Epicardial Adipose Tissue Is Associated with Plaque Burden and Composition and Provides Incremental Value for the Prediction of Cardiac Outcome. A Clinical Cardiac Computed Tomography Angiography Study.

OBJECTIVES: We sought to investigate the association of epicardial adipose tissue (eCAT) volume with plaque burden, circulating biomarkers and cardiac outcomes in patients with intermediate risk for coronary artery disease (CAD). METHODS AND RESULTS: 177 consecutive outpatients at intermediate risk for CAD and completed biomarker analysis including high-sensitive Troponin T (hs-TnT) and hs-CRP underwent 256-slice cardiac computed tomography angiography (CCTA) between June 2008 and October 2011. Patients with lumen narrowing ≥50% exhibited significantly higher eCAT volume than patients without any CAD or lumen narrowing <50% (median (interquartile range, IQR): 108 (73-167) cm3 vs. 119 (82-196) cm3, p = 0.04). Multivariate regression analysis demonstrated an independent association eCAT volume with plaque burden by number of lesions (R2 = 0.22, rpartial = 0.29, p = 0.026) and CAD severity by lumen narrowing (R2 = 0.22, rpartial = 0.23, p = 0.038) after adjustment for age, diabetes mellitus, hyperlidipemia, body-mass-index (BMI), hs-CRP and hs-TnT. Univariate Cox proportional hazards regression analysis identified a significant association for both increased eCAT volume and maximal lumen narrowing with all cardiac events. Multivariate Cox proportional hazards regression analysis revealed an independent association of increased eCAT volume with all cardiac events after adjustment for age, >3 risk factors, presence of CAD, hs-CRP and hs-TnT. CONCLUSION: Epicardial adipose tissue volume is independently associated with plaque burden and maximum luminal narrowing by CCTA and may serve as an independent predictor for cardiac outcomes in patients at intermediate risk for CAD.

Reference values for left and right ventricular trabeculation and non-compacted myocardium.

BACKGROUND: Since the differentiation between physiological and pathological trabeculation is challenging, we assessed its distribution in a reference population of selected healthy volunteers. METHODS: We studied 117 subjects (58 males) stratified into age tertiles and by gender. Cardiovascular magnetic resonance images were acquired using a standard SSFP-sequence. Left and right ventricular (LV/RV) end-diastolic (EDV), end-systolic (ESV) and trabeculated volumes indexed to the body surface area as well as ejection fraction (EF) were quantified in short-axis views. The maximum non-compacted-to-compacted (NC/C) ratio was measured in long-axis views. RESULTS: The trabeculated volumes were significantly larger in men than in women and decreased with age. The correlation between both was moderate (r=0.46; p<0.001). LV trabeculated volume was positively associated with EDV and ESV (r=0.74; r=0.59; both p<0.001) and negatively with EF (r=-0.27; p<0.005). It was no independent predictor for EF. The maximum NC/C ratio was >2.3 in 46.2% and >2.5 in 37.6% of the subjects, which is regarded as abnormal in current literature. The fraction of subjects with a maximum NC/C ratio >2.3 and the mean maximum NC/C ratio differed significantly between gender but not between age groups. An increasing NC/C ratio was associated with a significant decrease in EF (r=-0.21; p<0.05). CONCLUSION: A considerable amount of healthy volunteers fulfils the current diagnostic criteria of LV noncompaction with female subjects showing a higher fraction of false-positive results than males. LV trabeculated volume is more pronounced in young subjects and declines with age. The use of age- and gender-specific reference values as provided in this study may facilitate the delineation of physiological and pathological findings.

Selective apheresis of C-reactive protein: a new therapeutic option in myocardial infarction?

BACKGROUND: There is substantial evidence that C-reactive protein (CRP) mediates secondary damage of the myocardium after acute myocardial infarction (AMI). The aim of this animal trial in pigs was to specifically deplete CRP from porcine plasma after AMI and to study possible beneficial effects of the reduced CRP concentration on the infarcted area. METHODS: Ten pigs received balloon catheter-induced myocardial infarction. CRP was depleted from five animals utilizing a new specific CRP-adsorber, five animals served as controls. The area of infarction was analyzed by cardiovascular magnetic resonance imaging on day 1 and day 14 after AMI. Porcine CRP levels were determined by ELISA. RESULTS: CRP-apheresis resulted in a mean reduction of the CRP levels up to 48.3%. The area of infarction was significantly reduced by 30 ± 6% (P = 0.003) within 14 days in the treatment group, whereas it increased by 19 ± 11% (P = 0.260) in the controls. Fourteen days after infarction, the infarcted area revealed compact, transmural scars in the controls, whereas animals receiving CRP-apheresis showed spotted scar morphology. In the interventional group, a significantly higher left ventricular ejection fraction (LVEF) was observed after 14 days as compared to the controls (57.6 ± 2.4% vs. 46.4 ± 2.7%; P = 0.007). CONCLUSIONS: In a pig model for AMI, we observed that selective CRP-apheresis significantly reduces CRP levels and the volume of the infarction zone after AMI. Additionally, it changes the morphology of the scars and preserves cardiac output (LVEF).

Classification of diastolic function with phase-contrast cardiac magnetic resonance imaging: validation with echocardiography and age-related reference values.

OBJECTIVES: To investigate whether cardiac magnetic resonance phase-contrast imaging (PC-CMR) can determine left ventricular (LV) diastolic function in comparison to echocardiography (EC). BACKGROUND: Non-invasive evaluation of diastolic function is important for the diagnostic classification and risk stratification of patients with cardiomyopathies. With EC, diastolic function is classified based on the mitral blood flow, LV myocardial tissue Doppler velocities and pulmonary venous flow. PC-CMR has the potential to measure these parameters and may be an important tool to assess diastolic function in clinical routine. METHODS: In 36 patients with various cardiovascular diseases and 6 healthy volunteers, we performed single-slice short-axis PC-CMR at the level of the mitral leaflet tip and the inflow of the pulmonary veins to generate EC-comparable mitral E and A waves, septal and lateral e' and a' tissue velocities, and E/A and E/e' ratios. EC was performed after PC-CMR in all patients and six volunteers. Patients were classified into three groups of DD for both techniques. In addition, we evaluated 120 healthy volunteers as controls (3 age groups: 1 = 20-35 years; 2 = 36-50 years; 3 ≥ 51 years) for reference values. RESULTS: PC-CMR correlation with EC regarding the relation of mitral E and A velocities was good (r = 0.83, p < 0.001). The correlation for the mean septal and lateral E/e' ratio was high with r = 0.90 (p < 0.001). 40/42 subjects (95 %) were categorized correctly. The mean scan time for PC-CMR was 189 ± 16 s and mean analysis time was 348 ± 95 s. EC image acquisition time was slightly higher (201 ± 37 s, p = n.s.), whereas EC image analysis time was significantly lower (149 ± 23 s, p < 0.001). CONCLUSION: The classification of DD with PC-CMR is feasible and shows good agreement with the widely accepted EC classification of DD. We present a practical approach for the clinically important assessment of DD with PC-CMR, circumventing sophisticated and time-consuming CMR sequences and specially designed software analysis tools.

Giant Dilatation of the Right Coronary Aortic Bulb with Compression of the Right Ventricular Outflow Tract Mimicking a Ventricular Septal Defect: Diagnostic workup Using Echocardiography, Heart Catheterization, and Cardiac Computed Tomography.

Annuloaortic ectasia is a relatively rare diagnosis. Herein, we report an unusual case of an annuloaortic ectasia with asymmetric dilatation of the right coronary bulb mimicking a membranous ventricular septal defect (VSD) with Eisenmenger reaction by transthoracic echocardiography. Aortic angiography showed a dilated aortic root and moderate aortic regurgitation. Right cardiac catheterization, on the other hand, exhibited normal pulmonary artery blood pressure and normal pulmonary resistance, whereas normal venous gas values were measured throughout the caval vein and the right atrium, excluding relevant left-right shunting. Further diagnostic workup by cardiac computed tomography angiography (CCTA) unambiguously illustrated the asymmetric geometry of the ectatic aortic cusp and root causing compression of the right heart and of the right ventricular (RV) outflow tract. After review of echocardiographic acquisitions, the blood flow detected between the left and right ventricles (mimicking VSD) was interpreted as turbulent inflow from the left ventricle into the ectatic right coronary cusp. Furthermore, elevated pulmonary artery blood pressure measured by echocardiography was attributed to "functional pulmonary stenosis" due to compression of the RV outflow tract by the aorta, as demonstrated by CCTA.

Conservatively treated incidental aneurysm of the distal left main coronary artery: detection by coronary angiography and noninvasive followup using coronary computed tomography angiography.

Coronary artery aneurysms are relatively rare and commonly associated with significant coronary artery disease (CAD), inflammatory diseases (Kawasaki syndrome, infection), or iatrogenic complications. Herein, we report an unusual case of an incidental coronary aneurysm of the left main artery in a patient without specific clinical symptoms of myocardial ischemia or systemic inflammation and without angiographically significant CAD. Angiographic images are provided, acquired during cardiac catheterization, as well as coronary computed tomography angiography (CCTA) images obtained at 1 year of followup.

Prediction of life-threatening arrhythmic events in patients with chronic myocardial infarction by contrast-enhanced CMR.

OBJECTIVES: We hypothesized that infarct transmurality assessed with late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) predicts arrhythmic events in patients with chronic myocardial infarction. BACKGROUND: Patients with decreased left ventricular function due to chronic myocardial infarction are at increased risk for life-threatening arrhythmias related to infarcted tissue. LGE-CMR accurately detects infarct morphology. METHODS: We prospectively enrolled 52 patients with chronic myocardial infarction referred for primary preventive implantable cardioverter-defibrillator (ICD) implantation following MADIT (Multicenter Automatic Defibrillator Implantation Trial) study criteria. Using LGE-CMR, left ventricular volumes, function, and infarct morphology were assessed including calculation of total and relative infarct mass, infarct border, infarct border zone, and infarct transmurality. RESULTS: Patients were followed for 1,235 ± 341 days. The primary combined endpoint including appropriate device therapy (ICD discharge or antitachycardia pacing) or death from cardiac cause occurred in 16 individuals resulting in an annual event rate of 4.7%. Six patients received an appropriate shock, 7 patients received recurrent appropriate antitachycardia pacing for sustained ventricular tachycardia, and 3 patients died of cardiac cause. There was a significant association to relative infarct mass (38 ± 8% vs. 28 ± 14%, p = 0.02), infarct transmurality (24 ± 8 g vs. 16 ± 12 g, p = 0.02), and relative infarct transmurality (RIT) (63 ± 12% vs. 48 ± 23%, p = 0.01). In separate logistic regression models, no variable emerged as significant when combined with RIT. As a single effect, RIT emerged as a predictor of the primary endpoint (p = 0.02). A RIT cutoff at 43% resulted in a sensitivity of 88%, a specificity of 50%, a positive predictive value of 44%, and a negative predictive value of 90%. CONCLUSIONS: In patients with chronic myocardial infarction scheduled for primary preventive ICD implantation, infarct transmurality as defined by LGE-CMR identifies a subgroup with increased risk for life-threatening arrhythmias and cardiac death.

Prognostic impact of T2-weighted CMR imaging for cardiac amyloidosis.

OBJECTIVES: Using cardiac magnetic resonance imaging (MRI) we tested the diagnostic value of various markers for amyloid infiltration. METHODS: We performed MRI at 1.5 T in 36 consecutive patients with cardiac amyloidosis and 48 healthy volunteers. The protocol included cine imaging, T2-weighted spin echo, T1-weighted spin echo before and early after contrast and late gadolinium enhancement. We compared the frequency of abnormalities and their relation to mortality. RESULTS: Median follow-up was 31 months. Twenty-three patients died. Mean left ventricular (LV) mass was 205 ± 70 g. LV ejection fraction (EF) was 55 ± 12%. T2 ratio was 1.5 ± 0.4. 33/36 patients had pericardial and 22/36 had pleural effusions. All but two had heterogeneous late enhancement. Surviving patients did not differ from those who had died with regard to gender, LV mass or volume. Surviving patients had a significantly higher LVEF (60.4 ± 9.9% vs. 51.6 ± 11.5%; p = 0.03). The deceased patients had a lower T2 ratio than those who survived (1.38 ± 0.42 vs. 1.76 ± 0.17; p = 0.005). Low T2 was associated with shorter survival (Chi-squared 11.3; p < 0.001). Cox regression analysis confirmed T2 ratio < 1.5 as the only independent predictors for survival. CONCLUSION: Cardiac amyloidosis is associated with hypointense signal on T2-weighted images. A lower T2 ratio was independently associated with shortened survival.

A new approach towards improved visualization of myocardial edema using T2-weighted imaging: a cardiovascular magnetic resonance (CMR) study.

PURPOSE: To compare T2-weighted cardiovascular magnetic resonance (CMR) imaging with AASPIR (asymmetric adiabatic spectral inversion recovery) and STIR (short T1 inversion recovery) for myocardial signal intensity, image quality, and fat suppression. MATERIALS AND METHODS: Forty consecutive patients (47 ± 16 years old) referred by cardiologists for CMR-based myocardial tissue characterization were scanned with both STIR and AASPIR T2-weighted imaging approaches. Signal intensity of left ventricular myocardium was normalized to a region of interest generating a signal-to-noise ratio (SNR). In six patients with regional edema on STIR the contrast-to-noise ratio (CNR) was assessed. Two independent observers used a scoring system to evaluate image quality and artifact suppression. Six healthy volunteers (three males, 32 ± 7 years) were recruited to compare fat suppression between AASPIR and STIR. RESULTS: SNR of AASPIR was greater than STIR for basal (128 ± 44 vs. 83 ± 40, P < 0.001), mid- (144 ± 65 vs. 96 ± 39, P < 0.01), and apical (145 ± 59 vs. 105 ± 35, P < 0.05) myocardium. Improved image quality and greater suppression of artifacts was demonstrated with AASPIR. In patients with regional edema, CNR increased by 49% with AASPIR, while SNR of pericardial fat did not differ (44 ± 39 vs. 33 ± 30, P > 0.05). CONCLUSION: Our findings support the implementation of an AASPIR-based approach for T2-weighted imaging due to improved pericardial fat suppression, image quality, and artifact suppression with greater CNR and SNR.

Specific removal of C-reactive protein by apheresis in a porcine cardiac infarction model.

BACKGROUND: C-reactive protein (CRP) is a possible causative factor of the destructive processes observed during the weeks after myocardial infarction. METHODS: We developed a clinically relevant animal model including the removal of CRP from blood plasma utilizing a specific CRP adsorber and the visualization of the infarct scar in the living animal by cardiovascular magnetic resonance imaging as a tool to investigate the impact of CRP after acute myocardial infarction. RESULTS: We describe the facets of this model system and kinetics of clinical blood parameters like CRP and troponin. In addition, we demonstrate the potency of CRP apheresis reducing CRP levels by ~70% in the established treatment system. CONCLUSION: We showed for the first time that it is possible to conduct apheresis at the following 2 days after acute myocardial infarction in a porcine infarction model and to analyze the infarct by cardiovascular magnetic resonance imaging at day 1 and 14.

An open-source software tool for the generation of relaxation time maps in magnetic resonance imaging.

BACKGROUND: In magnetic resonance (MR) imaging, T1, T2 and T2* relaxation times represent characteristic tissue properties that can be quantified with the help of specific imaging strategies. While there are basic software tools for specific pulse sequences, until now there is no universal software program available to automate pixel-wise mapping of relaxation times from various types of images or MR systems. Such a software program would allow researchers to test and compare new imaging strategies and thus would significantly facilitate research in the area of quantitative tissue characterization. RESULTS: After defining requirements for a universal MR mapping tool, a software program named MRmap was created using a high-level graphics language. Additional features include a manual registration tool for source images with motion artifacts and a tabular DICOM viewer to examine pulse sequence parameters. MRmap was successfully tested on three different computer platforms with image data from three different MR system manufacturers and five different sorts of pulse sequences: multi-image inversion recovery T1; Look-Locker/TOMROP T1; modified Look-Locker (MOLLI) T1; single-echo T2/T2*; and multi-echo T2/T2*. Computing times varied between 2 and 113 seconds. Estimates of relaxation times compared favorably to those obtained from non-automated curve fitting. Completed maps were exported in DICOM format and could be read in standard software packages used for analysis of clinical and research MR data. CONCLUSIONS: MRmap is a flexible cross-platform research tool that enables accurate mapping of relaxation times from various pulse sequences. The software allows researchers to optimize quantitative MR strategies in a manufacturer-independent fashion. The program and its source code were made available as open-source software on the internet.

Aortic dilatation in patients with prosthetic aortic valve: comparison of MRI and echocardiography.

BACKGROUND AND AIM OF THE STUDY: Patients with prosthetic aortic valve have an increased risk for aortic dissection, which rises further with growing aortic diameters. Thus, accurate aortic monitoring is required. As transthoracic echocardiography (TTE), the current clinical standard, is frequently restricted to the proximal ascending aorta, the use of two-dimensional cardiovascular magnetic resonance (2D-CMR) in transverse orientation was investigated as a screening tool to assess ascending aortic dimensions. METHODS: Fast, non-contrast-enhanced, non-breath-hold, steady-state free-precession (SSFP) sequences (1.5 Tesla, slice thickness 7 mm, gap 1.8 mm, scan time 10-15 s) were applied to image the thorax in transverse planes. To test the accuracy of aortic dimensions obtained in this way, comparison was made to contrast-enhanced three-dimensional MR angiography (3D-MRA) as the 'gold standard' in 30 patients with aortic or aortic valve disease. After validation, transverse 2D-CMR was used to assess ascending aortic dimensions in 65 patients with aortic bioprostheses, and the results were compared to those acquired with TTE. RESULTS: Data acquired with both 2D-CMR and 3D-MRA agreed well when assessing ascending aortic diameters (r = 0.99; p < 0.001; mean difference 0.1 +/- 0.1 cm). In patients with bioprostheses, the image quality was diagnostic in 100% of cases for 2D-CMR, and in 93.4% for TTE. The ascending aortic diameter by 2D-CMR (mean 3.8 +/- 0.5 cm; range: 2.6-5.0 cm) was larger (p < 0.001) than by TTE (3.3 +/- 0.6 cm; range: 2.3-4.9 cm). Aortic dilatation (diameter, indexed by body surface area, > 2.1 cm/m2) was present in 38.5% of 2D-CMR cases and in 11.5% of TTE cases. The intra- and inter-observer variabilities to assess aortic dimensions by 2D-CMR were 2.1 +/- 1.9% and 4.3 +/- 3.7%, respectively. CONCLUSION: Imaging of the complete thorax in transverse orientation using fast, non-contrast-enhanced SSFP images provided an accurate and reliable approach to screen for aortic dilatation. In patients with aortic bioprostheses, 2D-CMR revealed a high prevalence of aortic dilatation, which was considerably underestimated by TTE.

The use of cardiovascular magnetic resonance in acute myocardial infarction.

Acute myocardial infarction (MI) results in reversible and irreversible injury to the myocardium, including stunning, edema, myocyte necrosis, and microvascular obstruction. Because of its unique tissue characterization capabilities, cardiovascular magnetic resonance provides a reliable means of visualizing and quantifying the extent of these injuries. Such characterization is readily achieved through a comprehensive examination including function, first-pass perfusion, T2 (edema), and late enhancement imaging sequences. This helps to predict the prognosis, assess the success of reperfusion, detect acute phase complications, localize the area of the acute event, and confirm the diagnosis in clinical scenarios with clinical presentations similar to that of acute MI. Finally, one emerging application is the role cardiovascular magnetic resonance (CMR) may play in detecting some infarcts very early on in their evolution. This article covers the established and emerging clinical applications of CMR in the settings of reperfused and nonreperfused infarcts and in acute myocardial ischemia, the step immediately preceding actual irreversible injury.

Acute oedema in the evaluation of microvascular reperfusion and myocardial salvage in reperfused myocardial infarction with cardiac magnetic resonance imaging.

UNLABELLED: The accurate measurement of myocardial salvage is critical to the ongoing refinement of reperfusion strategies in acute myocardial infarction (AMI). Cardiac magnetic resonance imaging (CMR) can define the area at risk in AMI by the presence of myocardial oedema, identified by high signal intensity on T(2)-weighted imaging with a short inversion time inversion-recovery (STIR) sequence. In addition, myocardial necrosis can be identified with CMR delayed contrast enhanced imaging. In this prospective study we examined the relationship of acute oedema and necrosis with impaired microvascular reperfusion. We also evaluated acute oedema as a marker of the area at risk in AMI, for the purposes of documenting myocardial salvage. CMR was performed on 15 patients with (AMI), within 24h of successful percutaneous coronary intervention (PCI). Left ventricular (LV) systolic dysfunction was defined by a systolic thickening <40% (severe <20%). Microvascular reperfusion was evaluated during the acute phase of contrast wash-in. CMR was repeated 3 months post-PCI to evaluate recovery of LV function and final infarct size. Myocardial salvage was defined as the percentage of the area at risk that was not infarcted on follow up CMR. There was a significant correlation between impaired microvascular reperfusion and the extent of segmental oedema (R=0.363, P<0.01), but not myocardial necrosis (R=0.110, P>0.5). The extent of myocardial salvage correlated with recovery of systolic function (R=0.241, P<0.05), which was strongest in LV segments with severely reduced systolic function (R=0.422, P<0.01). CONCLUSIONS: In acutely reperfused AMI, oedema can be used to identify the area at risk for the purpose of calculating myocardial salvage. The correlation between myocardial oedema and reperfusion status suggests a pathological role of acute oedema in the impairment of microvascular reperfusion.

Takotsubo cardiomyopathy after nasal application of epinephrine--a magnetic resonance study.

Takotsubo cardiomyopathy (TTC), which is characterized by transient left ventricular impairment in absence of coronary artery disease, is usually associated with emotional or physical stress, supposing that catecholamines are involved in pathophysiology. The present article reports on two cases with characteristic features of TTC following nasal application of epinephrine during nasal surgery. Both subjects serially underwent cardiovascular magnetic resonance, which revealed myocardial vasodilatation, capillary leak and regional edema in the acute state and ruled out focal necrosis. Thus, the present cases both stress the catecholamine hypothesis in the pathogenesis of TTC and underline the potential of CMR to diagnose and monitor TTC.

Feasibility of cardiovascular magnetic resonance to assess the orifice area of aortic bioprostheses.

BACKGROUND: Prosthetic orifice area, usually calculated by transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE), provides important information regarding the hemodynamic performance of aortic bioprostheses. However, both TTE and TEE have limitations; therefore accurate and reproducible determination of the orifice area often remains a challenge. The present study aimed to investigate the feasibility of cardiovascular magnetic resonance (CMR) to assess the orifice areas of aortic bioprostheses. METHODS AND RESULTS: CMR planimetry of the orifice area was performed in 65 patients (43/22 stented/stentless prostheses; mean time since implantation, 3.1+/-2.8 years; mean orifice area [TTE], 1.70+/-0.43 cm(2); 62 normally functioning prostheses, 2 severe stenoses, and 1 severe regurgitation) in an imaging plane perpendicular to the transprosthetic flow using steady-state free-precession cine imaging under breath-hold conditions on a 1.5-T MR system. CMR results were compared with TTE (continuity equation, n=65) and TEE (planimetry, n=31). CMR planimetry was readily feasible in 80.0%; feasible with limitation in 15.4% because of stent, flow, and sternal wire artifacts; and impossible in 4.6% because of flow artifacts. Correlations of the orifice areas by CMR with TTE (r=0.82) and CMR with TEE (r=0.92) were significant. The average difference between the methods was -0.02+/-0.24 cm(2) (TTE) and 0.05+/-0.15 cm(2) (TEE). Agreement was present for stented and stentless devices and independent of orifice size. Intraobserver and interobserver variabilities of CMR planimetry were 6.7+/-5.4% and 11.5+/-7.8%. CONCLUSIONS: The assessment of aortic bioprostheses with normal orifice areas by CMR is technically feasible and provides orifice areas with a close correlation to echocardiography and low observer dependency.