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Assessing the risk factors in rheumatic heart disease

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Rheumatic heart disease is caused by untreated throat infections from the streptococcal bacterium. The infections progress into acute rheumatic fever and eventually weaken the valves of the heart.

Rheumatic heart disease (RHD) is the most commonly acquired cardiovascular disease in children and young adults. The devastating condition, which was endemic in the United States before 1950, is now relatively rare in the developed world due to social and economic development and the introduction of penicillin. But, in the developing world RHD remains nearly as common as HIV.

Fortunately, RHD is a cumulative disease and opportunities exist for early intervention. To further explore the utility of early diagnosis and intervention, a research team headed by Children’s National Heart Institute cardiologist Andrea Beaton, M.D., conducted a prospective natural history study of children with latent RHD.

RHD is caused by untreated streptococcal throat infections that progress into acute rheumatic fever (ARF) and eventually weaken the valves of the heart. While initial episodes of ARF occur almost exclusively during childhood, RHD most commonly presents in adolescents and young adults. This latent period between ARF and clinically apparent RHD is an ideal opportunity for early intervention, and screening echocardiography (echo) has emerged as a potentially powerful tool for early detection of RHD.

In their study published in the journal Circulation in September 2017, Dr. Beaton and her colleagues examined echocardiograms from children with latent RHD who were enrolled in the Ugandan National RHD registry. The researchers also developed models to search for risk factors and compare progression-free survival between patients who did and did not receive penicillin.

The team reports that children with moderate-to-severe latent RHD discovered by echo screening have poor outcomes. Children with both borderline and mild definite RHD have better outcomes but remain at substantial risk of progression. The researchers also found that children who are diagnosed at a younger age, and the presence of morphological mitral valve features, generally lead to unfavorable outcomes.

The authors conclude that children with moderate to severe RHD at screening should be considered for treatment as clinically diagnosed RHD, and that children with borderline or mild definite RHD at screening should, at a minimum, be maintained in close clinical follow up.

“It is clear that children found to have the earliest forms of RHD, seen only by echo, are at substantial risk for progression of disease. This study urges us forward to see if we can intervene to stop this progression once children are identified,” says Dr. Beaton.  “We are excited that our next project will be to do just that – a randomized clinical trial in Uganda to determine if penicillin can protect the hearts of children found to have latent RHD.”

Taking telemedicine to heart

For seven years, a Children’s National team has worked on new technologies to blunt the severity of rheumatic heart disease around the world, vastly improving patients’ chances of avoiding serious complications.

Rheumatic heart disease (RHD) is caused by repeated infections from the same bacteria that cause strep throat, which progressively lead to worsening inflammation of the heart’s valves with each successive infection. Over time, these valves thicken with scar tissue and prevent the heart from effectively pumping life-sustaining, oxygenated blood. The devastating condition, which was endemic in the United States before 1950, is now so rare that few outside the medical community have even heard of it. But in the developing world, explains Craig Sable, M.D., director of echocardiography and pediatric cardiology fellowship training and medical director of telemedicine at Children’s National Health System, RHD is nearly as common as HIV.

“RHD is the world’s forgotten disease,” Dr. Sable says. An estimated 32.9 million people worldwide have this condition, most of whom reside in low- to middle-income countries — places that often lack the resources to effectively diagnose and treat it.

Dr. Sable, Andrea Z. Beaton, M.D., and international colleagues plan to overturn this paradigm. For the last seven years, the team has worked on developing new technologies that could blunt the severity of RHD, vastly improving patients’ chances of avoiding its most serious complications.

At the heart of their approach is telemedicine — the use of telecommunications and information technology to provide clinical support for doctors and other care providers who often practice a substantial distance away. Telemedicine already has proven extremely useful within resource-rich countries, such as the United States, according to Dr. Sable. He and Children’s National colleagues have taken advantage of it for years to diagnose and treat pediatric disease from a distance, ranging from diabetes to asthma to autism. In the developing world, he says, it could be a game-changer, offering a chance to equalize healthcare between low- and high-resource settings.

In one ongoing project, a team led by Drs. Sable and Beaton is using telemedicine to screen children for RHD, a critical step to making sure that kids whose hearts already have been damaged receive the antibiotics and follow-up necessary to prevent further injury. After five years of working in Africa, the team recently expanded their project to Brazil, a country riddled with the poverty and overcrowding known to contribute to RHD.

Starting in 2014, the researchers began training four non-physicians, including medical technicians and nurses, to use handheld ultrasound machines to gather the precise series of heart images required for RHD diagnosis. They deployed these healthcare workers to schools in Minas Gerais, the second-most populous state in Brazil, to screen children between the ages of 7 and 18, the population most likely to be affected. With each worker scanning up to 30 children per day at 21 area schools, the researchers eventually amassed nearly 6,000 studies in 2014 and 2015.

Each night, the team on the ground transmitted their data to a cloud server, from which Children’s cardiologists, experts in RHD, and a regional hospital, Universidade Federal de Minas Gerais, accessed and interpreted the images.

“There was almost zero downtime,” Dr. Sable remembers. “The studies were transferred efficiently, they were read efficiently, and the cloud server allowed for easy sharing of information if there was concern about any questionable findings.”

In a study published online on November 4, 2016 in the Journal of Telemedicine and Telecare, Dr. Sable and colleagues reported the project’s success. Together, the team diagnosed latent heart disease in 251 children — about 4.2 percent of the subjects screened — allowing these patients to receive the regular antibiotics necessary to prevent further valve damage, and for those with hearts already badly injured to receive corrective surgery.

The researchers continued to collect data after the manuscript was submitted for publication. The team, which includes Drs. Bruno R. Nascimento, Adriana C. Diamantino, Antonio L.P. Ribeiro and Maria do Carmo P. Nunes, has screened a total of roughly 12,000 Brazilian schoolchildren to date.

Dr. Sable notes there is plenty of room for improvement in the model. For example, he says, the research team has not found a low-bandwidth solution to directly transmit the vast amount of data from each screening in real time, which has caused a slight slowdown of information to the hospital teams. The team eventually hopes to incorporate RHD screenings into annual health exams at local health clinics, sidestepping potential drawbacks of school day screenings.

Overall, being able to diagnose RHD using non-physicians and portable ultrasounds could eventually help Minas Gerais and additional low- to middle-income areas of the world where this disease remains endemic reach the same status as the United States and other resource-heavy countries.

“We’re putting ultrasound technology in the hands of people who otherwise wouldn’t have it,” says Dr. Sable, “and it could have a huge impact on their overall health.”

This work was supported by a grant from the Verizon Foundation and in-kind donations from General Electric and ViTelNet.

Rheumatic heart disease is a family affair

Parasternal long axis echocardiographic still frames in early systole in black and white and color Doppler of RHD-positive index case, sibling, and mother.

Parasternal long axis echocardiographic still frames in early systole in black and white and color Doppler of RHD-positive index case, sibling, and mother.

Siblings of children in Northern Uganda with latent rheumatic heart disease (RHD) are more likely to have the disease and would benefit from targeted echocardiographic screening to detect RHD before it causes permanent damage to their heart valves, according to an unprecedented family screening study.

RHD results from a cascade of health conditions that begin with untreated group A β-hemolytic streptococcal infection. In 3 percent to 6 percent of cases, repeat strep throat can lead to acute rheumatic fever. Almost half of children who experience acute rheumatic fever later develop chronic scarring of the heart valves, RHD.  RHD affects around 33 million people and occurs most commonly in low-resource environments, thriving in conditions of poverty, poor sanitation, and limited primary healthcare. Treating streptococcal infections can prevent a large percentage of children from developing RHD, but these infections are difficult to diagnose in low-resource settings.

Right now, kids with RHD often are not identified until they reach adolescence, when the damage to their heart valves is advanced and severe cardiac symptoms or complications develop. In such countries, cardiac specialists are rare, and intervention at an advanced stage is typically too expensive or unavailable.  Echocardiographic screening can “see” RHD before symptoms develop and allow for earlier, more affordable, and more practical intervention. A team led by Children’s National Health System clinicians and researchers conducted the first-ever family echocardiographic screening study over three months to help identify optimal strategies to pinpoint the families in Northern Uganda at highest RHD risk.

“Echocardiographic screening has the potential to be a powerful public health strategy to lower the burden of RHD around the world,” says Andrea Beaton, M.D., a cardiologist at Children’s National and the study’s senior author. “Finding the 1 percent of vulnerable children who live in regions where RHD is endemic is a challenge. But detecting these silent illnesses would open the possibility of providing these children monthly penicillin shots – which cost pennies and prevent recurrent streptococcal infections, rheumatic fever, and further valve damage.”

The research team leveraged existing school-based screening data in Northern Uganda’s Gulu District and recruited 60 RHD-positive children and matched them with 67 kids attending the same schools who were similar in age and gender but did not have RHD. After screening more than 1,000 parents, guardians, and first-degree family members, they found that children with RHD were 4.5 times as likely to have a sibling who definitely had RHD.

“Definite RHD was more likely to be found in mothers, with 9.3 percent (10/107 screened) having echocardiographic evidence of definite RHD, compared to fathers 0 percent (0/48 screened, p = 0.03), and siblings 3.3 percent (10/300 screened, p = 0.02),” writes lead author Twalib Aliku, School of Medicine, Gulu University, and colleagues. “There was no increased familial, or sibling risk of RHD in the first-degree relatives of RHD-positive cases (borderline & definite RHD) versus RHD-negative cases. However, RHD-positive cases had a 4.5 times greater chance of having a sibling with definite RHD (p = 0.05) and this risk increased to 5.6 times greater chance if you limited the comparison to RHD-positive cases with definite RHD (n = 30, p = 0.03.”

The paper, “Targeted Echocardiographic Screening for Latent Rheumatic Heart Disease in Northern Uganda,” was published recently by PLoS and is among a dozen papers published this year about the group’s work in Africa, done under the aegis of the Children’s Research Institute global health initiative.

The World Health Organization previously has prioritized screening household contacts when an index case of tuberculosis (TB) is identified, the authors note. Like TB, RHD has a strong environmental component in that family members are exposed to the same poverty, overcrowding, and circulating streptococcal strains. In a country where the median age is 15.5, it is not practical to screen youths without a detailed plan, Dr. Beaton says. Additional work would need to be done to determine which tasks to shift to nurses, who are more plentiful, and how to best leverage portable, hand-held screening machines.

“Optimal implementation strategies, the who, when, in what setting, and how often to screen, have received little study to date, yet these details are critical to developing cost-effective and sustainable screening programs,” Aliku and co-authors write. “Our study suggests that siblings of children identified with latent RHD are a high-risk group, and should be prioritized for screening.”

Related resources:  Research at a Glance