Development of Plasmonic Chitosan-Squarate Hydrogels via Bioinspired Nanoparticle Growth.

We report on the bioinspired growth of gold nanoparticles (GNPs) in biocompatible hydrogels to develop plasmonic hybrid materials. The new hydrogel (CS-Sq) is prepared from chitosan and diethylsquarate and is formed via noncovalent interactions rising between the in situ formed ionic squaric acid derivatives and chitosan. Interestingly, when the hydrogel is prepared in the presence of HAuCl4, GNPs with controlled sizes between 15 and 50 nm are obtained, which are homogeneously distributed within the plasmonic hydrogels (GNPs-CS-Sq). We found that the supramolecular nature and the composition of the CS-Sq hydrogels are key for the growth process of GNPs where the squaric derivatives act as reducing agents and the chitosan hydrogel network provides nucleation points and supports the GNPs. Accordingly, the hydrogel acts as a bioinspired reactor and permits to gain certain control on the size of GNPs by adjusting the concentration of chitosan and HAuCl4. Besides the intrinsic and tunable plasmonic properties of the GNPs-CS-Sq hydrogels, it was found that the gels could be useful as heterogeneous catalysts for organic reactions. Furthermore, cell viability studies indicate that the new hydrogels exhibit suitable biocompatibility. Thus, the proposed method for obtaining GNPs-CS-Sq hydrogels has the potential for the development of a wide variety of other hybrid chitosan materials useful for catalysis, biosensing, cell culture, tissue engineering, and drug delivery applications.

Self-assembly of amphiphilic aryl-squaramides in water driven by dipolar π-π interactions.

Squaramides are versatile compounds with a great capacity to interact via non-covalent interactions and therefore of interest for the development of supramolecular systems and functional materials. In the present work, a new series of aryl-squaramide amphiphiles (1-5) were prepared to form supramolecular polymers in water. Interestingly, only compounds 1 and 2 that contain electron-deficient aryl groups are capable of forming hydrogels (∼10-2 M) upon treatment with a base (NaOH or PBS). The aggregation behaviour of 1 and 2 was studied by static light scattering, UV-Vis, 1H NMR, FT-IR, and atomic force microscopy, and it was found that these compounds aggregate forming well-defined 1D nanofibers below the critical gelation concentration (<10-3 M). Moreover, the combination of these experiments with 1D and 2D NMR studies and theoretical calculations revealed that 1 and 2 self-assemble via an unprecedented interaction motif showing dipolar π-π interactions between the squaramide rings and the 4-nitrophenyl or 3,5-bis(trifluoromethyl)phenyl rings of 1 and 2, respectively. Such kinds of assemblies are stabilized by the compensation of the dipole moments of the stacked molecules. This interaction mode contrasts with those typically driving squaramide-based assemblies based on either hydrogen bonds or antiparallel stacking. We believe that this interaction motif is of interest for the design and development of new squaramide nanomaterials with free hydrogen bonding groups, which might be useful in drug delivery applications.

A Remote Nutritional Intervention to Change the Dietary Habits of Patients Undergoing Ablation of Atrial Fibrillation: Randomized Controlled Trial.

BACKGROUND: The Prevention With Mediterranean Diet (PREDIMED) trial supported the effectiveness of a nutritional intervention conducted by a dietitian to prevent cardiovascular disease. However, the effect of a remote intervention to follow the Mediterranean diet has been less explored. OBJECTIVE: This study aims to assess the effectiveness of a remotely provided Mediterranean diet-based nutritional intervention in obtaining favorable dietary changes in the context of a secondary prevention trial of atrial fibrillation (AF). METHODS: The PREvention of recurrent arrhythmias with Mediterranean diet (PREDIMAR) study is a 2-year multicenter, randomized, controlled, single-blinded trial to assess the effect of the Mediterranean diet enriched with extra virgin olive oil (EVOO) on the prevention of atrial tachyarrhythmia recurrence after catheter ablation. Participants in sinus rhythm after ablation were randomly assigned to an intervention group (Mediterranean diet enriched with EVOO) or a control group (usual clinical care). The remote nutritional intervention included phone contacts (1 per 3 months) and web-based interventions with provision of dietary recommendations, and participants had access to a web page, a mobile app, and printed resources. The information is divided into 6 areas: Recommended foods, Menus, News and Online resources, Practical tips, Mediterranean diet classroom, and Your personal experience. At baseline and at 1-year and 2-year follow-up, the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire and a semiquantitative food frequency questionnaire were collected by a dietitian by phone. RESULTS: A total of 720 subjects were randomized (365 to the intervention group, 355 to the control group). Up to September 2020, 560 subjects completed the first year (560/574, retention rate 95.6%) and 304 completed the second year (304/322, retention rate 94.4%) of the intervention. After 24 months of follow-up, increased adherence to the Mediterranean diet was observed in both groups, but the improvement was significantly higher in the intervention group than in the control group (net between-group difference: 1.8 points in the MEDAS questionnaire (95% CI 1.4-2.2; P<.001). Compared with the control group, the Mediterranean diet intervention group showed a significant increase in the consumption of fruits (P<.001), olive oil (P<.001), whole grain cereals (P=.002), pulses (P<.001), nuts (P<.001), white fish (P<.001), fatty fish (P<.001), and white meat (P=.007), and a significant reduction in refined cereals (P<.001), red and processed meat (P<.001), and sweets (P<.001) at 2 years of intervention. In terms of nutrients, the intervention group significantly increased their intake of omega-3 (P<.001) and fiber (P<.001), and they decreased their intake of carbohydrates (P=.02) and saturated fatty acids (P<.001) compared with the control group. CONCLUSIONS: The remote nutritional intervention using a website and phone calls seems to be effective in increasing adherence to the Mediterranean diet pattern among AF patients treated with catheter ablation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03053843; https://www.clinicaltrials.gov/ct2/show/NCT03053843.

A constant postpacing interval in response to overdrive pacing with variable number of beats: An aid in the identification of entrainment for a particular pacing train during macroreentrant atrial tachycardias.

BACKGROUND: When pacing trains with a constant cycle length (CL) but increasing number of beats are introduced during a macroreentrant atrial tachycardia (MAT), the postpacing interval (PPI) is expected to increase if entrainment does not occur but could be stable if entrainment occurs. We tested the ability of PPI analysis to detect entrainment. METHODS: Synchronized pacing trains with increasing number of beats (1-20) were delivered from the coronary sinus (CS) and lateral right atrium (RA) at a CL 20 ms shorter than the MAT CL. Pacing trains were grouped in pairs differing by one-paced beat, and the ∆PPI measured. RESULTS: In an initial prospective cohort of 21 patients (48% had left atrial flutter) the mean ∆PPI was 21.3 ± 5.6 ms for pairs of pacing trains in which neither entrained the MAT and 2.8 ± 1.4 ms for those in which both entrained the MAT (P < .0001). Results were similar for common vs atypical flutter, PPI-TCL ≤30 ms vs PPI-TCL >30 ms, presence vs absence of antiarrhythmic drugs and faster vs slower MAT. When an index pacing train was compared to one with two-paced beats less, a PPI difference of <19 ms identified entrainment with 95% sensitivity and 98% specificity. In a validation cohort of 16 patients, this cut-off value resulted in sensitivity and specificity of 90% and 94%. CONCLUSIONS: A relatively constant ∆PPI in response to overdrive pacing with identical CL but different number of beats allows accurate discrimination between trains that entrained vs those which did not entrain a MAT.

CRITICAL FACTORS AFFECTING THE SELECTIVE TRANSFORMATION OF 5-HYDROXYMETHYLFURFURAL TO 3-HYDROXYMETHYLCYCLOPENTANONE OVER Ni CATALYSTS.

The ring-rearrangement of 5-hydroxymethylfurfural (HMF) to 3-hydroxymethylcyclopentanone (HCPN) was investigated over Ni catalysts supported on different carbon supports and metallic oxides with different structure and acid-base properties. Their catalytic performance was tested in a batch stirred reactor in aqueous solution at 180 oC and 30 bar of H2. Under these conditions, the HMF hydrogenation proceeds through three possible competitive routes: (i) a non-water path leading to the total hydrogenation product, 2,5-di-hydroxymethyl-tetrahydrofuran (DHMTHF), and two parallel acid-catalyzed water-mediated routes responsible for (ii) ring-opening and (iii) ring-rearrangement reaction products. All catalyst systems primarily produced HCPN, but reaction rates and product distribution were influenced by several variables, some of them intensely analyzed in this work. The most proper conditions resulted to be the presence of the medium/strong Lewis's acidity of a Ni/ZrO2 catalyst (initial TOF= 5.99 min-1 and 73 % HCPN selectivity) or the Brønsted acidity originated by an oxidized high surface area graphite, Ni/HSAG-ox (initial TOF= 5.92 min-1 and 87 % HCPN selectivity). However, too high density of acidic sites on the catalyst support (Ni/Al2O3) and sulfur impurities from the HMF feedstock are criticalyl led to catalyst deactivation by coke deposition and Ni poisoning, respectively.

Mediterranean diet and epicardial adipose tissue in patients with atrial fibrillation treated with ablation: a substudy of the 'PREDIMAR' trial.

AIMS: To analyse the relationship between Mediterranean diet (MedDiet) adherence and epicardial adipose tissue (EAT) in patients with atrial fibrillation (AF) and the association between EAT or MedDiet adherence at baseline with AF recurrence after ablation. METHODS AND RESULTS: We included 199 patients from the PREDIMAR trial (PREvención con DIeta Mediterránea de Arritmias Recurrentes), in a single centre in this substudy. All of them had a computed tomography with EAT measurement. Lifestyle and clinical characteristics were obtained at baseline. The traditional MedDiet pattern was defined according to the MedDiet Adherence Screener (MEDAS). Any documented AF > 30 s after ablation was considered a recurrence. Multivariable-adjusted linear and logistic regression models were run to assess the cross-sectional association of MedDiet with EAT, and of EAT with the AF type at baseline. Also, Cox regression models were used to prospectively assess the associations of MedDiet adherence and EAT with AF recurrences after ablation. Median EAT was 135 g (interquartile range: 112-177), and the mean MedDiet score was 7.75 ± 2 points. A higher MEDAS ≥ 7 that was associated with lower odds of an EAT ≥ 135 g [multivariable odds ratio (mOR) = 0.45; 95% CI = 0.22-0.91; P = 0.025] was significantly associated with persistent AF after adjusting for traditional risk factors (mOR: 2.22; 95% CI: 1.03-4.79; P = 0.042). No significant associations were observed between EAT ≥ 135 g and the risk of atrial tachyarrhythmia recurrences after ablation [multivariable-adjusted hazard ratio (mHR) = 1.18; 95% CI: 0.72-1.94; P = 0.512], or between MEDAS ≥ 7 and AF recurrence (mHR = 0.78; 95% CI: 0.47-1.31; P = 0.344). CONCLUSION: In patients with AF, higher adherence to MedDiet is associated with a significantly lower amount of EAT. Epicardial adipose tissue ≥ 135 g was significantly associated with persistent AF.

Mediterranean diet consumption is significantly associated with a lower amount of epicardial adipose tissue in patients with atrial fibrillation treated with ablation. A higher amount of epicardial adipose tissue is significantly associated with a persistent pattern of atrial fibrillation that is well known as a more aggressive and difficult to treat type of atrial fibrillation. The risk of arrhythmic recurrence after ablation tended to be associated with a larger amount of epicardial adipose tissue. Adherence to Mediterranean diet is associated with a non-significantly lower risk of arrhythmic recurrences after ablation.

Acute Right Coronary artery Occlusion During Cooled-Tip Radiofrequency Ablation of the Cavotricuspid Isthmus.

Cooled-tip radiofrequencycatheter ablation of the cavotricuspid isthmus, performed after pulmonary vein isolation, resulted in acute occlusion of the posterolateral branch of the right coronary artery in a 49-year-old male with previously known right coronary artery disease. The occlusion was successfully stented. It is conceivable that previously diseased coronary arteries are more prone to be damaged during ablation.

Bioinspired crowding directs supramolecular polymerisation.

Crowding effects are crucial to maintaining functionality in biological systems, but little is known about their role in analogous artificial counterparts. Within the growing field of supramolecular polymer science, crowding effects have hitherto remained underappreciated. Herein, we show that crowding effects exhibit strong and distinct control over the kinetics, accessible pathways and final outcomes of supramolecular polymerisation processes. In the presence of a pre-formed supramolecular polymer as crowding agent, a model supramolecular polymer dramatically changes its self-assembly behaviour and undergoes a morphological transformation from bundled fibres into flower-like hierarchical assemblies, despite no co-assembly taking place. Notably, this new pathway can only be accessed in crowded environments and when the crowding agent exhibits a one-dimensional morphology. These results allow accessing diverse morphologies and properties in supramolecular polymers and pave the way towards a better understanding of high-precision self-assembly in nature.

The presence of a large patent foramen ovale reduces acute and chronic success in atrial fibrillation ablation.

PURPOSE: In this study, we analyzed PFO implications in atrial fibrillation (AF) ablation. METHODS: Six hundred and twenty-five consecutive patients with AF undergoing PV isolation were included. We considered that a large and/or compliant PFO was present if the catheters advanced gently into the LA without puncturing the septum. Atrial tachyarrhythmias after the 3-month blanking period were classified as a recurrence. RESULTS: Out of the 625 patients included, 36 (5.8%) were found to have PFO. No significant differences were observed in the clinical characteristics of patients with PFO compared with patients without PFO. Nevertheless, patients with PFO had lower acute success in PV isolation compared with patients without PFO (98.2% vs. 88.5%; p = 0.006) even after adjusting for age, sex, type of AF, LA area, cardiomyopathy, time from AF diagnosis to the ablation, and ablation technique (odds ratio: 0.1; 95% confidence interval (CI): 0.02-0.9; p = 0.039). In 546 patients followed more than 6 months, the recurrence rate of any atrial tachyarrhythmia after 18.6 ± 11.9 months was significantly higher in patients with PFO compared with patients without PFO (41.9 vs. 70%; p = 0.012). This difference remained significant after adjusting for age, sex, type of AF, LA area, cardiomyopathy, time from AF diagnosis to the ablation, and ablation technique (hazard ratio: 1.9; 95% CI: 1.1-3.3; p = 0.015). CONCLUSIONS: The presence of a large and/or compliant PFO is an independent factor for PV isolation failure and arrhythmia recurrence rate after the ablation.

Loss of biventricular pacing due to T-wave oversensing.

The benefits obtained with cardiac resynchronization therapy are directly related to the occurrence of continuous biventricular pacing. We report a case of intermittent loss of biventricular pacing due to ventricular oversensing that worsened the functional status of the patient.

Electrogram voltage and pacing threshold before ablation, measured by mini-electrodes, predict parameters indicative of transmural lesions in the human atrium.

PURPOSE: An important attenuation of the atrial signal recorded with mini-electrodes (ME) embedded in an 8-mm tip was associated with a transmural radiofrequency lesion. Our aim was to assess if parameters obtained from ME or conventional bipoles before applications predict successful atrial lesions. METHODS: We prospectively included 33 consecutive patients undergoing cavotricuspid isthmus (CTI) ablation. Electrogram voltages and pacing thresholds were measured with ME and conventional bipoles before and after radiofrequency (RF) applications. The time before the loss of capture during applications was recorded. Lesions were considered successful, in accordance with preclinical data, if ME voltage decreased > 54%. RESULTS: Of 207 applications, 107 could be analyzed. During applications, voltages decreased more in the ME than in the conventional bipoles (66.8 ± 26.1% vs 37.5 ± 42.5%, P = 0.001). Likewise, pacing threshold increased significantly more using the ME (86.3 ± 22.9% ME, 52.6 ± 35.6% conventional, P = 0.001). ME pre-ablation voltages were significantly higher and pacing thresholds significantly lower in successful lesions (voltage 0.88 ± 0.71 vs 0.26 ± 0.18 mV, P = 0.0001; threshold 1.6 ± 1.7 vs 2.8 ± 3.0, P = 0.04). Neither of these parameters with conventional bipoles nor time to loss of capture showed differences. A ME voltage > 0.33 mV and a pacing threshold < 1.5 mA predicted a successful lesion with 0.78 and 0.6 sensitivity and 0.78 and 0.59 specificity. CONCLUSIONS: Certain pre-ablation parameters derived from ME such as electrogram voltage and pacing threshold differ from those obtained by a conventional configuration and can predict a successful atrial lesion.

Epicardial Connections Involving Pulmonary Veins: The Prevalence, Predictors, and Implications for Ablation Outcome.

BACKGROUND: The presence of epicardial connections (ECs) between pulmonary veins (PVs) and other anatomic structures may hinder PV isolation. In this study, we analyzed their prevalence, location, associated factors, and clinical implications. METHODS: Five hundred thirty-four consecutive patients with atrial fibrillation undergoing radiofrequency ablation were included. We considered that an EC was present if: (1) the first pass around the PV antrum did not produce PV isolation and (2) subsequent atrial activation during PV pacing showed that the earliest site was located away from the ablation line and later activation sites were observed near the ablation line. Clinical and electrophysiological variables were collected from all patients. Patients were followed during 12.9±9.4 months, and any documented atrial tachyarrhythmia after the 3-month blanking period was classified as a recurrence. RESULTS: Out of the 534 patients included, 72 (13.5%) were found to have 81 ECs. There was a significant association between the presence of ECs and structural heart disease (15.3% in patients without ECs versus 36.5% in patient with ECs; P<0.001) and patent foramen ovale (4.6% versus 13.5%; P=0.002). The presence of a left common trunk was significantly associated with the absence of ECs (29.6% in patients without ECs versus 16.2% in patients with ECs; P=0.014). Patients with ECs had lower acute success in PV isolation compared with patients without ECs (99.1% versus 86.1%; P<0.001). After adjusting for age, sex, type of atrial fibrillation, left atrium area, hypertension, structural heart disease, presence of left common trunk, patent foramen ovale, and time for atrial fibrillation diagnosis to the ablation, we found a significantly higher risk of atrial tachyarrhythmia recurrences in patients with ECs compared with patients without ECs (hazard ratio, 1.7 [95% CI, 1.1-2.9]; P=0.04). CONCLUSIONS: ECs between PVs and other adjacent structures are frequent in patient with atrial fibrillation (prevalence: 13.5%). Structural heart disease and a patent foramen ovale are strongly associated with the presence of ECs. ECs reduce the acute and chronic success of PV isolation.

Lessons learned in attempting catheter-based interatrial electrical disconnection for nonpharmacologic rate control of atrial fibrillation or flutter.

PURPOSE: Ablation of atrioventricular (AV) conduction and pacemaker implantation is the therapy of last resort for symptomatic atrial tachyarrythmias when rhythm and rate control fail, but is far from ideal. To evaluate whether interatrial electrical disconnection as a result of catheter ablation is feasible and of potential clinical utility as a means of non-pharmacological heart rate control. METHODS: Eleven patients with medically refractory atrial fibrillation or left atrial flutter and symptomatic rapid ventricular response were included. The ablation strategy consisted primarily of right atrial ablation of the interatrial electrical connections, which were located by electroanatomical activation maps performed during coronary sinus stimulation. Successive activation maps were performed as each connection was blocked. If the procedure was considered unsuccessful AV nodal ablation was performed. RESULTS: The coronary sinus ostium was earliest in 10/11 and could be ablated in 5/10 patients. Interatrial conduction block was only achieved in one patient (9.1%). An unexpected AV nodal modulation with an increase in the Wenckebach cycle length (> 50 ms) occurred in 8/11 patients. These patients remained without pacemaker implantation and only 1/8 required AV nodal ablation during the 1-year follow-up. Quality of life questionnaires indicated significant improvement in patients with AV nodal modulation. CONCLUSION: Interatrial electrical disconnection by right atrial catheter ablation is a not feasible with present day technology. The extensive right atrial septal ablation performed resulted in significant AV nodal modulation in most patients, which persisted and resulted in improvement in quality of life.

Twiddling in cardiac resynchronization therapy: 'when length matters'.

We report on a 75-year-old woman who successfully underwent cardiac resynchronization therapy. Two weeks after implantation, right continuous pectoral stimulation appeared. Retraction and dislodgement of the right atrial and right ventricular leads as well as coiling of the three leads around the device generator were observed on chest radiography, but, surprisingly, the left ventricular lead remained unaffected due to its major length to facilitate the manoeuvers of implantation.

Assessment of clockwise cavotricuspid isthmus block based on conduction times during transient entrainment: a prospective study.

BACKGROUND: In typical counterclockwise atrial flutter (AFL), the route of impulse propagation to anteroinferior right atrium (AIRA) during transient entrainment (TE) from the coronary sinus (CS) is expected to be similar to that during pacing from the same CS site during sinus rhythm (SR) when cavotricuspid isthmus (CTI) block has occurred. This could be used to identify CTI block during ablation procedures. METHODS: Thirty-six patients with AFL (cycle length [CL], 240 +/- 25 ms) underwent CTI ablation during AFL. CS pacing was performed at a CL of 20 ms less than AFL CL before ablation (n = 36), and at several CL during SR with conduction through the CTI (n = 21) and after CTI block (n = 36). RESULTS: TE with orthodromic activation of AIRA occurred in all 36 patients. Conduction time from CS to AIRA during TE (T-entr, 199 +/- 29 ms) was significantly longer than during pacing in SR (T-CTI) at the same rate not only with CTI conduction (T-CTI-C, 135 +/- 24 ms, P < 0.001), but also with CTI block (T-CTI-B, 186 +/- 24 ms, P < 0.01). T-entr did not correlate with T-CTI-C, but there was an excellent correlation between T-entr and T-CTI-B (r = 0.874, P < 0.001). A "TE index" that corrected T-CTI for individual T-entr identified CTI block with 97% sensitivity and 91% specificity. T-CTI at low rates differed from T-CTI at high rates but correlated significantly with them. CONCLUSION: Comparison of conduction times during TE from the CS and during pacing from the same site and rate in SR can help to establish whether clockwise CTI block has been achieved in patients with typical AFL.

Atrioventricular nodal tachycardia in a patient with anomalous inferior vena cava with azygos continuation and persistent left superior vena cava.

A 39-year-old female patient was referred for ablation of recurrent episodes of atrioventricular nodal reentrant tachycardia. A combination of an anomalous inferior vena cava with azygos continuation and a persistent left superior vena cava was discovered. A nonfluoroscopic navigation system was very useful for catheter ablation of the tachycardia in this unusual case of anomalous venous system of the heart.

A narrow QRS complex Tachycardia with an apparently concentric retrograde atrial activation sequence.

The retrograde atrial activation sequence constitutes an initial important clue to elucidate the tachycardia mechanism during diagnostic electrophysiological testing in patients with supraventricular tachycardia. However, in some cases its correct analysis is challenging.

Extremely prolonged ventricular asystole.

We are reporting an extremely prolonged sinus arrest documented by Holter monitoring.

Optimization of Lead Placement in the Right Ventricle During Cardiac Resynchronization Therapy. A Simulation Study.

Patients suffering from heart failure and left bundle branch block show electrical ventricular dyssynchrony causing an abnormal blood pumping. Cardiac resynchronization therapy (CRT) is recommended for these patients. Patients with positive therapy response normally present QRS shortening and an increased left ventricle (LV) ejection fraction. However, around one third do not respond favorably. Therefore, optimal location of pacing leads, timing delays between leads and/or choosing related biomarkers is crucial to achieve the best possible degree of ventricular synchrony during CRT application. In this study, computational modeling is used to predict the optimal location and delay of pacing leads to improve CRT response. We use a 3D electrophysiological computational model of the heart and torso to get insight into the changes in the activation patterns obtained when the heart is paced from different regions and for different atrioventricular and interventricular delays. The model represents a heart with left bundle branch block and heart failure, and allows a detailed and accurate analysis of the electrical changes observed simultaneously in the myocardium and in the QRS complex computed in the precordial leads. Computational simulations were performed using a modified version of the O'Hara et al. action potential model, the most recent mathematical model developed for human ventricular electrophysiology. The optimal location for the pacing leads was determined by QRS maximal reduction. Additionally, the influence of Purkinje system on CRT response was assessed and correlation analysis between several parameters of the QRS was made. Simulation results showed that the right ventricle (RV) upper septum near the outflow tract is an alternative location to the RV apical lead. Furthermore, LV endocardial pacing provided better results as compared to epicardial stimulation. Finally, the time to reach the 90% of the QRS area was a good predictor of the instant at which 90% of the ventricular tissue was activated. Thus, the time to reach the 90% of the QRS area is suggested as an additional index to assess CRT effectiveness to improve biventricular synchrony.