Rheumatic fever is the leading cause of mitral stenosis (MS) (Table 284-1). Other less common etiologies of obstruction to left ventricular inflow include congenital mitral valve stenosis, cor triatriatum, mitral annular calcification with extension onto the leaflets, systemic lupus erythematosus, rheumatoid arthritis, left atrial myxoma, and infective endocarditis with large vegetations. Pure or predominant MS occurs in approximately 40% of all patients with rheumatic heart disease and a history of rheumatic fever (Chap. 381). In other patients with rheumatic heart disease, lesser degrees of MS may accompany mitral regurgitation (MR) and aortic valve disease. With reductions in the incidence of acute rheumatic fever, particularly in temperate climates and developed countries, the incidence of MS has declined considerably over the past several decades. However, it remains a major problem in developing nations, especially in tropical and semitropical climates.
TABLE 284-1Major Causes of Mitral Valve Disease ||Download (.pdf) TABLE 284-1Major Causes of Mitral Valve Disease
|Valve Lesion ||Etiologies |
|Mitral stenosis ||Rheumatic fever |
| ||Congenital |
| ||Severe mitral annular calcification |
| ||SLE, RA |
|Mitral regurgitation ||Acute |
| || Endocarditis |
| || Papillary muscle rupture (post-MI) |
| || Trauma |
| || Chordal rupture/leaflet flail (MVP, IE) |
| ||Chronic |
| || Myxomatous (MVP) |
| || Rheumatic fever |
| || Endocarditis (healed) |
| || Mitral annular calcification |
| || Congenital (cleft, AV canal) |
| || HOCM with SAM |
| || Ischemic (LV remodeling) |
| || Dilated cardiomyopathy |
| || Radiation |
In rheumatic MS, chronic inflammation leads to diffuse thickening of the valve leaflets with formation of fibrous tissue and/or calcific deposits. The mitral commissures fuse, the chordae tendineae fuse and shorten, the valvular cusps become rigid, and these changes, in turn, lead to narrowing at the apex of the funnel-shaped (“fish-mouth”) valve. Although the initial insult to the mitral valve is rheumatic, later changes may be exacerbated by a nonspecific process resulting from trauma to the valve due to altered flow patterns. Calcification of the stenotic mitral valve immobilizes the leaflets and narrows the orifice further. Thrombus formation and arterial embolization may arise from the calcific valve itself, but in patients with atrial fibrillation (AF), thrombi arise more frequently from the dilated left atrium (LA), particularly from within the LA appendage.
In normal adults, the area of the mitral valve orifice is 4–6 cm2. In the presence of significant obstruction, i.e., when the orifice area is reduced to < ~2 cm2, blood can flow from the LA to the left ventricle (LV) only if propelled by an abnormally elevated left atrioventricular pressure gradient, the hemodynamic hallmark of MS. When the mitral valve opening is reduced to <1.5 cm2, referred to as “severe” MS, an LA pressure of ~25 mmHg is required to maintain a normal cardiac output (CO). The elevated pulmonary venous and pulmonary arterial (PA) wedge pressures reduce pulmonary compliance, contributing to exertional dyspnea. The first bouts of dyspnea are usually precipitated by clinical events that increase the rate of blood flow across the mitral orifice, resulting in further elevation of the LA pressure (see below).
To assess the severity of obstruction hemodynamically, both the transvalvular pressure gradient and the flow rate must be measured (Chap. 272). The latter depends not only on the CO but on the heart rate, as well. An increase in heart rate shortens diastole proportionately more than systole and diminishes the time available for flow across the mitral valve. Therefore, at any given level of CO, tachycardia, including that associated with rapid AF, augments the transvalvular pressure gradient and elevates further the LA pressure. Similar considerations apply to the pathophysiology of tricuspid stenosis.
The LV diastolic pressure and ejection fraction (EF) are normal in isolated MS. In MS and sinus rhythm, the elevated LA and PA wedge pressures exhibit a prominent atrial contraction pattern (a wave) and a gradual pressure decline after the v wave and mitral valve opening (y descent). In severe MS and whenever pulmonary vascular resistance is significantly increased, the PA pressure (PAP) is elevated at rest and rises further during exercise, often causing secondary elevations of right ventricular (RV) end-diastolic pressure and volume.
In patients with severe MS (mitral valve orifice 1–1.5 cm2), the CO is normal or almost so at rest, but rises subnormally during exertion. In patients with very severe MS (valve area <1 cm2), particularly those in whom pulmonary vascular resistance is markedly elevated, the CO is subnormal at rest and may fail to rise or may even decline during activity.
The clinical and hemodynamic features of MS are influenced importantly by the level of the PAP. Pulmonary hypertension results from: (1) passive backward transmission of the elevated LA pressure; (2) pulmonary arteriolar constriction (the so-called “second stenosis”), which presumably is triggered by LA and pulmonary venous hypertension (reactive pulmonary hypertension); (3) interstitial edema in the walls of the small pulmonary vessels; and (4) at end stage, organic obliterative changes in the pulmonary vascular bed. Severe pulmonary hypertension results in RV enlargement, secondary tricuspid regurgitation (TR), and pulmonic regurgitation (PR), as well as right-sided heart failure.
In temperate climates, the latent period between the initial attack of rheumatic carditis (in the increasingly rare circumstances in which a history of one can be elicited) and the development of symptoms due to MS is generally about two decades; most patients begin to experience disability in the fourth decade of life. Studies carried out before the development of mitral valvotomy revealed that once a patient with MS became seriously symptomatic, the disease progressed inexorably to death within 2–5 years.
In patients whose mitral orifices are large enough to accommodate a normal blood flow with only mild elevations of LA pressure, marked elevations of this pressure leading to dyspnea and cough may be precipitated by sudden changes in the heart rate, volume status, or CO, as, for example, with severe exertion, excitement, fever, severe anemia, paroxysmal AF and other tachycardias, sexual intercourse, pregnancy, and thyrotoxicosis. As MS progresses, lesser degrees of stress precipitate dyspnea, the patient becomes limited in daily activities, and orthopnea and paroxysmal nocturnal dyspnea develop. The development of persistent AF often marks a turning point in the patient’s course and is generally associated with acceleration of the rate at which symptoms progress. Hemoptysis (Chap. 48) results from rupture of pulmonary-bronchial venous connections secondary to pulmonary venous hypertension. It occurs most frequently in patients who have elevated LA pressures without markedly elevated pulmonary vascular resistances and is rarely fatal. Recurrent pulmonary emboli (Chap. 300), sometimes with infarction, are an important cause of morbidity and mortality late in the course of MS. Pulmonary infections, i.e., bronchitis, bronchopneumonia, and lobar pneumonia, commonly complicate untreated MS, especially during the winter months.
In addition to the aforementioned changes in the pulmonary vascular bed, fibrous thickening of the walls of the alveoli and pulmonary capillaries occurs commonly in MS. The vital capacity, total lung capacity, maximal breathing capacity, and oxygen uptake per unit of ventilation are reduced (Chap. 306e). Pulmonary compliance falls further as pulmonary capillary pressure rises during exercise.
Thrombi may form in the left atria, particularly within the enlarged atrial appendages of patients with MS. Systemic embolization, the incidence of which is 10–20%, occurs more frequently in patients with AF, in patients >65 years of age, and in those with a reduced CO. However, systemic embolization may be the presenting feature in otherwise asymptomatic patients with only mild MS.
(See also Chaps. 51e and 267)
In patients with severe MS, there may be a malar flush with pinched and blue facies. In patients with sinus rhythm and severe pulmonary hypertension or associated tricuspid stenosis (TS), the jugular venous pulse reveals prominent a waves due to vigorous right atrial systole. The systemic arterial pressure is usually normal or slightly low. An RV tap along the left sternal border signifies an enlarged RV. A diastolic thrill may rarely be present at the cardiac apex, with the patient in the left lateral recumbent position.
The first heart sound (S1) is usually accentuated in the early stages of the disease and slightly delayed. The pulmonic component of the second heart sound (P2) also is often accentuated with elevated PA pressures, and the two components of the second heart sound (S2) are closely split. The opening snap (OS) of the mitral valve is most readily audible in expiration at, or just medial to, the cardiac apex. This sound generally follows the sound of aortic valve closure (A2) by 0.05–0.12 s. The time interval between A2 and OS varies inversely with the severity of the MS. The OS is followed by a low-pitched, rumbling, diastolic murmur, heard best at the apex with the patient in the left lateral recumbent position (see Fig. 267-5); it is accentuated by mild exercise (e.g., a few rapid sit-ups) carried out just before auscultation. In general, the duration of this murmur correlates with the severity of the stenosis in patients with preserved CO. In patients with sinus rhythm, the murmur often reappears or becomes louder during atrial systole (presystolic accentuation). Soft, grade I or II/VI systolic murmurs are commonly heard at the apex or along the left sternal border in patients with pure MS and do not necessarily signify the presence of MR. Hepatomegaly, ankle edema, ascites, and pleural effusion, particularly in the right pleural cavity, may occur in patients with MS and RV failure.
With severe pulmonary hypertension, a pansystolic murmur produced by functional TR may be audible along the left sternal border. This murmur is usually louder during inspiration and diminishes during forced expiration (Carvallo’s sign). When the CO is markedly reduced in MS, the typical auscultatory findings, including the diastolic rumbling murmur, may not be detectable (silent MS), but they may reappear as compensation is restored. The Graham Steell murmur of PR, a high-pitched, diastolic, decrescendo blowing murmur along the left sternal border, results from dilation of the pulmonary valve ring and occurs in patients with mitral valve disease and severe pulmonary hypertension. This murmur may be indistinguishable from the more common murmur produced by aortic regurgitation (AR), although it may increase in intensity with inspiration and is accompanied by a loud and often palpable P2.
In MS and sinus rhythm, the P wave usually suggests LA enlargement (see Fig. 268-8). It may become tall and peaked in lead II and upright in lead V1 when severe pulmonary hypertension or TS complicates MS and right atrial (RA) enlargement occurs. The QRS complex is usually normal. However, with severe pulmonary hypertension, right axis deviation and RV hypertrophy are often present.
(See also Chap. 270e) Transthoracic echocardiography (TTE) with color flow and spectral Doppler imaging provides critical information, including measurements of mitral inflow velocity during early (E wave) and late (A wave in patients in sinus rhythm) diastolic filling, estimates of the transvalvular peak and mean gradients and of the mitral orifice area, the presence and severity of any associated MR, the extent of leaflet calcification and restriction, the degree of distortion of the subvalvular apparatus, and the anatomic suitability for percutaneous mitral balloon valvotomy (percutaneous mitral balloon valvuloplasty [PMBV]; see below). In addition, TTE provides an assessment of LV and RV function, chamber sizes, an estimation of the PAP based on the tricuspid regurgitant jet velocity, and an indication of the presence and severity of any associated valvular lesions, such as aortic stenosis and/or regurgitation. Transesophageal echocardiography (TEE) provides superior images and should be used when TTE is inadequate for guiding management decisions. TEE is especially indicated to exclude the presence of LA thrombus prior to PMBV. The performance of TTE with exercise to evaluate the mean mitral diastolic gradient and PA pressures can be very helpful in the evaluation of patients with MS when there is a discrepancy between the clinical findings and the resting hemodynamics.
The earliest changes are straightening of the upper left border of the cardiac silhouette, prominence of the main PAs, dilation of the upper lobe pulmonary veins, and posterior displacement of the esophagus by an enlarged LA. Kerley B lines are fine, dense, opaque, horizontal lines that are most prominent in the lower and mid-lung fields and that result from distention of interlobular septae and lymphatics with edema when the resting mean LA pressure exceeds approximately 20 mmHg.
Like MS, significant MR may also be associated with a prominent diastolic murmur at the apex due to increased antegrade transmitral flow, but in patients with isolated MR, this diastolic murmur commences slightly later than in patients with MS, and there is often clear-cut evidence of LV enlargement. An OS and increased P2 are absent, and S1 is soft or absent. An apical pansystolic murmur of at least grade III/VI intensity as well as an S3 suggest significant MR. Similarly, the apical mid-diastolic murmur associated with severe AR (Austin Flint murmur) may be mistaken for MS but can be differentiated from it because it is not intensified in presystole and becomes softer with administration of amyl nitrite or other arterial vasodilators. TS, which occurs rarely in the absence of MS, may mask many of the clinical features of MS or be clinically silent; when present, the diastolic murmur of TS increases with inspiration and the y descent in the jugular venous pulse is delayed.
Atrial septal defect (Chap. 282) may be mistaken for MS; in both conditions, there is often clinical, ECG, and chest x-ray evidence of RV enlargement and accentuation of pulmonary vascularity. However, the absence of LA enlargement and of Kerley B lines and the demonstration of fixed splitting of S2 with a grade II or III mid-systolic murmur at the mid to upper left sternal border all favor atrial septal defect over MS. Atrial septal defects with large left-to-right shunts may result in functional TS because of the enhanced diastolic flow.
Left atrial myxoma (Chap. 289e) may obstruct LA emptying, causing dyspnea, a diastolic murmur, and hemodynamic changes resembling those of MS. However, patients with an LA myxoma often have features suggestive of a systemic disease, such as weight loss, fever, anemia, systemic emboli, and elevated serum IgG and interleukin 6 (IL-6) concentrations. The auscultatory findings may change markedly with body position. The diagnosis can be established by the demonstration of a characteristic echo-producing mass in the LA with TTE.
Left and right heart catheterization can be useful when there is a discrepancy between the clinical and noninvasive findings, including those from TEE and exercise echocardiographic testing as appropriate. Catheterization is helpful in assessing associated lesions, such as aortic stenosis (AS) and AR. Catheterization and coronary angiography are not usually necessary to aid in decision-making about surgery in patients younger than 65 years of age with typical findings of severe mitral obstruction on physical examination and TTE. In men older than 40 years of age, women older than 45 years of age, and younger patients with coronary risk factors, especially those with positive noninvasive stress tests for myocardial ischemia, coronary angiography is advisable preoperatively to identify patients with critical coronary obstructions that should be bypassed at the time of operation. Computed tomographic coronary angiography (CTCA) (Chap. 270e) is now often used to screen preoperatively for the presence of coronary artery disease (CAD) in patients with valvular heart disease and low pretest likelihood of CAD. Catheterization and left ventriculography may be useful in patients who have undergone PMBV or previous mitral valve surgery for MS, and who have redeveloped limiting symptoms, especially if questions regarding the severity of the valve lesion(s) remain after noninvasive study.
TREATMENT Mitral Stenosis
(Fig. 284-1) Penicillin prophylaxis of group A β-hemolytic streptococcal infections (Chap. 381) for secondary prevention of rheumatic fever is important for at-risk patients with rheumatic MS. Recommendations for infective endocarditis prophylaxis are similar to those for other valve lesions and are restricted to patients at high risk for complications from infection, including patients with a history of endocarditis. In symptomatic patients, some improvement usually occurs with restriction of sodium intake and small doses of oral diuretics. Beta blockers, nondihydropyridine calcium channel blockers (e.g., verapamil or diltiazem), and digitalis glycosides are useful in slowing the ventricular rate of patients with AF. Warfarin therapy targeted to an international normalized ratio (INR) of 2–3 should be administered indefinitely to patients with MS who have AF or a history of thromboembolism. The routine use of warfarin in patients in sinus rhythm with LA enlargement (maximal dimension >5.5 cm) with or without spontaneous echo contrast is more controversial. The novel oral anticoagulants are not approved for use in patients with significant valvular heart disease.
If AF is of relatively recent onset in a patient whose MS is not severe enough to warrant PMBV or surgical commissurotomy, reversion to sinus rhythm pharmacologically or by means of electrical countershock is indicated. Usually, cardioversion should be undertaken after the patient has had at least 3 consecutive weeks of anticoagulant treatment to a therapeutic INR. If cardioversion is indicated more urgently, then intravenous heparin should be provided and TEE performed to exclude the presence of LA thrombus before the procedure. Conversion to sinus rhythm is rarely successful or sustained in patients with severe MS, particularly those in whom the LA is especially enlarged or in whom AF has been present for more than 1 year. MITRAL VALVOTOMY
Unless there is a contraindication, mitral valvotomy is indicated in symptomatic (New York Heart Association [NYHA] Functional Class II–IV) patients with isolated severe MS, whose effective orifice (valve area) is < ~1 cm2/m2 body surface area, or <1.5 cm2 in normal-sized adults. Mitral valvotomy can be carried out by two techniques: PMBV and surgical valvotomy. In PMBV (Figs. 284-2 and 284-3), a catheter is directed into the LA after transseptal puncture, and a single balloon is directed across the valve and inflated in the valvular orifice. Ideal patients have relatively pliable leaflets with little or no commissural calcium. In addition, the subvalvular structures should not be significantly scarred or thickened, and there should be no LA thrombus. The short- and long-term results of this procedure in appropriate patients are similar to those of surgical valvotomy, but with less morbidity and a lower periprocedural mortality rate. Event-free survival in younger (<45 years) patients with pliable valves is excellent, with rates as high as 80–90% over 3–7 years. Therefore, PMBV has become the procedure of choice for such patients when it can be performed by a skilled operator in a high-volume center.
TTE is helpful in identifying patients for the percutaneous procedure, and TEE is performed routinely to exclude LA thrombus and to assess the degree of MR at the time of the scheduled procedure. An “echo score” has been developed to help guide decision-making. The score accounts for the degree of leaflet thickening, calcification, and mobility, and for the extent of subvalvular thickening. A lower score predicts a higher likelihood of successful PMBV.
In patients in whom PMBV is not possible or unsuccessful, or in many patients with restenosis after previous surgery, an “open” valvotomy using cardiopulmonary bypass is necessary. In addition to opening the valve commissures, it is important to loosen any subvalvular fusion of papillary muscles and chordae tendineae; to remove large deposits of calcium, thereby improving valvular function; and to remove atrial thrombi. The perioperative mortality rate is ~2%.
Successful valvotomy is defined by a 50% reduction in the mean mitral valve gradient and a doubling of the mitral valve area. Successful valvotomy, whether balloon or surgical, usually results in striking symptomatic and hemodynamic improvement and prolongs survival. However, there is no evidence that the procedure improves the prognosis of patients with slight or no functional impairment. Therefore, unless recurrent systemic embolization or severe pulmonary hypertension has occurred (PA systolic pressures >50 mmHg at rest or >60 mmHg with exercise), valvotomy is not recommended for patients who are entirely asymptomatic and/or who have mild or moderate stenosis (mitral valve area >1.5 cm2). When there is little symptomatic improvement after valvotomy, it is likely that the procedure was ineffective, that it induced MR, or that associated valvular or myocardial disease was present. About half of all patients undergoing surgical mitral valvotomy require reoperation by 10 years. In the pregnant patient with MS, valvotomy should be carried out if pulmonary congestion occurs despite intensive medical treatment. PMBV is the preferred strategy in this setting and is performed with TEE and no or minimal x-ray exposure.
Mitral valve replacement (MVR) is necessary in patients with MS and significant associated MR, those in whom the valve has been severely distorted by previous transcatheter or operative manipulation, or those in whom the surgeon does not find it possible to improve valve function significantly with valvotomy. MVR is now routinely performed with preservation of the chordal attachments to optimize LV functional recovery. Perioperative mortality rates with MVR vary with age, LV function, the presence of CAD, and associated comorbidities. They average 5% overall but are lower in young patients and may be twice as high in patients >65 years of age with significant comorbidities (Table 284-2). Because there are also long-term complications of valve replacement, patients in whom preoperative evaluation suggests the possibility that MVR may be required should be operated on only if they have severe MS—i.e., an orifice area ≤1.5 cm2—and are in NYHA Class III, i.e., symptomatic with ordinary activity despite optimal medical therapy. The overall 10-year survival of surgical survivors is ~70%. Long-term prognosis is worse in patients >65 years of age and those with marked disability and marked depression of the CO preoperatively. Pulmonary hypertension and RV dysfunction are additional risk factors for poor outcome.
Management of rheumatic mitral stenosis. See legend for Fig. 283-2 for explanation of treatment recommendations (class I, IIa, IIb) and disease stages (C, D). Preoperative coronary angiography should be performed routinely as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography may also be helpful when there is a discrepancy between clinical and noninvasive findings. AF, atrial fibrillation; LA, left atrial; MR, mitral regurgitation; MS, mitral stenosis; MVA, mitral valve area; MVR, mitral valve surgery (repair or replacement); NYHA, New York Heart Association; PCWP, pulmonary capillary wedge pressure; PMBC, percutaneous mitral balloon commissurotomy; and T ½, pressure half-time. (Adapted from RA Nishimura et al: 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease. J Am Coll Cardiol doi: 10.1016/j.jacc.2014.02.536, 2014, with permission.)
Inoue balloon technique for percutaneous mitral balloon valvotomy. A. After transseptal puncture, the deflated balloon catheter is advanced across the interatrial septum, then across the mitral valve and into the left ventricle. B–D. The balloon is inflated stepwise within the mitral orifice.
Simultaneous left atrial (LA) and left ventricular (LV) pressure before and after percutaneous mitral balloon valvuloplasty (PMBV) in a patient with severe mitral stenosis. ECG, electrocardiogram. (Courtesy of Raymond G. McKay, MD; with permission.)