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 Table of Contents  
EXPERT DOCUMENT
Year : 2020  |  Volume : 4  |  Issue : 1  |  Page : 58-121

Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance


1 Houston Methodist Hospital, Houston, Texas, USA
2 Duke University Medical Center, Durham, North Carolina, USA
3 Northwestern University, Chicago, Illinois, USA
4 Mayo Clinic, Rochester, Minnesota, USA
5 University of California, San Francisco, California, USA
6 Baylor University Medical Center, Dallas, Texas, USA
7 Columbia University Medical Center, New York, USA
8 Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
9 Massachusetts General Hospital, Boston, Massachusetts, USA
10 University of Chicago, Chicago, Illinois, USA
11 Brigham and Women's Hospital, Boston, Massachusetts, USA
12 Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
13 MedStar Health Research Institute, Washington, DC, USA

Date of Web Publication11-Apr-2020

Correspondence Address:
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2543-1463.282191

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How to cite this article:
Zoghbi WA, Adams D, Bonow RO, Enriquez-Sarano M, Foster E, Grayburn PA, Hahn RT, Han Y, Hung J, Lang RM, Little SH, Shah DJ, Shernan S, Thavendiranathan P, Thomas JD, Weissman NJ. Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. J Indian Acad Echocardiogr Cardiovasc Imaging 2020;4:58-121

How to cite this URL:
Zoghbi WA, Adams D, Bonow RO, Enriquez-Sarano M, Foster E, Grayburn PA, Hahn RT, Han Y, Hung J, Lang RM, Little SH, Shah DJ, Shernan S, Thavendiranathan P, Thomas JD, Weissman NJ. Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2020 [cited 2020 Jun 7];4:58-121. Available from: http://www.jiaecho.org/text.asp?2020/4/1/58/282191

Yuchi Han, Dipan J. Shah and Paaladinesh Thavendiranathan are Society for Cardiovascular Magnetic Resonance Representative.







  Introduction Top


Valvular regurgitation continues to be an important cause of morbidity and mortality.[1] While a careful history and physical examination remain essential in the overall evaluation and management of patients with suspected valvular disease, diagnostic methods are often needed and are crucial to assess the etiology and severity of valvular regurgitation, the associated remodeling of cardiac chambers in response to the volume overload, and the characterization of longitudinal changes for optimal timing of intervention. In 2003, the American Society of Echocardiography along with other endorsing organizations provided, for the first time, recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional (2D) and Doppler echocardiography.[2] Advances in three-dimensional (3D) echocardiography and cardiovascular magnetic resonance (CMR) have occurred in the interim that provide additional tools to further delineate the pathophysiology and mechanisms of regurgitation and supplement current methods for assessing regurgitation severity.[3],[4],[5],[6] Furthermore, within this time frame, critical information linking Doppler echocardiographic measures of regurgitation severity to clinical outcome has been published.[7],[8],[9] This update on the evaluation of valvular regurgitation is a comprehensive review of the noninvasive assessment of valvular regurgitation with echocardiography and CMR in the adult. It provides recommendations for the assessment of the etiology and severity of valvular regurgitation based on the literature and a consensus of a panel of experts. This guideline is accompanied by a number of tutorials and illustrative case studies on evaluation of valvular regurgitation, posted on the following website (www.asecho.org/vrcases), which will build gradually over time. Issues regarding medical management and timing of surgical interventions are beyond the scope of this document and have been recently updated.[1]


  Evaluation of Valvular Regurgitation: General Considerations Top


Identifying the mechanism of regurgitation

Valvular regurgitation or insufficiency results from a variety of etiologies that prevent complete apposition of the valve leaflets or cusps. These are grossly divided into organic valve regurgitation (primary regurgitation) with structural alteration of the valvular apparatus and functional regurgitation (secondary regurgitation), whereby cardiac chamber remodeling affects a structurally normal valve, leading to insufficient coaptation. Etiologies of primary valve regurgitation are numerous and include degeneration, inflammation, infection, trauma, tissue disruption, iatrogenic, or congenital. Doppler techniques are very sensitive, and thus trivial or physiologic valve regurgitation, even in a structurally normal valve, can be detected and occurs frequently in right-sided valves.

It is not sufficient to only note the presence of regurgitation. One is obligated to describe the mechanism and possible etiologies, particularly in clinically significant regurgitation, as these affect the severity of regurgitation, cardiac remodeling, and management.[7],[10],[11] The mechanism of regurgitation is not necessarily synonymous with the cause. For example, endocarditis can cause either perforation or valvular prolapse. The resolution (spatial and temporal) of imaging modalities have markedly improved, resulting in identification of the underlying mechanism of regurgitation in the majority of cases. Transthoracic echocardiography (TTE) is usually the first-line imaging modality to investigate valvular regurgitation (etiology, severity, and impact). However, if the TTE is suboptimal, reliance on transesophageal echocardiography (TEE) or CMR would be the next step in evaluating the etiology or severity of regurgitation. Three-dimensional echocardiography has significantly enhanced our understanding of the mechanism of regurgitation and provides a real-time display of the valve in the 3D space. This is particularly evident when imaging the mitral, aortic, and tricuspid valves (TVs) with TEE.

Evaluating valvular regurgitation with echocardiography

General principles

TTE with Doppler provides the core of the evaluation of valvular regurgitation severity. Additional methods, echocardiographic (TEE) and nonechocardiographic (computed tomography, CMR, angiography), can be useful at the discretion of examining physicians based on the combination of the potential for these methods to be informative versus their potential risk. This could be particularly important for patients with suboptimal image quality and/or whenever there is a discrepancy between the clinical presentation/symptoms and the evaluation by echocardiography. When TTE provides a complete array of good quality data on the regurgitation, little or no additional information may be needed for the clinical care of patients. However, when the quality of the data is in question, or more precise/accurate measurements are required for clinical decision making, advanced imaging has an important role.

There are a number of principles to apply in the evaluation of valvular regurgitation with echocardiography:

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.

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.

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.

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.
Table 1: Echocardiographic parameters in the comprehensive evaluation of valvular regurgitation

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Echocardiographic imaging

The main goal of echocardiographic imaging is to define the etiology, mechanism, severity, and impact of the regurgitant lesion on remodeling of the cardiac chambers.

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.[12]

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.[13] 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.[14] 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).[15]

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.[14],[15]

Color Doppler imaging

Color flow Doppler is widely used for the detection of regurgitant valve lesions and is the primary method for assessment of regurgitation severity. This technique provides visualization of the origin of the regurgitant jet and its size (VC),[16] the spatial orientation of the regurgitant jet area in the receiving chamber, and, in cases of significant regurgitation, flow convergence into the regurgitant orifice [Figure 1]. Experience has shown that attention to these three components of the regurgitation lesion by color Doppler—as opposed to the traditional regurgitant jet area alone with its inherent limitations—significantly improves the overall accuracy of assessment of regurgitation severity. The following are important considerations for color Doppler imaging of regurgitant jets:
Figure 1: Depiction of the three components of a color flow regurgitant jet of mitral regurgitation: Flow convergence, vena contracta, and jet area

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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.[17] 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 Av2. (By extension, energy is given by Qv2 or Av3). The amount of momentum that is within a jet at its orifice remains constant throughout the jet.[18] 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,[17] but for clinical purposes, it suffices to know the following determinants of jet size [Table 2]:
Table 2: Factors that increase or reduce the color Doppler jet area

Click here to view


  • Jet momentum (Av2): 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.[19],[20] [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.[19],[20] 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.[21] 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.
Figure 2: 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 transesophageal echocardiography, will also depict a slightly larger jet

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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).[22] Thus, the cross-sectional area (CSA) of the VC represents a measure of the effective regurgitant orifice area (EROA),[23],[24] a true parameter of lesion severity.[25] The size of the hydraulic VC is independent of flow rate and driving pressure for a fixed orifice.[26] However, if the regurgitant orifice is dynamic, the VC may change during the cardiac cycle.[27] In general, the VC by color Doppler significantly overestimates the hydraulic VC and is dependent on flow rate, likely because of entrainment.[22] Despite these limitations, it remains a helpful semiquantitative measure of valve regurgitation severity.[22] 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[28] or pulmonary regurgitation (PR), less for MR,[16] and even less for TR.[29] 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.[30] 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.[31],[32],[33] 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.

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.[34] 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).

Pulsed Doppler

Pulsed Doppler is used combined with multiple measures of flow velocity as part of the quantitative assessment of valve regurgitation (see below). However, alterations in forward flow and reversed flow detected with pulsed Doppler associated with regurgitation can also be used as qualitative measures of valve regurgitation severity.

Forward flow

Valve regurgitation implies that the forward stroke volume (SV) across the affected valve during the cardiac cycle is increased.[35] 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.

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.[36],[37],[38],[39] 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.

Continuous wave Doppler

Recording of jet velocity with continuous wave Doppler (CWD) provides valuable information as to the velocity and gradient between the two cardiac chambers involved in the regurgitation, its time course, and timing of the regurgitation. The density of the signal is also helpful, provided the Doppler waveform is not overgained.

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.[40] 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.

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.[41]
Figure 3: M-mode color images depict timing of mitral regurgitation: classic holosystolic mitral regurgitation, late systolic mitral regurgitation due to mitral valve prolapse, and early systolic mitral regurgitation in a patient with cardiomyopathy and left bundle branch block. Single-frame measurements of effective regurgitant orifice area or vena contracta (width or area) will overestimate mitral regurgitation severity when it is not holosystolic

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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,[42],[43] 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.[44] 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.

Quantitative approaches to valvular regurgitation

There are few methods using echo Doppler techniques to quantitate valvular regurgitation. All these methods derive three measures of regurgitation severity:

  • The EROA, the fundamental measure of lesion severity
  • The RVol per beat, which provides a measure of the severity of the volume overload
  • The regurgitant fraction (RF) provides a ratio of the RVol to the forward SV specific to the patient.


Prior studies suggest that the absolute measurements of EROA and RVol provide the strongest predictors of outcome. It is uncertain whether normalization of these measures to body size (body surface area or body mass index) is superior to absolute values, particularly in women. Careful attention should be paid to assess whether the regurgitation covers its entire period (systole for atrioventricular, diastole for semilunar valves); for regurgitations limited to part of their flow period, the EROA should be normalized to the entire period of potential regurgitation or ignored, as it would overestimate the severity of regurgitation.[45] Overall, in such partial regurgitations, the RVol is a better measure of regurgitation severity.

There are three methods for quantitative assessment of valvular regurgitation:

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.[20],[46] 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.[46],[47] Overall, assumption of a circular geometry has worked well clinically. In this case,

SV = CSA × VTI = (πd2/ 4) × VTI =0.785× d2× VTI,

where d is the diameter of the annulus in centimeters, VTI in centimeters, and SV in milliliters.

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,
Figure 4: Echo-Doppler calculations of stroke volume at the left ventricular outflow tract and mitral valve annulus sites. In this example of severe mitral regurgitation, SVMV was 183 mL (d = 3.5 cm, velocity time integral =19 cm) and SVLVOT was 58 mL (d = 2.3 cm, velocity time integral =14 cm). This yielded an regurgitant volume of 125 mL and an regurgitant fraction of 125/183 or 68%. d: Diameter of the annulus, PW: Pulsed wave Doppler

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RVo1= SVRegValv− SVCompValv,

RF = RVol/SVRegValv,

where SVRegValv is the SV derived at the annulus of the regurgitant valve and SVCompValv is the SV at the competent valve.

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

EROA = RVol/VTIRegJet,

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.[46],[47] 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[48] 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.

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 (SVRegValv). If the forward SV (SVForward) 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.[25],[49] In such cases SVForward is measured on the nonregurgitant valve (aortic valve for MR or MV for AR). Hence calculations are the following:

SVLV= (end-diastolic LV volume) − (end-systolic LV volume),

RVo1= SVLV− SVForward,

EROA = RVol/VTIRegJet.

Methods for calculation of LV volumes by echocardiography have been previously detailed.[50] 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.[14],[51] 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.[3],[50]

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.[34] Color flow mapping offers the ability to image one of these hemispheres[52] 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 (2πr2) and the Va[52],[53],[54],[55],[56] as

RFlow =2πr2× Va,

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

EROA = (6.28× r2× Va)/PeakVRegJet,

where Peak VRegJet is the peak velocity of the regurgitant jet by CWD. The radius is expressed in centimeters and velocities in centimeters per se cond, allowing the EROA to be expressed in square centimeters. The RVol can be calculated as

RVol = EROA × VTIRegJet,

where VTIRegJet is the VTI of the regurgitant jet expressed in centimeters.

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:
Figure 5: Schematic representation of the flow convergence method (proximal isovelocity surface area). The example on the right shows the measurement of the proximal isovelocity surface area radius and the timing of the selection of the color frame for measurement (solid yellow arrow), corresponding to the maximal jet velocity by continuous wave Doppler (dashed arrow). Reg: Regurgitation, PKV: Peak velocity of regurgitant flow by continuous wave Doppler, VTI: Velocity time integral of the regurgitant jet by continuous wave Doppler

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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.[41] Previous studies using timed measurement in MR have shown that the regurgitation is often dynamic; two important precautions were highlighted[41],[53]: 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[57],[58] or overestimation in the case of late systolic primary MR.[59]
  • 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).[45] 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.
  • 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.[60] 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.[55] 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,[60] and if not, the method should not be reported.
  • 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.[61] Application of the standard PISA formula to such an elliptical orifice will lead predictably to flow underestimation.[62] 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.[63] 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.[63]


A few additional limitations of PISA should be noted.[64],[65] 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.[65],[66],[67] 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.[66],[67] 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.

Evaluating valvular regurgitation with cardiac magnetic resonance

While echocardiography remains the first line modality for assessment of valvular regurgitation, in some situations, it may be suboptimal. In these instances, CMR can play a useful role because of a number of unique advantages: it provides a view of the entire heart without limitations of imaging windows or body habitus, allows free choice of imaging planes as prescribed by the scan operator, is free of ionizing radiation, and does not require contrast administration. In addition to assessing the severity of the regurgitant lesion, a comprehensive CMR study is able to quantitate cardiac remodeling and provide insight into the mechanism of regurgitation.

Cardiac morphology, function, and valvular anatomy

The typical CMR study for evaluating valvular regurgitation involves the performance of a complete set of short-axis and long-axis (two-, three-, and four-chamber views) cine images using a steady-state free precession (SSFP) pulse sequence, which provides excellent signal-to-noise ratio and high blood-to-myocardium contrast.[68] The typical spatial resolution is 1.5-2.0 mm per pixel with 6- to 8-mm slice thickness and 2- to 4-mm interslice gap to produce a short-axis image every 10 mm from base to apex.[69] Some CMR laboratories have adopted a strategy of utilizing no interslice gap to theoretically improve the accuracy of SV quantification, especially for the RV with its unique geometry. Using this fast pulse sequence, temporal resolution of ≤45 msec (frame rates of 20-25/sec) can be achieved within a 5- to 8-second breath hold that is generally tolerable for most patients. In individuals who have significant difficulty with breath holding, a nonbreath-held ''real-time'' pulse sequence has been shown to provide comparable assessment of LV and RV volumes and ejection fraction with only a modest compromise in spatial and temporal resolution.[70]

An example of a typical series of cine images is shown in [Figure 6]. In addition to providing a comprehensive assessment of regional LV and RV function, this data set can be used to perform planimetry of LV and RV volumes at end diastole and end systole, thus determining ventricular SV and ejection fraction with the method of discs. While full details on performing planimetry of ventricular volumes can be found at the Society for Cardiovascular Magnetic Resonance position statement on standardized image interpretation and post processing,[6] there are a few key points worth mentioning:
Figure 6: Example cardiovascular magnetic resonance study for assessment of left ventricular function. Sequential short-axis slices are acquired from the mitral annular plane (base) to the apex of the left ventricular. Left ventricular end-diastolic volume is calculated by summation of the volume (area × thickness) of each short-axis slice during diastole. Left ventricular end-systolic volume is calculated by summation of the volume of each short-axis slice during systole. Note, this methodology requires no geometric assumptions

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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.[6]

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.[69] 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.[6] 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.[5]

Planimetry of LV epicardial contour

This can be performed to derive LV mass.

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.[71],[72]

It is important to note that normal reference ranges for left and right cardiac chamber volumes by CMR are higher than for echocardiography[71],[72] and that correlation between the two modalities is improved with use of 3D echocardiography and/or administration of echocardiographic contrast.[14],[15],[73],[74] The ability to image in any plane makes CMR robust for assessment of valvular anatomy[75] 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.

Assessing severity of regurgitation with CMR

Assessing the severity of valvular regurgitation can be performed via a variety of methods: (1) visual assessment of the extent of signal loss due to spin dephasing on cine CMR acquisitions,[76],[77] (2) planimetry of the ARO area from the cine CMR acquisitions of the valve,[78],[79] or (3) quantitation of the RVol. While the first two methods can be used to obtain a qualitative assessment of regurgitant severity, the last method is the most robust and the crux of CMR assessment of valvular regurgitation. The following are approaches and considerations for quantitation of valvular regurgitation [Table 3]:
Table 3: Cardiovascular magnetic resonance methods for valvular regurgitation

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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.[80],[81],[82],[83]
Figure 7: Cardiovascular magnetic resonance 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 aortic regurgitation, the reverse flow represents the directly measured volume of aortic regurgitation. The right side of the figure demonstrates the same, performed at the pulmonary artery trunk to derive pulmonary artery flow

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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.
Figure 8: Example cardiovascular magnetic resonance method for quantification of mitral regurgitation. The volume of the left ventricular 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 left ventricular, left ventricular stroke volume, is computed as the difference between left ventricular end-diastolic volume and left ventricular end-systolic volume. In this example LV SV is 150 mL. The volume of blood crossing the aortic (aortic regurgitation) 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 regurgitant volume is computed as the difference between the left ventricular stroke volume and aortic forward stroke volume; in this example, 70 mL

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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.[69] 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.[84]

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.[85] One study in MR and another in AR have focused on RVol/fraction thresholds for prognosis.[86],[87] 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[2] and the recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines[1] are used.

Strengths and limitations of CMR

CMR has a number of unique strengths, which make it ideal for assessment of valvular disease [Table 4]. Specifically, the free choice of imaging planes allows for a comprehensive assessment of all four cardiac valves without limitations of acoustic windows. In addition, volumetric assessment by CMR has been shown to have high interstudy reproducibility and therefore may be ideal for serial assessment.
Table 4: Strengths and limitations of cardiovascular magnetic resonance in evaluation of valvular regurgitation

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The limitations of CMR are listed in [Table 4] and include its inability to be performed in patients with certain implanted devices.[88] A comprehensive review of all contraindicated devices is beyond the scope of this document, but it is essential that all CMR laboratories perform careful screening on all patients referred for imaging. Since most CMR acquisitions are performed in a segmented fashion (obtained over multiple cardiac cycles), arrhythmias such as atrial fibrillation or premature ventricular contractions may pose a challenge for standard breath-held phase-contrast CMR sequences. CMR is also not as readily available as echocardiography, cannot be performed at the bedside or in some patients with claustrophobia, and is generally a more expensive modality. There are no uniform thresholds for grading severity of regurgitation, and there is a paucity of outcome data available regarding specific thresholds. Lastly, CMR is unable to assess pressures inside a vessel or cardiac chamber.



When is CMR indicated?

While echocardiography remains the first-line modality for assessment of valvular regurgitation, CMR is generally indicated when (1) echocardiographic images are suboptimal, (2) when there is discordance between 2D echocardiographic features and Doppler findings (e.g., ventricular enlargement greater than expected on the basis of Doppler measures of valvular regurgitation), or (3) when there is discordance between clinical assessment and severity of valvular regurgitation by echocardiography.[1] Specific scenarios when CMR may be indicated will be described in further detail in subsequent sections for individual valvular lesions.

The direct method described above for quantification of aortic or PR and the indirect method described for mitral and TR are independent of other coexisting valvular lesions, and therefore CMR may be especially useful in the setting of multiple valvular lesions when echocardiographic assessment is challenged. This will be presented in more detail in the section on multivalvular disease.

Grading the severity of valvular regurgitation

Characterization of the severity of regurgitant lesions is among the most difficult problems in valvular heart disease. Such a determination is important since mild regurgitation does not lead to remodeling of cardiac chambers and has a benign clinical course, whereas severe regurgitation is associated with significant remodeling, morbidity and mortality.[1] Contributing to the difficulty of assessment of regurgitation is the lack of a true gold standard and the dependence of regurgitation severity on the hemodynamic conditions at the time of evaluation. Although angiography has been used historically to define the degree of regurgitation based on opacification of the receiving chamber, it is also dependent on several technical factors and hemodynamics.[11],[89],[90] For example, an increase in blood pressure will increase all parameters of aortic or MR, be it assessed as RF or angiographic grade. Furthermore, the angiographic severity grades, which have ranged between three and five grades, have only modest correlations with quantitative indices of regurgitation.[11],[46],[90]

Doppler and CMR methods for valvular regurgitation have been validated in animal models against independent flow parameters, and clinically, against the angiographic standard and each other. The majority of these studies have involved left-sided cardiac valves. For Doppler echocardiography, and as discussed above, there are several qualitative and quantitative parameters that can provide assessment of valvular regurgitation. Although this adds to the complexity of evaluation, the availability of these different parameters provides an internal check and corroboration of the severity of the lesion, particularly when technical or physiologic conditions preclude the use of one or the other of these indexes. For CMR, the evaluation involves fewer parameters, is mostly quantitative, but is still influenced by technical and physiologic factors. In order to mitigate the effect of these factors within each individual exam, quantitative internal checks within the CMR exam should be employed. For example, in patients with isolated MR, the difference between the LV SV and aortic total forward flow should be the same as the difference between the LV SV and the pulmonary artery (PA) total forward flow or RV SV. Thus, an integrative, comprehensive approach is essential. In echocardiography, if there are signs suggesting that the regurgitation is significant and the quality of the data lends itself to quantitation, it is desirable for echocardiographers with experience in quantitative methods to determine quantitatively the degree of regurgitation, particularly for left-sided lesions. Ultimately, the interpreter of either echocardiography or CMR must integrate the information and disregard ''outlying'' data (because of poor quality or a physiologic condition that alters accuracy of a certain parameter), making a best estimate of regurgitation severity. The consensus of the writing group is to classify grading of severity of regurgitation into mild, moderate, and severe. ''Trace'' regurgitation is used in the event that regurgitation is barely detected. Usually this is physiologic, particularly in right heart valves and MV, and may not produce an audible murmur. Since the severity of regurgitation may be influenced by hemodynamic conditions, it is essential to record the patient's blood pressure, heart rate, and rhythm at the time of the study and note the patient's medications whenever possible. When following a patient with serial examinations, these factors need to be considered in comparing the severity of regurgitation and its hemodynamic consequences and actual studies reviewed and compared because of inherent variability of techniques and measurements.


  Mitral Regurgitation Top


Anatomy of the mitral valve and general imaging considerations

The MV apparatus includes the anterior and posterior mitral leaflets, the mitral annulus, chordae tendinae, papillary muscles, and the underlying LV myocardium. Echocardiographic views and their relation to mitral anatomy and the three scallops of each leaflet have been reviewed in detail.[91],[92] Typically, a 2D long-axis view runs through the middle portion of the anterior leaflet (A2) and the middle scallop of the posterior leaflet (P2). A short-axis view is useful in defining the exact location of pathology because it allows imaging of both leaflets and the commissures. The four-chamber view can cut through the leaflets at different locations. A cross-commissural view (typically by TEE but approximated by the transthoracic apical two-chamber view) is good at identifying the lateral (P1) and medial (P3) scallops of the posterior leaflet and the middle (A2) anterior leaflet. The optimal view of the coaptation line is a 3D en face view by either TTE or TEE. Three-dimensional echocardiography can provide detailed views of the complex structure of the MV apparatus, either from the LA or the LV.[3] This facilitates both anatomic and functional interpretation, allowing precise localization of abnormal MV anatomy, particularly with TEE [Figure 9].[3],[4],[12],[93]
Figure 9: Three-dimensional echocardiographic frames of mitral valves from the left atrium view depicting a normal valve with delineation of the anterior and posterior scallops, a patient with fibroelastic deficiency and a flail P2 segment, as well as a patient with Barlow's disease

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Identifying the mechanism of MR: Primary and secondary MR

The mechanism of MR can be divided broadly into two categories, based on whether the mitral leaflets exhibit significant pathological abnormality or not [Table 5]. In primary MR, an intrinsic abnormality of the leaflets causes the MR, whereas secondary MR results from distortion of the MV apparatus due to LV and/or LA remodeling. Hence, most secondary MR is a disease of the LV. It is important to distinguish primary from secondary MR as therapeutic approaches and outcomes differ. It is also useful to consider whether leaflet motion is intrinsically normal or abnormal according to the Carpentier classification[94] [Figure 10]. Type I leaflet motion is normal but can be associated with MR if there is annular dilation (secondary MR) or a leaflet perforation. Type II leaflet motion is excessive and is most commonly due to MVP or flail leaflet. Type III leaflet motion is restrictive, commonly seen in the presence of LV dilation (secondary MR) or rheumatic MV disease or other postinflammatory conditions such as collagen vascular disease, radiation injury, carcinoid syndrome, or drug-induced inflammatory changes. [Table 6] compares the MV apparatus, cardiac remodeling, and jet characteristics in primary and secondary MR.
Table 5: Etiology of primary and secondary mitral regurgitation

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Figure 10: Depiction of mechanisms of mitral regurgitation as per the Carpentier classification

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Table 6: Mitral valve apparatus, cardiac remodeling, and jet characteristics in primary and secondary mitral regurgitation

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Primary MRT

The most common cause of primary MR is myxomatous degeneration, most frequently MVP.[94] MVP is a spectrum of disease ranging from a focal abnormality of a mitral leaflet to diffuse involvement of both leaflets. Fibroelastic deficiency refers to focal segmental pathology with thin leaflets, while Barlow's disease refers to diffuse thickening and redundancy, typically affecting multiple segments of both leaflets and chordae [Figure 9]. Characteristically, the MR occurs during mid-late systole when the laxity resulting in leaflet malcoaptation is greatest. In such cases, failure to recognize that MR is not holosystolic can lead to overestimation of MR severity by methods that rely on single-frame color Doppler measurements acquired when MR is at its maximum [Figure 11].[45]
Figure 11: Late systolic mitral regurgitation in mitral valve prolapse. (a) Midsystolic frame shows no mitral regurgitation by color Doppler. Left atrium volume index was normal (26 mL/m2). (b) Late-systolic frame shows an eccentric mitral regurgitation jet with a large flow convergence. (c) Continuous wave Doppler profile of mitral regurgitation jet demonstrates that mitral regurgitation is confined to late systole (onset at yellow arrow, small velocity time integral of jet, dotted contour). (d) Pulsed wave Doppler of mitral inflow shows an E wave velocity of 75 cm/sec with normal E/e′ ratio consistent with normal left atrium pressure. Calculation of effective regurgitant orifice area will overestimate regurgitation severity: EROA =2πr2× Va/PkVreg=2 × 3.14× 12× 29.9/527 = 0.36 cm2. Quantitation of regurgitation should rely on regurgitant volume by either proximal isovelocity surface area or volumetric measures. RVol by PISA = EROA × VTIreg=0.36× 76 = 27 mL

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Using echocardiography, MVP is diagnosed ideally in the parasternal long-axis window as systolic displacement of the mitral leaflet into the LA of at least 2 mm from the mitral annular plane.[95] If parasternal windows are of poor quality, the apical long-axis view can also be used, although the latter is less standardized and thus more variable. Diagnosis of MVP should be avoided in the apical four- or two-chamber windows as these windows image the MV annulus along the low points of the saddle-shaped MV annulus, falsely making the leaflets appear to be displaced into the LA from the annular plane.[96]

A flail leaflet is part of the MVP spectrum and occurs when the leaflet edge, not just the leaflet body, is located in the LA with free motion. It occurs most commonly from rupture of the marginal chords. A flail leaflet almost always denotes severe MR and is clearly associated with adverse outcomes.[97],[98],[99],[100] An extreme of flail MV is papillary muscle rupture. Other etiologies of primary MR are listed in [Table 5].

Secondary MR

The leaflets are intrinsically normal in secondary MR, although minor leaflet thickening and annular calcification can be present. With adverse LV remodeling, one or both of the mitral leaflets are pulled apically into the LV as a result of the outward displacement of the papillary muscles. This results in incomplete mitral leaflet closure.[101],[102],[103],[104],[105],[106],[107] The leaflets are apically displaced, tethered, and may have restricted mobility, especially the posterior leaflet. Leaflet tethering is often asymmetric, particularly in ischemic as opposed to dilated cardiomyopathies, where the P3 scallop is tethered more apically than is P1.[106] In such cases, the regurgitant orifice tends to be largest at the posteromedial scallop (P3), it may be irregularly shaped, and there may be two separate MR jets, which sometimes cross each other in the LA [Figure 12] and [Figure 13]. Additional echocardiographic features of tethering include a bend in the body of the anterior leaflet from tethering of the basal or strut chordae (“seagull” or “hockey stick'' sign), with a posteriorly directed jet. This should not be confused with MVP.
Figure 12: (a) An example of significant secondary mitral regurgitation in a dilated cardiomyopathy with marked tenting (arrows) of the mitral valve. (b) Parasternal short-axis color Doppler showing regurgitation along the entire length of the valve coaptation. (c) Pulsed wave Doppler at tips of the mitral valve leaflets with high E velocity. (d) Triangular shape to the continuous wave spectral in the setting of significant mitral regurgitation. (e and f) Proximal isovelocity surface area from apical three- and two- (commissural) chamber views showing the different shapes of the flow convergence (nonhemispheric) and vena contracta (noncircular). Assumption of a hemispheric flow convergence or circular vena contracta would underestimate mitral regurgitation

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Figure 13: Short-axis views of mitral regurgitation in four different patients. (a) Relatively round orifice in myxomatous mitral valve with flail P2 scallop. (b) Patient with secondary mitral regurgitation and two separate mitral regurgitation jets (arrows). (c) Noncircular mitral regurgitation located at P3 and P2 scallops in a patient with ischemic cardiomyopathy and a large inferoposterior wall motion abnormality. (d) Elliptical mitral regurgitation jet extending from commissure to commissure in a patient with ischemic cardiomyopathy

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Several methods have been proposed to quantify the degree of tethering. The most common is a simple area measurement from the leaflet tips to the annular plane (tenting area) performed at mid-systole where the area is at a minimum. Another measure is coaptation height or depth, which measures the maximal distance from the leaflet tips to the annular plane and appears to correlate with the presence and severity of ischemic MR. More recently, 3D echocardiography has been applied to quantify leaflet tethering by measuring the tethering distance from papillary muscle tip to the mitral annulus and measuring the tenting volume (volume from leaflets to annular plane). While there is a general correlation between tenting area or height and severity of secondary MR, these measurements are not precise in discriminating mild, moderate, or severe MR,[108] particularly since the leaflets may vary in size and thus accommodate the outward tethering. Mitral annular dilation also plays a role in the development of functional MR by increasing the area needed for the mitral leaflets to cover.[108],[109],[110] However, annular dilation alone without leaflet tethering is an uncommon cause of significant secondary MR, such as in patients with severe LA dilatation from long-standing atrial fibrillation.[111],[112]

Mixed etiology

Occasionally, patients may present with mixed etiologies of MR that include both primary and secondary MR. For example, a patient with long-standing ischemic or nonischemic cardiomyopathy and secondary MR may rupture a chord and develop a flail leaflet. Conversely, a patient with mild or moderate MR from primary leaflet pathology may have a myocardial infarction and develop worse MR from tethering of the already abnormal leaflets. Although most cases of MR fall into the primary or secondary classification scheme, it should be recognized that mixed etiology can and does occur. It is important to emphasize that a severely restricted posterior leaflet due to ischemic wall motion abnormality may result in anterior leaflet override. In such cases, the anterior leaflet is not prolapsed and this does not represent a mixed etiology.

Hemodynamic considerations in assessing MR severity

Acute MR

Acute MR is far less common than chronic MR and usually results in hemodynamic compromise. It occurs most commonly due to ruptured papillary muscle after acute myocardial infarction, ruptured chordae tendinae resulting in a flail leaflet, or leaflet destruction due to endocarditis and less frequently due to rapid onset of cardiomyopathy (e. g., Takotsubo, myocarditis, or postpartum cardiomyopathy). Patients often present with pulmonary edema from elevated LA pressure, tachycardia, and severe hypotension from loss of forward SV. The combination of hypotension and high LA pressure results in a low driving pressure and therefore lower MR jet velocity across the MV. Accordingly, color Doppler imaging often will not show a large turbulent flow disturbance, and thus MR may be underestimated or not appreciated at all. The color Doppler jet is usually markedly eccentric, which again can underestimate MR severity. Anatomic imaging of flail leaflet or ruptured papillary muscle and the finding of a hyperdynamic LV with low Doppler systemic output along with clinical findings should be enough to substantiate the diagnosis, even if color Doppler does not show a large MR jet.[113] Systolic flow reversal in the pulmonary veins is usually present and is helpful. TEE may be better at identifying acute severe MR. The Doppler methods for assessing MR severity in the remainder of this section apply to chronic and not to acute severe MR.

Dynamic nature of MR

Temporal variation of MR during systole

The regurgitant orifice area in MR is often a variable quantity during the cardiac cycle, whether holosystolic or not. The measured EROA as described earlier differs from the dynamic regurgitant orifice area in that it is usually derived from static, maximal values from single systolic frames. Although MR is classically holosystolic, patients with MVP often have no MR in early systole, with a relatively large EROA limited to mid- or late systole.[45] Compared with patients with holosystolic MR, those with late systolic MR yield lower RVols, despite similar EROA and jet areas.[45] In such patients, RVol has been shown to be superior to EROA in predicting cardiac death, admission for congestive heart failure, or new-onset atrial fibrillation.[45] On the other hand, patients with secondary MR often exhibit a biphasic pattern of MR, with an initial EROA peak in early systole, a decline in midsystole, and a second peak in late systole and isovolumic relaxation.[41],[57],[58] Occasionally, transient MR limited to early systole is seen, particularly with bundle branch block. Thus, duration and timing of MR should be carefully evaluated. EROA to grade MR severity [Figure 3] should be used only if adjusted for the duration of MR, where feasible. Volumetric methods for assessing MR would forgo the above limitations and are preferred in nonholosystolic MR.

Effect of loading conditions

Grading of MR severity can be significantly impacted by hemodynamic changes, particularly blood pressure.[114] [Figure 14] shows an example of the dynamic nature of MR. Hemodynamic variation could be seen with conscious sedation (during TEE) but is particularly challenging in the operating room, brought about by anesthesia and vasoactive agents. In general, the commonly encountered intraoperative decrease in loading conditions or contractility is more likely to result in an underestimation of the MR grade compared with ambulatory conditions.[115]
Figure 14: Importance of mitral regurgitation jet velocity in mitral regurgitation. The images are from two patients with functional ischemic mitral regurgitation due to posterior leaflet restriction, left ventricular ejection fraction 30%, and similar appearance of eccentric mitral regurgitation jets directed laterally. The patient in the top panels has a low mitral regurgitation velocity (4.1 m/sec) consistent with low blood pressure and/or elevated left atrium pressure. His blood pressure was 105/76 mmHg. Effective regurgitant orifice area by proximal isovelocity surface area is 0.3 cm2 with an regurgitant volume of 42 mL. The patient in the lower panels has a similar mitral regurgitation jet appearance but has a peak mitral regurgitation velocity of 6.4 m/sec due to hypertension (178/94 mmHg). Effective regurgitant orifice area is 0.08 cm2 with an regurgitant volume of 17 mL. Despite similar mitral regurgitation jet appearance on color Doppler, the patient in the top panel has moderate mitral regurgitation; the patient in the bottom panel has mild mitral regurgitation

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Consequently, the preoperative MR grade may be preferred to guide therapeutic decisions. Intraoperative optimization of loading conditions may be used to guide surgical decision making.[116],[117] Patients with secondary MR may demonstrate significant variation in severity from one occasion to the next, depending on volume status and other hemodynamic variables.

Systolic anterior MV motion

Dynamic changes in MR severity can also occur with systolic anterior motion of the MV and LVOT obstruction, most commonly associated with either hypertrophic obstructive cardiomyopathy or following valve repair with a ring annuloplasty. This phenomenon has also been described in some patients with LV dysfunction and a hyperdynamic base following acute myocardial infarction or Takotsubo cardiomyopathy. Anterior MV leaflet motion exceeds that of the posterior leaflet, thereby creating malcoaptation with a posteriorly directed jet.[118],[119],[120]

Pacing and dysrhythmias

The severity of MR can also be influenced by cardiac dysrhythmias and pacing.[121] RV pacing has been associated with development of functional MR,[122] and cardiac resynchronization therapy has been shown to improve functional MR; the response, however, is not uniform.[123],[124],[125],[126] Atrial fibrillation is commonly experienced by patients with MR and may confound its grading due to rapid ventricular response or variable cycle lengths. In patients with a prolonged PR interval due to atrioventricular conduction abnormalities, atrial systole can induce premature ineffective valve closure, accompanied by varying degrees of diastolic MR.[127] Careful attention to heart rhythm and pacing is therefore important in evaluating MR.

Doppler methods of evaluating MR severity

There are several methods for evaluating the severity of MR with Doppler echocardiography. The various methods, their optimization, advantages, and limitations are hereby discussed and highlighted in [Table 7].
Table 7: Doppler echocardiography in evaluating severity of mitral regurgitation

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Color flow Doppler

Color Doppler flow mapping is the primary modality to screen for MR [Figure 15]. There are three methods of evaluating MR severity by color flow Doppler: regurgitant jet area, VC, and flow convergence. Although jet area was the first method used for assessing MR severity, its sole use is less accurate than the latter two methods.
Figure 15: Color Doppler panel of mild and severe mitral regurgitation (central and eccentric). In the eccentric, wall-impinging jet case, the jet area is small, but the flow convergence and vena contracta are large and alert to the severity of regurgitation

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Regurgitant jet area

Although jet area is excellent for excluding MR, it is not reliable for grading MR severity, even when indexed for LA area.[2],[128] Patients with acute severe MR, in whom blood pressure is low and LA pressure is elevated, may have a small color flow jet area, whereas hypertensive patients with mild MR may have a large jet area. Jet area is also dependent on the mechanism of MR. With flail leaflet, the MR jet is often very eccentric; jet area is small, underestimating MR severity as the jet spreads out along the wall and loses energy.[19] In secondary MR, central jets with a slit-like orifice can appear large, particularly in the two-chamber view, along the line of MV coaptation, even when the EROA is small. Therefore, MR grade should not be determined by “eyeballing” the color flow area of the MR jet alone, without considering the origin of the jet (VC) and its flow convergence. However, a small noneccentric jet with a narrow VC (<0.3 cm) and no visible flow convergence region usually indicates mild MR [Table 7]. Conversely, a large jet with a wide VC (≥0.7 cm) and where the jet wraps around the LA and penetrates into the pulmonary veins is almost always severe MR. Anything else should alert the observer to use the methods below.

Vena contracta (width and area)

The VC is a measure of the effective regurgitant orifice.[26] For MR, the VC width (VCW) should be imaged preferably in a parasternal long-axis view (axial resolution) and measured using zoom mode at the narrowest portion of the jet as it emerges from the orifice [Figure 1]. A VC <0.3 cm usually denotes mild MR; ≥ 0.7 cm is specific for severe MR.[2],[128] Intermediate values overlap substantially between MR grades, so additional methods should be used for confirmation. VCW works equally well for central and eccentric jets,[24] however, it is dependent on orifice geometry, underestimating MR severity if there are multiple jets or if there is a markedly elliptical (noncircular) orifice shape, as often seen in secondary MR.

The development of 3D echocardiography has allowed direct measurement of VC area (VCA). Multiplanar reconstruction tools are used to orient orthogonal imaging planes (x and y) through the long axis of the MR jet, and the z plane is adjusted perpendicularly through the narrowest CSA of the VC [Figure 16]. VCA can then be measured by manual planimetry of the color Doppler signal. If there are multiple jets, the imaging plane should be oriented through each jet separately for tracing. Care should be taken to only measure the highest velocity, aliased signal so as not to include low-velocity (dark color) eddies that are not part of the jet core. Limitations include technically difficult images, dynamic variation in the regurgitant orifice over the cardiac cycle, and the color Doppler blooming effect, in which the color Doppler signal is larger than the jet core itself.[129]
Figure 16: Two cases showing evaluation and quantitation of vena contracta area with three-dimensional echocardiography and multiplanar reconstruction. A case of primary mitral regurgitation (upper panels) with a circular vena contracta area and hemispheric proximal isovelocity surface area and another with secondary mitral regurgitation (lower panels) with elliptical vena contracta area and nonhemispheric proximal isovelocity surface area

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Three-dimensional echocardiography has shown that the regurgitant orifice is often crescent shaped in secondary MR [Figure 16].[30],[31],[32],[33],[61],[62],[130],[131],[132],[133] In such cases, the assumption of circular orifice geometry inherent to VCW may result in underestimation of secondary MR. In a recent study, 3D VCA >0.4 cm2 denoted severe MR.[30] However, studies relating 3D VCA to outcomes have not been performed yet.

Flow convergence (PISA)

In MR, PISA is more accurate for central regurgitant jets than eccentric jets and for circular orifices than noncircular orifices. It is usually easy to identify the aliasing line of the hemisphere; however, it can be difficult to judge the exact location of the orifice. Optimization of acquisition and measurement of PISA are essential and have been discussed earlier, as any error in radius is subsequently squared in the derivation of EROA. Errors of 10%-25% are common even among expert readers[134] and are the smallest for central jets; therefore, PISA should always be considered in the context of the other echo/Doppler findings. The dynamic nature of the orifice in MR can also lead to errors with the PISA formula. The regurgitant orifice is often crescent shaped in secondary MR. In such cases, the assumption of circular orifice geometry inherent to 2D PISA may result in underestimation of secondary MR. This may partly explain the finding that lower values of EROA by 2D PISA are associated with worsened prognosis in secondary MR.[135],[136],[137] Also, it should be remembered that PISA EROA, like VCW or VCA, is calculated from a single-frame image. These parameters therefore will overestimate MR severity when MR is not holosystolic [Figure 11]. Finally, poor alignment of the CWD beam with an eccentric jet will lead to an underestimation of velocity and an overestimation of the EROA.

A simplified approach to PISA quantitation has been validated.[138] Assuming a 5 m/sec MR jet (100 mmHg pressure difference between LV and LA in systole), baseline shifting the color Doppler display to a Va of around 40 cm/sec and measuring the aliasing radius r yields a simplified estimate of EROA = r2/ 2. This simplification does not hold at extremes of blood pressure, but the vast majority of patients have jets between 4 and 6 m/sec for which this approximation is reasonable. Generally, in primary MR, an EROA ≥ 0.4 cm2 is consistent with severe MR, 0.20-0.39 cm2 with moderate, and <0.20 cm2 with mild MR.

Continuous wave Doppler

In most patients, maximum MR velocity is 4-6 m/sec due to the high systolic pressure gradient between the LV and LA. The velocity itself does not provide useful information about the volumetric severity of MR, but it does provide clues to the hemodynamic consequences of MR. A low MR peak velocity (e.g., 4 m/sec) suggests hemodynamic compromise (low blood pressure/elevated LA pressure). In addition to peak velocity, the contour of the velocity profile and its density are useful. A truncated, triangular jet contour with early peaking of the maximal velocity indicates elevated LA pressure or a prominent regurgitant pressure wave [Figure 12]. The density of the CWD signal is a qualitative index of MR severity; a dense signal suggests significant MR, whereas a faint signal is likely to be mild or trace MR. CWD should also be used to interrogate the TR jet to estimate PA systolic pressure, another indirect clue as to MR severity and compensation for the volume overload.

Pulsed Doppler

Pulsed Doppler methods can be used to calculate SVs at the LVOT and MV level and determine RVol and RF [Figure 4] and [Table 7].[20],[46],[139],[140] RVol can also be calculated by comparing Doppler LVOT SV to total LV SV derived from LV volumes. Because 2D echocardiography tends to underestimate LV volumes, 3D LV volumes are preferable, and ultrasound contrast should be used if needed to identify endocardial borders.[3],[50]

Pulsed Doppler tracings at the mitral leaflet tips are commonly used to evaluate LV diastolic function but can be helpful in MR. Patients with severe MR have a dominant early filling (increased E velocity) due to increased diastolic flow across the MV (E velocity is usually ≥1.2 m/sec). An impaired relaxation pattern with a low E velocity and A wave dominance virtually excludes severe MR. Because of the effect of relaxation on mitral inflow indices, these observations are more applicable in individuals older than 50 years of age or in conditions of impaired myocardial relaxation.[128] The mitral inflow pattern is also more reliable for assessing primary MR because, in secondary MR, it is difficult to determine whether E dominance is due to significant MR or elevated LV filling pressures. The peak E velocity is also affected by even mild degrees of mitral stenosis in the presence of rheumatic disease, mitral annular calcification, or a mitral annular ring.

Pulmonary vein flow

Pulsed Doppler of pulmonary venous flow is a useful adjunct to evaluating the hemodynamic consequences of MR. With increasing severity of MR, there is a diminution of the systolic velocity, culminating with systolic flow reversal in severe MR. Since the MR jet may selectively enter a vein, sampling more than one vein is recommended, especially during TEE. One limitation of the pulmonary venous pattern is that elevation in LA pressure of any etiology as well as atrial fibrillation may also result in a blunted systolic forward flow.[141]

Thus, systolic blunting is less valuable in secondary MR than in primary MR. As a result, the pulmonary venous flow pattern should be used adjunctively with other parameters. Nevertheless, the finding of systolic flow reversal in more than one pulmonary vein is specific for severe MR. If the MR is confined to late systole, flow reversal may be present only during late systole. It is also important to distinguish true systolic flow reversal from contamination by the MR jet itself, a more difficult task during TTE compared with during TEE.

Assessment of LV and LA volumes

Primary significant MR imposes a pure volume overload on the LV. If chronic, such a condition would result in chamber dilation and ultimate LV dysfunction if untreated.[1] It is important to consider body size in evaluating LV size, particularly in patients with small body surface area such as women.[13] On the other hand, in secondary MR, the relation between LV dilation and MR severity is complicated because MR results from LV dysfunction but also may contribute to it. In either case, it is important to measure both LV chamber size and function for determining the need for surgical or percutaneous intervention and for measuring any reverse LV remodeling after therapy.[142] Three-dimensional echocardiography is now recommended for evaluation of LV volumes because it offers improved accuracy and precision compared to 2D echocardiography.[3],[50] Echocardiographic measurements of global longitudinal strain may become useful in evaluating earlier myocardial dysfunction in MR[143],[144] that could be masked by volume-based measurements, such as LV ejection fraction (LVEF).

LA dilation is also an expected consequence of severe MR. A normal LA size generally excludes severe chronic MR. LA volumes are superior to LA diameters in evaluating LA dilation and in predicting outcomes and atrial fibrillation.[145] However, LA dilatation can occur in many disease states including hypertension and atrial fibrillation. Therefore, a dilated LA does not necessarily imply severe MR.

Role of exercise testing

Exercise echocardiography can be useful in evaluating patients with both primary MR and ischemic functional MR.[128] Exercise may unmask the presence of symptoms and establish functional capacity in patients who are sedentary or have equivocal symptoms. Failure of LVEF to increase normally with exercise predicts worse postoperative LV function in primary MR.[146] Color Doppler inclusive of changes in EROA derived with PISA during exercise can be technically difficult to capture due to tachypnea and tachycardia and may be best performed during supine bicycle exercise. Increases in EROA (≥13 mm2) during exercise have been shown to be associated with symptoms and adverse outcome in secondary MR.[136] Lastly, increased PA pressure during exercise (≥60 mmHg) may be important in asymptomatic severe primary MR.[1],[136],[146],[147] There is currently no role for pharmacologic stress echocardiography to evaluate severity of MR or direct its management.

Role of TEE in assessing mechanism and severity of MR

TEE is indicated to evaluate MR severity in patients in whom TTE is inconclusive or technically difficult. In addition, TEE is particularly well suited to identify the underlying mechanism of MR and for planning MV surgery or percutaneous valve procedures and provides overall a better accuracy in localizing MV pathology.[12] The majority of the above methods of quantifying MR can be used during TEE. In particular, the higher resolution of TEE, multiplane and 3D capabilities, and proximity to the MV makes VC imaging and PISA easier and probably more accurate. Furthermore, interrogation of all pulmonary veins is generally feasible and better than with TTE. A few cautionary points are worth mentioning regarding TEE. Since jet size is affected by transducer frequency, PRF, and signal strength, the same jet may appear larger on TEE compared with on TTE. Because sedatives are used, careful attention to blood pressure is important; secondary MR may appear less severe if the blood pressure is significantly lowered. Quantitative pulsed Doppler is more challenging and is the most affected quantitative MR parameter with TEE: acquisition of pulsed Doppler in the LVOT is usually hampered by angulation issues, leading to underestimation of systemic output.

Role of CMR in the assessment of MR

CMR offers several important advantages in the assessment of MR. This includes identifying the mechanism of MR, quantifying MR severity, and determining its consequences on cardiac remodeling.

Mechanism of MR

Like echocardiography, CMR can provide information about the mechanism of MR by identifying morphologic abnormalities of the MV apparatus.[148] The presence of billowing, prolapse, or flail segments can be identified by dedicated cine imaging performed through the different scallops of the MV leaflets [Figure 17].[149],[150] In secondary MR, CMR offers accurate assessment of LV dilation and function in addition to identification of myocardial and papillary muscle scar [Figure 17].[151],[152]
Figure 17: Examples of primary and secondary mitral regurgitation evaluated with cardiovascular magnetic resonance. There is flail of the posterior mitral valve leaflet (red arrow) with highly eccentric anteriorly directed jet of mitral regurgitation. Volumetric calculations showed an left ventricle end-diastolic volume of 235 mL, end-systolic volume of 75 mL, and thus a total left ventricle stroke volume of 160 mL. The systemic aortic stroke volume was 94 mL. Thus, the mitral regurgitant volume was 66 mL and the regurgitant fraction was 66/160 or 41%. In the case of secondary mitral regurgitation, the mitral leaflets are seen tethered apically with the jet of mitral regurgitation (red arrow). The total left ventricle stroke volume was 77 mL with an regurgitant volume of 32 mL and an regurgitant fraction of 42%. Late gadolinium enhancement showed localization of a previous infarction in the posterior wall. This is consistent with moderate mitral regurgitation

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Methods of MR quantitation

MR can be assessed using several techniques by CMR. This includes qualitative or semiquantitative visual assessment of MR jet based on spin dephasing in the LA,[153] measurement of the VCA or anatomical regurgitant orifice area on short-axis cine of phase-contrast images,[77],[154] and quantification of RVol and RF.[155],[156],[157] Among these techniques, quantification of RVol and fraction is recommended [Figure 8] and [Figure 17]. The suggested preference order for calculation of RVols is the use of

  • The difference between LV SV using planimetry of short-axis cine images and aortic SV obtained by phase-contrast images
  • The difference in LV and RV SV by endocardial contouring of LV and RV cine images
  • The difference between the mitral inflow SV and aortic SV by phase-contrast imaging


The RF can be calculated by dividing the RVol by the LV SV for the first two methods and by the mitral inflow SV for the third method.

LV and LA volumes and function

CMR provides the most accurate and reproducible assessment of LV volume and ejection fraction and LA volume. All measurements should be indexed to BSA, and remodeling can be assessed based on existing reference values.[158],[159]

When is CMR indicated?

The primary indication of CMR is the evaluation of MR severity when assessment by echocardiography is felt to be unsatisfactory or when there is a discrepancy between MR severity and clinical findings. CMR may provide additional information about the mechanism of MR and myocardial viability, both of which may have implications for surgical intervention, and CMR importantly provides quantitative evaluation of chamber size, RVol, and fraction.

Concordance between echocardiography and CMR

As CMR is increasingly used in evaluating MR and is usually performed after an initial echocardiogram, it is important to review the concordance of evaluating MR severity between these two modalities and what to expect clinically, even with technical adequacy of both studies. There is a paucity of comparative studies, and the majority have shown a modest concordance in the qualitative or quantitative evaluation of MR.[85],[139],[160],[161],[162] This is expected in view of the various factors that affect evaluation of regurgitation by each modality. Reproducibility of quantitation has been consistently higher with CMR. In a recent study, echocardiographic grading of MR severity was higher, and 2D PISA-derived RVols were larger than by CMR.[161] More recently, however, using volumetric pulsed Doppler flow quantitation, a modest correlation was seen between RVol/fraction by echo and CMR, without a consistent over estimation by either modality, similar to previous studies.[162] Exact concordance of semiquantitative grading of MR (four-grade scale) was seen in 50% of patients, increasing to 90% when allowing for a one grade difference in MR severity.[162] The majority of the discrepancies in assessing MR occurred in secondary MR, where RVols are small and more subject to errors. It is important to note that while CMR is more reproducible, each modality has its potential errors and limitations and is technically demanding. In the 10%-20% where a significant discrepancy in assessment of MR between these modalities occurs[162] and may be important clinically, further assessment would be required with either TEE or invasive means if reconciliation of findings (e.g., problem with one technique or the other, interim physiologic changes, rhythm disturbance, etc.) cannot be achieved.

Integrative approach to assessment of MR

Evaluation of MR severity ideally integrates multiple parameters because all methods have intrinsic limitations and lack precision. It is also important to distinguish between the amount of MR and its hemodynamic consequences. For example, a modest RVol that develops acutely into a small, noncompliant LA may cause severe pulmonary congestion and systemic hypotension.

Conversely, some patients with chronic severe MR remain asymptomatic owing to compensatory mechanisms and a dilated, compliant LA. It is important to consider primary and secondary MR separately, as the etiology, mechanism, underlying cardiac structures, and hemodynamics differ significantly and may modulate echo/Doppler parameters assessing MR. However, regardless of etiology, if there is a small central jet, normal leaflet morphology, a VCW <0.3 cm, no proximal flow convergence, and an A-wave dominant mitral inflow pattern, then MR is mild and further quantitation is not necessary. Conversely, if there is a large jet, with a prominent flow convergence, large VCW >0.7 cm, flow reversal in the pulmonary veins, then MR is severe; quantitation would substantiate the severity of the regurgitation.

The qualitative, semiquantitative, and quantitative parameters used in grading primary MR are summarized in [Table 8], along with a suggested algorithm for the assessment of MR severity [Figure 18] that incorporates these various parameters. In applying this scheme, the writing committee wishes to emphasize that specific signs have inherently a high positive predictive value for the severity of regurgitation and are thus highlighted in bold in [Table 8]. The supportive signs or clues may be helpful in consolidating the impression of the degree of MR, although their predictive value is more modest. It is the consensus of the committee members that the process of grading MR should be comprehensive, using a combination of clues, signs, and measurements obtained by Doppler echocardiography. If the MR is definitely determined as mild or less using these signs, no further measurement is required. If there are signs suggesting that the MR is more than mild and the quality of the data lends itself to quantitation, it is desirable for echocardiographers with experience in quantitative methods to determine quantitatively the degree of MR, including the RVol and fraction as descriptors of volume overload and the EROA as a descriptor of the lesion severity. Quantitation of regurgitation can further subclassify regurgitation into four grades, with grade III having some overlap with characteristics of severe MR [Figure 18] and [Table 8], hence the need for an integrative approach. Finally, it is important to stress that when there is congruent evidence from different parameters, it is easy to grade MR severity with confidence. When different parameters are contradictory, one must look carefully for technical and physiologic reasons to explain the discrepancies and rely on components with the highest quality of the primary data that are the most accurate, considering the underlying physiologic condition. There will be times when MR severity and/or mechanism is uncertain by TTE and further testing is needed with TEE or CMR. The following are some considerations in the assessment of severity of primary and secondary MR:
Table 8: Grading the severity of chronic mitral regurgitation by echocardiography

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Figure 18: Algorithm for the integration of multiple parameters of mitral regurgitation severity. Good-quality echocardiographic imaging and complete data acquisition are assumed. If imaging is technically difficult, consider transesophageal echocardiography or cardiovascular magnetic resonance. Mitral regurgitation severity may be indeterminate due to poor image quality, technical issues with data, internal inconsistency among echo findings, or discordance with clinical findings

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Considerations in primary MR

Severe valve lesions on 2D or 3D imaging, such as flail leaflet, ruptured papillary muscle, severe leaflet retraction, or a large perforation, are specific for severe MR. Similarly, a properly measured VCW ≥ 0.7 cm is specific for severe MR, as is systolic flow reversal in more than one pulmonary vein. In contrast, failure to identify a proximal flow convergence region or the presence of an A-wave dominant mitral filling pattern are specific for nonsevere MR. Proper integration of the many echocardiographic findings include appropriate discounting of measurements that may not be considered accurate for technical reasons. As noted earlier, it is critical to pay attention to the duration of MR as late systolic MR is rarely severe. The hemodynamic consequences of MR are reflected in several parameters including LA and LV volumes, the contour of the CWD profile, and pulmonary venous flow pattern. Finally, clinical presentation and hemodynamic state should also be considered in making a final judgment of MR severity.

Considerations in secondary MR

Secondary MR can be much more challenging to grade than primary MR. The challenge arises from several situations as alluded to earlier in Section II, General Considerations: the total LV forward SV may be reduced and thus RVol is usually lower than in primary MR (below 60 mL for severe MR if total SV is reduced). Although RF would account for comparative lower flows, its derivation has higher errors because of the small numbers involved.[46],[162] The regurgitant orifice is frequently semilunar or elliptical, affecting measurements of VCW and possibly leading to underestimating EROA by the 2D PISA method. EROA may also vary with LV size and LVEF.[163] Thus while EROA ≥ 0.4 cm2 still denotes severe MR, a lower cutoff of EROA ≥ 0.3 cm2 may still be likely severe MR by 2D PISA due to the above considerations. Adding to the challenges of secondary MR, adjunctive findings are less helpful because they are often rendered abnormal by the underlying cardiomyopathy. For example, most patients with cardiomyopathy have systolic blunting of the pulmonary venous flow pattern due to elevated LA pressure. Because of a combination of elevated LA pressure, a dilated and compliant LA, and depressed LV systolic function, systolic flow reversal is not commonly seen, even though it remains specific for severe secondary MR when present. Another confounding problem is that secondary MR is notoriously dynamic [Figure 15]. It is important to consider volume status, blood pressure, and other clinical variables, as in primary MR.

Several studies have shown that EROA ≥ 0.2 cm2 portends a worse prognosis in secondary MR.[136],[137],[164] Considerable controversy has arisen regarding whether EROA ≥ 0.2 cm2 by 2D PISA should redefine severe secondary MR based on prognosis alone.[163],[165],[166] In fact, this criterion has been incorporated in the last ACC/AHA guidelines.[1] This issue and how to address secondary MR was deliberated on and discussed extensively among the writing committee members. The rationale for the current recommendations regarding EROA is as follows. If association with adverse prognosis warrants labeling a lesion as severe, then any degree of secondary MR should be considered clinically significant, since there is evidence that even mild MR is associated with adverse prognosis.[167],[168] It is not clear whether the prognostic value of EROA ≥ 0.2 cm2 is primarily due to the MR itself or to the underlying LV dysfunction or degree of myocardial scarring and irreversible damage. Importantly, there is no evidence that surgical correction of secondary MR improves outcomes,[1] and there is concern that calling lesser degrees of MR as severe might lead to unnecessary intervention. In fact, recent data have shown that MV repair of moderate ischemic MR (using an integrative approach, inclusive of EROA 0.2-0.39 cm2) did not improve outcome and was associated with an increased hazard of neurologic events and supraventricular arrhythmias.[169] Finally, in patients with severe MR treated with the MitraClip, reduction of MR severity was associated with favorable LV and LA remodeling and improved functional class, even when residual MR was moderate.[142] Redefining such MR as severe based on EROA is problematic, unless improvement in remodeling and outcome can be shown for catheter-based interventions on traditional moderate MR. Further research is needed to refine severity criteria in secondary MR using 2D and 3D echocardiography, address the role of CMR, and assess whether LV and LA reverse remodeling occurs, along with improved clinical outcome when intervening on patients with various cutoff values of regurgitation severity. This will likely be facilitated by the advent of catheter-based techniques of MV repair and replacement.


  Aortic Regurgitation Top


Anatomy of the aortic valve and etiology of aortic regurgitation

The aortic valve is composed of three semilunar cusps attached to the aortic wall and forming in part, the sinuses of Valsalva. The highest point of attachment at the leaflet commissures defines the sinotubular junction, and the most ventricular point (i. e., the nadir of the cusps) defines the annular plane.[170] The coaptation zone of the leaflets (lu-nulae) are more uniform in thickness except for a slightly more fibrous region at the anatomic midpoint of each cusp or nodules of Arantius.[171],[172] Given the anatomy of the aortic valve, AR results from disease of either the aortic leaflets and/or the aortic root [Table 9] that results in valve malcoaptation.[173]
Table 9: Etiology and mechanisms of aortic regurgitation

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In congenital bicuspid aortic valve, all combinations of conjoined cusps can be identified by TTE; visualization of the raphe is key to classification of bicuspid valve types.[174],[175] Because of the increased stress on the typically larger conjoined cusp, these valves may become stenotic, regurgitant, or both. In addition, AR may be seen secondary to the associated dilatation of the aorta.[176],[177],[178] TTE has up to a 92% sensitivity and 96% specificity for detecting bicuspid valve anatomy.[179]

Classification and mechanisms of AR

Identifying the mechanism responsible for AR is essential in determining the reparability of the aortic valve. Several functional classifications can be used. Adaptation of the Carpentier classification originally designed for the MV[94] have been described for AR[180] and can be helpful to understand the mechanism of AR, guide valve repair technique, and predict recurrence of AR [Figure 19].[181] This scheme classifies dysfunction based on the aortic root and leaflet morphology. Type I is associated with normal leaflet motion and can be subcategorized based on the exact pathology of either the aortic root or valve. Type Ia occurs in the setting of sinotubular junction enlargement and dilatation of the ascending aorta, type Ib is a result of dilatation of the sinuses of Valsalva and the sinotubular junction, type Ic is the result of dilatation of the ventriculoarterial junction (i.e., the annulus), and type Id results from cusp perforation or fenestration without a primary functional aortic annular lesion. Type II is associated with excessive leaflet motion from leaflet prolapse as a result of either excessive leaflet tissue or commissural disruption. Type III is associated with restricted leaflet motion seen with congenitally abnormal valves, degenerative calcification, or any other cause of thickening/fibrosis or calcification of the valve leaflets.
Figure 19: Suggested classification of aortic regurgitation morphology,[181] depicting the various mechanisms of aortic regurgitation. Type Ia depicts sinotubular junction enlargement and dilatation of the ascending aorta. Type Ib depicts dilatation of the sinuses of valsalva and sinotubular junction. Type Ic depicts dilatation of the ventriculoarterial junction (annulus). Type Id denotes aortic cusp perforation

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Assessment of AR severity

Echocardiographic imaging

Echocardiography plays an important role in the overall assessment of AR and in the timing of surgical intervention.[1] While “physiologic” or mild degrees of tricuspid and PR are commonly noted in normal exams, AR is not. When AR is detected, the evaluation starts with an assessment of the anatomy of the aortic valve and root to determine the etiology of the regurgitation followed by an assessment of LV size, geometry, and function. Similar to MR, the hemodynamics and cardiac adaptation to acute versus chronic AR are quite different. In severe acute AR, the LV is not dilated and the sudden rise in LV end-diastolic pressure may cause the MV to close prematurely, best documented with an M-mode. In chronic AR, echocardiography is essential in tracking the changes in LV geometry (progressive increase in LV volume) and function (progressive worsening) due to the protracted LV volume overload. LV dilatation, particularly with preserved LV function, is a supportive sign of significant AR and becomes more specific with exclusion of other causes of LV volume overload (e. g., athlete, anemia). Stress echocardiography can be utilized in both asymptomatic and symptomatic patients to assess functional capacity, the presence of coronary disease, and response of LV size and function to exercise.

Doppler methods

Doppler echocardiography is essential in the evaluation of AR severity. The underlying principles for color flow Doppler, pulsed, and CWD in the assessment of valve regurgitation have been discussed earlier under Section II, General Considerations. The various methods in assessing AR, their advantages and limitations are detailed in [Table 10]. [Table 11] summarizes the parameters involved in grading the severity of AR.
Table 10: Doppler echocardiography in evaluating severity of AR

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Table 11: Grading the severity of chronic aortic regurgitation with echocardiography

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Color flow Doppler

AR in most patients is easily seen with color flow Doppler as a mosaic blend of colors originating from the aortic valve during diastole. Although the apical approach is the most sensitive for detection, the parasternal long and short axis are essential in evaluating the origin of the jet and its semiquantitative characteristics. It is important to visualize the three components of the color jet (flow convergence, VC, and jet area) for a better assessment of the origin and direction of the jet and its overall severity [Figure 20]. Because the length of the AR jet into the LV chamber is so dependent on the driving pressure (diastolic blood pressure), it is not a reliable parameter of AR severity. Lastly, AR usually lasts throughout diastole except in acute AR, where it may be brief and of lower velocity, making detection and assessment with color Doppler more difficult.
Figure 20: Color flow Doppler of aortic regurgitation in the parasternal long- and short-axis views. The three components of the jet are shown with arrows: Flow convergence, vena contracta, and jet height (or width) in the left ventricle outflow

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Jet width in LVOT: the width of the AR jet compared with the LVOT diameter in centrally directed jets can be used to assess the severity of regurgitation semiquantitatively. This ratio is obtained in the parasternal long-axis view, just apical to the aortic valve. A ratio <25% generally indicates mild, 25%-64% indicates moderate, and ≥65% indicates severe AR. Similarly, a ratio of the area of the jet in cross section (short-axis view) to LVOT area is a measure of AR severity [Table 10] and [Table 11]. However, both the width and area ratios are not valid in eccentric jets, directed towards the septum or anterior MV, or in multiple jets.

Vena contracta: the VC is best visualized and measured in a zoomed, parasternal long-axis view. Since it is the narrowest area of the jet, it is smaller than the jet width in the LVOT. It can be measured in most patients with good echocardiographic images. A VC <0.3 cm indicates mild, 0.3-0.6 cm indicates moderate, and >0.6 cm indicates severe AR. If optimized, VC can still be measured in most eccentric jets. The VCW is small, so errors in measurement of 2 mm or more can influence AR grading.

Flow convergence (PISA): flow convergence can be used qualitatively and quantitatively for evaluation of AR severity [Figure 21], similar to MR. Zooming on the LVOT in either the parasternal or apical long-axis views is the best approach to record the proximal flow convergence area, with a baseline shift of the Nyquist limit to measure the flow convergence radius. Measurement of the AR peak velocity and VTI by CWD allows calculation of the EROA and RVol [see earlier and [Table 10]. The threshold for severe AR is an EROA ≥ 0.30 cm2 and an RVol greater than 60 mL [Table 11]. Clinically, PISA quantitation of AR is used less often than in MR, as the flow convergence is in the far field and may be shadowed by aortic valve thickening and calcifications. Imaging from the right parasternal window may be helpful.[182]
Figure 21: Flow convergence or proximal isovelocity surface area can be performed for obtaining the Effective regurgitant orifice area in patients with aortic regurgitation. Zooming in on the left ventricular outflow tract in either the parasternal or apical long-axis views is the best way to record the proximal flow convergence area. Adjust the Nyquist limit using the baseline shift control to obtain and measure the flow convergence radius (red arrow). Regurgitant flow rate is calculated as 2π × r2× VAlias (r = the radius of the flow convergence in early diastole [red arrow], and VAlias is the Va in cm/sec). Effective regurgitant orifice area and regurgitant volume can then be calculated as EROA = regurgitant flow rate/peak aortic regurgitation velocity in early diastole in cm/sec. RVol = EROA × VTI of the aortic regurgitation. For the aortic valve, severe regurgitation is an Effective regurgitant orifice area greater than 0.30 cm2 and an regurgitant volume greater than 60 mL

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Pulsed wave Doppler

Aortic diastolic flow reversal: pulsed wave Doppler from the suprasternal window in the descending aorta often shows a brief early diastolic flow reversal in normals. Holodiastolic flow reversal is an abnormal finding [Figure 22] and indicates at least moderate AR; when present in the abdominal aorta, it is consistent with severe AR. However, in the absence of AR, holodiastolic retrograde aortic flow can also be seen in other conditions such as a left-to-right shunt across a patent ductus arteriosus, reduced compliance of the aorta in the elderly, an upper extremity arteriovenous fistula, a ruptured sinus of Valsalva, or when there is an aortic dissection with diastolic flow into the false lumen. Note that in acute severe AR or bradycardia, there may be equilibration of pressure between the aorta and ventricle before the end of diastole leading to flow reversal that is not holodiastolic. The ratio of the VTI of the reverse flow to the forward flow provides a rough assessment of RF. Variation in aortic size during the cardiac cycle limits this from being a truly quantitative measure.
Figure 22: (a) Still frame of a patient with moderate eccentric aortic regurgitation due to aor tic valve prolapse. Note the area of flow convergence and vena contracta. (b) Early closure of the mitral valve (before the R wave of the electrocardiogram) in a patient with acute aortic regurgitation due to bacterial endocarditis. (c) Pulsed Doppler in the descending aorta in a patient with severe aortic regurgitation depicting holodiastolic aortic flow reversal. (d) Continuous wave Doppler of a patient with severe and acute aortic regurgitation. Note the steep deceleration slope and similar density of the antegrade and retrograde flows

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Flow calculations: quantitation of flow with pulsed Doppler for the assessment of AR is based on comparison of measurements of aortic SV at the LVOT with mitral or pulmonic SV, provided there is no significant MR or PR. Grading of AR severity with RVol and RF is shown in [Table 11]. EROA can also be calculated by dividing the RVol by the VTI from AR CWD jet recording. Total LV SV (equal to SV at LVOT in isolated AR) can also be obtained from the difference between LV diastolic and systolic volumes. The use of 3D echocardiography and contrast enhances the accuracy of this measurement and decreases the underestimation of total LV SV by echocardiography. As noted in the general section, meticulous attention to accuracy is needed throughout this process, and even then, the confidence intervals may remain wide.

Continuous wave Doppler

The best window for the evaluation of AR with CWD is the apical window. However, in very eccentric jets, identified by color Doppler, a parasternal window may give a better ultrasound alignment and recording of the jet.

Signal density: the density of the CWD signal reflects the volume of regurgitation, particularly when compared to the density of the forward flow. A faint or incomplete jet indicates mild or trace regurgitation, while a dense jet may be compatible with more significant regurgitation but cannot differentiate between moderate and severe AR.

Pressure half-time: the pressure half-time of the AR spectral Doppler slope can be a parameter of severity. The CW signal has to be adequate with a clear visualization of the decrease in diastolic AR velocity for this measurement to be performed. A steep slope indicates a more rapid equalization of pressures between the aorta and LV during diastole [Figure 22]. A pressure half-time >500 msec suggests mild AR, and <200 msec suggests severe AR. However, since this parameter is affected by compliance of the LV, patients with severe chronic regurgitation with well compensated ventricular function may have a pressure half-time in the “moderate” range. In contrast, mild AR in patients with severe diastolic dysfunction may have short pressure half-time. The pressure half-time reflects reduction in the transvalvular gradient, which can also be accomplished by vasodilator therapy (reduces diastolic blood pressure independent of the AR). Thus, this method is less useful for monitoring AR in patients being treated medically.[183],[184]

Role of TEE

TTE is an essential first diagnostic test[84] and is frequently sufficient to evaluate the presence and severity of AR. TEE is usually reserved for more detailed assessment, if needed, of the morphology of the valve and aorta, mechanism of AR, and measurements of color flow parameters. Both 2D and 3D TEE have proven utility, improving diagnostic accuracy of TTE in a number of disease processes causing AR: infectious or inflammatory endocarditis,[185],[186] isolated aortic root dilatation,[187] or acute aortic dissection.[188],[189] The diagnostic value of 2D and 3D TEE in defining the mechanisms of AR is particularly important for presurgical evaluation of patients undergoing aortic root surgery,[190] valve-sparing aortic surgery,[191] or valve repair.[192],[193],[194] Understanding leaflet as well as aortic root morphology will likely be more important in the planning of transcatheter repair or replacement devices.[195],[196]

Role of CMR in the assessment of AR

There are four main roles for CMR in the assessment of AR: identification of the mechanism of AR, quantification of its severity, evaluation of LV remodeling, and potential associated aortopathy:

Mechanism

Anatomic assessment of the aortic valve and aortic root is typically performed with the use of cine SSFP sequences [Figure 23]. An imaging plane is prescribed to produce a standard three-chamber long-axis view and additionally an LVOT coronal view.[69] These views are then used to prescribe a parallel series of at least 3 thin (4-5 mm) slices in short axis and provide a comprehensive assessment of aortic valve and aortic root anatomy and can aid in identifying congenital leaflet anomalies (i.e., bicuspid), acquired leaflet abnormalities (i.e., vegetations), or aortic root or ascending aortic abnormalities [Figure 23].
Figure 23: Examples of various etiologies of aortic regurgitation identified with cardiovascular magnetic resonance: Bicuspid aortic valve (a), vegetation on the aortic valve (b), aortic root dilation (c), and type A aortic dissection (d)

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There are limitations of cine CMR that need to be mentioned. Specifically, while the in-plane resolution is high (typically 1.5 mm), the slice thickness is 4-5 mm, which can lead to some partial volume effects. Additionally, since cine CMR images are acquired over multiple cardiac cycles, there may be difficulty in visualizing highly mobile objects such as small mobile vegetations. Nonetheless, CMR can still provide useful insights into the mechanism of AR in most cases.

Quantifying AR with CMR

There are several methods for quantifying AR by CMR, broadly categorized as direct and indirect methods (see Section II, General Considerations). The direct method involves performing phase-contrast velocity mapping in a plane perpendicular to the aorta; most operators recommend positioning in the aortic root (just above the aortic valve)[197],[198],[199] [Figure 7] and [Figure 24]. Forward and reverse flow is derived by integrating the velocity of each pixel and its area over the cardiac cycle.[6],[200] This information can then be used to calculate RF (reverse volume/forward volume × 100%). In most instances this direct method is the preferred technique for assessment of AR as it is the most validated and is not affected by coexisting valvular regurgitant lesions.[80],[160],[201],[202],[203]
Figure 24: Phase-contrast cardiovascular magnetic resonance for assessment of aortic valve flow. (a) Phase-contrast cardiovascular magnetic resonance acquisition is prescribed in a plane perpendicular to the aortic root, just above the aortic valve (yellow dashed line). This produces two sets of images on which contours of the aortic wall are planimetered (red contours in panels b and c): Magnitude images that provide anatomic location information (b) and phase image that encodes velocity in each pixel (c). A flow-time curve is generated (d) by integration of velocity and area data at each phase in the cardiac cycle. The reverse (regurgitant) volume is 70 mL, and the regurgitant fraction is 70 mL/138 mL or 51%

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Occasionally in the setting of arrhythmias or atrial fibrillation, the data obtained from the direct method may be compromised (specifically the diastolic reverse flow assessment). In these instances, multiple indirect methods can be employed to determine AR severity. In the absence of significant PR, aortic RVol can be derived by subtracting the pulmonic forward flow from the aortic forward flow.[204] Another indirect method involves comparing the RV and LV SVs obtained by planimetry;[205],[206],[207] however, it will not be reliable if there is significant coexisting mitral or right-sided regurgitant lesions.

In addition to volumetric quantification, a number of features have been evaluated as corroborating signs of severe AR. The ARO can be determined by obtaining an ''en face'' view of the aortic valve using sequential SSFPs cines. The smallest diastolic regurgitant orifice in middiastole is traced. An ARO ≥ 0.48 cm2 was found to have a sensitivity and specificity of 83% and 97%, respectively, in detecting severe AR.[76] In a separate study, the presence of holodiastolic flow reversal in the mid descending aorta predicted severe AR with high sensitivity (100%) and specificity (93%).[208]

LV remodeling

LV remodeling could be a consequence of chronic severe AR and may be a specific marker of regurgitation severity. CMR provides the most accurate measurement of LV volumes. This is accomplished using the acquisition of short-axis SSFP cine images from the base to the apex of the ventricle followed by endocardial contouring with commercially available software. Recently a study focused on prognosis demonstrated that an LV volume of >246 mL (unindexed) predicted progression to symptoms or the need for aortic valve replacement over a mean follow-up of 2.6 years.[86]

Aortopathy

The presence of aortopathy can be a cause of AR or associated with AR. It is reliably assessed using contrast and non-contrast magnetic resonance angiography techniques.

When is CMR indicated?

While echocardiography remains the first line modality for assessment of AR, CMR is indicated in the following situations: (1) suboptimal echocardiographic images; (2) discordance between echocardiographic and Doppler findings (i.e., discordance between LV enlargement and Doppler measures of AR severity); or (3) discordance between clinical assessment and severity of AR by echocardiography;[209] (4) patients with moderate or severe AR and suboptimal echocardiography for assessment of LV volumes and systolic function and measurement of AR severity;[209] (5) patients with bicuspid aortic valves, when the morphology of aortic sinuses, sinotubular junction, or ascending aorta (to at least 4 cm above the valve plane) cannot be assessed accurately or fully by echocardiography.[209],[210] Lastly, the direct method for AR quantification described in this section is independent of other coexisting valvular lesions, and therefore CMR may be used in the setting of multiple valvular lesions when echocardiographic assessment may be challenged. This will be presented in more detail in the section on multivalvular disease.



CMR measurement of regurgitant severity of AR and accompanying LV remodeling is less variable than with echocardiography and may therefore be ideally suited for longitudinal follow up in individual patients.[160] Furthermore, patients with bicuspid aortic valves, concomitant AR, and ascending aortic dilatation may be best followed with CMR, depending on the severity of AR and size of the aorta.

Integrative approach to assessment of AR

The evaluation of AR by Doppler echocardiography should be a comprehensive and an integrative process based on all the information collected during the examination, since each of the parameters used in this evaluation has advantages and limitations [Table 10] and [Table 11]. In all cases one should routinely perform an evaluation of the aortic valve and LV size and function and an assessment of the jet characteristics by color flow imaging. The LV outflow velocity and the velocity in the proximal descending aorta and/or abdominal aorta should be recorded by pulsed Doppler. CWD of the AR jet should also be routinely recorded but only utilized if a complete signal is obtained.

Based on data in the literature and a consensus of the committee members, the writing committee proposes a scheme for evaluation of patients with AR [Figure 25]. In applying this scheme, it is the consensus of the committee members that the process of grading AR should be comprehensive using a combination of these signs, clues, and measurements obtained by Doppler echocardiography. If the AR is definitely determined as mild or severe using these specific signs, no further measurement is required, particularly for mild lesions. If there are only few parameters consistent with mild or severe AR, and the quality of the primary data lends itself to quantitation, it is desirable for echocardiographers with experience in quantitative methods to measure quantitatively the degree of AR, including the RVol and fraction as descriptors of volume overload and the effective regurgitant orifice as a descriptor of the lesion severity. Similar to MR, quantitation of regurgitation can further subclassify regurgitation into four grades, with grade III having some overlap with characteristics of severe AR [Figure 25], hence the need for an integrative approach. Similar to MR, when the evidence from the different parameters is congruent, it is easy to grade AR severity. When different parameters are contradictory, one must look carefully for technical and physiologic reasons to explain these discrepancies and rely on the components that have the best quality of the primary data and that are the most accurate considering the underlying clinical condition. In situ ations where the assessment is difficult and indeterminate, provides contradicting echo/Doppler data that cannot be resolved, or conflicts with the clinical presentation, further testing is advised with either TEE or CMR.
Figure 25: Algorithm for the integration of multiple parameters of aortic regurgitation severity. Good-quality echocardiographic imaging and complete data acquisition are assumed. If imaging is technically difficult, consider transesophageal echocardiography or cardiovascular magnetic resonance. Aortic regurgitation severity may be indeterminate due to poor image quality, technical issues with data, internal inconsistency among echo findings, or discordance with clinical findings. PHT: Pressure half-time

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  Tricuspid Regurgitation Top


A small degree of TR is present in the majority of normal individuals. Hemodynamically significant TR may be responsible for significant morbidity and possibly mortality, independent of underlying conditions.[9],[211],[212] TR may be difficult to detect on clinical examination because the murmur is often soft. It is important for the echocardiographer not only to recognize severe TR but also to try to elucidate its mechanism.

Anatomy of the tricuspid valve

The TV is the largest and most apically positioned valve and its functional anatomy, similar to the MV, can be divided into four components: the fibrous annulus, the three leaflets, the papillary muscles, and the chordal attachments.[213],[214],[215],[216],[217],[218] The tricuspid annulus is complex and dynamic, allowing it to change with varying loading conditions. Unlike the MV, there is no fibrous continuity with the corresponding semilunar valve. Three-dimensional echocardiography has been integral in our understanding of TV anatomy.[217] A normal annulus is triangular as well as saddle shaped [Figure 26].[219] When functional dilatation occurs, the annulus becomes more circular and planar,[220] dilating in the septal to lateral direction.
Figure 26: Three-dimensional echocardiography provides the only echocardiographic approach to visualize the three leaflets of the tricuspid valve simultaneously. A: Anterior leaflet, P: Posterior, S: Septal

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Etiology and pathology of tricuspid regurgitation

The most common cause of TR is secondary or functional regurgitation, due to annular dilatation from either right atrial or RV enlargement. [Table 12] lists the common etiologies of TR. Annular dilation, papillary muscle displacement, or a combination can cause significant TR.[221] This can occur in the setting of RV dysfunction, pulmonary hypertension, or left heart disease. In these conditions, the increased tethering forces result in leaflet malcoaptation and leaflet tethering and tenting.
Table 12: Etiology of tricuspid regurgitation

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The most common cause of primary TR is myxomatous degeneration.[222],[223],[224],[225] Although some degree of prolapse is common for the nonplanar TV, actual “TV prolapse'' is typically reserved for excessive billowing into the right atrium associated with redundancy of the tricuspid leaflets. This abnormality is seen in 20% of patients with concomitant MVP. Flail leaflets are not typically associated with myxomatous TV disease but rather with closed chest trauma[226],[227],[228] or RV endomyocardial biopsy.[229],[230],[231]

Pacemaker leads can result in significant TR by interfering with closure of the TV but rarely cause a flail leaflet or a perforation of the leaflet.[232]

Role of imaging in tricuspid regurgitation

Evaluation of the tricuspid valve

Echocardiographic imaging

A comprehensive TTE examination of the TV requires a methodical approach to identify the pathology associated with TR.[233] With 2D echocardiography, the three leaflets cannot be visualized simultaneously, and there is a great deal of variability as to which leaflets are visualized in a given view. The parasternal RV inflow view will always image the anterior leaflet in the near field, but in the far field, the leaflet may be the septal or the posterior leaflet.[234] On short axis, the leaflet adjacent to the aorta is either the septal or anterior leaflet, and the leaflet adjacent to the RV free wall is usually the posterior leaflet.[217] In the apical four-chamber view, there is more certainty, with the anterior leaflet on the free wall and the septal leaflet adjacent to the septum. Significant annular dilatation is defined by an end-diastolic diameter ≥40 mm or >21 mm/m2 in the four-chamber transthoracic view and is the main imaging criterion used to indicate severe TR in the current the ACC/AHA guidelines.[1] Compared with TTE, TEE is in general more limited in permitting optimal views due to off-angle imaging planes and the greater distance of the probe from the TV. Three-dimensional echocardiography provides unique en face views of the TV that enable simultaneous visualization of all three leaflets and the entire annulus [Figure 26].[3] The addition of color flow Doppler to a full volume acquisition not only provides the ability to analyze the mechanism and locate the TR jet but also to quantify the size of the effective regurgitant orifice size by using cropping planes to display and measure the VCA.

CMR imaging

The normal TV with a thickness of <1 mm[235] is difficult to visualize clearly with routine CMR cine SSFP imaging [Figure 27]. The strengths of CMR in defining tricuspid anatomy include its ability to display the valve in any imaging plane. When the valve is thickened in pathological situations, the valve and TR are more readily visualized by CMR. In a study comparing echocardiography with CMR in patients with Ebstein's anomaly, the posterior leaflets and TV fenestrations were better visualized by CMR.[236] A limitation of CMR that can compromise visualization of TV leaflets is that flow cannot be separated from 2D structural imaging unlike color Doppler in echocardiography. In case of turbulent flow, the turbulence creates flow disturbance, which is of low signal intensity and can obscure the valve and make it difficult to visualize [Figure 28].
Figure 27: Tricuspid valve normal anatomy visualized by cardiovascular magnetic resonance. (a) Basal short-axis view when the tips of the three leaflets can be seen on the same plane (outlined by the black triangle). The relationship with the four-chamber view and right ventricle inflow view are illustrated by the dotted lines. (b) Four-chamber view where the septal and anterior leaflets are seen. (c) The right ventricle inflow (two-chamber) view where the anterior and posterior leaflets are seen. (d) Right ventricle inflow and outflow view (three-chamber view) can visualize posterior and septal leaflets

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Figure 28: Cardiovascular magnetic resonance cine steady-state free precession visualization of mild (a) and severe (b) tricuspid regurgitation. Arrows point to the dephasing jet of tricuspid regurgitation. Severe tricuspid regurgitation may be more difficult to visualize, and the leaflet morphology may be obscured

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Evaluating right heart chambers

The RV is usually dilated in the presence of hemodynamically significant TR. The position of the septum produces a D-shaped LV predominantly in diastole (RV volume overload pattern). When TR is due to pulmonary hypertension, septal flattening is present throughout the cardiac cycle, reflecting the diastolic and systolic overload of the RV (RV pressure overload pattern).

Parameters of RV systolic function are important in following the effects of chronic primary TR to detect deterioration of RV muscle function. RV systolic function is challenging in this setting as these parameters are load dependent. A tricuspid annular excursion measurement <1.6 cm and an RV fractional area change <35% are suggestive of RV dysfunction, although tricuspid annular excursion in particular may yield both false-positive and -negative results.[233] In the presence of an anatomically normal valve, abnormal RV function is more likely the cause rather than the effect of TR. Significant chronic TR also causes enlargement of the right atrium and inferior vena cava. Lastly, right atrial enlargement in patients with permanent atrial fibrillation and concomitant TV annular dilatation (>35 mm) may result in secondary TR.[237]

CMR is currently the reference standard for the quantitation of RV size and function.[238] RV volume and function can be measured using the short-axis stack cine SSFP at the same time when the LV is assessed based on existing recommendations.[6],[69] Dedicated axial orientation cine is not necessary in evaluating the RV in the absence of complex congenital disease.[239] In general, right atrial and RV size measurements are larger by CMR than by echocardiography due to different handling of trabeculations.[158],[240]

Echocardiographic evaluation of TR severity

Color flow imaging

Color flow Doppler evaluation of TR severity involves a critical assessment of the components of the jet: jet area, VC, and flow convergence [Table 13] and [Table 14].
Table 13: Doppler echocardiography in evaluating severity of tricuspid regurgitation

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Table 14: Grading the severity of chronic tricuspid regurgitation by echocardiography

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Jet area

Jet area is one of the color Doppler parameters of regurgitation severity. However, there can be considerable overlap of jet areas in patients with mild versus moderate TR. Furthermore, and similar to MR, regurgitant jets that are eccentric and wall impinging appear smaller than centrally directed jets with similar RVol [Figure 29]. In general, a color Doppler jet area of >10 cm2 is consistent with severe TR; however, since several hemodynamic and anatomic factors affect the appearance of a central jet, jet area is often considered a semiquantitative parameter only. In wide-open, severe TR with no TV coaptation, the TR velocity may be so low that there is no aliasing of the jet velocity and TR may lose its appearance as a distinct jet.
Figure 29: Echocardiographic examples of tricuspid regurgitation cases. In mild tricuspid regurgitation, a small narrow jet is seen with a narrow vena contracta, no flow convergence, and a “faint” tricuspid regurgitation jet on continuous wave Doppler. In severe eccentric tricuspid regurgitation, there is a wide vena contracta and the color flow jet entrains the lateral wall of the right atrium in this patient with a flail septal leaflet; a dense parabolic jet with early peaking is seen. In the severe central tricuspid regurgitation, the vena contracta is >7 mm, with a large flow convergence; continuous wave Doppler demonstrates dense triangulated jet with low velocity (2 m/sec) consistent with severe tricuspid regurgitation and ventricularization of right atrial pressure

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Vena contracta

Visualization of the VCW is technically less demanding than the PISA method and can be utilized either semi-quantitatively or qualitatively. When acquired from the apical four-chamber and RV inflow parasternal views, a TR VCW >0.7 cm identifies severe TR and is a marker of worse prognosis.[29] Three-dimensional color Doppler methods can be used to measure VCA and VCW; however, it is important to note that the imaging planes acquired by 2D and those displayed by 3D may not be identical. In comparing 2D and 3D color Doppler measures of the VC, maximal VC diameter is often larger by 3D Doppler imaging.[241] The 3D VCA correlates well with EROA, moderately well with VC diameter, and weakly with jet area/right atrial area ratio[242] and was best for organic TR and in patients in sinus rhythm. From current available data,[243],[244] a VCA >0.4 cm2 is a reasonable cutoff value for severe TR.

Flow convergence

The proximal convergence method is applicable in TR, but there is less experience with TR than with MR. Quantitation of TR using the PISA method has been validated in small studies[55] but is not commonly used clinically [Figure 30]. The general application is similar to MR. The TR PISA method is subject to all the limitations of its application in MR. In particular, the contour flattening as blood gets closer to the orifice may be exaggerated with TR, since the peak TR velocity is generally less than in MR, thus producing more flattening and regurgitant flow underestimation. To the extent that the orifice is noncircular (as often happens in TR), the usual PISA approach will produce further underestimation. On the other hand, if the TR arises eccentrically, then the proximal convergence zone will be constrained, producing flow overestimation. Using TTE, the 2D PISA method was compared to a single-beat 3D PISA method and to VCA and volumetric derivation of orifice area; EROA derived with 2D PISA underestimated regurgitant orifice area by the other methods.[243]
Figure 30: Measurement of effective regurgitant orifice area and regurgitant volume in a patient with severe tricuspid regurgitation associated with pulmonary hypertension. Severe right atrial enlargement and atrial septal deviation to the left is seen in addition to systolic reversal of hepatic vein flow. D: Diastolic velocity, S: Systolic velocity. Calculations are consistent with severe tricuspid regurgitation

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Regurgitant volume

In theory, TR volume can be calculated by subtracting the flow across a nonregurgitant valve from the antegrade flow across the TV annulus. In contrast to MR and AR, this approach is rarely utilized for TR, partly because of difficulty in accurately estimating the noncircular annular inflow area and the lack of velocity uniformity across the annulus.

The threshold value of RVol for severe TR is unclear. A comparative study in patients with severe MR and TR observed that for the same 2D PISA EROA of ≥0.4 cm2, RVols cutoffs were different for TR (≥45 mL/beat) than for MR (≥60 mL/beat),[244] an obvious consequence of the typically lower TR velocity than MR, suggesting that in clinical practice different thresholds for severe TR and MR may need to be used for RVol, whereas a similar grading scheme can be employed for EROA cutoff. Further confirmation of these findings is needed using volumetric techniques.

Pulsed and continuous wave Doppler

It is important to note that TR jet velocity is not related to the volume of regurgitant flow. In fact, very severe TR is often associated with a low jet velocity (2 m/sec), with near equalization of RV and right atrial systolic pressures [Figure 29]. Similar to MR, the features of the CWD TR jet that help in evaluating severity of regurgitation are the signal intensity and the contour of the velocity curve. With severe TR, a dense spectral recording is seen. A truncated, triangular jet contour with early peaking of the maximal velocity indicates elevated right atrium pressure and a prominent regurgitant pressure wave (“V wave'') in the right atrium [Figure 29]. It should be noted that this pattern may be present in patients with milder degrees of TR and severe elevation of right atrium pressure (reduced right atrial compliance). With severe TR and normal RV systolic pressure, the antegrade and retrograde CW flow signals across the valve can appear qualitatively very similar with a “sine wave'' appearance, corresponding to the “to-and-fro” flow across the severely incompetent valve.

Pulsed wave Doppler examination of the hepatic veins helps corroborate the assessment of TR severity. With increasing severity of TR, the normally dominant systolic wave is blunted. With severe TR, systolic flow reversal occurs [Figure 30]. However, hepatic vein flow patterns are also affected by right atrial and RV compliance, respiration, preload, pacemaker rhythms, complete heart block, and atrial fibrillation and flutter. Systolic flow reversal is a specific sign of severe TR, provided that the modulating conditions mentioned above are accounted for during interpretation.

CMR evaluation of TR severity

CMR assessment of TR is less established compared with other regurgitant valvular lesions. Few indirect quantitative techniques have been used since direct measurement of tricuspid inflow is of limited value (substantial through-plane motion of the TV).[245] RVol can be calculated by subtracting pulmonic forward volume from the RV SV and deriving a RF. Alternatively, in the absence of AR, aortic forward volume can be subtracted from the RV SV. Lastly, in the absence of other regurgitant lesions, LV SV can also be subtracted from RV SV to obtain TR RVol. There are no specific thresholds of RVol for TR severity by CMR. Instead, thresholds for RF have been borrowed from MR classification to grade TR severity (≤15% mild, 16%-25% moderate, 25%-48% moderate to severe, and >48% severe).[85]



Additional qualitative methods to assess TR have been reported using CMR. Visual assessment based on spin dephasing in the right atrium has been used previously.[246] However, newer SSFP sequences, unlike the early spoiled gradient echo sequences, tend to minimize spin dephasing; this is even less appreciated in severe TR and is therefore not recommended to grade regurgitation severity. Time-resolved imaging of contrast kinetics angiography and retrograde hepatic vein contrast appearance have also been used.[247]

The strength of CMR is its ability to quantitatively assess RVol, fraction, and ventricular and atrial remodeling. The limitations of CMR result both from errors in the RV volume assessment and issues in the acquisition of accurate phase-contrast images in the PA. It may be difficult to trace the enlarged trabeculated RV, which can extend above the tricuspid annulus into the atrial plane.[248] Pulmonary outflow and aortic outflow were assessed in patients without an intracardiac shunt and the calculated Qp:Qs was found to be within 0.8-1.2. Therefore a 20% error can exist in either direction in the phase-contrast flow assessment of the PA.[249] In addition, background phase, partial volume average from low spatial resolution and nonperpendicular plane selection, and complex jet flow pattern causing intravoxel dephasing and loss of phase coherence can all lead to inaccurate phase-contrast assessment.[82] Indirect quantification of TR can amplify errors and lead to significant under- or overestimation. In addition, to date, categorization of TR severity by CMR has not been validated due to lack of adequate reference standards.

Integrative approach in the evaluation of TR

The ideal approach to evaluation of TR severity is to integrate multiple parameters of TR severity rather than emphasize or depend on a single measurement. This approach helps to mitigate the effects of technical or measurement errors, which are inherent to each method previously discussed. It is also important to distinguish between the volume of TR and its hemodynamic consequences, particularly when considering acute versus more chronic regurgitation.

The consensus of the committee is to propose an approach to TR evaluation that would first assess the severity of valve regurgitation by evaluating whether there is a majority of specific signs that would point towards either mild or severe regurgitation [Figure 31]. If most of the signs and indices are concordant, then there is confidence in the interpretation and no further quantitation is needed. If the signs or values of the qualitative or semiquantitative parameters are in the intermediate range between mild and severe, most likely the severity of TR is moderate. Although quantitation may be feasible, it is more challenging than in MR and AR; echocardiographers with experience in quantitation may quantitate RVols and EROA to further refine assessment of intermediate lesions; however, clinical experience with these measurements is far less than with MR and AR. Furthermore, in contrast to MR and AR, further subclassifying TR severity into four grades according to quantitative criteria has not been validated in the literature. In the cases where there is difficulty in the evaluation of regurgitation by TTE, significant internal inconsistency (signs of mild and severe TR that cannot be resolved) or discordant findings with the clinical presentation, further evaluation by other modalities may be warranted to more accurately assess the mechanism and severity of TR.
Figure 31: Algorithm for the integration of multiple parameters of tricuspid regurgitation severity. Good-quality echocardiographic imaging and complete data acquisition are assumed. If imaging is technically difficult, consider transesophageal echocardiography or cardiovascular magnetic resonance. Tricuspid regurgitation severity may be indeterminate due to poor image quality, technical issues with data, internal inconsistency among echo findings, or discordance with clinical findings

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  Pulmonary Regurgitation Top


Trace to mild PR, similar to TR, is a common finding and reported to occur in almost 75% of the population[250],[251] and is of little hemodynamic significance. The primary goal of imaging is to identify and assess abnormal degrees of PR, its etiology, and effect on cardiac structure and function.

Anatomy and general imaging considerations

The PV is a semilunar valve with three cusps, located anterior and superior to the aortic valve. The PV cusps are thinner than those of the aortic valve. In the normal heart, the PA arises from a muscular infundibulum and therefore lacks fibrous continuity with the TV.[252] The plane of the PV is orthogonal to that of the aortic valve. Awareness of this spatial relationship is useful when the operator is attempting to define the optimal imaging window for PV imaging. Because the PV is an anterior structure, it offers challenges to imaging, particularly with TEE.

In addition to visualizing the valvular anatomy, the aims of imaging should include inspection of the RVOT, pulmonary annulus, main PA and proximal branches. The annulus and main PA may be dilated in patients with pulmonary hypertension and connective tissue disorders and in some patients with congenital heart disease. The RVOT is often dilated in patients with tetralogy of Fallot whose surgery involved enlargement of the RVOT, usually with a patch. Branch pulmonary stenosis may also contribute to more significant PR.

Etiology and pathology

Primary PR due to abnormal PV leaflets is more common in congenital heart disease and after balloon valvuloplasty for pulmonic stenosis than acquired valve disease. Significant acquired PR is rare, occurring in <1% of patients, and is present in adults with pathologies such as rheumatic heart disease, endocarditis, carcinoid valve disease, or pergolide-induced disease.[253],[254]

Rarely blunt chest trauma can lead to leaflet disruption and prolapse. Secondary PR is most common in patients with elevated PA pressure, although the volume of regurgitation is usually small. By definition, the PV leaflets are normal with secondary PR.

Right ventricular remodeling

Significant primary PR leads to an enlargement of the RV with preserved RV function and a volume overload pattern of the septum. Chronic severe PR may lead to RV dysfunction. However, RV dilation by itself is not a specific sign of significant PR since it can result from a number of conditions, so it is important to correlate RV dilation with the severity of PR by Doppler. Dilation may also be localized to the RVOT as can be seen after a tetralogy repair. In secondary PR, RV dilation and function as well as septal motion relate more to the underlying disease state (e. g., pulmonary hypertension severity) than to the degree of PR, which is usually at most moderate.

Echocardiographic evaluation of PR severity

There is a paucity of data regarding the quantification of PR. This stems partly from the difficulty in visualizing PR, the fact that minor degrees of PR are common and have no clinical impact, and the low incidence of clinically significant PR in the adult. Most of the concepts for quantifying AR are applied to PR. The various parameters used and their advantages and limitations are listed in [Table 15].
Table 15: Doppler echocardiography in evaluating severity of pulmonary regurgitation

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Color flow Doppler

Color Doppler assessment of PR severity includes proximal jet width, color jet area, and jet length [Figure 32].
Figure 32: Examples of mild and severe pulmonary regurgitation depicting the difference in color jet, jet height (between arrows), and spectral density and deceleration of the pulmonary regurgitation jet by continuous wave Doppler. In severe pulmonary regurgitation, there isfrequently early termination of the diastolic regurgitant flow (green arrow) with early equalization of right ventricle and pulmonary artery diastolic pressures

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A jet length of <10 mm is considered to represent insignificant PR,[251] particularly if narrow at the origin; however, as in the case of AR, jet length is sensitive to driving pressure. The jet area has been related to various degrees of PR at angiography; however, significant overlap is seen, and it can be difficult to measure reproducibly. The proximal jet width (VC) is probably the most widely used semiqualitative color Doppler method. This parameter is less dependent on driving pressures and is simple and more reproducible. The VCW of the PR is commonly expressed as a ratio relative to the PV annulus diameter. A ratio of >0.5 is correlated with severe PR measured by CMR.[255],[256] It is important to note that in severe PR with normal PA pressures (e.g., primary PR), the color jet can be difficult to detect as the PR jet velocities are low, laminar, and brief in duration due to rapid equilibration of pressures across the PV. In secondary PR with pulmonary hypertension, the jet is aliased, of high velocity, and usually holodiastolic. There are limited data on the role of 3D echocardiography in assessing PR.[257]

Pulsed and continuous wave Doppler

The density of the CW signal provides a qualitative measure of regurgitation. The CW pattern seen in mild PR shows a soft or faint signal with slow deceleration. In contrast, severe PR has a dense jet with rapid deceleration of the velocity due to the rapid equilibration of the diastolic pressure gradient between the PA and RV [Figure 32] and [Figure 33]. This “to-and-fro'' flow across the PV shows a characteristic “sine wave'' shape. It is important to note that rapid deceleration by itself is not specific for severe PR and can be seen in conditions with decreased RV compliance. Judging the severity of PR in these situations will depend on color Doppler characteristics of the PR jet and comparative flow considerations.
Figure 33: Continuous wave Doppler of pulmonic flow. Calculation of pulmonic regurgitation index (pulmonary regurgitation index = A/B) is shown, an index of pulmonary regurgitation severity, quantitating early termination of diastolic regurgitant flow

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Few indices have been proposed to quantitate the deceleration of the PR velocity and its premature diastolic termination. A pressure half-time of <100 msec (or deceleration time of <260 msec) has been shown to be consistent with severe PR.[258] A PR index has also been suggested, calculated as the ratio of PR duration by CWD to total diastolic time [Figure 33].[259] A PR index of <0.77 was shown to correlate well with severe PR by CMR. However, these indices, as noted, are not specific for severe PR and have to be integrated with other findings in evaluating PR severity.{Figure 33}

An additional sign of severe PR by pulsed Doppler is the presence of reverse flow in the PA. The presence of diastolic flow reversal in the branch pulmonary arteries had a sensitivity and specificity of 87% for severe PR compared with CMR. It is important to visualize and sample flow in the branch pulmonary arteries and not just in the main PA, as the specificity dropped to 39%.[255]

Quantitative Doppler

Quantitative pulsed Doppler methods can be used to measure PR RVol and fraction. The RVOT, however, is probably the most difficult site to measure SV because of its poor visualization and the changing size of the RVOT during the cardiac cycle. The RVOT is measured during early ejection (two to three frames after the R wave on the electrocardiogram) just below the PV in the parasternal short-axis view.[260] Although not validated for quantitation of PR, flows in the RVOT can be compared to other sites to derive RVol and fraction.

CMR methods in evaluating PR

CMR is currently the best method to quantitate PR and serially evaluate RV remodeling and function in patients with significant PR and congenital heart disease.[261] Several approaches can be used to quantify PR by CMR. These can be classified into two broad categories as direct and indirect methods resulting in calculations of RVol and fraction. The methodology of these approaches and their clinical use have been discussed earlier and previously detailed.[6],[69] There is some evidence that pulmonic RVol may better reflect the physiological consequence to the RV than RF.[262],[263] Other CMR techniques such as visual assessment of the degree of signal loss due to spin dephasing from the regurgitation[246] can be used but are less validated and provide only a qualitative assessment.



The direct method based on the use of phase-contrast imaging with acquisition obtained from above the PV [Figure 34] is the preferred method, as it allows direct measurement of total pulmonic forward SV and RVol.[264] The indirect methods are based on SV quantification by ventricular endocardial contouring with or without additional phase-contrast imaging. One method is to use the difference in RV and LV SVs.[245],[263],[265] This technique is only valid in the absence of any other concomitant valvular regurgitation. A second indirect method is to use the difference between RV SV by endocardial contouring and aortic forward SV by phase-contrast imaging to calculate pulmonic RVol. This method is only valid in the absence of TR. Other indirect techniques can be used but are less reliable. The best use of these indirect techniques is to confirm the findings of the direct technique.
Figure 34: An example of severe pulmonary regurgitation (arrow) assessed by cardiovascular magnetic resonance. The red circles depict the magnitude image of the pulmonary artery (upper left panel) and the respective phase contrast image (lower left panel). Forward stroke volume by phase contrast was 129 mL, and reverse (regurgitant) volume was 78 mL, yielding an regurgitant fraction of 60% (lower right panel)

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There are no specific thresholds for PR severity by CMR; as in other regurgitant valves, these have been borrowed from the echo literature. One recommendation for PR severity uses a RF <20% to define mild PR, 20%-40% for moderate, and >40% for severe PR.[266] RVol categories for PR severity by CMR have not been defined.

Integrative approach to assessment of PR

Trivial and mild PR is clinically very common[267] and easily diagnosed. On the other hand, clinically significant PR is uncommon and is usually secondary to pulmonary hypertension and congenital heart disease. Echocardiography is the primary modality for assessment of PR. An integrative approach combining color, pulsed wave Doppler, and CWD methods should be used in the grading of PR. The simplest and most robust method is PR jet width, and VC. Other Doppler measures have limitations, high variability, or limited validation. [Table 16] summarizes the parameters for grading PR. Using these criteria, an algorithm was developed for the assessment of PR and separating mild from severe PR [Figure 35]. If the majority or all criteria point to either mild or severe PR, the evaluation of the severity of PR is confident. If intermediate criteria or an overlap among them is present, the severity of PR is likely moderate. Although quantitation may be feasible, it is more challenging than in MR and AR; echocardiographers may quantitate RVols and fractions to further refine assessment of intermediate lesions; however, clinical experience with these measurements is far less than with MR and AR and likely better obtained with CMR. Furthermore, in contrast to MR and AR, further subclassifying PR severity into four grades according to quantitative criteria has not been validated in the literature. CMR is indicated when there is concern for clinically significant PR that cannot be reliably assessed by echocardiography, when the mechanism for PR is not clear, or when there is a discrepancy between severity by echocardiography and other clinical findings (e.g., only moderate PR with dilating RV). In adolescents and adults with congenital heart disease (e.g., repaired tetralogy, after pulmonary valvotomy) and when there is concern for more than moderate PR, CMR is indicated for quantification and follow-up of PR and RV size and function, especially when intervention such as PV replacement is being considered.[261]
Table 16: Echocardiographic and Doppler parameters useful in grading pulmonary regurgitation severity

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Figure 35: Algorithm for the integration of multiple parameters of pulmonary regurgitation severity. Good-quality echocardiographic imaging and complete data acquisition are assumed. If imaging is technically difficult, consider cardiovascular magnetic resonance or transesophageal echocardiography. Pulmonary regurgitation severity may be indeterminate due to poor image quality, technical issues with data, internal inconsistency among echo findings, or discordance with clinical findings. PHT: Pressure half-time Tables

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  Considerations in Mulitivalvular Disease Top


The presence of multivalvular disease makes the assessment of valvular regurgitation more complex. When evaluating the impact of a second valve lesion on a regurgitant lesion, one must consider in addition to the impact on outcomes, whether the additional lesion modifies the actual severity of the primary lesion and whether it affects the quantitation and grading of the primary lesion. [Table 17] indicates a few of the ways that the assessment of a given regurgitant lesion by Doppler echocardiography or CMR can be impacted by another concomitant valve lesion.
Table 17: Impact of multivalvular disease on assessment of valvular regurgitation with Doppler echocardiography and cardiovascular magnetic resonance

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Impact of multivalvular disease on echocardiographic parameters of regurgitation

Color jet area

A lesion or condition that results in a higher pressure gradient will affect color jet area as detailed earlier under general considerations. For example, the addition of aortic stenosis to MR will increase the RVol in proportion to the square root of the rise in LV pressure, assuming that the EROA remains the same (since jet velocity is related to the square root of the driving pressure gradient). The jet area, however, will be expected to increase more than this, since jet momentum is proportional to regurgitant orifice area × Δp and thus is increased above and beyond the increase in flow. Similarly, any lesion that increases pulmonary arterial pressure will worsen TR by similar amounts, with an exaggerated impact on jet area.

Regurgitant orifice area

Beyond the predictable changes in jet flow with driving pressure, one should also consider whether the second lesion will increase the size of the regurgitant orifice area. Functional MR is particularly prone to this, as the degree of coaptation can vary considerably with LV volume. For example, the further LV dilation from severe AR might increase the regurgitant orifice area in secondary MR and dramatically worsen the RVol. In contrast, one could imagine that a Barlow's-type MV might see a reduction in regurgitant orifice area when AR dilates the LV, making the mitral prolapse less pronounced.

Proximal convergence and vena contracta

PISA and VC methods should generally not be influenced by another regurgitant jet, such as AR. Even in severe MR, the flow convergence region, from which PISA calculations are made, is usually within 1.5 cm of the mitral orifice. Unless AR is markedly eccentric directed posteriorly (e.g., a flail right coronary cusp), the AR jet is not likely to interfere with the flow convergence of the MR. One exception would be if the AR flow is severe enough that the forward flow through the LVOT “contaminates” the proximal convergence flow, pushing the aliasing radius outward. A potential solution for this is to increase the Va, so that the MR PISA is clearly separated from the LVOT flow. The same general observation applies to VC methods, whether using a simple long-axis VCW or the more elegant 3D planimetry of the VCA described previously. There should be little direct impact on VC from a second valvular lesion.



Volumetric methods

All the volumetric methods for quantifying valvular regurgitation require a reference SV against which flow through regurgitant valves can be compared. For example, in isolated MR, LVOT flow could be used as the reference SV. The forward plus mitral RVol could be obtained by either the difference in LV end-diastolic volume and LV end-systolic volume obtained from 2D or 3D echo or by using PW Doppler to measure the SV through the mitral annulus. Subtracting LVOT SV from either of these “mitral” SVs will yield the mitral RVol. However, if AR ensues, then there is no measurement in the left heart that reflects pure systemic flow, as the LV SV includes both the AR and MR RVols. In such a case, one should seek a reference volume in the right heart, most commonly the RVOT, as the TV annulus site is challenging. Unfortunately, if all four valves have important regurgitation, or a shunt is present from an atrial or ventricular septal defect, then there may simply be no reference systemic SV to use. In such cases, direct measurement of forward and reversed flow through a given valve is the best option. Currently, this is most reliably performed with velocity encoded magnetic resonance imaging (see below), although there is hope that 3D echo could do this as well.

CMR approach to quantitation of regurgitation in multivalvular disease

CMR methods for the quantification of valvular regurgitation can offer advantages over other methods in the setting of multivalvular disease. For example, the direct method of AR volume assessment via forward and reverse flow measurements in the aortic root is generally not affected by aortic stenosis, mitral stenosis or regurgitation, or right-sided valvular lesions. It is important to note that in the setting of concomitant aortic stenosis, the aortic forward flow may be underestimated (due to intravoxel dephasing from the stenotic jet).[268],[269],[270] Although the aortic reverse volume assessment would not be affected, it will be useful to utilize the forward flow proximal to the lesion (i.e., LVOT) for the purposes of calculating RF.[268],[270] The principles discussed would also apply to the assessment of PR in the setting of concomitant valvular lesions. [Table 17] highlights conditions where acquisition or quantitation of RVol and fraction would be different than discussed earlier.

The preferred indirect method for deriving mitral RVol (LV SV-aortic forward SV) will be unaffected by coexisting AR (as both LV SV and aortic forward SV will be increased by the amount of AR). However, calculation of mitral RF will require subtracting the AR RVol from the LV SV. Therefore mitral RF in combined MR and AR would be derived by the following: MR RVol/(LVSV − AR RVol) × 100. As the preferred method for TR assessment is analogous, the principles discussed would also apply to TR assessment in the setting of concomitant valvular lesions.

It is important to note, however, that alternative methods for quantifying regurgitation (aside from the preferred methods detailed above) that are often used as confirmatory checks may not be valid in the setting of multiple valvular lesions. Furthermore, assessments of regurgitant severity could be affected in the setting of intracardiac shunt lesions.

As there is a paucity of data on indications for CMR in the setting of multiple valvular lesions, it is reasonable to consider CMR for scenarios as outlined. Owing to the fact that CMR methods are generally independent of other valvular lesions, it may in fact be the preferred method in these situations. Additionally, CMR may be especially useful in the setting of mixed valve disease to fully determine the consequences of multiple lesions on cardiac morphology and function.


  Integrating Imaging Data With Clinical Information Top


The optimal management of patients with valvular regurgitation requires excellent clinical judgment as well as excellent imaging skills. As irreversible LV or RV dysfunction can develop with these lesions before the onset of significant symptoms, it is possible to wait too long before referring patients for surgery or, in some cases, transcatheter intervention. It is also possible to overestimate severity of regurgitation and operate too early in the natural history, thus subjecting patients to the short-term risks of surgical complications and long-term risks of prosthetic valves when they otherwise might have done well without surgery for many years. Thus, accurate quantification of RVols and their hemodynamic impact are of paramount importance.

Data regarding the presence and severity of valvular regurgitation, whether obtained by echocardiography or CMR, need to be interpreted in context with the clinical presentation. Common scenarios include asymptomatic patients with newly diagnosed heart murmurs, patients with known valve disease undergoing serial imaging studies to assess severity of regurgitation and its hemodynamic impact, and patients with heart failure undergoing imaging to assess LV function in whom secondary MR may be suspected or unsuspected. Valvular regurgitation is also often identified as an incidental finding when imaging is performed for other purposes, such as patients after myocardial infarction or patients receiving chemotherapy, in whom previously undetected MR may result from LV systolic dysfunction or be unrelated. Significant but previously unrecognized TR is often detected during evaluation of patients with chronic MR and will require attention if MV surgery is recommended. Similarly, severe PR may be relatively silent for many years in patients following repair of tetralogy of Fallot and other congenital diseases. The indications for and frequency of imaging vary depending on the stages of the disease process as defined in the 2014 AHA/ACC guidelines for management of valvular heart disease[1]: stage A, individuals without known disease but at risk for valvular regurgitation (such as patients with bicuspid aortic valves, MVP, previous rheumatic fever, previous myocardial infarction or dilated cardiomyopathy, previous repair of congenital heart disease); stage B, patients with asymptomatic mild to moderate valvular regurgitation with preserved LV or RV function; stage C, patients with asymptomatic severe valvular regurgitation (C1, normal ventricular systolic function; and C2, depressed ventricular systolic function); and stage D, symptomatic patients with severe valvular regurgitation.



Clinically significant MR almost always produces a systolic murmur, and the characteristics of the murmur should be taken into consideration in image interpretation. For example, a mitral murmur that is late systolic in timing rather than holosystolic suggests that the MR is not severe, in which case the timing of the Doppler signal may be more important than the magnitude of the VC and the calculated EROA by PISA in assessing overall severity of MR. An MR murmur that radiates to the posterior thorax is almost always indicative of severe MR; in such cases an eccentric MR jet may be difficult to quantify but the physical findings may prompt additional ancillary imaging findings such as LA dilation and reversal of systolic flow in the pulmonary veins. Symptomatic patients with apparently mild or moderate MR on resting echocardiographic studies, in whom the MR murmur changes dramatically with interventions such as the Valsalva maneuver or standing from a squatting position, may be candidates for exercise Doppler interrogation to determine whether exercise-induced symptoms correlate with worsening of MR. Patients with LV dysfunction and secondary MR often have very soft murmurs even when the MR is severe, and an apical systolic murmur of any magnitude on physical exam in a patient with known LV systolic dysfunction should raise the possibility of clinically significant secondary MR. It is also important to recognize that even mild degrees of MR, which would be well tolerated for years in patients with primary MR, identify patients at considerable risk of heart failure and death in the setting of LV dysfunction and secondary MR.

In contrast, the diastolic murmur of AR is often barely audible or may be completely absent, and the only appreciable murmur may be a systolic outflow murmur related to the high SV. Additional physical findings such as a wide pulse pressure or bounding carotid pulses point toward significant AR rather than AS. AR is often first identified on echocardiograms performed to investigate a systolic murmur.

Similarly, TR is also often not identified clinically prior to echocardiography but identified as an important concomitant lesion in patients with MR. When TR results from primary disease of the TV, there are often no clinical manifestations when the TR is mild. However, severe TR caused by primary disorders is almost invariably associated with a systolic murmur with respiratory variation, elevated V waves in the jugular venous pulse, and an RV heave as evidence of RV volume overload. PR in the setting of normal PA pressure, such as following repair of tetralogy of Fallot, can go unrecognized as the murmur is usually soft and low pitched, whereas PR related to pulmonary hypertension creates a higher pitched murmur that is difficult to distinguish from AR.

As the clinical management of patients with severe MR or AR continues to evolve toward early surgical intervention,[1] it is important that early preemptive surgery be performed only in those with truly severe regurgitation. Similarly, surgery in symptomatic patients is recommended only when AR or MR is considered severe enough to be the cause of symptoms. Thus, quantifying severity of regurgitation with echocardiography or CMR is of paramount importance in determining whether asymptomatic or symptomatic patients are candidates for surgical or percutaneous intervention. In such cases, however, patient symptoms and all of the skills of the clinician such as meticulous physical examination and history taking are of equal importance to the results of the imaging itself to identify those with truly severe disease.

In patients with secondary TR associated with MV disease, surgical repair of severe TR is indicated at the time of MV surgery whether or not there are clinical signs of severe TR. In such situations, the decision for concomitant TV repair is driven principally by imaging evidence of severe TR or severe dilation of the tricuspid annulus.[1] In contrast, in patients with primary TR, the clinical presentation is also of great importance, as the indications for surgical tricuspid repair or replacement are strongest in those with symptoms, declining exercise tolerance, or evidence of RV failure. However, TV surgery may also be considered in asymptomatic patients when there is evidence of severe TR associated with progressive RV dilation or systolic dysfunction. Diagnosing the etiology of primary TR is often challenging. Expert imaging with echocardiography or CMR is the key to reduce misdiagnoses.

Isolated PR in adults is usually innocuous and rarely severe. A high-pitched murmur of PR, however, may be an important clinical marker of primary or secondary pulmonary hypertension. In addition, PR following repair of tetralogy of Fallot is a common late complication of previous surgical repair with important clinical implications. Patients with previous tetralogy repair should be considered for surgery if severe PR is present in the setting of symptoms, declining effort tolerance, RV dilation/dysfunction, atrial or ventricular arrhythmias, or moderate to severe TR.[271] As the murmur of PR may itself be unimpressive, awareness of the high frequency of this late complication following otherwise successful repair, with appropriate referral for imaging, is essential. Similarly, hemodynamically important PR in the absence of pulmonary hypertension is a possible late outcome in patients who have undergone transcatheter or surgical PV repair or replacement for pulmonic stenosis and in patients with a pulmonary homograft following a Ross procedure. This emphasizes the need for long-term follow-up of such patients.

In asymptomatic patients with known valvular disease who are being followed serially, the timing of imaging studies changes when there are changes in the clinical situation. Exercise stress testing is used to assess functional capacity and equivocal symptoms. The onset of possible or definite symptoms or changes in the timing or intensity of the murmur should trigger repeat echocardiography or CMR. In patients with bicuspid aortic valves, a new murmur of AR could reflect an increase in severity or dilatation of the aortic sinuses or ascending aorta and is an indication for comprehensive imaging with echocardiography, CMR or both.


  Future Directions Top


Cardiovascular imaging has had a major impact in the diagnosis, prognosis, and management of patients with valvular heart disease. In general, regurgitation may present a challenge for most diagnostic techniques because of the dynamic nature of the lesion and its dependence on various hemodynamic and physiologic conditions. For all valvular regurgitation, irrespective of the modality, an integrative approach is recommended to achieve an accurate evaluation of the severity of the lesion and its clinical significance. This takes into account physiologic conditions that could alter the accuracy of certain parameters, emphasizes the quality of the primary data, and allows internal verification of the interpretation. Future developments should aim for advances in ultrasound and CMR techniques, more automation in quantitation to reduce variability, and more data on quantitation and grading of right heart lesions in relation to outcomes. In real-time 3D imaging, improvements in temporal and spatial resolution to enhance display of valve regurgitation and improve automation of flow convergence, VC, and the regurgitant jet would be welcome. Recent advances have included the use of 3D volume color Doppler acquisition followed by use of the velocity information intrinsic to color Doppler data to quantify SVand PISA in mitral,[67],[272],[273],[274] aortic,[275] and TR.[243] The important potential strengths of these methods include the increased reproducibility of quantification, reduced dependency on shape and size assumptions, and improvement in work flow, allowing easier integration into routine clinical practice. In CMR, further improvements in quantitation of flow across mitral and TVs, taking into account annular motion, would further enhance the power of the technique to quantitate individual and multiple valve lesions.


  Reviewers Top


This document was reviewed by members of the 2016-2017 ASE Guidelines and Standards Committee, ASE Board of Directors, ASE Executive Committee, and a representative for the Society for Cardiovascular Magnetic Resonance.

Reviewers included Deborah A. Agler, RCT, RDCS, FASE, Federico M. Asch, MD, FASE, Merri L. Bremer, EdD, RN, EDCS, ACS, FASE, Benjamin Byrd, MD, FASE, Hollie D. Carron, RDCS, FASE, Joao L. Cavalcante, MD, FASE, Scott D. Choyce, RDCS, RVT, RDMS, FASE, Frederick C. Cobey, MD, FASE, Meryl Cohen, MD, FASE, Patrick H. Collier, MD, PhD, FASE, Keith A. Collins, MS, RDCS, FASE, Mary C. Corretti, MD, FASE, Benjamin Eidem, MD, FASE, Mark K. Friedberg, MD, FASE, Neal Gerstein, MD, FASE, Edward A. Gill, MD, FASE, Yvonne E. Gilliland, MD, FASE, Robi Goswami, MD, FASE, Stephen Heitner, MD, FASE, Lanqi Hua, RDCS, FASE, Soo H. Kim, MD, MPH, RPVI, FASE, James N. Kirkpatrick, MD, FASE, Allan L. Klein, MD, FASE, Jonathan R. Lindner, MD, FASE, Rick Meece, ACS, RDCS, RCIS, FASE, Carol Mitchell, PhD, RDMS, RDCS, RVT, RT (R), ACS, FASE, Tasneem Naqvi, MD, FASE, Maryellen H. Orsinelli, RN, RDCS, FASE, Andy Pellett, PhD, RCS, RDCS, FASE, Patricia A. Pellikka, MD, FASE, Sue D. Phillip, RCS, FASE, Juan Carlos Plana, MD, FASE, Vera H. Rigolin, MD, FASE, Vandana Sachdev, MD, FASE, Anita Sadeghpour, MD, FASE, Liza Y. Sanchez, RCS, FASE, Elaine Shea, ACS, RCS, RCCS, FASE, Roman M. Sniecinski, MD, FASE, Raymond F. Stainback, MD, FASE, Cynthia Taub, MD, FASE, Seth Uretsky, MD, Steven Walling, RCS, RDCS, FASE, Neil J. Weissman, MD, FASE, Susan E. Wiegers, MD, FASE, and David H. Wiener, MD, FASE.


  Notice and Disclaimer Top


This report is made available by ASE as a courtesy reference source for members. This report contains recommendations only and should not be used as the sole basis to make medical practice decisions or for disciplinary action against any employee. The statements and recommendations contained in this report are primarily based on the opinions of experts, rather than on scientifically verified data. ASE makes no express or implied warranties regarding the completeness or accuracy of the information in this report, including the warranty of merchantability or fitness for a particular purpose. In no event shall ASE be liable to you, your patients, or any other third parties for any decision made or action taken by you or such other parties in reliance on this information. Nor does your use of this information constitute the offering of medical advice by ASE or create any physician-patient relationship between ASE and your patients or anyone else.

The following authors reported relationships with one or more commercial interests: Maurice Enriquez-Sarano, MD, received research support from Edwards LLC; Elyse Foster, MD, FASE, received grant support from Abbott Vascular Structural Heart and consulted for Gilead; Paul A. Grayburn, MD, FASE, consulted for Abbott Vascular, Neochord, and Tendyne and received research support from Abbott Vascular, Tendyne, Valtech, Edwards, Medtronic, Neochord, and Boston Scientific; Rebecca T. Hahn, MD, FASE, is a speaker for Philips Healthcare, St. Jude's Medical, and Boston Scientific; Yuchi Han, MD, MMSc, received research support from Gilead and GE; Roberto M. Lang, MD, FASE, is on the advisory board of and received grant support from Phillips Medical Systems; Dipan Shah, MD, MMSc, received research grant support from Abbott Vascular and Guerbet; Stanton Shernan, MD, FASE, is an educator for Philips Healthcare, Inc.; James D. Thomas, MD, FASE, received honoraria from Edwards and GE, and honoraria, research grant, and consultation fee from Abbott; and William A. Zoghbi, MD, FASE, has a licensing agreement with GE Healthcare and is on the advisory board for Abbott Vascular.

Conflicts of interest

The following authors reported no actual or potential conflicts of interest in relation to this document: David Adams, RCS, RDCS, FASE; Robert O. Bonow, MD; Judy Hung, MD, FASE; Stephen H. Little, MD, FASE; Paaladinesh Thavendiranathan, MD, MSc; and Neil J. Weissman, MD, FASE



 
  References Top

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Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2438-88.  Back to cited text no. 1
    
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Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD, Levine RA, et al. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003;16:777-802.  Back to cited text no. 2
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16], [Figure 17], [Figure 18], [Figure 19], [Figure 20], [Figure 21], [Figure 22], [Figure 23], [Figure 24], [Figure 25], [Figure 26], [Figure 27], [Figure 28], [Figure 29], [Figure 30], [Figure 31], [Figure 32], [Figure 33], [Figure 34], [Figure 35]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12], [Table 13], [Table 14], [Table 15], [Table 16], [Table 17]



 

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Table of Contents
Introduction
Evaluation of Va...
Mitral Regurgitation
Aortic Regurgitation
Tricuspid Regurg...
Pulmonary Regurg...
Considerations i...
Integrating Imag...
Future Directions
Reviewers
Notice and Discl...
References
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