Study shows improvement in cardiac function in COPD patients with pulmonary hyperinflation

Although cardiovascular diseases are known as the most common co-morbidity in patients with COPD, the direct impact of respiratory medication on cardiac function has been under-investigated. In a collaboration of the BREATH research groups of Prof. Hohlfeld at the Fraunhofer Institute for Toxicology and Experimental Medicine, Prof. Welte in the Clinic for Pulmonology and Prof. Vogel-Claussen at the Institute for Diagnostic Radiology of the MHH, a protocol was created in which for the first time, the effect of a combination therapy with two bronchodilators on the improvement of cardiac function in COPD patients with pulmonary hyperinflation was investigated.

COPD is the world's most common chronic lung disease. Among the top ten most common deaths, it is the only one whose incidence is increasing. In Germany alone, about 7 million people have been diagnosed. The course of the disease in COPD patients is characterized primarily by a progressive deterioration in lung function and a decrease in exercise capacity. Inflammatory processes in the respiratory tract, caused by inhaled pollutants, especially by cigarette smoke, lead to an increasing destruction of the bronchial and lung structure with typical limitations of lung function. Typical for COPD is an increase in the residual volume in the lungs as a sign of pulmonary hyperinflation. This seems to affect cardiac function, leading to a reduction in ventricular filling and a decrease in cardiac output, which in turn limits exercise capacity.
Bronchodilators can alleviate this process by causing bronchial dilatation by lowering the tone of the bronchial muscles while reducing hyperinflation. The recommendations of the German Society for Pulmonology and Respiratory Medicine (DGP) currently provide for the administration of long-acting bronchodilators in COPD patients from severity grade II, initially as part of a monotherapy and later as part of the dual bronchodilation therapy.
Although an influence of pulmonary hyperinflation on cardiac function is obvious, the direct influence of dual bronchodilation therapy (beta-2 agonists, LABA and anticholinergics, LAMA, as a fixed combination) on both organ systems has not yet been studied simultaneously. As part of the Novartis-funded CLAIM study, Prof. Dr. med. Jens Hohlfeld, Head of Airway Research at the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) and Prof. Dr. med. Tobias Welte, Director of the Clinic for Pulmonology at Hannover Medical School (MHH) together with Prof. Dr. med. Jens Vogel-Claussen, Chief Senior Physician at the Institute for Diagnostic and Interventional Radiology at MHH, investigated the direct relationship between pulmonary and cardiac changes during therapy for the first time.
The researchers at BREATH, the Hannover site of the German Center for Lung Research, are the first to use left ventricular end-diastolic volume (LV-EDV), measured by magnetic resonance imaging (MRI), as the primary endpoint in a clinical trial. In total, 62 patients with moderate to severe COPD (GOLD II - III) and known pulmonary hyperinflation were treated once a day with the drug combination LABA / LAMA or placebo for a period of 14 days. Mechanistic improvements of the pulmonary and cardiac parameters were already observed after this comparatively short period of time. Noteworthy above all was the average increase in LV EDP from 55.46 ml/m2 to 61.76 ml/m2. The observed reduction in pulmonary hyperinflation was much more pronounced than in previous clinical trials. The simultaneous improvement of the heart index with unchanged resting pulse mechanistically indicates an increase in stroke volume by reducing hyperinflation. This substantial improvement in the studied functional parameters also resulted in a subjective decrease in the and improvement of patient reported outcome parameters, as measured by the COPD Assessment Test (CAT) and the Transition Dyspnea Index (TDI), two established methods for determining the extent of air distress.
All results of the CLAIM study will be published on February 21, 2018 in the internationally renowned journal Lancet Respiratory Medicine. CLAIM thus makes a valuable contribution towards a better understanding of the impact of pulmonary function changes on cardiovascular parameters in COPD patients. The results of the study provide a first indication that dual bronchodilation therapy may be clinically useful for COPD patients with early signs of hyperinflation to increase their performance. Further studies in COPD patients with impaired cardiac function are needed to determine the effects of bronchodilation on the progression of heart disease.

Source: Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial. Jens M Hohlfeld, Jens Vogel-Claussen, Heike Biller, Dominik Berliner, Korbinian Berschneider, Hanns-Christian Tillmann, Simone Hiltl, Johann Bauersachs, Tobias Welte. Lancet Respir Med 2018. Published Online February 21, 2018.


Foto: Tom Figiel

Prof. Dr. Jens Hohlfeld, Prof. Dr. Jens Vogel-Claussen und Prof. Dr. Tobias Welte, DZL-PIs at site BREATH