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Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Introduction Cardiac resynchronisation therapy (CRT) in the form of His bundle CRT and left bundle area CRT can be more effective than the gold standard, biventricular pacing (BVP). In BVP scar burden is known to predict response whether this is true for these novel modalities is not known. Purpose The purpose of this study was to determine whether left ventricular scar burden assessed using cardiac MRI can be used to predict the electrical and acute haemodynamic response to two novel CRT modalities. Methods Patients with standard CRT indications were recruited. They underwent a pre-procedure cardiac MRI, with late gadolinium enhancement (LGE) to quantify scar. His bundle CRT (His CRT) and left bundle area CRT (LBA CRT) were attempted. The electrical response was measured using high precision non-invasive mapping ECGi (CardioInsight, Medtronic). The haemodynamic response was measured with a high precision protocol. We investigated the impact of scar and baseline electrical characteristic on ECGi and haemodynamic response. Results 26 patients were recruited (85% male, mean age 69 ± 10, with ischaemic cardiomyopathy in 35%). LGE was observed in 96% of cases and the mean (range 1-39%). We found a significant correlation between scar extent and the electrical response with both modalities. There was a significant correlation between a lower scar burden and better electrical response. For His CRT the reduction in left ventricular activation time was better with lower scar burden (R= 0.77, p < 0.01, Picture 1), for LBA CRT for reduction in left ventricular activation was also better with lower scar burden (R = 0.53, p = 0.05, Picture 2). With His CRT there was also a significant correlation between lower scar extent and better acute haemodynamic response ( R = 0.6, p = 0.002) but this was not observed with LBA CRT (R = 0.07, p = 0.77). Conclusion Left ventricular myocardial scar can be used to predict the electrical response to two different conduction system CRT modalities.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation. Background HOPE-HF was a randomised, placebo-controlled, cross-over trial of AV-optimised His bundle pacing in patients with heart failure (LVEF ≤40%), a PR interval (≥200ms) and without left bundle branch block.1,2. In this analysis we studied the impact of baseline PR interval and acute blood pressure change at the optimal AV-delay on the placebo-controlled effect of His bundle pacing on the trial endpoints of peak VO2 (primary) and patient symptoms (using the Minnesota Living with Heart Failure Questionnaire). Methods and Results 167 patients were successfully implanted and randomised to 6 month blocks of pacing and placebo. We performed a non-invasive, high-precision protocol to calculate the optimal AV delay and associated acute blood-pressure response at randomisation. To test the impact of the baseline PR interval and acute BP response on the placebo-controlled effect of AV-optimised His bundle pacing on endpoints we compared Bayesian ordinal regression models and the relative explained variance (REV) of variables in the model. There was weak evidence that His-bundle pacing improved peak VO2 across all patients (OR 1.31, 95% CrI 0.86 to 2.01, Pr(OR > 1)=89%). The baseline PR interval had little impact on this benefit (REV 0%), and the blood pressure response was more likely (88% vs 12%) to be predictive. However, there was strong evidence that overall AV-optimised His-bundle pacing improved patient symptoms as compared to placebo (OR 1.58, 95% CrI 1.04 to 2.40, Pr(OR>1)=98%). Again, the baseline PR interval had little impact on this benefit (REV 0%) and the blood pressure response was much more likely (97% vs 3%) to be predictive. Higher acute BP increments led to greater placebo-controlled improvements in MLWHF at 6-months. Conclusion An individual’s acute BP response with AV-optimised His-pacing is a powerful predictor of their placebo-controlled improvement in symptoms (MLWHF) at 6-months. This can form the basis of patient selection for future studies and clinical practice.

Background Fragmentation of the QRS complex, as a surrogate for scar or functionally disrupted ventricular activation, has been postulated as a risk factor for malignant ventricular arrhythmias across a range of cardiac diagnoses including cardiomyopathies, channelopathies and myocardial infarction. Fragmentation is subtle on the conventionally filtered 12-lead ECG and can easily be missed or over-diagnosed. Isolation of high-frequency (HF) QRS components could overcome this to demonstrate easily identifiable fragmentation but this has previously been limited by technological constraints resulting in a limited range of measured frequencies (150–300Hz). Ultra-high-frequency ECG (UHF-ECG) is a novel technology that utilises amplification and signal-averaging techniques to reliably measure frequencies up to 1000Hz. Purpose We explored the use of UHF-ECG in arrhythmia risk stratification. Methods We recruited 60 participants to undergo UHF-ECG recordings, including 23 healthy volunteers and 37 patients with inherited arrhythmia syndromes: 25 hypertrophic cardiomyopathy (HCM), 5 Brugada syndrome, 4 arrhythmogenic cardiomyopathy, 3 idiopathic ventricular fibrillation, 2 long QT syndrome and 1 non-ischaemic dilated cardiomyopathy. The arrhythmia risk status of patients with inherited disease was classified, by two independent researchers, into high or low risk based on their history of cardiac arrest, sustained ventricular arrhythmia, appropriate therapy, syncope and programmed ventricular stimulation result. A third researcher adjudicated disagreement. Two further researchers, blinded to aforementioned risk status, independently assessed the UHF-ECG recordings of all participants. Results 40 patients were classified as low risk, and 20 as high. Healthy volunteer UHF-ECGs showed uniform ventricular activation with single HF peaks in each lead. High-risk patients' UHF-ECGs showed multiple HF peaks, representing QRS fragmentation. The maximum number of HF peaks in any lead was used to measure severity of fragmentation. Example UHF-ECGs are shown in Figure 1. Fragmentation severity (number of peaks) correlated with arrhythmia risk status (chi-square statistic = 8.95, p-value = 0.03) across all participants (Figure 2) and when comparing high to low risk patients with inherited disease. UHF-ECG fragmentation could be observed even when the 12-lead ECG did not show any observable fragmentation. Among patients with inherited disease, patients with HCM showed the largest difference in UHF-ECG fragmentation between high and low risk. UHF-ECG fragmentation analysis showed excellent reproducibility with no difference in number of peaks identified between two independent assessors. Conclusion We demonstrate proof-of-concept that a novel ultra-high-frequency tool for measuring a broad range of high frequency QRS components can be used for sudden death risk stratification in patients with inherited cardiac conditions. Funding Acknowledgement Type of funding sources: None.

Introduction Chronic RV pacing has been recognised as being harmful to cardiac function. Patients undergoing a de novo pacemaker implant with even mild LV impairment are recommended to instead receive a physiological pacing strategy (biventricular or conduction system pacing [CSP]). No corresponding guideline recommendation exists for patients who already have a pacemaker. Methods We undertook a random-effects meta-analysis of all RCTs and observational studies covering device upgrade to biventricular pacing or conduction system pacing. Results 6 RCTs assessing effect of upgrade to BiV pacing randomising 161 patients were eligible for analysis. Eligible observational studies included 46 of BiV upgrade and 7 of CSP upgrade totalling 2795 patients. Mean LVEF improved by +8.3% from 34.4% in BiV upgrade RCTs (p=0.001) and +8.3% from 25.7% in BiV upgrade observational studies (p In observational studies of upgrade to CSP, LVEF increased by +10.1% from 38.4% (p=0.001) despite less severe LV impairment at baseline (p=0.004 vs mean EF in BiV RCTs and p LVESV decreased significantly by −25.4 ml, −23.7 ml, and −19.8 ml in BiV RCTs, BiV observational studies and CSP observational studies. Significant changes were also seen in NYHA class (decreased by −0.4, −0.8 and −1.0 respectively). Minnesota Heart Failure Score (−6.9 points) and peak oxygen uptake (+1.1 ml/kg/min) increased significantly in RCTs of BiV upgrade. This was also seen in observational studies of BiV upgrade (−21.0 points and +2.63 ml/kg/min respectively). Conclusions RCTs and observational studies of upgrade to BiV pacing show significant physiological and symptomatic benefit. Observational studies of CSP upgrade show similar benefit with significant improvements in LVEF, LVESV and NYHA class in patients with an even milder degree of baseline LV impairment. Funding Acknowledgement Type of funding sources: None.