Clinical trial NCT03495505: CT Guided WiSE-CRT
Official title: Image Optimisation and Guidance for Wireless Endocardial Cardiac Resynchronisation Therapy: The CT Guided Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Keywords: WiSE-CRT
Endocardial Pacing Optimisation
Cardiac Resynchronisation Therapy
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2018-04-12
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 20 patients will be recruited into this feasibility study with a 6 month follow-up. There will be no blinding nor randomisation.
Primary purpose: TREATMENT

Brief summary: This feasibility study will use CT scanning to identify the optimal location for placement of the WiSE-CRT system.

Detailed description: Heart failure (HF) is estimated to affect at least 10% of adults aged over 70 years old, with a 12-month all-cause mortality rate of 7% in stable patients. Cardiac resynchronisation therapy (CRT) is an important intervention for patients with severe left ventricular (LV) systolic impairment and helps to improve well-being and reduce morbidity and mortality. CRT is achieved by placing endocardial pacing leads into the right atrium and right ventricle and then placing a third pacing lead through the coronary sinus (CS) to enable epicardial LV pacing, thus achieving ventricular resynchronisation. Although this is a successful therapy, overall 30-40% of patients will fail to respond. Additionally, even in those eligible for CRT, approximately 8-10% of patients cannot have it implanted due to anatomical abnormalities such as venous occlusion, inappropriate CS targets, diffuse scar resulting in inappropriately high pacing thresholds or phrenic nerve stimulation. In these circumstances other avenues to achieve biventricular pacing needs to be sought.

The wireless CRT system (WiSE-CRT, EBR Systems) has been developed to overcome these issues. It uses an endocardial LV electrode to achieve biventricular pacing negating the need to implant a pacing lead through the CS. There are several advantages of endocardial LV pacing such as a greater selection of pacing sites, possibility of lower pacing outputs compared with conventional leads in the CS and it appears to be a more physiological way to pace. The WiSE-CRT system is used in conjunction with a single or dual-chamber pacemaker and is made up of several components. A transmitter is implanted subcutaneously, attached to a battery. This detects right ventricular pacing from the co-implant and then delivers ultrasonic energy which is received by an electrode placed in the LV endocardium to enable biventricular pacing. The transmitter must be placed in a position with an adequate "acoustic window," which requires a line from the transmitter to the LV that is free of significant tissue or bone. Additionally, the endocardial electrode must be placed in close proximity to the transmitter. In a study of 35 patients, the WiSE-CRT system was successful implanted in 97.1% of cases, with 97% achieving biventricular pacing at 1 month and 84.8% showing an improvement in the clinical composite score at 6 months. These results are particularly encouraging given the device was used in patients who had failed conventional CRT, representing a difficult patient group.

The major advantage of the WiSE-CRT system is that the LV electrode can be placed anywhere within the ventricle. Studies have shown that patient outcomes are improved by pacing at a site which avoids ventricular scar and targets an area of latest mechanical activation. These sites will vary according to the aetiology underlying HF. In addition, using conventional fluoroscopy to guide pacing lead implants has been shown to be inaccurate when compared with computed tomography (CT). Our group have previously shown that magnetic resonance imaging (MRI) can be overlaid on fluoroscopic images to help guide epicardial pacing to a specific location and improve outcomes. Many patients undergoing a WiSE-CRT implant will be unable to have a MRI due to their previous pacemaker implant. However, guidance may still be achieved using CT scanning.

The proximity and orientation of the transmitter to the endocardial electrode is important in determining the battery life of the WiSE-CRT system. Yeh et al. showed that a large proportion of patients have at least two suitable acoustic windows for placement of the transmitter. This provides the operator with more opportunities to carefully select an ideal location. However, once implanted the endocardial electrode must be placed within the acoustic window which limits the number of sites the electrode can then be placed.

Identifying the best location for both the transmitter and endocardial electrode is essential to target the most viable myocardium and improve patient outcomes. Ideally this should be achieved before the patient has undergone any procedure since implanting the transmitter limits the potential locations for the electrode. We believe CT guidance can provide satisfactory information to optimise the location for both the transmitter and electrode which will increase the patient response rate and improve outcomes.

Eligibility criteria: Inclusion Criteria:

* Age ≥18
* Ability to provide informed consent to participate and willing to comply with the clinical investigation plan and follow-up schedule.
* Patients with pre-existing permanent pacing systems in situ.
* Left ventricular systolic impairment with ejection fraction of \<45%
* Clinical symptoms of heart failure despite optimal medical therapy (NYHA II- IV)
* QRS duration \>120ms on surface ECG

Exclusion Criteria:

* Creatinine clearance \<30mls/minute (GFR)
* Severe allergy to contrast medium or severe asthma/ COPD
* Life expectancy \<1 year
* Significant aortic valve disease or prosthesis
* Significant mitral regurgitation
* Significant peripheral vascular disease
* Contraindication to anticoagulation therapy
* Insufficient acoustic window to the LV as assessed from diagnostic transthoracic echocardiography
* Left atrial or ventricular thrombus

Primary outcomes:
measure: Change in acute haemodynamic response (dp/dt) during the procedure
timeFrame: Baseline and during procedure
Secondary outcomes:
measure: Change in Minnesota Living with Heart Failure Questionnaire Score
timeFrame: Baseline and 6 months
measure: Evidence of reverse remodelling (≥15% improvement in end systolic volume) on transthoracic echocardiogram at 6 months post CRT implantation
timeFrame: Baseline and 6 months
measure: Change in 6 minute walk test
timeFrame: Baseline and 6 months
measure: Change in cardio-pulmonary exercise test score
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guys and St Thomas' NHS Foundation Trust
Study officials:
affiliation: King's College London
name: Steven Niederer, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016 Jul 14;37(27):2129-2200. doi: 10.1093/eurheartj/ehw128. Epub 2016 May 20. No abstract available.
citation: Reddy VY, Miller MA, Neuzil P, Sogaard P, Butter C, Seifert M, Delnoy PP, van Erven L, Schalji M, Boersma LVA, Riahi S. Cardiac Resynchronization Therapy With Wireless Left Ventricular Endocardial Pacing: The SELECT-LV Study. J Am Coll Cardiol. 2017 May 2;69(17):2119-2129. doi: 10.1016/j.jacc.2017.02.059.
citation: Ypenburg C, van Bommel RJ, Delgado V, Mollema SA, Bleeker GB, Boersma E, Schalij MJ, Bax JJ. Optimal left ventricular lead position predicts reverse remodeling and survival after cardiac resynchronization therapy. J Am Coll Cardiol. 2008 Oct 21;52(17):1402-9. doi: 10.1016/j.jacc.2008.06.046.
citation: Miller MA, Neuzil P, Dukkipati SR, Reddy VY. Leadless Cardiac Pacemakers: Back to the Future. J Am Coll Cardiol. 2015 Sep 8;66(10):1179-89. doi: 10.1016/j.jacc.2015.06.1081.