Association of fetuin-A levels with the progression of aortic valve calcification in non-dialyzed patients.

AIMS: Fetuin-A has been identified as a potent circulating inhibitor of ectopic calcification. We investigated the relationship between baseline fetuin-A serum levels and the rate of progression of aortic valve calcification (AVC) in non-dialyzed patients with aortic valve disease (AVD). METHODS AND RESULTS: Seventy-seven patients (mean age 70 +/- 8 years) with echocardiographically proven AVD were collected. In all patients, serum fetuin-A levels, creatinine, calcium, lipid parameters, and C-reactive protein were measured at baseline. For quantification of AVC progression, all patients underwent multislice spiral computed tomography examinations at baseline and after a mean follow-up of 12.6 +/- 1.4 months (range 7-18 months). In a multifactorial analysis of covariance including fetuin-A levels, baseline AVC score, the covariables sex, age, body mass index, C-reactive protein, glomerular filtration rate, serum lipids, diabetes, smoking status, and hypertension, only serum fetuin-A levels significantly predict the progression of AVC (P < 0.001). Post hoc analysis demonstrated that patients with baseline fetuin-A levels lower than the median of the cohort (0.72 g/L) showed a significantly higher increase of AVC scores (34.6 +/- 31.4%) than patients with fetuin-A levels larger than the median (10.0 +/- 11.2%, P < 0.001) despite comparable baseline AVC scores. In addition, fetuin-A levels were associated with major adverse clinical events (MACE; P = 0.03). CONCLUSION: Serum levels of the calcification inhibitor fetuin-A are associated with the progression of AVC and MACE, independent of the renal function and inflammation.

Relation of circulating Matrix Gla-Protein and anticoagulation status in patients with aortic valve calcification.

Matrix-Gla Protein (MGP) is a vitamin K-dependent protein acting as a local inhibitor of vascular calcification. Vitamin K-antagonists (oral anticoagulant; OAC) inhibit the activation of MGP by blocking vitamin K-metabolism. The aim of this study was to investigate the effect of long-term OAC treatment on circulating MGP levels in humans and on MGP expression in mice. Additionally, we tested the association between circulating inactive MGP (ucMGP) levels and the presence and severity of AVC in patients with aortic valve disease (AVD). We analysed circulating ucMGP levels in 191 consecutive patients with echocardiographically proven calcific AVD and 35 control subjects. The extent of AVC in the patients was assessed by multislice spiral computed tomography. Circulating ucMGP levels were significantly lower in patients with AVD (348.6 +/- 123.1 nM) compared to the control group (571.6 +/- 153.9 nM, p < 0.001). Testing the effect of coumarin in mice revealed that also the mRNA expression of MGP in the aorta was downregulated. Multifactorial analysis revealed a significant effect of glomerular filtration rate and long-term OAC therapy on circulating ucMGP levels in the patient group. Subsequently, patients on long-term OAC had significantly increased AVC scores. In conclusion, patients with calcific AVD had significantly lower levels of circulating ucMGP as compared to a reference population, free of coronary and valvular calcifications. In addition, our data suggest that OAC treatment may decrease local expression of MGP, resulting in decreased circulating MGP levels and subsequently increased aortic valve calcifications as an adverse side effect.

Relation of end-diastolic wall thickness and the residual rim of viable myocardium by magnetic resonance imaging to myocardial viability assessed by fluorine-18 deoxyglucose positron emission tomography.

End-diastolic wall thickness (EDWT) and thickness of the residual non-contrast-enhanced myocardial rim have been suggested as markers for the assessment of myocardial viability by cardiovascular magnetic resonance (CMR) imaging. This study compared these parameters as derived from contrast-enhanced CMR images for the prediction of myocardial viability as determined by fluorine-18 deoxyglucose positron emission tomography (FDG-PET). Twenty-two patients with ischemic cardiomyopathy (ejection fraction 31 +/- 11%) were investigated. For contrast-enhanced CMR imaging, a standard inversion-recovery sequence was used. FDG-PET was performed using a hyperinsulinemic-euglycemic clamp. Data were analyzed with a 17-segment model. Of 146 severely dysfunctional segments, 112 were assessed as viable and 34 as nonviable by nuclear imaging. Using receiver-operator characteristic analysis, areas under the curve were 0.95 for unenhanced myocardial rim (95% confidence interval 0.92 to 0.98) and 0.86 for EDWT (95% confidence interval 0.80 to 0.93, p <0.001 vs unenhanced myocardial rim) for the prediction of viability as assessed by FDG-PET. Cutoffs of 5.4 mm for EDWT and 3.0 mm for unenhanced myocardial rim were found to optimally differentiate viability by FDG-PET. In 25 segments with divergent results, 94% of segments with an EDWT < or =5.4 mm and an unenhanced myocardial rim >3.0 mm were scored as viable by FDG-PET, whereas 57% of segments with an EDWT >5.4 mm and an unenhanced myocardial rim < or =3.0 mm were scored nonviable with the reference technique. In conclusion, unenhanced myocardial rim is superior to EDWT for the prediction of myocardial viability as determined by FDG-PET and may be clinically useful for assessment of myocardial viability in patients with ischemic cardiomyopathy and regional wall thinning.

Quantification of aortic valve calcification using multislice spiral computed tomography: comparison with atomic absorption spectroscopy.

OBJECTIVES: Multislice spiral computed tomography (MSCT) allows the in vivo detection of valvular calcification. The aim of this study was to validate the quantification of aortic valve calcification (AVC) by MSCT with in vitro measurements by atomic absorption spectroscopy. METHODS: In 18 patients with severe aortic stenosis, 16 detector row MSCT (SOMATOM Sensation 16, Siemens, Forchheim, Germany with scan parameters as follows: 420 milliseconds tube rotation time, 12 x 0.75 mm collimation, tube voltage 120 KV) was performed before aortic valve replacement. Images were reconstructed at 60% of the RR interval with an effective slice thickness of 3 mm and a reconstruction increment of 2 mm. AVC was assessed using Agatston AVC score, mass AVC score, and volumetric AVC score. After valve replacement, the calcium content of the excised human stenotic aortic valves was determined in vitro using atomic absorption spectroscopy. RESULTS: The mean Agatston AVC score was 3,842 +/- 1,790, the mean volumetric AVC score was 3,061 +/- 1,406, and mass AVC score was 888 +/- 492 as quantified by MSCT. Atomic absorption spectroscopy showed a mean true calcification mass (Ca5(PO4)3OH) of 19 +/- 8 mass%. There was a significant correlation between in vivo AVC scores determined by MSCT and in vitro mean true calcification mass (r = 0.74, P = 0.0004 for mass AVC score, r = 0.79, P = 0.0001 for volumetric AVC score and r = 0.80, P = 0.0001 for Agatston AVC score) determined by atomic absorption spectroscopy. Linear regression analysis showed a significant association between the degree of hydroxyapatite (given in mass%) in the aortic valve and the degree of AVC (R = 0.74, F = 19.6, P = 0.0004 for mass AVC score, R = 0.80, F = 29.3, P = 0.0001 for Agatston AVC score and R = 0.79, F = 27.3, P = 0.0001 for volumetric AVC score) assessed by MSCT. CONCLUSION: MSCT allows accurate in vivo quantification of aortic valve calcifications.

Relation of oral anticoagulation to cardiac valvular and coronary calcium assessed by multislice spiral computed tomography.

Vitamin K antagonists, known as oral anticoagulants, affect the synthesis and function of the matrix Gla protein, which is a potent inhibitor of tissue calcification. We performed multislice spiral computed tomography in 86 patients (53 men, mean age 71 +/- 8 years) with calcific aortic valve disease to quantitate the amount of calcification in the aortic valve and coronary arteries. Patients with long-term oral anticoagulation therapy (mean duration 88 +/- 113 months; n = 23) were compared with those without anticoagulation (n = 63). No differences were found in the demographic, clinical, or echocardiographic characteristics between the 2 study groups. Patients on oral anticoagulant therapy had increased coronary calcium (coronary Agatston score 1,561 +/- 1,141 vs 738 +/- 978, respectively; p = 0.024) and valvular calcium (valvular Agatston score 2,410 +/- 1,759 vs 1,070 +/- 1,085, respectively; p = 0.002) compared with patients without anticoagulation treatment. The results of our study have demonstrated that oral anticoagulation may be associated with increased valvular and coronary calcium in patients with aortic valve disease, presumably due to decreased activation of the matrix Gla protein.

Preliminary experience in the assessment of aortic valve calcification by ECG-gated multislice spiral computed tomography.

BACKGROUND: The aim was to correlate the degree of valvular calcification in patients with aortic stenosis determined by retrospectively electrocardiogram (ECG)-gated multislice spiral computed tomography with stenosis severity assessed by cardiac catheterization. METHODS: Prospective study on 41 patients (18 men, mean age 71+/-8 years) with aortic stenosis, who underwent four detector row multislice spiral computed tomography and cardiac catheterization. Severity of aortic stenosis was classified by cardiac catheterization. Aortic valve area, peak to peak and mean transvalvular gradients were correlated with the degree of calcification determined by multislice spiral computed tomography. Aortic valve calcification was assessed using aortic Agatston score, aortic mass score and aortic volume score. RESULTS: All measured aortic valve calcification scores were significantly higher in patients with severe aortic stenosis (n=29) than in patients with moderate (n=7) or mild aortic stenosis (n=5, p<0.001). Aortic valve calcification scores correlated significantly with aortic valve area (r=-0.49, p=0.001 for aortic mass score) and with peak to peak (r=0.68, p<0.001) and mean (r=0.60, p<0.001) transvalvular gradients. CONCLUSIONS: Severity of aortic valve calcification assessed by cardiac multislice spiral computed tomography is inversely related to aortic valve area and positively correlated with transvalvular gradients. Based on this preliminary data larger studies should be performed with echocardiography as a reference standard in order to validate this new information and its utility in the clinical management of the patient.

[Significance of transesophageal echocardiography in daily clinical practice]. / Stellenwert der transösophagealen Echokardiographie in der klinischen Praxis.

Transesophageal echocardiography (TEE) has opened a new window to the heart. Its success rate is impressive. In less than 2 decades it has become an integral part of pediatric and adult cardiology as well as cardiac surgery and anesthesiology. The range of indications has broadened since its introduction almost 20 years ago. The combination of unique morphological and hemodynamic information of exceptional diagnostic quality and the possibility to use this diagnostic method as a bedside tool in the intensive care unit and the operating room guarantee that this diagnostic modality will maintain its firm place in the diagnostic armamentarium of cardiologists and anesthesiologists, besides novel and emerging imaging modalities such as cardiac magnetic resonance imaging (MRI) and multislice computed tomography (MSCT). Technical improvements in transducer technology and the development of miniaturized matrix transducers may, in the near future, allow real-time three-dimensional viewing of the heart even from the esophagus. It is anticipated that this will further increase the diagnostic potential of the technique and its importance for guiding of therapeutic procedures.

[Prevalence and pathogenesis of aortic valve calcifications]. / Prävalenz und Pathogenese von Aortenklappenkalzifikationen.

BACKGROUND: Calcific aortic valve disease is present in more than 25% of patients > 65 years of age and is associated with a 50% increased risk of cardiovascular events. The clinical significance of aortic valve calcification detected incidentally by radiologic examinations, especially on CT scans of the chest, was unknown. Concerning the multifactorial pathogenesis of aortic valve calcification, recent data indicate that, besides other factors, also the regulators of calcification play a key role in the disease process. PURPOSE: This study aims to give an overview of the prevalence and clinical significance of incidentally detected aortic valve calcifications. Moreover, the role calcification inhibitors in the pathogenesis of aortic valve calcification is discussed.

Prevalence and clinical importance of aortic valve calcification detected incidentally on CT scans: comparison with echocardiography.

PURPOSE: To evaluate retrospectively the prevalence and grade of aortic valve calcification incidentally detected on chest multi-detector row computed tomographic (CT) scans and to compare the grade of calcification with the severity of aortic valve disease as assessed with echocardiography. MATERIALS AND METHODS: Patient informed consent was waived by the institutional board on medical ethics that approved this study. The authors identified 402 patients (231 men and 171 women; mean age, 62.5 years +/- 12.1) of 1820 patients who underwent chest multi-detector row CT between July 2001 and August 2004 and also underwent echocardiography. Aortic valve calcification at multi-detector row CT was visually graded on a scale ranging from 0 to 4 (0 = no calcification, 4 = severe calcification). CT findings were correlated with hemodynamic data obtained at echocardiography. Patients without aortic stenosis were compared with patients with aortic stenosis. The Student t test, Spearman correlation coefficient, chi(2) analysis, and an unweighted kappa test were used to compare results. RESULTS: Aortic valve calcification was noted on multi-detector row CT scans in 72 of the 402 patients (18%). Twelve of 20 patients (60%) with grade 3 or grade 4 calcification on CT scans had aortic stenosis at echocardiography, compared with only nine of 382 patients (2.4%) with grade 0-2 calcification (P < .001). Significant correlations were observed between the grade of aortic valve calcification and the echocardiographically determined mean (r = 0.45, P = .03) and peak transvalvular gradient (r = 0.47, P = .03). There was substantial agreement between the grade of valve calcification at multi-detector row CT and the severity of aortic valve disease at echocardiography (kappa = 0.67). CONCLUSION: Aortic valve calcification was an incidental finding on 18% of multi-detector row CT scans. The grade of aortic valve calcification is correlated with the hemodynamic severity of aortic valve disease as determined with echocardiography.

Aortic valve calcification as a marker for aortic stenosis severity: assessment on 16-MDCT.

OBJECTIVE: The degree of valvular calcification in patients with aortic stenosis was determined with retrospectively ECG-gated 16-MDCT and correlated with the severity of stenosis assessed at cardiac catheterization. SUBJECTS AND METHODS: We conducted a prospective study of 72 patients (38 men and 34 women; mean age +/- SD, 69.5 +/- 8.8 years) with aortic stenosis who underwent 16-MDCT and cardiac catheterization. Aortic valve calcification was assessed using the aortic Agatston score, aortic mass score, and aortic volume score. Severity of aortic stenosis was classified at cardiac catheterization. Aortic valve area and peak-to-peak and mean transvalvular gradients were correlated with the degree of calcification determined on MDCT. RESULTS: All measured aortic valve calcification scores were significantly higher in patients with severe aortic stenosis (n = 46) than in patients with moderate (n = 15) or mild (n = 11, p < 0.001) aortic stenosis. Aortic valve calcification scores were inversely related to aortic valve area (r = -0.67, p < 0.001 for aortic mass score) and correlated significantly with peak-to-peak (r = 0.70, p < 0.001) and mean transvalvular (r = 0.72, p < 0.001) gradients. No correlation between the aortic valve calcification and the total coronary calcium scores was observed. CONCLUSION: Aortic valve calcification assessed on 16-MDCT is associated with severity of aortic stenosis. Thus, aortic valve calcification scores should be calculated routinely in all patients undergoing MDCT for assessment of coronary calcification. High aortic valve calcification scores indicate possibly severe aortic stenosis and should prompt a further functional evaluation.