High-energy Shock Research Articles

The use of high-energy shock wave treatment as pre-activation of sintering high-entropy solid solutions of transition metal borides and carbides

Synthesis of solid solutions of transition metal borides (NbB2, TaB2, HfB2 and ZrB2) and carbides (NbC, TaC, HfC, ZrC and VC) was carried out via sintering the individual components without applying pressure. To activate the interaction of the components, the initial powders were processed by high-energy shock wave treatment (HESWT). HESWT enables the formation of homogeneous solid solution for a mixture of carbides; however, this method did not give the desired results for a mixture of transition metal borides, likely due to the higher strength of borides crystal lattice in comparison with carbides.

Personalizing configuration for atrial fibrillation external electrical cardioversion to improve first shock efficacy

Despite the common use of biphasic electrical cardioversion (ECV) to convert atrial fibrillation (AF), we lack definite recommendations on electrode configuration. We adopted a quasi-experimental design enrolling all candidates to ECV for AF. In the first stage, two units were involved, one using antero-apical pads (AAP) and the second antero-posterior adhesive patches (APP). These data enabled the creation of a decision algorithm to personalize the ECV approach, which was subsequently validated during the second stage. A total of 492 patients were enrolled overall. In the first stage, APP and AAP presented similar conversion rates (87.4 vs. 86.9% at first attempt of a step-up protocol, P = 0.661). While body surface area (BSA) ≤2.12 m2 was an independent predictor in the overall population, the two components (height and weight) acted differently in the two configurations: being height ≤1.73 m2 a significant cut-off value in the AAP subgroup, and weight <83 kg in the APP subgroup. Considering these cut-offs, we developed a decision algorithm for electrode configuration. In the second stage, algorithm validation confirmed an improvement in the first shock efficacy with respect to the results of the first stage (93.2 vs. 87.2%, P = 0.025), with a significant reduction in shock impedance (70.8 ± 15.3 vs. 81.8 ± 15.6, P < 0.001). Patients with high BSA require high energy shocks for sinus rhythm restoration with ECV. Weight seems to affect more APP configuration, while height seems to impact more for the AAP. These findings have the potential to optimize ECV in clinical practice.

Non-monotonous dose response function of the termination of spiral wave chaos

The conventional termination technique of life threatening cardiac arrhythmia like ventricular fibrillation is the application of a high-energy electrical defibrillation shock, coming along with severe side-effects. In order to improve the current treatment reducing these side-effects, the application of pulse sequences of lower energy instead of a single high-energy pulse are promising candidates. In this study, we show that in numerical simulations the dose-response function of pulse sequences applied to two-dimensional spiral wave chaos is not necessarily monotonously increasing, but exhibits a non-trivial frequency dependence. This insight into crucial phenomena appearing during termination attempts provides a deeper understanding of the governing termination mechanisms in general, and therefore may open up the path towards an efficient termination of cardiac arrhythmia in the future.

The ultrafast pixel array camera system and its applications in high energy density physics.

Diagnostics in high energy density physics, shock physics, and related fields are primarily driven by a need to record rapidly time-evolving signals in single-shot events. These measurements are often limited by channel count and signal degradation issues on cable links between the detector and digitizer. We present the Ultrafast Pixel Array Camera (UPAC), a compact and flexible detector readout system with 32 waveform-recording channels at up to 10 Gsample/s and 1.8GHz analog bandwidth. The compact footprint allows the UPAC to be directly embedded in the detector environment. A key enabling technology is the PSEC4A chip, an eight-channel switch-capacitor array sampling device with up to 1056 samples/channel. The UPAC system includes a high-density input connector that can plug directly into an application-specific detector board, programmable control, and serial readout, with less than 5W of power consumption in full operation. We present the UPAC design and characterization, including a measured timing resolution of ∼20ps or better on acquisitions of sub-nanosecond pulses with minimal system calibrations. Example applications of the UPAC are also shown to demonstrate operation of a solid-state streak camera, an ultrafast imaging array, and a neutron time-of-flight spectrometer.

PO-678-03 ANTITACHYCARDIA PACING AT THE HIS BUNDLE IS SAFER THAN TRADITIONAL RIGHT VENTRICULAR ANTITACHYCARDIA PACING IN A CANINE MYOCARDIAL INFARCTION MODEL

Antitachycardia pacing (ATP) therapy delivers low-energy pacing to the right ventricle (RV) to terminate episodes of ventricular tachycardia (VT). While this treatment has reduced instances of high-energy shocks in patients, some episodes of VT are less responsive to ATP, and adverse events, such as VT acceleration and degeneration into VF, remain a concern. Improving the success rate and safety of ATP is therefore desirable.

Critical point and supercritical regime of MgO

The position of the critical point determines the top of the liquid-vapor coexistence dome, and it is a physical parameter of fundamental importance in the study of high-energy shocks, including those associated with large planetary impacts. For most major planetary materials, such as oxides and silicates, the estimated position of the critical point is below $1\phantom{\rule{4pt}{0ex}}\mathrm{g}/{\mathrm{cm}}^{3}$ at temperatures above 5000 K. Here we compute the position of the critical point of one of the most ubiquitous materials: MgO. For this we perform first-principles molecular dynamics simulations. We find the critical density to be in the 0.45--$0.6\phantom{\rule{4pt}{0ex}}\mathrm{g}/{\mathrm{cm}}^{3}$ range and the critical temperature in the 6500--7000 K range. We investigate in detail the behavior of MgO in the subcritical and supercritical regimes, and we provide insight into the structure and chemical speciation. We see a change in Mg-O speciation toward lower degrees of coordination as the temperature is increased from 4000 to 10 000 K. This change in speciation is less pronounced at higher densities. We observe the liquid-gas separation in nucleating nanobubbles at densities below the liquid spinodal. The majority of the chemical species forming the incipient gas phase consists of isolated Mg and O atoms and some MgO and ${\mathrm{O}}_{2}$ molecules. We find that the ionization state of the atoms in the liquid phase is close to the nominal charge, but it almost vanishes close to the liquid-gas boundary and in the gas phase, which is consequently largely atomic.

Computational Model for Therapy Optimization of Wearable Cardioverter Defibrillator: Shockable Rhythm Detection and Optimal Electrotherapy.

Wearable cardioverter defibrillator (WCD) is a life saving, wearable, noninvasive therapeutic device that prevents fatal ventricular arrhythmic propagation that leads to sudden cardiac death (SCD). WCD are frequently prescribed to patients deemed to be at high arrhythmic risk but the underlying pathology is potentially reversible or to those who are awaiting an implantable cardioverter-defibrillator. WCD is programmed to detect appropriate arrhythmic events and generate high energy shock capable of depolarizing the myocardium and thus re-initiating the sinus rhythm. WCD guidelines dictate very high reliability and accuracy to deliver timely and optimal therapy. Computational model-based process validation can verify device performance and benchmark the device setting to suit personalized requirements. In this article, we present a computational pipeline for WCD validation, both in terms of shock classification and shock optimization. For classification, we propose a convolutional neural network-“Long Short Term Memory network (LSTM) full form” (Convolutional neural network- Long short term memory network (CNN-LSTM)) based deep neural architecture for classifying shockable rhythms like Ventricular Fibrillation (VF), Ventricular Tachycardia (VT) vs. other kinds of non-shockable rhythms. The proposed architecture has been evaluated on two open access ECG databases and the classification accuracy achieved is in adherence to American Heart Association standards for WCD. The computational model developed to study optimal electrotherapy response is an in-silico cardiac model integrating cardiac hemodynamics functionality and a 3D volume conductor model encompassing biophysical simulation to compute the effect of shock voltage on myocardial potential distribution. Defibrillation efficacy is simulated for different shocking electrode configurations to assess the best defibrillator outcome with minimal myocardial damage. While the biophysical simulation provides the field distribution through Finite Element Modeling during defibrillation, the hemodynamic module captures the changes in left ventricle functionality during an arrhythmic event. The developed computational model, apart from acting as a device validation test-bed, can also be used for the design and development of personalized WCD vests depending on subject-specific anatomy and pathology.

Abstract 12651: Non-Pharmacological Interventions to Improve Electrical Cardioversion Success in Patients With Atrial Fibrillation: A Scoping Review

Introduction: Electrical cardioversion is used commonly in patients with atrial fibrillation (AF). However, success rates vary and practical guidance is limited. Methods: We searched CENTRAL, Medline and EMBASE from inception to present and the grey literature. We included randomized controlled trials (RCTs) comparing any two interventions. Outcomes were initial and cumulative cardioversion success. We pooled data using random effects models. Results: From 13481 citations, we included 52 RCTs. Biphasic as compared to monophasic waveforms resulted in a higher rate of cardioversion for initial (18 studies, risk ratio [RR] 1.45, 95% confidence interval [CI] 1.10-1.90, I 2 =89%) and cumulative success (21 studies, RR 1.07, 95% CI 1.02-1.13, I 2 =75%). Fixed, maximum-energy shocks as compared to low-dose escalating energy protocols had a higher likelihood of initial (4 studies, RR 1.62, 95% CI 1.33-1.98, I 2 =72%) but not cumulative success (3 studies, RR 1.13, 95% CI 0.97-1.32, I 2 =86%). Initial or cumulative cardioversion success did not differ significantly for several other interventions. This included: antero-apical/lateral vs. anteroposterior positioned pads (initial: 10 studies, RR 1.06, 95% CI 0.89-1.27; cumulative: 13 studies, RR 0.99, 95% CI 0.95-1.04); rectilinear/pulsed biphasic vs. biphasic truncated exponential waveform (initial: 3 studies, RR 1.07, 95% CI 0.76-1.50; cumulative: 3 studies, RR 0.95, 95% CI 0.80-1.12); cathodal vs. anodal configuration (cumulative: 2 studies, RR 1.03, 95% CI 0.97-1.09); magnesium pre-treatment vs. none (initial: 2 studies, RR 1.36, 95% CI 0.82-2.24; cumulative: 2 studies, RR 1.05, 95% CI 0.96-1.14); and patches vs. manual pressure/paddles (initial: 2 studies, RR 1.04, 95% CI 0.26-4.12; cumulative: 2 studies, RR 0.87, 95% CI 0.61-1.25). Conclusions: Biphasic shock waveforms and high-energy shocks increase the efficacy of cardioversion of AF. Other interventions, including pad placement, biphasic waveform properties, electrode polarity, electrolyte pre-treatment, and manual pressure require further study.

Smart Shockwave Responsive Titania-Based Nanoparticles for Cancer Treatment.

Nanomedicine is an emerging treatment approach for many cancers, characterized by having high sensitivity and selectivity for tumor cells and minimal toxic effects induced by the conventional chemotherapeutics. In these context, smart nanoparticles (NPs) are getting increasingly relevant in the development of new therapies. NPs with specific chemical composition and/or structure and being stimuli-responsive to magnetic, light or ultrasound waves are new promising tools. In the present work, amorphous-titania propyl-amine functionalized (a-TiO2-NH2) NPs, coated with bovine serum albumin (BSA), are stimulated with high energy shock waves to induce cytotoxic effects in cancer cells. First, a new method to coat a-TiO2-NH2 NPs with BSA (a-TiO2-NH2/BSA) was proposed, allowing for a high dispersion and colloidal stability in a cell culture media. The a-TiO2-NH2/BSA NPs showed no cancer cell cytotoxicity. In a second step, the use of shock waves to stimulate a-TiO2-NH2/BSA NPs, was evaluated and optimized. A systematic study was performed in in vitro cell culture aiming to impair the cancer cell viability: NP concentrations, time steps and single versus multiple shock waves treatments were studied. The obtained results highlighted the relevance of NPs design and administration time point with respect to the shock wave treatment and allow to hypothesize mechanical damages to cells.

Implantable vagus nerve stimulation system performance is not affected by internal or external defibrillation shocks

PurposeAutonomic regulation therapy (ART) for heart failure (HF) is delivered using vagus nerve stimulation (VNS), and has been associated with improvement in cardiac function and HF symptoms. VNS is delivered using an implantable pulse generator (IPG) and a lead placed around the cervical vagus nerve. Because HF patients may receive concomitant cardiac defibrillation therapy, testing was conducted to determine the effect of defibrillation (DF) on VNS system performance.MethodsNormal swine (n = 4) with VNS system implants on the right cervical vagus nerve received sequential defibrillation shocks with three defibrillation systems: an implantable cardioverter defibrillator (ICD), a subcutaneous ICD (S-ICD), and an external cardioverter defibrillator (ECD). Each system delivered a series of bipolar high-energy shocks and reverse-polarity high-energy shocks.ResultsThe specified cardiac defibrillation shocks were delivered successfully from each of the three defibrillation systems to all animals. After each shock series, interrogation of the IPG confirmed that software and data were unchanged from pre-programmed values. After all of the defibrillation shocks were delivered, the IPGs underwent and passed comprehensive electrical testing demonstrating proper system function. No shifts in IPG parameters or ART system failures were observed, and histologic evaluation of the vagus nerve revealed no anatomic changes.ConclusionsImplantable VNS systems were tested in vivo for immunity to defibrillation via ICD, S-ICD, and ECD, and were found to be unaffected by a series of high-energy defibrillation shocks. These results confirm that ART systems are capable of continuing to function after defibrillation and the cervical vagus nerve is anatomically unaffected.

What is the optimal frequency in shock wave lithotripsy for pediatric renal stones? A prospective randomized study.

The aim of the study is to compare the effects of varying frequency rates (60, 90, and 120SWs/min) on the stone free rate and complication rates of pediatric SWL. 75 children with renal stones were divided into 3 groups depending on the SW frequency applied. Group 1. low (60SWs/min), Group 2. intermediate (90 SWs/min) and Group 3. high (120 SWs/min) frequency. Patient demographics (age, gender, BMI), stone (location, size, laterality), and SWL (total number of sessions, shock waves, anesthesia time) related parameters were documented. Postoperative success, complication rates, and the need for additional interventions were comparatively evaluated. There was no significant difference regarding the patient demographics, stone characteristics, SWL parameters, postoperative complication rates, need for additional interventions as well as efficacy quotient between all (p > 0.05). The stone free rates were significantly lower in cases with high frequency, whereas there was no statistically significant difference between the intermediate and low frequency groups (p > 0.05). Although not statistically significant; low frequency application may be more advantageous than intermediate as lower number of high energy shock waves required which may cause less tissue damage. On the other hand, despite lack of a statistically significant difference, relatively longer anesthesia time may constitute a disadvantage for lower frequency. We believe that considering the growing nature of the child kidney application of low frequency (60SWs/min) will be advantageous. However, we believe that further studies with larger series of cases are needed to make a clear-cut differentiation between low and intermediate SW applications.

Water-Jet Cavitation Shock Bulging as Novel Microforming Technique

With the continuous expansion of the application range of microelectromechanical systems, microdevice forming technology has achieved remarkable results. However, it is challenging to develop new microforming processes that are low cost, environmentally friendly, and highly flexible; the high-energy shock wave in a cavitation bubble’s collapse process is used as the loading force. Herein, a new process for the microbulging of the water-jet cavitation is proposed. A series of experiments involving the water-jet cavitation shock microbulging process for TA2 titanium foil is performed on an experimental system. The microforming feasibility of the water-jet cavitation is investigated by characterizing the shape of the formed part. Subsequently, the effects of the main parameters of the water-jet cavitation on the bulging profile, forming depth, surface roughness, and bulging thickness distribution of TA2 titanium foil are revealed. The results show that the plastic deformation increases nonlinearly with the incident pressure. When the incident pressure is 20 MPa, the maximum deformation exceeds 240 μm, and the thickness thinning ratio changes within 10%. The microbulging feasibility of water-jet cavitation is verified by this phenomenon.

Research on the water cavitation peening process and mechanism of TC4 titanium alloy

Cavitation water shot peening is a new processing method of surface strengthening and modification that utilizes the cavitation bubbles in the cavitation water jet to destroy high-energy shock waves, causing the cavitation groups to collapse on the surface of the material. Strengthening research on TC4 titanium alloy cavitation water jet peening is limited. The process of cavitation water shot peening strengthening is small, and the mechanism of residual stress generation is not yet clear. Therefore, five typical shot peening strength tests of TC4 titanium alloy are taken as examples in this paper. Experiments and mechanistic studies are carried out through macro-micromorphology, metallographic structure and XRD analysis, microhardness, and residual stress methods. The research results are as follows: as the shot peening strength increases, the surface roughness Ra and the depth of the plastic deformation layer gradually increase, and the depth of the plastic deformation layer is saturated at 55–60 μm; the depth of the influence of the microhardness and residual stress reaches 130 μm; and the surface grains gradually refine and develop to the nanometre level.

The shocking lack of significant increases in high sensitivity troponin values after cardioversion

Abstract Background and introduction Cardioversion is commonly used to terminate cardiac arrhythmias. Some previous reports have suggested that cardioversion results in myocardial injury as evidenced by increased levels of cardiac troponin. However, many of these studies were done years ago with less sensitive troponin assays and monophasic waveform defibrillators. Purpose To determine if external direct current (DC) cardioversion with biphasic rectilinear waveform shocks results in myocardial injury as assessed by high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI). Methods Patients scheduled for elective DC cardioversion for atrial fibrillation or atrial flutter were recruited. Plasma samples for measurement of hs-cTnT and hs-cTnI were obtained pre-cardioversion and as late as feasible but at least 6 hours post-cardioversion [median of 9 (7–11) hours]. Results A total of 96 patients were recruited. One patient was excluded because the pre-cardioversion sample was hemolysed. Median (25th–75th interquartile range) cumulative energy delivered was 121.6J (62.4–277.4J) and median highest energy individual shock was 121.0J (62.1–146.2J). A total of 39 (41.1%) patients received more than 1 shock, 23 (24.2%) patients received a cumulative energy of 300J or higher and 5 (5.3%) patients received a cumulative energy of 1,000J or more. The median pre-cardioversion hs-cTnT value was 11.48 (7.19–18.38) ng/L and the median hs-cTnI value was 5.1 (2.0–9.4) ng/L. Median post-cardioversion hs-cTnT value were 12.46 (7.98–20.28) ng/L and hs-cTnI value were 6.3 (3.5–10.0) ng/L. Wilcoxon-Signed ranks test showed a statistically significant change between the pre-and-post cardioversion hs-cTnT values (Z=−4.237, p&amp;lt;0.001) and hs-cTnI values (Z=−4.822, p&amp;lt;0.001). In only 5 (hs-cTnT) and 4 patients (hs-cTnI) was there an increase of &amp;gt;5 ng/L. There were 5 cases where the post-cardioversion values of both hs-cTnT and hs-cTnI were above the 50% reference change value. There was no relation between the change in hs-cTn values and sex, number of shocks, total energy delivered (even in those who received more than 1,000J), highest energy per shock, total current delivered, highest current delivered per shock or transthoracic impedance. Conclusion(s) There is a statistically significant but very small change in median hs-cTnT and hs-cTnI values (1 ng/L and 1.2 ng/L respectively) after DC cardioversion. The results were similar even in patients where high energy shocks were delivered and did not vary based on the pre cardioversion baseline value. Patients who have marked troponin elevations after cardioversion should be assessed for other causes of myocardial injury. It should not be assumed that they have myocardial injury from the cardioversion alone. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): Dr. Allan Jaffe has substantial research funds from both grants and private industry. Funds were used to pay for blood sample collection and analysis of high sensitivity cardiac troponin T at Mayo Clinic. Abbott Laboratories donated reagents for the high sensitivity cardiac troponin I analysis.

Impact of shock waves on glass wool composition and properties

Glass wool finds its application in soundproofing materials and insulation. This paper studies the effect of high-energy shock waves on glass wool fibres using modified Reddy shock tube. Changes in composition and properties of fibres are reported through SEM analysis. With driver pressure of 6.79 bar, Mach number, maximum pressure and temperature achieved are 1.46, 4.845 atm and 482.91 K respectively. Due to diaphragm material, carbon content of 2.92% by weight is observed in shocked specimen. SEM images show curliness in fibers, increased number and uniform distribution of binder clusters and air voids resulting in enhanced strength, hardness and insulation properties of fibres.

Comparison of scaphoid reconstruction with a non-vascularised bone graft, with and without shock waves; preliminary results

Focused, high energy shock wave therapy (ESWT) stimulates bone healing by neo-angiogenesis and activating osteocytes. This study investigates if applying an ESWT intraoperatively improves and accelerates the healing of a scaphoid nonunion after reconstruction using a non-vascularized bone graft. In this prospective, ongoing study, patients with a scaphoid reconstruction using a non-vascularized bone graft and stabilization for non-union, are randomized for having additionally an intraoperative ESWT (intervention group) or not (control group). In 6 weeks-intervals, patients have a clinical and radiological follow-up, including a CT scan at 12, 18, and if needed 24 weeks postoperatively. The intervention group and the control group are compared with regard to the proportion of the bridged contact area between scaphoid and the bone graft at 12, 18, and 24 weeks postoperatively and the rate of the healed scaphoids at the final follow-up. At time of this data analysis, 35 patients of the intervention group and 33 patients of the control group had passed all of their scheduled follow-ups. Twenty-four weeks postoperatively, the scaphoids of 27 patients (77 %) in the intervention group and those of 20 patients (61 %) in the control group were healed. At 12, 18, and 24 weeks, the contact area between scaphoid and the bone graft proximally was bridged by 80 %, 84 %, and 86 % respectively in the intervention group, and 74 %, 81 %, and 84 % in the control group. Distal to the bone graft, the gap was bridged by 91 %, 94 %, and 95 % for the intervention group and 77 %, 90 %, and 94 % for the control group. At 12 weeks postoperatively, the proportional healing distal to the bone graft was significantly higher after ESWT. A single, intraoperative ESWT improves the healing rate of scaphoid reconstruction with a non-vascularized bone graft and accelerates the gap bridging during the first 12 weeks after surgery.

Progressive implantable cardioverter-defibrillator therapies for ventricular tachycardia: The efficacy and safety of multiple bursts, ramps, and low-energy shocks

The Heart Rhythm Society, the European Heart Rhythm Association, the Asia Pacific Heart Rhythm Society, the Latin American Heart Rhythm Society expert consensus statement on optimal implantable cardioverter-defibrillator programming recommends burst antitachycardia pacing (ATP) for the treatment of ventricular tachycardia (VT) up to high rates. The number of bursts is not specified, and treatment by ramps or low-energy shocks is not recommended. We investigated the efficacy and safety of progressive therapies for VTs between 150 and 200 beats/min. After 3 failed bursts, we compared 3 ramps vs 3 bursts followed by a low-energy shock vs high-energy shock. Using remote monitoring, we included monomorphic VT episodes treated with ≥1 burst. A total of 1126 VT episodes were included. A single burst was as likely to terminate VT between 150 and 200 beats/min as VT between 200 and 230 beats/min (63% vs 64%; P=.41), but was more likely to accelerate the latter (3.2% vs 0.25%; P<.01). For VT <200 beats/min, the likelihood of ATP success increased progressively (73% with 2 bursts, 78% with 3 bursts). Three additional bursts further increased VT termination to 89%, similar to the success rate with 3 additional ramps (88%; P=.17). Programming 6 bursts is associated with the probability of acceleration requiring shock of 6.6%. A low-energy first shock was less successful than a high-energy shock (66% vs 86%; P<.01) and more likely to accelerate VT (17% vs 0%; P<.01). Programming up to 6 burst ATP therapies for VTs 150-200 beats/min can avoid implantable cardioverter-defibrillator shocks in most patients. Ramp ATP after failed bursts were similarly effective. Low-energy shocks are less effective and more arrhythmogenic than high-energy shocks.

A Computer Model for Patient Individual Parametrizing of Ventricular Tachycardia Termination Algorithms.

Antitachycardial pacing (ATP) is a painless method for terminating ventricular tachycardias (VT) which would otherwise be treated using a painful high energy shock. However, it is well known that not each VT can be successfully terminated by ATP. Furthermore, ATP can be parametrized in several ways using scan, ramp or scan ramp approaches and can be applied in the right ventricle or in both ventricles (biventricular). In this work, we investigate the therapeutically most convenient ATP protocol based on a computer simulation using a patient individual model. A patient individual model generated from a 3D/4D data set and a hybrid automaton was used for modeling and simulation of different VT scenarios. On the different VTs (from cycle length 288 ms up to 408 ms) different ATP approaches derived from the ADVANCE-CRT trial were applied in order to determine the effectiveness of these approaches. In this computer simulation study we were able to verify and validate the results from the ADVANCE-CRT trial. Biventricular ATP does not prove to be more effective than RV ATP but has a slight advantage in terminating fast VTs. The availability of a patient individual model and knowledge about the ischemic area and the underlying mechanism of the VTs will allow the use of these models to optimize ATP management.

Zinc Oxide Nanocrystals and High-Energy Shock Waves: A New Synergy for the Treatment of Cancer Cells

In the last years, different nanotools have been developed to fight cancer cells. They could be administered alone, exploiting their intrinsic toxicity, or remotely activated to achieve cell death. In the latter case, ultrasound (US) has been recently proposed to stimulate some nanomaterials because of the US outstanding property of deep tissue penetration and the possibility of focusing. In this study, for the first time, we report on the highly efficient killing capability of amino-propyl functionalized ZnO nanocrystals (ZnO NCs) in synergy with high-energy ultrasound shock waves (SW) for the treatment of cancer cells. The cytotoxicity and internalization of ZnO NCs were evaluated in cervical adenocarcinoma KB cells, as well as the safety of the SW treatment alone. Then, the remarkably high cytotoxic combination of ZnO NCs and SW was demonstrated, comparing the effect of multiple (3 times/day) SW treatments toward a single one, highlighting that multiple treatments are necessary to achieve efficient cell death. At last, preliminary tests to understand the mechanism of the observed synergistic effect were carried out, correlating the nanomaterial surface chemistry to the specific type of stimulus used. The obtained results can thus pave the way for a novel nanomedicine treatment, based on the synergistic effect of nanocrystals combined with highly intense mechanical pressure waves, offering high efficiency, deep and focused tissue penetration, and a reduction of side effects on healthy cells.

Antitachycardia pacing for shock prevention in patients with hypertrophic cardiomyopathy and ventricular tachycardia

Hypertrophic cardiomyopathy (HCM) carries an increased risk of sudden death due to ventricular arrhythmias (VAs). The implantable cardioverter-defibrillator (ICD) is a well-established therapy for treatment of VA. Monomorphic ventricular tachycardias (MVTs) are frequent in HCM patients and suitable for antitachycardia pacing (ATP) termination. The purpose of this study was to describe ventricular tachycardia (VT) characteristics in a population of HCM patients with ICD and to study the effectiveness and safety of ATP for MVT. Data were obtained from the multicenter prospective observational UMBRELLA trial, which included all patients with HCM and ICD followed by the CareLink Monitoring System. All episodes of VA were collected and analyzed. ATP effectiveness and safety were described, and factors related to ATP effectiveness were studied with generalized estimating equation (GEE) models. Among 251 patients followed for 47 months, 67 (26.7%) were implanted as secondary prevention. Fifty-six patients presented 326 episodes of VA (286 [87%] MVT). Mean cycle length was 312 ± 64 ms. Among 264 MVTs that received ICD therapy, 202 (76.5%) were ATP terminated. The first ATP burst was effective in 169 episodes (68.4%), and overall effectiveness of the first or second ATP burst was 73.8%. Multivariate GEE-adjusted analysis showed 2 variables related to ATP effectiveness: programming fast VT zone On vs Off (odds ratio [OR] 2.4; 95% confidence interval [CI] 1.5-5.2; P = .03) and programming ≥2 ATP bursts vs 1 burst only (OR 1.6; 95% CI 1.2-3.4; P = .04; and OR 2.9; 95% CI 1.8-6.3; P = .02; respectively). MVT is the predominant VA in HCM patients with ICD. ATP is highly effective in terminating the majority of MVTs, and its proved effectiveness should guide device selection and programming in order to avoid unnecessary high-energy shocks.