Discussion
We compared diastolic and systolic IVPDs between subjects with HFrEF, HFpEF or No-HF. We found physiologically expected patterns of IVPD in all three groups, with significant differences in diastolic IVPDs. Specifically, subjects with HFpEF exhibited more pronounced reversal peak of early diastolic IVPDs, which was independent of clinical parameters, echocardiographic parameters of LV filling, and LV structure assessed by MRI. Subjects with HFrEF demonstrated a non-significant trend of increasing E-IVPD and decreasing A-IVPD, S-IVPD and SR-IVPD. Our findings suggest distinct patterns of systolic and diastolic IVPDs and differences in the nature of both diastolic and systolic dysfunction between HF subtypes. IVPD parameters demonstrated only weak correlations with standard Doppler-echocardiographic parameters.
Previous studies have shown that, despite being small in magnitude, IVPDs have a significant role in efficient filling and emptying of the LV and could be used to characterise cardiac performance.8 20 However, the assessment and interpretation of intraventricular pressure gradients in clinical practice remains complicated by its dependency on a large number of factors and interactions.10 21 Furthermore, flow occurs in multiple and rapidly changing directions, forming complex vortex patterns.10 20 The complexity of intraventricular flow and technical limitations of ultrasound imaging, the standard method in cardiovascular assessment, make it difficult to relate intraventricular flow patterns and derived IVPDs to LV myocardial function in a quantitative manner.10 20 21
The increasing availability of cardiovascular MRI has made it an advantageous alternative from a technical point of view due to its high image quality, reproducibility, repeatability, plane of view flexibility, sufficient spatial and temporal resolution and reduced operator dependency. Furthermore, MRI-based IVPD calculations allow for a more flexible definition and alignment of the operator’s ‘scan line’, which could be relevant when the blood flow exhibits a curved trajectory.17 Additionally, two-dimensional-velocity information from phase contrast MRI improves the accuracy of IVPDs even if the temporal resolution, a critical parameter to calculate IVPDs,22 is lower in comparison with ultrasound. In fact, Thompson and McVeigh13 reported that a minimum temporal resolution of 44 ms may avoid significant underestimation of the local acceleration contribution to the total intracardiac pressure differences. Previously, making use of computational fluid dynamics simulations, we assessed the impact of temporal resolution in IVPD calculations, showing that the temporal resolution of phase contrast MRI is, at least in theory, sufficient to resolve IVPDs. Furthermore, we also showed that IVPDs estimated by a one-dimensional method as colour-Doppler ultrasound are larger in magnitude than when the two-dimensional velocity information was used, but the estimates based on two-dimensional velocity information are more accurate, especially in extreme scan line misalignments,23 which could be particularly sensible after mid and late diastole due to formation of vortices.8 14 We speculate that this explains, at least partly, some of the difference between values reported here and in other studies.9 15–17
There were no significant differences in E-IVPD and A-IVPD between the groups. This may be a consequence of early filling pseudonormalisation due to greater filling pressures. Additionally, in HFpEF patients, pronounced diastolic abnormalities can often be elicited only during physiological perturbations, such as exercise or dobutamine infusions,24–26 as subjects with HFpEF exhaust their reserve to preserve the diastolic suction force at rest, limiting their ability for adaptation to stress.24 25 Nonetheless, our results demonstrate that HFpEF is associated with a greater magnitude of the ER-IVPD. Although, the slope of mitral inflow deceleration temporally coincides with ER-IVPD, it is interesting to note that we did not find significant differences in the deceleration time between the groups, and that ER-IVPD was not strongly related to the deceleration time. Therefore, our data suggests that ER-IVPD may be a more sensitive marker of diastolic function in HFpEF.
We also examined systolic IVPDs. A typical biphasic IVPD pattern was observed in systole, with a positive peak immediately followed by a negative one. HFrEF individuals exhibited lower values, whereas the HFpEF group presented an overall higher total magnitude of S-IVPD and SR-IVPD, suggesting differences in systolic flow dynamics between groups. These differences could be related to the unsteady nature of ejective flow, abnormalities in chamber geometry, and/or the sequence of regional contraction.20
Our reproducibility and repeatability assessments suggest a general adequate inter and intra-operator variability for early diastolic IVPD parameters. Reproducibility and repeatability were lower for A-IVPD, probably due to a more complex flow after mid and late diastole.8 14 Systolic parameters evidenced a need to refine the standardisation of the method, particularly for S-IVPD. The overall correlation between IVPD parameters and echocardiographic indexes was weak or non-existent. In fact, previous publications have pointed out a weak correlation between Doppler echocardiographic estimates of LV filling pressure with invasive filling pressure measurements and the necessity to include further analysis of non-invasive measures.27 28 In contrast, echocardiographic16 17 and MRI13 based IVPD parameters have shown good agreement against invasive intraventricular measurements, adding potentially relevant information for cardiovascular assessments.
The reported data should be interpreted considering the strengths and limitations of the study. Strengths of this study are the inclusion of patients with HFrEF and HFpEF, and the assessment of IVPDs with phase-contrast MRI, which overcomes a number of assumptions made with colour M-mode echocardiography and allows for a more consistent interrogation of intraventricular flow. Our study also has limitations. We did not perform invasive catheter-based measures of distensibility which would have been unfeasible in the absence of a clinical indication for LV catheterisation. From a technical point of view, the MRI acquisition requires relative long breath-holds (~20 s) and has limited temporal and through plane spatial resolution, while the processing could be affected by the image alignment and assumptions made about the nature of flow from the three chambers view. On computation of the IVPDs, viscous forces are neglected and it is assumed that inflow and outflow is laminar.9 17 25 On average, our HFpEF subjects did not have marked left atrial enlargement, suggesting the presence of mild HFpEF. This may have led to underestimations of true underlying differences. Our population was a clinical sample referred for a cardiac MRI study, which may not fully represent population-based trends. Moreover, complementary myocardial mechanic studies could be included to improve the analysis.29
In conclusion, we demonstrated the feasibility to assess IVPDs throughout the cardiac cycle using phase-contrast MRI and compared IVPDs between subjects without HF and subjects with HFrEF and HFpEF. Our findings suggest distinct patterns of diastolic IVPDs in HFpEF, implying differences in the nature of diastolic dysfunction between the HF subtypes. Further research is warranted to exploit MRI analysis thoroughly to assess the significance of these novel indices regarding risk stratification and response to therapy.