Delivery of Cardioactive Therapeutics in a Porcine Myocardial Infarction Model.

Myocardial infarction is one of the leading causes of death and disability worldwide, and there is an urgent need for novel cardioprotective or regenerative strategies. An essential component of drug development is determining how a novel therapeutic is to be administered. Physiologically relevant large animal models are of critical importance in assessing the feasibility and efficacy of various therapeutic delivery strategies. Due to their similarities to humans in cardiovascular physiology, coronary vascular anatomy, and heart weight to body weight ratio, swine is one of the preferred species in the preclinical evaluation of new therapies for myocardial infarction. The present protocol describes three methods of administering cardioactive therapeutic agents in a porcine model. After percutaneously induced myocardial infarction, female landrace swine received treatment with novel agents through either: (1) thoracotomy and transepicardial injection, (2) catheter-based transendocardial injection, or (3) intravenous infusion via jugular vein osmotic minipump. The procedures employed for each technique are reproducible, resulting in reliable cardioactive drug delivery. These models can be easily adapted to suit individual study designs, and each of these delivery techniques can be used to investigate a variety of possible interventions. Therefore, these methods are a useful tool for translational scientists pursuing novel biological approaches in cardiac repair following myocardial infarction.

Text messages promoting healthy lifestyle and linked with activity monitors stimulate an immediate increase in physical activity among women after gestational diabetes.

AIMS: To evaluate the immediate effect of text messages promoting healthy lifestyle and supporting parenting on physical activity amongst women with recent gestational diabetes (GDM). METHODS: Analysis of data from a pilot randomised controlled trial of a healthy lifestyle program for women with recent GDM. Intervention subjects received text messages providing motivation, reminders, information and feedback as well as an activity monitor. This sub-study examined step count in the 4 h after receipt of a text message, compared to the same time of day on other days among intervention subjects. RESULTS: Data from 7326 days where step counts were recorded, from 31 women were analysed. The median steps in the 4 h following a text message was 1237 (IQR 18-2240) and it was 1063 (IQR 0-2038) over the same time period on comparison days where there was no message (p < 0.001). The effect was similar whether the messages pertained to physical activity or not. There was no attenuation of the response over 36-38 weeks. CONCLUSIONS: Women with recent GDM increase their step count in the hours following positive and supportive text messages. This suggests that text messaging programs can facilitate healthy lifestyle and diabetes prevention in this population.

Electrical Impedance Tomography for monitoring cardiac radiofrequency ablation: a scoping review of an emerging technology.

Arrhythmias are common cardiac diseases which can be treated effectively by the cardiac radiofrequency ablation (CRFA). However, information regarding the lesion growth within the myocardium is critical to the procedure's safety and efficacy but still unavailable in the current catheterisation lab (CathLab). Over the last 20 years, many efforts have been made in order to track the lesion size during the procedure. Unfortunately, all the approaches have their own limitations preventing them from the clinical translation and hence making the lesion size monitoring during a CRFA still an open issue. Electrical Impedance Tomography (EIT) is an impedance imaging modality that might be able to image the thermal-related impedance changes from which the lesion size can be measured. With the availability of the patient's CT scans, for a detailed model, and the catheter-based electrodes for the internal electrodes, EIT accuracy and sensitivity to the ablated sites can be significantly improved and is worth being explored for this application. Though EIT is still new to CRFA with no in-vivo experiments being done according to our up-to-date searching, many related EIT studies and its extensive research in Hyperthermia and other ablations can reveal many hints for a possibility of the CRFA-EIT application. In this paper, we present a review on multiple aspects of EIT in CRFA. First, the expected CRFA-EIT signal range and frequency are discussed based on various measured impedance results obtained from lesions in the past. Second, the possible noise sources that can happen in a clinical CRFA procedure, along with their signal range and frequency compared to the CRFA-EIT signal, and, third, the available current solutions to separate such noises from the CRFA-EIT signal. Finally, we review the progress of EIT in thermal applications over the last two decades in order to identify the developments that EIT can take advantage of and the current drawbacks that need to be solved for a potential CRFA-EIT application.

Cardiac radiofrequency ablation tracking using electrical impedance tomography.

There is a need for accessible high speed imaging of Radiofrequency (RF) cardiac electrosurgery to improve safety and efficacy of the ablation time course, where lesion information is critical to safety and efficacy but currently lacking in real time. In this paper, Electrical Impedance Tomography (EIT) using existing cardiac EP electrodes was optimised to confirm (1) that removal of measurements with low signal sensitivity leads to improved images and (2) that multiple signal thresholds are needed to track the lesion accurately over time. A novel ventricle-shaped gel phantom with realistic fluid flow to mimic blood flow, lung ventilation and myocardium conductivity was developed to study the capability and motivate transition to in-vivo measurements. When using 8 external (ECG) electrodes, 4 internal coronary sinus electrodes and 4 RF catheter-based electrodes, the optimal setup for sensitivity and dynamic tracking was 77 measurements within an error of 20%. Higher thresholds were more suitable for the earlier phase of the ablation when lesions are small while lower thresholds suited later phases. Patient-specific thresholds could be optimised in pre-surgical planning where detailed anatomical images are available. While the error reported in this initial study appears large, it is a major advance over the current situation for the cardiologist where no real-time lesion visualization is accessible in a regular EP suite/cath lab.

Self-weighted NOSER-prior electrical impedance tomography using internal electrodes in cardiac radiofrequency ablation.

OBJECTIVE: Radiofrequency (RF) cardiac ablation is a commonly used method for treating cardiac arrhythmias in which the information of the dynamic lesion heating is critical to cardiologists but is currently lacking. Electrical impedance tomography (EIT) is a temporal modality of imaging the changes in the electrical properties within a measured object and hence might be able to track the electrical variation due to temperature changes within the myocardium. Within this paper, (1) a time-efficient algorithm with self-weighted NOSER-prior and (2) a measurement filtering process for optimizing the number of measurement were proposed for monitoring the lesion size during the cardiac RF ablation, taking advantage of internal catheter-based electrodes and the prior information of anatomical structure and the catheter location, which are usually available during the ablation course. APPROACH: A tank model with a circular myocardium of 12 mm in thickness, 16 external electrodes on the boundary and three internal catheter-based electrodes positioned inside the endocardium were made. The ablations were simulated using Pennes' bioheat transfer equation and the simulated temperature gradients were then transferred to EIT measurements. The algorithm used one reference ablation for its optimization and then was tested with numerous 90 s ablations containing three disturbances: the catheter location mapping, the wide range of varied myocardium conductivity and the blood's cooling convection, and the Gaussian noises with 10-40 µV in standard deviation. MAIN RESULTS: The results showed that, with the optimized number of 55 measurements, the algorithm still performed well when dealing with all three disturbances plus the random noises up 25 µV. Specifically, the lesion depth and width were measured within 1.6 mm and 3.2 mm in error respectively in at least 80% out of 100 simulated ablations. SIGNIFICANCE: The algorithm has successfully measured the lesion size with good accuracy and tolerances of noise and other system perturbations. More tests in vitro and in vivo are required in the future to confirm the algorithm's feasibility.

A Pilot Randomised Controlled Trial of a Text Messaging Intervention with Customisation Using Linked Data from Wireless Wearable Activity Monitors to Improve Risk Factors Following Gestational Diabetes.

Gestational diabetes (GDM) is a highly prevalent disorder of pregnancy which portends a high risk for future type 2 diabetes. Limited evidence indicates lifestyle intervention prevents the development of diabetes, but most previously studied interventions are resource-intensive. Intervention programs that utilise newer technologies may be scalable at lower cost. This 6-month pilot randomized controlled trial tested the delivery of text messages linked to an activity monitor, adaptive physical activity goal setting, and limited face-to-face counseling, as an intervention to improve rates of post-partum glucose tolerance testing and lifestyle behaviours amongst women following a GDM pregnancy. Sixty subjects were randomised 2:1 intervention vs. control. Compared to control subjects, there were trends for intervention subjects to improve diet, increase physical activity, and lose weight. There was no difference between the groups in the rate of glucose tolerance testing. Only 46 (77%) subjects completed some, and 19 subjects completed all the elements of the final evaluation. Feedback regarding the text messages and activity monitor was highly positive. Overall, results suggest that a text message and activity monitor intervention is feasible for a larger study or even as a potentially scalable population health intervention. However, low completion rates necessitate carefully considered modification of the protocol.

Experimental Validation of the Multiphysics Modelling of Radiofrequency Ablation using Physical Phantom.

Spastic Cerebral Palsy is the most common type of Cerebral Palsy (CP) that affects muscle coordination and control. Using Radiofrequency Ablation (RFA) to target the motor branches of the median and ulnar nerve may provide an additional treatment to Botulinum Toxin for spasticity in the hand. However, there are a limited number of studies that report the use of RFA in treating upper-limb spasticity. This prompts the need to establish a simulation model that has been tested against physical phantom to help determine the efficacy of RFA as a treatment for spasticity. In this study, a 3D COMSOL Multiphysics model of a commercial RF probe was validated against a Thermochromic Liquid Crystal (TLC) homogeneous gel phantom. The results of the COMSOL model were compared to the TLC phantom in terms of temperature (0.42 ± 1.06°C for the TLC high temperature range and -1.90 ± 0.88°C for the TLC low temperature range), lesion shape (14.5 ± 5.0%) and lesion size (0.18 ± 0.06 mm). These results show that COMSOL Multiphysics may be feasible as a tool to characterise RF lesions if the reported errors are accounted for. Further work is required to develop a more complex COMSOL model that incorporates different tissue aspects. However, this is a first step to establishing a validated COMSOL model of a RF probe in homogeneous muscle tissue.

Five seconds of 50-60 W radio frequency atrial ablations were transmural and safe: an in vitro mechanistic assessment and force-controlled in vivo validation.

AIMS: Longer procedural time is associated with complications in radiofrequency atrial fibrillation ablation. We sought to reduce ablation time and thereby potentially reduce complications. The aim was to compare the dimensions and complications of 40 W/30 s setting to that of high-power ablations (50-80 W) for 5 s in the in vitro and in vivo models. METHODS AND RESULTS: In vitro ablations-40 W/30 s were compared with 40-80 W powers for 5 s. In vivo ablations-40 W/30 s were compared with 50-80 W powers for 5 s. All in vivo ablations were performed with 10 g contact force and 30 mL/min irrigation rate. Steam pops and depth of lung lesions identified post-mortem were noted as complications. A total of 72 lesions on the non-trabeculated part of right atrium were performed in 10 Ovine. All in vitro ablations except for the 40 W/5 s setting achieved the critical lesion depth of 2 mm. For in vivo ablations, all lesions were transmural, and the lesion depths for the settings of 40 W/30 s, 50 W/5 s, 60 W/5 s, 70 W/5 s, and 80 W/5 s were 2.2 ± 0.5, 2.3 ± 0.5, 2.1 ± 0.4, 2.0 ± 0.3, and 2.3 ± 0.7 mm, respectively. The lesion depths of short-duration ablations were similar to that of the conventional ablation. Steam pops occurred in the ablation settings of 40 W/30 s and 80 W/5 s in 8 and 11% of ablations, respectively. Complications were absent in short-duration ablations of 50 and 60 W. CONCLUSION: High-power, short-duration atrial ablation was as safe and effective as the conventional ablation. Compared with the conventional 40 W/30 s setting, 50 and 60 W ablation for 5 s achieved transmurality and had fewer complications.

Design Considerations in Development of a Mobile Health Intervention Program: The TEXT ME and TEXTMEDS Experience.

BACKGROUND: Mobile health (mHealth) has huge potential to deliver preventative health services. However, there is paucity of literature on theoretical constructs, technical, practical, and regulatory considerations that enable delivery of such services. OBJECTIVES: The objective of this study was to outline the key considerations in the development of a text message-based mHealth program; thus providing broad recommendations and guidance to future researchers designing similar programs. METHODS: We describe the key considerations in designing the intervention with respect to functionality, technical infrastructure, data management, software components, regulatory requirements, and operationalization. We also illustrate some of the potential issues and decision points utilizing our experience of developing text message (short message service, SMS) management systems to support 2 large randomized controlled trials: TEXT messages to improve MEDication adherence & Secondary prevention (TEXTMEDS) and Tobacco, EXercise and dieT MEssages (TEXT ME). RESULTS: The steps identified in the development process were: (1) background research and development of the text message bank based on scientific evidence and disease-specific guidelines, (2) pilot testing with target audience and incorporating feedback, (3) software-hardware customization to enable delivery of complex personalized programs using prespecified algorithms, and (4) legal and regulatory considerations. Additional considerations in developing text message management systems include: balancing the use of customized versus preexisting software systems, the level of automation versus need for human inputs, monitoring, ensuring data security, interface flexibility, and the ability for upscaling. CONCLUSIONS: A merging of expertise in clinical and behavioral sciences, health and research data management systems, software engineering, and mobile phone regulatory requirements is essential to develop a platform to deliver and manage support programs to hundreds of participants simultaneously as in TEXT ME and TEXTMEDS trials. This research provides broad principles that may assist other researchers in developing mHealth programs.

Effect of Lifestyle-Focused Text Messaging on Risk Factor Modification in Patients With Coronary Heart Disease: A Randomized Clinical Trial.

IMPORTANCE: Cardiovascular disease prevention, including lifestyle modification, is important but underutilized. Mobile health strategies could address this gap but lack evidence of therapeutic benefit. OBJECTIVE: To examine the effect of a lifestyle-focused semipersonalized support program delivered by mobile phone text message on cardiovascular risk factors. DESIGN AND SETTING: The Tobacco, Exercise and Diet Messages (TEXT ME) trial was a parallel-group, single-blind, randomized clinical trial that recruited 710 patients (mean age, 58 [SD, 9.2] years; 82% men; 53% current smokers) with proven coronary heart disease (prior myocardial infarction or proven angiographically) between September 2011 and November 2013 from a large tertiary hospital in Sydney, Australia. INTERVENTIONS: Patients in the intervention group (n = 352) received 4 text messages per week for 6 months in addition to usual care. Text messages provided advice, motivational reminders, and support to change lifestyle behaviors. Patients in the control group (n=358) received usual care. Messages for each participant were selected from a bank of messages according to baseline characteristics (eg, smoking) and delivered via an automated computerized message management system. The program was not interactive. MAIN OUTCOMES AND MEASURES: The primary end point was low-density lipoprotein cholesterol (LDL-C) level at 6 months. Secondary end points included systolic blood pressure, body mass index (BMI), physical activity, and smoking status. RESULTS: At 6 months, levels of LDL-C were significantly lower in intervention participants, with concurrent reductions in systolic blood pressure and BMI, significant increases in physical activity, and a significant reduction in smoking. The majority reported the text messages to be useful (91%), easy to understand (97%), and appropriate in frequency (86%). [table: see text]. CONCLUSIONS AND RELEVANCE: Among patients with coronary heart disease, the use of a lifestyle-focused text messaging service compared with usual care resulted in a modest improvement in LDL-C level and greater improvement in other cardiovascular disease risk factors. The duration of these effects and hence whether they result in improved clinical outcomes remain to be determined. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12611000161921.

Observations on Attenuation of Local Electrogram Amplitude and Circuit Impedance During Atrial Radiofrequency Ablation: An In vivo Investigation Using a Novel Direct Endocardial Visualization Catheter.

AIMS: To define the temporal characteristics of atrial lesion growth (lesion surface area), local electrogram amplitude attenuation, and circuit impedance decrement during in vivo radiofrequency (RF) ablation with direct endocardial visualization (DEV). METHODS AND RESULTS: A direct endocardial visualization catheter was used for real-time endoscopic visualization of atrial endocardial surface during RF ablation. Videos of lesion growth (surface area), circuit impedance, and local electrogram amplitude were recorded during ablation in 11 ovine. Fifty-two atrial ablations at 12 W, 14 W, and 16 W power for 30 seconds were analyzed. During 30-second RF ablation, the lesion matured (90% of final lesion dimension) in the first 23.0 ± 5.8 seconds. The local electrogram amplitude attenuation (80% decrement) and circuit impedance attenuation (20% decrement from initial) occurred 13.8 ± 8.2 seconds and 13.1 ± 7.9 seconds, respectively, before lesion maturity in a significant proportion of 30 second atrial ablations. CONCLUSION: The DEV observations suggest that in smooth atrial surface ablations with significant local electrogram and impedance decrement in the first 10 seconds, further extension of ablation for 10-15 seconds could deliver optimal surface dimensions; however, real-time measurement of depth was not possible.