Diagnosis and Management of Mitral Valve Disease in the Elderly

Abstract

Calcific mitral stenosis, commonly seen in the elderly in developed countries, occurs primarily due to mitral annular calcification, and its prevalence is increasing secondary to an aging population. Mitral regurgitation, commonly seen across all age groups, occurs primarily due to anatomical or functional impairment of one or more components of the mitral apparatus or the left ventricle that are necessary for normal valve function, and its prevalence is increasing secondary to an increasing number of patients with heart failure. The current review discusses the diagnosis of and treatment options (medical, surgical, and transcatheter) for mitral valve disease, including the associated challenges, specifically in the elderly.

Although aortic stenosis is the most common cause of valve surgery or intervention in the elderly, mitral valve (MV) disease is common and ranks next. The cause of the disease in the elderly is usually different from the young. In addition, because of multiple comorbidities, the risk of surgery in the elderly is high in terms of both morbidity and mortality. However, development of catheter-based therapies has allowed this risk to be decreased and may address some of the mitral valvular issues encountered in the elderly.

In this paper, we review some of the common and unique MV diseases encountered in the elderly and their management approaches. We shall discuss calcific mitral stenosis (MS), mitral regurgitation (MR) of varied causes, endocarditis, prosthetic valve dysfunction, and contribution of MV disorders to the overall clinical picture in patients with multivalvular disorders ( Table 1 ). We will also discuss the value of a heart team approach and the role of prehab and rehab when a valvular intervention is contemplated ( Table 2 ).

Table 1. Common mitral valve disorders in the elderly.

Mitral valve stenosis
	Mitral annular calcification
	Infective endocarditis
	Radiation-induced
	Congenital
		Cor triatriatum
		Parachute mitral valve
		Double-orifice mitral valve
		Supravalvular mitral ring
	Functional
		Atrial myxoma
		Infected vegetation
Mitral valve regurgitation
	Primary
		Mitral valve prolapse
		Papillary muscle rupture
		Flail mitral valve
		Mitral annular calcification
		Infective endocarditis
	Secondary
		Ischemic
		Nonischemic
Prosthetic mitral valve dysfunction
	Prosthetic valve thrombosis
	Bioprosthetic valve stenosis and regurgitation
	Paravalvular leaks
	Infective endocarditis
As part of multivalvular disease

Table 2. Considerations when treating mitral valve disease in the elderly.

Patient considerations
	Anatomical feasibility of surgical vs. transcatheter approach
	Medical optimization
		Coronary artery disease
		Diabetes mellitus
		Hypertension
	Functional optimization
Heart team considerations
	Approach
		Transcatheter
		Surgical
	Intervention
		Repair
		Replace
	Risk
Miscellaneous considerations
	Prehabilitation
	Rehabilitation

Mitral Stenosis

MS is a common disease that causes substantial morbidity worldwide. ¹ The most common cause of MS worldwide is rheumatic heart disease. In contrast, in developed countries, the most common cause of MS, which has a prevalence of 0.02 to 2.00%, is mitral annular calcification (MAC). ² Epidemiologically, in high-income countries, the frequency of MAC-related MS increases with age.

As MS worsens, left atrium (LA) pressure increases, eventually leading to group 2 pulmonary hypertension and subsequently to right ventricular pressure overload, right ventricular dilation, and tricuspid regurgitation, giving rise to exertional dyspnea.

Rheumatic Mitral Stenosis versus Mitral Annular Calcification-Related Mitral Stenosis

Rheumatic MS is characterized by commissural fusion, with the greatest narrowing at the leaflet tips, resulting in a funnel-shaped stenosis ( Fig. 1A ). Consequently, the mitral leaflets truly impede LA emptying, which is reflected by a blunted LA y descent and persistent diastolic separation of LA and left ventricular (LV) pressures.

Fig. 1.

Primary types of MS. ( A ) Moderate MS due to rheumatic heart disease characterized by thickened leaflets with AML doming and bicommissural fusion. ( B ) Moderate MS due to severe MAC. AML, anterior mitral leaflet; LA, left atrium; LV, left ventricle; MAC, mitral annular calcification; MS, mitral stenosis; PML, posterior mitral valve; RA, right atrium; RV, right ventricle.

In contrast, MAC-related MS is characterized by annular and leaflet base calcification, resulting in narrowing at the annulus that progresses from an outward to inward manner, thereby allowing for relatively unrestricted leaflet tip motion ( Fig. 1B ). ³ Accordingly, the mitral leaflets minimally impede LA emptying. However, the LA v wave is unusually high and the LA y descent is unusually rapid and coupled with rapid equilibration of the LA–LV pressure gradient, thus implying an elevation of the transmitral pressure gradient (TMPG) to factors other than inflow obstruction. The progression of MAC-related MS is variable, ranging from an average increase in mean TMPG of 2.0 to up to 9.0 mm Hg/y. ⁴

Mitral Annular Calcification-Related Mitral Stenosis

MAC is commonly found incidentally in asymptomatic elderly patients. Prevalence estimates typically range from 8 to 15% in the general population to up ≥40% in the elderly population. Although significant valvular dysfunction directly related to MAC occurs in only 8 to 16% of MAC patients, it is the dominant etiology of MV stenosis in Western populations and is itself associated with worse prognosis. ^{5 6} Unfortunately, data regarding MAC-related MV dysfunction are limited, and significant challenges exist in the diagnostic and therapeutic approach to these patients, ranging from limitations of conventional echocardiographic assessment to ongoing controversy regarding clinical benefit of surgical or percutaneous treatment options in this high-risk population.

MAC-related MS, initially predominantly involving the posterior annulus and overtime extending to the anterior leaflet (particularly A2), can be characterized by four primary pathophysiological processes—tubular valve geometry, decreased inflow orifice area, reduced diastolic annulus expansion, and restricted leaflet opening. ⁷

Diagnosis of Mitral Annular Calcification-Related Mitral Stenosis

The primary accepted measurements for diagnosing and staging MAC-related MS are mitral valve area (MVA) and TMPG. Both values can be obtained via transthoracic echocardiography (TTE), and several measurements with more than one method are often needed to make an accurate diagnosis. ⁸ An MVA of >4.0 cm ² is normal, whereas an MVA of >2.0 to 4.0 cm ² indicates mild MS, >1.5 to 2.0 cm ² indicates moderate MS, and ≤1.5 cm ² indicates severe MS. In instances where the presence of calcification makes calculating MVA challenging, the projected transmitral gradient (TMG) can be used. ⁹ A projected TMG of ≥4 to 6 mm Hg indicates moderate MS and ≥6 mm Hg indicates severe MS. Table 3 summarizes evaluation of this entity.

Table 3. Evaluation of mitral annular calcification-related mitral stenosis.

Mitral valve calcification
	Extent of calcium (centripetal and circumferential) by 2D and 3D evaluation
	Depth of calcium in the posterior AV groove (if surgery is contemplated)
Transmitral pressure gradient
	Continuous wave Doppler
Mitral valve area
	Continuity equation (in the absence of MR and AR)
	2D and 3D planimetry
	Pressure half-time (not validated)

Abbreviations: 2D, two-dimensional; AML, anterior mitral leaflet; AR, aortic regurgitation; AV, atrioventricular; CT, computed tomography; IVRT, isovolumic relaxation time; LA, left atrium; LVOT, left ventricular outflow tract; MR, mitral regurgitation; MS, mitral stenosis.

Note: CT evaluation for AML length and neo-LVOT area (if transcatheter mitral valve replacement is contemplated).

The MVA can be calculated using two-dimensional (2D) planimetry, three-dimensional (3D) planimetry, pressure half-time, or the continuity equation. ^{10 11} The 2D or 3D planimetry methods are challenging due to difficulty in identifying the limiting orifice in the context of MAC and its acoustic shadowing. The pressure half-time method, which is well established in rheumatic MS, is unreliable because LV diastolic dysfunction is common among elderly patients with calcific MS. The continuity equation method is only accurate in the absence of significant aortic and MR.

Diagnosis of Mitral Annular Calcification-Related Mitral Stenosis—Mitral Valve Area

Two-Dimensional and Three-Dimensional Planimetry

Direct planimetry by 2D echocardiography, the gold standard for rheumatic MS, is not a reliable tool for MAC-related MS due to lack of commissural fusion causing the limiting mitral orifice to become nonplanar and to be near the calcified annular plane rather than at the leaflet tips. ¹² However, an attempt by 2D planimetry can be made by identifying the innermost border of the mitral orifice during maximal mitral opening in early diastole in the parasternal short-axis view under the lowest gain settings.

The primary limitations to this approach are high frequency of poor image quality, such as in the presence of calcification, leading to inadequate visualization of the mitral orifice, and inappropriately high- and low-gain settings yielding under- and overestimation of the true mitral orifice area, respectively.

Direct planimetry by 3D echocardiography, on the contrary, can overcome some of these limitations by displaying a unique “en face” view of the complete MV and its neighboring structures and is a promising technique for evaluation of MAC-related MS but presents substantial difficulties for use in daily clinical care. ¹³

Pressure Half-Time

The most frequently used measurement for the determination of the MVA is the pressure half-time method proposed by Hatle. ¹⁴

MVA = 220/pressure half-time in milliseconds

The pressure half-time is defined as the time required for the peak velocity to fall to one-half the square root of its peak value.

This approach can lead to inaccurate results if the LA–LV pressure gradient abruptly changes due to reasons other than inflow obstruction. ¹⁵ For instance, in aortic regurgitation, the pressure half-time method is likely to overestimate the true MVA. Similarly, under conditions of noncompliant LV, such as ischemic heart disease, the method is likely to underestimate the true MVA. As alluded to earlier, pressure half-time is unreliable in MAC-related MS.

Continuity Equation

According to the continuity equation, which is analogous to the law of conservation of mass in hemodynamics, during any given cardiac cycle, flow volume through the mitral annulus must be equal to the stroke volume (SV). Consequently, MVA can be defined as follows. ¹⁶

MVA = SV/TVI

TVI represents the time–velocity integral of mitral stenotic jet over one cardiac cycle.

Since SV is equivalent to the product of the aortic or pulmonic annulus cross-sectional area and TVI of aortic or pulmonic flow velocity, the equation can be rearranged to the following:

MVA = [aortic (or pulmonic) annular cross sectional area × TVIa (or TVIp)]/TVIm

TVIa and TVIp represent TVIs of the flow at the aortic and pulmonic annuli, respectively.

A major limitation to this methodology is that it underestimates the MVA in patients with associated MR.

Diagnosis of Mitral Annular Calcification-Related Mitral Stenosis—Projected Transmitral Pressure Gradient

The TMPG can be calculated using continuous wave Doppler. ⁹ However, since gradients are influenced by heart rate and SV, the equation for TMPG is modified to the following:

Projected TMPG (for men) = TMG – 0.07 * (heart rate [HR] – 70) – 0.03 * (SV – 97)

Projected TMPG (for women) = TMG – 0.08 * (heart rate [HR] – 72) – 0.04 * (SV – 84)

Management of Mitral Annular Calcification-Related Mitral Stenosis

Calcific MS presents several challenges. First, given the lack of commissural fusion, there is no role for percutaneous mitral balloon commissurotomy or surgical commissurotomy. Second, the presence of MAC can be quite challenging for the surgeon because of technical difficulty in securely attaching the prosthetic valve. Third, placement of the prosthetic valve may result in narrowing of the orifice. Fourth, if calcium is deep in posterior annulus, there is risk of atrioventricular disarticulation during surgery or damaging the circumflex coronary artery. Lastly, patients with calcification are often elderly and debilitated, have multiple comorbidities, and are at high surgical risk. For these reasons, intervention should be delayed until symptoms are severely limiting and cannot be managed with diuresis and heart rate control.

Medical Therapy

The cornerstone of MAC-related MS treatment remains medical management with diuretic therapy and, if there is significant inflow obstruction, heart rate control with a β-blocker, with the goal of optimizing diastolic filling time.

Valvular Interventions

Valvular interventions to directly address the MS, including surgical approach, the current gold standard treatment for severe MS, and transcatheter approach, are technically challenging and associated with a high degree of morbidity and mortality in this population. ^{17 18 19} Even after a successful procedure with significant reduction in transvalvular gradient, the mean LA pressure may remain elevated in the setting of poor LA and LV compliance, as is common in an elderly heart failure (HF) with preserved ejection fraction (EF) population. Therefore, only a subset of patients will benefit from valvular intervention, and this assessment is based on integration of patient-specific anatomical considerations, comorbidity burden, and patient goals of care and should be discussed on a case-by-case basis by the multidisciplinary heart valve team.

Valvular Interventions—Surgery

The two primary surgical approaches to severe symptomatic MAC-related MS are repair and replacement. Both techniques carry significant morbidity, such as atrioventricular disruption, long cardiopulmonary bypass and cross-clamp time, stroke, LA wall dissection, and injury to the circumflex artery, due to the underlying demographics.

Valvular Interventions—Transcatheter

Transcatheter MV implantation has emerged as a therapeutic option for patients with severe MAC-related MS who are deemed either high risk or unsuitable for conventional MV surgery.

The primary challenge with transcatheter MV implantation is adequate anchoring and seating of the valve prosthesis. This can be overcome by direct transatrial implantation of the prosthesis.

During and following intervention, one complication to be aware of is embolism. Another complication to be aware of is LV outflow tract obstruction, which occurs due to displacement of the anterior MV leaflet toward the interventricular septum by the transcatheter valve, and this contributes significantly to both 30-day and 1-year mortality.

The transcatheter mitral valve replacement (TMVR) in MAC Global Registry, initiated in October 2013, contains data related to TMVR using balloon-expandable valves in patients with MAC. Guerrero et al assessed 1-year outcomes in 106 patients with symptomatic severe MS with severe MAC ineligible for standard MV due to comorbidities or technical reasons related to calcium burden. ¹⁹ The 30-day mortality was 25% (29/116), whereas the 1-year mortality was 53.7% (57/106). Multivariate analysis revealed that the most important predictor of 1-year mortality was left ventricular outflow tract (LVOT) obstruction (hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.10–4.69, p  = 0.026), highlighting the magnitude of trying to avoid this important complication to improve outcomes.

Prognostic Factors in Mitral Annular Calcification-Related Mitral Stenosis

Pasca et al retrospectively looked at 1,004 patients with degenerative MS, defined as mean TMPG ≥ 2 mm Hg, between June 1995 and June 2011 to determine survival rates and survival determinants, and they discovered that the 1-, 5-, and 10-year survival rates were 78, 47, and 25%, respectively. ²⁰ Furthermore, the investigators reported that higher baseline MS grades were associated with lower 1- and 5-year survival. Multivariate Cox regression model revealed that older age (Hazard Ratio: 1.11, 95% CI: 1.06–1.17, p  < 0.0001), renal insufficiency (Hazard Ratio: 1.39, 95% CI: 1.25–1.51, p  < 0.0001), atrial fibrillation (AFib; Hazard Ratio: 1.42, 95% CI: 1.10–1.71, p  = 0.0011), tricuspid regurgitation (Hazard Ratio: 1.15, 95% CI: 1.05–1.24, p  = 0.0072), and aortic stenosis (Hazard Ratio: 1.10, 95% CI: 1.02–1.18, p  = 0.033) were independent predictors of mortality. Similarly, Kuyama et al retrospectively reviewed 113 patients with echocardiographic evidence of degenerative MS, defined as mean TMPG ≥ 2 mm Hg, between January 2014 and December 2017 to identify disease progression determinants, and they found that dyslipidemia (odds ratio [OR]: 2.47, 95% CI: 1.15–5.47, p  = 0.02) and coronary artery disease (CAD; OR: 2.58, 95% CI: 1.16–5.92, p  = 0.02) were predictors of worsening MS. ²¹

Future Directions

A key path of future research will be to better define which patients are likely to benefit from valvular interventions.

The ongoing MITRAL II pivotal trial plans to recruit 110 patients at high operative risk with severely symptomatic MAC-related MV dysfunction (defined as severe MAC with MVA ≤ 1.5 cm ² and/or more than moderate MR) for transseptal valve-in-MAC implantation.

Mitral Valve Regurgitation

Introduction

MR is a common valvular abnormality in elderly. A population-based study by Nkomo et al looked at the valvular heart disease burden and impact on survival in general population has reported MR had highest prevalence and least prevalent was MS. ² This study also reported with increasing age MR prevalence also increased. Framingham Heart study showed the prevalence of MR to be 11.1% in men age between 70 and 83 years. With the population of elderly expected to triple by 2050 in the United States, it is important to recognize and manage these valvular abnormalities appropriately. ²²

Types of Mitral Regurgitation

MR is divided into primary versus secondary based on the etiology. Secondary also called as functional MR is further divided into ischemic versus nonischemic depending on the cause of MR ( Table 4 ). ²³

Table 4. Primary and secondary mitral regurgitation.

Primary MR (primary abnormalities in mitral valve apparatus)	(1) Myxomatous degeneration (2) Barlow's disease (3) Fibroelastic deficiency (4) Leaflet perforation and cleft leaflets (5) Rheumatic disease (6) Drugs (7) Radiation (8) Connective tissue diseases (9) Mitral annular calcification
Secondary MR (LV dysfunction)	(1) Global LV dilation and dysfunction (2) Focal wall motion abnormalities (inferobasal akinesis or dyskinesis) (3) LV dys-synchrony due to bundle branch block or right ventricular pacing (4) Atrial functional MR—mitral annular dilation secondary to atrial fibrillation or restrictive cardiomyopathy (5) Mitral annular disjunction

Abbreviations: LV, left ventricle; MR, mitral regurgitation.

• (1) Primary MR is caused by dysfunction of intrinsic valvular or sub-valvular apparatus such as MV prolapse, calcific degeneration, ruptured chordae tendineae, infective endocarditis, rheumatic heart disease, congenital malformations like valve cleft, MAC, use of certain drugs like ergotamine, bromocriptine etc.

• (2) Secondary ischemic functional MR is the most common in elderly population secondary to wall motion abnormalities, which result in mitral leaflet tethering. The MV leaflets and chords are normal. Papillary muscle infarction causing papillary muscle rupture is rare but will result in torrential MR and pulmonary edema/cardiogenic shock.

• (3) Secondary nonischemic MR is usually due to mitral annular dilation and bileaflet tethering or tenting because of LV dilation due to any cause other than ischemia. Isolated LA dilation as it occurs in AFib or restrictive physiology may also cause isolated mitral annular dilation and MR (our paper, isolated LA enlargement causing MR). ²⁴

Diagnosis of Mitral Regurgitation—History and Physical

Diagnosis of MR is suspected with specific history of fatigue and exercise intolerance. Physical examination can hint the cause and severity of MR. A holosystolic murmur is typically audible. Severe MR can cause diastolic rapid filling, yielding a hyperdynamic apical impulse. ⁷ One must be concerned for a flail leaflet if a new holosystolic murmur or late systolic murmur is detected in a patient without a previously reported click. The leaflet involved can be identified by the direction of radiation of the murmur. Anterior leaflet prolapse causes a murmur directed posteriorly, whereas posterior leaflet prolapse causes the murmur to radiate anteriorly. ²³

Diagnosis of Mitral Regurgitation—using Different Imaging Modalities

Color flow Doppler echocardiography has increased the sensitivity of detecting MR even in asymptomatic patients. MR should be suspected in a patient with apical holosystolic murmur or mid to late systolic murmur. A majority of the patients are asymptomatic until late in the disease. ²⁵ The diagnosis is usually confirmed by TTE. Since MR causes a chronic volume overload state, the LA and LV are typically dilated. Specifically, the LV undergoes eccentric hypertrophy. Transesophageal echocardiography (TEE) is done to better quantify severity of MR and also guide transcatheter therapies. Recently with the development of TMVR, other modalities like multidetector computer tomography has become standard before any intervention because of its ability to assess size of the valve, access site, outflow tract obstruction. ²⁶ The goal is to determine the cause, severity, and hemodynamic changes to help determine further management ( Fig. 2 ).

Fig. 2.

Suggested workup for MR. H&P, history & physical; MR, mitral regurgitation; L, left.

Diagnosis of Mitral Regurgitation—Severity

The severity of MR is determined based on integrative approach with physical examination giving a hint confirmed by further quantitative and qualitative measurements. Loud holosystolic murmur associated with diastolic rumble along with displaced apical impulse on physical examination can give a clue of severe MR. In patients with HF, the murmur of severe MR might be inaudible. ²⁷ Echocardiographic findings of normal LA and LV size excludes severe chronic MR. ²⁸ Flail leaflet associated with eccentric jet is a specific finding for severe MR. Color flow doppler is used to screen for severity of MR by looking at the size and direction of the jet. Small regurgitant jet with high velocity can be misread as severe because Doppler identifies velocity. ²⁹ Flail leaflets are diagnosed by seeing the free edge of the leaflet prolapsing into the LA and an eccentric holosystolic regurgitation. Presence of pulmonary hypertension or high transmitral E-wave velocity indicates severe MR. Pulmonary vein signal showing systolic flow reversal, peak-E wave of greater than 1.2 m/s are also signs concerning for severe MR. ²⁸

Large jet area on color Doppler is an indication for severe MR. Due to Coanda effect visual assessment of the size of the eccentric color flow jet can underestimate the actual severity of MR. ³⁰ Regurgitate volume (RVol), effective regurgitate orifice area (EROA) calculated using PISA (proximal isovelocity surface area) or the continuity method and regurgitant fraction (RF) are quantitative measurements needed to be correlated clinically and interact in a complicated manner. A large EROA can have small or large RVol based on the driving velocity across the valve similarly a given EROA or RVol can have different RF based on the LV end-diastolic volume and left ventricular ejection fraction (LVEF). All guidelines use these parameters together to define mild, moderate, or severe MR. ³¹

With multimodality imaging like 3D echo, magnetic resonance imaging (MRI), or computed tomography (CT) scanning available to assess LV volumes, no study has been validated using these modalities. Currently, the timing of intervention is based on the LV dimensions from parasternal long-axis view taken at the level of papillary muscles. The presence of regional wall motion abnormalities decreases the reliability of the study. ³²

Given the complexity of MV anatomy, there is sometimes difference between the severity of physical examination findings and measurements on TTE in these situations further testing with TEE, MRI, or cardiac catheterization is used to define the mechanism and severity ( Table 5 ). Augmentation of blood pressure with phenylephrine while performing TEE can be helpful in eliciting underlying severe MR.

Table 5. Helpful tests and their value in patients with mitral valve disease.

TEE	Poor TTE images Prior to and during planned MV surgery
Exercise testing	To ascertain the functional capacity accurately in patients with poor history and patients with discordance between symptoms and echocardiographic severity of MR
CMR	When echocardiography is inadequate to quantify
Coronary angiography	Should be done prior to valve surgery in patients who have CAD or at risk for CAD as the obstructive lesions can be bypassed during MV surgery
BNP levels	May have prognostic value

Abbreviations: BNP, B-type natriuretic peptide; CAD, coronary artery disease; CMR, cardiovascular magnetic resonance; MR, mitral regurgitation; MV, mitral valve; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography.

Diagnosis of Mitral Regurgitation—Determining Repairability

It is important to consider the feasibility of successful valve repair. Valve morphology and surgical expertise determine the success rate. Degenerative disease and chordal rupture of posterior leaflet have higher success rate. Presence of annular calcification, calcification and fibrosis of leaflets makes the repair extremely difficulty. Localized posterior leaflet, carpenter type 1 prolapse is easy to repair whereas complex anatomy like anterior leaflet prolapse, bileaflet prolapse and rheumatic heart disease should only be undertaken by experts in high-volume centers. ³³

Once the mechanism and severity of MR have been established next step would be detailed evaluation of anatomy using 3D TEE and multidetector CT to determine the safety and feasibility of different procedures. Transcatheter approaches have device specific requirements. These procedures also require intraprocedural TEE so preprocedural TEE is required to demonstrate image quality. If surgical valve replacement is considered, then concurrent tricuspid repair possibility should also be evaluated as well for feasibility of minimally invasive approach is a possibility. ²³

Management of Primary Mitral Regurgitation

The management of primary MR is based on the grade of the disease. Grade A involves mild MV abnormalities with no major valve hemodynamic changes. Grade B involves intermediate valve hemodynamics with mild LA enlargement. Grade C involves criteria for severe valvular hemodynamics without symptoms. It is further classified into C1 and C2 based on the LVEF and left ventricular end-systolic diameter (LVESD). Grade D involves symptomatic MR with severe valve hemodynamics ( Table 6 ). ³⁴

Table 6. Stages of mitral valve regurgitation.

Grade	Valve anatomy	Valve hemodynamic	Hemodynamic consequences	Symptoms
A (At risk for MR)	Mild MVP Mild leaflet thickening and leaflet restriction	No or small MR Central MR jet with area < 20% LA Small vena contract < 0.3 cm	None	None
B (Progressive MR)	Severe MVP Rheumatic valve changes with leaflet restriction and loss of central coaptation Prior IE	Central MR jet 20–40% LA or late systolic eccentric jet MR Small vena contract < 0.7 cm Regurgitant volume < 60 mL Regurgitant fraction < 50% EROA < 0.40 cm 2 Angiographic grade 1–2+	Mild LA enlargement	None
C (Asymptomatic severe MR)	Severe MVP with loss of coaptation or flail leaflet Rheumatic valve changes with leaflet restriction and loss of central coaptation Prior IE Thickening of leaflets with radiation heart disease	Central MR jet > 40% LA or holosystolic eccentric jet MR Vena contract ≥ 0.7 cm Regurgitant volume ≥ 60 mL Regurgitant fraction ≥ 50% EROA [FO]0.40 cm 2 Angiographic grade 3–4+	Moderate or severe LA enlargement Pulmonary HTN at rest or exercise C1:LVEF > 60% and LVESD < 40mm C2:LVEF ≥ 60% and LVESD [FO]40 mm	None
D (Symptomatic severe MR)	Severe MVP with loss of coaptation or flail leaflet Rheumatic valve changes with leaflet restriction and loss of central coaptation Prior IE Thickening of leaflets with radiation heart disease	Central MR jet > 40% LA or holosystolic eccentric jet MR Vena contract ≥ 0.7 cm Regurgitant volume ≥ 60 mL Regurgitant fraction [FO]50% EROA [FO]0.40 cm 2 Angiographic grade 3–4+	Moderate or severe LA enlargement Pulmonary HTN at rest or exercise	Heart failure

Abbreviations: EROA, effective regurgitate orifice area; HTN, hypertension; IE, infective endocarditis; LA, left atrium; LVESD, left ventricular end-systolic diameter; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; MVP, mitral valve prolapse.

Management of Primary Mitral Regurgitation—Monitoring

Following initial evaluation and staging, serial monitoring (and restaging) is warranted. Serial TTE should be done to determine the change in MR grade, the frequency of follow-up depends on MR severity ( Table 7 ).

Table 7. Recommended follow-up for asymptomatic mitral regurgitation without left ventricular dilation or dysfunction.

Mild MR	Annual history and physical exam TTE every 3–5 y
Moderate MR	Annual history and physical exam TTE every 1–2 y
Severe MR	Annual History and physical exam TTE every 6–12 mo

Abbreviations: MR, mitral regurgitation; TTE, transthoracic echocardiography.

Management of Primary Mitral Regurgitation—Medical Therapy

The role of medical therapy is limited in primary MR. Afterload reduction with antihypertensives in hypertensive patients and guideline-directed medical therapy (GDMT) in patients with low EF (<60%) have shown some benefits. ^{11 35} In asymptomatic patients with normal LV function, vasodilator therapy is not indicated. The role of β-blockers in Grades A and B MR is an area of ongoing research. ³⁶

Management of Primary Mitral Regurgitation—Interventions

In patients with chronic primary MR, the need for intervention is based upon MR severity, presence of symptoms, LVESD and LVEF, and the feasibility of repair, among other factors ( Fig. 3 ).

Fig. 3.

Decision-making in severe MR patients having an indication for surgery. GDMT, guideline-directed medical therapy; LVEF, left ventricular ejection fraction; LV, left ventricle; MR, mitral regurgitation; MV, mitral valve; NYHA, New York Heart Association.

The ideal time for MV intervention is when the patient's LV has not yet reached the parameters that indicate systolic dysfunction (LVEF ≤ 60% or LVESD ≥ 40 mm). ⁵ Surgical treatment may be considered in patients with new-onset AFib, pulmonary hypertension, or progressive worsening of LV parameters. In symptomatic severe MR (Stage D) regardless of EF and asymptomatic severe primary MR with LV systolic dysfunction (LVEF ≤ 60%, LVESD ≥ 40 mm) (Stage C2), MV intervention is recommended (Class I recommendation). MV repair is preferred over replacement for degenerative disease if a successful and durable repair is possible. ³⁷ For asymptomatic patients with chronic severe primary MR and normal LV function (stage C1) with a high likelihood of a successful and durable MV repair and expected mortality rate of <1% or those with a progressive increase in LV size or decrease in LVEF on serial imaging studies, MV repair is suggested. However, symptomatic patients at a prohibitive surgical risk may be considered for transcatheter MV intervention.

Management of Secondary Mitral Regurgitation

Secondary MR staging is based on symptoms, valve anatomy, and hemodynamics.

Management of Secondary Mitral Regurgitation—Monitoring

Patients require serial monitoring following an initial evaluation and staging to assess changes in clinical status and MR severity ( Table 6 ).

Management of Secondary Mitral Regurgitation—Medical Therapy

First-line therapy for secondary MR is the management of heart failure with reduced ejection fraction (HFrEF) and the management of concurrent conditions, particularly underlying CAD. Patients with chronic secondary MR and LV dysfunction should receive standard evidence-based therapy for HFrEF, including angiotensin-converting enzyme inhibitor/ARB/ARNI, β-blocker and mineralocorticoid receptor antagonist, and diuretic therapy as needed. ³⁸ Patients with chronic functional MR should receive cardiac resynchronization therapy (CRT) according to standard guidelines for CRT (left bundle branch block, QRS duration > 150 ms). For underlying CAD treatment, standard recommendations for coronary revascularization apply. ³⁹ Revascularization may also reduce the severity of MR if a significant area of stunned, or hibernating myocardium is present. ^{40 41}

Management of Secondary Mitral Regurgitation—Intervention

Indications for intervention and type of intervention depend on the clinical presentation and presence of a concurrent indication for other cardiac surgery ( Fig. 4 ). For patients with severe chronic secondary MR with LVEF ≤ 50% and severe persistent symptoms (NYHA [New York Heart Association] II–IV HF), despite optimal GDMT, transcatheter edge-to-edge repair can be considered if they have favorable anatomy (Class IIa recommendation). Favorable anatomy is defined on TEE as LVEF between 20 and 50%, LVESD ≤ 70 mm, and pulmonary artery systolic pressure ≤ 70 mm Hg. In patients with chronic severe secondary MR from atrial annular dilation with preserved LV systolic function (LVEF ≥ 50%) and severe persistent symptoms (NYHA Class III or IV) despite therapy for HF and therapy for associated AF or other comorbidities (Stage D), MV surgery may be considered. For patients with chronic severe secondary MR who are undergoing coronary artery bypass grafting (CABG), MV surgery is reasonable (Class IIa). The choice of surgical procedure (surgical MV repair or replacement) varies with the cause of MR, but MV replacement with chordal sparing is preferred over MV repair. Survival is similar following MV replacement and surgical MV repair. ⁴² However, recurrent MR is much more frequent following surgical MV repair. There are limited data on the efficacy and safety of isolated MV surgery (without CABG) for secondary MR.

Fig. 4.

Management of moderate or severe symptomatic MR in patients with heart failure and LVEF < 50%. CABG, coronary artery bypass graft; CHFrEF, congestive heart failure with recovered ejection fraction; CRT, cardiac resynchronization therapy; GDMT, guideline-directed medical therapy; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; PCI, percutaneous coronary intervention; TEER, transcatheter edge-to-edge repair.

Valve-in-Valve Transcatheter Valve Replacement

Since the life expectancy in these patients is higher, due to wear and tear the prosthetic valves will eventually fail. When a patient presents with a degenerated bioprosthetic valve stenosis or regurgitation, TMVR is a viable option. ^{43 44} The gold standard is still a redosurgical valve replacement, but TMVR with commonly available Edwards SAPIEN valve (Edwards Life Sciences, Irvine, CA) is used when surgery comes with high risk. The most common approach for TMVR is transeptal approach with apical approach being less commonly used. TEE and fluoroscopy are used for guiding of TMVR. Prior to the planned procedure imaging with dedicated cardiac computed tomography (CCT) and TEE is recommended to ascertain the following measurements.

• Valve size determination: valve size (actual internal dimension of the failed bioprosthetic valve) can also be determined by using TEE and by CCT.

• Measure aortomitral angle: recommended favorable angle is >105 degrees.

• Measure neo-LVOT area: this is measured after implanting a virtual implantation of SAPIEN valve. The recommended area is >200 mm ² to prevent LVOT obstruction.

• In cases where the interventricular septum is too thick and predicted neo-LVOT area is <200 mm ² , then alcohol septal ablation can be undertaken prior to TMVR. A newer method, balloon-assisted anterior MV translocation can be utilized to prevent neo-LVOT obstruction.

Success rate with TMVR is in the range of 94 to 97%, 30-day survival of 91 to 95%with 86% 1-year survival. ⁴⁴

Other Potential Mitral Regurgitant Valve Lesions Potentially Amenable to Transcatheter Treatment

Transcatheter delivery of a clip to bring culprit segments of anterior and mitral leaflets together is another nonsurgical option. This is a catheter version of Alfieri stitch. The clip is deployed on to the mitral leaflets through a transvenous, transapical approach under general anesthesia and TEE guidance. Figs. 5 and 6 are two such examples that can be treated quite well with transcatheter MV clip. Fig. 7 shows the result of successful mitral clip procedure where MR is eliminated. Fig. 8 is an example of severe MR due to perforation of anterior mitral leaflet secondary to infective endocarditis, and this was treated successfully because of prohibitive surgical risk, with an Amplatzer plug after infection control ( Fig. 9 ).

Fig. 5.

TEE demonstrating bi-leaflet mitral valve prolapse causing severe MR. Although this is amenable to both mitral valve repair and mitral valve replacement, transcatheter edge to edge repair is preferred in elderly patients. LA, left atrium; LV, left ventricle; MR, mitral regurgitation; TEE, transesophageal echocardiogram.

Fig. 6.

TEE demonstrating functional MR due to bi-leaflet mitral valve leaflet tethering secondary to LV dilation. LA, left atrium; LV, left ventricle; MR, mitral regurgitation; TEE, transesophageal echocardiogram.

Fig. 7.

3D TEE demonstrating transcatheter deployment of a MitraClip to bring together A2 and P2 to eliminate MR in a patient with flail P2. 3D, 3 dimensional; A, anterior; AML, anterior mitral leaflet; P, posterior; PML, posterior mitral leaflet; TEE, transesophageal echocardiogram; MR, mitral regurgitation.

Fig. 8.

TEE demonstrating a perforated anterior mitral valve leaflet due to prior endocarditis. When MR is severe and symptomatic, surgical repair is the preferred choice. However, in high-risk patients with conducive location and anatomy, repair is an alternative option. Ao, aorta; LA, left atrium; LV, left ventricle; MR, mitral regurgitation; TEE, transesophageal echocardiogram.

Fig. 9.

Transcatheter plugging of perforation in the base of anterior mitral leaflet with an Amplatzer II plug resulting in complete resolution of MR. MR, mitral regurgitation.

Summary

In summary, MV disease in the elderly poses many special problems and considerations such as heavy MAC, multiple medical comorbidities, advanced age, potentially poor functional status and frailty, presence of CAD, and a stiffer ventricle, etc. All these have to be taken into consideration in the decision-making. In the presence of multiple cardiac issues, it is also important to determine the potential contribution from the dominant valvular issue and if correcting that will improve hemodynamics, functional status and prognosis. These issues are best discussed by a multidisciplinary cardiac team.