RESUMEN
The hexanucleotide repeat expansion in intron 1 of the C9orf72 gene causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In addition to the effects of the pathogenic expansion, a role of intermediate-length alleles has been suggested in ALS, corticobasal degeneration and Parkinson's disease. Due to the rarity of intermediate-length alleles with over 20 repeats and the geographical variability in their frequency, large studies that account for population stratification are needed to elucidate their effects. To this aim, we used repeat-primed PCR and confirmatory PCR assays to determine the C9orf72 repeat allele lengths in 705 ALS patients and 3958 controls from Finland. After exclusion of expansion carriers (25.5% of the ALS patients and 0.2% of the controls), we compared the frequency of intermediate-length allele carriers of 525 ALS cases and 3950 controls using several intermediate-length allele thresholds (7-45, 17-45, 21-45, 24-45 and 24-30). The carriership of an intermediate-length allele did not associate with ALS (Fisher's test, all p ≥ 0.15) nor was there any association with survival (p ≥ 0.33), when we divided our control group into three age groups (18-65, 66-84 and 85-105 years). Carriership of two intermediate-length alleles was associated with ALS, when the longer allele was ≥ 17 repeats (p = 0.002, OR 5.32 95% CI 2.02-14.05) or ≥ 21 repeats (p = 0.00016, OR 15.21 95% CI 3.79-61.0). Our results show that intermediate-length alleles are a risk factor of ALS when present in both alleles, whereas carrying just one intermediate-length allele was not associated with ALS or survival.
Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Proteína C9orf72/genética , Expansión de las Repeticiones de ADN/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Femenino , Finlandia , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
OBJECTIVES: We sought to study the indications, long-term occurrence, and predictors of permanent pacemaker implantation (PPI) after isolated surgical aortic valve replacement with bioprostheses. METHODS: The CAREAVR study included 704 patients (385 females, 54.7%) without a preoperative PPI (mean ± standard deviation age 75 ± 7 years) undergoing isolated surgical aortic valve replacement at 4 Finnish hospitals between 2002 and 2014. Data were extracted from electronic patient records. RESULTS: The follow-up was median 4.7 years (range 1 day to 12.3 years). Altogether 56 patients received PPI postoperatively, with the median 507 days from the operation (range 6 days to 10.0 years). The PPI indications were atrioventricular block (31 patients, 55%) and sick sinus syndrome (21 patients, 37.5%). For 4 patients, the PPI indication remained unknown. A competing risks regression analysis (Fine-Gray method), adjusted with age, sex, diabetes, coronary artery disease, preoperative atrial fibrillation (AF), left ventricular ejection fraction, New York Heart Association class, AF at discharge and urgency of operation, was used to assess risk factors for PPI. Only AF at discharge (subdistribution hazard ratio 4.34, 95% confidence interval 2.34-8.03) was a predictor for a PPI. CONCLUSIONS: Though atrioventricular block is the major indication for PPI after surgical aortic valve replacement, >30% of PPIs are implanted due to sick sinus syndrome during both short-term follow-up and long-term follow-up. Postoperative AF versus sinus rhythm conveys >4-fold risk of PPI. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02626871.
Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Fibrilación Atrial/prevención & control , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas/métodos , Prótesis Valvulares Cardíacas , Marcapaso Artificial , Anciano , Estenosis de la Válvula Aórtica/fisiopatología , Fibrilación Atrial/fisiopatología , Femenino , Humanos , Masculino , Periodo Posoperatorio , Factores de Riesgo , Volumen Sistólico , Factores de Tiempo , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Preoperative permanent atrial fibrillation (AF) is associated with impaired outcome after surgical aortic valve replacement (SAVR). The impact of preoperative paroxysmal AF, however, has remained elusive. PURPOSE: We assessed the impact of preoperative paroxysmal AF on outcome in patients undergoing SAVR with bioprosthesis. METHODS: A total of 666 patients undergoing isolated AVR with a bioprosthesis were included. Survival data was obtained from the national registry Statistics Finland. Patients were divided into three groups according to the preoperative rhythm: sinus rhythm (n = 502), paroxysmal AF (n = 90), and permanent AF (n = 74). RESULTS: Patients in the sinus rhythm and paroxysmal AF groups did not differ with respect to age (P = .484), gender (P = .402) or CHA2 DS2 -VASc score (P = .333). At 12-month follow-up, AF was present in 6.2% of sinus rhythm patients and in 42.4% of paroxysmal AF patients (P < .001). During follow-up, incidence of fatal strokes in the paroxysmal AF group was higher compared to sinus rhythm group (1.9 vs 0.4 per 100 patient-years, HR 4.4 95% Cl 1.8-11.0, P = .001). Cardiovascular mortality was higher in the paroxysmal AF group than in the sinus rhythm group (5.0 vs 3.0 per 100 patient-years, HR 1.70 95% CI 1.05-2.76, P = .03) and equal to patients in the permanent AF (5.0 per 100 patient-years). CONCLUSION: Patients undergoing SAVR with bioprosthesis and history of paroxysmal AF had higher risk of developing permanent AF, cardiovascular mortality and incidence of fatal strokes compared to patients with preoperative sinus rhythm. Life-long anticoagulation should be considered in patients with a history of preoperative paroxysmal AF.