Role of cardiac magnetic resonance in stratifying arrhythmogenic risk in mitral valve prolapse patients: a systematic review and meta-analysis.

OBJECTIVES: To perform a systematic review and meta-analysis of studies investigating the diagnostic value of cardiac magnetic resonance (CMR) features for arrhythmic risk stratification in mitral valve prolapse (MVP) patients. MATERIALS AND METHODS: EMBASE, PubMed/MEDLINE, and CENTRAL were searched for studies reporting MVP patients who underwent CMR with assessment of: left ventricular (LV) size and function, mitral regurgitation (MR), prolapse distance, mitral annular disjunction (MAD), curling, late gadolinium enhancement (LGE), and T1 mapping, and reported the association with arrhythmia. The primary endpoint was complex ventricular arrhythmias (co-VAs) as defined by any non-sustained ventricular tachycardia, sustained ventricular tachycardia, ventricular fibrillation, or aborted sudden cardiac death. Meta-analysis was performed when at least three studies investigated a CMR feature. PROSPERO registration number: CRD42023374185. RESULTS: The meta-analysis included 11 studies with 1278 patients. MR severity, leaflet length/thickness, curling, MAD distance, and mapping techniques were not meta-analyzed as reported in < 3 studies. LV end-diastolic volume index, LV ejection fraction, and prolapse distance showed small non-significant effect sizes. LGE showed a strong and significant association with co-VA with a LogORs of 2.12 (95% confidence interval (CI): [1.00, 3.23]), for MAD the log odds-ratio was 0.95 (95% CI: [0.30, 1.60]). The predictive accuracy of LGE was substantial, with a hierarchical summary ROC AUC of 0.83 (95% CI: [0.69, 0.91]) and sensitivity and specificity rates of 0.70 (95% CI: [0.41, 0.89]) and 0.80 (95% CI: [0.67, 0.89]), respectively. CONCLUSIONS: Our study highlights the role of LGE as the key CMR feature for arrhythmia risk stratification in MVP patients. MAD might complement arrhythmic risk stratification. CLINICAL RELEVANCE STATEMENT: LGE is a key factor for arrhythmogenic risk in MVP patients, with additional contribution from MAD. Combining MRI findings with clinical characteristics is critical for evaluating and accurately stratifying arrhythmogenic risk in MVP patients. KEY POINTS: MVP affects 2-3% of the population, with some facing increased risk for arrhythmia. LGE can assess arrhythmia risk, and MAD may further stratify patients. CMR is critical for MVP arrhythmia risk stratification, making it essential in a comprehensive evaluation.

Arrhythmic risk profile in mitral valve prolapse: A systematic review and metanalysis of 1715 patients.

INTRODUCTION: Mitral valve prolapse (MVP) is a common clinical condition in the general population. A subgroup of patients with MVP may experience ventricular arrhythmias and sudden cardiac death ("arrhythmic mitral valve prolapse" [AMVP]) but how to stratify arrhythmic risk is still unclear. Our meta-analysis aims to identify predictive factors for arrhythmic risk in patients with MVP. METHODS: We systematically searched Medline, Cochrane, Journals@Ovid, Scopus electronic databases for studies published up to December 28, 2022 and comparing AMVP and nonarrhythmic mitral valve prolapse (NAMVP) for what concerns history, electrocardiographic, echocardiographic and cardiac magnetic resonance features. The effect size was estimated using a random-effect model as odds ratio (OR) and mean difference (MD). RESULTS: A total of 10 studies enrolling 1715 patients were included. Late gadolinium enhancement (LGE) (OR: 16.67; p = .005), T-wave inversion (TWI) (OR: 2.63; p < .0001), bileaflet MVP (OR: 1.92; p < .0001) and mitral anulus disjunction (MAD) (OR: 2.60; p < .0001) were more represented among patients with AMVP than in NAMVP. Patients with AMVP were shown to have longer anterior mitral leaflet (AML) (MD: 2.63 mm; p < .0001), posterior mitral leaflet (MD: 2.96 mm; p < .0001), thicker AML (MD: 0.49 mm; p < .0001), longer MAD length (MD: 1.24 mm; p < .0001) and higher amount of LGE (MD: 1.41%; p < .0001) than NAMVP. AMVP showed increased mechanical dispersion (MD: 8.04 ms; 95% confidence interval: 5.13-10.96; p < .0001) compared with NAMVP. CONCLUSIONS: Our meta-analysis proved that LGE, TWI, bileaflet MVP, and MAD are predictive factors for arrhythmic risk in MVP patients.

Artificial Intelligence ECG Analysis in Patients with Short QT Syndrome to Predict Life-Threatening Arrhythmic Events.

Short QT syndrome (SQTS) is an inherited cardiac ion-channel disease related to an increased risk of sudden cardiac death (SCD) in young and otherwise healthy individuals. SCD is often the first clinical presentation in patients with SQTS. However, arrhythmia risk stratification is presently unsatisfactory in asymptomatic patients. In this context, artificial intelligence-based electrocardiogram (ECG) analysis has never been applied to refine risk stratification in patients with SQTS. The purpose of this study was to analyze ECGs from SQTS patients with the aid of different AI algorithms to evaluate their ability to discriminate between subjects with and without documented life-threatening arrhythmic events. The study group included 104 SQTS patients, 37 of whom had a documented major arrhythmic event at presentation and/or during follow-up. Thirteen ECG features were measured independently by three expert cardiologists; then, the dataset was randomly divided into three subsets (training, validation, and testing). Five shallow neural networks were trained, validated, and tested to predict subject-specific class (non-event/event) using different subsets of ECG features. Additionally, several deep learning and machine learning algorithms, such as Vision Transformer, Swin Transformer, MobileNetV3, EfficientNetV2, ConvNextTiny, Capsule Networks, and logistic regression were trained, validated, and tested directly on the scanned ECG images, without any manual feature extraction. Furthermore, a shallow neural network, a 1-D transformer classifier, and a 1-D CNN were trained, validated, and tested on ECG signals extracted from the aforementioned scanned images. Classification metrics were evaluated by means of sensitivity, specificity, positive and negative predictive values, accuracy, and area under the curve. Results prove that artificial intelligence can help clinicians in better stratifying risk of arrhythmia in patients with SQTS. In particular, shallow neural networks' processing features showed the best performance in identifying patients that will not suffer from a potentially lethal event. This could pave the way for refined ECG-based risk stratification in this group of patients, potentially helping in saving the lives of young and otherwise healthy individuals.

Asymptomatic Patients With Brugada ECG Pattern: Long-Term Prognosis From a Large Prospective Study.

BACKGROUND: Brugada syndrome poses significant challenges in terms of risk stratification and management, particularly for asymptomatic patients who comprise the majority of individuals exhibiting Brugada ECG pattern (BrECG). The aim of this study was to evaluate the long-term prognosis of a large cohort of asymptomatic patients with BrECG. METHODS: Asymptomatic patients with BrECG (1149) were consecutively collected from 2 Italian centers and followed-up at least annually for 2 to 22 years. For the 539 asymptomatic patients (men, 433 [80%]; mean age, 46±13 years) with spontaneous type 1 documented on baseline ECG (87%) or 12-lead 24-hour Holter monitoring (13%), an electrophysiologic study (EPS) was proposed; for the 610 patients with drug-induced-only type 1 (men, 420 [69%]; mean age, 44±14 years), multiple ECGs and 12-lead Holter were advised in order to detect the occurrence of a spontaneous type-1 BrECG. Arrhythmic events were defined as sudden death or documented ventricular fibrillation or tachycardia. RESULTS: Median follow-up was 6 (4-9) years. Seventeen (1.5%) arrhythmic events occurred in the overall asymptomatic population (corresponding to an event-rate of 0.2% per year), including 16 of 539 (0.4% per year) in patients with spontaneous type-1 BrECG and 1 of 610 in those with drug-induced type-1 BrECG (0.03% per year; P<0.001). EPS was performed in 339 (63%) patients with spontaneous type-1 BrECG. Patients with spontaneous type-1 BrECG and positive EPS had significantly higher event rates than patients with negative EPS (7 of 103 [0.7% per year] versus 4 of 236 [0.2% per year]; P=0.025). Among 200 patients who declined EPS, 5 events (0.4% per year) occurred. There was 1 device-related death. CONCLUSIONS: The entire population of asymptomatic patients with BrECG exhibits a relatively low event rate per year, which is important in view of the long life expectancy of these young patients. The presence of spontaneous type-1 BrECG associated with positive EPS identifies a subgroup at higher risk. Asymptomatic patients with drug-induced-only BrECG have a minimal arrhythmic risk, but ongoing follow-up with 12-lead Holter monitoring is recommended to detect the appearance of spontaneous type-1 BrECG pattern.

Risk of cardioembolic ischemic events and relation to atrial fibrillation/flutter in patients with arrhythmogenic cardiomyopathy during a long-term follow-up.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease characterized by fibro-fatty replacement of myocardium. Limited data is available concerning cardioembolic stroke. This study sought to determine the occurrence of cardioembolic ischemic events (CIEs) in ACM patients and to identify clinical and imaging predictors of CIEs. METHODS: Every consecutive ACM patient was enrolled. ECG, Holter monitoring or implantable cardiac devices were used to detect atrial arrhythmias (AAs). CIEs were defined according to TOAST classification. RESULTS: In our cohort of 111 patients, CIEs were observed in eleven (10%) over a 12.9-year median follow-up, with an incidence of 7.9 event/1000 patient-year (HR 4.12 compared to general population). Mean age at the event was 42 ± 9 years. Female sex (p = 0.03), T-wave inversion (p = 0.03), RVOT dilatation (p = 0.006) and lower LVEF (p = 0.006) were associated with CIEs. Among patients with AAs (23/111, 20.7%), 5 (21.7%) experienced CIEs. CHA2DS2-VASc did not prove useful to define patients at higher risk of CIEs (p = 0.098). 60% of stroke suffering patients had a pre-event score between 0 and 1 (if female). CONCLUSIONS: In ACM patients, CIEs are much more common than in general population and present a high burden at younger age. AAs relate to less than half of these events. In AAs patients, CHA2DS2-VASc is not useful to stratify those requiring oral anticoagulation. As a hypothesis-generating study, our research proposes the role of atrial myopathy, irrespective of AAs, as a pivotal factor in thrombogenesis risk, pointing out a definite unmet need in ACM therapeutic algorithm.

The Brugada syndrome: risk stratification.

Thirty years after its first description, the knowledge regarding Brugada syndrome has greatly increased. Spontaneous type 1 ECG pattern (BrECG) is a well-defined prognostic marker in asymptomatic patients and is associated with a double risk of arrhythmic events during follow-up as compared to drug-induced ECG pattern. Due to the extreme variability of the ECG pattern over time, the spontaneous type 1 BrECG must be carefully sought, not only through periodic ECGs but especially with repeated 12-lead 24-h Holter monitoring, with V1 and V2 electrodes placed also on the second and third intercostal space, in order to explore the right ventricular outflow tract. 12-lead 24-h Holter should also be performed in all the patients with a dubious BrECG pattern even before the drug challenge with sodium channel blockers, which carries a low but definite risk of complications. In addition to spontaneous type 1, other electrocardiographic markers of increased arrhythmic risk have been described, such as first-degree AV block, QRS fragmentation, S wave in lead I and II, and increased QRS duration. The electrophysiological study in asymptomatic patients with a spontaneous ECG Brugada pattern is still under jury and further studies need to clarify its precise role.

The Brugada syndrome: pharmacological therapy.

Brugada syndrome is an inherited channelopathy with an increased risk of sudden cardiac death (SCD) due to ventricular arrhythmias (VA) and an increased incidence of supraventricular arrhythmias, as compared with the general population. For the prevention of SCD, the guidelines recommend the implantable cardioverter-defibrillator (ICD); however, ICD does not prevent VA. In this article, we provide a brief review of the literature on the Brugada syndrome pharmacological therapy, mainly focusing on quinidine treatment. The efficacy of quinidine therapy in the prevention of VA in Brugada syndrome has been demonstrated by several small studies in patients with ICD and recurrent shocks or in asymptomatic patients with inducible ventricular fibrillation (VF) at electrophysiological study. Quinidine has also been tested for the prophylaxis of supraventricular arrhythmias, especially atrial fibrillation/flutter, and in paediatric patients. In these studies, quinidine proved highly effective in preventing re-induction of VF and spontaneous recurrences of both ventricular and supraventricular arrhythmias. Unfortunately, this therapy is burdened by a high incidence of side effects, which may lead to drug discontinuation.

Echocardiographic Parameters to Predict Malignant Events in Arrhythmic Mitral Valve Prolapse Population.

Bileaflet Mitral Valve Prolapse (bMVP) has been linked to major arrhythmic events and sudden cardiac death (SCD). Consistent predictors in this field are still lacking. Echocardiography is the best tool for the analysis of the prolapse and its impact on the ventricular mechanics. The aim of this study was to find new echocardiographic predictors of malignant events within an arrhythmic MVP population. We evaluated 22 patients with arrhythmic bMVP with a transthoracic echocardiogram focused on mitral valve anatomy and ventricular contraction. Six of them had major arrhythmic events that required ICD implantation (ICD-MVP group), while sixteen presented with a high arrhythmic burden without major events (A-MVP group). The best predictors of malignant events were the Anterior Mitral Leaflet (AML) greater length and greater Mechanical Dispersion (MD) of basal and mid-ventricular segments, while other significant predictors were the larger mitral valve annulus (MVA) indexed area, lower MVA anteroposterior diameter/AML length ratio, higher inferolateral basal segment S3 velocity.

Electrocardiographic findings in patients with arrhythmogenic cardiomyopathy and right bundle branch block ventricular tachycardia.

AIMS: Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data. METHODS AND RESULTS: From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV. CONCLUSIONS: In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants.

Prevalence and predictors of left atrial thrombosis in atrial fibrillation patients treated with non-vitamin K antagonist oral anticoagulants.

BACKGROUND: Few data are available regarding the prevalence of left atrium (LA) thrombi in atrial fibrillation (AF) patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). Methods: We evaluated the prevalence and predictors of LA/LA appendage (LAA) thrombi in non-valvular AF patients treated with NOACs referring to a single centre for a scheduled electrical cardioversion (ECV) or catheter ablation (CA). Transesophageal echocardiography (TEE) was performed within 12 h prior to the index procedure. RESULTS: A total of 352 consecutive patients with non-valvular AF treated with NOACs were included in this analysis (ECV group n = 176 and CA group n = 176) between 2013 and 2018. 85 patients (24.2%) were on dabigatran, 150 (42.7%) on rivaroxaban, 104 (29.6%) on apixaban and 13 (3.7%) on edoxaban. A LA/LAA thrombus was detected by TEE in 27 (7.7%) patients, 18 in the ECV group and nine in the ablation group; 18 (5.1%) patients presented dense LA/LAA spontaneous echo contrast (SEC). Predictors of LA/LAA thrombi were a CHA2DS2-VASc score > 3 (OR 4.54, 95% CI 1.50 - 13.70, p value = .007) and obesity (OR 6.01, 95% CI 1.95 - 18.50, p value = .001). CONCLUSIONS: Among real-world patients with non-valvular AF treated with NOACs, we found a high incidence of LA/LAA thrombi compared to previous reports. The main predictors of LA/LAA thrombosis were a CHA2DS2-VASc score > 3 and obesity.

Diagnostic and prognostic role of the electrocardiogram in patients with pericarditis.

OBJECTIVE: The ECG has been traditionally used to support the diagnosis of pericarditis. However, the pericardium is electrically silent and ECG changes may imply concurrent myocardial involvement rather than simple pericarditis. The aim of the present paper is to analyse the frequency, type and clinical implication of ECG changes in patients with pericarditis compared with those with myocarditis. METHODS: Consecutive patients with pericarditis and/or myocarditis were included in a prospective cohort study from January 2017 to December 2020. A clinical and echocardiographic follow-up was performed at 1, 3, 6 months and then every 6 months. Cardiac magnetic resonance was used to diagnose concurrent myocarditis. RESULTS: 166 patients (median age 47 years, 95% CI 44 to 51) with 66 men (39.8%) were included: 110 cases with pericarditis (mean age 47.7 years, 29.1% male) and 56 cases with myocarditis (mean age 44.8, 60.7% male). ECG changes were reported in 61 of 166 (36.7%) patients: 27 of 110 (24.5%) among those with pericarditis and 34 of 56 (60.7%) among those with myocarditis (p<0.0001). In multivariate logistic regression analysis, ECG changes were associated with troponin elevation (risk ratio 1.97; 95% CI 1.13 to 3.43), suggesting myocardial involvement. ECG changes were not associated with increased risk of adverse events. CONCLUSIONS: ECG changes, mainly widespread ST-segment elevation, can be recorded in about one-quarter of patients with pericarditis, and were not associated with a worse prognosis. These changes may reflect concurrent myocarditis that should be ruled out.

Prognostic role of left atrial enlargement in patients with implantable cardioverter defibrillators for primary prevention.

PURPOSE: Left atrial volume index (LAVI) is a predictor of heart failure and adverse events, irrespective of left ventricular systolic function. The role of LAVI in the prediction of appropriate implantable cardioverter-defibrillator (ICD) therapies is currently unclear and was the focus of this study. METHODS: Consecutive heart failure patients with ischaemic (ICM) or idiopathic (DCM) aetiology receiving ICD for primary prevention were included. The primary endpoint was the occurrence of appropriate ICD therapies (ATs): shocks or antitachycardia pacing (ATP). Inappropriate ICD shocks were also assessed as secondary endpoint. RESULTS: Among 198 included patients, severe left atrial dilatation (SLAE = LAVI ≥ 60 ml/m2) was present in 54 (27%). SLAE patients had a higher prevalence of NYHA class ≥ III, severe mitral regurgitation and atrial fibrillation history. During a median follow-up of 45 months (IQR 25-68), ATs occurred more frequently in SLAE group (33% vs. 15%, p = .007) as well as appropriate shocks (24% vs. 10%, p = .014). At multivariate analysis SLAE was an independent predictor of ATs (OR 3.19, 95% CI 1.38-7.38, p = .007). Inappropriate shocks were associated with AF during implantation (p = .03), but not with SLAE (p = .009). CONCLUSION: In DCM or ICM patients candidate to receive an ICD for primary prevention, a severely enlarged left atrium is a predictive factor for ATs (shocks or ATP). The risk of inappropriate shocks was increased in patients with atrial fibrillation, rather than SLAE.

The prevalence of left and right bundle branch block morphology ventricular tachycardia amongst patients with arrhythmogenic cardiomyopathy and sustained ventricular tachycardia: insights from the European Survey on Arrhythmogenic Cardiomyopathy.

AIMS: In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics. METHODS AND RESULTS: Twenty-six centres from 11 European countries provided information on 954 ACM patients who had ≥1 episode of sustained VT spontaneously documented during patients' clinical course. Arrhythmogenic cardiomyopathy was defined according to the 2010 Task Force Criteria, and VT morphology according to the QRS pattern in V1. Overall, 882 (92.5%) patients displayed LBBB-VT alone and 72 (7.5%) RBBB-VT [alone in 42 (4.4%) or in combination with LBBB-VT in 30 (3.1%)]. Male sex prevalence was 79.3%, 88.1%, and 56.7% in the LBBB-VT, RBBB-VT, and LBBB + RBBB-VT groups, respectively (P = 0.007). First RBBB-VT occurred 5 years after the first LBBB-VT (46.5 ± 14.4 vs 41.1 ± 15.8 years, P = 0.011). An implanted cardioverter-defibrillator was more frequently implanted in the RBBB-VT (92.9%) and the LBBB + RBBB-VT groups (90%) than in the LBBB-VT group (68.1%) (P < 0.001). Mutations in PKP2 predominated in the LBBB-VT (65.2%) and the LBBB + RBBB-VT (41.7%) groups while DSP mutations predominated in the RBBB-VT group (45.5%). By multivariable analysis, female sex was associated with LBBB + RBBB-VT (P = 0.011) while DSP mutations were associated with RBBB-VT (P < 0.001). After a median follow-up of 103 (51-185) months, death occurred in 106 (11.1%) patients with no intergroup difference (P = 0.176). CONCLUSION: RBBB-VT accounts for a significant proportion of sustained VTs in ACM. Sex and type of pathogenic mutations were associated with VT type, female sex with LBBB + RBBB-VT, and DSP mutation with RBBB-VT.

Long-term efficacy and impact on quality of life of atrial fibrillation catheter ablation in competitive athletes.

BACKGROUND: Limited data are available on the efficacy of catheter ablation (CA) for sport-associated atrial fibrillation (AF), in particular at long term follow-up. Moreover, the impact of AF CA on Quality of Life (QoL) in this population remains unknown. We aimed to determine AF CA efficacy in athletes, to assess the impact on athletes' QoL (with SF36 score) and on training capabilities in a long-term follow-up (FU). METHODS: A total of 1215 AF patients' candidates to CA between January 2007 and December 2012, were retrospectively screened. Athletes were defined as patients performing ≥5 h/week of vigorous sports, achieving a total of ≥1500 h lifetime sport activity, for at least one year before AF first symptomatic episode. RESULTS: Out of 1215 AF patients, 133 were considered competitive athletes and underwent CA. Overall, 43% of our cohort showed typical or atypical atrial flutter, which required a more extensive ablation procedure. Before AF, athletes used to practice for a mean of 8.5±2.7 h/week, while after the first AF episode the mean practice duration decreased to 2.8±2.5 h/week. At 10-year follow-up, 83% of athletes did not present any recurrent event, and training capabilities increased up to 5.6±3.6 h/week after the procedure. Moreover, intense physical activity before AF CA was related to long-term AF recurrence rates (P=0.05). QoL scores significantly improved in each single domain (P<0.05). CONCLUSIONS: AF CA represents an effective procedure to maintain sinus rhythm in athletes, with a significant improvement in QoL.

Genotype-Phenotype Correlation of SCN5A Genotype in Patients With Brugada Syndrome and Arrhythmic Events: Insights From the SABRUS in 392 Probands.

BACKGROUND: Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, SCN5A. However, genetic studies of patients with BrS with arrhythmic events have been limited. We sought to compare various clinical, ECG, and electrophysiological parameters according to SCN5A genotype in a large cohort of BrS probands with first arrhythmic event. METHODS: Survey on Arrhythmic Events in Brugada Syndrome is a survey of 10 Western and 4 Asian countries, gathering 678 patients with BrS with first arrhythmic event. Only probands were included, and SCN5A genotype adjudicated. Patients without appropriate genetic data were excluded. Associations of genotype with clinical features were analyzed. RESULTS: The study group comprised 392 probands: 92 (23.5%) SCN5A+(44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) SCN5A-.SCN5A missense variants and the patients hosting them were similar regardless of adjudication. A higher proportion of patients with P/LP were pediatric (<16 years) compared with SCN5A- (11.4% versus 3%, P=0.023). The proportion of females was higher among patients with P/LP compared with SCN5A- (18.2% versus 6.3%, P=0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with SCN5A- (41.9% versus 16.8%, P<0.001). A higher proportion of patients with P/LP were White compared with SCN5A- (87.5% versus 47%, P<0.001). Ethnicity (odds ratio, 5.41 [2.8-11.19], P<0.001) and family history of sudden cardiac death (odds ratio, 2.73 [1.28-5.82], P=0.009) were independent variables associated with P/LP genotype following logistic regression. CONCLUSIONS: The genetic basis of BrS has a complex relationship with gender, ethnicity, and age. Probands hosting a P/LP variant tended to experience their first arrhythmic event at a younger age and to have events triggered by fever compared with patients with SCN5A-. In addition, they were more likely to be White and to have family history of sudden cardiac death. Among females, a P/LP variant suggests an increased risk of being symptomatic. This association should be further studied on an ethnically specific basis in large prospectively collected international cohorts.

The Torino Pericarditis Score: a new-risk stratification tool to predict complicated pericarditis.

Current guidelines on the management of pericardial diseases suggest to identify high-risk features associated with an increased risk of non-idiopathic aetiology and complications. The aim of this study is to evaluate a "pericarditis score" to assess potential complicated pericarditis in order to facilitate initial clinical triage. Consecutive patients with pericarditis were included in a prospective cohort study from January 2017 to December 2018. Complicated pericarditis was defined as pericarditis with a non-idiopathic aetiology, and/or complications, and/or requiring hospitalization. A clinical and echocardiographic follow-up were performed at 1, 3, 6 months and then every 6 months. The study population was randomized in derivation and validation cohorts. In the derivation cohort, female gender (HR 2.57, p = 0.016), fever > 38 °C (HR 2.86, p = 0.005), previous lack of colchicine use (HR 3.16, p = 0.006), previous use of corticosteroids (HR 3.01, p = 0.009), and echocardiographic signs of constriction (HR 2.26, p = 0.018) were selected by a stepwise procedure in a Cox regression model and constituted the score showing a C-statistics of 0.81. In the validation group, the score was significantly associated with the risk of complicated pericarditis (HR 1.438 per 10-points increase, 95% CI 1.208-1.711, p < 0.001) and showed an increase in event rate with increasing score (low risk ≤ 20 points: complicated pericarditis in 4/19 patients, incidence 21%, p = 0.003, high risk > 40 points: complicated pericarditis in 18/24 patients, incidence 75%, p = 0.006). In this study, we developed and tested a simple score to efficiently identify at presentation patients at high risk of developing complicated pericarditis.