Caroline J.M. van Deursen

Left ventricular endocardial pacing improves resynchronization therapy in canine left bundle-branch hearts.

Background—We investigated the benefits of the more physiological activation achieved by left ventricular (LV) endocardial pacing (ENDO) as compared with conventional epicardial (EPI) LV pacing in cardiac resynchronization therapy. Methods and Results—In 8 anesthetized dogs with experimental left bundle-branch block, pacing leads were positioned in the right atrium, right ventricle, and at 8 paired (EPI and ENDO) LV sites. Systolic LV pump function was assessed as LVdP/dtmax and stroke work and diastolic function as LVdP/dtmin. Electrical activation and dispersion of repolarization were determined from 122 epicardial and endocardial electrodes and from analysis of the surface ECG. Overall, ENDO-biventricular (BiV) pacing more than doubled the degree of electrical resynchronization and increased the benefit on LVdP/dtmax and stroke work by 90% and 50%, respectively, as compared with EPI-BiV pacing. During single-site LV pacing, the range of AV intervals with a >10% increase in LV resynchronization (79±31 versus 32±24 ms, P<0.05) and LVdP/dtmax (92±29 versus 63±39 ms) was significantly longer for ENDO than for EPI pacing. EPI-BiV but not ENDO-BiV pacing created a significant (40±21 ms) transmural dispersion of repolarization. Conclusions—Data from this acute animal study indicate that the use of an endocardial LV pacing electrode may increase the efficacy of resynchronization therapy as compared with conventional epicardial resynchronization therapy.

LV Endocardial Pacing Improves Resynchronization Therapy in Canine LBBB Hearts

Background—We investigated the benefits of the more physiological activation achieved by left ventricular (LV) endocardial pacing (ENDO) as compared with conventional epicardial (EPI) LV pacing in cardiac resynchronization therapy. Methods and Results—In 8 anesthetized dogs with experimental left bundle-branch block, pacing leads were positioned in the right atrium, right ventricle, and at 8 paired (EPI and ENDO) LV sites. Systolic LV pump function was assessed as LVdP/dtmax and stroke work and diastolic function as LVdP/dtmin. Electrical activation and dispersion of repolarization were determined from 122 epicardial and endocardial electrodes and from analysis of the surface ECG. Overall, ENDO-biventricular (BiV) pacing more than doubled the degree of electrical resynchronization and increased the benefit on LVdP/dtmax and stroke work by 90% and 50%, respectively, as compared with EPI-BiV pacing. During single-site LV pacing, the range of AV intervals with a >10% increase in LV resynchronization (79±31 versus 32±24 ms, P<0.05) and LVdP/dtmax (92±29 versus 63±39 ms) was significantly longer for ENDO than for EPI pacing. EPI-BiV but not ENDO-BiV pacing created a significant (40±21 ms) transmural dispersion of repolarization. Conclusions—Data from this acute animal study indicate that the use of an endocardial LV pacing electrode may increase the efficacy of resynchronization therapy as compared with conventional epicardial resynchronization therapy.

Endocardial Left Ventricular Pacing Improves Cardiac Resynchronization Therapy in Chronic Asynchronous Infarction and Heart Failure Models

Background— Studies in canine hearts with acute left bundle branch block (LBBB) showed that endocardial left ventricular (LV) pacing improves the efficacy of cardiac resynchronization therapy (CRT) compared with conventional epicardial LV pacing. The present study explores the efficacy of endocardial CRT in more compromised hearts and the mechanisms of such beneficial effects. Methods and Results— Measurements were performed in 22 dogs, 9 with acute LBBB, 7 with chronic LBBB combined with infarction (embolization; LBBB plus myocardial infarction, and concentric remodeling), and 6 with chronic LBBB and heart failure (rapid pacing, LBBB+HF, and eccentric remodeling). A head-to-head comparison was performed of the effects of endocardial and epicardial LV pacing at 8 sites. LV activation times were measured using ≈100 endocardial and epicardial electrodes and noncontact mapping. Pump function was assessed from right ventricular and LV pressures. Endocardial CRT resulted in better electric resynchronization than epicardial CRT in all models, although the benefit was larger in concentrically remodeled LBBB plus myocardial infarction than in eccentrically remodeled LBBB+HF hearts (19% versus 10%). In LBBB and LBBB+HF animals, endocardial conduction was ≈50% faster than epicardial conduction; in all models, transmural impulse conduction was ≈25% faster when pacing from the endocardium than from the epicardium. Hemodynamic effects were congruent with electric effects. Conclusions— Endocardial CRT improves electric synchrony of activation and LV pump function compared with conventional epicardial CRT in compromised canine LBBB hearts. This benefit can be explained by a shorter path length along the endocardium and by faster circumferential and transmural impulse conduction during endocardial LV pacing.

Myocardial Infarction Does Not Preclude Electrical and Hemodynamic Benefits of Cardiac Resynchronization Therapy in Dyssynchronous Canine Hearts

Background—Several studies suggest that patients with ischemic cardiomyopathy benefit less from cardiac resynchronization therapy. In a novel animal model of dyssynchronous ischemic cardiomyopathy, we investigated the extent to which the presence of infarction influences the short-term efficacy of cardiac resynchronization therapy. Methods and Results—Experiments were performed in canine hearts with left bundle branch block (LBBB, n=19) and chronic myocardial infarction, created by embolization of the left anterior descending or left circumflex arteries followed by LBBB (LBBB+left anterior descending infarction [LADi; n=11] and LBBB+left circumflex infarction [LCXi; n=7], respectively). Pacing leads were positioned in the right atrium and right ventricle and at 8 sites on the left ventricular (LV) free wall. LV pump function was measured using the conductance catheter technique, and synchrony of electrical activation was measured using epicardial mapping and ECG. Average and maximal improvement in electric resynchronization and LV pump function by right ventricular+LV pacing was similar in the 3 groups; however, the site of optimal electrical and mechanical benefit was LV apical in LBBB hearts, LV midlateral in LBBB+LCXi hearts and LV basal-lateral in LBBB+LADi hearts. The best site of pacing was not the site of latest electrical activation but that providing the largest shortening of the QRS complex. During single-site LV pacing the range of atrioventricular delays yielding ≥70% of maximal hemodynamic effect was approximately 50% smaller in infarcted than noninfarcted LBBB hearts (P<0.05). Conclusions—Cardiac resynchronization therapy can improve resynchronization and LV pump function to a similar degree in infarcted and noninfarcted hearts. Optimal lead positioning and timing of LV stimulation, however, require more attention in the infarcted hearts.

Strategies to improve cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) emerged 2 decades ago as a useful form of device therapy for heart failure associated with abnormal ventricular conduction, indicated by a wide QRS complex. In this Review, we present insights into how to achieve the greatest benefits with this pacemaker therapy. Outcomes from CRT can be improved by appropriate patient selection, careful positioning of right and left ventricular pacing electrodes, and optimal timing of electrode stimulation. Left bundle branch block (LBBB), which can be detected on an electrocardiogram, is the predominant substrate for CRT, and patients with this conduction abnormality yield the most benefit. However, other features, such as QRS morphology, mechanical dyssynchrony, myocardial scarring, and the aetiology of heart failure, might also determine the benefit of CRT. No single left ventricular pacing site suits all patients, but a late-activated site, during either the intrinsic LBBB rhythm or right ventricular pacing, should be selected. Positioning the lead inside a scarred region substantially impairs outcomes. Optimization of stimulation intervals improves cardiac pump function in the short term, but CRT procedures must become easier and more reliable, perhaps with the use of electrocardiographic measures, to improve long-term outcomes.

Transseptal Conduction as an Important Determinant for Cardiac Resynchronization Therapy, as Revealed by Extensive Electrical Mapping in the Dyssynchronous Canine Heart

Background—Simple conceptual ideas about cardiac resynchronization therapy assume that biventricular (BiV) pacing results in collision of right and left ventricular (LV) pacing–derived wavefronts. However, this concept is contradicted by the minor reduction in QRS duration usually observed. We investigated the electric mechanisms of cardiac resynchronization therapy by performing detailed electric mapping during extensive pacing protocols in dyssynchronous canine hearts. Methods and Results—Studies were performed in anesthetized dogs with acute left bundle-branch block (LBBB, n=10) and chronic LBBB with tachypacing-induced heart failure (LBBB+HF, n=6). Activation times (AT) were measured using LV endocardial contact and noncontact mapping and epicardial contact mapping. BiV pacing reduced QRS duration by 21±10% in LBBB but only by 5±12% in LBBB+HF hearts. Transseptal impulse conduction was significantly slower in LBBB+HF than in LBBB hearts (67±9 versus 44±16 ms, respectively), and in both groups significantly slower than transmural LV conduction (≈30 ms). In both groups QRS duration and vector and the epicardial AT vector amplitude and angle were significantly different between LV and BiV pacing, whereas the endocardial AT vector was similar. During variation of atrioventricular delay while LV pacing, and ventriculo-ventricular delay while BiV pacing, the optimal hemodynamic effect was achieved when epicardial AT and QRS vectors were minimal and endocardial AT vector indicated LV preexcitation. Conclusions—Due to slow transseptal conduction, the LV electric activation sequence is similar in LV and BiV pacing, especially in failing hearts. Optimal hemodynamic cardiac resynchronization therapy response coincides with minimal epicardial asynchrony and QRS vector and LV preexcitation.

Vectorcardiographic QRS area as a novel predictor of response to cardiac resynchronization therapy

BACKGROUND QRS duration and left bundle branch block (LBBB) morphology are used to select patients for cardiac resynchronization therapy (CRT). We investigated whether the area of the QRS complex (QRSAREA) on the 3-dimensional vectorcardiogram (VCG) can improve patient selection. METHODS VCG (Frank orthogonal lead system) was recorded prior to CRT device implantation in 81 consecutive patients. VCG parameters, including QRSAREA, were assessed, and compared to QRS duration and morphology. Three LBBB definitions were used, differing in requirement of mid-QRS notching. Responders to CRT (CRT-R) were defined as patients with ≥15% reduction in left ventricular end systolic volume after 6months of CRT. RESULTS Fifty-seven patients (70%) were CRT-R. QRSAREA was larger in CRT-R than in CRT non-responders (140±42 vs 100±40 μVs, p<0.001) and predicted CRT response better than QRS duration (AUC 0.78 vs 0.62, p=0.030). With a 98μVs cutoff value, QRSAREA identified CRT-R with an odds ratio (OR) of 10.2 and a 95% confidence interval (CI) of 3.4 to 31.1. This OR was higher than that for QRS duration >156ms (OR=2.5; 95% CI 0.9 to 6.6), conventional LBBB classification (OR=5.5; 95% CI 0.9 to 32.4) or LBBB classification according to American guidelines (OR=4.5; 95% CI 1.6 to 12.6) or Strauss (OR=10.0; 95% CI 3.2 to 31.1). CONCLUSION QRSAREA is an objective electrophysiological predictor of CRT response that performs at least as good as the most refined definition of LBBB. CONDENSED ABSTRACT In 81 candidates for cardiac resynchronization therapy (CRT) we measured the area of the QRS complex (QRSAREA) using 3-dimensional vectorcardiography. QRSAREA was larger in echocardiographic responders than in non-responders and predicted CRT response better than QRS duration and than simple LBBB criteria. QRSAREA is a promising electrophysiological predictor of CRT response.

Vectorcardiography as a Tool for Easy Optimization of Cardiac Resynchronization Therapy in Canine Left Bundle Branch Block Hearts

Background—In cardiac resynchronization therapy (CRT), optimization of left ventricular (LV) stimulation timing is often time consuming. We hypothesized that the QRS vector in the vectorcardiogram (VCG) reflects electric interventricular dyssynchrony, and that the QRS vector amplitude (VAQRS), halfway between that during left bundle branch block (LBBB) and LV pacing, reflects optimal resynchronization, and can be used for easy optimization of CRT. Methods and Results—In 24 canine hearts with LBBB (12 acute, 6 with heart failure, and 6 with myocardial infarction), the LV was paced over a wide range of atrioventricular (AV) delays. Surface ECGs were recorded from the limb leads, and VAQRS was calculated in the frontal plane. Mechanical interventricular dyssynchrony (MIVD) was determined as the time delay between upslopes of LV and right ventricular pressure curves, and systolic function was assessed as LV dP/dtmax. VAQRS and MIVD were highly correlated (r=0.94). The VAQRS halfway between that during LV pacing with short AV delay and intrinsic LBBB activation accurately predicted the optimal AV delay for LV pacing (1 ms; 95% CI, –5 to 8ms). Increase in LV dP/dtmax at the VCG predicted AV delay was only slightly lower than the highest observed [INCREMENT]LV dP/dtmax (–2.7%; 95% CI, –3.6 to –1.8%). Inability to reach the halfway value of VAQRS during simultaneous biventricular pacing (53% of cases) was associated with suboptimal hemodynamic response, which could be corrected by sequential pacing. Conclusions—The VAQRS reflects electric interventricular dyssynchrony and accurately predicts optimal timing of LV stimulation in canine LBBB hearts. Therefore, VCG may be useful as a reliable and easy tool for individual optimization of CRT.

The value of the 12-lead ECG for evaluation and optimization of cardiac resynchronization therapy in daily clinical practice

Based on existing literature and some new data we propose a simple three-step strategy using the standard 12-lead ECG for patient selection and optimal delivery of cardiac resynchronization therapy (CRT). (1) Complete LBBB with regard to the indication for CRT can probably best be identified by a QRS duration of ≥ 130 ms for women and ≥ 120 ms for men with the presence of mid-QRS notch-/slurring in ≥ 2 contiguous leads of V1, V2, V5, V6, I and aVL. (2) Left ventricular (LV) free wall pacing should result in a positive QRS complex in lead V1, with estimation of the exact LV lead position in the circumferential and apico-basal direction using lead aVF and the precordial leads, respectively. Wide and fractionated LV-paced QRS complexes may indicate pacing in scar tissue. (3) Atrioventricular and interventricular stimulation intervals may be optimized by adjusting them until precordial leads show fusion patterns between left and right ventricular activation wavefronts in the QRS complex.

T-Wave Area Predicts Response to Cardiac Resynchronization Therapy in Patients with Left Bundle Branch Block

Chronic heart failure patients with a left ventricular (LV) conduction delay, mostly due to left bundle branch block (LBBB), generally derive benefit from cardiac resynchronization therapy (CRT). However, 30–50% of patients do not show a clear response to CRT. We investigated whether T‐wave analysis of the ECG can improve patient selection.