Copyright © 2002 by the European Society of Cardiology.
Alveolarcapillary membrane gas conductance: a novel prognostic indicator in chronic heart failure
a Centro Cardiologico, I.R.C.C.S., Centro di Studio Ricerche Cardiovascolari del Consiglio Nazionale delle Ricerche, Istituto di Cardiologia dellUniversità, Milan, Italy
b Istituto di Statistica Medica e Biometria dellUniversità, Milan, Italy
revised May 25, 2001; accepted June 1, 2001
Abstract
Aims Lung dysfunction occurring in chronic heart failure worsens clinical status and exercise performance. The prognostic value of airway and alveolar function measurements in chronic heart failure has not been explored. We aimed to evaluate the prognostic value of lung function tests in a population of patients with stable chronic heart failure.
Methods and Results One hundred and six stable chronic heart failure patients (whose left ventricular ejection fraction averaged 33±1%) underwent echocardiography, metabolic stress testing, assessment of pulmonary function at rest (by spirometry), of alveolar diffusing capacity (DLco) (with carbon monoxide technique) and of its membrane (DM) and capillary blood volume (Vc) components. Prognostic relevance of pulmonary variables was assessed by the KaplanMeier approach with log-rank testing and by Cox regression analysis. Cut-off values of lung parameters were based on the 33rd and 66th centiles. Seventeen patients died for cardiac reasons. Non-survivors compared to survivors showed lower forced expiratory volume in 1s (2·1±0·1 vs 2·4±0·1l;P <0·01), forced vital capacity (2·6±0·1 vs 2·9±0·1l;P <0·01), maximal voluntary ventilation (80·7±2·5vs 95·4±2·7l; P<0·01), DLco (16·5±1·1 vs 19·3±0·6ml.min1.mmHg1;P <0·01) and DM (25·1±1·8 vs 31·9±1·5ml.min1.mmHg1;P <0·01). They also exhibited a smaller peak VO2 (14·6±0·7 vs 15·9±0·6ml.min1.kg1;P <0·05) and a steeper VE/VCO2 slope (45·0±1·7 vs 41·9±1·5;P <0·01). Multivariate analysis revealed that DM was the only independent predictor of cardiac death. Cases at high risk for adverse outcome were identified by a DM<24·7ml.min1.mmHg1. Patients receiving ACE-inhibitors presented with a higher DM (32·1±1·7 vs 27·9±1·7ml.min1.mmHg1,P <0·05) as well as a better Cox estimated survival rate.
Conclusions Impaired DM is a powerful independent predictor of worse prognosis in stable chronic heart failure and may be considered an additional index of disease severity, as well as a specific therapeutic target.
Key Words: Heart failure, pulmonary function, survival
f1 Correspondence: Marco Guazzi, MD, PhD, FACC, Istituto di Cardiologia dell'Università, Centro Cardiologico, Via Parea, 4, 20138 Milano, Italy.
References
- 2000 Heart and stroke statistical update, Dallas, American Heart Association, 1999
- Cohn JN. The management of chronic heart failure. N Engl J Med. 1996;335:490498
[Free Full Text] - Lucas C, Johnson W, Hamilton MA, Fonarow GC, Woo MA, Flavell CM, Creaser JA, Stevenson LW. Freedom from congestion predicts good survival despite previous class IV symptoms of heart failure. Am Heart J. 2000;140:840847[CrossRef][Web of Science][Medline]
- Mancini DM. Pulmonary factors limiting exercise capacity in patients with heart failure. Prog Cardiov Dis. 1996;6:347370
- Kraemer MD, Kubo SH, Rector TS, Brunsvold N, Bank AJ. Pulmonary and peripheral vascular factors are important determinants of peak exercise oxygen uptake in patients with heart failure. J Am Coll Cardiol. 1993;22:641648
- Sullivan MJ, Higgimbotham MB, Cobb FR. Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite hemodynamic and pulmonary abnormalities. Circulation. 1988;77:552559
[Abstract/Free Full Text] - West JB, Mathieu-Costello O. Structure, strength, failure and remodelling of the pulmonary gas barrier. Ann Rev Physiol. 1999;61:543572[CrossRef][Web of Science][Medline]
- Tsukimoto K, Mathieu-Costello O, West JB. Pulmonary microvascular permeability. Responses to high vascular pressure after induction of pacing-induced heart failure in dogs. Circ Res. 1995;77:317325
[Abstract/Free Full Text] - MacGrowan GA, Janosko K, Cecchetti A, Murali S. Exercise-related ventilatory abnormalities and survival in congestive heart failure. Am J Cardiol. 1997;79:12641266[CrossRef][Web of Science][Medline]
- Chua TP, Ponikowski P, Harrington D. Clinical correlates and prognostic significance of the ventilatory response to exercise in chronic heart failure. J Am Coll Cardiol. 1997;29:15851590[Abstract]
- Robbins M, Francis G, Pashkow MD. Ventilatory and heart rate response to exercise. Better predictors of heart rate mortality than peak oxygen consumption. Circulation. 1999;100:24112417
[Abstract/Free Full Text] - Pardaens K, Cleemput JV, Vanhaeke J, Fagard RH. Peak oxygen uptake better predicts outcome than submaximal respiratory data in heart transplant candidates. Circulation. 2000;101:11521157
[Abstract/Free Full Text] - Puri S, Baker L, Dutka DP, Oakley C, Hughes JMB, Cleland JGF. Reduced alveolar-capillary membrane diffusing capacity in chronic heart failure. Its pathophysiological relevance and relationship to exercise performance. Circulation. 1995;91:27692774
[Abstract/Free Full Text] - Guazzi M, Marenzi GC, Alimento M, Contini M, Agostoni PG. Improvement of alveolar-capillary membrane diffusing capacity with enalapril in chronic heart failure and counteracting effect of aspirin. Circulation. 1997;95:19301936
[Abstract/Free Full Text] - Beaver WL, Wasserman K, Whipp BJ. A new method for detecting the anaerobic threshold by gas exchange. J Appl Physiol. 1986;60:20202027
[Abstract/Free Full Text] - Knudson RJ, Lebowitz MD, Holberg CJ, Burrow B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Resp Dis. 1983;127:725734[Web of Science][Medline]
- Roughton FJW, Forster FE. Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in human lung, with special reference to true diffusing capacity of blood in the lung capillary. J Appl Physiol. 1957;11:290302
[Abstract/Free Full Text] - Cotes JE. Lung function. Oxford: Blackwell Scientific Publications; 1979. p. 23949
- Guazzi M, Agostoni PG. ACE-inhibition restores the diffusing capacity for carbon monoxide in chronic heart failure patients by improving the molecular diffusion across the alveolar capillary membrane. Clin Sci. 1999;96:1722[Medline]
- Kannel WB, Hubert H, Lew FA. Vital capacity as a predictor of cardiovascular disease: the Framingham Study. Am Heart J. 1983;105:311315[CrossRef][Web of Science][Medline]
- Kannel WB, D'Agostino RB, Silbershatz H. Use of vital capacity for cardiac failure risk estimation in persons with coronary disease and left ventricular hypertrophy. Am J Cardiol. 1996;77:11551158[CrossRef][Web of Science][Medline]
- Anonik PK, Olds NB, McNamara DM. Forced vital capacity identifies heart failure patients with decompensated hemodynamics and poor one-year outcome (Abstr). Circulation. 1999;98:I865
- Guazzi M. Alveolar-capillary membrane dysfunction in chronic heart failure: pathophysiology and therapeutic implications. Clin Sci. 2000;98:633641[Medline]
- Collins J, Clark T, Brown D. Airway function in healthy subjects and patients with left heart failure. Cli Sci Mol Med. 1975;49:217218
- Light R, George R. Serial pulmonary function in patients with acute heart failure. Arch Intern Med. 1983;143:429433
[Abstract/Free Full Text] - Hosenpud JD, Stibolt TA, Atval K, Shelley D. Abnormal pulmonary function specifically related to congestive heart failure; comparison of patients before and after cardiac transplantation. Am J Med. 1990;88:493496[CrossRef][Web of Science][Medline]
- Lin MC, Rockman HA, Chien KR. Heart and lung disease in engineered mice: technological miniaturization combined with the power of molecular genetics makes the mouse a model animal for understanding human cardiovascular and pulmonary disease. Nat Med. 1995;1:749751[CrossRef][Web of Science][Medline]
- Matthay MA, Folkesson HG, Verkman AS. Salt and water transport across alveolar and distal airway epithelia in the adult lung. Am J Physiol. 1996;270:L487L503
- Hocking DC, Phillips PG, Ferro TJ, Johnson A. Mechanism of pulmonary edema induced by tumor necrosis factor-
. Circ Res. 1990;67:6877[Abstract/Free Full Text] - Puri S, Dutka DP, Baker BL, Hughes JM, Cleland JGF. Acute saline infusion reduces alveolar-capillary membrane conductance and increases airflow obstruction in patients with left ventricular dysfunction. Circulation. 1999;99:11901196
[Abstract/Free Full Text] - Guazzi M, Agostoni PG, Bussotti M, Guazzi MD. Impeded alveolar-capillary gas transfer with saline infusion in heart failure. Hypertension. 1999;34:12021207
[Abstract/Free Full Text] - Agostoni PG, Guazzi M, Bussotti M, Grazi M, Palermo P, Marenzi GC. Lack of improvement of diffusing lung capacity following fluid withdrawal by ultrafiltration in chronic heart failure. J Am Coll Cardiol. 2000;36:16001604
[Abstract/Free Full Text] - Mettauer B, Lampert E, Charloux A. Lung membrane diffusing capacity, heart failure and heart transplantation. Am J Cardiol. 1999;83:6267[CrossRef][Web of Science][Medline]
- Guazzi M, Melzi G, Agostoni PG. Comparison of changes in respiratory function and exercise oxygen uptake with losartan versus enalapril in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 1997;80:15721576[CrossRef][Web of Science][Medline]
- Guazzi M, Agostoni PG, Guazzi MD. Modulation of alveolar-capillary sodium handling as a mechanism of protection of gas transfer by enalapril, and not by losartan in chronic heart failure. J Am Coll Cardiol. 2001;37:398406
[Abstract/Free Full Text] - Knudson RJ, Kaltenborn WT, Burrows B. The effects of cigarette smoking and smoking cessation on the carbon monoxide diffusing capacity of the lung in asymptomatic subjects. Am Rev Resp Dis. 1989;140:645651[Web of Science][Medline]
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