Heart Failure, SystolicQUARTRMASTERNCT02997670
Quartet Lead With Defibrillator Multisite Algorithmic Cardiac Resynchronisation Therapy Optimisation
A study testing Algorithmic Cardiac Resynchronisation Therapy Optimisation in people with Heart Failure, Systolic, run by Cardiff and Vale University Health Board at 1 site in United Kingdom.
Trial summary
Cardiac resynchronisation therapy (CRT) improves outcomes and symptoms in selected patients with heart failure. However, around one third of suitable patients do not demonstrate benefit following device implantation when assessed by echocardiography (heart scanning). This group has poorer outcomes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Systolic
- What is being tested?
- Algorithmic Cardiac Resynchronisation Therapy Optimisation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jul 2019to 1 Jul 2019
- 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
- Successful implantation of CRT-D device with quadripolar left ventricular lead and dual coil right ventricular lead.
Who cannot join
- failed device implantation
- inability to complete the follow-up process
- inability to provide full written consent. Patients unable to perform cardiopulmonary exercise testing will be excluded from this assessment only and will be able to complete the remaining assessments.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospital of Wales
Cardiff, Wales, CF14 4XW
About this study
Cardiac resynchronisation therapy (CRT) improves outcomes and symptoms in selected patients with heart failure. However, around one third of suitable patients do not demonstrate benefit following device implantation when assessed by echocardiography (heart scanning). This group has poorer outcomes.
Response rate can be enhanced by altering timing delays between the pacing leads, but some patients still fail to improve.
Read more
Quadripolar left ventricular leads are now widely used in CRT. The lead's four poles increase the number of conformations available to the programmer, allowing multiple vectors to be programmed simultaneously or sequentially. This allows programming to avoid, for example, a patch of scar and find an area that will respond better to pacing. This technique is known as multi-site pacing. CRT is often implanted along with a defibrillator lead in the right ventricle, known as CRT-D. The defibrillator lead offers further combinations for pacing.
Goal of Research To evaluate an algorithm for assessing different multi-site pacing combinations in optimisation of CRT
Outline The investigators will recruit 24 consecutive patients undergoing CRT-D implantation for conventional indications at our hospital. At baseline, patients will undergo echocardiography, exercise testing and assessments of functional ability and quality of life. The device will be implanted as standard. Optimisation will be performed with an algorithm using different vector combinations and assessing the heart's efficiency through echocardiography and invasive pressure monitoring. The pacemaker will be programmed with standard settings. After twelve weeks, the baseline investigations and optimisation algorithm will be repeated and the device programmed according to the maximum efficiency. After a further 12 weeks, the same parameters will be measured to look for improved response to CRT.
Potential Benefit To increase the response rate to cardiac resynchronisation therapy and improve reliability of the technique
Read the detailed description
Study Design: This is an open-label, single centre, prospective, cohort study to assess the effect of algorithmic, echocardiography-guided optimisation of CRT-D following implantation of a left ventricular quadripolar lead.
Introduction and background:
There is now considerable evidence that cardiac resynchronisation therapy (CRT) improves outcomes and symptoms in patients with heart failure. However, around a third of patients do not demonstrate any haemodynamic or functional benefit following device implantation. Earlier studies have used a cut-off of 15% reduction in left ventricular end-systolic volume to define response to CRT.
Failure to respond to CRT is felt to be multifactorial. Issues include:
- Anatomical limitations in terms of lead placement (the lead must be placed within a branch of the coronary sinus vein and therefore targeting to the site of maximum contraction delay can be difficult)
- Presence of areas of scar tissue, which are resistant to being paced
- Phrenic nerve stimulation with some pacing sites. The phrenic nerve runs close to the heart and may be stimulated by the pacemaker, with the effect that the patient's diaphragm is stimulated and they experience persistent hiccups.
- High pacing thresholds, which means that increased power from the pacemaker must be used to create a successful pacing stimulus (capture) and that in some instances, capture may not be achieved. This can be due to scar or to poor contact with the heart tissue.
Previous work has demonstrated that response can be improved in some patients by optimisation of inter- and intra-ventricular dyssynchrony and atrio-ventricular delay. However, this optimisation is limited by the fixed location of the leads after implantation, with pacing possible from the lead tip only. Multi-site pacing (MSP) with a quadripolar left ventricular lead has been introduced to increase the number of conformations available to the programmer and is especially useful in reducing phrenic nerve capture. Additionally, multiple vectors can be programmed sequentially or simultaneously, allowing for incorporation of a greater number of myocardial segments. Quadripolar left ventricular leads are now being routinely used in many hospitals. They offer new opportunities for optimising CRT-D (resynchronisation-defibrillator) devices by altering the pacing vectors between the four different poles on the lead and the two defibrillator coils to give hundreds of possible pacing combinations.
Several recent studies have been published looking at the effect of multi-site pacing on effectiveness of CRT therapy. Generally these employ limited vector combinations, but have already demonstrated beneficial effects on haemodynamics and echocardiographic measures of heart function. The evaluation of an algorithm that examines many more vector combinations, including in combination with the right ventricular defibrillator coils, has not been performed. The researchers propose to investigate this method of optimisation.
A gold standard for optimisation of CRT has yet to be defined. Methods employed predominantly include invasive haemodynamic measurement and echocardiography. The ideal method would have low inter-observer variability, high ease of use and rapid sampling rate to allow adjustments to be made and evaluated quickly. USCOM, a continuous-wave Doppler method of continually assessing cardiac output, has been successfully used in optimisation of CRT and has gained a patent, however has so far been used to optimise atrio-ventricular delay only. This method may prove a more accurate, rapid and convenient way to rapidly assess response to changes in pacemaker parameters. The investigators plan to evaluate these three methods of assessment and correlate with each other and with cardiovascular outcomes.
Hypothesis:
Use of an algorithm in optimisation of cardiac resynchronisation therapy systems containing quadripolar left ventricular leads and dual coil right ventricular leads will increase response rate to this therapy.
Study structure:
Patients will be recruited consecutively amongst those undergoing implantation of a CRT-D device. At baseline, they will undergo assessment of functional capacity and echocardiographic parameters as well as invasive left ventricular pressure monitoring. The device will be implanted under normal laboratory conditions, aiming for a postero-lateral or lateral cardiac vein left ventricular lead position. Algorithmic echocardiography-guided optimisation of the devices will be conducted at the time of device implantation. Further assessment will be conducted simultaneously with haemodynamic left ventricular pressure monitoring and Ultrasound Cardiac Output Monitoring (USCOM) during device optimisation. The devices will then be programmed with standard CRT parameters. Subjects will be seen at 12 weeks for echocardiographic and functional assessment, following which algorithmic optimisation will be repeated with haemodynamic and echocardiographic monitoring concurrently. Further assessment will be performed at 24 weeks as per baseline, following which the study will end.
Study population: 24 men and women, 18 years and older, who are able to attend follow-up assessment 12 and 24 weeks after implantation.
- Conditions
- Heart Failure, Systolic
- Being tested
- Algorithmic Cardiac Resynchronisation Therapy Optimisation
- Keywords
- Cardiac resynchronization pacing therapy
- Medical subject headings
- Heart Failure, Systolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Algorithmic Cardiac Resynchronisation Therapy OptimisationOther
Use of a computer algorithm to run through multiple combinations of pacing options in patients who have a Cardiac resynchronisation pacemaker with defibrillator where a quadripolar lead has been implanted. These quadripolar leads offer extra options for pacing locations across the heart, as well as for different combinations and sequences of pacing stimuli.
| Study group | Role | What they receive |
|---|---|---|
| Main patient cohort | Experimental | Algorithmic Cardiac Resynchronisation Therapy Optimisation; Patients requiring CRT-D enrolled to receive algorithmic CRT optimisation at their device implantation. They will then be programmed to standard CRT settings for 12 weeks. Assessments will be performed and they will again undergo CRT optimisation using the specified algorithm. This time, they will be programmed to the settings giving maximal cardiac output on echocardiography, as assessed by LVOT VTI. After a further 12 weeks, they will again undergo assessment and the study will terminate. Receives: Other: Algorithmic Cardiac Resynchronisation Therapy Optimisation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in left ventricular end-systolic volume in patients undergoing algorithmic optimisation of CRT-D compared with usual device settings
End-systolic volume will be measured on echocardiography using Simpson's method. Where image quality precludes a full biplane assessment, single plane will be used with the apical 4-chamber view, or alternatively left ventricular end-systolic diameter will be used to calculate volume using the Teicholz method.
Measured: 24 weeks
Secondary outcomes (16)
Feasibility of algorithmic, echocardiography-guided CRT-D optimisation with quadripolar left ventricular leads in clinical practice
To see whether our optimisation algorithm is acceptable to patients and easy to perform in clinical practice.
Measured: 24 weeks
Correlation between invasive haemodynamic studies with non-invasive ultrasound-based methods in optimising CRT-D
Attempt to establish a gold standard for optimisation of CRT devices by comparing invasive haemodynamic monitoring, echocardiographic parameters and cardiac output by ultrasound cardiac output monitoring (USCOM)
Measured: 24 weeks
Change in left ventricular end diastolic pressure with algorithmic optimisation of CRT-D compared with usual device settings
A measurement of left ventricular end-diastolic pressure will be made via invasive left ventricular monitoring after programming with usual settings and again after programming using algorithmic optimisation of the CRT-D device.
Measured: 24 weeks
Feasibility of ultrasound cardiac output monitoring (USCOM) in optimisation of CRT devices in clinical practice
Use of USCOM has been documented in optimisation of CRT, but not in such rapidly-changing algorithmic optimisation. We plan to assess whether it is feasible to use this in clinical practice as a replacement for a full echocardiogram.
Measured: At baseline and at 12 weeks
Change in peak oxygen consumption with algorithmic CRT-D optimisation compared with usual device settings
Assessment of peak oxygen consumption as measured by cardiopulmonary exercise testing after usual settings compared with settings after algorithmic optimisation.
Measured: 24 weeks
Change in left ventricular ejection fraction with algorithmic CRT-D optimisation compared with usual device settings.
Ejection fraction will be measured on echocardiography by Simpson's biplane method of discs. Where image quality precludes a full biplane assessment, single plane will be used with the apical 4-chamber view. Participants whose views are not sufficiently good quality for either of these measurements will be excluded from this outcome measure.
Measured: 24 weeks
Change in left ventricular end-diastolic volume with algorithmic CRT-D optimisation compared with usual device settings.
End-diastolic volume will be measured on echocardiography using Simpson's method. Where image quality precludes a full biplane assessment, single plane will be used with the apical 4-chamber view, or the Teicholz method will be used to estimate end-diastolic volume by measuring left ventricular end-diastolic diameter.
Measured: 24 weeks
Change in left ventricular diastolic filling time with algorithmic CRT-D optimisation compared with usual device settings.
Diastolic filling time will be measured on echocardiography using pulsed wave Doppler over the mitral inflow of the left ventricle.
Measured: 24 weeks
Change in left ventricular outflow tract velocity time integral (LVOT VTI) with algorithmic CRT-D optimisation compared with usual device settings.
LVOT VTI will be measured on echocardiography using pulsed wave Doppler within the left ventricular outflow tract, within 1cm of the aortic valve where a clear envelope is visible.
Measured: 24 weeks
Change in longitudinal and global longitudinal strain (GLS) with algorithmic CRT-D optimisation compared with usual device settings.
Longitudinal strain of the left ventricle will be measured on echocardiography using speckle tracking software
Measured: 24 weeks
Change in radial strain with algorithmic CRT-D optimisation compared with usual device settings.
Radial strain of the left ventricle will be measured on echocardiography using speckle tracking software
Measured: 24 weeks
Change in distance walked on a 6-minute hall walk test with algorithmic CRT-D optimisation compared with usual device settings
Patients will undergo a hall walk test at baseline, 12 weeks (with usual settings) and 24 weeks (following algorithmic optimisation) and the difference in distance walked will be analysed.
Measured: 24 weeks
Change in New York Heart Association functional class with algorithmic CRT-D optimisation compared with usual device settings.
Functional status will be assessed at baseline, after 12 weeks (with usual settings) and after 24 weeks (with optimised settings) and the change in class will be recorded.
Measured: 24 weeks
Change in score in the Minnesota Living with Heart Failure Questionnaire (MLHFQ) between algorithmically optimised CRT-D and usual device settings.
Patients will complete a questionnaire at baseline, 12 weeks (with usual settings) and 24 weeks (following algorithmic optimisation) and the difference in scores will be analysed. The Minnesota Living with Heart Failure Questionnaire is a validated and commonly used tool for assessing symptoms and activities of daily living in heart failure patients.
Measured: 24 weeks
Change in cardiac output measured by the novel technique of Ultra-Sound Cardiac Output Monitoring (USCOM) with algorithmic CRT-D optimisation compared with usual device settings
USCOM is a validated technique that correlates well with echocardiographic and Doppler measurements of cardiac output and is performed using a simple probe placed at several points over the chest wall.
Measured: 24 weeks
Number of patients suffering adverse events during the study period
Hospital patient record systems and telephone calls will be used to find out about hospital admissions and mortality during the study period. An adverse event will be defined as an admission to hospital or death from any cause.
Measured: From patient enrollment through study completion, an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2016 (estimated)
- Study start1 Jul 2019
- Primary completion1 Jul 2019
- Study completion1 Jul 2019
Why it stopped: Work focused in other areas, other groups working on this.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Heart Failure, SystolicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cardiff and Vale University Health Board
- Sponsor type
- Other government
- Collaborators
- Abbott Medical Devices
- Responsible party
- Principal investigator, Freya Lodge, Cardiff and Vale University Health Board
- Investigators
- Freya M Lodge, MBBS, Principal investigator, Cardiff and Vale University Health BoardZaheer R Yousef, MBBS, Study director, Cardiff and Vale University Health Board
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02997670
- Sponsor's protocol ID
- 16/WA/0370 186610
- Acronym
- QUARTRMASTER
- Status last verified
- Jan 2020
- First submitted
- 7 Dec 2016
- Last updated
- 22 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data available on individual written request at the discretion of the investigators.
Publications
Auricchio A, Stellbrink C, Sack S, Block M, Vogt J, Bakker P, Huth C, Schondube F, Wolfhard U, Bocker D, Krahnefeld O, Kirkels H; Pacing Therapies in Congestive Heart Failure (PATH-CHF) Study Group. Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Cardiol. 2002 Jun 19;39(12):2026-33. doi: 10.1016/s0735-1097(02)01895-8.
PubMed 12084604Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, Ellestad M, Trupp RJ, Underwood J, Pickering F, Truex C, McAtee P, Messenger J; MIRACLE Study Group. Multicenter InSync Randomized Clinical Evaluation. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002 Jun 13;346(24):1845-53. doi: 10.1056/NEJMoa013168.
PubMed 12063368Young JB, Abraham WT, Smith AL, Leon AR, Lieberman R, Wilkoff B, Canby RC, Schroeder JS, Liem LB, Hall S, Wheelan K; Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial. JAMA. 2003 May 28;289(20):2685-94. doi: 10.1001/jama.289.20.2685.
PubMed 12771115Daubert C, Gold MR, Abraham WT, Ghio S, Hassager C, Goode G, Szili-Torok T, Linde C; REVERSE Study Group. Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. J Am Coll Cardiol. 2009 Nov 10;54(20):1837-46. doi: 10.1016/j.jacc.2009.08.011. Epub 2009 Oct 1.
PubMed 19800193Linde C, Abraham WT, Gold MR, St John Sutton M, Ghio S, Daubert C; REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) Study Group. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol. 2008 Dec 2;52(23):1834-1843. doi: 10.1016/j.jacc.2008.08.027. Epub 2008 Nov 7.
PubMed 19038680Chung ES, Katra RP, Ghio S, Bax J, Gerritse B, Hilpisch K, Peterson BJ, Feldman DS, Abraham WT. Cardiac resynchronization therapy may benefit patients with left ventricular ejection fraction >35%: a PROSPECT trial substudy. Eur J Heart Fail. 2010 Jun;12(6):581-7. doi: 10.1093/eurjhf/hfq009. Epub 2010 Feb 11.
PubMed 20150328Osca J, Alonso P, Cano O, Andres A, Miro V, Tello MJ, Olague J, Martinez L, Salvador A. The use of multisite left ventricular pacing via quadripolar lead improves acute haemodynamics and mechanical dyssynchrony assessed by radial strain speckle tracking: initial results. Europace. 2016 Apr;18(4):560-7. doi: 10.1093/europace/euv211. Epub 2015 Sep 1.
PubMed 26333378Rinaldi CA, Burri H, Thibault B, Curnis A, Rao A, Gras D, Sperzel J, Singh JP, Biffi M, Bordachar P, Leclercq C. A review of multisite pacing to achieve cardiac resynchronization therapy. Europace. 2015 Jan;17(1):7-17. doi: 10.1093/europace/euu197. Epub 2014 Sep 11.
PubMed 25214507Pappone C, Calovic Z, Vicedomini G, Cuko A, McSpadden LC, Ryu K, Romano E, Saviano M, Baldi M, Pappone A, Ciaccio C, Giannelli L, Ionescu B, Petretta A, Vitale R, Fundaliotis A, Tavazzi L, Santinelli V. Multipoint left ventricular pacing improves acute hemodynamic response assessed with pressure-volume loops in cardiac resynchronization therapy patients. Heart Rhythm. 2014 Mar;11(3):394-401. doi: 10.1016/j.hrthm.2013.11.023. Epub 2013 Nov 28.
PubMed 24291411Siu CW, Tse HF, Lee K, Chan HW, Chen WH, Yung C, Lee S, Lau CP. Cardiac resynchronization therapy optimization by ultrasonic cardiac output monitoring (USCOM) device. Pacing Clin Electrophysiol. 2007 Jan;30(1):50-5. doi: 10.1111/j.1540-8159.2007.00579.x.
PubMed 17241315Zanon F, Baracca E, Pastore G, Marcantoni L, Fraccaro C, Lanza D, Picariello C, Aggio S, Roncon L, Dell'Avvocata F, Rigatelli G, Pacetta D, Noventa F, Prinzen FW. Multipoint pacing by a left ventricular quadripolar lead improves the acute hemodynamic response to CRT compared with conventional biventricular pacing at any site. Heart Rhythm. 2015 May;12(5):975-81. doi: 10.1016/j.hrthm.2015.01.034. Epub 2015 Jan 24.
PubMed 25625721
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quartet Lead With Defibrillator Multisite Algorithmic Cardiac Resynchronisation Therapy Optimisation
- ClinicalTrials.gov ID
- NCT02997670
- Acronym / sponsor ID
- QUARTRMASTER / 16/WA/0370 186610
- Conditions
- Heart Failure, Systolic
- Keywords
- Cardiac resynchronization pacing therapy
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Work focused in other areas, other groups working on this.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Cardiff and Vale University Health BoardOther government
- Collaborators
- Abbott Medical Devices
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 1 Jul 2019 (actual)
- Study completion
- 1 Jul 2019 (actual)
- First posted
- 20 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cardiac resynchronisation therapy (CRT) improves outcomes and symptoms in selected patients with heart failure. However, around one third of suitable patients do not demonstrate benefit following device implantation when assessed by echocardiography (heart scanning). This group has poorer outcomes.
Response rate can be enhanced by altering timing delays between the pacing leads, but some patients still fail to improve.
Quadripolar left ventricular leads are now widely used in CRT. The lead's four poles increase the number of conformations available to the programmer, allowing multiple vectors to be programmed simultaneously or sequentially. This allows programming to avoid, for example, a patch of scar and find an area that will respond better to pacing. This technique is known as multi-site pacing. CRT is often implanted along with a defibrillator lead in the right ventricle, known as CRT-D. The defibrillator lead offers further combinations for pacing.
Goal of Research To evaluate an algorithm for assessing different multi-site pacing combinations in optimisation of CRT
Outline The investigators will recruit 24 consecutive patients undergoing CRT-D implantation for conventional indications at our hospital. At baseline, patients will undergo echocardiography, exercise testing and assessments of functional ability and quality of life. The device will be implanted as standard. Optimisation will be performed with an algorithm using different vector combinations and assessing the heart's efficiency through echocardiography and invasive pressure monitoring. The pacemaker will be programmed with standard settings. After twelve weeks, the baseline investigations and optimisation algorithm will be repeated and the device programmed according to the maximum efficiency. After a further 12 weeks, the same parameters will be measured to look for improved response to CRT.
Potential Benefit To increase the response rate to cardiac resynchronisation therapy and improve reliability of the technique
Detailed description
Study Design: This is an open-label, single centre, prospective, cohort study to assess the effect of algorithmic, echocardiography-guided optimisation of CRT-D following implantation of a left ventricular quadripolar lead.
Introduction and background:
There is now considerable evidence that cardiac resynchronisation therapy (CRT) improves outcomes and symptoms in patients with heart failure. However, around a third of patients do not demonstrate any haemodynamic or functional benefit following device implantation. Earlier studies have used a cut-off of 15% reduction in left ventricular end-systolic volume to define response to CRT.
Failure to respond to CRT is felt to be multifactorial. Issues include:
- Anatomical limitations in terms of lead placement (the lead must be placed within a branch of the coronary sinus vein and therefore targeting to the site of maximum contraction delay can be difficult)
- Presence of areas of scar tissue, which are resistant to being paced
- Phrenic nerve stimulation with some pacing sites. The phrenic nerve runs close to the heart and may be stimulated by the pacemaker, with the effect that the patient's diaphragm is stimulated and they experience persistent hiccups.
- High pacing thresholds, which means that increased power from the pacemaker must be used to create a successful pacing stimulus (capture) and that in some instances, capture may not be achieved. This can be due to scar or to poor contact with the heart tissue.
Previous work has demonstrated that response can be improved in some patients by optimisation of inter- and intra-ventricular dyssynchrony and atrio-ventricular delay. However, this optimisation is limited by the fixed location of the leads after implantation, with pacing possible from the lead tip only. Multi-site pacing (MSP) with a quadripolar left ventricular lead has been introduced to increase the number of conformations available to the programmer and is especially useful in reducing phrenic nerve capture. Additionally, multiple vectors can be programmed sequentially or simultaneously, allowing for incorporation of a greater number of myocardial segments. Quadripolar left ventricular leads are now being routinely used in many hospitals. They offer new opportunities for optimising CRT-D (resynchronisation-defibrillator) devices by altering the pacing vectors between the four different poles on the lead and the two defibrillator coils to give hundreds of possible pacing combinations.
Several recent studies have been published looking at the effect of multi-site pacing on effectiveness of CRT therapy. Generally these employ limited vector combinations, but have already demonstrated beneficial effects on haemodynamics and echocardiographic measures of heart function. The evaluation of an algorithm that examines many more vector combinations, including in combination with the right ventricular defibrillator coils, has not been performed. The researchers propose to investigate this method of optimisation.
A gold standard for optimisation of CRT has yet to be defined. Methods employed predominantly include invasive haemodynamic measurement and echocardiography. The ideal method would have low inter-observer variability, high ease of use and rapid sampling rate to allow adjustments to be made and evaluated quickly. USCOM, a continuous-wave Doppler method of continually assessing cardiac output, has been successfully used in optimisation of CRT and has gained a patent, however has so far been used to optimise atrio-ventricular delay only. This method may prove a more accurate, rapid and convenient way to rapidly assess response to changes in pacemaker parameters. The investigators plan to evaluate these three methods of assessment and correlate with each other and with cardiovascular outcomes.
Hypothesis:
Use of an algorithm in optimisation of cardiac resynchronisation therapy systems containing quadripolar left ventricular leads and dual coil right ventricular leads will increase response rate to this therapy.
Study structure:
Patients will be recruited consecutively amongst those undergoing implantation of a CRT-D device. At baseline, they will undergo assessment of functional capacity and echocardiographic parameters as well as invasive left ventricular pressure monitoring. The device will be implanted under normal laboratory conditions, aiming for a postero-lateral or lateral cardiac vein left ventricular lead position. Algorithmic echocardiography-guided optimisation of the devices will be conducted at the time of device implantation. Further assessment will be conducted simultaneously with haemodynamic left ventricular pressure monitoring and Ultrasound Cardiac Output Monitoring (USCOM) during device optimisation. The devices will then be programmed with standard CRT parameters. Subjects will be seen at 12 weeks for echocardiographic and functional assessment, following which algorithmic optimisation will be repeated with haemodynamic and echocardiographic monitoring concurrently. Further assessment will be performed at 24 weeks as per baseline, following which the study will end.
Study population: 24 men and women, 18 years and older, who are able to attend follow-up assessment 12 and 24 weeks after implantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Main patient cohort | Experimental | Other: Algorithmic Cardiac Resynchronisation Therapy OptimisationAlgorithmic Cardiac Resynchronisation Therapy Optimisation; Patients requiring CRT-D enrolled to receive algorithmic CRT optimisation at their device implantation. They will then be programmed to standard CRT settings for 12 weeks. Assessments will be performed and they will again undergo CRT optimisation using the specified algorithm. This time, they will be programmed to the settings giving maximal cardiac output on echocardiography, as assessed by LVOT VTI. After a further 12 weeks, they will again undergo assessment and the study will terminate. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Successful implantation of CRT-D device with quadripolar left ventricular lead and dual coil right ventricular lead.
Key exclusion criteria (3 listed)
- failed device implantation
- inability to complete the follow-up process
- inability to provide full written consent. Patients unable to perform cardiopulmonary exercise testing will be excluded from this assessment only and will be able to complete the remaining assessments.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Algorithmic Cardiac Resynchronisation Therapy OptimisationUse of a computer algorithm to run through multiple combinations of pacing options in patients who have a Cardiac resynchronisation pacemaker with defibrillator where a quadripolar lead has been implanted. These quadripolar leads offer extra options for pacing locations across the heart, as well as for different combinations and sequences of pacing stimuli. | Other | Main patient cohort |
Primary outcome
Change in left ventricular end-systolic volume in patients undergoing algorithmic optimisation of CRT-D compared with usual device settings
Time frame: 24 weeks
End-systolic volume will be measured on echocardiography using Simpson's method. Where image quality precludes a full biplane assessment, single plane will be used with the apical 4-chamber view, or alternatively left ventricular end-systolic diameter will be used to calculate volume using the Teicholz method.
16 secondary outcomes
Feasibility of algorithmic, echocardiography-guided CRT-D optimisation with quadripolar left ventricular leads in clinical practice
Time frame: 24 weeks
Correlation between invasive haemodynamic studies with non-invasive ultrasound-based methods in optimising CRT-D
Time frame: 24 weeks
Change in left ventricular end diastolic pressure with algorithmic optimisation of CRT-D compared with usual device settings
Time frame: 24 weeks
Feasibility of ultrasound cardiac output monitoring (USCOM) in optimisation of CRT devices in clinical practice
Time frame: At baseline and at 12 weeks
Change in peak oxygen consumption with algorithmic CRT-D optimisation compared with usual device settings
Time frame: 24 weeks
Change in left ventricular ejection fraction with algorithmic CRT-D optimisation compared with usual device settings.
Time frame: 24 weeks
Change in left ventricular end-diastolic volume with algorithmic CRT-D optimisation compared with usual device settings.
Time frame: 24 weeks
Change in left ventricular diastolic filling time with algorithmic CRT-D optimisation compared with usual device settings.
Time frame: 24 weeks
Change in left ventricular outflow tract velocity time integral (LVOT VTI) with algorithmic CRT-D optimisation compared with usual device settings.
Time frame: 24 weeks
Change in longitudinal and global longitudinal strain (GLS) with algorithmic CRT-D optimisation compared with usual device settings.
Time frame: 24 weeks
Change in radial strain with algorithmic CRT-D optimisation compared with usual device settings.
Time frame: 24 weeks
Change in distance walked on a 6-minute hall walk test with algorithmic CRT-D optimisation compared with usual device settings
Time frame: 24 weeks
Change in New York Heart Association functional class with algorithmic CRT-D optimisation compared with usual device settings.
Time frame: 24 weeks
Change in score in the Minnesota Living with Heart Failure Questionnaire (MLHFQ) between algorithmically optimised CRT-D and usual device settings.
Time frame: 24 weeks
Change in cardiac output measured by the novel technique of Ultra-Sound Cardiac Output Monitoring (USCOM) with algorithmic CRT-D optimisation compared with usual device settings
Time frame: 24 weeks
Number of patients suffering adverse events during the study period
Time frame: From patient enrollment through study completion, an average of 1 year.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2020.
- Background: PubMed 12084604Auricchio A, Stellbrink C, Sack S, Block M, Vogt J, Bakker P, Huth C, Schondube F, Wolfhard U, Bocker D, Krahnefeld O, Kirkels H; Pacing Therapies in Congestive Heart Failure (PATH-CHF) Study Group. Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Cardiol. 2002 Jun 19;39(12):2026-33. doi: 10.1016/s0735-1097(02)01895-8.
- Background: PubMed 12063368Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, Ellestad M, Trupp RJ, Underwood J, Pickering F, Truex C, McAtee P, Messenger J; MIRACLE Study Group. Multicenter InSync Randomized Clinical Evaluation. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002 Jun 13;346(24):1845-53. doi: 10.1056/NEJMoa013168.
- Background: PubMed 12771115Young JB, Abraham WT, Smith AL, Leon AR, Lieberman R, Wilkoff B, Canby RC, Schroeder JS, Liem LB, Hall S, Wheelan K; Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial. JAMA. 2003 May 28;289(20):2685-94. doi: 10.1001/jama.289.20.2685.
- Background: PubMed 19800193Daubert C, Gold MR, Abraham WT, Ghio S, Hassager C, Goode G, Szili-Torok T, Linde C; REVERSE Study Group. Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. J Am Coll Cardiol. 2009 Nov 10;54(20):1837-46. doi: 10.1016/j.jacc.2009.08.011. Epub 2009 Oct 1.
- Background: PubMed 19038680Linde C, Abraham WT, Gold MR, St John Sutton M, Ghio S, Daubert C; REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) Study Group. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol. 2008 Dec 2;52(23):1834-1843. doi: 10.1016/j.jacc.2008.08.027. Epub 2008 Nov 7.
- Background: PubMed 20150328Chung ES, Katra RP, Ghio S, Bax J, Gerritse B, Hilpisch K, Peterson BJ, Feldman DS, Abraham WT. Cardiac resynchronization therapy may benefit patients with left ventricular ejection fraction >35%: a PROSPECT trial substudy. Eur J Heart Fail. 2010 Jun;12(6):581-7. doi: 10.1093/eurjhf/hfq009. Epub 2010 Feb 11.
- Background: PubMed 26333378Osca J, Alonso P, Cano O, Andres A, Miro V, Tello MJ, Olague J, Martinez L, Salvador A. The use of multisite left ventricular pacing via quadripolar lead improves acute haemodynamics and mechanical dyssynchrony assessed by radial strain speckle tracking: initial results. Europace. 2016 Apr;18(4):560-7. doi: 10.1093/europace/euv211. Epub 2015 Sep 1.
- Background: PubMed 25214507Rinaldi CA, Burri H, Thibault B, Curnis A, Rao A, Gras D, Sperzel J, Singh JP, Biffi M, Bordachar P, Leclercq C. A review of multisite pacing to achieve cardiac resynchronization therapy. Europace. 2015 Jan;17(1):7-17. doi: 10.1093/europace/euu197. Epub 2014 Sep 11.
- Background: PubMed 24291411Pappone C, Calovic Z, Vicedomini G, Cuko A, McSpadden LC, Ryu K, Romano E, Saviano M, Baldi M, Pappone A, Ciaccio C, Giannelli L, Ionescu B, Petretta A, Vitale R, Fundaliotis A, Tavazzi L, Santinelli V. Multipoint left ventricular pacing improves acute hemodynamic response assessed with pressure-volume loops in cardiac resynchronization therapy patients. Heart Rhythm. 2014 Mar;11(3):394-401. doi: 10.1016/j.hrthm.2013.11.023. Epub 2013 Nov 28.
- Background: PubMed 17241315Siu CW, Tse HF, Lee K, Chan HW, Chen WH, Yung C, Lee S, Lau CP. Cardiac resynchronization therapy optimization by ultrasonic cardiac output monitoring (USCOM) device. Pacing Clin Electrophysiol. 2007 Jan;30(1):50-5. doi: 10.1111/j.1540-8159.2007.00579.x.
- Background: PubMed 25625721Zanon F, Baracca E, Pastore G, Marcantoni L, Fraccaro C, Lanza D, Picariello C, Aggio S, Roncon L, Dell'Avvocata F, Rigatelli G, Pacetta D, Noventa F, Prinzen FW. Multipoint pacing by a left ventricular quadripolar lead improves the acute hemodynamic response to CRT compared with conventional biventricular pacing at any site. Heart Rhythm. 2015 May;12(5):975-81. doi: 10.1016/j.hrthm.2015.01.034. Epub 2015 Jan 24.
- Individual participant dataSharing planned: No. Individual participant data available on individual written request at the discretion of the investigators.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Freya M Lodge, MBBS principal investigator
Cardiff and Vale University Health Board
Zaheer R Yousef, MBBS study director
Cardiff and Vale University Health Board
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Algorithmic Cardiac Resynchronisation Therapy Optimisation in people with Heart Failure, Systolic, run by Cardiff and Vale University Health Board 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 1 inclusion and 3 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: withdrawn, as of the sponsor's last update on 22 Jan 2020. 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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in left ventricular end-systolic volume in patients undergoing algorithmic optimisation of CRT-D compared with usual device settings (time frame: 24 weeks). 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 NCT02997670, which also lists 11 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 22 Jan 2020.