AbstractAimsDetermine the feasibility of implementing a heart failure (HF) management strategy that (i) uses a device‐based, remote, dynamic, multimetric risk stratification model to predict the risk of HF events and (ii) uses a standardized, centrally administered, ambulatory medication intervention protocol to reproducibly and safely decrease elevated risk scores.Methods and resultsProspective, non‐randomized, single‐arm, multicenter feasibility study (Intervene‐HF) was conducted in HF patients implanted with a cardiac resynchronization therapy with implantable cardio defibrillator (CRT‐D) with TriageHF risk score feature. Certified HF nurses (CHFN) in the Medtronic Care Management Services Program implemented an ambulatory medication intervention strategy by following a standardized guided action pathway triggered by risk‐based alert. When CHFN received notification of increased risk score (HF care alert), they implemented a 3 day course of diuretic up‐titration (PRN) previously prescribed by a physician. Safety was monitored daily. Recovery after PRN was defined as ≥70% recovery of impedance toward baseline levels. Sixty‐six patients followed for 8.2 ± 3.9 months had 49 HF care alerts. Twenty‐three of 49 alerts did not receive PRN due to protocol‐mandated criteria. Twenty‐six of 49 alerts received PRN, 22 were completed, and 19 led to impedance recovery. Four interventions were stopped for safety without leading to an adverse event (AE). One of 26 PRNs was followed by a HF event. Eighty‐five per cent (22/26) of PRNs were completed without an AE; 69% (18/26) met the recovery criteria.ConclusionsThe Intervene‐HF study supports the feasibility of testing, in a large randomized clinical trial, an ambulatory medication intervention strategy that is physician‐directed, CHFN‐implemented, and based on individualized device risk stratification.

Abstract Background Diagnostic parameters measured in implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy defibrillators (CRTD) have been shown to change before and after heart failure (HF) events with fluid overload. Purpose We investigated the temporal characteristics of an integrated diagnostic risk score before and after HF events in a large real-world cohort of patients with ICD/CRTD devices. Methods We linked a de-identified database of aggregated electronic health record (EHR) data (2007–2017) to a manufacturer's device database with continuous diagnostic monitoring data. Patients with ICD/CRTD implants with intra-thoracic impedance diagnostic feature were included for this study. The previously defined integrated diagnostic risk score was derived by combining daily diagnostic data, including intra-thoracic impedance, night-time heart rate, activity, heart rate variability, and atrial fibrillation (AF) burden, ventricular rate during AF, CRT pacing, ventricular tachycardia episodes and shocks, in a Bayesian Belief Network framework. HF event was defined as an inpatient, emergency department, or observation unit stay in a hospital with primary diagnosis of HF and intravenous diuretic administration. Temporal average of daily risk score across all patients in the 60 days pre and post HF events were compared in HF events with and without readmission within 60 days and with no HF event during pre and post follow-up days. Results A total of 17,886 patients with 1.8±1.2 years of follow-up met inclusion criteria. The average age of patients was 66.6±12.3 years, with 72% being males, and 51% with ICD devices. The average integrated diagnostics risk score in HF events with and without readmission and with no events is shown in Figure. A total of 1174 patients had 1425 HF events with no readmission for HF within 60 days and 282 patients had 295 HF events which were followed by readmission for HF within 60 days. A total of 17,839 patients had no HF events over 86,858 follow-up months. The average daily risk score across all patients was higher on all 60 days pre and post HF event with readmission compared to HF events with no readmission (p<0.001) and both were higher compared to follow-up period with no events (p<0.001). The risk score recovers less often after HF events which are followed by readmission within 60 days compared to HF events with no readmission. Conclusions In a large real-world population of patients with ICD/CRTD devices, the average integrated diagnostics risk score was higher before and after HF events with readmission compared to HF events with no readmission. Re-admissions are more likely in patients with smaller risk score recovery after HF events. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Medtronic Plc

AbstractAimsThis study aimed to improve in‐person clinical evaluation on the day of heart failure (HF) hospitalization discharge by adding device‐measured parameters to predict 30 day HF rehospitalization risk in cardiac resynchronization therapy‐defibrillator (CRT‐D) patients.Methods and resultsIn a cohort of Medicare patients with CRT‐Ds, the independent prognostic value of four device‐measured parameters was assessed relative to typical clinical parameters associated with rehospitalization risk. Medicare registry, claims, and Medtronic CareLink® Network data for these patients were analysed using logistic regression modelling and net reclassification methods. Among 1563 CRT‐D patients, 411 patients had 607 HF hospitalization events during a median 6.3 years of follow‐up. Compared with clinical variables alone, impedance measurements resulted in a 28% improvement between the predicted probabilities of having vs. not having a 30 day HF rehospitalization (relative integrated discrimination improvement = 0.28) and a net 42% improvement in the classification of 30 day HF rehospitalization events and non‐events after an index HF hospitalization (net reclassification index = 0.42; 95% CI: 0.10, 0.74).ConclusionsIn CRT patients, intrathoracic impedance measurements improve prediction of 30 day HF rehospitalization over clinical characteristics alone. The present study provides supportive data for the routine evaluation of intrathoracic impedance prior to discharge in patient with CRT devices. Furthermore, the models developed in this study could be used to design interventions to improve compliance with Medicare reimbursement guidelines regarding 30 day HF rehospitalization.

Background Heart failure remains a leading cause of morbidity and mortality. Clinical prediction models provide suboptimal estimates of mortality in this population. We sought to determine the incremental value of implantable device diagnostics over clinical prediction models for mortality. Methods and Results RAFT (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial) patients with implanted devices capable of device diagnostic monitoring were included, and demographic and clinical parameters were used to compute Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) heart failure risk scores. Patients were classified according to MAGGIC score into low (0–16), intermediate (17–24), or high (>24) risk groups. Mortality was evaluated from 6 months postimplant in accordance with the RAFT protocol. In a subset of 1036 patients, multivariable analysis revealed that intermediate and high MAGGIC scores, fluid index, atrial fibrillation, and low activity flags were independent predictors of mortality. A device‐integrated diagnostic parameter that included a fluid index flag and either a positive atrial fibrillation flag or a positive activity flag was able to significantly differentiate higher from lower risk for mortality in the intermediate MAGGIC cohort. The effect was more pronounced in the high‐risk MAGGIC cohort, in which device‐integrated diagnostic–positive patients had a shorter time to death than those who were device‐integrated diagnostic negative. Conclusions Device diagnostics using a combination of fluid index trends, atrial fibrillation burden, and patient activity provide significant incremental prognostic value over clinical heart failure prediction scores in higher‐risk patients. This suggests that combining clinical and device diagnostic parameters may lead to models with better predictive power. Whether this risk is modifiable with early medical intervention would warrant further studies. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00251251.

Background Risk stratification models using integrated device diagnostics have been developed to predict heart failure (HF) events. However, effective management strategies to reduce this HF risk have not been developed. The purpose of the INTERVENE-HF study was to determine whether a physician-directed, nurse-implemented ambulatory medication intervention strategy could be safely and effectively instituted in HF patients with an increased HF risk score. Methods A prospective, non-randomized, single arm, multi-center feasibility study was conducted in HF patients implanted with a Medtronic CRT-D device with Triage HF dynamic risk score (HFRS) diagnostic feature. HFRS was based on Bayesian analysis of CRT-D measured variables: transthoracic impedance, heart rate, heart rate variability, arrhythmia parameters, and activity. Ambulatory medication intervention strategy was remotely implemented by certified HF nurses (CHFN) following a guided action pathway triggered by a risk based alert. CHFN received alert notification to evaluate a patient when there was an impedance based OptiVolTM fluid threshold crossing. Patients not excluded due to safety or protocol-mandated criteria were managed by CHFN using a personalized, 3 day course of diuretic up titration (PRN Tx) prescribed by a physician at enrollment. Safety was monitored through daily CHFN remote review of weight, blood pressure and symptoms. Sufficient recovery after PRN Tx was defined as ≥ 70% recovery of impedance to baseline levels on day 4. If recovery criterion was not met on day 4, a second PRN Tx was initiated and impedance was reassessed on day 8. Results 66 patients had the alert feature enabled and were followed by CHFNs for 8.2 ± 3.9 months. CHFNs received alerts triggered by 49 OptiVolTM crossings. 23 of 49 crossings were not acted on due to safety or protocol-mandated criteria. 26 of 49 crossings received PRN Tx, 19 with 1 round, 7 with two rounds. Of 26 PRN Tx, 22 were completed, 19 led to ≥ 70% impedance recovery within 4 - 8 days. 4 interventions were stopped early for safety without leading to a serious adverse event (AE). 1 of 26 PRN Tx was followed by a HF event within 30 days of PRN Tx. Safety endpoint (# of PRN Tx without PRN Tx AE / # of PRN Tx) was 22/26 (85%). Effectiveness endpoint (# recovered without HF event within 14 days and without PRN Tx AE / # of PRN Tx) was 18/26 (69%). Conclusion An individualized risk stratification based ambulatory medication intervention strategy that is physician-directed and CHFN-implemented can be safely and successfully instituted in HF patients using an integrated device diagnostics based HF risk score.

AimsTo determine adjusted associations among OptiVol® threshold crossings, long-term survival, and hospitalizations among heart failure (HF) patients with Medicare coverage in the United States.Methods and resultsA cohort with OptiVol®-enabled cardiac resynchronization therapy defibrillators (CRT-D) devices from the Implantable Cardioverter Defibrillator Registry was linked to both Medicare claims/summary data and Medtronic's CareLink® Network data. An extended multivariable Cox model was used to analyse associations among OptiVol® threshold crossings (treated as time-dependent covariates), mortality, and HF-related hospitalizations (HFH). We analysed N = 1565 patients with OptiVol®-enabled CRT-D devices (mean age 72.8, 28% women). The median follow-up was 6.3 years. Patients with >15.1% of days above OptiVol® threshold (highest quartile) had more than a 4-fold increase in mortality [hazard ratio (HR) 4.2, 95% confidence interval (CI): 3.3-5.3] and more than a 3-fold increase in HFH (HR 3.2, 95% CI: 2.4-4.2) compared with patients having <4.1% of days above threshold (lowest quartile) after adjustment for key covariates. In addition, a single OptiVol® crossing was associated with significantly increased rates of both mortality (HR 1.87, 95% CI: 1.27-2.75) and HFH (HR 1.70, 95% CI: 1.28-2.27).ConclusionIn a CRT-D cohort with over 6 years of follow-up, both single OptiVol® crossings and time above OptiVol® threshold were associated with increased rates of mortality and hospitalization, which has important implications for clinical care. This is the first study integrating device data with Medicare outcomes to validate the long-term significance of OptiVol® findings.

BACKGROUND:Insertable cardiac monitors (ICMs) are used for long-term ECG monitoring. The Reveal LINQ ICM has an improved atrial fibrillation (AF) detection algorithm. OBJECTIVE:The purpose of this study was to investigate the algorithm's real-world performance in patients with syncope, cryptogenic stroke, and known AF. METHODS:Consecutive patients with implanted ICM and AF detection parameters automatically set and maintained depending on the indication for monitoring were included. A single reviewer annotated all stored episodes after ICM implant. A second reviewer annotated a random sample of 10% of all detected AF episodes. The episode detection positive predictive value as well as true and false detection rates were determined for AF episodes of different durations. RESULTS:The study enrolled 3759 patients (1604 [43%] with syncope, 1049 [28%] with known AF, 1106 [29%] with cryptogenic stroke). Overall, 20,659 AF episodes were detected in 1020 patients. The gross episode detection positive predictive value was 84%, 73%, and 26% for all episodes (≥2 minutes) and improved to 97%, 95%, and 91% for detected AF episodes ≥1 hour in the syncope, known-AF, and cryptogenic stroke patient cohorts, respectively. The true (and false) detection rate was 0.23 (0.05), 3.8 (1.4), and 0.23 (0.65) per patient-month of monitoring for the syncope, known-AF, and cryptogenic stroke patient cohorts, respectively. Limiting ECG storage to the longest detected AF episode significantly reduced the burden of episode adjudication without significantly compromising the identification of patients with true AF. CONCLUSION:The performance of LINQ ICM is dependent on the AF incidence rate in the population being monitored, the programmed sensitivity of AF algorithm, and the duration of detected AF episodes.

Intrathoracic impedance threshold crossing has been associated with clinically relevant heart failure events and death in patients with chronic systolic heart failure; however, the impact of impedance threshold measurements on long-term clinical events and mortality in a real-world cohort of older patients with Medicare coverage is unknown. Furthermore, previous studies have not considered important covariates also potentially associated with heart failure mortality, such as NHYA class, hypertension, diabetes mellitus, and smoking status, which are available in the Medicare database.

BACKGROUND:Intrathoracic impedance-derived OptiVol fluid index calculated using implanted devices has been shown to predict mortality; direct measurements of impedance have not been examined. We hypothesized that baseline measured impedance predicts all-cause mortality; changes in measured impedance result in a change in the predicted mortality; and the prognostic value of measured impedance is additive to the calculated OptiVol fluid index.METHODS AND RESULTS:A retrospective analysis of 146,238 patients within the Medtronic CareLink database with implanted devices was performed. Baseline measured impedance was determined using daily values averaged from month 6 to 9 after implant and were used to divide patients into tertiles: group L = low impedance, ≤ 65 ohms; group M = medium impedance, 66 to 72 ohms; group H = high impedance, ≥ 73 ohms. Change in measured impedance was determined from values averaged from month 9 to 12 post implant compared with the 6- to 9-month values. OptiVol fluid index was calculated using published methods. All-cause mortality was assessed beginning 9 months post implant; changes in mortality was assessed beginning 12 months post implant. Baseline measured impedance predicted all-cause mortality; 5-year mortality for group L was 41%, M was 29%, and H was 25%, P < 0.001 among all groups. Changes in measured impedance resulted in a change in the predicted mortality; the prognostic value of measured impedance was additive to the OptiVol fluid index.CONCLUSIONS:Direct measurements of intrathoracic impedance using an implanted device can be used to stratify patients at varying mortality risk.

BACKGROUND:The characteristics of atrial fibrillation (AF) episodes in cryptogenic stroke patients have recently been explored in carefully selected patient populations. However, the incidence of AF among a large, real-world population of patients with an insertable cardiac monitor (ICM) placed for the detection of AF following a cryptogenic stroke has not been investigated.METHODS:Patients in the de-identified Medtronic DiscoveryLink™ database who received an ICM (Reveal LINQ™) for the purpose of AF detection following a cryptogenic stroke were included. AF detection rates (episodes ≥2 min) were quantified using Kaplan-Meier survival estimates at 1 and 6 months and compared to the CRYSTAL AF study at 6 months. The time to AF detection and maximum duration of AF episodes were also analyzed.RESULTS:A total of 1,247 patients (age 65.3 ± 13.0 years) were followed for 182 (IQR 182-182) days. A total of 1,521 AF episodes were detected in 147 patients, resulting in AF detection rates of 4.6 and 12.2% at 30 and 182 days, respectively, and representing a 37% relative increase over that reported in the CRYSTAL AF trial at 6 months. The median time to AF detection was 58 (IQR 11-101) days and the median duration of the longest detected AF episode was 3.4 (IQR 0.4-11.8) h.CONCLUSIONS:The real-world incidence of AF among patients being monitored with an ICM after a cryptogenic stroke validates the findings of the CRYSTAL AF trial and suggests that continuous cardiac rhythm monitoring for periods longer than the current guideline recommendation of 30 days may be warranted in the evaluation of patients with cryptogenic stroke.

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 (3310)), 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.

Introduction: The characteristics of atrial fibrillation (AF) episodes in cryptogenic stroke patients have recently been explored in carefully selected patient populations. However, the incidence and duration of AF episodes among a large, real-world population of unselected patients with an insertable cardiac monitor (ICM) placed for the detection of AF following a cryptogenic stroke have not been investigated. Methods: All patients in the de-identified Medtronic Discovery™ Link database who received an ICM (Reveal LINQ™) for the purpose of AF detection following a cryptogenic stroke and who had at least 30 days of device data were included. AF episodes underwent expert adjudication and were at least 2 minutes in duration. We quantified the AF detection rate using Kaplan-Meier survival estimates and compared this to the results from the CRYSTAL AF study, which rigorously excluded patients with evidence of AF prior to enrollment and ICM insertion. The maximum duration of AF episodes was also analyzed. Results: A total of 1247 patients were included and followed for 84±34 days. The mean age at the time of device insertion was 65.3±13.0 years. AF episodes (n=657) were detected in 91 patients, resulting in an AF detection rate of 9.22% at 120 days (Figure) which was 15% higher than CRYSTAL AF at the same time-point. The median duration of the longest detected AF episode was 3.9 [IQR 1.0-11.5] hours. Conclusions: AF episodes of clinically important durations were detected via continuous monitoring with ICMs in a significant proportion of cryptogenic stroke patients, despite relatively brief follow-up thus far. The real-world incidence of AF among patients being monitored with an ICM after a cryptogenic stroke appears to validate a recent randomized controlled trial and may be slightly higher when adjusted for the duration of follow-up, possibly due to differences in the rigor of the stroke work-up or inclusion/exclusion criteria.

BackgroundThe term “permanent” atrial fibrillation (AF) is generally used to describe the rhythm status of patients for whom cardioversion has failed or attempts to restore normal sinus rhythm (NSR) have ceased. However, the rhythm status of such patients is typically assessed by symptoms or intermittent monitoring, and therefore categorization may be imprecise.MethodsWe evaluated the presence of NSR among patients who were identified by their physicians as having permanent AF and who underwent prior insertion of a cardiac rhythm management device in the OMNI study. Patients with a dual‐ or triple‐chamber device (pacemaker, implantable cardiac defibrillator, or cardiac resynchronization therapy) and ≥30 days of device data were studied. We tabulated the percentage of follow‐up days spent entirely in NSR, entirely in AF, or in both NSR and AF.ResultsA total of 69 patients met inclusion criteria and were followed for 767 ± 479 days. More than 73% of patients experienced ≥1 entire day in NSR. On average, 38.2% of days were spent entirely in NSR, 11.8% of days were spent in a combination of NSR and AF, and only 50.0% of days were spent entirely in AF. The median daily AF burden during follow‐up was 14.6 [1.1–23.7] hours/day.ConclusionsNSR is common in many device patients thought to have permanent AF, suggesting that continuous arrhythmia monitoring could be useful in identifying permanent AF patients who may benefit from renewed rhythm control efforts. Alternatively, some permanent AF patients undergoing atrioventricular nodal ablation may benefit from dual‐chamber devices due to likely periods of NSR.

Reduction in Intrathoracic Impedance Reflects Deterioration in Renal Function in Heart Failure Patients