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Importance: Approximately 40% of patients with heart failure (HF) who are eligible for cardiac resynchronization therapy (CRT) either fail to respond or are untreatable due to anatomical constraints., Objective: To assess the safety and efficacy of a novel, leadless, left ventricular (LV) endocardial pacing system for patients at high risk for a CRT upgrade or whose coronary sinus (CS) lead placement/pacing with a conventional CRT system failed., Design, Setting, and Participants: The SOLVE-CRT study was a prospective multicenter trial enrolling January 2018 through July 2022, with follow-up at 6 months. Data were analyzed from January 17, 2018, through February 15, 2023. The trial combined data from an initial randomized, double-blind study (n = 108) and a subsequent single-arm part (n = 75). It took place at 36 centers across Australia, Europe, and the US. Participants were nonresponders, previously untreatable (PU), or high-risk upgrades (HRU). All participants contributed to the safety analysis. The primary efficacy analysis (n = 100) included 75 PU-HRU patients from the single-arm part and 25 PU-HRU patients from the randomized treatment arm., Interventions: Patients were implanted with the WiSE CRT System (EBR Systems) consisting of a leadless LV endocardial pacing electrode stimulated with ultrasound energy delivered by a subcutaneously implanted transmitter and battery., Main Outcomes and Measures: The primary safety end point was freedom from type I complications. The primary efficacy end point was a reduction in mean LV end systolic volume (LVESV)., Results: The study included 183 participants; mean age was 68.1 (SD, 10.3) years and 141 were male (77%). The trial was terminated at an interim analysis for meeting prespecified stopping criteria. In the safety population, patients were either New York Heart Association Class II (34.6%) or III (65.4%). The primary efficacy end point was met with a 16.4% (95% CI, -21.0% to -11.7%) reduction in mean LVESV (P = .003). The primary safety end point was met with an 80.9% rate of freedom from type I complications (P < .001), which included 12 study device system events (6.6%), 5 vascular events (2.7%), 3 strokes (1.6%), and 7 cardiac perforations which mostly occurred early in the study (3.8%)., Conclusions and Relevance: The SOLVE-CRT study has demonstrated that leadless LV endocardial pacing with the WiSE CRT system is associated with a reduction in LVESV in patients with HF. This novel system may represent an alternative to conventional CRT implants in some HF patient populations., Trial Registration: ClinicalTrials.gov Identifier: NCT0292203.

Background: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well-established therapy in patients with reduced left ventricular ejection fraction, heart failure, and left bundle branch block. Left bundle branch area pacing (LBBAP) has recently been shown to be a feasible and effective alternative to BVP. Comparative data on the risk of complications between LBBAP and BVP among patients undergoing CRT are lacking., Objective: The aim of this study was to compare the long-term risk of procedure-related complications between LBBAP and BVP in a cohort of patients undergoing CRT., Methods: This prospective, multicenter, observational study enrolled 668 consecutive patients (mean age 71.2 ± 10.0 years; 52.2% male; 59.4% with New York Heart Association class III-IV heart failure symptoms) with left ventricular ejection fraction 33.4% ± 4.3% who underwent BVP (n = 561) or LBBAP (n = 107) for a class I or II indication for CRT. Propensity score matching for baseline characteristics yielded 93 matched pairs. The rate and nature of intraprocedural and long-term post-procedural complications occurring during follow-up were prospectively collected and compared between the 2 groups., Results: During a mean follow-up of 18 months, procedure-related complications were observed in 16 patients: 12 in BVP (12.9%) and 4 in LBBAP (4.3%) (P = .036). Compared with patients who underwent LBBAP, those who underwent BVP showed a lower complication-free survival (P = .032). In multivariate analysis, BVP resulted an independent predictive factor associated with a higher risk of complications (hazard ratio 3.234; P = .042). Complications related to the coronary sinus lead were most frequently observed in patients who underwent BVP (50.0% of all complications)., Conclusion: LBBAP was associated with a lower long-term risk of device-related complications compared with BVP in patients with an indication for CRT., Competing Interests: Disclosures The authors have no conflicts to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular assist devices (LVADs) are an increasingly used strategy for the management of patients with advanced heart failure (HF). Subcutaneous implantable cardioverter defibrillator (S-ICD) might be a viable alternative to conventional ICDs with a lower risk of short- and long-term of device-related complications and infections.The aim of this multicenter study was to evaluate the outcomes and management of S-ICD recipients who underwent LVAD implantation., Methods: The study population included patients with a preexisting S-ICD who underwent LVAD implantation for advanced HF despite optimal medical therapy., Results: The study population included 30 patients (25 male; median age 45 [38-52] years).The HeartMate III was the most common LVAD type. Median follow-up in the setting of concomitant use of S-ICDs and LVADs was 7 months (1-20).There were no reports of inability to interrogate S-ICD systems in this population. Electromagnetic interference (EMI) occurred in 21 (70%) patients. The primary sensing vector was the one most significantly involved in determining EMI. Twenty-seven patients (90%) remained eligible for S-ICD implantation with at least one optimal sensing vector. The remaining 3 patients (10%) were ineligible for S-ICD after attempts of reprogramming of sensing vectors. Six patients (20%) experienced inappropriate shocks (IS) due to EMI. Six patients (20%) experienced appropriate shocks. No S-ICD extraction because of need for antitachycardia pacing, ineffective therapy or infection was reported., Conclusions: Concomitant use of LVAD and S-ICD is feasible in most patients. However, the potential risk of EMI oversensing, IS and undersensing in the post-operative period following LVAD implantation should be considered. Careful screening for EMI should be performed in all sensing vectors after LVAD implantation., Competing Interests: Declaration of competing interest This was an independent study. No external funding was received for this project. CT is a member of Boston Scientific advisory board; FM scientific consultant for Boston Scientific and Cook Medical. RT is a consultant for BostonScientific and received speaker's honoraria from Boston Scientific. Other authors do no report disclosures regarding this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Conduction system pacing (CSP), including His-bundle pacing (HBP) and left bundle branch area pacing (LBBAP), have been proposed as alternatives to biventricular pacing (BVP) in patients scheduled for ablate and pace (A&P) strategy. The aim of this study was to compare the clinical outcomes, including the rate and nature of device-related complications, between BVP and CSP in a cohort of patients undergoing A&P., Methods: Prospective, multicenter, observational study, enrolling consecutive patients undergoing A&P. The risk of device-related complications and of heart failure (HF) hospitalization was prospectively assessed., Results: A total of 373 patients (75.3 ± 8.7 years, 53.9% male, 68.9% with NYHA class ≥III) were enrolled: 263 with BVP, 68 with HBP, and 42 with LBBAP. Baseline characteristics of the three groups were similar. Compared to BVP and HBP, LBBAP was associated with the shortest mean procedural and fluoroscopy times and with the lowest acute capture thresholds (all p < .05). At 12-month follow-up LBBAP maintained the lowest capture thresholds and showed the longest estimated residual battery longevity (all p < .05). At 12-months follow-up the three study groups showed a similar risk of device-related complications (5.7%, 4.4%, and 2.4% for BVP, HBP, and LBBAP, respectively; p = .650), and of HF hospitalization (2.7%, 1.5%, and 2.4% for BVP, HBP, and LBBAP, respectively; p = .850)., Conclusions: In the setting of A&P, CSP is a feasible pacing modality, with a midterm safety profile comparable to BVP. LBBAP offers the advantage of reducing procedural times and obtaining lower and stable capture thresholds, with a positive impact on the device longevity., (© 2023 Wiley Periodicals LLC.)

This review illustrates the pathophysiological aspects and available scientific evidence on molecular mechanisms about cardiac contractility modulation (CCM) therapy. The main advances in understanding the effect of this electrical therapy at cellular level in the heart are critically discussed in light of the data from clinical trials supporting the use of CCM therapy in patients with heart failure across a wide range of left ventricular ejection fraction values. This electrical therapy triggers a physiological cellular response leading to an improvement of cardiac performance and reverse ventricular remodeling, with no increase in oxygen consumption. The present review deals with the new potential applications of CCM for patients with chronic heart failure and paves the way for the development of a longitudinal Italian registry of patients implanted with this cardiac device.

Background: The noninferiority of left ventricular pacing alone (LVp) compared with biventricular pacing (BIV) has not been yet definitely documented. In this study, we reviewed all the original echocardiographic measures of the Biventricular versus Left Univentricular Pacing with ICD Back-up in Heart Failure Patients (B-LEFT HF) trial in order to investigate mechanisms underlying LV remodelling with both pacing modalities., Methods: Patients with New York Heart Association functional class (NYHA) III or IV despite optimal medical therapy, LVEF 35% or less, left ventricular end-diastolic diameter (LVEDD) more than 55 mm, QRS duration at least 130 ms were randomized to BIV or LVp for 6 months. The primary end point was a composite of at least 1 point decrease in NYHA class and at least 5 mm decrease in left ventricular end-systolic diameter (LVESD). An additional end point was a LVp reverse remodelling defined as at least 10% decrease in LVESD. Mitral regurgitation and all echocardiographic measures were reassessed after 6-month follow-up., Results: One hundred and forty-three patients were enrolled. Seventy-six patients were in the BIV and 67 were in the LVp group. Left ventricular volumes decreased significantly without difference between groups (P = 0.8447). Similarly, left ventricular diameters decreased significantly in both groups with a significant decrease in LVESD with BIV (P < 0.0001), but not with LVp (P = 0.1383). LVEF improved in both groups without difference (P = 0.8072). Mitral regurgitation did not improve either with BIV, or with LVp., Conclusion: The echocardiographic sub-analysis of B-LEFT study showed the substantial equivalence of LVp in favouring left ventricular reverse remodelling as compared with BIV., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Patients with ischemic cardiomyopathy, non-left bundle branch block, or QRS duration <150 ms have a lower response rate to cardiac resynchronization therapy (CRT) than did other indicated patients. The ECG Belt system (EBS) is a novel surface mapping system designed to measure electrical dyssynchrony via the standard deviation of the activation times of the left ventricle., Objectives: The objectives of this study were to evaluate the efficacy of the EBS in patients less likely to respond to CRT and to determine whether EBS use in lead placement guidance and device programming was superior to standard CRT care., Methods: This was a prospective randomized trial of patients with heart failure and EBS-guided CRT implantation and programming vs standard CRT care. The primary end point was relative change in left ventricular end-systolic volume from baseline to 6 months postimplantation., Results: A total of 408 patients from centers in Europe and North America were randomized. Although both patients with EBS and control patients had a mean improvement in left ventricular end-systolic volume, there was no significant difference in relative change from baseline (P = .26). While patients with a higher baseline standard deviation of the activation times derived greater left ventricular reverse remodeling, improvement in electrical dyssynchrony did not correlate with the extent of reverse remodeling., Conclusion: The findings of the present study do not support EBS-guided therapy for CRT management of heart failure with reduced ejection fraction., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Elevated resting heart rate is a risk factor for cardiovascular events., Objective: The purpose of this study was to investigate the clinical significance of nocturnal heart rate (nHR) and 24-hour mean heart rate (24h-HR) obtained by continuous remote monitoring (RM) of implantable devices., Methods: We analyzed daily-sampled trends of nHR, 24h-HR, and physical activity in patients on β-blocker therapy for chronic heart failure and with implantable cardioverter-defibrillators or cardiac resynchronization therapy defibrillators (CRT-Ds). Patients were grouped by average nHR and 24h-HR quartile during follow-up to estimate the respective incidence of nonarrhythmic death and device-treated ventricular tachycardia/fibrillation (VT/VF)., Results: The study cohort included 1330 patients (median age 69 years [interquartile range 61-77 years]; 41% [n = 550] with CRT-D; median follow-up 25 months [interquartile range 13-42 months]). Compared with patients in the lowest nHR quartile (≤57 beats/min) group, patients in the highest quartile group (>65 beats/min) had an increased risk of nonarrhythmic death (adjusted hazard ratio [AHR] 2.25; 95% confidence interval [CI] 1.13-4.50; P = .021) and VT/VF (AHR 1.98; 95% CI 1.40-2.79; P < .001) and were characterized by the lowest level of physical activity (P ≤ .0004 vs every other nHR quartiles). The highest 24h-HR quartile group (>75 beats/min) showed an increased risk of VT/VF (AHR 2.13; 95% CI 1.52-2.99; P < .001) and a weaker though significant association with nonarrhythmic mortality (AHR 1.80; 95% CI 1.00-3.22; P = .05) as compared with the lowest 24h-HR quartile group (≤65 beats/min)., Conclusion: In remotely monitored patients with implantable cardioverter-defibrillator/CRT-D on β-blocker therapy for heart failure, elevated heart rates (nHR >65 beats/min and 24h-HR >75 beats/min) were associated with increased mortality and VT/VF risk. nHR showed a stronger association than 24h-HR with worst prognosis and lowest physical activity., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: In patients with symptomatic permanent atrial fibrillation (PEAF) and narrow QRS, atrio-ventricular junction ablation (AVJA) plus cardiac resynchronization therapy (CRT) is superior to medical therapy in reducing heart failure (HF) hospitalization and all-cause mortality. To compare the mortality of a population of patients with HF, reduced EF (rEF), and PEAF treated with AVJA plus CRT with that of a contemporary cohort of patients in sinus rhythm (SR) with similar baseline characteristics., Methods and Results: In this prospective, multicentre, observational study, all-cause mortality in a group of consecutive patients undergoing AVJA and implantable cardioverter-defibrillator (ICD) combined with CRT implantation for HFrEF, narrow QRS, and PEAF with uncontrolled ventricular rate was compared with that of a contemporary cohort of patients in SR undergoing ICD implantation (not combined with CRT) for HFrEF and narrow QRS. Individual 1:1 propensity matching of baseline characteristics was performed. A total of 824 patients were enrolled. Propensity matching yielded 107 matched pairs. After a median follow-up of 52 months, all-cause mortality was similar in patients treated with AVJA plus CRT and in the control group (p = .434). In AVJA plus CRT patients, mortality was significantly lower than in control group patients with a history of paroxysmal/persistent AF (n = 45, p = .020), and similar to that of patients without a history of AF (n = 62, p = .459)., Conclusions: After adjustment for patient characteristics, the long-term prognosis of patients with HFrEF, narrow QRS, and PEAF who underwent AVJA plus CRT was similar to that of a population of patients in SR with similar characteristics., (© 2022 Wiley Periodicals LLC.)

Purpose: The purpose of this study was to assess the available mortality risk stratification models for implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) patients., Methods: We conducted a review of mortality risk stratification models and tested their ability to improve prediction of 1-year survival after implant in a database of patients who received a remotely controlled ICD/CRT-D device during routine care and included in the independent Home Monitoring Expert Alliance registry., Results: We identified ten predicting models published in peer-reviewed journals between 2000 and 2021 (Parkash, PACE, MADIT, aCCI, CHA2DS2-VASc quartiles, CIDS, FADES, Sjoblom, AAACC, and MADIT-ICD non-arrhythmic mortality score) that could be tested in our database as based on common demographic, clinical, echocardiographic, electrocardiographic, and laboratory variables. Our cohort included 1,911 patients with left ventricular dysfunction (median age 71, 18.3% female) from sites not using any risk stratification score for systematic patient screening. Patients received an ICD (53.8%) or CRT-D (46.2%) between 2011 and 2017, after standard physician evaluation. There were 56 deaths within 1-year post-implant, with an all-cause mortality rate of 2.9% (95% confidence interval [CI], 2.3-3.8%). Four predicting models (Parkash, MADIT, AAACC, and MADIT-ICD non-arrhythmic mortality score) were significantly associated with increased risk of 1-year mortality with hazard ratios ranging from 3.75 (CI, 1.31-10.7) to 6.53 (CI 1.52-28.0, p ≤ 0.014 for all four). Positive predictive values of 1-year mortality were below 25% for all models., Conclusion: In our analysis, the models we tested conferred modest incremental predicting power to ordinary screening methods., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Relatively few data are available on long-term survival and incidence of ventricular arrhythmias in cardiac resynchronization therapy (CRT) patients. We investigated long-term outcomes of CRT patients with non-ischemic dilated cardiomyopathy stratified as responders or non-responders according to radionuclide angiography., Methods: Fifty patients with non-ischemic dilated cardiomyopathy undergoing CRT were assessed by equilibrium Tc 99 radionuclide angiography with bicycle exercise at baseline and after 3 months. Intra- and interventricular dyssynchrony were derived by Fourier phase analysis. Patient clinical outcome was assessed after 10 years., Results: At 3 months, 50% of patients were identified as CRT responders according to an increase in LV ejection fraction ≥ 5%. During a follow-up of 109 ± 48 months, 30% of patients died and 6% underwent heart transplantation. Age and history of paroxysmal atrial fibrillation were found to be predictors of all-cause mortality. CRT responders showed lower risk of death from cardiac causes than non-responders. At follow-up, 38% of patients presented at least one episode of sustained ventricular tachycardia, with a similar percentage between responders and non-responders., Conclusion: At long-term follow-up, non-ischemic CRT recipients identified as responders by radionuclide angiography were found to be at lower risk of worsening heart failure death than non-responders. Long-term risk for sustained ventricular arrhythmia was similar between CRT responders and non-responders., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Left ventricular (LV) lead optimal positioning is one of the most important determinants of cardiac resynchronization therapy (CRT) success. LV quadripolar active fixation (QAF) leads have been designed to ensure stable LV pacing in the target area and reduce the likelihood of phrenic nerve stimulation (PNS). The aim of this analysis is to compare performances, safety, and clinical outcomes of QAF with those of quadripolar passive fixation leads (QPL) and bipolar active fixation (BAF) leads in a real-world cohort of CRT patients., Methods and Results: This retrospective analysis compared the procedure and follow-up data of 117 QAF included in the One Hospital ClinicalService project from nine Italian hospitals with two historical cohorts of 261 BAF and 124 QPL. QAF enabled basal pacing more frequently than QPL (24.1% vs. 6.5%, p < .001) but not differently from BAF (p = .981). At implant, mean QAF LV myocardial threshold (LVMT) was 1.21 ± 0.8 V at 0.4 ms, not different from that of BAF (p = .346) and QPL (p = .333). At a median follow-up of 22 months, LVMT was 1.37 ± 0.90 V (p = .036 vs. implant). Acute LV lead dislodgment occurrence was low in all cohorts: 1 (0.9%) in QAF, 4 in BAF (1.5%), and none (0.0%) in QPL. During follow-up, total LV-related complication rate was lower in QAF (0.5/100 patient-years) than in BAF (4.2/100 patient-years, p = .014) and QPL (3.6/100 patient-years, p = .055). QAF, BAF, and QPL annual rate of heart failure hospitalization were respectively 6.1/100 patient-years, 2.5/100 patient-years (p = .081), and 3.6/100 patient-years (p = .346). CRT responders' rate in QAF was 69.9%, with no difference in comparison to BAF (p = .998) and QPL (p = .509). During follow-up, mean left ventricular ejection fraction (LVEF) of QAF increased from 31.8 ± 10.1% to 40.3 ± 10.7% (p < .001). The average degree of echocardiographic response (ΔLVEF) did not differ between QAF and other cohorts; however, LVEF CRT responder's distribution of QAF differs from those of BAF (p = .003) and QPL (p = .022), due to a higher percentage of super-responders., Conclusions: QAF with short interelectrode spacing resulted in non-inferior clinical outcomes and CRT responders' rate in comparison to BAF and QPL, while reducing complication rate during follow-up and increasing the possibilities of electronic repositioning to manage PNS or to optimize resynchronization therapy., (© 2022 Wiley Periodicals LLC.)

Nuclear imaging techniques like single-photon emission computed tomography (SPECT) and radionuclide angiography have wide applications in patients receiving a cardiac implantable electrical device (CIED), who cannot usually undergo cardiac magnetic resonance. Our aim was to provide an update of single-photon imaging clinical applications, with a specific focus on CIED recipients. SPECT imaging is commonly used in CIED patients to assess myocardial perfusion, but it can also be used to evaluate myocardial viability, which is an important predictor of LV function improvement by cardiac resynchronization therapy (CRT). Radionuclide angiography has shown higher temporal resolution and reproducibility than SPECT in the evaluation of cardiac function and dyssynchrony. Left ventricular dyssynchrony as assessed by radionuclide angiography with phase analysis may be reliably used for CRT patient selection and evaluation of CRT response. SPECT imaging with meta-iodo-benzyl-guanidine allows for cardiac sympathetic innervation examination, which may be used for prognostic stratification of heart failure patients and prediction of ventricular tachyarrhythmias. Finally, promising results in CIED infection diagnosis have been shown by SPECT with radiolabeled autologous white blood cells., (© 2020. American Society of Nuclear Cardiology.)

Objectives: To describe a cohort of patients with arrhythmogenic left ventricular cardiomyopathy (ALVC), focusing on the spectrum of the clinical presentations., Methods: Patients were retrospectively evaluated between January 2012 and June 2020. Diagnosis was based on (1) ≥3 contiguous segments with subepicardial/midwall late gadolinium enhancement in the left ventricle (LV) at cardiac magnetic resonance plus a likely pathogenic/pathogenic arrhythmogenic cardiomyopathy (AC) associated genetic mutation and/or familial history of AC and/or red flags for ALVC (ie, negative T waves in V4-6/aVL, low voltages in limb leads, right bundle branch block like ventricular tachycardia) or (2) pathology examination of explanted hearts or autoptic cases suffering sudden cardiac death (SCD). Significant right ventricular involvement was an exclusion criterion., Results: Fifty-two patients (63% males, age 45 years (31-53)) composed the study cohort. Twenty-one (41%) had normal echocardiogram, 13 (25%) a hypokinetic non-dilated cardiomyopathy (HNDC) and 17 (33%) a dilated cardiomyopathy (DCM). Of 47 tested patients, 29 (62%) were carriers of a pathogenic/likely pathogenic DNA variant. Clinical contexts leading to diagnosis were SCD in 3 (6%), ventricular arrhythmias in 15 (29%), chest pain in 8 (15%), heart failure in 6 (12%) and familial screening in 20 (38%). Thirty patients (57%) had previously received a diagnosis other than ALVC with a diagnostic delay of 6 years (IQR 1-7)., Conclusions: ALVC is hidden in different clinical scenarios with a phenotypic spectrum ranging from normal LV to HNDC and DCM. Ventricular arrhythmias, chest pain, heart failure and SCD are the main clinical presentations, being familial screening essential for the affected relatives' identification., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cardiac simulation has moved from early life-saving pacemakers meant only to prevent asystole to current devices capable of physiologic stimulation for the treatment of heart rhythm and heart failure, that are also intended for remote patient and disease-progression monitoring. The actual vision of contemporary pacing aims to correct the electrophysiologic roots of mechanical inefficiency regardless of underlying structural heart diseases. The awareness of the residual cardiac dyssynchrony related to customary cardiac pacing has changed the concept of what truly represents "physiologic pacing". On a different perspective, leadless stimulation to abolish CIED surgery and prevent lead-related complications is becoming a priority both for young device recipients and for frail, elderly patients. Careful clinical evaluation attempts to bridge decision-making to patient-tailored therapy., Competing Interests: Mauro Biffi: educational activity and Speaker’s bureau for Biotronik, Boston Scientific, Medtronic, and Zoll. The other authors declare no conflicts of interest., (© 2022 The Author(s). Published by IMR Press.)

Aims: Cardiac resynchronization therapy (CRT) is indicated in patients with systolic heart failure (HF), severe left ventricle (LV) dysfunction and interventricular dyssynchrony.In prospective observational research, we aimed to evaluate whether CRT-induced LV reverse remodelling and occurrence of ventricular arrhythmias (VT/VF) independently contribute to prognosis in patients with CRT defibrillators (CRT-D)., Methods: In 95 Italian cardiological centres, after a screening period of 6 months, patients were categorized according to VT/VF occurrence and CRT response, defined as LV end-systolic volume relative reduction >15% or LV ejection fraction absolute increase >5%. The main endpoint was death or HF hospitalizations., Results: Among 1308 CRT-D patients (80% male, mean age 66 years), at 6 months, follow-up 71% were identified as CRT responders and 12% experienced appropriate VT/VF detections. The main endpoint was significantly and independently associated with previous myocardial infarction, New York Heart Association Class, VT/VF occurrence and with CRT response. CRT nonresponder patients who suffered VT/VF in the screening period had a risk of death or HF hospitalizations [HR = 7.82, 95% confidence interval (CI) = 3.95-15.48] significantly (P < 0.001) higher than CRT responders without VT/VF occurrence. This risk is mitigated without VT/VF occurrence (HR = 3.47, 95% CI = 2.03-5.91, P < 0.001) or in case of CRT response (HR = 3.11, 95% CI = 1.44-6.72, P = 0.004)., Conclusion: Our data show that both CRT response and occurrence of VT/VF independently contribute to the risk of death or HF-related hospitalizations in CRT-D patients. Early VT/VF occurrence may be identified as a marker of disease severity than can be mitigated by CRT response both in terms of all-cause mortality and long-term VT/VF onset., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00147290 and NCT00617175., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: Cardiac resynchronization therapy (CRT) upgrades may be less likely to improve following intervention. Leadless left ventricular (LV) endocardial pacing has been used for patients with previously failed CRT or high-risk upgrades. We compared procedural and long-term outcomes in patients undergoing coronary sinus (CS) CRT upgrades with high-risk and previously failed CRT upgrades undergoing LV endocardial upgrades., Method and Results: Prospective consecutive CS upgrades between 2015 and 2019 were compared with those undergoing WiSE-CRT implantation. Cardiac resynchronization therapy response at 6 months was defined as improvement in clinical composite score (CCS) and a reduction in LV end-systolic volume (LVESV) ≥15%. A total of 225 patients were analysed; 121 CS and 104 endocardial upgrades. Patients receiving WiSE-CRT tended to have more comorbidities and were more likely to have previous cardiac surgery (30.9% vs. 16.5%; P = 0.012), hypertension (59.2% vs. 34.7%; P < 0.001), chronic obstructive airways disease (19.4% vs. 9.9%; P = 0.046), and chronic kidney disease (46.4% vs. 21.5%; P < 0.01) but similar LV ejection fraction (30.0 ± 8.3% vs. 29.5 ± 8.6%; P = 0.678). WiSE-CRT upgrades were successful in 97.1% with procedure-related mortality in 1.9%. Coronary sinus upgrades were successful in 97.5% of cases with a 2.5% rate of CS dissection and 5.6% lead malfunction/displacement. At 6 months, 91 WiSE-CRT upgrades and 107 CS upgrades had similar improvements in CCS (76.3% vs. 68.5%; P = 0.210) and reduction in LVESV ≥15% (54.2% vs. 56.3%; P = 0.835)., Conclusion: Despite prior failed upgrades and high-risk patients with more comorbidities, WiSE-CRT upgrades had high rates of procedural success and similar improvements in CCS and LV remodelling with CS upgrades., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This critical review illustrates the pathophysiological aspects and available scientific evidence about cardiac contractility modulation therapy. A useful algorithm dealing with the essential decisional knots to consider for device implantation in patients with heart failure in NYHA class >II and ejection fraction ≤45% is presented. The present review paves the way for the development of an Italian registry aiming at analyzing the characteristics of implanted patients based on a multiparametric approach, including cardiac biomarkers, to identify clinical profiles and predictors of response to therapy. The "Answers and Questions" section provides useful insights into pathophysiology, technical specifications, clinically relevant scenarios and future perspectives.

Background: Device replacement is the ideal time to reassess health care goals regarding continuing implantable cardioverter-defibrillator (ICD) therapy. Only few data are available on the decision making at this time., Objectives: The goals of this study were to identify factors associated with poor prognosis at the time of ICD replacement and to develop a prognostic index able to stratify those patients at risk of dying early., Methods: DEtect long-term COmplications after implantable cardioverter-DEfibrillator replacement (DECODE) was a prospective, single-arm, multicenter cohort study aimed at estimating long-term complications in a large population of patients who underwent ICD/cardiac resynchronization therapy - defibrillator replacement. Potential predictors of death were investigated, and all these factors were gathered into a survival score index (SUSCI)., Results: We included 983 consecutive patients (median age 71 years (63-78)); 750 (76%) were men, 537 (55%) had ischemic cardiomyopathy; 460 (47%) were implanted with cardiac resynchronization therapy - defibrillator. During a median follow-up period of 761 days (interquartile range 628-904 days), 114 patients (12%) died. In multivariate Cox regression analysis, New York Heart Association class III/IV, ischemic cardiomyopathy, body mass index < 26 kg/m 2 , insulin administration, age ≥ 75 years, history of atrial fibrillation, and hospitalization within 30 days before ICD replacement remained associated with death. The survival score index showed a good discriminatory power with a hazard ratio of 2.6 (95% confidence interval 2.2-3.1; P < .0001). The risk of death increased according to the severity of the risk profile ranging from 0% (low risk) to 47% (high risk)., Conclusion: A simple score that includes a limited set of variables appears to be predictive of total mortality in an unselected real-world population undergoing ICD replacement. Evaluation of the patient's profile may assist in predicting vulnerability and should prompt individualized options, especially for high-risk patients., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The ECG Belt for CRT response trial is designed to test the hypothesis that in patients traditionally less likely to respond to cardiac resynchronization therapy (CRT), an individualized approach utilizing the electrocardiogram (ECG) Belt to guide lead placement, vector selection, and device programming is superior to current standard of care. The ECG Belt is a noninvasive mapping technology designed to measure beat by beat electrical activation of the left ventricle by utilizing unipolar measurements from multiple ECG electrodes on the body surface. The ECG Belt for CRT response trial is a multicenter, prospective, randomized, investigational pre-market research study conducted at 48 centers in the United States, Canada, and Europe and will randomize approximately 400 subjects. The trial has three arms (enrollment will be 2:1:1, respectively): utilization of the Belt to guide implant as well as postimplant programming, utilizing the Belt to guide postimplant programming alone, and a non-Belt control arm. AdaptivCRT will be an option in the treatment arm but not the control arms. The primary endpoint is change in left ventricular end-systolic volume between preimplant and at 6 months. This paper describes the design and analytic plan for the trial., (© 2020 Wiley Periodicals LLC.)

Background: Biventricular endocardial pacing (BiV ENDO) is a therapy for heart failure patients who cannot receive transvenous epicardial cardiac resynchronization therapy (CRT) or have not responded adequately to CRT. BiV ENDO CRT can be delivered by a new wireless LV ENDO pacing system (WiSE-CRT system; EBR Systems, Sunnyvale, CA), without the requirement for lifelong anticoagulation., Objective: The purpose of this study was to assess the safety and efficacy of the WiSE-CRT system during real-world clinical use in an international registry., Methods: Data were prospectively collected from 14 centers implanting the WiSE-CRT system as part of the WiCS-LV Post Market Surveillance Registry. (ClinicalTrials.gov Identifier: NCT02610673)., Results: Ninety patients from 14 European centers underwent implantation with the WiSE-CRT system. Patients were predominantly male, age 68.2 ± 10.5 years, left ventricular ejection fraction 30.6% ± 8.9%, mean QRS duration 180.7 ± 27.0 ms, and 40% with ischemic etiology. Successful implantation and delivery of BiV ENDO pacing was achieved in 94.4% of patients. Acute (<24 hours), 1- to 30-day, and 1- to 6-month complications rates were 4.4%, 18.8%, and 6.7%, respectively. Five deaths (5.6%) occurred within 6 months (3 procedure related). Seventy percent of patients had improvement in heart failure symptoms., Conclusion: BiV ENDO pacing with the WiSE-CRT system seems to be technically feasible, with a high success rate. Three procedural deaths occurred during the study. Procedural complications mandate adequate operator training and implantation at centers with immediately available cardiothoracic and vascular surgical support., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Early evidence suggests that multipoint left ventricular pacing (MPP) may improve response to cardiac resynchronization therapy (CRT). It is unknown whether this benefit is sustained and cost-effective. We used real-world data to evaluate long-term impact of MPP-ON clinical status, heart failure hospitalizations (HFH) and costs., Methods: The Italian registry on multipoint left ventricular pacing is a prospective, multicenter registry of patients implanted with MPP-enabled CRT devices. For this analysis, clinical and echocardiographic data were collected through 24 months and compared between patients with (MPP-ON) or without (MPP-OFF) early MPP activation at implant. The total cost of each HFH was estimated with national Italian reimbursement rates., Results: The study included 190 MPP-OFF and 128 MPP-ON patients with similar baseline characteristics. At 1 and 2 years, the MPP-ON group had lower rates of HFH vs MPP-OFF (1-year hazard ratio [HR]: 0.14, P = .0014; 2-year HR: 0.38, P = .009). The finding persisted in a subgroup of patients with consistent MPP activation through follow-up (1-year HR: 0.19; P = .0061; 2-year HR: 0.39, P = .022). Total HFH per-patient costs were lower in the MPP-ON vs the MPP-OFF group at 1 year (€101 ± 50 vs €698 ± 195, P < .001) and 2 years (€366 ± 149 vs €801 ± 203, P = .038). More MPP-ON patients had ≥5% improvement in ejection fraction (76.8% vs 65.4%, P = .025) and clinical composite score (66.7% vs 47.5%, P = .01)., Conclusions: In this multicenter clinical study, early MPP activation was associated with a significant reduction in cumulative HFH and related costs after 1 and 2 years of follow-up., (© 2020 Wiley Periodicals, Inc.)

Introduction: Atrial tachycardia/fibrillation (AT/AF) episodes are common in implantable cardioverter-defibrillator (ICD) recipients and can be undetected by standard single-chamber devices. This study aims to explore whether a single-lead ICD with an atrial dipole (ICD DX; BIOTRONIK SE & Co, Berlin, Germany) could improve the AT/AF diagnosis and management as compared to standard ICD (ICD VR)., Methods and Results: We selected patients without AT/AF history from the THINGS registry which included consecutive patients implanted with ICD for standard indications. The ICD VR and the ICD DX groups included 236 (62.8%) and 140 (37.2%) patients, respectively, and had no significant differences in baseline characteristics. During a median follow-up of 27 months, there were 7 AT/AF diagnoses in the ICD VR and 18 in the ICD DX group. The 2-year incidence of AT/AF diagnosis was 3.6% (95% confidence interval [CI]: 1.6%-9.6%) for the ICD VR and 11.4% (95% CI: 6.8%-18.9%) for the ICD DX group (adjusted hazard ratio [HR]: 3.85 [95% CI: 1.58-9.41]; P = .003). Initiation of oral anticoagulation (OAC) due to AT/AF diagnosis was reported in 15 patients. The 2-year incidence of OAC onset was 3.6% (95% CI: 1.6%-7.8%) for the ICD VR and 6.3% (95% CI: 3.0%-12.7%) for ICD DX group (adjusted HR: 1.99 [95% CI: 0.72-5.56]; P = .184)., Conclusion: We observed that atrial sensing capability in single-chamber ICD patients without evidence of atrial arrhythmias at implant is associated with a greater likelihood of detecting AT/AF episodes. The management of these diagnosed arrhythmias often led to clinical interventions, mainly represented by initiation of OAC therapy., (© 2020 Wiley Periodicals, Inc.)

Background: Multipoint pacing (MPP) may improve clinical outcomes in patients with cardiac resynchronization therapy defibrillators (CRT-D), but its impact on battery longevity in a real-world population has not been investigated in large trials., Objective: Compare projected battery longevity in CRT-D patients with and without MPP during long-term follow-up., Methods: The Italian registry on multipoint left ventricular pacing (IRON-MPP) is a prospective, multicenter registry of patients implanted with MPP-capable CRT-D devices. Projected battery longevity during follow-up was compared for patients with MPP (MPP ON) vs single-site (MPP OFF) left ventricular pacing at CRT-D implantation. A sub-analysis excluded crossover patients with MPP activation or deactivation occurring after implantation. A second sub-analysis excluded patients with a right or left ventricular pacing amplitude >2.5 V., Results: Out of 237 CRT-D patients (71 ± 9 years, 81% male) followed for 1.9 ± 0.8 years, 102 (43%) had MPP ON at implantation. Programmed atrial and ventricular outputs and percentage of pacing were similar between groups. MPP was associated with a 0.44 years reduction in projected battery longevity (P = .03) during long-term follow-up. Results were similar for the first and second sub-analyses, with a 0.57 years (P < .001) and 0.71 years (P < .001) reduction in projected longevity, respectively., Conclusion: In this long-term real-world registry, early MPP activation is associated with less than a 1-year reduction in projected battery life compared to single-site biventricular pacing., (© 2019 Wiley Periodicals, Inc.)

Aims: The benefit of prolonged implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy defibrillator (CRT-D) therapy following device replacement is hindered by clinical and procedure-related adverse events (AEs). Adverse events rate is highest in more complex devices and at upgrades, as per the REPLACE registry experience, but is changing owing to the improvement in device technology and medical care. We aimed at understanding the extent and type of AEs in a contemporary Italian population., Methods and Results: Detect long-term complications after ICD replacement (DECODE) was a prospective, single-arm, multicentre cohort study aimed at estimating medium- to long-term AEs in a large population of patients undergoing ICD/cardiac resynchronization defibrillator replacement/upgrade from 2013 to 2015. We prospectively analysed all clinical and device-related AEs at 12-month follow-up (FU) of 983 consecutive patients (median age 71 years, 76% male, 55% ischaemic, 47% CRT-D) followed for 353 ± 49 days. Seven percent of the patients died (60.6% for cardiovascular reasons), whereas 104 AEs occurred; 43 (4.4%) patients needed at least one surgical action to treat the AE. Adverse events rates were 3.3/100 years lead-related, 3.4/100 years bleedings, and 1.6/100 years infective. The primary endpoint was predicted by hospitalization in the month prior to the procedure [hazard ratio (HR) = 2.23, 1.16-4.29; 0.0169] and by upgrade (HR = 1.75, 1.02-2.99, 0.0441). One hundred and twelve (11.4%) patients met the combined endpoint of death from any cause, cardiac implantable electronic device (CIED)-related infection, and surgical action/hospitalization required to treat the AE. Hospitalization within 30 days prior to the procedure (HR = 2.07, 1.13-3.81; 0.0199), anticoagulation (HR = 1.97, 1.26-3.07; 0.003), and ischaemic cardiomyopathy (HR = 1.67, 95% confidence interval 1.06-2.63; P = 0.0276) were associated with the combined endpoint during FU., Conclusions: Adverse events following CIED replacement/upgrade are lower than previously reported, possibly owing to improved patients care. Hospitalization in the month prior to the procedure, upgrade, and clinical profile (anticoagulation, ischaemic cardiomyopathy) hint to increased risk, suggesting an individualized planning of the procedure to minimize overall AEs., Clinical Trial Registration: URL: http://clinicaltrials.gov/ Identifier: NCT02076789., (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: About one-third of patients receiving cardiac resynchronization therapy (CRT) are not responders, due to either patient selection or technical issues. Left ventricular quadripolar passive fixation leads (QPL) and bipolar active fixation (BAF) leads have been designed to ensure a targeted left ventricular stimulation area, minimizing lead dislodgments and phrenic nerve stimulation (PNS). The aim was to compare real-world safety and efficacy of BAF (Attain Stability, Medtronic Plc.) and QPL (Attain Performa, Medtronic Plc.)., Methods: We performed a retrospective analysis examining procedural and follow-up data of 261 BAF and 124 QPL (programmed to single-site left ventricular pacing), included in the ClinicalService project from 16 Italian hospitals., Results: At median follow-up of 12 months, no difference in left ventricular pacing threshold was recorded between BAF and QPL (1.3 ± 0.9 V @0.4 ms vs. 1.3 ± 1.0 V @0.4 ms; P = 0.749). Total left ventricular lead dislodgement rate was 1.43/100 patient-years in BAF vs. 2.9/100 patient-years in QPL (P = 0.583). However, no dislodgements occurred among BAF after hospital discharge. Events requiring repeated surgery or permanently turning CRT off occurred in 0.8% of BAF, as compared with 4.0% of QPL (P = 0.025). There was no difference between groups in the echo CRT responders' rate (70% of BAF and 66% of QPL; P = 0.589) or in the annual rate of heart failure hospitalization (P = 0.513)., Conclusions: BAF resulted in noninferior clinical outcome and CRT responders' rate in comparison to QPL. Moreover, BAF ensured more precise and stable placement in cardiac veins, with comparable electrical performance and less than 1% patients with unsolved PNS.

Aim: We carried out this study to investigate mid-term effects of cardiac resynchronization therapy (CRT) on right ventricular (RV) function and neurohormonal response, expressed by N-terminal pro-brain natriuretic peptide (NT-proBNP), in heart failure patients stratified by baseline RV ejection fraction (RVEF)., Methods and Results: Thirty-six patients with nonischemic dilated cardiomyopathy underwent technetium-99m radionuclide angiography with bicycle exercise immediately after CRT implantation (during spontaneous rhythm and after CRT activation) and 3 months later. Plasma NT proBNP was assessed before implantation and after 3 months. At baseline, RVEF was impaired (≤35%) in 14 patients, preserved (>35%) in 22. At 3 months, RVEF improved during rest and exercise (P = .02) in patients with impaired RV function, while remaining unchanged in patients with preserved RV function. Rest and exercise RV dyssynchrony decreased in both groups at follow-up (P < .05). A similar mid-term improvement in left ventricular (LV) function and NT-proBNP was observed in patients with impaired and preserved RVEF. In the former, the decrease in NT-proBNP correlated with the improvements both in LV and RV dyssynchrony and functions., Conclusion: CRT may improve RV performance, during rest and exercise, and neurohormonal response in heart failure patients with nonischemic dilated cardiomyopathy and baseline RV dysfunction. RV dysfunction should not be considered per se a primary criterion for excluding candidacy to CRT.

Chronic heart failure with reduced (≤ 40%) ejection fraction (HFrEF) poses a significant residual mortality risk despite modern optimal medical therapy. In the last decades, we have witnessed the introduction of breakthrough cardiac implantable electronic devices (CIED) aimed at addressing sudden cardiac death and HF progression in patients with HFrEF, leading to improved survival and functional capacity. Following their introduction, implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy (CRT) have undergone substantial technological improvements and have been investigated in different settings of HFrEF, some of which yielded controversial results. In this review, we provide a comprehensive, yet pragmatic, approach to the individual key points in the electrical manipulation of the failing heart with ICD and CRT including patient selection, technological advances in the implant technique, follow-up, and long-term management. The aim of the review is to provide real-life-oriented advices to maximize the desired outcomes of CIED-based therapy of HFrEF. Accordingly, a framework to inform the decision-making process in candidates to ICD and/or CRT has been developed reflective of a critical appraisal of the most recently available evidence reappraising some domains beyond the classic views.

Aim: To evaluate Attain Performa (Medtronic, Dublin, Ireland) quadripolar lead performance in clinical practice and, secondarily, to compare its long term clinical outcomes vs bipolar leads for left ventricular (LV) pacing., Methods and Results: We retrospectively analyzed clinical, procedural and follow-up data of 215 patients implanted with a quadripolar lead. One hundred and twenty one patients implanted with bipolar lead were selected to compare long-term clinical outcomes. The quadripolar lead was implanted in the target vein in 196 patients (91%) without acute dislodgements. In 50% of patients the chosen final pacing configuration at implant would not have been available with bipolar leads. A dedicated quadripolar pacing vector was chosen more frequently when the LV tip location was apical than otherwise (65.6% vs 42.7%, p=0.003). After a median follow-up of 14 months, the LV pacing threshold was less than 2.5V at 0.4ms in 98 patients (90%) with a safety margin between phrenic nerve and LV pacing threshold >3V in 97 patients (89%). We observed a slight trend toward a lower risk of heart failure worsening and a lower incidence of ventricular arrhythmias and pulmonary congestion in patients implanted with quadripolar leads compared with the control group., Conclusion: Quadripolar leads improve the management of phrenic nerve stimulation at no trade-off with pacing threshold and lead stability. Quadripolar leads seems to be associated with a lower incidence of VT/VF and pulmonary congestion, when compared with bipolar leads, but further investigations are necessary to confirm that this positive effect is associated with better LV reverse remodeling., (Copyright © 2018 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

We evaluated the performance of 3 different left ventricular leads (LV) for resynchronization therapy: bipolar (BL), quadripolar (QL) and active fixation leads (AFL). We enrolled 290 consecutive CRTD candidates implanted with BL (n = 136) or QL (n = 97) or AFL (n = 57). Over a minimum 10 months follow-up, we assessed: (a) composite technical endpoint (TE) (phrenic nerve stimulation at 8 V@0.4 ms, safety margin between myocardial and phrenic threshold <2V, LV dislodgement and failure to achieve the target pacing site), (b) composite clinical endpoint (CE) (death, hospitalization for heart failure, heart transplantation, lead extraction for infection), (c) reverse remodeling (RR) (reduction of end systolic volume >15%). Baseline characteristics of the 3 groups were similar. At follow-up the incidence of TE was 36.3%, 14.3% and 19.9% in BL, AFL and QL, respectively (p < 0.01). Moreover, the incidence of RR was 56%, 64% and 68% in BL, AFL and QL respectively (p = 0.02). There were no significant differences in CE (p = 0.380). On a multivariable analysis, "non-BL leads" was the single predictor of an improved clinical outcome. QL and AFL are superior to conventional BL by enhancing pacing of the target site: AFL through prevention of lead dislodgement while QL through improved management of phrenic nerve stimulation.

Objective: Cardiac resynchronisation therapy (CRT) is limited by a substantial proportion of non-responders. Left ventricular endocardial pacing (LVEP) may offer enhanced possibility to deliver CRT in patients with a failed attempt at implantation and to improve clinical status of CRT non-responders., Methods: The ALternate Site Cardiac ResYNChronisation (ALSYNC) study was a prospective, multi-centre cohort study that included 118 CRT patients with a successfully implanted endocardial left ventricular (LV) lead, including 90 failed coronary sinus (CS) implants and 28 prior non-responders who had worsened or unchanged heart failure status after at least 6 months of optimal conventional CRT therapy., Results: Patients were followed for 19 ± 9 months. At baseline, prior non-responders were sicker as evidenced by a larger LV end-diastolic diameter (70 ± 12 vs 65 ± 9 mm, p = .03) and a trend towards larger LV end-systolic volume index (LVESVi, 95 ± 51 vs 74 ± 39 ml/m 2 , p = .07), and were more frequently anti-coagulated (96% vs 72%, p = .008) despite similar history of atrial fibrillation (54% vs 51%, p = .83). At 6 months, LVEP significantly improved LV ejection fraction (2.3 ± 7.5 and 8.6 ± 10.0%), New York Heart Association Class (0.4 ± 0.9 and 0.7 ± 0.8), LVESVi (9 ± 16 and 18 ± 43 ml/m 2 ), and six-minute walk test (56 ± 73 and 54 ± 92 m) in prior non-responders and failed CS implants, relative to baseline (all p < .05), respectively. LVESVi reduction ≥15% was seen in 47% of the prior non-responder patients and 57% of failed CS patients., Conclusion: These data suggest that a sizable proportion of CRT non-responders can improve by LVEP, though to a lesser extent than failed CS implants. Clinical trial registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01277783., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Some barriers seem to exist in changing implantable cardioverter defibrillator (ICD) manufacturer at the time of device replacement. We sought to understand the obstacles to changing ICD manufacturer within the cohort of patients enrolled in the Detect Long-term Complications After ICD Replacement Registry., Methods: We analyzed 784 consecutive ICD/cardiac resynchronization therapy defibrillator (CRT-D) device replacements within a 1.5-year time-frame in 36 Italian centers to evaluate potential factors associated with changing manufacturers and system-related complications., Results: Manufacturer change occurred in 191 patients (24%): 72/211 single-chamber ICDs (34%), 52/210 dual-chamber ICDs (25%) and 67/363 CRT-D (18%, P < 0.0001 vs. single-chamber). Replacement-only procedures were associated with a lower rate of manufacturer change than upgrading procedures (23 vs. 32%, P = 0.02). In the single-chamber/dual-chamber cohort, the only variables associated with manufacturer change were the number of available manufacturers (OR = 1.9; P < 0.0001) and an upgrade procedure (OR = 1.7; P = 0.035), whereas the center volume was associated with maintenance of the same manufacturer (OR = 0.5; P = 0.0172). In the CRT-D group, the number of available manufacturers [OR = 2.9; P < 0.0001, service life below the median value (OR = 2.5; P = 0.0026)], and physiological design (OR = 8.4; P = 0.0048) were associated with manufacturer change. At 6-month follow-up, 17 patients (2.2%) experienced a system complication that was lead-related in all cases; upgrade procedure was the only predictor (hazard ratio = 6.7) of complications., Conclusion: At the time of ICD replacement, a manufacturer change occurred in 24% of patients and it was less likely in CRT-D devices, which are equipped with more specific technology and less frequently require the addition of features. System-related complications are strongly associated to upgrade procedures rather than to manufacturer change.

Aims: To evaluate if the increased thromboembolic risk in female patients may be related to a higher burden of atrial fibrillation (AF)., Methods and Results: Data collected in a prospective observational research of patients implanted with a cardiac implantable electrical device (CIED) were analysed. We included 2398 patients: 489 (20.4%) were female and 1909 (79.6%) were male (oral anticoagulants treatment in 23.2%, independent of gender). During the follow-up (mean 42.8, median 37.7 months), 26 thromboembolic events occurred in 22 patients, with an incidence rate ratio of both stroke and stroke/transient ischemic attack (TIA) significantly higher in females compared with males [2.00, 95% confidence interval (CI) 1.53-2.61, P< 0.001 for stroke; 1.77 (95% C1.37-2.31, P< 0.001 for stroke/TIA]. An AF burden ≥5 min was a common finding (44% of patients), with no difference between men and women. The maximum daily AF burden and the time to evolution in permanent AF did not differ according to gender. The results of multivariate Cox regression showed that female gender, as well as history of CABG, were significant independent predictors of stroke and female gender was also an independent predictor of stroke/TIA., Conclusions: Among patients implanted with a CIED, an AF burden of at least 5 min is a common finding, (44% of patients). Female patients have a risk of stroke and TIAs that is around two-fold that of male patients, but this increased risk cannot be ascribed to a higher burden of AF or to differences in the evolution to permanent AF., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01007474., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.)

Background: The impact on long-term outcomes of implantable cardioverter defibrillators (ICDs) and biventricular defibrillators for cardiac resynchronization (CRT-D) devices in 'real world' patients with heart failure (HF) needs to be assessed in terms of clinical effectiveness., Methods and Results: A registry including consecutive HF patients who underwent a first implant of an ICD (891 patients) or a CRT-D device (709 patients) in 2006-2010 was followed (median 1487 days and 1516 days, respectively), collecting administrative data on survival, all-cause hospitalizations, cardiovascular or HF hospitalizations, and days alive and out of hospital (DAOH). Survival free from death/cardiac transplant was 61.9% and 63.8% at 5 years for ICD and CRT-D patients, respectively. Associated comorbidities (Charlson Comorbidity Index) had a significant impact on death/cardiac transplant, as well as on hospitalizations. The median values of DAOH% were 97.4% for ICD and 97.7% for CRT-D patients, but data were highly skewed, with the lower quartile of DAOH% values including values ranging between 0% and 52.8% for ICD and between 0% and 56.1% for CRT-D patients. Charlson Comorbidity Index was a very strong predictor of DAOH%., Conclusions: Patients who were implanted in 'real world' clinical practice with an ICD or a CRT-D device have, on average, a relatively favourable outcome, with a survival of around 62-64% at 5 years, but with an important burden of hospitalizations. Comorbidities, as evaluated by means of the Charlson Comorbidity Index, have a significant impact on outcomes in terms of mortality/heart transplant, hospitalizations and days spent alive and out of hospital., (© 2016 The Authors European Journal of Heart Failure © 2016 European Society of Cardiology.)

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is used in patients at risk of sudden death. Our aim was to assess clinical predictors of electrocardiographic ineligibility for S-ICD, and the impact of exercise on S-ICD eligibility in an unselected series of patients requiring ICD therapy., Methods: 102 patients at risk of sudden death were evaluated at rest and during exercise. Electrocardiograph screening using limb lead electrodes (to simulate the S-ICD sensing vectors) was performed at rest and during bicycle ergometer exercise., Results: R wave amplitude in lead D3 during exercise >16mV, baseline QTc and the sum of amplitudes of the R waves at supine >30mV were predictors of ineligibility for S-ICD. Eligibility increased from 90% to 100% of patients when evaluated with an "any of the three leads" criterion compared to current recommendations. A more restrictive criterion based on two of three ECG leads caused an eligibility drop at 66%, that further decreased to 56% during exercise; these figures improved to 79% and 81%, respectively, when an "any 2 of 3 leads" criterion was used., Conclusions: Huge ECG amplitude and QTc duration are associated with ineligibility in the current S-ICD release. By performing exercise testing, lead suitability changes in one patient out of 14 (7% of tested patients) and eligibility is decreased by use of a more stringent criterion for eligibility (ECG criteria satisfied in two of three leads). A dynamic selection of sensing vectors aiming at situation-specific suitability (any of three leads) would increase S-ICD eligibility to 100% of patients., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Aim: Cardiac resynchronization is a well tolerated and effective therapy for heart failure, but 30% of patients still do not respond to biventricular pacing. Optimization of device settings, in particular interventricular delay value, represents a plausible target for improving these results, but available literature is discordant. We aimed our study at the identification of the best suitable candidates to interventricular delay optimization., Methods: A total of 77 consecutive patients with optimized drugs therapy underwent clinical, echocardiographic and electrocardiographic evaluation before and after 6 months from implantation of a biventricular defibrillator in accordance to current guidelines. In each patient, atrioventricular and interventricular delay values were optimized at predischarge with echocardiogram., Results: The only predictor of an optimized interventricular delay value different from simultaneous (i.e. standard shipment setting), at both univariate and multivariate analyses, was a QRS duration greater than 160 ms (odds ratio 22.958; P = 0.003) with a sensitivity of 70.9%., Conclusion: Candidates to cardiac resynchronization therapy with a basal QRS greater than 160 ms have a higher chance of requiring echo-guided tailoring of interventricular delay value. A strategy based on these data can potentially improve device programming, reducing by one-third the need for optimization, according to our findings, and at the same time avoid unnecessary time-consuming procedures.

The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) trial, published in April 2013 [Curtis AB, Worley SJ, Adamson PB, et al; Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) Trial Investigators. Biventricular pacing for atrioventricular block and systolic dysfunction. N Engl J Med 2013; 368:1585-1593], explored whether cardiac resynchronization therapy (CRT) was superior to conventional pacing in patients with conventional indications for pacing, left ventricular dysfunction and NYHA (New York Heart Association) class I-III. The trial took 8 years and a source of concern is selection bias, because participating centers had an average of two patients enrolled per center, per year. Both the internal and external validity of the trial merit some comments. BLOCK HF showed a relatively low treatment effect of CRT as compared with other CRT trials. As a matter of fact, the absolute risk reduction for death or hospitalization because of heart failure was 4.8%, in a relatively long follow-up, with a number needed to treat (NNT) of 21, much higher than the NNT of other CRT trials. We estimate that at least one third of patients in BLOCK HF could meet current indications for CRT. Moreover, the study did not consider the additional risks and costs of CRT versus conventional pacing, both having important implications for cost-effectiveness estimates. For these and other reasons, uncertainties arise as to how far BLOCK HF extends current recommendations for CRT and how much it should be implemented in daily clinical practice.

Background: To understand the impact of a quadripolar left ventricular (LV) lead on reverse remodeling and phrenic nerve stimulation (PNS) in congestive heart failure patients treated by cardiac resynchronization therapy at 8-month follow-up (FU)., Methods: One hundred and fifty-eight patients received an LV Medtronic Performa lead (Medtronic Inc., Minneapolis, MN, USA) and were reevaluated at FU by echocardiography and measurement of electrical parameters., Results: A targeted LV lead placement was achieved in 140 (89%) patients. Super responders and responders were 76 (50%) and 26 (18%), respectively, at FU; seven (4%) died and 13 (8%) were hospitalized for any cause. Nonischemic etiology was the only independent predictor of reverse remodeling. The configurations available only with the Performa leads reduced PNS occurrence at 8 V@0.4 ms from 43 (27%) to 14 (9%) of patients at implantation, and from 44 (28%) to 19 (12%) at last FU, compared to configurations available with bipolar leads. Patients with detectable PNS had >10/16 pacing configurations with a PNS safety margin >2 V both at implantation and at FU. During FU 16 (10%) patients had an adverse event possibly related to the lead or to modification of the underlying heart disease but 99% of these events were fixed by reprogramming of the pacing vector., Conclusions: Performa Lead enables an increased capability to achieve a targeted lead positioning in the broad clinical scenario of large- and small-volume implanting centers, with a relevant impact on the occurrence of reverse remodeling compared to literature data. The enhanced management of PNS resulted in a dislodgement rate of only 1%., (© 2015 Wiley Periodicals, Inc.)

Background: Cardiac resynchronization therapy (CRT) is an established therapy for advanced congestive heart failure, improving both survival and hospitalization. The mechanism beneath these improvements still needs to be defined as about one-third of the patients do not benefit from resynchronization. Restoration of sympatho-vagal function can play a significant role in the process, but available data are limited. In this scenario, positron emission tomography scans with (11) C-hydroxyephedrine, a noradrenaline analogous, has the potential to characterize the modifications of the sympathetic nervous system induced by CRT in decompensated patients., Materials and Methods: Ten patients (six males, age 68 ± 10 years) with primary dilated cardiomyopathy were studied before and after resynchronization (acutely and after 3 months), from a clinical and echocardiographic point of view. Their cardiac sympathetic nerve activity was evaluated by (11) C-hydroxyephedrine positron emission tomography before resynchronization, at short and medium term after resynchronization., Results: Responders to CRT (patients showing ≥ 15% decrease in left ventricular end-systolic volume) showed a higher level of left ventricular radiotracer uptake both at baseline and after resynchronization with respect to nonresponders. This was coupled with a progressive improvement in homogeneity in left ventricular tracer uptake mainly in responders., Conclusions: Cardiac resynchronization therapy improves cardiac sympathetic nerve activity in responders since its activation, while nonresponders do not show any significant change at any time of evaluation. CRT seems to be more effective in those patients with a still structurally preserved, yet functionally impaired, neuroautonomic system., (© 2015 Stichting European Society for Clinical Investigation Journal Foundation.)

Non-response to cardiac resynchronization therapy remains a significant problem in up to 30% of patients. Multisite stimulation has emerged as a way of potentially overcoming non-response. This may be achieved by the use of multiple leads placed within the coronary sinus and its tributaries (dual-vein pacing) or more recently by the use of multipolar (quadripolar) left ventricular pacing leads which can deliver pacing stimuli at multiple sites within the same vein. This review covers the role of multisite pacing including the interaction with the underlying pathophysiology, the current and planned studies, and the potential pitfalls of this technology., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aims: Left ventricular (LV) lead dislodgement occurs in about 10.6% of patients in the first 12 months after cardiac resynchronization therapy defibrillator implantation, and causes lack of clinical improvement, repeated surgery, and predisposes to infective complications and death. To understand the factors predictive of lead dislodgement, and to investigate whether bipolar LV lead stabilization can reduce the dislodgement rate and improve the clinical outcome., Methods and Results: Predisposing coronary vein anatomy was identified on a retrospective series of 218 patients implanted before August 2009. Lead stabilization guided by vein anatomy was prospectively tested on consecutive patients from October 2009 to December 2010. Among 84 patients, lead stabilization based on vein anatomy was recommended in 19 patients, of which 16 agreed and 3 refused. Two of these latter had lead dislodgement within 1 month, whereas none of the former had adverse events during 23.8 ± 3.1 months follow-up. Only 1 of 58 patients deemed at low risk had lead dislodgement. Seven patients required lead stabilization for severe phrenic stimulation issues that dictated lead placement at specific sites. Patients with stabilized LV leads were more likely to be cardiac resynchronization therapy (CRT) responders than the others: 19 of 26 (73%) vs. 34 of 58 (59%, P= NS), and had a significantly higher proportion of super-responders: 12 of 26 (46%) vs. 12 of 58 (21%, P< 0.005)., Conclusion: Coronary vein anatomy may assist decision making about the need for LV lead stabilization, and the choice of tools during the implanting procedure to ensure effective CRT delivery at long term.

Background: Consensus guidelines define indications for cardiac resynchronization therapy (CRT), but the variability in implant rates in 'real world' clinical practice, as well as the relationship with the epidemiology of heart failure are not defined., Methods and Results: In Emilia-Romagna, an Italian region with around 4.4 million inhabitants, a registry was instituted to collect data on implanted devices for CRT, with (CRT-D) or without defibrillation (CRT-P) capabilities. Data from all consecutive patients resident in this region who underwent a first implant of a CRT device in years 2006-2010 were collected and standardized (considering each of the nine provinces of the region). The number of CRT implants increased progressively, with a 71% increase in 2010 compared to 2006. Between 84 and 90% of implants were with CRT-D devices. The variability in standardized implant rates among the provinces was substantial and the ratio between the provinces with the highest and the lowest implant rates was always greater than 2. Considering prevalent cases of heart failure in the period 2006-2010, the proportion of patients implanted with CRT per year ranged between 0.23 and 0.30%., Conclusions: The application in 'real world' clinical practice of CRT in heart failure is quite heterogeneous, with substantial variability even among areas belonging to the same region, with the need to make the access to this treatment more equitable. Despite the increased use of CRT, its overall rate of adoption is low, if a population of prevalent heart failure patients is selected on the basis of administrative data on hospitalizations.

Aims: Unwanted phrenic nerve stimulation (PNS) has been reported in ∼1 in 4 patients undergoing left ventricular (LV) pacing. The occurrence of PNS over mid-term follow-up and the significance of PNS are less certain., Methods and Results: Data from 1307 patients enrolled in pre-market studies of LV leads manufactured by Medtronic (models 4193 and 4195 unipolar, 4194, 4196, 4296, and 4396 bipolar) were pooled. Left ventricular lead location was recorded at implant using a common classification scheme. Phrenic nerve stimulation symptoms were either spontaneously reported or identified at scheduled follow-up visits. A PNS-related complication was defined as PNS resulting in invasive intervention or the termination of LV pacing. Average follow-up was 14.9 months (range 0.0-46.6). Phrenic nerve stimulation symptoms occurred in 169 patients (12.9%). Phrenic nerve stimulation-related complications occurred in 21 of 1307 patients (1.6%); 16 of 738 (2.2%) in the unipolar lead studies, and 5 of 569 (0.9%) in the bipolar lead studies (P = 0.08). Phrenic nerve stimulation was more frequent at middle-lateral/posterior, and apical LV sites (139/1010) vs. basal-posterior/lateral/anterior, and middle-anterior sites (20/297; P= 0.01). As compared with an anterior LV lead position, a lateral LV pacing site was associated with over a four-fold higher risk of PNS (P= 0.005) and an apical LV pacing site was associated with over six-fold higher risk of PNS (P= 0.001)., Conclusion: Phrenic nerve stimulation occurred in 13% of patients undergoing LV lead placement and was more common at mid-lateral/posterior, and LV apical sites. Most cases (123/139; 88%) of PNS were mitigated via electrical reprogramming, without the need for invasive intervention.