Tissue resident C reactive protein in degenerative aortic valves: correlation with serum C reactive protein concentrations and modification by statins.

OBJECTIVE: To assess aortic valve probes for valvar C reactive protein (CRP) presence, the relation between valvar and serum CRP, and a possible modification of CRP by statin medication. SETTING: Tertiary referral centre. PATIENTS AND DESIGN: End stage, degenerative valve tissue was taken from 81 patients, 57 with non-rheumatic aortic valve stenosis (AS) and 24 with degenerative aortic valve bioprosthesis (BP). Five non-stenosed valves served as controls. Tissue from four non-implanted bioprostheses was also examined. The presence and location of CRP was analysed by use of immunostaining and morphometry. Serum CRP concentrations were measured preoperatively. RESULTS: The majority of AS and BP valves exhibited CRP labelled cells, predominantly localised to the valvar fibrosa. The expression of CRP was much higher in BP than in AS (by a factor of 3.7, p = 0.03). Notably, non-stenosed aortic valves and non-implanted bioprostheses did not have CRP signalling. Serum CRP was also increased with BP (by a factor of 2.5, p = 0.02) and was significantly correlated with valvar CRP expression (r = 0.54, p < 0.001). The main finding in patients with (n = 26) and without statin treatment (n = 55) was that both valvar CRP expression (p = 0.02) and serum CRP concentrations (p = 0.04) were lower in the statin treated group. CONCLUSIONS: CRP was found in a large series of degenerative aortic valves, more often in bioprostheses than in native cusps. Serum CRP concentrations may reflect inflammatory processes within the aortic valve. The association of statin treatment with decreases in both valvar and serum CRP concentrations may explain known pleiotropic effects of statins in patients with aortic stenosis.

Do we still need CK-MB in coronary artery bypass grafting surgery?

AIM: The aim of this study was to evaluate the role of cardiac Troponin I (cTnI) and CK-MB for early prediction of outcome of patients undergoing coronary artery bypass grafting (CABG) surgery. METHODS: In 134 consecutive patients undergoing CABG-surgery blood samples were analyzed for cTnI concentration and CK-MB activity. ECG, hemodynamic parameters and the need for inotropic support, were continuously registered. Patients were divided into group A (uneventful course), group B (ischemia by ECG, hemodynamic stability) and group C (ischemia by ECG and IABP). RESULTS: After removal of X-clamp an increase cTnI and CK-MB was observed in all patients. Five hrs after stop of CPB group A (8.3+/-4.2 microg/L) had lower cTnI values compared to group B (14.8+/-5.3 microg/L) (p=0.035) and C (54+/-22.8 microg/L) (p=0.023). The cut off value was 14.8 microg/L. Sensitivity and specificity (99%/97%) was higher for cTnI than for CK-MB (90%/30%). The positive predictive value of outcome was better for cTnI (86%) than for CK-MB (33%). CONCLUSION: CTnI is a specific and sensitive marker for evaluation of perioperative myocardial ischemia (PMI). Additional determination of CK-MB activity does not provide further clinical information. CTnI should be the marker of first choice in CABG surgery.

[Chlamydia pneumoniae and cytomegalovirus in degenerative aortic valve stenoses]. / Chlamydia pneumoniae und Zytomegalie-Virus in degenerativen Aortenklappenstenosen.

Recent evidence suggests a causal relationship between inflammatory as well as infectious pathomechanisms and valvular degeneration. Based on the concept of chronic Chlamydia pneumoniae and cytomegalovirus (CMV) infections, and of variable stressors working on valvular microecology, the present study sought to assess the presence of the specific chlamydial heat shock protein (cHSP) 60, of CMV, of macrophages and of the human homologue hHSP60. Serial sections of high-grade degenerated native (n = 16) and prosthetic (n = 6) aortic valves were analyzed by immunohistochemistry for the presence of these determinants. Degenerated aortic valves revealed prevalence of Chlamydia pneumoniae in 41% (10 of 22) and CMV in 73% (16 of 22), while immunoreactive hHSP60 was present in 64% (14 of 22) and CD68 in 86% (19 of 22). Chlamydial HSP60, CMV and hHSP60 were predominantly found in valvular fibrosa; CMV showed a second predilection site at the ventricular luminal border. Both microorganisms revealed a strong correlation between each other (r = 0.73; p < 0.001) as well as with hHSP60 (cHSP60: r = 0.74; p < 0.001; CMV: r = 0.80; p < 0.001). Macrophage infiltration correlated with cHSP60 (r = 0.78; r < 0.001), CMV (r = 0.78; r < 0.001) and hHSP60 (r = 0.56; r = 0.007). Of note, the frequency of cHSP60, CMV and CD68 signaling was increased more than 5-fold in prosthetic valves compared to native valves (p = 0.017, p = 0.002 and p = 0.005). In summary, valvular infections of Chlamydia pneumoniae and of cytomegalovirus are frequently seen in degenerated aortic valves, irrespective of native or prosthetic origin. Colocalization of both HSP60 homologues and cytomegalovirus within macrophages in valvular fibrosa points to regional stressor effects that might be at least partly attributable to chronic persistent pathogen burden and molecular mimicry.

[Persistence of Chlamydia pneumoniae in coronary plaque tissue. A contribution to infection and immune hypothesis in unstable angina pectoris]. / Persistenz von Chlamydia pneumoniae in koronarem Plaquegewebe. Ein Beitrag zur Infektions- und Immunhypothese bei instabiler Angina pectoris.

BACKGROUND AND OBJECTIVE: There is an increasing number of pointers towards a causative connection between Chlamydia pneumoniae and atherosclerosis. But the pathogenetic mechanism and intimal structures that are involved remain unclear. Starting with the hypothesis of a chronic infection, as demonstrated by the presence of the chlamydial stress (heat-shock) protein 60 (HSP 60), the presence and localization of these bacterial products in coronary atheromas was investigated. PATIENTS AND METHODS: Coronary atheroma tissue from primary stenoses in 42 patients (36 men, 6 women, mean age 60.2 +/- 7.3 years) was studied immunohistochemically in the course of a retrospective analysis for chlamydial HSP 60. The findings in clinically acute coronary syndrome (Braunwald's classification) present in 27 patients were compared with those in 15 patients with acute angina and evaluated in relation to expression and site of predilection. RESULTS: An immune reaction to chlamydial HSP 60 was demonstrated in 27 of 42 atheromas (64%). Intact, non-atherosclerotic vessels, such as the mammary artery and sphenous vein, showed no such signals. Chlamydial HSP 60 was localized in maximally 23% of all plaque cells, mostly in macrophages/foam cells, more rarely in smooth muscle cells. Chlamydia in foam cells most often revealed ultrastructural patterns that pointed to the persistence of the pathogen. Sites of predilection of chlamydial HSP were predominantly foam cell areas and cell-poor regions, more rarely inflammatory infiltrates and areas of rupture. When comparing both types of lesion, signals for chlamydial HSP 60 were present in 21 of the 27 atheromas (78%) with unstable angina or acute myocardial infarction, but in only 6 of the 15 atheromas (40%) with stable angina. Within the group with the acute coronary syndrome, the prevalence of chronic chlamydial infection was independent of a previous myocardial infarction. CONCLUSIONS: Chlamydial HSP 60 can often be demonstrated in primary coronary stenosis of symptomatic patients. It is most frequently found in macrophages/foam cells and is highly prevalent in the acute coronary syndrome. In-situ findings suggest a pathogenetically relevant role of chronic persistent infection of Chlamydia pneumoniae in unstable coronary plaques.

[Chlamydia pneumoniae in coronary plaques: Increased detection with acute coronary syndrome]. / Chlamydia pneumoniae in koronarem Plaquegewebe: Vermehrter Nachweis bei akutem Koronarsyndrom.

BACKGROUND AND OBJECTIVE: There is seroepidemiologic and experimental evidence for a link between Chlamydia (C.) pneumoniae and arteriosclerosis. However, the clinical importance and the pathogenic pathways implicated remain unclear. In the present study, we sought to evaluate the presence and the location of C. pneumoniae in coronary atheroma, as well as a potential prevalence with unstable versus stable angina. PATIENTS AND METHODS: Retrospectively, coronary plaque material of primary lesions from 51 consecutive patients (44 men, 7 women, mean age 59.6 +/- 9.4 years) was examined for the presence of C. pneumoniae by use of immuno-histochemistry and transmission electron microscopy. The findings associated with clinically acute coronary syndrome according to Braunwald's classification (n = 31) were compared to those with stable angina (n = 20) and regarded for potential relations to characteristic intimal features. RESULTS: Immunoreaction for C. pneumoniae was found in 32 of 51 (63%) coronary plaques. Signals (% prevalence of specific intimal features) were present with necrotic areas (40%), sparse cellularity (40%), neo-vascularization (29%), thrombi (20%), ruptured plaque areas (19%), and fields rich in foam cells and calcifications (13%). Intimal hyperplasia and inflammatory infiltrates showed no signals. As the central finding in this report, C. pneumoniae immunoreaction was more frequently (P < 0.001) found in 26 of 31 (84%) lesions associated with unstable angina or acute myocardial infarction, compared to 6 of 20 (30%) lesions with stable angina (P < 0.001). Intact vessels devoid of arteriosclerotic disease, such as mammarial arteries and saphenous veins, were without C. pneumoniae signals (negative controls). Ultrastructurally, chlamydial elementary bodies were found in foam cells and phagocytosing macrophages, also in fragmented extracellular matrix adjacent to apoptotic and necrotic intimal cells. CONCLUSIONS: Chlamydiae pneumoniae were detected in 32 of 51 (63%) coronary primary lesions of symptomatic patients. Most importantly, there was a highly significant prevalence of lesions associated with acute coronary syndrome. Predilection sites of C. pneumoniae were areas that revealed small healing activity and (or) propensity to plaque rupture. The present in situ findings indicate a pathogenic role of Chlamydiae pneumoniae in human (coronary) plaque rupture.

Cardiac myxoma. Clinical and pathologic features in 15 cases.

Neoplasms are rare cardiac findings of which myxomas comprise about 75%. We report of 15 patients, predominantly female (60%) with a mean age of 58.8 years. Male patients (40%) were 20 years younger on average. 80% of these tumors developed in the left atrium fixed to the atrial septum. In 2 patients the right ventricle and in 1 patient the right atrium was involved. No left ventricular or bilateral tumors were found. Clinical findings showed a great variety of symptoms. Often misdiagnosis was established until echocardiography was performed. Major symptoms were dyspnea (80%), elevated erythrocyte sedimentation rate (73%), arrhythmias (53%), lung edema (47%), embolization (40%) and anemia (40%). Pathological examination and tumor genesis are still in discussion. Several theories are reported in literature: a true thrombus, thrombus organization with malignant potential, true neoplasms as well as a familiar myxoma complex may explain clinical and histological features. Our findings did not confirm only one theory but emphasize different possibilities.

[Myxoma of the heart: symptoms masked by an atrial septal defect]. / Myxom des Herzens. Maskierte Symptomatik bei Vorhofseptumdefekt.

A 68-year-old woman, known to have a secundum atrial septal defect which had been asymptomatic, reported dyspnea and occasional chest pain for two years. Admission examination revealed orthopnea, cyanosis, polycythemia and inflow congestion of the upper part of the body. After some blood-letting, nifedipine and nitrates brought immediate relief of symptoms. Physical examination, chest x-ray and ECG were not different from previously known findings. All laboratory tests were normal. The findings on cross-sectional echocardiography raised the suspicion of a right ventricular tumor, which was then demonstrated by computed tomography. There were no metastases. Under extracorporeal circulation a right-ventricular benign myxoma, attached to the apical septum and the size of a tennis-ball, was removed. The postoperative course was without complications and the patient was discharged symptom-free.