Electroanatomical mapping-guided left bundle branch area pacing in patients with structural heart disease and advanced conduction abnormalities.

AIMS: Left bundle branch area pacing (LBBAP) can be technically challenging and fluoroscopy-intense. Three-dimensional electroanatomical mapping (EAM) facilitates non-fluoroscopic lead navigation and electrogram mapping. We sought to prospectively evaluate the feasibility, safety, and outcomes of routine EAM-guided LBBAP in patients with structural heart disease (SHD) and advanced conduction abnormalities. METHODS AND RESULTS: Consecutive patients with SHD and conduction abnormalities who underwent an attempt at EAM-guided LBBAP were included. The feasibility, safety, procedural, and mid-term outcomes were evaluated. Electrical, echocardiographic, and clinical parameters were assessed at implantation and last follow-up. Thirty-two patients (68 ± 18 years; 19% female) were included, of which 75% had intrinsic QRS > 150 ms, 53% left bundle branch block, and 25% right bundle branch block. Primary EAM-guided LBBAP was successful in 29 patients (91%). The procedural duration was 95 (70-110) min, total fluoroscopy time 0.93 (0.40-1.73) min, and total fluoroscopy dose 35.4 (20.5-77.2) cGy cm2. Paced QRS duration (QRSd) was significantly shorter than intrinsic QRSd (121.9 ± 10.7 vs. 159.2 ± 34.4 ms; P < 0.001) and remained stable during the mean follow-up of 7.0 ± 5.9 months. The LBBAP capture threshold was 0.57 ± 0.23 V/0.4 ms at implantation and remained low during follow-up (0.58 ± 0.18 V/0.5 ± 0.2 ms; P = 0.877). Overall left ventricular ejection fraction improved significantly from 44.2 ± 14.3% at baseline to 49.4 ± 13.1% at follow-up (P = 0.009), New York Heart Association class from 2.4 ± 0.6 to 1.8 ± 0.6 (P = 0.002), respectively. No complications occurred that required intervention. CONCLUSION: Routine near-zero fluoroscopy EAM-guided LBBAP can safely be performed in patients with SHD and advanced conduction abnormalities with high success rates and favourable mid-term outcomes. Further studies are needed to investigate whether the use of EAM improves the overall outcome of conduction system pacing and to identify specific patient populations who benefit the most from EAM-guided lead implantation.

Major incidental findings on routine cardiovascular magnetic resonance imaging prior to first-time catheter ablation of atrial fibrillation.

INTRODUCTION: Preprocedural cardiovascular magnetic resonance (CMR) or computed tomography (CT) imaging of the left atrium/pulmonary veins is usually employed to guide catheter ablation of atrial fibrillation (AFCA). Incidental findings (IFs) are common on cardiac imaging prior to AFCA. However, previous studies have mainly focused on extracardiac IFs detected on CT scan. We aimed to assess the prevalence of relevant cardiac and extracardiac IFs on routine preprocedural CMR in a large patient cohort scheduled for first-time AFCA and report its impact on clinical decision-making and management. METHODS AND RESULTS: We included 2000 consecutive patients (62 ± 10 years; 59% male) who underwent CMR prior to first-time AFCA between April 2015 and March 2019. Among these patients 172 (8.6%) had a total of 184 major IFs. Detection of major IFs resulted in cancellation of the scheduled AFCA procedure in 88 patients (4.4%). Forty-two patients (2.1%) have never been ablated, 46 (2.3%) underwent postponed AFCA after a median time of 83 (32-213) days. The remaining 84 patients (4.2%) underwent an individualized approach to AFCA. The most common major IFs were accessory or anomalous PVs in 76 (3.8%), extracardiac abnormalities suspicious of malignancy in 29 (1.5%), and positive stress perfusion imaging in 19 (7.2% of 261 tested) patients. In 19 patients (1.0%) preprocedural CMR provided the diagnosis of a previously unknown structural cardiac disease. CONCLUSIONS: Unexpected relevant findings on routine preprocedural CMR affected clinical decision-making and management in 8.6% of patients scheduled for first-time AFCA. However, whether preprocedural CMR imaging may improve overall clinical outcome needs to be addressed in future research.

Three-Body Dynamics of the a_{1}(1260) Resonance from Lattice QCD.

Resonant hadronic systems often exhibit a complicated decay pattern in which three-body dynamics play a relevant or even dominant role. In this work we focus on the a_{1}(1260) resonance. For the first time, the pole position and branching ratios of a three-body resonance are calculated from lattice QCD using one-, two-, and three-meson interpolators and a three-body finite-volume formalism extended to spin and coupled channels. This marks a new milestone for ab initio studies of ordinary resonances along with hybrid and exotic hadrons involving three-body dynamics.

Increased Quality of Life Among Newly Diagnosed Patients With Heart Failure With Reduced Ejection Fraction in the Months After Initiation of Guideline-Directed Medical Therapy and Wearable Cardioverter Defibrillator Prescription.

BACKGROUND: The patient experience of heart failure involves a multi-impact symptom response with functional limitations, psychological changes, and significant treatment burden. OBJECTIVE: The aim of this study was to examine the change in patient-reported outcomes in newly diagnosed patients with heart failure and reduced ejection fraction (HFrEF) prescribed a wearable cardioverter defibrillator. METHODS: Adults hospitalized for new-onset heart failure, due to ischemic or nonischemic cardiomyopathy, and prescribed a wearable cardioverter defibrillator within 10 days post discharge were approached for inclusion. Participants completed the Kansas City Cardiomyopathy Questionnaire at 3 time points: baseline, day 90, and day 180. RESULTS: A total of 210 patients (26% female) were included. All Kansas City Cardiomyopathy Questionnaire subscales (physical limitation, symptom frequency, quality of life, and social limitation) showed improvement from baseline to day 90 (all Ps < .001). Only quality of life continued to improve from day 90 to day 180 (P < .001). By day 90, nearly 70% of patients showed an improvement in quality of life (67.9%, n = 91), and by day 180, more than 80% (82.8%, n = 111) reported a net improvement. Five patients (3.7%) reported a net decrease, and 18 patients (13.4%) had no net change in quality of life during the 180-day period. CONCLUSION: Patient-reported quality of life improved significantly among patients newly diagnosed with HFrEF and prescribed a wearable cardioverter defibrillator. These results suggest that pursuing guideline-directed medical therapy for HFrEF, while being protected by the wearable cardioverter defibrillator, is likely to provide symptom relief and improve quality of life.

Atrial fibrillation: is there a role for cardiac troponin?

Atrial fibrillation (AF) is the most common sustained arrhythmia, and its prevalence rate is expected to be doubled over the next decades. Despite the wide use of biomarkers in the management of different cardiac diseases such as myocardial infarction and heart failure, utilization of biomarkers in AF management is not routinely recommended by current guidelines. There is also growing evidence that higher levels of cardiac-specific troponin, as an intracellular protein involved in cardiomyocyte contraction, may be associated with the risk of incident and recurrent AF and its complications. In the present paper, we review the association between troponin and AF and propose clinical suggestions for use of troponin in the management of AF patients.

Impact of electroanatomical mapping-guided lead implantation on procedural outcome of His bundle pacing.

AIMS: Conventional His bundle pacing (HBP) can be technically challenging and fluoroscopy-intense, particularly in patients with His-Purkinje conduction disease (HPCD). Three-dimensional electroanatomical mapping (EAM) facilitates non-fluoroscopic lead navigation and HB electrogram mapping. We sought to assess the procedural outcome of routine EAM-guided HBP compared with conventional HBP in a real-world population and evaluate the feasibility and safety of EAM-guided HBP in patients with HPCD. METHODS AND RESULTS: We included 58 consecutive patients (72 ± 13 years; 71% male) who underwent an attempt to conventional (EAM- group; n = 29) or EAM-guided (EAM+ group; n = 29) HBP between June 2019 and April 2020. The centre's learning curve was initially determined (n = 40 cases) to define the conventional control group and minimize outcome bias favouring EAM-guided HBP. His bundle pacing was successful in 26 patients (90%) in the EAM+ and 27 patients (93%) in the EAM- group (P = 0.64). The procedure time was 90 (73-135) and 110 (70-130) min, respectively (P = 0.89). The total fluoroscopy time [0.7 (0.5-1.4) vs. 3.3 (1.4-6.5) min; P < 0.001] and fluoroscopy dose [21.9 (9.1-47.7) vs. 78.6 (27.2-144.9) cGycm2; P = 0.001] were significantly lower in the EAM+ than EAM- group. There were no significant differences between groups in His capture threshold (1.2 ± 0.6 vs. 1.4 ± 1.0 V/1.0 ms; P = 0.33) and paced QRS duration (113 ± 15 vs. 113 ± 17 ms; P = 0.89). In patients with HPCD, paced QRS duration was similar in both groups (121 ± 15 vs. 123 ± 12 ms; P = 0.77). The bundle branch-block recruitment threshold tended to be lower in the EAM+ than EAM- group (1.3 ± 0.7 vs. 1.8 ± 1.2 V/1.0 ms; P = 0.31). No immediate procedure-related complications occurred. One patient (2%) experienced lead dislodgement during 4-week follow-up. CONCLUSION: Implementation of routine EAM-guided HBP lead implantation is feasible and safe in a real-world cohort of patients with and without HPCD and results in a tremendous reduction in radiation exposure without prolonging procedure time or increasing procedure-related complications.

Transvenous revision of leads with cardiac perforation following device implantation-Safety, outcome, and complications.

INTRODUCTION: Cardiac perforation is a rare complication of cardiac implantable electronic device (CIED) implantation. Transvenous revision of perforated leads is associated with the risk of cardiac tamponade and death. Little is known about periprocedural complications and outcome of these patients. METHODS AND RESULTS: All patients referred to our department with evidence or suspicion of cardiac perforation following CIED implantation underwent chest X-ray, transthoracic echocardiography, device interrogation, and, if necessary, a cardiac computed tomography (CT)-scan to diagnose lead perforation and associated complications. Transvenous lead revision (TLR) was performed in all patients with evidence of lead perforation. Patient characteristics, procedural complications, and outcome were recorded and analyzed. Fifty-six patients (75 ± 10 years, 43% male) were diagnosed with cardiac perforation, 34 patients (61%) early within 30 days post-implantation, and 22 patients (39%) thereafter. The most frequent perforation site was the right ventricular (RV) apex (75%), followed by the RV free wall (16%) and the right atrial appendage (9%). A total of 16 patients (29%) presented with severe complications; 12 patients (21%) with pericardial effusion treated by pericardiocentesis before lead revision and four patients (7%) with hematothorax requiring drainage. Late perforations showed significantly more frequent cardiac tamponades (P = .041). TLR was performed without further complications in 54 patients (96%). None of the patients required surgical treatment or experienced in-hospital death. CONCLUSIONS: Cardiac perforation following CIED implantation is associated with severe complications in nearly one-third of the cases. Transvenous revision of the perforated lead can safely be performed with a very low complication rate.

Extraction of infected cardiac implantable electronic devices and the need for subsequent re-implantation.

BACKGROUND: Little is known about rates of re-implantation and outcomes of patients not implanted with a device after transvenous lead extraction (TLE) in cardiac device related infections (CDRI). METHODS: All patients with CDRI were included in a prospective registry. After TLE, the indication for re-implantation was evaluated according to the patients' history and most recent cardiac examinations. All patients were followed for complications and mortality. In addition, in patients discharged without device the frequency of device implantations was analyzed. RESULTS: Among 302 patients, only 123 (40.7%) met the indication for implantation of the same cardiac implantable electronic device (CIED), 68 (22.5%) received a different device and 111 (36.8%) patients were discharged without CIED. Reimplanted patients were younger (70 ±â€¯11 vs. 73 ±â€¯13 years; p = 0.004), more often male (83 vs. 69%, p = 0.006), had less systemic infection (38 vs. 60%; p < 0.001) and a higher prevalence of complete heart block (28 vs. 7%, p < 0.001). Reasons against re-implantation were: loss of indication (45%), never met indication (27%), patients' preference (17%), persistent infection (8%) and advanced age (3%). During 26 ±â€¯18 months of follow-up, mortality in both groups was similar after adjusting for cofactors (HR 0.79; 95% CI 0.49-1.29; p = 0.352). CONCLUSION: More than one third of patients undergoing TLE for CDRI in our study are not implanted with a new device. Careful evaluation of the initial CIED indication allows for detection of over treated patients and may avoid unnecessary device-related complications.

Effect of Exercise on Outcome after Ventricular Tachycardia Ablation in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.

Competitive sports and intensive exercise are associated with adverse outcomes in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). This study aimed to assess the role of exercise on long-term results of radiofrequency catheter ablation (RFCA) therapy of ventricular tachycardia (VT) in patients with ARVD/C. Exercise participation was evaluated by telephone or in-person interviews in patients from our ARVD/C registry with previous VT ablation (38 patients, 26 males, age 52.6±14.1years). Of 38 patients, 30 were involved in sports activities before RFCA. Only the minority of our patient population (21.1%) had a sedentary lifestyle before RFCA; 42.1 and 36.8% reported recreational or competitive sports, respectively. During the follow-up period of 52.5±31.4 months, 23 of the total 38 patients with previous RFCA (60.5%) remained free from VT recurrence. In univariate and binary logistic regression analysis, only advanced age was significantly associated with VT recurrence, with a hazard ratio of 1.15, and 95% confidence interval 1.05-1.26 (p=0.004). The results of our observational study indicate that recreational sports do not impair long-term results after RFCA treatment compared with a sedentary lifestyle. Furthermore, the dynamic component of recreational exercise did not affect the outcome of VT ablation in our patient population. Recreational exercise at low to moderate intensity is not associated with an increased risk for VT recurrence after catheter ablation in patients with ARVD/C.

Cardiovascular magnetic resonance imaging in patients with cardiac implantable electronic devices: best practice and real-world experience.

AIMS: Cardiovascular magnetic resonance (CMR) imaging has long been a contraindication for patients with a cardiac implantable electronic device (CIED). Recent studies support the feasibility and safety for non-thoracic magnetic resonance imaging, but data for CMR are sparse. The aim of the current study was to determine the safety in patients with magnetic resonance (MR)-conditional or non-MR-conditional CIED and to develop a best practice approach. METHODS AND RESULTS: All patients with a CIED undergoing CMR imaging (1.5 T) between April 2014 and April 2017 were included in the study. Devices were programmed according to the standardized protocol directly before and after the CMR examination. Follow-up interrogation was performed 6 months after CMR examination. Results were compared with a large, reference cohort of CIED patients not undergoing any MR examination. A total of 200 consecutive patients with a CIED (non-MR-conditional, n = 103) were included in the study. Directly after CMR imaging, one device failure (0.5%, battery status = end of service) was noted necessitating premature generator replacement. In three patients (2%) of pacemaker/implantable cardioverter-defibrillator (ICD) carriers a sustained ventricular tachycardia (VT) occurred during CMR imaging. Ten ICD showed a decrease in battery capacity immediately after CMR. Overall, the reference cohort showed comparable changes of CIED function during follow-up. CONCLUSION: With adherence to a standardized protocol and established exclusion criteria CMR imaging could safely be performed in patients with a CIED. The potential risks of device malfunction necessitate the presence of a device trained individual during the entire CMR examination. If there is a history of VT storm the attendance of an experienced cardiologist, should be mandatory.

Prevention of sudden cardiac death by the implantable cardioverter-defibrillator.

Sudden cardiac death (SCD) is a leading cause of death. The advent of the implantable cardioverter­defibrillator (ICD) has revolutionized prevention of SCD in high­risk patients with underlying cardiac diseases. However, several challenges remain. Identification of patients at risk who should receive an ICD is suboptimal, and the sole criterion applied in clinical practice is a severely reduced left ventricular ejection fraction despite the fact that SCD occurs mostly in patients with preserved or mildly reduced ejection fraction. Additionally, the majority of patients that do receive the ICD will not benefit from the device at the end. Therefore, improved risk stratification approaches to guide selection of patients for ICD implantation are definitely needed. There are several novel features and developments in the field with the subcutaneous defibrillator being probably the most important one and having the potential to substantially influence clinical practice. The role of catheter ablation of ventricular tachycardia, and particularly the potential to abolish the need for ICD implantation at least in selected patient groups, should be further defined. Internists and general practitioners play a significant role in the management of ICD patients, from identification of candidates for ICD implantation to early detection and appropriate treatment of complications.

[Telemonitoring of implanted cardiac devices : Clinical necessity or senseless luxury?] / Telemonitoring von implantierten kardialen Devices : Klinische Notwendigkeit oder sinnloser Luxus?

In addition to the telemedical follow-up at a fixed point in time, there is the possibility of a close-meshed telemetric monitoring in modern devices. By transferring device and patient-specific data, errors in the integrity of the device or electrodes and cardiac arrhythmias can be detected early, in various studies significantly reducing the number of outpatient or inpatient visits and the rate of inadequate implantable cardioverter-defibrillator (ICD) therapies. Measurement of various surrogate parameters allows better clinical assessment of heart failure patients, yet no improvement in outcome with therapy guided by telemetric data has been demonstrated. Retrospective analyzes, a prospective randomized study, and various meta-analyzes identified a reduction in all-cause mortality through the use of remote monitoring. This effect is mainly due to monitoring as closely as possible, timely examination of the findings, accordingly early interventions and specification of clear therapeutic regimens in certain clinical scenarios. Such comprehensive patient care requires the creation of telemonitoring centers with appropriate structural and personal equipment, whereby the creation of such structures has not yet been remunerated in the German healthcare system. In this paper, an overview of remote monitoring and identify possibilities and limitations of device-based telemedical monitoring is provided.

The Diagnosis and Treatment of Pacemaker-Associated Infection.

BACKGROUND: Approximately 105 000 cardiac electronic devices are newly implanted in Germany each year. Germany has the highest implantation rate with respect to population of any European country. Infections in cardiac implants are serious complications, with an associated in-hospital mortality of 5-15%. It is thus very important to optimize the diagnostic and therapeutic strategies by which such infections can be detected early and treated effectively. METHODS: This review is based on pertinent publications retrieved by a search in PubMed, with special attention to the current recommendations of international medical specialty societies. RESULTS: According to the international literature, the incidence of device-associated infection is 1.7% (in six months) for implanted defibrillators and 9.5% (in two years) for resynchronization devices. No absolute figures on infection rates are available for Germany. Infection can involve either the site where the impulse generator is implanted or the intravascular portion of the electrodes. The most important elements of the diagnostic evaluation are: assessment of the local findings; pathogen identification by culture of peripheral blood, swabs of the infected site, or material recovered at surgery; and transesophageal echocardiography to detect endocarditic deposits on the electrodes or cardiac valves. The treatment consists of appropriate antibiotic administration and the complete removal of all foreign material. These special extractions are generally performed via the transvenous route. With the aid of various sheath systems, the procedure can be carried out safely and effectively, with a success rate above 95% and a complication rate below 3%. The indications for the implantation of a new device after eradication of the infection should be critically reassessed. CONCLUSION: Untreated infection carries a high mortality. Evaluation and treatment according to a standardized clinical algorithm facilitate correct and timely diagnosis and the choice of an appropriate therapeutic strategy.

Cardiac resynchronization therapy in the ageing population - With or without an implantable defibrillator?

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective treatment option for systolic heart failure, but the benefit of an additional implantable cardioverter-defibrillator (ICD) in elderly patients is not well established. The aim of our study was to evaluate the impact of an additional ICD on survival in elderly CRT recipients. METHODS: Patients aged ≥75 years with an indication for CRT and primary preventive ICD therapy, which underwent implantation of either a CRT-pacemaker (CRT-P) or CRT-defibrillator (CRT-D) were included in the study. Patient characteristics, procedural and follow-up data, and subsequent all-cause mortality were analyzed. RESULTS: A total of 775 consecutive patients underwent CRT implantation, whereof 177 patients fulfilled the inclusion criteria. Of these, 80 patients with CRT-P and 97 with CRT-D formed the two study groups. Patients in the CRT-P group were significantly older (82.6 ±â€¯4.5 vs. 77.8 ±â€¯1.9 years, p < 0.001) and more often female (44 vs. 25%; p < 0.001), had a better left ventricular ejection fraction (29.5 ±â€¯5.7 vs. 27.4 ±â€¯6.0%; p = 0.019) and narrower QRS-complex (150 ±â€¯19 vs. 158 ±â€¯18 ms; p = 0.025). During a mean follow-up of 26 ±â€¯19 months, 62 (35%) study patients died, 28 (35%) in the CRT-P and 34 (35%) in the CRT-D group (p = 0.994). The Kaplan-Meier analysis of survival probability showed no significant difference between the two groups (p = 0.562). CONCLUSION: In our study, an additional ICD had no impact on survival in elderly patients undergoing implantation of a CRT device. Randomized controlled trials have to confirm this finding.

Molecular partners of hNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, suggest its involvement in distinct cellular processes relevant to congenital disorders of glycosylation, cancer, neurodegeneration and a variety of further pathologies.

This study provides first insights into the involvement of hNOT/ALG3, the human counterpart of the Drosophila Neighbour of TID and yeast ALG3 gene, in various putative molecular networks. HNOT/ALG3 encodes two translated transcripts encoding precursor proteins differing in their N-terminus and showing 33% identity with the yeast asparagine-linked glycosylation 3 (ALG3) protein. Experimental evidence for the functional homology of the proteins of fly and man in the N-glycosylation has still to be provided. In this study, using the yeast two-hybrid technique we identify 17 molecular partners of hNOT-1/ALG3-1. We disclose the building of hNOT/ALG3 homodimers and provide experimental evidence for its in vivo interaction with the functionally linked proteins OSBP, OSBPL9 and LRP1, the SYPL1 protein and the transcription factor CREB3. Regarding the latter, we show that the 55 kDa N-glycosylated hNOT-1/ALG3-1 molecule binds the N-glycosylated CREB3 precursor but does not interact with CREB3's proteolytic products specific to the endoplasmic reticulum and to the nucleus. The interaction between the two partners is a prerequisite for the proteolytic activation of CREB3. In case of the further binding partners, our data suggest that hNOT-1/ALG3-1 interacts with both OSBPs and with their direct targets LRP1 and VAMP/VAP-A. Moreover, our results show that various partners of hNOT-1/ALG3-1 interact with its diverse post translationally processed products destined to distinct cellular compartments. Generally, our data suggest the involvement of hNOT-1/ALG3-1 in various molecular contexts determining essential processes associated with distinct cellular machineries and related to various pathologies, such as cancer, viral infections, neuronal and immunological disorders and CDG.

Author Correction: Volcanic influence on centennial to millennial Holocene Greenland temperature change.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Characterizing left ventricular mechanical and electrical activation in patients with normal and impaired systolic function using a non-fluoroscopic cardiovascular navigation system.

PURPOSE: Cardiac disease frequently has a degenerative effect on cardiac pump function and regional myocardial contraction. Therefore, an accurate assessment of regional wall motion is a measure of the extent and severity of the disease. We sought to further validate an intra-operative, sensor-based technology for measuring wall motion and strain by characterizing left ventricular (LV) mechanical and electrical activation patterns in patients with normal (NSF) and impaired systolic function (ISF). METHODS: NSF (n = 10; ejection fraction = 62.9 ± 6.1%) and ISF (n = 18; ejection fraction = 35.1 ± 13.6%) patients underwent simultaneous electrical and motion mapping of the LV endocardium using electroanatomical mapping and navigational systems (EnSite™ NavX™ and MediGuide™, Abbott). Motion trajectories, strain profiles, and activation times were calculated over the six standard LV walls. RESULTS: NSF patients had significantly greater motion and systolic strains across all LV walls than ISF patients. LV walls with low-voltage areas showed less motion and systolic strain than walls with normal voltage. LV electrical dyssynchrony was significantly smaller in NSF and ISF patients with narrow-QRS complexes than ISF patients with wide-QRS complexes, but mechanical dyssynchrony was larger in all ISF patients than NSF patients. The latest mechanical activation was most often the lateral/posterior walls in NSF and wide-QRS ISF patients but varied in narrow-QRS ISF patients. CONCLUSIONS: This intra-operative technique can be used to characterize LV wall motion and strain in patients with impaired systolic function. This technique may be utilized clinically to provide individually tailored LV lead positioning at the region of latest mechanical activation for patients undergoing cardiac resynchronization therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01629160.