Timm Dickfeld

Magnetic Resonance Assessment of the Substrate for Inducible Ventricular Tachycardia in Nonischemic Cardiomyopathy

Background— Patients with left ventricular dysfunction have an elevated risk of sudden cardiac death. However, the substrate for ventricular arrhythmia in patients with nonischemic cardiomyopathy remains poorly understood. We hypothesized that the distribution of scar identified by MRI is predictive of inducible ventricular tachycardia. Methods and Results— Short-axis cine steady-state free-precession and postcontrast inversion-recovery gradient-echo MRI sequences were obtained before electrophysiological study in 26 patients with nonischemic cardiomyopathy. Left ventricular ejection fraction was measured from end-diastolic and end-systolic cine images. The transmural extent of scar as a percentage of wall thickness (percent scar transmurality) in each of 12 radial sectors per slice was calculated in all myocardial slices. The percentages of sectors with 1% to 25%, 26% to 50%, 51% to 75%, and 76% to 100% scar transmurality were determined for each patient. Predominance of scar distribution involving 26% to 75% of wall thickness was significantly predictive of inducible ventricular tachycardia and remained independently predictive in the multivariable model after adjustment for left ventricular ejection fraction (odds ratio, 9.125; P=0.020). Conclusions— MR assessment of scar distribution can identify the substrate for inducible ventricular tachycardia and may identify high-risk patients with nonischemic cardiomyopathy currently missed by ejection fraction criteria.

Clinical utility and safety of a protocol for noncardiac and cardiac magnetic resonance imaging of patients with permanent pacemakers and implantable-cardioverter defibrillators at 1.5 tesla.

Background— Magnetic resonance imaging (MRI) is an important diagnostic modality currently unavailable for millions of patients because of the presence of implantable cardiac devices. We sought to evaluate the diagnostic utility and safety of noncardiac and cardiac MRI at 1.5T using a protocol that incorporates device selection and programming and limits the estimated specific absorption rate of MRI sequences. Methods and Results— Patients with no imaging alternative and with devices shown to be MRI safe by in vitro phantom and in vivo animal testing were enrolled. Of 55 patients who underwent 68 MRI studies, 31 had a pacemaker, and 24 had an implantable defibrillator. Pacing mode was changed to “asynchronous” for pacemaker-dependent patients and to “demand” for others. Magnet response and tachyarrhythmia functions were disabled. Blood pressure, ECG, oximetry, and symptoms were monitored. Efforts were made to limit the system-estimated whole-body average specific absorption rate to 2.0 W/kg (successful in >99% of sequences) while maintaining the diagnostic capability of MRI. No episodes of inappropriate inhibition or activation of pacing were observed. There were no significant differences between baseline and immediate or long-term (median 99 days after MRI) sensing amplitudes, lead impedances, or pacing thresholds. Diagnostic questions were answered in 100% of nonthoracic and 93% of thoracic studies. Clinical findings included diagnosis of vascular abnormalities (9 patients), diagnosis or staging of malignancy (9 patients), and assessment of cardiac viability (13 patients). Conclusions— Given appropriate precautions, noncardiac and cardiac MRI can potentially be safely performed in patients with selected implantable pacemaker and defibrillator systems.

Activated Platelets Induce Monocyte Chemotactic Protein-1 Secretion and Surface Expression of Intercellular Adhesion Molecule-1 on Endothelial Cells

BACKGROUNDnPlatelet/endothelium interaction plays an important role in the pathophysiology of inflammation and atherosclerosis. The role of platelets for monocyte chemotactic protein-1 (MCP-1) secretion and surface expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells has been assessed.nnnMETHODS AND RESULTSnMonolayers of human umbilical vein endothelial cells were incubated with nonstimulated or ADP-activated platelets for 6 hours, and secretion of MCP-1 and surface expression of ICAM-1 were determined by ELISA and flow cytometry, respectively. In the presence of ADP-activated platelets, both MCP-1 secretion and ICAM-1 surface expression were significantly increased compared with nonstimulated platelets (P<0.02). Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) determined by electrophoretic mobility shift assay and kappaB-dependent transcriptional activity was enhanced in the presence of activated platelets. In addition, ADP-activated platelets induced MCP-1 and ICAM-1 promoter-dependent transcription. Liposomal transfection of a double-stranded kappaB phosphorothioate oligonucleotide, but not of the mutated form, inhibited MCP-1 secretion and surface expression of ICAM-1 on activated endothelium (P<0.05).nnnCONCLUSIONSnThe present study indicates that activated platelets modulate chemotactic (MCP-1) and adhesive (ICAM-1) properties of endothelial cells via an NF-kappaB-dependent mechanism. Platelet-induced activation of the NF-kappaB system might contribute to early inflammatory events in atherogenesis.

Vitronectin Receptor (αvβ3) Mediates Platelet Adhesion to the Luminal Aspect of Endothelial Cells Implications for Reperfusion in Acute Myocardial Infarction

Background Platelet interaction with endothelium plays an important role in the pathophysiology of coronary microcirculation. We assessed the role of the vitronectin receptor (integrin αvβ3) in platelet/endothelium adhesion. Methods and Results We investigated the effect on platelet/endothelium adhesion of plasma obtained from patients with acute myocardial infarction during reperfusion (before and 8, 24, 48, and 72 hours and 5 to 7 days after direct angioplasty) and with pretreatment with α-thrombin (2 U/mL) and recombinant human interleukin-1β. Platelet/endothelium adhesion was significantly enhanced by ≈20% after pretreatment of endothelium with patient plasma for 4 hours (P<.05) compared with endothelium treated with pooled control plasma. Plasma-induced platelet/endothelium adhesion was, in part, RGD peptide dependent. Pretreatment of endothelial cells with α-thrombin or recombinant human interleukin-1β enhanced platelet/endothelium adhesion and surface expression of αvβ3 on the luminal aspect of end...

EHRA/HRS/APHRS expert consensus on ventricular arrhythmias.

Christian Torp Pedersen (EHRA Chairperson, Denmark), G. Neal Kay (HRS Chairperson, USA), Jonathan Kalman (APHRS Chairperson, Australia), Martin Borggrefe (Germany), Paolo Della-Bella (Italy), Timm Dickfeld (USA), Paul Dorian (Canada), Heikki Huikuri (Finland), Youg-Hoon Kim (Korea), Bradley Knight (USA), Francis Marchlinski (USA), David Ross (Australia), Frédéric Sacher (France), John Sapp (Canada), Kalyanam Shivkumar (USA), Kyoko Soejima (Japan), Hiroshi Tada (Japan), Mark E. Alexander (USA), John K. Triedman (USA), Takumi Yamada (USA), and Paulus Kirchhof (Germany)

Incidence and Predictors of Pulmonary Vein Stenosis Following Catheter Ablation of Atrial Fibrillation Using the Anatomic Pulmonary Vein Ablation Approach: Results from Paired Magnetic Resonance Imaging

Introduction: There are currently no studies systematically evaluating pulmonary vein (PV) stenosis following catheter ablation of atrial fibrillation (AF) using the anatomic PV ablation approach.

Platelet function in septic multiple organ dysfunction syndrome

AbstractObjective: Altered platelet function plays a role in the pathophysiology of multiple organ failure in sepsis. The purpose of the present study was to evaluate various aspects of platelet adhesive function in septic patients and its putative relevance for prognosis.nn Design: Prospective clinical study.nn Setting: Intensive Care Unit of the University Hospital.nn Patients and methods: A total of 41 patients admitted to the medical Intensive Care Unit were studied. On the day of admission, patients were evaluated by intensive care scoring systems (Elebute, APACHE II) to assess the severity of sepsis and multiple organ dysfunction syndrome (MODS), and platelet function tests were performed. All patients were observed for 28 days to assess their clinical outcomes. Eleven patients revealed septicemia without MODS (Elebute ≥12, APACHE II <20) and 20 septic patients suffered from MODS (Elebute ≥12, APACHE II ≥20). Ten non-septic patients without MODS served as a control group (Elebute <12, APACHE II <20). Flow cytometric determination of the activated fibrinogen (fg) receptor GPIIb-IIIa and as well as thrombospondin (TSP) on platelets and platelet-neutrophil adhesion (CD41 immunofluorescence) ex vivo was performed using monoclonal antibodies. The effect of plasma obtained from patients on normal platelet aggregation in vitro, and adhesion to cultured endothelial cells was evaluated.nn Results: The surface expression of TSP on platelets was increased in septic patients with MODS compared to controls (p<0.03). Platelet-neutrophil adhesion was not significantly altered in septicemia (p<0.09) but decreased significantly in the presence of MODS (p<0.05) when compared to controls. Logistic regression analysis showed that platelet-neutrophil adhesion was an independent predictor for poor clinical outcome (p<0.01). Plasma from septic patients sensitized normal platelets to hyperaggregate and to adhere to cultured endothelium (p<0.01).nn Conclusion: In septic patients platelets become activated and are hyperadhesive to other vascular cells including neutrophils and endothelium. This may induce sequestration of platelets and microcirculatory arrest, thus the development of MODS.

Feasibility of Real-Time Magnetic Resonance Imaging for Catheter Guidance in Electrophysiology Studies

Background— Compared with fluoroscopy, the current imaging standard of care for guidance of electrophysiology procedures, magnetic resonance imaging (MRI) provides improved soft-tissue resolution and eliminates radiation exposure. However, because of inherent magnetic forces and electromagnetic interference, the MRI environment poses challenges for electrophysiology procedures. In this study, we sought to test the feasibility of performing electrophysiology studies with real-time MRI guidance. Methods and Results— An MRI-compatible electrophysiology system was developed. Catheters were targeted to the right atrium, His bundle, and right ventricle of 10 mongrel dogs (23 to 32 kg) via a 1.5-T MRI system using rapidly acquired fast gradient-echo images (≈5 frames per second). Catheters were successfully positioned at the right atrial, His bundle, and right ventricular target sites of all animals. Comprehensive electrophysiology studies with recording of intracardiac electrograms and atrial and ventricular pacing were performed. Postprocedural pathological evaluation revealed no evidence of thermal injury to the myocardium. After proof of safety in animal studies, limited real-time MRI-guided catheter mapping studies were performed in 2 patients. Adequate target catheter localization was confirmed via recording of intracardiac electrograms in both patients. Conclusions— To the best of our knowledge, this is the first study to report the feasibility of real-time MRI-guided electrophysiology procedures. This technique may eliminate patient and staff radiation exposure and improve real-time soft tissue resolution for procedural guidance.

Radiation Exposure During Catheter Ablation of Atrial Fibrillation

Background—The purpose of this study was to determine the radiation exposure during catheter ablation of atrial fibrillation (AF) using the pulmonary vein (PV) approach. Methods and Results—The study included 15 patients with AF and 5 patients each with atrial flutter and atrioventricular nodal reentrant tachycardia (AVNRT) who underwent fluoroscopically guided procedures on a biplane x-ray system operated at a low-frame pulsed fluoroscopy (7.5 frames per second). Radiation exposure was measured directly with 50 to 60 thermoluminescent dosimeters (TLDs). Peak skin doses (PSDs), effective radiation doses, and risk of fatal malignancies were all computed. Mean fluoroscopy durations for AF procedures were 67.8±21 minutes in the right anterior oblique (RAO) and 61.9±16.6 minutes in the left anterior oblique (LAO) projection, significantly different from that required for atrial flutter and AVNRT. The mean PSDs measured with the TLDs were 1.0±0.5 Gy in the RAO and 1.5±0.4 Gy in the LAO projection. The lifetime risk of excess fatal malignancies normalized to 60 minutes of fluoroscopy was 0.07% for women and 0.1% for men. Conclusions—The relatively small amounts of the patient’s radiation exposure in this study, despite the prolonged fluoroscopy durations, can be attributed to the use of very-low-frame pulsed fluoroscopy, the avoidance of magnification, and optimal adjustments of the fluoroscopy exposure rates. The resulting lifetime risk of fatal malignancy is within the range previously reported for standard supraventricular arrhythmias.

Anatomic Stereotactic Catheter Ablation on Three-Dimensional Magnetic Resonance Images in Real Time

Background—Targets for radiofrequency (RF) ablation of atrial fibrillation, atrial flutter, and nonidiopathic ventricular tachycardia are increasingly being selected on the basis of anatomic considerations. Because fluoroscopy provides only limited information about the relationship between catheter positions and cardiac structures and is associated with radiation risk, other approaches to mapping may be beneficial. Methods and Results—An electromagnetic catheter positioning system was superimposed on 3D MR images using fiducial markers. This allowed the dynamic display of the catheter position on the true anatomy of previously acquired MR images in real time. In vitro accuracy and precision during catheter navigation were assessed in a phantom model and were 1.11±0.06 and 0.30±0.07 mm (mean±SEM), respectively. Left and right heart catheterization was performed in 7 swine without the use of fluoroscopy, yielding an in vivo accuracy and precision of 2.74±0.52 and 1.97±0.44 mm, respectively. To assess the reproducibility of RF ablation, RF lesions were created repeatedly at the identical anatomic site in the right atrium (n=8 swine). Average distance of the repeated right atrial ablations was 3.92±0.5 mm. Straight 3-point lines were created in the right and left ventricles to determine the ability to facilitate complex ablation procedures (n=6 swine). The ventricular lesions deviated 1.70±0.24 mm from a straight line, and the point distance differed by 2.25±0.63 mm from the pathological specimen. Conclusions—Real-time display of the catheter position on 3D MRI allows accurate and precise RF ablation guided by the true anatomy. This may facilitate anatomically based ablation procedures in, for instance, atrial fibrillation or nonidiopathic ventricular tachycardia and decrease radiation times.