a

Comprehensive imaging

All modalities included in the standard TTE evaluation inclusive of M-mode, 2D, and 3D where applicable, pulsed, color, continuous wave Doppler (CWD), and combined qualitative and quantitative assessment contribute to valve regurgitation assessment.

b

Integrative interpretation

While the predictive power for outcome of all the measurements is not equal and is dominated by a few powerful quantitative measures, interpretation should not rely on a single parameter. Single measures are subject to variability (anatomic, physiologic, and operator); a combination of measures and signs should be comprehensively used to describe and report the final assessment of valve regurgitation.

c

Individualization

Recent data show that valve regurgitation measures and signs that appear similar may have different implications in different etiologies, so that measures and signs require individualized interpretation, taking into account body size, cause of regurgitation, cardiac compliance and function, acuteness or chronicity of the regurgitation, regurgitation dynamics, and hemodynamic conditions at measurement, among others.

d

Precise language

Avoiding imprecision and including detailed and comprehensive observations of the cause, mechanism, severity, location, associated lesions, and cardiac response are required. This language should be standardized and concise. Table 1 summarizes the essential parameters needed in the evaluation of valvular regurgitation with echocardiography.

a

Valve structure and severity of regurgitation

Competent leaflets are characterized by a sufficient coaptation surface, which approximates 8-10 mm for the mitral valve (MV), 4-9 mm for the TV, and a few millimeters for semilunar valves. Measurement of leaflet coaptation surface is not accurate with TTE. Three-dimensional TEE or other imaging modalities may allow a prediction of regurgitation severity based on leaflet coaptation. Severe regurgitant lesions when noted represent direct signs of large regurgitant orifices. Such lesions occur in various etiologies: large perforations, large flail segments, profound retraction of leaflets leaving a coaptation gap, or marked tenting of leaflets with tethering and loss of coaptation. All of these findings predict severe valve regurgitation with a high positive predictive value but low sensitivity. Hence, these specific signs are useful when present, but their absence does not exclude severe regurgitation. TTE is the main modality to assess valvular structure usually with the 2D approach, with TEE reserved for inconclusive studies, and to assess eligibility and suitability for transcatheter or surgical procedures. Three-dimensional applications in evaluating valve morphology have had a significant impact on the accuracy of localization of valvular lesions mostly from the transesophageal approach, particularly for the atrioventricular valves. The current lower spatial and temporal resolution of 3D TTE limits its evaluation of valvular structure, however, this is improving.

b

Impact of regurgitation on cardiac remodeling

As blood is incompressible, the regurgitant volume (RVol) must be contained in the cardiac cavities affected, implying that some degree of cavity dilation is proportional to the severity and chronicity of regurgitation. Despite this obligatory remodeling, the dilatation of cardiac cavities is considered in general a supportive sign of valvular regurgitation severity and not a specific sign (unless some conditions are met) because of multiple factors affecting cardiac remodeling. Acute severe regurgitation is characterized by a large regurgitant orifice, but cavity dilatation is minimized. The kinetic energy transmitted through the regurgitant orifice is affected by low cavity compliance, whereby the regurgitant energy is transformed into potential energy (elevated pressure in the receiving chamber) so that rapid equalization of pressure occurs with a low driving force for regurgitation. Consequently, acute severe regurgitation may be brief, with low RVol (low kinetic energy) and little cavity dilatation. In chronic regurgitation, however, cavity dilatation should reflect the regurgitation severity and duration. Cavity dilatation may be specific for significant regurgitation when ventricular function is preserved but loses specificity in conditions such as cardiomyopathy or ischemic ventricular dysfunction. A component of intrinsic dilatation (e.g., cardiomyopathy, atrial dilatation due to atrial fibrillation) may exaggerate the apparent “consequences” of regurgitation. Conversely, in patients with small cavities prior to the onset of regurgitation, an increase in cavity size may be underestimated if preregurgitation cavity size is unknown. Anatomic variability and technical issues may limit the ability to detect cavity dilatation. Measuring cavity diameters rather than volumes has inherent limitations as the diameter-volume relationship is nonlinear. Furthermore, the proposed range of normal values currently available is based on a limited number of subjects, so that for patients with small or very large body size, normalcy is difficult to define. The small body size limitation is of particular concern in evaluating valve regurgitation in females, where normalizing ventricular and regurgitant measurements to body size may provide a more accurate assessment of outcomes. Nevertheless, in a patient with regurgitation, an enlarged ventricle is consistent with significant regurgitation in the chronic setting and in the absence of other modulating factors, particularly when ventricular function is normal. Once a diagnosis of significant regurgitation is established, serial echocardiography with TTE is currently the method of choice to assess the progression of the impact of regurgitation on cardiac chamber structure and function. Careful attention to consistency of measurements and individualized interpretation of results are critical to the assessment of cardiac remodeling as a sign of regurgitation severity. Contrast echocardiography should be used in technically difficult studies for better endocardial visualization, as it enhances overall accuracy of ventricular volume measurements. Three-dimensional TTE can also be used for an overall more accurate assessment of volumes and ejection fraction, as it avoids foreshortening of the left ventricle (LV).

Echocardiography in general tends to underestimate measurements of LV volumes compared to other techniques when the traced endocardium includes ventricular trabeculations; the use of contrast to better visualize the endocardial borders excludes trabeculations and provides larger measurements of cavity size, closer to those by computed tomography and CMR.

a

Jet characteristics and jet area

Since color Doppler visualization of regurgitant jets plays such a significant role in the assessment of valvular regurgitation, it is useful to discuss the underlying basis of color jet formation and display and factors that affect it. A more detailed exposition on color jet formation has been described elsewhere. First, it is important to understand that simply knowing the orifice flow rate is not enough to predict jet size, since the jet will entrain additional flow as it propagates into the receiving chamber and this entrainment strongly depends on the orifice velocity (which in turn is affected by the orifice driving pressure). Rather, jet flow is governed mainly by conservation of momentum. Cardiologists are likely less familiar with momentum as opposed to the other two conserved quantities in fluid flow: mass (manifest in the continuity equation) and energy (found in the Bernoulli equation); but momentum is a critical concept for understanding regurgitant jets. For a jet originating through a regurgitant orifice with effective orifice area A and velocity v , the flow Q is equal to Av , and the momentum M is given by Qv or Av. ² (By extension, energy is given by Qv ² or Av ³ ). The amount of momentum that is within a jet at its orifice remains constant throughout the jet. Thus, a 5 m/sec mitral regurgitation (MR) jet with a flow rate of 100 mL/sec should appear the same by color Doppler as a 2.5 m/sec tricuspid regurgitation (TR) jet with a flow rate of 200 mL/sec. For a free turbulent jet, the centerline velocity in the jet drops off inversely with distance from the regurgitant orifice.

To understand how large a jet will appear in color Doppler, one needs to know the minimum velocity that can be detected by the instrument. This is not specifically defined on the echocardiogram but typically is a fraction (around 10%) of the full Nyquist velocity. The jet will appear anywhere the jet velocity is greater than this minimally detectible velocity. The situation is somewhat more complicated in that no jets inside the heart are completely free but are constrained by the chamber walls, causing the velocity to fall off earlier than it would otherwise. The effect of the interplay among momentum, chamber constraint, and minimal displayed velocity on jet area is complex, but for clinical purposes, it suffices to know the following determinants of jet size ( Table 2 ):

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  Jet momentum ( Av ² ): a major overall determinant of jet size.

  
  
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  Jet constraint/wall impingement: eccentric wall-hugging jets lose momentum rapidly, thus appearing smaller than nonconstrained jets of the same RVol.

  
  
• •
  

  Nyquist limit (velocity scale): reducing the velocity scale emphasizes lower velocities and makes the jet appear larger. In addition, blood cells within the receiving chamber that move in response to or are entrained by the regurgitant jet may reach the minimal velocity and thus appear part of the regurgitant jet.

  
  
• •
  

  Orifice geometry: slit-like orifices (particularly imaged along the long axis of the orifice) and multiple separate orifices lead to larger jets than single, relatively round orifices.

  
  
• •
  

  Pulse repetition frequency (PRF): affects jet area inversely

  
  
• •
  

  Doppler gain: jet size is quite sensitive and proportional to gain.

  
  
• •
  

  Ultrasound attenuation: attenuation in the far field, from body habitus, or from an interposing highly reflectant structure such as calcium or metal (interferes with both imaging and Doppler) will decrease jet size.

  
  
• •
  

  Transducer frequency: this has a dual effect. The higher frequency experiences a significant Doppler shift at lower velocities, making jets larger, such as in TEE. On the other hand, these higher frequency beams suffer excessive attenuation and jets may appear smaller in the far field, during TTE.

  
  
• •
  

  Angle of interrogation: since color Doppler is sensitive only to the component of flow in the direction of the transducer, jets interrogated orthogonally may appear smaller than the same jet imaged axially. This effect actually is lessened as the turbulence within jets leads to high-velocity flow in all directions, thus making the jet visible even when imaged from the side.

  
  
• •
  

  Color versus tissue threshold: if the tissue priority is set too high, structures may encroach on the color Doppler signal.

Thus, a larger area of a jet that is central in the cavity may imply more regurgitation, but as discussed, sole reliance on this parameter can be misleading. Figure 2 illustrates examples of modifiers of jet size. Standard technique is to use a Nyquist limit (aliasing velocity [Va]) of 50-70 cm/sec and a high color gain that just eliminates random color speckle from nonmoving regions ( Figure 2 ). Eccentric wall-impinging jets appear significantly smaller than centrally directed jets of similar hemodynamic severity. Their presence however, should also alert to the possibility of structural valve abnormalities (e.g., prolapse, flail, or perforation), frequently situated in the leaflet or cusp opposite to the direction of the jet. A jet may appear larger by increasing the driving pressure across the valve (higher momentum); hence the importance of measuring blood pressure for left heart lesions at the time of the study, particularly in the intraoperative setting or in a sedated patient. Lastly, it is important to note that in cases of very large regurgitant orifice areas, such as in cases of massive TR with a wide, noncoapting valve, a distinct jet may not be seen with color Doppler because of laminar flow and very low blood velocity.

Effect of color gain, Nyquist limit, and transducer frequency on color jet area. Color gain should be optimized high, just below clutter noise level, otherwise the jet will be much smaller. A low Nyquist limit will emphasize lower velocities, and thus the jet will be larger; Nyquist should be between 50 and 70 cm/sec. A higher transducer frequency, as used in TEE, will also depict a slightly larger jet.

b

Vena contracta

The vena contracta (VC) is the narrowest portion of the regurgitant flow that occurs at or immediately downstream of the regurgitant orifice ( Figure 1 ). It is characterized by high-velocity laminar flow and is slightly smaller than the anatomic regurgitant orifice (ARO). Thus, the cross-sectional area (CSA) of the VC represents a measure of the effective regurgitant orifice area (EROA), a true parameter of lesion severity. The size of the hydraulic VC is independent of flow rate and driving pressure for a fixed orifice. However, if the regurgitant orifice is dynamic, the VC may change during the cardiac cycle. In general, the VC by color Doppler significantly overestimates the hydraulic VC and is dependent on flow rate, likely because of entrainment. Despite these limitations, it remains a helpful semiquantitative measure of valve regurgitation severity. The VC by color Doppler is considerably less dependent on technical factors (e.g., PRF) compared with the jet extent. Imaging of the VC can be achieved using 2D or 3D color-flow Doppler, each presenting different challenges. For 2D VC measurement, it is indispensable to have a linear view of the three components of regurgitant flow (flow convergence, VC, jet area) and to orient the ultrasonic beam as perpendicular to the flow as possible to take advantage of axial measurement accuracy. Hence, it is often necessary to angulate the transducer out of the conventional echocardiographic imaging planes. Proper beam-flow orientation is best achieved for aortic or pulmonary regurgitation (PR), less for MR, and even less for TR. A zoomed view is also indispensable to minimize the measurement inaccuracies for a width of a few millimeters. VCA tracing requires 3D imaging and is achieved offline by reorienting images and using cropping planes to locate the VC. The color flow sector should also be as narrow as possible, to maximize lateral and temporal resolution. Achieving reasonable certainty that the smallest flow area is traced is a tedious process and may be difficult and lengthy; automated processes are being developed to this end. Because of the small values of the width of the VC (usually <1 cm), small errors in its measurement may lead to a large percent error and misclassification of the severity of regurgitation, hence the importance of accurate acquisition of the primary data and measurements.

c

Flow convergence

Locating the flow convergence proximal to the regurgitant orifice provides qualitative information on both the location of the lesion causing the regurgitation and the magnitude of the regurgitant flow. A well-defined small flow convergence combined with a small jet is specific for mild regurgitation, while a large flow convergence recorded at the minimum 50-70 cm/sec range, persisting throughout the duration of flow is specific for severe regurgitation. Flow convergence is amenable to quantitation of regurgitant flow (see below).

a

Forward flow

Valve regurgitation implies that the forward stroke volume (SV) across the affected valve during the cardiac cycle is increased. For atrioventricular valves, increased forward flow is characterized by increased early E velocity and E/A ratio, generally associated with a short E deceleration time in the absence of stenosis. This supportive sign is mired by the multiple factors affecting ventricular filling including diastolic function, ventricular inflow obstruction (e.g., annular calcification), or alterations in cardiac output. For semilunar valves, ejection velocity is slightly increased with severe regurgitation, but the velocity time integral (VTI) of forward flow at the annulus is generally increased along with a prolongation in ejection time. This supportive sign is nonspecific but is a useful part of the constellation of findings in severe regurgitation.

b

Flow reversal

The RVol, when significant, may cause flow reversal in the receiving or proximal chamber, depending on the valve. In atrioventricular valves, valve regurgitation may result in pulmonary systolic venous flow reversal with MR or hepatic venous systolic flow reversal in cases of TR. Such systolic reversals are considered specific (>85% probability of severe regurgitation when present) but insensitive. Care should be taken to exclude other causes of flow reversal such as atrioventricular dissociation or pacemakers with ventriculoatrial conduction. For aortic regurgitation (AR), reversal of flow is diastolic, noted in the aortic arch and abdominal aorta, and is influenced by multiple factors, particularly peripheral vascular resistance and aortic compliance. Hence, prominent holodiastolic aortic flow reversal is a specific sign of severe AR but insensitive. Other causes of diastolic flow reversal should be sought in the absence of AR such as arteriovenous fistulas, ruptured sinus of Valsalva, or patent ductus arteriosus.

a

Spectral density

The intensity (amplitude) of the returned Doppler signal is proportional to the number of red blood cells reflecting the signal. Hence, the signal density of the CWD of the regurgitant jet should reflect the regurgitant flow. Thus a faint, incomplete, or soft signal is indicative of trace or mild regurgitation. A dense signal may not be able to differentiate moderate from severe regurgitation. Signal density also depends on spectral recording of the jet throughout the relevant portion of the cardiac cycle. Therefore, a central jet well aligned with the ultrasound beam may appear denser than an eccentric jet of much higher severity, if not well aligned.

b

Timing of regurgitation

The duration and timing of regurgitation can be valuable in the overall assessment of the physiology and hemodynamics of regurgitation. While the majority of regurgitant lesions are holosystolic or holodiastolic, some may occur during a brief period ( Figure 3 ). In patients with MV prolapse (MVP), the regurgitation may be limited to late systole and is rarely severe when not holosystolic, with infrequent cardiac remodeling. MR and TR may be limited to isovolumic contraction and relaxation phases or both, particularly in functional regurgitation, which correspond to mild or trivial regurgitation.

M-mode color images depict timing of MR: classic holosystolic MR, late systolic MR due to MVP, and early systolic MR in a patient with cardiomyopathy and left bundle branch block. Single-frame measurements of EROA or VC (width or area) will overestimate MR severity when it is not holosystolic.

c

Time course of the regurgitant velocity

The spectral velocity profile of a regurgitant jet is determined by the pressure difference between the upstream and downstream chambers, with a general parabolic shape during systole for atrioventricular valves and a trapezoid shape during diastole for semilunar valves. For atrioventricular valves, an early peaking or cutoff sign denotes a large regurgitant wave in the respective atrium and significant regurgitation. A rapid decay of the diastolic slope in semilunar valve regurgitation also can denote significant regurgitation but is exaggerated in cases of poor ventricular compliance and thus may not be specific. Pulmonic regurgitation (PR) may end prior to end diastole and may be related to poor ventricular compliance and/or severe regurgitation. Premature termination of diastolic flow is rarely seen in AR and usually denotes acute severe regurgitation.

a

Quantitative pulsed Doppler method

Doppler recording of VTI can be combined with 2D or 3D measurement of flow area to derive SVs at different sites. The difference between inflow and outflow SVs of the same ventricle is caused by the RVol in single valvular regurgitation. This method is simple in principle, however, accurate results require individual training (e.g., practice in normal patients where SVs at different sites are equal). Briefly, forward SV at any valve annulus—the least variable anatomic area of a valve apparatus—is derived as the product of CSA and the VTI, measured by pulsed Doppler at the annulus. Overall, assumption of a circular geometry has worked well clinically. In this case,

Calculations of SV can be made at two or more different sites: left ventricular outflow tract (LVOT), mitral annulus and right ventricular outflow tract (RVOT). In the absence of regurgitation, SV determinations at these sites are equal. In the presence of regurgitation of one valve, without the presence of any intracardiac shunt, the SV through the affected valve is larger than through the other competent valves. The difference between the two represents the RVol ( Figure 4 ). RF is then derived as the RVol divided by the SV through the regurgitant valve. Thus,

Echo-Doppler calculations of SV at the LVOT and MV annulus sites. In this example of severe MR, SV _MV was 183 mL (d = 3.5 cm, VTI = 19 cm) and SV _LVOT was 58 mL (d = 2.3 cm, VTI = 14 cm). This yielded an RVol of 125 mL and an RF of 125/183 or 68%. d, Diameter of the annulus; PW , pulsed wave Doppler.

EROA can be calculated using the VTI of the regurgitant jet (VTI _RegJet ) recorded by CWD as

All measurements are expressed in centimeters or milliliters, leading to the calculation of EROA in square centimeters.

The most common errors encountered in determining these parameters are (1) failure to measure the valve annulus accurately (error is squared in the formula), (2) failure to trace the modal velocity (brightest signal representing the velocity of the majority of blood cells) of the pulsed Doppler tracing, and (3) failure to position the sample volume correctly, and with minimal angulation, at the level of the annulus. Furthermore, in the case of significant calcifications of the mitral annulus and valve, quantitation of flow at the mitral site is less accurate and more prone to errors.

A major challenge with all volumetric methods is that each of the component SVs has intrinsic error, in part due to the multiple parameters that must be combined into each one. These errors increase (as the root sum square) when the SVs are subtracted, with the relative error increasing even more as one subtracts one large number from another to get a small RVol. For example, a recent study of 3D color flow quantitation demonstrated 95% confidence limits of mitral flow (relative to CMR) of ±18.9 mL and ±17.8 mL for the aortic valve. When these SVs are subtracted, the confidence intervals rise to ±26 mL, emphasizing the critical need for meticulous attention to technique with these methods.

b

Quantitative volumetric method

Because blood is incompressible, the total SV ejected by the ventricle in single-valve regurgitation is equal to the SV at the regurgitant valve (SV _RegValv ). If the forward SV (SV _Forward ) is measurable simultaneously by Doppler or by any other method, the RVol can be calculated. Most use of this method has been for single left-sided regurgitant valves and the LV SV has been calculated using 2D echocardiography measurement of LV volumes. In such cases SV _Forward is measured on the nonregurgitant valve (aortic valve for MR or MV for AR). Hence calculations are the following:

Methods for calculation of LV volumes by echocardiography have been previously detailed. The limitation of the method is the potential pitfall of underestimating true LV volume as noted above and therefore underestimating regurgitation severity. This can be improved with avoidance of foreshortening and use of contrast echocardiography. Assessment of ventricular volumes based on M-mode measurements has important limitations and is not recommended. The use of 3D echocardiography may improve the accuracy of LV volume determinations.

c

Flow convergence method (proximal isovelocity surface area [PISA] method)

In valvular regurgitation, blood flow converges towards the regurgitant orifice forming concentric, roughly hemispheric shells of increasing velocity and decreasing surface area. Color flow mapping offers the ability to image one of these hemispheres that corresponds to the first aliasing threshold (where the displayed color changes from red to yellow) as one moves out from the regurgitant orifice. This is generally done by shifting the baseline of the color scale in the direction of the regurgitant jet (i.e., down for MR into the LA on TTE and up for MR on TEE) to highlight an aliasing contour where flow convergence has a roughly hemispheric shape; it may appear more teardrop-shaped because lateral flows, perpendicular to the ultrasound beam, cannot be detected by Doppler. Alternatively, one could reduce the PRF to decrease the Nyquist (and aliasing) velocity, although most echocardiographers prefer shifting the baseline. The radius of the PISA is measured from the point of color Doppler aliasing (abrupt change in color from blue to yellow if jet direction is away from transducer) to the VC. Regardless, the aliasing contour is better detected if variance color mapping is turned off. For a hemispheric proximal convergence zone with radius r , the regurgitant flow rate (RFlow, in mL/sec) is calculated as the product of the surface area of the hemisphere (2π r ² ) and the Va as

Assuming that the selected PISA radius occurs at the time of peak regurgitant velocity, the EROA at that specific time is derived as

The PISA method is simple conceptually and in its practical calculation ( Figure 5 ). It allows a qualitative and a quantitative assessment of the severity of the regurgitation and has become the main method of quantification of regurgitation, particularly on the mitral and TVs. However, there are several core principles to pay attention to in order to maintain quality control:

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  Timing of measurements: since the PISA calculation provides an instantaneous peak flow rate, the EROA calculated by this approach may not be equivalent to the average regurgitant orifice throughout the regurgitant phase. Previous studies using timed measurement in MR have shown that the regurgitation is often dynamic; two important precautions were highlighted : first, measurement of flow and velocity should be performed at simultaneous moments of the regurgitant phase ( Figure 5 ; e.g., not combining a late-systolic flow convergence with a midsystolic velocity). Second, the PISA measurement most representative of the mean EROA is that performed simultaneously with the peak velocity of the regurgitation ( Figure 5 ). Hence it is essential to follow these rules without aiming for the largest flow convergence, while also remembering that the dynamic nature of the jets may lead to underestimation in the case of typically bimodal secondary MR or overestimation in the case of late systolic primary MR.

  
  
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  Duration of regurgitation: the issue of instantaneous versus average measurement comes particularly into play for “partial” regurgitation (e.g., myxomatous MR confined to mid-late systole or functional MR in early systole and isovolumic relaxation). For such partial regurgitation, the RVol can be approximated by multiplying the maximal EROA by the VTI from the densest part of the CWD tracing. When reporting the EROA, however, it is best to use the “mean” EROA, where the maximal EROA is normalized by the proportion of systole during which significant regurgitation occurs; preferably, the RVol should be retained as the most appropriate index. Where feasible, volumetric methods can yield these regurgitant parameters without needing to make assumptions about variation in the EROA.

  
  
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  Shape of PISA: the standard method assumes that the valvular plane from which the regurgitant orifice arises is planar and that the flow convergence is homogeneous, but this is not always the case. First, the plane of the regurgitant orifice may be conical rather than flat or planar (180°), as seen in TR and MV leaflet tenting. This conical angle should be accounted for, as the flow convergence covers more than a hemisphere. Second, the shape of the flow convergence may be inconsistent with a hemisphere, which may require adjustment of the Va such that a well-defined hemisphere is shown. If the flow convergence does not fulfill the criteria of a hemisphere due to constraint, the initial approach is to attempt avoiding the constraint by increasing the Va, making the flow convergence smaller and less prone to constraint. However, if the constraint persists, the echocardiographer should decide whether a simple angle correction for the truncation of the flow convergence is possible, and if not, the method should not be reported.

  
  
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  Shape of the regurgitant orifice: a factor that complicates PISA calculations is the shape of the regurgitant orifice itself. While organic disease (e.g., leaflet flail) usually causes a roughly circular orifice, the regurgitant orifice area in functional disease is often elongated throughout the coaptation line. Application of the standard PISA formula to such an elliptical orifice will lead predictably to flow underestimation. Recent computational fluid dynamics simulations have shown that this underestimation may not be as severe as might be feared, depending on the shape of the ellipse, since the flow contours rapidly become hemispheric as one moves away from the orifice. For a 3:1 ellipse, use of the standard PISA formula (with 40 cm/sec Va and 5 m/sec orifice velocity) only results in 8% underestimation relative to a circular orifice. However, a 5:1 ratio leads to a 17% underestimation, and a 10:1 ratio to a 35% underestimation.

Schematic representation of the flow convergence method (PISA). The example on the right shows the measurement of the PISA radius and the timing of the selection of the color frame for measurement ( solid yellow arrow ), corresponding to the maximal jet velocity by CWD ( dashed arrow ). Reg , Regurgitation; PKV , peak velocity of regurgitant flow by CWD; VTI , velocity time integral of the regurgitant jet by CWD.

A few additional limitations of PISA should be noted. Central jets allow an easy alignment of the ultrasound beam and the centerline of the flow convergence. In contrast, eccentric jets may present a challenge, for both flow convergence and CWD recording (angulation or inability to record jet despite multiple windows). It is generally easy to identify the aliasing line of the hemispheric contour, but deciding on the position of the regurgitant orifice is more challenging. The presence of dark zones indicating horizontal flow perpendicular to the beam of ultrasound represents the best marker of the position of the regurgitant orifice ( Figure 5 ). In cases where this is not obvious, a display of simultaneous color and noncolor 2D images or turning off the color-flow imaging may be helpful. In cases where the regurgitant orifice is noncircular, as frequently is seen in functional MR (crescent shape), the PISA shape is also modified and no longer hemispheric. Three-dimensional color flow would provide a better assessment of the PISA surface (likely underestimated with 2D PISA), although with additional limitations of lower spatial and temporal resolution. Lastly, in patients with multiple jets, the PISA method can be applied to each orifice, with flows and EROA added together; if one lesion is very mild, it can be neglected. Overall, the PISA method by the combination of both qualitative visual assessment and full calculation is the most used method for quantitation of valvular regurgitation in routine clinical practice.

a

Ventricular volumes

When performing planimetry, it is important to draw the LV and RV end-diastolic and end-systolic contours on the phases with the largest and smallest blood volume, respectively.

b

Correct placement of the basal ventricular short-axis slice is critical

It is recommended that the most basal slice be located immediately on the myocardial side of the atrioventricular junction at end diastole. As a result of systolic motion of the MV toward the apex, a slice containing LV blood volume at end diastole may include only left atrium (LA) without LV blood volume at end systole. The LA can be identified when less than 50% of the blood volume is surrounded by myocardium and the blood volume cavity is seen to be expanding during systole. It can be helpful to use analysis software that allows adjustment for systolic atrioventricular ring descent using cross-referencing from long-axis locations. The RV contouring is performed in an analogous manner, with the RVOT volume included in the RV end-diastolic volume. Because of the tomographic nature of the technique, CMR can provide these volumetric measures in a 3D fashion without the need for geometric assumptions—in fact, it is considered the gold standard, with demonstrated accuracy and high reproducibility.

c

Planimetry of LV epicardial contour

This can be performed to derive LV mass.

d

Left atrial volume

LA volume can be derived by performance of multiple short-axis slices through the LA or by utilizing the biplane area-length method as in echocardiography.

It is important to note that normal reference ranges for left and right cardiac chamber volumes by CMR are higher than for echocardiography and that correlation between the two modalities is improved with use of 3D echocardiography and/or administration of echocardiographic contrast. The ability to image in any plane makes CMR robust for assessment of valvular anatomy and aids in assessment of mechanism of regurgitation. This can be especially useful for assessment of right-sided valves, which may be difficult to visualize by echocardiography. Assessment of valve anatomy is accomplished by performing a series of contiguous (no gap) parallel thin slice (4-5 mm) SSFP cine acquisitions in the plane of interest. The exact planes to be chosen for each valve will be described in detail in subsequent sections.

a

Phase-contrast CMR

This is the imaging sequence of choice in quantifying flow and calculating velocities. Protons moving along a magnetic field gradient acquire a phase shift relative to stationary spins. The phase shift is directly proportional to the velocity of the moving protons in a linear gradient. Phase-contrast CMR produces two sets of images: magnitude images and phase velocity maps ( Figure 7 ). The magnitude image is used for anatomic orientation of the imaging slice and to identify the boundaries of the vessel imaged. The phase map encodes the velocities within each pixel. Using both images, a region of interest can be traced at each time frame of the data set. The region of interest must be drawn carefully for each frame of the cardiac cycle because of movement and deformation of the vessel. Flow is derived by integrating the velocity of each pixel and its area over the cardiac cycle, allowing for calculation of anterograde and retrograde flows through a region of interest ( Figure 7 ). CMR flow measurements have extensive validation in both in vitro and in vivo studies.

CMR technique for assessment of great vessel forward and retrograde flow. Left side of the figure demonstrates a phase-contrast acquisition performed in the aortic root. This produces a set of two cine images at matched anatomic locations that provide differing information: a magnitude image that provides anatomic reference ( A ) and velocity or phase map with pixel values linearly related to velocity and direction of flow ( B ). On postprocessing, via drawing a region of interest around the aortic root ( red circles ), a flow versus time graph is generated ( C ), which can be used to compute forward ( red arrow ) and reverse flow ( yellow arrow ). In this example of AR, the reverse flow represents the directly measured volume of AR. The right side of the figure demonstrates the same, performed at the PA trunk to derive PA flow.

b

Quantitative methods

Methods for quantification of valvular regurgitation can be broadly divided into direct and indirect methods. The direct method employs use of through-plane phase-contrast CMR to quantify blood flow at any given location. This method has been shown to be very accurate for assessing anterograde and retrograde flow across semilunar valves and therefore is the preferred technique used for assessing aortic or pulmonic insufficiency. Phase contrast for direct assessment of flow in the mitral or TVs is more difficult because of significant motion of the annulus during systole. For this reason, quantification of mitral or tricuspid RVol is performed using an alternative, indirect approach by comparing ventricular SV (derived by planimetry of short-axis cines) to forward flow (derived by phase-contrast CMR) across the aortic or pulmonary valves (PVs; Figure 8 ). In addition to the preferred methods for each valve lesion described above, multiple additional indirect methods such as comparison of LV and RV SVs or use of mitral or tricuspid diastolic inflow can be employed to serve as an internal check.

Example CMR method for quantification of MR. The volume of the LV is calculated during end-diastole (LVEDV) and during end-systole (LVESV) via the methodology demonstrated in Figure 6 . The total volume of blood ejected from the LV, LV SV, is computed as the difference between LV end-diastolic volume and LV end-systolic volume. In this example LV SV is 150 mL. The volume of blood crossing the aortic (AO) valve is measured by performance of a phase-contrast acquisition in the aorta (as detailed in Figure 6 ); in this example, 80 mL. The mitral RVol (M RVol) is computed as the difference between the LV SV and aortic forward SV; in this example, 70 mL.

c

Technical considerations

When performing flow measurements a few technical aspects need to be kept in mind. The velocity encoding should be set to the lowest velocity feasible without aliasing. It is important that the imaging plane be (1) centered in the vessel of interest, (2) aligned orthogonally to the expected main blood flow direction in two spatial directions, and (3) centered in the isocenter of the magnetic field. Despite these steps, phase offset errors due to eddy currents in the magnetic field can still occur, and it is important to consider the use of phantom or background correction in every case if possible.

d

Thresholds for regurgitation severity

There is a paucity of data on specific CMR thresholds of RVol or fraction that define severe regurgitation based on outcomes. An earlier study suggested using a RF threshold of 48% by CMR to define severe regurgitation of the aortic or MVs, based on achieving the best correlation with limited echocardiographic assessment. One study in MR and another in AR have focused on RVol/fraction thresholds for prognosis. Progression to symptoms and need for valve surgery were seen with a RF of >40% for MR and >33% for AR (or >55 mL). Due to the paucity of data and absence of other recommendations, the general cutoffs for RVols and RFs recommended by echocardiography and the recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines are used.

a

Comprehensive imaging

All modalities included in the standard TTE evaluation inclusive of M-mode, 2D, and 3D where applicable, pulsed, color, continuous wave Doppler (CWD), and combined qualitative and quantitative assessment contribute to valve regurgitation assessment.

b

Integrative interpretation

While the predictive power for outcome of all the measurements is not equal and is dominated by a few powerful quantitative measures, interpretation should not rely on a single parameter. Single measures are subject to variability (anatomic, physiologic, and operator); a combination of measures and signs should be comprehensively used to describe and report the final assessment of valve regurgitation.

c

Individualization

Recent data show that valve regurgitation measures and signs that appear similar may have different implications in different etiologies, so that measures and signs require individualized interpretation, taking into account body size, cause of regurgitation, cardiac compliance and function, acuteness or chronicity of the regurgitation, regurgitation dynamics, and hemodynamic conditions at measurement, among others.

d

Precise language

Avoiding imprecision and including detailed and comprehensive observations of the cause, mechanism, severity, location, associated lesions, and cardiac response are required. This language should be standardized and concise. Table 1 summarizes the essential parameters needed in the evaluation of valvular regurgitation with echocardiography.

a

Valve structure and severity of regurgitation

Competent leaflets are characterized by a sufficient coaptation surface, which approximates 8-10 mm for the mitral valve (MV), 4-9 mm for the TV, and a few millimeters for semilunar valves. Measurement of leaflet coaptation surface is not accurate with TTE. Three-dimensional TEE or other imaging modalities may allow a prediction of regurgitation severity based on leaflet coaptation. Severe regurgitant lesions when noted represent direct signs of large regurgitant orifices. Such lesions occur in various etiologies: large perforations, large flail segments, profound retraction of leaflets leaving a coaptation gap, or marked tenting of leaflets with tethering and loss of coaptation. All of these findings predict severe valve regurgitation with a high positive predictive value but low sensitivity. Hence, these specific signs are useful when present, but their absence does not exclude severe regurgitation. TTE is the main modality to assess valvular structure usually with the 2D approach, with TEE reserved for inconclusive studies, and to assess eligibility and suitability for transcatheter or surgical procedures. Three-dimensional applications in evaluating valve morphology have had a significant impact on the accuracy of localization of valvular lesions mostly from the transesophageal approach, particularly for the atrioventricular valves. The current lower spatial and temporal resolution of 3D TTE limits its evaluation of valvular structure, however, this is improving.

b

Impact of regurgitation on cardiac remodeling

As blood is incompressible, the regurgitant volume (RVol) must be contained in the cardiac cavities affected, implying that some degree of cavity dilation is proportional to the severity and chronicity of regurgitation. Despite this obligatory remodeling, the dilatation of cardiac cavities is considered in general a supportive sign of valvular regurgitation severity and not a specific sign (unless some conditions are met) because of multiple factors affecting cardiac remodeling. Acute severe regurgitation is characterized by a large regurgitant orifice, but cavity dilatation is minimized. The kinetic energy transmitted through the regurgitant orifice is affected by low cavity compliance, whereby the regurgitant energy is transformed into potential energy (elevated pressure in the receiving chamber) so that rapid equalization of pressure occurs with a low driving force for regurgitation. Consequently, acute severe regurgitation may be brief, with low RVol (low kinetic energy) and little cavity dilatation. In chronic regurgitation, however, cavity dilatation should reflect the regurgitation severity and duration. Cavity dilatation may be specific for significant regurgitation when ventricular function is preserved but loses specificity in conditions such as cardiomyopathy or ischemic ventricular dysfunction. A component of intrinsic dilatation (e.g., cardiomyopathy, atrial dilatation due to atrial fibrillation) may exaggerate the apparent “consequences” of regurgitation. Conversely, in patients with small cavities prior to the onset of regurgitation, an increase in cavity size may be underestimated if preregurgitation cavity size is unknown. Anatomic variability and technical issues may limit the ability to detect cavity dilatation. Measuring cavity diameters rather than volumes has inherent limitations as the diameter-volume relationship is nonlinear. Furthermore, the proposed range of normal values currently available is based on a limited number of subjects, so that for patients with small or very large body size, normalcy is difficult to define. The small body size limitation is of particular concern in evaluating valve regurgitation in females, where normalizing ventricular and regurgitant measurements to body size may provide a more accurate assessment of outcomes. Nevertheless, in a patient with regurgitation, an enlarged ventricle is consistent with significant regurgitation in the chronic setting and in the absence of other modulating factors, particularly when ventricular function is normal. Once a diagnosis of significant regurgitation is established, serial echocardiography with TTE is currently the method of choice to assess the progression of the impact of regurgitation on cardiac chamber structure and function. Careful attention to consistency of measurements and individualized interpretation of results are critical to the assessment of cardiac remodeling as a sign of regurgitation severity. Contrast echocardiography should be used in technically difficult studies for better endocardial visualization, as it enhances overall accuracy of ventricular volume measurements. Three-dimensional TTE can also be used for an overall more accurate assessment of volumes and ejection fraction, as it avoids foreshortening of the left ventricle (LV).

Echocardiography in general tends to underestimate measurements of LV volumes compared to other techniques when the traced endocardium includes ventricular trabeculations; the use of contrast to better visualize the endocardial borders excludes trabeculations and provides larger measurements of cavity size, closer to those by computed tomography and CMR.

a

Jet characteristics and jet area

Since color Doppler visualization of regurgitant jets plays such a significant role in the assessment of valvular regurgitation, it is useful to discuss the underlying basis of color jet formation and display and factors that affect it. A more detailed exposition on color jet formation has been described elsewhere. First, it is important to understand that simply knowing the orifice flow rate is not enough to predict jet size, since the jet will entrain additional flow as it propagates into the receiving chamber and this entrainment strongly depends on the orifice velocity (which in turn is affected by the orifice driving pressure). Rather, jet flow is governed mainly by conservation of momentum. Cardiologists are likely less familiar with momentum as opposed to the other two conserved quantities in fluid flow: mass (manifest in the continuity equation) and energy (found in the Bernoulli equation); but momentum is a critical concept for understanding regurgitant jets. For a jet originating through a regurgitant orifice with effective orifice area A and velocity v , the flow Q is equal to Av , and the momentum M is given by Qv or Av. ² (By extension, energy is given by Qv ² or Av ³ ). The amount of momentum that is within a jet at its orifice remains constant throughout the jet. Thus, a 5 m/sec mitral regurgitation (MR) jet with a flow rate of 100 mL/sec should appear the same by color Doppler as a 2.5 m/sec tricuspid regurgitation (TR) jet with a flow rate of 200 mL/sec. For a free turbulent jet, the centerline velocity in the jet drops off inversely with distance from the regurgitant orifice.

To understand how large a jet will appear in color Doppler, one needs to know the minimum velocity that can be detected by the instrument. This is not specifically defined on the echocardiogram but typically is a fraction (around 10%) of the full Nyquist velocity. The jet will appear anywhere the jet velocity is greater than this minimally detectible velocity. The situation is somewhat more complicated in that no jets inside the heart are completely free but are constrained by the chamber walls, causing the velocity to fall off earlier than it would otherwise. The effect of the interplay among momentum, chamber constraint, and minimal displayed velocity on jet area is complex, but for clinical purposes, it suffices to know the following determinants of jet size ( Table 2 ):

• •
  

  Jet momentum ( Av ² ): a major overall determinant of jet size.

  
  
• •
  

  Jet constraint/wall impingement: eccentric wall-hugging jets lose momentum rapidly, thus appearing smaller than nonconstrained jets of the same RVol.

  
  
• •
  

  Nyquist limit (velocity scale): reducing the velocity scale emphasizes lower velocities and makes the jet appear larger. In addition, blood cells within the receiving chamber that move in response to or are entrained by the regurgitant jet may reach the minimal velocity and thus appear part of the regurgitant jet.

  
  
• •
  

  Orifice geometry: slit-like orifices (particularly imaged along the long axis of the orifice) and multiple separate orifices lead to larger jets than single, relatively round orifices.

  
  
• •
  

  Pulse repetition frequency (PRF): affects jet area inversely

  
  
• •
  

  Doppler gain: jet size is quite sensitive and proportional to gain.

  
  
• •
  

  Ultrasound attenuation: attenuation in the far field, from body habitus, or from an interposing highly reflectant structure such as calcium or metal (interferes with both imaging and Doppler) will decrease jet size.

  
  
• •
  

  Transducer frequency: this has a dual effect. The higher frequency experiences a significant Doppler shift at lower velocities, making jets larger, such as in TEE. On the other hand, these higher frequency beams suffer excessive attenuation and jets may appear smaller in the far field, during TTE.

  
  
• •
  

  Angle of interrogation: since color Doppler is sensitive only to the component of flow in the direction of the transducer, jets interrogated orthogonally may appear smaller than the same jet imaged axially. This effect actually is lessened as the turbulence within jets leads to high-velocity flow in all directions, thus making the jet visible even when imaged from the side.

  
  
• •
  

  Color versus tissue threshold: if the tissue priority is set too high, structures may encroach on the color Doppler signal.

Thus, a larger area of a jet that is central in the cavity may imply more regurgitation, but as discussed, sole reliance on this parameter can be misleading. Figure 2 illustrates examples of modifiers of jet size. Standard technique is to use a Nyquist limit (aliasing velocity [Va]) of 50-70 cm/sec and a high color gain that just eliminates random color speckle from nonmoving regions ( Figure 2 ). Eccentric wall-impinging jets appear significantly smaller than centrally directed jets of similar hemodynamic severity. Their presence however, should also alert to the possibility of structural valve abnormalities (e.g., prolapse, flail, or perforation), frequently situated in the leaflet or cusp opposite to the direction of the jet. A jet may appear larger by increasing the driving pressure across the valve (higher momentum); hence the importance of measuring blood pressure for left heart lesions at the time of the study, particularly in the intraoperative setting or in a sedated patient. Lastly, it is important to note that in cases of very large regurgitant orifice areas, such as in cases of massive TR with a wide, noncoapting valve, a distinct jet may not be seen with color Doppler because of laminar flow and very low blood velocity.

Effect of color gain, Nyquist limit, and transducer frequency on color jet area. Color gain should be optimized high, just below clutter noise level, otherwise the jet will be much smaller. A low Nyquist limit will emphasize lower velocities, and thus the jet will be larger; Nyquist should be between 50 and 70 cm/sec. A higher transducer frequency, as used in TEE, will also depict a slightly larger jet.

b

Vena contracta

The vena contracta (VC) is the narrowest portion of the regurgitant flow that occurs at or immediately downstream of the regurgitant orifice ( Figure 1 ). It is characterized by high-velocity laminar flow and is slightly smaller than the anatomic regurgitant orifice (ARO). Thus, the cross-sectional area (CSA) of the VC represents a measure of the effective regurgitant orifice area (EROA), a true parameter of lesion severity. The size of the hydraulic VC is independent of flow rate and driving pressure for a fixed orifice. However, if the regurgitant orifice is dynamic, the VC may change during the cardiac cycle. In general, the VC by color Doppler significantly overestimates the hydraulic VC and is dependent on flow rate, likely because of entrainment. Despite these limitations, it remains a helpful semiquantitative measure of valve regurgitation severity. The VC by color Doppler is considerably less dependent on technical factors (e.g., PRF) compared with the jet extent. Imaging of the VC can be achieved using 2D or 3D color-flow Doppler, each presenting different challenges. For 2D VC measurement, it is indispensable to have a linear view of the three components of regurgitant flow (flow convergence, VC, jet area) and to orient the ultrasonic beam as perpendicular to the flow as possible to take advantage of axial measurement accuracy. Hence, it is often necessary to angulate the transducer out of the conventional echocardiographic imaging planes. Proper beam-flow orientation is best achieved for aortic or pulmonary regurgitation (PR), less for MR, and even less for TR. A zoomed view is also indispensable to minimize the measurement inaccuracies for a width of a few millimeters. VCA tracing requires 3D imaging and is achieved offline by reorienting images and using cropping planes to locate the VC. The color flow sector should also be as narrow as possible, to maximize lateral and temporal resolution. Achieving reasonable certainty that the smallest flow area is traced is a tedious process and may be difficult and lengthy; automated processes are being developed to this end. Because of the small values of the width of the VC (usually <1 cm), small errors in its measurement may lead to a large percent error and misclassification of the severity of regurgitation, hence the importance of accurate acquisition of the primary data and measurements.

c

Flow convergence

Locating the flow convergence proximal to the regurgitant orifice provides qualitative information on both the location of the lesion causing the regurgitation and the magnitude of the regurgitant flow. A well-defined small flow convergence combined with a small jet is specific for mild regurgitation, while a large flow convergence recorded at the minimum 50-70 cm/sec range, persisting throughout the duration of flow is specific for severe regurgitation. Flow convergence is amenable to quantitation of regurgitant flow (see below).

a

Forward flow

Valve regurgitation implies that the forward stroke volume (SV) across the affected valve during the cardiac cycle is increased. For atrioventricular valves, increased forward flow is characterized by increased early E velocity and E/A ratio, generally associated with a short E deceleration time in the absence of stenosis. This supportive sign is mired by the multiple factors affecting ventricular filling including diastolic function, ventricular inflow obstruction (e.g., annular calcification), or alterations in cardiac output. For semilunar valves, ejection velocity is slightly increased with severe regurgitation, but the velocity time integral (VTI) of forward flow at the annulus is generally increased along with a prolongation in ejection time. This supportive sign is nonspecific but is a useful part of the constellation of findings in severe regurgitation.

b

Flow reversal

The RVol, when significant, may cause flow reversal in the receiving or proximal chamber, depending on the valve. In atrioventricular valves, valve regurgitation may result in pulmonary systolic venous flow reversal with MR or hepatic venous systolic flow reversal in cases of TR. Such systolic reversals are considered specific (>85% probability of severe regurgitation when present) but insensitive. Care should be taken to exclude other causes of flow reversal such as atrioventricular dissociation or pacemakers with ventriculoatrial conduction. For aortic regurgitation (AR), reversal of flow is diastolic, noted in the aortic arch and abdominal aorta, and is influenced by multiple factors, particularly peripheral vascular resistance and aortic compliance. Hence, prominent holodiastolic aortic flow reversal is a specific sign of severe AR but insensitive. Other causes of diastolic flow reversal should be sought in the absence of AR such as arteriovenous fistulas, ruptured sinus of Valsalva, or patent ductus arteriosus.

a

Spectral density

The intensity (amplitude) of the returned Doppler signal is proportional to the number of red blood cells reflecting the signal. Hence, the signal density of the CWD of the regurgitant jet should reflect the regurgitant flow. Thus a faint, incomplete, or soft signal is indicative of trace or mild regurgitation. A dense signal may not be able to differentiate moderate from severe regurgitation. Signal density also depends on spectral recording of the jet throughout the relevant portion of the cardiac cycle. Therefore, a central jet well aligned with the ultrasound beam may appear denser than an eccentric jet of much higher severity, if not well aligned.

b

Timing of regurgitation

The duration and timing of regurgitation can be valuable in the overall assessment of the physiology and hemodynamics of regurgitation. While the majority of regurgitant lesions are holosystolic or holodiastolic, some may occur during a brief period ( Figure 3 ). In patients with MV prolapse (MVP), the regurgitation may be limited to late systole and is rarely severe when not holosystolic, with infrequent cardiac remodeling. MR and TR may be limited to isovolumic contraction and relaxation phases or both, particularly in functional regurgitation, which correspond to mild or trivial regurgitation.

M-mode color images depict timing of MR: classic holosystolic MR, late systolic MR due to MVP, and early systolic MR in a patient with cardiomyopathy and left bundle branch block. Single-frame measurements of EROA or VC (width or area) will overestimate MR severity when it is not holosystolic.

c

Time course of the regurgitant velocity

The spectral velocity profile of a regurgitant jet is determined by the pressure difference between the upstream and downstream chambers, with a general parabolic shape during systole for atrioventricular valves and a trapezoid shape during diastole for semilunar valves. For atrioventricular valves, an early peaking or cutoff sign denotes a large regurgitant wave in the respective atrium and significant regurgitation. A rapid decay of the diastolic slope in semilunar valve regurgitation also can denote significant regurgitation but is exaggerated in cases of poor ventricular compliance and thus may not be specific. Pulmonic regurgitation (PR) may end prior to end diastole and may be related to poor ventricular compliance and/or severe regurgitation. Premature termination of diastolic flow is rarely seen in AR and usually denotes acute severe regurgitation.

a

Quantitative pulsed Doppler method

Doppler recording of VTI can be combined with 2D or 3D measurement of flow area to derive SVs at different sites. The difference between inflow and outflow SVs of the same ventricle is caused by the RVol in single valvular regurgitation. This method is simple in principle, however, accurate results require individual training (e.g., practice in normal patients where SVs at different sites are equal). Briefly, forward SV at any valve annulus—the least variable anatomic area of a valve apparatus—is derived as the product of CSA and the VTI, measured by pulsed Doppler at the annulus. Overall, assumption of a circular geometry has worked well clinically. In this case,

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