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Table of Contents
REVIEW ARTICLE
Year : 2021  |  Volume : 11  |  Issue : 4  |  Page : 161-165

Rheumatic heart disease: Is it reversible?


Department of Cardiology, Medicover Hospitals, Hitec City, Hyderabad, Telangana, India

Date of Submission09-Jun-2021
Date of Acceptance05-Oct-2021
Date of Web Publication25-Oct-2021

Correspondence Address:
Dr. Kumar Narayanan
Department of Cardiology, Medicover Hospitals Hitec City, Hyderabad - 500 081, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jicc.jicc_36_21

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  Abstract 


Rheumatic heart disease (RHD) continues to be responsible for the loss of millions of young productive lives worldwide, with a disproportionate burden being borne by the underdeveloped and economically disadvantaged strata of society. There is an urgent need to develop approaches to identify RHD in its early stages and reverse it before it can cause significant valvular damage. This is especially relevant for the developing world where advanced cardiac surgery is inaccessible to many. Research over the last decade has made it possible to diagnose subclinical or latent RHD through systematic echocardiographic screening using standardized criteria, which can pick up early disease better compared to clinical screening alone. Furthermore, initial studies show promise that timely institution of penicillin prophylaxis can lead to regression of such latent disease. This brief review summarizes the current state of the field in this regard and outlines some of the challenges in translating this concept from benchside to public health policy.

Keywords: Echocardiography, latent, prophylaxis, rheumatic heart disease, screening, subclinical


How to cite this article:
Narayanan K. Rheumatic heart disease: Is it reversible?. J Indian coll cardiol 2021;11:161-5

How to cite this URL:
Narayanan K. Rheumatic heart disease: Is it reversible?. J Indian coll cardiol [serial online] 2021 [cited 2021 Dec 5];11:161-5. Available from: https://www.joicc.org/text.asp?2021/11/4/161/329146




  Introduction Top


The developing world, including India, is facing a double burden of infectious as well as lifestyle diseases due to an ongoing epidemiologic and demographic transition.[1] Thus, while we are faced with burgeoning noncommunicable diseases including diabetes and ischemic heart disease, we continue to battle the traditional infectious caseloads of malaria, tuberculosis, and childhood diarrhea. A disease which can be said to sit at the cusp of these two entities is rheumatic heart disease (RHD), which, while being primarily infectious in its etiology, imposes a tremendous burden on tertiary cardiovascular resources. RHD has been largely eradicated from the Western world, thanks to improved living standards and hygiene,[2] but continues to wreak havoc on young, productive lives, especially in sub-Saharan Africa and South Asia. While a recent Global Burden of Disease analysis showcased an overall picture of declining RHD incidence worldwide, the lopsidedness of this picture is evident in the high RHD burden still being experienced by several parts of the developing world.[3] Recent estimates suggest that India contributes to one-third of the worldwide RHD burden, accounting for about 3.7 million disability-adjusted life-years and >100,000 deaths every year.[4]


  Breaking the Progression Cycle: Early Identification Top


The traditional “cycle” of RHD progression involves repeated episodes of acute rheumatic fever (ARF), thanks to a high burden of exposure to the pathogenic Group A Streptococcus (GAS) strains due to poor living conditions, overcrowding, and lack of ready access to medical care.[5] This results in progressive valvular damage and established RHD leading to heart failure.[6] In advanced stages, surgical valve replacement is the only option, for which expertise is limited in underdeveloped nations and is also out of financial reach for many afflicted with the disease. Even among those who are able to undergo surgery, valve replacement comes with its own problems, often consigning young individuals to a lifetime of medical visits, morbidity, and poor quality of life. These issues are especially poignantly brought home when the disease affects women of childbearing age.[7] Theoretically, there is a straightforward way to prevent RHD through the use of easily available, low-cost antibiotic prophylaxis which can prevent disease progression by eliminating repeated GAS infections. However, the problem is, it is often too late by the time the patient comes to medical attention, with significant valve damage already having occurred. Indeed, a majority of patients presenting with RHD do not have a preceding history of symptomatic ARF and there is a large difference between the incidence of RHD and ARF in endemic areas, implying that a good proportion of rheumatic carditis occurs at a subclinical level.[8],[9]

Can we break this usual cycle? Is RHD reversible if identified early enough?

A seminal study carried out in 2007 demonstrated that echocardiography can detect silent RHD, with the incidence being several-fold higher than that detected by clinical auscultation alone.[10] Similarly, a large cross-sectional survey from India showed echocardiographically detected RHD to be twenty times higher compared to clinical detection.[11] Other studies have since confirmed this, giving rise to the concept of subclinical RHD, wherein there are echocardiographic valve abnormalities without clinical symptoms or signs.[12],[13],[14] Logically, this represents an earlier stage in RHD pathogenesis and thus an opportunity to intervene earlier to enable reversal of the disease by timely antibiotic prophylaxis. What needs to be done to translate this concept from the research arena to public health policy?


  Subclinical Rheumatic Heart Disease: What Are the Issues? Top


Consistency of diagnosis

Few important issues emerge when considering the overall aim of identifying subclinical RHD. Firstly, echocardiographic diagnosis of subclinical disease needs to be standardized. Even small variations in definitions can lead to large changes in estimated disease prevalence,[15] which in turn renders meaningful follow-up and assessment of outcomes difficult. With this in mind, the World Heart Federation (WHF), an international expert group, proposed consensus criteria for the diagnosis of subclinical RHD which has been shown to have good intra- and inter-rater reliability.[16] However, while this tries to achieve consistency of definitions worldwide, whether these represent the best possible criteria is unclear, given the lack of a diagnostic gold standard. This uncertainty is evident to some extent in the WHF criteria itself, where echocardiographic diagnosis is categorized into “definite” and “borderline” RHD [Table 1] from Remenyi et al,[16] which is a reflection of the lack of clarity on where to draw the line between normal variation versus mild valve abnormality. Others have proposed a scoring system for different valve abnormalities in order to make the diagnosis more objective as opposed to the subjective nature of the WHF criteria.[17] On the other hand, it is also important to avoid excessive complexity which would be a practical hindrance to mass screening. The best compromise needs to be defined by further study.
Table 1: World Heart Federation echocardiographic criteria for the diagnosis of rheumatic heart disease

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Natural history of latent rheumatic heart disease

Another important consideration is understanding the clinical relevance and natural progression of subclinical RHD, especially with regard to borderline disease, so as to better elucidate the need to intervene with antibiotic prophylaxis in different grades of disease. A survey of >6000 schoolchildren in North India showed progression of latent disease in about 4%, while it regressed in 28% and remained status quo in 68%.[11] However, the median follow-up was only about 15 months in this study. Studies with longer follow-up duration have shown a greater risk of progression of about 11%–16%, as well as a greater risk of ARF recurrence in children with borderline RHD.[18],[19],[20] Thus, it appears that with careful follow-up, there is a clear risk of progression in a subset of cases, with therefore a potential role for antibiotic prophylaxis to halt or retard such progression. There is likely to be some heterogeneity as well in the risk of progression and therefore further identifying risk factors associated with greater progression can help refine our approach to target especially those who would maximally benefit from prevention.[21]

Reversing subclinical rheumatic heart disease

The next question is whether institution of antibiotic prophylaxis in subclinical RHD can reverse disease progression. While one observational study from Africa failed to show any association between adherence to penicillin prophylaxis and disease regression,[22] another recent study from India suggested reversal of lesions even with short duration of prophylaxis.[14] Contrarily, two other studies showed penicillin prophylaxis to be paradoxically associated with a greater risk of disease progression.[19],[21] Observational data, however, have inherent limitations, and unknown confounding factors or selection bias in who gets penicillin prophylaxis (with more advanced disease more likely to be recommended prophylaxis) could lead to spurious results. Disease regression related to prophylaxis cannot be readily differentiated from spontaneous regression and adherence to prophylaxis is also difficult to ascertain in observational designs. Ideally, properly conducted randomized trials with meticulous follow-up are needed to accurately answer this important question. Early results show promise in this regard. A recently completed large cluster-randomized trial in Nepal followed up close to 4000 schoolchildren, comparing a strategy of echocardiographic screening and penicillin prophylaxis with a “control” approach of no screening. After a median follow-up of about 4 years, a significant reduction in definite or borderline RHD was demonstrated in the experimental arm, suggesting that timely institution of antibiotic prophylaxis for subclinical RHD has the potential to prevent progression and reduce disease burden over time.[23] The ongoing GwokO Adunu pa Lutino (GOAL) trial aims to recruit about 1000 children to determine the efficacy of penicillin prophylaxis in retarding/reversing latent RHD in a rigorously conducted randomized control trial.[24]


  Hurdles to Reversing Rheumatic Heart Disease Top


Large-scale screening

In carrying out large-scale screening at a community level, it would be practically impossible to have adequate number of trained cardiologists to perform echocardiography. Hence, performance of focused echocardiography in the field by trained personnel such as nurses or technicians is the reasonable alternative. Studies looking at such performance by semi-professionals have shown encouraging results with reasonable sensitivity and specificity of diagnosis.[25],[26] Related to that, some simplification of echocardiographic criteria may be desirable so that nonexperts can do the job with limited and focused training.[25],[27] However, this would be likely to come at the expense of some compromise in diagnostic accuracy. With the availability of handheld/pocket echo machines and the possibility of exporting images through smartphones, on-site performance by trained personnel and remote diagnosis by experts may be a promising approach in the near future.[28],[29]

Availability of equipment, logistical issues such as transportation to remote areas, electricity for machines, etc., will be some other major challenges to overcome in performing systematic echocardiographic screening. This will need concerted efforts from local governments and public health organizations in unison with interested nongovernmental agencies.

Implementing antibiotic prophylaxis

Institution and compliance with antibiotic prophylaxis for subjects with latent RHD will be crucial to the success of RHD eradication efforts. Although the use of benzathine penicillin once in 3 weeks obviates the need to take daily tablets, studies have still demonstrated poor compliance related to the painful nature of the injection, lack of education/awareness, and cost issues.[30],[31] Thus, for any RHD control program to succeed, screening and antibiotic prophylaxis have to go hand in hand with intensive public education and awareness campaigns.[32] Indeed, the success of pediatric immunization programs in India through the optimal use of mass media and messages through community influencers could be a useful model in this regard.[33]

A need for a unified and multidimensional effort

Large-scale screening and delivery of antibiotic prophylaxis are mammoth undertakings. There is also a need for further dedicated research in the field to address existing knowledge gaps with regard to early RHD, its natural history, and its potential reversibility. These efforts require substantial investments in RHD control programs. Although RHD causes morbidity and mortality on par with diseases such as tuberculosis and HIV, it remains relatively neglected and underfunded.[34] Thus, there is a great need for global awareness and advocacy for RHD which has largely disappeared from the Western world and hence from their attention as well.


  Conclusion Top


While aiming to reverse early RHD is a worthwhile pursuit, complete eradication of RHD is indeed possible and should be the ultimate goal. For this, one needs to strike at the roots of this disease and disrupt the conditions leading to high GAS infection burden. In the final analysis, RHD is a disease of societal inequity. The sharp global heterogeneities in RHD burden are a stark reminder of poverty, inadequate living conditions, and failure of health-care delivery to the most disadvantaged in the society, which should no longer be acceptable.[35] It is time to launch sustained, multipronged efforts combining screening and prophylaxis with public education, awareness, and improvement of living standards in order to have hope of eradicating this devastating disease in the near future.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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