Modificaciones farmacológicas de las propiedades electrofisiológicas cardíacas. Estudio experimental y simulación con modelos matemáticos.

RESUMEN INTRODUCCIÓN: Se ha estudiado en un modelo experimental y mediante simulación con modelos matemáticos, el efecto de tres fármacos (flecainida, dofetilide y pinacidil) sobre las propiedades electrofisiológicas ventriculares en condiciones basales y en circunstancias tales como la fibrilación ventricular (FV) y la isquemia aguda regional (IAR). MATERIAL Y MÉTODOS: se han utilizado 56 preparaciones de corazón aislado y perfundido de conejo según la técnica de Langendorff. El sistema de registro ha sido mediante placas electrodo situadas en la superficie epicárdica, compuestas bien por 121, 114 o 235 electrodos unipolares según el protocolo experimental. La estimulación se ha realizado mediante un electrodo bipolar de acero inoxidable. Se han realizado tres grupos experimentales para el estudio de cada fármaco. En 11 experimentos se ha estudiado el efecto de 1 μmolar de flecainida sobre las velocidades de conducción ventricular longitudinal (VL) y transversal (VT) con tres intervalos de acoplamiento decrecientes, así como la influencia del intervalo de acoplamiento (IA) en el mismo y el predominio de los efectos del fármaco sobre la VL versus VT. En 17 experimentos se ha estudiado el efecto de 0.5 μmolar de dofetilide sobre los periodos refractarios ventriculares (PR) y sobre la velocidad de conducción ventricular (VC) con cuatro ciclos base diferentes, así como el efecto de concentraciones crecientes de fármaco (1-5-10 μmolar) sobre el patrón fibrilatorio. El patrón fibrilatorio se ha estudiado mediante análisis espectral según la técnica de Welch, mediante análisis en el dominio del tiempo y mediante el estudio de los mapas de activación epicárdicos. En 28 preparaciones se ha estudiado el efecto de 10 μmolar de pinacidil sobre los PR y la inducibilidad de FV en condiciones basales y de isquemia aguda, así como los patrones de activación ventricular de la arritmia en su inicio. El estudio del pinacidil se ha completado con simulación de tejidos unidimensionales y bidimensionales mediante modelos matemáticos modernos basados en las características del potencial de acción y de las corrientes iónicas transmembrana. RESULTADOS Y CONCLUSIONES: la flecainida acortó significativamente la VL y VT para cada intervalo de acoplamiento estudiado, mostrando mayor efecto conforme se acortó el IA sólo en el caso de la VL. Para IA largos la flecainida afectó más a la VT, efecto que se igualó entre ambas VC para IA cortos. El dofetilide alargó los PR de forma significativa con un efecto inverso dependiente de la frecuencia, sin afectar a la VC. Este efecto se tradujo en una reducción en la complejidad del patrón fibrilatorio en ambos ventrículos, pero de forma mas acusada en el ventrículo derecho. Se produjo el cese de la arritmia únicamente en tres casos. El pinacidil acortó los PR, efecto que quedó encubierto, según los resultados con modelos matemáticos, por un aumento de la refractariedad postrepolarización en condiciones de IAR. El fármaco mostró un efecto protector contra la FV en el minuto 5 de isquemia, efecto que se perdió al analizar el fenómeno globalmente a los 30 minutos de isquemia, donde el pinacidil no mostró efecto protector aunque tampoco aumentó la incidencia de FV con respecto al grupo control. El efecto protector del pinacidil en el minuto 5 de isquemia se relacionó, según los resultados con modelos matemáticos, con la concentración del fármaco utilizada. Los resultados con modelos sugirieron como mecanismo protector del pinacidil, la tendencia del fármaco a producir bloqueos bidireccionales y no unidireccionales, como consecuencia de la reducción de la excitabilidad celular derivada de la fuerte activación de la corriente IKATP en presencia de corrientes de sodio deprimidas por la isquemia. __________________________________________________________________________________________________INTRODUCTION: The effects of three drugs (flecainide, dofetilide and pinacidil) on ventricular electrophysiological properties were studied in both an experimental model of rabbit heart (perfused Langendorff preparation) and with mathematical simulation models (only for pinacidil). METHODS: in 11 experimental preparations, the effect of flecainide 1 μmol/L on longitudinal and transversal conduction velocity was tested using three different coupling intervals. In 17 preparations, the effect of 0.5 μmol/L dofetilide on conduction velocity and refractoriness was studied using four different cycle lengths, as well as the effects of dofetilide (1, 5 and 10 µmol/L) on ventricular fibrillatory patterns. The effects of 10 µmol/L pinacidil on ventricular refractoriness and on ventricular fibrillation induction in basal conditions and in acute myocardial ischemia were studied using 28 experimental preparations and mathematical models. RESULTS: flecainida decreased both longitudinal and transversal conduction velocity, showing a use-dependent effect only in the case of longitudinal conduction velocity. With short coupling intervals, the effect of flecainida was greater for transversal than for longitudinal conduction velocity. Dofetilide (0.5 µmol/L) caused an increase in ventricular refractoriness in a reverse-use-dependent manner, without affecting ventricular conduction times. Increasing drug concentration from 1 to 10 µmol/L caused a reduction on the complexity of ventricular fibrillation patterns specially on the right ventricle, suppressing the arrhythmia only in three cases. Pinacidil (10 μmol/L) caused a decrease in ventricular refractoriness in basal conditions but not in ischemic conditions, due to an increase of post-repolarization refractoriness in the latter, as suggested by simulation results. Pinacidil showed protection action against ventricular fibrillation in the fifth minute of acute regional ischemia in a concentration dependent manner, due (as suggested by simulation results) to the induction of bidirectional (and not unidirectional) conduction block as a consequence of a reduction in cellular excitability caused by the strong activation of the IK(ATP) current in the presence of an ischemic-depressed sodium current

Rethinking Rural Development

La persistencia de la pobreza en las áreas rurales y la creciente desigualdad en la distribución de los ingresos rurales continúan siendo hoy en día aspectos no resueltos en la lucha para combatir la pobreza y la desigualdad en la mayoría de los países del mundo; tres cuartas partes de las 1.200 millones de personas que sobreviven con menos de 1 dólar diario habitan y trabajan en las zonas rurales. Lo cual resulta contradictorio con el hecho de que los fondos destinados al sector agrícola y rural han decrecido más que en otros sectores en los últimos años. Tomando este punto de partida, el prestigioso centro de pensamiento sobre desarrollo británico Overseas Development Institute (ODI) dedicó, en diciembre de 2001, un monográfico de su revista Development Policy Review (Vol. 19-4: pp. 395-573) a la reflexión sobre el concepto y prácticas del desarrollo rural. Editado por Caroline Ashley y Simon Maxwell, recoge trece aportaciones de diversos autores, estructurados en tres ejes, con el objetivo de contribuir a un necesario replanteamiento del desarrollo rural.La persistència de la pobresa a les àrees rurals i la creixent desigualtat en la distribució dels ingressos rurals continuen sent avui en dia aspectes no resolts en la lluita per a combatre la pobresa i la desigualtat a la majoria dels països del món; tres quartes parts dels 1.200 milions de persones que sobreviuen amb menys d'1 dòlar diari habiten i treballen a les zones rurals. La qual cosa resulta contradictòria amb el fet que els fons destinats al sector agrícola i rural han decrescut més que en altres sectors en els últims anys. Prenent aquest punt de partida, el prestigiós centre de pensament sobre desenvolupament britànic Overseas Development Institute (ODI) va dedicar, el desembre del 2001, un monogràfic de la seva revista Development Policy Review (Vol. 19-4: Pp. 395-573) a la reflexió sobre el concepte i pràctiques del desenvolupament rural. Editat per Caroline Ashley i Simon Maxwell, recull tretze aportacions de diversos autors, estructurats en tres eixos, amb l'objectiu de contribuir a un necessari replantejament del desenvolupament rural.Peer Reviewe

Definir el desarrollo rural desde nuevos parámetros

La persistencia de la pobreza en las áreas rurales y la creciente desigualdad en la distribución de los ingresos rurales continúan siendo hoy en día aspectos no resueltos en la lucha para combatir la pobreza y la desigualdad en la mayoría de los países del mundo; tres cuartas partes de las 1.200 millones de personas que sobreviven con menos de 1 dólar diario habitan y trabajan en las zonas rurales. Lo cual resulta contradictorio con el hecho de que los fondos destinados al sector agrícola y rural han decrecido más que en otros sectores en los últimos años.Peer Reviewe

Three-dimensional cardiac computational modelling: methods, features and applications

[EN] The combination of computational models and biophysical simulations can help to interpret an array of experimental data and contribute to the understanding, diagnosis and treatment of complex diseases such as cardiac arrhythmias. For this reason, three-dimensional (3D) cardiac computational modelling is currently a rising field of research. The advance of medical imaging technology over the last decades has allowed the evolution from generic to patient-specific 3D cardiac models that faithfully represent the anatomy and different cardiac features of a given alive subject. Here we analyse sixty representative 3D cardiac computational models developed and published during the last fifty years, describing their information sources, features, development methods and online availability. This paper also reviews the necessary components to build a 3D computational model of the heart aimed at biophysical simulation, paying especial attention to cardiac electrophysiology (EP), and the existing approaches to incorporate those components. We assess the challenges associated to the different steps of the building process, from the processing of raw clinical or biological data to the final application, including image segmentation, inclusion of substructures and meshing among others. We briefly outline the personalisation approaches that are currently available in 3D cardiac computational modelling. Finally, we present examples of several specific applications, mainly related to cardiac EP simulation and model-based image analysis, showing the potential usefulness of 3D cardiac computational modelling into clinical environments as a tool to aid in the prevention, diagnosis and treatment of cardiac diseases.This work was partially supported by the "VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica" from the Ministerio de Economia y Competitividad of Spain (TIN2012-37546-C03-01 and TIN2011-28067) and the European Commission (European Regional Development Funds - ERDF - FEDER) and by "eTorso project" (GVA/2013-001404) from the Generalitat Valenciana (Spain). ALP is financially supported by the program "Ayudas para contratos predoctorales para la formacion de doctores" from the Ministerio de Economia y Competitividad of Spain (BES-2013-064089).López Pérez, AD.; Sebastián Aguilar, R.; Ferrero De Loma-Osorio, JM. (2015). 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Primary results of the Spanish Cryoballoon Ablation Registry: acute and long-term outcomes of the RECABA study

Cryoablation is safe and effective for the treatment of atrial fibrillation (AF) in controlled clinical trials, but contemporary real-world usage and outcomes are limited. The Report of the Spanish Cryoballoon Ablation Registry (RECABA) was designed to evaluate acute and 12-month outcomes of cryoballoon ablation for the treatment of AF in Spain. Patients from 27 Spanish centers were prospectively enrolled. Patients were treated with cryoballoon ablation and managed according to standard of care protocols at each center. The primary endpoint was ≥ 30 s freedom from AF at 12-month after a 3-month blanking period. Secondary endpoints included a description of patient characteristics, cryoablation procedural strategy and safety, and predictors of efficacy. In total, 1742 patients (71.4% PAF, 68.8% male, mean age 58.02 ± 10.40 years, 76.1% overweight or obese, CHA2DS2-VASc index 1.40 ± 1.28) were enrolled. Patients received 7.2 ± 2.67 cryo-applications. PV potentials could be detected in 61% of the PVs during ablation, with a mean time to block of 52.9 ± 37.02 s. Acute PVI was observed in 97% of PVs with 75.8% isolated with the first cryo-application. Mean procedural time was 113 ± 41 min. Acute complications occurred in 4.4% of the cases. With follow-up in 1628 patients, AF-free survival was 78.5% (PAF: 80.6% vs PersAF 73.3%; p < 0.001). Left atrium enlargement, female sex, non-PAF, and early recurrence were independent predictors of AF recurrence (p < 0.05). RECABA provides detailed insight into current dosing practices and demonstrates cryoablation is safe and effective in real-world use

Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts

[EN] Heart failure (HF) is characterized, among other factors, by a progressive loss of contractile function and by the formation of an arrhythmogenic substrate, both aspects partially related to intracellular Ca2+ cycling disorders. In failing hearts both electrophysiological and structural remodeling, including fibroblast proliferation, contribute to changes in Ca2+ handling which promote the appearance of Ca2+ alternans (Ca-alt). Ca-alt in turn give rise to repolarization alternans, which promote dispersion of repolarization and contribute to reentrant activity. The computational analysis of the incidence of Ca2+ and/or repolarization alternans under HF conditions in the presence of fibroblasts could provide a better understanding of the mechanisms leading to HF arrhythmias and contractile function disorders. Methods and findings The goal of the present study was to investigate in silico the mechanisms leading to the formation of Ca-alt in failing human ventricular myocytes and tissues with disperse fibroblast distributions. The contribution of ionic currents variability to alternans formation at the cellular level was analyzed and the results show that in normal ventricular tissue, altered Ca2+ dynamics lead to Ca-alt, which precede APD alternans and can be aggravated by the presence of fibroblasts. Electrophysiological remodeling of failing tissue alone is sufficient to develop alternans. The incidence of alternans is reduced when fibroblasts are present in failing tissue due to significantly depressed Ca2+ transients. The analysis of the underlying ionic mechanisms suggests that Ca-alt are driven by Ca2+-handling protein and Ca2+ cycling dysfunctions in the junctional sarcoplasmic reticulum and that their contribution to alternans occurrence depends on the cardiac remodeling conditions and on myocyte-fibroblast interactions. Conclusion It can thus be concluded that fibroblasts modulate the formation of Ca-alt in human ventricular tissue subjected to heart failure-related electrophysiological remodeling. Pharmacological therapies should thus consider the extent of both the electrophysiological and structural remodeling present in the failing heart.This work was partially supported by the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013 2016" from the Ministerio de Economía, Industria y Competitividad of Spain and Fondo Europeo de Desarrollo Regional (FEDER) DPI2016-75799-R (AEI/FEDER, UE), and by the Programa de Ayudas de Investigación y Desarrollo (PAID-01-17) from the Universitat Politècnica de València. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Mora-Fenoll, MT.; Gomez, JF.; Morley, G.; Ferrero De Loma-Osorio, JM.; Trenor Gomis, BA. (2019). Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts. PLoS ONE. 14(6):1-19. https://doi.org/10.1371/journal.pone.0217993S119146Glukhov, A. V., Fedorov, V. V., Kalish, P. W., Ravikumar, V. K., Lou, Q., Janks, D., … Efimov, I. R. (2012). Conduction Remodeling in Human End-Stage Nonischemic Left Ventricular Cardiomyopathy. Circulation, 125(15), 1835-1847. doi:10.1161/circulationaha.111.047274Lou, Q., Fedorov, V. V., Glukhov, A. V., Moazami, N., Fast, V. G., & Efimov, I. R. (2011). Transmural Heterogeneity and Remodeling of Ventricular Excitation-Contraction Coupling in Human Heart Failure. Circulation, 123(17), 1881-1890. doi:10.1161/circulationaha.110.989707Gomez, J. F., Cardona, K., & Trenor, B. (2015). Lessons learned from multi-scale modeling of the failing heart. Journal of Molecular and Cellular Cardiology, 89, 146-159. doi:10.1016/j.yjmcc.2015.10.016Kohl, P., & Gourdie, R. G. (2014). Fibroblast–myocyte electrotonic coupling: Does it occur in native cardiac tissue? Journal of Molecular and Cellular Cardiology, 70, 37-46. doi:10.1016/j.yjmcc.2013.12.024Gaudesius, G., Miragoli, M., Thomas, S. P., & Rohr, S. (2003). 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Circulation, 99(10), 1385-1394. doi:10.1161/01.cir.99.10.1385O’Hara, T., Virág, L., Varró, A., & Rudy, Y. (2011). Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation. PLoS Computational Biology, 7(5), e1002061. doi:10.1371/journal.pcbi.1002061Mora, M. T., Ferrero, J. M., Romero, L., & Trenor, B. (2017). Sensitivity analysis revealing the effect of modulating ionic mechanisms on calcium dynamics in simulated human heart failure. PLOS ONE, 12(11), e0187739. doi:10.1371/journal.pone.0187739Andrew MacCannell, K., Bazzazi, H., Chilton, L., Shibukawa, Y., Clark, R. B., & Giles, W. R. (2007). A Mathematical Model of Electrotonic Interactions between Ventricular Myocytes and Fibroblasts. Biophysical Journal, 92(11), 4121-4132. doi:10.1529/biophysj.106.101410Spach, M. S., Heidlage, J. F., Dolber, P. C., & Barr, R. C. (2000). Electrophysiological Effects of Remodeling Cardiac Gap Junctions and Cell Size. 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Universidad de Zaragoza. 2009. https://institutoi4.net/wp-content/uploads/2017/08/TesisEAH.pdfHeidenreich, E. A., Ferrero, J. M., Doblaré, M., & Rodríguez, J. F. (2010). Adaptive Macro Finite Elements for the Numerical Solution of Monodomain Equations in Cardiac Electrophysiology. Annals of Biomedical Engineering, 38(7), 2331-2345. doi:10.1007/s10439-010-9997-2Xie, Y., Garfinkel, A., Weiss, J. N., & Qu, Z. (2009). Cardiac alternans induced by fibroblast-myocyte coupling: mechanistic insights from computational models. American Journal of Physiology-Heart and Circulatory Physiology, 297(2), H775-H784. doi:10.1152/ajpheart.00341.2009Luo, C. H., & Rudy, Y. (1991). A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction. Circulation Research, 68(6), 1501-1526. doi:10.1161/01.res.68.6.1501Pruvot, E. J., Katra, R. P., Rosenbaum, D. S., & Laurita, K. R. (2004). 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Reduction of power line interference in electrocardiographic signals by dual Kalman filtering

[EN] This paper presents a filter for reducing powerline interference in electrocardiographic signals (ECG), based on dual parameter and state estimation using with a Kalman filter. Two models were used to represent power-line interference and ECG signal. Both models were combined to simulate the ECG signal whose state was estimated for separating the ECG signal from the interference. The proposed algorithm was fine-tuned and compared using a set of tests relying on the QT arrhythmia database. Tuning tests were done for tracking clean ECG; these results were used for setting the algorithm¿s parameters for later filtering tests. Exhaustive filtering tests were carried out on artificially corrupted database registers for given signal to noise ratios; performance curves were thus obtained, leading to comparing the proposed algorithm with other filtering methods. The proposed algorithm was compared to an recursive infinite impulse response filter (IIR) and a Kalman filter based on a simpler model. A filtering algorithm was thus obtained which is robust for changes in interference amplitude and keeps these properties for different types of ECG morphologies.[ES] En este artículo se presenta el desarrollo de un filtro para la reducción de la interferencia de línea de potencia en señales electrocardiográficas (ECG), basado en estimación dual de parámetros y de estado, empleando la filtración Kalman, en el cual se consideran modelos independientes entre la interferencia de línea de potencia y la señal ECG. Ambos modelos son combinados para simular la señal ECG medida sobre la que se realiza la estimación de estado para separar la señal de la interferencia. El algoritmo propuesto es sintonizado y comparado en un conjunto de pruebas realizadas sobre la base de datos QT de electrocardiografía. Inicialmente se hacen pruebas de sintonización del algoritmo para el rastreo de la señal ECG limpia, cuyos resultados son utilizados después para las pruebas de filtrado. Luego se llevan a cabo pruebas exhaustivas sobre la base de datos QT en la filtración de interferencia de línea de potencia, la cual ha sido introducida artificialmente en los registros, para una relación de señal a ruido (SNR) dada, obteniendo así curvas del desempeño del algoritmo, que permiten a su vez comparar con el desempeño de otros algoritmos de filtración, a saber, un filtro notch recursivo de respuesta infinita al impulso (IIR) y un filtro de Kalman, basado en un modelo más simple para la señal ECG. Como resultado, se demuestra que el algoritmo de filtrado obtenido es robusto a los cambios de amplitud de la interferencia; además, conserva sus propiedades para los diferentes tipos de morfologías de señales ECG normales y patológicas.Este trabajo se realiza en el marco del proyecto de la DIMA Técnicas de Computación de Alto Rendimiento en la Interpretación Automatizada de Imágenes Médicas y Bioseñales.Avendaño-Valencia, LD.; Avendaño, LE.; Ferrero De Loma-Osorio, JM.; Castellanos-Domínguez, G. (2007). Reducción de interferencia de línea de potencia en señales electrocardiográficas mediante el filtro dual de Kalman. Ingeniería e Investigación. 27(3):77-88. http://hdl.handle.net/10251/150636S778827

Food systems for sustainable development: Proposals for a profound four-part transformation

Evidence shows the importance of food systems for sustainable development: they are at the nexus that links food security, nutrition, and human health, the viability of ecosystems, climate change, and social justice. However, agricultural policies tend to focus on food supply, and sometimes, on mechanisms to address negative externalities. We propose an alternative. Our starting point is that agriculture and food systems' policies should be aligned to the 2030 Agenda for Sustainable Development. This calls for deep changes in comparison with the paradigms that prevailed when steering the agricultural change in the XXth century. We identify the comprehensive food systems transformation that is needed. It has four parts: first, food systems should enable all people to benefit from nutritious and healthy food. Second, they should reflect sustainable agricultural production and food value chains. Third, they should mitigate climate change and build resilience. Fourth, they should encourage a renaissance of rural territories. The implementation of the transformation relies on (i) suitable metrics to aid decision-making, (ii) synergy of policies through convergence of local and global priorities, and (iii) enhancement of development approaches that focus on territories. We build on the work of the “Milano Group,” an informal group of experts convened by the UN Secretary General in Milan in 2015. Backed by a literature review, what emerges is a strategic narrative linking climate, agriculture and food, and calling for a deep transformation of food systems at scale. This is critical for achieving the Sustainable Development Goals and the Paris Agreement. The narrative highlights the needed consistency between global actions for sustainable development and numerous local-level innovations. It emphasizes the challenge of designing differentiated paths for food systems transformation responding to local and national expectations. Scientific and operational challenges are associated with the alignment and arbitration of local action within the context of global priorities

Cardiac magnetic resonance outperforms echocardiography to predict subsequent implantable cardioverter defibrillator therapies in ST-segment elevation myocardial infarction patients

Altres ajuts: Conselleria de Educación-Generalitat Valenciana (PROMETEO/2021/008); Sociedad Española de Cardiología (Grant SEC/FEC-INVCLI 21/024)Implantable cardioverter defibrillators (ICD) are effective as a primary prevention measure of ventricular tachyarrhythmias in patients with ST-segment elevation myocardial infarction (STEMI) and depressed left ventricular ejection fraction (LVEF). The implications of using cardiac magnetic resonance (CMR) instead of echocardiography (Echo) to assess LVEF prior to the indication of ICD in this setting are unknown. We evaluated 52 STEMI patients (56.6 ± 11 years, 88.5% male) treated with ICD in primary prevention who underwent echocardiography and CMR prior to ICD implantation. ICD implantation was indicated based on the presence of heart failure and depressed LVEF (≤ 35%) by echocardiography, CMR, or both. Prediction of ICD therapies (ICD-T) during follow-up by echocardiography and CMR before ICD implantation was assessed. Compared to echocardiography, LVEF was lower by cardiac CMR (30.2 ± 9% vs. 37.4 ± 7.6%, p < 0.001). LVEF ≤ 35% was detected in 24 patients (46.2%) by Echo and in 42 (80.7%) by CMR. During a mean follow-up of 6.1 ± 4.2 years, 10 patients received appropriate ICD-T (3.16 ICD-T per 100 person-years): 5 direct shocks to treat very fast ventricular tachycardia or ventricular fibrillation, 3 effective antitachycardia pacing (ATP) for treatment of ventricular tachycardia, and 2 ineffective ATP followed by shock to treat ventricular tachycardia. Echo-LVEF ≤ 35% correctly predicted ICD-T in 4/10 (40%) patients and CMR-LVEF ≤ 35% in 10/10 (100%) patients. CMR-LVEF improved on Echo-LVEF for predicting ICD-T (area under the curve: 0.76 vs. 0.48, p = 0.04). In STEMI patients treated with ICD, assessment of LVEF by CMR outperforms Echo-LVEF to predict the subsequent use of appropriate ICD therapies

Time to –30°C as a predictor of acute success during cryoablation in patients with atrial fibrillation

Background: Freezing rate of second-generation cryoballoon (CB) is a biophysical parameter that could assist pulmonary vein isolation. The aim of this study is to assess freezing rate (time to reach –30°C ([TT-30C]) as an early predictor of acute pulmonary vein isolation using the CB. Methods: Biophysical data from CB freeze applications within a multicenter, nation-wide CB ablation registry were gathered. Successful application (SA), was defined as achieving durable intraprocedural vein isolation with time to isolation in under 60 s (SA-TTI&lt;60) as achieving durable vein isolation in under 60 s. Logistic regressions were performed and predictive models were built for the data set. Results: 12,488 CB applications from 1,733 atrial fibrillation (AF) ablation procedures were included within 27 centers from a Spanish CB AF ablation registry. SA was achieved in 6,349 of 9,178 (69.2%) total freeze applications, and SA-TTI&lt;60 was obtained in 2,673 of 4,784 (55.9%) freezes and electrogram monitoring was present. TT-30C was shorter in the SA group (33.4 ± 9.2 vs 39.3 ± 12.1 s; p &lt; 0.001) and SA-TTI&lt;60 group (31.8 ± 7.6 vs. 38.5 ± 11.5 s; p &lt; 0.001). Also, a 10 s increase in TT-30C was associated with a 41% reduction in the odds for an SA (odds ratio [OR] 0.59; 95% confidence interval [CI] 0.56–0.63) and a 57% reduction in the odds for achieving SA-TTI&lt;60 (OR 0.43; 95% CI 0.39–0.49), when corrected for electrogram visualization, vein position, and application order. Conclusions: Time to reach –30°C is an early predictor of the quality of a CB application and can be used to guide the ablation procedure even in the absence of electrogram monitoring.