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Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) allows noninvasive detection of left atrial fibrosis in patients with atrial fibrillation (AF). However, whether the same methodology can be used in the right atrium (RA) remains unknown. Our aim was to define a standardized threshold to characterize RA fibrosis in LGE-CMR.A 3 Tesla LGE-CMR was performed in 53 individuals; the RA was segmented, and the image intensity ratio (IIR) calculated for the RA wall using 1 557 767 IIR pixels (40 994±10 693 per patient). The upper limit of normality of the IIR (mean IIR+2 standard deviations) was estimated in healthy volunteers (n=9), and patients who had undergone previous typical atrial flutter ablation (n=9) were used to establish the dense scar threshold. Paroxysmal and persistent AF patients (n=10 each) were used for validation. IIR values were correlated with a high-density bipolar voltage map in 15 patients undergoing AF ablation.The upper normality limit (total fibrosis threshold) in healthy volunteers was set at an IIR = 1.21. In the postablation group, 60% of the maximum IIR pixel (dense fibrosis threshold) was calculated as IIR = 1.29. Endocardial bipolar voltage showed a weak but significant correlation with IIR. The overall accuracy between the electroanatomical map and LGE-CMR to characterize fibrosis was 56%.An IIR 1.21 was determined to be the threshold for the detection of right atrial fibrosis, while an IIR 1.29 differentiates interstitial fibrosis from dense scar. Despite differences between the left and right atria, fibrosis could be assessed with LGE-CMR using similar thresholds in both chambers.

Ventricular tachycardia (VT) substrate-based ablation has become the gold standard treatment for patients with structural heart disease-related VT. VT is linked to re-entry in relation to myocardial scarring, with areas of conduction block (core scar) and of slow conduction (border zone). Slow conduction areas can be detected in sinus rhythm as late potentials (LPs). LP abolition has been shown to be the best end point to avoid long-term recurrences. Our study aimed to analyze the challenges of LP abolition and the predictors of failure. We analyzed 169 consecutive patients with structural heart disease (61% ischemic cardiomyopathy, left ventricular ejection fraction: 37 ± 13%) who underwent VT ablation between 2013 and 2018. A preprocedural clinical evaluation, including cardiac magnetic resonance, was done in 66% of patients. Electroanatomical mapping with the identification of LPs was performed in all patients. Noninducibility was achieved in 71% (119), and complete LP abolition was achieved in 61% (103) of patients. Incomplete LP abolition was a powerful predictor of VT recurrence (67% vs 33%, hazard ratio 3.19 [2.1 to 4.7]; p0.001). Lack of use of a high-density mapping catheter (odds ratio 6.2, 1.2 to 38.1; p = 0.028), the septal substrate (odds ratio 9.34, 2.27 to 38.4; p = 0.002), and larger left ventricular mass (190 ± 58 g vs 156 ± 46 g, p = 0.002) were predictors of incomplete LP abolition. The main reasons that contributed to unsuccessful LP abolition were anatomic obstacles (such as the conduction system) and large extension of the LP area. In conclusion, incomplete LP abolition is related to VT recurrence. Lack of use of a high-density mapping catheter, the septal substrate, and larger left ventricular mass are related to incomplete LP abolition.

Objectives This study hypothesized that the shorter intrinsic PR interval observed in women allows a greater degree of fusion with intrinsic conduction, achieving a shorter QRS interval du...

BACKGROUND Substrate-based ventricular tachycardia (VT) ablation is a first-line treatment in patients with structural cardiac disease and sustained VT refractory to medical therapy. Despite technological improvements and increased knowledge of VT substrate, recurrence still is frequent. Published data are lacking on the possible reduction in VT burden after ablation despite recurrence. OBJECTIVE The purpose of this study was to assess VT burden reduction during long-term follow-up after substrate ablation and identify predictors of VT recurrence. METHODS We analyzed 234 consecutive VT ablation procedures in 207 patients (age 63 6 14.9 years; 92% male; ischemic heart disease in 65%) who underwent substrate ablation in a single center from 2013 to 2018. RESULTS After follow-up of 3.14 6 1.8 years, the VT recurrence rate was 41.4%. Overall, a 99.6% reduction in VT burden (median VT episodes per year: preprocedural 3.546 [1.347-13.951] vs postprocedural 0.001 [0-0.689]; P 5 .001) and a 96.3% decrease in implantable cardioverter-defibrillator (ICD) shocks (preprocedural 1.145 [0.118-4.467] vs postprocedural 0.042 [0-0.111] per year; P 5 .017) were observed. In the subgroup of patients who experienced VT recurrences, VT burden decreased by 69.2% (median VT episodes per year: preprocedural 2.876 [1.105-8.801] vs postprocedural 0.882 [0.505-2.283]; P ,.001). Multivariable analysis showed persistence of late potentials (67% vs 19%; hazard ratio 3.18 [2.18- 6.65]; P ,.001) and lower left ventricular ejection fraction (EF) (30 [25-40] vs 39 [30-50]; P 5 .022) as predictors of VT recurrence. CONCLUSION Despite a high recurrence rate during long-term follow-up, substrate-based VT ablation is related to a large reduction in VT burden and a decrease in ICD therapies. Lower EF and persistence of late potentials are predictors of recurrence. KEYWORDS Arrhythmic burden reduction; Implantable cardioverter-defibrillator shock prevention; Ventricular tachycardia ablation; Ventricular tachycardia recurrence predictors; Ventricular tachycardia storm; Ventricular tachycardia substrate ablation

Objectives This study sought to analyze safety and outcomes of ventricular tachycardia (VT) substrate ablation during sinus rhythm (SR), without baseline VT induction. Background Safety and outcomes after scar-related VT ablation during SR are not well known. Hemodynamic instability and need for electrical cardioversion can compromise safety of VT ablation procedures. Methods Four hundred twelve consecutive patients with structural heart disease undergoing VT ablation were included in a prospective multicenter registry. Substrate ablation during SR, without baseline VT induction, was the first step of the ablation procedure and the standard protocol. Scar dechanneling was the substrate ablation technique used. VT inducibility was tested after substrate ablation. Results VT induction protocol was negative after substrate ablation in 289 patients (70.1%), completing the procedure in SR. Procedure-related complication rate was 6.5%, including 1 death (0.2%). Thirty-day mortality after first VT ablation procedure was 1.7%. Overall survival was 95.8% and 88.6% at 1 and 3 years of follow-up, respectively. In a multivariable proportional hazards regression model, age ≥70 years (hazard ratio [HR]: 4.95 [2.59 to 9.47]; p Conclusions Substrate ablation during SR avoiding multiple VT induction has low procedure-related complications and low early mortality. Age, chronic obstructive pulmonary disease, and reduced left ventricular ejection fraction, but also incomplete substrate elimination, are predictors of mortality.

Introduction and objectives: This report presents the findings of the 2018 Spanish Catheter Ablation Registry. Methods: Data collection was retrospective. A standardized questionnaire was completed by each of the participating centers. Results: Data sent by 100 centers were analyzed, with a total number of 16,566 ablation procedures performed (the highest historically reported in this registry) for a mean of 165.5 ± 127.9 and a median of 119 procedures per center. The ablation targets most frequently treated were atrial fibrillation (n = 4234; 25.6%), atrioventricular nodal re-entrant tachycardia (n = 3525; 21.3%) and cavotricuspid isthmus (n = 3425; 20.7%). A new peak was observed in the ablation of atrial fibrillation, increasing the distance from the other substrates. The overall success rate was 91%. The rate of major complications was 2.2%, and the mortality rate was 0.04%. A total of 2.1% of the ablations were performed in pediatric patients. Conclusions: The Spanish Catheter Ablation Registry systematically and continuously enrolls the ablation procedures performed in Spain, showing a progressive increase in the number of ablations over the years, with a high success rate and low percentage of complications.

Aims: Riata® implantable cardioverter-defibrillator (ICD) leads from St. Jude Medical are prone to malfunction. This study aimed to describe the rate of this lead's malfunction in a very long-term follow-up. Methods: This single-centre observational study included 50 patients who received a Riata 7Fr dual-coil lead between 2003 and 2008. Follow-up was conducted both in person and remotely, and analysed at 8-month intervals. We evaluated the rates of cable externalization (CE), electrical failure (EF), and the interaction of these two complications. Structural lead failure was defined as radiographic CE. Oversensing of non-cardiac signal or sudden changes in impedance, sensing, or pacing thresholds constituted EF. Results: During a mean follow-up of 10.2 ± 2.9 years, 16 patients (32%) died. We observed lead malfunction in 13 patients (26%): three (23%) due to CE, six (46%) to EF and four (31%) to both complications. Of the malfunctioning leads, 77% failed after seven years of follow-up. The incidence rate (IR) of overall malfunction per 100 patients per year was 0.9 during the first seven years post-implantation, increased to 7.0 after the 7th year and more than doubled (to 16.7) after 10 years. Beyond seven years post-implantation, IR per 100 patient-years increased in both EF and CE (from 0.6 to 5.6 vs. 0.3 to 4.2, respectively). Presence of CE was associated with a 4-fold increase in the proportion of EF. Conclusion: The incidence of Riata ICD lead malfunction, both for EF and CE, increased dramatically after seven years and then more than doubled after 10 years post-implantation. Keywords: Implantable cardioverter-defibrillator, Long-term follow-up, Malfunction, Cable externalization, Electrical failure

Background: Ventricular tachycardia(VT) is caused by the presence of a slow conduction channel(CC) of border zone(BZ) tissue inside the scar-core tissue. Electroanatomic mapping can depict this tissue by voltage mapping. Areas of slow conduction can be detected as late potentials (LPs) and their abolition is the most accepted ablation endpoint. In current guidelines, bipolar voltage thresholds for BZ and core scar are 1.5 and 0.5mV respectively. The performance of these values is controversial. Purpose: To analyze the diagnostic yield of current amplitude thresholds in voltage map to define VT substrate in terms of CCs of LPs. Predictors of usefulness of current thresholds will be analyzed.Methods: All patients with structural heart disease who underwent VT ablation in Hospital Clinic in 2016-2017 were included. Maps with delineation of CCs based on LPs were created with contact-force sensor catheter. Thresholds were adjusted for every patient based on CCs. Diagnostic yield and predictors of performance of conventional thresholds were analyzed.ResultsDuring study period 57 consecutive patients were included (age:60,4+/-8,5; 50,2% ischemic cardiomyopathy, LVEF 39,8{plus minus}13.5%). Cut-off voltages that better identified the scar and BZ according LPs channels were 0,32(0,02-2 mV) and 1,84(0,3-6 mV) respectively. Current voltage thresholds identified correctly core and BZ in 87,7% and 42,1% of the patients respectively. Accuracy was worse in non-ischemic cardiomyopathy (NICM) especially for BZ (28,6% vs 55,2%,p=0,042)Conclusions: Accuracy of standard voltage thresholds for scar and BZ is poor in terms of LPs detection. Diagnostic yield is worse in NICM patients specially for border zone.

Background: Early detection of atrial fibrillation (AF) and subsequent initiation of anticoagulation and rhythm control therapy markedly reduce stroke, cardiovascular death, and heart failure, but unselected ECG screening for AF is time- and resource-intensive. Combining biomarkers reflecting different biological processes may identify patients at high risk of AF, enabling targeted ECG screening. Methods: We systematically reviewed literature and patent information to define candidate biomarkers for AF detection. The top 12 biomarkers identified through this process were quantified on a high-precision, high-throughput platform in 1485 consecutive patients at risk for AF presenting acutely to hospital (median age 69 years [Q1, Q3 60,78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. A model simultaneously considering 7 key clinical characteristics and all biomarkers was developed in a randomly sampled discovery cohort (n=933) and validated in the remaining patients (n=552). Neural networks were also applied. Findings: Using backward elimination, a model using age, sex, body mass index (BMI), BMP10, ANG2, and FGF23 discriminated between patients with and without AF with an AUC of 0·743 [95% confidence interval (CI) 0·712-0·775]. The biomarkers represent distinct pathways relevant for atrial cardiomyopathy and AF, namely hypertrophy and fibrosis (FGF23), endothelial dysfunction (ANG2), and atrial oxidative stress and the genomic predisposition to AF (BMP10). The SHAP procedure for neural networks identified the same variables as the regression. The validation yielded an AUC of 0·719 (95%CI 0·677, 0·762), corroborated using deep neural networks (AUC 0·784 [95%CI 0·745, 0·822]). Interpretation: The combination of three simple characteristics (age, sex, BMI) and three biomarkers (BMP10, ANG2, and FGF23) robustly identifies patients with AF. Such an approach enables targeted screening for AF and provides a platform to develop personalised prevention and treatment in patients with AF. Funding Statement: This work was partially supported by the European Commission (grant agreements no. 633196 [CATCH ME]) to PKi, LF, BC, SH, SK, LM, MFS, US, and no. 116074 [BigData@Heart EU IMI] to PKi, British Heart Foundation (FS/13/43/30324 and (AA/18/2/34218) to PKi and LF), German Centre for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK, via a grant to AFNET to PKi), and Leducq Foundation (14CVD01) to PKi. Declaration of Interests: LF has received institutional research grants and non-financial support from European Union, British Heart Foundation, Medical Research Council (UK), and DFG and Gilead. PKi has received additional support for research from the European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK), and German Centre for Heart Research, from several drug and device companies active in atrial fibrillation, honoraria from several such companies. PKi and LF are listed as inventors on two patents held by University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). PKa is an employee of Roche Diagnostics GmbH. AZ is an employee of Roche Diagnostics Intl. All other authors have reported no relationships relevant to the contents of this paper to disclose. Ethics Approval Statement: This study complied with the Declaration of Helsinki, was approved by the National Research Ethics Service Committee (IRAS ID 97753), and was sponsored by the University of Birmingham.

Objectives The aim of this study was to compare patient response to cardiac resynchronization therapy (CRT) using fusion-optimized atrioventricular (AV) and interventricular (VV) intervals versus nominal settings. Background The additional benefit obtained by AV- and VV-interval optimization in patients undergoing CRT remains controversial. Previous studies show short-term benefit in hemodynamic parameters; however, midterm randomized comparison between electrocardiogram optimization and nominal parameters is lacking. Methods A group of 180 consecutive patients with left bundle branch block treated with CRT were randomized to fusion-optimized intervals (FOI) or nominal settings. In the FOI group, AV and VV intervals were optimized according to the narrowest QRS, using fusion with intrinsic conduction. Clinical response was defined as an increase >10% in the 6-min walk test or an increment of 1 step in New York Heart Association functional class. The left ventricular (LV) remodeling was defined as >15% decrease in left ventricular end-systolic volume (LVESV) at 12-month follow-up. Additionally, patients with LVESV reduction >30% relative to baseline were considered super-responders; by contrast, negative responders had increased LVESV relative to baseline. Results Participant characteristics included a mean age of 65 ± 10 years, 68% male, 37% with ischemic cardiomyopathy, LV ejection fraction 26 ± 7%, and QRS 180 ± 22 ms. Baseline QRS was shortened significantly more by FOI, compared with nominal settings (−56.55 ± 17.65 ms vs. −37.81 ± 22.07 ms, respectively; p = 0.025). At 12 months, LV reverse remodeling was achieved in a larger proportion of the FOI group (74% vs. 53% [odds ratio: 2.02 (95% confidence interval: 1.08 to 3.76)], respectively; p = 0.026). No significant differences were observed in clinical response (61% vs. 53% [odds ratio: 1.43 (95% confidence interval: 0.79 to 2.59)], respectively; p = 0.24). Conclusions Device optimization based on FOI achieves greater LV remodeling, compared with nominal settings. (ECG Optimization of CRT: Evaluation of Mid-Term Response [BEST]; NCT01439529)

Objectives This study sought to understand and characterize the acute atrial response to endurance exercise and the influence of the amount of exercise performed. Background Endurance exercise seems to be recognized as a risk factor for developing atrial arrhythmia. Atrial geometrical and functional remodeling may be the underlying substrate. Methods Echocardiography was performed in 55 healthy adults at baseline and after a 3-stage trail race: a short race (S) (14 km), n = 17; a medium race (M) (35 km), n = 21; and a long race (L) (56 km), n = 17. Analysis consisted of standard, speckle-tracking assessment of both the left ventricle (LV) and right ventricle (RV) and both the left atrium (LA) and the right atrium (RA): a-wave strain (Sa) and strain rate (Ra) as a surrogate for atrial contractile function and s-wave strain (St) and strain rate (SR) as reservoir function. Results After the race, RA reservoir function decreased in group M (Δ% SRs: −12.5) and further in group L (Δ% SRs: −15.4), with no changes in group S. RA contractile function decreased in group L (Δ% SRa: −9.3), showed no changes in group M (Δ% SRa: +0.7), and increased in group S (Δ% SRa: +14.8). A similar trend was documented in LA reservoir and contractile function but with less pronounced changes. The decrease in RA reservoir after the race correlated with the decrease in RV global longitudinal strain (GLS) (Δ% RVGLS vs. RASt and RASRs: +0.44; p Conclusions During a trail-running race, an acute exercise-dose dependent impairment in atrial function was observed, mostly in the RA, which was related to RV systolic dysfunction. The impact on atrial function of long-term endurance training might lead to atrial remodeling, favoring arrhythmia development.

Objectives: The goal of this study was to assess mechanisms underlying atrial fibrillation (AF) promotion by exercise training in an animal model.Background: High-level exercise training promotes A...

Introduction and objectives The outcomes of atrial fibrillation ablation procedures vary widely between different centers. Our objective was to analyze the results and complications of this procedure in our center and identify factors predicting the efficacy and safety of atrial fibrillation ablation. Methods In total, 726 atrial fibrillation ablation procedures were performed in our center between 2002 and 2009. Beginning in January 2008, a protocol for anticoagulation and conscious sedation was systematically applied. Outcomes and complications could therefore be compared in 2 well-differentiated groups: group A included 419 procedures performed prior to 2008 and group B included 307 procedures completed after 2008 using the new protocol. Results During an average follow-up of 8.7 months, 60.9% of patients were arrhythmia-free after one or repeat procedures. After only 1 procedure, the success rate was 41% and significantly higher in group B (51.6% vs 35.2% in group A; P =.001). There were 31 major complications (4.2%), 26 in group A (6.2%) and 5 in group B (1.6%) ( P =.002). The implementation of the new protocol was an independent predictor of the absence of complications (odds ratio=0.406; 95% confidence interval, 0.214-0.769; P Conclusions Systematic application of an anticoagulation and conscious sedation protocol is associated with improved results and fewer complications of atrial fibrillation ablation. Factors not evaluated in the present study, such as operator experience and ongoing improvements in atrial fibrillation ablation technology, could have influenced these findings.

Resumen Introduccion y objetivos Los resultados y las complicaciones del procedimiento de ablacion de fibrilacion auricular varian ampliamente entre los diferentes centros. Nuestro objetivo es analizar los resultados y las complicaciones derivadas de este procedimiento en nuestro centro e identificar los factores predictores de exito y de seguridad. Metodos Entre 2002 y 2009 se realizo un total de 726 procedimientos de ablacion de fibrilacion auricular. Basandonos en la aplicacion sistematica de un protocolo de anticoagulacion y sedacion consciente desde enero 2008, podemos establecer dos estrategias de ablacion que constituyen dos grupos bien diferenciados: grupo A, constituido por 419 procedimientos realizados antes de enero 2008, y grupo B, formado por 307 procedimientos realizados despues. Resultados El 60,9% de los pacientes no presentaron recurrencia arritmica tras varios procedimientos durante un seguimiento medio de 8,7 meses. Con un unico procedimiento, la tasa total de exito fue del 41%, significativamente mayor entre los pacientes del grupo B (el 51,6 frente al 35,2% de exito en el grupo A; p = 0,001). Hubo un total de 31 complicaciones mayores (4,2%); 26 en el grupo A (6,2%) y 5 en el grupo B (1,6%) (p = 0,002). La protocolizacion del procedimiento fue un factor predictor de la ausencia de complicaciones (odds ratio = 0,406; intervalo de confianza del 95%, 0,214-0,769; p Conclusiones La aplicacion sistematica de un protocolo de anticoagulacion y sedacion consciente se asocia a la mejora de los resultados y la reduccion de las complicaciones en el procedimiento de ablacion de fibrilacion auricular. Otros factores no evaluados en este estudio, como la curva de aprendizaje de los operadores y la progresiva mejora tecnologica, pueden haber influido en los cambios observados.

Introduction and objectives: High endothelin-1 (ET-1) levels have been linked to poor clinical outcomes after ST-segment elevation myocardial infarction (STEMI). Vasoconstriction of the coronary microcirculation seems to be the underlying mechanism. The aim of the study was to assess the effect of ET-1 on microvascular integrity, infarct size, left ventricular ejection fraction (LVEF) and myocardial salvage in evolving myocardial infarction (MI). Methods: We measured ET-1 levels acutely (6-24 h) in 127 patients presenting with their first STEMI. Contrast-enhanced cardiac magnetic resonance (ce-CMR) was performed in 94 patients within 1 week to assess microvascular obstruction (MO), infarct size and LVEF. A myocardial salvage index (MSI) was defined as the percentage of at-risk angiographic area without necrosis on the ce-CMR. Results: Mean age was 60.9 11.8 years and 98 (77%) were males. Median ET-1 level within the first 24 h was 6.8 pg/mL (25 th –75 th percentile range: 5.4–8.5 pg/mL). Patients with ET-1 concentrations over the median presented higher percentage of MO (77.7% for ET-1 > 6.8 pg/mL vs. 16.6% for ET-1 6.8 pg/mL, P 6.8 pg/mL vs. 37.4 (26%) for ET-1 6.8 pg/mL, P = .02). ET-1 levels did not show a significant association with infarct size (P = .11) and LVEF (P = .16). Multivariate analysis found ET-1 to be a significant predictor of MO (OR = 2.78; CI 95% 1.16-6.66; P = .021) and MSI Percentile 25 (OR = 1.69, CI 95% 1.01-2.81; P = .04). Conclusions: High ET-1 levels after myocardial infarction are associated with the presence of microvascular obstruction and lower myocardial salvage index.

Indications for percutaneous coronary intervention with stent placement are increasing; some candidates already require oral anticoagulation. Safety of triple antithrombotic therapy — aspirin (ASA), clopidogrel and oral anticoagulation (OAC) — remains largely unknown. In order to study hemorrhagic complications in those patients, we identified thirty-three patients from our anticoagulation clinic registry who were prescribed triple antithrombotic therapy. All hemorrhagic events were collected and classified as non-severe (NSH) or severe (SH). The same population provided a control to determine increased risk from addition of a second antiplatelet drug. Overall, patients were followed for 53 patient-months while on triple therapy (TT) and 869 patient-months on double therapy. Patients in TT group had more hemorrhages (90.6% patient-years vs 8.29% patient-years, p p

Early repolarization, involving ST-segment elevation and, sometimes, prominent J waves at the QRS-ST junction, has been considered a normal electrocardiographic variant for over 60 years. A growing number of case reports and case-control studies indicate that in some instances, early repolarization patterns are associated with increased risk of idiopathic ventricular fibrillation. Epidemiological evidence indicates a dose effect for the risk of cardiac and sudden death with the extent of J-point elevation. This paper reviews present knowledge regarding the epidemiology, presentation, therapeutic response, and mechanisms characteristic of early repolarization. We highlight major unanswered questions relating to our limited ability to determine which individuals with this common electrocardiographic variant are at risk for sudden death, our incomplete understanding of underlying mechanisms, the inadequate information regarding genetic determinants and therapeutic responses, and the unclear relationship between early repolarization and other conditions involving accelerated repolarization and sudden arrhythmic death such as Brugada and short-QT syndromes. This review paper intends to inform the practicing physician about important clinical issues and to stimulate investigators to address the many unresolved questions in this rapidly evolving field.

Los farmacos antiarritmicos con selectividad auricular actuan de forma preferente modificando determinadas caracteristicas electrofisiologicas de las auriculas y minimizando el riesgo arritmogenico en los ventriculos. Se ha demostrado que la ranolazina, un farmaco utilizado para el tratamiento de la angina estable, bloquea muy selectivamente los canales de sodio de la auricula y, en concreto, su corriente rapida (IKr). El bloqueo de IKr tambien interviene con las dosis usadas habitualmente, y es posible el bloqueo multicanal. Ambos efectos consiguen reducir, experimentalmente in vitro e in vivo, las caracteristicas que precipitan y mantienen determinadas arritmias, especialmente la fibrilacion auricular. Asimismo se ha senalado, por el bloqueo de INaL en el ventriculo, una reduccion de arritmias ventriculares en distintos modelos con prolongacion de la repolarizacion y susceptibilidad a la aparicion de taquicardias ventriculares helicoidales. A pesar de eso, la evidencia clinica para su uso en arritmias auriculares y ventriculares es aun escasa y basada solamente en un subestudio y en su uso en casos aislados, por lo que son precisos estudios aleatorizados y controlados a mayor escala y disenados a este fin.

We appreciate the positive comments from Dr. Bhatti and colleagues regarding our observations in a high-intensity endurance-exercise rat model [(1)][1]. They point out the consistency between our findings and clinical observations, and discuss evidence related to the mechanisms that we uncovered.