Publications by authors named "Antoine H G Driessen"

45 Publications

Thoracoscopic surgical atrial fibrillation ablation in patients with an extremely enlarged left atrium.

J Interv Card Electrophysiol 2021 Sep 16. Epub 2021 Sep 16.

Department of Cardiology, Heart Center, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Purpose: Efficacy of pulmonary vein isolation (PVI) for atrial fibrillation (AF) decreases as left atrial (LA) volume increases. However, surgical AF ablation with unknown efficacy is being performed in patients with a giant LA (GLA). We determined efficacy of thoracoscopic AF ablation in patients with compared to without a GLA.

Methods: Patients underwent thoracoscopic PVI with additional left atrial ablations lines (in persistent AF) and were prospectively followed up. GLA was defined as LA volume index (LAVI) ≥ 50 ml/m. Follow-up was performed with ECGs and 24-h Holters every 3 months. After a 3-month blanking period, all antiarrhythmic drugs were discontinued. The primary outcome was freedom of any atrial tachyarrhythmia ≥ 30 s during 2 years of follow-up.

Results: At baseline, 68 (15.4%) patients had a GLA (LAVI: 56.7 [52.4-62.8] ml/m), while 374 (84.6%) had a smaller LA (LAVI: 34.8 [29.2-41.3] ml/m). GLA patients were older (61.9 ± 6.9 vs 59.4 ± 8.8 years, p = 0.02), more often diagnosed with persistent AF (76.5% vs 58.6%, p = 0.008). Sex was equally distributed (with approximately 25% females). GLA patients had more recurrences compared to non-GLA patients at 2-year follow-up (42.6% vs 57.2%, log rank p = 0.02). Freedom of AF was 69.0% in non-GLA paroxysmal AF patients compared to 43.8-49.3% in a combined group of GLA and/or persistent AF patients(log rank p < 0.001). Furthermore, freedom was 62.4% in non-GLA male patients, compared to 43.8-47.4 in a combined group of GLA and/or female sex(log rank p = 0.02).

Conclusion: Thoracoscopic AF ablation is an effective therapy in a substantial part of GLA patients. Thoracoscopic AF ablation may serve as a last resort treatment option in these patients.
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http://dx.doi.org/10.1007/s10840-021-01056-1DOI Listing
September 2021

Comparative evaluation of coronary disease burden: bicuspid valve disease is not atheroprotective.

Open Heart 2021 Sep;8(2)

Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands

Objective: Bicuspid aortic valve (BAV) has been associated with less atherosclerosis as compared with tricuspid aortic valve (TAV) patients. It, however, remains unclear whether this reflects the older age of TAV patients and/or accumulation of atherosclerotic risk factors or that the BAV phenotype is atheroprotective. Therefore, we compared the atherosclerotic disease burden of BAV and TAV patients, with that of the general (age-matched) population.

Methods: The prevalence of coronary artery disease (CAD) and CAD risk factors in BAV and TAV patients who underwent aortic valve surgery were compared with the Dutch general practitioners registry data. BAV (n=454) and TAV (n=1101) patients were divided into four groups: BAV with aortic valve stenosis (BAV-AoS), BAV with aortic valve regurgitation (BAV-AR), TAV with AoS (TAV-AoS) and TAV with AR (TAV-AR). The atherosclerotic disease burden of each group was compared with that of the corresponding age cohort for the general population.

Results: CAD risk factors hypertension and hypercholesterolaemia were more prevalent in the surgery groups than the age-matched general population (all p<0.001). All BAVs (BAV-AoS and BAV-AR) and TAV-AR had a similar incidence of CAD history as compared to the age-matched general populations (p=0.689, p=0.325 and p=0.617 respectively), whereas TAV-AoS had a higher incidence (21.6% versus 14.9% in the age-matched general population, p<0.001).

Conclusions: Stenotic TAV disease is part of the atherosclerotic disease spectrum, while regurgitant TAV and all BAVs are not. Although the prevalence of cardiovascular risk factors is higher in all BAV patients, the prevalence of CAD is similar to the general population.
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http://dx.doi.org/10.1136/openhrt-2021-001772DOI Listing
September 2021

Extracellular matrix remodeling precedes atrial fibrillation: Results of the PREDICT-AF trial.

Heart Rhythm 2021 Jul 29. Epub 2021 Jul 29.

Department of Clinical and Experimental Cardiology and Cardiothoracic Surgery, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. Electronic address:

Background: To which extent atrial remodeling occurs before atrial fibrillation (AF) is unknown.

Objective: The PREventive left atrial appenDage resection for the predICtion of fuTure Atrial Fibrillation (PREDICT-AF) study investigated such subclinical remodeling, which may be used for risk stratification and AF prevention.

Methods: Patients (N = 150) without a history of AF with a CHADS-VASc score of ≥2 at an increased risk of developing AF were included. The left atrial appendage was excised and blood samples were collected during elective cardiothoracic surgery for biomarker discovery. Participants were followed for 2 years with Holter monitoring to determine any atrial tachyarrhythmia after a 50-day blanking period.

Results: Eighteen patients (12%) developed incident AF, which was associated with increased tissue gene expression of collagen I (COL1A1), collagen III (COL3A1), and collagen VIII (COL8A2), tenascin-C (TNC), thrombospondin-2 (THBS2), and biglycan (BGN). Furthermore, the fibroblast activating endothelin-1 (EDN1) and sodium voltage-gated channel β subunit 2 (SCN2B) were associated with incident AF whereas the Kir2.1 channel (KCNJ2) tended to downregulate. The plasma levels of COL8A2 and TNC correlated with tissue expression and predicted incident AF. A gene panel including tissue KCNJ2, COL1A1, COL8A2, and EDN1 outperformed clinical prediction models in discriminating incident AF.

Conclusion: The PREDICT-AF study demonstrates that atrial remodeling occurs long before incident AF and implies future potential for early patient identification and therapies to prevent AF (ClinicalTrials.gov identifier NCT03130985).
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http://dx.doi.org/10.1016/j.hrthm.2021.07.059DOI Listing
July 2021

Extent of Coronary Artery Disease in Patients With Stenotic Bicuspid Versus Tricuspid Aortic Valves.

J Am Heart Assoc 2021 Jun 2;10(12):e020080. Epub 2021 Jun 2.

Department of Cardiothoracic Surgery Leiden University Medical Center the Netherlands.

Background Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, which is often complicated by aortic valve stenosis (AoS). In tricuspid aortic valve (TAV), AoS strongly associates with coronary artery disease (CAD) with common pathophysiological factors. Yet, it remains unclear whether AoS in patients with BAV is also associated with CAD. This study investigated the association between the aortic valve morphological features and the extent of CAD. Methods and Results A single-center study was performed, including all patients who underwent an aortic valve replacement attributable to AoS between 2006 and 2019. Coronary sclerosis was graded on preoperative coronary angiographies using the coronary artery greater even than scoring method, which divides the coronaries in 28 segments and scores nonobstructive (20%-49% sclerosis) and obstructive coronary sclerosis (>49% sclerosis) in each segment. Multivariate analyses were performed, controlling for age, sex, and CAD risk factors. A total of 1296 patients (931 TAV and 365 BAV) were included, resulting in 548 matched patients. Patients with TAV exhibited more CAD risk factors (odds ratio [OR], 2.66; 95% CI, 1.79-3.96; <0.001). Patients with BAV had lower coronary artery greater even than 20 (1.61±2.35 versus 3.60±2.79) and coronary artery greater even than 50 (1.24±2.43 versus 3.37±3.49) scores (<0.001), even after correcting for CAD risk factors (<0.001). Patients with TAV more often needed concomitant coronary revascularization (OR, 3.50; 95% CI, 2.42-5.06; <0.001). Conclusions Patients with BAV who are undergoing surgery for AoS carry a lower cardiovascular risk profile, correlating with less coronary sclerosis and a lower incidence of concomitant coronary revascularization compared with patients with TAV.
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http://dx.doi.org/10.1161/JAHA.120.020080DOI Listing
June 2021

Implementation of CT Coronary Angiography as an Alternative to Invasive Coronary Angiography in the Diagnostic Work-Up of Non-Coronary Cardiac Surgery, Cardiomyopathy, Heart Failure and Ventricular Arrhythmias.

J Clin Med 2021 May 28;10(11). Epub 2021 May 28.

Part of the Amsterdam Cardiovascular Sciences, Heart Centre, Amsterdam UMC, University of Amsterdam, 1105AZ Amsterdam, The Netherlands.

To assess the need for additional invasive coronary angiography (CAG) after initial computed tomography coronary angiography (CTCA) in patients awaiting non-coronary cardiac surgery and in patients with cardiomyopathy, heart failure or ventricular arrhythmias, and to determine differences between patients that were referred to initial CTCA or direct CAG, consecutive patients were included between August 2017 and January 2020 and categorized as those referred to initial CTCA (conform protocol), and to direct CAG (non-conform protocol). Out of a total of 415 patients, 78.8% (327 patients, mean age: 57.9 years, 67.3% male) were referred to initial CTCA, of whom 260 patients (79.5%) had no obstructive lesions (<50% DS). A total of 55 patients (16.8%) underwent additional CAG after initial CTCA, which showed coronary lesions of >50% DS in 21 patients (6.3% of 327). Eighty-eight patients (mean age: 66.0 years, 59.1% male) were directly referred to CAG (non-conform protocol). These patients were older and had more cardiovascular risk factors compared to patients that underwent initial CTCA (conform protocol), and coronary lesions of >50% DS were detected in 16 patients (17.2%). Revascularization procedures were infrequently performed in both groups: initial CTCA (3.0%), direct CAG (3.4%). The use of CTCA as a gatekeeper CAG in the diagnostic work-up of non-coronary cardiac surgery, cardiomyopathy, heart failure and ventricular arrhythmias is feasible, and only 17% of these patients required additional CAG after initial CTCA. Therefore, CTCA should be considered as the initial imaging modality to rule out CAD in these patients.
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http://dx.doi.org/10.3390/jcm10112374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199189PMC
May 2021

Patch-Clamp Recordings of Action Potentials From Human Atrial Myocytes: Optimization Through Dynamic Clamp.

Front Pharmacol 2021 12;12:649414. Epub 2021 Apr 12.

Department of Medical Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Consequently, novel therapies are being developed. Ultimately, the impact of compounds on the action potential (AP) needs to be tested in freshly isolated human atrial myocytes. However, the frequent depolarized state of these cells upon isolation seriously hampers reliable AP recordings. We assessed whether AP recordings from single human atrial myocytes could be improved by providing these cells with a proper inward rectifier K current (I), and consequently with a regular, non-depolarized resting membrane potential (RMP), through "dynamic clamp". Single myocytes were enzymatically isolated from left atrial appendage tissue obtained from patients with paroxysmal AF undergoing minimally invasive surgical ablation. APs were elicited at 1 Hz and measured using perforated patch-clamp methodology, injecting a synthetic I to generate a regular RMP. The injected I had strong or moderate rectification. For comparison, a regular RMP was forced through injection of a constant outward current. A wide variety of ion channel blockers was tested to assess their modulatory effects on AP characteristics. Without any current injection, RMPs ranged from -9.6 to -86.2 mV in 58 cells. In depolarized cells (RMP positive to -60 mV), RMP could be set at -80 mV using I or constant current injection and APs could be evoked upon stimulation. AP duration differed significantly between current injection methods ( < 0.05) and was shortest with constant current injection and longest with injection of I with strong rectification. With moderate rectification, AP duration at 90% repolarization (APD) was similar to myocytes with regular non-depolarized RMP, suggesting that a synthetic I with moderate rectification is the most appropriate for human atrial myocytes. Importantly, APs evoked using each injection method were still sensitive to all drugs tested (lidocaine, nifedipine, E-4031, low dose 4-aminopyridine, barium, and apamin), suggesting that the major ionic currents of the atrial cells remained functional. However, certain drug effects were quantitatively dependent on the current injection approach used. Injection of a synthetic I with moderate rectification facilitates detailed AP measurements in human atrial myocytes. Therefore, dynamic clamp represents a promising tool for testing novel antiarrhythmic drugs.
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http://dx.doi.org/10.3389/fphar.2021.649414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072333PMC
April 2021

Neutrophil degranulation interconnects over-represented biological processes in atrial fibrillation.

Sci Rep 2021 Feb 3;11(1):2972. Epub 2021 Feb 3.

Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Heart Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Despite our expanding knowledge about the mechanism underlying atrial fibrillation (AF), the interplay between the biological events underlying AF remains incompletely understood. This study aimed to identify the functionally enriched gene-sets in AF and capture their interconnection via pivotal factors, that may drive or be driven by AF. Global abundance of the proteins in the left atrium of AF patients compared to control patients (n = 3/group), and the functionally enriched biological processes in AF were determined by mass-spectrometry and gene set enrichment analysis, respectively. The data were validated in an independent cohort (n = 19-20/group). In AF, the gene-sets of innate immune system, metabolic process, cellular component disassembly and ion homeostasis were up-regulated, while the gene-set of ciliogenesis was down-regulated. The innate immune system was over-represented by neutrophil degranulation, the components of which were extensively shared by other gene-sets altered in AF. In the independent cohort, an activated form of neutrophils was more present in the left atrium of AF patients with the increased gene expression of neutrophil granules. MYH10, required for ciliogenesis, was decreased in the atrial fibroblasts of AF patients. We report the increased neutrophil degranulation appears to play a pivotal role, and affects multiple biological processes altered in AF.
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http://dx.doi.org/10.1038/s41598-021-82533-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859227PMC
February 2021

Pre-PCI versus immediate post-PCI Impella initiation in acute myocardial infarction complicated by cardiogenic shock.

PLoS One 2020 20;15(7):e0235762. Epub 2020 Jul 20.

Department of Cardiology, Amsterdam University Medical Center, Amsterdam, The Netherlands.

Background: In selected patients with an acute myocardial infarction (AMI) complicated by Cardiogenic shock (CS), mechanical circulatory support with Impella may be beneficial, although conclusive evidence is still lacking. Nevertheless, it has been suggested that Impella initiation prior to primary PCI might improve survival.

Objective: To investigate the effect pre-PCI versus immediate post-PCI Impella initiation on short term mortality.

Methods: A prospective, single center, observational study, was performed including all patients with STEMI complicated by CS, treated with primary PCI and Impella. Thirty day mortality was compared between patients with Impella initiation pre-PCI and immediately post-PCI.

Results: A total of 88 patients were included. In the pre-PCI group (n = 21), admission heart rate was lower (84 versus 94 bpm, p = 0.04) and no IABP was implanted before Impella initiation, versus 17.9% in post-PCI group (n = 67), p = 0.04. Total 30-day all-cause mortality was 58%, and was lower in pre-PCI group, 47.6% versus 61.2% in the post-PCI group, however not statistically significant (HR 0.7, 95% CI 0.3-1.3, p = 0.21). Thirty-day cardiac mortality was significantly lower in the pre-PCI group, 19% versus 44.7% in the post-PCI group (HR 0.3, 95% CI 0.09-0.96, p = 0.042).

Conclusion: Pre-PCI Impella initiation in AMICS patients was not associated with a statistically significant difference in 30-day all-cause mortality, compared to post-PCI Impella initiation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235762PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371192PMC
September 2020

Clinical course of sinus node dysfunction after thoracoscopic surgery for atrial fibrillation-analysis of the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT) study.

J Interv Card Electrophysiol 2021 Mar 14;60(2):185-193. Epub 2020 Mar 14.

Department of Cardiology, Heart Center, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Purpose: Sinus node dysfunction (SND) may complicate thoracoscopic surgical atrial fibrillation (AF) ablation. Identifying patients at risk is important, as SND may require temporary or permanent pacing. To determine the incidence of postoperative SND and duration of symptoms in patients who underwent thoracoscopic surgical ablation.

Methods: Patients with paroxysmal or persistent AF included in the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT) study underwent pulmonary vein isolation and additional left atrial ablations on indication. Patients were randomized to ganglion plexus ablation or control. SND was defined as symptomatic or asymptomatic junctional rhythm exceeding sinus rate within 30 days postoperatively. The SND risk was assessed by using a univariable logistic regression model. The rate of pacemaker implantation was determined.

Results: The AFACT study included 240 patients. SND developed in 17 (7.1%) patients, not affected by randomized treatment, p = 0.18. SND patients more often had persistent AF (88.2%) than patients without SND (57.4%), p = 0.01. After univariable testing, persistent AF (OR 5.57 CI 1.52-35.90, p = 0.02) and additional left atrial ablations (OR 12.10 CI 2.40-220.20, p = 0.02) were associated with postoperative SND. Six (35.3%) patients needed temporary pacing for 1-7 days; permanent pacemakers (PMs) were implanted for SND in five (29.4%) patients.

Conclusion: Additional left atrial ablations strongly increase the SND risk. The majority of SND was temporary, and sinus rhythm resolved within days, which indicates that a conservative approach with regard to pacemaker implantation should be considered.
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http://dx.doi.org/10.1007/s10840-020-00722-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925456PMC
March 2021

Absence of Functional Na1.8 Channels in Non-diseased Atrial and Ventricular Cardiomyocytes.

Cardiovasc Drugs Ther 2019 12;33(6):649-660

Department of Experimental Cardiology, Amsterdam UMC, Meibergdreef 15, Amsterdam, 1105 AZ, The Netherlands.

Purpose: Several studies have indicated a potential role for SCN10A/Na1.8 in modulating cardiac electrophysiology and arrhythmia susceptibility. However, by which mechanism SCN10A/Na1.8 impacts on cardiac electrical function is still a matter of debate. To address this, we here investigated the functional relevance of Na1.8 in atrial and ventricular cardiomyocytes (CMs), focusing on the contribution of Na1.8 to the peak and late sodium current (I) under normal conditions in different species.

Methods: The effects of the Na1.8 blocker A-803467 were investigated through patch-clamp analysis in freshly isolated rabbit left ventricular CMs, human left atrial CMs and human-induced pluripotent stem cell-derived CMs (hiPSC-CMs).

Results: A-803467 treatment caused a slight shortening of the action potential duration (APD) in rabbit CMs and hiPSC-CMs, while it had no effect on APD in human atrial cells. Resting membrane potential, action potential (AP) amplitude, and AP upstroke velocity were unaffected by A-803467 application. Similarly, I density was unchanged after exposure to A-803467 and Na1.8-based late I was undetectable in all cell types analysed. Finally, low to absent expression levels of SCN10A were observed in human atrial tissue, rabbit ventricular tissue and hiPSC-CMs.

Conclusion: We here demonstrate the absence of functional Na1.8 channels in non-diseased atrial and ventricular CMs. Hence, the association of SCN10A variants with cardiac electrophysiology observed in, e.g. genome wide association studies, is likely the result of indirect effects on SCN5A expression and/or Na1.8 activity in cell types other than CMs.
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http://dx.doi.org/10.1007/s10557-019-06925-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994555PMC
December 2019

PREventive left atrial appenDage resection for the predICtion of fuTure atrial fibrillation: design of the PREDICT AF study.

J Cardiovasc Med (Hagerstown) 2019 Nov;20(11):752-761

Department of Cardiology and Experimental Cardiology, Heart Center, Amsterdam UMC, University of Amsterdam, Amsterdam.

Background: Atrial fibrillation is the most common cardiac arrhythmia, posing a heavy burden on patients' wellbeing and healthcare budgets. Patients undergoing cardiac surgery are at risk of developing postoperative atrial fibrillation (POAF), new-onset atrial fibrillation and subsequent atrial fibrillation-related complications, including stroke. Sufficient clinical identification of patients at risk fails while the pathological substrate changes that precede atrial fibrillation remain unknown. Here, we describe the PREDICT AF study design, which will be the first study to associate tissue pathophysiology and blood biomarkers with clinical profiling and follow-up of cardiothoracic surgery patients for the prediction of future atrial fibrillation.

Methods: PREDICT AF will include 150 patients without atrial fibrillation and a CHA2DS2-VASc score of at least 2 undergoing cardiac surgery. The left atrial appendage will be excised during surgery and blood samples will be collected before surgery and at 6 and 12 months' follow-up. Tissue and blood analysis will be used for the discovery of biomarkers including microRNAs and protein biomarkers. The primary study endpoint is atrial fibrillation, which will be objectified by 24 h Holters and ECGs after 30 days for POAF and after 6, 12 and 24 months for new-onset atrial fibrillation. Secondary endpoints include the dynamic changes of blood biomarkers over time and other atrial arrhythmias. PREDICT AF participants may benefit from extensive postoperative care with clinical phenotyping, rhythm monitoring and primary prevention of stroke.

Conclusion: We here describe the PREDICT AF trial design, which will enable the discovery of biomarkers that truly predict POAF and new-onset atrial fibrillation by combining tissue and plasma-derived biomarkers with comprehensive clinical follow-up data.

Trial Registration: Retrospectively registered NCT03130985 27 April 2017.
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http://dx.doi.org/10.2459/JCM.0000000000000868DOI Listing
November 2019

Acetylcholine Delays Atrial Activation to Facilitate Atrial Fibrillation.

Front Physiol 2019 4;10:1105. Epub 2019 Sep 4.

Department of Cardiology, Academic Medical Center, Amsterdam, Netherlands.

Background: Acetylcholine (ACh) shortens action potential duration (APD) in human atria. APD shortening facilitates atrial fibrillation (AF) by reducing the wavelength for reentry. However, the influence of ACh on electrical conduction in human atria and its contribution to AF are unclear, particularly when combined with impaired conduction from interstitial fibrosis.

Objective: To investigate the effect of ACh on human atrial conduction and its role in AF with computational, experimental, and clinical approaches.

Methods: S1S2 pacing (S1 = 600 ms and S2 = variable cycle lengths) was applied to the following human AF computer models: a left atrial appendage (LAA) myocyte to quantify the effects of ACh on APD, maximum upstroke velocity (V ), and resting membrane potential (RMP); a monolayer of LAA myocytes to quantify the effects of ACh on conduction; and 3) an intact left atrium (LA) to determine the effects of ACh on arrhythmogenicity. Heterogeneous ACh and interstitial fibrosis were applied to the monolayer and LA models. To corroborate the simulations, APD and RMP from isolated human atrial myocytes were recorded before and after 0.1 μM ACh. At the tissue level, LAAs from AF patients were optically mapped using Di-4-ANEPPS. The difference in total activation time (AT) was determined between AT initially recorded with S1 pacing, and AT recorded during subsequent S1 pacing without ( = 6) or with ( = 7) 100 μM ACh.

Results: In LAA myocyte simulations, S1 pacing with 0.1 μM ACh shortened APD by 41 ms, hyperpolarized RMP by 7 mV, and increased V by 27 mV/ms. In human atrial myocytes, 0.1 μM ACh shortened APD by 48 ms, hyperpolarized RMP by 3 mV, and increased V by 6 mV/ms. In LAA monolayer simulations, S1 pacing with ACh hyperpolarized RMP to delay total AT by 32 ms without and 35 ms with fibrosis. This led to unidirectional conduction block and sustained reentry in fibrotic LA with heterogeneous ACh during S2 pacing. In AF patient LAAs, S1 pacing with ACh increased total AT from 39.3 ± 26 ms to 71.4 ± 31.2 ms ( = 0.036) compared to no change without ACh (56.7 ± 29.3 ms to 50.0 ± 21.9 ms, = 0.140).

Conclusion: In fibrotic atria with heterogeneous parasympathetic activation, ACh facilitates AF by shortening APD and slowing conduction to promote unidirectional conduction block and reentry.
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http://dx.doi.org/10.3389/fphys.2019.01105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737394PMC
September 2019

Additional Ganglion Plexus Ablation During Thoracoscopic Surgical Ablation of Advanced Atrial Fibrillation: Intermediate Follow-Up of the AFACT Study.

JACC Clin Electrophysiol 2019 03 28;5(3):343-353. Epub 2018 Nov 28.

Department of Cardiology, Heart Center, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Electronic address:

Objectives: The authors report the 2-year follow-up results of the AFACT (Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery) study.

Background: The AFACT study randomized patients with advanced atrial fibrillation (AF) to thoracoscopic AF ablation with or without additional ganglion plexus (GP) ablation. At 1 year, there was no difference in AF freedom between the groups, but autonomic modification may exert beneficial effects during longer follow-up.

Methods: Patients underwent thoracoscopic pulmonary vein isolation, with additional left atrial lines in persistent AF patients, and were randomized 1:1 to ablation of the 4 major GP and Marshall ligament or no GP ablation (control). Patients were followed every 3 months up to 18 months and at 24 months. After an initial 3-month blanking period, all antiarrhythmic drugs were discontinued.

Results: The authors randomized 240 patients (age 59 ± 8 years, 73% men, 68% enlarged left atrium, 60% persistent AF), of whom 228 patients (95%) completed follow-up. Freedom of any atrial tachyarrhythmia did not differ significantly between the GP group (55.6%) and control group (56.1%) (p = 0.91), with no difference in paroxysmal (p = 0.60) or persistent AF patients (p = 0.88). Documented AF recurrences were similar between treatment arms: 11.8% (GP) versus 11.0% (control) had >3 recurrences/year (p = 0.82). More persistent AF patients (17.0%) than paroxysmal (3.2%) had >3 recurrences per year (p < 0.01). Despite this, 78% of patients were off antiarrhythmic drugs after 2 years. No procedural-related complications occurred in the second year.

Conclusions: Additional GP ablation during thoracoscopic surgery for advanced AF does not affect freedom of AF recurrence. As GP ablation is associated with more major procedural complications, it should not routinely be performed. (Atrial Fibrillation Ablation and Autonomic Modulation via Thorascopic Surgery [AFACT]; NCT01091389).
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http://dx.doi.org/10.1016/j.jacep.2018.10.008DOI Listing
March 2019

Early initiation of extracorporeal life support in refractory out-of-hospital cardiac arrest: Design and rationale of the INCEPTION trial.

Am Heart J 2019 04 14;210:58-68. Epub 2018 Dec 14.

Department of Intensive Care, Maastricht University Medical Center, Maastricht, The Netherlands; NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands; Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.

Return of spontaneous circulation occurs in less than 10% of patients with cardiac arrest undergoing cardiopulmonary resuscitation (CPR) for more than 15 minutes. Studies suggest that extracorporeal life support during cardiopulmonary resuscitation (ECPR) improves survival rate in these patients. These studies, however, are hampered by their non-randomized, observational design and are mostly single-center. A multicenter, randomized controlled trial is urgently warranted to evaluate the effectiveness of ECPR.

Hypothesis: We hypothesize that early initiation of ECPR in refractory out-of-hospital cardiac arrest (OHCA) improves the survival rate with favorable neurological status.

Study Design: The INCEPTION trial is an investigator-initiated, prospective, multicenter trial that will randomly allocate 110 patients to either continued CPR or ECPR in a 1:1 ratio. Patients eligible for inclusion are adults (≤ 70 years) with witnessed OHCA presenting with an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT), who received bystander basic life support and who fail to achieve sustained return of spontaneous circulation within 15 minutes of cardiopulmonary resuscitation by emergency medical services. The primary endpoint of the study is 30-day survival rate with favorable neurological status, defined as 1 or 2 on the Cerebral Performance Category score. The secondary endpoints include 3, 6 and 12-month survival rate with favorable neurological status and the cost-effectiveness of ECPR compared to CCPR.

Summary: The INCEPTION trial aims to determine the clinical benefit for the use of ECPR in patients with refractory OHCA presenting with VF/VT. Additionally, the feasibility and cost-effectiveness of ECPR will be evaluated.
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http://dx.doi.org/10.1016/j.ahj.2018.12.008DOI Listing
April 2019

Persistent atrial fibrillation: A systematic review and meta-analysis of invasive strategies.

Int J Cardiol 2019 Mar 29;278:137-143. Epub 2018 Nov 29.

Amsterdam UMC, University of Amsterdam, Department of Cardiology, Heart Center, Meibergdreef 9, Amsterdam, the Netherlands. Electronic address:

Background: Persistent atrial fibrillation (AF) is associated with higher stroke and mortality risk than paroxysmal AF (pAF). Outcomes of catheter or surgical ablation are worse in patients with persistent AF than in pAF, and the optimal invasive rhythm control strategy has not been established.

Purpose: We provide a contemporary systematic overview on efficacy and safety of catheter and minimally-invasive surgical ablation for persistent AF.

Methods: We systematically searched EMBASE, MEDLINE and CENTRAL from inception to July 2018 for randomized trials on surgical and catheter ablation, and included all study arms on persistent AF. Outcome was AF freedom after ≥12 months follow-up without AAD use. Random effects models were used to calculate proportions with 95%-confidence intervals. Safety consisted of adverse events during treatment and follow-up.

Results: We included 6 studies on minimally-invasive surgical ablation and 56 on catheter ablation, involving 7624 patients with persistent AF. AF Freedom at 12 months was 69% (95%CI 64-74%) after surgical and 51% (95%CI 46-56%) after catheter ablation. More severe procedural adverse events occurred with surgery than with catheter ablation.

Conclusions: In persistent AF patients, minimally-invasive surgical ablation is associated with more procedural complications, but higher AF freedom. As adverse events after surgical ablation appear more severe than in catheter ablation, a patient-tailored therapy choice is warranted.
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http://dx.doi.org/10.1016/j.ijcard.2018.11.127DOI Listing
March 2019

Neurokinin-3 receptor activation selectively prolongs atrial refractoriness by inhibition of a background K channel.

Nat Commun 2018 10 19;9(1):4357. Epub 2018 Oct 19.

Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

The cardiac autonomic nervous system (ANS) controls normal atrial electrical function. The cardiac ANS produces various neuropeptides, among which the neurokinins, whose actions on atrial electrophysiology are largely unknown. We here demonstrate that the neurokinin substance-P (Sub-P) activates a neurokinin-3 receptor (NK-3R) in rabbit, prolonging action potential (AP) duration through inhibition of a background potassium current. In contrast, ventricular AP duration was unaffected by NK-3R activation. NK-3R stimulation lengthened atrial repolarization in intact rabbit hearts and consequently suppressed arrhythmia duration and occurrence in a rabbit isolated heart model of atrial fibrillation (AF). In human atrial appendages, the phenomenon of NK-3R mediated lengthening of atrial repolarization was also observed. Our findings thus uncover a pathway to selectively modulate atrial AP duration by activation of a hitherto unidentified neurokinin-3 receptor in the membrane of atrial myocytes. NK-3R stimulation may therefore represent an anti-arrhythmic concept to suppress re-entry-based atrial tachyarrhythmias, including AF.
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http://dx.doi.org/10.1038/s41467-018-06530-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195571PMC
October 2018

Guideline-defined futility or patient-reported outcomes to assess treatment success after TAVI: what to use? Results from a prospective cohort study with long-term follow-up.

Open Heart 2018;5(2):e000879. Epub 2018 Sep 23.

Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Objective: Transcatheter aortic valve implantation (TAVI) provides a significant symptom relief and mortality reduction in most patients; however, a substantial group of patients does not experience the same beneficial results according to physician-determined outcomes.

Methods: Single-centre prospective design; the population comprises all consecutive patients undergoing TAVI in 2012-2017. TAVI futility was defined as the combined endpoint of either no symptomatic improvement or mortality at 1 year. We actively gathered telephone follow-up using a predefined questionnaire.

Results: Guideline defined TAVI futility was present in 212/741 patients. Multivariate regression showed lower albumin and non-transfemoral approach to be predictive for futility. In addition to these, chronic obstructive pulmonary disease, lower estimated glomerular filtration rate, atrial fibrillation, low-flow-low-gradient aortic stenosis and lower Body Mass Index were predictive for 1-year mortality. Patients who showed symptomatic benefit estimated the percentage in which their symptoms were remedied higher than patients who did not (80% vs 60%, p<0.001). Guideline-defined TAVI futility occurs frequently, contrasting with patient-reported outcome measures (PROMs). The vast majority in both groups would again choose for TAVI treatment.

Conclusion: Lower albumin and non-transfemoral access route were predictors for guideline-defined TAVI futility, defined as mortality within 1 year or no objective symptomatic improvement in New York Heart Association class. Futility according to this definition occurred frequently in this study, contrasting with much more positive PROMs. The majority of patients would undergo a TAVI again, underlining the patients' experienced value of TAVI and putting the definition of TAVI futility further on debate. In the near future, less-strict criteria for TAVI futility, that is, using a shorter warranted life expectancy and incorporating patients' perceived outcomes, should be used.
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http://dx.doi.org/10.1136/openhrt-2018-000879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157566PMC
February 2021

Procedural Outcome and Midterm Survival of Lower Risk Transfemoral Transcatheter Aortic Valve Implantation Patients Treated With the SAPIEN XT or SAPIEN 3 Device.

Am J Cardiol 2018 04 11;121(7):856-861. Epub 2018 Jan 11.

Heart Centre, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

Over the years increasing experience and technical device improvements in transcatheter aortic valve implantation (TAVI) have led to treatment of patients with lower surgical risks. Specifically for this population, device performance and longer term outcome are of great importance. In this single center, we performed a retrospective analysis of 515 consecutive patients with low- to intermediate surgical risk (STS-PROM ≤8), who underwent transfemoral TAVI between January 2009 and February 2017 with the SXT and ES3 prostheses, and we assessed procedural outcome and procedural and 3-year survival. Mean age (82 years in both groups, p = 0.344) and STS-PROM risk score (3.862 vs 3.992, p = 0.154) did not differ between the ES3 and SXT group. ES3-treated patients showed favorable procedural outcomes, with significantly higher device success (90% vs 73%, p <0.0001) and less paravalvular leakage (7% vs 13%, p <0.0001). Procedural mortality (0.87% vs 1.45%, p = 0.245) and the very low rate of permanent pacemaker implantations (7.4% vs 6.1%, p = 0.234) did not differ significantly. Three-year survival was 87% in the ES3 vs 80% in the SXT group (log-rank p = 0.385). In conclusion, we showed excellent survival and procedural outcomes in patients receiving a transfemoral TAVI with either the SAPIEN 3 or the SAPIEN XT device. The newer SAPIEN 3 even outperforms the SAPIEN XT in terms of less major bleeding complications, substantially higher device success rates, and less paravalvular leakage, with the permanent pacemaker implantation rate being very low in both groups. Survival curves show a nonsignificant trend toward better midterm survival in the ES3 group.
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http://dx.doi.org/10.1016/j.amjcard.2017.12.024DOI Listing
April 2018

Quality of life improves after thoracoscopic surgical ablation of advanced atrial fibrillation: Results of the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT) study.

J Thorac Cardiovasc Surg 2018 03 27;155(3):972-980. Epub 2017 Sep 27.

Department of Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address:

Objective: We evaluated health-related quality of life at 12 months after thoracoscopic surgical ablation in patients enrolled in the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery study. The Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery study assessed the efficacy and safety of ganglion plexus ablation in patients with symptomatic advanced atrial fibrillation undergoing thoracoscopic surgical ablation.

Methods: Patients (n = 240) underwent thoracoscopic pulmonary vein isolation with additional ablation lines in patients with persistent atrial fibrillation. Subjects were randomized to additional ganglion plexus ablation or control. Short Form 36 quality of life questionnaires were collected at baseline and at 6 and 12 months of follow-up.

Results: A total of 201 patients were eligible for quality of life analysis (age 59 ± 8 years, 72% were men, 68% had an enlarged left atrium, 57% had persistent atrial fibrillation). Patients improved in physical and mental health at 6 months (both P < .01) and 12 months (both P < .01) relative to baseline, with no difference between the ganglion plexus (n = 101) and control (n = 100) groups. Short Form 36 subscores in patients with 1 or no atrial fibrillation recurrences were similar to those in the general Dutch population after 12 months. Patients with multiple atrial fibrillation recurrences (30%) improved in mental (P < .01), but not physical health, and 6 of 8 Short Form 36 subscales remained below those of the general Dutch population. Patients with irreversible, but not with reversible procedural complications had persistently diminished quality of life scores at 12 months.

Conclusions: Thoracoscopic surgery for advanced atrial fibrillation results in improvement in quality of life, regardless of additional ganglion plexus ablation. Quality of life in patients with no or 1 atrial fibrillation recurrence increased to the level of the general Dutch population, whereas in patients with multiple atrial fibrillation recurrences quality of life remained lower. Irreversible but not reversible procedural complications were associated with persistently lower quality of life.
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http://dx.doi.org/10.1016/j.jtcvs.2017.09.093DOI Listing
March 2018

The change in circulating galectin-3 predicts absence of atrial fibrillation after thoracoscopic surgical ablation.

Europace 2018 05;20(5):764-771

Department of Cardiology, Experimental Cardiology and Cardiothoracic Surgery, Heart Center, Academic Medical Center, Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands.

Aims: Galectin-3 (Gal-3) is an important mediator of cardiac fibrosis, particularly in heart failure. Increased Gal-3 concentration (Gal-3), associated with increased risk of developing atrial fibrillation (AF), may reflect atrial fibrotic remodelling underlying AF progression. We aimed to investigate whether the change in serum Gal-3 reflects alterations of the arrhythmogenic atrial substrate following thoracoscopic AF surgery, and predicts absence of AF.

Methods And Results: Consecutive patients undergoing thoracoscopic AF surgery were included. Left atrial appendages (LAAs) and serum were collected during surgery and serum again 6 months thereafter. Gal-3 was determined in tissue and serum. Interstitial collagen in the LAA was quantified using Picrosirius red staining. Ninety-eight patients (76% male, mean age 60 ± 9 years) underwent thoracoscopic surgery for advanced AF. Patients with increased Gal-3 after ablation compared to baseline had a higher recurrence rate compared to patients with decreased or unchanged Gal-3 (HR 2.91, P = 0.014). These patients more frequently had persistent AF, longer AF duration and thick atrial collagen strands (P = 0.049). At baseline, Gal-3 was similar between patients with and without AF recurrence: 14.8 ± 3.9 µg/L vs. 13.7 ± 3.7 µg/L, respectively in serum (P = 0.16); 94.5 ± 19.4 µg/L vs. 93.3 ± 30.8µg/L, respectively in atrial myocardium (P = 0.83). There was no correlation between serum Gal-3 and left atrial Gal-3 (P = 0.20), nor between serum Gal-3 and the percentage of fibrosis in LAA (P = 0.18).

Conclusion: The change of circulating Gal-3, rather than its baseline value, predicts AF recurrence after thoracoscopic ablation. Patients in whom Gal-3 increases after ablation have a high recurrence rate reflecting ongoing profibrotic signalling, irrespective of arrhythmia continuation.
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http://dx.doi.org/10.1093/europace/eux090DOI Listing
May 2018

Assessment of the Extravascular Implantable Defibrillator: Feasibility of Substernal Ventricular Pacing.

J Cardiovasc Electrophysiol 2017 Jun 4;28(6):674-676. Epub 2017 Apr 4.

Department of Clinical and Experimental Cardiology, Amsterdam, the Netherlands.

Introduction: The objective of this study was to assess feasibility of ventricular pacing and thresholds from within the substernal space to examine a new extravascular ICD configuration with pacing capabilities.

Methods: In patients undergoing midline sternotomy, a duodecapolar diagnostic pacing catheter was positioned in the substernal space anterior to the pericardium, and a cutaneous patch in left lateral position. Different unipolar and bipolar pacing configurations were assessed. Strength-duration curves were performed to identify the optimal output, starting at 25 mA with a pulse width of 10 milliseconds.

Results: Eight patients with mean age 69 ± 9 years were included. In 5, ventricular capture was achieved in ≥1 configuration. The mean bipolar pacing thresholds at PW 10, 5, 3, 1 milliseconds were 12.4 ± 3.7 mA (5 patients), 13.3 ± 5.8 mA (3 patients), 18.3 ± 5.7 mA (3 patients), and 25 ± 0 mA (2 patients), respectively. The 60-mm electrode spacing was the most successful bipolar configuration. Unipolar pacing was successful in 3 out of 4 patients with mean thresholds of 10 ± 0 mA at 10 milliseconds (3 patients), 15 ± 0 mA at 5 milliseconds (3 patients), 16.7 ± 2.9 mA at 3 milliseconds (3 patients), and 20 ± 7.1 mA at 1 milliseconds (2 patients).

Conclusion: Ventricular pacing from the substernal space in patients with midline sternotomy is feasible. Closed sternum studies are needed to determine pacing thresholds more accurately.
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http://dx.doi.org/10.1111/jce.13195DOI Listing
June 2017

To the Editor- Ganglionic plexus ablation in advanced atrial fibrillation.

Heart Rhythm 2016 12 26;13(12):e331. Epub 2016 Aug 26.

Department of Cardiothoracic Surgery Academic Medical Center Amsterdam, The Netherlands.

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http://dx.doi.org/10.1016/j.hrthm.2016.08.039DOI Listing
December 2016

Extracorporeal life support during cardiac arrest and cardiogenic shock: a systematic review and meta-analysis.

Intensive Care Med 2016 Dec 19;42(12):1922-1934. Epub 2016 Sep 19.

AMC Heart Center, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Purpose: Veno-arterial extracorporeal life support (ECLS) is increasingly used in patients during cardiac arrest and cardiogenic shock, to support both cardiac and pulmonary function. We performed a systematic review and meta-analysis of cohort studies comparing mortality in patients treated with and without ECLS support in the setting of refractory cardiac arrest and cardiogenic shock complicating acute myocardial infarction.

Methods: We systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed updated to December 2015. Thirteen studies were included of which nine included cardiac arrest patients (n = 3098) and four included patients with cardiogenic shock after acute myocardial infarction (n = 235). Data were pooled by a Mantel-Haenzel random effects model and heterogeneity was examined by the I statistic.

Results: In cardiac arrest, the use of ECLS was associated with an absolute increase of 30 days survival of 13 % compared with patients in which ECLS was not used [95 % CI 6-20 %; p < 0.001; number needed to treat (NNT) 7.7] and a higher rate of favourable neurological outcome at 30 days (absolute risk difference 14 %; 95 % CI 7-20 %; p < 0.0001; NNT 7.1). Propensity matched analysis, including 5 studies and 438 patients (219 in both groups), showed similar results. In cardiogenic shock, ECLS showed a 33 % higher 30-day survival compared with IABP (95 % CI, 14-52 %; p < 0.001; NNT 13) but no difference when compared with TandemHeart/Impella (-3 %; 95 % CI -21 to 14 %; p = 0.70; NNH 33).

Conclusions: In cardiac arrest, the use of ECLS was associated with an increased survival rate as well as an increase in favourable neurological outcome. In the setting of cardiogenic shock there was an increased survival with ECLS compared with IABP.
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http://dx.doi.org/10.1007/s00134-016-4536-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106498PMC
December 2016

Ganglion Plexus Ablation in Advanced Atrial Fibrillation: The AFACT Study.

J Am Coll Cardiol 2016 09;68(11):1155-1165

Department of Cardiology, Heart Center, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands. Electronic address:

Background: Patients with long duration of atrial fibrillation (AF), enlarged atria, or failed catheter ablation have advanced AF and may require more extensive treatment than pulmonary vein isolation.

Objectives: The aim of this study was to investigate the efficacy and safety of additional ganglion plexus (GP) ablation in patients undergoing thoracoscopic AF surgery.

Methods: Patients with paroxysmal AF underwent pulmonary vein isolation. Patients with persistent AF also received additional lines (Dallas lesion set). Patients were randomized 1:1 to additional epicardial ablation of the 4 major GPs and Marshall's ligament (GP group) or no extra ablation (control) and followed every 3 months for 1 year. After a 3-month blanking period, all antiarrhythmic drugs were discontinued.

Results: Two hundred forty patients with a mean AF duration of 5.7 ± 5.1 years (59% persistent) were included. Mean procedure times were 185 ± 54 min and 168 ± 54 min (p = 0.015) in the GP (n = 117) and control groups (n = 123), respectively. GP ablation abated 100% of evoked vagal responses; these responses remained in 87% of control subjects. Major bleeding occurred in 9 patients (all in the GP group; p < 0.001); 8 patients were managed thoracoscopically, and 1 underwent sternotomy. Sinus node dysfunction occurred in 12 patients in the GP group and 4 control subjects (p = 0.038), and 6 pacemakers were implanted (all in the GP group; p = 0.013). After 1 year, 4 patients had died (all in the GP group, not procedure related; p = 0.055), and 9 were lost to follow-up. Freedom from AF recurrence in the GP and control groups was not statistically different whether patients had paroxysmal or persistent AF. At 1 year, 82% of patients were not taking antiarrhythmic drugs.

Conclusions: GP ablation during thoracoscopic surgery for advanced AF has no detectable effect on AF recurrence but causes more major adverse events, major bleeding, sinus node dysfunction, and pacemaker implantation. (Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery [AFACT]; NCT01091389).
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http://dx.doi.org/10.1016/j.jacc.2016.06.036DOI Listing
September 2016

Surgical Management of Implantation-Related Complications of the Subcutaneous Implantable Cardioverter-Defibrillator.

JACC Clin Electrophysiol 2016 Feb 17;2(1):89-96. Epub 2015 Oct 17.

Department of Clinical and Experimental Cardiology, Heart Center, Amsterdam Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Objectives: This study assessed outcomes in patients in whom subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy was continued after implantation-related complications, in order to avoid conversion to transvenous ICD therapy.

Background: Patients at risk for sudden cardiac death benefit from ICD therapy, despite a significant risk for complications. S-ICD has a similar complication rate as transvenous ICD therapy, but the absence of transvenous leads may hold long-term benefits, especially in young ICD patients.

Methods: In the largest single-center cohort available to date, S-ICD patients implanted between 2009 and 2015 were included.

Results: There were 123 patients at a median age of 40 years. During a median follow-up of 2 years, 10 patients (9.4%) suffered implant-related complications. There were 5 infections, 3 erosions, and 2 implant failures for which 21 surgical procedures were needed. In 9 of 10 patients, S-ICD therapy could be continued after intervention. In 6 patients, the period between extraction and reimplantation of the S-ICD system was bridged with a wearable cardioverter-defibrillator (WCD). The pulse generator was reimplanted at the original site in 5 patients and in 3 underneath the serratus anterior muscle. One patient was not reimplanted following extraction due to recurrent infections. Conversion to a transvenous ICD was not needed in any patient.

Conclusions: In most patients with a complication, S-ICD therapy could be continued after intervention, avoiding the need to convert to a transvenous system. Bridging to recovery with a WCD and submuscular implantation of the pulse generator are effective treatment strategies to manage S-ICD complications.
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http://dx.doi.org/10.1016/j.jacep.2015.09.011DOI Listing
February 2016

Treatment of Atrial and Ventricular Arrhythmias Through Autonomic Modulation.

JACC Clin Electrophysiol 2015 Dec 24;1(6):496-508. Epub 2015 Oct 24.

Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, the Netherlands. Electronic address:

This paper reviews the contribution of autonomic nervous system (ANS) modulation in the treatment of arrhythmias. Both the atria and ventricles are innervated by an extensive network of nerve fibers of parasympathetic and sympathetic origin. Both the parasympathetic and sympathetic nervous system exert arrhythmogenic electrophysiological effects on atrial and pulmonary vein myocardium, while in the ventricle the sympathetic nervous system plays a more dominant role in arrhythmogenesis. Identification of ANS activity is possible with nuclear imaging. This technique may provide further insight in mechanisms and treatment targets. Additionally, the myocardial effects of the intrinsic ANS can be identified through stimulation of the ganglionic plexuses. These can be ablated for the treatment of atrial fibrillation. New (non-) invasive treatment options targeting the extrinsic cardiac ANS, such as low-level tragus stimulation and renal denervation, provide interesting future treatment possibilities both for atrial fibrillation and ventricular arrhythmias. However, the first randomized trials have yet to be performed. Future clinical studies on modifying the ANS may not only improve the outcome of ablation therapy but may also advance our understanding of the manner in which the ANS interacts with the myocardium to modify arrhythmogenic triggers and substrate.
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http://dx.doi.org/10.1016/j.jacep.2015.09.013DOI Listing
December 2015

ST-Segment Elevation and Fractionated Electrograms in Brugada Syndrome Patients Arise From the Same Structurally Abnormal Subepicardial RVOT Area but Have a Different Mechanism.

Circ Arrhythm Electrophysiol 2015 Dec 19;8(6):1382-92. Epub 2015 Oct 19.

From the Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam (J.N.t.S., R.C., C.E.C., A.H.G.D., J.R.d.G., H.L.T., A.A.M.W., J.M.T.d.B., P.F.H.M.v.D.); Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands (J.N.t.S., J.M.T.d.B.); L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux Segalen, Bordeaux, France (R.C.); and Pacific Rim Electrophysiology Research Institute, Los Angeles, CA (K.N.).

Background: Brugada syndrome (BrS) is characterized by a typical ECG pattern. We aimed to determine the pathophysiologic basis of the ST-segment in the BrS-ECG with data from various epicardial and endocardial right ventricular activation mapping procedures in 6 BrS patients and in 5 non-BrS controls.

Methods And Results: In 7 patients (2 BrS and 5 controls) with atrial fibrillation, an epicardial 8×6 electrode grid (interelectrode distance 1 mm) was placed epicardially on the right ventricular outflow tract (RVOT) before video-assisted thoracoscopic surgical pulmonary vein isolation. In 2 other BrS patients, endocardial, epicardial RV (CARTO), and body surface mapping was performed. In 2 additional BrS patients, we performed decremental preexcitation of the RVOT before endocardial RV mapping. During video-assisted thoracoscopic surgical pulmonary vein isolation and CARTO mapping, BrS patients (n=4) showed greater activation delay and more fractionated electrograms in the RVOT region than controls. Ajmaline administration increased the region with fractionated electrograms, as well as ST-segment elevation. Preexcitation of the RVOT (n=2) resulted in ECGs that supported the current-to-load mismatch hypothesis for ST-segment elevation. Body surface mapping showed that the area with ST-segment elevation anatomically correlated with the area of fractionated electrograms and activation delay at the RVOT epicardium.

Conclusions: ST-segment elevation and epicardial fractionation/conduction delay in BrS patients are most likely related to the same structural subepicardial abnormalities, but the mechanism is different. ST-segment elevation may be caused by current-to-load mismatch, whereas fractionated electrograms and conduction delay are expected to be caused by discontinuous conduction in the same area with abnormal myocardium.
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http://dx.doi.org/10.1161/CIRCEP.115.003366DOI Listing
December 2015
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