Vagus Nerve Stimulation and Atrial Fibrillation: Revealing the Paradox.

BACKGROUND AND OBJECTIVE: The cardiac autonomic nervous system (CANS) plays an important role in the pathophysiology of atrial fibrillation (AF). Cardiovascular disease can cause an imbalance within the CANS, which may contribute to the initiation and maintenance of AF. Increased understanding of neuromodulation of the CANS has resulted in novel emerging therapies to treat cardiac arrhythmias by targeting different circuits of the CANS. Regarding AF, neuromodulation therapies targeting the vagus nerve have yielded promising outcomes. However, targeting the vagus nerve can be both pro-arrhythmogenic and anti-arrhythmogenic. Currently, these opposing effects of vagus nerve stimulation (VNS) have not been clearly described. The aim of this review is therefore to discuss both pro-arrhythmogenic and anti-arrhythmogenic effects of VNS and recent advances in clinical practice and to provide future perspectives for VNS to treat AF. MATERIALS AND METHODS: A comprehensive review of current literature on VNS and its pro-arrhythmogenic and anti-arrhythmogenic effects on atrial tissue was performed. Both experimental and clinical studies are reviewed and discussed separately. RESULTS: VNS exhibits both pro-arrhythmogenic and anti-arrhythmogenic effects. The anatomical site and stimulation settings during VNS play a crucial role in determining its effect on cardiac electrophysiology. Since the last decade, there is accumulating evidence from experimental studies and randomized clinical studies that low-level VNS (LLVNS), below the bradycardia threshold, is an effective treatment for AF. CONCLUSION: LLVNS is a promising novel therapeutic modality to treat AF and further research will further elucidate the underlying anti-arrhythmogenic mechanisms, optimal stimulation settings, and site to apply LLVNS.

From critic to inspirer: four profiles reveal the belief system and commitment to educational mission of medical academics.

BACKGROUND: The educational beliefs of medical academics influence how they act in class and thus influence student learning. One component of these are beliefs academics hold about the qualities of teachers themselves. These teacher qualities range from behaviours and competencies to more personal attributes such as the teacher's identity and mission. However, it is unclear what medical academics believe to be key teacher qualities. Therefore, this study explored the variety of medical academics' beliefs about 'teacher qualities', aiming to identify and characterise profiles of academics with similar beliefs. METHODS: We interviewed 26 expert academics from two medical schools to explore their beliefs about teacher qualities. A concentric onion-model focusing on teacher qualities was used to analyse and categorise the data deductively. Within each theme we developed subthemes inductively. To gain insight into the variety of beliefs we then clustered the participants into teacher profiles according to the themes. To better understand each of the profiles we carried out a quantitative study of the differences between profiles regarding subthemes, contextual and personal factors, and analysed statistical significance using Fisher's exact- and Student's t-tests for categorical and continuous data, respectively. RESULTS: Four profiles of medical academics were identified, corresponding to the most central theme that each participant had reflected on: the 'Inspirer', 'Role-model', 'Practitioner', and 'Critic'. The focus of the profiles varied from external constraining factors within the 'Critic' profile to affective personal qualities within the 'Role-model' and 'Inspirer' profiles. The profiles could be regarded as hierarchically ordered by inclusiveness. Educational institute was the only significant factor related to the profiles. CONCLUSIONS: Besides the relevance of affective teacher qualities, the 'Inspirer' profile demonstrates the importance of developing a clear mission as a teaching academic, centred around student learning and professional development. In our view, academics who inspire their students continue to be inspired themselves. The practical implications are described for faculty development programmes, and for the potential value of using these profiles within medical schools. In the discourse on educational beliefs, the authors argue that more attention should be paid to affective qualities, in particular to explicating the educational mission of academics.

High Dominant Frequencies and Fractionated Potentials Do Not Indicate Focal or Rotational Activation During AF.

BACKGROUND: Dominant frequencies (DFs) or complex fractionated atrial electrograms (CFAEs), indicative of focal sources or rotational activation, are used to identify target sites for atrial fibrillation (AF) ablation in clinical studies, although the relationship among DF, CFAE, and activation patterns remains unclear. OBJECTIVES: This study sought to investigate the relationship between patterns of activation underlying DF and CFAE sites during AF. METHODS: Epicardial high-resolution mapping of the right and left atrium including Bachmann's bundle was performed in 71 participants. We identified the highest dominant frequency (DFmax) and highest degree of CFAE (CFAEmax) with the use of existing clinical criteria and classified patterns of activation as focal or rotational activation and smooth propagation, conduction block (CB), collision and remnant activity, and fibrillation potentials as single, double, or fractionated potentials containing, respectively, 1, 2, or 3 or more negative deflections. Relationships among activation patterns, DFmax, and potential types were investigated. RESULTS: DFmax were primarily located at the left atrioventricular groove and did not harbor focal activation (proportion focal waves: 0% [IQR: 0%-2%]). Compared with non-DFmax sites, DFmax were characterized by more frequent smooth propagation (22% [IQR: 7%-48%] vs 17% [IQR: 11%-24%]; P = 0.001), less frequent conduction block (69% [IQR: 51%-81%] vs 74% [IQR: 69%-78%]; P = 0.006), a higher proportion of single potentials (72% [IQR: 55%-84%] vs 6%1 [IQR: 55%-65%]; P = 0.003), and a lower proportion of fractionated potentials (4% [IQR: 1%-11%] vs 12% [IQR: 9%-15%]; P = 0.004). CFAEmax were mainly found at the pulmonary veins area, and only 1% [IQR: 0%-2%] of all CFAEmax contained focal activation. Compared with non-CFAEmax sites, CFAEmax sites were characterized by less frequent smooth propagation (1% [IQR: 0%-1%] vs 17% [IQR: 12%-24%]; P < 0.001) and more frequent remnant activity (20% [IQR: 12%-29%] vs 8% [IQR: 5%-10%]; P < 0.001), and harbored predominantly fractionated potentials (52% [IQR: 43%-66%] vs 12% [IQR: 9%-14%]; P < 0.001). CONCLUSIONS: Focal or rotational patterns of activation were not consistently detected at DFmax domains and CFAEmax sites. These findings do not support the concept of targeting DFmax or CFAEmax according to existing criteria for AF ablation.

Does conduction heterogeneity determine the supervulnerable period after atrial fibrillation?

Atrial fibrillation (AF) resumes within 90 s in 27% of patients after sinus rhythm (SR) restoration. The aim of this study is to compare conduction heterogeneity during the supervulnerable period immediately after electrical cardioversion (ECV) with long-term SR in patients with AF. Epicardial mapping of both atria was performed during SR and premature atrial extrasystoles in patients in the ECV (N = 17, age: 73 ± 7 years) and control group (N = 17, age: 71 ± 6 years). Inter-electrode conduction times were used to identify areas of conduction delay (CD) (conduction times 7-11 ms) and conduction block (CB) (conduction times ≥ 12 ms). For all atrial regions, prevalences and length of longest CB and continuous CDCB lines, magnitude of conduction disorders, conduction velocity, biatrial activation time, and voltages did not differ between the ECV and control group during both SR and premature atrial extrasystoles (p ≥ 0.05). Hence, our data suggest that there may be no difference in biatrial conduction characteristics between the supervulnerable period after ECV and long-term SR in AF patients. The supervulnerable period after AF termination is not determined by conduction heterogeneity during SR and PACs. It is unknown to what extent intra-atrial conduction is impaired during the supervulnerable period immediately after ECV and whether different right and left atrial regions are equally affected. This high-resolution epicardial mapping study (upper left panel) of both atria shows that during SR the prevalences and length of longest CB and cCDCB lines (upper middle panel), magnitude of conduction disorders, CV and TAT (lower left panel), and voltages did not differ between the ECV and control group. Likewise, these parameters were comparable during PACs between the ECV and control group (lower left panel). †Non-normally distributed. cm/s = centimeters per second; mm = millimeter; ms = millisecond; AF = atrial fibrillation; AT = activation time; BB = Bachmann's bundle; cCDCB = continuous lines of conduction delay and block; CB = conduction block; CD = conduction delay; CT = conduction time; CV = conduction velocity; ECV = electrical cardioversion; LA = left atrium; LAT = local activation times; PAC = premature atrial complexes; PVA = pulmonary vein area; RA = right atrium; SR = sinus rhythm; TAT = total activation time.

Unipolar atrial electrogram morphology is affected by age: evidence from high-resolution epicardial mapping.

BACKGROUND: It is unknown which features of unipolar atrial electrogram (U-AEGM) morphology are affected by ageing and whether age-related changes in U-AEGM morphology are equally distributed throughout the right and left atria. PATIENTS AND METHODS: Epicardial high-resolution mapping was performed in patients undergoing coronary artery bypass grafting surgery during sinus rhythm (SR). Mapping areas include the right atrium (RA), left atrium (LA), pulmonary vein area (PVA) and Bachmann's bundle (BB). Patients were categorized into a young (age < 60) and aged (age ≥ 60) group. U-AEGM were classified as single potentials (SPs, one deflection), short double potentials (SDPs, deflection interval ≤ 15ms), long double potentials (LDPs, deflection interval > 15ms) and fractionated potentials (FPs, ≥3 deflections). RESULTS: A total of 213 patients (age: 67 (59-73) years; young group N = 58, aged group N = 155) were included. Only at BB, the proportion of SPs (p = 0.007) was significantly higher in the young group, while the proportion of SDPs (p = 0.051), LDPs (p = 0.004) and FPs (p = 0.006) was higher in the aged group. After adjusting for potential confounders, older age was associated with a reduction in SPs [regression coefficient (ß): -6.33, 95% confident interval (CI): -10.37 to -2.30] at the expense of an increased proportion of SDPs (ß: 2.49, 95% CI: 0.09 to 4.89), LDPs (ß: 1.94, 95% CI: 0.21 to 3.68) and FPs (ß: 1.90, 95% CI: 0.62 to 3.18). CONCLUSIONS: Age-related remodeling particularly affects BB as indicated by the decreased amount of non-SP at this location in the elderly.Key MessagesAgeing preferentially affects the morphology of unipolar atrial electrograms recorded at Bachmann's bundle.At Bachmann's bundle, the proportion of short double-, long double- and fractionated potentials increase during ageing at the expense of a decrease in the proportion of single potentials, reflecting aggravation of abnormalities in conduction.The increase in abnormal unipolar atrial electrograms at Bachmann's bundle during ageing supports the concept that Bachmann's bundle may play an important role in development of age-related arrhythmias such as atrial fibrillation.

AF Inducibility Is Related to Conduction Abnormalities at Bachmann's Bundle.

We investigated whether patterns of activation at Bachmann's bundle are related to AF inducibility. Epicardial mapping of Bachmann's bundle during sinus rhythm was performed prior to cardiac surgery (192 electrodes, interelectrode distances: 2 mm). Compared to non-inducible patients (N = 20), patients with inducible AF (N = 34) had longer lines of conduction block (18(2-164) mm vs. 6(2-28) mm, p = 0.048), prolonged total activation time (55(28-143) ms vs. 46(24-73) ms, p = 0.012), multiple wavefronts entering Bachmann's bundle more frequently (64% vs. 37%, p = 0.046) and more often areas of simultaneous activation (conduction velocity > 1.7 m/s, 45% vs. 16%, p = 0.038). These observations further support a relation between conduction abnormalities at Bachmann's bundle and AF inducibility. The next step is to examine whether Bachmann's bundle activation patterns can also be used to identify patients who will develop AF after cardiac surgery during both short- and long-term follow-up.

Exploring Refractoriness as an Adjunctive Electrical Biomarker for Staging of Atrial Fibrillation.

Patients diagnosed with the same subtype of atrial fibrillation according to our current classification system may differ in symptom severity, severity of the arrhythmogenic substrate, and response to antiarrhythmic therapy. Hence, there is a need for an electrical biomarker as an indicator of the arrhythmogenic substrate underlying atrial fibrillation enabling patient-tailored therapy. The aim of this review is to investigate whether atrial refractoriness, a well-known electrophysiological parameter that is affected by electrical remodeling, can be used as an electrical biomarker of the arrhythmogenic substrate underlying atrial fibrillation. We discuss methodologies of atrial effective refractory period assessment, identify which changes in refractoriness-related parameters reflect different degrees of electrical remodeling, and explore whether these parameters can be used to predict clinical outcomes.

Conduction Heterogeneity: Impact of Underlying Heart Disease and Atrial Fibrillation.

OBJECTIVES: The goal of this study is to investigate the impact of various underlying heart diseases (UHDs) and prior atrial fibrillation (AF) episodes on conduction heterogeneity. BACKGROUND: It is unknown whether intra-atrial conduction during sinus rhythm differs between various UHD or is influenced by AF episodes. METHODS: Epicardial sinus rhythm mapping of the right atrium, Bachmann's bundle (BB), left atrium and pulmonary vein area was performed in 447 participants (median age: 67 [interquartile range (IQR): 59 to 73] years) with or without AF undergoing cardiac surgery for ischemic heart disease, (ischemic and) valvular heart disease, or congenital heart disease. Conduction times (CTs) were defined as Δ local activation time between 2 adjacent electrodes and used to assess frequency (CTs ≥ 4 ms) and magnitude of conduction disorders (in increments of 10 ms). RESULTS: When comparing the 3 types of UHD, there were no differences in frequencies and magnitude of CTs at all locations (p ≥ 0.017 and p ≥ 0.005, respectively). Prior AF episodes were associated with conduction slowing throughout both atria (14.9% [IQR: 11.8 to 17.0] vs. 12.8% [IQR: 10.9 to 14.6]; p < 0.001). At BB, CTs with magnitudes ≥30 ms were more common in patients with AF (n = 56.2% vs. n = 36.0%; p < 0.004). CONCLUSIONS: UHD has no impact on the frequency and severity of conduction disorders. AF episodes are associated with more conduction disorders throughout both atria and with more severe conduction disorders at BB. The next step will be to determine the relevance of these conduction disorders for AF development and maintenance.