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Objectives: Although the Affordable Care Act has greatly expanded coverage, the physician workforce has not increased commensurately. Data on wait times, especially among dermatologists who accept Medicaid, are lacking. The objective of this study was to evaluate wait times in dermatology clinics by insurance coverage and chief complaint., Study Design: A "secret shopper" survey was conducted., Methods: Between June and July 2016, 186 dermatology clinics in Michigan were contacted to determine the earliest available appointment for a patient seeking an evaluation of a changing mole, a chronic rash, and botulinum toxin administration., Results: The mean (standard error [SE]) wait time regardless of insurance or chief complaint was 28.8 (1.29) days. Clinics that accept Medicaid had longer wait times (32.9 [2.19] vs 25.4 [1.50] days; P = .024). The mean (SE) wait time for a mole or rash was longer for patients with Medicaid compared with those with private insurance (40.0 [4.08] vs 27.7 [1.54] days; P = .003). The mean (SE) wait time for Medicaid patients compared with patients with private insurance was also longer, even within the same clinic (39.1 [4.11] vs 27.5 [1.57] days; median, 23.5 vs 16.0 days). Patients with Medicaid were able to obtain appointments sooner for botulinum toxin administration (22.5 [2.10] days) compared with evaluation of a mole (40.0 [6.63] days) or rash (40.1 [4.99] days) (P = .004)., Conclusions: Wait times for clinic appointments were longer for patients with Medicaid, especially when requesting an evaluation for a medical dermatologic issue compared with a cosmetic consultation. Delay in medical dermatologic care, especially among Medicaid patients, must be addressed.

Clinical evidence suggests a link between fibrosis in the left atrium (LA) and atrial fibrillation (AF), the most common sustained arrhythmia. Image-derived fibrosis is increasingly used for patient stratification and therapy guidance. However, locations of re-entrant drivers (RDs) sustaining AF are unknown and therapy success rates remain suboptimal. This study used image-derived LA models to explore the dynamics of RD stabilization in fibrotic regions and generate maps of RD locations. LA models with patient-specific geometry and fibrosis distribution were derived from late gadolinium enhanced magnetic resonance imaging of 6 AF patients. In each model, RDs were initiated at multiple locations, and their trajectories were tracked and overlaid on the LA fibrosis distributions to identify the most likely regions where the RDs stabilized. The simulations showed that the RD dynamics were strongly influenced by the amount and spatial distribution of fibrosis. In patients with fibrosis burden greater than 25%, RDs anchored to specific locations near large fibrotic patches. In patients with fibrosis burden below 25%, RDs either moved near small fibrotic patches or anchored to anatomical features. The patient-specific maps of RD locations showed that areas that harboured the RDs were much smaller than the entire fibrotic areas, indicating potential targets for ablation therapy. Ablating the predicted locations and connecting them to the existing pulmonary vein ablation lesions was the most effective in-silico ablation strategy., Competing Interests: The authors have declared that no competing interests exist.

Background: Pectoral nerve blocks (PECs) can reduce intraprocedural anesthetic requirements and postoperative pain. Little is known about the utility of PECs in reducing pain and narcotic use after pacemaker (PM) or implantable cardioverter-defibrillator (ICD) placement in children., Objective: The purpose of this study was to determine whether PECs can decrease postoperative pain and opioid use after PM or ICD placement in children., Methods: A single-center retrospective review of pediatric patients undergoing transvenous PM or ICD placement between 2015 and 2020 was performed. Patients with recent cardiothoracic surgery or neurologic/developmental deficits were excluded. Demographics, procedural variables, postoperative pain, and postoperative opioid usage were compared between patients who had undergone PECs and those who had undergone conventional local anesthetic (Control)., Results: A total of 74 patients underwent PM or ICD placement; 20 patients (27%) underwent PECs. There were no differences between PECs and Control with regard to age, weight, gender, type of device placed, presence of congenital heart disease, type of anesthesia, procedural time, or complication rates. Patients who underwent PECs had lower pain scores at 1, 2, 6, 18, and 24 hours compared to Control. PECs patients had a lower mean cumulative pain score [PECs 1.5 (95% confidence interval [CI] 0.8-2.2) vs Control 3.1 (95% CI 2.7-3.5); P <.001] and lower total opioid use [PECs 6.0 morphine milligram equivalent (MME)/m 2 (95% CI 3.4-8.6) vs Control 15.0 MME/m 2 (95% CI 11.8-18.2); P = .001] over the 24 hours postimplant., Conclusion: PECs reduce postoperative pain scores and lower total opioid usage after ICD or PM placement. PECs should be considered at the time of transvenous device placement in children., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillators (ICDs) are well-established therapies for adult patients with heart failure that have been shown to improve morbidity and mortality. However, the benefits and indications for use in adults with congenital heart disease (ACHD) are less defined with no significant large prospective studies in this population. There are, however, multiple retrospective studies that demonstrate the efficacy of these devices in the ACHD population. These indicate a role for both CRT and ICDs in select patients with ACHD. The clinician and patient must balance the risks and benefits, summarized in complex evidence that reflects the heterogeneity of the ACHD patient group, and apply them in a patient-specific manner to optimize the utility of CRT and ICDs.

Aims: Management strategies for pulmonary atresia with intact ventricular septum are variable and are based on right ventricular morphology and associated abnormalities. Catheter perforation of the pulmonary valve provides an alternative strategy to surgery in the neonatal period. We sought to assess the long-term outcome in terms of survival, re-intervention, and functional ventricular outcome in the setting of a 26-year single-centre experience of low threshold inclusion criteria for percutaneous valvotomy., Methods and Results: Retrospective analysis of patients diagnosed with pulmonary atresia with intact ventricular septum from 1990 to 2016 at a tertiary referral centre, was performed. Of 71 patients, 48 were brought to the catheterisation laboratory for intervention. Catheter valvotomy was successful in 45 patients (94%). Twenty-three patients (51%) also underwent ductus arteriosus stenting. The length of intensive care and hospital stay was significantly shorter, and early re-interventions were significantly reduced in the catheterisation group. There were eight deaths (17%); all within 35 days of the procedure. Of the survivors, only one has required a Fontan circulation. Twenty-eight patients (74%) have undergone biventricular repair and nine patients (24%) have one-and-a-half ventricle circulation. Following successful valvotomy, 80% of patients required further catheter-based or surgical interventions., Conclusions: A low threshold for initial interventional management yielded a high rate of successful biventricular circulations. Although mortality was low in patients who survived the peri-procedural period, the rate of re-intervention remained high in all groups.

Coarctation of the aorta (COA) is suspected prenatally when there is ventricular asymmetry, arterial disproportion, and hypoplasia of the aortic arch/isthmus. The presence of fetal shunts creates difficulty in prenatal confirmation of the diagnosis so serial echocardiography after birth is necessary to confirm or refute the diagnosis. The first neonatal echocardiogram in prenatally suspected cases of COA was assessed for prediction of neonatal COA repair (NCOAR). This included morphological assessment, measurement of the aortic arch and calculation of the distal arch index (DAI = distance between left common carotid and left subclavian artery/diameter of the distal arch). NCOAR was undertaken in 23/60 (38%) cases. Transverse arch, aortic isthmus z-score, and DAI had an area under the receiver operator curve of 0.88 (95% CI 0.77-0.98), 0.86 (95% CI 0.75-0.96), and 0.84 (95% CI 0.74-0.95), respectively for the prediction of NCOAR. Using transverse arch z-score threshold < - 3 gave sensitivity 100%, NPV: 100%, specificity 76%; aortic isthmus z-score  < - 3: NPV 92%, specificity 62% and DAI > 1.4: NPV 88%, specificity 78%. The size of the distal aortic arch in infants with a common origin of the innominate artery and left common carotid artery who did not require COA repair was similar to the NCOAR cases (p = 0.22). The early postnatal assessment of the size and morphology of the aortic arch can assist in risk stratification for development of neonatal COA. The branching pattern of the head/neck vessels impacts on the size of the distal aortic arch adding to the complexity of predicting COA based on vessel size.

Background: Cardiac resynchronization therapy (CRT) studies in pediatric or congenital heart disease patients have shown an improvement in ejection fraction and heart failure symptoms. However, a survival benefit of CRT in this population has not been established. This study aimed to evaluate the impact of CRT upon heart transplant-free survival in pediatric and congenital heart disease patients, using a propensity score-matched (PSM) analysis., Methods: This single-center study compared CRT patients (implant date, 2004-2017) and controls, matched by 1:1 PSM using 21 comprehensive baseline indices for risk stratification. CRT patients were <21 years of age or had congenital heart disease, had systemic ventricular ejection fraction <45%, symptomatic heart failure, and had significant electrical dyssynchrony, all before CRT implant. Controls were screened from nonselective imaging and ECG databases. Controls were retrospectively enrolled when they achieved the same inclusion criteria at an outpatient clinical encounter, within the same time period., Results: Of 133 patients who received CRT during the study period, 84 met all study inclusion criteria. One hundred thirty-three controls met all criteria at an outpatient encounter. Following PSM, 63 matched CRT-control pairs were identified with no significant difference between groups across all baseline indices. Heart transplant or death occurred in 12 (19%) PSM-CRT subjects and 37 (59%) PSM-controls with a median follow-up of 2.7 years (quartiles, 0.8-6.1 years). CRT was associated with markedly reduced risk of heart transplant or death (hazard ratio, 0.24 [95% CI, 0.12-0.46]; P <0.001). There was no CRT procedural mortality and 1 system infection at 54 months post-implant., Conclusions: In pediatric and congenital heart disease patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplant-free survival. Visual Overview: A visual overview is available for this article.

Background: There are currently no published algorithms for calculation of age-dependent QRS duration z-scores. The absence of a standardized measure has limited researchers' abilities to compare ECG measurements of electrical synchrony between subjects of different ages or longitudinally over time., Methods: Four existing studies of normal ECG measurements (total 19,062 subjects) were used to estimate age and sex-dependent means and standard deviations., Results: Weighted means and standard deviations were best estimated by cubic functions to create z-score algorithms., Conclusion: Nomograms and algorithms for QRS duration z-scores may be estimated to compare ECG findings in both children and adults., Competing Interests: Declaration of competing interest H Chubb: no relationships to declare. A Dubin: Medtronic and Abbott: educational support. S Ceresnak: Medtronic and Abbott: educational support. K Motonaga: Medtronic and Abbott: educational support., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Ex-vivo cardiovascular magnetic resonance (CMR) imaging has played an important role in the validation of in-vivo CMR characterization of pathological processes. However, comparison between in-vivo and ex-vivo imaging remains challenging due to shape changes occurring between the two states, which may be non-uniform across the diseased heart. A novel two-step process to facilitate registration between ex-vivo and in-vivo CMR was developed and evaluated in a porcine model of chronic myocardial infarction (MI)., Methods: Seven weeks after ischemia-reperfusion MI, 12 swine underwent in-vivo CMR imaging with late gadolinium enhancement followed by ex-vivo CMR 1 week later. Five animals comprised the control group, in which ex-vivo imaging was undertaken without any support in the LV cavity, 7 animals comprised the experimental group, in which a two-step registration optimization process was undertaken. The first step involved a heart specific flexible 3D printed scaffold generated from in-vivo CMR, which was used to maintain left ventricular (LV) shape during ex-vivo imaging. In the second step, a non-rigid co-registration algorithm was applied to align in-vivo and ex-vivo data. Tissue dimension changes between in-vivo and ex-vivo imaging were compared between the experimental and control group. In the experimental group, tissue compartment volumes and thickness were compared between in-vivo and ex-vivo data before and after non-rigid registration. The effectiveness of the alignment was assessed quantitatively using the DICE similarity coefficient., Results: LV cavity volume changed more in the control group (ratio of cavity volume between ex-vivo and in-vivo imaging in control and experimental group 0.14 vs 0.56, p < 0.0001) and there was a significantly greater change in the short axis dimensions in the control group (ratio of short axis dimensions in control and experimental group 0.38 vs 0.79, p < 0.001). In the experimental group, prior to non-rigid co-registration the LV cavity contracted isotropically in the ex-vivo condition by less than 20% in each dimension. There was a significant proportional change in tissue thickness in the healthy myocardium (change = 29 ± 21%), but not in dense scar (change = - 2 ± 2%, p = 0.034). Following the non-rigid co-registration step of the process, the DICE similarity coefficients for the myocardium, LV cavity and scar were 0.93 (±0.02), 0.89 (±0.01) and 0.77 (±0.07) respectively and the myocardial tissue and LV cavity volumes had a ratio of 1.03 and 1.00 respectively., Conclusions: The pattern of the morphological changes seen between the in-vivo and the ex-vivo LV differs between scar and healthy myocardium. A 3D printed flexible scaffold based on the in-vivo shape of the LV cavity is an effective strategy to minimize morphological changes in the ex-vivo LV. The subsequent non-rigid registration step further improved the co-registration and local comparison between in-vivo and ex-vivo data.

Objective: To determine the present-day approach of pediatric cardiac electrophysiologists to asymptomatic Wolff-Parkinson-White (WPW) pattern and to contrast to both published consensus statements and a similar survey., Study Design: A questionnaire was sent to 266 Pediatric and Congenital Electrophysiology Society physician members in 25 countries; 21 questions from the 2003 survey were repeated, with new questions added regarding risk stratification and decision making., Results: We received 113 responses from 13 countries, with responders having extensive electrophysiology experience (median 15 years [IQR 8.5-25 years]). Only 12 (11%) believed that intermittent pre-excitation and 37 (33%) that sudden loss of pre-excitation on exercise test were sufficient evidence of accessory pathway safety to avoid an invasive electrophysiology study. Optimal weight for electrophysiology study was 20 kg (IQR 18-22.5 kg), and 61% and 58% would then ablate all right-sided or left-sided accessory pathways, respectively, regardless of electrophysiological properties, whereas only 23% would ablate all septal accessory pathways (P < .001). Compared with 2003, respondents were more likely to consider inducible arrhythmia (77% vs 26%, P < .001) as sufficient indication alone for ablation., Conclusions: In the context of recent literature regarding the reliability of risk-stratification tools, most operators are now performing electrophysiology study for asymptomatic Wolff-Parkinson-White regardless of noninvasive findings. Many will then proceed to default ablation of all accessory pathways distant from critical conduction structures., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Multiple cardiac magnetic resonance (CMR)-derived indices of atrial fibrillation (AF) substrate have been shown in isolation to predict long-term outcome following catheter ablation. Left atrial (LA) fibrosis, LA volume, LA ejection fraction (EF), left ventricular ejection fraction (LVEF), LA shape (sphericity) and pulmonary vein anatomy have all been shown to correlate with late AF recurrence. This study aimed to validate and assess the relative contribution of multiple indices in a long-term single-center study., Methods and Results: Eighty-nine patients (53% paroxysmal AF, 73% male) underwent comprehensive CMR study before first-time AF ablation (median follow-up 726 days [IQR: 418-1010 days]). The 3D late gadolinium-enhanced acquisition (1.5T, 1.3 × 1.3 × 2 mm) was quantified for fibrosis; LA volume and sphericity were assessed on manual segmentation at atrial diastole; LAEF and LVEF were quantified on multislice cine imaging. AF recurred in 43 patients (48%) overall (31 at 1 year). In the recurrence group, LA fibrosis was higher (42% vs 29%; hazard ratio [HR]: 1.032; P = .002), left atrial ejection fraction (LAEF) lower (25% vs 34%; HR: 0.063; P = .016) and LVEF lower (57% vs 63%; HR: 0.011; P = .008). LA volume (135 vs 124 mL) and sphericity (0.819 vs 0.822) were similar. Multivariate Cox regression analysis was adjusted for age and sex (Model 1), additionally AF type (Model 2) and combined (Model 3). In Models 1 and 2, LA fibrosis, LAEF, and LVEF were independently associated with outcome, but only LA fibrosis was independent in Model 3 (HR: 1.021; P = .022)., Conclusions: LAEF, LVEF, and LA fibrosis differed significantly in the AF recurrence cohort. However, on combined multivariate analysis only LA fibrosis remained independently associated with outcome., (© 2019 Wiley Periodicals, Inc.)

Aims: Potential advantages of real-time magnetic resonance imaging (MRI)-guided electrophysiology (MR-EP) include contemporaneous three-dimensional substrate assessment at the time of intervention, improved procedural guidance, and ablation lesion assessment. We evaluated a novel real-time MR-EP system to perform endocardial voltage mapping and assessment of delayed conduction in a porcine ischaemia-reperfusion model., Methods and Results: Sites of low voltage and slow conduction identified using the system were registered and compared to regions of late gadolinium enhancement (LGE) on MRI. The Sorensen-Dice similarity coefficient (DSC) between LGE scar maps and voltage maps was computed on a nodal basis. A total of 445 electrograms were recorded in sinus rhythm (range: 30-186) using the MR-EP system including 138 electrograms from LGE regions. Pacing captured at 103 sites; 47 (45.6%) sites had a stimulus-to-QRS (S-QRS) delay of ≥40 ms. Using conventional (0.5-1.5 mV) bipolar voltage thresholds, the sensitivity and specificity of voltage mapping using the MR-EP system to identify MR-derived LGE was 57% and 96%, respectively. Voltage mapping had a better predictive ability in detecting LGE compared to S-QRS measurements using this system (area under curve: 0.907 vs. 0.840). Using an electrical threshold of 1.5 mV to define abnormal myocardium, the total DSC, scar DSC, and normal myocardium DSC between voltage maps and LGE scar maps was 79.0 ± 6.0%, 35.0 ± 10.1%, and 90.4 ± 8.6%, respectively., Conclusion: Low-voltage zones and regions of delayed conduction determined using a real-time MR-EP system are moderately associated with LGE areas identified on MRI., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Exposure to the sun causes premature skin aging, known as photoaging. Clinical features of photoaging vary widely among individuals. In one form, skin appears thin with telangiectasia, and in another form, skin appears thickened with coarse wrinkles. Etiologic, clinical, and therapeutic distinctions among different forms of photoaging remain largely unknown., Objective: To characterize the clinical, histologic, and molecular features of hypertrophic and atrophic photoaging., Methods: In total, 53 individuals were clinically classified as having primarily atrophic or hypertrophic photoaging or neither (controls). Participants' demographic and sun exposure-related lifestyle data were captured by questionnaire. Fifteen clinical features of participants were qualitatively or quantitively scored. Facial biopsies were analyzed for gene expression and histologic characteristics., Results: Actinic and seborrheic keratosis, telangiectasia, and prior incidence of skin cancers were statistically significantly greater and photoaging scale severity, coarse wrinkles, thickness, and sallowness were significantly reduced in atrophic versus hypertrophic groups. Histology also revealed significantly less elastotic material in atrophic photoaging. Gene expression of matrix metalloproteinases and collagens did not differ between the 2 forms of photoaging., Limitations: The study was not designed to identify other possible subtypes of photoaging., Conclusion: Systematic, categorical, and quantitative clinical and histologic assessments distinguish atrophic and hypertrophic photoaging., (Copyright © 2019. Published by Elsevier Inc.)

Biomedical repositories such as the UK Biobank provide increasing access to prospectively collected cardiac imaging, however these data are unlabeled, which creates barriers to their use in supervised machine learning. We develop a weakly supervised deep learning model for classification of aortic valve malformations using up to 4,000 unlabeled cardiac MRI sequences. Instead of requiring highly curated training data, weak supervision relies on noisy heuristics defined by domain experts to programmatically generate large-scale, imperfect training labels. For aortic valve classification, models trained with imperfect labels substantially outperform a supervised model trained on hand-labeled MRIs. In an orthogonal validation experiment using health outcomes data, our model identifies individuals with a 1.8-fold increase in risk of a major adverse cardiac event. This work formalizes a deep learning baseline for aortic valve classification and outlines a general strategy for using weak supervision to train machine learning models using unlabeled medical images at scale.

Purpose of Review: Theoretical benefits of real-time MRI guidance over conventional electrophysiology include contemporaneous 3D substrate assessment and accurate intra-procedural guidance and evaluation of ablation lesions. We review the unique challenges inherent to MRI-guided electrophysiology and how to translate the potential benefits in the treatment of cardiac arrhythmias., Recent Findings: Over the last 5 years, there has been substantial progress, initially in animal models and more recently in clinical studies, to establish methods and develop workflows within the MR environment that resemble those of conventional electrophysiology laboratories. Real-time MRI-guided systems have been used to perform electroanatomic mapping and ablation in patients with atrial flutter, and there is interest in developing the technology to tackle more complex arrhythmias including atrial fibrillation and ventricular tachycardia., Summary: Mainstream adoption of real-time MRI-guided electrophysiology will require demonstration of clinical benefit and will be aided by increased availability of devices suitable for use in the MRI environment., Competing Interests: Conflict of Interest Rahul K. Mukherjee, Henry Chubb, Sébastien Roujol, Reza Razavi and Mark D. O’Neill declare that they have no conflict of interest.

Pulmonary vein isolation (PVI) is a common procedure for the treatment of atrial fibrillation (AF) since the initial trigger for AF frequently originates in the pulmonary veins. A successful isolation produces a continuous lesion (scar) completely encircling the veins that stops activation waves from propagating to the atrial body. Unfortunately, the encircling lesion is often incomplete, becoming a combination of scar and gaps of healthy tissue. These gaps are potential causes of AF recurrence, which requires a redo of the isolation procedure. Late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) is a non-invasive method that may also be used to detect gaps, but it is currently a time-consuming process, prone to high inter-observer variability. In this paper, we present a method to semi-automatically identify and quantify ablation gaps. Gap quantification is performed through minimum path search in a graph where every node is a scar patch and the edges are the geodesic distances between patches. We propose the Relative Gap Measure (RGM) to estimate the percentage of gap around a vein, which is defined as the ratio of the overall gap length and the total length of the path that encircles the vein. Additionally, an advanced version of the RGM has been developed to integrate gap quantification estimates from different scar segmentation techniques into a single figure-of-merit. Population-based statistical and regional analysis of gap distribution was performed using a standardised parcellation of the left atrium. We have evaluated our method on synthetic and clinical data from 50 AF patients who underwent PVI with radiofrequency ablation. The population-based analysis concluded that the left superior PV is more prone to lesion gaps while the left inferior PV tends to have less gaps (p < .05 in both cases), in the processed data. This type of information can be very useful for the optimization and objective assessment of PVI interventions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: The VisiTag module (CARTO3) provides an objective assessment of radiofrequency (RF) ablation parameters. This study aimed to determine the predictive value and optimal VisiTag threshold settings for prediction of gaps in mature atrial scar, as assessed non-invasively using cardiac magnetic resonance (CMR) imaging., Methods: Twenty-four subjects (11 paroxysmal atrial fibrillation) underwent first-time RF ablation with operators blinded to VisiTag data. Three-dimensional late gadolinium enhancement (LGE) CMR scans were performed at 3 months (1.3 × 1.3 × 4 mm 3 ). A survey of UK operators defined the standard VisiTag settings ("Force," 8 g; "Time," 10 seconds; "Percentage Time," 50%; "Range," 3 mm; "Impedance" and "Temperature" "off"). Each ablation procedure was exported 27 times, varying single VisiTag parameters from default values. The presence of gaps in VisiTag markers (18 sectors) was assessed for each export and compared with gaps in CMR enhancement., Results: At default settings, VisiTag gaps were specific (97.5%) but less sensitive (50.4%) for CMR gaps. Sensitivity improved at higher thresholds (89.2% at 20 g, 85.6% at 30 seconds, 88.5% impedance 10 Ω, 92.8% temperature 42°C), but with a lower positive predictive value (PPV) (42.3%, 42.7%, 41.1%, and 37.7%, respectively, vs 90.9% at baseline). "Force" thresholds demonstrated stable PPV from 2 to 8 g (P = 0.24), but a rapid fall at forces more than 10 g. The binomial logistic regression model explained 41.7% of gaps; χ 2 (4), 148; P < 0.0001, correctly classifying 82% of cases (specificity 94.9%, sensitivity 56.8%)., Conclusion: Gaps in VisiTags predict gaps in CMR LGE enhancement with high specificity at default settings. Sensitivity may be improved using more stringent thresholds but at the potential cost of unnecessary ablation, particularly when a force more than 10 g is stipulated., (© 2018 Wiley Periodicals, Inc.)

Introduction: Atrial fibrillation (AF) is a widespread cardiac arrhythmia that commonly affects the left atrium (LA), causing it to quiver instead of contracting effectively. This behavior is triggered by abnormal electrical impulses at a specific site in the atrial wall. Catheter ablation (CA) treatment consists of isolating this driver site by burning the surrounding tissue to restore sinus rhythm (SR). However, evidence suggests that CA can concur to the formation of blood clots by promoting coagulation near the heat source and in regions with low flow velocity and blood stagnation. Methods: A patient-specific modeling workflow was created and applied to simulate thermal-fluid dynamics in two patients pre- and post-CA. Each model was personalized based on pre- and post-CA imaging datasets. The wall motion and anatomy were derived from SSFP Cine MRI data, while the trans-valvular flow was based on Doppler ultrasound data. The temperature distribution in the blood was modeled using a modified Pennes bioheat equation implemented in a finite-element based Navier-Stokes solver. Blood particles were also classified based on their residence time in the LA using a particle-tracking algorithm. Results: SR simulations showed multiple short-lived vortices with an average blood velocity of 0.2-0.22 m/s. In contrast, AF patients presented a slower vortex and stagnant flow in the LA appendage, with the average blood velocity reduced to 0.08-0.14 m/s. Restoration of SR also increased the blood kinetic energy and the viscous dissipation due to the presence of multiple vortices. Particle tracking showed a dramatic decrease in the percentage of blood remaining in the LA for longer than one cycle after CA (65.9 vs. 43.3% in patient A and 62.2 vs. 54.8% in patient B). Maximum temperatures of 76° and 58°C were observed when CA was performed near the appendage and in a pulmonary vein, respectively. Conclusion: This computational study presents novel models to elucidate relations between catheter temperature, patient-specific atrial anatomy and blood velocity, and predict how they change from SR to AF. The models can quantify blood flow in critical regions, including residence times and temperature distribution for different catheter positions, providing a basis for quantifying stroke risks.

Aims: Conducting gaps in lesion sets are a major reason for failure of ablation procedures. Voltage mapping and pace-capture have been proposed for intra-procedural identification of gaps. We aimed to compare gap size measured acutely and chronically post-ablation to macroscopic gap size in a porcine model., Methods and Results: Intercaval linear ablation was performed in eight Göttingen minipigs with a deliberate gap of ∼5 mm left in the ablation line. Gap size was measured by interpolating ablation contact force values between ablation tags and thresholding at a low force cut-off of 5 g. Bipolar voltage mapping and pace-capture mapping along the length of the line were performed immediately, and at 2 months, post-ablation. Animals were euthanized and gap sizes were measured macroscopically. Voltage thresholds to define scar were determined by receiver operating characteristic analysis as <0.56 mV (acutely) and <0.62 mV (chronically). Taking the macroscopic gap size as gold standard, error in gap measurements were determined for voltage, pace-capture, and ablation contact force maps. All modalities overestimated chronic gap size, by 1.4 ± 2.0 mm (ablation contact force map), 5.1 ± 3.4 mm (pace-capture), and 9.5 ± 3.8 mm (voltage mapping). Error on ablation contact force map gap measurements were significantly less than for voltage mapping (P = 0.003, Tukey's multiple comparisons test). Chronically, voltage mapping and pace-capture mapping overestimated macroscopic gap size by 11.9 ± 3.7 and 9.8 ± 3.5 mm, respectively., Conclusion: Bipolar voltage and pace-capture mapping overestimate the size of chronic gap formation in linear ablation lesions. The most accurate estimation of chronic gap size was achieved by analysis of catheter-myocardium contact force during ablation.

Aims: Magnetic resonance imaging (MRI) is the gold standard for defining myocardial substrate in 3D and can be used to guide ventricular tachycardia ablation. We describe the feasibility of using a prototype magnetic resonance-guided electrophysiology (MR-EP) system in a pre-clinical model to perform real-time MRI-guided epicardial mapping, ablation, and lesion imaging with active catheter tracking., Methods and Results: Experiments were performed in vivo in pigs (n = 6) using an MR-EP guidance system research prototype (Siemens Healthcare) with an irrigated ablation catheter (Vision-MR, Imricor) and a dedicated electrophysiology recording system (Advantage-MR, Imricor). Following epicardial access, local activation and voltage maps were acquired, and targeted radiofrequency (RF) ablation lesions were delivered. Ablation lesions were visualized in real time during RF delivery using MR-thermometry and dosimetry. Hyper-acute and acute assessment of ablation lesions was also performed using native T1 mapping and late-gadolinium enhancement (LGE), respectively. High-quality epicardial bipolar electrograms were recorded with a signal-to-noise ratio of greater than 10:1 for a signal of 1.5 mV. During epicardial ablation, localized temperature elevation could be visualized with a maximum temperature rise of 35 °C within 2 mm of the catheter tip relative to remote myocardium. Decreased native T1 times were observed (882 ± 107 ms) in the lesion core 3-5 min after lesion delivery and relative location of lesions matched well to LGE. There was a good correlation between ablation lesion site on the iCMR platform and autopsy., Conclusion: The MR-EP system was able to successfully acquire epicardial voltage and activation maps in swine, deliver, and visualize ablation lesions, demonstrating feasibility for intraprocedural guidance and real-time assessment of ablation injury.

Diagnostic and interventional cardiac catheterization is routinely used in the diagnosis and treatment of congenital heart disease. There are well-established concerns regarding the risk of radiation exposure to patients and staff, particularly in children given the cumulative effects of repeat exposure. Magnetic resonance imaging (MRI) offers the advantage of being able to provide better soft tissue visualization, tissue characterization, and quantification of ventricular volumes and vascular flow. Initial work using MRI catheterization employed fusion of x-ray and MRI techniques, with x-ray fluoroscopy to guide catheter placement and subsequent MRI assessment for anatomical and hemodynamic assessment. Image overlay of 3D previously acquired MRI datasets with live fluoroscopic imaging has also been used to guide catheter procedures.Hybrid x-ray and MRI-guided catheterization paved the way for clinical application and validation of this technique in the assessment of pulmonary vascular resistance and pharmacological stress studies. Purely MRI-guided catheterization also proved possible with passive catheter tracking. First-in-man MRI-guided cardiac catheter interventions were possible due to the development of MRI-compatible guidewires, but halted due to guidewire limitations.More recent developments in passive and active catheter tracking have led to improved visualization of catheters for MRI-guided catheterization. Improvements in hardware and software have also increased image quality and scanning times with better interactive tools for the operator in the MRI catheter suite to navigate through the anatomy as required in real time. This has expanded to MRI-guided electrophysiology studies and radiofrequency ablation in humans. Animal studies show promise for the utility of MRI-guided interventional catheterization. Ongoing investment and development of MRI-compatible guidewires will pave the way for MRI-guided diagnostic and interventional catheterization coming into the mainstream.

Background: Cardiovascular magnetic resonance (CMR) imaging may be used to visualize post-ablation atrial scar (PAAS), and three-dimensional late gadolinium enhancement (3D LGE) is the most widely employed technique for imaging of chronic scar. Detection of PAAS provides a unique non-invasive insight into the effects of the ablation and may help guide further ablation procedures. However, there is evidence that PAAS is often not detected by CMR, implying a significant sensitivity problem, and imaging parameters vary between leading centres. Therefore, there is a need to establish the optimal imaging parameters to detect PAAS., Methods: Forty subjects undergoing their first pulmonary vein isolation procedure for AF had detailed CMR assessment of atrial scar: one scan pre-ablation, and two scans post-ablation at 3 months (separated by 48 h). Each scan session included ECG- and respiratory-navigated 3D LGE acquisition at 10, 20 and 30 min post injection of a gadolinium-based contrast agent (GBCA). The first post-procedural scan was performed on a 1.5 T scanner with standard acquisition parameters, including double dose (0.2 mmol/kg) Gadovist and 4 mm slice thickness. Ten patients subsequently underwent identical scan as controls, and the other 30 underwent imaging with a reduced, single, dose GBCA (n = 10), half slice thickness (n = 10) or on a 3 T scanner (n = 10). Apparent signal-to-noise (aSNR), contrast-to-noise (aCNR) and imaging quality (Likert Scale, 3 independent observers) were assessed. PAAS location and area (%PAAS scar) were assessed following manual segmentation. Atrial shells with standardised %PAAS at each timepoint were then compared to ablation lesion locations to assess quality of scar delineation., Results: A total of 271 3D acquisitions (out of maximum 280, 96.7%) were acquired. Likert scale of imaging quality had high interobserver and intraobserver intraclass correlation coefficients (0.89 and 0.96 respectively), and showed lower overall imaging quality on 3 T and at half-slice thickness. aCNR, and quality of scar delineation increased significantly with time. aCNR was higher with reduced, single, dose of GBCA (p = 0.005)., Conclusion: 3D LGE CMR atrial scar imaging, as assessed qualitatively and quantitatively, improves with time from GBCA administration, with some indices continuing to improve from 20 to 30 min. Imaging should be performed at least 20 min post-GBCA injection, and a single dose of contrast should be considered., Trial Registration: Trial registry- United Kingdom National Research Ethics Service 08/H0802/68 - 30th September 2008.

Background: The Lesion Index (LSI) is a proprietary algorithm from Abbott Medical combining contact force, radiofrequency application duration, and radiofrequency current. It can be displayed during ablation with the TactiCath contact force catheter. The LSI Index was designed to provide real-time lesion formation feedback and is hypothesized to estimate the lesion diameter., Methods and Results: Before ablation, animals underwent cardiac computed tomography to assess atrial tissue thickness. Ablation lines (n=2-3 per animal) were created in the right atrium of 7 Göttingen mini pigs with point lesions (25 W). Within each line of ablation, the catheter tip was moved a prescribed distance (D/mm) according to 1 of 3 strategies: D=LSI+0 mm; D=LSI+2 mm; or D=LSI+4 mm. Two weeks after ablation, serial sections of targeted atrial tissue were examined histologically to identify gaps in transmural ablation. LSI-guided lines had a lower incidence of histological gaps (4 gaps in 69 catheter moves, 5.8%) than LSI+2 mm lines (7 gaps in 33 catheter moves, 21.2%) and LSI+4 mm lines (15 gaps in 23 catheter moves, 65.2%, P <0.05 versus D=LSI). ΔLSI was calculated retrospectively as the distance between 2 adjacent lesions above the mean LSI of the 2 lesions. ΔLSI values of ≤1.5 were associated with no gaps in transmural ablation., Conclusions: In this model of chronic atrial ablation, delivery of uninterrupted transmural linear lesions may be facilitated by using LSI to guide catheter movement. When ΔLSI between adjacent lesions is ≤1.5 mm, no gaps in atrial linear lesions should be expected., (© 2018 The Authors.)

Background: Cardiovascular magnetic resonance (CMR) imaging has been used to visualise post-ablation atrial scar (PAAS), generally employing a three-dimensional (3D) late gadolinium enhancement (LGE) technique. However the reproducibility of PAAS imaging has not been determined. This cross-over study is the first to investigate the reproducibility of the technique, crucial for both future research design and clinical implementation., Methods: Forty subjects undergoing first time ablation for atrial fibrillation (AF) had detailed CMR assessment of PAAS. Following baseline pre-ablation scan, two scans (separated by 48 h) were performed at three months post-ablation. Each scan session included 3D LGE acquisition at 10, 20 and 30 min post administration of gadolinium-based contrast agent (GBCA). Subjects were allocated at second scan post-ablation to identical imaging parameters ('Repro', n = 10), 3 T scanner ('3 T', n = 10), half-slice thickness ('Half-slice', n = 10) or half GBCA dose ('Half-gad', n = 10). PAAS was compared to baseline scar and then reproducibility was assessed for two measures of thresholded scar (% left atrial (LA) occupied by PAAS (%LA PAAS) and Pulmonary Vein Encirclement (PVE)), and then four measures of non-thresholded scar (point-by-point assessment of PAAS, four normalisation methods). Thresholded measures of PAAS were evaluated against procedural outcome (AF recurrence)., Results: A total of 271 3D acquisitions (out of maximum 280, 96.7%) were acquired. At 20 and 30 min, inter-scan reproducibility was good to excellent (coefficient of variation at 20 min and 30 min: %LA PAAS 0.41 and 0.20; PVE 0.13 and 0.04 respectively for 'Repro' group). Changes in imaging parameters, especially reduced GBCA dose, reduced inter-scan reproducibility, but for most measures remained good to excellent (ICC for %LA PAAS 0.454-0.825, PVE 0.618-0.809 at 30 min). For non-thresholded scar, highest reproducibility was observed using blood pool z-score normalisation technique: inter-scan ICC 0.759 (absolute agreement, 'Repro' group). There was no significant relationship between indices of PAAS and AF recurrence., Conclusion: PAAS imaging is a reproducible finding. Imaging should be performed at least 20 min post-GBCA injection, and a blood pool z-score should be considered for normalisation of signal intensities. The clinical implications of these findings remain to be established in the absence of a simple correlation with arrhythmia outcome., Trial Registration: United Kingdom National Research Ethics Service 08/H0802/68 - 30th September 2008.

Aims: Local activation time (LAT) mapping forms the cornerstone of atrial tachycardia diagnosis. Although anatomic and positional accuracy of electroanatomic mapping (EAM) systems have been validated, the effect of electrode sampling density on LAT map reconstruction is not known. Here, we study the effect of chamber geometry and activation complexity on optimal LAT sampling density using a combined in silico and in vivo approach., Methods and Results: In vivo 21 atrial tachycardia maps were studied in three groups: (1) focal activation, (2) macro-re-entry, and (3) localized re-entry. In silico activation was simulated on a 4×4cm atrial monolayer, sampled randomly at 0.25-10 points/cm2 and used to re-interpolate LAT maps. Activation patterns were studied in the geometrically simple porcine right atrium (RA) and complex human left atrium (LA). Activation complexity was introduced into the porcine RA by incomplete inter-caval linear ablation. In all cases, optimal sampling density was defined as the highest density resulting in minimal further error reduction in the re-interpolated maps. Optimal sampling densities for LA tachycardias were 0.67 ± 0.17 points/cm2 (focal activation), 1.05 ± 0.32 points/cm2 (macro-re-entry) and 1.23 ± 0.26 points/cm2 (localized re-entry), P = 0.0031. Increasing activation complexity was associated with increased optimal sampling density both in silico (focal activation 1.09 ± 0.14 points/cm2; re-entry 1.44 ± 0.49 points/cm2; spiral-wave 1.50 ± 0.34 points/cm2, P < 0.0001) and in vivo (porcine RA pre-ablation 0.45 ± 0.13 vs. post-ablation 0.78 ± 0.17 points/cm2, P = 0.0008). Increasing chamber geometry was also associated with increased optimal sampling density (0.61 ± 0.22 points/cm2 vs. 1.0 ± 0.34 points/cm2, P = 0.0015)., Conclusion: Optimal sampling densities can be identified to maximize diagnostic yield of LAT maps. Greater sampling density is required to correctly reveal complex activation and represent activation across complex geometries. Overall, the optimal sampling density for LAT map interpolation defined in this study was ∼1.0-1.5 points/cm2., (Published on behalf of the European Society of Cardiology)

Systemic arterial hypertension predisposes children to cardiovascular risk in childhood and adult life. Despite extensive study of left ventricular (LV) hypertrophy, detailed 3-dimensional strain analysis of cardiac function in hypertensive children has not been reported. The aim of this study was to evaluate LV mechanics (strain, twist, and torsion) in young patients with hypertension compared with a healthy control group and assess factors associated with functional measurements. Sixty-three patients (26 hypertension and 37 normotensive) were enrolled (mean age, 14.3 and 11.4 years; 54% men and 41% men, respectively). All children underwent clinical evaluation and echocardiographic examination, including 3-dimensional strain. There was no difference in LV volumes and ejection fraction between the groups. Myocardial deformation was significantly reduced in those with hypertension compared with controls. For hypertensive and normotensive groups, respectively, global longitudinal strain was -15.1±2.3 versus -18.5±1.9 ( P <0.0001), global circumferential strain -15.2±3 versus -19.9±3.1 (<0.0001), global radial strain +44.0±11.3 versus 63.4±10.5 ( P <0.0001), and global 3-dimensional strain -26.1±3.8 versus -31.5±3.8 ( P <0.0001). Basal clockwise rotation, apical counterclockwise rotation, twist, and torsion were not significantly different. After multivariate regression analyses blood pressure, body mass index and LV mass maintained a significant relationship with measures of LV strain. Similar ventricular volumes and ejection fraction were observed in hypertensive and normotensive children, but children with hypertension had significantly lower strain indices. Whether reduced strain might predict future cardiovascular risk merits further longitudinal study., (© 2017 American Heart Association, Inc.)

Cardiac magnetic resonance imaging (MRI) is appealing to guide complex cardiac procedures because it is ionizing radiation-free and offers flexible soft-tissue contrast. Interventional cardiac MR promises to improve existing procedures and enable new ones for complex arrhythmias, as well as congenital and structural heart disease. Guiding invasive procedures demands faster image acquisition, reconstruction and analysis, as well as intuitive intraprocedural display of imaging data. Standard cardiac MR techniques such as 3D anatomical imaging, cardiac function and flow, parameter mapping, and late-gadolinium enhancement can be used to gather valuable clinical data at various procedural stages. Rapid intraprocedural image analysis can extract and highlight critical information about interventional targets and outcomes. In some cases, real-time interactive imaging is used to provide a continuous stream of images displayed to interventionalists for dynamic device navigation. Alternatively, devices are navigated relative to a roadmap of major cardiac structures generated through fast segmentation and registration. Interventional devices can be visualized and tracked throughout a procedure with specialized imaging methods. In a clinical setting, advanced imaging must be integrated with other clinical tools and patient data. In order to perform these complex procedures, interventional cardiac MR relies on customized equipment, such as interactive imaging environments, in-room image display, audio communication, hemodynamic monitoring and recording systems, and electroanatomical mapping and ablation systems. Operating in this sophisticated environment requires coordination and planning. This review provides an overview of the imaging technology used in MRI-guided cardiac interventions. Specifically, this review outlines clinical targets, standard image acquisition and analysis tools, and the integration of these tools into clinical workflow., Level of Evidence: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:935-950., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: Left atrial arrhythmia substrate assessment can involve multiple imaging and electrical modalities, but visual analysis of data on 3D surfaces is time-consuming and suffers from limited reproducibility. Unfold maps (e.g., the left ventricular bull's eye plot) allow 2D visualization, facilitate multimodal data representation, and provide a common reference space for inter-subject comparison. The aim of this work is to develop a method for automatic representation of multimodal information on a left atrial standardized unfold map (LA-SUM)., Methods: The LA-SUM technique was developed and validated using 18 electroanatomic mapping (EAM) LA geometries before being applied to ten cardiac magnetic resonance/EAM paired geometries. The LA-SUM was defined as an unfold template of an average LA mesh, and registration of clinical data to this mesh facilitated creation of new LA-SUMs by surface parameterization., Results: The LA-SUM represents 24 LA regions on a flattened surface. Intra-observer variability of LA-SUMs for both EAM and CMR datasets was minimal; root-mean square difference of 0.008 ± 0.010 and 0.007 ± 0.005 ms (local activation time maps), 0.068 ± 0.063 gs (force-time integral maps), and 0.031 ± 0.026 (CMR LGE signal intensity maps). Following validation, LA-SUMs were used for automatic quantification of post-ablation scar formation using CMR imaging, demonstrating a weak but significant relationship between ablation force-time integral and scar coverage (R 2  = 0.18, P < 0.0001)., Conclusions: The proposed LA-SUM displays an integrated unfold map for multimodal information. The method is applicable to any LA surface, including those derived from imaging and EAM systems. The LA-SUM would facilitate standardization of future research studies involving segmental analysis of the LA.

Objectives: This study sought to characterize direction-dependent and coupling interval-dependent changes in left atrial conduction and electrogram morphology in uniformly classified patients with paroxysmal atrial fibrillation (AF) and normal bipolar voltage mapping., Background: Although AF classifications are based on arrhythmia duration, the clinical course, and treatment response vary between patients within these groups. Electrophysiological mechanisms responsible for this variability are incompletely described., Methods: Intracardiac contact mapping during incremental atrial pacing was used to characterize atrial conduction, activation dispersion, and electrogram morphology in 15 consecutive paroxysmal AF patients undergoing first-time pulmonary vein isolation. Outcome measures were vulnerability to AF induction at electrophysiology study and 2-year follow-up for arrhythmia recurrence., Results: Conduction delay showed a bimodal distribution, occurring at either long (high right atrium pacing: 326 ± 13 ms; coronary sinus pacing: 319 ± 16 ms) or short (high right atrium pacing: 275 ± 11 ms; coronary sinus pacing: 271 ± 11 ms) extrastimulus coupling intervals. Arrhythmia recurrence was found only in patients with conduction delay at long extrastimulus coupling intervals, and patients with inducible AF were characterized by increased activation dispersion (activation dispersion time: 168 ± 29 ms vs. 136 ± 11 ms). Electrogram voltage and duration varied throughout the left atrium, between patients, and with pacing site but were not correlated with AF vulnerability or arrhythmia recurrence., Conclusions: Within the single clinical entity of paroxysmal AF, incremental atrial pacing identified a spectrum of activation patterns correlating with AF vulnerability and arrhythmia recurrence. In contrast, electrogram morphology (characterized by electrogram voltage and duration) was highly variable and not associated with AF vulnerability or recurrence. An improved understanding of the electrical phenotype in AF could lead to improved mechanistic classifications.

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that affects tumorigenesis by epigenetic gene silencing. Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that has a high risk of disease progression with nodal and distant metastases. Here, we evaluated EZH2 expression by immunohistochemistry in a cohort of 85 MCC tumors (29 primary tumors, 41 lymph node metastases, 13 in-transit metastases, and 2 distant metastases) with clinical follow-up. We show strong/moderate EZH2 expression in 54% of tumors. Importantly, weak expression of EZH2 in the primary tumor, but not nodal metastases, correlated with improved prognosis compared to moderate/strong EZH2 expression (5-year MCC-specific survival of 68% versus 22%, respectively, P=.024). In addition, EZH2 was expressed at higher levels in nodal metastases compared to primary tumors (P=.005). Our data demonstrate that EZH2 has prognostic value and may play an oncogenic role in MCC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Knowledge of atrial wall thickness (AWT) has the potential to provide important information for patient stratification and the planning of interventions in atrial arrhythmias. To date, information about AWT has only been acquired in post-mortem or poor-contrast computed tomography (CT) studies, providing limited coverage and highly variable estimates of AWT. We present a novel contrast agent-free MRI sequence for imaging AWT and use it to create personalized AWT maps and a biatrial atlas. A novel black-blood phase-sensitive inversion recovery protocol was used to image ten volunteers and, as proof of concept, two atrial fibrillation patients. Both atria were manually segmented to create subject-specific AWT maps using an average of nearest neighbors approach. These were then registered non-linearly to generate an AWT atlas. AWT was 2.4 ± 0.7 and 2.7 ± 0.7 mm in the left and right atria, respectively, in good agreement with post-mortem and CT data, where available. AWT was 2.6 ± 0.7 mm in the left atrium of a patient without structural heart disease, similar to that of volunteers. In a patient with structural heart disease, the AWT was increased to 3.1 ± 1.3 mm. We successfully designed an MRI protocol to non-invasively measure AWT and create the first whole-atria AWT atlas. The atlas can be used as a reference to study alterations in thickness caused by atrial pathology. The protocol can be used to acquire personalized AWT maps in a clinical setting and assist in the treatment of atrial arrhythmias.

MR-guidance of electrophysiological (EP) procedures offers the potential for enhanced arrhythmia substrate assessment, improved procedural guidance and real-time assessment of ablation lesion formation. Accurate device tracking techniques, using both active and passive methods, have been developed to offer an interface similar to electroanatomic mapping platforms, and MR-compatible EP equipment continues to be developed. Progress to clinical implementation of these technically complex fields has been relatively slow over the last 10 years, but recent developments have led to successful clinical experience. However, further advances, particularly in harnessing the full imaging potential of CMR, are required to realise the mainstream adoption of this powerful guidance modality., Competing Interests: Disclosure: The authors have no conflict of interest to declare.

Objective: Computational models represent a novel framework for understanding the mechanisms behind atrial fibrillation (AF) and offer a pathway for personalizing and optimizing treatment. The characterization of local electrophysiological properties across the atria during procedures remains a challenge. The aim of this work is to characterize the regional properties of the human atrium from multielectrode catheter measurements., Methods: We propose a novel method that characterizes regional electrophysiology properties by fitting parameters of an ionic model to conduction velocity and effective refractory period restitution curves obtained by a s 1 -s 2 pacing protocol applied through a multielectrode catheter. Using an in-silico dataset we demonstrate that the fitting method can constrain parameters with a mean error of 21.9 ± 16.1% and can replicate conduction velocity and effective refractory curves not used in the original fitting with a relative error of 4.4 ± 6.9%., Results: We demonstrate this parameter estimation approach on five clinical datasets recorded from AF patients. Recordings and parametrization took approx. 5 and 6 min, respectively. Models fitted restitution curves with an error of ~ 5% and identify a unique parameter set. Tissue properties were predicted using a two-dimensional atrial tissue sheet model. Spiral wave stability in each case was predicted using tissue simulations, identifying distinct stable (2/5), meandering and breaking up (2/5), and unstable self-terminating (1/5) spiral tip patterns for different cases., Conclusion and Significance: We have developed and demonstrated a robust and rapid approach for personalizing local ionic models from a clinically tractable.

Objectives: This study sought to develop an actively tracked cardiac magnetic resonance-guided electrophysiology (CMR-EP) system and perform first-in-human clinical ablation procedures., Background: CMR-EP offers high-resolution anatomy, arrhythmia substrate, and ablation lesion visualization in the absence of ionizing radiation. Implementation of active tracking, where catheter position is continuously transmitted in a manner analogous to electroanatomic mapping (EAM), is crucial for CMR-EP to take the step from theoretical technology to practical clinical tool., Methods: The setup integrated a clinical 1.5-T scanner, an EP recording and ablation system, and a real-time image guidance platform with components undergoing ex vivo validation. The full system was assessed using a preclinical study (5 pigs), including mapping and ablation with histological validation. For the clinical study, 10 human subjects with typical atrial flutter (age 62 ± 15 years) underwent MR-guided cavotricuspid isthmus (CTI) ablation., Results: The components of the CMR-EP system were safe (magnetically induced torque, radiofrequency heating) and effective in the CMR environment (location precision). Targeted radiofrequency ablation was performed in all animals and 9 (90%) humans. Seven patients had CTI ablation completed using CMR guidance alone; 2 patients required completion under fluoroscopy, with 2 late flutter recurrences. Acute and chronic CMR imaging demonstrated efficacious lesion formation, verified with histology in animals. Anatomic shape of the CTI was an independent predictor of procedural success., Conclusions: CMR-EP using active catheter tracking is safe and feasible. The CMR-EP setup provides an effective workflow and has the potential to change the way in which ablation procedures may be performed., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Metastasis of cutaneous squamous cell carcinoma (SCC) to the nodal basin is associated with a poor prognosis. The role of sentinel lymph node biopsy (SLNB) for regional staging in patients diagnosed with SCC is unclear., Objective: To evaluate a single institution's experience with use of SLNB for regional staging of SCC on the head and neck., Design, Setting, and Participants: A retrospective review of 53 patients who were diagnosed with SCC on the head and neck, at high risk for nodal metastasis based on National Comprehensive Cancer Network (NCCN) risk factors, and treated with wide local excision (WLE) and SLNB from December 1, 2010, through January 30, 2015, in a single academic referral center was performed. The follow-up period ended November 5, 2015. Sentinel lymph node biopsy paraffin blocks were retrieved and processed retrospectively with serial sectioning and immunohistochemical analysis (IHC) in cases with nodal recurrence following a negative SLNB., Main Outcomes and Measures: Sentinel node (SN) identification rate, SLNB positivity rate, local recurrence, regional nodal recurrence, and distant recurrence., Results: In 53 patients with 54 tumors the SN identification rate was 94%. The SLNB positivity rate was 11.3%. On more thorough tissue processing and IHC, metastatic SCC was identified in 2 of 5 (40%) cases previously deemed negative. After reclassification of these cases, the adjusted SLNB positivity rate was 15.1%. The adjusted rate of false omission was 7.1% (95% CI, 2%-19%). Nodal disease developed in 20.8% overall. Angiolymphatic invasion (Cohen d, 3.52; 95% CI, 1.83-5.21), perineural invasion (Cohen d, 0.81; 95% CI, 0.09-1.52), and clinical size (Cohen d, 0.83; 95% CI, 0.05-1.63) were associated with the presence of nodal disease., Conclusions and Relevance: Rigorous study of SLNB for cutaneous SCC incorporating prospectively-collected comprehensive data sets based on standardized treatment algorithms is justified with potential to modify clinical practice. Our study demonstrates the critical importance of serial sectioning and IHC of the SLNB specimen for accurate diagnosis. Use of the NCCN guidelines may facilitate identification of patients with SCC at high risk for nodal metastasis.

Changes in the structure and electrical behaviour of the left atrium are known to occur with conditions that predispose to atrial fibrillation (AF) and in response to prolonged periods of AF. We review the evidence that changes in myocardial thickness in the left atrium are an important part of this pathological remodelling process. Autopsy studies have demonstrated changes in the thickness of the atrial wall between patients with different clinical histories. Comparison of the reported tissue dimensions from pathological studies provides an indication of normal ranges for atrial wall thickness. Imaging studies, most commonly done using cardiac computed tomography, have demonstrated that these changes may be identified non-invasively. Experimental evidence using isolated tissue preparations, animal models of AF, and computer simulations proves that the three-dimensional tissue structure will be an important determinant of the electrical behaviour of atrial tissue. Accurately identifying the thickness of the atrial may have an important role in the non-invasive assessment of atrial structure. In combination with atrial tissue characterization, a comprehensive assessment of the atrial dimensions may allow prediction of atrial electrophysiological behaviour and in the future, guide radiofrequency delivery in regions based on their tissue thickness., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Introduction: The genesis of atrial fibrillation (AF) and success of AF ablation therapy have been strongly linked with atrial fibrosis. Increasing evidence suggests that patient-specific distributions of fibrosis may determine the locations of electrical drivers (rotors) sustaining AF, but the underlying mechanisms are incompletely understood. This study aims to elucidate a missing mechanistic link between patient-specific fibrosis distributions and AF drivers. Methods: 3D atrial models integrated human atrial geometry, rule-based fiber orientation, region-specific electrophysiology, and AF-induced ionic remodeling. A novel detailed model for an atrial fibroblast was developed, and effects of myocyte-fibroblast (M-F) coupling were explored at single-cell, 1D tissue and 3D atria levels. Left atrial LGE MRI datasets from 3 chronic AF patients were segmented to provide the patient-specific distributions of fibrosis. The data was non-linearly registered and mapped to the 3D atria model. Six distinctive fibrosis levels (0-healthy tissue, 5-dense fibrosis) were identified based on LGE MRI intensity and modeled as progressively increasing M-F coupling and decreasing atrial tissue coupling. Uniform 3D atrial model with diffuse (level 2) fibrosis was considered for comparison. Results: In single cells and tissue, the largest effect of atrial M-F coupling was on the myocyte resting membrane potential, leading to partial inactivation of sodium current and reduction of conduction velocity (CV). In the 3D atria, further to the M-F coupling, effects of fibrosis on tissue coupling greatly reduce atrial CV. AF was initiated by fast pacing in each 3D model with either uniform or patient-specific fibrosis. High variation in fibrosis distributions between the models resulted in varying complexity of AF, with several drivers emerging. In the diffuse fibrosis models, waves randomly meandered through the atria, whereas in each the patient-specific models, rotors stabilized in fibrotic regions. The rotors propagated slowly around the border zones of patchy fibrosis (levels 3-4), failing to spread into inner areas of dense fibrosis. Conclusion: Rotors stabilize in the border zones of patchy fibrosis in 3D atria, where slow conduction enable the development of circuits within relatively small regions. Our results can provide a mechanistic explanation for the clinical efficacy of ablation around fibrotic regions.

Background: Perioral wrinkling is commonly reported among older adults, but its objective evaluation and causes remain poorly understood., Objective: We sought to develop a photonumeric scale for perioral wrinkling and to elucidate contributory lifestyle factors., Methods: In this cross-sectional study, we recruited participants for facial photographs and a survey. A gender-specific photonumeric scale for perioral wrinkling was developed and used by 3 graders to evaluate participant photographs. Scores and survey responses were used to create a multiple regression model to predict perioral wrinkling., Results: In all, 143 participants aged 21 to 91 years were enrolled. Intraclass correlation coefficient values for interrater and intrarater reliability were high (>0.8) across 2 trials and 3 graders. A multiple regression model for prediction of perioral wrinkling severity included age, gender, and years of smoking as variables., Limitations: The study was limited by sample size and a predominantly Caucasian study population., Conclusion: We created a photonumeric scale that accounts for gender differences in perioral wrinkling and highlighted contributory variables to photoaging in this anatomical location., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Device therapy in the complex congenital heart disease (CHD) population is a challenging field. There is a myriad of devices available, but none designed specifically for the CHD patient group, and a scarcity of prospective studies to guide best practice. Baseline cardiac anatomy, prior surgical and interventional procedures, existing tachyarrhythmias and the requirement for future intervention all play a substantial role in decision making. For both pacing systems and implantable cardioverter defibrillators, numerous factors impact on the merits of system location (endovascular versus non-endovascular), lead positioning, device selection and device programming. For those with Fontan circulation and following the atrial switch procedure there are also very specific considerations regarding access and potential complications. This review discusses the published guidelines, device indications and the best available evidence for guidance of device implantation in the complex CHD population.

Objective: Selection of fetuses with aortic stenosis (AS) for prenatal intervention has been influenced by published scoring systems. This study aimed to test these scoring systems by retrospective application to consecutive cases of fetal AS., Methods: Retrospective analysis of the echocardiographic findings of 31 consecutive fetuses with AS evaluated at a tertiary fetal cardiology centre. Published 'eHLHS' scores and threshold scores were applied to the group and compared to postnatal management, in terms of biventricular repair versus single ventricle palliation., Results: Thirty-one fetuses were identified with AS, and eHLHS was identified in 17 at the initial echocardiogram. No fetus with a full eHLHS score (3/3 or 4/4) achieved a biventricular repair. Three fetuses had a favourable threshold score (≥4), one of whom had a successful biventricular outcome. Seven fetuses had an unfavourable threshold score (<4) and underwent a univentricular pathway., Conclusion: The eHLHS score is a reliable predictor for the progression to HLHS at term. The score identifies those who would achieve a biventricular repair postnatally without prenatal intervention. A minority of fetuses with favourable threshold scores may achieve a biventricular repair postnatally without prenatal intervention, but eHLHS and an unfavourable threshold score (<4) predict a single ventricle pathway postnatally., (© 2015 John Wiley & Sons, Ltd.)

Objectives: This study sought to determine the effect of contact force (CF) on atrial lesion size, quality, and transmurality by using a chronic porcine model of radiofrequency ablation., Background: CF is a major determinant of ventricular lesion formation, but uncertainty exists regarding the most appropriate CF parameters to safely achieve permanent, transmural lesions in the atria., Methods: Intercaval linear ablation (30 W, 42°C, 17 ml/min irrigation) was performed in 8 Göttingen minipigs by using a force-sensing catheter with CF >20 g (high force) or <10 g (low force) at alternate ends of the line, separated by an intentional gap. Voltage mapping and cardiovascular magnetic resonance (CMR) imaging were performed pre-ablation, immediately after ablation, and at 2 months' post-procedure. Lesions were sectioned orthogonal to the axis of ablation to assess transmurality., Results: Mean CF was 22.6 ± 11.4 g and 7.8 ± 4.0 g in the high and low CF regions. Acute tissue edema was greater with high CF, both caudally (7.0 mm vs. 4.6 mm; p = 0.016) and cranially (6.9 mm vs. 4.6 mm; p = 0.038). There was no difference in chronic lesion size (voltage mapping) or volume (late gadolinium enhancement CMR) between high and low CF regions. There was no difference in scar density (assessed by low-voltage criteria and late gadolinium enhancement signal intensity) or histological transmurality between high and low CF regions., Conclusions: Although high CF (>20 g) resulted in more acute tissue edema than low CF (<10 g), chronically there was no difference in lesion size, quality, or transmurality. Appropriate CF targets for atrial ablation may be lower than previously thought., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Facial erythema and telangiectasia are commonly associated with the erythematotelangiectatic subtype of rosacea (ETR). It is important for clinicians to recognize that these findings can also be associated with a subtype of photoaging, which we term telangiectatic photoaging (TP)., Objective: To demonstrate that ETR and TP are distinct dermatologic disorders., Design: A case-control observational study comparing clinical, histologic, and gene expression features of 26 participants with ETR, 20 with TP, and 11 age- and sex-matched controls in the Program for Clinical Research in Dermatology at University of Michigan., Main Outcomes and Measures: Findings of clinical history and examination, light and electron microscopy, immunohistochemical analyses, and real-time quantitative reverse-transcriptase polymerase chain reaction gene expression., Results: Transient erythema was greater in the ETR group (38% graded moderate to severe) than in the TP (0%; P < .001) and control groups (0%; P = .002). Nontransient erythema was also greater in the ETR group (50% graded moderate to severe) than in the TP (25%; P = .03) and control groups (0%; P < .001). Participants with ETR tended to have erythema and telangiectasia primarily on the central face (79%), whereas those with TP tended to have more lateral involvement (57%; P < .001). Those with ETR had significantly less clinical evidence of photodamage (0% graded 6-8 on a photonumeric scale) than those with TP (40% graded 6-8; P = .01). Histologically, there was less evidence of photodamage in ETR than in TP, which had wispy collagen and solar elastosis surrounding blood vessels. Immunohistologic analysis demonstrated greater geometric mean immunostained area by mast cell tryptase staining in ETR samples (0.018%) than in TP (0.004%; P = .01) or control samples (0.001%; P < .001) but no increase in mast cell number, indicative of greater mast cell degranulation. Gene expression of matrix metalloproteinase-3 was 4-fold greater in ETR samples than in TP samples (P = .004) and 5-fold higher than in control samples (P = .004). Gene expression of the neuropeptides calcitonin gene-related peptide (CGRP-α) and substance P was significantly increased in ETR compared with TP (9-fold [P < .001] and 5-fold [P = .002], respectively) and control samples (10-fold [P < .001] and 28-fold [P < .001], respectively)., Conclusions and Relevance: Telangiectatic photoaging is characterized by less transient and nontransient erythema, a more lateral distribution of erythema and telangiectasia, less neurogenic mast cell activation, and less MMP-mediated matrix remodeling than ETR. These data demonstrate that TP is a distinct clinical entity from ETR that can be distinguished on the basis of clinical, histologic, and gene expression findings.

Atrial septal defects (ASDs) are among the most common of congenital heart defects and are frequently associated with atrial arrhythmias. Atrial and ventricular geometrical remodelling secondary to the intracardiac shunt promotes evolution of the electrical substrate, predisposing the patient to atrial fibrillation and other arrhythmias. Closure of an ASD reduces the immediate and long-term prevalence of atrial arrhythmias, but the evidence suggests that patients remain at an increased long-term risk in comparison with the normal population. The closure technique itself and its timing impacts future arrhythmia risk profile while subsequent transseptal access following surgical or device closure is complicated. Newer techniques combined with increased experience will help to alleviate some of the difficulties associated with optimal management of arrhythmias in these patients.

Background: Cosmetic laser treatments are frequently performed without anesthesia in the clinic setting and there is a need to better understand the factors that may impact patient pain levels during these procedures. There has been prior research suggesting that there are significant gender-based differences in pain experiences with a variety of interventions., Aims: We sought to examine the influence of gender and specific emotional factors on pain perception during pulsed dye laser treatments., Patients/methods: We conducted a questionnaire-based study of 84 adult patients (42 males and 42 females) who underwent facial pulsed dye laser treatments in our clinic for cosmetic purposes. Questionnaires were completed by each patient after his or her initial laser treatment and patients were queried as to their perceived levels of pain during the procedure. Additional information regarding quality of life measures and patient motivation was also collected., Results: Contrary to prior research suggesting lower pain thresholds for women in other clinical or experimental settings, we found no statistically significant differences in mean pain levels reported between patients of each gender. There was a trend toward females being somewhat more likely than males to see the pain of the treatment as justified for an improvement in appearance., Conclusions: Patient motivation and pain tolerance levels may be similar between genders among patients undergoing non-invasive cosmetic procedures. Clinicians may, therefore, expect patients of either gender to tolerate such treatments equally well.

Advances in surgical technique have had an immense impact on longevity and quality of life in patients with congenital heart disease. However, an inevitable consequence of these surgical successes is the creation of a unique patient population whose anatomy, surgical history and haemodynamics result in the development of a challenging and complex arrhythmia substrate. Furthermore, this patient group remains susceptible to the arrhythmias seen in the general adult population. It is through a thorough appreciation of the cardiac structural defect, the surgical corrective approach, and haemodynamic impact that the most effective arrhythmia care can be delivered. Catheter ablation techniques offer a highly effective management option but require a meticulous attention to the real-time integration of anatomical and electrophysiological information to identify and eliminate the culprit arrhythmia substrate. This review describes the current approach to the interventional management of patients with tachyarrhythmias in the context of congenital heart disease.