Quantification of lung water in heart failure using cardiovascular magnetic resonance imaging

Abstract

Background: Pulmonary edema is a cardinal feature of heart failure but no quantitative tests are available in clinical practice. The goals of this study were to develop a simple cardiovascular magnetic resonance (CMR) approach for lung water quantification, to correlate CMR derived lung water with intra-cardiac pressures and to determine its prognostic significance.

Methods: Lung water density (LWD, %) was measured using a widely available single-shot fast spin-echo acquisition in two study cohorts. Validation Cohort: LWD was compared to left ventricular end-diastolic pressure or pulmonary capillary wedge pressure in 19 patients with heart failure undergoing cardiac catheterization. Prospective Cohort: LWD was measured in 256 subjects, including 121 with heart failure, 82 at-risk for heart failure and 53 healthy controls. Clinical outcomes were evaluated up to 1 year.

Results: Within the validation cohort, CMR LWD correlated to invasively measured left-sided filling pressures (R = 0.8, p < 0.05). In the prospective cohort, mean LWD was 16.6 ± 2.1% in controls, 17.9 ± 3.0% in patients at-risk and 19.3 ± 5.4% in patients with heart failure, p < 0.001. In patients with or at-risk for heart failure, LWD > 20.8% (mean + 2 standard deviations of healthy controls) was an independent predictor of death, hospitalization or emergency department visit within 1 year, hazard ratio 2.4 (1.1-5.1, p = 0.03).

Conclusions: In patients with heart failure, increased CMR-derived lung water is associated with increased intra-cardiac filling pressures, and predicts 1 year outcomes. LWD could be incorporated in standard CMR scans.

Keywords: Heart failure; Lung water; MRI.

Fig. 1

Method for imaging lung water. a) Prescription of sagittal slices on a dark blood axial localizer image. Six of 12 slices locations are shown. b) Half-Fourier single shot turbo spin echo (HASTE) images acquired during free-breathing at each of the six slice locations with the image closest to end-expiration indicated by a red border. c) User-selected regions of interest on the end-expiration images include a tracing of the lung region and a liver region

Fig. 2

Rectangular profile method for imaging lung water density. The region of interest (10 mm × 180 mm) from which a profile signal intensity is calculated over a central slice in the right lung and liver. A sample signal intensity profile is shown on the right (arbitrary units), showing the relative signal intensities in the lung and liver, and as compared to a noise region, outside of the body

Fig. 3

Sample lung water density images. Comparison of lung water density in a healthy control and patient with heart failure after removal of blood vessels and insertion of missing pixels using linear interpolation. Using the rectangular profile analysis method (Fig. 2), the lung water density was 16.5% in the control subject and 27.1% in the patient. The patient had an elevated left ventricular end-diastolic pressure of 31 mmHg (normal ≤12 mmHg) on cardiac catheterization and a brain naturetic peptice (BNP) of 1467 pg/ml (normal < 100 pg/ml)

Fig. 4

Comparison of lung water density and BNP with filling pressures. Comparison of left sided filling pressures with a) BNP, and with CMR derived lung water in the left lung (b), the right lung (c), the whole lung (d) and with the profile method in the right lung (e). p < 0.05 for each comparison

Fig. 5

Summary of lung water density using the rectangular profile method in all subjects from the Prospective Cohort. A dashed line, at 20.8%, indicates the upper limit of normal lung water density defined as mean + 2 standard deviations from the Healthy Control group. Each circle is an individual subject with gray denoting individuals above the normal threshold. Box plots for each group show the median, 25th and 75th percentiles and the whiskers show the extent of the data, with red crosses for outliers. Groups with increased lung water, *p < 0.05 in comparison with Healthy Control and At-Risk groups, **p < 0.05 in comparison with Healthy Control, At-Risk and NYHA I/II groups. Abbreviations – HF: heart failure, HFpEF: heart failure with preserved ejection fraction, HFrEF: heart failure with reduced ejection fraction, NYHA: New York Heart Association Classification

Fig. 6

Kaplan-Meier survival curves for 203 patients with or at-risk for heart failure from the Prospective Cohort stratified by lung water density (Panel a – Cardiovascular Events, Panel b – Heart Failure Events). Abbreviations - LWD: lung water density