The Effect of CRT on the Frank Starling Mechanism (CRT)

March 25, 2024 updated by: Guy's and St Thomas' NHS Foundation Trust

The Effects of Cardiac Resynchronisation Therapy on the Frank Starling Mechanism in Patients With Heart Failure

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The primary research investigation in this study is a non-invasive test of the Frank Starling mechanism, which involves performing a transthoracic echocardiogram (ultrasound scan of the heart) whilst temporarily changing pacemaker settings to mimic conditions such as faster heart rates or increased blood flow to the heart. Measurements taken from the echocardiogram during these changes in pacemaker settings will be used to determine the effectiveness of the heart's Starling Mechanism. This test will last between 20-40 minutes. No special preparation is needed and participants will be able to go home immediately afterwards. Pacemaker settings will be returned to normal once the test is completed.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
      • London, United Kingdom, SE1 7EH
        • Recruiting
        • Guy's and St Thomas' NHS Trust
        • Contact:
        • Principal Investigator:
          • Christopher Aldo Rinaldi/Professor, MD, FHRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • • 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%.

Exclusion Criteria:

  • • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CRT Group
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): 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
Active Comparator: Control Group
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
(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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in starling mechanism
Time Frame: Prior to pacing test (starling mechanism test) and after six months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left ventricular end-systolic volume (ml)
Time Frame: Prior to pacing test (starling mechanism test) and after six months
Difference in left ventricular end-systolic volume in millimetres recorded on echocardiogram
Prior to pacing test (starling mechanism test) and after six months
Left ventricular ejection fraction (%)
Time Frame: Prior to pacing test (starling mechanism test) and after six months
Difference in Left ventricular ejection fraction in percent measured on echocardiogram
Prior to pacing test (starling mechanism test) and after six months
Quality of life with heart failure symptoms
Time Frame: Prior to pacing test (starling mechanism test) and after six months
Quality of life in heart failure assessed by Minnesota Living with Heart Failure Questionnaire
Prior to pacing test (starling mechanism test) and after six months
Heart failure symptoms
Time Frame: Prior to pacing test (starling mechanism test) and after six months
New York Heart Association ( NYHA) class - breathlessness on different levels of exercise - from walking on the flat (NYHA 2) up to limited by breathlessness on little movement (NYHA 4)
Prior to pacing test (starling mechanism test) and after six months
Packer's clinical composite score
Time Frame: Prior to pacing test (starling mechanism test) and at six months
Difference in patient outcome measured by the clinical composite score - the score ranges from improved to unchanged or worsened
Prior to pacing test (starling mechanism test) and at six months
Difference in baseline Starling mechanics between CRT group and control group
Time Frame: Prior to pacing test (starling mechanism test) and at six months
Difference in stroke volume in millilitres during the pacing test (starling mechanism test) between the CRT and control group
Prior to pacing test (starling mechanism test) and at six months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guy's and St Thomas' NHS Foundation Trust

Collaborators

King's College London

Investigators

  • Principal Investigator: Christopher Aldo Rinaldi/Professor, MD, FHRS, Guy's and St Thomas' NHS Trust
  • Principal Investigator: Steven Niederer/Professor, PhD, King's College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 15, 2024

Primary Completion (Estimated)

June 2, 2025

Study Completion (Estimated)

June 2, 2025

Study Registration Dates

First Submitted

July 31, 2023

First Submitted That Met QC Criteria

August 8, 2023

First Posted (Actual)

August 15, 2023

Study Record Updates

Last Update Posted (Actual)

March 26, 2024

Last Update Submitted That Met QC Criteria

March 25, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 318500

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Non-identifiable data will be shared upon request

IPD Sharing Time Frame

Non-identifiable data will only be available after the end of the study

IPD Sharing Access Criteria

Fully anonymised data available upon request via email

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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