Magnetic resonance myocardial perfusion imaging at 3.0 Tesla for the identification of myocardial ischaemia: comparison with coronary catheter angiography and fractional flow reserve measurements.

AIMS: To assess image quality and diagnostic performance of 3.0 Tesla (3T) cardiac magnetic resonance (CMR) myocardial perfusion imaging with a dual radiofrequency source to detect functional relevant coronary artery disease (CAD), using coronary angiography and invasive pressure-derived fractional flow reserve (FFR) as reference standard. METHODS AND RESULTS: We included 116 patients with suspected or known CAD, who underwent 3T adenosine myocardial perfusion CMR (resolution 2.97 × 2.97 mm) and coronary angiography plus FFR measurements in intermediate lesions. Image quality of myocardial perfusion CMR was graded on a 4-point scale (1 = poor to 4 = excellent). Diagnostic accuracy was assessed by ROC analyses using a 16-myocardial segment-based summed perfusion score (0 = normal to 3 = transmural perfusion defect) and by determining sensitivity, specificity, positive and negative predictive value on the coronary vessel territory and the patient level. Diagnostic image quality was achieved for all stress myocardial perfusion CMR studies with an average quality score of 2.5, 3.1, and 3.0 for LAD, LCX, and RCA territories. The ability of the myocardial perfusion CMR perfusion score to detect significant coronary artery stenosis yielded an area under the curve of 0.93 on ROC analysis. Values for sensitivity, specificity, positive and negative predictive value on a vessel territory level and the patient level were 89, 95, 87, 96% and 85, 87, 77, 92%, respectively. CONCLUSION: In patients with suspected or known significant CAD, 3T myocardial perfusion CMR with standard perfusion protocols provides consistently high image quality and an excellent diagnostic performance.

Circulating concentrations of GLP-1 are associated with coronary atherosclerosis in humans.

BACKGROUND: GLP-1 is an incretine hormone which gets secreted from intestinal L-cells in response to nutritional stimuli leading to pancreatic insulin secretion and suppression of glucagon release. GLP-1 further inhibits gastric motility and reduces appetite which in conjunction improves postprandial glucose metabolism. Additional vasoprotective effects have been described for GLP-1 in experimental models. Despite these vasoprotective actions, associations between endogenous levels of GLP-1 and cardiovascular disease have yet not been investigated in humans which was the aim of the present study. METHODS: GLP-1 serum levels were assessed in a cohort of 303 patients receiving coronary CT-angiography due to typical or atypical chest pain. RESULTS: GLP-1 was found to be positively associated with total coronary plaque burden in a fully adjusted model containing age, sex, BMI, hypertension, diabetes mellitus, smoking, triglycerides, LDL-C (low density lipoprotein cholesterol), hsCRP (high-sensitive C-reactive protein), and eGFR (estimated glomerular filtration rate) (OR: 2.53 (95% CI: 1.12 - 6.08; p = 0.03). CONCLUSION: Circulating GLP-1 was found to be positivity associated with coronary atherosclerosis in humans. The clinical relevance of this observation needs further investigations.

Fully automated derivation of coronary artery calcium scores and cardiovascular risk assessment from contrast medium-enhanced coronary CT angiography studies.

OBJECTIVES: Performance evaluation of a fully automated system for calculating computed tomography (CT) coronary artery calcium scores from contrast medium-enhanced coronary CT angiography (cCTA) studies. METHODS: One hundred and twenty-seven patients (58 ± 11 years, 71 men) who had undergone cCTA as well as an unenhanced CT calcium scoring study where included. Calcium scores were computed from cCTA by an automated image processing algorithm and compared with calcium scores obtained by standard manual assessment of unenhanced CT calcium scoring studies. Results were compared vis-a-vis (1) absolute calcium score values, (2) age-, gender- and race-dependent percentiles, and (3) commonly used calcium score risk classification categories. RESULTS: One hundred and nineteen out of 127 (93.7%) studies were successfully processed. Mean Agatston calcium score values obtained by traditional non-contrast CT calcium scoring studies and derived from contrast medium-enhanced cCTA did not significantly differ (235.6 ± 430.5 vs 262.0 ± 499.5; P > 0.05). Calcium score risk categories and Multi-Ethnic Study of Atherosclerosis (MESA) percentiles showed very high correlation (Spearman rank correlation coefficient = 0.97, P < 0.0001/0.95, P < 0.0001) between the two approaches. CONCLUSIONS: Calcium score values automatically computed from cCTA are highly correlated with standard unenhanced CT calcium scoring studies. These results suggest a radiation dose- and time-saving potential when deriving calcium scores from cCTA studies without a preceding unenhanced CT calcium scoring study.

Aortic valve calcium score as a predictor for outcome after TAVI using the CoreValve revalving system.

BACKGROUND: TAVI is a novel treatment option for patients at too high risk for surgery. Risk scores for surgical valve replacement failed to accurately predict outcomes after TAVI and alternative risk parameters are lacking so far. OBJECTIVE: We evaluated the CT-derived aortic valve calcification score as a predictor for outcome during and after TAVI. METHODS: Transfemoral TAVI using the CoreValve device was performed in 68 patients, in whom the aortic valve calcium score was determined from preprocedural 64-sclice ECG gated CT-scans. RESULTS: 30-day MACE rate (death, stroke, MI) was 10.3%, 1-year mortality was 11.8%. Using linear regression analysis the aortic valve calcium score was the only significant predictor for 30-day MACE and for 1-year mortality and was also associated with the incidence and severity of post procedural aortic regurgitation (r=0.33, p<0.05). Patients withvalve calcium scores >750 had a significant lower 1-year survival rate compared to patients with scores <750 (58% vs. 98%, p<0.05). The aortic valve calcium score is also inversely associated with the absolute improvement of NYHA-class after TAVI (regression coefficient=-0.43, p<0.02). CONCLUSION: The degree of aortic valve calcification is associated with post procedural aortic regurgitation, procedural complications, 1-year mortality and with the degree of functional improvement of patients who underwent TAVI using the CoreValve device. Due to the fact that the aortic valve calcium score can be determined from CT-datasets that are used for preprocedural planning, this parameter may be incorporated in the general work up and may be used for risk stratification and patient selection.

CT evaluation of coronary artery stents with iterative image reconstruction: improvements in image quality and potential for radiation dose reduction.

OBJECTIVES: Comparison of coronary artery stent assessment with cardiac CT angiography (cCTA) using traditional filtered back projection (FBP) and sinogram affirmed iterative reconstruction (SAFIRE), in both full- and half-radiation dose image data. METHODS: Dual-source cCTA studies of 37 implanted stents were reconstructed at full- and half-radiation dose with FBP and SAFIRE. Half-dose data were based on projections from one DSCT detector. In-stent noise, signal-to-noise ratio (SNR), and stent-lumen attenuation increase ratio (SAIR) were measured and image quality graded. Stent volumes were measured to gauge severity of beam hardening artefacts. RESULTS: Full-dose SAFIRE reconstructions were superior to full-dose FBP vis-à-vis in-stent noise (21.2 ± 6.6 vs. 35.7 ± 17.5; P < 0.05), SNR (22.1 ± 8.6 vs. 14.3 ± 6.7; P < 0.05), SAIR (19.6 ± 17.6 vs. 33.4 ± 20.4%; P < 0.05), and image quality (4.2 ± 0.86 vs. 3.5 ± 1.0; P < 0.05). Stent volumes were lower measured with SAFIRE (119.9 ± 53.7 vs. 129.8 ± 65.0 mm(3); P > 0.05). Comparing half-dose SAFIRE with full-dose FBP, in-stent noise (26.7 ± 13.0 vs. 35.7 ± 17.5; P < 0.05) and SNR (18.2 ± 6.9 vs. 14.3 ± 6.7; P < 0.05) improved significantly. SAIR (31.6 ± 24.3 vs. 33.4 ± 20.4%; P > 0.05), stent volume (129.6 ± 57.3 vs. 129.8 ± 65.0 mm(3); P > 0.05), and image quality (3.5 ± 1.0 vs. 3.7 ± 1.1; P > 0.05) did not differ. Radiation dose decreased from 8.7 ± 5.2 to 4.3 ± 2.6 mSv. CONCLUSIONS: Iterative reconstruction significantly improves imaging of coronary artery stents by CT compared with FBP, even with half-radiation-dose data.

Cryoballoon in AF ablation: impact of PV ovality on AF recurrence.

INTRODUCTION: Complete occlusion of the pulmonary veins (PV) is crucial for successful PV isolation. While two different sizes of cryoballoons (23 and 28 mm) are available, complete occlusion is not always achieved in any given PV. We investigated the role of PV ostial anatomy during cryoballoon PV occlusion grading and atrial fibrillation (AF) recurrence rate. METHODS: PV ostial diameter was analyzed in 168 consecutive patients (111 men, 61 ± 10 years, 124 paroxysmal (px) and 44 persistent AF) using cardiac computed tomography (CT) prior to procedure. The ovality index at the PV ostial level was calculated in any given PV. During follow-up, 7-day holter monitors were performed at 1, 3, 6, 9, 12, 18 and 24 months post-ablation. RESULTS: The success rate at 12 ± 6 months follow-up was 69% including a 3-month blanking period (px AF: 66%; persistent AF 77%). The ovality index of the left-sided PVs was significantly larger ("more oval") than that of the right-sided PVs (p<0.001). An optimized PV occlusion in all individual PVs (complete occlusion, grading 4/4) was achieved during ablation in 49% of patients with AF recurrence and in 73% of patients without AF recurrence (p=0.004). Patients with AF recurrence had "more oval" left-sided PVs compared to patients free from AF recurrence (LSPV 0.40 ± 0.2 vs. 0.33 ± 0.2; p=0.04 and LIPV 0.41 ± 0.3 vs. 0.32 ± 0.2; p=0.03), whereas no significant association was found for right sided PVs. CONCLUSION: The ostial PV anatomy seems to have an important impact on clinical outcome and should be considered when planning and performing cryoballoon AF ablation procedures.

Lipoprotein (a) is independently correlated with coronary artery calcification.

INTRODUCTION: Lipoprotein a (Lp(a)) has been recognized as a risk factor for both coronary heart diseases and for cardiovascular events. Coronary artery calcification (CAC) is a well proven marker for coronary artery disease and risk factor for cardiovascular events. Still there are conflicting data regarding the relationship of Lp(a) and CAC. We therefore wanted to evaluate the influence of Lp(a) on CAC. METHODS: 1560 European patients (1123 men, age 59.3 ± 20.8 years) with typical or atypical chest pain underwent CAC scoring by a multi-slice CT-scanner, using a standard protocol. Blood samples were evaluated the same day using an automated particle enhanced immunoturbidimetric assay to determine Lp(a) serum levels. RESULTS: There was a positive correlation between CAC score, age, and common cardiovascular risk factors. Lp(a) serum levels were not associated with age but a positive correlation between Lp(a) serum levels and CAC was found. In the multivariate analysis age, diabetes, statin therapy, and Lp(a) could be identified as independent risk factors for CAC. (p<0.001). BMI, smoking, hypertension and LDL-C were not independently associated with CAC. CONCLUSION: Lp (a) could be identified as an independent predictor of CAC, a marker of coronary atherosclerosis. Further a positive correlation between increasing Lp (a) levels and CAC scores was found.

Accuracy of 64-multidetector computed tomography coronary angiography in patients with symptomatic atrial fibrillation prior to pulmonary vein isolation.

AIMS: Aim of our study was to investigate the value of multidetector computed tomography (MDCT) for detecting significant stenoses of coronary arteries in patients with symptomatic atrial fibrillation (AF) prior to pulmonary vein (PV) ablation (PVA). BACKGROUND: Many patients undergoing PVA for AF receive three-dimensional computed tomography or magnetic resonance tomography imaging for improving anatomical orientation. METHODS: One-hundred and eighty-one patients with AF refractory to antiarrhythmic treatment underwent ECG-gated 64-MDCT for identification of PV anatomy and simultaneous assessment of coronary vessels before PVA. No additional radiation was incurred for MDCT coronary angiography during MDCT scan. Pretest probability for obstructive coronary artery disease (CAD) was estimated. Invasive coronary angiography (ICA) was performed in all patients with at least intermediate risk of CAD. RESULTS: Eighty-six out of 181 patients (48%) had ICA and MDCT, 95 patients (52%) underwent MDCT alone. ICA revealed significant stenoses in 9% of the catheterized patients (8/86). MDCT investigation lead to a sensitivity of 90% (9/10), specificity of 98% (829/844 lesions), positive predictive value (PPV) of 39% (9/24), and negative predictive value (NPV) of 100% (829/830 lesions) for the detection of >50% stenoses seen on ICA. All patients with a significant stenosis were classified as patients with CAD. Overall prevalence of significant CAD detected by MDCT was found to be low with 10% of patients and 2% of all segments. CONCLUSION: MDCT coronary angiography is sensitive and highly specific in patients presenting for PVA. In this group a negative scan reliably excludes significant CAD. These data suggest that MDCT coronary angiography can replace ICA prior to PVA.

MMP-1 serum levels predict coronary atherosclerosis in humans.

BACKGROUND: Myocardial infarction results as a consequence of atherosclerotic plaque rupture, with plaque stability largely depending on the lesion forming extracellular matrix components. Lipid enriched non-calcified lesions are considered more instable and rupture prone than calcified lesions. Matrix metalloproteinases (MMPs) are extracellular matrix degrading enzymes with plaque destabilisating characteristics which have been implicated in atherogenesis. We therefore hypothesised MMP-1 and MMP-9 serum levels to be associated with non-calcified lesions as determined by CT-angiography in patients with coronary artery disease. METHODS: 260 patients with typical or atypical chest pain underwent dual-source multi-slice CT-angiography (0.6-mm collimation, 330-ms gantry rotation time) to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified. RESULTS: In multivariable regession analysis, MMP-1 serum levels were associated with total plaque burden (OR: 1.37 (CI: 1.02-1.85); p < 0.05) in a model adjusted for age, sex, BMI, classical cardiovascular risk factors, hsCRP, adiponectin, pericardial fat volume and medication. Specification of plaque morphology revealed significant association of MMP-1 serum levels with non-calcified plaques (OR: 1.16 (CI: 1.0-1.34); p = 0.05) and calcified plaques (OR: 1.22 (CI: 1,03-1.45); p < 0.05) while association with mixed plaques was lost in the fully adjusted model. No associations were found between MMP9 serum levels and total plaque burden or plaque morphology. CONCLUSION: MMP-1 serum levels are associated with total plaque burden but do not allow a specification of plaque morphology.

Chemerin is associated with markers of inflammation and components of the metabolic syndrome but does not predict coronary atherosclerosis.

OBJECTIVES: Chemerin is a recently discovered adipokine that regulates adipocyte differentiation and modulates chemotaxis and activation of dendritic cells and macrophages. Given the convergence of adipocyte and macrophage function, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis in humans. We sought to examine the relationship of i) chemerin and markers of inflammation, ii) chemerin and components of the metabolic syndrome, and iii) chemerin and coronary atherosclerotic plaque burden and morphology. DESIGN: Serum chemerin levels were determined in 303 patients with stable typical or atypical chest pain who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed, or non-calcified. RESULTS: Chemerin levels were highly correlated with high sensitivity C-reactive protein (r=0.44, P<0.0001), interleukin-6 (r=0.18, P=0.002), tumor necrosis factor-alpha (r=0.24, P<0.0001), resistin (r=0.28, P<0.0001), and leptin (r=0.36, P<0.0001) concentrations. Furthermore, chemerin was associated with components of the metabolic syndrome including body mass index (r=0.23, P=0.0002), triglycerides (r=0.29, P<0.0001), HDL-cholesterol (r=-0.18, P=0.003), and hypertension (P<0.0001). In bivariate analysis, chemerin levels were weakly correlated with coronary plaque burden (r=0.16, P=0.006) and the number of non-calcified plaques (r=0.14, P=0.02). These associations, however, were lost after adjusting for established cardiovascular risk factors (odds ratio, OR 1.17, 95% confidence interval (CI) 0.97-1.41, P=0.11 for coronary plaque burden; OR 1.06, 95% CI 0.96-1.17, P=0.22 for non-calcified plaques). CONCLUSIONS: Chemerin is strongly associated with markers of inflammation and components of the metabolic syndrome. However, chemerin does not predict coronary atherosclerosis.

Low adiponectin levels are an independent predictor of mixed and non-calcified coronary atherosclerotic plaques.

BACKGROUND: Atherosclerosis is the primary cause of coronary artery disease (CAD). There is increasing recognition that lesion composition rather than size determines the acute complications of atherosclerotic disease. Low serum adiponectin levels were reported to be associated with coronary artery disease and future incidence of acute coronary syndrome (ACS). The impact of adiponectin on lesion composition still remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: We measured serum adiponectin levels in 303 patients with stable typical or atypical chest pain, who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified. In bivariate analysis adiponectin levels were inversely correlated with total coronary plaque burden (r = -0.21, p = 0.0004), mixed (r = -0.20, p = 0.0007) and non-calcified plaques (r = -0.18, p = 0.003). No correlation was seen with calcified plaques (r = -0.05, p = 0.39). In a fully adjusted multivariate model adiponectin levels remained predictive of total plaque burden (estimate: -0.036, 95%CI: -0.052 to -0.020, p<0.0001), mixed (estimate: -0.087, 95%CI: -0.132 to -0.042, p = 0.0001) and non-calcified plaques (estimate: -0.076, 95%CI: -0.115 to -0.038, p = 0.0001). Adiponectin levels were not associated with calcified plaques (estimate: -0.021, 95% CI: -0.043 to -0.001, p = 0.06). Since the majority of coronary plaques was calcified, adiponectin levels account for only 3% of the variability in total plaque number. In contrast, adiponectin accounts for approximately 20% of the variability in mixed and non-calcified plaque burden. CONCLUSIONS/SIGNIFICANCE: Adiponectin levels predict mixed and non-calcified coronary atherosclerotic plaque burden. Low adiponectin levels may contribute to coronary plaque vulnerability and may thus play a role in the pathophysiology of ACS.

Predictive value of coronary calcifications for future cardiac events in asymptomatic patients with diabetes mellitus: a prospective study in 716 patients over 8 years.

BACKGROUND: To establish an efficient prophylaxis of coronary artery disease reliable risk stratification is crucial, especially in the high risk population of patients suffering from diabetes mellitus. This prospective study determined the predictive value of coronary calcifications for future cardiovascular events in asymptomatic patients with diabetes mellitus. METHODS: We included 716 patients suffering from diabetes mellitus (430 men, 286 women, age 55.2+/-15.2 years) in this study. On study entry all patients were asymptomatic and had no history of coronary artery disease. In addition, all patients showed no signs of coronary artery disease in ECG, stress ECG or echocardiography. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomograph. For quantification of coronary calcifications we calculated the Agatston score. After a mean observation period of 8.1+/-1.1 years patients were contacted and the event rate of cardiac death (CD) and myocardial infarction (MI) was determined. RESULTS: During the observation period 40 patients suffered from MI, 36 patients died from acute CD. The initial Agatston score in patients that suffered from MI or died from CD (475+/-208) was significantly higher compared to those without cardiac events (236+/-199, p<0.01). An Agatston score above 400 was associated with a significantly higher annualised event rate for cardiovascular events (5.6% versus 0.7%, p<0.01). No cardiac events were observed in patients with exclusion of coronary calcifications. Compared to the Framingham risk score and the UKPDS score the Agatston score showed a significantly higher diagnostic accuracy in the prediction of MI with an area under the ROC curve of 0.77 versus 0.68, and 0.71, respectively, p<0.01. CONCLUSION: By determination of coronary calcifications patients at risk for future MI and CD could be identified within an asymptomatic high risk group of patients suffering from diabetes mellitus. On the other hand future events could be excluded in patients without coronary calcifications.