Mitral Valve Regurgitation: Pathophysiology, Epidemiology, Diagnostics, Treatment Modalities, and Long-Term Outcomes

Abstract

Mitral Valve Regurgitation (MVR) stands as a highly prevalent and clinically significant valvular heart disease, fundamentally characterized by the abnormal backflow of blood from the left ventricle into the left atrium during ventricular systole. This pathological phenomenon results from the incomplete coaptation of the mitral valve leaflets. MVR is broadly classified into two primary categories: primary (or degenerative) MVR, which arises from intrinsic structural abnormalities of the mitral valve apparatus, and secondary (or functional) MVR, which occurs as a consequence of left ventricular (LV) dysfunction and remodeling, without direct structural damage to the valve leaflets themselves. Each classification presents distinct etiologies, pathophysiological mechanisms, and clinical trajectories, necessitating a nuanced approach to diagnosis and management. The timely and accurate identification of MVR, coupled with an appropriate, individualized therapeutic strategy, is paramount to mitigate its progressive nature and prevent severe adverse outcomes, including the development of heart failure, life-threatening arrhythmias, and premature mortality. This comprehensive report aims to provide an in-depth exploration of MVR, encompassing its intricate anatomy and physiology, detailed pathophysiological mechanisms for both primary and secondary forms, global and regional epidemiological patterns, advanced diagnostic techniques, a full spectrum of current and emerging treatment modalities, meticulous patient selection criteria for intervention, and an analysis of long-term outcomes and their impact on patient quality of life. The objective is to synthesize current knowledge, highlighting the evolving landscape of MVR management.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

1. Introduction

The mitral valve, a critical component of the heart’s circulatory system, acts as a sophisticated one-way gate positioned between the left atrium and the left ventricle. Its primary role is to ensure unidirectional blood flow, preventing the backward leakage of oxygenated blood into the left atrium during ventricular contraction (systole) and allowing unimpeded forward flow from the atrium to the ventricle during ventricular relaxation (diastole). Mitral Valve Regurgitation (MVR) signifies a failure of this crucial valvar mechanism, where the mitral valve does not close completely, leading to a pathological reverse flow of blood into the left atrium during systole. This persistent backflow, known as the regurgitant jet, imposes a chronic volume overload on both the left atrium and the left ventricle. The immediate hemodynamic consequence is an increase in left atrial pressure and volume, which can be transmitted backward to the pulmonary circulation, leading to pulmonary hypertension and congestion. Simultaneously, the left ventricle must pump a larger stroke volume to maintain adequate forward systemic output, leading to compensatory dilation and hypertrophy. Over time, if left unaddressed, this sustained volume overload can lead to progressive left ventricular remodeling, characterized by eccentric hypertrophy, chamber dilation, contractile dysfunction, and ultimately, the symptomatic manifestation of congestive heart failure. Beyond its direct impact on cardiac mechanics, MVR significantly increases the risk of atrial fibrillation, a common and debilitating arrhythmia, and can precipitate adverse outcomes such as stroke and diminished functional capacity.

The dichotomy of MVR into primary and secondary forms is fundamental to its understanding and management. Primary MVR, often referred to as degenerative MVR, involves an intrinsic structural defect of the valve leaflets, chordae tendineae, annulus, or papillary muscles. These defects directly impair the valve’s ability to coapt properly. In contrast, secondary MVR, also termed functional MVR, arises not from a problem with the valve itself, but as a consequence of underlying left ventricular disease that alters the geometry and function of the LV and its supporting structures (papillary muscles and annulus), thereby preventing normal leaflet closure. This distinction carries profound implications for diagnostic evaluation, prognosis, and, critically, for the choice and timing of therapeutic interventions. Given the significant burden of MVR on global health and the rapid advancements in its diagnosis and treatment, a thorough understanding of its multifaceted nature is indispensable for clinicians and researchers alike.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

2. Anatomy and Function of the Mitral Valve Apparatus

To fully appreciate the pathophysiology of MVR, a detailed understanding of the normal anatomy and intricate coordinated function of the mitral valve apparatus is essential. The mitral valve is not merely a pair of leaflets but a highly complex and dynamic functional unit comprising six distinct, yet interdependent, components, often referred to as the ‘mitral valve complex’ or ‘mitral valve apparatus’. Its structural integrity and synchronized movement are paramount for effective ventricular contraction and the prevention of regurgitation.

2.1 Mitral Annulus

The mitral annulus serves as the fibrous ring that provides structural support for the mitral leaflets and demarcates the boundary between the left atrium and left ventricle. It is a D-shaped, saddle-shaped structure, not a perfect circle, which undergoes dynamic changes throughout the cardiac cycle. During ventricular systole, the annulus contracts, reducing its area and circumference, which facilitates leaflet coaptation and contributes to valve competence. In diastole, it expands to allow maximal blood flow into the ventricle. Its proximity to the fibrous trigones – the right fibrous trigone connecting the mitral, aortic, and tricuspid valves, and the left fibrous trigone connecting the mitral and aortic valves – anchors it within the cardiac skeleton. Pathological dilation of the LV can stretch the annulus, particularly its posterior and lateral segments, preventing proper leaflet coaptation and leading to secondary MVR. (medtechnews.uk)

2.2 Mitral Leaflets

The mitral valve consists of two primary leaflets: the anterior (aortic) leaflet and the posterior (mural) leaflet. These leaflets are thin, pliable, and composed of three distinct layers: the atrialis (facing the atrium), spongiosa (middle layer, rich in proteoglycans), and fibrosa (ventricular side, collagen-rich).

• Anterior Leaflet: This leaflet is typically larger and semilunar in shape, occupying approximately one-third of the annular circumference but accounting for two-thirds of the total leaflet area. It is directly continuous with the non-coronary and left coronary cusps of the aortic valve, forming part of the ‘aortic-mitral curtain’. Its mobility is crucial for both inflow during diastole and outflow during systole.
• Posterior Leaflet: The posterior leaflet is crescent-shaped, occupying approximately two-thirds of the annular circumference but only one-third of the total leaflet area. It is typically divided into three scallops: P1 (anterior or anterolateral), P2 (middle), and P3 (posterior or posteromedial). This segmented structure allows for greater flexibility and adaptation to ventricular geometry during systole. Abnormalities in either leaflet, such as prolapse, thickening, restriction, or perforation, directly compromise valve closure and result in regurgitation.

2.3 Chordae Tendineae

Connecting the free edges and ventricular surfaces of the mitral leaflets to the papillary muscles, the chordae tendineae are thin, fibrous strings primarily composed of collagen and elastin. They play a critical role in preventing the leaflets from prolapsing or everting into the left atrium during ventricular systole when subjected to high ventricular pressures. The chordae are categorized by their insertion points:

• Primary Chordae: Insert into the free edge of the leaflets, preventing prolapse.
• Secondary Chordae: Insert into the ventricular surface of the leaflets, providing additional structural support and maintaining ventricular geometry.
• Tertiary Chordae: Insert into the base of the posterior leaflet and connect to the ventricular wall, contributing to annular-leaflet stability.

Rupture, elongation, thickening, or fusion of these chordae can lead to severe MVR by allowing leaflet prolapse or restricting leaflet motion. (scivast.com)

2.4 Papillary Muscles

There are typically two papillary muscles within the left ventricle: the anterolateral and posteromedial. They originate from the ventricular wall and project into the ventricular cavity, terminating in tendinous heads from which the chordae tendineae arise.

• Anterolateral Papillary Muscle: Usually larger and supplied by both the left anterior descending and circumflex arteries, making it less prone to isolated ischemic injury.
• Posteromedial Papillary Muscle: Typically smaller and supplied primarily by the posterior descending artery (a branch of the right coronary artery in 80-85% of individuals, or the circumflex artery in 15-20%), making it more vulnerable to ischemia and rupture during myocardial infarction.

During systole, the papillary muscles contract simultaneously with the ventricular free wall, maintaining appropriate tension on the chordae tendineae to prevent leaflet prolapse. Dysfunction, displacement, or rupture of these muscles, often due to ischemia or infarction, profoundly impacts leaflet coaptation and is a major cause of secondary MVR. (kardio.hr)

2.5 Left Atrium and Left Ventricle

The left atrium (LA) and left ventricle (LV) are integral components of the functional mitral apparatus. The LA serves as a reservoir during ventricular systole and a conduit during early diastole. Chronic volume overload from MVR causes LA enlargement, which can lead to atrial fibrillation and further exacerbate annular dilation. The LV provides the contractile force for blood ejection. Changes in LV size, shape, and contractility, particularly ventricular dilation and remodeling, directly affect the geometry of the entire mitral apparatus, leading to leaflet tethering and secondary MVR. The complex interplay of these six components ensures the synchronized closure and opening of the mitral valve, maintaining cardiovascular efficiency. Any disruption to one or more of these components can lead to MVR.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

3. Pathophysiology of Mitral Regurgitation

MVR is fundamentally a disorder of mitral valve closure, leading to retrograde blood flow. The underlying mechanisms differ significantly between primary and secondary forms, impacting clinical presentation and therapeutic strategies.

3.1 Primary Mitral Regurgitation (Degenerative/Organic)

Primary MVR results from intrinsic structural abnormalities of the mitral valve apparatus itself. These conditions directly impair leaflet coaptation by causing excessive leaflet motion (prolapse or flail) or restricted motion due to leaflet thickening and rigidity.

3.1.1 Mitral Valve Prolapse (MVP)

MVP is the most common cause of primary MVR in developed countries and is characterized by the displacement of one or both mitral leaflets into the left atrium during ventricular systole. This displacement leads to incomplete coaptation and subsequent regurgitation. MVP is a spectrum of disorders, from benign forms to severe myxomatous degeneration resulting in significant MVR.

• Etiology and Pathology: MVP is predominantly caused by myxomatous degeneration, a disorder of the connective tissue within the valve leaflets and chordae. This involves an accumulation of proteoglycans (acid mucopolysaccharides) and disorganization of collagen and elastin fibers, leading to leaflet thickening, redundancy, and elongation.
  • Barlow’s Disease (Diffuse Myxomatous Degeneration): This is a more severe, often familial form involving marked thickening and redundancy of both leaflets and chordal elongation. It can lead to severe regurgitation and is typically seen in younger individuals. Histologically, there is extensive disruption of the fibrosa layer. (en.wikipedia.org)
  • Fibroelastic Deficiency: A more localized and less severe form, often seen in older individuals, characterized by thinning and elongation of chordae, which may rupture, particularly affecting a single scallop of the posterior leaflet (most commonly P2). The leaflets themselves may appear relatively normal in thickness but become redundant due to chordal rupture, leading to a flail leaflet. This type is frequently amenable to surgical repair.
• Mechanisms of Regurgitation: The primary mechanisms are excessive leaflet motion (prolapse or flail) due to chordal elongation or rupture, or severe leaflet redundancy that prevents complete closure. The degree of leaflet displacement and the resultant coaptation defect determine the severity of MVR. Flail leaflets (where a leaflet segment loses chordal support and freely swings into the left atrium) are associated with sudden onset of severe MVR. (ncbi.nlm.nih.gov)
• Clinical Implications: MVP can range from an asymptomatic condition to severe MVR requiring intervention. It is sometimes associated with connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, which predispose individuals to generalized connective tissue abnormalities, including those affecting the heart valves.

3.1.2 Rheumatic Heart Disease

Rheumatic heart disease (RHD) is a serious sequela of acute rheumatic fever (ARF), an autoimmune inflammatory process triggered by an untreated Group A streptococcal infection. While its incidence has declined significantly in developed countries due to improved hygiene and antibiotic availability, RHD remains a major public health concern in developing regions, particularly among children and young adults.

• Pathology: The inflammatory response in RHD targets cardiac tissues, leading to chronic scarring and deformation of the heart valves. In the mitral valve, the hallmark pathological changes include:
  • Leaflet Thickening and Fibrosis: The leaflets become rigid, thickened, and calcified, losing their normal pliability.
  • Commissural Fusion: The junctions between the leaflets (commissures) fuse, restricting leaflet opening (causing mitral stenosis) and often leading to incomplete closure during systole (causing MVR).
  • Chordal Shortening and Fusion: The chordae tendineae become thickened, shortened, and fused, tethering the leaflets and preventing their full excursion and proper coaptation.
• Mechanisms of Regurgitation: The restricted motion and structural distortion of the leaflets and chordae prevent effective closure. Often, rheumatic MVR coexists with mitral stenosis, creating a complex mixed valve lesion. The thickened, retracted leaflets create a fixed regurgitant orifice. (pubmed.ncbi.nlm.nih.gov)
• Clinical Implications: RHD often presents as a slowly progressive disease, with symptoms developing decades after the initial ARF episode. It can lead to severe heart failure, pulmonary hypertension, and atrial fibrillation.

3.1.3 Infective Endocarditis

Infective endocarditis (IE) is a microbial infection of the endocardial surface of the heart, most commonly affecting the heart valves. While any valve can be affected, the mitral valve is frequently involved, particularly in individuals with pre-existing valve disease or prosthetic valves.

• Pathology: IE leads to the formation of vegetations – friable masses of platelets, fibrin, microorganisms, and inflammatory cells – on the valve leaflets. These vegetations can directly interfere with valve closure. More destructively, enzymatic degradation by the infecting organisms and the host’s inflammatory response can cause:
  • Leaflet Perforation: Direct destruction of leaflet tissue, creating a hole through which blood regurgitates.
  • Chordal Rupture: Weakening and rupture of chordae tendineae, leading to a flail leaflet segment and acute severe MVR.
  • Annular Abscess Formation: Infection extending into the mitral annulus, potentially leading to dehiscence of prosthetic valves or severe structural damage. (pubmed.ncbi.nlm.nih.gov)
• Mechanisms of Regurgitation: Direct valve destruction (perforation), loss of chordal support (flail leaflet), or interference with coaptation by large vegetations are the primary mechanisms. IE often results in acute, severe MVR, which can lead to rapid hemodynamic decompensation and cardiogenic shock, requiring urgent surgical intervention.

3.1.4 Other Rare Causes of Primary MVR

Less common causes include:
* Congenital Mitral Valve Abnormalities: Cleft mitral valve (often associated with atrioventricular septal defects), parachute mitral valve (single papillary muscle with all chordae attached), or hypoplastic leaflets.
* Trauma: Blunt chest trauma can, in rare cases, lead to chordal rupture or papillary muscle avulsion.
* Drug-Induced Valvulopathy: Certain medications, such as ergot alkaloids and fenfluramine derivatives (now withdrawn), have been associated with fibrotic changes in heart valves, including the mitral valve, causing regurgitation.
* Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome: Can cause non-bacterial thrombotic endocarditis (Libman-Sacks endocarditis) with vegetations that lead to leaflet damage and MVR.

3.2 Secondary Mitral Regurgitation (Functional/Ischemic)

Secondary MVR occurs when there are no intrinsic structural abnormalities of the mitral valve leaflets themselves. Instead, it arises from pathological changes in the left ventricle that alter the geometry of the mitral valve apparatus, preventing proper leaflet coaptation. It is fundamentally a disease of the left ventricle affecting the mitral valve.

3.2.1 Ischemic Heart Disease

Ischemic heart disease, particularly myocardial infarction (MI), is a leading cause of secondary MVR. The damage to myocardial tissue and subsequent remodeling significantly alters LV geometry.

• Acute Ischemic MVR: Can occur acutely after an MI due to:
  • Papillary Muscle Dysfunction or Rupture: This is a catastrophic complication, particularly of inferoposterior MIs affecting the posteromedial papillary muscle. Rupture leads to sudden, massive MVR and cardiogenic shock. Dysfunction without rupture can also cause acute tethering. (jcdronline.org)
  • Regional Wall Motion Abnormalities: Stunned or hibernating myocardium in the vicinity of papillary muscles can lead to their displacement and tethering of leaflets.
• Chronic Ischemic MVR: Develops over time in patients with chronic ischemic heart disease and recurrent MIs, leading to significant LV remodeling.
  • Ventricular Dilation and Spherical Remodeling: As the LV dilates and changes from an elliptical to a more spherical shape, the papillary muscles are displaced laterally and apically. This increases the distance between the papillary muscles and the mitral annulus, creating tension on the chordae tendineae.
  • Leaflet Tethering: The tension on the chordae pulls the leaflets towards the apex of the ventricle, restricting their normal systolic closure motion. The leaflets become ‘tethered’ or ‘restricted’ from fully coapting, creating a central regurgitant jet, often described as a ‘tenting’ of the leaflets. This is further exacerbated by annular dilation. (frontiersin.org)
• Clinical Implications: Ischemic MVR can worsen heart failure symptoms, contribute to recurrent hospitalizations, and negatively impact long-term prognosis, even after revascularization. Its severity often correlates with the extent of LV dysfunction and remodeling.

3.2.2 Dilated Cardiomyopathy (DCM)

DCM, whether ischemic or non-ischemic in origin (e.g., idiopathic, viral, toxic, familial), is characterized by global dilation and systolic dysfunction of the left ventricle. This widespread ventricular remodeling is a primary driver of secondary MVR.

• Pathology: The profound enlargement of the left ventricle directly leads to:
  • Annular Dilation: The mitral annulus, particularly its posterior and lateral segments, stretches significantly due to the expanding ventricular base. This increases the circumference of the valve opening, making it difficult for the leaflets to span the gap.
  • Papillary Muscle Displacement: Similar to ischemic MVR, the global dilation of the LV causes the papillary muscles to be displaced laterally and apically.
  • Leaflet Tethering: The displaced papillary muscles pull on the chordae tendineae, tethering the leaflets and preventing proper coaptation. In DCM, the tethering is often more symmetrical compared to ischemic MVR, which can be more localized. The leaflets, although structurally normal, cannot meet in the center of the valve during systole, resulting in a central regurgitant jet. (kardio.hr)
• Clinical Implications: Functional MVR in DCM exacerbates volume overload, increases ventricular wall stress, and accelerates the progression of heart failure. It is a significant predictor of adverse outcomes in patients with DCM. The severity of MVR often fluctuates with changes in LV loading conditions and medical therapy.

3.2.3 Other Causes of Secondary MVR

• Hypertrophic Cardiomyopathy (HCM): In obstructive HCM, the hypertrophied interventricular septum can cause systolic anterior motion (SAM) of the mitral anterior leaflet, pulling it into the left ventricular outflow tract. This movement prevents proper leaflet coaptation with the posterior leaflet, leading to MVR. The regurgitant jet is often directed posteriorly.
• Restrictive Cardiomyopathy: While less common, certain forms of restrictive cardiomyopathy can lead to LV architectural distortion and secondary MVR.
• Severe Annular Calcification (MAC): Extensive calcification of the mitral annulus, particularly common in elderly patients with chronic kidney disease, can prevent proper annular contraction and leaflet excursion, leading to MVR. It also poses a significant challenge for surgical and transcatheter interventions. (mdpi.com)

3.3 Hemodynamic Consequences of MVR

Regardless of its etiology, chronic MVR imposes a significant hemodynamic burden on the heart, initiating a vicious cycle of compensatory mechanisms that eventually lead to myocardial dysfunction and heart failure.

• Volume Overload: During ventricular systole, a portion of the LV stroke volume is ejected into the low-pressure left atrium (regurgitant volume) instead of entirely into the high-pressure aorta (forward stroke volume). To maintain adequate forward cardiac output, the left ventricle must increase its total stroke volume. This chronic increase in preload leads to LV eccentric hypertrophy and progressive dilation.
• Left Atrial Dilation and Pulmonary Hypertension: The increased volume and pressure in the left atrium lead to its progressive dilation. This can stretch the pulmonary veins, causing pulmonary venous hypertension, which, if sustained, can progress to pulmonary arterial hypertension, leading to right ventricular dysfunction. Left atrial enlargement also significantly increases the risk of atrial fibrillation, a common comorbidity that further compromises cardiac output and complicates management.
• Progressive LV Dysfunction: While eccentric hypertrophy initially serves as a compensatory mechanism, allowing the LV to handle the increased volume, prolonged volume overload eventually leads to myocardial fibrosis, maladaptive remodeling, and intrinsic contractile dysfunction. The ejection fraction (EF), initially normal or even supranormal in severe chronic MVR due to the low afterload imposed by the regurgitant orifice, can deceptively appear preserved even when the ventricle is beginning to fail. A decrease in EF below 60% or an increase in left ventricular end-systolic dimension (LVESD) beyond 40 mm are established indicators of impending LV contractile failure and often trigger for intervention in asymptomatic primary MVR.
• Increased Wall Stress: The dilated ventricle experiences increased wall stress (Laplace’s Law), which further contributes to myocardial damage and exacerbates dilation. This forms a positive feedback loop that accelerates ventricular remodeling and heart failure progression.

Understanding these distinct pathophysiological pathways is critical for accurate diagnosis, appropriate risk stratification, and the selection of the most effective and timely therapeutic interventions for patients with MVR.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

4. Epidemiology

Mitral Valve Regurgitation is indeed the most prevalent valvular heart disease globally, affecting millions of individuals and representing a substantial public health burden. Its epidemiology is dynamic, influenced by geographical location, age demographics, socioeconomic factors, and the prevalence of underlying cardiac conditions.

4.1 Global Prevalence and Incidence

Estimates suggest that MVR affects over 2 million individuals in the United States alone, with a projected increase given the aging population. The overall prevalence of moderate or severe MVR in the general adult population is estimated to be around 2-3%. However, this figure rises significantly with age, affecting approximately 10% of individuals over 75 years old. This age-related increase is largely attributable to the rising incidence of degenerative valve disease and ischemic heart disease. (pubmed.ncbi.nlm.nih.gov)

4.2 Distribution of Primary vs. Secondary MVR

The relative proportions of primary and secondary MVR vary considerably across different geographical regions and socioeconomic strata:

• Developed Countries: In North America and Western Europe, primary (degenerative) MVR, primarily due to mitral valve prolapse and fibroelastic deficiency, accounts for the majority of severe MVR cases requiring intervention. Improved living standards and access to healthcare have drastically reduced the incidence of rheumatic heart disease. Consequently, the elderly population in these regions frequently presents with MVR secondary to age-related degenerative changes, often alongside ischemic or dilated cardiomyopathy.
• Developing Countries: In contrast, developing countries, particularly in sub-Saharan Africa, parts of Asia, and Latin America, continue to bear a disproportionately high burden of rheumatic heart disease. Here, rheumatic MVR, often coexisting with mitral stenosis, remains a leading cause of severe valvular heart disease, affecting younger populations. However, with the increasing prevalence of cardiovascular risk factors and improved longevity, secondary MVR due to ischemic heart disease and dilated cardiomyopathy is also on the rise in these regions.

4.3 Impact of Aging Populations

The global demographic shift towards an older population significantly contributes to the rising prevalence of MVR. As individuals age, the mitral valve apparatus undergoes degenerative changes, including myxomatous degeneration, annular calcification, and fibrosis, which can predispose to primary MVR. Concurrently, the increasing incidence of coronary artery disease, hypertension, and diabetes in older adults leads to a higher prevalence of ischemic heart disease and dilated cardiomyopathy, thereby increasing the burden of secondary MVR. This demographic trend poses significant challenges for healthcare systems, necessitating expanded resources for diagnostic evaluation and therapeutic interventions.

4.4 Economic Burden

MVR, especially when severe and symptomatic, places a substantial economic burden on healthcare systems. This includes costs associated with prolonged hospital stays for heart failure exacerbations, repeated diagnostic imaging, complex surgical and transcatheter interventions, long-term medical management, and rehabilitation. The indirect costs, such as lost productivity due to disability, further amplify the overall economic impact. Effective and timely management strategies are crucial not only for improving patient outcomes but also for mitigating the economic strain associated with this prevalent condition.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

5. Clinical Presentation and Diagnostic Techniques

Accurate diagnosis and comprehensive assessment of MVR are critical steps in guiding management. This involves a combination of clinical evaluation, sophisticated imaging modalities, and, at times, invasive hemodynamic assessment. The clinical presentation of MVR can vary widely, from asymptomatic to overt heart failure, largely depending on the severity, chronicity, and underlying etiology of the regurgitation.

5.1 Clinical Presentation

Patients with MVR can remain asymptomatic for many years, even with severe regurgitation, particularly in chronic primary MVR where the left ventricle has had time to adapt. However, symptoms often develop as the compensatory mechanisms fail, or when MVR occurs acutely.

• Dyspnea: The most common symptom, initially exertional dyspnea, progressing to orthopnea and paroxysmal nocturnal dyspnea as pulmonary congestion worsens due to elevated left atrial and pulmonary pressures.
• Fatigue and Weakness: Resulting from reduced forward cardiac output, especially during exertion.
• Palpitations: Often due to left atrial enlargement predisposing to atrial fibrillation, or ectopic beats.
• Peripheral Edema: A sign of advanced heart failure and systemic congestion.
• Chest Pain: Less common, but can occur, particularly in ischemic MVR.
• Acute MVR: In cases of acute severe MVR (e.g., due to papillary muscle rupture post-MI or endocarditic chordal rupture), patients often present with sudden onset of severe dyspnea, pulmonary edema, hypotension, and cardiogenic shock, requiring emergent medical and surgical intervention.

5.2 Physical Examination

Physical examination findings can provide important clues to the presence and severity of MVR:

• Holosystolic Murmur: The classic finding is a high-pitched, blowing holosystolic (pansystolic) murmur, best heard at the apex and radiating to the axilla. In primary MVR, a softer murmur with an apical thrill might be noted. In secondary MVR, the murmur might be less intense and more centrally located.
• Third Heart Sound (S3): A distinct S3 gallop, heard during early diastole, indicates significant volume overload and ventricular dysfunction.
• Apical Impulse: A hyperdynamic, laterally displaced apical impulse suggests left ventricular dilation and volume overload.
• Signs of Pulmonary Hypertension: A palpable right ventricular heave, loud P2 (pulmonic component of S2), and jugular venous distention may be present in advanced cases.
• Signs of Heart Failure: Crackles (rales) in the lung bases, peripheral edema, hepatomegaly, and ascites indicate advanced heart failure.

5.3 Advanced Diagnostic Imaging Modalities

Precise and detailed imaging is indispensable for confirming the diagnosis, quantifying MVR severity, determining its etiology, assessing ventricular function, and guiding therapeutic decisions.

5.3.1 Echocardiography

Echocardiography is the cornerstone of MVR diagnosis and assessment, offering non-invasive, real-time visualization of cardiac structures and blood flow dynamics.

• Transthoracic Echocardiography (TTE): As the first-line diagnostic tool, TTE provides comprehensive information on:
  • Valve Morphology: Visualizes leaflet thickening, prolapse, flail segments, chordal rupture, vegetations, and annular calcification, helping to distinguish primary from secondary MVR.
  • Regurgitant Jet Characteristics: Doppler echocardiography visualizes the regurgitant jet, allowing for qualitative assessment of its size, direction, and velocity. The color flow Doppler allows estimation of the jet’s width and penetration into the left atrium.
  • Quantification of Severity: Advanced Doppler techniques are used to quantify MVR severity. Key parameters include:
    • Vena Contracta Width: The narrowest part of the regurgitant jet, correlating with regurgitant orifice size. A width ≥ 7 mm typically indicates severe MVR.
    • Proximal Isovelocity Surface Area (PISA) Method: A semi-quantitative method that estimates the effective regurgitant orifice area (EROA) and regurgitant volume (RVol) by analyzing the converging flow acceleration proximal to the regurgitant orifice. EROA ≥ 40 mm² or RVol ≥ 60 mL per beat usually defines severe primary MVR; for secondary MVR, slightly lower thresholds (EROA ≥ 20 mm², RVol ≥ 30 mL/beat) may indicate severe disease due to its poorer prognosis.
    • Pulmonary Vein Flow: Blunted or reversed systolic flow in pulmonary veins indicates severe regurgitation and elevated left atrial pressure.
  • Ventricular Function and Dimensions: Assesses left ventricular ejection fraction (LVEF), end-systolic and end-diastolic dimensions (LVESD, LVEDD), and signs of chamber remodeling. It also evaluates right ventricular function and estimates pulmonary artery pressures. (ncbi.nlm.nih.gov)
• Transesophageal Echocardiography (TEE): Offers superior image quality due to the absence of lung and bone interference, particularly useful in obese patients or those with poor acoustic windows on TTE. TEE is invaluable for:
  • Detailed Anatomical Assessment: Provides exquisite detail of leaflet pathology (e.g., identifying specific scallops involved in prolapse, precise location of perforations, chordal rupture), crucial for surgical planning.
  • Intraoperative Guidance: Essential for guiding transcatheter mitral valve interventions (e.g., MitraClip, transcatheter annuloplasty, TMVR) and assessing their immediate results.
  • Exclusion of Endocarditis: High sensitivity for detecting vegetations in infective endocarditis. (medtechnews.uk)
• Three-Dimensional Echocardiography (3D Echo): Provides comprehensive, anatomically precise visualization of the entire mitral valve apparatus. It is increasingly used for:
  • Pre-procedural Planning: Creates detailed en face views of the mitral valve, aiding in assessing repair feasibility and guiding transcatheter interventions. It offers accurate measurements of annular dimensions, leaflet area, and coaptation depth.
  • Improved Quantification: Allows for more accurate and reproducible quantification of EROA and regurgitant volume compared to 2D methods, particularly for complex or eccentric jets. (arxiv.org)

5.3.2 Cardiac Magnetic Resonance Imaging (MRI)

Cardiac MRI is emerging as a powerful tool for MVR assessment, particularly valuable when echocardiographic images are suboptimal or when highly accurate quantitative data are required.

• Advantages:
  • Precise Quantification: Considered the gold standard for quantifying LV volumes, mass, and function, independent of geometric assumptions. It accurately quantifies regurgitant volume and regurgitant fraction using phase-contrast velocity mapping, which is less susceptible to errors associated with eccentric jets.
  • Tissue Characterization: Late gadolinium enhancement (LGE) imaging can detect myocardial fibrosis (scarring), which is prognostically significant in both ischemic and non-ischemic cardiomyopathy and informs decisions in secondary MVR.
  • Comprehensive Assessment: Provides detailed anatomical and functional information about the mitral valve and surrounding structures, including the left atrium, pulmonary veins, and right ventricle, offering a broader perspective on how MVR affects overall cardiac health. (medtechnews.uk)

5.3.3 Computed Tomography (CT)

Cardiac CT has a more specialized role in MVR, primarily in the context of transcatheter interventions.

• Pre-procedural Planning for TMVR: CT is essential for:
  • Annular Sizing: Precise measurement of the mitral annulus dimensions and morphology.
  • Assessment of Calcification: Identifying and characterizing mitral annular calcification (MAC), which can significantly impact implant feasibility and increase risks.
  • LVOT Obstruction Risk: Evaluating the risk of left ventricular outflow tract (LVOT) obstruction after transcatheter mitral valve replacement by assessing the relationship between the mitral annulus, ventricular septum, and aortic valve.
  • Vascular Access Planning: Visualizing the access vessels (e.g., femoral vein, transseptal route) for transcatheter delivery systems.

5.3.4 Cardiac Catheterization

While largely superseded by non-invasive imaging for diagnosis, cardiac catheterization retains specific roles:

• Coronary Angiography: Essential for assessing coexisting coronary artery disease, particularly prior to surgical interventions, given the high prevalence of ischemic heart disease in MVR patients.
• Hemodynamic Assessment: Can provide precise measurements of left atrial pressure (v-wave morphology), pulmonary artery pressures, and cardiac output, especially when non-invasive findings are discordant or when evaluating patients with complex hemodynamics.
• Differential Diagnosis: In certain cases, to exclude other causes of pulmonary hypertension.

5.3.5 Biomarkers

Biomarkers, particularly N-terminal pro-B-type natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP), serve as indicators of cardiac stretch and stress. Elevated levels correlate with MVR severity, left ventricular dysfunction, and prognosis. While not diagnostic of MVR, they can be useful for risk stratification, monitoring disease progression, and assessing the effectiveness of therapy, especially in asymptomatic patients or those with secondary MVR. (pubmed.ncbi.nlm.nih.gov)

The integration of clinical assessment with these advanced diagnostic tools allows for a comprehensive understanding of each patient’s MVR, enabling tailored management strategies and optimal timing of intervention.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

6. Treatment Modalities

The management of MVR is highly individualized, depending on the severity of regurgitation, the presence and severity of symptoms, the underlying etiology (primary vs. secondary), the degree of left ventricular dysfunction and remodeling, and the patient’s overall surgical risk profile. Treatment options range from conservative medical management to complex surgical and transcatheter interventions.

6.1 Medical Management

Medical therapy for MVR is primarily supportive and aims to alleviate symptoms, prevent disease progression, and manage comorbidities. It is the mainstay for asymptomatic patients with non-severe MVR, and a crucial adjunct for all patients, even those undergoing interventional therapies.

6.1.1 Pharmacological Therapy

• Diuretics: Medications such as furosemide or hydrochlorothiazide are used to manage symptoms of fluid overload, such as dyspnea and peripheral edema, by reducing preload and pulmonary congestion.
• Vasodilators (ACE Inhibitors, ARBs, Hydralazine): In patients with secondary MVR and LV dysfunction, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) can reduce afterload, thereby reducing the regurgitant volume and improving forward stroke volume. This strategy is less effective and not routinely recommended in asymptomatic primary MVR with normal LV function, as it may paradoxically increase regurgitation by reducing systemic blood pressure more than it improves forward flow. In specific cases of severe, symptomatic MVR with contraindications to surgery, vasodilators like hydralazine may be considered.
• Beta-Blockers: Primarily used in secondary MVR (e.g., in the context of ischemic heart disease or dilated cardiomyopathy) to improve LV function, reduce heart rate, and mitigate harmful neurohormonal activation. They are also vital for rate control in atrial fibrillation.
• Aldosterone Antagonists: Spironolactone or eplerenone are often added to medical regimens in patients with heart failure with reduced ejection fraction, including those with secondary MVR, to improve outcomes and reduce remodeling.
• Digoxin: May be used for rate control in patients with atrial fibrillation and severe LV dysfunction.

6.1.2 Management of Underlying Conditions

Effective management of comorbidities is crucial:

• Atrial Fibrillation (AF): AF is a common complication of MVR due to left atrial dilation. Management includes anticoagulation to prevent stroke (based on CHA2DS2-VASc score), and rate or rhythm control strategies (e.g., cardioversion, antiarrhythmic drugs, ablation) to optimize cardiac output.
• Hypertension: Strict blood pressure control is essential to reduce afterload and prevent further ventricular remodeling, particularly important in secondary MVR.
• Coronary Artery Disease (CAD): In patients with ischemic MVR, optimal medical therapy for CAD, including antiplatelet agents and statins, and consideration of revascularization (PCI or CABG) is critical to improve myocardial function and potentially reduce MVR severity.

6.2 Surgical Interventions

Surgical intervention remains the gold standard for definitive treatment of severe MVR, particularly in primary MVR. The choice between repair and replacement depends on the specific valve pathology, surgical expertise, and patient characteristics.

6.2.1 Mitral Valve Repair (MVRp)

Mitral valve repair is generally preferred over replacement whenever anatomically feasible, especially for primary MVR, due to superior long-term outcomes, better preservation of LV function, lower rates of endocarditis, and avoidance of lifelong anticoagulation (if sinus rhythm is maintained). The fundamental principle of repair is to restore normal leaflet coaptation and valve competence. Techniques are highly individualized and often combine several approaches:

• Annuloplasty: This is a cornerstone of most mitral valve repairs. A prosthetic ring (flexible, rigid, partial, or complete) is implanted around the mitral annulus to reduce its size and stabilize its shape, thereby facilitating leaflet coaptation. Annuloplasty counteracts annular dilation, which is often present even in primary MVR. (msdmanuals.com)
• Leaflet Resection/Plication: For redundant or prolapsing leaflet segments (e.g., in fibroelastic deficiency), the excessive tissue can be resected (quadrangular resection) and the remaining leaflet edges sutured together (plication) to reduce prolapse.
• Chordal Replacement/Transposition: Elongated or ruptured chordae can be replaced with artificial GORE-TEX (polytetrafluoroethylene) sutures, which mimic natural chordae, or healthy chordae from an adjacent non-prolapsing segment can be transposed. This technique is particularly effective for flail leaflets.
• Commissurotomy/Decalcification: In rheumatic MVR, surgical commissurotomy can separate fused commissures, and decalcification can improve leaflet mobility, though repair is often more challenging in these complex cases.
• Minimally Invasive and Robotic Surgery: Advancements in surgical techniques allow for mitral valve repair through smaller incisions (e.g., right minithoracotomy) or robotically, potentially offering benefits such as reduced pain, faster recovery, and improved cosmesis, though requiring specialized expertise.

6.2.2 Mitral Valve Replacement (MVRx)

Mitral valve replacement is indicated when repair is not technically feasible or when the valve is severely damaged (e.g., extensive calcification, severe rheumatic damage, multiple flail segments, or failed previous repair). The choice of prosthetic valve depends on patient age, lifestyle, and willingness to take anticoagulation:

• Mechanical Prosthetic Valves: Highly durable, offering excellent longevity (typically 20-30 years or more). However, they require lifelong anticoagulation with warfarin due to their thrombogenicity, carrying risks of bleeding and thromboembolism. Patients also experience an audible ‘click’. They are generally favored for younger patients (e.g., <60-65 years) without contraindications to anticoagulation.
• Bioprosthetic (Tissue) Valves: Constructed from animal tissue (porcine or bovine pericardium), these valves have a lower risk of thromboembolism and typically do not require lifelong anticoagulation (short-term anticoagulation may be used post-surgery). Their main limitation is structural valve degeneration over time (calcification, tearing), necessitating re-intervention (surgical or transcatheter) within 10-15 years, on average. They are generally preferred for older patients or those with contraindications to anticoagulation.
• Valve-in-Valve Procedures: For patients with degenerated bioprosthetic valves who are high-risk for reoperation, transcatheter aortic valve replacement (TAVR) technology has been adapted to implant a new transcatheter valve within the degenerated surgical bioprosthesis, avoiding open-heart surgery.

6.3 Transcatheter Therapies

Transcatheter interventions represent a rapidly evolving field, offering less invasive treatment options for patients deemed high-risk or ineligible for conventional surgery. These procedures are typically performed in hybrid operating rooms by multidisciplinary Heart Teams.

6.3.1 Transcatheter Edge-to-Edge Repair (TEER)

TEER, exemplified by the MitraClip and PASCAL systems, is the most established transcatheter therapy for MVR. It aims to reduce regurgitation by approximating the anterior and posterior mitral leaflets in the middle, creating a ‘double orifice’ valve, similar to the surgical Alfieri stitch.

• Mechanism: A catheter-delivered device grasps the free edges of the anterior and posterior mitral leaflets, effectively clipping them together. This improves leaflet coaptation and reduces the regurgitant orifice.
• Indications:
  • Severe Primary MVR: Indicated for symptomatic patients with severe primary MVR who are considered high-risk for conventional surgery due to comorbidities or advanced age.
  • Severe Secondary MVR: Indicated for symptomatic patients with severe secondary MVR despite optimal guideline-directed medical therapy (GDMT), who have suitable anatomy and remain high-risk for surgery. The COAPT trial demonstrated a significant reduction in heart failure hospitalizations and mortality in this specific subgroup of patients. (msdmanuals.com)
• Advantages: Less invasive, shorter recovery time, no cardiopulmonary bypass.
• Limitations: May not achieve complete abolition of MVR, potential for residual regurgitation, not suitable for all anatomies (e.g., severe annular calcification, very large coaptation gaps, restrictive leaflet motion).

6.3.2 Transcatheter Annuloplasty

These devices aim to reduce annular dilation and improve leaflet coaptation, primarily targeting secondary MVR.

• Indirect Annuloplasty (e.g., Carillon system): A device is implanted in the coronary sinus, which is anatomically close to the mitral annulus. Shortening the device indirectly cinches the annulus, reducing its circumference.
• Direct Annuloplasty (e.g., Cardioband system): A band is implanted directly onto the mitral annulus via a transseptal approach, and then cinched to reduce annular size. This technique remodels the annulus, similar to surgical annuloplasty.
• Indications: Primarily for severe symptomatic secondary MVR in high-risk patients.
• Challenges: The coronary sinus approach can be limited by anatomical variations (e.g., small coronary sinus diameter), and direct annuloplasty requires more complex transseptal access and anchoring.

6.3.3 Transcatheter Mitral Valve Replacement (TMVR)

TMVR is an emerging and highly complex field, offering a complete valve replacement via a catheter-based approach. It is primarily being developed for patients with severe MVR who are deemed non-operable or extremely high-risk for surgery.

• Types of TMVR:
  • Valve-in-Valve/Valve-in-Ring: Implantation of a transcatheter valve within a degenerated surgical bioprosthetic valve or annuloplasty ring. This is the most straightforward TMVR procedure.
  • Native Valve TMVR: Implantation of a transcatheter valve into the native mitral annulus. This is significantly more challenging due to the complex, non-circular, and dynamic anatomy of the native mitral annulus, and the risk of left ventricular outflow tract (LVOT) obstruction from the new valve frame.
• Access Routes: Transseptal (via femoral vein, through the interatrial septum) or transapical (direct puncture of the LV apex).
• Current Status: Several devices are undergoing clinical trials. While promising for very high-risk patients, it faces significant anatomical and technical hurdles, including optimal anchoring, avoiding LVOT obstruction, and managing paravalvular leaks.

6.3.4 Transcatheter Chordal Replacement Systems

These are experimental systems that aim to replicate surgical chordal replacement by implanting artificial chordae via a transapical or transseptal approach, typically for primary MVR with prolapse or flail leaflets. Devices like the NeoChord system are showing early promise in selected patients, offering a less invasive alternative to open-heart surgery for specific pathologies.

The selection of the most appropriate treatment modality requires a detailed assessment by a multidisciplinary Heart Team, weighing the benefits, risks, and long-term implications of each option against the patient’s individual clinical profile and valve anatomy.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

7. Patient Selection Criteria and Timing of Intervention

Optimal outcomes for patients with MVR are intrinsically linked to careful patient selection and precise timing of intervention. The decision-making process is complex, requiring a multidisciplinary Heart Team approach that integrates clinical symptoms, MVR severity, left ventricular function and remodeling, patient comorbidities, and anatomical suitability for various procedures. Current guidelines from major cardiology societies (e.g., ACC/AHA, ESC) provide a framework, but individualized assessment remains paramount.

7.1 Key Principles of Patient Selection

• Shared Decision-Making: The process involves detailed discussions with the patient and their family, explaining the risks and benefits of all available options, considering their preferences, values, and quality-of-life goals.
• Multidisciplinary Heart Team: Essential for complex cases, comprising cardiac surgeons, interventional cardiologists, imaging specialists, heart failure specialists, and anesthesiologists. This team evaluates all clinical and imaging data to determine the most appropriate strategy.
• Risk-Benefit Assessment: Thorough evaluation of the patient’s surgical risk, comorbidities, and frailty (e.g., using STS score, EuroSCORE II, or comprehensive geriatric assessment) is crucial, as higher surgical risk may favor less invasive transcatheter approaches. (pmc.ncbi.nlm.nih.gov)

7.2 Indications for Intervention in Primary MVR

Primary MVR, particularly severe forms, generally has clearer indications for intervention due to the direct valve pathology. Intervention aims to prevent irreversible LV dysfunction and heart failure.

• Severe Symptomatic MVR: All symptomatic patients (NYHA Class II, III, or IV) with severe primary MVR should be considered for intervention, regardless of LV function, provided they are reasonable surgical candidates. Repair is preferred over replacement.
• Asymptomatic Severe MVR with LV Dysfunction: Intervention is strongly recommended for asymptomatic patients with severe primary MVR and objective evidence of left ventricular dysfunction, defined as:
  • Left Ventricular Ejection Fraction (LVEF) < 60%.
  • Left Ventricular End-Systolic Dimension (LVESD) ≥ 40 mm.
    These parameters indicate early ventricular decompensation and predict adverse outcomes if left untreated, even in the absence of symptoms.
• Asymptomatic Severe MVR with New Onset Atrial Fibrillation: For asymptomatic patients with severe primary MVR who develop new-onset atrial fibrillation not attributable to other causes, intervention is recommended to potentially restore sinus rhythm and prevent further LA and LV remodeling.
• Asymptomatic Severe MVR with Pulmonary Hypertension: Development of pulmonary hypertension (systolic pulmonary artery pressure > 50 mmHg at rest or > 60 mmHg with exercise) in an asymptomatic patient with severe primary MVR is another indicator for intervention, as it suggests significant hemodynamic consequences.
• High Probability of Successful Durable Repair: In selected cases of asymptomatic severe primary MVR with preserved LV function, early surgery by an experienced surgeon (with a high likelihood of successful and durable repair, i.e., >95% success and low operative mortality <1%) may be considered, often referred to as ‘early referral’ or ‘prophylactic’ surgery, to prevent the onset of symptoms or LV dysfunction.
• Endocarditis: For severe MVR due to infective endocarditis, urgent or emergent surgical intervention may be required if there is persistent infection, large vegetations with embolic risk, heart failure, or perivalvular extension of infection.

7.3 Indications for Intervention in Secondary MVR

Indications for intervention in secondary MVR are more nuanced and generally reserved for symptomatic patients, as the primary problem lies with the underlying myocardial disease rather than the valve itself. Medical therapy for heart failure is the first line of treatment.

• Severe Symptomatic MVR Despite Optimal Medical Therapy: Intervention may be considered for patients with severe symptomatic secondary MVR (NYHA Class II, III, or IV) despite maximal guideline-directed medical therapy (GDMT) for heart failure (including ACE inhibitors/ARBs, beta-blockers, aldosterone antagonists, and CRT if indicated).
  • Surgical Repair (Annuloplasty): Surgical annuloplasty is often performed concurrently with coronary artery bypass grafting (CABG) in patients with ischemic MVR requiring revascularization. Its efficacy as a standalone procedure for severe secondary MVR is debated, with some studies showing limited long-term benefits on mortality compared to GDMT alone, particularly in patients with advanced LV dysfunction.
  • Transcatheter Edge-to-Edge Repair (TEER): The COAPT trial provided strong evidence for TEER (MitraClip) in select patients with severe symptomatic secondary MVR who remain symptomatic despite optimal GDMT and have suitable anatomy. It demonstrated a significant reduction in heart failure hospitalizations and mortality in this specific population. Key criteria included LVEF between 20-50%, LVESD ≤ 70 mm, and pulmonary artery systolic pressure ≤ 70 mmHg.
• Anatomical Suitability for TEER: Patients must have valve anatomy suitable for TEER (e.g., leaflet morphology, coaptation depth, coaptation length, absence of extensive calcification) as assessed by echocardiography.
• Patient Goals: The primary goal of intervention in secondary MVR is typically symptom relief and improvement in quality of life rather than prolonged survival, though COAPT data suggest a survival benefit in carefully selected patients.

7.4 Anatomical Suitability and Risk Assessment for Transcatheter Therapies

For transcatheter interventions, meticulous pre-procedural imaging and patient selection are critical:

• Anatomical Criteria for TEER: Detailed echocardiographic assessment (TEE) is essential to evaluate leaflet thickness, mobility, presence of significant calcification, coaptation gap, regurgitant jet characteristics, and the feasibility of grasping both leaflets. The absence of specific ‘unfavorable anatomies’ (e.g., very large coaptation gaps, extremely calcified leaflets, or rheumatic pathology) is crucial.
• Surgical Risk Assessment: For all patients considered for intervention, a comprehensive assessment of comorbidities, frailty, and predicted surgical mortality (using scores like STS score or EuroSCORE II) is performed. Patients with high surgical risk (e.g., predicted operative mortality >8-10%) are often candidates for transcatheter approaches if anatomically suitable. However, even for transcatheter procedures, patients must be expected to survive for a reasonable period and benefit from the intervention (e.g., expected survival >1 year).
• Heart Team Discussion: Every patient considered for intervention, particularly those with complex secondary MVR or high surgical risk, should be discussed by a multidisciplinary Heart Team to determine the optimal treatment strategy, whether it be surgical repair/replacement, a transcatheter procedure, or continued medical therapy with palliative care considerations.

The timing of intervention in MVR is a dynamic decision that balances the risks of surgery/intervention against the risks of delaying treatment and allowing progressive LV dysfunction. Adherence to established guidelines, coupled with expert multidisciplinary assessment, leads to the best possible patient outcomes.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

8. Long-Term Outcomes, Quality of Life, and Follow-up

Long-term outcomes in MVR patients are significantly influenced by the timing and type of intervention, the underlying etiology, and the patient’s baseline characteristics. The overarching goals of MVR treatment are to alleviate symptoms, prevent the progression of LV dysfunction, improve functional capacity, enhance quality of life, and ultimately prolong survival. Post-procedural surveillance is essential to monitor for potential complications and recurrence of regurgitation.

8.1 Survival Rates

• Primary MVR: Surgical repair of severe primary MVR, especially when performed early in asymptomatic patients with preserved LV function, is associated with excellent long-term survival rates, often comparable to that of the general population. Studies have shown that surgical repair can reduce mortality by approximately 70% compared to medical management for severe primary MVR. Timely intervention before the onset of irreversible LV dysfunction (LVEF < 60% or LVESD > 40 mm) is crucial for maximizing survival benefit. Long-term studies report 10-year survival rates exceeding 70-80% after successful repair. (pubmed.ncbi.nlm.nih.gov)
• Secondary MVR: The prognosis for secondary MVR is primarily dictated by the severity of the underlying left ventricular dysfunction. While medical therapy is foundational, selected patients undergoing intervention can see improved outcomes. The COAPT trial, for instance, demonstrated that TEER significantly reduced mortality and heart failure hospitalizations in carefully selected patients with severe symptomatic secondary MVR despite optimal guideline-directed medical therapy over a 2-year follow-up period. Surgical repair for secondary MVR, often performed in conjunction with CABG, has shown mixed results regarding long-term survival benefit as a standalone treatment for MVR, compared to medical management alone in some trials.
• Transcatheter vs. Surgical Outcomes: For primary MVR, surgical repair remains the benchmark, particularly in lower-risk patients with suitable anatomy for durable repair. Transcatheter therapies like TEER offer a viable and effective alternative for high-surgical-risk primary MVR patients, providing significant clinical benefit, though long-term comparative data on survival and durability against surgery are still evolving.

8.2 Quality of Life and Functional Status

Both surgical and transcatheter interventions for severe MVR are consistently associated with significant improvements in patient-reported quality of life and functional status.

• Symptom Relief: Patients typically experience a marked reduction in symptoms of heart failure, such as dyspnea and fatigue, leading to an improvement in New York Heart Association (NYHA) functional class. This allows patients to participate in activities that were previously limited due to their heart condition.
• Exercise Capacity: Objective measures of exercise capacity, such as those assessed by treadmill tests or 6-minute walk tests, often show significant improvement post-intervention.
• Overall Well-being: Reduced hospitalizations for heart failure exacerbations, increased independence, and the ability to engage in social and recreational activities all contribute to a better overall quality of life. This is particularly impactful for patients who were severely symptomatic prior to intervention.

8.3 Recurrence of Regurgitation

Despite successful initial intervention, the long-term risk of recurrence of MVR remains a concern, varying by etiology and procedure:

• Surgical Repair for Primary MVR: Surgical repair for primary MVR, especially when performed by experienced surgeons, typically boasts excellent long-term durability. Recurrence rates of moderate-to-severe MVR are generally low (around 5-10% at 10 years) but depend on the specific pathology (e.g., fibroelastic deficiency tends to have more durable repairs than Barlow’s disease). Reoperation rates are correspondingly low.
• Surgical Repair for Secondary MVR: Recurrence of MVR after surgical repair for secondary MVR (typically annuloplasty) is unfortunately higher, with reported rates of moderate-to-severe regurgitation reaching 20-30% or more at 5 years. This higher recurrence is due to the progressive nature of the underlying left ventricular disease and ongoing ventricular remodeling, which can negate the initial effect of annuloplasty.
• Transcatheter Edge-to-Edge Repair (TEER): TEER devices have demonstrated durable reduction in MVR in primary MVR patients out to 5 years, with low re-intervention rates. For secondary MVR, while the initial reduction in regurgitation is significant, some degree of residual or recurrent MVR can occur over time, particularly in patients with progressive LV dilation or adverse remodeling, though the COAPT trial showed sustained benefit over 2 years. (msdmanuals.com)

8.4 Valve-Related Complications

Long-term follow-up also necessitates monitoring for potential valve-related complications:

• Thromboembolism: Risk is highest with mechanical prosthetic valves, requiring lifelong anticoagulation. Bioprosthetic valves and TEER devices have lower risks but still require careful monitoring.
• Infective Endocarditis: Patients with prosthetic valves or a history of endocarditis are at increased risk and require prophylactic antibiotics for certain procedures.
• Structural Valve Degeneration (SVD): Primarily a concern with bioprosthetic valves, leading to valve stenosis or regurgitation over time and necessitating re-intervention.
• Bleeding Complications: Associated with anticoagulant therapy for mechanical valves or atrial fibrillation.
• Paravalvular Leak: Inadequate sealing around prosthetic valves or annuloplasty rings can lead to persistent regurgitation.

8.5 Long-Term Follow-up Strategy

Regular and structured follow-up is essential for all MVR patients, especially after intervention. This typically includes:

• Clinical Assessment: Routine visits to monitor symptoms, functional status, and medication adherence.
• Echocardiographic Surveillance: Periodic transthoracic echocardiograms (e.g., annually for stable patients, more frequently if concerns arise) to assess valve function, MVR severity, LV dimensions and function, and pulmonary pressures.
• Laboratory Tests: Monitoring for kidney function, electrolyte balance (especially with diuretic use), and INR for anticoagulated patients.
• Management of Comorbidities: Continued optimization of medical therapy for heart failure, hypertension, atrial fibrillation, and coronary artery disease.

Through meticulous patient selection, timely intervention, and comprehensive long-term follow-up, the management of MVR aims to maximize survival, improve quality of life, and mitigate the progression of this challenging heart condition. The evolving landscape of transcatheter therapies continues to expand options for patients previously considered untreatable, offering new hope for improved outcomes.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

9. Emerging Technologies and Future Directions

The field of Mitral Valve Regurgitation diagnosis and treatment is one of rapid innovation, driven by a deeper understanding of its pathophysiology and the unmet needs of patients ineligible for conventional surgery. Future directions will likely focus on enhancing precision in diagnosis, expanding the armamentarium of less invasive therapies, and tailoring treatments through personalized medicine approaches.

9.1 Advanced Imaging Modalities

• Artificial Intelligence (AI) and Machine Learning in Echocardiography: AI algorithms are being developed to automate and standardize the quantification of MVR severity (e.g., EROA, RVol), improve the detection of subtle anatomical abnormalities, and predict procedural outcomes. This could enhance diagnostic accuracy, reduce inter-observer variability, and streamline pre-procedural planning.
• 4D Flow MRI: This advanced MRI technique allows for comprehensive assessment of blood flow dynamics in three spatial dimensions over time, providing highly accurate, non-invasive quantification of regurgitant volumes and characterization of complex flow patterns within the left atrium and pulmonary veins, offering insights beyond current capabilities.
• Fusion Imaging: Real-time fusion of echocardiographic images with fluoroscopy and CT/MRI data during transcatheter procedures promises to enhance visualization, guide device placement with greater precision, and reduce procedure times and radiation exposure.

9.2 Novel Transcatheter Therapies

While TEER and transcatheter annuloplasty are establishing their roles, the focus is increasingly shifting towards more definitive, less invasive replacements for native mitral valves.

• Next-Generation TMVR Devices: Significant research and development are underway to overcome the challenges of native valve TMVR. New device designs are addressing issues such as optimal anchoring in the complex mitral annulus, prevention of left ventricular outflow tract (LVOT) obstruction, and management of paravalvular leaks. Devices with lower profiles, easier deliverability, and improved anatomical conformability are in clinical trials. The goal is to develop TMVR systems that can be widely applied to a broader range of native mitral valve anatomies.
• Transcatheter Chordal Repair: Beyond the currently available transcatheter edge-to-edge repair, devices designed specifically for transcatheter neo-chord implantation (e.g., NeoChord system) are gaining traction, aiming to replicate the successful techniques of surgical chordal repair for primary MVR through a minimally invasive approach.
• Combined Therapies: Future strategies may involve a combination of transcatheter techniques, such as transcatheter annuloplasty followed by edge-to-edge repair, or even hybrid approaches that blend surgical elements with transcatheter device implantation to achieve optimal results in highly complex cases.

9.3 Personalized Medicine and Patient Stratification

• Genomic and Proteomic Markers: Research is exploring genetic predispositions and circulating biomarkers that can more accurately predict disease progression, identify patients at risk of adverse remodeling, and individualize the timing and type of intervention. This could move towards a more precision-based approach in MVR management.
• Advanced Risk Prediction Models: Incorporating AI and machine learning into traditional risk scores (e.g., STS score) with advanced imaging parameters and biomarker data to provide more precise, individualized predictions of procedural success, complications, and long-term outcomes for specific interventions.
• Enhanced Understanding of Secondary MVR: Further research is needed to better understand the complex interplay between ventricular mechanics, leaflet tethering, and prognosis in secondary MVR. This will refine patient selection for interventions and guide the development of therapies that directly address the underlying myocardial dysfunction.

9.4 Role of Robotics and Virtual Reality

• Robotic-Assisted Surgery: Continues to evolve, offering enhanced dexterity, precision, and visualization for mitral valve repair, potentially expanding the pool of patients eligible for minimally invasive surgical approaches.
• Virtual Reality (VR) and Augmented Reality (AR): These technologies hold promise for surgical and interventional planning, allowing physicians to visualize patient-specific anatomy in 3D, simulate procedures, and practice complex maneuvers before real-time intervention, potentially improving safety and efficacy.

The future of MVR management is poised for transformative advancements that will continue to shift paradigms towards less invasive, more personalized, and highly effective therapies. Collaborative efforts among clinicians, engineers, and researchers will be crucial in translating these innovations into improved patient care and outcomes.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

10. Conclusion

Mitral Valve Regurgitation is a multifaceted and highly prevalent valvular heart disease with diverse etiologies and complex pathophysiological mechanisms. It represents a significant global health challenge, capable of progressing from an asymptomatic state to severe heart failure if left untreated. The distinction between primary (degenerative) MVR, arising from intrinsic valve pathology, and secondary (functional) MVR, resulting from underlying left ventricular dysfunction, is fundamental to understanding its natural history and guiding therapeutic strategies.

Remarkable advancements in diagnostic imaging, particularly echocardiography (including TTE, TEE, and 3D echo) and cardiac MRI, have revolutionized our ability to accurately diagnose MVR, precisely quantify its severity, delineate its etiology, and assess its impact on left ventricular function and remodeling. These detailed assessments are critical for identifying patients at risk and informing intervention decisions.

The therapeutic landscape for MVR has undergone a significant transformation. While guideline-directed medical therapy remains essential for all patients and foundational for secondary MVR, the role of intervention is increasingly prominent. Surgical mitral valve repair stands as the gold standard for severe primary MVR, offering excellent long-term durability and preservation of ventricular function, especially when performed early. When repair is not feasible, surgical replacement provides a definitive solution.

The emergence of transcatheter therapies, particularly transcatheter edge-to-edge repair (TEER), has been a paradigm shift, offering viable, less invasive options for high-surgical-risk patients with both primary and carefully selected cases of severe symptomatic secondary MVR. Emerging technologies such as transcatheter annuloplasty and native valve transcatheter mitral valve replacement hold immense promise for expanding treatment options for even more complex patient populations.

Optimal management of MVR necessitates a highly personalized approach, meticulously considering the severity and etiology of regurgitation, the patient’s symptomatic status, the degree of left ventricular dysfunction, individual comorbidities, surgical risk profile, and anatomical suitability for various interventions. This complex decision-making process is best navigated by a multidisciplinary Heart Team, ensuring that each patient receives the most appropriate and timely intervention.

Looking ahead, the integration of artificial intelligence in diagnostics, the development of next-generation transcatheter devices, and advancements in personalized medicine promise to further refine patient selection, enhance procedural outcomes, and improve the long-term prognosis and quality of life for individuals living with Mitral Valve Regurgitation. The continuous evolution in understanding and treating this condition underscores the dynamic nature of cardiovascular medicine and the relentless pursuit of better patient care.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

References

• en.wikipedia.org
• pubmed.ncbi.nlm.nih.gov
• jcdronline.org
• medtechnews.uk
• arxiv.org
• msdmanuals.com
• pmc.ncbi.nlm.nih.gov
• scivast.com
• kardio.hr
• ncbi.nlm.nih.gov
• pubmed.ncbi.nlm.nih.gov
• frontiersin.org
• kardio.hr
• mdpi.com
• ncbi.nlm.nih.gov
• pubmed.ncbi.nlm.nih.gov
• emedicine.medscape.com