Response rate in cardiac resynchronization therapy patients implanted with a left ventricular quadripolar lead and the MultiPoint™ pacing feature early activated. QUARTO III.

BACKGROUND: Although cardiac resynchronization therapy (CRT) is beneficial in most heart failure patients, up to 40% do not respond to CRT. It has been suggested that multipoint left ventricle pacing (MPP) would increase the response rate. AIM: To assess the CRT response rate at 6 months in patients implanted with a CRT device with the MPP feature activated early after the implant. METHODS: This was a multicentre, prospective, open-label and non-randomized study. The primary endpoint was response to biventricular pacing defined as >15% relative reduction in left ventricular end-systolic volume (LVESV) comparing echocardiography measurements performed at baseline and 6 months by a core laboratory. Among secondary endpoints the combined endpoint of mortality or all-cause hospitalizations was evaluated. Primary study endpoint and clinical outcomes were compared to a Quarto II control cohort. RESULTS: Totally, 105 patients were included. The response rate was 64.6% (97.5% lower confidence bound 53%). Mean relative reduction in LVESV was 25.3%, and mean absolute increase in LVEF was 9.4%. The subjects with device programmed using anatomical approach showed a trend towards higher responder rate than those using the electrical approach (72% vs. 61.1%, p = 0.32). Finally, the combined incidence of mortality and or all-cause hospitalizations at 6 month was 12.4%. CONCLUSIONS: Early activation of MPP was not associated to an advantage increasing echocardiography responders to CRT at 6 months of follow-up. Nevertheless, patients programmed using widest pacing cathodes had a numerically higher responder rate. Finally, early activation of MPP was associated to a low incidence of clinical endpoints at 6 months of follow-up.

Distinct spectral dynamics of implanted cardiac defibrillator signals in spontaneous termination of polymorphic ventricular tachycardia and fibrillation in patients with electrical and structural diseases.

AIMS: To determine the spectral dynamics of early spontaneous polymorphic ventricular tachycardia and ventricular fibrillation (PVT/VF) in humans. METHODS AND RESULTS: Fifty-eight self-terminated and 173 shock-terminated episodes of spontaneously initiated PVT/VF recorded by Medtronic implanted cardiac defibrillators (ICDs) in 87 patients with various cardiac pathologies were analyzed by short fast Fourier transform of shifting segments to determine the dynamics of dominant frequency (DF) and regularity index (RI). The progression in the intensity of DF and RI accumulations further quantified the time course of spectral characteristics of the episodes. Episodes of self-terminated PVT/VF lasted 8.6 s [95% confidence interval (CI): 8.1-9.1] and shock-terminated lasted 13.9 s (13.6-14.3) (P < 0.001). Recordings from patients with primarily electrical pathologies displayed higher DF and RI values than those from patients with primarily structural pathologies (P < 0.05) independently of ventricular function or antiarrhythmic drug therapy. Regardless of the underlying pathology, the average DF and RI intensities were lower in self-terminated than shock-terminated episodes [DF: 3.67 (4.04-4.58) vs. 4.32 (3.46-3.93) Hz, P < 0.001; RI: 0.53 (0.48-0.56) vs. 0.63 (0.60-0.65), P < 0.001]. In a multivariate analysis controlled by the type of pathology and clinical variables, regularity remained an independent predictor of self-termination [hazard ratio: 0.954 (0.928-0.980)]. Receiver operating characteristic (ROC) curve analysis of DF and RI intensities demonstrated increased predictability for self-termination in time with 95% CI above the 0.5 cut-off limit at about t = 8.6 s and t = 6.95 s, respectively. CONCLUSION: Consistent with the notion that fast organized sources maintain PVT/VF in humans, reduction of frequency and regularity correlates with early self-termination. Our findings might help generate ICD methods aiming to reduce inappropriate shock deliveries.

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.

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.

Impact of dynamic physical exercise on high-risk definite arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiomyopathy characterized by ventricular arrhythmias and heart failure. The variable phenotype suggesting that determined environmental factors may have an influence. The aim of our study was to discover the impact of the dynamic physical activity on patients with high-risk definite ARVC/D. METHODS AND RESULTS: Collection of data on physical activity at the time of diagnosis was conducted at an in-person clinical interview. The intensity of the activity was classified in accordance with the mean frequency of weekly physical exercise sessions in the 10 years before diagnosis and into the following three groups of dynamic activity: high/competitive (>3 h/wk), moderate (1 to 3 h) and minimal/inactive (<1 h). Seventeen patients practiced high dynamic physical activities. The intensity of dynamic activity was classified into three groups: 8 of high intensity, 9 moderate, and 19 inactive. The first major arrhythmic event and occurrence of severe right ventricular dysfunction were earlier in the high-intensity exercise group, followed by the moderate intensity group and at a later age in the low-intensity/inactive group. CONCLUSIONS: Dynamic exercise could be directly associated with the severity of the phenotype in relation to the precocity of major ventricular arrhythmic events and right ventricular systolic dysfunction in patients with high-risk definite ARVC/D.

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.

Small-Caliber Lead Failure After Generator Exchange.

INTRODUCTION AND OBJECTIVES: The Sprint Fidelis defibrillator lead (Medtronic) was recalled in 2007 due to an increased risk of failure. The generator exchange (GE) procedure has been associated with the development of Fidelis lead dysfunction. The aim of this study was to compare the rate of dysfunction between Sprint Fidelis and other defibrillator leads during the first year after GE. METHODS: A multicenter retrospective study involving patients from the UMBRELLA database who underwent GE with previous normal lead function and minimum follow-up of 1 year after the procedure was performed. The incidence of lead dysfunction was determined via remote monitoring and defined as pacing impedance > 1,500 ohm, high-voltage impedance > 100 ohm, R wave sensing under 2 mV, or the presence of VT/VF episodes classified as noise. RESULTS: A total of 531 patients were included (114 Fidelis). In the first year after GE, the total incidence of lead dysfunction was 3.6%. No significant differences were found between Fidelis and the others in survival analysis (3.5% vs. 3.6%, respectively, log-rank 0.002, P = 0.962). CONCLUSIONS: According to our results, the preventive removal/replacement of the Sprint Fidelis leads with normal function until GE is not a recommended practice since the rate of dysfunction after the procedure in this subgroup is no different compared with other defibrillator leads.

Comparison of the new risk prediction model (HCM Risk-SCD) and classic risk factors for sudden death in patients with hypertrophic cardiomyopathy and defibrillator.

AIMS: Hypertrophic cardiomyopathy is one of the main causes of sudden death in young people. Recent clinical practice guidelines include a risk prediction model for sudden death (HCM Risk-SCD), which facilitates the decision of whether to implant a defibrillator. The aim of our study was to ascertain the percentage of events in our series of primary prevention implantable cardioverter-defibrillator recipients with hypertrophic cardiomyopathy and whether HCM Risk-SCD predicts the onset of arrhythmic events. METHODS AND RESULTS: This was an observational, retrospective cohort study, which included 48 primary prevention defibrillator recipient patients with HCM. We compiled their demographic and clinical characteristics, estimated 5-year risk using HCM Risk-SCD, and collected the documentation on arrhythmias during follow-up. The majority was male (66.7%) and mean age at implantation was 44.44 ± 14.46 years. Non-sustained ventricular tachycardia was the most prevalent risk factor (66.67%), followed by a family history of sudden death (47.92%). Mean HCM Risk-SCD was 6.15 ± 5.01%. HCM Risk-SCD was the only factor independently associated with the onset of ventricular tachyarrhythmia, above any other classic risk factor or association [odds ratio = 1.46 (95% confidence interval 1.051-2.013); P = 0.02]. None of the 11 patients estimated as low risk using HCM Risk-SCD suffered any appropriate events (P < 0.05). CONCLUSIONS: During an average follow-up of 4 years, 16.67% presented appropriate events (4.16%/year). HCM Risk-SCD predicted the onset of events more suitably than classic risk factors.

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.

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.

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.

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.

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.

Serum levels of interleukin-2 predict the recurrence of atrial fibrillation after pulmonary vein ablation.

AIMS: Interleukin-2 has a significant antitumor activity in some types of cancer, and has been associated with the development of atrial fibrillation (AF). In addition, IL-2 serum levels in recent onset AF have been related with pharmaceutical cardioversion outcomes. We evaluated the hypothesis that a relationship exists between inflammation and the outcome of catheter ablation of AF. METHODS: We studied 44 patients with paroxysmal AF who underwent catheter ablation. Patients with structural heart disease, coronary artery or valve disease, active inflammatory disease, known or suspected neoplasm, endocrinopathies, or exposure to anti-inflammatory drugs were excluded. All study participants underwent evaluation with a standardized protocol, including echocardiography, and cytokine levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumour necrosis factor-alpha, and gamma-interferon determination before procedure. Clinical and electrocardiographic follow-up were performed with Holter-ECG at 3, 6 and 12months in order to know if sinus rhythm was maintained. RESULTS: After catheter ablation of the 44 patients included (53±10years, 27.3% female), all patients returned to sinus rhythm. During the first year of follow-up seven patients (15.9%) experienced recurrence of AF. The demographics, clinical and echocardiographic features, and pharmacological treatments of these patients were similar to those who maintained sinus rhythm. The only independent factor predictive of recurrence of AF was an elevated level of IL-2 (OR 1.18, 95% CI 1.12-1.38). CONCLUSIONS: High serum levels of interleukin-2, a pro-inflammatory non-vascular cytokine, are associated with the recurrence of AF in patients undergoing catheter ablation.

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.

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.

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.

Combined resynchronization therapy and automatic defibrillator in advanced non-ischaemic heart failure: the importance of QRS width.

AIMS: The combined use of an automatic defibrillator in resynchronization therapy for primary prevention in patients with idiopathic dilated cardiomyopathy is controversial. METHODS AND RESULTS: We assessed a series of 46 patients (61 +/- 10 years, 64% male) with idiopathic dilated cardiomyopathy undergoing resynchronization therapy combined with a defibrillator in primary prevention and the potential relationship between baseline characteristics and the onset of ventricular arrhythmic events. Of the 46 patients included, eight (17%) presented episodes of ventricular tachycardia/fibrillation during follow-up (19 +/- 12 months). There were no baseline differences among these patients, except the proportion of males (57.9 vs. 100%, P = 0.02) and QRS width (162 +/- 24 vs. 189 +/- 26 ms, P = 0.008), which was the only independent predictor of arrhythmic events (OR 1.42, 95% CI 1.12-1.68; P = 0.03). CONCLUSION: In patients with idiopathic dilated cardiomyopathy undergoing resynchronization therapy combined with a defibrillator, baseline QRS is an independent predictor of arrhythmic events.

Persistence of secondary mitral regurgitation and response to cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) improves survival and quality of life in advanced heart failure (HF). Although mitral regurgitation (MR) reduction has been reported, its presence has been associated with non-response to CRT. This study was undertaken to assess the potential role of significant mitral regurgitation (SMR) persistence after CRT on clinical outcome, major arrhythmic events, and echocardiographic response in the mid-long term. METHODS AND RESULTS: Seventy-six patients (28.9% women, 63 +/- 11 years) with dilated cardiomyopathy in advanced HF were included. SMR, defined as regurgitant orifice area > or =0.20 cm(2), was assessed at baseline and its evolution 6 months after CRT. Clinical outcome (cardiovascular death/HF readmission), major arrhythmic events, and echocardiographic response (reverse remodelling) were recorded on follow-up. Thirty-two patients (42.1%) presented baseline SMR, becoming non-significant in 11 of the 32 patients (34.3%) 6 months after CRT. Its persistence was associated with higher rates of clinical events (46.4 vs. 18.7%, P = 0.011), arrhythmic events (35.7 vs. 14.5%, P = 0.034), and less reverse remodelling (28.5 vs. 83.3%, P < 0.001). CONCLUSION: CRT can reduce moderate or severe baseline MR to non-significant in one-third of patients. However, its persistence was associated with worse clinical evolution, greater incidence of arrhythmic events, and less reverse remodelling.

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.