Targeting Wavefront Discontinuity Lines for Scar-Related Ventricular Tachycardia Ablation: A Novel Functional Substrate Ablation Approach.

BACKGROUND: The boundaries of critical isthmuses for re-entrant ventricular tachycardia (VT) are formed by wave-front discontinuities (fixed lines of block, slow propagation, and rotational propagation) seen during baseline rhythm. It is unknown whether wavefront discontinuities can be automatically identified and targeted for ablation using electroanatomic mapping systems. OBJECTIVES: The purpose of this study was to assess the electrophysiologic characteristics of automatically projected wavefront discontinuity lines (WADLs) and outcomes of an ablation strategy targeting WADLs in a mixed cohort of VT patients. METHODS: Late activation substrate maps were analyzed from 1 or more baseline rhythm wavefronts. WADLs were identified using the Carto Extended Early Meets Late module. Number, total length, and distance to critical VT sites were measured. VT recurrence and VT-free survival were followed. RESULTS: In total, 49 patients underwent 52 ablations with 71 unique substrate maps analyzed (18.8% epicardial; 62.0% right ventricular paced, 28.2% sinus rhythm, 9.9% left ventricular paced). A total of 28 VT critical sites were identified in 24 patients. WADLs were present in 49 of 71 (69.0%) maps. WADLs were present regardless of cardiomyopathy etiology, mapping wavefront, or surface. At a WADL threshold of 30%, 73.9% of critical VT sites were in close proximity (≤15 mm) to a WADL. VT-free survival was 62% at 1 year, with a competing risk model estimating a 1-year risk of VT recurrence of 23%. CONCLUSIONS: WADLs can be automatically projected in a majority of patients in a mixed cohort of cardiomyopathy etiology, mapped wavefronts, and myocardial surfaces mapped. Targeting WADLs results in low rate of VT recurrence at 1 year.

Low-energy (360 J) radiofrequency catheter ablation using moderate power - short duration: proof of concept based on in silico modeling.

BACKGROUND: Pilot clinical studies suggest that very high power-very short duration (vHPvSD, 90 W/4 s, 360 J energy) is a feasible and safe technique for ablation of atrial fibrillation (AF), compared with standard applications using moderate power-moderate duration (30 W/30 s, 900 J energy). However, it is unclear whether alternate power and duration settings for the delivery of the same total energy would result in similar lesion formation. This study compares temperature dynamics and lesion size at different power-duration settings for the delivery of equivalent total energy (360 J). METHODS: An in silico model of radiofrequency (RF) ablation was created using the Arrhenius function to estimate lesion size under different power-duration settings with energy balanced at 360 J: 30 W/12 s (MPSD), 50 W/7.2 s (HPSD), and 90 W/4 s (vHPvSD). Three catheter orientations were considered: parallel, 45°, and perpendicular. RESULTS: In homogenous tissue, vHPvSD and HPSD produced similar size lesions independent of catheter orientation, both of which were slightly larger than MPSD (lesion size 0.1 mm deeper, ~ 0.7 mm wider, and ~ 25 mm3 larger volume). When considering heterogeneous tissue, these differences were smaller. Tissue reached higher absolute temperature with vHPvSD and HPSD (5-8 °C higher), which might increase risk of collateral tissue injury or steam pops. CONCLUSION: Ablation for AF using MPSD or HPSD may be a feasible alternative to vHPvSD ablation given similar size lesions with similar total energy delivery (360 J). Lower absolute tissue temperature and slower heating may reduce risk of collateral tissue injury and steam pops associated with vHPvSD and longer applications using moderate power.

Very early versus early referral for ablation in young patients with newly diagnosed paroxysmal atrial fibrillation.

BACKGROUND: Catheter ablation (CA) has emerged as an effective therapy for the treatment of paroxysmal atrial fibrillation (AF); however it is unclear whether proceeding expeditiously to CA improves clinical outcomes in a real-world population. This study compares outcomes of CA for new AF within 6 months of diagnosis (very early) 6 to 12 months after diagnosis (early) and 12 to 24 months after diagnosis (later). METHODS: A large nationally-representative sample of patients ages 18 to 64 who underwent CA from January 2011 to June 2019 was studied using the IBM MarketScan Database. The primary outcome was a composite of healthcare utilization over the following 24 months. Propensity score-matching was used to match patients in each cohort. Risk difference in outcomes were compared between matched patients. RESULTS: Two thousand six hundred thirty one patients were identified postmatching, with 1649 in the very early cohort and 982 in the early cohort. The very early referral group was less likely to experience the primary composite outcome postablation (Absolute risk difference [ARD]: -3.9%; 95% Confidence interval [CI]: -5.8%, -2.0%), with the difference driven by fewer cardioversions (ARD: -2.9%, 95% CI: -5.3%, -0.5%) and outpatient visits (ARD: -6.6%, 95% CI: -10.5%, -2.7%). There was no difference in outcomes between early and later referral groups, with only very early referral showing decreased healthcare utilization. CONCLUSIONS: Patients who underwent ablation within 6 months of diagnosis had lower healthcare utilization in the ensuing 24 months, driven by fewer outpatient visits and cardioversions, supporting expeditious referral for ablation for symptomatic AF.

Limited duration of antiarrhythmic drug use for newly diagnosed atrial fibrillation in a nationwide population under age 65.

INTRODUCTION: Antiarrhythmic drugs (AADs) are commonly used for the treatment of newly diagnosed symptomatic atrial fibrillation (AF), however initial AAD choice, duration of therapy, rates of discontinuation, and factors associated with a durable response to therapy are poorly understood. This study assesses the initial choice and duration of antiarrhythmic drug therapy in the first 2 years after diagnosis of AF in a younger, commercially insured population. METHODS: A large nationally representative sample of patients age 20-64 was studied using the IBM MarketScan Database. Patients who started an AAD within 90 days of AF diagnosis with continuous enrollment for 1-year pre-index diagnosis and 2 years post-index were included. A Cox proportional hazards model was used to determine factors associated with AAD discontinuation. RESULTS: Flecainide was used most frequently (26.8%), followed by amiodarone (22.5%), dronedarone (18.3%), sotalol (15.8%), and propafenone (14.0%), with other AADs used less frequently. Twenty-two percent of patients who started on an AAD underwent ablation within 2 years, with 79% discontinuing the AAD after ablation. Ablation was the strongest predictor of AAD discontinuation (hazard ratio [HR], 1.70; 95% confidence interval [CI]: 1.61-1.80), followed by the male gender (HR, 1.10; CI: 1.02-1.19). Older patients (HR, 0.76; CI: 0.72-0.80; reference age 18-49) and those with comorbidities, including cardiomyopathy (HR, 075; CI: 0.61-0.91), diabetes (HR, 0.83; CI: 0.75-0.91), and hypertension (HR, 0.87; CI: 0.81-0.94) were less likely to discontinue AADs. CONCLUSION: Only 31% of patients remained on the initial AAD at 2 years, with a mean duration of initial therapy 7.6 months before discontinuation.

Trends and predictors of early ablation for Atrial Fibrillation in a Nationwide population under age 65: a retrospective observational study.

BACKGROUND: Catheter ablation (CA) has emerged as an effective treatment for symptomatic atrial fibrillation (AF). However practice patterns and patient factors associated with referral for CA within the first 12 months after diagnosis are poorly characterized. This study examined overall procedural trends and factors predictive of catheter ablation for newly-diagnosed atrial fibrillation in a young, commercially-insured population. METHODS: A large nationally-representative sample of patients age 20 to 64 from years 2010 to 2016 was studied using the IBM MarketScan® Commercial Database. Patients were included with a new diagnosis of AF in the inpatient or outpatient setting with continuous enrollment for at least 1 year pre and post index visit. Patients were excluded if they had prior history of AF or had filled an anti-arrhythmic drug (AAD) in the pre-index period. RESULTS: Early CA increased from 5.0% in 2010 to 10.5% in 2016. Patients were less likely to undergo CA if they were located in the Northeast (OR: 0.80, CI: 0.73-0.88) or North Central (OR: 0.91, CI: 0.83-0.99) regions (compared with the West), had higher CHA2DS2-VASc scores, or had Charlson Comorbidity Index (CCI) score of 3 or greater (OR: 0.61; CI: 0.51-0.72). CONCLUSIONS: CA within 12 months for new-diagnosed AF increased significantly from 2010 to 2016, with most patients still trialed on an AAD prior to CA. Patients are less likely to be referred for early CA if they are located in the Northeast and North Central regions, have more comorbidities, or higher CHA2DS2-VASc scores.

Racial and insurance disparities among patients presenting with chest pain in the US: 2009-2015.

BACKGROUND: Nationally representative studies have shown significant racial and socioeconomic disparities in the triage and diagnostic evaluation of patients presenting to the emergency department (ED) with chest pain. However, these studies were conducted over a decade ago and have not been updated amidst growing awareness of healthcare disparities. OBJECTIVE: We aimed to reevaluate the effect of race and insurance type on triage acuity and diagnostic testing to assess if these disparities persist. METHODS: We identified ED visits for adults presenting with chest pain in the 2009-2015 National Hospital Ambulatory Health Care Surveys. Using weighted logistic regression, we examined associations between race and payment type with triage acuity and likelihood of ordering electrocardiography (ECG) or cardiac enzymes. RESULTS: A total of 10,441 patients met inclusion criteria, corresponding to an estimated 51.4 million patients nationwide. When compared with white patients, black patients presenting with chest pain were less likely to have an ECG ordered (adjusted odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.69-0.99). Patients with Medicare, Medicaid, and no insurance were also less likely to have an ECG ordered compared to patients with private insurance (Medicare: OR = 0.79, CI = 0.63-0.99; Medicaid: OR = 0.67, CI = 0.53-0.84; no insurance: OR = 0.68, CI = 0.55-0.84). Those with Medicare and Medicaid were less likely to be triaged emergently (Medicare: OR = 0.84, CI = 0.71-0.99; Medicaid: OR = 0.76, CI = 0.64-0.91) and those with Medicare were less likely to have cardiac enzymes ordered (OR = 0.84, CI = 0.72-0.98). CONCLUSIONS: Persistent racial and insurance disparities exist in the evaluation of chest pain in the ED. Compared to earlier studies, disparities in triage acuity and cardiac enzymes appear to have diminished, but disparities in ECG ordering have not. Given current Class I recommendations for ECGs on all patients presenting with chest pain emergently, our findings highlight the need for improvement in this area.

A Computationally Efficient Visual Saliency Algorithm Suitable for an Analog CMOS Implementation.

Computer vision algorithms are often limited in their application by the large amount of data that must be processed. Mammalian vision systems mitigate this high bandwidth requirement by prioritizing certain regions of the visual field with neural circuits that select the most salient regions. This work introduces a novel and computationally efficient visual saliency algorithm for performing this neuromorphic attention-based data reduction. The proposed algorithm has the added advantage that it is compatible with an analog CMOS design while still achieving comparable performance to existing state-of-the-art saliency algorithms. This compatibility allows for direct integration with the analog-to-digital conversion circuitry present in CMOS image sensors. This integration leads to power savings in the converter by quantizing only the salient pixels. Further system-level power savings are gained by reducing the amount of data that must be transmitted and processed in the digital domain. The analog CMOS compatible formulation relies on a pulse width (i.e., time mode) encoding of the pixel data that is compatible with pulse-mode imagers and slope based converters often used in imager designs. This letter begins by discussing this time-mode encoding for implementing neuromorphic architectures. Next, the proposed algorithm is derived. Hardware-oriented optimizations and modifications to this algorithm are proposed and discussed. Next, a metric for quantifying saliency accuracy is proposed, and simulation results of this metric are presented. Finally, an analog synthesis approach for a time-mode architecture is outlined, and postsynthesis transistor-level simulations that demonstrate functionality of an implementation in a modern CMOS process are discussed.

Diagnostic yield of device interrogation in the evaluation of syncope in an elderly population.

BACKGROUND: Device interrogation has become a standard part of the syncope evaluation for patients admitted with permanent pacemakers (PPM) or implantable cardiac defibrillators (ICD), although few studies have shown interrogation yields clinically useful data. The purpose of this study is to determine the diagnostic yield of device interrogation as well as other commonly performed tests in the workup of unexplained syncope in patients with previously implanted PPMs or ICDs. METHODS: We retrospectively reviewed records of 88 patients admitted to our medical center for syncope with previously implanted pacemakers between January 1, 2005 and January 1, 2015 using ICD-9 billing data. RESULTS: Pacemaker interrogation demonstrated an arrhythmia as the cause for syncope in 4 patients (4%) and evidence of device failure secondary to perforation in 1 patient (1%). The cause of syncope was unknown in 34 patients (39%). Orthostatic hypotension was the most commonly identified cause of syncope (26%), followed by vasovagal syncope (13%), autonomic dysfunction (5%), ventricular arrhythmia (3%), atrial arrhythmia (2%), congestive heart failure (2%), stroke (2%), and other less common causes (8%). History was the most important determinant of syncope (36%), followed by orthostatic vital signs (14%), device interrogations (4%), head CT (2%), and transthoracic echocardiogram (1%). CONCLUSIONS: Device interrogation is rarely useful for elucidating a cause of syncope without concerning physical exam, telemetry, or EKG findings. Interrogation may occasionally yield paroxysmal arrhythmias responsible for syncopal episode, but these rarely alter clinical outcomes. Interrogation appears to be more useful in patients with syncope after recent device placement.

Intrathecal Clonidine via Lumbar Puncture Decreases Blood Pressure in Patients With Poorly Controlled Hypertension.

OBJECTIVES: Oral clonidine is used to treat hypertension but often produces sedation and severe dry mouth; intrathecal clonidine is used to treat chronic pain but may produce hypotension. This clinical feasibility study was conducted to determine if intrathecal clonidine decreases blood pressure in patients with poorly controlled hypertension. MATERIALS AND METHODS: This prospective, single-arm, open-label study was conducted in ten subjects who were taking at least three antihypertensive medications including a diuretic and had an in-office systolic blood pressure between 140 and 190 mm Hg. On the day of treatment, blood pressure was measured before and after a single lumbar intrathecal dose (150 mcg) of clonidine using an automatic oscillometric device every 10-15 min for four hours. Student's paired t-test was used for statistical comparisons. RESULTS: Maximal reductions in systolic and diastolic blood pressures averaging 63 ± 20/29 ± 13 mm Hg were observed approximately two hours after clonidine administration. Decreases in systolic pressure were strongly correlated with baseline systolic pressure. Clonidine produced a significant decrease in heart rate of 11 ± 7 beats/min. No subject required intravenous fluids or vasopressor rescue therapy, or reported spinal headache. CONCLUSIONS: This is the first clinical study in subjects with hypertension that demonstrates significant and profound acute reductions in blood pressure after a single dose of intrathecal clonidine. Future placebo-controlled, dose-escalating studies are warranted to assess the long-term effects of intrathecal clonidine infusion via an implantable drug pump in patients with treatment-resistant hypertension at risk of stroke or myocardial infarction.

Serious complications related to obstetric anesthesia: the serious complication repository project of the Society for Obstetric Anesthesia and Perinatology.

BACKGROUND: Because of the lack of large obstetric anesthesia databases, the incidences of serious complications related to obstetric anesthesia remain unknown. The Society for Obstetric Anesthesia and Perinatology developed the Serious Complication Repository Project to establish the incidence of serious complications related to obstetric anesthesia and to identify risk factors associated with each. METHODS: Serious complications were defined by the Society for Obstetric Anesthesia and Perinatology Research Committee which also coordinated the study. Thirty institutions participated in the approximately 5-yr study period. Data were collected as part of institutional quality assurance and sent to the central project coordinator quarterly. RESULTS: Data were captured on more than 257,000 anesthetics, including 5,000 general anesthetics for cesarean delivery. There were 157 total serious complications reported, 85 of which were anesthesia related. High neuraxial block, respiratory arrest in labor and delivery, and unrecognized spinal catheter were the most frequent complications encountered. A serious complication occurs in approximately 1:3,000 (1:2,443 to 1:3,782) obstetric anesthetics. CONCLUSIONS: The Serious Complication Repository Project establishes the incidence of serious complications in obstetric anesthesia. Because serious complications related to obstetric anesthesia are rare, there were too few complications in each category to identify risk factors associated with each. However, because many of these complications can lead to catastrophic outcomes, it is recommended that the anesthesia provider remains vigilant and be prepared to rapidly diagnose and treat any complication.

Electronic sensor and actuator webs for large-area complex geometry cardiac mapping and therapy.

Curved surfaces, complex geometries, and time-dynamic deformations of the heart create challenges in establishing intimate, nonconstraining interfaces between cardiac structures and medical devices or surgical tools, particularly over large areas. We constructed large area designs for diagnostic and therapeutic stretchable sensor and actuator webs that conformally wrap the epicardium, establishing robust contact without sutures, mechanical fixtures, tapes, or surgical adhesives. These multifunctional web devices exploit open, mesh layouts and mount on thin, bio-resorbable sheets of silk to facilitate handling in a way that yields, after dissolution, exceptionally low mechanical moduli and thicknesses. In vivo studies in rabbit and pig animal models demonstrate the effectiveness of these device webs for measuring and spatially mapping temperature, electrophysiological signals, strain, and physical contact in sheet and balloon-based systems that also have the potential to deliver energy to perform localized tissue ablation.

Nanoparticle based cancer treatment: can delivered dose and biological dose be reliably modeled and quantified?

Essential developments in the reliable and effective use of heat in medicine include: 1) the ability to model energy deposition and the resulting thermal distribution and tissue damage (Arrhenius models) over time in 3D, 2) the development of non-invasive thermometry and imaging for tissue damage monitoring, and 3) the development of clinically relevant algorithms for accurate prediction of the biological effect resulting from a delivered thermal dose in mammalian cells, tissues, and organs. The accuracy and usefulness of this information varies with the type of thermal treatment, sensitivity and accuracy of tissue assessment, and volume, shape, and heterogeneity of the tumor target and normal tissue. That said, without the development of an algorithm that has allowed the comparison and prediction of the effects of hyperthermia in a wide variety of tumor and normal tissues and settings (cumulative equivalent minutes/ CEM), hyperthermia would never have achieved clinical relevance. A new hyperthermia technology, magnetic nanoparticle-based hyperthermia (mNPH), has distinct advantages over the previous techniques: the ability to target the heat to individual cancer cells (with a nontoxic nanoparticle), and to excite the nanoparticles noninvasively with a non-injurious magnetic field, thus sparing associated normal cells and greatly improving the therapeutic ratio. As such, this modality has great potential as a primary and adjuvant cancer therapy. Although the targeted and safe nature of the noninvasive external activation (hysteretic heating) are a tremendous asset, the large number of therapy based variables and the lack of an accurate and useful method for predicting, assessing and quantifying mNP dose and treatment effect is a major obstacle to moving the technology into routine clinical practice. Among other parameters, mNPH will require the accurate determination of specific nanoparticle heating capability, the total nanoparticle content and biodistribution in the target cells/tissue, and an effective and matching alternating magnetic field (AMF) for optimal and safe excitation of the nanoparticles. Our initial studies have shown that appropriately delivered and targeted nanoparticles are capable of achieving effective tumor cytotoxicity at measured thermal doses significantly less than the understood thermal dose values necessary to achieve equivalent treatment effects using conventional heat delivery techniques. Therefore conventional CEM based thermal dose - tissues effect relationships will not hold for mNPH. The goal of this effort is to provide a platform for determining the biological and physical parameters that will be necessary for accurately planning and performing safe and effective mNPH, creating a new, viable primary or adjuvant cancer therapy.

Open-label exploration of an intravenous nalbuphine and naloxone mixture as an analgesic agent following gynecologic surgery.

OBJECTIVE: The purpose of this series was to explore a 12.5:1 fixed-dose ratio of an intravenous nalbuphine and naloxone mixture (NNM) for use in patients following gynecologic surgery. DESIGN AND PATIENTS: Open-label, nonrandomized case series. The first series was a dose-ranging investigation for 12 patients following elective total abdominal hysterectomy or myomectomy. In this series, fentanyl was used for intraoperative analgesia, and patients were assigned to a lower NNM (2.5 mg/0.2 mg) or to a higher NNM (5 mg/0.4 mg) dose group. The second series evaluated the fixed dose of 5 mg nalbuphine/0.4 mg naloxone for four patients undergoing ambulatory gynecologic procedures. In the second series, no opioid agents were administered intraoperatively to eliminate the possibility of mu-opioid reversal by naloxone postoperatively. OUTCOME MEASURES: Pain control was assessed using a Verbal Pain Scale (0-10). Vital signs, side effects, and adverse events were recorded to determine drug safety. RESULTS: In the first series, there were no adverse events; however, each patient required rescue medication (either morphine or fentanyl). In the second series, two of the four patients reported a reduction in pain following drug administration and did not require any further analgesic agents in the 3-hour postoperative period. One patient had an asymptomatic lowering of heart rate after receiving the drug. CONCLUSION: Additional research of the unique combination therapy of nalbuphine and naloxone is warranted to further determine its potential clinical efficacy and safety.

Dural puncture with a 27-gauge Whitacre needle as part of a combined spinal-epidural technique does not improve labor epidural catheter function.

BACKGROUND: This prospective, double-blind, randomized study was designed to examine whether the combined spinal-epidural technique without subarachnoid drug administration improved epidural catheter function when compared with the traditional epidural technique. METHODS: After institutional review board approval and informed consent, 251 healthy laboring parturients were randomly assigned to either group DP (combined spinal-epidural technique with 27-gauge Whitacre needle dural puncture but without subarachnoid drug administration) or group NoDP (traditional epidural technique). Patient-controlled epidural analgesia was initiated with 0.11% bupivacaine and 2 microg/ml fentanyl. Top-up doses in 5-ml increments of 0.25% bupivacaine were administered if needed. Previous power analysis revealed that a sample size of 108 patients/group was needed to show a clinically useful reduction of the catheter manipulation rate from 32% to 15%. RESULTS: In groups DP and NoDP, 107 and 123 evaluable patients, respectively, completed the study. Demographics and outcome variables measured, including epidural catheter manipulation and replacement rate, sacral sparing, unilateral block, number of top-up doses, average hourly epidural drug usage, highest sensory blockade level, and labor analgesia quality, were not different between groups. A subgroup of 18 patients without cerebral spinal fluid return during dural puncture had a higher catheter replacement rate than those of groups DP and NoDP, but it did not reach statistical significance. CONCLUSIONS: Dural puncture with a 27-gauge Whitacre needle without subarachnoid drug administration during combined spinal-epidural labor analgesia did not improve epidural labor analgesia quality or reduce catheter manipulation or replacement rate when compared with a traditional epidural technique.