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Aims: The HeartLogic algorithm combines multiple implantable defibrillator (ICD) sensor data and has proved to be a sensitive and timely predictor of impending heart failure (HF) decompensation in cardiac resynchronization therapy (CRT-D) patients. We evaluated the performance of this algorithm in non-CRT ICD patients and in the presence of co-morbidities., Methods and Results: The HeartLogic feature was activated in 568 ICD patients (410 with CRT-D) from 26 centres. The median follow-up was 26 months [25th-75th percentile: 16-37]. During follow-up, 97 hospitalizations were reported (53 cardiovascular) and 55 patients died. We recorded 1200 HeartLogic alerts in 370 patients. Overall, the time IN the alert state was 13% of the total observation period. The rate of cardiovascular hospitalizations or death was 0.48/patient-year (95% CI: 0.37-0.60) with the HeartLogic IN the alert state and 0.04/patient-year (95% CI: 0.03-0.05) OUT of the alert state, with an incidence rate ratio of 13.35 (95% CI: 8.83-20.51, P < 0.001). Among patient characteristics, atrial fibrillation (AF) on implantation (HR: 1.62, 95% CI: 1.27-2.07, P < 0.001) and chronic kidney disease (CKD) (HR: 1.53, 95% CI: 1.21-1.93, P < 0.001) independently predicted alerts. HeartLogic alerts were not associated with CRT-D versus ICD implantation (HR: 1.03, 95% CI: 0.82-1.30, P = 0.775). Comparisons of the clinical event rates in the IN alert state with those in the OUT of alert state yielded incidence rate ratios ranging from 9.72 to 14.54 (all P < 0.001) in all groups of patients stratified by: CRT-D/ICD, AF/non-AF, and CKD/non-CKD. After multivariate correction, the occurrence of alerts was associated with cardiovascular hospitalization or death (HR: 1.92, 95% CI: 1.05-3.51, P = 0.036)., Conclusions: The burden of HeartLogic alerts was similar between CRT-D and ICD patients, while patients with AF and CKD seemed more exposed to alerts. Nonetheless, the ability of the HeartLogic algorithm to identify periods of significantly increased risk of clinical events was confirmed, regardless of the type of device and the presence of AF or CKD., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The HeartLogic algorithm (Boston Scientific) has proved to be a sensitive and timely predictor of impending heart failure (HF) decompensation., Objective: The purpose of this study was to determine whether remotely monitored data from this algorithm could be used to identify patients at high risk for mortality., Methods: The algorithm combines implantable cardioverter-defibrillator (ICD)-measured accelerometer-based heart sounds, intrathoracic impedance, respiration rate, ratio of respiration rate to tidal volume, night heart rate, and patient activity into a single index. An alert is issued when the index crosses a programmable threshold. The feature was activated in 568 ICD patients from 26 centers., Results: During median follow-up of 26 months [25th-75th percentile 16-37], 1200 alerts were recorded in 370 patients (65%). Overall, the time IN-alert state was 13% of the total observation period (151/1159 years) and 20% of the follow-up period of the 370 patients with alerts. During follow-up, 55 patients died (46 in the group with alerts). The rate of death was 0.25 per patient-year (95% confidence interval [CI] 0.17-0.34) IN-alert state and 0.02 per patient-year (95% CI 0.01-0.03) OUT of the alert state, with an incidence rate ratio of 13.72 (95% CI 7.62-25.60; P <.001). After multivariate correction for baseline confounders (age, ischemic cardiomyopathy, kidney disease, atrial fibrillation), the IN-alert state remained significantly associated with the occurrence of death (hazard ratio 9.18; 95% CI 5.27-15.99; P <.001)., Conclusion: The HeartLogic algorithm provides an index that can be used to identify patients at higher risk for all-cause mortality. The index state identifies periods of significantly increased risk of death., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: The prediction of ventricular tachyarrhythmias among patients with implantable cardioverter defibrillators is difficult with available clinical tools. We sought to assess whether in patients with heart failure (HF) and reduced ejection fraction with defibrillators, physiological sensor-based HF status, as summarized by the HeartLogic index, could predict appropriate device therapies., Methods: Five hundred and sixty-eight consecutive HF patients with defibrillators (n = 158, 28%) or cardiac resynchronization therapy-defibrillators (n = 410, 72%) were included in this prospective observational multicenter analysis. The association of both HeartLogic index and its physiological components with defibrillator shocks and overall appropriate therapies was assessed in regression and time-dependent Cox models., Results: Over a follow-up of 25 (15-35) months, 122 (21%) patients received an appropriate device therapy (shock, n = 74, 13%), while the HeartLogic index crossed the threshold value (alert, HeartLogic ≥ 16) 1200 times (0.71 alerts/patient-year) in 370 (65%) subjects. The occurrence of ≥1 HeartLogic alert was significantly associated with both appropriate shocks (Hazard ratios [HR]: 2.44, 95% confidence interval [CI]: 1.49-3.97, p = .003), and any appropriate defibrillator therapies. In multivariable time-dependent Cox models, weekly IN-alert state was the strongest predictor of appropriate defibrillator shocks (HR: 2.94, 95% CI: 1.73-5.01, p < .001) and overall therapies. Compared with stable patients, patients with appropriate shocks had significantly higher values of HeartLogic index, third heart sound amplitude, and resting heart rate 30-60 days before device therapy., Conclusion: The HeartLogic index is an independent dynamic predictor of appropriate defibrillator therapies. The combined index and its individual physiological components change before the arrhythmic event occurs., (© 2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Aims: HeartLogic algorithm combines data from multiple implantable defibrillators (ICD)-based sensors to predict impending heart failure (HF) decompensation. A treatment protocol to manage algorithm alerts is not yet known, although decongestive treatment adjustments are the most frequent alert-triggered actions reported in clinical practice. We describe the implementation of HeartLogic for remote monitoring of HF patients, and we evaluate the approach to diuretic dosing and timing of the intervention in patients with device alerts., Methods: The algorithm was activated in 229 ICD patients at eight centers. The median follow-up was 17 months (25th-75th percentile: 11-24). Remote data reviews and patient phone contacts were undertaken at the time of HeartLogic alerts, to assess the patient's status and to prevent HF worsening. We analyzed alert-triggered augmented HF treatments, consisting of isolated increases in diuretics dosage., Results: We reported 242 alerts (0.8 alerts/patient-year) in 123 patients, 137 (56%) alerts triggered clinical actions to treat HF. The HeartLogic index decreased after the 56 actions consisting of diuretics increase. Specifically, alerts resolved more quickly when the increases in dosing of diuretics were early rather than late: 28 days versus 62 days, p < .001. The need of hospitalization for further treatments to resolve the alert condition was associated with higher HeartLogic index values on the day of the diuretics increase (odds ratio: 1.11, 95% CI: 1.02-1.20, p = .013) and with late interventions (odds ratio: 5.11, 95% CI: 1.09-24.48, p = .041). No complications were reported after drug adjustments., Conclusions: Decongestive treatment adjustments triggered by alerts seem safe and effective. The early use of decongestive treatment and the use of high doses of diuretics seem to be associated with more favorable outcomes., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: The HeartLogic algorithm combines multiple implantable cardioverter-defibrillator sensors to identify patients at risk of heart failure (HF) events. We sought to evaluate the risk stratification ability of this algorithm in clinical practice. We also analyzed the alert management strategies adopted in the study group and their association with the occurrence of HF events., Methods: The HeartLogic feature was activated in 366 implantable cardioverter-defibrillator and cardiac resynchronization therapy implantable cardioverter-defibrillator patients at 22 centers. The median follow-up was 11 months [25th-75th percentile: 6-16]. The HeartLogic algorithm calculates a daily HF index and identifies periods IN alert state on the basis of a configurable threshold., Results: The HeartLogic index crossed the threshold value 273 times (0.76 alerts/patient-year) in 150 patients. The time IN alert state was 11% of the total observation period. Patients experienced 36 HF hospitalizations, and 8 patients died of HF during the observation period. Thirty-five events were associated with the IN alert state (0.92 events/patient-year versus 0.03 events/patient-year in the OUT of alert state). The hazard ratio in the IN/OUT of alert state comparison was (hazard ratio, 24.53 [95% CI, 8.55-70.38], P <0.001), after adjustment for baseline clinical confounders. Alerts followed by clinical actions were associated with less HF events (hazard ratio, 0.37 [95% CI, 0.14-0.99], P =0.047). No differences in event rates were observed between in-office and remote alert management., Conclusions: This multiparametric algorithm identifies patients during periods of significantly increased risk of HF events. The rate of HF events seemed lower when clinical actions were undertaken in response to alerts. Extra in-office visits did not seem to be required to effectively manage HeartLogic alerts. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02275637.

Background: Current guidelines recommend avoiding apical left ventricular (LV) pacing for cardiac resynchronization therapy (CRT)., Aims: We investigated the feasibility of nonapical pacing with the current quadripolar LV lead technology., Methods: We analyzed consecutive patients who received CRT with an LV quadripolar lead. The post--implantation position of each electrode of the LV lead was designated as basal, mid, or apical. The pacing capture threshold (PCT) and phrenic nerve stimulation (PNS) threshold were assessed for each electrode., Results: We enrolled 168 patients. A total of 8 CRT defibrillators were from Biotronik (with Sentus OTW QP leads), 98 were from Boston Scientific (with 21 Acuity X4 Spiral and 77 Acuity X4 Straight leads), and 62 from St. Jude Medical (with Quartet leads). The median (interquartile range) number of electrodes at nonapical segments per patient was 3 (1-4) with Biotronik Sentus leads, 4 (3-4) with spiral -design Boston Scientific leads, 4 (3-4) with straight Boston Scientific leads, and 3 (3-4) with St. Jude Medical Quartet leads (P = 0.045). Three patients (38%) with Biotronik Sentus leads, 21 (100%) with spiral -design Boston Scientific leads, 69 (90%) with straight -design Boston Scientific leads, and 49 (79%) with St. Jude Medical Quartet leads (P <0.001) had at least 1 electrode located at nonapical segments linked with a PNS -PCT safety margin of more than 2 V. During the 6-month follow -up, PNS was detected in 4 patients and was eliminated with reprogramming. No significant changes in PCT were detected during follow -up., Conclusions: Quadripolar leads allowed nonapical pacing with acceptable electrical parameters in the majority of CRT recipients, although differences were found among the currently available devices.

Background: Multiple left ventricular pacing strategies have been suggested for improving response to cardiac resynchronization therapy (CRT). However, these programming strategies may sometimes entail accepting configurations with high pacing threshold and accelerated battery drain. We assessed the feasibility of predefined pacing programming protocols, and we evaluated their impact on device longevity and their cost-impact., Methods: We estimated battery longevity in 167 CRT-D patients based on measured pacing parameters according to multiple alternative programming strategies: single-site pacing associated with lowest threshold, non-apical location, longest interventricular delay, and pacing from two electrodes. To determine the economic impact of each programming strategy, we applied the results of a model-based cost analysis using a 15-year time horizon., Results: Selecting the electrode with the lowest threshold resulted in a median device longevity of 11.5 years. Non-apical pacing and interventricular delay maximization were feasible in most patients and were obtained at the price of a few months of battery life. Device longevity of > 10 years was preserved in 87% of cases of non-apical pacing and in 77% on pacing at the longest interventricular delay. The mean reduction in battery life when the second electrode was activated was 1.5 years. Single-site pacing strategies increased the therapy cost by 4-6%, and multi-site pacing by 12-13%, in comparison with the lowest-cost scenario., Conclusions: Modern CRT-D systems ensure effective pacing and allow multiple optimization strategies for maximizing service life or for enhancing effectiveness. Single- or multi-site pacing strategies can be implemented without compromising device service life and at an acceptable increase in therapy cost.

Background: The HeartLogic algorithm measures data from multiple implantable cardioverter-defibrillator-based sensors and combines them into a single index. The associated alert has proved to be a sensitive and timely predictor of impending heart failure (HF) decompensation., Hypothesis: We describe a multicenter experience of remote HF management by means of HeartLogic and appraise the value of an alert-based follow-up strategy., Methods: The alert was activated in 104 patients. All patients were followed up according to a standardized protocol that included remote data reviews and patient phone contacts every month and at the time of alerts. In-office examinations were performed every 6 months or when deemed necessary., Results: During a median follow-up of 13 (10-16) months, the overall number of HF hospitalizations was 16 (rate 0.15 hospitalizations/patient-year) and 100 alerts were reported in 53 patients. Sixty alerts were judged clinically meaningful, and were associated with multiple HF-related conditions. In 48 of the 60 alerts, the clinician was not previously aware of the condition. Of these 48 alerts, 43 triggered clinical actions. The rate of alerts judged nonclinically meaningful was 0.37/patient-year, and the rate of hospitalizations not associated with an alert was 0.05/patient-year. Centers performed remote follow-up assessments of 1113 scheduled monthly transmissions (10.3/patient-year) and 100 alerts (0.93/patient-year). Monthly remote data review allowed to detect 11 (1%) HF events requiring clinical actions (vs 43% actionable alerts, P < .001)., Conclusions: HeartLogic allowed relevant HF-related clinical conditions to be identified remotely and enabled effective clinical actions to be taken; the rates of unexplained alerts and undetected HF events were low. An alert-based management strategy seemed more efficient than a scheduled monthly remote follow-up scheme., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Background: Epicardial placement of the left ventricular (LV) lead via a video-assisted thoracoscopic (VAT) approach is an alternative to the standard transvenous technique., Hypothesis: Long-term safety and efficacy of VAT and transvenous LV lead implantation are comparable. To test it, we reviewed our experience and we compared the outcomes of patients who underwent implantation with the two techniques., Methods: The VAT procedure is performed under general anesthesia, with oro-tracheal intubation and right-sided ventilation, and requires two 5 mm and one 15 mm thoracoscopic ports. After pericardiotomy at the spot of the epicardial target area, pacing measurements are taken and a spiral screw electrode is anchored at the final pacing site. The electrode is then tunneled to the pectoral pocket and connected to the device., Results: 105 patients were referred to our center for epicardial LV lead implantation. After pre-operative assessment, 5 patients were excluded because of concomitant conditions precluding surgery. The remaining 100 underwent the procedure. LV lead implantation was successful in all patients (median pacing threshold 0.8 ± 0.5 V, no phrenic nerve stimulation) and cardiac resynchronization therapy was established in all but one patient. The median procedure time was 75 min. During a median follow-up of 24 months, there were no differences in terms of death, cardiovascular hospitalizations or device-related complications vs the group of 100 patients who had undergone transvenous implantation. Patients of both groups displayed similar improvements in terms of ventricular reverse remodeling and functional status., Conclusions: Our VAT approach proved safe and effective, and is a viable alternative in the case of failed transvenous LV implantation., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Aims: A prolonged PR interval is known to be associated with increased mortality and a higher risk of developing atrial fibrillation (AF). We tested the hypothesis that cardiac resynchronization therapy (CRT) is superior to conventional dual-chamber pacing with algorithms for right ventricular pacing avoidance (DDD-VPA) in preserving systolic and diastolic function and in preventing new-onset AF in patients with normal systolic function, indication for pacing and prolonged atrioventricular conduction (PR interval ≥220 ms)., Methods and Results: We randomly assigned 82 patients with ejection fraction >35%, indication for pacing and PR interval ≥220 ms to CRT or to DDD-VPA. On 12-month follow-up examination, the study and control arms did not differ in terms of left ventricular end-systolic volume (44 ± 17 mL vs. 47 ± 16 mL, P = 0.511) or ejection fraction (55 ± 6% vs. 57 ± 8%, P = 0.291). The E to A mitral wave amplitude ratio was higher in the CRT arm (1.3 ± 1.3 vs. 0.8 ± 0.4, P = 0.046) and the E wave deceleration time was longer (262 ± 83 ms vs. 205 ± 51 ms, P = 0.027). Left atrial volume was smaller in the CRT arm (64 ± 17 mL vs. 84 ± 25 mL, P = 0.035). Moreover, the functional class was lower in CRT patients (1.4 ± 0.6 vs. 1.8 ± 0.5, P = 0.010). During follow-up, CRT was associated with a lower risk of new-onset AF [hazard ratio = 0.37 (0.13-0.98), P = 0.046]., Conclusion: Cardiac resynchronization therapy proved superior to DDD-VPA in terms of better diastolic function, less left atrial enlargement and lower risk of new-onset AF, at 12 months. These data need to be confirmed in a larger trial with longer follow-up., Clinical Trial Registration: URL: http://clinicaltrials.gov/ Identifier: NCT02150538., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: In the Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients study, a novel algorithm for heart failure (HF) monitoring was implemented. The HeartLogic (Boston Scientific) index combines data from multiple implantable cardioverter defibrillator (ICD)-based sensors and has proved to be a sensitive and timely predictor of impending HF decompensation. The remote monitoring of HF patients by means of HeartLogic has never been described in clinical practice. We report post-implantation data collected from sensors, the combined index, and their association with clinical events during follow-up in a group of patients who received a HeartLogic-enabled device in clinical practice., Methods and Results: Patients with ICD and cardiac resynchronization therapy ICD were remotely monitored. In December 2017, the HeartLogic feature was activated on the remote monitoring platform, and multiple ICD-based sensor data collected since device implantation were made available: HeartLogic index, heart rate, heart sounds, thoracic impedance, respiration, and activity. Their association with clinical events was retrospectively analysed. Data from 58 patients were analysed. During a mean follow-up of 5 ± 3 months, the HeartLogic index crossed the threshold value (set by default to 16) 24 times (over 24 person-years, 0.99 alerts/patient-year) in 16 patients. HeartLogic alerts preceded five HF hospitalizations and five unplanned in-office visits for HF. Symptoms or signs of HF were also reported at the time of five scheduled visits. The median early warning time and the time spent in alert were longer in the case of hospitalizations than in the case of minor events of clinical deterioration of HF. HeartLogic contributing sensors detected changes in heart sound amplitude (increased third sound and decreased first sound) in all cases of alerts. Patients with HeartLogic alerts during the observation period had higher New York Heart Association class (P = 0.025) and lower ejection fraction (P = 0.016) at the time of activation., Conclusions: Our retrospective analysis indicates that the HeartLogic algorithm might be useful to detect gradual worsening of HF and to stratify risk of HF decompensation., (© 2019 The Authors ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Aims: A recommendation for a subcutaneous-implantable cardioverter-defibrillator (S-ICD) has been added to recent European Society of Cardiology Guidelines. However, the S-ICD is not ideally suitable for patients who need pacing. The aim of this survey was to analyse the current practice of ICD implantation and to evaluate the actual suitability of S-ICD., Methods and Results: The survey 'S-ICD Why Not?' was an independent initiative taken by the Italian Heart Rhythm Society (AIAC). Clinical characteristics, selection criteria, and factors guiding the choice of ICD type were collected in consecutive patients who underwent ICD implantation in 33 Italian centres from September to December 2015. A cardiac resynchronization therapy (CRT) device was implanted in 39% (369 of 947) of patients undergoing de novo ICD implantation. An S-ICD was implanted in 12% of patients with no CRT indication (62 of 510 with available data). S-ICD patients were younger than patients who received transvenous ICD, more often had channelopathies, and more frequently received their device for secondary prevention of sudden death. More frequently, the clinical reason for preferring a transvenous ICD over an S-ICD was the need for pacing (45%) or for antitachycardia pacing (36%). Nonetheless, only 7% of patients fulfilled conditions for recommending permanent pacing, and 4% of patients had a history of monomorphic ventricular tachycardia that might have been treatable with antitachycardia pacing., Conclusion: The vast majority of patients needing ICD therapy are suitable candidates for S-ICD implantation. Nevertheless, it currently seems to be preferentially adopted for secondary prevention of sudden death in young patients with channelopathies., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Many patients fail to receive β-blockers before cardiac resynchronization therapy defibrillator (CRT-D) implantation, or receive them at a suboptimal dose, and require optimization after implantation. We assessed the effectiveness of a structured program for β-blocker titration in CRT-D patients followed up by means of conventional in-clinic visits or remote monitoring., Methods and Results: 130 patients undergoing CRT implantation and treated according to the standard practice of the centers were included as a control group. A second group of 124 CRT-D candidates (Study Group) underwent up-titration visits every 2weeks after implantation (target dose: 10mg/day of bisoprolol or 50mg/day of carvedilol). In the Study Group, remote monitoring was undertaken in 66 patients, who received additional equipment for daily transmission of weight and blood pressure data, and scheduled titration telephone calls. In the Control Group, the maximal dose of β-blockers was being administered to 12 (9%) patients on implantation and 21 (16%) on 6-month follow-up examination (p>0.05). In the Study Group, 25 (20%) patients were receiving the maximal dose of β-blockers on implantation and 72 (58%) on follow-up examination (p<0.001). The 66 Study Group patients on remote monitoring underwent fewer in-clinic visits (p=0.034). Of these, 50 (76%) were on the maximal dose after remote up-titration (versus 38% of patients followed up conventionally, p<0.001). The decrease in left ventricular end-systolic volume was larger in the Study Group (p=0.040)., Conclusions: The program for β-blocker up-titration increased the number of patients reaching the target dose and improved the response to the therapy. The use of remote monitoring and daily transfer of weight and blood pressure data facilitated β-blocker titration., Clinical Trial Registration: URL: http://clinicaltrials.gov/ Identifier: NCT02173028., (Copyright © 2017. Published by Elsevier B.V.)

Aims: It is not known whether heart failure (HF) patients with prolonged QRS who undergo cardiac resynchronization therapy combined with a defibrillator (CRT-D) have a prognostic advantage over HF patients with narrow QRS (therefore without indication for CRT) treated with an implantable cardioverter defibrillator (ICD) only. The aim of this study was to compare the long-term mortality of a group of HF patients with prolonged QRS receiving CRT-D with that of a similar group of patients with narrow QRS receiving ICD only., Methods and Results: A total of 312 patients (mean age 66 ± 13 years; 84% male, mean left ventricular ejection fraction 25 ± 4%, mean New York Heart Association class 2.6 ± 0.5) were included in the analysis. Of these, 138 with a QRS complex duration ≥120 ms received a CRT-D. During follow-up, the time and cause of death were assessed. During a median follow-up of 46 months, CRT-D patients showed significantly lower overall mortality (P = 0.038). Compared with patients receiving ICD only, CRT-D patients showed lower HF mortality (P = 0.003). Coronary mortality, non-cardiac mortality, and sudden mortality were similar in both groups (all P > 0.05). A positive response to CRT was an independent predictor of reduced mortality on multivariate analysis (hazard ratio: 0.27; P = 0.047)., Conclusion: In HF patients treated with ICD, the subgroup of patients with prolonged QRS who receive CRT-D displays better long-term survival than narrow QRS ICD recipients, owing to their reduced HF mortality., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: The longevity of generators is a crucial determinant of the cost-effectiveness of therapy with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-D). We evaluated the trend of device-measured residual battery capacity and longevity projections over 5-year follow-up. We also investigated possible factors associated with battery drain., Methods and Results: Data from 4851 patients in the European LATITUDE(®) database who were followed up for a minimum of 3 years were analysed. The factors associated with battery drain (i.e. year-to-year decrease in residual battery capacity), and thus potentially impacting on device longevity, were mainly the pacing parameters in CRT-D devices and the number of shocks delivered and diverted in both ICD and CRT-D (all P < 0.01 on linear regression analysis). Over the first 5 years, the longevity estimates provided by devices showed low intra-patient variability and increased with time. The estimates exceeded 10 years for CRT-D and 13 and 12 years for single- and dual-chamber ICDs, respectively. In CRT-D patients, the expected patient age on replacement was 80 ± 12 years, and the expected probability of undergoing device replacement was 63 ± 13% for New York Heart Association (NYHA) II patients and 37 ± 16% for NYHA III patients. For comparison, the probabilities of replacing a CRT-D lasting 5 years were 78 ± 8 and 59 ± 13%, respectively (both P < 0.001)., Conclusion: Battery drain was mainly associated with pacing output in CRT-D devices and with the number of capacitor charges in both ICD and CRT-D devices. The longevity estimates provided by the devices were consistent and conservative. According to these estimates, among CRT-D recipients a low proportion of patients should require device replacement., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Previous studies have investigated the role of intrinsic conduction in optimizing cardiac resynchronization therapy. We investigated the role of fusing pacing-induced activation and intrinsic conduction in cardiac resynchronization therapy by evaluating the acute hemodynamic effects of simultaneous His-bundle (HIS) and left ventricular (LV) pacing., Methods and Results: We studied 11 patients with systolic heart failure and left bundle-branch block scheduled for cardiac resynchronization therapy implantation. On implantation, LV pressure-volume data were determined via conductance catheter. Standard leads were placed in the right atrium, at the right ventricular apex, and in a coronary vein. An additional electrode was temporarily positioned in the HIS. The following pacing configurations were systematically assessed: standard biventricular (right ventricular apex+LV), LV-only, HIS, simultaneous HIS and LV (HIS+LV). Each configuration was compared with the AAI mode at multiple atrioventricular delays (AVD). In comparison with the AAI, right ventricular apex+LV and LV-only pacing resulted in improved stroke volume (85±32 mL and 86±33 mL versus 58±23 mL; P<0.001), stroke work, maximum pressure derivative, and systolic dyssynchrony at individually optimized AVD. The optimal AVD was close to the P-H interval in the majority of patients. By contrast, HIS-LV pacing improved hemodynamic indexes at all AVD (stroke volume >76 mL at all fixed intervals and 88±31 mL at optimal interval; all P<0.001)., Conclusions: Standard right ventricular apex+LV and LV-only pacing enhanced systolic function and LV synchrony at individually optimized AVD close to the measured intrinsic P-H interval. By contrast, HIS+LV pacing yielded improvements, regardless of AVD setting. These findings support the hypothesis of the crucial role of intrinsic right ventricular conduction in optimal cardiac resynchronization therapy delivery., (© 2016 American Heart Association, Inc.)

Background: Cardiac resynchronization therapy (CRT) has been demonstrated to improve ventricular-arterial coupling by reducing effective arterial elastance (Ea) on long-term follow-up. Detailed invasive studies showing possible acute peripheral effects of CRT are not available. We evaluated the hemodynamic effects of CRT in patients with systolic dysfunction, in order to investigate the impact on ventricular-arterial coupling and, in particular, on Ea immediately after the initiation of pacing., Methods: We studied 37 heart failure patients undergoing CRT implantation based on conventional criteria. On implantation, left ventricular (LV) pressure and volume data were determined via a conductance catheter. Twelve patients with a standard indication for electrophysiologic study and preserved LV function served as a control group., Results: In comparison with the control group, heart failure patients showed reduced systolic and diastolic function. LV end-systolic elastance (Ees: end-systolic pressure/volume) was impaired (0.79 ± 0.33 mm Hg/mL vs 1.84 ± 0.89 mm Hg/mL, P = 0.012) and Ees/Ea reduced (0.36 ± 0.17 vs 1.19 ± 1.81, P = 0.022). In heart failure patients, CRT immediately improved systolic function, increasing stroke work from 3.9 ± 1.8 L*mm Hg to 6.9 ± 3.3 L*mm Hg (P < 0.001) and Ees to 1.02 ± 0.62 mm Hg/mL (P = 0.001). Ea decreased from 2.59 ± 1.35 mm Hg/mL to 1.68 ± 0.91 mm Hg/mL (P < 0.001), leading to an increase in Ees/Ea to 0.70 ± 0.38 (P < 0.001)., Conclusion: Our data indicate that switching CRT on induces an immediate reduction in arterial load, conceivably as a consequence of restored autonomic balance., (©2015 Wiley Periodicals, Inc.)

Prior studies have suggested that a substantial number of eligible heart failure (HF) patients fail to receive β-blocker therapy, or receive it at a suboptimal dose. The aim of this study is to assess the benefit of a predefined management program designed for β-blocker up-titration, evaluating the synergistic effect of cardiac resynchronization therapy (CRT) and β-blockers in a HF population. The Resynchronization Therapy and β-Blocker Titration (RESTORE) study is a prospective, case-control, multicenter cohort study designed to test the hypothesis that a β-blocker up-titration strategy based on a predefined management program maximizes the beneficial effect of CRT, increasing the number of patients reaching the target dose of β-blockers and improving their clinical outcome. All study patients receive an implantable defibrillator for CRT delivery in accordance with current guidelines. Enrollments started in December 2011 and are scheduled to end in December 2014. Approximately 250 consecutive patients will be prospectively enrolled in 6 Italian centers and followed up for 24 months after implantation. The primary endpoint is to demonstrate that CRT may allow titration of β-blockers until the optimal dose, or at least to the effective dose, in patients with HF. This study might provide important information about the benefit of a predefined management program for β-blocker up-titration in patients receiving CRT. Moreover, assessment of health-care utilization and the consumption of resources will allow estimating the potential utility of remote monitoring by means of an automated telemedicine system in facilitating the titration of β-blockers in comparison with a standard in-hospital approach., (© 2015 Wiley Periodicals, Inc.)

Introduction: The left ventricular (LV) pacing site and the magnitude of the electrical delay within the LV, as expressed by prolonged QRS duration, are major determinants of cardiac resynchronization therapy (CRT) efficacy. We investigated the incremental value of positioning the LV lead in areas of late activation in order to enhance the response to CRT in patients with different degrees of QRS complex lengthening., Methods and Results: This analysis was performed on 301 heart failure patients who received a CRT defibrillator. On implantation, the right ventricular (RV)-to-LV interval was measured as the delay between local activations recorded through the RV and LV leads in the final position. After 1 year, 171 (57%) patients displayed reverse LV remodeling, as measured by a ≥15% reduction in the LV end-systolic volume. Both the RV-to-LV interval and its percentage value corrected for the QRS duration were significantly associated with a positive response to CRT. An RV-to-LV interval >80 milliseconds and an RV-to-LV interval/QRS >58% yielded the best prediction of reverse remodeling. Although the response to CRT decreased with shorter QRS duration in the overall population, patients with an RV-to-LV interval >80 milliseconds showed a response rate >65% in all QRS subgroups., Conclusion: A longer RV-to-LV interval is associated with reverse LV remodeling after CRT. On implantation attempts could be made to maximize it when selecting the LV lead position, especially in patients with shorter QRS duration, and thus less likely to respond positively to CRT., (© 2014 Wiley Periodicals, Inc.)

Background: Previous studies have reported that the left ventricular (LV) pacing site is a major determinant of the hemodynamic response to cardiac resynchronization therapy (CRT). However, lead positioning in a lateral or posterolateral cardiac vein may not be optimal for every patient. The objective of this study was to assess the relationship between the right ventricular (RV)-to-LV conduction time and the systolic function during CRT on the basis of changes to LV pressure-volume loops., Methods: Left ventricular pressure and volume data were determined using a conductance catheter during CRT device implantation in 10 patients. Four endocardial LV sites were systematically assessed at four atrioventricular delays. The RV-to-LV conduction time was measured as the time interval between spontaneous peak R waves, recorded through the RV lead and the LV catheter., Results: The optimal pacing site varied among patients. However, the pacing site associated with the maximum RV-to-LV conduction time resulted in a stroke volume improvement comparable to the pacing site identified through individual hemodynamic optimization (41 ± 17 mL vs 44 ± 18 mL, P = 0.266). Moreover, the RV-to-LV conduction time recorded at each endocardial pacing site correlated positively with the increase in stroke volume (r = 0.537; P < 0.001), stroke work (r = 0.642; P < 0.001), and the pressure-derivative maximum (r = 0.646; P < 0.001) obtained with CRT., Conclusions: An optimal acute response to CRT can be obtained by positioning the LV lead at the site associated with the maximum RV-to-LV conduction time. A significant correlation appears to exist between RV-to-LV conduction time and the improvement in systolic function with CRT., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Background: During cardiac resynchronization therapy (CRT) device implantation, the pacing lead is usually positioned in the coronary sinus (CS) to stimulate the left ventricular (LV) epicardium. Transvenous LV endocardial pacing via transseptal puncture has been proposed as an alternative method. In the present study, we evaluated the acute hemodynamic effects of CRT through LV endocardial pacing in heart failure patients by analyzing LV pressure-volume relationships., Methods and Results: LV pressure and volume data were determined via conductance catheter during CRT device implantation in 10 patients. In addition to the standard epicardial CS pacing, the following endocardial LV sites were systematically assessed: the site transmural to the CS lead, the LV apex, the septal midwall, the basal lateral free wall, and the midlateral free wall. Four atrioventricular delays were tested. There was a significant improvement of systolic function with CRT in all LV pacing configurations, whereas no differences in systolic or diastolic function were detected between LV epicardial and endocardial transmural sites. The optimal pacing site varied among patients but was rarely related to relatively longer activation delays, as assessed by analyzing endocardial electric activation maps. Nonetheless, positioning the pacing lead at the optimal endocardial LV site in each patient significantly improved LV performance in comparison with conventional CS site stimulation (stroke volume, 83 [79-112] mL versus 73 [62-89] mL; P=0.034)., Conclusions: Pacing at the optimal individual LV endocardial site yields enhanced LV performance in comparison with conventional CS site stimulation. Endocardial LV pacing might constitute an alternative approach to CRT, when CS pacing is not viable.

Background: We assessed the influence of clinically significant mitral regurgitation (MR) on clinical-echocardiographic response and outcome in heart failure (HF) patients treated with a biventricular defibrillator (cardiac resynchronization therapy defibrillator [CRT-D])., Methods and Results: A total of 659 HF patients underwent successful implantation of CRT-D and were enrolled in a multicenter prospective registry (median follow-up of 15 months). Following baseline echocardiographic evaluation, patients were stratified into two groups according to the severity of MR: 232 patients with more than mild MR (Group MR+: grade 2, 3, and 4 MR) versus 427 patients with mild (grade 1) or no functional MR (Group MR-). On 6- and 12-month echocardiographic evaluation, MR was seen to have improved in the vast majority of MR+ patients, while it remained unchanged in most MR- patients. On 12-month follow-up evaluation, a comparable response to CRT was observed in the two groups, in terms of the extent of left ventricular reverse remodeling and combined clinical and echocardiographic response. During long-term follow-up, event-free survival did not differ between MR+ and MR- patients, even when subpopulations of patients with ischemic heart disease and with dilated cardiomyopathy were analyzed separately. On multivariate analysis, the only independent predictor of death from any cause was the lack of β-blocker use., Conclusions: This observational analysis supports the use of CRT-D in HF patients with clinically significant MR; MR had no major influence on patient outcome., (©2011, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.)

Background: Algorithms for automatic pacing output adjustment have been implemented in pacemakers and implantable defibrillators (ICD) and recently in cardiac resynchronization therapy defibrillators (CRT-D). We assessed the impact and effectiveness of these automatic features., Method and Results: We prospectively enrolled patients successfully implanted with the following Medtronic CRT-Ds: Concerto [with automatic left ventricular (LV) output management algorithm], Consulta [automatic management of atrial, right ventricular (RV) and LV voltage], and Sentry (only manual voltage adjustments). Patients with complete device data available for at least 12 months were included in the analysis. We analysed data from 739 patients (360 Sentry, 335 Concerto, 44 Consulta). During the first 6 months, the LV pacing amplitude underwent more frequent adjustments in Concerto (63%, P< 0.001) and Consulta (64%, P= 0.047) patients than in Sentry (48%). Similarly, RV and atrial amplitude at 6 months differed from the pre-discharge value more frequently in Consulta (61 and 50%, respectively) than in Sentry patients (33 and 28%, both P< 0.01). The LV pulse amplitude for Concerto and the voltages in the three chambers of Consulta were significantly lower than the corresponding values programmed in Sentry at 6 and 12 months. The proportion of CRT-D interrogations involving manual reprogramming was 97 ± 8% for Sentry, 79 ± 20% for Concerto, and 56 ± 16% for Consulta (all P< 0.001)., Conclusions: Algorithms for the automatic management of the pacing output reduced pacing output in comparison with the standard manual management approach, with potential optimization of battery longevity. Moreover, they reduced the need to manually reprogram CRT-Ds, suggesting the possibility to simplify CRT-D management and facilitate remote monitoring.

Background: Long-term data on device-related untoward events in patients receiving defibrillators for resynchronization therapy (CRT-D) are lacking. We quantified the frequency of repeat invasive procedures and the nature of long-term complications in current clinical practice and examined possible predictors of device-related events and their association with long-term patient outcome., Methods and Results: We analyzed data from 3253 patients who underwent de novo successful implantation of CRT-D and were followed up for a median of 18 months (25th to 75th percentiles: 9 to 30) in 117 Italian centers. Device-related events were reported in 416 patients, and, specifically, surgical interventions for system revision were described in 390 patients. Four years after the implantation procedure, 50% of patients underwent surgical revision for battery depletion and 14% for unanticipated events. For comparison, at 4 years battery depletion occurred in 10% and 13% of patients who received single- and dual-chamber defibrillators at the study centers, and unanticipated events were reported as 4% and 9%, respectively. In CRT-D, infections occurred at a rate of 1.0%/y, and the risk of infections increased after device replacement procedures (hazard ratio, 2.04; 95% confidence interval, 1.01 to 4.09; P=0.045). Left ventricular lead dislodgements were reported at a rate of 2.3%/y and were predicted by longer fluoroscopy time and higher pacing threshold on implantation. Device-related events were not associated with a worse clinical outcome; indeed, the risk of death was similar in patients with and without surgical revision (hazard ratio, 0.90; 95% confidence interval, 0.56 to 1.47; P=0.682)., Conclusions: In current clinical practice device-related events are more frequent in CRT-D than in single- or dual-chamber defibrillators, and are frequently managed by surgical intervention for system revision. However, a worse clinical outcome is not associated with these events., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01007474.

Chronic heart failure is one of the most important geriatric syndromes, associated with disability, increased hospital admissions, and high mortality. The aim of this study was to evaluate the existence of age-related differences in clinical effectiveness and outcomes of cardiac resynchronization therapy (CRT), alone or in combination with an implantable cardioverter-defibrillator (CRT-D), in a large, real-world registry. A total of 1,787 patients admitted for CRT or CRT-D to the 117 centers participating in the InSync/InSync ICD Italian Registry from 1999 to 2005 were evaluated. Patients were divided into 3 age groups: <65 years (n = 571), 65 to 74 years (n = 740), and ≥75 years (n = 476). The left ventricular ejection fraction did not differ in the 3 groups (26 ± 8% vs 26 ± 7% vs 27 ± 8%, p = 0.123). Atrial fibrillation prevalence demonstrated an age-related increase. The use of recommended medical therapy for chronic heart failure decreased with age, as well as CRT-D implantation (p <0.001). The percentage of echocardiographic responders to CRT was similar in the 3 groups, and New York Heart Association class significantly improved independent of age. During the follow-up period (19 ± 13 months), all-cause mortality was higher in patients aged ≥75 years than in those aged <65 years (p = 0.005). In the whole population, mortality was associated with the nonresponder condition, the presence of atrial fibrillation and the lack of prescription of recommended medical therapy. In conclusion, CRT improved left ventricular performance and functional capacity independent of age. The proportion of the responder condition to CRT was the same in all groups. Pharmacologic undertreatment is an important issue in a "real-world" geriatric population., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Aims: The left ventricular (LV) lead for cardiac resynchronization therapy (CRT) is usually positioned in the coronary sinus via a stylet-guided or an 'over-the-wire' approach. Recently, a new tool has been developed, the Medtronic Attain Hybrid, that combines guide-wire and stylet features. We assessed its safety and efficacy in comparison with standard tools currently used in clinical practice., Methods and Results: Patients undergoing standard CRT device implantation were enrolled in seven Italian centres. In the preliminary phase of the study (Phase I), data were collected during implantation procedures performed with standard tools (three patients per centre). Subsequently, the Attain Hybrid was made available in the centres and data were collected for all consecutive patients undergoing implantation during the following year. A learning phase was considered (Phase II), and the last three patients per centre (Phase III) were used for comparison with Phase I. One hundred and seventeen patients were enrolled: 21 patients in Phase I, 75 in Phase II, and 21 in Phase III. Rates of successful implantation were similar in Phases I and III (95 vs. 100%, P=1.000). The pre-defined target vein was reached in 15 (71%) patients in Phase I and in 21 (100%) patients in Phase III (P=0.021). In 10 (48%) procedures during Phase I, LV lead positioning necessitated switching from guide-wire to stylet; this proportion decreased during Phase III (14%, P=0.043). Mean LV positioning time was 16±7 min in Phase I and 11±6 min in Phase III (P=0.040). No adverse events or lead-related complications were detected on implantation or during a follow-up of 6±4 months., Conclusion: The Attain Hybrid is safe and effective. It significantly improves target vein accessibility and reduces procedural time in comparison with conventional tools.

Background: "Cardiac memory" (CM) refers to a change in repolarization induced by an altered pathway of activation. The effects of biventricular pacing on CM induction have not been investigated., Objective: To investigate the development of CM during cardiac resynchronization therapy (CRT) through vectorcardiography (VCG)., Methods: Eleven patients undergoing CRT were enrolled. VCG was acquired during spontaneous ventricular activation at baseline and during AAI and DDD pacing immediately after and 7, 14, 21 and 60 days after the implantation., Results: At 1-week follow-up, during AAI pacing T vector angles significantly changed (azimuth 23 ± 19°; p = 0.002; elevation 23 ± 27°; p = 0.019) and magnitude significantly increased (baseline 1.13 ± 0.69 mV; 7 days: 1.77 ± 1.27 mV; p = 0.026). T angle changes remained stable throughout the follow-up period while a further significant increase in magnitude was observed at 60 days (2.21 ± 1.50 mV; p = 0.01 vs. baseline and p = 0.04 vs. 7 days). Paced T vector magnitude at implant (2.24 ± 1.25 mV) decreased significantly at 7 days (1.64 ± 1.26 mV; p = 0.030) with a further significant decrease at 60 days (1.40 ± 1.18 mV; p = 0.003 vs. baseline; p = 0.02 vs. 7 days)., Conclusion: CRT induces a significant change in T vector magnitude, azimuth, and elevation after resumption of spontaneous ventricular activation after 7 days from implantation. While further changes in T vector angle were not observed, after 2 months of CRT a significant decrease of paced T vector magnitude and a significant increase of spontaneous T vector magnitude were observed.