A Robot Mimicking Heart Motions: An Ex-Vivo Test Approach for Cardiac Devices.

PURPOSE: The pre-clinical testing of cardiovascular implants gains increasing attention due to the complexity of novel implants and new medical device regulations. It often relies on large animal experiments that are afflicted with ethical and methodical challenges. Thus, a method for simulating physiological heart motions is desired but lacking so far. METHODS: We developed a robotic platform that allows simulating the trajectory of any point of the heart (one at a time) in six degrees of freedom. It uses heart motion trajectories acquired from cardiac magnetic resonance imaging or accelero-meter data. The rotations of the six motors are calculated based on the input trajectory. A closed-loop controller drives the platform and a graphical user interface monitors the functioning and accuracy of the robot using encoder data. RESULTS: The robotic platform can mimic physiological heart motions from large animals and humans. It offers a spherical work envelope with a radius of 29 mm, maximum acceleration of 20 m/s2 and maximum deflection of ±19° along all axes. The absolute mean positioning error in x-, y- and z-direction is 0.21 ±0.06, 0.31 ±0.11 and 0.17 ±0.12 mm, respectively. The absolute mean orientation error around x-, y- and z-axis (roll, pitch and yaw) is 0.24 ±0.18°, 0.23 ±0.13° and 0.18 ±0.18°, respectively. CONCLUSION: The novel robotic approach allows reproducing heart motions with high accuracy and repeatability. This may benefit the device development process and allows re-using previously acquired heart motion data repeatedly, thus avoiding animal trials.

Mitral valve repair with a device for artificial chordal implantation at 2 years.

Objectives: This study examines the early and midterm safety, efficacy, and durability of mitral valve repair for primary mitral regurgitation (MR) using the ChordArt device (CoreMedic) for chordal replacement. Methods: Five patients with symptomatic severe primary degenerative MR due to isolated central posterior leaflet prolapse/flail were treated with the ChordArt device in a transseptal surgical approach and followed prospectively with periodical clinical and echocardiographic assessments for 2 years. Results: Reduction of MR immediately after the implantation of artificial chords was achieved in all patients showing no or trace MR (<1+/4+). In all patients, MR <1+ was maintained during 24 months of follow-up. No dehiscence, detachment, or dislocation of the implanted ChordArt devices was observed. Transthoracic echocardiography showed that left ventricle end diastolic diameter significantly decreased during the whole follow-up period in comparison to baseline condition, especially at discharge and 1-month follow-up. Left ventricle end systolic diameter also significantly decreased during the whole follow-up period in comparison to baseline condition. Left atrial volume significantly decreased during the follow-up period in comparison to discharge. No major adverse events, as defined per protocol, were observed during the intervention or during the follow-up period. Conclusions: The ChordArt device allows successful treatment of primary degenerative MR due to posterior mitral leaflet prolapse or flail, with a good safety profile and promising immediate clinical and echocardiographic benefits that are confirmed up to 24 months.

Automated Implantation of Artificial Mitral Chords: Preliminary Results From the Feasibility Trial.

PURPOSE: A novel chordal system enables automated implantation of artificial mitral chords to treat mitral regurgitation (MR). This article summarizes the first-in-man initial clinical results. DESCRIPTION: The CHAGALL (CHordArt system study for the treatment of mitral ReGurgitAtion due to leaflet proLapse or fLail) trial is a single arm, multicenter, prospective study to test the feasibility of this system for mitral repair. The interim clinical and echocardiographic results of the first 5 patients with a 12-month follow-up are presented. EVALUATION: Five patients (mean age, 64 years) with severe MR received implantation of neochords with this device under cardiopulmonary bypass. Technical success was obtained in all patients. Transesophageal echocardiogram showed either no or trace residual MR (<1+/4+) after repair. Survival at 30 days was 100%, and no device-related complication occurred. Reduction of MR was sustained up to 12 months. CONCLUSIONS: This novel chordal system is promising because it greatly facilitates the deployment of neochords to repair the mitral valve. Results at 12 months are encouraging. The device is currently under development for transcatheter approach.

Coronary wave intensity patterns in stable coronary artery disease: influence of stenosis severity and collateral circulation.

Objective: Wave intensity analysis is a method that allows separating pulse waves into components generated proximally and in the periphery of arterial trees, as well as characterising them as accelerating or decelerating. The early diastolic suction wave (eaDSW) is one of the most prominent wave events in the coronaries. The aim of this study was to determine whether (1) microvascular dilatation directly influences its energy, (2) stenosis severity can be assessed proximal to stenoses, (3) distal pulse wave entrapment exists in the presence of stenoses and (4) coronary collaterals influence wave entrapment. Methods: In 43 coronary artery disease patients, Doppler flow velocity and pressure measurements were performed in a proximal coronary segment at rest, in a distal segment at rest, during adenosine-induced hyperaemia and during balloon occlusion. Wave energies were calculated as the area under the wave intensity curves. Results: The eaDSW energy showed a significant increase during hyperaemia, but did not differ between proximal and distal segments. There was no significant correlation between eaDSW energy and coronary stenosis severity. Pulse wave entrapment could not be observed consistently in the distal segments. Consequently, the effect of coronary collaterals on pulse wave entrapment could not be studied. Conclusions: Microvascular dilation in the coronary circulation increases distal eaDSW energy. However, it does not show any diagnostically useful variation between measurement sites, various stenosis degrees and amount of collateral flow. The assessment eaDSW and its reflections were not useful for the quantification of coronary stenosis severity or the collateral circulation in clinical practice.

Endocardial Energy Harvesting by Electromagnetic Induction.

OBJECTIVE: cardiac pacemakers require regular medical follow-ups to ensure proper functioning. However, device replacements due to battery depletion are common and account for ∼25% of all implantation procedures. Furthermore, conventional pacemakers require pacemaker leads which are prone to fractures, dislocations or isolation defects. The ensuing surgical interventions increase risks for the patients and costs that need to be avoided. METHODS: in this study, we present a method to harvest energy from endocardial heart motions. We developed a novel generator, which converts the heart's mechanical into electrical energy by electromagnetic induction. A mathematical model has been introduced to identify design parameters strongly related to the energy conversion efficiency of heart motions and fit the geometrical constraints for a miniaturized transcatheter deployable device. The implemented final design was tested on the bench and in vivo. RESULTS: the mathematical model proved an accurate method to estimate the harvested energy. For three previously recorded heart motions, the model predicted a mean output power of 14.5, 41.9, and 16.9 µW. During an animal experiment, the implanted device harvested a mean output power of 0.78 and 1.7 µW at a heart rate of 84 and 160 bpm, respectively. CONCLUSION: harvesting kinetic energy from endocardial motions seems feasible. Implanted at an energetically favorable location, such systems might become a welcome alternative to extend the lifetime of cardiac implantable electronic device. SIGNIFICANCE: the presented endocardial energy harvesting concept has the potential to turn pacemakers into battery- and leadless systems and thereby eliminate two major drawbacks of contemporary systems.

Transcatheter mitral valve chord repair.

The field of mitral valve disease diagnosis and management is rapidly evolving. New understanding of pathophysiology and improvements in the adoption of sophisticated multimodality imaging modalities have led to early diagnosis and to more complex treatment. The most common cause of mitral regurgitation (MR) in the western world is in the primary alteration of the valve, which leads to degenerative leaflet prolapse due to chordal elongation or rupture and annular dilatation. Untreated, significant MR has a negative impact prognosis, leading to reduction of survival. In the setting of degenerative MR, surgical repair currently represents the standard of care. Treatment of asymptomatic patients with severe MR in the Valve Center of Excellence, in which successful repair reaches more than 95% and surgical mortality less than 1%, symbolizes the direction for the next years. Transcatheter mitral valve repair with different devices, more recently the chordal replacement ones, is providing good outcomes and became a therapeutic option in high-risk patients with degenerative MR. In the future, more advances are expected from further development of interventional techniques, careful evaluation and better patient selection. This review will focus on long-term surgical outcomes of mitral valve repair with artificial chordae and on the emerging transcatheter chordal repair devices as therapeutic options for degenerative MR patients.

Health care costs of borderline personality disorder and matched controls with major depressive disorder: a comparative study based on anonymized claims data.

BACKGROUND: Borderline personality disorder (BPD) and major depressive disorder (MDD) pose a significant burden to the German health care system in terms of direct and indirect costs. The aim of this study was to determine the incremental costs that arise due to the treatment of patients with BPD, in relation to MDD patients adjusted for gender and age. METHODS: Insured persons who suffered from BPD (F60.3; N = 6599) or MDD (F32, F33; N = 26,396) in the year 2010 were identified from the German Health Risk Institute research database. To estimate the costs resulting from disorder-specific health care service utilization and the mean total costs per patient for the health care system, we analyzed anonymized claims data of individuals with BPD and matched individuals with MDD. RESULTS: The costs resulting from disorder-specific health care service utilization 1 year after index diagnosis amounted to 8508 EUR for BPD and 8281 EUR for MDD per patient utilizing services. With mean total annual costs per patient of 4636 EUR versus 2020 EUR 1 year preceding index diagnosis, 7478 EUR versus 3638 EUR in the year after index diagnosis, and 11,817 EUR versus 6058 EUR 2 years after index diagnosis, BPD patients incurred markedly higher costs. CONCLUSIONS: Since the treatment of BPD causes incremental costs for the German health care system compared to the treatment of MDD, and since both conditions are associated with a high level of suffering, there is a need for establishing adequate and early treatment of these mental disorders.

Towards Batteryless Cardiac Implantable Electronic Devices-The Swiss Way.

Energy harvesting devices are widely discussed as an alternative power source for todays active implantable medical devices. Repeated battery replacement procedures can be avoided by extending the implants life span, which is the goal of energy harvesting concepts. This reduces the risk of complications for the patient and may even reduce device size. The continuous and powerful contractions of a human heart ideally qualify as a battery substitute. In particular, devices in close proximity to the heart such as pacemakers, defibrillators or bio signal (ECG) recorders would benefit from this alternative energy source. The clockwork of an automatic wristwatch was used to transform the hearts kinetic energy into electrical energy. In order to qualify as a continuous energy supply for the consuming device, the mechanism needs to demonstrate its harvesting capability under various conditions. Several in-vivo recorded heart motions were used as input of a mathematical model to optimize the clockworks original conversion efficiency with respect to myocardial contractions. The resulting design was implemented and tested during in-vitro and in-vivo experiments, which demonstrated the superior sensitivity of the new design for all tested heart motions.

Myocardial Microvascular Responsiveness During Acute Cardiac Sympathectomy Induced by Thoracic Epidural Anesthesia.

OBJECTIVE: To evaluate the effect of acute cardiac sympathectomy by thoracic epidural anesthesia on myocardial blood flow and microvascular function. DESIGN: A prospective observational study. SETTING: The study was conducted in a tertiary teaching hospital. PARTICIPANTS: Ten patients with a mean age of 48 years (range 22-63 years) scheduled for thoracic surgery. INTERVENTIONS: Myocardial contrast echocardiography was used to study myocardial blood flow and microvascular responsiveness at rest, during adenosine-induced hyperemia, and after sympathetic stimulation by the cold pressor test. Repeated measurements were performed without and with thoracic epidural anesthesia. MEASUREMENTS AND MAIN RESULTS: An increased myocardial blood volume was observed with thoracic epidural anesthesia compared to baseline (from 0.08±0.02 to 0.10±0.03 mL/mL; p = 0.02). No difference existed in resting myocardial blood flow between baseline conditions and epidural anesthesia (0.85±0.24 v 1.03±0.27 mL/min/g, respectively). Hyperemia during thoracic epidural anesthesia increased myocardial blood flow to 4.31±1.07 mL/min/g (p = 0.0008 v baseline) and blood volume to 0.17±0.04 mL/mL (p = 0.005 baseline). After sympathetic stimulation, no difference in myocardial blood flow parameters was observed CONCLUSIONS: Acute cardiac sympathectomy by thoracic epidural anesthesia increased the blood volume in the myocardial capillary system. Also, thoracic epidural anesthesia increased hyperemic myocardial blood flow, indicating augmented endothelial-independent vasodilator capacity of the myocardium.

[Acute anterior myocardial infarction after rituximab]. / Akuter Vorderwandinfarkt nach Rituximab.

HISTORY: A 36-year-old man with a history of PR3-ANCA positive granulomatosis with polyangiitis presented with chest pain at the emergency department. Due to his underlying disease, he was treated with Rituximab in regular intervals. The last Rituximab infusion was admitted one day before presentation. INVESTIGATION: The ECG showed marked ST elevation in V1-V4. DIAGNOSIS, TREATMENT AND COURSE: After the diagnosis of an acute anterior myocardial infarction, the patient was prepared for acute percutaneous coronary intervention. During transport to the cardiac catheterization laboratory, he suffered a cardiac arrest due to ventricular fibrillation. After successful resuscitation, the cardiac catheterization showed no evidence of relevant coronary stenosis. Because of suspected coronary spasm of left anterior descending artery the therapy was extended with a calcium channel blocker. A single chamber cardiac defibrillator was implanted for secondary prevention. CONCLUSION: Acute coronary syndrome is a possible side effect of rituximab therapy. The reported case emphasizes a correlation between Rituximab therapy and cardiac event.

Markers for silent atrial fibrillation in esophageal long-term electrocardiography.

PURPOSE: Paroxysmal atrial fibrillation (PAF) often remains undiagnosed. Long-term surface ECG is used for screening, but has limitations. Esophageal ECG (eECG) allows recording high quality atrial signals, which were used to identify markers for PAF. METHODS: In 50 patients (25 patients with PAF; 25 controls) an eECG and surface ECG was recorded simultaneously. Partially A-V blocked atrial runs (PBARs) were quantified, atrial signal duration in eECG was measured. RESULTS: eECG revealed 1.8‰ of atrial premature beats in patients with known PAF to be PBARs with a median duration of 853ms (interquartile range (IQR) 813-1836ms) and a median atrial cycle length of 366ms (IQR 282-432ms). Even during a short recording duration of 2.1h (IQR 1.2-17.2h), PBARs occurred in 20% of PAF patients but not in controls (p=0.05). Left atrial signal duration was predictive for PAF (72% sensitivity, 80% specificity). CONCLUSIONS: eECG reveals partially blocked atrial runs and prolonged left atrial signal duration - two novel surrogate markers for PAF.

A Baseline Wander Tracking System for Artifact Rejection in Long-Term Electrocardiography.

Long-term electrocardiogram (ECG) signals might suffer from relevant baseline disturbances during physical activity. Motion artifacts in particular are more pronounced with dry surface or esophageal electrodes which are dedicated to prolonged ECG recording. In this paper we present a method called baseline wander tracking (BWT) that tracks and rejects strong baseline disturbances and avoids concurrent saturation of the analog front-end. The proposed algorithm shifts the baseline level of the ECG signal to the middle of the dynamic input range. Due to the fast offset shifts, that produce much steeper signal portions than the normal ECG waves, the true ECG signal can be reconstructed offline and filtered using computationally intensive algorithms. Based on Monte Carlo simulations we observed reconstruction errors mainly caused by the non-linearity inaccuracies of the DAC. However, the signal to error ratio of the BWT is higher compared to an analog front-end featuring a dynamic input ranges above 15 mV if a synthetic ECG signal was used. The BWT is additionally able to suppress (electrode) offset potentials without introducing long transients. Due to its structural simplicity, memory efficiency and the DC coupling capability, the BWT is dedicated to high integration required in long-term and low-power ECG recording systems.

[Future cardiac pacemakers ­ technical visions]. / Der Herzschrittmacher der Zukunft - technische Visionen.

Cardiac pacemakers are routinely used for the treatment of bradyarrhythmias. Contemporary pacemakers are reliable and allow for a patient specific programming. However, pacemaker replacements due to battery depletion are common (~25 % of all implantation procedures) and bear the risk of complications. Batteryless pacemakers may allow overcoming this limitation. To power a batteryless pacemaker, a mechanism for intracorporeal energy harvesting is required. Such a generator may consist out of subcutaneously implanted solar cells, transforming the small amount of transcutaneously available light into electrical energy. Alternatively, intravascular turbines may harvest energy from the blood flow. Energy may also be harvested from the ventricular wall motion by a dedicated mechanical clockwork converting motion into electrical energy. All these approaches have successfully been tested in vivo. Pacemaker leads constitute another Achilles heel of contemporary pacemakers. Thus, leadless devices are desired. Miniaturized pacemaker circuits and suitable energy harvesting mechanisms (incorporated in a single device) may allow catheter-based implantation of the pacemaker in the heart. Such miniaturized battery- and leadless pacemakers would combine the advantages of both approaches and overcome major limitations of today's systems.

The first batteryless, solar-powered cardiac pacemaker.

BACKGROUND: Contemporary pacemakers (PMs) are powered by primary batteries with a limited energy-storing capacity. PM replacements because of battery depletion are common and unpleasant and bear the risk of complications. Batteryless PMs that harvest energy inside the body may overcome these limitations. OBJECTIVE: The goal of this study was to develop a batteryless PM powered by a solar module that converts transcutaneous light into electrical energy. METHODS: Ex vivo measurements were performed with solar modules placed under pig skin flaps exposed to different irradiation scenarios (direct sunlight, shade outdoors, and indoors). Subsequently, 2 sunlight-powered PMs featuring a 4.6-cm(2) solar module were implanted in vivo in a pig. One prototype, equipped with an energy buffer, was run in darkness for several weeks to simulate a worst-case scenario. RESULTS: Ex vivo, median output power of the solar module was 1963 µW/cm(2) (interquartile range [IQR] 1940-2107 µW/cm(2)) under direct sunlight exposure outdoors, 206 µW/cm(2) (IQR 194-233 µW/cm(2)) in shade outdoors, and 4 µW/cm(2) (IQR 3.6-4.3 µW/cm(2)) indoors (current PMs use approximately 10-20 µW). Median skin flap thickness was 4.8 mm. In vivo, prolonged SOO pacing was performed even with short irradiation periods. Our PM was able to pace continuously at a rate of 125 bpm (3.7 V at 0.6 ms) for 1½ months in darkness. CONCLUSION: Tomorrow's PMs might be batteryless and powered by sunlight. Because of the good skin penetrance of infrared light, a significant amount of energy can be harvested by a subcutaneous solar module even indoors. The use of an energy buffer allows periods of darkness to be overcome.

Graphics-processor-unit-based parallelization of optimized baseline wander filtering algorithms for long-term electrocardiography.

Long-term electrocardiogram (ECG) often suffers from relevant noise. Baseline wander in particular is pronounced in ECG recordings using dry or esophageal electrodes, which are dedicated for prolonged registration. While analog high-pass filters introduce phase distortions, reliable offline filtering of the baseline wander implies a computational burden that has to be put in relation to the increase in signal-to-baseline ratio (SBR). Here, we present a graphics processor unit (GPU)-based parallelization method to speed up offline baseline wander filter algorithms, namely the wavelet, finite, and infinite impulse response, moving mean, and moving median filter. Individual filter parameters were optimized with respect to the SBR increase based on ECGs from the Physionet database superimposed to autoregressive modeled, real baseline wander. A Monte-Carlo simulation showed that for low input SBR the moving median filter outperforms any other method but negatively affects ECG wave detection. In contrast, the infinite impulse response filter is preferred in case of high input SBR. However, the parallelized wavelet filter is processed 500 and four times faster than these two algorithms on the GPU, respectively, and offers superior baseline wander suppression in low SBR situations. Using a signal segment of 64 mega samples that is filtered as entire unit, wavelet filtering of a seven-day high-resolution ECG is computed within less than 3 s. Taking the high filtering speed into account, the GPU wavelet filter is the most efficient method to remove baseline wander present in long-term ECGs, with which computational burden can be strongly reduced.

Successful pacing using a batteryless sunlight-powered pacemaker.

AIMS: Today's cardiac pacemakers are powered by batteries with limited energy capacity. As the battery's lifetime ends, the pacemaker needs to be replaced. This surgical re-intervention is costly and bears the risk of complications. Thus, a pacemaker without primary batteries is desirable. The goal of this study was to test whether transcutaneous solar light could power a pacemaker. METHODS AND RESULTS: We used a three-step approach to investigate the feasibility of sunlight-powered cardiac pacing. First, the harvestable power was estimated. Theoretically, a subcutaneously implanted 1 cm(2) solar module may harvest ∼2500 µW from sunlight (3 mm implantation depth). Secondly, ex vivo measurements were performed with solar cells placed under pig skin flaps exposed to a solar simulator and real sunlight. Ex vivo measurements under real sunlight resulted in a median output power of 4941 µW/cm(2) [interquartile range (IQR) 3767-5598 µW/cm(2), median skin flap thickness 3.0 mm (IQR 2.7-3.3 mm)]. The output power strongly depended on implantation depth (ρSpearman = -0.86, P < 0.001). Finally, a batteryless single-chamber pacemaker powered by a 3.24 cm(2) solar module was implanted in vivo in a pig to measure output power and to pace. In vivo measurements showed a median output power of >3500 µW/cm(2) (skin flap thickness 2.8-3.84 mm). Successful batteryless VVI pacing using a subcutaneously implanted solar module was performed. CONCLUSION: Based on our results, we estimate that a few minutes of direct sunlight (irradiating an implanted solar module) allow powering a pacemaker for 24 h using a suitable energy storage. Thus, powering a pacemaker by sunlight is feasible and may be an alternative energy supply for tomorrow's pacemakers.

Performance analysis of a miniature turbine generator for intracorporeal energy harvesting.

Replacement intervals of implantable medical devices are commonly dictated by battery life. Therefore, intracorporeal energy harvesting has the potential to reduce the number of surgical interventions by extending the life cycle of active devices. Given the accumulated experience with intravascular devices such as stents, heart valves, and cardiac assist devices, the idea to harvest a small fraction of the hydraulic energy available in the cardiovascular circulation is revisited. The aim of this article is to explore the technical feasibility of harvesting 1 mW electric power using a miniature hydrodynamic turbine powered by about 1% of the cardiac output flow in a peripheral artery. To this end, numerical modelling of the fluid mechanics and experimental verification of the overall performance of a 1:1 scale friction turbine are performed in vitro. The numerical flow model is validated for a range of turbine configurations and flow conditions (up to 250 mL/min) in terms of hydromechanic efficiency; up to 15% could be achieved with the nonoptimized configurations of the study. Although this article does not entail the clinical feasibility of intravascular turbines in terms of hemocompatibility and impact on the circulatory system, the numerical model does provide first estimates of the mechanical shear forces relevant to blood trauma and platelet activation. It is concluded that the time-integrated shear stress exposure is significantly lower than in cardiac assist devices due to lower flow velocities and predominantly laminar flow.