Publications by authors named "Martin Aguilar"

61 Publications

The Rapidly-Developing Area of Radiocardiology: Principles, Complications and Applications of Radiotherapy on the Heart.

Can J Cardiol 2021 Jul 22. Epub 2021 Jul 22.

Department of Medicine and Research Center, Montreal Heart Institute and Université de Montréal; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Ventricular arrhythmias are the leading cause of sudden cardiac death. Current treatment strategies for VT, including antiarrhythmic drugs and catheter ablation, have limited efficacy in patients with structural heart disease. Non-invasive ablation with the use of externally applied radiation (cardiac radio-ablation) has emerged as a promising and novel approach to treating recurrent VTs. However, the heart is generally an "organ at risk" for radiation treatments, such that very little is known on the effects of radiotherapy on cardiac ultrastructure and electrophysiological properties. Furthermore, there has been limited interaction between the fields of cardiology and radiation oncology and physics. The advent of cardiac radio-ablation will undoubtedly increase interactions between cardiologists, cardiac electrophysiologists, radiation oncologists and physicists There is an important knowledge gap separating these specialties while scientific developments, technical optimization and improvements are dependent on intense multidisciplinary collaboration. This manuscript seeks to review the basic of radiation physics and biology for cardiovascular specialists in an effort to facilitate constructive scientific and clinical collaborations to improve patient outcomes.
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http://dx.doi.org/10.1016/j.cjca.2021.07.011DOI Listing
July 2021

Serum Contactin-1 in CIDP: A Cross-Sectional Study.

Neurol Neuroimmunol Neuroinflamm 2021 Jul 20;8(5). Epub 2021 Jul 20.

From the Department of Neurology and Neurophysiology (L.W., C.V., F.E.), Amsterdam Neuroscience, Amsterdam UMC, Location AMC, Amsterdam, the Netherlands; Neuromuscular Diseases Unit (L.M.-A., C.L., L.Q.), Department of Neurology, Hospital de La Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain; Department of Clinical Neurosciences (J.F., S.R.), West Wing, John Radcliffe Hospital, Oxford, United Kingdom; Neurochemistry Lab (M.J.A.K.-S., C.E.T.), Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands; and Department of Neurology (M.C., Z.L., J.K.), Amsterdam Neuroscience, Amsterdam UMC, Location VU Medical Center, Amsterdam, the Netherlands.

Objective: To investigate whether serum levels of contactin-1, a paranodal protein, correlate with paranodal injury as seen in patients with CIDP with antibodies targeting the paranodal region.

Methods: Serum contactin-1 levels were measured in 187 patients with CIDP and 222 healthy controls. Paranodal antibodies were investigated in all patients.

Results: Serum contactin-1 levels were lower in patients (N = 41) with paranodal antibodies compared with patients (N = 146) without paranodal antibodies ( < 0.01) and showed good discrimination between these groups (area under the curve 0.84; 95% CI: 0.76-0.93).

Conclusions: These findings suggest that serum contactin-1 levels have the potential to serve as a possible diagnostic biomarker of paranodal injury in CIDP.

Classification Of Evidence: This study provides class II evidence that serum contactin-1 levels can discriminate between patients with CIDP with or without paranodal antibodies with a sensitivity of 71% (95% CI: 56%-85%) and a specificity of 97% (95% CI: 83%-100%).
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http://dx.doi.org/10.1212/NXI.0000000000001040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293285PMC
July 2021

Intravenous immunoglobulin treatment for mild Guillain-Barré syndrome: an international observational study.

J Neurol Neurosurg Psychiatry 2021 Jun 8. Epub 2021 Jun 8.

Department of Neurology, Erasmus MC, Rotterdam, The Netherlands

Objective: To compare the disease course in patients with mild Guillain-Barré syndrome (GBS) who were treated with intravenous immunoglobulin (IVIg) or supportive care only.

Methods: We selected patients from the prospective observational International GBS Outcome Study (IGOS) who were able to walk independently at study entry (mild GBS), treated with one IVIg course or supportive care. The primary endpoint was the GBS disability score four weeks after study entry, assessed by multivariable ordinal regression analysis.

Results: Of 188 eligible patients, 148 (79%) were treated with IVIg and 40 (21%) with supportive care. The IVIg group was more disabled at baseline. IVIg treatment was not associated with lower GBS disability scores at 4 weeks (adjusted OR (aOR) 1.62, 95% CI 0.63 to 4.13). Nearly all secondary endpoints showed no benefit from IVIg, although the time to regain full muscle strength was shorter (28 vs 56 days, p=0.03) and reported pain at 26 weeks was lower (n=26/121, 22% vs n=12/30, 40%, p=0.04) in the IVIg treated patients. In the subanalysis with persistent mild GBS in the first 2 weeks, the aOR for a lower GBS disability score at 4 weeks was 2.32 (95% CI 0.76 to 7.13). At 1 year, 40% of all patients had residual symptoms.

Conclusion: In patients with mild GBS, one course of IVIg did not improve the overall disease course. The certainty of this conclusion is limited by confounding factors, selection bias and wide confidence limits. Residual symptoms were often present after one year, indicating the need for better treatments in mild GBS.
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http://dx.doi.org/10.1136/jnnp-2020-325815DOI Listing
June 2021

Antibodies to the Caspr1/contactin-1 complex in chronic inflammatory demyelinating polyradiculoneuropathy.

Brain 2021 May;144(4):1183-1196

Neuromuscular Diseases Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.

Previous studies have described the clinical, serological and pathological features of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and antibodies directed against the paranodal proteins neurofascin-155, contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), or nodal forms of neurofascin. Such antibodies are useful for diagnosis and potentially treatment selection. However, antibodies targeting Caspr1 only or the Caspr1/CNTN1 complex have been reported in few patients with CIDP. Moreover, it is unclear if these patients belong to the same pathophysiological subgroup. Using cell-based assays in routine clinical testing, we identified sera from patients with CIDP showing strong membrane reactivity when both CNTN1 and Caspr1 were co-transfected (but not when CNTN1 was transfected alone). Fifteen patients (10 male; aged between 40 and 75) with antibodies targeting Caspr1/CNTN1 co-transfected cells were enrolled for characterization. The prevalence of anti-Caspr1/CNTN1 antibodies was 1.9% (1/52) in the Sant Pau CIDP cohort, and 4.3% (1/23) in a German cohort of acute-onset CIDP. All patients fulfilled European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite diagnostic criteria for CIDP. Seven (47%) were initially diagnosed with Guillain-Barré syndrome due to an acute-subacute onset. Six (40%) patients had cranial nerve involvement, eight (53%) reported neuropathic pain and 12 (80%) ataxia. Axonal involvement and acute denervation were frequent in electrophysiological studies. Complete response to intravenous immunoglobulin was not observed, while most (90%) responded well to rituximab. Enzyme-linked immunosorbent assay (ELISA) and teased nerve fibre immunohistochemistry confirmed reactivity against the paranodal Caspr1/CNTN1 complex. Weaker reactivity against Caspr1 transfected alone was also detected in 10/15 (67%). Sera from 13 of these patients were available for testing by ELISA. All 13 samples reacted against Caspr1 by ELISA and this reactivity was enhanced when CNTN1 was added to the Caspr1 ELISA. IgG subclasses were also investigated by ELISA. IgG4 was the predominant subclass in 10 patients, while IgG3 was predominant in other three patients. In conclusion, patients with antibodies to the Caspr1/CNTN1 complex display similar serological and clinical features and constitute a single subgroup within the CIDP syndrome. These antibodies likely target Caspr1 primarily and are detected with Caspr1-only ELISA, but reactivity is optimal when CNTN1 is added to Caspr1 in cell-based assays and ELISA.
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http://dx.doi.org/10.1093/brain/awab014DOI Listing
May 2021

Catheter ablation of short-coupled variant of torsade de pointes.

Clin Res Cardiol 2021 Mar 26. Epub 2021 Mar 26.

Department of Cardiology and Angiology, Märkische Kliniken GmbH, Klinikum Luedenscheid, Luedenscheid, Germany.

Background: The short-coupled variant of torsade de pointes (sc-TdP) is a malignant arrhythmia that frequently presents with ventricular fibrillation (VF) electrical storm. Verapamil is considered the first-line therapy of sc-TdP while catheter ablation is not widely adopted. The aim of this study was to determine the origin of sc-TdP and to assess the outcome of catheter ablation using 3D-mapping.

Methods And Results: We retrospectively analyzed five patients with sc-TdP who underwent 3D-mapping and ablation of sc-TdP at five different institutions. Four patients initially presented with sudden cardiac arrest, one patient experienced recurrent syncope as the first manifestation. All patients demonstrated a monomorphic premature ventricular contraction (PVC) with late transition left bundle branch block pattern, superior axis, and a coupling interval of less than 300 ms. triggering recurrent TdP and VF. In four patients, the culprit PVC was mapped to the free wall insertion of the moderator band (MB) with a preceding Purkinje potential in two patients. Catheter ablation using 3D-mapping and intracardiac echocardiography eliminated sc-TdP in all patients, with no recurrence at mean 2.7 years (range 6 months to 8 years) of follow-up.

Conclusion: 3D-mapping and intracardiac echocardiography demonstrate that sc-TdP predominantly originates from the MB free wall insertion and its Purkinje network. Catheter ablation of the culprit PVC at the MB free wall junction leads to excellent short- and long-term results and should be considered as first-line therapy in recurrent sc-TdP or electrical storm.
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http://dx.doi.org/10.1007/s00392-021-01840-zDOI Listing
March 2021

New aspects of endocrine control of atrial fibrillation and possibilities for clinical translation.

Cardiovasc Res 2021 Jun;117(7):1645-1661

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, UK.

Hormones are potent endo-, para-, and autocrine endogenous regulators of the function of multiple organs, including the heart. Endocrine dysfunction promotes a number of cardiovascular diseases, including atrial fibrillation (AF). While the heart is a target for endocrine regulation, it is also an active endocrine organ itself, secreting a number of important bioactive hormones that convey significant endocrine effects, but also through para-/autocrine actions, actively participate in cardiac self-regulation. The hormones regulating heart-function work in concert to support myocardial performance. AF is a serious clinical problem associated with increased morbidity and mortality, mainly due to stroke and heart failure. Current therapies for AF remain inadequate. AF is characterized by altered atrial function and structure, including electrical and profibrotic remodelling in the atria and ventricles, which facilitates AF progression and hampers its treatment. Although features of this remodelling are well-established and its mechanisms are partly understood, important pathways pertinent to AF arrhythmogenesis are still unidentified. The discovery of these missing pathways has the potential to lead to therapeutic breakthroughs. Endocrine dysfunction is well-recognized to lead to AF. In this review, we discuss endocrine and cardiocrine signalling systems that directly, or as a consequence of an underlying cardiac pathology, contribute to AF pathogenesis. More specifically, we consider the roles of products from the hypothalamic-pituitary axis, the adrenal glands, adipose tissue, the renin-angiotensin system, atrial cardiomyocytes, and the thyroid gland in controlling atrial electrical and structural properties. The influence of endocrine/paracrine dysfunction on AF risk and mechanisms is evaluated and discussed. We focus on the most recent findings and reflect on the potential of translating them into clinical application.
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http://dx.doi.org/10.1093/cvr/cvab080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208746PMC
June 2021

M/M/Infinity Birth-Death Processes - A Quantitative Representational Framework to Summarize and Explain Phase Singularity and Wavelet Dynamics in Atrial Fibrillation.

Front Physiol 2020 14;11:616866. Epub 2021 Jan 14.

College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.

Rationale: A quantitative framework to summarize and explain the quasi-stationary population dynamics of unstable phase singularities (PS) and wavelets in human atrial fibrillation (AF) is at present lacking. Building on recent evidence showing that the formation and destruction of PS and wavelets in AF can be represented as renewal processes, we sought to establish such a quantitative framework, which could also potentially provide insight into the mechanisms of spontaneous AF termination.

Objectives: Here, we hypothesized that the observed number of PS or wavelets in AF could be governed by a common set of renewal rate constants λ (for PS or wavelet formation) and λ (PS or wavelet destruction), with steady-state population dynamics modeled as an M/M/∞ birth-death process. We further hypothesized that changes to the M/M/∞ birth-death matrix would explain spontaneous AF termination.

Methods And Results: AF was studied in in a multimodality, multispecies study in humans, animal experimental models (rats and sheep) and Ramirez-Nattel-Courtemanche model computer simulations. We demonstrated: (i) that λ and λ can be combined in a Markov M/M/∞ process to accurately model the observed average number and population distribution of PS and wavelets in all systems at different scales of mapping; and (ii) that slowing of the rate constants λ and λ is associated with slower mixing rates of the M/M/∞ birth-death matrix, providing an explanation for spontaneous AF termination.

Conclusion: M/M/∞ birth-death processes provide an accurate quantitative representational architecture to characterize PS and wavelet population dynamics in AF, by providing governing equations to understand the regeneration of PS and wavelets during sustained AF, as well as providing insight into the mechanism of spontaneous AF termination.
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http://dx.doi.org/10.3389/fphys.2020.616866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841497PMC
January 2021

Postoperative Atrial Fibrillation: Features, Mechanisms, and Clinical Management.

Card Electrophysiol Clin 2021 03;13(1):123-132

Department of Medicine and Research Center, Montreal Heart Institute and Université de Montréal, 5000 Belanger Street, Montréal, Québec H1T 1C8, Canada; Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Hufelandstr. 55, Essen 45122, Germany; IHU LIRYC and Fondation Bordeaux Université, Bordeaux, France.

Advances in atrial fibrillation (AF) management, perioperative medicine, and surgical techniques have reignited an interest in postoperative AF (POAF). POAF results from the interaction among subclinical atrial substrate, surgery-induced substrate, and transient postoperative factors. Prophylaxis for POAF after cardiac surgery is well established but the indications for preoperative treatment in noncardiac surgery need further investigation. A rate-control strategy is adequate for most asymptomatic patients with POAF and anticoagulation should be initiated for POAF more than 48 to 72 hours postsurgery. Research is needed to improve evidence-based management of POAF and guide long-term management in view of the substantial late recurrence-rate.
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http://dx.doi.org/10.1016/j.ccep.2020.11.010DOI Listing
March 2021

One Ring to Rule Them All: Continuous Monitoring of Patients With Secondary Atrial Fibrillation Points to a Unifying Underlying Mechanism.

Can J Cardiol 2021 May 23;37(5):686-689. Epub 2021 Jan 23.

Department of Medicine and Research Centre, Montréal Heart Institute and University of Montréal, Montréal, Québec, Canada; Institute of Pharmacology, West German Heart and Vascular Center, University of Duisburg-Essen, Essen, Germany; L'Institut Hospitalo-Universitaire L'Institut de Rythmologie et Modélisation Cardiaque (IHU LIRYC) and Fondation Bordeaux Université Bordeaux, Bordeaux, France. Electronic address:

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http://dx.doi.org/10.1016/j.cjca.2021.01.018DOI Listing
May 2021

Sorafenib as a second-line treatment in metastatic renal cell carcinoma in Mexico: a prospective cohort study.

BMC Cancer 2021 Jan 5;21(1):16. Epub 2021 Jan 5.

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Dominguez Sección XVI, 14080, Mexico City, PC, Mexico.

Background: Sequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with metastatic renal cell carcinoma (RCC). Our aim was to determine the activity and tolerability of sorafenib as a second-line therapy in advanced RCC initially treated with a different VEGF-tyrosine kinase inhibitor (TKI).

Methods: A prospective observational cohort in Mexico (2012-2019). We included 132 subjects with metastatic RCC and who had progression despite treatment with sunitinib. The primary end-point was time to disease progression as evaluated every 12-16 weeks.

Results: The mean age of the cohort was 59 years (interquartile range [IQR] 50-72), 96 (73%) were men, and 48 (36%) had a favorable prognosis according to the IMDC (International Metastatic RCC Database Consortium) prognostic model. The median progression-free survival (PFS) and overall-survival after the introduction of sorafenib treatment was 8.6 months (95% confidence interval [CI]: 6.7-10.5) and 40 months (95% CI: 34.5-45.4) respectively. The median overall survival from RCC diagnosis to death was 71 months (95% CI: 58.2-83.8). On multivariable analyses, age > 65 years was associated with a longer PFS (HR 0.51; 95% CI: 0.31-0.86; p = 0.018). The median PFS in subjects aged > 65 years was longer compared to subjects ≤65 years (14.0 [95% CI: 9.2-18.8] vs. 7.2 months [95% CI: 5.3-9.1]; p = 0.012). Adverse events grade ≥ 3 associated with sorafenib occurred in 38 (29%) patients.

Conclusion: Sequential inhibition of VEGF with sorafenib as a second-line treatment may benefit patients with metastatic RCC, especially in subjects > 65 years old.
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http://dx.doi.org/10.1186/s12885-020-07720-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786959PMC
January 2021

Catheter ablation of ventricular tachycardia in patients with prior cardiac surgery: An analysis from the International VT Ablation Center Collaborative Group.

J Cardiovasc Electrophysiol 2021 Feb 24;32(2):409-416. Epub 2021 Jan 24.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Introduction: Patients with prior cardiac surgery may represent a subgroup of patients with ventricular tachycardia (VT) that may be more difficult to control with catheter ablation.

Methods: We evaluated 1901 patients with ischemic and nonischemic cardiomyopathy who underwent VT ablation at 12 centers. Clinical characteristics and VT radiofrequency ablation procedural outcomes were assessed and compared between those with and without prior cardiac surgery. Kaplan-Meier analysis was used to estimate freedom from recurrent VT and survival.

Results: There were 578 subjects (30.4%) with prior cardiac surgery identified in the cohort. Those with prior cardiac surgery were older (66.4 ± 11.0 years vs. 60.5 ± 13.9 years, p < .01), with lower left ventricular ejection fraction (30.2 ± 11.5% vs. 34.8 ± 13.6%, p < .01) and more ischemic heart disease (82.5% vs. 39.3%, p < .01) but less likely to undergo epicardial mapping or ablation (9.0% vs. 38.1%, p<.01) compared to those without prior surgery. When epicardial mapping was performed, a significantly greater proportion required surgical intervention for access (19/52 [36.5%] vs. 14/504 [2.8%]; p < .01). Procedural complications, including epicardial access-related complications, were lower (5.7% vs. 7.0%, p < .01) in patients with versus without prior cardiac surgery. VT-free survival (75.1% vs. 74.1%, p = .805) and survival (86.5% vs. 87.9%, p = .397) were not different between those with and without prior heart surgery, regardless of etiology of cardiomyopathy. VT recurrence was associated with increased mortality in patients with and without prior cardiac surgery.

Conclusion: Despite different clinical characteristics and fewer epicardial procedures, the safety and efficacy of VT ablation in patients with prior cardiac surgery is similar to others in this cohort. The incremental yield of epicardial mapping in predominant ischemic cardiomyopathy population prior heart surgery may be low but appears safe in experienced centers.
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http://dx.doi.org/10.1111/jce.14849DOI Listing
February 2021

Do Atrial Fibrillation-Promoting Gene Variants Act by Enhancing Atrial Remodeling?

JACC Clin Electrophysiol 2020 11;6(12):1522-1524

Department of Medicine and Research Center, Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada.

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http://dx.doi.org/10.1016/j.jacep.2020.07.008DOI Listing
November 2020

The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation.

Can J Cardiol 2020 12 22;36(12):1847-1948. Epub 2020 Oct 22.

Institut de Cardiologie de Montréal, Université de Montréal, Montréal, Québec, Canada.

The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, since 2010 a large number of developments had accumulated in a wide range of areas, motivating the committee to complete a thorough guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to evaluate recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.
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http://dx.doi.org/10.1016/j.cjca.2020.09.001DOI Listing
December 2020

Pulmonary Vein Stenosis After Atrial Fibrillation Ablation: Insights From the ADVICE Trial.

Can J Cardiol 2020 12 3;36(12):1965-1974. Epub 2020 Nov 3.

Montreal Health Innovations Coordinating Center (MHICC), Montreal, Quebec, Canada.

Background: Pulmonary vein (PV) stenosis is a complication of atrial fibrillation (AF) ablation. The incidence of PV stenosis after routine post-ablation imaging remains unclear and is limited to single-centre studies. Our objective was to determine the incidence and predictors of PV stenosis following circumferential radiofrequency ablation in the multicentre Adenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination (ADVICE) trial.

Methods: Patients with symptomatic AF underwent circumferential radiofrequency ablation in one of 13 trial centres. Computed tomographic (CTA) or magnetic resonance (MRA) angiography was performed before ablation and 90 days after ablation. Two blinded reviewers measured PV diameters and areas. PVs with stenosis were classified as severe (> 70%), moderate (50%-70%), or mild (< 50%). Predictors of PV stenosis were identified by means of multivariable logistic regression.

Results: A total of 197 patients (median age 59.5 years, 29.4% women) were included in this substudy. PV stenosis was identified in 41 patients (20.8%) and 47 (8.2%) of 573 ablated PVs. PV stenosis was classified as mild in 42 PVs (7.3%) and moderate in 5 PVs (0.9%). No PVs had severe stenosis. Both cross-sectional area and diameter yielded similar classifications for severity of PV stenosis. Diabetes was associated with a statistically significant increased risk of PV stenosis (OR 4.91, 95% CI 1.45-16.66).

Conclusions: In the first systematic multicentre evaluation of post-ablation PV stenosis, no patient acquired severe PV stenosis. Although the results are encouraging for the safety of AF ablation, 20.8% of patients had mild or moderate PV stenosis, in which the long-term effects are unknown.
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http://dx.doi.org/10.1016/j.cjca.2020.10.013DOI Listing
December 2020

Serum neurofilament light chain predicts long-term prognosis in Guillain-Barré syndrome patients.

J Neurol Neurosurg Psychiatry 2020 Nov 5. Epub 2020 Nov 5.

Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

Objective: To study baseline serum neurofilament light chain (sNfL) levels as a prognostic biomarker in Guillain-Barré syndrome (GBS).

Methods: We measured NfL in serum (98 samples) and cerebrospinal fluid (CSF) (24 samples) of patients with GBS prospectively included in the International GBS Outcome Study (IGOS) in Spain using single-molecule array (SiMoA) and compared them with 53 healthy controls (HCs). We performed multivariable regression to analyse the association between sNfL levels and functional outcome at 1 year.

Results: Patients with GBS had higher NfL levels than HC in serum (55.49 pg/mL vs 9.83 pg/mL, p<0.0001) and CSF (1308.5 pg/mL vs 440.24 pg/mL, p=0.034). Patients with preceding diarrhoea had higher sNfL than patients with respiratory symptoms or no preceding infection (134.90 pg/mL vs 47.86 pg/mL vs 38.02 pg/mL, p=0.016). sNfL levels correlated with Guillain-Barré Syndrome Disability Score and Inflammatory Rasch-built Overall Disability Scale (I-RODS) at every timepoint. Patients with pure motor variant and Miller Fisher syndrome showed higher sNfL levels than patients with sensorimotor GBS (162.18 pg/mL vs 95.50 pg/mL vs 38.02 pg/mL, p=0.025). Patients with acute motor axonal neuropathy cute motor axonal neuropathy had higher sNfL levels than other variants (190.55 pg/mL vs 46.79 pg/mL, p=0.013). sNfL returned to normal levels at 1 year. High baseline sNfL levels were associated with inability to run (OR=1.65, 95% CI 1.14 to 2.40, p=0.009) and lower I-RODS (β -2.60, 95% CI -4.66 to -0.54, p=0.014) at 1 year. Cut-off points predicting clinically relevant outcomes at 1 year with high specificity were calculated: inability to walk independently (>319 pg/mL), inability to run (>248 pg/mL) and ability to run (<34 pg/mL).

Conclusion: Baseline sNfL levels are increased in patients with GBS, are associated with disease severity and axonal variants and have an independent prognostic value in patients with GBS.
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http://dx.doi.org/10.1136/jnnp-2020-323899DOI Listing
November 2020

Electrophysiological Effects of Atrial Epicardial Adipose Tissue: Keep Your Friends Close and Your Enemies Closer.

J Am Coll Cardiol 2020 09;76(10):1212-1214

Department of Medicine and Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.

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http://dx.doi.org/10.1016/j.jacc.2020.07.031DOI Listing
September 2020

Immune effector cell-associated neurotoxicity syndrome: A therapeutic approach in the critically ill.

Med Intensiva (Engl Ed) 2020 Aug 29. Epub 2020 Aug 29.

Servicio de Medicina Intensiva, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España.

Immunotherapy with chimeric antigen-specific receptor modified T cells, known as CAR-T, is emerging as a promising approach to hematological malignancies. In this regard, CAR-T against human cluster of differentiation (CD) 19 has demonstrated antitumor efficacy in application to B cell neoplasms resistant to conventional therapy. However, activation of the immune system induces severe and specific complications which can prove life-threatening. These include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (known as ICANS) - the latter being the subject of the present review. Although the physiopathological mechanisms underlying ICANS are not well known, a number of clinical and biological factors increase the risk of developing neurotoxicity associated to CAR-T therapy. Treatment is based on close monitoring, measures of support, anticonvulsivants, corticosteroids, and early admission to intensive care. The present study offers a comprehensive review of the available literature from a multidisciplinary perspective, including recommendations from intensivists, neurologists and hematologists dedicated to the care of critically ill adults.
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http://dx.doi.org/10.1016/j.medin.2020.06.014DOI Listing
August 2020

Syncope after successful implantation of atrioventricular synchronous leadless pacemaker caused by polymorphic ventricular tachycardia.

HeartRhythm Case Rep 2020 Aug 18;6(8):503-506. Epub 2020 May 18.

Cardiac Electrophysiology Department, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1016/j.hrcr.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424308PMC
August 2020

Epicardial Ablation of Supraventricular Tachycardias.

Card Electrophysiol Clin 2020 09 27;12(3):357-369. Epub 2020 Jun 27.

Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA; Harvard Medical School; Clinical Cardiac Electrophysiology Fellowship; Ventricular Arrhythmia Program. Electronic address:

Supraventricular arrhythmias are the most common cardiac arrhythmias encountered; however, it is uncommon that supraventricular tachycardias require percutaneous epicardial access for successful mapping and ablation. There are particular scenarios where epicardial access and ablation should be considered. Certain accessory pathways particularly in the posteroseptal region may require epicardial access for successful ablation. These pathways may also be approached from within the coronary sinus system. In addition, tachycardias near the phrenic nerve in the right atrium or left atrium may require epicardial access for successful ablation or to allow displacement of the phrenic nerve facilitating safe catheter ablation.
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http://dx.doi.org/10.1016/j.ccep.2020.05.001DOI Listing
September 2020

Recurrent ventricular tachycardia arising at the treatment borderzone after stereotactic radioablation in a patient with ischemic cardiomyopathy.

Europace 2020 07;22(7):1053

Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.

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http://dx.doi.org/10.1093/europace/euaa077DOI Listing
July 2020

Direct Thrombin Inhibitors as an Alternative to Heparin During Catheter Ablation: A Multicenter Experience.

JACC Clin Electrophysiol 2020 05 26;6(5):484-490. Epub 2020 Feb 26.

Division of Cardiology, University of California San Francisco, San Francisco, California, USA. Electronic address:

Objectives: The goal of this study was to report a multicenter series of left-sided catheter ablations performed by using intravenous direct thrombin inhibitors (DTIs) as an alternative to heparin.

Background: Amidst a looming worldwide shortage of heparin, there are insufficient data to guide nonheparin-based peri-procedural anticoagulation in patients undergoing catheter ablation.

Methods: This study reviewed all catheter ablations at 6 institutions between 2006 and 2019 to assess the safety and efficacy of DTIs for left-sided radiofrequency catheter ablation of atrial fibrillation and ventricular tachycardia.

Results: In total, 53 patients (age 63.0 ± 9.3 years, 68% male, CHA₂DS₂-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category] score 2.8 ± 1.6, left ventricular ejection fraction 46 ± 15%) underwent ablation with DTIs (75% bivalirudin, 25% argatroban) due to heparin contraindication(s) (72% heparin-induced thrombocytopenia, 21% heparin allergy, 4% protamine reaction, and 4% religious reasons). The patient's usual oral anticoagulant was continued without interruption in 69%. Procedures were performed for atrial fibrillation (64%) or ventricular tachycardia/premature ventricular contractions (36%). Transseptal puncture was undertaken in 81%, and a contact force-sensing catheter was used in 70%. Vascular ultrasound was used in 71%, and femoral arterial access was gained in 36%. A bolus followed by infusion was used in all but 4 cases, and activated clotting time was monitored peri-procedurally in 72%, with 32% receiving additional boluses. Procedure duration was 216 ± 116 min, and ablation time was 51 ± 22 min. No major bleeding or embolic complications were observed. Four patients had minor self-limiting bleeding complications, including a small pericardial effusion (<1 cm), a small groin hematoma, and hematuria.

Conclusions: In this multicenter series, intravenous DTIs were safely used as an alternative to heparin for left-sided catheter ablation.
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http://dx.doi.org/10.1016/j.jacep.2019.12.003DOI Listing
May 2020

Unintentional magnet reversion of an implanted cardiac defibrillator by an electronic cigarette.

HeartRhythm Case Rep 2020 Mar 16;6(3):121-123. Epub 2020 Mar 16.

Cardiovascular Arrhythmia Service, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1016/j.hrcr.2020.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076322PMC
March 2020

[Clinical characteristics of patients with stroke code activation not identified by the emergency medical service].

Rev Neurol 2020 Apr;70(7):251-256

Hospital Universitari Germans Trias i Pujol, 08916 Badalona, España.

Aims: To determine the sensitivity of stroke detection by emergency medical services (EMS) and to analyse the clinical characteristics of unidentified patients with suspected stroke.

Patients And Methods: Prospective register of patients with suspected stroke in our area (850,000 inhabitants) from 2011 to 2017. The population that notified the EMS was selected. Of this population, patients with and without stroke code activation by the EMS were compared (EMS+ versus EMS-). Demographics, time to progression, clinical characteristics of the episode and reperfusion therapy administered were recorded.

Results: Of a total of 5,497 patients with suspected stroke, 2,087 alerted the EMS: 1,611 (77%) EMS+ and 476 (33%) EMS-. The EMS- patients presented lower scores on the National Institute of Health Stroke Scale (8 vs. 11) and a greater frequency of clinical features of the vertebrobasilar territory (14.1% vs. 8.7%) and partial hemispheric clinical features (23.5% vs. 18.4%), especially in the left hemisphere (78.1% vs. 48.4%). Reperfusion treatment was administered in 29% of EMS+ and 23% of EMS-. The time from symptom onset to treatment was 42 minutes longer in the EMS group (175 versus 133 minutes).

Conclusions: The sensitivity of EMS to detect stroke patients in our series is 77%. We have identified clinical features associated with lack of sensitivity, such as vertebrobasilar territory symptoms or isolated language disorder.
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http://dx.doi.org/10.33588/rn.7007.2019161DOI Listing
April 2020

Antibodies against nodo-paranodal proteins are not present in genetic neuropathies.

Neurology 2020 07 26;95(4):e427-e433. Epub 2020 Feb 26.

From the Neuromuscular Diseases Unit, Department of Neurology (L.M.-A., E.P.-G., C.L., J.D.-M., E.C.-V., R.R.-G., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona; Department of Neurology (M.F., H.A., T.S.), Hospital Universitari i Politècnic La Fe, Valencia; Service of Neurology (A.C.-A., A.L.P.-N.), University Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander; Centro para la Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (J.D.-M., R.-R.G., L.Q.), Madrid; and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) (A.L.P.-N.), Santander, Spain.

Objective: To study the presence of nodal and paranodal immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in patients with genetic neuropathies.

Methods: A total of 108 patients with genetic neuropathies from 3 different centers were included. The presence of IgG and IgM antibodies against neurofascin-155 (NF155), nodal neurofascin (NF186 and NF140), and contactin-1 (CNTN1) were investigated with a cell-based assay (CBA) using immunocytochemistry in transfected HEK293 cells. Sera with positive or uncertain results were further tested by ELISA and immunohistochemistry in pig teased-nerve fibers.

Results: Six patients with Charcot-Marie-Tooth disease (CMT) had an uncertain staining pattern for IgM against nodal neurofascin that was not confirmed by ELISA. Two patients with CMT had an uncertain staining pattern for IgG against nodal neurofascin that was not confirmed by ELISA or immunohistochemistry. One patient with CMT with a confirmed mutation tested positive for IgG against NF155 by CBA and ELISA (1/900), but was not confirmed by immunohistochemistry and was ultimately classified as negative.

Conclusions: Antibodies against nodal or paranodal antigens were not detected in our cohort of patients with CMT, as previously reported. Some patients may falsely test positive for any of the techniques; confirmatory techniques should be incorporated into the routine testing.
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http://dx.doi.org/10.1212/WNL.0000000000009189DOI Listing
July 2020

Renewal Theory as a Universal Quantitative Framework to Characterize Phase Singularity Regeneration in Mammalian Cardiac Fibrillation.

Circ Arrhythm Electrophysiol 2019 12 9;12(12):e007569. Epub 2019 Dec 9.

College of Medicine and Public Health (D.D., D.C., A.D.M., A.N.G.), Flinders University of South Australia, Adelaide, SA, Australia.

Background: Despite a century of research, no clear quantitative framework exists to model the fundamental processes responsible for the continuous formation and destruction of phase singularities (PS) in cardiac fibrillation. We hypothesized PS formation/destruction in fibrillation could be modeled as self-regenerating Poisson renewal processes, producing exponential distributions of interevent times governed by constant rate parameters defined by the prevailing properties of each system.

Methods: PS formation/destruction were studied in 5 systems: (1) human persistent atrial fibrillation (n=20), (2) tachypaced sheep atrial fibrillation (n=5), (3) rat atrial fibrillation (n=4), (5) rat ventricular fibrillation (n=11), and (5) computer-simulated fibrillation. PS time-to-event data were fitted by exponential probability distribution functions computed using maximum entropy theory, and rates of PS formation and destruction (λ/λ) determined. A systematic review was conducted to cross-validate with source data from literature.

Results: In all systems, PS lifetime and interformation times were consistent with underlying Poisson renewal processes (human: λ, 4.2%/ms±1.1 [95% CI, 4.0-5.0], λ, 4.6%/ms±1.5 [95% CI, 4.3-4.9]; sheep: λ, 4.4%/ms [95% CI, 4.1-4.7], λ, 4.6%/ms±1.4 [95% CI, 4.3-4.8]; rat atrial fibrillation: λ, 33%/ms±8.8 [95% CI, 11-55], λ, 38%/ms [95% CI, 22-55]; rat ventricular fibrillation: λ, 38%/ms±24 [95% CI, 22-55], λ, 46%/ms±21 [95% CI, 31-60]; simulated fibrillation λ, 6.6-8.97%/ms [95% CI, 4.1-6.7]; ≥0.90 in all cases). All PS distributions identified through systematic review were also consistent with an underlying Poisson renewal process.

Conclusions: Poisson renewal theory provides an evolutionarily preserved universal framework to quantify formation and destruction of rotational events in cardiac fibrillation.
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http://dx.doi.org/10.1161/CIRCEP.119.007569DOI Listing
December 2019

Postoperative Atrial Fibrillation After Noncardiac Surgery: Maybe Not So Benign After All.

Can J Cardiol 2019 11 20;35(11):1423-1425. Epub 2019 Aug 20.

Department of Medicine and Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Canada; IHU Liryc and Fondation Bordeaux Université, Bordeaux, France; Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Duisburg, Germany.

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http://dx.doi.org/10.1016/j.cjca.2019.08.013DOI Listing
November 2019

Pharmacotherapy in inherited and acquired ventricular arrhythmia in structurally normal adult hearts.

Expert Opin Pharmacother 2019 Dec 30;20(17):2101-2114. Epub 2019 Sep 30.

Electrophysiology service, Montreal Heart Institute, Montreal, Quebec, Canada.

: Ventricular arrhythmias are often seen in association with structural heart disease. However, approximately a tenth of affected patients have apparently normal hearts, where such arrhythmias typically occur in young patients, are sometimes inherited and can occasionally lead to sudden cardiac death (SCD). Over the past two decades, increased understanding of the underlying pathophysiology resulted in improved targeted pharmacological therapy.: This article reviews current knowledge regarding drug therapy for inherited arrhythmia syndromes (Brugada, early repolarization, long QT and short QT syndromes, and catecholaminergic polymorphic ventricular tachycardia), and acquired arrhythmias (idiopathic ventricular fibrillation, short-coupled torsade de pointes, outflow tract ventricular tachycardia, idiopathic left, papillary muscle and annular ventricular tachycardias).: In inherited arrhythmia syndromes, appropriate clinical and genetic diagnoses followed by proper selection and dosing of antiarrhythmic drugs are of utmost importance to prevent SCD, most often without the need of implantable cardioverter-defibrillators. In acquired arrhythmias, appropriate pharmacotherapy in selected patients can also provide symptomatic relief and avoid the need for invasive therapy. Further research is needed to develop novel antiarrhythmic drugs or targeted therapy to increase efficacy and limit side effects.
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http://dx.doi.org/10.1080/14656566.2019.1669561DOI Listing
December 2019
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