In this sample of subjects without clinical history of cardiovascular disease drawn from a general population, we found that several MRI-based cardiac parameters were associated with lung volumes derived from pulmonary function tests. Interestingly, MRI-based cardiac parameters were inversely associated with MRI-based lung volumes. We observed a notable relationship of FEV1, FVC, and residual volume determined by PFT as well as MRI-based lung volumes with selected cardiac measures.
Firstly, we observed an association between end-diastolic and end-systolic volumes, and stroke volume for both LV and RV with FEV1 and FVC, as well as with peak ejection rate, and early diastolic filling rate; additionally, late diastolic filling rate showed an association with FVC. No associations were seen between cardiac parameters and the Tiffeneau index. Secondly, there were significant relationships between LV end-diastolic volume, RV stroke volume, peak ejection rate, and early and late diastolic filling rate, with residual volume. For PFT, our results are consistent with the recent findings from Thomson et al. who showed, using the UK Biobank data, that lower FEV1 and FVC were associated with smaller LV end-diastolic, end-systolic, and stroke volumes, as well as RV end-diastolic, end-systolic, and stroke volumes [13]. Like the UK Biobank, our cohort included only subjects with no history of cardiovascular disease. Comparing the effect size, the estimates in our cohort were significantly larger compared to those in the UK Biobank study. For example, Thomson et al. reported a change of LV end-diastolic volume of -5.69 mL per SD in FVC, while we observed a change of -12.51 mL per SD in FVC (one SD of FVC was 1.039L in our cohort). Thomson et al. also observed a change of RV end-diastolic volume of -5.84 mL per SD in FVC, while we observed a change of -12.56 ml per SD in FVC, plausibly due to higher body weights in our cohort. However, comparison with the actual PFT parameters was not possible, as these were not reported in the recent publication of the UK Biobank study. Our study adds to the findings of the UK Biobank by showing that FEV1 and FVC may not only affect end-diastolic volumes, but also the diastolic filling rates, which has not been reported so far. We also observed a correlation between the late diastolic filling rate and residual volume, suggesting the impact of residual volume on increased left atrial filling pressures and left atrial contractile function. To our knowledge, this study is the first to describe an inverse association of lung volume with the early diastolic filling rate derived from whole-body MR scans.
With respect to the lung volume derived from whole-body MRI, stroke volume was inversely associated for both LV and RV. For the LV, end-diastolic volume was inversely related; the early, but not the late diastolic filling rate, was inversely related to MRI-based lung volume. Overall, we observed a significant inverse association between lung assessment by MRI and cardiac parameters, in contrast with lung assessment by PFT.
MRI-derived lung volume shows a good correlation with residual volume (r = 0.57) and is independently associated with obstructive ventilatory impairment, based on PFT measurements (Tiffeneau index) and clinical presentation [15]. Whereas the Tiffeneau index is the established parameter to define bronchial obstruction, residual volume can be an indicator of hyperinflation in obstructive lung diseases, and has a unique prognostic value in COPD patients [24].
However, the inverse association between cardiac parameters and MRI-based lung volume contrasted with the positive associations between cardiac parameters and PFT. More specifically, in subjects with both LV end-diastolic volume and early LV diastolic filling decrease, we observed an increased MRI-based lung volume. Again, both cardiac parameters increase with increased residual volume (similarly for FEV1 and FVC). Therefore, this finding may indicate, that pathophysiological characteristics not captured by PFT potentially can be further evaluated through MRI-based assessment of lung volumes. Several mechanisms could explain the contradictory findings between PFT and imaging-based lung assessment in association with cardiac parameters. Breathing mechanics are a likely explanation. PFTs follow a standardized procedure to evaluate lung function and obstructive pulmonary disease, while subjects examined by MRI are often not required to conform to any specific breathing regimen. Additionally, altered breathing patterns, while performing PFT, may occur in subjects with subclinical emphysema. Furthermore, the body posture during measurement should be considered. Subjects are examined in an upright sitting position during PFT, while MRI is performed in supine position. Differences in body position can cause substantial changes in observed lung volumes, including functional residual capacity and residual volume. Moreover, mechanical pressures of the thorax mechanics may be differently affected by body posture in subjects depending on the amount of abdominal fat. Still, imaging can provide pathophysiological insights beyond PFTs for the assessment of ventilatory impairment and lung diseases.
Our findings are supported by previous evidence, as an inverse association between clinically diagnosed severe emphysema and end-diastolic volume for LV measured by cine MRI was described earlier, despite the relatively small number of patients with emphysema (n = 24) [6]. Our results also showed early LV filling impairment and low stroke volumes for both LV and RV, with no change in ejection fraction, in association with lung volume. This is consistent with previous studies where lung volumes were determined by CT and related cine MRI parameters [7, 8], or ECG-gated CT angiography [25]. Also, peak LV filling rates in early and late diastole can be derived from rates of change in chamber volume - a technique made possible by the high spatial resolution of cine MRI (Fig. 1). The peak early and late filling rate in LV are sensitive markers and can indicate early subclinical diastolic dysfunction [26]. However, measuring these volume-derived indices can be a time-consuming process even with advanced software, and therefore impractical in routine clinical care [27]. LV diastolic function indices derived from whole-body MRI may have a future role in screening for early subclinical diastolic, especially if coupled with machine learning techniques.
One strength of our study is the use of an advanced MRI technology 3-Tesla generation, which includes the most advanced imaging modality to-date with well-defined imaging protocol, image processing, and detailed information on the health condition of the study population. Previous studies quantified the lung volumes using CT, which contains radiation-exposure. The lung volume assessment using MRI provides an alternative radiation-free method for large-scale imaging studies. However, our study contains limitations which should be considered. Firstly, our study is a cross-sectional analysis design and therefore does not allow to assess relationships between alterations in pulmonary and cardiac parameters over time. Secondly, although our sample size included about 400 subjects, this number is relatively small due to the laborious nature of image processing of whole-body MRI assessment. However, the findings observed in our sample may represent important information for hypothesis generation. Thirdly, in our sample, only Caucasian participants with no history of cardiovascular disease were included, which may limit the generalizability of our findings.