Does Patent Foramen Ovale Size Matter in Men and Women

A patent foramen ovale (PFO) is present in ~30% of the general population. The PFO has historically been considered to be trivial. However, recent work by the investigator's group and others has identified that, compared to individuals without a PFO, those with a PFO have worse pulmonary gas exchange efficiency, have a higher core body temperature, blunted ventilatory responses to chronic hypoxia and acute carbon dioxide and increased susceptibility to altitude illnesses such as acute mountain sickness, and high altitude pulmonary edema (Lovering, Elliott & Davis J Appl Physiol 2016). Specific to this application,subjects with a PFO may have worse pulmonary gas exchange efficiency because a PFO is a potential source of right-to-left shunt that will make pulmonary gas exchange efficiency worse. If true, then this may negatively impact exercise capacity and/or exercise tolerance. Further, in those with a PFO compared to those without, preliminary work from the investigator's lab indicates that there may be an effect of PFO size on pulmonary gas exchange efficiency. This is such that those with a large PFO (grade 3 or higher) display significantly worse gas exchange efficiency compared to those with a small (grade 2 or lower) or no PFO,even at low exercise workloads. Additionally, the investigators were curious as to whether there would be a sex effect, but due to logistical constraints, the investigators were unable to recruit an equal number of female and male subjects. Thus, in addition to the potential size effect on the investigators outcome measures, the investigators would like to build on this work by examining the potential effect of biological sex. Although a PFO has been traditionally considered to have a minimal impact of physiology and pathophysiology, emerging evidence suggests this may not be the case. The investigator's lab is focused on understanding how and why a relatively small hole in the heart (PFO) can have a relatively large impact on cardiopulmonary and respiratory physiology, and how these impacts may be based on the size of the PFO.

Study Overview

• Status: Recruiting
• Conditions: Patent Foramen Ovale

• Study Type: Observational
• Enrollment (Anticipated): 28

Contacts and Locations

• Study Contact: Name: Andrew Lovering, PhD; Phone Number: 541-346-0831; Email: lovering@uorgeon.edu

Study Locations

• United States
  • Oregon
    • Eugene, Oregon, United States, 97403
      • Recruiting
      • Cardiorespiratory and Pulmonary Physiology Lab
      • Contact: Andrew Lovering, PhD; Phone Number: 541-346-0831; Email: lovering@uoregon.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Healthy adults aged 18-40 with and without a PFO.

Description

Inclusion Criteria:

• Men and women aged 18-40
• Known to have/not have a PFO.

Exclusion Criteria:

• Previous history of coronary artery disease(ischemic heart disease such as angina, heart attack, myocardial infarction).
• Failure of Modified Allen's Test in both hands.
• Currently taking medications or herbal supplements for any heart or respiratory disease that they cannot stop taking for 48 hrsprior to testing (seasonal allergy medication not included in exclusion medications).
• Lidocaine, nitroglycerine or heparin allergy.
• Women who are pregnant or trying to become pregnant.
• Previous history of any condition that would prevent the subject from performing cycle ergometer exercise (for exercise study only).

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
No PFO; Research subjects who present no evidence of PFO - IE no appearance of saline contrast microbubbles within 3 cardiac cycles
Small PFO; Research subjects who present evidence of having a small PFO or ASD - IE appearance of 1-11 saline contrast microbubbles within 3 cardiac cycles
Large PFO; Research subjects who present evidence of having a large PFO - IE appearance of 12+ saline contrast microbubbles within 3 cardiac cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
alveolar-arterial difference in oxygen	difference in the partial pressure of oxygen between the alveoli (calculated) and arterial blood (direct measure)	Baseline
aerobic exercise capacity	ability to utilize oxygen while exercising, AKA Vo2MAX	Baseline
six-minute walk test	distance covered in 6 minutes of walking	Baseline
minute flow of intrapulmonary areterio-venous anastamoses (QIPAVA)	minute flow through intrapulmonary arteriovenous anastamoses	Baseline
core body temperature	subject's core body temperature as measured through an ingestible pill	Baseline
level of tumor necrosis factor alpha	inflammatory marker	Baseline
level of C-C motif cytokine 2	inflammatory marker	Baseline
level of interferon alpha 2	inflammatory marker	Baseline
level of interferon gamma	inflammatory marker	Baseline
level of interleukin 1 beta	inflammatory marker	Baseline
level of interleukin 6	inflammatory marker	Baseline
level of interleukin 8	inflammatory marker	Baseline
level of interleukin 10	inflammatory marker	Baseline
level of interleukin 12p70	inflammatory marker	Baseline
level of interleukin 17 alpha	inflammatory marker	Baseline
level of interleukin 18	inflammatory marker	Baseline
level of interleukin 23	inflammatory marker	Baseline
level of interleukin 33	inflammatory marker	Baseline
level of myoglobin	inflammatory marker	Baseline
level of myeloid-related protein 8/14	inflammatory marker	Baseline
level of neutrophil gelatinase-associated lipocalin	inflammatory marker	Baseline and 3 months post percutaneous closure
level of c-reactive protein	inflammatory marker	Baseline
matrix metallopeptidase 2	inflammatory marker	Baseline and 3 months post percutaneous closure
level of osteopontin	inflammatory marker	Baseline
level of myloperoxidase	inflammatory marker	Baseline
level of Serum amyloid A	inflammatory marker	Baseline
level of insulin like growth factor binding protein 4	inflammatory marker	Baseline
level of intracellular adhesion molecule 1	inflammatory marker	Baseline
level of vascular cell adhesion protein 1	inflammatory marker	Baseline
level of metallopeptidase 9	inflammatory marker	Baseline
level of Cystatin C	inflammatory marker	Baseline

Collaborators and Investigators

• Sponsor: University of Oregon

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: April 1, 2019
• First Submitted That Met QC Criteria: April 2, 2019
• First Posted (Actual): April 5, 2019

Study Record Updates

• Last Update Posted (Actual): October 14, 2022
• Last Update Submitted That Met QC Criteria: October 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Septal Defects, Atrial; Heart Septal Defects; Foramen Ovale, Patent
• Other Study ID Numbers: 04302018.049

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No