Published online before print March 30, 2009, doi: 10.1161/CIRCHEARTFAILURE.108.819607
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Original Articles |
Circulating Plasma Surfactant Protein Type B as Biological Marker of Alveolar-Capillary Barrier Damage in Chronic Heart Failure
From the Centro Cardiologico Monzino-IRCCS (D.M., M. Brioschi, C.B., P.P., M.C., A.A., M. Bussotti, E.T., G.C., C.F., P.A.), Istituto di Cardiologia, Università di Milano, Milan, Italy; Unità Operativa Complessa di Cardiologia, Azienda Ospedaliera Sant’Andrea (D.M.), Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche, Policlinico Umberto I (S.S.), Università degli Studi di Roma "La Sapienza," Italy; Swiss Cardiovascular Center Bern (J.P.S.), Cardiovascular Prevention and Rehabilitation, Bern University Hospital and University of Bern, Bern, Switzerland; Department of Pharmacological Science (E.T.), University of Milan, Milan, Italy; and Division of Pulmonary and Critical Care Medicine (A.P.), University of Washington, Seattle, Wash.
Correspondence to Piergiuseppe Agostoni, Centro Cardiologico Monzino, IRCCS, Istituto di Cardiologia, Università di Milano, via Parea 4, 20138 Milan, Italy. E-mail piergiuseppe.agostoni{at}unimi.it
Received September 5, 2008; accepted February 27, 2009.
Background— Surfactant protein type B (SPB) is needed for alveolar gas exchange. SPB is increased in the plasma of patients with heart failure (HF), with a concentration that is higher when HF severity is highest. The aim of this study was to evaluate the relationship between plasma SPB and both alveolar-capillary diffusion at rest and ventilation versus carbon dioxide production during exercise.
Methods and Results— Eighty patients with chronic HF and 20 healthy controls were evaluated consecutively, but the required quality for procedures was only reached by 71 patients with HF and 19 healthy controls. Each subject underwent pulmonary function measurements, including lung diffusion for carbon monoxide and membrane diffusion capacity, and maximal cardiopulmonary exercise test. Plasma SPB was measured by immunoblotting. In patients with HF, SPB values were higher (4.5 [11.1] versus 1.6 [2.9], P=0.0006, median and 25th to 75th interquartile), whereas lung diffusion for carbon monoxide (19.7±4.5 versus 24.6±6.8 mL/mm Hg per min, P<0.0001, mean±SD) and membrane diffusion capacity (28.9±7.4 versus 38.7±14.8, P<0.0001) were lower. Peak oxygen consumption and ventilation/carbon dioxide production slope were 16.2±4.3 versus 26.8±6.2 mL/kg per min (P<0.0001) and 29.7±5.9 and 24.5±3.2 (P<0.0001) in HF and controls, respectively. In the HF population, univariate analysis showed a significant relationship between plasma SPB and lung diffusion for carbon monoxide, membrane diffusion capacity, peak oxygen consumption, and ventilation/carbon dioxide production slope (P<0.0001 for all). On multivariable logistic regression analysis, membrane diffusion capacity (β, –0.54; SE, 0.018; P<0.0001), peak oxygen consumption (β, –0.53; SE, 0.036; P=0.004), and ventilation/carbon dioxide production slope (β, 0.25; SE, 0.026; P=0.034) were independently associated with SPB.
Conclusion— Circulating plasma SPB levels are related to alveolar gas diffusion, overall exercise performance, and efficiency of ventilation showing a link between alveolar-capillary barrier damage, gas exchange abnormalities, and exercise performance in HF.
Key Words: chronic heart failure • surfactant protein B • lung diffusion • cardiopulmonary exercise test • alveolar-capillary barrier damage