Andrea Beaton

Echocardiography Screening for Rheumatic Heart Disease in Ugandan Schoolchildren

Background— Historically, sub-Saharan Africa has had the highest prevalence rates of clinically detected rheumatic heart disease (RHD). Echocardiography-based screening improves detection of RHD in endemic regions. The newest screening guidelines (2006 World Health Organization/National Institutes of Health) have been tested across India and the Pacific Islands, but application in sub-Saharan Africa has, thus far, been limited to Mozambique. We used these guidelines to determine RHD prevalence in a large cohort of Ugandan school children, to identify risk factors for occult disease, and to assess the value of laboratory testing. Methods and Results— Auscultation and portable echocardiography were used to screen randomly selected schoolchildren, 5 to 16 years of age, in Kampala, Uganda. Disease likelihood was defined as definite, probable, or possible in accordance with the 2006 National Institutes of Health/World Health Organization guidelines. Ninety-seven percent of eligible students received screening (4869 of 5006). Among them, 130 children (2.7%) had abnormal screening echocardiograms. Of those 130, secondary evaluation showed 72 (55.4%) with possible, probable, or definite RHD; 18 (13.8%) with congenital heart disease; and 40 (30.8%) with no disease. Echocardiography detected 3 times as many cases of RHD as auscultation: 72 (1.5%) versus 23 (0.5%; P<0.001). Children with RHD were older (10.1 versus 9.3 years; P=0.002). Most cases (98%) involved only the mitral valve. Lower socioeconomic groups had more RHD (2.7% versus 1.4%; P=0.036) and more advanced disease (64% versus 26%; P<0.001). Antistreptolysin O titers were elevated in children with definite RHD. Conclusions— This is one of the largest single-country childhood RHD prevalence studies and the first to be conducted in sub-Saharan Africa. Our data support inclusion of echocardiography in screening protocols, even in the most resource-constrained settings, and identify lower socioeconomic groups as most vulnerable. Longitudinal follow-up of children with echocardiographically diagnosed subclinical RHD is needed.

Revision of the Jones Criteria for the Diagnosis of Acute Rheumatic Fever in the Era of Doppler Echocardiography A Scientific Statement From the American Heart Association

Background— Acute rheumatic fever remains a serious healthcare concern for the majority of the world’s population despite its decline in incidence in Europe and North America. The goal of this statement was to review the historic Jones criteria used to diagnose acute rheumatic fever in the context of the current epidemiology of the disease and to update those criteria to also take into account recent evidence supporting the use of Doppler echocardiography in the diagnosis of carditis as a major manifestation of acute rheumatic fever. Methods and Results— To achieve this goal, the American Heart Association’s Council on Cardiovascular Disease in the Young and its Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee organized a writing group to comprehensively review and evaluate the impact of population-specific differences in acute rheumatic fever presentation and changes in presentation that can result from the now worldwide availability of nonsteroidal anti-inflammatory drugs. In addition, a methodological assessment of the numerous published studies that support the use of Doppler echocardiography as a means to diagnose cardiac involvement in acute rheumatic fever, even when overt clinical findings are not apparent, was undertaken to determine the evidence basis for defining subclinical carditis and including it as a major criterion of the Jones criteria. This effort has resulted in the first substantial revision to the Jones criteria by the American Heart Association since 1992 and the first application of the Classification of Recommendations and Levels of Evidence categories developed by the American College of Cardiology/American Heart Association to the Jones criteria. Conclusions— This revision of the Jones criteria now brings them into closer alignment with other international guidelines for the diagnosis of acute rheumatic fever by defining high-risk populations, recognizing variability in clinical presentation in these high-risk populations, and including Doppler echocardiography as a tool to diagnose cardiac involvement.

Global, Regional, and National Burden of Rheumatic Heart Disease, 1990-2015.

BACKGROUND Rheumatic heart disease remains an important preventable cause of cardiovascular death and disability, particularly in low‐income and middle‐income countries. We estimated global, regional, and national trends in the prevalence of and mortality due to rheumatic heart disease as part of the 2015 Global Burden of Disease study. METHODS We systematically reviewed data on fatal and nonfatal rheumatic heart disease for the period from 1990 through 2015. Two Global Burden of Disease analytic tools, the Cause of Death Ensemble model and DisMod‐MR 2.1, were used to produce estimates of mortality and prevalence, including estimates of uncertainty. RESULTS We estimated that there were 319,400 (95% uncertainty interval, 297,300 to 337,300) deaths due to rheumatic heart disease in 2015. Global age‐standardized mortality due to rheumatic heart disease decreased by 47.8% (95% uncertainty interval, 44.7 to 50.9) from 1990 to 2015, but large differences were observed across regions. In 2015, the highest age‐standardized mortality due to and prevalence of rheumatic heart disease were observed in Oceania, South Asia, and central sub‐Saharan Africa. We estimated that in 2015 there were 33.4 million (95% uncertainty interval, 29.7 million to 43.1 million) cases of rheumatic heart disease and 10.5 million (95% uncertainty interval, 9.6 million to 11.5 million) disability‐adjusted life‐years due to rheumatic heart disease globally. CONCLUSIONS We estimated the global disease prevalence of and mortality due to rheumatic heart disease over a 25‐year period. The health‐related burden of rheumatic heart disease has declined worldwide, but high rates of disease persist in some of the poorest regions in the world. (Funded by the Bill and Melinda Gates Foundation and the Medtronic Foundation.)

Acute rheumatic fever and rheumatic heart disease.

Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. The long-term damage to cardiac valves caused by ARF, which can result from a single severe episode or from multiple recurrent episodes of the illness, is known as rheumatic heart disease (RHD) and is a notable cause of morbidity and mortality in resource-poor settings around the world. Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. Recent advances — including the use of echocardiographic diagnosis in those with ARF and in screening for early detection of RHD, progress in developing group A streptococcal vaccines and an increased focus on the lived experience of those with RHD and the need to improve quality of life — give cause for optimism that progress will be made in coming years against this neglected disease that affects populations around the world, but is a particular issue for those living in poverty.

The utility of handheld echocardiography for early rheumatic heart disease diagnosis: A field study

AIMS The World Heart Federation (WHF) guidelines for rheumatic heart disease (RHD) are designed for a standard portable echocardiography (STAND) machine. A recent study in a tertiary care centre demonstrated that they also had good sensitivity and specificity when modified for use with handheld echocardiography (HAND). Our study aimed to evaluate the performance of HAND for early RHD diagnosis in the setting of a large-scale field screening. METHODS AND RESULTS STAND was performed in 4773 children in Gulu, Uganda, with 10% randomly assigned to also undergo HAND. Additionally, any child with mitral or aortic regurgitation also underwent HAND. Studies were performed by experienced echocardiographers and blindly reviewed by cardiologists using 2012 WHF criteria, which were modified slightly for HAND--due to the lack of spectral Doppler capability. Paired echocardiograms were performed in 1420 children (mean age 10.8 and 53% female), resulting in 1234 children who were normal, 133 who met criteria for borderline RHD, 47 who met criteria for definite RHD, and 6 who had other diagnoses. HAND had good sensitivity and specificity for RHD detection (78.9 and 87.2%, respectively), but was most sensitive for definite RHD (97.9%). Inter- and intra-reviewer agreement ranged between 66-83 and 71.4-94.1%, respectively. CONCLUSIONS HAND has good sensitivity and specificity for diagnosis of early RHD, performing best for definite RHD. Protocols for RHD detection utilizing HAND will need to include confirmation by STAND to avoid over-diagnosis. Strategies that evaluate simplified screening protocols and training of non-physicians hold promise for more wide spread deployment of HAND-based protocols.

Relation of Coarctation of the Aorta to the Occurrence of Ascending Aortic Dilation in Children and Young Adults With Bicuspid Aortic Valves

Children with bicuspid aortic valve (BAV) have aortic dilation that is present and progressive from birth irrespective of the functional state of the valve. There are no published data comparing aortic dilation in children with BAV with and without aortic coarctation (CoA). The objectives of this study were to (1) compare differences in aortic dimensions and rates of dilation between children with isolated BAV with those of children with BAV and CoA and (2) identify risk factors for the development of aortic dilation. Patients with BAV with CoA (group A) and without CoA (group B) were identified from our echocardiographic database (1993 to 2006). Aortic measurements at 4 levels were obtained, and z scores were compared. Criteria for exclusion were severe aortic regurgitation/stenosis, previous aortic valvuloplasty, complex left-sided cardiac disease, ventricular septal defects, and Turner, Noonan, Williams, and Marfan syndromes. There were 600 echocardiograms in 247 patients. Group A had 192 echocardiograms in 53 patients (median age 11.3 years; range 0 to 30; median follow-up 7 years), and group B had 382 in 194 patients (median age 8.7 years; range 0 to 29; median follow-up 4 years). Group B had significantly greater ascending aorta dimensions (p<0.05) and significantly faster rates of aortic dilation (p<0.0001). The ascending aorta in patients with BAV and CoA did not dilate to the same degree as in patients with isolated BAV. In conclusion, valve morphologic characteristics and function and age at CoA repair had none to minimal impact on aortic dimensions.

Handheld echocardiographic screening for rheumatic heart disease by non-experts

Objectives Handheld echocardiography (HAND) has good sensitivity and specificity for rheumatic heart disease (RHD) when performed by cardiologists. However, physician shortages in RHD-endemic areas demand less-skilled users to make RHD screening practical. We examine nurse performance and interpretation of HAND using a simplified approach for RHD screening. Methods Two nurses received training on HAND and a simplified screening approach. Consented students at two schools in Uganda were eligible for participation. A simplified approach (HAND performed and interpreted by a non-expert) was compared with the reference standard (standard portable echocardiography, performed and interpreted by experts according to the 2012 World Heart Federation guidelines). Reasons for false-positive and false-negative HAND studies were identified. Results A total of 1002 children were consented, with 956 (11.1 years, 41.8% male) having complete data for review. Diagnoses included: 913 (95.5%) children were classified normal, 32 (3.3%) borderline RHD and 11 (1.2%) definite RHD. The simplified approach had a sensitivity of 74.4% (58.8% to 86.5%) and a specificity of 78.8% (76.0% to 81.4%) for any RHD (borderline and definite). Sensitivity improved to 90.9% (58.7% to 98.5%) for definite RHD. Identification and measurement of erroneous colour jets was the most common reason for false-positive studies (n=164/194), while missed mitral regurgitation and shorter regurgitant jet lengths with HAND were the most common reasons for false-negative studies (n=10/11). Conclusions Non-expert-led HAND screening programmes offer a potential solution to financial and workforce barriers that limit widespread RHD screening. Nurses trained on HAND using a simplified approach had reasonable sensitivity and specificity for RHD screening. Information on reasons for false-negative and false-positive screening studies should be used to inform future training protocols, which could lead to improved screening performance.

Handheld echocardiography versus auscultation for detection of rheumatic heart disease

BACKGROUND: Rheumatic heart disease (RHD) remains a major public health concern in developing countries, and routine screening has the potential to improve outcomes. Standard portable echocardiography (STAND) is far more sensitive than auscultation for the detection of RHD but remains cost-prohibitive in resource-limited settings. Handheld echocardiography (HAND) is a lower-cost alternative. The purpose of this study was to assess the incremental value of HAND over auscultation to identify RHD. METHODS: RHD screening was completed for schoolchildren in Gulu, Uganda, by using STAND performed by experienced echocardiographers. Any child with mitral or aortic regurgitation or stenosis plus a randomly selected group of children with normal STAND findings underwent HAND and auscultation. STAND and HAND studies were interpreted by 6 experienced cardiologists using the 2012 World Heart Federation criteria. Sensitivity and specificity of HAND and auscultation for the detection of RHD and pathologic mitral or aortic regurgitation were calculated by using STAND as the gold standard. RESULTS: Of 4773 children who underwent screening with STAND, a subgroup of 1317 children underwent HAND and auscultation. Auscultation had uniformly poor sensitivity for the detection of RHD or valve disease. Sensitivity was significantly improved by using HAND compared with auscultation for the detection of definite RHD (97.8% vs 22.2%), borderline or definite RHD (78.4% vs 16.4%), and pathologic aortic insufficiency (81.8% vs 13.6%). CONCLUSIONS: Auscultation alone is a poor screening test for RHD. HAND significantly improves detection of RHD and may be a cost-effective screening strategy for RHD in resource-limited settings.

Simplified Rheumatic Heart Disease Screening Criteria for Handheld Echocardiography

BACKGROUND Using 2012 World Heart Federation criteria, standard portable echocardiography (STAND) reveals a high burden of rheumatic heart disease (RHD) in resource-poor settings, but widespread screening is limited by cost and physician availability. Handheld echocardiography (HAND) may decrease costs, but World Heart Federation criteria are complicated for rapid field screening, particularly for nonphysician screeners. The aim of this study was to determine the best simplified screening strategy for RHD detection using HAND. METHODS In this prospective study, STAND (GE Vivid q or i or Philips CX-50) was performed in five schools in Gulu, Uganda; a random subset plus all children with detectable mitral regurgitation or aortic insufficiency also underwent HAND (GE Vscan). Borderline or definite RHD cases were defined by 2012 World Heart Federation criteria on STAND images, by two experienced readers. HAND studies were reviewed by cardiologists blinded to STAND results. Single and combined HAND parameters were evaluated to determine the simplified screening strategy that maximized sensitivity and specificity for case detection. RESULTS In 1,439 children (mean age, 10.8 ± 2.6 years; 47% male) with HAND and STAND studies, morphologic criteria and the presence of any mitral regurgitation by HAND had poor specificity. The presence of aortic insufficiency was specific but not sensitive. Combined criteria of mitral regurgitation jet length ≥ 1.5 cm or any aortic insufficiency best balanced sensitivity (73.3%) and specificity (82.4%), with excellent sensitivity for definite RHD (97.9%). With a prevalence of 4% and subsequent STAND screening of positive HAND studies, this would reduce STAND studies by 80% from a STAND-based screening strategy. CONCLUSIONS In resource-limited settings, HAND with simplified criteria can detect RHD with good sensitivity and specificity and decrease the need for standard echocardiography. Further study is needed to validate screening by local practitioners and long-term outcomes.

Echocardiographic prevalence of rheumatic heart disease in Brazilian schoolchildren: Data from the PROVAR study

BACKGROUND Accurate estimates of Rheumatic Heart Disease (RHD) burden are needed to justify improved integration of RHD prevention and screening into the public health systems, but data from Latin America are still sparse. OBJECTIVE To determine the prevalence of RHD among socioeconomically disadvantaged youth (5-18years) in Brazil and examine risk factors for the disease. METHODS The PROVAR program utilizes non-expert screeners, telemedicine, and handheld and standard portable echocardiography to conduct echocardiographic screening in socioeconomically disadvantaged schools in Minas Gerais, Brazil. Cardiologists in the US and Brazil provide expert interpretation according to the 2012 World Heart Federation Guidelines. Here we report prevalence data from the first 14months of screening, and examine risk factors for RHD. RESULTS 5996 students were screened across 21 schools. Median age was 11.9 [9.0/15.0] years, 59% females. RHD prevalence was 42/1000 (n=251): 37/1000 borderline (n=221) and 5/1000 definite (n=30). Pathologic mitral regurgitation was observed in 203 (80.9%), pathologic aortic regurgitation in 38 (15.1%), and mixed mitral/aortic valve disease in 10 (4.0%) children. Older children had higher prevalence (50/1000 vs. 28/1000, p<0.001), but no difference was observed between northern (lower resourced) and central areas (34/1000 vs. 44/1000, p=0.31). Females had higher prevalence (48/1000 vs. 35/1000, p=0.016). Age (OR=1.15, 95% CI:1.10-1.21, p<0.001) was the only variable independently associated with RHD findings. CONCLUSIONS RHD continues to be an important and under recognized condition among socioeconomically disadvantaged Brazilian schoolchildren. Our data adds to the compelling case for renewed investment in RHD prevention and early detection in Latin America.