Asunto(s)
Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca/terapia , Mitocondrias Musculares/metabolismo , Músculo Esquelético/metabolismo , ARN Mensajero/metabolismo , Factores de Transcripción/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Anciano , Biomarcadores/sangre , Bloqueo de Rama/metabolismo , Enfermedad Crónica , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIMS: We evaluated the effects of cardiac resynchronization therapy (CRT) on skeletal muscle pathology and inflammation in patients with heart failure. METHODS AND RESULTS: Stable patients (n = 21, 14 males, mean age 70 ± 7 years) with symptomatic heart failure (mean left ventricular ejection fraction 24 ± 6%) and an indication for CRT were included. Ergospirometry, skeletal muscle open biopsy, and blood sampling were performed prior to implantation and after 6 months of CRT. After CRT there was a reduction in both left ventricular end-diastolic diameter (LVEDD; 6.8 ± 0.8 vs. 6.3 ± 0.7 cm, P < 0.001) and native QRS duration (D) minus biventricular paced QRSD (172.9 ± 23 vs. 136.3 ± 23 ms, P ≤ 0.001). These changes were associated with an increase in peak slope oxygen uptake (consumption) (VO2) (13.3 ± 2.2 vs. 14.5 ± 2.6 mL/kg/min, P = 0.07) and an improvement in the minute ventilation/carbon dioxide production slope (VE/VCO2) slope (41.6 ± 7.4 vs. 39.1 ± 5.6, P = 0.012). There were no statistically significant changes in levels of pro-inflammatory cytokines, in mediators of mitochondrial biosynthesis or skeletal muscle pathology, except for an increase in skeletal muscle capillary density (4.5 ± 2.4 vs. 7.7 ± 3.3%, P = 0.002). Both the reduction of QRS duration and the increase in peak VO2 correlated significantly with the change in mitochondrial density (r = 0.57, P = 0.008 and r = 0.54, P = 0.027, respectively). CONCLUSION: Cardiac resynchronization therapy, with improved functional status and reduced LVEDD resulted in increased peak VO2, improvement in VE/VCO2 slope and capillary density in skeletal muscle, with no reduction in systemic pro-inflammatory cytokines, increase in intramuscular levels of mediators of mitochondrial biosynthesis or improvement in skeletal muscle ultrastructure per se. ClinicalTrials.gov Identifier: NCT01019915.
