Clinical trial NCT06467266: Mechanistic Insights From Temporary Pacing in HFpEF
Official title: Mechanistic Insights From Multisite Pacing in Patients With Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Heart Failure Preserved Ejection Fraction
Pacing
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
First posted: 2024-06-20
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an observational cohort mechanistic study.
Primary purpose: BASIC_SCIENCE

Brief summary: Heart failure with preserved ejection fraction (HFpEF) is characterised by impaired diastolic function. A recent clinical trial has demonstrated multiple beneficial outcomes in HFpEF patients receiving personalised accelerated pacing from indwelling permanent pacemakers, including symptomatic improvement, objective reductions in NT-proBNP level and AF-burden.

The investigators aim to determine the underlying mechanisms behind these documented effects, to investigate the acute intracardiac haemodynamic response to temporary multisite pacing in HFpEF participants and to gain further mechanistic insight with additional haemodynamic, electrical and echocardiographic data collection during temporary pacing in this cohort. This will all provide valuable information towards new potential targets of therapy.

Detailed description: In this research study, the investigators will perform a one-off temporary pacing procedure in the catheter lab at St Thomas' Hospital in patients with heart failure with preserved ejection fraction (HFpEF). During the short procedure, the investigators will pace the heart at different heart rates and from different parts of the heart. The investigators will measure the change in pressure inside the heart in response to each pacing site/mode and rate. Altogether, the investigators aim to find out how different pacing modes and heart rates impact how well the heart fills and pumps in HFpEF.

The study will provide valuable information about the underlying mechanisms of pacing in HFpEF, which could significantly influence the future direction of HFpEF management. Specifically, it will help the investigators to understand what types of pacemaker and pacing site or pacing mode may be chosen in HFpEF patients requiring pacing, which accounts for around 20% of all HFpEF patients.

Eligibility criteria: Inclusion Criteria:

* Participant is willing and able to give informed consent for participation in the study.
* Male or Female, aged 18 years or above.
* Formal diagnosis of HFpEF as per ESC guidelines
* NYHA grade II-IV heart failure symptoms
* LVEF ≥50%
* Female participants of child-bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter
* Able (in the Investigators opinion) and willing to comply with all study requirements.
* Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.

Exclusion Criteria:

* History of persistent or permanent AF
* Permanent pacing device in situ
* Female participants who are pregnant, lactating or planning pregnancy during the course of the study.
* Scheduled elective surgery or other procedures requiring general anaesthesia during the study.
* Participant who is terminally ill
* Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
* Significant peripheral vascular disease precluding an EP study
* A contraindication to anticoagulation
* A prosthetic aortic, mitral or tricuspid valve
* Significant Aortic valve disease
* Known LV thrombus
* Insufficient capacity to consent to the study
* Participation in other studies with active treatment / investigational arm to avoid bias

Primary outcomes:
measure: Number of participants with changes in left ventricular end diastolic pressure upon accelerated right atrial pacing and conduction system pacing
timeFrame: 30 months
Secondary outcomes:
measure: Number of participants with leftward, downward shift in the LV P-V loop during accelerated RA pacing and CSP, not reproduced by RV pacing
timeFrame: 30 months
measure: Number of participants with changes in Echo measures of diastology upon right atrial pacing and conduction system pacing
timeFrame: 30 months
Other outcomes:
Locations:
Study officials:
References:
citation: Infeld M, Wahlberg K, Cicero J, Plante TB, Meagher S, Novelli A, Habel N, Krishnan AM, Silverman DN, LeWinter MM, Lustgarten DL, Meyer M. Effect of Personalized Accelerated Pacing on Quality of Life, Physical Activity, and Atrial Fibrillation in Patients With Preclinical and Overt Heart Failure With Preserved Ejection Fraction: The myPACE Randomized Clinical Trial. JAMA Cardiol. 2023 Mar 1;8(3):213-221. doi: 10.1001/jamacardio.2022.5320.
citation: McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.
citation: Reddy YNV, Koepp KE, Carter R, Win S, Jain CC, Olson TP, Johnson BD, Rea R, Redfield MM, Borlaug BA. Rate-Adaptive Atrial Pacing for Heart Failure With Preserved Ejection Fraction: The RAPID-HF Randomized Clinical Trial. JAMA. 2023 Mar 14;329(10):801-809. doi: 10.1001/jama.2023.0675.
citation: Elliott MK, Strocchi M, Sieniewicz BJ, Sidhu B, Mehta V, Wijesuriya N, Behar JM, Thorpe A, Martic D, Wong T, Niederer S, Rinaldi CA. Biventricular endocardial pacing and left bundle branch area pacing for cardiac resynchronization: Mechanistic insights from electrocardiographic imaging, acute hemodynamic response, and magnetic resonance imaging. Heart Rhythm. 2023 Feb;20(2):207-216. doi: 10.1016/j.hrthm.2022.10.019. Epub 2022 Oct 28.
citation: Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2017 Oct;14(10):591-602. doi: 10.1038/nrcardio.2017.65. Epub 2017 May 11.