Therapeutic options for neurocardiogenic syncope: a meta-analysis of randomised trials with and without blinding.

BACKGROUND: Neurocardiogenic syncope is a common condition with significant associated psychological and physical morbidity. The effectiveness of therapeutic options for neurocardiogenic syncope beyond placebo remains uncertain. METHODS: The primary endpoint was the risk ratio (RR) of spontaneously recurring syncope following any therapeutic intervention. We also examined the effect of blinding on treatment efficacy. We identified all randomised trials which evaluated the effect of any pharmacological, device-based or supportive intervention on patients with a history of syncope. A systematic search was conducted on Medline, Embase, PubMed databases and Cochrane Central Register for Controlled Trials from 1950 to 25 April 2023. Event rates, their RRs and 95% CIs were calculated, and a random-effects meta-analysis was conducted for each intervention. Data analysis was performed in R using RStudio. RESULTS: We identified 47 eligible trials randomising 3518 patients. Blinded trials assessing syncope recurrence were neutral for beta blockers, fludrocortisone and conventional dual-chamber pacing but were favourable for selective serotonin reuptake inhibitors (SSRIs) (RR 0.40, 95% CI 0.26 to 0.63, p<0.001), midodrine (RR 0.70, 95% CI 0.53 to 0.94, p=0.016) and closed-loop stimulation (CLS) pacing (RR 0.15, 95% CI 0.07 to 0.35, p<0.001). Unblinded trials reported significant benefits for all therapy categories other than beta blockers and consistently showed larger benefits than blinded trials. CONCLUSIONS: Under blinded conditions, SSRIs, midodrine and CLS pacing significantly reduced syncope recurrence. Future trials for syncope should be blinded to avoid overestimating treatment effects. PROSPERO REGISTRATION NUMBER: CRD42022330148.

Catheter Ablation for Ventricular Tachycardia After MI: A Reconstructed Individual Patient Data Meta-analysis of Randomised Controlled Trials.

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.

Guided implantation of a leadless left ventricular endocardial electrode and acoustic transmitter using computed tomography anatomy, dynamic perfusion and mechanics, and predicted activation pattern.

BACKGROUND: The WiSE-CRT System (EBR systems, Sunnyvale, CA) permits leadless left ventricular pacing. Currently, no intraprocedural guidance is used to target optimal electrode placement while simultaneously guiding acoustic transmitter placement in close proximity to the electrode to ensure adequate power delivery. OBJECTIVE: The purpose of this study was to assess the use of computed tomography (CT) anatomy, dynamic perfusion and mechanics, and predicted activation pattern to identify both the optimal electrode and transmitter locations. METHODS: A novel CT protocol was developed using preprocedural imaging and simulation to identify target segments (TSs) for electrode implantation, with late electrical and mechanical activation, with ≥5 mm wall thickness without perfusion defects. Modeling of the acoustic intensity from different transmitter implantation sites to the TSs was used to identify the optimal transmitter location. During implantation, TSs were overlaid on fluoroscopy to guide optimal electrode location that were evaluated by acute hemodynamic response (AHR) by measuring the maximal rate of left ventricular pressure rise with biventricular pacing. RESULTS: Ten patients underwent the implantation procedure. The transmitter could be implanted within the recommended site on the basis of preprocedural analysis in all patients. CT identified a mean of 4.8 ± 3.5 segments per patient with wall thickness < 5 mm. During electrode implantation, biventricular pacing within TSs resulted in a significant improvement in AHR vs non-TSs (25.5% ± 8.8% vs 12.9% ± 8.6%; P < .001). Pacing in CT-identified scar resulted in either failure to capture or minimal AHR improvement. The electrode was targeted to the TSs in all patients and was implanted in the TSs in 80%. CONCLUSION: Preprocedural imaging and modeling data with intraprocedural guidance can successfully guide WiSE-CRT electrode and transmitter implantation to allow optimal AHR and adequate power delivery.

Uncertainty aware training to improve deep learning model calibration for classification of cardiac MR images.

Quantifying uncertainty of predictions has been identified as one way to develop more trustworthy artificial intelligence (AI) models beyond conventional reporting of performance metrics. When considering their role in a clinical decision support setting, AI classification models should ideally avoid confident wrong predictions and maximise the confidence of correct predictions. Models that do this are said to be well calibrated with regard to confidence. However, relatively little attention has been paid to how to improve calibration when training these models, i.e. to make the training strategy uncertainty-aware. In this work we: (i) evaluate three novel uncertainty-aware training strategies with regard to a range of accuracy and calibration performance measures, comparing against two state-of-the-art approaches, (ii) quantify the data (aleatoric) and model (epistemic) uncertainty of all models and (iii) evaluate the impact of using a model calibration measure for model selection in uncertainty-aware training, in contrast to the normal accuracy-based measures. We perform our analysis using two different clinical applications: cardiac resynchronisation therapy (CRT) response prediction and coronary artery disease (CAD) diagnosis from cardiac magnetic resonance (CMR) images. The best-performing model in terms of both classification accuracy and the most common calibration measure, expected calibration error (ECE) was the Confidence Weight method, a novel approach that weights the loss of samples to explicitly penalise confident incorrect predictions. The method reduced the ECE by 17% for CRT response prediction and by 22% for CAD diagnosis when compared to a baseline classifier in which no uncertainty-aware strategy was included. In both applications, as well as reducing the ECE there was a slight increase in accuracy from 69% to 70% and 70% to 72% for CRT response prediction and CAD diagnosis respectively. However, our analysis showed a lack of consistency in terms of optimal models when using different calibration measures. This indicates the need for careful consideration of performance metrics when training and selecting models for complex high risk applications in healthcare.

Feasibility of mapping and ablating ectopy-triggering ganglionated plexus reproducibly in persistent atrial fibrillation.

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.

Upgrading right ventricular pacemakers to biventricular pacing or conduction system pacing: a systematic review and meta-analysis.

Guidelines recommend patients undergoing a first pacemaker implant who have even mild left ventricular (LV) impairment should receive biventricular or conduction system pacing (CSP). There is no corresponding recommendation for patients who already have a pacemaker. We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies assessing device upgrades. The primary outcome was the echocardiographic change in LV ejection fraction (LVEF). Six RCTs (randomizing 161 patients) and 47 observational studies (2644 patients) assessing the efficacy of upgrade to biventricular pacing were eligible for analysis. Eight observational studies recruiting 217 patients of CSP upgrade were also eligible. Fourteen additional studies contributed data on complications (25 412 patients). Randomized controlled trials of biventricular pacing upgrade showed LVEF improvement of +8.4% from 35.5% and observational studies: +8.4% from 25.7%. Observational studies of left bundle branch area pacing upgrade showed +11.1% improvement from 39.0% and observational studies of His bundle pacing upgrade showed +12.7% improvement from 36.0%. New York Heart Association class decreased by -0.4, -0.8, -1.0, and -1.2, respectively. Randomized controlled trials of biventricular upgrade found improvement in Minnesota Heart Failure Score (-6.9 points) and peak oxygen uptake (+1.1 mL/kg/min). This was also seen in observational studies of biventricular upgrades (-19.67 points and +2.63 mL/kg/min, respectively). In studies of the biventricular upgrade, complication rates averaged 2% for pneumothorax, 1.4% for tamponade, and 3.7% for infection over 24 months of mean follow-up. Lead-related complications occurred in 3.3% of biventricular upgrades and 1.8% of CSP upgrades. Randomized controlled trials show significant physiological and symptomatic benefits of upgrading pacemakers to biventricular pacing. Observational studies show similar effects between biventricular pacing upgrade and CSP upgrade.

Convergent ablation for persistent atrial fibrillation: outcomes from a single-centre real-world experience.

OBJECTIVES: Atrial fibrillation (AF) is common and can cause significant morbidity and detriment to quality of life. Success rates for conventional catheter ablation are suboptimal in persistent AF (PsAF), especially when longstanding. Convergent hybrid ablation combines endoscopic surgical epicardial and endocardial catheter ablation. It offers promise in treating PsAF. We aimed to evaluate outcomes at our centre following convergent ablation. METHODS: We conducted an observational study of patients undergoing ablation from 2012 to 2019 at a London cardiac centre. Sixty-seven patients underwent convergent ablation entailing epicardial ablation, mostly via sub-xiphoid access, followed by endocardial left atrial catheter ablation. Baseline and follow-up data were obtained retrospectively from clinical records. Primary outcome was freedom from AF on/off anti-arrhythmic drugs after 12-month follow-up. Secondary outcomes included freedom from AF over the entire follow-up, freedom from anti-arrhythmic drugs, freedom from atrial arrhythmias, symptom status, repeat ablation and complications. RESULTS: At baseline, 80.6% had PsAF >1 year (80.6%), 49.3% had body mass index >30 kg/m2 at baseline and 19.4% had left ventricular ejection fraction of 40% or less. The median follow-up was 2.3 (1.4-3.7) years. Freedom from AF recurrence was 81.3% at 1 year and 61.5% over overall follow-up. Eleven patients (16.4%) required redo AF ablation. Prolonged AF duration was associated with increased recurrence at 12 months and duration >5 years with a shorter time to recurrence on Kaplan-Meier analysis, but this and other factors did not significantly impact the AF recurrence during the overall follow-up period. CONCLUSIONS: Convergent ablation had good 1-year and overall success rates for treating PsAF. Our results in a diverse, real-world population support the potential of convergent ablation in patients with challenging to treat PsAF.

A multimodal deep learning model for cardiac resynchronisation therapy response prediction.

We present a novel multimodal deep learning framework for cardiac resynchronisation therapy (CRT) response prediction from 2D echocardiography and cardiac magnetic resonance (CMR) data. The proposed method first uses the 'nnU-Net' segmentation model to extract segmentations of the heart over the full cardiac cycle from the two modalities. Next, a multimodal deep learning classifier is used for CRT response prediction, which combines the latent spaces of the segmentation models of the two modalities. At test time, this framework can be used with 2D echocardiography data only, whilst taking advantage of the implicit relationship between CMR and echocardiography features learnt from the model. We evaluate our pipeline on a cohort of 50 CRT patients for whom paired echocardiography/CMR data were available, and results show that the proposed multimodal classifier results in a statistically significant improvement in accuracy compared to the baseline approach that uses only 2D echocardiography data. The combination of multimodal data enables CRT response to be predicted with 77.38% accuracy (83.33% sensitivity and 71.43% specificity), which is comparable with the current state-of-the-art in machine learning-based CRT response prediction. Our work represents the first multimodal deep learning approach for CRT response prediction.

Standard care vs. TRIVEntricular pacing in Heart Failure (STRIVE HF): a prospective multicentre randomized controlled trial of triventricular pacing vs. conventional biventricular pacing in patients with heart failure and intermediate QRS left bundle branch block.

AIMS: To determine whether triventricular (TriV) pacing is feasible and improves CRT response compared to conventional biventricular (BiV) pacing in patients with left bundle branch block (LBBB) and intermediate QRS prolongation (120-150 ms). METHODS AND RESULTS: Between October 2015 and November 2019, 99 patients were recruited from 11 UK centres. Ninety-five patients were randomized 1:1 to receive TriV or BiV pacing systems. The primary endpoint was feasibility of TriV pacing. Secondary endpoints assessed symptomatic and remodelling response to CRT. Baseline characteristics were balanced between groups. In the TriV group, 43/46 (93.5%) patients underwent successful implantation vs. 47/49 (95.9%) in the BiV group. Feasibility of maintaining CRT at 6 months was similar in the TriV vs. BiV group (90.0% vs. 97.7%, P = 0.191). All-cause mortality was similar between TriV vs. BiV groups (4.3% vs. 8.2%, P = 0.678). There were no significant differences in echocardiographic LV volumes or clinical composite scores from baseline to 6-month follow-up between groups. CONCLUSION: Implantation of two LV leads to deliver and maintain TriV pacing at 6 months is feasible without significant complications in the majority of patients. There was no evidence that TriV pacing improves CRT response or provides additional clinical benefit to patients with LBBB and intermediate QRS prolongation and cannot be recommended in this patient group. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT02529410.

Time-Averaged Wavefront Analysis Demonstrates Preferential Pathways of Atrial Fibrillation, Predicting Pulmonary Vein Isolation Acute Response.

Electrical activation during atrial fibrillation (AF) appears chaotic and disorganised, which impedes characterisation of the underlying substrate and treatment planning. While globally chaotic, there may be local preferential activation pathways that represent potential ablation targets. This study aimed to identify preferential activation pathways during AF and predict the acute ablation response when these are targeted by pulmonary vein isolation (PVI). In patients with persistent AF (n = 14), simultaneous biatrial contact mapping with basket catheters was performed pre-ablation and following each ablation strategy (PVI, roof, and mitral lines). Unipolar wavefront activation directions were averaged over 10 s to identify preferential activation pathways. Clinical cases were classified as responders or non-responders to PVI during the procedure. Clinical data were augmented with a virtual cohort of 100 models. In AF pre-ablation, pathways originated from the pulmonary vein (PV) antra in PVI responders (7/7) but not in PVI non-responders (6/6). We proposed a novel index that measured activation waves from the PV antra into the atrial body. This index was significantly higher in PVI responders than non-responders (clinical: 16.3 vs. 3.7%, p = 0.04; simulated: 21.1 vs. 14.1%, p = 0.02). Overall, this novel technique and proof of concept study demonstrated that preferential activation pathways exist during AF. Targeting patient-specific activation pathways that flowed from the PV antra to the left atrial body using PVI resulted in AF termination during the procedure. These PV activation flow pathways may correspond to the presence of drivers in the PV regions.

The physiological effects of cardiac resynchronization therapy on aortic and pulmonary flow and dynamic and static components of systemic impedance.

BACKGROUND: Patients who improve following cardiac resynchronization therapy (CRT) have left ventricular (LV) remodeling and improved cardiac output (CO). Effects on the systemic circulation are unknown. OBJECTIVE: To explore the effects of CRT on aortic and pulmonary blood flow and systemic afterload. METHODS: At CRT implant patients underwent a noninvasive assessment of central hemodynamics, including wave intensity analysis (n = 28). This was repeated at 6 months after CRT. A subsample (n = 11) underwent an invasive electrophysiological and hemodynamic assessment immediately following CRT. CRT response was defined as reduction in LV end-systolic volume ≥15% at 6 months. RESULTS: In CRT responders (75% of those in the noninvasive arm), there was a significant increase in CO (from 3 ± 2 L/min to 4 ± 2 L/min, P = .002) and LV dP/dtmax (from 846 ± 162 mm Hg/s to 958 ± 194 mm Hg/s, P = .001), immediately after CRT in those in the invasive arm. They demonstrated a significant increase in aortic forward compression wave (FCW) both acutely and at follow-up. The relative change in LV dP/dtmax strongly correlated with changes in the aortic FCW (R s 0.733, P = .025). CRT responders displayed a significant reduction in afterload, and a decrease in systemic vascular resistance and pulse wave velocity acutely; there was a significant decrease in acute pulmonary afterload measured by the pulmonary FCW and forward expansion wave. CONCLUSION: Improved cardiac function following CRT is attributable to a combination of changes in the cardiac and cardiovascular system. The relative importance of these 2 mechanisms may then be important for optimizing CRT.

Multipoint pacing for cardiac resynchronisation therapy in patients with heart failure: A systematic review and meta-analysis.

INTRODUCTION: Multipoint pacing (MPP) has been proposed as an effective way to improve cardiac resynchronisation therapy (CRT) response. We performed a systematic review and meta-analysis evaluating the efficacy of CRT delivered via MPP compared to conventional CRT. METHODS: A literature search was performed from inception to January 2021 for studies in Medline, Embase and Cochrane databases, comparing MPP to conventional CRT with a minimum of 6 months follow-up. Randomised and nonrandomised studies were assessed for relevant efficacy data including echocardiographic (left ventricular end systolic volume [LVESV] and ejection fraction) or functional changes (New York Heart Association [NYHA] class/Clinical Composite Score). Subgroup analyses were performed by study design and programming type. RESULTS: A total of 7 studies with a total of 1390 patients were included in the final analysis. Overall, MPP demonstrated greater echocardiographic improvement than conventional CRT in nonrandomised studies (odds ratio [OR]: 5.33, 95% confidence interval [CI]: [3.05-9.33], p < .001), however, was not significant in randomised studies (OR: 1.86, 95% CI: [0.91-3.79], p = .086). There was no significant difference in LVESV reduction >15% (OR: 1.96, 95% CI: [0.69-5.55], p = .20) or improvement by ≥1 NYHA class (OR: 2.49, 95% CI: [0.74-8.42], p = .141) when comparing MPP to conventional CRT. In a sub analysis, MPP programmed by widest anatomical separation (MPP-AS) signalled greater efficacy, however, only 120 patients were included in this analysis. CONCLUSION: Overall MPP was more efficacious in nonrandomised studies, and not superior when assessed in randomised studies. There was considerable heterogeneity in study design making overall interpretation of results challenging. Widespread MPP programming in all CRT patients is currently not justified. Further large, randomised studies with patient-specific programming may clarify its effectiveness.

Emerging evidence for a mechanistic link between low-frequency oscillation of ventricular repolarization measured from the electrocardiogram T-wave vector and arrhythmia.

Strong recent clinical evidence links the presence of prominent oscillations of ventricular repolarization in the low-frequency range (0.04-0.15 Hz) to the incidence of ventricular arrhythmia and sudden death in post-MI patients and patients with ischaemic and non-ischaemic cardiomyopathy. It has been proposed that these oscillations reflect oscillations of ventricular action potential duration at the sympathetic nerve frequency. Here we review emerging evidence to support that contention and provide insight into possible underlying mechanisms for this association.

Hospital admissions for stroke and bleeding in Hounslow following a quality improvement initiative.

OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia. Undiagnosed and poorly managed AF increases risk of stroke. The Hounslow AF quality improvement (QI) initiative was associated with improved quality of care for patients with AF through increased detection of AF and appropriate anticoagulation. This study aimed to evaluate whether there has been a change in stroke and bleeding rates in the Hounslow population following the QI initiative. METHODS: Using hospital admissions data from January 2011 to August 2018, interrupted time series analysis was performed to investigate the changes in standardised rates of admission with stroke and bleeding, following the start of the QI initiative in October 2014. RESULTS: There was a 17% decrease in the rate of admission with stroke as primary diagnosis (incidence rate ratio (IRR) 0.83; 95% CI 0.712 to 0.963; p<0.014). There was an even larger yet not statistically significant decrease in admission with stroke as primary diagnosis and AF as secondary diagnosis (IRR 0.75; 95% CI 0.550 to 1.025; p<0.071). No significant changes were observed in bleeding admissions. For each outcome, an additional regression model including both the level change and an interaction term for slope change was created. In all cases, the slope change was small and not statistically significant. CONCLUSION: Reduction in stroke admissions may be associated with the AF QI initiative. However, the immediate level change and non-significant slope change suggests a lack of effect of the intervention over time and that the decrease observed may be attributable to other events.

Late-Gadolinium Enhancement Interface Area and Electrophysiological Simulations Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy.

OBJECTIVES: This study sought to investigate whether shape-based late gadolinium enhancement (LGE) metrics and simulations of re-entrant electrical activity are associated with arrhythmic events in patients with nonischemic dilated cardiomyopathy (NIDCM). BACKGROUND: The presence of LGE predicts life-threatening ventricular arrhythmias in NIDCM; however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information. METHODS: Cardiac magnetic resonance (CMR)-LGE shape metrics were computed for a cohort of 156 patients with NIDCM and visible LGE and tested retrospectively for an association with an arrhythmic composite endpoint of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for re-entry induction in each patient's scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations. RESULTS: During a median follow-up of 1,611 (interquartile range: 881 to 2,341) days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE-myocardial interface area (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.24 to 2.47; p = 0.001), number of simulated re-entries (HR: 1.40; 95% CI: 1.23 to 1.59; p < 0.01) and LGE volume (HR: 1.44; 95% CI: 1.07 to 1.94; p = 0.02) were associated with arrhythmic events. Computational modeling revealed repolarization heterogeneity and rate-dependent block of electrical wavefronts at the LGE-myocardial interface as putative arrhythmogenic mechanisms directly related to the LGE interface area. CONCLUSIONS: The area of interface between scar and surviving myocardium, as well as simulated re-entrant activity, are associated with an elevated risk of major arrhythmic events in patients with NIDCM and LGE and represent novel risk predictors.

Assessing the ability of substrate mapping techniques to guide ventricular tachycardia ablation using computational modelling.

BACKGROUND: Identification of targets for ablation of post-infarction ventricular tachycardias (VTs) remains challenging, often requiring arrhythmia induction to delineate the reentrant circuit. This carries a risk for the patient and may not be feasible. Substrate mapping has emerged as a safer strategy to uncover arrhythmogenic regions. However, VT recurrence remains common. GOAL: To use computer simulations to assess the ability of different substrate mapping approaches to identify VT exit sites. METHODS: A 3D computational model of the porcine post-infarction heart was constructed to simulate VT and paced rhythm. Electroanatomical maps were constructed based on endocardial electrogram features and the reentry vulnerability index (RVI - a metric combining activation (AT) and repolarization timings to identify tissue susceptibility to reentry). Since scar transmurality in our model was not homogeneous, parameters derived from all signals (including dense scar regions) were used in the analysis. Potential ablation targets obtained from each electroanatomical map during pacing were compared to the exit site detected during VT mapping. RESULTS: Simulation data showed that voltage cut-offs applied to bipolar electrograms could delineate the scar, but not the VT circuit. Electrogram fractionation had the highest correlation with scar transmurality. The RVI identified regions closest to VT exit site but was outperformed by AT gradients combined with voltage cut-offs. The performance of all metrics was affected by pacing location. CONCLUSIONS: Substrate mapping could provide information about the infarct, but the directional dependency on activation should be considered. Activation-repolarization metrics have utility in safely identifying VT targets, even with non-transmural scars.

Feasibility of intraprocedural integration of cardiac CT to guide left ventricular lead implantation for CRT upgrades.

BACKGROUND: Optimal positioning of the left ventricular (LV) lead is an important determinant of cardiac resynchronization therapy (CRT) response. OBJECTIVE: Evaluate the feasibility of intraprocedural integration of cardiac computed tomography (CT) to guide LV lead implantation for CRT upgrades. METHODS: Patients undergoing LV lead upgrade underwent ECG-gated cardiac CT dyssynchrony and LV scar assessment. Target American Heart Association segment selection was determined using latest non-scarred mechanically activating segments overlaid onto real-time fluoroscopy with image co-registration to guide optimal LV lead implantation. Hemodynamic validation was performed using a pressure wire in the LV cavity (dP/dtmax) ). RESULTS: 18 patients (male 94%, 55.6% ischemic cardiomyopathy) with RV pacing burden 60.0 ± 43.7% and mean QRS duration 154 ± 30 ms underwent cardiac CT. 10/10 ischemic patients had CT evidence of scar and these segments were excluded as targets. Seventeen out of 18 (94%) patients underwent successful LV lead implantation with delivery to the CT target segment in 15 out of 18 (83%) of patients. Acute hemodynamic response (dP/dtmax ≥ 10%) was superior with LV stimulation in CT target versus nontarget segments (83.3% vs. 25.0%; p = .012). Reverse remodeling at 6 months (LV end-systolic volume improvement ≥15%) occurred in 60% of subjects (4/8 [50.0%] ischemic cardiomyopathy vs. 5/7 [71.4%] nonischemic cardiomyopathy, p = .608). CONCLUSION: Intraprocedural integration of cardiac CT to guide optimal LV lead placement is feasible with superior hemodynamics when pacing in CT target segments and favorable volumetric response rates, despite a high proportion of patients with ischemic cardiomyopathy. Multicentre, randomized controlled studies are needed to evaluate whether intraprocedural integration of cardiac CT is superior to standard care.

Economic evaluation of a dedicated cardiac resynchronisation therapy preassessment clinic.

INTRODUCTION: Patient evaluation before cardiac resynchronisation therapy (CRT) remains heterogeneous across centres and it is suspected a proportion of patients with unfavourable characteristics proceed to implantation. We developed a unique CRT preassessment clinic (CRT PAC) to act as a final review for patients already considered for CRT. We hypothesised that this clinic would identify some patients unsuitable for CRT through updated investigations and review. The purpose of this analysis was to determine whether the CRT PAC led to savings for the National Health Service (NHS). METHODS: A decision tree model was made to evaluate two clinical pathways; (1) standard of care where all patients initially seen in an outpatient cardiology clinic proceeded directly to CRT and (2) management of patients in CRT PAC. RESULTS: 244 patients were reviewed in the CRT PAC; 184 patients were eligible to proceed directly for implantation and 48 patients did not meet consensus guidelines for CRT so were not implanted. Following CRT, 82.4% of patients had improvement in their clinical composite score and 57.7% had reduction in left ventricular end-systolic volume ≥15%. Using the decision tree model, by reviewing patients in the CRT PAC, the total savings for the NHS was £966 880. Taking into consideration the additional cost of the clinic and by applying this model structure throughout the NHS, the potential savings could be as much as £39 million. CONCLUSIONS: CRT PAC appropriately selects patients and leads to substantial savings for the NHS. Adopting this clinic across the NHS has the potential to save £39 million.

High mean entropy calculated from cardiac MRI texture analysis is associated with antitachycardia pacing failure.

BACKGROUND: Antitachycardia pacing (ATP), which may avoid unnecessary implantable cardioverter-defibrillator (ICD) shocks, does not always terminate ventricular arrhythmias (VAs). Mean entropy calculated using cardiac magnetic resonance texture analysis (CMR-TA) has been shown to predict appropriate ICD therapy. We examined whether scar heterogeneity, quantified by mean entropy, is associated with ATP failure and explore potential mechanisms using computer modeling. METHODS: A subanalysis of 114 patients undergoing CMR-TA where the primary endpoint was delivery of appropriate ICD therapy (ATP or shock therapy) was performed. Patients receiving appropriate ICD therapy (n = 33) were dichotomized into "successful ATP" versus "shock therapy" groups. In silico computer modeling was used to explore underlying mechanisms. RESULTS: A total of 16 of 33 (48.5%) patients had successful ATP to terminate VA, and 17 of 33 (51.5%) patients required shock therapy. Mean entropy was significantly higher in the shock versus successful ATP group (6.1 ± 0.5 vs 5.5 ± 0.7, P = .037). Analysis of patients receiving ATP (n = 22) showed significantly higher mean entropy in the six of 22 patients that failed ATP (followed by rescue ICD shock) compared to 16 of 22 that had successful ATP (6.3 ± 0.7 vs 5.5 ± 0.7, P = .048). Computer modeling suggested inability of the paced wavefront in ATP to successfully propagate from the electrode site through patchy fibrosis as a possible mechanism of failed ATP. CONCLUSIONS: Our findings suggest lower scar heterogeneity (mean entropy) is associated with successful ATP, whereas higher scar heterogeneity is associated with more aggressive VAs unresponsive to ATP requiring shock therapy that may be due to inability of the paced wavefront to propagate through scar and terminate the VA circuit.