[New frontiers in pacing: from myocardial pacing to conduction system pacing]. / Nuove frontiere dell'elettrostimolazione: dal pacing del miocardio comune al pacing del sistema di conduzione.

For many years, cardiac pacing has been based on the stimulation of right ventricular common myocardium to correct diseases of the conduction system. The birth and the development of cardiac resynchronization have led to growing interest in the correction and prevention of pacing-induced dyssynchrony. Many observational studies and some randomized clinical trials have shown that conduction system pacing (CSP) can not only prevent pacing-induced dyssynchrony but can also correct proximal conduction system blocks, with reduction of QRS duration and with equal or greater effectiveness than biventricular pacing. Based on these results, many Italian electrophysiologists have changed the stimulation target from the right ventricular common myocardium to CSP. The two techniques with greater clinical impact are the His bundle stimulation and the left bundle branch pacing. The latter, in particular, because of its easier implantation technique and better electric parameters, is spreading like wildfire and is representing a real revolution in the cardiac pacing field. However, despite the growing amount of data, until now, the European Society of Cardiology guidelines give a very limited role to CSP.

Real-world data of patients affected by advanced heart failure treated with implantable cardioverter defibrillator and left ventricular assist device: Results of a multicenter observational study.

BACKGROUND: Left ventricular assist device (L-VAD) implantation is increasingly used in patients with heart failure (HF) and most patients also have an implantable cardioverter defibrillator (ICD). Limited data are available on the incidence of ICD therapies and complications in this special setting. The aim of this study was to analyze the real-world incidence and predictors of ICD therapies, complications and interactions between ICD and L-VAD. METHODS: We conducted a multicenter retrospective observational study in patients with advanced HF implanted with ICD and a continuous-flow L-VAD, followed-up in five advanced HF centers in Northern Italy. RESULTS: A total of 234 patients (89.7% male, median age 59, 48.3% with ischemic etiology) were enrolled. After a median follow-up of 21 months, 66 patients (28.2%) experienced an appropriate ICD therapy, 22 patients (9.4%) an inappropriate ICD therapy, and 17 patients (7.3%) suffered from an interaction between ICD and L-VAD. The composite outcome of all ICD-related complications was reported in 41 patients (17.5%), and 121 (51.7%) experienced an L-VAD-related complication. At multivariable analysis, an active ventricular tachycardia (VT) zone and a prior ICD generator replacement were independent predictors of ICD therapies and of total ICD-related complications, respectively. CONCLUSIONS: Real-world patients with both L-VAD and ICD experience a high rate of ICD therapies and complications. Our findings suggest the importance of tailoring device programming in order to minimize the incidence of unnecessary ICD therapies, thus sparing the need for ICD generator replacement, a procedure associated to a high risk of complications.

[Electrical storm management in the cardiac care unit]. / Gestione della tempesta aritmica in terapia intensiva cardiologica.

Electrical storm (ES) is characterized by at least three separate episodes of ventricular arrhythmia (VA) over 24 h that require treatment or an incessant VA lasting >12 h. The incidence is higher in patients with implantable cardioverter-defibrillators (ICDs) in secondary prevention and the main manifestation is monomorphic VA. ES onset represents a major event in the history of patients with cardiomyopathies that significantly worsens prognosis. The management of ES is complex and requires a multidisciplinary approach including a comprehensive clinical assessment, resuscitation and sedation management skills, ICD reprogramming, ablation, and neuromodulation procedures. ES early recognition and prompt treatment initiation increase the chances of therapeutic success. Each one of these aspects will be properly discussed in the present decalogue. Notably, ES management remains a challenge, with only limited available evidence from small retrospective series and a substantial lack/limited number of randomized or prospective trials. The spectrum of available antiarrhythmic drugs is limited, as well as their efficacy. The future hope is that larger prospective studies will be able to answer important questions, concerning the most effective pharmacologic strategies, the timing for the invasive treatment, the indications for acute neuromodulation strategies and for the circulatory support tools.

The impact of mitral valve surgery on ventricular arrhythmias in patients with Barlow's disease: preliminary results of a prospective study.

OBJECTIVES: Aim of this study was to evaluate arrhythmic burden of patients with Barlow's disease and significant mitral regurgitation (MR) and assess the impact of mitral repair on ventricular arrhythmias (VA) in this group of subjects. METHODS: We prospectively included 88 consecutive patients with Barlow's disease referred to our Institution from February 2021 to May 2022. All enrolled patients underwent 24-h Holter monitoring before surgery. Sixty-three of them completed 3 months echocardiographic and Holter follow-up. Significant arrhythmic burden was defined as ≥1% premature ventricular beats/24 h or at least one episode of non-sustained ventricular tachycardia (VT), VT or ventricular fibrillation. RESULTS: At baseline, 29 patients (33%) were arrhythmogenic (AR), while 59 (67%) were not [non-arrhythmogenic (NAR)]. AR subjects tended to be more often females with history of palpitations. Sixty-three patients completed 3-months follow-up. Twenty of them (31.7%) were AR at baseline and 43 (68.3%) were not. Among AR patients, 9 (45%) remained AR after mitral surgery, while 11 (55%) became NAR. Considering NAR subjects at baseline, after mitral valve repair 8 (18.6%) evolved into AR, while 35 (81.4%) remained NAR. A higher prevalence of pre-operative MAD was found among patients experiencing VA reduction if compared with patients who remained arrhythmogenic (63.6% vs 11.1%, P = 0.028). CONCLUSIONS: In our experience, one-third of Barlow's patients referred for mitral surgery showed a significant arrhythmic burden. Almost half of the subjects arrhythmogenic at baseline were free from significant VA after mitral repair. However, a minority (18.6%) of subjects without arrhythmic burden at baseline experienced significant VA at follow-up.

Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study.

BACKGROUND: Different genes have been associated with idiopathic ventricular fibrillation (IVF); however, there are no studies correlating genotype with phenotype. OBJECTIVES: The aim of this study was to define the genetic background of probands with IVF using large gene panel analysis and to correlate genetics with long-term clinical outcomes. METHODS: All consecutive probands with a diagnosis of IVF were included in a multicenter retrospective study. All patients had: 1) IVF diagnosis throughout the follow-up; and 2) genetic analysis with a broad gene panel. All genetic variants were classified as pathogenic/likely pathogenic (P+), variants of unknown significance (VUS) or no variants (NO-V), following current guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The primary endpoint was occurrence of ventricular arrhythmias (VA). RESULTS: Forty-five consecutive patients were included. A variant was found in 12 patients, 3 P+ and 9 VUS carriers. After a mean follow-up time of 105.0 months, there were no deaths and 16 patients (35.6%) experienced a VA. NO-V patients had higher VA free survival during the follow-up, compared with both VUS (72.7% vs 55.6%, log-rank P < 0.001) and P+ (72.7% vs 0%, log-rank P = 0.013). At Cox analysis, P+ or VUS carrier status was a predictor of VA occurrence. CONCLUSIONS: In probands with IVF, undergoing genetic analysis with a broad panel, the diagnostic yield for P+ is 6.7%. P+ or VUS carrier status is a predictor of VA occurrence.

Genetic testing in children with Brugada syndrome: results from a large prospective registry.

AIMS: A pathogenic/likely pathogenic (P/LP) variant in SCN5A is found in 20-25% of patients with Brugada syndrome (BrS). However, the diagnostic yield and prognosis of gene panel testing in paediatric BrS is unclear. The aim of this study is to define the diagnostic yield and outcomes of SCN5A gene testing with ACMG variant classification in paediatric BrS patients compared with adults. METHODS AND RESULTS: All consecutive patients diagnosed with BrS, between 1992 and 2022, were prospectively enrolled in the UZ Brussel BrS registry. Inclusion criteria were: (i) BrS diagnosis; (ii) genetic analysis performed with a large gene panel; and (iii) classification of gene variants following ACMG guidelines. Paediatric patients were defined as ≤16 years of age. The primary endpoint was ventricular arrhythmias (VAs). A total of 500 BrS patients were included, with 63 paediatric patients and 437 adult patients. Among children with BrS, 29 patients (46%) had a P/LP variant (P+) in SCN5A and no variants were found in 34 (54%) patients (P-). After a mean follow-up of 125.9 months, 8 children (12.7%) experienced a VA, treated with implanted cardioverter defibrillator shock. At survival analysis, P- paediatric patients had higher VA-free survival during the follow-up, compared with P+ paediatric patients. P+ status was an independent predictor of VA. There was no difference in VA-free survival between paediatric and adult BrS patients for both P- and P+. CONCLUSION: In a large BrS cohort, the diagnostic yield for P/LP variants in the paediatric population is 46%. P+ children with BrS have a worse arrhythmic prognosis.

[2020 Catheter Ablation Registry of the Italian Association of Arrhythmology and Cardiac Pacing]. / Registro Italiano Ablazioni 2020. Associazione Italiana di Aritmologia e Cardiostimolazione.

BACKGROUND: This report describes the findings of the 2020 Italian Catheter Ablation Registry of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC). METHODS: Data collection was retrospective. A standardized questionnaire was completed by each of the participating centers. RESULTS: A total of 10 378 ablation procedures were performed by 66 institutions. Most centers (70%) have an electrophysiology laboratory, and 23% a hybrid cardiac surgery laboratory. All centers have a 3D mapping system. The median number of electrophysiologists and nurses involved in the electrophysiology laboratory was 3.5 and 3, respectively. An electrophysiology technician was involved in 35% of all centers. In 88.2% of cases, catheter ablation was performed for supraventricular arrhythmias; the most frequently treated arrhythmia was atrial fibrillation (39.4%), followed by atrioventricular nodal reentrant tachycardia (18.6%), and common atrial flutter (10.6%). In 72.9% of patients, catheter ablation was performed using a 3D mapping system, with a "near-zero" fluoroscopic approach in 37.7% of all patients. CONCLUSIONS: The 2020 Italian Catheter Ablation Registry confirmed that the electrophysiology activity was markedly affected by the COVID-19 pandemic; atrial fibrillation is the most frequently treated arrhythmia with an increasing number of procedures performed with a 3D mapping system and a "near-zero" approach.

Role of comorbidities on the mortality in patients with SARS-CoV-2 infection: an Italian cohort study.

BACKGROUND: Cardiovascular comorbidities are a common cause of death in COVID-19 and the aim of this study is to evaluate the effect of comorbidities on mortality in COVID-19 patients. METHODS: In this retrospective observational study we enrolled 1049 patients hospitalized with confirmed SARS-CoV-2 infection in a single Italian Center from 21 February to 20 March 2020 Evaluated risk factors (RFs) were: advanced age, gender, hypertension, diabetes, atrial fibrillation, hyperlipidemia, chronic kidney disease, thyroid disease, chronic obstructive pulmonary disease, malignancy, stroke, cardiovascular disease, and peripheral vascular disease. Endpoint of the study was death from any cause. A multivariate logistic regression model was built using covariates that showed as statistically significant at univariate regression analysis. RESULTS: Median age at presentation was 71.1 years (IQR: 59.1-80.5); 244 (72.2%) were males. Primary outcome occurred in 338 patients (32.2%). In decedents, median survival from Hospitalization was 6 (IQR: 3-10) days. 264 decedents had 1 RF, 120 had 2 RFs and 39 had ≥3 RFs. At multivariate logistic regression model, variables associated with primary outcome were: age class (64-69 years) (OR 3.03, CI: 1.75-5.31, P<0.001), age class (70-88 years) (OR 10.08, CI: 6.67-15.72, P<0.001), age class (≥88 years) (OR 23.99, CI: 13.21-44.82, P<0.001), male gender (OR 1.88, CI: 1.36-2.62, P<0.001), diabetes (OR 1.56, CI: 1.07-2.26, P=0.02), stroke (OR 3.41, CI: 1.33-9.91, P=0.015). CONCLUSIONS: Age, male gender, presence of diabetes and stroke appeared as independent predictors of mortality in COVID-19 patients. A table for risk of 30 days-mortality in SARS-CoV-2 infection was built, based on odds ratios derived from multivariate regression analysis.

Long-Term Follow-Up of Catheter Ablation for Premature Ventricular Complexes in the Modern Era: The Importance of Localization and Substrate.

Background: Large-scale studies evaluating long-term recurrence rates in both idiopathic and non-idiopathic PVC catheter ablation (CA) patients have not been reported. Objective: To evaluate the efficacy and safety of idiopathic and non-idiopathic PVC CA, investigating the predictors of acute and long-term efficacy. Methods: This retrospective multicentric study included 439 patients who underwent PVC CA at three institutions from April-2015 to December-2021. Clinical success at 6 months' follow-up, defined as a reduction of at least 80% of the pre-procedural PVC burden, was deemed the primary outcome. The secondary aims of the study were: clinical success at the last available follow-up, predictors of arrhythmic recurrences at long-term follow-up, and safety outcomes. Results: The median age was 51 years, with 24.9% patients being affected suffering from structural heart disease. The median pre-procedural PVC burden was 20.1%. PVCs originating from the RVOT were the most common index PVC observed (29.1%), followed by coronary cusp (CC) and non-outflow tract (OT) LV PVCs (23.1% and 19.0%). The primary outcome at 6 months was reached in 85.1% cases, with a significant reduction in the 24 h% PVC burden (−91.4% [−83.4; −96.7], p < 0.001); long-term efficacy was observed in 82.1% of cases at almost 3-year follow-up. The presence of underlying structural heart disease and non-OT LV region origin (aHR 1.77 [1.07−2.93], p = 0.027 and aHR = 1.96 [1.22−3.14], p = 0.005) was independently associated with recurrences. Conclusion: CA of both idiopathic and non-idiopathic PVCs showed a very good acute and long-term procedural success rate, with an overall low complication. Predictors of arrhythmic recurrence at follow-up were underlying structural heart disease and non-OT LV origin.

Patients with Cardiac Implantable Electronic Device Undergoing Radiation Therapy: Insights from a Ten-Year Tertiary Center Experience.

BACKGROUND: The number of patients with cardiac implantable electronic devices (CIEDs) receiving radiotherapy (RT) is increasing. The management of CIED-carriers undergoing RT is challenging and requires a collaborative multidisciplinary approach. AIM: The aim of the study is to report the real-world, ten-year experience of a tertiary multidisciplinary teaching hospital. METHODS: We conducted an observational, real-world, retrospective, single-center study, enrolling all CIED-carriers who underwent RT at the San Raffaele University Hospital, between June 2010 and December 2021. All devices were MRI-conditional. The devices were programmed to an asynchronous pacing mode for patients who had an intrinsic heart rate of less than 40 beats per minute. An inhibited pacing mode was used for all other patients. All tachyarrhythmia device functions were temporarily disabled. After each RT session, the CIED were reprogrammed to the original settings. Outcomes included adverse events and changes in the variables that indicate lead and device functions. RESULTS: Between June 2010 and December 2021, 107 patients were enrolled, among which 63 (58.9%) were pacemaker carriers and 44 (41.1%) were ICD carriers. Patients were subjected to a mean of 16.4 (±10.7) RT sessions. The most represented tumors in our cohort were prostate cancer (12; 11%), breast cancer (10; 9%) and lung cancer (28; 26%). No statistically significant changes in device parameters were recorded before and after radiotherapy. Generator failures, power-on resets, changes in pacing threshold or sensing requiring system revision or programming changes, battery depletions, pacing inhibitions and inappropriate therapies did not occur in our cohort of patients during a ten-year time span period. Atrial arrhythmias were recorded during RT session in 14 patients (13.1%) and ventricular arrhythmias were observed at device interrogation in 10 patients (9.9%). CONCLUSIONS: Changes in device parameters and arrhythmia occurrence were infrequent, and none resulted in a clinically significant adverse event.

Feasibility of leadless left ventricular septal pacing with the WiSE-CRT system to target the left bundle branch area: A porcine model and multicenter patient experience.

BACKGROUND: The WiSE-CRT system delivers leadless endocardial left ventricular (LV) pacing to achieve cardiac resynchronization therapy. The electrode is conventionally placed on the lateral wall, but implanting on the LV septum may have advantages, including capture of the left bundle branch, and improved battery longevity owing to reduced distance from the transmitter. OBJECTIVE: The purpose of this study was to assess the feasibility of leadless LV septal pacing via the WiSE-CRT system. METHODS: Two pigs underwent electrode implantation on the LV septum with subsequent anatomical and histological examination. Eight patients underwent implantation of the WiSE-CRT system with deployment of the electrode on the LV septum via an interatrial transseptal approach. RESULTS: Deployment of the electrode on the LV septum was successful in both animals. Histological examination demonstrated electrode tines in close proximity to Purkinje tissue. WiSE-CRT implantation with an LV septal electrode was successful in all patients. Biventricular capture was confirmed, with a significant reduction in QRS duration (187.1 ± 33.8 ms vs 149.5 ± 15.7 ms; P = .009). Temporary LV pacing achieved further QRS reduction (139.8 ± 12.4 ms), and in 4 patients the peak LV activation time in lead V5/V6 was <90 ms, suggesting left bundle branch capture. At early follow-up, the median LV pacing percentage was 98.5% and 5 patients (62.5%) improved symptomatically. The transmitter-to-electrode distance was lower than the distance to the lateral wall during acoustic window screening (8.8 ± 1.6 cm vs 11.9 ± 1.5 cm; P = .002). CONCLUSION: Leadless LV septal pacing with the WiSE-CRT system to target the left bundle branch appears feasible. Further study is required to assess the efficacy and safety of this technique.

Significance of abnormal and late ventricular signals in ventricular tachycardia ablation of ischemic and nonischemic cardiomyopathies.

BACKGROUND: Abnormal ventricular signals (AVS) are the cornerstone of substrate-based ventricular tachycardia (VT) ablation in sinus rhythm. Signal characterization of AVS in ischemic and nonischemic cardiomyopathies has never been performed. OBJECTIVE: The purpose of this study was to describe ventricular signal abnormalities in 3 different pathologies and examine their association with the diastolic component of VT circuits. METHODS: A total of 45 patients (15 ischemic cardiomyopathy [ICM], 15 arrhythmogenic cardiomyopathy [ACM], 15 dilated cardiomyopathy [DCM]) who had undergone VT ablation with >50% of the diastolic pathway of the VT circuit recorded were studied. AVS were classified into late potentials (LPs) and continuous fractionated ventricular signals (CFVS), and their characteristics and correlation with the diastolic pathway of VT circuits were analyzed. RESULTS: Seventy-five VT circuits were analyzed. Bipolar scars were greatest in ICM endocardially (53 cm2 ICM vs 36 cm2 ACM vs 25 cm2 DCM; P = .010) and in ACM epicardially (98 cm2 ACM vs 25 cm2 ICM vs 24 cm2 DCM; P = .005). Location of the VT diastolic interval coincided with AVS location in 54% of VTs in ICM, 89% in ACM, and 72% in DCM (P = .036). There was a trend toward a greater association of diastolic intervals coinciding with LPs than with CFVS (78% vs 57%; P = .052) (69% diastolic intervals in ICM coincided with LPs, 33% with CFVS; P = .063). All patients (100%) with CFVS in ACM had VT diastolic components arising from CFVS (33% ICM, 64% DCM; P = .049). Positive predictive value for LPs vs CFVS was 77.8% vs 56.7%, and sensitivity was 67.3% vs 32.7%, respectively. CONCLUSION: The nature of abnormal signals in different cardiomyopathies reflects underlying pathology. LPs rather than CFVS seem to be more linked to diastolic components of VT circuits, especially in ICM. LPs have greater sensitivity and specificity for VT; however, CFVS may be of more relevance in ACM.

Incidence and Predictors of Cardiac Arrhythmias in Patients With COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is a systemic disease caused by severe acute respiratory syndrome coronavirus 2. Arrhythmias are frequently associated with COVID-19 and could be the result of inflammation or hypoxia. This study aimed to define the incidence of arrhythmias in patients with COVID-19 and to correlate arrhythmias with pulmonary damage assessed by computed tomography (CT). Methods: All consecutive patients with a COVID-19 diagnosis hospitalized at Universitair Ziekenhuis Brussel, Belgium, between March 2020 and May 2020, were screened. All included patients underwent a thorax CT scan and a CT severity score, a semiquantitative scoring system of pulmonary damage, was calculated. The primary endpoint was the arrhythmia occurrence during follow-up. Results: In this study, 100 patients were prospectively included. At a mean follow-up of 19.6 months, 25 patients with COVID-19 (25%) experienced 26 arrhythmic episodes, including atrial fibrillation in 17 patients, inappropriate sinus tachycardia in 7 patients, atrial flutter in 1 patient, and third-degree atrioventricular block in 1 patient. No ventricular arrhythmias were documented. Patients with COVID-19 with arrhythmias showed more often need for oxygen, higher oxygen maximum flow, longer QTc at admission, and worse damage at CT severity score. In univariate logistic regression analysis, significant predictors of the primary endpoint were: the need for oxygen therapy (odds ratio [OR] 4.59, 95% CI 1.44-14.67, p = 0.01) and CT severity score of pulmonary damage (OR per 1 point increase 1.25, 95% CI 1.11-1.4, p < 0.001). Conclusions: In a consecutive cohort of patients with COVID-19 the incidence of cardiac arrhythmias was 25%. The need for oxygen therapy and CT severity score were predictors of arrhythmia occurrence during follow-up.

Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator? Results From the Multicenter Randomized PARTITA Trial.

BACKGROUND: Optimal timing for catheter ablation of ventricular tachycardia is an important unresolved issue. There are no randomized trials evaluating the benefit of ablation after the first implantable cardioverter defibrillator (ICD) shock. METHODS: We conducted a 2-phase, prospective, multicenter, randomized clinical trial. Patients with ischemic or nonischemic dilated cardiomyopathy and primary or secondary prevention indication for ICD were enrolled in an initial observational phase until first appropriate shock (phase A). After reconsenting, patients were randomly assigned 1:1 in phase B to immediate ablation (within 2 months from shock delivery) or continuation of standard therapy. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure. Amiodarone intake was not allowed except for documented atrial tachyarrhythmias. On July 23, 2021, phase B of the trial was interrupted as a result of the first interim analysis on the basis of the Bayesian adaptive design. RESULTS: Of the 517 patients enrolled in phase A, 154 (30%) had ventricular tachycardia, 56 (11%) received an appropriate shock over a median follow-up of 2.4 years (interquartile range, 1.4-4.4), and 47 of 56 (84%) agreed to participate in phase B. After 24.2 (8.5-24.4) months, the primary end point occurred in 1 of 23 (4%) patients in the ablation group and 10 of 24 (42%) patients in the control group (hazard ratio, 0.11 [95% CI, 0.01-0.85]; P=0.034). The results met the prespecified termination criterion of >99% Bayesian posterior probability of superiority of treatment over standard therapy. No deaths were observed in the ablation group versus 8 deaths (33%) in the control group (P=0.004); there was 1 worsening heart failure hospitalization in the ablation group (4%) versus 4 in the control group (17%; P=0.159). ICD shocks were less frequent in the ablation group (9%) than in the control group (42%; P=0.039). CONCLUSIONS: Ventricular tachycardia ablation after first appropriate shock was associated with a reduced risk of the combined death or worsening heart failure hospitalization end point, lower mortality, and fewer ICD shocks. These findings provide support for considering ventricular tachycardia ablation after the first ICD shock. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01547208.

Bi-atrial characterization of the electrical substrate in patients with atrial fibrillation.

BACKGROUND: Little is known regarding the characterization of electrical substrate in both atria in patients with atrial fibrillation (AF). METHODS: Eight consecutive patients undergoing AF ablation (five paroxysmal, three persistent) underwent electrical substrate characterization during sinus rhythm. Mapping of the left (LA) and right atrium (RA) was performed with the use of the HD Grid catheter (Abbott). Bipolar voltage maps were analyzed to search for low voltage areas (LVA), the following electrophysiological phenomena were assessed: (1) slow conduction corridors, and (2) lines of block. EGMs were characterized to search for fractionation. Electrical characteristics were compared between atria and between paroxysmal versus persistent AF patients. RESULTS: In the RA, LVAs were present in 60% of patients with paroxysmal AF and 100% of patients with persistent AF. In the LA, LVAs were present in 40% of patients with paroxysmal AF and 66% of patients with persistent AF. The areas of LVA in the RA and LA were 4.8±7.3 cm2 and 7.8±13.6 cm2 in patients with paroxysmal AF versus 11.7±3.0 cm2 and 2.1±1.8 cm2 in patients with persistent AF. In the RA, slow conduction corridors were present in 40.0% (paroxysmal AF) versus 66.7% (persistent AF) whereas in the LA, slow conduction corridors occurred in 20.0% versus 33.3% respectively (p = ns). EGM analysis showed more fractionation in persistent AF patients than paroxysmal (RA: persistent AF 10.8 vs. paroxysmal AF 4.7%, p = .036, LA: 10.3 vs. 4.1%, p = .108). CONCLUSION: Bi-atrial involvement is present in patients with paroxysmal and persistent AF. This is expressed by low voltage areas and slow conduction corridors whose extension progresses as the arrhythmia becomes persistent. This electrophysiological substrate demonstrates the important interplay with the pulmonary vein triggers to constitute the substrate for persistent arrhythmia.

Clinical characteristics and outcomes of patients with ventricular arrhythmias after continuous-flow left ventricular assist device implant.

BACKGROUND: Ventricular arrhythmias (VAs) are observed in 25%-50% of continuous-flow left ventricular assist device (CF-LVAD) recipients, but their role on mortality is debated. METHODS: Sixty-nine consecutive patients with a CF-LVAD were retrospectively analyzed. Study endpoints were death and occurrence of first episode of VAs post CF-LVAD implantation. Early VAs were defined as VAs in the first month after CF-LVAD implantation. RESULTS: During a median follow-up of 29.0 months, 19 patients (27.5%) died and 18 patients (26.1%) experienced VAs. Three patients experienced early VAs, and one of them died. Patients with cardiac resynchronization therapy (CRT-D) showed a trend toward more VAs (p = 0.076), compared to patients without CRT-D; no significant difference in mortality was found between patients with and without CRT-D (p = 0.63). Patients with biventricular (BiV) pacing ≥98% experienced more frequently VAs (p = 0.046), with no difference in mortality (p = 0.56), compared to patients experiencing BiV pacing <98%. There was no difference in mortality among patients with or without VAs after CF-LVAD [5 patients (27.8%) vs. 14 patients (27.5%), p = 0.18)], and patients with or without previous history of VAs (p = 0.95). Also, there was no difference in mortality among patients with a different timing of implant of implantable cardioverter-defibrillator (ICD), before and after CF-LVAD (p = 0.11). CONCLUSIONS: VAs in CF-LVAD are a common clinical problem, but they do not impact mortality. Timing of ICD implantation does not have a significant impact on patients' survival. Patients with BiV pacing ≥98% experienced more frequently VAs.

Genetic background of mitral valve prolapse.

Mitral valve prolapse (MVP) has a prevalence of 2-3% among the population. It involves a heterogeneous group of patients with different expressions and according to the phenotype can be further divided into fibroelastic deficiency, which is mainly considered as a degeneration due to aging, and myxomatous disease, frequently associated with familiar clusters. Thus, MVP can be present in syndromic, when part of a well-defined syndrome, and non-syndromic forms. The latter occurs more often. To the second belong both familiar and isolated or sporadic forms. On one hand, among familial forms, although X-linked transmission related to FLNA gene was initially identified, further studies reported also autosomal dominant mode involving MVPP genes, including DCHS1. On the other hand, genome-wide association studies (GWAS), among unrelated patients, allowed the identification of new MVP-associated genes, such as LMCD1, GLIS, and TNS1. Moreover, single nucleotide polymorphisms (SNPs) on metalloproteinase genes have been related to MVP. Interestingly some genes such as DCHS1 and DZIP1 have been reported to be involved in both familiar and isolated forms. The present review aims to illustrate the updated genetic background of MVP.

SCN5A mutation in Brugada syndrome is associated with substrate severity detected by electrocardiographic imaging and high-density electroanatomic mapping.

BACKGROUND: Brugada syndrome (BrS) is caused by mutations in SCN5A gene in 15%-20% of cases. Previous studies showed worse prognosis in SCN5A mutation carriers (SCN5A+). To date, there are no data on genotype-phenotype correlation with electrocardiographic (ECG) imaging (ECGI) and high-density epicardial electroanatomic map. OBJECTIVE: This study aimed to correlate SCN5A mutation with substrate severity in BrS assessed by ECGI and high-density electroanatomic map. METHODS: All consecutive BrS patients undergoing ECGI and high-density epicardial electroanatomic map with HD Grid Mapping Catheter were retrospectively analyzed. On ECGI, the following parameters were analyzed before and after ajmaline administration: right ventricular outflow tract (RVOT) activation time (RVOT-AT) and RVOT recovery time (RVOT-RT). On electroanatomic map, the parameters analyzed before and after ajmaline were high-frequency potential activation time (HFPat), high-frequency potential duration (HFPd), high-frequency potential amplitude (HFPa), low-frequency potential activation time (LFPat), low-frequency potential duration (LFPd), and low-frequency potential amplitude (LFPa). RESULTS: Thirty-nine BrS patients with ECGI were included. Eight patients (20.5%) were SCN5A+. At baseline ECGI map, mean RVOT-RT was longer in SCN5A+ (P = .024). After ajmaline administration, SCN5A+ patients showed longer RVOT-AT (125.6 vs 100.8 ms; P = .045) and longer RVOT-RT (426.4 vs 397 ms; P = .033). After ajmaline administration, SCN5A+ showed longer HFPat (164.1 vs 119.5 ms; P = .041); longer LFPat (272.7 vs 200.5 ms; P = .018); and longer LFPd (211.9 vs 151.2 ms; P = .033). CONCLUSION: In BrS, SCN5A+ patients compared with SCN5A- patients exhibit marked depolarization and repolarization abnormalities as assessed by ECGI and epicardial high-density electroanatomic map.

Ajmaline-Induced Abnormalities in Brugada Syndrome: Evaluation With ECG Imaging.

Background The rate of sudden cardiac death (SCD) in Brugada syndrome (BrS) is ≈1%/y. Noninvasive electrocardiographic imaging is a noninvasive mapping system that has a role in assessing BrS depolarization and repolarization abnormalities. This study aimed to analyze electrocardiographic imaging parameters during ajmaline test (AJT). Methods and Results All consecutive epicardial maps of the right ventricle outflow tract (RVOT-EPI) in BrS with CardioInsight were retrospectively analyzed. (1) RVOT-EPI activation time (RVOT-AT); (2) RVOT-EPI recovery time, and (3) RVOT-EPI activation-recovery interval (RVOT-ARI) were calculated. ∆RVOT-AT, ∆RVOT-EPI recovery time, and ∆RVOT-ARI were defined as the difference in parameters before and after AJT. SCD-BrS patients were defined as individuals presenting a history of aborted SCD. Thirty-nine patients with BrS were retrospectively analyzed and 12 patients (30.8%) were SCD-BrS. After AJT, an increase in both RVOT-AT [105.9 milliseconds versus 65.8 milliseconds, P<0.001] and RVOT-EPI recovery time [403.4 milliseconds versus 365.7 milliseconds, P<0.001] was observed. No changes occurred in RVOT-ARI [297.5 milliseconds versus 299.9 milliseconds, P=0.7]. Before AJT no differences were observed between SCD-BrS and non SCD-BrS in RVOT-AT, RVOT-EPI recovery time, and RVOT-ARI (P=0.9, P=0.91, P=0.86, respectively). Following AJT, SCD-BrS patients showed higher RVOT-AT, higher ∆RVOT-AT, lower RVOT-ARI, and lower ∆RVOT-ARI (P<0.001, P<0.001, P=0.007, P=0.002, respectively). At the univariate logistic regression, predictors of SCD-BrS were the following: RVOT-AT after AJT (specificity: 0.74, sensitivity 1.00, area under the curve 0.92); ∆RVOT-AT (specificity: 0.74, sensitivity 0.92, area under the curve 0.86); RVOT-ARI after AJT (specificity 0.96, sensitivity 0.58, area under the curve 0.79), and ∆RVOT-ARI (specificity 0.85, sensitivity 0.67, area under the curve 0.76). Conclusions Noninvasive electrocardiographic imaging can be useful in evaluating the results of AJT in BrS.