Eur J Echocardiography (2002) 3, 75-79
`doi:10.1053/euje.2001.0136, available online at http://www.idealibrary.com on
`
`TEACHING CORNER: REVIEW
`
`Non-invasive Estimation of Left Ventricular Filling
`Pressures by Doppler Echocardiography
`
`M. Pozzoli', E. Traversi 2 and J. R. T. C. Roelandt3
`
`'Department of Cardiology, A. Manzoni Hospital, Lecco, Italy; 2Department of Cardiology, S. Maugeri
`Foundation, IRCCS, Centro Medico, Montescano, Italy; 3Department of Cardiology, Thoraxcenter,
`Erasmus University Medical Center, Rotterdam, The Netherlands
`
`Besides being complicated reality,
`in my experience, is odd ....
`Of course anyone can be simple
`if he has no facts to bother about
`C. S. Lewis
`
`Heart failure is haemodynamieally characterized by
`elevated left ventricular filling pressure. Its determi-
`nation is important in order to optimize unloading
`therapy, interpret equivocal symptoms, predict prog-
`nosis and the follow-up of treatmentsl' 1. Invasive tech-
`niques are impractical for repeated measurements.
`Therefore there is a need for more comfortable and less
`expensive methods of measurement.
`Over the past 10 years, pulsed-wave Doppler echo-
`cardiography has emerged as a practical tool for the
`non-invasive estimation of left ventricular filling pres-
`sures and several indices derived from transmitral and
`pulmonary venous flow velocity recordings have been
`validated for estimating left ventricular filling pressures
`in various subsets of patients with both systolic and
`diastolic left ventricular dysfunction, excluding those in
`whom left ventricular filling is affected by extrinsic
`factors such as mitral stenosis or pericardial constraint.
`The basic principle of all these methods is that blood
`flow is driven from the left atrium into the left ventricle
`by the instantaneous pressure gradient across the mitral
`valve and that mitral flow velocity therefore reflects the
`level of left atrial pressure 12,31. However, since the trans-
`mitral pressure gradient (and flow velocity) is deter-
`mined not only by left atrial pressure, but depends also
`on ventricular factors such as relaxation rate and com-
`pliance, the correlations between Doppler variables and
`
`Address correspondence to: Massimo Pozzoli, Department of
`Cardiology, A. Manzoni Hospital, Via della Filanda, Lecco, Italy.
`Tel: +39-0343-489111; E-mail: maxpozz@libero.it
`Received 2 July 2001, revised manuscript received 15 November
`2001; accepted 20 November 2001.
`
`left atrial pressure are too weak for an accurate estima-
`tion and may vary between different subsets of patients.
`In fact, the rate of left ventricular relaxation affects left
`ventricular pressure fall in early diastole and conse-
`quently plays an important role in determining the E
`wave velocity. Thus, when the rate of left ventricular
`relaxation is high (such as in normal young subjects
`and in hyperthyroid patients) the early diastolic wave
`velocity (E) and its deceleration may be increased even if
`the left atrial pressure is low. Conversely, when relaxa-
`tion is markedly impaired (such as in patients with
`severe left ventricular hypertrophy and diastolic heart
`failure) E wave velocity and its deceleration rate may be
`relatively low even in the presence of elevated left atrial
`pressure. The opposite effects of left atrial pressure and
`impaired left ventricular relaxation may make it difficult
`to estimate left ventricular filling pressure in a given
`patients on the basis of transmitral flow velocity wave
`alone.
`To overcome the confounding effects of the multiple
`interacting factors that affect transmitral flow velocities,
`several strategies are followed. First of all Doppler
`indices should be considered in the context of the clinical
`picture (age, heart rate, etiology of the disease, etc.) and
`the M-mode and two-dimensional echocardiographic
`findings (left atrium and left ventricular dimensions and
`systolic function). For example, in a patient with a
`dilated left ventricle and poor systolic function we
`know that left ventricular relaxation is impaired.
`Consequently, a high amplitude E wave with rapid
`deceleration must be due to high left atrial pressure and
`a non-compliant left ventricle. On the other hand, in a
`patient with poor systolic function and a delayed or
`reduced E wave followed by a slow deceleration and
`an increased late diastolic A wave velocity left ventricu-
`lar filling pressures are normal or mildly elevated.
`Consequently, several studies have shown that in
`patients with severe systolic dysfunction and normal
`sinus rhythm the correlation between simple variables,
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`1525-2167/02/010075+05 $35.00/0 (cid:9)
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`U 2002 Published by Elsevier Science Ltd on behalf of The European Society of Cardiology
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`76 M. Pozzoli et al.
`
`such as EIA and deceleration time, and left ventricular
`filling pressure are excellent 14-71.
`The estimation of left ventricular filling pressures in
`conditions where left ventricular dysfunction is less
`apparent can be improved by the analysis of the pul-
`monary vein flow velocity pattern. The pulmonary vein
`flow velocity pattern mirrors the changes of the
`left atrial pressure. When the left atrium pressure is
`elevated and, particularly, when there is a high V-wave
`because of a non-compliant left atrium, the systolic
`forward flow velocity (S wave) decreases while the
`diastolic velocity (D wave) increases. Although systolic
`pulmonary venous flow velocity is determined by
`multiple factors (including left ventricular systolic func-
`tion, left atrium relaxation, right ventricular vis a tergo
`and mitral regurgitation), the systolic forward flow
`velocity in patients with left ventricular systolic dysfunc-
`tion is strongly and inversely related to the left ventricu-
`lar filling pressures. In particular, a systolic fraction
`<40% is a reliable index of a pulmonary artery wedge
`pressure >18 mmHg 1B"101. However, in young normal
`subjects, in patients with eccentric mitral regurgitation
`and in those with a cardiac allograft a blunted S wave
`may be present even when left ventricular filling pres-
`sures are low. Conversely, in patients with good left
`ventricular systolic function and vigorous displacement
`of the mitral annulus, the S wave can be relatively high
`in spite of high filling pressures.
`Another useful index for estimating left ventricular
`filling pressure is the difference between the duration of
`the reverse pulmonary vein flow wave (Ar) and of the
`mitral forward A wave (Fig. I). In normal subjects the
`duration of these two waves is almost equal. When
`the left atrium contracts against a stiff ventricle, the
`forward flow across the mitral valve stops early while the
`reversed flow into the pulmonary veins increases. Thus,
`an Ar wave duration longer than that of the transmitral
`A wave is an accurate sign of a left ventricular end-
`diastolic pressure > 15 mmHgl' 1. This index has the
`additional advantage of being independent of age, mitral
`regurgitation and left ventricular systolic function. It
`should be noted that although this index is strongly
`correlated with left ventricular end-diastolic pressure, its
`correlation with pulmonary wedge pressure is rather
`poor. The fact that patients with a high left ventricular
`end-diastolic pressure may occasionally have mildly
`elevated or even normal early diastolic left atrium pres-
`sures accounts for this discrepancy. Other limitations of
`this index are: the difficulty of recording Ar wave
`duration in patients with dilated left atrium and pul-
`monary veins; its dependence on atrial systolic function
`and its merge with the diastolic forward flow when
`the heart rate is high and/or the PR interval is long.
`Technical details on how to obtain and correctly
`measure this and other transmitral and pulmonary
`venous flow vardiables can be found in a comprehensive
`review published by Appleton 1t ~1 .
`Despite these limitations, the analysis of pulmonary
`vein flow in combination of transmitral flow in order to
`differentiate normal from pseudonormal velocity pat-
`
`Eur J Echocardiography, Vol. 3, issue 1, March 2002
`
`terns improves the estimation of left ventricular filling
`pressures in patients with moderately impaired function
`and dilated left ventricles.
`There remains, however, a sizeable number of patients
`in whom even this method is not reliable enough:
`patients with a single transmitral flow wave due to
`tachycardia and /or a prolonged PR interval; patients in
`atrial fibrillation, those who have isolated diastolic dys-
`function; those with a cardiac allograft and those with
`inadequate Doppler recordings of pulmonary vein flow.
`Two methods have been recently proposed to estimate
`left ventricular filling pressures. The first method com-
`bines transmitral E wave velocity with its propagation
`velocity (Pv) into the left ventricular recorded by colour
`M-mode Doppler. The second method combines trans-
`mitral E wave velocity with the early diastolic velocity of
`the mitral annulus motion recorded by pulse-wave tissue
`Doppler. Both of these methods are based on the
`concept that normalizing transmitral E wave velocity by
`an index that reflects the rate of left ventricular relaxa-
`tion which is independent from pre-load reduces the
`confounding effect of the relaxation rate and improves
`the correlation with left atrial pressure. It has been
`shown by several studies that the wavefront of the early
`diastolic inflow velocity reaches the left ventricular apex
`almost instantaneously when the relaxation rate is high,
`while it takes longer when relaxation is impairedl 13,141
`The Pv of this wavefront can be assessed by color
`M-mode in the apical four-chamber view with the beam
`aligned with the centre of the left ventricular inflow. The
`slope of the first colour aliasing (set at 45 cm/s) from the
`mitral annulus to 4 cm into the left ventricular is then
`identified, either visually or by isovelocity maps [J41. This
`measurement is strongly related to the time constant
`(tau) of the left ventricular pressure decay and the E /Pv
`ratio with pulmonary wedge pressure. Recent observa-
`tions, however, suggest that this method is more reliable
`in patients with dilated ventricles while its accuracy is
`limited in patients with normal systolic function and
`13,141
`small left ventricles ~
`Like Pv, the velocity of early diastolic mitral annulus
`motion (E') has also been found to be related to tau and
`to be relatively independent of left atrial pressure [15,161.
`Again the E/E' ratio has been successfully applied to
`estimate left ventricular filling pressures in subsets of
`patients, including those with atrial fibrillation, sinus
`tachycardia, cardiac allograft and normal systolic
`funetiont17 201 . An early study indicated that a E/E' ratio
`>10 is a reliable index to estimate a pulmonary wedge
`pressure > l2 mmHg [151. A more recent study showed
`that an E/E' ratio <8 accurately identifies patients with a
`normal pressure and a ratio > 15 those with an elevated
`pulmonary wedge pressurel 2'1. In patients with inter-
`mediate values (>8 and <15) pulmonary wedge pres-
`sures may vary widely and the other Doppler flow
`methods can be used. It remains unresolved whether
`better results can be obtained using the lateral or the
`septal E'. In patients with isehaemic heart disease it is
`probably best to average the values obtained from the
`lateral, septal, anterior and inferior mitral annulus. The
`
`076
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`
`Non-invasive Estimation of Left Ventricular Filling Pressures 77
`
`ECG
`
`u\~
`
`PVF
`
`TDI
`
`COLOF
`M-mode
`
`Figure 1. Parameters used for the estimation of left ventricular filling
`pressures.
`Pulsed Doppler of transmitral flow (MVF): isovolumic relaxation period
`(IRP); early diastolic (E) and late diastolic (A) wave amplitude; deceleration
`time (DT); late diastolic wave duration (Adur). Derived measurements:
`ratio between early diastolic and late diastolic wave amplitude (E/A);
`deceleration rate (E/DT). Pulsed Doppler of pulmonary vein flow (PVF):
`systolic forward flow wave amplitude (S) ; diastolic forward flow wave
`amplitude (D); diastolic reverse flow duration (Ardur). Derived measure-
`ments: systolic fraction (S/S+D); difference between diastolic reverse flow
`duration of pulmonary venous flow and late diastolic wave duration of
`mitral flow (Ar-A duration). Tissue Doppler of mitral annulus (TDT):
`amplitude of early diastolic wave (E'); amplitude of late diastolic wave (A');
`Derived measurements: ratio between early diastolic wave amplitude of
`transmitral flow and early diastolic wave amplitude of mitral annulus
`(E/E'). Colour M-mode Doppler of transmitral inflow: propagation velocity
`of early diastolic flow (Pv) calculated as the slope of the first aliasing
`(45 cm /s) from the mitral valve plain to 4 cm into the left ventricle. Derived
`measurements: ratio between early diastolic wave amplitude of transmitral
`flow and its propagation velocity into the left ventricule (E/Pv).
`
`Eur J Echocardiography, Vol. 3, issue 1, March 2002
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`78 M. Pozzoli et al.
`
`Table 1. Parameters for identification of patients with an
`elevated left ventricular filling pressure.
`
`• Enlarged left atrium size
`• E/A ratio >2
`• DT <150 msec
`• SF of pulmonary vein flow <40%
`• E/E' ratio >15
`• E/Pv >2
`
`DT: deceleration time of early diastolic wave of transmitral flow;
`E/A: ratio between early diastolic and late diastolic wave amplitude
`of transmitral flow; E/E': ratio ratio between early diastolic wave
`amplitude of transmitral flow and early diastolic wave amplitude of
`mitral annulus; EIPv: ratio between early diastolic wave amplitude
`of transmitral flow and its propagation velocity into the left
`ventricular. LA: left atrium. SF: systolic fraction.
`
`Table 2. Proposed formulas for the estimation of left
`ventricular filling pressure.
`
`MFV and PVF (for patients in sinus rhythm+left ventricular
`systolic dysfunction)
`PCWP=1.85 x deceleration rate — 0.1 x SF+ 10.9 [' °1
`MFV and colour M-mode (for patients in sinus rhythm and
`various cardiac conditions)
`PCWP 527 x (EIPv)+4.661131
`MFV and TDI mitral annulus (for patients in sinus rhythm and
`various cardiac conditions)
`PCWP =1.9+ 1-24 x (E/E')t`'1
`MFV and TDI mitral annulus (for patients with single transmitral
`flow wave due to tachycardia)
`PCWP=1.55+1.47 x (E/E') 1 't
`MFV and TDI mitral annulus (for patients in atrial fibrillation)
`PCWP=6489+0.821 x (E/E') (2111
`
`MFV: mitral flow velocity; PVF: pulmonary vein flow; PCWP:
`pulmonary artery wedge pressure; TDI: tissue Doppler. See Table
`I for the other abbreviations.
`
`parameters used for the estimation of left ventricular
`filling pressure are summarized in Fig. 1. Table 1 shows
`parameters that can be used to identify patients with an
`elevated left ventricular filling pressure. The next step in
`the analysis of patients is to use formulas which provide
`an estimate of the actual filling pressure (Table 2).
`Two questions arise: (1) should left ventricular filling
`pressures be routinely estimated during the echocardio-
`graphic examination of patients with known or sus-
`pected heart failure? and (2), what indices should be
`used in a given patient? To answer the first question
`additional studies specifically designed to assess the
`practical impact of this non-invasive measurement on
`treatment and outcome are needed. We should realize,
`however, that in everyday practice we try to assess the
`haemodynamic status on the basis of symptoms and
`clinical signs despite the fact that the sensitivity of these
`indices in identifying patients with a high filling pressure
`is, at best, 60%[222 1 . Doppler echocardiography is far
`more accurate and reproducible, provided that an
`appropriate methodology is applied.
`As far as the method and the indices are concerned,
`we think that two concepts should be kept in mind. The
`first is that because of the complex pathophysiologic
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`Eur J Echocardiography, Vol. 3, issue 1, March 2002
`
`mechanisms that govern the relation between Doppler
`echocardiographic variables and left atrial pressures,
`no single variable can be used to assess left ventricular
`filling pressures in a given patient. Second, different
`methods should be applied in different subsets of
`patients, taking into consideration factors such as the
`etiology of the disease, heart rate and rhythm, and
`systolic function. We suggest beginning the evaluation of
`left ventricular filling pressure by looking at dimensions
`and function of the left ventricular by standard M- and
`B-mode echo. As stated above, if the left ventricle is
`dilated and its systolic function depressed the trans-
`mitral flow velocity parameters alone [61 or in combina-
`tion with pulmonary venous flow parameters 001 (Table
`2, first equation) are usually sufficient for estimating left
`ventricular filling pressure. If there are still doubts, or
`the pulmonary venous flow recording is technically
`inadequate, E/Pv or E/E' ratios can also be caclulated. If
`the left ventricular systolic function is normal or mildly
`depressed, the E/E' ratio is the measurement of choice. It
`allows differentiation of patients with normal (low left
`ventricular filling pressure) from those with pseudo-
`normal (high left ventricular filling pressure) mitral flow
`velocity pattern, those in whom an impaired filling is due
`to `restriction' from those in whom this is due to
``constriction' [231. In addition, E/E' ratio incorporated in
`different equations (Table 2) can be used to quantita-
`tively estimate left ventricular filling pressure in various
`subsets of patients such as those with a single transmitral
`flow due to sinus tachycardia, hypertrophic cardio-
`myopathy, cardiac allograft and atrial fibrillation ["-201 .
`The concepts presented will be exemplified by several
`patients who underwent simultaneous invasive and
`Doppler echocardiographic assessment.
`
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