36 - 274 Mitral Stenosis

274 Mitral Stenosis

Patrick T. O’Gara, Joseph Loscalzo

Mitral Stenosis PART 6 Disorders of the Cardiovascular System The role of the physical examination in the evaluation of patients with valvular heart disease is also considered in Chaps. 44 and 246; of elec­ trocardiography (ECG) in Chap. 247; of echocardiography and other noninvasive imaging techniques in Chap. 248; and of cardiac catheter­ ization and angiography in Chap. 249. MITRAL STENOSIS ■ ■ETIOLOGY AND PATHOLOGY Rheumatic fever is the leading cause of mitral stenosis (MS) (Table 274-1; see also Chap. 371). 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 ~40% of all patients with rheumatic heart disease and a history of rheumatic fever (Chap. 371). 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 middle- to high-income countries, the incidence of MS has declined considerably over the past several decades. However, it remains a major problem in low-income countries, especially in subSaharan Africa, India, Southeast Asia, and Oceania (Chap. 272). In rheumatic MS, chronic inflammation leads to diffuse thicken­ ing of the valve leaflets with formation of fibrous tissue often with calcific deposits. The mitral commissures fuse, the chordae tendineae fuse and shorten, the valvular cusps become rigid, and the pathologic process eventually leads 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 inflammation, fibrosis, and trauma 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. ■ ■PATHOPHYSIOLOGY 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 TABLE 274-1  Major Causes of Mitral Stenosis Etiologies Rheumatic fever Congenital (parachute valve, cor triatriatum) Severe mitral annular calcification with leaflet involvement SLE, RA Myxoma IE with large vegetations Abbreviations: IE, infective endocarditis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus.

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. 249). 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, includ­ ing 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 (TS). 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. Cardiac Output  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. Pulmonary Hypertension  The clinical and hemodynamic fea­ tures of MS are influenced importantly by the level of the PAP. Pul­ monary 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. ■ ■SYMPTOMS 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 surgical mitral valvotomy revealed that once a patient with MS became seriously symptomatic, the disease progressed inexo­ rably 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 precip­ itated by sudden changes in the heart rate, volume status, or CO, as, for example, with severe exertion, excitement, fever, severe anemia, parox­ ysmal 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 orthop­ nea 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. 41) results from rupture of pulmonarybronchial venous connections secondary to pulmonary venous hyper­ tension. 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. 290), sometimes with infarction, are an important cause of morbidity and mortality late in the course of MS and often arise from right atrial mural thrombus. Pulmonary infections, i.e., bronchitis, bronchopneumonia, and lobar pneumonia, commonly complicate untreated MS, especially during the winter months. In patients with significant left atrial enlargement,

cardiovocal syndrome (Ortner’s syndrome) may develop with hoarse­ ness secondary to left recurrent laryngeal nerve compression. Pulmonary Changes  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. 296). Pulmonary compliance falls further as pulmonary capillary pressure rises during exercise. Thrombi and Emboli  Thrombi may form in the left atria, par­ ticularly 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 pre­ senting feature in otherwise asymptomatic patients with only mild MS. ■ ■PHYSICAL FINDINGS (See also Chaps. 44 and 246). Inspection and Palpation  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 TS, the jugu­ lar venous pulse reveals prominent a waves due to vigorous right atrial systole. The systemic arterial pressure is usually normal or slightly low. A parasternal lift signifies an enlarged RV. A diastolic thrill may very rarely be present at the cardiac apex, with the patient in the left lateral recumbent position. Auscultation  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 PAPs, 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. 246-5); 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 mur­ murs may be heard at or medial to the apex and may signify mixed mitral valve disease with regurgitation. Hepatomegaly, ankle edema, ascites, and pleural effusion, particularly in the right pleural cavity, may occur in patients with MS and RV failure. Associated Lesions  With severe pulmonary hypertension, a pan­ systolic 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 pul­ monary valve ring and occurs in patients with mitral valve disease and severe pulmonary hypertension. This murmur may be indistinguish­ able from the more common murmur produced by aortic regurgita­ tion (AR), although it may increase in intensity with inspiration and is accompanied by a loud and often palpable P2. ■ ■LABORATORY EXAMINATION ECG  In MS and sinus rhythm, the P wave usually suggests LA enlargement (see Fig. 247-8). It may become tall and peaked in lead II and upright in lead V1 when severe pulmonary hypertension or TS

CHAPTER 274 Mitral Stenosis FIGURE 274-1  Continuous wave Doppler interrogation of transmitral valve velocities in a patient with severe rheumatic mitral stenosis. Electrocardiogram on top. Vertical scale in meters/second. Horizontal scale in seconds at sweep speed of 75 mm/se. Velocity is converted to pressure using the Bernoulli equation. In this example, the mean mitral valve gradient (area under the green tracing) is calculated to 38 mmHg and mitral valve area to 0.7 cm2. complicates MS and right atrial (RA) enlargement develops. The QRS complex is usually normal. However, with severe pulmonary hyperten­ sion, right axis deviation and RV hypertrophy are often present. Echocardiogram (See also Chap. 248)  Transthoracic echo­ cardiography (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 mitral orifice area (Fig. 274-1), 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 commissurotomy (PMBC; see below). In addition, TTE provides an assessment of LV and RV function, chamber sizes, an estimation of the PA systolic pressure based on the tricuspid regurgitant jet velocity, and an indication of the presence and severity of any associated valvular lesions, such as aortic stenosis (AS) and/or regurgitation. Transesophageal echocardiogra­ phy (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 PMBC. The performance of TTE with exercise to evaluate the mean mitral diastolic gradient, PAPs, and RV function can be very helpful in the evaluation of patients with MS when there is a discrepancy between the clinical findings and the resting hemodynamics. Chest X-Ray  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 that result from distention of interlobular septae and lymphatics with edema when the resting mean LA pressure exceeds ~20 mmHg. ■ ■DIFFERENTIAL DIAGNOSIS Like MS, significant MR may also be associated with a prominent dia­ stolic 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 suggests 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 pre-systole and becomes softer with administra­ tion 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. 280) 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 demonstra­ tion 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. An incomplete right bundle branch block pattern on ECG is often present. PART 6 Disorders of the Cardiovascular System Left atrial myxoma (Chap. 282) 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) con­ centrations. 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. ■ ■CARDIAC CATHETERIZATION Left and right heart catheterization can be useful when there is a discrepancy between the clinical and noninvasive findings, includ­ ing those from TEE and exercise echocardiographic testing when appropriate. Catheterization can also be helpful in assessing associated lesions, such as AS and AR, and in patients with recurring or worsening symptoms late after mitral valve intervention. Computed tomographic coronary angiography is increasingly used to screen preoperatively for Severe MS MVA ≤1.5 cm2 Symptomatic Stage D Severe symptoms NYHA III–IV No Pliable valve No clot <2+ MR Surgical candidate Yes Yes No PMBC at CVC (1) MV surgery (1) FIGURE 274-2  Management of rheumatic mitral stenosis. See legend for Fig. 272-4 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; CVC, comprehensive valve center; MR, mitral regurgitation; MS, mitral stenosis; MV, mitral valve; MVA, mitral valve area; MVR, mitral valve surgery (repair or replacement); NYHA, New York Heart Association; PASP, pulmonary arterial systolic pressure; PMBC, percutaneous mitral balloon commissurotomy. (Reproduced with permission from CM Otto et al: ACC/AHA guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 143:e72, 2021.)

the presence of coronary artery disease in appropriate patients prior to heart valve surgery or transcatheter treatment. TREATMENT Mitral Stenosis (Fig. 274-2) Penicillin prophylaxis of group A β-hemolytic streptococcal infec­ tions (Chap. 371) for secondary prevention of rheumatic fever is important for at-risk patients with rheumatic MS. Recommenda­ tions 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 his­ tory of endocarditis. In symptomatic patients, some improvement usually occurs with restriction of sodium intake and small doses of oral diuretics. Beta blockers, nondihydropyridine calcium chan­ nel blockers (e.g., verapamil or diltiazem), and digitalis glycosides are useful in slowing the ventricular rate of patients with AF. Vitamin K antagonist therapy (such as warfarin) targeted to an international normalized ratio (INR) of 2–3 should be adminis­ tered indefinitely to patients with MS who have AF, a history of thromboembolism, or demonstrated LA thrombus. The routine use of a vitamin K antagonist in patients in sinus rhythm with LA enlargement (maximal dimension >5.5 cm) with or without spon­ taneous echo contrast is more controversial. In a randomized trial of patients with rheumatic MS and AF, there was a significantly higher incidence of death among patients treated with rivaroxaban than with vitamin K antagonist therapy. A vitamin K antagonist is Rheumatic mitral stenosis Progressive MS MVA >1.5 cm2 Asymptomatic Stage C Exertional symptoms Pliable valve No clot <2+ MR Stress test Hemodynamically significant MS New AF PASP

50 mmHg Pliable valve No clot <2+ MR PMBC at CVC (2b) PMBC at CVC (2b) PMBC at CVC (2a)

recommended to reduce the risk for stroke or systemic embolism in at-risk patients with rheumatic MS. If AF is of relatively recent onset in a patient whose MS is not severe enough to warrant PMBC or surgical intervention, reversion to sinus rhythm pharmacologically or by means of electrical coun­ tershock is indicated. Usually, cardioversion should be undertaken after the patient has had at least 3 consecutive weeks of anticoagu­ lant 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 significantly enlarged or in whom AF has been present for

1 year, conditions that favor the development of an LA myopathy. MITRAL COMMISSUROTOMY Unless there is a contraindication, mitral commissurotomy is indi­ cated in symptomatic (New York Heart Association [NYHA] func­ tional 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 commissurotomy can be carried out either percutaneously or surgically. In PMBC (Figs. 274-3 and 274-4), a catheter is directed into the LA after transseptal punc­ ture, 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. Any associated MR should be of ≤2+/4+ severity. The short- and long-term results of this procedure in appropriate patients are similar to those of surgical commissur­ otomy, 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, PMBC is the procedure of choice for such patients when it can be performed by a skilled operator in a high-volume center. Guide wire Stiffening cannula B A D C FIGURE 274-3  Inoue balloon technique for percutaneous mitral balloon commissurotomy. 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.

PREDILATATION POSTDILATATION ECG ECG CHAPTER 274 LV LV

Pressure (mmHg) Mitral Stenosis LA LA

Mean mitral gradient 3 mmHg Cardiac output 3.8 L/min Mitral valve area 1.8 cm2 Mean mitral gradient 15 mmHg Cardiac output 3 L/min Mitral valve area 0.6 cm2 FIGURE 274-4  Simultaneous left atrial (LA) and left ventricular (LV) pressure before and after percutaneous mitral balloon commissurotomy (PMBC) in a patient with severe mitral stenosis. ECG, electrocardiogram. (Courtesy of Raymond G. McKay, MD.) TTE is helpful in identifying patients for the percutaneous pro­ cedure; 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 PMBC. In patients in whom PMBC is not possible or unsuccessful, or in many patients with restenosis after previous surgery, an “open” surgical commissurotomy using cardiopulmonary bypass is neces­ sary. 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 for this type of mitral valve repair procedure is ~2%. Successful commissurotomy is defined by a 50% reduction in the mean mitral valve gradient and a doubling of the mitral valve area. Successful commissurotomy, whether balloon or surgical, usually results in striking symptomatic and hemodynamic improvement and prolongs survival. However, there is no evidence that the proce­ dure 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), commissurotomy is not recommended for patients who are asymptomatic and/or who have mild or moderate stenosis (mitral valve area >1.5 cm2). When there is little symptomatic improvement after commissurotomy, 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 commissurotomy require reoperation by 10 years. In the pregnant patient with MS, commissurotomy should be carried out if pulmonary congestion occurs despite intensive medical treatment. PMBC is the preferred strategy in this setting and is performed with TEE and no or mini­ mal 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 pos­ sible to improve valve function significantly with commissurotomy. MVR is now routinely performed with preservation of the chordal attachments to optimize LV functional recovery. Perioperative mor­ tality rates with MVR vary with age, LV function, the presence of CAD, and associated comorbidities. They average 2–5% overall but