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Cardiac Magnetic Resonance Imaging Guided Left Ventricular Lead Placement

15 sierpnia 2011 zaktualizowane przez: Royal Brompton & Harefield NHS Foundation Trust

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

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.

Przegląd badań

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Oczekiwany)

70

Faza

  • Faza 3

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

      • London, Zjednoczone Królestwo, SW3 6NP
        • Rekrutacyjny
        • Royal Brompton Hospital
        • Główny śledczy:
          • Rakesh Sharma, MRCP PhD
        • Pod-śledczy:
          • Kaushik Guha, MBBS MRCP
        • Pod-śledczy:
          • Martin R Cowie, MD FRCP FESC
        • Pod-śledczy:
          • Raad Mohiaddin, MD PhD FRCP
        • Pod-śledczy:
          • Ranil de Silva, PhD FRCP

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat do 90 lat (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Diagnostyczny
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Komparator placebo: Control Group - Standard

This will be a randomised controlled unblinded prospective study recruiting patients in sinus rhythm with LBBB (QRS width ≥ 120ms) and a LV ejection fraction of below 35% who meet the current guidelines for CRT implantation. Patients will be randomised to one of two groups (1:1 randomisation)

Conventional LV lead placement - the LV lead will be placed according to standard techniques without knowledge of the patient's CMR findings

Following randomisation, the optimal position of the LV lead will be determined either according to current standard criteria (as proposed by the primary operator) or with CMR guidance.

The CRT device will be implanted using established conventional techniques. The CMR study will be performed pre-implantation only. The distribution of myocardial scar and fibrosis will be derived from this study. A CMR venogram will also be generated and the suggested optimal venous tributaries of the great cardiac vein will be identified from discussion between the principal investigator and senior CMR physician. This information will be used for those in the active arm only.

Inne nazwy:
  • A cardiac Magnetic resonance Scan using Gadolinium Contrast
Aktywny komparator: Active CMR guided Arm

This will be a randomised controlled unblinded prospective study recruiting patients in sinus rhythm with LBBB (QRS width ≥ 120ms) and a LV ejection fraction of below 35% who meet the current guidelines for CRT implantation.Patients will be randomised to one of two groups (1:1 randomisation):

CMR guided LV lead placement - an expert panel will decide pre-operatively the optimal branch of the coronary sinus for LV lead placement based on the presence of myocardial scar tissue and coronary sinus anatomy. The operator will informed as to the optimal vein to target for delivery of the LV lead. Should this be technically unfeasible (e.g. due to pacing considerations or stability of LV lead position), then the most suitable vein will be used at the time of implantation.

Following randomisation, the optimal position of the LV lead will be determined either according to current standard criteria (as proposed by the primary operator) or with CMR guidance.

The CRT device will be implanted using established conventional techniques. The CMR study will be performed pre-implantation only. The distribution of myocardial scar and fibrosis will be derived from this study. A CMR venogram will also be generated and the suggested optimal venous tributaries of the great cardiac vein will be identified from discussion between the principal investigator and senior CMR physician. This information will be used for those in the active arm only.

Inne nazwy:
  • A cardiac Magnetic resonance Scan using Gadolinium Contrast

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
6 Minute Walk Test Distance
Ramy czasowe: 12 months
CMR guided LV lead placement during CRT implantation results in improved exercise tolerance at 12 months in patients with heart failure.
12 months

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Exercise Tolerance (MVO2)
Ramy czasowe: 6, 12 months following CRT Implantation
Cardiopulmonary Exercise Testing (Peak Oxygen Consumption, MVO2)
6, 12 months following CRT Implantation
Blood Tests - Serum BNP
Ramy czasowe: 1, 6, 12 months following CRT Implantation
• B Type Natriuretic Peptide (BNP)
1, 6, 12 months following CRT Implantation
Clinical -NYHA Classification
Ramy czasowe: 1, 6, 12 months following CRT
NYHA Classification
1, 6, 12 months following CRT
Quality of Life Questionnaires
Ramy czasowe: 1,6,12 months following CRT Implantation
Euroqol and Minnesota Quality of Life Questionnaires for HF
1,6,12 months following CRT Implantation
Echocardiography
Ramy czasowe: 1,6,12 months following CRT Implantation
LVEF, LVEDD, LVESD, LVESV, LVEDV
1,6,12 months following CRT Implantation
Pacing
Ramy czasowe: 1,6,12 months following CRT Implantation
Level of Bi Ventricular Pacing and atrial and ventricular arrythmia burden
1,6,12 months following CRT Implantation
Blood Test -Urate
Ramy czasowe: 1,6,12 months following CRT Implantation
Serum Urate
1,6,12 months following CRT Implantation

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Śledczy

  • Główny śledczy: Rakesh Sharma, MRCP PhD, Royal Brompton & Harefield NHS Foundation Trust

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów

1 sierpnia 2011

Zakończenie podstawowe (Oczekiwany)

1 grudnia 2012

Ukończenie studiów (Oczekiwany)

1 czerwca 2013

Daty rejestracji na studia

Pierwszy przesłany

11 sierpnia 2011

Pierwszy przesłany, który spełnia kryteria kontroli jakości

15 sierpnia 2011

Pierwszy wysłany (Oszacować)

16 sierpnia 2011

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Oszacować)

16 sierpnia 2011

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

15 sierpnia 2011

Ostatnia weryfikacja

1 sierpnia 2011

Więcej informacji

Terminy związane z tym badaniem

Inne numery identyfikacyjne badania

  • RBH2011HS008B

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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