Introduction
In developing countries, rheumatic carditis tends to affect cardiac valves leading to their rapid deterioration due to repeated episodes of acute rheumatic fever. It is estimated that 15.6 million people suffer from RHD worldwide, with nearly 233,000 related deaths each year (Carapetis J. et al., 2005).
Mitral valve is the most commonly affected cardiac valve, then aortic, tricuspid and pulmonary valves in order. In majority of cases, the mitral valve is involved with one or more of the other three. In acute disease, small thrombi form along the planes of valve closure. In chronic disease, there is thickening and fibrosis of the valve leading to stenosis, or less commonly, regurgitation (Marijon E. et al., 2012).
Rheumatic fever is a late inflammatory, nonsuppurative complication of pharyngitis caused by group A-hemolytic streptococci. It results from humeral and cell-mediated immune responses occurring one to three weeks after the onset of streptococcal pharyngitis (Burke A., 2013).
Streptococcal proteins display molecular mimicry recognized by the immune system, especially bacterial M-proteins and human cardiac antigens as myosin and valvular endothelium. Antimyosin antibody recognizes laminin, an extracellular matrix alpha-helix coiled protein, which is part of the valve basement membrane structure (Steer et al., 2009).
T-cells that show response to the streptococcal M-protein infiltrate the valve through the valvular endothelium, activated by the binding of antistreptococcal carbohydrates with release or tumor necrosis factor (TNF) and interleukins. The acute involvement of the heart in rheumatic fever leads to pancarditis, with inflammation of all layers, the myocardium, pericardium, and endocardium. Carditis occurs in approximately 40-50% of patients on the first attack; however, the severity of acute carditis is questionable. Pericarditis occurs in 5-10% of patients with rheumatic fever, while occurrence of isolated myocarditis is rare (Guilherme et al., 2004).
Familial studies of rheumatic heart disease suggest a vulnerable population with increased risk. There is a clear relationships between the development of rheumatic fever and human leukocyte antigen (HLA)-DR subtypes (Burke A. et al., 2013).
Mitral valve is the most commonly affected cardiac valve, then aortic, tricuspid and pulmonary valves in order. In most cases, the mitral valve is involved with one or more of the other three. In acute disease, small thrombi form along the lines of valve closure. In chronic disease, there is thickening and fibrosis of the valve resulting in stenosis, or less commonly, regurgitation, that will be discussed in details (Marijon E. et al., 2012).
In Egypt, rheumatic heart disease was rampant in 1950’s. There is slow and steady decline in the prevalence of the disease but does not reach the ideal goals. Unfortunately, if affects young adults during their most productive years in addition to the economic burden of the involved families and the whole nation as well (Sorour, 2014).
Minia Governorate is considered as one of the most populous governorates in Egypt and being one of the poorest in the country. Screening of the prevalence of RHD there was not available till 2011 when that El-Aroussy and colleagues accomplished a study of screening for RHD among school-age children and abnormal combination of mitral valve affection was the dominant feature in about 65.9% (El-Aroussy et al., 2013). This study followed by another one held by Taha N. and his colleagues who screened for cardiac abnormalities in pregnant women admitted to Gynecology and Obstetrics department in Minia University. They stated that 78% of them had valvular heart disease, almost due to rheumatic etiology and more than 60% had mitral valve disease either mitral regurgitation, mitral stenosis or both and they concluded that rheumatic RHD is the commonest cardiac lesion among pregnant women in Minia governorate (Taha N. et al., 2012).
It stated that echocardiographic screening of schoolchildren may underestimate the true prevalence of rheumatic heart disease, since the major risk factors for rheumatic fever include poverty, overcrowdance, and poor access to medical services, all of which are probably associated with a reduced likelihood of attending school. However, this prevalence rate, we observed in two populations of children with an average age ranging between 6 and 18 years, is similar to community data reported from Australian aborigines, that suggest a much higher prevalence of rheumatic heart disease in children over 15 years of age (Mariojin et al., 2007, El-Aroussy et al., 2013).
i. Mitral stenosis
The predominant cause of mitral stenosis (mitral stenosis) is rheumatic carditis. Isolated mitral stenosis occurs in 40% of all patients presenting with RHD, and a history of RF can be elicited from approximately 60% of them (Bonow et al., 2008). Thus, mitral stenosis is highly prevalent in developing countries because of its association with the prevalence of RF, but is also seen in developed countries (Chandrashekhar et al., 2009).
The pathological process by which the RF causes mitral stenosis includes leaflet thickening and calcification, commissural fusion, chordal fusion, or a combination of these processes (Bhandari et al., 2007).The result is a funnel-shaped mitral apparatus in which the orifice of the mitral opening is decreased in size (Bonow et al., 2008).
The normal mitral valve orifice is 4 to 6 cm2, with a reduction in MVA by the rheumatic process, it curtails free flow of blood from LA to LV, and a pressure gradient develops between the 2 chambers which added on LV diastolic pressure resulting in increasing LA pressure that leads to LA enlargement and pulmonary congestion (Carabello 2005).
Increased pressure as well as pulmonary venous and capillaries distension can lead to pulmonary edema when pulmonary venous pressure exceeds that of plasma oncotic pressure. In patients with chronic mitral stenosis, even when it is severe and pulmonary venous pressure is very high, pulmonary edema may not occur due to a marked decrease in pulmonary microvascular permeability (Bonow et al., 2008).
As stenosis severity worsens, flow restriction limits LV output. Ejection phase indexes of LV function are reduced in approximately one third of patients with mitral stenosis, as; decreased preload from impaired filling and increased afterload secondary to reflex vasoconstriction (due to reduced COP) are usually the causes of reduced LV function rather than impaired contractility. However, in developing countries where rheumatic inflammation is very aggressive, true contractile impairment may be present (Carabello 2005).
It is primarily the RV that generates the force necessary to drive blood across the stenotic mitral valve, so; mitral stenosis causes RV pressure overload (Carabello 2005). In severe mitral stenosis, pulmonary hypertension results from: elevated LA pressure resulting in passive backward transmission into the pulmonary vasculature, pulmonary arterioles may react with vasoconstriction, organic obliterative changes in the pulmonary vascular bed (intimal hyperplasia, and medial hypertrophy) (Bhandari et al., 2007).
Subsequently, over a period of time, severe pulmonary hypertension leads to right-sided HF, with dilatation of the RV and its annulus, secondary tricuspid and sometimes pulmonic regurgitation (Bhandari et al., 2007).
Symptoms start when MVA reduces to 1.5 cm2, and most patients have evident symptoms when the area is less than 1 cm2 (Chandrashekhar et al., 2009). However, symptoms often occur in patients with larger valve areas if the time of diastolic filling decreases and/or transmitral flow increases, as is the case with exercise, anemia, AF, pregnancy, infection, or emotional stress (Maganti et al., 2010).
Patients with persistent severe mitral stenosis develop compensatory changes (eg, pulmonary arterial hypertension, dilated lymphatic vessels, and alveolar thickening) that moderate symptoms for a short period. Left-atrial and left-ventricular compliance change due to age and pulmonary arterial hypertension can also affect symptoms and exercise capacity (Chandrashekhar et al., 2009).
Mitral stenosis severity is based on a variety of hemodynamic and natural history data as following:
Diagnosis
1- History
The course of mitral stenosis is slow and steady in the early years then shows a progressive acceleration later in life (Bhandari et al., 2007).
Serial hemodynamic and Doppler echocardiographic studies reported that annual loss of mitral valve area ranging from 0.09 to 0.32 cm2/year which explains the variable onset of symptoms (Chandrashekhar et al., 2009).
In mild disease the patient may be entirely asymptomatic; with worsening stenosis the first symptoms of mitral stenosis are usually exertional dyspnea and easy fatigueability (Maganti et al., 2010).
In some patients, the new onset of atrial fibrillation with embolic episodes may be the first presentation of mitral stenosis. In other patients, the physiological stress of pregnancy may cause symptoms for the first time (Carabello 2005).
Other rare symptoms include hemoptysis, chest pain and pressure effects on adjacent structures from dilated LA; as hoarseness (Ortner’s syndrome) due to pressure on left recurrent laryngeal nerve or dysphagia (Chandrashekhar et al., 2009). Hemoptysis results in patients with mitral stenosis due to (1) rupture of thin-walled, dilated bronchial veins leading to pulmonary apoplexy (2) attacks of paroxysmal nocturnal dyspnea (3) acute pulmonary oedema with rupture of alveolar capillaries (4) Pulmonary infarction, late and associated with heart failure (5) Chronic bronchitis resulting due to presence of oedematous bronchial mucosa (Bhandari et al., 2007).
2- Physical Examination
The physical examination of the patient with mitral stenosis is characteristic and usually diagnostic (Carabello 2005). Diagnostic sensitivity and specificity is about 85% and accuracy is similar to that of echocardiography about 92% vs 97%. Important clinical issues are severity of disease, pliability of the valve, pulmonary arterial hypertension and presence of AF (Chandrashekhar et al., 2009).
In advanced disease, the pulse pressure may be reduced, which indicates reduced SV. There may be typical “mitral†facies with plethoric cheeks punctuated by bluish patches due to impaired COP, neck vein elevation is seen if there is right HF and lung examination may demonstrate rales (Carabello 2005).
In Cardiac examination classic findings include: a normal apical LV impulse, an accentuated S1, and an OS followed by a diastolic rumble with presystolic accentuation heard best at the apex in the left lateral decubitus position. These findings may not be present in patients with severe pulmonary hypertension, low cardiac output or a heavily calcified and immobile valve (Maganti et al., 2010).
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The severity of disease is assessed from symptoms, presence of long murmur (especially with presystolic accentuation in normal sinus rhythm or during long RR intervals in AF), short interval of A2 to OS (≤ 0.08 seconds), and signs of pulmonary arterial hypertension. Pliability of the valve is assessed from loud S1 and prominent OS (Chandrashekhar et al., 2009).
In patients with pulmonary hypertension, the pulmonic component of S2 will be increased in intensity; other findings may include a tricuspid murmur, hepatomegaly, ascites, and edema (Carabello 2005).
3- Diagnostic Testing
Chest Radiography:
The most common chest radiographic finding in patients with severe mitral stenosis is left atrial enlargement, enlargement of the right atrium, right ventricle, and pulmonary artery occurs in advanced mitral stenosis with pulmonary hypertension (Maganti et al., 2010).
Electrocardiography:
In mitral stenosis the ECG is often normal, pathological changes in the ECG include;(a) left atrial enlargement that causes P mitrale, increased voltage in the later part of the P wave gives it a large, bifid appearance in leads II, III and aVF (b) AF is present in 60 to 70% (c) RV hypertrophy: dominant R wave in V1 and V2 indicates pulmonary hypertension (d) right axis deviation (Otto and Bonow, 2007).
Echocardiography:
The diagnostic tool of choice in the evaluation of a patient with mitral stenosis is 2D echo and Doppler echocardiography (Bonow et al., 2008). Echocardiography is able to identify restricted diastolic opening of the MV leaflets due to doming (hockey stick deformity) of the anterior leaflet and immobility of the posterior leaflet , also provides information regarding the size of the LA and the size and function of the LV and the right-sided chambers (Maganti et al., 2010).
2D echo can be used to assess the morphological appearance of the MV apparatus, including leaflet mobility, flexibility, thickness, calcification, subvalvular fusion, and the appearance of commissures, these features may be important to consider the timing and type of intervention to be performed, chamber size and function and other structural valvular, myocardial, or pericardial abnormalities can be assessed also (Bonow et al., 2008).
The most reliable method to calculate MVA is planimetry with 2D echo cross-section images and more reliability might be achieved with 3D echo. Another common assessment method for MVA is pressure half-time (the time taken for the pressure to halve from the peak value) which is most effective for the native valve before surgical intervention (Chandrashekhar et al., 2009).
Doppler echocardiography provides information about the severity of mitral stenosis, the presence of other associated valve lesions, and the degree of pulmonary hypertension (Maganti et al., 2010).
Cardiac Catheterization:
Coronary angiography is performed in patients scheduled to undergo valve replacement surgery if there is a risk of CAD (Maganti et al., 2010).
Exercise Testing:
Exercise testing using either a treadmill or supine bicycle is useful to determine functional capacity, particularly if it is difficult to establish the presence of symptoms by history (Maganti et al., 2010).
Doppler echocardiography combined with exercise provides additional important hemodynamic data regarding the severity of the MV gradient and pulmonary artery pressure during exercise because symptoms are often most pronounced at higher heart rates (Bonow et al., 2008).
ii. Mitral regurgitation
Rheumatic disease remains a major cause of mitral regurgitation (mitral regurgitation) in developing countries (Pedrazzini al., 2010).The mechanism of regurgitation is leaflet restriction with reduced motion described both in systole and in diastole, so this is distinguished from functional mitral regurgitation where the primary abnormality is the left ventricle (McCarthy et al., 2010).
Rheumatic mitral regurgitation causes retraction of tendinous chords and leaflets, as well as annular dilatation, thus compromising coaptation between the two leaflets (Pedrazzini et al., 2010).
The clinical impact of mitral regurgitation is determined by the regurgitant volume (Rvol) and the time of development of the regurgitation (Gaasch and Meyer, 2008).The degree of mitral regurgitation is defined by lesion severity (measured as effective regurgitant orifice (ERO) area and the yielding volume overload measured as Rvol, but it is also affected by the driving force (left-ventricular systolic pressure) and left-atrial compliance (Enriquez-Sarano M et al., 2009).
Thus; in acute mitral regurgitation the LA is noncompliant, and therefore mechanical energy generated by the LV causes an increase in intra-atrial pressure (LA pressure V-wave), while in chronic mitral regurgitation the LA is more compliant, and therefore mechanical energy generated by the ventricle causes volume overload and LA enlargement rather than an increase in intra atrial pressure (Pedrazzini et al., 2010).
Acute and chronic mitral regurgitation differs dramatically in their presentation and required management. In acute mitral regurgitation; remodeling does not occur and the patient usually present with symptomatic heart failure (HF), while chronic regurgitation of the mitral valve enables LV dilatation and remodeling, thereby maintaining forward stroke volume (SV) and cardiac output (COP) (Mokadam et al., 2011).
Patients with chronic mitral regurgitation have progressively worsening LV function; this is initially helped by the addition of the LA regurgitant volume to the forward SV leading to improve forward COP and EF (Athanasiou et al., 2008). Chronic LV volume overload leads to contractile dysfunction, heart failure and increased risk of sudden death (Pedrazzini et al., 2010).
Advanced myocardial dysfunction may occur while LV EF is still within the normal range (Enriquez-Sarano et al., 2005). The LV EF in chronic mitral regurgitation may be greater than normal because of the increase in preload and the afterload-reducing effect of ejection into the low impedance LA, therefore LV ejection fraction can be misleading as a measure of contractile function in this disorder (Maganti et al., 2010).
Diagnosis:
1. History:
In evaluating the patient with chronic mitral regurgitation, the history is invaluable, as patients with mild to moderate mitral regurgitation (compensated) may remain asymptomatic for many years (Bonow et al., 2008). Decompensation may eventually develop if the regurgitation is sufficiently severe (Maganti et al., 2010).
2. Physical Examination
A well-established estimation of baseline exercise tolerance is important in determining the onset of symptoms at subsequent evaluations (Bonow et al., 2008). Initial clinical assessment looks for symptoms, signs of HF, and physical signs of severe mitral regurgitation; displaced apical impulse, systolic thrill, loud systolic murmur, S3, early diastolic rumble, and AF. These signs are important but not specific enough to rely solely on them to suggest surgery (Enriquez-Sarano M et al., 2009).
The usual and most obvious symptoms of acute mitral regurgitation are dyspnea, hemodynamic instability, and shock (including weakness, dizziness, and altered mental status) , however, these findings can be nonspecific, as some patients with acute mitral regurgitation present solely with new-onset dyspnea without evidence of impending cardiovascular collapse (Mokadam et al., 2011).
3. Diagnostic Testing
Chest Radiography:
Cardiomegaly due to left ventricular and left atrial enlargement is common in patients with chronic mitral regurgitation, right-sided chamber enlargement is also a common finding in patients with pulmonary hypertension (Maganti et al., 2010).
Electrocardiography:
Left atrial enlargement and atrial fibrillation are the most common ECG findings in patients with mitral regurgitation, LV enlargement is noted in approximately one-third of patients, and RV hypertrophy is observed in 15% (Otto and Bonow, 2007).
Echocardiography:
Provides information about the mechanism and severity of mitral regurgitation, the size and function of the LV and RV, the size of the LA, the degree of pulmonary hypertension and the presence of other associated valve lesions (Zoghbi et al., 2003).
Doppler color flow imaging is used to estimate the severity of mitral regurgitation, the amount of regurgitant jet within the antecedent chamber (LA) is directly proportional to the severity of valve regurgitation (Apostolakis and Baikoussis, 2009).
Transoesophageal echocardiography (TEE) is superior to transthoracic echocardiography (TTE) for assessing the precise anatomy of the valve and mitral regurgitation severity, also mandatory when transthoracic images are of suboptimal quality (Pedrazzini et al., 2010).
Specific parameters that are important for clinical decision making are the degree of LV dilation, LV systolic function, LA enlargement and pulmonary hypertension (Meier et al., 2002).
Exercise testing is useful in determining functional capacity, particularly when symptoms are unclear (Enriquez-Sarano M et al., 2009).
Cardiac Catheterization:
Coronary angiography is indicated for patients who are planning to undergo surgery and are at risk of CAD, also performed to assess the hemodynamic severity of mitral regurgitation when noninvasive testing is inconclusive or a discrepancy exists between clinical and noninvasive findings (Maganti et al., 2010).
Angiographic evaluation of regurgitant severity is based on ejection of contrast media into the LA through the affected mitral valve and the severity of regurgitation is graded on a semi quantitative scale of 1+ to 4+ (Apostolakis and Baikoussis, 2009).