These numbers and their ranges are taken from a normal group of individuals. One has to always remember that body size at times has to be taken into consideration. For example, in the very large person or the very small person, one has to consider the proportional size of a vessel or chamber and indexed to body surface area as is done in children. In other situations, such as the athletic individual, the “normal” may be outside of the standard limits. Therefore, these values are relative and must be individualized for each clinical situation.

In addition to left ventricular dimensions, left ventricular mass can be calculated by several methods. Using M-mode and assuming that the left ventricle is prolate ellipse, one can calculate the LV mass, and using 2D, the mass can also be calculated. The 2D calculations are based on either the formula for a truncated ellipse or the area length method. Once the volume is calculated, the myocardial density is factored as 1.05 g/mL. The most validated measurements are from the M-mode method, and normal values are 95 g/m² for women and 115 g/m² for men. 2D measurements are slightly different with 88 g/m² for women and 102 g/m² for men. 3D may show the most promise but is a work in progress at this point in time. These parameters offer information about the prognosis and longitudinal follow-up of conditions such as left ventricular hypertrophy. Three-dimensional methods may be more accurate but at this point need more validation.

The function of the left ventricle has to do with a pulsatile pump. Once filled, it squeezes, closes the mitral valve, and opens the aortic valve. The output of the pump is measured by the volume of each stroke and the pulse rate. The stroke volume results from filling of the left ventricle and ejection of a fraction of this volume. The heart cannot eject all of its contents with each beat. At rest, about 55% or 60% of the contents of the left ventricle are ejected with each beat, and with exercise, this number can increase to the 80% range. If the myocardium becomes weakened by a disease process, it becomes dilated, and a new position on the Frank-Starling curve becomes operative to maintain stroke volume. Larger volumes of blood that are present at the end of diastole along with larger dimensions of the chamber tend to compensate for the weakened myocardium and maintain cardiac output and cardiac reserve. Volume increases do not come without the price of increased pressures within the left ventricle, the left atrium, and secondarily the pulmonary circuit.⁴

The shape of the left ventricle allows for efficient squeezing and twisting to take place. The normal left ventricle consists of three layers, an epicardial layer (arranged in a left-handed helix), a midlayer (with a circumferential arrangement), and an endocardial layer (arranged in a right-handed helix), which allow for the twisting motion of the left ventricle. The longer left-handed helical epicardial fibers pull the apex in a counterclockwise in the short axis and the base clockwise when both are viewed from the apex. Once this rotation has occurred, energy is stored and later used in the untwisting process that allows blood to be sucked into the left ventricle in diastole. Untwisting is also an energy-using process. The combination of the action of each of these layers allows the twisting motion of the left ventricle to have efficient squeezing effect and ejection of blood
yet takes advantage of the limited capability of sarcomeres to contract in their narrow range of efficiency (optimally in the 13% range).¹

Each of these layers has its own specific function both mechanically and electrically. The thickest region of the left ventricle is the basal portion with the thinnest region being the apex. The smaller radius and the thinner will of the ventricle at the apex allow maintenance of wall stress as described by the law of Laplace. The myocardial wall may hypertrophy in response to afterload or may thin in response to injury and dilatation. The walls may be compliant and respond to volume at a low pressure or be “stiff” and respond to volume at high pressure. This can be a global or a regional effect.

The rotation and the twisting effect in addition to longitudinal shortening cause the annular areas to descend toward the apex in systole.

Methods to assess the systolic function of the left ventricle center around the ejection fraction as calculated by various methods, analysis of segmental myocardial mechanics, indirect methods of analysis of Doppler profiles of flow, and time intervals between events.

The other half of the cardiac cycle, diastole, is evaluated by analysis of mitral Doppler inflow parameters, tissue Doppler velocities, and measurement of left atrial size.

In addition, the myocardium can be infiltrated by substances such as amyloid resulting in stiffening of the myocardium and dysfunction in systole and diastole. In rare instances, tumors can originate or metastasize to the myocardium. The myocardium can be constricted by a scarred pericardium or compressed by tense fluid present within the surrounding pericardial space. The left ventricle can also be affected by adjacent structures such as tumors of various origins. This section illustrates some of these abnormalities.

A lot takes place from P wave to P wave and also from the onset of the QRS complex and the end of the T wave. Not only is there systole and diastole but periods of isovolumic contraction and relaxation occur that have their boundaries as pressure curves intersect. It is an oversimplification to consider systole the period between aortic valve opening and closing and diastole the remainder of the time. Myocardial relaxation begins after ventricular ejection reaches its peak pressure and extends well into the period after aortic closure but not throughout the period from aortic closure and opening. Echocardiography offers a unique look at these events that occur during mitral and aortic opening and closing and their temporal relationships. Analysis of these intervals offers information about the contraction and reaction of the left ventricle.

The combination of Doppler parameters with imaging information allows for more analysis of cardiac function.

During the isovolumetric contraction period, the left atrial pressure remains relatively constant, so the gradient between the left ventricle and atrium remains relatively constant. The rate of rise (dP/dT) of the velocity curve reflects systolic function. If the velocity is calculated at 1 and 3 seconds, then the change in velocity in mm Hg can be calculated if the time interval is known. According to the Bernoulli equation, the pressure differential is (4 × 3²) – (4 × 1²) = 32 mm Hg for the time interval between 1 and 3 m/s. In this individual, the time interval was 47.2 ms. Therefore, the dP/dT for 1 second is 32 mm Hg/0.0472 = 678 mm Hg/s. The normal is >1000 mm Hg/s.⁸

Speckle tracking echocardiography allows identification of points or speckles in the myocardium and tracking of these speckles in time. The change in the length between two speckles from diastole to systole offers information about regional myocardial function. If one designates the initial length of a segment of the myocardium identified by speckles as L₀ and a final length as L, then this difference can be expressed as a percentage. This linear description of lengthening and shortening or deformation is referred to as Lagrangian strain.

Strain is a negative number for the left ventricle, and global strain is -20% or a more negative number such as -24%.

Since the initial length (L₀) is longer than the final length (L), the numerator will be a negative number and strain will be a negative number or percentage (normal for the left ventricle -20% or higher). In the case of circumferential strain, the same is true in that the strain is expressed as a negative number for normal segments. For radial strain that represents thickening, the initial numbers are smaller than the final numbers, so a positive percentage is obtained. Rotation of the base of the heart in a clockwise direction and the apex in a counterclockwise direction results in a twisting motion. When these angles of rotation are quantified and added together, they give a sum that is called twist. Strain rate is an expression of the rate of change of length between two points normalized to the distance between them and calculated by (V_a – V_b)/D where (V_a – V_b) is the velocity difference between two points and D is the distance between them. It is expressed in 1/seconds.⁹,¹⁰,¹¹

Longitudinal strain is measured using the speckle tracking method. These polar displays are constructed from three apical views that are combined to produce these maps. Normally, these are in the -25.1% range as is seen in Fig 2.8. In Fig 2.9, which is taken from an individual with severe dilated cardiomyopathy, the number for global strain is not calculated because some segments were not measurable and designated as “x.”

Rotation refers to the movement of the myocardium around the long axis of the ventricle and in the above example is +18° in a counterclockwise manner as designated and viewed from the apex. The systolic rotation in this example is -16° in a clockwise manner as viewed from the apex. Twist refers to the difference of these two angles or the net twist angle of 18 + 16 = 34°. Torsion refers to the difference in these angles as they relate from the apex to base dimension expressed in degrees per centimeter.¹²

This process evolves from infancy where apical rotation remains constant and subsequently the basal rotation transitions from counterclockwise to clockwise, the usual adult pattern. With aging, twist increases primarily due to less basal clockwise rotation and thus less opposition to apical counterclockwise rotation all due to decrease in subendocardial function.¹³

The E wave is the manifestation of early diastolic filling of the left ventricle. It is generated by the suction effect within the left ventricle by factors such as elastic recoil and the active untwisting process. This is an energy-requiring process that is produced by the undoing of the squeezing and twisting that occurs in systole. It has three components to include active relaxation, restoration of forces, and lengthening of load.¹⁹ In young individuals, these processes are very prominent and result in a dominant E wave associated with the very vigorous suction effect associated with elastic recoil and untwisting of the left ventricle. Filling is so vigorous in early diastole that there is little left for the atrium to do and thus a small A wave is often present. In younger individuals, the E wave is dominant; however, by the sixth or seventh decade of life, the E and A waves are equal. When pressures of the left ventricle increase, filling volumes of the left ventricle in early diastole decrease, and the role of atrial systole becomes more important producing a prominent A wave that is higher than the E wave. In older individuals, the E wave decreases because of prolonged relaxation.²⁰ When left atrial pressure increases to compensate for the higher filling pressures, the E wave becomes prominent again and is taller than the A wave, and the pseudonormal pattern develops. High gradients between the left atrium and left ventricle allow for a high-velocity E wave of brief duration and a rapid deceleration time after reaching maximum velocity. The A wave decreases with higher grades of diastolic dysfunction, and its duration has an important relationship to the pulmonary Ar as the difference between these two parameters relates to left ventricular end-diastolic pressure. These advanced grades of diastolic dysfunction can be altered by altering left atrial pressure with Valsalva maneuver producing a longer deceleration time and thus assuming a lesser degree of diastolic dysfunction. This phenomenon is described as the reversible pattern of diastolic dysfunction and has a more favorable prognosis. Otherwise, if this reversible phenomenon does not occur, the restrictive filling pattern is irreversible and has prognostic importance.

Other parameters such as mitral annular tissue Doppler velocities, left atrial volume, tricuspid regurgitation jet velocity along with mitral inflow flow propagation, and pulmonary vein flow velocity profiles all have characteristic alterations as left ventricular diastolic dysfunction progresses from abnormal relaxation to irreversible left ventricular filling.²¹

In this simultaneous tracing of the left ventricular and left atrial pressure curves and mitral Doppler inflow, several points are illustrated. We must remember that gradients give rise to velocities and understanding of pressure relationships makes for understanding of velocities. Upon pressure falling within the left ventricle, relaxation occurs beginning after the peak LV pressure and extends to the point near peak diastolic flow velocity across the mitral valve. Note that relaxation begins after the peak of the LV pressure and extends into diastole to a variable degree. When the left ventricular pressure falls below that of the left atrium, the mitral valve opens and flow begins into the left ventricle. The velocity across the mitral valve is related to the maximum pressure gradient as illustrated by the difference between the two curves. Diastasis occurs after these events, and the atrium contracts later.²¹

A stop frame in early diastole at a time when the mitral leaflets are open and early diastolic flow is taking place writes the E wave on the pulsed Doppler tracing. Sampling this phenomenon is done in the region of the red dot within the left ventricle at the tip of the mitral leaflets. The yellow dots are located at the myocardial segment within 1 cm of the mitral annulus and are the location for sampling of tissue Doppler velocities. The pulsed-wave Doppler sampling of the pulmonary vein flow velocities is done 1-2 cm within the superior pulmonary vein with the sample box adjusted to 3-4 mm. Acquisition of pulsed-wave Doppler images for measurement of mitral A wave duration is done at the level of the mitral annulus illustrated by the blue dot.

The normal velocity filling pattern of the left ventricle is measured at the tips of the mitral leaflets with pulsed-wave Doppler. The E wave is usually the most prominent wave and is related to active early diastolic filling. In young individuals, the initial filling is vigorous and is due to elastic recoil and the active energy-requiring untwisting process. Sometimes, early diastolic filling is so vigorous that there is little left for the atrium to do. Therefore, in young individuals, the E wave is very large and the A wave is small. A period of diastasis occurs and is followed by the velocity curve caused by atrial contraction, the A wave. Normally, the E/A ratio is between 1 and 2, and the mitral deceleration time is between 150 and 240 ms. Normally, the A wave duration is in the 79-153 ms range, and the A velocity is typically 19-35 cm/s in normal individuals 40 years or less.^*16,²²

The duration of the mitral A wave should be measured at the level of the mitral annulus and not at the tips of the leaflets. In normal individuals, these intervals are similar; however, as left ventricular filling pressures rise, the pulmonary “A” wave reversal duration begins to increase, and the difference between these two values quantitatively relates to left ventricular filling pressures. Values vary according to age and the state of atrial and ventricular function.

Tissue Doppler imaging can be used to measure the velocities of the septal and lateral annular velocities. During systole, the apex is relatively stable and the mitral annulus descends along the long axis of the left ventricle. The rate and magnitude of this decent (manifest by the s′ wave) is related to systolic function of the ventricle. During diastole, the motion of the mitral annulus (manifest by the e′ and a′ waves) is related to the diastolic function of the left ventricle as it relaxes and fills. The magnitude of these velocities (of myocardial tissue) is about
one-tenth of those of erythrocytes. That is, if the left ventricular outflow velocity (erythrocytes targeted) is 1 m/s per second, the mitral annular tissue velocities in systole and diastole are in the range of 0.1 m/s. These velocities are measured by placing sample volumes within 1 cm ventricular to the mitral annulus with sweep speed increased to the 50-100 mm/s range. Instrumentation allows recording of low velocities and filtering out of high velocities, and high frame rates are required. Values are obtained from the septal and lateral annular areas. Velocity scale should be set to about 20 cm/s above and below the baseline. There is a slight difference in the values obtained for the septal and lateral locations with the septal being slightly lower than the lateral. This is due to differences in rotational effects and the influence of the right ventricle. In healthy young individuals, the septal e′ velocities are usually >7 cm/s, and the lateral e′ velocities are >10 cm/s. Exceptions to this are in individuals with regional wall motion abnormalities such as lateral myocardial infarction, right ventricular enlargement, constrictive pericarditis, and others.¹⁶,¹⁷,²³ Constrictive pericarditis results in tethering of the lateral annular area and causes the phenomena of “annulus reversus” with the septal velocities being higher than the lateral. In the setting of constrictive pericarditis, the e′ is typically increased, and therefore, there is an inverse relationship between E/e′ and LV filling pressures, a phenomenon called “annulus paradoxus”.²⁴,²⁵

In normal individuals, the E wave increases with preload and with exercise and the e′ follows. In those individuals with abnormal relaxation, the e′ is reduced and does not increase as much as preload changes. In the setting of diastolic dysfunction as preload increases and filling pressures increase, the E wave increases and the e′ wave decreases. Therefore, the ratio of these two (E/e′) is related to left ventricular filling pressures and pulmonary capillary wedge pressures. Using the guideline-recommended values for assessing diastolic dysfunction, for E/e′ average, a ratio of >14 is abnormal, and for the E/e′, a septal ratio of >15 and E/e′ lateral ratio of >13 are abnormal. These ratios along with the mitral tissue Doppler velocities, the tricuspid regurgitant jet velocity, and the left atrial volume index and other parameters are used in the assessment of diastolic function.¹⁶,¹⁷,²³

Special situations in which E/e′ and other parameters of diastolic dysfunction may not accurately predict left ventricular filling pressures are noted in Tables 2.1 and 2.2.

The mitral annulus descends toward the apex in systole and ascends back to the baseline position in diastole. The apex remains relatively stable. The velocities of this motion can be measured with pulsed-wave Doppler using a sample volume of 2-5 mm in size and placed at the mitral annulus at or just below the leaflet attachments. The velocity scale should be set at ˜20 cm/s above and below the zero-velocity baseline with minimal angulation between the ultrasound beam and the plane of cardiac motion, and sweep speed should be set at 50-100 mm/s with recordings done at end-expiration.

The left atrium is the entrance way to the left ventricle, and its size gives immediate information as to the systolic and diastolic function of the heart.

The following sections illustrate the parameters used for assessment of diastolic function in the presence of:

Recommendations for these parameters are in recent document ASE/EACVI Guidelines and Standards published in the Journal of the American Society of Echocardiography.¹⁷

In addition, an alternative approach recently published offers an alternative to the classification of diastolic dysfunction.¹⁸

Since validation of these classifications is a work in progress, the second classification algorithm is presented. The physiology is the same, and familiarization with the physiology of diastole is needed to fully understand these classifications.

Interest in diastolic function of the heart has risen in recent years in the setting of the epidemic of heart failure with preserved ejection fraction (HFpEF). This entity may account for up to 50% of all individuals presenting with heart failure, and furthermore, the prognosis in this group may be similar to those with heart failure with reduced ejection fraction (HFpEF). In the setting of older age, female gender, diabetes, obesity, systemic arterial hypertension, and left ventricular hypertrophy, the prevalence and importance of the diagnosis of HFpEF become very important. Echocardiography assumes a primary role in making this diagnosis by the analysis of events in the diastolic phase of the cardiac cycle. Mitral inflow Doppler parameters, tissue Doppler, left atrial size, and tricuspid regurgitation jet velocity along with other parameters are useful in the assessment of diastolic dysfunction. Numerous studies are available for review on this subject.²⁶,²⁷ The ASE/EACVI guidelines¹⁶ are available along with a 2016 update.¹⁷

Assessment of diastolic function by echocardiography by using the above parameters will be illustrated in the following examples outlined in Table 2.3.

The guidelines for individuals with normal LVEF have been simplified to the four variables, and their abnormal cutoff values are listed above. It has been recommended that more than half of these parameters be abnormal before the diagnosis of diastolic dysfunction is made. The diagnosis of diastolic dysfunction is inconclusive if only half of the abnormal cutoff values are present. See the algorithm from guidelines on normal ejection fraction.¹⁷