Impact of Hypoxia on Resting and Exertional Right Ventricular Performance

Hypoxia Clinical Trial

Official title:

Impact of Hypoxia on Resting and Exertional Right Ventricular Performance - A PILOT STUDY

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05272514
• Other study ID #: 21-4354
• Status: Completed
• Start date: April 15, 2022
• Est. completion date: December 15, 2022

Study information

• Verified date: May 2023
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to better understand how hypoxia (low oxygen) affects resting and exertional right ventricular function in healthy individuals.

Description:

The right ventricle plays a critical role in exercise. As workload increases with exercise, the right ventricle augments contractility and lusitropy (diastolic relaxation) to accommodate increased venous return (preload) and pulmonary arterial pressure (afterload). Using gold-standard pressure-volume analysis, the investigators have shown that impairments in right ventricular function limit functional capacity among individuals with cardiovascular disease, heart failure and pulmonary hypertension. In addition, the investigators have characterized right ventricular function during exercise in the healthy heart using these techniques. Hypoxia increases pulmonary arterial pressure via hypoxic pulmonary vasoconstriction. By increasing right ventricular afterload, hypoxia may compromise exercise capacity. However, data regarding the impact of hypoxia on right ventricular performance are lacking.

This is a human physiology study of resting and exertional right ventricular function under control (normoxic) and hypoxic conditions. The investigators will use pressure-volume analysis in conjunction with Swan-Ganz catheterization and echocardiography to assess right ventricular performance in healthy individuals at rest and during exercise in normoxia and hypoxia. The study protocol consists of three visits.

• Visit 1: Non-invasive symptom-limited cardiopulmonary exercise test under normoxic conditions (FiO2= 0.21).

• Visit 2: Non-invasive symptom-limited cardiopulmonary exercise test under hypoxic conditions (FiO2=0.12).

• Visit 3: Invasive resting and exertional hemodynamic assessment under normoxic and hypoxic conditions

In Visits 1 and 2, heart rate/rhythm, oxygen saturation, blood pressure, gas exchange parameters (oxygen uptake [VO2], carbon dioxide production [VCO2], and minute ventilation), and rated perceived exertion will be monitored. Cardiopulmonary exercise testing (CPET) will be performed on an upright cycle ergometer with workload starting at 0 Watts and increasing every 2 minutes until volitional exhaustion with maximum workload at 8-12 minutes. The order of Visits 1 and 2 will be randomized to reduce the potential for bias from a learning/ordering effect.

In Visit 3, the same non-invasive measurements will be obtained. Additionally, right heart catheterization with Swan-Ganz catheter and conductance catheter placement will be performed. This will provide gold-standard hemodynamic and pressure-volume loop analysis to measure outcomes of right ventricular contractility, lusitropy (diastolic relaxation), afterload, and ventricular-arterial coupling. First, participants will complete submaximal exercise at FiO2=0.21. Submaximal exercise will include 5 minutes at 50% of baseline maximal oxygen uptake (VO2max achieved during Visit 1). After 20 minutes' rest, hemodynamic measurements will be obtained at rest at FiO2 0.21, 0.17, 0.15 and 0.12 to characterize the impact of progressive hypoxia on resting right ventricular hemodynamics. Participants will then perform submaximal exercise (50% VO2 max from hypoxic baseline at Visit 2) at FiO2 0.12. Thereafter, participants will complete a symptom-limited CPET at FiO2 0.12 with monitoring of invasive hemodynamics.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 15, 2022
• Est. primary completion date: August 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Age 18 - 60

• For women, premenopausal status

Exclusion Criteria:

• Active cardiovascular or pulmonary disease (e.g. hypertension, coronary artery disease, cardiomyopathy, arrhythmia, valvular abnormalities, diabetes, peripheral vascular disease, tobacco use, chronic obstructive pulmonary disease, asthma, interstitial lung disease, restrictive lung disease, or pulmonary hypertension)

• Use of cardiac- or pulmonary-related medications

• Prior history of high altitude pulmonary edema or high altitude cerebral edema

• Body mass index < 18.5 or > 30

• Anemia

• Iron deficiency

• Iron supplementation (oral or intravenous) in the preceding 60 days

• Systemic anticoagulation or aspirin use that cannot be temporarily held for the study

• Pregnancy

• Non-cardiopulmonary disorders that adversely influence exercise ability (e.g. arthritis or peripheral vascular disease)

• Dedicated athletic training (defined here as spending >9 hours per week in vigorous physical activity [=6 mets])

• Regular high-altitude exercise (defined here as engaging in vigorous physical activity [=1 hour at =6 mets] at =8,000 ft for >2 days per week over the preceding 4 weeks)

• Residence at =8,000 ft for 3 or more consecutive nights in the preceding 30 days

Related Conditions & MeSH terms

• Hypoxia
• Ventricular Dysfunction
• Ventricular Dysfunction, Right

Intervention

Other:
• Hypoxia
Individuals will be exposed to varying levels of hypoxia according to the protocol detailed above.

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

References & Publications (4)

Cornwell WK 3rd, Baggish AL, Bhatta YKD, Brosnan MJ, Dehnert C, Guseh JS, Hammer D, Levine BD, Parati G, Wolfel EE; American Heart Association Exercise, Cardiac Rehabilitation, and Secondary Prevention Committee of the Council on Clinical Cardiology; and Council on Arteriosclerosis, Thrombosis and Vascular Biology. Clinical Implications for Exercise at Altitude Among Individuals With Cardiovascular Disease: A Scientific Statement From the American Heart Association. J Am Heart Assoc. 2021 Oct 5;10(19):e023225. doi: 10.1161/JAHA.121.023225. Epub 2021 Sep 9. — View Citation

Cornwell WK, Tran T, Cerbin L, Coe G, Muralidhar A, Hunter K, Altman N, Ambardekar AV, Tompkins C, Zipse M, Schulte M, O'Gean K, Ostertag M, Hoffman J, Pal JD, Lawley JS, Levine BD, Wolfel E, Kohrt WM, Buttrick P. New insights into resting and exertional right ventricular performance in the healthy heart through real-time pressure-volume analysis. J Physiol. 2020 Jul;598(13):2575-2587. doi: 10.1113/JP279759. Epub 2020 May 18. — View Citation

Smith TG, Balanos GM, Croft QP, Talbot NP, Dorrington KL, Ratcliffe PJ, Robbins PA. The increase in pulmonary arterial pressure caused by hypoxia depends on iron status. J Physiol. 2008 Dec 15;586(24):5999-6005. doi: 10.1113/jphysiol.2008.160960. Epub 2008 Oct 27. — View Citation

Smith TG, Talbot NP, Privat C, Rivera-Ch M, Nickol AH, Ratcliffe PJ, Dorrington KL, Leon-Velarde F, Robbins PA. Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials. JAMA. 2009 Oct 7;302(13):1444-50. doi: 10.1001/jama.2009.1404. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Right ventricular contractility measured by conductance catheter	End-systolic elastance (Ees) in mmHg/mL	Up to 1 hour
Primary	Right ventricular lusitropy (diastolic function) measured by conductance catheter	Minimum dp/dt in mmHg/sec	Up to 1 hour
Secondary	Right ventricular stroke work measured by conductance catheter	Area of pressure-volume loop	Up to 1 hour
Secondary	Mean pulmonary artery pressure measured by right heart catheterization	In mmHg	Up to 1 hour
Secondary	Cardiac output derived from right heart catheterization	In L/min, calculated by Fick equation	Up to 1 hour
Secondary	Workload	Workloads attained with submaximal and maximal exercise testing	Up to 1 hour
Secondary	Maximal oxygen uptake	VO2max achieved in maximal exercise testing	Up to 1 hour
Secondary	Plasma acylcarnitine 10:0 measured by peripheral venous metabolomics (ultra-high performance liquid chromatography coupled to mass spectrometry)	Relative ion count	Up to 1 hour
Secondary	Red blood cell acylcarnitine 10:0 measured by peripheral venous metabolomics (ultra-high performance liquid chromatography coupled to mass spectrometry)	Relative ion count	Up to 1 hour