Lung Water Density Is Increased in Patients at Risk of Heart Failure and Is Largely Independent of Conventional CMR Measures

Aims: Non-invasive methods to quantify pulmonary congestion are lacking in clinical practice. Cardiovascular magnetic resonance (CMR) lung water density (LWD) mapping is accurate, reproducible, and has prognostic value. However, it is not known whether LWD is associated with routinely acquired CMR parameters. Methods and Results: This was a prospective, observational cohort including healthy controls and patients at risk of heart failure. Lung water density was measured using CMR with a free-breathing short echo time 3D cartesian gradient-echo sequence with a respiratory navigator at 1.5T. Associations were assessed between LWD, lung water volume (LWV) and cardiac volumes, left ventricular (LV) mass and function, myocardial native T1 and extracellular volume fraction (ECV). In patients at risk for heart failure (n=155), LWD was greater than in healthy controls (n=15) (30.4±5.0 vs 27.2±4.3%, p=0.02). Using receiver operating characteristic analysis, the optimal cut-off for LWD was 27.6% to detect at-risk patients (sensitivity 72%, specificity 73%, positive likelihood ratio 2.7, inverse negative likelihood ratio 2.6). LWD was univariably associated with body mass index (BMI), hypertension, right atrial (RA) area and LV mass (p<0.05 for all). In multivariable linear regression, only BMI remained associated with LWD (R2=0.32, p<0.001). In a separate multivariable analysis including only CMR markers, only RA area remained associated with LWD (R2=0.05, p=0.006). Conclusion: LWD is increased in patients at risk for heart failure compared to controls, and is only weakly explained by conventional CMR measures. LWD provides diagnostic information which is largely independent of conventional CMR measures. ### Competing Interest Statement MU is principal investigator for an institutional research and development agreement regarding cardiovascular magnetic resonance imaging between Karolinska University Hospital and Siemens. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Singapore Health Services (SingHealth) gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets generated and analysed for the current study are not publicly available. Please contact the corresponding author for data requests.