Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study)

Dear Editor, We thank Dr. M. Bhaya and colleagues for the comments on our manuscript. There are at least three questions that are directed to REMEDY in the commentary. The first relates to the diagnostic criteria that were used in the study. REMEDY is a study of patients with symptoms and signs of rheumatic heart disease and echocardiographic confirmation of chronic rheumatic carditis based on the WHO criteria (1). The second point relates to the age distribution of patients enrolled in the study, which was consistent with the well-known observation that rheumatic heart disease is the commonest acquired cardiac condition of childhood and early adulthood in developing countries (2). Finally, we agree with Dr. Bhana that the cases entered into REMEDY reflect the tip of the iceberg in terms of the overall burden of the disease in the community. The evaluation of the prevalence of rheumatic heart disease requires community-based studies, such as the surveillance studies of school-children that we have recently completed in Ethiopia and South Africa (3). References 1. WHO Technical Report Series. Rheumatic fever and rheumatic heart disease: Report of a who expert panel, Geneva 29 October -1 November 2001. Geneva: WHO; 2004. 2. Remenyi B, Carapetis J, Wyber R, Taubert K, Mayosi BM. Position statement of the world heart federation on the prevention and control of rheumatic heart disease. Nat Rev Cardiol. 2013;10:284-292 3. Engel ME, Haileamlak A, Zuhlke L, Lemmer CE, Nkepu S, Van de Wall M, Daniel W, Shung King M, Mayosi BM. Prevalence of rheumatic heart disease in 4720 asymptomatic scholars from South Africa and Ethiopia. Heart. 2015;in press

We thank Bhaya and colleagues for their interest in our article. The authors comment that there were “more young cases…recruited (from) developing countries” and we did not explain this difference in average age between country groups. In response, we would like to reiterate that REMEDY was a hospital-based registry and importantly, not an all-comer’s one at that. The age distribution among countries depended, among other factors, on the type of hospitals that chose to participate (adult or pediatric). Given this study design it would have been inappropriate for us to have drawn any firm conclusions regarding the age distribution of patients across country groups. In any case, it is well known that as countries become more affluent, the average age of patients with rheumatic heart disease increases, and this data predates the studies on echocardiographic screening. Moreover, there is a paucity of data on the prognostic significance of the predominantly trivial/mild valve disease detected on routine echocardiographic screening of populations. Crucially, there is no robust data on the effect of secondary prophylaxis on progression to symptomatic disease. Given this scenario, it would be imprudent to suggest that (massive amounts of) money and resources be allocated to performing echocardiographic screening of the population in low and lower-middle income countries. Professor Ganesan Karthikeyan, MBBS, MD, DM, MSc

We want to comment upon the fact that more young cases were recruited at centers in the developing countries should be to some extent considered a result of the lack of infrastructure to diagnose the existing cases. Apart from when the patient is experiencing a recurrence of rheumatic fever, the absence of a characteristic symptoms for early stages of rheumatic heart disease makes clinical diagnosis difficult. In resource poor areas, the school age children and young adults are not routinely screened by echocardiography and an occasional case with joint pain is referred for echocardiographic assessment. During this assessment, if the case is not diagnosed as definite rheumatic heart disease, some minor evidence suggestive of rheumatic etiology is likely to be ignored and the patient is not followed up. Consequently, in resource poor areas two out of three cases of rheumatic heart disease do not report any history of rheumatic fever/heart disease (1) and the rheumatic heart disease burden remains high. (2) An observant echocardiography expert shall find many cases in the right epidemiological settings like poor population, lack of healthcare services, and lack of proper treatment of streptococcal sore throats if echocardiographic assessment is routinely done. A diagnostic approach (assessing only symptomatic cases) identifies only the tip of the iceberg. If a registry is on, then the systemic efficiency of healthcare system for diagnostic screening increases and many more cases in younger age groups are reported. These cases in normal circumstances are ignored as guidelines for intervention for these cases exist but logistic pathways and infrastructure capacity to screen the patients for such cases is not existing. To have a control of the rheumatic heart disease burden the intervention should precede the stage when valve damage has occurred. This intervention point largely corresponds to the asymptomatic or minimally symptomatic phase of the probable rheumatic heart disease. Diagnostic criteria for early asymptomatic or minimally symptomatic stages of rheumatic heart disease are ready for trial but how to use these criteria in clinical practice remains the moot question. (3) The "REMEDY" study probes the problem and identifies variable clustering in the different age groups across different areas of world but no hypothesis is aired to enable the quantification of the problem of rheumatic heart disease either at individual level or at population level. We have reported a diagnostic score earlier this year (4), which is potentially able of quantitative assessment of rheumatic heart disease for a case. As every undiagnosed case (criteria not met but suspicion is there) also receives a quantitative score, the community burden of health problem can be potentially assessed. With the collected data for "REMEDY" there is need to quantify the community burden of health problem due to rheumatic heart disease across the world. 1) World Health Organization (2004). Rheumatic fever and rheumatic heart disease: report of WHO expert Consultation, WHO Technical Report Series 923, World Health Organization, Geneva, Switzerland 2) M.Bhaya, S Panwar, R. Beniwal, RB Panwar. High Prevalence of Rheumatic Heart Disease Detected by Echocardiography in School Children. ECHOCARDIOGRAPHY: A Jrnl. of CV Ultrasound & Allied Tech 2010; 27:448-453 3) M Bhaya, R Beniwal, S Panwar and RB Panwar. Two years of follow up validates the echocardiographic criteria for the diagnosis and screening of rheumatic heart disease in asymptomatic populations. Echocardiography: A Jrnl. of CV Ultrasound & Allied Tech 2011; 28:929-933 4) Beniwal, Rajesh Bhaya, Maeesha Panwar, Raja Baba Panwar, Sadiak Singh, Aryak et al. Diagnostic Criteria in Rheumatic Heart Disease. Global Heart , Volume 10 , Issue 1 , 81 – 82, March 2015