Non-invasive three-dimensional electrical activation mapping to predict cardiac resynchronization therapy response: site of latest left ventricular activation relative to pacing site.

AIMS: Pacing remote from the latest electrically activated site (LEAS) in the left ventricle (LV) may diminish response to cardiac resynchronization therapy (CRT). We tested whether proximity of LV pacing site (LVPS) to LEAS, determined by non-invasive three-dimensional electrical activation mapping [electrocardiographic Imaging (ECGI)], increased likelihood of CRT response. METHODS AND RESULTS: Consecutive CRT patients underwent ECGI and chest/heart computed tomography 6-24 months of post-implant. Latest electrically activated site and the distance to LVPS (dp) were assessed. Left ventricular end-systolic volume (LVESV) reduction of ≥15% at clinical follow-up defined response. Logistic regression probabilistically modelled non-response; variables included demographics, heart failure classification, left bundle branch block (LBBB), ischaemic heart disease (IHD), atrial fibrillation, QRS duration, baseline ejection fraction (EF) and LVESV, comorbidities, use of CRT optimization algorithm, angiotensin-converting enzyme inhibitor(ACE)/angiotensin-receptor blocker (ARB), beta-blocker, diuretics, and dp. Of 111 studied patients [64 ± 11 years, EF 28 ± 6%, implant duration 12 ± 5 months (mean ± SD), 98% had LBBB, 38% IHD], 67% responded at 10 ± 3 months post CRT-implant. Latest electrically activated sites were outside the mid-to-basal lateral segments in 35% of the patients. dp was 42 ± 23 mm [31 ± 14 mm for responders vs. 63 ± 24 mm non-responders (P < 0.001)]. Longer dp and the lack of use of CRT optimization algorithm were the only independent predictors of non-response [area under the curve (AUC) 0.906]. dp of 47 mm delineated responders and non-responders (AUC 0.931). CONCLUSION: The distance between LV pacing site and latest electrical activation is a strong independent predictor for CRT response. Non-invasive electrical evaluation to characterize intrinsic activation and guide LV lead deployment may improve CRT efficacy.

Radiomics model-based algorithm for preoperative prediction of pancreatic ductal adenocarcinoma grade.

OBJECTIVE: To develop diagnostic radiomic model-based algorithm for pancreatic ductal adenocarcinoma (PDAC) grade prediction. METHODS: Ninety-one patients with histologically confirmed PDAC and preoperative CT were divided into subgroups based on tumor grade. Two histology-blinded radiologists independently segmented lesions for quantitative texture analysis in all contrast enhancement phases. The ratio of densities of PDAC and unchanged pancreatic tissue, and relative tumor enhancement (RTE) in arterial, portal venous, and delayed phases of the examination were calculated. Principal component analysis was used for multivariate predictor analysis. The selection of predictors in the binary logistic model was carried out in 2 stages: (1) using one-factor logistic models (selection criterion was p < 0.1); (2) using regularization (LASSO regression after standardization of variables). Predictors were included in proportional odds models without interactions. RESULTS: There were significant differences in 4, 16, and 8 texture features out of 62 for the arterial, portal venous, and delayed phases of the study, respectively (p < 0.1). After selection, the final diagnostic model included such radiomics features as DISCRETIZED HU standard, DISCRETIZED HUQ3, GLCM Correlation, GLZLM LZLGE for the portal venous phase of the contrast enhancement, and CONVENTIONAL_HUQ3 for the delayed phase of CT study. On its basis, a diagnostic model was built, showing AUC for grade ≥ 2 of 0.75 and AUC for grade 3 of 0.66. CONCLUSION: Radiomics features vary in PDAC of different grades and increase the accuracy of CT in preoperative diagnosis. We have developed a diagnostic model, including texture features, which can be used to predict the grade of PDAC. KEY POINTS: • A diagnostic algorithm based on CT texture features for preoperative PDAC grade prediction was developed. • The assumption that the scanning protocol can influence the results of texture analysis was confirmed and assessed. • Our results show that tumor differentiation grade can be assessed with sufficient diagnostic accuracy using CT texture analysis presented in this study.

Diagnostic yield and variant reassessment in the genes encoding Nav1.5 channel in Russian patients with Brugada syndrome.

Brugada syndrome (BrS) is an inherited cardiac arrhythmia characterized by ST-elevation, negative T-wave, and a high risk of sudden cardiac death (SCD) due to ventricular tachycardia. It is associated with mutations in over 20 genes but only SCN5A is recommended for routine genetic screening. This study was performed to estimate diagnostic yield and pathogenicity assessment of rare genetic variants in the genes encoding Nav1.5 channel in Russian patients with Brugada syndrome (BrS). Targeted genes panel sequencing of the five genes were screened using IonTorrent PGM with following Sanger confirmation. Detailed clinical evaluation of 75 unrelated BrS probands with a deep phenotyping of SCN5A (+) probands was performed. Twelve rare genetic variants (six missense, six truncating) were initially identified and classified as disease-causing. Reassessment of the clinical significance in the light of the current guidelines revealed: 2 Pathogenic (P) variants; 8 Likely Pathogenic (LP); two missense variants (p.G274S and p. S1778H) were re-classified later as a variant of uncertain significance (VUS). Unique VUS (p.Arg100Ser) was detected in the SCN4B gene. Lone Brugada-pattern was observed in 46% probands; 54% patients had concomitant arrhythmias. PR interval, the only electrocardiography parameter correlating with SCN5A-mutation, was longer (207 ± 24 ms) than normal in SCN5A (+) probands. SCD cases were registered in 31 families. Depression was the only recurring extra-cardiac complaint in SCN5A (+) probands; it was self-reported in five SCN5A (+) probands, and co-segregated with Brugada pattern in 2 families. After variants reassessment, the ratio of SCN5A (+) probands with Brugada syndrome accounts for 13% in Russian cohort.

[What the ablationist should know about pulmonary vein anatomy]. / Was muss der Abladeur zur Anatomie der Pulmonalvenen wissen?

The importance of anatomy in daily clinical practice of the interventional electrophysiologist is crucial, especially for pulmonary vein isolation which is a predominantly anatomy-based approach. Many anatomical and morphological studies focusing on this topic were published in last two decades. In this article we are refreshing the knowledge of anatomy and morphology of the pulmonary veins and present them from a clinical perspective.

Computed tomography-based radiomics approach in pancreatic tumors characterization.

Radiomics (or texture analysis) is a new imaging analysis technique that allows calculating the distribution of texture features of pixel and voxel values depend on the type of ROI (3D or 2D), their relationships in the image. Depending on the software, up to several thousand texture elements can be obtained. Radiomics opens up wide opportunities for differential diagnosis and prognosis of pancreatic neoplasias. The aim of this review was to highlight the main diagnostic advantages of texture analysis in different pancreatic tumors. The review describes the diagnostic performance of radiomics in different pancreatic tumor types, application methods, and problems. Texture analysis in PDAC is able to predict tumor grade and associates with lymphovascular invasion and postoperative margin status. In pancreatic neuroendocrine tumors, texture features strongly correlate with differentiation grade and allows distinguishing it from the intrapancreatic accessory spleen. In pancreatic cystic lesions, radiomics is able to accurately differentiate MCN from SCN and distinguish clinically insignificant lesions from IPMNs with advanced neoplasia. In conclusion, the use of the CT radiomics approach provides a higher diagnostic performance of CT imaging in pancreatic tumors differentiation and prognosis. Future studies should be carried out to improve accuracy and facilitate radiomics workflow in pancreatic imaging.

Immune Status of Pancreatic Cancer Patients Receiving Cryosurgery.

Cryosurgery used on patients with unresectable pancreatic cancer improved their quality of life, but mainly because of the pain relief. In postoperative patients, multifaceted changes in immunity were found, and the state of the immune system prior to surgery often was a decisive factor to indicate whether further disorders in the postoperative period would develop, or by contrast, it would boost its recovery. Some patients receiving cryosurgery showed immune system imbalance and activation, and of antitumor immunity in particular. It has been suggested that the advisability of immunotropic therapy for specific treatment algorithms should be predicted or the therapy should be suspended at some pathologic stage, and this has been immunologically confirmed. Cryosurgery should be considered as a reasonable alternative to the existing types of surgery for pancreatic cancer or as an essential component of multimodal therapy, consisting of topical cryosurgery, chemotherapy, and immunotropic therapy, to boost antitumor immunity and to discontinue cytoreductive therapy due to its toxic effects.

Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial.

Importance: Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective: To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants: The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions: The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures: The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results: Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15]; P = .30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21]; P = .38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93]; P = .001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60]; P < .001). Conclusions and Relevance: Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial. Trial Registration: ClinicalTrials.gov Identifier: NCT00911508.

Overview of the current electrophysiology (EP) state of affairs in Russia.

Russia is the largest country in the world based on the landmass, covering more than one-eighth of the earth's inhabited area. Russia faces challenges in electrophysiology (EP) care including insufficient and uneven financing, complicated system for identifying optimal treatment for individual patients, relative paucity of reasonable educational and certification scope for electrophysiologists, suboptimal national statistical data gathering regarding heart rhythm disorders and EP devices in use, and weak networking of medical information. In comparison with the average level of EP utilization in ESC countries, Russia utilizes around 50% in pacemaker; 10% in ICD; 8% in cardiac resynchronization therapy; 55% in ablations; and 45% in AF ablations. As projected, Russia has the biggest unmet demand in EP procedures, so-called developmental potential in the European region. Nearly 37% of implanted single-chamber and 63% dual-chamber devices are manufactured outside of Russia. The price of the Russian devices is slightly (by 10-20%) lower than the one imported and they are readily provided for patients by the Russian Ministry of Health. Based on the analysis of the data available, we suggest some strategies for the improvement of the EP care in Russia. Solutions include the institution of formal EP education and standardization of it, development of international educational, and scientific collaboration; implementation quality-assessment tools for professional knowledge and skills; wide application of national medical databases and collection of heart rhythm disorders' statistics; growth of financial support of electrophysiology and transparent distribution of financing between state/municipal and private medical centers; enhancement of medical care accessibility countrywide; development of technologies for local EP devices production; and collection of data regarding usage and effectiveness of it.

Noninvasive phase mapping of persistent atrial fibrillation in humans: Comparison with invasive catheter mapping.

BACKGROUND: A novel noninvasive epicardial and endocardial electrophysiology system (NEEES) to identify electrical rotors and focal activity in patients with atrial fibrillation (AF) was recently introduced. Comparison of NEEES data with results from invasive mapping is lacking. METHODS: Six male patients (59 ± 11 years) with persistent AF underwent cardiac mapping with the NEEES, which included the creation of isopotential and phase maps. Then patients underwent catheter mapping using a PentaRay NAV catheter and the CARTO 3 system. Signals acquired by the catheter were analyzed by customized software that applied the same phase mapping algorithm as for the NEEES data. RESULTS: In all patients, noninvasive phase mapping revealed short-lived electrical rotors occurring 1.8 ± 0.3 times per second and demonstrating 1-4 (mean 1.2 ± 0.6) rotation cycles. Most of these rotors (72.7%) aggregated in 2-3 anatomical clusters. In two patients, focal excitation from pulmonary veins was observed. Invasive catheter mapping in the dominant rotor aggregation sites and in the three control sites demonstrated the presence of electrical rotors with properties similar to noninvasively detected rotors. Spearman's correlation coefficient between rotor occurrence rate by noninvasive and invasive mapping was 0.97 (p < .0001). Mean rotors' cycle length at dominant aggregation sites, scores of their full rotations, and the proportion of rotors with clockwise rotation were not significantly different between the mapping modalities. CONCLUSION: In patients with persistent AF, phase processing of unipolar electrograms recorded by catheter mapping could reproduce electrical rotors as characterized by NEEES-based phase mapping.

Unlocking the secrets to regenerating cardiac tissue: an update.

The use of extracellular matrix has evolved into a promising therapeutic approach for the treatment of valve disease and heart failure. Both biomechanical and biochemical signals for tissue remodelling require the presence of the extracellular matrix to recognize the remodelling signals and transfer them to the host stem cells. The extracellular matrix is the key to delivering these signals to the immigrated stem cells, and it also serves as a 'stem cell scaffold' making the possibility of regenerating new cardiac tissue a reality.

Noninvasive epicardial and endocardial mapping of premature ventricular contractions.

AIMS: The aim of the present study was to estimate the accuracy of a novel non-invasive epicardial and endocardial electrophysiology system (NEEES) for mapping ectopic ventricular depolarizations. METHODS AND RESULTS: The study enrolled 20 patients with monomorphic premature ventricular contractions (PVCs) or ventricular tachycardia (VT). All patients underwent pre-procedural computed tomography or magnetic resonance imaging of the heart and torso. Radiographic data were semi-automatically processed by the NEEES to reconstruct a realistic 3D model of the heart and torso. In the electrophysiology laboratory, body-surface electrodes were connected to the NEEES followed by unipolar EKG recordings during episodes of PVC/VT. The body-surface EKG data were processed by the NEEES using its inverse-problem solution software in combination with anatomical data from the heart and torso. The earliest site of activation as denoted on the NEEES 3D heart model was compared with the PVC/VT origin using a 3D electroanatomical mapping system. The site of successful catheter ablation served as final confirmation. A total of 21 PVC/VT morphologies were analysed and ablated. The chamber of interest was correctly diagnosed non-invasively in 20 of 21 (95%) PVC/VT cases. In 18 of the 21 (86%) cases, the correct ventricular segment was diagnosed. Catheter ablation resulted in acute success in 19 of the 20 (95%) patients, whereas 1 patient underwent successful surgical ablation. During 6 months of follow-up, 19 of the 20 (95%) patients were free from recurrence off antiarrhythmic drugs. CONCLUSION: The NEEES accurately identified the site of PVC/VT origin. Knowledge of the potential site of the PVC/VT origin may aid the physician in planning a successful ablation strategy.

Outcomes of Cryoballoon Ablation in High- and Low-Volume Atrial Fibrillation Ablation Centres: A Russian Pilot Survey.

PURPOSE: The results of cryoballoon ablation (CBA) procedure have been mainly derived from studies conducted in experienced atrial fibrillation (AF) ablation centres. Here, we report on CBA efficacy and complications resulting from real practice of this procedure at both high- and low-volume centres. METHODS: Among 62 Russian centres performing AF ablation, 15 (24%) used CBA technology for pulmonary vein isolation. The centres were asked to provide a detailed description of all CBA procedures performed and complications, if encountered. RESULTS: Thirteen sites completed interviews on all CBAs in their centres (>95% of CBAs in Russia). Six sites were high-volume AF ablation (>100 AF cases/year) centres, and 7 were low-volume AF ablation. There was no statistical difference in arrhythmia-free rates between high- and low-volume centres (64.6 versus 60.8% at 6 months). Major complications developed in 1.5% of patients and were equally distributed between high- and low-volume centres. Minor procedure-related events were encountered in 8% of patients and were more prevalent in high-volume centres. Total event and vascular access site event rates were higher in women than in men. CONCLUSIONS: CBA has an acceptable efficacy profile in real practice. In less experienced AF ablation centres, the major complication rate is equal to that in high-volume centres.

Validation of the mapping accuracy of a novel non-invasive epicardial and endocardial electrophysiology system.

AIMS: Use of a non-invasive electrocardiographic mapping system may aid in rapid diagnosis of atrial or ventricular arrhythmias or the detection of ventricular dyssynchrony. The aim of the present study was to validate the mapping accuracy of a novel non-invasive epi- and endocardial electrophysiology system (NEEES). METHODS AND RESULTS: Patients underwent pre-procedural computed tomography or magnetic resonance imaging of the heart and torso. Radiographic data were merged with the data obtained from the NEEES during pacing from implanted pacemaker leads or pacing from endocardial sites using an electroanatomical mapping system (CARTO 3, Biosense Webster). The earliest activation as denoted on the NEEES three-dimensional heart model was compared with the true anatomic location of the tip of the pacemaker lead or the annotated pacing site on the CARTO 3 map. Twenty-nine patients [mean age: 62 ± 11 years, 6/29 (11%) female, 21/29 (72%) with ischaemic cardiomyopathy] were enrolled into the pacemaker verification group. The mean distance from the non-invasively predicted pacing site to the anatomic reference site was 10.8 ± 5.4 mm for the right atrium, 7.7 ± 5.8 mm for the right ventricle, and 7.9 ± 5.7 mm for the left ventricle activated via the coronary sinus lead. Five patients [mean age 65 ± 4 years, 2 (33%) females] underwent CARTO 3 verification study. The mean distance between non-invasively reconstructed pacing site and the reference pacing site was 7.4 ± 2.7 mm for the right atrium, 6.9 ± 2.3 mm for the left atrium, 6.5 ± 2.1 mm for the right ventricle, and 6.4 ± 2.2 for the left ventricle, respectively. CONCLUSION: The novel NEEES was able to correctly identify the site of pacing from various endo- and epicardial sites with high accuracy.

Prospective European survey on atrial fibrillation ablation: clinical characteristics of patients and ablation strategies used in different countries.

BACKGROUND: Atrial fibrillation (AF) ablation is widely adopted. Our aim was to conduct a prospective multicenter survey to verify patients' characteristics, approaches, and technologies adopted across Europe. METHODS AND RESULTS: A total of 35 centers in 12 countries actively participated in the study and 940 patients (median age 60 years) were enrolled. AF was paroxysmal, persistent, and long-lasting persistent in 52.4%, 36%, and 11.6% of patients, respectively; 95.5% of patients were symptomatic and 91.4% were refractory to antiarrhythmic therapy. Redo procedures were performed in 20.9%. Pulmonary vein isolation (PVI) emerged as the cornerstone of ablative therapy and has been performed in 98.7% of procedures, with confirmation of PVI in 92.9% of cases. The ablation of nonparoxysmal AF was not generally limited to isolating the PVs and several adjunctive approaches are adopted, particularly in the case of long-lasting persistent AF. Linear lesions or elimination of complex fractionated atrial electrograms were more frequently added. Circular mapping catheters and imaging techniques were seen to be used in about two-thirds of cases. Radiofrequency energy was delivered through open irrigated catheters in 68% of cases. CONCLUSIONS: European centers are largely following the recommendations of the guidelines and the expert consensus documents for AF ablation. AF ablation is mainly performed in relatively young patients with symptomatic drug refractory AF and no or minimal heart disease. Patients with paroxysmal AF are the most frequently treated with a quite uniform ablative approach across Europe. A less standardized approach was observed in nonparoxysmal AF patients.

Advantages and disadvantages of one-stage and two-stage surgery for arrhythmias and Ebstein's anomaly.

OBJECTIVE: To evaluate efficacy of one-step and two-step surgery approach in patients with arrhythmias combined with Ebstein's anomaly. METHODS: Fifty-three patients with Ebstein's anomaly combined with tachyarrhythmias (58.5% men, 41.5% women, mean age 21.6+/-10.7 years) were operated on. In group A (32 patients), one-step surgical correction (simultaneous intraoperative elimination of arrhythmias and congenital heart defect repair) was performed, whereas in group B (21 patients), two-step surgery was performed with initial elimination of arrhythmogenic substrate by transcatheter radiofrequency ablation (first step) and following surgical repair of congenital heart defect (second step). RESULTS: In group A, total hospital mortality was 3.1% (1 patient) due to initial severe condition of this patient. One-step surgery was effective in 93.5% of cases. Mortality was not observed in group B. Efficacy of transcatheter radiofrequency ablation was 76.2%. CONCLUSIONS: One-stage and two-stage surgery of arrhythmias and Ebstein's anomaly are highly effective. First step of surgery of combined pathology reduces cardiopulmonary bypass time, complications and mortality while performing the second step of congenital heart defect surgery. However, simultaneous approach (one-step surgery) is better in terms of arrhythmia elimination.