Mechanistic Insights From Temporary Pacing in HFpEF

NCT06467266 | Not Yet Recruiting

• 1 other identifier: 332571
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Heart Failure Preserved Ejection Fraction; Pacing

Outcome Measures

Primary Outcomes (1)

• Number of participants with changes in left ventricular end diastolic pressure upon accelerated right atrial pacing and conduction system pacing

  Measurement of the absolute left ventricular end diastolic pressure (in mmHg) and volume (in milliliter) at real-time during each pacing mode, heart rate and AV delay with a pressure volume loop catheter

  30 months

Secondary Outcomes (2)

• Number of participants with leftward, downward shift in the LV P-V loop during accelerated RA pacing and CSP, not reproduced by RV pacing

  30 months

• Number of participants with changes in Echo measures of diastology upon right atrial pacing and conduction system pacing

  30 months

Study Arms (1)

Intervention

EXPERIMENTAL

Patients will undergo cardiac imaging with a cardiac MRI and echocardiogram prior to the haemodynamic study. The haemdynamic study will be performed in the catheter lab. During that study patients will undergo a temporary pacing procedure with pacing of multiple sites of the heart and multiple haemodynamic recordings. This will be conducted under local anaesthetic and sedation. Total procedure time will be approximately 2 hours.

Diagnostic Test: Acute Haemodynamic Study

Interventions

Acute Haemodynamic Study DIAGNOSTIC_TEST

Multisite temporary pacing

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Guy's and St Thomas' NHS Foundation Trust: lead

Related Publications (5)

• 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.

  PMID: 36723919 BACKGROUND

• 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.

  PMID: 34447992 BACKGROUND

• 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.

  PMID: 36871285 BACKGROUND

• 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.

  PMID: 36575808 BACKGROUND

• 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.

  PMID: 28492288 BACKGROUND

MeSH Terms

Conditions

Heart Failure, Diastolic

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases

Central Study Contacts

Prof Christopher Aldo Rinaldi, MD, MBBS, FRCP, FHRS

CONTACT

0207188 7188; aldo.rinaldi@gstt.nhs.uk

Dr Sandra Howell, MBBS, MSc, MSc

CONTACT

0207188 7188; sandra.howell@kcl.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an observational cohort mechanistic study.

Study Record Dates

• First Submitted: June 5, 2024
• First Posted: June 20, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: June 20, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share