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Aims Prevalent atrial fibrillation (AF) is associated with excess cardiovascular (CV) death (D) and hospitalizations (H) in heart failure (HF) with preserved ejection fraction (pEF). We evaluated if it had an independent role in excess CVD in HFpEF and studied its impact on cause-specific mortality and HF morbidity. Methods and results We used propensity score–matched (PSM) cohorts from the TOPCAT Americas trial to account for confounding by other co-morbidities. Two prevalent AF presentations at study entry were compared: (i) subjects with Any AF event by history or on electrocardiogram (ECG) with PSM subjects without an AF event and (ii) subjects in AF on ECG with PSM subjects in sinus rhythm. We analyzed cause-specific modes of death and HF morbidity during a mean follow-up period of 2.9 years. A total of 584 subjects with Any AF event and 418 subjects in AF on ECG were matched. Any AF was associated with increased CVH [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11–1.61, P = 0.003], HFH (HR 1.44, 95% CI 1.12–1.86, P = 0.004), pump failure death (PFD) (HR 1.95, 95% CI 1.05–3.62, P = 0.035), and HF progression from New York Heart Association (NYHA) classes I/II to III/IV (HR 1.30, 95% CI 1.04–1.62, P = 0.02). Atrial fibrillation on ECG was associated with increased risk of CVD (HR 1.46, 95% CI 1.02–2.09, P = 0.039), PFD (HR 2.21, 95% CI 1.11–4.40, P = 0.024), and CVH and HFH (HR 1.37, 95% CI 1.09–1.72, P = 0.006 and HR 1.65, 95% CI 1.22–2.23, P = 0.001, respectively). Atrial fibrillation was not associated with risk of sudden death. Both Any AF and AF on ECG cohorts were associated with PFD in NYHA class III/IV HF. Conclusion Prevalent AF can be an independent risk factor for adverse CV outcomes by its selective association with worsening HF, HFH, and PFD in HFpEF. Prevalent AF was not associated with excess sudden death risk in HFpEF. Atrial fibrillation was also associated with HF progression in early symptomatic HFpEF and PFD in advanced HFpEF. Trial registration TOPCAT trial is registered at www.clinicaltrials.gov:identifier NCT00094302.

Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. The aim of this review was to evaluate the progress made in the management of AF over the two last decades.Clinical classification of AF is usually based on the presence of symptoms, the duration of AF episodes and their possible recurrence over time, although incidental diagnosis is not uncommon. The majority of patients with AF have associated cardiovascular diseases and more recently the recognition of modifiable risk factors both cardiovascular and non-cardiovascular which should be considered in its management. Among AF-related complications, stroke and transient ischaemic accidents (TIAs) carry considerable morbidity and mortality risk. The use of implantable devices such as pacemakers and defibrillators, wearable garments and subcutaneous cardiac monitors with recording capabilities has enabled to access the burden of "subclinical AF". The recent introduction of non-vitamin K antagonists has led to improve the prevention of stroke and peripheral embolism. Agents capable of reversing non-vitamin K antagonists have also become available in case of clinically relevant major bleeding. Transcatheter closure of left atrial appendage represents an option for patients unable to take oral anticoagulation. When treating patients with AF, clinicians need to select the most suitable strategy, i.e. control of heart rate and/or restoration and maintenance of sinus rhythm. The studies comparing these two strategies have not shown differences in terms of mortality. If an AF episode is poorly tolerated from a haemodynamic standpoint, electrical cardioversion is indicated. Otherwise, restoration of sinus rhythm can be obtained using intravenous pharmacological cardioversion and oral class I or class III antiarrhythmic is used to prevent recurrences. During the last two decades after its introduction in daily practice, catheter ablation has gained considerable escalation in popularity. Progress has also been made in AF associated with heart failure with reduced or preserved ejection fraction.Significant progress has been made within the past 2 decades both in the pharmacological and non-pharmacological managements of this cardiac arrhythmia.

Symptomatic atrial fibrillation (AF) or clinical AF is associated with impaired quality of life, higher risk of stroke, heart failure, and increased mortality. Current clinical classification of AF is based on the duration of AF episodes and the recurrence over time. Appropriate management strategy should follow guidelines of Scientific Societies. The last decades have been marked by the advances in mechanism comprehension, better management of symptomatic AF, particularly regarding stroke prevention with the use of direct oral anticoagulants and a wider use of AF catheter or surgical ablations. The advent of new tools for detection of asymptomatic AF including continuous monitoring with implanted electronic devices and the use of implantable cardiac monitors and recently wearable devices or garments have identified what is called "subclinical AF" encompassing atrial high-rate episodes (AHREs). New concepts such as "AF burden" have resulted in new management challenges. Oral anticoagulation has proven to reduce substantially stroke risk in patients with symptomatic clinical AF but carries the risk of bleeding. Management of detected asymptomatic atrial arrhythmias and their relation to clinical AF and stroke risk is currently under evaluation. Based on a review of recent literature, the validity of current clinical classification has been reassessed and appropriate updates are proposed. Current evidence supporting the inclusion of subclinical AF within current clinical classification is discussed as well as the need for controlled trials which may provide responses to current therapeutic challenges particularly regarding the subsets of asymptomatic AF patients that might benefit from oral anticoagulation.

Heart failure (HF) emergence in atrial fibrillation (AF) patients undergoing different treatment strategies has not been studied.AFFIRM trial subjects with no history of HF, without clinical HF and normal left ventricular ejection fraction at enrollment were identified. The principal outcome was time to development of a composite of New York Heart Association class ≥II HF and/or cardiovascular (CV) death. It was compared for rate and rhythm strategies and correlated with electrocardiographic parameters on follow-up (FU).A total of 1,771 patients (880 rate, 891 rhythm) were evaluated. The principal outcome occurred in 21.4% of rate and 16.8% of rhythm subjects at 5 years (hazard ratio [HR] 1.32, 95% CI 1.04-1.69, P = .024). HF increment by 2 classes increased total mortality (HR 2.83, 95% CI 1.91-4.18, P .0001), cardiac mortality, (HR 4.27, 95% CI 2.03-9.04, P = .0001), and CV hospitalizations (HR 3.04, 95% CI 2.15-4.29, P .0001). HF emergence during FU was associated with AF (P = .0004), ventricular rate80 beats/min (P = .0106), and higher frequency of recorded AF in the rhythm arm (25%-75% vs25%, HR 1.69, 95% CI 1.09-2.64, P = .020;75% vs25%, HR 3.15, 95% CI 1.87-5.34, P =.001).(1) In AF patients without HF, symptomatic HF emergence was more frequent with rate control than with rhythm control. (2) HF appearance presages increased mortality risk. (3) Delaying HF emergence is associated with effective rhythm control with documented sinus rhythm during75% of FU visits as well as ventricular rate control.

Introduction: USA and European guidelines recognize that an oral antiarrhythmic drug (AAD) for acute conversion of symptomatic atrial fibrillation (AF) can be effective in AF termination, provided a drug with rapid effect is used and safety precautions are followed. How the ‘pill in the pocket’ (PIP) approach is used in physicians’ practices has not been examined. We performed a survey to understand clinicians’ AAD PIP prescription practices in the USA and Europe. Methods: An online physician survey of 629 cardiologists and interventional electrophysiologists (EPs) was conducted in the USA, Germany, Italy, Sweden, and the UK. Respondents were treating ≥10 AF patients who received AAD therapy and/or had received or were referred for ablation. This exploratory survey contained 96 questions on physician demographics, AF types, and drug treatment practices. Results: Respondents in the USA and Europe, reported PIP use in 24% and 19% of their patients, respectively. Frequency of PIP use was greatest in paroxysmal AF without structural heart disease (SHD; 41%) vs paroxysmal AF with SHD (16%). In contrast to guideline recommendations, PIP was used in persistent AF (pers-AF) in 18% without SHD and in 12% with SHD. Use for pers-AF was highest in the USA and by EPs. For AF without SHD, class IC AADs were used most often (flecainide, 77%; propafenone, 32%), but there was notable use of amiodarone (Amio) (13%) and sotalol (Sot) (13%), the latter more in the USA and by EPs. For AF with SHD, class IC use diminished considerably. PIP was given with a rate control agent (new or chronically, beta blocker > calcium channel blocker) in 71%, while 29% gave PIP AADs without concomitant rate control agents. Optimal arrhythmia frequencies for PIP were felt to be: monthly (13%), q2-3 months (46%), q4-6 months (26%), q7-12 months (11%), and yearly or less (4%), with no notable differences between the USA and Europe, or cardiologists and EPs. Conclusions: Our survey revealed that clinicians in both the USA and Europe use PIP in almost a quarter of their patients, mostly for AF with minimal or no heart disease (guideline appropriate). However, Amio and Sot use for PIP and use of PIP for pers-AF was evident, highlighting the need for further interventions on the appropriate and optimal use of the PIP strategy.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Electrophysiology Research Foundation Introduction Atrial fibrillation (AF) is known to impact cardiovascular(CV) mortality in heart failure (HF) patients (pts) with preserved ejection fraction (pEF) but its exact causes are unknown. Methods We analyzed demographic, clinical, ECG and AF presentation as predictors of CV mortality, sudden death( SCD) and pump failure death(PFD) in HFpEF pts in the TOPCAT AMERICAS trial. We analyzed two AF presentations 1. Pts in sinus rhythm (SR, n = 1319) compared to AF on ECG (n = 446) at entry or 2. Pts with no AF event by history or ECG ( n = 1007 ) to those with any AF event (n = 760 ). Results (Table): 5 year (yr) CV mortality was higher in pts with AF on ECG (30%) than SR (18%, p = 0.014) but 5 yr SCD was (10% in AF on ECG & 7% in any AF) & comparable to SR (7% & 9% respectively, p = ns). 5 yr PFD was higher in AF on ECG (13%) than SR (5%, p = 0.007) Conclusions : 1. CV death risk in HFpEF pts increased with AF on ECG.. 2. SCD was not more frequent with both AF presentations 3. PFD in HFpEF increased with age, ECG recorded AF & elevated heart rate. 4. The recording of AF on ECG was more strongly associated with CV death & PFD, possibly due to greater AF burden . Predictors of adverse outcomes in HFpEF AF on ECG* Any AF* Endpoint Covariate HR (95% CI) p-value HR (95% CI) p-value Time to cardiovascular death Atrial Fibrillation* 1.44 (1.08, 1.92) 0.014 1.15 (0.87, 1.51) 0.338 Age (years) 1.03 (1.02, 1.05)

Aims: We studied the impact of atrial fibrillation (AF) presentation on total & cause-specific cardiovascular (CV) mortality & hospitalizations (H) in mild & advanced heart failure (HF) strata as well as HF worsening in the TOPCAT AMERICAS study.Methods: We analyzed 1765 subjects with HF & preserved ejection fraction (pEF) and AF with two AF different presentations at entry: a) Any AF event (remote or ongoing, n=760), to those without any such AF events (n=1005) and b) Ongoing AF on ECG at enrollment (n=446), to those in sinus rhythm (SR, n=1319). Results; During a mean follow-up of 2.9 years, CV mortality was higher in subjects with AF on ECG (30% vs. 18% at year 5, hazard ratio (HR) of 1.44, 95% CI 1.08-1.92, p=0.014) with an disproportionate increase in pump failure deaths {PFD} (HR 2.04, 95% CI 1.22-3.42, p=0.007) but not sudden death {SCD} (HR 1.17, 95% CI 0.69-1.96, p=0.563). HF worsening was more frequent with Any AF (HR 1.31, 95% CI 1.09-1.58, p=0.005). Increased risk of PFD was seen with Any AF ( p= 0.001) & AF on ECG (p=0.002) in the advanced HF class stratum without enhancing SCD risk (p>0.7 for both). Conclusions: Both AF presentations increased risk of PFDs, but not SCD. Ongoing AF worsened CV mortality in HFpEF by disproportionately increasing PFDs and Any AF promoted HF worsening. Adverse CV outcomes with AF in HFpEF are caused by excess PFDs and/ or by HF worsening varying by AF presentation & HF stratum.

Introduction: Presence of atrial fibrillation (AF) is known to increase mortality and impact cardiovascular(CV) outcomes in heart failure (HF) patients (pts) with preserved systolic function (pEF) but its causes are unknown Hypothesis: We hypothesized that AF presentation & clinical factors impact mode of death & CV outcomes of HFpEF pts in the TOPCAT AMERICAS trial. Methods: We analyzed demographic, clinical, ECG and AF presentation as predictors of CV mortality, sudden death( SCD) and pump failure death(PFD). We examined two AF presentations 1. Pts in sinus rhythm (SR, n=1319) compared to pts in AF (n=446) on ECG at study entry or 2. Pts with no AF event by history or ECG ( n=1007 ) compared to those with any AF event (n=760 ) during a mean follow up period of 2.9 years(yrs). Results: AF pts when compared to the rest of the study population were more likely to be older, male, Caucasian origin, have more alcohol use, diabetes, percutaneous coronary interventions. 5 yr CV mortality was higher in pts with AF on ECG (30%) than those in sinus rhythm (18%, p=0.014) but 5 yr SCD was lower (10% in AF on ECG & 7% in any AF) & comparable to SR (7% & 9% respectively, p=ns). 5 yr PFD was higher (13%) than SR (5%, p=0.007. )Table shows Cox proportional hazards analysis of covariates associated with time to CV death, time to SCD & time to PFD adjusted for baseline imbalances. Conclusions:: 1. CV death risk in HFpEF pts increased with age, in minorities, smokers, diabetics, with lower systolic bp, elevated heart rate & AF on ECG.. 2. SCD was more frequent in males, African Americans & diabetics but was low in both AF & SR, perhaps due to a dominant atrial & limited ventricular arrhythmogenic substrate in HFpEF. 3. PFD in HFpEF increased with age, ECG recorded AF & elevated heart rate.This may reflect importance of atrioventricular synchrony in HFpEF. 4. The recording of AF on ECG at study entry was more strongly associated with CV death & PFD, possibly due to greater AF burden in this group compared to those with any AF even..

Objectives This study assessed the relationship between atrial fibrillation (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-randomization AF. Background AF is common in heart failure with preserved ejection fraction (HFpEF) and likely contributes to increased risk of adverse outcomes. Methods A total 1,765 patients enrolled in TOPCAT trial in North and South America were divided into 3 groups: no known AF, history of AF without AF at enrollment, and AF found on the electrocardiogram (ECG) at enrollment. We assessed outcomes and treatment response to spironolactone in all groups, and the association between post-randomization AF and outcomes in patients free of AF at baseline. The primary outcome of the TOPCAT trial was a composite of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Results A total of 760 patients (43%) had a history of AF (18%) or AF on ECG at enrollment (25%). The highest adjusted risk was associated with AF at enrollment (primary outcome, hazard ratio: 1.34; 95% confidence interval: 1.09 to 1.65; p = 0.006; and an increased early risk of secondary outcomes). Neither history of AF nor AF at enrollment modified the beneficial treatment effect of spironolactone. Post-randomization AF, which occurred in 6.3% of patients, was not influenced by spironolactone treatment, but was associated with an increased early risk of the primary outcome (hazard ratio: 2.32; 95% confidence interval: 1.59 to 3.40; p Conclusions AF at enrollment was associated with increased cardiovascular risk in HFpEF patients in the TOPCAT study. Post-randomization AF, which was associated with an increased risk of morbidity and mortality, was not influenced by spironolactone. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302).

Traditional right ventricular (RV) pacing for the management of bradyarrhythmias has been pursued successfully for decades, although there remains debate regarding optimal pacing site with respect to both hemodynamic and clinical outcomes. The deleterious effects of long-term RV apical pacing have been well recognized. This has generated interest in approaches providing more physiological stimulation, namely, His bundle pacing (HBP). This paper reviews the anatomy of the His bundle, early clinical observations, and current approaches to permanent HBP. By stimulating the His-Purkinje network, HBP engages electrical activation of both ventricles and may avoid marked dyssynchrony. Recent studies have also demonstrated the potential of HBP in patients with underlying left bundle branch block and cardiomyopathy. HBP holds promise as an attractive mode to achieve physiological pacing. Widespread adaptation of this technique is dependent on enhancements in technology, as well as further validation of efficacy in large randomized clinical trials.

Warfarin is deemed safe compared to bridging with heparin in the peri-procedure setting while implanting cardiac devices. The timing of discontinuation and re-initiation of direct anticoagulant agents (DOACs) such as dabigatran, apixaban, and rivaroxaban in the peri-procedural setting in comparison to warfarin is not well studied. We wanted to compare three DOAC agents with warfarin during cardiac device implantation. Consecutive patients on treatment with dabigatran, rivaroxaban, or apixaban (group A) undergoing a cardiac device generator change, upgrade, or new implantation procedure were compared to those on warfarin (group B). Incidence of hematoma, infection, effusion, stroke, and other complications were noted at 1 day, 1 week, and 3 months. A total of 311 patients in group A underwent the above procedures with 73 patients on dabigatran, 153 on rivaroxaban, and 85 on apixaban. There were 467 patients on warfarin in group B. Mean age of the total population was 68 ± 12 years with 67% males and > 80% Caucasians. The last dose of the DOAC was the night prior to the procedure and resumed the night of the procedure (single dose interruption for apixaban and dabigatran and no un-interruption for rivaroxaban). There was no difference noted in the incidence of minor or major hematoma (9% vs 8.5%, p = 0.7). No stroke occurred in either group. Use of DOAC agents with transient interruption of one dose is as safe as warfarin in the peri-procedural setting during implantation of cardiac devices.

Three-dimensional mapping and intracardiac echocardiography are important tools for the study of the site of origin of an arrhythmia and its substrate. This review examines the application of these techniques in the diagnosis and treatment of sinoatrial tachycardias with a special focus on the syndrome of inappropriate sinus tachycardia. The use of these techniques in electrophysiologic mapping and interventions such as catheter ablation is discussed. Three-dimensional mapping provides unique insights into the generation of normal and abnormal sinus impulses in man and their propagation in the atrium. It permits precise placement of ablation lesions and assessment of real-time electrophysiologic impact of these interventions. Intracardiac echocardiography provides delineation of important anatomic structures in the vicinity of the sinoatrial node complex and monitors the safety of interventions such as catheter ablation.

We examined the long-term (≥ 5 years) outcomes of dual-site atrial pacing (DAP) when added to background antiarrhythmic drugs (AADs) and/or ablation in patients with refractory atrial fibrillation (AF) and heart failure (HF). Seventy-three patients with HF (mean NYHA HF class of 2.5) and AF refractory to AADs and/or ablation were implanted with DAP systems to achieve biatrial electrical and mechanical resynchronization (ART) and rhythm control (RC). Thirty-eight patients with refractory AF and HF with preserved ejection fraction (HFpEF) and 35 with reduced ejection fraction (HFrEF) were enrolled. HFpEF patients had higher left ventricular ejection fraction compared to HFrEF (53 ± 5 vs. 31 ± 10% p

This study assessed the relationship between atrial fibrillation (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-randomization AF.AF is common in heart failure with preserved ejection fraction (HFpEF) and likely contributes to increased risk of adverse outcomes.A total 1,765 patients enrolled in TOPCAT trial in North and South America were divided into 3 groups: no known AF, history of AF without AF at enrollment, and AF found on the electrocardiogram (ECG) at enrollment. We assessed outcomes and treatment response to spironolactone in all groups, and the association between post-randomization AF and outcomes in patients free of AF at baseline. The primary outcome of the TOPCAT trial was a composite of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization.A total of 760 patients (43%) had a history of AF (18%) or AF on ECG at enrollment (25%). The highest adjusted risk was associated with AF at enrollment (primary outcome, hazard ratio: 1.34; 95% confidence interval: 1.09 to 1.65; p = 0.006; and an increased early risk of secondary outcomes). Neither history of AF nor AF at enrollment modified the beneficial treatment effect of spironolactone. Post-randomization AF, which occurred in 6.3% of patients, was not influenced by spironolactone treatment, but was associated with an increased early risk of the primary outcome (hazard ratio: 2.32; 95% confidence interval: 1.59 to 3.40; p 0.0001) and secondary outcomes.AF at enrollment was associated with increased cardiovascular risk in HFpEF patients in the TOPCAT study. Post-randomization AF, which was associated with an increased risk of morbidity and mortality, was not influenced by spironolactone. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302).

Implantable devices are now being routinely used for the treatment of patients with malignant ventricular tachyarrhythmias. This technology became an approved clinical therapy in the United States in 1985. The prototype implantable cardioverterdefibrillator ICD was developed in the 1970s and investigated in the 1980s. Since its approval in 1985 for general clinical application, ICDs are being increasingly used in patients with life-threatening ventricular tachyarrhythmias based upon a number of clinical trials undertaken in North America and western Europe.

Dual-site right atrial pacing (DAP) produces electrical atrial resynchronization but its long-term effect on the atrial mechanical function in patients with refractory atrial fibrillation (AF) has not been studied. Drug-refractory paroxysmal (PAF) and persistent AF (PRAF) patients previously implanted with a dual-site right atrial pacemaker (DAP) with minimal ventricular pacing modes (AAIR or DDDR mode with long AV delay) were studied. Echocardiographic structural (left atrial diameter [LAD] and left ventricular [LV] end diastolic diameter [EDD], end systolic diameter [ESD]) and functional (ejection fraction [EF]) parameters were serially assessed prior to, after medium-term (n = 39) and long-term (n = 34) exposure to DAP. During medium-term follow-up (n = 4.5 months), there was improvement in left atrial function. Mean peak A wave flow velocity increased with DAP as compared to baseline (75 ± 19 vs. 63 ± 23 cm/s, p = 0.003). The long-term impact of DAP was studied with baseline findings being compared with last follow-up data with a mean interval of 37 ± 25 (range 7–145) months. Mean LAD declined from 45 ± 5 mm at baseline to 42 ± 7 mm (p = 0.003). Mean LVEF was unchanged from 52 ± 9 % at baseline and 54 ± 6 % at last follow-up (p = 0.3). There was no significant change in LV dimensions with mean LVEDD being 51 ± 6 mm at baseline and 53 ± 5 mm at last follow-up (p = 0.3). Mean LVESD also remained unchanged from 35 ± 6 mm at baseline to 33 ± 6 mm at last follow-up (p = 0.47). During long-term follow-up, 30 patients (89 %) remained in sinus or atrial paced rhythm as assessed by device diagnostics at 3 years. DAP can achieve long-term atrial reverse remodeling and preserve LV systolic function. DAP when added to antiarrhythmic drug (AAD) and/or catheter ablation (ABL) maintains long-term rhythm control and prevents AF progression in elderly refractory AF patients. Reverse remodeling with DAP may contribute to long-term rhythm control.

Objectives The impact of individual antiarrhythmic drugs (AADs) on mortality and hospital stay in atrial fibrillation (AF) was evaluated. Background Cardiovascular (CV) outcomes in AF patients receiving pharmacologic rhythm control therapy have not been compared with rate control therapy on the basis of AAD selection. Methods We compared CV outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) trial in subgroups defined by the initial AAD selected with propensity score matched subgroups from the rate arm (Rate). Results Seven hundred twenty-nine amiodarone patients, 606 sotalol patients, and 268 Class 1C patients were matched. The composite outcome of mortality or cardiovascular hospital stays (CVH) showed better outcomes with Rate compared with amiodarone (hazard ratio [HR]: 1.18, 95% confidence interval [CI]: 1.03 to 1.36, p = 0.02), sotalol (HR: 1.32, 95% CI: 1.13 to 1.54, p Conclusions In AFFIRM, composite mortality and CVH outcomes differed for Rate and AADs due to differences in CVH; CVH event rates during follow-up were high for all cohorts, but they were higher for all groups on AADs. Death, intensive care unit hospital stay, and non-CV death were more frequent with amiodarone. (Atrial Fibrillation Follow-Up Investigation of Rhythm Management; NCT00000556)

The temporal patterns of onset of persistent atrial fibrillation (AF) recurrences leading to established persistent AF is currently unknown. Three hundred thirty patients with a history of paroxysmal AF and bradycardia (mean age, 70 ± 10 years; 61% male) with implanted pacemakers that automatically recorded the cumulative daily atrial tachyarrhythmia (AT) burden were included in the analysis. Persistent AF was defined as device data showing ≥7 consecutive days with ≥23 h of AT. We analyzed the pattern and duration of persistent AF recurrences and time to each persistent AF episode recurrence. Seventy-eight patients (24%) developed their first persistent AT/AF after 147 ± 149 days. Follow up ranged from 14 to 499 days. Median AF burden in the week prior to persistent AF was 3.5 h/day. Fifty-four patients (16%) had a minimum of 180 days follow up after initial detection of persistent AF. Three of 54 patients (6%) immediately developed established AF; 32 of 51 patients (63%) returned to sinus rhythm but then had a second persistent AF event. These 32 patients had a minimum of 90 days follow up and 25 of these 32 patients (78 %) had a third persistent AF event. Time to recurrence analysis showed progressive abbreviation in persistent AF onset. The median durations of the first, second, and third persistent AF events were 16, 13, and 17 days, respectively. (1) The time to first, second, and third persistent AF recurrences progressively decreases with a high likelihood of established persistent AF within 9 months of onset. (2) These data support intermittent but frequent AF monitoring for the detection of persistent AF recurrences to assess the efficacy of rhythm control interventions.

The Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) study is a single-blinded, parallel randomized designed multicenter study in pacemaker indicated patients with paroxysmal atrial fibrillation (AF). The objective is to evaluate whether the site of atrial pacing--conventional right atrial appendage versus low atrial septal--with or without atrial overdrive pacing will influence the development of persistent AF. The study will provide a definitive answer to whether a different atrial pacing site or the use of AF suppression pacing or both can give incremental antiarrhythmic benefit when one is implanting a device for a patient with a history of paroxysmal AF.

Background: We undertook a pilot investigation to evaluate the feasibility of a novel technique using intracardiac echocardiography (ICE) for intraoperative assessment of cardiac resynchronization therapy (CRT). Methods: We evaluated ICE intraoperative imaging of left ventricular (LV) function and aortic valvular flow as well as safety of implementation. ICE was used to guide CRT system lead placement, assess impact of pacing modes, and optimization of device programming. Results: Twenty-three patients underwent ICE imaging. ICE showed global hypokinesis in six patients, regional wall motion abnormality only in 10 patients, and both in seven patients. Optimized CRT modes included mean atrioventricular (AV) interval of 170 ms and interventricular timing using simultaneous right ventricular (RV)-LV pacing (five patients), LV pacing only (one patient), and sequential LV to RV stimulation (15 patients) or RV to LV stimulation (two patients). ICE-guided CRT acutely improved mean left ventricular ejection fraction (LVEF) from 24 ± 9% to 41 ± 1% (P < 0.00001). During follow-up of 3–24 (mean 11) months, New York Heart Association class improved in all patients from a mean of 3.2 ± 0.4 at implant to 1.6 ± 0.7 (P < 0.0001), with improvement of LVEF from 19 ± 7% to 34 ± 12% (P = 0.0001). Actuarial survival was 83% at 12 months. Conclusions:(1) ICE imaging is reliable and safe for continuous intraoperative imaging of LV wall motion, and assesses baseline status and impact of CRT interventions.(2) Intraoperative ICE-guided CRT optimization resulted in an increase in LVEF acutely and consistent improvement in heart failure.(3) Sequential biventricular pacing and longer AV interval programming were more often used in ICE-guided CRT.

Implantable cardioverter defibrillator (ICD) trials were initially limited to survivors of sudden death. The focus of defibrillator trials in the last decade has been in prophylactic implantation of the device in high risk populations for the prevention of sudden cardiac death. It is the contention in this review that the new focus for implantable defibrillator trials in 2008 and beyond will be on more selective and focused use of this therapy. This could be achieved by selecting ICD patients based on their pathophysiologic and genetic risk. Increasing effort will also be placed on using the device for prevention of spontaneous malignant ventricular tachyarrhythmias and the index clinical sudden death event. Finally, implantable defibrillators will be used in combination in a "hybrid" therapy approach. ICDs will be increasingly combined either with ventricular tachycardia ablation or ventricular fibrillation ablation using catheter techniques. With the addition of cardiac resynchronization therapy in these devices, new clinical trials that use cardiac resynchronization therapy as an early intervention in specific high risk heart failure populations and refinement of the CRT technique to improved optimal results are in progress. Finally, combining ICD devices and regenerative medicine approaches to myocardial replacement therapy are being explored.

The experimental concept that "atrial fibrillation (AF) begets AF" implies that atrial tachyarrhythmia (AT)/AF burden uniformly increases over time. However, the temporal patterns of paroxysmal AT/AF burden progression, its conversion to persistent AF, and the relationship to underlying disease in humans are unknown. We analyzed the average daily AT/AF burden in patients with concomitant bradycardia and paroxysmal AF to examine these issues.Three hundred thirty patients with a history of paroxysmal AF (mean age 70 +/- 10 years; 61% male) were implanted with a pacemaker that automatically recorded the cumulative daily AT/AF burden. Persistent AT/AF was defined as 7 consecutive days with23 hours of AT on the device data logs. Antiarrhythmic drug therapy was required to be stable for at least 7 months.Average follow-up was 401 +/- 123 days. Seventy-eight patients (24%) progressed to persistent AT/AF during the follow-up period with a mean interval of 147 +/- 149 days. Mean AT/AF burden increased progressively (slope 14 s/d, P.001) over 500 days after implant, and median AT/AF burden also increased (P.01) in this subgroup of patients. This increase was highly correlated with the presence of structural heart disease (P.001). There was a concomitant decrease in atrial premature beat (APB) frequency. Most patients transitioning to persistent AF were in sinus rhythm with minimal AT/AF burden in the days immediately before persistent AF. Neither mean nor median AT/AF burden increased over time in patients remaining in paroxysmal AF (slope 0 s/d, P = .7) despite a higher APB frequency than in patients with heart disease (P =.003) and a higher likelihood of daily AT/AF events (P.001).Temporal patterns of AT/AF burden in patients developing persistent AF show a progressive increase with a sudden transition to persistent AF. This is more consistent with substrate changes, rather than increased density of triggering APBs or paroxysmal AT/AF events. Thus, progression to persistent AF is probably related to an AF substrate, which is undergoing progressive structural remodeling owing to heart disease and other factors and is now suddenly capable of sustaining prolonged or multiple ATs. Therapies directed at the atrial substrate may be needed to prevent persistent AF.

Heart rhythm disorders are a major global public health challenge. This review highlights worldwide inequalities, access to care issues, early experiences with pilot projects, and promotion of global access to modern heart rhythm therapy.

The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have recently published, in both the Journal of the American College of Cardiology (JACC) and Circulation, a Scientific Statement on the Evaluation of Syncope ('Statement'). This Scientific Statement was commissioned to provide guidance for clinicians regarding the evaluation of patients who present with 'syncope'. The Statement was not intended to be a formal set of practice guidelines. However, in the absence of generally accepted practice guidelines in North America, the Statement's potential impact on clinical care may be more far-reaching than expected; it may erroneously be considered to be the authoritative 'de-facto' guideline document. This commentary, submitted by a multidisciplinary consortium of more than 60 physicians with expertise in the management of transient loss of consciousness (TLOC), points out that in many respects the ACCF/AHA Syncope Statement fails to address long-standing clinical errors associated with the evaluation of episodes of apparent TLOC, including syncope. If not appropriately revised, the current Statement may lead to both inadequate patient care as well as a potentially damaging legal environment for physicians undertaking evaluation of patients who present with transient loss of consciousness.

Introduction: Stable organized atrial tachyarrhythmias (ATs) /"rotors" that maintain AF have been identified in patients (pts) with paroxysmal atrial fibrillation (PAF) & persistent AF (PRAF) with no or minimal heart disease. Hypothesis: Biatrial ATs occur in AF pts with systolic heart failure (HF). Methods: We performed simultaneous contact catheter mapping of the RA & LA using 3 D non-contact mapping ) in 83 refractory AF pts during spontaneous AF episodes.Spontaneous atrial premature beats (APBs) & triggered ATs were analyzed. We also compared regional distribution of ATs & activation patterns in pts with & without HF. Results: 24 HF pts, mean age of 62±9 years, 75% male with mean left ventricular ejection fraction (LVEF) 45.5±9% and mean left atrial (LA) size 4.35±0.8 cm were mapped. They had 42 APBs that triggered 26 distinct organized stable ATs/"rotors". Each pt had 1 to 4 RA or LA regions showing triggering APBs (mean 1.75/pt) initiating AT. APBs arose predominantly from the RA or LA septum (45%) & superior LA/PV (24%) regions (Fig 1a). A biatrial distribution of the stable ATs/"rotors" occcurred in HF pts (Fig 1b) with few focal ATs. Compared to pts without HF (n=59), HF pts (n=24) trended to have more PRAF (83% vs 66%, p=0.18). 78 organized stable ATs/"rotors" were compared for regional distribution in PRAF pts with HF (n=16) & without HF (n=32). Stable ATs with focal LA/PV origin were uncommon in both groups (7% vs. 15%). LA ATs/"rotors" were similar (26% vs. 17%; p=0.58) as were typical RA flutter and atypical RA ATs/"rotors" in both groups (Fig 1c). Conclusions: 1. A majority of APBs initiating AF in HF pts originated from the septal and superior LA/PV regions. 2. While triggers are still frequently present with the LA/PV origin in HF pts, stable ATs/"rotors" had biatrial distribution & a lesser frequency of focal LA/PV ATs. 3. This spectrum of ATs/"rotors" was similar to PRAF pts without HF, potentially supporting similar ablative interventions in both pt groups.

Hybrid therapy strategies have combined antiarrhythmic drugs (AAD) with pacemakers, atrio-ventricular defibrillators (AV ICD) or atrial ablation individually. The feasibility combining AAD with dual site RA pacing (DAP) in an AV ICD has not been examined.We used an AV ICD with a novel lead configuration permitting DAP, antitachycardia pacing (ATP) or atrial shocks (ADF) in patients (pts) with refractory persistent or permanent AF. Hybrid therapy included linear RA ablation and/or focal ablation. Continuous DAP and automatic ATP with patient or physician activated ADF.24 pts, mean age 66 +/- 10 yrs, with cardiac disease (22 pts), underwent insertion of an AVICD with dual RA leads. 20 patients had concomitant ablative procedures (RA only = 19, RA + LA = 1) and all pts continued previously ineffective AAD. During a follow-up of 2-36 months (mean 17 +/- 8 mos), rhythm control was restored in all ptsmaintained long-term in 19 (83%) pts. 8 pts used AF termination therapies successfully. Device datalogs showed no episodes of AF in 6 pts, asymptomatic brief arrhythmias in 4 pts, infrequent paroxysmal AF in 9 ptspersistent AF recurred in 5 pts. AV ICD detection algorithms reliably detected AF or AT in the DAP mode in all pts. Intermittent brief P wave double counting occurred during AT in selected pts. No pt received inappropriate ADF therapy.1. DAP can be safely incorporated in an AVICD devices for use in an hybrid therapy strategy for AF pts. 2. These devices can be effective for both AF preventiontermination. 3. Long term rhythm control can be achieved and documented by device datalogs in persistent and permanent AF.

The ICE CHIP study is a sequential Phase I and Phase II pilot study comparing the cardiac imaging capabilities of intracardiac echocardiography (ICE) with with transesophageal echocardiography (TEE) followed by a randomized comparison of ICE guided cardioversion with a conventional cardioversion strategy in patients with atrial fibrillation. It is a prospective open label randomized multi-center investigation performed in two phases designed to initially compare two distinct imaging modalities (Phase 1) and subsequently two different strategies (ICE guided Cardioversion and Conventional) in the management of AF in patients undergoing invasive cardiac procedures in whom electrical cardioversion is indicated (Phase 2). This study will examines two hypotheses in AF patients undergoing invasive cardiac procedures: (1) ICE has comparable efficacy to TEE in visualization of left atrial pathology including thrombi or interatrial septal defects. This will be evaluated during the Phase I component of the study. (2) ICE can identify low risk patients in whom immediate cardioversion during the procedure is safe and comparably effective to electrical cardioversion performed based on a conventional strategy of a minimum of 3 weeks of preceding anticoagulation therapy. Phase 1 will enroll 100 patients at 12 centers, who will undergo a clinically indicated TEE procedure and cardiac catheterization procedure. Each patient will be imaged by TEE & ICE and a core echo laboratory will perform a blinded comparison of the two imaging modalities. In Phase 2, a total of 300 patients (3:2 randomization) will be enrolled in the study at up to 15 investigational sites in USA and Europe. The composite incidence rate of major cardiac and bleeding complications (stroke, TIA, peripheral embolism, major hemorrhagic event) will be compared between the two treatment groups over the duration of the study.

Mapping of Atrial Fibrillation. Introduction: While atrial fibrillation (AF) initiation in the pulmonary veins has been well-studied, simultaneous biatrial and three-dimensional noncontact mapping (NCM) has not been performed. We hypothesized that these two techniques would provide novel information on triggers, initiation, and evolution of spontaneous AF and permit study of different AF populations. Methods and Results: The origin of atrial premature beats (APBs), onset of spontaneous AF and its evolution were analyzed in 50 patients with AF in the presence or absence of structural heart disease (SHD) and in different AF presentations (group A: Persistent, group B: Paroxysmal). In 45 patients, spontaneous APBs in the right atrium (RA; n = 60) and left atrium (LA; n = 25) with similar regional distributions regardless of heart disease status were demonstrated. In total, 22 patients (44%) had >2 disparate regional origins. Biatrial regional foci were seen with equal frequency in patients with SHD (31%), without SHD (40%), in group A (32%), and in group B (36%). Biatrial mapping and NCM showed organized monomorphic atrial tachyarrhythmias arising in the RA (17), septum (17), or LA (21) and were classified as atrial flutter (RA = 34, LA = 8), macro-reentrant atrial tachycardia (RA = 1, LA = 3) or focal atrial tachycardia (RA = 2, LA = 7). Their regional distribution was more extensive in patients with SHD and persistent AF compared with patients without SHD or paroxysmal AF. Simultaneous biatrial tachycardias were observed only in group A patients and those with SHD. Conclusions: Simultaneous biatrial and NCM permits successful AF mapping in different AF populations and demonstrates a biatrial spectrum of spontaneous triggers and tachycardias. Organized monomorphic tachycardias with multiple unilateral or biatrial locations are commonly observed in human AF. Patients with heart disease or persistent AF have a more extensive distribution as well as simultaneous coexistence of multiple tachycardias during AF.

Objectives The purpose of this study was to correlate patient-reported symptoms of atrial fibrillation with the underlying rhythm. Background The reliability of patient-reported symptoms as a marker of atrial fibrillation recurrence has not been well studied. Methods This prospective multicenter trial correlated the recurrence of atrial tachyarrhythmias with symptoms in patients with a history of atrial fibrillation and a standard indication for permanent pacing. Pacemaker-detected atrial tachyarrhythmia events were correlated with symptoms. Patients logged symptomatic events into the device's memory via an external manual activator. Patients were followed for 12 months and were contacted weekly to ensure compliance with activator usage. Episodes were classified as symptomatic atrial tachyarrhythmia, asymptomatic atrial tachyarrhythmia, or symptomatic nonatrial tachyarrhythmia depending on concordance between patient symptoms and the rhythm. Results Forty-eight patients underwent implantation of a DDDRP pacemaker and were followed for 12 ± 2 months. A median of 25.0 (4.0–55.8) symptomatic events attributed to atrial fibrillation. A median of 1.0 (0.0–10.0) symptomatic atrial tachyarrhythmia episodes were documented during follow-up. Symptoms related to atrial fibrillation were reported in 6% of atrial tachyarrhythmia episodes identified by the pacemaker. The probability that symptoms were associated with an atrial tachyarrhythmia (positive predictive value) was 17%. The ventricular rate between symptomatic and asymptomatic atrial tachyarrhythmia events was not significantly different. Conclusions Among patients with symptomatic bradycardia and a history of atrial fibrillation, symptoms of atrial fibrillation often were not associated with documented atrial tachyarrhythmias, and more than 90% of atrial tachyarrhythmias were clinically silent.

We evaluated the long-term efficacy, safety, and applicability of a "hybrid" therapy strategy for rhythm control in atrial fibrillation (AF), incorporating dual-site right atrial pacing, antiarrhythmic drugs, and right atrial ablation. One hundred thirteen patients (paroxysmal AF [n = 70], persistent/permanent AF [n = 43]) with refractory symptomatic AF were treated with this strategy and followed for 1 to 81 months (mean 30 +/- 23). All-cause mortality, AF recurrences, and progression to permanent AF were monitored and recorded by implanted device data logs. There was no procedural mortality. Rhythm control was achieved in 90% of all patients at 3 and 5 years, with comparable efficacy in subpopulations with paroxysmal (98%), persistent, or permanent AF (87%, p >2). Overall survival was 84% at 3 years and 80% at 5 years, and was higher in patients with paroxysmal AF than in patients with persistent or permanent AF (86% vs 67% at 4 years, p

PURPOSE OF REVIEW Present generation implantable cardioverter-defibrillators (ICD) have become a proven primary therapeutic option in management of symptomatic ventricular arrhythmias and are now being increasingly used for primary prevention. The addition of biventricular pacing and atrial defibrillation to these devices has had an impact on the management of several new patient populations. The widespread application of these devices requires precise knowledge of their potential benefits and factors that could adversely affect device function. RECENT FINDINGS ICD therapy has improved the survival of coronary disease patients with left ventricular dysfunction by reducing sudden death rate. In congestive heart failure patients, ICD therapy and biventricular pacing improves heart failure status thus improving overall survival and quality of life. Atrial defibrillation can establish rhythm control in drug refractory atrial fibrillation usually in a "hybrid therapy" prescription. SUMMARY Implantable cardioverter defibrillators have proven to be invaluable in the primary and secondary prevention of sudden cardiac death. Incorporation of new technology in these devices has resulted in expanded indications that improve survival and quality of life of new patient populations.