Leonardo Calò

Risk stratification in individuals with the Brugada type 1 ECG pattern without previous cardiac arrest: usefulness of a combined clinical and electrophysiologic approach

Aims Risk stratification in individuals with type 1 Brugada electrocardiogram (ECG) pattern (type 1 ECG) for primary prevention of sudden death (SD). Methods and results Three hundred and twenty patients (258 males, median age 43 years) with type 1 ECG were enrolled. No patient had previous cardiac arrest. Fifty-four per cent of patients had a spontaneous and 46% a drug-induced type 1 ECG. One-third had syncope, two-thirds were asymptomatic. Two hundred and forty-five patients underwent electrophysiologic study (EPS) and 110 patients received an implantable cardiac defibrillator (ICD). During follow-up [median length 40 months (IQ20-67)], 17 patients had major arrhythmic events (MAE) (14 resuscitated ventricular fibrillation (VF) and three SD). Both a spontaneous type 1 ECG and syncope significantly increased the risk (2.6 and 3.0% event rate per year vs. 0.4 and 0.8%). Major arrhythmic events occurred in 14% of subjects with positive EPS, in no subjects with negative EPS and in 5.3% of subjects without EPS. All MAE occurred in subjects who had at least two potential risk factors (syncope, family history of SD, and positive EPS). Among these patients, those with spontaneous type 1 ECG had a 30% event rate. Conclusion (1) In subjects with the Brugada type 1 ECG, no single clinical risk factor, nor EPS alone, is able to identify subjects at highest risk; (2) a multiparametric approach (including syncope, family history of SD, and positive EPS) helps to identify populations at highest risk; (3) subjects at highest risk are those with a spontaneous type 1 ECG and at least two risk factors; (4) the remainder are at low risk.

Limited posterior left atrial cryoablation in patients with chronic atrial fibrillation undergoing valvular heart surgery

OBJECTIVES We sought to evaluate whether a limited surgical cryoablation of the posterior region of the left atrium was safe and effective in the cure of atrial fibrillation (AF) in patients with associated valvular heart disease. BACKGROUND Extensive surgical ablation of AF is a complex and risky procedure. The posterior region of the left atrium seems to be important in the initiation and maintenance of AF. METHODS In 32 patients with chronic AF who underwent heart valve surgery, linear cryolesions connecting the four pulmonary veins and the posterior mitral annulus were performed. Eighteen patients with AF who underwent valvular surgery but refused cryoablation were considered as the control group. RESULTS Sinus rhythm (SR) was restored in 25 (78%) of 32 patients immediately after the operation. The cryoablation procedure required 20 +/- 4 min. There were no intraoperative and perioperative complications. During the hospital period, one patient died of septicemia. Thirty-one patients reached a minimum of nine months of follow-up. Two deaths occurred but were unrelated to the procedure. Twenty (69%) of 29 patients remained in SR with cryoablation alone, and 26 (90%) of 29 patients with cryoablation, drugs and radiofrequency ablation. Three (10%) of 29 patients remained in chronic AF. Right and left atrial contractility was evident in 24 (92%) of 26 patients in SR. In control group, two deaths occurred, and SR was present in only four (25%) of 16 patients. CONCLUSIONS Linear cryoablation with lesions connecting the four pulmonary veins and the mitral annulus is effective in restoration and maintenance of SR in patients with heart valve disease and chronic AF. Limited left atrial cryoablation may represent a valid alternative to the maze procedure, reducing myocardial ischemic time and risk of bleeding.

Effectiveness of remote monitoring of CIEDs in detection and treatment of clinical and device-related cardiovascular events in daily practice: the HomeGuide Registry.

Aims The HomeGuide Registry was a prospective study (NCT01459874), implementing a model for remote monitoring of cardiac implantable electronic devices (CIEDs) in daily clinical practice, to estimate effectiveness in major cardiovascular event detection and management. Methods and results The workflow for remote monitoring [Biotronik Home Monitoring (HM)] was based on primary nursing: each patient was assigned to an expert nurse for management and to a responsible physician for medical decisions. In-person visits were scheduled once a year. Seventy-five Italian sites enrolled 1650 patients [27% pacemakers, 27% single-chamber implantable cardioverter defibrillators (ICDs), 22% dual-chamber ICDs, 24% ICDs with cardiac resynchronization therapy]. Population resembled the expected characteristics of CIED patients. During a 20 ± 13 month follow-up, 2471 independently adjudicated events were collected in 838 patients (51%): 2033 (82%) were detected during HM sessions; 438 (18%) during in-person visits. Sixty were classified as false-positive, with generalized estimating equation-adjusted sensitivity and positive predictive value of 84.3% [confidence interval (CI), 82.5–86.0%] and 97.4% (CI, 96.5–98.2%), respectively. Overall, 95% of asymptomatic and 73% of actionable events were detected during HM sessions. Median reaction time was 3 days [interquartile range (IQR), 1–14 days]. Generalized estimating equation-adjusted incremental utility, calculated according to four properties of major clinical interest, was in favour of the HM sessions: +0.56 (CI, 0.53–0.58%), P < 0.0001. Resource consumption: 3364 HM sessions performed (76% by nurses), median committed monthly manpower of 55.5 (IQR, 22.0–107.0) min × health personnel/100 patients. Conclusion Home Monitoring was highly effective in detecting and managing clinical events in CIED patients in daily practice with remarkably low manpower and resource consumption.

Different patterns of atrial activation in idiopathic atrial fibrillation: simultaneous multisite atrial mapping in patients with paroxysmal and chronic atrial fibrillation

OBJECTIVES We aimed to evaluate: 1) the behavior of electrical activity simultaneously in different atrial regions during atrial fibrillation (AF); 2) the difference of atrial activation between paroxysmal and chronic AF; 3) the atrial refractoriness dispersion; and 4) the correlation between the effective refractory periods (ERPs) and the FF intervals. BACKGROUND Little data exist on the electrophysiologic characteristics of the different atrial regions in patients with AF. A more detailed knowledge of the electrical activity during AF may provide further insights to improve treatment of AF. METHODS Right and left atria were extensively mapped in 30 patients with idiopathic AF (18 paroxysmal and 12 chronic). In different atrial locations, we analyzed 1) the FF interval duration; and 2) the grade of organization and, in case of organized electrical activity, the direction of atrial activation. Furthermore, in patients with paroxysmal AF, we determined the atrial ERP, evaluated the ERP dispersion and assessed the presence of a correlation between the ERPs and the FF intervals. RESULTS In patients with chronic AF, we observed a shortening of the FF intervals and a greater prevalence of disorganized activity in all the atrial sites examined. In patients with paroxysmal AF, a significant dispersion of refractoriness was observed. The right lateral wall showed longer FF intervals and more organized atrial activity and, unexpectedly, the shortest mean ERPs. In contrast, the septal area showed shorter FF intervals, greater disorganization and the longest mean ERPs. CONCLUSIONS Electrical activity during AF showed a significant spatial inhomogeneity, which was more evident in patients with paroxysmal AF. The mean FF intervals did not correlate with the mean ERPs.

n-3 Polyunsaturated fatty acids for the prevention of arrhythmia recurrence after electrical cardioversion of chronic persistent atrial fibrillation: a randomized, double-blind, multicentre study

AIMS Persistent atrial fibrillation (AF) often recurs after direct current electrical cardioversion (ECV). As several experimental and clinical studies suggest that n-3 polyunsaturated fatty acids (PUFAs) may have antiarrhythmic properties even at the atrial level, we aimed to evaluate whether oral supplementation with PUFAs, in addition to conventional antiarrhythmic drugs, could reduce the recurrence rate of the arrhythmia after ECV of persistent AF. METHODS AND RESULTS Two hundred and four patients (mean age 69.3 years, 33% females) with persistent AF were randomly assigned to receive 3 g/day of PUFAs until ECV and 2 g/day thereafter (104 patients) or placebo (100 patients) for 6 months, beginning at least 1 week before ECV. Selection of conventional antiarrhythmic prophylaxis was left to local medical advice. The cardiac rhythm was assessed by both trans-telephonic monitoring and clinical visits. Primary end-point was the recurrence rate of AF. Sinus rhythm was restored, either spontaneously or after ECV, in 187 patients (91.7%); 95 patients (91.4%) on PUFAs and 92 patients (92.0%) on placebo (P=not significant). AF relapsed in 56 (58.9%) of the PUFAs patients and in 47 (51.1%) of the placebo patients (P=0.28). The mean time to AF recurrence was 83±8 days in the PUFAs group and 106±9 days in the placebo group (P=0.29). CONCLUSION Our results do not support the hypothesis that, in patients undergoing ECV of chronic persistent AF, supplementation with PUFAs in addition to the usual antiarrhythmic treatment reduces recurrent AF.

Efficacy of ivabradine administration in patients affected by inappropriate sinus tachycardia

BACKGROUND Inappropriate sinus tachycardia (IST) is characterized by an elevated heart rate (HR) at rest and an exaggerated HR response to physical activity or emotional stress. Beta-blockers and calcium channel blockers are the first-line therapy but sometimes are poorly tolerated due to side effects. OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of ivabradine, a selective inhibitor of the I(f) current of the sinoatrial node, in patients affected by IST. METHODS Eighteen consecutive symptomatic patients (2 men and 16 women; mean age 45 +/- 15 years) affected by IST were enrolled in the study. Every patient underwent resting ECG, 24-hour Holter ECG, and exercise ECG at baseline and at 3-month and 6-month follow-up. RESULTS Sixteen patients (14 women; mean age 41 +/- 14 years) completed the study. Holter ECG assessment showed a significant reduction of medium HR (P <.001) and maximal HR (P <.001, basal vs 3-6 months; P = .02, 3 vs 6 months). Minimal HR slightly decreased at 3 months and then stabilized (P = .49, 3 vs 6 months) despite an increased drug dose. Stress test showed a significant decrease at rest (P <.001) and maximal HR (P <.05), suggesting an increased tolerance to physical stress, which was confirmed by a progressive increase of maximal load reached (>100 W) during stress test at 3 months (75%) and 6 months (85%). One patient was excluded because of phosphenes despite dose lowering, and another patient did not complete the protocol. CONCLUSION Ivabradine could represent an effective and safe alternative to calcium channel blockers and beta-blockers for treatment of IST.

A New Electrocardiographic Marker of Sudden Death in Brugada Syndrome: The S-Wave in Lead I

BACKGROUND Risk stratification in asymptomatic patients remains by far the most important yet unresolved clinical problem in the Brugada syndrome (BrS). OBJECTIVES This study sought to analyze the usefulness of electrocardiographic parameters as markers of sudden cardiac death (SCD) in BrS. METHODS This study analyzed data from 347 consecutive patients (78.4% male; mean age 45 ± 13.1 years) with spontaneous type 1 BrS by ECG parameters but with no history of cardiac arrest (including 91.1% asymptomatic at presentation, 5.2% with a history of atrial fibrillation [AF], and 4% with a history of arrhythmic syncope). Electrocardiographic characteristics at the first clinic visit were analyzed to predict ventricular fibrillation (VF)/SCD during follow-up. RESULTS During the follow-up (48 ± 38 months), 276 (79.5%) patients remained asymptomatic, 39 (11.2%) developed syncope, and 32 (9.2%) developed VF/SCD. Patients who developed VF/SCD had a lower prevalence of SCN5A gene mutations (p = 0.009) and a higher prevalence of positive electrophysiological study results (p < 0.0001), a family history of SCD (p = 0.03), and AF (p < 0.0001). The most powerful marker for VF/SCD was a significant S-wave (≥0.1 mV and/or ≥40 ms) in lead I. In the multivariate analysis, the duration of S-wave in lead I ≥40 ms (hazard ratio: 39.1) and AF (hazard ratio: 3.7) were independent predictors of VF/SCD during follow-up. Electroanatomic mapping in 12 patients showed an endocardial activation time significantly longer in patients with an S-wave in lead I, mostly because of a significant delay in the anterolateral right ventricular outflow tract. CONCLUSIONS The presence of a wide and/or large S-wave in lead I was a powerful predictor of life-threatening ventricular arrhythmias in patients with BrS and no history of cardiac arrest at presentation. However, the prognostic value of a significant S-wave in lead I should be confirmed by larger studies and by an independent confirmation cohort of healthy subjects.

Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies

BACKGROUND Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to the plasmatic membrane. FLNC mutations have been associated with myofibrillar myopathies, and cardiac involvement has been reported in some carriers. Accordingly, since 2012, the authors have included FLNC in the genetic screening of patients with inherited cardiomyopathies and sudden death. OBJECTIVES The aim of this study was to demonstrate the association between truncating mutations in FLNC and the development of high-risk dilated and arrhythmogenic cardiomyopathies. METHODS FLNC was studied using next-generation sequencing in 2,877 patients with inherited cardiovascular diseases. A characteristic phenotype was identified in probands with truncating mutations in FLNC. Clinical and genetic evaluation of 28 affected families was performed. Localization of filamin C in cardiac tissue was analyzed in patients with truncating FLNC mutations using immunohistochemistry. RESULTS Twenty-three truncating mutations were identified in 28 probands previously diagnosed with dilated, arrhythmogenic, or restrictive cardiomyopathies. Truncating FLNC mutations were absent in patients with other phenotypes, including 1,078 patients with hypertrophic cardiomyopathy. Fifty-four mutation carriers were identified among 121 screened relatives. The phenotype consisted of left ventricular dilation (68%), systolic dysfunction (46%), and myocardial fibrosis (67%); inferolateral negative T waves and low QRS voltages on electrocardiography (33%); ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in 21 of 28 families). Clinical skeletal myopathy was not observed. Penetrance was >97% in carriers older than 40 years. Truncating mutations in FLNC cosegregated with this phenotype with a dominant inheritance pattern (combined logarithm of the odds score: 9.5). Immunohistochemical staining of myocardial tissue showed no abnormal filamin C aggregates in patients with truncating FLNC mutations. CONCLUSIONS Truncating mutations in FLNC caused an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies complicated by frequent premature sudden death. Prompt implantation of a cardiac defibrillator should be considered in affected patients harboring truncating mutations in FLNC.

Radiofrequency Catheter Ablation of Idiopathic Left Ventricular Outflow Tract Tachycardia: Utility of Intracardiac Echocardiography

Idiopathic LVOT Tachycardia. Introduction: The site of origin of idiopathic ventricular tachycardia (VT) arising from the left ventricular outflow tract (LVOT) may be closely related to the aortic valve leaflets, and radiofrequency (RF) delivery potentially can damage them. Intracardiac echocardiography (ICE) can identify accurately the ablation electrode and anatomic landmarks, and contact with the endocardium can be easily assessed. The aim of this study was to define the utility and the accuracy of ICE in guiding RF ablation of idiopathic VT of the LVOT.

Catheter-tissue contact force for pulmonary veins isolation: a pilot multicentre study on effect on procedure and fluoroscopy time.

Aims Catheter–tissue contact is critical for effective lesion creation in radiofrequency catheter ablation (RFCA). In a multicentre prospective study, we assessed the effect of direct contact force (CF) measurement on acute procedural parameters during RFCA of atrial fibrillation (AF). Methods and results A new open-irrigated tip catheter with CF sensing (SmartTouch™, Biosense Webster Inc.) was used. All the patients underwent the first ablation procedure for paroxysmal AF with antral pulmonary vein (PV) isolation, aiming at entry and exit conduction block in all PVs. Ninety-five patients were enroled in nine centres and successfully underwent ablation. Overall procedure time, fluoroscopy time, and ablation time were 138.0 ± 67.0, 14.3 ± 11.2, and 33.8 ± 19.4 min, respectively. The mean CF value during ablation was 12.2 ± 3.9 g. Force time integral (FTI) analysis showed that patients achieving a value below the median of 543.0gs required longer procedural (158.0 ± 74.0 vs. 117.0 ± 52.0 min, P = 0.004) and fluoroscopy (17.5 ± 13.0 vs. 11.0 ± 7.7 min, P = 0.007) times as compared with those in whom FTI was above this value. Patients in whom the mean CF during ablation was >20 g required shorter procedural time (92.0 ± 23.0 vs. 160.0 ± 67.0 min, P = 0.01) as compared with patients in whom this value was <10 g. Four groin haematomas were the only complications observed. Conclusion Contact force during RFCA for PV isolation affects procedural parameters, in particular procedural and fluoroscopy times, without increasing complications.