Chronic Rheumatic Heart Disease Patients Research Articles

INDEX ASSESSMENT OF PERIODONTAL TISSUES AND DETERMINATION OF TREATMENT NEEDS IN PATIENTS WITH CHRONIC RHEUMATIC HEART DISEASE

This study addresses the pressing scientific and practical issue in modern dentistry: enhancing dental care effectiveness for patients with chronic rheumatic heart disease. The purpose of this research is to comprehensively assess the condition of tooth-supporting tissues and quantify inflammatory phenomena in periodontal tissues among patients with chronic rheumatic heart disease, as well as to determine the necessary extent of periodontal care based on periodontal indices. Participants and methods. The periodontal tissues of 719 patients with chronic rheumatic heart disease from the Rheumatology Department of Lviv Regional Clinical Hospital, along with 290 clinically healthy individuals in the comparison group, were examined. To evaluate the clinical course of dystrophic-inflammatory periodontal diseases in patients with chronic rheumatic heart disease, we examined 267 individuals in the main group who had generalized periodontitis, categorized as follows: 42 patients with initial stage (I degree), 115 with moderate (II degree), and 110 with severe (III degree) periodontitis. The comparison group comprised 70 patients diagnosed with generalized periodontitis, among them, 21 had initial-stage disease, 29 had moderate-stage disease, and 20 had severe-stage disease. During the analysis, the oral hygiene was assessed by applying hygienic indices by J.C. Green and J.R. Vermillion (OHI-S, 1964) and Fedorov-Volodkina. The Muhlemann and Son index was used to objectively measure gingival papillary bleeding (RVI); the papillary-marginal-alveolar index (PMA) in the Parma modification, in combination with the Schiller-Pysarev test (1989), was employed to evaluate gingival inflammation. The periodontal index (PI) by A.L. Russel (1956) was used to assess the state of periodontal tissues, and pathological changes were recorded using the periodontal screening PSR test. Results were scored, and based on established criteria and scores, the need for treatment and its extent were determined. Results and discussion. According to the results of dental examinations in patients with chronic rheumatic heart disease, a high prevalence of periodontal diseases was found, reaching 92.49%. This was 13.18% higher compared to the prevalence in the control group. Dystrophic-inflammatory conditions with advanced severity levels were predominant, as evidenced by the index indicators. In chronic rheumatic heart disease patients, the average periodontal index was 6.11±0.10, compared to 4.14±0.19 in clinically healthy individuals (p < 0.05). Moreover, a higher lesion of periodontal tissues was observed in younger age groups. As the duration of rheumatic disease increased, the frequency of detecting generalized periodontitis also increased, with this condition being diagnosed in all subjects with a 10-year history of rheumatic disease. Conclusion. The Analysis of the research data on the condition of periodontal tissues, along with objective index assessments, reveals the following: periodontal diseases are more prevalent in individuals with chronic rheumatic heart disease, particularly affecting younger age groups. The severity and progression of these diseases are influenced by the course of the underlying condition. This underscores the presence of pathogenetic conditions that contribute to the rapid progression of the dystrophic-inflammatory process in periodontal tissues. It also emphasizes the importance of providing specialized periodontal care to patients with chronic rheumatic heart disease, with the level of care directly linked to the course and duration of the systemic disease.

Tenascin-C: as a diagnostic biomarker for rheumatic heart disease

BackgroundRheumatic fever is a long-term inflammatory disease that can happen if group A beta-hemolytic streptococci bacteria are not treated well enough. Rheumatic fever is recognized globally as the leading cause of heart disease in the pediatric population. This disease destroys the heart muscle, progressively deteriorating its structure and impairing the function of its valves over time.AimThe aim of this study is to determine the role of serum tenascin-C in the diagnosis of acute rheumatic fever and chronic rheumatic heart disease.MethodsThis case–control study involved a group of 60 Egyptian children. Among them, 20 were diagnosed with acute rheumatic fever, identified using the updated Jones criteria from 2015. Another 20 children, who were suffering from chronic rheumatic heart disease, were also act as a part of the study. The remaining 20 participants, healthy children carefully matched in age and sex, served as the control group.ResultsSerum tenascin-C level was significantly increased in acute rheumatic fever (ARF) and highly significantly increased in chronic rheumatic heart disease (CRHD) groups when compared with control group (P = 0.04, 0.01), respectively. There were highly significant difference between and within the studied groups regarding the mean of serum tenascin-C. Serum tenascin-C mean of ARF, CRHD, and control was 4.82 ± 18.7, 5.46 ± 1.6, and 3.78 ± 2.4, respectively, P = 0.02. Level of serum tenascin-C was lower in cases with severe mitral valve insufficiency. No significant link was found between the level of serum tenascin-C and C-reactive protein (CRP), ESR, and ASO titer, with a P-value greater than 0.5. ROC curve for serum tenascin-C in ARF patients was area under the curve = 0.682 (P = 0.05) with optimal serum tenascin-C cut-off point (> 3.76 ng/ml); ROC curve for serum tenascin-C in CRHD patients was AUC = 0.73 (P = 0.01) with cut-off point level (73.76 ng/ml).ConclusionPatients with ARF and CRHD have increased level of serum tenascin-C. Serum tenancin-C is superior in the diagnosis of ARF in comparison to CRP, ESR, and ASOT. Tenascin-C level can be used as a diagnostic marker for ARF and CRHD.

Left atrial strain predicts improvement in left atrial functions of severe rheumatic mitral stenoses undergoing successful percutaneous transmitral commissurotomy.

Chronic rheumatic heart disease (RHD) is prevalent in India. The mitral valve in isolation or combination with the aortic or tricuspid valve is involved in 31.6% and 52.8% of chronic RHD patients, respectively. The left atrium (LA) functions as a reservoir during the cardiac cycle. Therefore, the LA enlargement leads to longitudinal lengthening, measured as a positive strain, permitting the measurement of the longitudinal strain of LA. This study aimed to assess the LA functions using peak atrial longitudinal strain (PALS) in patients with severe rheumatic mitral stenoses (MS) in sinus rhythm who underwent successful percutaneous transvenous mitral commissurotomy (PTMC). We recruited 56 patients with severe rheumatic MS for the study, of which 06 PTMC procedures were considered unsuccessful. So, 50 patients of chronic severe rheumatic MS in sinus rhythm undergoing PTMC were enrolled in a tertiary care centre of the Armed Forces from August 2017 to May 2019. Patients included in the study were not consecutive, and patients with atrial fibrillation (AF) were excluded. PALS improved post-PTMC (P<.001) in this study, effectively concluding that PALS is impaired in patients with severe symptomatic MS and is acutely enhanced after treatment. PALS is a good indicator of LA function and may predict the success of PTMC on the rheumatic mitral valve.

Plausible Role of NLRP3 Inflammasome and Associated Cytokines in Pathogenesis of Rheumatic Heart Disease.

Rheumatic heart disease (RHD) is a post-streptococcal sequela caused by Streptococcus pyogenes. The global burden of disease is high among people with low socio-economic status, with significant cases emerging every year despite global eradication efforts. The current treatment includes antibiotic therapies to target strep throat and rheumatic fever and valve replacement strategies as a corrective measure for chronic RHD patients. Valvular damage and valve calcification are considered to be the end-stage processes of the disease resulting from impairment of the endothelial arrangement due to immune infiltration. This immune infiltration is mediated by a cascade of events involving NLRP3 inflammasome activation. NLRP3 inflammasome is activated by wide range of stimuli including bacterial cell wall components like M proteins and leukocidal toxins like nicotinamide dehydrogenase (NADase) and streptolysin O (SLO) and these play a major role in sustaining the virulence of Streptococcus pyogenes and progression of RHD. In this review, we are discussing NLRP3 inflammasome and its plausible role in the pathogenesis of RHD by exploiting the host-pathogen interaction mainly focusing on the NLRP3 inflammasome-mediated cytokines IL-1β and IL-18. Different therapeutic approaches involving NLRP3 inflammasome inactivation, caspase-1 inhibition, and blockade of IL-1β and IL-18 are discussed in this review and may be promising for treating RHD patients.

Influence of VKORC1 and CYP2C9 Polymorphisms on Daily Acenocoumarol Dose Requirement in South Indian Patients With Mechanical Heart Valves.

Chronic rheumatic heart disease (RHD) patients who undergo valve replacement with mechanical valves require lifelong anticoagulation. Acenocoumarol, a vitamin K antagonist has a narrow therapeutic range and wide inter-individual variability. Our aim was to investigate the influence of polymorphisms of VKORC1 and CYP2C9 genes on the mean daily dose requirement of acenocoumarol. 205 chronic RHD patients, with mechanical heart valves and on acenocoumarol therapy, were recruited. Genotyping for VKORC1 (-1639G>A and 1173C>T) and CYP2C9 (*2 & *3 alleles) polymorphisms was done by PCR-RFLP. There was complete linkage disequilibrium between VKORC1 polymorphisms (r2 = 0.98, D' = 1.0, LOD = 74.02). VKORC1 genotype distribution for GG/CC, GA/CT, and AA/TT were 57.6%, 36.1%, and 6.3%, respectively. CYP2C9 genotype distribution for *1/*1, *1/*3, *1/*2, *2/*2, and *2/*3 were 78.5%, 14.1%, 6.3%, 0.5%, and 0.5%, respectively. Patients with a wild type of both VKORC1 (-1639GG and 1173CC) and CYP2C9 gene variants required higher acenocoumarol dose compared to those with mutant genotype ( P = 0.023 and P = 0.008 respectively). On combined genotype analysis, patients having a combination of wild type of VKORC1 with wild type of CYP2C9 (44.4%) required higher daily dose compared to patients bearing heterozygous VKORC1 (-1639GA & 1173CT) with wild type of CYP2C9 (30.2%, P = 0.008). Presence of a mutant allele of VKORC1 (-1639A & 1173T) and CYP2C9 genes increased the odds of requiring a lower mean dosage of acenocoumarol. Studying the combination of genotypes in RHD patients could predict acenocoumarol dose requirement more accurately.

CXCL9/Mig Mediates T cells Recruitment to Valvular Tissue Lesions of Chronic Rheumatic Heart Disease Patients

Rheumatic fever (RF) is an autoimmune disease triggered by Streptococcus pyogenes infection frequently observed in infants from developing countries. Rheumatic heart disease (RHD), the major sequel of RF, leads to chronic inflammation of the myocardium and valvular tissue. T cells are the main population infiltrating cardiac lesions; however, the chemokines that orchestrate their recruitment are not clearly defined. Here, we investigated the expression of chemokines and chemokine receptors in cardiac tissue biopsies obtained from chronic RHD patients. Our results showed that CCL3/MIP1α gene expression was upregulated in myocardium while CCL1/I-309 and CXCL9/Mig were highly expressed in valvular tissue. Auto-reactive T cells that infiltrate valvular lesions presented a memory phenotype (CD4+CD45RO+) and migrate mainly toward CXCL9/Mig gradient. Collectively, our results show that a diverse milieu of chemokines is expressed in myocardium and valvular tissue lesions and emphasize the role of CXCL9/Mig in mediating T cell recruitment to the site of inflammation in the heart.

Effect of autoimmune diseases on risk and survival in female cancers

ObjectivesPatients with autoimmune (AI) diseases are diagnosed with increased frequencies of some cancers, which may depend on the underlying dysregulation of the immune system or treatment. Data on female cancers are limited. MethodsWe analyzed systematically risk and survival of female cancers of the breast, uterus, ovary and other genital organs in close to 200,000 patients diagnosed with any of 33 different AI diseases. Standardized incidence ratios (SIRs) for risk and hazard ratios (HRs) for survival were calculated for subsequent incident cancers or cancer deaths up to year 2008. ResultsFor all breast cancer after any AI diseases, the SIR was 0.94; SIRs were modestly increased after two AI diseases and decreased after nine AI diseases, including Sjogren syndrome (0.46). For cervical cancer, the risk was increased after discoid lupus erythematosus (3.34) and systemic sclerosis (2.43). The HR was 2.12 in chronic rheumatic heart disease patients. The overall SIR for endometrial cancer was 0.85, with low SIR in ankylosing spondylitis (0.37); the HR was 4.05 for Sjogren syndrome. The SIR for ovarian cancer was increased for polymyositis/dermatomyositis (3.26) while the HR was increased for multiple sclerosis (2.43). The overall SIR for other genital cancers was increased to 1.54 and a very high risk of 35.88 was observed in localized scleroderma. ConclusionsBreast, endometrial and ovarian cancers were decreased after all AI diseases and most significant changes after individual AI diseases were towards lower risks. Probably treatment related factors explain the findings. For cervical and other genital cancers all significant changes were increased risks.

PDIA3, HSPA5 and vimentin, proteins identified by 2-DE in the valvular tissue, are the target antigens of peripheral and heart infiltrating T cells from chronic rheumatic heart disease patients

Rheumatic fever (RF) is a post-infectious autoimmune disease due to sequel of group A streptococcus (GAS) pharyngitis. Rheumatic heart disease (RHD), the major manifestation of RF, is characterized by inflammation of heart valves and myocardium. Molecular mimicry between GAS antigens and host proteins has been shown at B and T cell level. However the identification of the autoantigens recognized by B and T cells within the inflammatory microenvironment of heart tissue in patients with RHD is still incompletely elucidated. In the present study, we used two-dimensional gel electrophoresis (2-DE) and mass spectrometry to identify valvular tissue proteins target of T cells from chronic RHD patients. We could identify three proteins recognized by heart infiltrating and peripheral T cells as protein disulfide isomerase ER-60 precursor (PDIA3), 78 kD glucose-regulated protein precursor (HSPA5) and vimentin, with coverage of 45%, 43 and 34%, respectively. These proteins were recognized in a proliferation assay by peripheral and heart infiltrating T cells from RHD patients suggesting that they may be involved in the autoimmune reactions that leads to valve damage. We also observed that several other proteins isolated by 2-DE but not identified by mass spectrometry were also recognized by T cells. The identified cardiac proteins are likely relevant antigens involved in T cell-mediated autoimmune responses in RF/RHD that may contribute to the development of RHD.

Selective depletion of Vβ2+CD8+ T cells in peripheral blood from rheumatic heart disease patients

Acute rheumatic fever (ARF) and its chronic valvular sequelae are the delayed consequence of a pharyngeal infection with group A Streptococcus (GAS). Several GAS proteins have been shown to be superantigens, raising the possibility that the expansion or deletion of T cells expressing specific Vβ regions might play a role in the pathogenesis of ARF or chronic rheumatic heart disease (RHD). We therefore analyzed by four-color flow cytometry, the Vβ repertoire on CD3, CD4 and CD8 T cells from four ARF patients, 10 RHD patients and also nine healthy controls. A selective depletion of Vβ2+ T cells was found only in the CD8 subset of chronic RHD patients. This is of interest since a number of GAS superantigens exert their effects on Vβ2+ cells and because only CD8+ T cells from ARF and RHD patients undergo anergy in response to GAS superantigens. Our results suggests that an ongoing immune process is present in RHD patients and that CD8+ T cells may have an important immunoregulatory role in the pathogenesis of the disease.

Restriction in the Usage of Variable β Regions in T-cells Infiltrating Valvular Tissue from Rheumatic Heart Disease Patients

Rheumatic Heart Disease (RHD) is a delayed consequence of a pharyngeal infection with group A streptococcus (GAS), usually ascribed to a cross-reactive immune response to the host's cardiac tissues. Several GAS proteins have been reported to be superantigens, also raising the possibility that T cells in RHD could be driven by superantigens. We therefore analysed the variable beta (Vβ) repertoire of T cells infiltrating heart valves from chronic RHD patients undergoing elective valvular surgery. We analysed 15 valve specimens from patients with longstanding quiescent RHD and control valves from four non-rheumatic individuals. Total RNA was extracted from fresh valve tissue and employed to amplify 22 Vβ genes by RT-PCR. In valvular tissue, a restricted number of only 2 to 9 Vβ regions were detected as opposed to the findings in control valves. In 8 RHD valves, the expression of Vβ1, 2, 3, 5.1, 7, 8, 9 or 14 was marked. These Vβ regions have been related to GAS superantigens. Our results evidence the presence of a restricted set of T lymphocytes in valvular tissue from a majority of patients with chronic RHD and suggest that valvular sequelae in these patients might be related to a local antigen or superantigen driven inflammatory process that persists even many years after the initial triggering event.

Molecular evidence for antigen-driven immune responses in cardiac lesions of rheumatic heart disease patients.

Rheumatic heart disease (RHD) is a sequel of post-streptococcal throat infection. Molecular mimicry between streptococcal and heart components has been proposed as the triggering factor of the disease, and CD4(+) T cells have been found predominantly at pathological sites in the heart of RHD patients. These infiltrating T cells are able to recognize streptococcal M protein peptides, involving mainly 1-25, 81-103 and 163-177 N-terminal amino acids residues. In the present work we focused on the TCR beta chain family (TCR BV) usage and the degree of clonality assessed by beta chain complementarity-determining region (CDR)-3 length analysis. We have shown that in chronic RHD patients, TCR BV usage in peripheral blood mononuclear cells (PBMC) paired with heart-infiltrating T cell lines (HIL) is not suggestive of a superantigen effect. Oligoclonal T cell expansions were more frequently observed in HIL than in PBMC. Some major BV expansions were shared between the mitral valve (Miv) and left atrium (LA) T cell lines, but an in-depth analysis of BJ segments usage in these shared expansions as well as nucleotide sequencing of the CDR3 regions suggested that different antigenic peptides could be predominantly recognized in the Miv and the myocardium. Since different antigenic proteins probably are constitutively represented in myocardium and valvular tissue, these findings could suggest a differential epitope recognition at the two lesional heart sites after a common initial bacterial challenge.

Lymphocyte Subsets and Plasma IL-1 α, IL-2, and TNF-α Concentrations in Acute Rheumatic Fever and Chronic Rheumatic Heart Disease

The distribution of CD3 +, CD4 +, CD8 +, CD19 +, CD16 +, and CD25 + lymphocyte populations in peripheral blood as well as the plasma concentrations of interleukin-1 α (IL-1 α), and IL-2 and tumor necrosis factor α (TNF-α) were investigated in 25 children with acute rheumatic fever (ARF) at the time of admission and after 3 months and in 15 children with chronic rheumatic heart disease (CRHD) and in 15 children with streptoccocal pharyngitis (SP) in order to determine changes in lymphocyte subsets and cytokine concentrations occurring during different stages of the disease. The percentages and absolute counts of CD4 +, CD16 +, CD25 + cells, the ratio of CD4/CD8 and plasma concentrations of IL-1 α and IL-2 in patients with ARF were significantly higher at admission than 3 months later. These levels were also significantly higher than in patients with CRHD, SP, or normal controls. Production of IL-2 in ARF and CRHD patients directly correlated with the percentages of CD4 + and CD25 + cells. According to our results, the evidences of increased cellular immune response in ARF are increased percentages CD4 + and CD25 + cells, CD4/CD8 ratio, and increased plasma concentrations of IL-1 α and IL-2. Furthermore, activation of cellular immune response was not present throughout all stages of rheumatic heart disease and also in SP.

Isolated atrial amyloidosis: A clinicopathologic study indicating increased prevalence in chronic heart disease

Congo red screening of 211 consecutive cardiac biopsy specimens obtained during cardiac surgery from 167 patients revealed 26 (16%) instances of isolated atrial amyloidosis (IAA). The ages of IAA-positive patients ranged from 25 to 52 years (mean age, 39 years). Twenty-three (88%) IAA-positive biopsy specimens were from patients with chronic rheumatic heart disease (CRHD) while three (12%) were from patients with an atrial septal defect (ASD). The prevalence of IAA in the CRHD patients was 23%, appreciably higher than that in the ASD patients (15%) and in other patients with atrial biopsies. The prevalence of IAA in both CRHD and ASD patients was significantly higher ( P < .001) than in controls. Controls consisted of 247 healthy adults who were autopsied after traumatic deaths, with an age range of 18 to 89 years (mean age, 38 years). Only seven (3%) control subjects were IAA positive; all were over 40 years of age. Isolated atrial amyloidosis deposits were permanganate resistant and immunohistochemically positive for human amyloid P (AP) protein and negative for human amyloid-associated (AA) protein and immunoglobulin light chains. They were observed as fine congophilic and birefringent deposits in intramyocardial vessel walls, along the myocardial sarcolemma, and in the subendocardium. There was associated myocyte hypertrophy but no atrophy. Electron microscopy demonstrated typical nonbranching amyloid fibrils. It is postulated that stretching of the atria in chronic heart disease results in a raised prevalence of IAA. Recent reports that IAA contains atrial natriuretic peptide, a polypeptide hormone product of atrial myocytes, supports this view.

Antibodies to a streptococcal cell wall adjuvant structure persist in patients with chronic rheumatic heart disease

Sera from 50 patients with chronic rheumatic heart disease were analysed by an enzyme linked immunosorbent assay for the presence of antibodies to the streptococcal minimal adjuvant moiety, muramyl dipeptide (MDP). The T-cell responsiveness to this structure was also studied in vitro, using the lymphocyte transformation test. Fifty four percent of the patients possessed anti-MDP antibodies in their sera when examined 5 to 25 years after the initial rheumatic attack. Such antibodies were found only in 5 to 6% of sera from healthy controls or from patients with cardiac disease of non-rheumatic origin. There was neither antigenic nor mitogenic stimulation by MDP of the T-cells from peripheral blood of chronic rheumatic heart disease patients or controls. The results point to a lifetime persistence of anti-MDP antibodies in rheumatic fever and rheumatic heart disease. Possible mechanisms by which detectable levels of such antibodies are maintained in rheumatic heart disease are discussed.