Does Patent Foramen Ovale Closure Improve Exercise Capacity & Prevent Blood Flow Through Intrapulmonary Shunt (PFO CLOSE)

The overarching goal of this study is to examine cardiopulmonary and respiratory physiology pre and post PFO/ASD closure in patients who are undergoing surgical closure of their PFO/ASD.

Study Overview

• Status: Enrolling by invitation
• Conditions: Patent Foramen Ovale
• Intervention / Treatment: Other: PFO Closure

Detailed Description

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 a higher core body temperature, significantly worse pulmonary gas exchange efficiency, 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. Specific to this application, subjects with a PFO maybe 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.

The investigator's lab group has demonstrated that hypoxemia increases blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) in healthy and subjects with COPD. When these subjects breathe 100% O2 it prevents or reduces blood flow through IPAVA. This suggests that hypoxemia per se induces blood flow through IPAVA. The blood flow through IPAVA and presence of a PFO is also associated with increased risk of stroke and/or transient ischemic attack (TIA). In addition, an atrial septal defect (ASD) is a hole within the interatrial septum, and is considered a congenital heart defect. An ASD is typically larger than a PFO, and thus, the symptoms may be worse in those with an ASD, compared to those with a PFO. Thus, some hypoxemic patients who have had a stroke or transient ischemic attack, who also have a PFO/ASD may undergo surgical closure of their PFO/ASD to prevent subsequent neurological sequelae. This surgical closure may also prevent the hypoxemia thereby reducing or preventing blood flow through IPAVA. Of note, blood flow through IPAVA has been demonstrated to be strongly correlated with TIA and/or stroke and has not previously been taken into consideration in randomized clinical trials mentioned below.

Three randomized clinical trials have determined that PFO closure is not superior to regular medical management, for the prevention of subsequent stroke and/or TIA. Nevertheless, the American Heart Association still recommends that "in patients with cryptogenic [unexplained] TIA or stroke, a PFO, and deep vein thrombosis (DVT), guidelines from the American College of Chest Physicians currently recommend vitamin K antagonist therapy for 3 months and consideration of PFO closure rather than no vitamin K antagonist therapy or aspirin therapy." Additionally, in the largest single center retrospective study performed to date, PFO closure for the purpose of preventing hypoxemia was found to result in "improvement in echocardiographic evidence of right to left shunt, New York Heart Association functional class, and oxygen requirement." Thus, PFO/ASD closure remains a potentially beneficial option for both hypoxemic and stroke/TIA patients.

Lastly, preliminary data also suggest greater levels of plasma inflammatory mediators in subjects with a PFO and systemic inflammation is associated with increased risk of cardiovascular diseases. Importantly, exercise is known to reduce so of these systemic inflammatory mediator levels. Thus, PFO/ASD closure may allow for greater exercise capacity and a subsequent reduction in inflammation.

Thus, 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/ASD) can have a relatively large impact on cardiopulmonary and respiratory physiology.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Eugene, Oregon, United States, 97403
      • Cardiorespiratory and Pulmonary Physiology Lab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women aged 18-80
• Undergoing PFO/ASD closure.
• Subject's physician will determine inclusion in either exercise or non-exercise group, based on available medical information.

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 48hrs prior 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).
• Physician determination.
• PFO/ASD deemed by referring physician as not fully closed/endothelialized at 6 months post-PFO/ASD closure procedure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pre-PFO closure; Subjects evaluated at 'baseline' prior to percutaneous closure of PFO, and re-evaluated at 3 months post percutaneous closure of PFO	Other: PFO Closure; Subject will undergo percutaneous closure of PFO/ASD utilizing FDA-approved PFO/ASD closure device(s).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in quantified pulmonary gas exchange efficiency	Quantify pulmonary gas exchange efficiency (alveolar to arterial O2 difference) and arterial oxygenation at rest and during exercise.	Baseline and 3 months post percutaneous closure
change in maximal aerobic exercise capacity (Vo2max)	Quantify aerobic exercise capacity as measured by oxygen consumption	Baseline and 3 months post percutaneous closure
change in maximal aerobic exercise capacity	Distance walked in 6 minutes (6 minute walk test)	Baseline and 3 months post percutaneous closure
Change in minute flow of intrapulmonary arterio-venuous anastamoses (QIPAVA)	Quantify QIPAVA at rest and assess recurrence of stroke or TIA at 3 months.	Baseline and 3 months post percutaneous closure
Change in plasma inflammatory markers	Quantify plasma inflammatory markers (TNFa, IL-1, 6 & CRP)	Baseline and 3 months post percutaneous closure
Change in hypercapnic ventilatory response	Measure hypercapnic ventilatory response	Baseline and 3 months post percutaneous closure
change in core body temperature measured via ingestible thermometer pill	Quantify core body temperature	Baseline and 3 months post percutaneous closure

Collaborators and Investigators

• Sponsor: University of Oregon
• Investigators: Principal Investigator: Andrew Lovering, PhD, University of Oregon

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2018
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

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 (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

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: 12132016.027

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