Advanced image-supported lead placement in cardiac resynchronisation therapy: protocol for the multicentre, randomised controlled ADVISE trial and early economic evaluation

INTRODUCTION: Achieving optimal placement of the left ventricular (LV) lead in cardiac resynchronisation therapy (CRT) is a prerequisite in order to achieve maximum clinical benefit, and is likely to help avoid non-response. Pacing outside scar tissue and targeting late activated segments may improve outcome. The present study will be the first randomised controlled trial to compare the efficacy of real-time image-guided LV lead delivery to conventional CRT implantation. In addition, to estimate the cost-effectiveness of targeted lead implantation, an early decision analytic model was developed, and described here. METHODS AND ANALYSIS: A multicentre, interventional, randomised, controlled trial will be conducted in a total of 130 patients with a class I or IIa indication for CRT implantation. Patients will be stratified to ischaemic heart failure aetiology and 1:1 randomised to either empirical lead placement or live image-guided lead placement. Ultimate lead location and echocardiographic assessment will be performed by core laboratories, blinded to treatment allocation and patient information. Late gadolinium enhancement cardiac magnetic resonance imaging (CMR) and CINE-CMR with feature-tracking postprocessing software will be used to semi-automatically determine myocardial scar and late mechanical activation. The subsequent treatment file with optimal LV-lead positions will be fused with the fluoroscopy, resulting in live target-visualisation during the procedure. The primary endpoint is the difference in percentage of successfully targeted LV-lead location. Secondary endpoints are relative percentage reduction in indexed LV end-systolic volume, a hierarchical clinical endpoint, and quality of life. The early analytic model was developed using a Markov-model, consisting of seven mutually exclusive health states. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Research Ethics Committee Utrecht (NL73416.041.20). All participants are required to provide written informed consent. Results will be submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05053568; Trial NL8666

On-Screen Image-Guided Lead Placement in Cardiac Resynchronization Therapy: Feasibility and Outcome in a Multicenter Setting

Background: Image guidance to assist left ventricular (LV) lead placement may improve outcome after cardiac resynchronization therapy (CRT), but previous approaches and results varied greatly, and multicenter feasibility is lacking altogether. Objective: We sought to investigate the multicenter feasibility of image guidance for periprocedural assistance of LV lead placement for CRT. Methods: In 30 patients from 3 hospitals, cardiac magnetic resonance imaging was performed within 3 months prior to CRT to identify myocardial scar and late mechanical activation (LMA). LMA was determined using radial strain, plotted over time. Segments without scar but clear LMA were classified as optimal for LV lead placement, according to an accurate 36-segment model of the whole heart. LV leads were navigated using image overlay with periprocedural fluoroscopy. After 6 months, volumetric response and super-response were defined as ≥15% or ≥30% reduction in LV end-systolic volume, respectively. Results: Periprocedural image guidance was successfully performed in all CRT patients (age 66 ± 10 years; 59% men, 62% with nonischemic cardiomyopathy, 69% with left bundle branch block). LV leads were placed as follows: within (14%), adjacent (62%), or remote (24%) from the predefined target. According to the conventional 18-segment model, a remote position occurred only once (3%). On average, 86% of patients demonstrated a volumetric response (mean LV end-systolic volume reduction 36 ± 29%), and 66% of all patients were super-responders. Conclusion: On-screen image guidance for LV lead placement in CRT was feasible in a multicenter setting. Efficacy will be further investigated in the randomized controlled ADVISE (Advanced Image Supported Lead Placement in Cardiac Resynchronization Therapy) trial (NCT05053568)

Targeted next-generation sequencing of the 16S-23S rRNA region for culture-independent bacterial identification - increased discrimination of closely related species

The aim of this study was to develop an easy-to-use culture-free diagnostic method based on next generation sequencing (NGS) of PCR amplification products encompassing whole 16S-23S rRNA region to improve the resolution of bacterial species identification. To determine the resolution of the new method 67 isolates were subjected to four identification methods: Sanger sequencing of the 16S rRNA gene; NGS of the 16S-23S rRNA region using MiSeq (Illumina) sequencer; Microflex MS (Bruker) and VITEK MS (bioMerieux). To evaluate the performance of this new method when applied directly on clinical samples, we conducted a proof of principle study with 60 urine samples from patients suspected of urinary tract infections (UTIs), 23 BacT/ALERT (bioMerieux) positive blood culture bottles and 21 clinical orthopedic samples. The resolution power of NGS of the 16S-23S rRNA region was superior to other tested identification methods. Furthermore, the new method correctly identified pathogens established as the cause of UTIs and blood stream infections with conventional culture. NGS of the 16S-23S rRNA region also showed increased detection of bacterial microorganisms in clinical samples from orthopedic patients. Therefore, we conclude that our method has the potential to increase diagnostic yield for detection of bacterial pathogenic species compared to current methods

The nature of the memory trace and its neurocomputational implications

The brain processes underlying cognitive tasks must be very robust. Disruptions such as the destruction of large numbers of neurons, or the impact of alcohol and lack of sleep do not have negative effects except when they occur in an extreme form. This robustness implies that the parameters determining the functioning of networks of individual neurons must have large ranges or there must exist stabilizing mechanisms that keep the functioning of a network within narrow bounds. The simulation of a minimal neuronal architecture necessary to study cognitive tasks is described, which consists of a loop of three cell-assemblies. A crucial factor in this architecture is the critical threshold of a cell-assembly. When activated at a level above the critical threshold, the activation in a cell-assembly is subject to autonomous growth, which leads to an oscillation in the loop. When activated below the critical threshold, excitation gradually extinguishes. In order to circumvent the large parameter space of spiking neurons, a rate-dependent model of neuronal firing was chosen. The resulting parameter space of 12 parameters was explored by means of a genetic algorithm. The ranges of the parameters for which the architecture produced the required oscillations and extinctions, turned out to be relatively narrow. These ranges remained narrow when a stabilizing mechanism, controlling the total amount of activation, was introduced. The architecture thus shows chaotic behaviour. Given the overall stability of the operation of the brain, it can be concluded that there must exist other mechanisms that make the network robust. Three candidate mechanisms are discussed: synaptic scaling, synaptic homeostasis, and the synchronization of neural spikes

Real-time correction of respiratory-induced cardiac motion during electroanatomical mapping procedures

Treatment planning during catheter interventions in the heart is often based on electromechanical tissue characteristics obtained by endocardial surface mapping (ESM). Since studies have shown respiratory-induced cardiac motion of over 5 mm in different directions, respiratory motion may cause ESMs artifacts due to faulty interpolation. Hence, we designed and tested a real-time respiration-correction algorithm for ESM. An experimental phantom was used to design the correction algorithm which was subsequently evaluated in five pigs. A piezo-respiratory belt transducer was used to measure the respiration. The respiratory signal was inserted to the NOGA®XP electromechanical mapping system via the ECG leads. The results of the correction were assessed by measuring the displacement of a reference point and the registration error of the ESM on a CMR scan before and after correction. In the phantom experiment, the reference point displacement was 6.5 mm before and 1.1 mm after correction and the registration errors were 2.8 ± 2.2 and 1.9 ± 1.3 mm, respectively. In the animals, the average reference point displacement (apex) was reduced from 2.6 ± 1.0 mm before to 1.2 ± 0.3 mm after correction (P <0.05). The in vivo registration error of the ESM and the CMR scan did not significantly improve. Even though the apical movement appreciated in pigs is small, the correction algorithm shows a decrease in displacement after correction. Application of this algorithm omits the use of the time-consuming respiratory gating during ESM and may lead to less respiratory artifacts in clinical endocardial mapping procedures

Real-time correction of respiratory-induced cardiac motion during electroanatomical mapping procedures

Treatment planning during catheter interventions in the heart is often based on electromechanical tissue characteristics obtained by endocardial surface mapping (ESM). Since studies have shown respiratory-induced cardiac motion of over 5 mm in different directions, respiratory motion may cause ESMs artifacts due to faulty interpolation. Hence, we designed and tested a real-time respiration-correction algorithm for ESM. An experimental phantom was used to design the correction algorithm which was subsequently evaluated in five pigs. A piezo-respiratory belt transducer was used to measure the respiration. The respiratory signal was inserted to the NOGA®XP electromechanical mapping system via the ECG leads. The results of the correction were assessed by measuring the displacement of a reference point and the registration error of the ESM on a CMR scan before and after correction. In the phantom experiment, the reference point displacement was 6.5 mm before and 1.1 mm after correction and the registration errors were 2.8 ± 2.2 and 1.9 ± 1.3 mm, respectively. In the animals, the average reference point displacement (apex) was reduced from 2.6 ± 1.0 mm before to 1.2 ± 0.3 mm after correction (P <0.05). The in vivo registration error of the ESM and the CMR scan did not significantly improve. Even though the apical movement appreciated in pigs is small, the correction algorithm shows a decrease in displacement after correction. Application of this algorithm omits the use of the time-consuming respiratory gating during ESM and may lead to less respiratory artifacts in clinical endocardial mapping procedures