Patient report outcomes in cryoballoon ablation of atrial fibrillation during the COVID Era: Insights from the 1STOP project.

BACKGROUND: Pulmonary vein isolation by cryoablation (PVI-C) is a standard therapy for the treatment of patients with symptomatic atrial fibrillation (AF). AF symptoms are highly subjective; however, they are important outcomes for the patient. The aim is to describe the use and impact of a web-based App to collect AF-related symptoms in a population of patients who underwent PVI-C in seven Italian centers. METHODS: A patient App to collect AF-related symptoms and general health status was proposed to all patients who underwent an index PVI-C. Patients were divided into two groups according to the utilization of the App or the non-usage. RESULTS: Out of 865 patients, 353 (41%) subjects composed the App group, and 512 (59%) composed the No-App group. Baseline characteristics were comparable between the two cohorts except for age, sex, type of AF, and body mass index. During a mean follow-up of 7.9±13.8 months, AF recurrence was found in 57/865 (7%) subjects with an annual rate of 7.36% (95% CI:5.67-9.55%) in the No-App versus 10.99% (95% CI:9.67-12.48%) in the App group, p=0.007. In total, 14,458 diaries were sent by the 353 subjects in the App group and 77.1% reported a good health status and no symptoms. In only 518 diaries (3.6%), the patients reported a bad health status, and bad health status was an independent parameter of AF recurrence during follow-up. CONCLUSIONS: The use of a web App to record AF-related symptoms was feasible and effective. Additionally, a bad health status reporting in the App was associated with AF recurrence during follow-up.

Axillary vein access for antiarrhythmic cardiac device implantation: a literature review.

The current narrative review provides an update of available knowledge on venous access techniques for cardiac implantable electronic device implantation, with a focus on axillary vein puncture. Lower procedure-related and lead-related complications have been reported with extrathoracic vein puncture techniques compared with intrathoracic accesses. In particular, extrathoracic lead access through the axillary vein seems to be associated with lower complication incidence than subclavian vein puncture and higher success rate than cephalic vein cutdown. In literature, many techniques have been described for axillary vein access. The use of contrast venography-guided puncture has facilitated the diffusion of the axillary vein approach for device implantation. Venography may be particularly useful in specific demographic and clinical device implantation contexts. Ultrasound-guided or microwire-guided vascular access for lead positioning can be considered a valid alternative to venography, although current applications for axillary vein puncture need further evaluations.

Detection of concealed structural heart disease by imaging in patients with apparently idiopathic premature ventricular complexes: A review of current literature.

BACKGROUND: Premature ventricular complexes (PVCs) are the most common form of ventricular arrhythmia in the general population. While in most cases PVCs represent a primitive phenomenon with benign behavior, in a non-negligible proportion of subjects frequent PVCs may be epiphenomenon of underlying occult heart diseases, requiring special medical attention since they have been resulted linked to increased total and cardiac mortality. Nevertheless, PVCs themselves, when incessantly frequent, may be responsible for left ventricular dysfunction in otherwise normal heart. Aim of this narrative review is to update current knowledge on the general approach to patients with frequent PVCs on the basis of available data, with a special focus on the value of imaging. HYPOTHESIS: Routine diagnostic work-up not infrequently miss subtle concealed arrhythmic substrate, leading to erroneously refer to such arrhythmias as to "idiopathic". METHODS: Literature search of PVCs articles was conducted in PubMed and Scopus electronic database. RESULTS: Conflicting data arise from literature about the true clinical significance of idiopathic PVCs. There is growing body of data providing evidence that more advanced non-invasive imaging modalities, such as cardiac magnetic resonance, have an incremental diagnostic and prognostic value. On the other hand, in some cases the prognostic significance of isolated subtle myocardial structural abnormalities in patients with PVCs, still remains area of uncertainty. CONCLUSION: In selected subjects with PVCs and high-risk features for concealed arrhythmic substrate, traditional assessment to rule out the presence of heart disease, including surface ECG and transthoracic echocardiography, should be implemented with more advanced cardiovascular imaging modalities.

Remote monitoring of subcutaneous implantable cardioverter defibrillators.

BACKGROUND: Remote monitoring (RM) of implantable cardioverter defibrillators (ICD) has been shown to improve patient safety and reduce in-office visits. The subcutaneous ICD (S-ICD) is an effective alternative to transvenous ICD and has recently been endowed with the RM function. However, the RM communicator for S-ICD requires patient interaction to activate data transmission. We assessed patient compliance and acceptance. METHODS: Patients with S-ICD received the communicator and were followed up for 15 months. Weekly remote transmissions were programmed. Compliance with checks was measured as the number of checks performed by the patient divided by the number of automatic notifications by the communicator. A questionnaire on acceptance of the system was administered to patients. RESULTS: A total of 106 patients were analyzed. The proportion of weekly checks properly executed by the patients was 94% during the first 3 months and 93% from months 12 to 15. Of the checks performed, 93% were on the same day as the automatic notification. On a patient basis, compliance with weekly checks was > 85% (less than one check missed per month) in 88% of patients during the first 3 months and in 82% from months 12 to 15 (p = 0.615). No variables emerged as predictors of lower (≤ 85%) long-term compliance with weekly checks. During follow-up, 49 alerts were transmitted and the mean delay between the detected event and the patient transmission was 2 ± 2 days. The majority of patients found the system easy to use and felt confident about being remotely monitored. CONCLUSIONS: The level of patient compliance with remote checks is high with current technology for RM of S-ICD. The vast majority of data transmissions are consistently performed on a weekly basis on the day scheduled.

Pulmonary vein isolation cryoablation for patients with persistent and long-standing persistent atrial fibrillation: Clinical outcomes from the real-world multicenter observational project.

BACKGROUND: Pulmonary vein isolation (PVI) is a cornerstone ablation strategy in the management of patients with atrial fibrillation (AF). Consensus guidelines and statements recommend PVI during the index catheter ablation procedure in patients with paroxysmal and persistent AF. OBJECTIVE: The objective of this analysis was to evaluate patients with persistent and long-standing persistent AF who were treated with the cryoballoon ablation catheter by PVI technique. METHODS: Consecutive patients with drug-refractory symptomatic persistent and long-standing persistent AF who underwent cryoballoon catheter ablation by a PVI-only procedure were prospectively included in this single-arm multicenter evaluation. Data on procedural characteristics, safety, and long-term freedom from AF recurrence were analyzed. RESULTS: Four hundred eighty-six subjects (mean age 60.8 ± 9.3 years; 389 (80%) men; 434 (89.3%) with persistent AF; 52 (10.7%) with long-standing persistent AF; left atrial diameter 44.6 ± 6.2 mm) underwent cryoballoon ablation in 35 Italian centers. The mean procedure time (skin-to-skin) was 109.9 ± 52.9 minutes, and the mean fluoroscopy time was 29.6 ± 14.5 minutes. Periprocedural complications were observed in 21 subjects (4.3%), and the acute PVI success rate was 97.6% across all patients. Using a 90-day blanking period, the single procedure Kaplan-Meier estimates of AF event-free survival were 63.9% at 12 months and 51.5% at 18 months. CONCLUSION: In this multicenter evaluation of cryoballoon ablation, the PVI procedure was safe, effective, and efficient with regard to the treatment of patients with persistent and long-standing persistent AF. The reasonable mid-term success rates agree with current clinical studies that establish PVI as a cornerstone index ablation strategy.

Implantable cardioverter-defibrillator-computed respiratory disturbance index accurately identifies severe sleep apnea: The DASAP-HF study.

BACKGROUND: Sleep apnea (SA) is a relevant issue in the management of patients with heart failure for risk stratification and for implementing treatment strategies. OBJECTIVE: The purpose of this study was to evaluate in patients with implantable cardioverter-defibrillators (ICDs) the performance of the respiratory disturbance index (RDI) computed by the ApneaScan algorithm (Boston Scientific Inc., Natick, MA) as a discriminator of severe SA. METHODS: ICD-indicated patients with left ventricular ejection fraction ≤35% were enrolled. One month after implantation, patients underwent a polysomnographic study. We evaluated the accuracy of the RDI for the prediction of severe SA (apnea-hypopnea index [AHI] ≥30 episodes/h) and the agreement between RDI and AHI during the sleep study night. RESULTS: Two hundred sixty-five patients were enrolled to obtain the required sample of 173 patients with AHI and RDI data for analysis. The mean AHI was 21 ± 15 episodes/h and severe SA was diagnosed in 38 patients (22%), while the mean RDI was 33 ± 13 episodes/h. On the basis of the receiver operating characteristic curve analysis of RDI values, the area under the curve was 0.77 (95% confidence interval [CI] 0.70-0.83; P < .001). At an RDI value of 31 episodes/h, severe SA was detected with 87% (95% CI 72%-96%) sensitivity and 56% (95% CI 48%-66%) specificity. RDI closely correlated with AHI recorded during the same night (r = 0.74; 95% CI 0.57-0.84; P < .001), and the Bland-Altman agreement analysis revealed a bias of 11 episodes/h, with limits of agreement being -10 to 32 episodes/h. CONCLUSION: The RDI accurately identified severe SA and demonstrated good agreement with AHI. Therefore, it may serve as an efficient tool for screening patients at risk of SA.

The effects of gender on electrical therapies for the heart: procedural considerations, results and complications: A report from the XII Congress of the Italian Association on Arrhythmology and Cardiostimulation (AIAC).

Use of cardiac implantable devices and catheter ablation is steadily increasing in Western countries following the positive results of clinical trials. Despite the advances in scientific knowledge, tools development, and techniques improvement we still have some grey area in the field of electrical therapies for the heart. In particular, several reports highlighted differences both in medical behaviour and procedural outcomes between female and male candidates. Women are referred later for catheter ablation of supraventricular arrhythmias, especially atrial fibrillation, leading to suboptimal results. On the opposite females present greater response to cardiac resynchronization, while the benefit of implantable defibrillator in primary prevention seems to be less pronounced. Differences on aetiology, clinical profile, and development of myocardial scarring are the more plausible causes. This review will discuss all these aspects together with gender-related differences in terms of acute/late complications. We will also provide useful hints on plausible mechanisms and practical procedural aspects.

Economic impact of remote monitoring after implantable defibrillators implantation in heart failure patients: an analysis from the EFFECT study.

AIMS: Heart failure (HF) patients with implantable cardioverter-defibrillators (ICD) require admissions for disease management and out-patient visits for disease management and assessment of device performance. These admissions place a significant burden on the National Health Service. Remote monitoring (RM) is an effective alternative to frequent hospital visits. The EFFECT study was a multicentre observational investigation aiming to evaluate the clinical effectiveness of RM compared with in-office visits standard management (SM). The present analysis is an economic evaluation of the results of the EFFECT trial. METHODS AND RESULTS: The present analysis considered the direct consumption of healthcare resources over 12-month follow-up. Standard tariffs were applied to hospitalizations, in-office visits and remote device interrogations. Economic comparisons were also carried out by means of propensity score (PS) analysis to take into account the lack of randomization in the study design. The analysis involved 858 patients with ICD or CRT-D. Of these, 401 (47%) were followed up via an SM approach, while 457 (53%) were assigned to RM. The rate of hospitalizations was 0.27/year in the SM group and 0.16/year in the RM group (risk reduction =0.59; P = 0.0004). In the non-adjusted analysis, the annual cost for each patient was €817 in the SM group and €604 in the RM group (P = 0.014). Propensity score analysis, in which 292 RM patients were matched with 292 SM patients, confirmed the results of the non-adjusted analysis (€872 in the SM group vs. €757 in the RM group; P < 0.0001). CONCLUSION: There is a reduction in direct healthcare costs of RM for HF patients with ICDs, particularly CRT-D, compared with standard monitoring. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/Identifier, NCT01723865.

Unexpected challenging case of coronary sinus lead extraction.

An 84-year-old woman implanted with cardiac resynchronization therapy defibrillator underwent transvenous lead extraction 4 mo after the implant due to pocket infection. Atrial and right ventricular leads were easily extracted, while the attempt to remove the coronary sinus (CS) lead was unsuccessful. A few weeks later a new extraction procedure was performed in our center. A stepwise approach was used. Firstly, manual traction was unsuccessfully attempted, even with proper-sized locking stylet. Secondly, mechanical dilatation was used with a single inner sheath placed close to the CS ostium. Finally, a modified sub-selector sheath was successfully advanced over the electrode until it was free of the binding tissue. The post-extraction lead examination showed an unexpected fibrosis around the tip. No complications occurred during the postoperative course. Fibrous adhesions could be found in CS leads recently implanted requiring non-standard techniques for its transvenous extraction.

Health economic concerns on cardiac rhythm management devices longevity and how to overcome them.

The number of device implantations is in constant increase due to the ageing population, extended indications to implant for preventing sudden cardiac death and treating heart failure. An increase in the number of implants is directly related to a higher number of device replacements and that is one of the most important risk factors for device infection. Therefore, all the above mentioned factors contribute to an increase in the cost for health care system. Currently, several methods help to prolong device battery longevity and consequently reduce the costs, such as: a new battery, drug eluting leads, high impedance leads, algorithm to minimize unnecessary pacing, capture management and correct programming to avoid inappropriate and unnecessary shock in Implantable Cardioverter Defibrillators and Cardiac Resynchronization Therapy devices. Furthermore remote monitoring is very promising to reduce health system costs related to devices.

Left Ventricular Reverse Remodeling Elicited by a Quadripolar Lead: Results from the Multicenter Per4mer Study.

BACKGROUND: To understand the impact of a quadripolar left ventricular (LV) lead on reverse remodeling and phrenic nerve stimulation (PNS) in congestive heart failure patients treated by cardiac resynchronization therapy at 8-month follow-up (FU). METHODS: One hundred and fifty-eight patients received an LV Medtronic Performa lead (Medtronic Inc., Minneapolis, MN, USA) and were reevaluated at FU by echocardiography and measurement of electrical parameters. RESULTS: A targeted LV lead placement was achieved in 140 (89%) patients. Super responders and responders were 76 (50%) and 26 (18%), respectively, at FU; seven (4%) died and 13 (8%) were hospitalized for any cause. Nonischemic etiology was the only independent predictor of reverse remodeling. The configurations available only with the Performa leads reduced PNS occurrence at 8 V@0.4 ms from 43 (27%) to 14 (9%) of patients at implantation, and from 44 (28%) to 19 (12%) at last FU, compared to configurations available with bipolar leads. Patients with detectable PNS had >10/16 pacing configurations with a PNS safety margin >2 V both at implantation and at FU. During FU 16 (10%) patients had an adverse event possibly related to the lead or to modification of the underlying heart disease but 99% of these events were fixed by reprogramming of the pacing vector. CONCLUSIONS: Performa Lead enables an increased capability to achieve a targeted lead positioning in the broad clinical scenario of large- and small-volume implanting centers, with a relevant impact on the occurrence of reverse remodeling compared to literature data. The enhanced management of PNS resulted in a dislodgement rate of only 1%.

Remote monitoring improves outcome after ICD implantation: the clinical efficacy in the management of heart failure (EFFECT) study.

AIMS: Internet-based remote interrogation systems have been shown to reduce emergency department and in-office visits in patients with implantable cardioverter defibrillators (ICDs), resulting in increased efficiency for healthcare providers. Nonetheless, studies sized to demonstrate the impact of remote monitoring on patients' outcome have been lacking. METHODS AND RESULTS: The EFFECT study was a multicentre clinical trial aimed at measuring and comparing the outcome of ICD patients conventionally followed-up by means of in-clinic visits (Standard arm) or by remote monitoring (Remote arm) in the clinical practice of 25 Italian centres. From 2011 to 2013, 987 consecutive patients were enrolled and followed up for at least 12 months. The primary endpoint was the rate of death and cardiovascular hospitalizations. Remote monitoring was adopted by 499 patients. Patients in the Standard and Remote arms did not differ significantly in terms of baseline clinical characteristics, except for a more frequent use of ICD with cardiac resynchronization therapy (CRT-D) in the Remote arm (48 vs. 36%, P < 0.001). One-year rates of the primary combined endpoint were 0.27 events/year for patients in the Standard arm and were 0.15 events/year for those in the Remote arm (incident rate ratio, 0.55; 95% CI, 0.41-0.73; P < 0.001). The endpoint rates in the Standard and Remote arms were 0.27 and 0.08 events/year, respectively, among CRT-D recipients (P < 0.001), and 0.28 vs. 0.21 among ICD patients (P = 0.094). The rates of in-office visits were 1.9 per year in the Standard arm and 1.7 per year in the Remote arm. CONCLUSION: Compared with the standard follow-up through in-office visits, remote monitoring is associated with reduced death and cardiovascular hospitalizations in patients with ICD in clinical practice. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/ Identifier: NCT01723865.

Feasibility of a cardiologist-only approach to sedation for electrical cardioversion of atrial fibrillation: a randomized, open-blinded, prospective study.

BACKGROUND/OBJECTIVES: Sedation with propofol should be administered by personnel trained in advanced airway management. To overcome this limitation, the use of short acting benzodiazepines by cardiologists spread widely, causing concerns about the safety of this procedure in the absence of anesthesiology assistance. The aim of the study was to compare feasibility of a cardiologist-only approach with an anesthesiologist-assisted sedation protocol during elective direct-current cardioversion (DCC) of persistent atrial fibrillation (AF). METHODS: This prospective, open-blinded, randomized study included 204 patients, which were admitted for scheduled cardioversion of persistent AF, and randomized in a 1:1 fashion to either propofol or midazolam treatment arm. Patients in the propofol group underwent DCC with anesthesiologist assistance, while patients in the midazolam group saw the cardiologist as the only responsible for both sedation and DCC. RESULTS: Twenty-three adverse events occurred: 13 in the propofol group and 10 in the midazolam group (p=NS). Most of them were related to bradyarrhythmias and respiratory depressions. There was no need of intubation or other advanced resuscitation techniques in any of these patients. No differences were found regarding procedure tolerability and safety endpoints between the two groups. DCC procedures with anesthesiology support were burdened by higher delay from scheduled time and higher costs. CONCLUSIONS: Sedation with midazolam administered by cardiologist-only appears to be as safe as sedation with propofol and anesthesiologist assistance. Adverse events were few in both groups and easily handled by the cardiologist alone. A cardiologist-only approach to sedation provides less procedural delay, thus being easier to schedule and correlated with fewer costs.

Remote monitoring for implantable defibrillators: a nationwide survey in Italy.

BACKGROUND: Remote monitoring (RM) permits home interrogation of implantable cardioverter defibrillator (ICD) and provides an alternative option to frequent in-person visits. OBJECTIVE: The Italia-RM survey aimed to investigate the current practice of ICD follow-up in Italy and to evaluate the adoption and routine use of RM. METHODS: An ad hoc questionnaire on RM adoption and resource use during in-clinic and remote follow-up sessions was completed in 206 Italian implanting centers. RESULTS: The frequency of routine in-clinic ICD visits was 2 per year in 158/206 (76.7%) centers, 3 per year in 37/206 (18.0%) centers, and 4 per year in 10/206 (4.9%) centers. Follow-up examinations were performed by a cardiologist in 203/206 (98.5%) centers, and by more than one health care worker in 184/206 (89.3%) centers. There were 137/206 (66.5%) responding centers that had already adopted an RM system, the proportion of ICD patients remotely monitored being 15% for single- and dual-chamber ICD and 20% for cardiac resynchronization therapy ICD. Remote ICD interrogations were scheduled every 3 months, and were performed by a cardiologist in 124/137 (90.5%) centers. After the adoption of RM, the mean time between in-clinic visits increased from 5 (SD 1) to 8 (SD 3) months (P<.001). CONCLUSIONS: In current clinical practice, in-clinic ICD follow-up visits consume a large amount of health care resources. The results of this survey show that RM has only partially been adopted in Italy and, although many centers have begun to implement RM in their clinical practice, the majority of their patients continue to be routinely followed-up by means of in-clinic visits.

Cardiac resynchronization therapy in patients undergoing atrioventricular junction ablation for permanent atrial fibrillation: a randomized trial.

AIMS: On the basis of the current knowledge, cardiac resynchronization therapy (CRT) cannot be recommended as a first-line treatment for patients with severely symptomatic permanent atrial fibrillation undergoing atrioventricular (AV) junction ablation. We examined whether CRT was superior to conventional right ventricular (RV) pacing in reducing heart failure (HF) events. METHODS AND RESULTS: In this prospective, multi-centre study, we randomly assigned 186 patients, in whom AV junction ablation and CRT device implantation had been successfully performed, to receive optimized echo-guided CRT (97 patients) or RV apical pacing (89 patients). The data were analysed according to the intention-to-treat principle. During a median follow-up of 20 months (interquartile range 11-24), the primary composite endpoint of death from HF, hospitalization due to HF, or worsening HF occurred in 11 (11%) patients in the CRT group and 23 (26%) patients in the RV group [CRT vs. RV group: sub-hazard ratio (SHR) 0.37 ( 95% CI 0.18-0.73), P = 0.005]. In the CRT group, compared with the RV group, fewer patients had worsening HF [SHR 0.27 (95% CI 0.12-0.58), P = 0.001] and hospitalizations for HF [SHR 0.20 (95% CI 0.06-0.72), P = 0.013]. Total mortality was similar in both groups [hazard ratio (HR) 1.57 (95% CI 0.58-4.27), P = 0.372]. The beneficial effects of CRT were consistent in patients who had ejection fraction ≤35%, New York Heart Association Class ≥III and QRS width ≥120 and in those who did not. At multi-variable Cox regression, only CRT mode remained an independent predictor of absence of clinical failure during the follow-up [HR = 0.23 (95% CI 0.08-0.66), P = 0.007]. CONCLUSIONS: In patients undergoing 'Ablate and Pace' therapy for severely symptomatic permanent atrial fibrillation, CRT is superior to RV apical pacing in reducing the clinical manifestations of HF. (ClinicalTrials.gov number: NCT00111527).

Usefulness of echo-guided cardiac resynchronization pacing in patients undergoing "ablate and pace" therapy for permanent atrial fibrillation and effects of heart rate regularization and left ventricular resynchronization.

An acute comparative study of right ventricular (RV) pacing and echocardiographically guided cardiac resynchronization pacing (CRP) was performed in patients who underwent "ablate and pace" therapy for permanent atrial fibrillation. It was hypothesized that optimized CRP guided by tissue Doppler echocardiography would exert an additive beneficial hemodynamic effect to that of rate regularization achieved through atrioventricular junction ablation. An acute intrapatient comparison of echocardiographic parameters was performed between baseline preablation values and RV pacing and CRP (performed <24 hours after ablation) in 50 patients. Optimized CRP configuration was defined as the modality of pacing corresponding to that of the shortest intra-left ventricular (LV) delay among simultaneous biventricular pacing, sequential biventricular pacing, and single-chamber pacing. The intra-LV delay was defined as the difference between the longest and the shortest activation time in the six basal segments of the left ventricle. Compared with preablation measures, the ejection fraction increased by 10.8% during RV pacing (19% in patients with intra-LV delays <47.5 ms and 3% in those with intra-LV delays >47.5 ms). Compared with RV pacing, CRP caused a 9.2% increase in the ejection fraction, a 6.8% decrease in LV systolic diameter, and a 17.3% decrease in mitral regurgitation area; LV dyssynchrony was reduced from 52 +/- 27 to 21 +/- 12 ms. Similar results were observed in patients with and without depressed systolic function and in patients with and without left bundle branch block. In conclusion, rate regularization achieved through atrioventricular junction ablation and RV pacing provides a favorable hemodynamic effect that is inversely related to the level of LV dyssynchrony. Minimizing LV dyssynchrony by means of optimized CRP yields an additional important benefit.

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.