Raising pacemaker heart rate during light exercise to lower left-heart pressures in HFpEF

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

This test will try whether temporarily increasing the heart rate by adjusting pacemaker settings during light exercise can lower left-heart filling pressures and improve cardiac output in people with HFpEF who already have a DDD pacemaker.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Universitaire Ziekenhuizen KU Leuven (other)
• Locations: 2 sites (Hasselt and 1 other locations)
• Trial ID: NCT07270536 on ClinicalTrials.gov

What this trial studies

Adults with HFpEF who have a DDD pacemaker will undergo a single on-site invasive hemodynamic test while pedaling a light stationary bike. A venous and arterial catheter will measure intracardiac pressures and blood oxygen while the pacemaker heart rate is increased in three steps and the AV delay is optimized. Measurements at each step will be used to identify the heart rate associated with the lowest filling pressures and to calculate cardiac output. The visit lasts about three hours and the protocol plans to enroll 20 patients from Leuven and Hasselt.

Who should consider this trial

Good fit: Ideal candidates are adults with HFpEF in sinus rhythm who have had a DDD pacemaker with left bundle branch area pacing implanted at least 12 weeks prior and are on optimized HFpEF therapy.

Not a fit: Patients without a compatible pacemaker, with atrial arrhythmias, significant pulmonary comorbidity, or who cannot undergo invasive catheter testing are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, this approach could provide a non-drug way to reduce exercise-related left-heart pressures and potentially improve exercise capacity by reprogramming an existing pacemaker.

How similar studies have performed: Small physiologic studies and case reports suggest heart-rate modulation can lower filling pressures, but using pacemaker-driven accelerated pacing in HFpEF remains largely experimental.

Eligibility criteria

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. HFA-PEFF score \>= 5 or
   2. H2FPEF score \>= 6 or
   3. EF \>= 50% and

   i. 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), 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. Episode of atrial fibrillation in the last 3 months
   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

Where this trial is running

Hasselt and 1 other locations

• Jessa Ziekenhuis Hasselt — Hasselt, Belgium (RECRUITING)
• University Hospitals Leuven — Leuven, Belgium (RECRUITING)

Study contacts

• Study coordinator: Margot Vermeiren, MD

Conditions: HFpEF, Heart Failure with Preserved Ejection Fraction, Accelerated pacing, Chronotropic response, Hemodynamics