Use of healthcare claims to validate the Prevention of Arrhythmia Device Infection Trial cardiac implantable electronic device infection risk score.

AIM: The Prevention of Arrhythmia Device Infection Trial (PADIT) infection risk score, developed based on a large prospectively collected data set, identified five independent predictors of cardiac implantable electronic device (CIED) infection. We performed an independent validation of the risk score in a data set extracted from U.S. healthcare claims. METHODS AND RESULTS: Retrospective identification of index CIED procedures among patients aged ≥18 years with at least one record of a CIED procedure between January 2011 and September 2014 in a U.S health claims database. PADIT risk factors and major CIED infections (with system removal, invasive procedure without system removal, or infection-attributable death) were identified through diagnosis and procedure codes. The data set was randomized by PADIT score into Data Set A (60%) and Data Set B (40%). A frailty model allowing multiple procedures per patient was fit using Data Set A, with PADIT score as the only predictor, excluding patients with prior CIED infection. A data set of 54 042 index procedures among 51 623 patients with 574 infections was extracted. Among patients with no history of prior CIED infection, a 1 unit increase in the PADIT score was associated with a relative 28% increase in infection risk. Prior CIED infection was associated with significant incremental predictive value (HR 5.66, P < 0.0001) after adjusting for PADIT score. A Harrell's C-statistic for the PADIT score and history of prior CIED infection was 0.76. CONCLUSION: The PADIT risk score predicts increased CIED infection risk, identifying higher risk patients that could potentially benefit from targeted interventions to reduce the risk of CIED infection. Prior CIED infection confers incremental predictive value to the PADIT score.

First-in-Human Chronic Implant Experience of the Substernal Extravascular Implantable Cardioverter-Defibrillator.

OBJECTIVES: The aim of this study was to evaluate the safety and performance of an extravascular (EV) implantable cardioverter-defibrillator (ICD). BACKGROUND: Limitations of existing transvenous and subcutaneous ICD systems include lead reliability and morbidity issues associated with ICD lead implantation in the vasculature or lack of pacing therapies (e.g., antitachycardia pacing) in subcutaneous systems. The EV defibrillator uses a novel substernal lead placement to address these limitations. METHODS: This was a prospective, nonrandomized, chronic pilot study conducted at 4 centers in Australia and New Zealand. Participants were 21 patients referred for ICD implantation. Patients received EV ICD systems. Data collection included major systemic and procedural adverse events, defibrillation testing at implantation, and sensing and pacing thresholds. RESULTS: Among 20 patients who underwent successful implantation, the median defibrillation threshold was 15 J, and 90% passed defibrillation testing with a ≥10-J safety margin. Mean R-wave amplitude was 3.4 ± 2.0 mV, mean ventricular fibrillation amplitude was 2.8 ± 1.7 mV, and pacing was successful in 95% at ≤10 V. There were no intraprocedural complications. Two patients have undergone elective chronic system removal since hospital discharge. In the 15 patients presently implanted, the systems are stable in long-term follow-up. CONCLUSIONS: This first-in-human evaluation of an EV ICD demonstrated the feasibility of substernal lead placement, defibrillation, and pacing with a chronically implanted system. There were no acute major complications, and pacing, defibrillation, and sensing performance at implantation were successful in most patients. (Extravascular ICD Pilot Study [EV ICD]; NCT03608670).

Rhythm monitoring strategies in patients at high risk for atrial fibrillation and stroke: A comparative analysis from the REVEAL AF study.

BACKGROUND: Reducing atrial fibrillation (AF)-related stroke requires timely AF diagnosis, but the optimal monitoring strategy is unknown. OBJECTIVE: We used insertable cardiac monitor (ICM) data from the REVEAL AF study to compare AF detection rates by various short-term continuous monitoring (STM) strategies. METHODS AND RESULTS: Patients without known AF, but with CHADS2 scores ≥3 (or = 2 with ≥1 additional AF risk factor) received an ICM for AF detection. One-time STM strategies were assessed by computing AF incidence at 1, 2, 7, 14, and 30 days post-ICM insertion. Repeated STM strategies (quarterly 24-hour, 48-hour, 7-day, or monthly 24-hour monitoring) were modeled by randomly selecting day(s) within a 30-day window around each nominal evaluation date over a 1-year period (simulated 10,000 times). Endpoints included AF ≥6 minutes, AF ≥1 hour, and daily AF burden ≥1 and ≥ 5.5 hours. The impact of compliance on AF detection was evaluated using daily compliance rates of 85%, 75%, 65% and 55% during follow-up months 1-3, 4-6, 7-9, and 9-12, respectively. Based on data from 385 patients (71.5 ±â€¯9.9 years; CHADS2 score 3.0 ±â€¯1.0) the incidence of AF ≥6 minutes via ICM at 12 months was 27.1% (95% CI, 22.5-31.5%). This exceeded the range of estimated rates from all modeled one-time and repeated STM strategies (0.8% for 24-hour Holter monitoring to 10.6% for quarterly 7-day monitoring). Findings were similar for all AF endpoints. Modeled non-compliance reduced AF detection by 4.5% to 22.9%. CONCLUSIONS: Most AF episodes detected via ICMs would go undetected via conventional STM strategies, thus preventing optimal prophylaxis for adverse consequences.

Diurnal, Seasonal, and Monthly Variations in Ventricular Arrhythmias in Patients With Implantable Cardioverter-Defibrillators.

OBJECTIVES: The aim of this study was to assess the variations in ventricular arrhythmia (VA) occurrence according to seasons, months of the year, days of the week, and the time of day in a large implantable cardioverter-defibrillator patient population. BACKGROUND: Limited data exist on how VA occurrence varies as a function of time. METHODS: Data from 6 prospective studies were pooled to assess VA frequency over time. All adjudicated episodes of VAs ≤500 ms were included. VA distribution as a function of hour, day, month, and season were assessed through the construction of 4 negative binomial models. The models included a random patient effect and offset for days spent in each time period. RESULTS: Among 3,969 patients, 7,126.8 cumulative device-years with an average follow-up duration of 1.8 ± 1.4 years/patient were analyzed. VA occurrence was higher in the spring than the summer (0.86% vs. 0.70%; p = 0.009) but not significantly different from the fall (0.74%; p = 0.069) or winter (0.84%; p = 0.732). The estimated probability of occurrence of at least 1 VA episode in each 1-h block during the hours of 8 am to 10 pm over 365 days (0.10% to 0.12%) was higher (estimated 35% to 63% higher) than the referent period of midnight to 1 am (0.07%). No significant variations in VA occurrence were observed according to weekday and individual months of the year. CONCLUSIONS: Significantly higher VA occurrence in the spring and during the hours of 8 am to 10 pm were observed. Additional studies are needed to further understand the reasons for these observations, which may involve variations in temperature or differences in catecholamine triggers.

Changes in Management Following Detection of Previously Unknown Atrial Fibrillation by an Insertable Cardiac Monitor (from the REVEAL AF Study).

The REVEAL AF study demonstrated a high incidence of previously undetected atrial fibrillation (AF) using insertable cardiac monitors (ICMs) in patients with risk factors for AF and stroke. This analysis evaluated whether ICM monitoring led to changes in clinical management after AF detection. Patients with CHADS2 scores ≥3 (or =2 with ≥1 additional AF risk factor) but no history of AF received an ICM and were followed 18 to 30 months. Physicians recorded changes in clinical management in response to AF detection at scheduled (every 6 months) and unscheduled follow-up visits. Changes in clinical management included oral anticoagulation, rhythm or rate control pharmacotherapy, cardioversion, ablation, and cardiac subspecialist referral. In 387 patients who met inclusion criteria and received an ICM, AF was found in 115. A change in clinical management was taken in 87 patients with AF (76%). In 80 of these 87, a change was taken at the first visit after AF detection. In total, 31 patients (27%) with AF had ≥2 visits at which changes in clinical management were taken. The most common change was initiation of oral anticoagulation (n = 73, 63% of patients with AF). Patients with a change in clinical management at the first visit after AF detection tended to have longer AF episodes and a higher maximal daily AF burden compared with AF patients for whom no change was taken (longest episode: 52 vs 28 minutes; maximal daily AF burden:112 vs 23 minutes). Changes in management more frequently occurred at visits where patients reported AF-compatible symptoms (65% vs 46% of visits, p = 0.01). In conclusion, ICM monitoring to identify AF guides both immediate and long-term patient management in a population at high risk for stroke.

Therapy From a Novel Substernal Lead: The ASD2 Study.

OBJECTIVES: The ASD2 (Acute Extravascular Defibrillation, Pacing, and Electrogram) study evaluated the ability to adequately sense, pace, and defibrillate patients with a novel implantable cardioverter-defibrillator (ICD) lead implanted in the substernal space. BACKGROUND: Subcutaneous ICDs are an alternative to a transvenous defibrillator system when transvenous implantation is not possible or desired. An alternative extravascular system placing a lead under the sternum has the potential to reduce defibrillation energy and the ability to deliver pacing therapies. METHODS: An investigational lead was inserted into the substernal space via a minimally invasive subxiphoid access, and a cutaneous defibrillation patch or subcutaneous active can emulator was placed on the left mid-axillary line. Pacing thresholds and extracardiac stimulation were evaluated. Up to 2 episodes of ventricular fibrillation were induced to test defibrillation efficacy. RESULTS: The substernal lead was implanted in 79 patients, with a median implantation time of 12.0 ± 9.0 min. Ventricular pacing was successful in at least 1 vector in 76 of 78 patients (97.4%), and 72 of 78 (92.3%) patients had capture in ≥1 vector with no extracardiac stimulation. A 30-J shock successfully terminated 104 of 128 episodes (81.3%) of ventricular fibrillation in 69 patients. There were 7 adverse events in 6 patients causally (n = 5) or possibly (n = 2) related to the ASD2 procedure. CONCLUSIONS: The ASD2 study demonstrated the ability to pace, sense, and defibrillate using a lead designed specifically for the substernal space.

The interaction of sex, height, and QRS duration on the effects of cardiac resynchronization therapy on morbidity and mortality: an individual-patient data meta-analysis.

AIMS: To explore possible associations that may explain the greater benefit from cardiac resynchronization therapy (CRT) reported amongst women. METHODS AND RESULTS: In an individual-patient data meta-analysis of five randomized controlled trials, all-cause mortality and the composite of all-cause mortality or first hospitalization for heart failure (HF) were compared among 794 women and 2702 men assigned to CRT or a control group. Multivariable analyses were performed to assess the impact of sex, QRS duration, HF aetiology, left ventricular end-diastolic diameter (LVEDD), and height on outcome. Women were shorter, had smaller LVEDD, more often left bundle branch block, and less often ischaemic heart disease, but QRS duration was similar between sexes. Women tended to obtain greater benefit from CRT but sex was not an independent predictor of either outcome. For all-cause mortality, QRS duration was the only independent predictor of CRT benefit. For the composite outcome, height and QRS duration, but not sex, were independent predictors of CRT benefit. Further analysis suggested increasing benefit with increasing QRS duration amongst shorter patients, of whom a great proportion were women. CONCLUSIONS: In this individual-patient data meta-analysis, CRT benefit was greater in shorter patients, which may explain reports of enhanced CRT benefit among women. Further analyses are required to determine whether recommendations on the QRS threshold for CRT should be adjusted for height. (ClinicalTrials.gov numbers: NCT00170300, NCT00271154, NCT00251251).

Precision Medicine for Cardiac Resynchronization: Predicting Quality of Life Benefits for Individual Patients-An Analysis From 5 Clinical Trials.

BACKGROUND: Clinical trials have established the average benefit of cardiac resynchronization therapy (CRT), but estimating benefit for individual patients remains difficult because of the heterogeneity in treatment response. Accordingly, we created a multivariable model to predict changes in quality of life (QoL) with and without CRT. METHODS AND RESULTS: Patient-level data from 5 randomized trials comparing CRT with no CRT were used to create a prediction model of change in QoL at 3 months using a partial proportional odds model for no change, small, moderate, and large improvement, or deterioration of any magnitude. The C statistics for not worsening or obtaining at least a small, moderate, and large improvement were calculated. Among the 3614 patients, regardless of assigned treatment, 33.3% had a deterioration in QoL, 9.2% had no change, 9.2% had a small improvement, 13.5% had a moderate improvement, and the remaining 34.9% had a large improvement. Patients undergoing CRT were less likely to have a decrement in their QoL (28.2% versus 38.9%; P<0.001) and more likely to have a large QoL improvement (38.7% versus 30.6%; P<0.001). A partial proportional odds model identified baseline QoL, age, and an interaction of CRT with QRS duration as predictors of QoL benefits 3 months after randomization. C statistics of 0.65 for not worsening, 0.68 for at least a small improvement, 0.69 for at least a moderate improvement, and 0.73 for predicting a large improvement were observed. CONCLUSIONS: There is marked heterogeneity of treatment benefit of CRT that can be predicted based on baseline QoL, age, and QRS duration.

Characterization of health care utilization in patients receiving implantable cardioverter-defibrillator therapies: An analysis of the managed ventricular pacing trial.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are effective in terminating lethal arrhythmias, but little is known about the degree of health care utilization (HCU) after ICD therapies. OBJECTIVE: Using data from the managed ventricular pacing trial, we sought to identify the incidence and types of HCU in ICD patients after receiving ICD therapy (shocks or antitachycardia pacing [ATP]). METHODS: We analyzed HCU events (ventricular tachyarrhythmia [VTA]-related, heart failure-related, ICD implant procedure-related, ICD system-related, or other) and their association with ICD therapies (shocked ventricular tachycardia episode, ATP-terminated ventricular tachycardia episode, and inappropriately shocked episode). RESULTS: A total of 1879 HCUs occurred in 695 of 1030 subjects (80% primary prevention) and were classified as follows: 133 (7%) VTA-related, 373 (20%) heart failure-related, 97 (5%) implant procedure-related, 115 (6%) system-related, and 1160 (62%) other. Of 2113 treated VTA episodes, 1680 (80%) received ATP only and 433 (20%) received shocks. Stratifying VTA-related HCUs on the basis of the type of ICD therapy delivered, there were 25 HCUs per 100 shocked VTA episodes compared with 1 HCU per 100 ATP-terminated episodes. Inappropriate ICD shocks occurred in 8.7% of the subjects and were associated with 115 HCUs. The majority of HCUs (52%) began in the emergency department, and 66% of all HCUs resulted in hospitalization. CONCLUSION: For VTA-related HCUs, shocks are associated with a 25-fold increase in HCUs compared to VTAs treated by ATP only. Application of evidence-based strategies and automated device-based algorithms to reduce ICD shocks (higher rate cutoffs, use of ATP, and arrhythmia detection) may help reduce HCUs.

Predictors of short-term clinical response to cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with symptomatic heart failure and QRS prolongation but there is uncertainty about which patient characteristics predict short-term clinical response. METHODS AND RESULTS: In an individual patient meta-analysis of three double-blind, randomized trials, clinical composite score (CCS) at 6 months was compared in patients assigned to CRT programmed on or off. Treatment-covariate interactions were assessed to measure likelihood of improved CCS at 6 months. MIRACLE, MIRACLE ICD, and REVERSE trials contributed data for this analysis (n = 1591). Multivariable modelling identified QRS duration and left ventricular ejection fraction (LVEF) as predictors of CRT clinical response (P < 0.05). The odds ratio for a better CCS at 6 months increased by 3.7% for every 1% decrease in LVEF for patients assigned to CRT-on compared to CRT-off, and was greatest when QRS duration was between 160 and 180 ms. CONCLUSIONS: In symptomatic chronic heart failure patients (NYHA class II-IV), longer QRS duration and lower LVEF independently predict early clinical response to CRT.

Rationale and design of REVEAL AF: a prospective study of previously undiagnosed atrial fibrillation as documented by an insertable cardiac monitor in high-risk patients.

BACKGROUND: Atrial fibrillation (AF) is associated with substantial morbidity and mortality. Sometimes, AF exists but is undiagnosed; yet, its risk for consequences still exists. Identifying unrecognized episodes of AF in patients without known AF but at high risk for AF is critical for guiding preventative therapy decisions. The incidence of AF in high-risk patients, understanding how physicians manage these patients once AF has been detected, and knowing which patient characteristics are most predictive of developing AF are all unknown. METHODS: REVEAL AF is a prospective, single-arm, open-label, multicenter, interventional study to evaluate the incidence of AF ≥6 minutes in patients without known AF but who may be at high risk for AF based on symptoms and/or demographic criteria. The Reveal Insertable Cardiac Monitor will be implanted in 400 patients, and these patients will be followed up for a minimum of 18 months to monitor for the detection of AF, up to a maximum of 30 months or until the last patient has completed their 18-month follow-up visit. CONCLUSIONS: REVEAL AF will determine the incidence rate of AF lasting ≥6 minutes in patients who are at high risk for having AF. Secondary outcomes include observations regarding physician actions in response to detected AF and determination of risk markers for AF development.

An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure.

AIMS: Cardiac resynchronization therapy (CRT) with or without a defibrillator reduces morbidity and mortality in selected patients with heart failure (HF) but response can be variable. We sought to identify pre-implantation variables that predict the response to CRT in a meta-analysis using individual patient-data. METHODS AND RESULTS: An individual patient meta-analysis of five randomized trials, funded by Medtronic, comparing CRT either with no active device or with a defibrillator was conducted, including the following baseline variables: age, sex, New York Heart Association class, aetiology, QRS morphology, QRS duration, left ventricular ejection fraction (LVEF), and systolic blood pressure. Outcomes were all-cause mortality and first hospitalization for HF or death. Of 3782 patients in sinus rhythm, median (inter-quartile range) age was 66 (58-73) years, QRS duration was 160 (146-176) ms, LVEF was 24 (20-28)%, and 78% had left bundle branch block. A multivariable model suggested that only QRS duration predicted the magnitude of the effect of CRT on outcomes. Further analysis produced estimated hazard ratios for the effect of CRT on all-cause mortality and on the composite of first hospitalization for HF or death that suggested increasing benefit with increasing QRS duration, the 95% confidence bounds excluding 1.0 at ∼140 ms for each endpoint, suggesting a high probability of substantial benefit from CRT when QRS duration exceeds this value. CONCLUSION: QRS duration is a powerful predictor of the effects of CRT on morbidity and mortality in patients with symptomatic HF and left ventricular systolic dysfunction who are in sinus rhythm. QRS morphology did not provide additional information about clinical response. CLINICALTRIALSGOV NUMBERS: NCT00170300, NCT00271154, NCT00251251.

Biventricular pacing for atrioventricular block and systolic dysfunction.

BACKGROUND: Right ventricular pacing restores an adequate heart rate in patients with atrioventricular block, but high percentages of right ventricular apical pacing may promote left ventricular systolic dysfunction. We evaluated whether biventricular pacing might reduce mortality, morbidity, and adverse left ventricular remodeling in such patients. METHODS: We enrolled patients who had indications for pacing with atrioventricular block; New York Heart Association (NYHA) class I, II, or III heart failure; and a left ventricular ejection fraction of 50% or less. Patients received a cardiac-resynchronization pacemaker or implantable cardioverter-defibrillator (ICD) (the latter if the patient had an indication for defibrillation therapy) and were randomly assigned to standard right ventricular pacing or biventricular pacing. The primary outcome was the time to death from any cause, an urgent care visit for heart failure that required intravenous therapy, or a 15% or more increase in the left ventricular end-systolic volume index. RESULTS: Of 918 patients enrolled, 691 underwent randomization and were followed for an average of 37 months. The primary outcome occurred in 190 of 342 patients (55.6%) in the right-ventricular-pacing group, as compared with 160 of 349 (45.8%) in the biventricular-pacing group. Patients randomly assigned to biventricular pacing had a significantly lower incidence of the primary outcome over time than did those assigned to right ventricular pacing (hazard ratio, 0.74; 95% credible interval, 0.60 to 0.90); results were similar in the pacemaker and ICD groups. Left ventricular lead-related complications occurred in 6.4% of patients. CONCLUSIONS: Biventricular pacing was superior to conventional right ventricular pacing in patients with atrioventricular block and left ventricular systolic dysfunction with NYHA class I, II, or III heart failure. (Funded by Medtronic; BLOCK HF ClinicalTrials.gov number, NCT00267098.).

Combining shock reduction strategies to enhance ICD therapy: a role for computer modeling.

OBJECTIVES: To develop a computer model to test shock reduction strategies such as antitachycardia pacing and shock withholding for supraventricular rhythms, oversensing, and nonsustained ventricular tachycardia. BACKGROUND: While the implantable cardioverter defibrillator (ICD) can reduce mortality, inappropriate ICD shocks remain a limitation. Randomized trials provide evidence of efficacy, but they are not always practical. Computer models provide an alternative approach, and are particularly useful when evaluating multiple interventions. METHODS: A computer model was developed using clinical data and validated in a large ICD data set (EMPIRIC). After validation, the model was applied to 736 adjudicated clinical episodes from the ICD arm of Sudden Cardiac Death Heart Failure Trial (SCD-HeFT). RESULTS: The shock reduction strategies hypothetically reduced the number of VT/VF shocked episodes in SCD-HeFT by an estimated 59% (from 952 observed to 395 modeled shocks, probability of >0.999) at detection duration settings (18 of 24 intervals). The percentage of patients experiencing inappropriate shocks over 5 years was decreased by 15% (23.5-8.4%), and the number of shocks for non-VT/VF episodes was decreased from 423 to 77 (82% reduction). The percentage of patients receiving shocks for VT/VF was reduced from 30.7% (SCD-HeFT) to 26.1% with the addition of ATP. Extended detection (24 of 32 or 30 of 40 intervals) showed modest additional improvement compared to 18 of 24 intervals. CONCLUSION: Computer modeling is able to predict the results of a known clinical trial and demonstrate that shock reduction strategies have the potential to significantly reduce inappropriate and unnecessary ICD shocks versus the mandated programming used in SCD-HeFT.

Atrial pacing or ventricular backup-only pacing in implantable cardioverter-defibrillator patients.

BACKGROUND: The need for pacing support in typical ICD patients is unknown. OBJECTIVE: This study sought to determine whether atrial pacing with ventricular backup pacing is equivalent to ventricular backup pacing only in implantable cardioverter-defibrillator (ICD) patients. METHODS: We randomized 1,030 patients from 84 sites with indications for ICDs, with sinus rhythm, and without symptomatic bradycardia to atrial pacing with ventricular backup at 60 beats/min (518) or ventricular backup pacing at 40 beats/min (512). The primary end points were time to death, heart failure hospitalization (HFH), and heart failure-related urgent care (HFUC). RESULTS: Follow-up was 2.4 ± 0.8 years when the trial was stopped for futility. There were 355 end point events (103 deaths, 252 HFH/HFUC) in 194 patients favoring ventricular backup pacing (event-free rate 77.7% vs. 80.3% for atrial pacing at 30 months; hazard ratio 1.14, upper confidence bound 1.59, prespecified noninferiority threshold 1.21), therefore equivalence between pacing arms was not demonstrated. Overall HFH/HFUC rates were slightly higher during atrial pacing (event-free rate 85.4% vs. 86.4% for ventricular backup pacing). Exploratory analyses revealed that the difference in HFH/HFUC rates was largely seen in patients with a PR interval ≥230 ms. There were no differences between groups for atrial fibrillation, ventricular tachycardia/ventricular fibrillation, quality of life, or echocardiographic measurements. Fewer patients in the atrial pacing group were reported to develop an indication for bradycardia pacing (3.7% vs. 7.3%, P = .0053). CONCLUSION: Equivalence between atrial pacing and ventricular backup pacing only could not be demonstrated. CLINICAL TRIALS IDENTIFIER: NCT00281099.

Differences in effects of electrical therapy type for ventricular arrhythmias on mortality in implantable cardioverter-defibrillator patients.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) shocks have been associated with an increased risk of death. It is unknown whether this is due to the ventricular arrhythmia (VA) or shocks and whether antitachycardia pacing (ATP) termination can reduce this risk. OBJECTIVE: The purpose of this study was to determine whether mortality in ICD patients is influenced by the type of therapy (shocks of ATP) delivered. METHODS: Cox models evaluated effects of baseline characteristics, ventricular tachycardia (VT; <188 bpm), fast VT (FVT; 188-250 bpm), ventricular fibrillation (VF; >250 bpm), and therapy type (shocks or ATP) on mortality among 2135 patients in four trials of ATP to reduce shocks. RESULTS: Over 10.8 +/- 3.3 months, 24.3% patients received appropriate shocks (50.6%) or ATP only (49.4%), and 6.6% died. Mortality predictors were age (hazard ratio 1.07, 95% confidence interval 1.04-1.08, P <.0001), New York Heart Association class III/IV (3.50 [2.27-5.41]; P <.0001), coronary disease (3.08 [1.31-7.25]; P = .01), and cumulative VA (VT + FVT + VF) episodes shocked (1.20 [1.13, 1.29]; P <.0001). Beta-blockers (0.65, 0.46-0.92; P <.0001) and remote myocardial infarction (0.53, [0.38-0.76] P = .0004) predicted reduced risk. Since 92% of VT and all VF received a single therapy type (ATP and shocks, respectively), the effect of therapy on episode risk could not be established. For FVT (32% shocked, 68% ATP), episode and therapy effects could be uncoupled; ATP-terminated FVT did not increase episode mortality risk, whereas shocked FVT increased risk by 32%. Survival rates were highest among patients with no VA (93.8%) of ATP-only (94.7%) and lowest for shocked patients (88.4%). Monthly episode rates were 80% higher among shocked versus ATP-only patients. CONCLUSIONS: Shocked VA episodes are associated with increased mortality risk. Shocked patients have substantially higher VA episode burden and poorer survival compared with ATP-only-treated patients.

Trial design of the clinical evaluation of remote notification to reduce time to clinical decision: the Clinical evaluation Of remote NotificatioN to rEduCe Time to clinical decision (CONNECT) study.

BACKGROUND: Indications for implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy defibrillators have greatly expanded in the last 5 years, encompassing a wider variety of patients with a multitude of comorbidities. To meet the needs of these patients, the managing clinicians need to streamline their follow-up care. New ICD/cardiac resynchronization therapy defibrillators provide enhanced device status and disease progression remote monitoring capabilities that support more comprehensive and efficient follow-ups. In addition, this monitoring between follow-ups is likely to impact health care utilization. METHODS AND RESULTS: The Clinical evaluation Of remote NotificatioN to rEduCe Time to clinical decision (CONNECT) study will randomize approximately 2,000 patients implanted with an ICD with or without CRT capabilities from 150 sites in the United States to remote monitoring versus standard in-office care. This study will evaluate the time from clinical event to clinical decision in response to the event, as well as the associated impact on health care utilization and quality of life. Patients monitored remotely will be provided a home monitor for transmitting device diagnostics to the clinician's office. These devices will use wireless telemetry, allowing the automatic transmission of diagnostics to the office without the need for patient intervention. Patients receiving in-office care will be followed in the office at a fixed schedule and without remote monitoring. All patients will be followed for 15 months postimplant. CONCLUSION: The CONNECT study is evaluating the impact of remote monitoring and early notification using wireless telemetry on the time to clinical decisions, the allocation of health care utilization, and quality of life. Results from this study are expected mid-2009.

Design of the Pacemaker REmote Follow-up Evaluation and Review (PREFER) trial to assess the clinical value of the remote pacemaker interrogation in the management of pacemaker patients.

BACKGROUND: Although pacemakers are primarily used for the treatment of bradycardia, diagnostic data available in current pacemakers allow them to be also used as sophisticated, continuous monitoring devices. Easy access to these stored data may assist clinicians in making diagnostic and therapeutic decisions sooner, thus avoiding potential long-term sequelae due to untreated clinical disorders. Internet-based remote device interrogation systems provide clinicians with frequent and complete access to stored data in pacemakers. In addition to monitoring device function, remote monitors may be a helpful tool in assisting physicians in the management of common arrhythmia disorders. METHODS: The Pacemaker REmote Follow-up Evaluation and Review (PREFER) trial is a prospective, randomized, parallel, unblinded, multicenter, open label clinical trial to determine the utility of remote pacemaker interrogation in the earlier diagnosis of clinically actionable events compared to the existing practice of transtelephonic monitoring. There have been 980 patients enrolled and randomized to receive pacemaker follow up with either remote interrogation using the Medtronic CareLink(R) Network (CareLink) versus the conventional method of transtelephonic monitoring (TTM) in addition to periodic in-person interrogation and programming evaluations. The purpose of this manuscript is to describe the design of the PREFER trial. The results, to be presented separately, will characterize the number of clinically actionable events as a result of pacemaker follow-up using remote interrogation instead of TTM. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00294645.

The influence of symptoms and device detected atrial tachyarrhythmias on medical management: insights from A-HIRATE.

BACKGROUND: The influence of symptoms and device-detected atrial tachyarrhythmias (AT) on the management of AT in a pacemaker population has not been well described. We report the influence of symptoms and device detected AT on pharmacological disease management. METHODS: Group 1 (n = 331) included patients without and Group 2 (n = 96) included patients with prior history of AT with an approved pacemaker indication. Dual chamber pacemakers, (kappa 700 or kappa 900, Medtronic, Minneapolis, MN, USA) were implanted. The impact of symptoms, AT burden, a history of AT, and time since implant on changes in the use of anticoagulation, beta-blockers, and antiarrhythmic drugs was analyzed. RESULTS: A total of 232 patients experienced at least one atrial high rate episode (AHRE). AT burden was higher in Group 2. Symptoms were reported by 154 patients in Group 1 and 47 patients in Group 2. Among patients experiencing AHRE, symptoms were reported in 17 patients in Group 1 (5.3%) and 22 patients in Group 2 (24.7%). Changes in antiarrhythmic drugs and anticoagulation were influenced by history of AT and AT burden, while changes in the use of beta-blockers were influenced by symptoms. The probability of a pharmacologic therapy change decreased with time since implant for all agents except coumadin. CONCLUSION: Pharmacologic AT therapy is differentially influenced by patient-reported symptoms of AT compared to device-detected asymptomatic AT. Anticoagulation and antiarrhythmic therapies are influenced by device detection of asymptomatic AT, whereas initiation of beta-blockers is more strongly influenced by symptoms.

Asymptomatic atrial fibrillation in pacemaker recipients: incidence, progression, and determinants based on the atrial high rate trial.

BACKGROUND: The epidemiology and clinical implications of asymptomatic atrial tachyarrhythmias (AT) including both atrial fibrillation and flutter in pacemaker recipients with and without arrhythmia history are not well understood. The Atrial High Rate Episodes (A-HIRATE) in Pacemaker Patients Trial was designed to identify and compare the incidence of AT in patients with and without previously diagnosed AT and a standard indication for dual chamber pacing, and to provide useful diagnostic information for clinical management. METHODS: Four hundred twenty-seven patients were implanted with a pacemaker (Kappa 7-900, Medtronic, Inc., Minneapolis, MN, USA) capable of detecting and storing multiple atrial high rate episodes (AHRE) and followed for 2 years. Group I included 331 patients without prior history of AT and Group II included 96 patients with prior AT history. RESULTS: Pacemaker diagnostics appropriately detected 93% of reviewed AHRE. The rate of occurrence of first AHRE was significantly higher (P < 0.0001) in Group II patients, as was average AHRE burden. The rate of first AHRE occurrence was 88.6% for patients in Group II and 53.8% in Group I at 24 months post-implant. The rate of AHRE occurrence was similar in both groups after the first month post-implant. The majority of stored AHRE were asymptomatic; symptoms did not correspond to an actual AHRE in most patients. CONCLUSIONS: The incidence of AT in pacemaker recipients is high. Most device-detected AHRE are asymptomatic. Prior history of AT is associated with higher arrhythmia burden. AHRE diagnostics have a high positive predictive value for identifying AT events.