title: Determinants of ventilatory efficiency in heart failure: the role of right ventricular performance and pulmonary vascular tone.
abstract: BACKGROUND
  Ventilatory efficiency, right ventricular (RV) function, and secondary pulmonary hypertension are each prognostic indicators in patients with heart failure due to left ventricular systolic dysfunction, but the relationships among these variables have not been comprehensively investigated. In this study, we hypothesized that inefficient ventilation during exercise, as defined by an abnormally steep relationship between ventilation and carbon dioxide output (Ve/Vco(2) slope), may be a marker of secondary pulmonary hypertension and RV dysfunction in heart failure.
  
  
  RESULTS
  A cohort of patients with systolic heart failure (mean+/-SD age, 58+/-13 years; left ventricular ejection fraction, 0.27+/-0.05; peak oxygen uptake, 11.2+/-3.2 mL kg(-1) min(-1)) underwent incremental cardiopulmonary exercise testing with simultaneous hemodynamic monitoring and first-pass radionuclide ventriculography before and after 12 weeks of treatment with sildenafil, a selective pulmonary vasodilator, or placebo. Ve/Vco(2) slope was positively related to rest and exercise pulmonary vascular resistance (R=0.39 and R=0.60, respectively) and rest pulmonary capillary wedge pressure (R=0.49, P<0.005 for all) and weakly indirectly related to peak exercise RV ejection fraction (R=-0.29, P=0.03). Over the 12-week study period, Ve/Vco(2) slope fell 8+/-3% (P=0.02) with sildenafil and was unchanged with placebo. Changes in Ve/Vco(2) slope correlated with changes in exercise pulmonary vascular resistance (R=0.69, P<0.001) and rest and exercise RV ejection fraction (R=-0.58 and -0.40, respectively, both P<0.05).
  
  
  CONCLUSIONS
  In patients with systolic heart failure and secondary pulmonary hypertension, ventilatory efficiency is closely related to RV function and pulmonary vascular tone during exercise.
authors.affiliation: Cardiology Division, Department of Medicine, and Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. glewis@partners.org
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Lewis
authors.forename: Ravi V
authors.initials: RV
authors.lastname: Shah
authors.forename: Paul P
authors.initials: PP
authors.lastname: Pappagianopolas
authors.forename: David M
authors.initials: DM
authors.lastname: Systrom
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Semigran
mesh_terms: D000368:Aged; D002245:Carbon Dioxide; D015331:Cohort Studies; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009129:Muscle Tonus; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D010879:Piperazines / Q000627:therapeutic use; D011652:Pulmonary Circulation; D011687:Purines / Q000627:therapeutic use; D012119:Respiration; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use; D014655:Vascular Resistance; D014665:Vasodilator Agents / Q000627:therapeutic use; D016278:Ventricular Function, Right; D015646:Ventriculography, First-Pass
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D002245:Carbon Dioxide; D000068677:Sildenafil Citrate