Optimization of anti-tachycardia pacing efficacy through scar-specific delivery and minimization of re-initiation: a virtual study on a cohort of infarcted porcine hearts.

AIMS: Anti-tachycardia pacing (ATP) is a reliable electrotherapy to painlessly terminate ventricular tachycardia (VT). However, ATP is often ineffective, particularly for fast VTs. The efficacy may be enhanced by optimized delivery closer to the re-entrant circuit driving the VT. This study aims to compare ATP efficacy for different delivery locations with respect to the re-entrant circuit, and further optimize ATP by minimizing failure through re-initiation. METHODS AND RESULTS: Seventy-three sustained VTs were induced in a cohort of seven infarcted porcine ventricular computational models, largely dominated by a single re-entrant pathway. The efficacy of burst ATP delivered from three locations proximal to the re-entrant circuit (septum) and three distal locations (lateral/posterior left ventricle) was compared. Re-initiation episodes were used to develop an algorithm utilizing correlations between successive sensed electrogram morphologies to automatically truncate ATP pulse delivery. Anti-tachycardia pacing was more efficacious at terminating slow compared with fast VTs (65 vs. 46%, P = 0.000039). A separate analysis of slow VTs showed that the efficacy was significantly higher when delivered from distal compared with proximal locations (distal 72%, proximal 59%), being reversed for fast VTs (distal 41%, proximal 51%). Application of our early termination detection algorithm (ETDA) accurately detected VT termination in 79% of re-initiated cases, improving the overall efficacy for proximal delivery with delivery inside the critical isthmus (CI) itself being overall most effective. CONCLUSION: Anti-tachycardia pacing delivery proximal to the re-entrant circuit is more effective at terminating fast VTs, but less so slow VTs, due to frequent re-initiation. Attenuating re-initiation, through ETDA, increases the efficacy of delivery within the CI for all VTs.

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.

The effect of ionizing radiation through cardiac stereotactic body radiation therapy on myocardial tissue for refractory ventricular arrhythmias: A review.

Cardiac stereotactic body radiation therapy (cSBRT) is a non-invasive treatment modality that has been recently reported as an effective treatment for ventricular arrhythmias refractory to medical therapy and catheter ablation. The approach leverages tools developed and refined in radiation oncology, where experience has been accumulated in the treatment of a wide variety of malignant conditions. However, important differences exist between rapidly dividing malignant tumor cells and fully differentiated myocytes in pathologically remodeled ventricular myocardium, which represent the respective radiation targets. Despite its initial success, little is known about the radiobiology of the anti-arrhythmic effect cSBRT. Pre-clinical data indicates a late fibrotic effect of that appears between 3 and 4 months following cSBRT, which may result in conduction slowing and block. However, there is clear clinical evidence of an anti-arrhythmic effect of cSBRT that precedes the appearance of radiation induced fibrosis for which the mechanism is unclear. In addition, the data to date suggests that even the late anti-arrhythmic effect of cSBRT is not fully attributable to radiation.-induced fibrosis. Pre-clinical data has identified upregulation of proteins expected to result in both increased cell-to-cell coupling and excitability in the early post cSBRT period and demonstrated an associated increase in myocardial conduction velocity. These observations indicate a complex response to radiotherapy and highlight the lack of clarity regarding the different stages of the anti-arrhythmic mechanism of cSBRT. It may be speculated that in the future cSBRT therapy could be planned to deliver both early and late radiation effects titrated to optimize the combined anti-arrhythmic efficacy of the treatment. In addition to these outstanding mechanistic questions, the optimal patient selection, radiation modality, radiation dose and treatment planning strategy are currently being investigated. In this review, we consider the structural and functional effect of radiation on myocardium and the possible anti-arrhythmic mechanisms of cSBRT. Review of the published data highlights the exciting prospects for the development of knowledge and understanding in this area in which so many outstanding questions exist.

Leadless left ventricular endocardial pacing for CRT upgrades in previously failed and high-risk patients in comparison with coronary sinus CRT upgrades.

AIMS: Cardiac resynchronization therapy (CRT) upgrades may be less likely to improve following intervention. Leadless left ventricular (LV) endocardial pacing has been used for patients with previously failed CRT or high-risk upgrades. We compared procedural and long-term outcomes in patients undergoing coronary sinus (CS) CRT upgrades with high-risk and previously failed CRT upgrades undergoing LV endocardial upgrades. METHOD AND RESULTS: Prospective consecutive CS upgrades between 2015 and 2019 were compared with those undergoing WiSE-CRT implantation. Cardiac resynchronization therapy response at 6 months was defined as improvement in clinical composite score (CCS) and a reduction in LV end-systolic volume (LVESV) ≥15%. A total of 225 patients were analysed; 121 CS and 104 endocardial upgrades. Patients receiving WiSE-CRT tended to have more comorbidities and were more likely to have previous cardiac surgery (30.9% vs. 16.5%; P = 0.012), hypertension (59.2% vs. 34.7%; P < 0.001), chronic obstructive airways disease (19.4% vs. 9.9%; P = 0.046), and chronic kidney disease (46.4% vs. 21.5%; P < 0.01) but similar LV ejection fraction (30.0 ± 8.3% vs. 29.5 ± 8.6%; P = 0.678). WiSE-CRT upgrades were successful in 97.1% with procedure-related mortality in 1.9%. Coronary sinus upgrades were successful in 97.5% of cases with a 2.5% rate of CS dissection and 5.6% lead malfunction/displacement. At 6 months, 91 WiSE-CRT upgrades and 107 CS upgrades had similar improvements in CCS (76.3% vs. 68.5%; P = 0.210) and reduction in LVESV ≥15% (54.2% vs. 56.3%; P = 0.835). CONCLUSION: Despite prior failed upgrades and high-risk patients with more comorbidities, WiSE-CRT upgrades had high rates of procedural success and similar improvements in CCS and LV remodelling with CS upgrades.

Clinical effectiveness of a dedicated cardiac resynchronization therapy pre-assessment clinic incorporating cardiac magnetic resonance imaging and cardiopulmonary exercise testing on patient selection and outcomes.

BACKGROUND: Pre-procedural assessment of patients undergoing cardiac resynchronization therapy (CRT) is heterogenous and patients implanted with unfavorable characteristics may account for non-response. A dedicated CRT pre-assessment clinic (CRT PAC) was developed to standardize the review process and undertake structured pre-procedural evaluation. The aim of this analysis was to determine the effectiveness on patient selection and outcomes. METHODS: A prospective database of consecutive patients attending the CRT PAC between 2013 and 2018 was analyzed. Pre-operative assessment included cardiac magnetic resonance (CMR) and cardiopulmonary exercise testing (CPET). Patients were considered CRT responders based on improvement in clinical composite score (CCS) and/or reduction in left ventricular end-systolic volume (LVESV) ≥ 15% at 6-months follow-up. RESULTS: Of 252 patients reviewed in the CRT PAC during the analysis period, 192 fulfilled consensus guidelines for implantation. Of the patients receiving CRT, 82% showed improvement in their CCS and 57% had a reduction in LVESV ≥ 15%. The presence of subendocardial scar on CMR and a peak VO2 ≤ 12 ml/kg/min on CPET predicted CRT non-response. Two patients were unsuitable for CRT as they had end-stage heart failure and died during follow-up. The majority of patients initially deemed unsuitable for CRT did not suffer from unexpected hospitalization for decompensated heart failure or died from cardiovascular disease; only 8 patients (13%) received CRT devices during follow-up because of symptomatic left ventricular systolic impairment. CONCLUSION: A dedicated CRT PAC is able to appropriately select patients for CRT. Pre-procedural investigation/imaging can identify patients unlikely to respond to, or may not yet be suitable for CRT.

Financial and resource costs of transvenous lead extraction in a high-volume lead extraction centre.

OBJECTIVES: Transvenous lead extraction (TLE) poses a significant economic and resource burden on healthcare systems; however, limited data exist on its true cost. We therefore estimate real-world healthcare reimbursement costs of TLE to the UK healthcare system at a single extraction centre. METHODS: Consecutive admissions entailing TLE at a high-volume UK centre between April 2013 and March 2018 were prospectively recorded in a computer registry. In the hospital's National Health Service (NHS) clinical coding/reimbursement database, 447 cases were identified. Mean reimbursement cost (n=445) and length of stay (n=447) were calculated. Ordinary least squares regressions estimated the relationship between cost (bed days) and clinical factors. RESULTS: Mean reimbursement cost per admission was £17 399.09±£13 966.49. Total reimbursement for all TLE admissions was £7 777 393.51. Mean length of stay was 16.3±15.16 days with a total of 7199 bed days. Implantable cardioverter-defibrillator and cardiac resynchronisation therapy defibrillator devices incurred higher reimbursement costs (70.5% and 68.7% higher, respectively, both p<0.001). Heart failure and prior valve surgery also incurred significantly higher reimbursement costs. Prior valve surgery and heart failure were associated with 8.3 (p=0.017) and 5.5 (p=0.021) additional days in hospital, respectively. CONCLUSIONS: Financial costs to the NHS from TLE are substantial. Consideration should therefore be given to cost/resource-sparing potential of leadless/extravascular cardiac devices that negate the need for TLE particularly in patients with prior valve surgery and/or heart failure. Additionally, use of antibiotic envelopes and other interventions that reduce infection risk in patients receiving transvenous leads should be considered.

Guidance for Optimal Site Selection of a Leadless Left Ventricular Endocardial Electrode Improves Acute Hemodynamic Response and Chronic Remodeling.

OBJECTIVES: This study hypothesized that guided implants, in which the optimal left ventricular endocardial (LVENDO) pacing location was identified and targeted, would improve acute markers of contractility and chronic markers of cardiac resynchronization (CRT) response. BACKGROUND: Biventricular endocardial (BiVENDO) pacing may offer a potential benefit over standard CRT; however, the optimal LVENDO pacing site is highly variable. Indiscriminately delivered BiVENDO pacing is associated with a reverse remodeling response rate of between 40% and 60%. METHODS: Registry of centers implanting a wireless, LVENDO pacing system (WiSE-CRT System, EBR Systems, Sunnyvale, California); John Radcliffe Hospital (Oxford, United Kingdom), Guy's and St. Thomas' Hospital (London, United Kingdom), and The James Cook University Hospital (Middlesbrough, United Kingdom). Centers used a combination of preprocedural imaging and electroanatomical mapping the identify the optimal LVENDO site. RESULTS: A total of 26 patients across the 3 centers underwent a guided implant. Patients were predominantly male with a mean age of 68.8 ± 8.4 years, the mean LV ejection fraction was 34.2 ± 7.8%. The mean QRS duration was 163.8 ± 26.7 ms, and 30.8% of patients had an ischemic etiology. It proved technically feasible to selectively target and deploy the pacing electrode in a chosen endocardial segment in almost all cases, with a similar complication rate to that observed during indiscriminate BiVENDO. Ninety percent of patients met the definition of echocardiographic responder. Reverse remodeling was observed in 71%. CONCLUSIONS: Guided endocardial implants were associated with a higher degree of chronic LV remodeling compared with historical nonguided approaches.

Changes in contractility determine coronary haemodynamics in dyssynchronous left ventricular heart failure, not vice versa.

BACKGROUND: Biventricular pacing has been shown to increase both cardiac contractility and coronary flow acutely but the causal relationship is unclear. We hypothesised that changes in coronary flow are secondary to changes in cardiac contractility. We sought to examine this relationship by modulating coronary flow and cardiac contractility. METHODS: Contractility and lusitropy were altered by varying the location of pacing in 8 patients. Coronary autoregulation was transiently disabled with intracoronary adenosine. Simultaneous coronary flow velocity, coronary pressure and left ventricular pressure data were measured in the different pacing settings with and without hyperaemia and wave intensity analysis performed. RESULTS: Multisite pacing was effective at altering left ventricular contractility and lusitropy (pos. dp/dtmax -13% to +10% and neg. dp/dtmax -15% to +17% compared to baseline). Intracoronary adenosine decreased microvascular resistance (362.5 mm Hg/s/m to 156.7 mm Hg/s/m, p < 0.001) and increased LAD flow velocity (22 cm/s vs 45 cm/s, p < 0.001) but did not acutely change contractility or lusitropy. The magnitude of the dominant accelerating wave, the Backward Expansion Wave, was proportional to the degree of contractility as well as lusitropy (r = 0.47, p < 0.01 and r = -0.50, p < 0.01). Perfusion efficiency (the proportion of accelerating waves) increased at hyperaemia (76% rest vs 81% hyperaemia, p = 0.04). Perfusion efficiency correlated with contractility and lusitropy at rest (r = 0.43 & -0.50 respectively, p = 0.01) and hyperaemia (r = 0.59 & -0.6, p < 0.01). CONCLUSIONS: Acutely increasing coronary flow with adenosine in patients with systolic heart failure does not increase contractility. Changes in coronary flow with biventricular pacing are likely to be a consequence of enhanced cardiac contractility from resynchronization and not vice versa.

3D/2D model-to-image registration by imitation learning for cardiac procedures.

PURPOSE: In cardiac interventions, such as cardiac resynchronization therapy (CRT), image guidance can be enhanced by involving preoperative models. Multimodality 3D/2D registration for image guidance, however, remains a significant research challenge for fundamentally different image data, i.e., MR to X-ray. Registration methods must account for differences in intensity, contrast levels, resolution, dimensionality, field of view. Furthermore, same anatomical structures may not be visible in both modalities. Current approaches have focused on developing modality-specific solutions for individual clinical use cases, by introducing constraints, or identifying cross-modality information manually. Machine learning approaches have the potential to create more general registration platforms. However, training image to image methods would require large multimodal datasets and ground truth for each target application. METHODS: This paper proposes a model-to-image registration approach instead, because it is common in image-guided interventions to create anatomical models for diagnosis, planning or guidance prior to procedures. An imitation learning-based method, trained on 702 datasets, is used to register preoperative models to intraoperative X-ray images. RESULTS: Accuracy is demonstrated on cardiac models and artificial X-rays generated from CTs. The registration error was [Formula: see text] on 1000 test cases, superior to that of manual ([Formula: see text]) and gradient-based ([Formula: see text]) registration. High robustness is shown in 19 clinical CRT cases. CONCLUSION: Besides the proposed methods feasibility in a clinical environment, evaluation has shown good accuracy and high robustness indicating that it could be applied in image-guided interventions.

LV function validation of computer-assisted interventional system for cardiac resyncronisation therapy.

PURPOSE: Cardiac resynchronisation therapy (CRT) is an established treatment for symptomatic patients with heart failure, a prolonged QRS duration, and impaired left ventricular (LV) function; however, non-response rates remain high. Recently proposed computer-assisted interventional platforms for CRT provide new routes to improving outcomes. Interventional systems must process information in an accurate, fast and highly automated way that is easy for the interventional cardiologists to use. In this paper, an interventional CRT platform is validated against two offline diagnostic tools to demonstrate that accurate information processing is possible in the time critical interventional setting. METHODS: The study consisted of 3 healthy volunteers and 16 patients with heart failure and conventional criteria for CRT. Data analysis included the calculation of end-diastolic volume, end-systolic volume, stroke volume and ejection fraction; computation of global volume over the cardiac cycle as well as time to maximal contraction expressed as a percentage of the total cardiac cycle. RESULTS: The results showed excellent correlation ([Formula: see text] values of [Formula: see text] and Pearson correlation coefficient of [Formula: see text]) with comparable offline diagnostic tools. CONCLUSION: Results confirm that our interventional system has good accuracy in everyday clinical practice and can be of clinical utility in identification of CRT responders and LV function assessment.

Investigating a Novel Activation-Repolarisation Time Metric to Predict Localised Vulnerability to Reentry Using Computational Modelling.

Exit sites associated with scar-related reentrant arrhythmias represent important targets for catheter ablation therapy. However, their accurate location in a safe and robust manner remains a significant clinical challenge. We recently proposed a novel quantitative metric (termed the Reentry Vulnerability Index, RVI) to determine the difference between activation and repolarisation intervals measured from pairs of spatial locations during premature stimulation to accurately locate the critical site of reentry formation. In the clinic, the method showed potential to identify regions of low RVI corresponding to areas vulnerable to reentry, subsequently identified as ventricular tachycardia (VT) circuit exit sites. Here, we perform an in silico investigation of the RVI metric in order to aid the acquisition and interpretation of RVI maps and optimise its future usage within the clinic. Within idealised 2D sheet models we show that the RVI produces lower values under correspondingly more arrhythmogenic conditions, with even low resolution (8 mm electrode separation) recordings still able to locate vulnerable regions. When applied to models of infarct scars, the surface RVI maps successfully identified exit sites of the reentrant circuit, even in scenarios where the scar was wholly intramural. Within highly complex infarct scar anatomies with multiple reentrant pathways, the identified exit sites were dependent upon the specific pacing location used to compute the endocardial RVI maps. However, simulated ablation of these sites successfully prevented the reentry re-initiation. We conclude that endocardial surface RVI maps are able to successfully locate regions vulnerable to reentry corresponding to critical exit sites during sustained scar-related VT. The method is robust against highly complex and intramural scar anatomies and low resolution clinical data acquisition. Optimal location of all relevant sites requires RVI maps to be computed from multiple pacing locations.

Contribution of PET Imaging to the Diagnosis of Septic Embolism in Patients With Pacing Lead Endocarditis.

OBJECTIVES: The aim of this study was to investigate the role of 18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scanning in identifying septic embolism in patients with lead endocarditis. BACKGROUND: Lead endocarditis may be associated with septic embolism, in which case the administration mode, type, and duration of antibiotic therapy must be adapted. However, diagnosis can be challenging: magnetic resonance imaging (MRI) cannot be performed in the vast majority of patients with cardiac implantable electronic devices (CIEDs). FDG PET/CT scanning has been proposed as a diagnostic tool for suspected CIED infection. METHODS: Thirty-five consecutive patients with lead endocarditis were prospectively studied. FDG PET/CT scanning was performed and analyzed blindly by experienced nuclear medicine physicians to assess for the presence of septic embolism 2 days before lead extraction. RESULTS: FDG PET/CT scanning identified septic emboli in 10 patients (29%): 7 with spondylodiscitis, 2 with septic pulmonary emboli, and 1 with an infected vascular prosthesis. Among the 7 patients with occult spondylodiscitis, 4 were asymptomatic, and 3 had back pain with negative CT imaging, MRI being contraindicated due to non MRI-compatible CIEDs. Antimicrobial therapy was adapted (double antibiotic therapy with good bone penetration) and prolonged. Among other important ancillary findings, 3 patients presented focal FDG uptake in the colon (1 adenocarcinoma, and 2 resected polyps) and 2 in the esophagus (both cases confirmed as neoplasia). CONCLUSIONS: This study emphasizes the potential utility of FDG PET/CT scanning as a diagnostic tool for septic emboli in patients with pacing lead endocarditis. This promising diagnostic tool may be integrated in the diagnostic algorithm of patients with lead endocarditis because diagnosis of septic embolisms has a direct and significant impact on the therapeutic care pathway.

Extraction of chronic pacemaker and defibrillator leads from the coronary sinus: laser infrequently used but required.

AIMS: Cardiac resynchronization therapy is an accepted treatment for heart failure but it may be necessary to explant these systems along with their leads. The evidence base for coronary sinus (CS) lead extractions is limited. We aimed to evaluate the percutaneous removal of these leads and the utility of laser extraction when necessary. METHODS AND RESULTS: Of 265 patients referred for lead extraction between January 2004 and June 2008, 32 (12.1%) involved CS leads (30 males, mean age 67 years). Mean implantation time was 26.5 +/- 28.7 months (range 1-116 months). Indications for extraction were pocket infection (34.4%), lead malfunction (43.8%), skin erosion (15.6%), and endocarditis (6.2%). Twenty-eight (87.5%) CS leads were removed with manual traction, with laser utilized in four cases (12.5%). No major complications of CS laceration, pericardial effusion, emergency surgery, or death occurred. CONCLUSION: Our experience supports the percutaneous extraction of CS leads as a safe and effective procedure including the utility of laser when necessary.

Treatment of left-sided prosthetic valve thrombosis: thrombolysis or surgery?

Although, traditionally, surgery has been the treatment of choice for left-sided prosthetic valve thrombosis (PVT), there are significant risks associated with re-do surgery. Thrombolysis is an alternative to surgery and has a success rate in excess of 80%, but is associated with an -10% risk of systemic embolism and a 7% mortality rate. Guidelines for the use of thrombolytic therapy for PVT were produced using data acquired from older valves, and largely without the use of transesophageal echocardiography (TEE). Data from more recent studies suggest that thrombolysis should be regarded as first-line therapy for PVT in all NYHA classes. The use of TEE is recommended to visualize thrombus in suspected cases.