New-generation atrial antitachycardia pacing (Reactive ATP) is associated with reduced risk of persistent or permanent atrial fibrillation in patients with bradycardia: Results from the MINERVA randomized multicenter international trial.

BACKGROUND: Atrial fibrillation (AF) is a frequent comorbidity in patients with pacemaker and is a recognized cause of mortality, morbidity, and quality-of-life impairment. The international MINimizE Right Ventricular pacing to prevent Atrial fibrillation and heart failure trial established that atrial preventive pacing and atrial antitachycardia pacing (DDDRP) in combination with managed ventricular pacing (MVP) reduce permanent AF occurrence in comparison with standard dual-chamber pacing (DDDR). OBJECTIVE: We aimed to determine the role of new-generation atrial antitachycardia pacing (Reactive ATP) in preventing AF disease progression. METHODS: Patients with dual-chamber pacemaker and with previous atrial tachyarrhythmias were randomly assigned to DDDR (n = 385 (33%)), MVP (n = 398 (34%)), or DDDRP+MVP (n = 383 (33%)) group. The incidence of permanent AF, as defined by the study investigator, or persistent AF, defined as ≥7 consecutive days with AF, was estimated using the Kaplan-Meier method, while its association with patients' characteristics was evaluated via multivariable Cox regression. RESULTS: At 2 years, the incidence of permanent or persistent AF was 26% (95% confidence interval [CI] 22%-31%) in the DDDR group, 25% (95% CI 21%-30%) in the MVP group, and 15% (95% CI 12%-20%) in the DDDRP+MVP group (P < .001 vs. DDDR; P = .002 vs. MVP). Generalized estimating equation-adjusted Reactive ATP efficacy was 44.4% (95% CI 41.3%-47.6%). Multivariate modeling identified high Reactive ATP efficacy (>44.4%) as a significant predictor of reduced permanent or persistent AF risk (hazard ratio 0.32; 95% CI 0.13-0.781; P = .012) and episodes' characteristics, such as long atrial arrhythmia cycle length, regularity, and the number of rhythm transitions, as predictors of high ATP efficacy. CONCLUSION: In patients with bradycardia, DDDRP+MVP delays AF disease progression, with Reactive ATP efficacy being an independent predictor of permanent or persistent AF reduction.

Improving thromboprophylaxis using atrial fibrillation diagnostic capabilities in implantable cardioverter-defibrillators: the multicentre Italian ANGELS of AF Project.

BACKGROUND: Atrial fibrillation (AF) is a well-established risk factor for stroke and thromboembolism and is a frequent comorbid arrhythmia in patients with implantable cardioverter-defibrillators (ICDs). The Anticoagulation Use Evaluation and Life Threatening Events Sentinels (ANGELS) of AF project was a medical care program aimed at supporting adherence to oral anticoagulation (OAC) guidelines for thromboprophylaxis through the use of ICD AF diagnostics. METHODS AND RESULTS: Fifty Italian cardiology clinics followed 3438 patients with ICDs. In a subgroup of 15 centers (the ANGELS of AF centers), cardiologists attending to follow-up visits were supplied with specific reports describing stroke risk factors and risk scores (American College of Chest Physicians and CHADS(2) [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack]), AF occurrence and duration, and current antithrombotic therapy for patients with AF, especially those with a CHADS(2) score >0 and not on OAC therapy. The remaining centers represented a control group of patients as a comparison of OAC use. In the ANGELS of AF centers, 709 (36%) patients had AF described either in their clinical history (n=426 [22%]) or as new-onset AF (n=257 [14%]). Among 683 (96%) patients with CHADS2 score >0, 209 (30.6%) were not taking an OAC. Appropriate OAC therapy was prescribed in 10% (22/209) of patients after evaluation of ANGELS of AF reports. The percentage of patients on OAC therapy, as indicated by guidelines, increased during follow-up from 46.1% at baseline, to 69.4% at the stroke risk evaluation phase, to up to 72.6% at the end of the observation period. In control centers, corresponding figures were 46.9% at baseline and 56.8% at the end of the observation period (P<0.001 versus ANGELS of AF group). CONCLUSIONS: The ANGELS of AF project demonstrates the possibility to improve OAC use in accordance with available guidelines for stroke risk reduction in AF by supplying attending physicians with reports about patients risk factors and AF information from continuous ICD monitoring.

Cardiac resynchronization therapy in patients undergoing open-chest cardiac surgery.

PURPOSE: Few data are available on the effects of cardiac resynchronization therapy (CRT) in candidates for cardiac surgery and affected by severe heart failure (HF). The aim of our analysis is to evaluate the percentage of patients who maintain indication for CRT after surgery and the efficacy of CRT in those patients subsequently implanted. METHODS: We enrolled 124 HF patients with indication both to heart surgery and to CRT. During surgery, an epicardial left ventricular lead was implanted, tunneled to a subclavear pocket, and capped. Afterward, patients were periodically reassessed to confirm indication for CRT. RESULTS: CRT indication was confirmed within 1 month from surgery in 54 patients (group A) and in 33 patients within 6 months (group B). In group A and B, 63% and 71% of patients were considered responders according to an arbitrary five-point increase of left ventricular ejection fraction (LVEF), respectively. The assessment of clinical response at 1 year, based on the definitions proposed by Packer, identified 63% and 80% of responders in group A and B, respectively. CONCLUSIONS: Our data show that a remarkable percentage of patients maintain an indication for CRT after cardiac surgery (76%), while in the remaining 24% the lack of an indication is confirmed by a higher LVEF at last follow-up. In combination with surgery, CRT proved to be an effective therapy in those patients who were subsequently implanted. The suggested method is simple, without significant adjunctive risks, and allows easier CRT implantation with stable thresholds.

Intrathoracic and ventricular impedances are associated with changes in ventricular volume in patients receiving defibrillators for CRT.

BACKGROUND: Some implantable cardioverter defibrillators (ICD) are able to monitor intrathoracic impedance to detect pulmonary fluid overload. This is achieved by measuring impedance between the ICD case and the right ventricular (RV) lead. We hypothesized that the measured impedance would rise with improvement in left ventricular (LV) volumes during cardiac resynchronization therapy (CRT), and that such impedance changes would be more apparent when measured with an alternative pacing vector. METHODS: We analyzed echocardiographic and impedance data from heart failure patients implanted with a CRT-ICD capable of intrathoracic impedance measurement for fluid accumulation diagnosis, and LV pacing impedance recording for lead integrity monitoring. RESULTS: In 127 out of 170 patients that received de novo CRT implantation, the LV end-systolic volume (LVESV) decreased at 6-month follow-up (LVESV at 6 month-LVESV at baseline <0: group A). For the remaining 43 patients (group B) the change was > or = 0. Despite comparable values at baseline (P = 0.262), the impedances of groups A and B gradually diverged soon after the implant, resulting in significant difference between the two groups at the 6-month visit (P = 0.001). The changes in LV dimensions produced larger differences between groups in the impedance measured between the LV and the RV leads (P < 0.001). The regression analysis demonstrated an inverse correlation between paired changes of volume and intrathoracic impedance. Higher correlation coefficient was obtained using the LV-to-RV measurement vector (r =-0.635, P < 0.001). CONCLUSIONS: The changes in ICD-measured impedance seem associated with the LV volume changes induced by CRT. Specifically, the LV-to-RV impedance estimations seem to better correlate with paired changes of ventricular volumes.

Presence and duration of atrial fibrillation detected by continuous monitoring: crucial implications for the risk of thromboembolic events.

INTRODUCTION: Asymptomatic atrial fibrillation (AF) can expose patients to the risk of stroke. The primary objective of this study was to assess the incidence of thromboembolic events in relationship with CHADS(2) (congestive heart failure, hypertension, age >or=75 years, diabetes mellitus, and prior stroke, or transient ischemic attack) score and AF presence/duration. The secondary objective was to compare intermittent versus continuous monitoring strategies. METHODS AND RESULTS: Data from patients with an implanted pacemaker and a history of AF were analyzed. Thromboembolic risk was quantified through CHADS(2) score. Three AF groups were considered: patients with <5-minutes AF on 1 day (AF-free); patients with >5-minutes AF on 1 day but <24 hours (AF-5 minutes); patients with AF episodes >24 hours (AF-24 hours). Monitoring strategies involving 24-hour Holter, 1-week Holter, and 30-day Holter were simulated. Data from 568 patients continuously monitored for 1 year were analyzed: 171 (30%) had CHADS(2) score = 0; 269 (47%) had CHADS(2) score = 1; 111 (20%) had CHADS(2) score = 2; and 17 (3%) had CHADS(2) score >or= 3. During follow-up, 14 patients (2.5%) had an ischemic thromboembolic event. AF-24 hours patients numbered 223 (39.2%); AF-5 minutes, 179 (31.5%); and AF-free, 29.2%. By combining AF presence/duration with CHADS(2) score, two subpopulations with markedly different risks of events (0.8% vs 5%, P = 0.035) were identified, the former corresponding to AF-free with CHADS(2)5 minutes was 44.4%, 50.4%, and 65.1% for 24-hour Holter, 1-week Holter, and 1-month Holter monitoring, respectively. CONCLUSION: In patients with recurrent AF episodes, risk stratification for thromboembolic events can be improved by combining CHADS(2) score with AF presence/duration.

The Drug And Pace Health cliNical Evaluation (DAPHNE) study: a randomized trial comparing sotalol versus beta-blockers to treat symptomatic atrial fibrillation in patients with brady-tachycardia syndrome implanted with an antitachycardia pacemaker.

BACKGROUND: Atrial tachyarrhythmias (ATAs) are mainly treated by pharmacologic therapy for rate control or rhythm control. The aim of our study was to compare sotalol (S) versus beta-blocking agents (BB) in terms of prevention of ATA, cardioversions (CVs), and cardiovascular hospitalizations (H) in patients paced for bradycardia-tachycardia form of sinus node disease (BT-SND). METHODS: One hundred thirty-five patients (67 males, aged 73 +/- 7 years) were enrolled in a prospective, parallel, randomized, single-blind, multicenter study. All patients received a dual chamber rate adaptive pacemaker; after 1 month, 66 patients were randomly assigned to BB (62 +/- 26 and 104 +/- 47 mg/d for atenolol and metoprolol, respectively) and 69 patients to S (167 +/- 66 mg/d). RESULTS: After an observation period of 12 months, the percentage of patients free from ATA recurrences was 29% in both BB and S group. Cardioversion and H were significantly (P < .01) fewer in the 12 months after implantation than in the 12 months before both in patients treated with S (CV 69.4% vs 22.2%, H 91.7% vs 33.3%) and in patients treated with BB (CV 58.5% vs 17.1%, H 82.9% vs 26.8%). Kaplan-Meier survival analysis showed a nonsignificant trend toward a lower incidence of the composite end point (CV + H) among BB patients. CONCLUSIONS: In the complex context of "hybrid therapy" in patients with BT-SND implanted with a modern dual chamber rate adaptive pacemaker device delivering atrial antitachycardia pacing, no differences were found between the use of beta-blocker and the use of S, at the relatively low dose achieved after clinical titration, in terms of prevention of cardiovascular H or need for atrial CV.

Rate control in patients with pacemaker affected by brady-tachy form of sick sinus syndrome.

BACKGROUND: In sinus node disease (SND) atrial tachyarrhythmias (ATs) may frequently occur, after implant of a pacemaker for bradycardia, and are to be managed by rate or rhythm control. METHODS: We evaluated ventricular heart rate (HR) during AT, AT-related symptoms and hospitalizations in 333 patients who received DDDRP pacemakers for SND. RESULTS: In days with 24 hours of AT, mean daily HR during AT was > 80, 90, 100, 110, and 120 beats per minute (bpm) in 191 (57%), 114 (34%), 55 (16%), 23 (7%), and 11 (3%) patients, respectively. The proportion of patients with a mean daily HR > 80 bpm during AT despite the use of rate control agents was 28% among patients treated with calcium-channel blockers, 43% with digoxin, 49% with a combination of agents, 54% with amiodarone, 64% with sotalol, and 69% with beta blockers. Patients with HR > 100 bpm experienced a higher prevalence of both AT-related hospitalizations and cardiovascular hospitalizations than those with HR < or = 100 bpm (36% vs 21%, P = .013; 42% vs 28%, P = .003) and a significantly higher number of AT-related symptoms (1.8 +/- 0.9 vs 1.4 +/- 1.0, P = .008). CONCLUSIONS: Limited attention has been dedicated to rate control in patients with pacemaker. This is the first study to evaluate the prevalence and implications of inappropriate rate control in patients with pacemaker. We found that in a substantial proportion of patients with SND who have recurrent ATs despite pacing, mean daily HR during AT is high and that these patients present increased hospitalizations and more symptoms, thus suggesting the need to improve rate control.

Temporal variability of atrial fibrillation in pacemaker recipients for bradycardia: implications for crossover designed trials, study sample size, and identification of responder patients by means of arrhythmia burden.

BACKGROUND: Most clinical trials that have tested pacing therapies to prevent and treat atrial tachyarrhythmias (AT) have chosen endpoints such as AT frequency or burden (defined as percentage of time a patient is in AT), but failed to show unequivocal evidence of a clinical impact. AIM: The aim of our multicenter prospective observational study was to measure the variability of AT burden and estimate its impact on study outcomes. METHODS AND RESULTS: Two hundred and fifty patients indicated for permanent pacing and suffering from AT (age 71 +/- 9 years; 47.2% male) received a dual-chamber pacemaker. AT burden was measured in two consecutive, 2-month observation periods; the Monte Carlo method was then applied to simulate findings of a crossover design study. We simulated several models of therapy impact, each model being characterized by the percentage of responder patients and the percentage reduction in AT burden. To show a significant impact of AT therapies in a sample of 250 patients in whom 100, 75, or 50% would be theoretical responders to therapies, AT burden reduction should be at least 27, 32, or 57%, respectively. Temporal fluctuations in AT burden were so high that about 60% of patients would falsely appear as responders or nonresponders in a crossover study, regardless of AT burden reduction. CONCLUSIONS: In patients paced for bradycardia and suffering from AT, high intrapatient variability in AT burden was measured. Various models of therapy impact showed that, in crossover trials of AT therapies, time-related fluctuations in AT burden negatively impact on sample sizes and impair the ability to identify patients as responders or nonresponders.

Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers.

OBJECTIVES: The aim of our study was to evaluate arterial embolism (AE) occurrence rates and predictors in patients suffering from bradycardia and wearing a pacemaker with antitachycardia pacing therapies. BACKGROUND: Atrial fibrillation (AF) is associated with a high incidence of AE. METHODS: A total of 725 patients (360 men, age 71 +/- 11 years) were implanted with a DDDRP pacemaker (Medtronic AT500, Medtronic Inc., Minneapolis, Minnesota). At baseline 225 (31.0%) patients received antiplatelet therapy and 264 (36.4%) patients received anticoagulation agents. RESULTS: Over a median 22-month follow-up (25th to 75th interquartile range 16 to 30 months), AE occurred in 14 (1.9%) patients: 7 patients suffered a nonfatal ischemic stroke (0.6% per year), 4 patients had transient ischemic attack (0.34% per year), and 3 patients had embolic complications. Among baseline patients' characteristics, multivariate logistic analysis showed that embolic events are independently associated to ischemic heart disease (7.0 odds ratio [OR], 95% confidence interval [CI] 2.3 to 21.3, p = 0.001), prior embolic event (7.3 OR, 95% CI 1.2 to 43.9, p = 0.029), diabetes (5.0 OR, 95% CI 1.2 to 15.7, p = 0.032), and hypertension (4.1 OR, 95% CI 1.1 to 15.6, p = 0.036). The risk of embolism, adjusted for known risk factors, was 3.1 times increased (95% CI 1.1 to 10.5, p = 0.044) in patients with device-detected atrial fibrillation episodes longer than one day during follow-up. CONCLUSIONS: In a cohort of patients with bradycardia and AF, arterial embolism was common in patients with ischemic cardiopathy, hypertension, diabetes mellitus, and in patients with known stroke risk factors. Atrial fibrillation occurrences longer than one day were independently associated with embolic events.

Predictors of atrial antitachycardia pacing efficacy in patients affected by brady-tachy form of sick sinus syndrome and implanted with a DDDRP device.

UNLABELLED: Predictors of ATP efficacy in brady/tachy patients. BACKGROUND: Recent options to treat atrial tachyarrhythmias (ATA) include implantable devices delivering antitachycardia pacing therapies (ATP). No prospective study selected patients with higher chances of episode termination by ATP or indicated the most effective ATP use. Our aim was to study ATP efficacy in patients with brady-tachy form of sinus node disease (SND), identifying clinical factors, ATA characteristics, and device features predicting ATP efficacy. METHODS AND RESULTS: Three hundred and sixteen patients (105 M, aged 71.1+/-8.8 years) received a DDDRP pacemaker and were prospectively followed. Median follow-up was 18 months: 37,125 ATA episodes occurred in 217 patients; ATP treated 5,536 of them. Overall, ATP efficacy was 50.0%. A multivariate analysis identified longer arrhythmia cycle lengths (OR=1.25; CI=1.07-1.47) and shorter delays to ATP delivery (OR=0.15; CI=0.10-0.22) as independent predictors of ATP efficacy for episodes preceded by >or=5 minutes of sinus rhythm. Additionally, ATP efficacy for all treated episodes was predicted by lower New York Heart Association (NYHA) class (OR=0.64; CI=0.42-0.98), episode classification as nonimmediate recurrence of ATA (non-IRAT) (OR=0.07; CI=0.02-0.33), absence of overlap in the device detection windows (OR=0.54; CI=0.32-0.91), and flecainide treatment (OR=2.22; CI=1.04-4.71). CONCLUSIONS: In patients paced for SND, multivariate analysis shows that ATP efficacy is associated to longer arrhythmia cycle lengths, shorter ATP delivery delays, NYHA class I, episode classification as non-IRAT, absence of overlap in the atrial arrhythmia device detection windows, and flecainide treatment.

Temporal variability of atrial tachyarrhythmia burden in bradycardia-tachycardia syndrome patients.

AIMS: Several studies have tested non-pharmacological therapies for atrial tachyarrhythmias (ATs) by measuring the cumulative time (burden) the patient spends in arrhythmia. Contradictory results questioned either therapy efficacy or statistical power of the trials. We studied AT burden variability in patients paced for sinus node disease (SND) in order to interpret currently published data appropriately and to evaluate reliable sample sizes. METHODS AND RESULTS: One hundred and five patients with AT and SND received a dual chamber pacemaker with antitachyarrhythmia-pacing capability, and were followed for 13 months. Seventy-eight patients (74%) suffered AT recurrences. Device-gathered diagnostic measures were used to simulate results of randomized studies both with crossover and parallel design. The sample size required for statistically significant results was calculated as a function of the expected therapy-induced burden reduction. AT burden intra-patient variability was high: 43% of patients showed intrinsic fluctuations hiding any therapy-induced burden reduction lower than 30%. Demonstrating therapeutic breakthrough through a 6 month study would require 290 patients with crossover design and 5800 patients with parallel design. Doubling the study period requires 400 and 3000 patients, respectively. CONCLUSION: Patients with AT and paced for SND showed high intra-patient burden variability, which could possibly hide an AT burden reduction induced by a therapy. Previous studies involving non-pharmacological therapies utilizing AT burden endpoints could lack the power to reach statistical significance.

Implantable loop recorders: a novel method to judge patient perception of atrial fibrillation. Preliminary results from a pilot study.

INTRODUCTION: At the present time, several techniques are used or are under investigation for atrial fibrillation (AF) therapy. Nowadays, no well-defined target for such therapies has been yet completely identified. Furthermore, AF is an arrhythmia with high rates of recurrences, both symptomatic and asymptotic. Thus the measure of therapy success rates not only based on symptom perception remains a goal to be reached. AIMS OF THE STUDY: This study investigates the role of an implantable loop recorder (ILR) as an additional tool to identify initiating and perpetuating mechanisms of AF. The role of right atrial linear ablation (RALA) procedures is also investigated using the monitoring capabilities of the ILR. METHODS AND RESULTS: Nine patients (mean age 63.8 +/- 5.9) with paroxysmal AF were referred to our institution as candidates for AF ablation. All patients (pts) had in their medical history several years of AF episodes. Therefore pts were aware of AF related symptoms. Six of them were implanted with an ILR before ablation and were monitored one month before and six months after the procedure. The ILRs stored 54 patient activated events (PAE) and 124 automatically activated events (AAE). 68% of PAEs and 67% of AAEs were classified as appropriate. Most common reasons for inappropriate detections were premature atrial or ventricular contractions among PAEs and undersensing among AAEs. The arrhythmia onset was properly identified in 4 pts (44%). The average AF recurrence rate was 10.8 +/- 3.5 ep/month before ablation and 5.0 +/- 1.8 ep/month after the procedure ( p = 0.042). CONCLUSION: The ILR may be a helpful tool in monitoring pts undergoing ablation. Dedicated AF detection characteristics could give additional value to the device. RALA appears as a feasible, safe and relatively effective first approach in AF therapy.