PIMR and Pulmonary Vascular Disease

NCT05843461 | Completed

• 1 other identifier: IRB#22-001643
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The findings from this innovative, first-in-man, prospective pilot study will elucidate the role of PIMR and RV-IMR in pre-capillary PH. The study cohort will consist of patients with pulmonary pressures ranging from normal (advanced lung disease patients undergoing lung transplant evaluation) to severe PH (PAH and CTEPH patients), and thus will allow for identification of a PIMR cutoff. Participants will include: 1) advanced lung disease patients undergoing bilateral heart catheterization as part of their pre-lung transplant work-up, and 2) newly referred patients to PAH and CTEPH clinics undergoing bilateral heart catheterization as part of standard of care work-up. All participants will undergo PIMR testing, and those with pre-capillary PH will also undergo pulmonary OCT and measurement of RV-IMR. The study seeks to define the relationship between PIMR and PH and to establish the PIMR threshold that identifies pulmonary microvascular dysfunction as well as to evaluate the association of PIMR and pulmonary vascular remodeling on OCT in patients with pre-capillary PH. In addition, the study will assess the relationship between RV-IMR and RV pressure overload among patients with pre-capillary PH.

Conditions

Pulmonary Hypertension

Keywords

Pulmonary Hypertension; Pulmonary Arterial Hypertension; Index of Microcirculatory Resistance; Chronic Thromboembolic Disease; Pulmonary Index of Microcirculatory Resistance

Outcome Measures

Primary Outcomes (5)

• Pulmonary Index of Microcirculatory Resistance (PIMR)

  PressureWire advanced to distal third of segmental pulmonary artery (PA) for measurement of pulmonary hemodynamics. The derivation of IMR involves the application of Ohm's law (V=IR) to the coronary microcirculatory circuit, where the relationship between resistance (R) = IMR, voltage (V) = pressure (P), and current (I) = flow (Q) can be expressed as follows: IMR = ∆P/Q. ∆P = the change in pressure across the microvasculature (mean distal coronary artery pressure \[Pd\] - coronary venous pressure (Pv); Pv is typically disregarded because it is negligible relative to Pd. Based on the principles of thermodilution, flow is inversely proportion to mean transit time (Q \~ 1/Tmn). Lastly, the minimal achievable resistance occurs during maximal hyperemic flow when all available microvessels have theoretically been recruited. Hence, the calculation of IMR simplifies to the following formula: IMR = Pd (pulmonary artery) x TmnHyp.

  Baseline

• Right Ventricle Index of Microcirculatory Resistance (RV-IMR)

  PressureWire advanced to distal third of acute marginal branch of the right coronary artery (RCA) for measurement of pulmonary hemodynamics. The derivation of IMR involves the application of Ohm's law (V=IR) to the coronary microcirculatory circuit, where the relationship between resistance (R) = IMR, voltage (V) = pressure (P), and current (I) = flow (Q) can be expressed as follows: IMR = ∆P/Q. ∆P = the change in pressure across the microvasculature (mean distal coronary artery pressure \[Pd\] - coronary venous pressure (Pv); Pv is typically disregarded because it is negligible relative to Pd. Based on the principles of thermodilution, flow is inversely proportion to mean transit time (Q \~ 1/Tmn). Lastly, the minimal achievable resistance occurs during maximal hyperemic flow when all available microvessels have theoretically been recruited. Hence, the calculation of IMR simplifies to the following formula: IMR = Pd (RCA marginal branch) x TmnHyp.

  Baseline

• OCT-derived pulmonary artery wall thickness

  A Dragonfly Optis OCT catheter (Abbott) will be advanced over the PressureWireX to the distal left lower lobe segmental pulmonary artery (luminal diameter \< 5 mm and minimal length of 50 mm). OCT images of the pulmonary artery will be recorded via automatic pullback and analyzed offline in a blinded manner.

  Baseline

• OCT-derived thickness-diameter ratio

  A Dragonfly Optis OCT catheter (Abbott) will be advanced over the PressureWireX to the distal left lower lobe segmental pulmonary artery (luminal diameter \< 5 mm and minimal length of 50 mm). OCT images of the pulmonary artery will be recorded via automatic pullback and analyzed offline in a blinded manner.

  Baseline

• OCT-derived wall-area ratio

  Baseline

Study Arms (3)

Controls

10 patients without pulmonary hypertension (mean PA pressure less than 20 mmHg on RHC)

Other: Pulmonary Index of Microcirculatory Resistance

PAH

10 patients with PAH

Other: Pulmonary Index of Microcirculatory Resistance; Other: Right Ventricle Index of Microcirculatory Resistance; Other: Pulmonary artery OCT

CTEPH

10 patients with CTEPH

Other: Pulmonary Index of Microcirculatory Resistance; Other: Right Ventricle Index of Microcirculatory Resistance; Other: Pulmonary artery OCT

Interventions

Pulmonary Index of Microcirculatory Resistance OTHER

PIMR measurement involves placing a coronary pressure wire in the pulmonary arteries and making pressure/time measurements during maximal flow down the artery. PIMR of the right and left pulmonary arteries will be obtained.

Also known as: PIMR

CTEPH; Controls; PAH

Right Ventricle Index of Microcirculatory Resistance OTHER

RV-IMR measurement involves placing a coronary pressure wire in the acute marginal branch of the right coronary artery and making pressure/time measurements during maximal flow down the artery.

Also known as: RV-IMR

CTEPH; PAH

Pulmonary artery OCT OTHER

OCT of the pulmonary artery involves advancing an OCT catheter over the pressure wire to image the pulmonary artery. OCT of the right and left pulmonary arteries will be performed.

CTEPH; PAH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients scheduled to undergo standard-of-care right and left heart catheterization either for evaluation of suspected or known pulmonary hypertension (PAH or CTEPH) or for lung transplant evaluation in the setting of advanced lung disease

You may qualify if:

• ≥18 years old
• Able to provide informed written consent.
• Patients with 1) advanced lung disease requiring standard-of-care bilateral heart catheterization as part of lung transplant evaluation in whom mPAP \< 20 mmHg on RHC, or 2) PAH/CTEPH (i.e. pre-capillary PH) undergoing standard-of-care bilateral heart catheterization as part of their work-up/treatment

You may not qualify if:

• Contraindicated to undergo fluoroscopy and/or coronary angiography (e.g. pregnancy)
• Chronic kidney disease (serum creatinine ≥ 2.0 mg/dL)

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Abbott: collaborator

Study Sites (1)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Rushi Parikh, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 24, 2023
• First Posted: May 6, 2023
• Study Start: January 10, 2023
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: December 5, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)