SympoSIUm on cARDIoVAScULAR VALVULAR DISEASES HEART DISEASE

Valvular Heart Disease: Diagnosis and Management Kameswari Maganti, MD; Vera H. Rigolin, MD; Maurice Enriquez Sarano, MD; and Robert O. Bonow, MD On completion of this article, you should be able to (1) summarize important basic and clinical concepts of valvular heart disease, (2) recognize the full array of valvular disorders so as to provide enhanced care for patients with valvular heart disease, and (3) treat patients in accordance with new recommendations from recent clinical trials and clinical practice guidelines. Valvular heart disease (VHD) encompasses a number of common cardiovascular conditions that account for 10% to 20% of all cardiac surgical procedures in the United States. A better understanding of the natural history coupled with the major advances in diagnostic imaging, interventional cardiology, and surgical approaches have resulted in accurate diagnosis and appropriate selection of patients for therapeutic interventions. A thorough understanding of the various valvular disorders is important to aid in the management of patients with VHD. Appropriate work-up for patients with VHD includes a thorough history for evaluation of causes and symptoms, accurate assessment of the severity of the valvular abnormality by examination, appropriate diagnostic testing, and accurate quantification of the severity of valve dysfunction and therapeutic interventions, if necessary. It is also important to understand the role of the therapeutic interventions vs the natural history of the disease in the assessment of outcomes. Prophylaxis for infective endocarditis is no longer recommended unless the patient has a history of endocarditis or a prosthetic valve. Mayo Clin Proc. 2010;85(5):483-500 AR = aortic regurgitation; AS = aortic stenosis; AVR = aortic valve replacement; CAD = coronary artery disease; CMR = cardiac magnetic resonance imaging; CT = computed tomography; ECG = electrocardiography; LV = left ventricular; MR = mitral regurgitation; MS = mitral stenosis; MV = mitral valve; RV = right ventricular

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egenerative valve disease is the most common form of valvular heart disease in the United States, whereas rheumatic heart disease accounts for most valve pathology in developing nations. As the US population ages, physicians are likely to see more patients with degenerative valve disorders. Because people continue to immigrate to the United States from developing nations, rheumatic valve disease may be seen more frequently. Thus, an understanding of the full array of valvular disorders is imperative to the provision of quality patient care. AORTIC STENOSIS Etiology and PathoPhysiology Aortic stenosis (AS) is the most prevalent form of cardiovascular disease in the Western world after hypertension and coronary artery disease. It is usually caused by either degenerative calcification of a trileaflet valve or progressive stenosis of a congenital bicuspid valve. Rheumatic Mayo Clin Proc.

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heart disease, the most common etiology worldwide, is less common in the United States. Aortic stenosis develops from progressive calcification of leaflets with restriction of leaflet opening over time. The risk factors for the development of degenerative calcific AS, which are similar to those for the development of vascular atherosclerosis, include diabetes, hypertension, smoking, and elevated levels of low-density lipoprotein cholesterol and lipoprotein(a).1 Obstruction of left ventricular (LV) outflow can also occur at the subvalvular level (discrete subvalvular obstruction, hypertrophic cardiomyopathy) or above the valve (supravalvular stenosis). In patients with valvular AS, the severity of stenosis increases gradually over many years. The left ventricle adapts to the obstruction by increasing wall thickness while maintaining normal LV chamber size (concentric hypertrophy). The development of hypertrophy is a compensatory mechanism to normalize the LV wall stress and appears to be a critical determinant of ventricular performance in patients with AS. Left ventricular systolic function is usually preserved, and cardiac output is maintained for many years despite the pressure gradient across the aortic valve. In many patients, this compensatory mechanism cannot be maintained indefinitely, and systolic function begins to decline as a result of the pressure overload. If LV systolic dysfunction is present, it often improves after aortic valve replacement (AVR). However, LV function will not improve if myocardial contractile dysfunction is irreversible.2 Differentiation between reversible and irreversible LV dysfunction is not possible on the basis of a preoperative resting imaging study alone. From the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (K.M., V.H.R., R.O.B.); and Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (M.E.S.). Address correspondence to Kameswari Maganti, MD, Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, 201 E Huron St, Ste 11-240, Chicago, IL 60611 ([email protected]). Individual reprints of this article and a bound reprint of the entire Symposium on Cardiovascular Diseases will be available for purchase from our Web site www.mayoclinicproceedings.com. © 2010 Mayo Foundation for Medical Education and Research

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Concentric hypertrophy as an adaptive response to obstruction can also be maladaptive. As stenosis severity progresses, the left ventricle becomes less compliant and the LV diastolic pressure increases even though the ventricular size is normal. Thus, dyspnea on exertion may result from LV systolic dysfunction or elevated diastolic filling pressures with preserved systolic function. The increased wall thickness can also lead to reduced coronary artery blood flow per gram of muscle and reduced coronary flow reserve, resulting in angina pectoris even if the epicardial coronary arteries are normal. Eventually, with progression of stenosis severity, symptoms of angina (35% of patients), syncope (15% of patients), or dyspnea and/or heart failure (50% of patients) develop.3 The symptoms are typically noted with exertion. Once symptoms develop, prompt surgical intervention is needed because the average survival is only 2 to 3 years with an increased risk of sudden death.4,5 Therefore, careful history regarding the onset of symptoms is essential. Prognosis of patients with asymptomatic severe AS is more difficult to determine; however, AS is a progressive disease, and so patients with severe AS have a high likelihood of developing symptoms in the course of 3 to 5 years.6 Atrial fibrillation in particular is tolerated poorly in patients with severe AS because the loss of atrial contraction as well as the rapid ventricular response limits diastolic filling of the left ventricle. Physical Examination The spectrum of findings on physical examination varies with the severity of valve calcification, the severity of stenosis, and LV function. In general, in patients with severe AS the arterial pulse is slow to increase and has a reduced peak (pulsus parvus et tardus), which is best appreciated by palpating the carotid pulse. This may not be present in elderly patients because of the rigidity of the vasculature. The carotid pulse may also demonstrate a systolic thrill. The jugular venous pulse is usually normal, but prominent a waves may be present, reflecting reduced right ventricular (RV) compliance due to hypertrophy of the interventricular septum. The v wave may be prominent if there is RV failure. The apical cardiac impulse is usually normal in location unless LV dysfunction has developed but is often sustained in nature because of LV hypertrophy. The S1 is usually normal or soft. The S2 may be single because the aortic and pulmonic valve components are superimposed, or the aortic valve component is absent or soft because the aortic valve is calcified and immobile. An S4 may be palpable and audible because of a vigorous atrial contraction. Presence of an S4 in a young patient with AS is a marker of LV hypertrophy and typically indicates that the AS is severe in the absence of other disorders that could lead to LV hypertrophy. 484

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The characteristic murmur of AS is a crescendo-decrescendo systolic murmur along the left sternal border that radiates to the upper right sternal border and into the carotid arteries. However, it may also radiate to the LV apex (the Gallavardin phenomenon) and may be mistaken for a murmur of mitral regurgitation (MR). The intensity of the murmur does not correspond to the severity of AS. As the severity of the AS increases, the duration of the murmur increases, and it is more likely to peak at mid to late systole. A diastolic murmur may be heard if aortic regurgitation (AR) is also present, a characteristic finding in patients with rheumatic AS. In young patients with bicuspid AS, the systolic murmur may be preceded by a systolic ejection click. This sound tends to disappear with aging as the valve calcifies and the severity of AS increases. In the presence of severe heart failure, the apical impulse may be diffuse and laterally displaced, a third heart sound may be present, the jugular venous pulse may be elevated, and the systolic murmur may be soft or absent.1,7 diagnostic tEsting Chest Radiography. Cardiac size is often normal in patients with AS, with rounding of the LV border and apex due to the LV hypertrophy. Aortic valve and aortic root calcification are best appreciated in the lateral projections on fluoroscopy. They are rarely detected on anteroposterior or posteroanterior projections. The proximal ascending aorta may be dilated, particularly in patients with bicuspid valves. Cardiomegaly is a late feature in patients with AS. In patients with heart failure, the heart is enlarged, with congestion of pulmonary vasculature. In cases of advanced heart failure, the right atrium and right ventricle may also be enlarged. Electrocardiography. The typical finding on electrocardiography (ECG) in patients with AS is LV hypertrophy, often with secondary repolarization abnormalities. This is found in 85% of patients with severe AS. However, its absence does not preclude AS. Left atrial enlargement and conduction abnormalities are also common, including left and right bundle branch block. This may be due to extension of the calcification into the surrounding conduction system. The axis may be shifted leftward or rightward. Atrial fibrillation can also develop, particularly in older patients and those with hypertension. A sample ECG from a patient with AS is shown in Figure 1. Echocardiography. Echocardiography is the imaging modality of choice to help diagnose and estimate the severity of AS. Two-dimensional echocardiography demonstrates the morphology of the aortic valve and can often delineate if it is trileaflet or bicuspid. The spectrum of calcific aortic valve disease ranges from aortic sclerosis without obstruction to ventricular outflow to severe AS. Aortic

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VALVULAR HEART DISEASE

FIGURE 1. Electrocardiogram of a patient with severe aortic stenosis showing marked left ventricular hypertrophy with repolarization abnormalities.

sclerosis is common and is often seen in people older than 65 years. On echocardiography, it is characterized by focal areas of valve thickening, typically located in the leaflet center with commissural sparing and normal leaflet mobility. Diffuse leaflet thickening is not characteristic of aortic sclerosis; instead, it suggests normal aging changes, a different valvular pathology, or an imaging artifact. With aortic sclerosis, valvular hemodynamics are within normal limits, with an aortic valve velocity of less than 2.5 m/s.8,9 Several studies have documented clinical factors associated with calcific aortic valve disease that are similar to atherosclerotic heart disease, with an increase in cardiovascular morbidity and mortality.10-14 In patients with AS, the aortic valve is usually thickened and calcified, with limited excursion and a reduced aortic valve area (Figure 2). Doming of the aortic leaflets due to asymmetry and restriction is often seen in young patients with bicuspid aortic valves. The ascending aorta should also be evaluated and measured to detect associated aortic aneurysms, which are particularly common in patients with bicuspid valves. In the absence of heart failure, the LV cavity is usually of normal size or small. Left ventricular hypertrophy is often present, as is left atrial enlargement. Left ventricular systolic function is usually normal. If heart failure has developed, the left ventricle may be enlarged and systolic function depressed. Doppler echocardiography is an excellent tool for both evaluating the severity of AS by measuring jet velocity and gradients and calculating the aortic valve area. It also aids in detecting other associated valve lesions and in estimating pulmonary artery systolic pressure. The classification Mayo Clin Proc.

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of the severity of AS on the basis of findings on Doppler echocardiography is shown in Table 1.8 As the aortic valve area decreases with time, the velocity of forward flow across the valve increases. This hallmark of AS is one of the principal means of assessing the severity of AS with echocardiography, which has largely obviated the need for cardiac catheterization for hemodynamic assessment. Assessing the severity of AS using Doppler criteria is dependent not only on the severity of AS but also on the aortic flow. In patients with low cardiac output, such as patients with LV dysfunction, the calculated gradients and aortic valve area may not be representative of the

FIGURE 2. Parasternal short-axis echocardiographic view of a patient with severe aortic stenosis due to a congenital bicuspid aortic valve. The leaflets are heavily calcified (arrow).

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TABLE 1. Classification of Aortic Stenosis Severity Using Doppler Examination Aortic sclerosis Mild Moderate Severe Aortic jet velocity (m/s) Mean gradient (mm Hg) Aortic valve area (cm2) Indexed aortic valve area (cm2/m2) Velocity ratio

≤2.5 … …

2.6-2.9 1.5 >0.85 >0.50

3.0-4.0 20-40b (30-50a) 1.0-1.5 0.60-0.85 0.25-0.50

>4.0 >40b (>50a) 55 mm or DD >75 mm

LV dimensions?

Class IIb SD 90%. Adapted from Circulation.2

MR and normal LV function, repair of a severely regurgitant valve may be contemplated to prevent sequelae of chronic severe MR. This should be considered only when the likelihood of successful valve repair is greater than 90% in an experienced center.2 In patients with functional MR associated Mayo Clin Proc.

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with LV dysfunction, angiotensin-converting enzyme inhibitors, β-blockers, and biventricular pacing have been shown to produce beneficial reverse remodeling, and the reduction in LV end-diastolic and end-systolic volumes with these therapies is associated with decreased severity of MR. 39-41

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TABLE 2. Classification of Mitral Stenosis Severity

Specific findings Valve area (cm2) Supportive findings Mean gradient (mm Hg)a Pulmonary artery pressure (mm Hg)

Mild

Moderate

Severe

>1.5

1.0-1.5

50 mm Hg at rest) should be considered for percutaneous balloon valvotomy. Patients with severe MR, severely thickened or highly calcified MV leaflets, and/or subvalvular apparatus are not optimal can didates for this procedure. Symptoms may be difficult to ascertain in patients who are sedentary. In such patients, exercise testing with the assessment of the MV gradient and pulmonary artery pressures before and after exercise may be useful in determining the possible cardiac etiology of symptoms.2 Surgical valve replacement should be considered for patients who are not candidates for percutaneous intervention. The management strategy for MS is outlined in Figure 15.2 SPECIAL POPULATIONS PrEgnancy Important hemodynamic changes occur during pregnancy. Plasma volume increases during the first trimester and can reach as high as 50% above baseline by the second trimester. Plasma volume then plateaus for the rest of the pregnancy. The heart rate increases 10 to 20 beats/min above baseline. Uterine contraction and endogenous hormones result in a decline in peripheral vascular resistance and a widening of the pulse pressure. The gravid uterus can obstruct the inferior vena cava, potentially resulting in peripheral edema, weakness, and hypotension. The added volume load may result in symptoms of dyspnea and heart failure in women with impaired LV function and those with limited cardiac reserve. Stenotic valvular lesions are less well tolerated than regurgitant ones. The increased heart rate associated with pregnancy reduces the

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Mitral stenosis

Yes

MVA ≥1.5 cm2

MVA 50 mm Hg or Exercise PAP >60 mm Hg or new-onset AF

No

No

No

Symptoms?

Yes

Class IIa Class I

Class IIb

New-onset AF? No No

Class I

No

Clinical follow-up Annual echocardiography

PMBV (no LA clot, MR ≤2+)

FIGURE 15. Management strategy for patients with severe mitral stenosis. AF = atrial fibrillation; LA = left atrial; MR = mitral regurgitation; MV = mitral valve; MVA = MV area; PAP = pulmonary artery pressure; PMBV = percutaneous mitral balloon valvotomy. Adapted from Circulation.2

time for diastolic filling, which can be extremely troublesome for many patients, especially those with MS.30 It is not uncommon for women with MS to first come to clinical attention during pregnancy. During delivery, uterine contraction results in up to 500 mL of blood being released into the circulation. During a normal vaginal delivery, the woman loses approximately 400 mL of blood. The risk of blood loss during a cesarean section is often greater, averaging about 800 mL. There is an abrupt increase in venous return after delivery, due to autotransfusion from the uterus and because the baby no longer compresses the inferior vena cava. In addition, there continues to be autotransfusion of blood for 24 to 72 hours after delivery. Thus, the risk of pulmonary edema extends for several days after delivery.44 High-risk valvular lesions associated with pregnancy are listed in Table 3. Patients with moderate to severe valve lesions should be referred to a cardiovascular specialist for assistance in the care of the patient during the pregnancy and delivery. Ideally, the risks of surgery should be discussed with the patient before conception. 498

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Women with mechanical prosthetic valves pose unique challenges during pregnancy. The anticoagulation management of a pregnant woman with a mechanical prosthetic valve is controversial2; the patient should discuss it in detail with a cardiovascular specialist, preferably before conception. ProsthEtic ValVEs In patients who require valve replacement surgery, the selection of a mechanical prosthesis vs a bioprosthesis must be individualized and requires a detailed discussion with the patient. Age, lifestyle, and medical comorbid conditions are the most important considerations in making this selection. Although the durability of mechanical valves is greater than that of tissue valves, patients with mechanical valves must be treated with life-long warfarin, with the addition of aspirin unless contraindicated. Mechanical mitral prostheses are more thrombogenic than those in the aortic position. The durability of a bioprosthesis increases as a function of age,45 and thus a bioprosthesis is a reasonable choice in patients older than 65 years.2 Many patients younger than 65 years will select a bioprosthesis for lifestyle considerations, with

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TABLE 3. Valvular Heart Lesions Associated With High Maternal and/or fetal Risk During Pregnancy Severe aortic stenosis with or without symptoms Aortic regurgitation with NYHA functional class III-IV symptoms Mitral stenosis with NYHA functional class II-IV symptoms Mitral regurgitation with NYHA functional class III-IV symptoms Aortic and/or mitral valve disease resulting in severe pulmonary hypertension (pulmonary pressure >75% of systemic pressures) Aortic and/or mitral valve disease with severe LV dysfunction (LVEF