Effects of Dynamic Hyperinflation on Left Ventricular Diastolic Function in Healthy Subjects - A Randomized Controlled Crossover Trial

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.

Keywords: chronic obstructive pulmonary disease; diastolic dysfunction; diastolic filling; dynamic hyperinflation; heart failure; positive end-expiratory pressure.

Conflict of interest statement

MU received grants from Nycomed Pharma as well as speaker fees and fees for advisory boards from Astra-Zeneca, Böhringer Ingelheim, Dräger, Sanitas, and Grünenthal. IS received personal fees for lectures from Astra-Zeneca, AOP, Orphan, Böhringer-Ingelheim and Chiesi. AM and EG-S have no conflicts of interest to declare. OB received unrestricted research grants from public governmental federal institutions and and from pharma industry (Menarini, Böhringer-Ingelheim, Chiesi, GSK, Pfizer, TEVA, Astra-Zeneca Air Liquide, MSD) as a member of the Ludwig Boltzmann Institute for Lung Health for the Austrian LEAD Study. He received personal fees for lecture and as member of advisory boards from Roche, Takeda, Nycomed and Astra-Zeneca. G-CF reports speaker fees and fees for advisory boards from Boehringer Ingelheim, Menarini, Janssen-Cilag, Novartis, Insmed Germany, Getinge, Draeger, CSL Behring, Orion Pharma, Astra Zeneca, Fresenius, Chiesi, Glaxo-Smith Kline, Roche; G-CF reports educational grants from Janssen-Cilag. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Urban, Mayr, Schmidt, Grasmuk-Siegl, Burghuber and Funk.

Figures

Figure 1

Participant flow chart and randomization. ERB, expiratory resistance breathing; TP, tachypnea.

Figure 2

Line chart of changes in E/A (A) and E/e' (B) during tachypnea and expiratory resistance breathing with diameters of 3 mm (ERB1), 2 mm (ERB2), and 1.5 mm (ERB3). TP, tachypnea; ERB, expiratory resistance breathing; SB, spontaneous breathing.

Figure 3

Scatter plot of the association between left ventricular diastolic function and dynamic hyperinflation of the lungs. Individual observations (1–14) are color coded. E/A_HR60, ratio of transmitral E- to A-wave corrected for a heart rate of 60/min; PEEPi log, log transformed intrinsic positive end-expiratory pressure (cmH2O).