Anatomical targets and expected outcomes of catheter-based ablation of atrial fibrillation in 2020.

Anatomical-based approaches, targeting either pulmonary vein isolation (PVI) or additional extra PV regions, represent the most commonly used ablation treatments in symptomatic patients with atrial fibrillation (AF) recurrences despite antiarrhythmic drug therapy. PVI remains the main anatomical target during catheter-based AF ablation, with the aid of new technological advances as contact force monitoring to increase safety and effective radiofrequency (RF) lesions. Nowadays, cryoballoon ablation has also achieved the same level of scientific evidence in patients with paroxysmal AF undergoing PVI. In parallel, electrical isolation of extra PV targets has progressively increased, which is associated with a steady increase in complex cases undergoing ablation. Several atrial regions as the left atrial posterior wall, the vein of Marshall, the left atrial appendage, or the coronary sinus have been described in different series as locations potentially involved in AF initiation and maintenance. Targeting these regions may be challenging using conventional point-by-point RF delivery, which has opened new opportunities for coadjuvant alternatives as balloon ablation or selective ethanol injection. Although more extensive ablation may increase intraprocedural AF termination and freedom from arrhythmias during the follow-up, some of the targets to achieve such outcomes are not exempt of potential severe complications. Here, we review and discuss current anatomical approaches and the main ablation technologies to target atrial regions associated with AF initiation and maintenance.This work was supported by the European Regional Development Fund, the Spanish Ministry of Science and Innovation (SAF2016- 80324-R), and the Fundación Interhospitalaria para la Investigación Cardiovascular (FIC). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Science and Innovation and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Giulio La Rosa has received a fellowship grant from the joint program between the Heart Rhythm Association of the Spanish Society of Cardiology (ARC) and CNIC.S

Mapping Technologies for Catheter Ablation of Atrial Fibrillation Beyond Pulmonary Vein Isolation

Catheter ablation remains the most effective and relatively minimally invasive therapy for rhythm control in patients with AF. Ablation has consistently shown a reduction of arrhythmia-related symptoms and significant improvement in patients’ quality of life compared with medical treatment. The ablation strategy relies on a well-established anatomical approach of effective pulmonary vein isolation. Additional anatomical targets have been reported with the aim of increasing procedure success in complex substrates. However, larger ablated areas with uncertainty of targeting relevant regions for AF initiation or maintenance are not exempt from the potential risk of complications and pro-arrhythmia. Recent developments in mapping tools and computational methods for advanced signal processing during AF have reported novel strategies to identify atrial regions associated with AF maintenance. These novel tools – although mainly limited to research series – represent a significant step forward towards the understanding of complex patterns of propagation during AF and the potential achievement of patient-tailored AF ablation strategies for the near future

Lesion Index Titration Using Contact-Force Technology Enables Safe and Effective Radiofrequency Lesion Creation at the Root of the Aorta and Pulmonary Artery

BACKGROUND: Ablation of some myocardial substrates requires catheter-based radiofrequency delivery at the root of a great artery. We studied the safety and efficacy parameters associated with catheter-based radiofrequency delivery at the root of the aorta and pulmonary artery. METHODS: Thirty-six pigs underwent in-vivo catheter-based ablation under continuous contact-force and lesion index (power, contact-force, and time) monitoring during 60-s radiofrequency delivery with an open-irrigated tip catheter. Twenty-eight animals were allocated to groups receiving 40 W (n=9), 50 W (n=10), or 60 W (n=9) radiofrequency energy, and acute (n=22) and chronic (n=6) arterial wall damage was quantified by multiphoton microscopy in ex vivo samples. Adjacent myocardial lesions were quantified in parallel samples. The remaining 8 pigs were used to validate safety and efficacy parameters. RESULTS: Acute collagen and elastin alterations were significantly associated with radiofrequency power, although chronic assessment revealed vascular wall recovery in lesions without steam pop. The main parameters associated with steam pops were median peak temperature >42°C and impedance falls >23 ohms. Unlike other parameters, lesion index values of 9.1 units (interquartile range, 8.7-9.8) were associated with the presence of adjacent myocardial lesions in both univariate ( P=0.03) and multivariate analyses ( P=0.049; odds ratio, 1.99; 95% CI, 1.02-3.98). In the validation group, lesion index values using 40 W over a range of contact-forces correlated with the size of radiofrequency lesions (R2=0.57; P=0.03), with no angiographic or histopathologic signs of coronary artery damage. CONCLUSIONS: Lesion index values obtained during 40 W radiofrequency applications reliably monitor safe and effective lesion creation at the root of the great arteries.This study was supported by the Fundación Interhospitalaria para la Investigación Cardiovascular (FIC) and the Heart Rhythm Section of the Spanish Society of Cardiology. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation. The CNIC is a Severo Ochoa Center of Excellence (SEV-2015- 0505). This study was supported by grants from Fondo Europeo de Desarrollo Regional (CB16/11/00458) and the Spanish Ministry of Science, Innovation and Universities (SAF2016-80324-R).S

Aneurismas de aorta ascendente y válvula aórtica: comparación de la histología de la aorta descendente en pacientes con válvula aórtica bicúspide y pacientes con válvula aórtica tricúspide

"INTRODUCCIÓN": La válvula aórtica bicúspide (VAB) es la cardiopatía congénita más frecuente y afecta al 0,5-2 por ciento de la población. Los pacientes con VAB tienen mayor predisposición al desarrollo de dilatación aórtica, conocido factor de riesgo para el desarrollo de disección y-o rotura aórtica. Los mecanismos que conducen a la dilatación aórtica en estos pacientes no son bien conocidos, pero podrían relacionarse con una debilidad estructural congénita en la pared aórtica (aortopatía bicúspide). La hipótesis de este trabajo es que los aneurismas que se desarrollan en el seno de una VAB deberían presentar características histológicas distintivas respecto a los que aparecen en los pacientes con válvula aórtica tricúspide (VAT). "MÉTODOS": Se incluyeron de forma prospectiva 134 pacientes (75 por ciento varones, edad media 63 años) sometidos a cirugía electiva sobre la aorta ascendente y se clasificaron en dos grupos en función de la morfología valvular. Se obtuvieron muestras de aorta ascendente durante la intervención y se estudiaron los siguientes aspectos histológicos: grosor total de la capa media, patrón de vascularización de la capa media y los cambios degenerativos (fibrosis, fragmentación de las fibras elásticas, necrosis quística de la media y calcificación). Se construyeron además modelos de regresión para estudiar el impacto de otras variables clínicas en los hallazgos histológicos. "RESULTADOS": No se encontraron diferencias en cuanto al grosor de la capa media entre los dos grupos de pacientes. Los pacientes con VAT mostraron una vascularización más rica de la capa media, caracterizada por una mayor profundidad de penetración de los vasa vasorum. Además presentaron mayor grado de fibrosis y de fragmentación de las fibras elásticas, pero no se encontraron diferencias entre los dos grupos en cuanto a la necrosis quística de la media o la presencia de calcificación en la capa media. En el análisis multivariado la morfología valvular fue predictor independiente de la penetración de los vasa vasorum, pero no de los cambios degenerativos analizados

Safety threshold of R-wave amplitudes in patients with implantable cardioverter defibrillator

Objective: A safety threshold for baseline rhythm R-wave amplitudes during follow-up of implantable cardioverter defibrillators (ICD) has not been established. We aimed to analyse the amplitude distribution and undersensing rate during spontaneous episodes of ventricular fibrillation (VF), and define a safety amplitude threshold for baseline R-waves. Methods: Data were obtained from an observational multicentre registry conducted at 48 centres in Spain. Baseline R-wave amplitudes and VF events were prospectively registered by remote monitoring. Signal processing algorithms were used to compare amplitudes of baseline R-waves with VF R-waves. All undersensed R-waves after the blanking period (120 ms) were manually marked. Results: We studied 2507 patients from August 2011 to September 2014, which yielded 229 VF episodes (cycle length 189.6±29.1 ms) from 83 patients that were suitable for R-wave comparisons (follow-up 2.7±2.6 years). The majority (77.6%) of VF R-waves (n=13953) showed lower amplitudes than the reference baseline R-wave. The decrease in VF amplitude was progressively attenuated among subgroups of baseline R-wave amplitude (≥17; ≥12 to <17; ≥7 to <12; ≥2.2 to <7 mV) from the highest to the lowest: median deviations -51.2% to +22.4%, respectively (p=0.027). There were no significant differences in undersensing rates of VF R-waves among subgroups. Both the normalised histogram distribution and the undersensing risk function obtained from the ≥2.2 to <7 mV subgroup enabled the prediction that baseline R-wave amplitudes ≤2.5 mV (interquartile range: 2.3-2.8 mV) may lead to ≥25% of undersensed VF R-waves. Conclusions: Baseline R-wave amplitudes ≤2.5 mV during follow-up of patients with ICDs may lead to high risk of delayed detection of VF. Trial registration number: NCT01561144; results.Depto. de MedicinaFac. de MedicinaTRUEpu

QRS duration reflects underlying changes in conduction velocity during increased intraventricular pressure and heart failure

Pressure overload and heart failure electrophysiological remodeling (HF-ER) in pigs are associated with decreased conduction velocity (CV) and dispersion of repolarization, which lead to higher risk of ventricular arrhythmia. This work aimed to establish the correlation between QRS complex duration and underlying changes in CV during increased intraventricular pressure (IVP) and/or HF-ER ex-vivo, and to determine whether QRS duration could be sensitive to an acute increase in left ventricular (LV) afterload in-vivo. HF-ER was induced in 7 pigs by high-rate ventricular pacing. Seven weight-matched animals were used as controls. Isolated Langendorff-perfused hearts underwent programmed ventricular stimulation to study QRS complex duration and CV under low/high IVP, using volume-conducted ECG and epicardial optical mapping, respectively. Four additional pigs underwent open-chest surgery to increase LV afterload by partially clamping the ascending aorta, while measuring QRS complex duration during sinus rhythm (SR). In 13 hearts included for analysis, both HF-ER and increased IVP showed significantly slower epicardial CV (-40% and -15%, p < 0.001 and p = 0.004, respectively), which correlated with similar widening of the QRS complex (+41% and +17%, p = 0.005 and p < 0.001, respectively). HF-ER hearts shower larger prolongation of the QRS complex than controls upon increasing the IVP (+21% vs. +12%, respectively. HF-ER*IVP interaction: p = 0.004). QRS complex widened after increasing LV afterload in-vivo (n=3), with correlation between QRS duration and aortic diastolic pressures (R = 0.58, p < 0.001). In conclusion, high IVP and/or HF-ER significantly decrease CV, which correlates with QRS widening on the ECG during ventricular pacing. Increased myocardial wall stress also widens the QRS complex during SR in-vivo.The CNIC is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This study was supported by grants from Fondo Europeo de Desarrollo Regional (CB16/11/00458), Instituto de Salud Carlos III [RD06/0003/0009 (REDINSCOR), RD12/0042/0036 (RIC)], and Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2016-80324-R). The study was also partially supported by the Fundacion Interhospitalaria para la Investigacion Cardiovascular (FIC).S

Implications of bipolar voltage mapping and magnetic resonance imaging resolution in biventricular scar characterization after myocardial infarction

Aims: We aimed to study the differences in biventricular scar characterization using bipolar voltage mapping compared with state-of-the-art in vivo delayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging and ex vivo T1 mapping. Methods and results: Ten pigs with established myocardial infarction (MI) underwent in vivo scar characterization using LGE-CMR imaging and high-density voltage mapping of both ventricles using a 3.5-mm tip catheter. Ex vivo post-contrast T1 mapping provided a high-resolution reference. Voltage maps were registered onto the left and right ventricular (LV and RV) endocardium, and epicardium of CMR-based geometries to compare voltage-derived scars with surface-projected 3D scars. Voltage-derived scar tissue of the LV endocardium and the epicardium resembled surface projections of 3D in vivo and ex vivo CMR-derived scars using 1-mm of surface projection distance. The thinner wall of the RV was especially sensitive to lower resolution in vivo LGE-CMR images, in which differences between normalized low bipolar voltage areas and CMR-derived scar areas did not decrease below a median of 8.84% [interquartile range (IQR) (3.58, 12.70%)]. Overall, voltage-derived scars and surface scar projections from in vivo LGE-CMR sequences showed larger normalized scar areas than high-resolution ex vivo images [12.87% (4.59, 27.15%), 18.51% (11.25, 24.61%), and 9.30% (3.84, 19.59%), respectively], despite having used optimized surface projection distances. Importantly, 43.02% (36.54, 48.72%) of voltage-derived scar areas from the LV endocardium were classified as non-enhanced healthy myocardium using ex vivo CMR imaging. Conclusion: In vivo LGE-CMR sequences and high-density voltage mapping using a conventional linear catheter fail to provide accurate characterization of post-MI scar, limiting the specificity of voltage-based strategies and imaging-guided procedures.The CNIC (Madrid, Spain) is supported by the Ministry of Economy, Industry and Competitiveness (MEIC) and the Pro CNIC Foundation; The CNIC and the BSC (Barcelona, Spain) are Severo Ochoa Centers of Excellence (SEV-2015-0505 and SEV-2011-0067, respectively); Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (RD12/0042/0036, CB16/11/00458), Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2016-80324-R, PI16/02110, and DTS17/00136), and by the European Commission [ERA-CVD Joint Call (JTC2016/APCIN-ISCIII-2016), Grant no. AC16/00021]; Fundacion Interhospitalaria para la Investigacion Cardiovascular (FIC, Madrid, Spain) and the heart rhyhtm section of the Spanish Society of Cardiology (DFR), in part; R01 Grant HL122352 from the National Heart Lung and Blood Institute, USA, National Institutes of Health to J.J.; CompBioMed project, H2020-EU.1.4.1.3 European Union's Horizon 2020 research and innovation program, (Grant no. 675451 to J.A.-S.); D.G.L. has received financial support through the 'la Caixa' Fellowship Grant for Doctoral Studies, 'la Caixa' Banking Foundation, Barcelona, Spain.S