Matthias Daniel Zink

Automatic Detection of Atrial Fibrillation in Cardiac Vibration Signals

We present a study on the feasibility of the automatic detection of atrial fibrillation (AF) from cardiac vibration signals (ballistocardiograms/BCGs) recorded by unobtrusive bed-mounted sensors. The proposed system is intended as a screening and monitoring tool in home-healthcare applications and not as a replacement for ECG-based methods used in clinical environments. Based on the BCG data recorded in a study with ten AF patients, we evaluate and rank seven popular machine learning algorithms (naive Bayes, linear and quadratic discriminant analysis, support vector machines, random forests as well as bagged and boosted trees) for their performance in separating 30-s long BCG epochs into one of three classes: sinus rhythm, AF, and artifact. For each algorithm, feature subsets of a set of statistical time-frequency-domain and time-domain features were selected based on the mutual information between features and class labels as well as the first- and second-order interactions among features. The classifiers were evaluated on a set of 856 epochs by means of tenfold cross validation. The best algorithm (random forests) achieved a Matthews correlation coefficient, mean sensitivity, and mean specificity of 0.921, 0.938, and 0.982, respectively.

Bioelectrical impedance spectroscopy as a fluid management system in heart failure

Episodes of hospitalization for heart failure patients are frequent and are often accompanied by fluid accumulations. The change of the body impedance, measured by bioimpendace spectroscopy, is an indicator of the water content. The hypothesis was that it is possible to detect edema from the impedance data. First, a finite integration technique was applied to test the feasibility and allowed a theoretical analysis of current flows through the body. Based on the results of the simulations, a clinical study was designed and conducted. The segmental impedances of 25 patients suffering from heart failure were monitored over their recompensation process. The mean age of the patients was 73.8 and their mean body mass index was 28.6. From these raw data the model parameters from the Cole model were deduced by an automatic fitting algorithm. These model data were used to classify the edema status of the patient. The baseline values of the regression lines of the extra- and intracellular resistance from the transthoracic measurement and the baseline value of the regression line of the extracellular resistance from the foot-to-foot measurement were identified as important parameters for the detection of peripheral edema. The rate of change of the imaginary impedance at the characteristic frequency and the mean intracellular resistance from the foot-to-foot measurement were identified as important parameters for the detection of pulmonary edema. To classify the data, two decision trees were considered: One should detect pulmonary edema (n(pulmonary) = 13, n(none) = 12) and the other peripheral edema (n(peripheral) = 12, n(none) = 13). Peripheral edema could be detected with a sensitivity of 100% and a specificity of 90%. The detection of pulmonary edema showed a sensitivity of 92.31% and a specificity of 100%. The leave-one-out cross-validation-error for the peripheral edema detection was 12% and 8% for the detection of pulmonary edema. This enables the application of BIS as an early warning system for cardiac decompensation with the potential to optimize patient care.

Electromagnetic Interference With Implantable Cardioverter-Defibrillators at Power Frequency An In Vivo Study

Background— The number of implantable cardioverter-defibrillators (ICDs) for the prevention of sudden cardiac death is continuing to increase. Given the technological complexity of ICDs, it is of critical importance to identify and control possible harmful electromagnetic interferences between various sources of electromagnetic fields and ICDs in daily life and occupational environments. Methods and Results— Interference thresholds of 110 ICD patients (1-, 2-, and 3-chamber ICDs) were evaluated in a specifically developed test site. Patients were exposed to single and combined electric and magnetic 50-Hz fields with strengths of up to 30 kV·m−1 and 2.55 mT. Tests were conducted considering worst-case conditions, including maximum sensitivity of the device or full inspiration. With devices being programmed to nominal sensitivity, ICDs remained unaffected in 91 patients (83%). Five of 110 devices (5%) showed transient loss of accurate right ventricular sensing, whereas 14 of 31 (45%) of the 2- and 3-chamber devices displayed impaired right atrial sensing. No interference was detected in 71 patients (65%) within the tested limits with programming to maximum sensitivity, whereas 20 of 110 subjects (18%) exhibited right ventricular disturbances and 19 of 31 (61%) subjects exhibited right atrial disturbances. Conclusions— Extremely low-frequency daily-life electromagnetic fields do not disturb sensing capabilities of ICDs. However, strong 50-Hz electromagnetic fields, present in certain occupational environments, may cause inappropriate sensing, potentially leading to false detection of atrial/ventricular arrhythmic events. When the right atrial/right ventricular interferences are compared, the atrial lead is more susceptible to electromagnetic fields. Clinical Trial Registration— URL: http://clinicaltrials.gov/ct2/show/NCT01626261. Unique identifier: NCT01626261.

Chronic Electrical Neuronal Stimulation Increases Cardiac Parasympathetic Tone by Eliciting Neurotrophic Effects

Rationale: Recently, we provided a technique of chronic high-frequency electric stimulation (HFES) of the right inferior ganglionated plexus for ventricular rate control during atrial fibrillation in dogs and humans. In these experiments, we observed a decrease of the intrinsic ventricular rate during the first 4 to 5 months when HFES was intermittently shut off. Objective: We thus hypothesized that HFES might elicit trophic effects on cardiac neurons, which in turn increase baseline parasympathetic tone of the atrioventricular node. Methods and Results: In mongrel dogs atrial fibrillation was induced by rapid atrial pacing. Endocardial HFES of the right inferior ganglionated plexus, which contains abundant fibers to the atrioventricular node, was performed for 2 years. Sham-operated nonstimulated dogs served as control. In chronic neurostimulated dogs, we found an increased neuronal cell size accompanied by an increase of choline acetyltransferase and unchanged tyrosine hydroxylase protein expression as compared with unstimulated dogs. Moreover, &bgr;-nerve growth factor (NGF) and neurotrophin (NT)-3 were upregulated in chronically neurostimulated dogs. In vitro, HFES of cultured neurons of interatrial ganglionated plexus from adult rats increased neuronal growth accompanied by upregulation of NGF, NT-3, glial-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) expression. NGF was identified as the main growth-inducing factor, whereas NT-3 did not affect HFES-induced growth. However, NT-3 could be identified as an important acetylcholine-upregulating factor. Conclusions: HFES of cardiac neurons in vivo and in vitro causes neuronal cellular hypertrophy, which is mediated by NGF and boosters cellular function by NT-3–mediated acetylcholine upregulation. This knowledge may contribute to develop HFES techniques to augment cardiac parasympathetic tone.

Mechanical stretch of sympathetic neurons induces VEGF expression via a NGF and CNTF signaling pathway.

Mechanical stretch has been shown to increase vascular endothelial growth factor (VEGF) expression in cultured myocytes. Sympathetic neurons (SN) also possess the ability to express and secrete VEGF, which is mediated by the NGF/TrkA signaling pathway. Recently, we demonstrated that SN respond to stretch with an upregulation of nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF). Whether stretch increases neuronal VEGF expression still remains to be clarified. Therefore, SN from the superior cervical ganglia of neonatal Sprangue Dawley rats were exposed to a gradual increase of stretch from 3% up to 13% within 3days (3%, 7% and 13%). Under these conditions, the expression and secretion of VEGF was analyzed. Mechanical stretch significantly increased VEGF mRNA and protein expression (mRNA: control=1 vs. stretch=3.1; n=3/protein: control=1 vs. stretch=2.7; n=3). ELISA experiments to asses VEGF content in the cell culture supernatant showed a time and dose dependency in VEGF increment due to stretch. NGF and CNTF neutralization decreased stretch-induced VEGF augmentation in a significant manner. This response was mediated in part by TrkA receptor activation. The stretch-induced VEGF upregulation was accompanied by an increase in HIF-1α expression. KDR levels remained unchanged under conditions of stretch, but showed a significant increase due to NGF neutralization. In summary, SN respond to stretch with an upregulation of VEGF, which is mediated by the NGF/CNTF and TrkA signaling pathway paralleled by HIF-1α expression. NGF signaling seems to play an important role in regulating neuronal KDR expression.

Rate and irregularity of electrical activation during atrial fibrillation affect myocardial NGF expression via different signalling routes

An irregular ventricular response during atrial fibrillation (AF) has been shown to mediate an increase in sympathetic nerve activity in human subjects. The molecular mechanisms remain unclear. This study aimed to investigate the impact of rate and irregularity on nerve growth factor (NGF) expression in cardiomyocytes, since NGF is known to be the main contributor to cardiac sympathetic innervation density. Cell cultures of neonatal rat ventricular myocytes were electrically stimulated for 48 h with increasing rates (0, 5 and 50 Hz) and irregularity (standard deviation (SD)=5%, 25% and 50% of mean cycle length). Furthermore, we analyzed the calcineurin-NFAT and the endothelin-1 signalling pathways as possible contributors to NGF regulation during arrhythmic stimulation. We found that the increase of NGF expression reached its maximum at the irregularity of 25% SD by 5 Hz (NGF: 5 Hz 0% SD=1 vs. 5Hz 25% SD=1.57, P<0.05). Specific blockade of the ET-A receptor by BQ123 could abolish this NGF increase (NGF: 5 Hz 25% SD+BQ123=0.66, P<0.05). High frequency electrical field stimulation (HFES) with 50 Hz decreased the NGF expression in a significant manner (NGF: 50Hz=0.55, P<0.05). Inhibition of calcineurin-NFAT signalling with cyclosporine-A or 11R-VIVIT abolished the HFES induced NGF down-regulation (NGF: 50 Hz+CsA=1.14, P<0.05). In summary, this study reveals different signalling routes of NGF expression in cardiomyocytes exposed to increasing rates and irregularity. Whether this translates into different degrees of NGF expression and possibly neural sympathetic growth in various forms of ventricular rate control during AF remains to be elucidated in further studies.

Effect of lead position and orientation on electromagnetic interference in patients with bipolar cardiovascular implantable electronic devices

Aims Electromagnetic interferences (EMIs) with cardiovascular implantable electronic devices (CIEDs) are associated with potential risk for patients. Studies imply that CIED sensitivity setting and leads tip‐to‐ring spacing determine the susceptibility of CIEDs with bipolar leads to electric and magnetic fields (EMFs); however, little is known about additional decisive parameters affecting EMI of CIEDs. We therefore investigated the influence of different patient‐, device‐, and lead‐depending variables on EMIs in 160 patients. Methods and results We ran numerical simulations with human models to determine lead‐depending variables on the risk of EMI by calculating the voltage induced in bipolar leads from 50/60 Hz EMF. We then used the simulation results and analysed 26 different patient‐, device‐, and lead‐depending variables with respect to the EMI threshold of 160 CIED patients. Our analyses revealed that a horizontal orientation and a medial position of the bipolar leads distal end (lead‐tip) are most beneficial for CIED patients to reduce the risk of EMI. In addition, the effect of CIED sensitivity setting and leads tip‐to‐ring spacing was confirmed. Conclusion Our data suggest that in addition to the established influencing factors, a medial position of the lead‐tip for the right ventricular lead as achievable at the interventricular septum and a horizontal orientation of the lead‐tip can reduce the risk of EMI. In the right atrium, a horizontal orientation of the lead‐tip should generally be striven independent of the chosen position. Still important to consider remains a good intrinsic sensing amplitude during implant procedure.

Heartbeat Cycle Length Detection by a Ballistocardiographic Sensor in Atrial Fibrillation and Sinus Rhythm

Background. Heart rate monitoring is especially interesting in patients with atrial fibrillation (AF) and is routinely performed by ECG. A ballistocardiography (BCG) foil is an unobtrusive sensor for mechanical vibrations. We tested the correlation of heartbeat cycle length detection by a novel algorithm for a BCG foil to an ECG in AF and sinus rhythm (SR). Methods. In 22 patients we obtained BCG and synchronized ECG recordings before and after cardioversion and examined the correlation between heartbeat characteristics. Results. We analyzed a total of 4317 heartbeats during AF and 2445 during SR with a correlation between ECG and BCG during AF of r = 0.70 (95% CI 0.68–0.71, P < 0.0001) and r = 0.75 (95% CI 0.73–0.77, P < 0.0001) during SR. By adding a quality index, artifacts could be reduced and the correlation increased for AF to 0.76 (95% CI 0.74–0.77, P < 0.0001, n = 3468) and for SR to 0.85 (95% CI 0.83–0.86, P < 0.0001, n = 2176). Conclusion. Heartbeat cycle length measurement by our novel algorithm for BCG foil is feasible during SR and AF, offering new possibilities of unobtrusive heart rate monitoring. This trial is registered with IRB registration number EK205/11. This trial is registered with clinical trials registration number NCT01779674.

Feasibility of Bioelectrical Impedance Spectroscopy Measurement before and after Thoracentesis

Background. Bioelectrical impedance spectroscopy is applied to measure changes in tissue composition. The aim of this study was to evaluate its feasibility in measuring the fluid shift after thoracentesis in patients with pleural effusion. Methods. 45 participants (21 with pleural effusion and 24 healthy subjects) were included. Bioelectrical impedance was analyzed for “Transthoracic,” “Foot to Foot,” “Foot to Hand,” and “Hand to Hand” vectors in low and high frequency domain before and after thoracentesis. Healthy subjects were measured at a single time point. Results. The mean volume of removed pleural effusion was 1169 ± 513 mL. The “Foot to Foot,” “Hand to Hand,” and “Foot to Hand” vector indicated a trend for increased bioelectrical impedance after thoracentesis. Values for the low frequency domain in the “Transthoracic” vector increased significantly (P < 0.001). A moderate correlation was observed between the amount of removed fluid and impedance change in the low frequency domain using the “Foot to Hand” vector (r = −0.7). Conclusion. Bioelectrical impedance changes in correlation with the thoracic fluid level. It was feasible to monitor significant fluid shifts and loss after thoracentesis in the “Transthoracic” vector by means of bioelectrical impedance spectroscopy. The trial is registered with Registration Numbers IRB EK206/11 and NCT01778270.

Individualized biomonitoring in heart failure--Biomon-HF "Keep an eye on heart failure--especially at night".

Abstract In the project “Individualized Biomonitoring in Heart Failure (Biomon-HF),” innovative sensors and algorithms for measuring vital signs, i.e., during the nocturnal sleep period, have been developed and successfully tested in five clinical feasibility studies involving 115 patients. The Biomon-HF sensor concepts are an important step toward future patient-customized telemonitoring and sensor-guided therapy management in chronic heart failure, including early detection of upcoming HF exacerbation and comorbidities at home. The resulting preventable disease complications and emergencies and reduction of consequences of disease are very important advantages for the patients, causing relief for medical staff and, thus, offer an enormous potential for improvements and cost savings in healthcare systems.