Cardiac Dysfunction In Exacerbations of Chronic Obstructive Pulmonary Disease

Abstract

Introduction Acute cardiac complications frequently occur during exacerbations of chronic obstructive pulmonary disease (COPD) and are associated with a high mortality. They may be difficult to recognise clinically, but cardiac biomarkers, natriuretic peptides and troponins, are commonly abnormal in patients with COPD exacerbations. The mechanisms of cardiac dysfunction in COPD exacerbations are not well understood and it is unclear if cardiac biomarkers can be used to shed light on mechanisms, assess prognosis, and guide treatment. This thesis studied these cardiac biomarkers in two prospective cohort studies of patients hospitalised with COPD exacerbations. Methods The COPDEC study was a five-year follow-up of 247 patients hospitalised in 2006-2007. The BREATHE study was a one-year follow-up of 176 patients hospitalised in 2012-2013. In both studies, amino-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin T, and clinical indicators of the severity of COPD exacerbation were measured and data on mortality over the follow-up period were collected. The Prognostic Value Of Cardiac Biomarkers In Exacerbations Of COPD In an earlier report on the one-year follow-up of the COPDEC study, high NT-proBNP and troponin T were independent predictors of thirty-day mortality but not late mortality. In the five-year follow-up of the COPDEC study, high NT-proBNP and troponin T did not predict mortality after thirty days. The BREATHE study replicated the findings on early mortality but high cardiac biomarkers also predicted mortality at one year. The Time-Course Of Cardiac Biomarkers During Exacerbations Of COPD Serial measurements of cardiac biomarkers in the BREATHE study found that NT-proBNP levels were higher at twelve hours than at admission and 10% of patients had a clinically significant troponin T rise in the first twelve hours. Nebulised bronchodilators and blood salbutamol levels predicted the rise in NT-proBNP between admission and twelve hours, independently of the clinical severity of the exacerbation, and had borderline associations with clinically significant troponin T rises at twelve hours. Cardiac Biomarkers And Other Measures Of Cardiac Dysfunction In both cohorts, patients with high cardiac biomarkers were more likely to have ischaemic changes, left ventricular hypertrophy, tachycardia, atrial fibrillation/flutter on electrocardiogram, and cardiomegaly on chest radiography than patients with normal cardiac biomarkers. A subgroup of patients in the BREATHE cohort underwent cardiac magnetic resonance imaging within two weeks of admissions and at stability thirty days later. Biventricular systolic dysfunction was common but not different between those with high and normal NT-proBNP. A high NT-proBNP at admission was associated with biventricular enlargement in both acute and stable scans. Risk Score For Exacerbations Of COPD The COPDEC cohort was used to derive a composite prognostic score: the CANT score that combined high CURB-65 score, acidaemia, high NT-proBNP, and high troponin T. This was validated in the BREATHE cohort. The CANT score performed better than existing scores in predicting thirty-day mortality. Conclusions High NT-proBNP and troponin T are common in patients hospitalised with exacerbations of COPD and are associated with a poor short-term prognosis. High-dose bronchodilators may worsen cardiac dysfunction. Cardiac biomarkers combined with clinical scores improve risk stratification in COPD exacerbations