Effects of Dynamic Hyperinflation on the Left-ventricular Diastolic Function in Healthy Male Subjects

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

Effects of Dynamic Hyperinflation on the Left-ventricular Diastolic Function in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03500822
• Other study ID #: Hyperstolic-COPD
• Status: Completed
• Phase: N/A
• First received: February 9, 2018
• Last updated: April 15, 2018
• Start date: November 2016
• Est. completion date: September 29, 2017

Study information

• Verified date: April 2018
• Source: Otto Wagner Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to identify whether actively induced dynamic hyperinflation can cause left-ventricular diastolic dysfunction in healthy male subjects in order to explore the mechanisms of developing cardiac dysfunctions in patients with COPD.

Description:

Cardiovascular diseases, especially left-ventricular diastolic dysfunction, are among the most frequent reasons for morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD).

Dynamic hyperinflation is one of the expected pathophysiological mechanisms in the multifactorial genesis of this left-ventricular diastolic dysfunction in patients with COPD.

The novel concept of Expiratory Stenosis Breathing (ESB) is based on the method of Metronome-Paced Tachypnea (MPT) of Cooper et al. Therefore the investigators use a metronome to indicate a specific breathing frequency (BF) and the relation of inspiration : expiration (I : E) in order to let subjects hyperinflate.

Subjects get split into two groups each hyperinflating three times for 90sec by one of the two methods before doing a cross-over and switch groups to do the same in the other group. At the end of the 90sec there is a measurement of the Inspiratory Capacity (IC) and an echocardiography in order to objectify dynamic hyperinflation respectively the change in diastolic function.

During ESB participants hyperinflate with a BF - 30/min and a I : E - 1 : 3. In addition they have to breathe through an expiratory-effective stenosis (3, 2 and 1,5mm) on the mouthpiece of the pneumotachograph to simulate the collapsing airways in COPD-patients. In contrast, during MPT subjects hyperinflate with a BF - 40/min, I : E - 1 : 1; BF - 40/min, I : E - 1 : 2; BF - 30/min, I : E - 1 : 2.

During the whole trial investigators measure Intrinsic Positive Endexpiratory Pressure (PEEPi) in order to objectify the dynamic hyperinflation more significantly.

The primary goal of this study is to assess if actively induced dynamic hyperinflation can affect diastolic function of the left ventricle.

Furthermore a correlation between the extent of dynamic hyperinflation and diastolic dysfunction should be quantified.

In addition measurement of PEEPi should validate the method of Metronome-paced Tachypnea (MPT) because the investigators hypothesize that this method does not simulate the pathophysiological circumstances in patients with COPD sufficiently.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: September 29, 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• BMI <27 kg/m2

• Lifelong nonsmoker (currently non-smoking and up to now less than 100 cigarettes)

Exclusion Criteria:

• Obstructive pulmonary diseases (asthma, COPD)

• Cardiovascular diseases (cardiac insufficiency, coronary heart diseases, hypertonia)

• Other relevant pulmonary or cardiac diseases

• Baseline E/A-ratio <1

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Procedure:
• Metronome-paced tachypnea
three cycles: breathing frequency (BF) - 40/min, inspiration : expiration (I : E) - 1 : 1; BF - 40/min, I : E - 1 : 2; BF - 30/min, I : E - 1 : 2
• Expiratory-stenosis breathing
three cycles: BF - /min, I : E - 1 : 3; stenosis: 3mm; 2mm; 1,5mm

Locations

Country	Name	City	State
Austria	Otto Wagner Spital, Dep. of Respiratory and Critical Care Medicine	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Otto Wagner Hospital

Country where clinical trial is conducted

Austria, 

References & Publications (8)

Akoumianaki E, Maggiore SM, Valenza F, Bellani G, Jubran A, Loring SH, Pelosi P, Talmor D, Grasso S, Chiumello D, Guérin C, Patroniti N, Ranieri VM, Gattinoni L, Nava S, Terragni PP, Pesenti A, Tobin M, Mancebo J, Brochard L; PLUG Working Group (Acute Respiratory Failure Section of the European Society of Intensive Care Medicine). The application of esophageal pressure measurement in patients with respiratory failure. Am J Respir Crit Care Med. 2014 Mar 1;189(5):520-31. doi: 10.1164/rccm.201312-2193CI. Review. — View Citation

Anthonisen NR, Connett JE, Enright PL, Manfreda J; Lung Health Study Research Group. Hospitalizations and mortality in the Lung Health Study. Am J Respir Crit Care Med. 2002 Aug 1;166(3):333-9. — View Citation

Barr RG, Bluemke DA, Ahmed FS, Carr JJ, Enright PL, Hoffman EA, Jiang R, Kawut SM, Kronmal RA, Lima JA, Shahar E, Smith LJ, Watson KE. Percent emphysema, airflow obstruction, and impaired left ventricular filling. N Engl J Med. 2010 Jan 21;362(3):217-27. doi: 10.1056/NEJMoa0808836. — View Citation

Cooper CB, Calligaro GL, Quinn MM, Eshaghian P, Coskun F, Abrazado M, Bateman ED, Raine RI. Determinants of dynamic hyperinflation during metronome-paced tachypnea in COPD and normal subjects. Respir Physiol Neurobiol. 2014 Jan 1;190:76-80. doi: 10.1016/j.resp.2013.08.002. Epub 2013 Aug 27. — View Citation

Evangelista A, Flachskampf F, Lancellotti P, Badano L, Aguilar R, Monaghan M, Zamorano J, Nihoyannopoulos P; European Association of Echocardiography. European Association of Echocardiography recommendations for standardization of performance, digital storage and reporting of echocardiographic studies. Eur J Echocardiogr. 2008 Jul;9(4):438-48. doi: 10.1093/ejechocard/jen174. — View Citation

López-Sánchez M, Muñoz-Esquerre M, Huertas D, Gonzalez-Costello J, Ribas J, Manresa F, Dorca J, Santos S. High Prevalence of Left Ventricle Diastolic Dysfunction in Severe COPD Associated with A Low Exercise Capacity: A Cross-Sectional Study. PLoS One. 2013 Jun 27;8(6):e68034. doi: 10.1371/journal.pone.0068034. Print 2013. Erratum in: PLoS One. 2014;9(1). doi:10.1371/annotation/b4120833-e4c6-42b5-92e9-24c396f9444e. — View Citation

Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. — View Citation

Weigt SS, Abrazado M, Kleerup EC, Tashkin DP, Cooper CB. Time course and degree of hyperinflation with metronome-paced tachypnea in COPD patients. COPD. 2008 Oct;5(5):298-304. doi: 10.1080/15412550802363428. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	E/A-ratio (absolute change between tidal breathing and smallest stenosis)	E/A-ratio will be measured by transthoracic echocardiography (Vivid S9, general electric healthcare, Fairfield, USA) according to the valid standards of The European Association of Echocardiography. This parameter represents the left-ventricular diastolic function.	At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
Secondary	E/E'-ratio	E/E'-ratio will be measured by transthoracic echocardiography (Vivid S9, general electric healthcare, Fairfield, USA) according to the valid standards of The European Association of Echocardiography. This parameter represents the left-ventricular diastolic function.	At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
Secondary	deceleration time of the E-wave transmitral (msec)	deceleration time will be measured by transthoracic echocardiography (Vivid S9, general electric healthcare, Fairfield, USA) according to the valid standards of The European Association of Echocardiography. This parameter represents the left-ventricular diastolic function.	At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
Secondary	Maximal diastolic transtricuspid flow (m/sec)	Maximal diastolic transtricuspid flow will be measured by transthoracic echocardiography (Vivid S9, general electric healthcare, Fairfield, USA) according to the valid standards of The European Association of Echocardiography. This parameter represents the left-ventricular diastolic function.	At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
Secondary	Maximal late-systolic velocity of the lateral tricuspid valve in Tissue Doppler Imaging (cm/sec)	Maximal late-systolic velocity will be measured by transthoracic echocardiography (Vivid S9, general electric healthcare, Fairfield, USA) according to the valid standards of The European Association of Echocardiography. This parameter represents the left-ventricular diastolic function.	At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
Secondary	Inspiratory Capacity	Inspiratory Capacity will be measured with a pneumotachograph (VenThor D-22/5B, ThorMedical, Budapest, Hungary). It represents the extent of dynamic hyperinflation.	At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
Secondary	Dynamic Intrinsic Positive Endexpiratory Pressure:	To objectify the dynamic hyperinflation in addition to the Inspiratory Capacity, the Intrinsic Positive Endexpiratory Pressure will be measured by the invasive application of an esophageal balloon catheter (ICU-Lab, Kleistek Engineering, Bari, Italy).	During each entire cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).