A left bundle branch block activation sequence and ventricular pacing influence voltage amplitudes: an in vivo and in silico study.

AIMS: The aim of this study was to investigate the influence of the activation sequence on voltage amplitudes by evaluating regional voltage differences during a left bundle branch block (LBBB) activation sequence vs. a normal synchronous activation sequence and by evaluating pacing-induced voltage differences. METHODS AND RESULTS: Twenty-one patients and three computer models without scar were studied. Regional voltage amplitudes were evaluated in nine LBBB patients who underwent endocardial electro-anatomic mapping (EAM). Pacing-induced voltage differences were evaluated in 12 patients who underwent epicardial EAM during intrinsic rhythm and right ventricular (RV) pacing. Three computer models customized for LBBB patients were created. Changes in voltage amplitudes after an LBBB (intrinsic), a normal synchronous, an RV pacing, and a left ventricular pacing activation sequence were assessed in the computer models. Unipolar voltage amplitudes in patients were approximately 4.5 mV (4.4-4.7 mV, ∼33%) lower in the septum when compared with other segments. A normal synchronous activation sequence in the computer models normalized voltage amplitudes in the septum. Pacing-induced differences were larger in electrograms with higher voltage amplitudes during intrinsic rhythm and furthermore larger and more variable at the epicardium [mean absolute difference: 3.6-6.2 mV, 40-53% of intrinsic value; interquartile range (IQR) differences: 53-63% of intrinsic value] compared to the endocardium (mean absolute difference: 3.3-3.8 mV, 28-30% of intrinsic value; IQR differences: 37-40% of intrinsic value). CONCLUSION: In patients and computer models without scar, lower septal unipolar voltage amplitudes are exclusively associated with an LBBB activation sequence. Pacing substantially affects voltage amplitudes, particularly at the epicardium.

Tailoring device settings in cardiac resynchronization therapy using electrograms from pacing electrodes.

Aims: Left ventricular (LV) fusion pacing appears to be at least as beneficial as biventricular pacing in cardiac resynchronization therapy (CRT). Optimal LV fusion pacing critically requires adjusting the atrioventricular (AV)-delay to the delay between atrial pacing and intrinsic right ventricular (RV) activation (Ap-RV). We explored the use of electrogram (EGM)-based vectorloop (EGMV) derived from EGMs of implanted pacing leads to achieve optimal LV fusion pacing and to compare it with conventional approaches. Methods and results: During CRT-device implantation, 28 patients were prospectively studied. During atrial-LV pacing (Ap-LVp) at various AV-delays, LV dP/dtmax, 12-lead electrocardiogram (ECG), and unipolar EGMs were recorded. Electrocardiogram and electrogram were used to reconstruct a vectorcardiogram (VCG) and EGMV, respectively, from which the maximum QRS amplitude (QRSampl), was extracted. Ap-RV was determined: (i) conventionally as the longest AV-delay at which QRS morphology was visually unaltered during RV pacing at increasing AV-delays(Ap-RVvis; reference-method); (ii) 70% of delay between atrial pacing and RV sensing (Ap-RVaCRT); and (iii) the delay between atrial pacing and onset of QRS (Ap-QRSonset). In both the EGMV and VCG, the longest AV-delay showing an unaltered QRSampl as compared with Ap-LVp with a short AV-delay, corresponded to Ap-RVvis. In contrast, Ap-QRSonset and Ap-RVaCRT were larger. The Ap-LVp induced increase in LV dP/dtmax was larger at Ap-RVvis, Ap-RVEGMV, and Ap-RVVCG than at Ap-QRSonset (all P < 0.05) and Ap-RVaCRT (P = 0.02, P = 0.13, and P = 0.03, respectively). Conclusion: In this acute study, it is shown that the EGMV QRSampl can be used to determine optimal and individual CRT-device settings for LV fusion pacing, possibly improving long-term CRT response.

Evaluation of Left Ventricular Endocardial Cardiac Resynchronization Therapy in a Non-responder with Ventricular Arrhythmias.

Approximately one third of patients treated with cardiac resynchronization therapy do not derive any detectable benefit. In these patients, acute invasive hemodynamic evaluation can be used for therapy optimization. This report describes the use of systematic invasive hemodynamic measurements for clinical decision making in a patient who experienced severe ventricular arrhythmias and clinical deterioration following a biventricular upgrade.

Automated cardiac arrest detection using a photoplethysmography wristband: algorithm development and validation in patients with induced circulatory arrest in the DETECT-1 study.

BACKGROUND: Unwitnessed out-of-hospital cardiac arrest is associated with low survival chances because of the delayed activation of the emergency medical system in most cases. Automated cardiac arrest detection and alarming using biosensor technology would offer a potential solution to provide early help. We developed and validated an algorithm for automated circulatory arrest detection using wrist-derived photoplethysmography from patients with induced circulatory arrests. METHODS: In this prospective multicentre study in three university medical centres in the Netherlands, adult patients (aged 18 years or older) in whom short-lasting circulatory arrest was induced as part of routine practice (transcatheter aortic valve implantation, defibrillation testing, or ventricular tachycardia induction) were eligible for inclusion. Exclusion criteria were a known bilateral significant subclavian artery stenosis or medical issues interfering with the wearing of the wristband. After providing informed consent, patients were equipped with a photoplethysmography wristband during the procedure. Invasive arterial blood pressure and electrocardiography were continuously monitored as the reference standard. Development of the photoplethysmography algorithm was based on three consecutive training cohorts. For each cohort, patients were consecutively enrolled. When a total of 50 patients with at least one event of circulatory arrest were enrolled, that cohort was closed. Validation was performed on the fourth set of included patients. The primary outcome was sensitivity for the detection of circulatory arrest. FINDINGS: Of 306 patients enrolled between March 14, 2022, and April 21, 2023, 291 patients were included in the data analysis. In the development phase (n=205), the first training set yielded a sensitivity for circulatory arrest detection of 100% (95% CI 94-100) and four false positive alarms; the second training set yielded a sensitivity of 100% (94-100), with six false positive alarms; and the third training set yielded a sensitivity of 100% (94-100), with two false positive alarms. In the validation phase (n=86), the sensitivity for circulatory arrest detection was 98% (92-100) and 11 false positive circulatory arrest alarms. The positive predictive value was 90% (95% CI 82-94). INTERPRETATION: The automated detection of induced circulatory arrests using wrist-derived photoplethysmography is feasible with good sensitivity and low false positives. These promising findings warrant further development of this wearable technology to enable automated cardiac arrest detection and alarming in a home setting. FUNDING: Dutch Heart Foundation (Hartstichting).

Physiology and Practicality of Left Ventricular Septal Pacing.

Left ventricular septal pacing (LVSP) and left bundle branch pacing (LBBP) have been introduced to maintain or correct interventricular and intraventricular (dys)synchrony. LVSP is hypothesised to produce a fairly physiological sequence of activation, since in the left ventricle (LV) the working myocardium is activated first at the LV endocardium in the low septal and anterior free-wall regions. Animal studies as well as patient studies have demonstrated that LV function is maintained during LVSP at levels comparable to sinus rhythm with normal conduction. Left ventricular activation is more synchronous during LBBP than LVSP, but LBBP produces a higher level of intraventricular dyssynchrony compared to LVSP. While LVSP is fairly straightforward to perform, targeting the left bundle branch area may be more challenging. Long-term effects of LVSP and LBBP are yet to be determined. This review focuses on the physiology and practicality of LVSP and provides a guide for permanent LVSP implantation.

Regional Left Ventricular Electrical Activation and Peak Contraction Are Closely Related in Candidates for Cardiac Resynchronization Therapy.

OBJECTIVES: This study determined the relationship between the timing of left ventricular (LV) electrical activation and peak contraction at potential LV pacing locations in candidates for cardiac resynchronization therapy (CRT). BACKGROUND: Targeting the LV lead to the region of latest electrical activation or the segment of latest peak contraction has both been shown to improve CRT response. Whether these regions correspond within CRT patients is uncertain. METHODS: Twenty-eight consecutive CRT candidates underwent intraprocedural coronary venous electroanatomic mapping using EnSite NavX. Peak contraction time of the mapped LV regions was determined using longitudinal strain derived from speckle tracking echocardiography. Electrical activation and peak contraction times were correlated on a per patient basis, and the regions of latest electrical activation and latest peak contraction were compared. RESULTS: Successful measurements by both techniques allowed analysis in 23 of 28 patients. There was a strong positive correlation between electrical activation and peak contraction times within each patient (R2 = 0.85 ± 0.09). However, the magnitude of the electrical activation-peak contraction relationship varied greatly among patients (slope of regression line: 4.05 ± 3.23). The regions of latest electrical activation and latest peak contraction corresponded in 19 of 23 (83%) patients and were adjacent in 4 patients. CONCLUSIONS: There is a close relationship between the timing of LV electrical activation and peak contraction in CRT candidates. This finding suggests that a strategy of determining the latest activated LV region based on speckle tracking echocardiography corresponds to that based on intracardiac measurements of electrical activation.

A novel approach for left ventricular lead placement in cardiac resynchronization therapy: Intraprocedural integration of coronary venous electroanatomic mapping with delayed enhancement cardiac magnetic resonance imaging.

BACKGROUND: Placing the left ventricular (LV) lead at a site of late electrical activation remote from scar is desired to improve cardiac resynchronization therapy (CRT) response. OBJECTIVE: The purpose of this study was to integrate coronary venous electroanatomic mapping (EAM) with delayed enhancement cardiac magnetic resonance (DE-CMR) enabling LV lead guidance to the latest activated vein remote from scar. METHODS: Eighteen CRT candidates with focal scar on DE-CMR were prospectively included. DE-CMR images were semi-automatically analyzed. Coronary venous EAM was performed intraprocedurally and integrated with DE-CMR to guide LV lead placement in real time. Image integration accuracy and electrogram parameters were evaluated offline. RESULTS: Integration of EAM and DE-CMR was achieved using 8.9 ± 2.8 anatomic landmarks and with accuracy of 4.7 ± 1.1 mm (mean ± SD). Maximal electrical delay ranged between 72 and 197ms (57%-113% of QRS duration) and was heterogeneously located among individuals. In 12 patients, the latest activated vein was located outside scar, and placing the LV lead in the latest activated vein remote from scar was accomplished in 10 patients and prohibited in 2 patients. In the other 6 patients, the latest activated vein was located in scar, and targeting alternative veins was considered. Unipolar voltages were on average lower in scar compared to nonscar (6.71 ± 3.45 mV vs 8.18 ± 4.02 mV [median ± interquartile range), P <.001) but correlated weakly with DE-CMR scar extent (R -0.161, P <.001) and varied widely among individual patients. CONCLUSION: Integration of coronary venous EAM with DE-CMR can be used during CRT implantation to guide LV lead placement to the latest activated vein remote from scar, possibly improving CRT.

Evaluation of the use of unipolar voltage amplitudes for detection of myocardial scar assessed by cardiac magnetic resonance imaging in heart failure patients.

BACKGROUND: Validation of voltage-based scar delineation has been limited to small populations using mainly endocardial measurements. The aim of this study is to compare unipolar voltage amplitudes (UnipV) with scar on delayed enhancement cardiac magnetic resonance imaging (DE-CMR). METHODS: Heart failure patients who underwent DE-CMR and electro-anatomic mapping were included. Thirty-three endocardial mapped patients and 27 epicardial mapped patients were investigated. UnipV were computed peak-to-peak. Electrograms were matched with scar extent of the corresponding DE-CMR segment using a 16-segment/slice model. Non-scar was defined as 0% scar, while scar was defined as 1-100% scar extent. RESULTS: UnipVs were moderately lower in scar than in non-scar (endocardial 7.1 [4.6-10.6] vs. 10.3 [7.4-14.2] mV; epicardial 6.7 [3.6-10.5] vs. 7.8 [4.2-12.3] mV; both p<0.001). The correlation between UnipV and scar extent was moderate for endocardial (R = -0.33, p<0.001), and poor for epicardial measurements (R = -0.07, p<0.001). Endocardial UnipV predicted segments with >25%, >50% and >75% scar extent with AUCs of 0.72, 0.73 and 0.76, respectively, while epicardial UnipV were poor scar predictors, independent of scar burden (AUC = 0.47-0.56). UnipV in non-scar varied widely between patients (p<0.001) and were lower in scar compared to non-scar in only 9/22 (41%) endocardial mapped patients and 4/19 (21%) epicardial mapped patients with scar. CONCLUSION: UnipV are slightly lower in scar compared to non-scar. However, significant UnipV differences between and within patients and large overlap between non-scar and scar limits the reliability of accurate scar assessment, especially in epicardial measurements and in segments with less than 75% scar extent.

Why QRS Duration Should Be Replaced by Better Measures of Electrical Activation to Improve Patient Selection for Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) is a well-known treatment modality for patients with a reduced left ventricular ejection fraction accompanied by a ventricular conduction delay. However, a large proportion of patients does not benefit from this therapy. Better patient selection may importantly reduce the number of non-responders. Here, we review the strengths and weaknesses of the electrocardiogram (ECG) markers currently being used in guidelines for patient selection, e.g., QRS duration and morphology. We shed light on the current knowledge on the underlying electrical substrate and the mechanism of action of CRT. Finally, we discuss potentially better ECG-based biomarkers for CRT candidate selection, of which the vectorcardiogram may have high potential.

Feasibility and Acute Hemodynamic Effect of Left Ventricular Septal Pacing by Transvenous Approach Through the Interventricular Septum.

BACKGROUND: Left ventricular septal (LVS) pacing reduces ventricular dyssynchrony and improves cardiac function relative to right ventricular apex (RVA) pacing in animals. We aimed to establish permanent placement of an LVS pacing lead in patients using a transvenous approach through the interventricular septum. METHODS AND RESULTS: Ten patients with sinus node dysfunction scheduled for dual-chamber pacemaker implantation were prospectively enrolled. A custom pacing lead with extended helix was introduced via the left subclavian vein and, after positioning against the right ventricular septum (RVS) using a preshaped guiding catheter, driven through the interventricular septum to the LVS. The acute hemodynamic effect of RVA, RVS, and LVS pacing was evaluated by invasive LVdP/dtmax measurements. The lead was successfully delivered to the LVS in all patients. Procedure time and fluoroscopy time shortened with experience. QRS duration was shorter during LVS pacing (144 ± 20 ms) than during RVA (172 ± 33 ms; P = 0.02 versus LVS) and RVS pacing (165 ± 17 ms; P = 0.004 versus LVS). RVA and RVS pacing reduced LVdP/dtmax compared with baseline atrial pacing (-7.1 ± 4.1% and -6.9 ± 4.3%, respectively), whereas LVS pacing maintained LVdP/dtmax at baseline level (1.0 ± 4.3%; P = 0.001 versus RVA and RVS). R-wave amplitude and pacing threshold were 12.2 ± 6.7 mV and 0.5 ± 0.2 V at implant and remained stable during 6-month follow-up without lead-related complications. CONCLUSIONS: Permanent placement of an LVS pacing lead by transvenous approach through the interventricular septum is feasible in patients. LVS pacing preserves acute left ventricular pump function. This new pacing method could serve as an alternative and hemodynamically preferable approach for antibradycardia pacing.

Vectorcardiographic QRS area identifies delayed left ventricular lateral wall activation determined by electroanatomic mapping in candidates for cardiac resynchronization therapy.

BACKGROUND: Delayed left ventricular (LV) lateral wall (LVLW) activation is considered the electrical substrate underlying LV dysfunction amenable to cardiac resynchronization therapy (CRT). OBJECTIVE: The purpose of this study was to assess LVLW activation in CRT candidates using coronary venous electroanatomic mapping (EAM) and to investigate whether the QRS area (QRSAREA) on the vectorcardiogram (VCG) can identify delayed LVLW activation. METHODS: Fifty-one consecutive CRT candidates (29 left bundle branch block [LBBB], 15 intraventricular conduction delay [IVCD], 7 right bundle branch block [RBBB]) underwent intraprocedural coronary venous EAM using EnSite NavX. VCGs were constructed from preprocedural digital 12-lead ECGs using the Kors method. QRSAREA was assessed and compared to QRS duration and 5 different LBBB definitions. RESULTS: Delayed LVLW activation (activation time >75% of QRS duration) occurred in 38 of 51 patients (29/29 LBBB, 8/15 IVCD, 1/7 RBBB). QRSAREA was larger in patients with than in patients without delayed LVLW activation (108 ± 42 µVs vs 51 ± 27 µVs, P < .001), and identified delayed LVLW activation better than QRS duration (area under the curve 0.89 [95% confidence interval 0.79-0.99] vs 0.49 [95% confidence interval 0.33-0.65]). QRSAREA >69 µVs diagnosed delayed LVLW activation with a higher sum of sensitivity (87%) and specificity (92%) than any of the LBBB definitions. Of the different LBBB definitions, the European Society of Cardiology textbook definition performed best with sensitivity of 76% and specificity of 100%. CONCLUSION: Coronary venous EAM can be used during CRT implantation to determine the presence of delayed LVLW activation. QRSAREA is a noninvasive alternative for intracardiac measurements of electrical activation, which identifies delayed LVLW activation better than QRS duration and LBBB morphology.

Different regions of latest electrical activation during left bundle-branch block and right ventricular pacing in cardiac resynchronization therapy patients determined by coronary venous electro-anatomic mapping.

AIM: Current targeted left ventricular (LV) lead placement strategy is directed at the latest activated region during intrinsic activation. However, cardiac resynchronization therapy (CRT) is most commonly applied by simultaneous LV and right ventricular (RV) pacing without contribution from intrinsic conduction. Therefore, targeting the LV lead to the latest activated region during RV pacing might be more appropriate. We investigated the difference in LV electrical activation sequence between left bundle-branch block (LBBB) and RV apex (RVA) pacing using coronary venous electro-anatomic mapping (EAM). METHODS AND RESULTS: Twenty consecutive CRT candidates with LBBB underwent intra-procedural coronary venous EAM during intrinsic activation and RVA pacing using EnSite NavX. Left ventricular lead placement was aimed at the latest activated region during LBBB according to current recommendations. In all patients, LBBB was associated with a circumferential LV activation pattern, whereas RVA pacing resulted in activation from the apex of the heart to the base. In 10 of 20 patients, RVA pacing shifted the latest activated region relative to LBBB. In 18 of 20 patients, the LV lead was successfully positioned in the latest activated region during LBBB. For the whole study population, LV lead electrical delay, expressed as percentage of QRS duration, was significantly shorter during RVA pacing than during LBBB (72 ± 13 vs. 82 ± 5%, P = 0.035). CONCLUSION: Right ventricular apex pacing alters LV electrical activation pattern in CRT patients with LBBB, and shifts the latest activated region in a significant proportion of these patients. These findings warrant reconsideration of the current practice of LV lead targeting for CRT.