Rheumatic heart disease in Uganda: predictors of morbidity and mortality one year after presentation

Emmy Okello, Chris T Longenecker, Andrea Beaton, Moses R Kamya, Peter Lwabi, Emmy Okello, Chris T Longenecker, Andrea Beaton, Moses R Kamya, Peter Lwabi

Abstract

Background: Rheumatic heart disease (RHD), the long-term consequence of rheumatic fever, accounts for most cardiovascular morbidity and mortality among young adults in developing countries. However, data on contemporary outcomes from resource constrained areas are limited.

Methods: A prospective cohort study of participants aged 5-60 years with established RHD was conducted in Kampala, Uganda, in which clinical exam, echocardiography, electrocardiography (ECG), and laboratory evaluation were done every 3 months and every 4-week benzathine penicillin prophylaxis was prescribed. Participants were followed up for 12 months and outcomes and predictors of morbidity and mortality were assessed using Kaplan Meier curves and Cox proportional hazards models.

Results: Of 449 subjects, 66.8% (300/449) were females, median age was 30 (interquartile range 20). 73.7% (331/449) had atleast one follow up visit. Among these, 35% (116/331) developed decompensated heart failure and, 63.7% (211/331) developed atrial fibrillation. Heart failure was associated with poor penicillin adherence (OR = 3.3, CI 2-5.4, p = 0.001), and left ventricular end diastolic diameter greater than 55 mm (OR = 3.16, CI 1.73-5.76, p = 0.001). Atrial fibrillation was associated with left atrial diameter >40 mm (OR = 7.5, CI 2.4-9.8, p = 0.001). There were 59 deaths with a 1-year mortality rate of 17.8%. Most deaths occurred within the first three months of presentation. Subjects whose average adherence to benzathine penicillin was <80% had significantly greater mortality (31% vs. 9%, log rank p < 0.001). In multivariate analysis, the risk of death among those with poor penicillin adherence was 3.81 times higher than those with better adherence (HR = 3.81, CI 1.92-7.63, p = 0.001). Other predictors of 1 year mortality included heart failure (HR 8.36, CI 3.28-21.31, p = 0.001) and left ventricular end diastolic diameter greater than 55 mm (HR = 1.93, CI 1.07-3.49, p = 0.02).

Conclusion: In this study of RHD in Uganda, morbidity and mortality within 1 year of presentation were higher than in recently published from other low and middle income countries. Suboptimal adherence to benzathine penicillin injections was associated with incident heart failure and mortality over 1 year. Future studies should test interventions to improve adherence among patients with advanced disease who are at the highest risk of mortality.

Keywords: Morbidity; Mortality; Outcomes; Predictors; Rheumatic heart disease; Uganda.

Figures

Fig. 1
Fig. 1
Morbidity During the First Year Following Initial RHD Presentation
Fig. 2
Fig. 2
Kaplan- Meier curve for mortality within one year of initial presentation with rheumatic heart disease
Fig. 3
Fig. 3
Kaplan Meir curves of participant survival stratified by benzathine penicillin adherence (80%)

References

    1. Lozano MN, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095–2128. doi: 10.1016/S0140-6736(12)61728-0.
    1. Roberts KCS, Steer A, Reményi B, Carapetis J. Screening for rheumatic heart disease: current approaches and controversies. Nat Rev Cardiol. 2013;10(1):49–58. doi: 10.1038/nrcardio.2012.157.
    1. Wood H, Feinstein AR, Taranta A, Epstein JA, Simpson R. Rheumatic fever in children and adolescents: a long-term epidemiologic study of subsequent prophylaxis, streptococcal infections, and clinical sequelae: III. Comparative effectiveness of three prophylaxis regiments in preventing streptococcal infection and rheumatic recurrences. Ann Intern Med. 1964;60:31–46. doi: 10.7326/0003-4819-60-2-31.
    1. Bland E, Jones T. Rheumatic fever and rheumatic heart disease. A twenty-year report on 1,000 patients followed since childhood. Circulation. 1951;4:836–843. doi: 10.1161/01.CIR.4.6.836.
    1. Tompkins DG, Boxerbaum B, Liebman J. Long-term prognosis of rheumatic fever patients receiving regular intramuscular benzathine penicillin. Circulation. 1972;1972:543–551. doi: 10.1161/01.CIR.45.3.543.
    1. Kayima J, Mungoma M, Mondo C, Freers J. The Changing Pattern of Cardiac disease in Africa: The Ugandan Experience. Cardiovas J Afr. 2011;22(3):S9.
    1. Okello E, Zhang W, Musoke C, Aliku T, Kakande B, et al. Cardiovascular complications in newly diagnosed rheumatic heart disease patients at Mulago Hospital, Uganda. Cardiovas J Afr. 2013;24(3):80–85. doi: 10.5830/CVJA-2013-004.
    1. Majeed H, Batnager S, Yousof AM, Khuffash F, Yusuf AR. Acute rheumatic fever and the evolution of rheumatic heart disease: a prospective 12 year follow-up report. J Clin Epidemiol. 1992;45:871–875. doi: 10.1016/0895-4356(92)90070-4.
    1. Meira ZMA, Goulart EMA, Colosimo EA, Mota CCC. Long term follow up of rheumatic fever and predictors of severe rheumatic valvar disease in Brazilian children and adolescents. Heart. 2005;91:1019–1022. doi: 10.1136/hrt.2004.042762.
    1. Zühlke L, Karthikeyan G, Engel ME, Rangarajan S, Mackie P, Cupido B, et al. Clinical Outcomes in 3343 Children and Adults with Rheumatic Heart Disease from 14 Low and Middle Income Countries: 2-Year Follow-up of the Global Rheumatic Heart Disease Registry (the REMEDY study) Circulation. 2016;134:1456–1466. doi: 10.1161/CIRCULATIONAHA.116.024769.
    1. Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, et al. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. J Am Soc Echocardiogr. 2009;1:1–23.
    1. Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr. 2003;16(7):777–802. doi: 10.1016/S0894-7317(03)00335-3.
    1. Steer AC, Vidmar S, Ritika R, Kado J, Batzloff M, et al. Normal Ranges of Streptococcal Antibody Titers Are Similar Whether Streptococci Are Endemic to the Setting or Not. Clin Vaccine Immunol. 2009;16(2):172–175. doi: 10.1128/CVI.00291-08.
    1. Prineas RJ, Rischard S, Blackburn H. The Minnesota Code Manual of electrocardiographic Findings: Standards and Procedures for Measurement and Classification. Boston: John Wright; 1982.
    1. McKee P, Castelli WE, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med. 1971;285:1441–1446. doi: 10.1056/NEJM197112232852601.
    1. Carapetis JP, Paar J, Cherian T. Standardization of epidemiologic protocols for surveillance of post-streptococcal sequelae: acute rheumatic fever, rheumatic heart disease and acute post-streptococcal glomerulonephritis. National Institute of Allergy and Infectious Diseases. 2006. .
    1. Mylonakis E, Calderwood S. Infective endocarditis in adults. N Engl J Med. 2001;345:1318–1330. doi: 10.1056/NEJMra010082.
    1. Kelsey KL, Whittemore AS, Evans AS, Thompson DW. Methods in Observational Epidemiology. 2. USA: Oxford University Press; 1996.
    1. Musoke C, Mondo C, Okello E, Zhang WZ, Kakande B, et al. Benzathine Penicillin Adherence for Secondary Prophylaxis among Patients Affected with Rheumatic Heart Disease Attending Mulago Hospital. Cardiovasc J Afr. 2013;24(4):124–129. doi: 10.5830/CVJA-2013-022.
    1. Günther G, Asmera J, Parry E. Death from rheumatic heart disease in rural Ethiopia. Lancet. 2006;367:391. doi: 10.1016/S0140-6736(06)68128-2.
    1. Lauritsen JM, Bruus M. A comprehensive tool for validated entry and documentation of data. Odense: The EpiData Association; 2000–2008. .
    1. Lawrence JG, Carapetis J, Griffiths K, Edwards K, Condon JR. Acute rheumatic Fever and rheumatic heart disease: incidence and progression in the northern territory of australia, 1997 to 2010. Circulation. 2013;5(128):492–501. doi: 10.1161/CIRCULATIONAHA.113.001477.
    1. Zühlke L, Engel M, Karthikeyan G, Rangarajan S, Mackie P, Cupido B, et al. Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study) Eur Heart J. 2015;18(36):1115–1221. doi: 10.1093/eurheartj/ehu449.
    1. WHO Technical Report Series 923 . Rheumatic fever and rheumatic heart disease—Report of a WHO expert consultation, Geneva, Oct 29–Nov 1, 2001. Geneva: World Health Organization; 2004.
    1. Manyemba J, Mayosi BM. Penicillin for secondary prevention of rheumatic fever. Cochrane Database Syst Rev. 2002;3:CD002227.
    1. Gerber MA, Baltimore RS, Eaton CB, Gewitz M, Rowley AH, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation. 2009;11(119):1541–1551. doi: 10.1161/CIRCULATIONAHA.109.191959.

Source: PubMed

3
Prenumerera