title: Cardiac resynchronization therapy improves minute ventilation/carbon dioxide production slope and skeletal muscle capillary density without reversal of skeletal muscle pathology or inflammation.
abstract: OBJECTIVE
  We evaluated the effects of cardiac resynchronization therapy (CRT) on skeletal muscle pathology and inflammation in patients with heart failure.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Cardiology, Stavanger University Hospital, N-4001 Stavanger, Norway. alfil@broadpark.no; laai@sus.no
authors: Alf Inge
authors: AI
authors: Larsen
authors: Sigurd
authors: S
authors: Lindal
authors: Kate
authors: K
authors: Myreng
authors: Christer
authors: C
authors: Ogne
authors: Jan Terje
authors: JT
authors: Kvaløy
authors: Peter Scott
authors: PS
authors: Munk
authors: Pål
authors: P
authors: Aukrust
authors: Arne
authors: A
authors: Yndestad
authors: Kenneth
authors: K
authors: Dickstein
authors: Dennis W T
authors: DW
authors: Nilsen
mesh_terms: D000368:Aged; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D002245:Carbon Dioxide / Q000378:metabolism; D058406:Cardiac Resynchronization Therapy; D005260:Female; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D009220:Myositis / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D010101:Oxygen Consumption; D012123:Pulmonary Ventilation; D016896:Treatment Outcome
chemical_list: D002245:Carbon Dioxide
keywords: CRT; Chronic heart failure; Cytokines; Inflammation; Peak VO2; Skeletal muscle; VE/VCO2 slope