Indices of central aortic pressure waveform and ventricular function

The seminal studies by Hill [1,2] on energetics and thermodynamics of skeletal muscle laid the foundation for fundamental research into muscle physiology. His numerous and elegant experiments demonstrated the quintessential property of striated muscle – the dependence of muscle contraction on loading conditions [3,4]. As in these studies using isolated muscle preparations, characterization of contractility of cardiac muscle was also done with experiments on isolated bundles of cardiac (papillary) muscle. A similar dependency of muscle contraction on initial conditions of length and preload was found with cardiac muscle, as well as the dynamics of the imposed load on the contracting muscle, characterized with force–length and force–velocity relationships [5,6]. However, direct application of these principles to the noninvasive assessment of cardiac contractility is complex because of the three-dimensional structure and function of the heart compared with isolated single muscle bundles. The heart, as a pump, is governed by interrelated constitutive laws of biomechanics which determine the alterations of chamber dimensions through the contractile machinery of the sarcomeres [7,8]. In general clinical parlance, the load on the contracting ventricle, described as afterload, is considered to be the arterial pressure or, more specifically, the pressure during systole, when the aortic valve is open, and the pressure in the aorta is essentially similar to the intracavity pressure of the ejecting ventricle [9,10]. This implies that the pressure–volume relationships that are considered to characterize the contractile properties of the intact heart as a mechanical pump [11] also represent the force–length relationships that have been developed as the basis of the underlying mechanisms of force development in isolated muscle experiments [5,12]. However, the absolute magnitude of pressure during systole, although of importance, is not the only determinant of the loading conditions that affect the contractile properties of the myocardium. The timing of pressure changes during systole is also a significant factor for the operation of the intact heart as an efficient pump, which depends on both emptying of the ventricle because of contraction and adequate relaxation to provide sufficient filling, affecting the preload dependence on contractile performance within the limits of the Frank-Starling mechanism [13]. The importance of both magnitude and timing of changes in pressure during systole has been elegantly demonstrated in experiments in the intact circulation, wherein magnitude and timing are shown to have independent effects on diastolic relaxation [14]. Changes in systolic pressure were not because of changes in flow, but were imposed as additional secondary brief pressure augmentation with an external source – similar to the phenomenon seen as early or late-systolic augmentation because of wave refection [15]. Although aortic pressure during systole is a general description of ventricular afterload, this concept assumes that aortic flow is constant with changes in aortic pressure. However, a more comprehensive concept of afterload is considered to be aortic input impedance [16,17], which is characterized in the frequency domain as a ratio of harmonic components of aortic pressure and flow and expressed as the frequency spectrum of impedance modulus and phase [18]. The impedance concept has been used in the construction of models for experiments in isolated hearts [19] and shown to characterize afterload in the intact heart in comparison with force–length relationships of isolated muscle experiments [20]. Under steady-state conditions, aortic input impedance is determined only by the properties of the arterial vasculature, incorporating dimensional, mechanical and elastic properties of the arterial wall, and wave propagation phenomena described, in part, by pulse wave velocity (PWV) and wave reflection [18]. Indeed, the 1922 landmark article by Bramwell and Hill (the same AV Hill of muscle physiology) [21] suggests that PWV, a marker of stiffness of the vessel wall, can be considered as a suitable surrogate for afterload. This has also been shown in many more recent studies assessing the association of PWV and ventricular function [22,23]. Thus, consideration of basic haemodynamics suggests that ventricular–vascular coupling is affected by both steady and pulsatile phenomena, which determine the afterload to the contracting ventricle. The study by Cauwenberghs et al.[24] in this issue of the Journal of Hypertension describes an investigation that addresses the association between indices of cardiac and arterial function based on the basic physiology and haemodynamic principles of ventricular–vascular coupling. The study is conducted in 1233 adult individuals over a broad age range (second to ninth decades; mean age 48 years) with 41.5% of the group classed as hypertensive. Cardiac function is characterized by noninvasive echocardiography and Doppler techniques using tissue Doppler imaging. The flow Doppler and tissue Doppler imaging methodology allows computation of contractility indices using transmitral velocities (early, E, and late, A), mitral annulus velocities (systolic, s′; early, e′ and late, a′ diastolic velocities) and longitudinal (LS) and radial (RS) strains. Arterial indices were obtained from the central aortic pressure wave derived from the radial pulse using applanation tonometry and a transfer function algorithm. Systolic pressure augmentation was determined from the aortic waveform features as augmentation index (AIx), a parameter independent of calibration, and absolute augmented pressure. Central aortic pulse pressure (cPP) was obtained from the aortic waveform calibrated with values of brachial cuff pressure applied to the peripheral pulse. In addition to central aortic pressure, aortic stiffness was assessed from carotid–femoral pulse wave velocity (cfPWV). The significance of the findings of this study is that derived parameters (E/A ratio, E/e′ ratio, LS and RS) that quantify the contractile state of the myocardium are associated with indices of arterial function over an age range that shows the marked age-related change of the interaction between ventricular and arterial function. Generally, the findings confirm the expected associations between increased risk of left ventricular dysfunction and increased cfPWV, cPP and augmented pressure. As in other studies [25,26], AIx was found to change little after the fifth and sixth decades, whereas augmented pressure had a strong linear increase across the whole span. Hence, AIx was not sensitive to the age-related changes in ventricular–vascular coupling in the elderly. A second important finding of this study was the effect of age on the association between the interaction of cardiac and arterial indices. RS shows an increasing (positive) association with augmented pressure, cPP and cfPWV up to the sixth decade of age, after which it reverses (becoming negative). This suggests that the ageing heart is able to compensate for the increase in age-related afterload, as seen as increase in aortic input impedance with age [27], only up to the fifth and sixth decades by increasing myocardial strain to eject the required stroke volume against an increase in pressure. After this age, the heart decompensates, a hallmark for the initial changes that can lead to heart failure. The finding is of significance in that it is associated with a number of similar findings from many other independent studies. From the Framingham cohort it was found that although diastolic pressure is a predictor of cardiovascular risk before the fifth decade of age, it is pulse pressure that is predictive after this age [28,29]. This highlights the important role of arterial stiffness after the fifth and sixth decades in driving the increase in pulse pressure. What the study by Cauwenberghs et al.[24] contributes to this significant alteration of age-related predictors of cardiovascular risk is that the increase in pulse pressure is because of the secondary augmented component (augmented pressure), primarily because of the effects of increase in aortic stiffness and associated changes in PWV and wave reflection, and it is augmented pressure that is associated with cardiac indices of contractility. With increase in longevity of human populations, the age range at which the reversal of the association between cardiac and arterial indices, as found by Cauwenberghs et al.[24] (fifth and sixth decade), can be considered as ‘middle age’. In this age range, many of the arterial indices undergo an increase in rate of change with age [30] causing a disturbance and so increase the mismatch in ventricular–vascular coupling. Aortic PWV increases more rapidly with age and is associated with a more pronounced increase in pulse pressure with age and hypertension [31,32]. A significant change also occurs in the differences of arterial stiffness (as measured by PWV) between central and peripheral arteries. In large studies in which aortic and brachial PWV was measured at the same blood pressure, aortic PWV is lower than brachial PWV in youth, but increases at a much faster rate with age, so that after the fifth and sixth decades it is higher [31,33]. That is, a reversal of stiffness gradient occurs in the same age range as the reversal of the association between cardiac and arterial indices found by Cauwenberghs et al.[24]. There is not much evidence yet of how the arterial stiffness gradient can be used as a diagnostic marker, but some recent studies indicate that it may be a significant parameter associated with progression of kidney disease [34]. The findings of the study by Cauwenberghs et al.[24] provide insight into the potential haemodynamic factors that may predispose to age-related development of myocardial dysfunction leading to heart failure. Indeed, one of the primary motivations for the study was to uncover potential pathophysiological mechanisms that lead to subclinical or asymptomatic left ventricular dysfunction and propose indices that may be used to identify patients predisposed to higher cardiovascular risk. It has been demonstrated that this can be achieved by use of conventional echocardiographic and Doppler techniques and the noninvasive estimation of the central aortic pressure waveform from a calibrated peripheral pulse waveform. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.