Search

In the Netherlands, concerns have been raised regarding the high unemployment rates and the lack of permanent positions for young medical specialists. In the current study, we present data on contemporary early career perspectives in the field of cardiology. We conducted a survey among 304 young cardiologists who completed their training between 2015 and 2020; the response rate was 91%. Our analysis revealed a low unemployment rate (0.3%). One, 3 and 5 years after registration, 81%, 41% and 18% of the respondents, respectively, had not gained a permanent position. Having conducted a fellowship significantly delayed the time to permanent position (hazard ratio (HR): 0.48; 95% confidence interval (CI): 0.34-0.67). For those who had conducted a fellowship, holding a PhD degree (HR: 1.95; 95% CI: 1.10-3.44), age (per year increase, HR: 0.90; 95% CI: 0.82-0.99) and training in an academic hospital (HR: 1.97; 95% CI: 1.10-3.52) were of significant influence on the likelihood of having a permanent position at 3 years of follow-up. These results showed a disturbing increase in time to permanent position compared with an earlier analysis. This trend justifies close monitoring of the labour market in the coming years. Solutions for this multifactorial problem in the field of cardiology and across the entire medical specialty spectrum should be explored., (© 2022. The Author(s).)

To assess transthoracic echocardiographic (TTE) left atrial (LA) strain parameters and their association with atrial fibrillation (AF) recurrence after thoracoscopic surgical ablation (SA) in patients in sinus rhythm (SR) or in AF at baseline. Patients participating in the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery trial were included. All patients underwent thoracoscopic pulmonary vein isolation with LA appendage exclusion and were randomized to ganglion plexus (GP) or no GP ablation. In TTEs performed before surgery, LA strain and mechanical dispersion (MD) of the LA reservoir and conduit phase in all patients, and of the contraction phase in patients in SR were obtained. Recurrence of AF was defined as any documented atrial tachyarrhythmia lasting > 30 s during one year of follow-up. Two hundred and four patients (58.6 ± 7.8 years, 73% male, 57% persistent AF) were included. At baseline TTE 121 (59%) were in SR and 83 (41%) had AF. Patients with AF recurrence had lower LA strain of the reservoir phase (13.0% vs. 16.6%; p =  < 0.001) and a less decrease in strain of the conduit phase (-9.0% vs. -11.8%; p = 0.006), regardless of rhythm. MD of the conduit phase was larger in patients with AF recurrence (79.4 vs. 43.5 ms; p = 0.012). Multivariate cox regression analysis demonstrated solely an association between LA strain of the reservoir phase and AF recurrence in patients in SR (HR 0.95, p = 0.046) or with AF (HR 0.90, p = 0.038). A reduction in LA strain of the reservoir phase prior to SA predicts recurrence of AF in both patients with SR or AF. Left atrial strain assessment may therefore add to a better patient selection for SA., (© 2022. The Author(s).)

In the Netherlands, concerns have been raised regarding the high unemployment rates and the lack of permanent positions for young medical specialists. In the current study, we present data on contemporary early career perspectives in the field of cardiology. We conducted a survey among 304 young cardiologists who completed their training between 2015 and 2020; the response rate was 91%. Our analysis revealed a low unemployment rate (0.3%). One, 3 and 5 years after registration, 81%, 41% and 18% of the respondents, respectively, had not gained a permanent position. Having conducted a fellowship significantly delayed the time to permanent position (hazard ratio (HR): 0.48; 95% confidence interval (CI): 0.34-0.67). For those who had conducted a fellowship, holding a PhD degree (HR: 1.95; 95% CI: 1.10-3.44), age (per year increase, HR: 0.90; 95% CI: 0.82-0.99) and training in an academic hospital (HR: 1.97; 95% CI: 1.10-3.52) were of significant influence on the likelihood of having a permanent position at 3 years of follow-up. These results showed a disturbing increase in time to permanent position compared with an earlier analysis. This trend justifies close monitoring of the labour market in the coming years. Solutions for this multifactorial problem in the field of cardiology and across the entire medical specialty spectrum should be explored., Supplementary Information: The online version of this article (10.1007/s12471-022-01736-1) contains supplementary material, which is available to authorized users., Competing Interests: Conflict of interestV.M.M. Vorselaars, M. Minneboo, W.C. Meijers, A.C. van der Heijden, D. Haroun, V.J.M. Baggen, W.R. Berger and G.P.J. van Hout declare that they have no competing interests., (© The Author(s) 2022.)

Introduction: Atrial fibrillation (AF) is the most common arrhythmia and imposes a high burden on the healthcare system. A nurse-led AF outpatient clinic may alleviate the burden on the cardiology outpatient clinic by triaging patients who need care by a cardiologist or general practitioner (GP). However, care and referral patterns after initial assessment in a nurse-led AF outpatient clinic are unknown. We examined the proportion of AF patients assessed in a nurse-led clinic without outpatient follow-up by a cardiologist., Methods: All patients with AF referred to our tertiary medical centre underwent cardiac work-up in the nurse-led AF outpatient clinic and were prospectively followed. Data on patient characteristics, rhythm monitoring and echocardiography were collected and described. Odds ratio (OR) for continuing care in the nurse-led AF outpatient clinic was calculated., Results: From 2014 to 2018, 478 consecutive individual patients were referred to the nurse-led AF outpatient clinic. After the initial cardiac work-up, 139 patients (29.1%) remained under nurse-led care and 121 (25.3%) were referred to a cardiologist and 218 (45.6%) to a GP. Patients who remained under nurse-led care were significantly younger, were more symptomatic, more often had paroxysmal AF and had less comorbidities than the other two groups. After multivariable testing, CHA 2 DS 2 -VASc score ≥ 2 was associated with discontinued nurse-led care (OR 0.57, 95% confidence interval 0.34-0.95)., Conclusion: After initial cardiac assessment in the nurse-led outpatient clinic, about half of the newly referred AF patients were referred back to their GP. This strategy may reduce the burden of AF patients on secondary or tertiary cardiology outpatient clinics., (© 2021. The Author(s).)

Background: Clinical outcome of pulmonary vein isolation (PVI) has been predominantly focused on the reoccurrence of atrial fibrillation (AF) and the maintenance of sinus rhythm. However, there has been a limited intermediate follow-up on health-related quality-of-life (HRQoL) of patients. Given the relatively high recurrence rate of persistent AF after PVI treatment, it is important to follow up with clinical outcomes on symptom improvement as well as health-related quality-of-life. This study was designed to investigate the recurrence rate of atrial tachyarrhythmia (ATa), AF-related symptoms and HRQoL after PVI in patients with persistent AF who were treated with the second generation cryoballoon., Methods: Total 148 patients participated in the study who were treated by PVI between 2013 and 2017 for persistent AF. All patients visited the out-patient clinic 2-5 years after PVI. During this visit all patients filled-out an AF Effect on Quality-of-life (AFEQT) questionnaire and a seven-day Holter was applied. All rhythm recordings acquired post ablation were collected and analysed, and the modified European Heart Rhythm Association score (mEHRA) scores were calculated before and after the ablation., Results: The average age of patients was 63±9 year old and 44 (27.9%) were female. Mean CHA2DS2 VASc score was 1.9±1.4, and moderate and severe left atrial (LA) dilation was present in 53 (36.1%) and 15 (10.2%) patients, respectively. After a follow-up of 3.7±1.0 years, 81 (54.7%) patients had an ATa recurrence and 35 (23.6%) patients underwent a repeat LA ablation. However, the mEHRA score significantly improved in 80.4% of the patients (p <0.001), with the median overall AFEQT score of 88.9 [70.4-97.2]., Conclusions: There is a considerable ATa recurrence rate after PVI of persistent AF at intermediate-term follow-up. However, our data indicate that PVI significantly improved AF-related symptoms and resulted in a high HRQoL for 2-5 years in patients with persistent AF., Competing Interests: D. Mol reports speaker/consultancy fee from Abbott. Dr. J.R. de Groot reports research grants through his institution from Abbott, Atricure, Boston Scientific, Bayer, Daichi Sankyo, Johnson&Johnson, and Medtronic. In addition, he reports speaker/consultancy fees from Atricure, Bayer, Daiichi Sankyo, Johnson&Johnson, Medtronic, Novartis, Servier. Dr. de Jong reports consultancy fees from Medtronic, and speaker fees from Daiichi-Sankyo and Bayer. All the grants and fees received by the authors are outside the submitted work.

Background: There are nationwide concerns about the unemployment rate among young Dutch cardiologists and the increase in temporary positions. Therefore, the aim of this study was to investigate the unemployment rate in this subgroup as well as the length of time between the end of their training and the acquisition of a permanent position., Methods: All cardiologists who completed their training between January 2015 and December 2018 were invited to fill in an online questionnaire about their demographic characteristics, professional profile and employment status. The unemployment rate was calculated and Kaplan-Meier curves were used to determine the time between the end of training and the first permanent contract., Results: In total, 174 participants were included (mean age 35 ± 3 years, 64% male, median follow-up 2.3 years (interquartile range 1.4-3.2 years)). The unemployment rate was 0.6% (n = 1). Only 12 participants (7%) started their career with a permanent position. The percentage of cardiologists with a temporary position was 82%, 61% and 33% at 1, 2 and 3 years, respectively. The percentage of cardiologists with a temporary position did not differ with regard to age, gender, holding a PhD degree or type of teaching institution attended (academic vs non-academic). Forty-four per cent of participants perceived the current job market to be problematic., Conclusions: The unemployment rate among young cardiologists in the Netherlands was low between 2015 and 2018. The vast majority of cardiologists start their career on a temporary contract. Three years later, 33% still hold temporary positions. Due to the resultant job insecurity, many young cardiologists describe the job market as problematic., (© 2021. The Author(s).)

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.

The COVID-19 pandemic has overwhelmed healthcare systems worldwide, and a large part of regular cardiology care came to a quick halt. A Dutch nationwide survey showed that 41% of cardiology residents suspended their training and worked at COVID-19 cohort units for up to 3 months. With tremendous flexibility, on-call schedules were altered and additional training was provided in order for residents to be directly available where needed most. These unprecedented times have taught them important lessons on crisis management. The momentum is used to incorporate novel tools for patient care. Moreover, their experience of pandemic and crisis management has provided future cardiologists with unique skills. This crisis will not be wasted; however, several challenges have to be overcome in the near future including, but not limited to, a second pandemic wave, a difficult labour market due to an economic recession, and limitations in educational opportunities.

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.

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 max ), 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 ex vivo 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 ( n = 6) or with ( n = 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 max 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 max 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 ( p = 0.036) compared to no change without ACh (56.7 ± 29.3 ms to 50.0 ± 21.9 ms, p = 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.

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., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

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)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Eight-mm ablation catheters are widely used in cavotricuspid isthmus ablation (CTI) for treatment of right sided atrial flutter. However a high success rate, these large ablation tips comes with adisadvantage of lower resolution of fractionated signals., Purpose: The aim of this study was to evaluate the additional diagnostic value of the electrograms recordedfrom mini electrodes (MEs) in an 8-mm ablation catheter tip during CTI., Methods: CTI-ablation procedures were compared retrospectively in two groups, namely, group A: the Abbott Safire 8-mm tip with a 3D mapping system (n =37) and group B: the Boston Scientific MiFi IntellaTip XP 8-mm tip without a 3D mapping system (n=13). We analyzedacute procedural success, ablation characteristics and recurrence rate at one-year follow-up. Electrograms from MEs were analyzedright before the onset of the critical ablation application that resulted in acute CTI-block. We determined whether these ME electrograms had additional diagnostic value in addition to of the 8-mm tip derivedelectrogram., Results: At the onset of the critical ablation application, the MEs had an important additional value in 3 out of 13 cases as local signals were sensed on the MEs that were not recorded by the 8-mm tip electrode. In 2cases the ME did not show local electrogramsalthough the ablationwas still effective. Acute procedural and long-term success wereobserved in all patients. No differences were found in time to bidirectional block, procedure time or fluoroscopic exposure., Conclusion: Our data show that signals recorded from the MEs had additional diagnostic value, but only in asmall percentage of the patients. We did not observe, although omitting 3D-mapping in the ME group, any differencebetween groups with regard to procedural or ablation characteristicsduring CTI-ablation.

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.

Background: Advanced atrial fibrillation (AF) patients have persistent AF, failed previous catheter ablation and/or an enlarged left atrium (LA), which is associated with a reduced success of AF ablation. Transthoracic echocardiography (TTE) and contrast enhanced magnetic resonance angiography (CE-MRA) are available to assess LA volume. However, it is unknown how these modalities relate in patients with advanced AF. We therefore compared the reproducibility of TTE and non-triggered CE-MRA in advanced AF patients and their ability to select patients with successful thoracoscopic AF ablation., Methods: Two independent observers measured LA volumes on 65 TTE and CE-MRA exams of advanced AF patients prior to AF ablation. Patients were followed after AF ablation with rhythm monitoring every 3 months for 1 year to determine AF recurrence. Inter-modality, inter- and intra-observer variability were determined using intraclass correlation coefficients (ICC). Receiver-operating characteristic (ROC) analysis was performed to determine sensitivity and specificity of TTE and CE-MRA volume and CE-MRA dimensions to identify patients with AF recurrence during follow-up., Results: LA enlargement ≥ 34 ml/m 2 was present in 60% of the patients. CE-MRA and TTE demonstrated a good correlation for LA volume assessment (intraclass correlation, ICC = 0.86; p < 0.001) with larger volumes consistently measured by CE-MRA. Major discrepancies were mostly attributed to TTE acquisition. Craniocaudal enlargement discriminated patients with AF recurrence (AUC 0.67 [95% CI 0.55-0.85], p = 0.01)., Conclusions: Non-triggered CE-MRA is a viable and reproducible 3D alternative for 2D TTE to assess LA volume in advanced AF patients. Craniocaudal enlargement was the only discriminator of AF recurrence after AF ablation.

Objective: The Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) study did not find a significant beneficial effect of intensive systolic blood pressure (SBP) lowering on cardiovascular events in hypertensive patients with type 2 diabetes mellitus (T2DM), while the Systolic Blood Pressure Intervention Trial (SPRINT) did find a significant beneficial effect in patients without T2DM. The objective of this analysis was to assess the effect of both T2DM and baseline cardiovascular disease risk on the treatment effect of intensive blood pressure lowering., Research Design and Methods: The individual patient data from the ACCORD-BP and SPRINT studies were pooled and follow-up durations harmonized. Both studies randomized hypertensive patients to an SBP target of <120 mmHg or a target of <140 mmHg. The composite primary end point consisted of unstable angina, myocardial infarction, acute heart failure, stroke, and cardiovascular death. The interaction between intensive blood pressure lowering and both T2DM and 10-year cardiovascular risk was assessed using Cox proportional hazards models., Results: The cohort consisted of 14,094 patients with mean age 66 ± 8.9 years and mean baseline SBP 139.5 ± 15.6 mmHg; 33.6% had T2DM. The hazard ratio for the primary composite end point was 0.82 (95% CI 0.73-0.93), P = 0.0017. The interaction between intensive blood pressure lowering and T2DM was nonsignificant ( P = 0.13). The 10-year cardiovascular risk was higher in primary prevention patients with T2DM, but risk did not interact with the treatment effect ( P = 0.84)., Conclusions: Intensive blood pressure lowering may have a similar favorable effect and appears to decrease cardiovascular events in both patients with and patients without T2DM., (© 2018 by the American Diabetes Association.)

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.

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., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Low systolic blood pressure (SBP) values are associated with an increased risk of cardiovascular events, giving rise to the so-called J-curve phenomenon. We assessed the association between on-treatment SBP levels, cardiovascular events, and all-cause mortality in patients randomized to different SBP targets., Methods: Data from 2 large randomized trials that randomly allocated hypertensive patients at high risk for cardiovascular disease to intensive (SBP<120 mm Hg) or conventional (SBP<140 mm Hg) treatment were pooled and harmonized for outcomes and follow-up duration. Using natural cubic splines, we plotted the hazard ratio for all-cause mortality and cardiovascular events against the mean on-treatment SBP per treatment group., Results: The pooled data consisted of 194 875 on-treatment SBP measurements in 13 946 patients (98.9%). During a median follow-up of 3.3 years, cardiovascular events occurred in 1014 patients (7.3%), and 502 patients died (3.7%). For both blood pressure targets, an identical shape of the J curve was present, with a nadir for cardiovascular events and all-cause mortality just below the SBP target. Patients in the lowest SBP stratum were older, had a higher body mass index, smoked more often, and had a higher frequency of diabetes mellitus and cardiovascular events., Conclusions: Low on-treatment SBP levels are associated with increased cardiovascular events and all-cause mortality. This association is independent of the attained blood pressure level because the J curve aligns with the SBP target. Our results suggest that the benefit or risk associated with intensive blood pressure-lowering treatment can be established only via randomized clinical trials., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01206062 and NCT00000620., (© 2017 American Heart Association, Inc.)

Background: Monosodium glutamate (MSG), also referred to as Vetsin or E621, is a flavour enhancer frequently used in Asian cuisine and abundantly present in the famous Chinese dish Peking duck. MSG is notorious for triggering the onset of the so-called 'Chinese restaurant syndrome' (CRS), a complex of unpleasant symptoms, which might include flushing, sweating and the onset of atrial fibrillation (AF). This study aims to determine the effects of MSG on the occurrence of AF., Methods: We conducted a placebo self-controlled single-arm study in the Academic Medical Centre in Amsterdam. We included paroxysmal AF patients who reported a consistent onset of AF upon MSG intake. During three admissions, participants were subsequently administered: placebo, 1.5 g and 3 g MSG. If AF was recorded after the dose of 1.5 g MSG, patients were given another placebo instead of 3 g MSG. The primary outcome was the onset of AF registered by 24-hour Holter monitoring. The secondary outcomes were any other arrhythmia and the onset of CRS defined as two or more symptoms of CRS after MSG intake., Results: Six men participated in the study. Both 1.5 g and 3 g MSG were unrelated to CRS, arrhythmias or AF occurrence., Conclusion: Peking duck can be put on the Christmas menu without risking guests to be admitted to the emergency department with new episodes of AF.

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., (© 2017 Wiley Periodicals, Inc.)

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with pronounced morbidity and mortality. Its prevalence, expected to further increase for the forthcoming years, and associated frequent hospitalizations turn AF into a major health problem. Structural and electrical atrial remodelling underlie the substrate for AF, but the exact mechanisms driving this remodelling remain incompletely understood. Recent studies have shown that microRNAs (miRNA), short non-coding RNAs that regulate gene expression, may be involved in the pathophysiology of AF. MiRNAs have been implicated in AF-induced ion channel remodelling and fibrosis. MiRNAs could therefore provide insight into AF pathophysiology or become novel targets for therapy with miRNA mimics or anti-miRNAs. Moreover, circulating miRNAs have been suggested as a new class of diagnostic and prognostic biomarkers of AF. However, the origin and function of miRNAs in tissue and plasma frequently remain unknown and studies investigating the role of miRNAs in AF vary in design and focus and even present contradicting results. Here, we provide a systematic review of the available clinical and functional studies investigating the tissue and plasma miRNAs in AF and will thereafter discuss the potential of miRNAs as biomarkers or novel therapeutic targets in AF.

Background: Despite advances in therapeutic interventions AF remains a progressive and symptomatic disease. Therefore, novel therapeutic interventions targeting the underlying arrhythmogenic substrate for AF is needed. Atrial fibrosis is an important component of the arrhythmogenic substrate of AF and may be initiated by aldosterone binding to the mineralocorticoid receptor. We hypothesized that aldosterone pathway blockade with mineralocorticoid receptor antagonists (MRA) reduces atrial fibrosis, and thus AF., Methods: We searched OVID MEDLINE, OVID EMBASE and the Cochrane Central Register of Controlled Trials from inception to June 10th, 2016 for randomized controlled trials (RCT) and observational studies addressing MRA and providing information on AF occurrence. Two independent reviewers selected and appraised the data. We performed random-effects meta-analyses. Summary odds ratios (OR) with 95% confidence intervals (CI) were calculated., Results: We included 14 studies, 5 RCT and 9 observational cohorts, with a cumulative number of 5332 patients (male: 74.9%, age: 65.3years); 2397 (45.0%) received an MRA (spironolactone or eplerenone). During follow-up, 204 (8.5%) patients treated with MRAs, developed AF, compared to 547 (18.6%) patients, without MRA treatment. Meta-analyses showed a significant overall reduction of AF risk in MRA treated patients (OR: 0.48 CI: 0.38-0.60 p<0.001), including a reduction of new-onset AF (OR: 0.52 CI: 0.37-0.74 p<0.001) and recurrent AF (OR: 0.37 CI: 0.24-0.57 p<0.001), but not post-operative AF (POAF) (OR: 0.60 CI: 0.33-1.09 p=0.09)., Conclusions: MRAs significantly reduce new-onset AF and recurrent AF, but not POAF. MRA treatment can be considered an additive therapeutic strategy in AF., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

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)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Pulmonary vein isolation (PVI) aims at eliminating symptomatic atrial fibrillation. In this regard, the most relevant indication for this procedure is the reduction of symptoms and improvement of quality of life (QoL) in patients who remain symptomatic despite antiarrhythmic drug treatment. We investigated the relation between documented atrial fibrillation recurrences and QoL in patients after PVI., Methods: One hundred and six PVIs were performed in 99 patients. Follow-up was mainly performed at referring hospitals. Short Form 36 (SF-36) QoL questionnaires were completed before and 1 year after PVI. Electrocardiographic recordings from the first postprocedural year were retrospectively collected, 3 months blanking excluded. Atrial fibrillation recurrence was defined as any recurrence of atrial arrhythmia documented on ECG or 24-h-Holter., Results: Before PVI, patients had lower QoL than the general Dutch population in 7/8 SF-36 questionnaire subscales (sumQoL 419.4 ± 161 vs. 617.9, P < 0.001). Atrial fibrillation recurred in 52 (49%) patients. In these patients, four subscales increased following PVI (physical functioning P < 0.001, role physical P = 0.006, bodily pain P = 0.011 and social functioning P = 0.047). SumQoL remained lower than the general Dutch population (546.7 ± 157, P = 0.003). In patients without documented recurrences, QoL improved to a level similar to that of the general Dutch population (602.9 ± 148; P = 0.46). The number of electrocardiographic recordings was lower in the group without documented recurrences (2.5 ± 1.8 vs. 3.8 ± 1.7, P = 0.002)., Conclusion: In patients without documentation of atrial fibrillation, QoL increased up to the level of the general population after PVI, but it remained lower in patients with recurrences. In the latter group more ECGs were done, suggesting that QoL relates particularly to symptomatic episodes. Improvement of QoL is therefore an important attribute of PVI.

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., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrosis is an important component of the arrhythmogenic substrate in patients with atrial fibrillation (AF). We studied the effect of interstitial fibrosis on conduction velocity (CV) in the left atrial appendage of patients with AF., Methods and Results: Thirty-five left atrial appendages were obtained during AF surgery. Preparations were superfused and stimulated at 100 beats per minute. Activation was recorded with optical mapping. Longitudinal CV (CVL), transverse CV (CVT), and activation times (> 2 mm distance) were measured. Interstitial collagen was quantified and graded qualitatively. The presence of fibroblasts and myofibroblasts was assessed immunohistochemically. Mean CVL was 0.55 ± 0.22 m/s, mean CVT was 0.25 ± 0.15 m/s, and the mean activation time was 9.31 ± 5.45 ms. The amount of fibrosis was unrelated to CV or patient characteristics. CVL was higher in left atrial appendages with thick compared with thin interstitial collagen strands (0.77 ± 0.22 versus 0.48 ± 0.19 m/s; P = 0.012), which were more frequently present in persistent patients with AF. CVT was not significantly different (P = 0.47), but activation time was 14.93 ± 4.12 versus 7.95 ± 4.12 ms in patients with thick versus thin interstitial collagen strands, respectively (P = 0.004). Fibroblasts were abundantly present and were associated with the presence of thick interstitial collagen strands (P = 0.008). Myofibroblasts were not detected in the left atrial appendage., Conclusions: In patients with AF, thick interstitial collagen strands are associated with higher CVL and increased activation time. Our observations demonstrate that the severity and structure of local interstitial fibrosis is associated with atrial conduction abnormalities, presenting an arrhythmogenic substrate for atrial re-entry., (© 2015 American Heart Association, Inc.)

Background: In patients with atrial fibrillation (AF), the autonomic nervous system is supposed to play an role in triggering AF; however, little is known of the effect on atrial conduction characteristics., Objective: The purpose of this study was to study the effect of ganglionic plexus (GP) stimulation during sinus rhythm on atrial and pulmonary vein conduction in patients during thoracoscopic surgery for AF METHODS: In 25 patients, the anterior right ganglionic plexus (ARGP) was stimulated (16 Hz, at 1, 2, and 5 mA). Epicardial electrograms were recorded using a 48-electrode map from the right pulmonary vein (RPV) or right atrial (RA). Intra-atrial activation time (IAT), local activation time (LAT), and inhomogeneity of conduction (IIC) were determined. ECG parameters (P-P, P-R interval) were measured., Results: P-P interval was 956 ± 157 ms (range 768-1368 ms), and P-R interval was 203 ± 37 ms (range 136-280 ms). After ARGP stimulation, a short-lasting increase of P-P interval was observed, more prominent at higher output (1 mA = 82 ms, 2 mA = 180 ms, 5 mA = 268 ms, all P <.01 vs baseline). P-R interval remained unchanged. IAT was 34.4 ms (range 5.6-50.3 ms) at the RA and 105.8 ms (range 79.7-163.3 ms) at the RPV. After 1-mA stimulation IAT increased, in patients taking beta-blockers (P = .001), or it decreased, and this change persisted after subsequent stimulation at higher current (1 mA, P = .001; 2 mA, P = .401; 5 mA, P = .593). Similar changes were observed for LAT and IIC., Conclusion: ARGP stimulation results in a short-lasting, output-dependent decrease in sinus node frequency due to a parasympathetic response. Stimulation of the ARGP induced a prolonged increase or decrease in conduction characteristics in patients with AF, consistent with a persistent differential parasympathetic and/or sympathetic response., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Although the majority of patients with atrial fibrillation and an indication for non-pharmacological therapy is treated with catheter ablation, thoracoscopic surgery is an emerging technique that aims at combining the results of the classic Cox Maze operation with a less invasive approach. Recurrences after thoracoscopic surgery have been mainly ascribed to incomplete ablation lines, but literature on electrophysiological confirmation of thoracoscopic pulmonary vein isolation is limited. Currently, surgical confirmation of uni- or bidirectional conduction block may be hampered by insufficient resolution of the mapping material available. Additionally uncertainty remains on the precise lesions sets required, and how to tailor them to individual patients. In hybrid procedures, electrophysiologists and surgeons join forces to combine their expertise and skills which may lead to increased procedural success rates by minimizing the chance of incomplete PV isolation or absence of conduction block across an alternative ablation line. Here we describe techniques for thoracoscopic mapping and present a literature review.

Background: Prolongation of the QT interval after exercise can be used to help diagnose long-QT syndrome, especially when the resting QT interval is borderline. The aim of this study was to determine the normal ranges for QT and corrected QT in the recovery phase after exercise in children., Methods and Results: Ninety-four volunteer boys and girls aged 8 to < 17 years without any history of heart disease underwent exercise testing and had a 12-lead ECG performed in the supine position for 10 minutes of recovery. The QT was measured using a standardized tangent method, with the baseline defined as the Q-Q line. The recovery QT was maximally short at 1 minute of recovery in 93 of 94 children then lengthened and stabilized at 4 to 5 minutes recovery. The recovery QT lengthens as heart rate decreases in an approximately linear fashion with a mean increase of 15 ms per 10-beat decrease in heart rate. The 98 th percentiles for the corrected QT using the Bazett formula during minutes 4 to 6 in recovery were from 482 to 491 ms. There was excellent intraobserver and interobserver reliability, with intraclass correlation coefficients of 0.95 and 0.88, respectively., Conclusions: There is substantial individual variability of the normal repolarization process in the postexercise recovery period in children. The study provides a reference for normal responses for similar populations using a specific measurement protocol that can be easily applied.