title: Reduced peripheral skeletal muscle mass and abnormal reflex physiology in chronic heart failure.
abstract: BACKGROUND
  The muscle hypothesis implicates abnormalities in peripheral muscle as a source for the stimulus to the symptoms and reflex abnormalities seen in chronic heart failure (CHF). We investigated the relationship between skeletal muscle mass (with dual-energy x-ray absorptiometry) and activation of the ergoreflex (a peripheral reflex originating in skeletal muscle sensitive to products of muscle work) in CHF patients and whether this rapport is affected by the progression of the syndrome.
  
  
  RESULTS
  We assessed 107 consecutive CHF patients (mean age, 61.9+/-10.9 years; 95% male; 25 cachectics) and 24 age-matched normal subjects (mean age, 59.0+/-11.1 years; 91% male). Compared with normal subjects, patients had a higher ergoreflex (in ventilation, 6.2+/-.6.1 versus 0.6+/-0.6 L/min; P<0.0001) and a reduction in muscle mass (51.9+/-10.0 versus 60.3+/-8.8 kg; P<0.001). The ergoreflex was particularly overactive in cachectics (P<0.05), accompanied by marked muscle mass depletion (P<0.0005). In CHF, ergoreceptor hyperresponsiveness in both the arm and leg correlated with reduced muscle mass, abnormal indexes of exercise tolerance (peak V(O2), V(E)/V(CO2) slope), ejection fraction, and NYHA functional class (P<0.0001). In the cachectic population, the ventilatory response from ergoreflex to arm exercise was strongly inversely correlated with arm (r=-0.65), leg (r=-0.64), and total (r=-0.61) lean tissues (P<0.001 for all). Multivariate analysis showed that these relationships were independent of NYHA class, peak V(O2), and V(E)/V(CO2) slope.
  
  
  CONCLUSIONS
  Depleted peripheral muscle mass is associated with ergoreflex overactivity and exercise limitation in CHF, particularly in cachectic patients. The systemic activation of the muscle reflex system in CHF may reflect progression and deterioration of the clinical syndrome.
authors.affiliation: Heart Failure Unit, Cardiology, Guglielmo da Saliceto Polichirurgico Hospital, Cantone del Cristo, Piacenza, 29100, Italy. m.piepoli@imperial.ac.uk
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Piepoli
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kaczmarek
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
authors.forename: L Ceri
authors.initials: LC
authors.lastname: Davies
authors.forename: Mathias
authors.initials: M
authors.lastname: Rauchhaus
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Jankowska
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Alessandro
authors.initials: A
authors.lastname: Capucci
authors.forename: Waldemar
authors.initials: W
authors.lastname: Banasiak
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
mesh_terms: D000368:Aged; D001823:Body Composition; D002908:Chronic Disease; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000033:anatomy & histology* / Q000502:physiology / Q000503:physiopathology*; D012016:Reference Values; D012018:Reflex / Q000502:physiology*; D016277:Ventricular Function, Left