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Long COVID, die lang anhaltende Krankheit und Erschöpfung, die bei einem kleinen Teil der SARS-CoV-2-Infizierten auftritt, stellt eine zunehmende Belastung für die Betroffenen und die Gesellschaft dar. Eine virtuelle Tagung der Physiological Society im Februar 2022 brachte Kliniker und Forscher zusammen, um das aktuelle Verständnis der Mechanismen, Risikofaktoren und Genesung nach Long COVID zu erörtern. In dieser Übersichtsarbeit werden die Themen behandelt, die sich aus dieser Tagung ergeben haben. Die Übersichtsarbeit befasst sich mit der Natur von Long COVID, untersucht den Zusammenhang mit anderen postviralen Erkrankungen wie der myalgischen Enzephalomyelitis/dem chronischen Erschöpfungssyndrom und zeigt auf, wie die Forschung zu Long COVID helfen kann, Patienten mit allen möglichen postviralen Syndromen besser zu unterstützen. Die Forschung zu Long COVID hat besonders rasche Fortschritte bei Bevölkerungsgruppen gemacht, die ihre körperliche Leistungsfähigkeit routinemäßig überwachen, insbesondere beim Militär und bei Leistungssportlern. In der Übersichtsarbeit wird hervorgehoben, inwiefern das hohe Niveau von Diagnose, Intervention und Erfolgskontrolle in diesen aktiven Bevölkerungsgruppen Informationen über Managementstrategien für die Allgemeinbevölkerung liefern kann. Anschließend wird untersucht, wie eine Schlüsselkomponente der Leistungsüberwachung bei diesen aktiven Bevölkerungsgruppen, das kardiopulmonale Training, Long-COVID-bedingte Veränderungen in der Physiologie aufdeckt – einschließlich Veränderungen der peripheren Muskelfunktion, der ventilatorischen Ineffizienz und der autonomen Dysfunktion. Das Wesen und die Auswirkungen der Dysautonomie werden im Zusammenhang mit dem posturalen orthostatischen Tachykardiesyndrom, der Fatigue und den Behandlungsstrategien, die darauf abzielen, der Überaktivierung des Sympathikus durch Stimulation des Vagusnervs entgegenzuwirken, erörtert. Anschließend untersuchen wir die Mechanismen, die den Symptomen von Long COVID zugrunde liegen. Dabei konzentrieren wir uns auf die gestörte Sauerstoffversorgung durch Mikrokoagulation und die Störung des zellulären Energiestoffwechsels, bevor wir Behandlungsstrategien betrachten, die direkt oder indirekt auf diese Mechanismen abzielen. Dazu gehören ein fernbetreutes Atemmuskeltraining und integrierte Versorgungspfade, die Rehabilitation und medikamentöse Interventionen mit der Erforschung des Zugangs zur Long-COVID-Versorgung in verschiedenen Bevölkerungsgruppen kombinieren. Insgesamt zeigt diese Übersichtsarbeit, wie im Rahmen der physiologischen Forschung die bei Long COVID auftretenden Veränderungen aufgedeckt werden und wie verschiedene therapeutische Strategien zur Bekämpfung dieser Erkrankung entwickelt und getestet werden.

Orthostatic intolerance and other autonomic dysfunction syndromes are emerging as distinct symptom clusters in Long Covid. Often accompanying these are common, multi-system constitutional features such as fatigue, malaise and skin rashes which can signify generalized immune dysregulation. At the same time, multiple autoantibodies are identified in both Covid-related autonomic disorders and non-Covid autonomic disorders, implying a possible underlying autoimmune pathology. The lack of specificity of these findings precludes direct interpretations of cause and association, but their prevalence with its supporting evidence is compelling.

Background Ablation of autonomic ectopy-triggering ganglionated plexuses (ET-GP) has been used to treat paroxysmal atrial fibrillation (AF). It is not known if ET-GP localisation is reproducible between different stimulators or whether ET-GP can be mapped and ablated in persistent AF. We tested the reproducibility of the left atrial ET-GP location using different high-frequency high-output stimulators in AF. In addition, we tested the feasibility of identifying ET-GP locations in persistent atrial fibrillation. Methods Nine patients undergoing clinically-indicated paroxysmal AF ablation received pacing-synchronised high-frequency stimulation (HFS), delivered in SR during the left atrial refractory period, to compare ET-GP localisation between a custom-built current-controlled stimulator (Tau20) and a voltage-controlled stimulator (Grass S88, SIU5). Two patients with persistent AF underwent cardioversion, left atrial ET-GP mapping with the Tau20 and ablation (Precision™, Tacticath™ [n = 1] or Carto™, SmartTouch™ [n = 1]). Pulmonary vein isolation (PVI) was not performed. Efficacy of ablation at ET-GP sites alone without PVI was assessed at 1 year. Results The mean output to identify ET-GP was 34 mA (n = 5). Reproducibility of response to synchronised HFS was 100% (Tau20 vs Grass S88; [n = 16] [kappa = 1, SE = 0.00, 95% CI 1 to 1)][Tau20 v Tau20; [n = 13] [kappa = 1, SE = 0, 95% CI 1 to 1]). Two patients with persistent AF had 10 and 7 ET-GP sites identified requiring 6 and 3 min of radiofrequency ablation respectively to abolish ET-GP response. Both patients were free from AF for > 365 days without anti-arrhythmics. Conclusions ET-GP sites are identified at the same location by different stimulators. ET-GP ablation alone was able to prevent AF recurrence in persistent AF, and further studies would be warranted.

BACKGROUND: Accurately determining arrhythmia mechanism from a 12-lead electrocardiogram (ECG) of supraventricular tachycardia can be challenging. We hypothesized a convolutional neural network (CNN) can be trained to classify atrioventricular re-entrant tachycardia (AVRT) vs atrioventricular nodal re-entrant tachycardia (AVNRT) from the 12-lead ECG, when using findings from the invasive electrophysiology (EP) study as the gold standard. METHODS: We trained a CNN on data from 124 patients undergoing EP studies with a final diagnosis of AVRT or AVNRT. A total of 4962 5-second 12-lead ECG segments were used for training. Each case was labeled AVRT or AVNRT based on the findings of the EP study. The model performance was evaluated against a hold-out test set of 31 patients and compared to an existing manual algorithm. RESULTS: The model had an accuracy of 77.4% in distinguishing between AVRT and AVNRT. The area under the receiver operating characteristic curve was 0.80. In comparison, the existing manual algorithm achieved an accuracy of 67.7% on the same test set. Saliency mapping demonstrated the network used the expected sections of the ECGs for diagnoses; these were the QRS complexes that may contain retrograde P waves. CONCLUSION: We describe the first neural network trained to differentiate AVRT from AVNRT. Accurate diagnosis of arrhythmia mechanism from a 12-lead ECG could aid preprocedural counseling, consent, and procedure planning. The current accuracy from our neural network is modest but may be improved with a larger training dataset.

A multivariate risk score model was proposed by Sieira et al in 2017 for sudden death in Brugada syndrome; their validation in 150 patients was highly encouraging, with a C-index of 0.81; however, this score is yet to be validated by an independent group. A total of 192 records of patients with Brugada syndrome were collected from 2 centers in the United Kingdom and retrospectively scored according to a score model by Sieira et al. Data were compiled summatively over follow-up to mimic regular risk re-evaluation as per current guidelines. Sudden cardiac death survivor data were considered perievent to ascertain the utility of the score before cardiac arrest. Scores were compared with actual outcomes. Sensitivity in our cohort was 22.7%, specificity was 57.6%, and C-index was 0.58. In conclusion, up to 75% of cardiac arrest survivors in this cohort would not have been offered a defibrillator if evaluated before their event. This casts doubt on the utility of the score model for primary prevention of sudden death. Inherent issues with modern risk scoring strategies decrease the likelihood of success even in robustly designed tools such as the Sieira score model.

Aims There is rising healthcare utilization related to the increasing incidence and prevalence of atrial fibrillation (AF) worldwide. Simplifying therapy and reducing hospital episodes would be a valuable development. The efficacy of a streamlined AF ablation approach was compared to drug therapy and a conventional catheter ablation technique for symptom control in paroxysmal AF. Methods and results We recruited 321 patients with symptomatic paroxysmal AF to a prospective randomized, multi-centre, open label trial at 13 UK hospitals. Patients were randomized 1:1:1 to cryo-balloon ablation without electrical mapping with patients discharged same day [Ablation Versus Anti-arrhythmic Therapy for Reducing All Hospital Episodes from Recurrent (AVATAR) protocol]; optimization of drug therapy; or cryo-balloon ablation with confirmation of pulmonary vein isolation and overnight hospitalization. The primary endpoint was time to any hospital episode related to treatment for atrial arrhythmia. Secondary endpoints included complications of treatment and quality-of-life measures. The hazard ratio (HR) for a primary endpoint event occurring when comparing AVATAR protocol arm to drug therapy was 0.156 (95% CI, 0.097–0.250; P < 0.0001 by Cox regression). Twenty-three patients (21%) recorded an endpoint event in the AVATAR arm compared to 76 patients (74%) within the drug therapy arm. Comparing AVATAR and conventional ablation arms resulted in a non-significant HR of 1.173 (95% CI, 0.639–2.154; P = 0.61 by Cox regression) with 23 patients (21%) and 19 patients (18%), respectively, recording primary endpoint events (P = 0.61 by log-rank test). Conclusion The AVATAR protocol was superior to drug therapy for avoiding hospital episodes related to AF treatment, but conventional cryoablation was not superior to the AVATAR protocol. This could have wide-ranging implications on how demand for AF symptom control is met. Trial registration Clinical Trials Registration: NCT02459574.

This paper describes the Bárány Society Classification OverSight Committee (COSC) position on Cervical Dizziness, sometimes referred to as Cervical Vertigo. This involved an initial review by a group of experts across a broad range of fields, and then subsequent review by the Bárány Society COSC. Based upon the so far published literature, the Bárány Society COSC takes the view that the evidence supporting a mechanistic link between an illusory sensation of self-motion (i.e. vertigo – spinning or otherwise) and neck pathology and/or symptoms of neck pain - either by affecting the cervical vertebrae, soft tissue structures or cervical nerve roots - is lacking. When a combined head and neck movement triggers an illusory sensation of spinning, there is either an underlying common vestibular condition such as migraine or BPPV or less commonly a central vestibular condition including, when acute in onset, dangerous conditions (e.g. a dissection of the vertebral artery with posterior circulation stroke and, exceedingly rarely, a vertebral artery compression syndrome). The Committee notes, that migraine, including vestibular migraine, is by far, the commonest cause for the combination of neck pain and vestibular symptoms. The committee also notes that since head movement aggravates symptoms in almost any vestibular condition, the common finding of increased neck muscle tension in vestibular patients, may be linked as both cause and effect, to reduced head movements. Additionally, there are theoretical mechanisms, which have not been explored, whereby cervical pain may promote vaso-vagal, cardio-inhibitory reflexes and hence by presyncopal mechanisms, elicit transient disorientation and/or imbalance. The committee accepts that further research is required to answer the question as to whether those rare cases in which neck muscle spasm is associated with a vague sense of spatial disorientation and/or imbalance, is indeed linked to impaired neck proprioception. Future studies should ideally be placebo controlled and double-blinded where possible, with strict inclusion and exclusion criteria that aim for high specificity at the cost of sensitivity. To facilitate further studies in “cervical dizziness/vertigo”, we provide a narrative view of the important confounds investigators should consider when designing controlled mechanistic and therapeutic studies. Hence, currently, the Bárány COSC refrains from proposing any preliminary diagnostic criteria for clinical use outside a research study. This position may change as new research evidence is provided.

Excessive prolongation of PR interval impairs coupling of AV contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His-bundle pacing allows AV-delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV-optimized His pacing is preferable to no-pacing, in double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200ms and either QRS ≤140ms or right BBB.Patients had atrial and His-bundle leads implanted (and an ICD lead if clinically indicated) and were randomized, to 6-months of pacing and 6-months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. 167 patients were randomized: 90% men, 69±10 years, QRS duration 124±26ms, PR interval 249±59ms, LVEF 33±9%. Neither peak VOHis-bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months. This article is protected by copyright. All rights reserved.

Purpose Left atrial (LA) rapid AF activity has been shown to co-localise with areas of successful atrial fibrillation termination by catheter ablation. We describe a technique that identifies rapid and regular activity. Methods Eight-second AF electrograms were recorded from LA regions during ablation for psAF. Local activation was annotated manually on bipolar signals and where these were of poor quality, we inspected unipolar signals. Dominant cycle length (DCL) was calculated from annotation pairs representing a single activation interval, using a probability density function (PDF) with kernel density estimation. Cumulative annotation duration compared to total segment length defined electrogram quality. DCL results were compared to dominant frequency (DF) and averaging. Results In total 507 8 s AF segments were analysed from 7 patients. Spearman’s correlation coefficient was 0.758 between independent annotators (P P P P Conclusion DCL identifies rapid atrial activity that may represent psAF drivers. This study uses DCL as a tool to evaluate the dynamic, patient specific properties of psAF by identifying rapid and regular activity. If automated, this technique could rapidly identify areas for ablation in psAF.

Aims Accurately determining atrial arrhythmia mechanisms from a 12-lead electrocardiogram (ECG) can be challenging. Given the high success rate of cavotricuspid isthmus (CTI) ablation, identification of CTI-dependent typical atrial flutter (AFL) is important for treatment decisions and procedure planning. We sought to train a convolutional neural network (CNN) to classify CTI-dependent AFL vs. non-CTI dependent atrial tachycardia (AT), using data from the invasive electrophysiology (EP) study as the gold standard. Methods and results We trained a CNN on data from 231 patients undergoing EP studies for atrial tachyarrhythmia. A total of 13 500 five-second 12-lead ECG segments were used for training. Each case was labelled CTI-dependent AFL or non-CTI-dependent AT based on the findings of the EP study. The model performance was evaluated against a test set of 57 patients. A survey of electrophysiologists in Europe was undertaken on the same 57 ECGs. The model had an accuracy of 86% (95% CI 0.77–0.95) compared to median expert electrophysiologist accuracy of 79% (range 70–84%). In the two thirds of test set cases (38/57) where both the model and electrophysiologist consensus were in agreement, the prediction accuracy was 100%. Saliency mapping demonstrated atrial activation was the most important segment of the ECG for determining model output. Conclusion We describe the first CNN trained to differentiate CTI-dependent AFL from other AT using the ECG. Our model matched and complemented expert electrophysiologist performance. Automated artificial intelligence-enhanced ECG analysis could help guide treatment decisions and plan ablation procedures for patients with organized atrial arrhythmias.

Objectives The authors reviewed 3-dimensional electroanatomic maps of perimitral flutter to identify scar-related isthmuses and determine their effectiveness as ablation sites. Background Perimitral flutter is usually treated by linear ablation between the left lower pulmonary vein and mitral annulus. Conduction block can be difficult to achieve, and recurrences are common. Methods Patients undergoing atrial tachycardia ablation using CARTO3 (Biosense Webster Inc., Irvine, California) were screened from 4 centers. Patients with confirmed perimitral flutter were reviewed for the presence of scar-related isthmuses by using CARTO3 with the ConfiDense and Ripple Mapping modules. Results Confirmed perimitral flutter was identified in 28 patients (age 65.2 ± 8.1 years), of whom 26 patients had prior atrial fibrillation ablation. Scar-related isthmus ablation was performed in 12 of 28 patients. Perimitral flutter was terminated in all following correct identification of a scar-related isthmus using ripple mapping. The mean scar voltage threshold was 0.11 ± 0.05 mV. The mean width of scar-related isthmuses was 8.9 ± 3.5 mm with a conduction speed of 31.8 ± 5.5 cm/s compared to that of normal left atrium of 71.2 ± 21.5 cm/s (p < 0.0001). Empirical, anatomic ablation was performed in 16 of 28, with termination in 10 of 16 (63%; p = 0.027). Significantly less ablation was required for critical isthmus ablation compared to empirical linear lesions (11.4 ± 5.3 min vs. 26.2 ± 17.1 min; p = 0.0004). All 16 cases of anatomic ablation were reviewed with ripple mapping, and 63% had scar-related isthmus. Conclusions Perimitral flutter is usually easy to diagnose but can be difficult to ablate. Ripple mapping is highly effective at locating the critical isthmus maintaining the tachycardia and avoiding anatomic ablation lines. This approach has a higher termination rate with less radiofrequency ablation required.

Blood pressure regulation is an automatic, moment-by-moment buffering of the blood pressure in response to physiological changes such as orthostasis, exercise and haemorrhage. This finely orchestrated reflex is called the baroreflex. It is a regulated arc of afferent, central and efferent arms. Multiple physiological changes occur with ageing that can disrupt this reflex, making blood pressure regulation less effective. In addition, multiple changes can occur with ageing-related diseases such as neurodegeneration, atherosclerosis, deconditioning and polypharmacy. These changes commonly result in orthostatic hypotension, hypertension or both, and are consistently associated with multiple adverse outcomes. In this article, we discuss the healthy baroreflex, and physiological and pathophysiological reasons for impaired baroreflex function in older people. We discuss why the common clinical manifestations of orthostatic hypotension and concomitant supine hypertension occur, and strategies for balancing these conflicting priorities. Finally, we discuss strategies for treating them, outlining our practice alongside consensus and expert guidance.

Background Ganglionated plexuses (GPs) are implicated in atrial fibrillation (AF). Endocardial high‐frequency stimulation (HFS) delivered within the local atrial refractory period can trigger ectopy and AF from specific GP sites (ET‐GP). The aim of this study was to understand the role of ET‐GP ablation in the treatment of AF. Methods Patients with paroxysmal AF indicated for ablation were recruited. HFS mapping was performed globally around the left atrium to identify ET‐GP. ET‐GP was defined as atrial ectopy or atrial arrhythmia triggered by HFS. All ET‐GP were ablated, and PVs were left electrically connected. Outcomes were compared with a control group receiving pulmonary vein isolation (PVI). Patients were followed‐up for 12 months with multiple 48‐h Holter ECGs. Primary endpoint was ≥30 s AF/atrial tachycardia in ECGs. Results In total, 67 patients were recruited and randomized to ET‐GP ablation (n = 39) or PVI (n = 28). In the ET‐GP ablation group, 103 ± 28 HFS sites were tested per patient, identifying 21 ± 10 (20%) GPs. ET‐GP ablation used 23.3 ± 4.1 kWs total radiofrequency (RF) energy per patient, compared with 55.7 ± 22.7 kWs in PVI (p =

Objectives This multicenter registry aimed to assess the reproducibility and safety of intentional coronary vein exit and carbon dioxide insufflation to facilitate subxiphoid epicardial ac...

The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system may play a role in atrial fibrillation (AF).We hypothesized that ablating the ectopy-triggering GPs (ET-GPs) prevents AF.GANGLIA-AF (ClinicalTrials.gov identifier NCT02487654) was a prospective, randomized, controlled, 3-center trial. ET-GPs were mapped using high frequency stimulation, delivered within the atrial refractory period and ablated until nonfunctional. If triggered AF became incessant, atrioventricular dissociating GPs were ablated. We compared GP ablation (GPA) without pulmonary vein isolation (PVI) against PVI in patients with paroxysmal AF. Follow-up was for 12 months including 3-monthly 48-hour Holter monitors. The primary end point was documented ≥30 seconds of atrial arrhythmia after a 3-month blanking period.A total of 102 randomized patients were analyzed on a per-protocol basis after GPA (n = 52; 51%) or PVI (n = 50; 49%). Patients who underwent GPA had 89 ± 26 high frequency stimulation sites tested, identifying a median of 18.5% (interquartile range 16%-21%) of GPs. The radiofrequency ablation time was 22.9 ± 9.8 minutes in GPA and 38 ± 14.4 minutes in PVI (P.0001). The freedom from ≥30 seconds of atrial arrhythmia at 12-month follow-up was 50% (26 of 52) with GPA vs 64% (32 of 50) with PVI (log-rank, P = .09). ET-GPA without atrioventricular dissociating GPA achieved 58% (22 of 38) freedom from the primary end point. There was a significantly higher reduction in antiarrhythmic drug usage postablation after GPA than after PVI (55.5% vs 36%; P = .05). Patients were referred for redo ablation procedures in 31% (16 of 52) after GPA and 24% (12 of 50) after PVI (P = .53).GPA did not prevent atrial arrhythmias more than PVI. However, less radiofrequency ablation was delivered to achieve a higher reduction in antiarrhythmic drug usage with GPA than with PVI.

Background His bundle pacing (HBP) can be achieved in 2 ways: selective HBP (S-HBP), where the His bundle is captured alone, and nonselective HBP (NS-HBP), where local myocardium is also captured, resulting a pre-excited electrocardiogram appearance. Objective We assessed the impact of this ventricular pre-excitation on left and right ventricular dyssynchrony. Methods We recruited patients who displayed both S-HBP and NS-HBP. We performed noninvasive epicardial electrical mapping for left and right ventricular activation time (LVAT and RVAT) and pattern. Results Twenty patients were recruited. In the primary analysis, the mean within-patient change in LVAT from S-HBP to NS-HBP was -5.5 ms (95% confidence interval: -0.6 to -10.4, noninferiority P < .0001). NS-HBP did not prolong RVAT (4.3 ms, -4.0 to 12.8, P = .296) but did prolong QRS duration (QRSd, 22.1 ms, 11.8 to 32.4, P = .0003). In patients with narrow intrinsic QRS (n = 6), NS-HBP preserved LVAT (-2.9 ms, -9.7 to 4.0, P = .331) but prolonged QRS duration (31.4 ms, 22.0 to 40.7, P = .0003) and mean RVAT (16.8 ms, -5.3 to 38.9, P = .108) compared to S-HBP. Activation pattern of the left ventricular surface was unchanged between S-HBP and NS-HBP, but NS-HBP produced early basal right ventricular activation that was not seen in S-HBP. Conclusion Compared to S-HBP, local myocardial capture during NS-HBP produces pre-excitation of the basal right ventricle resulting in QRS duration prolongation. However, NS-HBP preserves the left ventricular activation time and pattern of S-HBP. Left ventricular dyssynchrony is not an important factor when choosing between S-HBP and NS-HBP in most patients., Graphical abstract

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background; Left bundle area pacing is a novel technique that provides direct stimulation of cardiac conduction tissue in order to deliver physiological ventricular activation. The approach for left bundle area pacing is transseptal lead implantation, where the lead is advanced from the right ventricular side of the septum to the left ventricular side to capture the proximal left bundle. Observational data suggests that whilst this is a safe and feasible method, implant success rate is not 100%, and appears to be lower in patients with a cardiac resynchronization therapy (CRT) indication rather than a bradycardia indication for pacing. The mechanisms for failure to advance the lead through the ventricular septum are not well understood. Purpose; We used pre-procedural CMR to determine whether there are features which can help identify patients where lead implantation may be challenging. We assessed whether the extent and location of septal late gadolinium enhancement identified patients in whom left bundle area pacing will be challenging. We hypothesized that the presence of extensive scar in the septum impedes advancing the lead to the left ventricular septum and prevents capture of the left bundle. Methods; Patients underwent cardiac MRI including motion corrected free-breathing late gadolinium enhancement imaging1 before implantation. Scar was quantified using the full height half maximum method and expressed as the overall proportion of myocardial mass in the basal anteroseptal and basal inferoseptal segments, as shown in Figure 1. Left bundle area pacing was then attempted in patients with a CRT indication for pacing. We compared the extent of septal scar between patients in whom left bundle area pacing was achieved and those where there was failure to advance the lead deep into the septum. Results; 12 patients (11 male, 1 female), with average age 72 (IQR 63 to 78) and LVEF 30% (IQR 26 to 33) were studied. There was failure to advance the lead deep into the septum in 4 patients. There was a significantly higher basal septal scar burden in those patients where there was failure to advance the left bundle lead compared to those in which left bundle capture was achieved as shown in Figure 2 (median 55% and 5% respectively, p-value 0.02 by Wilcoxon signed rank test). Conclusion; The presence and extent of late gadolinium enhancement in the basal septum appears to be an important determinant of successful implantation of left bundle pacing lead using current implant technology. This may be because extensive septal scar prevents advancement of the pacing lead through the septum. Cardiac MRI before left bundle area pacing is likely to be useful in procedural planning.

Background: Atrial fibrillation (AF) and ventricular fibrillation (VF) are complex heart rhythm disorders and may be sustained by distinct electrophysiological mechanisms. Disorganised self-perpetuating multiple-wavelets and organised rotational drivers (RDs) localising to specific areas are both possible mechanisms by which fibrillation is sustained. Determining the underlying mechanisms of fibrillation may be helpful in tailoring treatment strategies. We investigated whether global fibrillation organisation, a surrogate for fibrillation mechanism, can be determined from electrocardiograms (ECGs) using band-power (BP) feature analysis and machine learning.Methods: In this study, we proposed a novel ECG classification framework to differentiate fibrillation organisation levels. BP features were derived from surface ECGs and fed to a linear discriminant analysis classifier to predict fibrillation organisation level. Two datasets, single-channel ECGs of rat VF (n = 9) and 12-lead ECGs of human AF (n = 17), were used for model evaluation in a leave-one-out (LOO) manner.Results: The proposed method correctly predicted the organisation level from rat VF ECG with the sensitivity of 75%, specificity of 80%, and accuracy of 78%, and from clinical AF ECG with the sensitivity of 80%, specificity of 92%, and accuracy of 88%.Conclusion: Our proposed method can distinguish between AF/VF of different global organisation levels non-invasively from the ECG alone. This may aid in patient selection and guiding mechanism-directed tailored treatment strategies.

Background: The mechanisms underlying atrial fibrillation (AF) remain controversial. We developed Representation of Electrical Tracking or Origin-Mapping to characterize activation wavefronts by direction and uniformity, accumulating data as an orbital plot and analyzed as frequency histograms. We applied this technique to patients undergoing AF ablation to determine if AF activation is random. Methods: Patients undergoing persistent AF ablation were recruited, and an AFocusII was positioned at multiple left atrial locations and kept steady for 1 minute to collect electrograms. The AFocusII was returned to the original site and position after >10 minutes for a repeat 1-minute data collection. Data were exported to custom Representation of Electrical Tracking or Origin-Mapping software, and 30 seconds consecutive time windows at each location were studied using frequency histograms of wavefronts. R50 (the range in degrees containing 50% of the total activation) was used as a method to enable statistical comparisons of activation patterns. Electrogram characterization into categories of complex fractionated atrial electrograms by Ensite Precision was subjected to similar analysis. Results: Consecutive 30 seconds segments were studied at 161 locations in 18 pts. Mean overlap between frequency histograms was 79.5%±7.7 (95% CI, 78.3–80.7). Nine patients underwent delayed mapping at the same location, and mean overlap between the first 30 seconds and >10 minute interval was 73%±11.8 and 71.9%±13.6 for consecutive 30-second segments. Stability was confirmed using R50 (Bland-Altman mean difference: 0.87°; limits of agreement: −34.0 to 36.0; r =0.005; P =0.95). A greater variance in R50 was observed between different locations within a patient than the variance within the same locations (intraclass correlation=0.765; P P r =0.36, P Conclusions: There appears to be preferential activation patterns during persistent AF indicating spatiotemporal stability. This has important implication to our mechanistic understanding of persistent AF.

Orthostatic hypotension (OH) is very common in older people and is encountered daily in emergency departments and medical admissions units. It is associated with a higher risk of falls, fractures, dementia and death, so prompt recognition and treatment are essential. In this review article, we describe the physiology of standing (orthostasis) and the pathophysiology of orthostatic hypotension. We focus particularly on aspects pertinent to older people. We review the evidence and consensus management guidelines for all aspects of management. We also tackle the challenge of concomitant orthostatic hypotension and supine hypertension, providing a treatment overview as well as practical suggestions for management. In summary, orthostatic hypotension (and associated supine hypertension) are common, dangerous and disabling, but adherence to simple structures management strategies can result in major improvements.

Head-up tilt test (TT) has been used for >50 years to study heart rate/blood pressure adaptation to positional changes, to model responses to haemorrhage, to assess orthostatic hypotension, and to evaluate haemodynamic and neuroendocrine responses in congestive heart failure, autonomic dysfunction, and hypertension. During these studies, some subjects experienced syncope due to vasovagal reflex. As a result, tilt testing was incorporated into clinical assessment of syncope when the origin was unknown. Subsequently, clinical experience supports the diagnostic value of TT. This is highlighted in evidence-based professional practice guidelines, which provide advice for TT methodology and interpretation, while concurrently identifying its limitations. Thus, TT remains a valuable clinical asset, one that has added importantly to the appreciation of pathophysiology of syncope/collapse and, thereby, has improved care of syncopal patients., Graphical Abstract

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): British Heart Foundation Background Cardiac resynchronization therapy delivered via biventricular pacing is thought to improve haemodynamic function through resynchronization of ventricular activation. Biventricular pacing also improves ventricular filling by shortening atrioventricular delay. Quantifying the relative contributions of these two mechanisms requires atrioventricular delay to be altered while left bundle branch block is preserved. This occurs when the His bundle is paced at an output below the left bundle branch block correction threshold. Purpose We performed His bundle pacing with preservation of left bundle branch block to measure the relative contributions of atrioventricular delay shortening and ventricular resynchronisation to the overall haemodynamic benefit of biventricular pacing. Methods Patients with left bundle branch block referred for conventional cardiac resynchronization therapy with biventricular pacing were recruited. Using a high precision, beat-by-beat systolic blood pressure assessment protocol, we assessed the haemodynamic effects of biventricular pacing and temporary His bundle pacing with left bundle branch block preservation at a full range of atrioventricular delays. We used non-invasive epicardial mapping (ECGI) to assess left ventricular activation time. Left bundle branch block preservation was defined as Results In 19 patients, His bundle pacing with preservation of left bundle branch block produced a peak systolic blood pressure improvement of 5.1mmHg (95% confidence interval: 2.2 to 8.0, p = 0.0013) compared to AAI pacing. In 16 of these patients, biventricular pacing was performed and produced a peak systolic blood pressure improvement of 7.1mmHg (3.8 to 10.4, p Conclusion Biventricular pacing in left bundle branch block improves haemodynamic function through ventricular resynchronization and shortening of atrioventricular delay. The majority of benefit appears to be produced by atrioventricular delay shortening. When left bundle branch block is not corrected, His bundle pacing may still produce considerable haemodynamic improvement through this mechanism. Abstract Figure.

Background Conduction channels have been demonstrated within the postinfarct scar and seem to be co-located with the isthmus of ventricular tachycardia (VT). Mapping the local scar potentials (SPs) that define the conduction channels is often hindered by large far-field electrograms generated by healthy myocardium. Objective The purpose of this study was to map conduction channel using ripple mapping to categorize SPs temporally and anatomically. We tested the hypothesis that ablation of early SPs would eliminate the latest SPs without direct ablation. Methods Ripple maps of postinfarct scar were collected using the PentaRay (Biosense Webster) during normal rhythm. Maps were reviewed in reverse, and clusters of SPs were color-coded on the geometry, by timing, into early, intermediate, late, and terminal. Ablation was delivered sequentially from clusters of early SPs, checking for loss of terminal SPs as the endpoint. Results The protocol was performed in 11 patients. Mean mapping time was 65 ± 23 minutes, and a mean 3050 ± 1839 points was collected. SP timing ranged from 98.1 ± 60.5 ms to 214.8 ± 89.8 ms post QRS peak. Earliest SPs were present at the border, occupying 16.4% of scar, whereas latest SPs occupied 4.8% at the opposing border or core. Analysis took 15 ± 10 minutes to locate channels and identify ablation targets. It was possible to eliminate latest SPs in all patients without direct ablation (mean ablation time 16.3 ± 11.1 minutes). No VT recurrence was recorded (mean follow-up 10.1 ± 7.4 months). Conclusion Conduction channels can be located using ripple mapping to analyze SPs. Ablation at channel entrances can eliminate the latest SPs and is associated with good medium-term results.

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): NIHR Imperial Biomedical Research Centre Introduction Implantable Cardioverter-Defibrillators (ICDs) cannot distinguish between ventricular tachycardia (VT) with haemodynamic compromise from haemodynamically tolerated VT to ensure that therapies are delivered only when necessary. Currently, unnecessary therapies are reduced by longer duration thresholds and higher rate thresholds. This can result in ICDs withholding or delaying therapies during haemodynamically compromising VT while potentially still providing therapies during rapid or prolonged VT that is haemodynamically well tolerated. Laser doppler perfusion monitoring (LDPM) allows assessment of peripheral blood flow as a surrogate for haemodynamic status. We have previously demonstrated that laser doppler perfusion signals, analysed using an electro-mechanical coupling algorithm (SafeShock), can reliably identify loss of perfusion during ventricular fibrillation (VF), as well as discriminate VF from simulated lead fractures and T wave over-sensing. The utility of LDPM signals in VT, however, has not been established. Purpose In this study we assessed the utility of LDPM using the SafeShock algorithm to discriminate haemodynamically tolerated VT from VT with haemodynamic compromise. Methods Recruited participants underwent a rapid ventricular pacing protocol to simulate VT at different rates. Pacing was performed using the right ventricular lead of an implanted pacing device or a temporary pacing wire in the right ventricular apex. 3-lead ECG, blood pressure (either invasively using a radial artery catheter or non-invasively using beat-by-beat finometry) and LDPM signal were continuously recorded during the protocol. LDPM signals during simulated VT were analysed using the SafeShock electro-mechanical algorithm and compared to blood pressure change from baseline intrinsic rhythm to simulated VT. Results We obtained 588 recordings of simulated VT in 56 patients at rates of 100 bpm, 120 bpm, 140 bpm, 160 bpm, 180 bpm and 200 bpm. Percentage change in systolic blood pressure from baseline to VT correlated with LDPM-derived perfusion value during VT (Spearman’s Rho = 0.7786, p < 0.0001). Using a cut-off of 5 units, perfusion value predicted a 20% drop in systolic blood pressure in VT with an accuracy of 89.4% (sensitivity 94.8%, specificity 83.6%, p value Conclusions Peripheral perfusion measurements, analysed using an electro-mechanical algorithm, can accurately discriminate haemodynamically tolerated VT from VT with haemodynamic compromise. ICDs with integrated LDPM sensors and algorithms could make therapy decisions based on the circulatory status of patients with arrhythmias not just rate and duration parameters. This could reduce unnecessary therapies while facilitating prompt treatment of compromising arrhythmias. Abstract Figure 1

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): BRAVO trial: BHF SP/10/002/28189, FS/10/038, FS/11/92/29122, FS/13/44/30291) National Institute for Health Research Imperial Biomedical Research Centre. HOPE-HF trial: British Heart Foundation (CS/15/3/31405, FS/13/44/30291, FS/15/53/31615, FS/14/27/30752, FS/10/038). Introduction The optimal atrioventricular (AV) delay for implantable cardiac devices can be derived by echocardiography or beat-by-beat blood pressure measurements. However, both of these approaches are labour intensive and neither could be incorporated into an implantable cardiac device for frequent repeated optimisations. Laser Doppler perfusion monitoring (LDPM) measures blood flow through tissue. LDPM has been miniaturised ready to be incorporated into future implantable cardiac devices. Purpose We studied if LDPM is a clinically reliable alternative method to blood-pressure measurements to determine optimal AV delay. Methods Data from 58 patients undergoing 94 clinical AVD optimisations using LDPM and simultaneous non-invasive beat-by-beat blood pressure was obtained. The optimal AV delay for each method and for each optimisation was determined using a curve of haemodynamic response to switching from AAI (reference state) to DDD (test state) at a series of AV delays (40, 80, 120, 160, 200, 240 ms). We then compared the derived optimal AV delays between the two measurement approaches. We also assessed the impact of the paced heart-rate on agreement between laser Doppler and Blood-Pressure derived optimal AV delays. Results The AV delay derived using LDPM was not clinically significant different from that derived by blood pressure changes. The median difference was -9ms (IQR -26 to 7, p = 0.05). Variability between the two methods was low (median absolute deviation 17ms). Optimisations performed at higher heart-rates resulted in a non-significant smaller difference between the LDPM and blood-pressure derived AV delays (median absolute deviation 12 vs 22 ms, p = 0.11). Conclusions Optimal AVDs derived from non-invasive blood-pressure or laser Doppler perfusion methods are clinically equivalent. The addition of laser Doppler to future implantable cardiac devices may enable devices to dynamically and reliably optimise AV delays. Abstract Figure 1

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): British Heart Foundation Background: His bundle pacing can be achieved in two ways selective His bundle pacing, where the His bundle is captured alone, and non-selective His bundle pacing, where local myocardium is also captured resulting a pre-excited ECG appearance. We assessed the impact of this ventricular pre-excitation on left and right ventricular dys-synchrony. Methods We recruited patients who displayed both selective and non-selective His bundle pacing. We performed non-invasive epicardial electrical mapping to determine left and right ventricular activation times and patterns. Results In the primary analysis (n = 20, all patients), non-selective His bundle pacing did not prolong LVAT compared to select His bundle pacing by a pre-specified non-inferiority margin of 10ms (LVAT prolongation: -5.5ms, 95% confidence interval (CI): -0.6 to -10.4, non-inferiority p In patients with narrow intrinsic QRS (n = 6), non-selective His bundle pacing preserved left ventricular activation time (-2.9ms, 95%CI: -9.7 to 4.0, p = 0.331) but prolonged QRS duration (31.4ms, 95%CI: 22.0 to 40.7, p = 0.0003) and mean right ventricular activation time (16.8ms, 95%CI: -5.3 to 38.9, p = 0.108) compared to selective His bundle pacing. Activation pattern of the left ventricular surface was unchanged between selective and non-selective His bundle pacing. Non-selective His bundle pacing produced early basal right ventricular activation, which was not observed with selective His bundle pacing. Conclusions Compared to selective His bundle pacing, local myocardial capture during non-selective His bundle pacing produces right ventricular pre-excitation resulting in prolongation of QRS duration. However, non-selective His bundle pacing preserves the left ventricular activation time and pattern of selective His bundle pacing. When choosing between selective and non-selective His bundle pacing, left ventricular dyssynchrony is not an important factor. Abstract Figure: Selective vs Non-Selective HBP

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): British Heart Foundation Imperial Centre of Research Excellence Background/Introduction ECG algorithms for identifying accessory pathway (AP) locations are inaccurate and difficult to use. Human expert interpretation is poorly reproducible. Artificial intelligence (AI) techniques such as machine learning can improve accuracy in classification tasks by eschewing theory-driven predictions. More reproducible and accurate AP localisation could shorten procedure time and personalise ablation consent. Purpose We developed a neural network to perform AP localisation using 12-lead ECGs. Its decision-making process was analysed to enable explainability of the neural network. Methods A convolutional neural network was trained on raw, digital, intra-procedural 12-lead ECGs of patients with manifest APs who underwent successful ablation. ECGs were labelled with AP locations as left-sided, septal or right-sided using procedure reports, fluoroscopy and electro-anatomical maps. Accuracy of the neural network was assessed via 4-fold cross-validation and was compared to the Arruda algorithm. Five cardiologists were also assessed for their accuracy in determining locations in sub-groups of cases. The neural network was retrospectively analysed to identify areas of ECGs most influential to its predictions using importance mapping. Results In 156 cases, accuracy of the neural network (92.9%) was significantly higher than the Arruda algorithm (76.9%; p The figure shows (A) architecture of the neural network, (B) accuracy of the neural network, Arruda algorithm and five cardiologists, (*, p = 0.05 – 0.01; **, p = 0.01 – 0.001; ***, p = 0.001 - 0.0001; ****, p Conclusion AI ECG interpretation allows accurate, reproducible prediction of AP locations, superior to conventional algorithms and human interpretation. Although AI decision-making is thought of as a ‘black box’, explanation visualisation techniques such as importance mapping allow humans to understand aspects of how a neural network make decisions. A prospectively validated neural network could be integrated into clinical practice to improve pre-procedural AP localisation. Abstract Figure. Summary of results