Chronic rheumatic heart disease, representing the permanent lesions of the cardiac valves, is the most serious consequence of rheumatic fever. It accounts for a significant number of repeated hospitalisations and deaths. Recurrences of rheumatic fever play an important role in the worsening of the valvar lesions, but the damage, as a result of the process of cicatrisation, can be progressive even in the absence of subsequent acute episodes. The clinical presentation, the mortality, as well as the frequency and speed of development of an established valvar disease after the acute phase, vary considerably geographically, influenced primarily by the socioeconomic and medical backgrounds of the populations involved. In developed countries, severe rheumatic valvar disease is now uncommon in children and adolescents, and treatment for the advanced form of the disease is usually limited to adults. In contrast, in many developing countries, chronic rheumatic heart disease remains the most important cause of acquired cardiac disease among patients aged between 5 and 30. 1 On a global scale, it has been estimated that around 2 to 4 million patients aged from 5 to 14 are affected with rheumatic heart disease. It is also anticipated that each year an additional 282,000 new patients present with the ravages of chronic disease. 2 The prevalence of chronic disease was mostly based on surveys of schoolchildren, with rates ranging from 0.2 to 77.8 for each 1000 of the population in developing communities. 3–7 The highest rates are registered in the Pacific region and in the Republic of Congo. 8 Among 550 Brazilian students, aged from 10 to 20 years and chosen randomly, the prevalence was calculated at 1.8 cases for each 1000 students. 9 Although progress in diagnosis and management over recent decades has provided a better quality of life, the disease causes significant disabilities and premature deaths in young individuals, with considerable personal and collective costs. The disability-adjusted life years lost to chronic rheumatic heart disease ranged from 27.4 to 173.4 per 100,000 population, giving an estimated 6.6 million life years lost each year throughout the world. The disease is responsible for up to two-thirds of the admissions to hospital due to cardiac problems in some countries. The rates of death because of chronic rheumatic heart disease show a wide variation, from 0.5 to 8.2 for each 100,000 population, according to the area of investigation. For the year 2000, the number of deaths worldwide was estimated at 332,000. 4
The healing process of rheumatic carditis results in varying degrees of fibrosis and valvar damage. In some instances, fusion and thickening of the pericardium may also occur, but this rarely affects the ultimate cardiac performance. Resolution of the chronic valvar disease has been associated with the degree of the valvar involvement during the acute inflammatory process. Those suffering only mild valvar lesions in the acute phase, with minor degrees of thickening of the valves and tendinous cords, and some fibrosis of the valvar endocardium, are unlikely to suffer abnormal haemodynamic effects in the chronic phase. If recurrences are prevented, mitral insufficiency in patients without cardiomegaly, pericarditis, or cardiac failure is expected to heal without scarring in about four-fifths of cases. 10 On the other hand, more severe valvar damage can occur in the initial acute episode, and the early onset of significant lesions has an important impact on the development and severity of the permanent valvar damage. Considering the clinical and echocardiographic evaluation of cardiac involvement from the acute to the chronic phase, regression of valvar lesions was found mostly in those initially suffering mild carditis, with less regression in those known to have had moderate carditis, and no improvement observed in cases of severe carditis. 11 Poor outcomes for rheumatic heart disease have also shown a causal relation with recurrences. 12–17 Repeated episodes of rheumatic fever usually lead to significant valvar disease in childhood and adolescence, often associated with pulmonary hypertension. The socioeconomic condition is known to be a contributing factor for the high rates of rheumatic fever, recurrences, and rheumatic heart disease. 8,18 In this setting, a low level of maternal schooling also emerged as a variable interacting with recurrences, as well as featuring as an independent risk factor in predicting severe chronic valvar disease in patients without recurrences. 15 It is also likely that episodes of subclinical carditis can result in chronic rheumatic valvar disease. The fact that many adults present with rheumatic heart disease without an earlier history of an acute episode supports this view, although the exact incidence of subclinical attacks is difficult to evaluate. The true incidence of carditis, nonetheless, is probably much higher than previously thought. Failure to recognise the primary episode of rheumatic fever, and inadequate secondary prevention, were identified as the major contributors to the increase in the frequency of recurrences and chronic rheumatic heart disease. 19 More recent studies using echocardiography have consistently documented that subclinical carditis does occur, and have shown a wide variation in prevalence. 20 Similarly, pathological valvar regurgitation detected only by Doppler echocardiography has been reported during the chronic phase in patients not previously suspected to have rheumatic valvar disease after physical examination. 7,15,21,22 Patients with chronic subclinical rheumatic valvar disease, as well as those with subclinical valvitis, are susceptible to infective endocarditis, which, should it occur, significantly alters the cardiac state.
In all age groups, the mitral valve is most commonly affected, followed by a combination of mitral and aortic valves, then isolated aortic valvar disease, usually incompetence, and combined mitral, aortic, and tricuspid disease. 23–26 Chronic rheumatic involvement of the pulmonary valve is rare. Analysis of the patients seen in the Rheumatic Fever Outpatients Clinic in Belo Horizonte, Brazil, has revealed isolated mitral regurgitation in almost half of the patients with chronic disease, and the combination of mitral and aortic regurgitation as the second most frequent lesion. Valvar insufficiency was present in almost three-quarters, insufficiency and obstruction in just over one-quarter, and isolated valvar obstruction in only 0.7% ( Fig. 54B-1 ).
Mitral insufficiency is the most frequent valvar lesion involved in paediatric surgical series. In developing countries, mitral stenosis is also a common lesion, and percutaneous balloon valvoplasty, or closed mitral commissurotomy, are procedures frequently carried out in children and adolescents in these regions. Mitral or aortic regurgitation may be sufficiently severe to cause life-threatening haemodynamic effects. These complications may require major cardiac surgery, either electively, or even occasionally as an emergency. 27 The progress in diagnostic methods, catheter interventions, surgical expertise and techniques, and the development of improved valvar prostheses has encouraged the increased use of non-surgical and surgical techniques for the treatment of rheumatic valvar disease in children, adolescents and young adults.
PATHOGENESIS OF CHRONIC LESIONS
Recurrent attacks of acute rheumatic fever lead to rheumatic heart disease, characterised by sequels in the cardiac valves and myocardium. Rheumatic heart disease is estimated to occur in around three-fifths of all patients having acute rheumatic fever. The chronic lesions are the consequence of valvar scarring, and of healing of the pancarditis, including fibrosis of the myocardium and occasionally adhesive pericarditis. In the valves, the organisation of superficial fibrin vegetations from the acute phase results in thickening of the leaflets, fusion of the ends of the zones of apposition, and shortening of tendinous cords. Subsequent damage occurs due to local disturbances of haemodynamics and flow of blood leading to deposition and organisation of thrombus. Once neovascularisation of the valvar leaflets has occurred, inflammatory cells can reach the valvar stroma, not only through the endocardial surface, but also from the endothelium of the newly formed vessels. The predominance of cells producing the regulatory interleukins 4 and 10 in the myocardium, as compared to the valvar tissue, explains at least in part the milder or absent inflammation in the myocardium during the chronic phase of the disease, whereas in valvar tissue inflammation is a permanent finding. 28
Myocardial remodelling secondary to pressure or volume overload due to valvar dysfunction depends on the severity and duration of the haemodynamic disturbance. If the valvar lesions stand for long periods, as is likely to occur in patients from countries with limited resources for public health, progressive cardiac hypertrophy, chamber dilation, and interstitial myocardial fibrosis may occur, leading to severe cardiac failure that can become irreversible even after later valvar replacement or valvoplasty. In this context, cardiac transplantation is an option to treat these end-stage patients. In a multi-centric study in Brazil, chronic valvar rheumatic heart disease accounted for 3.5% of all cardiac transplants performed over a period of 16 years. 29
Lesions of the left-sided valves also lead to chronic pulmonary congestion and passive pulmonary hypertension, and consequently to right ventricular hypertrophy and functional tricuspid regurgitation. Atrial fibrillation, a complication present in about half of patients with chronic mitral stenosis as seen in adults, is attributed to the increase of left atrial volume. 30 The disturbed flow of blood in this condition may lead to formation of mural thrombus, and to the risk of systemic thromboembolism. Myocardial dysfunction definitely influences the severity, clinical progress, and prognosis of rheumatic valvar disease.
The potential risk for infective endocarditis in patients with chronic rheumatic disease derives from disruption by the irregular valvar endocardial surface of the normal pattern of laminar flow across the valvar orifice. As stated previously, this progresses to deposition of fibrin. Initially these deposits are sterile and may heal. In the face of significant bacteremia, the microorganisms become enmeshed within the vegetations, leading to infectious endocarditis.
Morphology of Chronic Lesions
The evolution from the initial attack of acute fever to appearance of severe chronic lesions requiring surgical intervention is known to have geographical variation, being shorter in patients from countries with conditions of poor health care because of the greater risk of repeated acute episodes. Although fibrin vegetations and inflammation usually heal, leading to fibrosis of the leaflet, additional damage may be caused by organisation of minute thrombuses deposited on the valvar surface, and also by local haemodynamic disturbances. Moreover, inflammation persists in valvar tissues, perpetuating the process. As discussed already, the mitral valve alone is involved in most children and adults with chronic rheumatic heart disease, but both the mitral and aortic valves are involved in about one-quarter of individuals. 31 Milder lesions can afflict the tricuspid valve, but are rarely seen in the pulmonary valve.
Chronic Rheumatic Mitral Valvar Disease
In the adult patient, isolated mitral stenosis, or stenosis in association with regurgitation, is the most frequent valvar sequel. As with the acute lesions, stenosis is not usually the first presentation of mitral dysfunction, with regurgitation usually seen first. In gross terms, the leaflets are diffusely thickened, and at the early stage of regurgitation, the mural leaflet is retracted, typically showing only one scallop instead of the usual three ( Fig. 54B-2 ). With progression of the disease, the two ends of the zone of apposition between the leaflets fuse together, producing so-called commissural fusion. Varying degrees of shortening and fusion of the cords is also observed, leading, in the most severe cases, to obliteration of the interchordal spaces. In the normal valve, of course, these spaces are wide, and may be considered as part of the valvar orifice ( Fig. 54B-3 ). The morphological feature of obliteration of the intercordal spaces further aggravates the stenosis, and must be given attention during any attempted surgical repair. In severe cases, the valvar apparatus is funnel-like, with the leaflets seemingly inserted directly to the tips of the papillary muscles. Should there be a recurrent acute attack, fibrin vegetations will be found on the already distorted leaflets and cords (see Fig. 54A-7 ). Deposition of calcium is a late complication of the chronic involvement, usually appearing in adulthood, but it may be present in children with accelerated evolution of the disease. The deposits are seen as large yellow masses on the atrial surface of the leaflets, but especially at the ends of the zone of apposition ( Fig. 54B-4 ). In the setting of severe stenosis, the valvar orifice appears slit-like, and is likened to a fish-mouth or button-hole ( Fig. 54B-5 ). As emphasised, the subvalvar apparatus is also stenotic. The left atrium is usually greatly enlarged, carrying the possibility of formation of thrombus and atrial fibrillation. Thrombuses may be attached to the valve itself ( Fig. 54B-6 ), or be formed inside the tubular left atrial appendage. Rarely, a large free-floating ball thrombus may be found inside the left atrium, with the risk of a fatal systemic embolisation or occlusion of the valvar orifice.
Infective endocarditis is a potential complication of valves afflicted by chronic rheumatic lesions ( Fig. 54B-7 ) because of the disturbed pattern of flow of blood and also the irregular endocardial surface. While large vegetations may be misdiagnosed echocardiographically as thrombuses, small ones may be missed, and the diagnosis confirmed only at histological examination.
The differential diagnosis of rheumatic mitral fibrous scarring includes valvar lesions produced by systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, post-thoracic irradiation, and carcinoid valvar disease, and those associated with the use of certain appetite suppressants, such as fenfluramine or phentermine. The clinical history and laboratorial findings, nonetheless, usually point to the proper diagnosis. 31
Chronic Rheumatic Aortic Valvar Disease
As we have discussed, the aortic valve is the second most commonly involved valve, usually in association with involvement of the mitral valve. Isolated aortic lesions are uncommon. In one recent study, 32 solitary involvement of the aortic valve was found in less than 3% of the cases. Rheumatic aortic stenosis is particularly rare in children and adolescents. When seen as an isolated lesion in patients of this age, it is considered to be associated with a congenital lesion. 33
Macroscopically, the leaflets are diffusely thickened and retracted. Fusion along the zones of apposition between the leaflets begins at their peripheral attachments at the level of the sinotubular junction ( Fig. 54B-8 ). As with the mitral valve, calcification is rare in children, but may involve the free edges of the leaflets, which is different from the finding in degenerative aortic stenosis.
Chronic Rheumatic Tricuspid and Pulmonary Valvar Disease
Functional tricuspid valvar regurgitation is a common finding in patients with significant mitral valvar disease, resulting from right ventricular and annular dilation caused by long-standing pulmonary hypertension. When seen, thickening of the leaflets and shortening of cords are the macroscopical features of the chronic lesion, besides focal fusion of the zones of apposition between the leaflets. Calcific deposits are rare. Chronic organic pulmonary valve involvement is very rare. If found, it almost always involves rheumatic lesions in the other three valves. 24 Rheumatic fever, nonetheless, can also be found in patients with congenitally malformed hearts, including tetralogy of Fallot, septal defects, and aortic coarctation, with the chronic lesions then being superimposed on the congenital anomalies. 34,35
HISTOLOGIC FEATURES OF CHRONIC RHEUMATIC VALVAR AND MYOCARDIAL LESIONS
Histologically, valves with chronic rheumatic involvement show dense and diffuse fibrosis, which effaces the typical architecture. It is also possible to recognise newly formed vessels, some with thick walls, along with variable degrees of inflammatory infiltrates made up of lymphocytes and macrophages ( Fig. 54B-9 ). As previously described, the main type of inflammatory cell present is the T lymphocyte of CD4 phenotype, 36 expressing predominantly interferon γ, tumour necrosis factor–α and interleukin 10. Calcium deposits, if seen, are usually surrounded by aggregates of mononuclear cells, including plasma cells. Occasional endocardial ulcerations are covered with thrombus. Aschoff bodies are no longer present at this phase of the disease, unless an acute attack of rheumatic carditis has occurred within the last few weeks. Myocardial fibrous scars result from the organisation of the nodules of the acute phase, and are perivascular in location (see Fig. 54A-8 ). Additional damage is a consequence of altered haemodynamics, and usually involves variable degrees of myocardial hypertrophy.
Secondary Changes in the Airways and Pulmonary Vasculature
Chronic pulmonary congestion due to left valvar and myocardial dysfunction may be so severe as to result in passive pulmonary hypertension. The alveolar septums become thickened, initially by capillary dilation and later by fibrosis, and alveolar lumens may contain numerous haemosiderin-laden macrophages, the so-called heart failure cells. The interlobular septums show oedema and dilated lymphatic vessels. Venous changes may include intimal and adventitial fibrosis, along with hypertrophy of the medial layer. Long-standing congestion results in extension of the lesions to the arterial territory, with medial hypertrophy, intimal fibrosis, and adventitial enlargement of intra- and pre-acinar arteries. 37
VALVAR LESIONS
Mitral Regurgitation
Mitral regurgitation, as an isolated lesion or in combination with other valvar defects, is probably, at all ages, the most common valvar dysfunction resulting from the acute rheumatic process. In developing countries, severe forms have necessitated early surgical intervention in young patients. 38,39 In a recent large series of young patients aged under 18 years, 23 isolated mitral regurgitation, as the single most frequent lesion produced by chronic rheumatic heart disease, was found in one-third of the cohort. Analysis of repair of the mitral valve revealed that over one-quarter of operations were performed in patients aged less than 15 years of age. 24 In South Africa, pure mitral regurgitation was the most common lesion in young patients treated by surgery due to rheumatic mitral valve disease, accounting for almost three-fifths of patients aged 20 years or younger, and for almost four-fifths of those who needed surgery in the first 10 years of life. 38 As we have emphasised, it is the severity of the acute lesion, and the number of subsequent episodes, that determine the course of the disease. Unlike mitral stenosis, when there is a variable latent period between the establishment of the valvar lesion and the acute episode, mitral regurgitation is frequently present from the onset of the active process. Initial regurgitation has been noted to disappear over periods ranging from 2 months to 9 years, while new lesions such as mitral stenosis, or stenosis combined with regurgitation, appeared over a period of up to 12 years. 26 Patients with mitral regurgitation are far more likely to have suffered a more severe acute episode than those with mitral stenosis. 40 Significant insufficiency may progress rapidly, leading on to congestive heart failure. In contrast, a systolic murmur of mild valvar incompetence may well persist throughout the lifetime of the patient without any symptoms or further complications. In general, mild-to-moderate mitral regurgitation is better tolerated than similar degrees of mitral stenosis. Unlike mitral stenosis, isolated mitral regurgitation affects men more often than women.
Physiology
Mitral valvar regurgitation may be found early in the course of the acute episode, and pathological, haemodynamic, and functional changes are important determinants in the worsening of valvar incompetence. The valvar leaflets become thickened and retracted, with shortening and fusion of the tendinous cords also contributing to restricted valvar closure, which may be aggravated by dilation of the annulus and left atrium. The increased volume overload and output of the left atrium as a result of the regurgitation leads to an increased diastolic volume of the left ventricle, with dilation and hypertrophy of both chambers proportional to the severity of the valvar dysfunction. Hypertrophy of the muscle normalises left ventricular mural stress, and is appropriate for both the degree of volume load and the degree of dilation. 41 In those with moderate valvar incompetence, regurgitant flow from the left ventricle to atrium during systole is approximately half of the total ventricular stroke output. As the left ventricular end-diastolic volume is increased, in spite of the regurgitation into the left atrium, an adequate forward flow is maintained into the aorta during ventricular systole. The size of the left atrium is an important determinant of the rise in pressure in this chamber and in the pulmonary veins. In the setting of chronic disease, as the left atrium has time to dilate, the rise in pressure is relatively low. This factor, coupled with the lower energy cost of ventricular work, probably explains why moderate-to-severe mitral regurgitation is tolerated in many patients for a number of years. In contrast, in acute valvar incompetence with a normally sized left atrium, the left atrial pressure rises suddenly to a marked degree.
Severe mitral regurgitation is much better tolerated than an equal degree of aortic regurgitation. In chronic mitral regurgitation, the increased end-diastolic volume brings in the Frank–Starling mechanism, allowing a larger stroke output and increased left ventricular compliance. The increase in end-diastolic length of the myocytes, without a corresponding elevation in end-diastolic pressure, prevents a marked rise in pulmonary venous pressure. 42 Left ventricular end-diastolic pressure rises relatively minimally because of the compensatory change in left ventricular compliance, and the relations between left ventricular pressure and time remain normal. Ventricular function, therefore, is usually normal in children with mitral regurgitation. The favourable loading conditions often maintain the ejection fraction in the low normal range, and can make the left ventricular dysfunction imperceptible up to the later phases of the disease. 43 At this stage, the mean left atrial and pulmonary venous pressures rise, leading to a decreased pulmonary compliance and, subsequently, to pulmonary vasoconstriction. The mean pulmonary venous pressure is the major determinant of the resulting pulmonary arterial hypertension. Even with moderate-to-severe mitral regurgitation, though pulmonary arterial hypertension does occur, it does not reach the levels found in tight mitral stenosis. The forward stroke volume is maintained until late in the disease, when the regurgitant volume becomes so large that most of the stroke output empties into the left atrium. The forward stroke volume and cardiac output then decrease. A direct relationship exists between the regurgitant volume, the reduction in the forward stroke output, the elevation of the left atrial pressure, and the degree of clinical disability. 44
Clinical Features
The severity, and to a lesser extent the chronicity, of the regurgitant valve are the main factors in determining the symptoms. Those patients with mild lesions are completely asymptomatic. In patients with even moderate mitral regurgitation, symptoms may be relatively unimpressive. In contrast, in those with severe incompetence, there is effort dyspnoea, easy fatiguability, poor weight gain, palpitations on effort, paroxysmal nocturnal dyspnoea, and finally congestive heart failure. Paroxysmal or chronic atrial fibrillation and infective endocarditis are more common than in mitral stenosis. The susceptibility to thromboembolism, on the other hand, is smaller. 45,46 The jugular venous pressure is normal when there is no congestive heart failure, while normal blood pressure is associated with a slightly widened pulse pressure, giving a brisk pulse. The apical impulse is usually normal in those with mild lesions, with no major precordial pulsations. In significant mitral regurgitation, a hyperdynamic forcible left ventricular heaving apex is palpable, being displaced downwards and laterally. In general, the first heart sound is normal in intensity or somewhat soft. The second heart sound is usually normal, but can be markedly split in those with severe lesions because of the shortening of left ventricular systole. The presence of a loud third heart sound excludes the co-existence of significant mitral stenosis. The most important clinical feature is the characteristic apical systolic murmur. The murmur is pan- or holosystolic, starting with the first sound, which is often muffled. Indeed, it may well extend to the sound of closure of the aortic valve. It is heard best at the apex, radiates to the left axilla and left sternal edge, is unaffected by respiration, and has a blowing quality with no accentuation in mid- or late-systole. There is no definite correlation between the severity of the lesion and the length or intensity of the apical systolic murmur. Some patients with significant mitral regurgitation have a musical seagull murmur. The late systolic murmur of mild mitral regurgitation is often indistinguishable from that of the late systolic murmur found in patients with prolapsing leaflets of the mitral valve. 47 Occasionally, especially in the presence of acute valvitis, the murmur may be short, occurring in early mid- or late-systole. With severe valvar incompetence, a mid-diastolic blowing murmur is audible at the apex, caused by increased diastolic flow through the mitral valve and the turbulence created at the end of the rapid ventricular phase. This murmur, while it may be rumbling, does not extend to late diastole. It is usually shorter than the murmur heard in mitral stenosis. A low-pitched third heart sound, which is often palpable and is caused by the considerable early diastolic filling of the ventricle, is heard in those with significant mitral regurgitation. When there is associated pulmonary hypertension, its signs are present. These include a right ventricular parasternal lift, a loud palpable pulmonary sound, and murmurs of pulmonary and/or tricuspid incompetence. The clinical signs of mitral regurgitation are much less clear-cut than those of mitral stenosis.
The electrocardiogram may be normal when the regurgitation is mild. Even with moderate valvar incompetence, the features may be inconclusive. The P wave is broad, bifid or notched, and usually best seen in lead II or V 1 . A more reliable sign of left atrial enlargement is a terminal negative deflection of the P wave in lead V 1 of more than 0.04 seconds in duration and more than 1 mm in depth. Left ventricular hypertrophy occurs when mitral incompetence is more than moderate. There may be changes in the ST and T waves over the lateral chest leads when the valvar lesion is severe. In the presence of associated pulmonary hypertension, right ventricular hypertrophy, and right atrial enlargement are not uncommon ( Fig. 54B-10 ). Although uncommon in children and adolescents, atrial fibrillation occurs in patients with severe disease, and in those with long-standing chronic mitral regurgitation. The chest radiograph may be normal in patients with mild lesions. With well-established mitral regurgitation, the left atrium and the left ventricle are enlarged, their sizes being proportional to the degree of valvar dysfunction. There is pulmonary venous engorgement, especially in the upper lobes ( Fig. 54B-11 ). With the onset of pulmonary hypertension, the pulmonary trunk becomes prominent, and there is dilation of the right ventricle and atrium. Septal lines appear with the onset of cardiac failure.
The Doppler echocardiogram can be very useful, permitting highly sensitive and specific diagnosis of mitral regurgitation. In the M-mode echocardiogram, the EF slope of diastolic closure is not specific, nor does it indicate the severity of the valvar incompetence. There is an increase in the movements of the left ventricular septum and inferior wall because of the large stroke volume. In spite of difficulties in assessing left ventricular function because of the loading conditions in patients with chronic mitral regurgitation, the ejection fraction has been identified as a predictor of survival after surgical correction. 48 Thickening of the leaflets may be seen. Although the rheumatic leaflets may prolapse, the echocardiogram is useful in differentiating rheumatic disease from other causes of valvar prolapse, such as functional mitral regurgitation caused by severe cardiac dilation in primary cardiac muscle disease. The cross sectional echocardiogram in the long-axis view reveals a large, dilated, well-contracting left ventricle, and a dilated pulsatile left atrium. It also provides important information about the morphology of the valvar apparatus. The leaflets of the rheumatic valve are thickened and rigid, and the mural leaflet is frequently noted to be immobile. Cordal rupture, vegetations of infective endocarditis, and either presence or absence of left atrial thrombosis can all be recognised. Besides the morphological data, the severity of valvar incompetence can be assessed by mapping of the regurgitant jet and the width of the vena contracta, in addition to two quantitative methods used for evaluation of the regurgitant volume and calculation of the effective regurgitant orifice area 49–52 ( Figs. 54B-12 to 54B-14 ). In this setting, it is important to avoid over-diagnosis, since trivial incompetence can be seen even in normal subjects. Although rarely needed in children and adolescents, transoesophageal echocardiography is useful in patients in whom evaluation and quantification of the severity of mitral regurgitation has proved difficult when using the transthoracic windows. The valvar apparatus can now be accurately assessed by the three-dimensional technique. Exercise testing may be helpful in evaluating symptoms and establishing changes in exercise tolerance, particularly when it is difficult to obtain a reliable history. 43
Cardiac catheterisation and angiography are rarely indicated nowadays in patients with isolated mitral regurgitation. If performed, the mean left atrial or pulmonary capillary pressure is usually elevated, but in a small number of cases, aneurysmal dilation of the left atrium can produce a normal left atrial pressure despite significant regurgitation. 53 With significant valvar incompetence, the left atrial pressure is elevated, with a large V wave and a sharp Y descent. 54 A diastolic pressure gradient across the mitral valve can be found even in the absence of significant mitral stenosis. The left ventricular systolic pressures are usually normal, and end-diastolic pressure is normal unless there is left ventricular failure. Calculation of the valvar area by the Gorlin formula is less reliable in the setting of valvar incompetence. The regurgitant volume is measured as the difference between angiographically determined total left ventricular volume and the forward stroke volume using the Fick method, the fiberoptic technique, or the indicator dilution technique. 55–57 It can also be achieved by calculating the angiographically measured difference between the right and the left ventricular stroke volumes. 58 Selective left ventricular angiography in the 30-degree right anterior oblique projection profiles the left ventricle, left atrium, and mitral valve ( Fig. 54B-15 ). From a practical point of view, a qualitative estimation of severity from the amount of regurgitation into the left atrium of material injected into the left ventricle has been found useful. The degree of opacification of the left atrium depends on the quantity of blood in this chamber and on its rate of emptying, as well as on the severity of regurgitation. The width of the jet of mitral regurgitation is a good guide to the size of the regurgitant orifice. The left ventricular size, mural thickness and function, besides the degree of movements of the leaflets, can also be assessed. In patients with a decreased left ventricular ejection fraction, there will be an increased end-diastolic volume.
Mitral Stenosis
Mitral stenosis is a common chronic rheumatic valvar lesion, becoming established earlier than aortic stenosis. As with the other lesions, there is marked geographic variation. Mitral stenosis, in particular, appears precociously in patients from countries with high rates of the disease, probably due to repeated episodes of acute rheumatic fever associated with poor socioeconomic conditions. This is corroborated by some data from India, 26 showing a change in the pattern of valvar dysfunction according to the phase of the disease. While, in the initial acute attack, mitral regurgitation is frequently the only type of dysfunction present, subsequent episodes are accompanied by different combinations of valvar lesions. In most developing countries, mitral stenosis develops rapidly after the acute event, producing symptomatic young patients, and necessitating early surgical or catheter intervention. 38,59–62 In South Africa, one-fifth of patients with pure mitral stenosis had been treated surgically before the age of 20 years. 38 Similarly, of those treated by balloon valvoplasty in Saudi Arabia, over one-sixth were aged 20 or less. 63 Another series, from the United States, 64 although much smaller, revealed a tendency to milder mitral lesions, and more patients with isolated aortic regurgitation, reflecting the less severe outcome for patients in North America.
Physiology
Mitral stenosis in patients with rheumatic fever is caused by thickening and calcification of the leaflets, along with fusion of the ends of the zone of apposition between the leaflets and obliteration of the intercordal spaces. The resulting narrowing of the valvar orifice produces a barrier in diastolic left ventricular filling from the left atrium, and a gradient is established between the left atrial and left ventricular end-diastolic pressures. The rise in the left atrial pressure is reflected by the elevated pulmonary capillary or pulmonary wedge pressure. With critical mitral stenosis, there is severe left atrial and pulmonary venous hypertension. The pulmonary arterial pressure rises correspondingly to maintain an adequate pulmonary flow. Pulmonary arteriolar constriction, a result of a combination of vasospasm and pulmonary arteriolar disease, results in an elevated pulmonary vascular resistance. In the face of such persistent and significant pulmonary hypertension, there is right ventricular failure. In patients with mild-to-moderate elevation of left atrial pressure, exercise or sudden tachyarrhythmias may diminish the diastolic filling period, resulting in an abrupt elevation of the left atrial pressure. Pulmonary oedema may then occur. Pulmonary hypertension is initially passive. With alteration of pulmonary exchange of gases, and associated hypoxia and arteriolar vasoconstriction, obliterative pulmonary hypertension develops. Since the pulmonary venous pressure in critical mitral stenosis may exceed the oncotic plasma pressure of 30 mm Hg, the increased pulmonary vascular resistance is, to a large extent, a protective mechanism. Thickening of the capillary walls, interstitial tissues, and alveolar membranes produces a barrier at the interface between the capillaries and the alveolar sacs. In isolated mitral stenosis, the relationships between pulmonary pressure and flow are not constant. In some patients, the pulmonary circulation is maintained with only modest elevation of pulmonary arterial pressure, while in others pulmonary vascular disease becomes established, with severe hypertension pushing pulmonary pressures above the systemic level. Most patients with mild-to-moderate mitral stenosis, nonetheless, are able to maintain an adequate cardiac output with moderate exercise. In the presence of critical mitral stenosis, the cardiac output is low at rest. Exercise does not increase the cardiac output, which may even fall in the presence of significant pulmonary hypertension. The increased pulmonary pressure also causes tricuspid regurgitation. In patients who have had repeated episodes of rheumatic carditis, the severity and frequency of congestive heart failure is out of proportion to the severity of the valvar disease alone.
Clinical Features
The symptoms, physical signs, and amount of clinical disability parallel the severity of mitral stenosis. Those with minimal stenosis may be completely asymptomatic. Exercise and atrial fibrillation are among the precipitating causes of the initial presentation of symptoms, even in patients with mild-to-moderate mitral stenosis. 4 Critical or significant mitral stenosis is present when the area of the valvar orifice is reduced to about one-quarter of the expected normal for the age. The common symptoms in critical stenosis are effort dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, and episodes of pulmonary oedema. These symptoms may be aggravated by recurrence of carditis, intercurrent infections, and uncontrolled tachycardia or atrial fibrillation. Congestive cardiac failure usually occurs with severe stenosis and more than moderate pulmonary hypertension. The onset of atrial fibrillation usually indicates a relatively advanced stage of disease, and often accounts for worsening in its course. Atrial fibrillation and systemic embolisation, however, are uncommon in children and adolescents. 40,65 The systemic venous pressure is elevated in the presence of cardiac failure and pulmonary hypertension. This elevation is proportional to the severity of stenosis, and it becomes marked with the onset of cardiac failure or atrial fibrillation. The cardiac impulse is usually right ventricular, characteristically described as tapping in nature. When pulmonary hypertension is present, a parasternal lift is found, and pulmonary arterial pulsations, as well as closure of the pulmonary valve, are palpable. There are classic auscultatory findings in mitral stenosis. The first heart sound is accentuated because of an abrupt closure of the leaflets, which are held open until the beginning of ventricular systole. There is a loud, sharp, and high-pitched opening snap caused by a sudden tensing of the leaflets at the limit of their excursion of opening in diastole. A long, rumbling, low-pitched mid-diastolic murmur is heard at the apex, often with presystolic accentuation. In the absence of associated mitral regurgitation, the duration of the diastolic murmur is directly proportional to the severity of the stenosis. The duration of the murmur may be altered by the presence of a fast ventricular rate or congestive heart failure. The murmur is best heard in the lateral position, using the bell of the stethoscope. It is augmented by exercise. Should the patient develop atrial fibrillation, then there is usually loss of the presystolic accentuation. The presence of a pulmonary ejection click and an accentuated pulmonary component of the second sound, along with murmurs of pulmonary and tricuspid regurgitation, indicate severe pulmonary hypertension.
The electrocardiogram shows evidence of left atrial enlargement. Broad, notched P waves are seen in the limb leads, or a biphasic P wave in leads V 1 and V 2 , with a marked negative component. Right atrial enlargement, right-axis deviation, and right ventricular hypertrophy of varying degrees reflect the severity of the pulmonary hypertension ( Fig. 54B-16 ). The chest radiograph shows varying degrees of left atrial enlargement, which displaces the oesophagus backwards, with elevation of the left main bronchus and widening of the carina. The enlarged left atrial appendage may be visible on the left cardiac border ( Fig. 54B-17 ). In the presence of pulmonary hypertension, the pulmonary trunk and the right chambers are enlarged. The aorta is usually normal or small. The degree of left atrial enlargement is usually less in isolated mitral stenosis than in mitral incompetence. With mild pulmonary venous hypertension, there is initially distention only of the pulmonary veins from the lower lobes, which may be difficult to identify clearly. Once there is significant pulmonary venous hypertension, there is interstitial oedema in the lower zone, and vasoconstriction in the veins supplying them. The flow of blood is then increased in the veins to the upper lobes, which are dilated, producing differential pulmonary venous circulation. Kerley’s A and B lines are seen because of interstitial oedema and small interlobar effusions. Acute pulmonary oedema is recognised by the typical perihilar opacity, with radiations to the periphery. Exercise testing may be helpful in cases with discrepancy between haemodynamic data and symptoms. 43
