A Computational Study of the Electrophysiological Substrate in Patients Suffering From Atrial Fibrillation.

In the context of cardiac electrophysiology, we propose a novel computational approach to highlight and explain the long-debated mechanisms behind atrial fibrillation (AF) and to reliably numerically predict its induction and sustainment. A key role is played, in this respect, by a new way of setting a parametrization of electrophysiological mathematical models based on conduction velocities; these latter are estimated from high-density mapping data, which provide a detailed characterization of patients' electrophysiological substrate during sinus rhythm. We integrate numerically approximated conduction velocities into a mathematical model consisting of a coupled system of partial and ordinary differential equations, formed by the monodomain equation and the Courtemanche-Ramirez-Nattel model. Our new model parametrization is then adopted to predict the formation and self-sustainment of localized reentries characterizing atrial fibrillation, by numerically simulating the onset of ectopic beats from the pulmonary veins. We investigate the paroxysmal and the persistent form of AF starting from electro-anatomical maps of two patients. The model's response to stimulation shows how substrate characteristics play a key role in inducing and sustaining these arrhythmias. Localized reentries are less frequent and less stable in case of paroxysmal AF, while they tend to anchor themselves in areas affected by severe slow conduction in case of persistent AF.

Simultaneous endo-epicardial-high density mapping of ventricular tachycardia with the use of multi-electrode mapping catheters.

We herein describe a case of VT in an ischemic cardiomyopathy patient utilizing a novel technique of simultaneous endo-epicardial high-density mapping. Epicardial access, in addition to retrograde aortic endocardial access, was performed. Following the creation of the respective endocardial and epicardial electrical substrate maps, activation mapping of the VT was then performed simultaneously with two overlapping HD Grid catheters. Full diastolic pathway mapping was achieved, with EGMs recorded in all segments of the diastolic interval, on the epicardial surface. This case highlights the feasibility of a technique that can reliably detect the presence of activation bridges in a 3D model of VT.

European multicentre experience of staged hybrid atrial fibrillation ablation for the treatment of persistent and longstanding persistent atrial fibrillation.

The management of non-paroxysmal atrial fibrillation (AF) remains controversial. We examined the efficacy and safety of the 2 stage Hybrid AF ablation approach by analysing the largest series of this technique reported so far. METHODS: The approach aims to electrically isolate the left atrial posterior wall incorporating the pulmonary veins ('box-set'pattern). An initial video-assisted thoracoscopic (VATS) epicardial ablation is followed after a minimum of 8 weeks by endocardial radiofrequency catheter ablation. RESULTS: Of 175 patients from 4 European cardiothoracic centers, who underwent the surgical (COBRA Fusion, AtriCure Inc) 1st stage ablation, 166 went on to complete 2nd stage catheter ablation. At median follow up of 18 months post 2nd stage procedure 93/166 (56%) had remained free of AF or atrial tachycardia (AT) recurrence off antiarrhythmic drugs. 110/175 62.9% were in sinus rhythm off all antiarrhythmic drugs at last clinic follow-up (132/175 75.4% including those on antiarrhythmic drugs). 18 patients (10.8%) underwent a further re-do ablation (mean of 1.1 ablations per patient) 105/166 (63%) remained free of AF/AT recurrence off antiarrhythmic drugs following last ablation procedure.Latterly, ILRs have been implanted in patients (n = 56); 60% have remained fully arrhythmia free and 80% have shown AF burden < 5% at a median 14 months follow-up [IQR: 13.5 (8-21.5)]. Only 10.9% have reverted to persistent AF. 5 patients (2.9%) had a perioperative stroke and 4 patients (2.3%) exhibited persistent weakness of the right hemidiaphragm following stage 1 VATS epicardial ablation. One patient died following stroke (overall mortality 0.6%). CONCLUSIONS: In patients with non-paroxysmal AF with unfavourable characteristics for catheter ablation, the staged hybrid approach results in acceptable levels of freedom from recurrent atrial arrhythmia, however, complication rates are higher than with catheter ablation alone.

Updated clinical overview on cardiac laminopathies: an electrical and mechanical disease.

Cardiac laminopathies, associated with mutations in the LMNA gene, encompass a wide spectrum of clinical manifestations, involving electrical and mechanical alterations of cardiomyocytes. Thus, dilated cardiomyopathy, bradyarrhythmias and atrial or ventricular tachyarrhythmias may occur in a number of combined phenotypes. Nowadays, some attempt has been made to identify clinical predictors for the most life-threatening complications of LMNA-associated heart disease, i.e. sudden cardiac death and end-stage heart failure. The goal of this manuscript is to combine the most recent evidences in an updated review to show the state-of-the-art of such a complex disease group. This is supposed to be the starting point to collect more data and design new ad hoc studies to identify clinically useful predictors to stratify risk in mutation carriers, including probands and their asymptomatic relatives.

Rhythm-symptom correlation in patients on continuous monitoring after catheter ablation of atrial fibrillation.

INTRODUCTION: Correlation between symptoms and atrial fibrillation (AF) episodes after catheter ablation may have clinical relevance, especially for anticoagulation usage. The aim of our project was to analyze the relationship between symptoms and AF recurrences in unselected patients following AF catheter ablation during long-term follow-up. METHODS AND RESULTS: One hundred and forty-three consecutive patients (mean age 59 ± 9 years, 85% male) were implanted with a continuous cardiac monitor (RevealXT, Medtronic Inc., Minneapolis, MN, USA) following first pulmonary vein ablation procedure. Device data were downloaded every 3 months and correlated to patients' symptom diary. AF was paroxysmal in 55% and persistent in 45%. At a mean follow-up of 14 ± 6 months, 98/143 (69%) patients had at least one AF recurrence. Among these, 53 (54%) reported AF-related symptoms while 45 (46%) were totally asymptomatic. Conversely, 13 (29%) out of 45 patients without AF recurrences reported symptoms. Globally, a significant reduction of symptoms (from 82% at baseline to 44% at last follow-up; P < 0.0001) was observed. SF-12 questionnaire showed a significant improvement of physical and mental functioning (respectively 44.5 ± 8.5 vs 51.0 ± 6.7, and 45.7 ± 9.3 vs 49.2 ± 6.1, P < 0.05 baseline vs last follow-up). At the 12-month follow-up, 80% and 77% of patients were on AAD and anticoagulant drugs, respectively. There were not differences in AAD usage in symptomatic and asymptomatic patients. CONCLUSIONS: Continuous ECG monitoring is a valuable tool for long-term follow-up after AF catheter ablation facilitating reliable assessment of symptomatic and asymptomatic AF episodes. This may have clinical implications with regards to anticoagulation therapy in high-risk patients.

Non-contact left ventricular endocardial mapping for cardiac resynchronisation therapy: a "slow conduction" towards the fast solution.

Cardiac resynchronisation therapy can help to improve left ventricular function in patients with heart failure, but only if those regions of myocardium which are mostly compromised by electromechanical desynchronisation can be identified and effectively stimulated.

Atypical atrial flutter: clinical features, electrophysiological characteristics and response to radiofrequency catheter ablation.

AIMS: To evaluate the clinical and electrophysiological features of atypical atrial flutter (AAF) and its response to radiofrequency catheter ablation. METHODS AND RESULTS: In 90 consecutive patients referred for sustained atrial flutter, bipolar recordings were obtained from the tricuspid annulus, coronary sinus, interatrial septum and left atrium. AAF was defined by the absence of concealed entrainment from the inferior vena cava--tricuspid annulus isthmus. Target sites were identified by early, fragmented or double potentials and by concealed entrainment. Linear lesions were created between target sites and nearby anatomical barriers in a temperature-controlled mode: 20 episodes of AAFs were documented in 19/90 (21%) patients. Mitral valve disease and surgery were significantly more frequent in patients with AAF. Target sites were identified in the right atrial free wall (n=8), interatrial septum (n=6), left atrium (n=4) and coronary sinus (n=2). Effective ablation was obtained in 15/19 patients (79%). After a 15.7 +/- 10.7 month follow-up, AAF recurred in 0/15 patients with a successful and 3/4 (75%) with a failed procedure (P<0.05). CONCLUSIONS: Conventional mapping techniques enable identification of critical sites of AAF and allow successful ablation in the majority of cases.

Non-contact mapping to guide catheter ablation of untolerated ventricular tachycardia.

AIMS: The role of a novel non-contact mapping system (ESI 3000, Endocardial Solutions) to guide radiofrequency catheter ablation of untolerated ventricular tachycardia was investigated in 17 patients; 11 with prior myocardial infarction, three with arrhythmogenic right ventricular dysplasia, and three with idiopathic dilated cardiomyopathy. METHODS: Twenty-seven monomorphic ventricular tachycardias were induced (mean cycle 320+/-60 ms, range 230-450 ms), mapped for 15-20 s, and terminated by overdrive pacing or DC shock. Off-line analysis of isopotential activation mapping was performed to identify the diastolic pathway and/or the exit point of the ventricular tachycardia reentry circuit. Radiofrequency current was applied to create a line of block across the diastolic pathway or around the exit point. RESULTS: All 27 ventricular tachycardias were mapped with the non-contact system. The endocardial exit point (-7+/-15 ms before QRS onset) was defined in 21/21 postinfarction ventricular tachycardias, in 3/3 arrhythmogenic right ventricular dysplasia and in 1/3 idiopathic dilated cardiomyopathy ventricular tachycardias, respectively. The diastolic pathway (earliest endocardial diastolic activity: -65+/-49 ms before QRS onset) was identified in 17/21 postinfarction ventricular tachycardias, in 1/3 arrhythmogenic right ventricular dysplasia and in 1/3 idiopathic dilated cardiomyopathy ventricular tachycardias, respectively. Catheter ablation was performed in 25/27 ventricular tachycardias (93%) in 15/17 patients (88%): 16/25 ventricular tachycardias (64%) were successfully ablated in 10/17 patients (59%). Catheter ablation was not performed in two patients or proved unsuccessful in five patients. At a follow-up of 15+/-5 months, there was no recurrence of documented ventricular tachycardia in all 10 patients with successful catheter ablation; in two of them a previously non-documented ventricular tachycardia occurred. A high recurrence of ventricular tachycardia was observed in patients with a failed procedure (5/7: 71%). No major complication or death occurred. CONCLUSIONS: Non-contact mapping can be effectively used to map and guide radiofrequency catheter ablation of untolerated ventricular tachycardias. Given the favourable acute and clinical long-term results, this approach proves to be more effective in patients with postinfarction ventricular tachycardias, in comparison to patients with arrhythmogenic right ventricular dysplasia and idiopathic dilated cardiomyopathy.

Catheter ablation and antiarrhythmic drugs for haemodynamically tolerated post-infarction ventricular tachycardia; long-term outcome in relation to acute electrophysiological findings.

AIMS: Radiofrequency catheter ablation is effective at terminating ventricular tachycardia, but the overall clinical role of the technique in patients with a prior myocardial infarction is still debated, due to the uncertainties of the long-term reliability of the procedure. The purpose of this study was to prospectively investigate the relationship between acute results obtained by catheter ablation and long-term outcome in a homogeneous population of patients with post-myocardial infarction ventricular tachycardia. METHODS AND RESULTS: One hundred and twenty-four consecutive patients with recurrent, drug-refractory, haemodynamically tolerated ventricular tachycardia were included in the study. This population accounted for 30% of the patients with post-myocardial infarction ventricular tachycardia admitted between April 1992 and September 1997 to the investigating centres. The ablation was successful in eliminating sustained ventricular tachycardia in 91 of them (73%); a partial result was obtained in 21 (17%) and failure in 12 (10%). Low dose amiodarone and/or beta-blockers were maintained in 86% of the patients. Over a median follow-up of 41.5 months (interquartile range 30.5-59.5 months), there were 15 deaths (12%), three of which were sudden (2.4%); the 12 remaining patients died of heart failure. Event-free survival analysis showed a significantly lower ventricular tachycardia recurrence rate in patients with a successful procedure as compared to those with failure or a partial result (19% vs 53% at one year and 27% vs 60% at 3 years, P=0.003). A repeat procedure was performed in 15 patients with early recurrences and was followed in all by long-term success. Of those who submitted to a second procedure, 93/124 patients (75%) are free of ventricular tachycardia recurrences. An implantable cardioverter-defibrillator (ICD), following procedure failure, was implanted in 13 patients (11%) of the study population. CONCLUSIONS: Radiofrequency catheter ablation is effective in a wide population of patients with recurrent tolerated ventricular tachycardia, with very low sudden death and cardiac mortality rates over the long-term. Persistent ventricular tachycardia inducibility after catheter ablation requires an ICD implant and/or repeat ablation.

Indications for dual-chamber cardioverter defibrillators at implant and at 1 year follow-up: a retrospective analysis in the single-chamber defibrillator era.

AIM: This retrospective four-centre study assessed the current indications for dual-chamber implantable cardioverter defibrillators (ICDs) at implant and during a medium-term follow-up period in a group of patients treated by single-chamber ICD in the pre dual-chamber ICD era. METHODS AND RESULTS: The study population consisted of 153 consecutive patients (127 males, mean age 58 +/- 6 years) treated by single-chamber ICD for ventricular tachycardia and/or ventricular fibrillation. Definite indications for having a dual-chamber ICD included the presence of sinus node dysfunction and of second- or third-degree atrioventricular (AV) block, while possible indications were represented by paroxysmal atrial fibrillation or flutter and first-degree AV block. At implant, dual-chamber ICD would appear definitely indicated in 10.5% of cases, and possibly indicated in an additional 17.5% of cases. During 12 +/- 10 months follow-up, such percentages remained stable (11 and 19.5%, respectively). Inappropriate ICD intervention was documented in five of 13 patients (38%), with episodes of paroxysmal atrial fibrillation or flutter. CONCLUSION: In this non-selected study population, a dual-chamber ICD would have potentially benefited approximately 30% of the patients. During medium-term follow-up, there was no progression towards increasing dual-chamber ICD indications. The 15% cumulative incidence of paroxysmal atrial tachyarrhythmias justifies the activation of dedicated detection algorithms.

Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families.

BACKGROUND: The ECG pattern of right bundle branch block and ST-segment elevation in leads V(1) to V(3) (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups. METHODS AND RESULTS: Sixty patients (45 males aged 40+/-15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33+/-38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%). CONCLUSIONS: At variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.

Should ablation of atrial flutter be discouraged in patients with documented atrial fibrillation?

Atrial fibrillation and atrial flutter often coexist in the same patient. The purpose of this article is to provide an analysis of the mechanisms underlying the transformation from atrial fibrillation into atrial flutter and to investigate the long-term clinical benefits following ablation of atrial flutter in relation to recurrences of atrial fibrillation. Experimental studies in the human atrium demonstrated that in most instances atrial fibrillation is a triggering rhythm for atrial flutter. However, a review of the most recent studies shows a low percentage of recurrence of atrial fibrillation after successful catheter ablation for atrial flutter. The risk factors for this recurrence are the presence of structural heart disease, increased left atrial dimension and volume, a previous history of atrial fibrillation, and the failure of multiple antiarrhythmic drugs, inducibility of atrial fibrillation by a standard programmed electrical stimulation protocol after catheter ablation. These data, together with the high success rate of catheter ablation for atrial flutter, suggest to perform radiofrequency catheter ablation for atrial flutter in patients with documented atrial fibrillation.

Radiofrequency ablation of atrioventricular junction and pacemaker implantation versus modulation of atrioventricular conduction in drug refractory atrial fibrillation.

Modulation of atrioventricular (AV) node conduction and radiofrequency ablation of AV junction are alternative approaches to control ventricular rate in drug refractory atrial fibrillation (AF). In 2 centers, 120 patients were treated either with AV junction ablation (center 1, group 1, 60 patients [30 men, aged 64 +/- 11 years], paroxysmal AF in 24 patients) or with modulation (group 2, 60 patients [32 men, aged 58 +/- 12 years], paroxysmal AF in 43 patients). In group 1, complete AV block was achieved in all patients. In group 2, the procedure was performed in sinus rhythm (30 patients), prolonging the Wenckebach cycle length from 328 +/- 85 to 466 +/- 80 ms (p <0.01) or during AF (30 patients), decreasing ventricular rate from 178 +/- 35 to 96 +/- 35 beats/min (p <0.01), and to <100 beats/min in 17 patients (61%). Complete AV block was induced in 9 of 60 patients (15%). In groups 1 and 2, at a follow-up of 27 +/- 7 and 26 +/- 6 months, there were 2 deaths (1 cardiac, 1 sudden death) and 1 death for end-stage heart failure, respectively. Hospital readmissions decreased from 3.2 to 0.2 and from 4.2 to 0.2/year; late AF recurrences at of >120 beats/min were documented in 6% and 12%, respectively. Symptom score analysis including effort and rest dyspnea, exercise intolerance, weakness, and palpitation showed a significant improvement in both treatment groups, when acutely effective, in patients with paroxysmal and/or chronic AF. In conclusion, ablation of the AV junction shows a higher acute success rate compared with modulation of the AV node conduction in patients with drug refractory AF. Depending on the acute success, both approaches therefore were similarly effective in achieving long-term ventricular rate control and symptom score improvement.

Modulation of the atrioventricular node conduction to achieve rate control in patients with atrial fibrillation: long-term results.

Modulation of the AV node reduces the ventricular rate during AF, without affecting AV conduction during sinus rhythm. Acute and long-term results of AV node modulation in 75 patients with AF and severe related symptoms of heart failure are presented in this study. The procedure involved, in all cases, the selective ablation of the posterior inputs to the AV node; in a subgroup of 15 patients with poor modification of AV conduction properties, a sequential approach involving subsequent anterior input ablation was performed. The procedure caused acutely a prolongation of the Wenckebach cycle length (38 patients in sinus rhythm) from 334 +/- 88 to 470 +/- 80 ms (P < 0.01), and a reduction of the average ventricular rate (37 patients in AF) from 154 +/- 31 to 88 +/- 40 beats/min (P < 0.01); permanent complete AV block was induced in 9 of 75 patients (12%). Considering the "sequential" approach, an increase of the Wenckebach cycle length from 362 +/- 50 to 530 +/- 45 ms (P < 0.01) and a reduction of the average heart rate in patients with AF from 158 +/- 16 to 81 +/- 20 beats/min (P < 0.01) was obtained in this subgroup of patients, in whom the AH interval prolonged from 93 +/- 12 to 175 +/- 27 ms, and no complete AV block was observed. At a mean follow-up of 23 +/- 9 months (range 2-48), the mean number of hospital admissions per patient per year decreased from 4.2 to 0.2. Five of 49 patients with paroxysmal AF and 3 of 26 patients with chronic AF had high rate recurrences (1 > 120 beats/min) that caused severe palpitations; these patients were considered as late clinical failures (8/75; 11%). All patients reported a substantial subjective improvement and an increased exercise tolerance, as documented by a semiquantitative questionnaire. There were no episodes of late AV block or sudden cardiac deaths. In conclusion, modulation of the AV node--either by slow pathway ablation, or by a "sequential" posterior and anterior approach in refractory patients--allows a long-term control of the ventricular rate and prevents the recurrence of severe clinical symptoms in more than 75% of patients with drug refractory AF.

Incidence and clinical significance of transformation of atrial fibrillation to atrial flutter in patients undergoing long-term antiarrhythmic drug treatment.

AIMS: To investigate the rate of transformation of atrial fibrillation to atrial flutter in patients taking antiarrhythmic drugs for the prophylaxis of atrial fibrillation, we retrospectively analysed data from 305 consecutive patients with paroxysmal atrial fibrillation (155 male; mean age 63 +/- 11 years) treated with ventricular rate controlling drugs, antiarrhythmic drugs, or without drugs. METHODS AND RESULTS: At a mean follow-up of 9 months (range 1-24) all patients experienced recurrence of arrhythmia: 48 (14.6%, Group A) suffered Type 1 atrial flutter, and 257 (85.4%, Group B) atrial fibrillation. The relative rate of recurrence of atrial flutter vs atrial fibrillation was similar in patients without treatment or with ventricular rate controlling drugs (from 6.8% to 14.6%, P=ns). However, recurrence was higher (25%) in patients administered antiarrhythmic drug therapy. The relative risk in these patients was 3.02 times greater, compared with patients without treatment, or treated with rate controlling drugs (P<0.001). There were no differences between groups concerning the baseline clinical characteristics and the clinical consequences of the recurrence; patients with atrial flutter had a lower rate of conversion to sinus rhythm (42% vs 64%) and a higher rate of hospital admission (69% vs 36%) compared with those with atrial fibrillation. Six patients (8.5%) experienced 1:1 atrioventricular conduction during atrial flutter with a ventricular rate of 240-280 beats x min(-1). CONCLUSION: Our data suggest that the use of antiarrhythmic drugs for the prophylaxis of atrial fibrillation is associated with a threefold increase in the probability of Type 1 atrial flutter recurrence, as opposed to atrial fibrillation, which may have important clinical consequences, but which did not in our study.

Hypertrophic cardiomyopathy with apical aneurysm: a case of catheter and surgical therapy of sustained monomorphic ventricular tachycardia.

The case is presented of a patient with hypertrophic cardiomyopathy, midventricular obstruction, apical aneurysm, and very frequent episodes of sustained monomorphic ventricular tachycardia (VT) unresponsive to common antiarrhythmic drugs. Left ventricular catheter mapping during sinus rhythm suggested the presence of an extensively scarred apical region; early fractionated ECGs were recorded at the neck of the aneurysm during monomorphic VT, suggesting a possible role of this region as VT substrate. Radiofrequency delivery at these sites stopped the VT and it was no longer inducible; however, it spontaneously recurred the following day. An apical aneurysmectomy, guided by the results of catheter mapping, was performed and was successful in preventing arrhythmic recurrences during 12 months' follow up.