Cardiac Pulsed Field Ablation Lesion Durability Assessed by Polarization-Sensitive Optical Coherence Reflectometry.

BACKGROUND: Pulsed field ablation uses electrical fields to cause nonthermal cell death over several hours. Polarization-sensitive optical coherence reflectometry is an optical imaging technique that can detect changes in the tissue ultrastructure in real time, which occurs when muscular tissue is damaged. The objective of this study was to evaluate the ability of a polarization-sensitive optical coherence reflectometry system to predict the development of chronic lesions based on acute changes in tissue birefringence during pulsed field ablation. METHODS: Superior vena cava isolation was performed in 30 swine using a biphasic, bipolar pulsed field ablation system delivered with a nonirrigated focal tip catheter. Acute changes in tissue birefringence and voltage abatement were analyzed for each individual lesion. A high-resolution electroanatomical map was performed at baseline and 4 to 12 weeks after ablation to locate electrical gaps in the ablated area. RESULTS: A total of 141 lesions were delivered and included in the analysis. Acute electrical isolation based on the electroanatomical map was achieved in 96% of the animals, but chronic isolation was only seen in 14 animals (46%). The mean voltage abatement of lesions that showed recovery was 82.8%±14.6% versus 84.4%±17.4% for those that showed fibrosis (P=0.7). The mean acute reduction in tissue birefringence in points demonstrating fibrosis was 63.8%±11.3% versus 9.1%±0.1% in the points that resulted in electrical gaps. A threshold of acute reduction of birefringence of ≥20% could predict chronic lesion formation with a sensitivity of 96% and a specificity of 83%. CONCLUSIONS: Acute tissue birefringence changes assessed with polarization-sensitive optical coherence reflectometry during pulsed field ablation can predict chronic lesion formation and guide the ablation procedure although limited by the tissue thickness.

Metabolomics of Red Wines Aged Traditionally, with Chips or Staves.

Traditionally and alternatively aged wines' odour activity values (OAVs) are investigated to differentiate and highlight the differences between the selected methods. An analysis of the volatile aroma compounds of wines derived from ageing in barrels, oak chips, and staves was performed using stir bar sorptive extraction chromatography-mass spectroscopy (SBSE-GC-MS). The results showed that alcohols, esters, and oak compounds were the main contributors to aroma, and their OAVs were higher in the stave samples after 3 months than in the samples from the other two systems of ageing. Furthermore, wines aged with staves have stronger fruity, spiced, and woody aromas, while samples aged in barrels present more chemistry-driven, floral, caramelly, and creamy aromas. The staves-medium plus toast (SMPT at 3 months > 225) and chips-medium plus toast (CMPT at 3 months > 170) showed the highest levels of aromatic series, suggesting that alternative systems provided more powerful aromas than traditional systems, such as barrels-medium plus toast (BMPT at 3 months > 150). A principal component analysis (PCA), orthogonal partial least squares (OPLS) analysis, and cluster analysis allowed for a clear differentiation to be made between red wines according to ageing systems and ageing times. The odour activity values fingerprint in winemaking is a feasible approach to characterise and distinguish wines. Moreover, OAVs provide important information on the effects of production methods on wine quality and aroma profile.

Conduction system pacing and atrioventricular node ablation in heart failure: The PACE-FIB study design.

AIMS: Atrial fibrillation (AF) worsens the prognosis of patients with heart failure (HF). Successful treatments are still very scarce for those with permanent AF and preserved (HFpEF) or mildly reduced (HFmrEF) ejection fraction. In this study, the long-term benefits and safety profile of heart rate regularization through left-bundle branch pacing (LBBP) and atrioventricular node ablation (AVNA) will be explored in comparison with pharmacological rate-control strategy. METHODS AND RESULTS: The PACE-FIB trial is a multicentre, prospective, open-label, randomized (1:1) clinical study that will take place between March 2022 and February 2027. A total of 334 patients with HFpEF/HFmrEF and permanent AF will receive either LBBP followed by AVNA (intervention arm) or optimal pharmacological treatment for heart rate control according to European guideline recommendations (control arm). All patients will be followed up for a minimum of 36 months. The primary outcome measure will be the composite of all-cause mortality, HF hospitalization, and worsening HF at 36 months. Other secondary efficacy and safety outcome measures such as echocardiographic parameters, functional status, and treatment-related adverse events, among others, will be analysed too. CONCLUSION: LBBP is a promising stimulation mode that may foster the clinical benefit of heart rate regularization through AV node ablation compared with pharmacological rate control. This is the first randomized trial specifically addressing the long-term efficacy and safety of this pace-and-ablate strategy in patients with HFpEF/HFmrEF and permanent AF.

Long-term prognosis and emergency management for patients with an implantable cardioverter defibrillator: the EMERGE-ICD study. / Estudio EMERG-ICD: manejo y pronóstico a largo plazo de las urgencias en los pacientes portadores de un desfibrilador automático implantable.

OBJECTIVES: Patients with implantable cardioverter defibrillators (ICDs) are at risk of serious complications that are often treated in hospital emergency departments (EDs). The EMERG-ICD study (Emergency Department Management and Long-term Prognosis for Patients with ICDs) analysed management and long-term prognosis of ED patients with an ICD after an acute clinical event. MATERIAL AND METHODS: Observational multicenter cohort study including consecutive adult patients with ICDs who came to 27 hospital EDs in Spain for treatment and were followed for 10 years. We collected clinical variables on presentation, ED case management variables, and the date and cause of death in each case. The primary outcome variable was all-cause mortality. RESULTS: Five-hundred three patients were studied; 471 had structural heart disease (SHD) and 32 had primary electrical heart disease (PEHD). Beta-blockers were prescribed in the ED for 55% of the patients for whom they were indicated. Twenty-four (4.8%), 75 (15.7%), and 368 (73.2%) patients died during follow-up at 1 month, 1 year, and 10 years, respectively. Of these, 363 (77.1%) had SHD and 5 (15.6%) had PEHD (hazard ratio, 8.05 (95% CI, 3.33- 19.46). Among patients with SHD, the cause of death was cardiovascular in 66%. Mortality correlated significantly with seeking care for cardiovascular symptoms, advanced age, male sex, diabetes, a New York Heart Association score of 2 or more, severe ventricular dysfunction, and long-term amiodarone therapy. CONCLUSION: Prognosis after an acute clinical event is poor in patients with SHD and ICDs, mainly due to cardiovascular causes, especially among patients with associated comorbidities and cardiovascular complaints. Mortality is lower in patients with PEHD.

OBJETIVO: Los pacientes portadores de desfibriladores automáticos implantables (DAI) tienen riesgo de complicaciones graves que son atendidas con frecuencia en los servicios de urgencias hospitalarios (SUH). Este estudio analiza el manejo y el pronóstico de las urgencias en portadores de un DAI. METODO: Estudio de cohorte observacional y multicéntrico que incluyó de manera consecutiva pacientes adultos portadores de DAI que consultaron en 27 SUH en España, con seguimiento posterior a 10 años. Se recogieron las variables clínicas, manejo en el SUH, fecha y causa del fallecimiento. La variable de resultado primaria fue la mortalidad por cualquier causa. RESULTADOS: Se incluyeron 503 pacientes, 471 con cardiopatía estructural (CE) y 32 con enfermedad eléctrica primaria cardiaca (EEPC). Se prescribió betabloqueantes en el SUH al 55% de los pacientes con indicación. Durante el seguimiento fallecieron 24 (4,8%), 75 (15,7%) y 368 pacientes (73,2%) a 1 mes, 1 año y 10 años, respectivamente. De estos, 363 tenían CE y 5 EEPC (77,1% vs 15,6%, HR 8,05 IC 95% 3,33-19,46). Entre los pacientes con CE, la mortalidad global fue de causa cardiovascular en el 66% de los casos. La mortalidad se asoció significativamente con la consulta por una causa cardiovascular, edad avanzada, sexo masculino, diabetes, NHYA 2, disfunción ventricular grave y tratamiento crónico con amiodarona. CONCLUSIONES: El pronóstico de los portadores de DAI con CE es muy adverso, fundamentalmente debido a complicaciones cardiovasculares en pacientes con comorbilidades que consultan por sintomatología cardiovascular. La mortalidad es menor en los pacientes con EEPC.

Repeat cryoablation as a redo procedure for atrial fibrillation ablation: Is it a good choice?

BACKGROUND: Ablation of atrial fibrillation (AF), both cryoablation ablation (CBA) and radiofrequency catheter ablation (RFCA), have demonstrated to be safe and effective. About 1 in 3 patients may face a redo due to recurrence and the best technique is unknown. The aim of this study is to assess the efficacy of CBA as a repeat procedure in patients with prior CBA or RFCA. METHODS: A nation-wide CBA registry (RECABA) was analyzed and patients were compared who had previously undergone CBA (Prior-CB) or RFCA (Prior-RF). The primary endpoint was AF recurrence at 12 months after a 3-month blanking period. A survival analysis was performed, univariate and multivariate Cox models were also built. RESULTS: Seventy-four patients were included. Thirty-three (44.6%) were in the Prior-CB group and 41 (55.4%) in the Prior-RF. There were more reconnected pulmonary veins in the Prior-RF than in Prior-CB group (40.4% vs.16.5%, p = 0.0001). The 12-month Kaplan-Meier estimate of freedom from AF recurrence after the blanking period was 61.0% (95% confidence interval [CI] 41.4-75.8%) in the Prior-CB, and 89.2% (95% CI 73.6-95.9%) in the Prior-RF group (p = 0.002). Multivariate Cox regression pointed Prior-CB as the sole independent predictor of AF recurrence, with an adjusted HR of 2.67 (95% CI 1.05-6.79). CONCLUSIONS: Repeat CBA shows higher rates of AF recurrences compared to CBA after a previous RFCA despite presenting less reconnected veins at the procedure. These data suggest that patients with AF recurrence after CBA may benefit from other ablation techniques after a recurrence. RECABA is registered at clinicaltrials.gov with the Unique Identifier NCT02785991.

Efficacy and safety of the extraction of cardiostimulation leads using a mechanical dissection tool. A single center experience.

BACKGROUND: The percutaneous extraction of endovascular cardiostimulation and defibrillation leads is the most frequent technique nowadays. The tools used today must guarantee the success of the procedure, with the minimum of complications. Our objective was to analyze the safety and efficacy of lead extraction using the Evolution mechanical dissection tool (Cook Medical, USA). METHODS: A retrospective study was carried out in a total of 826 consecutive patients from October 2009 to December 2018 who underwent the procedure with the Evolution mechanical dissection tool. Preoperative study included complete blood tests, echocardiogram, and chest X-ray. The procedures were performed in the operating room, under general anesthesia and echocardiographic control. RESULTS: A total of 1227 leads were extracted with a mean chronicity of 10.3 ± 5.1 years. Clinical success (CS) rate was 99.7%. A total of 16 (1.9%) complications occurred, 2 (0.24%) were major complications and 14 (1.7%) were minor complications. There was no operative mortality. There was no statistically significant relationship between implant chamber and complete efficacy. The complete extraction was achieved in all left ventricular leads, in 762 of 774 (98.45%) of right ventricular lead removal, and in 330 of 334 (98.8%) of right atrial leads (p = .31). CONCLUSION: In our experience, percutaneous extraction of intravenous leads via the use of the Evolution tool (Cook Medical, USA), is a very effective and safe technique that offers low morbidity and mortality.

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. And SA with time to isolation under 60 s (SA-TTI<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<60 was obtained in 2,673 of 4,784 (55.9%) freezes where electrogram monitoring was present. TT-30C was shorter in the SA group (33.4 ± 9.2 vs 39.3 ± 12.1 s; p < 0.001) and SA-TTI<60 group (31.8 ± 7.6 vs. 38.5 ± 11.5 s; p < 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<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.

Mindfulness-based emotional regulation for patients with implantable cardioverter-defibrillators: A randomized pilot study of efficacy, applicability, and safety.

BACKGROUND: The efficacy of mindfulness-based interventions to reduce anxiety or improve quality of life (QoL) in patients with cardiac pathologies is well established. However, there is scarce information on the efficacy, applicability, and safety of these interventions in adult patients with an implantable cardioverter-defibrillator (ICD). In this study, we examined their efficacy on QoL, psychological and biomedical variables, as well as the applicability and safety of a mindfulness-based intervention in patients with an ICD. METHODS: Ninety-six patients with an ICD were randomized into two intervention groups and a control group. The interventions involved training in mindfulness-based emotional regulation, either face-to- -face or using the "REM Volver a casa" mobile phone application (app). RESULTS: The sample presented medium-high QoL baseline scores (mean: 68), low anxiety (6.84) and depression (3.89), average mindfulness disposition (128), and cardiological parameters similar to other ICD populations. After the intervention, no significant differences were found in the variables studied between the intervention and control groups. Retention was average (59%), and there were no adverse effects due to the intervention. CONCLUSIONS: After training in mindfulness-based emotional regulation (face-to-face or via app), no significant differences were found in the QoL or psychological or biomedical variables in patients with an ICD. The intervention proved to be safe, with 59% retention.

Cryoballoon Ablation for Persistent and Paroxysmal Atrial Fibrillation: Procedural Differences and Results from the Spanish Registry (RECABA).

Introduction: Cryoballoon ablation (CBA) has become a standard treatment for paroxysmal atrial fibrillation (PaAF) but limited data is available for outcomes in patients with persistent atrial fibrillation (PeAF). Methods: We analyzed the first 944 patients included in the Spanish Prospective Multi-center Observation Post-market Registry to compare characteristics and outcomes of patients undergoing CBA for PeAF versus PaAF. Results: A total of 944 patients (57.8 ± 10.4 years; 70.1% male) with AF (27.9% persistent) were prospectively included from 25 centers. PeAF patients were more likely to have structural heart disease (67.7 vs. 11.4%; p < 0.001) and left atrium dilation (72.6 vs. 43.3%; p < 0.001). CBA of PeAF was less likely to be performed under general anesthesia (10.7 vs. 22.2%; p < 0.001), with an arterial line (32.2 vs. 44.6%; p < 0.001) and assisted transeptal puncture (11.9 vs. 17.9%; p = 0.025). During an application, PeAF patients had a longer time to −30 °C (35.91 ± 14.20 vs. 34.93 ± 12.87 s; p = 0.021) and a colder balloon nadir temperature during vein isolation (−35.04 ± 9.58 vs. −33.61 ± 10.32 °C; p = 0.004), but received fewer bonus freeze applications (30.7 vs. 41.1%; p < 0.001). There were no differences in acute pulmonary vein isolation and procedure-related complications. Overall, 76.7% of patients were free from AF recurrences at 15-month follow-up (78.9% in PaAF vs. 70.9% in PeAF; p = 0.09). Conclusions: Patients with PeAF have a more diseased substrate, and CBA procedures performed in such patients were more simplified, although longer/colder freeze applications were often applied. The acute efficacy/safety profile of CBA was similar between PaAF and PeAF patients, but long-term results were better in PaAF patients.

Tbx5 variants disrupt Nav1.5 function differently in patients diagnosed with Brugada or Long QT Syndrome.

AIMS: The transcription factor Tbx5 controls cardiogenesis and drives Scn5a expression in mice. We have identified two variants in TBX5 encoding p. D111Y and p. F206L Tbx5, respectively, in two unrelated patients with structurally normal hearts diagnosed with long QT (LQTS) and Brugada (BrS) syndrome. Here, we characterized the consequences of each variant to unravel the underlying disease mechanisms. METHODS AND RESULTS: We combined clinical analysis with in vivo and in vitro electrophysiological and molecular techniques in human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs), HL-1 cells, and cardiomyocytes from mice trans-expressing human wild-type (WT) or mutant proteins. Tbx5 increased transcription of SCN5A encoding cardiac Nav1.5 channels, while repressing CAMK2D and SPTBN4 genes encoding Ca/calmodulin kinase IIδ (CaMKIIδ) and ßIV-spectrin, respectively. These effects significantly increased Na current (INa) in hiPSC-CMs and in cardiomyocytes from mice trans-expressing Tbx5. Consequently, action potential (AP) amplitudes increased and QRS interval narrowed in the mouse electrocardiogram. p. F206L Tbx5 bound to the SCN5A promoter failed to transactivate it, thus precluding the pro-transcriptional effect of WT Tbx5. Therefore, p. F206L markedly decreased INa in hiPSC-CM, HL-1 cells and mouse cardiomyocytes. The INa decrease in p. F206L trans-expressing mice translated into QRS widening and increased flecainide sensitivity. p. D111Y Tbx5 increased SCN5A expression but failed to repress CAMK2D and SPTBN4. The increased CaMKIIδ and ßIV-spectrin significantly augmented the late component of INa (INaL) which, in turn, significantly prolonged AP duration in both hiPSC-CMs and mouse cardiomyocytes. Ranolazine, a selective INaL inhibitor, eliminated the QT and QTc intervals prolongation seen in p. D111Y trans-expressing mice. CONCLUSIONS: In addition to peak INa, Tbx5 critically regulates INaL and the duration of repolarization in human cardiomyocytes. Our original results suggest that TBX5 variants associate with and modulate the intensity of the electrical phenotype in LQTS and BrS patients.

Time-efficient three-dimensional transmural scar assessment provides relevant substrate characterization for ventricular tachycardia features and long-term recurrences in ischemic cardiomyopathy.

Delayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging requires novel and time-efficient approaches to characterize the myocardial substrate associated with ventricular arrhythmia in patients with ischemic cardiomyopathy. Using a translational approach in pigs and patients with established myocardial infarction, we tested and validated a novel 3D methodology to assess ventricular scar using custom transmural criteria and a semiautomatic approach to obtain transmural scar maps in ventricular models reconstructed from both 3D-acquired and 3D-upsampled-2D-acquired LGE-CMR images. The results showed that 3D-upsampled models from 2D LGE-CMR images provided a time-efficient alternative to 3D-acquired sequences to assess the myocardial substrate associated with ischemic cardiomyopathy. Scar assessment from 2D-LGE-CMR sequences using 3D-upsampled models was superior to conventional 2D assessment to identify scar sizes associated with the cycle length of spontaneous ventricular tachycardia episodes and long-term ventricular tachycardia recurrences after catheter ablation. This novel methodology may represent an efficient approach in clinical practice after manual or automatic segmentation of myocardial borders in a small number of conventional 2D LGE-CMR slices and automatic scar detection.

Towards a better understanding of the evolution of odour-active compounds and the aroma perception of sparkling wines during ageing.

A native veil-forming yeast and a commercial yeast strain were used to elaborate sparkling wines by the Champenoise method with a grape variety traditionally used for the production of still wines. Wines aged on lees for fifteen months were sampled at five points and their physicochemical and sensory indices were analysed. Unsupervised and supervised statistical techniques were used to establish a comparison between 81 volatile compounds and eight odour descriptors (chemical, fruity, floral, fatty, balsamic, vegetal, empyreumatic and spicy). Principal component analysis of both datasets showed good separation among the samples in relation to ageing time and yeast strain. By using a partial least squares regression-based criterion, 38 odour active compounds were selected as the most influential for the ageing factor and out of them, only 27 were unique to certain aroma descriptors. These results contribute to a better understanding of the aroma perception of sparkling wines.

Identification of patients at risk of sudden cardiac death in congenital heart disease: The PRospEctiVE study on implaNTable cardIOverter defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease (PREVENTION-ACHD).

BACKGROUND: Sudden cardiac death (SCD) is the main preventable cause of death in patients with adult congenital heart disease (ACHD). Since robust risk stratification methods are lacking, we developed a risk score model to predict SCD in patients with ACHD: the PRospEctiVE study on implaNTable cardIOverter defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease (PREVENTION-ACHD) risk score model. OBJECTIVE: The purpose of this study was to prospectively study predicted SCD risk using the PREVENTION-ACHD risk score model and actual SCD and sustained ventricular tachycardia/ventricular fibrillation (VT/VF) rates in patients with ACHD. METHODS: The PREVENTION-ACHD risk score model assigns 1 point each to coronary artery disease, New York Heart Association class II/III heart failure, supraventricular tachycardia, systemic ejection fraction < 40%, subpulmonary ejection fraction < 40%, QRS duration ≥ 120 ms, and QT dispersion ≥ 70 ms. SCD risk was calculated for each patient. An annual predicted risk of ≥3% constituted high risk. The primary outcome was SCD or VT/VF after 2 years. The secondary outcome was SCD. RESULTS: The study included 783 consecutive patients with ACHD (n=239 (31%) left-sided lesions; n=138 (18%) tetralogy of Fallot; n=108 (14%) closed atrial septal defect; median age 36 years; interquartile range 28-47 years; n=401 (51%) men). The PREVENTION-ACHD risk score model identified 58 high-risk patients. Eight patients (4 at high risk) experienced the primary outcome. The Kaplan-Meier estimates were 7% (95% confidence interval [CI] 0.1%-13.3%) in the high-risk group and 0.6% (95% CI 0.0%-1.1%) in the low-risk group (hazard ratio 12.5; 95% CI 3.1-50.9; P < .001). The risk score model's sensitivity was 0.5 and specificity 0.93, resulting in a C-statistic of 0.75 (95% CI 0.57-0.90). The hazard ratio for SCD was 12.4 (95% CI 1.8-88.1) (P = .01); the sensitivity and specificity were 0.5 and 0.92, and the C-statistic was 0.81 (95% CI 0.67-0.95). CONCLUSION: The PREVENTION-ACHD risk score model provides greater accuracy in SCD or VT/VF risk stratification as compared with current guideline indications and identifies patients with ACHD who may benefit from preventive implantable cardioverter-defibrillator implantation.

Using an electronic nose and volatilome analysis to differentiate sparkling wines obtained under different conditions of temperature, ageing time and yeast formats.

Effect of yeast inoculation format (F), temperature (T), and "on lees" ageing time (t) factors were evaluated on the composition of sparkling wines by a quantitative fingerprint obtained from volatile metabolites and the response of an electronic nose (E-nose). Wines elaborated according the traditional method at 10 and 14 °C, free cells and yeast biocapsules formats were monitored at 15 and 24 months of ageing time. Sixty-six volatiles identified and quantified in the eight sampling lots were subjected to a pattern recognition technique. A dual criterion based on univariate (ANOVA) and multivariate analysis (PLS-DA) through the variable importance projection (VIP) values, allowed to identify ten volatiles as potential markers for T factor, eleven for t and twelve for F factors. The discriminant models based on E-nose dataset enable a 100% correct classification of samples, in relation with t and F factors and the 83% for T factor.

Predicting sudden cardiac death in adults with congenital heart disease.

OBJECTIVES: To develop, calibrate, test and validate a logistic regression model for accurate risk prediction of sudden cardiac death (SCD) and non-fatal sudden cardiac arrest (SCA) in adults with congenital heart disease (ACHD), based on baseline lesion-specific risk stratification and individual's characteristics, to guide primary prevention strategies. METHODS: We combined data from a single-centre cohort of 3311 consecutive ACHD patients (50% male) at 25-year follow-up with 71 events (53 SCD and 18 non-fatal SCA) and a multicentre case-control group with 207 cases (110 SCD and 97 non-fatal SCA) and 2287 consecutive controls (50% males). Cumulative incidences of events up to 20 years for specific lesions were determined in the prospective cohort. Risk model and its 5-year risk predictions were derived by logistic regression modelling, using separate development (18 centres: 144 cases and 1501 controls) and validation (two centres: 63 cases and 786 controls) datasets. RESULTS: According to the combined SCD/SCA cumulative 20 years incidence, a lesion-specific stratification into four clusters-very-low (<1%), low (1%-4%), moderate (4%-12%) and high (>12%)-was built. Multivariable predictors were lesion-specific cluster, young age, male sex, unexplained syncope, ischaemic heart disease, non-life threatening ventricular arrhythmias, QRS duration and ventricular systolic dysfunction or hypertrophy. The model very accurately discriminated (C-index 0.91; 95% CI 0.88 to 0.94) and calibrated (p=0.3 for observed vs expected proportions) in the validation dataset. Compared with current guidelines approach, sensitivity increases 29% with less than 1% change in specificity. CONCLUSIONS: Predicting the risk of SCD/SCA in ACHD can be significantly improved using a baseline lesion-specific stratification and simple clinical variables.