Clinical trial NCT01417624: Cardiac Magnetic Resonance Imaging Guided Left Ventricular Lead Placement
Official title: The Assessment of Cardiac Magnetic Resonance Imaging Guided Left Ventricular Lead Placement During the Implantation of Cardiac Resynchronisation Therapy on Clinical Outcomes in Patients With Chronic Heart Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Heart Failure
Keywords: Heart Failure
Cardiac Resynchronisation Therapy
Lead sponsor: Royal Brompton & Harefield NHS Foundation Trust
Sponsor class: OTHER
First posted: 2011-08-16
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Heart failure is a common, costly, disabling and potentially lethal condition. Despite well recognised and proven drug therapies, many patients remain breathless on exertion. A special pacemaker (cardiac resynchronisation therapy) may help improve symptoms of breathlessness and survival by restoring coordinated beating of the heart. However, despite careful planning and the knowledge of the most appropriate selection criteria, up to a third of patients do not get the desired beneficial effects after the pacemaker has been implanted.

The implantation of the special pacemaker requires three leads (wires) to be inserted within the heart. Currently this is undertaken under X-ray guidance. Some patients may have scarring of the heart muscle due to previous heart attacks or their underlying condition. The X-ray technique cannot see this and therefore the doctor may implant the lead in such an area of scar tissue. Cardiac magnetic resonance imaging (CMR) can demonstrate these areas of scar. The study aims to investigate whether CMR can better predict where the wires should be placed. The CMR pictures will be taken before the patient has the special pacemaker implanted.

Detailed description: Cardiac Resynchronisation Therapy (CRT) is currently recommended for patients with heart failure who have symptomatic left ventricular (LV) systolic impairment and a prolonged QRS duration.1, 2 Up to a third of patients post CRT implantation do not derive the anticipated clinical benefit. The reasons for this are multifactorial, with patient selection and successful LV lead implantation likely to be key factors.

The mechanism by which CRT exerts its clinical benefits is fundamentally through the correction of mechanical dyssynchrony. However, despite much research in this area the optimal measures of dyssynchrony for the selection of suitable candidates for CRT have not been established. The current guidelines were revised in light of the PROSPECT trial which failed to prove validity and reproducibility in complex echocardiographic variables of dyssynchrony.3 The 12 lead electrocardiogram (ECG) remains the most widely used criterion for the assessment of dyssynchrony in patients being considered for CRT, with patients with a broad QRS complex (\>150ms) appearing to benefit the most.4, 5

Although the definition of left bundle branch block (LBBB) is well established, the precise electrophysiological characteristics remain poorly understood. An arbitrary 'cut off' of 120 milliseconds was recommended by the New York Heart Association (NYHA) in 1948 for its definition.6 This has subsequently become enshrined in the literature. The presence of LBBB, a heterogeneous entity, is associated with both electrical and mechanical abnormalities within the left ventricle.7 Septal and lateral wall delay frequently occur in this setting, with delayed activation of the lateral LV wall forming the basis for bi-ventricular pacing. It is well documented within populations with left ventricular impairment that there is prolongation of the QRS complex which is associated with an adverse prognosis.8

The success of CRT is reliant upon achieving an acceptable position of the left ventricular lead during implantation. The LV lead position needs to be anatomically stable to minimise the risk of lead displacement and also to avoid diaphragmatic capture. Furthermore, patients with myocardial scar tissue in the lateral LV segments as detected on CMR are known to have a worse outcome following CRT 9 and pacing such sites may potentially be pro-arrhythmic.10 It is not known whether CMR guided placement of the LV lead in order to avoid sites of myocardial scar and fibrosis can result in an improved clinical outcome in these patients.

A recently published study corroborates that myocardial scar in the region of activation of the LV lead may have a detrimental effect on the delivery of CRT. A consecutive series of 397 patients with ischaemic cardiomyopathy were imaged prior to the implantation of CRT. Using the complex echocardiographic technique of 'speckle tracking', myocardial scar was demonstrated to have an adverse effect on patients' outcomes. It remained an independent predictor of adverse clinical outcome. Notably due to the complexity of the technique, the presence of myocardial scar was validated using CMR.11

CRT response is a contentious subject. It is well recognised within the literature that approximately 30-40% of patients do not appear to improve clinically following CRT implantation.12 However, the inter-study variability of what has been considered as a marker of response has been wide and several different variables have been utilised.13 Several of the studies have also been small, single centre, and non-randomised. There is currently a lack of consensus in what constitutes 'response' vs 'non-response' following CRT, which may be either defined in terms of markers of LV reverse remodelling or changes in the clinical indices of heart failure or a combination of them both. In an effort to rationalise the endpoints of CRT trials, clinical composite scores have been devised inclusive of both imaging based and clinical endpoints. However, the correlation between both LV remodelling and clinical endpoints when compared using correlation coefficients is marginally better than chance. The realisation that clinical improvement post CRT implantation does not necessarily accompany mechanical remodelling has also confused the issue.

Rationale for Study The aim of the present study is to provide pilot data, the results of which should increase our understanding of the mechanisms by which CRT improves clinical outcomes in patients with heart failure.

Eligibility criteria: Inclusion Criteria:

* Able to give written informed consent
* Age \>18 years old
* Successful CRT implantation (with or without a defibrillator)
* NYHA Class III-IV Heart Failure (or NYHA II with NYHA III/IV symptoms in the preceding 12 months)
* LVEF \<35% (Calculated using echocardiography or Cardiac MR) at the time of implantation
* QRS duration \> 120ms with Left Bundle Branch Block morphology on ECG
* Sinus Rhythm
* Optimal Tolerated Medical Therapy for Heart Failure

Exclusion Criteria:

* Severe, life threatening non cardiac disease
* Active malignant disease and recent (\<5 years) malignant disease
* Prior Heart Transplant
* Recent history of unstable angina, acute coronary syndrome or myocardial infarction within three months of enrollment into the study
* Pregnancy
* Failure to participate in consent process
* Atrial Fibrillation
* Conventional pacemaker in situ
* Heart Failure requiring constant intravenous therapy including diuretics and/or inotropes
* Recent revascularisation procedure i.e. coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) within the last three months
* Contraindications to a CMR study

Primary outcomes:
measure: 6 Minute Walk Test Distance
timeFrame: 12 months
Secondary outcomes:
measure: Exercise Tolerance (MVO2)
timeFrame: 6, 12 months following CRT Implantation
measure: Blood Tests - Serum BNP
timeFrame: 1, 6, 12 months following CRT Implantation
measure: Clinical -NYHA Classification
timeFrame: 1, 6, 12 months following CRT
measure: Quality of Life Questionnaires
timeFrame: 1,6,12 months following CRT Implantation
measure: Echocardiography
timeFrame: 1,6,12 months following CRT Implantation
measure: Pacing
timeFrame: 1,6,12 months following CRT Implantation
measure: Blood Test -Urate
timeFrame: 1,6,12 months following CRT Implantation
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
affiliation: Royal Brompton & Harefield NHS Foundation Trust
name: Rakesh Sharma, MRCP PhD
role: PRINCIPAL_INVESTIGATOR
References: