Extent Of Aortic Valve Calcification Research Articles

Regular Dietary Intake of Palmitate Causes Vascular and Valvular Calcification in a Rabbit Model.

Aims: Palmitic acid (PA) and oleic acid (OA) are two main dietary fatty acids. Dietary intake of PA has been associated with cardiovascular disease risk, and the effect of OA remains uncertain. Our study aimed to assess the effect of a short-term intake of lard, as source of PA and OA, on aorta and aortic valve.Methods and Results: Rabbits were fed with two lard-enriched diets, containing either elevated levels of PA or of both PA and OA as compared to chow diet. After 16 weeks of each diet, calcification was observed in the aortic intima and in the aortic valve. The extent of calcification did not differ between the two diets. In contrast, rabbits fed chow diet did not develop any calcification. In blood, PA enrichment resulted in decreased lymphocyte and monocyte counts and increased levels of hemoglobin and haematocrit. Levels of the calcification inhibitor fetuin-A were also diminished, whereas creatinine levels were raised. Of note, none of the diets changed cholesterol levels in LDL or HDL. Comprehensive quantitative lipidomics analysis identified diet-related changes in plasma lipids. Dietary PA enrichment led to a drop of polyunsaturated fatty acids (PUFA), in particular of linoleic acid in cholesteryl esters, triglycerides and diacylglycerols (DAG). Ratios of PA to 18-carbon PUFA in DAG were positively correlated with the extent of aortic valve calcification, and inversely with monocyte counts. PA content in blood correlated with aorta calcification.Conclusions: Regular dietary PA intake induces vascular and valvular calcification independently of traditional risk factors. Our findings raise awareness about PA-rich food consumption and its potential deleterious effect on cardiovascular health.

The association between aortic valve calcification, cardiovascular risk factors, and cardiac size and function in a general population

To determine the presence and extent of aortic valve calcification (AVC) quantified by non-contrast cardiac computed tomography (NCCT), to determine the association between traditional cardiovascular risk factors and AVC score, and to evaluate the association between AVC and cardiac size and function assessed by echocardiography, in a general population aged 65-75years. A random sample of 2060 individuals were invited to undergo NCCT through which their AVC score was assessed. Individuals with an AVC score ≥ 300 arbitrary units (AU) were invited for a transthoracic echocardiography together with age-matched controls. Descriptive statistics and multiple regression analyses were performed to identify risk factors associated with AVC and to describe associations between AVC score and echocardiographic findings. Of 2060 individuals invited 664 males and 636 females participated. Among those, 455 (68.5%) of males and 358 (56.3%) of females had AVC scores > 0 AU. The median AVC score was 6 AU (IQR 0-3064). Seventy-seven (11.6%) males and 20 (3.1%) females had an AVC score ≥ 300 AU. In a multiple regressionanalysis, age, sex, prior cardiovascular disease, smoking, and hypertension were associated with AVC score, while diabetes, hypercholesterolemia and kidney function were not. Individuals with AVC ≥ 300 AU had higher peak and mean aortic valve gradient, smaller indexed aortic valve area, greater left ventricular mass, and larger left atrial (LA) volume. In a random population sample of individuals aged 65-75years, AVC was common and associated with most known cardiovascular risk factors. AVC ≥ 300 AU was associated with concentric remodeling and LA dilatation.

Accuracy of device landing zone calcium volume measurement with contrast-enhanced multidetector computed tomography

BackgroundThe extent of aortic valve calcification is an important determinant of procedural success in transcatheter aortic valve implantation (TAVI). We sought to validate device landing zone calcium volume (DLZ-CV) measurements on contrast-enhanced multidetector computed tomography (MDCT) with non-contrast-enhanced scans as reference. MethodsWe determined DLZ-CV in 141 patients undergoing transfemoral TAVI. Non-contrast-enhanced images were analyzed using a threshold of 130 HU as reference (DLZ-CV130). For contrast-enhanced scans, we applied various thresholds including 450 HU (DLZ-CV450), 850 HU (DLZ-CV850), mean aortic attenuation (AttenAo) + 2 SD (DLZ-CV2SD), AttenAo + 4 SD (DLZ-CV4SD), AttenAo + 4 SD + 5 mm3 volume filter (DLZ-CV4SD+), and based on visual estimation (DLZ-CVvis). We compared DLZ-CV values between patients with versus without paravalvular leak (PVL), and between patients with versus without post-dilatation stratified by the type of prosthesis. ResultsAll DLZ-CV measurements on contrast-enhanced scans significantly differed from DLZ-CV130 (p < 0.001 for all comparisons). The best approximation to DLZ-CV130 was achieved with DLZ-CV4SD+ (508 mm3 [332–772]; Pearson correlation: R = 0.87, p < 0.001; Bland-Altman: mean difference 1339 mm3 [limits of agreement 79;2600]). Moreover, DLZ-CV4SD+ allowed for discrimination of PVL ≥1° or the need for post-dilatation in patients receiving self-expanding prostheses. Procedural outcome using balloon-expandable prostheses was independent of DLZ-CV. ConclusionMeasurement of DLZ-CV using contrast-enhanced scans with unadjusted thresholds results in incorrect estimation of the calcium volume. The use of a scan-specific individual HU threshold including a volume filter (DLZ-CV4SD+) provides the best approximation to the reference and allows for discrimination of PVL ≥ 1° in patients receiving the Acurate neo prosthesis.

Comparison of outcomes using balloon-expandable versus self-expanding transcatheter prostheses according to the extent of aortic valve calcification.

Device landing zone (DLZ) calcification is an important determinant of procedural success in transcatheter aortic valve implantation (TAVI). To evaluate the impact of DLZ calcification on procedural outcome with different types of transcatheter heart valves (THVs). Aortic valve calcium density (AVCdens) was determined by non-contrast-enhanced computed tomography in 1232 patients undergoing transfemoral TAVI. We stratified the outcome data according to the extent of AVCdens (mild, moderate, severe) and compared balloon-expandable (BE) with self-expanding (SE) THV. Moreover, THVs were subdivided according to their radial force (BE: high; SEmod: moderate; SElow: low). With BE THV, PVR ≥2° (2.1 vs. 7.9%; p<0.001), post-dilatation (12.3 vs. 36.6%; p<0.001), malpositioning (8.4 vs. 13.0%; p=0.01), device embolization (0.4 vs. 2.6%; p=0.004), and the need for a second valve (1.2 vs. 3.6%; p=0.01) were less frequent than with SE devices, but mean transaortic gradients at discharge were higher [12.0mmHg (8.0-15.0) vs. 9.0mmHg (6.0-11.0); p<0.001], and aortic root injury was more frequent (2.7 vs. 0.8%; p =0.01). In cases of severe calcification, differences between BE and SE THV regarding PVR, post-dilatation, and hemodynamics were mostly pronounced, followed by patients with moderateAVCdens. In cases with low AVCdens, the best outcomes with respect to PVR, pacemaker implantation, and hemodynamics were achieved with SElow THV. In severe and moderate DLZ calcification, BE devices may have advantages, whereas in mild DLZ calcification, SElow THV showed the most favorable profile.

Severe and Asymptomatic Aortic Stenosis Management Challenge: Knowing That We Do Not Really Know.

The clinical management of asymptomatic patients with severe aortic valve stenosis (AS) may be challenging. Indeed, there is substantial controversy over the optimal timing of intervention for these patients, as some advocate early intervention while others urge for a conservative management until symptom onset. In the meantime of randomized clinical trials aiming to compare both strategies of management, an integrative approach including several imaging modalities as well as biomarkers of the myocardial damage may help to improve the risk stratification of patients with asymptomatic severe AS and individualize strategy of treatment. The extent of aortic valve calcification, semi-quantitatively assessed by echocardiography but better fully quantitatively measured by computed tomography (CT), provides incremental value to predict rapid disease progression and adverse event and thus could be a potential trigger for early referral to intervention or guide the timing of clinical follow-up. In addition, the assessment of disease activity using positron emission tomography, combined with CT calcium scoring, may also help to better predict the disease progression. The comprehensive assessment of left ventricular (LV) function using speckle-tracking echocardiography and/or cardiac magnetic resonance may provide useful information regarding the actual repercussion of AS on the myocardium. Besides imaging modalities, the measurement of several circulating biomarkers associated with the extent of the myocardial damage may also improve the risk stratification of asymptomatic patients with severe AS and help guiding management. Finally, it should be emphasized that a personalized medicine, including this comprehensive integrative approach in heart valve clinics, should be advocated for the management of these challenging patients.

Increased Aortic Valve Calcification in Familial Hypercholesterolemia: Prevalence, Extent, and Associated Risk Factors

BackgroundFamilial hypercholesterolemia is typically caused by LDL receptor (LDLR) mutations that result in elevated levels of LDL cholesterol (LDL-C). In homozygous FH, the prevalence of aortic valve calcification (AoVC) reaches 100% and is often symptomatic. ObjectivesThe objective of this study was to investigate the prevalence, extent, and risk-modifiers of AoVC in heterozygous FH (he-FH) that are presently unknown. MethodsAsymptomatic patients with he-FH and 131 non-familial hypercholesterolemia controls underwent CT computed tomography calcium scoring. AoVC was defined as the presence of calcium at the aortic valve leaflets. The extent of AoVC was expressed in Agatston units, as the AoVC-score. We compared the prevalence and extent of AoVC between cases and controls. In addition, we investigated risk modifiers of AoVC, including the presence of LDLR mutations without residual function (LDLR-negative mutations), maximum untreated LDL-cholesterol (maxLDL), LDL-C, blood pressure, and coronary artery calcification (CAC). ResultsWe included 145 asymptomatic patients with he-FH (93 men; mean age 52 ± 8 years) and 131 non-familial hypercholesterolemia controls. The prevalence (%) and AoVC-score (median, IQR) were higher in he-FH patients than in controls: 41%, 51 (9–117); and 21%, 21 (3–49) (p < 0.001 and p = 0.007). Age, untreated maxLDL, CAC, and diastolic blood pressure were independently associated with AoVC. LDLR-negative mutational he-FH was the strongest predictor of the AoVC-score (OR: 4.81; 95% CI: 2.22 to 10.40; p = <0.001). ConclusionsCompared to controls, he-FH is associated with a high prevalence and a large extent of subclinical AoVC, especially in patients with LDLR-negative mutations, highlighting the critical role of LDL-C metabolism in AoVC etiology.

Fibroblast growth factor 23 and parathyroid hormone predict extent of aortic valve calcifications in patients with mild to moderate chronic kidney disease

BackgroundCardiac valve calcifications are present in dialysis patients and regarded as dependent on a deranged mineral metabolism. Few data are available for patients with chronic kidney disease (CKD) not on dialysis. This study evaluates the potential association between the extent of cardiac valve calcification and levels of intact parathyroid hormone (i-PTH), phosphorus, calcium, 25-OH vitamin D, fibroblast growth factor 23 (FGF-23), Klotho and C-reactive protein (CRP) simultaneously measured in patients with mild to moderate CKD.MethodsConsecutive non-hospitalized patients referring to five nephrology units were evaluated. Inclusion criteria were age >18 years, CKD Stages 3–4, and the presence of aortic and/or mitral valve calcification assessed by echocardiography as routinely clinical evaluation. Patients underwent clinical examination and routine biochemistry. Baseline i-PTH, phosphorus, calcium, 25-OH vitamin D, FGF-23, Klotho and CRP were simultaneously ascertained.ResultsExtent of aortic valve calcification (n = 100 patients) was moderate in 68 patients and mild in the remaining patients. Mitral valve calcification (n = 96 patients) score was 1, 2 and 3 in 61, 34 and 1 patients, respectively. In univariate analysis, no association was found between extent of mitral valve calcification and markers of mineral metabolism and CRP; aortic valve extent of calcification was positively associated with i-PTH (r2 = 0.212; P = 0.03) and FGF-23 (r2 = 0.272; P = 0.01), and negatively with Klotho (r2 = −0.208; P = 0.04). In multivariable analysis, extent of aortic valve calcification was associated with FGF-23 (P = 0.01) and PTH (P = 0.01) levels.ConclusionsExtent of aortic valve calcification is associated to FGF-23 and PTH in naïve CKD patients with mild to moderate CKD. Further studies should examine whether FGF-23 assay should be included in routine clinical evaluation of CKD as part of cardiovascular risk stratification.

Aortic annulus eccentricity before and after transcatheter aortic valve implantation: Comparison of balloon-expandable and self-expanding prostheses

IntroductionThe geometry of the aortic annulus and implanted transcatheter aortic valve prosthesis might influence valve function. We investigated the influence of valve type and aortic valve calcification on post-implant geometry of catheter-based aortic valve prostheses. MethodsEighty consecutive patients with severe aortic valve stenosis (mean age 82±6 years) underwent computed tomography before and after TAVI. Aortic annulus diameters were determined. Influence of prosthesis type and degree of aortic valve calcification on post-implant eccentricity were analysed. ResultsAortic annulus eccentricity was reduced in patients after TAVI (0.21±0.06 vs. 0.08±0.06, p<0.0001). Post-TAVI eccentricity was significantly lower in 65 patients following implantation of a balloon-expandable prosthesis as compared to 15 patients who received a self-expanding prosthesis (0.06±0.05 vs. 0.15±0.07, p<0.0001), even though the extent of aortic valve calcification was not different. After TAVI, patients with a higher calcium amount retained a significantly higher eccentricity compared to patients with lower amounts of calcium. ConclusionsPatients undergoing TAVI with a balloon-expandable prosthesis show a more circular shape of the implanted prosthesis as compared to patients with a self-expanding prosthesis. Eccentricity of the deployed prosthesis is affected by the extent of aortic valve calcification.

Arterial Wave Reflection and Aortic Valve Calcification in an Elderly Community-Based Cohort

Aortic valve calcification (AVC) without stenosis is common in the elderly, is associated with cardiovascular morbidity and mortality, and may progress to aortic valve stenosis. Arterial stiffness and pulse-wave reflection are important components of proximal aortic hemodynamics, but their relationship with AVC is not established. To investigate the relationship of arterial wave reflection and stiffness with AVC, pulse wave analysis and AVC evaluation by echocardiography were performed in 867 participants from the Cardiovascular Abnormalities and Brain Lesions study. Participants were divided into four categories on the basis of the severity and extent of AVC: (1) none or mild focal AVC, (2) mild diffuse AVC, (3) moderate to severe focal AVC, and (4) moderate to severe diffuse AVC. Central blood pressures and pulse pressure, total arterial compliance, augmentation index, and time to wave reflection were assessed using applanation tonometry. Indicators of arterial stiffness and wave reflection were significantly associated with AVC severity, except for central systolic and diastolic pressures and time to reflection. After adjustment for pertinent covariates (age, sex, race/ethnicity, and estimated glomerular filtration rate), only augmentation pressure (P = .02) and augmentation index (P = .002) were associated with the severity of AVC. Multivariate logistic regression analysis revealed that augmentation pressure (odds ratio per mm Hg, 1.14; 95% confidence interval, 1.02-1.27; P = .02) and augmentation index (odds ratio per percentage point, 1.07; 95% confidence interval, 1.01-1.13; P = .02) were associated with an increased risk for moderate to severe diffuse AVC, even when central blood pressure value was included in the same model. Arterial wave reflection is associated with AVC severity, independent of blood pressure values. Increased contribution of wave reflection to central blood pressure could be involved in the process leading to AVC.

Aortic annulus eccentricity before and after transcatheter aortic valve implantation: comparison of balloon-expandable and self-expandable prostheses

Purpose: A non-circular geometry of the aortic annulus and implanted prosthesis after transcatheter aortic valve implantation (TAVI) might be relevant for short- and long-term valve function. We investigated the influence of valve type and aortic valve calcification on post-implant geometry of the catheter-based aortic valve prostheses. Methods: Eighty consecutive patients with severe aortic valve stenosis (mean age 82±6 years, 43 (53.7%) male, mean logistic Euroscore 27±14) underwent dual source computed tomography (2x64x0.6 mm or 2x128x0.6 mm) before and after TAVI. The minimal and maximal aortic annulus diameters were determined in multiplanar reconstructions exactly aligned with the annulus plane. Eccentricity of the aortic annulus or prosthesis was defined as 1-(minimal/maximal diameter). Influence of prosthesis type and degree of aortic valve calcification on post-implant eccentricity was analysed. Results: Mean aortic annulus dimensions were 21.4±2.2 mm (short diameter) by 27.0±2.4 mm (long-diameter) prior to valve implantation. Following TAVI, mean diameters were 19.9±2.0 mm by 21.6±2.0 mm. The aortic annulus showed a significantly higher eccentricity in all patients before than after TAVI (0.21±0.06 vs. 0.08±0.06, p<0.0001). Post-TAVI eccentricity was significantly lower in 65 (81.2%) patients following implantation of a balloon-expandable Edwards Sapien prosthesis as compared to 15 (18.8%) patients after a self-expandable Medtronic CoreValve prosthesis (0.06±0.05 vs. 0.15±0.07, p<0.0001). There was no significant difference regarding the extent of aortic valve calcification in patients in whom balloon-expandable or self-expandable aortic valve prostheses were implanted (mean calcium volume of 583.4±421.1 mm3 vs. 509.7±362.6 mm3, p=0.66). After TAVI, patients with a higher calcium burden (mean 1048.1±323.7mm3) showed a significantly higher eccentricity compared to patients with a lower calcium burden (mean 187.5±82.0 mm3; Eccentricity of 0.08±0.06 vs. 0.05±0.03, p=0.02). Conclusions: Catheter-based implantation of aortic valve prosthesis reduces eccentricity of the aortic annulus. Patients undergoing TAVI with a balloon-expandable prosthesis are more likely to demonstrate a circular shape of the implanted prosthesis as compared to patients with a self-expandable prosthesis. Eccentricity of the deployed prosthesis is affected by the extent of aortic valve calcification. Further studies need to assess the influence of prosthesis eccentricity on long-term outcome.

Association Between Aortic Valve Calcification and Myocardial Ischemia, Especially in Asymptomatic Patients

Aortic valve calcification (AVC) is recognized as a manifestation of systemic arteriosclerosis. However, it is unclear whether AVC is associated with myocardial ischemia. Stress myocardial perfusion SPECT (MPS) is widely used for the diagnosis of myocardial ischemia. However, routine MPS is not recommended, particularly in asymptomatic patients. Accordingly, we investigated the hypothesis that the presence of AVC is strongly associated with inducible myocardial ischemia, even among asymptomatic patients. We investigated 669 consecutive patients who underwent both adenosine stress (201)Tl MPS and echocardiography. We evaluated the extent and severity of myocardial ischemia by the summed difference score (SDS). We defined the presence of myocardial ischemia as SDS ≥ 3 and moderate to severe ischemia as SDS ≥ 8. We classified the severity of AVC according to the number of affected aortic leaflets. We also compared the mean SDS and the prevalence of SDS ≥ 3 and SDS ≥ 8 among patients stratified by the severity of AVC. The presence of AVC was significantly associated with myocardial ischemia (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.10-2.23; P = 0.013) and moderate to severe ischemia (OR, 2.16; 95% CI, 1.26-3.80; P = 0.0061). In 311 asymptomatic patients, AVC was strongly associated with moderate to severe ischemia (OR, 4.31; 95% CI, 1.67-12.8; P = 0.0043). However, the SDS value and the prevalence of SDS ≥ 3 and SDS ≥ 8 did not increase with increasing number of affected aortic leaflets. The presence of AVC may be associated with the presence of myocardial ischemia, particularly in asymptomatic patients. However, we found no association between the extent of AVC and inducible myocardial ischemia. The presence of AVC may be a useful anatomic marker to help identify patients at high risk of myocardial ischemia, particularly asymptomatic patients.

Impact of aortic valve calcification on the outcome of transcatheter aortic valve implantation: Results from the prospective multicenter German TAVI registry

Transcatheter aortic valve implantation (TAVI) is an emerging technology in patients with severe aortic stenosis. Whether the degree of aortic valve calcification impacts the outcome after TAVI has not been thoroughly evaluated. We analyzed data from the prospective multicenter German TAVI registry, including 1,365 patients as of July 2010. Patients were divided into three groups, based on the degree of aortic valve calcification: mild (n = 67), moderate (n = 392), and severe (n = 906) valve calcification, determined by visual estimation by the operator. Mean age was 81.7 ± 6.2 years; mean logistic EUROscore was 20.6 ± 13.7%. Patients with severe aortic valve calcification had a higher mean and peak-to-peak gradient before the intervention (P < 0.0001). Technical success was achieved in 97%, similar in each group. The Medtronic CoreValve was implanted in 80.8%, the Sapien Edwards prosthesis in the remaining cases. The duration of the procedure and fluoroscopy was higher in the group with severe calcification (P < 0.01 for procedure and P < 0.05 for fluoroscopy). During the periprocedural period there were no differences among the groups regarding in-hospital death, cerebrovascular events, myocardial infarction, thromboembolic events, aortic dissection, or severe vascular complications. Furthermore, there was no significant difference in postprocedural aortic mean gradient (7.0 mm Hg vs. 5.6 mm Hg vs. 6.3 mm Hg; P = 0.07), in residual aortic regurgitation (74% vs. 72% vs. 68%; P = 0.3) or postprocedure pacemaker implantation (38% vs. 30.4% vs. 34.2%; P = 0.35). During 30-day follow up there was no difference in regard to the number of death, strokes, and myocardial infarctions. Our results of a real-world registry suggest that the extent of aortic valve calcification does not influence the success or procedural outcome significantly.

Predictors of Outcome in Severe, Asymptomatic Aortic Stenosis

Whether to perform valve replacement in patients with asymptomatic but severe aortic stenosis is controversial. Therefore, we studied the natural history of this condition to identify predictors of outcome. During 1994, we identified 128 consecutive patients with asymptomatic, severe aortic stenosis (59 women and 69 men; mean [+/-SD] age, 60+/-18 years; aortic-jet velocity, 5.0+/-0.6 m per second). The patients were prospectively followed until 1998. Follow-up information was available for 126 patients (98 percent) for a mean of 22+/-18 months. Event-free survival, with the end point defined as death (8 patients) or valve replacement necessitated by the development of symptoms (59 patients), was 67+/-5 percent at one year, 56+/-5 percent at two years, and 33+/-5 percent at four years. Five of the six deaths from cardiac disease were preceded by symptoms. According to multivariate analysis, only the extent of aortic-valve calcification was an independent predictor of outcome, whereas age, sex, and the presence or absence of coronary artery disease, hypertension, diabetes, and hypercholesterolemia were not. Event-free survival for patients with no or mild valvular calcification was 92+/-5 percent at one year, 84+/-8 percent at two years, and 75+/-9 percent at four years, as compared with 60+/-6 percent, 47+/-6 percent, and 20+/-5 percent, respectively, for those with moderate or severe calcification. The rate of progression of stenosis, as reflected by the aortic-jet velocity, was significantly higher in patients who had cardiac events (0.45+/-0.38 m per second per year) than those who did not have cardiac events (0.14+/-0.18 m per second per year, P<0.001), and the rate of progression of stenosis provided useful prognostic information. Of the patients with moderately or severely calcified aortic valves whose aortic-jet velocity increased by 0.3 m per second or more within one year, 79 percent underwent surgery or died within two years of the observed increase. In asymptomatic patients with aortic stenosis, it appears to be relatively safe to delay surgery until symptoms develop. However, outcomes vary widely. The presence of moderate or severe valvular calcification, together with a rapid increase in aortic-jet velocity, identifies patients with a very poor prognosis. These patients should be considered for early valve replacement rather than have surgery delayed until symptoms develop.