Search

Aims: Cardiac resynchronization therapy (CRT) is indicated in patients with heart failure and bundle branch block. It is less clear whether this includes patients with pre-existing right ventricular pacemaker/defibrillator systems, particularly with respect to implantation success and clinical benefit. [ABSTRACT FROM PUBLISHER]

Aims: Suboptimal device programming is frequent in non-responders to cardiac resynchronization therapy (CRT). However, the role of device optimization and the most appropriate technique are still unknown. The aim of our study was to analyse the effect of different CRT optimization techniques within a network meta-analysis., Methods: A systematic search was conducted on MEDLINE, Embase and CENTRAL for studies comparing outcomes with empirical device settings or optimization using echocardiography, static algorithms or dynamic algorithms. Studies investigating the effect of optimization in non-responders were also analysed., Results: A total of 17 studies with 4346 patients were included in the quantitative analysis. Of the treatments and outcomes examined, a significant difference was found only between dynamic algorithms and echocardiography, with the former leading to a higher echocardiographic response rate [odds ratio (OR): 2.02, 95% confidence interval (CI) 1.21-3.35], lower heart failure hospitalization rate (OR: 0.75, 95% CI 0.57-0.99) and greater improvement in 6-minute walk test [mean difference (MD): 45.52 m, 95% credible interval (CrI) 3.91-82.44 m]. We found no significant difference between empirical settings, static algorithms and dynamic algorithms. Seven studies with 228 patients reported response rates after optimization in non-responders. Altogether, 34.3%-66.7% of initial non-responders showed improvement after optimization, depending on response criteria., Conclusions: At the time of CRT implantation, dynamic algorithms may serve as a resource-friendly alternative to echocardiographic optimization, with similar or better mid-term outcomes. However, their superiority over empirical device settings needs to be investigated in further trials. For non-responders, CRT optimization should be considered, as the majority of patients experience improvement., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation) demonstrated that apixaban, compared with aspirin, significantly reduced stroke and systemic embolism (SE) but increased major bleeding in patients with subclinical atrial fibrillation., Objectives: To help inform decision making, the authors evaluated the efficacy and safety of apixaban according to baseline CHA 2 DS 2 -VASc score., Methods: We performed a subgroup analysis according to baseline CHA 2 DS 2 -VASc score and assessed both the relative and absolute differences in stroke/SE and major bleeding., Results: Baseline CHA 2 DS 2 -VASc scores were <4 in 1,578 (39.4%) patients, 4 in 1,349 (33.6%), and >4 in 1,085 (27.0%). For patients with CHA 2 DS 2 -VASc >4, the rate of stroke was 0.98%/year with apixaban and 2.25%/year with aspirin; compared with aspirin, apixaban prevented 1.28 (95% CI: 0.43-2.12) strokes/SE per 100 patient-years and caused 0.68 (95% CI: -0.23 to 1.57) major bleeds. For CHA 2 DS 2 -VASc <4, the stroke/SE rate was 0.85%/year with apixaban and 0.97%/year with aspirin. Apixaban prevented 0.12 (95% CI: -0.38 to 0.62) strokes/SE per 100 patient-years and caused 0.33 (95% CI: -0.27 to 0.92) major bleeds. For patients with CHA 2 DS 2 -VASc =4, apixaban prevented 0.32 (95% CI: -0.16 to 0.79) strokes/SE per 100 patient-years and caused 0.28 (95% CI: -0.30 to 0.86) major bleeds., Conclusions: One in 4 patients in ARTESiA with subclinical atrial fibrillation had a CHA 2 DS 2 -VASc score >4 and a stroke/SE risk of 2.2% per year. For these patients, the benefits of treatment with apixaban in preventing stroke/SE are greater than the risks. The opposite is true for patients with CHA 2 DS 2 -VASc score <4. A substantial intermediate group (CHA 2 DS 2 -VASc =4) exists in which patient preferences will inform treatment decisions. (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; NCT01938248)., Competing Interests: Funding Support and Author Disclosures The ARTESiA study was funded by grants from the Canadian Institutes of Health Research (201610PTJ-378238), the Bristol Myers Squibb–Pfizer Alliance, the Heart and Stroke Foundation of Canada, the Canadian Stroke Prevention Intervention Network, Hamilton Health Sciences, the Accelerating Clinical Trials Network, the Population Health Research Institute, and Medtronic. The sponsors had no role in data analysis, interpretation, or publication. Dr Lopes has received research grants from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Novo Nordisk, Pfizer, and Sanofi US Services Inc; and has served as a consultant to Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo Company, GlaxoSmithKline, Medtronic, Merck, Novo Nordisk, Pfizer, Portola Pharmaceuticals, and Sanofi US Services Inc. Dr Granger has received research grants from Bayer and Boehringer Ingelheim; and has served as a consultant to Anthos, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific Corporation, Bristol Myers Squibb, Cadrenal, Daiichi-Sankyo Company, Janssen Global Services, LLC, Merck, Pfizer Inc, and Tenac.io. Dr McIntyre has served as a consultant to Servier Pharmaceuticals LLC. Dr Rivard has received research grants from Bayer Inc, Heart and Stroke Foundation, Canadian Institutes of Health Research (CIHR), and FRQS (Fonds de Recherche Quebec-Sante). Dr Atar has received speaker fees from Amgen, Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Philips, Roche Diagnostics, Sanofi, Takeda, and Vifor; and has received institutional grant support from Bristol Myers Squibb/Pfizer, Medtronic, Bayer, and Roche Diagnostics. Dr Boriani has received speaker fees from Bayer, Boston Scientific, Boehringer Ingelheim, Daiichi-Sankyo, Janssen, and Sanofi. Dr Duray has served as a consultant to Medtronic and Biotronik. Dr Gold has received institutional research support from Abbott, Boston Scientific, and Medtronic; and has received consulting fees from Boston Scientific and Medtronic. Dr Hohnloser has served as a consultant to Pfizer, Bristol Myers Squibb, Boehringer Ingelheim, and Sanofi. Dr Kutyifa has received research grants from Boston Scientific, ZOLL, National Institutes of Health, and Spire Inc; has received speaker fees from Medtronic, Abbott, and Biotronik; and has received consultant fees from Biotronik. Dr Sticherling has served as a consultant to Medtronic, Boston Scientific, and Biotronik. Dr Benz has received lecture fees from Bristol Myers Squibb and AstraZeneca; and has participated in an educational program supported by Boston Scientific (“Fellowship Herzrhythmus”). Dr Linde has received research support from the Swedish Heart Lung Foundation, Swedish Royal Society of Science, and Stockholm County Council; has received consulting fees from AstraZeneca and Roche Diagnostics; has received speaker honoraria from Novartis, AstraZeneca, Bayer, Vifor Pharma, Medtronic, and Impulse Dynamics; and has served on advisory boards for Astra Zeneca. Dr Kautzner has served as a consultant for Abbott Vascular, Biotronik, Boston Scientific Corporation, GE Healthcare, and Medtronic, Inc. Dr Mairesse has received consultant or speaker fees from Abbott, Biotronik, Microport, Bristol Myers Squibb/Pfizer, and Daiichi-Sankyo. Dr Connolly has received research grants from Pfizer Inc; and has served as a consultant for Bayer, Bristol Myers Squibb, Daiichi-Sankyo Company, and Javelin Ventures. Dr Healey has received research grants from Boston Scientific Corporation, Bristol Myers Squibb, Medtronic, and Pfizer; has served as a consultant for Bayer, Boston Scientific Corporation, Medtronic, Novartis, and Servier Affaires Medicales; and has served as an expert witness for Bayer., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

(1) Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). (2) Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed-up for a mean 37 months ± 28 months. Digitalis use was assessed at the time of CRT implantation. A multivariate Cox-regression model and propensity score matching were used to determine all-cause mortality as the primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%) and incidence of ICD shocks and rehospitalization were assessed as secondary endpoints in a subgroup of patients. (3) Results: The study comprised 552 CRT-recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and a higher NYHA class (all p ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR = 1.14; 95% CI 0.88-1.5; p = 0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR = 1.04; 95% CI 0.75-1.45; p = 0.82). Furthermore, in comparison to 286 propensity-score-matched patients, mortality was not affected by digitalis intake (propensity-adjusted HR = 1.11; 95% CI 0.72-1.70; p = 0.64). A CRT-response was predominant in digitalis non-users, concerning both improvement of HF symptoms and LVEF (NYHA p < 0.01; LVEF p < 0.01), while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock ( p = 0.01); although, rehospitalization for cardiac reasons was significantly lower among digitalis users compared to digitalis non-users (HR = 0.58; 95% C. I. 0.40-0.85; p = 0.01). (4) Conclusions: Digitalis therapy had no effect on mortality, but was associated with a reduced response to CRT and increased susceptibility to ventricular arrhythmias requiring ICD shock treatment. Although, digitalis administration positively altered the likelihood for cardiac rehospitalization during follow-up.

Background: Kidney dysfunction (KD) is a main limiting factor of applying guideline-directed medical therapy (GDMT) and reaching the recommended target doses (TD) in heart failure (HF) with reduced ejection fraction (HFrEF)., Hypothesis: We aimed to assess the success of optimization, long-term applicability, and adherence of neurohormonal antagonist triple therapy (TT:RASi [ACEi/ARB/ARNI] + βB + MRA) according to the KD after a HF hospitalization and to investigate its impact on prognosis., Methods: The data of 247 real-world, consecutive patients were analyzed who were hospitalized in 2019-2021 for HFrEF and then were followed-up for 1 year. The application and the ratio of reached TD of TT at hospital discharge and at 1 year were assessed comparing KD categories (eGFR: ≥90, 60-89, 45-59, 30-44, <30 mL/min/1.73 m 2 ). Moreover, 1-year all-cause mortality and rehospitalization rates in KD subgroups were investigated., Results: Majority of the patients received TT at hospital discharge (77%) and at 1 year (73%). More severe KD led to a lower application ratio (p < .05) of TT (92%, 88%, 80%, 73%, 31%) at discharge and at 1 year (81%, 76%, 76%, 68%, 40%). Patients with more severe KD were less likely (p < .05) to receive TD of MRA (81%, 68%, 78%, 61%, 52%) at discharge and a RASi (53%, 49%, 45%, 21%, 27%) at 1 year. One-year all-cause mortality (14%, 15%, 16%, 33%, 48%, p < .001), the ratio of all-cause rehospitalizations (30%, 35%, 40%, 43%, 52%, p = .028), and rehospitalizations for HF (8%, 13%, 18%, 20%, 38%, p = .001) were significantly higher in more severe KD categories., Conclusions: KD unfavorably affects the application of TT in HFrEF, however poorer mortality and rehospitalization rates among them highlight the role of the conscious implementation and up-titration of GDMT., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

(1) Background: Besides the use of guideline-directed medical therapy (GDMT), multidisciplinary heart failure (HF) outpatient care (HFOC) is of strategic importance in HFrEF. (2) Methods: Data from 257 hospitalised HFrEF patients between 2019 and 2021 were retrospectively analysed. Application and target doses of GDMT were compared between HFOC and non-HFOC patients at discharge and at 1 year. 1-year all-cause mortality (ACM) and rehospitalisation (ACH) rates were compared using the Cox proportional hazard model. The effect of HFOC on GDMT and on prognosis after propensity score matching (PSM) of 168 patients and the independent predictors of 1-year ACM and ACH were also evaluated. (3) Results: At 1 year, the application of RASi, MRA and triple therapy (TT: RASi + βB + MRA) was higher ( p < 0.05) in the HFOC group, as was the proportion of target doses of ARNI, βB, MRA and TT. After PSM, the composite of 1-year ACM or ACH was more favourable with HFOC (propensity-adjusted HR = 0.625, 95% CI = 0.401-0.974, p = 0.038). Independent predictors of 1-year ACM were age, systolic blood pressure, application of TT and HFOC, while 1-year ACH was influenced by the application of TT. (4) Conclusions: HFOC may positively impact GDMT use and prognosis in HFrEF even within the first year of its initiation.

Introduction: Renal dysfunction is a main limiting factor of applying and up-titrating guideline-directed medical therapy (GDMT) among patients with heart failure with reduced ejection fraction (HFrEF)., Objective: Our retrospective monocentric observational study aimed to analyse the application ratio of combined neurohormonal antagonist therapy (RASi: ACEI/ARB/ARNI + βB + MRA) and 12-month all-cause mortality differences in terms of renal dysfunction among HFrEF patients hospitalized for heart failure., Method: We retrospectively analysed the cohort of consecutive HFrEF patients, hospitalized at the Heart Failure Unit of our tertiary cardiological centre in 2019-2021. The application ratio of discharge triple therapy (TT) in five groups established on admission eGFR parameters, representing severity of renal dysfunction (eGFR≥90, eGFR = 60-89, eGFR = 45-59, eGFR = 30-44, eGFR<30 ml/min/1.73 m2) was investigated with chi-square test, while 12-month mortality differences were analysed with Kaplan-Meier method and log-rank test., Results: 257 patients were included. Median eGFR was 57 (39-75) ml/min/1.73 m2, 54% of patients had eGFR<60 ml/min/1.73 m2. The proportion of patients in eGFR≥90, 60-89, 45-59, 30-44, <30 ml/min/1.73 m2 subgroups was 12%, 34%, 18%, 21%, 15%, respectively. 2% of patients were on dialysis. Even though the application rate of TT was notably high (77%) in the total cohort, more severe renal dysfunction led to a significantly lower implementation rate of TT (94%, 86%, 91%, 70%, 34%; p<0.0001): the application rate of RASi (100%, 98%, 96%, 89%, 50%, p<0.0001), βB (94%, 88%, 96%, 79%, 68%; p = 0.003) and MRA therapy (97%, 99%, 98%, 94%, 82%; p = 0.001) differed significantly. 12-month all-cause mortality was 23% in the whole cohort. Mortality rates were higher in more severe renal dysfunction (3%, 15%, 22%, 31%, 46%; p<0.0001)., Conclusion: Even though the proportion of patients on TT in the whole cohort was remarkably high, renal dysfunction led to a significantly lower application ratio of TT, associating with worse survival. Our results highlight that despite renal dysfunction the application of HFrEF cornerstone pharmacotherapy is essential. Orv Hetil. 2023; 164(35): 1387-1396.

Introduction: Hospitalization due to heart failure (HF) progression is associated with poor prognosis. This highlights the role of the implementation of guideline-directed medical therapy (GDMT) in improving the morbidity and mortality of patients with heart failure with reduced ejection fraction (HFrEF). There are limited data about the intrahospital applicability of GDMT in real-world circumstances. We aimed to assess retrospectively the use of cornerstone GDMT including RASi (ACEI/ARB/ARNI), βB, MRA, and SGLT2i treatment in a consecutive real-world HFrEF patient population admitted with signs and symptoms of HF to the HF Unit of a Hungarian tertiary cardiac center between 2019 and 2021. The independent predictors of therapy optimization and the applicability of new HFrEF medication (ARNI, SGLT2i, vericiguat) were also investigated., Methods: Statistical comparison of admission and discharge medication was accomplished with Fisher's exact test. The independent predictors of the introduction of triple therapy (RASi + βB + MRA) were analyzed using univariate and multivariate logistic regression. The proportion of patients eligible for vericiguat based on the inclusion and exclusion criteria of the VICTORIA trial was also investigated, as well as the number of patients suitable for ARNI and SGLT2i, taking into account the contraindications of application contained in the ESC 2021 HF Guidelines., Results: 238 patients were included. During hospitalization, the use of RASi (69% vs. 89%) (ACEI/ARBs [58% vs. 70%], ARNI [10% vs. 19%]), βBs (69% vs. 85%), and MRAs (61% vs. 95%) increased significantly (p < 0.05) compared to at admission, and the use of SGLT2i (3% vs. 11%) also rose (p = 0.0005). The application ratio of triple (RASi + βB + MRA; 43% vs. 77%) and quadruple (RASi + βB + MRA + SGLT2i; 2% vs. 11%) therapy increased as well (p < 0.0001). The independent predictors of discharge application of triple therapy revealed through multivariate logistic regression analysis were age, duration of hospitalization, eGFR, NTproBNP, and presence of diabetes mellitus. Sixty-eight percent of the cohort would have been suitable for vericiguat, 83% for ARNI, and 84% for SGLT2i., Conclusion: High rates of application of disease-modifying drugs are achievable among hospitalized HFrEF patients in severe clinical condition; thus, awareness of the need for their initiation must be raised., (© 2022 S. Karger AG, Basel.)

Cardiac resynchronization therapy (CRT) may improve not only impaired left ventricular contractility but can also induce reverse remodeling of native conduction system. Measurement of intrinsic QRS complex width during follow-up is the simplest method to assess reverse electrical remodeling (RER). We aimed to provide a literature review and meta-analysis on incidence and impact of RER and its association with mechanical remodeling. A systematic review and random-effect meta-analysis of studies reporting data on RER was performed. A total of 16 studies were included in this meta-analysis with 930 patients undergoing CRT (mean age 64.0 years, 64.1% males). The weighted mean incidence of RER was 42%. Reverse mechanical remodeling assessed by echocardiography was more frequently observed in patients with RER compared to patients without RER (75.7% vs. 46.6%; odds ratio [OR] 3.7, 95% confidence interval [CI] 2.24-6.09, p &lt; 0.01). Mechanical responders had a mean iQRS shortening of 7.7 ms, while mechanical non-responders experienced a mean widening of iQRS by 5.2 ms (p &lt; 0.01). Clinical improvement was more frequent in patients with RER vs. patients without RER (82.9% vs. 49.0%; OR 5.26; 95% CI 2.92-9.48; p &lt; 0.01). No significant difference in all-cause mortality between patients with and without RER was found. Mean difference between baseline intrinsic QRS and post-implantation paced QRS was significant in patients with later RER (21.2 ms, 95% CI 9.4-32.9, p &lt; 0.01), but not in patients without RER (6.6 ms, 95% CI -2.2-15.4, p = 0.14). Gender, initial left bundle block morphology and heart failure etiology were found not to be predictive for RER. Our meta-analysis demonstrates that shortening of iQRS duration is a common finding during follow-up of patients undergoing CRT and is associated with mechanical reverse remodeling and clinical improvement. Clinical Trial Registration: Prospero Database-CRD42021253336., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cardiac implantable electronic devices establish proper therapy for the prevention of sudden cardiac death, significantly reducing the morbidity and mortality of patients with arrhythmias and heart failure. It is well-known that the number of electrodes increases the risk of complications. To preserve the benefit of atrial sensing without the need to implant an additional lead, a single-lead ICD system with a floating atrial dipole (DX ICD lead) has been developed. Besides all of the potential benefits, the necessity of a reliable and stable atrial sensing via the floating dipole could be the main concern against the use of this lead type. In the current generation of DX devices, the specially filtered atrial signal seems to be high enough and stable over time, which is crucial in the early detection of atrial arrhythmias, discrimination between different forms of tachycardias in order to prevent inappropriate ICD therapy, and achieving an optimal atrioventricular and interventricular synchrony in patients with a two-lead CRT-DX system. The present review summarizes the benefits and potential drawbacks of the DX ICD systems based on the available literature, furthermore, proposes an evidence-based algorithm of ICD type selection., Competing Interests: Declaration of Competing Interest M. V. reports consulting/lecture fees and/or nonfinancial support from Abbott, Bayer, Biotronik, Daiichi Sankyo, Egis, Minimal lnvasive Technology Ltd., and Sanofi-Aventis. M. N. reports consulting/lecture fees and/or nonfinancial support from Biotronik, Boston Scientific, Egis, MicroPort, and Medtronic. T.B. is an employee of Biotronik Hungary Ltd. E. Z. reports consultancy/speaker/advisory board fees and/or nonfinancial support from Abbott, Amomed, Bayer, Biotronik, Boston Scientific, Innomed, Orion, Pfizer, Replant, and Richter. G. Z. D. reports consulting/lecture fees and/or nonfinancial support from Abbott, Biotronik, Daiichi Sankyo, Medtronic, MSD, Replant, Richter, Pfizer, and Sanofi., (Copyright © 2021. Published by Elsevier Inc.)

Aims: This study aims to characterize the range of implantable device-based sensor values including heart sounds, markers of ventilation, thoracic impedance, activity, and heart rate for patients with heart failure (HF) when patients were deemed to be in clinically stable periods against the time course of acute decompensation and recovery from HF events., Methods and Results: The MultiSENSE trial followed 900 patients implanted with a COGNIS CRT-D for up to 1 year. Chronic, ambulatory diagnostic sensor data were collected and evaluated during clinically stable periods (CSP: unchanged NYHA classification, no adverse events, and weight change ≤2.27 kg), and in the timeframe leading up to and following HF events (HF admissions or unscheduled visits with intravenous HF treatment). Physiologic sensor data from 1667 CSPs occurring in 676 patients were compared with those data leading up to and following 192 HF events in 106 patients. Overall, the mean age was 66.6 years, and the population were predominantly male (73%). Patients were primarily in NYHA II (67%), with a mean LVEF of 29.6% and median NT-proBNP of 754.5 pg/mL. Sensor values during CSP were poorer in patients who had HF events during the study period than those without HF events, including first heart sound (S1: 2.18 ± 0.84 mG vs. 2.62 ± 0.95 mG, P = 0.002), third heart sound (S3: 1.13 ± 0.36 mG vs. 0.91 ± 0.30 mG, P < 0.001), thoracic impedance (45.66 ± 8.78 Ohm vs. 50.33 ± 8.43 Ohm, P < 0.001), respiratory rate (19.09 ± 3.10 br/min vs. 17.66 ± 2.39 br/min, P = 0.002), night time heart rate (73.39 ± 8.36 b.p.m. vs. 69.56 ± 8.09 b.p.m., P = 0.001), patient activity (1.69 ± 1.84 h vs. 2.56 ± 2.20 h, P = 0.006), and HeartLogic index (11.07 ± 12.14 vs. 5.31 ± 5.13, P = 0.001). Sensor parameters measured worsening status leading up to HF events with recovery of values following treatment., Conclusions: Device-based physiologic sensors not only revealed progressive worsening leading up to HF events but also differentiated patients at increased risk of HF events when presumed to be clinically stable., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Recently published studies suggested that digoxin may increase mortality in heart failure with reduced ejection fraction (HFrEF). However, in the vast majority of former trials serum digoxin concentration (SDC) was not measured and therapy was not SDC-guided., Aim: To assess the impact of SDC-guided digoxin therapy on mortality in HFrEF patients., Methods: Data of 580 HFrEF patients were retrospectively analyzed. In patients on digoxin, SDC was measured every 3 months and digoxin dosage was SDC-guided (target SDC: 0.5-0.9 ng/mL). All-cause mortality of digoxin users and nonusers was compared after propensity score matching (PSM)., Results: After 7.1 ± 4.7 years follow-up period (FUP) all-cause mortality of digoxin users (n = 180) was significantly higher than nonusers (n = 297) (propensity-adjusted HR = 1.430; 95% CI = 1.134-1.804; P = .003). Patients having SDC of 0.9 to 1.1 ng/mL (n = 60) or > 1.1 ng/mL (n = 44) at any time during the FUP had an increased risk of all-cause mortality (HR = 1.750; 95% CI = 1.257-2.436, P = .001 and HR = 1.687; 95% CI = 1.153-2.466, P = .007), while patients having a maximal SDC < 0.9 ng/mL (n = 76) had similar mortality risk (HR = 1.139; 95% CI = 0.827-1.570, P = .426), compared to digoxin nonusers., Conclusions: According to our propensity-matched analysis, SDC-guided digoxin therapy was associated with increased all-cause mortality in optimally treated HFrEF patients, especially with SDC ≥0.9 ng/mL. These results reinforce the expert opinion that digoxin in HFrEF can only be used among carefully selected patients with close SDC monitoring., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Introduction: The novel two-lead cardiac resynchronization therapy (CRT)-DX system utilizes a floating atrial dipole on the implantable cardioverter-defibrillator lead, and when implanted with a left ventricular (LV) lead, offers a two-lead CRT system with AV synchrony. This study compared complication rates and CRT response among subjects implanted with a two-lead CRT-DX system to those subjects implanted with a standard three-lead CRT-D system., Methods and Results: A total of 240 subjects from the Sentus QP-Extended CRT Evaluation with Quadripolar Left Ventricular Leads postapproval study were selected to identify 120 matched pairs based on similar demographic characteristics using a Greedy algorithm. The complication-free rate was evaluated as the primary endpoint. All-cause mortality, heart failure hospitalizations, device diagnostic data, New York Heart Association (NYHA) class improvement, and defibrillator therapy were evaluated from clinical data, in-office interrogations, and remote monitoring throughout the follow-up period. Complication-free survival favored the CRT-DX group with 92.5% without a major complication compared to 85.0% in the CRT-D cohort (P = .0495; 95% confidence interval: 0.1%-14.9%) over a mean follow-up of 1.3 and 1.4 years, respectively. Incidence of all-cause mortality, heart failure hospitalizations, NYHA changes at 6 months postimplant, and percent of LV pacing during CRT therapy were similar in both device cohorts. Inappropriate shocks were more frequent in the CRT-D cohort with 5.8% of subjects receiving an inappropriate shock vs 0.8% in the CRT-DX cohort., Conclusion: The results of this subanalysis demonstrate that the CRT-DX system can provide similar CRT responses and significantly fewer complications when compared to a similar cohort with a conventional three-lead CRT-D system., (© 2020 The Authors. Journal of Cardiovascular Electrophysiology Published by Wiley Periodicals LLC.)

Purpose: Pneumothorax (PTX) following cardiac implantable electronic device procedures is traditionally treated with chest tube drainage (CTD). We hypothesized that, in a subset of patients, the less invasive needle aspiration (NA) may also be effective. We compared the strategy of primary NA with that of primary CTD in a single-center observational study., Methods: Of the 970 procedures with subclavian venous access between January 2016 and June 2018, 23 patients had PTX requiring intervention. Beginning with March 2017, the traditional primary CTD (9 cases) has been replaced by the "NA first" strategy (14 patients). Outcome measures were procedural success rate and duration of hospitalization evaluated both as time to event (log-rank test) and as a discrete variable (Wilcoxon-Mann-Whitney test)., Results: Needle aspiration was successful in 8/14 (57.1%) of the cases (95% CI 28.9-82.3%), whereas PTX resolved in all patients after CTD was 9/9 (100%, 95% CI 66.4-100.0%, p = 0.0481). Regarding length of hospital stay, intention to treat time to event analysis showed no difference between the two approaches (p = 0.73). Also, the median difference was not statistically significant (- 2.0 days, p = 0.17). In contrast, per protocol evaluation revealed reduced risk of prolonged hospitalization for NA patients (p = 0.0025) with a median difference of - 4.0 days (p = 0.0012). Failure of NA did not result in a meaningful delay in discharge timing as median difference was 1.5 days (p = 0.28)., Conclusions: Our data suggest that in a number of patients iatrogenic PTX may be successfully treated with NA resulting in shorter hospitalization without the risk of meaningful discharge delay in unsuccessful cases.

Background: The Micra transcatheter pacing system (TPS) is a miniaturized, single-chamber pacemaker system. Study reported herein is an initial experience with implantation of the Micra TPS., Methods: The leadless pacemaker was implanted in 10 patients with standard indications for a permanent pacemaker implantation. All hospitalization costs were calculated for all patients., Results: The mean age of the patients was 75 ± 7.1 years, 6 were men and 4 were women. Four patients had permanent atrial fibrillation as the basal rhythm and 6 patients had sinus rhythm. All patients had at least one relative contraindication that precluded the use of a traditional pacing system. Mean intraoperative ventricular sensing amplitude was 10.6 ± 5.4 mV, impedance 843 ± 185 ohms, and pacing threshold at 0.24 ms was 0.56 ± 0.23 V. At discharge, those values were 13.9 ± 5.6 mV, 667 ± 119 ohms and 0.47 ± 0.17, respectively. The mean duration of implantation procedure was 82 min, while mean fluoroscopy time was 3.5 min. Two patients developed hematoma at the groin puncture site post-implantation. In 1 case there was a need for erythrocyte mass transfusion and surgical intervention. Mean total time of hospitalization was 26 days and time from procedure to discharge 12 days. Average cost of hospitalization per 1 patient was 11,260.15 EUR minimal cost was 9,052.68 EUR, while maximal cost was 16,533.18 EUR., Conclusions: Implantation of leadless pacemakers is feasible, safe and provides advantages over the conventional system. Hospitalization costs vary for individual patients in wide range.

Aims: Patient selection is a key component of securing optimal patient outcomes with leadless pacing. We sought to describe and compare patient characteristics and outcomes of Micra patients with and without a primary pacing indication associated with atrial fibrillation (AF) in the Micra IDE trial., Methods and Results: The primary outcome (risk of cardiac failure, pacemaker syndrome, or syncope related to the Micra system or procedure) was compared between successfully implanted patients from the Micra IDE trial with a primary pacing indication associated with AF or history of AF (AF group) and those without (non-AF group). Among 720 patients successfully implanted with Micra, 228 (31.7%) were in the non-AF group. Reasons for selecting VVI pacing in non-AF patients included an expectation for infrequent pacing (66.2%) and advanced age (27.2%). More patients in the non-AF group had a condition that precluded the use of a transvenous pacemaker (9.6% vs. 4.7%, P = 0.013). Atrial fibrillation patients programmed to VVI received significantly more ventricular pacing compared to non-AF patients (median 67.8% vs. 12.6%; P < 0.001). The overall occurrence of the composite outcome at 24 months was 1.8% with no difference between the AF and non-AF groups (hazard ratio 1.36, 95% confidence interval 0.45-4.2; P = 0.59)., Conclusion: Nearly one-third of patients selected to receive Micra VVI therapy were for indications not associated with AF. Non-AF VVI patients required less frequent pacing compared to patients with AF. Risks associated with VVI therapy were low and did not differ in those with and without AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objective: Patients with electrical injury are considered to be at high risk of cardiac arrhythmias. Due to the small number of studies, there is no widely accepted guideline regarding the risk assessment and management of arrhythmic complications after electrical accident (EA). Our retrospective observational study was designed to determine the prevalence of ECG abnormalities and cardiac arrhythmias after EA, to evaluate the predictive value of cardiac biomarkers for this condition and to assess in-hospital and 30-day mortality., Methods: Consecutive patients presenting after EA at the emergency department of our institution between 2011 and 2016 were involved in the current analysis. ECG abnormalities and arrhythmias were analyzed at admission and during ECG monitoring. Levels of cardiac troponin I, CK and CK-MB were also collected. In-hospital and 30-day mortality data were obtained from hospital records and from the national insurance database., Results: Of the 480 patients included, 184 (38.3%) had suffered a workplace accident. The majority of patients (96.2%) had incurred a low-voltage injury (< 1000 V). One hundred and four (21.7%) patients had a transthoracic electrical injury while 13 (2.7%) patients reported loss of consciousness. The most frequent ECG disorders at admission were sinus bradycardia (< 60 bpm, n = 50, 10.4%) and sinus tachycardia (> 100 bpm, n = 21, 4.4%). Other detected arrhythmias were as follows: newly diagnosed atrial fibrillation (n = 1); frequent multifocal atrial premature complexes (n = 1); sinus arrest with atrial escape rhythm (n = 2); ventricular fibrillation terminated out of hospital (n = 1); ventricular bigeminy (n = 1); and repetitive nonsustained ventricular tachycardia (n = 1). ECG monitoring was performed in 182 (37.9%) patients for 12.7 ± 7.1 h at the ED. Except for one case with regular supraventricular tachycardia terminated via vagal maneuver and one other case with paroxysmal atrial fibrillation, no clinically relevant arrhythmias were detected during the ECG monitoring. Cardiac troponin I was measured in 354 (73.8%) cases at 4.6 ± 4.3 h after the EA and was significantly elevated only in one resuscitated patient. CK elevation was frequent, but CK-MB was under 5% in all patients. Both in-hospital and 30-day mortality were 0%., Conclusions: Most of cardiac arrhythmias in patients presenting after EA can be diagnosed by an ECG on admission, thus routine ECG monitoring appears to be unnecessary. In our patient cohort cardiac troponin I and CK-MB were not useful in risk assessment after EA. Late-onset malignant arrhythmias were not observed.

Background: Remote monitoring is an established, guideline-recommended technology with unequivocal clinical benefits; however, its ability to improve survival is contradictory., Objective: The aim of our study was to investigate the effects of remote monitoring on mortality in an optimally treated heart failure patient population undergoing cardiac resynchronization defibrillator therapy (CRT-D) implantation in a large-volume tertiary referral center., Methods: The population of this single-center, retrospective, observational study included 231 consecutive patients receiving CRT-D devices in the Medical Centre of the Hungarian Defence Forces (Budapest, Hungary) from January 2011 to June 2016. Clinical outcomes were compared between patients on remote monitoring and conventional follow-up., Results: The mean follow-up time was 28.4 (SD 18.1) months. Patients on remote monitoring were more likely to have atrial fibrillation, received heart failure management at our dedicated heart failure outpatient clinic more often, and have a slightly lower functional capacity. Crude all-cause mortality of remote-monitored patients was significantly lower compared with patients followed conventionally (hazard ratio [HR] 0.368, 95% CI 0.186-0.727, P=.004). The survival benefit remained statistically significant after adjustment for important baseline parameters (adjusted HR 0.361, 95% CI 0.181-0.722, P=.004)., Conclusions: In this single-center, retrospective study of optimally treated heart failure patients undergoing CRT-D implantation, the use of remote monitoring systems was associated with a significantly better survival rate., (©Peter Bogyi, Mate Vamos, Zsolt Bari, Balazs Polgar, Balazs Muk, Noemi Nyolczas, Robert Gabor Kiss, Gabor Zoltan Duray. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 26.07.2019.)

Background: The use of quadripolar (QP) left ventricular leads for cardiac resynchronization therapy (CRT) is intended to improve outcomes compared with conventional bipolar leads (BP). Hence, the number of implanted quadripolar CRT systems is increasing despite limited long-term data., Purpose: The aim of this study is to evaluate clinical response and long-term outcomes of CRT recipients who were implanted with quadripolar versus bipolar left ventricular leads., Methods: Data from consecutive patients receiving a CRT defibrillator in one German and one Hungarian tertiary referral center were retrospectively collected. Long-term survival and response to CRT were analyzed., Results: A total of 536 patients with structural heart disease and a mean left ventricular ejection fraction (LVEF) of 25% received a CRT defibrillator (CRT-D) system for primary (79%) or secondary (21%) prevention of sudden death. Comorbidities did not differ significantly between patients receiving a QP (n = 123) or a BP lead (n = 413). Procedure (101 vs. 120 min) and fluoroscopy times (14 vs. 20 min) were shorter in patients implanted with QP compared with BP (both p < 0.001). At 6 months follow-up, QP patients were more likely to respond to CRT measured as improvement in the New York Heart Association (NYHA) functional class (77% vs. 63%; p < 0.001). Use of QP left ventricle/left ventricular (LV) leads was associated with greater reduction in QRS duration compared with patients implanted with BP LV leads (- 21 ± 30 vs. - 8 ± 35 ms, p = 0.004). Mortality was not significantly different between patients with QP and patients with BP LV leads at a mean follow-up of 39 ± 31 months., Conclusion: Implantation of quadripolar left ventricular leads was associated with better CRT response compared with bipolar left ventricular leads.

Objectives: This study sought to report periprocedural outcomes and intermediate-term follow-up of hemodialysis patients undergoing Micra implantation., Background: Leadless pacemakers may be preferred in patients with limited vascular access and high-infection risk, such as patients on hemodialysis., Methods: Patients on hemodialysis at the time of Micra implantation attempt (n = 201 of 2,819; 7%) from the Micra Transcatheter Pacing Study investigational device exemption trial, Micra Transcatheter Pacing System Continued Access Study Protocol, and Micra Transcatheter Pacing System Post-Approval Registry were included in the analysis. Baseline characteristics, periprocedural outcomes, and intermediate-term follow-up were summarized., Results: Patients on hemodialysis at the time of Micra implantation attempt were on average 70.5 ± 13.5 years of age and 59.2% were male. The dialysis patients commonly had hypertension (80%), diabetes (61%), coronary artery disease (39%), and congestive heart failure (27%), and 72% had a condition that the implanting physician felt precluded the use of a transvenous pacemaker. Micra was successfully implanted in 197 patients (98.0%). Reasons for unsuccessful implantation included inadequate thresholds (n = 2) and pericardial effusion (n = 2). The median implantation time was 27 min (interquartile range: 20 to 39 min). There were 3 procedure-related deaths: 1 due to metabolic acidosis following a prolonged procedure duration in a patient undergoing concomitant atrioventricular nodal ablation and 2 deaths occurred in patients who needed surgical repair after perforation. Average follow-up was 6.2 months (range 0 to 26.7 months). No patients had a device-related infection or required device removal because of bacteremia., Conclusions: Leadless pacemakers represent an effective pacing option in this challenging patient population on chronic hemodialysis. The risk of infection appears low with an acceptable safety profile. (Micra Transcatheter Pacing Study; NCT02004873; Micra Transcatheter Pacing System Continued Access Study Protocol; NCT02488681; Micra Transcatheter Pacing System Post-Approval Registry; NCT02536118)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: The Micra Transcatheter Pacing System provides a rate adaptive pacing using an individually programmable three-axis accelerometer. We evaluated the short- and mid-term performance of the Micra activity sensor by testing all three available activity vectors during the exercise tests., Methods and Results: Implantation and follow-up data were prospectively collected from the patients undergoing Micra implantation at our institution. Patients underwent a 5-minute exercise test for each vector at predischarge (initial testing) and at scheduled in-office visits (repeat testing). On the basis of measurements of activity counts during the test, vectors were categorized to be adequate (excellent or acceptable) or poor. A total of 278 tests with 818 vector measurements were analyzed in 51 patients during follow-up (median duration was 18 months). Initial testing revealed the adequate quality of the nominal Vector 1 in 74.5% of the patients. Upon repeated testing at subsequent in-office visits, Vectors 1 and 3 were comparable (adequate quality in 64.7% vs 68.6% of the patients; P = 0.65) but better compared with Vector 2 (51.0%; P = 0.10 vs Vector 1, P = 0.01 vs Vector 3). In a subgroup of 45 patients programmed to VVIR mode, Vector 1 was selected in 46.7% of the patients after the initial test (Vector 2, 8.9%; Vector 3, 44.4%). Vector change was performed in 10 patients (22.2%) following repeated tests within 3 months of postimplantation., Conclusion: The three-axis accelerometer-based rate adaptive pacing feature proved to be feasible after manual selection of an adequate activity vector. Vector testing in Micra patients with chronotropic incompetence appears to be beneficial compared with the use of nominal Vector 1., (© 2018 Wiley Periodicals, Inc.)

Background: Data on preferred ICD lead type and optimal RV lead position in patients undergoing CRT-D implantation are limited., Objectives: To compare dual- versus single-coil ICD leads and non-apical versus apical RV lead position and their impact on clinical parameters and survival in CRT-D recipients., Methods: A total of 563 consecutive patients with advanced heart failure and indication for CRT-D implantation were enrolled in two European tertiary centers. Endpoints were improvement in NYHA functional class, changes in echo- and electrocardiographic parameters, and all-cause and cardiovascular mortality., Results: In this retrospective analysis, a total of 313 (56%) dual- and 250 (44%) single-coil ICD leads were used. RV leads were placed non-apically in 262 (47%) and apically in 296 (53%) patients, respectively. Over a mean follow-up of 41 ± 34 months, all-cause mortality and cardiovascular mortality were similar for patients with dual- versus single-coil ICD lead (adjusted HR 0.81, 95% CI 0.58-1.12 and aHR 1.22, 95% CI 0.73-2.04) and non-apical versus apical RV lead position (aHR 0.98, 95% CI 0.71-1.36 and aHR 0.76, 95% CI 0.44-1.31). Non-apical RV lead position was associated with greater reduction in QRS duration after CRT implantation (- 14.4 ± 32.1 vs. - 4.3 ± 34.3 ms, p < 0.001)., Conclusions: We found no association between ICD lead type or RV lead position and outcomes in CRT-D recipients. Non-apical RV lead position was associated with larger reduction in QRS duration.

Background: Micra is a leadless pacemaker that is implanted in the right ventricle and provides rate response via a 3-axis accelerometer (ACC). Custom software was developed to detect atrial contraction using the ACC enabling atrioventricular (AV) synchronous pacing., Objective: The purpose of this study was to sense atrial contractions from the Micra ACC signal and provide AV synchronous pacing., Methods: The Micra Accelerometer Sensor Sub-Study (MASS) and MASS2 early feasibility studies showed intracardiac accelerations related to atrial contraction can be measured via ACC in the Micra leadless pacemaker. The Micra Atrial TRacking Using A Ventricular AccELerometer (MARVEL) study was a prospective multicenter study designed to characterize the closed-loop performance of an AV synchronous algorithm downloaded into previously implanted Micra devices. Atrioventricular synchrony (AVS) was measured during 30 minutes of rest and during VVI pacing. AVS was defined as a P wave visible on surface ECG followed by a ventricular event <300 ms., Results: A total of 64 patients completed the MARVEL study procedure at 12 centers in 9 countries. Patients were implanted with a Micra for a median of 6.0 months (range 0-41.4). High-degree AV block was present in 33 patients, whereas 31 had predominantly intrinsic conduction during the study. Average AVS during AV algorithm pacing was 87.0% (95% confidence interval 81.8%-90.9%), 80.0% in high-degree block patients and 94.4% in patients with intrinsic conduction. AVS was significantly greater (P <.001) during AV algorithm pacing compared to VVI in high-degree block patients, whereas AVS was maintained in patients with intrinsic conduction., Conclusion: Accelerometer-based atrial sensing is feasible and significantly improves AVS in patients with AV block and a single-chamber leadless pacemaker implanted in the right ventricle., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The reliability of intrathoracic impedance monitoring for prediction of heart failure (HF) by implantable cardiac devices is controversial. Despite using additional device-based parameters described in the PARTNERS HF study, such as new onset of arrhythmias, abnormal autonomics, low biventricular pacing rate or patient activity level, the predictive power of device diagnostic algorithm is still in doubt. The objective of this study was to compare the device diagnostic algorithm described in the PARTNERS HF study to a newly developed algorithm applying refined diagnostic criteria., Methods: Fourty two patients were prospectively enrolled who had been implanted with an intrathoracic impedance and remote monitoring capable implantable cardiac defibrillator with a cardiac resychroniza-tion therapy (CRT-D) device in this observational study. If a remote OptiVolTM alert occurred, patients were checked for presence of HF symptoms. A new algorithm was derived from the original PARTNERS HF criteria, considering more sensitive cut-offs and changes of patterns of the device-based parameters., Results: During an average follow-up of 38 months, 722 remote transmissions were received. From the total of 128 transmissions with OptiVol alerts, 32 (25%) corresponded to true HF events. Upon multivariate discriminant analysis, low patient activity, high nocturnal heart rate, and low CRT pacing (< 90%) proved to be independent predictors of true HF events (all p < 0.01). Incorporating these three refined criteria in a new algorithm, the diagnostic yield of OptiVol was improved by increasing specific-ity from 37.5% to 86.5%, positive predictive value from 34.1% to 69.8% and area under the curve from 0.787 to 0.922 (p < 0.01), without a relevant loss in sensitivity (96.9% vs. 93.8%)., Conclusions: A refined device diagnostic algorithm based on the parameters of low activity level, high nocturnal heart rate, and suboptimal biventricular pacing might improve the clinical reliability of OptiVol alerts.

Patients with conventional pacemakers or implanted defibrillators are often considered for cardiac resynchronization therapy (CRT). Our aim was to summarize the available evidences regarding the clinical benefits of upgrade procedures. A systematic literature search was performed from studies published between 2006 and 2017 in order to compare the outcome of CRT upgrade vs. de novo implantations. Outcome data on all-cause mortality, heart failure events, New York Heart Association (NYHA) Class, QRS narrowing and echocardiographic parameters were analysed. A total of 16 reports were analysed comprising 489,568 CRT recipients, of whom 468,205 patients underwent de novo and 21,363 upgrade procedures. All-cause mortality was similar after CRT upgrade compared to de novo implantations (RR 1.19, 95% CI 0.88-1.60, p = 0.27). The risk of heart failure was also similar in both groups (RR 0.96, 95% CI 0.70-1.32, p = 0.81). There was no significant difference in clinical response after CRT upgrade compared to de novo implantations in terms of improvement in left ventricular ejection fraction (ΔEF de novo - 6.85% vs. upgrade - 9.35%; p = 0.235), NYHA class (ΔNYHA de novo - 0.74 vs. upgrade - 0.70; p = 0.737) and QRS narrowing (ΔQRS de novo - 9.6 ms vs. upgrade - 29.5 ms; p = 0.485). Our systematic review and meta-analysis of currently available studies reports that CRT upgrade is associated with similar risk for all-cause mortality compared to de novo resynchronization therapy. Benefits on reverse remodelling and functional capacity improved similarly in both groups suggesting that CRT upgrade may be safely and effectively offered in routine practice., Clinical Trial Registration: Prospero Database-CRD42016043747.

Aims: There is lack of conclusive evidence from randomized clinical trials on the efficacy and safety of upgrade to cardiac resynchronization therapy (CRT) in patients with implanted pacemakers (PM) or defibrillators (ICD) with reduced left ventricular ejection fraction (LVEF) and chronic heart failure (HF). The BUDAPEST-CRT Upgrade Study was designed to compare the efficacy and safety of CRT upgrade from conventional PM or ICD therapy in patients with intermittent or permanent right ventricular (RV) septal/apical pacing, reduced LVEF, and symptomatic HF., Methods and Results: The BUDAPEST-CRT study is a prospective, randomized, multicentre, investigator-sponsored clinical trial. A total of 360 subjects will be enrolled with LVEF ≤ 35%, NYHA functional classes II-IVa, paced QRS ≥ 150 ms, and a RV pacing ≥ 20%. Patients will be followed for 12 months. Randomization is performed in a 3:2 ratio (CRT-D vs. ICD). The primary composite endpoint is all-cause mortality, a first HF event, or less than 15% reduction in left ventricular (LV) end-systolic volume at 12 months. Secondary endpoints are all-cause mortality, all-cause mortality or HF event, and LV volume reduction at 12 months. Tertiary endpoints include changes in quality of life, NYHA functional class, 6 min walk test, natriuretic peptides, and safety outcomes., Conclusion: The results of our prospective, randomized, multicentre clinical trial will provide important information on the role of cardiac resynchronization therapy with defibrillator (CRT-D) upgrade in patients with symptomatic HF, reduced LVEF, and wide-paced QRS with intermittent or permanent RV pacing., Clinical Trials.gov Identifier: NCT02270840., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Leadless pacemaker systems have been designed to avoid the need for a pocket and transvenous lead. However, delivery of this therapy requires a new catheter-based procedure. This study evaluates the role of operator experience and different training strategies on procedural outcomes., Methods: A total of 726 patients underwent implant attempt with the Micra transcatheter pacing system (TPS; Medtronic, Minneapolis, MN, USA) by 94 operators trained in a teaching laboratory using a simulator, cadaver, and large animal models (lab training) or locally at the hospital with simulator/demo model and proctorship (hospital training). Procedure success, procedure duration, fluoroscopy time, and safety outcomes were compared between training methods and experience (implant case number)., Results: The Micra TPS procedure was successful in 99.2% of attempts and did not differ between the 55 operators trained in the lab setting and the 39 operators trained locally at the hospital (P = 0.189). Implant case number was also not a determinant of procedural success (P = 0.456). Each operator performed between one and 55 procedures. Procedure time and fluoroscopy duration decreased by 2.0% (P = 0.002) and 3.2% (P < 0.001) compared to the previous case. Major complication rate and pericardial effusion rate were not associated with case number (P = 0.755 and P = 0.620, respectively). There were no differences in the safety outcomes by training method., Conclusions: Among a large group of operators, implantation success was high regardless of experience. While procedure duration and fluoroscopy times decreased with implant number, complications were low and not associated with case number. Procedure and safety outcomes were similar between distinct training methodologies., (© 2017 Wiley Periodicals, Inc.)

A patient with ischaemic cardiomyopathy received a secondary prevention VVI implantable cardioverter-defibrillator (ICD) after an episode of sustained ventricular tachycardia (VT). Because of recurrent VTs transmitted via CareLink, medical therapy was optimized and VT ablation was performed. Subsequently, a fast VT with a typical short-long-short initiation developed. In addition, there was an increasing need for ventricular pacing due to sinus bradycardia. This new type of VT could be successfully dealt with by upgrading to DDD ICD and activating the Ventricular Rate Stabilization algorithm.

Background: Early performance of the Micra transcatheter pacemaker from the global clinical trial reported a 99.2% implant success rate, low and stable pacing capture thresholds, and a low (4.0%) rate of major complications up to 6 months., Objective: The purpose of this report was to describe the prespecified long-term safety objective of Micra at 12 months and electrical performance through 24 months., Methods: The Micra Transcatheter Pacing Study was a prospective single-arm study designed to assess the safety and efficacy of the Micra VVIR leadless/intracardiac pacemaker. Enrolled patients met class I or II guideline recommendations for de novo ventricular pacing. The long-term safety objective was freedom from a system- or procedure-related major complication at 12 months. A predefined historical control group of 2667 patients with transvenous pacemakers was used to compare major complication rates., Results: The long-term safety objective was achieved with a freedom from major complication rate of 96.0% at 12 months (95% confidence interval 94.2%-97.2%; P < .0001 vs performance goal). The risk of major complications for patients with Micra (N = 726) was 48% lower than that for patients with transvenous systems through 12 months postimplant (hazard ratio 0.52; 95% confidence interval 0.35-0.77; P = .001). Across subgroups of age, sex, and comorbidities, Micra reduced the risk of major complications compared to transvenous systems. Electrical performance was excellent through 24 months, with a projected battery longevity of 12.1 years., Conclusion: Long-term performance of the Micra transcatheter pacemaker remains consistent with previously reported data. Few patients experienced major complications through 12 months of follow-up, and all patient subgroups benefited as compared to transvenous pacemaker historical control group., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Device repositioning during Micra leadless pacemaker implantation may be required to achieve optimal pacing thresholds., Objective: The purpose of this study was to describe the natural history of acute elevated Micra vs traditional transvenous lead thresholds., Methods: Micra study VVI patients with threshold data (at 0.24 ms) at implant (n = 711) were compared with Capture study patients with de novo transvenous leads at 0.4 ms (n = 538). In both cohorts, high thresholds were defined as >1.0 V and very high as >1.5 V. Change in pacing threshold (0-6 months) with high (1.0 to ≤1.5 V) or very high (>1.5 V) thresholds were compared using the Wilcoxon signed-rank test., Results: Of the 711 Micra patients, 83 (11.7%) had an implant threshold of >1.0 V at 0.24 ms. Of the 538 Capture patients, 50 (9.3%) had an implant threshold of >1.0 V at 0.40 ms. There were no significant differences in patient characteristics between those with and without an implant threshold of >1.0 V, with the exception of left ventricular ejection fraction in the Capture cohort (high vs low thresholds, 53% vs 58%; P = .011). Patients with an implant threshold of >1.0 V decreased significantly (P < .001) in both cohorts. Micra patients with high and very high thresholds decreased significantly (P < .01) by 1 month, with 87% and 85% having 6-month thresholds lower than the implant value. However, when the capture threshold at implant was >2 V, only 18.2% had a threshold of ≤1 V at 6 months and 45.5% had a capture threshold of >2 V., Conclusions: Pacing thresholds in most Micra patients with elevated thresholds decrease after implant. Micra device repositioning may not be necessary if the pacing threshold is ≤2 V., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Two leadless pacemaker (PM) systems were recently developed to avoid pocket- and lead-related complications. As leadless PMs are implanted with a large delivery catheter, cardiac perforation remains a major safety concern. We aimed to provide a literature review on incidence of cardiac perforation with conventional and with leadless PM systems., Methods and Results: A systematic review over the last 25 years for studies reporting data on PM lead perforation was performed. Findings were synthesized descriptively. Where control groups were available, data were meta-analyzed to identify important clinical risk factors. A total of 28 studies comprising 60,744 patients undergoing conventional PM implantation were analyzed. The incidence of lead perforation ranged from 0% to 6.37% (mean 0.82%, weighted mean 0.31%, median of 0.40%). There was no significant difference in perforation risk between atrial and ventricular electrodes (POR 0.72, 95% confidence interval [CI], 0.28-1.87, P = 0.50) and between MRI conditional and conventional leads (POR 5.93, 95% CI, 0.72-48.76, P = 0.10). The use of active fixation leads (POR 4.25, 95% CI, 1.00-17.95, P = 0.05) and utilization of DDD versus VVI PM systems (POR 3.50, 95% CI, 1.48-8.28, P < 0.01) were associated with higher rates of perforation. In the 2 leadless PM studies, the incidence of cardiac perforation was 1.52% for each., Conclusion: PM lead perforation rates vary in individual studies with an overall low incidence. Leadless PMs seem to be associated with a slightly higher perforation risk, most likely reflecting a learning curve effect of this novel technology., (© 2016 Wiley Periodicals, Inc.)

Background: The Micra transcatheter pacemaker was designed to have similar functionality to conventional transvenous VVIR pacing systems. It provides rate adaptive pacing using a programmable 3-axis accelerometer designed to detect patient activity in the presence of cardiac motion., Objective: The purpose of this study was to evaluate the system's performance during treadmill tests to maximum exertion in a subset of patients within the Micra Transcatheter Pacing Study., Methods: Patients underwent treadmill testing at 3 or 6 months postimplant with algorithm programming at physician discretion. Normalized sensor rate (SenR) relative to the programmed upper sensor rate was modeled as a function of normalized workload in metabolic equivalents (METS) relative to maximum METS achieved during the test. A normalized METS and SenR were determined at the end of each 1-minute treadmill stage. The proportionality of SenR to workload was evaluated by comparing the slope from this relationship to the prospectively defined tolerance margin (0.65-1.35)., Results: A total of 69 treadmill tests were attempted by 42 patients at 3 and 6 months postimplant. Thirty tests from 20 patients who completed ≥4 stages with an average slope of 0.86 (90% confidence interval 0.77-0.96) confirmed proportionality to workload. On an individual test basis, 25 of 30 point estimates (83.3%) had a normalized slope within the defined tolerance range (range 0.46-1.08)., Conclusion: Accelerometer-based rate adaptive pacing was proportional to workload, thus confirming rate adaptive pacing commensurate to workload is achievable with an entirely intracardiac pacing system., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Benefits of cardiac resynchronization therapy (CRT) on morbidity and mortality in selected patients are well known. Although the number of upgrade procedures from single- or dual-chamber devices to CRT is increasing, there are only sparse data on the outcomes of upgrade procedures compared with de novo CRT. This study aimed to evaluate clinical response and survival in patients receiving de novo versus upgrade CRT defibrillator therapy., Methods and Results: Prospectively collected outcome data were compared in patients undergoing de novo or upgrade CRT defibrillator implantation at 3 implant centers in Germany and Hungary. Clinical response was defined as an improvement by at least one New York Heart Association (NYHA) functional class. CRT implantation was performed in 552 consecutive patients of whom 375 underwent a de novo and 177 an upgrade procedure. Upgrade patients were more often implanted for secondary prevention, suffered more often from atrial fibrillation, chronic kidney disease, diabetes mellitus, and dyslipidemia, and had more often a non-LBBB (left bundle branch block) wide QRS complex, and lower left ventricular ejection fraction. Upgrade procedures were associated with a lower response rate compared to the de novo group (57% versus 69%, P univariate=0.008, P multivariate=0.021). During the follow-up of 37±28 months, survival was worse after upgrade compared with de novo CRT defibrillator implantations (hazard ratio, 1.65; 95% confidence interval, 1.22-2.24; P =0.001) even after careful adjustment for important baseline variables (adjusted hazard ratio, 1.68; 95% confidence interval, 1.20-2.34; P =0.002) and after propensity-score matching (propensity-adjusted hazard ratio, 1.79; 95% confidence interval, 1.08-2.95; P =0.023)., Conclusions: Both clinical response and long-term survival were less favorable in patients undergoing CRT upgrade compared to de novo implantations., (© 2017 American Heart Association, Inc.)

Two major studies have shown that leadless pacemakers are safe and effective for patients requiring right ventricular rate responsive pacing therapy. This positive result recently led to FDA approval of one of the available leadless pacing devices. While this new technology is promising, it requires a different skill set for safe implantation. In this article, we review in detail the different steps required for implantation of tine-based leadless pacemakers while providing tips and tricks to minimize complications., (© 2016 Wiley Periodicals, Inc.)

Background: A leadless intracardiac transcatheter pacing system has been designed to avoid the need for a pacemaker pocket and transvenous lead., Methods: In a prospective multicenter study without controls, a transcatheter pacemaker was implanted in patients who had guideline-based indications for ventricular pacing. The analysis of the primary end points began when 300 patients reached 6 months of follow-up. The primary safety end point was freedom from system-related or procedure-related major complications. The primary efficacy end point was the percentage of patients with low and stable pacing capture thresholds at 6 months (≤2.0 V at a pulse width of 0.24 msec and an increase of ≤1.5 V from the time of implantation). The safety and efficacy end points were evaluated against performance goals (based on historical data) of 83% and 80%, respectively. We also performed a post hoc analysis in which the rates of major complications were compared with those in a control cohort of 2667 patients with transvenous pacemakers from six previously published studies., Results: The device was successfully implanted in 719 of 725 patients (99.2%). The Kaplan-Meier estimate of the rate of the primary safety end point was 96.0% (95% confidence interval [CI], 93.9 to 97.3; P<0.001 for the comparison with the safety performance goal of 83%); there were 28 major complications in 25 of 725 patients, and no dislodgements. The rate of the primary efficacy end point was 98.3% (95% CI, 96.1 to 99.5; P<0.001 for the comparison with the efficacy performance goal of 80%) among 292 of 297 patients with paired 6-month data. Although there were 28 major complications in 25 patients, patients with transcatheter pacemakers had significantly fewer major complications than did the control patients (hazard ratio, 0.49; 95% CI, 0.33 to 0.75; P=0.001)., Conclusions: In this historical comparison study, the transcatheter pacemaker met the prespecified safety and efficacy goals; it had a safety profile similar to that of a transvenous system while providing low and stable pacing thresholds. (Funded by Medtronic; Micra Transcatheter Pacing Study ClinicalTrials.gov number, NCT02004873.).

Background: The Shockless IMPLant Evaluation trial randomized 2500 patients receiving a first implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy-defibrillator device to have either defibrillation testing (DT) or no DT. It demonstrated that DT did not improve shock efficacy or reduce mortality., Objective: This prospective substudy evaluated the effect of DT on postoperative troponin levels and their predictive value for total and arrhythmic mortality., Methods: Troponin levels were measured between 6 and 24 hours after ICD implantation in 2200 of 2500 patients., Results: A postoperative serum troponin level above the upper limit of normal (ULN) was more common in patients undergoing DT (n = 509 [46.4%]) than in those not subjected to DT (n = 456 [41.3%]; P = .02). After excluding patients with known preoperative troponin levels above the ULN, consistent findings were observed (42.1% vs 37.5%; P = .04). During a mean follow-up of 3.1 ± 1.0 years, the annual mortality rate was increased in patients with postoperative troponin levels above the ULN (adjusted hazard ratio [HR] 1.43; 95% confidence interval [CI] 1.15-1.76; P = .001) irrespective of DT or no DT. Likewise, patients with elevated troponin levels had a significantly higher risk of arrhythmic death (adjusted HR 1.80; 95% CI 1.23-2.63; P = .002). The rate of first appropriate ICD shock (adjusted HR 0.89; 95% CI 0.71-1.12; P = .32) or failed appropriate shock (adjusted HR 1.02; 95% CI 0.59-1.76; P = .95) was similar in patients with or without troponin elevation., Conclusion: DT at the time of ICD implantation is associated with increased troponin levels, indicating subclinical myocardial injury caused by the procedure. Elevated troponin levels but not DT seem to predict clinical outcomes in ICD recipients., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Permanent cardiac pacing is the only effective treatment for symptomatic bradycardia, but complications associated with conventional transvenous pacing systems are commonly related to the pacing lead and pocket. We describe the early performance of a novel self-contained miniaturized pacemaker., Methods and Results: Patients having Class I or II indication for VVI pacing underwent implantation of a Micra transcatheter pacing system, from the femoral vein and fixated in the right ventricle using four protractible nitinol tines. Prespecified objectives were >85% freedom from unanticipated serious adverse device events (safety) and <2 V 3-month mean pacing capture threshold at 0.24 ms pulse width (efficacy). Patients were implanted (n = 140) from 23 centres in 11 countries (61% male, age 77.0 ± 10.2 years) for atrioventricular block (66%) or sinus node dysfunction (29%) indications. During mean follow-up of 1.9 ± 1.8 months, the safety endpoint was met with no unanticipated serious adverse device events. Thirty adverse events related to the system or procedure occurred, mostly due to transient dysrhythmias or femoral access complications. One pericardial effusion without tamponade occurred after 18 device deployments. In 60 patients followed to 3 months, mean pacing threshold was 0.51 ± 0.22 V, and no threshold was ≥2 V, meeting the efficacy endpoint (P < 0.001). Average R-wave was 16.1 ± 5.2 mV and impedance was 650.7 ± 130 ohms., Conclusion: Early assessment shows the transcatheter pacemaker can safely and effectively be applied. Long-term safety and benefit of the pacemaker will further be evaluated in the trial., Clinical Trial Registration: ClinicalTrials.gov ID NCT02004873., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Recent advances in miniaturization technologies and battery chemistries have made it possible to develop a pacemaker small enough to implant within the heart while still aiming to provide similar battery longevity to conventional pacemakers. The Micra Transcatheter Pacing System is a miniaturized single-chamber pacemaker system that is delivered via catheter through the femoral vein. The pacemaker is implanted directly inside the right ventricle of the heart, eliminating the need for a device pocket and insertion of a pacing lead, thereby potentially avoiding some of the complications associated with traditional pacing systems., Methods and Results: The Micra Transcatheter Pacing Study is currently undergoing evaluation in a prospective, multi-site, single-arm study. Approximately 720 patients will be implanted at up to 70 centres around the world. The study is designed to have a continuously growing body of evidence and data analyses are planned at various time points. The primary safety and efficacy objectives at 6-month post-implant are to demonstrate that (i) the percentage of Micra patients free from major complications related to the Micra system or implant procedure is significantly higher than 83% and (ii) the percentage of Micra patients with both low and stable thresholds is significantly higher than 80%. The safety performance benchmark is based on a reference dataset of 977 subjects from 6 recent pacemaker studies., Conclusions: The Micra Transcatheter Pacing Study will assess the safety and efficacy of a miniaturized, totally endocardial pacemaker in patients with an indication for implantation of a single-chamber ventricular pacemaker., Clinicaltrialsgov Registration Id: NCT02004873., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Long-term lead failure is a known complication of ICD therapy. The precise incidence and sequelae of insulation defects at the tricuspid level, however, are not well characterized., Objective: This study determined the risk of lead failure, with particular emphasis on insulation defects at the level of the tricuspid valve, in a large series of consecutive ICD recipients., Methods: Data from 357 consecutive patients, who had received transvenous 7 and 8 French ICD-leads (St. Jude Medical, Riata family) and were followed at our center, formed the basis of this study., Results: During a mean follow-up of 42 ± 24 months, 30 of 357 (8%) patients required surgical intervention due to lead failure. For overall lead defects, lead access via the subclavian vein and subpectoral device placement were independent predictors of overall lead failure (OR 3.47, 95% CI 1.38-8.72, P = 0.013 and OR 3.83, 95% CI 1.77-8.27, P = 0.001, respectively). Lead insulation defects at the level of the tricuspid valve accounted for 20% of all lead failures. Diagnosis of this specific insulation defect could only be established by fluoroscopy, while electrical parameters were within normal limits in all of these patients. On univariate but not on multivariate analysis the presence of nonischemic cardiomyopathy was a predictor of this lead complication (OR 8.2, CI 1.5-46.1, P = 0.02)., Conclusion: Insulation defects of 7 and 8 French ICD leads at the tricuspid level represent an important complication of device therapy. Even moderate changes in lead impedance within the normal limits at follow-up should prompt careful fluoroscopic evaluation to avoid spurious shocks., (© 2011 Wiley Periodicals, Inc.)

Introduction: Dronedarone has been shown to reduce cardiovascular hospitalizations or death in patients with atrial fibrillation (AF) and additional risk factors. This post hoc exploratory analysis examines its effects in the subgroup of lone AF patients., Methods and Results: Individual data from patients with lone AF enrolled in the EURIDIS, ADONIS, and ATHENA trials were entered in a central database. The effects of dronedarone compared to placebo on the composite endpoint of cardiovascular hospitalizations or death, and their individual components, were evaluated. A total of 432 (192 placebo and 240 dronedarone) patients (7% of the total population) were classified as having lone AF (69.4% male patients, mean age 64 ± 13 years). The patients were followed for 13.8 ± 7.2 months. The risk for first cardiovascular hospitalizations or death from any cause in the placebo group after 1 year was 25% in the lone AF group compared to 29% the rest of the population. For patients with lone AF, dronedarone led to a 44% reduction of cardiovascular hospitalizations or death (hazard ratio (HR) 0.56; 95%CI 0.36-0.88, P = 0.004) and to a 46% reduction in cardiovascular hospitalizations alone (HR 0.54; 95%CI 0.34-0.87, P = 0.004) compared to placebo. HR for all-cause mortality was 1.02 (95%CI 0.31-3.34, P = 0.885). All findings were homogeneous across the 3 studies and similar to those observed in the overall population., Conclusion: According to this post hoc analysis, patients with lone AF have a high risk for cardiovascular hospitalization within 1 year. Dronedarone when added to standard of care reduces the risk of cardiovascular hospitalizations in this population., (© 2011 Wiley Periodicals, Inc.)

Aims: There are continued debates on potential proarrhythmic effects of intracoronary bone marrow-derived progenitor cell (BMC) therapy for treatment of chronic heart failure. Implantable cardioverter-defibrillators (ICDs), a mainstay of heart failure therapy, provide the possibility of validly assessing arrhythmias in patients with chronic heart failure. The aim of this analysis was to assess the arrhythmogenic potential of intracoronary BMC therapy, continuously documented by ICD-stored intracardiac electrograms., Methods and Results: Matched cohort study of 112 patients receiving intracoronary administration of autologous BMC and 224 heart failure patients, matched for age, gender, and left ventricular ejection fraction fitted with an ICD. Within a follow-up period of 2 years (total patient-years at risk: 595 years), no significant difference was detected for ICD-stored episodes of ventricular tachycardia (VT; 25.0 vs. 27.1%; P = 0.779), VT/ventricular fibrillation treated by antitachycardia pacing or ICD shock (15.6 vs. 15.5%; P = 0.956), or death from arrhythmic cause (4.2 vs. 1.0%; P = 0.667). Predictors of occurrence of major arrhythmic events were parameters of advanced heart failure and implantation of ICD for secondary prevention; no influence could be detected for BMC administration (odds ratio = 1.198; P = 0.440)., Conclusion: There is no evidence that intracoronary administration of BMC aggravates life-threatening arrhythmias in patients with chronic heart failure.