Normal Human Valve Research Articles

First quantitative dosages: Strong correlations between non-5-HT2Rs serotonin receptors on normal human heart valves.

Although critical in animal and human development and pathology, a measurement of the quantitative expression of 5-HTR serotonin receptors on animal or human valvular tissues has never been performed. Quantification of the most frequent 5-HTRs reported as being present in human peripheral tissue was performed using radiolabeled agonists/antagonists. A membrane protein extract from normal human valves (aortic/mitral/tricuspid and some pulmonary) and associated diseased left myocardium, all unusable in clinics, were obtained from the Homograft bank. We analyzed 5-HT1AR/5-HT1B/DR/5-HT2AR/5-HT2BR/5-HT 2CR/5-HT4R/5-HT7R from 28 hearts. We confirmed the presence of tissue and measured the quantitative content for respective proteins in femtomol/mg of protein extracts: for 5-HT2AR (35.9+/-0.7), 5-HT2BR (28.8+/-1.3) but also a newly observed and robust expression for 5-HT4R (38+/-4.2). We identified one, 5-HT1ARs (4.9+/-0.3), and the possible expression, but at a very low level, of previously reported 5-HT1B/DRs (1.3+/-0.5) as well as the new 5-HT7Rs (3.5+/0.1) and 5-HT2CRs (1.2+/-0.1). Interestingly, by using univariate analysis, we were able to observe many correlations between the different 5-HTR levels of expression especially between 5-HT1AR/5-HT1B/DR and also between 5-HT4R/5-HT7R, but none were observed between 5-HT2AR and 5-HT2BR. Using multivariate analyses for a specific 5-HTR level of expression, after adjustment for implantation sites and other 5-HTRs, we found that 5-HT1AR was correlated with 5-HT1B/DR;5-HT4R with 5-HT7R and 5-HT1AR;5-HT2BR with 5-HT2AR only. For 5-HT2C, no correlation was observed. 5-HT2AR/5-HT2BR and 5-HT4R were all observed to have a high and equal level of expression on human valves, but that of 5-HT1AR was more limited. Since these non-5-HT2Rs are coupled with different G-proteins, with specific signaling, theoretically they may control the main 5-HT2R signaling (i.e., PLC/DAG-PKC-ERK/Ras/Src signaling) involved in valvular fibrosis and degeneration.

Patient Prosthesis Mismatch

AbstractConcept of patient prosthesis mismatch came into existence from 1978 onward when Rahimtoola first defined it as “mismatch can be considered to be present when the effective prosthetic valve area, after insertion into the patient, is less than that of a normal human valve.” Patient prosthesis mismatch produces higher than expected pressure gradient through normally functioning valve. Since insertion of first ball caged mechanical valve in descending aorta by Dr. Charles Hufnagel in 1952, prosthetic valve had undergone tremendous improvement in terms of valve design, hemodynamics, durability, and thrombogenicity. Despite these marked changes in valve design, prosthetic valves are still subjected to inherent complications.

Clinical and Technical Challenges of Prosthesis–Patient Mismatch After Transcatheter Aortic Valve Implantation

Prosthesis–patient mismatch (PPM) is present when the effective area of a prosthetic valve inserted into a patient is inferior to that of a normal human valve; the hemodynamic consequence of a valve too small compared with the size of the patient's body is the generation of higher than expected transprosthetic gradients. Despite evidence of increased risk of short- and long-term mortality and of structural valve degeneration in patients with PPM after surgical aortic valve replacement, its clinical impact in patients subject to transcatheter aortic valve implantation (TAVI) is yet unclear. We aim to review and update on the definition and incidence of PPM after TAVI, and its prognostic implications in the overall population and in higher-risk subgroups, such as small aortic annuli or valve-in-valve procedures. Last, we will focus on the armamentarium available in order to reduce risk of PPM when planning a TAVI procedure.

Abstract 385: Characterization of Cellular Infiltrate in Bioprosthetic Aortic and Mitral Valves

Background: Bioprosthetic xenogeneic valves tend to deteriorate over time, termed structural valve deterioration (SVD), leading to valvular dysfunction. Several studies have hypothesized that SVD is a result of a chronic immune-mediated rejection process; however, a paucity of data exists demonstrating this conclusively. Objectives: Demonstrate that valves explanted for SVD contain a significantly greater burden of immune cellular infiltrate compared to normal human heart valves. Methods: Adult patients undergoing bioprosthetic aortic or mitral valve explantation secondary to a diagnosis of SVD were included in this study. A control arm included valves explanted from hearts without valvular disease considered for transplantation that were not utilized. Specimens underwent immunohistochemical staining using standard techniques utilizing the following primary monoclonal antibodies: anti-CD68, anti-CD20, and anti-CD3. Results: Eighteen valves explanted for SVD were analyzed along with 4 control valves. All valves were explanted from male patients with a mean age of 62-years. Overall, 12% (n=1) of patients had diabetes mellitus, 50% (n=4) had hypertension, 12% (n=1) had renal dysfunction and 38% (n=3) were on a lipid-lowering medication. Our results demonstrate that valves developing SVD have a cellular infiltrate containing significantly more immune cells than normal human valves. Specifically, there are significantly more CD3+ T-cells (p<0.05) and CD68+ macrophages (p<0.05) present in the cellular infiltrate of the SVD valves compared to the normal controls. Furthermore, while the cellular infiltrate of the SVD valves contains CD20+ B-cells, plasma cells, and neutrophils, none of these cells are present on the normal control valves (all p-values <0.05). Conclusions: Our data suggest a significantly greater immune cell infiltrate can be found in explanted bioprosthetic valves developing SVD than normal human valves, providing support for the chronic-immune mediated rejection hypothesis. This study will ultimately lead to a better understanding of the immune mechanisms responsible for SVD in bioprosthetic xenograft valves and will contribute to our goal of developing novel therapeutic techniques to mitigate development of SVD.

A geometric model for the human pulmonary valve in its fully open case.

The human pulmonary valve, one of the key cardiac structures, plays an important role in circulatory system. However, there are few mathematical models to accurately simulate it. In this paper, we establish a geometric model of the normal human pulmonary valve from a mathematical perspective in the fully opening case. Based on the statistical data of the human pulmonary valves, we assume that the motions of the three cusps are symmetrical in the cardiac cycle. Thus, we first propose that each cusp is a part of the cylindrical shell according to its structure and physiological feature. The parameters for the pulmonary valve cusps in three-dimensional space are obtained by the fitting functions. We verify the accuracy of our results by comparing the areas of the pulmonary valve and pulmonary valve flap.

Aortic calcified particles modulate valvular endothelial and interstitial cells.

Normal and calcified human valve cusps, coronary arteries, and aortae harbor spherical calcium phosphate microparticles of identical composition and crystallinity, and their role remains unknown. The objective was to examine the direct effects of isolated calcified particles on human valvular cells. Calcified particles were isolated from healthy and diseased aortae, characterized, quantitated, and applied to valvular endothelial cells (VECs) and interstitial cells (VICs). Cell differentiation, viability, and proliferation were analyzed. Particles were heterogeneous, differing in size and shape, and were crystallized as calcium phosphate. Diseased donors had significantly more calcified particles compared to healthy donors (P<.05), but there were no differences between the composition of the particles from healthy and diseased donors. VECs treated with calcified particles showed a significant decrease in CD31 and VE-cadherin and an increase in von Willebrand factor expression, P<.05. There were significantly increased α-SMA and osteopontin in treated VICs (P<.05), significantly decreased VEC and VIC viability (P<.05), and significantly increased number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive VECs (P<.05) indicating apoptosis when treated with the calcified particles. Isolated calcified particles from human aortae are not innocent bystanders but induce a phenotypical and pathological change of VECs and VICs characteristic of activated and pathological cells. Therapy tailored to reduce these calcified particles should be investigated.

Valve Tissue Engineering with Living Absorbable Threads.

Tissue engineering (TE) depends on the population of scaffolds with appropriate cells, arranged in a specific physiological direction using a variety of techniques. Here, a novel technique of creating "living threads" is described based on thin (poly(ε-caprolactone) fibers of different diameters (23-243 μm). The fibers readily attract human mesenchymal stem cells (MSCs), which are firmly adhered. These versatile fibers can be used to produce dimensional shapes identical in shape to the cup-like structure of a normal human valve, while preserving the specific orientation of both the cells and the fibers. The MSCs on leaflets and the cells cultured in flask shown similar epitopes expression when analyzed by fluorescence activated cell sorting. Together, these characteristics have important functional implications as living absorbable fibers can be a valuable resource in TE of living tissues, including heart valves.

Activation of TLR3 induces osteogenic responses in human aortic valve interstitial cells through the NF-κB and ERK1/2 pathways.

Calcific aortic valve disease (CAVD) is characterized by chronic inflammation and progressive calcification in valve leaflets. Aortic valve interstitial cells (AVICs) play a critical role in the pathogenesis of CAVD. Previous studies show that stimulation of Toll-like receptor (TLR) 2 or TLR4 in AVICs in vitro up-regulates the expression of osteogenic mediators. Double-stranded RNA (dsRNA) can activate pro-inflammatory signaling through TLR3, the NLRP3 inflammasome and RIG-I-like receptors. The objective of this study is to determine the effect of dsRNA on AVIC osteogenic activities and the mechanism of its action. Methods and results: AVICs isolated from normal human valves were exposed to polyinosinic-polycytidylic acid [poly(I:C)], a mimic of dsRNA. Treatment with poly(I:C) increased the production of bone morphogenetic protein-2 (BMP-2), transforming growth factor beta-1 (TGF-β1) and alkaline phosphatase (ALP), and resulted in calcium deposit formation. Poly(I:C) induced the phosphorylation of NF-κB and ERK1/2. Knockdown of TLR3 essentially abrogated NF-κB and ERK1/2 phosphorylation, and markedly reduced the effect of poly(I:C) on the production of BMP-2, TGF-β1 and ALP. Further, inhibition of either NF-κB or ERK1/2 markedly reduced the levels of BMP-2, TGF-β1 and ALP in cells exposed to poly(I:C). Conclusion: Poly(I:C) up-regulates the production of BMP-2, TGF-β1 and ALP, and promotes calcium deposit formation in human AVICs. The pro-osteogenic effect of poly(I:C) is mediated primarily by TLR3 and the NF-κB and ERK1/2 pathways. These findings suggest that dsRNA, when present in aortic valve tissue, may promote CAVD progression through up-regulation of AVIC osteogenic activities.

Notch1 Promotes the Pro-Osteogenic Response of Human Aortic Valve Interstitial Cells via Modulation of ERK1/2 and Nuclear Factor-κB Activation

Calcific aortic valve disease is a leading cardiovascular disease in the elderly, and progressive calcification results in the failure of valvular function. Aortic valve interstitial cells (AVICs) from stenotic valves express higher levels of bone morphogenetic protein-2 in response to Toll-like receptor 4 stimulation. We recently found that Toll-like receptor 4 interacts with Notch1 in human AVICs. This study tests the hypothesis that Notch1 promotes the pro-osteogenic response of human AVICs. AVICs isolated from diseased human valves expressed higher levels of bone morphogenetic protein-2 and alkaline phosphatase after lipopolysaccharide stimulation. The augmented pro-osteogenic response is associated with elevated cellular levels of Notch1 and enhanced Notch1 cleavage in response to lipopolysaccharide stimulation. Inhibition or silencing of Notch1 suppressed the pro-osteogenic response in diseased cells, and the Notch 1 ligand, Jagged1, enhanced the response in AVICs isolated from normal human valves. Interestingly, extracellular signal-regulated protein kinases 1/2 (ERK1/2) and nuclear factor-κB phosphorylation induced by lipopolysaccharide was markedly reduced by inhibition or silencing of Notch1 and enhanced by Jagged1. Inhibition of ERK1/2 or nuclear factor-κB also reduced bone morphogenetic protein-2 and alkaline phosphatase expression induced by lipopolysaccharide. Notch1 mediates the pro-osteogenic response to Toll-like receptor 4 stimulation in human AVICs. Elevated Notch1 levels and enhanced Notch1 activation play a major role in augmentation of the pro-osteogenic response of AVICs of stenotic valves through modulation of ERK1/2 and nuclear factor-κB activation. These pathways could be potential therapeutic targets for prevention of the progression of calcific aortic valve disease.

Vascularity of human atrioventricular valves: A myth or fact?

Knowledge of heart valve vascularity is an important factor for understanding the valvular pathology and to develop tissue-engineered valves for repair procedures. Some investigators believe that blood vessels may exist in normal human heart valves whereas some recent publications have proposed that the presence of blood vessels in the valves is secondary to inflammation. Tissues from 60 normal formalin-fixed human hearts were examined microscopically for type, location, and number of vessels in atrioventricular valves. The age of the patient ranged from 10 to 70years, and an attempt was made to study the age-related morphologic changes in atrioventricular valves. Of the 60 tricuspid and 60 mitral valves examined, 12 tricuspid (20%) and 14 mitral (23.33%) valves were found to have vessels without the presence of an inflammatory process. In tricuspid valves the vessels were observed mainly in the fibrosa layer with a range of 1 to 4 vessels, whereas in mitral valves the vessels were situated mainly in the spongiosa layer with a range of 1 to 2 vessels. The maximum vascularity was seen in the fourth decade of life, in which the vessels were found in 40% of both tricuspid and mitral valves. The mean transverse diameter of these vessels was 0.23±0.18mm, with a range of 0.06 to 0.79mm in tricuspid valves, whereas it was 0.15±0.08mm, with a range of 0.04 to 0.4mm in mitral valves. The capillaries (3-11 capillaries) were found scattered in the fibrosa and spongiosa with an average lumen area of 0.39±0.18mm(2). The blood vessels in atrioventricular valves also can be seen in the absence of inflammation and are likely to be a necessary component of valve leaflets. Thus, when performing procedures involving in situ tissue engineering and valve repair the physician needs to be aware of the presence of these vessels in human heart valves.

Patient-prosthesis mismatch after transapical aortic valve implantation.

Patientprosthesis mismatch (PPM) was described by Rahimtoola in 1978 (1) as an effective prosthetic valve area that is less than that of a normal human valve. Despite technical efforts to optimize valve prostheses, their rheological properties are not comparable with those of native human valves and aortic stenosis will occur in a normally functioning prosthesis that is too small for the patient. PPM is associated with decreased regression of left ventricular hypertrophy, reduced coronary flow reserve, increased incidence of congestive heart failure, diminished functional capacity, and increased risk of early and late mortality (2,3). This paper is a brief review of the clinical significance of PPM, with reference to transcatether aortic valve implantation (TAVI).

Plastia tricúspide utilizando anuloplastia baseada na proporção entre os segmentos do anel da valva tricúspide normal

To determine the proportion between the segments of the normal human tricuspid valve (TV) annulus and its use as a parameter for ring annuloplasty "in vitro" and "in vivo". Digital images of the tricuspid ring of 30 human cadaveric hearts, without fixation and without tricuspid regurgitation (TR), were analyzed and the proportion between the antero-posterior and septal segments was determined. This proportion was used for TV annuloplasty with bovine pericardium (BP) flexible rings on 15 hearts from adult cadavers with TR and ring dilatation. The same proportion and technique were used for TV repair on 11 patients with functional TR. Preoperatively, seven patients had severe and four moderate TR; five patients were class IV and six class III (NYHA). The mean ratio between the antero-posterior and septal segments was 2.43+/-0.212 in the 30 hearts without TR. The mean size of the BP flexible ring used for "in vitro" surgical procedure was 71.5+/-5.2 mm, median 70 mm, and there was no TR after that in all 15 hearts. The mean size of the orthesis used on the patients was 73.4+/-6.5 mm, median 72 mm. There was 1 hospital death. Six months after surgery, 7 patients had no TR and 3 had mild TR; 6 patients were in NYHA class I, 3 in class II and 1 in class III. The use of the ratio 2.43:1 between the anterior-posterior and septal segments as a parameter in tricuspid valve annuloplasty with a bovine pericardium flexible ring leads to satisfactory results.

A Case of Prosthesis-Patient Mismatch Complicating Pregnancy

Prosthesis-patient mismatch occurs when the effective prosthetic valve area is smaller than that of a normal human valve. Its importance in pregnancy is unknown. We describe an asymptomatic patient with higher than normal transvalvular gradients due to prosthesis-patient mismatch who developed congestive heart failure in late pregnancy. Our recommendation is that pregnant patients, particularly those with a small valve prosthesis, undergo serial echocardiography because these patients are at high risk of developing heart failure.

Proporção entre os segmentos do anel da valva tricúspide normal: um parâmetro para realização da anuloplastia valvar

Objective: The purpose of this study was to determine the proportions among the segments of the human tricuspid valve annulus. Methods: A descriptive autopsy study was made of 30 human hearts without fixation, within six hours of death, without congenital or acquired lesions and without tricuspid regurgitation. Tricuspid valve insufficiency was excluded by the infusion of pressurized water in the right ventricle with the pulmonary valve closed. Digital images of the tricuspid ring in its anatomical position and after flattening were analyzed by specific software. The mean measurements and ratios were compared in the two different situations. Results: The mean measurements of the perimeter, septal and antero-posterior segments of the tricuspid ring in the anatomical position were: 105 mm (± 12.7), 30.6 mm (± 3.7) and 74 mm (± 9.4), respectively. When flattened, the mean measurement of the perimeter was 117.5 mm (± 13.3) and the sizes of the septal, anterior and posterior segments were 32 mm (± 3.7), 46.3 mm (± 8.3) and 39.1 mm (± 8.5), respectively. The mean ratio between the antero-posterior and septal segments was 2.43 (± 0.212) in the anatomical position and when flattened it was 2.67 (± 0.304). Statistical differences were observed in the measurements of the perimeter (p<0.0001), septal segment (p=0.003) and antero-posterior segment (p<0.0001) in both situations. Statistical differences also occurred in the ratios between the antero-posterior and septal segments (p=0.0005). Conclusions: The proportion between the septal and antero-posterior segments of the normal human tricuspid valve is 1:2.43. Flattening the tricuspid ring to measure the segments, changes the values and the ratios between them.

Calcified Rheumatic Valve Neoangiogenesis Is Associated With Vascular Endothelial Growth Factor Expression and Osteoblast-Like Bone Formation

Rheumatic heart disease is the most common cause of valvular disease in developing countries. Despite the high prevalence of this disease, the cellular mechanisms are not well known. We hypothesized that rheumatic valve calcification is associated with an osteoblast bone formation and neoangiogenesis. To test this hypothesis, we examined human rheumatic valves replaced at surgery (n=23), normal human valves (n=20) removed at cardiac transplantation, and degenerative mitral valve leaflets removed during surgical valve repair (n=15). Microcomputed tomography was used to assess mineralization fronts to reconstruct the extents of mineralization. Immunohistochemistry was used to localize osteopontin protein, alpha-actin, osteocalcin, vascular endothelial growth factor, von Willebrand factor, and CD68 (human macrophage). Microcomputed tomography demonstrated complex calcification developing within the heavily calcified rheumatic valves, not in the degenerative mitral valves and control valves. Immunohistochemistry localized osteopontin and osteocalcin to areas of smooth muscle cells within microvessels and proliferating myofibroblasts. Vascular endothelial growth factor was present in areas of inflammation and colocalized with the CD68 stain primarily in the calcified rheumatic valves. Alizarin red, osteopontin, and osteocalcin protein expression was upregulated in the calcified rheumatic valves and was present at low levels in the degenerative mitral valves. These findings support the concept that rheumatic valve calcification is not a random passive process but a regulated, inflammatory cellular process associated with the expression of osteoblast markers and neoangiogenesis.

Prosthesis-Patient Mismatch Predicts Short-Term Post-AVR Mortality

For most valve prostheses, the effective orifice area (EOA) does not reach that of a normal human valve, a phenomenon known as prosthesis-patient

Smoothelin-positive cells in human and porcine semilunar valves.

Our aim was to further characterize the interstitial cell phenotypes of normal porcine and human semilunar valves, information necessary for the design of bioengineered valves and for the understanding of valve disease processes such as aortic valve sclerosis. Existence of fibroblasts, myofibroblasts, and smooth muscle-like cells within semilunar heart valves has been established. However, the nature of the smooth muscle cell population has been controversial. We used immunochemical and western blotting methods to determine the status of smoothelin and smooth muscle alpha-actin in the valve. Our examination of valve interstitial cells confirmed the presence of terminally differentiated, contractile smooth muscle cells in situ. They were arranged in small bundles of 5-35 cells within the ventricularis or as individual cells scattered throughout the valvular layers in vivo, and were present in cells explanted from the valves in vitro. Colocalization of these proteins in semilunar heart valves was achieved with double-labeling experiments. Protein extraction, followed by coimmunoprecipitation, electrophoresis, and western blotting confirmed the immunochemical analysis and suggested that smooth muscle alpha-actin and smoothelin interact, as has been previously postulated. The presence of contractile smooth muscle within the valve may be an important factor in understanding valve pathology and in the design of tissue engineering efforts.

Human aortic valve calcification is associated with an osteoblast phenotype.

Calcific aortic stenosis is the third most common cardiovascular disease in the United States. We hypothesized that the mechanism for aortic valve calcification is similar to skeletal bone formation and that this process is mediated by an osteoblast-like phenotype. To test this hypothesis, we examined calcified human aortic valves replaced at surgery (n=22) and normal human valves (n=20) removed at time of cardiac transplantation. Contact microradiography and micro-computerized tomography were used to assess the 2-dimensional and 3-dimensional extent of mineralization. Mineralization borders were identified with von Kossa and Goldner's stains. Electron microscopy and energy-dispersive spectroscopy were performed for identification of bone ultrastructure and CaPO4 composition. To analyze for the osteoblast and bone markers, reverse transcriptase-polymerase chain reaction was performed on calcified versus normal human valves for osteopontin, bone sialoprotein, osteocalcin, alkaline phosphatase, and the osteoblast-specific transcription factor Cbfa1. Microradiography and micro-computerized tomography confirmed the presence of calcification in the valve. Special stains for hydroxyapatite and CaPO4 were positive in calcification margins. Electron microscopy identified mineralization, whereas energy-dispersive spectroscopy confirmed the presence of elemental CaPO4. Reverse transcriptase-polymerase chain reaction revealed increased mRNA levels of osteopontin, bone sialoprotein, osteocalcin, and Cbfa1 in the calcified valves. There was no change in alkaline phosphatase mRNA level but an increase in the protein expression in the diseased valves. These findings support the concept that aortic valve calcification is not a random degenerative process but an active regulated process associated with an osteoblast-like phenotype.

Mechanisms of aortic valve incompetence: Finite-element modeling of Marfan syndrome

Objectives: Progressive aortic root dilatation and an increased aortic root elastic modulus have been documented in persons with Marfan syndrome. To examine the effect of aortic root dilatation and increased elastic modulus on leaflet stress, strain, and coaptation, we used a finite-element model. Methods: The normal model incorporated the geometry, tissue thickness, and anisotropic elastic moduli of normal human roots and valves. Four Marfan models were evaluated, in which the diameter of the aortic root was dilated by 5%, 15%, 30%, and 50%. Aortic root elastic modulus in the 4 Marfan models was doubled. Under diastolic pressure, regional stresses and strains were evaluated, and the percentage of leaflet coaptation was calculated. Results: Root dilatation and stiffening significantly increased regional leaflet stress and strain compared with normal levels. Stress increases ranged from 80% to 360% and strain increases ranged from 60% to 200% in the 50% dilated Marfan model. Leaflet stresses and strains were disproportionately high at the attachment edge and coaptation area. Leaflet coaptation was decreased by approximately 20% in the 50% root dilatation model. Conclusions: Increasing root dilatation and root elastic modulus to simulate Marfan syndrome significantly increases leaflet stress and strain and reduces coaptation in an otherwise normal aortic valve. These alterations may influence the decision to use valve-sparing aortic root replacement procedures in patients with Marfan syndrome.J Thorac Cardiovasc Surg 2001;122:946-54

Mechanisms of aortic valve incompetence: finite element modeling of aortic root dilatation

Background. Idiopathic root dilatation often results in dysfunction of an otherwise normal aortic valve. To examine the effect of root dilatation on leaflet stress, strain, and coaptation, we utilized a finite element model. Methods. The normal model incorporated the geometry, tissue thickness, stiffness, and collagen fiber alignment of normal human roots and valves. We evaluated four dilatation models in which diameters of the aortic root were dilated by 5%, 15%, 30%, and 50%. Regional stress and strain were evaluated and leaflet coaptation percent was calculated under diastolic pressure. Results. Root dilatation significantly increased regional leaflet stress and strain beyond that found in the normal model. Stress increases ranged from 57% to 399% and strain increases ranged from 39% to 189% in the 50% dilatation model. Leaflet stress and strain were disproportionately high at the attachment edge and coaptation area. Leaflet coaptation was decreased by 18% in the 50% root dilatation model. Conclusions. Idiopathic root dilatation significantly increases leaflet stress and strain and reduces coaptation in an otherwise normal aortic valve. These alterations may affect valve-sparing aortic root replacement procedures.