HRV as a Marker of Treatment Response in PAH Arterial Hypertension

Heart Rate Variability (HRV) as a Marker of Treatment Response in Pulmonary Arterial Hypertension (PAH)

This is a prospective longitudinal cohort study to determine the value of HRV obtained using noninvasive actigraphy to quantify the response to pulmonary vasodilator therapy in newly diagnosed PAH patients

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Other: Noninvasive actigraphy monitor

Detailed Description

This single center prospective longitudinal cohort study will take place at the University of Cincinnati (UC). We will screen adult patients newly diagnosed with PAH and placed on targeted pulmonary vasodilator therapy by their treating physician for enrollment.

We will enroll 35 eligible participants over a two-year period. HRV will be measured using the Polar™ H10 wearable chest actigraphy device in conjunction with analytic software to capture HRV data.

After enrollment and completion of the baseline visit, study participants will receive chest actigraphy device to measure their heart rate for a two hour period twice a week during study participation. Follow up research visits will be conducted at one-month, 3-months, and 6-months to sync the actigraphy device and assess any AE's.

In-between these visits, study staff will communicate with participants at two weeks, two months, 4 months, and 5 months, to identify and address any issues with study actigraphic device, assess any adverse events and maintain regular contact with study participants.

Throughout study participation, subjects will continue routine clinical care at the direction of their treating physician as needed.

• Study Type: Observational
• Enrollment (Estimated): 35

Contacts and Locations

• Study Contact: Name: Susan McMahan, BSN, RN, CCRP; Phone Number: 513-558-4376; Email: susan.mcmahan@uc.edu

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati
      • Contact: Arun Jose, MD, MS; Phone Number: 513-558-7451; Email: josean@ucmail.uc.edu
      • Contact: Susan Sellers, BSN, CCRP; Phone Number: 513-558-4376; Email: susan.mcmahan@uc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients seen at the University of Cincinnati PAH Clinic in Cincinnati, Ohio

Description

Inclusion Criteria:

• All adult patients (ages 18-70) of any functional class with a new diagnosis of PAH (World health Organization Group 1) placed on targeted therapy
• Eligible PAH etiologies include idiopathic PAH, associated with connective tissue disease, human immunodeficiency virus, hereditary, or portopulmonary hypertension
• Right heart catheterization (RHC) hemodynamics with a mean pulmonary arterial pressure >=20 millimetres of mercury at rest, a pulmonary capillary wedge pressure <= 15 millimetres of mercury, and a pulmonary vascular resistance >= 3 woods units

Exclusion Criteria:

• Inability to undergo (non-contrast) Magnetic Resonance Imaging (MRI) testing
• On chronotropic agents (Beta-Blockers, anti-arrhythmic medications, etc.) that could affect the calculation and interpretation of HRV measures
• Conditions that could affect the accuracy of MRI imaging, including a history previously repaired or unrepaired congenital heart defects, ventricular or atrial septal defects, or other anatomic cardiac abnormalities)
• Inability to complete a six-minute walk test
• Currently being on targeted PAH therapy at the time of consent and enrollment
• Thyroid disease, known arrhythmias in the past six months, uncontrolled anemia with a hemoglobin less than 7 grams per deciliter, untreated coronary artery disease or a diagnosis of myocardial infarction in the past 6 months, the presence of a cardiac pacemaker
• Clinically significant lung disease (including pulmonary function testing forced vital capacity < 60%), a positive ventilation/perfusion scan, uncontrolled sleep apnea not adherent with noninvasive positive pressure ventilation
• Unable to consent, pregnant women, and prisoners.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in HRV via RMSSD	Change from baseline in Root Mean Squared Successive Differences (RMSSD) measure of Heart Rate variability in patients on targeted therapy	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in HRV via SDNN	Change from baseline in Standard Deviation of N-to-N (SDNN) measure of Heart Rate Variability in patients on targeted therapy	6 months
Correlation with Cardiac Magnetic Resonance Imaging Variables	Correlation between RMSSD and SDNN with key cardiac Magnetic Resonance Imaging Variables of PAH disease, the Right Ventricular Stroke Volume	6 months
Correlation with NTproBNP	Correlation between RMSSD and SDNN with N-terminal Pro-B-Type Natriuretic Peptide (NTproBNP), a marker of PAH disease severity and treatment response	6 months
Correlation with REVEAL 2.0 Risk Score	Correlation between RMSSD and SDNN with the REVEAL 2.0 Risk score, a measure of PAH prognosis	6 months
Correlation with CAMPHOR Quality of Life Score	Correlation between RMSSD and SDNN with the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) score, a 3-domain quality of life assessment tool specific to PAH patients	6 months

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Investigators: Principal Investigator: Arun Jose, MD, MS, University of Cincinnati

Publications and helpful links

General Publications

• Heresi GA, Dweik RA. Strengths and limitations of the six-minute-walk test: a model biomarker study in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 May 1;183(9):1122-4. doi: 10.1164/rccm.201012-2079ED. No abstract available.
• Ulrich S, Fischler M, Speich R, Bloch KE. Wrist actigraphy predicts outcome in patients with pulmonary hypertension. Respiration. 2013;86(1):45-51. doi: 10.1159/000342351. Epub 2012 Dec 11.
• Pugh ME, Buchowski MS, Robbins IM, Newman JH, Hemnes AR. Physical activity limitation as measured by accelerometry in pulmonary arterial hypertension. Chest. 2012 Dec;142(6):1391-1398. doi: 10.1378/chest.12-0150.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: June 25, 2020
• First Submitted That Met QC Criteria: June 25, 2020
• First Posted (Actual): June 30, 2020

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: 2019-1371

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