Poor Adherence to Secondary Prophylaxis is Associated with More Severe Rheumatic Valve in Pediatric Patients: A Cross-Sectional Study

Taufieq Ridlo Makhmud, Mohammad Saifur Rohman, Renny Suwarniaty, Djanggan Sargowo, Faris Wahyu Nugroho, Annisa Hasanah, Bambang Kusbandono, Citra Tarannita, Ratih Kusuma Wardani, Sasmojo Widito, Heny Martini


Background : Rheumatic heart disease (RHD) contributed to a large number of proportion amoung cardiovascular problems in developing county, especially Indonesia. Secondary prophylaxis method using intramuscular injection of Benzathin Penicillin-G (BPG) has been known as the most effective strategy in the prevention of RHD. However, whether this prevention method also resulting in prevention of disease severity in Indonesian patients remained to be examined.

Objectives : This study aimed to assess the difference of rheumatic valve severity in Indonesian pediatric patients between adequate and poor adherence to secondary prophylaxis by using intramuscular BPG injection.

Methods : This cross-sectional study was conducted at Pediatric Cardiology Department of Saiful Anwar General Hospital from November 2018 to June 2019. Patients with documented history of RHD were included. Frequency of intramuscular BPG injection during the last one year was recorded. Adherence was measured using the proportion of days covered (PDC) and adequate adherence was defined as PDC ≥0.90. The severity of RHD was assessed based on the severity of the mitral and / or aortic valve using echocardiography. Bivariate analysis and multivariate logistic regression analysis was used to identify characteristics associated with rheumatic valve severity.

Results : A significant difference of rheumatic mitral and/or aortic valve severity was observed between adequate adherence compared to poor adherence group (p = 0.016). Rheumatic mitral and/or aortic valve were found to be more severe in patients who has one or more episode of ARF recurrence (p = 0.003). Multivariate logistic regression analysis demonstrated that adherence to secondary prophylaxis within the last 1 year has the strongest influence on the severity of rheumatic mitral and/or aortic valve (p = 0.049; OR 7.20).

Conclusion : The adherence to secondary prophylaxis has the strongest related the rheumatic valve severity compared to other factors.


rheumatic heart disease; secondary prophylaxis; adherence; echocardiography; pediatric

Full Text:



Marijon E., Mirabel M., Celermajer D.S., Jouven X. Rheumatic Heart Disease. Lancet. 2012; 379: 953–64

Siregar AA. Demam rematik dan penyakit jantung rematik, permasalahan Indonesia. Inauguration Speech of Professor Position at the Faculty of Medicine, University of North Sumatra, Indonesia. 12th April 2008.

Burke R.J. and Chang C. Diagnostic Criteria of Acute Rheumatic Fever. Autoimmunity Reviews. 2014; 13: 503–507

Lawrence J.G., Carapetis J.R., Griffiths K., Edwards K., Condon J.R. 2013. Acute rheumatic fever and rheumatic heart disease: incidence and progression in the Northern Territory of Australia, 1997 to 2010. Circulation. 2013; 128: 492–501.

Culliford-Semmens N., Tilton E., Webb R., et al. Adequate Adherence to Benzathine Penicillin Secondary Prophylaxis Following the Diagnosis of Rheumatic Heart Disease by Echocardiographic Screening. NZMJ. 2017; 130: 50-57

Haran S., Crane N., Kazi S., Axford-Haines L., White A. Effect of Secondary Penicillin Prophylaxis on Valvular Changes in Patients With Rheumatic Heart Disease in Far North Queensland. Aust. J. Rural Health. 2018; 26: 119–125

Lancellotti P., Moura L., Pierard L.A., et al. European Association of Echocardiography Recommendations for Assessment of Valvular Regurgitation. European Journal of Echocardiography. 2010. 11: 307–332

Baumgartner H, Hung J, Bermejo J, et al. Echocardiographic Assessment of Valve Stenosis: EAE/ASE Recommendations for Clinical Practice. Journal of the American Society of Echocardiography. 2009; 2(1): 1-16

Carapetis J., Brown A., Maguire G., et al. 2012. The Australian Guideline for Prevention, Diagnosis and Management of Acute Rheumatic Fever and Rheumatic Heart Disease, 2nd edition.

Camara E.J.N., dos Santos J.M., Silva L.S.A., et al. Rheumatic Fever Recurrence: Risk Factors and Clinical Characteristics. Clinical Trials and Regulatory Science in Cardiology. 2016; 19: 5–8

Kementrian Kesehatan RI. 2011. Buku Saku mengenai Keputusan Menteri Kesehatan Republik Indonesia Nomer 1995/Menkes/SK/XII/2010 tentang Standar Antropometri Penilaian Status Gizi Anak.

Gasse B, Baroux N, Rouchon B, et al. Determinants Of Poor Adherence To Secondary Antibiotic Prophylaxis For Rheumatic Fever Recurrence On Lifou, New Caledonia: A Retrospective Cohort Study. BMC Public Health. 2013; 13:131.

Rahmawaty N.K., Iskandar B., Albar H., et al. 2012. Faktor Risiko Serangan Berulang Demam Rematik/Penyakit Jantung Rematik. Sari Pediatri. 14(3): 179-84

Rémond M.G.W., Coyle M.E., Mills J.E., et al. Approaches to Improving Adherence to Secondary Prophylaxis for Rheumatic Fever and Rheumatic Heart Disease. Cardiology in Review. 2016; 24: 94–98

Stewart T., McDonald R., Currie B. Acute rheumatic fever: Adherence to secondary prophylaxis and follow up of Indigenous patients in the Katherine region of the Northern Territory. Aust. J. Rural Health. 2007; 15: 234–240

WHO program for the prevention of rheumatic fever / rheumatic heart disease in 16 developing countries: report from phase 1 (1986–90). Bulletin of the World Health Organ 1992; 70: 213–218.

Saxena A., Mehta A., Ramakrishnan S. 2015. Adherence to Benzathine Penicillin in Children With Rheumatic Fever/ Rheumatic Heart Disease: Results from an Indian Pediatric RHD Registry. JACC. 65 (10S)

Atatoa-Carr P., Lennon D., Wilson N. Rheumatic Fever Diagnosis, Management, and Secondary Prevention: A New Zealand Guideline. NZMJ. 2008; 121: 59-69

Soliman O.I.I., Anwar A.M., Metawei A.K., et al. New Scores for the Assessment of Mitral Stenosis Using Real-Time Three-Dimensional Echocardiography. Curr Cardiovasc Imaging Rep. 2011; 4: 370-377

Aloui S, Wiem Zidi W, Ouali S, et al. Association Of Matrix Metalloproteinase-3 and Endogenous Inhibitors With Inflammatory Markers In Mitral Valve Disease And Calcification. Molecular Biology Reports. 2018; 45: 2135–2143

Mehta A, Saxena S, Juneja R, et al. Characteristics and Outcomes of Indian Children Enrolled in a Rheumatic Heart Disease Registry. International Journal of Cardiology. 2016; 222: 1136–1140.

Remenyi B., Wilson N., Stirling J., Ferreira B., Kado J., Kumar K., et al. World Heart Federation Criteria for Echocardiographic Diagnosis of Rheumatic Heart Disease, an Evidence-Based Guideline. Nat. Rev. Cardiol. 2012; 9: 297–309.

DOI: https://doi.org/10.21776/ub.hsj.2020.001.01.4


  • There are currently no refbacks.

Copyright (c) 2020 Heart Science Journal

License URL: https://creativecommons.org/licenses/by/4.0/