Mitral Valve Disease
Nicholas S. Amoroso
Jessica Atkins
Valerian Fernandes
INTRODUCTION
The mitral valve (MV) regulates blood flow between the left atrium (LA) and left ventricle (LV) of the heart. It is believed to have been popularly named by Andreas Vesalius, who alluded to the leaflet shape that resembles a bishop’s hat: a mitre.1
The MV is composed of two leaflets, an annular perimeter and the subvalvular apparatus that functions in the setting of both low central and high systemic circulatory pressures (see Figure 10.1). The annulus is a saddle-shaped confluence of several cardiac structures including the LA, LV, mitral leaflets, and aortomitral continuity with heterogeneous consistency with both fibrous and nonfibrous tissue components in its plane of leaflet hinge. The subvalvular apparatus includes the chordae tendinae, the papillary muscles, and the LV, to which they are attached.1 Accordingly, abnormalities of the valve leaflets or any of the mitral apparatus components can influence valve function, thereby leading to mitral regurgitation (MR) or mitral stenosis (MS).
Epidemiology
The prevalence of MV disease is difficult to determine from available data sources. Studies documenting any presence of MR report prevalence ranging from 40% to 92%. However, the Framingham Offspring Study reported MR equal to or greater than mild in 19% of women and men.2,3 When focused on moderate to severe MR, the prevalence in Olmstead County, Minnesota was 1.7% in the adult population, and MS affected 0.1% of the population.4 A study of a Chinese population reported that roughly 3% of 133,729 patients undergoing echocardiogram had moderate to severe MR.3 These studies imply that millions of people worldwide suffer from MV disease.
MV disease is very rarely congenital (rate of 5/100,000); it is most commonly acquired secondary to other heart disease.5 MR frequency by etiology varies depending on cohort age, geography, comorbidities, and so on, but degenerative and functional etiologies (see subsequent description) each constitutes 50% of severe MR prevalence.3,4,6
Mitral Stenosis
The incidence of MS is much lower than that of MR, and is related to the prevalence of rheumatic heart disease in the population being reported. Rheumatic fever and, thus, rheumatic MS, disproportionately affects developing countries and the low-income groups in developed countries that lack access to health care and treatment for Streptococcus pyogenes infections. Although rheumatic heart disease is the primary cause of MS—largely driven by its prevalence in the developing world (ranging from 46 to 2400 cases per 100,000)—the incidence is dropping, and nonrheumatic MV calcification is an increasingly common cause of MS and/or MR.6 This increase in nonrheumatic mitral calcinosis is most probably related to the older average age of patients, increased frequency of multiple cardiovascular risk factors, and increased prevalence of chronic kidney disease.7 Other modern disease entities, such as metabolic and autoimmune disorders, also contribute to nonrheumatic MS.7,8
PATHOGENESIS
Mitral Regurgitation
MR occurs, chiefly, when there is malcoaptation of the leaflets, allowing for regurgitant flow from the LV to the LA. It has been categorized in several ways, but most useful is the distinction between degenerative and functional MR.
Degenerative Mitral Regurgitation
Degenerative MR (aka primary MR) is due to inherent or acquired pathology of the valve leaflets, chordae tendinae, or papillary muscles. Degenerative MR may be secondary to MV prolapse or myxomatous MV disease, which sometimes progresses to chordae tendinae rupture, as a result of leaflet malcoaptation. Rheumatic heart can also lead to valve leaflet and chordal thickening that decreases leaflet pliability and prevents adequate leaflet coaptation. Valve leaflet degeneration can also be observed with MV endocarditis. In recent decades, infectious endocarditis has become predominantly associated with Staphylococcus aureus and coagulase-negative Staphylococcus bacteremia as a result of intravenous drug use and health care-associated infections, respectively.6 Valve calcinosis is increasingly recognized as a source of degenerative valve disease, whereby calcium deposits collect along the annulus, chordae, and valve leaflets, leading to restriction in leaflet movement, poor coaptation, and regurgitation.7 Iatrogenic causes of leaflet destruction include radiation-induced and medication-induced (eg, serotonergic appetite suppressants such as fenfluramine or benfluorex and ergot-derived dopamine agonists such as cabergoline or
pergolide, etc) valve disease result in calcified and noncalcified fibrous plaques, respectively, and resultant restrictive valvulopathy.9,10,11 Serotonin-receptor-related MV pathology has a characteristic short, stubby appearance of the mitral leaflets, which is pathognomonic.
pergolide, etc) valve disease result in calcified and noncalcified fibrous plaques, respectively, and resultant restrictive valvulopathy.9,10,11 Serotonin-receptor-related MV pathology has a characteristic short, stubby appearance of the mitral leaflets, which is pathognomonic.
 FIGURE 10.1 Highlighted anatomy of the mitral valve. |
Regardless of the mechanism of chronic degenerative MR, regurgitant flow into the LA increases LA pressure, which elevates pulmonary venous pressure and, if severe, causes pulmonary edema. Over time, the LA dilates to accommodate the regurgitant volume and decrease LA pressure. The increased LV end-diastolic volume (as a result of retrograde plus antegrade blood flow) precipitates eccentric hypertrophy of the LV to accommodate the larger stroke volumes and preserve antegrade flow (compensated chronic MR).12 Over time, this LV volume overload results in contractile myofibril loss, reduced LV contractility, and chronic heart failure.13 Avoiding or halting this natural history is the goal of treatment interventions.
Functional Mitral Regurgitation
Functional MR (eg, secondary MR) is related to disruptions of the supporting valve apparatus despite the presence of normal leaflet and chordae tissue. The most common cause of functional MR is a dilated LV (seen in both nonischemic cardiomyopathy and late compensatory manifestations of ischemic cardiomyopathies) with stretching of the mitral annulus.4,6 Thus, functional MR can be viewed as a pathologic consequence of heart failure rather than the initial precipitant of heart failure, although they may be coincident or intertwined. Ischemic heart disease that causes focal infarcts of the LV papillary muscles can also lead to functional MR resulting from restriction of this subvalvular mitral component. Papillary muscle dysfunction can occur acutely with myocardial ischemia, leading to acute MR, or as a component of chronic ischemic heart disease and result in chronic MR. Dilated cardiomyopathy of the LA is similarly thought to cause functional MR, although isolated dilated atrial cardiomyopathy is much
less common and typically occurs in concert with other left heart structural pathology.1
less common and typically occurs in concert with other left heart structural pathology.1
Mitral Stenosis
MS is rarely congenital; but when it occurs, it may be supravalvular, subvalvular, or due to leaflet narrowing in association with other left heart congenital lesions.
Most commonly, MS is due to rheumatic fever, with the reduced orifice area caused by restricted leaflet excursion. Rheumatic carditis manifests with characteristic inflammatory Aschoff nodules and thickening of the valvular and subvalvular components, which subsequently leads to reduced leaflet mobility and fusion of leaflet commissures.14
Severe mitral annular calcification (MAC) or subvalvular calcification can also reduce the orifice area of the MV apparatus. Bulky calcific buildup along the circumference of the valve annulus can lead to concentric narrowing of the valve area, whereas calcific deposits of the valve structures can restrict leaflet mobility and excursion, which further reduces the mitral orifice.7
CLINICAL PRESENTATION
Common Signs and Symptoms
Mitral Regurgitation
Owing to the pathophysiologic changes described earlier, chronic MR results in LA and LV dilatation, pulmonary venous hypertension, heart failure, and arrhythmias. Patients commonly complain of typical heart failure symptoms: fatigue, dyspnea on exertion, orthopnea, chest discomfort, shortness of breath, and peripheral edema. Arrhythmias can provoke palpitations.
The characteristic blowing, holosystolic murmur is best heard at the LV apex (which may be displaced to the axilla), and may radiate to the axilla or left infrascapular area overlying the LA. Radiation of the murmur to the parasternal region can occur if valve pathology creates an anteriorly directed regurgitant jet. The murmur increases in intensity with maneuvers that increase afterload (eg, handgrip or arterial compression with blood pressure cuff) or preload (such as squatting). Murmur intensity does not correspond well to MR severity. The timing of the murmur in systole can vary depending on the MV pathology; with MV prolapse, the murmur is mid-late systolic, whereas an early systolic murmur is observed with functional MR. The mitral component of S1 is soft or absent. An S3 and low-pitch, soft diastolic flow murmur can be present from LA volume overload. Other physical examination findings consistent with heart failure may be present, including rales, jugular venous distension, pitting-dependent edema, and laterally displaced cardiac point of maximal impulse. A parasternal heave may be palpated if pulmonary hypertension is present. As with more advanced heart failure, ascites, hepatosplenomegaly, or cardiac wasting can occur.
Acute MR manifests as pulmonary edema and acute decompensation, and is usually due to valve destruction from endocarditis, ruptured or flail chordae from myxomatous MV prolapse, or papillary muscle dysfunction with active ischemia, or papillary muscle rupture following acute myocardial infarction. Acute MR generates a soft, short, early, systolic murmur as the systolic pressures in the noncompliant LA and LV equalize rapidly, halting regurgitant flow early and making auscultatory diagnosis difficult. Isolated right middle or upper lobe rales and lobar consolidation can be present when the regurgitant jet is directed at the right upper pulmonary vein with acute MR, although bilateral pulmonary edema is more common.15
Mitral Stenosis
Owing to the insidious progression of symptoms, patients often do not appreciate their slow decline in functional capacity. Patients may experience symptoms of dyspnea, orthopnea, pulmonary edema, and hemoptysis. With less blood flow across the stenotic valve, the LV is often small and underfilled, and can manifest as symptoms of hypotension or dizziness with exertion or standing up. Atrial arrhythmias, such as atrial fibrillation, from the dilated LA are common and are noted as palpitations or tachycardia. Lastly, thromboembolic phenomenon, including stroke or embolism to the coronary arteries or visceral organs, can be the sentinel event.
In developed countries, MS usually manifests two to three decades after an episode of acute rheumatic fever; hence, pregnancies are generally unaffected. However, in developing countries where rheumatic fever is endemic, individuals may experience multiple episodes of rheumatic fever, which accelerates the development of MS. In this situation, MS can be seen in the second and third decades of life, and often complicates pregnancy with resultant miscarriages, pulmonary edema, or death.
Auscultation for MS is best performed with the patient in the left lateral decubitus position to reveal the “opening snap” of the mitral leaflets, followed by a soft diastolic rumbling murmur and prominent S1 in the apical region. Irregular rhythms are common. Patients with pulmonary hypertension can have a prominent pulmonic component of the second heart sound, a right ventricular heave, and signs of right heart failure such as peripheral edema, hepatosplenomegaly, and ascites frequently in the absence of rales (unless acute decompensation).
Chest radiographs can show prominent pulmonary vasculature and LA enlargement, but pulmonary edema is less common because the pulmonary vessels have remodeled and are “protected” from any elevations in LA pressure unless in the setting of acute hemodynamic decompensation such as paroxysmal rapid atrial fibrillation. Electrocardiogram can reveal LA enlargement and atrial arrhythmias with an absence of LV hypertrophy.
Differential Diagnosis
When considering the differential diagnoses for etiologies of MV disease, special consideration should be paid to the acuity of symptom onset and a focused history of risk factors.
Mitral Regurgitation
Acute MR is most often from sudden rupture of a myxomatous chordae or leaflet segment, acute ischemia of the papillary muscle from coronary artery disease, postinfarction rupture of a papillary muscle, direct trauma, or bacterial endocarditis. Chronic primary MR is associated with myxomatous valve disease or MV prolapse, calcific degeneration, remote rheumatic fever, infectious or autoimmune endocarditis, papillary muscle
dysfunction due to nonischemic cardiomyopathy, or prior inferolateral myocardial infarction. Secondary MR is usually due to LV dilation from any cause, mostly from ischemic or nonischemic cardiomyopathy
dysfunction due to nonischemic cardiomyopathy, or prior inferolateral myocardial infarction. Secondary MR is usually due to LV dilation from any cause, mostly from ischemic or nonischemic cardiomyopathy
Mitral Stenosis
MS is predominantly from rheumatic MV disease. Rarely, it could be from lupus or autoimmune inflammation. In the elderly, calcific MV stenosis may be associated with MAC or hemodialysis-dependent end-stage renal disease. Congenital MS or parachute MV causing stenosis is rare. Similar presentations are rarely seen with flow-obstructing cardiac thrombus or cardiac tumor (ie, LA myxoma).
A careful history of rheumatic fever in childhood should be sought from family members who may remember the episode. Prolonged absence from school, frequent sore throats, tonsillectomy/adenoidectomy, multiple family members living in a small cloistered home, family members with frequent sore throats, and history of painful monthly penicillin injections are helpful clues to prior rheumatic fever.
DIAGNOSIS: MITRAL VALVE DISEASE
The diagnosis of MV disease and assessment of severity is now largely based on noninvasive imaging results. Echocardiography, magnetic resonance imaging (MRI), and computed tomography (CT) are used in the assessment of MV disease (see Table 10.1). Notably, the imaging criteria for diagnosis should incorporate multiple supportive findings to assess disease severity, not just one, because each measurement has its pitfalls for inaccuracy. For example, the diagnosis of MR should not rely on color Doppler findings alone, and the diagnosis of MS should not be based on planimetry or pressure half-time measurements alone. This approach of multiple complementary measurements is recommended. But, ultimately, clinical judgment utilizing history of present illness, imaging, and physical examination, is critical for providing optimal patient care.
Echocardiography
Echocardiographic imaging is the gold standard for diagnosis of MV disease, because it provides measurements of blood flow, pressure gradients, and anatomic visualization when used properly. It is most commonly performed via transthoracic views. Alternatively, a transesophageal echocardiogram (whereby the probe is advanced into the esophagus) provides an added advantage of imaging in close proximity to the MV given the anatomic approximation of the esophagus to the LA. The improved visualization of the MV with transesophageal echocardiogram is further enhanced by three-dimensional imaging. Exercise echocardiography is recommended when imaging at rest does not adequately assess the significance of a valvular lesion. Imaging with exercise demonstrates the hemodynamic consequences of MR and MS during exertion with elevated heart rate (shortened diastole) and increased flow, when the most symptoms are present.
Diagnostic criteria for MR and MS include qualitative, semiquantitative, and quantitative assessments summarized in Tables 10.2 and 10.3 adapted from the American Society for Echocardiography and European Association of Echocardiography. The severity of MV disease is predominantly characterized by semiquantitative and quantitative flow measurements, whereas visualization of the MV apparatus and supporting structures is most critical to differentiating between degenerative or functional MR as well as mechanisms of MS. Coexisting pathology and differing hemodynamic states can impact the accuracy of each of these measurements and their assessment of severity of valve disease.16 For example, reduced blood flow or LV diastolic dysfunction can affect transvalvular gradient assessments and accurate diagnosis. A commonly encountered scenario occurs when patients have severe MR on transthoracic echocardiogram while conscious and then undergo transesophageal echocardiogram for further study, wherein anesthesia decreases cardiac preload and systemic vascular afterload, and the MR severity is less than it is when awake. Another opportunity for underdiagnosis is seen with acute MR at a time where there has not been the progressive increase in pulmonary vascular resistance (seen with chronic MR), and there is unimpeded regurgitant flow such that the pressure gradient between the LV and LA equalizes so rapidly that Doppler and color-flow Doppler assessments appear very brief, thereby making it difficult to appreciate the hemodynamic severity. Owing to the interplay of various patient and technologic limitations, accurate diagnosis requires an experienced echocardiogram interpreter to reconcile multiple diagnostic criteria and comorbidities.
Certain echocardiographic findings are unique to specific mitral disease etiologies. Rheumatic MS classically includes a hockey stick shape to the anterior leaflet when viewed in the parasternal long axis during diastole.17 This shape is due to the thickening of the leaflet and commissural fusion that creates a less mobile hinge point in the midpoint of the leaflet, creating this characteristic appearance. Ergotamine-induced valve disease, metastatic carcinoid heart disease, and fenfluramine-phentermine-associated heart disease share a common pathway of serotonin-mediated endocardial fibrosis. This creates the classic appearance of short, thick-valve leaflets with regurgitation. Although these three syndromes may not be fully distinguishable by echocardiogram alone, a focused history will establish the diagnosis.
Magnetic Resonance Imaging
Cardiac MRI is a useful additional method for evaluation of mitral disease, particularly for assessment of the severity of MR and mechanism of LV remodeling, myocardial viability, and myocardial scarring.16 The benefits of MRI include evaluation of the entire heart without limitations in imaging windows or body habitus that occur with echocardiography. Accordingly, cardiac MRI may be more accurate than is echocardiography in quantifying the severity of MR.17
LV and right ventricular function, valve structure, and apparatus can be thoroughly evaluated. Regurgitation severity can be assessed via planimetry or, more accurately, via regurgitant volume using either the direct measurement of velocity-encoded sequences of the regurgitant jet or indirectly with easily obtained three-dimensional cardiac volume
measurement.18 The regurgitant volume is calculated from measurements of LV stroke volume—derived from measurements of the LV end-diastolic and end-systolic volumes—crossing the aortic valve and comparison with LA volumes. The difference of LV stroke volume and stroke volume across the aortic valve is computed as the mitral regurgitant volume.16
measurement.18 The regurgitant volume is calculated from measurements of LV stroke volume—derived from measurements of the LV end-diastolic and end-systolic volumes—crossing the aortic valve and comparison with LA volumes. The difference of LV stroke volume and stroke volume across the aortic valve is computed as the mitral regurgitant volume.16
TABLE 10.1 Recommended Diagnostic Imaging of Mitral Valve Disease | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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The use of MRI in the evaluation of MS is directed at a thorough evaluation of the MV apparatus and degree of leaflet restriction and mobility. Calcium deposition within the leaflets and annulus can be appreciated, but this is best evaluated and characterized with CT. The degree of stenosis and calculation of valve area can be quantified via two methods using MRI: planimetry and pressure half-time. Pressure half-time has been shown to overestimate valve area when compared to echocardiography, whereas planimetry has a result more comparable to that of echocardiography, and thus is considered a more reliable means of evaluation.18
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