Function of the heart

Ventricular pump performance, or the proper blood supply to the tissues at adequate filling pressures, can be evaluated through function curves relating filling pressure to mechanical output estimations, such as stroke volume (SV, the volume ejected per beat), cardiac output (CO, the volume ejected per minute), stroke work (the product of mean ejection pressure and SV), among others. Such curves demonstrate the Frank-Starling mechanism of the heart, which states that the SV of the heart proportionally relates to the end-diastolic volume (EDV) [16]. EDV (preload) or surrogated quantities of volume, such as pulmonary capillary wedge and LV end-diastolic pressure (EDP) are used to generate the curves for describing the Frank-Starling mechanism (see figure 1.7). Shifts of the function curves are related to changes in intrinsic contractile performance, but effects caused by altered diastolic compliance cannot be differentiated from those caused by altered contractile performance [16], [17]. Contractile function is the intrinsic property of the cardiac muscle to contract independently of changes in loading conditions (preload, which is the load present at the end of diastole before the beginning of systolic contraction, or afterload, which is the systolic load on the LV after systolic contraction starts). Contractile function relates the rate of contraction with the peak force of the cardiac muscle and, often, with the rate of relaxation (the lusitropic effect) [16], [17].

Although both aspects of heart performance, systolic (myocardial con-traction) and diastolic (relaxation and filling) function, overlap and interact, in practice, it is convenient to analyse them separately [16].

Systolic function

Myocardial contraction or systole can be defined as the period between the isovolumic contraction and the end of the ejection phase. The SV is the volume of blood pumped from the heart during ejection and the CO is calculated by multiplying SV and HR [16].

According to the Frank-Starling mechanism or Starling’s law of the heart, the initial muscle fibre length regulates the contraction force (at any given tension). Based on this premise, experiments introduced the concepts of preload, afterload and contractility as mechanical determinants of cardiac function [17].

Preload can be defined as ventricular end-diastolic wall stress, which is re-lated to muscle sarcomere length and venous filling pressure. Corresponding to Starling’s law, SV and wall shortening extent and velocity are proportional to preload, while systolic wall stress and SV present an inverse relation at a constant preload. Alterations in preload are a crucial factor of ventricular performance and length-function curves. Indeed, the capacity to increase preload in stress situations is a functional reserve to maintain LV systolic performance in many disease states [16], [17].

Afterload, a major determinant of SV, is characterised as the tension (force or wall stress) on the LV fibres after shortening starts, which is basically the arterial pressure. With a constant preload, a rise in LV ejection impedance induces a fibre shortening and an LV SV decline. In a healthy heart, SV can be preserved by augmenting LV EDV and EDP, i.e., an afterload increase is met by a preload increase. In contrast, the diseased heart (such as in heart

Figure 1.7: Frank-Starling curves.The Frank-Starling law characterises the correla-tion between the contraccorrela-tion force and the initial length of muscle cells. The failing heart curve shows a decreased slope indicating that higher cardiac preload is required to maintain adequate stroke volume, i.e., contractile force. Adapted from the refer-ence: Optimal perioperative fluid management: What is the strategy? - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Frank-Starling-curves-of-ventricular-contractility_fig2_306088064 [accessed 20 Oct, 2019]

via license: Creative Commons Attribution 4.0 International [27].

failure) or the intact heart during acute conditions (such as hypovolemia) has limited preload reserve and, thus, cannot increase sufficiently to maintain the SV [16], [17].

Contractility is the generic term to express the intrinsic strength of myocardial contraction, and thus it has been related to the inotropic state, although it has not a straightforward quantitative definition. With constant preload and afterload (loading conditions), cardiac performance is related to contractility, which in turn is affected by different factors as sympathetic neural activity. Responses of the LV contraction to alterations in preload, af-terload, and contractility are assessed through the analysis of the LV pressure-volume relationship (functional curves) [16], [17].

Physiologic measurements of LV systolic function

LV ejection fraction (EF) is the most well-accepted expression of global LV function, indicating how much EDV is ejected from the LV with each contraction. Various imaging approaches are used to measure EF, being echocardiography the standard (see Chapter 2). Accuracy depends on the limitations of the method and, therefore, magnetic resonance imaging (MRI) has been proposed as a quality alternative to improve EF estimation (see Chapter 2) [17]. For the EF calculation, LV EDV and end-systolic volume (ESV) are obtained, and the following equation is applied:

LV E jec t ion Frac t ion(E F) = (LV E DV −LV E SV)

LV E DV = SV

E DV

(1.1) Maximal ventricular elastance is another common parameter to assess systolic function. End-systolic pressure-volume intercepts form a straight line on the pressure-volume curve for a given degree of contractility, and the slope of this line is the maximal elastance (see figure 1.8), which is directly proportional to contractility. This approach involves the development of pressure-volume curves and the control of either preload or afterload [17].

Diastolic function

Diastolic function is the filling capacity of the heart to reach an adequate EDV at appropriate blood pressures.

Determinants of LV diastolic performance vary in their importance and interaction during the four diastolic phases, which are isovolumic relaxation,

Figure 1.8: Estimation of the maximum elastance.Three differently loaded cardiac cycles. The systolic pressure–volume points all lie on a line termed the end-systolic pressure–volume relationship (ESPVR). The slope of the ESPVR is maximum elastance (Emax). At any time during systolic contraction (e.g., 50mstime points are shown as filled circles) a line can be drawn connecting pressure–volume points from each of the differently loaded contractions defining elastance (∆P/∆V) at that time point. Ventricular systolic contraction can therefore be regarded as a time-varying elastance. Adapted from the reference: Left ventricular function: Time-varying elast-ance and left ventricular aortic coupling - Scientific Figure on ResearchGate. Avail-able from: https://www.researchgate.net/figure/Three-differently-loaded-cardiac-cycles-The-end-systolic-pressure-volume-points-all-lie_fig1_307959220 [accessed 20 Oct, 2019] via license: Creative Commons Attribution 4.0 International [28].

early LV filling, diastasis, and filling at atrial contraction. This division is only a convention to facilitate the description of LV diastolic properties since it has been difficult to understand LV diastolic function due to: 1) the complex interaction between factors through all phases (particularly in disease states), 2) the additional factors that influence LV diastolic properties, such as systolic function, pericardial restraint, among others, and 3) the overlap of the effects of these factors on the different phases of diastole [16], [17].

LV diastolic properties

During systole, the compression of elastic cardiac components produces elastic recoil, which in turn results in an LV suction effect by active relaxation during the early filling phase. This effect increases the pressure gradient between LA and LV, thus enhancing early diastolic filling and producing a

normal LV filling pattern. Abnormalities in relaxation generate lower trans-mitral gradients and an anomalous LV filling pattern with greater proportion of filling at atrial contraction. Under stress conditions, such as exercising, this pattern hampers the ability of the heart for an optimal filling [16], [17].

The−d P/d t_maxcurve andτ(the time constant of relaxation) are calculated invasively as estimations of the rate of isovolumic relaxation. These methods present several limitations that restrict its application, hence other indices of isovolumic relaxation has been proposed using echocardiography and tissue Doppler measurements (see Chapter 2). Nonetheless, the best method to assess LV relaxation is still under research [16], [17].

Myocyte/myocardial and LV chamber compliance are less energy-dependent properties that govern the LV filling after relaxation. The former is determined by collagen fibres and sarcomeric proteins while the latter is determined by external elements, e.g., the pericardium and pulmonary airway pressure. Stress-strain relationship curves are used to evaluate myocardial compliance, yet in vivo measurements are impractical, so pressure-volume loops are determined during diastasis to characterise the combined effects of myocardial and chamber compliance and external forces, such as LV relaxation and viscoelastic properties. Chamber compliance, or its reciprocal (stiffness), is assessed with the slope of a tangent to the pressure-volume relationship, in which a steeper slope indicates a stiffer LV (see figure 1.8). However, this approach has several restraints, and its application has limited to experimental studies [17].

LV relaxation and chamber compliance are critical determinants of trans-mitral pressure gradient and LV filling. During diastole, the transtrans-mitral pressure gradient ensures competent LV filling whereas normal SV is pre-served by an adequate LV EDP such that the myocardium volume is optimal (Frank-Starling mechanism). Changes in ventricular stiffness induce ad-justments in LV EDPs to maintain filling. A slower LV relaxation causes a reduction of early diastolic transmitral gradient and a greater proportion of filling at atrial contraction. A compensatory increase of atrial pressure might be present in either case. At young age, diastole shows an efficient early filling whilst, in the aging heart, a slower LV relaxation produces a higher filling at atrial contraction. During exercise, a healthy heart shows a faster LV relaxation rate and a shorter PR interval, reducing diastolic filling time to preserve both early and late filling without raising atrial pressure [16], [17].

Non-invasive evaluation of LV diastolic function

For practical reasons, non-invasive methods for calculating LV filling patterns have been developed to assess indirectly LV diastolic function. The current

gold standard technique is echo-Doppler, and age-related values has been established for transmitral flow velocities (Chapter 2). The assessment of dias-tolic function is complemented with the calculation of additional parameters, such as maximal LA volume, LV filling in response to preload reduction (the Valsalva manoeuvre) and mitral annular motion assessed by tissue Doppler imaging (TDI) (see Chapter 2).