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.

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.

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.