Primary cilia suppress the fibrotic activity of atrial fibroblasts from patients with atrial fibrillation in vitro.

Atrial fibrosis serves as an arrhythmogenic substrate in atrial fibrillation (AF) and contributes to AF persistence. Treating atrial fibrosis is challenging because atrial fibroblast activity is multifactorial. We hypothesized that the primary cilium regulates the profibrotic response of AF atrial fibroblasts, and explored therapeutic potentials of targeting primary cilia to treat fibrosis in AF. We included 25 patients without AF (non-AF) and 26 persistent AF patients (AF). Immunohistochemistry using a subset of the patients (non-AF: n = 10, AF: n = 10) showed less ciliated fibroblasts in AF versus non-AF. Acetylated α-tubulin protein levels were decreased in AF, while the gene expressions of AURKA and NEDD9 were highly increased in AF patients' left atrium. Loss of primary cilia in human atrial fibroblasts through IFT88 knockdown enhanced expression of ECM genes, including FN1 and COL1A1. Remarkably, restoration or elongation of primary cilia by an AURKA selective inhibitor or lithium chloride, respectively, prevented the increased expression of ECM genes induced by different profibrotic cytokines in atrial fibroblasts of AF patients. Our data reveal a novel mechanism underlying fibrotic substrate formation via primary cilia loss in AF atrial fibroblasts and suggest a therapeutic potential for abrogating atrial fibrosis by restoring primary cilia.

Atrial epicardial adipose tissue abundantly secretes myeloperoxidase and activates atrial fibroblasts in patients with atrial fibrillation.

BACKGROUND: Epicardial adipose tissue (EAT) secretome induces fibrosis. Fibrosis, primarily extracellular matrix (ECM) produced by fibroblasts, creates a substrate for atrial fibrillation (AF). Whether the EAT secretome from patients with AF activates human atrial fibroblasts and through which components, remains unexplored. RESEARCH AIMS: (a) To investigate if the EAT secretome from patients with versus without AF increases ECM production in atrial fibroblasts. (b) To identify profibrotic proteins and processes in the EAT secretome and EAT from patients with, who will develop (future onset), and without AF. METHODS: Atrial EAT was obtainded during thoracoscopic ablation (AF, n = 20), or open-heart surgery (future onset and non-AF, n = 35). ECM gene expression of human atrial fibroblasts exposed to the EAT secretome and the proteomes of EAT secretome and EAT were assessed in patients with and without AF. Myeloperoxidase and neutrophil extracellular traps (NETs) were assessed immunohistochemically in patients with paroxysmal, persistent, future onset, and those who remain free of AF (non-AF). RESULTS: The expression of COL1A1 and FN1 in fibroblasts exposed to secretome from patients with AF was 3.7 and 4.7 times higher than in patients without AF (p < 0.05). Myeloperoxidase was the most increased protein in the EAT secretome and EAT from patients with versus without AF (FC 18.07 and 21.57, p < 0.005), as was the gene-set neutrophil degranulation. Immunohistochemically, myeloperoxidase was highest in persistent (FC 13.3, p < 0.0001) and increased in future onset AF (FC 2.4, p = 0.02) versus non-AF. Myeloperoxidase aggregated subepicardially and around fibrofatty infiltrates. NETs were increased in patients with persistent versus non-AF (p = 0.03). CONCLUSION: In AF, the EAT secretome induces ECM gene expression in atrial fibroblasts and contains abundant myeloperoxidase. EAT myeloperoxidase was increased prior to AF onset, and both myeloperoxidase and NETs were highest in persistent AF, highlighting the role of EAT neutrophils in the pathophysiology of AF.

Effect of the machine learning-derived Hypotension Prediction Index (HPI) combined with diagnostic guidance versus standard care on depth and duration of intraoperative and postoperative hypotension in elective cardiac surgery patients: HYPE-2 - study protocol of a randomised clinical trial.

INTRODUCTION: Hypotension is common during cardiac surgery and often persists postoperatively in the intensive care unit (ICU). Still, treatment is mainly reactive, causing a delay in its management. The Hypotension Prediction Index (HPI) can predict hypotension with high accuracy. Using the HPI combined with a guidance protocol resulted in a significant reduction in the severity of hypotension in four non-cardiac surgery trials. This randomised trial aims to evaluate the effectiveness of the HPI in combination with a diagnostic guidance protocol on reducing the occurrence and severity of hypotension during coronary artery bypass grafting (CABG) surgery and subsequent ICU admission. METHODS AND ANALYSIS: This is a single-centre, randomised clinical trial in adult patients undergoing elective on-pump CABG surgery with a target mean arterial pressure of 65 mm Hg. One hundred and thirty patients will be randomly allocated in a 1:1 ratio to either the intervention or control group. In both groups, a HemoSphere patient monitor with embedded HPI software will be connected to the arterial line. In the intervention group, HPI values of 75 or above will initiate the diagnostic guidance protocol, both intraoperatively and postoperatively in the ICU during mechanical ventilation. In the control group, the HemoSphere patient monitor will be covered and silenced. The primary outcome is the time-weighted average of hypotension during the combined study phases. ETHICS AND DISSEMINATION: The medical research ethics committee and the institutional review board of the Amsterdam UMC, location AMC, the Netherlands, approved the trial protocol (NL76236.018.21). No publication restrictions apply, and the study results will be disseminated through a peer-reviewed journal. TRIAL REGISTRATION NUMBER: The Netherlands Trial Register (NL9449), ClinicalTrials.gov (NCT05821647).

A failed catheter ablation of atrial fibrillation is associated with more advanced remodeling and reduced efficacy of further thoracoscopic ablation.

INTRODUCTION AND OBJECTIVES: Recent observations suggest that patients with a previous failed catheter ablation have an increased risk of atrial fibrillation (AF) recurrence after subsequent thoracoscopic AF ablation. We assessed the risk of AF recurrence in patients with a previous failed catheter ablation undergoing thoracoscopic ablation. METHODS: We included patients from 3 medical centers. To correct for potential heterogeneity, we performed propensity matching to compare AF freedom (freedom from any atrial tachyarrhythmia> 30 s during 1-year follow-up). Left atrial appendage tissue was analyzed for collagen distribution. RESULTS: A total of 705 patients were included, and 183 had a previous failed catheter ablation. These patients had fewer risk factors for AF recurrence than ablation naïve controls: smaller indexed left atrial volume (40.9± 12.5 vs 43.0±12.5 mL/m2, P=.048), less congestive heart failure (1.5% vs 8.9%, P=.001), and less persistent AF (52.2% vs 60.3%, P=.067). However, AF history duration was longer in patients with a previous failed catheter ablation (6.5 [4-10.5] vs 4 [2-8] years; P<.001). In propensity matched analysis, patients with a failed catheter ablation were at a 68% higher AF recurrence risk (OR, 1.68; 95%CI, 1.20-2.15; P=.034). AF freedom was 61.1% in patients with a previous failed catheter ablation vs 72.5% in ablation naïve matched controls. On histology of the left atrial appendage (n=198), patients with a failed catheter ablation had a higher density of collagen fibers. CONCLUSIONS: Patients with a prior failed catheter ablation had fewer risk factors for AF recurrence but more frequently had AF recurrence after thoracoscopic AF ablation than ablation naïve patients. This may in part be explained by more progressed, subclinical, atrial fibrosis formation.

Left atrial strain and recurrence of atrial fibrillation after thoracoscopic surgical ablation: a subanalysis of the AFACT study.

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.

Autologous red blood cell transfusion does not result in a more profound increase in pulmonary capillary wedge pressure compared to saline in critically ill patients: A randomized crossover trial.

BACKGROUND AND OBJECTIVES: Transfusion-associated circulatory overload (TACO) is a major cause of severe transfusion-related morbidity. Transfusion of red blood cells (RBCs) has been shown to induce hydrostatic pressure overload. It is unclear which product-specific factors contribute. We set out to determine the effect of autologous RBC transfusion versus saline on pulmonary capillary wedge pressure (PCWP) change. MATERIALS AND METHODS: In a randomized crossover trial, patients who had undergone coronary bypass surgery were allocated to treatment post-operatively in the intensive care unit with either an initial 300 ml autologous RBC transfusion (salvaged during surgery) or 300 ml saline infusion first, followed by the other. Primary outcome was the difference in PCWP change. Secondary outcome measures were the difference in extra-vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). RESULTS: Change in PCWP was not higher after autologous RBC transfusion compared to saline (ΔPCWP 0.3 ± 0.4 vs. 0.1 ± 0.4 mmHg). ΔEVLWI and ΔPVPI were significantly decreased after autologous RBC transfusion compared to saline (ΔEVLWI -1.6 ± 0.6 vs. 0.2 ± 0.4, p = 0.02; ΔPVPI -0.3 ± 0.1 vs. 0.0 ± 0.1, p = 0.01). Haemodynamic variables and colloid osmotic pressure were not different for autologous RBC transfusion versus saline. CONCLUSION: Transfusion of autologous RBCs did not result in a more profound increase in PCWP compared to saline. RBC transfusion resulted in a decrease of EVLWI and PVPI compared to saline. Our data suggest that transfusing autologous RBCs may lead to less pulmonary oedema compared to saline. Future studies with allogeneic RBCs are needed to investigate other factors that may mediate the increase of PCWP, resulting in TACO.

Persistent phrenic nerve palsy after atrial fibrillation ablation: Follow-up data from The Netherlands Heart Registration.

BACKGROUND: Persistent phrenic nerve palsy (PNP) is an established complication of atrial fibrillation (AF) ablation, especially during cryoballoon and thoracoscopic ablation. Data on persistent PNP reversibility is limited because most patients recover <24 h. This study aims to investigate persistent PNP recovery, freedom of PNP-related symptoms after AF ablation and identify baseline variables associated with the occurrence and early PNP recovery in a large nationwide registry study. METHODS: In this study, we used data from the Netherlands Heart Registration, comprising data from 9549 catheter and thoracoscopic AF ablations performed in 2016 and 2017. PNP data was available of 7433 procedures, and additional follow-up data were collected for patients who developed persistent PNP. RESULTS: Overall, the mean age was 62 ± 10 years, and 67.7% were male. Fifty-four (0.7%) patients developed persistent PNP and follow-up was available in 44 (81.5%) patients. PNP incidence was 0.07%, 0.29%, 1.41%, and 1.25%, respectively for patients treated with conventional-RF, phased-RF, cryoballoon, and thoracoscopic ablation respectively. Seventy-one percent of the patients fully recovered, and 86% were free of PNP-related symptoms after a median follow-up of 203 (113-351) and 184 (82-359) days, respectively. Female sex, cryoballoon, and thoracoscopic ablation were associated with a higher risk to develop PNP. Patients with PNP recovering ≤180 days had a larger left atrium volume index than those with late or no recovery. CONCLUSION: After AF ablation, persistent PNP recovers in the majority of patients, and most are free of symptoms. Female patients and patients treated with cryoballoon or thoracoscopic ablation are more prone to develop PNP.

Perioperative Care Standards in Cardiac Surgery Patients Aiming at Enhancing Recovery: A Nationwide Survey in the Netherlands and Belgium.

OBJECTIVE: The aim of this survey was to describe existing perioperative care standards and best practices in the Netherlands and Belgium. DESIGN: An online survey was followed up by an in-depth personal interview. The main outcomes were the existing standards of perioperative care for patients undergoing cardiac surgery. SETTING: The online survey and subsequent interviews were targeted to one representative in the intensive care unit (ICU), cardiac surgery, and anesthesiology department from each cardiac surgical center in the Netherlands and Belgium. PARTICIPANTS: A representative intensive care physician, cardiac surgeon, and cardiac anesthesiologist. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The response rate was 60% (71% for the Netherlands, and 44% in Belgium). Agreement across centers was found for discontinuation of proton-pump inhibitors (80%) and avoiding intra- and postoperative (92%) nonsteroidal antiinflammatory drugs. Additionally, 98% of respondents stated that physiotherapy should be started immediately in the ICU. Major divergence was found for elements such as the discontinuation of angiotensin-converting enzyme inhibitors (55%) or the postoperative use of chest support vests (44%). CONCLUSIONS: The authors demonstrated a wide range of different local protocols. Strategies differed among disciplines, hospitals, and countries. This emphasized the need for the implementation of a more universal protocol to further reduce variance and improve recovery practices. This nationwide survey was the first of its kind simultaneously studying best practices for cardiac surgery through the entire care pathway at the advent of Enhanced Recovery After Surgery (ERAS) Cardiac implementation. A multinational randomized controlled trial to test the implementation of an evidence-based ERAS Cardiac protocol is the next step to pave the way for further outcome improvements in this high-risk population.

Are Thoracic Aortic Aneurysm Patients at Increased Risk for Cardiovascular Diseases?

Objectives: Abdominal aortic aneurysms are associated with a sharply increased cardiovascular risk. Cardiovascular risk management is therefore recommended in prevailing guidelines for abdominal aneurysm patients. It has been hypothesized that associated risk relates to loss of aortic compliance. If this hypothesis is correct, observations for abdominal aneurysms would also apply to thoracic aortic aneurysms. The objective of this study is to test whether thoracic aneurysms are also associated with an increased cardiovascular risk burden. Methods: Patients who underwent aortic valve or root surgery were included in the study (n = 239). Cardiovascular risk factors were studied and atherosclerosis was scored based on the preoperative coronary angiographies. Multivariate analyses were performed, controlling for cardiovascular risk factors and aortic valve morphology. Comparisons were made with the age- and gender-matched general population and non-aneurysm patients as control groups. A thoracic aortic aneurysm was defined as an aortic aneurysm of ≥45 mm. Results: Thoracic aortic aneurysm was not associated with an increased coronary atherosclerotic burden (p = 0.548). Comparison with the general population revealed a significantly higher prevalence of hypertension (61.4% vs. 32.2%, p < 0.001) and a lower prevalence of diabetes (1.4% vs. 13.1%, p = 0.001) in the thoracic aneurysm group. Conclusions: The extreme cardiovascular risk associated with abdominal aortic aneurysms is location-specific and not explained by loss of aortic compliance. Thoracic aortic aneurysm, in contrast to abdominal, is not part of the atherosclerotic disease spectrum and, therefore, cardiovascular risk management does not need to be implemented in treatment guidelines of isolated thoracic aneurysms. Hypertension should be treated.

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

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/m2. 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/m2), while 374 (84.6%) had a smaller LA (LAVI: 34.8 [29.2-41.3] ml/m2). 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.

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

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.

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

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 CHA2DS2-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 ß 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).

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.

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.

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

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; P<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 (P<0.001), even after correcting for CAD risk factors (P<0.001). Patients with TAV more often needed concomitant coronary revascularization (OR, 3.50; 95% CI, 2.42-5.06; P<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.

Machine learning methods for perioperative anesthetic management in cardiac surgery patients: a scoping review.

BACKGROUND: Machine learning (ML) is developing fast with promising prospects within medicine and already has several applications in perioperative care. We conducted a scoping review to examine the extent and potential limitations of ML implementation in perioperative anesthetic care, specifically in cardiac surgery patients. METHODS: We mapped the current literature by searching three databases: MEDLINE (Ovid), EMBASE (Ovid), and Cochrane Library. Articles were eligible if they reported on perioperative ML use in the field of cardiac surgery with relevance to anesthetic practices. Data on the applicability of ML and comparability to conventional statistical methods were extracted. RESULTS: Forty-six articles on ML relevant to the work of the anesthesiologist in cardiac surgery were identified. Three main categories emerged: (I) event and risk prediction, (II) hemodynamic monitoring, and (III) automation of echocardiography. Prediction models based on ML tend to behave similarly to conventional statistical methods. Using dynamic hemodynamic or ultrasound data in ML models, however, shifts the potential to promising results. CONCLUSIONS: ML in cardiac surgery is increasingly used in perioperative anesthetic management. The majority is used for prediction purposes similar to conventional clinical scores. Remarkable ML model performances are achieved when using real-time dynamic parameters. However, beneficial clinical outcomes of ML integration have yet to be determined. Nonetheless, the first steps introducing ML in perioperative anesthetic care for cardiac surgery have been taken.

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.

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.

Complications in pulmonary vein isolation in the Netherlands Heart Registration differ with sex and ablation technique.

AIMS: Pulmonary vein isolation (PVI) has become a cornerstone of the invasive treatment of atrial fibrillation. Severe complications are reported in 1-3% of patients. This study aims to compare complications and follow-up outcome of PVI in patients with atrial fibrillation. METHODS AND RESULTS: The data were extracted from the Netherlands Heart Registration. Procedural and follow-up outcomes in patients treated with conventional radiofrequency (C-RF), multielectrode phased RF (Ph-RF), or cryoballoon (CB) ablation from 2012 to 2017 were compared. Subgroup analysis was performed to identify variables associated with complications and repeat ablations. In total, 13 823 patients (69% male) were included. The reported complication incidence was 3.6%. Patients treated with C-RF developed more cardiac tamponades (C-RF 0.8% vs. Ph-RF 0.3% vs. CB 0.3%, P ≤ 0.001) and vascular complications (C-RF 1.7% vs. Ph-RF 1.2% vs. CB 1.3%, P ≤ 0.001). Ph-RF was associated with fewer bleeding complications (C-RF: 1.0% vs. Ph-RF: 0.4% vs. CB: 0.7%, P = 0.020). Phrenic nerve palsy mainly occurred in patients treated with CB (C-RF: 0.1% vs. Ph-RF: 0.2% vs. CB: 1.5%, P ≤ 0.001). In total, 18.4% of patients were referred for repeat ablation within 1 year. Female sex, age, and CHA2DS2-VASc were independent risk factors for cardiac tamponade and bleeding complications, with an adjusted OR for female patients of 2.97 (95% CI 1.98-4.45) and 2.02 (95% CI 1.03-4.00) respectively. CONCLUSION: The reported complication rate during PVI was low. Patients treated with C-RF ablation were more likely to develop cardiac tamponades and vascular complications. Female sex was associated with more cardiac tamponade and bleeding complications.

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

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.

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

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).

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

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.