Mitral valve disorders are among the most common valvular diseases with an increasing prevalence in the aging population. It is estimated that over 10% of patients over 75 years old have significant mitral valve disease with most of these due to mitral regurgitation (MR). The decreasing incidence of rheumatic heart disease has made mitral stenosis increasingly rare in the United States, although it remains a problem in developing nations and is a significant global health issue.
The hemodynamic abnormalities associated with mitral stenosis and regurgitation lead to interesting and complex challenges for physicians. Major decisions regarding the treatment of mitral valve disease are often based on these evaluations, and it is important for the physician to appreciate the limitations and potential sources of error when evaluating these conditions. Furthermore, understanding mitral valve hemodynamics is crucial as new transcatheter therapies are developed and applied to these conditions.
Mitral Stenosis
Rheumatic heart disease is the most common cause of mitral stenosis; other etiologies are rare ( Box 5.1 ). Mitral annular calcification is becoming increasingly prevalent in our aging population; however, it rarely causes severe stenosis. Although rheumatic heart disease has decreased dramatically in the United States, it continues to affect populations with substandard medical care, including Mexican Americans, Native Americans, and immigrants from developing nations. Pathologically rheumatic mitral stenosis results from several mechanisms, including commissural fusion, cuspal fibrosis and thickening, and chordal fusion and thickening ( Fig. 5.1 ). Other nonrheumatic pathologic conditions causing mitral stenosis are very rare.
- 1.
Rheumatic heart disease
- 2.
Mitral annular calcification
- 3.
Congenital mitral stenosis
- 4.
Lupus
- 5.
Infective endocarditis/vegetation
- 6.
Carcinoid
- 7.
Rheumatoid arthritis
- 8.
Methysergide therapy
- 9.
Radiation-induced valve disease
- 10.
Prosthetic mitral valve dysfunction
The unobstructed, normal mitral valve orifice area measures approximately 4 cm 2 . Symptoms become apparent when the valve area falls below 2 cm 2 , and stenosis is classified as “severe” when the valve area measures <1.5 cm 2 . The natural history of mitral stenosis is characterized by a long latent period lasting many years, with patients experiencing either no or minimal symptoms. Symptoms may arise insidiously over many years and lead to progressive disability from dyspnea or fatigue. Alternatively, a patient may experience the abrupt onset of symptoms from either the development of rapid atrial fibrillation (AF) or acute volume overload. Important complications that arise from the natural history of mitral stenosis include AF, cerebral and peripheral embolic events, hemoptysis, pulmonary hemorrhage, pulmonary hypertension and right-sided heart failure, endocarditis, and increased predisposition to infections.
Pathophysiology of Mitral Stenosis
Obstruction of the mitral valve causes a pressure gradient between the left atrium and left ventricle. The presence of this pressure gradient throughout diastole defines the hemodynamic hallmark of significant mitral valve stenosis. Very mild degrees of mitral stenosis have either an undetectable or very small diastolic gradient. With the progressive narrowing of the mitral valve, left-atrial pressure rises and the gradient becomes more pronounced. In addition to elevating left-atrial pressure, incomplete emptying of the left atrium impairs filling of the left ventricle and diminishes cardiac output.
Because the left atrium is in series with the pulmonary circulation, elevated left-atrial pressure passively elevates pressure in the pulmonary veins and arteries. Early in the course of the disease, pulmonary vascular resistance is normal with little effect on the right heart. As the condition progresses and becomes more chronic, the pulmonary artery pressures rise further. Pulmonary hypertension is initially due to reactive changes in the pulmonary arteriolar bed and is reversible. Marked pulmonary hypertension may result and reach systemic levels, obstructing blood flow through the lungs (the “second” stenosis of mitral stenosis), further decreasing cardiac output. Pulmonary vascular resistance increases substantially, causing enlargement of the right ventricle and right-sided heart failure. Although pulmonary hypertension is usually reversible following relief of mitral stenosis by either surgery or balloon valvotomy, with advanced, end-stage mitral stenosis, pulmonary hypertension may become fixed from permanent anatomic changes in the pulmonary arteries and arterioles.
The left-atrial pressure and the cardiac output are the main determinants of symptoms in patients with mitral stenosis. Elevated left-atrial pressure causes dyspnea, pulmonary edema, and hemoptysis. The low cardiac output associated with this condition causes fatigue. In addition to the mitral valve orifice area, left-atrial pressure depends on the rate of flow across the valve (i.e., cardiac output), heart rate, size and compliance of the left atrium, and volume status; heart rate and volume status are particularly important. If given enough time, the left atrium will eventually empty even in the presence of severe mitral stenosis. Thus for any given mitral valve area, bradycardia will result in lower left-atrial pressures, and tachycardia will result in higher left-atrial pressures. For this reason, the onset of rapid AF is poorly tolerated and leads to the abrupt onset of symptoms including acute pulmonary edema. Similarly acute volume overload will rapidly increase left-atrial pressure, leading to dyspnea or pulmonary edema.
Hemodynamics of Mitral Stenosis
A wide spectrum of hemodynamic abnormalities is possible in patients with mitral stenosis, depending on the stage of their disease. Initially the major hemodynamic abnormalities reflect solely the mitral valve obstruction and include (1) elevation of the left-atrial or wedge pressure, typically to 20–25 mm Hg, with normal or low left-ventricular end-diastolic pressure (LVEDP); (2) the presence of a pressure gradient that exists throughout diastole between the left atrium and left ventricle, usually ranging from 5 to 25 mm Hg; (3) a reduction in cardiac output (3.5–4.5 L/min); and (4) abnormalities in the left-atrial pressure tracing, affecting both a and v waves. In patients with normal sinus rhythm and mitral stenosis the a wave on the left-atrial or pulmonary capillary wedge pressure (PCWP) waveform may be accentuated because of the increased residual volume of the atrium at the onset of atrial systole ( Fig. 5.2 ). The a wave may be quite large, and values as high as 50 mm Hg have been described. A prominent v wave may also be observed in pure mitral stenosis because left-atrial volume and pressure are already high, and any additional increase in volume that occurs during passive atrial filling results in a greater increase in pressure, generating prominent v waves ( Fig. 5.3 ). There also may be a contribution to reduced left-atrial compliance from fibrosis. The presence of a large v wave correlates strongly with diminished exercise tolerance and is a significant predictor of pulmonary hypertension. Furthermore, because mitral stenosis delays emptying of the left atrium, the slope of the y descent, representing the phase of early and rapid ventricular filling, is delayed ( Fig. 5.4 ) compared with the rapid descent seen in MR.
In the early stages of the disease pulmonary pressures are normal and then become modestly elevated, despite the presence of severe mitral orifice narrowing. At this stage the high pulmonary artery pressures reflect elevated left-atrial pressure; the pulmonary vascular resistance is normal. Over time, however, the pulmonary vascular resistance increases due to reactive changes, and right-ventricular enlargement occurs. Late stages of mitral stenosis are associated with marked pulmonary hypertension due to permanent anatomic changes in the arterioles, causing extreme elevations in pulmonary vascular resistance, pronounced right-ventricular failure, and severe secondary tricuspid regurgitation.
The existence of a pressure gradient between the left atrium and left ventricle during diastole both defines mitral stenosis and forms the basis of the hydraulic formula derived to calculate the mitral valve orifice area. In patients without mitral stenosis, left-atrial and left-ventricular diastolic pressure curves appear nearly superimposable ( Fig. 5.5A ). In fact a very small gradient must normally exist to allow blood to flow from the left atrium into the left ventricle ( Fig. 5.5B ), but this is often not appreciable by the clinically used, fluid-filled transducers. In contrast, in mitral stenosis, a pressure gradient is present immediately on opening of the mitral valve and persists in diastole so that diastasis is absent ( Figs. 5.2–5.4 ).
The transmitral gradient is ideally assessed by obtaining simultaneous pressure waveforms from catheters positioned in the left atrium and left ventricle. However, most physicians are not facile at the performance of transseptal catheterization, and the PCWP is typically substituted for left-atrial pressure. Although this practice may be acceptable in some cases, the potential for considerable error exists, and the limitations of this technique must be understood. Thus when an important decision hinges on an accurate measurement of the pressure gradient across the mitral valve, transseptal catheterization is necessary.
In general, the PCWP correlates well with left-atrial pressure. This is particularly true when the PCWP is low (<25 mm Hg), with no significant difference noted between left-atrial pressure and the PCWP. When the PCWP is >25 mm Hg, considerable error may exist (variance in excess of 10 mm Hg).
Although a good correlation exists between the mean left-atrial pressure and mean PCWP, the transmitral gradient using the PCWP does not correlate as well with the gradient obtained using the left-atrial pressure. Major sources of error exist; first, the PCWP introduces a considerable time delay (40–160 ms depending on the position of the catheter), and this pushes the v wave into diastole; and second, intrinsic to the generation of a wedge pressure, there is dampening of the PCWP waveform. In general, these factors lead to an overestimation of the pressure gradient ( Fig. 5.6 ). In addition, in the presence of pulmonary hypertension (a common occurrence in patients with mitral stenosis), it may not be possible to obtain a true PCWP from the pulmonary artery position, and instead the waveform represents a hybrid between the true wedge pressure and the pulmonary artery pressure, and this falsely elevates the “wedge.” These factors conspire to elevate the mean diastolic gradient compared with that obtained with left-atrial pressure. Adjustment for the time delay by phase shifting the tracing relative to the left-ventricular pressure provides a more accurate reflection of the left-atrial–left-ventricular pressure gradient. However, several experts believe that these inaccuracies make the use of the PCWP an unreliable gauge of the transmitral gradient, and thus this method should not be used to make major decisions such as referral for mitral balloon valvuloplasty or mitral valve surgery. Importantly, if the PCWP is used, the operator must pay meticulous attention to detail and confirm the wedge pressure using oximetry sampling to demonstrate an arterial saturation >95%. In our practice, the use of simultaneous PCWP-left ventricular waveforms is useful to exclude the presence of a mitral gradient. However, in patients with evidence of a significant gradient using the PCWP who have discrepant noninvasive studies, poor-quality wedge pressure waveforms, pulmonary hypertension, or prior prosthetic valve surgery, transseptal catheterization should be performed to confirm the gradient with a left-atrial pressure measurement before making a major decision related to the mitral valve stenosis.
A transmitral gradient has several causes other than true mitral stenosis ( Box 5.2 ). Severe mitral annular calcification may result in a transmitral gradient. This may be seen in association with calcific aortic stenosis ( Fig. 5.7 ) or in patients with renal failure. Typically the gradient is modest (averaging 4 mm Hg by echocardiography). Although there is little published data, in our experience, echocardiography tends to overestimate the pressure gradient in the presence of severe mitral annular calcification. This is likely because these estimates are based on Doppler velocities and these may be increased because of annular restriction and compliance issues rather than true stenosis. In many cases, when invasive assessment is performed with transseptal catheterization, the transmitral gradient is found to be significantly less than the value measured by echocardiography ( Fig. 5.8 ). The hemodynamics of mitral annular calcification is described in more detail later in this chapter.
- 1.
Mitral valve stenosis
- 2.
Mitral annular calcification
- 3.
Severe mitral regurgitation
- 4.
Atrial myxoma (rare)
- 5.
Cor triatriatum or pulmonary venoocclusive disease (very rare)
- 6.
Hemodynamic artifacts
Improper zeroing, transducer balancing, or calibration
Pulmonary artery catheter not in true “wedge” position
Large v waves on pulmonary capillary wedge pressure
A pressure gradient may be present in patients with severe MR (averaging about 6 mm Hg) because of the marked increase in flow across the valve, but it is observed only in early diastole.
More important are several artifactual conditions resulting in an apparent transmitral gradient. Meticulous attention to detail is important when making these measurements, and pressure transducers should first be carefully leveled, calibrated, and zeroed. Because the pressures under consideration are relatively low, small errors in zeroing, improper catheter flushing, transducer level, or differences in frequency response between the two transducers may cause the false appearance of a transmitral gradient. Probably the most common artifact is due to the inability of the operator to achieve a true “wedge” position, particularly when severe pulmonary hypertension is present. In this scenario the pressure wave represents a hybrid between the true wedge pressure and the pulmonary artery systolic pressure, falsely causing or elevating the gradient ( Fig. 5.9 ). Because of the time delay inherent to the generation of the PCWP waveform, a large v wave will appear within diastole and give the impression that there is an elevated gradient ( Fig. 5.10 ). A transseptal catheterization with direct measurement of left-atrial pressure will demonstrate the absence of stenosis ( Fig. 5.11 ).
Calculation of Mitral Valve Area Using the Gorlin Formula
Richard Gorlin and his father derived the Gorlin equation in 1951 based on the physics of hydraulic systems. First, Gorlin chose the hydraulic formula for determining the area of a “rounded edge” orifice:
where F = flow, A = orifice area, and V = the change in velocity of flow across the orifice. The value Cc represents the coefficient of orifice contraction to allow for the contraction of the stream as it passes through the orifice. This formula is then combined with the relationship:
where g = the gravitational constant (980 cm/s 2 ) and h = the height of the column of fluid and can be substituted for the pressure gradient across the orifice. The value Cv represents the coefficient of velocity to account for the loss of energy through friction and turbulence. The two formulas are then combined and simplified and a single empiric constant “C” is created to account for the various coefficients to produce the essence of the Gorlin formula, which states:
Mitral valve flow is defined as the flow that occurs during diastole (diastolic filling period). Gorlin determined the empiric constant as 0.7 by collecting the hemodynamics from a single patient with mitral stenosis, measuring the actual valve area by autopsy after the patient died, and solving the formula for C. Because Gorlin had no method to measure LVEDP, he assumed a value of 5 mm Hg and determined the diastolic filling period from the brachial artery tracing as the beginning of the dicrotic notch to the beginning of the upstroke of the next pressure pulse. Validation consisted of measurements obtained in 11 patients (6 autopsy and 5 surgical cases) with good correlation. Once LVEDP could be measured routinely, the Gorlin constant was corrected from 0.7 to 0.85, and the Gorlin formula evolved into its present form :
The pressure gradient represents the mean gradient and, in the current era, is typically measured with automated, computer-based hemodynamic systems. In normal sinus rhythm, five cardiac cycles are averaged. Because of the marked variation in the gradient with varying RR intervals, at least 10 cardiac cycles are required for patients with AF ( Fig. 5.12A ). Note the effect on the gradient following the compensatory pause after a premature ventricular contraction, as shown in Fig. 5.12B . The longer duration of diastole allows more time for the atrium to empty and reduces the end-diastolic gradient. As noted earlier, if the patient is in sinus rhythm and the PCWP is used instead of left-atrial pressure, the presence of a large v wave can falsely add to the gradient.
A much-simplified version of the Gorlin formula for calculating valve area has been proposed. The formula is easy to remember and eliminates the heart rate, diastolic filling period, and empiric constant:
When compared to the traditional Gorlin formula, the simplified formula may lead to significant disparity, especially if tachycardia is present (heart rate > 100 beats/min). Therefore the simplified formula should be used with great caution.
The Gorlin formula for valve area calculation has several well-known criticisms and limitations. The formula is based on idealized relationships between flow across valves and orifice area and makes many assumptions and oversimplifications to create a tidy mathematical formula. The formula works best if normal sinus rhythm is present and is within the normal physiologic range of flows. Coexisting MR represents a significant limitation of this method as the Gorlin formula underestimates the true valve area because the cardiac output entered in the numerator is the forward flow and does not account for the regurgitant fraction included in the total transmitral diastolic flow.
In the event that a hemodynamic evaluation reveals only mild to moderate stenosis but a more severe valve lesion is suspected clinically, hemodynamics can be done under exercise conditions in the cardiac catheterization laboratory. While sometimes awkward to perform, even just a few minutes of upper arm exercise can cause increased heart rate and cardiac output and may allow a more clear assessment of the severity of stenosis. This discrepant scenario can be evaluated further noninvasively by assessing the gradients across the mitral valve and pulmonary pressures utilizing an echocardiographic stress test (preferably physical exercise or alternatively using dobutamine). This is also useful when evaluating females with mitral stenosis in the moderate to severe range and who are asymptomatic, particularly for individuals who are contemplating pregnancy, as pregnancy generally leads to an increase in cardiac output, heart rate, transmitral flow, and total blood volume, each of which can worsen transvalvular mitral gradients.
The severity of mitral valve stenosis is routinely evaluated noninvasively. Echocardiographic techniques include the use of two-dimensional (2D) echocardiography with planimetry of the mitral valve area and the use of Doppler echocardiographic techniques, including the pressure half-time and continuity equation methods. Although these techniques correlate reasonably well with the invasively determined techniques that rely on the Gorlin formula, considerable variability may exist between the methods in patients with symptomatic and significant mitral stenosis. This is particularly true in patients with lower transmitral gradients and higher cardiac outputs. Importantly clinicians should not fixate on the absolute value generated by these studies or rely solely on a single determination of the severity of stenosis. One series found that 12% of patients who underwent mitral valve surgery with severe symptoms and mitral stenosis had relatively small gradients (<10 mm Hg) and only modest narrowing by calculated valve area (1.6 cm 2 ) yet improved dramatically with surgery, emphasizing the point that nothing substitutes for clinical judgment.
There are several echocardiographic findings characteristic of rheumatic mitral stenosis. First, there is commissural fusion with valvular thickening, particularly at the free edge of the leaflets. This is usually best seen in the parasternal short-axis view. Later thickening extends toward the base with further restriction of valve motion. Second, there is reduced leaflet mobility and restricted opening. The posterior leaflet is usually partially or completely immobile and the anterior leaflet shows a diastolic doming, producing the characteristic “hockey stick” configuration. This is usually best seen in the parasternal long-axis view. Third, there is involvement of the subvalvular apparatus with thickened, fused, and/or shortened chords. Finally, calcification is usually apparent of the leaflets and the subvalvular apparatus with more calcification seen in older patients with long-standing disease.
Direct planimetry of the mitral valve area is one method to evaluate mitral stenosis severity. 2D planimetry is performed in the parasternal short-axis view. It involves tracing the inner edge of the mitral valve orifice in mid-diastole. This measurement is made at the leaflet tips, ensuring the narrowest valve orifice. To select an adequate alignment of the valve orifice plane, a careful scanning from base to apex should be performed ( Fig. 5.13 ). Zoomed images should be acquired, and an excessive gain setting should be avoided as it may lead to underestimation of the mitral valve area. 2D planimetry is a direct anatomic measurement. It is independent of load conditions, chamber stiffness, and concomitant valve disease and reliably correlates with the size of the anatomic orifice. Potential errors in this measurement include a more atrial level of tracing and thus missing the narrowest point of the valve, inadequate acoustic windows, and severe calcification or distortion of the leaflets. Among these limitations, inadequate alignment of the image plane is the main source of error. Due to these limitations, the severity of mitral stenosis should not be defined solely by this parameter, and an integrated approach is recommended. Three-dimensional echocardiography (3DE) is superior in evaluating mitral stenosis severity because the direct visualization of the valve orifice in multiple planes ensures that the planimetry takes place at the level of the mitral leaflet tips, where the valve orifice is narrowest. Limitations of 3DE include reduced spatial and temporal resolution compared to 2D echocardiography and suboptimal images in patients with arrhythmias.
