Two-Dimensional and Doppler Evaluation of Left Ventricular Filling, Including Pulmonary Venous Flow Velocity

Abbreviations

2-D

two-dimensional (echo)

A-fib

atrial fibrillation

A-wave

flow velocity due to atrial contraction

BPM

beats per minute

CMM

color M-mode (Doppler)

CV

cardiovascular

CW Doppler

continuous wave Doppler (technique)

DHF

diastolic heart failure

E-wave

ventricular inflow velocity in early diastole

HF

heart failure

HFpEF

heart failure with preserved ejection fraction

HFrEF

heart failure with reduced ejection fraction

HT

hypertension

HV

hepatic vein

IR

impaired relaxation (LV filling)

IVRT

isovolumic relaxation time

LA

left atrial

LBBB

left bundle branch block

LV

left ventricular

LVEF

LV ejection fraction

LV EDP

LV end-diastolic pressure

LVOT

LV outflow tract

LA A-wave

LV pressure rise due to atrial contraction

LVH

LV hypertrophy

MAM

mitral annular motion

Mitral Adur

duration if mitral A-wave velocity

Mitral DT

mitral deceleration time

MR

mitral regurgitation

MS

mitral stenosis

PA

pulmonary artery

PN

pseudonormal (LV filling)

Pre-A

mitral velocity or LV pressure at the start of atrial contraction

PV

pulmonary venous

PVd

pulmonary venous diastolic flow velocity

PVs

pulmonary venous systolic flow velocity

PVs1

PV flow velocity in early systole

PVs2

PV flow velocity in middle and late systole

PVa

reverse pulmonary flow at atrial contraction

PV Adur

reverse PV flow velocity at atrial contraction

PW Doppler

pulsed-wave Doppler (technique)

RST

restrictive (LV filling)

RV

right ventricular

SHF

systolic heart failure

TDI

tissue Doppler imaging

TMPG

transmitral pressure gradient

TR

tricuspid regurgitation

Introduction

The cardiac cycle is continuous. The filling of the ventricle (diastole) is followed by ventricular contraction (systole) to provide an adequate cardiac output during both rest and exercise to meet the body’s metabolic demands. Both systole and diastole affect each other in an intimate manner to accomplish this goal. The normal elastic recoil after left ventricular (LV) contraction aids early filling of the ventricle with the late diastolic atrial contraction ensuring that the myocardial sarcomeres are adequately stretched to optimize contractile force. Exercise tests the health of this integrated system by shortening the time for filling and myocardial perfusion, and a normally functioning cardiac electrical system is also needed for optimal performance.

Systole and diastole are inextricably linked, with ventricular contraction compressing elastic elements whose recoil augments early diastolic filling.
This interrelation helps ensure adequate diastolic time for cardiac filling and myocardial perfusion.
Loading conditions, inotropic stimulation, and neurohumoral factors generally affect both systolic and diastolic function in parallel fashion.

The so-called new epidemiology of LV diastolic dysfunction has been discussed in Chapter 7 . Diastolic heart failure or heart failure with preserved ejection fraction (HFpEF) is now recognized as a major national health problem, especially in the elderly who have a high incidence of LV hypertrophy (LVH). These patients present with symptomatic heart failure (HF) despite a normal LV ejection fraction (LVEF) and have morbidity and mortality nearly equal to that of patients with reduced systolic function. They are also at risk for first onset atrial fibrillation and a higher incidence of stroke. Although the LVEF is normal in HFpEF, ventricular contractile mechanics have been altered in a way that lengthens the isovolumic contraction and relaxation period so that the period for diastolic filling becomes shorter and may be inadequate. With both heart failure with reduced ejection fraction (HFrEF) and HFpEF the degree of diastolic dysfunction is a powerful predictor of prognosis.

Despite this new appreciation of the importance of both systole and diastole in maintaining normal cardiovascular (CV) physiology, the role of LV diastolic function in health and disease is incompletely understood and underappreciated by many primary care physicians and cardiologists. As discussed in 1, 2, 3, 4, 5, 6 , diastole is a complex phenomenon with many determinants that are difficult to study individually and with several phases that encompass both the relaxation and then filling of the ventricle. Physical examination, electrocardiogram (ECG), chest radiographs, and laboratory studies are unreliable in diagnosing diastolic HF in many individuals, and invasive measurements of LV diastolic properties and pressures are impractical in clinical practice. Therefore, at present, assessing the type and degree of LV diastolic dysfunction relies on evaluating the pattern of LV filling. Although this can be assessed by radionuclide, computed tomography (CT), and magnetic resonance imaging (MRI) techniques, cardiac echocardiography, because of its noninvasive and portable nature, is currently the method of choice. Evaluating LV filling, two-dimensional (2-D) anatomic findings, and Doppler flow and tissue Doppler imaging (TDI) variables have emerged as powerful predictors of adverse CV events such as new onset atrial fibrillation (Afib) and HF, as well as mortality, regardless of LVEF.

The symptoms of LV systolic (HFrEF) and diastolic (HFpEF) HF are often identical.
Almost half the patients over 70 years old with HF have HFpEF, and females predominate.
Long-term hypertension (HNT), obesity, sleep apnea, diabetes, and atherosclerosis are risk factors.
The incidence of elderly HFpEF patients is rapidly increasing and expected to equal patients with HFrEF in the near future.
The morbidity and mortality of HFrEF and HFpEF are similar, although currently only therapies for HFrEF have been shown to be effective.
Echo Doppler technique is the only practical and accepted method for diagnosing and staging both types of HF.

The purpose of this chapter will be to describe the various LV filling patterns encountered in clinical practice, and what these patterns and their measurable variables reveal about LV diastolic function in both HFrEF and especially HFpEF. In cases of possible ambiguity ancillary variables such as left atrial (LA) volume, pulmonary venous (PV) flow velocity, and TDI that help in interpreting mitral flow velocity patterns will be discussed.

Left ventricular Filling: A Historical Perspective

In 100 bc Galen proposed that the heart is filled by dilation of the right ventricle. Sixteen hundred years later, in 1628, William Harvey described the heart as a central pump in a circulatory system with both arteries and veins. This was followed by recognition that most cases of HF were due to damage or weakening of the heart muscle and a decrease in the pumping function of the heart. Ventricular filling was considered simply as the interval in which the cardiac chambers filled passively between each pumping cycle and therefore was largely ignored.

Gradually, evidence emerged that abnormalities of ventricular filling could cause symptoms, and that diastolic and systolic LV function were interrelated. About 1915, Wiggers described the phases of the entire cardiac cycle, and the Frank-Starling mechanism was described, whereby LV end-diastolic volume helps regulate LV stroke volume on a beat-to-beat basis. In 1930 Katz recognized the role of LV relaxation in the filling of the ventricle suggesting that the normal heart acts like a “suction” pump, a concept proven 60 years later. A limitation in cardiac filling, not pumping function, with resultant reduced cardiac output was recognized as the cardinal feature of constrictive pericarditis further emphasizing that disorders of filling could also cause cardiac symptoms and disease.

In the 1960s, the study of ventricular biomechanics accelerated. Although most research continued to focus on LV contractile function, cardiac diseases with thickened and noncompliant ventricles such as restrictive and hypertrophic cardiomyopathies were described. Angiographic differences in LV filling patterns between normals and patients with various heart diseases were reported even when the LVEFs were similar, and these were subsequently studied by M mode echocardiography. At the same time, the importance of LV systolic function in determining diastolic restoring forces and rate of LV relaxation was appreciated. Our current view that systole and diastole are an intertwined continuum, with each part affecting the other, gradually began to be accepted.

In the mid-1980s, echocardiographic studies showed that 20% to 40% of elderly patients with HF symptoms had a normal LVEF and therefore presumably isolated diastolic dysfunction causing pulmonary congestion. However, because of the difficulties in quantitating individual LV diastolic properties, the clinical study of LV diastolic dysfunction proceeded slowly. LV filling patterns were analyzed by digitized M mode, angiographic, or radionuclide methods. In 1982 pulsed-wave (PW) Doppler study of mitral flow velocities to study LV filling was reported. Because of its ease of use, noninvasive nature, and ability to determine dynamic changes in LV filling after interventions and over time, this technique revolutionized the study of LV diastolic function. Age-related changes in LV filling were recognized early. Three basic abnormal LV filling patterns were then described using Doppler mitral flow velocity, and correlation was made with LV diastolic variables and filling pressures that were found to be independent of disease state. This suggested that different pathologies altered common diastolic properties. The three abnormal filling patterns were soon found to have clinical significance and prognostic value regardless of cardiac disease type. Pulmonary venous flow velocity helped assess the filling of the left atrium, and variables were found to aid the interpretation of LV filling patterns and pressures. Using the two flow velocities a so-called natural history of LV filling in normals and with disease patterns was described. In addition, manipulation of preload and afterload showed that LV filling patterns changed in response to loading conditions, and that these changes had prognostic significance in patients with cardiac disease. Additional Doppler methods followed, such as the rate of color Doppler mitral inflow propagation velocity (Vp), TDI of mitral annular motion (MAM), and model-based image processing, which continued to improve diagnostic accuracy and advance the new field of diastology.

Although all echo Doppler variables have limitations in interpreting diastolic function, the aggregate sum of the 2-D echo findings and multiple Doppler variables provides a practical way to noninvasively assess LV diastolic function and to objectively follow serial changes after medical intervention or with disease progression. These methods have now been shown to have prognostic value in asymptomatic patients as well as those with HFrEF and HFpEF from various diseases. As a result, the clinical syndrome of HFpEF is now more readily recognized, and studies on improved diagnosis and the best treatment strategies for both symptomatic and asymptomatic patients are being studied.

The strengths of echo Doppler technique in diagnosing diastolic abnormalities, filling pressures, and prognosis are the numerous variables available for analysis.
Attempts to simplify this complex physiology to a few variables has resulted in confusion, most notably that elevated pressures are equivalent to diastolic dysfunction, or the reverse, that normal filling pressures mean normal diastolic function.
The result has been fewer individuals receiving the correct assessment of their diastolic function, a prerequisite for studying possible interventions to reduce future adverse events.

Left Ventricular Filling

Assessment by Doppler Mitral Flow Velocity Patterns and Variables

Because of its noninvasive nature and ease of use, echo Doppler technique has become the accepted clinical standard for assessing LV diastolic function. LV filling is assessed with both continuous wave (CW) and PW Doppler technique. Fig. 9.1 shows the mitral flow velocity obtained with PW Doppler technique and the variables that are measured. These include LV isovolumic relaxation time (IVRT), peak mitral flow velocity in early diastole (E wave) and at atrial contraction (A wave), the mitral deceleration time (mitral DT), the E wave velocity just before atrial contraction (E/A, also sometimes referred to as pre-A velocity), and the duration of mitral A wave velocity (Adur). An E/A wave velocity of more than 20 cm/sec results in a peak A wave velocity that is larger than it would have been at a slower heart rate when mitral flow velocity has time to fall to a lower level before atrial contraction. In these cases, the E/A wave ratio will be reduced compared to values obtained at a slower heart rate, so that more reliance on other echo Doppler variables may be appropriate when interpreting the LV filling pattern.

Besides the simple E/A wave velocity ratio, valuable information is present in the mitral recording, including LV IVRT, mitral DT, and A wave duration.

Fig. 9.1, Mitral flow velocity variables.

Normal and Abnormal LV Filling Patterns at Rest and During Exercise and Their Associated Diastolic Properties

The normal and abnormal LV filling patterns at rest and during exercise, and their associated diastolic properties, are shown in Fig. 9.2 . The numerous factors that affect LV diastolic properties and the filling of the left ventricle are described in 1, 2, 3, 4, 5, 6 . Although the interaction of these is complex, their sum reflects the diastolic transmitral pressure gradient (TMPG), which ultimately determines mitral inflow and the LV filling pattern ( Fig. 9.3 ). A positive LA to LV pressure gradient in diastole results in flow across the mitral valve, while negative gradients decelerate, stop, or reverse flow.

Fig. 9.2, Normal and abnormal LV filling patterns and their associated LV diastolic abnormalities.

Two key diastolic properties, the rate of LV relaxation (diastolic pressure fall) and LV compliance throughout diastole, are especially important in understanding pressures and LV filling. Normal LV contraction and relaxation are vigorous and rapid, with diastolic elastic recoil augmenting early diastolic filling through a suction effect, meaning initially LV volume increases while pressure is still decreasing. This promotes an early mitral valve opening and helps maximize the diastolic filling period and the time available for myocardial perfusion. At normal resting heart rates (<75 bpm) rapid ejection and a predominance of early diastolic filling leaves a period of diastasis before atrial contraction as a reserve that can help maintain adequate LV filling when exercise shortens cardiac cycle length.

The first hemodynamic abnormality seen in nearly all cardiac diseases is a slower rate of LV relaxation. This is most commonly associated with hypertension or LV hypertrophy. Both systole and diastole are affected even when the LVEF remains normal. In systole the LV isovolumic contraction and ejection times become prolonged. In diastole the impaired LV relaxation causes a slower fall in LV pressure after aortic valve closure. This causes the mitral valve to open later and the early diastolic TMPG and proportion of filling to decline. The diastasis period often disappears, and a greater proportion of filling at atrial contraction is needed to reach an optimal end-diastolic volume. These changes shorten the time available for diastolic filling and alter the LV filling pattern ( Fig. 9.4 ). Patients who have this impaired relaxation (IR) filling pattern most often have normal filling pressures and are asymptomatic, although a few may show a blunted cardiac output and functional limitation with exercise.

Numerous factors affect LV diastolic properties, but their sum defines the transmitral pressure gradient, which determines mitral inflow and the LV filling pattern.
The two most important diastolic properties are the rate of relaxation and LV compliance, the latter affecting LA and LV filling pressures.
The most common cause of early LV diastolic dysfunction is LV hypertrophy due to HTN heart disease, which slows relaxation and reduces early diastolic filling.
However, in IR patients, pressures remain normal and the patients asymptomatic, sometimes for decades in this largest group of patients with early diastolic dysfunction.

Fig. 9.3, The major determinants of LV filling are shown. In sum they affect the transmitral pressure gradient (TMPG), which determines the LV filling pattern. When LV pressure falls below LA pressure a positive pressure gradient occurs and early diastolic filling begins (hatching). Pressure in the ventricle rises and then briefly exceeds LA pressure, which decelerates mitral flow velocity. A positive pressure gradient occurs again at atrial contraction and results in flow in late diastole just before systole begins.

With more advanced disease LV relaxation remains abnormal, but a decrease in LV compliance occurs first in late diastole after atrial contraction and then throughout diastole, which increases mean LA pressure and size and begins to result in symptomatic HF. The increased LA pressure will oppose the effect of a slower rate of LV relaxation, causing an earlier mitral valve opening and higher TMPG so the LV filling pattern appears like normal. However, in this case the increase in early diastolic LV filling is due to increased driving (LA) pressure rather than suction created by normal ventricular elastic recoil. Patients with this pseudonormal LV filling begin to have HF symptoms and show moderate functional limitation.

With a severe decrease in LV compliance the marked elevation in LA pressure causes atrial dilation and failure, and early diastolic filling predominates with only a small and abbreviated amount of late diastolic filling. This third and most abnormal LV filling pattern is termed restrictive (RST). Patients with RST filling patterns still have impaired LV relaxation, but the severe decrease in LV compliance and marked elevation of LA result in an increased proportion of early diastolic filling that has an abrupt, premature termination (short mitral DT) with little filling at atrial contraction. Patients with this pattern are markedly symptomatic, demonstrate severe functional impairment, and have a poor prognosis.

LV chamber compliance includes myocardial stiffness as well as elements such as volume, which stretch the myocardium or the pericardium and thus constrain cardiac dilation.
Intrinsic myocardial stiffness is affected by cardiac interstitial elements such as collagen and by myocardial elements such as titin.
Although LA and LV filling pressures may increase with volume overload, diastolic dysfunction is only present when myocardial stiffness is increased, first only near maximum end-diastolic volume, which elevates LV end-diastolic pressure (EDP).
With progressive increase in stiffness LV filling pressures are elevated throughout diastole and raise mean LA pressure, an advanced stage of disease.

An increase in heart rate as with exercise is the heart’s diastolic stress test. As heart rate increases, the diastolic filling time shortens. In normal individuals a coordination of the electrical and mechanical systems provides for increased filling and cardiac output without an elevation of diastolic pressures. These include shortening of the PR interval, as well as faster heart rates triggering the treppe (or staircase) effect, which increases LV contractility and rate of relaxation. LVEF increases and end-systolic volume decreases. The overall effect is an earlier mitral valve opening, increased elastic recoil, and a larger early diastolic TMPG. LV contractility is also increased by sympathetic tone, while systemic vascular resistance falls.

Impaired relaxation may reduce the cardiac output achieved by reducing the diastolic filling time below that needed for optimal LV filling and myocardial perfusion. A premature fusion of early and late diastolic filling often occurs (see Fig. 9.4 ), and atrial contraction may occur into an incompletely relaxed left ventricle. The inability to increase LV end-diastolic volume with exercise leads to a blunted increase in cardiac output and reduced exercise capacity. Patients with pseudonormal and RST filling patterns also have a significant decrease in exercise capacity, but in these individuals it is more likely an increase in mean LA pressure due to reduced LV compliance that limits exercise than an inability to increase LV end-diastolic volume.

Changes in Mitral Flow Velocity Patterns With Aging Together With Disease States

The Natural History of LV Filling

Elastic recoil and rapid LV relaxation in adolescents and young adults result in a predominance of early diastolic filling (E wave) with much less filling (10–15%) due to atrial contraction. With normal aging LVEF changes little, but LV relaxation slows in most individuals. The slower relaxation appears to be largely due to a gradual increase in systolic blood pressure (BP) and LV mass. The result is reduced LV filling in early diastole and increased filling at atrial contraction. In most individuals, the peak E and A wave velocities become approximately equal during the sixth and seventh decades of life, with atrial filling contributing up to 35% to 40% of LV diastolic stroke volume. In individuals who maintain lower BPs and have no increase in LV mass, the age-related changes of decreasing E/A wave ratio in asymptomatic normal patients used in most reference studies are less pronounced, and normal E wave predominance can occasionally be seen into the seventh decade of life. In these individuals, normal 2-D findings, LA size, and annular TDI variables confirm that diastolic function is normal. Normal age-related values for mitral flow variables are listed in Table 9.1 .

With aging LV relaxation slows in most individuals causing a reduced E/A wave ratio, which appears to be largely due to a gradual increase in systolic BP and LV mass.
Published normal values for diastolic variables in the over 70 years age group are difficult to define because few studies have convincing data that the asymptomatic patients used were truly normal.

Table 9.1

Mitral flow velocity in normals: age-related changes

AGE (yr)	n	IVRT (msec)	E (mmHg)	A (mmHg)	MDT (msec)	ADUR (msec)
2–20	46	50 ± 9	88 ± 14	49 ± 12	142 ± 19	113 ± 17
21–40	51	67 ± 8	75 ± 13	51 ± 11	166 ± 14	127 ± 13
41–60	33	74 ± 7	71 ± 13	57 ± 13	181 ± 19	133 ± 13
>60	10	87 ± 7	71 ± 11	75 ± 12	200 ± 29	138 ± 19

Normal age-related values for mitral E and A wave velocities, and mitral E/A wave ratios are shown ± SD. All individuals were free of cardiac disease, and had a normal blood pressure, physical exam, ECG and treadmill ECG with >100% functional aerobic capacity for age, normal BP response and no ECG abnormalities. LV hypertrophy was excluded, and all E at A velocities were less than 20 cm/sec so that the peak A wave velocity was not increased above that expected for the aging process.

Adur, Duration of mitral A wave; IVRT, isovolumic relaxation time; Mdt, mitral deceleration time.

All measured by LK Hatle; unpublished data; used with permission.

The three basic abnormalities of LV filling patterns were discussed previously and shown in Fig. 9.2 . The arrows in the figure indicate that abnormal mitral filling patterns are a dynamic continuum and may worsen or become more normal with changes in loading conditions. Common usage describes the three abnormal filling patterns as IR, pseudonormal, and RST. Impaired LV relaxation is present in all patterns; the difference being that with pseudonormal and RST filling, mean LA pressure is abnormal and progressively higher as LV compliance becomes more reduced and abnormal.

The changes in LV filling with normal aging and the changes with cardiac disease states can be combined into a natural history of LV filling, which is shown together with their corresponding pulmonary venous flow velocities ( Fig. 9.5 ). Although theoretical when proposed in 1992, the progression of abnormalities in LV filling patterns with disease states (from IR to pseudonormal to RST), together with changes in LV relaxation and compliance, has been documented in experimental models of congestive HF and clinically observed in patients with restrictive cardiomyopathies. Gradations in LV filling patterns between the three basic abnormal patterns are common due to the multiple variations of the degree of LV relaxation and compliance abnormalities. However, the abnormal LV filling patterns remain specific to the alterations in diastolic properties rather than the type of cardiac disease, with all three patterns, depending on disease stage, being seen in disorders as diverse as restrictive and dilated cardiomyopathies.

$Fig. 9.4, The effect of impaired LV relaxation on LV diastolic filling time (DFT) and LV filling patterns. (A) ECG, PW Doppler of mitral flow velocity, and high-fidelity LV pressure recordings are shown in two individuals at rest. Both individuals have heart rates of 75 bpm and a normal LV ejection fraction. In the normal subject LV pressure increases and decreases rapidly so that the DFT is longer than systole (SYS) with a period of diastasis in mid-diastole. In contrast (top right), with impaired LV relaxation longer isovolumic contraction and relaxation times result in the DFT being longer than systole. As a result the LV filling pattern is markedly altered to achieve the same end-diastolic volume, with less filling in early diastole, a disappearance of diastasis, and a larger contribution of filling at atrial contraction. (B) The effect of increased heart rates on diastolic filling time LV pressure (LVP) is shown in the same two individuals at rest and with exercise. At 125 bpm the DFT with impaired LV relaxation is markedly abbreviated compared to normal and only 25% as long as systole making it difficult to maintain adequate LV filling. The result is a reduced end-diastolic volume, blunted cardiac output, and reduced functional aerobic capacity.$

This natural history of LV filling explains how both young normal individuals and patients with severe disease and a restrictive filling pattern can have a high proportion of filling in early diastole and an audible S ₃ gallop. It also shows that pulmonary flow velocity has its own changes that occur with normal aging and in cardiac disease states (discussed later in the chapter), and that these associated PV filling patterns are more distinctive than some similar appearing normal and abnormal mitral flow velocity patterns.

Three basic abnormal LV filling patterns exist, which are descriptively called impaired relaxation, pseudonormal, and restrictive.
All have slowed LV relaxation, the difference being pseudonormal and restrictive have an elevated LA pressure, which increases early diastolic filling and thus masks the slowed relaxation.
Restrictive LV filling occurs with markedly abnormal myocardial stiffness, which terminates filling abruptly and has a poor prognosis.
Changes in PV patterns follow changes in the abnormal mitral filling patterns and provide valuable information on identifying increased mean LA pressure as well as helping stratify patients with pseudonormal filling patterns.

LV Filling and Changing Cardiac Loading Conditions

Simple maneuvers in the echo laboratory to reduce (Valsalva) or increase (leg raising) venous return demonstrate that mitral flow velocity patterns are a dynamic continuum. During the strain phase of a Valsalva maneuver, preload (mean LA pressure) is reduced and alters the LV filling pattern that is present ( Fig. 9.6 ). In normals, peak mitral E wave velocity decreases by at least 20% during maximum strain with a smaller decrease in peak A wave velocity. Similarly, in patients with IR filling pattern, mean LA pressure is normal so that with preload reduction the TMPG decreases and both E and A wave velocities decrease. In patients with reduced systolic function and IR pattern, increasing preload by leg raising may result in no change in the filling pattern. However, if a pseudonormal mitral flow velocity pattern results, it indicates a higher cardiovascular morbidity than if the E/A ratio remains less than 1.

Fig. 9.5, The natural history of LV filling patterns with normal aging and with progressive diastolic dysfunction as assessed by PW Doppler mitral and pulmonary venous flow velocity recordings. Several abnormal LV filling patterns have E/A wave velocity ratios, which are similar to those seen in normal individuals. This can occur because different combinations of LV relaxation and LA pressure may result in the same early diastolic TMPG and hence a similar mitral flow velocity pattern. For this reason, additional data, such as pulmonary venous flow velocity, is often helpful in distinguishing normal and abnormal mitral filling patterns, especially of the pseudonormal type. A, Peak mitral flow velocity at atrial contraction; E, peak mitral flow velocity in early diastole; IVRT, LV isovolumic relaxation time; PVa, reverse pulmonary venous flow at atrial contraction; PVd, pulmonary venous flow velocity in diastole; PVS, pulmonary venous flow velocity in systole.

With pseudonormal mitral flow patterns, the Valsalva strain lowers the elevated LA pressure and unmasks the underlying impaired LV relaxation. A notable feature of this change is the increase in mitral A wave velocity and duration as the left atrium ejects into a ventricle that has less volume and a lower pressure. In patients with RST filling patterns, preload-sensitive individuals will revert to a pseudonormal filling pattern. If a RST pattern does not improve with an adequate Valsalva manuever, LV stiffness is markedly increased even when LA pressure is lowered or normalized, and these patients have a very poor prognosis.

LV filling patterns are dynamic and change with loading conditions that affect the transmitral pressure gradient.
By reducing venous return and LA pressure the Valsalva maneuver is especially helpful in unmasking a pseudonormal filling pattern to its underlying IR pattern.
As loading conditions affect LV filling the most accurate assessment of cardiac diastolic properties in all individuals occurs when both the central venous pressure (CVP) and BP are normal.

Grading the Degree of LV Diastolic Dysfunction by Mitral Flow Velocity Pattern Alone

A simplified grading system for diastolic function based on the three abnormal mitral flow velocity patterns has been proposed and is shown in Fig. 9.7 . Grades Ia and Ib are both IR patterns with normal mean LA pressure and LA size. The difference is whether LV filling pressures are normal (Ia) or LV EDP is elevated (Ib). This is important because an elevated LV EDP is the first hemodynamic abnormality of diastolic dysfunction, and these patients, although usually asymptomatic, have a significant increase in future cardiovascular events. Grade II indicates mean LA pressure is increased with pseudonormal filling, and Grade III is restrictive LV filling. Grade IV is RST filling that does not become pseudonormal with preload reduction indicating the most advanced LV diastolic dysfunction and the worst prognosis.

Fig. 9.6, Changes in mitral flow velocity patterns to preload reduction using the Valsalva maneuver. The left panel shows PW mitral flow velocity recordings from a normal individual and a patient with pseudonormal LV filling. After Valsalva the normal has both E and A wave velocity decrease with little change in E/A ratio, while the lowering of LA pressure in the pseudonormal patient unmasks an IR LV relaxation pattern. The right panel shows in tabular form the different responses seen in mitral LV filling patterns with a Valsalva maneuver after ∼10 sec of strain. In all but fixed restrictive the E wave velocity should decrease at least 20%. When mean LA pressure is normal the mitral A wave velocity also decreases. No A wave change with an IR filling pattern suggests an elevated LV end-diastolic pressure. With mean LAP increased pesudonormal filling reverts to IR filling, and most RST patterns to pseudonormal. The exception is irreversibly RST where advanced disease results in no change in filling even with a moderate decrease in mean LA pressure.

Although grading LV diastolic dysfunction by mitral flow velocity pattern alone can be helpful, many patients (especially the elderly) may be misclassified. The degree of abnormality in LV relaxation and the LV compliance and filling pressures are a continuum, and similar LV filling patterns are possible with different combinations of these two diastolic properties. Later sections will emphasize a major area of misinterpretation is patients with markedly impaired LV relaxation, where LA pressure is elevated with an increase in E wave velocity, yet the filling pattern appears to be impaired (E/A ratio <1) because of partial fusion of early and late diastolic filling.

Fig. 9.8 shows an extreme example of how different combinations of the speed of LV relaxation and LA pressure may result in similar looking normal LV filling patterns. In this case three individuals with hypertrophic cardiomyopathy have E/A wave ratios of approximately 2, yet their mean LA pressure varies threefold because of the markedly different rates of LV relaxation. In these cases ancillary data such as 2-D anatomic abnormalities, reduced LVEF, LVH, LA enlargement, altered PV flow, or annular TDI velocities are indicators that abnormal diastolic function and pressures are present. Also some mitral filling patterns are atypical, meaning that a biphasic mitral deceleration time, mid-diastolic filling hump, or some other unusual feature is present. These less common LV filling patterns do not fit well into the simplified grading schemes for diastolic HF (DHF) that use only the mitral flow velocity pattern, and are best understood by evaluating the abnormal diastolic properties and physiology that the altered LV filling reflect.

Since the LV filling pattern reflects the transmitral pressure gradient, the more impaired the LV relaxation the higher the LA filling pressure will need to be to exhibit a pseudonormal pattern.
In these cases, which usually have a nonlinear mitral deceleration decay, ancillary variables such as LV IVRT, mitral A wave duration, and PV flow velocity pattern are used to reach a conclusion regarding diastolic properties and filling pressures.

Fig. 9.7, A simplified grading system for diastolic dysfunction is shown, which assigns each abnormal mitral flow velocity pattern to a progressively more advanced grade of diastolic HF. Impaired relaxation (IR) Ia has normal filling pressures, while IR+ Ib has an increase in LV EDP, the first hemodynamic abnormality that occurs in diastolic dysfunction. Grade III is restrictive (RST), which will revert to a pseudonormal (PN) pattern with Valsalva maneuver and LA pressure (preload) reduction, while Grade IV DHF will not, an ominous prognostic sign.

Grading the Degree of LV Diastolic Dysfunction in Epidemiology Studies

Recent landmark studies show that many asymptomatic individuals with a normal LVEF have abnormal diastolic function, which is a risk factor for future development of adverse CV events such as new onset HF, first episode of Afib, stroke, and increased death. In an effort to improve predictive value above that by analyzing mitral flow velocity alone, classifying the degree of LV diastolic abnormality in these studies included mitral inflow velocity variables (especially the E/A wave ratio), their response to Valsalva maneuver, PV flow velocity, and TDI of the mitral annulus. Fig. 9.9 shows the multiple echo Doppler criteria for grading diastolic dysfunction in these epidemiologic studies and provides a preview of the ancillary variables that aid in this interpretation that will be discussed in the next section.

Fig. 9.8, An illustration of how different combinations of impaired LV relaxation and LA pressure can result in mitral flow velocity patterns with similar E/A ratios but markedly different filling pressures. The PW mitral recordings shown are from three patients with hypertrophic cardiomyopathy. The patient on the left is the most normal, with the least impaired LV relaxation and a normal mean LAP. The patient on the right has a similar LV filling pattern but marked diastolic dysfunction, with severely impaired LV relaxation and a mean LA pressure of 30 mmHg. In these cases, the simplified grading system of diastolic dysfunction in Fig. 8 would be misleading, and other ancillary variables would indicate the degree of diastolic HF.

Interpretation of Individual Mitral Flow Velocity Variables

Left Ventricular IVRT Interval

This is the interval from aortic valve closure to mitral valve opening and the start of mitral inflow (see Fig. 9.1 ). This interval can be a powerful tool in patients with heart disease in helping to evaluate diastolic dysfunction and especially LA filling pressure. We suggest it be measured on all echo Doppler studies.

In normals, IVRT varies with age, being shorter in the young who have rapid LV relaxation that results in an earlier mitral valve opening and then lengthening as relaxation slows with age (see Fig. 9.3 and Table 9.1 ). Fig. 9.10 shows the effect of changes in the rate of LV relaxation and LA pressure on the IVRT interval, timing of mitral valve opening, and LV filling pattern in a middle-age subjects.

Fig. 9.9, A more complicated grading system for LV diastolic dysfunction that incorporates multiple mitral flow velocity variables, their response to Valsalva maneuver, PV flow velocity variables, and TDI of the septal mitral annulus. These criteria have been used in epidemiologic studies to assess the asymptomatic prevalence of diastolic dysfunction in the community and to understand how LV diastolic dysfunction increases the risk for future adverse cardiac events.

The IVRT interval is most easily interpreted when at its extremes, meaning furthest from expected norms, being either short (<60 msec) or long (>110 msec). When between these values, interpretation requires correlation along with other echo Doppler variables. A normal IVRT for a middle-aged adult is approximately 80 msec. A short IVRT (<60 msec) indicates an early mitral valve opening, a long IVRT (>100 msec) delayed LV relaxation, usually with a normal LA pressure, and a late valve opening. In patients with IR filling and normal pressures, a prolonged IVRT is an early indicator of LV diastolic dysfunction. If mean LA pressures remain normal, extremely slow LV relaxation can result in IVRT values that may approach 200 msec. The higher LA pressure in pseudonormal filling patterns causes the mitral valve to open earlier, so the IVRT shortens back to more normal values of 60 to 100 msec, and the IVRT value is less useful than other assessed variables. A short IVRT of 40 to 60 msec is seen in young, healthy, normal individuals or in patients with very high mean LA pressure and RST filling. This clinical distinction is easily made by the normal versus abnormal 2-D anatomic findings, especially LA size and contractile function.

A common instance that IVRT duration can be very helpful is when heavy mitral annular calcification is present and there is a question of mild calcific mitral stenosis versus LV diastolic dysfunction. The mitral annular narrowing may increase E wave velocity, the E/A wave ratio, and LA size, making the assessment of LV diastolic dysfunction difficult. If the pressure half-time is normal or borderline but the IVRT is short (20 msec less than that expected for age) LA pressure is likely elevated. Conversely, if E wave velocity is increased but the IVRT is normal, the annular narrowing is likely the cause for the increased velocity. A significant transmitral gradient and markedly prolonged pressure half-time indicate calcific mitral stenosis, in which case a short IVRT would also indicate increased mean LA pressure similar to the auscultatory findings of a short opening snap interval.

The LV IVRT directly reflects LA pressure, but age and an expected rate of LV relaxation for the findings present have to be assessed.
When the IVRT is markedly prolonged, LA pressure is very likely normal.
With advanced cardiac pathology a short LV IVRT indicates LA pressure is elevated.

IVRT Flow

IVRT flow refers to flow, usually apically directed, from one part of the ventricle to another that occurs during the IVRT period when both aortic and mitral valves are closed. The importance of recognizing IVRT flow is twofold: It indicates abnormal dyssynchronous LV relaxation is present between apex and base, and it should not be confused with the mitral E wave velocity that immediately follows it. In the normal situation no significant LV flow is detected during the IVRT period. When present, IVRT flow is most easily detected from an apical transducer position with CW or color M mode (CMM) Doppler because both techniques scan the long axis of the ventricle. PW Doppler can then be used for better velocity definition. IVRT flow is usually 20 to 60 cm/sec but can occasionally be as high as 1 to 2 m/sec ( Fig. 9.11 ).

Fig. 9.10, The isovolumic relaxation time (IVRT).

When IVRT flow is present, the most common cause is late systolic LV narrowing and increased flow velocities at the papillary muscle level, either due to LV hypertrophy or hyperdynamic systolic function. The increased mid-systolic or late systolic load placed on the LV apical segments due to the mid-systolic LV narrowing causes the apex to relax prematurely before the basal myocardial segments, with blood flow moving toward the lower pressure in the apex before the mitral valve opens. Bidirectional IVRT flow is occasionally seen when apical flow is followed by flow reversing and flowing back toward the LV base as basilar relaxation reduces pressure below that in the apex. IVRT flow can also be observed in the left ventricle with dyssynchronous LV relaxation due to coronary artery disease (CAD) or left bundle branch block (LBBB) and in the right ventricular (RV) apex when it is hyperdynamic and exhibits cavity obliteration.

IVRT flow reflects dyssynchrous LV relaxation as is best seen by CMM or CW Doppler from an apical four-chamber view.
The most common cause is a small LV cavity with a late peaking dagger-shaped increase in velocity in the midventricle in late systole, with IVRT flow seen just below that level.

Mitral Time Velocity Integral

Though rarely considered when discussing the assessment of LV diastolic function, the absolute value of the mitral time velocity integral (TVI) is often helpful in interpreting mitral flow velocity patterns. In the absence of significant mitral (MR) or aortic (AR) regurgitation, mitral TVI multiplied by mitral valve cross-sectional orifice area represents the LV stroke volume. Cardiac output is this stroke volume times the heart rate. Since the mitral orifice is larger than the aortic annulus the mitral TVI should be smaller than the LV outflow tract (LVOT) TVI by about 30%.

If cardiac output is either elevated or decreased the mitral to LVOT TVI ratio should remain normal. With significant MR or mitral stenosis (MS), the mitral TVI will increase and be nearly as large or larger than the LVOT TVI. With isolated AR the reverse will be true in relation to its severity. As early and late diastolic mitral TVIs represent the sum of LV filling, an inverse relation exists. A large early diastolic mitral TVI will be associated with a smaller TVI at atrial contraction. Conversely, when the E wave TVI is decreased, the ventricle can only reach a normal end-diastolic volume if there is a corresponding increase in A wave TVI. If mitral E and A waves are partially fused at rest due to impaired LV relaxation, a LBBB, or first-degree AV block (prolonged PR interval), a low proportion of E wave versus A wave TVI may be present. These patients often have a reduced functional aerobic capacity because of an inability to increase LV diastolic volume (their mitral TVI) adequately with exercise.

In the absence of significant MR the mitral TVI reflects LV filling and stroke volume.
Fused LV inflow patterns often have reduced mitral TVIs, which may limit cardiac filling and output, especially with exercise.
When LV filling occurs only with LA contraction, the ability to increase ventricular filling and output with exercise is markedly reduced even if LA pressure is normal at rest.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here