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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. 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. 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 [ABSTRACT FROM AUTHOR]

It is a sad reality that although eminently preventable, and despite possessing such knowledge for >70 years, rheumatic heart disease (RHD) remains the most common cause of cardiovascular morbidity and early mortality in young people worldwide. A disease of the poor, RHD is one of the most neglected diseases. Several challenges are unique to the acute rheumatic fever/RHD continuum and contribute to its persistence, including its sequestration among the poorest, its protracted natural history, the erratic availability of penicillin, and the lack of a concerted effort in endemic regions. However, there is cause for optimism following a resurgence in scientific interest over the last 15 years. This review presents the latest advancements in epidemiology, diagnosis, and management. It also discusses pressing research questions on disease pathophysiology, the barriers to implementation of effective management strategies, and pragmatic policy solutions required for translation of current knowledge into meaningful action. [Display omitted] • Rheumatic heart disease is the most common cause of cardiovascular morbidity and early mortality in children and young adults worldwide. • New data on disease burden have driven advancements in diagnosis and management of patients with rheumatic heart disease. • Pragmatic policies are required to translate current knowledge into improved outcomes for patients with rheumatic heart disease. [ABSTRACT FROM AUTHOR]

As longevity has increased for people living with HIV (PLWH) in the United States and Europe, there has been a concomitant increase in the prevalence of cardiovascular disease (CVD) risk factors and morbidity in this population. Whereas the availability of HIV antiretroviral therapy has resulted in dramatic increases in life expectancy in sub-Saharan Africa (SSA), where over two thirds of PLWH reside, if and how these trends impact the epidemiology of CVD is less clear. In this review, we describe the current state of the science on how both HIV and its treatment impact CVD risk factors and outcomes among PLWH in sub-Saharan Africa, including regional factors (unique to SSA) likely to differentiate these relationships from the global North. We then outline how current regional guidelines address CVD prevention among PLWH and which clinical and structural interventions are best poised to confront the co-epidemics of HIV and CVD in the region. We conclude with a discussion of key research gaps that need to be addressed to optimally develop an actionable public health response. [ABSTRACT FROM AUTHOR]

Rheumatic heart disease (RHD) remains a high prevalence condition in low- and middle-income countries. Most individuals with RHD present late, missing the opportunity to benefit from secondary antibiotic prophylaxis. Echocardiographic screening can detect latent RHD, but the impact of secondary prophylaxis in screen-detected individuals is not known.Methods/design: This trial aims to determine if secondary prophylaxis with every-4-week injectable Benzathine penicillin G (BPG) improves outcomes for children diagnosed with latent RHD. This is a randomized controlled trial in consenting children, aged 5 to 17 years in Northern Uganda, confirmed to have borderline RHD or mild definite RHD on echocardiography, according to the 2012 World Heart Federation criteria. Qualifying children will be randomized to every-4-week injectable intramuscular BPG or no medical intervention and followed for a period of 2 years. Ongoing intervention adherence and retention in the trial will be supported through the establishment of peer support groups for participants in the intervention and control arms. A blinded echocardiography adjudication panel consisting of four independent experts will determine the echocardiographic classification at enrollment and trajectory through consensus review. The primary outcome is the proportion of children in the BPG-arm who demonstrate echocardiographic progression of latent RHD compared to those in the control arm. The secondary outcome is the proportion of children in the BPG-arm who demonstrate echocardiographic regression of latent RHD compared to those in the control arm. A sample size of 916 participants will provide 90% power to detect a 50% relative risk reduction assuming a 15% progression in the control group. The planned study duration is from 2018-2021.Discussion: Policy decisions on the role of echocardiographic screening for RHD have stalled because of the lack of evidence of the benefit of secondary prophylaxis. The results of our study will immediately inform the standard of care for children diagnosed with latent RHD and will shape, over 2-3 years, practical and scalable programs that could substantially decrease the burden of RHD in our lifetime.Trial Registration: ClinicalTrials.gov: NCT03346525. Date Registered: November 17, 2017. [ABSTRACT FROM AUTHOR]

Abstract: Cellular transplantation represents a promising therapy for myocardial infarction (MI). However, it is limited by low transplanted cell retention and survival within the ischemic tissue. This study was designed to investigate whether injectable α-cyclodextrin/poly(ethylene glycol)–b-polycaprolactone-(dodecanedioic acid)-polycaprolactone–poly(ethylene glycol) (MPEG–PCL–MPEG) hydrogel could improve cell transplant retention and survival, reduce infarct expansion and inhibit left ventricle (LV) remodeling. Bone marrow-derived stem cells (BMSCs) were encapsulated in α-cyclodextrin/MPEG–PCL–MPEG hydrogel and maintained their morphologies during the cell culturing. MTT assays were used for in vitro cell viability studies of the hydrogel and were shown to be non-cytotoxic. Seven days after MI, 100μl of α-cyclodextrin solution containing 2×107 BMSCs and 100μl of MPEG–PCL–MPEG solution were injected into the infarcted myocardium simultaneously and the solutions solidified immediately. Injection of culture medium or cell alone served as controls. Four weeks after treatment, histological analysis indicated that the hydrogel was absorbed, and the injection of BMSCs with hydrogel had increased cell retention and vessel density around the infarct, and subsequently prevented scar expansion compared with BMSCs injection alone. Echocardiography studies showed that injection of BMSCs with hydrogel increased the LV ejection function and attenuated left ventricular dilatation. This study indicated that the injection of BMSCs with α-cyclodextrin/MPEG–PCL–MPEG hydrogel was an effective strategy which could enhance the effect of cellular transplantation therapy for myocardial infarction. [Copyright &y& Elsevier]

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Summary: Radiofrequency catheter ablation (RFCA) has been increasingly used for the treatment of various kinds of cardiac arrhythmias over the past 20years. RFCA of symptomatic premature ventricular contractions (PVCs) has been reported to be a safe and effective treatment option and may be considered in patients with extremely symptomatic or incapacitating cases who do not respond to medications. Long-term prognosis in patients with truly idiopathic PVCs is excellent, despite frequent recurrences of tachycardia. Sudden death is rare in patients with initially normal left and right ventricular function, in such patients, occult cardiomyopathy is usually identified on postmortem examination. Similarly, progression to diffuse cardiomyopathy is rare. Ablation of PVCs may equal that of supraventricular tachycardia in terms of success rate, safety. These new views will help understand the diagnosis and treatment method for frequent PVCs in patients without heart disease. [Copyright &y& Elsevier]

Summary: Statins and coenzyme Q10 are both used as adjuncts in the treatment of chronic heart failure (CHF) due to their anti-inflammatory and antioxidant effects, respectively. And both have been variously shown to improve cardiac function in patients with CHF. The two agents interact in two ways; statins inhibit coenzyme Q10 synthesis through inhibition of HMG-CoA reductase, the rate limiting step in cholesterol synthesis, also shared by coenzyme Q10. Secondly, they both exhibit their antioxidant effects through activation of the enzyme superoxide dismutase, the rate limiting step in nitric oxide metabolism and main antioxidant mechanism of coenzyme Q10. We hypothesize that the interaction between statins and coenzyme Q10 is more than just a replacement, but a synergistic interaction on superoxide dismutase that could result in better cardiac function, improvement in patient symptoms, shortening of duration of hospital stay and improvement in patient quality of life. [Copyright &y& Elsevier]

In 2012, the World Heart Federation (WHF) published guidelines for the echocardiographic diagnosis of rheumatic heart disease (RHD). This study assesses individual reviewer performance and inter-rater agreement and reliability on the presence of any RHD, as well classification of RHD based on the 2012 WHF criteria. Four cardiologists individually reviewed echocardiograms in the context of a randomized clinical trial (ClinicalTrials.gov : NCT03346525) and participated in a blinded adjudication panel. Panel decision was the reference standard for diagnosis. Performance of individual reviewers to panel adjudication was compared through sensitivity and specificity analyses and inter-rater reliability was assessed between individual panelists using Fleiss free marginal multirater kappa. Echocardiograms from 784 children had two independent reports and panel adjudication. The accuracy of independent reviewers for any RHD had high sensitivity (94%, 95% CI 93–95%) and moderate specificity (62%, 95% CI 53–70%). Sensitivity and specificity for definite RHD was 61.3 (95% CI, 55.3–67.1) and 93.1 (95% CI, 91.6–94.4), with 86.8 (84.7–88.7) and 65.8 (61.0–70.4) for borderline RHD. There was moderate inter-rater agreement (κ = 0.66) on the presence of any RHD while agreement for specific 2012 WHF classification was only fair (κ = 0.51). The 2012 WHF guidelines are moderately reproducible when used by expert cardiologists. More cases of RHD were diagnosed by an consensus panel than by individual reviewers. A revision to the criteria is now warranted to further increase the reliability of the WHF criteria. • Compared to the panel consensus, individuals were less likely to diagnose any RHD, as well as morphological abnormalities. • Inter-rater agreement, even amongst experts, for 2012 WHF classification is fair. • Considerable variability remains amongst reviewers utilizing the WHF criteria. • Our data support the use of a > 2 reviewer system for more diagnosis of RHD. • A revision to the 2012 WHF is now warranted. [ABSTRACT FROM AUTHOR]

• Group A β-hemolytic Streptococcus (GAS) rates seen in Uganda are higher than results pooled globally. • This has implications for primary prevention of GAS. • GAS was universally susceptible to penicillin and trimethoprim–sulfamethoxazole. • Further knowledge of the acute streptococcal pharyngitis burden is essential. Group A β-hemolytic Streptococcus (GAS), also known as Streptococcus pyogenes , is responsible for an annual 600 million cases of acute pharyngitis globally, with 92% of those infections occurring in low-resource settings. Further knowledge of the acute streptococcal pharyngitis burden in low-resource settings is essential if serious post-streptococcal complications – rheumatic fever (RF) and its long-term sequel rheumatic heart disease (RHD) – are to be prevented. Two studies were conducted in school-aged children (5–16 years): a cross-sectional study of streptococcal pharyngeal carriage followed by a prospective cohort study of streptococcal sore throat over 4 weeks from March to April 2017. The cross-sectional study revealed an overall prevalence of GAS carriage of 15.9% (79/496, 95% confidence interval 12.8–19.5%). Among 532 children enrolled in the prospective cohort study, 358 (67%) reported 528 sore throats, with 221 (41.1%) experiencing at least one GAS-positive sore throat. The overall GAS-positive rate for sore throat was 41.8% (221/528). The GAS pharyngeal carriage rates seen in Uganda (15.9%, 95% confidence interval 12.8–19.5%) are higher than the most recent pooled results globally, at 12% (range 6–28%). Additionally, pilot data suggest a substantially higher percentage of sore throat that was GAS-positive (41.8%) compared to pooled global rates when active recruitment is employed. [ABSTRACT FROM AUTHOR]

Background: The J wave has been seen in idiopathic ventricular fibrillation, Brugada syndrome, and early repolarization syndrome. Although these conditions share some ECG features, the clinical consequences are markedly different. J wave presentation in healthy subjects is not a rare phenomenon, although its characteristics are poorly understood. The aim of this study was to investigate the prevalence and the characteristics of the J wave in apparently healthy Chinese adults. Methods: The study was comprised of 1817 consecutive healthy Chinese subjects undergoing annual routine medical examination from April 2006 to July 2006, including 1131 men and 686 women. Routine medical examination including ECG was performed. J wave was defined as a wave on the ECG that followed the QRS complex with amplitude of at least 0.05 mV for 0.03 sec. Results: The prevalence of the J wave in all subjects was 7.26%. The prevalence of the J wave in males was significantly higher than in females (10.52 vs. 1.89%, p <0.01). The incidence of the J wave in the inferior leads (II, III, avF), right precordial leads (V1–V3), and left precordial leads (V4–V6) was 4.57, 0.50, and 2.20%, respectively. The J wave prevalence in the inferior leads was significantly higher than in the left and right precordial leads (both p <0.05). Moreover, the prevalence of the J wave had a positive correlation with age in all subjects (r = 0.78, p <0.01). Conclusions: J wave presentation on the ECG of apparently healthy people is not a rare phenomenon and is more likely to be found in the elderly, in males, and more frequently occurs in the inferior leads than in left and right precordial leads. [Copyright &y& Elsevier]