Summary Rationale: Cardiac resynchronisation therapy (CRT) with biventricular pacemakers and implantable cardiac defibrillators (ICD) has proven to be a valuable therapy in selected patients with systolic heart failure, ameliorating both morbidity and mortality. However, with current selection criteria and implant technique, about 20 to 30 % of patients remain non-responders. Non-responders might be due to failing selection criteria or methodology in casu echocardiography. Moreover, the definition of response to CRT is unequivocal and there is a need for a simple and reproducible measure of response with low inter- and intra-observer variability.

Primary objectives: This study evaluates the correlation between intrathoracic blood volume (ITBV) measured by contrast enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI), as well as the feasibility to use intrathoracic blood volume as a predictor for response to CRT.

Study design: a prospective nonrandomized pilot study Study population: patients with heart failure New York Heart Association (NYHA) class III or IV, a left ventricular ejection fraction equal to or less than 35% and a QRS-duration equal to or more than 0.12 seconds who are referred to our centre for implantation of a CRT-P or CRT-D device.

Intervention: No specific intervention will be performed. Main study parameters: correlation between intrathoracic bloodvolume measured by CEUS and MRI, correlation between LVEF measured by CEUS and by standard 2D ultrasound (biplane methods of discs), change in intrathoracic blood volume as a response to CRT.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: at baseline a clinical examination, laboratory analysis, cardiopulmonary exercise testing, echocardiography and cardiac magnetic resonance imaging will be performed. All of these examinations will be repeated at 3-months follow-up except for the cardiac magnetic resonance imaging. All examinations, except for the MRI, are part of the standard workup in our hospital for patients undergoing implantation of a CRT device. Data needed for the purpose of this study, will be acquired by offline image analysis with dedicated software.

Inclusion Criteria:

1. Age ≥18y
2. LVEF ≤35%
3. QRS-duration ≥0.12 seconds
4. NYHA functional class III or IV despite optimal medical therapy defined as use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor blocker and beta-blockers unless they are not tolerated or contra-indicated
5. sinus rhythm or atrial fibrillation

Exclusion Criteria:

1. episode of acute heart failure ≤3 months
2. change in dosage of beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers ≤3 months
3. unstable angina pectoris, acute myocardial infarction, percutaneous intervention or coronary bypass surgery ≤3 months
4. chronic atrial arrhythmias other than atrial fibrillation
5. any mechanical or biological valve prosthesis
6. atrial septal defect
7. right-to-left shunt
8. severe pulmonary hypertension (systolic pulmonary artery pressure >90 mmHg)
9. uncontrolled arterial hypertension
10. known allergy to sulphur hexafluoride
11. end-stage renal or hepatic disease
12. inability to provide written informed consent
13. pregnancy or childbearing potential without use of birth-control measurements
14. general contra-indications to magnetic resonance imaging

All patients referred to our centre for implantation of a CRT-P or CRT-D device are eligible. In the pilot phase 20 patients will be included. Data will be collected at baseline and 3 months post-implantation.