Accelerated Pacing and Cardiac Filling Pressures During Exercise in Patients With Heart Failure With Preserved Ejection Fraction (APAVE)

The Impact of Accelerated Pacing and AV-delay Regulation on the Pulmonary Capillary Wedge Pressure During Exercise in Patients With HFpEF

What is HFpEF? In heart failure with preserved ejection fraction (HFpEF), the heart pumps well but struggles to relax and fill with blood between beats. This raises the pressure inside the heart, especially during physical activity, causing symptoms like shortness of breath and fatigue - even with light activities like walking or climbing stairs.

What is this study about? Recent research suggests that a higher heart rate may help lower this elevated pressure. Many HFpEF patients already have a pacemaker. This study investigates whether simply increasing the pacemaker rate during light exercise can reduce the pressure in the heart.

How does the study work? We wille measure heart pressures in 20 patients in rest and while cycling using a heart catheter and monitor their breathing. Throughout these measurements, we will gradually increase the pacemaker rate step by step.

Why does this matter? If a higher pacemaker rate successfully lowers heart pressure, this could offer a simple, drug-free way to improve daily functioning and comfort for thousands of patients with HFpEF, justifying further long-term studies to evaluate effects beyond the immediate changes in heart pressures.

Study Overview

• Status: Recruiting
• Conditions: HFpEF
• Intervention / Treatment: Other: Accelerated pacing with AV-delay optimization during rest and light intensity cycling

Detailed Description

First, we will review patient records to identify eligible participants, who will then be contacted during their regular check-up visit. If they are interested in participating, they will be invited for an additional screening visit if needed.

Patients who meet the eligibility criteria will be invited for an invasive exercise test. At this visit, two small tubes (catheters) will be placed, one in a neck vein and one in a wrist artery, to measure heart pressures and blood oxygen levels. The patient then sits on a reclined stationary bike, wearing a breathing mask to monitor oxygen uptake. Throughout the visit, ultrasound measurements of the heart will also be performed.

First, heart pressures are measured at rest while the pacemaker rate is gradually increased in three steps (+20, +40, +60 beats per minute). Second, the patient cycles gently while the same measurements are repeated, with the pacemaker rate increased in three steps (+10, +30, +50 beats per minute). In a final step of both the rest and exercise protocol, the heart rate will return to the level associated with the lowest heart pressure, and blood oxygen levels will be checked, allowing the research team to calculate how many liters of blood the heart pumps per minute. Afterward, the catheters are safely removed and the pacemaker settings are restored to their original values. This visit is expected to last about three hours, after which study participation ends.

The full study is expected to be completed once 20 patients have finished all study tests.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Margot Vermeiren, MD; Phone Number: +3216332211; Email: margot.vermeiren@kuleuven.be

Study Locations

• Belgium
  • Hasselt, Belgium, 3500
    • Recruiting
    • Jessa Ziekenhuis Hasselt
    • Contact: Jan Verwerft, MD PhD; Email: jan.verwerft@jessazh.be
    • Principal Investigator: Jan Verwerft, MD PhD
  • Leuven, Belgium, 3000
    • Recruiting
    • University Hospitals Leuven
    • Contact: Margot Vermeiren, MD; Phone Number: +3216332211; Email: margot.vermeiren@kuleuven.be
    • Contact: Email: margotvermeiren97@gmail.com
    • Sub-Investigator: Margot Vermeiren, MD
    • Principal Investigator: Peter Sinnaeve, MD PhD
    • Sub-Investigator: Tim Van Puyvelde, MD
    • Sub-Investigator: Youri Bekhuis, MD
    • Sub-Investigator: Rik Willems, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Participants eligible for inclusion in this study must meet all of the following criteria:

1. Voluntary written informed consent of the participant has been obtained prior to any screening procedures
2. At least 18 years of age at the time of signing the Informed Consent Form (ICF)

3. Heart failure with preserved ejection fraction, defined as one of the below criteria:

   1. EF >= 45% and HFA-PEFF score >= 5 (Heart Failure Association-Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology; heart failure association of the European Society of Cardiology and the Heart Failure Association (34))
   2. EF >= 45% and H2FPEF score >= 6 (Heavy, Hypertensive, Atrial fibrillation, Pulmonary hypertension, Elder, Filling pressure; Mayo Clinic group (35)))
   3. EF >= 45% and

   i. History of heart failure hospitalization after pacemaker implantation or ii.On loop-diuretics at time of inclusion

4. Having a DDD-pacemaker with LBB area pacing, implanted at least 12 weeks before iCPET
5. >=6 weeks on optimal HFpEF therapy (MRA and SGLT2i) at time of iCPET, unless contraindicated or not tolerated
6. Sinus rhythm at time of screening and iCPET

Participants eligible for this Study must not meet any of the following criteria:

1. Participant has a history of:

   1. Evidence of significant pulmonary comorbidity based on abnormal pulmonary function tests (FEV1 <60%) or aberrant lung parenchyma more than mild on radiological imaging
   2. Severe/symptomatic valvular diseases
   3. Severe pulmonary hypertension (PASP > 55mmHg estimated by Doppler Echo)
   4. Unstable arrhythmias (VT, VF)
   5. Recurrent syncopes after pacemaker implantation
   6. Permanent atrial fibrillation
   7. Amyloid cardiomyopathy
2. Physical inability to perform exercise
3. More than 1 hospitalization for heart failure in the last year
4. Resting heart rate> 100bpm
5. At time of iCPET or inclusion: decompensated heart failure, unstable coronary syndrome

6. Contraindication to central venous access

   1. Severe coagulopathy (e.g., spontaneous INR > 2, thrombocytopenia < 50,000/µL)
   2. Local infection or skin infection at the insertion site
   3. Thrombosis or anatomical abnormalities of the right jugular vein
   4. Pneumothorax or contralateral lung pathology
   5. Inability to properly position the patient

7. Contraindication to arterial access

   1. Thrombosis or occlusion of the target artery
   2. Raynaud's phenomenon or other vasospastic disorders
   3. Active infection at the intended insertion site
   4. Severe coagulopathy (e.g., spontaneous INR > 2, thrombocytopenia < 50,000/µL)
   5. Insufficient collateral circulation (e.g., inadequate perfusion in an Allen test)

8. Contraindications to CPET

   1. ECG signifying myocardial injury
   2. ECG signifying current or potentially lethal arrhythmias
   3. Systemic hypotension (e.g. systolic blood pressure < 90 mmHg)
   4. Extreme hypertension (e.g. systolic blood pressure > 220 mmHg)
   5. Syncope, presyncope, or lightheadedness
   6. SaO2 < 88%
   7. Severely elevated PCWP (> 40 mmHg) during exercise

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: All patients

Other: Accelerated pacing with AV-delay optimization during rest and light intensity cycling; Patients will undergo one resting and one exercise protocol (25 Watts). During each protocol, the pacemaker rate will be gradually increased in three stages: +20, +40, +60 bpm at rest and +10, +30, +50 bpm during exercise. At each stage, intracardiac pressures and shear-wave velocity will be measured. In a final fourth stage, the pacemaker rate returns to the level associated with the lowest filling pressure, after which blood oxygen levels and oxygen uptake are assessed to calculate cardiac output.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary capillary wedge pressure (PCWP), measured using a Swan-Ganz catheter (pulmonary artery catheter).	The change in PCWP at each pacing frequency (+20 bpm, +40 bpm, +60 bpm) with its corresponding optimal AV-delay at rest, compared to baseline PCWP. The change in PCWP at each pacing frequency (+10 bpm, +30 bpm, +50 bpm) using dynamic AV-delay programming, while avoiding truncation, compared to baseline PCWP during exercise (cycle ergometry at 25 W) Baseline PCWP is calculated as the average of the measurements before and after each accelerated pacing-on step, using the intrinsic HR or baseline atrial pacing rate as the reference HR, as applicable	Intraprocedural

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac output, measured using the direct Fick principle	The change in CO, measured by the direct Fick principle, at the pacing frequency corresponding to the greatest reduction in PCWP compared to the reference HR at rest and during exercise (cycling at 25 Watts)	Intraprocedural
Shear wave velocity, measured via echocardiographically obtained myocardial shear waves following mitral valve closure	The change in shear wave velocity (SWV) at each pacing rate compared to the reference heart rate at rest and during exercise (cycling at 25 Watts) The shear wave velocity at the reference heart rate is defined as the average of the SWV at the reference heart rate heart rate before and after each pacing step.	Intraprocedural
Peripheral oxygen extraction	The change in peripheral oxygen extraction, measured by the oxygen uptake divided by the cardiac output, at the pacing frequency corresponding to the greatest reduction in pulmonary capillary wedge pressure compared to peripheral oxygen extraction at the reference heart rate at rest and during exercise (cycling at 25 Watts)	Intraprocedural
Stroke volume	The change in stroke volume, measured by the cardiac output divided by the heart rate, at the pacing frequency corresponding to the greatest reduction in pulmonary capillary wedge pressure compared to stroke volume at the reference heart rate at rest and during exercise (cycling at 25 Watts)	Intraprocedural

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: Hartcentrum Hasselt

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 25, 2025
• First Posted (Actual): December 8, 2025

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Hemodynamics; Heart Failure with Preserved Ejection Fraction; Chronotropic response; Accelerated pacing
• Other Study ID Numbers: S70922

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared due to privacy considerations and participant confidentiality.

Drug and device information, study documents

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