Which blood pressure measurement reflects the phase when the heart relaxes and is always lower than the other measurement?

3.1.2 The cardiac cycle and electrical activation

The cardiac cycle is a series of electrical and mechanical events that occur during the phases of heart relaxation (diastole) and contraction (systole). The ventricular diastolic stage involves blood flow from the atria to the ventricles, and the ventricular systole includes blood flow from the ventricles to the pulmonary artery and the aorta. Cardiac systole is the myocardial cells’ mechanical response to an electrochemical stimulus originating from the sinoatrial (SA) node. By acting as a pacemaker it controls the cardiac cycle. The electrical activity originating from the SA node propagates through the heart’s fibrous skeleton (first the atrial mass, then the AV node) and the subsequent depolarization wave from top to bottom of the heart triggers the mechanical activation (cf. Refs. [2, 3]). The conduction of the electrical activity through the fibrous skeleton can be seen on an electrocardiogram (ECG), as shown in Fig. 3.3.

During each heartbeat, the ECG recording represents the electrophysiological activity and is obtained using electrodes mounted on the skin. In the same figure the conduction at the atria is shown as the P-wave and the PR interval corresponding to the delay in the AV node follows. The propagation of electrical activity across the ventricular myocardium creates the QRS complex, and the T-wave is known as ventricular repolarization (relaxation of the muscles). In imaging devices, the ECG signal is often widely used as a gating signal to capture heart images at different phases of the heart cycle.

4.1.2 The Cardiac Cycle

The cardiac cycle describes the sequence of electrical and mechanical events that occurs with every heartbeat. The normal duration of a cardiac cycle for a heart rate of 75 beats/minutes is 0.8 seconds [3],

(4.1)Duration of cardiac cycle(seconds/beats)=60(seconds/minutes)Heart rate(beats/minutes)

The cardiac cycle may be divided into phases in any number of methods, for instance four phases [1,3] or seven phases [2]. In the four phases method, the opening and closing of the heart valves explains this method of the cardiac cycle. These phases are [1,3]:

Phase I: Filling period—the inlet valve is opened to fill the ventricle and the outlet valve is closed. The volume of blood in the ventricle increases from about 45 mL (from previous cycle) to about 115 mL.

Phase II: Period of isovolumetric contraction—both valves are closed, blood volume is constant but the blood pressure increases to about 80 mmHg.

Phase III: Period of ejection—the outlet valve of the ventricle is opened and the inlet is closed and due to more contraction, the blood pressure rises.

Phase IV: Period of isovolumetric relaxation—both valves are closed and intraventricular pressure decreases without any blood volume changes.

The period of relaxation is called diastole in which the ventricle fills with blood and the period of ventricle contraction is called systole. Fig. 4.4 shows the cardiac cycle events for the left pump of the heart for two complete cycles. This figure illustrates the pressure–volume of the events. The top three curves illustrate the pressure changes in the left pump of heart including the aorta, left ventricle and left atrium. The fourth curve from the top denotes the volume changes in the left ventricle, the fifth one is electrocardiogram curve and the sixth curve denotes phonocardiogram (PCG; heart sound).

Electrocardiogram (ECG) of cardiac cycle: The ECG is a general clinical device used to measure the electrical activity of the heart. This device records the small extracellular signals which are produced by the movement of cardiac action potential through the transmembrane ion channels in the myocytes. This cardiac potential can be measured by microelectrodes. Scientific experiments have proved that a membrane potential is about −90 mV for a resting ventricular myocyte. The ECG is recorded by an arrangement of electrodes at precise locations on the body surface. The electrodes are located on each leg and arm, and six electrodes are located on the chest to obtain a standard ECG. Fig. 4.5 shows a standard ECG and its waves (P, QRS and T). Repeating waves denote the sequence of depolarization and repolarization of the atrium and ventricles.

Depolarization of the left and right atrium muscle is reflected by the P wave and during this event the atrioventricular (AV) valve is open and ventricle will be filled with blood. The QRS denotes depolarization of ventricular muscle and it appears 0.16 seconds after the P wave, during this event, due to ventricle contraction, the ventricular pressure rises rapidly. The T wave reflects depolarization of both ventricles and they begin to relax [3,4], see Fig. 4.4.

Normally, ECGs are recorded on paper with a vertical calibration of 1 mV/cm and a speed of 25 mm/seconds. In a normal record of ECG, a QRS follows each P wave. The shape of the ECG shows the heart function and it can reveal some heart problems, such as [2]:

atrial flutter,

atrial fibrillation,

first-degree AV block,

second-degree AV block,

third-degree AV block,

premature ventricular complex,

ventricular tachycardia and

ventricular fibrillation.

In the atrial pressure graph of Fig. 4.4, there are three minor pressure rises, a, c and v. The a wave occurs because of atrial contraction, the c wave occurs when the ventricles begin to contract, and the v wave occurs near to the end of ventricle contraction [1].

PCG of cardiac cycle: The opening and closing of the heart valves during the cardiac cycle produces sounds and these sounds are recorded by a phonocardiograph. There are two major sounds (S1 and S2) and two other sounds (S3 and S4). The sound of S1 (sound of “lub”) is for the closure of the AV valves (mitral and tricuspid valves), S2 (sound of “dub”) is for the aortic and pulmonary valves, S3 is a normal sound for children but for adults it is considered as a problem due to ventricular dilation and S4 is abnormal sound during atrium contraction due to changes in ventricle tissues. See Fig. 4.4 for the location of these sounds in cardiac cycle.

The frequency range of heart sound is between 10 and 500 Hz with low intensity [5]. Heart murmurs are abnormal heart sounds and they are produced because of turbulent flow of blood in the heart. Only a few heart problems produce abnormal noise, such as:

regurgitation or back flow due to heart valve problems (mitral or aortic valves);

stenosis or abnormal narrowing in mitral or aortic valves and

other murmurs, such as patent ductus arteriosus, the ductus arteriosus fails to close in infants after birth.

1.1.2 The Cardiac Cycle

The cardiac cycle includes two phases: diastole and systole (Fig. 1.4). In the diastole phase, blood returns to the heart from the superior and interior vena cava and flows into the right atrium. The pressure in the right atrium increases as blood flows into it. When the pressure of the right atrium exceeds the pressure of the right ventricle, the tricuspid valve opens passively allowing blood to flow into the right ventricle. At the same time, the oxygenated blood returning from the lungs flows into the left atrium. As left atrial pressure increases, the mitral valve opens and blood flows into the left ventricle.

In the systole phase, blood is forced to flow from the two atria into their respective ventricles as the atrial muscles contract due to the depolarization of the atria. There is a period called isovolumetric contraction during which the ventricles contract but the pulmonary and aortic valves are closed as the ventricles do not have enough force to open them. The atrioventricular valves also remain closed during the isovolumetric contraction period. The semilunar valves open when the ventricular muscle contracts and generates blood pressure within the ventricle higher than within the arterial tree. When the heart muscle relaxes the diastole phase begins again.

5.3 The cardiac cycle

The cardiac cycle describes all of the events that occur during one heartbeat and during the latent time until the next heartbeat. It makes the most sense to describe these events starting from the initiation of an action potential within the SA node (see Section 5.2). The cardiac cycle consists of two phases: diastole and systole. Cardiac myocytes do not contract during diastole, and this is when the majority of blood fills the heart chambers. During systole, the myocytes contract and eject blood from the particular chamber either into other heart chambers or into the vascular system. This textbook and many other resources use the terms systole and diastole interchangeably with ventricular systole and ventricular diastole. The contraction cycle of the atria can be described by their own systolic and diastolic pattern, however, the ventricular cycle is much more significant for the functionality of the heart and is typically the one referenced during normal discussion.

To depict the cardiac cycle, the aortic pressure, the left ventricular pressure, the left atrial pressure, the left ventricular volume, and the ECG are overlaid onto one figure that is plotted against time (Fig. 5.10; a similar figure can be drawn for the right side of the heart, with pressure values that are approximately one-sixth of the value compared with the left side of the heart). Recall that the ECG P wave is associated with atrial depolarization. During this time, the mitral valve is open and the left atrium forces the remaining blood into the left ventricle, effectively priming the left ventricles for contraction. This priming action occurs because during much of left ventricular diastole (and left atrial diastole), the left atrial pressure is higher than the left ventricular pressure, which suggests that the mitral valve is open. Any blood that enters the left atria from the venous pulmonary circulation passes directly into the left ventricles. Hence, one can observe a steady rise in ventricular volume during the diastolic portion of the cardiac cycle. During atrial systole, 10 to 20 mL of blood is forced into the ventricles, which acts to expand the ventricular muscle mass. This expansion causes an initial elastic recoil response, in addition to the ventricle muscle contraction, to aid in moving blood through the cardiovascular system. Note again that although we are discussing the left side of the heart, the same pattern is observed on the right side of heart (e.g., during ventricular diastole, blood passes from the right atria directly into the right ventricles).

Upon the onset of the QRS complex, there is a rapid increase in ventricular pressure because of ventricle contraction. This is associated with the closing of the mitral valve and isovolumic contraction of the ventricle. The left ventricle contracts for a short amount of time without losing volume because both the mitral valve and the aortic valve are closed and we assume that the compressibility of blood is negligible. As the QRS complex ends, the aortic valve opens (as a result of the left ventricle pressure surpassing the aortic pressure) and the left ventricle ejects blood into the systemic circulation. The duration of ventricle contraction is termed systole. The volume of blood in the ventricles reduces from approximately 120 mL to approximately 45 mL, which is termed the residual ventricular volume or end-systolic volume. The difference between the end-diastolic volume and the end-systolic volume is referred to as the stroke volume. During systole, the T wave is recorded, and this is when the ventricles begin to relax. At this time, the vascular pressure (e.g., aortic) is still lower than the ventricular pressure, so that blood continues to be ejected out of the heart for a few milliseconds. Toward the end of the T wave, the aortic valve closes (because the left ventricular pressure drops below the aortic pressure) and the ventricle enters the isovolumic relaxation phase, which marks the beginning of ventricular diastole. After a few milliseconds, the pressure in the ventricles returns to approximately 1 mmHg and the mitral valve opens again. At this point, diastole continues until the ventricles begin to contract and the mitral valve closes once again. As mentioned earlier, during the entire period of diastole, even though the left atrium is not contracting, the left ventricle is filling with blood. In fact, approximately 75% of the blood that enters the atrium passes directly into the ventricle without the aid of atrial contraction. During atrial contraction, the remaining blood volume enters the ventricles. Note that the discussion was for the left side of the heart, which is shown in Fig. 5.10. A similar discussion for the right side of the heart could be conducted, but the pressure would be reduced compared with the left side of the heart and the volumes are subtly different, although the stroke volume is largely the same.

The pressure in the atria remains fairly constant (and low) during the entire cardiac cycle. However, three major changes occur within the atrial pressure waveform, and they are denoted as the a (atrial contraction), c (ventricular contraction), and v (venous filling) waves. The a wave is associated with atrial contraction and occurs immediately after the P wave of the ECG. During the a wave, both atria experience an increase in pressure of about 6 to 7 mmHg, with the left atrium experiencing a slightly higher pressure increase than the right atrium. The c wave corresponds to the beginning of ventricular contraction and occurs immediately after the QRS complex of the ECG. This is caused primarily by the increased ventricular pressure acting on the AV valves. In addition, at the beginning of systole, there is a small amount of blood backflow into the atria because the valves have not yet fully closed. Combined, these two changes induce an increase in atrial pressure. The v wave represents a steady increase in atrial pressure that occurs during ventricular contraction, which is caused by venous blood from the systemic or pulmonary circuits entering the atria. When the AV valves reopen, this increased pressure aids in blood movement directly into the ventricles without atrial contraction.

Fig. 5.10 depicts the cardiac cycle for the left ventricle, left atrium, and aorta. The aortic pressure curve is what is estimated when a patient has his or her blood pressure taken, or more accurately, the maximum aortic pressure and the pressure at which the aortic valve opens. At the point that the aortic valve opens, the pressure in the aorta increases because of blood being forced into the vascular system from the left ventricle. At peak systole, the blood pressure in the aorta reaches approximately 120 mmHg under normal healthy human adult conditions. At the point that the aortic valve closes, the pressure in the aorta is approximately 100 mmHg. At the time of valve closure, the pressure increases by approximately 5 to 10 mmHg as a result of aortic elastic recoil and blood passing from the apex of the aortic arch back toward to the aortic valve. The backflow of blood occurs because the left ventricular pressure has dropped below the aortic pressure, and then the pressure gradient favors blood moving down the aortic arch toward both the abdominal aorta and the aortic valve (e.g., the different sides of the arch). The slight rise in the aortic pressure is termed the dicrotic notch. The following rise in aortic pressure is referred to as the dicrotic wave. Then, as a result of the viscoelastic recoil of the aorta, there is a slow, but continual, decrease in aortic pressure during diastole. At the end of diastole and the isovolumic contraction phase, the aortic pressure is approximately 80 mmHg. Once the left ventricular pressure surpasses this, the aortic valve opens and the pressure increases again to approximately 120 mmHg.

An additional interesting point is the sound that the heart makes during the cardiac cycle. A physician can listen to these sounds with a stethoscope. These sounds are caused by first the closure of the AV valves and then the closure of the semilunar valves. The sounds are generated by the valve vibrations during the closing process. As mentioned previously, the AV valves can bulge into the atrium and the semilunar valves can bulge into the ventricles immediately after closure. This is caused by an increase and a reversal in the pressure gradient across the leaflets. With respect to the AV valves, the papillary muscles and the tendons that attach to the valves (the chordate tendineae) experience recoil, inducing valve leaflet vibration. The semilunar valves are highly elastic and experience recoil because of the pressure difference. This elastic recoil generates an audible sound.

As we know, the heart beats approximately 72 beats per minute for an average human. Comparing between other animals, one can see that heart rate is inversely proportional to body mass (Fig. 5.11). Many models can be used to describe this relationship, some of which account for if the animal is warm-blooded or cold-blooded, what the daytime activity of the animal is, and how the animal developed from an evolutionary standpoint. For this textbook, it is important to keep in mind that, in general, animals with a lower mass will have a higher heart rate compared with animals with a larger mass.

The Cardiac Cycle

The cardiac cycle describes pressure, volume, and flow phenomena in the ventricles as a function of time. This cycle is similar for both the left and right ventricles, although there are differences in timing, which stem from differences in the depolarization sequence and the levels of pressure in the pulmonary and systemic circulations. For simplicity, the cardiac cycle for the left heart during one beat has been described (Figure 10).

The QRS complex on the surface ECG represents ventricular depolarization. Contraction (systole) begins after an approximately 50 ms delay and results in closure of the mitral valve. The left ventricle contracts isovolumetrically until the ventricular pressure exceeds the systemic pressure, which opens the aortic valve and results in ventricular ejection. Bulging of the mitral valve into the left atrium during isovolumetric contraction causes a slight increase in left atrial pressure (c wave). Shortly after ejection begins, the active state of ventricular myocardium declines and ventricular pressure begins to decrease. Left atrial pressure rises during ventricular systole (v wave) as blood returns to the left atrium by means of the pulmonary veins. The aortic valve closes when left ventricular pressure falls below aortic pressure, and momentum briefly maintains forward flow despite greater aortic than left ventricular pressure. Ventricular pressure then declines exponentially during isovolumetric relaxation, when both the aortic and mitral valves are closed. This begins the ventricular diastole. When ventricular pressure declines below left atrial pressure, the mitral valve opens and ventricular filling begins. Initially, ventricular filling is very rapid because of the relatively large pressure gradient between the atrium and ventricle. Ventricular pressure continues to decrease after mitral valve opening because of continued ventricular relaxation; its subsequent increase (and the decrease in atrial pressure) slows ventricular filling. Especially at low end-systolic volumes, early rapid ventricular filling can be facilitated by ventricular suction produced by elastic recoil. Ventricular filling slows during diastasis, when atrial and ventricular pressures and volumes increase vary gradually. Atrial depolarization is followed by atrial contraction, increased atrial pressure (a wave), and a second, late rapid-filling phase. A subsequent ventricular depolarization completes the cycle.

Valve closure and rapid-filling phases are audible with a stethoscope placed on the chest and can be recorded phonocardiographically after electronic amplification. The first heart sound, resulting from cardiohemic vibrations with closure of the AV (mitral, tricuspid) valves, heralds ventricular systole. The second heart sound, shorter and composed of higher frequencies than the first, is associated with closure of the semilunar valves (aortic and pulmonic) at the end of ventricular ejection. Third and fourth heart sounds are low-frequency vibrations caused by early rapid filling and late diastolic atrial contractile filling, respectively. These sounds can be heard in normal children, but in adults they usually indicate disease.

An alternative time-independent representation of the cardiac cycle is obtained by plotting instantaneous ventricular pressure and volume (Figure 11). During ventricular filling, pressure and volume increase nonlinearly (phase I). The instantaneous slope of the pressure–volume (P-V) curve during filling (dP/dV) is diastolic stiffness, and its inverse (dV/dP) is compliance. Thus, as chamber volume increases, the ventricle becomes stiffer. In a normal ventricle, operative compliance is high, because the ventricle operates on the flat portion of its diastolic P-V curve. During isovolumetric contraction (phase II) pressure increases and volume remains constant. During ejection (phase III) pressure rises and falls until the minimum ventricular size is attained. The maximum ratio of pressure to volume (maximal active chamber stiffness or elastance) usually occurs at the end of ejection. Isovolumetric relaxation follows (phase IV), and when left ventricular pressure falls below left atrial pressure, ventricular filling begins. Thus, end-diastole is at the lower right-hand corner of the loop, and end systole is at the upper left corner of the loop. Left ventricular P-V diagrams can illustrate the effects of changing preload, afterload, and inotropic state in the intact ventricle (see the following).

A P-V loop can also be described for atrial events (Hoit et al., 1994). During ventricular ejection, descent of the ventricular base lowers atrial pressure and thus assists in atrial filling. Filling of the atria from the veins results in a v wave on the atrial and venous pressure tracing. When the mitral and tricuspid valves open, blood stored in the atria empties into the ventricles. Atrial contraction denoted by an a wave on the atrial pressure tracing actively assists ventricular filling. The resultant atrial P-V diagram has a figure-of-eight configuration with a clockwise V loop, representing passive filling and emptying of the atria and a counterclockwise A loop, representing active atrial contraction. Thus, the atria function as a reservoir and conduit for venous flow (during ventricular systole and diastole, respectively), and as a booster pump for ventricular filling late in diastole.

20.7.3 Heart Valve–Blood Interaction

During the cardiac cycle, heart valves open and close due to their interaction with blood. The most accurate way to account for it is FSI modelling. However, the latter is even more challenging than ventricle FSI modelling, due to the abrupt nature of valve transient closure and opening. It is also due to leaflets’ coaptation, which implies the use of very fine fluid meshes and of small time steps in the numerical solution of the problem, thus leading to excessive computational expense. As a result, FSI modelling is commonly adopted only in idealized models characterized by simple geometries and nonphysiological parameter ranges (e.g., blood bulk modulus and Reynolds number), although Chandran and Vigmostad lately proposed the preliminary results of their in-home FSI algorithm allowing for patient-specific simulations with physiologic Reynolds numbers, realistic material properties, and highly resolved grids [35]. With this exception, in advanced patient-specific models it is usual to account for blood pressure simply by applying time-dependent distributed pressure loads on the leaflets surfaces.

ECG

During a cardiac cycle a wave of depolarization passes from the atrial pacemaker cells over the atrium and down the AV bundle to spread through the ventricular myocardial syncytium. Potentials from the heart are transmitted through the tissues and can be detected by electrodes to give an ECG recording. These potentials are attentuated as the signal passes through the tissues. Hence the size of the ECG signal detected is only 1 to 2 mV instead of the original potential of about 90 mV mentioned above. The larger the bulk of the cardiac muscle through which the waves of depolarization pass, the larger the potential detected at the surface, so there is a large QRS complex from the depolarization wave in the ventricles and a smaller P wave from the atria.

The actual appearance of the ECG depends on the position of the electrodes relative to the heart (Fig. 15.2). Because the atrial signal spreads outwards, the P wave is usually positive regardless of the electrode position. However, in the case of the ventricles the wave of depolarization travels downwards and to the left, so the QRS complexes vary in appearance according to the electrode position. With an oesophageal electrode positioned close behind the atria of the heart a particularly clear ECG signal of the P waves is obtainable. The time intervals in the complexes are important. For example, a PR interval of over 200 ms indicates delayed conduction from the atria.

Because other muscles give rise to potentials prior to contaction, the patient must relax and make no movement during the recording.

12.2 Echocardiographic approach to the LV contractility

During a cardiac cycle, the LV wall shortens, thickens, and twists along the long axis. Shortening and thickening can be quantified by measuring regional strains. Strain or myocardial deformation from developing forces is expressed as either the fractional or the percent change from the original dimension [17,18]. Positive radial strains represent wall thickening (radial deformation), whereas negative strains represent segment shortening (e.g., circumferential shortening, longitudinal shortening, and fiber shortening) [14].

Three perpendicular axes orienting the global geometry of the LV define the local cardiac coordinate system: radial, circumferential, and longitudinal.

Echocardiographic techniques like tissue Doppler imaging have excellent temporal resolution (± 4 ms) and could be used for the assessment of myocardial deformations [14] (see Chapter 2).

The base and apex of the LV rotate in opposite directions. Twist defines the base to apex gradient in the rotation angle along the longitudinal axis of the LV and is expressed in degrees per centimeter [9,23]. Torsion and twist are equivalent terms. Torsion can also be expressed as the axial gradient in the rotation angle multiplied by the average of the outer radii in apical and basal cross-sectional planes, thereby representing the shear deformation angle on the epicardial surface (unit degrees or radians) [23]. This normalization can be used as a method for comparing torsion for different sizes of LV. When the apex-to-base difference in LV rotation is not normalized, the absolute difference (also in degrees or radians) is stated as the net LV twist angle [24].

Speckle-tracking echocardiography (STE) has emerged as an alternative technique [25] (see Chapter 2). The robustness and the clinical applicability of that technique are nowadays only validated for the assessment of global longitudinal strain [26,27]. When considering regional longitudinal strains, there are inaccuracies according to the software used. Longitudinal LV mechanics, which are predominantly governed by the subendocardial region, are the most vulnerable component of LV mechanics and therefore most sensitive to the presence of myocardial disease. The first of them is the ischemic etiology that will affect first the subendocardium. The mid-myocardial and epicardial function may remain relatively unaffected or weakly affect in patients with HF and preserved LV EF. Circumferential strain and twist may remain normal or show exaggerated compensation for preserving LV systolic performance. Increase in cardiac muscle stiffness, however, may cause progressive delay in LV untwisting. Loss of early diastolic longitudinal relaxation and delayed untwisting attenuate LV diastolic performance, producing elevation in LV filling pressures and a phase of predominant diastolic dysfunction, although the LV EF may remain normal. The diagnostic of these HF with preserved ejection that most affect the subendocardium could be very difficult and might require submaximal exercise stress echocardiographies [28]. It has not been proposed in past recommendation, but that could change [29].

On the other hand, an acute transmural insult (like a myocardial infarction) or progression of disease results in concomitant mid-myocardial and subepicardial dysfunction, leading to a reduction in LV circumferential and twist mechanics and a reduction in LV EF. Assessment of myocardial function, therefore, can be tailored per the clinical goals. The detection of altered longitudinal function alone may suffice if the overall goal of analysis is to detect the presence of early myocardial disease. Further characterization of radial strains, circumferential strains, and torsional function provides assessment of the transmural disease burden and provides pathophysiologic insight into the mechanism of LV dysfunction [30]. For instance, the pathophysiologic process such as radiation that affects both the pericardium and the subendocardial region may produce attenuation of both longitudinal (first) and circumferential (afterwards) LV function [31]. Several studies have reported the strain values in patients with systolic HF (Table 12.1), HF with preserved LV EF, and hypertrophied cardiomyopathies. The data proposed in Table 12.1 are rather convergent; however, these measurements of LV systolic longitudinal strains are not used or proposed in guidelines such as in those for HF with preserved LV EF.

Table 12.1. Principal studies published in the field of heart failure with depressed LV ejection fraction

GLS, global longitudinal strain.

As a rule of thumb, a global longitudinal strain less than − 17% is an independent parameter of severity of the cardiomyopathy [33]. In HF with preserved LV EF, the prognostic cut-off that is most frequently reported is − 16% [38].

In more complex cardiomyopathies like those induced by anthracyclins, it seems that as soon as the global longitudinal strain is less than − 19%, physicians have to carefully monitor the patients. Studies are ongoing to know whether dedicated treatments like ACE-inhibitor and B-blockers should be introduced [26].

Although strain data are valuable in patients with systolic HF, the indication for an ICD or a biventricular pace maker remains dependent upon the degree of LV dysfunction as determined by the LV EF (Figures 12.1 and 12.2). The LV EF should be measured, according to recommendations using the apical four- and two-chamber views using the Simpson method. The M mode should not be used especially in hearts having a spherical remodeling.

In the present and even more in the very near future, real-time 3D echocardiography (RT3DE) should improve the robustness and reproducibility of the echo data [39–41]. It is not yet available everywhere (see Chapter 2). Still, improvements in transducer are required for the actual transfer of the 3D approach in clinical practice. Feasibility remains lower than for the 2D approach [42,43]. It has been demonstrated that in patients in whom serial examinations are obtained, the 3D echocardiographic approach is the most reliable [39,44].

Other approaches are available (Figures 12.1–12.4) [25,45]. Pulse tissue Doppler is the most relevant and is a way for assessing LV longitudinal systolic function as well as MAPSE.

In addition to these measurements (LV EF required, global longitudinal strain, or pulse tissue Doppler), one must measure the LV stroke volume (Doppler and volumetric approaches) for estimating the cardiac output and finally the efficacy of this LV contractility to eject enough blood in the arterial tree (Figure 12.5).

Also, as already mentioned, stress tests might be required to look for contractile reserve, in particular. Without going into much detail in regard to the technique, dobutamine could be used, but submaximal exercise stress echocardiography is probably the ideal approach to test the systolic response and the diastolic response of the failing heart. In HF with preserved ejection, the absence of systolic and diastolic reserve has already been mentioned. In ischemic heart disease, it has to be tested; sometimes, one is “surprised” to observe that without any acute ischemia, the exercise unmasks a dynamic functional mitral regurgitation that might be very useful for understanding the symptoms and is perhaps the best treatment of a patient with systolic HF [46].

In addition to the assessment of viability or contractile reserve, it might be necessary to look for myocardial ischemia. The techniques are the same as in a non-failing heart, being nevertheless aware of the risk of maximal dobutamine stress test in patients with a failing heart (risk of ventricular arrhythmia, in particular).

6.6.5 High-Resolution ECG

For many years the interpretation of resting ECGs was based on measurements derived from waves whose amplitude were at least several tens of microvolts; waves with smaller amplitudes were ignored since these were almost always caused by noise. This limitation was, however, removed with the advent of the high-resolution ECG with which it became possible to detect signals on the order of 1 µ V thanks to signal averaging techniques (therefore, these signals are sometimes denoted “micropotentials”). The high-resolution ECG has helped unlock novel information and has demonstrated that signal processing for the purpose of noise reduction is a clinically viable technique. The acquisition procedure is usually the same as for the resting ECG, except that the signal is recorded over an extended time period so that a sufficiently low noise level is attained, i.e., sufficiently many heartbeats must be available for averaging.

In contrast to the averaging of evoked potentials, where information is available on when the external stimulus is elicited, the time reference (“fiducial point”) must be determined from each individual heartbeat before ensemble averaging can be performed. The fiducial point must be accurate, otherwise low-amplitude, high-frequency components of the ECG will be distorted by smearing (cf. Section 4.3.6 on the effects of latency shifts). The high-resolution ECG rests on the assumption that the signal to be estimated has a fixed beat-to-beat morphology, whereas signal averaging during exercise must be able to track slow changes in morphology. Since the highresolution ECG is often expected to contain high-frequency components, the sampling rate is at least 1 kHz (a lower sampling rate is sufficient in the other, above-mentioned ECG applications).

Several subintervals of the cardiac cycle have received special attention in high-resolution ECG analysis, and low-level signals have been considered in connection with

the bundle of His which depolarizes during the PR segment, i.e., an interval which in the resting ECG is considered silent [44, 45,

the terminal part of the QRS complex and the ST segment where late potentials may be present [46–48],

intra-QRS potentials [49–51], and

the P wave [52–54].

Of these four applications, the analysis of late potentials has received the most widespread clinical attention. Late potentials may be found in patients with myocardial infarction where ventricular depolarization can terminate many milliseconds after the end of the QRS complex (Figure 6.20). This prolongation is due to delayed and fragmented depolarization of the cells in the myocardium which surround the dead region (scarred tissue) caused by infarction; the conduction capability of the bordering cells is severely impaired by infarction. Many studies have demonstrated the importance of late potentials when, for example, identifying postinfarct patients at high risk of future life-threatening arrhythmias [55].

Remodeling of myofiber orientation

During simulation of the cardiac cycle, the myofiber orientation e→f,0 in the unloaded state changes into the actual myofiber orientation e→f , due to deformation of the tissue. In addition, remodeling of the extracellular matrix in response to load-induced damage and regular collagen turnover is considered to cause a structural change of the myofiber orientation e→f,0 in the unloaded state. The conceptual model of this process of remodeling of myofiber orientation is explained in detail in Fig. 2. To describe remodeling induced changes, we used the model by Kroon et al. (2009b), in which myofiber orientation changes according to the following evolution equation:

(8)∂e→f,0∂t=1κ(e→f*−e→ f,0)

with κ representing the adaptation time constant, which was set to four times the cardiac cycle time. e→f* is the actual myofiber orientation in the deformed tissue, corrected for rigid body rotation:

(9)e→f =F⋅e→f,0λf =R⋅U⋅e→f,0 λf=R⋅e→f*;λf=|U⋅e→f,0 |

with λf the myofiber stretch ratio and F the deformation gradient tensor that consists of the actual deformation U and a rigid body rotation R. Rigid body rotations are not taken into account for adaptation, because they cannot be sensed by the tissue. Myofiber reorientation only occurs if the unloaded fiber direction e→f,0 does not coincide with any of the principal strain directions (eigenvectors of U), that is, in case of fiber cross-fiber shear. On the endo- and epicardial surfaces, the myofiber vector resulting from Eq. (8) was modified by projecting it onto the surface to ensure that myofibers do not stick out of these surfaces.