Ann Thorac Surg 2001;71:S368-S370
© 2001 The Society of Thoracic Surgeons
Autografts, allografts, and biological valves in children
Electron beam tomography for cusp calcification in homograft versus freestyle xenografts
Giovanni Melina, MDa,
Michael B. Rubens, FRCRb,
Mohamed Amrani, FRCSa,
Asghar Khaghani, FRCSa,
Magdi H. Yacoub, FRCSa
a Department of Cardiothoracic Surgery, Royal Brompton and Harefield Hospital, London, England, United Kingdom
b Department of Radiology, Royal Brompton and Harefield Hospital, London, England, United Kingdom
Address reprint requests to Sir Magdi Yacoub, Royal Brompton & Harefield NHS Trust, Sydney St, London SW3 6NP, England
e-mail: m.yacoub{at}ic.ac.uk
Presented at the VIII International Symposium on Cardiac Bioprostheses, Cancun, Mexico, Nov 3–5, 2000.
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Abstract
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Background. We have previously shown, by means of electron beam tomography, the pattern of calcification of the aortic root wall of homografts and porcine xenografts after aortic root replacement. However, application of similar methods for cusp calcification raises specific problems that have not been addressed before.
Methods. A new method for localizing and quantifying calcification of the aortic valve cusps has been evolved. Intravenous contrast-enhanced electron beam tomography was introduced to visualize the aortic cusps. This technique was applied to quantify cusp calcification in 37 patients after aortic root replacement with a homograft (group H) or a Medtronic Freestyle valve (group F) at set intervals between 6 months and 2 years. A calcification score in Hounsfield units (HU) and a calcified volume score in cubic millimeters were calculated.
Results. The aortic leaflets were clearly visualized in all patients. The mean calcium score in the cusps was 28.8 ± 64.4 HU in group F and 62.4 ± 66.9 HU in group H (p = not significant). The mean calcified volume score was 327.0 ± 425.9 mm3 in group F and 642.0 ± 443.0 mm3 in group H (p = not significant).
Conclusions. Contrast enhancement electron beam tomography is a useful tool for quantification of calcium in the aortic valve leaflets. Our preliminary results show a tendency toward more calcification in the homografts. This needs to be studied further in a bigger cohort of patients followed up for longer periods.
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Introduction
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Calcification of biologic prostheses, particularly the cusps, is a major determinant of valve function. Using conventional echocardiographic and radiographic techniques, calcification of the aortic valve becomes evident only when a significant gradient across the valve develops. The approximate degree of calcification of the native aortic cusps as estimated by echocardiography is thought to be a predictor of prognosis in patients with asymptomatic aortic stenosis [1]. Electron beam tomography (EBT) has been widely used to detect calcium in the coronary arteries and aortic wall [2, 3]. We have previously shown the pattern of calcification of the aortic wall after homograft versus Freestyle (Medtronic Inc, Minneapolis, MN) root replacement by means of EBT using a new modified method [4]. Routine EBT does not localize the aortic valve leaflets because of the mobility of the leaflets and aortic ring during the different phases of the cardiac cycle. Accurate localization of the aortic cusps is essential for quantifying minor degrees of calcification with EBT. We aim to investigate aortic valve leaflets calcification using a contrast enhancement EBT in a group of patients undergoing aortic root replacement with a homograft or a Freestyle prosthesis from a prospective randomized trial.
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Material and methods
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Patients
Since August 1997, 137 patients with isolated aortic valve disease were randomly assigned to receive either a Medtronic Freestyle valve (group F; n = 76) or a homovital or antibiotic-sterilized (with or without cryopreservation) aortic homograft (group H; n = 61). Patients with severe heart failure or coronary artery disease were not excluded. Patients requiring other valve operations or presenting with active bacterial endocarditis were excluded. Informed consent was obtained from all patients. Table 1 shows the clinical characteristics of the study population
Surgical technique
Patients were cooled to 28°C under total cardiopulmonary bypass. Myocardial protection was achieved using antegrade cold blood cardioplegia infused through the aortic root or directly into the coronary ostia. The myocardial temperature was kept at less than 10°C. Cardioplegia infusions were repeated every 20 minutes. The left ventricle was vented through the left upper pulmonary vein or left ventricular apex.
All the valves (homograft and Freestyle) were inserted as an aortic root replacement with reimplantation of the coronary arteries. The aortic root replacement technique has been previously described [5, 6].
Electron beam tomography scans
Electron beam tomography scans of the aortic root were performed at 6 monthly intervals after valve replacement. A set of 20 transverse tomograms of 3-mm thickness was obtained through the aortic root with the subject performing a breath-hold. Acquisitions were made at 80% of the R-R interval. The scan was then repeated during intravenous injection of a contrast medium. Omnipaque 240 (Nycomed Imaging AS, Oslo, Norway) was injected into a vein in the antecubital fossa at a rate of 3 mL/s, and scans were acquired commencing 30 seconds after the beginning of the injection. The aortic valve leaflets were identified on the enhanced scan, and their location was then identified on the unenhanced scan. The aortic valve leaflet calcification was quantified using the method of Agatston and colleagues [2], which was originally developed for assessing coronary artery calcification and modified by us for measuring aortic wall calcification [4]. The calcification scoring method and the EBT definitions of the aortic root have been previously described [4].
Statistical analysis
Discrete variables were analyzed by means of the 
2 test, and Fisher’s exact test was used when necessary. Continuous variables were analyzed by means of the Student’s t test for unpaired data. A p value of 0.05 or less was considered statistically significant.
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Results
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Patient characteristics
Mean age was 64.6 ± 9.3 years in group H (range, 40 to 84 years) and 66.9 ± 6.7 years in group F (range, 48 to 78 years). Concomitant coronary artery bypass grafting was performed with root replacement in 13 patients (21.3%) of group H and in 21 patients (27.6%) of group F. Preoperative and operative data of the two groups are listed in Table 1.
Electron beam tomography results
Thirty-seven patients, 13 from group H and 24 from group F, underwent contrast enhancement EBT scans at different time intervals after the operation, giving a total of 60 scans. The homografts were obtained from donors aged 34 to 48 years, and the mean age of the recipients was 55.6 ± 4.8 years, which was not different from that of the Freestyle patients (58 ± 4.3 years). The aortic valve leaflets were clearly visible in all patients after the injection of the contrast medium (Fig 1). Minor degrees of calcification were detected already at 6 months after implantation in both groups, mainly at the commissures and possibly at the margins of the cusps. Table 2 shows the calcification scores for the two groups of patients. Although there was a trend towards more calcification in group H, this did not reach statistical significance.
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Fig 1. Electron beam tomography of the aortic root before (left) and after (right) intravenous contrast, showing the aortic valve leaflets.
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Comment
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This study describes a new method for detection and quantification of calcification in the aortic valve cusps by means of EBT.
Dystrophic calcification remains the main cause of stenotic or regurgitant failure in bioprosthetic heart valves in spite of the development of different anticalcification strategies [7], and this may affect valve performance and therefore several clinical end points including survival and quality of life [7–11]. Calcification is related to morphologic and biochemical changes, but the pathogenesis of this phenomenon is not completely understood. Physical forces to which the valve is exposed together with the recipient’s mineral metabolism may facilitate calcification [7, 10, 11]. The technique of root replacement is thought to maximize the benefit of unstented valve replacement [6, 12] as it preserves the geometric relation between all the component parts, which are essential for smooth valve function [13]. There is concern about the capacity of the aortic wall and leaflets of the root replacement to remain free of calcium, particularly in the xenograft tissue [8, 9].
We have recently reported the preliminary results of the use of EBT to determine calcification in the aortic root wall [4], but this method does not identify the aortic leaflets because of the mobility of the aortic valve and ring during the cardiac cycle. Minor degrees of calcification can only be detected after accurate localization of the aortic cusps. In this study we have used contrast enhancement to localize the aortic cusps. The detection and quantification of the calcium was then possible on the unenhanced scan.
As the degree of calcification of the native valve has been reported to be a determinant of prognosis or progression of the native aortic valve [1], this can be true for biologic valve prostheses. In addition the method described in this article can be used in the evaluation of patients before aortic valve replacement.
In this study calcification was found mainly at the commissural level and at the free margins of the cusps. An experimental study in sheep [14] showed similar results using radiologic and microscopic investigations that confirmed the presence of calcium at the cusp commissures after xenograft explantation. The present study addresses postoperative cusp calcification in patients.
In conclusion, contrast enhancement EBT provides a powerful tool by which the calcium in the aortic valve leaflets can be quantitated. The method needs to be validated further by comparing radiographic findings with calcification in the cusps determined by other techniques.
Our preliminary results show that minor degrees of calcification of the cusps start as early at 6 months after operation and that this calcification appears to be less in the Freestyle grafts as compared with homografts. This finding, however, needs to be confirmed in larger studies followed up for longer periods.
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References
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Abstract
Introduction
