Non-Invasive Measurement of Cardiac Output and Stroke Volume in PAH/CTEPH

Study Overview
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Brief Summary
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Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are severe clinical conditions that, despite advances in therapeutics over the past 20 years, lead to serious morbidity and mortality. Guidelines on the diagnosis and treatment of pulmonary hypertension (PH) recommend the use of a multiparametric risk stratification tool to determine severity of disease, which should guide initial therapy and therapy modulation. This multiparametric risk stratification schema includes objective assessment of exercise capacity, right ventricular function and hemodynamic parameters in order to classify patients into severity categories. Cardiac index (CI) and right atrial pressure (RAP), measured via right heart catheterization (RHC), are the hemodynamic parameters used in risk assessment of PH. Arguably, stroke volume index (SVI) is the most important hemodynamic parameter for assessment of PH severity and there is currently no validated method for noninvasive measurement of cardiac output (CO), CI or SVI. Currently, a major obstacle in the field is that hemodynamic measurements are not obtained on a regular basis in the risk assessment and therapy modulation of patients with PAH and CTEPH. If a noninvasive method of hemodynamic measurement could be correlated with other objective measurements of risk assessment, it could become an invaluable tool in therapy initiation and modulation in the ambulatory setting. This is a single center study to evaluate the use of non-invasive measurement of CO and stroke volume to assess risk and response to treatment in patients with PAH and non- operable CTEPH. We anticipate to enroll a total of 100 subjects at Ronald Reagan UCLA Medical Center. A maximum of 10 hour in total for the study including the consent process, pre-procedure care, RHC procedure, and follow up visit. The initial visit will be approximately 4 hours with the RHC procedure itself will only be 20 minutes. Each follow up visit will be 1.5 hour. Patients with known or suspected PAH or CTEPH will undergo a RHC as part of his or her standard of care. Three techniques of CO measurement will be performed sequentially at the time of the RHC. The device that will be used is the Edwards ClearSight system and EV1000 clinical platform, a device that measures NIBP. Patients will be followed over the period of 1 year every 3 months to obtain serial measurements for six-minute walk distance (6MWD), World Health Organization (WHO)/New York Heart Association Functional Class (FC), B-type natriuretic peptide (BNP) or N-terminal-pro hormone BNP (NT-proBNP), and non-invasive hemodynamic measurements. Additional visits will be scheduled to obtain the serial measurements one month prior and one month following if a patient is initiating or changing PH-specific therapy. As this is a study looking at the feasibility of non-invasive measurement of cardiac output and stroke volume for risk assessment and response to therapy in pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH), study personnel performing the study procedures will not be blinded to the clinical diagnosis and the management of the subject.

Detailed Description
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This is a single center study to evaluate the use of non-invasive measurement of cardiac output and stroke volume to assess risk and response to treatment in patients with pulmonary arterial hypertension (PAH) and non- operable chronic thromboembolic pulmonary hypertension (CTEPH). We anticipate to enroll a total of 100 subjects at Ronald Reagan UCLA Medical Center. After informed consent is obtained, the following procedure will be performed: Patients with known or suspected pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) will undergo a right heart catheterization (RHC) as part of his or her standard of care. Three techniques of cardiac output (CO) measurement will be performed sequentially at the time of the RHC. The order of cardiac output testing will be randomized after informed consent is obtained and prior to the procedure. The operator performing the RHC procedure will be blinded to both the non-invasive blood pressure (NIBP) measurement and direct Fick cardiac output (CO) measurements while performing thermodilution cardiac output (CO) measurement. The device that will be used is the Edwards ClearSight system and EV1000 clinical platform, a device that measures non-invasive blood pressure (NIBP). Patients will be followed over the period of 1 year, up to every 3 months, to obtain serial measurements of six-minute walk distance (6MWD), World Health Organization (WHO)/New York Heart Association Functional Class (FC), and B-type natriuretic peptide (BNP) or N-terminal-pro hormone BNP (NT-proBNP) as part of standard of care. These serial measurements will be collected from the patient's medical record. Non-invasive hemodynamic measurements will be performed for research purposes. Additional visits will be scheduled to obtain the serial measurements one month prior and one month following if a patient is initiating or changing PH-specific therapy. As this is a study looking at the feasibility of non-invasive measurement of cardiac output and stroke volume for risk assessment and response to therapy in pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH), study personnel performing the study procedures will not be blinded to the clinical diagnosis and the management of the subject.

Official Title
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Use of Non-invasive Measurement of Cardiac Output and Stroke Volume to Assess Risk and Response to Treatment in Patients With PAH or CTEPH

Conditions
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Pulmonary Arterial Hypertension, Chronic Thromboembolic Pulmonary Hypertension

Intervention / Treatment
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* Device: Non-invasive hemodynamic measurements


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient ≥ 18 years of age. The patient must understand and sign informed consent form (ICF). Patients with a confirmed diagnosis or suspected diagnosis of pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) prior to initiation or change in therapy. PAH or CTEPH patients undergoing right heart catheterization (RHC) as part of their standard of care. Exclusion Criteria: BMI < 20 or BMI > 35. Height less than 120 cm. Diagnosis of atrial fibrillation, aortic or mitral valve insufficiency or stenosis, or end-stage renal disease.

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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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: This is a single center study to evaluate the use of non-invasive measurement of cardiac output and stroke volume to assess risk and response to treatment in patients with pulmonary arterial hypertension (PAH) and non- operable chronic thromboembolic pulmonary hypertension (CTEPH). We anticipate to enroll a total of 100 subjects at Ronald Reagan UCLA Medical Center.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients diagnosed with PAH or CTEPH<br>Patients with a confirmed diagnosis or suspected diagnosis of pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) prior to initiation or change in therapy. | Device: Non-invasive hemodynamic measurements<br>* A patient profile will be set up in the Edwards EV1000 clinical platform by inputting the patient's demographic information. One or two Edwards ClearSight finger cuffs will be placed on the index, middle, and/or ring finger on one hand of the patient. A pressure controller will be secured by a forearm strap where the finger cuffs will be connected to the pressure controller. The pressure controller will be connected to the Edwards EV1000 clinical platform monitor. A heart reference sensor (HRS) will be connected to the pressure controller, a finger cuff, and to the patient at heart level. The Edwards EV1000 clinical platform will calibrate the finger probes, then record measurements for 10-30 seconds. If two finger probes are available, measurements will alternate between fingers.<br>* Other names: Non-invasive blood pressure (NIBP);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| stroke volume (SV) | Stroke Volume (SV) is the volume of blood in millilitres ejected from the each ventricle due to the contraction of the heart muscle which compresses these ventricles. | 12 months | 
| stroke volume index (SVI) | Stroke Volume Index (SVI) relates SV to body surface area (BSA), thus relating heart performance to the size of the individual. The unit of measurement is millilitres per square metre (ml/m2). | 12 months | 
| cardiac output (CO) | Cardiac Output (CO) is the amount of blood the heart pumps from each ventricle per minute. It is usually expressed in litres per minute (L/min). | 12 months | 
| cardiac index (CI) | Cardiac index (CI) is the cardiac output proportional to the body surface area (BSA). The unit of measurement is litres per minute per square metre (L/min/m2). | 12 months | 
| systemic vascular resistance (SVR) | Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature. The units for SVR are most commonly expressed as pressure (mmHg) divided by cardiac output (mL/min), or mmHg⋅min⋅mL^-1 | 12 months | 
| blood pressure (BP) | The pressure of the blood in the circulatory system, often measured for diagnosis since it is closely related to the force and rate of the heartbeat and the diameter and elasticity of the arterial walls. Systolic Blood Pressure in mmHg Diastolic Blood Pressure in mmHg | 12 months | 
| heart rate (HR) | The number of heartbeats per unit of time, usually per minute. Measured in beats per minute (BPM) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| six-minute walk distance (6MWD) | The distance covered over a time of 6 minutes. This is used as the outcome by which to compare changes in performance capacity. | 12 months | 
| B-type natriuretic peptide (BNP) or N-terminal-pro hormone BNP (NT-proBNP) | B-type natriuretic peptide (BNP) is a hormone produced by your heart. N-terminal (NT)-pro hormone BNP (NT-proBNP) is a non-active prohormone that is released from the same molecule that produces BNP. Both BNP and NT-proBNP are released in response to changes in pressure inside the heart. These changes can be related to heart failure and other cardiac problems. Levels goes up when heart failure develops or gets worse, and levels goes down when heart failure is stable. | 12 months | 
| World Health Organization (WHO)/New York Heart Association Functional Class (FC) | The World Health Organization functional classification (WHO-FC) is a tool used to measure disease severity in patients with PAH whereby health care providers (HCPs) use patient reports of symptom experience and activity limitations to make their assessment. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-invasive Hemodynamics, Non-invasive Blood Pressure, Pulmonary Arterial Hypertension, Chronic Thromboembolic Pulmonary Hypertension, PAH, CTEPH