The Effect of CRT on the Frank Starling Mechanism

NCT05993585 | Recruiting DMC

• 1 other identifier: 318500
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators are examining a scientific principle called the Frank Starling Mechanism and how it relates to Cardiac Resynchronisation Therapy (CRT), a form of pacemaker therapy used in the treatment of heart failure. The Frank Starling Mechanism is an established biological principle. The law states that the stroke volume of the heart increases in response to an increase in the volume of blood in the ventricles, before contraction, when all other factors remain constant. In other words, the law states that the more blood enters the heart, the more blood is pumped out of the heart with any given beat. There is some evidence that in some patients with chronic heart conditions, the Frank Starling Mechanism is LESS EFFECTIVE, meaning that the heart is less able to cope with a reduction in heart pumping function over time. There is also evidence that treatment with CRT may IMPROVE the Frank Starling Mechanism - evidence for this has been shown in dog and mice hearts, however, has never been shown in humans. The investigators aim to conduct a study where subjects undergo an ultrasound scan of the heart (echocardiogram) whilst the participants pacemaker settings are temporarily changed. This allows the investigators to measure the pumping function of the heart as more blood enters the heart. The investigators will perform this test on 20 participants before and after CRT, as well as 20 participants who have pacemakers, but no heart failure. This study aims to test 3 hypotheses.

1. 1.In participants with pacemakers, a REDUCED Frank Starling Mechanism predicts which participants go on to develop heart failure.
2. 2.Treatment with CRT IMPROVES the Frank Starling Mechanism in participants with pacemakers and heart failure.
3. 3.The degree of improvement of the Frank Starling Mechanism after treatment with CRT predicts which participants will respond to this treatment.

Conditions

Pacemaker; Heartfailure

Keywords

Frank Starling Mechanism; CRT

Outcome Measures

Primary Outcomes (1)

• Difference in starling mechanism

  1\. Difference in maximum change in stroke volume (SV) in millilitres with AV delay modification "Starling mechanics" pre-CRT versus post-CRT (difference between lowest and highest SV).

  Prior to pacing test (starling mechanism test) and after six months

Secondary Outcomes (6)

• Left ventricular end-systolic volume (ml)

  Prior to pacing test (starling mechanism test) and after six months

• Left ventricular ejection fraction (%)

  Prior to pacing test (starling mechanism test) and after six months

• Quality of life with heart failure symptoms

  Prior to pacing test (starling mechanism test) and after six months

• Heart failure symptoms

  Prior to pacing test (starling mechanism test) and after six months

• Packer's clinical composite score

  Prior to pacing test (starling mechanism test) and at six months

Study Arms (2)

CRT Group

EXPERIMENTAL

CRT group: We will include patients with symptomatic heart failure (LV ejection fraction \<35% on TTE, NYHA II-IV) and an RV pacing percentage of \>40%, thus meeting ESC Criteria for CRT upgrade.

Other: Test Of The Frank Starling Mechanism - Adjustment Of Av Delay And Measurement Of Pre-load -Control

Control Group

ACTIVE COMPARATOR

Control group: patients with an existing dual chamber pacemaker and with preserved ejection fraction

Other: Other: Test Of The Frank Starling Mechanism - Adjustment Of Av Delay And Measurement Of Pre-load -CRT

Interventions

Test Of The Frank Starling Mechanism - Adjustment Of Av Delay And Measurement Of Pre-load -Control OTHER

(Control Group): One test of the Starling mechanism Visit 1: Sign consent form, doctor assessment, electrocardiogram (ECG), Starling Test. If patients are in this category, this will be their only research visit

CRT Group

Other: Test Of The Frank Starling Mechanism - Adjustment Of Av Delay And Measurement Of Pre-load -CRT OTHER

(CRT Group): Two tests of the Starling mechanisms Visit 1: Sign consent form, assessment by doctor, electrocardiogram (ECG), Test of the Starling mechanism Visit 2: CRT upgrade procedure - your Cardiologist will explain this procedure to you. Visit 3: CRT pacing check at 6 weeks post-procedure Visit 4: Assessment by doctor, ECG, Echocardiogram, Test of the Starling mechanism at 6 months post-procedure.

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent to participate and willing to comply with the clinical investigation plan and follow-up schedule.
• Existing dual chamber pacemaker or ICD including atrial lead and RV lead.
• RV pacing percentage \>40%.
• CRT group - Severe left ventricular systolic impairment (LVEF≤35%). Clinical symptoms of heart failure despite optimum medical therapy (NYHA class II-IV).
• Control group - LVEF \>50%.

You may not qualify if:

• Previous treated with CRT (existing LV lead/His-Bundle lead/Left Bundle Branch Area lead).
• Persistent atrial fibrillation
• Female participants who are pregnant, lactating or planning pregnancy during the course of the study.
• Participation in other studies with active treatment / investigational arm

Sponsors & Collaborators

• Guy's and St Thomas' NHS Foundation Trust: lead
• King's College London: collaborator

Study Sites (1)

Guy's and St Thomas' NHS Trust

London, SE1 7EH, United Kingdom

RECRUITING

Related Publications (29)

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Study Officials

• Christopher Aldo Rinaldi/Professor, MD, FHRS

  Guy's and St Thomas' NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Steven Niederer/Professor, PhD

  King's College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sandra N Howell/Dr, Med State Exam, MSc, MSc

CONTACT

44 020 7188 9257; sandra.howell@kcl.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single centre trial - observational cohort study

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: August 15, 2023
• Study Start: January 15, 2024
• Primary Completion: June 2, 2025
• Study Completion: June 2, 2025
• Last Updated: March 26, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Non-identifiable data will only be available after the end of the study
• Access Criteria: Fully anonymised data available upon request via email

Locations

GB (1)