Morpho-functional changes of cardiac telocytes in isolated atrial amyloidosis in patients with atrial fibrillation.

Telocytes are interstitial cells with long, thin processes by which they contact each other and form a network in the interstitium. Myocardial remodeling of adult patients with different forms of atrial fibrillation (AF) occurs with an increase in fibrosis, age-related isolated atrial amyloidosis (IAA), cardiomyocyte hypertrophy and myolysis. This study aimed to determine the ultrastructural and immunohistochemical features of cardiac telocytes in patients with AF and AF + IAA. IAA associated with accumulation of atrial natriuretic factor was detected in 4.3-25% biopsies of left (LAA) and 21.7-41.7% of right (RAA) atrial appendage myocardium. Telocytes were identified at ultrastructural level more often in AF + IAA, than in AF group and correlated with AF duration and mitral valve regurgitation. Telocytes had ultrastructural signs of synthetic, proliferative, and phagocytic activity. Telocytes corresponded to CD117+, vimentin+, CD34+, CD44+, CD68+, CD16+, S100-, CD105- immunophenotype. No significant differences in telocytes morphology and immunophenotype were found in patients with various forms of AF. CD68-positive cells were detected more often in AF + IAA than AF group. We assume that in aged AF + IAA patients remodeling of atrial myocardium provoked transformation of telocytes into "transitional forms" combining the morphological and immunohistochemical features with signs of fibroblast-, histiocyte- and endotheliocyte-like cells.

Antiphospholipid Antibodies and Heart Valve Disease in Systemic Lupus Erythematosus.

Evaluation of antiphospholipid antibodies (aPL) and correlation with heart valve abnormalities among patients with systemic lupus erythematosus (SLE). Nested case-control study was conducted with 70 patients with SLE selected from a longitudinal database based on levels of aPL and presence or absence of valve disease by echocardiogram. Valvular abnormalities observed were regurgitation (52), other (14), artificial valves (4), stenosis (2), thickening (2) and no Libman-Sacks endocarditis (0). The mitral valve was the most commonly affected (30 abnormalities), followed by the tricuspid (20 abnormalities). Multivariate logistic regression for those with and without an aPL value ≥20 units/mL, adjusted for disease duration and age, showed significant differences for any valve abnormality (odds ratio [OR] = 3.1; 95% CI: 1.0-8.9; P = 0.041) and individually for the tricuspid valve (OR = 3.3; 95% CI: 1.0-11.1; P = 0.052) but not for the mitral valve (OR = 2.1; 95% CI: 0.68-6.45; P = 0.195). Levels of aPL ≥20 units/mL showed no association with aortic (P = 0.253), pulmonic (P = 1.000), tricuspid (P = 0.127), or mitral (P = 0.249) valve abnormalities. Levels of aPL correlate with certain valvular abnormalities among patients with SLE.

The association between systemic lupus erythematosus and valvular heart disease: an extensive data analysis.

BACKGROUND: Association between antiphospholipid syndrome in systemic lupus erythematosus (SLE) and valvular heart disease (VHD) is well reported, but relatively few studies have been carried out to establish the linkage between VHD and SLE itself. We aimed to investigate link between VHD and SLE and to evaluate the association of diverse factors with VHD among these patients in a large-scale population-based study. MATERIALS AND METHODS: We used the databases of the largest state-mandated health service organization in Israel. All SLE patients were included (n = 5018) as well as their age and sex-matched controls (n = 25 090), creating a cross-sectional population-based study. Medical records of all subjects were analysed for documented VHD and the presence of antiphospholipid antibodies (aPLs). A logistic regression model was carried out to evaluate the diverse factors including SLE and aPLs as independent risk factors for VHD. RESULTS: Valvular heart disease were found to be more frequent among SLE group when compared to controls (aortic stenosis, 1·08% vs. 0·35% respectively, P < 0·001; aortic insufficiency, 1·32% vs. 0·29% respectively, P < 0·001; mitral stenosis, 0·74% vs. 0·21% respectively, P < 0·001; mitral insufficiency, 1·91% vs. 0·39% respectively, P < 0·001). Male sex, hypertension, aPLs and SLE were found to be significant independent risk factors for VHD. CONCLUSION: All VHD are more prevalent among SLE patients when compared to controls. SLE and aPLs are independent risk factor for VHD (OR of 2·46 and 1·7, respectively). Physicians must be aware of such significant association, and routine echocardiography should be considered in SLE patients regardless of their aPL status.

A Rare Case of Florid Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis Involving Both Atrioventricular Valves.

Cardiac involvement is rare in antineutrophil cytoplasmic autoantibody (ANCA)-associated systemic vasculitis but can involve aortic and mitral valves. We present an unusual case of a 65-year-old woman who presented 16 years after an aortic valve replacement with severe mitral regurgitation with ACNA-associated vasculitis. The extensive nature of the pathologic condition, which extended to the tricuspid valve, prevented the replacement of the mitral valve during a surgical procedure. This is a rare case in which florid valvulopathy was observed in association with vasculitis.

Immunological and inflammatory processes in systemic autoimmune disease may not only cause pericardium inflammation, but may also cause mitral valve deterioration and left ventricular wall thickening.

PURPOSE: Systemic autoimmune disease (SAD) frequently affects the pericardium, and pathology is characterized by both immunological and inflammatory processes. We hypothesized that these processes simultaneously influence mitral-valve (MV) deterioration and left-ventricular (LV) wall thickening in SAD subjects. METHODS: 101 SAD subjects were selected (76 female; 53±17years; systemic-lupus-erythematosus, 26%; vasculitis, 20%; scleroderma, 14%; polymyositis/dermatomyositis complex, 10%; mixed connective tissue disease, 11% and rheumatoid-arthritis, 2%). MV anterior-mitral-leaflet (AML) length, AML thickness index, AML doming height and LV mass index (LVMI) were measured using transthoracic-echocardiography (TTE) and the presence of MV calcification, MV sub-valvular thickening and pericardial effusion (PE) were estimated. AML thickness index was calculated as the ratio of AML thickness to aortic posterior wall thickness. The correlation between LVMI and ECG V1S+V5R voltage was used to assess the etiology of LV wall thickening. RESULTS: 19 subjects (19%) had significant PE. PE subjects had a significantly greater AML thickness index (1.55±0.48 vs. 1.14±0.32, P<0.001), AML doming height (1.26±1.54mm vs. 0.03±0.91mm, P<0.001), more frequent MV sub-valvular thickening (26% vs. 5%, P=0.003) and greater LVMI (104.7±34.6g/m2 vs. 80.6±21.0g/m2, P=0.002). Significant correlation was observed between LVMI and ECG V1S+V5R voltage in 79 subjects without PE (R=0.39, P<0.001). However, in 18 subjects with PE, no such correlation was observed (R=0.30, P=0.23). CONCLUSIONS: MV, MV sub-valvular deterioration and increased LVMI, unrelated to high voltage ECG criteria, were frequently detected in SAD subjects with PE. Immunological and inflammatory processes in SAD may not only cause pericardium inflammation, but may also cause MV deterioration and LV wall thickening.

Recurrent mitral valve regurgitation with neutrophil infiltration in a patient with multiple aseptic abscesses.

Aseptic abscess (AA) is characterized by accumulation of neutrophils without evidence of infection, no response to antibiotics, and rapid response to corticosteroids. We report a case of multiple abscesses in the subcutaneous tissues and joints, and severe mitral valve regurgitation. Although AA did not respond to antibiotic therapy, it improved dramatically with corticosteroid treatment. However, repeated valvuloplasty was required for the mitral valve regurgitation. The mitral valve tissue showed neutrophil infiltration without any bacterial invasion. This is the first case of AA to show involvement of cardiac valves, indicating the importance of systematic examination for patients with AA and cardiac valve involvement.

Antiphospholipid syndrome and rheumatic fever: a case spanning three decades of changing concepts and common immunological mechanisms.

We present a case of primary antiphospholipid syndrome (APS), initially diagnosed as acute rheumatic fever, resulting in severe mitral valve incompetence. This case raises questions of the specificity of the Jones diagnostic criteria for rheumatic fever in a population where it is infrequently encountered. There are similarities in clinical, pathological and echocardiographic presentations between rheumatic fever and APS, in addition to common immunological mechanisms. Our case highlights the possibility that rather than rheumatic fever being primarily responsible for her recurrent attacks of chorea and arthritis, the streptococcal infections in our patient occurred either in the setting of underlying antiphospholipid antibodies ('second hit' phenomenon), or may have triggered the development of pathogenic antibodies (molecular mimicry), subsequently leading to the clinical evolution of APS. During the three decades of our patient and her recurrent problems, there has been an evolving knowledge of the mechanisms of APS and rheumatic fever, allowing us to extend our understanding beyond symptoms and syndromes, to a better realization of the underlying immunological relationship between the two.

Regulated upon activation, normal T-cell expressed and secreted chemokine and interleukin-6 in rheumatic pulmonary hypertension, targets for therapeutic decisions.

BACKGROUND: Recent studies have highlighted the possible influence of chemokines and cytokines on several types of pulmonary arterial hypertension (PAH). Increasing interest has also been focussed on their role as a cause of post-cardiopulmonary bypass (CPB) organ dysfunction. HYPOTHESIS: Chemokines and cytokines are involved in the pathobiology of rheumatic PAH. METHODS: Serum levels of the chemokine, regulated upon activation, normal T-cell expressed and secreted (RANTES) and the cytokine interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA) in 35 patients with rheumatic mitral valve disease and 10 matched healthy subjects (control group). Eleven patients (31.4%) had severe pulmonary hypertension. Subsequently, 23 patients underwent mitral valve replacement. The relation of RANTES and IL-6 circulating level with postoperative organ dysfunction was analysed through multiple organ dysfunction score (MODS). RESULTS: Patients with severe PAH have a significantly higher mean serum level of RANTES compared with other patients (6138.6+/-3543.8 pg/ml vs 1818.2+/-475.2 pg/ml, p=0.0003). The serum level of IL-6 in the patients was statistically different from that of the control (378+/-50.8 pg/ml vs 262+/-90.5 pg/ml, respectively, p=0.002). Patients who required postoperative inotropes had higher preoperative and post-CPB levels of both RANTES and IL-6. While patients with postoperative lung dysfunction had higher levels of IL-6 preoperatively and post-CPB and lower levels of RANTES post-CPB. CONCLUSIONS: RANTES and IL-6 should be investigated as potential therapeutic targets in the control of rheumatic PAH. Improved understanding of the contribution of RANTES and IL-6 to adverse postoperative complications can lead to improved patient outcome.

Hypocomplementemic urticarial vasculitis with Jaccoud's arthropathy and valvular heart disease: case report and review of the literature.

We describe a female Japanese patient with concomitant hypocomplementemic urticarial vasculitis, Jaccoud's arthropathy and valvular heart disease. In 1996, she developed arthritis with swelling of both proximal interphalangeal joints and urticarial vasculitis on both arms that was resolved by administration of glucocorticoid (prednisolone 30 mg/day). Tests for antineutrophil cytoplasmic antibodies, antinuclear antibody and rheumatoid factor gave negative results. The findings of a skin biopsy examination were consistent with 'leukocytoclastic vasculitis'. During 10 years of observation, the patient manifested polyarthritis leading to progressive deformity of the joints of the hands and feet (without loss of cartilage or erosion of bone), persistent urticaria exacerbated by cold and accompanied by hypocomplementemia and progressive cardiac valvular disease with mitral valve regurgitation. There are only three reports described previously documenting five patients with this rare combination of manifestations.

Infective endocarditis caused by lactobacillus.

Lactobacillus (LB) is a gram-positive rod-shaped bacterium that inhabits the oral cavity, gastrointestinal tract, vagina and nasal cavity. Although LB plays a role in the prevention of infections caused by pathogenic bacteria, it causes some critical infectious diseases such as infective endocarditis (IE). IE due to LB is rare; however, early diagnosis and early treatment are important because of its high mortality rate. We report the onset of IE after otologic treatment in a heavy drinker of alcohol, the second case of IE due to LB in Japan.

[The role of cytokines in the development of endothelial dysfunction in simple cardiac anomalies].

One hundred and twenty patients aged 18 to 32 years with echocardiographically verified simple cardiac anomalies (SCA) within the framework of non-differentiated connective tissue dysplasia (CTD). Immune-enzyme assay was used to measure serum levels of cytokines taking part in the regulation of endothelial function, such as the main factor of fibroblast growth, interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). The study revealed that the levels of fibroblast growth factor and IL-1beta were increased, while the serum levels of TNF-alpha and IFN-gamma were lowered. The alterations were most evident in cases of multiple SCA, myxomatous degeneration of a prolapsing mitral valve, and mitral regurgitation of higher than I degree. The determination of cytokine profile in patients with SCA may be used to stratificate the risk of cardiovascular complications in the heterogenous group of patients with nondifferentiated CTD.

Impact of serum C-reactive protein elevation on the left ventricular spherical change and the development of mitral regurgitation after anterior acute myocardial infarction.

BACKGROUND/AIMS: Mitral regurgitation (MR) is frequently observed in patients with acute myocardial infarction (AMI), and is known to convey an adverse prognosis. We sought to clarify the relationship between MR and left ventricular (LV) remodeling, in association with serum C-reactive protein (CRP) elevation. METHODS/RESULTS: A total of 181 patients with first anterior ST-elevation AMI were examined. MR was detected in 68 patients by color Doppler echocardiography 2 weeks after AMI, and the patients with MR were associated with higher incidence of readmission for heart failure. Serum CRP was serially measured, and the peak serum CRP level was markedly increased in patients with MR compared with those without MR. Multiple logistic regression analysis showed that peak CRP tertile was an independent determinant of MR after AMI (p < 0.0001). In the substudy, the increases in LV end-diastolic volume and sphericity index were higher in patients with MR than in those without MR. CONCLUSIONS: MR during the early phase of anterior AMI was associated with LV spherical change and late-phase heart failure, in association with increased serum CRP level. These findings suggest an important role of the inflammatory response in the development of ischemic MR and LV remodeling.

Relationship of antiphospholipid antibodies to cardiovascular manifestations of systemic lupus erythematosus.

OBJECTIVE: Although antiphospholipid antibodies (aPL) are associated with arterial and venous thrombosis in systemic lupus erythematosus (SLE), the extent to which they influence other cardiovascular manifestations is either controversial or uncertain. We undertook this study to examine the relationships of aPL with valvular, myocardial, and arterial disease in SLE. METHODS: Two hundred patients in an SLE registry, recruited at the time of outpatient visits, underwent comprehensive interviews, physical examinations, laboratory assessments, echocardiography to assess left ventricular (LV) and valvular status, carotid ultrasonography to detect atherosclerosis (discrete plaque), and radial applanation tonometry to measure arterial stiffness. RESULTS: Antiphospholipid antibodies were present(defined as IgG or IgM anticardiolipin > or =40 IU/ml or the presence of lupus anticoagulant) in 42 patients (21%). Mitral valve nodules and moderate-to-severe mitral regurgitation were more common in aPL-positive patients (both 14.3% versus 4.4%; P = 0.02). Thirty-one percent of patients with high titers of IgG aPL (>80 IU/ml) had mitral valve nodules, compared with 20% of patients with mildly to moderately elevated levels of IgG aPL (16-80 IU/ml) and 4% of patients without IgG aPL (overall P < 0.001). Levels of soluble tumor necrosis factor receptors were higher in the presence of both aPL and mitral valve nodules. LV dimensions, systolic function, and carotid artery stiffness as well as prevalences of Raynaud's phenomenon, pulmonary hypertension, and atherosclerosis were similar in aPL-positive and aPL-negative patients. CONCLUSION: Antiphospholipid antibodies in SLE are associated with mitral valve nodules and significant mitral regurgitation, possibly due to valvular endothelial cell activation. However, in this population, they are not associated with evidence of myocardial hypertrophy, systolic dysfunction, coronary or carotid atherosclerosis, or other vascular abnormalities.

HLA class II associations with rheumatic heart disease among clinically homogeneous patients in children in Latvia.

Genetic control of immune reactions has a major role in the development of rheumatic heart disease (RHD) and differs between patients with rheumatic fever (RF). Some authors think the risk of acquiring RHD is associated with the HLA class II DR and DQ loci, but other views exist, due to the various HLA-typing methods and ways of grouping cases. Our goal was to determine the relations between HLA class II alleles and risk of or protection from RF in patients with relatively homogeneous clinical manifestations. A total of 70 RF patients under the age of 18 years were surveyed in Latvia. HLA genotyping of DRB1*01 to DRB1*18 and DQB1*0201-202, *0301-305, *0401-402, *0501-504, and *0601-608 was performed using polymerase chain reaction sequence-specific primers. Data for a control group of 100 healthy individuals typed for HLA by the same method were available from the databank of the Immunology Institute of Latvia. Of the RF patients, 47 had RHD and 8 had Sydenham's chorea. We concluded that HLA class II DRB1*07-DQB1*0401-2 and DRB1*07-DQB1*0302 could be the risk alleles and HLA class II DRB1*06 and DQB1*0602-8, the protective ones. Patients with mitral valve regurgitation more often had DRB1*07 and DQB1*0401-2, and patients with multivalvular lesions more often had DRB1*07 and DQB1*0302. In Sydenham's chorea patients, the DQB1*0401-2 allele was more frequent. Genotyping control showed a high risk of RF and RHD in patients with DRB1*01-DQB1*0301-DRB1*07-DQB1*0302 and DRB1*15-DQB1*0302-DRB1*07-DQB1*0303.

HLA-B27 positive juvenile arthritis with cardiac involvement preceding sacroiliac joint changes.

While cardiovascular disease develops in up to 50% of adult patients with ankylosing spondylitis, it is very uncommon in its juvenile counterpart. Regarding the early stage of the disease, before onset of sacroiliac joint changes, only two cases with aortic incompetence have been published while reports of mitral valve involvement are not available. A 13 year old boy is described with an HLA-B27 positive asymmetric oligoarthritis and enthesitis, without back pain or radiographic evidence of sacroiliitis. Echocardiography showed an echogenic structure measuring 8 x 11 x 20 mm at the fibrous continuity between the aortic and mitral valves extending through a false tendon into an echogenic thickened posterior papillary muscle, causing a grade II aortic and grade I/II mitral regurgitation. Short term corticosteroid and long term non-steroidal anti-inflammatory drug and disease modifying antirheumatic drug treatments efficiently controlled the symptoms. The cardiac findings remained unchanged during a follow up of 20 months. Careful cardiac evaluation appears to be mandatory even in these young patients.

Cardiac involvement in Behçet's disease.

To assess the prevalence and the extent of cardiac involvement in patients with Behçet's disease and to investigate the possible causes that may predispose to this involvement, 30 patients affected by Behçet's disease and 30 normal control subjects were submitted to M-mode, two-dimensional, and Doppler echocardiographic evaluation. Moreover, antinuclear and anticardiolipin autoantibodies were determined in the sera of both patients and control subjects. Finally, HLA-B51 positivity was assessed in the patients and in a historical control group. Mitral valve prolapse was observed in 50% and proximal aorta dilatation in 30% of the patients. There was a significant difference in the rate of these abnormalities in comparison with the control group. Left ventricular function parameters were similar between the two groups. The positivity rate of antinuclear and anticardiolipin autoantibodies was very low (7%), without differences between the groups. HLA-B51 was detected in 82.7% of the patients versus 21.7% in the control group (p < 0.00001). In conclusion, this study demonstrates a high rate of cardiac abnormalities in patients with Behçet's disease.

Mitral regurgitation may be related with previous streptococcal infection.

UNLABELLED: We measured anti M protein antibody (AMPA) titres in children with idiopathic mitral regurgitation (MR), streptococcal infection, rheumatic fever (RF), post-streptococcal acute glomerulonephritis (AGN) and normal healthy children. We investigated the association of MR with streptococcal infection and whether high AMPA titres can be used as persisting evidence of previous streptococcal infection. AMPA titres were measured with an enzyme-linked immunosorbent assay. We found significantly higher antibody titres in patients with MR and in streptococcal infection, RF, and AGN than in healthy controls. In the MR group (n = 15), 54% patients had AMPA titres above the 90th percentile value that was found in normal controls. An elevated AMPA titre persisted for a long period even when the anti-streptolysin O titres had declined to normal in RF patients. Our data suggest that the high AMPA titres in MR should be further investigated to clarify the probable association with previous streptococcal infection. CONCLUSION: High AMPA titre is a risk factor for developing complications after streptococcal infection. Our serological evidence suggests that in some patients, MR may be related to previous streptococcal infection.

Prevalence of anticardiolipin antibody in isolated mitral or aortic regurgitation, or both, and possible relation to cerebral ischemic events.

Anticardiolipin antibodies (acLa) are associated with a thrombotic tendency (often involving cerebral ischemic events), are frequently present with systemic lupus erythematosus and have been found together with cardiac valve abnormalities. Previous studies evaluated patients characterized by the presence of acLa or lupus, precluding assessment of the frequency of acLa in those with valvular disease. This study aims to establish the prevalence of acLa in patients with valve disease in the absence of lupus and, furthermore, to determine the influence of acLa on the risk of cerebral events in valve disease. Eighty-seven consecutive patients with mitral or aortic regurgitation, or both, prospectively underwent enzyme-linked immunosorbent assay testing for immunoglobulin G (IgG) and M acLa, as did 24 normal subjects. AcLa values greater than or equal to 3 SD above the normal mean were considered "positive." Prior cerebral events were defined retrospectively. Of 87 patients with valvular disease, 26 had positive IgG acLa levels compared with 0 of 24 normal subjects (p less than 0.01). AcLa values did not vary with valve disease etiology. Focal cerebral events had occurred in 8 patients and were embolic or probably embolic in 7, including 7 of 26 IgG acLa-positive and 1 of 60 IgG acLa-negative patients (p less than 0.001). In the absence of lupus, IgG acLa is highly prevalent among patients with aortic or mitral regurgitation, or both; this association may indicate a relatively high risk for cerebral emboli.

Association of antibodies against phospholipids with heart valve disease in systemic lupus erythematosus.

A prospective echocardiographic study was carried out on 132 consecutive patients with systemic lupus erythematosus (SLE) derived from three European university medical centres. The prevalence of valvular lesions in patients with SLE was 22.7% compared with 2.9% in a control group of 68 healthy volunteers. 50 SLE patients had antibodies against phospholipids. The prevalence of valve vegetations (8/50 [16%]) and of mitral regurgitation (19/50 [38%]) was significantly higher among the SLE patients with antiphospholipids than among those without (1 and 10/82 [1.2% and 12%], respectively). During follow-up of the patients with valvular lesions, haemodynamically significant clinical valve disease developed in 6 but surgery was required in only 1; 9 had cerebrovascular occlusions; and 7 died, although no death was due directly to the cardiac involvement. Thus, valvular heart disease, particularly affecting the mitral valve, is common in patients with SLE, and the presence of antibodies against phospholipids is associated with a higher prevalence of valvular abnormalities in these patients.