review can ventricular function be assessed by

REVIEW

12 Journal of Small Animal Practice • Vol 50 (Suppl. 1) • September 2009 • © 2009 British Small Animal Veterinary Association

Can ventricular function be assessed by echocardiography in chronic canine mitral valve disease?

INTRODUCTION

Mitral regurgitation (MR) in dogs is most often caused by chronic degenerative val-vular disease (CDVD). This lesion, also called valvular endocardiosis and myxo-matous valvular disease, develops slowly and increases in severity over a period of years (Pedersen and Häggström 2000, Häggström and others 2004). Progres-sive MR induces cardiac remodelling, characterised by left atrial (LA) and left

ventricular (LV) dilatation, eccentric myocardial hypertrophy and alteration of the intercellular matrix. Neurohormonal activation and the narrowing of small (intramural) coronary arteries may play roles in the pathogenesis of LV remodel-ling (Killingsworth and others 2008). De-spite preservation of global LV shortening, LV dysfunction can eventually develop in CDVD (McGinley and others 2007), along with increases in LA and pulmonary venous and pulmonary arterial pressures. By this stage, many dogs are symptomatic for heart failure.

Echocardiography (Echo) can identify and track many of these developments non-invasively (Serres and others 2007a), and offers useful information about the heart and circulation in chronic MR. This brief review, directed to the veterinary surgeon in small animal practice, focuses on developments in echocardiographic as-sessment of LV function and ventricular fi lling in dogs with CDVD.

PRINCIPLES

A comprehensive clinical approach to assessing the severity of MR is optimal. This should consider the historical, physi-cal, blood pressure, radiographic, electro-cardiogram (ECG) and clinical laboratory fi ndings along with changes evident by integrated two-dimensional (2D), M-mode and Doppler echocardiographic studies. Echocardiographic abnormalities of importance include understanding the nature of the valvular lesion, severity of MR, degree of cardiac remodelling, pres-ence of systolic and diastolic ventricu-lar dysfunction and fi ndings indicating elevations of intravascular pressures (Ma-zur and Nagueh 2001, O’Gara and others 2008) (Table 1).

An example of this integrated Echo approach can be given. A chordal rupture creating a fl ail leafl et and wide-origin jet of MR that extends into the pulmonary veins would signal severe MR. Similarly, evi-dence of moderate-to-severe cardiomegaly

Mitral regurgitation (MR) related to chronic degenerative valvular

disease is the most important cause of heart failure in dogs.

Ultrasound examination of the heart can identify valve lesions,

confi rm the presence of valvular regurgitation, document cardiac

remodeling, estimate intracardiac pressures, and quantify systolic

ventricular function. These fi ndings can infl uence prognosis or

selection of medical therapy. Reductions in ventricular systolic

function may be detected on serial echocardiographic examinations

in some dogs with MR. However the changes in ventricular loading

that accompany MR often complicate these measurements. For

example, shortening and ejection fractions are often increased

in severe MR, even in the setting of congestive heart failure.

Echocardiography with Doppler is also used to assess ventricular

diastolic function and fi lling pressures. This information helps

predict the risk of congestive heart failure. However these fi ndings

are often rendered ambiguous by age-related impairment of

ventricular relaxation, elevations in left atrial pressure due to MR,

and effects of volume overload on myocardial tissue velocities.

These factors limit the usefulness of ventricular fi lling and tissue

velocities, as well as derived ratios such as the E/E’ ratio, for

predicting congestive heart failure in MR. More advanced Doppler

and tissue echocardiographic methods, as well as prospective

clinical studies, are needed to reduce the ambiguity involved with

assessment of ventricular function and fi lling pressures in the

setting of MR.

J. D. BONAGURA AND K. E. SCHOBER

Journal of Small Animal Practice (2009) 50 (Suppl. 1), 12–24DOI: 10.1111/j.1748-5827.2009.00803.x

Accepted: 19 June 2009

Confl icts of Interest: JDB and KES declare no confl icts of interest.

Department of Veterinary Clinical Sciences, Ohio State University, Veterinary Medical Center, Columbus, OH 43210, USA

Ventricular function in chronic canine mitral valve disease

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Journal of Small Animal Practice • Vol 50 (Suppl. 1) • September 2009 • © 2009 British Small Animal Veterinary Association 13


with pulmonary arterial hypertension in-dicates chronic, severe mitral valve disease. Finally, identifi cation through Doppler echocardiography of high LA systolic and LV diastolic (fi lling) pressures would offer further evidence of clinically important

MR. One might logically assume that ventricular dysfunction would be evident in the aforementioned examples; however, the identifi cation of LV systolic or dia-stolic dysfunction in the setting of CDVD is actually quite challenging, and there

is no totally load independent measure available.

It might be asked whether such infor-mation even matters. We do know that in man the quantitation of LV function and ventricular fi lling pressures is pivotal

Table 1. Echocardiographic assessment of the dog with mitral regurgitation*

Cardiac rhythm

Account for effects of rhythm disturbances on echo variables

Impact of atrial fi brillation (when present)

Valve lesion

Thickening

Rupture of chordae tendineae

Motion abnormalities

Prolapse

Flail leafl et

Cardiac remodelling

Left atrial dilatation

Increased 2D or M-mode chamber diameter

Increased 2D or M-mode left atrial to aortic diameter

Increased left atrial to aortic diameter ratio

Dilated pulmonary venous entry

Rightward bowing of the atrial septum

Left ventricular dilatation

Increased end-diastolic diameter

Increased sphericity – apical rounding

Dilated LV chamber on short-axis image

Right heart lesions

Tricuspid valve thickening or prolapse

Enlargement of the right heart chambers

Pulmonary artery dilatation

Severity of mitral regurgitation

Colour Doppler methods

Receiving chamber analyses (jet length, width)

Proximal isovelocity area (PISA) to estimate regurgitant fl ow rate and regurgitant volume

Width of the MR vena contracta (jet)

Pulsed and continuous-wave Doppler methods

Strength of regurgitant signal (using “standard” transducer and gain settings)

Duration of the regurgitant MR jet

Regurgitation into the pulmonary veins (systolic fl ow reversal)

Magnitude of peak MR velocity (measuring LV to LA pressure gradient)

Contour of the MR jet (rounded versus pointed)

Volumetric estimates of regurgitant volume (total LV stroke volume – forward stroke volume)

Calculation of effective regurgitant orifi ce (indexed to body surface area)

Pulmonary artery pressure

Elevated tricuspid regurgitant jet velocity (indicating pulmonary hypertension)

Elevated pulmonary regurgitant jet velocity (indicating pulmonary hypertension)

Left ventricular systolic function (Table 2)

Evidence for impaired global or regional LV function

Ventricular diastolic function (Table 2)

Evidence for age-related relaxation abnormality or reduced LV chamber compliance

Ventricular fi lling pressures (Table 2)

Evidence for increased left atrial (and pulmonary venous) pressures

MR mitral regurgitation, LV left ventricle/ventricular, E early diastolic LV fi lling wave, A late diastolic LV fi lling wave (atrial contraction).*This list is not comprehensive.


J. D. Bonagura & K. E.Schober


because the information guides surgical intervention. However, surgical treatment of canine CDVD is rarely undertaken, so this consideration is largely irrelevant. However, information about LV function in CDVD might help us to better under-stand the natural history of this disease, offer more accurate prognoses and guide follow-up care. Potentially, the medical therapy for affected dogs could be infl u-enced by an echocardiographic assess-ment of LV function or elevated fi lling pressures. For example, documentation of elevated LA and pulmonary venous pres-sures would likely prompt treatment to prevent congestive heart failure (CHF), or at the least, a need for frequent follow-ups or thoracic radiographs. Specifi cally how such data should be used clinically requires more defi nition. The authors’ personal perspectives are offered at the conclusion of this review.

The traditional measures of global LV systolic function are the ejection and shortening fractions (Table 2). Ejection fraction (EF) is commonly measured by 2D Echo using a single-plane (long axis or apical) image of the LV. Shortening frac-tion (SF) is measured in most situations from the M-mode echocardiogram but also can be determined from a frozen 2D image (Figs 1 and 2). In addition, experi-enced examiners may subjectively evaluate radial shortening of the LV (that is, from diastole to systole) in the short-axis plane at the level of the papillary muscles. Systol-ic heart failure is classically characterised by reduced EF and SF and subjectively by reduced radial shortening (fractional area shortening); however, in CDVD these measures can be very misleading (Lee and Marwick 2007). Signifi cant MR increases LV preload and reduces afterload. These alterations foster a normal to hyperdy-

namic ventricular contraction, even in the presence of impaired myocardial cell contraction.

Global LV contraction depends on myocardial contractile function (inotropy) and the loading conditions (Higgins and others 1973). Ventricular volume (pre-load) is increased in MR due to volume retention, remodelling and elevations in LA and pulmonary venous pressures (Ka-tayama and others 1988). This augments global function by the Frank-Starling effect. Conversely, peak systolic wall stress (a measure of the afterload opposing shortening) is reduced, at least until end-stage MR has set in (O’Gara and others 2008). This is explained by the retrograde LV stroke volume that is ejected into the LA even before ejection into the aorta. There is no isovolumetric contraction period, because the mitral valve leaks as soon as ventricular pressure begins to rise.

Table 2. Echocardiographic assessment of left ventricular function and fi lling pressures in the dog with mitral regurgitation*

Impaired left ventricular systolic function

Normal-to-reduced ejection fraction† in setting of moderate-to-severe MR

Normal-to-reduced shortening fraction‡ or fractional shortening area in setting of moderate-to-severe MR

Increased end-systolic volume or end-systolic diameter index

Reduced left ventricular free-wall excursion

Reduced left ventricular wall thickening

Decreased global or regional myocardial strain

Decreased global or regional myocardial strain rate

Impaired diastolic function

Reduced E/A wave ratio of transmitral fl ow (relaxation abnormality)

Reduced E’ velocity and E’/A’ ratio in tissue Doppler echo (relaxation abnormality)

Normal E’ velocity in the setting of high LV preload

Decreased diastolic strain rate

Restrictive fi lling pattern of large E/A wave ratio of transmitral fl ow (reduced LV distensibility)

Increased fi lling pressures

Increased end-diastolic ventricular volume or diameter§

Pseudonormal fi lling pattern (normal E/A wave ratio) in a dog with previously recognised relaxation abnormality or dog > 10 years of age

Increased velocity of the early fi lling (E) wave of transmitral fl ow

Increased ratio of the E-wave/E’ in the tissue Doppler

Shortened deceleration time of the E-wave of transmitral fl ow

Shortened isovolumetric relaxation time

Increased ratio of mitral E-wave/isovolumetric relaxation time

MR mitral regurgitation, LV left ventricle/ventricular, E early diastolic LV fi lling wave of transmitral fl ow, A late diastolic LV fi lling wave (atrial contraction) of transmitral fl ow, E’ and A’ = early (E’) and late (A’) diastolic recoil recorded from the dorsal LV wall and dorsal ventricular septum as measured by tissue Doppler Echocardiography.*This list is not comprehensive.†Ejection fraction = (End-diastolic Volume – End-systolic Volume) End-diastolic VolumeLV volumes are calculated from single plane, long-axis 2D image (Fig. 1) (0·85) LVarea2 Length An alternative single or biplane approach uses the method of discs (Simpson’s rule) to estimate LV volumes.‡Shortening fraction = (End-diastolic dimension – End-systolic dimension) End-diastolic dimensionDimensions are measured from the M-mode echocardiogram (Fig. 2).For fractional area shortening, the traced short-axis areas are substituted for the linear dimensions.§Typically identifi ed in dogs with elevated fi lling pressures but other fi ndings are needed to confi rm the diagnosis.




Consequently, ventricular volume at ejec-tion can be substantially less than the maximal diastolic (fi lling) volume, and this reduces peak wall tension (afterload) at the onset of aortic valve opening. The LA continues to provide a path of lower resistance for ejection until ventricular pressure falls below LA pressure during ac-tive relaxation and ventricular untwisting. Combined, these conditions often cre-ate an image of a dilated, hyperdynamic chamber when viewed by traditional 2D

and M-mode Echo (Figs 2 and 3). Con-sequently, it is diffi cult to identify LV systolic dysfunction until it is relatively advanced.

The assessment of LV diastolic func-tion is possibly more diffi cult in the dog with MR. Diastolic function is compli-cated with critical components including active myocardial relaxation, untwisting, chamber stiffness (compliance or disten-sibility), and the instantaneous LA to LV pressure gradient driving blood across the

opened mitral valve (Nagueh and others 2009). The LA pressure directly relates to regurgitant volume, LA compliance and pulmonary venous pressure. Dogs with CDVD are typically older, and LV relax-ation can be impaired as a function of age or associated conditions such as systemic hypertension. With severe volume over-load, higher LV operating chamber stiff-ness can develop reducing distensibility so that LV fi lling proceeds under higher than normal atrial pressures. If cardiac output becomes limited during exercise, compensatory mechanisms such as renal sodium retention and renin-angioten-sin-aldosterone activation may augment venous pressures. In addition, moderate-to-severe MR produces an abrupt increase in LA pressure related to the simultane-ous arrival of the regurgitant stroke vol-ume and pulmonary venous return. This prominent positive waveform (v-wave) transiently increases LA pressure, and contributes somewhat disproportionately to early LV fi lling, a period often used to assess diastolic function. Thus, the Echo assessment of diastolic ventricular func-tion in heart failure becomes a combined assessment refl ecting the interplay of muscle relaxation, untwisting, chamber compliance (or distensibility), regurgitant volume, atrial function and venous pres-sures (Ohno and others 2004). The spe-cifi c Echo assessment involves a number of variables derived from routine imaging, Doppler studies and specialised evalua-tions of the cardiac tissues. Even with a full complement of Echo data, the diastol-ic assessment can be ambiguous.

Currently, the Echo evaluation of LV function and fi lling pressures in dogs with CDVD is based on surrogate mea-sures that relate to ventricular remod-elling, pumping function and fi lling (Table 2). In the future, the application of stress or exercise Echo may be useful for identifying contractile reserve (or its absence). Echo evaluations used by the authors’ and by others are considered in the following sections that are devoted to 2D and M-mode Echo studies, Doppler examinations and advanced tissue-based studies of LV function. A multi-modal-ity approach for assessment of systolic LV function in MR is suggested, along with consideration of serial examinations

FIG 1. Long-axis image of the heart from the right thorax obtained at end-diastole from a large-breed dog with mild mitral regurgitation and normal cardiac chamber sizes. A method for tracing the internal area of the left ventricle (LV) and length (L) is shown. From these two measurements, LV volume can be calculated. Diastolic and systolic volumes are needed to estimate ejection fraction. The diameter D is the minor dimension that is typically measured by M-mode echocar-diography. LA left atrium, LV left ventricle, LVW left ventricular free wall, RA right atrium, RV right ventricle. One cm calibration marks are shown

FIG 2. Short-axis image of the left ventricle (left) and M-mode echocardiogram (right) obtained with the transducer on the right thorax from a small-breed dog with mild-to-moderate mitral regurgi-tation (MR). The M-mode cursor bisects the 2D image of the left ventricle. The resultant M-mode image demonstrates the method for measuring the LV in diastole (D) and systole (S). Shortening fraction is calculated as (D–S)/D and is normal to hyperdynamic in this case. IVS intact ventricular septum, LVW left ventricular free wall, RV right ventricle. One cm calibration marks are shown; sweep speed is 100 mm/s




for identifi cation of progressive LV dys-function. Principles identifying diastolic dysfunction and elevated fi lling pressures – heralding a dog at current risk for CHF – are advanced. Finally, some personal recommendations are offered about the practical use of these measured and calcu-lated parameters.

TWO-DIMENSIONAL AND M-MODE ECHOCARDIOGRA-PHY IN CHRONIC VALVULAR DISEASE

The LV volumes and diameters need-ed for calculation of EF and SF can be estimated from 2D or M-mode echocar-diographic images (Figs 1 to 3). The EF calculation informs us about the percent of blood ejected from the LV during sys-tole. In MR, more than half of the total stroke volume may be ejected retrograde (into the LA), so that LV volume changes over the cardiac cycle are not equivalent to cardiac output. Volumes are calculated with 2D Echo from an area tracing of the internal LV area using a single long-axis plane or two right-angled (orthogonal)

apical image planes. Area is usually calcu-lated from a length-area method (which assumes the LV is an ellipsoid chamber) or from a Simpson’s rule method (of summed discs). The specifi c method is controlled by software settings of the echocardio-graphic system. Normal values for EF in healthy dogs using single-plane methods are approximately 45 to 55 per cent in our laboratory. Volume estimates from the M-mode Echo are generally made by cubing the minor dimension and adjust-ing for changes from normal geometry (Serres and others 2008). The Teicholz adjustment is used in most Echo systems, but this M-mode approach often results in inaccurate volumetric estimates.

The SF is a linear estimate of EF, repre-senting the percentage change of a single minor LV dimension from diastole to sys-tole. The SF is generally measured from an M-mode Echo. SF is calculated by dividing the change in LV diameter over the cardiac cycle by the initial (end-diastolic) dimen-sion (Table 2). Normal values for SF are approximately 30 to 40 per cent for small-breed dogs but probably as low as 22 to 25 per cent in larger breed dogs. The exam-iner can also evaluate the movements of

multiple short-axis dimensions by tracing the internal LV area to calculate fractional area shortening at the dorsal papillary level. This value approximates the EF, and in our laboratory exceeds 45 per cent in most healthy dogs. The actual percent of ventricular shortening identifi ed using any of these methods relates to technical aspects of recording and measurement; physiological state; body size; and im-portantly the volume of MR as described below.

Each of these systolic function indices is unreliable in the setting of moderate-to-severe MR due to CDVD. In these situations, both EF and SF achieve values exceeding normal and the shortening area appears hyperdynamic when observed in real time. Cardiologists often remark that a dog with severe MR and preserved LV function should have a hyperdynamic chamber, but it is diffi cult to quantify how high that value should achieve in a given case. Values for SF are often in the 45 to 55 per cent range, even in dogs with overt CHF (Borgarelli and others 2007). The corresponding values for EF often exceed 70 per cent. For this reason, fi nding a nor-mal EF or SF in the presence of advanced

FIG 3. Angled long-axis images from the right thorax recorded in diastole (left) and systole (right). Note the hyperdynamic contraction of the myocar-dial walls and reduced area of the ventricular cavity (left arrows) along with marked increase in left atrial (LA) size developing between diastole and systole. These fi ndings are related to altered ventricular loading conditions and ejection of much of the left ventricular (LV) stroke volume into the LA. The mitral valve orifi ce is shown by small arrows (right panel); S ventricular septum; W left ventricular wall; PM caudal (posterior) papillary muscle. One cm calibration marks are shown on the left




MR suggests signifi cant LV myocardial failure, and perhaps a poorer prognosis. Downward trends exceeding 5 to 8 per cent in a dog with progressive volume overload identify reduced systolic func-tion, assuming consistent examination conditions and heart rate. The situation is slightly different in larger breed dogs wherein normal-to-low SF is more com-monly encountered in the setting of ad-vanced CDVD (Fig 4) (Borgarelli and others 2004, Häggström 2004).

Linear minor axis dimensions of the LV obtained from the M-mode study are also instructive. First, as MR worsens over time, LV diastolic volume, as estimated by the in-ternal (minor) diameter, increases in value (Fig 3). Certainly, it would be surprising to identify a normal LV diastolic dimen-sion in a dog with advanced mitral valve disease. This fi nding of increased diastolic dimension is compatible with ventricular dilatation and volume overload. Secondly, as systolic function becomes impaired, the end-systolic dimension increases, despite the escalating volumes ejected into the lower resistance LA (O’Gara and others 2008). Thirdly, if LV contractile function is preserved, the fully compensated ventri-cle will shorten to the almost normal end-systolic volume (or diameter). Kittleson and others (1984) advanced this concept in small-breed dogs with MR, suggesting

that an increased end-systolic volume in-dex (the dimension relative to body mass) correlated to impaired LV systolic function. They estimated LV end-systolic volumes in dogs based on the M-mode echocar-diogram, using 30 ml/m2 as the suggested upper limit of normal. In a study by Bor-garelli and others (2007), the end-systolic volume index was also abnormal in dogs with CHF caused by CDVD. In large-breed dogs with chronic MR due to val-vular disease there can be such a marked increase in end-systolic diameter that even EF and SF are grossly reduced (Fig 4).

The indexing or modelling of LV inter-nal measurements to body surface area or mass is very logical, and most studies show a general linear relationship between cham-ber size and body mass. However, multi-breed data sets suffer from relatively small sample sizes, gaps in data across body sizes and a relative lack of points at the extreme ends of very small and very large breeds (Cornell and others 2004). Accordingly, the 95 per cent confi dence limits that defi ne “normal” limits in most published studies, though statistically sound, are very wide. The end-systolic volume index depends on bodyweight as well and is smaller in small breeds than large-breed dogs. These factors limit the practical value of such data for identifying mild LV dilation and early LV systolic dysfunction. Thus, in the authors’

opinion, either breed-specifi c reference val-ues or consistently recorded, serial exami-nations from a canine patient are needed to identify the initial signs of LV dilatation and dysfunction using indexed methods. When LV dysfunction is moderate to vseverely reduced, multiple methods can be used to identify impaired systolic func-tion, including EF, SF and end-systolic di-ameter index.

Inspection of the LV free-wall on the M-mode Echo offers further information. A common feature of advanced CDVD in dogs is apparent reduction in regional LV wall motion relative to ventricular septal motion (Figs 4 and 5). In normal dogs, the amplitude of septal excursion is less than that of the free wall. This probably relates to both wall and global cardiac (transla-tional) movements and ventricular inter-dependence. However, in dogs with severe CDVD the opposite is often observed. This has been interpreted as regional LV systolic dysfunction, altered transla-tional motion from cardiomegaly, or per-haps both. However, experimentally this change has been related simply to altera-tions in LV geometry with deviation of the septum towards the right heart and greater leftward excursion of the septum during systole (Young and others 1996). Thus, the clinical relevance of this fi nding is un-resolved, other than supporting signifi cant

FIG 4. Two-dimensional (2-D) colour Doppler images from a larger breed dog with mitral valve disease obtained in early systole (before aortic ejection, left) and at end-systole (right). Notice that mitral regurgitation (MR) begins during the normally isovolumetric contraction period. Flow moving away from the transducer (blue) and towards the transducer (red) converge into a jet (arrowheads) within the mitral orifi ce. The green colour encoding turbu-lence continues far into the left atrium (LA) and pulmonary veins. When compared with Fig 3 the severe LV systolic dysfunction in this case with poor wall thickening and a low shortening fraction, is very apparent. There is some “colour bleeding” across the grey scale walls in the right panel. LVSF left ventricular shortening fraction. One cm calibration marks are shown at the left of each panel, along with the minor dimensions measured for each image




into the 5 to 6 m/s range, provided par-allel alignment to fl ow is obtained dur-ing the examination. In cases of systemic hypertension (or LV outfl ow obstruc-tion), the peak regurgitant velocity may exceed 6·5 m/s owing to elevated LV sys-tolic pressure. Conversely, when there is severe systolic dysfunction, systemic hy-potension, volume depletion secondary to excessive diuresis, or when pressures in the LA are very high, both the peak velocity and the rate of velocity change may be reduced. These changes refl ect re-ductions in maximal instantaneous pres-sure gradient and diminished vigour of LV contraction. The subjective contour of the MR jet may also change from a rounded peak to a more abrupt peak with a rapid velocity deceleration if there is an abrupt and severe increase in LA pressure associated with MR.

Another application of the simplifi ed Bernoulli equation is calculation of the fi rst derivative of LV pressure change, dp/dt, from the MR jet. This index is an es-timate of global LV systolic function and it can decline in advanced MR. Canine studies have demonstrated a close rela-tionship between catheter-measured and Doppler-estimated dp/dt (Chen and oth-ers 1991, Asano and others 2002). One simple method for calculating this variable is shown in Fig 6B, and involves measuring the time period between the 1 and 3 m/s time points along the MR spectrum. Ref-erence values for dp/dt using this method in small-breed dogs with mild MR and normal LV function have not been pub-lished, but in our experience, these values are lower than those of instantaneous dp/dt recorded from instrumented dogs; these often exceed 3000 mmHg/s (Higgins and others 1973). As with other LV func-tion indices, downward trends will be more instructive than one single measurement.

Many dogs with CDVD also develop tricuspid regurgitation related to degener-ative valve changes (prolapse, thickening) and pulmonary hypertension (PH), which is a consequence of chronic, moderate-to-severe MR. In some dogs, PH is severe, can lead to clinical signs such as exertional col-lapse or right heart failure, and creates an indication for pharmacologic management (see later). Pulmonary hypertension can be explained fi rst by the increase in peak and

FIG 5. M-mode echocardiogram at the LV level from a small-breed dog with severe mitral regurgita-tion (MR) due to chronic valvular disease. The overall LV shortening fraction is hyperdynamic but the ventricular septum (IVS) has greater excursion than the left ventricular free wall (LVW). The excursion or amplitude of the ventricular septum (amp-S) to its nadir is shown; compare this with the amplitude of the left ventricular free wall (amp-W). The onset of the QRS and the nadir of the septum are marked with vertical lines. The diastolic (D) and systolic (S) measurements are shown. One cm calibration marks are shown at the left

regions of interest. Advanced tissue meth-ods are often based on colour M-mode studies. Doppler studies are used to iden-tify and quantify MR, assess ventricular function and estimate LV fi lling pressures (Tables 1 and 2). The assessment of MR severity by Doppler Echo is a separate top-ic (Uehara and Takahashi 1996, Kittleson and Brown 2003, Choi and others 2004, Gouni and others 2007), but it stands to reason that LV dysfunction and elevated LA pressures in CDVD are predicated on Doppler fi ndings of severe MR.

Continuous-wave Doppler studies of MR can be used to identify elevated LA pressures and LV systolic and diastolic dysfunction. Mitral regurgitation is char-acterised by high velocity, turbulent, sys-tolic jets recorded at the valve orifi ce and within the left atrium. The red blood cell (RBC) velocity at the envelope of the jet (Fig 6A) depends on the instantaneous pressure difference or gradient (Chen and others 1991). This gradient is relat-ed to the simplifi ed Bernoulli equation (LV – LA Pressure = 4V2, with velocity in m/s). The peak CW velocity of MR in most normotensive dogs should fall

volume overload of the LV. Regional wall abnormalities also may be evident with advanced echocardiographic imaging such as myocardial strain. In addition, one can measure the LV wall thickness along with diastolic LV dimension to estimate LV mass. It has been reported that insuffi cient hypertrophy, as assessed by the wall thick-ness to chamber radius ratio, may be a risk factor for development of ventricular dys-function and heart failure in larger breed dogs with CDVD (Borgarelli and others 2007).

DOPPLER ECHOCARDIO-GRAPHIC STUDIES IN CHRONIC VALVULAR DISEASE

Doppler Echo studies measure direction and velocity of either blood fl ow or tis-sue targets and include the modalities of colour 2D and M-mode imaging, spectral Doppler imaging [pulsed wave and con-tinuous wave (CW)] and tissue Doppler imaging. The latter can be conducted us-ing a specialised pulsed-wave system or using postprocessed computer analysis of




mean LA pressures that occur with chronic MR (Chiavegato and others 2009). Other pathophysiological mechanisms, including pulmonary arteriopathy from high LA pres-sure or intercurrent lung disease are prob-ably important, but are largely unstudied in dogs. The tricuspid regurgitant velocity is directly related to peak pulmonary artery systolic pressure, and normally peaks at less than 2·6 m/s (unless there is elevated right ventricular systolic pressure). Although the precise tricuspid regurgitant velocity defi n-ing PH in dogs is not established, velocities exceeding more than 3 m/s (in the absence of right ventricular outfl ow obstruction) generally indicate elevated pulmonary ar-tery pressures (Schober and Baade 2006, Serres and others 2007b). Other methods for identifying PH, such as the ratio of PA acceleration time to ejection time can be useful when tricuspid regurgitation is not evident. This ratio decreases as pulmonary artery resistance increases because outfl ow velocity is achieved earlier during the ejec-tion period. In a study of West Highland White terriers with pulmonary fi brosis, a ratio of less than 0·31 was 87 per cent specifi c for the diagnosis of PH (Schober and Baade 2006). In another study of dogs with PH due mainly to MR, acceleration time/ejection time ratio averaged 0·46 in the controls but was reduced (to a mean of 0·37) in dogs with moderate-to-severe PH (Serres and others 2007b). Following this ratio in dogs with progressive MR may be useful in identifying onset of signifi cant PH and in evaluating its treatment.

Doppler recordings of transmitral fl ow velocity and the diastolic movements of the ventricular wall and septum can be quantifi ed to identify diastolic dysfunc-tion and elevated LV fi lling pressures (Fig 7). These variables are inter-related. The early (E) wave of transmitral fl ow in cm/s can be measured by pulsed-wave or CW methods (Schober and Luis Fuentes 2001). Signifi cant MR is often associated with increased early diastolic fi lling veloci-ties related to high pressure regurgitant v-waves or elevated venous pressures. The combination of normal ventricular relax-ation and recoil along with normal fi lling pressures typically generate E-waves aver-aging about 0·6 to 0·8 m/s; normal atrial contraction produces an A-wave of 0·5 to 0·6 m/s or less, resulting in a normal E/A

FIG 6. (A) Continuous-wave (CW) Doppler recording of mitral regurgitation (MR) showing a relative-ly low peak velocity and “pointed” profi le. Assuming appropriate alignment to the jet, the low peak velocity (< 5m/s) indicates high left atrial (LA) pressure, systemic hypotension, or both. Diastolic fi lling waves are also shown (E and A) but these were not obtained with appropriate alignment. Although peak E velocity can be recorded by CW Doppler, the A-wave should be recorded with a pulsed-wave sample volume at the mitral tips. Velocity scale (m/s) is to the right; paper speed 100 mm/s. (B) Continuous-wave Doppler recording of MR showing a method for recording average LV dp/dt from the regurgitant jet. The 1 and 3 m/s time points were identifi ed. The pressure differ-ence between these two points is always assumed to be 32 mmHg (36 mmHg – 4 mmHg, based on simplifi ed Bernoulli equation). The time interval between these was 44 ms. 32 mmHg/44 ms = dp/dt of 727 mmHg/s, which is a very low value for dp/dt. Most normal dogs are greater than 1800 mmHg/s using this method. Velocity scale (m/s) is to the right; paper speed 200 mm/s

(a)

(b)




wave ratio exceeding 1·0 (Bonagura and others 1998). The E/A ratio can decline even with normal aging (Schober and Luis Fuentes 2001) and with causes of LV hypertrophy. There are parallel, though lower velocity, diastolic movements ob-served in the LV myocardium using tis-sue Doppler imaging. These movements are represented by the E’ and A’ velocity waveforms (Fig 7). Mild diastolic dysfunc-tion is characterised by impaired myocar-dial relaxation. This condition reduces the amplitude of the transmitral E-wave and shifts more of ventricular fi lling to later in diastole (creating an E/A ratio of <1·0). The early diastolic recoil (E’) in the ventricular walls is similarly reduced

so that E’/A’ ratio decreases to less than 1·0; Fig 7A (left) and B. An increasing LA pressure caused by MR can normalise the transmitral fl ow pattern (pseudonormal fi lling), reproducing a normal E/A ratio. However, a similar change does not usu-ally occur in the tissue Doppler pattern.

This concept that increased LA pres-sure will normalise early fi lling veloc-ity (transmitral E-wave velocity), but that tissue velocities (E’) will be minimally affected, constitutes the basis for using the ratio of E/E’ as an estimate of LV fi ll-ing pressures (Nagueh and others 1997, Lisauskas and others 2001). Essentially, the E’ of the tissue “corrects” for the effects of relaxation on transmitral E-wave velocity,

so that a high ratio is suggestive of CHF(Nagueh and others 1997, Nagueh and others 2009). However, it is critical to understand that using E/E’ for prediction of fi lling pressures is only valid when E’ is reduced and relatively independent of the effects of preload. Unfortunately, in advanced MR, there is considerable vol-ume overload and if diastolic function is not impaired the ratio of E/E’ may be a poor predictor of LV fi lling pressures (Jacques and others 2004, Schober and others 2008a, 2008b). This preload infl u-ence probably explains why the prediction of the high fi lling pressures characteristic of CHF is far more diffi cult in MR, and why the proposed diagnostic ratios are

FIG 7. (A) Left: Pulsed-wave Doppler recording from an older dog showing a relaxation abnormality of transmitral fl ow. The E/A ratio is less than 1·0 and the slope of mitral deceleration (related to deceleration time) is prolonged. Centre panel: Continuous-wave Doppler recording of mitral regurgita-tion (MR) in a dog with severe MR showing a very high velocity E-wave greater than 1·5 m/s during early ventricular fi lling. Although optimally mea-sured by pulsed-wave Doppler, the slope of the mitral deceleration suggests impaired relaxation despite the normal E/A ratio (“pseudonormal” fi lling pattern). These fi ndings are compatible with elevated left atrial (LA) pressure and underlying diastolic dysfunction. Right: Transmitral fi lling recorded from a dog with MR showing a high E/A ratio and a steep slope compatible with a shortened deceleration time. This is compatible with elevated LA pressure and reduced left ventricular (LV) distensibility. Velocity scales (m/s) are to the right of each panel; paper speed 100 mm/s. (B) Tissue Doppler velocity recordings from a dog with MR from the dorsal ventricular septum (left) and lateral LV wall (right). There is E’/A’ reversal compatible with relaxation abnormality. The peak systolic velocities (S) are also somewhat reduced, which may indicate reduced regional systolic function. The isovolumetric contraction phase (upper arrow) and isovolumetric relaxation phase (lower arrow) are also evident. These represent rapid bidirectional shifts in tissue movements between the major waveforms. Velocity scales (m/s) is to the right; paper speed 100 mm/s

(a)

(b)




considerably higher than for patients with impaired LV systolic and diastolic function (for example, dilated cardiomyopathy).

Once the peak E-wave velocity exceeds 1·25 to 1·5 m/s, the likelihood of elevated fi lling pressures is much higher and the prognosis worse (Borgarelli and others 2008). In addition, a high E/E’ ratio may also predict elevated LA pressure, although this ratio seems inferior to other Doppler echo cardiographic variables in dogs with spontaneous CDVD. In one acute ex-perimental study, a ratio of E/E’ of greater than 9 was associated with a pulmonary wedge pressure of greater than 20 mmHg 95 per cent of the time (Oyama and oth-ers 2004). Data from our institution (KE Schober, JD Bonagura, V Samii and L Zekas 2009, unpublished observa-tions) suggest that an E/E’ ratio greater than 12, along with a high E-wave veloc-ity, can predict fi ndings of CHF on tho-racic radiographs in dogs with chronic spontaneous CDVD. This is similar to the ratio of 13 found to be about 80 per cent sensitive and specifi c for the di-agnosis of CHF in dogs (Teshima and others 2005). The precise cutoffs of E/E’ predicting heart failure are likely dif-ferent for acute versus chronic MR and require more study and clinical data.

Other Doppler measures such as pul-monary venous fl ow patterns are poten-tially useful, but often confusing due to projection of MR into the pulmonary veins. Another variable that has tracked LA pressure well in a number of studies in different species is the isovolumetric re-laxation time. This is the interval between the end of aortic ejection and the begin-ning of LV fi lling (and is obtained from combined mitral and aortic fl ow patterns). Normal isovolumetric time in healthy old-er dogs ranges from approximately 41 to 73 ms; impaired relaxation prolongs this interval while elevated LA pressure short-ens it (Schober and Luis Fuentes 2001, Schober and others 2008a,b). Although true isovolumetric relaxation does not oc-cur in MR, this time period is highly in-fl uenced by the combined effects of LV relaxation, LV compliance and LA pressure (Ohno and others 2004, Diwan and others 2005). The latter effect becomes the most prominent in dogs with advancing mitral valve disease. Progressive reduction in this

interval on serial examination is suggestive of elevated fi lling pressures and impaired LV diastolic function. This measurement is useful even in the setting of atrial fi brilla-tion (Nagueh and others 1996). In an acute study of volume loading, a ratio of peak E-wave velocity (in m/s) to isovolumetric re-laxation time (in ms) of more than 2·2 sug-gested mild-to-moderate elevations in LA pressure (>15 mmHg) (Schober and others 2008a). This ratio was also predictive of ele-vated fi lling pressures in another laboratory study (Schober and others 2008b). In our hospital, values of isovolumetric relaxation time of less than 45 ms and values of E:IVRT more than 2·5 in dogs with moder-ate-to-severe MR were often associated with radiographic signs of CHF in dogs with chronic MR (KE Schober, JD Bonagura, V Samii and L Zekas 2009, unpublished observations).

Another potentially useful variable is the mitral deceleration time [Fig 7A (right)], which can also be evaluated even in the setting of atrial fi brillation (provided short diastolic cycles are not chosen). The medi-an deceleration time in healthy older dogs is about 80 to 100 ms (Schober and Luis Fuentes 2001). A high velocity E-wave with an abbreviated deceleration time generally indicates the combination of a high LA pressure and a non- compliant LV (Giannuzzi and others 1994). However, in human beings this predictive ability is most obvious in situations of MR associ-ated with signifi cantly reduced LV systolic function (Temporelli and others 2001). In our studies of dogs with MR, mitral decel-eration time has been a weak predictor of elevated fi lling pressures.

ADVANCED METHODS FOR ASSESSING VENTRICULAR FUNCTION IN CHRONIC VALVULAR DISEASE

A number of tissue-centred and computer based methods have become popularised for assessing LV global and regional func-tion, and it is likely that some of these may be useful in dogs with CDVD. Aside from the tissue Doppler methods dis-cussed earlier, measurements of segmen-tal contraction velocity, deformation (or strain) and rate of deformation (strain

rate) (Gilman and others 2004) have been shown to be a sensitive indicators of ven-tricular function in some experimental canine studies (Wang and others 2007). The major promise of these examinations is found in the potential to identify LV dysfunction before simpler conventional methods are diagnostic. These variables are computer generated from proprietary software and both validation and repeat-ability studies are needed before these can be applied widely to veterinary situations. The strain data are derived from either tis-sue Doppler imaging or so-called “speckle tracking” of unique 2D grey scale images (Chetboul and others 2007). Myocardial function can be measured orthogonally in longitudinal, radial or circumferential orientations. Myocardial torsion or twist can also be calculated as tests of global systolic and diastolic function (Helle-Val-le and others 2005, Chetboul and others 2008). In models of canine MR, early diastolic twist becomes impaired indicat-ing diastolic dysfunction (Tibayan and others 2002).

An example of these advanced methods is shown in Fig 8. Peak myocardial defor-mation or strain occurs at the end of sys-tole and is used to assess systolic function only. The peak rate of change in strain (not shown) occurs in early systole and can also be measured in diastole. Strain rate relates to invasively measured LV func-tion in dogs. These correspond to peak systolic, early diastolic and atrial contrac-tion components of ventricular activity. The clinical application of these methods to dogs with MR requires more study be-fore these techniques can be recommend-ed for clinical decision-making.

POTENTIAL CLINICAL APPLICATIONS IN DOGS WITH CHRONIC DEGENERA-TIVE VALVE DISEASE

Aside from providing a detailed analysis of how the LV contracts and fi lls, the assess-ment of LV function and fi lling pressures by Echo will become really useful when these data assist with short- and long-term prognoses, guide follow-up intervals and help to direct cardiac therapy. Cer-tainly, the integrated Echo examination




contributes to the short-term prognosis and follow-up requirements in individual cases of CDVD characterised by either mild or very advanced cardiac remodel-ling. Whether or not ventricular function studies add information beyond that of simple size measurements is uncertain, but could be easily studied prospectively.

Some as yet unpublished data are emerging showing relationships between fi lling pressure estimates and radiographic signs of CHF. It may be reasonable in the future to perform directed Echo studies specifi cally to estimate the CHF risk in dogs with CDVD. Because radiography often requires a need for heavy sedation, this makes Echo estimates attractive, especially as availability of Echo systems

increases. How Doppler estimates of fi ll-ing pressures measure up against radiogra-phy and biomarkers such as NT-pBNP in dogs also needs more study. In our hospi-tal, Echo fi ndings suggesting high fi lling pressures usually prompt radiographic ex-amination for CHF, the introduction of an angiotensin-converting enzyme (ACE) inhibitor (+/– furosemide), more careful monitoring of respiratory rate at home and more frequent cardiac reevaluations. This is a practical outcome of including Dop-pler Echo variables into a multi- modality approach to monitoring dogs with MR. Any such approach must balance the pre-mature and inappropriate use of drugs of no proven value (at a particular stage of disease) versus the benefi t to both patient

and client of averting life-threatening CHF and an emergent presentation.

A similar approach is taken when the contour and peak velocity of the MR jet suggests severe left heart disease that is complicated by fi ndings of severe PH. The latter condition is recognised by a high velocity jet of tricuspid regurgitation, typically exceeding 4 m/s. Our general ap-proach to treating severe PH in the setting of advanced mitral disease involves fi rst re-ducing LA pressures by treating left heart failure with the combination of an ACE inhibitor, pimobendan, furosemide and spironolactone (Häggström and others 2008). When clinical signs are severe (exertional weakness, collapse or syncope, ascites), we generally initiate trial therapy

FIG 8. Segmental radial strain obtained from a dog with mitral regurgitation (MR) using a GE software system with 2-D grey scale, speckle track-ing algorithms. The upper left panel shows six arbitrary sectors in early systole before ejection. The lower left shows the colour coded peak radial strain (deformation) attained at end-systole. The percentage deformation (strain) is shown in the context of region of interest, time and percent deformation in the two graphs to the right. The colour coded changes show deformation proceeded synchronously, peaking near end-systole. The actual values are shown the upper right graph. The system also calculates a global circumferential strain from the data. The values appear normal in this dog




with the pulmonary vasodilator sildenafi l and amino acid l-arginine in the hope of reducing pulmonary vascular resistance and clinical signs. Such treatment requires prospective study, but it seems helpful in some canine patients. As a rule, we do not specifi cally treat for asymptomatic PH in dogs with MR.

When the MR jet velocity exceeds 6·5 m/s, systemic hypertension is likely to explain the high LV to LA pressure gradient. Hypertension increases the mi-tral regurgitant fraction. If non-invasive measurements of blood pressure confi rm the diagnosis, an ACE inhibitor is initi-ated to both lower blood pressure and treat the heart disease. However, most dogs with MR affected by moderate-to-severe systemic hypertension will require amlodipine or another dihydropyridine drug to reduce blood pressure to a tar-get systolic blood pressure of 100 to 120 mmHg.

The fi nding of systolic dysfunction in MR may also suggest the need for thera-py. In the authors’ view, it is unlikely that any systolic Echo variable will markedly alter treatment of dogs with established CHF, because these canine patients should already be receiving furosemide, an ACE inhibitor, pimobendan and spironolactone (Häggström and others 2008). However, in cases of MR with no signs of heart failure, but in which LV dysfunction is identifi ed by Echo, there may be a benefi t of cardioprotective ther-apies. These include beta-blockers such as carvedilol, atenolol or metoprolol and drugs that inhibit the renin-angiotensin-aldosterone system. Such therapy would require justifi cation by appropriate stud-ies, but in our own hospital, we do start large-breed dogs empirically on carve-dilol and enalapril (alternatives: benaz-epril or ramipril) when clear signs of LV systolic dysfunction or eccentric remod-eling are observed on multiple echo pa-rameters. There are no data supporting the administration of inotropic drugs such as pimobendan, levosimendan or digoxin to dogs with naturally occurring MR before the onset of CHF. Therefore, the reader is cautioned against treating a patient with inotropes based on echocar-diographic fi ndings of systolic dysfunc-tion alone.

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review can ventricular function be assessed by

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