Ebook A practical approach to clinical echocardiography (E): Part 2

(BQ) Part 2 book “A practical approach to clinical echocardiography” has contents: Diastolic function, tissue doppler echocardiography - current status and applications, rotation, twist and torsion, congenital heart disease in adults, pericardial diseases, ischemic heart disease, cardiomyopathies, tumors, masses and infection,… and other contents.

ˆ INTRODUCTION

Importance of the right ventricle (RV) in health and

disease has seen a sea-change from being just a

conduit to an important contractile chamber, which

significantly impacts cardiac physiology, hemodynamics

and development of symptoms.1 It is the final barrier

between compensated versus decompensated heart

Right ventricular musculature when stressed expresses

several important enzymes and activates several signal

transduction pathways involved in hypertrophy, fibrosis

and pulmonary vasoconstriction.2 These changes bring

new meaning to pharmacotherapy of heart failure and the

role of the RV Under normal conditions, the RV is coupled

with a low-impedance, highly distensible pulmonary

vascular system (Figs 11.1 to 11.3)

Compared withthe systemic circulation, pulmonary

circulation has a much lowervascular resistance and

greater pulmonary artery distensibility.3 Under normal

conditions, right-sided pressures are significantly lower

than comparable left-sided pressures Despite this, the RV

ejects similar or somewhat greater volume during systole

compared to the left ventricle (LV) 4–6 (Figs 11.4 and 11.5)

ˆ PECULIARITIES OF THE RIGHT VENTRICLE

• The right ventricular systolic function is predominantly

afterload-dependent and minimally affected by the

preload

• Unlike the LV, there is no torsion of any significance and hence hardly any circumferential shortening (Fig 11.6)

• Radial shortening is unimpressive unlike the LV, partly because myofiber orientation and muscle volume is different (Fig 11.7)

• Highly trabeculated and spongy appearance of the cavity allows it to work as an efficient volume pump but poses challenges with regard to geometric volume estimations7 (Fig 11.8)

Fig 11.1: Schematic diagram of low impedance right heart circulation Short-axis view.

Fig 11.2: Distribution of pulmonary artery systolic pressure in normal

subjects.

Fig 11.3: Distribution of pulmonary artery mean pressure in normal subjects A mean pressure ≥ 25 mm Hg indicates presence of pulmo- nary hypertension.

Fig 11.4: Right ventricular pressure-volume loop. Fig 11.5: Comparison of pressure-volume loop of the right ventricle

(yellow) with that of the left ventricle (white).

• Presence of a transverse moderator band prevents

undue chamber dilatation and hence despite

signi-ficant combined pressure and volume overload in

heart failure, it is not uncommon to see minimum

geometric alterations.8 This makes eye-balling highly

deceptive in assessing right ventricular function

(Fig 11.9)

• In advanced diseased states, outflow may become

a dominant contractile chamber by virtue of its

circumferential muscle orientation Little attention

has been given to the importance of this phenomenon

• There are phases in cardiac cycle, which have variable functional importance and temporal dimension needs

to be coupled with a mechanical event for complete

Fig 11.6: Right ventricular basal circumferential strain of only -4% in

a normal subject Paradoxically, many segments show circumferential

lengthening.

Fig 11.7: Comparison of basal right ventricular radial strain (10%) with the left ventricular basal radial strain (55%) in a normal subject.

Fig 11.8: Transthoracic echocardiography short-axis view showing

spongy right ventricle.

Fig 11.9: The right ventricle is a tripartite structure with an inflow part including the tricuspid valve apparatus; a trabecular part that includes pronounced trabeculations that function as an absorptive sponge, fill- ing during diastole and releasing blood in systole; and an outflow tract that consists of a muscular infundibulum, separating the tricuspid from the pulmonary valve.

Fig 11.10: Conceptual diagram The two contractile chambers of the

right ventricle with distinct morphologies.

assessment Thus, a pressure–volume loop during a single beat in temporal domain is possibly the best way of assessing function.10 However, it is clinically impractical to obtain this information by a convenient and reproducible method So, we look for surrogates and correlates

• In spatial domain, fractional area change or ejection fraction or volume leftover at end-ejection are parameters of function (Figs 11.12A and B)

• In temporal domain, ejection period or filling period

or a ratio of time spent during isovolumic phase to ejection phase provide functional information of clinical value

• Typically, the RV spends less time during isovolumic

phase compared to the LV and hence it is more

energy-efficient (Fig 11.13) Increase in this period is the early

indication of the failing RV

• The right ventricular ejection time is about

30–50 milliseconds longer because of the outflow

chamber, which contracts near the end of systole

• The right ventricular ejection period shows phasic

variation with increase during inspiration

• Lack of phasic variation may suggest onset of

dysfunction if there is no abnormal interchamber

communication (Fig 11.14)

• Indirect assessment of the right ventricular function

includes integrity of inflow valve and the outflow

valve Fortuitously, there are ubiquitous tricuspid and

pulmonary valve leaks, which can provide information

on preload, afterload and forward vascular resistance (Figs 11.14 and 11.15)

• Slopes of tissue velocity propagation during lumic phase do correlate with intrinsic contractility (Fig 11.16)

isovo-• Geometric alterations are not an indicator of dysfunction but suggest that the latter may be present

or will occur in future

• Quantum and speed of longitudinal motion of this complex chamber has also found clinical utility, because most deep fibers of the RV are longitudinally arranged Longitudinal motion has fair correlation with ejection performance

• Patterns of flow and tissue movements also help in detecting abnormalities in pressure–volume loops and provide some meaningful information

Fig 11.11: Transthoracic echocardiography short-axis view Complex geometry of the right ventricular chamber; inflow on the left side, lar portion in the middle and the conus on right side The right ventricular outflow tract (RVOT) becomes an important contractile chamber in diseased states.

trabecu-Figs 11.12A and B: Estimation of the right ventricle function by optimizing a transthoracic echocardiography four-chamber view Fractional area change and end-systolic volume can be estimated.

Fig 11.13: Right ventricle free wall tissue velocity image Note that

isovolumic contraction (IVC) and isovolumic relaxation (IVR) periods

are very brief.

Fig 11.14: Continuous wave Doppler interrogation of the right tricular outflow tract Physiological pulmonary regurgitation with a peak diastolic velocity of 2 m/s is observed Note the duration of regurgi- tation increasing during expiration and decreasing during inspiration

ven-Lack of phasic variation is a sign of dysfunction.

Fig 11.15: Physiological tricuspid regurgitation jet with a peak

veloc-ity of 2.68 m/s Note the respiratory variation A peak transtricuspid

velocity ≥ 3.5 m/s is suggestive of elevated right ventricular systolic

pressure and velocities between 2.8 and 3.4 m/s are of borderline

significance.

Fig 11.16: Right ventricle (RV) free wall tissue velocity profile Note the difference between acceleration slopes in left (normal subject) and right panel [inferior myocardial infarction (INF MI) with possible

RV infarction).

AND PRESSURES

• Preload is an important determinant of the right

ventricular function A crude measure of the preload

is right atrial pressure or right ventricular end-diastolic

pressure

• It is difficult to measure right atrial volume or the right

ventricular diastolic volume by echocardiography

• Respiratory variations in filling may be better markers

of preload11 (Figs 11.14 and 11.15)

• Right atrial pressure or RV end-diastolic pressure can

be measured directly during right-heart catheterization

or estimated noninvasively by assessing inferior vena cava diameter and collapse index.12 Dilated (≥ 20 mm) and noncollapsing inferior vena cava is suggestive of mean right atrial pressure ≥ 15 mm Hg (Fig 11.17)

A dilated inferior vena cava with inspiratory or

sniff-related collapse of < 50% indicates elevated mean

right atrial pressure (≥ 10 mm Hg)

• The annular tricuspid E/e ratio and annular tissue

Doppler relaxation time have also shown moderate

correlation with right atrial pressure.13

• Raised right atrial pressure can also be judged from

movement of the interatrial septum or the hepatic vein

flow spectrum14 (Figs 11.19 and 11.20) A decrease in

systolic wave and a marked increased in atrial reversal

wave in hepatic veins indicate raised right atrial

pressure

• Estimation of the right ventricular end-diastolic

pressure from the Doppler pulmonary regurgitation

signal can be a good surrogate when jugular venous pressure is added to the pulmonary end-diastolic pressure gradient

• Elevated right ventricular diastolic pressures can also

be judged from the presence of diastolic tricuspid regurgitation, diastolic antegrade flow across the pulmonary valve or from the patterns of pulmonary regurgitation (Figs 11.20 to 11.25)

• It is also possible to estimate –dP/dt from tricuspid regurgitation signal (Fig 11.26)

Pulsed wave Doppler tricuspid flow velocities can also be used for assessing RV diastolic function An E/A < 0.8 indicates abnormal relaxation A combined flow and

Fig 11.17: Dilated inferior vena cava indicates elevated right atrial

pressure Reduced inspiratory collapse is specific A collapse index <

50% is highly suggestive of right atrial pressure > 10 mm.

Fig 11.18: M-mode section of the inferior vena cava with reduced inspiratory collapse.

Fig 11.19: Transthoracic echocardiography four-chamber view at

end-diastole showing bulge of the interatrial septum to the left,

indi-cating right atrial pressure higher than left atrial pressure in diastole.

Fig 11.20: Prominent diastolic tricuspid regurgitation indicating elevated right ventricle diastolic pressures in a patient with dilated cardiomyopathy.

Fig 11.21: Flow Doppler alternans of the tricuspid regurgitation with

normal right ventricular systolic pressure Doppler alternans is

sugg-estive of global right ventricle dysfunction.

Fig 11.22: Operated tetralogy of Fallot in an adult showing antegrade diastolic flow across pulmonary valve (arrows), indicating elevated right ventricular diastolic pressure.

Fig 11.23: Rapidly decelerating pulmonary regurgitation jet with

end-diastolic antegrade flow across pulmonary valve (arrows)

sugg-estive of raised right ventricle end-diastolic pressure.

Fig 11.24: Continuous wave Doppler interrogation of the pulmonary regurgitation jet The pattern is classic of normal right ventricular diastolic pressure as estimated by end-diastolic gradient and mid-diastolic dip.

Fig 11.25: Restrictive transtricuspid pulsed wave Doppler flow

velocities A deceleration time varies with respiration, from 100 to

130 milliseconds Averaging five beats in quiet respiration is required

to obtain mean values.

tissue early diastolic velocity ratio E/e’ > 6 is also abnormal

A E/A ratio of > 2 with deceleration time < 120 milliseconds

is suggestive of restrictive RV diastolic function

Right Ventricular Volumetric Function

In clinical practice, the right ventricular ejection fraction (RVEF) is the most commonly used index of RV contra-ctility Although widely accepted, RVEF is highly depen-dent on loading conditions and may not adequately reflect contractility.15 Because the RV chamber is larger than the

LV chamber, RVEF is, under normal conditions, lower than LV ejection fraction The normal range of RVEF varies between 40% and 76% depending on the methodology used.16 Magnetic resonance imaging (MRI) is the most accurate method for measuring RVEF According to Lorenz et al.4 the normal value of RVEF is 61 ± 7%, ranging

from 47% to 76% RV images can be acquired in the

short-axis or long axial direction Alfakih et al.15 demonstrated

that the axial orienta tion resulted in a better intraobserver

and interobserver reproducibility than the short-axis

orientation The lower limit of radionuclide-derived

normal RVEF ranges from 40% to 45%.17 To be accurate,

volume assessment should always take into account the

complex shape of the RV Furthermore, the infundibulum

should be included in the volume measurement because

it can account for as much as 25% to 30% of RV volume.18

• The simplest and most routinely used method for

assessing RV volume includes linear dimensions and

areas obtained from single tomographic

echocar-diographic planes The best correlations between

single-plane measurements and RV volumes have

been obtained with the maximal short-axis dimension

and the planimetered RV area (in the four-chamber

view; Fig 11.27)

• Significant overlap has been noted, however, between

normal and volume-overloaded conditions, especially

for mild to moderate enlargement.18

• In an effort to be more accurate, different approaches

have been sought to directly measure RV volume

These include the area–length method and Simpson’s

approach In two-dimensional (2D) echocardiography,

numerous studies showed that the area–length method

that uses an ellipsoid or pyramidal model correlates

better with RV volume than Simpson’s rule.18 The

main difficulty seen with the application of Simpson’s

rule to 2D echocardiographic images is obtaining two

appropriate orthogonal views with a common long axis

• Three-dimensional (3D) echocardiography is a sing technique that could lead to more accurate assessment of RV volume.19,20 Echocardiography is less accurate than the nuclear methods Two-dimensional assess ment of RVEF with Simpson’s rule and the area–length method show moderate correlation with radionuclide- or MRI-derived RVEF.18 In the clinical setting, 3D echocardiography has also shown variable correlations with RVEF,19,20 although there have been some studies that have not supported the strong relationship Diffi culties include delineation of the anterior wall and identification of the infundibular plane

promi-• Right ventricle fractional area change represents the ratio of systolic area change to diastolic RV area It

is measured in the four-chamber view and can be incorporated systematically into the basic echocardio-graphic study A fractional area change of ≤ 35% indicates RV systolic dysfunction In diverse conditions,

a good correlation has been reported between RV fractional area change and RVEF21 (Fig 11.28)

Assessing Longitudinal Function

The RV contracts by three separate mechanisms:

1 Inward movement of the free wall, which produces a bellows effect

2 Contraction of the longitudinal fibers, which shortens the long axis and draws the tricuspid annulus toward the apex (Fig 11.29)

Fig 11.26: Estimation of dP/dt from tricuspid regurgitation (make it

yellow) signal Pressure drop from 1 m/s velocity to 2 m/s is multiplied

by the time taken to attain 2 m/s velocity.

Fig 11.27: Right ventricle short-axis dimension and area in four-chamber view are the two best correlates of the volumes.

Figs 11.28A and B: Fractional area change (44%) in a normal person estimated in four-chamber view.

Fig 11.29: Longitudinal shortening of the right ventricle free wall (-38%), which is nearly twice that of the interventricular septum.

3 Traction on the free wall at the points of attachment to

the LV There is no twisting or rotation (Fig 11.30)

Longitudinal motion is the predominant way of

ejection.22 Large surface area due to trabeculations

pro-duces effective stroke volume at low pressure.23 However,

it is difficult to assess area change accurately in any view

Tricuspid annular plane systolic excursion is another useful quantitative measurement of RV systolic performance24 (Fig 11.31) This method reflects the longi-tudinal systolic excursion of the lateral tricuspid valve annulus toward the apex It is usually measured with 2D-directed M-mode imaging in the four-chamber view Normal values are usually > 15 mm25 (Fig 11.31) Studies showed moderate correlation between tricuspid annular plane systolic excursion (TAPSE) and RVEF measured

by radionuclide angiography.26,27 However, some studies show better correlation between RVEF by MRI and TAPSE than with real-time 3D echocardiography.27 Measure-ments of tricuspid annular motion are easy to obtain, correlate with RV systolic function and have a high specificity and negative predictive value for detecting abnormal RV systolic function25 (Fig 11.32)

SYSTOLIC VELOCITY

Longitudinal motion of the RV can also be assessed by studying the tricuspid annular velocities Tissue Doppler imaging, which measures myocardial velocities, also allows quantitative assessment of RV systolic function 28,29

Fig 11.30: Right ventricle (RV) apical circumferential strain compared to the left ventricle apical one in a normal subject There is hardly any circumferential strain in the RV apex.

Fig 11.31: Tricuspid annular plane systolic excursion (TAPSE)

displayed in M-mode in a normal adult patient.

Fig 11.32: Tricuspid annular plane systolic excursion (TAPSE)

displayed in M-mode in an adult patient with hypoplastic right heart

syndrome Reduced TAPSE and post-systolic excursion are both

indicative of systolic dysfunction.

Fig 11.33: Tricuspid annular peak systolic velocity (TAPSV) of

12 cm/s (normal) in a 74-year-old male TAPSV does not decrease linearly with advancing age Reduced early diastolic velocity is indi cative of diastolic dysfunction.

(Fig 11.33) Systolic tissue Doppler signal of the tricuspid

annulus (TAPSV) has been studied as an index of RV

function in patients with heart failure (Fig 11.34)

Various cut-off limits have been proposed In one

study, peak systolic values < 11.5 cm/s identified the

presence of ventricular systolic dysfunction (RVEF

< 50%) with a sensitivity and specificity of 90% and

85%, respectively.28 A recent study has found good

discriminating power when compared to real-time 3D

echocardiographic ejection fraction when a threshold of

< 9.5 cm/s is used for predicting RVEF < 40%.30 A proposed

threshold value of < 10 cm/s is a good way to remember.25

This cut-off value predicts cardiac index < 2 L/min/m2 with

a sensitivity of 89% and specificity of 87%.31

Myocardial Performance Index

Right ventricular myocardial performance index (MPI), which is the ratio of isovolumic time intervals to ventri-cular ejection time, has been described as a nongeometric index of global ventricular function32 (Fig 11.35) It can be obtained either by superimposing tricuspid inflow and the

Fig 11.34: TAPSV of 6 cm/s indicative of right ventricle systolic

dysfunction Markedly prolonged isovolumic relaxation time (IVRT)

suggests abnormal myocardial performance index.

Fig 11.35: Assessment of myocardial performance index (MPI) from combined right ventricle inflow and outflow Doppler spectra.

right ventricular outflow Doppler flow, provided there are

no differences in heart rate Alternately, tissue Doppler

spectrum of the tricuspid annulus can be used to measure

isovolumic periods and ejection time

Right ventricular MPI appears to be relatively

independent of preload, afterload and heart rate, and

has been useful in assessing patients with congenital

heart disease, valvular heart disease and pulmonary

hypertension.33–35

The normal value of this index is 0.28 ± 0.04, and it

usually increases in the presence of RV systolic or diastolic

dysfunction A threshold value of > 0.50 is a good clinical

parameter.35 Its correlation with RVEF is modest, but

specificity is very high

Pseudonormalized MPI can occur in acute RV

myocardial infarction, which can probably be explained

by a decrease in isovolumic contraction time associated

with an acute increase in RV diastolic pressure.36

Other Parameters of Right Ventricle

Doppler Myocardial Imaging

Isovolumic acceleration (IVA) represents a new tissue

Doppler–derived parameter of systolic performance.37 It is

calculated by dividing the maximal isovolumic myocardial

velocity by the time to peak velocity: IVA = maximum

velocity/time to peak (Fig 11.36)

Vogel et al.37 studied the value of myocardial IVA in a

closed-chest animal model during modulation of preload,

afterload, contractility and heart rate Their study showed

that IVA reflects RV myocardial contractile function and

is less affected by preload and afterload within a logical range than either the maximum first derivative

physio-of RV pressure development (dP/dtmax) or ventricular elastance Clinical studies have confirmed its value in congenital heart disease, that is, after repair of tetralogy

of Fallot and in transposition.38 IVA positively correlates with global longitudinal strain and strain rate (SR) and negatively with MPI.38

There have been a few studies on the utility of early diastolic myocardial velocities of the tricuspid annulus and the RV free wall as a marker or global or diastolic dysfunction23 (Fig 11.37)

STRAIN RATE ANALYSIS

Strain is defined as the degree of deformation of an object, whereas SR represents the speed at which strain occurs Ultrasound-based Strain SR/strain imaging is a practical, reproducible clinical technique, which allows the calculation of regional longitudinal and radial defor-mation from RV segments Indices such as SR and strain are free of geometric assumptions and, thus, may provide new insights into right ventricular function.39 Both these indices correlate with multiple parameters of RV systolic function In echocardiography, RV longitudinal strain can be assessed reliably from apical views, whereas radial strain is difficult and is hampered by near-field artifacts and extremely small computational distance

Fig 11.36: Isovolumic acceleration (IVA) Time velocity integral

(TVI)-based right ventricle contractility index: isovolumic velocity from

first sharp peak during systole at onset of QRS/time to peak velocity In

the Figure shown, this value is 12/0.025 = 4.8 m/s 2 Normal values are

> 1.5 m/s 2

Fig 11.37: Markedly reduced tricuspid annular systolic and early diastolic velocities (3–4 cm/s) in a 64-year-old male patient with stable coronary artery disease The patient needed prolonged inotropic support following coronary artery bypass grafting (CABG).

In mathematical models and in experimental studies,

longitudinal strain appears to correlate best with changes

in stroke volume, whereas longitudinal SR is more related

to local contractile function and appears to be more

independent of loading 40 (Figs 11.38 and 11.39)

Strain and SR can be estimated either by Doppler

myocardial imaging or by non-Doppler 2D-strain using

acoustic speckle tracking or velocity vector imaging.38,40

The latter is gaining more ground because it is

angle-independent and more reproducible In a recent study,38

good correlations were found between RVEF and free wall

SR and strain

Right ventricle, septal systolic strain and SR may

allow the recognition of early RV dysfunction even when

conventional RV systolic parameters are normal.41

The RV, an underestimated chamber, is affected by

primary disorders of the right heart diseases, which affect

both ventricles concomitantly as a result of ventricular

interdependence when the LV alone is involved and

secondary to back-pressure effects Knowledge about the

role of the right ventricular function in health and disease

has lagged behind that of the LV However, seminal

work has been published in the past two decades It is

a thin-walled chamber with complex geometry, heavy

trabeculations, three distinct parts and three distinct

muscle bundles There is now increasing information

about the importance of the RV in patients with stable

coronary artery disease, heart failure, acute myocardial

infarction, pulmonary hypertension, Eisenmenger syndrome, adult congenital heart disease, response to drug therapy, exercise capacity in various disorders and valvular heart disease Right ventricular volumetry and ejection fraction estimation unlike that of the LV is a tedious, less robust and less validated parameter of the right ventricular function despite use of real-time 3D echocardiography In clinical practice, assessment of right ventricular function is a combination of several parameters that include estimation of its size and mass, movement of tricuspid annulus plane, peak systolic velocity of the tricuspid annulus motion, global myocardial performance index, estimation of the Doppler and non-Doppler–derived strain and SR of the RV in general and its free wall in particular, and estimation of the right ventricular systolic and diastolic pressures by flow Doppler spectrum of tricuspid and pulmonary regurgitations Global longitudinal strain of the RV by acoustic speckle tracking appears to be a very robust technique that needs further cross-sectional and longitudinal studies and its impact on prognosis in diverse disorders Impetus to this field has been given by competing techniques like MRI and computed tomography CT

Fig 11.38: TVI-based strain of right ventricle free wall in a normal

subject Longitudinal Doppler strain is -27% (normal > -20%). Fig 11.39:hypoplastic right heart syndrome Global systolic strain is markedly Two-dimensional longitudinal strain in an adult patient with

reduced (-7.7%) and there is evidence of post-systolic strain in right ventricle free wall along with paradoxical strain in the interventricular septum.

Disease: A Textbook of Cardiovascular Medicine, 7th

edi-tion Philadelphia, PA: Elsevier; 2005.

8 Haupt HM, Hutchins GM, Moore GW Right ventricular

infarction: role of the moderator band artery in

determin-ing infarct size Circulation 1983;67(6):1268–72.

9 Brown KA, Ditchey RV Human right ventricular

end-systol-ic pressure-volume relation defined by maximal elastance

Circulation 1988;78(1):81–91.

10 Brimioulle S, Wauthy P, Ewalenko P, et al Single-beat

estimation of right ventricular end-systolic

pressure-volume relationship Am J Physiol Heart Circ Physiol

2003;284(5):H1625–30.

11 Michard F, Teboul JL Predicting fluid responsiveness in

ICU patients: a critical analysis of the evidence Chest

2002;121(6):2000–8.

12 Moreno FL, Hagan AD, Holmen JR, Pryor TA, Strickland

RD, Castle CH Evaluation of size and dynamics of the

inferior vena cava as an index of right-sided cardiac

func-tion Am J Cardiol 1984;53(4):579–85.

13 Abbas A, Lester S, Moreno FC, Srivathsan K, Fortuin D,

Appleton C Noninvasive assessment of right atrial

pres-sure using Doppler tissue imaging J Am Soc Echocardiogr

2004;17(11):1155–60.

14 Appleton CP, Hatle LK, Popp RL Superior vena cava and

hepatic vein Doppler echocardiography in healthy adults

J Am Coll Cardiol 1987;10(5):1032–9.

15 Alfakih K, Plein S, Bloomer T, Jones T, Ridgway J,

Sivanan-than M Comparison of right ventricular volume

meas-urements between axial and short axis orientation using

steady-state free precession magnetic resonance imaging

J Magn Reson Imaging 2003;18(1):25–32.

16 Jain D, Zaret BL Assessment of right ventricular

func-tion Role of nuclear imaging techniques Cardiol Clin

1992;10(1):23–39.

17 Kjaer A, Lebech AM, Hesse B, Petersen CL Right-sided

cardiac function in healthy volunteers measured by

first-pass radionuclide ventriculography and gated blood-pool

SPECT: comparison with cine MRI Clin Physiol Funct

Imaging 2005;25(6):344–9.

18 Jiang L Right ventricle In: Weyman AE (Ed) Principle and

Practice of Echocardiography Baltimore, MD: Lippincott

Williams & Wilkins;1994:901–21.

sue imaging J Am Soc Echocardiogr 2003;16(9):906–21.

23 Brown GF Vascular pattern of myocardium of right cle of human heart Br Heart J 1968;30:679–86.

24 Hammarström E, Wranne B, Pinto FJ, Puryear J, Popp

RL Tricuspid annular motion J Am Soc Echocardiogr 1991;4(2):131–9.

25 Miller D, Farah MG, Liner A, Fox K, Schluchter M, Hoit

BD The relation between quantitative right ventricular ejection fraction and indices of tricuspid annular motion and myocardial performance J Am Soc Echocardiogr 2004;17(5):443–7.

26 Ueti OM, Camargo EE, Ueti AA, de Lima-Filho EC, Nogueira

EA Assessment of right ventricular function with Doppler echocardiographic indices derived from tricuspid annular motion: comparison with radionuclide angiography Heart 2002;88:244–8.

27 Kjaergaard J, Petersen CL, Kjaer A, Schaadt BK, Oh JK, sager C Evaluation of right ventricular volume and func- tion by 2D and 3D echocardiography compared to MRI Eur

30 De Castro S, Cavarretta E, Milan A, et al Usefulness of cuspid annular velocity in identifying global RV dysfunc- tion in patients with primary pulmonary hypertension: a comparison with 3D echo-derived right ventricular ejec- tion fraction Echocardiography 2008;25(3):289–93.

31 Rajagopalan N, Saxena N, Simon MA, Edelman K, Mathier

MA, López-Candales A Correlation of tricuspid lar velocities with invasive hemodynamics in pulmonary hypertension Congest Heart Fail 2007;13(4):200–4.

32 Tei C, Dujardin KS, Hodge DO, Bailey KR, McGoon MD, Tajik AJ, et al Doppler echocardiographic index for assessment of global right ventricular function J Am Soc Echocardiogr 1996;9:838–47.

36 Yoshifuku S, Otsuji Y, Takasaki K, Yuge K, Kisanuki A,

Toyo-naga K, et al Pseudonormalized Doppler total ejection

isovolume (Tei) index in patients with right ventricular

acute myocardial infarction Am J Cardiol 2003;91:527–31.

37 Vogel M, Schmidt MR, Kristiansen SB, et al Validation of

myocardial acceleration during isovolumic contraction as

41 Kittipovanonth M, Bellavia D, Chandrasekaran K, raga HR, Abraham TP, Pellikka PA Doppler myocardial imaging for early detection of right ventricular dysfunc- tion in patients with pulmonary hypertension J Am Soc Echocardiogr 2008;21(9):1035–41.

Villar-pumps and engage in functions of suction (relaxation)

and ejection (contraction) Relaxation aids in filling

during diastole, and therefore, filling parameters denote

diastolic function The phenomena of relaxation and

contraction are interlinked and energy-dependent

Diastole precedes systole, because no ejection is possible

unless there is filling first The processes of relaxation and

filling constitute diastolic function Increased resistance to

filling is the simplest way of defining diastolic dysfunction

Diastolic dysfunction is the first manifestation of a

disease process and explains the symptoms better

Abnormalities of diastolic function are common to

virtually all forms of cardiac disease Noninvasive

evaluation of diastolic ventricular function is based

on Doppler echocardiographic visualization of inflow

and/or ventricular tissue re-extension, although many

more parameters are described

The study of pressure–volume loop during diastole is

the ideal way to understand and assess diastolic function

However, there are several surrogate methods and

parameters in echo-Doppler techniques, which provide

reasonable, reliable and actionable information about

diastolic function In general, diastolic dysfunction may

be characterized by enlargement of upstream chamber

(atrium), alteration in various phases of diastole and

raised filling pressures However, diastolic dysfunction

is dynamic and in early phases, filling pressures are

provide enhanced information Diastolic compensatory mechanisms that maintain filling volume are the earliest evidence of dysfunction There is also evidence of regional diastolic wall motion nonuniformity Noninvasive surrogates often reported in clinical studies reflect integrative properties that lack specificity

Diastolic dysfunction is the physiological expression

of morphological cardiovascular disease The healthy myocardium is an active, nonlinear, nonhomogeneous and anisotropic viscoelastic material During diastolic lengthening, normal cardiac muscle behaves like a spring When the spring is more forcefully compressed during systole, diastolic lengthening is higher and vice versa (Fig 12.1)

There is a certain degree of systolic elastance and also

a definite degree of diastolic elastance.1 In several disease states like hypertension, diabetes and left ventricular hypertrophy as also with aging, systolic elastance remains unaffected or may actually increase, and diastolic elastance decreases, which can be studied and assessed by echo-Doppler parameters of diastolic function (Fig 12.2)

On the other hand, when systolic elastance is reduced, diastolic elastance initially increases due to remodeling and diastolic dysfunction denoted by filling pressures, therein, is a manifestation of fluid overload Most systemic

diseases affect the left ventricle (LV) primarily, and

therefore, it is pertinent to discuss largely about the left

ventricular diastolic function/dysfunction

• Decline of the myocardial active state following systole

• Passive effects of connective tissue

• Rapid changes in atrial and ventricular pressures

• Transmitral flow

• Interactions with the right ventricle and pericardium

• Atrial systole

• Identification of preclinical diseases in probands

• Diagnosis of clinical syndrome of heart failure

• Marker of incremental prognosis in diverse cardiac disorders

• Monitoring therapy and follow-up

• Understanding exercise physiology

• Cardiac versus noncardiac dyspnea

• Physiological versus pathological remodeling

• Optimizing devices and drugs response

• Evaluation of intraventricular dyssynchrony

• Study of pericardial diseasesThere is no single definition for diastolic dysfunction;

many features can get altered, and any one change

or their combination is typically called diastolic dysfunction, although the pathophysiology and functional significance varies greatly.2–4 Clinically, the most common manifestation is an elevated end-diastolic pressure and altered filling patterns, but neither of these identifies specific features of diastolic dysfunction (Fig 12.3)

When diastolic dysfunction is detected, it has some morphological, cellular and proteomic connotations These are:

• A change in the extracellular matrix of the myocardium, with the formation of excess collagen tissue5

• At the cellular level, there is reduced phosphorylation

of sarcomeric proteins

• At the proteomic level, an isoform change in important structural macromolecular proteins such as titin.6

Fig 12.1: Left ventricular pressure-volume loop Note that the diastole

is a mirror image of systole

(IVR: Isovolumic relaxation; IVC: Isovolumic contraction; RF: Rapid

filling; AS: Atrial systole).

Fig 12.2: Pressure-volume loop of a normal subject (green color) and that of a subject with diastolic dysfunction (red color) Note the same end-systolic elastance but with reduced end-diastolic elastance.

Fig 12.3: Diastolic dysfunction in clinical sense is raised diastolic

pressures, which means reduced compliance or increased diastolic

stiffness.

Diastole starts with closure of the aortic valve and ends

with onset of ventricular contraction (Fig 12.4) It has

an initial period of ventricular relaxation without filling

(isovolumic relaxation time [IVRT]) and then three phases

of ventricular filling (DFP) The four phases of diastole are:7

1 Isovolumic relaxation phase

2 Rapid filling phase

3 Diastasis

4 Late diastolic filling due to atrial contraction

Diastolic LV function can be assessed in each of the four

phases of diastole—isovolumic relaxation, rapid filling,

slow filling and atrial contraction (Fig 12.5) These four

phases uniquely reflect cardiomyocyte, myocardial or LV

physiology, and are invariably accessible to noninvasive evaluation Diastolic dysfunction is an abnormality that causes impaired relaxation (and decreased ventricular suction), poor filling or loss of atrial contraction.7

There are two phases in systole (Fig 12.6) These are:

1 Isovolumic contraction phase (IVC)

2 Ejection phase

Combined systolic and diastolic function can be assessed by the ratio of IVRT + IVC time/ejection time This ratio has been called myocardial performance index.8

Although used for prognosis in various diseased states,

it has not found practical utility for daily use in most echocardiography labs

Isovolumic relaxation time, which corresponds to the time interval from aortic valve closure to mitral valve opening,

is difficult to appreciate from simultaneous LV pressure, aortic pressure and wedge pressure recordings but is easily measured by continuous wave Doppler from the simultaneous display of the end of aortic ejection and the onset of mitral inflow (Fig 12.7)

IVRT has a predictable quantitative relationship to constant of isovolumic relaxation and to left atrial (LA) and aortic pressures.8

• Prolonged IVRT indicates poor myocardial relaxation

• A normal IVRT is about 70 ± 12 milliseconds, and approximately 10 milliseconds longer in people above

40 years of age

Fig 12.4: Graphical representation of various phases of the cardiac

cycle of the left heart.

(DFP: Diastolic filling period).

Fig 12.5: Continuous wave Doppler interrogation with sample volume placed between the left ventricular outflow and the inflow showing all four phases of diastole

(IVR: Isovolumic relaxation; RF: Rapid filling; diastasis—slow filling and AC—late filling due to atrial contribution).

Fig 12.6: Doppler signal from left ventricular inflow close to outflow

tract showing all phases of cardiac cycle

(ET: Ejection time; IVC: Isovolumic contraction).

• In abnormal relaxation, IVRT is usually in excess of

110 milliseconds

• With restrictive filling, it is usually under

60 milliseconds

• If IVRT is prolonged (> 110 milliseconds), LA pressure is

not elevated because the delay in mitral valve opening

is related to lower pressure crossover between LV and

LA in the setting of delayed relaxation

• It is safe to conclude that LA pressure is elevated if the

IVRT is short (< 60 milliseconds) in the presence of

cardiac disease

Its clinical value as an index of diastolic LV function

is limited, because it depends on mitral valve opening

pressures and, therefore, is not uniquely related to

LV dysfunction

In early diastole, chamber wall relaxation unmasks stored

elastic strain, allowing the LV to recoil and act as a suction

pump by aspirating blood into the ventricle Normal left

ventricular (LV) filling occurs rapidly early in diastole

caused by a progressive pressure gradient within the

ventricle and with a low LA pressure

Rapid filling phase accounts for 70% of left ventricular

filling It gets shorter in duration with raised filling

pressures and is prolonged in subjects with impaired

relaxation alone.9 When both impaired relaxation and

raised LA pressure coexist, it has variable duration like in

normal subjects Rapid filling phase is denoted by early diastolic (E) mitral flow wave and antegrade diastolic (D) flow wave of the pulmonary veins Variables affecting rapid filling phase are shown in Figure 12.8

WAVE (MItrAL E- And PuLMonArY d-WAVES)

Deceleration time (DT) is the duration between the peak

of early filling wave and where its linear descending slope reaches zero (Fig 12.9) Nonlinear slopes are not measured

Conditions associated with increased LV stiffness are associated with a more rapid rate of deceleration of early filling and a shorter time for this deceleration.10

• It is an index of resistance to early filling with normal values in range of 150–250 milliseconds

• DT denotes chamber stiffness regardless of heart rate, afterload and contractility

• DT of < 150 milliseconds indicates restrictive filling and relatively noncompliant LV (Fig 12.10)

• DT > 250 milliseconds indicates compensatory nism is in place to overcome impaired relaxation

mecha-Prolonging of DT during therapy is a positive sign

of recovery

• There is a close inverse relationship between DT and pulmonary wedge pressure

• DT is affected by age as well as pericardial restraint

As myocardial relaxation becomes less active with

Fig 12.7: Doppler interrogation between left ventricle outflow and

inflow showing measurement of isovolumic relaxation time (IVRT)

At heart rate of 66 beats/min, IVRT is 76 milliseconds in this normal

subject.

Fig 12.8: Variables affecting rapid filling phase in diastole

(PR: P wave to ORS wave interval).

aging or abnormally delayed due to a disease process,

the rate of LV pressure decline during the early diastole

is reduced, and it takes a longer time to reach the

minimal LV diastolic pressure

• Longer DT indicates impaired diastolic reserve

In this situation with abnormal myocardial relaxation,

a reduced diastolic filling period and a lack of atrial

contraction compromise LV filling

During the time of early flow deceleration, there is

rapid flow into the LA from the pulmonary veins DT of

pulmonary vein diastolic wave has same significance as

that of mitral DT (Fig 12.11) A pulmonary vein DT of < 150

milliseconds has much greater specificity for predicting

elevated filling pressures.11

During the slow LV filling phase or diastasis, residual effects of LV relaxation and ‘dynamic’ effects of fast LV inflow have dissipated This phase is used to construct diastolic LV pressure–volume relations from a single cardiac cycle and allows LV stiffness, the slope of the diastolic LV pressure–volume relation, to be derived under so-called static conditions In subjects with impaired relaxation and longer cardiac cycle, residual effects of LV relaxation may persist and positive filling wave during diastasis (L-wave) may be observed (Fig 12.12) Mitral valve L-waves may be evident in healthy patients with relatively low heart rates.12

Fig 12.9: Graphical display of deceleration time (DT) of mitral early

filling wave.

Fig 12.10: Restrictive filling pattern with deceleration time of

85 milliseconds in a patient with dilated cardiomyopathy.

Fig 12.11: Right upper pulmonary vein flow in a patient with atrial

fibrillation Measuring deceleration time of D-wave. Fig 12.12:(L-wave) during diastasis. Pulsed wave Doppler mitral flow showing positive wave

Importance of L-Wave

• The L-wave may be seen in relatively bradycardic

patients with normal hearts It is usually < 20 cm/s in

velocity

• A pathological L-wave typically is found in patients with

delayed active relaxation with increased LV stiffness

• In the echo laboratory, patients will often have clinical

heart failure, left ventricular hypertrophy with normal

systolic function or LV systolic dysfunction

• A pathological L-wave is suggestive of elevated

LV preload (pseudonormalization)

• A pathological L-wave has prognostic value, in that it is

predictive of future hospitalizations with heart failure

Occasionally, there can be negative L-wave or mid-diastolic mitral regurgitation due to rapid rise in

LV diastolic pressure as a consequence of early filling (Fig 12.13) Its exact significance is not clear

Late diastolic filling wave is of short duration and occurs due to atrial contraction just before systole starts This accounts for 20–40% of ventricular filling and is absent in atrial fibrillation This gets partly or completely obliterated

in first degree heart block and markedly raised ventricular stiffness Atrial kick is reflected by late diastolic (A) mitral flow wave and atrial flow reversal (Ar) in pulmonary veins

In markedly elevated left ventricular diastolic pressure, atrial contraction may not produce any antegrade flow wave and may be seen to send flow retrogradely in pulmonary veins (Fig 12.14)

dIAStoLIc FunctIon

As transmitral flow commences in diastole, the mitral annulus moves longitudinally upward toward the atrium Due to tissue and blood incompressibility, as the annulus rises, the wall thins, and the endocardium is simultaneously displaced radially outward toward the epicardium During filling, the short and long axes change simultaneously (Fig 12.15) Therefore, rate of longitudinal displacement and radial endocardial displacement are good indicators of diastolic function.13 Early diastolic longitudinal excursion rate can be easily obtained from tissue Doppler studies (Fig 12.16)

Fig 12.13: Mid-diastolic negative L-wave in a patient with left ventricular

diastolic dysfunction.

Fig 12.14: Monophasic mitral flow with normal PR interval and heart rate of 69 beats/min in a 90-year-old subject.

Fig 12.15: Graphical display of longitudinal and radial expansion of

the left ventricle during diastole (arrows).

The LV wall motion generates the atrioventricular

pressure gradient resulting in the early transmitral flow

(Doppler E-wave) and associated vortex formation

Substantial residual LV relaxation pressures in

mid-diastole present in some patients with stiff LV can

result in a positive wave called tissue L’-wave14 (Fig 12.17)

FunctIon/dYSFunctIon

The measurement of maximum LA volume is an essential

component of the comprehensive assessment of LV

diastolic function.15,16 More recently, LA volumes have

been obtained by 3D echocardiography

The LA volume is usually measured by biplane area–length method (Fig 12.18) In current guidelines, assessment of diastolic function mandates measurement

of LA volume index in every subject Although it has limited role in assessing diastolic function or dysfunction

in acute situations, it has great relevance in chronic stable cardiovascular conditions

• The LA volume can be viewed as a morphological expression of LV diastolic dysfunction

• Left atrial volume is regarded as a ‘barometer’ of the chronicity of diastolic dysfunction

• This simple measure of LA volume provides significant insight into an individual’s risk for the development of adverse cardiovascular events, including myocardial infarction, stroke, atrial fibrillation and heart failure

• Normal values for LA volume are 22 ± 6 mL/M2

• Left atrial volume is graded relative to risk, 28–33 mL/

M2 = mild; 34–39 mL/M2 = moderate; and ≥ 40 mL/M2

regur-Fig 12.16: Biphasic longitudinal expansion of the left ventricle

during diastole E’, early diastolic and A’, late diastolic longitudinal

tis-sue velocity waves.

Fig 12.17: Tissue L’-wave in diastasis (arrow).

Fig 12.18: Estimation of biplane end-systolic left atrial volume by

area–length method.

• There is a fairly good positive correlation between

LA volume index and grade of diastolic dysfunction

• Maximum LA systolic lengthening and its rate have

also been found to correlate with diastolic dysfunction

(Figs 12.19 and 12.20)

• It is possible to use LA strain during ventricular

systole along with LA pressure or its Doppler

echocardiographic surrogate (E/e′) to calculate

LA chamber stiffness.17

• LA stiffness has good accuracy in identifying patients

in diastolic heart failure

• Change in volume–pressure relationships in left atrium

also indicates change in material properties (ischemia,

fibrosis, etc.) and physiological or pathological remo deling in the LV

Factors extrinsic to the left ventricular myocardium may influence the end-diastolic pressure–volume relationship Changes in intrathoracic pressure (as with spontaneous or assisted ventilation), pericardial constraints and interventricular interactions may each influence ventricular diastolic pressure (when referenced

to atmospheric pressure), which therefore influences this relationship In the absence of these, intrinsic diastolic function governs this relationship Various equations have been derived from mitral flow and tissue expansion rate to predict end-diastolic pressure E/e’ ratio has the strongest relation to pulmonary capillary wedge pressure (PCWP) [r = 0.86, PCWP = 1.55 + 1.47(E/Ea)], irrespective of the pattern and ejection fraction.18

on dIAStoLIc FunctIon

• After estimation of biplane LA volume, one proceeds

to interrogate by pulsed wave (PW) Doppler, four different sites as shown in Figure 12.21

• With the patient supine, apical four-chamber views using a 2.5-MHz transducer are obtained with the sample volume gated at 1.5–5 mm directed between the tips of the mitral valve leaflets and orthogonal to the mitral valve plane

• Continuous wave Doppler is used to record aortic outflow and mitral inflow from the apical view for determination of the IVRT using a sweep speed of

100 mm/s

Fig 12.19: Left atrial (LA) longitudinal lengthening in a normal

subject compared to that of the left ventricle shortening Typically, LA

lengthening is twice or more than that of the LV shortening.

Fig 12.20: Significantly reduced left atrial global strain in the presence

of diastolic dysfunction.

Fig 12.21: Sites for assessing diastolic function in an apical

four-chamber view.

• In apical four-chamber view, ostium of the right upper

pulmonary vein is interrogated by PW Doppler

• M-mode of the color flow propagation velocity across

the mitral valve up to 4 cm into the cavity is obtained

• Doppler tissue imaging (DTI) of the medial and the

lateral mitral annulus and M-mode images are also

recorded DTI is performed at a sample size gated at

2.5 mm

• Effect of Valsalva maneuver is also observed for the

mitral and pulmonary vein flow

• Sometimes, supine exercise is used to study diastolic

function parameters Post exercise E/A ratio as an

independent determinant of severity of exercise

induced dyspnea and impaired exercise tolerance

• Longitudinal strain and untwisting rate of the LV are

also recorded by acoustic speckle tracking

• After obtaining all the measurements, the diastolic

dysfunction, if present, is graded and occasionally it

may be noted as indeterminate if multiparameters give

conflicting results

The mitral inflow velocity profile is initially used to

characterize LV filling dynamics (Fig 12.22)

• E velocity (E) represents the early mitral inflow velocity

and is influenced by the relative pressures between the

LA and LV, which, in turn, are dependent on multiple

variables including LA pressure, LV compliance and

the rate of LV relaxation.19

• A velocity (A) represents the atrial contractile component of mitral filling and is primarily influenced

by LV compliance and LA contractility

• The DT of the E velocity is the interval from peak E to

a point of intersection of the deceleration of flow with the baseline and it correlates with time of pressure equalization between the LA and LV Incomplete or delayed relaxation causes a delay in the transfer of blood from atria to ventricle

• As the early LA and LV filling pressures either evolve toward or away from equivalence, so will the DT either shorten or lengthen, respectively

• Diastolic dysfunction is directly related to the reduction

in early LV relaxation compromising the effective transfer of the blood from the atrial reservoir into the

LV cavity

• Diastolic dysfunction can be categorized into three stages based upon transmitral filling patterns.2–4

Grade I: Impaired relaxation denoted by DT > 250

milliseconds and E/A velocity ratio < 0.8 (Figs 12.23 and 12.24) The American Society of Echocardiography(ASE) and European Association of Echocardiography (EAE) guidelines suggest DT > 200 milliseconds in Grade I

Early in the evolution of ‘diastolic dysfunction’, the delay in emptying (DT > 250 milliseconds) is partially compensated by a more vigorous end-diastolic atria contraction, and, therefore, the E/A ratio is reduced (< 0.8)

Grade II: Pseudonormal pattern with DT of 150–250

milliseconds and E/A ratio between 0.8 and 1.5 ASE–EAE guidelines put DT in range of 160–200 milliseconds

Fig 12.22: Biphasic mitral flow with sample volume at the tips of the

mitral leaflets. Fig 12.23:prolonged deceleration time. Grade I diastolic dysfunction in transmitral flow with

Pseudonormal pattern needs confirmation by

increased LA volume (> 34 mL/M2) or mitral E-wave

velocity/annular tissue early diastolic velocity > 15

(medial) or > 12 (lateral) or pulmonary vein flow increased

duration of atrial flow reversal wave or Valsalva maneuver

to unearth impaired relaxation in mitral flow

Presence of L-wave or DT < 150 milliseconds could

also provide clue to pseudonormal pattern if E/A velocity

ratio is 0.8–1.5

Grade III: Restrictive flow or reduced compliance

pattern with DT < 160 milliseconds and E/A ratio ≥ 2.0

Others have used DT cut-off limits of < 150 milliseconds

and < 130 milliseconds as well

Mitral Inflow Measurements

Following measurements should be made in each

examination:

• Peak early filling (E-wave)

• Late diastolic filling (A-wave) velocities

• Diastolic filling time

• A-wave velocity–time integral

• Total mitral inflow velocity–time integral (and thus the

atrial filling fraction) with the sample volume at the

level of the mitral annulus

• Mid-diastolic flow is an important signal to recognize

Low velocities can occur in normal subjects, but when increased (≥ 20 cm/s), they often represent markedly delayed LV relaxation and elevated filling pressures

Most confusions arise in so-called pseudonormal pattern, wherein one or the other parameter can be discordant (Fig 12.25) Help can be obtained from using multiple parameters and any of the other abnormality could be construed as abnormal diastolic function especially if the early diastolic annular tissue velocity is significantly reduced.3,4

Restrictive flow is relatively easy to detect and is unambiguous in adult patients with heart disease (Fig 12.26).20 These criteria can not be used in children and young adults who normally have large E-waves and short DT due to very active suction of the LV

Although not supported by the ASE, others have used Grade IV diastolic dysfunction as the one in which either the restrictive pattern is irreversible21 or has monophasic flow pattern with absent A-wave despite sinus rhythm, normal PR interval and usual heart rates (Fig 12.27)

Mitral Inflow: Acquisition and Feasibility

• PW Doppler is performed in the apical four-chamber view to obtain mitral inflow velocities to assess

LV filling

• Color flow imaging can be helpful for optimal alignment of the Doppler beam, particularly when the

LV is dilated

• Performing continuous wave Doppler to assess peak E

Fig 12.24: Grade I diastolic dysfunction denoted by deceleration time

of 278 milliseconds and E/A 0.7.

Fig 12.25: Pseudonormal or Grade II diastolic dysfunction denoted by presence of L-wave (arrow).

(early diastolic) and A (late diastolic) velocities should

be performed before applying the PW technique to

ensure that maximal velocities are obtained

• A 1- to 3-mm sample volume is then placed between

the mitral leaflet tips during diastole to record a crisp

velocity profile

• Optimizing spectral gain and wall filter settings is

important to clearly display the onset and cessation of

LV inflow

• Spectral mitral velocity recordings should be initially

obtained at sweep speeds of 25–50 mm/s for the

evaluation of respiratory variation of flow velocities, as seen in patients with pulmonary or pericardial disease

• If variation is not present, the sweep speed is increased

to 100 mm/s, at end-expiration, and averaged over three consecutive cardiac cycles

• The Valsalva maneuver is performed by forceful expiration (approximately 40 mm Hg) against a closed nose and mouth, producing a complex hemodynamic process involving four phases It helps to identify pseudonormal mitral inflow and irreversible restrictive flow A decrease in E/A ratio ≥ 0.5 is the criterion (Figs 12.28 and 12.29)

In cardiac patients, a decrease of ≥ 50% in the E/A ratio during Valsalva maneuver is highly specific for increased LV filling pressures, but a smaller magnitude of change does not always indicate normal diastolic function

No change in restrictive flow is an ominous sign.21

Diastolic tissue velocities measured at the mitral annulus show low-velocity deflections during early filling (e′) and with atrial contraction (a′) with great clarity.22,23 These indicate biphasic longitudinal expansion rate of the LV (Fig 12.30)

• e′ is presumed to correlate closely with LV relaxation indexes and to be relatively preload insensitive

• Similar to mitral E flow, e′ appears to be age-dependent

Fig 12.26: Restrictive (Grade III) flow pattern with short deceleration

time and E/A ratio ≥ 2.

Fig 12.27: Monophasic transmitral flow pattern in a patient with advanced diastolic dysfunction and heart failure due to previous anterior wall myocardial infarction.

Fig 12.28: Valsalva maneuver changing restrictive flow pattern

(left panel) to pattern of impaired relaxation (right panel).

Fig 12.29: Effect of Valsalva Upper panel shows restrictive flow

pattern, which changes to pseudonormal pattern with an L-wave at the

end of Valsalva maneuver.

Fig 12.30: Annular tissue velocities from lateral edge of the mitral annulus See text for description.

• E depends on LA pressure, residual LV relaxation

pressure and age and because e′ is presumed to

depend only on LV relaxation pressure, dividing E by e′

eliminates LV relaxation pressure and age, so the E/e′

ratio becomes a noninvasive estimate of LA pressure

(Fig 12.31)

• Septal and lateral mitral annular e′ velocities differ

Recent guidelines for the detection of diastolic

dysfunction recommend use of an E/e′ value that is the

average of septal and lateral mitral annular e′

• A value of medial E/e′ > 15 is usually proposed as evidence for elevated LV filling pressure and a value of E/e′ < 8 as evidence for normal LV filling pressure

• There is a wide range of E/e′ values9–12 for which additional investigations are required to obtain a LV filling pressure estimate (Fig 12.32)

• Technical limitations include angle dependency, signal noise, signal drifting, spatial resolution, sample volume and tethering artifacts

Fig 12.31: Upper panel shows mitral inflow pattern and the lower

panel depicts annular velocities from the lateral edge of the mitral

annulus An E/e’ of 7 indicates normal diastolic function as the e’ is

10 cm/s.

Fig 12.32: Upper panel shows restrictive transmitral flow and the lower panel shows annular velocities of septal edge of the mitral annulus An E/e’ ratio of 10 falls in indeterminate zone.

• e′ can be decreased erroneously by mitral annular

calcification, surgical rings or prosthetic valves

• An average of septal and lateral E/e’ ≥ 13 is suggestive

of elevated filling pressures

• A reduced s’ velocity is an indirect index of diastolic

dysfunction, because there is a close correlation

between longitudinal systolic function and early

diastolic function

• In healthy young individuals, septal e′ is ≥ 10 cm/s

and lateral e′ ≥ 15 cm/s at rest But there are

vendor-dependent variations

• e’ < 5 cm/s in cardiac disease is reflection of advanced

diastolic dysfunction

• E/e′ may not work well in patients with severe mitral

regurgitation, intraventricular conduction delay, or

pacemaker

tISSuE VELocItIES

• PW Doppler tissue imaging is performed in the apical

views to acquire mitral annular velocities

• The sample volume should be positioned at or 1 cm

within the septal and lateral insertion sites of the mitral

leaflets

• It is recommended that spectral recordings be obtained

at a sweep speed of 50–100 mm/s at end-expiration

and that measurements should reflect the average of

three or more consecutive cardiac cycles

• Primary measurements include the systolic (s), early

(é) and late (á) diastolic velocities

• For the assessment of global LV diastolic function, it is recommended to acquire and measure tissue Doppler signals at least at the septal and lateral sides of the mitral annulus and their average

• In patients with cardiac disease, é can be used to correct for the effect of LV relaxation on mitral E velocity, and the E/é ratio can be applied for the prediction of LV filling pressures

• The E/é ratio is not accurate as an index of filling pressures in normal subjects or in patients with heavy annular calcification, mitral valve disease and constrictive pericarditis

• Presence of tissue Doppler wave during diastasis (l’) is suggestive of diastolic dysfunction (Fig 12.33)

• Higher accuracy of a single-cycle E/e′ ratio in predicting mean wedge pressure in patients with atrial fibrillation using a dual Doppler echocardiographic probe has been shown

• Strain rate during IVRT has good correlations with the time constant of LV relaxation and −dP/dt and is not affected by changes in preload Strain rate can be obtained by tissue velocity imaging.24

Practical tips

• In the presence of normal or pseudonormal mitral flow pattern, an E/e’ ratio ≥ 15 obtained from either edge of the mitral annulus suggests Grade II diastolic dysfunction (Fig 12.34)

• In long-standing disease, an E/e’ ratio may not accurately reflect the magnitude of filling pressures but may be indicative of stiff LV (Fig 12.35)

Fig 12.33: Lateral edge mitral annular velocities showing l’ (arrow)

Diastolic dysfunction is also suggested by e’ < a’.

Fig 12.34: Upper panel shows mitral E of 130 cm/s and the lower panel shows septal edge e’ of 7 cm/s E/e’ ratio is 19, indicating Grade II diastolic dysfunction.

• Greater utility of E/e’ lies in patients with systolic

dysfunction as compared to those with pure diastolic

dysfunction

• In relatively younger patients, this ratio has greater

predictive value for filling pressure and symptoms

(Figs 12.36 and 12.37)

• If E/e’ does not clearly indicate presence of diastolic

dysfunction, an e’/a’ ratio < 1 can be used along with

other data (Fig 12.38)

• In elderly people, all normal-appearing mitral flow

patterns can not be regarded as pseudonormal

An E/e’ may help define the degree of normalcy

(Fig 12.39)

• Fusion of mitral E- and A-waves may make E/e’ calculation difficult (Fig 12.40) Fusion occurs in several conditions listed below

– Sinus tachycardia– Prolonged PR interval– Intraventricular dyssynchrony– Advanced diastolic dysfunction

• In many disease states, post-systolic tissue waves may mask tissue e’, making it difficult to estimate E/e’ ratio (Fig 12.41)

• Annular post-systolic positive waves may convert severe diastolic dysfunction to mild by virtue of changing transmitral flow pattern (Fig 12.42)

Fig 12.35: Upper panel shows transmitral flow, while the lower

panel shows annular velocities at the septal edge in a patient on

maintenance hemodialysis An E/e’ ratio of 34 does not necessarily

imply very high filling pressures in this otherwise stable patient.

Fig 12.36: Left panel shows normal transmitral flow, while mitral annular velocity at septal margin is 5 cm/s and E/e’ ratio of 20 is indicative of elevated filling pressures and most likely cause of dyspnea.

Fig 12.37: Same patient as in Figure 12.36 E/e’ at lateral margin of

the mitral annulus (16.5) is lower than that at the septal margin but

is still way above normal A lateral E/e’ ≥ 12 is indicative of diastolic

dysfunction.

Fig 12.38: An indeterminate E/e’ ratio from the septal edge is mented by absolute e’ of 5 cm/s and e’/a ratio < 1 in suggesting diastolic dysfunction.

compli-Fig 12.39: A 70-year-old healthy woman with normal mitral flow and

a septal edge E/e’ of 11.

Fig 12.40: Improbability of estimating E/e’ ratio due to fusion of mitral E and A in presence of sinus tachycardia and absence of annular e’-wave (upper panel).

Fig 12.41: Post-systolic annular tissue wave masking e’ This could

be called reversed e’.

Fig 12.42: Impaired relaxation pattern of mitral flow (upper panel)

in a patient with advanced heart failure Post-systolic annular waves extending into mid-diastole (lower panel).

• An E/e’ ratio may not be reliable in the presence of

atrial fibrillation, sinus bradycardia and first degree AV

block (Fig 12.43)

• LV diastolic function can be deciphered through

the evaluation not only of the relationship of the

amplitude of E to e′ but also through the evaluation of

the relationship of the timing of the onset of E to the

onset of e′ Normally, mitral inflow is initiated with

rapid LV relaxation and ‘suction’ of blood into the LV

When this occurs, the onset of e′ will be slightly before

or simultaneous with the onset of E.25 If, however,

LA pressure is elevated and LV relaxation reduced, E

velocity onset may precede the onset of e′ (Fig 12.44) These timing relationships have been correlated with

to 12.47) First S-wave is due to atrial relaxation and the

Fig 12.43: E/e’ ratio of 7 (lateral) in an 84-year-old person with sinus

bradycardia, first degree AV block with heart failure.

Fig 12.44: Mitral E preceding tissue e’ in a patient with Grade II tolic dysfunction.

dias-Fig 12.45: Pulmonary vein flow pattern in a normal subject Patients

with Grade I diastolic dysfunction have similar pattern.

Fig 12.46: Equivalent pulmonary systolic and diastolic wave but with prolonged atrial flow reversal (Ar) suggestive of diastolic dysfunction.

Fig 12.47: Graphical representation of pulmonary vein flow in a

subject with raised left ventricle filling pressure.

second one (S2) due to descent of the mitral annulus during systole D-wave occurs during opened mitral valve

Ar-wave occurs following atrial contraction when blood has option of flowing antegradely into the LV as well as back in pulmonary veins depending upon the relative resistance.26

• The pattern of pulmonary venous flow (systolic vs

diastolic predominance) has been proposed as a dictor of diastolic dysfunction (Figs 12.48 and 12.49)

pre-However, diastolic preponderance is invariable in children and young adults

• Ar velocity > 35 cm/s also indicates raised filling pressures (Fig 12.49)

• Comparison of the duration of flow at atrial contraction across the mitral valve (on the mitral inflow velocity curve) and the duration of reversal flow back into the pulmonary veins (on the pulmonary venous velocity

Fig 12.48: Right upper pulmonary vein diastolic flow velocity and

velocity–time integral is greater than systolic filling fraction in a patient

with significant diastolic dysfunction.

Fig 12.49: Right upper pulmonary vein atrial flow reversal (Ar) velocity

of 50 cm/s indicative of diastolic dysfunction.

Fig 12.50: Atrial flow reversal (Ar) duration of pulmonary vein > mitral

A by > 30 milliseconds is suggestive of elevated LV end-diastolic

curves) has been repeatedly demonstrated to reflect

the left ventricular end-diastolic pressure (Fig 12.50)

• If the duration of atrial reversal flow in the pulmonary

vein exceeds by more than 30 milliseconds the duration

of flow across the mitral valve, raised left ventricular

end-diastolic pressure can be diagnosed with high

specificity

• The major limitations to the use of the pulmonary

venous signals are that these signals are difficult

to obtain and interpret The technical feasibility of

obtaining adequate signals has been reported at < 80%

of unselected patients

• Pulmonary vein flow, when interpretable, is used to refining the grades of diastolic dysfunction (Figs 12.51

to 12.53)

• Longer duration of mitral atrial flow compared to that

of pulmonary vein atrial flow reversal velocity may

be found in Grade I diastolic dysfunction besides in normal subjects

Acquisition of Pulmonary Vein Flow Signals

• Color flow imaging is useful for the proper location of the sample volume in the right upper pulmonary vein

Fig 12.52: Equivalent pulmonary venous systolic and diastolic flow

fraction (lower panel) but with inspiratory decrease in D-wave (arrow)

is suggestive of normal filling pattern.

Fig 12.53: Upper panel: mitral flow, middle panel: pulmonary flow, lower panel: septal annular velocities There is hardly any S-wave in pulmonary vein flow and E/e’ of 30 indicating advanced diastolic dys- function.

• In most patients, the best Doppler recordings are

obtained by angulating the transducer superiorly such

that the aortic valve is seen

• A 2- to 3-mm sample volume is placed > 0.5 cm into the

pulmonary vein for optimal recording of the spectral

waveforms

• Wall filter settings must be low enough to display the

onset and cessation of the Ar velocity waveform

• Pulmonary venous flow can be obtained in > 80% of

ambulatory patients, although the feasibility is much

lower in the intensive care unit setting

• The major technical problem is LA wall-motion

artifacts, caused by atrial contraction, which interferes

with the accurate display of Ar velocity

• Spectral recordings should be obtained at a sweep

speed of 50–100 mm/s at end-expiration and

measurements include the average of three or more

consecutive cardiac cycles

Pulmonary Vein Flow Parameters

• Measurements of pulmonary venous waveforms

include peak systolic (S) velocity, peak anterograde

diastolic (D) velocity, the S/D ratio, systolic and

diastolic filling fractions, and the peak Ar velocity in

late diastole

• Other measurements are the duration of the Ar

velocity, the time difference between it and mitral

A-wave duration (Ar−A)

• D velocity DT There are two systolic velocities (S1

and S2), mostly noticeable when there is a prolonged

PR interval, because S1 is related to atrial relaxation

S2 should be used to compute the ratio of peak systolic

to peak diastolic velocity

• S1 velocity is primarily influenced by changes in LA pressure and LA contraction and relaxation, whereas S2 is related to stroke volume and PW propagation in the pulmonary arterial tree

• D velocity is influenced by changes in LV filling and compliance and changes in parallel with mitral

E velocity

• Pulmonary venous Ar velocity and duration are influenced by LV late diastolic pressures, atrial preload and LA contractility

• A decrease in LA compliance and an increase in LA pressure decrease the S velocity and increase the

D velocity, resulting in an S/D ratio < 1, systolic filling fraction < 40% and shortening of the DT of D velocity, usually < 150 milliseconds (Figs 12.54 and 12.55)

• However, DT of mitral E and pulmonary vein D may not always be concordant as DT of D-wave tends to be nonlinear more often (Fig 12.56)

coLor M-ModE

Assessment of flow propagation into the LV is another technique that provides better ability to predict filling pressures.27,28

In the normal state, flow rapidly propagates into the

LV (Fig 12.57) Early stage relaxation abnormalities show

a blunting of flow propagation

The propagation velocity (Vp) does not show a

pseudonormalization, and therefore, can be used in all

levels of diastolic dysfunction

Similar to the tissue Doppler velocities, color M-mode

flow propagation has been combined in a ratio with the

mitral E velocity to provide an ‘adjusted’ parameter (E/Vp)

with strong correlation to filling pressures and prognosis

The chief limitations of this tool are lack of consensus

on technique and theoretical concerns that this will be

invalid in small left ventricular cavities

Practical tips

• Acquisition is performed in the apical four-chamber view, using color-flow imaging

• M-mode scan line is placed through the center of the

LV inflow blood column from the mitral valve to the apex, with baseline shift to lower the Nyquist limit so that the central highest velocity jet is blue

• Vp is measured as the slope of the first aliasing velocity during early filling, measured from the mitral valve

Fig 12.54: Upper panel: pulmonary vein flow, lower panel:

transmi-tral flow Restrictive transmitransmi-tral flow is negated by normal pulmonary

venous flow, although atrial flow reversal is 20 milliseconds longer.

Fig 12.55: Pulmonary vein D-wave > S-wave with deceleration time

of 130 milliseconds indicating elevated left ventricular filling pressure.

Fig 12.56: Upper panel shows short deceleration time (DT) of mitral

E, while DT of pulmonary vein D is longer (170 milliseconds) and

non-linear.

Fig 12.57: Mitral flow propagation velocity by M-mode.

plane to 4 cm distally into the LV cavity, or the slope of

the transition from no color to color

• Vp > 45–50 cm/s is considered normal (Fig 12.58)

• Should other Doppler indices appear inconclusive,

an E/Vp ratio ≥ 2.5 predicts PCWP > 15 mm Hg with

reasonable accuracy (Fig 12.59)

• Patients with normal LV volumes and EFs but elevated

filling pressures can have misleadingly normal Vp

• Peak velocity of early diastolic mitral flow propagation

velocity (Vp) has been used as an approximation for

ventricular suction

untWIStInG rAtE BY AcouStIc SPEcKLE trAcKInG

• Most patients with diastolic dysfunction have impaired longitudinal strain by acoustic speckle tracking Impaired longitudinal strain (> –15%) is the first indi-cation of impaired diastolic function.29

• Torsion and circumferential strain are normal in patients with isolated diastolic dysfunction (Fig 12.60)

• Assessment of LV torsion has shown that untwisting begins before aortic valve closure and might be an important component of normal diastolic filling.28

• Studies in human subjects using indirect indexes derived from right heart catheterization have suggested a relationship between constant of isovolumic relaxa tion and measures of untwisting

• But the relationship between directly measured diastolic function indexes with micromanometer catheters and untwisting parameters has not been established in human subjects

• Untwisting parameters are related to invasive indexes

of LV relaxation and suction but not to LV stiffness

These data suggest that untwisting is an important component of early diastolic LV filling but not of later diastolic events

Fig 12.58: Vp of 31 cm/s in a patient with heart failure. Fig 12.59: A 43-year-old female with recurrent pulmonary edema

E/e’ of 12.5 (lateral) is inconclusive but E/Vp of 3.3 suggests raised filling pressures.

Fig 12.60: Normal circumferential strain (right panel) in presence of

advanced diastolic dysfunction.

ˆ dIAStoLIc StrESS tESt

Many patients present with exertional dyspnea but have

normal LV filling pressures at rest

In these patients, it is important to evaluate filling

pressure with exercise.30,31

Exercise can be performed using a supine bicycle or

treadmill protocol

Fig 12.61: Diastolic stress test in a normal person There is proportionate increase in mitral E and e’.

Because most patients have limited functional capacity, the workload starts at 25 W and increases in increments of

25 W every 3 minutes

We need to record mitral inflow by pulsed Doppler echocardiography at the level of the mitral tips, mitral annular velocities by spectral Doppler echocardiography and tricuspid regurgitation jet by CW Doppler (Fig 12.61)

Doppler echocardiography provides major insights into the pathophysiology of diastolic LV dysfunction So far, however, no single Doppler echocardiographic index of diastolic LV dysfunction has yielded a robust criterion for elevated LV filling pressures A stepwise strategy with sequential use of multiple Doppler echocardiographic indexes reduces diagnostic sensitivity because it frequently leads to an indeterminate outcome A multiparametric approach with age and clinical situation in mind is the best way of using echocardiography in detection of diastolic dysfunction because it is so complex and dependent upon multitude of variables (Fig 12.62) Because of these persistent shortcomings, clinicians should continue to make critical use of current Doppler echocardiographic estimates of LV filling pressures and should not hesitate

to implement invasive investigations to confirm their

Fig 12.62: A simplified schema to report diastolic function based upon

pulsed wave Doppler mitral flow, annular velocities and pulmonary

vein flow

(DTI: Doppler tissue imaging).

left ventricular end-diastolic pressure volume loop

esti-mate predicts survival in congestive heart failure J Card

Fail 2013;19(4):251–9.

2 Nagueh SF, Appleton CP, Gillebert TC, et al

Recommenda-tions for the evaluation of left ventricular diastolic function

by echocardiography Eur J Echocardiogr 2009;10:165–93.

3 Chapman CB, Ewer SM, Kelly AF, et al Classification of left

ventricular diastolic function using american society of

echocardiography guidelines: agreement among

echocar-diographers Echocardiography 2013;30(9):1022-31.

4 Dokainish H, Nguyen JS, Bobek J, et al Assessment of

the American Society of Echocardiography-European

Association of Echocardiography guidelines for diastolic

function in patients with depressed ejection fraction: an

echocardiographic and invasive haemodynamic study Eur

J Echocardiogr 2011;12(11):857–64.

5 Martos R, Baugh J, Ledwidge M, et al Diastolic heart failure:

evidence of increased myocardial collagen turnover linked

to diastolic dysfunction Circulation 2007;115(7):888–95.

6 Granzier HL, Labeit S The giant protein titin: a major player

in myocardial mechanics, signaling, and disease Circ Res

2004;94(3):284–95.

7 Gillebert TC, De Pauw M, Timmermans F Echo-Doppler

assessment of diastole: flow, function and

haemodynam-ics Heart 2013;99(1):55–64.

8 Oh JK, Tajik J The return of cardiac time intervals: the

phoe-nix is rising J Am Coll Cardiol 2003;42(8):1471–4.

9 Nishimura RA, Appleton CP, Redfield MM, et al

Noninvasive doppler echocardiographic evaluation of left

ventricular filling pressures in patients with

cardiomyo-pathies: a simultaneous Doppler echocardiographic and

cardiac catheterization study J Am Coll Cardiol 1996;28(5):

1226–33.

10 Little WC, Ohno M, Kitzman DW, et al Determination of

left ventricular chamber stiffness from the time for

deceler-ation of early left ventricular filling Circuldeceler-ation 1995;92(7):

1933–9.

11 Rossvoll O, Hatle LK Pulmonary venous flow velocities

recorded by transthoracic Doppler ultrasound: relation

to left ventricular diastolic pressures J Am Coll Cardiol

17 Khan UA, de Simone G, Hill J, et al Depressed atrial tion in diastolic dysfunction: a speckle tracking imaging study Echocardiography 2013;30(3):309–16.

18 Nagueh SF, Middleton KJ, Kopelen HA, et al Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures

J Am Coll Cardiol 1997;30(6):1527–33.

19 Nishimura RA, Tajik AJ Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiog- raphy is the clinician’s Rosetta Stone J Am Coll Cardiol

1997;30(1):8–18.

20 Kitabatake A, Inoue M, Asao M Transmitral blood flow reflecting diastolic behavior of the left ventricle in health and disease–a study by pulsed Doppler technique Jpn Circ

J 1982;46:92–102.

21 Pinamonti B, Zecchin M, Di Lenarda A, et al Persistence

of restrictive left ventricular filling pattern in dilated cardiomyopathy: an ominous prognostic sign J Am Coll Cardiol 1997;29(3):604–12.

22 Ommen SR, Nishimura RA, Appleton CP, et al Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheteri- zation study Circulation 2000;102(15):1788–94.

23 Oki T, Tabata T, Yamada H, et al Clinical application of pulsed Doppler tissue imaging for assessing abnormal left ventricular relaxation Am J Cardiol 1997;79:921–8.

24 Wang J, Khoury DS, Thohan V, et al Global diastolic strain rate for the assessment of left ventricular relaxation and filling pressures Circulation 2007;115(11):1376–83.

25 Rivas-Gotz C, Khoury DS, Manolios M, et al Time interval between onset of mitral inflow and onset of early diastolic velocity by tissue Doppler: a novel index of left ventricular relaxation: experimental studies and clinical application

J Am Coll Cardiol 2003;42(8):1463–70.

Muscle Mechanics

Chapters

Ö Tissue Doppler Echocardiography: Current Status

and Applications

Ö Deformation Imaging: Theory and Practice

Ö Rotation, Twist and Torsion