Rheumatic heart disease on an Eastern Arizona Reservation, 2007-2022.

Contemporary studies of rheumatic heart disease (RHD) within American Indian communities are lacking, despite recent work indicating high rates of group A streptococcus, the precursor to RHD. Utilizing retrospective chart review of the Indian Health Service, we sought to characterize the burden of acute rheumatic fever and RHD within an American Indian tribe in Eastern Arizona. Our study found that, in line with other high-income countries, RHD in the US continues to disproportionately impact native peoples, with rates 10 times that of the general population.

Acute rheumatic fever and rheumatic heart disease: updates in diagnosis and treatment.

PURPOSE OF REVIEW: To summarize the latest developments in rheumatic fever and rheumatic heart disease (RHD) prevention, (early) diagnosis, and treatment. RECENT FINDINGS: The revised Jones criteria have demonstrated increased sensitivity and specificity for rheumatic fever diagnosis in high-risk populations. The management of rheumatic fever remains symptom-based, with no treatment options proven to alter the disease course or prevent chronic RHD. The revised World Heart Federation (WHF) guidelines for the echocardiographic diagnosis of RHD encourage task-shifting of RHD screening, extending reach in endemic regions. These guidelines also present an A-D classification of RHD and provide recommendations for the management of early disease. Integrated models for RHD screening within existing health structures are emerging and automated intelligence is showing potential to support RHD screening and diagnosis. Innovative strategies to foster adherence and equitable access to secondary prophylaxis, such as re-examination of the efficacy of oral penicillin, trials of longer acting penicillin formulations and implants are underway. There is renewed interest and investment in a well tolerated and effective GAS vaccine. SUMMARY: We are living in a time of possibility with global acceleration to address the prevailing burden of RHD. Together, we can ensure that RHD does not once again fall off the global health agenda, until equitable elimination has been achieved.

Preintervention Wait Time and Survival in People With Rheumatic Heart Disease in Uganda.

BACKGROUND: There is an unmet surgical burden among people living with rheumatic heart disease (RHD) in Uganda. Nevertheless, risk factors associated with time to first intervention and preoperative mortality are poorly understood. METHODS: Individuals with RHD who met indications for valve surgery were identified using the Uganda National RHD Registry (January 2010-August 2022). Kaplan-Meier estimates and multivariable Cox proportional hazard models were used. RESULTS: Of the cohort with clinical RHD, 64% (1452 of 2269) met criteria for an index operation. Of those, 13.5% obtained a surgical intervention, whereas 30.6% died before the operation. The estimated likelihood of first operation was 50% at 9.3 years of follow-up (95% CI, 8.1-upper limit not reached). Intervention was more likely in men vs women (hazard ratio [HR], 1.78; 95% CI, 1.21-2.64), those with postsecondary education vs primary school or less (HR, 3.60; 95% CI, 1.88-6.89), and those with a history of atrial fibrillation (HR, 2.78; 95% CI, 1.63-4.76). Surgical intervention was less likely for adults vs those aged <18 years (HR, 0.49; 95% CI, 0.32-0.77) and those with New York Heart Association Functional Class III/IV vs I/II (HR, 0.51; 95% CI, 0.32-0.83). The median preoperative survival time among those awaiting first operation was 4.6 years (95% CI, 3.9-5.7 years). History of infective endocarditis, right ventricular dysfunction, pericardial effusion, atrial fibrillation, and having surgical indications for multiple valves were associated with increased probability of death. CONCLUSIONS: Our analysis revealed a prolonged time to first surgical intervention and high preintervention death for RHD in Uganda, with factors such as age, sex, and education level remaining barriers to obtaining surgery.

The Echocardiographic Diagnosis of Rheumatic Heart Disease: A Review of the Performance of the World Heart Federation Criteria 2012-2023.

Background: The World Heart Federation (WHF) published the first evidence-based guidelines on the echocardiographic diagnosis of rheumatic heart disease (RHD) in 2012. These guidelines have since been applied internationally in research and clinical practice. Substantial research has assessed the utility of the 2012 WHF criteria, including its applicability in low-resource settings. This article summarises the evidence regarding the performance of the guidelines. Methods: A scoping review assessing the performance of the guidelines was performed. Cochrane, Embase, Medline, PubMed Lilacs, Sielo, and Portal BVS databases were searched for studies on the performance of the guidelines between January 2012-March 2023, and 4047 manuscripts met the search criteria, of which 34 were included. This included papers assessing the specificity, inter-rater reliability, application using hand-carried ultrasound, and modification of the criteria for simplicity. The review followed the PRISMA Extension for Scoping Reviews guideline. Results: The WHF 2012 criteria were 100% specific for definite RHD when applied in low-prevalence populations. The criteria demonstrated substantial and moderate inter-rater reliability for detecting definite and borderline RHD, respectively. The inter-rater reliability for morphological features was lower than for valvular regurgitation. When applied to hand-carried ultrasound performed by an expert, modified versions of the criteria demonstrated a sensitivity and specificity range of 79-90% and 87-93% respectively for detecting any RHD, performing best for definite RHD. The sensitivity and the specificity were reduced when performed in task-sharing but remains moderately accurate. Conclusion: The WHF 2012 criteria provide clear guidance for the echocardiographic diagnosis of RHD that is reproducible and applicable to a range of echocardiographic technology. Furthermore, the criteria are highly specific and particularly accurate for detecting definite RHD. There are limitations in applying all aspects of the criteria in specific settings, including task-sharing. This summary of evidence can inform the updated version of the WHF guidelines to ensure improved applicability in all RHD endemic regions.

Intramuscular versus enteral penicillin prophylaxis to prevent progression of rheumatic heart disease: Study protocol for a noninferiority randomized trial (the GOALIE trial).

BACKGROUND: Rheumatic Heart Disease (RHD) persists as a major cardiovascular driver of mortality and morbidity among young people in low-and middle-income countries. Secondary antibiotic prophylaxis (SAP) with penicillin remains the cornerstone of RHD control, however, suboptimal treatment adherence undermines most secondary prevention programs. Many of the barriers to optimal SAP adherence are specific to the intramuscular form of penicillin and may potentially be overcome by use of oral penicillin. This noninferiority trial is comparing the efficacy of intramuscular to oral penicillin SAP to prevent progression of mild RHD at 2 years. METHODS/DESIGN: The Intramuscular vs Enteral Penicillin Prophylaxis to Prevent Progression of Rheumatic Heart Disease (GOALIE) trial is randomizing Ugandan children aged 5 to 17 years identified by echocardiographic screening with mild RHD (Stage A or B as defined by 2023 World Heart Federation criteria) to Benzathine Benzyl Penicillin G (BPG arm, every-28-day intramuscular penicillin) or Phenoxymethyl Penicillin (Pen V arm, twice daily oral penicillin) for a period of 2 years. A blinded echocardiography adjudication panel of 3 RHD experts and 2 cardiologists is determining the echocardiographic stage of RHD at enrollment and will do the same at study completion by consensus review. Treatment adherence and study retention are supported through peer support groups and case management strategies. The primary outcome is the proportion of children in the Pen V arm who progress to more advanced RHD compared to those in the BPG arm. Secondary outcomes are patient-reported outcomes (treatment acceptance, satisfaction, and health related quality of life), costs, and cost-effectiveness of oral compared to intramuscular penicillin prophylaxis for RHD. A total sample size of 1,004 participants will provide 90% power to demonstrate noninferiority using a margin of 4% with allowance for 7% loss to follow-up. Participant enrollment commenced in October 2023 and final participant follow-up is expected in December 2026. The graphical abstract (Fig. 1) summarizes the flow of echocardiographic screening, participant enrollment and follow-up. DISCUSSION: The GOALIE trial is critical in global efforts to refine a pragmatic approach to secondary prevention for RHD control. GOALIE insists that the inferiority of oral penicillin be proven contemporarily and against the most important near-term clinical outcome of progression of RHD severity. This work also considers other factors that could influence the adoption of oral prophylaxis and change the calculus for acceptable efficacy including patient-reported outcomes and costs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05693545.

Silent Acute Rheumatic Fever Unmasked by Using Handheld Echocardiography for Febrile Children Presenting in a Rheumatic Heart Disease-Endemic Area.

OBJECTIVE: To understand the burden of acute rheumatic fever (ARF) among children living in low-income countries who present to the hospital with febrile illness and to determine the role of handheld echocardiography (HHE) in uncovering subclinical carditis as a major manifestation of ARF. STUDY DESIGN: This was a cross-sectional study carried at the Pediatric Hospital in Al Obeid, North Kordofan, Sudan, from September 2022 to January 2023 and including febrile children 3 through 18 years of age with or without clinical features of ARF and without another cause for their fever (not excluding malaria). History, examination, blood investigations, and HHE were done. ARF was diagnosed according to the Jones criteria. Clinical ARF was diagnosed if there was a major clinical Jones criterion and silent ARF if the only major Jones criteria was subclinical carditis. RESULTS: The study cohort included 400 children with a mean age of 9 years. Clinical ARF was diagnosed in 95 patients (95/400, 24%), most of whom presented with a joint major manifestation (88/95, 93%). Among the 281 children who did not present with a clinical manifestation of ARF, HHE revealed rheumatic heart disease (RHD) in 44 patients (44/281, 16%); 31 of them fulfilled criteria for silent ARF (31/281, 11%). HHE increased the detection of ARF by 24%. HHE revealed mild RHD in 41 of 66 (62%) and moderate or severe RHD in 25 of 66 (38%) patients. Both sensitivity and specificity of HHE compared with standard echocardiography were 88%. CONCLUSIONS: There is a significant burden of ARF among febrile children in Sudan. HHE increased the sensitivity of diagnosis, with 11% of children having subclinical carditis as their only major manifestation (ie, silent ARF). RHD-prevention policies need to prioritize decentralization of echocardiography to improve ARF detection.

Outcomes of rheumatic fever in Uganda: a prospective cohort study.

BACKGROUND: Rheumatic heart disease is the largest contributor to cardiac-related mortality in children worldwide. Outcomes in endemic settings after its antecedent illness, acute rheumatic fever, are not well understood. We aimed to describe 3-5 year mortality, acute rheumatic fever recurrence, changes in carditis, and correlates of mortality after acute rheumatic fever. METHODS: We conducted a prospective cohort study of Ugandan patients aged 4-23 years who were diagnosed with definite acute rheumatic fever using the modified 2015 Jones criteria from July 1, 2017, to March 31, 2020, enrolled at three rheumatic heart disease registry sites in Uganda (in Mbarara, Mulago, or Lira), and followed up for at least 1 year after diagnosis. Patients with congenital heart disease were excluded. Patients underwent annual review, most recently in August, 2022. We calculated rates of mortality and acute rheumatic fever recurrence, tabulated changes in carditis, performed Kaplan-Meier survival analyses, and used Cox regression models to identify correlates of mortality. FINDINGS: Data were collected between Sept 1 and Sept 30, 2022. Of 182 patients diagnosed with definite acute rheumatic fever, 156 patients were included in the analysis. Of these 156 patients (77 [49%] male and 79 (51%) female; data on ethnicity not collected), 25 (16%) died, 21 (13%) had a cardiac-related death, and 17 (11%) had recurrent acute rheumatic fever over a median of 4·3 (IQR 3·0-4·8) years. 16 (24%) of the 25 deaths occurred within 1 year. Among 131 (84%) of 156 survivors, one had carditis progression by echo. Moderate-to-severe carditis (hazard ratio 12·7 [95% CI 3·9-40·9]) and prolonged PR interval (hazard ratio 4·4 [95% CI 1·7-11·2]) at acute rheumatic fever diagnosis were associated with increased cardiac-related mortality. INTERPRETATION: These are the first contemporary data from sub-Saharan Africa on medium-term acute rheumatic fever outcomes. Mortality rates exceeded those reported elsewhere. Most decedents already had chronic carditis at initial acute rheumatic fever diagnosis, suggesting previous undiagnosed episodes that had already compounded into rheumatic heart disease. Our data highlight the large burden of undetected acute rheumatic fever in these settings and the need for improved awareness of and diagnostics for acute rheumatic fever to allow earlier detection. FUNDING: Strauss Award at Cincinnati Children's Hospital, American Heart Association, and Wellcome Trust.

Using Artificial Intelligence for Rheumatic Heart Disease Detection by Echocardiography: Focus on Mitral Regurgitation.

BACKGROUND: Identification of children with latent rheumatic heart disease (RHD) by echocardiography, before onset of symptoms, provides an opportunity to initiate secondary prophylaxis and prevent disease progression. There have been limited artificial intelligence studies published assessing the potential of machine learning to detect and analyze mitral regurgitation or to detect the presence of RHD on standard portable echocardiograms. METHODS AND RESULTS: We used 511 echocardiograms in children, focusing on color Doppler images of the mitral valve. Echocardiograms were independently reviewed by an expert adjudication panel. Among 511 cases, 229 were normal, and 282 had RHD. Our automated method included harmonization of echocardiograms to localize the left atrium during systole using convolutional neural networks and RHD detection using mitral regurgitation jet analysis and deep learning models with an attention mechanism. We identified the correct view with an average accuracy of 0.99 and the correct systolic frame with an average accuracy of 0.94 (apical) and 0.93 (parasternal long axis). It localized the left atrium with an average Dice coefficient of 0.88 (apical) and 0.9 (parasternal long axis). Maximum mitral regurgitation jet measurements were similar to expert manual measurements (P value=0.83) and a 9-feature mitral regurgitation analysis showed an area under the receiver operating characteristics curve of 0.93, precision of 0.83, recall of 0.92, and F1 score of 0.87. Our deep learning model showed an area under the receiver operating characteristics curve of 0.84, precision of 0.78, recall of 0.98, and F1 score of 0.87. CONCLUSIONS: Artificial intelligence has the potential to detect RHD as accurately as expert cardiologists and to improve with more data. These innovative approaches hold promise to scale echocardiography screening for RHD.

User-Centered Design to Develop Automated Short Message Service Messaging for Patient Support of Rheumatic Heart Disease Secondary Antibiotic Prophylaxis.

BACKGROUND: The Active Community Case Management Platform is a cloud-based technology developed to facilitate rheumatic heart disease case management by health care providers. This study aimed to design and pilot an automated short message service (SMS) intervention to support secondary prophylaxis adherence. METHODS AND RESULTS: We developed a concise library of messages to support secondary antibiotic prophylaxis. The SMS intervention used TextIT, an interface that enables users to send out interactive SMS messages at scale. The message bank was piloted in a cohort of 50 patients with rheumatic heart disease randomized into 2 groups. Group 1 received standard support (nurse-led/Active Community Case Management Platform). Group 2 received standard support plus SMS intervention for 2 months in the Lira and Gulu districts of Northern Uganda. We collected qualitative data on participants' experiences and assessed treatment adherence. Using a sequential user-centered process consisting of 4 phases (phases 1-4), we developed a message bank (n=43) deployed during our pilot study. There were no between-group differences in treatment adherence or acceptance. Interviews of participants indicated that the intervention was viewed positively. A total of 75% of SMS recipients responded to the messages, and 25% called the study staff to acknowledge receipt of text messages. CONCLUSIONS: This study has successfully developed a bank of SMS messages to support secondary antibiotic prophylaxis adherence. We have demonstrated the feasibility and acceptability of SMS technology in rheumatic heart disease care management. Future work will include integrating automated SMS into the Active Community Case Management Platform and a larger study of integrated SMS to reduce health care worker burden for patient support and improve adherence to secondary antibiotic prophylaxis.

2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Advancing Cardiovascular Health Equity Globally Through Digital Technologies.

Cardiovascular diseases (CVDs) remain the leading cause of death and disability worldwide. Digital health technologies are important public health interventions for addressing the burden of cardiovascular disease. In this article, we discuss the importance of translating digital innovations in research-funded projects to low-resource settings globally to advance global cardiovascular health equity. We also discuss current global cardiovascular health inequities and the digital health divide within and between countries. We present various considerations for translating digital innovations across different settings across the globe, including reciprocal innovation, a "bidirectional, co-constituted, and iterative exchange of ideas, resources, and innovations to address shared health challenges across diverse global settings." In this case, afferent reciprocal innovations may flow from high-income countries toward low- and middle-income countries, and efferent reciprocal innovations may be exported to high-income countries from low- and middle-income countries with adaptation. Finally, we discuss opportunities for bidirectional learning between local and global institutions and highlight examples of projects funded through the American Heart Association Health and Innovation Strategically Funded Research Network that have been adapted to lower-resource settings or have the potential to be adapted to lower-resource settings.

Deployment of Point-of-Care Echocardiography to Improve Cardiac Diagnostic Access Among American Indians.

BACKGROUND: American Indians face significant barriers to diagnosis and management of cardiovascular disease. We sought to develop a real-world implementation model for improving access to echocardiography within the Indian Health Service, the American Indian Structural Heart Disease Partnership. METHODS AND RESULTS: The American Indian Structural Heart Disease Partnership was implemented and evaluated via a 4-step process of characterizing the system where it would be instituted, building point-of-care echocardiography capacity, deploying active case finding for structural heart disease, and evaluating the approach from the perspective of the clinician and patient. Data were collected and analyzed using a parallel convergent mixed methods approach. Twelve health care providers successfully completed training in point-of-care echocardiography. While there was perceived usefulness of echocardiography, providers found it difficult to integrate screening point-of-care echocardiography into their workday given competing demands. By the end of 12 months, 6 providers continued to actively utilize point-of-care echocardiography. Patients who participated in the study felt it was an acceptable and effective approach. They also identified access to transportation as a notable challenge to accessing echocardiograms. Over the 12-month period, a total of 639 patients were screened, of which 36 (5.6%) had a new clinically significant abnormal finding. CONCLUSIONS: The American Indian Structural Heart Disease Partnership model exhibited several promising strategies to improve access to screening echocardiography for American Indian populations. However, competing priorities for Indian Health Service providers' time limited the amount of integration of screening echocardiography into outpatient practice. Future endeavors should explore community-based solutions to develop a more sustainable model with greater impact on case detection, disease management, and improved outcomes.

2023 World Heart Federation guidelines for the echocardiographic diagnosis of rheumatic heart disease.

Rheumatic heart disease (RHD) is an important and preventable cause of morbidity and mortality among children and young adults in low-income and middle-income countries, as well as among certain at-risk populations living in high-income countries. The 2012 World Heart Federation echocardiographic criteria provided a standardized approach for the identification of RHD and facilitated an improvement in early case detection. The 2012 criteria were used to define disease burden in numerous epidemiological studies, but researchers and clinicians have since highlighted limitations that have prompted a revision. In this updated version of the guidelines, we incorporate evidence from a scoping review, an expert panel and end-user feedback and present an approach for active case finding for RHD, including the use of screening and confirmatory criteria. These guidelines also introduce a new stage-based classification for RHD to identify the risk of disease progression. They describe the latest evidence and recommendations on population-based echocardiographic active case finding and risk stratification. Secondary antibiotic prophylaxis, echocardiography equipment and task sharing for RHD active case finding are also discussed. These World Heart Federation 2023 guidelines provide a concise and updated resource for clinical and research applications in RHD-endemic regions.