Publications by authors named "Paul Knops"

Proof-of-concept to determine the direct biomechanical effects of cardiac contractility modulation (CCM) on living myocardial slices (LMS) from patients with end-stage heart failure (HF). Left ventricular LMS from patients with end-stage HF were produced and cultured in a biomimetic system with mechanical loading and electrical stimulation. CCM stimulation (80 mA, 40 ms delay, 21 ms duration) enhanced maximum contractile force (CCM: 1229 µN (587-2658) vs.

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Background: Areas of conduction disorders play an important role in both initiation and perpetuation of AF and can be recognized by specific changes in unipolar potential morphology. For example, EGM fractionation may be caused by asynchronous activation of adjacent cardiomyocytes because of structural barriers such as fibrotic strands. However, it is unknown whether there are sex differences in unipolar potential morphology.

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Article Synopsis
  • Normothermic heart perfusion (ESHP) allows for evaluating hearts from donors who experienced circulatory death, highlighting the need for sensitive metrics to gauge heart function before transplantation.* -
  • This study introduces electrophysiological (EP) parameters as potential biomarkers for assessing post-ischemic heart performance, using porcine hearts categorized by different warm ischemia durations for analysis.* -
  • Findings indicate that hearts affected by prolonged warm ischemia exhibit lower voltage and flatter potential slopes in electrical measurements, which correlate with their contractile performance and could assist in determining the viability of DCD hearts for transplantation.*
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The electrical arrhythmogenic substrate underlying the most common cardiac arrhythmia atrial fibrillation (AF) may consist of conduction disorders, low-voltage areas, or fractionated potentials. High-density and resolution epicardial mapping (HDREM) approaches have been introduced to quantify and visualize electrophysiological properties of the atria. These approaches are essential for obtaining innovative insights into arrhythmogenic substrates and identifying novel targets for therapy.

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Background: Ablation strategies targeting fractionated or low-voltage potentials have been widely used in patients with persistent types of atrial fibrillation (AF). However, recent studies have questioned their role in effectively representing sites of conduction slowing, and thus arrhythmogenic substrates.

Objectives: The authors studied the relationship between local conduction velocity (CV) and the occurrence of fractionated and/or low-voltage potentials in order to identify areas with critically slowing of conduction.

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Objective: The severity of atrial fibrillation (AF) can be assessed from intra-operative epicardial measurements (high-resolution electrograms), using metrics such as conduction block (CB) and continuous conduction delay and block (cCDCB). These features capture differences in conduction velocity and wavefront propagation, but ignore complementary properties such as the morphology of the action potentials. In this work, we focus on such complementary properties, and derive features to detect variations in the atrial potential waveforms.

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Background: Quantified features of local conduction heterogeneity due to pathological alterations of myocardial tissue could serve as a marker for the degree of electrical remodeling and hence be used to determine the stage of atrial fibrillation (AF).

Objectives: In this study, the authors investigated whether local directional heterogeneity (LDH) and anisotropy ratio, derived from estimated local conduction velocities (CVs) during AF, are suitable electrical parameters to stage AF.

Methods: Epicardial mapping (244-electrode array, interelectrode distance 2.

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(1) Background: Structural remodeling plays an important role in the pathophysiology of atrial fibrillation (AF). It is likely that structural remodeling occurs transmurally, giving rise to electrical endo-epicardial asynchrony (EEA). Recent studies have suggested that areas of EEA may be suitable targets for ablation therapy of AF.

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Background: Atrial fibrillation (AF) in patients with hypertrophic obstructive cardiomyopathy (HOCM) may be caused by a primary atrial myopathy. Whether HOCM-related atrial myopathy affects mainly electrophysiological properties of the left atrium (LA) or also the right atrium (RA) has never been investigated.

Objective: The purpose of this study was to characterize atrial conduction and explore differences in the prevalence of conduction disorders, potential fractionation, and low-voltage areas (LVAs) between the RA and LA during sinus rhythm (SR) as indicators of potential arrhythmogenic areas.

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Background: There is increasing awareness of sex-specific differences in epidemiology and pathophysiology of atrial fibrillation (AF). It is, however, unknown whether males and females differ in atrial electrophysiological properties during sinus rhythm (SR). The aim of this study was therefore to investigate sex-based (regional) differences in electrophysiological properties during SR of the right (RA) and left (LA) atrium including Bachmanns Bundle (BB) and pulmonary vein region (PVA).

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Aims: Areas of conduction inhomogeneity (CI) during sinus rhythm may facilitate the initiation and perpetuation of atrial fibrillation (AF). Currently, no tool is available to quantify the severity of CI. Our aim is to develop and validate a novel tool using unipolar electrograms (EGMs) only to quantify the severity of CI in the atria.

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Objective: Patients with persistent atrial fibrillation (AF) have more electrical endo-epicardial asynchrony (EEA) during sinus rhythm (SR) than patients without AF. Prior mapping studies indicated that particularly unipolar, endo- and/or epicardial electrogram (EGM) morphology may be indicators of EEA. This study aim to develop a novel method for estimating the degree of EEA by using unipolar EGM characteristics recorded from either the endo- and/or epicardium.

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Background: Low-level vagus nerve stimulation through the tragus (tLLVNS) is increasingly acknowledged as a therapeutic strategy to prevent and treat atrial fibrillation. However, a lack in understanding of the exact antiarrhythmic properties of tLLVNS has hampered clinical implementation.

Objectives: In this study, the authors aimed to study the effects of tLLVNS on atrial electrophysiology by performing intraoperative epicardial mapping during acute and chronic tLLVNS.

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Background And Aims: Atrial extrasystoles (AES) provoke conduction disorders and may trigger episodes of atrial fibrillation (AF). However, the direction- and rate-dependency of electrophysiological tissue properties on epicardial unipolar electrogram (EGM) morphology is unknown. Therefore, this study examined the impact of spontaneous AES on potential amplitude, -fractionation, -duration, and low-voltage areas (LVAs), and correlated these differences with various degrees of prematurity and aberrancy.

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Aims: Conventional right atrial appendage (RAA) pacing is associated with increased atrial activation time resulting in higher incidences of atrial tachyarrhythmia. Optimal pacing sites ideally shorten inter-atrial conduction delay, thereby decreasing atrial excitation time. We therefore examined the impact of programmed electrical stimulation (PES) from the right atrium (RA) and left atrium (LA) on the electrophysiological properties of Bachmann's bundle (BB).

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Background: Impairment of conduction across Bachmann's Bundle (BB) may cause advanced interatrial block (a-IAB), which in turn is associated with development of atrial fibrillation. However, the exact relation between a complete transverse line of conduction block (CB) across BB and the presence of a-IAB has not been studied.

Objective: The aims of this study are to determine whether (1) a complete transversal line of CB across BB established by high resolution mapping correlates with a-IAB on the surface ECG, (2) conduction abnormalities at the right and left atria correlate with a-IAB, and (3) excitation patterns are associated with ECG characteristics of a-IAB.

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Low-voltage areas (LVA) can be located exclusively at either the endocardium or epicardium. This has only been demonstrated for bipolar voltages, but the value of unipolar and omnipolar voltages recorded from either the endocardium and epicardium in predicting LVAs at the opposite layer remains unknown. The goal of this study was therefore to compare simultaneously recorded endo-epicardial unipolar and omnipolar potentials and to determine whether their voltage characteristics are predictive for opposite LVAs.

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Background: The presence of atrial fibrillation (AF) in heart failure (HF) patients with reduced ejection fraction is common and associated with an increased risk of stroke, hospitalization and mortality. Recent research findings indicate that a reduction in nicotinamide adenine dinucleotide (NAD) levels results in mitochondrial dysfunction, DNA damage and consequently cardiomyocyte impairment in experimental and clinical HF and AF. The HF-AF ENERGY trial aims to investigate the cardioprotective effects of the NAD precursor nicotinamide riboside (NR) treatment in ischemic heart disease patients diagnosed with AF.

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Background: Obesity predisposes to the development of atrial fibrillation (AF); however, the pathophysiology underlying this relation is only partly understood.

Objective: As low-voltage areas are considered indicators of the arrhythmogenic substrates promoting AF, our study aimed to compare the extensiveness of atrial low-voltage areas between obese and nonobese patients by using high-resolution epicardial mapping in order to identify predilection sites of low-voltage areas.

Methods: A total of 430 patients (131 (30%) obese and 299 (70%) nonobese) were matched resulting in 212 patients (body mass index [BMI] ≥30 kg/m: n = 106; BMI <30 kg/m: n = 106) undergoing cardiac surgery (mean age 63 ± 11 years; 161 male).

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Endo-epicardial asynchrony (EEA) is a new mechanism possibly maintaining atrial fibrillation. We aimed to determine the sensitivity and best recording modus to detect EEA on electrograms recorded from one atrial side using electrogram fractionation. Simultaneously obtained right atrial endo- and epicardial electrograms from 22 patients demonstrating EEA were selected.

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Background The significance of endo-epicardial asynchrony (EEA) and atrial conduction block (CB), which play an important role in the pathophysiology of atrial fibrillation (AF) during sinus rhythm is poorly understood. The aim of our study was therefore to examine 3-dimensional activation of the human right atrium (RA). Methods and Results Eighty patients (79% men, 39% history of AF) underwent simultaneous endo-epicardial sinus rhythm mapping of the inferior, middle and superior RA.

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Valvular heart disease (VHD) is a common risk factor for atrial fibrillation (AF). Conduction abnormalities (CA) during sinus rhythm (SR) across Bachmann's bundle (BB) are associated with AF development. The study goal is to compare electrophysiological characteristics across BB during SR between patients with ischemic (IHD) and/or VHD either with or without ischemic heart disease ((I)VHD), with/without AF history using high-resolution intraoperative epicardial mapping.

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Objectives: This study sought to quantify characteristics of atrial conduction disorders in patients with right atrial (RA) volume overload.

Background: Patients with an interatrial shunt are prone to developing atrial fibrillation (AF), which may be related to conduction disorders occurring due to atrial stretch.

Methods: Thirty-one patients undergoing surgery for an interatrial shunt (49 ± 14 years of age) underwent epicardial sinus rhythm mapping of the RA, Bachmann's bundle (BB), and left atrium (LA).

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Asynchronous activation of the endo-epicardium plays an important role in persistence of atrial fibrillation. So far, endo-epicardial asynchrony has only been demonstrated in the human right atrium. Our data provides the first evidence for existence of a considerable degree of endo-epicardial asynchrony in the human left atrium.

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Using unipolar atrial electrogram morphology as guidance for ablative therapy is regaining interest. Although standardly used in clinical practice during ablative therapy, the impact of filter settings on morphology of unipolar AF potentials is unknown. Thirty different filters were applied to 2,557,045 high-resolution epicardial AF potentials recorded from ten patients.

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