Non-invasive assessment of ventricular electrical heterogeneity to optimize left bundle branch area pacing.

BACKGROUND: Left bundle branch area pacing (LBBAP) is a novel therapeutic option for bradycardia and heart failure patients. ECG belt is a novel technology for assessment of ventricular electrical heterogeneity (VEH) using multi-electrode ECG. A metric of overall VEH based on standard deviation of activation times (SDAT) from all electrodes in the ECG belt has been previously shown to predict cardiac resynchronization therapy (CRT) response. The aim of the study is to evaluate non-invasive assessment of VEH using ECG belt to optimize LBBAP. METHODS: VEH from a 40-electrode ECG belt was characterized in 20 patients (male 15, EF 33 ± 13%, NYHA class 3.05 ± 0.6; CRT indication 18) during LBBAP (20) and LBBAP-Optimized CRT (LOT-CRT-7), anodal capture (16), NS-LBBP (18), S-LBBP (5), LVSP (9). In addition to SDAT, regional (LV/RV) VEH was assessed with average left ventricular activation times (LVAT), SDAT of left-sided (LV dispersion) and right-sided (RV dispersion) electrodes. Optimal LBBAP was determined based on maximal SDAT and QRS duration (d) change. RESULTS: All metrics were significantly reduced (p < 0.0001 for ECG belt metrics, p = 0.0027 for QRSd) during LBBAP and LOT-CRT compared to intrinsic. QRSd, SDAT, LVAT, and LV and RV dispersion during optimal LBBAP were significantly lower (133 ± 20/157 ± 24; 20.5 ± 7.5/38.6 ± 9; 44.4 ± 14.3/61.4 ± 21; 11.6 ± 11.6/29.5 ± 15; 21.1 ± 7.8/42.5 ± 9.3; p < 0.0001) compared to intrinsic rhythm. However, they were not significantly different among selective, non-selective, anodal, and LV septal captures. EF and NYHA class improved to 46 ± 11% and 1.9 ± 0.6 (p < 0.001). CONCLUSIONS: LBBAP significantly reduced overall and regional (RV/LV) VEH, irrespective of the mechanism of capture. Detailed assessment of electrical heterogeneity using ECG belt may add valuable insights on effects of LBBAP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04583709.

Prognostic Assessment of Early Repolarization/J Wave Electrocardiographic Pattern in Patients With Stable Ischemic Heart Disease.

Recent studies suggested that early repolarization (ER)/J wave at the electrocardiogram (ECG) is associated with increased risk of sudden death and ventricular arrhythmias in patients with acute myocardial infarction. In this study, we prospectively assessed whether ER/J wave has any long-term prognostic implications in patients with stable ischemic heart disease (IHD). We enrolled consecutive clinically stable patients with documented IHD, referred to undergo a routine ECG. ER (typical concave ST-segment elevation) and J wave were diagnosed according to prospectively defined criteria. The final population included 617 patients with documented IHD (455 men; age 68.1 ± 11 years). ER/J wave was found in 138 patients (22.4%), 13 of whom (2.1%) showed ER and 133 (21.6%) a J wave. At a follow-up of 8.1±2.9 years, 160 deaths occurred (25.9%), 60 (9.7%) attributed to cardiovascular causes. Total mortality was lower in patients with versus those without ER/J wave (18.8% vs 28.0%; hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.40 to 0.93, p = 0.02). The difference, however, was not significant after adjustment for confounding clinical variables (HR 0.78, 95% CI 0.51 to 1.19, p = 0.25). No significant difference was found in cardiovascular death between patients with (7.2%) and those without (10.4%) ER/J wave (adjusted HR 0.78, 95% CI 0.40 to 1.55, p = 0.48). Similar results were obtained for ER and J wave separately, and for ECG location of ER/J wave (inferior or lateral/precordial) and type of J wave (notched or slurred). The ER/J wave pattern at the ECG is not associated with increased risk of long-term mortality in clinically stable patients with a documented history of IHD.

Simultaneous Entrainment Response Assessment at Multiple Sites.

BACKGROUND: The entrainment response, defined as the difference between the postpacing interval and the tachycardia cycle length (TCL) recorded from a mapping catheter, allows to track down the components of the tachycardia loop. OBJECTIVES: The aim of this study was to evaluate if the postpacing interval measured simultaneously from multiple sites that are remote from the pacing site (PPIR) could be clinically useful in mapping re-entrant circuits. METHODS: Ninety-two episodes of entrainment response in 29 patients with different macro-re-entrant tachycardias were evaluated using a standardized entrainment protocol. The spatial distribution of different values of PPIR-TCL in a simulation and a computational model of an entrained re-entrant tachycardia was also analyzed. RESULTS: The PPIR exceeded TCL by more than 20 milliseconds only if both pacing and recording sites were outside the tachycardia circuit. The PPIR-TCL at in-circuit sites was always ≤20 milliseconds. Sites with negative PPIR-TCL values were found either outside or inside the tachycardia circuit. CONCLUSIONS: Assessment of entrainment response from catheters remote from the pacing site may enhance spatial mapping of the tachycardia circuit. The PPIR-TCL above 20 milliseconds has an excellent positive predictive value in identifying sites outside the tachycardia circuit.

Early assessment of ventricular synchronization and function after left bundle-branch-area pacing with right bundle-branch block.

AIM: To evaluate ventricular synchronization and function in patients with right bundle-branch block after left bundle-branch-area pacing (LBBAP) by echocardiography. METHODS: Forty patients who successfully received LBBAP were selected and divided into the right bundle-branch block group (RBBB group) and the non-RBBB group by pre-operation ECG. Echocardiography and follow-up were performed 1 month after operation. Interventricular synchronization was evaluated by tissue Doppler (TDI), tissue mitral annular displacement (TMAD), and interventricular mechanical delay. The tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RVFAC), tricuspid annulus sidewall systolic velocity (TV-s'), left ventricular global ventricular longitudinal strain (GLS), right ventricular free wall longitudinal strain (LS-RV), standard deviation of left ventricular 18 segments peak time difference (SDt-L) and standard deviation of right ventricular free wall 3 segments peak time difference (SDt-R) were applied to evaluate intraventricular synchronization and ventricular function. RESULTS: The difference of displacement peak time of the tricuspid and mitral valves, namely ΔPTTV-MV measured by TMAD, the difference of systolic time to peak of the tricuspid and mitral valves, namely ΔTsTV-MV measured by TDI, were statistically different between the two groups (P < 0.05). Compared with the non-RBBB group, there were no statistically significant differences in the GLS, RVFAC, LS-RV, TAPSE, TV-s', SDt-L, SDt-R (P > 0.05). CONCLUSION: Echocardiography technology including two-dimensional speckle tracking imaging (2D-STI), TDI, and TMAD can effectively analyze interventricular synchronization, intraventricular synchronization, and ventricular function. Although the movement of the right ventricular myocardium in the RBBB group was slightly later than that of the left ventricular myocardium after LBBAP, LBBAP could still be applied in RBBB patients with pacing indication.

Functional Assessment of Ventricular Tachycardia Circuits and Their Underlying Substrate Using Automated Conduction Velocity Mapping.

OBJECTIVES: This study sought to describe the utility of automated conduction velocity mapping (ACVM) in ventricular tachycardia (VT) ablation. BACKGROUND: Identification of areas of slowed conduction velocity (CV) is critical to our understanding of VT circuits and their underlying substrate. Recently, an ACVM called Coherent Mapping (Biosense Webster Inc) has been developed for atrial mapping. However, its utility in VT mapping has not been described. METHODS: Patients with paired high-density VT activation and substrate maps were included. ACVM was applied to paired VT activation and substrate maps to assess regional CV and activation patterns. A combination of ACVM, traditional local activation time maps, electrogram analysis, and off-line calculated CV using triangulation were used to characterize zones of slowed conduction during VT and in substrate mapping. RESULTS: Fifteen patients were included in the study. In all cases, ACVM identified slow CV within the putative VT isthmus, which colocalized to the VT isthmus identified with entrainment. The dimensions of the VT isthmus with local activation time mapping were 37.8 ± 13.7 mm long and 8.7 ± 4.2 mm wide. In comparison, ACVM produced an isthmus that was shorter (length: 25.1 ± 10.6 mm; mean difference: 12.8; 95% CI: 7.5-18.0; P < 0.01) and wider (width: 18.8 ± 8.1 mm; mean difference: 10.1; 95% CI: 6.1-14.2; P < 0.01). In VT, the CV using triangulation at the entrance (8.0 ± 3.6 cm/s) and midisthmus (8.1 ± 4.3 cm/s) was not significantly different (P = 0.92) but was significantly faster at the exit (16.2 ± 9.7 cm/s; P < 0.01). In the paired substrate analysis, traditional local activation time isochronal mapping identified 6.3 ± 2.0 deceleration zones. In contrast, ACVM identified a median of 0 deceleration zones (IQR: 0-1; P < 0.01). CONCLUSIONS: ACVM is a novel complementary tool that can be used to accurately resolve complex VT circuits and identify slow conduction zones in VT but has limited accuracy in identifying slowed conduction during substrate-based mapping.

Anatomical and histological assessment of left bundle branch area pacing in human heart with refractory heart failure.

As an emerging pacing technique, left bundle branch area pacing (LBBAP) has served as a physiological pacing modality that overcomes the limitations of His bundle pacing (HBP) or right ventricular pacing. Three patients with terminal heart failure who were waiting for heart transplantation and met the indications of pacemaker implantations received LBBAP. Symptoms were relieved and stabilized and eventually received heart transplantation. Diseased hearts from the recipients were dissected post-transplantation, and the direct visual of pacing lead locations in the interventricular septum were evaluated, and the histopathological examination around the lead was conducted for the first time in human. As a result, we found that the locations of LBBAP leads were matched with fluoroscopic views during the procedure and Masson's staining showed extensive fibrosis occur around the lead but did not result in high thresholds.

Extended early meets late for assessment of conduction block along an ablation line.

PURPOSE: The purpose of the study was to investigate the usefulness of the extended early meets late (EEML) feature of the HD Coloring software for confirmation of bidirectional block along an ablation line. METHODS: A single-center prospective observational study of consecutive patients with atypical atrial flutter or persistent atrial fibrillation submitted to catheter ablation including linear lesions from January 2019 to June 2020, with confirmation of bidirectional block across ablation lines assessed with the feature EEML and a multipolar catheter was conducted. Patients were divided into two groups - those with versus those without bidirectional block - and different EEML thresholds were analyzed to assess which one had the better sensitivity and specificity to predict block. RESULTS: During the 24-month enrollment period, a total of 94 patients were included (50% males, mean age of 64 ± 10 years, 60% with structural heart disease) - 55 patients with versus 39 patients without confirmed a bidirectional block. Activation maps were performed during atrial pacing, with a median number of 1340 (interquartile range 1135-2060) points acquired in 11 ± 3 min, and a mean mapped cycle length of 287 ± 51 ms. The EEML feature was highly useful in detecting bidirectional block along ablation lines, with a 25% threshold value showing the highest discriminative performance (area under the curve of 0.93), 95% sensitivity and 92% specificity in predicting block. CONCLUSIONS: The EEML feature of the HD Coloring software is a useful addition to the CARTO mapping system for assessment of block across an ablation line. The threshold value of 25% is the most accurate.

A governing equation for rotor and wavelet number in human clinical ventricular fibrillation: Implications for sudden cardiac death.

BACKGROUND: Ventricular fibrillation (VF) is characterized by multiple wavelets and rotors. No equation to predict the number of rotors and wavelets observed during fibrillation has been validated in human VF. OBJECTIVE: The purpose of this study was to test the hypothesis that a single equation derived from a Markov M/M/∞ birth-death process could predict the number of rotors and wavelets occurring in human clinical VF. METHODS: Epicardial induced VF (256-electrode) recordings obtained from patients undergoing cardiac surgery were studied (12 patients; 62 epochs). Rate constants for phase singularity (PS) (which occur at the pivot points of rotors) and wavefront (WF) formation and destruction were derived by fitting distributions to PS and WF interformation and lifetimes. These rate constants were combined in an M/M/∞ governing equation to predict the number of PS and WF in VF episodes. Observed distributions were compared to those predicted by the M/M/∞ equation. RESULTS: The M/M/∞ equation accurately predicted average PS and WF number and population distribution, demonstrated in all epochs. Self-terminating episodes of VF were distinguished from VF episodes requiring termination by a trend toward slower PS destruction, slower rates of PS formation, and a slower mixing rate of the VF process, indicated by larger values of the second largest eigenvalue modulus of the M/M/∞ birth-death matrix. The longest-lasting PS (associated with rotors) had shorter interactivation time intervals compared to shorter-lasting PS lasting <150 ms (∼1 PS rotation in human VF). CONCLUSION: The M/M/∞ equation explains the number of wavelets and rotors observed, supporting a paradigm of VF based on statistical fibrillatory dynamics.

The assessment of Tp-e interval and Tp-e/QT ratio in patients with hyperthyroidism before and after thyroid surgery.

BACKGROUND: Ventricular repolarisation is assessed using the Tp-e interval and QT interval corrected by the heart rate (QTc) via an electrocardiogram (ECG). Prolonged Tp-e/QTc is related with an increased risk of arrhythmias and cardiac mortality. OBJECTIVE: This study was conducted at a single centre in collaboration with general surgery and cardiology clinics. We aimed to appraise the assessment of Tp-e interval and Tp-e/QT ratio in patients with hyperthyroidism before and after thyroid surgery. METHODS: Totally 65 patients with hyperthyroidism before and after thyroid surgery were enrolled in our study. In presurgical hospitalisation and six months after the thyroid surgery, we measured the electrocardiographic parameters again on same patients. All subjects who were investigated in this study were in sinus rhythm. Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were measured from the 12-lead electrocardiogram. RESULTS: Heart rate (P = .073), QT interval (P = .432) and QTc interval (P = .179) were similar before and after thyroid surgery. Tp-e interval (84.6 ± 13.1 vs 77.2 ± 10.9; P = .031), Tp-e/QT ratio (0.23 ± 0.04 vs 0.21 ± 0.04; P < .001), Tp-e/QTc ratio (0.21 ± 0.04 vs 0.19 ± 0.03; P < .001) and QTc dispersion (52.4 ± 7.2 vs 48.4 ± 7.4; P < .001) were significantly different before and after thyroid surgery. In correlation analysis, there was a significant correlation between preprocedural Tp-e/QTc ratio and preprocedural fT4 in patients with hyperthyroidism (r = 0.275, P = .026). CONCLUSION: Our study demonstrated that Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were shortened in patients with hyperthyroidism after thyroid surgery than before procedure. This study is considerable to display that hyperthyroidism may have a negative effect on cardiac conduction system, which potentially may induce formation of ventricular arrhythmias.

Epidemiology, evaluation, and management of conduction disturbances after transcatheter aortic valve replacement.

Aortic stenosis is the most common valvulopathy requiring replacement by means of the surgical or transcatheter approach. Transcatheter aortic valve replacement (TAVR) has quickly become a viable and often preferred treatment strategy compared to surgical aortic valve replacement. However, transcatheter heart valve system deployment not infrequently injures the specialized electrical system of the heart, leading to new conduction disorders including high-grade atrioventricular block and complete heart block (CHB) necessitating permanent pacemaker implantation (PPI), which may lead to deleterious effects on cardiac function and patient outcomes. Additional conduction disturbances (e.g., new-onset persistent left bundle branch block, PR/QRS prolongation, and transient CHB) currently lack clearly defined management algorithms leading to variable strategies among institutions. This article outlines the current understanding of the pathophysiology, patient and procedural risk factors, means for further risk stratification and monitoring of patients without a clear indication for PPI, our institutional approach, and future directions in the management and evaluation of post-TAVR conduction disturbances.

Temporal Incidence and Predictors of High-Grade Atrioventricular Block After Transcatheter Aortic Valve Replacement.

Background The temporal incidence of high-grade atrioventricular block (HAVB) after transcatheter aortic valve replacement (TAVR) is uncertain. As a result, periprocedural monitoring and pacing strategies remain controversial. This study aimed to describe the temporal incidence of initial episode of HAVB stratified by pre- and post-TAVR conduction and identify predictors of delayed events. Methods and Results Consecutive patients undergoing TAVR at a single center between February 2012 and June 2019 were retrospectively assessed for HAVB within 30 days. Patients with prior aortic valve replacement, permanent pacemaker (PPM), or conversion to surgical replacement were excluded. Multivariable logistic regression was performed to assess predictors of delayed HAVB (initial event >24 hours post-TAVR). A total of 953 patients were included in this study. HAVB occurred in 153 (16.1%). After exclusion of those with prophylactic PPM placed post-TAVR, the incidence of delayed HAVB was 33/882 (3.7%). Variables independently associated with delayed HAVB included baseline first-degree atrioventricular block or right bundle-branch block, self-expanding valve, and new left bundle-branch block. Forty patients had intraprocedural transient HAVB, including 16 who developed HAVB recurrence and 6 who had PPM implantation without recurrence. PPM was placed for HAVB in 130 (13.6%) (self-expanding valve, 23.7% versus balloon-expandable valve, 11.9%; P<0.001). Eight (0.8%) patients died by 30 days, including 1 unexplained without PPM present. Conclusions Delayed HAVB occurs with higher frequency in patients with baseline first-degree atrioventricular block or right bundle-branch block, new left bundle-branch block, and self-expanding valve. These findings provide insight into optimal monitoring and pacing strategies based on periprocedural ECG findings.

Direct in vivo assessment of global and regional mechanoelectric feedback in the intact human heart.

BACKGROUND: Inhomogeneity of ventricular contraction is associated with sudden cardiac death, but the underlying mechanisms are unclear. Alterations in cardiac contraction impact electrophysiological parameters through mechanoelectric feedback. This has been shown to promote arrhythmias in experimental studies, but its effect in the in vivo human heart is unclear. OBJECTIVE: The purpose of this study was to quantify the impact of regional myocardial deformation provoked by a sudden increase in ventricular loading (aortic occlusion) on human cardiac electrophysiology. METHODS: In 10 patients undergoing open heart cardiac surgery, left ventricular (LV) afterload was modified by transient aortic occlusion. Simultaneous assessment of whole-heart electrophysiology and LV deformation was performed using an epicardial sock (240 electrodes) and speckle-tracking transesophageal echocardiography. Parameters were matched to 6 American Heart Association LV model segments. The association between changes in regional myocardial segment length and activation-recovery interval (ARI; a conventional surrogate for action potential duration) was studied using mixed-effect models. RESULTS: Increased ventricular loading reduced longitudinal shortening (P = .01) and shortened ARI (P = .02), but changes were heterogeneous between cardiac segments. Increased regional longitudinal shortening was associated with ARI shortening (effect size 0.20 [0.01-0.38] ms/%; P = .04) and increased local ARI dispersion (effect size -0.13 [-0.23 to -0.03] ms/%; P = .04). At the whole organ level, increased mechanical dispersion translated into increased dispersion of repolarization (correlation coefficient r = 0.81; P = .01). CONCLUSION: Mechanoelectric feedback can establish a potentially proarrhythmic substrate in the human heart and should be considered to advance our understanding and prevention of cardiac arrhythmias.

A new implantable tool for repeated assessment of supraventricular electrophysiology and atrial fibrillation susceptibility in freely moving rats.

The complex pathophysiology of atrial fibrillation (AF) is governed by multiple risk factors in ways that are still elusive. Basic electrophysiological properties, including atrial effective refractory period (AERP) and conduction velocity, are major factors determining the susceptibility of the atrial myocardium to AF. Although there is a great need for affordable animal models in this field of research, in vivo rodent studies are limited by technical challenges. Recently, we introduced an implantable system for long-term assessment of AF susceptibility in ambulatory rats. However, technical considerations did not allow us to perform concomitant supraventricular electrophysiology measurements. Here, we designed a novel quadripolar electrode specifically adapted for comprehensive atrial studies in ambulatory rats. Electrodes were fabricated from medical-grade silicone, four platinum-iridium poles, and stainless-steel fixating pins. Initial quality validation was performed ex vivo, followed by implantation in adult rats and repeated electrophysiological studies 1, 4, and 8 wk postimplantation. Capture threshold was stable. Baseline AERP values (38.1 ± 2.3 and 39.5 ± 2.0 using 70-ms and 120-ms S1-S1 cycle lengths, respectively) confirmed the expected absence of rate adaptation in the unanesthetized state and validated our prediction that markedly higher values reported under anesthesia are nonphysiological. Evaluation of AF substrate in parallel with electrophysiological parameters validated our recent finding of a gradual increase in AF susceptibility over time and demonstrated that this phenomenon is associated with an electrical remodeling process characterized by AERP shortening. Our findings indicate that the miniature quadripolar electrode is a potent new tool, which opens a window of opportunities for better utilization of rats in AF research.NEW & NOTEWORTHY Rodents are increasingly used in AF research. However, technical challenges restrict long-term supraventricular electrophysiology studies in these species. Here, we developed an implantable electrode adapted for such studies in the rat. Our findings indicate that this new tool is effective for long-term follow-up of critical parameters such as atrial refractoriness. Obtained data shed light on the normal electrophysiology and on the increased AF susceptibility that develops in rats with implanted atrial electrodes over time.

Intraprocedural dynamics of cardiac conduction during transcatheter aortic valve implantation: Assessment by simultaneous electrophysiological testing.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with severe aortic stenosis and high to intermediate surgical risk. However, the proximity of the conduction system to the prosthesis landing zone bears the risk of atrioventricular conduction disorders. The underlying pathophysiology is not fully understood. OBJECTIVE: The purpose of this study was to characterize the impact of TAVI on the conduction system as assessed by simultaneous electrophysiological testing. METHODS: AH and HV intervals and QRS duration were measured using a quadripolar His catheter and surface electrocardiogram in 108 patients at baseline (BL), after balloon predilation (timepoint 1 [T1]), after implantation of the valve prosthesis (T2), and after postdilation, if deemed necessary (T3). RESULTS: Between BL and T2, significant increases of HV interval and QRS duration were observed, with a mean delta of +12.4 ms and +32.7 ms, respectively. Both balloon predilation and valve implantation had an impact on infranodal conduction. No significant increase of AH intervals was documented. The increase of QRS duration led to left bundle branch block (LBBB) in 57 patients (52.8%). Implantation depth positively correlated with QRS prolongation (ρ = 0.21, P = .042) but not with changes of AH or HV interval (ρ = -0.03, P = .762; and ρ = 0.15, P = .130, respectively). CONCLUSION: Electrophysiological testing during TAVI shows impairment of infranodal atrioventricular conduction by balloon predilation and valve implantation. This impairment is positively correlated with valve implantation depth and results in an increase of QRS duration with mainly LBBB pattern on surface electrocardiogram.

Female Athlete's Heart: Sex Effects on Electrical and Structural Remodeling.

BACKGROUND: Most of our knowledge on training-induced cardiac remodeling is derived from men, with the paucity of data from women representing an important gap in knowledge. The aim of the study was to define the electrocardiographic and morphological features of female athlete's heart, with special attention to differences related to sex and sport. METHODS: Seven hundred twenty Olympic athletes (360 females and 360 age- and sport-matched males, mean age: 23±5 years) were evaluated by clinical, resting, and exercise electrocardiography and echocardiography. RESULTS: Anterior T-wave inversion was more common in females than males (P<0.05). Left ventricular (LV) wall thickness and LV mass were greater in men (P<0.001). Females had smaller absolute but greater indexed LV and right ventricular (RV) dimensions as compared to males. Most women had normal LV geometry (80.8%). A progressive increase in LV/RV dimensions was observed in women from those engaged in skill, power, to mixed and endurance disciplines, with the endurance ones demonstrating the greatest degree of RV dilatation. Women had a peculiar biventricular adaptation, with higher LV/RV (1.41±0.16 versus 1.36±0.15, P<0.0001) and lower RV inflow/outflow ratio (P<0.001), as compared to men. CONCLUSIONS: Sex significantly affects cardiac remodeling in athletes, with females presenting a different electrical and structural remodeling. Women maintain a normal LV geometry, with relative larger increase of cavity dimensions compared with men. Type of sport has a relevant impact, with endurance athletes exhibiting the greatest degree of RV and LV dimensional remodeling. The present study confirms the need for a sex-based approach for interpreting the complex features of athlete's heart in women.