Expert opinion on design and endpoints for studies on catheter ablation of atrial fibrillation.

INTRODUCTION: Catheter ablation of atrial fibrillation (AF) is frequently studied in randomized trials, observational and registry studies. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of future clinical studies on catheter ablation of AF, implement lessons learned from previous studies, and promote a higher degree of consistency across studies. BACKGROUND: Studies on catheter ablation of AF may benefit from well-described definitions of endpoints and consistent methodology and documentation of outcomes related to efficacy, safety and cost-effectiveness. The availably of new, innovative technologies warrants further consideration about their application and impact on study design and the choice of endpoints. Moreover, recent insights gained from AF ablation studies suggest a reconsideration of some methodological aspects. METHODS: A panel of clinical experts on catheter ablation of AF and designing and conducting clinical studies developed an expert opinion on the design and endpoints for studies on catheter ablation of AF. Discussions within the expert panel with the aim to reach consensus on predefined topics were based on outcomes reported in the literature and experiences from recent clinical trials. RESULTS: A comprehensive set of recommendations is presented. Key elements include the documentation of clinical AF, medication during the study, repeated ablations and their effect on endpoint assessments, postablation blanking and the choice of rhythm-related and other endpoints. CONCLUSION: This expert opinion provides guidance and promotes consistency regarding design of AF catheter ablation studies and identified aspects requiring further research to optimize study design and methodology. CONDENSED ABSTRACT: Recent insights from studies on catheter ablation of atrial fibrillation (AF) and the availability of new innovative technologies warrant reconsideration of methodological aspects related to study design and the choice and assessment of endpoints. This expert opinion, developed by clinical experts on catheter ablation of AF provides a comprehensive set of recommendations related to these methodological aspects. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of clinical studies, implement lessons learned from previous studies, and promote a higher degree of consistency across studies.

Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.

AIMS: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). METHODS AND RESULTS: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. CONCLUSIONS: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF.

Biomarkers predictive of atrial fibrillation in patients with cryptogenic stroke. Insights from the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study.

BACKGROUND AND PURPOSE: There are currently no biomarkers to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF. METHODS: Eligible CS and cryptogenic transient ischaemic attack patients underwent 12-month monitoring with ICMs, clinical follow-up and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n = 74) during monitoring and those without AF (n = 185). Receiver operating characteristic curves were created. Biomarkers reaching area under the receiver operating characteristic curve ≥ 0.7 were dichotomized by finding optimal cut-off values and were used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models. RESULTS: B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase, D-dimer and high-sensitivity cardiac troponin I and T were significantly higher in the AF than non-AF group. BNP and NT-proBNP reached the predefined area under the curve level, 0.755 and 0.725 respectively. Optimal cut-off values were 33.5 ng/l for BNP and 87 ng/l for NT-proBNP. Regression analysis showed that NT-proBNP was a predictor of AF in both unadjusted (odds ratio 7.72, 95% confidence interval 3.16-18.87) and age- and sex-adjusted models (odds ratio 4.82, 95% confidence interval 1.79-12.96). CONCLUSION: Several clinically established biomarkers were associated with AF. NT-proBNP performed best as AF predictor and could be used for selecting patients for long-term monitoring with ICMs.

Time of onset of atrial fibrillation and atrial fibrillation progression data from the RACE V study.

AIMS: Atrial fibrillation (AF) progression is associated with adverse outcome, but the role of the circadian or diurnal pattern of AF onset remains unclear. We aim to assess the association between the time of onset of AF episodes with the clinical phenotype and AF progression in patients with self-terminating AF. METHODS AND RESULTS: The Reappraisal of AF: Interaction Between Hypercoagulability, Electrical Remodelling, and Vascular Destabilization in the Progression of AF study included patients with self-terminating AF who underwent extensive phenotyping at baseline and continuous rhythm monitoring with an implantable loop recorder (ILR). In this subanalysis, ILR data were used to assess the development of AF progression and the diurnal pattern of AF onset: predominant (>80%) nocturnal AF, predominant daytime AF, or mixed AF without a predominant diurnal AF pattern. The median follow-up was 2.2 (1.6-2.8) years. The median age was 66 (59-71) years, and 117 (42%) were women. Predominant nocturnal (n = 40) and daytime (n = 43) AF onset patients had less comorbidities compared to that of mixed (n = 195) AF patients (median 2 vs. 2 vs. 3, respectively, P = 0.012). Diabetes was more common in the mixed group (12% vs. 5% vs. 0%, respectively, P = 0.031), whilst obesity was more frequent in the nocturnal group (38% vs. 12% vs. 27%, respectively, P = 0.028). Progression rates in the nocturnal vs. daytime vs. mixed groups were 5% vs. 5% vs. 24%, respectively (P = 0.013 nocturnal vs. mixed and P = 0.008 daytime vs. mixed group, respectively). CONCLUSION: In self-terminating AF, patients with either predominant nocturnal or daytime onset of AF episodes had less associated comorbidities and less AF progression compared to that of patients with mixed onset of AF. CLINICAL TRIAL REGISTRATION: NCT02726698.

Early diagnosis and better rhythm management to improve outcomes in patients with atrial fibrillation: the 8th AFNET/EHRA consensus conference.

Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.

Dynamic risk assessment to improve quality of care in patients with atrial fibrillation: the 7th AFNET/EHRA Consensus Conference.

AIMS: The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes. METHODS AND RESULTS: This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence. CONCLUSION: The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.

Temporal patterns and short-term progression of paroxysmal atrial fibrillation: data from RACE V.

AIMS: Atrial fibrillation (AF) often starts as a paroxysmal self-terminating arrhythmia. Limited information is available on AF patterns and episode duration of paroxysmal AF. In paroxysmal AF patients, we longitudinally studied the temporal AF patterns, the association with clinical characteristics, and prevalence of AF progression. METHODS AND RESULTS: In this interim analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) registry, 202 patients with paroxysmal AF were followed with continuous rhythm monitoring (implantable loop recorder or pacemaker) for 6 months. Mean age was 64 ± 9 years, 42% were women. Atrial fibrillation history was 2.1 (0.5-4.4) years, CHA2DS2-VASc 1.9 ± 1.3, 101 (50%) had hypertension, 69 (34%) heart failure. One-third had no AF during follow-up. Patients with long episodes (>12 hours) were often men with more comorbidities (heart failure, coronary artery disease, higher left ventricular mass). Patients with higher AF burden (>2.5%) were older with more comorbidities (worse renal function, higher calcium score, thicker intima media thickness). In 179 (89%) patients, 1-year rhythm follow-up was available. On a quarterly basis, average daily AF burden increased from 3.2% to 3.8%, 5.2%, and 6.1%. Compared to the first 6 months, 111 (62%) patients remained stable during the second 6 months, 39 (22%) showed progression to longer AF episodes, 8 (3%) developed persistent AF, and 29 (16%) patients showed AF regression. CONCLUSIONS: In paroxysmal AF, temporal patterns differ suggesting that paroxysmal AF is not one entity. Atrial fibrillation burden is low and determined by number of comorbidities. Atrial fibrillation progression occurred in a substantial number. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier NCT02726698.

Six-beam homodyne laser Doppler vibrometry based on silicon photonics technology.

This paper describes an integrated six-beam homodyne laser Doppler vibrometry (LDV) system based on a silicon-on-insulator (SOI) full platform technology, with on-chip photo-diodes and phase modulators. Electronics and optics are also implemented around the integrated photonic circuit (PIC) to enable a simultaneous six-beam measurement. Measurement of a propagating guided elastic wave in an aluminum plate (speed ≈ 909 m/s @ 61.5 kHz) is demonstrated.

Incidence of atrial fibrillation detected by continuous rhythm monitoring after acute myocardial infarction in patients with preserved left ventricular ejection fraction: results of the ARREST study.

Aims: Cardiac arrhythmias following acute myocardial infarction (AMI) can be associated with major adverse cardiovascular events. Data on the "real incidence" of post-MI arrhythmias are limited. We aimed to determine the rate and burden of cardiac arrhythmias by the use of insertable cardiac monitors (ICM) in patients with preserved left ventricular ejection fraction (LVEF) after AMI. Methods and results: In this prospective observational study, patients with LVEF ≥40% who underwent PCI within 7 days following AMI were enrolled to receive an ICM. Primary outcome was the incidence of new-onset atrial fibrillation (AF) measured by the ICM during a follow-up of 2 years; results: Of 165 consecutive patients with AMI, 50 (30.3%) eligible patients were recruited (mean age 57.8 ± 8.3, 88% male). During follow-up, AF was the most frequently detected arrhythmia. Twenty-nine (58%, 95% CI: 42-70%) patients developed new-onset AF, with a cumulative rate of all detected arrhythmias of 65%. Median time to the first detected AF episode was 4.8 months and the peak cumulative AF burden was detected between 3 and 6 months. Twenty-seven (93%) out of 29 patients with AF were asymptomatic. Cox regression analysis found that baseline troponin level (hazard ratio [HR] for 1 ng/mL increment: 1.03, 95% CI: 1.01-1.06, P = 0.01) and CHA2DS2-VASc score of 4 (HR: 11.42, 95% CI: 1.01-129.06, P = 0.04) were independent risk factors of new-onset AF post-AMI. Conclusion: AF is a frequent but largely underestimated cardiac arrhythmia after AMI. More rigorous monitoring strategies resulting in crucial medical interventions (e.g. implementation of oral anti-coagulation) are needed. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT02492243.

Device-detected atrial fibrillation and risk for stroke: an analysis of >10,000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices).

OBJECTIVE: The aim of this study was to assess the association between maximum daily atrial fibrillation (AF) burden and risk of ischaemic stroke. BACKGROUND: Cardiac implanted electronic devices (CIEDs) enhance detection of AF, providing a comprehensive measure of AF burden. DESIGN, SETTING, AND PATIENTS: A pooled analysis of individual patient data from five prospective studies was performed. Patients without permanent AF, previously implanted with CIEDs, were included if they had at least 3 months of follow-up. A total of 10 016 patients (median age 70 years) met these criteria. The risk of ischaemic stroke associated with pre-specified cut-off points of AF burden (5 min, 1, 6, 12, and 23 h, respectively) was assessed. RESULTS: During a median follow-up of 24 months, 43% of 10 016 patients experienced at least 1 day with at least 5 min of AF burden and for them the median time to the maximum AF burden was 6 months (inter-quartile range: 1.3-14). A Cox regression analysis adjusted for the CHADS2 score and anticoagulants at baseline demonstrated that AF burden was an independent predictor of ischaemic stroke. Among the thresholds of AF burden that we evaluated, 1 h was associated with the highest hazard ratio (HR) for ischaemic stroke, i.e. 2.11 (95% CI: 1.22-3.64, P = 0.008). CONCLUSIONS: Device-detected AF burden is associated with an increased risk of ischaemic stroke in a relatively unselected population of CIEDs patients. This finding may add to the basis for timely and clinically appropriate decision-making on anticoagulation treatment.

Dynamic biomarker profiles in patients with paroxysmal atrial fibrillation: Assessing the differences between sinus rhythm and acute atrial fibrillation episode.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults, yet its underlying pathophysiology remains poorly understood. This study assessed whether circulating biomarker concentrations differ in paroxysmal AF patients during an acute episode compared to sinus rhythm. METHODS: The Time of Calamity study is a prospective biomarker study within the RACE V study. Patients underwent venous blood sampling in sinus rhythm at inclusion in RACE V, as well as during a subsequent acute episode of AF for which patients reported to the hospital. Ten biomarkers were analyzed. RESULTS: Thirty-nine patients (mean age 60 ± 9 years, 10 (25 %) women) were enrolled. During an acute AF episode, dickkopf-related protein 3 and insulin-like growth factor binding protein 7 were significantly lower, while N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitive troponin T (hsTnT), growth differentiation factor 15, and interleukin 6 were significantly higher (all p < 0.05). CONCLUSIONS: Biomarker concentrations in paroxysmal AF patients are dynamic and differ between sinus rhythm and acute AF episodes. Notably, NT-proBNP and hsTnT, commonly used in clinical practice, were significantly elevated during an acute AF episode.

Healthcare utilisation and quality of life according to atrial fibrillation burden, episode frequency and duration.

BACKGROUND: We aimed to evaluate the association between atrial fibrillation (AF) burden, duration and number of episodes with healthcare utilisation and quality of life in patients with early paroxysmal AF without a history of AF. METHODS: In this observational cohort study, we included 417 patients with paroxysmal AF from the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V) Study. Patients were monitored with an insertable cardiac monitor for 1 year. Outcomes collected were healthcare utilisation, and quality of life assessed using the Atrial Fibrillation Severity Scale and EuroQol EQ-5D-5L questionnaires. RESULTS: During 1 year of follow-up, 63 973 AF episodes were detected in 353 (85%) patients. The median AF burden was 0.7% (IQR 0.1-4.0%). AF ablation was performed more frequently in patients with intermediate-to-high AF burdens (>0.2%) (16.2% vs 5.9%, p=0.01) and longer AF episode duration (>1 hour) (15.8% vs 2.0%, p=0.01), whereas cardioversions were more frequent in patients with longer episode duration (>1 hour) (9.5% vs 0%, p=0.04) and intermediate (0.2-1.9%) (but not high) AF burdens (13.6% vs 4.2%, p=0.01). Patients with many episodes (>147) reported higher symptom severity (p=0.001). No differences in symptom severity nor in EQ-5D-5L scores according to AF burden or duration were observed. CONCLUSION: In patients with early paroxysmal AF, higher AF burden and longer episode duration were associated with increased rates of healthcare utilisation but not with symptoms and quality of life. Patients with a higher number of episodes experienced more severe symptoms. TRIAL REGISTRATION NUMBER: NCT02726698.

Clinical Validation of Carotid-Femoral Pulse Wave Velocity Measurement Using a Multi-Beam Laser Vibrometer: The CARDIS Study.

BACKGROUND: Carotid-femoral pulse wave velocity (cfPWV) is the gold standard for noninvasive arterial stiffness assessment, an independent predictor of cardiovascular disease, and a potential parameter to guide therapy. However, cfPWV is not routinely measured in clinical practice due to the unavailability of a low-cost, operator-friendly, and independent device. The current study validated a novel laser Doppler vibrometry (LDV)-based measurement of cfPWV against the reference technique. METHODS: In 100 (50 men) hypertensive patients, cfPWV was measured using applanation tonometry (Sphygmocor) and the novel LDV device. This device has 2 handpieces with 6 laser beams each that simultaneously measure vibrations from the skin surface at carotid and femoral sites. Pulse wave velocity is calculated using ECG for the identification of cardiac cycles. An ECG-independent method was also devised. Cardiovascular risk score was calculated for patients between 40 and 75 years old using the WHO risk scoring chart. RESULTS: LDV-based cfPWV correlated significantly with tonometry (r=0.86, P<0.0001 ECG-dependent [cfPWVLDV_ECG] and r=0.80, P<0.001 ECG-independent [cfPWVLDV_w/oECG] methods). Bland-Altman analysis showed nonsignificant bias (0.65 m/s) and acceptable SD (1.27 m/s) between methods. Intraobserver coefficient of variance for LDV was 4.7% (95% CI, 3.0%-5.5%), and interobserver coefficient of variance was 5.87%. CfPWV correlated significantly with CVD risk (r=0.64, P<0.001; r=0.41, P=0.003; and r=0.37, P=0.006 for tonometry, LDV-with, and LDV-without ECG, respectively). CONCLUSIONS: The study demonstrates clinical validity of the LDV device. The LDV provides a simple, noninvasive, operator-independent method to measure cfPWV for assessing arterial stiffness, comparable to the standard existing techniques. REGISTRATION: URL: https://clinicaltrials.gov/study/NCT03446430; Unique identifier: NCT03446430.

Heart rate characteristic based modelling of atrial fibrillatory rate using implanted cardiac monitor data.

Objective. The objective of the present study is to investigate the feasibility of using heart rate characteristics to estimate atrial fibrillatory rate (AFR) in a cohort of atrial fibrillation (AF) patients continuously monitored with an implantable cardiac monitor. We will use a mixed model approach to investigate population effect and patient specific effects of heart rate characteristics on AFR, and will correct for the effect of previous ablations, episode duration, and onset date and time.Approach. The f-wave signals, from which AFR is estimated, were extracted using a QRST cancellation process of the AF episodes in a cohort of 99 patients (67% male; 57 ± 12 years) monitored for 9.2(0.2-24.3) months as median(min-max). The AFR from 2453 f-wave signals included in the analysis was estimated using a model-based approach. The association between AFR and heart rate characteristics, prior ablations, and episode-related features were modelled using fixed-effect and mixed-effect modelling approaches.Main results. The mixed-effect models had a better fit to the data than fixed-effect models showing h.c. of determination (R2 = 0.49 versusR2 = 0.04) when relating the variations of AFR to the heart rate features. However, when correcting for the other factors, the mixed-effect model showed the best fit (R2 = 0.04). AFR was found to be significantly affected by previous catheter ablations (p< 0.05), episode duration (p< 0.05), and irregularity of theRRinterval series (p< 0.05).Significance. Mixed-effect models are more suitable for AFR modelling. AFR was shown to be faster in episodes with longer duration, less organizedRRintervals and after several ablation procedures.

Brady- and tachyarrhythmias detected by continuous rhythm monitoring in paroxysmal atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) is associated with adverse events including conduction disturbances, ventricular arrhythmias and sudden death. The aim of this study was to examine brady- and tachyarrhythmias using continuous rhythm monitoring in patients with paroxysmal self-terminating AF (PAF). METHODS: In this multicentre observational substudy to the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V), we included 392 patients with PAF and at least 2 years of continuous rhythm monitoring. All patients received an implantable loop recorder, and all detected episodes of tachycardia ≥182 beats per minute (BPM), bradycardia ≤30 BPM or pauses ≥5 s were adjudicated by three physicians. RESULTS: Over 1272 patient-years of continuous rhythm monitoring, we adjudicated 1940 episodes in 175 patients (45%): 106 (27%) patients experienced rapid AF or atrial flutter (AFL), pauses ≥5 s or bradycardias ≤30 BPM occurred in 47 (12%) patients and in 22 (6%) patients, we observed both episode types. No sustained ventricular tachycardias occurred. In the multivariable analysis, age >70 years (HR 2.3, 95% CI 1.4 to 3.9), longer PR interval (HR 1.9, 1.1-3.1), CHA2DS2-VASc score ≥2 (HR 2.2, 1.1-4.5) and treatment with verapamil or diltiazem (HR 0.4, 0.2-1.0) were significantly associated with bradyarrhythmia episodes. Age >70 years was associated with lower rates of tachyarrhythmias. CONCLUSIONS: In a cohort exclusive to patients with PAF, almost half experienced severe bradyarrhythmias or AF/AFL with rapid ventricular rates. Our data highlight a higher than anticipated bradyarrhythmia risk in PAF. TRIAL REGISTRATION NUMBER: NCT02726698.

Women have less progression of paroxysmal atrial fibrillation: data from the RACE V study.

BACKGROUND: Sex differences in atrial fibrillation (AF) are observed in terms of comorbidities, symptoms, therapies received, AF progression and cardiovascular complications. METHODS: We assessed the differences in prevalence and the determinants of AF progression, as well as the clinical characteristics and quality of life (QoL), between women and men with paroxysmal AF included in the RACE V (Reappraisal of Atrial Fibrillation: Interaction between hyperCoagulability, Electrical remodeling, and Vascular Destabilisation in the Progression of AF) study. At baseline, extensive phenotyping was done. To assess AF progression, implantable loop recorder (ILR) monitoring was used throughout follow-up. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of paroxysmal AF (>3% burden increase). RESULTS: 417 patients were included, 179 (43%) of whom were women. Women were older (median 67 years vs 63 years, p<0.001), less often had coronary artery disease (n=11 (6%) vs n=36 (16%), p=0.003), had more obesity (n=57 (32%) vs n=50 (21%), p=0.013), had less epicardial and pericardial fat (median 144 (interquartile range [IQR] 94-191) mL vs 199 (IQR 146-248) mL, p<0.001; and median 89 (ICQ 61-121) mL vs 105 (IQR 83-133) mL, p<0.001, respectively) and had more impaired left atrial function. The median follow-up was 2.2 (1.6-2.8) years. 51 of 417 patients (5.5% per year) showed AF progression (15/179 (8.4%) women and 36/238 (15.1%) men, p=0.032). Multivariable analysis showed tissue factor pathway inhibitor, N-terminal prohormone brain natriuretic peptide (NT-proBNP) and PR interval being associated with AF progression in women and factor XIIa:C1 esterase, NT-proBNP and proprotein convertase subtilisin/kexin type 9 in men. QoL was not different between sexes. CONCLUSION: Despite older age, the incidence of AF progression was lower in women. Parameters associated with AF progression varied in part between sexes, suggesting different underlying pathophysiological mechanisms.

Analysis of atrial fibrillatory rate during spontaneous episodes of atrial fibrillation in humans using implantable loop recorder electrocardiogram.

Atrial fibrillatory rate (AFR) can predict outcome of interventions for atrial fibrillation (AF); however, AFR behavior at AF onset in humans is poorly described. We studied AFR during spontaneous AF episodes in patients with lone paroxysmal AF who received implantable loop recorders and had AF episodes of 1 hour or more recorded (n = 4). Mean AFR per minute was assessed from continuous implantable loop recorder electrocardiogram using spatiotemporal QRST cancellation and time-frequency analysis. Atrial fibrillatory rate increased from 290 ± 20 to 326 ± 39 fibrillations per minute during the first 3 hours (P<.05) and reached plateau then. Atrial fibrillatory rate beyond the initial 3 hours can, therefore, be considered stable and may be evaluated for prediction of intervention effect.

Prevalence and determinants of atrial fibrillation progression in paroxysmal atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) often progresses from paroxysmal AF (PAF) to more permanent forms. To improve personalised medicine, we aim to develop a new AF progression risk prediction model in patients with PAF. METHODS: In this interim-analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF study, patients with PAF undergoing extensive phenotyping at baseline and continuous rhythm monitoring during follow-up of ≥1 year were analysed. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of PAF with >3% burden increase. Multivariable analysis was done to identify predictors of AF progression. RESULTS: Mean age was 65 (58-71) years, 179 (43%) were female. Follow-up was 2.2 (1.6-2.8) years, 51 of 417 patients (5.5%/year) showed AF progression. Multivariable analysis identified, PR interval, impaired left atrial function, mitral valve regurgitation and waist circumference to be associated with AF progression. Adding blood biomarkers improved the model (C-statistic from 0.709 to 0.830) and showed male sex, lower levels of factor XIIa:C1-esterase inhibitor and tissue factor pathway inhibitor, and higher levels of N-terminal pro-brain natriuretic peptide, proprotein convertase subtilisin/kexin type 9 and peptidoglycan recognition protein 1 were associated with AF progression. CONCLUSION: In patients with PAF, AF progression occurred in 5.5%/year. Predictors for progression included markers for atrial remodelling, sex, mitral valve regurgitation, waist circumference and biomarkers associated with coagulation, inflammation, cardiomyocyte stretch and atherosclerosis. These prediction models may help to determine risk of AF progression and treatment targets, but validation is needed. TRIAL REGISTRATION NUMBER: NCT02726698.

Sudden death during follow-up after new-onset ventricular tachycardia in vascular surgery patients.

BACKGROUND: Vascular surgery patients are at increased risk for late sudden cardiac death. Identification of patients at risk during surgery offers the opportunity for focused therapy. METHODS: We monitored 483 vascular surgery patients who had no documented history of arrhythmias to identify perioperative new-onset ventricular tachyarrhythmia (VT) and myocardial ischemia using a continuous electrocardiographic (ECG) device for 72 hours. Cardiac risk factors, left ventricular ejection fraction (LVEF), medical therapy, inflammation status, and perioperative ischemia in relation to arrhythmia were noted in all patients. During follow-up, event-based outcomes analysis was used to describe survival. RESULTS: New-onset perioperative VT was detected in 33 patients (6.8%). A higher percentage of patients experiencing perioperative VT had reduced LVEF preoperatively than those without VT (24% vs 12%; P = .04). Additionally, fewer patients experiencing VT were receiving statins than those without (70% vs 85%; P = .02). Patients experiencing VT had a higher incidence of myocardial ischemia (30% vs 18%; P = .10). Perioperative VT was preceded by ischemia in only 60% of the cases. The overall cohort survival was 83% at 24-month follow-up (interquartile range [IQR], 1.1-1.3). Sudden cardiac death free survival among patients experiencing VT was less than in those without (79% vs 92%; P = .02). After adjusting for gender, cardiac risk factors, and type of surgery, new-onset perioperative VT was associated with sudden cardiac death (hazard ratio [HR], 2.6; 95% confidence interval [CI], 1.1-5.8). CONCLUSION: Perioperative VT is likely to be associated with late sudden cardiac death and decreased survival. Continuous perioperative ECG is an effective method to identify VT and may allow improved management of these patients.

Heart Rate Variability and Clinical Features as Predictors of Atrial Fibrillation Recurrence After Catheter Ablation: A Pilot Study.

Single-procedure catheter ablation success rate is as low as 52% in atrial fibrillation (AF) patients. This study evaluated the feasibility of using clinical data and heart rate variability (HRV) features extracted from an implantable cardiac monitor (ICM) to predict recurrences in patients prior to undergoing catheter ablation for AF. HRV-derived features were extracted from the 500 beats preceding the AF onset and from the first 2 min of the last AF episode recorded by an ICM of 74 patients (67% male; 57 ± 12 years; 26% non-paroxysmal AF; 57% AF recurrence) before undergoing their first AF catheter ablation. Two types of classification algorithm were studied to predict AF recurrence: single classifiers including support vector machines, classification and regression trees, and K-nearest neighbor classifiers as well as ensemble classifiers. The sequential forward floating search algorithm was used to select the optimum feature set for each classification method. The optimum weighted voting method, which used an optimum combination of the single classifiers, was the best overall classifier (accuracy = 0.82, sensitivity = 0.76, and specificity = 0.87). Clinical and HRV features can be used to predict rhythm outcome using an ensemble classifier which would enable a more effective pre-ablation patient triage that could reduce the economic and personal burden of the procedure by increasing the success rate of first catheter ablation.