Interdependence of photon upconversion performance and antisolvent processing in thin film halide perovskite sensitized triplet triplet annihilators

We prepared triplet triplet annihilation photon upconverters combining thin film methylammonium lead iodide MAPI perovskite with a rubrene annihilator in a bilayer structure. Excitation of the perovskite film leads to delayed, upconverted photoluminescence emitted from the annihilator layer, with triplet excitation of the rubrene being driven by carriers excited in the perovskite layer. To better understand the connections between the semiconductor properties of the perovskite film and the upconversion efficiency, we deliberately varied the perovskite film properties by modifying two spin coating conditions, namely, the choice of antisolvent and the antisolvent dripping time, and then studied the resulting photon upconversion performance with a standard annihilator layer. A stronger upconversion effect was exhibited when the perovskite films displayed brighter and more uniform photoluminescence. Both properties were sensitive to the antisolvent dripping time and were maximized for a dripping time of 20 s measured relative to the end of the spin coating program . Surprisingly, the choice of antisolvent had a significant effect on the upconversion performance, with anisole treated films yielding on average a tenfold increase in upconversion intensity compared to the chlorobenzene treated equivalent. This performance difference was correlated with the carrier lifetime in the perovskite film, which was 52 ns and 306 ns in the brightest chlorobenzene and anisole treated films, respectively. Since the bulk properties of the anisole and chlorobenzene treated films were virtually identical, we concluded that differences in the defect density at the MAPI rubrene interface, linked to the choice of antisolvent, must be responsible for the differing upconversion performanc

Reverse Remodeling of the Atria After Treatment of Chronic Stretch in Humans Implications for the Atrial Fibrillation Substrate

ObjectivesThe aim of this report was to study the effect of chronic stretch reversal on the electrophysiological characteristics of the atria in humans.BackgroundAtrial stretch is an important determinant for atrial fibrillation. Whether relief of stretch reverses the substrate predisposed to atrial fibrillation is unknown.MethodsTwenty-one patients with mitral stenosis undergoing mitral commissurotomy (MC) were studied before and after intervention. Catheters were placed at multiple sites in the right atrium (RA) and sequentially within the left atrium (LA) to determine: effective refractory period (ERP) at 10 sites (600 and 450 ms) and P-wave duration (PWD). Bi-atrial electroanatomic maps determined conduction velocity (CV) and voltage. In 14 patients, RA studies were repeated ≥6 months after MC.ResultsImmediately after MC, there was significant increase in mitral valve area (2.1 ± 0.2 cm2, p < 0.0001) with decrease in LA (23 ± 7 mm Hg to 10 ± 4 mm Hg, p < 0.0001) and pulmonary arterial pressures (38 ± 16 mm Hg to 27 ± 12 mm Hg, p < 0.0001) and LA volume (75 ± 20 ml to 52 ± 18 ml, p < 0.0001). This was associated with reduction in PWD (139 ± 19 ms to 135 ± 20 ms, p = 0.047), increase in CV (LA: 1.3 ± 0.3 mm/ms to 1.7 ± 0.2 mm/ms, p = 0.006; and RA: 1.0 ± 0.1 mm/ms to 1.3 ± 0.3 mm/ms, p = 0.002) and voltage (LA: 1.7 ± 0.6 mV to 2.5 ± 1.0 mV, p = 0.005; and RA: 1.8 ± 0.6 mV to 2.2 ± 0.7 mV, p = 0.09), and no change in ERP. Late after MC, mitral valve area remained at 2.1 ± 0.3 cm2 (p = 0.7) but with further decrease in PWD (113 ± 19 ms, p = 0.04) and RA ERP (at 600 ms, p < 0.0001), with increase in CV (1.0 ± 0.1 mm/ms to 1.3 ± 0.2 mm/ms, p = 0.006) and voltage (1.8 ± 0.7 mV to 2.8 ± 0.6 mV, p = 0.002).ConclusionsThe atrial electrophysiologic and electroanatomic abnormalities that result from chronic stretch due to MS reverses after MC. These observations suggest that the substrate predisposing to atrial arrhythmias might be reversed

Safety of in-hospital insertable cardiac monitor procedures performed outside the traditional settings: results from the Reveal LINQ in-office 2 international study

Duration; Holding area; Insertable cardiac monitorDuració; Sala d'espera; Monitor cardíac inseribleDuración; Sala de espera; Monitor cardíaco insertableBACKGROUND: Historically, the majority of insertable cardiac monitor (ICM) procedures were performed in the cardiac catheterization (cath) lab, electrophysiology (EP) lab, or operating room (OR). The miniaturization of ICMs allows the procedure to be relocated within the hospital without compromising patient safety. We sought to estimate the rate of untoward events associated with procedures performed within the hospital but outside the traditional settings and to characterize resource utilization, procedure time intervals, and physician experience. METHODS: The Reveal LINQ in-Office 2 (RIO 2) International study was a single arm, multicenter, prospective study. Patients indicated for an ICM and willing to undergo device insertion outside the cath/EP lab or OR were eligible and followed for 90 days after insertion. RESULTS: A total of 191 patients (45.5% female aged 63.8 ± 26.9 years) underwent successful Reveal LINQ ICM insertion at 17 centers in Europe, Canada and Australia. The median total visit duration was 106 min (interquartile range [IQR]: 55-61). Patient preparation and patient education accounted for 10 min (IQR: 5-20) and 10 min (IQR: 8-15) of total visit duration, respectively. Preparation and education occurred in the procedure room for 90.6 and 60.2% of patients, respectively. There were no untoward events (0.0, 95% CI: 0.0-2.1%) though four patients presented with procedure-related adverse events that did not require invasive intervention. Physicians rated procedure location as convenient or very convenient. CONCLUSIONS: The Reveal LINQ™ ICM insertion can be safely and efficiently performed in the hospital outside the cath/EP lab or OR. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02412488 ; registered on April 9, 2015.This study was sponsored by Medtronic, Inc

Targeting the Substrate in Ablation of Persistent Atrial Fibrillation: Recent Lessons and Future Directions

While isolation of the pulmonary veins is firmly established as effective treatment for the majority of paroxysmal atrial fibrillation (AF) patients, there is recognition that patients with persistent AF have substrate for perpetuation of arrhythmia existing outside of the pulmonary veins. Various computational approaches have been used to identify targets for effective ablation of persistent AF. This paper aims to discuss the clinical aspects of computational approaches that aim to identify critical sites for treatment. Various analyses of electrogram characteristics have been performed with this aim. Leading techniques for electrogram analysis are Complex Fractionated Atrial Electrograms (CFAE) and Dominant Frequency (DF). These techniques have been the subject of clinical trials of which the results are discussed. Evaluation of the activation patterns of atria in AF has been another avenue of research. Focal Impulse and Rotor Modulation (FIRM) mapping and forms of Body Surface Mapping aim to characterize multiple atrial wavelets, macro-reentry and focal sources which have been proposed as basic mechanisms perpetuating AF. Both invasive and non-invasive activation mapping techniques are reviewed. The presence of atrial fibrosis causes non-uniform anisotropic impulse propagation. Therefore, identification of fibrosis by imaging techniques is an avenue of potential research. The leading contender for imaging-based techniques is Cardiac Magnetic Resonance (CMR). As this technology advances, improvements in resolution and scar identification have positioned CMR as the mode of choice for analysis of atrial structure. AF has been demonstrated to be associated with obesity, inactivity and diseases of modern life. An opportunity exists for detailed computational analysis of the impact of risk factor modification on atrial substrate. This ranges from microstructural investigation through to examination at a population level via registries and public health interventions. Computational analysis of atrial substrate has moved from basic science toward clinical application. Future directions and potential limitations of such analyses are examined in this review

Spatiotemporal characteristics of atrial fibrillation electrograms: a novel marker for arrhythmia stability and termination

Background: Sequentially mapped complex fractionated atrial electrograms (CFAE) and dominant frequency (DF) sites have been targeted during catheter ablation for atrial fibrillation (AF). However, these strategies have yielded variable success and have not been shown to correlate consistently with AF dynamics. Here, we evaluated whether the spatiotemporal stability of CFAE and DF may be a better marker of AF sustenance and termination. Methods: Eighteen sheep with 12 weeks of "one-kidney, one-clip" hypertension underwent open-chest studies. A total of 42 self-terminating (28–100 s) and 6 sustained (>15 min) AF episodes were mapped using a custom epicardial plaque and analyzed in 4-s epochs for CFAE, using the NavX CFE-m algorithm, and DF, using a Fast Fourier Transform. The spatiotemporal stability index (STSI) was calculated using the intraclass correlation coefficient of consecutive AF epochs. Results: A total of 67,733 AF epochs were analyzed. During AF initiation, mean CFE-m and the STSI of CFE-m/DF were similar between sustained and self-terminating episodes, although median DF was higher in sustained AF (p=0.001). During sustained AF, the STSI of CFE-m increased significantly (p=0.02), whereas mean CFE-m (p=0.5), median DF (p=0.07), and the STSI of DF remained unchanged (p=0.5). Prior to AF termination, the STSI of CFE-m was significantly lower (p<0.001), with a physiologically non-significant decrease in median DF (−0.3 Hz, p=0.006) and no significant changes in mean CFE-m (p=0.14) or the STSI of DF (p=0.06). Conclusions: Spatiotemporal stabilization of CFAE favors AF sustenance and its destabilization heralds AF termination. The STSI of CFE-m is more representative of AF dynamics than are the STSI of DF, sequential mean CFE-m, or median DF

Validation of cardiovascular magnetic resonance assessment of pericardial adipose tissue volume

© 2009 Nelson et al; licensee BioMed Central Ltd.Background Pericardial adipose tissue (PAT) has been shown to be an independent predictor of coronary artery disease. To date its assessment has been restricted to the use of surrogate echocardiographic indices such as measurement of epicardial fat thickness over the right ventricular free wall, which have limitations. Cardiovascular magnetic resonance (CMR) offers the potential to non-invasively assess total PAT, however like other imaging modalities, CMR has not yet been validated for this purpose. Thus, we sought to describe a novel technique for assessing total PAT with validation in an ovine model. Methods 11 merino sheep were studied. A standard clinical series of ventricular short axis CMR images (1.5T Siemens Sonata) were obtained during mechanical ventilation breath-holds. Beginning at the mitral annulus, consecutive end-diastolic ventricular images were used to determine the area and volume of epicardial, paracardial and pericardial adipose tissue. In addition adipose thickness was measured at the right ventricular free wall. Following euthanasia, the paracardial adipose tissue was removed from the ventricle and weighed to allow comparison with corresponding CMR measurements. Results There was a strong correlation between CMR-derived paracardial adipose tissue volume and ex vivo paracardial mass (R2 = 0.89, p < 0.001). In contrast, CMR measurements of corresponding RV free wall paracardial adipose thickness did not correlate with ex vivo paracardial mass (R2 = 0.003, p = 0.878). Conclusion In this ovine model, CMR-derived paracardial adipose tissue volume, but not the corresponding and conventional measure of paracardial adipose thickness over the RV free wall, accurately reflected paracardial adipose tissue mass. This study validates for the first time, the use of clinically utilised CMR sequences for the accurate and reproducible assessment of pericardial adiposity. Furthermore this non-invasive modality does not use ionising radiation and therefore is ideally suited for future studies of PAT and its role in cardiovascular risk prediction and disease in clinical practiceAdam J Nelson, Matthew I Worthley, Peter J Psaltis, Angelo Carbone, Benjamin K Dundon, Rae F Duncan, Cynthia Piantadosi, Dennis H Lau, Prashanthan Sanders, Gary A Wittert and Stephen G Worthle

RHYTHM-AF: design of an international registry on cardioversion of atrial fibrillation and characteristics of participating centers

BACKGROUND Atrial fibrillation is a serious public health problem posing a considerable burden to not only patients, but the healthcare environment due to high rates of morbidity, mortality, and medical resource utilization. There are limited data on the variation in treatment practice patterns across different countries, healthcare settings and the associated health outcomes. METHODS/DESIGN RHYTHM-AF was a prospective observational multinational study of management of recent onset atrial fibrillation patients considered for cardioversion designed to collect data on international treatment patterns and short term outcomes related to cardioversion. We present data collected in 10 countries between May 2010 and June 2011. Enrollment was ongoing in Italy and Brazil at the time of data analysis. Data were collected at the time of atrial fibrillation episode in all countries (Australia, Brazil, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom), and cumulative follow-up data were collected at day 60 (±10) in all but Spain. Information on center characteristics, enrollment data, patient demographics, detail of atrial fibrillation episode, medical history, diagnostic procedures, acute treatment of atrial fibrillation, discharge information and the follow-up data on major events and rehospitalizations up to day 60 were collected. DISCUSSIN A total of 3940 patients were enrolled from 175 acute care centers. 70.5% of the centers were either academic (44%) or teaching (26%) hospitals with an overall median capacity of 510 beds. The sites were mostly specialized with anticoagulation clinics (65.9%), heart failure (75.1%) and hypertension clinics (60.1%) available. The RHYTHM-AF registry will provide insight into regional variability of antiarrhythmic and antithrombotic treatment of atrial fibrillation, the appropriateness of such treatments with respect to outcomes, and their cost-efficacy. Observations will help inform strategies to improve cardiovascular outcomes in patients with atrial fibrillation. TRIAL REGISTRATION Clinical trials NCT01119716Harry JGM Crijns, Lori D Bash, François Chazelle, Jean-Yves Le Heuzey, Thorsten Lewalter, Gregory YH Lip, Aldo P Maggioni, Alfonso Martín, Piotr Ponikowski, Mårten Rosenqvist, Prashanthan Sanders, Mauricio Scanavacca, Alexandra A Bernhardt, Sreevalsa Unniachan, Hemant M Phatak and Anselm K Git

Characteristics of the phenotype of mixed cardiomyopathy in patients with implantable cardioverter-defibrillators

OnlinePublBackground or Purpose The prognosis of mixed cardiomyopathy (CMP) in patients with implanted cardioverter-defbrillators (ICDs) has not been investigated. We aim to study the demographic, clinical, device therapies and survival characteristics of mixed CMP in a cohort of patients implanted with a defbrillator. Methods The term mixed CMP was used to categorise patients with impaired left ventricular ejection fraction attributed to documented non-ischemic triggers with concomitant moderate coronary artery disease. This is a single center observational cohort of 526 patients with a mean follow-up of 8.7±3.5 years. Results There were 42.5% patients with ischemic cardiomyopathy (ICM), 26.9% with non-ischemic cardiomyopathy (NICM) and 30.6% with mixed CMP. Mixed CMP, compared to NICM, was associated with higher mean age (69.1 ± 9.6 years), atrial fibrillation (55.3%) and greater incidence of comorbidities. The proportion of patients with mixed CMP receiving device shocks was 23.6%, compared to 18.4% in NICM and 27% in ICM. The VT cycle length recorded in mixed CMP (281.6 ± 43.1 ms) was comparable with ICM (282.5 ± 44 ms; p = 0.9) and lesser than NICM (297.7±48.7 ms; p=0.1). All-cause mortality in mixed CMP (21.1%) was similar to ICM (20.1%; p=0.8) and higher than NICM (15.6%; p = 0.2). The Kaplan–Meier curves revealed hazards of 1.57 (95% CI: 0.91, 2.68) for mixed CMP compared to NICM. Conclusion In a cohort of patients with ICD, the group with mixed CMP represents a phenotype predominantly comprised of the elderly with a higher incidence of comorbidities. Mixed CMP resembles ICM in terms of number of device shocks and VT cycle length. Trends of long-term prognosis of patients with mixed CMP are worse than NICM and similar to ICM.Deep Chandh Raja, Indira Samarawickrema, Sarat Krishna Menon, Rikvin Singh, Abhinav Mehta, Lukah Q. Tuan, Ulhas Pandurangi, Sanjiv Jain, David J. Callans, Francis E. Marchlinski, Walter P. Abhayaratna, Prashanthan Sanders, Rajeev K. Patha

Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in Obese Individuals With Atrial Fibrillation The CARDIO-FIT Study

AbstractBackgroundObesity begets atrial fibrillation (AF). Although cardiorespiratory fitness is protective against incident AF in obese individuals, its effect on AF recurrence or the benefit of cardiorespiratory fitness gain is unknown.ObjectivesThis study sought to evaluate the role of cardiorespiratory fitness and the incremental benefit of cardiorespiratory fitness improvement on rhythm control in obese individuals with AF.MethodsOf 1,415 consecutive patients with AF, 825 had a body mass index ≥27 kg/m2 and were offered risk factor management and participation in a tailored exercise program. After exclusions, 308 patients were included in the analysis. Patients underwent exercise stress testing to determine peak metabolic equivalents (METs). To determine a dose response, cardiorespiratory fitness was categorized as: low (<85%), adequate (86% to 100%), and high (>100%). Impact of cardiorespiratory fitness gain was ascertained by the objective gain in fitness at final follow-up (≥2 METs vs. <2 METs). AF rhythm control was determined using 7-day Holter monitoring and AF severity scale questionnaire.ResultsThere were no differences in baseline characteristics or follow-up duration between the groups defined by cardiorespiratory fitness. Arrhythmia-free survival with and without rhythm control strategies was greatest in patients with high cardiorespiratory fitness compared to adequate or low cardiorespiratory fitness (p < 0.001 for both). AF burden and symptom severity decreased significantly in the group with cardiorespiratory fitness gain ≥2 METs as compared to <2 METs group (p < 0.001 for all). Arrhythmia-free survival with and without rhythm control strategies was greatest in those with METs gain ≥2 compared to those with METs gain <2 in cardiorespiratory fitness (p < 0.001 for both).ConclusionsCardiorespiratory fitness predicts arrhythmia recurrence in obese individuals with symptomatic AF. Improvement in cardiorespiratory fitness augments the beneficial effects of weight loss. (Evaluating the Impact of a Weight Loss on the Burden of Atrial Fibrillation [AF] in Obese Patients; ACTRN12614001123639