Chronic Obstructive Pulmonary Disease: When Pulmonologists Do Something Good for the Heart.

Lung hyperinflation provides a mechanistic link between expiratory flow limitation and dyspnea in patients with chronic obstructive pulmonary disease (COPD) (1). Exertional dyspnea in turn leads to exercise intolerance and physical inactivity, which trigger the downward spiral of the disease (2, 3). As a consequence, deflation of the lung is an important goal of pharmacological maintenance therapy in COPD (4). According to some studies, this therapeutic approach improves exertional dyspnea, exercise intolerance (1, 5, 6), and physical inactivity in daily life (6, 7). So far, so good. The pharmacotherapy currently used to deflate the lung, either by a long-acting b2-agonist or a long-acting muscarinic antagonist, might put patients at risk for adverse cardiovascular events (8, 9). These potential adverse effects are always a major concern of COPD therapy, as patients with COPD are also frequently affected by cardiac disease (10). Cardiac manifestations of COPD, in turn, are attributed to the high frequency of comorbid coronary artery disease or mild pulmonary hypertension secondary to severe COPD (10). Is this all there is to the story of pharmacotherapy and cardiac dysfunction in COPD? Did we ever think outside the box, or inside the (rib) cage? Did we ever evaluate whether lung hyperinflation negatively affects cardiac function, and whether we could potentially do something good for the heart when we deflate the lung by pharmacotherapy? A few colleagues have investigated these questions, as summarized in a recent editorial in the Journal (11) and in another review article (12). Butler and coworkers demonstrated that dynamic hyperinflation induces left ventricular dysfunction, as indicated by an increase in pulmonary capillary wedge pressure at right heart catheterization, independent of an increase in intrathoracic pressure (Figure 1) (13, 14). Subsequently, impaired left ventricular filling processes associated with a reduced preload were observed at echocardiography in patients with COPD (15, 16); lung hyperinflation could be related to those impaired filling processes (17). Furthermore, it was shown that either emphysema or hyperinflation is related to a decrease in right ventricular volume and diameter during diastole (17, 18), reduced intrathoracic blood volume (19), reduced pulmonary vein dimensions (20), decreased left ventricular volume and diameter during diastole (17, 21), and reduced stroke volume (21). Finally, developing an obstructive lung function pattern early in life is associated with an underfilling of the left heart and low cardiac output (22). Several studies performed in patients with advanced emphysema showed that lung volume reduction surgery leads to improved cardiac performance, as indicated by an improved oxygen pulse (23) and improved left ventricular filling and function (24). Furthermore, pulmonary capillary wedge pressure decreases in patients undergoing lung volume reduction surgery (25). However, few studies have evaluated the effects of pharmacological lung deflation therapy on cardiac volume and function in patients with COPD (26, 27). Travers and colleagues showed that the long-acting muscarinic antagonist tiotropium improves the oxygen pulse on exercise (26), whereas Santus and colleagues detected significant improvements in right ventricular compliance indexes at echocardiography after lung deflation with the long-acting b2-agonist indacaterol (27). To my knowledge, no other studies have looked into this topic. Thus, a well-designed study to evaluate the effects of pharmacological lung deflation therapy on cardiac function and cardiac volumes has been eagerly awaited. In this issue of the Journal, Stone and colleagues (pp. 717–726) provide the missing piece of the puzzle by presenting landmark data that clearly demonstrate an effect of pharmacological lung deflation therapy on cardiac structure and function (28). In my opinion, the changes in right and left ventricular end-diastolic volumes and right and left ventricular stroke volumes are the most impressive data, as they provide further evidence of an “treatable underfilling” of the heart in hyperinflated patients with COPD. However, like any good piece of work, this study leaves us with further questions. First, could cardiac function improve even more if two bronchodilators (a long-acting b2-agonist and longacting muscarinic antagonist) are used? Second, considering the necessity of lifelong treatment in patients with COPD, how long can these effects be demonstrated ? Third, what is the clinical relevance of these changes? But now that this first mechanistic study is available, I am sure that further studies on this topic will help us find answers to these and other questions that may arise. n