Rheumatic Heart Disease Group Research Articles

Vitamin (D) levels in children of families with a case of rheumatic fever or rheumatic heart disease

Background The most prevalent acquired heart illnesses in children are rheumatic fever (RF) and rheumatic heart disease (RHD). Differential regulation of innate immune cell subsets by vitamin D has been shown to effect cell maturation, metabolism, antigen presentation as well as cytokine and chemokine response and production. Aim The aim of this work was to evaluate vitamin D levels in children with acute RF and its relation to serum immunoglobulin levels. Patients and methods This cross-sectional study was conducted at Tanta University Hospital, Pediatric cardiology unit, outpatient clinic, and clinical pathology unit in two groups: group 1 which included 49 children who were subdivided into: group 1a: which included 10 RF or RHD patients and group 1b: included 39 children (brothers or sisters of rheumatic patients). Group 2 (control group): included 40 apparently healthy children of matched age and sex. All patients were subjected to full history taking, echocardiographic examination and laboratory investigations (Vitamin D3, erythrocyte sedimentation rate, antistreptolysin O titre, C-reactive protein (CRP), Calcium (Ca), phosphorus, immunoglobulins G (IgG), complement 3 (C3), and complement 4 (C4). Results There is a statistically significant decrease Ca, C4, and vit D3 levels in patient group compared with the control group. Vitamin D level was positively correlated with C4 levels. There is no statistically significant change was recorded regarding Ph, immunoglobulins G, or C3. Conclusion Children with RHD and children in families with RF or RHD are risky for vitamin D deficiency.

Glycyrrhizin improves cardiac function in rheumatic heart disease by regulating Cx43 through miRNA-223

Rheumatic heart disease (RHD) is a typical and relapsing autoimmune disease that damages heart valve. In this study, glycyrrhizin was used to intervene RHD mouse model to explore the role of glycyrrhizin in RHD and underlying mechanism. The RHD mouse model was successfully established and divided into 7 groups as follows: healthy group, RHD group, miR-223 antagonist group, miR-223 agonist group; glycyrrhizin group and glycyrrhizin+agonist group, and glycyrrhizin+miR-223 antagonist group. After treatment, cardiac function was evaluated by weighing the heart, echocardiography, and observing cardiomyocytes with Masson staining and hematoxylin-eosin staining (HE) staining. Real Time Quantitative (RT-qPCR) and Western blot determined miR-223 and Cx43 expressions and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) assessed proliferation rate after transfection. The cardiac function, as well as cardiomyocyte morphology of the glycyrrhizin group were significantly improved (P <0.05). Importantly, additional treatment with miR-223 antagonist further improved cardiac function, dramatically decreasing left ventricular end-diastolic dimension (LVEDD) and Left Ventricular End Systolic Diameter (LVESD). Besides, glycyrrhizin treatment decreased miR-223 expression while increasing Cx43 expression, compared with RHD group. Combination of miR-223 antagonist and glycyrrhizin obtained the highest level of Cx43. Anti-miR-223+pcDNA-Cx43 group had the lowest proliferation rate and highest apoptosis rate of mouse RHD cells. Glycyrrhizin inhibited miR-223 and increased Cx43 expression to strengthen cardiac function and restrict progression of RHD mice, which is an intervention target for RHD.

LINC00707 inhibits myocardial fibrosis and immune disorder in rheumatic heart disease by regulating miR-145-5p/S1PR1

ABSTRACT LINC00707 is a lncRNA that can regulate a variety of diseases. This study mainly investigated that the expression of LINC00707 in rheumatic heart disease (RHD) and LINC00707 regulates S1PR1 by targeting miR-145-5p to inhibit myocardial fibrosis and immune disorder in RHD. A rat model of RHD induced by inactivated group A β-hemolytic streptococcus (GSA) was established. Sixty female Lewis rats (8 weeks of age) were randomly divided into six groups, including control (Con), RHD, RHD+NC, RHD+LINC00707, RHD+miR-145-5p and RHD+LINC00707+miR-145-5p. The mRNA expression was detected by Quantitative Real-time polymerase chain reaction (qRT-PCR). Protein expression of S1PR1 was detected by western blot. The levels of myocardial damage markers (CK-MB, cTnl) and inflammatory immune markers (IL-6, IL-17 and IL-21) were measured by enzyme linked immunosorbent assay (ELISA). The Collagen III/I(COLIII/I) ratio, mRNA expression of COLIIIα1 and FSP1 of rat heart valve tissue in the RHD group was observably higher by comparison with the CON group. The expression of LINC00707 was observably lower in the RHD group. LINC00707 inhibited myocardial fibrosis and immune disorder in RHD. MiR-145-5p was the target gene of LINC00707 via Targetscan prediction. Luciferase reporter experiment confirmed that miR-145-5p was directly regulated by LINC00707. The expression of miR-145-5p in the RHD group was observably higher by comparison with the CON group and LINC00707 observably decreased the expression of miR-145-5p. miR-145-5p mimic reversed the inhibiting effect of LINC00707 on myocardial fibrosis and immune disorder. Furthermore, S1PR1 was confirmed to be downstream gene of miR-145-5p and low expressed in the RHD model. LINC00707 could inhibit myocardial fibrosis and immune disorder in RHD by regulating miR-145-5p/S1PR1.

Toward the development of a polarimetric tool to diagnose the fibrotic human ventricular myocardium.

.SignificanceOptical polarimetry is an emerging modality that effectively quantifies the bulk optical properties that correlate with the anisotropic structural properties of cardiac tissues. We demonstrate the application of a polarimetric tool for characterizing healthy and fibrotic human myocardial tissues efficiently with a high degree of accuracy.AimThe study was aimed to characterize the myocardial tissues from the left ventricle and right ventricle of control and diseased subjects. The diseased subjects were composed of two groups: with rheumatic heart disease (RHD) and with myxomatous valve (MV) disease.ApproachA portable, affordable, and accurate linear polarization-based diagnostic tool is developed to measure the degree of linear polarization (DOLP) of the myocardial tissues while working at a wavelength of 850 nm.ResultsThe sensitivity, specificity, and accuracy of the polarimetric tool in distinguishing the control group from the RHD group were found to be 73.33%, 76.92%, and 75%, respectively, and from the MV group were 91.6%, 62.5%, and 80%, respectively, which demonstrates the efficacy of the polarimetric tool to distinguish the healthy myocardial tissues from diseased tissues.ConclusionsWe have successfully developed a polarimetric tool that can aid cardiologists in characterizing the myocardial tissues in conjunction with endomyocardial biopsy. This work should be followed up with experiments on a large cohort of control and diseased subjects. We intend to create and develop a probe to quantify the DOLP of in vivo heart tissue during surgery.

Systemic cytokines, chemokines and growth factors reveal specific and shared immunological characteristics in infectious cardiomyopathies

Heart disease is a major cause of death worldwide. Chronic Chagas cardiomyopathy (CCC) caused by infection with Trypanosoma cruzi leading to high mortality in adults, and rheumatic heart disease (RHD), resulting from infection by Streptococcus pyogenes affecting mainly children and young adults, are amongst the deadliest heart diseases in low-middle income countries. Despite distinct etiology, the pathology associated with both diseases is a consequence of inflammation. Here we compare systemic immune profile in patients with these cardiopathies, to identify particular and common characteristics in these infectious heart diseases. We evaluated the expression of 27 soluble factors, employing single and multivariate analysis combined with machine-learning approaches. We observed that, while RHD and CCC display higher levels of circulating mediators than healthy individuals, CCC is associated with stronger immune activation as compared to RHD. Despite distinct etiologies, univariate analysis showed that expression of TNF, IL-17, IFN-gamma, IL-4, CCL4, CCL3, CXCL8, CCL11, CCL2, PDGF-BB were similar between CCC and RHD, consistent with their inflammatory nature. Network analysis revealed common inflammatory pathways between CCC and RHD, while highlighting the broader reach of the inflammatory response in CCC. The final multivariate model showed a 100% discrimination power for the combination of the cytokines IL-12p70, IL-1Ra, IL-4, and IL-7 between CCC and RHD groups. Thus, while clear immunological distinctions were identified between CCC and RHD, similarities indicate shared inflammatory pathways in these infectious heart diseases. These results contribute to understanding the pathogenesis of CCC and RHD and may impact the design of immune-based therapies for these and other inflammatory cardiopathies that may also share immunological characteristics.

Evaluating Community Engagement Strategies to Manage Stigma in Two African Genomics Studies Involving People Living with Schizophrenia or Rheumatic Heart Disease.

In global health research and genomics research specifically, community engagement has gained prominence in enhancing ethical conduct, particularly in managing the risk of stigmatization, but there is minimal scientific evidence on how to do this effectively. This article reports on community engagement evaluation strategies in two African genomics studies: the Stigma in African Genomics Research study and the Genomics of Schizophrenia in South African Xhosa People (SAX) study. Within the Stigma in African Genomics Research study, a self-report rating scale and open-ended questions were used to track participant responses to an experiential theatre workshop. The workshop focused on participant experiences of living with schizophrenia or rheumatic heart disease (RHD). While the schizophrenia group reported more alienation and less stigma resistance than the RHD group, both groups demonstrated increased stigma resistance over time, after participating in the workshops. Hearing from others living with and managing the same illness normalised participants' own experiences and encouraged them. Within the SAX study, a short rating scale and qualitative feedback methods were used to evaluate a Mental Health Literacy Day targeting mental health stigma. Information talks about (i) the symptoms of schizophrenia and treatment options and (ii) the illness experiences of a patient in recovery were rated as the most helpful on the day. Audience members reported that these talks challenged negative perceptions about severe mental illness. Three important learnings emerged from these evaluations: firstly, integration of evaluation strategies at the research study planning phase is likely to promote more effective community engagement. Secondly, a combination of quantitative and qualitative methods that draw on simple descriptive statistics and thematic analysis can provide nuanced perspectives about the value of community engagement. Thirdly, such evidence is necessary in establishing and promoting the science of community engagement in genomics research and health research more broadly.

A longitudinal study of antibody responses to selected host antigens in rheumatic fever and rheumatic heart disease.

Introduction. Group A streptococci can trigger autoimmune responses that lead to acute rheumatic fever (ARF) and rheumatic heart disease (RHD).Gap Statement. Some autoantibodies generated in ARF/RHD target antigens in the S2 subfragment region of cardiac myosin. However, little is known about the kinetics of these antibodies during the disease process.Aim. To determine the antibody responses over time in patients and healthy controls against host tissue proteins - cardiac myosin and peptides from its S2 subfragment, tropomyosin, laminin and keratin.Methodology. We used enzyme-linked immunosorbent assays (ELISA) to determine antibody responses in: (1) healthy controls; (2) patients with streptococcal pharyngitis; (3) patients with ARF with carditis and (4) patients with RHD on penicillin prophylaxis.Results. We observed significantly higher antibody responses against extracellular proteins - laminin and keratin in pharyngitis group, patients with ARF and patients with RHD when compared to healthy controls. The antibody responses against intracellular proteins - cardiac myosin and tropomyosin were elevated only in the group of patients with ARF with active carditis. While the reactivity to S2 peptides S2-1-3, 8-11, 14, 16-18, 21-22 and 32 was higher in patients with ARF, the reactivity in the RHD group was high only against S2-1, 9, 11, 12 when compared to healthy controls. The reactivity against S2 peptides reduced as the disease condition stabilized in the ARF group whereas the reactivity remained unaltered in the RHD group. By contrast antibodies against laminin and keratin persisted in patients with RHD.Conclusion. Our findings of antibody responses against host proteins support the multistep hypothesis in the development of rheumatic carditis. The differential kinetics of serum antibody responses against S2 peptides may have potential use as markers of ongoing cardiac damage that can be used to monitor patients with ARF/RHD.

An evidence-based scoring system to diagnose acute rheumatic fever with carditis in children

BackgoundAcute rheumatic fever (ARF) with carditis and chronic rheumatic heart disease (RHD) may be difficult to differentiate and may lead to missed diagnosis of carditis. We aimed to determine differences between these groups and to develop a new scoring system for this purpose. MethodsChildren (N = 514; mean age 11.6 ± 2.8, range 5–18 years; 65% males) enrolled in a RHD registry at a tertiary care centre were studied. Clinical, laboratory and echocardiographic features of acute rheumatic carditis group (N = 126) were compared with chronic RHD group (N = 388). We performed multiple regression analysis and then developed a new scoring system using independent predictors. Accuracy of this scoring system was assessed using receiver operating characteristic (ROC) curve analysis. ResultsPatients with ARF and carditis were younger, more commonly had history of fever, arthritis/arthralgias and had worse NYHA class. On echocardiography, severity of mitral regurgitation, presence of mitral leaflet nodules, mitral valve prolapse and pericardial effusion were more common in ARF group. On multiple regression analysis, following features were found to be independently predictive of ARF with carditis: age -negative association, NYHA class, severity of mitral regurgitation, mitral leaflet nodules, erythrocyte sedimentation rate and antistreptolysin titer. Based on these 6 variables, a new scoring system (0−13) was developed. A score of 5 or more was found to be best threshold for diagnosis of carditis (ROC AUC 0.87, sensitivity 76%, specificity 79%). ConclusionA new scoring system based on independent statistical associations appears promising for differentiating ARF with carditis from chronic RHD.

Strain patterns in primary mitral regurgitation due to rheumatic heart disease and mitral valve prolapse

ObjectiveLeft atrial (LA) and left ventricular (LV) remodelling are the adaptive changes that occur in primary mitral regurgitation (MR) and are related to its clinical outcomes. Despite the pathophysiological differences in MR in rheumatic heart disease (RHD) and mitral valve prolapse (MVP), whether the pattern of LV and LA remodelling is different between the two conditions remains unknown. Hence, we compared the LA and LV strain pattern in MR due to RHD, the predominant etiology in developing countries topatients with MVP and age and sex-matched controls. MethodsA total of 50 patients of severe MR which included 30 MVP MR and 20 RHD MR were assessed by strain imaging by speckle tracking echocardiography (STE) and were compared with age and sex-matched controls. 2D STE was used for LA and 3D STE was used for LV strain analysis. LA and LV strain parameters were compared between MVP MR and RHD MR groups. Results30 patients with MVP and 20 with RHD were studied. 60% (n = 30) were symptomatic. Mean GLS was −17.2 ± 4.4% compared to −20 ± 3.2% among controls and mean LA strain was 17.35 ± 10.3% compared to 51.34 ± 11.5% among controls which were significantly lower (both p < 0.01). No significant difference in LA strain and GLS was found between MVP and RHD subgroups (LA strain 20.45 ± 11.9% and 14.63 ± 8.85%; p = 0.08; GLS - 18.25 ± 4.3% and-16.2 ± 4.6%; p = 0.12). PALS in the RHD group was lower compared to MVP(p = 0.08) which showed a trend towards significance. LV strain parameters showed no significant difference among the MVP and RHD groups. ConclusionLA and LV strain parameters showed no significant difference in MR due to either RHD or MVP. There was a trend towards lower LA strain in RHD which needs validation with large multicentric studies. The current strain parameters from MVP with the prognostic value may be applied to MR of RHD etiology, pending confirmation of our results by other groups.

Activation of activin/Smad2 and 3 signaling pathway and the&amp;nbsp;potential involvement of endothelial‑mesenchymal transition in the valvular damage due to rheumatic heart disease

Rheumatic heart disease (RHD) is an autoimmune disease caused by rheumatic fever following group A hemolytic streptococcal infection and primarily affects the mitral valve. RHD is currently a major global health problem. However, the exact pathological mechanisms associated with RHD-induced cardiac valve damage remain to be elucidated. The endothelial-mesenchymal transition (EndMT) serves a key role in a number of diseases with an important role in cardiac fibrosis and the activin/Smad2 and 3 signaling pathway is involved in regulating the EndMT. Nevertheless, there are no studies to date, to the best of the authors' knowledge, investigating the association between RHD and EndMT. Thus, the aim of the current study was to investigate the potential role of EndMT in cardiac valve damage and assess whether activin/Smad2 and 3 signaling was activated during RHD-induced valvular injury in a rat model of RHD induced by inactivated Group A streptococci and complete Freund's adjuvant. Inflammation and fibrosis were assessed by hematoxylin and eosin and Sirius red staining. Serum cytokine and rheumatoid factor levels were measured using ELISA kits. Expression levels of activin/Smad2 and 3 signaling pathway-related factors [activin A, Smad2, Smad3, phosphorylated (p-)Smad2 and p-Smad3], EndMT-related factors [lymphoid enhancer factor-1 (LEF-1), Snail1, TWIST, zinc finger E-box-binding homeobox (ZEB)1, ZEB2, α smooth muscle actin (α-SMA) and type I collagen α 1 (COL1A1)], apoptosis-related markers (BAX and cleaved caspase-3) and valvular inflammation markers (NF-κB and p-NF-κB) were detected using reverse transcription-quantitative PCR and western blot analyses. Compared with the control group, the degree of valvular inflammation and fibrosis, serum levels of IL-6, IL-17, TNF-α and expression of apoptosis-related markers (BAX and cleaved caspase-3) and valvular inflammation marker (p-NF-κB), activin/Smad2 and 3 signaling pathway-related factors (activin A, p-Smad2 and p-Smad3), EndMT-related factors (LEF-1, Snail1, TWIST, ZEB 1, ZEB2, α-SMA and COL1A1) were significantly increased in the RHD group. These results suggested that the activin/Smad2 and 3 signaling pathway was activated during the development of valvular damage caused by RHD and that the EndMT is involved in RHD-induced cardiac valve damage.

How is juvenile rheumatic heart disease different: baseline results from a prospective north Indian registry

Abstract Introduction Juvenile rheumatic heart disease (RHD) refers to RHD in patients &amp;lt;20 years of age. There are no contemporary data highlighting the differences between juvenile and older RHD patients. Purpose We aim to report the age related differences in the pattern, and consequencies of valvular dysfunction in patients of RHD. Methods The 2475 consecutive patients of RHD diagnosed using clinical and echocardiographic criteria were registered prospectively from 2011 till December 2019. Patients were divided into 3 groups according to their age: Group 1 (Juvenile RHD), Group 2 (21–50 years), and Group 2 (&amp;gt;51 years).The data concerning the socio-demographic and clinical profile were recorded systematically, and the nature and severity of valvular dysfunction was assessed by echocardiography. The data were analyzed using the Epi-InfoTM Software. Results Out of 2475 RHD patients, Juvenile RHD comprised of 211 (8.5%) patients. Group 2 and 3 comprised of 1691 (68.3%) and 573 (23.2%) patients respectively. Overall, 1767 (71.4%) patients were females, however this female predilection was less pronounced in juvenile RHD (55.5% females vs 44.5% males) as compared to older groups. Past history of acute rheumatic fever was more commonly recorded in Juvenile RHD group (37.9% vs 18.8% in group 2 and 10% in group 3, p=0.0001). At the time of registration, the presence of advanced heart failure symptoms (dyspnea class III and IV) (11.4% group 1 vs 13.9% group 2 vs 20.6% group 3, p&amp;lt;0.0001), right heart failure symptoms (0.9% group 1 vs 2.5% group 2 vs 7.3% group 3, p&amp;lt;0.01), thromboembolic events (0% group 1 vs 4.1% group 2 vs 3.3% group 3, p&amp;lt;0.01), atrial fibrillation (2.8% group 1 vs 24.5% group 2 vs 45.9% group 3, p&amp;lt;0.0001), and pulmonary hypertension (27.1% group 1 vs 40.3% group 2 vs 51.9% group 3, p&amp;lt;0.01), were all more commonly recorded in non-juvenile older RHD groups. Multivalvular involvement was also less common in juvenile RHD (34.6% vs 42.4% and 44.5%, p=0.04). Mitral regurgitation was the most common lesion in Juvenile RHD followed by aortic regurgitation (68.7% and 40.2% respectively). Stenotic lesions (both mitral and aortic) were present more commonly in older age groups. Conclusion RHD is predominantly a disease of females, however the predilection is less common in juvenile patients. Juvenile RHD predominantly affects the mitral valve and mainly leads to regurgitant lesions. As the age advances, the complications of RHD, mainly heart failure symptoms, thromboembolic events, pulmonary hypertension, and atrial fibrillation, become more common. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Self sponsored registry

Role of Carboxy Terminal Propeptide of Type I and Type III Procollagen (PICP and PIIICP) Toward the Severity Degree of Mitral Valve Regurgitation in Children’s Rheumatic Heart Disease

BACKGROUND: Rheumatic heart disease (RHD) is recognized as a heart disease that occurs as a result of sequelae in acute rheumatic fever (ARF), characterized by the occurrence of defects in the heart valves. The most common manifestation of childhood RHD is mitral regurgitation (MR). The role of inflammation and oxidative stress in RHD also involves several components consisting of carboxy-terminal pro-peptide of Type I procollagen (PICP) and carboxy-terminal pro-peptide of Type III procollagen (PIIICP).&#x0D; AIM: The aim of this study was to know whether PICP and PIIICP can be used to measure the severity level of mitral valve regurgitation.&#x0D; METHODS: This research is considered as descriptive-analytic research, and using cross-sectional analysis. Forty RHD patients underwent echocardiographic examinations to measure Wilkin and effective regurgitant orifice area scores. Patients were classified into ARF without valve abnormalities, mild, moderate, and severe MR. PICP and PIIICP were with ARF through venous blood and ELISA was examined. Data were analyzed by employing SPSS 22 with p = 0.05). Wilkins scores and PICP levels have a regression coefficient of 0.296 with a p-value of 0.032.&#x0D; RESULTS: There was a significant difference in PICP level among the studied sample groups with a p = 0.012, (p &lt; 0.05), with insignificant difference in PIIICP level among sample groups with a p = 0.083, greater than α = 0.05 (p &gt; 0.05). Wilkins scores and PICP level have a regression coefficient of 0.296 with a p = 0.032 (p &lt; 0.05), while PIIICP level has a regression coefficient of 0.093 with a p = 0.568 (p &gt; 0.05).&#x0D; CONCLUSION: There is no significant increase indicated on PIIICP level, but PICP level indicates a significant increase in RHD group with severe mitral valve abnormalities. PICP can be used to measure the severity level of mitral valve regurgitation.&#x0D;

Clinical and Biochemical Assessments of Circulating B-Type Natriuretic Peptide as a Useful Marker in Pediatric Cardiac Patients

Background Although the left ventricle is the major site of BNP secretion in response to cardiac pressure or volume overload, the myocytes of both atria and ventricles secrete B- type natriuretic peptide (BNP). This study aimed to assess and compare the plasma levels of BNP in common pediatric cardiac diseases to clarify its pathophysiological role and evaluate its possible diagnostic and prognostic utility in pediatric patients with congenital heart disease (CHD), and heart failure (HF). Materials and Methods: The study is a prospective, case-control research including 131 pediatric patients selected from Pediatric Department of South Valley University Hospitals in Qena, Egypt, with a variety of cardiac diseases and 70 healthy controls. The patients were categorized into 4 groups: 61 newly diagnosed pediatric patients with CHD, 30 patients with HF, 20 pediatric patients with cardiomyopathy (CM), and 20 children with rheumatic heart disease (RHD). Clinical and echocardiographic assessments for the pediatric patients were performed. Bioassays of plasma BNP using commercially available ELISA assay kits were performed to the study the participants. Results: The median plasma BNP levels were significantly higher in the CHD, HF and CM groups than the RHD and control groups, with p Conclusion The validity of plasma BNP in diagnosing HF was significantly superior to its utility in predicting CHD among pediatric patients.

Circulating follicular T helper cells and humoral reactivity in rheumatic heart disease

AimsThis study aimed to profile circulating T follicular helper cells (cTfh) and their effect on B cells in rheumatic heart disease (RHD). Materials and methodsParticipants were divided into healthy control (HC, n = 30) and RHD (n = 30) groups. Percentages of cTfh subpopulations, based on CD4, CXCR5, CXCR3, CCR6, Foxp3, Ki67, and PD-1 cell markers, and of CD19+ B cell subgroups were measured by flow cytometry and compared between the groups. Also, IL-21 concentration in plasma and mitral valve were quantitated by cytometric bead array, immunofluorescence, and western blotting. Key findingsThe PD-1+ cTfh, B cells (naive B cells, plasmablasts, and plasma B cells) proportion and cTfh17/cTfh ratios in RHD group were significantly increased, compared to HC (p < 0.01 in all cases), while different types of memory B cells were diminished (p < 0.001). In RHD patients, percentages of PD-1+ cTfh and switched memory B cells were negatively correlated (r = −0.565, p = 0.009); meanwhile, percentages of plasmablasts and PD-1+ cTfh cells were positively correlated (r = 0.594, p = 0.005). Additionally, IL-21 levels in plasma and mitral valve of RHD group were higher than those in HC. Also, IL-21 levels correlated with PD-1+ cTfh(r = 0.557, p = 0.010), cTfh17 (r = 0.567, p = 0.009), and plasmablast (r = −0.5957, p = 0.005) cell proportions, and (cTh2 + cTh17)/cTfh1 ratio (r = −0.547, p = 0.013). SignificanceThe activation of PD-1+ cTfh and cTfh17 subtype was highly correlated with plasmablast maturation and IL-21 production in rheumatic heart disease. Thus indicating the prominent role of cTfh and humoral reactivity in the immune pathogenesis of RHD.

The Polymorphism at the microRNA-155 Binding Site in the AGTR1 Gene is not Significantly Associated with Rheumatic Heart Disease in Saudi Arabia Population

Rheumatic Heart Disease (RHD) remains a major cause of cardiovascular diseases and the most devastating effects are shown on children and young adults. RHD is caused due to the interaction between microbial, environmental, immunologic, and genetic factors. The Renin- Angiotensin Aldosterone System (RAAS) has been strongly implicated as the susceptibility pathway in the pathogenesis of the cardiovascular disease. The present study investigated the modulating effect of Angiotensin II type 1 receptor (AGTR1) 1166A>C polymorphism on the RHD and its clinical features in Saudi Arabia. AGTR1 1166A>C polymorphism was genotyped in 96 echocardiographically confirmed RHD patients and 142 ethnically matched controls by the TaqMan allelic discrimination method. Genotype distribution of the AGTR1 1166A>C polymorphism was not significantly different between RHD and control groups. Furthermore, AGTR1 1166A>C genotypes are not associated with the clinical features of RHD. These data support that there was no evidence for an association between AGTR1 1166A>C polymorphism and RHD in Saudi Arabia. To the best of our knowledge, this is the first study that has investigated the possible association between AGTR1 1166A>C polymorphism and susceptibility to RHD and its clinical features. Even though the AGTR1 gene, 1166A>C (rs5186), was reported to be associated with hypertension, left ventricular hypertrophy and coronary heart disease. The present study did not find any association between AGTR1 1166A>C polymorphism and RHD in Saudi Arabia. Further studies are needed to confirm our findings.

P909 Diagnostic evaluation of rheumatic heart disease in aborigonal population

Abstract Background Among Indigenous Australians, rates of Acute Rheumatic Fever (ARF) continue to be among the highest in the world. Diagnosis remains a clinical decision based on identification of major and minor manifestations of the illness. Treatment involves lengthy prophylaxis and should continue for a minimum of 10 years. ARF can cause permanent damage to the heart known as rheumatic heart disease (RHD). We therefore utilised echocardiography as a diagnostic tool incorporating Tissue Quantification Backscatter expressed in decibels (dB) and global LV work efficiency estimated from left ventricle (LV) pressure-strain loops to identify rheumatic changes of the Mitral Valve and help improve early diagnosis of RHD. Method Data from patients with suspected RHD (n = 14), and age matched controls (n = 10) underwent Mitral Valve Backscatter Analysis (MVBS). MVBS was expressed as a ratio % (MVBS ratio %) by dividing the average MVBS and the average blood pool value expressed in decibels (dB). Furthermore LV function was utilised via 2D longitudinal strain and indices of myocardial work were derived. Result MVBS ratio % was significantly higher in the control group as compared to the RHD group (p = 0.001) (fig1). Of the RHD group echocardiography parameters showed there were no significant mitral valve stenosis or regurgitation. Correlates of LV function included: Global work Index (GWI), Global longitudinal Strain (GLS) and Global work efficiency (GWE). Of the above correlates the control group showed Backscatter vs GLS (r= -0.89, p = 0.001), the RHD group: Backscatter vs GLS (r = 0.52. p = 0.12). Within the RHD group the ratio vs GWE (r= 0.57, p = 0.09) these results showed a trend to significance. Conclusions Currently diagnosis of RHD remains a clinical decision based on the identification of major and minor manifestations. In addition treatment involves prophylaxis injections for a minimum of ten years. Of this group there were no significant echocardiography changes, rather clinical manifestation to derive RHD. This study shows that calibrated MVBS ratio % and determinants of myocardial work may be a promising quantitative tool to detect early manifestation of RHD potentially aiding an early treatment plan and thus reducing the clinical burden of monthly penicillin injections for a ten year period. Abstract P909 Figure. RHD and Myocardial correlates

Long-term outcomes of radiofrequency catheter ablation for atrial fibrillation in rheumatic heart disease patients with mild mitral stenosis.

To assess efficacy of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) in rheumatic heart disease (RHD) patients with mild mitral stenosis (MS). This retrospective cohort study included 62 consecutive RHD patients with mild MS and AF and 124 AF patients without RHD with matched age, gender, AF types as control. Procedure endpoints were defined as circumferential pulmonary vein ablation (CPVA) for paroxysmal AF, CPVA plus bidirectional block of lines, and disappearance of complex fractionated atrial electrograms for non-paroxysmal patients in both groups. Cumulative success rate during the total follow-up (RHD, 23-140months; control, 24-140months) was lower in RHD group than control (32.3 vs. 56.5%, log-rank P = 0.006). In RHD patients, the success rate was higher in paroxysmal AF patients than non-paroxysmal AF patients during the mid-term follow-up (55.0 vs. 26.2%, log-rank P = 0.041), and was similar between the two AF types during the total follow-up (45.0 vs. 26.2%, log-rank P = 0.130). Patients without mitral regurgitation (MR) or with mild MR had a higher success rate than patients with moderate MR during the total follow-up in both groups (45.0 vs. 9.1%, log-rank P = 0.014 in RHD group; 64.5 vs. 43.8%, log-rank P = 0.001 in control group). The long-term outcome of RFCA for AF in RHD patients with mild MS was mediocre and worse than that for AF patients without RHD. The severity of MR was associated with RFCA outcome in both groups. In RHD patients with mild MS, a better prognosis of paroxysmal AF than non-paroxysmal AF was observed initially but turned similar over time.

Heart transplantation outcomes for rheumatic heart disease: Analysis of international registry data.

Rheumatic heart disease (RHD), an autoimmune sequela of Group A streptococcal infection, is a chronic valvular disease affecting 32 million people worldwide, predominantly in developing nations. As the predisposition to autoimmune sequela still remains post transplantation, our primary objective was to assess if there were differences in mortality and rejection rates. Using the International Society for Heart and Lung Transplantation (ISHLT) adult heart transplant registry, we identified 42 RHD patients who had undergone heart transplantation between 1988 and 2014. We matched the 42 RHD recipients by transplant year, age, and gender to 420 dilated cardiomyopathy (DCM) recipients. One-year mortality in the RHD group was 17.95% vs. 7.92% in the DCM group (P=0.07). Survival was significantly reduced in the RHD group vs. the DCM group via Kaplan Meier curves (P=0.04). In a multivariate model, RHD status (OR 3.19, 95% CI 1.15-8.83, P=0.025) and serum creatinine (OR 1.41, 95% CI 1.09-1.82, P=0.009) were associated with an increased odds of one-year mortality (P=0.0013). At one year post transplantation, RHD recipients had a significantly lower survival than DCM recipients. RHD status was also an independent predictor of mortality at 1year post transplantation.

Prevalence and patterns of coronary artery disease in patients undergoing cardiac surgery for rheumatic and non- rheumatic valvular heart disease in a tertiary care center of Nepal

Background and Aims: Coronary artery disease (CAD) constitute a major cause of cardiovascular morbidity and mortality worldwide with an enormous burden on healthcare resources. Prevalence and pattern of CAD in patients of rheumatic and non-rhemuatic valvular heart diseases varies widely with limited data on optimal strategies for diagnosis and treatment.Methods: This study includes 97 patients with rheumatic and non-rheumatic valvular heart disease who underwent coronary angiogram (CAG) before cardiac surgery. Patients were divided into two groups based on rheumatic heart disease (RHD) &amp; non-rheumatic disease (Non-RHD) and correlate the patterns of CAD.Results: Out of 97 patients, 22 (22.6%) patients were found to have significant CAD. In patients with non-rheumatic origin CAD was common (15 patients, 68.1%) as compared to rheumatic origin (7 patients, 31. 8%). In rheumatic origin, the prevalence was 7(12.2%) out of 57 patients while in non-rheumatic origin, was 15(37.5%) out of 40 patients. In RHD group, all patients with CAD were found to have single vessel diease (SVD) while, in non-RHD group, 11 patients (73.3%) had SVD, 3 patients (16.7%) had double vessel disease (DVD) and one patient (5.6%) had triple vessel disease (TVD).Conclusions: Prevalence of CAD is higher in patients with non-RHD in comparison to those with RHD. We also found SVD to be the most common pattern of CAD in both rheumatic and non-rheumatic valvular heart disease.

Presence of increased inflammatory infiltrates accompanied by activated dendritic cells in the left atrium in rheumatic heart disease.

AimsLeft atrial (LA) structural remodelling develops in rheumatic heart disease (RHD) according to the disease severity of the mitral valve and the presence of atrial fibrillation. Sustained active inflammation has been previously reported in the LA of patients with RHD, suggesting a direct role of cell-mediated immunity in the pathogenesis of LA remodelling. Dendritic cells (DCs) have a major antigen-presenting role, and are known as crucial modulators of innate and adaptive immunity. We investigated whether DCs are involved in the pathogenesis of LA remodelling in RHD.Methods and resultsImmunohistochemical analyses were performed using antibodies to CD11c, CD209 and CD80 as markers of myeloid DCs, migratory-active DCs, mature DCs and infiltrated inflammatory cells including T lymphocytes (CD3) and M1 (CD68; pro-inflammatory profile) and M2 (CD163; pro-resolution profile) macrophages. Furthermore, tenascin-C, an extracellular matrix (ECM) protein that appears during ECM remodelling and inflammatory response, was examined. Infiltrated myeloid DCs, migratory-active DCs, mature DCs and other inflammatory infiltrates including T lymphocytes and M1 and M2 macrophages, were significantly higher in the RHD group than the non-RHD group. The positive area fraction for tenascin-C was significantly higher in the RHD group than in the non-RHD group.ConclusionOur histological findings suggest that inflammation may persist long after a bout of rheumatic fever, ultimately leading to ECM remodelling. We identified and quantitatively assessed several subsets of DCs and other immunocompetent cells, and our results indicated that activation of DCs has some role in persistence of LA inflammation in patients with chronic RHD.