Project description:Human cardiac myocytes derived from pluripotent stem cells (hCM) have invigorated interest in genetic disease mechanisms and cardiac safety testing; however, the technology to fully assess electrophysiological function in an assay that is amenable to high throughput screening has lagged. We describe a fully contactless system using optical pacing with an infrared (IR) laser and multi-site high fidelity fluorescence imaging to assess multiple electrophysiological parameters from hCM monolayers in a standard 96-well plate. Simultaneous multi-site action potentials (FluoVolt) or Ca2+ transients (Fluo4-AM) were measured, from which high resolution maps of conduction velocity and action potential duration (APD) were obtained in a single well. Energy thresholds for optical pacing were determined for cell plating density, laser spot size, pulse width, and wavelength and found to be within ranges reported previously for reliable pacing. Action potentials measured using FluoVolt and a microelectrode exhibited the same morphology and rate of depolarization. Importantly, we show that this can be achieved accurately with minimal damage to hCM due to optical pacing or fluorescence excitation. Finally, using this assay we demonstrate that hCM exhibit reproducible changes in repolarization and impulse conduction velocity for Flecainide and Quinidine, two well described reference compounds. In conclusion, we demonstrate a high fidelity electrophysiological screening assay that incorporates optical pacing with IR light to control beating rate of hCM monolayers.
Project description:The aim of this survey, which was open to all Italian cardiologists involved in arrhythmia, was to assess common practice regarding sedation and analgesia in interventional electrophysiology procedures in Italy. The survey consisted of 28 questions regarding the approach to sedation used for elective direct-current cardioversion (DCC), subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation, atrial fibrillation (AF) ablation, ventricular tachycardia (VT) ablation, and transvenous lead extraction procedures. A total of 105 cardiologists from 92 Italian centres took part in the survey. The rate of centres where DCC, S-ICD implantation, AF ablation, VT ablation and lead extraction procedures were performed without anaesthesiologic assistance was 60.9%, 23.6%, 51.2%, 37.3%, and 66.7%, respectively. When these procedures were performed without anaesthesiologic assistance, the drugs (in addition to local anaesthetics) commonly administered were benzodiazepines (from 64.3% to 79.6%), opioids (from 74.4% to 88.1%), and general anaesthetics (from 7.1% to 30.4%). Twenty-three (21.9%) of the 105 cardiologists declared that they routinely administered propofol, without the supervision of an anaesthesiologist, in at least one of the above-mentioned procedures. In current Italian clinical practice, there is a lack of uniformity in the sedation/analgesia approach used in interventional electrophysiology procedures.
Project description:Cardiac implantable electronic device (CIED) implants and electrophysiological procedures share a common step: vascular access. On behalf of the AIAC Ricerca Investigators' Network, we conducted a survey to outline Italian common practice regarding vascular access in EP-lab. All Italian physicians with experience in CIED implantation and electrophysiology were invited to answer an online questionnaire (from May 2020 to November 2020) featuring 20 questions. In total, 103 cardiologists (from 92 Italian hospitals) answered the survey. Vascular access during CIED implants was considered the most complex step following lead placement by 54 (52.4%) respondents and the most complex for 35 (33.9%). In total, 54 (52.4%) and 49 (47.6%) respondents considered the cephalic and subclavian vein the first option, respectively (intrathoracic and extrathoracic subclavian/axillary vein by 22 and 27, respectively). In total, 45 (43.7%) respondents performed close arterial femoral accesses manually; only 12 (11.7%) respondents made extensive use of vascular closure devices. A total of 46 out of 103 respondents had experience in ultrasound-guided vascular accesses, but only 10 (22%) used it for more than 50% of the accesses. In total, 81 (78.6%) respondents wanted to increase their ultrasound-guided vascular access skills. Reducing complications is a goal to reach in cardiac stimulation and electrophysiological procedures. Our survey shows the heterogeneity of the vascular approaches used in Italian centres. Some vascular accesses were proved to be superior to others in terms of complications, with ultrasound-guided puncture as an emerging technique. More effort to produce the standardization of vascular accesses could be made by scientific societies.
Project description:BackgroundThe electric response of myocardial tissue to periodic field stimuli has attracted significant attention as the basis for low-energy antifibrillation pacing, potentially more effective than traditional single high-energy shocks. In conventional models, an electric field produces a highly nonuniform response of the myocardial wall, with discrete excitations, or hot spots (HS), occurring at cathodal tissue surfaces or large coronary vessels. We test this prediction using novel 3-dimensional tomographic optical imaging.Methods and resultsExperiments were performed in isolated coronary perfused pig ventricular wall preparations stained with near-infrared voltage-sensitive fluorescent dye DI-4-ANBDQBS. The 3-dimensional coordinates of HS were determined using alternating transillumination. To relate HS formation with myocardial structures, we used ultradeep confocal imaging (interrogation depths, >4 mm). The peak HS distribution is located deep inside the heart wall, and the depth is not significantly affected by field polarity. We did not observe the strong colocalization of HS with major coronary vessels anticipated from theory. Yet, we observed considerable lateral displacement of HS with field polarity reversal. Models that de-emphasized lateral intracellular coupling and accounted for resistive heterogeneity in the extracellular space showed similar HS distributions to the experimental observations.ConclusionsThe HS distributions within the myocardial wall and the significant lateral displacements with field polarity reversal are inconsistent with standard theories of defibrillation. Extended theories based on enhanced descriptions of cellular scale electric mechanisms may be necessary. The considerable lateral displacement of HS with field polarity reversal supports the hypothesis of biphasic stimuli in low-energy antifibrillation pacing being advantageous.
Project description:Initial efforts to artificially stimulate the heart were borne out of a necessity to prevent catastrophic bradycardic events. The initial pacemaker systems were large, bulky external devices. However, advancements in technology allowed for the development of internally powered, fully implantable devices. Further advancements resulted in more complex, programmable devices, but the overall systems have remained largely unchanged for more than 50 years. The most recent advancements in the field have represented fundamental paradigm shifts in both pacemaker design and the approach to cardiac pacing. These efforts have focused on reducing and eliminating hardware to reduce the risk of complications and to focus on improving cardiac efficiency to improve clinical outcomes. In this article, the authors explore these advances including leadless pacemaker systems, permanent His bundle pacing and advances in the field of cardiac resynchronisation therapy.
Project description:The traditional cardiac model-building paradigm involves constructing a composite model using data collected from many cells. Equations are derived for each relevant cellular component (e.g., ion channel, exchanger) independently. After the equations for all components are combined to form the composite model, a subset of parameters is tuned, often arbitrarily and by hand, until the model output matches a target objective, such as an action potential. Unfortunately, such models often fail to accurately simulate behavior that is dynamically dissimilar (e.g., arrhythmia) to the simple target objective to which the model was fit. In this study, we develop a new approach in which data are collected via a series of complex electrophysiology protocols from single cardiac myocytes and then used to tune model parameters via a parallel fitting method known as a genetic algorithm (GA). The dynamical complexity of the electrophysiological data, which can only be fit by an automated method such as a GA, leads to more accurately parameterized models that can simulate rich cardiac dynamics. The feasibility of the method is first validated computationally, after which it is used to develop models of isolated guinea pig ventricular myocytes that simulate the electrophysiological dynamics significantly better than does a standard guinea pig model. In addition to improving model fidelity generally, this approach can be used to generate a cell-specific model. By so doing, the approach may be useful in applications ranging from studying the implications of cell-to-cell variability to the prediction of intersubject differences in response to pharmacological treatment.
Project description:COVID-19 outbreak had a major impact on the organization of care in Italy, and a survey to evaluate provision of for arrhythmia during COVID-19 outbreak (March-April 2020) was launched. A total of 104 physicians from 84 Italian arrhythmia centres took part in the survey. The vast majority of participating centres (95.2%) reported a significant reduction in the number of elective pacemaker implantations during the outbreak period compared to the corresponding two months of year 2019 (50.0% of centres reported a reduction of > 50%). Similarly, 92.9% of participating centres reported a significant reduction in the number of implantable cardioverter-defibrillator (ICD) implantations for primary prevention, and 72.6% a significant reduction of ICD implantations for secondary prevention (> 50% in 65.5 and 44.0% of the centres, respectively). The majority of participating centres (77.4%) reported a significant reduction in the number of elective ablations (> 50% in 65.5% of the centres). Also the interventional procedures performed in an emergency setting, as well as acute management of atrial fibrillation had a marked reduction, thus leading to the conclusion that the impact of COVID-19 was disrupting the entire organization of health care, with a massive impact on the activities and procedures related to arrhythmia management in Italy.
Project description:Since the introduction of transvenous cardiac pacing leads, pacemaker system design has remained similar for several decades. Progressive miniaturisation of electronic circuitry and batteries has enabled a smaller, single pacing unit comprising the intracardiac electrodes, generator and computer. This review explores the development of leadless pacing, the clinical trials comparing leadless to transvenous pacing in addition to the future developments of multi-chamber leadless pacing.