Warfarin and aortic valve calcification in hemodialysis patients

BACKGROUND: This retrospective cohort study was designed to determine the association between long-term exposure to warfarin and severity of aortic valve (AV) calcification in hemodialysis (HD) patients. METHODS: One hundred and eight HD patients underwent a study-specific echocardiogram. A grading scheme was used to classify AV calcification as none, mild, moderate and severe. Demographic, biochemical and medication data were abstracted by chart review. RESULTS: One hundred and eight subjects were enrolled. A minority had no calcification (n=17, 15.7%), the majority had mild calcification (n=62, 57.4%), and fewer had calcification rated as moderate (n=16, 14.8%) or severe (n=13, 12%). Dialysis vintage was associated with severity of AV calcification (p=0.04). The 18 subjects with long-term warfarin exposure (36.7 +/- 19.7 months) were more likely to have severe AV calcification (p=0.04). The odds ratio of falling into a higher category of AV calcification following 18 months of warfarin was 3.77 (95% confidence ratio, 0.97-14.70; p=0.055). There was an association between lifetime months of warfarin exposure and severity of AV calcification (p=0.004) that was independent of dialysis vintage, calcium and calcitriol intake. CONCLUSIONS: The data suggest that warfarin may be associated with severity of AV calcification in HD patients and support the need for prospective studies.     

Extensive calcification of the mitral valve annulus in transcatheter aortic valve implants

 Open in a separate windowOBJECTIVESThis study sought to report the calcification pattern of the mitral valve annulus and its implications for procedural and safety outcomes in transcatheter aortic valve implantation.METHODSBetween November 2018 and September 2019, a total of 305 patients had transcatheter aortic valve implants at our institution. The extent of calcification of the mitral valve annulus was analysed, and the impact on safety outcomes was evaluated.RESULTSThe prevalence of mitral annular calcification (MAC) was 43%. Calcification of the mitral valve annulus was either less than or at least one-third of the posterior annulus (34% and 32%), the whole posterior annulus (28%) or the extension to the attachment of the anterior leaflets (7%). Severe circumferential MAC revealed moderate paravalvular leaks in 5/8 (63%) patients and was associated with right branch bundle block [odds ratio (OR) 2.01 (0.39–3.06); P = 0.098] and low cardiac output [OR 3.12 (1.39–7.04); P = 0.033]. Subannular calcification at the anterolateral trigonum represented a risk factor for left ventricular outflow tract injury [OR 3.54 (1.38–8.27); P = 0.001] in balloon-expandable valves, associated with relevant rhythm disorders [OR 2.26 (1.17–5.65); P = 0.014] and female gender (7/8, 88%). The 30-day all-cause mortality in circumferential MAC reaching into the anterior annulus (grade IV) compared to patients with less MAC (grade I–III) was 13% vs 2% with a mean valve size of 24.6 vs 25.7 mm.CONCLUSIONSExtensive MAC was associated with moderate paravalvular leaks, with implications for the prosthesis size and survival in transcatheter aortic valve implants. In severe MAC, we recommend implanting oversized self-expandable prostheses, the goal being to reduce the risk of right branch bundle block and paravalvular leaks.Subj collection122, 125     

Progression of aortic valve stenosis: TGF-beta1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis

BACKGROUND: Aortic valve stenosis characteristically progresses due to cuspal calcification, often necessitating valve replacement surgery. The present study investigated the hypothesis that TGF-beta1, a cytokine that causes calcification of vascular smooth muscle cells in culture, initiates apoptosis of valvular interstitial cells as a mechanistic event in cuspal calcification. METHODS: Noncalcified and calcified human aortic valve cusps were obtained at autopsy or at the time of cardiac surgery. The distributions within cusps of TGF-beta1, latent-TGF-beta1-associated peptide, and TGF-beta receptors were studied using immunohistochemistry. The effects of TGF-beta1 on mechanistic events contributing to aortic valve calcification were also investigated using sheep aortic valve interstitial cell (SAVIC) cultures. RESULTS: Immunohistochemistry studies revealed that calcific aortic stenosis cusps characteristically contained within the extracellular matrix qualitatively higher levels of TGF-beta1 than noncalcified cusps. Noncalcified normal valves demonstrated only focal intracellular TGF-beta1. Addition of TGF-beta1 to SAVIC cultures led to a cascade of events, including: cellular migration, aggregation, formation of apoptotic-alkaline phosphatase enriched nodules, and calcification of these nodules. The time course of these events in the SAVIC culture system was rapid with nodule formation with apoptosis by 72 hours, and calcification after 7 days. Furthermore, ZVAD-FMK, an antiapoptosis agent (caspase inhibitor), significantly inhibited calcification and apoptosis induced by TGF-beta1, but had no effect on nodule formation. However, cytochalasin D, an actin-depolymerizing agent, inhibited nodule formation, but not calcification. CONCLUSIONS: TGF-beta1 is characteristically present within calcific aortic stenosis cusps, and mediates the calcification of aortic valve interstitial cells in culture through mechanisms involving apoptosis.     

Decalcification of anterior cusp of mitral valve at marked calcification of aortic valve

Short-term and long-term results of surgical treatment were analyzed in 108 patients with aortic valve disease, complicated significant calcinosis spreading on anterior cusp of mitral valve. Mean age of the patients - 53,5±10,8 years (from 25 to 88 years). All patients underwent aortic valve replacement and decalcification of anterior cusp of mitral valve. Coronary bypass grafting was additionally carried out in 10 cases (from 1 to 5 shunts, 1,9 - in average). Hospital lethality was absent. Functional improvement of mitral valve was observed basing on postoperative echocardiography and remained in long-term period.     

Cardiac conduction defects associated with aortic and mitral valve calcification in dialysis patients

The prevalence of aortic valve and mitral valve or mitral annular calcification by echocardiography was studied in 66 dialysis patients and correlated with results of 24-h ambulatory and resting ECG data and 12-month survival. The well-known association of mitral valve or mitral annular calcification with cardiac conduction defects was confirmed. Those patients with mitral valve or mitral annular calcification demonstrated a higher prevalence of first-degree atrioventricular block and bundle branch block. Despite advanced age and these conduction defects, those patients with mitral valvular calcification did not show decreased survival at 12 months.     

老年高血压患者血压变异性与主动脉瓣钙化的关系

目的 探讨老年高血压患者血压变异性在其退行性主动脉瓣钙化中的作用和影响.方法 随机抽样2007年1月～2009年8月在笔者所在医院住院老年高血压患者164例为研究对象,行心脏超声及24h动态血压检查,根据超声中主动脉瓣钙化积分分为无钙化组（76例）和无钙化对照组（88例）;所有入选对象均排除对血压和瓣膜钙化有影响的疾病.观察两组收缩压、舒张压、血压变异性情况.结果 SDHVD总检出率为47.6%;男女性别间差异无统计学意义;SDHVD与高血压病程相关;随着收缩压变异系数增大,SDHVD发生率增大加,而舒张压变异系数与SDHVD无相关性.结论 老年高血压患者血压变异性减小与老年退行性心脏瓣膜病有关.     

Aortic valve calcification is mediated by a differential response of aortic valve interstitial cells to inflammation

Background

Although calcific aortic stenosis is common, calcification of the other three heart valves is not. The aortic valve interstitial cell (VIC) has been implicated in the pathogenesis of aortic stenosis. Proinflammatory stimulation of aortic VICs induces an osteogenic and inflammatory phenotypic change. We hypothesized that the VICs of the other heart valves do not undergo these changes. Using isolated human VICs from normal aortic, mitral, pulmonary, and tricuspid valves, our purpose was to compare the osteogenic response to proinflammatory stimulation via toll-like receptor 4 (TLR-4).

Materials and methods

Aortic, pulmonic, mitral, and tricuspid (n = 4 for each valve type) VICs were isolated from hearts valves explanted from patients undergoing cardiac transplantation. Cells were cultured and grown to confluence in passage 2–6 before treatment with Lipopolysaccharide (LPS) (100–200 ng/mL) for 24 or 48 h. Cells were characterized by immunofluorescent staining. TLR-4 expression was analyzed (immunoblotting, flow cytometry). Bone morphogenetic protein 2 and intercellular adhesion molecule 1 production were determined (immunoblotting). Monocyte chemoattractant protein 1 levels were determined by enzyme-linked immunosorbent assay. Statistics were by Mann–Whitney U test.

Results

TLR-4 stimulation induced bone morphogenetic protein 2 production only in aortic VICs (P < 0.05). Intra-cellular adhesion molecule 1 production and monocyte chemoattractant protein 1 secretion increased in a similar fashion among TLR-4-stimulated VICs from all four valves.

Conclusions

Proinflammatory stimulation induces an osteogenic phenotype in aortic VICs but not mitral, pulmonic, or tricuspid VICs. We conclude that this differential osteogenic response of aortic VICs contributes to the pathogenesis of calcific aortic stenosis.     

Kangaroo versus porcine aortic valve tissue--valve geometry morphology, tensile strength and calcification potential

OBJECTIVE: Valve related factors and patient related factors are responsible for calcification of valvular bioprostheses. Recent studies showed different donor and recipient species have different influences on the total calcification rate of bioprostheses. This study was performed to evaluate and compare Kangaroo aortic valve leaflets with porcine aortic valve leaflets. Experimental design. Prospective study. Setting. Cardio-thoracic experimental research of a university department. MATERIALS AND METHODS: Glutaraldehyde-fixed Kangaroo and porcine valve leaflets were evaluated in vitro according to valve geometry (internal diameter and leaflet thickness), morphology (light and electron microscopy) and tensile strength. In vivo evaluation consisted of implantation in a rat model for 8 weeks, Von Kossa stain for calcium and atomic absorption spectrophotometry for total extractable calcium content. RESULTS: Kangaroo valves indicated a smaller internal valve diameter as well as a thinner valve leaflet (p<0.01, ANOVA) at corresponding body weight, less proteoglycan spicules in the fibrosa, increased elasticity (p<0.05) and low calcification potential (p<0.01, confidence interval 95%). CONCLUSIONS: Kangaroo aortic valve leaflets have different valvular qualities compared to porcine valve tissue. Kangaroo valve leaflets are significantly superior to porcine valve leaflets as far as calcification is concerned. These results are encouraging and suggest further in vivo evaluation in a larger animal model before clinical application can be considered.     

A case of aortic bicuspid valve with thrombus formation without severe stenosis and calcification

We encountered a patient with a history of juvenile cerebral infarction with an unknown cause in whom a mass adhering to the aortic valve (AV) surface was observed on echocardiography performed upon the development of heart failure. Mild AV stenosis (AS) with moderate regurgitation was noted, and valve repair was applied. It was found during surgery that the AV was a bicuspid valve (BAV) without calcification, and the mass was an organized thrombus. Thrombus formation on the AV with severe AS in BAV has been reported, but the organic lesion in the AV was mild in this patient.     

C-reactive protein as a marker of severe calcification among patients with bicuspid aortic valve disease

Background. Bicuspid aortic valve (BAV) may be associated with aneurysmal dilatation of the ascending aorta, even after successful aortic valve replacement. There are as yet no biomarkers that correlate with the progression of such disease. Elevated levels of C-reactive protein (CRP), a marker of acute inflammation, are seen in chronic rheumatic valve disease, especially those with multivalvular disease, and have been shown to return to normal after valve replacement. We hypothesized that dilatation of the ascending aorta with BAV would be associated with ongoing inflammation, and, accordingly, elevated levels of CRP. Methods. High-sensitivity CRP levels [normal 0.02-0.8 mg/dl] were assayed from blood samples drawn in the operating room prior to cardiopulmonary bypass in 25 patients (4 female and 21 male, mean age 50 years, range 18-72 years) with bicuspid aortic valve disease undergoing valve replacement or repair. Preoperative cardiovascular risk factors for coronary artery disease, as well as valve function, area, and ascending aortic diameter based on echocardiogram were noted. Degree of valve calcification (none to minimal or moderate to severe) was recorded based on surgical observation or pathology report. None of the patients had active infections, tumors, or acute myocardial infarction. Results. There was no correlation of the CRP level to aortic diameter, valve area, patient age, gender, or body mass index (BMI). CRP levels were higher among patients with moderate-to-severe valvular calcification (n = 13, mean 0.711 ± 2.22 mg/dl) compared with none or minimal valvular calcification (n = 12, mean CRP 3.071 ± 5.62 mg/dl) (P = 0.0065). This difference remained statistically significant after excluding patients with coronary artery disease (n = 13). There was a trend for higher CRP level among patients with aortic stenosis (mean CRP 5.378 mg/dl) compared to those with aortic regurgitation (mean CRP 0.103 mg/dl) (P = 0.058). Conclusions. Elevated CRP among patients with BAV did not correlate with aortic diameter, but was associated with advanced calcific valve disease. This assay may prove useful in understanding the pathogenesis of calcification in this group of patients and to identify those with BAV at risk for progressive aortic valve disease.     

Aortic valve reconstruction using self-developed aortic valve plasty system in aortic valve disease

Aortic valve disease is usually treated by prosthetic valve replacement. We have performed aortic valve plasty (AVP) using glutaraldehyde-treated autologous pericardium. AVP was performed for 88 patients from April 2007 through August 2009. Sixty-five patients had aortic stenosis, and 23 patients had aortic regurgitation (AR). Twenty-one patients showed bicuspid aortic valves, and one patient showed quadricuspid valve. There were 43 males and 45 females. Their mean age was 70.6±10.5 years old. First, diseased leaflets excised. Then, the distance between each commissure was measured. The new leaflet were trimmed with an original template from a glutaraldehyde-treated autologous pericardium sample. Finally, the annular margin of the pericardial leaflet was running sutured to each annulus. There was no operative mortality or embolic event. Postoperative echocardiography revealed a mean peak pressure gradient (PG) of 19.0±9.1 mmHg one week after surgery. Thirty-two patients had echocardiography one year after surgery. The peak PG became 12.9±5.8 mmHg. Ten patients showed no AR, 20 patients showed trivial AR, and two patients showed mild AR. Freedom from reoperation is 100% at three years follow-up.     

Surgery for aortic valve disease with congenital bicuspid aortic valve

From January 1998 to December 2002, a total of 120 patients underwent aortic valve surgery at our institution. Of these, 26 patients (22%) had congenital bicuspid aortic valve (BAV). Main valvular lesion of BAV was aortic valve stenosis (AS) in 17 and regurgitation (AR) in 9. There was no significant difference in the aortic annular size between BAV and non-BAV cases measured by echocardiography preoperatively [22.8 +/- 2.0 mm versus 22.5 +/- 2.2 mm in AS (NS), and 25.4 +/- 2.4 mm versus 23.4 +/- 2.5 mm in AR (NS)]. At operation, however, supraannular type prosthetic valve was selected more frequently in BAV than in non-BAV because of the difficulty of implanting the proper size prosthetic valve in annular position in BAV [10/25 (40%) in BAV versus 18/91 (20%) in non-BAV (p < 0.05)]. Moreover, ascending aortic dimension in BAV cases was significantly larger than in non-BAV cases [43.7 +/- 7.3 mm versus 39.6 +/- 7.3 mm (p<0.05)]. These features were more prominent in non-raphe BAV cases. These results suggested that operative procedure including prosthetic valve selection needs careful consideration in BAV especially no-raphe patients.     

Quadricuspid aortic valve

A case of quadricuspid aortic valve is described. The anomaly was unexpectedly found during operation for aortic valve replacement in a 70-year-old woman. Macroscopic and histological examinations of the valve showed no sign of previous inflammatory disease. Quadricuspid aortic valve must be considered, therefore, a malformation capable of leading to severe valve failure in later life.