EL in the E-filling period in the HCM and H-LVH groups
The ventricular remodeling processes associated with heart disease alter left ventricular (LV) hemodynamic parameters, including intraventricular vortex and energy loss. Intraventricular vortex can be described as fluid structures that have circular or swirling motions[12]. Meanwhile, energy loss (EL) is the frictional heat generated by viscosity blood. Although there was no difference in the degree of diastolic dysfunction between HCM and H-LVH cases evaluated by conventional parameters, the changes of left ventricular hemodynamics especially during the E-filling phase differed. During the E-filling phase, average EL was lower in the HCM group compared with the H-LVH group, which was associated with reduced LVEDVI and intraventricular velocity gradient from base to apex (Vbp) determined by multiple stepwise regression analysis. The diastolic intraventricular velocity gradient derived from VFM could be useful for estimating impaired LV relaxation and local flow dynamics in the ventricular chambers[13, 14]. Normally, there was a progressive intraventricular pressure difference that extends from the LA to the LV apex driving early diastolic filling, which is generated by rapid myocardial relaxation and recoil of elastic elements compressed during ejection [15]. Then, a strong vortex pair behind mitral valve leaflets appear was initiated. In this study, for patients with HCM, impaired relaxation and reduced intraventricular volume diminishes the ability of the LV to function as a suction pump, resulting in decreased Vbp [14], and the associated ring vortex at the mitral valve tips was reduced in size. Then, the weaker filling inflow jet would lead to decreased EL in the HCM group.
Although Vbp in the H-LVH group also tended to decrease, EL during the E-filling period was significantly increased in the H-LVH group. This is likely because different from the effect of LVEDVI on EL during the E-filling period in the HCM group, EL during the E-filling period is instead affected by LVMI in the H-LVH group. “Pathological” left ventricular hypertrophy (LVH) in HCM mainly has primary myocardial properties at the microscopic level, including myocyte disarray, interstitial fibrosis and replacement fibrosis, and “compensatory” LVH in hypertension is usually a compensatory mechanism in response to increased hemodynamic load, resulting in cardiomyocyte hypertrophy and extracellular matrix remodeling[6]. With increasing left ventricular weight, the oxygen demand increases, myocardial cell compensation increases, and microvascular dysfunction occurs, aggravating myocardial fibrosis and endothelial cell dysfunction[16]. The increased pressure load on the inner myocardium compared with the outer myocardium weakens longitudinal contraction. Previous studies have found that although left ventricular strain is reduced in both diseases, HCM patients have marked reductions in LS and CS, whereas H-LVH cases have less reduction in LS and unaffected CS[17]. Uncoordinated contraction of inner and outer myocardium would produce irregular blood flow, and heterogeneous flow field caused by the strong collision between high flow speed and wall shear flow inevitably increases blood energy consumption[18].
In addition, LV mass and LV hypertrophy in hypertension are strongly associated with impaired relaxation and increased LV filling pressure[19]. When left ventricular filling pressure is elevated, the flow of left atrial blood into the left ventricle is limited, and the impact of left ventricular inflow tract blood flow on the mitral valve is reduced[16], which impairs the formation of normal vortices, with increased number of vortices and ineffective vortices loaded in the LV apical part during E-filling even to the end of the atrial contraction period. Non-physiological vortex formation leads to increased blood flow dispersion and instability, causing inflow tract deflection and lateral force generation as well as higher energy consumption. From the above, we can infer that differences in abnormal diastolic hemodynamics observed between HCM and H-LVH are reflected by EL during the E-filling phase and are affected by different pathological cardiac configurations between HCM and H-LVH.
Non-physiological vortices in HCM and H-LVH
Vortex area in the HCM group was the smallest in each period, and in eight patients (32%) of the latter group, no well-formed E-filling vortex ring core was detected; LV interior volumes tended to decrease, although statistical significance was not reached. Previous studies have confirmed that LV shape and internal volume also play critical roles in vortex ring dynamics in the LV filling and ejection phases. Reduced LV volume could deprive the LV of its ability to enhance the formation of ring vortices at the mitral valve tips,[20] indicating the importance of LV morphology. Interestingly, we also found that Vbp was smaller and EL during the A-filling phase was increased in HCM patients without normal vortex formation. Under normal circumstances, blood flows towards the apex prior to the mitral valve opening, and the mitral annulus moves rapidly away after the valve opens; thus, the created intracardiac pressure gradient promotes vortex formation. Once generated, vortices as relatively longstanding inertial flow structures can create a virtual hydrodynamic channel extending from the mitral valve towards the apex of the heart, which facilitates filling by reducing convective losses and enhancing the function of the LV as a suction pump[21]. These findings suggest that intraventricular pressure gradient and the vortex promote each other. Once vortex generation is impaired, this mechanism could weaken or even disappear. This suggested that myocardial diastolic function appears to be more vulnerable in patients with HCM, in accordance with previous studies[4, 22].
The study demonstrated that the vortex additionally contributes to diastolic function by “pulling” blood from the LA into the LV, particularly during the E-wave deceleration, diastasis and late filling phases, which helps 10–15% of its filling volume enter the LV at no metabolic or pressure cost [23]. In most cases, its disappearance is unlikely to result in decreased cardiac output, because the heart can compensate for the disappeared vortex without affecting cardiac output. However, without changing the mechanical properties of the myocardium, this can only be achieved by increasing atrial thrust and/or accelerating diastolic speed, even increasing atrial pressure. In other words, the heart could fill the LV without normal vortex, but at the cost of increasing metabolic demand and/or atrial pressure[24].
EL during the A-filling and ejection phases
EL increased in the A-filling and ejection phases in both HCM and H-LVH groups, but vortex circulation values did not increase accordingly. Circulation is one of the main parameters reflecting vortex strength. EL increase is related to elevated vortex strength, which seems to be a normal physiological phenomenon or in a highly hemodynamic state. However, in the absence of vortex strength increase, elevated EL indicates a turbulence in the intraventricular region [7]. The generation of intraventricular turbulence during A-filling in HCM and H-LVH is related to left ventricular diastolic dysfunction manifested by significantly decreased mitral annulus velocity (e ') and elevated left ventricular filling pressure. Decreased left ventricular elastic recoil and relaxation force may cause left atrial contraction compensatory filling actively [25]. To maintain a certain filling pressure, blood flow into the left ventricle with the direction and speed change drastically, intraventricular flow velocity increases, coupled with elevated left ventricular stiffness, and the turbulence phenomenon aggravates such irregular blood flow and shear flow chamber wall; the intense collision inevitably increases the energy consumption of blood. In addition, increased EL-ave during the A-filling period of HCM is related to decreased LVEDVI. It may be caused by the confinement imposed by decreased LV volume on the filling vortex, which could inhibit the formation of vortex and affect its stability[26]. At this time, the vortex loses its original assisting effect and increases energy consumption.
Fibrosis of the left ventricular wall in HCM and H-LVH may lead to impaired contractile deformation ability of the left ventricular myocardium[27]. Therefore, extra work and enhanced energy consumption are required to maintain normal ejection. This reflects the inefficient hemodynamic status of HCM and H-LVH.
There were several limitations that should be pointed out. The main limitation is that the sample size of this study was limited, especially in the HCM group. As a result, LVEDVI in HCM patients with no well-formed E-filling vortex ring was decreased, but statistical significance was not reached. It is necessary to assess more patients with HCM to explore the anatomical factors of HCM patients of no well-formed E-peak vortex ring, e.g., abnormal papillary muscle position, thickening of ventricular wall position, etc. Secondly, in this investigation, we did not measure LV pressure by cardiac catheterization, and the examined patients only underwent the vector flow mapping test. Our data generated by vector flow mapping have not been compared with the invasive intraventricular pressure gradient. Future studies with larger patient cohorts are required to overcome these limitations and to validate our findings.