Clinical trial NCT02997670: Quartet Lead With Defibrillator Multisite Algorithmic Cardiac Resynchronisation Therapy Optimisation
Official title: Quartet Lead With Defibrillator Multisite Algorithmic Cardiac Resynchronisation Therapy Optimisation
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Heart Failure, Systolic
Keywords: Cardiac resynchronization pacing therapy
Lead sponsor: Cardiff and Vale University Health Board
Sponsor class: OTHER_GOV
Collaborators: name: Abbott Medical Devices
First posted: 2016-12-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* Successful implantation of CRT-D device with quadripolar left ventricular lead and dual coil right ventricular lead.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change in left ventricular end-systolic volume in patients undergoing algorithmic optimisation of CRT-D compared with usual device settings
timeFrame: 24 weeks
Secondary outcomes:
measure: Feasibility of algorithmic, echocardiography-guided CRT-D optimisation with quadripolar left ventricular leads in clinical practice
timeFrame: 24 weeks
measure: Correlation between invasive haemodynamic studies with non-invasive ultrasound-based methods in optimising CRT-D
timeFrame: 24 weeks
measure: Change in left ventricular end diastolic pressure with algorithmic optimisation of CRT-D compared with usual device settings
timeFrame: 24 weeks
measure: Feasibility of ultrasound cardiac output monitoring (USCOM) in optimisation of CRT devices in clinical practice
timeFrame: At baseline and at 12 weeks
measure: Change in peak oxygen consumption with algorithmic CRT-D optimisation compared with usual device settings
timeFrame: 24 weeks
measure: Change in left ventricular ejection fraction with algorithmic CRT-D optimisation compared with usual device settings.
timeFrame: 24 weeks
measure: Change in left ventricular end-diastolic volume with algorithmic CRT-D optimisation compared with usual device settings.
timeFrame: 24 weeks
measure: Change in left ventricular diastolic filling time with algorithmic CRT-D optimisation compared with usual device settings.
timeFrame: 24 weeks
measure: Change in left ventricular outflow tract velocity time integral (LVOT VTI) with algorithmic CRT-D optimisation compared with usual device settings.
timeFrame: 24 weeks
measure: Change in longitudinal and global longitudinal strain (GLS) with algorithmic CRT-D optimisation compared with usual device settings.
timeFrame: 24 weeks
measure: Change in radial strain with algorithmic CRT-D optimisation compared with usual device settings.
timeFrame: 24 weeks
measure: Change in distance walked on a 6-minute hall walk test with algorithmic CRT-D optimisation compared with usual device settings
timeFrame: 24 weeks
measure: Change in New York Heart Association functional class with algorithmic CRT-D optimisation compared with usual device settings.
timeFrame: 24 weeks
measure: Change in score in the Minnesota Living with Heart Failure Questionnaire (MLHFQ) between algorithmically optimised CRT-D and usual device settings.
timeFrame: 24 weeks
measure: 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
timeFrame: 24 weeks
measure: Number of patients suffering adverse events during the study period
timeFrame: From patient enrollment through study completion, an average of 1 year.
Other outcomes:
Locations:
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
Study officials:
affiliation: Cardiff and Vale University Health Board
name: Freya M Lodge, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Cardiff and Vale University Health Board
name: Zaheer R Yousef, MBBS
role: STUDY_DIRECTOR
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