US Pharm. 2020;45(2):HS-2-HS-6.
ABSTRACT: Rheumatic heart disease (RHD) is a major problem in developing countries and is the cause of most of the cardiovascular mortality in young people. Acute rheumatic fever, the precursor to rheumatic heart disease, can affect various organs and lead to irreversible valve damage and heart failure. Treatment guidelines have emphasized antibiotic prophylaxis against recurrent episodes of acute rheumatic fever. Early diagnosis and treatment are possible if people at risk for RHD in endemic areas are screened. Echocardiographic screening has played a key role in improving the accuracy of diagnosing RHD and has highlighted the disease burden.
Rheumatic heart disease (RHD) is characterized by permanent damage to the valves of the heart that develops as a serious consequence of repeated episodes of acute rheumatic fever (ARF), an autoimmune reaction to a group A streptococcus (GAS) bacterial infection. Heart failure, atrial fibrillation, and stroke are common complications of RHD, resulting in significant premature morbidity and mortality.1-3 Though successfully eradicated in developed countries, RHD is still the most common global cardiovascular disorder in individuals younger than age 25 years. Its continued high prevalence in developing countries translates into high numbers of heart valve surgeries, which economically burdens both patients and the respective health ministries.4
EPIDEMIOLOGY AND RISK FACTORS
In 2015, there were approximately 320,000 deaths from RHD and 33 million individuals living with RHD. In sub-Saharan Africa, South Asia, and Oceania, the overall prevalence of RHD was estimated at 10 to 15 cases per 1,000.5 RHD occurs in 60% to 65% of patients, although figures vary.6 The African, South-East Asian, and Western Pacific regions are the worst affected, accounting for 84% of all prevalent cases and 80% of all estimated deaths due to RHD in 2015. Rheumatic heart disease disproportionately affects girls and women.7 The risk of RHD is 1.6 to 2.0 times greater in women, likely due to several factors, including worsening of existing disease during pregnancy, GAS exposure during child rearing, limited access to services, and intrinsic/hormonal factors. Socioeconomic and environmental factors such as overcrowding, poor housing conditions, undernutrition, and lack of access to healthcare play a role in the persistence of this disease in developing countries.8
Echocardiography is the gold standard for diagnosis of RHD. Systematic screening with echocardiography, as compared with clinical screening, reveals a much higher prevalence of RHD (approximately 10 times as great).9 Echocardiography is recommended to identify patients with subclinical rheumatic carditis. Patients with mild RHD that may not be clinically detectable are at increased risk for death and complications from other heart-related causes. For example, transient or sustained atrial fibrillation is sometimes observed in clinically asymptomatic patients with mild or moderate rheumatic mitral stenosis, which is often diagnosed on echocardiography after complications, such as stroke, have occurred.10
World Heart Federation Criteria
The World Heart Federation has established criteria for echocardiographic diagnosis of RHD that categorizes the disease as either definite or borderline for individuals aged 20 years or younger (Table 1). In brief, definite RHD requires the combination of at least 2 morphologic criteria with pathologic regurgitation or mitral stenosis or borderline disease of the aortic and mitral valves. Borderline RHD is defined by at least 2 morphologic features or the presence of pathologic mitral or aortic regurgitation.9,11 Echocardiography has proven to be more sensitive and specific than auscultation. RHD detected on echocardiography without an associated clinically pathological cardiac murmur is referred to as subclinical RHD. Echocardiographic changes that meet the criteria for definite RHD are considered to be rheumatic in origin, provided that other etiologies have been excluded by echocardiography and clinical context.12
Clinical diagnosis of RHD using the Jones criteria is based on pathological valvular heart murmur detected during auscultation. Based on the major criteria (more frequent clinical findings) established by Jones and revised by the American Heart Association, the disease manifests as carditis (50% to 60%), polyarthritis, chorea, erythema marginatum, and/or subcutaneous nodules.13 Sydenham’s chorea, caused by infection with GAS, is a major criteria for ARF and is characterized by involuntary movements, especially of the face and limbs, muscular weakness, and disturbances of speech, gait, and voluntary movements.13,14 Acute rheumatic carditis usually presents as tachycardia and cardiac murmurs with or without transient rhythm disturbances (reflecting myocardial involvement) or a friction rub (reflecting pericarditis). Moderate-to-severe rheumatic carditis can result in cardiomegaly and congestive heart failure with hepatomegaly and peripheral and pulmonary edema. Rheumatic carditis is the only manifestation that may result in long-term disability or death.15 Aside from a subset of children in whom rheumatic fever (RF) leads to severe carditis and early RHD, RHD is usually clinically silent (“latent”) until it manifests during adulthood. Many individuals in RHD-endemic countries present late in their disease process with one or more sequelae, which can include heart failure, atrial fibrillation, stroke, and infective carditis, among others.16
MANIFESTATIONS OF RHD
The most common form of RHD affects the heart valves and is almost always associated with a murmur of valvulitis, making it a hallmark sign of RHD. Mitral valve incompetence is the most common valvular lesion in patients with RHD, particularly in the early stages. Mitral stenosis usually develops later as a result of persistent or recurrent valvulitis with bicommissural fusion, although mitral stenosis has been described in adolescents. Aortic regurgitation is most often associated with some degree of mitral regurgitation, but it can be isolated and severe. Tricuspid regurgitation is often functional, mainly caused by mitral stenosis with high pulmonary pressures and consequent right ventricular dilatation. Isolated pulmonary and tricuspid regurgitation are not classic features of RHD. The disease might also present after a complication such as atrial arrhythmia, an embolic event, acute heart failure, or infective endocarditis.17 A ﬁrst episode of rheumatic carditis should be suspected in a patient who does not have a history suggestive of previous RF or RHD, and who develops a new apical systolic murmur of mitral regurgitation (with or without an apical mid-diastolic murmur), and/or the basal early diastolic murmur of aortic regurgitation. On the other hand, in an individual with previous RHD, a deﬁnite change in the character of any of these murmurs or the appearance of a new, signiﬁcant murmur indicates the presence of carditis.
Myocarditis alone, in the absence of valvulitis, is unlikely to be of rheumatic origin and by itself should not be used as a basis for such a diagnosis. It should always be associated with an apical systolic or basal diastolic murmur. Clinically apparent congestive heart failure (CHF) and radiographic cardiac enlargement indicate that the myocardium is likely to be involved in the primary episode of RF, although the role of unexplained CHF in the diagnosis of a recurrence of rheumatic carditis has been questioned.17
Pericardial involvement in RF may result in distant heart sounds, a friction rub, and chest pain. At times, however, the friction rub can mask the mitral regurgitation murmur, which becomes evident only after the pericarditis subsides. Since isolated pericarditis is not good evidence of rheumatic carditis without supporting evidence of a valvular regurgitant murmur, Doppler echocardiography may be helpful in such circumstances to look for signs of mitral regurgitation.18
PREVENTION STRATEGIES FOR RHD
The major interventions for prevention and control of RHD include reduction of exposure to GAS; primary prophylaxis to prevent initial episodes of RF; and secondary prophylaxis to prevent recurrent episodes of RF. Because recurrent episodes of RF cause increasingly severe cardiac complications, secondary prophylaxis is the most crucial feature of an effective RHD program. Tertiary prophylaxis is used to prevent complications once RHD is established.19,20 Prevention strategies are the most appealing option for sustainable disease control in developing nations.
Primordial prophylaxis essentially focuses on socio-economic development as it directly impacts hygiene, access to medical care, and living conditions (such as avoidance of overcrowding).21
Primary prevention of RHD depends on preventing the initial attacks of ARF by means of short-term oral or IM penicillin treatment of patients presenting with acute sore throat (pharyngitis) caused by GAS infection. Barriers to primary prevention in developing countries include poor access to primary care, a shortage of skilled personnel, the expense of microbiological diagnosis, poor public awareness about the diagnosis and prompt treatment of suspected GAS pharyngitis, and a high incidence of ARF without sore throat. Yet primary prevention has been less widely adopted in developing countries. This is because of both barriers to its implementation and a concern about its cost-effectiveness.22
The World Health Organization defines secondary prophylaxis as “the continuous administration of specific antibiotics to patients with a previous attack of rheumatic fever, or well-documented rheumatic heart disease. The purpose is to prevent colonization or infection of the upper respiratory tract with group A beta-hemolytic streptococci and the development of recurrent attacks of rheumatic fever.” The minimum duration of secondary prophylaxis in most guidelines is 10 years. In severe cases, lifelong regular benzathine penicillin G administration may be recommended.23
Tertiary interventions for RHD include medical management of heart failure, operative management of valve lesions, and treatment for the consequences of RHD, including stroke, infective endocarditis, and arrhythmia.24
RHD is one of the most common and preventable acquired heart diseases, with valvular heart damage as the hallmark. Although the number of cases in developed countries has been reduced drastically, the same cannot be said of developing countries.25 There are multiple opportunities to intervene along the strep A to RHD pathway and prevent morbidity and mortality. Echocardiography allows earlier detection, when penicillin remains an effective and affordable prophylaxis against progressive valvular disease.26 In a disease like RHD, accurate diagnosis is a particularly critical issue: A false-positive diagnosis will expose the patient to inappropriate and lengthy treatment (usually 10 years or longer), potentially create psychological harm and stigmatization by association with a disease (there is even evidence that echocardiographic RHD screening alone lowers quality- of-life scores for both the caregiver and screened child), and unnecessarily add to the financial and manpower burden of the already stretched healthcare systems of many developing countries. Conversely, a false-negative result risks missing the opportunity to prevent a potentially fatal disease.27
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