Epicardial adipose tissue in long-term hemodialysis patients: its association with vascular calcification and long-term development.

BACKGROUND: Epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD) in the general population. EAT is suggested to promote CAD by paracrine mechanisms and local inflammation. We evaluated whether in chronic hemodialysis (HD) patients EAT associates with CAD, how the amount of EAT develops over time, and if EAT independently predicts the mortality risk. METHODS: Post-hoc analysis of a prospective study in 59 chronic HD patients who underwent non-enhanced multi-slice computed tomography (MSCT) at baseline. Thirty-seven patients underwent another MSCT after 24 ± 5 months. We measured EAT volume (cm³) and Agatston calcification scores of coronary arteries (CAC) and aortic valves (AVC). All-cause mortality was assessed after a follow-up of 88 months (IQR 52-105). RESULTS: Baseline EAT was 128.2 ± 60.8 cm³ and significantly higher than in a control group of non-renal patients (94 ± 46 cm³; p < 0.05). Median Agatston score for CAC was 329 (IQR 23-1181) and for AVC was 0 (IQR 0-25.3) in HD patients. We observed significant positive correlations between baseline EAT and age (r = 0.386; p = 0.003), BMI (r = 0.314; p = 0.016), CAC (r = 0.278; p = 0.03), and AVC (r = 0.282; p = 0.03). In multivariate analysis, age, BMI and AVC remained as significant predictors of EAT (p < 0.01). Calcification scores significantly increased over 2 years; in contrast EAT change was not significant (+11 %, IQR -10 to 24 %; p = 0.066). The limited patient number in the present study precludes analysis of the EAT impact upon survival. CONCLUSION: EAT correlated significantly with cardiovascular calcification in long-term HD patients. Mean EAT did not significantly change over 2 years.

Prevention of vasculopathy by vitamin K supplementation: can we turn fiction into fact?

With the discovery that vitamin K-dependent matrix Gla-protein (MGP) is a strong and modifiable factor in the prevention of arterial calcification, vitamin K was put forward as novel treatment option in cardiovascular disease. The vasculoprotective properties of vitamin K are in part based on the ability to improve gamma-glutamylcarboxylation of MGP, which is a prerequisite for MGP as a calcification inhibitor. Data from experimental animal models reveal that high intake of vitamin K can prevent and even reverse vascular calcifications. In addition, clinical data demonstrate that prescription of vitamin K antagonists for long-term oral anticoagulant therapy accelerates vascular calcification. However, controlled data from randomized prospective vitamin K interventional trials are lacking, thereby weakening a general recommendation for supplementation. The present article summarizes our current knowledge on the association between vitamin K and cardiovascular health. Additionally, we focus on an outlook on important ongoing prospective vitamin K intervention studies. These studies address the issues whether vitamin K substitution helps modifying relevant cardiovascular surrogates such as vascular calcification and whether non-vitamin K oral anticoagulants provide an alternative to support cardiovascular health benefits. So research about cardiovascular protection by vitamin K is an evolving field in which we expect a boost of novel and relevant evidence shortly.

Regional left ventricular function after transapical vs. transfemoral transcatheter aortic valve implantation analysed by cardiac magnetic resonance feature tracking.

AIMS: This study analysed the impact of transapical (TA) vs. transfemoral (TF) access site transcatheter aortic valve implantation (TAVI) on post-procedural regional left ventricular (LV) function using cardiac magnetic resonance (CMR) feature tracking (FT). METHODS AND RESULTS: CMR was performed 3 months after TAVI on 44 consecutive patients with normal LV ejection fraction prior to TAVI. Twenty patients had TA-TAVI, and 24 had TF-TAVI. Standard cine imaging was performed in three standard cardiac long-axis views (two-, four- and three-chamber views). Myocardial peak systolic radial strain (PSRS) and peak systolic longitudinal strain (PSLS) were analysed based on CMR-FT considering 49 segments in each of the three views. There were no differences in PSRS and PSLS for the basal and mid-ventricular segments between TA- and TF-TAVI groups. In contrast, PSRS and PSLS of apical segments and apical cap were reduced in the TA- compared with the TF-TAVI group (PSRS: 15.7 ± 6.4 vs. 35.9 ± 15.7%, respectively, P < 0.001; PSLS: -8.9 ± 5.3 vs. -16.9 ± 4.3%, respectively, P < 0.001). Comparison of all non-apical segments vs. apical segments and apical cap demonstrated no difference in the TF group (PSRS: 34.6 ± 9.0 vs. 35.9 ± 15.7%; respectively, P = 0.702; PSLS: -17.8 ± 4.6 vs. -16.9 ± 4.3%; respectively, P = 0.802). After TA-TAVI, PSRS and PSLS of the apical segments were reduced compared with the non-apical segments (PSRS: 15.7 ± 6.4 vs. 33.5 ± 7.0%, respectively, P < 0.001; PSLS: -8.9 ± 5.3 vs. -15.5 ± 3.5%, respectively, P < 0.001). CONCLUSION: Apical LV function abnormalities can be detected at 3-month follow-up in all TA-TAVI patients using CMR-FT. TA-TAVI results in significant impairment of apical LV function compared with TF-TAVI.

Myocardial deformation imaging by two-dimensional speckle-tracking echocardiography for prediction of global and segmental functional changes after acute myocardial infarction: a comparison with late gadolinium enhancement cardiac magnetic resonance.

BACKGROUND: Myocardial deformation analysis by speckle-tracking echocardiography (STE) has been shown to accurately predict viability in patients with chronic ischemic left ventricular (LV) dysfunction. The aim of this study was to evaluate two-dimensional STE for the prediction of global and segmental LV functional changes after acute myocardial infarction (AMI) in comparison with late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR). METHODS: In 93 patients (mean age, 60 ± 11 years) with first AMIs (55 with ST-segment elevation myocardial infarctions and 38 with non-ST-segment elevation myocardial infarctions) treated with acute percutaneous coronary intervention, global peak longitudinal strain was determined to describe global function by STE, and peak systolic circumferential and longitudinal strain was determined for segmental function analysis. LGE CMR was performed to define the amounts of global and segmental myocardial scar. STE and LGE CMR were performed within 48 hours of AMI. At 6-month follow-up, transthoracic echocardiography was repeated to determine global und segmental LV recovery and adverse LV remodeling (increase in end-systolic volume > 15%). RESULTS: Accuracy to predict global functional improvement as well as LV remodeling at 6-month follow-up after AMI was similar for STE and LGE CMR (areas under the curve, 0.715 vs 0.729 [P = .8830] and 0.806 vs 0.824 [P = .7141], respectively). Peak systolic circumferential strain < -14.2% had sensitivity of 71.6% and specificity of 58.1% to predict segmental functional improvement. Compared with LGE CMR, the predictive accuracy of transmural STE for segmental functional improvement at 6-month follow-up was lower (area under the curve, 0.788 vs 0.668; P = .0001). Predictive accuracy for segmental functional improvement could be improved by analysis of endocardial circumferential strain (area under the curve, 0.700 vs 0.668 for transmural speckle-tracking echocardiographic analysis; P = .0023). CONCLUSIONS: Two-dimensional STE allows the prediction of global functional recovery as well as LV remodeling after AMI with accuracy comparable with that of LGE CMR. Accuracy to predict segmental functional recovery using transmural deformation analysis by two-dimensional STE is inferior compared with LGE CMR but can be improved by a layer-specific analysis of endocardial deformation.

Sclerostin as a potential novel biomarker for aortic valve calcification: an in-vivo and ex-vivo study.

BACKGROUND AND AIM OF THE STUDY: Sclerostin is a key negative regulator of bone formation. It was hypothesized that sclerostin might also play a potential role in the development of aortic valve calcification (AVC). The study aim was to evaluate serum sclerostin levels in patients with different degrees of AVC compared to a healthy control group, and to investigate local sclerostin expression in explanted calcified and non-calcified aortic valves. METHODS: A prospective cross-sectional study was performed in 115 patients (mean age 74 +/- 7 years) with echocardiographically proven AVC. Sclerostin serum levels were measured using ELISA and compared to values obtained from a healthy control population. For quantification of AVC, all patients of the study cohort underwent non-contrast-enhanced dual-source computed tomography (DSCT). Immunohistochemistry (IHC) staining for sclerostin and mRNA sclerostin expression was analyzed in 10 calcified aortic valves and 10 non-calcified age-matched control valves. RESULTS: Patients with AVC showed significantly higher sclerostin serum levels as compared to healthy controls (0.94 +/- 0.45 versus 0.58 +/- 0.26 ng/ml, p < 0.001). A significant correlation between sclerostin serum levels and Agatston AVC scores as assessed by DSCT was observed (r = 0.62, p < 0.001) in the study cohort. IHC revealed positive sclerostin staining in nine calcified valves, in contrast to negative staining for sclerostin in all non-calcified valves. Quantitative real-time PCR confirmed the increased sclerostin expression on mRNA level, with a significant up-regulation of sclerostin mRNA (fold change 150 +/- 52, p < 0.001) expression being shown in calcified aortic valves compared to non-calcified control valves. Co-staining experiments revealed that sclerostin-expressing cells co-express the major osteogenic transcription factor Runx2 and the extracellular matrix protein osteocalcin. CONCLUSION: Patients with AVC showed increased sclerostin serum levels compared to a healthy reference population, and it was revealed that the severity of AVC may be linked to increased sclerostin serum levels. Moreover, the PCR and staining data demonstrated an increased sclerostin expression in parallel to prototypic markers of osteogenic transdifferentiation, indicating a role of sclerostin in the valvular calcification process.

Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study.

BACKGROUND: Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover. Here, we assessed the potential association of sclerostin with the development of coronary artery (CAC) and aortic valve calcifications (AVC) in haemodialysis (HD) patients. METHODS: We conducted a cross-sectional multi-slice computed tomography (MS-CT) scanning study in 67 chronic HD patients (59.4 ± 14.8 yrs) for measurement of CAC and AVC. We tested established biomarkers as well as serum sclerostin (ELISA) regarding their association to the presence of calcification. Fifty-four adults without relevant renal disease served as controls for serum sclerostin levels. Additionally, sclerostin expression in explanted aortic valves from 15 dialysis patients was analysed ex vivo by immunohistochemistry and mRNA quantification (Qt-RT-PCR). RESULTS: CAC (Agatston score > 100) and any AVC were present in 65% and in 40% of the MS-CT patient group, respectively. Serum sclerostin levels (1.53 ± 0.81 vs 0.76 ± 0.31 ng/mL, p < 0.001) were significantly elevated in HD compared to controls and more so in HD patients with AVC versus those without AVC (1.78 ± 0.84 vs 1.35 ± 0.73 ng/mL, p = 0.02). Multivariable regression analysis for AVC revealed significant associations with higher serum sclerostin. Ex vivo analysis of uraemic calcified aortic valves (n = 10) revealed a strong sclerostin expression very close to calcified regions (no sclerostin staining in non-calcified valves). Correspondingly, we observed a highly significant upregulation of sclerostin mRNA in calcified valves compared to non-calcified control valves. CONCLUSION: We found a strong association of sclerostin with calcifying aortic heart valve disease in haemodialysis patients. Sclerostin is locally produced in aortic valve tissue adjacent to areas of calcification.

Impact of aortic valve calcification severity and impaired left ventricular function on 3-year results of patients undergoing transcatheter aortic valve replacement.

OBJECTIVES: To evaluate clinical pre-interventional predictors of 3-year outcome and mortality in high-risk patients with severe aortic valve stenosis treated with transcatheter aortic valve implantation (TAVI). METHODS: Among 367 patients included in the Aachen TAVI registry, 76 patients with baseline dual-source computed tomography (DSCT) for the quantification of aortic valve calcification (AVC) and a 3-year follow-up were identified. RESULTS: Survival at 30 days was 91 %, and it was 75 %, 66 % and 64 % at 1, 2 years and 3 years, respectively. Non-survivors at 3 years showed a significantly higher Agatston AVC score (2,854 ± 1,651) than survivors (1,854 ± 961, P = 0.007). Multivariate analysis including age, logistic EuroScore, glomerular filtration rate, Agatston AVC score, ejection fraction < 40 %, NYHA class, baseline medication, chronic lung disease and aortic regurgitation revealed that only the Agatston AVC score (P = 0.03) and impaired left ventricular function (P = 0.001) was significantly associated with mortality. Patients with Agatston AVC scores >2,000 had a significantly lower 3-year survival rate compared with patients with scores <2,000 (47 % vs 79 %, P = 0.004). CONCLUSIONS: In patients referred for TAVI, aortic valve calcification severity and impaired left ventricular function may serve as a predictor of long-term mortality. Therefore, AVC scores easily determined from pre-procedural CT datasets may be used for patient risk stratification.

Layer-specific strain-encoded MRI for the evaluation of left ventricular function and infarct transmurality in patients with chronic coronary artery disease.

BACKGROUND: The study aimed to evaluate whether layer-specific myocardial deformation imaging performed by strain-encoded imaging (SENC) allows quantification of regional left ventricular function and is related to scar transmurality defined by contrast-enhanced magnetic resonance imaging (ceMRI) in patients with chronic coronary artery disease (CAD). METHODS: 50 patients (mean age 62 ± 10 years) with CAD underwent ceMRI. Regional myocardial function was evaluated semi-quantitatively from steady-state free-precession cine sequences. Layer-specific peak circumferential strain was measured from long-axis views and peak longitudinal strain was evaluated from short-axis views in a 16-segment model. The extent of myocardial infarction was determined semiautomatically for each segment as relative amount of hyperenhancement by ceMRI. Wall motion and the degree of hyperenhancement were related to layer-specific myocardial strain. RESULTS: A total of 589 of 600 segments (98%) were analysed. Endocardial and epicardial circumferential as well as longitudinal strain showed significant differences between visually defined segmental function states and differed also significantly between the degree of infarct transmurality (all p<0.001). A cutoff peak circumferential endocardial strain value of -15% differentiated nontransmural from transmural infarcted myocardium with a sensitivity of 100% and a specificity of 86% (area under the curve (AUC) 0.94). Distinction of nontransmural infarcted myocardium from transmural infarcted myocardium was done more accurately using circumferential endocardial strain compared to longitudinal endocardial strain (AUC 0.94 vs. AUC 0.76, p=0.003). CONCLUSIONS: Quantitative analysis of segmental deformation by layer-specific SENC allows accurate discrimination between different transmurality states of myocardial infarction in patients with chronic CAD. Circumferential endocardial strain showed the best distinction between the different degrees of infarct transmurality.

Layer-specific analysis of myocardial deformation for assessment of infarct transmurality: comparison of strain-encoded cardiovascular magnetic resonance with 2D speckle tracking echocardiography.

AIMS: Separate analysis of endocardial and epicardial myocardial layer deformation has become possible using strain-encoded cardiovascular magnetic resonance (SENC) and 2D-dimensional speckle tracking echocardiography (Echo). This study evaluated and compared both modalities for the assessment of infarct transmurality as defined by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). METHODS AND RESULTS: In 29 patients (age 62.4 ± 11.7 years, 23 male) with ischaemic cardiomyopathy, SENC using 1.5 T CMR and Echo were performed. Peak circumferential systolic strain of the endocardial and the epicardial layer of 304 myocardial segments was assessed by SENC and by Echo. The segmental transmurality of myocardial infarction was determined as relative amount of LGE (0%: no infarction; 1-50%: non-transmural infarction; 51-100%: transmural infarction). Endocardial and epicardial strain defined by SENC and by Echo differed significantly between segments of different infarct transmurality determined by CMR. Endocardial layer circumferential strain analysis by Echo and by SENC allowed distinction of segments with non-transmural infarction from non-infarcted segments with similar accuracy [area under the curve (AUC) 0.699 vs. 0.649, respectively, P = 0.239]. Epicardial layer circumferential strain analysis by Echo and by SENC allowed distinction of transmural from non-transmural myocardial infarction defined by LGE CMR with similar accuracy (AUC 0.721 vs. 0.664, respectively, P = 0.401). Endocardial strain by SENC correlated moderately with endocardial strain by Echo (r = 0.50; standard error of estimate = 5.2%). CONCLUSION: Layer-specific analysis of myocardial deformation by Echo and by SENC allows discrimination between different transmurality categories of myocardial infarction with similar accuracy. However, accuracy of both methods is non-optimal, indicating that further tools for improvement should be evaluated in the future.

Quantitative analysis of endocardial and epicardial left ventricular myocardial deformation-comparison of strain-encoded cardiac magnetic resonance imaging with two-dimensional speckle-tracking echocardiography.

BACKGROUND: Quantitative analysis of segmental myocardial deformation of different myocardial layers has become possible using strain-encoded cardiac magnetic resonance imaging (SENC) and speckle-tracking echocardiography (STE). We evaluated and compared the quantitative analysis of myocardial deformation using SENC and STE. METHODS: In 44 patients (age 61 ± 13 years, 34 men), SENC by cardiac magnetic resonance imaging using a 1.5-Tesla whole-body scanner and two-dimensional STE were performed prospectively. Quantitative layer-specific analysis of segmental left ventricular function was performed to determine the peak circumferential and peak longitudinal systolic strain values using SENC and STE of an endocardial and epicardial myocardial layer. In addition, segmental function was defined as normokinetic, hypokinetic, or akinetic by visual analysis of the magnetic resonance imaging cine sequences. RESULTS: The endocardial and epicardial strain defined by SENC or STE differed significantly between the visually defined segmental function states. The correlation of the peak circumferential endocardial strain by SENC versus STE (intraclass correlation coefficient [ICC] 0.493, 95% CI 0.358-0.597) tended to be better than the correlation of the circumferential epicardial strain using both methods (ICC 0.321, 95% CI 0.238-0.399). The correlation of the peak longitudinal endocardial strain by SENC and STE was similar (ICC 0.472, 95% CI 0.398-0.541), in contrast to the longitudinal epicardial strain analysis by both techniques (ICC 0.554, 95% CI 0.417-0.655). Circumferential strain analysis by STE allowed better distinction of the hypokinetic or akinetic segments from the normokinetic segments than did the circumferential strain analysis by SENC of the endocardial layer (area under the receiver operating characteristic curve [AUC ROC] 0.946 vs 0.884; P < .001) or epicardial layer (AUC ROC 0.884 vs 0.782; P < .001). Longitudinal strain analysis using STE and SENC of the endocardial layer (AUC ROC 0.851 vs 0.839; P = .5838) and epicardial layer (AUC ROC 0.849 vs 0.833; P = .4321) had similar diagnostic value for identifying the presence of hypokinetic and akinetic segments. CONCLUSIONS: Quantitative analysis of segmental deformation by SENC and STE allowed accurate distinction of myocardial segments with different functional states. Circumferential endocardial strain analysis by STE allowed the best distinction of segments with impaired function from the normokinetic segments.

Evaluation of aortic root for definition of prosthesis size by magnetic resonance imaging and cardiac computed tomography: implications for transcatheter aortic valve implantation.

BACKGROUND: This study sought to compare cardiac magnetic resonance imaging (CMR) with dual source computed tomography (DSCT) for analysis of aortic root dimensions prior to transcatheter aortic valve implantation (TAVI). In addition, the potential impact of CMR and DSCT measurements on TAVI strategy defined by 2D-transesophageal echocardiography (TEE) was evaluated. METHODS: Aortic root dimensions were measured using CMR and DSCT in 58 patients referred for evaluation of TAVI. The TAVI strategy (choice of prosthesis size and decision to implant) was based on 2D-TEE annulus measurements. RESULTS: CMR and DSCT aortic root measurements showed an overall good correlation (r=0.86, p<0.001 for coronal aortic annulus diameters). There was also a good correlation between TEE and CMR as well as between TEE and DSCT for measurement of sagittal aortic annulus diameters (r=0.69, p<0.001). However, annulus diameters assessed by TEE (22.1±2.3mm) were significantly smaller than coronal aortic annulus diameters assessed by CMR (23.4±1.8mm, p<0.001) or DSCT (23.6±1.8, p<0.001). Regarding TAVI strategy, the agreement between TEE and sagittal CMR (kappa=0.89) as well as sagittal DSCT measurements (kappa=0.87) was statistically perfect. However, decision based on coronal CMR- or MSCT measurements would have modified TAVI strategy as compared to a TEE based choice in a significant number of patients (22% to 24%). CONCLUSION: In patients referred for TAVI, CMR measurements of aortic root dimensions show a good correlation with DSCT measurements and thus CMR may be an alternative 3D-imaging modality. Aortic annulus measurements using TEE, CMR and DSCT were close but not identical and the method used has important potential implications on TAVI strategy.

Aortic valve calcifications on chest films: how much calcium do I need?

OBJECTIVE: Aortic valve calcifications (AVC) as seen on conventional chest films or on CT are associated with aortic valve stenosis (AVS). The absence of AVC on chest films does not exclude high grade AVS. The aim of this study was to analyse if there is a threshold for the detection of AVC from conventional chest films in patients suffering from high grade AVS. METHODS AND RESULTS: The explanted aortic valves of 29 patients (16 male, mean age 72.3 +/- 11.5 years) with high grade AVS were examined by dual-source CT. AVC were quantified using the Agatston AVC score. In all patients conventional chest films obtained the day before surgery were evaluated for the presence of AVC. Results were analysed with students t-test, Spearman's rank correlation and ROC analysis. On conventional chest films AVC were visible in 18 patients. On CT all specimen presented with AVC with an Agatston AVC score ranging from 40.7 to 1870 (mean 991.3 +/- 463.1). In patients with AVC visible on chest films the AVC score was significantly higher (1264.0 +/- 318.2) when compared with patients without visible calcifications (544.9 +/- 274.4; P < 0.0001). There was a strong correlation between the AVC score and the visibility of AVC on chest films (r = 0.781). ROC analysis identified an ideal threshold of 718 for AVC score to separate conventional chest films with and without visible AVC. CONCLUSION: Unlike in coronary calcifications, there is a threshold for identifying AVC from conventional chest films. This finding may be of diagnostic value, as conventional chest films may be used to semiquantitatively evaluate the extent of AVC.

Comparison of two-dimensional and three-dimensional imaging techniques for measurement of aortic annulus diameters before transcatheter aortic valve implantation.

AIMS: Different two-dimensional (2D) and three-dimensional (3D) imaging techniques are used for procedure planning and selection of prosthesis size before transcatheter aortic valve implantation. This study sought to compare different 2D and 3D imaging techniques and determine the accuracy of 3D transoesophageal echocardiography (TEE) for accurate analysis of aortic annulus dimensions. METHODS: In 49 consecutive patients with severe aortic stenosis undergoing transcatheter aortic valve implantation angiography, 2D transthoracic echocardiography (TTE), 2D and 3D TEE, and dual-source CT (DSCT) were performed to determine aortic annulus diameters. TTE and 2D TEE provided only one diameter of the aortic annulus. Angiography, DSCT and 3D TEE allowed measurement of diameters in sagittal and coronal views. The distance between aortic annulus and left main coronary artery ostium was measured by angiography, DSCT and 3D TEE. RESULTS: Sagittal diameters determined by angiography, TTE, 2D TEE, 3D TEE and DSCT were smaller than coronal diameters determined by angiography, 3D TEE and DSCT. Coronal and sagittal diameters determined by 3D TEE were in high agreement with corresponding measurements by DSCT (23.60±1.89 vs 23.46±2.07 mm and 22.19±1.96 vs 22.27±2.01 mm, respectively; mean±SD). There was a high correlation between DSCT and 3D TEE for the definition of coronal and sagittal aortic annulus diameters (r=0.88, SEE=0.89 mm and r=0.77, SEE=1.26 mm, respectively). Correlation of 3D TEE (13.47±1.67 mm) and DSCT (13.64±1.82 mm) in the analysis of the distance between aortic annulus and left main coronary artery ostium was better (r=0.54, SEE=1.55 mm) than between angiography (14.85±3.84 mm) and DSCT (r=0.35, SEE=1.77 mm). CONCLUSIONS: 3D imaging techniques should be used to evaluate aortic annulus diameters, as 2D imaging techniques, providing only a sagittal view, underestimate them. 3D TEE provides measurements of aortic annulus diameters similar to those obtained by DSCT.

Electrocardiographic and imaging predictors for permanent pacemaker requirement after transcatheter aortic valve implantation.

BACKGROUND AND AIM OF THE STUDY: Pacemaker (PM) implantation is a possible requirement after transcatheter aortic valve implantation (TAVI). The study aim was to evaluate the electrocardiographic and imaging predictors of the need for PM implantation after TAVI. METHODS: A total of 80 consecutive patients (mean age 82 +/- 6 years) who had been referred for TAVI were included in the study. Transfemoral TAVI was performed in 58 patients (CoreValve ReValving; 72%), while 22 patients (28%) underwent transapical TAVI using the Edwards SAPIEN valve. Patient characteristics, and the frequency of atrioventricular (AV) block, right bundle branch block (RBBB) and left bundle branch block (LBBB), were evaluated for the prediction of PM implantation after TAVI. In addition, the severity and distribution of aortic valve calcification (AVC) were assessed by calculating the Agatston AVC score for the total aortic valve, as well as for each cusp, using dual-source computed tomography. RESULTS: Pre-procedural RBBB was present in six patients (8%), while eight patients (10%) showed pre-procedural LBBB. In 20 of the 80 patients (25%), a new LBBB was observed after TAVI. In 17 TAVI patients (21%; only CoreValve patients) there was an indication for permanent PM implantation that was related to complete AV block (n = 13) or complete RBBB or LBBB with AV delay (n = 4). Four of six patients (67%) with pre-procedural RBBB received a PM after TAVI. Multivariate logistic regression analysis revealed that only prosthesis type (r = 0.30, p = 0.01) and pre-procedural RBBB (r = 0.4, p = 0.02) were significantly associated with the need for permanent PM implantation after TAVI. CONCLUSION: TAVI is frequently associated with new conduction disturbances. A higher incidence of new LBBB and of permanent PM requirement occurred with the CoreValve ReValving system. There was no relationship between the severity or distribution of AVC and the need for PM implantation after TAVI. Patients with pre-procedural RBBB are deemed to be at risk for PM implantation after TAVI.

Layer-specific analysis of myocardial function for accurate prediction of reversible ischaemic dysfunction in intermediate viability defined by contrast-enhanced MRI.

BACKGROUND: Contrast-enhanced MRI (ceMRI) has impaired accuracy in the prediction of functional recovery after revascularisation in cases of intermediate myocardial viability. OBJECTIVE: To evaluate the predictive value of layer-specific myocardial deformation analysis for improvement in ischaemic dysfunction after revascularisation. METHODS: In 132 patients with ischaemic left ventricular dysfunction undergoing revascularisation, myocardial viability was assessed by pixel-tracking-derived myocardial deformation imaging and ceMRI. Peak systolic circumferential strain was determined for total wall thickness and for three myocardial layers (endocardial, mid-myocardial and epicardial) in a 16-segment model. Analysis to predict recovery of function at 8±2 months after revascularisation was performed considering all dysfunctional segments or only segments with intermediate viability by ceMRI (hyperenhancement 25-75%, N=735 segments). RESULTS: Segments with functional recovery (N=568) had higher circumferential strain in all myocardial layers and a smaller degree of hyperenhancement than segments without functional recovery (N=433). Analysis of all dysfunctional segments showed that the predictive accuracy for functional recovery was high for endocardial strain, total wall thickness strain and hyperenhancement by ceMRI (area under the curve (AUC) 0.883, 0.782 and 0.834, respectively). Considering only segments with intermediate viability by ceMRI, endocardial circumferential strain allowed prediction of functional recovery with higher accuracy (specificity 75%, sensitivity 78%, AUC=0.811, 95% CI 0.776 to 0.851) than hyperenhancement analysis (specificity 59%, sensitivity 72%, AUC=0.705, 95% CI 0.659 to 0.747, p<0.05). CONCLUSION: Analysis of layer-specific myocardial function using deformation imaging allows accurate identification of reversible myocardial dysfunction. In segments with intermediate viability analysis of layer-specific deformation may have special advantages for prediction of functional recovery.

Functional cardiac MR imaging with true fast imaging with steady-state free precession before and after intravenous injection of contrast medium: comparison of image quality and accuracy.

OBJECTIVE: To compare image quality and accuracy of left ventricular function of cine SSFP (steady-state free precession) images before and after injection of Gd-DTPA. METHODS: In 30 patients T1 times of LV blood and myocardium were measured before and after injection of 0.2 mmol/kg body weight Gd-DTPA. Signal intensity of myocardium and left ventricular blood were measured on SSFP images and the contrast calculated. In 20 additional patients short axis images completely covering the left ventricle were acquired before and after injection of Gd-DTPA and parameters of left ventricular function compared. Image quality and regional function were assessed using the 17-segment model. RESULTS: Image quality after injection of contrast medium did not significantly change compared with unenhanced images. Contrast between myocardium and LV blood decreased from 0.6 ± 0.01 to 0.4 ± 0.03 after injection while the T1 value of myocardium decreased from 1121 ± 21 ms to 389 ± 14 ms (blood 1413 ± 48 ms to 222 ± 8 ms). Assessment of regional and global left ventricular function revealed similar results before and after the injection of contrast medium. CONCLUSION: Cine SSFP can be obtained after injection of contrast medium without loss of accuracy for regional and global LV ventricular function. This protocol can be used to decrease imaging time for thorough cardiac examination.

Association of aortic valve calcification severity with the degree of aortic regurgitation after transcatheter aortic valve implantation.

BACKGROUND: This study sought to examine a possible relationship between the severity of aortic valve calcification (AVC), the distribution of AVC and the degree of aortic valve regurgitation (AR) after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS). METHODS: 57 patients (22 men, 81 ± 5 years) with symptomatic AS and with a logistic EuroSCORE of 24 ± 12 were included. 38 patients (67%) received a third (18F)-generation CoreValve® aortic valve prosthesis, in 19 patients (33%) an Edwards SAPIEN™ prosthesis was implanted. Prior to TAVI dual-source computed tomography for assessment of AVC was performed. To determine the distribution of AVC the percentage of the calcium load of the most severely calcified cusp was calculated. After TAVI the degree of AR was determined by angiography and echocardiography. The severity of AR after TAVI was related to the severity and distribution of AVC. RESULTS: There was no association between the distribution of AVC and the degree of paravalvular AR after TAVI as assessed by angiography (r = -0.02, p = 0.88). Agatston AVC scores were significantly higher in patients with AR grade ≥ 3 (5055 ± 1753, n = 3) than in patients with AR grade < 3 (1723 ± 967, p = 0.03, n = 54). Agatston AVC scores > 3000 were associated with a relevant paravalvular AR and showed a trend for increased need for second manoeuvres. There was a significant correlation between the severity of AVC and the degree of AR after AVR (r = 0.50, p < 0.001). CONCLUSION: Patients with severe AVC have an increased risk for a relevant AR after TAVI as well as a trend for increased need for additional procedures.

Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species.

Matrix γ-carboxyglutamate (Gla) protein (MGP) is an important local inhibitor of vascular calcification, which can undergo two post-translational modifications: vitamin K-dependent γ-glutamate carboxylation and serine phosphorylation. While carboxylation is thought to have effects upon binding of calcium-ions, phosphorylation is supposed to affect the cellular release of MGP. Since both modifications can be exerted incompletely, various MGP species can be detected in the circulation. MGP levels were measured with two commercially available competitive and two novel sandwich assays in healthy controls, in patients with rheumatic disease, aortic valve disease, and end-stage renal disease, as well as in volunteers after vitamin K supplementation (VKS) and treatment with vitamin K antagonists (VKA). Major differences were found between the MGP assays, including significantly different behaviour with regard to vascular disease and the response to VKA and VKS. The dual-antibody assay measuring non-phosphorylated, non-carboxylated MGP (dp-ucMGP) was particularly sensitive for these changes and would be suited to assess the vascular vitamin K status. We conclude that the different assays for particular circulating MGP species allows the assessment of various aspects of the MGP system.

Long-term clinical outcome of sirolimus-eluting stent implantation in metabolic syndrome and diabetes.

BACKGROUND: Patients with metabolic syndrome (MetS) are at increased risk of cardiovascular events. The long-term effectiveness of sirolimus-eluting stents (SES) in patients with MetS and in diabetic patients is not well defined. METHODS: 563 consecutive patients with 629 de novo coronary lesions (< 50 mm lesion length, reference diameter < 3.5 mm) successfully treated with SES were enrolled in the study and followed for 41 +/- 17 months. Bifurcation and left main lesions were excluded. Patients were categorized into three groups: 1) no MetS and no diabetes; 2) MetS and no diabetes; and 3) diabetes. MetS was defined as the presence of > or = 3 of the following criteria: obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, elevated fasting glucose. RESULTS: 284 patients (51%) with 318 lesions had neither MetS nor diabetes, 148 patients (26%) with 163 lesions had MetS without diabetes and 131 patients (23%) with 148 lesions had diabetes. Baseline angiographic parameters were comparable between the three groups. Clinically driven target lesion revascularization rates for controls, MetS and diabetics were 7.7%, 5.4% and 14.5%, respectively (p = 0.041). Mortality rates for the three groups were 4.2%, 10.1% and 15.3%, respectively (p = 0.042). There were also significant differences in stent thrombosis (ST) rates with 0.3% in controls, 0.6% in MetS and 6.1% in diabetics (p = 0.037). Annual mortality and ST rates for controls, patients with MetS and diabetic patients were 1.2%, 3.0% and 5.6% (p = 0.037) and 0.2%, 0.3% and 2.7% (p = 0.039), respectively. Late loss in-lesion was 0.19 +/- 0.59 mm in controls, 0.17 +/- 0.44 mm in patients with MetS/no diabetes and 0.46 +/- 0.81 mm in diabetics (p < 0.001). CONCLUSION: During long-term follow up after implantation of SES in de novo coronary lesions, MetS without diabetes does not result in an increase in target lesion revascularization or ST rates compared with control patients. However, patients with MetS have a higher follow-up mortality rate compared to control patients.