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. 2017 Dec 5;136(23):2233-2244.
doi: 10.1161/CIRCULATIONAHA.117.029936. Epub 2017 Sep 27.

Latent Rheumatic Heart Disease: Identifying the Children at Highest Risk of Unfavorable Outcome

Andrea Beaton  1 , Twalib Aliku  2 , Alyssa Dewyer  2 , Marni Jacobs  2 , Jiji Jiang  2 , Chris T Longenecker  2 , Sulaiman Lubega  2 , Robert McCarter  2 , Mariana Mirabel  2 , Grace Mirembe  2 , Judith Namuyonga  2 , Emmy Okello  2 , Amy Scheel  2 , Emmanuel Tenywa  2 , Craig Sable  2 , Peter Lwabi  2
Affiliations

Latent Rheumatic Heart Disease: Identifying the Children at Highest Risk of Unfavorable Outcome

Andrea Beaton et al. Circulation. .

Abstract

Background: Screening echocardiography has emerged as a potentially powerful tool for early diagnosis of rheumatic heart disease (RHD). The utility of screening echocardiography 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 echocardiograms were re-reviewed by experts (2012 World Heart Federation criteria) for inclusion and evidence of change. Bi- and multivariable logistic regression, Kaplan-Meier analysis, and Cox proportional hazards models, as well, 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 (interquartile range, 2.0-2.9). Penicillin prophylaxis was prescribed in 49.3% with overall adherence of 84.7%. Of children with moderate-to-severe definite RHD, 47.6% had echocardiographic progression (including 2 deaths), and 9.5% had echocardiographic regression. Children with mild definite and borderline RHD showed 26% and 9.8% echocardiographic progression and 45.2% and 46.3% echocardiographic 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. Although long-term outcome remains unclear, the initial change in latent RHD may be evident during the first 1 to 2 years following diagnosis. Natural history data are inherently limited, and a randomized clinical trial is needed to definitively determine the impact of penicillin prophylaxis on the trajectory of latent RHD.

Keywords: echocardiography; outcome assessment (health care); pediatrics; rheumatic heart disease; screening.

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Conflict of interest statement

CONFLICTS OF INTEREST DISCLOSURES: None

Figures

Figure 1
Figure 1
Map of Uganda showing the two districts of enrollment.
Figure 2
Figure 2
Flowchart of study entry and classification according to CONSORT recommendations.
Figure 3
Figure 3
RHD Trajectory by Initial Diagnostic Classification (Favorable and Unfavorable outcomes are shown above the bars in solid (favorable) and dashed (unfavorable) bars for Outcome 1 (O1) and Outcome 2 (O2).)
Figure 4
Figure 4
Progression free Survival Stratified by Disease Status
See this image and copyright information in PMC

Comment in

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