Arterial Stiffness and Endothelial Function in Heart Failure (ASEF-HF)

Pathophysiology of Heart Failure: the Role of Arterial Stiffness and Endothelial Function

Heart Failure (HF) is a global condition affecting at least 26 million people worldwide. Despite advances in treatment, HF patients continue to experience poor health outcomes. This study aims to improve understanding of the role of blood vessels in people with heart failure.

The study will assess how arterial stiffness (how stiff blood vessels are) and endothelial function (how well the lining of blood vessels functions) change over time and respond to treatments received as part of routine clinical care. Blood vessel function and heart performance will be assessed at three time points:

• At baseline (when Patients are first diagnosed with heart failure).
• After completing 4 ± 2 weeks of heart-failure medicines prescribed to patients as part of their routine clinical care.
• After completion of cardiac rehabilitation program as a part of their routine clinical care.

All assessments are non-invasive.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Other: Study Assessment

Detailed Description

This study is designed as an observational pilot study involving 50 patients (age ≥ 18 years) with a new diagnosis of HF (HFpEF or HFrEF). It is sponsored by Coventry University but will take place at The Cardiology and Cardiac Rehabilitation Departments at University Hospital Coventry and Warwickshire (study site). All study assessments will be scheduled to coincide with participants' routine clinical appointments, ensuring no additional hospital visits are required solely for research purposes.

The study will involve participants attending the clinical research site for three study visits lasting approximately 1.5 hours each:

(i) Visit 1: Baseline visit- at the point of diagnosis. (ii) Visit 2: After completion of initial pharmacologic treatment for HF (usually around 4±2 weeks).

(iii) Visit 3: After completion of cardiac rehabilitation - delivered as part of standard care for HF patients (another 4±2 weeks)

The following assessments will be performed as part of this study:

Baseline (only):

• Collection of demographic details (age, sex, ethnicity, alcohol consumption, and smoking status)
• Collection of previous/existing results from the participants medical records will include the following:
• Medical History: Documented diagnoses, comorbidities, and history of cardiovascular conditions.
• Concomitant Medications: Details of all current prescribed and over-the-counter medications relevant to their clinical care.
• Physical Examination and Vital Signs: Blood pressure, pulse rate, and any other routinely recorded cardiovascular parameters available within their clinical record.

All data will be collected only from information already recorded as part of routine clinical care.

Baseline (Week 0), Visit 2 (Week 4 ± 2), Visit 3 (Week 4 ± 2)

The participant will undergo the study assessments as described below:

Participant will undergo physical examination (Blood pressure and Pulse) and anthropometrics (Body weight, height, and body mass index (BMI)) at each visit.

1. Arterial stiffness, as a measure of arterial function, will be assessed using the non-invasive SphygmoCor device (AtCor Medical Ltd., Australia), which allows for both pulse wave analysis and pulse wave velocity to be performed non-invasively using the gold standard techniques. The measurement is simple and painless, taking only a few minutes to perform. While the participant is in a comfortable supine position, the researcher will place a tonometer (pencil-like sensor) gently against the wrist and will record blood pressure signal from the pulse.
2. Endothelial function, as a measure of vascular health, will be assessed using non-invasive Laser Doppler Flowmetry (LDF) technique, which measures cutaneous microvascular blood flow according to the Fizeau-Doppler principle. Measurements of cutaneous blood flow will be expressed in perfusion units and the Laser Doppler signal will be continuously monitored on a computer (Moor instruments, VMS software V.4.06) coupled with Moor instruments system (moorVMS-VASC). The thenar eminence will be used for the placement of the LDF probe (VP1T/7), consistently at the same place, before and post the occlusive reactive hyperaemia manoeuvre. The room temperature will be maintained at 22°C during forearm cutaneous blood flow measurements. Reactive hyperaemia will be produced by occluding the forearm blood flow with a pneumatic cuff inflated to a pressure of 50 mm Hg above the Systolic blood pressure for 3 min. The signal obtained during complete forearm arterial occlusion will be used to determine the biological zero for cutaneous blood flow. Baseline (resting) flow will be calculated as the average of a stable 6-minute Laser Doppler Flowmetry recording obtained prior to cuff occlusion.
3. Haemodynamic monitoring and Cardiac Output Response to Stress (CORS) test Participants will then be connected to the bioreactance Non-Invasive Cardiac Output Monitor (StarlingSV, Baxter Inc., UK) which we have previously evaluated. The method uses four pairs of electrodes applied at the front side of the upper and lower thorax (similar to ECG). Bioreactance is a novel method for continuous non-invasive cardiac function monitoring and estimates cardiac output by analysing the frequency of relative phase shift of electronic current delivered across the thorax. Measurements will be performed using the protocol we have recently developed. Cardiac output will be evaluated whilst participants are lying on their back with their legs elevated at 45 degrees. This is called passive leg raise assessment. The CORS test will also be performed consisting of three phases: 3-min rest (supine) phase, 3-min challenge (standing) phase, and 3-min stress (exercise step-test) phase.
4. Voice recording Subtle changes in speech pattern have emerged as a tool to risk stratify, diagnose, and monitor cardiovascular conditions. Participants will be seated in a quiet room in the clinical research facility to complete the recording. Participants' voices will be audio recorded for up to five minutes while they read a standardised text aloud, speak freely for a short time, count out loud, and then say specific sounds. The recorder will be started just before patients start to read the text and stopped at the end of the task. Voice will be recorded on a standard digital recorder. However, recordings will be transferred immediately to a secure University owned server as per Coventry University ethics guidelines and procedures and then deleted from the recorder device. The software extracts relevant voice features after low-level acoustic features and sudden impulsive noise have been removed using spectral noise gating and voice processing techniques. Extracted voice features are presented in numerical values and will be stored in a password protected computer for further analysis using machine learning and artificial intelligence.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Djordje Jakovljevic; Phone Number: 07522694321; Email: djordje.jakovljevic@coventry.ac.uk
• Study Contact Backup: Name: Prithwish Banerjee, MBBS, Dip Card, MD, MRCP, FES; Phone Number: 07803711713; Email: Prithwish.Banerjee@uhcw.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Potential participants will be identified through the Heart failure service at University Hospitals Coventry & Warwickshire. Members of the patient's existing direct clinical care team will review clinic lists and the participant's medical history to identify potentially eligible patients.

Description

Inclusion Criteria:

• Male and female ≥ 18 years old.

  • Have a confirmed de-novo diagnosis of Heart failure with preserved ejection fraction or Heart failure with reserved ejection fraction. Common HF phenotypes (e.g., hypertension, diabetes, obesity) will be recorded as part of routine baseline data but will not influence recruitment or sampling. .
  • Have stable Heart failure in the opinion of the investigator.
  • Have ability, in the opinion of the investigator, to participate in study activities.
  • Able to provide written informed consent.

Exclusion Criteria:

• • Inability to provide verbal informed consent.

  • Presenting with severe symptoms; major co-morbidity or other alternative diagnoses (e.g., malignancy, severe respiratory disease, severe mental health problem/s).
  • Recent acute coronary syndrome (within 60 days).
  • Severe physical disability preventing independence.
  • Severe renal insufficiency.
  • Pregnancy (Present or planned).
  • Life expectancy less than 12 months

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Heart failure with preserved ejection fraction	Other: Study Assessment; Collection of demographic details (age, sex, ethnicity, alcohol consumption, and smoking status); Collection of previous/existing results from the participants medical records will include the following:; Medical History: Documented diagnoses, comorbidities, and history of cardiovascular conditions.; Concomitant Medications: Details of all current prescribed and over-the-counter medications relevant to their clinical care.; Physical Examination and Vital Signs: Blood pressure, pulse rate, and any other routinely recorded cardiovascular parameters available within their clinical record. All data will be collected only from information already recorded as part of routine clinical care. In addition to these, the participant will undergo the study assessments: Arterial stiffness, endothelial function, Cardiac output response to stress test and Voice recognition.
Heart Failure with reserved ejection fraction	Other: Study Assessment; Collection of demographic details (age, sex, ethnicity, alcohol consumption, and smoking status); Collection of previous/existing results from the participants medical records will include the following:; Medical History: Documented diagnoses, comorbidities, and history of cardiovascular conditions.; Concomitant Medications: Details of all current prescribed and over-the-counter medications relevant to their clinical care.; Physical Examination and Vital Signs: Blood pressure, pulse rate, and any other routinely recorded cardiovascular parameters available within their clinical record. All data will be collected only from information already recorded as part of routine clinical care. In addition to these, the participant will undergo the study assessments: Arterial stiffness, endothelial function, Cardiac output response to stress test and Voice recognition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Arterial stiffness measured by Pulse wave velocity (PWV) using SphygmoCor	Change in arterial stiffness measured using pulse wave velocity (PWV) obtained with the SphygmoCor device from baseline to completion of pharmacological treatment and cardiac rehabilitation.	Up to 12 week
Change in Endothelial Function Measured by Laser Doppler Flowmetry (LDF)	Change in endothelial function measured using Laser Doppler Flowmetry from baseline to completion of pharmacological treatment and cardiac rehabilitation.	Up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cardiac Output Measured Using the Cardiac Output Response to Stress (CORS) Test	Change in cardiac output measured during the Cardiac Output Response to Stress (CORS) test from baseline to completion of cardiac rehabilitation..	Up to 12 weeks
Change in Voice-derived Biomarkers Obtained From Voice Recordings	Change in voice-related parameters derived from digital voice recordings from baseline to completion of cardiac rehabilitation.	Up to 12 weeks

Collaborators and Investigators

• Sponsor: Coventry University
• Investigators: Principal Investigator: Prithwish Banerjee, University Hospitals Coventry & Warwickshire NHS Trust

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: July 3, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 20, 2026

Study Record Updates

• Last Update Posted (Actual): July 20, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Endothelial Function; Heart failure; Arterial stiffness
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Health Services Administration; Health Care Quality, Access, and Evaluation; Health Care Evaluation Mechanisms; Quality of Health Care; Outcome and Process Assessment, Health Care; Outcome Assessment, Health Care
• Other Study ID Numbers: P185795

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The Sponsor has not yet made a final decision regarding the sharing of individual participant data (IPD). Any future data sharing will be considered in accordance with participant consent, UK GDPR requirements, Coventry University policies, and applicable regulatory guidance.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No