Acute Effect of Pulmonary Desufflation on Cardiac Performance in COPD Patients
Condition: COPD; Hyperinflation; Right Cardiac Failure
MeSH terms: Heart Failure
Study type: Interventional
Phase: Phase 4

Summary: 
      Chronic Obstructive Pulmonary disease (COPD) is one of the major clinical entities that
      causes thousands of deaths every year all over the world and weights a lot on the health care
      system of every country in terms of direct and indirect costs. The physiopathological
      modifications that characterise COPD are represented by irreversible (sometimes partially
      reversible) airflow obstruction, and bronchiolar inflammation. Lungs that develop emphysema
      lack of elastic recoil and imply increased resistances and airflow obstruction due to loss of
      lung parenchyma and supporting elastic structures. All these modifications produce air
      trapping and so lung hyperinflation. The latter is precisely the cause of the symptoms and
      particularly dyspnoea which is often heavily perceived by COPD patients and that drives to
      the limitation of daily activities. Lung hyperinflation and the other alterations that occur
      in COPD imply gas retention and increase in pulmonary vascular resistances. Considering that
      the rib cage has limited elastic properties, the effects of gas trapping and lung parenchymal
      damage on mediastinum and particularly on heart mechanics is indisputable. Together with
      alveolar hypoxia, lung hyperinflation is responsible for the development, as the disease
      progresses, of the cor pulmonale. Tha latter causes pulmonary hypertension and increased
      mechanic load during right heart chambers contraction and relaxation. Those alterations may
      effect left heart chambers too.

      Airflow obstruction in COPD is usually treated by inhaled bronchodilators and
      corticosteroids. The main and most used bronchodilators are represented by beta 2 agonists
      (short, long and ultra-long acting) and anticholinergic inhalatory drugs, which can be also
      short, long and ultra long acting. Among ultra long acting beta 2 agonists, indacaterol is
      characterised by quick onset of action (5 minutes), and guarantees an effective
      bronchodilation duration of 24 hours. It is also known that it has an important effect on
      reducing lung hyperinflation decreasing residual volume and consequently allowing an increase
      of inspiratory capacity. The purpose of our study is to evaluate the effects of indacaterol
      on lung hyperinflation in COPD subjects of any stage and with lung air trapping, and the
      consequent potential effects on heart performance evaluated by cardiac trans thoracic echo
      color doppler.
    

Detailed description: 
      In a paper recently published, Barr et al, supposed that pulmonary emphysema and bronchial
      obstruction were inversely related with ventricular telediastolic volume, with the ejection
      volume and the ejection fraction in patients with severe pulmonary disease. The mechanisms
      that are involved in the development of cor pulmonale are the increase of pulmonary vascular
      resistances, lung hyperinflation and hypoxic vascular constriction. All the mentioned
      contribute to the generation of right cardiac failure and consequently, left cardiac failure.
      The authors assessed lung hyperinflation by CT scan, pulmonary function by spirometry, and
      cardiac kinetic and mechanics by magnetic resonance. They concluded that the amount of
      emphysema and bronchial obstruction were related with a worse telediastolic left ventricular
      volume and stroke volume, no relation was found with ejection fraction. It was evident that
      patients with severe pulmonary disease and with no present cardiac diseases, had sub-clinic
      modifications that one day may lead them to the development of cor pulmonale.

      The effect of bronchodilation, with its effect on lung hyperinflation, may have a role in
      producing some modifications in this context. That's why that the aim of our study is
      centered on the evaluation of the effect of bronchodilation firstly on diastolic right
      ventricular function and also on interventricular septum motility, on the ejection fraction
      and on the kinetics of right cardiac chambers assessed by cardiac echocardiography
    

Intervention name(s): Indacaterol Fumarate; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 150 mcg inhalation powder, hard capsules, once daily; Fructose, dry inhalation powder, hard capsules via breezhaler
Other intervention name(s): Onbrez Breezhaler (Novartis International AG, Basel Switzerland); Placebo, fructose 150 mcg via Breezhaler, inhalation powder
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: COPD; Pulmonary Hyperinflation; Ultra Long Acting Beta 2 Agonists; Cor Pulmonale; Cardiac performance