Abstract
Objective: Diastolic dysfunction of the left ventricle is common in patients with chronic obstructive pulmonary disease (COPD). Dynamic hyperinflation has been suggested as a key determinant of reduced diastolic function in COPD. We aimed to investigate the effects of induced dynamic hyperinflation on left ventricular diastolic function in healthy subjects to exclude other confounding mechanisms associated with COPD.Design: In this randomized controlled crossover trial (NCT03500822, https://www.clinicaltrials.gov/), we induced dynamic hyperinflation using the validated method of expiratory resistance breathing (ERB), which combines tachypnea with expiratory resistance, and compared the results to those of tachypnea alone. Healthy male subjects (n = 14) were randomly assigned to the ERB or control group with subsequent crossover. Mild, moderate, and severe hyperinflation (i.e., ERB1, ERB2, ERB3) were confirmed by intrinsic positive end-expiratory pressure (PEEPi) using an esophageal balloon catheter. The effects on diastolic function of the left ventricle were measured by transthoracic echocardiographic assessment of the heart rate-adjusted transmitral E/A-ratio and E/e'-ratio.Results: We randomly assigned seven participants to the ERB group and seven to the control group (age 26 [24-26] vs. 24 [24-34], p = 0.81). Severe hyperinflation decreased the E/A-ratio compared to the control condition (1.63 [1.49–1.77] vs. 1.85 [0.95–2.75], p = 0.039), and moderate and severe ERB significantly increased the septal E/e'-ratio. No changes in diastolic function were found during mild hyperinflation. PEEPi levels during ERB were inversely correlated with the E/A ratio (regression coefficient = −0.007, p = 0.001).Conclusions: Our data indicate dynamic hyperinflation as a determinant of left ventricular diastolic dysfunction in healthy subjects. Therapeutic reduction of hyperinflation might be a treatable trait to improve diastolic function in patients with COPD.
Highlights
Chronic obstructive pulmonary disease (COPD) is among the most common causes of death worldwide [1]
The amount of hyperinflation, as measured by positive end-expiratory pressure (PEEPi), was inversely associated with the E/A ratio. These findings indicate that diastolic dysfunction is determined by intrathoracic pressures and strengthen the role of hyperinflation as a therapeutic target for improving left ventricular diastolic filling and function in COPD
The amount of dynamic hyperinflation during expiratory resistance breathing (ERB) is comparable to the values observed in patients with COPD [20]
Summary
Chronic obstructive pulmonary disease (COPD) is among the most common causes of death worldwide [1]. Despite decreasing mortality rates in some Western countries, the global mortality attributable to COPD has continued to rise over the last decades [2]. Cardiovascular comorbidities are among the most relevant drivers of mortality in patients with COPD [3, 4]. Diastolic dysfunction of the left ventricle, along with systolic heart failure, coronary artery disease, and hypertension, has emerged as one of the most frequent comorbidities in COPD [5,6,7]. The prevalence of diastolic dysfunction is variable and can reach as high as 90%, independent of disease severity, in COPD [8, 9]. Patients with diastolic dysfunction are much more likely to have airflow limitation than patients with systolic dysfunction [10]
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