Screening for Rheumatic Heart Disease—Quo Vadis?

Abstract

Although mostly banished from Western training curricula, rheumatic heart disease (RHD), described as the malady that "licks the joints but bites the heart," 1(p1) continues to be responsible for major cardiovascular morbidity and mortality in the developing world. 2,3 Rheumatic heart disease constitutes a double tragedy because it disproportionately affects economically disadvantaged people and young people, thereby robbing them of the most productive years of life. Often, by the time it is diagnosed, RHD has resulted in substantial valvular damage. Dealing with such established disease frequently necessitates cardiac surgery or catheter-based procedures, requiring tertiary care setups and significant financial resources, often beyond the reach of most people in the developing world. Therefore, the idea of diagnosing RHD at an early stage with the aim of preventing disease progression is a worthwhile goal. Despite multipronged research in the field, including efforts at a vaccine, 4 the only preventive strategy proven to make a difference thus far is antibiotic prophylaxis to prevent acute rheumatic fever recurrences.How can we detect disease early? The concept of screening by echocardiography at a population level was proposed more than a decade ago based on the limited sensitivity of auscultation to diagnose disease, especially in its early stages, but is yet to progress beyond the realm of research. 5,6 It is now well established that echocardiography can detect up to a 20-fold higher disease prevalence compared with clinical examination alone. 7 However, crucial issues that need to be addressed with respect to screening include the accuracy and standardization of diagnosis, understanding the natural history of milder forms of disease (latent RHD), whether antibiotic prophylaxis administered early can prevent progression, and the cost-effectiveness of screening programs.In this issue of the JAMA Cardiology, Karki et al 8 address some of these important issues. They performed a cluster randomized comparison in 32 schools in Nepal, involving a total of 3973 children. Echocardiographic screening was performed in 17 experimental schools but not in 15 control schools. Screening with portable echocardiography machines was initially performed by 2 trained physicians, with patients with suspected RHD undergoing confirmatory additional echocardiography at a tertiary institute. Children detected to have definite or borderline RHD were enrolled in a registry and followed up annually. Children with definite RHD detected at any time but not borderline RHD were prescribed antibiotic prophylaxis. Follow-up echocardiographic examinations were performed in experimental and control schools after a median duration of 4.3 years. A lower prevalence, although

Potential Involvement of M1 Macrophage and VLA4/VCAM-1 Pathway in the Valvular Damage Due to Rheumatic Heart Disease

“…Previous studies have shown the existence of cross antigens between the M protein of GAS and cardiac proteins such as myosin, laminin and vimentin. The antigen-antibody cross-reaction triggers a large number of inflammatory cells to infiltrate the cardiac valve, leading to inflammatory damage [9][10][11][12][13]. Previous studies have also reported infiltration of CD4 + lymphocytes into the neovascularization area of RHD valves [47].…”

“…A potential connection exists between pathological changes in heart valves and the pathogenesis of RHD, with valvular disease being the most common type of RHD [8]. The occurrence of valve lesions is related to the presence of cross antigens between heart tissue and the M protein of GAS, causing immune cells to mistakenly attack the heart valves [9][10][11][12][13]. Our previous research demonstrated significant infiltration of inflammatory cells into the heart valves of RHD model rats [14,15].…”

Rheumatic Heart Disease—A Neglected Tragedy in Young Patients

“…The real need is to identify individuals expeditiously and institute timely antibiotic prophylaxis to prevent advanced disease. 10 Although Karthikeyan and colleagues mainly argue for an augmentation of tertiary care services to reduce RHD mortality, it needs to be borne in mind that mechanical valve replacement in young patients in some ways constitutes a disease in itself given the need for lifelong warfarin use, regular monitoring, and attendant possible complications of bleeding and thrombosis. This is especially problematic in women of reproductive age, where pregnancy with a mechanical valve can result in both maternal and fetal morbidity.…”

“…In economically deprived settings, people often do not seek medical care until late, curtailing valuable opportunities to halt disease progression earlier. The real need is to identify individuals expeditiously and institute timely antibiotic prophylaxis to prevent advanced disease . Although Karthikeyan and colleagues mainly argue for an augmentation of tertiary care services to reduce RHD mortality, it needs to be borne in mind that mechanical valve replacement in young patients in some ways constitutes a disease in itself given the need for lifelong warfarin use, regular monitoring, and attendant possible complications of bleeding and thrombosis.…”