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1.  Measurement of Left Atrial Pressure is a Good Predictor of Freedom From Atrial Fibrillation 
It is suggested that an elevated left atrial pressure (LAP) promotes ectopic beats emanating in the pulmonary veins (PVs) and that LAP might be a marker for structural remodeling. This study aimed to identify if the quantification of LAP correlates with structural changes of the LA and may therefore be associated with outcomes following pulmonary vein isolation (PVI).
We analysed data from 120 patients, referred to PVI due to drug-refractory atrial fibrillation (AF) (age 63±8; 57% men). The maximum (mLAP) and mean LAP (meLAP) were measured after transseptal puncture.
Results and Conclusions
Within a mean follow-up of 303±95 days, 60% of the patients maintained in sinus rhythm after the initial procedure and 78% after repeated PVI. Performing univariate Cox-regression analysis, type of AF, LA-volume (LAV), mLAP and the meLAP were significant predictors of recurrence after PVI (p=0.03; p=0.001; p=0.01). In multivariate analysis mLAP>18mmHg, LAV>100 ml and the presence of persistent AF were significant predictors (p=0.001; p=0.019; p=0.017). The mLAP >18 mmHg was associated with a hazard ratio of 3.8. Analyzing receiver-operator characteristics, the area under the curve for mLAP was 0.75 (p<0.01). mLAP >18 mmHg predicts recurrence with a sensitivity of 77 % and specificity of 60 %. There was a linear correlation between the LAV from MDCT and mLAP (p = 0.01, R2 = 0.61). The mLAP measured invasively displays a significant predictor for AF recurrence after PVI. There is a good correlation between LAP and LAV and both factors may be useful to quantify LA remodeling.
PMCID: PMC4100084  PMID: 25057219
atrial fibrillation; pulmonary vein ablation; predictors; left atrial pressure; remodeling; left atrial volume
2.  Accelerometer and Gyroscope Based Gait Analysis Using Spectral Analysis of Patients with Osteoarthritis of the Knee 
Journal of Physical Therapy Science  2014;26(7):997-1002.
[Purpose] A wide variety of accelerometer tools are used to estimate human movement, but there are no adequate data relating to gait symmetry parameters in the context of knee osteoarthritis. This study’s purpose was to evaluate a 3D-kinematic system using body-mounted sensors (gyroscopes and accelerometers) on the trunk and limbs. This is the first study to use spectral analysis for data post processing. [Subjects] Twelve patients with unilateral knee osteoarthritis (OA) (10 male) and seven age-matched controls (6 male) were studied. [Methods] Measurements with 3-D accelerometers and gyroscopes were compared to video analysis with marker positions tracked by a six-camera optoelectronic system (VICON 460, Oxford Metrics). Data were recorded using the 3D-kinematic system. [Results] The results of both gait analysis systems were significantly correlated. Five parameters were significantly different between the knee OA and control groups. To overcome time spent in expensive post-processing routines, spectral analysis was performed for fast differentiation between normal gait and pathological gait signals using the 3D-kinematic system. [Conclusions] The 3D-kinematic system is objective, inexpensive, accurate and portable, and allows long-term recordings in clinical, sport as well as ergonomic or functional capacity evaluation (FCE) settings. For fast post-processing, spectral analysis of the recorded data is recommended.
PMCID: PMC4135223  PMID: 25140082
Gait; Accelerometer; Gyroscope
3.  Comparison of end-diastolic versus end-systolic cardiac-computed tomography reconstruction interval in patient’s prior to pulmonary vein isolation 
SpringerPlus  2014;3:218.
Aim of the study was to investigate diagnostic accuracy of cardiac computed tomography angiography (CCTA) between left ventricular end-systolic (LVES) and left ventricular end-diastolic (LVED) cardiac phase for thrombus detection in patient’s prior to pulmonary vein isolation (PVI).
Materials and methods
182 consecutive Patients with drug refractory AF scheduled for PVI (62.6% male, mean age 64.1 ± 10.2 years) underwent routine pre-procedural evaluation including transesophageal echocardiography (TEE) and CCTA for evaluation of left atrial (LA)/left atrial appendage (LAA) anatomy and thrombus formation. Qualitative and quantitative analysis (using aorta ascendens (AA)/LAA ratio) was performed. Measurements of the LA/LAA in LVES and LVED cardiac phase were obtained.
End-systolic volumes (LA/LAA) measured in 30 patients without filling defects as control group and all 14 with filling defects of 182 patients were significantly larger (p < 0.01) than in end-diastolic phase. Qualitative analysis was inferior to quantitative analysis using LA/LAA ratio (<0.5; accuracy: 100%, 88%,100%, 99% vs 100%). 5 out of 182 patients (2.7%) showed thrombus formation of the LAA in CCTA confirmed by TEE and quantitative analysis. Intra/-interobserver variability was lower in end-systolic vs end-diastolic reconstruction interval.
For evaluating CCTA datasets in patients prior PVI, the LVES reconstruction interval is recommended due to significantly larger LA/LAA volumes and lower intra/- interobserver variability’s.
PMCID: PMC4178958  PMID: 25279273
PVI; Thrombus; LAA; Volumes
5.  Cost-effectiveness of cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary artery disease in Germany 
Recent studies have demonstrated a superior diagnostic accuracy of cardiovascular magnetic resonance (CMR) for the detection of coronary artery disease (CAD). We aimed to determine the comparative cost-effectiveness of CMR versus single-photon emission computed tomography (SPECT).
Based on Bayes’ theorem, a mathematical model was developed to compare the cost-effectiveness and utility of CMR with SPECT in patients with suspected CAD. Invasive coronary angiography served as the standard of reference. Effectiveness was defined as the accurate detection of CAD, and utility as the number of quality-adjusted life-years (QALYs) gained. Model input parameters were derived from the literature, and the cost analysis was conducted from a German health care payer’s perspective. Extensive sensitivity analyses were performed.
Reimbursement fees represented only a minor fraction of the total costs incurred by a diagnostic strategy. Increases in the prevalence of CAD were generally associated with improved cost-effectiveness and decreased costs per utility unit (ΔQALY). By comparison, CMR was consistently more cost-effective than SPECT, and showed lower costs per QALY gained. Given a CAD prevalence of 0.50, CMR was associated with total costs of €6,120 for one patient correctly diagnosed as having CAD and with €2,246 per ΔQALY gained versus €7,065 and €2,931 for SPECT, respectively. Above a threshold value of CAD prevalence of 0.60, proceeding directly to invasive angiography was the most cost-effective approach.
In patients with low to intermediate CAD probabilities, CMR is more cost-effective than SPECT. Moreover, lower costs per utility unit indicate a superior clinical utility of CMR.
PMCID: PMC3688498  PMID: 23574690
Cost-effectiveness; Cardiovascular magnetic resonance; Scintigraphy; Coronary angiography; Coronary artery disease
6.  Rationale, objectives, and design of the EUTrigTreat clinical study: a prospective observational study for arrhythmia risk stratification and assessment of interrelationships among repolarization markers and genotype 
Europace  2011;14(3):416-422.
The EUTrigTreat clinical study has been designed as a prospective multicentre observational study and aims to (i) risk stratify patients with an implantable cardioverter defibrillator (ICD) for mortality and shock risk using multiple novel and established risk markers, (ii) explore a link between repolarization biomarkers and genetics of ion (Ca2+, Na+, K+) metabolism, (iii) compare the results of invasive and non-invasive electrophysiological (EP) testing, (iv) assess changes of non-invasive risk stratification tests over time, and (v) associate arrythmogenomic risk through 19 candidate genes.
Methods and results
Patients with clinical ICD indication are eligible for the trial. Upon inclusion, patients will undergo non-invasive risk stratification, including beat-to-beat variability of repolarization (BVR), T-wave alternans, T-wave morphology variables, ambient arrhythmias from Holter, heart rate variability, and heart rate turbulence. Non-invasive or invasive programmed electrical stimulation will assess inducibility of ventricular arrhythmias, with the latter including recordings of monophasic action potentials and assessment of restitution properties. Established candidate genes are screened for variants. The primary endpoint is all-cause mortality, while one of the secondary endpoints is ICD shock risk. A mean follow-up of 3.3 years is anticipated. Non-invasive testing will be repeated annually during follow-up. It has been calculated that 700 patients are required to identify risk predictors of the primary endpoint, with a possible increase to 1000 patients based on interim risk analysis.
The EUTrigTreat clinical study aims to overcome current shortcomings in sudden cardiac death risk stratification and to answer several related research questions. The initial patient recruitment is expected to be completed in July 2012, and follow-up is expected to end in September 2014. identifier: NCT01209494.
PMCID: PMC3283222  PMID: 22117037
Sudden cardiac death risk stratification; Implantable cardioverter defibrillator; Cardiomyocyte ion metabolism; Ventricular repolarization; Electrocardiogram; Programmed electrical stimulation; Repolarization alternans
7.  AMPK - Activated Protein Kinase and its Role in Energy Metabolism of the Heart 
Current Cardiology Reviews  2010;6(4):337-342.
Adenosine monophosphate – activated kinase (AMPK) plays a key role in the coordination of the heart’s anabolic and catabolic pathways. It induces a cellular cascade at the center of maintaining energy homeostasis in the cardiomyocytes.. The activated AMPK is a heterotrimeric protein, separated into a catalytic α - subunit (63kDa), a regulating β - subunit (38kDa) and a γ - subunit (38kDa), which is allosterically adjusted by adenosine triphosphate (ATP) and adenosine monophosphate (AMP). The actual binding of AMP to the γ – subunit is the step which activates AMPK.
AMPK serves also as a protein kinase in several metabolic pathways of the heart, including cellular energy sensoring or cardiovascular protection. The AMPK cascade represents a sensitive system, activated by cellular stresses that deplete ATP and acts as an indicator of intracellular ATP/AMP. In the context of cellular stressors (i.e. hypoxia, pressure overload, hypertrophy or ATP deficiency) the increasing levels of AMP promote allosteric activation and phosphorylation of AMPK. As the concentration of AMP begins to increase, ATP competitively inhibits further phosphorylation of AMPK. The increase of AMP may also be induced either from an iatrogenic emboli, percutaneous coronary intervention, or from atherosclerotic plaque rupture leading to an ischemia in the microcirculation. To modulate energy metabolism by phosphorylation and dephosphorylation is vital in terms of ATP usage, maintaining transmembrane transporters and preserving membrane potential.
In this article, we review AMPK and its role as an important regulatory enzyme during periods of myocardial stress, regulating energy metabolism, protein synthesis and cardiovascular protection.
PMCID: PMC3083815  PMID: 22043210
Adenosine monophosphate - activated protein kinase; AMPK; heart failure; cardiac energy metabolism.
8.  Value of the BI-RADS classification in MR-Mammography for diagnosis of benign and malignant breast tumors 
European Radiology  2011;21(12):2475-2483.
To assess whether the BI-RADS classification in MR-Mammography (MRM) can distinguish between benign and malignant lesions.
Material and method
207 MRM investigations were categorised according to BI-RADS. The results were compared to histology. All MRM studies were interpreted by two examiners. Statistical significance for the accuracy of MRM was calculated.
A significant correlation between specific histology and MRM-tumour-morphology could not be reported. Mass (68%) was significant for malignancy. Significance raised with irregular shape (88%), spiculated margin (97%), rim enhancement (98%), fast initial increase (90%), post initial plateau (65%), and intermediate T2 result (82%). Highly significant for benignity was an oval mass (79%), slow initial increase (94%) and a hyperintense T2 result (77%), also an inconspicuous MRM result (77%) was often seen in benign histology. Symmetry (90%) and further post initial increase (90%) were significant, whereas a regional distribution (74%) was lowly significant for benignity.
On basis of the BI-RADS classification an objective comparability and statement of diagnosis could be made highly significant. Due to the fact of false-negative and false-positive MRM-results, histology is necessary.
PMCID: PMC3217139  PMID: 21805368
Magnetic resonance imaging; Breast tumours; Breast cancer
9.  Remote magnetic versus manual catheter navigation for circumferential pulmonary vein ablation in patients with atrial fibrillation 
Clinical Research in Cardiology  2011;100(11):1003-1011.
Only limited data exist on the clinical utility of remote magnetic navigation (RMN) for pulmonary vein (PV) ablation. Aim of this prospective study was to evaluate the safety and efficacy of RMN for PV isolation as compared to the manual (CON) approach.
Methods and results
A total of 161 consecutive patients undergoing circumferential PV isolation were included. Open-irrigated 3.5 mm ablation catheters under the guidance of a mapping system were used. The catheter was navigated with the Stereotaxis Niobe II system in the RMN group (n = 107) and guided manually in the CON group (n = 54). Electrical isolation of all PVs was achieved in 90% of the patients in the RMN group and in 87% in the CON group (p = 0.6). All subjects were followed every 3 months by 7d Holter-ECG. At 12 months of follow-up, 53.5% (RMN) and 55.5% (CON) of the patients were free of any left atrial tachycardia/atrial fibrillation (AF) episode (p = 0.57). Free of symptomatic AF recurrence were 66.3% (RMN) and 62.1% (CON) of the subjects (p = 0.80). Use of RMN was associated with longer procedure duration (p < 0.0001), ablation times (p < 0.0001), and RF current application duration (p < 0.05). In contrast, fluoroscopy time was lower in the RMN group (p < 0.0001). Major complications occurred in 6 of 161 procedures (3.7%), with no significant difference between groups (p = 0.75).
RMN-guided PV ablation provides comparable acute and long-term success rates as compared to manual navigation. Procedural complication rates are similar. The use of RMN is associated with markedly reduced fluoroscopy time, but prolonged ablation and procedure duration.
PMCID: PMC3203998  PMID: 21706198
Ablation; Electrophysiology; Atrial fibrillation; Pulmonary vein ablation; Remote magnetic navigation
10.  MDCT in the diagnostic algorithm in patients with symptomatic atrial fibrillation 
World Journal of Radiology  2011;3(2):41-46.
Atrial fibrillation (AF) is the most common supraventricular arrhythmia and a major cause of morbidity. Arrhythmogenic foci originating within the pulmonary veins (PVs) are an important cause of both paroxysmal and persistent AF. A variety of endovascular and surgical techniques have been used to electrically isolate the PV from the left atrium. Pulmonary venography for localization of the PV ostium can be difficult to perform during the ablation procedure. While the anatomy of the PV is patient-specific, non-invasive imaging techniques may provide useful diagnostic information prior to the intended intervention. In this context, multidetector computed tomography (MDCT) visualization of the left atrial and PV anatomy prior to left atrial ablation and PV isolation is becoming increasingly important. MDCT imaging provides pre-procedural information on the left atrial anatomy, including atrial size and venous attachments, and it may identify potential post-procedural complications, such as pulmonary vein stenosis or cardiac perforations. Here, we review the relevant literature and present the current “state-of-the-art” of left atrial anatomy, PV ostia as well as the clinical aspects of refractory AF, MDCT imaging protocols and procedural aspects of PV ablation.
PMCID: PMC3051109  PMID: 21390192
Atrial fibrillation; Multidetector computed tomography; Pulmonary veins; Pulmonary vein ablation
12.  Extra cardiac findings by 64-multidetector computed tomography in patients with symptomatic atrial fibrillation prior to pulmonal vein isolation 
The aim of this study was to investigate the prevalence of extracardiac findings diagnosed by 64-multidetector computed tomography (MDCT) examinations prior to circumferential pulmonary vein (PV) ablation of atrial fibrillation (AF). A total of 158 patients (median age, 60.5 years; male 68%) underwent 64-MDCT of the chest and upper abdomen to characterize left atrial and PV anatomy prior to AF ablation. MDCT images were evaluated by a thoracic radiologist and a cardiologist. For additional scan interpretation, bone, lung, and soft tissue window settings were used. CT scans with extra-cardiac abnormalities categorized for the anatomic distribution and divided into two groups: Group 1—exhibiting clinically significant or potentially significant findings, and Group 2—patients with clinically non-significant findings. Extracardiac findings (n = 198) were observed in 113/158 (72%) patients. At least one significant finding was noted in 49/158 patients (31%). Group 1 abnormalities, such as malignancies or pneumonias, were found in 85/198 findings (43%). Group 2 findings, for example mild degenerative spine disease or pleural thickening, were observed in 113/198 findings (72%). 74/198 Extracardiac findings were located in the lung (37%), 35/198 in the mediastinum (18%), 8/198 into the liver (4%) and 81/198 were in other organs (41). There is an appreciable prevalence of prior undiagnosed extracardiac findings detected in patients with AF prior to PV-Isolation by MDCT. Clinically significant or potentially significant findings can be expected in ~40% of patients who undergo cardiac MDCT. Interdisciplinary trained personnel is required to identify and interpret both cardiac and extra cardiac findings.
PMCID: PMC3035788  PMID: 20549365
Extra cardiac findings; Atrial fibrillation; 64-MDCT; Pulmonary vein ablation
13.  Bentall procedure 39 years after implantation of a Starr-Edwards Aortic Caged- Ball-Valve Prosthesis 
We report a case of a male patient who received an implantation of a Starr-Edwards-caged-ball-valve-prosthesis in 1967. The surgery and postoperative course were without complications and the patient recovered well after the operation. For the next four decades, the patient remained asymptomatic - no restrictions on his lifestyle and without any complications. In 2006, 39 years after the initial operation, we performed a Bentall-Procedure to treat an aortic ascendens aneurysm with diameters of 6.0 × 6.5 cm: we explanted the old Starr-Edwards-aortic-caged-ball-valve-prosthesis and replaced the ascending aorta with a 29 mm St.Jude Medical aortic-valve-composite-graft and re-implanted the coronary arteries.
This case represents the longest time period between Starr-Edwards-caged-ball-valve-prothesis-implantation and Bentall-reoperation, thereby confirming the excellent durability of this valve.
PMCID: PMC2848035  PMID: 20298579
14.  Visualization of transcoronary ablation of septal hypertrophy in patients with hypertrophic obstructive cardiomyopathy: a comparison between cardiac MRI, invasive measurements and echocardiography 
Clinical Research in Cardiology  2010;99(6):359-368.
Hypertrophic obstructive cardiomyopathy (HOCM) is treated by surgical myectomy or transcoronary ablation of septal hypertrophy (TASH). The aim of this study was to visualize the feasibility, success and short-term results of TASH on the basis of cardiac MRI (CMR) in comparison with cardiac catheterization and echocardiography.
In this in vivo study, nine patients with HOCM were treated with TASH. Patients were evaluated by transthoracic echocardiography, invasive cardiac angiography and CMR. Follow-up examinations were carried out after 1, 3 and 12 months. MR imaging was performed on a 1.5-T scanner. All images were processed using the semiautomatic Argus software and were evaluated by an attending thoracic radiologist and cardiologist.
The echocardiographic pressure gradient (at rest) was 69.3 ± 15.3 mmHg before and 22.1 ± 5.7 mmHg after TASH (P < 0.01, n = 9). The flux acceleration over the aortic valve examined (Vmax) was 5.1 ± 0.6 m/s before and 3.4 ± 0.3 m/s after the TASH procedure (P < 0.05). Also, there was a decrease of septum thickness from 22.0 ± 1.2 to 20.2 ± 1.0 mm (P < 0.05) after 6 ± 3 weeks. The invasively assessed pressure gradient at rest was reduced from 63.7 ± 15.2 to 21.2 ± 11.1 mmHg (P < 0.01) and the post-extrasystolic gradient was reduced from 138.9 ± 12.7 to 45.6 ± 16.5 mmHg (P < 0.01). All differences as well as the quantity of injected ethanol were plotted against the size or amount of scar tissue as assessed in the MRI. There was a statistically significant correlation between the post-extrasystolic gradient decrease and the amount of scar tissue (P = 0.03, r2 = 0.5). In addition, the correlation between the quantity of ethanol and scar tissue area was highly significant (P < 0.01, r2 = 0.6), whereas the values for the gradient deviation (P = 0.10, r2 = 0.34), ΔVmax (P = 0.12, r2 = 0.31), as well as the gradient at rest (P = 0.27, r2 = 0.17) were not significant.
TASH was consistently effective in reducing the gradient in all patients with HOCM. In contrast to the variables investigated by echocardiography, the invasively measured post-extrasystolic gradient correlated much better with the amount of scar tissue as assessed by CMR. We conclude that the optimal modality to visualize the TASH effect seems to be a combination of CMR and the invasive identification of the post-extrasystolic gradient.
PMCID: PMC2876266  PMID: 20503122
HOCM; TASH; CMR; Cardiac imaging
15.  Impact of Breast Density on Computer-Aided Detection in Full-Field Digital Mammography 
Journal of Digital Imaging  2006;19(3):258-263.
The goal of this study was to evaluate the performance of a computer-aided detection (CAD) system in full-field digital mammography (Senographe 2000D, General Electric, Buc, France) in finding out carcinomas depending on the parenchymal density. A total of 226 mediolateral oblique (MLO) and 186 craniocaudal (CC) mammographic views of histologically proven cancers were retrospectively evaluated with a digital CAD system (ImageChecker V2.3 R2 Technology, Los Altos, CA, USA). Malignant tumors were detected correctly by CAD in MLO view in 84.85% in breasts with parenchymal tissue density of the American College of Radiology (ACR) type 1, in 70.33% of the ACR type 2, in 68.12% of the ACR type 3, and in 69.70% of the ACR type 4. For the CC view, similar results were found according to the ACR types. Using the chi-square and McNemar tests, there was no statistical significance. However, a trend of better detection could be seen with decreasing ACR type. In conclusion, there seems to be a tendency for breast tissue density to affect the detection rate of breast cancer when using the CAD system.
PMCID: PMC3045151  PMID: 16741664
Full-field digital mammography; computer-aided detection (CAD); breast density; ACR types
16.  Effects of Ranolazine on Torsades de Pointes Tachycardias in a Healthy Isolated Rabbit Heart Model 
Cardiovascular Therapeutics  2014;32(4):170-177.
Torsades de pointes (TdP) tachycardias are triggered, polymorphic ventricular arrhythmias arising from early afterdepolarizations (EADs) and increased dispersion of repolarization. Ranolazine is a new agent which reduces pathologically elevated late INa but also IKr. Aim of this study was to evaluate the effects of ranolazine in a validated isolated Langendorff-perfused rabbit heart model.
TdP was reproducibly induced with d-sotalol (10−4 mol/L) and low potassium (K) (1.0 mmol/L for 5 min, pacing at CL 1000 ms). In 10 hearts, ECG and 8 epi- and endocardial monophasic action potentials were recorded. Action potential duration (APD) was measured at 90% repolarization and dispersion defined as APD max–min.
D-sotalol prolonged APD90 and increased dispersion of APD90, simultaneously causing EADs and induction of TdP. The combination of d-sotalol and two concentrations of ranolazine did not increase dispersion of ventricular APD90 as compared to vehicle. Ranolazine at 5 μmol/L did not cause additional induction of EADs and/or TdP but also did not significantly suppress arrhythmogenic triggers. The higher concentration of ranolazine (10 μmol/L) in combination with d-sotalol caused further prolongation of APD90, at the same time reduction in APD90 dispersion. In parallel, the incidence of EADs was reduced and an antitorsadogenic effect was seen.
In the healthy isolated rabbit heart (where late INa is not elevated), ranolazine does not cause proarrhythmia but exerts antiarrhythmic effects in a dose-dependent manner against d-sotalol/low K-induced TdP. This finding—despite additional APD prolongation—supports the safety of a combined use of both drugs and merits clinical investigation.
PMCID: PMC4285941  PMID: 24785406

Results 1-16 (16)