Percent emphysema, airflow obstruction, and impaired left ventricular filling.

BACKGROUND Very severe chronic obstructive pulmonary disease causes cor pulmonale with elevated pulmonary vascular resistance and secondary reductions in left ventricular filling, stroke volume, and cardiac output. We hypothesized that emphysema, as detected on computed tomography (CT), and airflow obstruction are inversely related to left ventricular end-diastolic volume, stroke volume, and cardiac output among persons without very severe lung disease. METHODS We measured left ventricular structure and function with the use of magnetic resonance imaging in 2816 persons who were 45 to 84 years of age. The extent of emphysema (expressed as percent emphysema) was defined as the percentage of voxels below -910 Hounsfield units in the lung windows on cardiac computed tomographic scans. Spirometry was performed according to American Thoracic Society guidelines. Generalized additive models were used to test for threshold effects. RESULTS Of the study participants, 13% were current smokers, 38% were former smokers, and 49% had never smoked. A 10-point increase in percent emphysema was linearly related to reductions in left ventricular end-diastolic volume (-4.1 ml; 95% confidence interval [CI], -3.3 to -4.9; P<0.001), stroke volume (-2.7 ml; 95% CI, -2.2 to -3.3; P<0.001), and cardiac output (-0.19 liters per minute; 95% CI, -0.14 to -0.23; P<0.001). These associations were of greater magnitude among current smokers than among former smokers and those who had never smoked. The extent of airflow obstruction was similarly associated with left ventricular structure and function, and smoking status had similar modifying effects on these associations. Percent emphysema and airflow obstruction were not associated with the left ventricular ejection fraction. CONCLUSIONS In a population-based study, a greater extent of emphysema on CT scanning and more severe airflow obstruction were linearly related to impaired left ventricular filling, reduced stroke volume, and lower cardiac output without changes in the ejection fraction.

[1]  J. Bristow,et al.  Hemodynamics of cor pulmonale. , 1966, Progress in cardiovascular diseases.

[2]  A. Jemal,et al.  Trends in the leading causes of death in the United States, 1970-2002. , 2005, JAMA.

[3]  Michael A. Brooks,et al.  Reproducibility and validity of lung density measures from cardiac CT Scans--The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study. , 2009, Academic radiology.

[4]  G W Dean,et al.  Gravity-independent inequality in pulmonary blood flow in humans. , 1987, Journal of applied physiology.

[5]  J. Marcus,et al.  Early changes of cardiac structure and function in COPD patients with mild hypoxemia. , 2005, Chest.

[6]  H. Mal,et al.  Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation. , 2005, Chest.

[7]  M. Ciurzyński,et al.  Chronic and acute effects of smoking on left and right ventricular relaxation in young healthy smokers. , 2007, Chest.

[8]  Anthony P Reeves,et al.  Impaired flow-mediated dilation is associated with low pulmonary function and emphysema in ex-smokers: the Emphysema and Cancer Action Project (EMCAP) Study. , 2007, American journal of respiratory and critical care medicine.

[9]  C. Rusconi,et al.  Pulmonary function tests in patients with congestive heart failure: effects of medical therapy. , 1993, Cardiology.

[10]  W. MacNee,et al.  Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper , 2004, European Respiratory Journal.

[11]  D Ros,et al.  Pulmonary vascular abnormalities and ventilation-perfusion relationships in mild chronic obstructive pulmonary disease. , 1994, American journal of respiratory and critical care medicine.

[12]  R. Kronmal,et al.  Inflammatory markers and longitudinal lung function decline in the elderly. , 2008, American journal of epidemiology.

[13]  R. Matran,et al.  Bronchial hyperresponsiveness to methacholine in patients with impaired left ventricular function. , 1989, The New England journal of medicine.

[14]  A. Rendas,et al.  [The repercussions of pulmonary congestion on ventilatory volumes, capacities and flows]. , 1994, Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology.

[15]  R W Parkey,et al.  Estimation of human myocardial mass with MR imaging. , 1988, Radiology.

[16]  R. Kronmal,et al.  Multi-Ethnic Study of Atherosclerosis: objectives and design. , 2002, American journal of epidemiology.

[17]  B. Burrows,et al.  Patterns of cardiovascular dysfunction in chronic obstructive lung disease. , 1972, The New England journal of medicine.

[18]  V. Peinado,et al.  Endothelial dysfunction in pulmonary arteries of patients with mild COPD. , 1998, American journal of physiology. Lung cellular and molecular physiology.

[19]  A. Boussuges,et al.  Left atrial and ventricular filling in chronic obstructive pulmonary disease. An echocardiographic and Doppler study. , 2000, American journal of respiratory and critical care medicine.

[20]  J. Hankinson,et al.  Standardisation of spirometry , 2005, European Respiratory Journal.

[21]  L. Cudkowicz Pulmonary emphysema. , 1967, The Nova Scotia medical bulletin.

[22]  E. Weitzenblum CHRONIC COR PULMONALE , 2003, Heart.

[23]  P. Macklem Circulatory effects of expiratory flow-limited exercise, dynamic hyperinflation and expiratory muscle pressure , 2006, European Respiratory Review.

[24]  R. Glenny,et al.  Gravity is a minor determinant of pulmonary blood flow distribution. , 1991, Journal of applied physiology.

[25]  H. Schelbert,et al.  Noninvasive assessment of left ventricular performance in patients with chronic obstructive pulmonary disease. , 1977, Chest.

[26]  I. Petrache,et al.  Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice , 2005, Nature Medicine.

[27]  W. MacNee,et al.  Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease. Part One. , 1994, American journal of respiratory and critical care medicine.

[28]  J L Hankinson,et al.  Spirometric reference values from a sample of the general U.S. population. , 1999, American journal of respiratory and critical care medicine.

[29]  Nico Westerhof,et al.  Impaired left ventricular filling due to right-to-left ventricular interaction in patients with pulmonary arterial hypertension. , 2006, American journal of physiology. Heart and circulatory physiology.

[30]  R. Detrano,et al.  Calcified coronary artery plaque measurement with cardiac CT in population-based studies: standardized protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study. , 2005, Radiology.

[31]  Fishman Ap State of the art: chronic cor pulmonale. , 1976 .

[32]  A. B. Weisse,et al.  Left Ventricular Function, Metabolism, and Blood Flow in Chronic Cor Pulmonale , 1973, Circulation.

[33]  Eric A. Hoffman,et al.  Atlas-driven lung lobe segmentation in volumetric X-ray CT images , 2006, IEEE Transactions on Medical Imaging.

[34]  Shing M. Lee,et al.  Hemodynamic characterization of patients with severe emphysema. , 2002, American journal of respiratory and critical care medicine.

[35]  V. Peinado,et al.  Pulmonary hypertension in chronic obstructive pulmonary disease , 2003, European Respiratory Journal.

[36]  T. Similowski,et al.  Pulmonary blood flow distribution in stage 1 chronic obstructive pulmonary disease. , 2000, American journal of respiratory and critical care medicine.

[37]  R. Upton,et al.  Reduced intrathoracic blood volume and left and right ventricular dimensions in patients with severe emphysema: an MRI study. , 2007, Chest.

[38]  L. Montuenga,et al.  Tumour-associated macrophages in nonsmall cell lung cancer: the role of interleukin-10 , 2007, European Respiratory Journal.

[39]  A. Buda,et al.  Effect of intrathoracic pressure on left ventricular performance. , 1979, The New England journal of medicine.

[40]  R W Parkey,et al.  In vivo measurement of myocardial mass using nuclear magnetic resonance imaging. , 1986, Journal of the American College of Cardiology.

[41]  J. Hankinson,et al.  Performance of American Thoracic Society-recommended spirometry reference values in a multiethnic sample of adults: the multi-ethnic study of atherosclerosis (MESA) lung study. , 2010, Chest.

[42]  Milan Sonka,et al.  Integrated system for CT-based assessment of parenchymal lung disease , 2002, Proceedings IEEE International Symposium on Biomedical Imaging.

[43]  Eric A. Hoffman,et al.  Automatic lung segmentation for accurate quantitation of volumetric X-ray CT images , 2001, IEEE Transactions on Medical Imaging.

[44]  S. Lai,et al.  Cardiovascular function in multi-ethnic study of atherosclerosis: normal values by age, sex, and ethnicity. , 2006, AJR. American journal of roentgenology.

[45]  D. Jacobs,et al.  The association between physical activity and subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis. , 2008, American journal of epidemiology.

[46]  V. Peinado,et al.  Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD , 2002, European Respiratory Journal.

[47]  A. Liebow Pulmonary emphysema with special reference to vascular changes. , 2015, The American review of respiratory disease.

[48]  J. Marcus,et al.  The effect of right ventricular hypertrophy on left ventricular ejection fraction in pulmonary emphysema. , 1997, Chest.

[49]  D. Bluemke,et al.  Traditional cardiovascular risk factors in relation to left ventricular mass, volume, and systolic function by cardiac magnetic resonance imaging: the Multiethnic Study of Atherosclerosis. , 2006, Journal of the American College of Cardiology.

[50]  P. Paré,et al.  Measurement of lung expansion with computed tomography and comparison with quantitative histology. , 1995, Journal of applied physiology.

[51]  J. Ellis,et al.  Left ventricular ejection fraction in severe chronic obstructive airways disease. , 1975, The American journal of medicine.

[52]  G. Joos,et al.  Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema , 2006, Respiratory research.

[53]  Milan Sonka,et al.  Matching and anatomical labeling of human airway tree , 2005, IEEE Transactions on Medical Imaging.

[54]  A. Chaouat,et al.  Severe pulmonary hypertension and chronic obstructive pulmonary disease. , 2005, American journal of respiratory and critical care medicine.

[55]  D A Lynch,et al.  Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. , 2001, American journal of respiratory and critical care medicine.

[56]  G. Baum,et al.  Left ventricular function in chronic obstructive lung disease. , 1971, The New England journal of medicine.

[57]  M. I. Ferrer,et al.  Influence of chronic pulmonary disease on the heart and circulation. , 1951, The American journal of medicine.