McCarter, Longenecker, Jacobs, Jiang, Okello, Aliku, Dewyer, Tenywa, Mirembe, Scheel, Namuyonga, Lubega, Mirabel, Lwabi, Sable, Beaton
Background -Screening echocardiography (echo) has emerged as a potentially powerful tool for early diagnosis of rheumatic heart disease (RHD). The utility of screening echo hinges on the rate of RHD progression and the ability of penicillin prophylaxis to improve outcome. We report the longitudinal outcomes of a cohort of children with latent RHD and identify risk factors for unfavorable outcomes. Methods -This was a prospective natural history study conducted under the Ugandan RHD registry. Children with latent RHD and ≥1 year of follow-up were included. All echos were re-reviewed by experts (2012 WHF criteria) for inclusion and evidence of change. Bi- and multi- variable logistic regression, Kaplan-Meier analysis, as well as Cox proportional hazard models were developed to search for risk factors for unfavorable outcome and compare progression-free survival between those treated and not treated with penicillin. Propensity and other matching methods with sensitivity analysis were implemented for the evaluation of the penicillin effect. Results -Blinded review confirmed 227 cases of latent RHD: 164 borderline and 63 definite (42 mild, 21 moderate/severe). Median age at diagnosis was 12 years and median follow-up was 2.3 years (IQR 2.0-2.9). Penicillin prophylaxis was prescribed in 49.3% with overall adherence of 84.7%. Of children with moderate/severe definite RHD, 47.6% had echo progression (including 2 deaths), and 9.5% echo regression. Children with mild definite and borderline RHD showed 26% and 9.8% echo progression and 45.2% and 46.3% echo improvement respectively. Of those with mild definite RHD or borderline RHD, more advanced disease category, younger age, and morphological mitral valve features were risk factors for an unfavorable outcome. Conclusions -Latent RHD is a heterogeneous diagnosis with variable disease outcomes. Children with moderate to severe latent RHD have poor outcomes. Children with both borderline and mild definite RHD are at substantial risk of progression. While long-term outcome remains unclear, the initial change in latent RHD may be evident during the first 1-2 years following diagnosis. Natural history data is inherently limited and a randomized clinical trial is needed to definitively determine the impact of penicillin prophylaxis on the trajectory of latent RHD.
