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coronavirus

Single institution study finds high rates of cardiac complications in MIS-C

coronavirus

At this year’s AHA Scientific Sessions, cardiologists from Children’s National Hospital presented a poster about an interesting finding in children with MIS-C.

During the height of the pandemic, researchers at Children’s National Hospital discovered that as many as one half of children diagnosed with multisystem inflammatory disease in children (MIS-C) at the hospital developed cardiac complications including coronary artery abnormalities, even when diagnosed and treated promptly.

The data was shared as part of a poster presentation at the American Heart Association Scientific Sessions in November 2020. Though analysis was limited to the data from one institution’s confirmed MIS-C cases, the findings are significant enough to warrant further study.

Interestingly, the authors noted that the high rate of cardiac complications far exceeds the rate of similar issues in children with Kawasaki disease — another pediatric inflammatory syndrome that shares many common symptoms with MIS-C. The two are so similar that immunomodulation therapies successfully deployed in children with MIS-C were based on those developed to treat Kawasaki disease.

Knowledge of common cardiac complications in Kawasaki disease also flagged the need for routine echocardiograms in patients with MIS-C, which helped identify the higher rates of cardiac complications seen in the MIS-C patient population.

“This finding, however, is another data point that shows how MIS-C and Kawasaki disease have some specific differences needing further study,” says Ashraf Harahsheh, M.D., a pediatric cardiologist at Children’s National Hospital who studies Kawasaki disease and the first author on the new study.

“Previous clinical advancements made in Kawasaki disease set the stage for our response to MIS-C early on,” he said. ”Now we also need to understand MIS-C as its own syndrome so we can better address what we are seeing in this patient population,” he says.

While most of the cardiac findings resolved during follow up, long-term studies are needed to determine if the cardiac abnormalities are associated with major cardiac events later.

“This work will help inform the community of the importance of diagnosing children with MIS-C promptly and following clinical guidelines for necessary tests and treatments once MIS-C is diagnosed,” Harahsheh concludes.

Next, the research team plans to take a deep dive into patient demographics as well as findings from clinical, laboratory and electrocardiogram data for children who developed cardiac complications with MIS-C. The goal will be to refine treatment algorithms and potentially identify a subgroup of patients who may require different or more intense therapy to prevent cardiac complications.

American Heart Association Scientific Sessions 2020 Poster Session
Cardiac Complications of SARS CoV-2 Associated Multi-System Inflammatory Syndrome in Children (MIS-C)
P1306
9:00am – 10:00am
Fri, Nov 13 (CST)

Gram-positive-bacteria-Streptococcus-pyogenes

Assessing the risk factors in rheumatic heart disease

Gram-positive-bacteria-Streptococcus-pyogenes

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.”

Targeted echocardiographic screening for latent RHD in Northern Uganda

What’s Known
Echocardiograms use the echoes of sound waves to create “movies” of the beating heart, its valves, and other structures. While rheumatic heart disease (RHD) was prevalent in the United States as late as the 1900s, improved housing conditions and the availability of powerful medicines like antibiotics and penicillin have lowered its incidence to 0.04 to 0.06 cases per 1,000 U.S. children. In regions where streptococcal infections flourish, RHD remains a scourge. Using echocardiographic screening to identify latent RHD— which is apparent on echocardiography before the child has symptoms that can be spotted by clinicians—has the potential to reduce the disease’s global burden.

What’s New
Optimal implementation must account for whom to target, when, in which settings, and how often to screen. The team led by Children’s National Health System researchers and clinicians conducted the first family screening study in Northern Uganda to assess the utility of echocardiographic screening of first-degree relatives of children with latent RHD. They used existing school-based screening data to identify potential participants and invited all first-degree relatives older than 5 years for echocardiography screening. The study recruited 60 RHD-positive schoolchildren and matched them with 67 RHD-negative kids of similar age and gender. Some 1,122 family members were then screened. Children with any RHD were 4.5 times as likely to have a sibling with definite RHD, a risk that increased to 5.6 times if researchers looked solely at index cases with definite RHD. The team, led by Andrea Beaton, MD, a cardiologist at Children’s National, also found that mothers had a 9.3 percent rate of latent RHD—a high rate that was independent of whether their child was RHD-positive.

Questions for Future Research
Q: Many children living in RHD-endemic areas, exposed to the same environmental conditions as RHD-positive kids, are able to fend off disease. Are protective genes to credit for their resilience?
Q: What are the best approaches to train nurses and community workers in how to use lower-cost, handheld echocardiograms to facilitate large-scale screening in countries where healthcare resources are constrained?

Source:  Targeted Echocardiographic Screening for Latent Rheumatic Heart Disease in Northern Uganda: Evaluating Familial Risk Following Identification of an Index Case.” T. Aliku, C. Sable, A. Scheel, A. Tompsett, P. Lwabi, E. Okello, R. McCarter, M. Summar, and A. Beaton. Published online by PLoS June 13, 2016.