Long-term clinical outcome after intracoronary application of bone marrow-derived mononuclear cells for acute myocardial infarction: migratory capacity of administered cells determines event-free survival.

BACKGROUND: In the REPAIR-AMI trial, intracoronary infusion of bone marrow-derived cells (BMCs) was associated with a significantly greater recovery of contractile function in patients with acute myocardial infarction (AMI) at 4-month follow-up than placebo infusion. The current analysis investigates clinical outcome and predictors of event-free survival at 5 years. METHODS AND RESULTS: In the multicentre, placebo-controlled, double-blind REPAIR-AMI trial, 204 patients received intracoronary infusion of BMCs (n = 101) or placebo (n = 103) into the infarct vessel 3-7 days following successful percutaneous coronary intervention. Fifteen patients died in the placebo group compared with seven patients in the BMC group (P = 0.08). Nine placebo-treated patients and five BMC-treated patients required rehospitalization for chronic heart failure (P = 0.23). The combined endpoint cardiac/cardiovascular/unknown death or rehospitalisation for heart failure was more frequent in the placebo compared with the BMC group (18 vs. 10 events; P = 0.10). Univariate predictors of adverse outcomes were age, the CADILLAC risk score, aldosterone antagonist and diuretic treatment, changes in left ventricular ejection fraction, left ventricular end-systolic volume, and N-terminal pro-Brain Natriuretic Peptide (all P < 0.01) at 4 months in the entire cohort and in the placebo group. In contrast, in the BMC group, only the basal (P = 0.02) and the stromal cell-derived factor-1-induced (P = 0.05) migratory capacity of the administered BMC were associated with improved clinical outcome. CONCLUSION: In patients of the REPAIR-AMI trial, established clinical parameters are associated with adverse outcome at 5 years exclusively in the placebo group, whereas the migratory capacity of the administered BMC determines event-free survival in the BMC-treated patients. These data disclose a potency-effect relationship between cell therapy and long-term outcome in patients with AMI.

Quantitative analysis of coronary plaque composition by dual-source CT in patients with acute non-ST-elevation myocardial infarction compared to patients with stable coronary artery disease correlated with virtual histology intravascular ultrasound.

RATIONALE AND OBJECTIVES: To quantitatively assess coronary atherosclerotic plaque composition in patients with acute non-ST elevation myocardial infarction (NSTEMI) and patients with stable coronary artery disease (CAD) by coronary computed tomography angiography (cCTA) correlated with virtual histology intravascular ultrasound (VH-IVUS). MATERIALS AND METHODS: Sixty patients (35 with NSTEMI) were included. Corresponding plaques were assessed by dual-source cCTA and VH-IVUS regarding volumes and percentages of fatty, fibrous, and calcified component; overall plaque burden; and maximal percent area stenosis. Possible differences between patient groups were investigated. Concordance between cCTA and VH-IVUS measurements was validated by Bland-Altman analysis. RESULTS: Forty corresponding plaques (22 of patients with NSTEMI) were finally analyzed by cCTA and VH-IVUS. cCTA plaque analysis revealed no significant differences between plaques of patients with NSTEMI and stable CAD regarding absolute and relative amounts of any plaque component (fatty: 20 mm³/13% versus 17 mm³/14%; fibrous: 81 mm³/63% versus 80 mm³/53%; calcified: 16 mm³/14% versus 26 mm³/26%; all P > .05) or overall plaque burden (153 mm³ versus 165 mm³; P > .05), nor did VH-IVUS plaque analysis. VH-IVUS measured a higher area stenosis in patients with NSTEMI compared to patients with stable CAD (76% versus 68%, P = .01; in cCTA 69% versus 65%, P = .2). Volumes of fatty component were measured systematically lower in cCTA, whereas calcified and fibrous volumes were higher. No significant bias was observed comparing volumes of overall noncalcified component and overall plaque burden. CONCLUSION: Plaques of patients with acute NSTEMI and of patients with stable CAD cannot be differentiated by quantification of plaque components. cCTA and VH-IVUS differ in plaque component analysis.

Coronary computed tomography and triple rule out CT in patients with acute chest pain and an intermediate cardiac risk profile. Part 1: impact on patient management.

OBJECTIVE: To evaluate the impact of coronary CT angiography (coronary CTA) or "triple-rule-out" CT angiography (TRO-CTA) on patient management in the work-up of patients with acute chest pain and an intermediate cardiac risk profile. MATERIALS AND METHODS: 100 patients with acute chest pain and an intermediate cardiac risk for acute coronary syndrome (ACS) underwent coronary CTA or TRO-CTA for the evaluation of chest pain. Patients with a high and low cardiac risk profile were not included in this study. All patients with significant coronary stenosis >50% on coronary CTA underwent invasive coronary catheterization (ICC). Important other pathological findings were recorded. All patients had a 90-day follow-up period for major adverse cardiac events (MACE). RESULTS: Based on a negative coronary CTA 60 of 100 patients were discharged on the same day. None of the discharged patients showed MACE during the 90-day follow-up. Coronary CTA revealed a coronary stenosis >50% in 19 of 100 patients. ICC confirmed significant coronary stenosis in 17/19 patients. Among the 17 true positive patients, 9 underwent percutaneous coronary intervention with stent implantation, 7 were received intensified medical therapy, and 1 patient underwent coronary artery bypass surgery. A TRO-CTA protocol was performed in 36/100 patients due to elevated d-dimer levels. Pulmonary embolism was present in 5 patients, pleural effusion of unknown etiology in 3 patients, severe right ventricular dysfunction with pericardial effusion in 1 patient, and an incidental bronchial carcinoma was diagnosed in 1 patient. CONCLUSION: Coronary CTA and TRO-CTA allow a rapid and safe discharge in the majority of patients presenting with acute chest pain and an intermediate risk for ACS while at the same time identifies those with significant coronary artery stenosis.

Aortoiliac CT angiography for planning transcutaneous aortic valve implantation: aortic root anatomy and frequency of clinically significant incidental findings.

OBJECTIVE: The purpose of this article is to assess aortic root and iliofemoral vessel anatomy and the frequency of clinically significant incidental findings on aortoiliac CT angiography (CTA) performed for planning of transcutaneous aortic valve implantation. MATERIALS AND METHODS: Aortoiliac CTA studies of 207 patients scheduled for transcutaneous aortic valve implantation were analyzed. Anatomic dimensions relevant to the interventional procedure, including diameter of the aortic annulus and sinus of Valsalva, distance between aortic annulus and coronary ostia, coronary leaflet length, left ventricular outflow tract diameter, and vessel diameter of iliac arteries, were analyzed. Clinically significant incidental findings were recorded. RESULTS: The mean (± SD) maximum and minimum diameters of the aortic annulus were 29 ± 3.9 mm and 23.5 ± 4.1 mm, respectively. The mean distances between aortic annulus and the ostium of the left and right coronary artery were 13.5 ± 3.2 mm and 14.8 ± 3.9 mm, respectively. The mean maximum and minimum diameters of the left ventricular outflow tract were 27 ± 4 mm and 1.9 ± 4 mm, respectively. The mean diameter of the sinus of Valsalva was 33.4 ± 5.1 mm. The mean diameters of the right and left external iliac artery were 8 ± 1 and 8 ± 2 mm, respectively. Almost half the patients (101/207) had clinically significant incidental findings, including noncalcified pulmonary nodules larger than 8 mm (n = 7), pulmonary embolism (n = 3), or aortic aneurysm (n = 12). CONCLUSION: Aortoiliac CTA provides relevant information on aortic root and iliofemoral vessel anatomy for preinterventional planning. CTA reveals clinically significant incidental findings in a high number of patients considered for transcutaneous aortic valve implantation, which may have a significant impact on patient selection.

Triple-rule-out dual-source CT angiography of patients with acute chest pain: dose reduction potential of 100 kV scanning.

PURPOSE: To investigate the dose reduction potential of low kV triple-rule-out dual-source CT angiography (TRO-CTA) in non-obese (BMI ≤ 25 kg/m(2)) patients with acute chest pain. MATERIALS AND METHODS: Sixty consecutive patients were randomly assigned to two different retrospectively ECG-gated TRO-CTA protocols in this prospective trial: Thirty patients were examined with a 120-kV standard protocol (320 reference mAs with automatic tube current modulation, automatically adapted pitch and ECG-pulsing) and served as the control group (group 1), an otherwise identical 100 kV protocol was used in the other thirty patients (group 2) for a radiation dose reduction. Subjective image quality was assessed on a 5 point scale (1: excellent, 5: non-diagnostic) by two blinded observers. Quantitative image analysis assessed vascular attenuation, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in different vascular segments. The effective dose was calculated from the dose length product (DLP) using a conversion coefficient of 0.017 mSvmGy(-1)cm(-1). RESULTS: There was no significant difference of age, BMI, heart rate, pitch or scan length between both patient groups. Subjective image quality was rated similar in both groups (group 1: 1.2 ± 0.4, group 2: average score=1.3 ± 0.5). Vessel attenuation was significantly higher in group 2 than in group 1 (ascending aorta: 456 ± 83 HU vs. 370 ± 78 HU, p<0.001; pulmonary artery: 468 ± 118 HU vs. 411 ± 91 HU, p=0.03; left coronary artery: 437 ± 110 HU vs. 348 ± 89 HU, p<0.001), however, there was no significant difference in SNR (13.2 ± 7.6 vs. 14.5 ± 7.5, p=0.49) or CNR (13.8 ± 6.6 vs. 15.9 ± 7.7, p=0.25). The effective radiation dose of the 100 kV protocol was significantly lower (9.6 ± 3.2 mSv vs. 18.1 ± 9.4 mSv, p<0.0001). CONCLUSION: TRO-CTA with 100 kV is feasible in non-obese patients and results in diagnostic image quality and significantly reduced radiation dose.

Global and regional myocardial function quantification in Takotsubo cardiomyopathy in comparison to acute anterior myocardial infarction using two-dimensional (2D) strain echocardiography.

AIMS: This study sought to compare global and regional myocardial function in Takotsubo cardiomyopathy (TC) to that in acute anterior myocardial infarction (AMI) using 2D strain imaging. METHODS: Twelve consecutive patients with TC (ten women, two men) and 12 patients with AMI (four women, eight men) underwent 2D echocardiography at initial presentation. 2D strain images were analyzed to measure longitudinal and radial strain. Global strain was calculated as the average longitudinal strain of the segments of two-, three-, and four-chamber views. Biplane ejection fraction was assessed using Simpson's biplane method. RESULTS: Significant differences in radial strain (TC vs. AMI) were found in lateral (13.5 ± 10.1% vs. 25.1 ± 11.2%, P = 0.035), posterior (15.2 ± 14.5% vs. 51.4 ± 14.2%, P < 0.001), and inferior (17.9 ± 15.5% vs. 49.4 ± 16.9%, P = 0.002) segments. Longitudinal strain was significantly lower in TC in basal-inferior (-15.8 ± 9.2% vs. -22.7 ± 3.8%, P = 0.037), midinferior (-8.3 ± 9.2% vs. -16.8 ± 3.0%, P = 0.004), basal-posterior (-12.2 ± 9.4% vs. -21.6 ± 4.4%, P = 0.016), midposterior (-4.4 ± 8.0% vs. -15.4 ± 3.5%, P = 0.002), apical-posterior (2.3 ± 6.7% vs. -6.4 ± 10.1%, P = 0.023), and midlateral (-3.4 ± 6.9% vs. -9.5 ± 5.8%, P = 0.028) segments. Global strain and ejection fraction were significantly higher in patients with AMI (-3.5 ± 8.2% vs. -10.3 ± 8.4%, P < 0.001 and 37 ± 11% vs. 46 ± 11%, P = 0.045). CONCLUSION: In TC, strain was reduced around the entire mid left-ventricular circumference, whereas in AMI it was predominantly reduced in the anterior and anteroseptal wall. These observed differences confirm the notion that TC affects myocardium beyond the territory of a single coronary artery. They may allow noninvasive distinction between both entities.

Venous thromboembolism: additional diagnostic value and radiation dose of pelvic CT venography in patients with suspected pulmonary embolism.

PURPOSE: To assess the additional diagnostic value of indirect CT venography (CTV) of the pelvis and upper thighs performed after pulmonary CT angiography (CTA) for the diagnosis of venous thromboembolism (VTE). MATERIALS AND METHODS: In a retrospective analysis, the radiology information system entries between January 2003 and December 2007 were searched for patients who received pulmonary CTA and additional CTV of the pelvis and upper thighs. Of those patients, the radiology reports were reviewed for the diagnosis of pulmonary embolism (PE) and deep venous thrombosis (DVT) in the pelvic veins and veins of the upper thighs. In cases with an isolated pelvic thrombosis at CTV (i.e. which only had a thrombosis in the pelvic veins but not in the veins of the upper thigh) ultrasound reports were reviewed for the presence of DVT of the legs. The estimated radiation dose was calculated for pulmonary CTA and for CTV of the pelvis. RESULTS: In the defined period 3670 patients were referred to our institution for exclusion of PE. Of those, 642 patients (353 men, 289 women; mean age, 65±15 years, age range 18-98 years) underwent combined pulmonary CTA and CTV. Among them, PE was found in 227 patients (35.4%). In patients without PE CTV was negative in all cases. In patients with PE, CTV demonstrated pelvic thrombosis in 24 patients (3.7%) and thrombosis of the upper thighs in 43 patients (6.6%). Of those patients 14 (2.1%) had DVT in the pelvis and upper thighs. In 10 patients (1.5%) CTV showed an isolated pelvic thrombosis. Of those patients ultrasound reports were available in 7 patients, which revealed DVT of the leg veins in 5 cases (1%). Thus, the estimated prevalence of isolated pelvic thrombosis detected only by pelvic CTV ranges between 1-5/642 patients (0.1-0.7%). Radiation dose ranges between 4.8 and 9.7 mSv for additional CTV of the pelvis. CONCLUSION: CTV of the pelvis performed after pulmonary CTA is of neglectable additional diagnostic value for the detection of VTE, because the additional radiation dose is high and isolated pelvic DVT is very rare. Venous imaging of the legs (preferably by radiation-free ultrasound) is sufficient for the diagnosis of underlying DVT in patients with suspected PE.

Attenuation-based characterization of coronary atherosclerotic plaque: comparison of dual source and dual energy CT with single-source CT and histopathology.

OBJECTIVE: To compare different CT acquisition techniques regarding for attenuation-based characterization of coronary atherosclerotic plaques using histopathology as the standard of reference. MATERIALS AND METHODS: In a post mortem study 17 human hearts were studied with dual-source CT (DSCT) and dual energy CT (DECT) mode on a DSCT as well as with 16-slice single-source CT (SSCT). At autopsy, atherosclerotic lesions were cut at 5 µm sections. Histopathologic classification of the plaques according to the American Heart Association (AHA) criteria was performed by two pathologists. Attenuation values of all plaques were measured in DSCT, DECT and SSCT studies, respectively and classified based on attenuation according to modified AHA criteria. RESULTS: 58 coronary plaques were identified at autopsy. Regardless of the CT technique only 52/58 plaques were found at CT (sensitivity=89.6%). There was no significant difference between the mean attenuation values of different plaque types between DSCT, DECT, and SSCT: type IV: 11HU/8HU/19HU; type Va: 44HU/45HU/52HU; type Vb: 1088HU/966HU/1079HU). The sensitivity for correct classification varied depending on the plaque type (type II=0%, type III=0%, type IV=43%, type Va=58%, Vb=97%). CONCLUSION: Independent of the used acquisition technique, SSCT, DSCT and DECT show similar results for attenuation-based characterization of atherosclerotic coronary plaques.

Dual energy computed tomography angiography of a pulmonary embolized port catheter fragment.

We present the case of a 64-year-old woman with a history of breast cancer who underwent explantation of a dysfunctional intravenous port system. At surgery a broken port catheter was found. A port catheter fragment embolized into the segmental artery of the posterobasal segment of the right inferior lobe, causing a wedge-shaped segmental perfusion defect in the corresponding segment. The catheter was removed by catheter intervention with a goose-neck snare.

Extent of late gadolinium enhancement detected by cardiovascular magnetic resonance correlates with the inducibility of ventricular tachyarrhythmia in hypertrophic cardiomyopathy.

BACKGROUND: Myocardial fibrosis is frequently identified in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to investigate the role of myocardial fibrosis detected by late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) as a potential arrhythmogenic substrate in HCM. We hypothesized that the extent of LGE might be associated with the inducibility of ventricular tachyarrhythmias (VT) during programmed ventricular stimulation (PVS). METHODS: We evaluated retrospectively LGE CMR of 76 consecutive HCM patients, of which 43 presented with one or more risk factors for sudden cardiac death (SCD) and were therefore clinically classified as high-risk patients. Of these 43 patients, 38 additionally underwent an electrophysiological testing (EP). CMR indices and the extent of LGE, given as the % of LV mass with LGE were correlated with the presence of risk factors for SCD and the results of EP. RESULTS: High-risk patients had a significant higher prevalence of LGE than low-risk patients (29/43 [67%] versus 14/33 [47%]; p = 0.03). Also the % of LV mass with LGE was significantly higher in high-risk patients than in low-risk patients (14% versus 3%, p = 0.001, respectively). Of the 38 high- risk patients, 12 had inducible VT during EP. LV function, volumes and mass were comparable in patients with and without inducible VT. However, the % of LV mass with LGE was significantly higher in patients with inducible VT compared to those without (22% versus 10%, p = 0.03). The prevalence of LGE was, however, comparable between HCM patients with and those without inducible VT (10/12 [83%] versus 15/26 [58%]; p = 0.12). In the univariate analysis the % of LV mass with LGE and the septal wall thickness were significantly associated with the high-risk group (p = 0.001 and 0.004, respectively). Multivariate analysis demonstrated that the extent of LGE was the only independent predictor of the risk group (p = 0.03). CONCLUSIONS: The extent of LGE in HCM patients correlated with risk factors of SCD and the likelihood of inducible VT. Furthermore, LGE extent was the only independent predictor of the risk group. This supports the hypothesis that the extent of fibrosis may serve as potential arrhythmogenic substrate for the occurrence of VT, especially in patients with clinical risk factors for SCD.

Volumetric analysis of pulmonary CTA for the assessment of right ventricular dysfunction in patients with acute pulmonary embolism.

RATIONALE AND OBJECTIVES: To retrospectively determine the value of a volumetric ventricle analysis for the assessment of right ventricular dysfunction in patients with suspected pulmonary embolism (PE) by using image data from non-electrocardiographically (ECG)-gated multidetector computed tomography angiography (CTA). MATERIALS AND METHODS: Hypothesizing that the presence of PE and the embolus location correlated with right ventricular dysfunction, we retrospectively analyzed 100 non-ECG-gated pulmonary CTA datasets of patients with central, peripheral, and without PE. Right ventricle/left ventricle (RV/LV) diameter ratio measured in transverse sections (RV/LV(trans)), four-chamber view (RV/LV(4ch)), and RV/LV volume ratio (RV/LV(vol)) were assessed on CT images. The results were correlated with the embolus location, the 30-day mortality rate, and the necessity of intensive care treatment. RESULTS: All CT parameters showed statistically significant differences between all patients groups depended on embolus location. The receiver operating characteristic analysis RV/LV(vol) showed the strongest discriminatory power to differ between patients with central and without PE and between patients with central and peripheral PE (central PE vs. no PE: RV/LV(vol) = 0.932, RV/LV(trans) = 0.880, and RV/LV(4ch) = 0.811, central PE vs. peripheral PE: RV/LV(vol) = 0.950, RV/LV(trans) = 0.849, and RV/LV(4ch) = 0.881), indicating a correlation with embolus location predisposing for RVD. For the identification of high-risk patients with PE all three CT parameters showed statistically significant values (P < .0001), whereas in the receiver operating characteristic analysis, RV/LV(vol) had the strongest discriminatory power (RV/LV(vol) = 0.819, RV/LV(trans) = 0.799, and RV/LV(4ch) = 0.758). CONCLUSION: Ventricle volumetry of non-ECG-gated CTA allows the assessment of right ventricular dysfunction in patients with acute PE. Compared to unidimensional measurements, a volumetric analysis seems to be slightly superior to identify high-risk patients with adverse clinical outcome. However, the method is more time consuming and requires dedicated software tools compared to unidimensional parameters, which is disadvantageous in an emergency setting.

Midregional pro-atrial natriuretic peptide is a useful indicator for the detection of impaired left ventricular function in patients with coronary artery disease.

AIMS: We compared the diagnostic performance of N-terminal pro-brain natriuretic peptide (NT-proBNP) with a newly developed assay for the midregional part of pro-atrial natriuretic peptide (MR-proANP) concerning the detection of impaired left ventricular ejection function (LVEF) among patients with coronary artery disease (CAD). METHODS AND RESULTS: Plasma levels of MR-proANP and NT-proBNP were determined in 102 consecutive patients with a history of ST-elevation myocardial infarction. Plasma levels of both markers were measured during a mean follow-up period of 687 days after acute myocardial infarction. Univariate analyses revealed inverse correlations between MR-proANP levels and LVEF (r=-0.39; p<0.001), NT-proBNP levels and LVEF (r=-0.39; p<0.001) and a positive correlation between MR-proANP and NT-proBNP (r=0.75; p<0.001). After adjustment for traditional risk factors, MR-proANP was the strongest predictor for LVEF (p=0.001) in multivariate analysis, being even superior to NT-proBNP. The area under the ROC curve (AUC) indicated moderate performance (AUC=0.73; p<0.01) of MR-proANP regarding the detection of a reduced LVEF<50%. The AUC of NT-proBNP for detection of impaired LVEF<50% was 0.68 (p=0.019). The negative predictive values of both markers were 86% for MR-proANP at a cut-off >135 pmol/L and NT-proBNP at a cut-off >560 pmol/L. At these cut-offs, the specificity of MR-proANP was 90%, and the specificity of NT-proBNP was 84%. CONCLUSIONS: MR-proANP is a useful indicator for the exclusion of a preserved left ventricular function in patients with coronary artery disease. The study demonstrates that the diagnostic performance of MR-proANP is comparable to the "gold standard" NT-proBNP.

High plasma levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8) characterize patients prone to ventricular fibrillation complicating myocardial infarction.

BACKGROUND: Atherosclerotic plaques prone to cause thrombotic complications and plaque rupture account for the majority of fatal myocardial infarctions (MI), which may be complicated by ventricular fibrillation (VF). Matrix-degrading metalloproteinases (MMPs) and their inhibitors (TIMPs) are expressed in atherosclerotic lesions and contribute to plaque vulnerability. Interleukin-8 (IL-8) is one of the predominant chemokines interacting with MMPs and TIMPs and the coagulation system. The aim of the present study was to assess potential differences of levels of MMP-9, TIMP-1 and IL-8 in postmyocardial infarction patients with or without VF complicating acute MI. METHODS: Blood samples were taken from 45 patients with VF complicating acute MI and from 88 patients without VF. All samples were collected during a symptom-free interval remote from the acute ischemic event with a median of 556 days. The markers of interest were TIMP-1, MMP-9 and IL-8. RESULTS: IL-8 and TIMP-1 levels were significantly higher among patients with VF than among patients without VF (p<0.001). In a logistic regression approach IL-8 was an independent indicator of patients prone to VF during MI (p=0.03). High levels of TIMP-1 (p=0.05), MMP-9 (p=0.03), the MMP-9/TIMP-1 ratio (p=0.049) and hypertension (p=0.02) were found to be indicators in patients with reinfarction or unstable angina pectoris during follow-up. Hypertension (p=0.02) and MMP-9 (p=0.03) were the only significant indicators characterizing patients undergoing coronary reinterventions, such as percutaneous coronary interventions and coronary bypass surgery. CONCLUSIONS: Higher TIMP-1 and IL-8 levels are present in patients with VF complicating MI. High TIMP-levels may be related to the degree of fibrosis which is a substrate for electrical instability and may contribute to the occurrence of VF. Patients prone to develop VF during MI seem to have an increased proinflammatory condition compared to patients without VF.

Volumetric assessment of epicardial adipose tissue with cardiovascular magnetic resonance imaging.

OBJECTIVE: Previous studies determined the amount of epicardial fat by measuring the right ventricular epicardial fat thickness. However, it is not proven whether this one-dimensional method correlates well with the absolute amount of epicardial fat. In this prospective study, a new cardiovascular magnetic resonance imaging (CMR) method using the three-dimensional summation of slices method was introduced to assess the total amount of epicardial fat. RESEARCH METHODS AND PROCEDURES: CMR was performed in 43 patients with congestive heart failure and in 28 healthy controls. The absolute amount of epicardial fat was assessed volumetrically in consecutive short-axis views by means of the modified Simpson's rule. Additionally, the right ventricular epicardial fat thickness was measured in two different imaging planes: long-axis view (EFT-4CV) and consecutive short-axis views (EFT-SAX). RESULTS: Using the volumetric approach, patients with congestive heart failure had less epicardial fat mass than controls (51 g vs. 65 g, p=0.01). This finding was supported by EFT-SAX (2.9 mm vs. 4.3 mm, p<0.0001) but not by EFT-4CV (3.5 mm vs. 3.8 mm, p=not significant). Epicardial fat mass correlated moderately with EFT-SAX in both groups (r=0.466, p=0.012 in controls and r=0.590, p<0.0001 in patients) and with EFT-4CV in controls (r=0.387, p=0.042). There were no significant differences between EFT-4CV and EFT-SAX in controls (4.3 mm vs. 3.8 mm, p=0.240). However, in the heart failure group, EFT-4CV was significantly higher compared with EFT-SAX (3.5 mm vs. 2.9 mm, p=0.003). Interobserver variability and reproducibility were superior for the volumetric approach compared with thickness measurements. DISCUSSION: Quantitative assessment of epicardial fat mass using the CMR-based volumetric approach is feasible and yields superior reproducibility compared with conventional methods.

Assessment of markers of thrombin generation in patients with acute myocardial infarction complicated by ventricular fibrillation.

BACKGROUND: In most cases, sudden cardiac death is triggered by ischemia-related ventricular tachyarrhythmias and accounts for 50% of deaths from cardiovascular disease in developed countries. Chronic elevation of indicators of coagulation activation has been found in patients with coronary heart disease, but a role of coagulation activation as a potential risk factor for ventricular fibrillation (VF) during acute myocardial infarction (MI) has not been investigated. METHODS: We enrolled 50 patients with a history of MI, of whom 26 presented with VF in the acute phase of myocardial ischemia; 24 patients had an acute MI without ventricular tachyarrhythmias. Levels of thrombin-antithrombin complexes (TAT), prothrombin fragment F1 + 2 (F1 + 2), fibrinopeptide A (FPA), plasmin-antiplasmin complexes (PAP), protein C, antithrombin, activated partial thromboplastin time (aPTT), thromboplastin time, D-Dimer, fibrinogen, and high-sensitivity C-reactive protein (hs-CRP) were measured in plasma samples of all patients. Blood collection was obtained sequentially in two separate settings. Patients were studied at a median of 351 days after the acute coronary event. RESULTS: Higher levels of TAT complexes (13.4 +/- 22.2 vs. 3.03 +/- 4.3 microg/l; p = 0.02), FPA (79.7 +/- 132.3 vs. 24.04 +/- 41.3 ng/ml; p = 0.04), and F1+2 (1.89 +/- 1.3 vs. 1.16 +/- 0.5 nmol/l; p = 0.01) were observed in patients with VF compared with patients without ventricular tachyarrhythmias during the acute phase of MI. D-Dimer levels displayed a trend without reaching statistical significance (0.69 +/- 0.48 vs. 0.48 +/- 0.24 mg/l; p = 0.06). No differences were found in hs-CRP (3.25 +/- 4.5 vs. 4.4 +/- 8.8 mg/l; p = 0.5) and fibrinogen (2.8 +/- 0.9 vs. 2.7 +/- 0.9 g/l; p = 0.6) measurements. Repeat assessment of markers of coagulation activation at a median of 847 days revealed a highly significant decrease in patients with VF. CONCLUSIONS: Markers of thrombin generation are transiently increased in patients with VF during the acute phase of MI. These findings have implications for risk assessment and genetic screening of patients prone to VF during acute myocardial ischemia.

Utility of combined parameters of common carotid intima-media thickness or albuminuria in diagnosis of coronary artery disease in women.

BACKGROUND: Noninvasive testing for suspected coronary artery disease is challenging. We prospectively investigated whether measurements of carotid intima-media thickness in the presence or absence of albuminuria in patients with stable chest pain syndromes can be used as a noninvasive test algorithm for prediction of significant coronary artery disease. Additionally, this algorithm was tested with regard to gender differences. METHODS: Consecutive patients (79 men and 72 women) with stable chest pain syndromes and suspected coronary artery disease admitted for coronary angiography were studied. Measurements of intima-media thickness were performed by ultrasound. Urinary albumin excretion was measured in a random urine specimen. A positive test for coronary artery disease was defined as an intima-media thickness >or=1 mm or albuminuria. RESULTS: Sensitivity, specificity and positive likelihood ratio for a combination of intima-media thickness values >or=1 mm or presence of albuminuria to predict coronary artery disease were, respectively, 0.5, 0.73 and 1.27 in men and 0.68, 0.79 and 3.32 in women. Sensitivity, specificity and positive likelihood ratio for exercise ECG were, respectively, 0.54, 0.48 and 1.08 in men and 0.47, 0.45 and 0.8 in women. CONCLUSIONS: Intima-media thickness of the common carotid artery or presence of albuminuria are clinically valuable parameters in the noninvasive diagnostic work up of women with stable chest pain syndromes. Their value is limited in men.

A novel regional right ventricular wall-motion abnormality observed in a case of acute pulmonary embolism (reverse McConnell sign).

Among various echocardiographic parameters for diagnosis of pulmonary embolism, an abnormal regional contraction pattern of the right ventricular free wall consisting of normokinesia of the apical segment and akinesia of the midfree wall with persistence of abnormal wall motion at the base has proved to be fairly specific for pulmonary embolism. This echocardiographic abnormality has been termed "McConnell sign." We describe the case of a patient with acute pulmonary embolism who developed reversible akinesia of the apex and right ventricular midfree wall, a finding we would like to term "reverse McConnell sign."

Time course of systemic markers of inflammation in patients presenting with acute coronary syndromes.

Inflammation within coronary plaques may cause an acute coronary syndrome by promoting rupture and erosion. It was the aim of this study to examine whether markers of inflammation derive from a cardiac or extracardiac source and how their levels develop over time. Blood samples were taken from patients with acute coronary syndromes (ACS) with proven atherosclerotic lesion(s) of the left coronary artery (n=13) and from control patients without coronary artery disease (n=13). Blood was taken from the femoral vein and the coronary sinus vein before and after coronary angioplasty (day 0) and on days 1 and 120. Levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1-receptor antagonist (IL-1 ra) and soluble CD40 ligand (sCD40L) were higher in ACS patients as compared to controls and remained elevated up to day 120. In the long-term time course these markers of inflammation and plaque remodeling slightly decreased in ACS patients. There were no statistically significant differences detectable in the levels of TNF-alpha, IL-6, IL-1 beta, IL-10, IL-1 ra, sCD40L and monocyte chemoattractant protein-1 (MCP-1) in the blood of ACS patients taken from a cardiac source as compared to an extracardiac source (coronary sinus vs. femoral vein). This study demonstrates the importance of a systemic inflammatory condition in patients with ACS, in whom markers of inflammation are increased as compared to controls. During long-term follow-up the pro-inflammatory activity remains elevated in ACS patients, supporting the concept of a systemic rather than a local vascular inflammation contributing to the development of atherosclerosis.

Markers of myocardial damage, tissue healing, and inflammation after radiofrequency catheter ablation of atrial tachyarrhythmias.

INTRODUCTION: Radiofrequency ablation produces a localized endomyocardial necrosis that may result in release of biochemical markers reflecting myocardial cell damage, inflammation, and tissue reparation. The aim of this study was to determine the extent of rise and time course of markers of inflammation and tissue reparation in patients undergoing radiofrequency catheter ablation. METHODS AND RESULTS: Serial blood samples were taken from patients with AV nodal reentrant tachycardia (n = 5), Wolff-Parkinson-White syndrome (n = 3), and atrial flutter (n = 5) undergoing radiofrequency ablation. Blood was taken before ablation (day 0, baseline) and at day 1 and day 120 after ablation. The proinflammatory marker interleukin-6 (IL-6), troponin I (TNI), and myoglobin, as well as matrix metalloproteinase-9 (MMP-9), a marker for myocardial healing, were measured by enzyme-linked immunosorbent assay. Levels of IL-6, TNI, myoglobin, and MMP-9 were significantly elevated on day 1 after ablation compared to baseline levels. Seven of the 13 patients had troponin levels greater than the threshold of significant myocardial damage (>0.1 ng/mL) on day 1. Plasma levels of MMP-9 were still elevated on day 120 compared to values before ablation (P = 0.021). CONCLUSION: Markers of inflammation, wound healing, and myocardial damage are increased in patients who undergo radiofrequency ablation. Levels of MMP-9, a marker for myocardial healing and repair, are still elevated 120 days after the procedure, suggesting that radiofrequency ablation induces tissue damage leading to a long-term process of reparation.