Calcification Of Bioprosthetic Valves Research Articles

Multiscale multimodal characterization and simulation of structural alterations in failed bioprosthetic heart valves.

Calcific degeneration is the most frequent type of heart valve failure, with rising incidence due to the ageing population. The gold standard treatment to date is valve replacement. Unfortunately, calcification oftentimes re-occurs in bioprosthetic substitutes, with the governing processes remaining poorly understood. Here, we present a multiscale, multimodal analysis of disturbances and extensive mineralisation of the collagen network in failed bioprosthetic bovine pericardium valve explants with full histoanatomical context. In addition to highly abundant mineralized collagen fibres and fibrils, calcified micron-sized particles previously discovered in native valves were also prevalent on the aortic as well as the ventricular surface of bioprosthetic valves. The two mineral types (fibres and particles) were detectable even in early-stage mineralisation, prior to any macroscopic calcification. Based on multiscale multimodal characterisation and high-fidelity simulations, we demonstrate that mineral occurrence coincides with regions exposed to high haemodynamic and biomechanical indicators. These insights obtained by multiscale analysis of failed bioprosthetic valves serve as groundwork for the evidence-based development of more durable alternatives. STATEMENT OF SIGNIFICANCE: Bioprosthetic valve calcification is a well-known clinically significant phenomenon, leading to valve failure. The nanoanalytical characterisation of bioprosthetic valves gives insights into the highly abundant, extensive calcification and disorganization of the collagen network and the presence of calcium phosphate particles previously reported in native cardiovascular tissues. While the collagen matrix mineralisation can be primarily attributed to a combination of chemical and mechanical alterations, the calcified particles are likely of host cellular origin. This work presents a straightforward route to mineral identification and characterization at high resolution and sensitivity, and with full histoanatomical context and correlation to hemodynamic and biomechanical indicators, hence providing design cues for improved bioprosthetic valve alternatives.

Valve-in-valve transcatheter aortic valve replacement on a self-expandable nitinol frame due to degeneration of primary bioprosthetic valve cusps. Clinical case of a high-risk surgical female patient

Introduction. We present the clinical observation of a 72-year-old female patient with high surgical risk and structural degeneration of a bioprosthetic aortic valve (AV) cusps in the form of stenosis, accompanied by severe dysfunction. Transcatheter implantation of bioprosthesis Medtronic CoreValve™ Evolut™ R-23 was performed using the valve-in-valve technique. The choice of minimally invasive treatment tactics is substantiated, a preoperative examination algorithm and a specific bioprosthesis model for such intervention are provided. Materials and methods. Imaging – echocardiography (Echo), electrocardiography, multispiral computed tomography, coronary angiography. Bioprosthetic valve calcification and stenosis with critical parameters of the bioprosthetic AV peak pressure gradient according to Echo data were the indications for minimally invasive surgery. Results. Dynamic observation revealed a progressive deterioration in the function of the previously implanted bioprosthetic heart valve in the aortic position, and a critical deterioration in the patient’s condition. After additional examination of the patient and selection of a new prosthesis, valve-in-valve transcatheter aortic valve replacement was done. The positive dynamics of the general state of the patient was noted in the early postoperative period. Echo data showed that the bioprosthetic AV peak systolic pressure gradient decreased from 90 to 29 mmHg, average gradient – from 42 to 19 mmHg. Conclusion. The minimally invasive valve-in-valve transcatheter aortic valve replacement used to correct the dysfunction of a bioprosthetic AV that was previously implanted during an open surgery was shown to be safe and effective and can be considered as one of the options for repeat valve replacement.

Decellularization as a method to reduce calcification in bovine pericardium bioprosthetic valves.

Decellularization is an alternative method for processing biological tissues with decreased antigenicity and resistance to calcification. The aim of this study was to characterize the properties of decellularized (dCell) bovine pericardium fixed with 0.1% glutaraldehyde (GA) and to evaluate outcomes of bioprosthetic valves constructed with this tissue when implanted in the mitral position of juvenile sheep. Bioprosthetic mitral valves were constructed with fresh bovine pericardium fixed in 0.5% GA (control group) or dCell bovine pericardium fixed in 0.1% GA (study group). Before implantation, samples were submitted to histological (haematoxylin-eosin, Movat and 4',6-diamidino-2-phenylindole), biochemical (residual deoxyribonucleic acid and α-gal epitopes) and biomechanical characterization. Valves were implanted (n = 8 in each group) as a mitral valve replacement for 180 days in sheep and explants were re-evaluated histologically and for calcification with radiological studies and calcium content determination. Unimplanted dCell pericardia exhibited a well-preserved extracellular matrix with absence of cells, a 77% reduction in deoxyribonucleic acid levels and with no detectable α-gal epitopes. When compared to controls, they had lower ultimate tensile strength (7.3 ± 5.4 vs 10.2 ± 3.0 mPa, P = 0.04) and greater percentage elongation in the longitudinal direction (29 ± 6.5% vs 23.8 ± 5.1%, P = 0.02). After 180 days in mitral position, dCell valves showed pliable leaflets without macroscopic signs of calcification. Histologically, dCell leaflets had intact collagen fibres, better tissue remodelling and a significant 89% reduction in calcium content. This study demonstrates that bioprosthetic valves constructed with dCell bovine pericardium fixed in low GA concentration were resistant to calcification and may thereby improve long-term durability of the tissue.

Calcification and Thrombosis as Mediators of Bioprosthetic Valve Deterioration

Calcific aortic valve disease is the most common indication for surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) of diseased valves worldwide. 1 For years,...

Calcitonin as an anticalcification treatment for implantable biological tissues

Background and aim of the studyCalcification remains the major role of failure of implantable biomedical material and in particular of bioprosthetic valves. Various treatments have been proposed to mitigate calcification of glutaraldehyde-fixed bioprosthetic valves but none have succeeded in inhibiting or mitigating efficiently the calcification process of the implantable biological tissues. Since the discovery of calcitonin (CT) and its therapeutic role in treating hypercalcemic patients, CT has never been tried as an anticalcification treatment for biomaterials. It is postulated, that tissue calcification may be efficiently minimized by forming adducts with aldehyde groups thus eliminating the places of the biological tissues onto the calcium cations could be deposited. Material and methodsFresh porcine aortic leaflets were cut radially in three parts. Three groups of tissue were created. Group I (glutaraldehyde only), Group II (glutaraldehyde with 1% CT) and Group III (glutaraldehyde with 10% CT). All tissues were then implanted subdermally in three sets of 8 (Group I) and 9 (Group II and Group III) male Wistar rats of 12 days old. 21 days later the rats were euthanized by inhalation of CO2. The tissues were retrieved and after rinsing with distilled water 3 times, were lyophilized at −40°C at high vacuum pressure of approximately 100mmHg for 16h. The calcium content was then measured with flat atomic absorption technique. ResultsThe preimplantation values of Ca concentration as expressed in mg Ca/g of tissue were 1.79±0.14 in Group I, 4.78±0.0079 in Group II and 2.88±0.17 in Group III (p=ns). 21 days later the values of Ca concentration were 126.95±12.97 for Group I, 24.69±2.71 for Group II (p<0.05) and 27.16±2.95 for Group III (p<0.05). There was not significance difference between Groups II and III, even if Group II showed a less accumulation of Ca concentration (×5.16) than Group III (×9.43). ConclusionAn anticalcification treatment based on calcitonin as an additive to buffered glutaraldehyde, mitigates the calcification process of the implantable biological tissues, as compared to glutaraldehyde treatment only.

Relationship Between Calcium-phosphorous Product, Native and Bioprosthetic Mitral Valve Calcifications

Calcification is a common cause of failure of natural and bioprosthetic valves (BPV). Prior research on patients with chronic kidney disease identified increased calcium-phosphorus (Ca-P) product as a risk factor for both arterial and valvular calcifications, an aspect not thoroughly investigated in general population. The aims of our study were to analyse the functional impact of native and bioprosthetic mitral valve (MV) calcification detected on cardiac computed tomography angiography (CCTA), to evaluate risk factors and to assess potential differences from a morphological and chemical point of view between BPV and native MV calcification. The authors performed a retrospective study on 270 patients who underwent CCTA for suspected coronary artery disease, 225 patients with no history of MV replacement and 45 patients with bioprosthetic MV. Mitral leaflet calcification (MLC) was registered in 21 (9.33%) and mitral annular calcification (MAC) in 27 (12%) of the 225 patients suspected for CVD. Echocardiography identified MV sclerosis in 20 cases (8.89%) and MV stenosis in 12 cases (5.33%) with MLC and/or MAC. In the BPV group, 13 patients (28.89%) presented visible BPV calcification associated to echocardiographic regurgitation in 3 (30.77%) cases and higher mean transvalvular gradients. Increased Ca-P product and diabetes mellitus proved to be risk factors for both native and BPV calcification and time since surgery only for BPV calcification. Native and BPV calcification are associated to valve dysfunction and share structural characteristics, thus indicating similar calcification mechanisms. Good glycaemic control in diabetic patients and careful administration of bisphosphonates, calcium and vitamin D supplements are mandatory especially in patients with BPV in order to prevent valve dysfunction due to calcification.

Surgical pathology analysis of the causes of failure of 48 bioprosthetic heart valves in 40 Chinese cases

To investigate the pathological changes and related factors leading to failure of bioprosthetic valves. The surgical explanted bioprosthetic valves in Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 2006 to December 2014 were retrospectively reviewed. Calcification, cusp tears, pannus and infectious endocarditis of bioprosthetic valves were evaluated by gross examination, X ray photography and histopathological analysis. Meanwhile, the age and the site at implantation, and the tissue type of bioprosthetic valves, the implantation duration were obtained by chart review and used to be analyzed with the modes of valve failure. U test, χ(2) test and Fisher exact test were used to analyze the data. Total 48 bioprosthetic valves were collected from 40 cases with 26 females. Their age at the time of implantation was 12 to 71 years (median 58 years). The tissue types of bioprosthesis included 24 bovine pericardial valves and 24 porcine aortic valves respectively. The implantation sites included mitral in 29 valves, aortic in 14 valves and tricuspid in 5 valves. The implantation duration ranged from 5 days to 27 years (mean (111±77) months). The study showed that the commonest mode of valve failure was structural valve deterioration (32 valves, 66.7%). The fewer modes of valve failure were infectious endocarditis (9 valves, 18.7%) and non-structural valve deterioration (7 valves, 14.6%). No thrombosis was found in this series. The degree of calcification was correlated positively with implantation duration (r=0.52, P=0.000). The implantation duration of bovine pericardial valves was longer than that of porcine aortic valves ((146±74) months vs. (77±68) months, Z=-3.24, P=0.001). Porcine aortic valves had a higher incidence of cusp tears than bovine pericardial valves (66.7% vs. 16.7%, χ(2)=12.34, P=0.000) despite they had a relatively lower incidence of calcification (41.7% vs. 75.0%, χ(2)=5.37, P=0.019). For the age at the time of implantation, the patients ≤60 years old had more calcification of bioprosthetic valves compared with those >60 years old (45.1% vs. 2/17, χ(2)=5.51, P=0.019) whereas the patients ≤60 years old had fewer cusp tears (12.9% vs. 58.8%, P=0.002). Infectious endocarditis was found more frequently in the valves failure within 5 years than those failure after 5 years (6/14 vs. 8.8%, P=0.006). Structural valve deterioration is the principle cause of bioprosthetic valve failure while infectious endocarditis mainly involves the valves failure in early and middle terms after surgery. The mode of valve failure in the patients ≤60 years old is different from that in the patients >60 years old at the time of implantation. More calcification would occur in bioprosthetic valve in the younger patients.

A Genomics-Based Model for Prediction of Severe Bioprosthetic Mitral Valve Calcification.

Severe bioprosthetic mitral valve calcification is a significant problem in cardiovascular surgery. Unfortunately, clinical markers did not demonstrate efficacy in prediction of severe bioprosthetic mitral valve calcification. Here, we examined whether a genomics-based approach is efficient in predicting the risk of severe bioprosthetic mitral valve calcification. A total of 124 consecutive Russian patients who underwent mitral valve replacement surgery were recruited. We investigated the associations of the inherited variation in innate immunity, lipid metabolism and calcium metabolism genes with severe bioprosthetic mitral valve calcification. Genotyping was conducted utilizing the TaqMan assay. Eight gene polymorphisms were significantly associated with severe bioprosthetic mitral valve calcification and were therefore included into stepwise logistic regression which identified male gender, the T/T genotype of the rs3775073 polymorphism within the TLR6 gene, the C/T genotype of the rs2229238 polymorphism within the IL6R gene, and the A/A genotype of the rs10455872 polymorphism within the LPA gene as independent predictors of severe bioprosthetic mitral valve calcification. The developed genomics-based model had fair predictive value with area under the receiver operating characteristic (ROC) curve of 0.73. In conclusion, our genomics-based approach is efficient for the prediction of severe bioprosthetic mitral valve calcification.

Determinants of aortic bioprosthetic valve calcification assessed by multidetector CT

BackgroundCusp calcification is the main mechanism leading to bioprosthetic heart valve (BPV) failure. Recent studies suggest that BPV calcification is an active rather than passive process probably modulated by several...

Do Calcium supplements influence bioprosthetic valve calcification? Results of a prospective study on bioprosthetic valve calcification assessed by computed tomography

Background: Bioprosthetic valves (BPVs) are specifically recommended in patients older than 65 years because of their limited durability mainly due to progressive leaflet calcification with a reoperation rate for structural degeneration of 30% at 15 years. Recent data highlight that BPV calcification is an active rather than passive process probably modulated by several mechanisms including dysfunctional calcium-related metabolism. The objective of this prospective study was to identify the clinical and metabolic determinants of bioprosthetic calcification assessed by multi-detector computed tomography (CT). Methods and results: One hundred and ninety-four (194) consecutive patients (pts) with an aortic BPV were recruited and underwent a CT for BPV calcification assessment. A calcification score was individually calculated using the volumetric method and expressed in mm3. Patients also underwent a clinical evaluation with a detailed record of medications, a Doppler-echocardiographic exam and a complete plasma phospho-calcic profile. Forty-six (46) pts (24%) had a calcification score above zero mm3 and represented the BPV calcification group. Patients with BPV calcification had higher plasma levels of calcium (2.37±0.01mmol/l vs. 2.34±0.07mmol/l, p=0.1), higher plasma levels of phosphorus (1.06±0.15mmol/l vs. 1.02±0.15 mmol/l, p=0.1) and a significant higher calcium phosphorus product (2.55±0.36 mmol2/l2 vs. 2.41±0.39 mmol2/l2, p=0.04). On multivariate analysis, increased calcium phosphorus product (Odds ratio [OR]=1.11, 95% confidence interval [CI]: 1.01-1.23 p=0.02) and the presence of patient-prosthesis mismatch (OR=3.67, 95% CI: 1.25-10.6 p=0.01) were the strongest independent predictors of BPV calcification. Calcium supplement intake, age and female gender were independently associated with increased calcium phosphorus product. Conclusion: This study demonstrates a strong independent association between higher calcium phosphorus product and increased risk of BPV calcification assessed by CT. Furthermore, this study reports that calcium supplements which are extensively prescribed in elderly patients are independently associated with higher calcium phosphorus product. The influence of calcium supplementation on bioprosthetic valve calcification needs further studies to be clearly investigated because it may have important therapeutic implications.

Animal models for bench to bedside translation of regenerative cardiac constructs

Investigators seeking to select an animal model for use in preclinical research studies prior to FDA submission for allograft heart valves have several types to choose from. Dogs, pigs, cattle, primates and sheep have all served as successful medium and large animal models, and their murine counterparts have also been integral in the advancement of replacement heart valve research. While the national and international regulatory bodies have not specified a universal animal model for use in preclinical research studies, the ovine and porcine models have become the frontrunners within the peer-reviewed literature. Sheep are an excellent model of bioprosthetic valve calcification, with a robust mineralization response that mimics observations of human clinical disease progression, while swine are the model of choice for valves which pose a risk of thrombotic events. In the rapidly advancing field of tissue engineered cardiovascular products, dogs, primates, rodents, sheep and pigs are all valuable models for the study of scaffold remodeling and recellularization. Once an animal model has been chosen, investigators are recommended to consult with the FDA via submission of a Request for Designation in order to identify the type of product and the appropriate Center to which the product should be submitted. Additionally, the investigator should outline a risk analysis plan that categorizes the failure modes of the product, as well as design an in vivo pre-clinical safety and performance study that will capture data applicable to the assessment of the failure modes enumerated in the risk analysis.

Systemic lupus erythrematosus; its implication in cardiac surgery: Institutional case report

Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease that primarily affects young women. According to the literature, the prevalence of cardiovascular involvement in patients with systemic lupus erythematosus (SLE) has been estimated to be more than 50%. Valvular involvement is the most frequent cardiac manifestation in SLE. Functionally, valvular regurgitation hasbeen reported to occur in up to 74% of patients. Meanwhile valvular endocarditis is a frequent manifestation of SLE, and the mitral valve is most frequently affected. However, any valve or multivalvular affection may occur. Valvular lesions resulting from lupus can cause severe mitral regurgitation (MR). The most classic cardiac valvular abnormality in patientswith SLE is known as Libman–Sacks endocarditis, which consists of noninfective, verrucousvegetations(marantic endocarditis). They occur most frequently onthe mitral valve. Most of the valves that have vegetations are usually associated with diffuse thickeningor regurgitation. However, although cardiac involvement in patients with SLE has been recognized since the early 20th, But cardiac surgery was infrequently performed in patients with SLE, and its clinical outcome was reported only in small series. Also the impact of SLE on provision of anesthesia has never beeninvestigated, and the lack of evidence combined with theheterogeneity of disease manifestations makes it difficult toestablish definitive management protocols. That’s why, We herein describe a 22 years old female patient with SLE,with end stage renal diseaserequiring peritoneal dialysis. presented to our hospital (Al-Demerdash, Ain Shams University Hospital), with signsof congestiveheart failure such as dyspnea on exertion andorthopnea, paroxysmal nocturnal dyspnea, and fatigue, refractory to medical management.Her therapy for SLE required longterm prednisolonand hydroxychloroquine. Physical examination revealed no facial malar rash or generalized discoid rashes. The breath sounds were diminished at the lower lung zones. Cardiac auscultation showed regular heart beat with a heart rate of 102 beats/min, a grade III/VI systolic murmur at the left lower sternal border and the apex, and a pericardial friction rub. Palpation of the abdomen showed hepatomegaly. The extremities were notable for mild pitting edema. There was no clubbing, cyanosis or deformity of joints. Preoperative data Complete blood count revealed Hg 9.9 g/dl, WBC 11.100/ul, Platelet 247,000/ul. Bleeding Profile showed PT 16.4 sec, INR 1.45, PTT 44 sec. biochemistry work-up showed, Glucose 75 mg/dl, Creat 2.9 mg/dl with hemodialysis session, ALT 15U/l, AST 20U/l. Preoperative transesophageal Echocardiography showed: A large mass is attached to the atrial surface of the anterior mitral leaflet measuring 6 × 7 mm. the mass perforates the leaflet causing severe mitral regurgitation. And, another large mass measuring 6 × 9 mm attached to the non-coronary aortic valve cusp with 2 small masses attached to each of the other two leaflets causing severe aortic regurgitation.EF 60%,RVSP 50 mmHg. So the patient was scheduled for double valve replacement. Although valve repair and bioprosthetic valve replacement are not the best solution, since accelerated native valve and bioprosthetic valve calcification tend to occur because of the high calcium turnover. Also Porcine valves have become affected by valvulitiswith perforation of valve cusps. But, our cardiac surgical team decided to replace mitral and aortic valve with bioprothetic valve, as they believe that Anticoagulation may present higher risks in our young patient who require prolonged steroid use and who have end stage renal failure, the resultant dependence on dialysis. Also previous reports described patients with SLE who underwent mitral valve replacement, had a number of complications, and died secondary to anticoagulation. Also, because ofsuccessful placement of the porcine Carpentier-Edwards bioprosthesis in patients with SLE has been reported before. Finally weaning from cardiopulmonary bypass was uneventful (adrenaline 50 n/kg/min). The patient’s recovery from surgery was uncomplicated, and she was discharged on the 6th postoperative day. In conclusion, although the postoperative complication is common, cardiac operation could be performed in patients with SLE.

Early Postoperative Bioprosthetic Valve Calcification

Bioprosthetic valves are implanted in elderly patients with good follow up results. The degeneration of these valves is slow and there are multiple aetiologies for that. It is unclear whether renal failure accelerates the degeneration of bioprosthetic valves in patients with normal calcium levels. We present a case with tissue valve degeneration 16 months postoperatively in a patient with renal failure.

Early bioprosthetic valve calcification with alfacalcidol supplementation

We report a case of early bioprosthetic valve calcification in a 76 year-old woman who had received supplementation with alfacalcidol, an analogue of vitamin D, for 3 years after her initial valve replacement. She underwent aortic valve replacement at the age of 71 and subsequently complained of shortness of breath. Ultrasonic cardiography revealed severe aortic stenosis and we performed a second aortic valve replacement with a bioprosthesis. Histopathologic and x-ray examination showed calcification on the explanted valve. She had not presented with any known risk for early bioprosthetic calcification, suggesting that vitamin D supplementation may accelerate calcification of bioprosthetic valves.

Do statins slow the process of calcification of aortic tissue valves?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether statins slow the process of calcification of aortic tissue valves. Altogether 207 papers were found using the reported search, of which eight represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We acknowledge the limited evidence in this very specific field of cardiac surgery. Due to their pleiotropic effects, including anti-inflammatory properties, there has been speculation that statins could reduce and delay the degeneration and calcification of aortic bioprosthetic valves. Mainly, it was extrapolation of the recently discovered molecular similarities between atherosclerosis and native aortic valve stenosis (AS), with some evidence that statins may slow the progression of native aortic valve calcific degeneration, and the potential harmful impact of atherosclerotic risk factors on the development of native AS. Several studies have been conducted to evaluate the impact of hyperlipidemia and serum cholesterol levels on structural valve deterioration (SVD). Indeed, two studies suggested hyperlipidemia was a risk factor for SVD and correlated reoperation, from which one case-control study based on first-generation biological valves without specific anti-calcification treatment, while three - more convincing by number of patients observed and design of the study - reported contrary results. The other three studies focused on statin treatment in patients after aortic biological valve replacement. Two studies confirmed beneficial effects of statin therapy on valve hemodynamics or inflammatory damage in vivo, but another study, with significantly greater patients series, found lipid-lowering therapy futile in this clinical aspect. Currently, studies and their results are discordant, but statin therapy appears insufficient to result in better clinical outcomes. We conclude that even though the data is conflicting, statin therapy does not prevent SVD of bioprosthetic valves in the aortic position.

EComment: Factors related to bioprosthetic valve calcification in the elderly

eComment: Factors related to bioprosthetic valve calcification in the elderly

Neomycin fixation followed by ethanol pretreatment leads to reduced buckling and inhibition of calcification in bioprosthetic valves

Glutaraldehyde crosslinked bioprosthetic heart valves (BHVs) have two modalities of failure: degeneration (cuspal tear due to matrix failure) and calcification. They can occur independently as well as one can lead to the other causing co-existence. Calcific failure has been extensively studied before and several anti-calcification treatments have been developed; however, little research is directed to understand mechanisms of valvular degeneration. One of the shortcomings of glutaraldehyde fixation is its inability to stabilize all extracellular matrix components in the tissue. Previous studies from our lab have demonstrated that neomycin could be used as a fixative to stabilize glycosaminoglycans (GAGs) present in the valve to improve matrix properties. But neomycin fixation did not prevent cuspal calcification. In the present study, we wanted to enhance the anti-calcification potential of neomycin fixed valves by pre-treating with ethanol or removing the free aldehydes by sodium borohydride treatment. Ethanol treatment has been previously used and found to have excellent anti-calcification properties for valve cusps. Results demonstrated in this study suggest that neomycin followed by ethanol treatment effectively preserves GAGs both in vitro as well as in vivo after subdermal implantation in rats. In vivo calcification was inhibited in neomycin fixed cusps pretreated with ethanol compared to glutaraldehyde (GLUT) control. Sodium borohydride treatment by itself did not inhibit calcification nor stabilized GAGs against enzymatic degradation. Neomycin fixation followed by ethanol treatment of BHVs could prevent both modalities of failure, thereby increasing the effective durability and lifetime of these bioprostheses several fold.

Hypercholesterolemia is a risk factor for bioprosthetic valve calcification and explantation

Abstract Objective There are pathophysiologic similarities between calcification and atherosclerosis. We wished to determine whether risk factors for atherosclerosis were linked to bioprosthetic valve calcification and dysfunction. Methods We performed a retrospective cohort study on 144 patients at a single institution who had bioprosthetic aortic or mitral valves removed, serum cholesterol levels recorded, and valve calcification assessed on the basis of hematoxylin and eosin staining and radiography of the valve. We also performed case-control analysis of a group of 66 patients whose tissue valves were explanted and compared them with an age- and position-matched group of 66 patients with similar duration of implantation. We also compared mean serum cholesterol levels. Results In the retrospective cohort study cholesterol ( P = .035), younger age at implantation ( P = .014), and coronary artery disease ( P = .017) were linked to calcification of the valve by means of univariate analysis. In stepwise multiple regression analysis only the mean serum cholesterol level was linked to calcification ( P = .02). Sex, hypertension, smoking, diabetes, and implant position were not linked to calcification. In the case-control analysis the mean serum cholesterol level of the explanted valve group was significantly higher (189 vs 163 mg/dL, P Conclusions Increased serum cholesterol level may be a risk factor for bioprosthetic valve calcification requiring explantation.

Hypercholesterolemia is a risk factor for bioprosthetic valve calcification and explantation

Objective There are pathophysiologic similarities between calcification and atherosclerosis. We wished to determine whether risk factors for atherosclerosis were linked to bioprosthetic valve calcification and dysfunction. Methods We performed a retrospective cohort study on 144 patients at a single institution who had bioprosthetic aortic or mitral valves removed, serum cholesterol levels recorded, and valve calcification assessed on the basis of hematoxylin and eosin staining and radiography of the valve. We also performed case-control analysis of a group of 66 patients whose tissue valves were explanted and compared them with an age- and position-matched group of 66 patients with similar duration of implantation. We also compared mean serum cholesterol levels. Results In the retrospective cohort study cholesterol ( P = .035), younger age at implantation ( P = .014), and coronary artery disease ( P = .017) were linked to calcification of the valve by means of univariate analysis. In stepwise multiple regression analysis only the mean serum cholesterol level was linked to calcification ( P = .02). Sex, hypertension, smoking, diabetes, and implant position were not linked to calcification. In the case-control analysis the mean serum cholesterol level of the explanted valve group was significantly higher (189 vs 163 mg/dL, P < .0001) than that of the group whose valves did not require explantation. For those whose serum cholesterol levels were greater than 200 mg/dL, the odds ratio was 3.9 (95% confidence interval, 1.7-8.9) for valve explantation. Conclusions Increased serum cholesterol level may be a risk factor for bioprosthetic valve calcification requiring explantation.

Cholesterol in Vascular and Valvular Calcification

In the early 1990s, the late Jeff Hoeg had the foresight to ask whether vascular calcification relates to the duration and severity of exposure to cholesterol. In a group of homozygous hyperlipidemic patients for whom detailed records of cholesterol levels were available over a long period of time, he and his colleagues found that coronary calcification scores by ultrafast computed tomographic scanning correlated significantly with the cholesterol year product.1 Studies that lack long-term cholesterol history may miss a correlation between lipids and calcification, because current treatments so dramatically change cholesterol levels as to make them unrepresentative of long-term exposure. See p 1927 In the present issue of Circulation , Pohle et al2 successfully overcame these difficulties by studying the rate of change in calcification as a function of change in lipid levels, excluding patients in whom treatment was altered during the study period. These investigators found that both coronary calcification and aortic valve calcification progress more rapidly in subjects with levels of LDL >130 mg/dL. This finding dovetails with those of Callister et al,3 who discovered that patients who successfully lowered their cholesterol levels with lipid-lowering agents significantly reduced the progression of coronary calcification. In a large population of young subjects, the risk factor that correlated most significantly with coronary calcification was LDL cholesterol.4 This relation was stronger than the correlation with age, smoking, fasting insulin, blood pressure, or male sex.4 In another study of asymptomatic outpatients, LDL cholesterol was the only risk factor correlating with progression of coronary calcification by electron-beam computed tomography over an 18-month period.5 The correlation of LDL cholesterol exposure to valvular and vascular calcification raises the possibility of a mechanistic role, which is also supported by in vitro studies. Two groups …