Novel Index (PIMR) in PAH

Study Overview
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Brief Summary
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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.

Official Title
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Impact of the Pulmonary Index of Microcirculatory Resistance in Pulmonary Arterial Hypertension

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Other: Pulmonary Index of Microcirculatory Resistance
* Other: Right Ventricle Index of Microcirculatory Resistance


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PAH Patients<br>Pulmonary Index of Microcirculatory Resistance (PIMR) and Right Ventricle Index of Microcirculatory Resistance (RV-IMR) measurements during standard-of-care right +/- left heart catheterization at baseline and among those who undergo a standard-of-care right heart catheterization at 6 months. | Other: Pulmonary Index of Microcirculatory Resistance<br>* PIMR measurement involves placing a coronary pressure wire in the pulmonary arteries and making pressure/time measurements during maximal flow down the artery.<br>* Other names: PIMR;Other: Right Ventricle Index of Microcirculatory Resistance<br>* 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.<br>* Other names: RV-IMR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PAH hospitalization or all-cause mortality at 1 year | The primary outcome is the composite of PAH hospitalization or all-cause mortality at 1 year. | 1 year | 
| PIMR change from baseline | 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, 6 months only if repeat RHC as standard of care | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Hypertension, Pulmonary Index of Microcirculatory Resistance, Pulmonary Arterial Hypertension, Index of Microcirculatory Resistance