CHAPTER 4 Valvular heart disease 174 General considerations Development Cardiac valves develop from the mesodermal germ layer be tween the fourth and seventh weeks of gestation. Factors affecting embryogen- esis during t his time can in \202 uence valve development, such as infection (rubella) or drugs. Anatomy The human heart contains four valves: two on the left side of the heart (mitral and aortic) and two on the right (tricuspid and pulmonic, or pul- monary) (Fig. 4.1). The mitral and tricuspid valves, also referred to as atrioventricular (AV) valves, are supp orted by a \201 brous skeleton and separate the atrial and ventricular chambers, ensuring unidirectional \202 ow of blood during dias- tole. The mitral valve is composed of two l ea \202 ets (anterior and poste- rior) while the tricuspid valve (as the name implies) con tains three lea \202 ets (anterior, posterior, and septal). Both the mitral and tricuspid valve lea \202 ets are attached by chordae tendinae to papil lary muscles in their respective ventricles, the contrac- tion of which ensures valve compe tency. The aortic and pulmonic valves, also referred to as semilunar valves, separate the left and right ventricles from the aorta and pulmonary artery, respectively, ensuring unidirectiona l forward blood \202 ow during systole. The aortic and pulmonic valves each contain three cusps. GENERAL CONSIDERATIONS 175 Superior vena cava Aorta Pulmonary artery Pulmonary vein Left atrium Right atrium Mitral valve Left ventricle Pulmonary valve Aortic valve Right ventricle Tricuspid valve Inferior vena cava Figure 4.1 Heart valves as viewed from above with the atria removed (top) and in a coronal section (bottom). CHAPTER 4 Valvular heart disease 176 Acute rheumatic fever Epidemiology In the United States and other developed countries, the incidence is 2 to 14 cases per 100,000, with around 10 cases per 1000 school children in de veloping countries. Although it is now rare in the developed world, it still accounts for a lmost half of all cardiac disease in the developing world. Declining incidence in the developed world is likely due to improved economic standards and housing conditions, decreased crowding in houses and schools, improved access to medical c are, and effective antimicrobials, especially penicillin. Those affected are typically children aged 5 \200\22315 years from lower socio- economic cl ass living in crowded conditions; 20% of cases occur in adults. There is no gender differen ce in incidence, but chorea and mitral steno- sis (MS) are more common in females. Pathology \200 \200 It typically occurs several weeks after streptococcal pharyngitis. The most common pathogen is group A beta-hemolytic streptococci (Streptococcus pyogenes serotype M). Antigenic mimi cry is implicated in the pathogenesis as antibodies to carbohydrates in the cell wall (anti -M antibodies) of group A Streptococcus cross-react with proteins in cardiac valves. Time f rom acute streptococcal infection to onset of symptomatic rheumatic fever (RF) is usually 3 \200\2234 weeks. RF is thought to complicate up to 3% of untreated streptococcal sore thro ats. Previous episodes of RF predispose to recurrences. Other areas of cross-reactivity may explain noncardiac \201 ndings (e.g., involvement of connective tissue in joints causing arthritis, caudate nucleus in brain leading to Sydenham \200\231s chorea). RF commonly cau ses a Pericarditis constriction. may cause acute heart failure and arrhythmias. Myocarditis affects the mitral valve (65% \200\22370%), aortic valve (25%), and Endocarditis tricuspid valve (10%, never in isolation), causing acute regurgitation and heart failure but chronic stenosis. Pericardium, perivascular regions of myocardium, and endocardium develop foci of eosinophilic collagen surrounded by lymphocytes, plasma cells, and macrophages called Asch off bodies. \200 \200 pancarditis. rarely causes hemodynamic instability/tamponade or \200 Clinical features \200 \200 \200 Sore throat Fever, abdominal pain, and epistaxis. Migratory large-joint of cases. Duration is <4 weeks at each site. There is severe pain and tenderness in contrast to a mild degree of joint swelling. occurs 1 \200\2235 weeks prior in two-thirds of cases. polyarthritis starting in the lower limbs in 75% ACUTE RHEUMATIC FEVER 177 Pancarditis mitral and aortic regurgitation, and pericarditis. Chorea pharyngitis. Patients exhibit dif \201 culties in writing and speaking, generalized weakness, choreiform moveme nts, and emotional lability. Joints are hyperextended with hypotonia, diminished tendon re \202 exes, tongue fasciculation, and a relapsing grip (alternate increases and decreases i n tension). Full recovery is usually in 2 \200\2233 months. Erythema marginatum and central clearings on the trunk and proximal limbs. It is seen in 5% \200\22313% of cases. It begin s as erythematous, nonpruritic papules or macules that spread outward. It fades and reappea rs in hours and persists throughout the disease course. See Fig. 4.2. Subcutaneous nodules after the onset of pancarditis. They occur mainly over bony surfaces or joint prominences a nd tendons and usually last 1 \200\2232 weeks. There is a risk of overdiagnosing RF in chil dren admitted with fever, soft murmurs, and arthralgia, all of which are common in childhoo d. Evidence for an antecedent streptococcal infection is required for the de \201 nitive d iagnosis \200\224see Box 4.1. occurs in 50% of cases with features of acute heart failure, occurs in 10% \200\22330%, usually occurs 1 \200\2236 months after is an evanescent rash with serpiginous outlines are seen in 0 \200\2238% of cases usually several weeks Treatment \200 Oral penicillin V for 10 days or intramuscular penicillin G (single dose of 1.2 million uni ts) to treat the acute infection. If patient is penicillin allergic, use oral erythromycin, azithromycin, or cephalexin for 10 days. Oral aspirin 4 \200\2238 g daily until ESR and CR P are normal Systemic corticosteroids for 2 \200\2234 weeks for moderate \200\223severe car ditis Standard medical therapy (i.e., diuretics, ACE inhibitors, and digoxin) for heart fai lure \200 \200 Figure 4.2 Erythema marginatum in rheumatic fever. CHAPTER 4 Valvular heart disease 178 Box 4.1 Diagnostic criteria for rheumatic fever (Jones criteria) \200 \200 Evidence of group A streptococcal pharyngitis Either a positive throat culture or rapid str eptococcal antigen test, or an elevated or rising streptococcal antibody titer (samples tak en 2 weeks apart). Plus two major or one major and two minor Jones criteria: Minor criteria \200 \200 \200 \200 Major criteria \200 Polyarthritis \200 Carditis \200 Chorea \200 Erythema marginatu m \200 Subcutaneous nodules Fever Arthralgia Prolonged PR interval Elevated ESR and CRP Prognosis \200 \200 \200 \200 Determined by severity of cardiac involvement. Acute-phase duration is about 3 months in 80 % of cases. Mortality is 1% \200\22310% in developing countries. Recurrence rates are high and are most common in the \201 rst 2 years following acute infection. Chronic valve dise ase occurs in one-third without and two-thirds with recurrent infections. Murmurs resolve i n 50% of cases up to 5 years after index infection. Antibiotic prophylaxis against group A streptococcal infection is used to prevent recurrence of RF. It is usually continued for at least 10 years or until young adulthood. Daily oral penicillin or intramuscularly penicill in injection every 3 \200\2234 weeks are standard regimens. Erythromycin can be used in pen icillin-allergic patients. \200 World Health Organization 2001 guidelines for prophylaxis \200 Patients without proven carditis: at least 5 years of antibiotic prophylaxis following diag nosis of acute RF or until age 18. Patients with mild mitral regurgitation: at least 10 yea rs of prophylaxis or until age 25. Patients with severe valve disease and/or after valve su rgery: lifelong prophylaxis. MITRAL STENOSIS 179 Mitral stenosis The most common etiology is rheumatic heart disease. Other causes are rare and include the following: \200 Congenital (isolated lesion or in association with an atrial septal defect [ASD] \200\224Lu tembacher \200\231s syndrome, or other left-sided obstructive lesions (Shone complex) Carci noid syndrome (stenosis usually not severe and associated with regurgitation) Fen-phen valv ulopathy (stenosis usually not severe and associated with regurgitation) Mucopolysaccharido ses (e.g., Hurler \200\231s syndrome) Endocardial \201 broelastosis Radiation Mitral annu lar calci \201 cation (doesn \200\231t usually cause severe stenosis) Iatrogenic following mitral valve repair for mitral regurgitation (MR) Prosthetic mitral valve obstruction \200 \200 \200 \200 \200 Stenosis occurs at three levels: chordae (fuse, thicken, and shorten), cusps (thicken and c alcify), and commissures (fuse with the valve cusps still mobile). Left atrial myxoma and c or triatrium can cause similar patho- physiology by obstructing left ventricular (LV) in \202 ow. Pathophysiology Elevated left atrium (LA) pressure is required to drive blood through the n arrowed mitral valve ori \201 ce during diastole, leading to pulmonary venous hypertension and exertional dyspnea. Secondary pulmonary arterial hyper- tension leads to right ventric ular (RV) hypertrophy and failure. LV systolic function is preserved but as \201 lling is impaired, adequate car- diac outpu t (CO) cannot always be maintained, especially with exercise and tachycardia. Onset of atri al \201 brillation (AF) is associated with abrupt clinical deterioration due to both the loss of atrial systole and the fast heart rate, which shortens the diastolic \201 lling p eriod. Clinical features \200 \200 Dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea. Acute pulmonary edema may be precipitated by uncontrolled AF, exercise, pulmonary infection, anesthesia, and pregnancy. AF increases the risk of thromboembolism. Systemic embolism occurs in 20% \200\22330% and u sually originates in the dilated LA and LA appendage. Fatigue is due to reduced cardiac out put reserve. Hemoptysis can occur for a variety of reasons: alveolar capillary rupture (pin k frothy pulmonary edema); bronchial vein rupture (larger hemorrhage); blood-stained sputum of chronic bronchitis; pulmonary infarction (low CO, immobile patient). Chest pain similar to angina may occur in patients with pulmonary hypertension and RV hypertrophy, even with normal coronaries. The enlarging LA may compress surrounding structures, producing hoarse v oice (left recurrent laryngeal nerve compression \200\224Ortner \200\231s syndrome), dyspha gia (esophageal compression), and left lung collapse (left main bronchus compression). \200 CHAPTER 4 Valvular heart disease 180 Physical exam \201 ndings (see Fig. 4.3) \200 \200 \200 \200 \200 \200 \200 Mitral facies or malar \202 ush Prominent a-waves in jugular venous pressure (JVP) if in sinus rhythm Small-volume arterial pulse Irregularly irregular pulse in AF \200\234Tapping \200\235 apex beat \200\224palpable S1 Diastolic thrill at apex Left parasternal heave (du e to RVH), palpable pulmonic closure Auscultation S1 is loud if in sinus rhythm and the valve is pliable (Fig. 4.4). P2 is accen - tuated. Opening snap (OS) of the MV is heard best at or medial to the apex in expiration. The A2 \200\223OS interval varies inversely with severity of stenosis. Low-pitched, rumbling, mid-diastolic murmur with presystolic accentu- ation (if in sinus rh ythm) is heard best at the apex with patient in left lateral position. Early diastolic murm ur due to pulmonary regurgitation from pul- monary hypertension (Graham \200\223Steell murm ur) may be heard. Mitral facies and central cyanosis with developing pulmonary hypertension Low volume irregu lar pulse? All pulses present (emboli) Face \200\234V \200\235 wave in JVP 2 TR: pronounced systolic wave Pulmonary regurgitation (Graham Steell) Inspiration Loud P2 (may be palpable Pulmonary hypertension TR. Pan SM RV \200\234heave \200\235 Apex beat. \200\234Tapping \200\235 if valve mobile dut to palpable mitral valve closure ( S1). Not displaced Pulsatile liver Mobile leaflets Rigid valve AF SR No opening snap OS A2 A2 Loud S1 Soft S1 Pansystolic additional MR Loud S1 Opening snap Mitral diastolic murmur Rumbling No S3 unless dominant regurgitation axilla Pre-systolic accentuation (Atrial systole) Figure 4.3 Physical signs in mitral stenosis. Reproduced with permission from Swanton RH. C ardiology Pocket Consultant, 5th ed. Copyright Wiley-Blackwell 2003. MITRAL STENOSIS 181 (a) (b) Tricuspid diastolic flow murmur 1 A2 A2 P2 (Fixed) 1 OS Pulmonary systolic flow murmur Figure 4.4 Similarity on auscultation between (a) mixed mitral valve disease and (b) ASD. R eproduced with permission from Swanton RH. Cardiology Pocket Consultant, 5th ed. Copyright Wiley-Blackwell 2003. Table 4.1 Radiographic features of mitral stenosis PA \201 lm \200 \200 \200 \200 \200 \200 Lateral \201 lm \200 \200 \200 \200 LA or RV enlargement Valvular calci \201 cation McCallum \200\231s patch (LA calci \201 c ation) Esophageal indentation on barium swallow Straight or convex L heart border Double shadow of LA behind RA Splaying of carina (>90) Di lated upper lobe veins Prominent pulmonary conus Pulmonary hemosiderosis Testing \200 ECG shows LA abnormality (P mitrale) if in sinus rhythm. AF is common. Right axis deviation and RV hypertrophy. RA abnormality (P pulmonale) occurs with severe pulmona ry hypertension/cor pulmonale. CXR lobe veins, pulmonary artery enlargement, Kerley B lines \200\224interstitial edema. Large left atrium is visible as a double shadow (Table 4.1). T TE is the diagnostic modality of choice. Parasternal long-axis (PLAX) view shows enlarged l eft atrium and doming of the valve lea \202 ets due to commissural fusion. In parasternal short-axis (PSAX) view, mitral valve ori \201 ce can be measured by planimetry. Valvular a nd subvalvular thickening and calci \201 cation can be seen. M-mode shows restricted valve lea \202 et separation due to commissural fusion. Continuous-wave (CW) Doppler can be use d to measure transvalvular pressure gradient and valve area, as well as estimate pulmonary artery pressure from TR jet. It is important to evaluate for coexistent MR or other valvula r disease. Stress ECHO provides better anatomic detail and can visualize thrombi in TEE the LA and LA appendage, which is especially important prior to percutaneous mitral balloon va lvotomy (PMBV). Cardiac catheterization: gradient. If the mean mitral gradient is low at re st, repeat measurements following exercise in cath lab (e.g., straight-leg raising or lifti ng bags of saline). Assess for coexisting coronary and valvular lesions. shows straightening of the left heart border, prominent upper \200 to assess for exertional pulmonary hypertension increased PCWP to LV end diastolic pressure CHAPTER 4 Valvular heart disease 182 Treatment Medical \200 Asymptomatic patients \200\224observe clinically for development of AF, pulmonary hypertens ion, or symptoms. Mild symptoms \200\224salt intake restriction and oral diuretics as neede d B-blocker, nondihydropyridine calcium channel Atrial \201 brillation \200\224 blocker, or digoxin for rate control. Restoration of sinus rhythm may be attempted if appropriate. A nticoagulants \200\224at least 1 year for those with thromboembolism and lifelong if in AF. Patients with low-output states and R heart failure should also be anticoagulated. There i s no proven bene \201 t if the patient is in sinus rhythm. Antibiotic prophylaxis for mitr al stenosis is no longer indicated. \200 Percutaneous mitral balloon valvotomy (PMBV) Moderate to severe symptoms or development of pulmonary hyperten- sion (>50 mmHg at rest or >60 mmHg with exercise) warrants mechanical r elief of mitral valve obstruction, and PMBV is the preferred approach to achieve this. In P MBV, a guide wire is placed in LA after trans-septal puncture and a balloon (Inoue balloon) is directed across the valve and in \202 ated at the ori \201 ce. This procedure is suitable for patients with pliable valves with mini- mal MR, no subvalvul ar distortion, and without heavy calci \201 cation. An ECHO-derived Wilkins score <8 predi cts procedural success and should be determined in each case. Surgical (see Box 4.2) \200 Closed valvotomy through LV apex. Results are inferior to PMB V so it is now rarely performed. Open valvotomy valvotomy. Cusps are separated under direct vision. Any fusion of subvalvular apparatus is loosened. Mitral valve replacement severely diseased or heavily calci \201 ed. . Fused cusps separated by a dilator introduced with cardiopulmonary bypass is preferred to closed is used if there is signi \201 cant MR or the valve is Box 4.2 ACC/AHA 2006 guidelines* for surgery in mitral stenosis \200 Class I: Symptomatic (NYHA Class III/IV) patients with moderate to severe MS when PMBV is n ot available or is contraindicated (i.e., LA thrombus, signi \201 cant mitral regurgitatio n) Class IIA: pulmonary hypertension not candidates for PMBV Class IIB: Class III: be perfo rmed in patients undergoing surgery for MS. Patients with NYHA Class I \200\223II symptoms and severe \200 Recurrent systemic emboli despite anticoagulation Patients with mild MS. Closed comissuroto my should not Bonow, RO, et al. (2006). ACC/AHA 2006 guidelines for the management of patients with valvu lar heart disease. J Am Coll Cardiol 48:598 \200\223675. MITRAL REGURGITATION 183 Mitral regurgitation Causes Acute \200 \200 Infective endocarditis Acute myocardial infarction (MI) (usually inferior wall) from papill ary muscle dysfunction or acute rupture Trauma Chronic \200 \200 \200 \200 \200 \200 \200 \200 Mitral valve prolapse Rheumatic heart disease Ischemic heart disease Left ventricular dilat ation of any cause Hypertrophic cardiomyopathy Carcinoid syndrome Fen-phen valvulopathy Con genital lesions (i.e., cleft mitral valve). Pathophysiology The LV unloads into the LA during systole. In acute MR, the LA size is usu- ally normal initially because of normal compliance, and this results in raised LA pressure and acute pulmonary edema. In longstanding severe MR, the LA enlarges, which accommodates the volume overload with minimal rise in LA pressure. In this case, symptoms usually occur with exertion or tachycardia, which causes further increases in LA pressure. Symptoms \200 \200 In acute severe MR, pulmonary edema is common. In chronic MR, fatigue (due to impaired forw ard CO), exertional dyspnea, orthopnea, and systemic embolization (less common than in MS) occur. Palpitations are due to premature atrial beats or AF. Symptoms of pulmonary hyperten sion/RV failure occur in later stages. Physical examination \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Rapid upstroke in arterial pulse Prominent a-waves in JVP in patients in sinus rhythm Large v-waves if associated tricuspid regurgitation (TR) Forceful apex displaced laterally Pansy stolic murmur loudest at the apex and radiating into the axilla Systolic thrill at apex Sof t \201 rst heart sound Wide splitting of S2 due to premature aortic valve closure Promine nt low-pitched S3 A mid-diastolic \202 ow murmur may follow S3. Mid-systolic click in mit ral valve prolapse (MVP) CHAPTER 4 Valvular heart disease 184 Testing \200 ECG shows features of LA enlargement, left ventricular hypertrophy (LVH), an d RA enlargement in pulmonary hypertension. AF is common in chronic MR. CXR venous congesti on, and calci \201 ed mitral annulus may be seen. is the diagnostic test of choice. Dilate d LA, hyperdynamic LV TTE (until late when LV failure occurs) can be found, as can features of MVP, ischemic MR (i.e., lea \202 et tethering). Color Doppler is used to detect and qu antify the MR, including jet direction. Assess LV size and function (EF, end systolic diame ter, end diastolic diameter). CW Doppler is used to assess velocity of the regurgitant jet and estimate PA pressure from the TR jet. Assess for presence of vegetations in infective e ndocarditis as well as associated valve disease (i.e., TR). TEE shows the anatomy in greate r detail and allows accurate assessment of the feasibility of valve repair. It has higher s ensitivity for detecting vegetations in infective endocarditis. It should be performed prio r to surgery. Cardiac catheterization v-waves are on PCWP tracing. Contrast left ventriculo graphy can quantify MR as 1+ (mild) to 4+ (severe) based on the degree of LA opaci \201 ca tion. Coronary angiography is used to assess for obstructive CAD prior to MV surgery. shows cardiomegaly. There is LA and LV enlargement. Pulmonary con \201 rms the severity of the lesion. Elevated Prognosis Outcome is poor in severe symptomatic mitral regurgitation, with a 33% survival a t 8 years without surgical intervention. Death is usually due to heart failure or is arrhyt hmia related (i.e., sudden cardiac death, stroke). Management Medical management Infective endocarditis prophylaxis is no longer required acco rding to the 2007 ACC/AHA guidelines. Asymptomatic patients with severe MR can be managed c onservatively with serial echocardiograms (every 6 \200\22312 months) to assess for LV dysf unction (dilation, drop in EF) and pulmonary hyper- tension, as well as adequate clinical f ollow-up to evaluate for the onset of symptoms or AF. There is no bene \201 cial role for vasodilator therapy in asymptomatic patients with chro nic MR. Vasodilators may be used acutely in symptomatic patients to increase forward CO and reduce regurgitant volume. Patients with congestive heart failure (CHF) should also receive diuret- ics for symptom re lief, though outcome without surgery is poor. Chronic medical therapy with vasodilators and diuretics is only recommended in patients who are not surgical candidates. In atrial \201 brillation, B-blockers and/or calcium channel blockers or dig- oxin should be given for rate control, and these patients should receive anticoagulation, unless contr aindicated. Rhythm control in AF should be attempted in those patients who remain symptomat ic despite adequate attempts at rate control. MITRAL REGURGITATION 185 Surgical treatment Surgery is indicated in patients with severe MR who are symptomatic (Box 4.3). Asymptomatic patients with severe MR may need surgery if there is LV enlargement or LV systolic dysfunction. Pulmonary hyperten- sion and new-onset AF are other indications fo r surgery. Timing of the surgery is very important. Reduction of the left ventricular ejection fractio n (LVEF) <60% or end systolic dimension (ESD) of >45 mm indicates LV systolic dysfunction a nd the need for surgery. \200 Mitral valve repair is preferred to valve replacement if technically feasible. Long-term an ticoagulation and risk of hemorrhage and thromboembolism can be avoided. Mitral valve repla cement with a prosthesis, either mechanical or bioprosthetic, is needed if valve lea \202 ets are severely damaged or heavily calci \201 ed. Box 4.3 2006 ACC/AHA guidelines* for surgery in MR Class I \200 \200 Symptomatic severe acute MR Severe symptomatic chronic MR in the absence of severe LV dysfu nction (LVEF <30% or ESD >55 mm) Asymptomatic severe chronic MR with LVEF of 30% \200\22360 % and/or ESD \211 40 mm Mitral valve repair is preferred to replacement in most patients. Class IIa \200 Mitral valve repair in asymptomatic severe chronic MR with preserved LV function (LVEF >60% and ESD <40 mm) if likelihood of successful repair \211 90% Asymptomatic severe chronic M R and preserved LVEF with new- onset AF or pulmonary hypertension (PASP >50 mmHg at rest or >60 mmHg with exercise) If mitral valve repair is highly likely, severe symptomatic chroni c MR due to a primary abnormality in the mitral valve apparatus and severe left ventricular dysfunction (LVEF <30% or ESD >55 mm) Class IIb \200 Mitral valve repair for severe MR due to severe LV dysfunction (LVEF <30%) in patients with persistent symptoms despite optimal medical therapy for heart failure Class III \200 \200 Isolated valve surgery for mild to moderate MR Asymptomatic patients with preserved LV func tion if MV repair not feasible Bonow RO, et al. (2006) ACC/AHA 2006 guidelines for the management of patients with valvula r heart disease. J Am Coll Cardiol 48:598 \200\223675. CHAPTER 4 Valvular heart disease 186 Mitral valve prolapse (Barlow \200\231s syndrome, \202 oppy mitral valve syndrome) Causes Primary or classic mitral valve prolapse (MVP) is an idiopathic valvular abnormality characterized by myxomatous degeneration of the mitral valve lea \202 ets and subvalvular apparatus in the absence of any recognizable systemic connective tissue disorder. It can b e inherited as an autosomal dominant phenotype with incomplete penetrance. Secondary MVP occurs in the setting of known connective tissue dis- orders, including Marfa n \200\231s syndrome, Ehlers \200\223Danlos syndrome, pseudox- anthoma elasticum, and osteo genesis imperfecta. MVP is also frequently associated with atrial septal defects and Ebstei n \200\231s anomaly. One can also see acquired lea \202 et prolapse (i.e., functional MVP) in ischemic heart dis- ease and dilated cardiomyopathy. Overall prevalence is approximatel y 2% and is similar in men and women. Pathophysiology Myxomatous degeneration and excess mucopolysaccharide accumulation lead to large, \200\234 \202 oppy \200\235 valve lea \202 ets. Prolapse can be caused by papilla ry muscle dysfunction, elongated or ruptured chordae tendinae, a dilated mitral annulus, an d/or redundant lea \202 ets. MV lea \202 et (usually posterior) prolapses into the LA dur ing ventricular systole. Mitral regurgitation results from lea \202 et malcoaptation; this is the most common cause of MR in adults. Symptoms Most patients are asymptomatic, though some have a constellation of nonspeci \201 c symptoms such as atypical chest pain, palpitations, and panic attacks. These symptoms ar e probably related to autonomic dysfunction rather than the mitral valve abnormality. Patients may also develop symptoms of MR if it becomes signi \201 cant, which occurs in roughly 7% patients with classic MVP. Examination Mid-systolic click is due to tensing of the chordae tendinae and the pro- lapse d lea \202 et. The click may occur closer to S1 with maneuvers that decrease LV volume, su ch as standing from a squatting position. A mid-late systolic murmur may be heard if there is associated MR. Testing TTE is the most useful noninvasive test to establish the diagnosis and assess for t he presence and severity of MR. Classic MVP is de \201 ned as systolic displacement of one or both MV leaf- lets by (cid:1 16)2 mm into the LA beyond the high points of mitral annulus in the PLAX view and lea \202 et thickness (cid:116)5 mm. Lea \202 et thickness <5 mm is referred to as nonclassic MVP. MITRAL VALVE PROLAPSE 187 Treatment Infective endocarditis prophylaxis is no longer recommended. B-Blockers can provi de symptomatic relief from atypical chest pain and palpitations. Rate or rhythm control and anticoagulation are needed in patients with AF. MV repair (rarely replacement) is indicated for severe MR if sympto- matic or for LV dysfunction. Prognosis This condition is benign in most patients and determined largely by the severity of MR; moderate to severe MR is the most important predictor of adverse outcomes. Complicat ions of MVP occur in 1% patients per year and include signi \201 cant MR, infective endoca rditis, cerebrovascular events, and arrhythmias. Although a variety of arrhythmias may occur in patients with MVP, the incidence of sudden c ardiac death is quite low (1.9 per 10,000 per year) in the absence of hemodynamically signi \201 cant MR. CHAPTER 4 Valvular heart disease 188 Aortic stenosis Incidence Aortic stenosis (AS) is the most common acquired valvular lesion in adults. Incidence is increasing as the population ages and with improvements in diagnost ic modalities, primarily Doppler echocardiography. Symptoms and prognosis are related to the degree of left ventricular out \202 ow tract (LVOT) obstruction. Differential diagnosis of LVOT obstruction \200 \200 Valvular stenosis Supravalvular stenosis commonly associated with William \200\231s syndrom e. Subvalvular stenosis narrowing. Dynamic obstruction can occur in hypertrophic obstructiv e cardiomyopathy (HOCM). : calci \201 c AS is the most common etiology. : tubular narrowing of proximal ascending aorta is : discrete membrane or a tubular muscular Causes of valvular AS Acquired Calci \201 c AS Calci \201 c AS (senile degenerative) is m ost common, affecting 2% of peo- ple >65 years old, with an increasing incidence with age. End-stage renal disease and Paget \200\231s disease of bone are also associated with valvul ar calci \201 cation. Risk factors for atherosclerosis, such as diabetes, hypertension, hyperli- pidemia, and smo king, play a role in the underlying in \202 ammatory process. This leads to heavy lea \202 et calci \201 cation, thickening, and immobility with reduced systolic opening. Aortic sclerosis without LVOT obstruction is common and occurs in 25% patients >65 years of age and may precede stenosis, with 9% of patients developing stenosis in 5 years. Rheumatic AS This usually occurs in conjunction with mitral valve disease. Commissural fusi on and retraction of valve lea \202 ets leads to systolic doming and impaired lea \202 et coaptation. One often sees associated aortic regurgitation. Congenital Bicuspid aortic valve This is seen in 2% of the population. There is often famil ial clustering and autosomal dominant inheritance with incomplete penetrance. This condition results in chronic turbulent \202 ow, which leads to accel- erated lea \202 et calci \201 cation and \201 brosis. It usually presents clinically with signi \201 cant stenosis at ages 45 \200\22365 years. It is often associated with aortic patholog y (aneurysm, dissection, or coarctation), so all patients should be screened for aortic inv olvement at time of diagnosis. Unicuspid aortic valve This presents in infancy. AORTIC STENOSIS 189 Pathophysiology Progressive valvular narrowing and obstruction to left ventricular out \202 ow lead to pressure overload and compensatory concentric hypertrophy to lessen the inc reased wall stress. Diastolic dysfunction and decreased ven- tricular compliance lead to el evated LV diastolic pressure, which reduces the coronary perfusion gradient, resulting in i schemia. Ischemia can also result from increased myocardial O2 consumption due to increased LV mass and prolonged systolic ejection time. When valve obstruction becomes critical, LV systolic failure can occur. Symptoms and presentation \200 \200 There is a long latent asymptomatic period. is due to myocardial ischemia from O2 supply \200\223demand Angina mismatch. Only half of the affected patients have signi \201 cant ep icardial coronary stenosis. Syncope LVOT obstruction/hypotension. Exertional dyspnea/CHF Su dden cardiac death occurs rarely as the initial presentation of symptomatic AS (incidence i s 0.4%/year in asymptomatic patients with severe AS). Exercise treadmill testing may be hel pful if presence of symptoms or functional status is equivocal from the patient \200\231s h istory. is due to arrhythmias, abnormal vasodepressor re \202 exes, and \200 is usually due to diastolic heart failure. Physical exam \200 Small-volume, slow rising pulse (pulsus parvus et tardus) is best felt at the carotid. BP \200\224narrow pulse pressure; in advanced AS systolic BP is decreased. Prominent a-wave on JVP. Sustained apical impulse. Systolic thrill is felt in the aortic area (second intercos tal space on right) during full expiration. Auscultation \200\224S1 normal or soft. S2 norm al in mild AS. As severity of AS worsens, A2 is delayed by prolonged systolic ejection time and S2 may be paradoxically split (P2 before A2), although it is usually soft or absent in severe AS. An S4 (atria contracting into stiff ventricle) and systolic ejection click (if valve pliable, especially bicuspid valves) may also be heard. Systolic ejection murmur is h eard throughout precordium but is best heard in the aortic area in full expiration and usua lly radiates to carotids. The murmur intensity peaks later in systole as AS worsens. The following exam \201 ndings are most speci \201 c for severe AS: \200 \200 \200 Late-peaking systolic murmur Delayed carotid upstroke Soft or absent S2 CHAPTER 4 Valvular heart disease 190 Aortic stenosis: management Diagnostic testing \200 ECG One may see AF. CXR dilatation in the ascending aorta. TTE restricted opening (2D and M -mode); also evaluate for congenital abnormalities and aortic pathology. Assess for LVH and LV systolic and diastolic function. Color Doppler CW Doppler calculate valve area using th e continuity principle. Dobutamine stress ECHO aortic stenosis from pseudoaortic stenosis d ue to low cardiac output. Cardiac catheterization artery disease prior to aortic valve surg ery. There is no need to assess valve gradient (signi \201 cant risk of embolic events wit h this; CW Doppler accurately assesses gradient and LV function) unless there is a discrepa ncy between echocardiogram and clinical \201 ndings. TEE is used for calculation of the v alve area by planimetry if TTE is nondiagnostic and to assess for aortic pathology (especia lly in patients with bicuspid valves). shows LVH with strain; branch bundle block (BBB) (either R or L). shows calci \201 cation involving valve or aortic root, poststenotic is the diagnostic test of choice. It will show a calci \201 ed valve with \200 is used to look for concomitant AR and/or MR. is used to measure transvalvular pressure gradient and can distinguish low-gradient true severe is used to assess for concomitant coronary Severity Severity is classi \201 ed according to pressure gradient and valve area (Table 4 .2). Echocardiography with Doppler is the preferred modality to acquire these measurements. Prognosis AS is a progressive condition that gradually worsens over time. Symptoms are usua lly not present until stenosis is severe. Once symptoms occur, prognosis without surgery is poor: of patients who present with symptoms of angina, 50% will die within 5 years; if pat ients present with syncope, 50% will die in 3 years; if patients present with congestive he art failure, 50% will die within 2 years. Treatment Surgery Aortic valve replacement (AVR) is the mainstay of therapy for sympto- mat ic patients and can be performed with a very low (1%) operative mor- tality (see Box 4.4). Medical therapy Medical therapy offers very little to symptomatic patients in terms of impr oved outcomes. These patients should be referred promptly for sur- gery. Medical therapy (i .e., diuretics) may provide temporary and palliative symptomatic relief to patients who are not surgical candidates, but must be administered with caution to avoid hypovolemia and hy potension. AORTIC STENOSIS: MANAGEMENT 191 Table 4.2 ACC/AHA classi \201 cation* of AS severity Gradient (mmHg) Velocity (m/sec) Valve area (cm2) Severity Mild <25 <3.0 >1.5 Moderate 25 \200\22340 3.0 \200\2234.0 1.0 \200\2231.5 Severe >40 >4.0 <1.0 Bonow, RO, et al. (2006) ACC/AHA 2006 guidelines for the management of patients with valvul ar heart disease. J Am Coll Cardiol 48:598 \200\223675. Box 4.4 2006 ACC/AHA guidelines* for AVR in AS Class I \200 \200 Symptomatic patients with severe AS Patients with severe AS undergoing CABG or aortic or ot her valvular surgery Patients with severe AS and LVEF <50% Class IIa \200 Patients with moderate AS undergoing CABG or aortic or other valvular surgery Class IIb \200 Severe AS in asymptomatic patients who have an abnormal response to exercise such as the de velopment of symptoms or hypotension Severe AS in asymptomatic patients with a high likelih ood of rapid progression Severe AS in asymptomatic patients in whom surgery might be delaye d at the time of symptom onset Mild AS in patients undergoing CABG surgery in whom there is evidence, such as moderate to severe valve calci \201 cation, that progression may be rap id 2, mean gradient Extremely severe AS (aortic valve area <0.6 cm >60 mmHg, and aortic jet velocity >5.0 m/sec) in asymptomatic patients in whom the expected operative mortality is (cid:100)1% Class III \200 For the prevention of sudden cardiac death in asymptomatic patients who have none of the cl ass IIa or IIb \201 ndings Bonow, RO, et al. (2006). ACC/AHA 2006 guidelines for the management of patients with valvu lar heart disease. J Am Coll Cardiol 48:598 \200\223675. CHAPTER 4 Valvular heart disease 192 Use of medications (particularly HMG-CoA reductase inhibitors) to delay AS progression in a symptomatic patients has been studied and the results thus far are inconclusive. Transcatheter techniques Balloon aortic valvuloplasty was introduced as a nonsurgical alter native treatment for AS and is integral to the management of congenital AS in the pediatric population. Results in the adult population are not as good as anticipated because of proc edural complications and high restenosis rates. Aortic valvuloplasty is currently not an acceptable alternative to surgi- cal AVR and its u se should be restricted to palliative therapy in patients deemed nonoperable and as a bridg e to AVR in hemodynamically unstable patients. Percutaneous aortic valve replacement is currently being performed at experienced centers a nd may be a valuable treatment approach in the future. Current use is restricted to patient s who are not surgical candidates. AORTIC REGURGITATION 193 Aortic regurgitation Causes Valvular \200 Rheumatic fever that they cannot appose properly. Infective endocarditis leads to \201 brosis, fusion, and retraction of cusps such causes destruction of valve lea \202 ets. Aortic root disease Dilatation, aneurysm, and dissection cause failure of coaptation of cus ps. One may see diastolic cusp prolapse in dissection. Causes \200 \200 \200 \200 \200 \200 \200 Hypertension Marfan \200\231s syndrome Osteogenesis imperfecta Syphilis Spondyloarthritides (ankylosing spondylitis, Reiter \200\231s, etc.) Trauma Bicuspid aortic valve Incidence Aortic regurgitation (AR) is less common than AS. Valvular causes are becoming le ss frequent and aortic root causes now account for >50% of cases. Pathophysiology As the aortic valve becomes incompetent, more stroke volume regurgi- tates into LV during diastole, causing LV volume overload. Cardiac output is maintained by increa sing stroke volume at the expense of increased LV end-diastolic volume. Eventually, with fu rther LV dilatation, myocyte func- tion deteriorates and LV failure occurs. Symptoms Symptoms include dyspnea/CHF, angina, and symptoms of an underlying cause (i.e., c hest pain in aortic dissection, fever in infective endocarditis).