6
Valvular Disorders

1. MITRAL REGURGITATION

I. Mechanisms of mitral regurgitation

The mitral valve anatomy is shown in Figure 6.1. Normally, each papillary muscle provides chordae to both leaflets. The free edges of the leaflets coapt over a length of several millimeters, at a depth of 5–10 mm from the mitral annular plane.

Mitral valve competence depends on: (a) appropriate ventricular contractility that pushes the papillary muscles, chordae, and valvular leaflets up (mitral closing force); (b) appropriate chordal length and tension that restrain the leaflets from prolapsing in the LA; (c) slim leaflet tissue that allows a tight seal in systole (as opposed to a bumpy, redundant tissue).¹

There are four major mechanisms of mitral regurgitation (Carpentier’s classification) (Figure 6.2):²

Type I: MR occurs despite normal leaflet motion and leaflet tip position. Type I MR may occur with leaflet tear(s) secondary to endocarditis or blunt trauma.
Type II: Prolapse of one or both leaflets, i.e., the billowing body of the leaflet is >2 mm above the annular plane (the free edge of the leaflet is at the annular plane or above it). If, in addition to the prolapse of the leaflet body, the free edge is overriding the other leaflet and turned towards the LA rather than the LV, the leaflet is called a flail leaflet; this is usually secondary to chordal rupture and a piece of chordae is usually seen flopping in the LA. Type II MR may also result from papillary muscle rupture (MI).
Type IIIa: The leaflets and chordae are thickened, retracted, and shortened, with chordal fusion (rheumatic or rheumatic-like process). The mitral motion is restricted in both systole and diastole, potentially leading to both MS and MR.
Type IIIb: Functional MR. A localized, inferior ventricular dysfunction pulls the papillary muscle(s) and chorda(e) posterolaterally, predominantly restricting the motion of the posterior leaflet (leaflet tethering). In severe global LV dysfunction, the ventricular geometry changes from an ellipse to a sphere, which pulls both leaflets posterolaterally and apically, restricting their closure. Three additional mechanisms contribute to MR: (a) annular dilatation, which reduces leaflet coaptation; (b) reduced LV systolic pressure, which reduces the mitral valve closing force and sometimes leads to MR even when tethering is mild; (c) papillary muscle dyssynchrony in some patients with LBBB or RV pacing: one ventricular wall contracts while the other is relaxed; therefore, one leaflet is pushed up while the other is still down, which creates a gap between the two leaflets.

II. Specifics of various causes of mitral regurgitation

A. Acute MR

Causes of acute MR:

Mitral valve endocarditis: the vegetations may interfere with proper leaflet coaptation or may destroy and perforate the leaflet(s) or chorda(e)
Papillary muscle rupture occurring in the context of an acute MI
Chordae tendinae rupture. Causes: idiopathic, mitral valve prolapse, endocarditis, trauma
Acute functional MR secondary to an acute ventricular process (MI, myocarditis), even without papillary muscle rupture

In acute MR, EF increases to allow an increase in total stroke volume, the forward stroke volume remaining, however, low. The patient is in shock with pulmonary edema, LA pressure is severely increased, yet the intrinsic LV function is normal, and the LV diastolic pressure may be normal.

Blunt chest trauma during the isovolumic contraction may lead to acute MR (rupture of the papillary muscles, chordae, or leaflets).

Image described by caption. — **Figure 6.1** **(a)** Illustration of a horizontal cut across the mitral plane on transthoracic echocardiography, showing the relationship of the cusps with the papillary muscles, aortic valve, and left atrial appendage (LAA). Also, illustration of how various TEE rotations cut the mitral valve. Note that the anterolateral and posteromedial papillary muscles (APM and PPM) are located between the two leaflets rather than underneath the corresponding leaflet (they are underneath the commissures). A₁–A₃ are various anterior leaflet cusps, and P₁–P₃ are various posterior leaflet cusps (A₃ and P₃ are the ones attached to the septum). The mitral annulus surrounding the anterior leaflet and connecting the anterior leaflet with the aortic valve is fibrous and relatively straight, and forms the *mitroaortic curtain or fibrous trigone*. The posterior mitral annulus has a C shape and is muscular.

**(b)** Illustration of how the mitral valve looks surgically when approached from inside the LA through the anterior heart/RA. A₃ and P₃ are on the right (flipped view in comparison with TTE).

**(c)** 3D TEE view of the mitral valve (en face view). This view is similar to the surgical view. For orientation, identify the anterior leaflet (leaflet with the convex border) and the posterior annulus. The posterior annulus has a C shape, is muscular and contractile. It contracts in systole and contributes to the mitral valve competence. There are two commissures: anterolateral (AL_c), next to the LAA, and posteromedial (PM_c).Note: When approached from a side, both the mitral and tricuspid annuli are *saddle-shaped*, not flat.

B. Degenerative mitral valve disease or mitral valve prolapse (MVP)

MVP (Figure 6.3) is defined as:

One or two cusps prolapse >2 mm into the LA above the annulus level, in the long-axis view
Thick cusps ≥ 2 mm (myxomatous, redundant valve)
Cusp/chordae elongation

There are two forms of MVP:^1,3 (1) mitral fibroelastic deficiency, wherein the prolapsed leaflet(s) are thin (i + iii); (2) Barlow’s disease or classic MVP, wherein the prolapsed leaflets and chordae are thick (i + ii + iii). Fibroelastic deficiency is a local disease that usually affects a single cusp, with the remaining cusps being normal and non-prolapsed. These patients typically do not have a long history of murmur, and MR may appear and progress rapidly (months), with a frequent chordal rupture. Conversely, Barlow’s disease is a chronic process (years) associated with a long history of click or murmur and with thickening of the whole valve. Fibroelastic deficiency is most common in older patients (>50 years old), while Barlow’s disease is most common in patients <50 years of age, often women, may be associated with connective tissue disorders (e.g., Marfan), and may have a familial predisposition.

Fibroelastic deficiency is the most common cause of severe intrinsic MR requiring surgery.

A prolapse seen in the apical four-chamber view is less specific and should not be used to define MVP.

Schematic illustration of carpentier’s classification of the mechanisms of mitral regurgitation. — **Figure 6.2** Carpentier’s classification of the mechanisms of mitral regurgitation.

**Type I:** Normal mitral leaflet motion with the free edges positioned 5–10 mm below the mitral annular plane (saddle- shaped mitral valve). Normally, the leaflets coapt over a minimum length of 2 mm. Type I MR may occur with a leaflet tear secondary to endocarditis or blunt trauma.

**Type II:** Prolapse of one or both leaflets. The billowing body of the prolapsed leaflet is over 2 mm above the annular plane. The free edge may be above the annular plane, less markedly than the leaflet body. When the free edge is significantly prolapsed and looking into the LA rather than the LV, the leaflet is called a *flail leaflet*.

**Type IIIa:** Rheumatic or rheumatic-like process. The leaflets and chordae are thickened, retracted, and shortened, with chordal fusion. The mitral motion is restricted in systole and diastole, potentially leading to both MS and MR.

**Type IIIb:** Ventricular dysfunction pulls the papillary muscle(s) and chorda(e) posterolaterally, restricting the motion of one or both leaflets, predominantly the posterior leaflet.

Schematic illustration of mitral valve prolapse. — **Figure 6.3** Mitral valve prolapse. The long-axis view defines prolapse, while the short-axis view defines which cups are involved (particularly when color Doppler is added).

Notes on MVP (degenerative MV disease)

MVP is usually benign and occurs in 1–2% of the population with a familial trend. Female-to-male ratio = 2:1.
MVP most commonly involves the posterior leaflet, especially the posterior cusp P₂. While two-thirds of MVPs are posterior MVPs, the anterior leaflet (often A₂) or both leaflets are involved in one-third of the cases. When confined to a single cusp, the prolapsed or the flail leaflet may be missed by TTE: TTE shows MR, often very eccentric, hugging the LA wall and underestimated in some views, without obvious structural abnormality. The jet is directed opposite to the prolapsed leaflet.
MVP may be associated with tricuspid prolapse (in ~40%) and aortic valve prolapse (in ~10%).
15% of MVP cases are severe, meaning that they progress to severe MR at a mean follow-up duration of 15 years.
Risk factors for severe MVP:○
- Man > 50 years old. MVP in an elderly patient is generally more serious than MVP in a young woman
- Very thick valve (≥5 mm)
- Significant MR at baseline with MR murmur
Classic MVP, even without significant MR, significantly pulls and stretches the papillary muscle and may eventually engender a local injury and scar. This may cause frequent PVCs and rarely, VT and sudden death.
MVP, regardless of its severity, can be associated with autonomic dysfunction (e.g., orthostatic intolerance) and atypical complaints (chest pain, fatigue, palpitations).

C. Functional ischemic MR and functional non-ischemic MR (Figures 6.4, 6.5)

Ischemic MR is not a valvular problem; it is a problem of segmental ventricular distortion and, to a lesser extent, increased ventricular sphericity. A posterior change in LV geometry tethers the posterior papillary muscle posterolaterally; consequently, both leaflets are tethered, predominantly the posterior leaflet, as it is orthogonal to the posterior papillary muscle. In fact, local geometric remodeling that specifically tethers the posterior papillary muscle is a more important determinant of ischemic MR than global LV remodeling, global LV sphericity, LV dilatation, or EF.³ Severe MR may be seen with a relatively preserved EF: the majority of patients with ischemic MR secondary to inferior MI have a normal or a mildly reduced EF and a normal LV volume. Studies have shown a higher incidence and greater severity of ischemic MR in patients with inferior as opposed to anterior MI, despite a lower EF and more LV dilatation in anterior MI.⁴ This is related to the greater local geometric remodeling seen with inferior MI causing greater posterior papillary muscle displacement. For a given LV volume, local posterior LV remodeling is the determinant of MR severity.⁵

Overall, ~80% of cases of ischemic MR are associated with inferior or inferolateral MI (RCA or LCx), while 20% are associated with anterior MI (LAD),^4,5 although some series found that anterior MI is responsible for ~50% of ischemic MR.^6–8 In two studies of ischemic MR, approximately half the patients had inferior MI, half had anterior MI, and a quarter had infarcts in both territories, with a mean EF of 35–40%.^6,8

Anterior ventricular dysfunction, which exerts longitudinal tension on the anterior papillary muscle and the leaflets, does not lead to enough oblique tethering to provoke MR. Tethering relates to posterior and apical rather than anterior shift of the papillary muscles, directing papillary muscle tension away from the axial direction that closes the leaflets.^4,9,10 This explains why anterior MI cannot provoke ischemic MR unless global remodeling and posterolateral and apical tethering, usually of both papillary muscles, occurs.⁷ Ischemic MR that occurs with anterior MI is, thus, associated with a much lower EF, a larger LV volume, and a larger and more symmetric annular dilatation.⁷ Global remodeling may apically tether both leaflets equally (symmetric tethering with central jet); it may also tether the posterior leaflet more prominently, leading to a posterior jet (asymmetric tethering).¹⁰

Note that annular dilatation, by itself, is not the primary driver of functional MR. The ratio of leaflet area to annular surface area being normally>2:1, very severe annular dilatation would be required to cause inadequate mitral coaptation. Annular dilatation is, however, a contributing factor in ischemic MR. In addition, the annulus normally has a contractile function in systole, the loss of which reduces the coaptation of the tented leaflet and contributes to MR.

Contrary to an old belief, ischemic MR is not related to ischemic papillary muscle dysfunction. In fact, papillary muscle ischemia, per se, does not usually produce MR; it is the underlying wall dilatation that produces MR.

Functional MR may be secondary to ischemic or non-ischemic global LV dysfunction, with an MR jet that is central or posteriorly directed. Approximately 20% of patients with severe systolic HF have severe MR.

In the setting of acute inferior MI, acute ischemic MR related to leaflet restriction should be distinguished from papillary muscle rupture (the leaflet is restricted in the former vs. prolapsed in the latter). Any process leading to acute ventricular dysfunction may be associated with acute leaflet tethering and acute functional MR. Examples include acute ischemia or infarction, but also takotsubo cardiomyopathy, myocarditis, and postpartum cardiomyopathy.

Schematic illustration of ischemic MR on longitudinal views. — **Figure 6.4** **Illustration of ischemic MR on longitudinal views.** **(a)** Normal valvular anatomy. Both papillary muscles (PM) provide chordae to both mitral leaflets. **(b)** Inferior akinesis with posterolateral displacement of the posterior papillary muscle. This leads to major restriction of the posterior leaflet and minor restriction of the anterior leaflet. The tethering force being more orthogonal to the posterior leaflet, the latter is more restricted than the anterior leaflet. In fact, the anterior leaflet overrides the posterior leaflet. **(c)** Anterior akinesis, by itself, does not lead to major restriction of any leaflet as it pulls the leaflets axially rather than sideways. **(d)** Anterior MI with global LV remodeling and global LV dilatation pulls both the anterior and posterior papillary muscles apically and posterolaterally. The more the LV is dilated and spherical, the more laterally the leaflets are pulled, the more severe the MR. Both leaflets are tethered, and the jet may be central or predominantly posterior (if the posterior leaflet is more tethered than the anterior leaflet). Note that ischemic MR cannot be anteriorly directed: it is either central or posterior.

Functional MR is dynamic

Ischemic MR (or any functional MR) may vary with dynamic changes in LV volume and geometry. Symptomatic patients with an ischemic mild or moderate MR at rest may have dynamic MR that worsens with exercise, i.e., with increased venous return and LV volume.^6,8 The increase in venous return increases LV dimension, leaflet tethering, and annular dilatation, which worsens functional MR. The concept of dynamic MR is an important concept, as it may explain exertional or nocturnal symptoms and pulmonary edema in patients with mild ischemic MR at rest. In this case, MR, LA pressure, and PA pressure increase during exercise or during sleep with the increase in venous return. In fact, as opposed to patients with mild ischemic MR and no pulmonary edema, patients with mild or moderate ischemic MR who present with pulmonary edema usually have dynamic MR that worsens with exercise or at night; this apparently “mild” MR is actually a major contributor to their pulmonary edema. This is proven by stress echocardiography, wherein MR severity and PA pressure worsen without any ECG or echocardiographic signs of ischemia (effective regurgitant orifice area increases by ≥ 13 mm²).⁸

On the other hand, the minority of patients with inferior MI who have a significant improvement in global myocardial contractility and LV systolic volume with exercise may have a reduction in the severity of resting leaflet tethering and MR,⁸ and those patients may have improvement of ischemic MR purely with revascularization.⁸

However, before presuming that dynamic MR is due to a combination of baseline tethering and added loading, always rule out another cause of dynamic MR: off-and-on ischemia. In the latter case, the wall motion abnormality and tethering that drive MR are fleeting rather than persistent, and revascularization will reverse MR. Stress echo will show a dynamic wall motion abnormality coinciding with the dynamic MR.

Avoid assessing ischemic MR intraoperatively. The unloading conditions of anesthesia convert a dynamic, severe ischemic MR into mild MR.

D. Atrial functional MR

Functional MR results not only from LV dilatation but also LA dilatation, even if LV systolic function and size are preserved. This is seen with HFpEF and/or long-standing persistent AF and is called atrial functional MR. Significant functional MR (moderate or severe) is seen in 6-7% of patients with isolated AF and up to 18% of patients with decompensated HFpEF, more so in restrictive cardiomyopathies. This MR dramatically improves with AF rhythm control (in >75% of patients).^11–13

Unlike ventricular functional MR, atrial functional MR is primarily driven by severe annular dilatation and requires severe LA dilatation, more than seen with ventricular MR. Annular dilatation flattens the mitral leaflets and unlike tethering, pulls their coaptation zone up. Thus, unlike ventricular MR, atrial MR is centrally directed rather than eccentric (Figure 6.6).

Also, severe HTN aggravates functional MR. HTN makes it harder for the LV to pump forward, which creates the backward leak. This functional MR quickly improves with HTN control.

E. Rheumatic fever

Rheumatic fever leads to scarring and retraction of the leaflets and the subvalvular apparatus, restricting mitral valve closure (→ MR) and opening (→ MS). A predominant or isolated MR may be seen with rheumatic heart disease.

F. Other causes of MR

Healed, old endocarditis with progressive scarring and retraction of the mitral leaflet(s) may lead to late MR.
Systolic anterior motion of the anterior leaflet and chordae in HOCM.
Severe posterior mitral annular calcifications (MAC). MAC may immobilize the basal portion of both mitral leaflets, preventing their nor- mal excursion in diastole (→ MS) and in systole (→ MR). Also, the mitral annulus loses its expansile function (→ MS) and contractile function (→ MR).

Important situation: severe MR with severe LV dysfunction

MR could be the cause of LV dysfunction (primary MR) or, much more commonly, the result of it (functional or ischemic MR). These two conditions are treated differently: intrinsic MR requires valvular repair, whereas functional MR primarily requires treatment of the underlying LV dysfunction.

Severe organic MR leads to symptoms very long before severe LV dysfunction. Thus, when severe LV dysfunction is associated with severe MR, LV dysfunction is generally the primary issue and MR is usually functional, unless there is a long history of severe MR. The definite diagnosis relies on assessment of the mitral valve structure. If the valve leaflets are thick and prolapsed, MR is organic, whereas if the valve leaflets are thin and normal but restricted in their motion, MR is functional. TEE often helps in that regard, as it provides better leaflet visualization.

Hint for acute presentations: in acute primary MR, LV is hypercontractile, i.e., EF is increased rather than decreased. Acute HF with low EF and severe MR usually implies functional rather than primary MR.

Schematic illustration of atrial functional MR versus LV functional MR. — **Figure 6.6** **Atrial functional MR vs LV functional MR.** In atrial functional MR, the LA and the mitral annulus are more dramatically dilated and leaflet tethering plays a lesser role (anteroposterior mitral annulus >35 mm on long-axis view). Leaflets typically adapt and lengthen to compensate for annular dilatation; insufficient leaflet lengthening contributes to MR. Impaired mitral annular contraction plays a role as well (especially if MAC is present).

III. Assessment of MR severity

A. TTE (see also Chapter 32: Figures 32.24–27, and Table 32.1)

Beside LA enlargement, which is a necessary finding in chronic severe MR, the following are severe MR criteria:

Regurgitant color jet fills >40% of the area of the LA, at a proper color gain and a Nyquist limit of 50–60 cm/s. Eccentric MR is under- estimated by the jet area.
High early mitral inflow velocity (E wave >1.2 m/s) is highly sensitive.
Large PISA, which is the regurgitant jet hemisphere on the side of the ventricle (≥ 0.9 cm at 40 cm/s Nyquist limit); and large effective regurgitant orifice (ERO) area ≥ 40 mm². Note that 30 mm ²better defines severe ischemic MR, which tends to be dynamic and undervalued at rest;^6,8 also, PISA being frequently squashed (flat) rather than round, the short PISA distance underestimates the full PISA area (as the calculation assumes it is round).
A flail leaflet is highly specific for severe MR, regardless of color jet findings (only feature that does not rely on Doppler).
Pulmonary vein systolic flow reversal is mainly seen in decompensated or acute MR and corresponds to the large V wave.

Acute severe MR may look mild on TTE. The increased LA pressure reduces the LV–LA pressure gradient and the MR velocity, which may reduce the color signal and turbulence; also, acute MR may be eccentric. Thus, if a patient has pulmonary edema with a questionable MR severity and a normal or hyperdynamic LV, think of severe MR and perform TEE or left ventriculography.

B. TEE or cardiac MRI for indeterminate MR

TEE is performed if the severity or the cause of MR is unclear by TTE. It is also valuable in planning mitral surgery: assess which cusp(s) is involved and whether repair is feasible. MRI is another excellent modality for assessing valvular pathology and quantifying regurgitant volume.

C. Left ventriculography

Left ventriculography is indicated if the echo data are inconclusive or when there is discrepancy between the echo data and the clinical findings. When properly done, ventriculography is highly accurate in MR grading, as it semi-quantitatively addresses the regurgitant volume rather than velocity. Color doppler frequently underestimates the severity of eccentric MR, as color correlates with velocity more than volume: MR volume may be high, yet color velocity abuts the LA wall eccentrically and quickly abates.

In severe MR, LA entirely fills with contrast, as intensely as LV (=3+ MR), or more intensely than LV, sometimes with pulmonary venous filling (=4+ MR).

D. Right heart catheterization

Right heart catheterization may be performed as an adjunct to left ventriculography when the severity of MR is unclear. The finding of an ample V wave that exceeds 45 mmHg or is twice the mean PCWP suggests severe MR. However, the V wave may not be that ample in severe but compensated MR (Figure 6.7). An ample V wave may also be seen with decompensated HF, even without MR.

In addition, the invasive measurement of PA pressure and PCWP at rest and with stress is valuable in addressing the surgical indication when MR is severe but symptoms are mild and non-specific. An elevated PCWP implies that MR is likely functionally limiting, even if the patient denies any symptom.

E. Stress testing and BNP

Beside an elevated PCWP and PA pressure, a stress test showing a limited exercise tolerance (class IIa), or an elevated BNP, may indicate surgery in patients who deny symptoms.

IV. Natural history and pathophysiology of organic MR

Even among asymptomatic patients with normal LV function, severe MR leads to symptoms or LV dysfunction in 100% of patients at ~5 years. Asymptomatic severe MR is associated with the following yearly risks: 0.8% sudden death, 5–6% cardiac death, 10% combined cardiac death, HF, or AF, and ~20% death or requirement for valvular surgery (fast progression).¹⁴

Schematic illustration of difference in V wave and LV diastolic pressure between (1) chronic compensated MR and (2) acute or decompensated MR. — **Figure 6.7** Difference in V wave and LV diastolic pressure between (1) chronic compensated MR and (2) acute or decompensated MR. In decompensated MR, V wave gets larger, Y descent gets deeper, while X descent gets shallower. LA pressure may switch from (1) to (2) with simple maneuvers: handgrip (↑ afterload), small volume loading, exercise. LA pressure may switch from (2) to (1) with sedation, acute hypertension control, or nitroprusside infusion (↓ preload and afterload). Reproduced with permission from Hanna EB. Mitral regurgitation. In: Hanna EB, Glancy DL. Practical Cardiovascular Hemodynamics. New York, NY: Demos Medical, 2012, p. 112.

Once symptomatic, the mean survival of severe MR is ~3 years without surgical correction.

In chronic MR, the LV pumps a double stroke volume in two directions, including an “easy” low-pressure LA. This explains how EF is increased if LV is normal and is helped early on by the low afterload. LV diastolic size increases to allow an increase in total stroke volume and the maintenance of a forward stroke volume, whereas LV end-systolic size decreases (EF ↑↑). Once LV intrinsic contractility starts to fail, EF decreases toward the normal range and LV end-systolic size starts to increase. An EF of 50–60% is already abnormal and indicates an intrinsic myocardial dysfunction that may not be fully reversed with surgery and may indeed worsen postoperatively. LV afterload is reduced early on but increases with time as LV systolic size increases (wall stress being proportional to LV systolic size).

V. Treatment of organic (primary) MR

A. Surgical indications in primary MR

The patient must have severe MR and one of the following findings:^15–17

Symptoms (functional limitation class II–IV) (class I indication).
EF ≤ 60% or LV end-systolic diameter (LVESD) ≥ 40 mm (class I indication).
Asymptomatic patient with normal EF but moderate pulmonary hypertension (systolic PA pressure >50 mmHg at rest or >60 mmHg with exercise) or new-onset AF (class IIa indication if high likelihood of durable repair). Pulmonary hypertension implies a risk of HF and sympto-matic progression in pauci-symptomatic patients; even lesser degrees of pulmonary hypertension are associated with impairment of long- term survival.¹⁸ As compared to sinus rhythm, AF is associated with excess mortality under watchful management.¹⁹ Also, as opposed to patients with AF >3 months, patients with AF <3 months have a very low recurrence of AF on long-term follow-up after mitral repair, as early LA remodeling is reversed.²⁰
When EF is <30%, MR is usually secondary to LV dysfunction rather than primary. If primary, mitral surgery remains reasonable, especially if MV repair is likely. Mitral surgery is still reasonable if MV repair is not likely but MV replacement with chordal preservation is feasible.
Severe primary MR (class I) undergoing cardiac surgery for another indication. In a patient undergoing AVR, AVR + mitral repair is preferred to double valve replacement (lower operative risk).
MV repair is reasonable in asymptomatic severe MR with EF >60%, normal LV size, and normal PA pressure, as long as the likelihood of successful repair is >95% and the operative mortality <1% (class IIa, mainly for posterior leaflet prolapse). In fact, there is a significant risk of events associated with severe MR during the watchful waiting period, with a doubling of cardiac mortality and quadrupling of cardiac events.^14,21-25 Furthermore, when surgery is performed in symptomatic patients or those with early LV dysfunction, LV dysfunction frequently persists postoperatively or deteriorates. Excess mortality persists after surgery in patients operated with EF ≤60% (especially <50%) or severe symptoms III/IV, whereas life expectancy is restored to normal in patients operated with no or minimal symptoms and EF >60%.^26,27 The 5-year mortality of patients who undergo surgery with EF of 50–60% is almost double the mortality of those with EF >60%, with double the risk of long-term HF and EF deterioration.²⁶ Data suggest an improvement in long-term survival and risk of HF with early intervention in these asymptomatic patients (vs. watchful waiting), as long as mitral repair is performed.^23,25 Early surgery prevents the risk of adverse LV remodeling that occurs in the waiting period or postoperatively. A BNP ≥ 105 pg/ml is also predictive of increased long-term mortality under conservative management.²⁸
Along the same lines as (f), MV surgery (repair or replacement) is reasonable in asymptomatic patients with EF>60% and LVESD<40 mm who, nonetheless, have a progressive increase in LV size or reduction of EF within this normal range on 3 serial echos (class IIb). In fact, one study suggested that LV dysfunction of MR is irreversible once EF <64% or LVESD≥37 mm.^16,29

LV function may deteriorate after mitral surgery:

This is partly related to damaging the subvalvular annular–chordal–papillary muscle continuity during mitral valve replacement, which leads to a change in the LV geometry and the effectiveness of LV contraction. In fact, the LV changes from elliptical to spherical, which strongly limits longitudinal motion.
LV deterioration is also related to the fact that, in MR, mild EF reduction is a sign of an already advanced LV contractile dysfunction that is unveiled by closing the low resistance leak (raising afterload).
Closing the low-resistance leak increases afterload in the immediate postoperative period. This “afterload mismatch” contributes to early EF deterioration. In fact, ~25% of patients with baseline LV dysfunction experience immediate and long-term EF deterioration and HF after mitral valve repair, related to this afterload mismatch . This happens in up to 50% of patients with baseline EF <50% and may even happen in a small number of patients (<10%) with normal EF.²⁶ Yet, afterload mismatch does not worsen long-term EF compared to non-operated patients, as reducing MR reduces LV volume and protects long-term EF.

Mitral valve repair or chordal preservation during mitral replacement lessens LV deterioration (Figure 6.8). Chordal preservation consists of fixing the chordae and attached mitral leaflet pieces to the annulus before implanting the new valve; this way, the chordae suspend the LV to the annulus and prevent sagging and ballooning of the LV.

B. MV repair is preferred to MV replacement in isolated posterior leaflet prolapse limited to less than half of the posterior leaflet (class I), where MV replacement is now contraindicated unless repair has been attempted (class III). It is also indicated with anterior or bileaflet prolapse, when durable repair seems probable (class I).

MV repair preserves the subvalvular apparatus and the LV geometry. Even if MV replacement is performed, the MV apparatus should be preserved and fixed to the annulus rather than resected to preserve the ventricular geometry.
MV repair protects from the LV deterioration that commonly occurs after MV replacement, especially with EF ≤ 60% but even with EF > 60%. MV repair is associated with over 50% improved long-term survival, whether performed for posterior or anterior MVP (vs. MV replacement). In addition, the postoperative mortality after MV repair may be very low (<1%) and approximates half the mortality of MV replacement when expeditiously done (meta-analysis that included Mayo Clinic data).³⁰
MV repair does not necessitate chronic anticoagulation therapy.
Reoperation rate is ~5–10% at 10 years with posterior MVP, and 20–30% with anterior or bileaflet MVP. Reoperation is performed for progressive, recurrent MR, often (70%) related to initial technical failure.
MV repair of a posterior prolapse typically involves resection of the redundant cusp and placement of an annuloplasty ring. Conversely, anterior prolapse consists of a larger area of cusp prolapse that is more difficult to correct. As opposed to resection of the abnormal cusp, repair of an anterior prolapse consists of chordal transfer: a normal segment of the posterior leaflet is identified, cut and attached with its chordae to the unsupported, prolapsed portion of the anterior leaflet (the cut posterior leaflet is then repaired in a sliding fashion). Chordal transfer may also be performed from the belly of the anterior leaflet to its edge; chordal replacement with PTFE chords may also be performed. An annuloplasty ring is placed at the end. Anterior leaflet repair is improved with these techniques, but there is a higher need for reoperation at 10 years (30% vs. 10% for posterior leaflet).

MV repair may, therefore, be more technically challenging than MV replacement and, in case of failure, requires longer pump time, which may not be tolerated in the sickest patients.
Immediately postoperatively, ~10% of patients undergoing MV repair for MVP develop significant SAM of the anterior leaflet with LVOT obstruction and significant MR. This MR may be misdiagnosed as failed repair. SAM is secondary to the anterior leaflet being “squeezed” down into the LV by the narrow annuloplasty ring and therefore touching the septum, particularly if the LV cavity is small and the anterior leaflet is long and redundant. Moreover, the increase in steepness of the mitroaortic angle moves the leaflet coaptation line anteriorly towards the LVOT (Figure 6.8). SAM immediately improves with fluid administration and cessation of inotropic drugs.

C. Medical therapy

Medical therapy does not have a role in primary severe MR, except for the use of ACE-Is or CCBs for an associated hypertension. Vasodilators may reduce regurgitant volume but do not diminish clinical deterioration or LV remodeling.

VI. Treatment of secondary MR (ischemic and non-ischemic functional MR)

While ischemic MR is initiated by ventricular disease, the ventricular function is frequently normal or mildly/moderately reduced. Therefore, ischemic MR frequently becomes the primary driver of functional limitation, pulmonary edema, and progressive LV remodeling, which begets worsening of MR.^6,8 Treating MR may stop this deleterious process. Three questions need to be addressed before deciding to surgically target functional MR.

A. What is the primary driver of HF (MR vs. underlying LV failure)?

MV repair is not likely to help patients with underlying severe LV enlargement (LV end-diastolic diameter >65 mm) or extensive scarring and non-viability, in which case LV is the primary driver of symptoms and events. LV is irreversibly remodeled and will continue to dilate even after mitral correction. This is called proportionate functional MR, i.e. MR severity is simply tracking LV dilatation, not driving it.

Schematic illustration of unlike (a), the chordae are tied to the mitral annulus before implanting the new valve in (b), preserving LV geometry and preventing LV ballooning. — **Figure 6.8** Unlike (a), the chordae are tied to the mitral annulus before implanting the new valve in (b), preserving LV geometry and preventing LV ballooning. In (c), after MVP repair, the elongated anterior leaflet is squeezed down (*arrow*) by the narrow ring, and the mtiroaortic angle becomes more acute (*vertical arrow*), which causes SAM and LVOT obstruction.

B. Will revascularization alone reverse MR?

In most patients, coronary revascularization alone does not correct moderate or severe MR. In two registries of severe MR, ~50% of patients improved their MR with CABG and <10% became mild MR or no MR.^31,32 Up to 70% of patients with moderate MR show an improvement with CABG. The evidence is less compelling for PCI.

Standalone revascularization is expected to improve dynamic MR that is associated with off-and-on dysfunction of a myocardial segment (e.g., ACS) without chronic infarction. This must be distinguished from dynamic MR that results from fluctuations of loading conditions on top of a fixed, chronic myocardial dysfunction. The latter MR usually does not reverse with revascularization, except when it improves with low-dose dobutamine.

C. Can MR therapy reverse the underlying tethering process?

Mitral valve reduction annuloplasty consists of suturing a downsized ring to the endocardial surface of the mitral annulus in order to reduce the annular size. Thus, rather than addressing the underlying LV dysfunction and tethering, annuloplasty attempts to compensate by addressing the other end of the mitral apparatus. This explains the inconsistent and sometimes suboptimal long-term results of annuloplasty. The best results are obtained when a rigid or semi-rigid full-circumference annuloplasty is performed with a ring measured to the anterior leaflet circumference and downsized two sizes (24–28 mm). Posterior bands were used with the thought that the posterior (muscular) annulus is the one that dilates; however, the fibrous anterior annulus dilates as well. An older series using posterior flexible bands failed to show any benefit of mitral annuloplasty in adjunct to CABG.³³ In addition, one study suggested that annuloplasty may lead to functional mitral stenosis.³⁴

In a later case series of patients with severe ischemic MR and mean EF ~30%, CABG + downsized complete annuloplasty showed a sustained improvement in MR, functional status, and reverse remodeling.³⁵ This benefit mainly applied to patients with LVEDD <65 mm, wherein reverse remodeling occurred and 5-year survival was high (80%); patients with enlarged LV were at an irreversible stage of remodeling

and had a low 5-year survival rate (49%) despite annuloplasty. Further support was provided by a STICH trial sub-analysis of patients with severe MR, which suggested improved survival with CABG+ mitral repair vs. CABG only.³⁵ The benefit in moderate ischemic MR is less clear, with one trial showing a lack of benefit and an early hazard of adding annuloplasty to CABG, MR improving in 70% of patients undergoing CABG only (CTSN trial);³⁶ another trial showed benefit on LV end-systolic volume and peak O₂ consumption, at the expense of higher postoperative complications (RIME trial).³⁷ Other techniques that relieve tethering, such as chordal cutting or papillary muscle repositioning, have been used. The perioperative mortality of CABG + mitral annuloplasty is 3% (RIME) to 8%.^35,37

In a trial of patients with severe ischemic MR and moderate EF reduction (40 ± 10%), mitral valve replacement with chordal preservation proved equivalent to annuloplasty repair in terms of survival and reverse remodeling, but provided a more durable MR correction and less HF and repeat hospitalizations at 2 years.³⁸ Most of these patients underwent concomitant CABG (~75%).

All the above data address adjunctive mitral surgery in patients who, for the most part, are undergoing CABG, and mainly show a benefit in patients without a severely enlarged LV. HF and LV remodeling improve, with a less clear survival benefit. The value of mitral correction is more questionable in patients who do not have an indication for CABG. In the latter patients, severe symptoms without severe LV dilatation are compelling evidence that MR is the primary driver of symptoms and LV remodeling; correction of MR may, therefore, be beneficial, preferably with the percutaneous Mitraclip. Medical therapy and CRT, when indicated, are first-line therapy. In fact, CRT improves MR in over 60% of patients with severe functional MR, but may also worsen MR in ~10% of patients.^39,40 This is related to the degree of reverse remodeling (reduction of LV volume) achieved with CRT. An immediate improvement results from coordinated papillary muscle contraction and increased LV pressure, followed by further improvement over the ensuing 3 months.

D. Guidelines for the management of ischemic or non-ischemic functional MR

Guidelines recommend adjunctive mitral surgery in patients undergoing CABG or AVR who have functional severe MR (class IIa, replacement or repair). In patients with mild or moderate ischemic MR, an exercise test addressing dynamic MR further selects patients who are most likely to benefit. Also, unlike the ERO cutoff of 40 mm ²used to define severe primary MR, a cutoff of 30 mm ²better defines severe secondary MR. This is because secondary MR is a dynamic MR, and therefore a resting ERO of 30 mm² generally corresponds to a much larger exertional ERO and hemodynamic impact. Also, a smaller regurgitant volume is more impactful in patients with a low stroke volume (compared to those with a high stroke volume). The 30 mm² cutoff has been prognostically validated in registries and in COAPT trial, and is suggested by ESC guidelines ^6,8,41,42 Yet, ACC guidelines recommend using 40 mm² as a more specific cutoff for surgical decisions, this being the cutoff used in CTSN trials;^36,38 the Mitraclip COAPT trial mainly recruited ERO>30 mm².

Patients with no CABG indication- Patients with severe functional MR who do not have an indication for CABG should receive HF therapy, aggressive hypertension control, and CRT (if indicated) as first-line therapy. The severity of MR improves with diuresis and LV unloading in 40% of patients, even more so if CRT is used for LBBB.⁴³Percutaneous repair with MitraClip may be performed if symptoms are class II–IV despite medical therapy and CRT, and LV is not severely dilated (regardless of whether EF is more or less than 30%) (class IIa in ACC guidelines).¹⁵ In those cases, MR is the biggest driver of HF, more so than LV dilatation, and is called disproportionate functional MR.⁴¹ Conversely, MR correction is less compelling in patients with severe LV dilatation (LV end-diastolic volume>200-250 ml or 96 ml/m², LVESD>6 cm or LVEDD>7 cm), as MR may not be the driver of symptoms or the negative remodeling process: progressive LV dilatation and deterioration may continue despite mitral surgery (proportionate functional MR).⁴⁴

Mitraclip is favored over MV surgery in isolated functional MR (surgery is given class IIb, with a preference for MV replacement).

For atrial functional MR (normal EF) that persists despite AF and HFpEF therapy, MV surgery may be considered (class IIb).

VII. Treatment of acute severe MR related to acute MI

In case of papillary muscle rupture, perform emergent valvular surgery + CABG. Place IABP preoperatively and consider IV vasodilators (nitroprusside) if blood pressure allows, as in all cases of acute severe MR. MV replacement is often performed, as it is difficult to sew necrotic and friable papillary/LV tissue, but repair may be performed in select subacute cases.

In acute severe MR secondary to acute mitral leaflet tethering, treat the patient medically with vasodilators and place IABP for temporary support. It is expected that leaflet tethering will improve once the function of the reperfused territory improves. Surgery should be considered as a second-line therapy for those patients who do not improve with medical therapy.

VIII. Percutaneous mitral valve repair using the Mitraclip device (transcatheter edge-to-edge repair)

The Mitraclip consists of a clip that approximates the edges of both mitral valve leaflets. This creates a double mitral orifice (edge-to-edge repair) and stabilizes the anteroposterior annular dilatation. It is delivered percutaneously through a trans-septal puncture. One or sometimes two clips (~40%) may be needed. The EVEREST II trial randomized patients with both organic (73%) and functional (mostly ischemic) (27%) severe MR to Mitraclip vs. mitral surgery, mostly mitral repair.⁴⁵ At 1 year, a substantial proportion of Mitraclip patients had residual moder- ate (27%) or severe (~20%) MR, and 22% had to undergo mitral valve surgery at 1 year. However, three subgroups of patients seemed to achieve equivalent benefit and equivalent freedom from death and mitral reoperation with Mitraclip: functional MR, patients >70 years old, and patients with EF <60%. Thus, Mitraclip may be more suited for functional MR or high-surgical-risk cases (ACC class IIa). ^15,46–48

COAPT trial in functional MR- In COAPT trial, patients with severe functional MR (ERO mostly >30 mm²), who had failed several months of maximal medical therapy +/-CRT derived a dramatic benefit from Mitraclip (~50% reduction of hospitalizations at 2 years, ~35% vs 67%; ~40% reduction in mortality, 29% vs. 46%). The key in COAPT was to select patients truly refractory to maximal medical therapy whose LV is not severely dilated. In those patients, severe MR is a key driver of further LV deterioration and dilatation, which is stopped by the Mitraclip (disproportionate MR). LV stopped dilating or slightly declined in size in the Mitraclip group, vs. further dilated in the control group. MR was ischemic in 60% of patients, and mean EF was 31% (20-50%). LVESD was mostly <6 cm, LVEDD was <7 cm, ERO was 40 +/-15 mm², and PA systolic pressure was ≤70 mmHg.⁴² In contrast, the less selective MITRA-FR trial, which recruited patients with less severe functional MR, more dilated LV and less aggressive medical therapy attempt failed to show a benefit of Mitraclip.⁴⁹

Anatomically, when Mitraclip is used for functional MR, the coaptation depth must be <11 mm below the annulus and the leaflets must coapt over >2 mm. When used for degenerative MR, the following are exclusion criteria: severe flail (gap between leaflets ≥ 10 mm in height or ≥15 mm in width), bileaflet flail, or severe bileaflet prolapse.

2. MITRAL STENOSIS

I. Etiology and natural history

Mitral stenosis (MS) is usually secondary to rheumatic fever and occurs a couple of decades after the initial infection, as the injured valve gets progressively traumatized by the turbulent blood flow. Rheumatic MS is more common in women (2:1), and occurs at a young age in third-world countries (20s–30s) vs. a later age in developed countries (role of recurrent infections?).
The fibrotic process initially involves the mitral commissures and the leaflet edges, and manifests as commissural fusion. The process then progressively involves the whole valve and subvalvular apparatus with progressive calcifications. The leaflets and subvalvular apparatus (chordae) are thickened, fused, and progressively calcified.
The subvalvular apparatus shortens and pulls on the leaflets, potentially creating rheumatic MR beside MS.
Symptoms progress more slowly than with other valvular disorders (it takes 5–10 years to progress from early functional class II to func- tional class III–IV). Asymptomatic or minimally symptomatic patients with moderate/severe MS often remain so for many years.

Figure 6.9 Difference between rheumatic MS and MAC MS. In rheumatic MS, the leaflets tips are affected and tied together, leading to a funnel-shaped stenosis. In MAC, the obstruction is outward, at the leaflet base, with relatively unrestricted leaflet tip motion and minimal valvular impedance. Beware that patients with MAC and LV failure have large E wave on echo and are often overcalled as MS.
Without surgical or percutaneous therapy for class II or III symptoms, the survival is ~50% at 10 years, which is low yet better than other valvular disorders left untreated. However, class IV patients have a mean survival of <1 year without invasive therapy.^50,51
Other causes of MS:
- Mitral annular calcification (MAC) or senile MS – MAC is related to: (i) aging, (ii) atherosclerotic processes (eg, smoking and diabetes), and (iii) hemodynamic stress on the mitral valve, as caused by severe HTN or even chronic MVP. It is very common in renal disease, and initially develops at the posterior annulus without causing any inflow obstruction. MAC can progress from the posterior annulus and involve the bases of the posterior leaflet, then the anterior leaflet; the valvular edges and commissures remain freely mobile.^52,53 This is opposite to rheumatic MS, which starts at the valvular edges and commissures. Severe MAC rarely leads to MS but may lead to MR (sometimes severe), as MAC impairs annular contraction and the overall leaflet mobility and coaptation. Severe MAC may extend into the adjacent myocardium and papillary muscles, the conduction system, and rarely, the anterior annulus (mitroaortic fibrosa). Since it does not consist of commissural fusion, valvuloplasty is not an effective therapy. Also, annular calcium precludes placement of an adequately sized prosthesis, unless calcium is debrided (which risks rupturing the AV junction). Since MAC mainly narrows the leaflets base rather than the tips, it rarely impedes mitral flow (Figure 6.9). Beware that a mitral gradient in patients with severe MAC does not necessarily mean MS.⁵³ Patients with severe MAC often have diastolic HF and pronounced E wave which creates the false illusion of a gradient; unlike true MS, the E wave has a sharp downslope and on catheterization, the Y descent is steep (see II.B).
- Rheumatic-like inflammatory process – rheumatoid arthritis, lupus, carcinoid syndrome.
- Congenital MS usually consists of a single papillary muscle to which all chordae converge (parachute mitral valve). This chordal convergence restricts valvular opening. It usually presents early in life.

II. Diagnosis (Table 6.1)

A. Echocardiographic features (see also Chapter 32)

Early on, the commissures are fused and the free edges are immobilized, while the body of the anterior leaflet is free-moving. This gives the anterior mitral leaflet a hockeystick shape. The posterior leaflet appears stiff, immobile (Figure 6.10).
On the mitral valve M-mode, the E–F slope is flattened because there is no diastasis in mid-diastole (figure 6.10). The posterior leaflet is pulled toward the anterior leaflet because of the commissural fusion.
The valve and subvalvular apparatus are thick ± calcified. The chordal thickening is particularly well visualized on the apical views.
Commissural fusion ± commissural calcium are seen on the mitral short-axis view and lead to a “fish mouth” shape of the mitral orifice.
On mitral Doppler, E wave is high and its downslope is slow, as E flow is limited by the mitral valve (unlike the E wave of HF or MR, which is high but its downslope is sharp).
Since it is easy to align the Doppler beam with the mitral inflow on the apical views, the echocardiographic determination of the transmitral gradient is highly accurate. However, the estimation of the mitral valve area (MVA) using one of the four echo methods (mitral inflow pressure half-time, continuity equation, PISA method, and planimetry) may be subject to measurement errors, and thus MVA is better assessed with invasive hemodynamics, if needed.

Table 6.1 Severity of MS.

	Mitral valve area	Mean mitral gradient at a normal heart rate (60–80 bpm)
Moderate MS (formerly mild MS)	>1.5 cm²	<5 mmHg
Severe MS	1–1.5 cm²	5–10 mmHg
Very severe MS	≤1 cm²	>10 mmHg

The mitral valve area (4–6 cm² ) is normally larger than the aortic valve area (3–4 cm²). As a result, severe AS is classified as valvular area ≤ 1 cm², while severe MS is classified as valvular area ≤ 1.5 cm². Percutaneous or surgical intervention is indicated in severe MS with symptoms or pulmonary hypertension (systolic PA pressure > 50 mmHg at rest or > 60 mmHg with exercise). Stress gradient may be obtaining with passive leg raising.

MVA is a better determinant of MS severity than the mitral gradient. In fact, transmitral pressure gradient being proportional to the square of the transmitral flow, tachycardia or a high-output state (e.g., anemia, heavy vasodilator use, sepsis) may convert an anatomically mild MS into a hemodynamically severe MS with a severely increased transmitral gradient. Hence, in any echo or invasive study of MS, it is always important to report the heart rate. Heart rate reduction and diuresis may be appropriate first-line therapies in an anatomically mild MS, which underlines the importance of invasive assessment of cardiac output and MVA in selective cases. Overall, invasive hemodynamics are valuable for the assessment of MS whenever there is discrepancy between echocardiographic MVA and a large transmitral gradient; and whenever it is not clear whether the patient’s symptoms or pulmonary hypertension are purely secondary to MS, or rather secondary to mild MS + LV diastolic dysfunction (especially in the MAC subset), mild MS + high-output state and tachycardia, or intrinsic pulmonary arterial hypertension. The invasive calculation of MVA and cardiac output is invaluable in these cases, and is often performed in patients whose echocardiographic MVA is in the mild or moderate range.

Case illustration: a patient with severe diastolic dysfunction and mild/moderate MS (MVA > 1.5 cm²) may have severe LVEDP elevation with a PCWP that is only slightly larger than LVEDP, implying a more dominant role of LV dysfunction in the patient’s symptomatology. Stress testing may be performed: a disproportionate rise of PCWP and transmitral gradient (>15 mmHg) in comparison to LVEDP implies significant MS.

B. Catheterization

If invasive assessment of MS is needed, simultaneous LA–LV pressures should be obtained, and, ideally, LA pressure should be directly measured through a trans-septal puncture. PCWP is sometimes used as a surrogate of LA pressure and PCWP–LV simultaneous recordings are used to assess MS (Figure 6.11). Three pitfalls attend the use of PCWP and lead to overestimation of the transmitral gradient:

PCWP tracing is delayed by 50–150 ms in comparison to LA pressure tracing.
PCWP is more damped than LA pressure with less deep and steep Y descent.
The obtained PCWP may not be a true PCWP and may rather be a damped PA pressure or a hybrid PA–PCWP. True PCWP has well-defined A and V waves with the following characteristics: (1) as opposed to the systolic PA pressure, the V wave of PCWP peaks after the T wave and its peak intersects the LV descent; (2) if a diastolic segment is well seen between pressure peaks, it is horizontal or upsloping with A wave in PCWP vs. downsloping in damped PA pressure; (3) V wave is narrow-peaked with slow upslope and sharp downslope, opposite to PA.

To correct for the phase delay, one may shift the PCWP leftward until the peak of the V wave is bisected by the LV downstroke. Two situations particularly exaggerate the PCWP pitfalls, mandating a trans-septal LA pressure measurement:

Large V wave, where the “spread-out,” damped V downslope creates a false gradient (Figure 6.12).
Pulmonary hypertension. Pulmonary hypertension makes it difficult to wedge the PA and obtain a true PCWP. Even when PCWP is obtained, it is usually a damped, flat tracing that falsely suggests a high PCWP–LV gradient.

A proper PCWP that is appropriately damped without a large V wave is usually a satisfactory substitute for LA pressure, with overesti- mation of the transmitral gradient by 1.7 ± 0.6 mmHg according to some investigators.⁵⁴

Note that patients with elevated LA pressure and ample V wave, such as patients with severe mitral regurgitation or HF, have an early diastolic pressure gradient between LA and LV, but in contrast to severe MS, LA and LV pressures equalize at mid-diastole (diastasis) and there is no LA–LV end-diastolic gradient.

While true MS may occur with MAC, MAC “MS” is often a misnomer, and the hemodynamics of MAC predominantly correspond to diastolic HF (+/- mild MS), more than true MS (Figure 6.13).⁵³

C. Echocardiographic Wilkins score

The Wilkins score is an assessment of the severity of the valvular and subvalvular distortion and a rough estimate of suitability for percutane- ous mitral valvuloplasty. It consists of the following four elements, each one being graded from 1 to 4:⁵⁵

valve thickness (only tips are thick vs. the whole valve is thickened)
valve mobility (only leaflet tips are immobile vs. tips and body vs. tips, body, and base are immobile)
valve calcification (spots of calcium vs. the whole leaflet is calcified)
chordal thickening and calcification (thickening only underneath the leaflets vs. thickening extends towards the papillary muscles).

A score ≤ 8 makes the valve appropriate for commissurotomy. An additional feature that determines suitability for commissurotomy is the presence of calcium at the commissures (Figure 6.10C). Commissural fusion is present in MS, but commissural calcium is only seen at a later stage and precludes successful commissurotomy, even if the Wilkins score is low. In general, Wilkins score is higher in patients older than 60–70 years of age.

Schematic illustration of two examples of mitral stenosis with a diastolic pressure gradient between PCWP and LV at a heart rate of 60 bpm (dark filled areas). — **Figure 6.11** Two examples of mitral stenosis with a diastolic pressure gradient between PCWP and LV at a heart rate of 60 bpm (*dark filled areas)*. Due to phase delay, the tracing of PCWP has been shifted to the left so that the *peak of the V wave almost intersects the LV downslope*. There is no LA–LV diastasis, i.e., LA pressure remains higher than LV pressure throughout diastole, signifying severe MS. *LA A wave is pronounced but LV A wave is reduced because of ventricular underfilling*. The lack of diastasis translates into a slow E downslope on echo, which does not return to the baseline.

**With more severe MS, the LA pressure tracing is higher and the intersection between V wave and LV occurs earlier;** *this translates into an opening mitral snap that is closer to S* ₂.

Schematic illustration of false impression of MS resulting from the use of PCWP as a surrogate for LA pressure in a patient with large V wave (severe MR, severe MAC). — **Figure 6.12** **False impression of MS resulting from the use of PCWP as a surrogate for LA pressure in a patient with large V wave (severe MR, severe MAC).** When LA–LV pressures are simultaneously recorded, an early diastolic gradient is seen between LA and LV and is quickly followed by diastasis. However, when PCWP–LV pressure recording is performed, the damped and prolonged Y descent creates the impression of a large pressure gradient and a lack of diastasis, even when PCWP is appropriately shifted to the left, thus creating the impression of MS. Even in true MS, PCWP overestimates the transmitral gradient if V wave is large/MR is present.

Note that LV A wave is still present and prominent, arguing against severe MS.

Reproduced with permission from Hanna EB. Mitral stenosis. In: Hanna EB, Glancy DL. Practical Cardiovascular Hemodynamics. New York, NY: Demos Medical, 2012, p. 101.

Schematic illustration of the difference between rheumatic MS and MAC-MS. — **Figure 6.13** **Illustration of the difference between rheumatic MS and MAC-MS.** In **MAC-MS**, LV and LA per se are “sick”, with a large V wave, reflective of poor LA compliance; and a high LVEDP, reflective of poor LV compliance. Also, there is AF in this case. LA pressure is high in both cases, but in MAC-MS, it is much more due to LV and LA disease than to valvular obstruction. As such, note the brisk LA y descent and the rapid equalization of LV and LA pressures on a longer RR interval, demonstrating the low valvular impedance in MAC MS. This corresponds to a steep E descent on mitral Doppler. Had PCWP been used here, the false impression of significant MS would have been exaggerated.

D. TEE

In general, TEE does not offer additional information regarding the severity and morphology of MS (Wilkins score). The apical TTE views “look” directly into the subvalvular apparatus and allow estimation of the subvalvular thickening better than TEE, which “looks” at the mitral valve through the enlarged LA.

However, TEE is indicated prior to percutaneous valvotomy, in order to assess: (i) severity of MR, and (ii) presence of left atrial appendage thrombus.

E. Stress testing and other maneuvers for MS

Resting transmitral gradient may not reflect the true severity of MS. As expressed in Gorlin’s equation, for the same mitral valve area, the transmitral gradient is directly proportional to the square of the per-second flow across the valve (MVA ≈ transmitral flow/√transmitral gradient). Thus, if the per-second diastolic flow doubles because the cardiac output increases and/or the diastolic filling time decreases (tachycardia), the pressure gradient across the valve quadruples.^56–58

Stress testing is useful in symptomatic patients with mild/moderate MS, after ruling out tachycardia or high-output state as an aggravating factor, and helps sort out whether their symptoms are due to MS or LV failure. In MS, PCWP and transmitral gradient increase with exercise while LV diastolic pressure remains unchanged; in LV failure, both PCWP and LV diastolic pressure increase with exercise while the gradient remains unchanged. MS is clinically significant and would likely benefit from an intervention if the mean transmitral gradient increases to >15 mmHg; or if systolic PA pressure or PCWP increases to >60 mmHg or >25 mmHg, respectively, without a significant increase in LVEDP.

A second condition where stress testing is helpful is asymptomatic severe MS. An exertional increase of systolic PA pressure to >60 mmHg or a severe increase in transmitral gradient signifies that the patient is likely limited functionally and will likely benefit from an intervention to avoid the consequences of prolonged pulmonary hypertension.

Note that, similarly to exercise, the heavy use of vasodilators increases cardiac output and the mitral gradient. Also, passive leg raising increases venous return and the mitral gradient. In fact, passive leg raising is routinely performed during echo assessment of MS. Dobutamine may also be used.

III. Treatment

A. Medical therapy

Diuretics and β-blockers often produce substantial symptomatic improvement. β-Blockers increase diastolic time, allowing more time for the slow LA emptying. A heart rate of 60 bpm should be targeted. Medical therapy is not usually indicated as a standalone therapy, as even patients with class II symptoms have impaired long-term outcomes without mechanical relief of MS. Standalone medical therapy may, however, be used in select patients with class II symptoms:
- Patients with class II symptoms who do not have appropriate morphological features for percutaneous mitral balloon valvotomy (PMBV). Class II symptoms are not severe enough to warrant surgery.
- Patients who improve after PMBV but have residual symptoms.
- Patients with mild/moderate MS that is symptomatic because of hemodynamic disturbances (tachycardia, high cardiac output).
- Sedentary, elderly patients with mild symptoms on exertion.⁵⁹ This includes MAC MS.
Treatment of AF: β-blockers and/or digoxin are used for rate control. Rhythm control may be attempted for a new AF, but repeated DC cardioversions should be avoided in light of the associated stroke risk and the fact that, over time, rhythm control is difficult to achieve in MS. The yearly risk of stroke with the AF–MS combination is 10–15%, implying a critical role of warfarin therapy.

B. Indications for percutaneous or surgical therapy

A mechanical intervention is indicated for select patients with severe (≤1.5 cm²) or very severe MS (≤1 cm²):^15–17

Symptoms class II–IV for PMBV or III–IV for MV surgery (class I indication).
Asymptomatic patient with moderate pulmonary hypertension qualifies for PMBV (systolic PA pressure >50 mmHg at rest, >60 mmHg with exertion) (class IIa). Pulmonary hypertension more readily indicates mechanical correction in MS than MR, as pulmonary hypertension of MS more quickly progresses to precapillary pulmonary hypertension and RV failure.
Asymptomatic patient with plans for pregnancy or major high-risk surgery qualifies for PMBV (ESC class IIa)
Asymptomatic patient with AF. PMBV may be performed, but the strength of this recommendation is weak (IIb), as PMBV has not been universally successful in preventing or reverting rheumatic AF (≠ MV repair for MR).⁵⁹

Also, as explained above, symptomatic patients with moderate MS (MVA 1.5–2 cm²) and moderate gradient at rest need to be assessed with stress testing. A severe increase in transmitral gradient (>15 mmHg) without a significant change in LVEDP implies that MS is hemodynamically significant and may benefit from PMBV (class IIb). On the other hand, patients with moderate anatomic MS who have a severe gradient at rest need to be invasively assessed and treated for associated hemodynamic disturbances: tachycardia, high-output state (e.g., anemia, vasodilator therapy). In the absence of those hemodynamic disturbances, moderate MS may be the cause of the severe gradient and the pulmonary hypertension and may warrant PMBV (also, a valve area of 1.6 cm² may imply severe MS when indexed for body size).

Schematic illustration of beta-blockers slow the heart rate and allow more LA emptying, which ultimately reduces LA pressure, V and A waves. — **Figure 6.14** β-blockers slow the heart rate and allow more LA emptying, which ultimately reduces LA pressure, V and A waves. The slope of the LA descent is unchanged (*arrow*s); however, a longer diastole allows a longer duration of emptying and approximation of LA and LV pressures. Diastasis may be achieved if MS is not very severe. The height of LA pressure ↓ after several long R–R cycles as LA volume ↓.

Reproduced with permission from Hanna EB. Mitral stenosis. In: Hanna EB, Glancy DL. Practical Cardiovascular Hemodynamics. New York, NY: Demos Medical, 2012, p. 107.

For patients who are not PMBV candidates, mitral valve replacement is not usually considered unless symptoms are class III/IV, i.e., more severe than required for PMBV, as valve replacement has a higher operative mortality than PMBV. Patients with class II symptoms and a valve morphology that is not favorable for PMBV generally undergo medical therapy with 6-month follow-ups rather than surgery. Yet, those patients with severe pulmonary hypertension are likely more symptomatic than they claim and qualify for valve replacement (class IIa in older guidelines).

On the other hand, patients with class III/IV symptoms and a valve morphology that is not optimal for PMBV who are at a high surgical risk may still undergo PMBV (class IIb).

C. Percutaneous commissurotomy (or percutaneous mitral balloon valvotomy [PMBV])

When feasible, PMBV is the therapy of choice for MS.

Mortality = 1–2%, stroke ~1%
Risk of severe MR ~2–5% (moderate MR ~15%)
A successful PMBV is defined as a post-PMBV valvular area ≥ 1.5 cm² with ≤ moderate (2+) MR⁶⁰
PMBV should be considered if:
1. Wilkins score ≤ 8 with no commissural calcium. The extent of calcifications and the subvalvular involvement are the two most impor- tant features of Wilkins score.
2. No MR, or mild MR.
3. No thrombus in the left atrium or left atrial appendage (ruled out by TEE). If thrombus is present, give 1–3 months of anticoagulation then reassess and attempt PMBV if the thrombus resolves. Surgical commissurotomy is an alternative.

Valvotomy works by splitting the fused commissures. Unlike AS, early MS mainly consists of a commissural fusion that is not calcified. Tearing this fusion opens the mitral orifice, and thus balloon valvotomy is effective in treating early MS. Once the fibrosis and the immobility extend to the body of the leaflets or the subvalvular apparatus, or once calcium develops, valvotomy becomes less effective and risks tearing the stiff unyielding valve or the subvalvular apparatus in the process of dilating the orifice. Also, the balloon may get stuck in the thick subvalvular apparatus and tear it upon inflation. This is how Wilkins score and commissural calcium predict outcomes with PMBV.

In its original description, a Wilkins score ≥ 12 particularly predicted poor results with PMBV, while over a third of patients with an intermediate Wilkins score of 9–11 had a good result with PMBV.In one large analysis, ~80% of patients with Wilkins score ≤ 8 and 56% of those with Wilkins scores 9–11 achieved a successful result with PMBV (>1.5 cm²), and even patients with Wilkins score ≥ 12 improved MVA, although a full success was uncommon (30%).⁶⁰ In an analysis of elderly patients >70 years of age, MVA and symptoms improved with PMBV in most patients, even those with Wilkins score >8; half of patients with Wilkins score >8 had improvement of MVA from 0.8 to >1.2 cm ², with functional class improvement.⁶¹ Also, while moderate 2+ MR predicts a 4× higher failure rate, it does not prohibit PMBV.^55,60 In the original Wilkins paper, no patient with moderate MR developed severe MR after PMBV.⁵⁵ In a large PMBV series, ~6.5% of patients had moderate baseline MR.⁶⁰ Balance Wilkins score with the degree of MR (Wilkins score of 10 without any MR may be as amenable to PMBV as Wilkins score of 8 with mild-to-moderate MR).

Thus, while a surgical approach is advisable in high scores, PMBV may still be beneficial in intermediate (9–11) or even high scores, or patients with 2+ moderate MR when the surgical risk is high.^60–62 Hence, ACC guidelines consider PMBV a reasonable therapy for patients with class III/IV symptoms and a valve morphology that is not favorable for PMBV if the surgical risk is high (class IIb indication).

After a successful PMBV, ~25% of patients require MV replacement within 5 years, whether for restenosis (10-25%), progression of a suboptimal result, or progression of MR; this risk is higher in patients with an unfavorable early result or a high Wilkins score (up to 50%).^60,63 Wilkins score is associated not only with short-term but also with long-term failure.^63,64 Redo PMBV may be performed with a high success rate (~75%) if favorable echocardiographic features are still present.⁶³

D. Surgical mitral commissurotomy

Perioperative mortality = 1–2%
Indications: pliable mitral leaflets with no severe subvalvular involvement, but with a left atrial appendage thrombus that precludes percutaneous therapy, CAD that necessitates CABG, or unavailability of percutaneous therapy. In general, for the same patient, surgical commissurotomy has the same success rate as PMBV.

E. Mitral valve replacement; AF procedures

MV replacement is necessary in the case of extensive mitral valve calcification, high Wilkins score, or combined MS and MR. The operative mortality is ~4–6%, which increases to ~12% if significant pulmonary hypertension has developed. Since MV replacement has a higher risk than PMBV, patients who do not qualify for PMBV qualify for MV replacement later in the course of the disease, i.e., for more severe symptoms (III–IV).

In a patient with persistent or symptomatic AF, biatrial ablation lines that include the pulmonary veins, the venae cavae, and the valvular annuli (maze procedure) may be performed during any cardiac surgery and are associated with a high success in maintaining sinus rhythm (up to 80%), even in patients with left atrial enlargement (ACC class IIa indication).⁶⁵ When radiofrequency is used instead of cutting and sewing, maze procedure may not significantly add to the complexity and risk of a mitral valve procedure as the LA is already open.¹⁵ A less invasive uniatrial or isolated pulmonary vein ablation (mini-maze) may be performed, with similar efficacy in one trial.⁶⁶ Excision of the LA appendage further reduces stroke risk on top of chronic anticoagulation (class IIa, LAAOS III trial). Anticoagulation is recommended for at least 3 months after AF ablation or LA appendage closure (class IIa).

Patients with severe MS and chronically elevated PCWP > 25 mmHg may develop reactive changes in the pulmonary arteriolar bed, severe increases in the pulmonary vascular resistance (PVR), as high as 25 Wood units, and very severe pulmonary arterial hypertension disproportionate to the PCWP. This may be associated with severe RV failure. Even at this stage, however, patients usually respond to correction of MS; the elimination of the passive postcapillary component of pulmonary hypertension results in an immediate drop in PA pressure, followed by a slow and gradual decline in the reactive and hypertrophic component.^67–69 In fact, PA pressure and PVR decline towards normal over the course of several weeks to months. Therefore, invasive treatment is still warranted at the stage of severe pulmonary hypertension. In the majority of patients, an almost complete normalization of pulmonary hypertension is expected. Pulmonary vasodilators (endothelin antagonist, intravenous prostacyclin) may be temporarily used in the early postoperative period.

3. AORTIC INSUFFICIENCY

I. Etiology

A. Acute AI

Endocarditis: the vegetation may perforate the leaflet(s) or prevent valvular coaptation.
Aortic dissection leads to AI through three potential mechanisms: (i) dilatation of the sinotubular junction; (ii) dissection extends into the leaflet attachment at the sinotubular junction, resulting in leaflet prolapse and eccentric AI; (iii) dissection flap prolapses through the aortic orifice and prevents leaflet coaptation. AI may also be pre-existent, secondary to a bicuspid aortic valve.
Closed chest trauma may lacerate the aortic leaflet or its sinotubular insertion, causing it to prolapse. Being anterior, the aortic valve is the valve most commonly involved in chest trauma.

B. Chronic AI

Dilatation of the ascending aorta with secondary AI: this is the most common cause of severe AI. Dilatation of the ascending aorta may lead to dilatation of the junction between the tubular aorta and the sinuses of Valsalva, called the sinotubular junction, precluding the coaptation of the aortic leaflets (Figure 6.15). Aortic dilatation is a primary process that can cause AI or coexist with bicuspid aortic valve disease. While potentially causing AI, aortic dilatation may reciprocally be induced or worsened by the high stroke volume of AI; it is also worsened by the high post-stenotic jet of AS (post-stenotic dilatation).

Causes of ascending aortic disorders:
1. Degenerative aortic dilatation, related to age and HTN, is the most common cause of ascending aortic dilatation.
2. Cystic medial necrosis, which occurs in younger patients: (1) Marfan or Marfan fruste, (2) bicuspid aortic valve, (3) spondyloarthropathies.
Aortic valve disorders
1. Bicuspid aortic valve is the most common valvular cause of severe AI. AI results from prolapse of a leaflet or incomplete closure of a thickened redundant valve.
  
  Figure 6.15 Aortic leaflets and their relation to the ascending aorta. A normal valve apparatus consists of aortic tissue that extends from the sinotubular junction, forms local aortic dilatations called aortic root or sinuses of Valsalva (S), then touches the ventricle and suspends the aortic leaflets (L) (also called semilunar cusps). The sinuses of Valsalva are an extension of the aortic wall tissue. The sinotubular junction, rich in elastic tissue, provides the main support for the sinuses. Two-thirds of the circumference of the aortic valve is connected to the muscular ventricular septum anteriorly, while the posterior one-third is in fibrous continuity with the anterior mitral leaflet (fibrous trigone, close to the non-coronary posterior cusp) (see Figure 6.1). At one point posteriorly, the aortic valve is in continuity with the interatrial septum. The annulus is a ring formed by the junction of the basal valvular hinges (leaflets’ insertion on the ventricle). The coronary arteries originate from the sinuses of Valsalva (upper portion).
2. Old, healed endocarditis. Subacute endocarditis may only be associated with mild or moderate AI early on, but progressive valvular deformity results from the healing process and leads to progressive AI (progressive widening of a perforation or progressive retraction and malcoaptation of the scarred leaflet(s)).
3. Idiopathic valvular degeneration with increased and disorganized collagen and elastic fibers. Anatomically, a mild degree of thickening/retraction, redundancy, or myxomatous degeneration is seen. This was the most common cause of isolated AI in one study.⁷⁰
4. Rheumatic fever with fibrosis and retraction of the leaflets. Fibrosis and fusion of the commissures also leads to AS. The aortic valve is immobile and does not open or close (combined AS/AI).
5. Prolapse of an aortic valve leaflet in the context of bicuspid aortic valve, endocarditis, trauma, or myxomatous degeneration.
6. Degeneration of a bioprosthesis.

II. Pathophysiology and hemodynamics (Figure 6.16)

A. Acute AI

In acute AI, LV is non-compliant and LV volume is normal. Thus, the regurgitant volume leads to a severe increase in LVEDP and the aortic and LV diastolic pressures come close together (Figure 6.12). LV diastolic pressure exceeds LA pressure in mid- or late-diastole (Figure 6.12), leading to a reverse LV–LA gradient and forcing the mitral valve to close prematurely (functional MS), a finding typical of decompensated AI.^71,72 Since LV is not dilated, the stroke volume is reduced in acute AI. Therefore, in addition to the low DBP, SBP is usually low (e.g., BP 90/40 mmHg). As opposed to chronic AI, pulse pressure is only mildly widened, but this already suggests acute AI in a patient with acute heart failure, wherein the arterial pulse pressure is typically narrow. Tachycardia is an important compensatory response in acute AI as it increases the cardiac output and reduces the regurgitant time, and thus should be respected.

B. Chronic compensated AI

In chronic compensated AI, LV volume increases, the total stroke volume increases, leading to a high pulse pressure (e.g., 160/60 mmHg), and the forward stroke volume is maintained. The LV is large and compliant in a way that it accommodates the regurgitant volume without an increase in LVEDP. The aortic and LV pressures do not approximate at the end of diastole; on Doppler, this corresponds to a gradual rather than steep drop of the regurgitant flow velocity with a pressure half-time that is >250 ms, even if AI is severe. While a wide pulse pressure (>½ SBP or >60–80 mmHg) is a very sensitive finding in chronic severe AI, it is not a specific finding and may be seen in a poorly compliant aorta and in high-output states with low afterload (patent ductus arteriosus, hyperthyroidism, anemia, fever, and arteriovenous fistula).

The peripheral femoral pressure may get excessively amplified and exceed the central systolic pressure by >50 mmHg. This is an exaggeration of a normal effect and is due to the large initial stroke volume percussing the less compliant, muscular peripheral arteries. This large percussion is followed by aftershock waves that get reflected in the periphery and cause a second systolic pressure peak (pulsus bisferiens).

C. Chronic decompensated AI

In chronic decompensated AI, LV function starts to decline, and EF decreases such that the forward stroke volume declines and the LV volume further increases. LV compliance starts deteriorating and LVEDP rises, only with exercise initially. Similarly to acute AI, LV and aortic pressures approximate in end-diastole.^71,72 On Doppler, this corresponds to a steep drop of regurgitant flow velocity throughout diastole with a short pressure half-time <250 ms. Total stroke volume remains elevated, and thus the pulse pressure remains elevated. At an advanced stage, when EF is severely reduced, total stroke volume and pulse pressure may decline.

As opposed to other valvular disorders, chronic AI is well tolerated during exercise. In fact, tachycardia reduces diastole and the time available for regurgitation, and the vasodilatation associated with exercise reduces the regurgitant volume, which allows an increase in cardiac output during exercise. That is why severe AI, as opposed to MR, is well tolerated for years before symptoms develop. In addition, in AI, volume overload must surpass the compliance of the LV then the compliance of the LA to provoke pulmonary edema, whereas in MR only surpassing the compliance of the LA is necessary. Symptoms develop very gradually and the patient adapts to them over the years, sometimes not realizing the change in functional status.

Note that both preload and afterload are increased in severe AI. Afterload= wall stress= LV systolic pressure x radius/(2x LV thickness). Thus, afterload is proportional to both LV systolic pressure and LV radius and dramatically rises with LV dilatation. Eccentric LV hypertrophy allows the LV to adapt to this load increase up to a certain point, beyond which the LV succumbs to afterload. The initial decline in EF is the result of a progressive increase in LV size and afterload rather than an intrinsic LV contractile dysfunction (afterload mismatch). This process is fully reversible with AVR and is different from the early EF decline in MR, which already implies a significant contractile dysfunction that may be irreversible, LV afterload being reduced with MR early on. With time, however, even in AI, impaired contractility progressively becomes a major contributor to the decline in EF and may not be fully reversed with surgery, particularly when EF is < 25% or the decline has persisted over 18 months preoperatively.

III. Diagnosis

A. TTE

TTE is useful to diagnose the severity and etiology of AI. The following features suggest severe AI:

The narrowest AI neck, measured at the aortic valve level and called vena contracta, is >6 mm (long-axis view). The width of the regurgitant jet just below the vena contracta is >60% of the LVOT diameter (long-axis view), or >60% of the LVOT area (short-axis view), at a Nyquist limit of 50-60 cm/s. Eccentric jets may be underestimated as the color jet abuts the mitral valve or the septum and shrinks in color speed.

Figure 6.16 1. In acute AI, LV volume is normal and the regurgitant volume leads to a severe increase in LVEDP. The LV and aortic pressures approximate in end-diastole forming a diastolic triangle (blue arrows) (∆<30 mmHg or <25% of SBP). LV diastolic pressure exceeds LA pressure in mid or late diastole (gray arrow).

2. In chronic AI, LV volume increases and the total stroke volume increases, thus leading to a high pulse pressure, and the forward stroke volume is maintained. The LV is large and compliant in a way that it accommodates the regurgitant volume without an increase in LVEDP.

3. In chronic decompensated AI, the LV function starts to be impaired, EF is reduced in a way that the forward stroke volume is reduced, and the LV volume increases, leading to increased LVEDP. Total stroke volume remains elevated, and thus, the pulse pressure remains elevated. Note the attenuation or loss of the dicrotic notch, especially in acute AI. In chronic AI, the aorta may improve its compliance, causing the dicrotic notch to re-emerge. EDV, end-diastolic volume; EF, ejection fraction; ESV, end-systolic volume; RgV, regurgitant volume; SV, stroke volume.

Reproduced with permission from Hanna EB. Aortic regurgitation. In: Hanna EB, Glancy DL. Practical Cardiovascular Hemodynamics. New York, NY: Demos Medical, 2012, p. 115.
Holodiastolic flow reversal in the descending aorta (most important feature).
On the spectral Doppler, pressure half-time of the regurgitant flow is <250 ms; this correlates with AI acuity and the status of the LV. Pressure half-time may be 250-400 ms if AI is severe but chronic and compensated. Conversely, pressure half-time may be <250 ms in patients with moderate AI but underlying severe LV dysfunction (from CAD or HTN).
Also, to diagnose chronic severe AI, LV must be dilated. Yet the diagnosis should not rely on pronounced LV dilatation; symptoms frequently develop in patients with only mild LV dilatation (LVESD 20+/-4 mm/m²).⁷³

B. TEE and cardiac MRI

TEE is not significantly superior to TTE for the assessment of the severity of AI. TEE is superior for the anatomical assessment of the aortic valve and aortic annulus (bicuspid morphology, endocarditis), and for the assessment of the ascending aorta.

Cardiac MRI is the best non-invasive modality for assessing AI, via quantifying antegrade and retrograde aortic volumes, or the difference between LV and RV stroke volumes. It is valuable when AI severity is unclear by echo. It is also valuable in MR.

C. Invasive assessment (aortic root angiography and hemodynamic measurements)

As in other valvular disorders, invasive assessment of AI is indicated when echo is inconclusive regarding the severity of AI or when there is discrepancy between clinical findings and echo results.

On aortic root angiography, severe AI is characterized by LV filling that is as dense (3+) or denser (4+) than aortic filling. Hemodynamically, severe AI is characterized by four features (Figures 6.16 and 36.18): (1) wide aortic pulse pressure, particularly seen in chronic AI; (2) loss of the aortic dicrotic notch, particularly seen in acute AI; (3) LV end-diastolic pressure approximates aortic pressure; (4) LV end-diastolic pressure exceeds mean PCWP and even end-diastolic PCWP (the last two findings are seen in acute or decompensated AI).

IV. Natural history and symptoms

Asymptomatic severe AI with normal LV function has a slow progression: <0.2% sudden cardiac death per year, 4.5% progression to symp- toms and/or LV dysfunction per year.¹⁵ Class II dyspnea develops slowly and insidiously and may be overlooked. Patients with LVESD >50 mm or LVEDD >70 mm have the highest risk of progression to symptoms and/or LV dysfunction (10–20% per year).

Conversely, symptomatic AI or AI with LV dysfunction has a mean survival rate of ~3 years without surgical intervention: yearly mortality 5–10% if NYHA class II dyspnea, >10% if angina, >20% if class III–IV HF, wherein the mean survival is 1.5 years.⁷⁴

AI symptoms appear late in the disease process, usually after LV has enlarged. Fortunately, unlike MR, LV enlargement and dysfunction do not necessarily indicate intrinsic damage and are partly due to afterload mismatch. Class II dyspnea appears earlier than angina and severe HF. Subendocardial coronary flow being driven by the perfusion pressure gradient between aortic diastolic pressure and LVEDP, angina is often functional and related to the severe drop in aortic diastolic pressure and the increase in LVEDP. Moreover, O₂ demands of the large LV are severely increased. Angina may be nocturnal rather than exertional, aggravated by bradycardia, wherein the aortic diastolic pressure decreases to very low levels. Diastolic reversal of coronary flow may be seen in severe cases. Palpitations may appear early on and are related to the ejection of a large LV volume, especially after a PVC; they are not, per se, an indication for surgical correction.

V. Treatment

A. Medical therapy

Aortic valve surgery is the only effective therapy for severe AI that requires treatment. Vasodilators (ACE-I, CCBs) are useful for systolic HTN. Systolic HTN is inherent to severe AI and may prove difficult to control, particularly that reducing SBP may come at the price of a harmful drop of DBP and myocardial ischemia: β-blockers decrease DBP, while ACE-I, by reducing AI volume, may not adversely reduce DBP. Vasodilators may also be used in patients who are not undergoing surgery because of high risk (class IIa). By prolonging diastole, β-blockers may aggravate symptoms and DBP, but if tolerated, they may prevent the deleterious LV dilatation and remodeling in non-surgical cases, per retrospective analyses.

In severe asymptomatic AI with mildly dilated LV and no indication for surgery, vasodilators may slow LV dilatation; however, a randomized trial has disproved this theory, and thus vasodilators are not routinely recommended in severe asymptomatic AI.⁷⁵ Mild exercise is allowed in asymptomatic severe AI. Athletic activity may be allowed in some cases, after performing stress testing for safety purposes; the long-term effect of exercise on severe AI is, however, unknown.

B. Indications for surgery

Aortic valve surgery is indicated for severe AI with any of the following:^15,17

Symptoms (NYHA functional class ≥ II)
EF ≤55% (as compared to EF ≤ 60% for MR)
LVESD >50 mm (as compared to ≥ 40 mm for MR) or >25 mm/m² of BSA
Asymptomatic severe AI while undergoing CABG or other cardiac/aortic surgery. AVR is also reasonable for moderate AI while undergoing cardiac/aortic surgery (class IIa indication).
LVEDD correlates with AI volume overload but less strongly with LV systolic function (unlike LVESD). Surgery is considered for LVEDD >65 mm, particularly when LV dilatation is rapidly progressive and the surgical risk is low (class IIb). Surgery is also considered for EF of 55-60%, when there is evidence of progressive EF decline (class IIb)

In modern registries, symptoms (particularly class II) occur earlier and more frequently than pronounced LV enlargement; ~85% of symptomatic, operated patients had LVESD and LVEDD below surgical cutpoints. This is particularly true in older patients with stiff LV that does not dilate and accommodate the AI volume overload, thus raising LVEDP early on.⁷³ The less LV can dilate, the earlier symptoms develop. Furthermore, modern data suggests that indexed LVESD ≥20 mm/m², rather than 25 mm/m², is a strong predictor of AI mortality and surgical benefit and may be a better cutpoint for surgical referral.⁷³ At the very least, asymptomatic patients with less severely enlarged LV (LVESD 40–50 mm or LVEDD 55–65 mm) should be re-evaluated by echo in 3 months then every 6–12 months if the LV dimensions are stable. If unstable, echo should be repeated every 3 months.

AI is tolerated for a long period of time before symptoms develop. Even when symptoms develop, they are insidious in a way that the patient may not realize his functional limitation. Before considering AI asymptomatic, exercise testing is often warranted.

Patients with advanced symptoms or LV dysfunction- As opposed to MR, LV function does not usually deteriorate postoperatively and is likely to improve even with markedly reduced EF.⁷⁶ Early on in AI, the reduced EF is secondary to the high afterload rather than intrinsic dysfunction (afterload mismatch). AVR reduces regurgitant flow, which reduces LV wall stress/afterload and allows an improvement of EF, the earliest sign being a reduction of LV size. However, long-term postoperative survival is significantly reduced, ~ in half, in patients with NYHA class III–IV symptoms or EF <50% preoperatively, especially if LV dysfunction has been prolonged >18 months, severe (EF <25%), or not recovering early postoperatively (long-term mortality 5–10% per year).^74,77,78 Patients with EF <25% may have irreversible myocardial damage and persistent LV dysfunction postoperatively, yet most of these patients have a meaningful postoperative recovery, particularly if LV dysfunction is recent and if HF significantly improves with preoperative diuretics and vasodilators.^15,76 No EF cutoff is prohibitive of AVR. Postoperatively, the earliest sign of LV improvement is a decrease in LV diastolic size, which should occur within 2 weeks of surgery. In fact, 80% of LVEDD decline occurs within 2 weeks, and correlates with the eventual improvement of EF that ensues within 6–12 months.¹⁵ A lack of early reduction of LV size implies intrinsic LV dysfunction.

C. AI and ascending aortic dilatation

Ascending aortic replacement is indicated for: (i) ascending aortic dilatation, ≥ 5.5 cm in most patients, including bicuspid valve patients, or ≥ 5 cm in patients with Marfan syndrome or bicuspid valve with family history of aortic dissection; or (ii) ascending aortic dilatation ≥ 0.5 cm/ year. The same 5.5 cm cutoff is used for aortic dilatation at the level of the sinuses of Valsalva or beyond the sinotubular junction. When dilatation extends to the sinuses, the ascending aorta is replaced with an aortic graft that is sutured to the aortic ring, and the valve is spared if no AI (valve-sparing aortic root replacement or reimplantation technique [David’s surgery]); the coronaries are reimplanted, sometimes with an interposition graft.^79–81

Patients with combined severe ascending aortic disease and moderate or severe AI may undergo a composite graft replacement of both the aortic root and the aortic valve (Bentall procedure, or Cabrol procedure if an interposition graft is used for coronary reimplantation). The composite graft typically has a mechanical valve, but biological composite grafts are available. The valve may be spared and reimplanted rather than replaced if the cusp’s tissue quality is good and the valve is not calcified or severely deformed, this being associated with an acceptable long-term result and a 5–15% risk of reoperation for AI at 10 years.^79–81 Even a bicuspid valve may be repaired if non-calcified and regurgitant rather than stenotic, sometimes along with resuspension of a prolapsed cusp (class Ilb).

Regarding patients with moderate ascending aortic dilatation along with severe AI or AS: beside aortic valve replacement, replace the ascending aorta when it is ≥ 4.5 cm rather than 5.5 cm (class IIa). If unoperated, ~60% of patients with a bicuspid valve and an aorta of 4.5–4.9 cm go on to develop significant aortic events requiring aortic surgery over the next 15 years, mainly progressive aortic dilatation;⁸¹ thus, in this range, concomitant aortic surgery is particularly applied to young patients and those at a low operative risk.

D. Aortic valve repair

Aortic valve reimplantation, a form of aortic valve repair, may be performed in patients with severe or moderate AI whose primary disorder is aortic root disease and whose cusp tissue quality is good. Resuspension of a prolapsed cusp may additionally be performed.

While aortic valve replacement remains the standard surgery for AI due to aortic valve disease, aortic valve repair may be performed for a minority of cases, such as prolapse of an elongated, non-calcified leaflet (cusp resuspension with resection or plication of the edge) or leaflet perforation from healed endocarditis (patch repair). The prolapsed valve is commonly bicuspid, wherein the conjoint cusp elongates and prolapses; this cusp is re-suspended and the raphe of the conjoint cusp resected. Since annular dilatation is common in these patients, subcommissural annuloplasty is often performed.

4. AORTIC STENOSIS

I. Etiology

A. Age-related calcific degeneration

This is the most common cause of AS. It is related to endothelial valvular injury from atherosclerotic risk factors and hemodynamic stress, like MAC. Calcifications develop throughout the valve leaflets rather than specifically over the commissures. Non-stenotic aortic valve sclerosis (thickening) precedes AS, is present in ~20% of patients older than 65 years, is associated with an increased risk of cardiovascular death and CAD, and progresses to some degree of AS in ~10% of patients at 5 years.

B. Bicuspid aortic valve

Bicuspid aortic valve is the most common congenital heart disease (~1.3% of the population). It is present in >50% of patients with aortic coarctation and ~10% of women with Turner syndrome. It has a familial trend (10% bicuspid valve prevalence and 30% aortic dilatation in first-degree relatives) and is more prevalent in men (3:1).82 Screening of the patient’s children is appropriate.
Two of the three cusps are fused, most commonly the right and left cusps (80%), followed by the right and non-coronary cusps (20%). A residual raphe is often seen at the fusion site (Figure 6.17). A pliable bicuspid valve does not usually impede aortic flow, per se. However, the presence of two rather than three leaflets leads to a smaller surface in contact with the high-pressure stroke volume and marked leaflet bending, making the bicuspid valve more susceptible to shear stress. Progressive stress leads to calcific degeneration and AS later in life. The more asymmetrical the cusps are, the higher the stress is, and the faster AS develops.
Yet bicuspid valves may be stenotic at birth, in childhood, or in early adulthood, before calcium develops, when a significant degree of commissural fusion is present or when the valve is, in fact, unicuspid. This early AS may be treated with valvuloplasty.

Figure 6.17 (a) Difference in aortic orifice shape between the tricuspid and bicuspid aortic valves (short-axis view). Bicuspid valves are in fact “bicommissural” valves, while unicuspid valves are “unicommissural” or “acommissural” valves. The commissures of a bicuspid valve (arc) may be partially fused, leading to AS at an early age; otherwise, AS develops later in life. Note that aortic opening/closure becomes eccentric in bicuspid valves; this is seen on M-mode analysis of the aortic valve. On echo, instead of analyzing how many cusps are seen when the valve is closed, it is best to analyze how the aortic valve opens: an elliptical rather than a triangular opening is a hint to a bicuspid valve. RCC and LCC are often fused, NCC being the cusp looking towards the IAS. (b) Doming of the bicuspid aortic valve on a long-axis view.

IAS, interatrial septum; LCC, left coronary cusp; NCC, non-coronary cusp; RCC, right coronary cusp.
Later on, in early adult life between the ages of 20 and 50 years, 20% of bicuspid valves develop AI.⁸³ The remaining patients develop progressive aortic calcification and stenosis over time, as the bicuspid valve is more prone to mechanical and shear stress than a tricuspid valve. Severe AS usually appears in patients >40 years old, and 75% of bicuspid patients eventually develop severe AS over their lifetime.^83,84 Bicuspid aortic valve is the most common cause of AS in patients <70 years old (~two-thirds of AS), more so if <60 years old. In patients older than 70 years, bicuspid AS is the cause of 40% of severe AS.⁸³
While AS is the most common result of a bicuspid valve, severe AI or the combination of AI/AS is also possible. AI, which often develops at a younger age than AS, may be related to a dilated aortic root, but also to: prolapse of the asymmetrically large cusp (can’t support the extra weight of blood in diastole), myxoid thickening with malcoaptation, retraction of a fibrotic/calcified leaflet, or endocarditis.
Patients with a bicuspid aortic valve have a high risk of ascending aortic dilatation or dissection. Aortic dilatation >3.7 cm occurs in 50–60% of patients with bicuspid aortic valve by the age of 30, and occurs as frequently in young patients with a normally functioning aortic valve as in patients with aortic stenosis, regurgitation, or AVR.⁸⁵ This aortopathy is mainly secondary to cystic medial necrosis and is partly exaggerated by AS’s post-stenotic high velocity or AI’s volume and pressure load. Unlike the ascending aortic dilatation that is seen with age and HTN, this aortopathy frequently involves the aortic sinuses beside the tubular aorta; yet tubular aorta remains more involved 64% of the time. Patients with bicuspid valve should undergo, at least once, a screening with CT to assess the whole aorta. If dilatation is found to predominantly involve the sinuses, sinotubular junction, or early tubular aorta, TTE is usually appropriate for surveillance. A surveillance echo is recommended every year in patients with aortic size >4 cm at the sinuses or higher, and every 2 years in bicuspid patients with aortic size <4 cm. The lifetime risk of aortic dissection in bicuspid patients is ~3–6%, vs. 40% in Marfan patients. Dissection is often preceded by aortic dilatation, sometimes mild,⁸⁵ and in general, ~60% of all dissections occur at a diameter <5.5 cm.

C. Rheumatic fever (rare): in this case, AS almost always occurs with rheumatic involvement of the mitral valve and is often associated with severe AI.

II. Echo and catheterization diagnosis, pitfalls, and hemodynamics

The diagnosis of severe AS is often made by TTE (Table 6.2). An invasive hemodynamic study is only indicated when the physical exam sug- gests severe AS (absent A₂, pulsus parvus and tardus), yet the echocardiogram suggests a milder degree of AS or vice versa; or when the echocardiography data is inconclusive (for example, the valve area is ≤1 cm² but the gradient is low).

Table 6.2 Classification of AS severity.

	Mean transaortic gradient	Peak aortic velocity	Aortic valve area
Mild AS	<20 mmHg	2–2.9 m/s	>1.5 cm²
Moderate AS	20–40 mmHg	3–3.9 m/s	1–1.5 cm²
Severe AS	≥40 mmHg 60 mmHg for very severe	≥4 m/s 5 m/s for very severe	≤1 cm² or indexed area ≤ 0.6 cm²/m² (more specific if ≤ 0.8 cm2)

A. Echo and Doppler features of severe AS

Aortic valve velocity, which translates into transaortic pressure gradient (4 × velocity²), is the most important diagnostic feature of severe AS. However, Doppler may underestimate the pressure gradient if the cursor is not perfectly aligned with the transaortic flow. Therefore, the aortic velocity must be assessed in multiple views: the apical five- and three-chamber views, but also the suprasternal view and a special right parasternal view, wherein the transducer is aligned with the ascending aorta to the right of the sternum (a special pencil probe, Pedof, allows easier right parasternal access between the ribs and has a high signal-to-noise ratio). If only apical windows are used, the gradient is underestimated in 20% of cases.

Note that the transaortic gradient is difficult to assess by TEE because only one view is aligned with the aortic flow, the transgastric 5-chamber view, a view that is not always obtainable, hence the limited value of TEE in AS.

Aortic valve area (AVA) is calculated using the continuity equation and is subject to the additional pitfalls of measuring the LVOT diam- eter and velocity: AVA=LVOT area x (LVOT velocity/aortic valve velocity). Echocardiographic AVA measurement is even less accurate and reproducible than the transaortic gradient. LVOT is elliptical, and its anteroposterior diameter (long-axis view) is smaller than the septal-lateral diameter (Figure 6.18). Thus, the assumption of a circular LVOT underestimates the LVOT area and subsequently the AVA (by approximately 0.2 cm² on average).^86–88 LVOT area may be measured by planimetry using CT, 3D TEE or 3D TTE (if good transthoracic echogenicity), then AVA calculated via continuity Doppler equation. This is the hybrid method of AVA calculation, which has one caveat: surgical AVA cutoff of 1 cm² is not well validated with the hybrid method, and some studies suggest a better prognostic value of 1.2 cm² with this method.⁸⁹

Tags: Practical Cardiovascular Medicine

Nov 27, 2022 | Posted by admin in CARDIOLOGY | Comments Off

Thoracic Key

Fastest Thoracic Insight Engine

Valvular Disorders

1. MITRAL REGURGITATION

I. Mechanisms of mitral regurgitation

II. Specifics of various causes of mitral regurgitation

A. Acute MR

B. Degenerative mitral valve disease or mitral valve prolapse (MVP)

C. Functional ischemic MR and functional non-ischemic MR (Figures 6.4, 6.5)

D. Atrial functional MR

E. Rheumatic fever

F. Other causes of MR

III. Assessment of MR severity

A. TTE (see also Chapter 32: Figures 32.24–27, and Table 32.1)

B. TEE or cardiac MRI for indeterminate MR

C. Left ventriculography

D. Right heart catheterization

E. Stress testing and BNP

IV. Natural history and pathophysiology of organic MR

V. Treatment of organic (primary) MR

A. Surgical indications in primary MR

C. Medical therapy

VI. Treatment of secondary MR (ischemic and non-ischemic functional MR)

A. What is the primary driver of HF (MR vs. underlying LV failure)?

B. Will revascularization alone reverse MR?

C. Can MR therapy reverse the underlying tethering process?

D. Guidelines for the management of ischemic or non-ischemic functional MR

VII. Treatment of acute severe MR related to acute MI

VIII. Percutaneous mitral valve repair using the Mitraclip device (transcatheter edge-to-edge repair)

2. MITRAL STENOSIS

I. Etiology and natural history

II. Diagnosis (Table 6.1)

A. Echocardiographic features (see also Chapter 32)

B. Catheterization

C. Echocardiographic Wilkins score

D. TEE

E. Stress testing and other maneuvers for MS

III. Treatment

A. Medical therapy

B. Indications for percutaneous or surgical therapy

C. Percutaneous commissurotomy (or percutaneous mitral balloon valvotomy [PMBV])

D. Surgical mitral commissurotomy

E. Mitral valve replacement; AF procedures

3. AORTIC INSUFFICIENCY

I. Etiology

A. Acute AI

B. Chronic AI

II. Pathophysiology and hemodynamics (Figure 6.16)

A. Acute AI

B. Chronic compensated AI

C. Chronic decompensated AI

III. Diagnosis

A. TTE

B. TEE and cardiac MRI

C. Invasive assessment (aortic root angiography and hemodynamic measurements)

IV. Natural history and symptoms

V. Treatment

A. Medical therapy

B. Indications for surgery

C. AI and ascending aortic dilatation

D. Aortic valve repair

4. AORTIC STENOSIS

I. Etiology

A. Age-related calcific degeneration

B. Bicuspid aortic valve

II. Echo and catheterization diagnosis, pitfalls, and hemodynamics

A. Echo and Doppler features of severe AS

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