Ventricular Activation Research Articles

Abstract 4138640: Learning Curve for Left Bundle Branch Area Pacing Lead Implantation

Background: Left bundle branch area pacing (LBBAP) has shown promising outcomes at experienced centers, but less is known about the learning curve with new adoption of LBBAP. We conducted a retrospective analysis (2020-2023) of the learning curve for LBBAP at our center. Methods: Procedural success and complications in adult patients undergoing LBBAP by operators with >5-years’ experience in device implantation were compared between operators’ experience ≤10th (LBBAP inexp ) vs. >10th (LBBAP exp ) LBBAP implant. Successful LBBAP was defined as left ventricular activation time (LVAT) ≤80 ms. Results: Seven operators implanted LBBAP in 288 patients (age 73±11 years, 38% women): 68 (24%) in LBBAP inexp vs. 220 (76%) patients in LBBAP exp groups with similar baseline characteristics (all p >0.05). The median number of implants per operator was 22 (range 8-83). Table 1 shows the procedural characteristics and ECG results. Post-implant LVAT ≤80 ms was less frequent in LBBAP inexp compared to LBBAP exp (56.9% vs 72.4%, p=0.04, Figure 1 ). There were no differences in paced QRS duration ≤130 ms (75.9% vs. 76.1 %, p=1.0) or operator self-identified success (85% vs. 91%, p=0.2). With new single-/dual-chamber device implants, there was no difference in implant duration (103.4±31.8 vs. 101.6±38.5 minutes, p=0.3) but there was longer fluoroscopy in LBBAP inexp (12.6±10.1 vs. 8.2±8.0 minutes, p<0.0001, Figure 1 ). The average number of attempts at LBBAP was lower in LBBAP inexp vs. LBBAP exp (2.0 ± 1.5 vs. 2.9 ± 2.9, p=0.03). There was no difference in complications between the 2 groups ( Table 2 ). Conclusion: Operators use less fluoroscopy, make more attempts at LBBAP and more frequently achieve LVAT ≤80 ms after their first 10 implants.

Machine Learning Identifies Arrhythmogenic Features of QRS Fragmentation in Human Cardiomyopathy: Implications for Improving Risk Stratification

Heterogeneous ventricular activation can provide the substrate for ventricular arrhythmias (VA), but its manifestation on the ECG as a risk stratifier is not well-defined. To characterize the spatiotemporal features of QRS peaks that best predict VA in patients with cardiomyopathy (CM) using machine learning (ML). Prospectively enrolled CM patients with prophylactic defibrillators (n=95) underwent digital, high-resolution ECG recordings during intrinsic rhythm and ventricular pacing at 100-120bpm. Intra QRS peaks in the signal-averaged precordial leads were identified and their characteristics (amplitude, width and timing within the QRS) were transformed into 4-bin histograms. Random forest models of these characteristics in each lead alongside clinical data were trained on 76 patients and tested on 19 patients with cross-validation to determine the features that predicted VA. Patients were followed for 45 (22-48) months and 21% had VA. The individual ML models determined (AUROC) intrinsic QRS peak amplitude (0.88), width (0.78) and location (0.84) to all predict VA. In a combined model including all QRS peak characteristics, peaks with amplitude <31uV in V1, a width 4-8ms in V1, and location in the final quarter of the QRS of V1 were most predictive. Neither clinical data nor QRS peak characteristics assessed during ventricular pacing improved VA prediction when combined with intrinsic QRS peak characteristics. Arrhythmogenic QRS fragmentation is characterized by narrow, low-amplitude peaks in the terminal QRS of lead V1. These features alone without clinical variables or ventricular pacing are sufficient to accurately risk stratify CM patients.

BOATMAP: Bayesian Optimization Active Targeting for Monomorphic Arrhythmia Pace-mapping

Recent advances in machine learning and deep learning have presented new opportunities for learning to localize the origin of ventricular activation from 12-lead electrocardiograms (ECGs), an important step in guiding ablation therapies for ventricular tachycardia. Passively learning from population data is faced with challenges due to significant variations among subjects, and building a patient-specific model raises the open question of where to select pace-mapping data for training. This work introduces BOATMAP, a novel active learning approach designed to provide clinicians with interpretable guidance that progressively assists in locating the origin of ventricular activation from 12-lead ECGs. BOATMAP inverts the input–output relationship in traditional machine learning solutions to this problem and learns the similarity between a target ECG and a paced ECG as a function of the pacing site coordinates. Using Gaussian processes (GP) as a surrogate model, BOATMAP iteratively refines the estimated similarity landscape while providing suggestions to clinicians regarding the next optimal pacing site. Furthermore, it can incorporate constraints to avoid suggesting pacing in non-viable regions such as the core of the myocardial scar. Tested in a realistic simulation environment in various heart geometries and tissue properties, BOATMAP demonstrated the ability to accurately localize the origin of activation, achieving an average localization accuracy of 3.9±3.6mm with only 8.0±4.0 pacing sites. BOATMAP offers real-time interpretable guidance for accurate localization and enhancing clinical decision-making.

Fibroblast activation in cardio-oncology

Abstract Introduction Carcinoid heart disease is a rare disease affecting the right sided heart valves (1) while anthracycline cardiotoxicity is a dreaded sequelae of a common chemotherapeutic agent that can occur early or even years after exposure (2). Activated fibroblasts, a key factor in these diseases, can be imaged with 68Gallium-fibroblast activation protein inhibitor (68Ga-FAPI). Method 12 patients with carcinoid syndrome, 12 patients with previous anthracycline exposure and 10 healthy volunteers underwent hybrid 68Ga-FAPI positron emission tomography and magnetic resonance imaging. Areas of fibroblast activation were quantified as mean and maximum target-to-background ratios (TBRmean and TBRmax). Results Carcinoid syndrome: 2 of the 12 patients had carcinoid heart disease [mean age 70, 50% female] (CHD) (Figure 1A). 68Ga-FAPI uptake was seen in the liver lesions of all patients with known carcinoid liver tumours. Of the 10 patients without cardiac involvement, 6 had significant tricuspid valve 68Ga-FAPI uptake (CHD- FAPI+) (Figure 1B) and 4 did not (CHD- FAPI-). Median tricuspid TBRmax was significantly higher in CHD + [2.38 (IQR 2.35-2.42)], than CHD- patients [CHD- FAPI+: 1.68 (IQR 1.65-1.73), CHD- FAPI-: 1.55 (IQR 1.53-1.65)], although this was higher than healthy volunteers [1.45 (IQR 1.43- 1.61; p&amp;lt;0.05). CHD- FAPI+ patients had significantly elevated urinary 5-HIAA levels compared to CHD- FAPI- patients [Median =188 mg/24hr (IQR 151-196) in CHD- FAPI+ vs 32mg/24hr ( IQR 12-73); p=0.03]. Anthracycline chemotherapy: 3 of the 12 patients had cardiotoxicity [mean age 61, 67% female]. Anthracycline patients had higher left ventricular myocardial 68Ga-FAPI uptake than healthy volunteers with cardiotoxicity patients having the highest. [TBRmean: Cardiotoxicity 1.46 (IQR 1.36- 1.53), No cardiotoxicity 1.37 (IQR 1.19- 1.49), Healthy volunteers 0.73 (IQR 0.66 - 0.81); p&amp;lt;0.01 (Figure 1E). Across the cohort a moderate negative correlation was observed between Left ventricular ejection fraction and 68Ga-FAPI activity (LV TBRmean r =-0.46 and TBRmax (r= -0.66) Discussion 68 Ga-FAPI provides us the ability to assess fibroblast activation and for the first time demonstrated the key role of these cells in both these cardio-oncology conditions. Increased fibroblast activation is observed around the tricuspid valve in patients with carcinoid syndrome both in those with and without overt clinical disease. Similarly increased myocardial fibroblast activation is observed in patients exposed to anthracyclines even many years after exposure and where there is no overt evidence of cardiotoxicity. Conclusion 68Ga-FAPI imaging holds promise in evaluating the role of activated fibroblasts in the pathology of both carcinoid heart disease and cardiotoxicity, providing information beyond the current resolution of current clinical approaches.

Prolonged ventricular activation time as a novel biomarker identifying burn-out phase of hypertrophic cardiomyopathy

Abstract Background Patients with hypertrophic cardiomyopathy (HCM) classically have preserved systolic function and decreased left ventricular end-diastolic volume. However, in a small sub-population, patients paradoxically develop systolic dysfunction, left ventricular dilatation, and ventricular wall thinning, which is known as end-stage hypertrophic cardiomyopathy or "burned-out cardiomyopathy’. Although an electrocardiogram (ECG) is a pivotal tool in HCM, its role in the detection of burned-out HCM has not been investigated. Purpose We assessed the ventricular activation time (VAT), an ECG marker of the duration of ventricular depolarization, as a predictive tool in the detection of the HCM burn-out phase. Methods We prospectively studied consecutive patients diagnosed with HCM via echocardiography at our medical center between 2017 and 2022. The ECG, along with echocardiography, was performed on the same day as the diagnosis. VAT was measured in milliseconds between the onset of the QRS complex to the peak or R wave on the V5 and V6 precordial ECG lead. HCM burn-out phase was supported when the left ventricular ejection fraction (LVEF) was below 50%, measured with echocardiography. Statistical analysis was performed using the SPSS software. Results Forty-five patients with HCM were studied, and their mean age was 51, while 78% (35/45) were male. Echocardiography data upon diagnosis revealed a mean maximum wall thickness of 19 (±3mm) and a mean left ventricular ejection fraction of 65% (±5%). Left ventricular outflow obstruction was present in 31% (14/45). During the study, 24% (11/45) presented atrial fibrillation, 44% (20/45) had an ICD implantation, and 22% (10/45) progressed to the burn-out phase of HCM. HCM patients who presented atrial fibrillation (63±31 vs. 46±14msec, p=0.018) or burn-out phase (65±32 vs. 46±13msec, p=0,009) had a significantly higher VAT than those subsets without. Notably, there was a significant positive relationship between VAT a burn-out phenotype (r=0,385, p=0.009). HCM patients with greater VAT also had a significantly higher risk of presenting a larger left atrial diameter (r=0,295, p=0.048), an increased left ventricular end-diastolic diameter (r=0.306, p=0.041), and a trend of presenting a lower LVEF (r=-0,262, p=0.082). Finally, we revealed a positive relationship between VAT and atrial fibrillation incidence (r=0,352, p=0.018). Conclusion Prolongation of VAT predicts the incidence of burn-out stage in patients with HCM and atrial fibrillation. Therefore, it seems to be a promising, inexpensive ECG marker for HCM progression and severity. Our findings emphasize the pivotal role of the ECG as a useful and inexpensive tool in the diagnostic follow-up of HCM.

Atrial rates during treated ventricular tachycardia in patients with implantable cardioverter defibrillators: clinical implications of a vagal sinus node response

Abstract Introduction Autonomic tone plays an important role in the genesis and sustenance of ventricular tachycardia (VT). Whilst sympathetic hyperactivity is an established driver of ventricular arrhythmias, sinus node response during VT varies broadly between patients, and can be paradoxical. Purpose We hypothesized that device-detected changes in sinus node rate could be an important surrogate of the autonomic response to VT, and may exert significant – and potentially modifiable – haemodynamic consequences independent of ventricular activity. Methods Device electrograms were analysed from consecutive patients with dual chamber implantable cardioverter defibrillators (ICDs) requiring anti-tachycardia pacing (ATP) or defibrillation for sustained monomorphic VT. Atrial rates were measured before VT onset (‘baseline’) and again at the point of detection by the device. Sinus node response was characterized as ‘stable’ (atrial rate remained within 10% of baseline), ‘sympathetic’ (atrial rate increased &amp;gt;10%) or ‘vagal’ (atrial rate decreased &amp;gt;10%). Patients who did not maintain ventriculoatrial dissociation or who presented in atrial tachyarrhythmia were excluded. Symptoms and electrical response to ICD therapies were recorded. Results 172 treated episodes of VT were included from 97 patients (median age: 69 years, 65% male, 31% ischaemic cardiomyopathy, median ventricular rate: 205bpm, median ejection fraction: 30%). Sinus node response was stable in 55%, sympathetic in 24% and vagal in 21%. A vagal response was associated with ATP-refractory VT (OR: 2.2 (1.1-4.8) p=0.03) and, when adjusting for ventricular rate, was independently associated with symptoms of presyncope or syncope (adjusted OR: 6 (2.7-13.7), p&amp;lt;0.0001). Conclusions This preliminary analysis suggests that a vagal sinus node response during VT is associated with adverse outcomes in ICD patients. Vagolytic therapy has recently been demonstrated to improve haemodynamic tolerance during VT ablation; whether supportive atrial pacing during VT could mitigate symptoms and potentiate arrhythmia termination in ICD patients warrants further exploration. Figure 1: Change in sinus node rate during sustained monomorphic ventricular tachycardia in patients with dual chamber ICDs, stratified by the occurrence of presyncopal symptoms or syncopeFigure 1

Local ventricular activation at the distal great cardiac vein determines right- and left-sided approach for catheter ablation of outflow tract arrhythmias: a simple and rapid discriminator

Abstract Background When the precordial transition zone (TZ) of idiopathic outflow tract arrhythmias (OTAs) is present around lead V3, it may be difficult to precisely determine which outflow tract is responsible for the origin of the OTAs from the ECG characteristics. Purpose We hypothesized that mapping around the distal portion of the great cardiac vein (dGCV) would be useful for identifying which outflow tract is the origin of OTAs during radiofrequency catheter ablation (RFA). Methods Among 28 OTA patients who underwent dGCV mapping and successful RFA at our institution from June 2021 to February 2024, 16 whose TZ during the OTAs was ＞lead V2 and ＜lead V4 were included in this study. In all patients, activation mapping around the dGCV with the novel 2.7 Fr over-the-wire (OTW)-type decapolar catheter was performed during the OTAs. Results In all patients, the mapping catheter could be easily placed in the dGCV. In patients whose OTAs were successfully ablated from the left-sided OT (n=7), the local ventricular activation time in the dGCV during OTAs preceded the QRS onset (LAT-dGCV) by -26.1±7.0 msec, which was significantly earlier than that of OTAs successfully ablated from the right-sided OT (n=9; -4.0±5.7 msec; p&amp;lt;0.001). An LAT-dGCV &amp;gt;-18 msec indicated a left-sided OTA, and right-sided and left-sided OTAs were completely distinct. Patients with an LAT-dGCV &amp;gt;-18 msec and mapping initiated first in the left-sided OT had shorter procedure times than those with mapping initiated first in the right-sided OT (p&amp;lt;0.001). Conclusions Mapping the dGCV with this OTW-type catheter is easy and safe. The earliness of the local ventricular activation in the dGCV during OTAs could easily and precisely differentiate between right-sided and left-sided OTAs, resulting in a successful ablation with a shorter procedure time.

A mcgyvering way to left bundle branch area pacing : using the treadmill test machine ECG system and modified V1 / V6 leads connected to the pacing system analyser for left bundle branch area pacing

Abstract Background Left bundle branch area pacing (LBBaP) is a novel pacing modality which provides physiological synchronisation of both the ventricles. However, its use and adoption requires the presence of a standardised electrophysiological (EP) system with 12 lead ECG to show left bundle branch area capture. Purpose The aim of the study was to assess the feasibility and outcomes of using the conventional treadmill test (TMT) machine 12 lead ECG system and modified V1 and V6 leads connected to the pacing system analyser (PSA) to demonstrate conduction system capture during left bundle branch area pacing (LBBaP). Methods LBBaP was attempted by a single operator in a mixed cohort of patients at peripheral hospitals lacking the standardised EP system. The presence of LBB area capture was tested with the aid of the 12 lead ECG system connected to the standard TMT machine (1). Conduction system capture was also assessed using modified V1 and V6 leads connected to the PSA for measurement of V6 left ventricular activation time (LVAT)(2) . The baseline clinical, procedural, pacing, electrocardiographic parameters, echocardiographic response (&amp;gt; 10% improvement in ejection fraction {EF}) and clinical response to LBBaP were assessed. Results LBBaP was attempted in 19 patients and was successful in 18 patients (94.7%). Patient characteristics include age 66.7 +/- 11.47 years, female 47.37%, male 52.63%, ischaemic cardiomyopathy 10.52% and non-ischaemic cardiomyopathy 5.26% .The mean baseline EF and QRS duration was 45%+/-14% and 130.18 +/-10.45 milliseconds(ms) respectively. LBBaP threshold was 0.59 +/-0.168 volts and R wave amplitude was 12+/-3.5 millimetres , which remained stable during the mean follow up of 15.9 +/-13.67 months. The mean fluoroscopic duration was 11.57 +/-2.58 minutes and procedural time was 108.78+/-29.20 minutes. LBBaP resulted in impressive narrowing of the QRS duration to 102.39 +/-10.55 ms (p&amp;lt;0.001) with LVAT of 68.94 +/-9.94 ms. LVEF improved in the patients with cardiomyopathy from 33.4 +/- 5.77 % to 48.2+/-12.37 % (p=0.028) .Clinical and echocardiographic response was noted in 87.5% of patients with cardiomyopathy. Conclusion The 12 lead ECG system with the standardised TMT machine in conjunction with the modified V1 and V6 leads connected to the PSA is a feasible alternative to the EP system to perform successful left bundle branch area pacing.ECG leads connected during LBBapClinical profile of patients

Accuracy of endocardial abnormal electrogram characterization using a 17-AHA-segmental late boundary and voltage-dependent sensitivity annotation for ventricular tachycardia ablation

Abstract Background Substrate-based catheter ablation of ventricular tachycardia (VT) has become the mainstay therapy for patients with scar-related VT. Correct identification and timing of abnormal near-field EGMs and discerning it from far-field EGMs, is key for procedural success. The novel CARTO™ Late Activation Mapping (LAM) module provides fast and accurate annotation of near-field EGMs including late abnormal ventricular activation. For the algorithm to succeed, a late boundary (LB) annotation line should be positioned immediately behind the normal near-field EGM, however, since the timing of normal local near-field activation varies greatly throughout the endocardium, there is currently no consensus for the optimal LB positioning. We hypothesized that 17-AHA segmental annotation of the endocardial LB followed by scar-dependent sensitivity settings, will improve the accuracy of the near-field EGM characterization. Purpose To evaluate the accuracy of endocardial abnormal EGM characterization using a 17-AHA-segmental late boundary and voltage-dependent sensitivity annotation as compared to conventional mid-QRS LB positioning. Methods Five high-resolution substrate voltage maps were obtained from 5 patients (80% male, 68±7 years old, 80% ischemic cardiomyopathy) that underwent a catheter-based ablation for scar-related VT. A personalized CT-derived anatomical reconstruction of the 17-segment AHA model was co-registered offline with the electroanatomic voltage map, using ADAS3D software. Per segment, individual LB timings were set at the highest sensitivity. A gold standard annotation map was created by two independent experts after manual scrutiny of individual EGMs. Next, the expert map was compared to automatic maps created from segmental LB and mid-QRS LB positions at normal, high, highest or mixed (normal/high or normal/highest) sensitivities, focusing on EGM voltage and activation accuracy. Results A mean of 2041±1028 points per map were analyzed. Correct correlation of EGM annotation was found on average in 91% (activation) and 81% (voltage) for all segmental LB positioned maps (segLB), and in 83% (activation) and 77% (voltage) for all mid-QRS LB positioned maps (mid-QRSLB). The highest correlation with expert map for both activation and voltage annotation was found in the mixed sensitivity normal/highest map with segmental LB positioning (activation 98%, voltage 88%). The correlation on activation was significantly superior in the segLB map when compared to the normal sensitivity maps (p=0.0008 for mid-QRSLB and p=0.02 for segLB). For correlation on voltage, the segLBmap with mixed sensitivity was significantly superior compared to three mid-QRSLB maps at normal (p=0.04), high and highest (p=0.01) sensitivity. Conclusion Individualized, 17-AHA-segmental late boundary and voltage-dependent sensitivity annotation provides a possible accurate and clinically-relevant framework for substrate assessment. Prospective validation is needed.

A novel formula to assess the QT interval in ventricular paced rhythm

Abstract Background QT interval measurement in the presence of right ventricular pacing (RVP) represents a clinical challenge due to altered ventricular activation resulting in a prolonged QT-interval. The aim of this study is to compare the QT interval in patients before and after ventricular pacing to develop a new formula for QT interval assessment in patients with RVP. Methods and results All patients presenting to our pacemaker clinic with single- or dual chamber device were included in this prospective observational study. Inclusion criteria were no permanent right ventricular stimulation, an intrinsic QRS interval of &amp;lt;120 ms, and ventricular rate &amp;gt;35 bpm and &amp;lt;150 bpm. Three 12-lead electrocardiograms were recorded for each patient: during intrinsic rhythm and 2 following an atrial paced and a ventricular paced QRS at the same rate. The intrinsic QRS and QT time/JT time (QTi/JTi) were measured during intrinsic and subsequent RVP. To obtain the formula, all measurements were performed on 100 patients (mean age 74 ± 11.3, male 33%) (RV apical lead 30% and non-apical lead 70%). Based on our measurements, a new formula QT (non-paced) = 139.23 + 0.55 xQT (paced) was derived. A population of 482 individuals (mean age 75.5±13.2 years (SD), 64% male) with permanent RV pacing were used as a validation group. The intrinsic QRS and QT time were measured during SR and subsequent RVP. To assess the relationship between the predicted QT with RVP and the measured QT without RVP, linear correlations analyses were performed. Our formula had a strong correlation with the irrespective QT without RVP (r=0.50) Conclusion We proposed a new simple formula to accurately estimate QT during RVP. This formula can be easily utilized in clinical practice. Figure 1: MAD characteristic value via plots stands for Median Absolute Difference (i.e. by how many ms the prediction is estimated on average). Figure 2: "Forest Plot" illustrates the correlation coefficients in the form of a forest plot. The dot r represents r and the bars the 95% confidence intervalsMAD characteristic value via plots standForest Plot" illustrates the correlation

Relationship Between Electrical Parameters and Cardiac Synchrony in Patients Underwent Left Bundle Branch Area Pacing.

The study aims to assess cardiac synchrony under different left bundle branch area pacing (LBBAP) and evaluate the relationship between different surface or intracardiac electrical parameters and mechanical synchrony. Eighty-two patients with successful LBBAP were recruited. The electrical synchrony, evaluated by paced QRS duration (pQRSD) and Stim-LVAT (stimulus to left ventricular activation time), and mechanical synchrony, evaluated by thestandard deviation of the time-to-peak contraction velocity in 12 left ventricular segments (Tsd-12-LV), were compared between groups in patients underwent LBBAP. To investigate the relationship between different electrical parameters with mechanical synchrony under LBBAP, patients were divided into subgroups according to left ventricular activation time (LVAT, < 60, 60-70, and > 70ms), presence of left bundle branch (LBB) potential (positive, negative), QRS axis (normal, left axis deviation [LAD]), and potential to ventricular interval (PVI, < 20 and > 20ms). Mechanical synchrony was compared among the subgroups respectively 3 days post LBBAP procedure. No statistically significant differences were documented in electrical synchrony, evaluated by pQRSD, and mechanical synchrony, evaluated by Tsd-12-LV among the subgroups divided by the stim-LVAT, LBB potential, PVI duration, or paced QRS axis in the LBBAP group. LBB potential, PVI, or normal paced QRS axis is not the prerequisite for successful LBBAP and optimal cardiac synchrony. Adopting a Stim-LVAT value of less than 75ms to attain ideal electrical and mechanical synchrony during theLBBAP procedure may be applicable. http://www.chictr.org.cn/index.aspx. gov identifier: ChiCTR1800021104.

His Bundle Pacing and Left Bundle Branch Pacing in Patients with Heart Failure.

His bundle pacing (HBP) and left bundle branch pacing (LBBP) are emerging therapies for patients with heart failure and conduction disorders, offering potential advantages over traditional pacing methods. These approaches aim to restore physiological conduction and improve cardiac function more effectively. This study aims to evaluate the efficacy and safety of HBP and LBBP in patients with heart failure and conduction disturbances, comparing these techniques to conventional pacing. A comprehensive review of recent studies and clinical trials was conducted, focusing on the performance of HBP and LBBP in improving cardiac function, reducing QRS duration, and enhancing overall patient outcomes. The analysis includes data on clinical efficacy, procedural safety, and long-term benefits associated with these pacing modalities. Both HBP and LBBP have demonstrated significant improvements in cardiac function and clinical outcomes compared to conventional pacing. HBP effectively restores physiological conduction with improved synchronization and a reduction in QRS duration. LBBP has shown enhanced left ventricular activation, leading to better overall cardiac performance. Both techniques have been associated with a lower incidence of complications and a higher success rate in achieving optimal pacing thresholds. HBP and LBBP offer promising alternatives to traditional pacing for patients with heart failure and conduction disorders. These advanced pacing strategies provide superior clinical outcomes and improved cardiac function with reduced risk of complications. Further research and clinical trials are needed to fully establish the long-term benefits and safety profiles of these techniques in diverse patient populations.

Transvenous extraction of conduction system and lumenless pacing leads.

Conduction system pacing (CSP), often accomplished with lumenless pacing leads, is increasingly employed to achieve physiologic ventricular activation. There are limited data on the extraction of these leads. The objective of this study was to describe the safety and efficacy of extraction of CSP pacing leads and compare outcomes with extraction of non-CSP lumenless leads. Patients undergoing CSP/non-CSP lumenless lead removal were included. Outcomes of interest included rates of complete procedural success, complications, and successful reimplantation. Overall, 23 patients were included (n = 14 with CSP and n = 9 with non-CSP lumenless leads implanted in the right atrium, right ventricle, or septum). The mean age was 52.7 ± 24.0 years, 30% were female, and the mean lead age was 4.5 ± 4.4 years. The complete procedural success rate was 100%. One serious complication occurred in the non-CSP group but was unrelated to the lead of interest. Manual traction alone was successful in 57% of CSP cases (mean lead age 2.4 ± 1.7 years) and in 11% of non-CSP cases (mean lead age 7.9 ± 5.3 years). Laser sheaths were used in 43% of CSP cases and 89% of non-CSP cases; rotational cutting tools were used in no CSP cases and in 33% of non-CSP cases. Reimplantation in the conduction system was attempted with a left bundle branch pacing lead and successful in 80% (n = 4/5). Extraction of CSP and non-CSP lumenless leads is feasible with a high success rate and a good safety profile. CSP reimplantation after extraction is also feasible with good electrical performance.

Electrophysiologic characteristics and clinical correlation of right ventricular activation during left bundle branch area pacing (RV-LBBAP study)

BackgroundLeft bundle branch area pacing (LBBAP) results in a right bundle branch (RBB) delay pattern because of preexcitation of the left bundle. The mechanism of right ventricular (RV) activation during LBBAP is largely unknown. ObjectiveThe aim of the study was to analyze the electrophysiologic characteristics of RV activation by mapping the RBB during LBBAP and its clinical correlation. MethodsConsecutive patients who underwent successful LBBAP were included. RBB block, RV paced rhythm, and suboptimal intracardiac electrograms were excluded. LBBAP was performed with continuous recording of His bundle (HB) and RBB electrograms. RV activation was classified into 3 types based on the intracardiac electrogram: type I, RBB mediated; type II, transseptal activation; and type III, fusion pattern. ResultsOverall, 86 patients (94% left bundle branch pacing [LBBP]; 6% left ventricular septal pacing) were included. The mean age was 59.6 ± 12.8 years. Nonselective to selective capture transition was noted in 85% (n = 73). In patients with baseline normal QRS (n = 47), during selective LBBP (S-LBBP; n = 39), the most common pattern was type I (n = 35 [87%]), whereas during nonselective LBBP (NS-LBBP; n = 44), type III pattern (n = 40 [91%]) was common. In patients with left bundle branch block (n = 39), type III pattern was common during both S-LBBP and NS-LBBP. Type I pattern was noted only in patients with retrograde HB activation during S-LBBP. Left ventricular septal pacing showed type II activation in both groups. Patients without retrograde HB activation had higher left ventricular end-diastolic diameter, lower left ventricular ejection fraction, and prolonged HV interval compared with those with retrograde HB activation. ConclusionPhysiologic RBB-mediated (type I) activation of the right ventricle was the most common pattern observed during S-LBBP in patients with intact retrograde HB activation. Type III pattern was the most common pattern observed during NS-LBBP with fusion of multiple wavefronts from anterograde RBB activation, septal myocardial, and transverse interbundle connections.

Influence of native thin filament type on the regulation of atrial and ventricular myosin motor activity

Ca2+-mediated activation of thin filaments is a crucial step in initiating striated muscle contraction. To gain mechanistic insight into this regulatory process, thin filament (TF) components and myosin motors from diverse species and tissue sources are often combined in minimal in vitro systems. The contribution of tissue-specific TF composition with native myosin motors in generating contraction speed remains unclear. To examine TF-mediated regulation, we established a procedure to purify native TFs (nTF) and myosin motors (M-II) from the same cardiac tissue samples as low as 10 mg and investigated their influence on gliding speeds and Ca2+ sensitivity. The rabbit atrial and ventricular nTFs and M-II were assessed in in vitro nTF motility experiments under varying Ca2+ concentrations. The speed-pCa relationship yielded a maximum TF speed of 2.58 μm/s for atrial (aM-II) and 1.51 μm/s for ventricular myosin (vM-II), both higher than the respective unregulated actin filament gliding speeds. The Ca2+ sensitivity was different for both protein sources. After swapping the nTFs, the ventricular TFs increased their gliding speed on atrial myosin, while the atrial nTFs reduced their gliding speed on ventricular myosin. Swapping of the nTFs decreased the calcium sensitivity for both vM-II and aM-II, indicating a strong influence of the thin filament source. These studies suggest that the nTF-myosin combination is critical to understanding the Ca2+ sensitivity of the shortening speed. Our approach is highly relevant to studying precious human cardiac samples, i.e., small myectomy samples, to address the alteration of contraction speed and Ca2+ sensitivity in cardiomyopathies.

Global R-wave peak time for diagnosis of left bundle branch capture

BackgroundQRS axis deviation and rS configuration in V6 affect the ability of V6 R-wave peak time (RWPT) criterion to discriminate capture type during left bundle branch area pacing (LBBAP). ObjectiveWe hypothesized that combining RWPTs from lateral leads: I, aVL, V5, and V6 may better reflect left ventricular activation time and that such a global RWPT may be insensitive to changes in QRS configuration. MethodsThe analysis included 519 electrocardiograms (ECGs) with nonselective left bundle branch pacing (nsLBBP) and 176 ECGs with left ventricular septal pacing (LVSP). Optimal RWPT cutoffs and area under the receiver operating curve (AUC) were determined for each lead and combinations of leads, to find the best RWPT criterion for discriminating nsLBBP from LVSP. Values were reported separately for healthy and diseased left conduction system groups. ResultsThe highest AUC of 97.1/89.2% was obtained for the global RWPT, which combined leads I and V6. The AUC for single-lead RWPT, was highest for lead I, followed by V6, V5, and aVL with AUC of 95.1/87.4%, 93.6/87.1%, 93.0/86.5%, and 84.8/74.6%, respectively. The global RWPT criterion was not affected by variations in QRS configuration, as V6 and I RWPTs often showed opposite responses to changes in axis. In contrast, all single-lead RWPT criteria were sensitive to axis deviation and QRS configuration. Diagnostically optimal RWPT cutoffs for global RWPT and lead I RWPT were 162.5/187.5 ms, and 81.5/90.5 ms, respectively. ConclusionThe global RWPT criterion allows a more accurate diagnosis of LBBAP capture type independent of QRS configuration and axis.

Association of same-day urinary phenol levels and cardiac electrical alterations: analysis of the Fernald Community Cohort

BackgroundExposure to phenols has been linked in animal models and human populations to cardiac function alterations and cardiovascular diseases, although their effects on cardiac electrical properties in humans remains to be established. This study aimed to identify changes in electrocardiographic (ECG) parameters associated with environmental phenol exposure in adults of a midwestern large cohort known as the Fernald Community Cohort (FCC).MethodsDuring the day of the first comprehensive medical examination, urine samples were obtained, and electrocardiograms were recorded. Cross-sectional linear regression analyses were performed.ResultsBisphenol A (BPA) and bisphenol F (BPF) were both associated with a longer PR interval, an indication of delayed atrial-to-ventricle conduction, in females (p < 0.05) but not males. BPA combined with BPF was associated with an increase QRS duration, an indication of delayed ventricular activation, in females (P < 0.05) but not males. Higher triclocarban (TCC) level was associated with longer QTc interval, an indication of delayed ventricular repolarization, in males (P < 0.01) but not females. Body mass index (BMI) was associated with a significant increase in PR and QTc intervals and ventricular rate in females and in ventricular rate in males. In females, the combined effect of being in the top tertile for both BPA urinary concentration and BMI was an estimate of a 10% increase in PR interval. No associations were found with the other phenols.ConclusionHigher exposure to some phenols was associated with alterations of cardiac electrical properties in a sex specific manner in the Fernald cohort. Our population-based findings correlate directly with clinically relevant parameters that are associated with known pathophysiologic cardiac conditions in humans.

Cardiac Involvement in LAMA2-Related Muscular Dystrophy and SELENON-Related Congenital Myopathy: A Case Series.

LAMA2-related muscular dystrophy (LAMA2-MD) and SELENON-related myopathy (SELENON-RM) are two rare neuromuscular diseases characterized by proximal and axial muscle weakness, scoliosis, spinal rigidity, low bone quality and respiratory impairment. Cardiac involvement has previously been described in retrospective studies and case reports, but large case series and prospective studies in unselected cohorts are lacking. The objective of this study is to conduct prevalence estimations, perform cardiac phenotyping, and provide recommendations for clinical care. In this case series including two time points, we conducted comprehensive assessments with electrocardiography (ECG) and transthoracic echocardiography (TTE). ECGs were systematically assessed for a large subset of variables. TTE included left and right ventricular ejection fraction (LVEF/RVEF) and left ventricular global longitudinal strain (GLS), the latter being a more early and sensitive marker of left ventricular dysfunction. 21 LAMA2-MD (M = 5; 20±14 years) and 10 SELENON-RM patients (M = 7; 18±12 years) were included. In most patients, QRS fragmentation and Q waves, markers of heterogeneous ventricular activation, were present both at baseline and at follow-up. GLS was abnormal (age specific in children, > -18% in adults) in 33% of LAMA2-MD and 43% of SELENON-RM patients at baseline. Reduced LVEF (<52% in males, <54% in females and <55% in pediatric population) was observed in three LAMA2-MD patients at baseline and in none of the SELENON-RM patients. GLS and LVEF did not change between baseline and follow-up. RVEF was normal in all patients. ECG abnormalities and abnormal GLS are prevalent in LAMA2-MD and SELENON-RM, yet abnormal LVEF was only seen in LAMA2-MD patients. One LAMA2-MD patient had a clinically relevant deterioration in LVEF during 1.5-year follow-up. We advise routine screening of all patients with LAMA2-MD or SELENON-RM with ECG and echocardiography at diagnosis, minimally every two years from second decade of life and if new cardiac signs arise.

Electrocardiographic Criteria for the Diagnosis of Acute Myocardial Infarction in Patients with Left Bundle Branch Block

During normal conduction system, the first segment depolarized is interventricular septum, normal ventricular depolarization begins with the septal fascicle of the left bundle branch followed by a simultaneous depolarization of the remaining ventricular walls from endocardium to pericardium via the right and left bundle branches. In left bundle branch block (LBBB) condition, the left ventricular activation is delayed, and the initial septal activation is from right to left, secondary ST segment and T wave abnormalities occur, and septal Q waves indicative of an MI are absent. About 0.5 percent of patients with acute myocardial infarction had left bundle-branch block Patients with left bundle branch block (LBBB) and suspected of acute myocardial infarction (MI) is challenge to the clinician. A diagnosis of MI with electrocardiogram (ECG) is especially difficult in the setting of LBBB because of the characteristic ECG changes caused by altered septal and left free wall ventricular depolarization. Here we review the pathophysiology of LBBB in MI, highlight evolving paradigms for the diagnosis of suspected MI in patients with LBBB.

Relationship of different left bundle branch pacing sites and clinical outcomes in patients with heart failure

BackgroundLeft bundle branch pacing (LBBP) is a novel physiological pacing modality. However, whether it delivers comparable efficacy with different capture sites in patients with heart failure remains unclear. ObjectiveThis study aimed to assess the association between different pacing sites and the response of LBBP. MethodsForty-three consecutive patients with heart failure, referred for successful LBBP implantation, were prospectively recruited in this study. Patients were assigned to 3 subgroups according to the paced QRS complex morphology (left bundle branch trunk pacing [LBTP], left posterior fascicular pacing, or left anterior fascicular pacing groups). Echocardiograms and electrocardiograms were recorded and analyzed at baseline and 6-month follow-up. ResultsThe response rate was 95.0%, 88.2%, and 83.3% in LBTP, left posterior fascicular pacing, and left anterior fascicular pacing groups, respectively. All subgroups were efficient in narrowing the QRS complex (QRS complex narrowing: 38.1 ± 10.8 ms, 36.4 ± 12.6 ms, and 40.8 ± 10.8 ms) and improving cardiac function (LVEF improvement： 25.7% ± 8.1%, 15.3% ± 8.1%, and 18.8% ± 4.4%). Compared with left fascicular pacing, LBTP resulted in longer peak left ventricular activation time (76.5 ± 10.2 ms vs 82.3 ± 6.5 ms; P = .037) and shorter duration from intrinsicoid deflection in V1 or V2 to QRS end (128.0 ± 6.0 ms vs 113.3 ± 5.2 ms; P＜.0001), along with better improvement in septal systolic longitudinal strain (P = .007) and lateral-septal myocardial loading inhomogeneity (P = .036). Linear regression analysis further revealed that left bundle branch capture sites were strongly associated with the improvement in peak strain dispersion (model R2 = 0.586; P = .042) and LVEF (model R2 = 0.425; P < .0001). ConclusionDifferent left bundle branch capture sites led to a subtle difference in mechanical synchrony, which may, in turn, affect LVEF improvement in patients with heart failure.