 51 ± 8.5 years) with structurally normal hearts. RESULTS: Mean systolic flow velocity at the SVC-RA junction was 60 ± 11 cm/s in the PFO closure group and 64 ± 17 cm/s in the control group (P = 0.27). Mean diastolic blood flow velocity at the SVC-RA junction in those groups was 30 ± 8 and 35 ± 9 cm/s, respectively (P = 0.1).The mean systolic wave duration was 439 ± 52 ms in the PFO closure group and 422 ± 67 ms in the control group (P = 0.4). The mean diastolic wave duration was 320 ± 75 and 277 ± 88 ms, respectively (P = 0.12). CONCLUSION: The study results show that transcatheter PFO closure does not affect the normal blood flow at the SVC-RA junction.
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Velocidad del Flujo Sanguíneo/fisiología , Foramen Oval Permeable/cirugía , Atrios Cardíacos/diagnóstico por imagen , Ultrasonografía Doppler de Pulso , Vena Cava Superior/diagnóstico por imagen , Estudios de Casos y Controles , Diástole , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dispositivo Oclusor Septal , SístoleRESUMEN
Congenital long QT syndrome (LQTS) is a cardiac channelopathy that leads to the prolongation of the QT interval. This prolongation can lead to ventricular tachyarrhythmia, syncope, and sudden cardiac death. There are various types of LQTS. Treatment of LQT1 and LQT2 is mainly based on antiadrenergic therapy. LQT3, on the other hand, is a result of a mutation of the SCN5A gene, which encodes the sodium channels. In this type, patients are sensitive to vagal stimuli and episodes tend to occur at rest. Sodium channel blocking compounds, such as ranolazine, mexiletine, and flecainide, have been found to be effective in selective mutations.In this case report, we report the case of a child with congenital LQT3 (V411M) who presented first with sudden cardiac death and three weeks later with an implantable cardioverter defibrillator storm. Knowing the specific mutation and understanding the mechanism at the molecular level through an in vitro study yielded a clinically meaningful result. The patient's arrhythmia burden was totally eliminated following successful treatment with flecainide.
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ADN/genética , Electrocardiografía , Flecainida/uso terapéutico , Síndrome de QT Prolongado/tratamiento farmacológico , Mutación , Canal de Sodio Activado por Voltaje NAV1.5/genética , Niño , Análisis Mutacional de ADN , Femenino , Humanos , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/genética , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , Bloqueadores del Canal de Sodio Activado por Voltaje/uso terapéuticoRESUMEN
BACKGROUND: The significance of depression/anxiety among ACHD patients in terms of health care utilization is unknown and data on the association with mortality are scarce. METHODS: Analyses comprised 8334 ACHD patients, ageâ¯≥â¯18â¯years, insured by a large healthcare organization (2007-2011). Depression/anxiety were determined by diagnoses and treatments recorded in the organization database. Adjusted utilization relative rates (RRs) were estimated with negative binomial models and mortality hazard ratios (HRs) with the Cox proportional hazard model. RESULTS: ACHD patients with depression/anxiety (Nâ¯=â¯2950, 35%) were more likely to be older (mean⯱â¯SD: 54⯱â¯17 vs. 45⯱â¯18â¯years), women (61% vs. 45%), and have comorbidities than counterparts without depression/anxiety. Following multivariable adjustment, patients with depression/anxiety had more primary care and cardiology clinic visits, more emergency department visits and more hospitalizations. RRs (95% confidence interval) were: 1.31 (1.27-1.35); 1.07 (1.01-1.13); 1.60 (1.46-1.77); and 1.18 (1.08-1.29) respectively, for diagnosis before the study period, and 1.36 (1.31-1.42); 1.22 (1.14-1.30); 1.43 (1.24-1.60) and 1.47 (1.33-1.64), respectively, for diagnosis during the study. Stratifying by age, the highest adjusted primary care and cardiology visit RRs were found among 18-24â¯years old patients and the lowest among patients ≥65â¯years. Between 2007 and 2017, 905 patients died. Depression/anxiety were associated with increased mortality risk with adjusted HRs: 1.10 (95% CI: 0.94-1.29) for past diagnosis and 1.40 (1.17-1.67) for study period depression/anxiety diagnosis. CONCLUSIONS: Depression/anxiety in ACHD patients is associated with increased health-care utilization and a higher risk of death. The efficacy of addressing patients' psychosocial needs in optimizing health-care utilization and improving prognosis needs further evaluation.
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Ansiedad/mortalidad , Depresión/mortalidad , Cardiopatías Congénitas/mortalidad , Aceptación de la Atención de Salud , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/diagnóstico , Ansiedad/psicología , Estudios de Cohortes , Depresión/diagnóstico , Depresión/psicología , Femenino , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/psicología , Humanos , Israel/epidemiología , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Aceptación de la Atención de Salud/psicologíaRESUMEN
Mutations in SCO2 are among the most common causes of COX deficiency, resulting in reduced mitochondrial oxidative ATP production capacity, often leading to hypertrophic cardiomyopathy (HCM). To date, none of the recent pertaining reports provide deep understanding of the SCO2 disease pathophysiology. To investigate the cardiac pathology of the disease, we were the first to generate induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) from SCO2-mutated patients. For iPSC generation, we reprogrammed skin fibroblasts from two SCO2 patients and healthy controls. The first patient was a compound heterozygote to the common E140K mutation, and the second was homozygote for the less common G193S mutation. iPSC were differentiated into cardiomyocytes through embryoid body (EB) formation. To test the hypothesis that the SCO2 mutation is associated with mitochondrial abnormalities, and intracellular Ca2+ -overload resulting in functional derangements and arrhythmias, we investigated in SCO2-mutated iPSC-CMs (compared to control cardiomyocytes): (i) the ultrastructural changes; (ii) the inotropic responsiveness to ß-adrenergic stimulation, increased [Ca2+ ]o and angiotensin-II (AT-II); and (iii) the Beat Rate Variability (BRV) characteristics. In support of the hypothesis, we found in the mutated iPSC-CMs major ultrastructural abnormalities and markedly attenuated response to the inotropic interventions and caffeine, as well as delayed afterdepolarizations (DADs) and increased BRV, suggesting impaired SR Ca2+ handling due to attenuated SERCA activity caused by ATP shortage. Our novel results show that iPSC-CMs are useful for investigating the pathophysiological mechanisms underlying the SCO2 mutation syndrome.
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Cardiomiopatía Hipertrófica/patología , Proteínas Portadoras/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Proteínas Mitocondriales/metabolismo , Miocitos Cardíacos/metabolismo , Potenciales de Acción/efectos de los fármacos , Adulto , Arritmias Cardíacas/patología , Cafeína/farmacología , Cardiomiopatía Hipertrófica/fisiopatología , Proteínas Portadoras/genética , Diferenciación Celular , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Células Madre Pluripotentes Inducidas/ultraestructura , Isoproterenol/farmacología , Masculino , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Proteínas Mitocondriales/genética , Modelos Biológicos , Chaperonas Moleculares , Mutación/genética , Contracción Miocárdica/efectos de los fármacos , Miocitos Cardíacos/ultraestructuraRESUMEN
BACKGROUND: The closure of an atrial septal defect is procedure that is frequently performed in both adults and children. Currently, the most commonly used devices are the Amplatzer® and Occlutech® Figulla® atrial septal occluders. Studies conducted in adults have shown that these devices all have similar performance efficiency for the closure of secundum atrial septal defects. No study to date has examined their performance in the pediatric population. OBJECTIVES: To evaluate and compare the performance of Amplatzer® and Occlutech® Figulla® atrial septal occluders in the pediatric population. METHODS: A consecutive retrospective study of exclusively pediatric patients who underwent percutaneous closure of atrial septal defect with these devices was conducted at our institute. RESULTS: The study comprised 110 children, 50 in the Amplatzer® device group and 60 in the Occlutech® Figulla® device group. The groups had similar demographic and defect characteristics, except for defect size per transesophageal echocardiography (TEE), which was 2.1 mm larger in the Amplatzer® device group (P = 0.02). No adverse events were recorded in either of the study groups. Complete defect closure at 12 months follow-up (procedural success) was achieved in all but one of the patients in the Amplatzer® group and all but two in the Figulla® group (P = 1). The residual shunt rates of fenestrated defects were similar in the two groups. CONCLUSIONS: For children with an isolated secundum atrial septal defect, percutaneous closure is equally safe and effective with either Amplatzer® or Occlutech® Figulla® devices.
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Defectos del Tabique Interatrial/terapia , Dispositivo Oclusor Septal , Cateterismo Cardíaco , Niño , Ecocardiografía Transesofágica , Defectos del Tabique Interatrial/diagnóstico por imagen , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Dilated cardiomyopathy (DCM) is a life-threatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab Christian infants, aged 4-30 months from four families, were diagnosed with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3. A homozygous sequence variation creating a premature stop codon at PPP1R13L encoding the iASPP protein was identified in three infants and in the mother of the other two. Patients' fibroblasts and PPP1R13L-knocked down human fibroblasts presented higher expression levels of pro-inflammatory cytokine genes in response to lipopolysaccharide, as well as Ppp1r13l-knocked down murine cardiomyocytes and hearts of Ppp1r13l-deficient mice. The hypersensitivity to lipopolysaccharide was NF-κB-dependent, and its inducible binding activity to promoters of pro-inflammatory cytokine genes was elevated in patients' fibroblasts. RNA sequencing of Ppp1r13l-knocked down murine cardiomyocytes and of hearts derived from different stages of DCM development in Ppp1r13l-deficient mice revealed the crucial role of iASPP in dampening cardiac inflammatory response. Our results determined PPP1R13L as the gene underlying a novel autosomal-recessive cardio-cutaneous syndrome in humans and strongly suggest that the fatal DCM during infancy is a consequence of failure to regulate transcriptional pathways necessary for tuning cardiac threshold response to common inflammatory stressors.
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Codón sin Sentido , Péptidos y Proteínas de Señalización Intracelular/genética , Síndrome LEOPARD/genética , Síndrome LEOPARD/patología , Proteínas Represoras/genética , Animales , Células Cultivadas , Preescolar , Citocinas/metabolismo , Femenino , Fibroblastos/metabolismo , Técnicas de Silenciamiento del Gen , Humanos , Lactante , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Noqueados , Miocitos Cardíacos/metabolismoRESUMEN
BACKGROUND: The Occlutech Figulla ASD device series (OFSO) shows an improved device design for interventional ASD closure, larger follow-up series are missing. METHODS: We retrospectively reviewed the feasibility, safety, implantation properties, results, and follow-up of ASD closure using Occlutech devices over a 5 year period by establishing a multi-institutional collaborative result registry with 16 contributing centers from 11 countries (IRFACODE). RESULTS: In 1315 patients of all age groups (female 66.9%), successful (98%) ASD closure was performed (mean age 28.9 years, weight 52 kg, height 148.6 cm). Of the defects, 47.9% showed no or only a deficient aortic rim; in 11.9%, there was more than one defect; a septum aneurysm was present in 21.5%; and the mean implanted device size was 20.5 mm. Immediate closure was achieved in 78.6%, at discharge in 83.1%, and 96.4% and 97.3% at 6 and 12 months follow-up, respectively. During a mean follow-up of 2.7 years (in total 3597 patient years), significant complications were minimal (total = 8, <1%) with secondary device embolizations in five and AV-blocks in three patients. No erosion or death was reported. CONCLUSION: ASD closure using OFSO is feasible in a large variety of patients, safe with only a minimal risk of severe side effects and especially without any aortic erosions despite a large percentage of large and complicated defects. © 2016 Wiley Periodicals, Inc.
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Cateterismo Cardíaco/instrumentación , Defectos del Tabique Interatrial/terapia , Dispositivo Oclusor Septal , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Asia , Cateterismo Cardíaco/efectos adversos , Niño , Preescolar , Europa (Continente) , Estudios de Factibilidad , Femenino , Defectos del Tabique Interatrial/diagnóstico por imagen , Humanos , Lactante , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
UNLABELLED: Haemangiomas represent the most common tumour of infancy. Although most cases are cutaneous benign lesions, multiple skin haemangiomas are associated with visceral involvement, especially of the liver. Hepatic haemangiomatosis may be complicated by high-output cardiac failure due to high-flow arteriovenous connections within the lesions. Different therapeutic strategies for treating haemangiomatosis causing heart failure include medical, surgical and interventional modalities. This study aimed to review the treatment options, discuss their benefits and flaws and propose a practical therapeutic approach for this medical situation. CONCLUSION: Our approach incorporates heart failure medications, dietary support and propranolol as first-line treatment, while corticosteroids, vincristine, percutaneous intervention and surgery are reserved for refractory cases.
Asunto(s)
Insuficiencia Cardíaca/etiología , Hemangioma/complicaciones , Neoplasias Hepáticas/complicaciones , Neoplasias Cutáneas/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Hemangioma/terapia , Humanos , Lactante , Neoplasias Hepáticas/terapia , Neoplasias Cutáneas/terapiaRESUMEN
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia characterized by syncope and sudden death occurring during exercise or acute emotion. CPVT is caused by abnormal intracellular Ca(2+) handling resulting from mutations in the RyR2 or CASQ2 genes. Because CASQ2 and RyR2 are involved in different aspects of the excitation-contraction coupling process, we hypothesized that these mutations are associated with different functional and intracellular Ca(²+) abnormalities. To test the hypothesis we generated induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CM) from CPVT1 and CPVT2 patients carrying the RyR2(R420Q) and CASQ2(D307H) mutations, respectively, and investigated in CPVT1 and CPVT2 iPSC-CM (compared to control): (i) The ultrastructural features; (ii) the effects of isoproterenol, caffeine and ryanodine on the [Ca(2+) ]i transient characteristics. Our major findings were: (i) Ultrastructurally, CASQ2 and RyR2 mutated cardiomyocytes were less developed than control cardiomyocytes. (ii) While in control iPSC-CM isoproterenol caused positive inotropic and lusitropic effects, in the mutated cardiomyocytes isoproterenol was either ineffective, caused arrhythmias, or markedly increased diastolic [Ca(2+) ]i . Importantly, positive inotropic and lusitropic effects were not induced in mutated cardiomyocytes. (iii) The effects of caffeine and ryanodine in mutated cardiomyocytes differed from control cardiomyocytes. Our results show that iPSC-CM are useful for investigating the similarities/differences in the pathophysiological consequences of RyR2 versus CASQ2 mutations underlying CPVT1 and CPVT2 syndromes.
Asunto(s)
Calsecuestrina/genética , Células Madre Pluripotentes Inducidas/patología , Mutación/genética , Miocitos Cardíacos/patología , Canal Liberador de Calcio Receptor de Rianodina/genética , Taquicardia Ventricular/genética , Taquicardia Ventricular/patología , Secuencia de Bases , Cafeína/farmacología , Señalización del Calcio/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Técnicas de Genotipaje , Humanos , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/ultraestructura , Isoproterenol/farmacología , Datos de Secuencia Molecular , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/ultraestructura , Retículo Sarcoplasmático/efectos de los fármacos , Retículo Sarcoplasmático/metabolismo , Retículo Sarcoplasmático/ultraestructuraRESUMEN
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but highly malignant inherited arrhythmic disorder. Although a standardized exercise stress test (ST) is the most reliable way to diagnose CPVT, in 30% only single ventricular premature beats (VPCs) were recorded. OBJECTIVE: To evaluate whether electrocardiographic characteristics of VPCs during ST distinguish patients with CPVT from healthy subjects. METHODS: Electrocardiographic characteristics of VPCs during ST in 16 calsequestrin-2 (CASQ2) mutation carriers CPVT patients were compared with that in 36 healthy subjects. RESULTS: CPVT patients had more VPCs (31 ± 14 vs 3 ± 4, P < 0.0001), longer QRS duration (139 ± 18 ms vs 121 ± 21, P = 0.004), and coupling interval (CI; 476 ± 58 ms vs 355 ± 61 ms, P < 0.0001). The most sensitive characteristics for CPVT were >10 VPCs/test (100% sensitivity, 100% negative predictive value [NPV]), left bundle branch block (LBBB) pattern with inferior axis (88% sensitivity, 94% NPV), and CI longer than 400 ms (88% sensitivity, 94% NPV). Bigeminy or trigeminy or LBBB pattern with inferior axis was most specific for CPVT at 100% (100% positive predictive value PPV, 92% NPV). First VPC during the recovery period and VPC recording more than 1 minute during the recovery period were most specific for healthy subjects (100% specificity, 100% PPV). In multivariate analysis, QRS duration >120 ms (odds ratio 4.2, 95% confidence interval 1-17.6, P = 0.04) and first VPC at ≥10 mets (odds ratio 9.1, 95% confidence interval 2.01-41.1, P = 0.004) each predicted the presence of CPVT. CONCLUSIONS: Several electrocardiographic criteria can help distinguish VPCs originating from CPVT compared with healthy subjects.