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.

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.

Octreotide improves human lymphatic fluid transport a translational trial.

OBJECTIVES: Chylothorax is a complex condition and many different pharmacological agents have been tried as treatment. Octreotide is used off-label to treat chylothorax, but the efficacy of octreotide remains unclear. A decrease in lymph production is suggested as the mechanism. In this cross-over study, we explore the direct effect of octreotide on human lymphatic drainage. METHODS: Pre-clinical: the effect of octreotide on force generation was assessed during acute and prolonged drug incubation on human lymphatic vessels mounted in a myograph. Clinical: in a double-blinded, randomized, cross-over trial including 16 healthy adults, we administered either octreotide or saline as an intravenous infusion for 2.5 h. Near-infrared fluorescence imaging was used to examine spontaneous lymphatic contractions and lymph pressure in peripheral lymphatic vessels and plethysmography was performed to assess the capillary filtration rate, capillary filtration coefficient and isovolumetric pressures of the lower leg. RESULTS: Pre-clinical: human thoracic duct (n = 12) contraction rate was concentration-dependently stimulated by octreotide with a maximum effect at 10 and 100 nmol/l in the myograph chamber. Clinical: spontaneous lymphatic contractions and lymph pressure evaluated by near-infrared fluorescence did not differ between octreotide or placebo (P = 0.36). Plethysmography revealed similar capillary filtration coefficients (P = 0.057), but almost a doubling of the isovolumetric pressures (P = 0.005) during octreotide infusion. CONCLUSIONS: Octreotide stimulated lymphatic contractility in the pre-clinical setup but did not affect the spontaneous lymphatic contractions or lymph pressure in healthy individuals. Plethysmography revealed a doubling in the isovolumetric pressure. These results suggest that octreotide increases lymphatic drainage capacity in situations with high lymphatic afterload.

Leveraging School Health Programs in Africa: Integrated Screening for Rheumatic Heart Disease and Dental Caries.

Background: Rheumatic heart disease (RHD) and dental caries (DC) disproportionately affect children and young adults in sub-Saharan countries, with major impact on schoolchildren's health and education. DC in children with RHD constitutes an important risk for fatal complications. Our study aimed at assessing the feasibility of simultaneous RHD and DC screening in school environment. Methods: March 20-24, 2022, we performed an observational descriptive study of schoolchildren in a public school in Maputo City, Mozambique. RHD screening involved two stages: first, a physical examination (including cardiac auscultation and direct observation of the oral cavity), and second, an abbreviated echocardiography performed by a cardiologist. Rapid testing for group A Streptococcus (GAS) was done to every eighth child in the classroom and for those with signs suggesting recent infection, in accordance with the study protocol developed for screening. A multidisciplinary team collected the data. Data were analyzed using descriptive statistics. Findings: A total of 954 students (median age 9; range 6-15) were screened. One hundred and twenty-five participants were eligible for a rapid antigen test, of which 6 (4.8%) tested positive. On clinical evaluation 52 children (5.3%) presented a heart murmur. Echocardiography on 362 children showed borderline RHD in 35 children and definite RHD in 2 (0.6%); 1 child had a ventricular septal defect. Dental cavities were present in 444 (48.4%), despite 904 out of 917 students reporting brushing of their teeth once to three times daily (98.6%). Conclusion: School-based integrated oral and cardiovascular screenings and use of rapid tests for GAS carriage provide crucial information to create customized preventive strategies for rheumatic fever (RF) and RHD in low- and middle-income countries (LMICs), in addition to detecting children at very high risk of bacterial endocarditis. The sustainability of such interventions and acceptability by health providers needs to be assessed.

The transport function of the human lymphatic system-A systematic review.

Physiological properties and function of the lymphatic system is still somewhat of a mystery. We report the current knowledge about human lymphatic vessel contractility and capability of adaptation. A literature search in PubMed identified studies published January 2000-September 2022. Inclusion criteria were studies investigating parameters related to contraction frequency, fluid velocity, and lymphatic pressure in vivo and ex vivo in human lymphatic vessels. The search returned 2885 papers of which 28 met the inclusion criteria. In vivo vessels revealed baseline contraction frequencies between 0.2 ± 0.2 and 1.8 ± 0.1 min1 , velocities between 0.008 ± 0.002 and 2.3 ± 0.3 cm/s, and pressures between 4.5 (range 0.5-9.2) and 60.3 ± 2.8 mm Hg. Gravitational forces, hyperthermia, and treatment with nifedipine caused increases in contraction frequency. Ex vivo lymphatic vessels displayed contraction frequencies between 1.2 ± 0.1 and 5.5 ± 1.2 min-1 . Exposure to agents affecting cation and anion channels, adrenoceptors, HCN channels, and changes in diameter-tension properties all resulted in changes in functional parameters as known from the blood vascular system. We find that the lymphatic system is dynamic and adaptable. Different investigative methods yields alternating results. Systematic approaches, consensus on investigative methods, and larger studies are needed to fully understand lymphatic transport and apply this in a clinical context.

Association between nutritional status and socio-economic status among school children aged 9-17 years in a semi-urban area of Nepal.

BACKGROUND: In many low-and middle-income countries (LMICs), childhood overweight is increasing, while underweight remains a problem. This study aimed to investigate the association between socio-economic status (SES) and nutritional status among Nepalese school children. METHODS: This cross-sectional study used a multistage random cluster sampling method and included 868 students aged 9-17 years from both public and private schools located in a semi-urban area of Pokhara Metropolitan City, Nepal. SES was determined based on a self-reported questionnaire. Body weight and height were measured by health professionals and body mass index (BMI) was categorized based on the World Health Organization BMI-for-age cut-offs. The association between Lower and Upper SES and BMI was assessed using mixed-effects logistic regression model estimating the adjusted odds ratio (aOR) with a corresponding 95% confidence interval (CI) and compared to Middle SES. RESULTS: The proportion of obesity, overweight, underweight, and stunting among school children was 4%, 12%, 7%, and 17%, respectively. More girls were overweight/obese compared with boys (20% vs. 13%). The mixed-effects logistic regression model showed that both participants from Lower SES households and Upper SES households had a higher tendency to be overweight compared to participants from Middle SES; aOR = 1.4; 95% CI 0.7-3.1 and aOR = 1.1; 95% CI 0.6-2.1, respectively. Furthermore, stunting and overweight occurred simultaneously. CONCLUSIONS: This study found that about one out of four children and adolescents in the study setting was malnourished. There was a tendency that both participants from Lower SES and Upper SES had higher odds of being overweight compared to participants from Middle SES. Furthermore, both stunting and overweight were present simultaneously in some individuals. This emphasizes the complexity and importance of awareness of childhood malnutrition in LMICs like Nepal.

[Plastic bronchitis].

Plastic bronchitis (PB) is a rare disease caused by abnormal lymphatic vessels in the thorax. These vessels drain into the bronchi creating solid casts and potential life-threatening airway obstruction. This is a case report of a 30-year-old man diagnosed with PB after several years of extensive examinations due to symptoms misconceived as non-allergic asthma. We describe the first interventional treatment in Denmark using special T2 weighed MR imaging and dynamic contrast MR lymphangiography with subsequent embolisation of abnormal lymphatic vessels in the thorax.

Plastic Bronchitis and Protein-Losing Enteropathy in the Fontan Patient: Evolving Understanding and Emerging Therapies.

Plastic bronchitis (PB) and protein-losing enteropathy (PLE) are rare but potentially devastating complications of the Fontan circulation. PB occurs in ∼4% of Fontan patients, typically presents within 2 to 3 years of Fontan completion with chronic cough, wheezing, fever, or acute asphyxiation, and is characterised by proteinaceous airway casts that are expectorated or found on bronchoscopy. PLE develops in 4% to 13% of patients, usually within 5 to 10 years post Fontan, and manifests with edema, ascites, hypoalbuminemia, lymphopenia, hypogammaglobulinemia, and elevated fecal alpha-1 antitrypsin 1. These disorders have similar pathophysiology involving disruption of the lymphatic system resulting from elevated central venous pressure combined with elevated lymphatic production and inflammation, resulting in lymphatic drainage into low-pressure circuits such as the airways (PB) and duodenum (PLE). Our understanding of these disorders has greatly improved over the past decade as a result of advances in imaging of the lymphatic system through magnetic resonance lymphangiography and early success with lymphatic interventions including lymphatic embolisation, thoracic duct embolisation, and percutaneous thoracic duct decompression. Both PB and PLE require a multidisciplinary approach that addresses and optimises residual hemodynamic lesions through catheter-based intervention, lowers central venous pressure through medical therapy, minimises symptoms, and targets abnormal lymphatic perfusion when symptoms persist. This review summarises the pathophysiology of these disorders and the current evidence base regarding management, proposes treatment algorithms, and identifies future research opportunities. Key considerations regarding the development of a lymphatic intervention program are also highlighted.

Evaluating Vitamin D levels in Rheumatic Heart Disease patients and matched controls: A case-control study from Nepal.

BACKGROUND: Diagnosis and treatment for Rheumatic Heart Disease (RHD) is inaccessible for many of the 33 million people in low and middle income countries living with this disease. More knowledge about risk factors and pathophysiologic mechanisms involved is needed in order to prevent disease and optimize treatment. This study investigated risk factors in a Nepalese population, with a special focus on Vitamin D deficiency because of its immunomodulatory effects. METHODS: Ninety-nine patients with confirmed RHD diagnosis and 97 matched, cardiac-healthy controls selected by echocardiography were recruited from hospitals in the Central and Western region of Nepal. Serum 25(OH)D concentrations were assessed using dried blood spots and anthropometric values measured to evaluate nutritional status. Conditional logistic regression analysis was used to define association between vitamin D deficiency and RHD. RESULTS: The mean age of RHD patients was 31 years (range 9-70) and for healthy controls 32 years (range 9-65), with a 4:1 female to male ratio. Vitamin D levels were lower than expected in both RDH and controls. RHD patients had lower vitamin D levels than controls with a mean s-25(OH)D concentration of 39 nmol/l (range 8.7-89.4) compared with controls 45 nmol/l (range 14.5-86.7) (p-value = 0.02). People with Vitamin D insufficiency had a higher risk (OR = 2.59; 95% CI: 1.04-6.50) of also having RHD compared to people with Vitamin D concentrations >50 nmol/l. Body mass index was significantly lower in RHD patients (22.6; 95% CI, 21.5-23.2) compared to controls (24.2; 95% CI, 23.3-25.1). CONCLUSION: RHD patients in Nepal have lower Vitamin D levels and overall poor nutritional status compared to the non-RHD controls. Longitudinal studies are needed to explore the causality between RHD and vitamin D level. Future research is also recommended among Nepali general population to confirm the low level of vitamin D as reported in our control group.

Mid-upper arm circumference as an indicator of underweight in adults: a cross-sectional study from Nepal.

BACKGROUND: Undernourished people have an increased risk of premature mortality from both infectious and non-communicable diseases. Aside from screening purposes, assessment of nutritional status is a useful tool in management and evaluation of various chronic diseases. Body-Mass-Index (BMI) is today the most commonly used marker of nutritional status however, this method presents a challenge in many low resource settings and immobile patients. Mid-upper arm circumference (MUAC) is another anthropometric measure that requires minimal equipment and little training. So far, MUAC cutoffs for undernutrition are well established in children < 5 years but there is still no consensus for a specific cutoff in adults. The objective of this study was to compare MUAC with BMI and suggest a MUAC cut-off corresponding to a BMI of 18.5 kg/m2 to identify underweight in adults. METHODS: A cross-sectional study was conducted at two urban public hospitals in Nepal. The following variables where collected: MUAC, weight, height, sex, age and self-reported medical history. EXCLUSION CRITERIA: < 19 years of age, pregnancy and oedema. Sensitivity and specificity for a MUAC value corresponding to BMI < 18.5 was calculated. ROC analysis was performed for male and female as well as Pearson's correlation of MUAC and BMI. RESULTS: A total of 302 people between 18 and 86 years of age, 197 women and 105 men, were included. Of these, 90 people suffered from rheumatic heart disease. MUAC was highly correlated with BMI in both women r = 0.889 and men r = 0.846. Best statistically derived MUAC cutoff corresponding to a BMI < 18.5 kg/m2 was 24.5 cm (Youdens Index = 0.75; sensitivity 92.86; specificity 82.48), with high predictive value (AUROCC> 0.9). The setting based optimal MUAC cutoff was also 24.5 cm. No considerable variation was found in sex- and disease specific subgroups. CONCLUSION: MUAC is strongly correlated with BMI in adults in Nepal. For simplicity, a MUAC of 24.5 cm is the optimal statistically and setting based cutoff in both women and men to identify underweight (BMI < 18.5 kg/m2).

Ivabradine: Current and Future Treatment of Heart Failure.

In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end-diastolic pressure. Current treatments for HF with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT1 ) antagonists, ß-adrenoceptor antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT1 receptor antagonist and neprilysin inhibitor. In HF, the risk of readmission for hospital and mortality is markedly higher with a heart rate (HR) above 70 bpm. Here, we review the evidence regarding the use of ivabradine for lowering HR in HF. Ivabradine is a blocker of an I funny current (I(f)) channel and causes rate-dependent inhibition of the pacemaker activity in the sinoatrial node. In clinical trials of HFrEF, treatment with ivabradine seems to improve clinical outcome, for example improved ejection fraction (EF) and less readmission for hospital, but the effect appears most pronounced in patients with HRs above 70 bpm, while the effect on cardiovascular death appears less consistent. The adverse effects of ivabradine include bradycardia, atrial fibrillation and visual disturbances, but ivabradine avoids the negative inotrope effects observed with ß-adrenoceptor antagonists. In conclusion, in patients with stable HFrEF with EF<35% and HR above 70 bpm, ivabradine improves the outcome and might be a first choice of therapy, if beta-adrenoceptor antagonists are not tolerated. Further studies must show whether that can be extended to HF patients with preserved EF.