Severe Rheumatic Heart Disease Research Articles

Handheld echocardiography for the screening and diagnosis of rheumatic heart disease: a systematic review to inform WHO guidelines

Early detection and diagnosis of acute rheumatic fever and rheumatic heart disease are key to preventing progression, and echocardiography has an important diagnostic role. Standard echocardiography might not be feasible in high-prevalence regions due to its high cost, complexity, and time requirement. Handheld echocardiography might be an easy-to-use, low-cost alternative, but its performance in screening for and diagnosing acute rheumatic fever and rheumatic heart disease needs further investigation. In this systematic review and meta-analysis, we searched Embase, MEDLINE, LILACS, and Conference Proceedings Citation Index-Science up to Feb 9, 2024, for studies on the screening and diagnosis of acute rheumatic fever and rheumatic heart disease using handheld echocardiography (index test) or standard echocardiography or auscultation (reference tests) in high-prevalence areas. We included all studies with useable data in which the diagnostic performance of the index test was assessed against a reference test. Data on test accuracy in diagnosing rheumatic heart disease, acute rheumatic fever, or carditis with acute rheumatic fever (primary outcomes) were extracted from published articles or calculated, with authors contacted as necessary. Quality of evidence was appraised using GRADE and QUADAS-2 criteria. We summarised diagnostic accuracy statistics (including sensitivity and specificity) and estimated 95% CIs using a bivariate random-effects model (or univariate random-effects models for analyses including three or fewer studies). Area under the curve (AUC) was calculated from summary receiver operating characteristic curves. Heterogeneity was assessed by visual inspection of plots. This study was registered with PROSPERO (CRD42022344081). Out of 4868 records we identified 11 studies, and two additional reports, comprising 15 578 unique participants. Pooled data showed that handheld echocardiography had high sensitivity (0·87 [95% CI 0·76-0·93]), specificity (0·98 [0·71-1·00]), and overall high accuracy (AUC 0·94 [0·84-1·00]) for diagnosing rheumatic heart disease when compared with standard echocardiography (two studies; moderate certainty of evidence), with better performance for diagnosing definite compared with borderline rheumatic heart disease. High sensitivity (0·79 [0·73-0·84]), specificity (0·85 [0·80-0·89]), and overall accuracy (AUC 0·90 [0·85-0·94]) for screening rheumatic heart disease was observed when pooling data of handheld echocardiography versus standard echocardiography (seven studies; high certainty of evidence). Most studies had a low risk of bias overall. Some heterogeneity was observed for sensitivity and specificity across studies, possibly driven by differences in the prevalence and severity of rheumatic heart disease, and level of training or expertise of non-expert operators. Handheld echocardiography has a high accuracy and diagnostic performance when compared with standard echocardiography for diagnosing and screening of rheumatic heart disease in high-prevalence areas. World Health Organization. For the Chinese, French, Italian, Persian, Portuguese, Spanish and Urdu translations of the abstract see Supplementary Materials section.

Intramuscular versus Enteral Penicillin Prophylaxis to Prevent Progression of Rheumatic Heart Disease: Study protocol for a non-inferiority randomized trial (the GOALIE trial)

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, sub-optimal 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 non-inferiority trial is comparing the efficacy of intramuscular to oral penicillin SAP to prevent progression of mild RHD at 2 years. The Intramuscular versus Enteral Penicillin Prophylaxis to Prevent Progression of Rheumatic Heart Disease (GOALIE) trial is randomizing Ugandan children aged 5-17 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 1004 participants will provide 90% power to demonstrate non-inferiority 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 (Figure 1) summarizes the flow of echocardiographic screening, participant enrollment and follow-up. 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. ClinicalTrials.gov: NCT05693545.

Outcomes of possible and probable rheumatic fever: A cohort study using northern Australian register data, 2013-2019.

In Australia, there is a high burden of acute rheumatic fever (ARF) among Aboriginal and Torres Strait Islander peoples. Clinical diagnostic criteria can result in a diagnosis of 'definite', 'probable' or 'possible' ARF and outcomes range from recovery to severe rheumatic heart disease (RHD). We compared outcomes by ARF diagnosis, where the main outcome was defined as disease progression from: possible to probable ARF, definite ARF or RHD; probable to definite ARF or RHD; or definite ARF to definite ARF recurrence or RHD. Data were extracted from the Northern Territory RHD register for Indigenous Australians with an initial diagnosis of ARF during the 5.5-year study period (01/01/2013-30/06/2019). Descriptive statistics were used to describe cohort characteristics, probability of survival, and cumulative incidence risk of disease progression. Cox proportional hazards regression was used to determine whether time to disease progression differed according to ARF diagnosis. Sub-analyses on RHD outcome, clinical manifestations, and antibiotic adherence were also performed. In total there were 913 cases with an initial ARF diagnosis. Of these, 92 (13%) experienced disease progression. The probability of disease progression significantly differed between ARF diagnoses (p = 0.0043; log rank test). Cumulative incidence risk of disease progression at 5.5 years was 33.6% (95% CI 23.6-46.2) for definite, 13.5% (95% CI 8.8-20.6) for probable and 11.4% (95% CI 6.0-21.3) for possible ARF. Disease progression was 2.19 times more likely in those with definite ARF than those with possible ARF (p = 0.026). Progression to RHD was reported in 52/732 (7%) of ARF cases with normal baseline echocardiography. There was a significantly higher risk of progression from no RHD to RHD if the initial diagnosis was definite compared to possible ARF (p<0.001). These data provide a useful way to stratify risk and guide prognosis for people diagnosed with ARF and can help inform practice.

Potential Role of NT-proBNP and Tissue Doppler Indices to Assess the Severity of Rheumatic Heart Disease: A Cross-sectional Study

Introduction: Rheumatic Heart Disease (RHD) remains the primary cause of acquired Valvular Heart Disease (VHD) in developing countries. The role of Tissue Doppler Indices (TDI) in RHD is understudied. This study aims to fill evidence gaps identified by the American College of Cardiology/American Heart Association in the management of Valvular Heart Disease (VHD) by analysing newer echocardiographic techniques {Tissue Doppler Imaging (TDI)} and biochemical markers (NT-proBNP) against clinical parameters {New York Heart Association (NYHA)} in an understudied patient group. Aim: To evaluate the role of TDI and its association with the functional class of dyspnoea and serum NT-proBNP levels in RHD. Materials and Methods: This cross-sectional study was conducted in the Cardiology and Medicine departments, Central Gujarat, Western India, from January 2021 to June 2022. Fifty-seven consenting adult patients with RHD who underwent echocardiography with Standard Echocardiographic Techniques (SET) to stratify VHD severity were included. Patients were divided into three sub-groups: a) Isolated MR and MR with mild/moderate MS (n=23); b) Isolated MS and MS with mild MR (n=29); and c) Isolated MS and MS with mild or moderate MR (n=48). TDI parameters (e’, a’, e’/a’, and E/e’) at medial mitral, lateral mitral, and tricuspid annuli, NYHA classification, and serum NT-proBNP levels were analysed. The Analysis of Variance (ANOVA) was used to assess the association between NYHA class and clinical and NT-proBNP parameters. The Pearson correlation coefficient was employed to determine linear relationships between NT-proBNP and TDI parameters. Results: The mean age was 45.4±16 years, with the age groups 20-40 years (n=20) and 40-60 years (n=22) having a nearly equal distribution. The female-to-male ratio was 1.48 (34/23). In subgroup C, the a’ velocity decreased from 13.74±3.92 cm/s in NYHA I to 5.17±1.98 cm/s in NYHA IV (p=0.0312), and the e’/a’ ratio increased from 0.96±0.40 in NYHA I to 2.41±1.00 in NYHA IV (p=0.0210). These changes paralleled trends in a’ value (p=0.0306) and e’/a’ ratio (p=0.0157) with increasing NTproBNP levels. Conclusion: At the tricuspid annulus, the e’/a’ ratio and a’ velocity can complement NT-proBNP in cases where there is a discrepancy between the clinical status of the patient and the severity of the valve lesion as determined by SET. Larger-scale studies are needed to further evaluate the association between TDI parameters and long-term clinical outcomes, as well as to identify the optimal timing for surgical intervention in RHD patients.

Left ventricular remodelling in rheumatic heart disease – trends over time and implications for follow-up in childhood

BackgroundRheumatic heart disease (RHD) is the most common form of acquired heart disease worldwide. In RHD, volume loading from mitral regurgitation leads to left ventricular (LV) dilatation, increased wall stress, and ultimately LV dysfunction. Improved understanding of LV dynamics may contribute to refined timing of intervention. We aimed to characterize and compare left ventricular remodelling between rheumatic heart disease (RHD) severity groups by way of serial echocardiographic assessment of volumes and function in children.MethodsChildren with RHD referred to Perth Children’s Hospital (formally Princess Margaret Hospital) (1987–2020) were reviewed. Patients with longitudinal pre-operative echocardiograms at diagnosis, approximately 12 months and at most recent follow-up, were included and stratified into RHD severity groups. Left ventricular (LV) echocardiographic parameters were assessed. Adjusted linear mixed effect models were used to compare interval changes.Results146 patients (median age 10 years, IQR 6–14 years) with available longitudinal echocardiograms were analysed. Eighty-five (58.2%) patients had mild, 33 (22.6%) moderate and 28 (19.2%) severe RHD at diagnosis. Mean duration of follow-up was 4.6 years from the initial diagnosis. Severe RHD patients had significantly increased end-systolic volumes (ESV) and end-diastolic volumes (EDV) compared to mild/moderate groups at diagnosis (severe versus mild EDV mean difference 27.05 ml/m2, p < 0.001, severe versus moderate EDV mean difference 14.95 ml/m2, p = 0.006). Mild and moderate groups experienced no significant progression of changes in volume measures. In severe RHD, LV dilatation worsened over time. All groups had preserved cardiac function.ConclusionsIn mild and moderate RHD, the lack of progression of valvular regurgitation and ventricular dimensions suggest a stable longer-term course. Significant LV remodelling occurred at baseline in severe RHD with progression of LV dilatation over time. LV function was preserved across all groups. Our findings may guide clinicians in deciding the frequency and timing of follow-up and may be of clinical utility during further reiterations of the Australia and New Zealand RHD Guidelines.

Health Related Quality of Life of Ugandan Children Following Valve Replacement Surgery for Rheumatic Heart Disease.

Valve replacement surgery (VRS) improves clinical outcomes in patients with severe rheumatic heart disease (RHD). However, lifelong anticoagulation and frequent monitoring are required, which potentially impacts health-related quality of life (HRQoL). In this study, we assessed the HRQoL of people with RHD in Uganda following VRS. This was a hospital-based, cross-sectional study conducted between March and August 2021. Eligible participants were individuals who had VRS before the age of 18 years. The Pediatric Quality of Life Inventory-Cardiac Module (PedsQL-Cardiac module) was used to evaluate HRQoL. A total mean score of ≥ 80% was considered as optimal HRQoL. Of the 83 eligible participants, 52 (60.5%) were female, with a median age of 18 (interquartile range: 14-22) years. Most participants had NYHA I functional status (n = 79, 92%). Most (n = 73, 92.4%) surgeries were performed outside of Uganda, and 61 (72.6%) were single mechanical valve replacement. Almost half (n = 45, 54%) expressed no concern about being on life-long warfarin therapy. However, 24 (29.3%) feared bleeding. The optimal mean score of cardiac-specific HRQoL was achieved in 50 (60.2%) of participants. Factors associated with optimal HRQoL were body mass index (BMI) (adjusted odds ratio (aOR), 1.2, 95% Confidence Interval: 1.1-1.3, p = 0.006), being afraid of bleeding or bruising (aOR: 1.5, 95% CI: 1.21-2.47, p = 0.004), acceptance of having an artificial valve (aOR: 2.7, 95% CI; 1.64-3.81, p < 0.001). HRQoL was optimal in about three in five participants following VRS. Increasing BMI and acceptance of artificial valve were significantly associated with optimal HRQoL.

Contemporary Specialist Care for Rheumatic Heart Disease Meets New Zealand Heart Foundation Recommendations for Most Patients in Tāmaki Makaurau

The World Health Organization endorses registries as a valuable adjunct to managing rheumatic heart disease (RHD). This study evaluated the management of New Zealand RHD Registry patients from 2010 to 2019 and alignment to New Zealand Heart Foundation Guidelines. A retrospective audit was undertaken of 150 patients in Tāmaki Makaurau, randomly selected from the New Zealand RHD Registry, with a review of frequency of specialist follow-up and echocardiograms, documentation regarding benzathine penicillin G, dental care, and anticoagulation post-surgery. There were 61 individuals with moderate RHD and 89 with severe RHD. Follow-up data were available for 128 of 150 (85%) patients who attended one or more specialist appointment. Of these, median duration between specialist appointments was 14 months and 8 months for moderate and severe, respectively (range to 8 years). Mean duration between echocardiograms was 21 months and 12 months for moderate and severe, respectively. Benzathine penicillin G prophylaxis was documented in 95 of 150 (63%) clinic letters and dental care was discussed in 99 of 150 (66%). Among 46 patients on warfarin, 13 (39%) had one or more hospitalisations due to INR control, bleeding, or thrombosis. The interval between specialist appointments and echocardiograms in patients with RHD in Auckland conforms with best practice guidelines; however, the wide range and the 15% with no documented follow-up highlight that some patients are not being seen at timely intervals. Benzathine penicillin G prophylaxis and dental treatment were discussed at most clinic appointments. Hospitalisation for anticoagulation complications occurred in nearly 40% of those on warfarin, highlighting the need for improved anticoagulation services for individuals following mechanical valve surgery.

Global economic burden per episode for multiple diseases caused by group A Streptococcus

Considering the lack of existing evidence on economic burden for diseases caused by group A Streptococcus, we estimated the economic burden per episode for selected diseases. Each cost component of direct medical costs (DMCs), direct non-medical costs (DNMCs), and indirect costs (ICs) was separately extrapolated and aggregated to estimate the economic burden per episode by income group as classified by the World Bank. Adjustment factors for DMC and DNMC were generated to overcome related data insufficiencies. To address uncertainty surrounding input parameters, a probabilistic multivariate sensitivity was carried out. The average economic burden per episode ranged from $22 to $392 for pharyngitis, $25 to $2,903 for impetigo, $47 to $2,725 for cellulitis, $662 to $34,330 for invasive and toxin-mediated infections, $231 to $6,332 for acute rheumatic fever (ARF), $449 to $11,717 for rheumatic heart disease (RHD), and $949 to $39,560 for severe RHD across income groups. The economic burden for multiple Group A Streptococcus diseases underscores an urgent need to develop effective prevention strategies including vaccines.

A Retrospective Study on Drug and Dietary Patterns in Patients With Severe Rheumatic Valvular Heart Disease in Eastern India.

Background India has a high prevalence of rheumatic valvular heart diseases. Empirical treatment in rheumatic heart disease curtails morbidity and mortality. Less is known about the drug and dietary management of severe rheumatic heart disease at the pretertiary care level, which forms the building stone in the management of rheumatic heart disease. The present study was carried out to evaluate the drug and dietary patterns of patients with severe rheumatic valvular heart disease at a pretertiary care level, which is the backbone of the management of rheumatic heart disease. Methodology This cross-sectional study was carried out in a tertiary care center in Eastern India between May 2020 and May 2022 across 1,264 study subjects. The drug and dietary patterns of the patients with severe rheumatic valvular heart disease during their index visit to the cardiac department were studied and analyzed.Patients aged less than 18 years; patients with mild or moderate rheumatic valvular heart diseases; patients with coexisting end-stage organ disease (chronic liver disease and chronic kidney disease), malignancy, and sepsis; and patients not willing to participate in the study were excluded. Results Most of the patients were on diuretic therapy, and diuretic therapy was overprescribed across the patients with mitral regurgitation, aortic stenosis, and aortic regurgitation. Most of the patients across each spectrum of rheumatic valvular heart disease were lacking the cornerstone therapy such as beta-blockers in mitral stenosis and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in mitral and aortic regurgitation. The recommended injectable benzathine penicillin prophylaxis was prescribed in a very small number of patients (5%), and most of the patients were on oral penicillin prophylaxis (95%) in spite of its reportedhigh failure rate in prophylaxis. Empirical rationale prescriptions in severe rheumatic valvular heart disease were lacking in the pretertiary care level in Eastern India. Conclusion Each spectrum of severe valvular heart disease was lacking the cornerstone therapy such as beta-blockers in mitral stenosis and ACE inhibitors or angiotensin receptor blockers (ARBs) in mitral and aortic regurgitation along with recommended injectable benzathine penicillin prophylaxis. Diuretics and digoxin were overprescribed across the spectrum of rheumatic heart disease. Improvement of this essential gap in the treatment of severe rheumatic heart disease would bring down morbidity and improve mortality in the future.

Does Secondary Antibiotic Prophylaxis Improve Clinical Outcomes in Adult Rheumatic Heart Disease Patients Post-Valve Replacement?

Secondary prevention of recurrent rheumatic fever in individuals with rheumatic heart disease (RHD) requires continuous antibiotic prophylaxis. However, the impact of antibiotic prophylaxis on the outcome of patients with severe RHD who underwent heart valve replacement is unknown. The objective of the study was to assess the relationship between the use of antibiotics as secondary prophylaxis in RHD patients who underwent valve replacement and clinical outcomes including mortality, reoperation, and valve-related hospitalization. We retrospectively compared outcomes of adult patients who underwent heart valve replacement for RHD at our institution from 1990 through 2014 and who received secondary antibiotic prophylaxis (prophylaxis group) with those who did not receive prophylaxis (nonprophylaxis group) using propensity score matching analysis. A total of 1094 patients (56% females, median age 40 years, range 31-53 years) were included with a median follow-up of 9.6 years (range 2.9-12.6 years). Antibiotic prophylaxis was prescribed in 201 patients (18%). Propensity score matching analysis demonstrated no significant difference in overall survival (95% [92%-98%] vs 97% [95%-99%], respectively; P = .7), valve-related hospitalization-independent survival (72% [range 65%-78%] vs 81% [range 76%-88%]; P = .25), and redo valve surgery-independent survival [76% [range 70%-83%] vs 75% [range 72%-79%]; P = .41) at 10-year follow-up in the nonantibiotic prophylaxis versus the antibiotic prophylaxis group. Secondary antibiotic prophylaxis among adult RHD patients following valve replacement is not associated with improved clinical outcomes.

Cohort profile: methodology and cohort characteristics of the Aotearoa New Zealand Rheumatic Heart Disease Registry

PurposeTo create a cohort with high specificity for moderate and severe rheumatic heart disease (RHD) in New Zealand, not reliant on International Classification of Diseases discharge coding. To describe the...

Alpha-1-antitrypsin in serum exosomes and pericardial fluid exosomes is associated with severity of rheumatic heart disease.

Rheumatic heart disease (RHD) is an autoimmune sequel of pharyngitis and rheumatic fever that leads to permanent heart valve damage, especially the mitral valves. The mitral valves, which are responsible for the binding of auto-antibodies during immune response generation, lead to valve scarring and eventually valves dysfunction. Recently, exosomes (EXOs), the nano-sized vesicles, which range in size from 30 to 150nm, are reported in various cardiovascular physiological and pathological processes. These vesicles are found in several body fluids such as plasma, serum, and also in cell culture media. Exosomal cargo contains proteins, which are taken up by the recipient cells and modulate the cellular characteristics. The role of exosomal proteins in RHD is still obscure. Hence, the present study has been designed to unveil the exosomal proteins in disease severity during RHD. In this study, the exosomes were isolated from biological fluids (serum and pericardial fluid) of RHD patients as well as from their respective controls. Protein profiling of these isolated exosomes revealed that alpha-1 antitrypsin is up-regulated in the biological fluids of RHD patients. The enhanced levels of exosomal alpha-1 antitrypsin, were further, validated in biological samples and mitral valve tissues of RHD patients, to correlate with the disease severity. These findings suggest an association of increased levels of exosomal alpha-1 antitrypsin with the RHD pathogenesis.

An empirical study on factors responsible for Rheumatic Heart Disease (RHD) and its severity levels amongst the Bhutanese populace

Background and objectives: This paper is aimed at excavating the factors responsible for RHD events and vis-à-vis establishing severity levels of RHD patients referred to Jigme Dorji Wangchuck National Referral Hospital (JDWNRH) in Thimphu’s capital city of Bhutan. Methods: By taking notorious advantage of the data gathered over the past five years (2016-2020) from RHD patients across 20 districts of Bhutan, about 232 RHD patients are involved in this study recorded in JDWNRH by the Cardiology Department. Besides descriptive methods, multivariate linear regression models augmented by the multinomial logistic regression models had been applied to establish the causual links. Results: The findings revealed that RHD prevailed amongst the young populace of Bhutan, especially females. Variables like age, frequency of visits, number of diagnostics, levels of education and region had been found as predictors of RHD prevalence. Other socio-demographic factors like occupation and status of employment did not affect the RHD prevalence. The multinomial logistic regression results indicated that higher levels of education as an important factor for not making the patient fall into the category of ‘severe.’ Age has been constantly found to be a highly significant variable contributing to RHD events and a quadratic relationship is revealed between age and the severity of RHD. Conclusion and implications for translation: This study pigeonholed the significant factors responsible for RHD events and entailed severity levels by gender and age. The findings of this study also provide additional important insights into developing public health policies and programs.

Neurological and Psychiatric Disorders in Patients with Rheumatic Heart Disease: Unveiling what is Beyond Cardiac Manifestations.

Background:Rheumatic heart disease (RHD) is the most serious manifestation of rheumatic fever, which may also affect the brain. The current study assessed the prevalence of neuropsychiatric manifestations in patients with RHD, including clinical features associated with basal ganglia motor dysfunction (BGMD).Methods:We conducted neurologic and psychiatric assessments in consecutive patients with RHD referred to a tertiary center for heart valve diseases. Echocardiography was performed to assess the pattern of valvular involvement and RHD severity. Validated questionnaires for the evaluation of cognition, depression, anxiety, and obsessive-compulsive symptoms (OCS) were applied. BGMD was clinically defined by the presence of hyperkinetic movement disorders.Results:Fifty patients with age of 43.2 ± 10.8 years, 84% female, were included. Mitral valve was affected in 47 patients (94%), and 21 of them (42%) also had aortic valve involvement. Chorea (22%), chronic tics (18%), OCS (48%), major depression (34%), generalized anxiety disorder (54%), cognitive complaints (66%), migraine (52%) and seizures (18%) were frequently reported. The factors associated with BGMD were age (p = 0.018), major depression (p = 0.013), and Yale-Brown Obsessive Compulsive (Y-BOCS) score (p = 0.011). The severity of heart disease was not associated with BGMD.Conclusions:Neuropsychiatric manifestations are frequent in RHD patients, which may persist up to three decades after acute rheumatic fever. Age, major depression and severity of OCS were independently associated with BGMD. These manifestations deserve a close attention of clinicians and researchers dealing with adult patients with RHD.

Medium-term outcomes from mitral valve surgery for rheumatic heart disease in young adults in Aotearoa New Zealand: a cohort study.

Rheumatic heart disease (RHD) remains an important cause of morbidity and mortality in New Zealand. Factors associated with the choice of surgical treatment for advanced RHD in young adults are poorly understood. We sought to review our local experience with the surgical management of young adults with rheumatic mitral valvular disease. From 2003 to 2016, all patients aged 15-24 years undergoing mitral valve surgery for rheumatic disease at Auckland City Hospital, New Zealand were retrospectively reviewed. During the 13-year study period, 73 young adults underwent mitral surgery; 85% were Maori or Pacific Islanders. Mitral repair was performed in 32 patients and replacement in 41 patients. Isolated mitral valve surgery was performed in 36%, double valve procedures in 47%, and triple valve procedures in 17% of patients. The 30-day mortality rate and stroke rate were 1.4% and 2.7% respectively. The medium-term mortality rate was 11.9% across a mean follow-up of 6 years (6.9% in the repair group, 15.8% in the replacement group, p=0.25). There were increased bleeding complications (p=0.04) in patients with mechanical mitral valve replacement. For patients on warfarin, across medium-term follow-up, the INR was in the therapeutic range only 23% of the time. Most young adults in New Zealand with severe RHD requiring surgery are of indigenous Maori or Pacific Island ethnicity. There is a trend towards improved survival with mitral repair. There is a significant tendency towards increased bleeding complications in patients on warfarin for mechanical mitral replacement. Warfarin compliance is poor.

Data-independent acquisition mass spectrometry in severe rheumatic heart disease (RHD) identifies a proteomic signature showing ongoing inflammation and effectively classifying RHD cases

BackgroundRheumatic heart disease (RHD) remains a major source of morbidity and mortality in developing countries. A deeper insight into the pathogenetic mechanisms underlying RHD could provide opportunities for drug repurposing, guide recommendations for secondary penicillin prophylaxis, and/or inform development of near-patient diagnostics.MethodsWe performed quantitative proteomics using Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectrometry (SWATH-MS) to screen protein expression in 215 African patients with severe RHD, and 230 controls. We applied a machine learning (ML) approach to feature selection among the 366 proteins quantifiable in at least 40% of samples, using the Boruta wrapper algorithm. The case–control differences and contribution to Area Under the Receiver Operating Curve (AUC) for each of the 56 proteins identified by the Boruta algorithm were calculated by Logistic Regression adjusted for age, sex and BMI. Biological pathways and functions enriched for proteins were identified using ClueGo pathway analyses.ResultsAdiponectin, complement component C7 and fibulin-1, a component of heart valve matrix, were significantly higher in cases when compared with controls. Ficolin-3, a protein with calcium-independent lectin activity that activates the complement pathway, was lower in cases than controls. The top six biomarkers from the Boruta analyses conferred an AUC of 0.90 indicating excellent discriminatory capacity between RHD cases and controls.ConclusionsThese results support the presence of an ongoing inflammatory response in RHD, at a time when severe valve disease has developed, and distant from previous episodes of acute rheumatic fever. This biomarker signature could have potential utility in recognizing different degrees of ongoing inflammation in RHD patients, which may, in turn, be related to prognostic severity.

Clinical outcomes of children with rheumatic heart disease

ObjectiveTo evaluate the long-term clinical outcomes of children with rheumatic heart disease (RHD) in Uganda, and determine characteristics that predict adverse outcomes.MethodsThis retrospective cohort study evaluated the risk of death...

Secondary prevention of rheumatic heart disease in Ethiopia: a multicenter study

BackgroundEthiopia has a high acute rheumatic fever (ARF) and rheumatic heart disease (RHD) prevalence, and to our knowledge, there are no data on the status of secondary prevention in children with RHD. This study describes the status of secondary RHD prevention.MethodsA multicenter, prospective study was performed on children aged 5–17 years with RHD in Ethiopia. Good adherence was defined as at least 80% completion of benzathine penicillin (BPG) or oral Amoxicillin within the previous year. The primary outcome measure was adherence to prophylaxis, expressed as a proportion. Socio-demographics, severity of RHD, and ARF recurrence were evaluated.ResultsA total of 337 children with a mean age of 12.9 ± 2.6 years were included. The majority (73%) had severe aortic/mitral disease. Participants were on BPG (80%) or Amoxicillin (20%) prophylaxis. Female sex (P = 0.04) use of BPG (0.03) and shorter mean duration of prophylaxis in months (48.5 ± 31.5 vs. 60.7 ± 33, respectively, P < 0.008) predicted good adherence. Running out of medications (35%), interrupted follow-up (27%), and the COVID-19 pandemic (26%) were the most common reasons for missing prophylaxis. Recurrence of ARF was higher in participants on Amoxicillin compared with BPG (40% vs. 16%, P < 0.001) and in those with poor adherence compared with good adherence (36.8% vs. 17.9%, respectively, P = 0.005). Type and duration of prophylaxis (OR 0.5, CI = 0.24, 0.9, P = 0.02; OR = 1.1, CI = 1.1, 1.2, P = 0.04, respectively), and sex (OR = 1.9, CI = 1.1, 3.4, P = 0.03) were independent predictors of poor adherence.ConclusionPoor adherence is prevalent in Ethiopian children living with RHD. Amoxicillin is a suboptimal option for prophylaxis as its use is associated with lower adherence and a higher rate of ARF recurrence.

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.

Pediatric Rheumatic Heart Disease in a Middle-Income Country: A Population-Based Study.

Rheumatic heart disease (RHD), a debilitating complication from rheumatic fever, remains a problem in low- and middle-income countries. This study describes the incidence, prevalence, modifiable risk factors for severe RHD and immediate outcome of pediatric RHD. This population-based and observational cohort study reviewed pediatric RHD patients (0-18 years) from the Sabah Pediatric Rheumatic Heart Registry from 2015 till 2018. A total of 188 RHD were reviewed with 120 new cases. The incidence of RHD is 2.19 [95% confidence interval (CI): 1.83-2.61] per 100 000 population, with a rising trend over time. Meanwhile, the prevalence of RHD was 13.78 (95% CI: 11.92-15.86) per 100 000 pediatric population. The majority of patients were from indigenous groups (59.0%), male (56.4%) with a mean age of 14.3 (3.31) years. About 77.9% had the lowest household income, and a significant proportion lived in overcrowded conditions. At diagnosis, 59% were diagnosed with severe RHD. There is heightened risk but no statistical significance between modifiable factors (low weight and height percentile at diagnosis, lowest income group, renting a house, overcrowding and healthcare access of more than 5 km) with severe RHD. Severe RHD is significantly associated with risk for intervention (p = 0.016). Sixteen (13.8%) patients required surgical intervention. About 97.6% of patients were on intramuscular benzathine penicillin G with 84.5% compliance. The rising prevalence and incidence of pediatric RHD in Sabah, with the most being severe RHD at diagnosis, necessitates the development of an echocardiographic screening and a comprehensive national disease program.