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Heart valve disease: mixed valve disease, multiple valve disease, and others 

Heart valve disease: mixed valve disease, multiple valve disease, and others
Chapter:
Heart valve disease: mixed valve disease, multiple valve disease, and others
Author(s):

Philippe Unger

and Gerald Maurer

DOI:
10.1093/med/9780198726012.003.0039
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date: 25 September 2020

Summary

Although most published studies on valvular heart disease have focused on regurgitant or stenotic single-valve disease, multiple and mixed heart valve disease are frequent conditions. In the Euroheart Survey, multiple valve disease accounted for 20.2% of patients included with native valve disease, and multiple valve surgery for 16.8% of all patients undergoing valvular intervention [1]. Data on mixed valve disease are even scarcer, including epidemiological prevalence and natural history. The limited amount of published data on mixed and multiple valve diseases is emphasized both by the European and the American Guidelines, which include a limited number of evidence-based recommendations, mainly on level of evidence C [2,3].

The main aetiologies of mixed and multiple valve disease include rheumatic heart disease (Heart valve disease: mixed valve disease, multiple valve disease, and others Video 39.1), degenerative calcific valvular lesions (Heart valve disease: mixed valve disease, multiple valve disease, and others Video 39.2), infective endocarditis, and secondary cardiac remodelling with annular dilatation and tethered leaflets. Less frequently, it may be due to adverse treatment effects such as thoracic or mediastinal radiation therapy and ergot-derived agonists or anorectic agents, non-cardiac systemic diseases including end-stage renal disease on haemodialysis, carcinoid heart disease, and congenital aetiologies such as connective tissue disorders (including Marfan syndrome and Ehler–Danlos syndrome), and other rare congenital disorders (trisomy 18, 13, 15, etc.) [4].

Video 39.1 Rheumatic valve disease: mitral stenosis and mixed aortic valve disease.

Video 39.2 Calcific degenerative valve disease: mitral and aortic stenosis.

In rheumatic heart disease, mitral regurgitation (MR) is the commonest echocardiographic diagnosis, but mixed mitral valve disease, combined aortic and mitral valve disease, and functional tricuspid regurgitation (TR) are also frequent. Pure mitral stenosis (MS) and pure aortic regurgitation (AR) are less common.

Echocardiography is currently the preferred method for assessing patients with mixed and multiple valve disease and, as with patients with single-valve disease, it should evaluate the aetiology, the mechanism(s) of dysfunction, as well as its consequences, particularly the effects on left and right ventricular function and upon the pulmonary circulation. Detailed evaluation of valve morphology is essential for assessing the possibility of repair.

Specific issues in imaging these patients include the following: (1) the lack of published data; (2) the fact that, typically, most indices of valvular regurgitation and of stenosis severity have been validated in patients with single-valve/single-lesion disease; and (3) the presence of haemodynamic interactions (Heart valve disease: mixed valve disease, multiple valve disease, and others Box 39.1).

The management of patients with mixed and multiple valve disease should take into account the large heterogeneity in terms of aetiologies, combinations, and severity of valve lesions. It should mainly follow the recommendations applied to the dominant lesion. In the presence of balanced lesions, a global assessment of the consequences of the lesions is even more important than the use of isolated indices of severity of stenosis or regurgitation. Whereas according to current guidelines, surgery should only be considered if single-valve isolated stenosis or regurgitation is severe [2,3], it should also be considered in the presence of two or more non-severe lesions in combination causing symptoms, left ventricular (LV) dysfunction, and/or increasing pulmonary pressure. The interactions between valve lesions may significantly impact the echocardiographic diagnosis (Heart valve disease: mixed valve disease, multiple valve disease, and others Table 39.1), and the clinician should be aware of the specific diagnostic pitfalls. Planimetry of stenotic lesions, and assessment of the effective regurgitant orifice (ERO) and vena contracta of regurgitant lesions are less dependent on loading condition and should be preferred.

Table 39.1 Main diagnostic caveats, and preferred methods for multiple and mixed valve disease assessment

… the diagnosis of the following lesion might be impaired

AS

AR

MS

MR

In the presence of

AS

n/a

Pressure half-time method unreliable

Use: vena contracta, PISA

Multiparametric analysis

Low-flow low-gradient MS may occur

Pressure half-time method unreliable

Use: planimetry, or continuity equation if planimetry not feasible

High Reg Vol; increased area of mitral regurgitant jet using colour flow mapping

ERO less affected

Use: ERO

Vena contracta

Doppler volumetric method applicable

AR

Simplified Bernoulli equation may be inapplicable

Gorlin formula using thermodilution invalid

Use: continuity equation

n/a

AR jet should not be mistaken for MS jet

Continuity equation unreliable

Use: mitral orifice planimetry; PISA method applicable

Doppler volumetric method inapplicable

Use: PISA method

MS

Low-flow low-gradient AS frequent

Use: continuity equation

MS may blunt the hyperdynamic clinical picture

Use: vena contracta, PISA

Multiparametric analysis

n/a

Not significantly affected

Use: PISA method

Doppler volumetric method applicable

MR

Low-flow low-gradient AS

MR jet should not be mistaken for the AS jet

Use: continuity equation

Doppler volumetric method inapplicable

Pressure half-time method may be unreliable

Use: vena contracta, PISA

Multiparametric analysis

Continuity equation unreliable

Pressure half-time method unreliable

Gorlin formula using thermodilution invalid

Use: mitral orifice planimetry

n/a

AR, aortic regurgitation; AS, aortic stenosis; ERO, MR effective regurgitant orifice; MR, mitral regurgitation; n/a; not applicable; MS, mitral stenosis; PHT, pressure half-time; PISA, proximal isovelocity surface area method; Reg Vol, MR regurgitant volume.

Reproduced from Heart, Unger P, Rosenhek R, Dedobbeleer C, Berrebi A, Lancellotti P, 97, 272–7, copyright notice 2011 with permission from BMJ Publishing Group Ltd.

The diagnosis of multivalvular heart disease may become even more challenging in situations where constrictive or effusive pericarditis, restrictive cardiomyopathy, and conduction system abnormalities coexist, as in radiation-induced valvular heart disease.

By preventing future reoperation, patients undergoing surgery for a given culprit valvular lesion may benefit from concomitant treatment of another, haemodynamically non-severe lesion.

We will hereafter review the available evidence on the use of echocardiography in mixed and multiple valve disease, emphasizing the specific pitfalls associated with these complex conditions.

Mixed valve disease

Aortic stenosis and aortic regurgitation

AR pressure half-time may be either prolonged in the presence of LV hypertrophy with impaired relaxation, or shortened if there is elevation in LV diastolic pressure [5]. The presence of more than moderate AR may increase the LV outflow tract velocities, which may therefore be not negligible within the Bernoulli equation to assess the pressure drop across the aortic valve. Maximal forward aortic velocity assessed by continuous wave (CW) Doppler, which reflects the combined severity of both aortic stenosis (AS) and AR might be of prognostic value in patients with moderate or more AS, moderate or more AR, and preserved LV function [6].

Preferred methods

When LV outflow tract peak velocities are above 1 m/s, the following formula should be used for assessing the pressure gradient (PG) across the aortic valve: PG = (V22 − V12), where V2 = transvalvular velocities are obtained with CW Doppler and V1 = LV outflow tract velocities with the pulsed wave Doppler modality.

The continuity equation remains accurate for aortic valve area calculation. As recommended in pure AR, assessment of AR in mixed aortic valve disease should be based on a multiparametric integrative approach of qualitative and quantitative parameters using colour- flow, pulsed wave, and CW Doppler imaging.

Mitral stenosis and mitral regurgitation

Valve description and MR quantitative assessment are crucial in MS for guiding the choice of intervention. More than mild MR is a relative contraindication to percutaneous mitral commissurotomy. After the procedure, MR resulting from leaflet tearing is an incentive to perform earlier surgery.

Because of the increased forward flow across the stenotic mitral valve, an E-wave velocity exceeding 1.5 m/s cannot be used as a supportive sign of severe MR in the presence of concomitant MS.

The continuity equation, which assumes a similar flow across the mitral valve and the LV outflow tract, is inherently invalid in mixed mitral valve disease and may contribute to mitral valve area underestimation. Similarly, because of altered LV compliance, the pressure half-time method for assessing mitral valve area may also be unreliable [7].

Preferred methods

Planimetry for assessing mitral valve area is theoretically independent of loading conditions and is the method of reference in patients with rheumatic mitral valve disease. However, planimetry may be unreliable in patients with inappropriate acoustic windows and in the presence of severe calcifications, where intense shadowing may occur and is, therefore, usually not appropriate in degenerative calcific mitral valve disease.

The presence of concomitant MS does not affect the MR ERO assessed by the proximal isovelocity surface area (PISA) method. Similarly, in the presence of MR, the PISA method to assess a stenotic mitral valve area remains accurate.

Multiple valve disease

Aortic stenosis and mitral regurgitation

In order not to overestimate the aortic pressure gradient, proper recognition of AS and MR jet envelope is crucial. The timing of the flow onset allows differentiation of the jets: the MR jet starts within the QRS complex, whereas the onset of the AS is delayed until after the LV isovolumic contraction (Heart valve disease: mixed valve disease, multiple valve disease, and others Fig. 39.1).

Fig. 39.1 Continuous wave Doppler flow recording demonstrating the higher velocity and earlier onset of mitral regurgitation (upper panel) as compared to the aortic stenosis jet (lower panel).

Fig. 39.1
Continuous wave Doppler flow recording demonstrating the higher velocity and earlier onset of mitral regurgitation (upper panel) as compared to the aortic stenosis jet (lower panel).

Because moderate or severe MR reduces the forward flow, the detection of a low pressure gradient despite severe AS is not unusual. The acute MR downgrading that may occur following an isolated aortic valve replacement emphasizes the load dependence of MR in this situation. The high AS-induced intraventricular systolic pressure level increases the mitral regurgitant volume and the surface of colour flow jet assessed by planimetry; mitral ERO is less affected and should be assessed in this setting [8]. A functional aetiology of MR, particularly in the presence of a poorly contracting dilated LV, suggests a potential for reverse remodelling and is associated with an increased likelihood of MR improvement after aortic valve replacement [9]. Conversely, primary MR is less likely to improve. Other predictors of poorer MR improvement include the presence of atrial fibrillation, pulmonary hypertension, marked left atrial dilatation, and patient prosthesis mismatch [911].

Owing to preload and afterload contrasting features, MR and AS have opposite effects on ejection phase indices of myocardial performance, which may have clinical implications: mild LV dysfunction may be masked by the coexistence of MR. Conversely, markedly depressed LV ejection fraction in a patient with severe MR might improve after double valve replacement, due to the favourable postoperative unloading effect of aortic valve replacement (Heart valve disease: mixed valve disease, multiple valve disease, and others Video 39.3).

Video 39.3 Calcific degenerative aortic stenosis and degenerative mitral regurgitation. Despite severe preoperative left ventricular dysfunction, ejection fraction eventually improved after double valve replacement.

Preferred methods

The continuity equation is accurate for aortic valve area calculation. Mitral ERO and vena contracta measurement should be included in MR assessment. The Doppler volumetric method can be used for MR assessment, but mitral inflow diameter may be difficult to determine in patients with calcified degenerative mitral valve.

Aortic stenosis and mitral stenosis

The detection of a low-gradient severe AS, even if LV ejection fraction is preserved and/or of a low gradient in severe MS is not infrequent, highlighting the importance of estimating valve areas.

In the presence of AS, the pressure half-time method for estimating mitral valve area is unreliable, because of LV hypertrophy and impaired LV relaxation. It might be shorter than expected, resulting from a faster equilibration of left atrial and LV pressures, which eventually result in mitral valve area overestimation [12].

Planimetry of the limiting orifice at the leaflet tips is the echocardiographic method of choice for mitral valve area assessment in rheumatic MS. In degenerative MS, planimetry is often unreliable due to the presence of heavy annulus calcifications, where the limiting orifice is located.

Preferred methods

Direct planimetry by two- and three-dimensional echocardiography is most useful for mitral valve area assessment in the presence of rheumatic MS [13]. In the presence of calcific degenerative MS, the use of the continuity equation for mitral valve area determination is advocated as it has been shown to correlate well with invasive measurements, provided that there is no concomitant significant MR or AR.

Tricuspid regurgitation and left-sided valve disease

Secondary TR may result from annular dilation and right ventricular enlargement due to chronic pressure overload as a consequence of left heart valve disease (Heart valve disease: mixed valve disease, multiple valve disease, and others Video 39.4). Mitral valve disease is associated with a higher prevalence of TR than aortic valve disease [14]. Tricuspid surgery is recommended at the time of left-sided valve surgery if TR is severe [2,3]. Functional TR frequently does not disappear after successful left heart valve surgery, and, if left untreated, will adversely affect perioperative outcomes, functional class, and survival. Non-severe TR cannot be ignored when performing left heart valve surgery, considering the high mortality rate for reoperations for recurrent TR. Therefore, European guidelines recommend that tricuspid valve surgery (usually ring annuloplasty) should also be considered in patients with mild or moderate functional TR, when tricuspid annulus is dilated (> 40 mm or >21 mm/m2 as measured from the middle of the septal annulus to the middle of the anterior annulus in the four-chamber view, in late diastole at the time of maximal tricuspid opening) (Heart valve disease: mixed valve disease, multiple valve disease, and others Fig. 39.2) [2,15].

Video 39.4 Rheumatic mitral valve disease and secondary tricuspid regurgitation.

Fig. 39.2 This patient with severe mitral stenosis scheduled for surgery presents also tricuspid regurgitation (a), which is moderate, according to the PISA method (b), the collapsibility of the inferior vena cava and the lack of systolic flow reversal in the hepatic veins (c). There is no evidence for significant pulmonary hypertension (b). The tricuspid annulus as measured from the apical four-chamber view in late diastole is dilated (42 mm). This situation represents a class IIa indication for concomitant tricuspid annuloplasty according to current guidelines [2,3].

Fig. 39.2
This patient with severe mitral stenosis scheduled for surgery presents also tricuspid regurgitation (a), which is moderate, according to the PISA method (b), the collapsibility of the inferior vena cava and the lack of systolic flow reversal in the hepatic veins (c). There is no evidence for significant pulmonary hypertension (b). The tricuspid annulus as measured from the apical four-chamber view in late diastole is dilated (42 mm). This situation represents a class IIa indication for concomitant tricuspid annuloplasty according to current guidelines [2,3].

When severe, primary tricuspid valve disease may blunt the full haemodynamic picture of left-sided stenotic valve disease, by reducing the flow rate and thus the pressure gradient. In this situation, the right-sided clinical signs will be prominent. Moreover, LV filling may be impeded by right ventricular dysfunction and overload, and thereby induce, or, conversely reduce MR.

Aortic regurgitation and mitral regurgitation

This specific combination is usually associated with high LV filling pressure and may present with severe LV dilatation and dysfunction (Heart valve disease: mixed valve disease, multiple valve disease, and others Video 39.5). However, functional MR seems infrequent in the setting of AR [16].

Video 39.5 Left ventricular dilatation and dysfunction in a patient with severe mitral and aortic regurgitation.

Because of unequal aortic and mitral forward flow, the Doppler volumetric method using mitral inflow and LV outflow tract stroke volume assessment cannot be used for quantifying any of the two lesions. Pressure half-time of AR may be shortened in the presence of MR-induced increased LV diastolic pressure.

Diastolic MR, a marker of premature mitral valve closure suggesting poor haemodynamic tolerance, should be assessed in the presence of acute AR (Heart valve disease: mixed valve disease, multiple valve disease, and others Fig. 39.3).

Fig. 39.3 Premature mitral valve closure with diastolic mitral regurgitation in severe acute aortic regurgitation, assessed by colour M-mode (left panel), continuous wave (middle panel), and pulsed wave Doppler (right panel) modalities. The arrows denote the onset of diastolic mitral regurgitation.

Fig. 39.3
Premature mitral valve closure with diastolic mitral regurgitation in severe acute aortic regurgitation, assessed by colour M-mode (left panel), continuous wave (middle panel), and pulsed wave Doppler (right panel) modalities. The arrows denote the onset of diastolic mitral regurgitation.

Preferred methods

PISA and vena contracta width methods are accurate for assessing MR in the presence of AR. The assessment of AR requires a multiparametric integrative evaluation.

Aortic regurgitation and mitral stenosis

The lower velocity and later onset of the MS jet allow differentiation from the AR jet (Heart valve disease: mixed valve disease, multiple valve disease, and others Fig. 39.4). Therefore, AR is accurately confirmed by the detection of signals within the isovolumic relaxation period [17].

Fig. 39.4 Continuous wave Doppler flow recording demonstrating the lower velocity and later onset of mitral stenosis jet compared to the aortic regurgitation jet.

Fig. 39.4
Continuous wave Doppler flow recording demonstrating the lower velocity and later onset of mitral stenosis jet compared to the aortic regurgitation jet.

Because aortic and mitral anterograde aortic flow are unequal, the continuity equation using the LV outflow tract diameter and flow results in mitral valve area overestimation. In the presence of more than mild AR, the MS pressure half-time may be shortened, eventually leading to mitral valve area overestimation. In the study of Flachskampf et al., the calculated mitral valve area was overestimated by an average of 0.2 cm2 [18]. This effect is, however, moderate and individually unpredictable because of the opposite effect of improved changes in chamber compliance. As compared to catheterization, the average bias (0.42 cm2) of the pressure half-time method may have important clinical implications in patients with severe AR [19].

Preferred methods

Mitral valve planimetry is theoretically independent of loading conditions. The PISA method is not influenced by the presence of AR and allows an accurate estimation of mitral valve area [20]. Quantification of AR severity should be based on a multiparametric integrative approach.

Tricuspid and pulmonic valve disease

Severe TR may cause underestimation of pulmonary valve stenosis severity by decreasing pulmonary flow and, hence, pressure gradient. Similarly to MR in patients with AS, the relief of pulmonary stenosis by pulmonary balloon valvuloplasty or by pulmonary valve replacement may reduce the severity of TR through a reduced systolic transtricuspid driving pressure and reduction in right ventricular size [21,22].

Subvalvular and supravalvular stenosis

Subaortic stenosis

Subaortic stenosis can present either as a discrete membrane or as a fibromuscular ring in the LV outflow tract. A progression from membrane to muscular hyperplasia as a consequence of the turbulent flow has been postulated [23]. Subaortic stenosis can be seen in combination with other congenital malformations, including bicuspid aortic valve, aortic coarctation, perimembranous ventricular septal defect, and an obstructive muscle bundle in the right ventricle [24].

Distinction between subaortic stenosis and valvular AS can be difficult on clinical grounds alone. In some instances, subaortic and valvular AS can occur in combination. Subaortic stenosis is usually associated with AR, which is presumably the consequence of chronic damage to the aortic leaflets by the high-velocity systolic outflow tract jet. Surgical resection of the subaortic obstruction is the treatment of choice for symptomatic patients. Even in asymptomatic patients resection has been proposed in order to prevent the damage to the aortic valve that might result in progressive AR [25]. This issue, however, remains controversial since development of AR has been seen even after resection of the membrane.

Echo-Doppler evaluation

The subaortic membrane is usually best visualized in a long-axis view. At times it is more easily seen from an apical (Heart valve disease: mixed valve disease, multiple valve disease, and others Fig. 39.5) or low parasternal window than in standard parasternal long-axis view, and transoesophageal echocardiography usually offers excellent visualization (Heart valve disease: mixed valve disease, multiple valve disease, and others Video 39.6).

Fig. 39.5 Apical view showing a subaortic membrane.

Fig. 39.5
Apical view showing a subaortic membrane.

Video 39.6 Subvalvular membrane in the left ventricular outflow tract as seen by transoesophageal echocardiography.

The subaortic membrane can be seen protruding into the outflow tract along the surface of the interventricular septum and often extends to the base of the anterior mitral leaflet, where tethering can be seen. Indeed, the appearance of a basal anterior mitral leaflet hinge point can be the first echocardiographic clue to search for the presence of the subvalvular membrane.

Colour Doppler shows flow acceleration and turbulence below the level of the aortic valve (Heart valve disease: mixed valve disease, multiple valve disease, and others Fig. 39.6; Heart valve disease: mixed valve disease, multiple valve disease, and others Video 39.7). At times, especially in milder cases, turbulent flow in the LV outflow tract may be the first echocardiographic clue towards its presence. In addition, the regurgitant flow signal of AR can be visualized.

Fig. 39.6 Same patient as in Fig. 39.6. Colour Doppler shows flow acceleration and turbulence below the level of the aortic valve.

Fig. 39.6
Same patient as in Fig. 39.6. Colour Doppler shows flow acceleration and turbulence below the level of the aortic valve.

Video 39.7 Same patient as in Video 39.6. Colour flow Doppler showing flow acceleration at the level of the membrane.

CW Doppler shows a velocity profile that is very similar to the one seen in valvular AS (Heart valve disease: mixed valve disease, multiple valve disease, and others Fig. 39.7). The peak velocity occurs near mid-systole, unlike the late peaking, dagger-shaped velocity profile seen in hypertrophic obstructive cardiomyopathy. With isolated subaortic stenosis the effective gradient can be reliably calculated using the modified Bernoulli equation. In case of serial obstructions, where subaortic stenosis is combined with valvular stenosis or obstructive hypertrophic cardiomyopathy, it may be difficult to sort out the magnitude of each component to the obstruction.

Fig. 39.7 Same patient as in Figs 39.6 and 39.7. CW Doppler shows a peak velocity occurring near mid-systole, very similar to that seen in valvular aortic stenosis.

Fig. 39.7
Same patient as in Figs 39.6 and 39.7. CW Doppler shows a peak velocity occurring near mid-systole, very similar to that seen in valvular aortic stenosis.

Supravalvular aortic stenosis

Supravalvular AS is a rare congenital malformation characterized by narrowing above the level of the aortic valve. Its most common form is the hourglass deformity, followed by diffuse hypoplasia and by a discrete membranous form.

Supravalvular AS usually occurs in association with other congenital abnormalities, such as Williams syndrome (mental retardation, failure to thrive, ‘elfin’ face, and multiple peripheral pulmonary artery stenosis), or with idiopathic infantile hypercalcaemia.

Echo-Doppler evaluation

The ascending aortic morphology needs to be carefully examined from multiple windows. The diameter of the tubular portion should normally never be smaller than the aortic annulus [26]. In addition, the ascending aortic flow needs to be evaluated by colour and CW Doppler and assessed for the presence of a supravalvular gradient. It is important to keep in mind that in this setting, Doppler gradients frequently overestimate catheter gradients because of the pressure recovery that occurs in a tubular stenosis [26].

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