Personalized monitoring of electrical remodelling during atrial fibrillation progression via remote transmissions from implantable devices.

AIMS: Atrial electrical remodelling (AER) is a transitional period associated with the progression and long-term maintenance of atrial fibrillation (AF). We aimed to study the progression of AER in individual patients with implantable devices and AF episodes. METHODS AND RESULTS: Observational multicentre study (51 centres) including 4618 patients with implantable cardioverter-defibrillator +/-resynchronization therapy (ICD/CRT-D) and 352 patients (2 centres) with pacemakers (median follow-up: 3.4 years). Atrial activation rate (AAR) was quantified as the frequency of the dominant peak in the signal spectrum of AF episodes with atrial bipolar electrograms. Patients with complete progression of AER, from paroxysmal AF episodes to electrically remodelled persistent AF, were used to depict patient-specific AER slopes. A total of 34 712 AF tracings from 830 patients (87 with pacemakers) were suitable for the study. Complete progression of AER was documented in 216 patients (16 with pacemakers). Patients with persistent AF after completion of AER showed ∼30% faster AAR than patients with paroxysmal AF. The slope of AAR changes during AF progression revealed patient-specific patterns that correlated with the time-to-completion of AER (R2 = 0.85). Pacemaker patients were older than patients with ICD/CRT-Ds (78.3 vs. 67.2 year olds, respectively, P < 0.001) and had a shorter median time-to-completion of AER (24.9 vs. 93.5 days, respectively, P = 0.016). Remote transmissions in patients with ICD/CRT-D devices enabled the estimation of the time-to-completion of AER using the predicted slope of AAR changes from initiation to completion of electrical remodelling (R2 = 0.45). CONCLUSION: The AF progression shows patient-specific patterns of AER, which can be estimated using available remote-monitoring technology.

Patient satisfaction with remote monitoring of cardiac implantable electronic devices: the VALIOSA questionnaire.

BACKGROUND: Remote monitoring of cardiac implantable electronic devices (CIEDs) has demonstrated substantial benefits. Treatment guidelines have therefore endorsed its use and is being increasingly adopted in the clinical setting, but the level of satisfaction they convey remains still unknown. We developed and validated a questionnaire to measure patient satisfaction with remote monitoring using Medtronic CareLink® Network and assessed its internal reliability and dimensional validity. METHODS: After a thorough literature review, cognitive debriefing of 18 patients, and an expert panel discussion, a 30-item instrument was proposed and grouped into 5 dimensions (items): 1- Information on cardiac condition (3), 2- Device convenience (3), 3- Transmission process (6), 4- Satisfaction with medical monitoring (8), and 5- General opinions (10). Correlation with the visual analog scale (VAS), overall health related quality of life (HRQoL) measured by the EuroQoL-5D accompanied by the VAS as well as with the Medical Outcomes Study (MOS) SF-36 were assessed. Psychometric properties, exploratory factor analysis and a second order confirmatory factor analysis (a hierarchical CFA with a general common factor explaining the relations between the first order common factors, See Figure 1) were estimated. Models were assessed based on item loading size, sign and statistical significance, and goodness-of-fit statistics. RESULTS: A total of 186 patients (77% male) with a mean age of 66.03 (SD = 13.94) years were assessed. 48% had implantable cardioverter-defibrillators, 24% had pacemakers, and 29% had cardiac resynchronization therapy devices. An overall Cronbach's α = 0.893 was achieved, with acceptable reliabilities for isolated dimensions. Correlations with corresponding VAS scales were meaningful and significant (p < 0.01). The second order factor solution yielded good goodness-of-fit indexes (χ2/df = 1.44, CFI = 0.96, TLI = 0.95, RMSEA = 0.05). Satisfaction with remote monitoring was not related to HRQoL (r < 0.05), except for the correlation between the SF-36 mental component and the information on cardiac condition dimension (r = 0.263, p < 0.001). CONCLUSIONS: The 30-item questionnaire showed good reliability and validity to assess satisfaction with remote monitoring in patients with CIEDs.

Safety and efficiency of a common and simplified protocol for pacemaker and defibrillator surveillance based on remote monitoring only: a long-term randomized trial (RM-ALONE).

AIMS: This trial aimed to evaluate the safety and efficiency of a common and simplified protocol for the surveillance of cardiac implantable electronic devices based on remote monitoring (RM) in patients with pacemakers (PMs) and implantable cardiac defibrillators (ICDs) for at least 24 months. METHODS AND RESULTS: The RM-ALONE is a multicentre prospective trial that randomly assigned 445 patients in two groups, both followed by RM: the home monitoring-only (HMo) based on RM + remote interrogations (RIs) every 6 months and the HM + IO that adds in-office evaluations every 6 months to RM. Four hundred and forty-five patients were enrolled in the study, 294 PMs and 151 ICDs recipients. In the HMo group, 20% of patients experienced ≥1 major adverse cardiac event (MACE) vs. 19.5% in HM + IO group (P = 0.006 for non-inferiority). The proportion of patients with a PM/ICD who experienced ≥1 MACE was 15.2/29.3% in HMo group and 16.1/26.3% in HM + IO group (hazard ratio 0.95/1.15, 95% confidence interval 0.53-1.70/0.62-2.10). There were 789 in-office evaluations (136 in the HMo and 653 in the HM + IO; P < 0.001). There was a 79.2% reduction of in-office evaluations with no significant differences in unscheduled visits between groups: 122 (54.5%) in HMo and 101 (45.3%) in HM + IO; P = 0.15. The time a physician/nurse spent per patient/follow-up was significantly reduced in the HMo group: 4/5 min (0-30)/(1-30) vs. 10/10 min (0-40)/(1-40) in HM + IO (P < 0.0001). CONCLUSION: The RM-ALONE protocol common for ICD and PM surveillance, consisting of RM + RI every 6 months has proven safe and efficient in reducing hospital visits and staff workload.

Premature ventricular contractions in patients with an implantable cardioverter defibrillator cardiac resynchronization therapy device: Results from the UMBRELLA registry.

BACKGROUND: Premature ventricular contractions (PVC) are known to reduce the percentage of biventricular (BiV) pacing in patients with cardiac resynchronization (CRT), decreasing the clinical response. The aim of this study was to evaluate the prevalence of a high PVC burden, as well as therapeutic action (pharmacotherapy, catheter ablation or device programming), in a large CRT implantable-defibrillator (CRT-D) population. METHODS: Patients with a CRT-D device from the UMBRELLA multicenter prospective remote monitoring registry were included. The PVC count was collected from each remote monitoring transmission. Patients were divided into two high (≥1 transmission ≥200/≥400 PVC/h, respectively) and one low (all transmissions <200 PVC/h) PVC count groups. The PVC burden following a high PVC count transmission was calculated. RESULTS: Of 1268 patients, 135 (11%) and 43 (3.4%) presented high PVC count (≥200/≥400 PVC/h, respectively). The majority of patients in the high PVC groups were not treated (61 [79%] and 32 [74%], respectively. Considering the untreated patients in the high PVC groups, median PVC/h was 199 (interquartile range [IQR]: 196) and 271 (IQR: 330), respectively. The PVC burden (proportion of time with PVC/h ≥ 200/≥400) was 40% (IQR 70) and 29% (IQR 59), respectively. CONCLUSION: A significant proportion of CRT-D patients presented a high PVC count, however, few received treatment. In the untreated patients with a high PVC count, the PVC burden during follow-up varied substantially. Several consecutive recordings of a high PVC count should be warranted before considering therapeutic action such as catheter ablation.

Association of cardiac resynchronization therapy with the incidence of appropriate implantable cardiac defibrillator therapies in ischaemic and non-ischaemic cardiomyopathy.

AIMS: Cardiac resynchronization therapy (CRT) reduces the incidence of sudden cardiac death and the use of appropriate implantable cardioverter-defibrillator (ICD) therapies (AICDTs); however, this antiarrhythmic effect is only observed in certain groups of patients. To gain insight into the effects of CRT on ventricular arrhythmia (VA) burden, we compared the incidence of AICDT use in four groups of patients: patients with ischaemic cardiomyopathy vs. non-ischaemic dilated cardiomyopathy (NIDC) and patients implanted with an ICD vs. CRT-ICD. METHODS AND RESULTS: We analysed 689 consecutive patients (mean follow-up 37 ± 16 months) included in the Umbrella registry, a multicentre prospective registry including patients implanted with ICD or CRT-ICD devices with remote monitoring capabilities in 48 Spanish Hospitals. The primary outcome was the time to first AICDT. Despite a worse clinical risk profile, NIDC patients receiving a CRT-ICD had a lower cumulative probability of first AICDT use at 2 years compared with patients implanted with an ICD [24.7 vs. 41.6%, hazard ratio (HR): 0.49, P = 0.003]; on the other hand, there were no significant differences in the incidence of first AICDT use at 2 years in ischaemic patients (22.6 vs. 21.9%, P = NS). Multivariate analysis confirmed the association of CRT with lower AICDT rates amongst NIDC patients (Adjusted HR: 0.55, CI 95% 0.35-0.87). CONCLUSIONS: These data suggest that CRT is associated with significantly lower rates of first AICDT use in NIDC patients, but not in ischaemic patients. This study suggests that ICD patients with NIDC and left bundle branch block experiencing VAs may benefit from an upgrade to CRT-ICD despite being in a good functional class.

Incidence of arrhythmias in a large cohort of patients with current implantable cardioverter-defibrillators in Spain: results from the UMBRELLA Registry.

AIMS: The benefit of implantable cardioverter-defibrillators (ICDs) in patients at risk of sudden death has been established in randomized clinical trials (RCTs) using the ICD models available at the time. However, observational large-scale data on the incidence of arrhythmias in up-to-date ICDs implanted according to the current guidelines are scarce. The aim was to assess the incidence of arrhythmias in a large, current ICD population based on a blinded peer review of the detected episodes. METHODS AND RESULTS: UMBRELLA is a multicentre, observational registry of ICD patients followed by remote monitoring. Stored episodes were classified by a blinded committee of experts. Subgroup analyses were based on clinical profiles established by previous pivotal RCTs of ICDs. Of 1514 enrolled patients, 605 (39.9%) patients had 5951 episodes after 26 ± 17 months follow-up, being 3353 of them (56.3%) sustained ventricular arrhythmias (SVA), and 13.2% of SVA were self-terminated. Appropriate and inappropriate shocks occurred in 11.6 and 5% of patients, respectively. The 3 years cumulative incidence of SVA was 25% (95% CI: 21-28%) in primary prevention patients and 41% (95% CI: 36-47%) in secondary prevention patients (P < 0.001). Male gender, secondary prevention, and atrial fibrillation as basal rhythm were significantly related to a higher incidence of SVA. CONCLUSION: This real-world analysis suggests that modern ICD patients have a low rate of appropriate and inappropriate shocks. The risk of SVA in secondary prevention patients is less than what has been reported in RCTs.

Different impact of long-detection interval and anti-tachycardia pacing in reducing unnecessary shocks: data from the ADVANCE III trial.

AIMS: A long-detection interval (LDI) (30/40 intervals) has been proved to be superior to a standard-detection interval (SDI) (18/24 intervals) in terms of reducing unnecessary implantable cardioverter defibrillator (ICD) therapies. To better evaluate the different impact of LDI and anti-tachycardia pacing (ATP) on reducing painful shocks, we assessed all treated episodes in the ADVANCE III trial. METHODS AND RESULTS: A total of 452 fast (200 ms < cycle length ≤ 320 ms) arrhythmic episodes were recorded: 284 in 138 patients in the SDI arm and 168 in 82 patients in the LDI arm (106/452 inappropriate detections). A total of 346 fast ventricular tachycardias (FVT) were detected in 169 patients: 208 in 105 patients with SDI and 138 in 64 patients with LDI. Setting LDI determined a significant reduction in appropriate but unnecessary therapies [208 in SDI vs. 138 in LDI; incidence rate ratio (IRR): 0.61 (95% CI 0.45-0.83), P = 0.002]. Anti-tachycardia pacing determined another 52% reduction in unnecessary shocks [208 in SDI with hypothetical shock-only programming vs. 66 in LDI with ATP; IRR: 0.37 (95% CI 0.25-0.53, P < 0.001)]. The efficacy of ATP in terminating FVT was 63% in SDI and 52% in LDI (P = 0.022). No difference in the safety profile (acceleration/degeneration and death/cardiovascular hospitalizations) was observed between the two groups. CONCLUSION: The combination of LDI and ATP during charging is extremely effective and significantly reduces appropriate but unnecessary therapies. The use of LDI alone yielded a 39% reduction in appropriate but unnecessary therapies; ATP on top of LDI determined another 52% reduction in unnecessary shocks. The strategy of associating ATP and LDI could be considered in the majority of ICD recipients.

Etiology and Programming Effects on Shock Efficacy in ICD Recipients.

BACKGROUND: We sought to assess the efficacy of high-energy shocks to restore rhythm and predictors of success in patients with sustained ventricular arrhythmias and implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: Data from 162 patients included in the UMBRELLA study that experienced one or more episodes of ventricular tachycardia (VT) for which ICD shocks of at least 30 Joules were delivered (appropriate high-energy shocks) were analyzed. In total, 456 ventricular arrhythmia episodes were registered. Forty four episodes (9.6%) from 39 patients (24%) had at least one ineffective high-energy shock delivered. Hypertrophic cardiomyopathy was more frequent among patients with unsuccessful shocks (10.3% vs 2.4%). Patients with ineffective shocks had higher proportion of sustained monomorphic ventricular arrhythmias (86.4%; the other 13.6% were sustained polymorphic and ventricular fibrillation [VF]) compared with patients with all their shocks effective (62.9%, P = 0.02). No statistical differences were found between groups in time from detection to the high-energy shock delivery, in tachycardia cycle length, or in antitachycardia pacing, but patients with ineffective high-energy shocks had higher proportion of previously ineffective low-energy shock (9.1% vs 0.5%, P = 0.01). CONCLUSION: We found a substantial rate of ineffective high-energy shocks for the treatment of VT or VF in patients with ICD. High-energy shock efficacy seems to be reduced by hypertrophic cardiomyopathy and by the administration of previous low-energy shocks.

Atrial Rate-Responsive Pacing and Incidence of Sustained Atrial Arrhythmias in Patients with Implantable Cardioverter Defibrillators.

BACKGROUND: Atrial rate-responsive pacing (RRP) has proved to be safe in pacemaker recipients with chronotropic incompetence. Although RRP is available in all current implantable cardioverter defibrillators (ICDs), the outcomes of this pacing mode in ICD patients are unknown. The aim is to evaluate the relationship between atrial RRP and atrial arrhythmias in ICD recipients. METHODS: Dual-chamber and triple-chamber ICD patients were included in this multicenter cohort study. Patients with permanent atrial fibrillation (AF) or VVI pacing mode were excluded. The number and duration of atrial tachycardia (AT)/AF episodes were assessed. RESULTS: Data from 415 patients and 80,707 AT/AF episodes (median duration: 0.4 hours) were collected after a 21.3 ± 14.1-month follow-up. Atrial RRP was programmed in 90 (21.7%) patients and was associated with a higher atrial pacing percentage in the overall study population (51.2 ± 33.8% vs 18.4 ± 25.7%, P < 0.001) and to a higher ventricular pacing percentage among dual-chamber devices (22.3 ± 37.6% vs 9.3 ± 25%, P < 0.001). Independent factors associated with sustained AT/AF episodes (>23 hours) were previous AF (odds ratio [OR]: 7.98; 95% confidence interval [CI]: 4.11-15.47; P < 0.001) and atrial RRP (OR: 3.58; 95% CI: 1.82-7.03; P < 0.001). RRP was related to a lower sustained AT/AF episodes-free survival both in patients with a history of AF (43% vs 70%, P = 0.035) and without a history of AF (82% vs 97%, P = 0.004) at 2 years. CONCLUSIONS: Atrial RRP in ICD patients was related to a higher incidence of sustained atrial arrhythmias. This pacing mode may have an atrial proarrhythmic effect on ICD patients, especially among those with a history of AF.

An Automatic Algorithm Based on Morphological Stability During Fast Ventricular Arrhythmias Predicts Successful Antitachycardia Pacing in ICD Patients: A Multicenter Study.

BACKGROUND: Different types of ventricular arrhythmias (monomorphic ventricular tachycardia [VT], polymorphic VT, or ventricular fibrillation) can be detected by implantable cardiac defibrillators (ICDs) in fast VT zone. The efficacy of antitachycardia pacing (ATP) depends on the type of the treated arrhythmia. We hypothesized that an automatic algorithm based on morphological affinity of ICD far-field electrograms during tachycardia can predict ATP success and the need of shock. METHODS: The algorithm was evaluated on ventricular arrhythmias recorded in CareLink ICD remote monitoring system (Medtronic Inc., Minneapolis, MN, USA). Patients were selected if first ATP programmed was a burst of eight pulses at 88% coupling interval and if a far-field electrogram was available. The algorithm calculated a stability coefficient (SC) for all their stored ATP-treated fast ventricular arrhythmia (VA) episodes (LC 200-300 ms), analyzing the morphology homogeneity of the last eight recorded far-field electrograms before ventricular arrhythmias detection. RESULTS: Inclusion criteria were fulfilled by 717 patients from 29 centers. Three hundred and twenty fast VA were recorded in 103 patients. A higher SC was observed in episodes terminated with the first-ATP (0.78 [0.72-0.84] vs 0.74 [0.60-0.84]; P = 0.006). These differences were especially marked among the 62 episodes of very fast VA (CL ≤250 ms) (0.77 [0.74-0.85] vs 0.64 [0.51-0.8]; P = 0.006). In the multivariate analysis, a SC > 70% was independently associated with a higher likelihood of first-ATP success (odds ratio [OR] = 2.5; [95% confidence interval (CI) = 1.4-4.5], P = 0.001) and a lower need of shock (OR = 0.37; [95% CI = 0.2-0.7], P = 0.002). CONCLUSION: This automatic algorithm (stability coefficient) shows that ATP therapy response can be predicted in fast ventricular arrhythmias through morphology evaluation.

Efficacy of long detection interval implantable cardioverter-defibrillator settings in secondary prevention population: data from the Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients III (ADVANCE III) trial.

BACKGROUND: Three trials demonstrated recently that a long detection window reduces implantable cardioverter-defibrillator (ICD) therapy in primary prevention patients. Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients III (ADVANCE III) was the only trial that enrolled both primary and secondary prevention patients. METHODS AND RESULTS: Of the 1902 patients enrolled in the ADVANCE III trial, 477 received a defibrillator for secondary prevention; 248 patients were randomly assigned to a long detection setting (30 of 40 intervals) and 229 to the nominal setting (18 of 24 intervals) for ventricular arrhythmias with cycle length ≤ 320 ms. Eight-five percent of patients were men, with a mean age of 65 ± 12 years, a previous history of ventricular fibrillation in 37% of the cases, and a mean ejection fraction of 38 ± 13%. The ICD device mix was 37% single chamber, 47% dual chamber, and 16% triple chamber. Over a median period of 12 months, the long detection period was associated with a 25% reduction in the number of overall therapies (115.6 versus 86.8 per 100 patient-years; incidence rate ratio, 0.75; 95% confidence interval, 0.61-0.93; P=0.008) and a 34% reduction in the number of shocks (rate per 100 patient-years, 51.2 versus 38.1; incidence rate ratio, 0.66; 95% confidence interval, 0.48-0.89; P=0.007). Appropriate therapies (89.7 versus 67.7; incidence rate ratio, 0.77; 95% confidence interval, 0.60-0.97; P=0.029) and appropriate shocks (37.1 versus 28.1; incidence rate ratio, 0.64; 95% confidence interval, 0.45-0.93; P=0.018) were also reduced. CONCLUSIONS: ADVANCE III is the first randomized trial to assess a long detection window setting in ICDs in both primary and secondary prevention populations and demonstrates a reduction of overall therapies and shocks in the subgroup of secondary prevention patients. These data suggest that even the secondary prevention population may benefit from programming that combines a long detection period with antitachycardia pacing during charging. CLINICAL TRIAL REGISTRATION URL: http://www/clinicaltrials.gov. Unique identifier: NCT00617175.

Shock Reduction With Multiple Bursts of Antitachycardia Pacing Therapies to Treat Fast Ventricular Tachyarrhythmias in Patients With Implantable Cardioverter Defibrillators: A Multicenter Study.

INTRODUCTION: An empirical sequence of burst antitachycardia pacing (ATP) is effective in terminating fast ventricular tachycardias (FVT) in patients with implantable cardioverter-defibrillators (ICDs). We aimed to determine whether multiple ATP bursts for termination of FVT results in shock reduction compared to a single ATP burst. METHODS AND RESULTS: We analyzed data from the Umbrella trial, a multicenter prospective observational study of ICD patients followed by the CareLink Monitoring System. We compared the safety and effectiveness of a single ATP burst (Group 1) with a strategy of successive ATP sequences (Group 2) for termination of FVT episodes (cycle lengths 250-320 milliseconds) before shock therapy. Over a mean follow-up of 35 months, a total of 650 FVT episodes were detected in 154 patients (mean cycle length: 299 ± 18 milliseconds). Effectiveness of the first burst ATP in Group 1 was 73% and shocks were required in 27% of episodes. Effectiveness of the first burst ATP in Group 2 was 77%, and this increased to 91% with the third or successive ATP bursts. Shocks were required in 9% of episodes in group 2, representing a 67% reduction in the need of high-energy shocks. Median duration of FVT episodes and mortality in both groups were similar. Multivariate analysis indicated that programming multiple ATP bursts (OR 3.4, 95%CI 1.7-6.8, P = 0.001) was an independent predictor of ATP effectiveness. CONCLUSION: This study provides first evidence that a strategy of multiple burst ATP sequences for termination of FVT episodes leads to a clinically meaningful reduction in the need for shocks.

The clinical impact of untreated slow ventricular tachycardia in patients carrying implantable cardiac defibrillators.

INTRODUCTION: The clinical impact of slow ventricular tachycardia (VT), occurring in patients carrying implantable cardiac defibrillators (ICD), is still under debate. METHODS AND RESULTS: From the UMBRELLA registry (multicenter, observational, and prospective study on patients with ICD), 659 episodes of slow VT were observed in 97 patients. Untreated slow VT (n = 93) had longer duration (23.7 min, CI95%: 10-39), compared with episodes treated effectively by anti-tachycardia pacing (ATP; n = 527; 0.32 min, IC95%: 0.22-0, 48) or shock (n = 39; 1 min, CI95%: 0.8-1.2). Despite of longer duration, the time to the first contact with the medical services was similar to those episodes treated by ATP (50 days [CI95%: 45-55] vs. 41 days [CI95%: 39-44]). However, both were significantly longer than the time observed in episodes treated with shock (10 days, CI95%: 6-15). This tendency was maintained with successive interrogations of the device (2nd and 3rd). There were no significant differences in mortality during follow-up (48 ± 16 months), neither other adverse outcomes, between patients who presented untreated slow TV and those who did not (log-rank p = 0.28). In a Cox regression analysis, the variable "presenting untreated episodes of slow VT" was not able to predict mortality. However, being in sinus rhythm (vs. atrial fibrillation, OR: 0.31, p = 0.009), narrower QRS (OR: 1.036, p = 0.037) and diabetes (OR 4.673, p = 0.049) appropriately predict survival. CONCLUSIONS: Untreated slow VT does not significantly worsen patient prognosis. Our results support the limitation of therapies to ATP only, thus avoiding therapies that have been associated with increased risk of morbidity and mortality.

Predictors of adoption and impact of evidence-based programming on the incidence of implantable cardioverter-defibrillator therapies.

INTRODUCTION AND OBJECTIVES: The ADVANCE III trial showed that a delayed-detection strategy reduces implantable cardioverter-defibrillator (ICD) therapies. Here, we describe the adherence to and predictors of ADVANCE adoption and compare ICD therapy rates between patients with and without ADVANCE programming. METHODS: This observational retrospective study analyzed patients implanted with Medtronic ICDs included from 2005 to 2016 in a Spanish national multicenter registry (UMBRELLA database; ClinicalTrials.gov, NCT01561144). Changes in ADVANCE programming adoption were described in relation to a) publication of the ADVANCE trial, b) implementation of an "ADVANCE awareness" campaign, and c) publication of an expert consensus statement. Multivariate logistic regression identified predictors of adoption. Therapy incidence rates were compared between groups by estimating the adjusted incidence rate ratio (aIRR) using negative binomial regression. RESULTS: A total of 3528 patients were included. An ADVANCE strategy was used in 20% overall and in 44% at the end of the study. ADVANCE III adoption increased after trial publication, with less growth after an "ADVANCE awareness" campaign and after expert consensus statement publication. Predictors of ADVANCE adoption were as follows: ICD device with a nominal number of intervals to detect 30/40 (aOR, 4.4; 95%CI, 3.5-5.4), implantation by an electrophysiologist (aOR, 1.7; 95%CI, 1.4-2.2), and secondary prevention (aOR, 3.2; 95%CI, 2.6-3.9). Dual-chamber ICDs (aOR, 0.6; 95%CI, 0.5-0.8) and cardiac resynchronization-defibrillators (aOR, 0.5; 95%CI, 0.4-0.7) were associated with lower adoption. ADVANCE programming was associated with reduced total therapy burden (aIRR, 0.77; 95%CI, 0.69-0.86) and fewer inappropriate shocks (aIRR, 0.66; 95%CI, 0.52-0.85). CONCLUSIONS: ADVANCE adoption remains modest and can be improved through evidence-driven selection of nominal ICD settings. ADVANCE programming is associated with reduced therapy rates in real-world ICD recipients.

Long-Term Outcomes Among a Nationwide Cohort of Patients Using an Implantable Cardioverter-Defibrillator: UMBRELLA Study Final Results.

Background Large-scale studies describing modern populations using an implantable cardioverter-defibrillator (ICD) are lacking. We aimed to analyze the incidence of arrhythmia, device interventions, and mortality in a broad spectrum of real-world ICD patients with different heart disorders. Methods and Results The UMBRELLA study is a prospective, multicenter, nationwide study of contemporary patients using an ICD followed up by remote monitoring, with a blinded review of arrhythmic episodes. From November 2005 to November 2017, 4296 patients were followed up. After 46.6±27.3 months, 16 067 episodes of sustained ventricular arrhythmia occurred in 1344 patients (31.3%). Appropriate ICD therapy occurred in 27.3% of study population. Patients with ischemic cardiomyopathy (hazard ratio [HR], 1.51; 95% CI, 1.29-1.78), dilated cardiomyopathy (HR, 1.28; 95% CI, 1.07-1.53), and valvular heart disease (HR, 1.94; 95% CI, 1.43-2.62) exhibited a higher risk of appropriate ICD therapies, whereas patients with hypertrophic cardiomyopathy (HR, 0.72; 95% CI, 0.54-0.96) and Brugada syndrome (HR, 0.25; 95% CI, 0.14-0.45) showed a lower risk. All-cause death was 13.4% at follow-up. Ischemic cardiomyopathy (HR, 3.09; 95% CI, 2.58-5.90), dilated cardiomyopathy (HR, 3.33; 95% CI, 2.18-5.10), and valvular heart disease (HR, 3.97; 95% CI, 2.25-6.99) had the worst prognoses. Delayed high-rate detection was enabled in 39.7% of patients, and single-zone programming occurred in 52.6% of primary prevention patients. Both parameters correlated with lower risk of first appropriate ICD therapy, with no excess risk of mortality. The rate of inappropriate shocks at follow-up was low (6%) and did not differ among type of ICD but was lower in SmartShock-capable devices. Conclusions Irrespective of the cause, contemporary ICD patients with heart failure-related disorders had a similar risk of ICD life-saving interventions and death. Current ICD programming recommendations still need to be implemented. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NTC01561144.

Sex-Specific Ventricular Arrhythmias and Mortality in Cardiac Resynchronization Therapy Recipients.

OBJECTIVES: The study goal was to examine whether there are sex-related differences in the incidence of ventricular arrhythmias and mortality in CRT-defibrillator (CRT-D) recipients. BACKGROUND: Few studies have evaluated sex-related benefits of cardiac resynchronization therapy (CRT). Moreover, data on sex-related differences in the occurrence of ventricular tachyarrhythmias in this population are limited. METHODS: A multicenter retrospective study was conducted in 460 patients (355 male subjects and 105 female subjects) from the UMBRELLA (Incidence of Arrhythmia in Spanish Population With a Medtronic Implantable Cardiac Defibrillator Implant) national registry. Patients were followed up through remote monitoring after the first implantation of a CRT-D during a median follow-up of 2.2 ± 1.0 years. Sex differences were analyzed in terms of ventricular arrhythmia-treated incidence and death during the follow-up period, with a particular focus on primary prevention patients. RESULTS: Baseline New York Heart Association functional class was worse in women compared with that in men (67.0% of women in New York Heart Association functional class III vs. 49.7% of men; p = 0.003), whereas women had less ischemic cardiac disease (20.8% vs. 41.7%; p < 0.001). Female sex was an independent predictor of ventricular arrhythmias (hazard ratio: 0.40; 95% confidence interval: 0.19 to 0.86; p = 0.020), as well as left ventricular ejection fraction and nonischemic cardiomyopathy. Mortality in women was one-half that of men, although events were scarce and without significant differences (2.9% vs. 5.6%; p = 0.25). CONCLUSIONS: Women with left bundle branch block and implanted CRT have a lower rate of ventricular tachyarrhythmias than men. All-cause mortality in patients is, at least, similar between female and male subjects.

BIVentricular versus right ventricular antitachycardia pacing to terminate ventricular tachyarrhythmias in patients receiving cardiac resynchronization therapy: the ADVANCE CRT-D Trial.

BACKGROUND: This multicenter, prospective, randomized, controlled, parallel trial compares the efficacy of biventricular (BIV) versus right ventricular (RV) antitachycardia pacing (ATP) in terminating all kinds of ventricular tachycardia (VT). METHODS: Five hundred twenty-six patients implanted with a cardiac resynchronization therapy defibrillator (CRT-D) device were enrolled and randomized 1:1 to either BIV (266) or RV (260) ATP (single burst 8 pulse, 88% coupling interval) and were followed up for 12 months. RESULTS: During 12 months' follow-up, 1,077 ventricular episodes in 180 patients were detected and classified: 634 true VTs divided into 69 ventricular fibrillation (VF) (11%), 202 fast ventricular tachycardia (FVT) (32%), and 363 VT (57%). A comparable first ATP efficacy (BIV 65% vs RV 68%, P = .59) was observed in FVT + VT, in VT zone (BIV 62% vs RV 71%, P = .25), and in FVT zone (BIV 71% vs RV 61%, P = .34). A trend toward lower accelerations during ATP applied to FVT was observed in the BIV group (3.5% BIV vs 10.2% RV, P = .163). No syncope/presyncope occurred during ATP for FVT in the BIV group versus 4 events (3.2%) in the RV group (P = .016). biventricular ATP was more effective in treating FVT in coronary artery disease (CAD) patients (P = .032), whereas both modalities presented similar efficacy in patients with non-CAD etiology (P = .549). CONCLUSIONS: Antitachycardia pacing is effective in patients implanted with a CRT-D device. No significant differences in efficacy emerged between BIV- and RV-delivered ATP in the general population, whereas BIV ATP seems to present a safer profile in ischemic patients.

Prognostic role of NYHA class in heart failure patients undergoing primary prevention ICD therapy.

AIMS: Concerns about the prognostic value of NYHA functional class (FC) in heart failure (HF) patients carrying a prophylactic implantable cardioverter defibrillator (ICD) are still present. We aimed to compare whether mortality and arrhythmic risk were different, in a cohort of HF patients undergoing ICD-only implant, according to their FC. METHODS AND RESULTS: HF patients with left ventricle ejection fraction (LVEF) ≤35%, undergoing first prophylactic ICD-only implant were collected from a multicentre nationwide registry (2006-2015). Six hundred and twenty-one patients were identified (101 patients in NYHA I; 411 in NYHA II; 109 in NYHA III). After a mean follow-up of 4.4 years (±2.1), 126 patients died (20.3%). All-cause mortality risk was higher in symptomatic patients: 13.9% in NYHA I patients, 18.3% in NYHA II patients (HR: 1.8, 95% CI 1.1-3.2), and 32.9% in NYHA III patients (HR: 3.9, 95% CI 2.1-7.3). Seventy-eight out of all deaths were due to cardiovascular causes (12.6%). Cardiovascular mortality risk was also higher in symptomatic patients: 6.9% in NYHA I patients, 11% in NYHA II patients (HR: 2.2, 95% CI 1.1-4.9), and 23.9% in NYHA III (HR: 5.5, 95% CI 2.4-12.7). One hundred and seventeen patients received a first appropriate ICD therapy (19.4%). Arrhythmia free survival did not differ among study groups [20.8% in NYHA I patients, 18.7% in NYHA II (HR: 1.1, 95% CI 0.6-1.7) and 20.8% in NYHA III patients (HR: 1.3, 95% CI 0.7-2.5)]. NYHA class independently predicted cardiovascular mortality (NYHA III vs. NYHA I: HR, 4.7; 95% CI, 1.7-12.8, P = 0.002; NYHA II vs. NYHA I: HR, 2.1, 95% CI, 1.0-5.6, P = 0.05) but not all-cause death (NYHA III vs. NYHA I: HR: 1.8, 95% CI 0.8-3.9, P = 0.11; NYHA II vs. NYHA I: HR, 1.1, 95% CI 0.6-2.2, P = 0.71;). Atrial fibrillation, chronic kidney disease, and diabetes emerged as predictors of both all-cause death [(HR: 1.8, 95% CI 1.2-2.8, P = 0.005), (HR: 2.2, 95% CI 1.4-3.4, P < 0.001), (HR: 2.0, 95% CI 1.3-3.1, P = 0.001), respectively] and cardiovascular mortality [(HR: 1.8, 95% CI 1.1-3.1, P = 0.02), (HR: 3.1, 95% CI 1.8-5.4, P < 0.001), (HR: 1.7, 95% CI 1.1-3, P = 0.032), respectively]. CONCLUSIONS: Mortality in HF patients undergoing prophylactic ICD implantation was higher in symptomatic patients. NYHA functional class along with other comorbidities might be helpful to identify a subgroup of ICD carriers with poorer prognosis and higher risk of cardiovascular death.

Sex differences in implantable cardiac defibrillator therapy according to arrhythmia detection times.

OBJECTIVE: In implantable cardiac defibrillators (ICDs), long-detection times safely reduce unnecessary and inappropriate therapies. We aimed to evaluate ICD treatment of ventricular arrhythmias in women, compared with men, also taking into account ICD detection. METHODS: The Advance III trial randomised patients implanted with an ICD for primary or secondary prevention in two arms-long and nominal ventricular arrhythmias detection times before therapy delivering (number of intervals needed to detect (NID) 30/40 and 18/24, respectively). The main endpoint of this post hoc analysis was the incidence of ICD therapies evaluated through Kaplan-Meier method and univariate Cox regression models. RESULTS: Overall, 1902 patients (304 women, 65±11 years) were randomised. Women showed a lower risk of ICD therapy (HR 0.63, 95% CI 0.43 to 0.93, p=0.022); this difference was observed only in the long-detection arm (HR 0.37, p=0.013) and not in the short detection arm (HR 0.82, p=0.414). No significant sex differences were observed concerning inappropriate therapies and mortality rate. Long-detection settings significantly reduced overall ICD therapies and appropriate ICD therapies, both in women (overall HR 0.31, p=0.007; appropriate HR 0.33, p=0.033) and in men (overall HR 0.69, p=0.006; appropriate HR 0.73, p=0.048). CONCLUSIONS: In patients with ICDs, the strategy of setting a long-detection time to treat ventricular arrhythmias (NID 30/40) reduces overall delivered therapies, both in women and men, when compared with nominal setting (NID 18/24). The reduction was significantly higher in women. Overall, women were less likely to experience ICD therapies than men; this result was only observed in the long-detection arm. CLINICAL TRIAL REGISTRATION: NCT00617175.

Survival and arrhythmic risk among ischemic and non-ischemic heart failure patients with prophylactic implantable cardioverter defibrillator only therapy: A propensity score-matched analysis.

BACKGROUND: Concerns about the efficacy of prophylactic ICD in non-ischemic cardiomyopathy (NICM) heart failure (HF) patients are still present. We aimed to assess whether survival and arrhythmic risk were different among ischemic cardiomyopathy (ICM) and NICM ICD-only patients, along with specific predictors for mortality. METHODS: HF patients undergoing ICD-only implant were extracted from the nationwide multicenter UMBRELLA registry. Arrhythmic events were collected by remote monitoring and reviewed by a committee of experts. RESULTS: 782 patients (556 ICM; 226 NICM) were recruited: mean ejection fraction of 26.6%; 83.4% in NYHA class II-III; mean QRS duration of 108.9 ms (only 14.9% with QRS > 130 ms). After 4.35 years of mean follow-up, all-cause mortality rate was 4.2%/year. In propensity-score (PS) analysis no survival differences between ICM and NICM subgroups appeared (mortality rates: 19.4% vs. 20%, p = 0.375). Age (hazard ratio [HR] = 1.02, p = 0.009), diabetes (HR = 2.61, p ≤ 0.001), chronic obstructive pulmonary disease (HR = 2.13, p = 0.002), and previous HF (HR = 2.28, p = 0.027) correlated with increased mortality for the entire population, however atrial fibrillation (AF) (HR = 2.68, p = 0.002) and chronic kidney disease (HR = 3.74, p ≤ 0.001) emerged as specific predictors in NICM patients. At follow-up, 134 patients (17.1%) were delivered a first appropriate ICD therapy (5.1%/year) without significant differences between ICM and NICM patients in the PS analysis (17.6% vs. 15.8%, p = 0.968). ICD shocks were associated with a higher mortality (HR = 2.88, p < 0.001) but longer detection windows (HR = 0.57, p = 0.042) correlated with fewer appropriate therapies. CONCLUSIONS: Mortality and arrhythmia free survival is similar among ICM and NICM HF patients undergoing ICD-only implant for primary prevention strategy.