Prevalence of Cardiac Dysfunction in Malawian Children With Severe Febrile Illness.

OBJECTIVES: To investigate the prevalence of left ventricular systolic dysfunction (LVSD) in Malawian children with severe febrile illness and to explore associations between LVSD and mortality and lactate levels. DESIGN: Prospective observational study. SETTING: Pediatric ward of a tertiary government referral hospital in Malawi. PATIENTS: Children between 60 days and 10 years old with severe febrile illness (fever with at least one sign of impaired perfusion plus altered mentation or respiratory distress) were enrolled at admission from October 2017 to February 2018. INTERVENTIONS: Focused cardiac ultrasound (FoCUS) was performed, and serum lactate was measured for each child at enrollment, with repeat FoCUS the following day. LV systolic function was later categorized as normal, reduced, severely reduced, or hyperdynamic by two pediatric cardiologists blinded to clinical course and outcomes. MEASUREMENTS AND MAIN RESULTS: Fifty-four children were enrolled. LVSD was present in 14 children (25.9%; 95% CI, 15.4-40.3%), of whom three had severely reduced function. Thirty patients (60%) had a lactate greater than 2.5 mmol/L, of which 20 (40%) were markedly elevated (>5 mmol/L). Ten children died during admission (18.5%). Of children who survived, 22.7% had decreased LV systolic function versus 40% of those who died. Dysfunction was not associated with mortality or elevated lactate. CONCLUSIONS: Cardiac dysfunction may be present in one in four Malawian children with severe febrile illness, and mortality in these patients is especially high. Larger studies are needed to further clarify the role cardiac dysfunction plays in mortality and integrate practical bedside assessments for decision support around individualized resuscitation strategies.

Acute Rheumatic Fever.

The incidence of acute rheumatic fever (ARF) is 8 to 51 per 100,000 people worldwide. It most commonly affects children 5 to 15 years of age after a group A streptococcal infection. Overcrowding and poor socioeconomic conditions are directly proportional to the incidence of ARF. Rheumatic carditis is a manifestation of ARF that may lead to rheumatic heart disease (RHD). Timely treatment of group A streptococcal infection can prevent ARF, and penicillin prophylaxis can prevent recurrence of ARF. Prevention of recurrent ARF is the most effective way to prevent RHD. ARF is diagnosed using the 2015 modified Jones criteria. There is no gold standard laboratory test. Therefore, clinicians need to be aware of the clinical signs and symptoms of ARF to include in their differential diagnosis when seeing such patients. Secondary prophylaxis with benzathine penicillin G has been shown to decrease the incidence of RHD and is key to RHD control. Clinicians need to understand the implications of secondary prophylaxis for ARF. There is also a need to improve ARF diagnosis, to find novel therapies to reduce the incidence of ARF, and to reduce the prevalence of RHD. RHD research is neglected and underfunded. Thus, there is also a need for RHD advocacy and public health awareness to increase research on RHD.

Circumflex aorta with double aortic arch in an infant.

Circumflex aorta and double aortic arch are two forms of rare vascular rings. We present a case of an infant who was diagnosed with circumflex aorta and double aortic arch, and describe the surgical management of this rare anomaly.

Task shifting to clinical officer-led echocardiography screening for detecting rheumatic heart disease in Malawi, Africa.

BACKGROUND: Echocardiographic screening for rheumatic heart disease in asymptomatic children may result in early diagnosis and prevent progression. Physician-led screening is not feasible in Malawi. Task shifting to mid-level providers such as clinical officers may enable more widespread screening. Hypothesis With short-course training, clinical officers can accurately screen for rheumatic heart disease using focussed echocardiography. METHODS: A total of eight clinical officers completed three half-days of didactics and 2 days of hands-on echocardiography training. Clinical officers were evaluated by performing screening echocardiograms on 20 children with known rheumatic heart disease status. They indicated whether children should be referred for follow-up. Referral was indicated if mitral regurgitation measured more than 1.5 cm or there was any measurable aortic regurgitation. The κ statistic was calculated to measure referral agreement with a paediatric cardiologist. Sensitivity and specificity were estimated using a generalised linear mixed model, and were calculated on the basis of World Heart Federation diagnostic criteria. RESULTS: The mean κ statistic comparing clinical officer referrals with the paediatric cardiologist was 0.72 (95% confidence interval: 0.62, 0.82). The κ value ranged from a minimum of 0.57 to a maximum of 0.90. For rheumatic heart disease diagnosis, sensitivity was 0.91 (95% confidence interval: 0.86, 0.95) and specificity was 0.65 (95% confidence interval: 0.57, 0.72). CONCLUSION: There was substantial agreement between clinical officers and paediatric cardiologists on whether to refer. Clinical officers had a high sensitivity in detecting rheumatic heart disease. With short-course training, clinical officer-led echo screening for rheumatic heart disease is a viable alternative to physician-led screening in resource-limited settings.

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.

Decentralization and Integration of Advanced Cardiac Care for the World's Poorest Billion Through the PEN-Plus Strategy for Severe Chronic Non-Communicable Disease.

Rheumatic and congenital heart disease, cardiomyopathies, and hypertensive heart disease are major causes of suffering and death in low- and lower middle-income countries (LLMICs), where the world's poorest billion people reside. Advanced cardiac care in these counties is still predominantly provided by specialists at urban tertiary centers, and is largely inaccessible to the rural poor. This situation is due to critical shortages in diagnostics, medications, and trained healthcare workers. The Package of Essential NCD Interventions - Plus (PEN-Plus) is an integrated care model for severe chronic noncommunicable diseases (NCDs) that aims to decentralize services and increase access. PEN-Plus strategies are being initiated by a growing number of LLMICs. We describe how PEN-Plus addresses the need for advanced cardiac care and discuss how a global group of cardiac organizations are working through the PEN-Plus Cardiac expert group to promote a shared operational strategy for management of severe cardiac disease in high-poverty settings.

Correction: Decentralization and Integration of Advanced Cardiac Care for the World's Poorest Billion Through the PEN-Plus Strategy for Severe Chronic Non-Communicable Disease.

[This corrects the article DOI: 10.5334/gh.1313.].

Machine Learning for Pediatric Echocardiographic Mitral Regurgitation Detection.

BACKGROUND: Echocardiography-based screening for valvular disease in at-risk asymptomatic children can result in early diagnosis. These screening programs, however, are resource intensive and may not be feasible in many resource-limited settings. Automated echocardiographic diagnosis may enable more widespread echocardiographic screening, early diagnosis, and improved outcomes. In this feasibility study, the authors sought to build a machine learning model capable of identifying mitral regurgitation (MR) on echocardiography. METHODS: Echocardiograms were labeled by clip for view and by frame for the presence of MR. The labeled data were used to build two convolutional neural networks to perform the stepwise tasks of classifying the clips (1) by view and (2) by the presence of any MR, including physiologic, in parasternal long-axis color Doppler views. The view classification model was developed using 66,330 frames, and model performance was evaluated using a hold-out testing data set with 45 echocardiograms (11,730 frames). The MR detection model was developed using 938 frames, and model performance was evaluated using a hold-out testing data set with 42 echocardiograms (182 frames). Metrics to evaluate model performance included accuracy, precision, recall, F1 score (average of precision and recall, ranging from 0 to 1, with 1 suggesting perfect precision and recall), and receiver operating characteristic analysis. RESULTS: For the parasternal long-axis view with color Doppler, the view classification convolutional neural network achieved an F1 score of 0.97. The MR detection convolutional neural network achieved testing accuracy of 0.86 and an area under the receiver operating characteristic curve of 0.91. CONCLUSIONS: A machine learning model is capable of discerning MR on transthoracic echocardiography. This is an encouraging step toward machine learning-based diagnosis of valvular heart disease on pediatric echocardiography.

The Use of Artificial Intelligence Guidance for Rheumatic Heart Disease Screening by Novices.

INTRODUCTION: A novel technology utilizing artificial intelligence (AI) to provide real-time image-acquisition guidance, enabling novices to obtain diagnostic echocardiographic images, holds promise to expand the reach of echo screening for rheumatic heart disease (RHD). We evaluated the ability of nonexperts to obtain diagnostic-quality images in patients with RHD using AI guidance with color Doppler. METHODS: Novice providers without prior ultrasound experience underwent a 1-day training curriculum to complete a 7-view screening protocol using AI guidance in Kampala, Uganda. All trainees then scanned 8 to 10 volunteer patients using AI guidance, half RHD and half normal. The same patients were scanned by 2 expert sonographers without the use of AI guidance. Images were evaluated by expert blinded cardiologists to assess (1) diagnostic quality to determine presence/absence of RHD and (2) valvular function and (3) to assign an American College of Emergency Physicians score of 1 to 5 for each view. RESULTS: Thirty-six novice participants scanned a total of 50 patients, resulting in a total of 462 echocardiogram studies, 362 obtained by nonexperts using AI guidance and 100 obtained by expert sonographers without AI guidance. Novice images enabled diagnostic interpretation in >90% of studies for presence/absence of RHD, abnormal MV morphology, and mitral regurgitation (vs 99% by experts, P ≤ .001). Images were less diagnostic for aortic valve disease (79% for aortic regurgitation, 50% for aortic stenosis, vs 99% and 91% by experts, P < .001). The American College of Emergency Physicians scores of nonexpert images were highest in the parasternal long-axis images (mean, 3.45; 81% ≥ 3) compared with lower scores for apical 4-chamber (mean, 3.20; 74% ≥ 3) and apical 5-chamber images (mean, 2.43; 38% ≥ 3). CONCLUSIONS: Artificial intelligence guidance with color Doppler is feasible to enable RHD screening by nonexperts, performing significantly better for assessment of the mitral than aortic valve. Further refinement is needed to optimize acquisition of color Doppler apical views.

Research opportunities for the primary prevention and management of acute rheumatic fever and rheumatic heart disease: a National Heart, Lung, and Blood Institute workshop report.

Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) encompasses the timely diagnosis and adequate treatment of the superficial group A Streptococcus (GAS) infections pharyngitis and impetigo. GAS is the only known inciting agent in the pathophysiology of the disease. However, sufficient evidence indicates that the uptake and delivery of primary prevention approaches in RHD-endemic regions are significantly suboptimal. This report presents expert deliberations on priority research and implementation opportunities for primary prevention of ARF/RHD that were developed as part of a workshop convened by the US National Heart, Lung, and Blood Institute in November 2021. The opportunities identified by the Primary Prevention Working Group encompass epidemiological, laboratory, clinical, implementation and dissemination research domains and are anchored on five pillars including: (A) to gain a better understanding of superficial GAS infection epidemiology to guide programmes and policies; (B) to improve diagnosis of superficial GAS infections in RHD endemic settings; (C) to develop scalable and sustainable models for delivery of primary prevention; (D) to understand potential downstream effects of the scale-up of primary prevention and (E) to develop and conduct economic evaluations of primary prevention strategies in RHD endemic settings. In view of the multisectoral stakeholders in primary prevention strategies, we emphasise the need for community co-design and government engagement, especially in the implementation and dissemination research arena. We present these opportunities as a reference point for research organisations and sponsors who aim to contribute to the increasing momentum towards the global control and prevention of RHD.

Development and User Testing of a Dynamic Tool for Rheumatic Heart Disease Management.

OBJECTIVE: Most rheumatic heart disease (RHD) registries are static and centralized, collecting epidemiological and clinical data without providing tools to improve care. We developed a dynamic cloud-based RHD case management application with the goal of improving care for patients with RHD in Uganda. METHODS: The Active Community Case Management Tool (ACT) was designed to improve community-based case management for chronic disease, with RHD as the first test case. Global and local partner consultation informed selection of critical data fields and prioritization of application functionality. Multiple stages of review and revision culminated in user testing of the application at the Uganda Heart Institute. RESULTS: Global and local partners provided feedback of the application via survey and interview. The application was well received, and top considerations included avenues to import existing patient data, considering a minimum data entry form, and performing a situation assessment to tailor ACT to the health system setup for each new country. Test users completed a postuse survey. Responses were favorable regarding ease of use, desire to use the application in regular practice, and ability of the application to improve RHD care in Uganda. Concerns included appropriate technical skills and supports and potential disruption of workflow. CONCLUSION: Creating the ACT application was a dynamic process, incorporating iterative feedback from local and global partners. Results of the user testing will help refine and optimize the application. The ACT application showed potential for utility and integration into existing care models in Uganda.

Penicillin Reactions in Patients With Severe Rheumatic Heart Disease: A Presidential Advisory From the American Heart Association.

Secondary antibiotic prophylaxis with regular intramuscular benzathine penicillin G (BPG) is the cornerstone of rheumatic heart disease management. However, there is a growing body of evidence that patients with rheumatic heart disease who have severe valvular heart disease with or without reduced ventricular function may be dying from cardiovascular compromise following BPG injections. This advisory responds to these concerns and is intended to: (1) raise awareness, (2) provide risk stratification, and (3) provide strategies for risk reduction. Based on available evidence and expert opinion, we have divided patients into low- and elevated-risk groups, based on symptoms and the severity of underlying heart disease. Patients with elevated risk include those with severe mitral stenosis, aortic stenosis, and aortic insuffiency; those with decreased left ventricular systolic dysfunction; and those with no symptoms. For these patients, we believe the risk of adverse reaction to BPG, specifically cardiovascular compromise, may outweigh its theoretical benefit. For patients with elevated risk, we newly advise that oral prophylaxis should be strongly considered. In addition, we advocate for a multifaceted strategy for vasovagal risk reduction in all patients with rheumatic heart disease receiving BPG. As current guidelines recommend, all low-risk patients without a history of penicillin allergy or anaphylaxis should continue to be prescribed BPG for secondary antibiotic prophylaxis. We publish this advisory in the hopes of saving lives and avoiding events that can have devastating effects on patient and clinician confidence in BPG.

Outcomes of Echocardiography-Detected Rheumatic Heart Disease: Validating a Simplified Score in Cohorts From Different Countries.

Background The natural history of latent rheumatic heart disease (RHD) detected by echocardiography remains unclear. We aimed to assess the accuracy of a simplified score based on the 2012 World Heart Federation criteria in predicting mid-term RHD echocardiography outcomes in children from 4 different countries. Methods and Results Patient-level baseline and follow-up data of children with latent RHD from 4 countries (Australia, n=62; Brazil, n=197; Malawi, n=40; New Zealand, n=94) were combined. A simplified echocardiographic scoring system previously developed from Brazilian and Ugandan cohorts, consisting of 5 point-based variables with respective weights, was applied: mitral valveanterior leaflet thickening (weight=3), excessive leaflettip motion (3), regurgitation jet length ≥2 cm (6), aortic valvefocal thickening (4), and any regurgitation (5). Unfavorable outcome was defined as worsening diagnostic category, persistent definite RHD or development/worsening of valve regurgitation/stenosis. The score model was updated using methods for recalibration. 393 patients (314 borderline, 79 definite RHD) with median follow-up of 36 (interquartile range, 25-48) months were included. Median age was 14 (interquartile range, 11-16) years and secondary prophylaxis was prescribed to 16%. The echocardiographic score model applied to this external population showed significant association with unfavorable outcome (hazard ratio, 1.10; 95% CI, 1.04-1.16; P=0.001). Unfavorable outcome rates in low (≤5 points), intermediate (6-9), and high-risk (≥10) children at 3-year follow-up were 14.3%, 20.8%, and 38.5% respectively (P<0.001). The updated score model showed good performance in predicting unfavorable outcome. Conclusions The echocardiographic score model for predicting RHD outcome was updated and validated for different latent RHD populations. It has potential utility in the clinical and screening setting for risk stratification of latent RHD.

Rheumatic Heart Disease in the United States: Forgotten But Not Gone: Results of a 10 Year Multicenter Review.

Background Recent evaluation of rheumatic heart disease (RHD) mortality demonstrates disproportionate disease burden within the United States. However, there are few contemporary data on US children living with acute rheumatic fever (ARF) and RHD. Methods and Results Twenty-two US pediatric institutions participated in a 10-year review (2008-2018) of electronic medical records and echocardiographic databases of children 4 to 17 years diagnosed with ARF/RHD to determine demographics, diagnosis, and management. Geocoding was used to determine a census tract-based socioeconomic deprivation index. Descriptive statistics of patient characteristics and regression analysis of RHD classification, disease severity, and initial antibiotic prescription according to community deprivation were obtained. Data for 947 cases showed median age at diagnosis of 9 years; 51% and 56% identified as male and non-White, respectively. Most (89%) had health insurance and were first diagnosed in the United States (82%). Only 13% reported travel to an endemic region before diagnosis. Although 96% of patients were prescribed secondary prophylaxis, only 58% were prescribed intramuscular benzathine penicillin G. Higher deprivation was associated with increasing disease severity (odds ratio, 1.25; 95% CI, 1.08-1.46). Conclusions The majority of recent US cases of ARF and RHD are endemic rather than the result of foreign exposure. Children who live in more deprived communities are at risk for more severe disease. This study demonstrates a need to improve guideline-based treatment for ARF/RHD with respect to secondary prophylaxis and to increase research efforts to better understand ARF and RHD in the United States.

Education: The prevention of acute rheumatic fever and rheumatic heart disease in Malawi.

Background: With an estimated prevalence of 183,200 cases, rheumatic heart disease (RHD) is a major public health problem in Malawi. However, patients in Malawi with advanced RHD are left with substantial and life-threatening disability because there are no surgical options available in our country at present. In order to tackle this epidemic, it is critical to provide appropriate education and attempt to diagnose the disease earlier. In this study, we aimed to pilot a RHD education program that could be subsequently adopted country-wide. Methods: We designed and piloted a RHD educational program targeting health providers at Kamuzu Central Hospital in Lilongwe, Malawi. This involved three half-day workshops. These workshops were facilitated by a paediatric cardiologist and a paediatric nurse. Tests were administered before and after the workshops; we also provided questionnaires and requested feedback evaluations. A total of sixty-five participants (51 nurses, 3 doctors, 9 clinical officers and 2 unspecified personnel) participated in our workshops. Results: Concerns were voiced and addressed relating to the safety of benzathine penicillin. Post-workshop questionnaires revealed that participants were much more comfortable prescribing or injecting benzathine penicillin after the workshop, as indicated by an improvement in the comfort level from 2.8 to 4.5 in nurses, and from 3.4 to 5 in clinicians (using a Likert scale of 1 to 5, p< 0.01). Pre-test knowledge scores improved from 43.8% to 78.5% (p< 0.01). Overall, the workshops received good feedback with an overall rating of 4.8 out of 5 (n=61, range 3-5). Conclusion: Our analysis showed that practical sessions relating to acute rheumatic fever and RHD in Malawi must address the safety and administration of penicillin. Our pilot workshops could serve as the educational backbone for a national RHD prevention program in Malawi.

Two-year evolution of latent rheumatic heart disease in Malawi.

BACKGROUND: In asymptomatic children, screening echocardiography has been used to attempt to diagnose rheumatic heart disease (RHD) at an early stage (latent RHD). World Heart Federation guidelines have standardized categorization of "definite," "borderline," or no RHD by echo findings. The progression of RHD diagnosed through echo screening is not known. In 2014, we screened 1450 schoolchildren in Malawi. OBJECTIVE: Our objective was to evaluate 2-year RHD evolution among those diagnosed through screening. METHODS: Two-year follow-up echocardiograms of those diagnosed with latent RHD were read by a primary, secondary, then third reader if there was disagreement. Progression or regression of both definite and borderline groups were tabulated. Penicillin adherence, age, gender, number in home, and household income were compared between those with definite RHD who regressed to borderline and those that stayed definite. We utilized the local system used to track HIV defaulters in order to bring participants back into care. Comparisons were made using Fisher's exact and Wilcoxon rank-sum tests. RESULTS: Of the 39 with borderline RHD, 1 was lost to follow-up (2.6%), 1 progressed to definite (2.6%), 19 remained borderline (48.7%), 17 (43.6%) regressed to normal, and 1 was reclassified as mitral valve prolapse (2.6%). Of the 11 with definite RHD, 6 (54.5%) remained definite, 4 regressed to borderline (36.4%), and 1 regressed to normal (9.1%). Two of 11 with definite RHD had penicillin adherence above 80% for the 2-year follow-up period. There were no differences in adherence, gender, age, household income, or number in household between those with definite RHD that regressed to borderline and those who did not (P > .19). CONCLUSIONS: Borderlines had a very low progression rate to definite RHD. A strength of our study was a high retention rate (98%). Longer follow-up is needed to determine expected disease evolution.

Decreased Prevalence of Rheumatic Heart Disease Confirmed Among HIV-positive Youth.

BACKGROUND: There is geographical overlap between areas endemic for rheumatic heart disease (RHD) and those endemic for HIV. A recent pilot study demonstrated that children living with HIV might be at less risk for RHD development; however, the sample size was too small to make definitive conclusions. Our objective was to determine the prevalence of RHD among HIV-positive children in Uganda. METHODS: We conducted a prospective, cross-sectional study of HIV-positive children (5-15 years of age) receiving care at the Baylor Uganda HIV Clinic, Kampala, Uganda. A focused echocardiogram and chart review was performed. A sample size of 988 children was needed to provide 80% power to detect a difference in population prevalence between HIV-positive children and the general population, 2.97% [95% confidence interval (CI): 2.70-3.24%], based on previous reports. RESULTS: Screening echocardiography of 993 HIV-positive children found 15 individuals (1.5%; 95% CI: 0.88%-2.54%) with RHD. Of these 15, 2 were classified as definite RHD and 13 as borderline RHD. The majority of children had isolated mitral valve disease (93%). Children found to have RHD were older than those without RHD, 12 versus 10 years of age (P = 0.004). When separated based on geographic location, the prevalence of RHD among HIV-positive children from Kampala was 1.28% (95% CI: 0.63%-2.51%) compared with 2.1% (95% CI: 0.89%-4.89%) in those from outside Kampala. CONCLUSIONS: Children living with HIV have a lower prevalence of RHD than the general pediatric population. Further studies are needed to explore this protective association.

Pattern of inpatient pediatric cardiology consultations in sub-Saharan Africa.

Malawi is one of the poorest nations in the world, ranked 151st among 195 countries by the World Bank, with an under-5-year mortality rate of 63 per 1000 live births. There are no previous studies describing the spectrum of inpatient pediatric cardiology consultations in sub-Saharan Africa. A descriptive cohort study was performed at Kamuzu Central Hospital (KCH), a tertiary care hospital in Lilongwe, Malawi. Demographic, anthropometric, and clinical information for all cardiology consults patients aged 0-18 years admitted to the children's wards over a period of 1 month was reviewed. Seventy-three consults and 69 echocardiograms were performed on 71 patients (35 males, 38 females). The median (IQR) age was 3.1 years (9 months-10.5 years). About 53% (39/73) had failure to thrive, 4.1% (3/73) were sero-reactive for HIV and 100% (73/73) were fully immunized for age per the Expanded Program on Immunization schedule. Seventy-four percent of the echocardiograms were abnormal, with 34.8% (24/69) having congenital heart disease (CHD) and 18.8% (13/69) having acquired heart disease (AHD) with preserved cardiac function. Among CHD, 10.1% (7/69) had cyanotic CHD and 24.6% (17/769 had acyanotic CHD. Among AHD, 10.1% (7/69) had rheumatic heart disease with preserved cardiac function. Symptomatic systolic heart failure (HF) with ejection fraction <50%, was found in 20.3% (14/69), and pulmonary hypertension was diagnosed in 10.1% (7/69). Overall admission mortality was 5.5% (4/73). Three patients left the hospital against medical advice. None of the patients with systolic HF had CHD. There was no significant association of HIV, gender, or failure to thrive on presence of systolic HF. This is the first report describing the spectrum of pediatric cardiology consults in an inpatient setting in Malawi. There was an unexpectedly high proportion of CHD and systolic HF. Further studies should be conducted to explore the implications and potential causes of these findings.

HIV-infected Children in Malawi Have Decreased Performance on the 6-minute Walk Test With Preserved Cardiac Mechanics Regardless of Antiretroviral Treatment Status.

AIM: The aims of this study were to 1) determine if cardiac disease can be detected in HIV-infected children by strain imaging and 2) to evaluate differences in exercise performance between HIV-infected children on antiretroviral therapy (ART) and HIV-infected children not yet on ART and in HIV-uninfected children by 6-minute walk tests (6MWTs). METHODS: This cross-sectional study evaluated cardiac function by echocardiogram and exercise performance by 6MWT in HIV-infected and HIV-uninfected children 4-18 years of age in Lilongwe, Malawi. Analyses compared HIV uninfected, HIV infected not yet on ART, and HIV infected on ART. Comparisons used χ(2) test, t test, analysis of variance and multiple linear regression. RESULTS: No differences were found in ejection fraction, shortening fraction or strain in 73 children not yet on ART, 149 on ART and 77 HIV-uninfected controls. As viral load increased, children had worse circumferential strain. In addition, children receiving ART had better circumferential strain than those not yet on ART. Increased CD4 percentage was associated with better longitudinal strain and farther 6MWT distance. As longitudinal strain worsened, the 6MWT distance decreased. HIV-infected children not yet on ART walked a mean of 25.8 m less than HIV-uninfected children, and HIV-infected children on ART walked 25.9 m less (P = 0.015 comparing 3 groups). CONCLUSIONS: HIV-uninfected children performed better on the 6MWT than HIV-infected children. Lower viral load, being on ART, and higher CD4 percentage were associated with better strain measures. Better longitudinal strain was associated with a farther 6MWT distance. Overall, ejection fraction, shortening fraction and strain measures between groups were similar, so cardiac strain did not detect cardiac dysfunction in this young population.