Enhancing transvenous lead extraction risk prediction: Integrating imaging biomarkers into machine learning models.

BACKGROUND: Machine learning (ML) models have been proposed to predict risk related to transvenous lead extraction (TLE). OBJECTIVE: The purpose of this study was to test whether integrating imaging data into an existing ML model increases its ability to predict major adverse events (MAEs; procedure-related major complications and procedure-related deaths) and lengthy procedures (≥100 minutes). METHODS: We hypothesized certain features-(1) lead angulation, (2) coil percentage inside the superior vena cava (SVC), and (3) number of overlapping leads in the SVC-detected from a pre-TLE plain anteroposterior chest radiograph (CXR) would improve prediction of MAE and long procedural times. A deep-learning convolutional neural network was developed to automatically detect these CXR features. RESULTS: A total of 1050 cases were included, with 24 MAEs (2.3%) . The neural network was able to detect (1) heart border with 100% accuracy; (2) coils with 98% accuracy; and (3) acute angle in the right ventricle and SVC with 91% and 70% accuracy, respectively. The following features significantly improved MAE prediction: (1) ≥50% coil within the SVC; (2) ≥2 overlapping leads in the SVC; and (3) acute lead angulation. Balanced accuracy (0.74-0.87), sensitivity (68%-83%), specificity (72%-91%), and area under the curve (AUC) (0.767-0.962) all improved with imaging biomarkers. Prediction of lengthy procedures also improved: balanced accuracy (0.76-0.86), sensitivity (75%-85%), specificity (63%-87%), and AUC (0.684-0.913). CONCLUSION: Risk prediction tools integrating imaging biomarkers significantly increases the ability of ML models to predict risk of MAE and long procedural time related to TLE.

Long-term survival following transvenous lead extraction: unpicking differences according to sex.

AIMS: Female sex is a recognized risk factor for procedure-related major complications including in-hospital mortality following transvenous lead extraction (TLE). Long-term outcomes following TLE stratified by sex are unclear. The purpose of this study was to evaluate factors influencing long-term survival in patients undergoing TLE according to sex. METHODS AND RESULTS: Clinical data from consecutive patients undergoing TLE in the reference centre between 2000 and 2019 were prospectively collected. The total cohort was divided into groups based on sex. We evaluated the association of demographic, clinical, device-related, and procedure-related factors on long-term mortality. A total of 1151 patients were included, with mean 66-month follow-up and mortality of 34.2% (n = 392). The majority of patients were male (n = 834, 72.4%) and 312 (37.4%) died. Males were more likely to die on follow-up [hazard ratio (HR) = 1.58 (1.23-2.02), P < 0.001]. Males had a higher mean age at explant (66.2 ± 13.9 vs. 61.3 ± 16.3 years, P < 0.001), greater mean co-morbidity burden (2.14 vs. 1.27, P < 0.001), and lower mean left ventricular ejection fraction (LVEF) (43.4 ± 14.0 vs. 50.8 ± 12.7, P = 0.001). For the female cohort, age > 75 years [HR = 3.45 (1.99-5.96), P < 0.001], estimated glomerular filtration rate < 60 [HR = 1.80 (1.03-3.11), P = 0.037], increasing co-morbidities (HR = 1.29 (1.06-1.56), P = 0.011), and LVEF per percentage increase [HR = 0.97 (0.95-0.99), P = 0.005] were all significant factors predicting mortality. The same factors influenced mortality in the male cohort; however, the HRs were lower. CONCLUSION: Female patients undergoing TLE have more favourable long-term outcomes than males with lower long-term mortality. Similar factors influenced mortality in both groups.

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.

The role of guidance in delivering cardiac resynchronization therapy: A systematic review and network meta-analysis.

Background: Positioning the left ventricular lead at the optimal myocardial segment has been proposed to improve cardiac resynchronization therapy (CRT) response. Objectives: We performed a systematic review and network meta-analysis evaluating echocardiographic and clinical response delivered with different guidance modalities compared to conventional fluoroscopic positioning. Methods: Randomized trials with ≥6 months follow-up comparing any combination of imaging, electrical, hemodynamic, or fluoroscopic guidance were included. Imaging modalities were split whether one modality was used: cardiac magnetic resonance (CMR), speckle-tracking echocardiography (STE), single-photon emission computed tomography, cardiac computed tomography (CT), or a combination of these, defined as "multimodality imaging." Results: Twelve studies were included (n = 1864). Pair-wise meta-analysis resulted in significant odds of reduction in left ventricular end-systolic volume (LVESV) >15% (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.05-2.13, P = .025) and absolute reduction in LVESV (standardized mean difference [SMD] -0.25, 95% CI -0.43 to -0.08, P = .005) with guidance. CMR (OR 55.3, 95% CI 4.7-656.9, P = .002), electrical (OR 17.0, 95% CI 2.9-100, P = .002), multimodality imaging (OR 4.47, 95% CI 1.36-14.7, P = .014), and hemodynamic guidance (OR 1.29-28.0, P = .02) were significant in reducing LVESV >15%. Only STE demonstrated a significant reduction in absolute LVESV (SMD -0.38, 95% CI -0.68 to -0.09, P = .011]. CMR had the highest probability of improving clinical response (OR 17.9, 95% CI 5.14-62.5, P < .001). Conclusion: Overall, guidance improves CRT outcomes. STE and multimodality imaging provided the most reliable evidence of efficacy. Wide CIs observed for results of CMR guidance suggest more powered studies are required before a clear ranking is possible.

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.

Feasibility of leadless left ventricular septal pacing with the WiSE-CRT system to target the left bundle branch area: A porcine model and multicenter patient experience.

BACKGROUND: The WiSE-CRT system delivers leadless endocardial left ventricular (LV) pacing to achieve cardiac resynchronization therapy. The electrode is conventionally placed on the lateral wall, but implanting on the LV septum may have advantages, including capture of the left bundle branch, and improved battery longevity owing to reduced distance from the transmitter. OBJECTIVE: The purpose of this study was to assess the feasibility of leadless LV septal pacing via the WiSE-CRT system. METHODS: Two pigs underwent electrode implantation on the LV septum with subsequent anatomical and histological examination. Eight patients underwent implantation of the WiSE-CRT system with deployment of the electrode on the LV septum via an interatrial transseptal approach. RESULTS: Deployment of the electrode on the LV septum was successful in both animals. Histological examination demonstrated electrode tines in close proximity to Purkinje tissue. WiSE-CRT implantation with an LV septal electrode was successful in all patients. Biventricular capture was confirmed, with a significant reduction in QRS duration (187.1 ± 33.8 ms vs 149.5 ± 15.7 ms; P = .009). Temporary LV pacing achieved further QRS reduction (139.8 ± 12.4 ms), and in 4 patients the peak LV activation time in lead V5/V6 was <90 ms, suggesting left bundle branch capture. At early follow-up, the median LV pacing percentage was 98.5% and 5 patients (62.5%) improved symptomatically. The transmitter-to-electrode distance was lower than the distance to the lateral wall during acoustic window screening (8.8 ± 1.6 cm vs 11.9 ± 1.5 cm; P = .002). CONCLUSION: Leadless LV septal pacing with the WiSE-CRT system to target the left bundle branch appears feasible. Further study is required to assess the efficacy and safety of this technique.

Pacing Optimized by Left Ventricular dP/dtmax.

Left ventricular (LV) dP/dtmax provides a sensitive measure of the acute hemodynamic response to cardiac resynchronization therapy (CRT) and can predict reverse remodeling on echocardiography. Its use to guide LV lead placement has been shown to improve outcomes in a multicenter randomized trial. Given the invasive protocol required for measurement, it is unlikely to be universally beneficial for patients undergoing CRT but may be useful for patients who do not respond to conventional CRT, or in those who have borderline indications or risk factors for non-response. In such cases, LV dP/dtmax may help guide LV lead placement, optimize device programming, and select the best alternative method of delivering CRT, such endocardial LV pacing or conduction system pacing.

Effect of scar and pacing location on repolarization in a porcine myocardial infarction model.

Background: The effect of chronic ischemic scar on repolarization is unclear, with conflicting results from human and animal studies. An improved understanding of electrical remodeling within scar and border zone tissue may enhance substrate-guided ablation techniques for treatment of ventricular tachycardia. Computational modeling studies have suggested increased dispersion of repolarization during epicardial, but not endocardial, left ventricular pacing, in close proximity to scar. However, the effect of endocardial pacing near scar in vivo is unknown. Objective: The purpose of this study was to investigate the effect of scar and pacing location on local repolarization in a porcine myocardial infarction model. Methods: Six model pigs underwent late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging followed by electroanatomic mapping of the left ventricular endocardium. LGE-CMR images were registered to the anatomic shell and scar defined by LGE. Activation recovery intervals (ARIs), a surrogate for action potential duration, and local ARI gradients were calculated from unipolar electrograms within areas of late gadolinium enhancement (aLGE) and healthy myocardium. Results: There was no significant difference between aLGE and healthy myocardium in mean ARI (304.20 ± 19.44 ms vs 300.59 ± 19.22 ms; P = .43), ARI heterogeneity (23.32 ± 11.43 ms vs 24.85 ± 12.99 ms; P = .54), or ARI gradients (6.18 ± 2.09 vs 5.66 ± 2.32 ms/mm; P = .39). Endocardial pacing distance from scar did not affect ARI gradients. Conclusion: Our findings suggest that changes in ARI are not an intrinsic property of surviving myocytes within scar, and endocardial pacing close to scar does not affect local repolarization.

Machine learning-derived major adverse event prediction of patients undergoing transvenous lead extraction: Using the ESC EHRA EORP European lead extraction ConTRolled ELECTRa registry.

BACKGROUND: Transvenous lead extraction (TLE) remains a high-risk procedure. OBJECTIVE: The purpose of this study was to develop a machine learning (ML)-based risk stratification system to predict the risk of major adverse events (MAEs) after TLE. A MAE was defined as procedure-related major complication and procedure-related death. METHODS: We designed and evaluated an ML-based risk stratification system trained using the European Lead Extraction ConTRolled (ELECTRa) registry to predict the risk of MAEs in 3555 patients undergoing TLE and tested this on an independent registry of 1171 patients. ML models were developed, including a self-normalizing neural network (SNN), stepwise logistic regression model ("stepwise model"), support vector machines, and random forest model. These were compared with the ELECTRa Registry Outcome Score (EROS) for MAEs. RESULTS: There were 53 MAEs (1.7%) in the training cohort and 24 (2.4%) in the test cohort. Thirty-two clinically important features were used to train the models. ML techniques were similar to EROS by balanced accuracy (stepwise model: 0.74 vs EROS: 0.70) and superior by area under the curve (support vector machines: 0.764 vs EROS: 0.677). The SNN provided a finite risk for MAE and accurately identified MAE in 14 of 169 "high (>80%) risk" patients (8.3%) and no MAEs in all 198 "low (<20%) risk" patients (100%). CONCLUSION: ML models incrementally improved risk prediction for identifying those at risk of MAEs. The SNN has the additional advantage of providing a personalized finite risk assessment for patients. This may aid patient decision making and allow better preoperative risk assessment and resource allocation.

Dispersion of repolarization increases with cardiac resynchronization therapy and is associated with left ventricular reverse remodeling.

PURPOSE: Cardiac resynchronization therapy (CRT) reduces ventricular activation times and electrical dyssynchrony, however the effect on repolarization is unclear. In this study, we sought to investigate the effect of CRT and left ventricular (LV) remodeling on dispersion of repolarization using electrocardiographic imaging (ECGi). METHODS: 11 patients with heart failure and electrical dyssynchrony underwent ECGi 1-day and 6-months post CRT. Reconstructed epicardial electrograms were used to create maps of activation time, repolarization time (RT) and activation recovery intervals (ARI) and calculate measures of RT, ARI and their dispersion. ARI was corrected for heart rate (cARI). RESULTS: Compared to baseline rhythm, LV cARI dispersion was significantly higher at 6 months (28.2 ± 7.7 vs 36.4 ± 7.2 ms; P = 0.03) but not after 1 day (28.2 ± 7.7 vs 34.4 ± 6.8 ms; P = 0.12). There were no significant differences from baseline to CRT for mean LV cARI or RT metrics. Significant LV remodeling (>15% reduction in end-systolic volume) was an independent predictor of increase in LV cARI dispersion (P = 0.04) and there was a moderate correlation between the degree of LV remodeling and the relative increase in LV cARI dispersion (R = -0.49) though this was not statistically significant (P = 0.12). CONCLUSION: CRT increases LV cARI dispersion, but this change was not fully apparent until 6 months post implant. The effects of CRT on LV cARI dispersion appeared to be dependent on LV reverse remodeling, which is in keeping with evidence that the risk of ventricular arrhythmia after CRT is higher in non-responders compared to responders.

Rate or Rhythm Control in CRT (RHYTHMIC): Study rationale and protocol.

Background: Atrial fibrillation (AF) has several detrimental effects on heart failure patients treated with cardiac resynchronization therapy (CRT). These include suboptimal biventricular pacing and the loss of atrioventricular (AV) synchrony. AV node ablation improves biventricular pacing and clinical outcomes in large observational studies. However, restoration of sinus rhythm with AF ablation may have additional benefits. Objectives: To compare the effects of AV node ablation and AF ablation on echocardiographic and symptomatic outcomes in patients with CRT and suboptimal biventricular pacing. Methods: RHYTHMIC is a multicenter prospective randomized controlled trial. Seventy patients will be recruited and randomized to each ablation strategy in a 1:1 ratio. Key inclusion criteria include a previous CRT implant (with atrial lead) for dyssynchronous heart failure, and biventricular pacing <95% secondary to AF. Patients with permanent AF will be excluded. Results: Patients will undergo baseline assessment including transthoracic echocardiography (TTE), device check, blood tests, electrocardiogram (ECG), 6-minute walk test, and symptom questionnaire. They will then undergo either AV node ablation or AF ablation according to their allocated group. Follow-up will occur at 1 week (TTE and ECG) and at 6 months (repeat of baseline investigations). The primary endpoint will be change in left ventricular ejection fraction on TTE. Conclusion: This is the first randomized controlled trial comparing AV node ablation and AF ablation in patients with CRT. We anticipate it will provide valuable insight into the management of this frequently encountered clinical scenario in a challenging patient cohort.

Technical feasibility of leadless left bundle branch area pacing for cardiac resynchronization: a case series.

BACKGROUND: Left bundle branch area pacing (LBBAP) is a novel form of conduction system pacing which can reverse left bundle branch block and deliver cardiac resynchronization therapy (CRT). The WiSE-CRT system delivers leadless endocardial pacing with symptomatic and left ventricular (LV) remodelling improvements following intervention. We report the technical feasibility of delivering leadless LBBAP using the WiSE-CRT system. CASE SUMMARY: In Case 1, a 57-year-old male with ischaemic cardiomyopathy and complete heart block underwent implantation of the WiSE-CRT system, using a retrograde transaortic approach, after failed conventional CRT. Temporary left bundle stimulation from the LV septum achieved superior electrical resynchronization and equivalent haemodynamic response compared to endocardial pacing at the lateral LV wall. In Case 2, an 82-year-old gentleman with tachyarrhythmia-induced cardiomyopathy underwent WiSE-CRT implantation via a trans-septal inter-atrial approach, with the endocardial electrode successfully deployed in the LV septum. DISCUSSION: Here we report the first case of deployment of the WiSE-CRT endocardial electrode in the LV septum and demonstrate the technical feasibility of leadless LBBAP. Entirely leadless CRT is an attractive option for patients with venous access issues or recurrent lead complications and has previously been successful using the WiSE-CRT system and a leadless pacemaker in the right ventricle. Further studies are required to assess long-term efficacy and safety of leadless LBBAP.

Endocardial left ventricular pacing.

Cardiac resynchronization therapy (CRT) is an effective treatment for dyssynchronous heart failure; however, 30-50% of patients fail to improve after implant. Endocardial left ventricular (LV) pacing is an alternative therapy for patients who do not respond to conventional CRT or in whom placement of a lead via the coronary sinus is not possible. It enables pacing at a wide variety of sites, without restrictions due to coronary sinus anatomy, and there is evidence of superior electrical resynchronization and hemodynamic response compared with conventional epicardial CRT. In this article, we discuss the potential advantages and disadvantages of endocardial LV pacing compared with conventional CRT, review the evidence for the delivery of endocardial LV pacing using both lead-based and leadless systems, and explore possible future directions of this novel technology.

Comparison of electrical dyssynchrony parameters between electrocardiographic imaging and a simulated ECG belt.

AIMS: Electrocardiographic imaging (ECGi) and the ECG belt are body surface potential mapping systems which can assess electrical dyssynchrony in patients undergoing cardiac resynchronization therapy (CRT). ECGi-derived dyssynchrony metrics are calculated from reconstructed epicardial potentials based on body surface potentials combined with a thoracic CT scan, while the ECG belt relies on body surface potentials alone. The relationship between dyssynchrony metrics from these two systems is unknown. In this study we aim to compare intra-ventricular and inter-ventricular dyssynchrony metrics between ECGi and the ECG belt. METHODS: Seventeen patients underwent ECGi after CRT. A subsample of 40 body surface potentials was used to simulate the ECG belt. ECGi dyssynchrony metrics, calculated from reconstructed epicardial potentials, and ECG belt dyssynchrony metrics, calculated from the sampled body surface potentials were compared. RESULTS: There was a strong positive correlation between ECGi left ventricular activation time (LVAT) and ECG belt left thorax activation time (LTAT) (R = 0.88 ; P < 0.001) and between ECGi standard deviation of activation times (SDAT) and ECG belt-SDAT (R = 0.76; P < 0.001) during intrinsic rhythm. The correlation for both pairs was also strong during biventricular pacing. Ventricular electrical uncoupling, a well validated ECGi inter-ventricular dyssynchrony metric, correlated strongly with ECG belt-SDAT during intrinsic rhythm (R = 0.76; P < 0.001) but not biventricular pacing (R = 0.29; P = 0.26). Cranial or caudal displacement of the simulated ECG belt did not affect LTAT or SDAT. CONCLUSION: ECGi- and ECG belt-derived intra-ventricular and inter-ventricular dyssynchrony metrics were strongly correlated. The ECG belt may offer comparable dyssynchrony assessment to ECGi, with associated practical and cost advantages.

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.