The prognostic value of systemic vascular resistance in heart failure patients with permanent atrial fibrillation: a retrospective study.

Heart failure (HF) and permanent atrial fibrillation (AF) interact mutually, exacerbating hemodynamic effects and causing adverse outcomes and increased healthcare costs. Monitoring hemodynamic indicators in patients with these comorbidities is crucial for effective clinical management. Transthoracic impedance cardiography (ICG) has been widely employed in assessing hemodynamic status in clinical settings. Given the limited research on the prognostic significance of ICG parameters in HF with permanent AF, we undertook this study. A total of 66 HF patients with permanent AF were included in this retrospective study, and the primary outcome was rehospitalization due to worsening HF within 180-day post-discharge. Cox regression analysis was performed to explore the connection between ICG-evaluated parameters and the outcome risk. Receiver operating characteristic (ROC) curve analysis determined the optimal cutoff values of risk factors, subsequently applied in plotting Kaplan Meier (KM) survival curves. Multivariate Cox regression analysis revealed that systemic vascular resistance (SVR) both on admission and at discharge independently predicted rehospitalization for worsening HF. ROC analysis established optimal SVR cutoff values: 320.89 (kPa s/L) on admission and 169.94 (kPa s/L) at discharge (sensitivity 70%, specificity 94.4%, area under the curve (AUC) 0.831, respectively, sensitivity 90%, specificity 55.6%, AUC 0.742). KM survival curves analysis showed that patients with SVR > 320.89 (kPa s/L) on admission had an 8.14-fold (P < 0.001) increased risk of the end-point event compared with those with SVR ≤ 320.89 (kPa s/L). Similarly, patients with SVR > 169.94 (kPa s/L) at discharge faced a risk elevated by 6.57 times (P = 0.002) relative to those with SVR ≤ 169.94 (kPa s/L). In HF patients with permanent AF, SVR measured by ICG emerges as an independent risk factor and clinical predictor for HF deterioration-related readmission within 180 days after discharge. Higher SVR levels, both upon admission and at discharge, correlate with an incremental rehospitalization risk.

Association between T-tau protein and Aß42 in plasma neuronal-derived exosomes and cognitive impairment in patients with permanent atrial fibrillation and the role of anticoagulant therapy and inflammatory mechanisms.

BACKGROUND: This study explores whether the differences in cognitive performance among individuals with permanent atrial fibrillation (AF) are attributable to the duration of AF and anticoagulant therapy and explores the possible inflammatory mechanism of cognitive dysfunction related to AF. METHODS: A total of 260 patients aged 50-75 years without previous cerebrovascular events were enrolled in this study. These 260 patients had been divided into the AF group (140 patients) and sinus rhythm group (120 patients). In the AF group, we divided participants into cognitive impairment (CI) group (90 patients) and cognitive normal (CN) group (50 patients). In the sinus rhythm group, we also divided participants into CI group (61 patients) and CN group (59 patients). The Mini-Mental State Examination (MMSE) was used to assess the cognitive function of all participants. Neuronal-derived exosomes were enriched in peripheral blood by immunoprecipitation and were confirmed by a transmission electron microscope, nanoparticle tracking analysis, and western blot. Alzheimer's disease-pathogenic exosomal proteins and inflammatory cytokines were quantified. The association between AF and cognitive function was estimated by logistic regression analysis. ANOVA or Welch's t-test compared the difference in protein concentrations between groups. RESULTS: Non-anticoagulant therapy in patients with AF was significantly associated with CI (OR = 13.99, 95% CI: 2.67-73.36, p < .01). The incidence of dementia in patients with AF > 3 years was significantly higher than in patients with AF ≤ 3 years, but there was no significant difference in total cognitive dysfunction (mild cognitive impairment [MCI] + dementia) (p = .126). The adjusted exosome concentrations of T-tau and amyloid-ß protein 42 (Aß42) in the CI group were significantly higher than in the CN group (p < .001). The serum concentrations of IL-6 and matrix metalloproteinase-9 (MMP-9) in patients with AF were higher than those in patients with sinus rhythm (p < .001). CONCLUSION: Aß42 and T-tau in peripheral blood neuronal-derived exosomes maybe be associated with the early diagnosis of CI in patients with permanent AF. However, the value of Aß42 and T-tau for CI in patients with permanent AF still needs to be confirmed in future randomized control trials.

Persistent or permanent atrial fibrillation is associated with severe cardioembolic stroke in patients with non-valvular atrial fibrillation.

BACKGROUND: Little is known about the difference in the severity of cardioembolic (CE) stroke between patients with paroxysmal atrial fibrillation (PAF) and persistent/permanent AF (PerAF). We assessed stroke severity in patients with CE stroke divided by the type of AF. METHODS: Three hundred and fifty-eight consecutive patients with CE stroke within 48 h of onset and with a modified Rankin Scale (mRS) score ≤ 1 before onset were studied. We compared basic characteristics, stroke severity, and functional outcome between patients with PAF (n = 127) and PerAF (n = 231). RESULTS: Patients with PerAF were more likely to take oral anticoagulants (OACs) than those with PAF (37% vs. 13%, P <  0.0001), even though still underuse of OAC in both patients. Regarding stroke severity on admission, patients with PerAF exhibited a tendency toward a higher score on the National Institutes of Health Stroke Scale (NIHSS) compared with patients with PAF (12 [5-20] vs. 9 [4-18]; P = 0.12). Mortality and mRS score at discharge were higher in the PerAF than in the PAF group (13% vs. 4%; P = 0.005, and 3 [1-5] vs. 2 [1-4]; P = 0.01, respectively). Multivariate analyses confirmed that PerAF was a significant determinant of severe stroke (NIHSS score > 8) on admission (odds ratio [OR] to PAF = 1.80; 95% confidence interval [CI] 1.08-2.98; P = 0.02) and of an mRS score ≥ 3 at discharge (OR = 2.07; 95% CI 1.24-3.46; P = 0.006). Patients with PerAF had three times more internal carotid artery occlusion evaluated by magnetic resonance angiography, which indicated a more severe cerebral embolism compared with patients with PAF. CONCLUSIONS: We found underuse of OAC in high risk AF patients with CE stroke. PerAF is significantly associated with severe stroke on admission and an unfavorable functional outcome at discharge in Japanese patients with CE stroke.

Short-period temporal repolarization dispersion in subjects with atrial fibrillation and decompensated heart failure.

BACKGROUND/OBJECTIVES: The association between chronic heart failure (CHF) and permanent atrial fibrillation is very frequent. The repolarization duration was already found predictive for atrial fibrillation. Aim of this study was to evaluate the influence of atrial fibrillation on short period repolarization variables in decompensated CHF patients. METHOD: We used 5 min ECG recordings to assess the mean, standard deviation (SD), and normalized variance (NV) of the following variables: QT end (QTe), QT peak (QTp), and T peak to T end (Te) in 121 decompensated CHF, of whom 40 had permanent atrial fibrillation, too. We reported also the 30-day mortality. RESULTS: QTpSD (p < .01), TeSD (p < .01), QTpVN (p < .01), and TeVN (p < .01) were higher in the atrial fibrillation than among sinus rhythm CHF subjects. Multivariable logistic analysis selected only TeSD (odd ratio, o.r.: 1.32, 95% confidence interval, c.i.: 1.06-1.65, p: .015) associated with atrial fibrillation. A total of 27 patients died during the 30-days follow-up (overall mortality rate 22%), 7 (18%), and 20 (25%) respectively in the atrial fibrillation and sinus rhythm patients. Furthermore, the following variables were associated to the morality risk: NT-pro Brain Natriuretic Peptide (o.r.: 1.00, 95% c.i.: 1.00-1.00, p: .041), left ventricular end diastolic diameter (o.r.: 0.81, 95% c.i.: 0.67-0.96, p: .010), and Te mean (o.r.: 1.04, 95% c.i.: 1.02-1.09, p: .012). CONCLUSION: In decompensated CHF subjects, Te mean seems be associated to mortality and TeSD to the permanent atrial fibrillation. We could hypothesize that, during severe CHF, the multi-level ionic CHF channel derangement could be critical in influencing these non-invasive markers. (ClinicalTrials.gov number, NCT04127162).

The Benefit of Atrioventricular Junction Ablation for Permanent Atrial Fibrillation and Heart Failure Patients Receiving Cardiac Resynchronization Therapy: An Updated Systematic Review and Meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is correlated with a poor biventricular pacing and inadequate response to cardiac resynchronization therapy (CRT). Biventricular pacing improvement can be achieved by conducting the atrioventricular junction ablation (AVJA). We aimed to investigate the benefit of AVJA for permanent AF and heart failure with reduced ejection fraction (HFrEF) patients receiving CRT. METHODS: In August 2020, a systematic review and meta-analysis study comparing CRT plus AVJA versus CRT for permanent AF and HFrEF patients was conducted. Relevant articles were identified through the electronic scientific database such as ClinicalTrials.gov, ProQuest, ScienceDirect, PubMed, and Cochrane. The pooled risk ratio (RR) and pooled mean difference (MD) were estimated. RESULTS: A total of 3199 patients from 14 cohort studies were involved in this study. Additional AVJA reduced cardiovascular mortality (RR = 0.75, 95% confidence interval [CI] = 0.61 to 0.93, P < 0.01) in permanent AF and HFrEF patients receiving CRT. Biventricular pacing rate was higher in CRT plus AVJA group (MD = 8.65%, 95% CI = 5.62 to 11.67, P < 0.01) than in CRT alone group. The reverse remodeling characterized by the reduction of left ventricular end-diastolic diameter (LVEDD) was greater in the CRT plus AVJA group (MD = -2.11 mm, 95% CI = -3.79 to -0.42, P = 0.01). CONCLUSION: In permanent AF and HFrEF patients receiving CRT, AVJA effectively increased the biventricular pacing rate. Adequate biventricular pacing rate provided a better response to the CRT marked by the greater ventricular reverse remodeling and survival from cardiovascular mortality.

Sex-related differences in risk factors, outcome, and quality of life in patients with permanent atrial fibrillation: results from the RACE II study.

AIMS: Atrial fibrillation (AF) risk factors translate into disease progression. Whether this affects women and men differently is unclear. We aimed to investigate sex differences in risk factors, outcome, and quality of life (QoL) in permanent AF patients. METHODS AND RESULTS: The Rate Control Efficacy in Permanent Atrial Fibrillation (RACE II) randomized 614 patients, 211 women and 403 men, to lenient or strict rate control. In this post hoc analysis risk factors, cardiovascular events during 3-year follow-up (cardiovascular death, heart failure hospitalization, stroke, systemic embolism, bleeding, and life-threatening arrhythmic events), outcome parameters, and QoL were compared between the sexes. Women were older (71 ± 7 vs. 66 ± 8 years, P < 0.001), had more hypertension (70 vs. 57%, P = 0.002), and heart failure with preserved ejection fraction (36 vs. 17%, P < 0.001), but less coronary artery disease (13 vs. 21%, P = 0.02). Women had more risk factors (3.7 ± 1.2 vs. 2.9 ± 1.4, P < 0.001) Cardiovascular events occurred in 46 (22%) women and 59 (15%) men (P = 0.03). Women had a 1.52 times [95% confidence interval (CI) 1.03-2.24] higher yearly cardiovascular event-rate [8.2% (6.0-10.9) vs. 5.4% (4.1-6.9), P = 0.03], but this was no longer significant after adjusting for the number of underlying risk factors. Women had reduced QoL, irrespective of age and heart rate but negatively influenced by their risk factors. CONCLUSION: In this permanent AF population, women had more accumulation of AF risk factors than men. The observed higher cardiovascular event rate in women was no longer significant after adjusting for the number of risk factors. Further, QoL was negatively influenced by the higher number of risk factors in women. This suggests that sex differences may be driven by the greater risk factor burden in women.

Influence of heart rate control on exercise capacity and quality of life in patients with permanent atrial fibrillation.

BACKGROUND: The optimal level of heart rate (HR) control in patients with atrial fibrillation (AF) is unknown. To assess the effect of rate control on cardiopulmonary exercise capacity and quality of life (QoL) in permanent AF. METHODS: One hundred forty-three patients with permanent AF were enrolled in this study. All patients received rate control medications and were followed up for 1 year. After 1-year therapy, the exercise capacity and QoL were evaluated by cardiopulmonary exercise testing (CPET) and 36-item Short-Form Health Survey, respectively. Data were compared by dividing the patients according to the following criteria: (1) whether the resting HR was ≤80 or > 80 bpm; (2) whether the exercise HR during moderate exercises on CPET was ≤110 or > 110 bpm; and (3) whether the resting HR was ≤80 bpm and exercise HR was ≤110 bpm. RESULTS: No significant differences in peak oxygen uptake, peak metabolic equivalent, and anaerobic threshold were found between the strict control and lenient control groups. Both physical component summary (PCS) and mental component summary (MCS) were significantly higher for the strict rate control group than for the lenient control group. The single-factor correlation analysis revealed a negative correlation between resting HR and both PCS and MCS. The multivariable linear regression analysis indicated that both exercise HR and duration of AF linearly correlated with PCS and MCS. CONCLUSIONS: Therefore, in patients with permanent AF, exercise capacity may not be affected by the stringency of rate control, and strict rate control may be associated with better QoL.

His-bundle pacing as a standard approach in patients with permanent atrial fibrillation and bradycardia.

BACKGROUND: His-bundle (HB) pacing is the most physiological method of ventricular pacing. However, it is also considered a demanding procedure with a low success rate and has suboptimal pacing parameters. There is a scarcity of data concerning HB pacing as a standard approach in patients with symptomatic bradycardia. Our goal was to compare acute and chronic results of two approaches to pacing in patients with permanent atrial fibrillation, narrow QRS complexes, and symptomatic bradycardia: right ventricular myocardial pacing versus HB pacing. METHODS: Consecutive patients who received HB pacemakers were compared with historical controls-i.e., consecutive patients with classic VVI pacemaker implantations, performed by the same operator before 2014 (commencement of routine HB implantations). Acute and long-term capture threshold, sensing, battery current drain, as well as procedure and fluoroscopy duration, complications, and success rate were compared. RESULTS: One hundred and twenty-five patients were analyzed (including 65 patients with HB pacing): age 73.0 ± 10.5 years, left ventricular ejection fraction of 48.2 ± 13.5%. HB pacing was inferior to right ventricular myocardial pacing in terms of higher threshold, lower sensing amplitude, higher current drain, lower success rate, longer procedure, and fluoroscopy times. However, despite this, HB procedure and fluoroscopy times of 64.4 ± 30.0 and 11.0 ± 10.7 minutes, respectively, long-term successful HB pacing in 87.9% of patients, a chronic threshold of 1.5 ± 1.1 V, chronic sensing of 3.6 ± 2.5 mV, and chronic current drain per pulse of 3.4 ± 4.4 µAh seem acceptable. CONCLUSIONS: HB pacing can be used as an alternative standard method of pacing in atrial fibrillation patients.

Negative outcomes associated with medication in patients with chronic atrial fibrillation who present at the emergency department.

WHAT IS KNOWN AND OBJECTIVE: Medication is the main treatment option for patients with chronic atrial fibrillation. However, medication can have negative effects. We aimed to detect negative outcomes associated with medication that led to patients with chronic atrial fibrillation presenting themselves to hospital emergency departments. We assessed the severity of those outcomes and comment on whether they could have been avoided. METHODS: This descriptive, cross-sectional study included all patients with chronic atrial fibrillation who attended the emergency department of our tertiary hospital. We used the Dader method to identify and evaluate the negative outcomes associated with medication through interviews with patients and scrutiny of the clinical charts. RESULTS AND DISCUSSION: Of the 198 eligible patients who presented at the emergency department, 134 (67·7%) did so because of negative outcomes associated with medication (41% related to necessity, 32·1% to effectiveness and 26·9% to safety); 67·9% of those negative outcomes could have been avoided. In terms of severity, 6·7% were mild, 31·3% moderate, 51·5% severe and 10·4% fatal. The Anatomical Therapeutic Chemical Classification anatomical group most frequently associated with negative outcomes was the cardiovascular system, followed by blood/blood-forming organs. WHAT IS NEW AND CONCLUSION: A high percentage of patients with chronic atrial fibrillation presenting at hospital emergency departments had negative outcomes associated with medication. Some led to deaths. More than half of these were severe, and most could have been avoided.

Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation: results from the ARISTOTLE trial.

AIMS: It is uncertain whether the benefit from apixaban varies by type and duration of atrial fibrillation (AF). METHODS AND RESULTS: A total of 18 201 patients with AF [2786 (15.3%) with paroxysmal and 15 412 (84.7%) with persistent or permanent] were randomized to apixaban or warfarin. In this pre-specified secondary analysis, we compared outcomes and treatment effect of apixaban vs. warfarin by AF type and duration. The primary efficacy endpoint was a composite of ischaemic or haemorrhagic stroke or systemic embolism. The secondary efficacy endpoint was all-cause mortality. There was a consistent reduction in stroke or systemic embolism (P for interaction = 0.71), all-cause mortality (P for interaction = 0.75), and major bleeding (P for interaction = 0.50) with apixaban compared with warfarin for both AF types. Apixaban was superior to warfarin in all studied endpoints, regardless of AF duration at study entry (P for all interactions >0.13). The rate of stroke or systemic embolism was significantly higher in patients with persistent or permanent AF than patients with paroxysmal AF (1.52 vs. 0.98%; P = 0.003, adjusted P = 0.015). There was also a trend towards higher mortality in patients with persistent or permanent AF (3.90 vs. 2.81%; P = 0.0002, adjusted P = 0.066). CONCLUSION: The risks of stroke, mortality, and major bleeding were lower with apixaban than warfarin regardless of AF type and duration. Although the risk of stroke or systemic embolism was lower in paroxysmal than persistent or permanent AF, apixaban is an attractive alternative to warfarin in patients with AF and at least one other risk factor for stroke, regardless of the type or duration of AF.

The ratio of cytochrome c oxidase subunit 4 isoform 4I1 and 4I2 mRNA is changed in permanent atrial fibrillation.

AIMS: The conditions of hypoxia are suggested to induce permanent atrial fibrillation (AF). The regulation of COX4I2 and COX4I1 depends on oxygen availability in tissues. A role of COX4I2 in the myocardium of AF patients is supposed for pathogenesis of AF and subsequent alterations in the electron transfer chain (ETC) under hypoxia. METHODS AND RESULTS: In vitro, influence of hypoxia on HeLa 53 cells was studied and elevated parts of COX 4I2 were confirmed. Myocardial biopsies were taken ex vivo from the patients' Right Atria with SR (n = 31) and AF (n = 11), respectively. RT- PCR for mRNA expresson, mitochondrial respiration by polarography and the protein content of cytochrome c oxidase (CytOx) subunit 4I1 and CytOx subunit 4I2 by ELISA were studied. Clinical data were correlated to the findings of gene expressions in parallel. Patients with permanent AF had a change in isoform 4I2/4I1 expression along with a decrease of isoform COX 4I1 expression. The 4I2/4I1 ratio of mRNA expression was increased from 0.630 to 1.058 in comparison. However, the protein content of CytOx subunit 4 was much lower in the AF group, whereas the respiration/units enzyme activity in both groups remained the same. CONCLUSIONS: This study describes a possible molecular correlate for the development of AF. Due to the known functional significance of COX 4I2, mitochondrial dysfunction can be assumed as a part of the pathogenesis of AF.

A leadless pacemaker implantation for a patient with systemic right ventricle under ventricular assist device support.

Patients with congenitally corrected transposition of the great arteries (ccTGA) often develop complete atrioventricular block and heart failure due to the abnormal disposition of atrioventricular node and disadvantage of systemic right ventricle. These issues are managed with a pacing system and a ventricular assist device (VAD), respectively. While technological advances offer new treatment strategies, the simultaneous deployment of a leadless pacemaker and a VAD in cases of ccTGA remains unexplored. Here, we present a case of leadless pacemaker implantation for a VAD-supported ccTGA patient. The safety of a leadless pacemaker for a subpulmonary left ventricle and electromagnetic interference between devices are major concerns when implanting a leadless pacemaker; however, the current case overcomes these obstacles. There were no perioperative complications, and both devices were functioning without problems during a one-year follow up. We expect that, even in patients with cardiac complexity such as systemic right ventricle under VAD support, a leadless pacemaker could become the treatment of choice if the indication is appropriate, although careful and close follow up is needed. Learning objective: Technological advances expand treatment strategies and provide significant benefits to patients with adult congenital heart disease (ACHD). However, discussion of the combination of a leadless pacemaker and a ventricular assist device (VAD) is rare. We demonstrated the efficacy of a leadless pacemaker for a subpulmonary left ventricle in a patient with systemic right ventricle on VAD. This approach could be an option even for ACHD patients.

Left Atrial Appendage Closure Device Embolization under the Anterior Leaflet of Mitral Valve: Echocardiographic Diagnosis and Management.

A 76-year-old man with history of previous coronary artery bypass grafting, permanent atrial fibrillation in novel oral anticoagulation therapy, and gastrointestinal bleedings underwent percutaneous left atrial appendage closure. The procedure was complicated by intraoperative device embolization, which caused a dynamic obstruction of the left ventricular outflow tract leading to severe hemodynamic instability. Transesophageal echocardiography showed a device in the ventricle site of the mitral anterior leaflet. The coronary angiography showed also patency of both arterial grafts in stable coronary artery disease. After failing the percutaneous retrieval with a snare, emergent surgery was planned. A moderate calcified aortic valve stenosis was also found, but in consideration of the unstable clinical conditions of the patient, we thought of performing a transcatheter aortic valve replacement (TAVR) in a second time. We have carefully planned the surgical retrieval of the device embolized paying attention of his several comorbidities. The strategy to remove the device with cardiopulmonary bypass without cross-clamping the aorta through a right mini-thoracotomy has been preferred.

Ivabradine for controlling heart rate in permanent atrial fibrillation: A translational clinical trial.

BACKGROUND: Pharmacological options for rate control in atrial fibrillation are scarce. Ivabradine was postulated to reduce the ventricular rate in this setting. OBJECTIVES: The objectives of this study were to evaluate the mechanism of inhibition of atrioventricular conduction produced by ivabradine and to determine its efficacy and safety in atrial fibrillation. METHODS: The effects of ivabradine on atrioventricular node and ventricular cells were studied by in vitro whole-cell patch-clamp experiments and mathematical simulation of human action potentials. In parallel, a multicenter, randomized, open-label, phase III clinical trial compared ivabradine with digoxin for uncontrolled permanent atrial fibrillation despite ß-blocker or calcium channel blocker treatment. RESULTS: Ivabradine 1 µM inhibited "funny" current and rapidly activating delayed rectifier potassium channel current by 28.9% and 22.8%, respectively (P < .05). The sodium channel current and L-type calcium channel current were reduced only at 10 µM. Ivabradine slowed the firing frequency of a modeled human atrioventricular node action potential by 10.6% and induced a minimal prolongation of ventricular action potential. Thirty-five (51.5%) patients were randomized to ivabradine and 33 (49.5%) to digoxin. The mean daytime heart rate decreased by 11.6 beats/min (-11.5%) in the ivabradine arm (P = .02) vs 19.6 (-20.6%) in the digoxin arm (P < .001), although the noninferiority margin of efficacy was not met (Z = -1.95; P = .97). The primary safety end point occurred in 3 patients (8.6%) on ivabradine and in 8 (24.2%) on digoxin (P = .10). CONCLUSION: Ivabradine produced a moderate rate reduction in patients with permanent atrial fibrillation. The inhibition of funny current in the atrioventricular node seems to be the main mechanism responsible for this reduction. Compared with digoxin, ivabradine was less effective, was better tolerated, and had a similar rate of serious adverse events.

Postoperative atrial fibrillation in mitral valve surgery is not benign.

OBJECTIVE: Postoperative atrial fibrillation (POAF) is common after cardiac surgery and is often considered to be benign despite recent data suggesting worse outcomes. There are no guidelines for the amount of POAF that triggers anticoagulation or for postoperative surveillance. We examined the rate of POAF, incidence of neurologic events, development of permanent atrial fibrillation, and mortality in patients undergoing isolated mitral valve surgery at a Mitral Foundation reference center. METHODS: This is a retrospective cohort study of 922 adult patients from 2011 to 2022 with no preoperative history of arrhythmias. Multivariable logistic regression was used to identify independent risk factors for the primary outcomes. Kaplan-Meier analysis and Cox proportional-hazards model were used to characterize long-term survival. RESULTS: The incidence of POAF was 39%. Median follow-up was 4.9 months (interquartile range, 1.1-42.6 months). Diabetes (odds ratio [OR], 2.2; 95% CI, 1.2-4.1; P = .01) and increasing age (OR, 1.1; 95% CI, 1.0-1.1; P < .001) were risk factors for POAF, whereas New York Heart Association functional class was not. POAF was a risk factor for the development of permanent atrial fibrillation (OR, 3.2; 95% CI 1.9-5.4; P < .001), which was associated with increased risk of neurologic events (OR, 3.8; 95% CI, 1.5-9.7; P = .004). Ultimately, patients with POAF had worse unadjusted (P < .001) and adjusted long-term mortality (hazard ratio, 1.8; 95% CI, 1.1-3.1; P = .03). CONCLUSIONS: POAF is associated with an increased rate of neurologic events, portends development of permanent atrial fibrillation, and is associated with worse long-term survival. POAF is not benign and carries a long-term mortality implication.

NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and its prevalence increases with age. The irregular and rapid contraction of the atria can lead to ineffective blood pumping, local blood stasis, blood clots, ischemic stroke, and heart failure. NADPH oxidases (NOX) and mitochondria are the main sources of reactive oxygen species in the heart, and dysregulated activation of NOX and mitochondrial dysfunction are associated with AF pathogenesis. NOX- and mitochondria-derived oxidative stress contribute to the onset of paroxysmal AF by inducing electrophysiological changes in atrial myocytes and structural remodeling in the atria. Because high atrial activity causes cardiac myocytes to expend extremely high energy to maintain excitation-contraction coupling during persistent AF, mitochondria, the primary energy source, undergo metabolic stress, affecting their morphology, Ca2+ handling, and ATP generation. In this review, we discuss the role of oxidative stress in activating AF-triggered activities, regulating intracellular Ca2+ handling, and functional and anatomical reentry mechanisms, all of which are associated with AF initiation, perpetuation, and progression. Changes in the extracellular matrix, inflammation, ion channel expression and function, myofibril structure, and mitochondrial function occur during the early transitional stages of AF, opening a window of opportunity to target NOX and mitochondria-derived oxidative stress using isoform-specific NOX inhibitors and mitochondrial ROS scavengers, as well as drugs that improve mitochondrial dynamics and metabolism to treat persistent AF and its transition to permanent AF.

The clinical utility of direct His-bundle pacing in patients with heart failure and permanent atrial fibrillation.

In patients with significantly impaired left ventricle function permanent atrial fibrillation (AF) often coexists with symptoms of heart failure. Based on various studies, it is assumed that in patients with heart failure in functional class III and IV AF occurs in 40-50% of patients. AF adversely affects cardiac hemodynamics, and its harmfulness increases particularly in the failing heart. The lack of mechanical function of the left atrium, the usually fast ventricular rate and the irregular sequence of ventricular contraction constitute the spectrum of harmful effects of this arrhythmia. Therefore, the only way to address the underlying problem of AF, which is irregular ventricular rhythm, is to pace the ventricles and to slow or block the AV conduction. Classic, right ventricular pacing is contraindicated in this population as it promotes the abovementioned disorders by initiating additional dyssynchrony of left ventricular contraction with reduction of its contractility and aggravation of AF-related mitral regurgitation. The possibility of direct His bundle pacing (DHBP) significantly extended the clinical armamentarium of cardiac pacing. The restoration of the physiological electrical activation could significantly contribute to echocardiographic and clinical improvement. With time and the development of dedicated tools for direct His bundle pacing the success rate of implantations became more than 90% and the acceptable pacing thresholds under 2.0 V (1 ms) could be achieved in most patients. This contributed to the broader clinical application of DHBP in different patient' groups with various pacing indications. The authors of the paper discuss different electrocardiographic and clinical indications for DHBP.

Atrial fibrillation in dilated cardiomyopathy: Outcome prediction from an observational registry.

BACKGROUND: Little is known about the role of different types of atrial fibrillation (AF) in dilated cardiomyopathy (DCM). We investigated the epidemiological and prognostic impact of different types of AF in DCM during long-term follow-up. METHOD: We evaluated consecutive DCM patients enrolled in the Trieste Muscle Heart Disease Registry. Uni- and multivariable, extended Kaplan-Meier and propensity score-matching analyses were performed for a composite outcome including death/heart transplantation/ventricular-assist device implantation. RESULTS: Out of 1181 DCM patients (71% males, age 49 ± 15 years, left ventricular ejection fraction 33 ± 11%), 46 (3.9%) had baseline permanent AF (permAF), while 66 (5.6%) had a history of paroxysmal/persistent AF. Compared with sinus rhythm (SR) patients, permAF patients were older (48 ± 15 vs. 61 ± 11 respectively, p = 0.001), were more frequently in NYHA class III-IV (18% vs. 30%, p = 0.002) and had larger left atrium diameter (40 ± 8 vs. 50 ± 10 mm, respectively). Paroxysmal/persistent AF patients had intermediate characteristics between permAF and SR. During a median follow-up of 135 (75-210) months, 63 patients developed permAF (0.45 new cases/100patients/year). At multivariable analysis, permAF as a time-dependent variable was an independent outcome predictor (HR 2.45; 95% C.I. 2.61-3.63, p < 0.001), together with creatinine, NYHA class, restrictive filling pattern and moderate-severe mitral regurgitation, while paroxysmal/persistent AF was neutral. Propensity score-matching analysis confirmed the higher rate of primary outcome events in patients with baseline or incident permAF versus patients without permAF during a very long-term follow-up (70% vs. 20%, p < 0.001). CONCLUSIONS: PermAF in a large DCM cohort had low prevalence and incidence but had a relevant. prognostic role on hard outcomes.

Type of atrial fibrillation and outcomes in patients without oral anticoagulants.

BACKGROUND: The effect of type of atrial fibrillation (AF) on adverse outcomes in Chinese patients without oral anticoagulants (OAC) was controversial. HYPOTHESIS: The type of AF associated with adverse outcomes in Chinese patients without OAC. METHODS: A total of 1358 AF patients without OAC from a multicenter, prospective, observational study was included for analysis. Univariable and multivariable Cox regression models were utilized. Net reclassification improvement analysis was performed for the assessment of risk prediction models. RESULTS: There were 896(66%) patients enrolled with non-paroxysmal AF (NPAF) and 462(34%) with paroxysmal AF (PAF). The median age was 70.9 ± 12.6 years, and 682 patients (50.2%) were female. During 1 year of follow-up, 215(16.4%) patients died, and 107 (8.1%) patients experienced thromboembolic events. Compared with the PAF group, NPAF group had a notably higher incidence of all-cause mortality (20.2% vs. 9.4%, p < .001), thromboembolism (10.5% vs. 3.8%, p < .001). After multivariable adjustment, NPAF was a strong predictor of thromboembolism (HR 2.594, 95%CI 1.534-4.386; p < .001), all-cause death (HR 1.648, 95%CI 1.153-2.355; p = .006). Net reclassification improvement analysis indicated that the addition of NPAF to the CHA2 DS2 -VASc score allowed an improvement of 0.37 in risk prediction for thromboembolic events (95% CI 0.21-0.53; p < .001). CONCLUSIONS: In Chinese AF patients who were not on OAC, NPAF was an independent predictor of thromboembolism and mortality. The addition of NPAF to the CHA2 DS2 -VASc score allowed an improvement in the accuracy of the prediction of thromboembolic events.

Long noncoding RNAs and novel inflammatory genes determined by RNA sequencing in human lymphocytes are up-regulated in permanent atrial fibrillation.

Atrial fibrillation (AF) is a common arrhythmia in clinical practice. Currently, approximately 33.5 million individuals are affected by AF globally. AF involves multiple complicated mechanisms which have not been fully investigated yet. RNA sequencing (RNAseq) is an outstanding method for investigation of diseases due to its high-throughput information. Here, RNAseq was applied to determine mRNA and long noncoding RNA (lncRNA) expression profiles in human lymphocytes from 6 permanent atrial fibrillation (pmAF) patients and 6 healthy controls. Quantitative real-time PCR (qRT-PCR) was applied to further validate 3 lncRNAs and 4 inflammatory mRNAs. It was discovered that there were numerous differentially-expressed mRNAs and lncRNAs between these two groups. GO analysis indicated that differentially-expressed mRNAs were mainly involved in native immunity, inflammation, signaling transduction and so forth, and they were also enriched in pathways like TNF signaling pathway, NF-kappa B signaling pathway, Toll-like receptor pathway and NOD-like receptor pathway. Moreover, co-expression network demonstrated that dysregulated mRNAs and lncRNAs in pmAF lymphocytes participated in inflammation, autophagy, mitochondrial functions, oxidative stress, etc. Further validation by qRT-PCR demonstrated mRNAs and lncRNAs were significantly higher in lymphocytes from pmAF patients compared with controls. In conclusion, mRNA and lncRNA expression profiles in lymphocytes are significantly different between pmAF and controls, differentially-expressed mRNAs and lncRNAs are involved in pathways closely associated with inflammation, oxidative stress, autophagy, cell apoptosis and collagen synthesis, suggesting lymphocytes might play indispensable roles in the development of pmAF.