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Patients who had discontinued statins because of side effects received four bottles of a statin, four bottles of placebo, and four empty bottles, each to be used for 1 month in a random sequence for 12 months. The symptom burden with placebo was 90% of the symptom burden with the statin.

Background: The prognostic impact of ventricular tachycardia (VT) catheter ablation is an important outstanding research question. We undertook a reconstructed individual patient data meta-analysis of randomised controlled trials comparing ablation to medical therapy in patients developing VT after MI. Methods: We systematically identified all trials comparing catheter ablation to medical therapy in patients with VT and prior MI. The prespecified primary endpoint was reconstructed individual patient assessment of all-cause mortality. Prespecified secondary endpoints included trial-level assessment of all-cause mortality, VT recurrence or defibrillator shocks and all-cause hospitalisations. Prespecified subgroup analysis was performed for ablation approaches involving only substrate modification without VT activation mapping. Sensitivity analyses were performed depending on the proportion of patients with prior MI included. Results: Eight trials, recruiting a total of 874 patients, were included. Of these 874 patients, 430 were randomised to catheter ablation and 444 were randomised to medical therapy. Catheter ablation reduced all-cause mortality compared with medical therapy when synthesising individual patient data (HR 0.63; 95% CI [0.41–0.96]; p=0.03), but not in trial-level analysis (RR 0.91; 95% CI [0.67–1.23]; p=0.53; I2=0%). Catheter ablation significantly reduced VT recurrence, defibrillator shocks and hospitalisations compared with medical therapy. Sensitivity analyses were consistent with the primary analyses. Conclusion: In patients with postinfarct VT, catheter ablation reduces mortality.

Introduction: Reducing unnecessary and inappropriate implantable cardioverter defibrillator (ICD) therapies reduces mortality. This was demonstrated in studies that investigated using higher rates for treatment zones and longer detection windows. ICDs currently do not utilise haemodynamic measurements to guide therapies. We have previously shown that a potentially implantable sensor can reliably identify loss of perfusion in ventricular fibrillation. It is possible that programming even longer detection windows could further reduce unnecessary shocks; however, it is not known in how many patients this may be beneficial, and the risk with adopting this approach is that appropriate shocks would be withheld for longer than necessary in the presence of reduced coronary blood flow (CBF). A disadvantage of using higher heart rate zones is that slower haemodynamically compromising VTs are left untreated. We investigated the impact of simulated VT on CBF and invasive blood pressure (BP). The aims were to determine whether detection windows could potentially be safely extended in some patients during VT and to identify what proportion of patients poorly tolerate episodes of slower VT. Methods: We recruited patients undergoing a clinically indicated invasive coronary angiogram. We simulated VT by delivering right ventricular VVI pacing, via a temporary wire. Each patient underwent a randomized ventricular pacing (Vp) protocol (140, 160, 180 and 200 bpm) for a minimum of 30 seconds. During each Vp protocol, continuous 3-lead ECG, invasive beat-by-beat arterial BP and invasive CBF, using a combowire in the mid-left anterior descending artery, were recorded. Significant haemodynamic compromise was defined as a reduction in CBF and/or a sustained drop of 30% in systolic BP (SBP) compared with measurements made during baseline rhythm. Results: A total of 21 patients were recruited, of whom 8 (38%) were female. The mean age was 65 years, and 5 patients (24%) had a left ventricular ejection fraction less than 35%. Data were collected during 145 simulated VT episodes (25 at 200 bpm, 42 at 180 bpm, 39 at 160 and 140 bpm, and 38 at 120 bpm). Results showed that 28% of simulated VT episodes at a rate of 200 bpm were haemodynamically tolerated. This suggests that ICD therapies could potentially be delayed for longer during these VT episodes to allow more time for VT to self-terminate. Haemodynamic compromise was observed in a proportion of slower simulated VT episodes (rates that are below current guidelines for primary prevention programming). For the combined endpoint of decline in CBF and SBP, VT was not tolerated in 11 (28.9%) at 120 bpm, 12 (30.8%) at 140 bpm, 22 (56.4%) at 160 bpm and 28 (66.7%) at 180 bpm. An isolated reduction in CBF had a greater impact on haemodynamic compromise at slower rates (9 (23.7%) at 120 bpm vs 1 (2.6%) at 160 bpm), whereas faster rates were driven by sustained drops in SBP. Proportionally, more patients had haemodynamic compromise at higher heart rates compared with slower heart rates (p=0.016). Conclusion: One-third of simulated VT episodes at 200 bpm were haemodynamically well tolerated. This suggests VT detection windows could potentially be safely extended, with the aim of reducing unnecessary therapies in a significant number of VT episodes. In contrast, many episodes of slower VT were poorly tolerated, implying that therapies may be beneficial. Thus, ICD programming could be further optimized with haemodynamically guided therapies compared with currently used methods, which exclusively rely on the electrogram. [Image Omitted]

Introduction: Conduction system pacing is a novel way for delivering cardiac resynchronisation therapy (CRT). This may deliver more effective ventricular resynchronisation than the gold standard, biventricular pacing (BVP). In BVP scar burden is known to impact response but whether this is true for conduction system pacing is unknown. Methods: Patients with standard CRT indications were recruited. They underwent a pre-procedure cardiac MRI, with late gadolinium enhancement to assess scar. Scar burden was quantified as the percentage of the amount of myocardium for each segment and the whole of the left ventricle (total scar). Conduction system pacing with both His bundle CRT (HB-CRT) and left bundle area CRT (LBA-CRT) was attempted in everyone, and the modality that delivered the narrowest QRS duration was selected. The electrical response was measured using non-invasive mapping (ECGi, CardioInsight, Medtronic). The haemodynamic response was measured with a high precision protocol. We investigated the impact of scar on the electrical and haemodynamic response. Results: A total of 26 patients were recruited, 85% male, mean age 69 ± 10 years, ischaemic cardiomyopathy in 35% and mean QRS duration 160 ± 15. LGE was observed in 96% of cases, mean total scar burden was 13 ± 12% (range 1–39%). We found a significant correlation between amount of scar and both the electrical and acute haemodynamic response (Figure 1). Patients with a lower scar burden obtained a greater improvement in both electrical resynchronisation (R=0.55, 95% CI 0.21–0.77, p<0.01, for reduction in left ventricular activation time [LVAT]), and acute haemodynamic response (R=0.5, 95% CI 0.18–0.76, p=0.005 for increase in acute systolic blood pressure). Conclusion: Conduction system pacing appears to be less effective in patients with a high left ventricular scar burden. We observed a strong correlation between scar burden and both ventricular electrical resynchronisation and acute haemodynamic response. This information may help patient selection for conduction system CRT. Alternative CRT modalities or combinations of modalities warrant further investigation in this challenging group of patients. ❑ [Image Omitted]

Introduction: Conduction system pacing in the form of His bundle pacing (HBP) can deliver more effective ventricular resynchronization compared to biventricular pacing, which translates to greater acute haemodynamic benefit. Left bundle branch pacing (LBBP) has potential advantages over HBP; capture thresholds are typically lower and it can correct left bundle branch block occurring as a result of more distal conduction system disease. A potential disadvantage of LBBP compared to His-CRT is that is does not typically capture the right bundle branch and therefore results in delayed right ventricular activation. It is not known whether this delayed activation produces important reductions in the improvements of cardiac function compared to HBP. We conducted a within-patient comparison of acute electrical and haemodynamic response to HBP, LBBP and biventricular pacing (BVP) in patients with a CRT indication. Methods: Patients with severely impaired left ventricular systolic function and QRS duration >120 ms were recruited into the study. HBP and LBBP was delivered to all patients and BVP was also delivered to a subgroup of these patients. Conduction system capture was confirmed using standard criteria. We defined successful delivery of resynchronization as a reduction of at least 15 ms in left ventricular activation time. We assessed the acute electrical response by measuring the change in QRS duration (12-lead ECG) and ventricular activation times (ECGi, Medtronic). Acute haemodynamic response was assessed using a high precision haemodynamic protocol. Results: 15 patients were recruited (12 male, 3 female), mean age 66.5 years (IQR 55–76), LVEF 32% (IQR 30–35) and QRS duration 172 ms (IQR 166–178). HBP and LBBP both achieved better ventricular resynchronization compared with biventricular pacing. Reduction in left ventricular activation times were significantly greater with both HBP and LBBP compared to BVP (22 ms; 95% CI, 9.8–34.2; p<0.01 for HBP, and 26.7 ms; 95% CI, 16.0–37.5; p<0.01 for LBP). The reduction in left ventricular activation times with HBP was 46 ms ± 8.6 (95% CI, 37.5–54.5). LBBP also resulted in a reduction in left ventricular activation time of 45 ± 8.5 (95% CI, 36.5–53.3). There was no significant difference between the two modalities (-2.1; 95% CI, -11.4–7.1; p=0.6). All three modalities improved acute systolic blood pressure (median increase; HBP 11.3 mmHg, LBBP 9.1 mmHg and BVP 6.7 mmHg) (Figure 1). When we compared HBP and LBBP there was a trend towards greater improvement with HBP compared to LBBP, but this did not reach statistical significance (1.05; 95% CI, -6.1–4.0; p=0.66). Conclusion: Conduction system pacing with HBP and LBBP both have the potential to deliver more effective ventricular resynchronization compared to biventricular pacing. The delayed right ventricular activation with LBBP does not appear to significantly impact acute cardiac function. LBBP is therefore a very promising method for delivering cardiac resynchronization therapy. [Image Omitted]

Background: It is assumed that resynchronisation of the ventricles in patients with heart failure and left bundle branch block (LBBB) delivers the most benefit in biventricular pacing (BVP). Because cardiac resynchronisation therapy (CRT) with BVP both shortens atrioventricular delay and reduces ventricular dyssynchrony, it is difficult to isolate their individual impact. Objectives: In this invasive study, using His bundle pacing to shorten atrioventricular delay without correcting LBBB, we aimed to isolate the contributions of atrioventricular delay shortening versus ventricular resynchronisation. Methods: Nineteen patients with LBBB referred for cardiac resynchronisation therapy were recruited. To assess the atrioventricular delay, only patients in sinus rhythm on the day of the procedure were included in the study. Using high precision, beat-by-beat assessment of acute systolic blood pressure, we performed a within-patient comparison of the haemodynamic effects of (i) BVP (which both shortens atrioventricular delay and reduces QRS duration), (ii) His bundle pacing with preservation of LBBB (which only shortens atrioventricular delay), and (iii) right ventricular apical pacing. Results: BVP improved systolic blood pressure (+7.1 mmHg vs intrinsic conduction, 95% CI +3.6 to +10.7; p<0.001, n=16) (Figure 1). Atrioventricular delay optimization without correction of LBBB also improved systolic blood pressure (+5.1 mmHg, 95%CI +2.0 to +8.2; p=0.0026, n=19), which was two-thirds of the effect size of BVP. In contrast, right ventricular apical pacing did not (+1.2 mmHg, 95%CI -0.8 to +3.1; p=0.206, n=10). Conclusion: This study demonstrated that the main mechanism of haemodynamic benefit in BVP appears to be shortening of atrioventricular delay, rather than resynchronisation of ventricles. This will allow exploration of additional pacing modalities other than conventional BVP, in delivering the most clinical benefit of CRT, even if they do not correct LBBB. ❑ [Image Omitted]

Introduction: Left bundle branch block (LBBB) is associated with an increased risk of ventricular arrhythmia. Biventricular pacing (BVP) improves symptoms, systolic left ventricular function and mortality in heart failure with LBBB, but can be pro-arrhythmic. His bundle pacing (HBP) can overcome LBBB to produce more synchronous ventricular activation than BVP, but it is not known how ventricular repolarisation heterogeneity is affected, which is important in arrhythmogenesis. We set to out to measure the dispersion of repolarisation and activation recovery-interval (ARI, a surrogate for action potential duration) in narrow QRS, LBBB, BVP and HBP. Methods: Patients were recruited into two groups. In the first group, patients with heart failure and LBBB scheduled to undergo clinically indicated BVP implant procedures were recruited. They underwent temporary HBP to attempt reverse LBBB during the BVP procedure. If HBP shortened activation time by ≥10 ms, patients were included (HBP cardiac resynchronisation therapy [CRT]). In the second group patients with normal, narrow QRS were recruited. Non-invasive electrocardiographic imaging was used to measure the following parameters in narrow QRS, LBBB, BVP and HBP: left ventricular activation time, left ventricular repolarisation time dispersion and left ventricular ARI dispersion. Results: A total of 21 patients in whom HBP shortened LV activation time by >10 ms and an equal number of individuals with narrow intrinsic QRS were recruited. LV repolarisation dispersion was reduced by HBP-CRT (-42.0 ms, 95% confidence interval (CI) -52.3 to -31.7; p<0.001) but not by BVP (+11.9 ms, -6.24 to 30.1; p=0.182). The mean within-patient change in LV repolarisation dispersion from BVP to HBP-CRT was -56.5 ms (-70.5 to 42.5; p<0.001). LV repolarisation dispersion with HBP-CRT was not different from individuals with narrow intrinsic QRS (difference: 2.75 ms, -16.2 to 21.7; p=0.981). The magnitude of reduction in LV repolarisation dispersion with HBP-CRT from intrinsic LBBB appeared to be similar to the magnitude of LV activation time shortening (-45.9 ms, -59.3 to -32.4). However, LV activation recovery interval dispersion was also reduced by HBP-CRT (-56.5 ms, -70.5 to -42.5 ms; p<0.001). Repolarisation mapping demonstrated normalisation of repolarisation pattern by HBP-CRT. Conclusions: HBP-CRT can normalise repolarisation dispersion, producing more physiological repolarisation compared with BVP, which does not resolve the repolarisation abnormality of LBBB. HBP-CRT improves repolarisation through both activation resynchronisation and modulation of action-potential duration. If these acute results translate to longer-term outcomes, HBP-CRT may reduce the risk of ventricular arrhythmias in heart failure with LBBB to a greater extent than BVP. ❑

Background: Accurately determining atrial arrhythmia mechanisms from a 12-lead ECG can be challenging. Given the high success rate of cavotricuspid isthmus (CTI) ablation, accurate identification of CTI-dependent typical atrial flutter (AFL) is important for treatment decisions and procedure planning. Machine learning, with convolutional neural networks (CNNs) in particular, has been used to classify arrhythmias using the 12-lead ECG with great accuracy. However, most studies use human interpretation of the ECG as the ground truth to label the arrhythmia ECGs. Therefore, these neural networks can only ever be as good as expert human interpretation. We hypothesised that a CNN can be trained to classify CTI-dependent AFL vs non-CTI-dependent atrial tachycardia (AT), when using findings from the invasive electrophysiology (EP) study as the gold standard. Methods: We trained a CNN on data from 231 patients undergoing EP studies for atrial tachyarrhythmia. A total of 13,500 5-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 and cardiologists in Europe was undertaken on the same 57 ECGs. Results: The model had an accuracy of 86% (95% CI 0.77–0.95). The F1 score was 0.87. The AT/AFL network correctly identified AT 82% and AFL 90% of the time. A saliency map can be used to help understand why a CNN predicted a particular outcome. This is achieved by mapping the outcome back to key areas of the input that most influenced the network in producing the classification result. Figure 1 presents the saliency mappings of an example 12-lead ECG for each class of AFL and AT. The network used the expected sections of the ECGs for diagnoses; these were the P-wave segments and not the QRS or other unexpected segments. There were 12 respondents in the clinician survey. These respondents included nine electrophysiologists. The median accuracy was 78% (range 70–86%). The electrophysiologists had a median accuracy of 79% (range 70–84%). Humans were more likely to incorrectly diagnose AFL as AT (on average incorrect diagnoses: 9 AFL, 1 AT). In comparison, the neural network most often incorrectly diagnosed AT as AFL (incorrect diagnoses: 5 AT, 3 AFL). 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%. Conclusion: We describe the first neural network trained to differentiate CTI-dependent AFL from other atrial tachycardias. Our model at least matched and complemented expert electrophysiologist performance. Automated artificial intelligence-enhanced ECG analysis could help guide treatment decisions and plan ablation procedures for patients with organised atrial arrhythmias. ❑ Figure 1 [Image Omitted]

Introduction: Biventricular pacing (BVP) improves morbidity and mortality in patients with heart failure and Left Bundle Branch Block (LBBB), but there is considerable scope for improved outcomes if more effective resynchronisation could be achieved. His bundle pacing (HBP) appears to be able to overcome LBBB and is a new method for Cardiac Resynchronisation Therapy (CRT). We performed an acute crossover comparison of HBP and BVP measuring effects on left ventricular activation time and pattern and acute haemodynamic function. Methods: Twenty-four patients with LBBB referred for a BVP device implantation based on standard clinical criteria were recruited. Using high precision, beat-by-beat assessment of acute systolic blood pressure, we compared haemodynamic responses to BVP and temporary HBP. We used ECGI to measure left ventricular activation time (LVAT) and to perform epicardial propagation mapping (EPM) allowing visualisation of activation patterns. Eleven patients with normal, narrow QRS undergoing ECGI recordings were analysed for comparison. Results: In 17 patients, temporary HBP reduced activation time (termed ‘His-CRT’) and the full haemodynamic and ventricular activation dataset was successfully acquired. His-CRT was more effective in delivering ventricular resynchronisation than BVP; it delivered significantly greater reductions in QRS duration (–18.6 ms, 95% CI –31.6 to –5.7, p=0.007) and LVAT (–26 ms 95% CI –41 to –21, p=0.002). This translated into a significantly greater acute systolic blood pressure response (4.6 mmHg, 95% CI 0.2 to 9.1, p=0.04). Changes in activation time showed a close correlation with changes in acute systolic blood pressure (R=0.7, p=0.04). EPM revealed two distinct activation patterns in LBBB. In the majority of patients (20/24, 83.3%), regions of epicardial propagation block were observed. In the remainder of patients with LBBB (4/24, 16.7%), a second pattern was observed: slow propagation across the LV epicardium without any appearance of blocked or regionally slowed conduction. In patients where His-CRT produced LVAT-95 values within the normal range defined by participants with normal, narrow QRS (24–70 ms), lines of block disappeared with HBP which produces smooth, rapid activation of the LV indistinguishable from activation pattern in patients with normal QRS (Figure 1). In patients without lines of block, LVAT was not reduced by HBP. Regression modelling demonstrated that propagation block predicted LVAT-95 shortening (p=0.04). Conclusions: EPM derived from ECGI allows accurate non-invasive discrimination of LBBB with regions of propagation block, that is potentially amenable to resynchronisation by HBP, from diffuse slow conduction that cannot be corrected. When HBP normalises left ventricular activation time, the activation pattern produced is physiological and indistinguishable from normal activation with intact conduction system. This translates to improved haemodynamic function compared to BVP. [Image Omitted]

Introduction: Left bundle area pacing is a novel conduction system technique that is rapidly expanding. When the left bundle branch (LBB) alone is captured the 12-lead ECG shows an R prime in lead V1 indicative of delayed right ventricular activation. This is usually seen in unipolar pacing. Right septal myocardial capture can be achieved by anodal stimulation. This overcomes the delay in right ventricular activation. Whether overcoming this delay in right ventricular activation has positive effects on cardiac function is unknown and has never been investigated. We sought to address whether overcoming delayed right ventricular activation is associated with any haemodynamic benefit. Methods: Patients were recruited from our pacing clinic and before attempting left bundle branch pacing (LBBP). We reviewed the 12-lead electrocardiograms of all patients to distinguish LBB-only capture from LBB plus right septal myocardial capture. With LBB-only capture there is an R prime in lead V1, this is eliminated when right septal capture is achieved by anodal stimulation. We selected patients who demonstrated both types of capture. High precision haemodynamic protocol was used to measure systolic blood pressure change with each capture type compared to a reference baseline. We undertook a within-patient comparison of QRS duration, pacing threshold and systolic blood pressure between the two types of capture. Results: 15 patients with permanent LBBP demonstrated both LBB-only capture and LBB plus anodal capture and were included in the study. The average age was 68 ± 11 years and 11 (73%) were male. Bradycardia was the pacing indication in 3 (20%) patients, heart failure in 11 (73%) and pre-TAVI in 1 (7%). LBB plus right septal capture was associated with significantly narrower QRS duration compared to LBB-only capture (-11.7 ms; 95% CI, -15.7 to -7.6 ms; p<0.0001). However, LBB plus right septal capture required higher pacing outputs, typically seen in bipolar pacing configuration. The mean threshold with LBB-only capture was 0.69 V ± 0.25 at 0.4 ms, and LBB plus right septal capture was 3.28 V ± 2.16 at 0.4 ms; the difference was statistically significant (2.6V; 95% CI, 1.4–3.8 V; p=0.0004). Despite the narrower QRS, there was no significant difference observed in systolic blood pressure between the two capture types (-0.96 mmHg; 95% CI, -3.3–1.4 mmHg; p>0.05) (Figure 1). Conclusion: Left bundle pacing achieves left bundle branch capture at a low output, but this is associated with delayed right ventricular activation. Anodal stimulation can be used to achieve right septal capture, and lead to earlier activation of the right ventricle. However, this requires significantly higher outputs and does not offer any haemodynamic advantage. This has important implications for device programming.