Decrement Evoked Potential Mapping to Guide Ventricular Tachycardia Ablation: Elucidating the Functional Substrate.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadEmpirical approaches to targeting the ventricular tachycardia (VT) substrate include mapping of late potentials, local abnormal electrogram, pace-mapping and homogenisation of the abnormal signals. These approaches do not try to differentiate between the passive or active role of local signals as the critical components of the VT circuit. By not considering the functional components, these approaches often view the substrate as a fixed anatomical barrier. Strategies to improve the success of VT ablation need to include the identification of critical functional substrate. Decrement-evoked potential (DeEP) mapping has been developed to elucidate this using an extra-stimulus added to a pacing drive train. With knowledge translation in mind, the authors detail the evolution of the DeEP concept by way of a study of simultaneous panoramic endocardial mapping in VT ablation; an in silico modelling study to demonstrate the factors influencing DeEPs; a multicentre VT ablation validation study; a practical approach to DeEP mapping; the potential utility of DeEPs to identify arrhythmogenic atrial substrate; and, finally, other functional mapping strategies

Plasma B-type natriuretic peptide levels are poorly related to the occurrence of ischemia or ventricular arrhythmias during symptom-limited exercise in low-risk patients

The usefulness of B-type natriuretic peptide (BNP) as a marker of ischemia is controversial. BNP levels have predicted arrhythmias in various settings, but it is unknown whether they are related to exercise-induced ischemic ventricular arrhythmias. We analyzed in 63 patients (64 ±14 years, 65% male, 62% with known coronary disease) undergoing exercise stress single-photon emission computed tomography (SPECT) the association between plasma BNP values (before and 15 min after exercise) and the occurrence of ischemia or ventricular arrhythmias during the test. Exercise test (8.1 ±2.7 min, 7.4 ±8.1 metabolic equivalents, 82 ±12% of maximal predicted heart rate) induced reversible perfusion defects in 23 (36%) patients. Eight (13%) patients presented significant arrhythmias (≥ 7 ventricular premature complexes/min, couplets, or non-sustained ventricular tachycardia during exercise or in the first minute of recovery). Median baseline BNP levels were 17.5 (12.4-66.4) pg/ml in patients developing scintigraphic ischemia and 45.6 (13.2-107.4) pg/ml in those without ischemia (p = 0.137). The BNP levels increased after exercise (34.4 (15.3-65.4)% increment over baseline, p < 0.001), but the magnitude of this increase was not related to SPECT positivity (35.7 (18.8-65.4)% vs. 27.9 (5.6-64.0)% in patients with and without ischemia, respectively, p = 0.304). No significant association was found between BNP values (at baseline or their change during the test) and ventricular arrhythmias. Plasma BNP values - at baseline or after exercise - were not associated with myocardial ischemia or with ventricular arrhythmia during exercise SPECT. These results highlight the limited usefulness of this biomarker to assess acute ischemia

Optimization of decrementing evoked potential mapping for functional substrate identification in ischaemic ventricular tachycardia ablation

Ventricular tachycardia (VT) ablation approaches based on high-density mapping, which enable the rapid acquisition of thousands of mapping points in order to delineate slow conduction zones, have been widely adopted.1 The identification of functionally relevant substrates has been advanced by the identification of potentials participating in the initiation and/or maintenance of scar-dependent VT. During right ventricular apical (RVA) pacing with an extra-stimulus (S2), these potentials display delayed conduction (decremental) behaviour (DeEP).2 This methodology has been shown to be more specific in identifying the critical isthmus of re-entrant VT.3 An important factor accounting for decrement is conduction velocity (CV) restitution.2 With a short-coupled S2, CV will decrease, and further delay occurs in the near-field signal with respect to the far-field signal, creating DeEPs. Conventionally, the S2 has been delivered at ventricular effective refractory period (VERP) + 20 ms to elicit decrement.3–5 However data are lacking on justifying the delivery of the S2 at VERP + 20 ms, which may result in areas defined as DeEP due to intrinsic CV restitution properties, thus creating larger-than-required ablation target areas. We hypothesized that DeEPs are better identified with longer S2 coupling intervals. The second hypothesis was to consider the definition of a DeEP as the range of decrement beyond 10 ms has not been previously explored and to identify the best combination of these parameters

Omnipolarity applied to equi-spaced electrode array for ventricular tachycardia substrate mapping

Aims : Bipolar electrogram (BiEGM)-based substrate maps are heavily influenced by direction of a wavefront to the mapping bipole. In this study, we evaluate high-resolution, orientation-independent peak-to-peak voltage (Vpp) maps obtained with an equi-spaced electrode array and omnipolar EGMs (OTEGMs), measure its beat-to-beat consistency, and assess its ability to delineate diseased areas within the myocardium compared against traditional BiEGMs on two orientations: along (AL) and across (AC) array splines. Methods and results: The endocardium of the left ventricle of 10 pigs (three healthy and seven infarcted) were each mapped using an Advisor™ HD grid with a research EnSite Precision™ system. Cardiac magnetic resonance images with late gadolinium enhancement were registered with electroanatomical maps and were used for gross scar delineation. Over healthy areas, OTEGM Vpp values are larger than AL bipoles by 27% and AC bipoles by 26%, and over infarcted areas OTEGM Vpp values are 23% larger than AL bipoles and 27% larger than AC bipoles (P < 0.05). Omnipolar EGM voltage maps were 37% denser than BiEGM maps. In addition, OTEGM Vpp values are more consistent than bipolar Vpps showing less beat-by-beat variation than BiEGM by 39% and 47% over both infarcted and healthy areas, respectively (P < 0.01). Omnipolar EGM better delineate infarcted areas than traditional BiEGMs from both orientations. Conclusion: An equi-spaced electrode grid when combined with omnipolar methodology yielded the largest detectable bipolar-like voltage and is void of directional influences, providing reliable voltage assessment within infarcted and non-infarcted regions of the heart.This work was funded by Abbott Laboratories, St. Paul, MN, USA.S

The Atrioventricular Conduction Axis and its Implications for Permanent Pacing

Extensive knowledge of the anatomy of the atrioventricular conduction axis, and its branches, is key to the success of permanent physiological pacing, either by capturing the His bundle, the left bundle branch or the adjacent septal regions. The inter-individual variability of the axis plays an important role in underscoring the technical difficulties known to exist in achieving a stable position of the stimulating leads. In this review, the key anatomical features of the location of the axis relative to the triangle of Koch, the aortic root, the inferior pyramidal space and the inferoseptal recess are summarised. In keeping with the increasing number of implants aimed at targeting the environs of the left bundle branch, an extensive review of the known variability in the pattern of ramification of the left bundle branch from the axis is included. This permits the authors to summarise in a pragmatic fashion the most relevant aspects to be taken into account when seeking to successfully deploy a permanent pacing lead.Sin financiaciónNo data JCR 20211.035 Q1 SJR 2021No data IDR 2021UE

Unexpected impairment of INa underpins reentrant arrhythmias in a knock-in swine model of Timothy syndrome

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Behavioral characterization of a mouse model overexpressing DSCR1/ RCAN1

DSCR1/ RCAN1 is a chromosome 21 gene found to be overexpressed in the brains of Down syndrome (DS) and postulated as a good candidate to contribute to mental disability. However, even though Rcan1 knockout mice have pronounced spatial learning and memory deficits, the possible deleterious effects of its overexpression in DS are not well understood. We have generated a transgenic mouse model overexpressing DSCR1/RCAN1 in the brain and analyzed the effect of RCAN1 overexpression on cognitive function. TgRCAN1 mice present a marked disruption of the learning process in a visuo-spatial learning task. However, no significant differences were observed in the performance of the memory phase of the test (removal session) nor in a step-down passive avoidance task, thus suggesting that once learning has been established, the animals are able to consolidate the information in the longer term

Incidence, clinical characteristics, risk factors and outcomes of meningoencephalitis in patients with COVID-19

We investigated the incidence, clinical characteristics, risk factors, and outcome of meningoencephalitis (ME) in patients with COVID-19 attending emergency departments (ED), before hospitalization. We retrospectively reviewed all COVID patients diagnosed with ME in 61 Spanish EDs (20% of Spanish EDs, COVID-ME) during the COVID pandemic. We formed two control groups: non-COVID patients with ME (non-COVID-ME) and COVID patients without ME (COVID-non-ME). Unadjusted comparisons between cases and controls were performed regarding 57 baseline and clinical characteristics and 4 outcomes. Cerebrospinal fluid (CSF) biochemical and serologic findings of COVID-ME and non-COVID-ME were also investigated. We identified 29 ME in 71,904 patients with COVID-19 attending EDs (0.40‰, 95%CI=0.27-0.58). This incidence was higher than that observed in non-COVID patients (150/1,358,134, 0.11‰, 95%CI=0.09-0.13; OR=3.65, 95%CI=2.45-5.44). With respect to non-COVID-ME, COVID-ME more frequently had dyspnea and chest X-ray abnormalities, and neck stiffness was less frequent (OR=0.3, 95%CI=0.1-0.9). In 69.0% of COVID-ME, CSF cells were predominantly lymphocytes, and SARS-CoV-2 antigen was detected by RT-PCR in 1 patient. The clinical characteristics associated with a higher risk of presenting ME in COVID patients were vomiting (OR=3.7, 95%CI=1.4-10.2), headache (OR=24.7, 95%CI=10.2-60.1), and altered mental status (OR=12.9, 95%CI=6.6-25.0). COVID-ME patients had a higher in-hospital mortality than non-COVID-ME patients (OR=2.26; 95%CI=1.04-4.48), and a higher need for hospitalization (OR=8.02; 95%CI=1.19-66.7) and intensive care admission (OR=5.89; 95%CI=3.12-11.14) than COVID-non-ME patients. ME is an unusual form of COVID presentation (<0.5‰ cases), but is more than 4-fold more frequent than in non-COVID patients attending the ED. As the majority of these MEs had lymphocytic predominance and in one patient SARS-CoV-2 antigen was detected in CSF, SARS-CoV-2 could be the cause of most of the cases observed. COVID-ME patients had a higher unadjusted in-hospital mortality than non-COVID-ME patients

Ventricular tachycardia (VT): Mortality implications in patients with cardiomyopathy, impact of VT ablation and development of new invasive treatment strategies

[eng] BACKGROUND: Ventricular tachycardia (VT) is a common complication affecting patients with structural heart disease and poor left ventricular systolic function. Its occurrence is linked to increased mortality despite treatment with an implantable cardioverter defibrillator (ICD) and there are several challenges that are still to be solved. This thesis will focus on 4 unanswered aspects of the management of VT in a translational fashion, encompassing large registry data and cohort studies, development of new mapping tools in humans and validation of novel electrograms in a preclinical swine model. These advancements will add knowledge to the field of this complex and deadly arrhythmia. HYPOTHESES AND OBJECTIVES: 1) To assess the prognostic impact of ICD therapies in secondary prevention patients suffering VT. 2) To quantify the healthcare usage of patients treated with catheter ablation for recurrent VT compared to medical management. 3) To establish a mechanistic VT ablation guided by decrement evoked potential (DEEP) mapping. 4) To prove that omnipolar EGMs used in vivo identify the substrate of VT accurately and without the directional influences that affect bipolar EGMs. METHODOLOGY: 1) Retrospective analysis of the Ontario ICD database and Cox-regression modeling to quantify independent risk factors for mortality in 7020 ICD recipients. 2) Propensity-matched analysis of catheter ablation versus medical management of 100 matched patients. 3) Multicenter prospective study of VT substrate mapping for the detection of DEEP regions in the VT substrate and its correlation to activation mapping and clinical outcomes. 4) Preclinical swine model of ventricular substrate to explore the utility of direction-independent omnipolar EGMs. RESULTS: 1) Patients treated with secondary prevention ICDs are exposed to an increased mortality after experiencing a life-saving ICD intervention (Antitachycardia pacing, namely ATP or shocks). 2) Patients with symptomatic recurrent VT treated with VT ablation experience a similar healthcare consumption compared to patients treated medically. 3) A mechanistic substrate mapping and ablation strategy targeting DEEP is highly specific for the detection of the critical regions of the VT circuit without the need to induce it. 4) The use of orientation-independent Omnipolar EGMs provide a reliable and physiological way of mapping with higher peak to peak voltages compared to any bipolar EGMs. CONCLUSIONS: The mortality impact of ICD interventions spans from primary to secondary prevention patients. Managing VT ablation invasively yields a decrease in VT burden with respect to the pre-ablation state without incurring in increased healthcare costs when compared to medical treatment. Mechanistic DEEP mapping is a useful tool to assess the VT substrate. Omnipolar EGMs provide a good physiological representation of the VT substrate in a preclinical swine model.[spa] INTRODUCCIÓN: La taquicardia ventricular (TV) es una complicación frecuente en la evolución de los pacientes con miocardiopatía y disfunción sistólica del ventrículo izquierdo. Su aparición se asocia a mayor mortalidad a pesar del tratamiento preventivo con un desfibrilador automático implantable (DAI) y su manejo presenta aún importantes limitaciones. Esta tesis abordará diversos aspectos sobre el abordaje de estos pacientes desde un punto de vista translacional, con estudios de cohortes y con el desarrollo de nuevas herramientas que pueden asociarse a mejores resultados clínicos. OBJETIVOS: 1) Analizar el impacto pronóstico de las terapias apropiadas de DAI en pacientes tratados en prevención secundaria. 2) Cuantificar el consumo sanitario y tasas de reingresos en pacientes comparables con TV recurrente tratados médicamente frente a ablación con catéter. 3) Establecer el uso de la ablación de TV guiada por potenciales de conducción decremental (DEEP). 4) Probar la utilidad de electrogramas omnipolares para el mapeo de sustrato ventricular in vivo para valorar su independencia del frente de activación. METODOLOGÍA: 1) Análisis retrospectivo del registro de DAI de Ontario y uso de modelo de regresión de Cox para cuantificar los factores de riesgo independientes de mortalidad en 7020 pacientes con DAI. 2) Análisis de tasa de reingresos de pacientes con TV recurrente tratados con ablación con catéter frente a tratamiento médico. 3) Estudio de intervención multicéntrico con ablación de TV guiada por potenciales de conducción decremental (DEEP) y su correlación con mapeo de activación y los resultados clínicos. 4) Estudio de un modelo preclínico porcino de sustrato de TV con electrogramas omnipolares y su utilidad frente a electrogramas convencionales. RESULTADOS: 1) La población tratada en prevención secundaria con un DAI presenta un incremento de mortalidad a largo plazo tras sufrir terapias apropiadas. 2) Los pacientes afectos de TV recurrente intervenidos mediante ablación con catéter presentan una tasa de reingresos similar a los pacientes tratados médicamente. 3) La estrategia mecanística de ablación guiada por potenciales de conducción decremental es muy específica para la detección del circuito de TV sin necesidad de provocarla. 4) El uso de electrogramas omnipolares proporciona mayores voltajes que cualquier configuración bipolar. CONCLUSIONES: El impacto sobre la mortalidad de la TV es notable tanto en pacientes con DAI en prevención primaria como secundaria. El tratamiento invasivo con catéter para TV disminuye los reingresos hospitalarios respecto al periodo pre-ablación sin incurrir en aumento del consumo sanitario global. El mapeo mecanístico con potenciales de conducción decremental es una estrategia con alto valor añadido para el estudio del sustrato de TV. Los electrogramas omnipolares reflejan con alta fidelidad fisiológica el sustrato de TV en un modelo preclínico porcino