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.

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.

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.

Single-brand dual-chamber discriminators to prevent inappropriate shocks in patients implanted with prophylactic implantable cardioverter defibrillators: a propensity-weighted comparison of single- and dual-chamber devices.

PURPOSE: Comparisons of the efficacy of dual- vs. single-chamber implantable cardioverter defibrillators (ICDs) in preventing inappropriate shocks have had contradictory results. We investigated whether dual-chamber devices have a lower risk of inappropriate shocks and the specific role of supraventricular tachycardia (SVT) discriminators. METHODS: All heart failure (HF) patients without an indication for pacing and implanted with a prophylactic ICD were recruited from the nationwide multicenter UMBRELLA registry. Arrhythmic events were collected by remote monitoring and reviewed by a committee of experts. RESULTS: Among 782 patients, single-chamber ICDs were implanted in 537 (68.7%) and dual-chamber devices in 245 (31.3%). During a mean follow-up of 52.2 ± 24.5 months, 109 inappropriate shocks were delivered in 49 patients (6.2%). In the propensity-score-matched analysis, dual-chamber ICDs were related to lower rates of inappropriate shocks as compared to single-chamber devices (0.9% vs. 11.8%, p = < 0.001, log-rank test). In multivariable Cox proportional analysis, independent predictors of inappropriate shock were history of atrial fibrillation (hazard ratio (HR) = 2.78, CI 1.37-5.64, p = 0.004), chronic kidney disease (HR = 6.15, CI 2.82-13.53, p < 0.001), and non-ischemic cardiomyopathy (HR = 2.84, CI 1.54-5.23, p = 0.001). Among ICD settings, PR logic was the only discriminator independently related to a reduced risk of inappropriate shocks (HR = 0.18, CI 0.06-0.48, p = 0.001), along with an SVT limit enabled over 200 bpm (HR = 0.24, CI 0.11-0.51, p < 0.001). CONCLUSIONS: In this nationwide cohort of primary prevention ICD-only patients, dual-chamber devices were related to lower risk of inappropriate shocks compared to single-chamber ICDs. Besides, PR logic and SVT limit > 200 bpm emerged as protective factors.

Shock Reduction With Antitachycardia Pacing Before and During Charging for Fast Ventricular Tachycardias in Patients With Implantable Defibrillators.

INTRODUCTION AND OBJECTIVES: Fast ventricular tachycardias in the ventricular fibrillation zone in patients with an implantable cardioverter-defibrillator are susceptible to antitachycardia pacing (ATP) termination. Some manufacturers allow programming 2 ATP bursts: before charging (BC) and during (DC) charging. The aim of this study was to describe the safety and effectiveness of ATP BC and DC for fast ventricular tachycardias in the ventricular fibrillation zone in patients with an implantable cardioverter-defibrillator in daily clinical practice. METHODS: Data proceeded from the multicenter UMBRELLA trial, including implantable cardioverter-defibrillator patients followed up by the CareLink monitoring system. Fast ventricular tachycardias in the ventricular fibrillation zone until a cycle length of 200ms with ATP BC and/or ATP DC were included. RESULTS: We reviewed 542 episodes in 240 patients. Two ATP bursts (BC/DC) were programmed in 291 episodes (53.7%, 87 patients), while 251 episodes (46.3%, 153 patients) had 1 ATP burst only DC. The number of episodes terminated by 1 ATP DC was 139, representing 55.4% effectiveness (generalized estimating equation-adjusted 60.4%). There were 256 episodes terminated by 1 or 2 ATP (BC/DC), representing 88% effectiveness (generalized estimating equation-adjusted 79.3%); the OR for ATP effectiveness BC/DC vs DC was 2.5, 95%CI, 1.5-4.1; P <.001. Shocked episodes were 112 (45%) for ATP DC vs 35 (12%) for ATP BC/DC, representing an absolute reduction of 73%. The mean shocked episode duration was 16seconds for ATP DC vs 19seconds for ATP BC/DC (P=.07). CONCLUSIONS: The ATP DC in the ventricular fibrillation zone for fast ventricular tachycardia is moderately effective. Adding an ATP burst BC increases the overall effectiveness, reduces the need for shocks, and does not prolong episode duration.

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.

Long Detection Programming in Single-Chamber Defibrillators Reduces Unnecessary Therapies and Mortality: The ADVANCE III Trial.

OBJECTIVES: This study sought to evaluate the effects of programming a long detection in single-chamber (VVI) implantable cardioverter-defibrillators (ICDs) in the multicenter prospective ADVANCE III (Avoid DeliVering TherApies for Non-sustained Arrhythmias in ICD PatiEnts III) trial. BACKGROUND: Programming strategies may reduce unnecessary ICD shocks and their adverse effects but to date have been described only for dual-chamber ICDs. METHODS: A total of 545 subjects (85% male; atrial fibrillation 25%, left ventricular ejection fraction 31%, ischemic etiology 68%, secondary prevention indications 32%) receiving a VVI ICD were randomized to long detection (30 of 40 intervals) or standard programming (18 of 24 intervals) based on device type, atrial fibrillation history, and indication. In both arms, antitachycardia pacing (ATP) therapy during charging was programmed for episodes with cycle length 320 to 200 ms and shock only for cycle length <200 ms. Wavelet and stability functions enabled. Therapies delivered were compared using a negative binomial regression model. RESULTS: A total of 267 patients were randomized to long detection and 278 to the control group. Median follow-up was 12 months. One hundred twelve therapies (shocks and ATP) occurred in the long detection arm versus 257 in the control arm, for a 48% reduction with 30 of 40 intervals (95% confidence interval [CI]: 0.36 to 0.76; p = 0.002). In the long detection arm, overall shocks were reduced by 40% compared to the control arm (48 vs. 24; 95% CI: 0.38 to 0.94; p = 0.026) and appropriate shocks by 51% (34 vs. 74; 95% CI: 0.26 to 0.94; p = 0.033). Syncopal events did not differ between arms, but survival improved in the long detection arm. CONCLUSIONS: Among patients implanted with a VVI ICD, programming with the long detection interval significantly reduced appropriate therapies, shocks, and all-cause mortality. (Avoid DeliVering TherApies for Non-sustained Arrhythmias in ICD PatiEnts III [ADVANCEIII]; NCT00617175).

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.

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.