The First Year of Noninvasive Remote Telemonitoring in Chronic Heart Failure Is not Cost Saving but Improves Quality of Life: The Randomized Controlled CardioBBEAT Trial.

Introduction: Remote telemonitoring (RTM) for patients with chronic heart failure (HF) holds promise to improve prognosis and well-being beyond the standard of care (SoC). The CardioBBEAT trial assessed the health economic and clinical impact of an interactive bidirectional RTM system (Motiva®) versus SoC for patients with HF and a reduced ejection fraction (HFrEF), in Germany. Methods: This multicenter, randomized controlled trial enrolled 621 patients with HFrEF (mean age 63.0 ± 11.5 years, 88% men). The primary endpoint was the integrated effect of the intervention on total costs and nonhospitalized days alive after 12 months, reported as incremental cost-effectiveness ratio (ICER). Costs (in k€) were based on actual charges of patients' statutory health insurance. Among secondary outcome measures were mortality and disease-specific quality of life. Results: We found a neutral effect on nonhospitalized days alive (RTM mean 341 ± 59 days, SoC 346 ± 45 days; p = 0.298) associated with increased total costs (RTM 18.5 ± 39.5 k€, SoC 12.8 ± 22.0 k€; p = 0.046). This yielded an ICER of -1.15 k€/day. RTM did not impact mortality risk. All quality of life scales were consistently and meaningfully improved in the RTM group at 12 months compared to SoC (all p < 0.01). Conclusions: The first 12 months of RTM were not cost-effective compared to SoC in patients with HFrEF, but associated with a relevant improvement in disease-specific quality of life. The balanced assessment of the potential benefit of RTM requires integration of both the societal and patient perspective. ClinTrials.gov (NCT02293252).

Authorship: from credit to accountability. Reflections from the Editors' Network.

The Editors' Network of the European Society of Cardiology provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors' Network.

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship- emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors' Network of the European Society of Cardiology.

High-dose dobutamine stress steady-state free precession (SSFP) cine MRI at 3T with patient adaptive local radiofrequency (RF) shimming using dual-source RF transmission.

PURPOSE: To prospectively assess the feasibility, image quality, and diagnostic accuracy of high-dose dobutamine stress magnetic resonance imaging (DSMR) using steady-state free precession (SSFP) cine imaging at 3T applying a dual-source radiofrequency (RF) excitation magnetic resonance imaging (MRI) system with parallel transmission and patient adaptive local RF shimming. MATERIALS AND METHODS: DSMR using SSFP cine imaging was performed in 44 patients at 3T scheduled for a clinically indicated coronary angiography. The effect of conventional versus dual-source RF transmission was assessed regarding homogeneity of the B1 field, contrast-to-noise ratios (CNRs) at rest, image quality, and diagnostic accuracy of DSMR using long and short axis. RESULTS: The mean percentage of the intended flip angle within the heart increased from 88 ± 9.1% with single-source to 103 ± 5.6% (P < 0.001) dual-source RF transmission. CNR increased for dual-source particularly at the apex (63.4 ± 24.2 vs. 36.5 ± 16.5, P < 0.001) but also at the base of the left ventricle (LV) (50.1 ± 14.8 vs. 39.3 ± 15.8, P < 0.001). Image quality of dual-source was higher both at rest (2.8 ± 0.5 vs. 2.6 ± 0.7, P < 0.001) and stress (2.5 ± 0.7 vs. 2.0 ± 1.0, P < 0.001). The number of segments with severe artifacts or nondiagnostic image quality at stress was lower with dual-source RF transmission (8% vs. 27%, P < 0.001). The diagnostic accuracy of DSMR in coronary territories using dual-source RF transmission was significantly higher (77% vs. 65%, P = 0.04). CONCLUSION: Patient adaptive local RF shimming using dual-source RF transmission provided significantly improved image quality and higher diagnostic accuracy of SSFP during DSMR at 3T compared to conventional RF transmission.

Second generation of cryoballoons can improve efficiency of cryoablation for atrial fibrillation.

BACKGROUND: We investigated whether the new second generation of cryoballoons can improve the efficiency and safety of cryoablation for atrial fibrillation (AF) during ablation and in terms of outcome. METHODS: Data of AF patients consecutively treated with a single 28-mm cryoballoon were analyzed. Patients were divided into two groups: the G1 group was treated with the first-generation cryoballoons (ArcticFront) and G2 with the second generation (ArcticFront Advance). Failure of cryoablation treatment was defined as detection of an episode of AF, atrial flutter, or atrial tachycardia lasting ≥ 30 seconds during 3-month follow-up. Left atrial diameter (LAD) was measured by transthoracic echocardiography before cryoablation. RESULTS: One hundred twenty-five patients (group G1/G2: 57/68) were enrolled. Mean total time of the whole procedure, cryomapping, and cryoablation was shorter with G2 than with G1 (P < 0.05). No complication occurred with G1 whereas with G2 the complication rate was 8.8%. During mean 12 ± 4 months follow-up, the overall success rate of cryoablation was 76.0% (95/125); it was higher with G2 (89.7% [61/68] vs 59.7% [34/57], P < 0.001). Patients in whom treatment failed had larger LAD (48 ± 8 mm vs 44 ± 6 mm, P = 0.002) than those in whom it succeeded. Type of cryoballoon (relative risk [RR] = 5.75 [2.16, 15.27], P < 0.0001) and LAD (RR = 0.90 [0.83, 0.97], P = 0.0043) were shown in multivariable analysis to be individually related to the difference in success rate. CONCLUSION: Ablation for AF with the new generation of cryoballoons is associated with higher success rate of pulmonary vein isolation and better outcome. However, more complications occurred during the early stage of application of the G2 cryoballoon.

German Heart Report 2013.

OBJECTIVES: The 25th German Heart Report provides a comprehensive analysis of morbidity and mortality in patients with selected heart diseases as well as services and care in cardiology and cardiac surgery in Germany during the period 2011-2012. It is the result of a multidisciplinary collaboration between the German Heart Foundation, the German Cardiac Society, the German Society for Thoracic and Cardiovascular Surgery, and the German Society of Pediatric Cardiology and is based on data from different sources. In addition, trends of the period from 1995 to 2012 are presented. RESULTS: The trends in morbidity due to cardiac diseases in 2010 and previous years continued in 2011. Compared with data from 1995 to 2010, one can observe: · a slight decrease in ischemic heart disease in every age group.. · a distinct increase in valve diseases, predominantly at age >75 years.. · an increase in arrhythmias from the age of 45 years on.. · an increase in cardiac failure, especially beyond the age of 75 years.. Compared with data from 2009, the mortality rates in 2011 differ somewhat; there is: · a decrease in heart failure and coronary heart disease.. · no change in arrhythmias.. · a distinct increase in valvular heart diseases.. · an additional, small decrease in congenital heart defects.. These data are in agreement with findings from other Western countries. Coronary heart disease, the most frequent cardiac disease, has continuously decreased in frequency and mortality since 2000. The underlying reasons are discussed. CONCLUSION: This report is an important resource for all parties of the healthcare system regarding heart disease conditions and their treatment in Germany.

Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial.

AIMS: Sympathetic stimulation induces left ventricular hypertrophy and is associated with increased cardiovascular risk. Catheter-based renal denervation (RDN) has been shown to reduce sympathetic outflow and blood pressure (BP). The present multi-centre study aimed to investigate the effect of RDN on anatomic and functional myocardial parameters, assessed by cardiac magnetic resonance (CMR), in patients with resistant hypertension. METHODS AND RESULTS: Cardiac magnetic resonance was performed in 72 patients (mean age 66 ± 10 years) with resistant hypertension (55 patients underwent RDN, 17 served as controls) at baseline and after 6 months. Clinical data and CMR results were analysed blindly. Renal denervation significantly reduced systolic and diastolic BP by 22/8 mm Hg and left ventricular mass index (LVMI) by 7.1% (46.3 ± 13.6 g/m(1.7) vs. 43.0 ± 12.6 g/m(1.7), P < 0.001) without changes in the control group (41.9 ± 10.8 g/m(1.7) vs. 42.0 ± 9.7 g/m(1.7), P = 0.653). Ejection fraction (LVEF) in patients with impaired LVEF at baseline (<50%) significantly increased after RDN (43% vs. 50%, P < 0.001). Left ventricular circumferential strain as a surrogate of diastolic function in the subgroup of patients with reduced strain at baseline increased by 21% only in the RDN group (-14.8 vs. -17.9; P = 0.001) and not in control patients (-15.5 vs. -16.4, P = 0.508). CONCLUSIONS: Catheter-based RDN significantly reduced BP and LVMI and improved EF and circumferential strain in patients with resistant hypertension, occurring partly BP independently.

Value of additional strain analysis with feature tracking in dobutamine stress cardiovascular magnetic resonance for detecting coronary artery disease.

BACKGROUND: Dobutamine stress cardiovascular magnetic resonance (DS-CMR) has been established for the detection of coronary artery disease (CAD). The novel technique feature tracking (FT) analyses left ventricular circumferential strain (Ecc) thus offering detailed information about myocardial deformation. The purpose of this study was to evaluate FT based Ecc for the detection of myocardial ischemia during DS-CMR. METHODS: A total of 25 patients (18 males; mean age 64 ± 10 years) with suspected or known CAD underwent a standardized high-dose DS-CMR protocol at 1.5 T. For FT analysis cine short axis (SAX) views (apical, medial, basal) at rest and during maximum dobutamine stress were used. None of the patients had wall motion abnormalities (WMAs) or impaired left ventricular function at rest or scar tissue. For analysis of Ecc the three SAX planes were divided into 16 segments (n = 400 segments). During stress 15 patients (34 segments) developed WMAs as assessed by visual analysis. All patients underwent x-ray coronary angiography for clinical reasons which served as the reference standard. Patients without WMAs during DS-CMR and exclusion of stenotic CAD were defined as normal (10 patients, 160 segments). In patients with significant CAD segments that were supplied by a vessel of >70% narrowing were defined as stenotic (n = 64). The remaining segments in patients with significant CAD were considered as remote (n = 176). RESULTS: At rest no differences in Ecc were observed between normal, stenotic and remote segments. High-dose dobutamine stress revealed highly significant differences between Ecc of normal and stenotic segments (p < 0.001), as well as between remote and stenotic segments (p < 0.001). The same observation took place for the absolute change of Ecc (p < 0.001 and p = 0.01). ROC analysis of Ecc during maximum DS-CMR differentiated normal from stenotic segments with a sensitivity of 75% and specificity of 67% using a cutoff -33.2% with an area under the curve of 0.78. Additional analysis of intermediate-dose dobutamine also showed a significant difference between normal and stenotic segments (p = 0.001). CONCLUSION: FT based analysis of Ecc during intermediate- and high-dose DS-CMR was feasible and differentiated between stenotic, remote and normal segments. Quantitative assessment of Ecc with FT may improve the diagnostic accuracy of DS-CMR for detection of ischemia.

Prolonged ablation on critical segments of pulmonary vein ostia in paroxysmal atrial fibrillation: a prospective randomized controlled study.

INTRODUCTION: Electrical reconnection of the pulmonary veins (PVs) plays a key role in the recurrence of atrial fibrillation (AF) after ablative treatment. This randomized controlled study tested the hypothesis that prolonged ablations, on areas that may be critical for left atrial (LA)-PV conduction, can significantly reduce the rate of acute PV reconnection and AF recurrence. METHODS: Patients with paroxysmal AF were randomly assigned to either a control or an add-on group.Ostial PV isolation (PVI) was performed by point-to-point RF ablation (irrigated tip, 30 Watts, 30 seconds).An ostial segment was assumed to be critical for LA-PV connection if any of the following reactions occurred during RF application: (1) sudden delay of LA-PV conduction, (2) change of activation sequence,and (3) PVI. In this case, RF application was prolonged from 30 seconds to 90 seconds in the add-on group only. RESULTS: A total of 131 patients (58 ± 11 years, 47 female) were assigned to a control (n = 64) and an add-on (n = 67) group. Ablation time was longer in the add-on (48 ± 16 minutes vs 37 ± 15 minutes, P = 0.03). Acute PV reconnection was observed in 20 of 64 controls and in eight of 66 add-on patients (31% vs 12%, P < 0.001). During a follow-up of 26 months, AF recurred in 33 of 64 controls and in 16 of 66 add-on patients (52% vs 24%, P = 0.001) after a single ablation procedure. CONCLUSIONS: Prolonged radiofrequency application on critical segments of LA-PV connection is a safe and effective ablative strategy that significantly reduces acute PV reconnection and AF recurrence rates after a single ablation procedure for paroxysmal AF.

Comparison of myocardial tagging and feature tracking in patients with severe aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Transcatheter aortic valve implantation (TAVI) has become an effective treatment for severe aortic stenosis (AS) in patients considered to be at high surgical risk. However, data relating to myocardial function and deformation in these patients are rare. Cardiovascular magnetic resonance (CMR) tagging has been established as non-invasive technique for the accurate measurement of myocardial motion. However, additional tagging datasets are necessary and the post-processing procedure is time-consuming. Recently, the novel technique of feature tracking (FT) was introduced, with which myocardial strain can be derived directly from balanced steady-state free precession (bSSFP) cine sequences. The study aim was to compare tagging with FT in patients with high-grade AS and who had been considered for TAVI. METHODS: Thirty patients with severe AS underwent cardiac magnetic resonance imaging at 1.5 T (Philips Achieva). A stack of serial short-axis slices was used to assess left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and LV mass and function. TomTec 2D Cardiac Performance Analysis software was used to derive myocardial deformation parameters from three short-axis cine views (basal, medial and apical levels) using bSSFP. All patients also underwent myocardial tagging on identical short-axis views, and data acquired from FT and tagging were compared. RESULTS: The mean left ventricular ejection fraction (LVEF), LVEDV and LVESV (57 ± 14%, 158 ± 58 ml, and 74 ± 48 ml, respectively) were all normal. All patients demonstrated concentric hypertrophy of the left ventricle with an increased basal septal thickness (16 ± 3 mm), LV mass (126 ± 40 g) and indexed LV mass (68 ± 23 g/m2, papillary muscles excluded). Bland-Altman analysis revealed a reasonable agreement between basal and medial circumferential strain (cc), and a good correlation was observed between tagging and FT for the derived basal and medial cc (Pearson's correlation coefficient 0.83 for basal, 0.74 for medial). Basal rotation was impaired compared to previous studies in patients with AS, but medial and apical rotations were comparable. The apical peak diastolic rotation velocity was faster compared to earlier analyses. Rotation, peak systolic and end-diastolic rotation velocity did not demonstrate any correlation or acceptable agreement between FT and tagging. The inter-observer agreement as assessed by the intra- class correlation coefficient for FT showed good results for the cc (basal 0.94, medial 0.83, apical 0.75). CONCLUSION: To the present authors' knowledge, this is the first study to assess myocardial motion using tagging and FT in patients with AS prior to TAVI. A reasonable agreement was found for the basal and medial cc between both techniques. Estimated cc-values using FT were systematically higher than those with tagging, but this might have been due to the different techniques employed. Although FT is a promising method to assess cc, further studies including the evaluation of standard values--and investigations with different diseases are necessary.

Electromagnetic interference of avalanche transceivers with cardiac pacemakers and implantable cardioverter defibrillators.

BACKGROUND: Avalanche transceivers are essentials tools in locating persons who were buried by an avalanche. In the past few years, avalanche transceivers have become widely available and affordable, but it is largely unknown whether they are a source of electromagnetic interference for implanted cardiac devices. We aimed to determine the potential interaction between avalanche transceivers and pacemakers or implantable cardioverter defibrillators (ICDs). METHODS: One hundred and one patients, 41 with pacemakers and 60 with ICDs, were enrolled (mean age 66 ± 15 years). Four avalanche transceivers (Pieps DSP [Pieps GmbH, Lebring, Austria], Ortovox x1, Ortovox m2, and Ortovox f1 [Otovox Sportartikel GmbH, Taufkirchen, Germany]) were evaluated in transmit as well as in receive mode. Surface electrocardiograms, intracardiac electrograms, and marker channels were continuously recorded and observed by an experienced physician. Electromagnetic interference events were categorized as direct interference with the function of the implanted device itself or as interference with the telemetric communication without compromising device function. RESULTS: Among all patients, there was no interference with the intrinsic function of their pacemakers or ICDs. A total of 120 episodes of telemetry interference occurred in 48% of the patients. Of those episodes, 112 of 404 (28%) were observed in transmit and eight of 404 (2%) in receive mode (P < 0.0001). The digital avalanche transceiver (Pieps DSP) was associated with significantly less telemetry interference (20/202; 10%) than the analog transceiver (Ortovox f1) (39/202; 19%) (P = 0.0108). CONCLUSIONS: Avalanche transceivers are safe for patients with pacemakers and ICDs. Despite the observed telemetry interferences, the intrinsic function of the implanted devices was never compromised.

In Vivo Fluorine Imaging Using 1.5 Tesla MRI for Depiction of Experimental Myocarditis in a Rodent Animal Model.

The usefulness of perfluorocarbon nanoemulsions for the imaging of experimental myocarditis has been demonstrated in a high-field 9.4 Tesla MRI scanner. Our proof-of-concept study investigated the imaging capacity of PFC-based 19F/1H MRI in an animal myocarditis model using a clinical field strength of 1.5 Tesla. To induce experimental myocarditis, five male rats (weight ~300 g, age ~50 days) were treated with one application per week of doxorubicin (2 mg/kg BW) over a period of six weeks. Three control animals received the identical volume of sodium chloride 0.9% instead. Following week six, all animals received a single 4 ml injection of an 20% oil-in-water perfluorooctylbromide nanoemulsion 24 hours prior to in vivo1H/19F imaging on a 1.5 Tesla MRI. After euthanasia, cardiac histology and immunohistochemistry using CD68/ED1 macrophage antibodies were performed, measuring the inflamed myocardium in µm2 for further statistical analysis to compare the extent of the inflammation with the 19F-MRI signal intensity. All animals treated with doxorubicin showed a specific signal in the myocardium, while no myocardial signal could be detected in the control group. Additionally, the doxorubicin group showed a significantly higher SNR for 19F and a stronger CD68/ED1 immunhistoreactivity compared to the control group. This proof-of-concept study demonstrates that perfluorocarbon nanoemulsions could be detected in an in vivo experimental myocarditis model at a currently clinically relevant field strength.

Virtual cardiovascular magnetic resonance training proves feasible and effective: survey data from international participants of the CMR Academy Berlin, Germany.

Aims: This study aims to evaluate the success of the cardiovascular magnetic resonance (CMR) imaging Academy Berlin's transition from in-person to online CMR imaging training during the global pandemic 2020 and to gather recommendations for future courses. Methods and results: We conducted an online survey targeting CMR course participants from both the pre-pandemic, in-person era and the pandemic, online era of the CMR Academy Berlin. The survey primarily used Likert-type questions to assess participants' experiences and preferences.A total of 61 out of 158 invited participants (38.61%) completed the survey, with 31 (50.82%) being in-person alumni and 30 (49.18%) being online alumni. Both in-person [83.87% (26/31)] and online [83.33% (25/30)] participants rated the course as either 'very good' or 'excellent', and both groups found the course either 'extremely helpful' or 'very helpful'. However, a higher percentage of in-person participants [96.77% (30/31)] felt comfortable asking questions compared to online participants [83.33% (25/30); P = 0.025]. The majority in both groups preferred a written exam [total: 75.41% (46/61); in-person alumni: 77.42% (24/31); online alumni 73.33% (22/30)]. In terms of course format preferences, in-person courses were preferred by both in-person alumni [38.71% (12/31)] and online alumni [60% (18/30)], almost as much as a hybrid format combining in-person and online elements [in-person alumni: 41.94% (13/31), online alumni: 30% (9/30)]. Conclusion: The transition from in-person to online CMR training at the CMR Academy Berlin was successful in maintaining overall satisfaction. However, there is room for improvement in terms of increased interaction, particularly for online participants. Future CMR- and potentially also cardiac computer tomography-courses should consider adopting a hybrid format to accommodate participants' preferences and enhance their learning experience, especially to gain level II competency, whereas level I virtual only might be sufficient.

The COVID-19 pandemic has greatly changed the landscape of medical education, necessitating the shift from traditional in-person learning to online platforms. This study evaluated how well an online training programme for cardiovascular magnetic resonance imaging (CMR) was received by doctors who attended the CMR Academy in Berlin, Germany. We asked both in-person and online course participants about their experiences and preferences for future courses. A total of 61 out of 158 participants (38.61%) responded to our survey. Both in-person and online attendees rated the course as either 'very good' or 'excellent'. However, more in-person attendees felt comfortable asking questions during the course compared to online attendees. In terms of future courses, most of the participants preferred a blend of in-person and online learning, known as a hybrid format. They felt that online learning had some benefits, such as increased access, especially during a pandemic. However, they missed the interaction and engagement that in-person learning provides. They also preferred written exams to be conducted online. This study emphasizes the need for future CMR training to be more flexible and include both online and in-person elements. This would not only accommodate the participants' preferences but also enhance their learning experience. It also stresses the importance of interaction during the learning process, which needs to be improved in online platforms. The findings can potentially inform the development of educational frameworks in other areas of medical imaging, like cardiac computer tomography (CT).

Visualization of chronic myocardial infarction using the intravascular contrast agent MS-325 (gadofosveset) in patients.

AIMS: The aim of this study was to evaluate the potential of visualizing chronic myocardial infarction in patients using the intravascular CA MS-325 (gadofosveset, EPIX Pharmaceuticals, Mass, USA). METHODS: Nine patients were enrolled in a clinical phase II multicenter trial for MRCA and perfusion imaging using MS-325. They had objective evidence of chronic myocardial infarction as visualized by previously performed late gadolinium (Gd) enhancement imaging (LGE) with a conventional extracellular Gd-DTPA CA (Magnevist, Bayer Healthcare, Germany, 0.2 mmol/kg/body weight) serving as reference standard. A prepulse-optimized LGE study was performed immediately and at several time points after injection of MS-325 (0.05 mmol/kg/body weight). The number and localization of segments demonstrating LGE with MS-325 as well as signal intensities were compared with the reference standard (Gd-DTPA). RESULTS: Using MS-325, LGE could be detected at every time point in all 9 patients. The accuracy of LGE with MS-325 as compared to LGE with Gd-DTPA was highest 54 ± 4 minutes after contrast injection, resulting in a sensitivity of 84% with a specificity of 98%. CONCLUSION: The intravascular CA MS-325 has the potential to visualize chronic myocardial infarction. However, in comparison with Gd-DTPA, the transmural extent and the number of segments are smaller.

CD40/CD40L interaction induces E-selectin dependent leukocyte adhesion to human endothelial cells and inhibits endothelial cell migration.

BACKGROUND: CD40 is a receptor expressed on a wide range of cells such as leukocytes and endothelial cells (EC). As a member of the tumor necrosis factor (TNF) superfamily the activation of CD40 by CD40-ligand (CD40L) plays a crucial role for the development and progression of a variety of inflammatory processes including atherosclerosis. The aim of the present study was to investigate the effect of CD40/CD40L interaction on leukocyte adhesion to the endothelium and on endothelial cell migration. METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVEC) were stimulated with either stable transfectants of mouse myeloma cells expressing the CD40L or wild type cells (4 h). Subsequently adhesion of leukocytes expressing Sialyl Lewis X, the counterpart for E-selectin (HL60 cells), was measured under shear stress (2-2.6 dyne/cm(2)) using a flow chamber adhesion assay. Stimulation of CD40 led to a significant increase of E-selectin dependent adhesion of leukocytes to the endothelium. Incubation of cells with either the CD40L blocking antibody TRAP-1 or the E-selectin blocking antibody BBA2 during CD40 stimulation completely abolished adhesion of leukocytes to HUVEC. Similar results were found in human cardiac microvasculature endothelial cells (HCMEC). In contrast stimulation of CD40 had no effect on adhesion of L-selectin expressing NALM6-L cells. Furthermore, CD40/CD40L interaction abrogated VEGF-induced migration of HUVEC compared to non-stimulated controls. In comparison experiments, stimulation of endothelial cells with VEGF led to a significant phosphorylation of ERK1/2, Akt, and eNOS. Stimulation of endothelial CD40 had no effect on VEGF-induced phosphorylation of ERK1/2. However, VEGF-induced activation of Akt and eNOS was reduced to baseline levels when endothelial CD40 was stimulated. CONCLUSION: CD40/CD40L interaction induces E-selectin dependent adhesion of leukocytes to human endothelial cells and reduces endothelial cell migration by inhibiting the Akt/eNOS signaling pathway.

Cardiovascular magnetic resonance imaging for accurate sizing of the left atrium: predictability of pulmonary vein isolation success in patients with atrial fibrillation.

PURPOSE: To prospectively determine the most reproducible approach for left-atrial size assessment using cardiovascular magnetic resonance (CMR) imaging in patients with atrial fibrillation and its value for prediction of pulmonary vein isolation (PVI) treatment success. MATERIALS AND METHODS: Eighty patients underwent CMR imaging prior to PVI; the CMR examination included standard cine sequences, a multislice cine sequence in 4-chamber orientation with full left-atrial coverage, and a contrast-enhanced MR angiography of the left atrium. Left-atrial size was determined as: diameter, area, volume segmented from angiography, and diastolic/systolic volumes from cine imaging (Simpson's rule). All measurements were carried out by two independent observers and repeated by one observer to assess inter- and intrareader variability. Treatment success was defined as persisting sinus rhythm after PVI (follow-up period 12.6 ± 6.6 months). RESULTS: All left-atrial measurements showed substantial intrareader agreement. Interreader agreement was substantial for diastolic/systolic left-atrial volumes only. Calculated bias was found to be minimal (0.1%-4.9%). Predictability of PVI treatment success was best using cine volumetric measurements (cutoff value for diastolic volume, 112 mL) yielding a sensitivity and specificity of 80% and 70%, respectively. CONCLUSION: Left-atrial volumetry based on cine imaging represented the most reproducible approach to determine left-atrial size. PVI success was predicted best using cine volumetry.

Fully automatic geometry planning for cardiac MR imaging and reproducibility of functional cardiac parameters.

PURPOSE: To establish operator-independent, fully automated planning of standard cardiac geometries and to determine the impact on interstudy reproducibility of cardiac functional parameters. MATERIALS AND METHODS: Cardiac MR imaging was done in 50 patients referred for left-ventricular function assessment. In all patients, first standard manual planning was performed followed by automatic planning (AUTO1) and repeat automatic planning (AUTO2) after repositioning the patient to investigate interstudy reproducibility. Cardiac functional parameters were assessed and cine scans were visually graded on a 4-point scale from nondiagnostic to excellent. RESULTS: Overall success rate of AUTO was 94% with good to excellent geometry planning in >94% of cine standard views. Comparing manual versus fully automated planning, a high agreement of cardiac functional parameters (Lin's concordance correlation coefficient, 0.91 to 0.99) with minimal percent bias (0.24 to 3.84%) was found. In addition, a high interstudy reproducibility of automatic planning was demonstrated (Lin's concordance correlation coefficient, 0.89 to 0.99; percent bias, 0.38 to 5.04%; precision, 3.46 to 9.09%). CONCLUSION: Fully automated planning of cardiac geometries could reliably be performed in patients showing a variety of cardiovascular pathologies. Standard cardiac geometries were precisely replicated and functional parameters were highly accurate.

The role of dobutamine stress cardiovascular magnetic resonance in the clinical management of patients with suspected and known coronary artery disease.

BACKGROUND: Recent studies have demonstrated the consistently high diagnostic and prognostic value of dobutamine stress cardiovascular magnetic resonance (DCMR). The value of DCMR for clinical decision making still needs to be defined. Hence, the purpose of this study was to assess the utility of DCMR regarding clinical management of patients with suspected and known coronary artery disease (CAD) in a routine setting. METHODS AND RESULTS: We prospectively performed a standard DCMR examination in 1532 consecutive patients with suspected and known CAD. Patients were stratified according to the results of DCMR: DCMR-positive patients were recommended to undergo invasive coronary angiography and DCMR-negative patients received optimal medical treatment. Of 609 (40%) DCMR-positive patients coronary angiography was performed in 478 (78%) within 90 days. In 409 of these patients significant coronary stenoses ≥ 50% were present (positive predictive value 86%). Of 923 (60%) DCMR-negative patients 833 (90%) received optimal medical therapy. During a mean follow-up period of 2.1 ± 0.8 years (median: 2.1 years, interquartile range 1.5 to 2.7 years) 8 DCMR-negative patients (0.96%) sustained a cardiac event.In 131 DCMR-positive patients who did not undergo invasive angiography, 20 patients (15%) suffered cardiac events. In 90 DCMR-negative patients (10%) invasive angiography was performed within 2 years (range 0.01 to 2.0 years) with 56 patients having coronary stenoses ≥ 50%. CONCLUSION: In a routine setting DCMR proved a useful arbiter for clinical decision making and exhibited high utility for stratification and clinical management of patients with suspected and known CAD.

Use of 2D sensitivity encoding for slow-infusion contrast-enhanced isotropic 3-T whole-heart coronary MR angiography.

OBJECTIVE: The purpose of this study was to improve the blood-pool signal-to-noise ratio (SNR) and blood-myocardium contrast-to-noise ratio (CNR) of slow-infusion 3-T whole-heart coronary MR angiography (MRA). SUBJECTS AND METHODS: In 2D sensitivity encoding (SENSE), the number of acquired k-space lines is reduced, allowing less radiofrequency excitation per cardiac cycle and a longer TR. The former can be exploited for signal enhancement with a higher radiofrequency excitation angle, and the latter leads to noise reduction due to lower data-sampling bandwidth. Both effects contribute to SNR gain in coronary MRA when spatial and temporal resolution and acquisition time remain identical. Numeric simulation was performed to select the optimal 2D SENSE pulse sequence parameters and predict the SNR gain. Eleven patients underwent conventional unenhanced and the proposed 2D SENSE contrast-enhanced coronary MRA acquisition. Blood-pool SNR, blood-myocardium CNR, visible vessel length, vessel sharpness, and number of side branches were evaluated. RESULTS: Consistent with the numeric simulation, using 2D SENSE in contrast-enhanced coronary MRA resulted in significant improvement in aortic blood-pool SNR (unenhanced vs contrast-enhanced, 37.5 ± 14.7 vs 121.3 ± 44.0; p < 0.05) and CNR (14.4 ± 6.9 vs 101.5 ± 40.8; p < 0.05) in the patient sample. A longer length of left anterior descending coronary artery was visualized, but vessel sharpness, coronary artery coverage, and image quality score were not improved with the proposed approach. CONCLUSION: In combination with contrast administration, 2D SENSE was found effective in improving SNR and CNR in 3-T whole-heart coronary MRA. Further investigation of cardiac motion compensation is necessary to exploit the SNR and CNR advantages and to achieve submillimeter spatial resolution.

Frequency analysis of atrial fibrillation surface and intracardiac electrograms during pulmonary vein isolation.

AIMS: Frequency analysis of atrial electrograms from patients diagnosed with persistent atrial fibrillation (AF) appears to be crucial in its clinical diagnosis. This work explores the fibrillatory frequency properties of both surface and intracardiac electrograms before and after pulmonary vein isolation (PVI) using three time-frequency techniques. METHODS AND RESULTS: Surface electrocardiograms (ECGs) of 21 patients diagnosed with persistent AF undergoing PVI were recorded. Three methods, Fourier, ensemble average, and wavelet analysis, were used to identify the dominant frequency (DF) in surface ECGs. Dominant frequency was also computed in electrograms recorded within the coronary sinus (CS). Dominant frequency measured within the CS was best estimated in surface lead V1 using both Fourier (relative error: 10.94 ± 10.37%, correlation: 0.58) and wavelet analysis (relative error: 10.97 ± 11.08%, correlation: 0.53). Ensemble average gave highest relative error (21.29 ± 18.07%) and lowest correlation (0.10). Dominant frequency decreased after right PVI. This decrease was significant (P< 0.05) in most of the patients (13, 14, and 7 out of 14 when Fourier, wavelets, and ensemble average was used; 14 in CS). Further isolation of the left pulmonary veins (PVs) yielded a significant (P< 0.05) decrease in only a few of them (3, 4, and 2 out of 14 when Fourier, wavelets, and ensemble average was used; 4 in CS). CONCLUSION: Wavelet and Fourier analysis are good tools for estimating the atrial fibrillatory rate from surface ECG. A drop was observed in the DF value after isolation of the right PV. However, after left PVI this decrease was smaller.