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Signs of inflammation in different types of heart valve disease: The VOCIN study
Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Heart valve dysfunction is a relatively common condition in the population, whereas significant heart valve disease is more unusual. The cause of different types of heart valve disease depends on which valve is concerned. Rheumatic heart valve disease, has for a long time been considered to constitute a post-inflammatory condition. During the 1990s it was also shown that the so-called non-rheumatic or degenerative tricuspid aortic stenosis, comprised signs of inflammation.

In this study, 118 patients (the VOCIN study group) referred to the University Hospital for preoperative investigation due to significant heart valve disease, were examined regarding signs of inflammation.

Twenty-nine aortic valves from patients with significant aortic stenosis were divided into tricuspid and bicuspid aortic valves. The bicuspid aortic stenotic valves revealed signs of inflammation to a similar extent as the tricuspid valves. However, the tricuspid and bicuspid valves differed regarding distribution of calcification. In contrast, inflammation was not a predominant feature in 15 aortic and mitral valves from patients with significant heart valve regurgitation.

Gross valvular pathology consistent with rheumatic aortic stenosis was found in 10 patients. These valves revealed a somewhat lower degree of inflammatory cell infiltration, but on the whole, there were no substantial differences when compared to non-rheumatic aortic stenotic valves. They did, however, reveal a similar distribution of calcification as the bicuspid, non-rheumatic aortic valves.

The VOCIN study group was compared to an age- and gender matched control group with regard to history and signs of rheumatic disease. There was not any increased prevalence of clinical manifestations of non-cardiac inflammatory disease in patients with significant heart valve disease, when compared to healthy control subjects. However, patients with heart valve disease had significantly increased serum levels of inflammatory markers compared to controls. The increase in inflammatory markers remained significant even in the subgroup of non-rheumatic aortic stenosis devoid of coronary artery disease. These results indicate that a systemic inflammatory component is associated with stenotic, non-rheumatic heart valve disease.

The similarities between different forms of calcific aortic valve disease indicate a similar pathogenesis. The question is raised whether aortic stenosis is one disease, mainly caused by a general and non-specific response to dynamic tissue stress due to an underlying malformation of the valve.

Place, publisher, year, edition, pages
Institutionen för medicin och hälsa , 2008. , 55 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1052
Keyword [en]
Heart valve dysfunction, heart valve disease, VOCIN study group, aortic valves, Gross valvular pathology
National Category
Dentistry
Identifiers
URN: urn:nbn:se:liu:diva-11330ISBN: 978-91-7393-949-2 (print)OAI: oai:DiVA.org:liu-11330DiVA: diva2:17737
Public defence
2008-04-18, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2008-03-18 Created: 2008-03-18 Last updated: 2009-08-22
List of papers
1. T lymphocyte infiltration in non-rheumatic aortic stenosis: a comparative descriptive study between tricuspid and bicuspid aortic valves
Open this publication in new window or tab >>T lymphocyte infiltration in non-rheumatic aortic stenosis: a comparative descriptive study between tricuspid and bicuspid aortic valves
2002 (English)In: Heart, ISSN 1355-6037, Vol. 88, no 4, 348-351 p.Article in journal (Refereed) Published
Abstract [en]

Background: The two most common causes of aortic stenosis are primary "degenerative" calcification of tricuspid aortic valves and secondary calcification of congenital bicuspid valves. T lymphocyte infiltration occurs in stenotic tricuspid aortic valves, indicating an inflammatory component, but it has not been shown whether it also occurs in stenotic bicuspid valves.

Objective: To compare non-rheumatic tricuspid and bicuspid stenotic aortic valves for the presence and distribution of T lymphocytes.

Setting: University hospital.

Patients and design: Valve specimens were obtained from 29 patients (15 women, 14 men, mean age 69 years (range 52–81 years)), referred to the hospital for aortic valve replacement because of symptomatic aortic valve stenosis. There were 17 tricuspid valves (from 10 women and seven men, mean age 71 years) and 12 bicuspid valves (from five women and seven men, mean age 67 years). To identify mononuclear inflammatory cells, sections were stained with antibodies for CD3 (pan-T cell antigen, Dako 1:400) and then graded histologically according to the degree of T cell infiltrate.

Results: T lymphocyte infiltration was present in both tricuspid and bicuspid stenotic aortic valves, without any significant differences in extent or localisation.

Conclusions: Stenotic bicuspid aortic valves show the same degree of T lymphocyte infiltration as degenerative tricuspid aortic valves. Inflammation needs to be considered in the pathogenesis of acquired aortic stenosis, irrespective of the primary valve anomaly.

Keyword
aortic valve stenosis, pathology, lymphocytes, inflammation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13046 (URN)10.1136/heart.88.4.348 (DOI)
Available from: 2008-03-18 Created: 2008-03-18 Last updated: 2009-08-21
2. Role of inflammation in non-rheumatic, regurgitant heart valve disease: A comparative, descriptive study regarding apolipoproteins and inflammatory cells in non-rheumatic heart valve disease
Open this publication in new window or tab >>Role of inflammation in non-rheumatic, regurgitant heart valve disease: A comparative, descriptive study regarding apolipoproteins and inflammatory cells in non-rheumatic heart valve disease
2007 (English)In: Cardiovascular pathology, ISSN 1054-8807, E-ISSN 1879-1336, Vol. 16, no 3, 171-178 p.Article in journal (Refereed) Published
Abstract [en]

Background: Nonrheumatic aortic stenosis is the predominant cause of heart valve surgery in the Western world. Aortic and mitral regurgitation account for a lesser amount of the heart valve surgery. During the 1990s, inflammatory cell infiltrates have been demonstrated in nonrheumatic stenotic aortic valves. These findings suggest an inflammatory component in the pathogenesis of nonrheumatic aortic valve stenosis. However, nonrheumatic regurgitant aortic and mitral valves have not been investigated in this respect. The aim of this study was to compare nonrheumatic regurgitant aortic and mitral valves with stenotic aortic valves regarding the presence of T lymphocytes, macrophages, apolipoprotein B, and apolipoprotein A-I.

Methods: Valve specimens were obtained from 42 patients referred to hospital for surgery because of significant heart valve disease. From these patients, 29 aortic stenotic valves, 9 aortic regurgitant, and 6 mitral regurgitant valves, all nonrheumatic, were obtained for the study. Fourteen valves collected from subjects undergoing clinical/medicolegal autopsy were used as control. In order to identify mononuclear inflammatory cells and apolipoproteins, sections were investigated with immunohistochemical analyses and then categorized semiquantitatively.

Results: Regurgitant and control valves showed a significantly lower degree of inflammatory cell infiltrate and a lower degree of apolipoprotein deposition as compared to stenotic aortic valves.

Conclusions: The signs of inflammation seen in nonrheumatic aortic stenosis are not prominent features in the nonrheumatic, regurgitant valves. This is consistent with the multi-factorial pathogenesis of these conditions.

Keyword
Aortic valve regurgitation, Mitral valve regurgitation, T Lymphocytes, Apolipoproteins
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13047 (URN)10.1016/j.carpath.2006.10.004 (DOI)
Available from: 2008-03-18 Created: 2008-03-18 Last updated: 2017-12-13
3. Inflammatory characteristics of aortic stenotic valves: a comparison between rheumatic and non-rheumatic aortic stenosis
Open this publication in new window or tab >>Inflammatory characteristics of aortic stenotic valves: a comparison between rheumatic and non-rheumatic aortic stenosis
2008 (English)Article in journal (Refereed) Submitted
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13048 (URN)
Available from: 2008-03-18 Created: 2008-03-18
4. History and signs of rheumatic disease in patients with significant heart valve disease
Open this publication in new window or tab >>History and signs of rheumatic disease in patients with significant heart valve disease
Show others...
2008 (English)Article in journal (Refereed) Submitted
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13049 (URN)
Available from: 2008-03-18 Created: 2008-03-18

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