evaluation of mri measures of lung water with posture changes in healthy volunteers and in patients with cardiac failure

Conditions: Heart Failure, Congestive

Summary: 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

Keywords: lung water measures pulmonary edema mri heart failure