RESUMEN
Although Friedreich ataxia (FA) is associated with cardiomyopathy, the severity and evolution of cardiac disease is poorly understood. To identify factors predicting cardiomyopathy in FA, we assessed echocardiograms from a large heterogenous cohort and their relation to disease traits. The most recent echocardiograms from 173 subjects with FA were analyzed in a core laboratory to determine their relation to disease duration, subject age, age of onset, functional disability score, and GAA repeat length. Mean age of the cohort was 19.7 years, mean age of disease onset was 10.6 years, and mean shorter GAA length was 681 repeats. Echocardiograms collectively illustrated systolic dysfunction, diastolic dysfunction, and hypertrophy. Measurements of hypertrophy correlated moderately with each other (r = 0.39 to 0.79) but not with measurements of diastolic dysfunction (r <0.35). Diastolic measurements correlated poorly with each other, although 26% of the cohort had multiple diastolic abnormalities. The most common diastolic dysfunction classification was pseudonormalization. Classification of diastolic dysfunction was predicted by GAA repeat length but not by age or gender. Ejection fraction was below normal in 20% of the cohort. In linear regression analysis, increasing age predicted decreasing ejection fraction. Functional disability score, a measurement of neurologic ability, did not predict any echocardiographic measurements. In conclusion, hypertrophy and diastolic and systolic dysfunctions occur in FA and are substantially independent; diastolic dysfunction is the most common abnormality with most patients having an assigned diastolic dysfunction class of pseudonormalization.
Asunto(s)
Ecocardiografía Doppler/métodos , Ataxia de Friedreich/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Contracción Miocárdica/fisiología , Volumen Sistólico , Disfunción Ventricular Izquierda/diagnóstico por imagen , Adolescente , Niño , Diástole , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Ataxia de Friedreich/complicaciones , Ataxia de Friedreich/fisiopatología , Humanos , Hipertrofia Ventricular Izquierda/complicaciones , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Pronóstico , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Although cardiac dysfunction is widely accepted as the most common cause of mortality in Friedreich ataxia (FRDA), no studies have evaluated this since the advent of specific clinical and genetic diagnostic criteria. METHODS: We performed a retrospective study of FRDA patients to determine cause of death followed by a case-control analysis comparing characteristics of deceased patients with living, age- and sex-matched FRDA controls. RESULTS: Causes of death were cardiac dysfunction (59%), probable cardiac dysfunction (3.3%), non-cardiac (27.9%) or unknown (9.8%). Compared to non-cardiac deaths, cardiac deaths occurred earlier in the disease course (median 29 vs. 17years respectively). Congestive heart failure and arrhythmia were common causes of cardiac-related death. Compared to living, matched FRDA controls, deceased patients had longer triplet repeat lengths and higher rates of arrhythmia and dilated cardiomyopathy. The presence of hypertrophic cardiomyopathy did not differ between deceased and living patients. CONCLUSION: Cardiac dysfunction was the most frequent cause of death (59%), most commonly from congestive heart failure or arrhythmia. Arrhythmia and dilated cardiomyopathy were significantly more common in deceased patients compared to matched FRDA controls, while in contrast, the presence of cardiac hypertrophy did not differ. More research is needed to establish the clinical significance of hypertrophy in FRDA.
Asunto(s)
Ataxia de Friedreich/mortalidad , Cardiopatías/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/genética , Arritmias Cardíacas/mortalidad , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/mortalidad , Estudios de Casos y Controles , Estudios de Cohortes , Comorbilidad , Femenino , Ataxia de Friedreich/genética , Cardiopatías/diagnóstico , Cardiopatías/genética , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: Friedreich ataxia (FRDA) is an autosomal recessive, neurodegenerative disease. Recent medical advances have improved the average life expectancy, and as such, many female patients are contemplating pregnancy. However, little research exists exploring the medical or psychosocial complications that arise from pregnancy with this disease. STUDY DESIGN: In this study, we retrospectively examined 31 women with FRDA who had 65 pregnancies, resulting in 56 live offspring. RESULTS: FRDA did not appear to increase the risk of spontaneous abortion, preeclampsia, or preterm birth. Despite the sensory and proprioceptive loss that occurs in FRDA, nearly four fifths of births were vaginal. Of babies, 94.4% were discharged home with their mothers. Equal numbers of women reported that pregnancy made their disease symptoms worse, better, or unchanged. CONCLUSION: This study demonstrates that women with FRDA can have uncomplicated pregnancies that do not uniformly complicate disease symptomatology.
Asunto(s)
Ataxia de Friedreich/epidemiología , Ataxia de Friedreich/psicología , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/psicología , Aborto Espontáneo/epidemiología , Adulto , Puntaje de Apgar , Peso al Nacer , Parto Obstétrico/estadística & datos numéricos , Femenino , Humanos , Recién Nacido , Tiempo de Internación/estadística & datos numéricos , Nacimiento Vivo/epidemiología , Embarazo , Nacimiento Prematuro/epidemiología , Estudios Retrospectivos , Nacimiento a TérminoRESUMEN
The use of health-related quality of life scales as outcome measures in clinical trials is increasing. Although such measures have been validated in adults with Friedreich ataxia, they have not been studied in children with this disorder. The health-related quality of life of children with Friedreich ataxia was assessed using the PedsQL 4.0 Generic Core Module and Multidimensional Fatigue Scale. The scores from the Friedreich ataxia cohort were compared to those of control groups (children without a chronic disease). Minimal missing responses support the feasibility of using the PedsQL 4.0 in the Friedreich ataxia population. The scales demonstrated internal consistency, and concordance was observed between child and proxy scores. Children with Friedreich ataxia and their proxies reported lower health-related quality of life than did controls in the Core and Fatigue scales. A modest relationship was seen between markers of disease status and health-related quality of life, providing support for the idea that children with Friedreich ataxia have a lower health-related quality of life than those without a chronic disease. Additional studies are needed to examine the relationship between health-related quality of life and disease markers and to further establish the validity of the PedsQL 4.0 in this population.