Novel Index (PIMR) in PAH

Recruiting

• Conditions: Pulmonary Hypertension

• Registration Number: NCT05812976
• Lead Sponsor: University of California, Los Angeles

Brief Summary

The chief regulator of resistance in pulmonary arterial hypertension (PAH) is the small arteries. In the heart, the invasive measurement of the resistance of the small arteries has been shownto be safe, easy, reliable, and prognostic. This study is intended to translate prior work in heart arteries to the PAH space and invasively measure the resistance of the small arteries of the lung (pulmonary index of microcirculatory resistance \[PIMR\]) and the coronary artery supplying the right ventricle (acute marginal of the RCA; RV-IMR). Importantly, these measurements will be made during standard of care cardiac catheterizations (right heart catheterization \[RHC\] +/- left heart catheterization). The correlation between these new indices and the standard ones measured during RHC typically used to determine the severity of pulmonary hypertension will be analyzed. In addition, among newly diagnosed patients, the study will evaluate how these indices change 6 months after starting treatment. Finally, the association of these indices with clinical outcomes at 1 year will be assessed. The findings from this study may deliver an immediate impact to patient care by identifying a new metric to help better identify those who may benefit from a more intensive, personalized treatment regimen.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-02-01
• Study First Submitted: 2023-04-01
• Study First Submitted QC: 2023-04-01
• Study First Posted: 2023-04-14
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-02
• Last Update Posted: 2024-08-05
• Primary Completion: 2025-11-30
• Study Completion: 2025-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Diagnosis of Group 1 PAH with invasive pulmonary hypertension defined as: Mean pulmonary arterial pressure ≥ 20 mmHg, pulmonary capillary wedge pressure < 15 mmHg, and pulmonary vascular resistance ≥ 3 Wood units.
• Serum creatinine < 2.0 mg/dL
• Able to provide informed written consent

Exclusion Criteria

• Other groups/forms of pulmonary hypertension (i.e. groups 2-5)
• Contraindicated to undergo fluoroscopy and/or coronary angiography
• Pregnancy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
PIMR change from baseline	Baseline, 6 months only if repeat RHC as standard of care	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.
PAH hospitalization or all-cause mortality at 1 year	1 year	The primary outcome is the composite of PAH hospitalization or all-cause mortality at 1 year.
RV-IMR	Baseline	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.

Trial Locations

Locations (1)

Ronald Reagan UCLA Medical Center; 🇺🇸 Los Angeles, California, United States