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Purpose: The aim of the study was to investigate the effect of wide area circumferential radiofrequency catheter ablation (WACA) pulmonary vein isolation on left atrium (LA) geometry. Methods: Seventy-one patients underwent WACA, for recurrent paroxysmal (n = 31) and persistent (n = 40) atrial fibrillation (AF). A three-dimension rotational angiography of the LA was obtained immediately prior to index and repeat procedure. Results: Significant reduction of LA volume (65.6 ± 14 mL/m2 vs. 62.2 ± 15 mL/m2, p < 0.001) and surface (74.4 ± 11.2 vs. 70.4 ± 11.2 cm2/m2, p < 0.001) was noted. LA sphericity increased significantly (82 ± 2% vs. 83 ± 2%, p = 0.004) in all 71 patients. Patients with paroxysmal AF showed significant reduction of LA volume (121.8 ± 25.7 vs. 116 ± 32 mL, p = 0.008) and increase of LA sphericity (82.3 ± 2.1 vs. 83.1 ± 2%, p = 0.009). Patients with persistent AF showed significant decrease of LA volume (133.5 ± 32 vs. 126 ± 32 mL, p = 0.005) and LA surface area (76.3 ± 12.3 vs. 71.8 ± 12.4 cm2/m2, p = 0.005). LA sphericity (82.4 ± 2.8 vs. 83 ± 2.4%, p = ns) remained unchanged. Conclusions: WACA results into significant reduction of LA volume and surface area. Increased LA sphericity is observed in paroxysmal AF only.

Background: Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular (LV) filling pressures and left atrial (LA) phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce. Objective: To assess relationship between the LAS and the probability of HFpEF in patients with dyspnea and paroxysmal AF. Methods: The study included 205 consecutive patients (62 ± 10 years, 58% males) with dyspnea (NYHA≥II), paroxysmal AF and preserved LV ejection fraction (≥50%), who underwent speckle tracking echocardiography during sinus rhythm. Probability of HFpEF was estimated using H2FPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides. Results: Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e’, pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p < 0.05). All components of LAS and LA strain rate showed proportional impairment with increasing probability of HFpEF (all p < 0.05). Out of the speckle tracking-derived parameters, reservoir LAS showed the largest area under the curve (AUC = 0.78, p < 0.001) and the strongest independent predictive value (OR: 1.22, 95% CI 1.08–1.38) to identify patients with high probability of HFpEF. Conclusions: Reservoir LAS shows a high diagnostic performance to distinguish HFpEF from non-cardiac causes of dyspnea in symptomatic patients with paroxysmal AF.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): International PhD Program in Cardiovascular Pathophysiology and Therapeutics CardioPaTh Background Radio-frequency catheter ablation (CA) is associated with changes of left atrial (LA) structure and function. However, the data on the accuracy of automated analysis of LA strain (LAS) are unavailable. Therefore, the aim of the present study was to compare automated with manual LAS analysis in patients with atrial fibrillation (AF) undergoing CA during sinus rhythm. Methods We prospectively enrolled 36 consecutive patients (age: 62 ± 22 years, 33% female) with symptomatic AF and preserved left ventricular (LV) ejection fraction (≥50%) undergoing the CA during sinus rhythm. All patients underwent comprehensive echocardiography at 1-day pre-CA and at 1-day post-CA. Reservoir and contractile LAS were assessed using both the automated and the manual technique as average of segmental values in apical four-chamber (4CH) view using the onset of QRS as a reference point. Results Radio-frequency CA was associated with significant decrease in magnitude of reservoir and contractile LAS in all patients, and increase in LA end-systolic (max) and end-diastolic (min) volume index (all p Conclusion The AutoStrain-derived LAS analysis showed a high correlation with manual LAS analysis. Moreover, the AutoStrain technique was associated with significantly shorter analysis time and lower interobserver variability compared with the manual technique. Abstract Figure.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): International PhD Program in Cardiovascular Pathophysiology and Therapeutics CardioPaTh Background Radio-frequency catheter ablation (CA) is associated with changes of left atrial (LA) structure and function. However, there is limited knowledge regarding the long-term impact of successful CA on atrial morphology and mechanics. Purpose To compare the time course of LA and right atrial (RA) performance in patients with paroxysmal atrial fibrillation (AF) undergoing the first CA. Methods This prospective study included 89 consecutive patients (age:62 ± 21 years; 66% male) with a history of symptomatic AF who underwent successful CA. All patients maintained SR during follow-up. A comprehensive echocardiographic examination was performed 1- day before and 1-day, 3-month and 12-month after CA. The reservoir and contractile strain for both LA and RA (LAS, RAS), and left intra-atrial mechanical dispersion (LAMD) were assessed using 2D speckle tracking echocardiography in all three apical views (only 4CH view for RAS and LAMD). Results At baseline, all patients with paroxysmal AF showed a significant reduction of reservoir and contractile LAS and RAS compared with controls (all p Conclusion Although the radio-frequency CA affected negatively LA performance in the acute phase, it has a long-term positive impact on both left and right atrial function. Figure Time course of reservoir and contractile LAS and RAS at Baseline, 1-day, 3-month and 12-month follow-up. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Background Speckle Tracking Echocardiography (STE) provides a comprehensive and quantitative assessment of myocardial function. However, the accuracy of STE-derived indices to predict maintenance of sinus rhythm (SR) following radio-frequency catheter ablation (CA) is still under debate. Therefore, the aim of the present study is to define the accuracy of STE-derived parameters to predict long-term maintenance of SR in patients with paroxysmal AF undergoing CA. Methods We prospectively enrolled 218 consecutive patients (age: 62 ± 10 years, 30% females) with paroxysmal AF undergoing first-CA. All patients with preserved ejection fraction (EF ≥ 50%) underwent comprehensive transthoracic echocardiography at baseline, including assessment of left ventricular (LV) global longitudinal strain (GLS), left atrial (LA) reservoir strain (LASr), LA conduit strain (LAScd) and LA contractile strain (LASct) using two-dimensional STE in apical views. Results At 12 months follow up, a total of 39 (18%) patients had a documented recurrence of AF. Among imaging parameters, LASr > 23% showed the largest area under the curve (0.80) to predict long-term maintenance of SR with sensitivity of 79% and specificity of 72%. Other parameters of LA function, LA diameter, maximum or minimum LA volume index, LV GLS or ejection fraction, and indices of LV diastolic function had lower area under the curve (Figure 1). Using multi-variable logistic regression, LASr (OR 1.19, 95% CI 1.10-1.23, p Conclusion In patients with paroxysmal AF undergoing radio-frequency CA, preserved LA reservoir and contractile strain is independently associated with long-term maintenance of SR, whereas LA diameter or volumes were not. LA strain may therefore be useful in management of patients with paroxysmal AF. Figure 1: Receiver-operating characteristic curves of left atrial reservoir strain (LASr), LA conduit strain (LAScd), LA contractile strain (LASct), LA emptying fraction (LAEF), LA expansion index (LAEI), LA end-systolic (LAES) and end-diastolic (LAED) volume index (VI) to predict long-term maintenance of sinus rhythm. Abstract Figure.

Background Atrial structural and functional changes may develop as a result of catheter ablation (CA) in patients with paroxysmal and persistent atrial fibrillation (AF). However, the relation between AF recurrence and atrial performance following CA is still under debate. Our aim is to describe the long-term effects of CA on LA remodeling and its correlates to the maintenance of sinus rhythm (SR). Methods We prospectively enrolled 178 consecutive patients (age: 63±9 years, 35% females) with paroxysmal AF undergoing first-CA (67%) or redo-CA (22%), and 20 individuals (11%) with long-standing persistent AF (PAF) undergoing first CA. All patients underwent comprehensive transthoracic echocardiography at baseline and at 12-month follow-up, including the assessment of reservoir and contractile strain (LAS) using two dimensional speckle tracking echocardiography in all three apical views. The study population was divided in two sub-groups according to AF recurrence during follow-up. Results During one-year follow-up, 144 (81%) patients maintained SR whereas 34 (19%) patients had AF recurrence [first-CA group 16 (13%), redo-CA group 8 (20%) and PAF group 10 (50%)]. Improvement of LAS was observed only in patients with paroxysmal and long-standing persistent AF who underwent the first CA and who remained in SR (Figure 1A, 1C). In contrast, recurrent AF was associated with absence of LAS improvement (Figure 1A, 1C). Different time course of LA performance was observed in the redo-CA group, i.e. LAS remained unchanged from baseline regardless of long-term maintenance of SR (Figure 1B). Moreover, at follow-up, no significant differences in LAS between redo-CA patients with SR versus AF were observed. Of note, in patients with long-standing persistent AF and SR, follow-up LAS increased to values observed in the redo-CA group. Conclusion LA performance following CA is strongly affected by complex interplay between extent of atrial electro-structural remodeling and CA procedure. Repeated wide CA might affects negatively LA compliance and contractility despite SR restoration. Figure 1. Reservoir and contractile LAS at Baseline and 12-month follow-up in the First-CA (1A), the Redo-CA (1B) and the long-standing persistent AF (1C) groups in patients who maintained SR versus patients who had AF recurrence. *p value Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh).

Background Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular filling pressures and left atrial phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce. Objective To assess relationship between LAS and probability of HFpEF in patients with dyspnea and paroxysmal AF. Methods The study included 205 consecutive patients (62±10 years, 58% males) with limiting dyspnea (NYHA ≥ II), paroxysmal AF and preserved LVEF (≥50%), who underwent speckle tracking echocardiography and natriuretic peptide (NT-proBNP) assessment during sinus rhythm. Patients with manifest ischemic heart or valve disease, and cardiomyopathy were excluded. Probability of HFpEF was estimated using H2FPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides. Results A total of 61 (30%), 115 (56%) and 29 (14%) had respectively high, intermediate and low probability of HFpEF. Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e', pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p Conclusions Reservoir LAS shows a strong independent association with probability of HFpEF in patients with dyspnea and paroxysmal AF. This advocates for more liberal use of LAS assessment to distinguish cardiac from non-cardiac dyspnea in patients with history of AF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh).

Introduction: We sought to investigate the net effect of wide area circumferential radiofrequency catheter ablation (WACA) on the atrial (LA) geometry. Methods and results: Seventy-one patients, who underwent a second PVI procedure, after index procedure of point-by-point WACA, for recurrent paroxysmal (n=31) or persistent (n=40) atrial fibrillation (AF) in our center were included. A three-dimension rotational angiography of the left atrium (3D-RA) under rapid ventricular pacing was performed immediately before ablation, at index and repeat ablation in all patients. LA geometry in terms of volume, sphericity and surface were assessed in all patients between first and second PVI. There was a statistical significant reduction of the LA volume (65,6 ± 14 ml/m2 vs 62,2 ± 15 ml/m2, p

Background Radio-frequency catheter isolation of pulmonary veins (RF-PVI) is associated with changes of left atrial (LA) structure and function. However, there is limited knowledge regarding the long-term impact of successful RF-PVI on the LA mechanics. The aim of the current study was to assess the time course of LA performance in patients with paroxysmal atrial fibrillation (pAF) undergoing RF-PVI. Methods The study population included 24 consecutive patients (age:62 ± 21 years; 66% male) with symptomatic pAF and preserved left ventricular ejection fraction (≥50%) undergoing the first RF-PVI and 23 healthy controls. A comprehensive echocardiographic examination was performed one day before and 1 day, 3- and 12- months after RF-PVI. The reservoir, conduit and contractile LA strain (LAS), strain rate (LASR) and mechanical dispersion (LAMD) were assessed using two-dimensional speckle tracking echocardiography in apical views. Results At baseline, patients with pAF showed a significant reduction of all three components of LAS and LASR compared with controls (all p Conclusion Successful RF-PVI is associated with acute decrease in LAS, followed by recovery to baseline values within 3 months and further improvement during one year. Reservoir and contractile LAS appears to be the most clinically useful indices to monitor LA performance in patients with pAF undergoing RF-PVI. Figure Time course of LA reservoir and contractile strain, LA max and min volume index, and LA mechanical dispersion (Baseline, 1-day FUP, 3- and 12-month FUP). Abstract 1039 Figure.

Background Atrial mechanical dispersion (MD) might increase the risk of atrial fibrillation (AF). However, the data on atrial mechanical dispersion in patients with AF undergoing catheter ablation (CA) are scarce. Purpose To describe effects of CA on inter- and left intra-atrial MD in patients with different sub-types of AF undergoing CA. Methods We prospectively enrolled 138 symptomatic patients (age: 63 ± 21 years, 32% females) with paroxysmal AF undergoing first (81%) or redo (19%) CA during sinus rhythm, and 20 individuals (age: 66 ± 23 years, 20% females) with long-standing persistent AF undergoing first CA during AF. All patients had normal (≥50%) left ventricular ejection fraction. Control group consisted of 23 healthy controls. The atrial strain and strain rate (SR) were assessed using the two-dimensional speckle tracking echocardiography as average of segmental values in all apical views for LA and in four chamber (4CH) apical view for RA. We quantified inter-atrial MD as the standard deviation of time from the onset of the P wave to peak negative strain curves (Figure 1), and left intra-atrial MD as the standard deviation of time from the onset of QRS wave to peak positive strain curves (Figure 2) of all LA segmental components in 4CH apical view after setting adjusting the reference frame to coincide with the onset of the QRS. Results Figure 3 shows a time course of reservoir LA strain and left intra-atrial MD in patients with paroxysmal AF undergoing the First-CA (3A) versus the Redo-CA (3B), and in patients with long-standing persistent AF (3C). At 1-day pre-ablation, patients with long-standing persistent AF showed significantly lower reservoir strain of both atria and higher left intra-atrial MD as compared with both paroxysmal AF groups and controls (all p Conclusion Atrial strain and MD shows distinct behavior in patients with different sub-types of AF post CA. Atrial MD may provide a complimentary information to strain when assessing LA function. Abstract 554 Figure.

Left atrium (LA) size is a well-studied predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). Yet, there is still little agreement on the best imaging technique to size the LA, and on the most appropriate sizing parameter. Volumetric assessment of LA with three-dimensional rotational angiography (3DRA LA volume index) might be a valid alternative to the commonly used transthoracic echocardiography (TTE LA volume index). The aim of our study was to investigate whether LA volume by 3DRA at the time of PVI is able to predict the risk of atrial fibrillation recurrence. We analysed 352 consecutive patients with symptomatic paroxysmal or persistent atrial fibrillation referred for PVI to our Institution. In all patients, LA volume index (LAVI) was assessed by TTE and by 3DRA. Sinus rhythm was restored after PVI in 348 patients (99%). Average TTE-LAVI and 3DRA-LAVI were 37 ± 12 and 83 ± 18 ml/m2, respectively. At a median follow-up of 19 (12, 24) months, 27% of patients had AF recurrence after the first PVI. At the univariate analysis, persistent AF (p

Background Both atrial fibrillation (AF) and catheter ablation (CA) may be associated with changes in left atrial (LA) structure and function. However, the data describing acute and short-term effects of CA on LA contractile function in different sub-types of AF are scarce. Purpose First, to describe patterns of LA structural and functional remodeling in patients with paroxysmal AF (PAF) or long-standing persistent AF (LSPAF) undergoing first or redo CA. Second, to assess clinical feasibility of LA strain and strain rate (SR) to monitor effect of AF and CA on LA contractile function. Methods We prospectively enrolled 138 consecutive patients (age: 63±21 years, 32% females) with PAF undergoing first (81%) or redo (19%) CA during sinus rhythm, and 20 individuals (age: 66±23 years, 20% females) with LSPAF undergoing first CA during AF. All patients were symptomatic and preserved (≥50%) left ventricular ejection fraction. Control group consisted of 23 healthy controls. All patients underwent comprehensive echocardiography one day pre-CA and post-CA, and at 3 month follow-up. The LA reservoir, conduit and contractile longitudinal strain (LAS) and LASR were assessed using 2D speckle tracking echocardiography as average of segmental values in apical views. Results A total of 14 (9%) patients had insufficient image quality for LA assessment and were excluded (feasibility: 91%). Pre-CA, patients with LSPAF showed the largest left atrial volume index (LAVI) (45±14 ml/m2), followed by PAF (35±8 ml/m2) and controls (24±10 ml/m2) (p Conclusion Different sub-types of AF show different patterns of LA structural and functional remodeling after CA. Both reservoir and contractile LAS appear highly feasible and reproducible to monitor LA contractile function in this clinical setting.

Background In the ICD Sports Safety Registry, death, arrhythmia- or shock-related physical injury did not occur in athletes who continue competitive sports after implantable cardioverter-defibrillator (ICD) implantation. However, data from non-competitive ICD recipients is lacking. This report describes arrhythmic events and lead performance in intensive recreational athletes with ICDs enrolled in the European recreational arm of the Registry, and compares their outcome with those of the competitive athletes in the Registry. Methods The Registry recruited 317 competitive athletes ≥ 18 years old, receiving an ICD for primary or secondary prevention (234 US; 83 non-US). In Europe, Israel and Australia only, an additional cohort of 80 ‘auto-competitive’ recreational athletes was also included, engaged in intense physical activity on a regular basis (≥2×/week and/or ≥ 2 h/week) with the explicit aim to improve their physical performance limits. Athletes were followed for a median of 44 and 49 months, respectively. ICD shock data and clinical outcomes were adjudicated by three electrophysiologists. Results Compared with competitive athletes, recreational athletes were older (median 44 vs. 37 years; p = 0.0004), more frequently men (79% vs. 68%; p = 0.06), with less idiopathic ventricular fibrillation or catecholaminergic polymorphic ventricular tachycardia (1.3% vs. 15.4%), less congenital heart disease (1.3% vs. 6.9%) and more arrhythmogenic right ventricular cardiomyopathy (23.8% vs. 13.6%) ( p Conclusions Participants in recreational sports had less frequent appropriate and inappropriate shocks during physical activity than participants in competitive sports. Shocks did not cause death or injury. Recreational athletes with ICDs can engage in sports without severe adverse outcomes unless other reasons preclude continuation.

Background: Catheter ablation is the recommended treatment in patients with paroxysmal atrial fibrillation (AF). However, the data on acute effects of catheter ablation on left atrial (LA) contractile function are scarce. Therefore, the purpose of the study was twofold:Purpose: Firstly, to describe acute effects of catheter ablation on LA contractile function in patients with paroxysmal AF and in sinus rhythm at the time of ablation. Secondly, to assess potential value of different indices of LA morphology and function. Background: Catheter ablation is the recommended treatment in patients with paroxysmal atrial fibrillation (AF). However, the data on acute effects of catheter ablation on left atrial (LA) contractile function are scarce. Therefore, the purpose of the study was twofold:Purpose: Firstly, to describe acute effects of catheter ablation on LA contractile function in patients with paroxysmal AF and in sinus rhythm at the time of ablation. Secondly, to assess potential value of different indices of LA morphology and function. ispartof: Eur Heart J vol:39 issue:suppl_1 status: Published online

Aims Intravenous administration of adenosine after a pulmonary vein (PV) isolation procedure can unmask residual, so-called ‘dormant’, conduction that would otherwise remain unnoticed. Elimination of these dormant potentials is challenging because of the transient effect of adenosine, often requiring repeated injections. We tested the hypothesis that dipyridamole, a drug which inhibits adenosine deamination, can provoke longer-lasting unmasking of dormant conduction. Methods and results In 191 patients with drug refractory paroxysmal atrial fibrillation, a bolus of 12–24 mg of adenosine was administered after all 764 PVs were isolated. In the case of transient dormant conduction, a short infusion of dipyridamole 50 mg was given and a bolus of adenosine was repeated. In all cases, re-isolation was attempted guided by the activation pattern in the PV on a circular mapping catheter. Duration of adenosine-induced dormant conduction before and after dipyridamole was recorded as the time between administration of adenosine and cessation of dormant conduction either spontaneously or by catheter ablation. Transient dormant conduction was re-established by a single bolus of adenosine in 24 of 191 patients (12.6%). Mean duration of adenosine-induced dormant conduction before dipyridamole was 13.1 ± 6.4 s, whereas it was significantly longer at 218.9 ± 165.6 s after dipyridamole ( P < 0.0001). Eighteen of the 24 PVs were re-isolated by catheter ablation before spontaneous cessation of dormant conduction, and in 6 cases dormant conduction disappeared spontaneously before PV re-isolation was achieved. Conclusion Dipyridamole significantly prolongs the effect of adenosine to unmask dormant conduction after PV isolation and may thus facilitate its elimination by catheter ablation.

Propafenone and its 5-hydroxy metabolite exhibit different electrophysiological properties. Objectives of the CAQ-PAF study were (1) to develop a strategy favoring propafenone instead of 5-hydroxypropafenone in plasma following oral administration of propafenone and (2) to evaluate the potential of low-dose quinidine to chronically inhibit CYP2D6. Patients (n = 102) with atrial fibrillation received propafenone 150 mg 3 times daily with either quinidine 100 mg twice daily or placebo. Throughout the study (follow-up, 199 ± 155 days), quinidine successfully inhibited CYP2D6: propafenone concentrations were 3 times higher in patients receiving quinidine (1033 ± 611 ng/mL vs 328 ± 229 ng/mL; P < .001). Moreover, 80% (n = 10) of patients with propafenone levels greater than 1500 ng/mL were in sinus rhythm at 1 year. In contrast, recurrence of atrial fibrillation occurred in 22 of 23 patients with propafenone levels less than 1000 ng/mL (P < .0001). Thus, chronic inhibition of CYP2D6 is achievable with low-dose quinidine in humans. Increased plasma levels of propafenone may be highly beneficial to prevent recurrence of atrial fibrillation.

Although the use of implantable cardioverter defibrillator (ICD) therapy has increased over the last decades, the reporting of ICD lead performance is inadequate. So far, there is neither a European nor worldwide registry on ICD leads. The published long-term results from national or multicentre registries encompass relatively small patient cohorts. Nevertheless, the failure of ICD leads may have substantial clinical consequences, including failure to sense, failure to pace, failure to defibrillate, inappropriate shocks, and even death of the patient. The reported ICD lead survival varies significantly between studies: 91-99% at 2 years, 85-95% at 5 years, and 60-72% at 8 years. Thus, the true incidence of lead malfunction cannot be defined as outlined in the present review. One current initiative of the European Heart Rhythm Association is to initiate and develop a Europe-wide registry to monitor, over a prolonged follow-up period, the performance of ICDs and ICD leads.

Pulsed-wave tissue Doppler imaging (TDI) was shown to predict short-term left ventricular functional recovery after cardiac resynchronization therapy (CRT). However, few data are available regarding the baseline cardiac asynchrony and clinical outcome after CRT. Therefore, we aimed to investigate the prognostic value of pre-CRT cardiac asynchrony on clinical outcome after CRT.The study population consisted of 48 consecutive patients with moderate to severe heart failure and a wide QRS complex undergoing implantation of biventricular pacemaker. Cardiac asynchrony was assessed at pulsed-wave TDI from measurements of regional electromechanical coupling times in basal segments of both ventricles (Sum asynchrony). Clinical end-points were cardiac mortality and hospitalization for worsening heart failure.During a follow-up period of 970+/-319 days, clinical end-point (9 deaths, 15 hospitalizations) occurred in 24 patients (clinical nonresponders). At baseline, responders showed higher asynchrony than nonresponders (153+/-57 ms vs. 103+/-58 ms, p0.01). Sum asynchrony of98 ms showed the highest accuracy (AUC=0.80, sensitivity 92%, specificity 67%) to identify responders. In contrast, baseline NYHA class, conventional echo-Doppler indices and QRS complex duration were similar in both groups. Eight end-point events (3 deaths) occurred in 30 patients with significant Sum asynchrony (98 ms) as compared to 16 events (6 deaths) in 18 patients with smaller Sum asynchrony (27% vs. 89%; HR 0.14; 95% CI 0.04 to 0.46; p0.001). Favorable clinical outcome was associated with larger left ventricular functional recovery at 2 years follow-up (p0.001).TDI-derived index of baseline intra- and interventricular asynchrony appears to predict long-term clinical outcome after CRT.

Objectives We studied whether functional improvement after cardiac resynchronization therapy (CRT) is associated with reversal of the heart failure (HF) gene program. Background Cardiac resynchronization therapy improves exercise tolerance and survival in patients with advanced congestive HF and dyssynchrony. Methods Twenty-four patients referred for CRT underwent left ventricular (LV) endomyocardial biopsies immediately before CRT implantation (baseline). In addition, 17 of them underwent LV endomyocardial biopsy procurement 4 months later (follow-up). In 6 control patients with normal LV function, LV biopsies were obtained at the time of coronary artery bypass grafting. The LV messenger ribonucleic acid (mRNA) levels of contractile and calcium regulatory genes were measured by quantitative real time polymerase chain reaction and normalized for glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The HF patients showing an improvement in New York Heart Association (NYHA) functional class by >1 score and a relative increase in LV ejection fraction ≥25% at 4 months after CRT were considered as responders. Results The HF patients were characterized by lower LV mRNA levels of α-myosin heavy chain (α-MHC), β-myosin heavy chain (β-MHC), sarcoplasmic reticulum calcium ATPase 2α (SERCA), phospholamban (PLN), and higher brain natriuretic peptide (BNP) mRNA levels as compared with control subjects. Responders to CRT (n = 11) showed an increase in LVEF (p Conclusions In HF patients with electromechanical cardiac dyssynchrony, functional improvement related to CRT is associated with favorable changes in established molecular markers of HF, including genes that regulate contractile function and pathologic hypertrophy.

Atrial fibrillation is the most common rhythm disturbance in clinical practice. It is a major source of stroke and morbidity. Although the Cox maze procedure effectively eliminates atrial fibrillation in most patients, the procedure has not found widespread application. As a consequence, new operations that use alternative sources of energy, such as radiofrequency, microwave, cryothermy, laser, and ultrasound have emerged to surgically create lesion sets to treat atrial fibrillation. This article reviews the fundamentals and current strategies in the surgical treatment of atrial fibrillation.

Aims Exercise-induced mitral regurgitation (MR) bears a poor prognosis in patients with congestive heart failure (CHF). Cardiac resynchronization therapy (CRT) is associated with improved clinical outcome but its effects on exercise-induced MR remain undetermined. We investigated serial changes in functional MR in relation to left ventricular (LV) remodelling and cardiopulmonary performance after CRT. Methods and results Twenty-eight patients with CHF (LV ejection fraction 25 ± 7%), broad QRS complex (171 ± 27 ms), and at least mild MR [effective regurgitant orifice (ERO) 0.25 ± 0.12 cm2] were studied with quantitative exercise echocardiography and cardiopulmonary exercise testing prior, within 1 week, and 3 months after CRT. Early after CRT, a decrease in LV dyssynchrony (from 54 ± 21 to 19 ± 7 ms, P < 0.001) and in MR at rest (ERO from 0.25 ± 0.12 to 0.20 ± 0.10 cm2, P = 0.047) was observed. However, no change in exercise-induced increase in MR was observed (ERO from 0.34 ± 0.12 to 0.31 ± 0.16 cm2, NS). Three months after CRT, a decrease in the mitral valve tenting area (from 3.3 ± 1.2 to 2.0 ± 0.6 cm2, P < 0.001) and an increase in LV sphericity index (from 1.5 ± 0.3 to 1.8 ± 0.5, P < 0.001) were paralleled by an attenuation of exercise-induced MR (ERO 0.19 ± 0.06 cm2, P = 0.001 vs. prior CRT). This was associated with an increase in LV ejection fraction (from 25 ± 7 to 35 ± 9%, P < 0.001), peak oxygen uptake (from 11.7 ± 2.4 to 13.7 ± 3.8 mL/kg/min, P = 0.001), and a decrease in Nt-pro-BNP (from 2777 ± 1681 to 1963 ± 1361 pg/mL, P = 0.067). Conclusion CRT is associated with acute decrease in resting MR but does not immediately attenuate exercise-induced MR. In contrast, only late, CRT-induced reversed LV remodelling and reduced mitral apparatus deformation are associated with a reduction in both resting and exercise-induced MR and with an improvement in cardiopulmonary performance.

Bundle Branch Reentrant Tachycardia. Introduction: We report the case of a 36-year-old patient with a longstanding history of paroxysmal tachycardia. Methods and Results: During the electrophysiological study, the H-V interval was prolonged in sinus rhythm, and a second potential (H") with distal to proximal activation pattern was recorded in the region of the proximal His-Purkinje system. Two wide QRS complex tachycardias were induced, both with V-A dissociation. One application of radiofrequency energy at the site with earliest and largest H" potential during sinus rhythm cured both tachycardias. The right and left bundle branch block morphology tachycardias were diagnosed as clockwise and counterclockwise bundle branch reentrant tachycardia. The H" potential represented the retrograde right bundle potential during sinus rhythm and bundle branch block reentrant tachycardia.

Background The aim of cardiac resynchronization therapy is correction of left ventricular (LV) dyssynchrony. However, little is known about the optimal timing of LV and right ventricular (RV) stimulation. Objectives The purpose of this study was to evaluate the acute hemodynamic effects of biventricular pacing, using a range of interventricular delays in patients with advanced heart failure. Methods Twenty patients with dilated ischemic (n = 12) and idiopathic (n = 8) cardiomyopathy (age 66 ± 6 years, New York Heart Association class III–IV, LV end-diastolic diameter >55 mm, ejection fraction 22% ± 18%, and QRS 200 ± 32 ms) were implanted with a biventricular resynchronization device with sequential RV and LV timing (VV) capabilities. Tissue Doppler echocardiographic parameters were measured during sinus rhythm before implantation and following an optimal AV interval with both simultaneous and sequential biventricular pacing. The interventricular interval was modified by advancing the LV stimulus (LV first) or RV stimulus (RV first) up to 60 ms. For each stimulation protocol, standard echocardiographic Doppler and tissue Doppler imaging (TDI) echo were used to measure the LV outflow tract velocity-time integral, LV filling time, intraventricular delay, and interventricular delay. Results The highest velocity-time integral was found in 12 patients with LV first stimulation, 5 patients with RV first stimulation, and 3 patients with simultaneous biventricular activation. Compared with simultaneous biventricular pacing, the optimized sequential biventricular pacing significantly increased the velocity-time integral ( P P = .001) and decreased interventricular delay ( P = .013) and intraventricular delay ( P = .010). The optimal VV interval could not be predicted by any clinical nor echocardiographic parameter. At 6-month follow-up, the incidence of nonresponders was 10%. Conclusion Optimal timing of the interventricular interval results in prolongation of the LV filling time, reduction of interventricular asynchrony, and an increase in stroke volume. In patients with advanced heart failure undergoing cardiac resynchronization therapy, LV hemodynamics may be further improved by optimizing LV–RV delay.

ICD implantation is standard therapy for malignant ventricular arrhythmias. The advantage of dual and single coil defibrillator leads in the successful conversion of arrhythmias is unclear. This study compared the effectiveness of dual versus single coil defibrillation leads. The study was a prospective, multicenter, randomized study comparing a dual with a single coil defibrillation system as part of an ICD using an active pectoral electrode. Seventy-six patients (64 men, 12 women; age 61 +/- 11 years) were implanted with a dual (group 1, n = 38) or single coil lead system (group 2,n = 38). The patients represented a typical ICD cohort: 60% presented with ischemic cardiomyopathy as their primary cardiac disease, the mean left ventricular ejection fraction was 0.406 +/- 0.158. The primary tachyarrhythmia was monomorphic ventricular tachyarrhythmia in 52.6% patients and ventricular fibrillation in 38.4%. There was no significant difference in terms of P and R wave amplitudes, pacing thresholds, and lead impedance at implantation and follow-up in the two groups. There was similarly no difference in terms of defibrillation thresholds (DFT) at implantation. Patients in group 1 had an average DFT of 10.2 +/- 5.2 J compared to 10.3 +/- 4.1 J in Group 2, P = NS. This study demonstrates no significant advantage of a dual coil lead system over a single coil system in terms of lead values and defibrillation thresholds. This may have important bearing on the choice of lead systems when implanting ICDs.

The purpose of this study was to evaluate the efficacy, safety, and clinical benefit of radiofrequency catheter ablation (RFCA) in a large series of patients with atrial tachycardia (AT). The determinants of success or failure of RFCA in AT remain unclear. We evaluated the results of radiofrequency ablation in 73 women and 32 men (mean age 48 +/- 19 years) with AT. Mapping techniques were based on identification of the earliest endocardial atrial electrogram recorded during AT. AT originated from the right atrium in 91 patients and from the left atrium in 14. The cardiac ventricles were dilated in 12 patients. AT ablation was successful in 80 patients (77%) regardless of the site of origin. Age, gender, rate of tachycardia, temperature achieved during application, or presence of tachycardiomyopathy were not significant determinants of acute success by univariate analysis. There was a significantly higher acute success rate of ablation in patients with paroxysmal (88%, 45 of 51) and permanent (71%, 30 of 42) forms than in patients with repetitive forms of AT (41%, 5 of 12) (p

In patients with sustained ventricular tachyarrhythmias and myocardial ischemia due to multivessel coronary artery disease, it remains unclear whether revascularization is enough to control the arrhythmias or whether additional implantation of a defibrillator is indicated. We therefore reviewed our clinical strategy of performing both bypass surgery and implantation of a defibrillator in patients with syncopal ventricular tachycardia or fibrillation and significant multivessel coronary artery disease. We retrospectively reviewed the outcome of 18 patients with malignant ventricular tachyarrhythmias, significant multivessel coronary artery disease, and signs of myocardial ischemia who underwent both bypass surgery and defibrillator implantation. Data on these patients were compared to data from 232 other defibrillator patients with respect to baseline clinical variables, cardiac events, and mortality during follow-up. Except for underlying pathology, no other important differences in baseline characteristics were noted between the study patients and the other defibrillator patients. The cumulative occurrence of shocks during follow-up was comparable in both groups (66% vs 67%). The cumulative survival from all-cause mortality was 94% in the study patients and 78% in the others (P = NS). Pre- and postoperative electrophysiological testing was not useful to predict arrhythmia recurrences. In this population of patients with ventricular tachyarrhythmias and ischemia due to multivessel coronary artery disease, bypass surgery alone would not have prevented recurrences of arrhythmias. An excellent survival and a high incidence of shocks after both bypass surgery and defibrillator implantation were observed.

The ICD can effectively recognize and treat ventricular arrhythmias that can lead to sudden death. Sudden death is a major problem in patients awaiting heart transplantation. We reviewed our experience with the ICD in patients with malignant ventricular arrhythmias waiting for cardiac transplantation. Nineteen patients were included. Seventeen were men, mean age was 54 +/- 11 years (range 17-66) and the left ventricular ejection fraction was 22% +/- 10% (range 9%-46%). After a mean follow-up of 6 +/- 5 months (range 1-20 months), 17 patients reached heart transplantation. One patient died and the other is waiting for a transplant. Before transplantation 71% of patients received an appropriate discharge. The mean time to the first appropriate discharge was 2 +/- 2 months (range < 1-6 months), which was significantly shorter than the mean time to first discharge in the other patients (n = 182) receiving a defibrillator in our center (11 +/- 10 months; range 1-58 months) (P < 0.0004). In conclusion, cardiac transplantation candidates with life-threatening ventricular arrhythmias can effectively be protected against sudden arrhythmic death by ICD. These patients have a high incidence of appropriate shocks occurring very early after implantation.

Objectives. We report the occurrence of cardiac events during long-term follow-up in patients with hypertrophic cardiomyopathy (HCM) after cardioverter-defibrillator implantation.Background. The identification of patients at high risk for sudden death and the prevention of recurrence of sudden death in HCM represents a difficult problem.Methods. We retrospectively analyzed the occurrence of cardiac events during follow-up of 13 patients with HCM who received an implantable cardioverter-defibrillator (ICD) because of aborted sudden death (n = 10) or sustained ventricular tachycardia (n = 3) (group I). Findings were compared with those in 215 patients with an ICD and other structural heart disease or idiopathic ventricular fibrillation (group II).Results. After a mean (±SD) follow-up period of 26 ± 18 months, 2 of 13 patients in group I received appropriate shocks. The calculated cumulative incidence of shocks was 21% in group I and 66% in group II after 40 months (p < 0.05). We observed a low incidence of recurrence of ventricular tachycardia/fibrillation during follow-up in patients with HCM. No deaths occurred.Conclusions. Our data suggest that ventricular tachyarrhythmias may not always be the primary mechanism of syncope and sudden death in patients with HCM. The ICD seems to have a less important impact on prognosis in patients with HCM than in patients with other etiologies of aborted sudden death.

A prospective invasive hemodynamic evaluation in 11 unselected patients with medically refractory chronic atrial fibrillation undergoing radiofrequency catheter ablation of the atrioventricular junction was performed. The resultant rate regulation and control caused a hemodynamic and symptomatic improvement despite persistent fibrillation at the atrial level.

Two hundred thirty-five patients underwent RF catheter ablation of AV conduction for symptomatic drug refractory AF (84%), atrial flutter (9%), and atrial tachycardia (7%). In the first 100 patients, postablation pacing was not prospectively set at any specific rate and was always < or = 70 beats/min. In the next 135 patients, postablation pacing was prospectively set at 90 beats/min for 1-3 months. Six of the first 100 patients (6%) had VF or sudden death after the RF procedure and none (0%) of the next 135 patients did (P < 0.05). One of the six patients had recurrent VF 4 days after the ablation. Five patients were successfully resuscitated and one patient died. There were no statistically significant differences between patients with and without (aborted) sudden death or between the first 100 and the next 135 patients with respect to age, sex, underlying heart disease, EF, number of RF applications, or left-or right-sided approach of the procedure. VF mostly occurred during episodes of slow ventricular escape rhythms or during slow ventricular pacing. We conclude that malignant ventricular arrhythmias and sudden death are possible complications of RF ablation of the AV function. The mechanism of these complications could have a bradycardia dependent nature and it seems that the occurrence of malignant arrhythmias can be prevented by temporarily pacing the heart at relatively fast rates immediately after ablation.

Although the beneficial effects of DDD pacing are well known, currently available ICDs provide only fixed rate ventricular antibradycardia pacing. In a consecutive series of 139 patients with ICDs, we have analyzed the need for antibradycardia pacing and the indications for DDD pacing. We also report our initial experience with the Defender 9001 (ELA Medical, France) DDD-ICD. Out of 139 patients, 25 (18%) were in need of antibradycardia pacing. Ten patients already had a pacemaker at the time of ICD implantation and ten other patients had a conventional pacemaker indication at that time. Five patients became pacemaker dependent during a follow-up of 20 +/- 8 months. The disorders necessitating pacemaker therapy were high degree AV conduction disturbances in 72%, sick sinus syndrome in 12%, and AF with a slow ventricular response in 16% of patients. Based upon current indications, DDD pacing was indicated in 20 (80%) of 25 patients. The Defender 9001 DDD-ICD (ELA Medical) was used in two patients with ischemic cardiomyopathy and pacemaker syndrome with VVI pacing. Cardiac output during DDD pacing increased by 36% in one patient with an increase in VO2 max during exercise of 29%. The other patient showed an increase in cardiac output of 50% with DDD pacing, and, while unable to exercise with VVI pacing, had a VO2max of 24 mL/kg per minute during DDD pacing. Up to 18% of our ICD patients are in need of antibradycardia pacing. Of these pacemaker dependent patients, 80% have an indication for DDD pacing. Our first clinical experience with a DDD-ICD confirms the hemodynamic benefit of AV synchronous pacing in ICD patients with pacemaker syndrome.

Placing a pacing lead for left ventricular pacing through the coronary sinus can be hampered by anatomic obstacles. In this case report we describe a technique that can overcome the problem of sharply angulated coronary sinus branches by using simultaneously two guidewires in the target vessel.

Objective To evaluate the feasibility and results of isolated endoscopic pulmonary vein isolation for paroxysmal atrial fibrillation using robotics. Methods Between November 2004 and December 2005, 13 patients (38.5% female) underwent robotic pulmonary vein isolation at our institution. Mean age was 46.8 ± 8.4 years and mean preoperative duration of atrial fibrillation was 52.7 ±31.5 months. Indication for surgery was symptomatic drug-refractory paroxysmal atrial fibrillation or recurrence after percutaneous treatment (n = 3). Mean preoperative left atrial dimension was 38.5 ± 6.9 mm. The surgical procedure was performed off-pump as an isolated right chest approach. All procedures were performed using the Flex 10 microwave ablator (Guidant, Indianapolis, IN), which was positioned from the right side through the transverse sinus and around the 4 pulmonary veins. Postoperative drug regimen included sotalol and Coumadin. Mean follow-up was 8.5 ± 3.4 months. Results The procedure was successful in 11 patients. One patient needed conversion to median sternotomy for right pulmonary artery bleeding and a second patient had severe transverse sinus adhesions requiring conversion to a bilateral video-assisted small thoracotomy approach. No other morbidity occurred. Mean procedure time in successful cases was 2.7 ± 0.8 hours (range 1.7 to 4 hours). Permanent sinus rhythm was successfully restored in 10 of 13 patients (76.9% beyond 6 months). Nonsuccessful patients had markedly reduced symptoms and frequency of events. One patient required a left and another a right atrial flutter ablation during follow-up. Conclusions Robotic pulmonary vein isolation is a feasible procedure that has the potential to become a valid option in the treatment of paroxysmal atrial fibrillation.

Posteroseptal accessory pathways are sometimes resistant to ablation because of the complex anatomy of this region. Ex-vivo experiments have demonstrated that gold-tip radiofrequency ablation catheters create deeper lesions than conventional platinum-iridium tip catheters. This case of a 62-year-old man with Wolf-Parkinson-White syndrome illustrates that the ability to create such lesions can be a very useful option when previous attempts with platinum-iridium tip catheters have failed.

This survey assesses the current management strategies for individuals with electrocardiographic features, suggesting an arrhythmogenic syndrome [including long QT syndrome (LQTS), Brugada syndrome (BS), catecholaminergic polymorphic ventricular tachycardia (CPVT) or short QT syndrome] or family members of patients with a known arrhythmogenic syndrome, in 44 large European centres. The principal findings of this survey were: (i) the number of new patients with arrhythmogenic syndromes (symptomatic and asymptomatic) is relatively small; (ii) the clinical work-up of these patients consists mainly of non-invasive tests; (iii) a relatively high use of genetic testing is noted, especially in LQTS and CPVT; (iv) EP testing is commonly performed in asymptomatic BS patients and in family members of symptomatic BS patients; and (v) the majority of European electrophysiologists focus on first-degree relatives when dealing with family members of an index patient.

Background —Several cases of unexpected death have been reported with sildenafil in patients predisposed to ischemic cardiac events. Although acute episodes of ischemia could account for some of these deaths, we hypothesized that sildenafil may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia. Methods and Results —Studies were undertaken in 10 isolated guinea pig hearts that demonstrated prolongation of cardiac repolarization in a reverse use-dependent manner by sildenafil 30 μmol/L. Action potential duration increased 15% from baseline 117±3 to 134±2 ms with sildenafil during pacing at 250 ms cycle length, whereas a 6% increase from 99±2 to 105±2 ms was seen with pacing at 150 ms cycle length. Experiments in human ether-a-go-go –related gene (HERG)–transfected HEK293 cells (n=30) demonstrated concentration-dependent block of the rapid component (I Kr ) of the delayed rectifier potassium current: activating current was 50% decreased at 100 μmol/L. This effect was confirmed using HERG-transfected Chinese hamster ovary (CHO) cells, which exhibit no endogenous I K -like current. Conclusions —Sildenafil possesses direct cardiac electrophysiological effects similar to class III antiarrhythmic drugs. These effects are observed at concentrations that may be found in conditions of impaired drug elimination such as renal or hepatic insufficiency, during coadministration of another CYP3A substrate/inhibitor, or after drug overdose and offer a new potential explanation for sudden death during sildenafil treatment.

We studied whether functional improvement after cardiac resynchronization therapy (CRT) is associated with reversal of the heart failure (HF) gene program.Cardiac resynchronization therapy improves exercise tolerance and survival in patients with advanced congestive HF and dyssynchrony.Twenty-four patients referred for CRT underwent left ventricular (LV) endomyocardial biopsies immediately before CRT implantation (baseline). In addition, 17 of them underwent LV endomyocardial biopsy procurement 4 months later (follow-up). In 6 control patients with normal LV function, LV biopsies were obtained at the time of coronary artery bypass grafting. The LV messenger ribonucleic acid (mRNA) levels of contractile and calcium regulatory genes were measured by quantitative real time polymerase chain reaction and normalized for glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The HF patients showing an improvement in New York Heart Association (NYHA) functional class by1 score and a relative increase in LV ejection fractionor =25% at 4 months after CRT were considered as responders.The HF patients were characterized by lower LV mRNA levels of alpha-myosin heavy chain (alpha-MHC), beta-myosin heavy chain (beta-MHC), sarcoplasmic reticulum calcium ATPase 2alpha (SERCA), phospholamban (PLN), and higher brain natriuretic peptide (BNP) mRNA levels as compared with control subjects. Responders to CRT (n = 11) showed an increase in LVEF (p0.001), a decrease in left ventricular end-diastolic diameter (p = 0.003), and NYHA functional class (p = 0.002), and a reduction in N-terminal proBNP levels (p = 0.032) as compared with baseline. This was associated with an increase in mRNA levels of alpha-MHC (p = 0.035), SERCA (p = 0.032), a decrease in BNP mRNA levels (p = 0.002), and an increase in the ratio of alpha-/beta-MHC (p = 0.018) and SERCA/PLN (p = 0.012). No significant changes in molecular profile were observed in nonresponders.In HF patients with electromechanical cardiac dyssynchrony, functional improvement related to CRT is associated with favorable changes in established molecular markers of HF, including genes that regulate contractile function and pathologic hypertrophy.

Aims To analyse the follow-up data of implantable cardioverter-defibrillator (ICD) therapy in Brugada syndrome (BS). Methods and results We conducted a retrospective, single centre study of 47 patients (mean age: 44.5 +/- 15 years) with BS, who underwent primary prophylactic ICD implantation. All patients had baseline spontaneous (23 patients) or drug-induced (24 patients) coved type I ECG pattern. All patients were judged to be at high risk because of syncope (26 patients) and/or a positive family history of sudden death (26 patients). During a median follow-up of 47.5 months, seven patients had appropriate shocks. The presence of spontaneous type I ECG and non-sustained ventricular tachyarrhythmia in the ICD datalog suggested a trend towards shorter appropriate shock-free survival by Kaplan-Meier analysis (P = 0.037 and P = 0.012, respectively). Seventeen patients received inappropriate shocks (IS); eight patients for sinus tachycardia; six patients for new onset atrial arrhythmias; and five patients for noise oversensing. In multivariable Cox-regression analysis, new onset atrial fibrillation (AF) and less than 50 years of age were independent predictors of significantly shorter IS-free survival (P = 0.04 and P = 0.036, respectively). Conclusion In high-risk patients with BS, primary prophylactic ICD therapy is an effective treatment. In this, young and otherwise healthy patient population, the IS rate is high.