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Cardiac arrhythmias are a leading cause of morbidity and mortality in the developed world, estimated to be responsible for hundreds of thousands of deaths annually. Our understanding of the electrophysiological mechanisms of such arrhythmias has grown since they were formally characterized in the late nineteenth century, and this has led to the development of numerous devices and therapies that have markedly improved outcomes for patients affected by such conditions. Despite these advancements, the application of a single large shock remains the clinical standard for treating deadly tachyarrhythmias. Such defibrillating shocks are undoubtedly effective in terminating such arrhythmias; however, they are applied without forewarning, contributing to the patient’s stress and anxiety; they can be intensely painful; and they can have adverse psychological and physiological effects on patients. In recent years, there has been interest in developing defibrillation protocols that can terminate arrhythmias without crossing the human pain threshold for energy delivery, generally estimated to be between 0.1 and 1 J. In this article, we review existing literature on the development of such low-energy defibrillation methods and their underlying mechanisms, in an attempt to broadly describe the current landscape of these technologies.

BACKGROUND Pericardial access is complicated by two difficulties: confirming when the needle tip is in the pericardial space, and avoiding complications during access, such as inadvertently puncturing other organs. Conventional imaging tools are inadequate for addressing these difficulties, as they lack soft-tissue markers that could be used as guidance during access. A system that can both confirm access and avoid inadvertent organ injury is needed. METHODS A 21G micropuncture needle was modified to include two small electrodes at the needle tip. With continuous bioimpedance monitoring from the electrodes, the needle was used to access the pericardium in porcine models (n = 4). The needle was also visualized in vivo by using an electroanatomical map (n = 2). Bioimpedance data from different tissues were analyzed retrospectively. RESULTS Bioimpedance data collected from the subcutaneous space (992.8 ± 13.1 Ω), anterior mediastinum (972.2 ± 14.2 Ω), pericardial space (323.2 ± 17.1 Ω), mid-myocardium (349.7 ± 87.6 Ω), right ventricular cavity (235.0 ± 9.7 Ω), lung (1142.0 ± 172.0 Ω), liver (575.0 ± 52.6 Ω), and blood (177.5 ± 1.9 Ω) differed significantly by tissue type (P

About 30% of patients with impaired cardiac function have ventricular dyssynchrony and seek cardiac resynchronization therapy (CRT). In this study, we demonstrate synchronized biventricular (BiV) pacing in a leadless fashion by implementing miniaturized and wirelessly powered pacemakers. With their flexible form factors, two pacemakers were implanted epicardially on the right and left ventricles of a porcine model and were inductively powered at 13.56 MHz and 40.68 MHz industrial, scientific, and medical (ISM) bands, respectively. The power consumption of these pacemakers is reduced to µW-level by a novel integrated circuit design, which considerably extends the maximum operating distance. Leadless BiV pacing is demonstrated for the first time in both open-chest and closed-chest porcine settings. The clinical outcomes associated with different interventricular delays are verified through electrophysiologic and hemodynamic responses. The closed-chest pacing only requires the external source power of 0.3 W and 0.8 W at 13.56 MHz and 40.68 MHz, respectively, which leads to specific absorption rates (SARs) 2–3 orders of magnitude lower than the safety regulation limit. This work serves as a basis for future wirelessly powered leadless pacemakers that address various cardiac resynchronization challenges.

Re-entrant arrhythmias—the leading cause of sudden cardiac death—are caused by diseased myocardial tissue and consequent delayed myocardial conduction. Access to the coronary veins that cross the “culprit” scar regions where re-entry originates can provide improved pacing to these delayed regions, offering a novel opportunity to prevent ventricular arrhythmias and circumvent the need for painful defibrillation, risky cardiac ablation, or toxic and often ineffective antiarrhythmic medications. However, there are no pacing electrodes which are small or focal enough to navigate these tributaries. To address this need, we have developed an injectable conductive hydrogel that can fill the epicardial coronary veins and their mid-myocardial tributaries. When connected to a standard pacing lead, these injected hydrogels can be converted into flexible electrodes that directly pace the previously inaccessible mid-myocardial tissue. In our two-component system, hydrogel precursor solutions can be injected through a dual lumen catheter in a minimally invasive deployment strategy to provide direct access to the diseased regions with precision and ease. Mixing of the two solutions upon injection into the vein activates redox-initiated crosslinking of the gel for rapidin situcure without an external stimulus. Anex vivoporcine model was used to identify the requisite viscosity and cure rate for gel retention and homogeneity. Ionic species added to the hydrogel precursor solutions conferred conductivity above target myocardium values that was retained after implantation. Successfulin vivodeployment demonstrated that the hydrogel electrode filled the anterior interventricular vein with extension into the septal (mid-myocardial) venous tributaries to depths far more distal and refined than any current technologies allow. In addition to successful capture and pacing of the heart, analysis of surface ECG tracings revealed a novel pacing observation highly specific for and suggestive of capture of extensive swaths of septal myocardial tissue. This is the first report of an injectable electrode used to successfully pace the mid-myocardium and mimic physiologic conduction. Furthermore,in vivocardiac electroanatomical mapping studies in an ablation scar model showed uniform capture along the hydrogel in the vessels as well as increased capture area compared to point pacing. Collectively, these findings demonstrate that this injectable hydrogel electrode can be deployed to scarred regions of the heart to provide a reliable pacing modality that most closely resembles native conduction with the potential to eliminate delayed myocardial conduction and associated re-entry.One Sentence SummaryInjectable hydrogel electrodes achieve pacing that mimics physiologic conduction by capturing midmyocardial tissue

We propose a novel convolutional neural network framework for mapping a multivariate input to a multivariate output. In particular, we implement our algorithm within the scope of 12-lead surface electrocardiogram (ECG) reconstruction from intracardiac electrograms (EGM) and vice versa. The goal of performing this task is to allow for improved point-of-care monitoring of patients with an implanted device to treat cardiac pathologies. We will achieve this goal with 12-lead ECG reconstruction and by providing a new diagnostic tool for classifying five different ECG types. The algorithm is evaluated on a dataset retroactively collected from 14 patients. Correlation coefficients calculated between the reconstructed and the actual ECG show that the proposed convolutional neural network model represents an efficient, accurate, and superior way to synthesize a 12-lead ECG when compared to previous methods. We can also achieve the same reconstruction accuracy with only one EGM lead as input. We also tested the model in a non-patient specific way and saw a reasonable correlation coefficient. The model was also executed in the reverse direction to produce EGM signals from a 12-lead ECG and found that the correlation was comparable to the forward direction. Lastly, we analyzed the features learned in the model and determined that the model learns an overcomplete basis of our 12-lead ECG space. We then use this basis of features to create a new diagnostic tool for classifying different ECG arrhythmia's on the MIT-BIH arrhythmia database with an average accuracy of 0.98.

Ethanol solubilizes cell membranes, making it useful for various ablation applications. We examined the effect of time and alcohol type on the extent of ablation, quantified as Euclidean distances between color coordinates. We obtained biopsy punch samples (diameter, 6 mm) of left atrial appendage, atrial, ventricular, and septal tissue from porcine hearts and placed them in transwell plates filled with ethanol or methanol for 10, 20, 30, 40, 50, or 60 min. Control samples were taken for each time point. At each time point, samples were collected, cut transversely, and photographed. With use of a custom MATLAB program, all images were analyzed in the CIELAB color space, which is more perceptually uniform than the red-green-blue color space. Euclidean distances were calculated from CIELAB coordinates. The mean and standard error of these distances were analyzed. Two-way analysis of variance was used to test for differences among time points, and 2-tailed t tests, for differences between the alcohol datasets at each time point. Generally, Euclidean distances differed significantly between all time points, except for those immediately adjacent, and methanol produced larger Euclidean distances than ethanol did. Some tissue showed a plateauing effect, potentially indicating transmurality. Mean Euclidean distances effectively indexed alcohol ablation in cardiac tissue. Furthermore, we found that methanol ablated tissue more effectively than ethanol did. With ethanol, the extent of ablation for atrial tissue was largest at 60 min. We conclude that to achieve full transmurality in clinical applications, ethanol must remain in contact with atrial tissue for at least one hour.

INTRODUCTION Few studies have examined heat transfer and thermal injury on the epiesophageal surface during radiofrequency application, or compared the risk of esophageal thermal injury between standard and high-power, short-duration (HPSD) ablation. We studied the thermodynamics of HPSD and standard ablation at different tissue interfaces between the left atrium and esophagus, focusing on epiesophageal temperature changes and thermal injury. METHODS AND RESULTS Fresh porcine heart and esophageal sections were secured to a custom holder and submerged in a temperature-controlled, circulating water bath. During ablation, thermistors recorded temperatures at the catheter tip-atrial interface, epiesophageal-atrial interface, and esophageal lumen. Samples were ablated in triplicate with the following parameters: contact force (15/25g), power (10/20/30 W standard; 40/45/50 W HPSD), and duration (10/20/30 s standard; 5/10/15 s HPSD). Epiesophageal and endoluminal temperature rises were greater in HPSD than in standard ablation (epiesophageal: 5.9 ± 5.6 vs. 2.2 ± 2.0°C, p

Sustained biomaterial thromboresistance has long been a goal and challenge in blood-contacting device design. Endothelialization is one of the most successful strategies to achieve long-term thromboresistance of blood-contacting devices, with the endothelial cell layer providing dynamic hemostatic regulation. It is well established that endothelial cell behavior is influenced by interactions with the underlying extracellular matrix (ECM). Numerous researchers have sought to exploit these interactions to generate improved blood-contacting devices by investigating the expression of hemostatic regulators in endothelial cells on various ECM coatings. The ability to select substrates that promote endothelial cell-mediated thromboresistance is crucial to advancing material design strategies to improve cardiovascular device outcomes. This review provides an overview of endothelial cell regulation of hemostasis, the major components found within the cardiovascular basal lamina, and the interactions of endothelial cells with prominent ECM components of the basement membrane. A summary of ECM-mimetic strategies used in cardiovascular devices is provided with a focus on the effects of key adhesion modalities on endothelial cell regulators of hemostasis.

There is a growing clinical need to address high failure rates of small diameter (

Author(s): Lyu, Hongming; John, Mathews; Burkland, David; Greet, Brian; Post, Allison; Babakhani, Aydin; Razavi, Mehdi | Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

More than 370,000 Americans die every year from coronary artery disease (CAD). Early detection and treatment are crucial to reducing this number. Current diagnostic and disease-monitoring methods are invasive, costly, and time-consuming. Using an electronic stethoscope and spectral and nonlinear dynamics analysis of the recorded heart sound, we investigated the acoustic signature of CAD in subjects with only a single coronary occlusion before and after stent placement, as well as subjects with clinically normal coronary arteries. The CAD signature was evaluated by estimating power ratios of the total power above 150 Hz over the total power below 150 Hz of the FFT of the acoustic signal. Additionally, approximate entropy values were estimated to assess the differences induced by the stent placement procedure to the acoustic signature of the signals in the time domain. The groups were identified with this method with 82% sensitivity and 64% specificity (using the power ratio method) and 82% sensitivity and 55% specificity (using the approximate entropy). Power ratios and approximate entropy values after stent placement are not statistically different from those estimated from subjects with no coronary occlusions. Our approach demonstrates that the effect of stent placement on coronary occlusions can be monitored using an electronic stethoscope.

At birth, the mechanical environment of valves changes radically as fetal shunts close and pulmonary and systemic vascular resistances change. Given that valves are reported to be mechanosensitive, we investigated remodeling induced by perinatal changes by examining compositional and structural differences of aortic and mitral valves (AVs, MVs) between 2-day-old and 3rd fetal trimester porcine valves using immunohistochemistry and Movat pentachrome staining. Aortic valve composition changed more with birth than the MV, consistent with a greater change in AV hemodynamics. At 2 days, AV demonstrated a trend of greater versican and elastin ( P = 0.055), as well as greater hyaluronan turnover (hyaluronan receptor for endocytosis, P = 0.049) compared with the 3rd-trimester samples. The AVs also demonstrated decreases in proteins related to collagen synthesis and fibrillogenesis with birth, including procollagen I, prolyl 4-hydroxylase, biglycan (all P ≤ 0.005), and decorin ( P = 0.059, trend). Both AVs and MVs demonstrated greater delineation between the leaflet layers in 2-day-old compared with 3rd-trimester samples, and AVs demonstrated greater saffron-staining collagen intensity, suggesting more mature collagen in 2-day-old compared with 3rd-trimester samples (each P < 0.05). The proportion of saffron-staining collagen also increased in AV with birth ( P < 0.05). The compositional and structural changes that occur with birth, as noted in this study, likely are important to proper neonatal valve function. Furthermore, normal perinatal changes in hemodynamics often do not occur in congenital valve disease; the corresponding perinatal matrix maturation may also be lacking and could contribute to poor function of congenitally malformed valves.

Objective— Although valvular endothelial cells have unique responses compared with vascular endothelial cells, valvular regulation of hemostasis is not well-understood. Heart valves remodel throughout a person’s lifetime, resulting in changes in extracellular matrix composition and tissue mechanical properties that may affect valvular endothelial cell hemostatic function. This work assessed valvular endothelial cell regulation of hemostasis in situ and in vitro as a function of specimen age. Approach and Results— Porcine aortic valves were assigned to 1 of 3 age groups: Young (YNG) (6 weeks); Adult (ADT) (6 months); or Elderly (OLD) (2 years). Histological examination of valves showed that secreted thrombotic/antithrombotic proteins localize at the valve endothelium and tissue interior. Gene expression and immunostains for von Willebrand factor (VWF), tissue factor pathway inhibitor, and tissue plasminogen activator in YNG porcine aortic valve endothelial cells were higher than they were for OLD, whereas plasminogen activator inhibitor 1 levels in OLD were higher than those for YNG and ADT. Histamine-stimulated YNG porcine aortic valve endothelial cells released higher concentrations of VWF proteins than OLD, and the fractions of VWF-140 fragments was not different between age groups. A calcific aortic valve disease in vitro model using valvular interstitial cells confirmed that VWF in culture significantly increased valvular interstitial cell nodule formation and calcification. Conclusions— Hemostatic protein regulation in aortic valve tissues and in valvular endothelial cells changes with age. The presence of VWF and other potential hemostatic proteins increase valvular interstitial cell calcification in vitro. Therefore, the increased capacity of elderly valves to sequester the hemostatic proteins, together with age-associated loss of extracellular matrix organization, warrants investigation into potential role of these proteins in the formation of calcific nodules.

Rice Helping Hands (RHH) is tasked with designing and developing a wrist rehabilitation device for pediatric patients with spastic cerebral palsy (CP).Copyright © 2012 by ASME