Anticoagulation for post-operative atrial fibrillation after isolated coronary artery bypass grafting: a meta-analysis.

BACKGROUND AND AIMS: This study aimed to evaluate clinical outcomes in patients developing post-operative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) and characterize variations in oral anticoagulation (OAC) use, benefits, and complications. METHODS: A systematic search identified studies on new-onset POAF after CABG and OAC initiation. Outcomes included risks of thromboembolic events, bleeding, and mortality. Furthermore, a meta-analysis was conducted on these outcomes, stratified by the use or non-use of OAC. RESULTS: The identified studies were all non-randomized. Among 1 698 307 CABG patients, POAF incidence ranged from 7.9% to 37.6%. Of all POAF patients, 15.5% received OAC. Within 30 days, thromboembolic events occurred at rates of 1.0% (POAF: 0.3%; non-POAF: 0.8%) with 2.0% mortality (POAF: 1.0%; non-POAF: 0.5%). Bleeding rates were 1.1% for POAF patients and 2.7% for non-POAF patients. Over a median of 4.6 years, POAF patients had 1.73 thromboembolic events, 3.39 mortality, and 2.00 bleeding events per 100 person-years; non-POAF patients had 1.14, 2.19, and 1.60, respectively. No significant differences in thromboembolic risks [effect size -0.11 (-0.36 to 0.13)] and mortality [effect size -0.07 (-0.21 to 0.07)] were observed between OAC users and non-users. However, OAC use was associated with higher bleeding risk [effect size 0.32 (0.06-0.58)]. CONCLUSIONS: In multiple timeframes following CABG, the incidence of complications in patients who develop POAF is low. The use of OAC in patients with POAF after CABG is associated with increased bleeding risk.

Strain-controlled electrophysiological wave propagation alters in silico scar-based substrate for ventricular tachycardia.

Introduction: Assessing a patient's risk of scar-based ventricular tachycardia (VT) after myocardial infarction is a challenging task. It can take months to years after infarction for VT to occur. Also, if selected for ablation therapy, success rates are low. Methods: Computational ventricular models have been presented previously to support VT risk assessment and to provide ablation guidance. In this study, an extension to such virtual-heart models is proposed to phenomenologically incorporate tissue remodeling driven by mechanical load. Strain amplitudes in the heart muscle are obtained from simulations of mechanics and are used to adjust the electrical conductivity. Results: The mechanics-driven adaptation of electrophysiology resulted in a more heterogeneous distribution of propagation velocities than that of standard models, which adapt electrophysiology in the structural substrate from medical images only. Moreover, conduction slowing was not only present in such a structural substrate, but extended in the adjacent functional border zone with impaired mechanics. This enlarged the volumes with high repolarization time gradients (≥10 ms/mm). However, maximum gradient values were not significantly affected. The enlarged volumes were localized along the structural substrate border, which lengthened the line of conduction block. The prolonged reentry pathways together with conduction slowing in functional regions increased VT cycle time, such that VT was easier to induce, and the number of recommended ablation sites increased from 3 to 5 locations. Discussion: Sensitivity testing showed an accurate model of strain-dependency to be critical for low ranges of conductivity. The model extension with mechanics-driven tissue remodeling is a potential approach to capture the evolution of the functional substrate and may offer insight into the progression of VT risk over time.

Rationale and design of the BECA project: Smartwatch-based activation of the chain of survival for out-of-hospital cardiac arrest.

Aim: Out-of-hospital cardiac arrest is a major health problem, and the overall survival rate is low (4.6%-16.4%). The initiation of the current chain of survival depends on the presence of a witness of the cardiac arrest, which is not present in 29.7%-63.4% of the cases. Furthermore, a delay in starting this chain is common in witnessed out-of-hospital cardiac arrest. This project aims to reduce morbidity and mortality due to out-of-hospital cardiac arrest by developing a smartwatch-based solution to expedite the chain of survival in the case of (un)witnessed out-of-hospital cardiac arrest. Methods: Within the 'Beating Cardiac Arrest' project, we aim to develop a demonstrator product that detects out-of-hospital cardiac arrest using photoplethysmography and accelerometer analysis, and autonomously alerts emergency medical services. A target group study will be performed to determine who benefits the most from this product. Furthermore, several clinical studies will be conducted to capture or simulate data on out-of-hospital cardiac arrest cases, as to develop detection algorithms and validate their diagnostic performance. For this, the product will be worn by patients at high risk for out-of-hospital cardiac arrest, by volunteers who will temporarily interrupt blood flow in their arm by inflating a blood pressure cuff, and by patients who undergo cardiac electrophysiologic and implantable cardioverter defibrillator testing procedures. Moreover, studies on psychosocial and ethical acceptability will be conducted, consisting of surveys, focus groups, and interviews. These studies will focus on end-user preferences and needs, to ensure that important individual and societal values are respected in the design process.

Increasing accuracy of pulse arrival time estimation in low frequency recordings.

Objective.Wearable devices that measure vital signals using photoplethysmography are becoming more commonplace. To reduce battery consumption, computational complexity, memory footprint or transmission bandwidth, companies of commercial wearable technologies are often looking to minimize the sampling frequency of the measured vital signals. One such vital signal of interest is the pulse arrival time (PAT), which is an indicator of blood pressure. To leverage this non-invasive and non-intrusive measurement data for use in clinical decision making, the accuracy of obtained PAT-parameters needs to increase in lower sampling frequency recordings. The aim of this paper is to develop a new strategy to estimate PAT at sampling frequencies up to 25 Hertz.Approach.The method applies template matching to leverage the random nature of sampling time and expected change in the PAT.Main results.The algorithm was tested on a publicly available dataset from 22 healthy volunteers, under sitting, walking and running conditions. The method significantly reduces both the mean and the standard deviation of the error when going to lower sampling frequencies by an average of 16.6% and 20.2%, respectively. Looking only at the sitting position, this reduction is even larger, increasing to an average of 22.2% and 48.8%, respectively.Significance.This new method shows promise in allowing more accurate estimation of PAT even in lower frequency recordings.

Prehospital risk assessment and direct transfer to a percutaneous coronary intervention centre in suspected acute coronary syndrome.

OBJECTIVE: Prehospital risk stratification and triage are currently not performed in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS). This may lead to prolonged time to revascularisation, increased duration of hospital admission and higher healthcare costs. The preHEART score (prehospital history, ECG, age, risk factors and point-of-care troponin score) can be used by emergency medical services (EMS) personnel for prehospital risk stratification and triage decisions in patients with NSTE-ACS. The aim of the current study was to evaluate the effect of prehospital risk stratification and direct transfer to a percutaneous coronary intervention (PCI) centre, based on the preHEART score, on time to final invasive diagnostics or culprit revascularisation. METHODS: Prospective, multicentre, two-cohort study in patients with suspected NSTE-ACS. The first cohort is observational (standard care), while the second (interventional) cohort includes patients who are stratified for direct transfer to either a PCI or a non-PCI centre based on their preHEART score. Risk stratification and triage are performed by EMS personnel. The primary endpoint of the study is time from first medical contact until final invasive diagnostics or revascularisation. Secondary endpoints are time from first medical contact until intracoronary angiography (ICA), duration of hospital admission, number of invasive diagnostics, number of inter-hospital transfers and major adverse cardiac events at 7 and 30 days. RESULTS: A total of 1069 patients were included. In the interventional cohort (n=577), time between final invasive diagnostics or revascularisation (42 (17-101) hours vs 20 (5-44) hours, p<0.001) and length of hospital admission (3 (2-5) days vs 2 (1-4) days, p=0.007) were shorter than in the observational cohort (n=492). In patients with NSTE-ACS in need for ICA or revascularisation, healthcare costs were reduced in the interventional cohort (€5599 (2978-9625) vs €4899 (2278-5947), p=0.02). CONCLUSION: Prehospital risk stratification and direct transfer to a PCI centre, based on the preHEART score, reduces time from first medical contact to final invasive diagnostics and revascularisation, reduces duration of hospital admission and decreases healthcare costs in patients with NSTE-ACS in need for ICA or revascularisation. TRIAL REGISTRATION: NCT05243485.

Arrhythmia mechanism dependent pulmonary vein ablation in paroxysmal atrial fibrillation.

Atrial fibrillation (AF) often requires invasive treatment by ablation to decrease symptom burden. The pulmonary veins (PV) are thought to trigger paroxysms of AF, and ablative PV isolation (PVI) is a cornerstone in AF treatment. However, incomplete PVI, where electrical conduction between the PV and left atrium (LA) is maintained, is curative of AF in a subset of patients. This implies that an antiarrhythmic effect other than electrical isolation between the PV and LA plays a role in AF prevention in these patients. We reason that the PV myocardium constitutes an arrhythmogenic substrate conducive to reentry in the patients with curative incomplete PVI. This PV substrate is amenable to ablation, even when conduction between the LA and PV persists. We propose that PV ablation strategies are differentiated to fit the arrhythmogenic mechanisms in the individual patient. PV substrate modification in patients with PV reentry may constitute a new therapeutic approach that is potentially simpler and more effective, in this subgroup of patients.

The prognostic value of quality of life in atrial fibrillation on patient value.

BACKGROUND: In this study, the prognostic value of AF-related quality of life (AFEQT) at baseline on Major Adverse Cardiovascular Events (MACE) and improvement of perceived symptoms (EHRA) was assessed. Furthermore, the relationship between QoL and AF-related hospitalizations was assessed. METHODS: A cohort of AF-patients diagnosed between November 2014 and October 2019 in four hospitals embedded within the Netherlands Heart Network were prospectively followed for 12 months. MACE was defined as stroke, myocardial infarction, heart failure and/or mortality. Subsequently, MACE, EHRA score improvement and AF-related hospitalizations between baseline and 12 months of follow-up were recorded. RESULTS: In total, 970 AF-patients were available for analysis. In analyses with patients with complete information on the confounder subset 36/687 (5.2%) AF-patients developed MACE, 190/432 (44.0%) improved in EHRA score and 189/510(37.1%) were hospitalized during 12 months of follow-up. Patients with a low AFEQT score at baseline more often developed MACE (OR(95%CI): 2.42(1.16-5.06)), more often improved in EHRA score (OR(95%CI): 4.55(2.45-8.44) and were more often hospitalized (OR(95%CI): 4.04(2.22-7.01)) during 12 months post diagnosis, compared to patients with a high AFEQT score at baseline. CONCLUSIONS: AF-patients with a lower quality of life at diagnosis more often develop MACE, more often improve on their symptoms and also were more often hospitalized, compared to AF-patients with a higher quality of life. This study highlights that the integration of patient-reported outcomes, such as quality of life, has the potential to be used as a prognostic indicator of the expected disease course for AF.

Reduction in atrial and pulmonary vein stretch as a therapeutic target for prevention of atrial fibrillation.

Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with increased mortality. Heart failure, hypertension, valvular disease, and obstructive sleep apnea are risk factors for incident AF. A common characteristic of these diseases is that they increase atrial wall stretch. Multiple experimental studies confirm a proarrhythmic effect of atrial stretch. Conversely, a reduction in stretch is antiarrhythmic. A therapeutic target for AF, therefore, lies in local reduction of atrial stretch. This review focuses on atrial stretch and its clinical associations in patients with AF and its downstream effects on electrophysiology. We discuss the possible application of targeted atrial stretch reduction in AF prevention. We conclude that a reduction in local atrial stretch should be considered an essential element in rhythm control.

From evidence-based medicine to digital twin technology for predicting ventricular tachycardia in ischaemic cardiomyopathy.

Survivors of myocardial infarction are at risk of life-threatening ventricular tachycardias (VTs) later in their lives. Current guidelines for implantable cardioverter defibrillators (ICDs) implantation to prevent VT-related sudden cardiac death is solely based on symptoms and left ventricular ejection fraction. Catheter ablation of scar-related VTs is performed following ICD therapy, reducing VTs, painful shocks, anxiety, depression and worsening heart failure. We postulate that better prediction of the occurrence and circuit of VT, will improve identification of patients at risk for VT and boost preventive ablation, reducing mortality and morbidity. For this purpose, multiple time-evolving aspects of the underlying pathophysiology, including the anatomical substrate, triggers and modulators, should be part of VT prediction models. We envision digital twins as a solution combining clinical expertise with three prediction approaches: evidence-based medicine (clinical practice), data-driven models (data science) and mechanistic models (biomedical engineering). This paper aims to create a mutual understanding between experts in the different fields by providing a comprehensive description of the clinical problem and the three approaches in an understandable manner, leveraging future collaborations and technological innovations for clinical decision support. Moreover, it defines open challenges and gains for digital twin solutions and discusses the potential of hybrid modelling.

Prehospital triage of patients with suspected non-ST-segment elevation acute coronary syndrome: Rationale and design of the TRIAGE-ACS study.

BACKGROUND: Patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are currently transported and admitted to the nearest emergency department (ED) for risk stratification, diagnostic workup and treatment. Although such patients with NSTE-ACS can benefit from direct transfer to a PCI center for early invasive treatment, no reliable prehospital triage tools are available. Recently, the PreHEART score has been validated in the PreHEART study for prehospital triage of patients with suspected NSTE-ACS. METHODS: The primary objective of the TRIAGE-ACS study, a prospective cohort study, is to determine whether prehospital triage using the PreHEART score can significantly reduce time from first medical contact to final diagnostics and revascularization in patients in need of coronary revascularization. The first cohort (control cohort; n = 500) is observatory and is used as a reference group for the second cohort. In the second cohort (interventional cohort; n = 500) patients are stratified in the ambulance for direct transfer to either a PCI or a non-PCI center, based on the PreHEART score. These two cohorts will be compared with each other. In total, 1000 patients will be included. Follow-up for endpoints will be performed by reviewing the medical record after 30 days, 1 year, and 2 years. CONCLUSION: The TRIAGE-ACS study is the first prospective study to investigate the impact of prehospital triage using the PreHEART score on time to final invasive diagnostics and treatment in patients with NSTE-ACS in need of revascularization by transferring high risk patients directly to a PCI center and patients at a low risk of having an NSTE-ACS to a non-PCI center. Such triage strategy could potentially result in optimization of regional care for all ACS patients.

Prehospital risk assessment in patients suspected of non-ST-segment elevation acute coronary syndrome: a systematic review and meta-analysis.

OBJECTIVE: To review, inventory and compare available diagnostic tools and investigate which tool has the best performance for prehospital risk assessment in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS: Systematic review and meta-analysis. Medline and Embase were searched up till 1 April 2021. Prospective studies with patients, suspected of NSTE-ACS, presenting in the primary care setting or by emergency medical services (EMS) were included. The most important exclusion criteria were studies including only patients with ST-elevation myocardial infarction and studies before 1995, the pretroponin era. The primary end point was the final hospital discharge diagnosis of NSTE-ACS or major adverse cardiac events (MACE) within 6 weeks. Risk of bias was evaluated by the Quality Assessment of Diagnostic Accuracy Studies Criteria. MAIN OUTCOME AND MEASURES: Sensitivity, specificity and likelihood ratio of findings for risk stratification in patients suspected of NSTE-ACS. RESULTS: In total, 15 prospective studies were included; these studies reflected in total 26 083 patients. No specific variables related to symptoms, physical examination or risk factors were useful in risk stratification for NSTE-ACS diagnosis. The most useful electrocardiographic finding was ST-segment depression (LR+3.85 (95% CI 2.58 to 5.76)). Point-of-care troponin was found to be a strong predictor for NSTE-ACS in primary care (LR+14.16 (95% CI 4.28 to 46.90) and EMS setting (LR+6.16 (95% CI 5.02 to 7.57)). Combined risk scores were the best for risk assessment in an NSTE-ACS. From the combined risk scores that can be used immediately in a prehospital setting, the PreHEART score, a validated combined risk score for prehospital use, derived from the HEART score (History, ECG, Age, Risk factors, Troponin), was most useful for risk stratification in patients with NSTE-ACS (LR+8.19 (95% CI 5.47 to 12.26)) and for identifying patients without ACS (LR-0.05 (95% CI 0.02 to 0.15)). DISCUSSION: Important study limitations were verification bias and heterogeneity between studies. In the prehospital setting, several diagnostic tools have been reported which could improve risk stratification, triage and early treatment in patients suspected for NSTE-ACS. On-site assessment of troponin and combined risk scores derived from the HEART score are strong predictors. These results support further studies to investigate the impact of these new tools on logistics and clinical outcome. FUNDING: This study is funded by ZonMw, the Dutch Organisation for Health Research and Development. TRIAL REGISTRATION NUMBER: This meta-analysis was published for registration in PROSPERO prior to starting (CRD York, CRD42021254122).

Age-dependency of EHRA improvement based on quality of life at diagnosis of atrial fibrillation.

BACKGROUND: In this study, the relationship between AF-related quality of life (AFEQT) at baseline in AF-patients and the improvement on perceived symptoms and general state of health (EHRA, European Heart Rhythm Association score) at 12 months was assessed across predefined age categories. METHODS: Between November 2014 and October 2019 patients diagnosed with AF de novo in four hospitals embedded within the Netherlands Heart Network were prospectively followed for 12 months. These AF-patients were categorized into quartiles based on their AFEQT score at diagnosis and EHRA score was measured at diagnosis and 12 months of follow-up. Stratified analyses were performed using age categories (<65 vs. ≥65 years; <75 vs. ≥75 years). RESULTS: In total, 203/483 (42.0%) AF-patients improved in EHRA score after 12 months of follow-up. AF-patients in the lowest AFEQT quartile were more likely to improve, compared to patients in the highest AFEQT quartile (OR [95%CI]:4.73 [2.63-8.50]). Furthermore, patients ≥65 years and patients <75 years at diagnosis with lower AFEQT scores at baseline were most likely to improve in EHRA score after 12 months, compared to similarly aged patients with higher AFEQT scores at baseline. CONCLUSION: The present study indicates that AF-patients with a lower quality of life at diagnosis were most likely to improve their EHRA score after 12 months. This effect was most prominent in patients ≥65 years of age and patients <75 years of age, compared to patients >65 and ≥75 years, respectively. Future research should focus on further defining characteristics of these age groups to enable the implementation of age-tailored treatment.

Medical Instrument Segmentation in 3D US by Hybrid Constrained Semi-Supervised Learning.

Medical instrument segmentation in 3D ultrasound is essential for image-guided intervention. However, to train a successful deep neural network for instrument segmentation, a large number of labeled images are required, which is expensive and time-consuming to obtain. In this article, we propose a semi-supervised learning (SSL) framework for instrument segmentation in 3D US, which requires much less annotation effort than the existing methods. To achieve the SSL learning, a Dual-UNet is proposed to segment the instrument. The Dual-UNet leverages unlabeled data using a novel hybrid loss function, consisting of uncertainty and contextual constraints. Specifically, the uncertainty constraints leverage the uncertainty estimation of the predictions of the UNet, and therefore improve the unlabeled information for SSL training. In addition, contextual constraints exploit the contextual information of the training images, which are used as the complementary information for voxel-wise uncertainty estimation. Extensive experiments on multiple ex-vivo and in-vivo datasets show that our proposed method achieves Dice score of about 68.6%-69.1% and the inference time of about 1 sec. per volume. These results are better than the state-of-the-art SSL methods and the inference time is comparable to the supervised approaches.

Regional implementation of atrial fibrillation screening: benefits and pitfalls.

Aims: Despite general awareness that screening for atrial fibrillation (AF) could reduce health hazards, large-scale implementation is lagging behind technological developments. As the successful implementation of a screening programme remains challenging, this study aims to identify facilitating and inhibiting factors from healthcare providers' perspectives. Methods and results: A mixed-methods approach was used to gather data among practice nurses in primary care in the southern region of the Netherlands to evaluate the implementation of an ongoing single-lead electrocardiogram (ECG)-based AF screening programme. Potential facilitating and inhibiting factors were evaluated using online questionnaires (N = 74/75%) and 14 (of 24) semi-structured in-depth interviews (58.3%). All analyses were performed using SPSS 26.0. In total, 16 682 screenings were performed on an eligible population of 64 000, and 100 new AF cases were detected. Facilitating factors included 'receiving clear instructions' (mean ± SD; 4.12 ± 1.05), 'easy use of the ECG-based device' (4.58 ± 0.68), and 'patient satisfaction' (4.22 ± 0.65). Inhibiting factors were 'time availability' (3.20 ± 1.10), 'insufficient feedback to the practice nurse' (2.15 ± 0.89), 'absence of coordination' (54%), and the 'lack of fitting policy' (32%). Conclusion: Large-scale regional implementation of an AF screening programme in primary care resulted in a low participation of all eligible patients. Based on the perceived barriers by healthcare providers, future AF screening programmes should create preconditions to fit the intervention into daily routines, appointing an overall project lead and a General Practitioner (GP) as a coordinator within every GP practice.

Profibrillatory Structural and Functional Properties of the Atrial-Pulmonary Junction in the Absence of Remodeling.

Background: Sole pulmonary vein (PV) isolation by ablation therapy prevents atrial fibrillation (AF) in patients with short episodes of AF and without comorbidities. Since incomplete PV isolation can be curative, we tested the hypothesis that the PV in the absence of remodeling and comorbidities contains structural and functional properties that are proarrhythmic for AF initiation by reentry. Methods: We performed percutaneous transvenous in vivo endocardial electrophysiological studies and quantitative histological analysis of PV from healthy sheep. Results: The proximal PV contained more myocytes than the distal PV and a higher percentage of collagen and fat tissue relative to myocytes than the left atrium. Local fractionated electrograms occurred in both the distal and proximal PVs, but a large local activation (>0.75 mV) was more often present in the proximal PV than in the distal PV (86 vs. 50% of electrograms, respectively, p = 0.017). Atrial arrhythmias (run of premature atrial complexes) occurred more often following the premature stimulation in the proximal PV than in the distal PV (p = 0.004). The diastolic stimulation threshold was higher in the proximal PV than in the distal PV (0.7 [0.3] vs. 0.4 [0.2] mA, (median [interquartile range]), p = 0.004). The refractory period was shorter in the proximal PV than in the distal PV (170 [50] vs. 248 [52] ms, p < 0.001). A linear relation existed between the gradient in refractoriness (distal-proximal) and atrial arrhythmia inducibility in the proximal PV. Conclusion: The structural and functional properties of the native atrial-PV junction differ from those of the distal PV. Atrial arrhythmias in the absence of arrhythmia-induced remodeling are caused by reentry in the atrial-PV junction. Ablative treatment of early paroxysmal AF, rather than complete isolation of focal arrhythmia, may be limited to inhibition of reentry.

Reduction in left atrial and pulmonary vein dimensions after ablation therapy is mediated by scar.

BACKGROUND: Ablative pulmonary vein isolation (PVI) decreases pulmonary vein (PV) and left atrial (LA) dimensions in atrial fibrillation (AF) patients. These changes are attributed to reverse structural remodeling following sinus rhythm restoration but evidence is lacking. We hypothesized that the downsizing is directly caused by the ablative energy and subsequent scar formation. METHODS: We studied cardiac magnetic resonance imaging in 21 paroxysmal AF patients before and 3 months after successful PVI and in healthy sheep (n = 12) before and after PVI of the right PV only. RESULTS: PVI decreased the PV diameter in patients and sheep by 11.0(10.3) and 9.2(11.0)%, (p < 0.001 and p = 0.020), respectively. The control left PV in sheep were unchanged. A linear correlation existed between the extent of PV scar and PVI-induced decrease in PV diameter in patients.After PVI, the LA volume decreased (103(38) vs. 92(31)ml, pre- vs. post-ablation, respectively, p = 0.006), while the right atrial (RA) volume was unchanged in patients. A decrease in active emptying fraction after ablation (26.5(10.7) vs. 21.8(10.6)%, pre- vs. post-ablation, p = 0.031) was associated with reduced contractility of the PV walls (p = 0.004). The contractility of the LA walls was unaltered (p = 0.749). CONCLUSION: The ablation-induced PV diameter reduction was similar in patients with AF and healthy sheep without AF and was associated with PV scar extent. The volume only decreased in LA and not RA after PVI, and wall contractility decreased only in ablated sites. Therefore, the PVI-induced atrial downsizing is caused by the ablative energy and subsequent scar formation.

Localized Pulmonary Vein Scar Promotes Atrial Fibrillation in High Left Atrial Pressure.

BACKGROUND: Pulmonary vein (PV) ablation is unsuccessful in atrial fibrillation (AF) patients with high left atrial (LA) pressure. Increased atrial stretch by increased pressure is proarrhythmic for AF, and myocardial scar alters wall deformation. We hypothesized that localized PV scar is proarrhythmic for AF in high LA pressure. METHODS: Radiofrequency energy was delivered locally in the right PV of healthy sheep. The sheep recovered for 4 months. Explanted hearts (n = 9 PV scar, n = 9 controls) were perfused with 1:4 blood:Tyrode's solution in a four-chamber working heart setup. Programmed PV stimulation was performed during low (∼12 mmHg) and high (∼25 mmHg) LA pressure. An AF inducibility index was calculated based on the number of induction attempts and the number of attempts causing AF (run of ≥ 20 premature atrial complexes). RESULTS: In high LA pressure, the presence of PV scar increased the AF inducibility index compared with control hearts (0.83 ± 0.20 vs. 0.38 ± 0.40 arb. unit, respectively, p = 0.014). The diastolic stimulation threshold in high LA pressure was higher (108 ± 23 vs. 77 ± 16 mA, respectively, p = 0.006), and its heterogeneity was increased in hearts with PV scar compared with controls. In high LA pressure, the refractory period was shorter in PV scar than in control hearts (178 ± 39 vs. 235 ± 48 ms, p = 0.011). CONCLUSION: Localized PV scar only in combination with increased LA pressure facilitated the inducibility of AF. This was associated with changes in tissue excitability remote from the PV scar. Localized PV ablation is potentially proarrhythmic in patients with increased LA pressure.

Self-Reported Onset of Paroxysmal Atrial Fibrillation Is Related to Sleeping Body Position.

Background: Because stretch of the atrial myocardium is proarrhythmic for atrial fibrillation (AF) and a left lateral body position increases atrial dimensions in humans, we hypothesized that left lateral recumbence is a frequent AF-triggering body position in AF patients. Methods: We performed a questionnaire study of symptomatic paroxysmal AF (episodes of AF < 1 week) patients scheduled for a first AF ablation therapy at Catharina Hospital, Eindhoven, the Netherlands and at University Hospital, Bordeaux, France. Results: Ninety-four symptomatic paroxysmal AF patients were included [mean age 61 ± 11 years, median AF history of 29(48) months, 31% were females]. Twenty-two percent of patients reported a specific body position as a trigger of their AF symptoms. The triggering body position was left lateral position in 57% of cases, supine position in 33%, right lateral position in 10%, and prone position in 5% (p = 0.003 overall difference in prevalence). Patients with positional AF had a higher body mass index compared to patients without nocturnal/positional AF [28.7(4.2) and 25.4(5.2) kg/m2, respectively, p = 0.025], but otherwise resembled these patients. Conclusion: Body position, and the left lateral position, in particular, is a common trigger of AF in symptomatic AF patients. Moreover, positional AF is associated with overweight. Understanding of the underlying mechanisms of positional AF can contribute to AF treatment and prevention.

The Blinding Period Following Ablation Therapy for Atrial Fibrillation: Proarrhythmic and Antiarrhythmic Pathophysiological Mechanisms.

Atrial fibrillation (AF) causes heart failure, ischemic strokes, and poor quality of life. The number of patients with AF is estimated to increase to 18 million in Europe in 2050. Pharmacological therapy does not cure AF in all patients. Ablative pulmonary vein isolation is recommended for patients with drug-resistant symptomatic paroxysmal AF but is successful in only about 60%. In patients in whom ablative therapy is successful on the long term, recurrence of AF may occur in the first weeks to months after pulmonary vein ablation. The early recurrence (or delayed cure) of AF is not understood but forms the basis for the generally accepted 3-month blinding (or blanking) period after ablation therapy, which is not included in the evaluation of the eventual success rate of the procedures. The underlying pathophysiological processes responsible for early recurrence and the delayed cure are unknown. The implicit assumption of the blinding period is that the AF mechanism in this period is different from the ablation-targeted AF mechanism (ectopy from the pulmonary veins). In this review, we evaluate the temporary and long-lasting pro- and antiarrhythmic effects of each of the pathophysiological processes and interventions (necrosis, ischemia, oxidative stress, edema, inflammation, autonomic nervous activity, tissue repair, mechanical remodeling, and use of antiarrhythmic drugs) occurring in the blinding period that can modulate AF mechanisms. We propose that stretch-reducing ablation scar is a permanent antiarrhythmic mechanism that develops during the blinding period and is the reason for delayed cure.

High microvascular resistance and reduced left atrial strain in patients with coronary microvascular dysfunction: The micro-strain study.

BACKGROUND: It is already known that high coronary microvascular resistance (Rµ) is linked to altered left ventricular stiffness and might be an early indicator of heart failure with preserved ejection fraction (HFpEF). Left atrial dysfunction, on the other hand, varies according to the grade of left ventricular diastolic dysfunction. This is the first study to use the latest development for invasive assessment of Rµ and to combine it with echocardiographic assessment of left atrial strain during reservoir phase (LASr) by speckle tracking in relation to left ventricular (LV) diastolic function. METHODS AND RESULTS: An invasive angiogram was performed in 97 patients because of suspected ANOCA. All patients underwent comprehensive echocardiography, yet image quality was poor in 15 patients leaving 82 patients to include in the final analysis. In order to compare Rµ with LASr values, patients were divided into 4 groups based upon normal values of Rµ as defined by Fournier et al. The mean LASr was plotted against the four resistance groups. The LASr was 48.6% in the lowest resistance group, and 40.1%, 36.3% and 30.1% in the low intermediate, high intermediate and high resistance group respectively. These differences were significant compared to the lowest resistance group (p < 0.05). Although higher Rµ groups showed more diastolic dysfunction, LASr was already decreased irrespective of the severity of diastolic dysfunction. CONCLUSION: This study shows a relationship between increased Rµ and reduced LASr, that seems to precede conventional measures of left ventricular diastolic dysfunction. This suggests that microvascular dysfunction might be an early indicator for the development of impaired LA function.