Long-Term Outcomes After Treatment With a Paclitaxel-Coated Balloon Versus Balloon Angioplasty: Insights From the PEPCAD-DES Study (Treatment of Drug-eluting Stent [DES] In-Stent Restenosis With SeQuent Please Paclitaxel-Coated Percutaneous Transluminal Coronary Angioplasty [PTCA] Catheter).

OBJECTIVES: The intention this PEPCAD-DES (Treatment of Drug-eluting Stent [DES] In-Stent Restenosis With SeQuent Please Paclitaxel Eluting Percutaneous Transluminal Coronary Angioplasty [PTCA] Catheter) study update was to demonstrate the safety and efficacy of paclitaxel-coated balloon (PCB) angioplasty in patients with DES-ISR at 3 years. BACKGROUND: In the PEPCAD-DES trial late lumen loss and the need for repeat target lesion revascularization (TLR) was significantly reduced with PCB angioplasty compared with plain old balloon angioplasty (POBA) in patients with drug-eluting stent in-stent restenosis (DES-ISR) at 6 months. We evaluated whether the clinical benefit of reduced TLR and major adverse cardiac events (MACE) was maintained up to 3 years. METHODS: A total of 110 patients with DES-ISR in native coronary arteries with reference diameters ranging from 2.5 mm to 3.5 mm and lesion lengths ≤22 mm were randomized to treatment with either PCB or POBA in a multicenter, randomized, single-blind clinical study. With a 2:1 randomization, 72 patients were randomized to the PCB group and 38 patients to the POBA group. At baseline, there were lesions with at least 2 stent layers in PCB (52.8%, 38 of 72) and POBA (55.3%, 21 of 38) patients. RESULTS: At 36 months, the TLR rates were significantly lower in the PCB group compared with the POBA control group (19.4% vs. 36.8%; p = 0.046). Multiple TLRs in individual patients were more frequent in the POBA group compared with the PCB group (more than 1 TLR: POBA, 13.2%; PCB, 1.4%; p = 0.021). The 36-month MACE rate was significantly reduced in the PCB group compared with the POBA group (20.8% vs. 52.6%, log-rank p = 0.001). CONCLUSIONS: PCB angioplasty was superior to POBA for the treatment of DES-ISR patients in terms of MACE and TLR for up to 36 months. There was no late catch-up phenomenon. (Treatment of Drug-eluting Stent [DES] In-Stent Restenosis With SeQuent® Please Paclitaxel Eluting Percutaneous Transluminal Coronary Angioplasty [PTCA] Catheter [PEPCAD-DES]; NCT00998439).

Six-Year Prognostic Value of Microvascular Obstruction After Reperfused ST-Elevation Myocardial Infarction as Assessed by Contrast-Enhanced Cardiovascular Magnetic Resonance.

Although recent studies showed the prognostic value of cardiac magnetic resonance (CMR) parameters especially microvascular obstruction (MO) after reperfused ST-elevation myocardial infarction (STEMI), a study assessing their prognostic significance for long-term follow-up is missing so far. The objective of this study was to determine the prognostic impact of MO on long-term prognosis after reperfused first STEMI in a setting allocating CMR-assessed parameters to hard clinical events only. In 249 patients, CMR was performed after reperfused STEMI, and hereby, left ventricular ejection fraction (LVEF), infarct size (IS), and the amount of MO were quantified. Follow-up (median 6.0 years) was obtained regarding occurrence of major adverse cardiac events (MACE). MACE occurred more often in patients showing presence of MO (MO vs no MO: n = 61 [54%] vs n = 12 [9%], p <0.0001). By multivariate analysis, the extent of MO remained the strongest predictor (p <0.001) for occurrence of MACE and provided incremental prognostic value over clinical variables and LVEF (p = 0.028, c-index increase from 0.723 to 0.817). In conclusion, CMR-assessed MO proves predictive for assessment of 6-year prognosis in patients after reperfused first STEMI and provides incremental prognostic information over clinical variables and LVEF in a setting based on hard end points.

Accuracy of prospectively ECG-triggered very low-dose coronary dual-source CT angiography using iterative reconstruction for the detection of coronary artery stenosis: comparison with invasive catheterization.

OBJECTIVE: To evaluate the image quality and diagnostic accuracy of very low-dose computed tomography (CT) angiography (CTA) for the evaluation of coronary artery stenosis. BACKGROUND: Iterative reconstruction (IR) has shown to substantially reduce image noise and hence permit the use of very low-dose data acquisition protocols in coronary CTA. METHODS: Fifty symptomatic patients with an intermediate likelihood for coronary artery disease underwent coronary CTA (heart rate: 59 ± 5 bpm, prospectively ECG-triggered axial acquisition, 100 kV, 160 mAs, 2 × 128 × 0.6 mm collimation, 60 mL contrast, 6 mL/s) prior to invasive coronary angiography. CTA images were reconstructed using both standard filtered back projection (FBP) and a raw data-based IR algorithm [Sinogram Affirmed Iterative Reconstruction (SAFIRE), Siemens Healthcare]. Subjective image quality (four-point Likert scale from 0 = non-diagnostic to 3 = excellent image quality), image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), as well as the presence of coronary stenosis >50% were independently determined by two observers. RESULTS: The mean dose-length product was 46.8 ± 3.5 mGy cm (estimated effective dose 0.66 ± 0.05 mSv). IR led to significantly improved objective image quality compared with FBP (image noise: 41 ± 12 vs. 49 ± 11 HU, P < 0.0001; CNR: 16 ± 8 vs. 12 ± 4, P < 0.0001; SNR: 13 ± 7 vs. 10 ± 3, P < 0.0001). Four coronary segments were not evaluable on FBP data, whereas all segments showed diagnostic image quality with IR. To detect significant coronary stenosis, sensitivity, specificity, positive predictive value, and negative predictive value were 69% (11/16), 97% (175/180), 69% (11/16), and 97% (175/180) per vessel with FBP data sets, respectively. With IR data sets, the corresponding values were 81% (13/16), 97% (178/184), 68% (13/19), and 98% (178/181). These differences were not statistically significant (P = 0.617). CONCLUSIONS: Raw data-based IR significantly improves image quality in very low-dose prospectively ECG-triggered coronary dual-source CTA when compared with standard reconstruction using FBP.

Relation of functional echocardiographic parameters to infarct scar transmurality by magnetic resonance imaging.

BACKGROUND: Identification of viable but dysfunctional myocardium after myocardial infarction is important for management, including the decision for revascularization. Assessment of infarct transmurality (TRM) by late contrast enhancement on magnetic resonance imaging (MRI) is frequently used for this task but has several limitations, particularly its availability. The goal of this study was to compare the value of several simple echocardiographic parameters measured at rest at the bedside for the identification of three degrees of infarct TRM, with contrast-enhanced MRI as the gold standard. METHODS: In a prospective, single-center study, 41 patients (33 men; mean age, 62 ± 10 years; 32 with ST-segment elevation infarctions) underwent resting echocardiography and contrast-enhanced MRI <5 days after infarction. Wall motion score, preejection velocity by tissue Doppler, and longitudinal, circumferential, and radial peak systolic strain by speckle-tracking-based strain imaging were assessed, and the findings were compared with infarct TRM stratified by contrast-enhanced MRI (no scar, 0% TRM; nontransmural scar, 1%-50% TRM; and transmural scar, 51%-100% TRM). RESULTS: Four hundred segments showed no scar, 125 showed nontransmural scar, and 213 showed transmural scar on contrast-enhanced MRI. The sensitivity and specificity of visual wall motion scoring to detect any scar versus no scar were 71% and 81%, respectively, similar to values for circumferential strain (sensitivity and specificity both 81% with a cutoff of -14.5%). Longitudinal and radial strain performed less well, and the presence of preejection velocity performed distinctly worse (45% and 90%, respectively). The sensitivity and specificity for identifying nontransmural versus transmural infarction was better for circumferential strain (78% and 75%, respectively, with a cutoff of -10.5%) than for the other strain types, preejection velocity (52% and 67%, respectively), or visual wall motion scoring (50% and 81%, respectively, for a score > 2). CONCLUSION: Visual wall motion analysis alone is able to detect infarcted myocardium but cannot differentiate sufficiently between transmural and nontransmural infarction. This is best achieved at the bedside using speckle-tracking-based circumferential strain.

Anti-inflammatory effects of danshen on human vascular endothelial cells in culture.

Inflammation plays a crucial role in the pathophysiology of atherosclerosis. Besides cytokines, chemokines and cell adhesion molecules, CD40 and P-selectin play important roles as key regulators of the inflammatory process in atherosclerosis. Danshen (DS) is commonly used in traditional Chinese medicine for therapy of cardiovascular diseases such as coronary artery disease. The aim of the present study was to evaluate the protective effects of DS with respect to possible anti-inflammatory effects. Human umbilical vein endothelial cells as well as platelets were incubated with an extract of DS or one of its major ingredients salvianolic acid B (Sal B), tanshinone IIA (Tansh) and protocatechuic acid (Protoc) under tumor necrosis factor (TNF)-α or ADP stimulation. Expression of CD40 and cellular adhesion molecules (VCAM-1/ICAM-1) were assessed via flow cytometry. Levels of interleukin (IL)-6, IL-8, monocyte-chemoattractant-protein (MCP)-1 as well as soluble VCAM1 and ICAM-1 in the supernatants were examined via luminex based analysis. Treatment with DS attenuated TNF-α induced expression of CD40. Furthermore, the expression of VCAM-1 and ICAM-1 as well as the release of soluble VCAM-1 and ICAM-1 were downregulated. In the cell supernatants we also observed a significant reduction of IL-6, IL8 and MCP-1. DS and its major ingredients, Sal B and Protoc, significantly inhibited TNF-induced expression and release of adhesion molecules, cytokines and chemokines as well as ADP-induced expression of platelet P-selectin. Because of the key roles of inflammatory mediators in the etiology of atherosclerosis, this work provides useful insight in understanding the pharmacological efficacy of Chinese herbal medicine.

Low-dose dual-source CT angiography with iterative reconstruction for coronary artery stent evaluation.

OBJECTIVES: The purpose of this study was to evaluate the image quality and diagnostic accuracy of very low-dose, dual-source computed tomography (DSCT) angiography for the evaluation of coronary stents. BACKGROUND: Iterative reconstruction (IR) leads to substantial reduction of image noise and hence permits the use of very low-dose data acquisition protocols in coronary computed tomography angiography. METHODS: Fifty symptomatic patients with 87 coronary stents (diameter 3.0 ± 0.4 mm) underwent coronary DSCT angiography (heart rate, 60 ± 6 beats/min; prospectively electrocardiography-triggered axial acquisition; 80 kV, 165 mA, 2 × 128 × 0.6-mm collimation; 60 ml of contrast at 6 ml/s) before invasive coronary angiography. DSCT images were reconstructed using both standard filtered back projection and a raw data-based IR algorithm (SAFIRE, Siemens Healthcare, Forchheim, Germany). Subjective image quality (4-point scale from 0 [nondiagnostic] to 3 [excellent image quality]), image noise, contrast-to-noise ratio as well as the presence of in-stent stenosis >50% were independently determined by 2 observers. RESULTS: The median dose-length product was 23.0 (22.0; 23.0) mGy · cm (median estimated effective dose of 0.32 [0.31; 0.32] mSv). IR led to significantly improved image quality compared with filtered back projection (image quality score, 1.8 ± 0.6 vs. 1.5 ± 0.5, p < 0.05; image noise, 70 Hounsfield units [62; 80 Hounsfield units] vs. 96 Hounsfield units [82; 113 Hounsfield units], p < 0.001; contrast-to-noise ratio, 11.0 [9.6; 12.4] vs. 8.0 [6.2; 9.3], p < 0.001). To detect significant coronary stenosis in filtered back projection reconstructions, the sensitivity, specificity, positive predictive value, and negative predictive value were 97% (32 of 33), 53% (9 of 17), 80% (32 of 40), and 90% (9 of 10) per patient, respectively; 89% (43 of 48), 79% (120 of 152), 57% (42 of 74), and 96% (121 of 126) per vessel, respectively; and 85% (12 of 14), 69% (51 of 73), 32% (11 of 34), and 96% (51 of 53) per stent, respectively. In reconstructions obtained by IR, the corresponding values were 100% (33 of 33), 65% (11 of 17), 85% (33 of 39), and 100% (11 of 11) per patient, respectively; 96% (46 of 48), 84% (129 of 152), 66% (47 of 71), and 98% (127 of 129) per vessel, respectively; and 100% (14 of 14), 75% (55 of 73), 44% (14 of 32), and 100% (55 of 55) per stent, respectively. These differences were not significant. CONCLUSIONS: In selected patients, prospectively electrocardiography-triggered image acquisition with 80-kV tube voltage and low current in combination with IR permits the evaluation of patients with implanted coronary artery stents with reasonable diagnostic accuracy at very low radiation exposure.

Invasive hemodynamic characteristics of low gradient severe aortic stenosis despite preserved ejection fraction.

OBJECTIVES: The study sought to compare echocardiographic with invasive hemodynamic data in patients with "paradoxic" aortic stenosis and in patients with conventionally defined severe aortic stenosis. BACKGROUND: Controversy exists whether low gradient severe aortic stenosis despite preserved ejection fraction ("paradoxic" aortic stenosis; aortic valve area <1 cm(2), mean gradient <40 mm Hg, ejection fraction >50%), which has been mainly diagnosed by echocardiography (echo), may be largely due to mistakes in echocardiographic measurements. METHODS: We compared echocardiographic and invasive hemodynamic data from 58 patients (43% male, mean age 77 ± 5 years) with "paradoxic" aortic stenosis. Data of 22 patients (45% male, mean age 73 ± 7 years) with conventionally defined severe aortic stenosis area (aortic valve area ≤1 cm(2), mean gradient >40 mm Hg, ejection fraction ≥50%) were also analyzed. RESULTS: In patients with "paradoxic" aortic stenosis, orifice area by echo (0.80 ± 0.15 cm(2)) and catheterization showed modest agreement, whether stroke volume was measured by oxymetry (0.69 ± 0.16 cm(2), bias 0.14 ± 0.17 cm(2)), or by thermodilution (0.85 ± 0.19 cm(2), bias -0.03 ± 0.19 cm(2)). Mean systolic gradients were very similar (32 ± 7 mm Hg vs. 31 ± 6 mm Hg; bias -0.08 ± 7.8 mm Hg). In comparison, in patients with conventionally defined severe aortic stenosis, orifice area by echo was 0.72 ± 0.17 cm(2) and by catheterization 0.51 ± 0.15 cm(2) (oxymetry) and 0.68 ± 0.21 cm(2) (thermodilution), respectively, and mean systolic gradient 51 ± 10 mm Hg and 55 ± 8 mm Hg, respectively. Ejection fractions did not differ significantly in both groups. Ascending aortic diameter was significantly smaller in the "paradoxic" aortic stenosis group than in patients with conventionally defined severe aortic stenosis (28 ± 5 mm vs. 31 ± 5 mm), and energy loss index was significantly larger (0.51 ± 0.12 cm(2)/m(2) vs. 0.42 ± 0.09 cm(2)/m(2), respectively). Heart rate and mean blood pressure during echo and catheterization were not significantly different. CONCLUSIONS: Occurrence of low gradient severe aortic stenosis despite preserved ejection fraction was confirmed by invasive hemodynamics and was not the result of a systematic bias in the echo calculation of aortic orifice area.

CT predictors of post-procedural aortic regurgitation in patients referred for transcatheter aortic valve implantation: an analysis of 105 patients.

Cardiac computed tomography (CT) allows accurate and detailed analysis of the anatomy of the aortic root and valve, including quantification of calcium. We evaluated the correlation between different CT parameters and the degree of post-procedural aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) using the balloon-expandable Edwards Sapien prosthesis. Pre-intervention contrast-enhanced dual source CT data sets of 105 consecutive patients (48 males, mean age 81 ± 6 years, mean logEuroSCORE 34 ± 13%) with symptomatic severe aortic valve stenosis referred for TAVI using the Edwards Sapien prosthesis (Edwards lifesciences, Inc., CA, USA) were analysed. The degrees of aortic valve commissural calcification and annular calcification were visually assessed on a scale from 0 to 3. Furthermore, the degree of aortic valve calcification as quantified by the Agatston score, aortic annulus eccentricity, aortic diameter at the level of the sinus of valsalva and at the sinotubular junction were assessed. Early post-procedural AR was assessed using aortography. Significant AR was defined as angiographic AR of at least moderate degree (AR ≥ 2). Visual assessment of the degree of aortic annular calcification as well as the Agatston score of aortic valve calcium correlated weakly, yet significantly with the degree of post-procedural AR (r = 0.31 and 0.24, p = 0.001 and 0.013, respectively). Compared to patients with AR < 2, patients with AR ≥ 2 showed more severe calcification of the aortic annulus (mean visual scores 1.9 ± 0.6 vs. 1.5 ± 0.6, p = 0.003) as well as higher aortic valve Agatston scores (1,517 ± 861 vs. 1,062 ± 688, p = 0.005). Visual score for commissural calcification did not differ significantly between both groups (mean scores 2.4 ± 0.5 vs. 2.5 ± 0.5, respectively, p = 0.117). No significant correlation was observed between the degree of AR and commissural calcification, aortic annulus eccentricity index or aortic diameters. The extent of aortic valve annular calcification, but not of commissural calcification, predicts significant post-procedural AR in patients referred for TAVI using the balloon-expandable Edwards Sapiens prosthesis.

Additional diagnostic and prognostic value of copeptin ultra-sensitive for diagnosis of non-ST-elevation myocardial infarction in older patients presenting to the emergency department.

BACKGROUND: Identifying older patients with non-ST- elevation myocardial infarction (NSTEMI) within the very large proportion with elevated high-sensitive cardiac troponin T (hs-cTnT) is a diagnostic challenge because they often present without clear symptoms or electrocardiographic features of acute coronary syndrome to the emergency department (ED). We prospectively investigated the diagnostic and prognostic performance of copeptin ultra-sensitive (copeptin-us) and hs-cTnT compared to hs-cTnT alone for NSTEMI at prespecified cut-offs in unselected older patients. METHODS: We consecutively enrolled 306 non-surgical patients ≥70 years presenting to the ED. In addition to clinical examination, copeptin-us and hs-cTnT were measured at admission. Two cardiologists independently adjudicated the final diagnosis of NSTEMI after reviewing all available data. All patients were followed up for cardiovascular-related death within the following 12 months. RESULTS: NSTEMI was diagnosed in 38 (12%) patients (age 81±6 years). The combination of copeptin-us ≥14 pmol/L and hs-cTnT ≥0.014 µg/L compared to hs-cTnT ≥0.014 µg/L alone had a positive predictive value of 21% vs. 19% to rule in NSTEMI. The combination of copeptin-us <14 pmol/L and hs-cTnT <0.014 µg/L compared to hs-cTnT <0.014 µg/L alone had a negative predictive value of 100% vs. 99% to rule out NSTEMI. Hs-cTnT ≥0.014 µg/L alone was significantly associated with outcome. When copeptin-us ≥14 pmol/L was added, the net reclassification improvement for outcome was not significant (p=0.809). CONCLUSIONS: In unselected older patients presenting to the ED, the additional use of copeptin-us at predefined cut-offs may help to reliably rule out NSTEMI but may not help to increase predicted risk for outcome compared to hs-cTnT alone.

Very low-dose coronary artery calcium scanning with high-pitch spiral acquisition mode: comparison between 120-kV and 100-kV tube voltage protocols.

BACKGROUND: Effective radiation dose from a single coronary artery calcification CT scan can range from 0.8 to 10.5 mSv, depending on the protocol. Reducing the effective radiation dose to reasonable levels without affecting diagnostic image quality can result in substantial dose reduction in CT. OBJECTIVES: We prospectively compared tube voltages of 120 and 100 kV in a low-dose CT acquisition protocol for measuring coronary artery calcified plaque with prospectively electrocardiogram (ECG)-triggered high-pitch spiral acquisition. METHODS: In 150 consecutive patients, measurement of coronary artery calcified plaque was performed with prospectively ECG-triggered high-pitch spiral acquisition. Imaging was first done with tube voltage of 120 kV voltage and subsequently repeated with 100 kV and otherwise unchanged parameters. CT was performed with a dual-source CT system with 280 milliseconds of rotation time, 2 × 128 slices, pitch of 3.4, triggered at 60% of the R-R interval. Tube current for both protocols was set at 80 mAs. With the use of a medium sharp reconstruction kernel (Siemens B35f), cross-sectional images were reconstructed with 3.0-mm slice thickness and 1.5-mm increment. Agatston scores were determined per patient for both scan settings by 2 independent readers with the use of a standard threshold of 130 HU for calcium detection. In addition, the Agatston score was calculated with a previously proposed threshold of 147 HU for 100-kV acquisitions. RESULTS: Mean image noise was 20 ± 5 and 27 ± 7 for 120 and 100 kV, respectively (P < 0.0001). Mean dose length product was 24 ± 6 cm · cGy for the 120-kV protocol and 14 ± 4 cm · cGy for the 100-kV protocol, corresponding to average estimated effective doses of 0.3 and 0.2 mSv (P < 0.0001). Five patients were excluded from the analysis. In the remaining 145 patients, using the standard tube voltage of 120 kV, any coronary calcium was detected in 76 identical patients by both observers. In 75 of these patients, calcium was also identified by both observers in 100-kV data sets, whereas 1 patient was scored negative by 1 reader and was assigned an Agatston score of 0.7 (threshold, 130 HU) and 0.2 (threshold, 147 HU) by the other. Interobserver disagreement for assigning a patient a zero Agatston score was the same for both scan settings (each 4 patients). The mean Agatston scores for 120-kV and 100-kV (threshold, 147 HU) scans were 105 ± 245 (range, 0-1865) and 116 ± 261 (range, 0-1917), respectively (P < 0.0001). Bland-Altman analysis indicated a systematic overestimation of the Agatston score with tube voltage of 100 kV and threshold of 147 HU (mean difference, 11; 95% limits of agreement, 62 to -40). Similar results were observed for coronary calcium volume scores. CONCLUSION: High-pitch spiral acquisition allows coronary calcium scoring with effective doses below 0.5 mSv. The use of 100-kV tube voltage further reduces effective radiation dose compared with the standard of 120 kV; however, it leads to significant overestimation of the Agatston score when the standard threshold of 130 HU is used. Adjusting the threshold to 147 HU leads to a better agreement compared with standard 120 kV protocols yet with a remaining systematic bias toward overestimation of the Agatston score. For high-pitch spiral acquisition mode, effective radiation dose reduction when using a 100-kV setting is minimal compared with the standard 120-kV setting and may be considered nonsignificant in a clinical setting.

Patient-specific predictors of image noise in coronary CT angiography.

BACKGROUND: Coronary computed tomography (CT) angiography can be associated with high radiation exposure. Reduction of tube voltage from 120 kV to 100 kV can reduce the dose by up to 40%, but it also increases image noise. OBJECTIVE: We aimed to find a patient-specific predictor of image noise to determine the use of reduced tube voltage. METHODS: Contrast-enhanced coronary dual-source CT angiography data sets [prospectively electrocardiogram (ECG)-triggered axial and retrospectively ECG-gated spiral acquisition, rotation of 280 milliseconds, 2 × 128 × 0.6 mm collimation, 100 kV, 320 mAs] of 165 patients (age, 54 ± 13 years) for the detection of coronary artery stenoses were analyzed. Image noise was measured in the aortic root. Influence of body weight, height, body mass index, thoracic cross sectional area, as well as the area of the thoracic solid tissue were analyzed. RESULTS: Mean image noise in the aorta was 35.1 ± 8.9 HU. Mean dose length product was 207 ± 184 cm · cGy with an average effective dose of 2.9 ± 2.6 mSv. The patient cohort was divided into tertiles according to image noise. Numerous parameters, including BMI and body weight, were significantly different between the highest and lowest tertiles. In multivariable regression analysis, the area of the thoracic solid tissue was the only independent predictor of image noise (P < 0.0001). CONCLUSIONS: The area of the thoracic solid tissue at the level of the aortic root predicts image noise and may hence be used for the decision to reduce tube voltage from 120 kV to 100 kV.

Image quality of ultra-low radiation exposure coronary CT angiography with an effective dose <0.1 mSv using high-pitch spiral acquisition and raw data-based iterative reconstruction.

OBJECTIVES: We evaluated the potential of prospectively ECG-triggered high-pitch spiral acquisition with low tube voltage and current in combination with iterative reconstruction to achieve coronary CT angiography with sufficient image quality at an effective dose below 0.1 mSv. METHODS: Contrast-enhanced coronary dual source CT angiography (2 × 128 × 0.6 mm, 80 kV, 50 mAs) in prospectively ECG-triggered high-pitch spiral acquisition mode was performed in 21 consecutive individuals (body weight <100 kg, heart rate ≤60/min). Images were reconstructed with raw data-based filtered back projection (FBP) and iterative reconstruction (IR). Image quality was assessed on a 4-point scale (1 = no artefacts, 4 = unevaluable). RESULTS: Mean effective dose was 0.06 ± 0.01 mSv. Image noise was significantly reduced in IR (128.9 ± 46.6 vs. 158.2 ± 44.7 HU). The mean image quality score was lower for IR (1.9 ± 1.1 vs. 2.2 ± 1.0, P < 0.0001). Of 292 coronary segments, 55 in FBP and 40 in IR (P = 0.12) were graded "unevaluable". In patients with a body weight ≤75 kg, both in FBP and in IR, the rates of fully evaluable segments were significantly higher in comparison to patients >75 kg. CONCLUSIONS: Coronary CT angiography with an estimated effective dose <0.1 mSv may provide sufficient image quality in selected patients through the combination of high-pitch spiral acquisition and raw data-based iterative reconstruction.

Accuracy of automated software-guided detection of significant coronary artery stenosis by CT angiography: comparison with invasive catheterisation.

PURPOSE: True automated detection of coronary artery stenoses might be useful whenever expert evaluation is not available, or as a "second reader" to enhance diagnostic confidence. We evaluated the accuracy of a PC-based stenosis detection tool alone and combined with expert interpretation. METHODS: One hundred coronary CT angiography datasets were evaluated with the automated software alone, by manual interpretation (axial images, multiplanar reformations and maximum intensity projections in free double-oblique planes), and by expert interpretation aware of the automated findings. Stenoses ≥ 50 % were noted per-vessel and per-patient, and compared with invasive angiography. RESULTS: Automated post-processing was successful in 90 % of patients (88 % of vessels). When excluding uninterpretable datasets, per-patient sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 89 %, 79 %, 74 % and 92 % (per-vessel: 82 %, 85 %, 48 % and 96 %). All 100 datasets were evaluable by expert interpretation. Per-patient sensitivity, specificity, PPV and NPV were 95 %, 95 %, 93 % and 97 % (per-vessel: 89 %,98 %, 88 % and 98 %). Knowing the results of automated interpretation did not improve the performance of expert readers. CONCLUSION: Automated off-line post-processing of coronary CT angiography shows adequate sensitivity, but relatively low specificity in coronary stenosis detection. It does not increase accuracy of expert interpretation. Failure of post-processing in 10 % of all patients necessitates additional manual image work-up. KEY POINTS: • Coronary CT angiography is increasingly used for detection of coronary artery stenosis • Computer assisted diagnosis might facilitate and speed up interpretation • Performance in properly segmented cases compared favourably with manual image interpretation • However, automated segmentation failed in about 10 % of cases • Manual reading is still mandatory; computer assisted diagnosis can provide a useful second read.

A myocardial ischemia- and reperfusion-induced injury is mediated by reactive oxygen species released from blood platelets.

In recent experimental studies, blood platelets have been found to exhibit some cardiodepressive effects in ischemic and reperfused guinea pig hearts independent of thrombus formation. These effects seemed to be mediated by reactive oxygen species (ROS). However, the source of these ROS - platelets or heart - remained still unknown. Isolated, buffer-perfused and pressure-volume work performing guinea pig hearts were exposed to a low-flow ischemia (1 ml/min) of 30 min duration and reperfused at a constant flow of 5 ml/min. Human thrombocytes were administered as 1 min bolus (20 000 thrombocytes/µl perfusion buffer) in the 15th min of ischemia or in the 1st or 5th min of reperfusion in the presence of thrombin (0.3 U/ml perfusion buffer). Recovery of external heart work (REHW) was expressed as ratio between postischemic and preischemic EHW in percent. Intracoronary platelet retention (RET) was quantified as percent of platelets applied. In a second set of experiments, thrombocytes were incubated with 10 µM of the irreversible NADPH oxidase blocker diphenyliodonium chloride and washed twice, thereafter, and administered according to the same protocol as described above. Hearts exposed to ischemia and reperfusion in the presence of thrombin but without application of platelets served as controls. Controls without application of platelets did not reveal a severe compromisation of myocardial function (REHW 85.5 ± 1%). However, addition of platelets during ischemia or in the 1st or 5th min of reperfusion led to a significant reduction of REHW as compared with controls (REHW 62.4 ± 6, 53.9 ± 3, 40.5 ± 3, respectively). Application of platelets pretreated with diphenyliodonium chloride did not reveal any cardiodepressive effects being significantly different from controls without platelet application. Moreover, treatment of platelets with diphenyliodonium chloride did not significantly decrease intracoronary platelet retention. In conclusion, these results demonstrate that cardiodepressive effects of human thrombocytes in ischemic and reperfused guinea pig hearts are mediated by ROS released from thrombocytes and not the heart.

Out-of-hospital cardiac arrest and percutaneous coronary intervention for ST-elevation myocardial infarction: long-term survival and neurological outcome.

BACKGROUND: Predictors of long-term outcome after ST-elevation myocardial infarction (STEMI) complicated by out-of-hospital cardiac arrest (OHCA) are incompletely understood, including the influence of successful coronary reperfusion. METHODS: We analysed clinical and procedural data as well as 1-year outcome of 72 consecutive patients who underwent primary coronary intervention (PCI) after witnessed OHCA and STEMI and compared the results with 695 patients with STEMI and PCI, but without OHCA. Neurological recovery after OHCA was assessed using the Cerebral Performance Category (CPC) scale. RESULTS: PCI was successful in 83.3% after OHCA vs. 84.3% in the non-OHCA group (p=0.87). One-year mortality was 34.7% vs. 9.5% (p<0.001). 58.3% of the OHCA-patients showed complete neurological recovery (CPC 1) or moderate neurological disability (CPC 2). Another 6.9% showed severe cerebral disability (CPC 3) or permanent vegetative status (CPC 4). Delay from collapse until start of Advanced Cardiopulmonary Life Support (ACLS) was shorter for survivors with CPC status ≤2 (median 1 min, range 0-11 min) compared to non-survivors or survivors with CPC status >2 (median 8 min, range 0-13 min), p<0.0001. Age-adjusted multivariate analysis identified 'unsuccessful PCI', 'vasopressors on admission' and 'start of ACLS after >6 min' as independent predictors of negative long-term outcome (death or CPC >2). CONCLUSIONS: Mortality is high in patients with STEMI complicated by OHCA - even though PCI was performed with the same success rate as in patients without OHCA. The majority of survivors had favourable neurological outcomes at 1 year, especially if advanced life support had been started within ≤6 min and PCI was successful.

A method to determine suitable fluoroscopic projections for transcatheter aortic valve implantation by computed tomography.

BACKGROUND: In transcatheter aortic valve implantation (TAVI), optimal selection of fluoroscopic projections that permit orthogonal visualization of the aortic valve plane is important but may be difficult to achieve. OBJECTIVE: We developed and validated a simple method to predict suitable fluoroscopic projections on the basis of cardiac CT datasets. METHODS: In 75 consecutive patients that underwent TAVI, angulations in which a 35-mm thick maximum intensity projection would render all aortic valve calcium into 1 plane were determined by manual interaction with contrast-enhanced dual-source CT datasets. TAVI operators used the predicted angulation for the first aortic angiogram and performed additional aortic angiograms if no satisfactory view of the aortic valve plane was obtained. Predicted angulations were compared with the angulation used for valve implantation. Radiation exposure and contrast use was compared between patients with accurate prediction of fluoroscopic angulations by CT and patients in whom CT failed to predict a suitable view. RESULTS: The mean difference between the predicted angulation according to CT and the angulation used for implantation was 3 ± 6 degrees. CT predicted a suitable angulation (<5-degree deviation) in 63 of 75 cases (84%). The mean number of aortic angiograms acquired in patients with correct prediction (1.02 ± 0.1) was significantly lower than in patients with incorrect prediction of the implantation angle by CT (3.0 ± 1.7; P < 0.001). Contrast agent required for the entire TAVI procedure was lower in patients with correct prediction (72 ± 36 mL vs 106 ± 39 mL; P = 0.001). CONCLUSION: CT permits prediction of suitable angulations for TAVI in most cases.

Suppression of dendritic cell functions contributes to the anti-inflammatory action of granulocyte-colony stimulating factor in experimental stroke.

Cerebral ischemia provokes an inflammatory cascade, which is assumed to secondarily worsen ischemic tissue damage. Linking adaptive and innate immunity dendritic cells (DCs) are key regulators of the immune system. The hematopoietic factor G-CSF is able to modulate DC-mediated immune processes. Although G-CSF is under investigation for the treatment of stroke, only limited information exists about its effects on stroke-induced inflammation. Therefore, we investigated the impact of G-CSF on cerebral DC migration and maturation as well as on the mediated immune response in an experimental stroke model in rats by means of transient middle cerebral artery occlusion (tMCAO). Immunohistochemistry and quantitative PCR were performed of the ischemic brain and flow cytometrical analysis of peripheral blood. G-CSF led to a reduction of the infarct size and an improved neurological outcome. Immunohistochemistry confirmed a reduced migration of DCs and mature antigen-presenting cells after G-CSF treatment. Compared to the untreated tMCAO group, G-CSF led to an inhibited DC activation and maturation. This was shown by a significantly decreased cerebral transcription of TLR2 and the DC maturation markers, CD83 and CD86, as well as by an inhibition of stroke-induced increase in immunocompetent DCs (OX62⁺OX6⁺) in peripheral blood. Cerebral expression of the proinflammatory cytokine TNF-α was reduced, indicating an attenuation of cerebral inflammation. Our data suggest an induction of DC migration and maturation under ischemic conditions and identify DCs as a potential target to modulate postischemic cerebral inflammation. Suppression of both enhanced DC migration and maturation might contribute to the neuroprotective action of G-CSF in experimental stroke.

Interobserver agreement for the detection of atherosclerotic plaque in coronary CT angiography: comparison of two low-dose image acquisition protocols with standard retrospectively ECG-gated reconstruction.

BACKGROUND: We compared the interobserver variability concerning the detection of calcified and non-calcified plaque in two different low-dose and standard retrospectively gated protocols for coronary CTA. METHODS: 150 patients with low heart rates and less than 100 kg body weight were randomised and examined by contrast-enhanced dual-source CT coronary angiography (100 kV, 320 mAs). 50 patients were examined with prospectively ECG-triggered axial acquisition, 50 patients with prospectively ECG-triggered high pitch spiral acquisition, and 50 patients using spiral acquisition with retrospective ECG gating. Two investigators independently analysed the datasets concerning the presence of calcified and non-calcified plaque on a per-segment level. RESULTS: Mean effective dose was 1.4 ± 0.2 mSv for axial, 0.8 ± 0.07 mSv for high-pitch spiral, and 5.3 ± 2.6 mSV for standard spiral acquisition (P < 0.0001). In axial acquisition, interobserver agreement concerning the presence of atherosclerotic plaque was achieved in 650/749 coronary segments (86.8%). In high-pitch spiral acquisition, agreement was achieved in 664/748 segments (88.8%, n.s.). In standard spiral acquisition, agreement was achieved in 672/738 segments (91.0%, P < 0.0001). Interobserver agreement was significantly higher for calcified than for non-calcified plaque in all data acquisition modes. CONCLUSION: Low-dose coronary CT angiography permits the detection of coronary atherosclerotic plaque with good interobserver agreement. KEY POINTS: • Low-dose CT protocols permit coronary plaque detection with good interobserver agreement. • Image noise is a major predictor of interobserver variability. • Interobserver agreement is significantly higher for calcified than for non-calcified plaque.

Shear stress patterns affect the secreted chemokine profile in endothelial cells.

BACKGROUND: Atherosclerotic plaques are initiated by pro-inflammatory endothelial activation at arterial regions subjected to non-uniform shear stress. We applied the in vitro flow-through cell culture slides to investigate whether different patterns of shear stress affect the secreted cytokine and chemokine profile in endothelial cells. METHODS: Human umbilical vein endothelial cells (ECs) were exposed to 24 h of flow in straight or bifurcating flow-through slides, in some experiments followed by 6 h stimulation with 2.5 ng/mL TNF-α. IL-1ß, IL-6, IL-8, IL-12p70, MIP-1α, MCP-1 and sICAM-1 were measured in conditioned medium samples by flow cytometry using antibodies conjugated with fluorescent beads. RESULTS: The release of IL-1ß, IL-12p70 and MIP-1α from endothelial cells exposed to shear stress was below detectable levels. Strongly increased level of sICAM and significantly increased IL-8 concentration were detected in conditioned medium from endothelial cells exposed to flow in bifurcating slides as compared with cells grown under laminar flow in straight channels. The release of IL-6 and MCP-1 was not significantly induced in bifurcating slides. Treatment with TNF-α for 6 h induced 2-3 fold increase in secreted chemokines and cytokines. In particular, significantly increased MCP-1 and increased IL-8 levels were released from endothelial cells grown in bifurcating slides. This release was partly prevented in cells grown in straight channels, i.e. under exposure to laminar flow only. CONCLUSIONS: Although the endothelial monolayer areas exposed to non-uniform shear stress are relatively small, the activation of cells in these regions is strong enough to produce a detectable change in cytokine and chemokine profile, which represents the earliest step in atherogenic endothelial dysfunction.

Influence of heart rate and phase of the cardiac cycle on the occurrence of motion artifact in dual-source CT angiography of the coronary arteries.

BACKGROUND: Coronary CT angiography allows visualization of the coronary arteries. However, motion artifact can impair delineation of the coronary artery lumen and detection of coronary artery stenoses. OBJECTIVE: We investigated the influence of heart rate and the segment of the cardiac cycle during which images are reconstructed on the occurrence of motion artifacts. METHODS: We evaluated coronary CT angiography datasets obtained by 64-slice dual-source CT in 100 consecutive patients. Data were reconstructed at 13 time instants during the cardiac cycle and evaluated for the presence of motion artifact. RESULTS: Mean heart rate was 66±14 beats/min. Overall, 98 of 100 patients had evaluable datasets. For heart rates ≤60 beats/min, optimal image quality was uniformly found during late diastole (100% of cases with evaluable image quality during a time window between 65% and 75% of the cardiac cycle). With increasing heart rates, images reconstructed during late systole more frequently provided best image quality. However, image reconstruction could not be restricted to a systolic time period. To achieve evaluable image quality in 95% of cases, data acquired between 25% and 75% of the cardiac cycle had to be available for patients with heart rates >60 beats/min. CONCLUSION: Dual-source CT provides high image quality across a wide range of heart rates. Although data acquisition may be limited to diastole for patients with heart rates ≤60 beats/min, the availability of data acquired both during systole and diastole is necessary for patients with higher heart rates.