Increased arterial stiffness is a well recognized marker of cardiovascular risk in several epidemiological settings [1–3]. Different conditions affect arterial stiffness, the most prevalent of which are hypertension, diabetes and atherosclerosis . The pathophysiological consequences of increased arterial stiffness impact not only the vessel function and the relative hemodynamics but also the left ventricle (LV), due to the strong interaction between ventricular and vascular load . LV counterbalances the increased hemodynamic load, due to the great central pulsatility, mainly through an increased energy expenditure to eject the blood, with development of compensatory LV hypertrophy and geometric adaptation .
In a number of population-based studies, central pulse pressure (PP) is demonstrated to be superior than peripheral PP in the prediction of target organ damage and cardiovascular events . Although a system of branching tubes, such as the arterial system, has theoretically a high internal damping to absorb the wave propagation coming from the heart, the different structural configuration of arteries (elastic and/or muscular) makes a reflexed wave significant to explain hemodynamic load, as reflection occurs when a change in the characteristic impedance of the tube system occurs . We can speculate that this phenomenon rises at the transition between elastic (conduit) arteries and the beginning of resistance arteries.
The velocity of the reflexed wave is an inverse function of elasticity. In a condition of good arterial elasticity, the reflexed wave is quite slow and reaches the aortic valve during LV pressure decay, a typical pattern met in young persons. When arterial stiffness increases, the velocity of the reflexed wave increases and does not anymore intercept LV ejecting pressure decay, whereas overlapping with the peak-ejection pressure, at the time of maximal myocardial contraction, a time recognizable as the inflection point on the ascending phase of the pressure waveform (Fig. 1). The augmentation index is, therefore, a measure of the contribution that wave reflection makes to the peak central pressure and is an indirect measure of the central wave reflection. Previous studies have demonstrated the augmentation index is an important prognostic marker in hypertensive heart disease and heart failure . When the inflection point is recognized, it is possible to decompose the pressure waveform in a forward (incident) and backward (reflected) phase to calculate the augmentation index (Fig. 1).
From the aortic pressure waveform, under specific geometric assumptions, Westerhof et al. could quantitatively estimate the forward and backward pressure components forming the pressure waveform, using a commercial instrument. They made a pulsed ‘wave separation analysis’ (WSA) and derived an index to quantify the magnitude of reflection, called reflection magnitude. The advantage of reflection magnitude over the augmentation index is that it is independent of the time of return of the reflected wave and can be therefore calculated in any circumstances and not only when the reflexed waves cross the peak LV pressure.
However, under the assumption that the WSA may really dissect efficaciously the composite central pressure waveform, and beyond the undeniable gain of pathophysiologic information, what is the impact of this analysis on daily practice, especially when compared with the information gained by the simple measure of systolic, diastolic, PP and, when available, augmentation index? To provide initial answers to this question, Cauwenberghs et al. evaluated feasibility and usefulness of WSA in a population sample across a wide range of age, comparing with LV geometry and function. The study, which is published in this issue of the Journal, involved 616 patients from the FLEMENGHO study, who underwent echocardiography and pulse wave-form analysis with SphygmoCor apparatus (AtCor Medical Ltd, Sydney, Australia) from which the WSA algorithm derived forward pressure and backward pressure. The authors report that age significantly affect the relationship between backward pressure and forward pressure with an increased reflection magnitude, consistent with previous studies and as already demonstrated for augmentation index .
However, failure of the method to measure WSA occurred just in those patients who were at higher risk of heart failure with preserved ejection fraction (HFpEF), old hypertensive women, with isolated systolic hypertension [8,12]. In those patients, understanding the hemodynamics could be important, and thus, failure of the WSA method represents a major limitation. In addition, in conditions in which contractility is near normal, such as is probably occurring in this population sample, there is no clear demonstration that the reflection magnitude does better than the augmentation index. On the other hand, when length/velocity relation is substantially abnormal, the forward wave can be still rising when the backward wave is already coming down  and a measure of forward pressure, backward pressure and reflection magnitude might be elucidating. Eventually, it is unclear whether assessment of reflection magnitude adds to the calculation of augmentation index, when reflected waves reach ascending aorta during LV pressure climb . In practical terms, and focusing to clinical practice, the dissection of the pressure waveform in the two components, forward pressure and backward pressure, does not seem to have any adjunctive value compared with the knowledge of central (and perhaps even peripheral) PP.
However, from a theoretical point of view, decomposition of the pressure waveform into forward pressure and backward pressure opens stimulating questions regarding the impact of the single forward and backward components, relatively to the alteration of ventricular–vascular interaction [13–15].
The relations between LV systolic function and either central pulse pressure or the two waveform components (both components of afterload) are likely dominated by the LV geometric adaptation to the hemodynamic load , but the relation with diastolic function is much more complex.
Consistent with the relation found with central pulse pressure, both wave components (forward pressure and backward pressure) correlated with a number of markers of diastolic function . However, the meaning of the two components of the pressure waveform on the different parameters of LV diastolic function is difficult to reconcile considering the complex relation that the timing of pressure development and decay have with active LV relaxation, that is the portion of diastole that we may better estimate (whereas passive myocardial compliance is much more difficult to estimate). As demonstrated in pivotal experimental studies, imposing hemodynamic load during contraction (which roughly corresponds to the forward pressure phase) results in a prolongation of the contraction phase and a more rapid pressure fall , especially when end-systolic volume is small and favors restoring forces (i.e. when chamber contractility is high) [18,19]. This type of load is called ‘contraction load’ and roughly corresponds to the wall stress measured at the time between the inflection point and the peak of the pressure waveform, before the beginning of relaxation.
In contrast to what commonly assumed, active LV relaxation begins at the climax of the contractile force curve. This very earliest phase of relaxation, starting during end-ejection phase, was proposed to be named ‘auxobaric relaxation period’ and ends at the beginning of the isovolumic relaxation period  (Fig. 1). The hemodynamic load applied during early relaxation has an effect that is opposite to that of the contraction load, that is tends to anticipate LV pressure fall but delays LV active relaxation . Of course, the backward pressure is the waveform component that can be identified as the relaxation load. As expected, and consistent with the above pathophysiologic rationale, in the Cauwenberghs et al.'s study , whereas a higher forward pressure is positively related to faster LV relaxation (i.e. greater transmitral E/A ratio), the reflection magnitude, which represents the real relaxation load adjusted by the forward component, is associated with slower relaxation (i.e. lower E/A ratio). Also interesting is the observation that both waveform components are positively related to the E/e′ ratio that is used as a surrogate of LV filling pressure at the beginning of the passive LV chamber distension.
Recent data suggest the need for a refocusing of the impact of arterial stiffness on the LV as a potential causative factor leading to HFpEF . The study by Cauwenberghs et al. contributes to the awareness that the ventricular–vascular coupling needs to be examined across the entire cardiac cycle, rather than as a pure end-ejection phenomenon. It is worth to remember that an easy method to assess increased arterial stiffness, that is PP/stroke index ratio (PP/SVi), presents the same rationale of analyzing ventricular–vascular interaction across the entire cardiac cycle. The PP/SVi ratio has been indeed demonstrated to be particularly useful for the prediction of incident heart failure . Verification of the effect of pressure waveform decomposition on incident heart failure would be extremely interesting.
Conflicts of interest
There are no conflicts of interest.
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