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PacemakerCRTNCT05993585

The Effect of CRT on the Frank Starling Mechanism

A study testing Other: Test Of The Frank Starling Mechanism - Adjustment Of Av Delay And Measurement Of Pre-load -CRT in people with Pacemaker and Heartfailure, run by Guy's and St Thomas' NHS Foundation Trust at 1 site in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pacemaker, Heartfailure
What is being tested?
Other: Test Of The Frank Starling Mechanism - Adjustment Of Av Delay And Measurement Of Pre-load -CRT
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited Kingdom
Study dates
15 Jan 2024to 2 Jun 2025
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • • 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%.

Who cannot join

  • • 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

Trial locations and contacts

1 site in 1 country.

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

44 020 7188 9257

sandra.howell@kcl.ac.uk

United Kingdom1 site, 1 recruiting

  • Guy's and St Thomas' NHS Trust

    London, SE1 7EH

    Sandra N Howell/Dr, Med State Exam, MSc, MSc, 020 7188 9257, sandra.howell@kcl.ac.uk

    Christopher Aldo Rinaldi/Professor, MD, FHRS

    Recruiting

Other trials in United Kingdom

About this study

Official title: 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.

Read more

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.
Read the 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.

Being tested
Test Of The Frank Starling Mechanism - Adjustment Of Av Delay And Measurement Of Pre-load -Control, Other: Test Of The Frank Starling Mechanism - Adjustment Of Av Delay And Measurement Of Pre-load -CRT
Keywords
Frank Starling Mechanism, CRT

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Test Of The Frank Starling Mechanism - Adjustment Of Av Delay And Measurement Of Pre-load -ControlOther

    (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

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

    (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.

Study groups in NCT05993585
Study groupRoleWhat they receive
CRT GroupExperimentalCRT 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.
Receives: Other: Test Of The Frank Starling Mechanism - Adjustment Of Av Delay And Measurement Of Pre-load -Control
Control GroupActive comparatorControl group: patients with an existing dual chamber pacemaker and with preserved ejection fraction
Receives: Other: Other: Test Of The Frank Starling Mechanism - Adjustment Of Av Delay And Measurement Of Pre-load -CRT

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

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

Secondary outcomes (6)

  1. Left ventricular end-systolic volume (ml)

    Difference in left ventricular end-systolic volume in millimetres recorded on echocardiogram

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

  2. Left ventricular ejection fraction (%)

    Difference in Left ventricular ejection fraction in percent measured on echocardiogram

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

  3. Quality of life with heart failure symptoms

    Quality of life in heart failure assessed by Minnesota Living with Heart Failure Questionnaire

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

  4. Heart failure symptoms

    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)

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

  5. Packer's clinical composite score

    Difference in patient outcome measured by the clinical composite score - the score ranges from improved to unchanged or worsened

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

  6. Difference in baseline Starling mechanics between CRT group and control group

    Difference in stroke volume in millilitres during the pacing test (starling mechanism test) between the CRT and control group

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2023
  2. Study start15 Jan 2024
  3. Primary completion2 Jun 2025 (estimated)
  4. Study completion2 Jun 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Single centre trial - observational cohort study
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05993585
Sponsor's protocol ID
318500
Acronym
CRT
Status last verified
Mar 2024
First submitted
31 Jul 2023
Last updated
26 Mar 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Non-identifiable data will be shared upon request

Publications

  • Kim JH, Kang KW, Chin JY, Kim TS, Park JH, Choi YJ. Major determinant of the occurrence of pacing-induced cardiomyopathy in complete atrioventricular block: a multicentre, retrospective analysis over a 15-year period in South Korea. BMJ Open. 2018 Feb 8;8(2):e019048. doi: 10.1136/bmjopen-2017-019048.

    PubMed 29439074

  • Curtis AB, Worley SJ, Adamson PB, Chung ES, Niazi I, Sherfesee L, Shinn T, Sutton MS; Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) Trial Investigators. Biventricular pacing for atrioventricular block and systolic dysfunction. N Engl J Med. 2013 Apr 25;368(17):1585-93. doi: 10.1056/NEJMoa1210356.

    PubMed 23614585

  • Tayal B, Fruelund P, Sogaard P, Riahi S, Polcwiartek C, Atwater BD, Gislason G, Risum N, Torp-Pedersen C, Kober L, Kragholm KH. Incidence of heart failure after pacemaker implantation: a nationwide Danish Registry-based follow-up study. Eur Heart J. 2019 Nov 21;40(44):3641-3648. doi: 10.1093/eurheartj/ehz584.

    PubMed 31504437

  • Chan JY, Fang F, Zhang Q, Fung JW, Razali O, Azlan H, Lam KH, Chan HC, Yu CM. Biventricular pacing is superior to right ventricular pacing in bradycardia patients with preserved systolic function: 2-year results of the PACE trial. Eur Heart J. 2011 Oct;32(20):2533-40. doi: 10.1093/eurheartj/ehr336. Epub 2011 Aug 29.

    PubMed 21875860

  • Kiehl EL, Makki T, Kumar R, Gumber D, Kwon DH, Rickard JW, Kanj M, Wazni OM, Saliba WI, Varma N, Wilkoff BL, Cantillon DJ. Incidence and predictors of right ventricular pacing-induced cardiomyopathy in patients with complete atrioventricular block and preserved left ventricular systolic function. Heart Rhythm. 2016 Dec;13(12):2272-2278. doi: 10.1016/j.hrthm.2016.09.027.

    PubMed 27855853

  • Ebert M, Jander N, Minners J, Blum T, Doering M, Bollmann A, Hindricks G, Arentz T, Kalusche D, Richter S. Long-Term Impact of Right Ventricular Pacing on Left Ventricular Systolic Function in Pacemaker Recipients With Preserved Ejection Fraction: Results From a Large Single-Center Registry. J Am Heart Assoc. 2016 Jul 21;5(7):e003485. doi: 10.1161/JAHA.116.003485.

    PubMed 27444509

  • Kirk JA, Holewinski RJ, Kooij V, Agnetti G, Tunin RS, Witayavanitkul N, de Tombe PP, Gao WD, Van Eyk J, Kass DA. Cardiac resynchronization sensitizes the sarcomere to calcium by reactivating GSK-3beta. J Clin Invest. 2014 Jan;124(1):129-38. doi: 10.1172/JCI69253.

    PubMed 24292707

  • Stachowski-Doll MJ, Papadaki M, Martin TG, Ma W, Gong HM, Shao S, Shen S, Muntu NA, Kumar M, Perez E, Martin JL, Moravec CS, Sadayappan S, Campbell SG, Irving T, Kirk JA. GSK-3beta Localizes to the Cardiac Z-Disc to Maintain Length Dependent Activation. Circ Res. 2022 Mar 18;130(6):871-886. doi: 10.1161/CIRCRESAHA.121.319491. Epub 2022 Feb 16.

    PubMed 35168370

  • Niederer SA, Plank G, Chinchapatnam P, Ginks M, Lamata P, Rhode KS, Rinaldi CA, Razavi R, Smith NP. Length-dependent tension in the failing heart and the efficacy of cardiac resynchronization therapy. Cardiovasc Res. 2011 Feb 1;89(2):336-43. doi: 10.1093/cvr/cvq318. Epub 2010 Oct 14.

    PubMed 20952413

  • Bastarrika G, Brabham WW, O'Brien TX, Costello P, Schoepf UJ. Dual-source computed tomography assessment of malfunctioning mechanical prosthetic valve. Ann Thorac Surg. 2009 May;87(5):e50. doi: 10.1016/j.athoracsur.2009.02.044. No abstract available.

    PubMed 19379857

  • Jansen AH, Bracke FA, van Dantzig JM, Meijer A, van der Voort PH, Aarnoudse W, van Gelder BM, Peels KH. Correlation of echo-Doppler optimization of atrioventricular delay in cardiac resynchronization therapy with invasive hemodynamics in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2006 Feb 15;97(4):552-7. doi: 10.1016/j.amjcard.2005.08.076. Epub 2006 Jan 4.

    PubMed 16461055

  • Shinbane JS, Chu E, DeMarco T, Sobol Y, Fitzpatrick AP, Lau DM, Klinski C, Schiller NB, Griffin JC, Chatterjee K. Evaluation of acute dual-chamber pacing with a range of atrioventricular delays on cardiac performance in refractory heart failure. J Am Coll Cardiol. 1997 Nov 1;30(5):1295-300. doi: 10.1016/s0735-1097(97)00307-0.

    PubMed 9350930

  • Hochleitner M, Hortnagl H, Hortnagl H, Fridrich L, Gschnitzer F. Long-term efficacy of physiologic dual-chamber pacing in the treatment of end-stage idiopathic dilated cardiomyopathy. Am J Cardiol. 1992 Nov 15;70(15):1320-5. doi: 10.1016/0002-9149(92)90769-u.

    PubMed 1442585

  • Guardigli G, Ansani L, Percoco GF, Toselli T, Spisani P, Braggion G, Antonioli GE. AV delay optimization and management of DDD paced patients with dilated cardiomyopathy. Pacing Clin Electrophysiol. 1994 Nov;17(11 Pt 2):1984-8. doi: 10.1111/j.1540-8159.1994.tb03785.x.

    PubMed 7845803

  • Auricchio A, Salo RW. Acute hemodynamic improvement by pacing in patients with severe congestive heart failure. Pacing Clin Electrophysiol. 1997 Feb;20(2 Pt 1):313-24. doi: 10.1111/j.1540-8159.1997.tb06176.x.

    PubMed 9058869

Questions about this trial

What is this clinical trial studying?

A study testing Other: Test Of The Frank Starling Mechanism - Adjustment Of Av Delay And Measurement Of Pre-load -CRT in people with Pacemaker and Heartfailure, run by Guy's and St Thomas' NHS Foundation Trust at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 26 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Sandra N Howell/Dr, Med State Exam, MSc, MSc (44 020 7188 9257, sandra.howell@kcl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Difference in starling mechanism (time frame: Prior to pacing test (starling mechanism test) and after six months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05993585, which also lists 29 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2024.

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