Evaluation of MRI Measures of Lung Water With Posture Changes in Healthy Volunteers and in Patients With Cardiac Failure

The aim of this study is to establish a model for the evaluation of drug targets using postural measures to induce changes in lung water concentration as assessed by MRI. A reduction in the magnitude and rate of water transudation with postural changes in patients with congestive heart failure (CHF) could provide a model for the evaluation of various classes of molecules for target validation and for dose selection.


Eligibility Criteria:
Inclusion Criteria:

* Heart Failure Patients:
* Established diagnosis of mild to moderate heart failure of any aetiology with symptoms defined as corresponding to the New York Heart Association (NYHA) class I, II or III
* Able in the opinion of the patient and investigator to be supine for 1 hour and to experience passive leg raising (PLR) whilst in the MRI scanner
* Male or female over 18 years of age at the time of signing the informed consent
* Negative urine or serum pregnancy test
* Capable of giving written informed consent
* Registered with a UK general practitioner.
* Participants must read (in English) at a level sufficient to adequately complete study related questionnaires
* Able to understand and comply with protocol requirements, instructions and protocol-stated restrictions
* Healthy Volunteers:
* Healthy as determined by a responsible physician
* Male or female over 18 years of age at the time of signing the informed consent
* Capable of giving written informed consent
* Negative urine or serum pregnancy test
* Registered with a UK general practitioner
* Participants must read (in English) at a level sufficient to adequately complete study related questionnaires
* Able to understand and comply with protocol requirements, instructions and protocol-stated restrictions

Exclusion Criteria:

* Heart Failure Patients
* History of primary pulmonary disease requiring current medication or other therapy.
* Orthopnoea of sufficient severity to preclude supine scanning.
* Hip or leg pathology of sufficient severity to prevent extension of both legs to 45 degrees.
* Unstable heart failure, defined as change in NYHA status, change in heart failure therapy regimen or hospitalization for acute decompensation of heart failure within preceding 6 weeks.
* Unstable angina within the past 3 months
* Current smoker, defined as having smoked in the preceding 1 year
* Uncontrolled hypertension (resting systolic BP \> 160 mmHg or resting diastolic BP \> 100mmHg)
* Resting hypoxia (SaO2 \<93%).
* Contraindication to MRI scanning
* Pregnant females
* Positive drugs of abuse or alcohol screen.
* Unwillingness or inability to follow the procedures outlined in the protocol.
* Healthy Volunteers
* History of primary pulmonary disease requiring current medication or other therapy
* Current smoker, defined as having smoked in the preceding 1 year
* Hip or leg pathology of sufficient severity to prevent extension of both legs to 45 degrees
* Contraindication to MRI scanning
* Pregnant females
* Positive drugs of abuse or alcohol screen
* Unwillingness or inability to follow the procedures outlined in the protocol