Degenerative Aortic Valve Disease, its Mechanism on Progression, its Effect on the Left Ventricle and the Postoperative Results

Wilhelm Peter Mistiaen

• Publisher: Bentham Science Publishers
• Print ISBN: 9781608056057
• eBook ISBN: 9781608052875
• Topic: Medicine
• Subtopic: Cardiology

Degenerative aortic valve disease is the most prominent cardiac valve disease in Western societies. This volume describes some of the more important issues and problems for this condition:
its progressive character and the underlying mechanisms of this progression
diagnostic difficulties 1) ascertainment of valvular origin of symptoms in elderly; 2) the challenge of the low output – low gradient syndrome; 3) moderate aortic valve calcification during CABG; 4) prediction of the rate of progression (who will need surgery on short term and who not).
the burden on the left ventricle and its consequences (danger of postponement of surgery)
the effect and the modalities (access, types of valves) of surgical treatment on survival (and QoL)
the mode of registering postoperative complications
determining predictors for valve related, non-valve related cardiac and non-cardiac postoperative complications
The e-book is a unique presentation, specific to degenerative aortic valve disease and its treatment including information about ways to deal with the progressive character of the disease (autophagy as a mode of cell death). Cardiologists still avoid or delay referring patients to the surgeon for the sake of age, left ventricular function or co-morbidity. Therefore, the e-book benefits readers by addressing the above issue and providing critical information for changing referral policy, which would ultimately enhance postoperative survival of patients suffering from heart valve disease.

Pathology of CAVS

Abstract

The pathological changes in CAVS are much more than a simple age related “wear and tear”. There is some resemblance of CAVS with atherosclerosis, but important differences have also been authenticated. Both conditions share a number of risk factors, however

The mechanisms leading to the microscopically observable changes in CAVS include many molecules and pathways. There is a considerable “cross talk” between these mechanisms which makes their description difficult.

The unravelling of these pathways requires a description in layers.

The outer layer consists of the risk factors of which the most common are lipid disorders and hypertension.

The middle layer consists of the molecules and mediators involved. Some of these molecules are inflammatory, others are the result of mechanical or oxidative stress, still others play a role in the remodelling of the ECM.

The inner layer consists of the mechanisms, which are inflammation, calcification or ossification, angiogenesis, remodelling of the ECM and programmed cell death.

The unravelling of these processes in CAVS is an ongoing process and is still not completely understood. This understanding might have some consequences in terms of prevention or slowing down of the process.

Keywords: : Angiotensin, apoptosis, atheromatosis, autophagy, calcification, Heyde’s syndrome, inflammation, lipid infiltration, mechanical stress, neo-angiogenesis, osteoblastic differentiation, oxidative stress, vitamin K antagonists.

1.. The incidence and the natural history of CAVS

CAVS is the most frequent heart valve disease in industrialised countries today and its prevalence acutely increases with age: the prevalence in patients over 65 years is estimated at 2%. An additional 29% have aortic valve sclerosis, i.e., thickening and calcification and cuspal thinning of a trileaflet aortic valve in the absence of ventricular outflow obstruction [1, 2]. Hence, with the lengthening of life expectancy, the population of elderly patients with CAVS is expected to increase in the future. AVR still is the reference treatment for severe symptomatic CAVS and there are no explicit restrictions for intervention related to age itself. The number of operations also increases. However, the decision to operate is often difficult in old patients in whom it may not be obvious whether or not the benefit of surgery, compared to spontaneous outcome, outweighs the risk of intervention. The published results of AVR for CAVS in elderly could serve as a standard for comparison and decision making for alternatives such as medical treatment, BAV or TAVI [1].

The natural history of CAVS was highlighted half a century ago [1, 3]. When symptoms and certainly signs of CHF appear, compensatory mechanisms that maintain an adequate circulation get exhausted. Life expectancy decreases drastically from that moment on. Based on these observations, AVR should be recommended. However, the extrapolation of these findings to the elderly with CAVS may be debatable. In Ross and Braunwald’s study, death occurred at an average age of 63. A more contemporary series of elderly patients with severe CAVS showed that there still is a wide range of survival rates in non-operated patients. The three predictive factors of poor spontaneous outcome were NYHA functional class III or IV, associated mitral regurgitation, and LV systolic dysfunction. The combination of these three factors has identified a subgroup at particularly high risk, with a 3 year survival rate of only 20%. On the other hand, the 3 year survival was over 80% in patients who did not have any of these three factors [1].

Hemodynamic progress has also been described. In CAVS, the obstruction to LVOT leads to a gradual increase in TVG. This reaches levels of 100 mm Hg in severe cases. This corresponds to an AVA of 0.5-1 cm². Cardiac output can be maintained by the development of LVH. Eventually, CHF may develop. This emphasizes on the deleterious effect of chronic pressure overload on the myocardial cells [2].

2.. Macroscopic and microscopic description of the diseased valve

When valves are excised during surgery, they show a variety of pathological changes, macroscopically as well as microscopically.

The macroscopic appearance includes sclerosis with thickening of the leaflets, calcification as irregular masses at the aortic side, thrombi, fractures and sometimes even bacterial vegetations [4^-7]. Calcification occurs at the bases of the cusps in the depth of the sinuses of Valsalva. This calcification extends throughout the leaflets as irregular nodules.

The microscopic description involves; 1) the endothelium, 2) the type and extent of calcification, 3) the collagen deposit, as well as the infiltration of 4) lipids and of 5) inflammatory cells.

2.1.. Endothelium

The endothelial cell line and its basement membrane are disrupted, even in mild forms of CAVS. The intima/media thickness has increased compared to normal individuals. This relates aortic sclerosis somehow to atheromatosis [5, 6, 8]. The degenerative lesions of CAVS are subendothelial with displacement of the elastic lamina. These lesions extend into the fibrosa [9]. The focal changes of sclerosis are located on the aortic side of the leaflets. This suggests that endothelial injury from low shear stress and high tensile stress are possible initiating factors in the disease process [10].

2.2.. Calcification

There is a wide spectrum of severity of CAVS: on the one end, there is sclerosis, which is more commonly observed in elderly, and which can be without clinical significance; on the other end there is a critical stenosis [9]. Calcification occurs at the base of the leaflets, in the sinuses of Valsalva and extends throughout the leaflets. Initially, these lesions can be seen as small foci consisting of calcium deficient hexagonal hydroxyl-apatite crystals. Osteopontin binds easily to these crystals [9]. At the end stage, masses of amorphous calcific nodule can be observed. Usually, the degree of calcification is correlated with the degree of valve stenosis [11].

2.3.. Collagen

An excess of collagen is produced in the spongiosa layer, as a response to mechanical stress [9]. The collagen is disorganized [5]. The fibrotic mass of the valve is negatively correlated with severity of stenosis [11].

2.4.. Lipid Infiltration

Large amounts of neutral lipids can be found inside and outside cells in CAVS. These lipids are not found in healthy valve leaflets. A strong association between serum lipids and CAVS has been documented. A proof of concept has been delivered by the observation that; 1) plant sterols accumulate in CAVS and 2) there is a relation to serum concentration. Lipids enter the leaflets and have their effects on the valvular interstitium [8].

2.5.. Cellular Infiltration

T-lymphocytes and macrophages are scarce in the normal aortic valve. From the onset of the development of CAVS, these cells are starting to accumulate. These inflammatory cells are found closely to the deposits of oxidized lipids. These cells secrete a number of cytokines, such as TNF. These substances initiate the expression of a number of ECM proteins and of enzymes, such as MMP. This could influence a remodeling process [5, 9, 12]. It is not certain that these inflammatory cells activate calcification.

3.. SIMILARITIES AND DIFFERENCES BETWEEN CAVS AND ATHEROMATOSIS

3.1.. Similarities

Early lesions of CAVS are similar to atheromatosis, with lipid infiltration, inflammation and calcification. Both diseases are a consequence of an active process, in which lipid infiltration and the toxic effects of oxidized cholesterol are involved. In both, the basement membrane is disrupted and inflammatory cells, such as macrophages and T-cells, as well as calcification can be demonstrated. Both conditions have a number of risk factors in common: ageing, hypertension, use of tobacco, diabetes mellitus and hypercholesterolemia [8^-11, 13^-17]. There are some variations in the significant factors found for both conditions [10].

Several mechanisms can act in concert in both conditions. Elevated serum cholesterol facilitates lipid deposition after any injury of the endothelium from any cause. Use of tobacco increases permeability of endothelium and can promote lipid oxidation [10]. Fu...

Table of contents

• Welcome
• Table of Contents
• Title
• BENTHAM SCIENCE PUBLISHERS LTD.
• FOREWORD
• PREFACE
• The Normal Aortic Valve
• Pathology of CAVS
• Prevention of the Progress of CAVS
• Imaging in CAVS
• Challenges for Imaging in CAVS
• Choice of A Valve Prosthesis
• Principles of Follow-Up After Aortic Valve Replacement
• Results Obtained by Follow-Up
• Aortic Valve Replacement in Patients Aged Over 80 Years
• Valve Prosthesis Patient Mismatch
• TAVI: Trans-Catheter Aortic Valve Implantation
• TEHV – Tissue Engineering of Heart Valves