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

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

Comparison of septal strain patterns in dyssynchronous heart failure between speckle tracking echocardiography vendor systems

AIM: To analyze inter-vendor differences of speckle tracking echocardiography (STE) in imaging cardiac deformation in patients with dyssynchronous heart failure. METHODS AND RESULTS: Eleven patients (all with LBBB, median age 60.7 years, 9 males) with implanted cardiac resynchronization therapy devices were prospectively included. Ultrasound systems of two vendors (i.e. General Electric and Philips) were used to record images in the apical four chamber view. Regional longitudinal strain patterns were analyzed with vendor specific software in the basal, mid and apical septal segments. Systolic strain (SS), time to peak strain (TTP) and septal rebound stretch (SRS) were determined during four pacing settings, resulting in 44 unique strain patterns per segment (total 132 patterns). Cross correlation was used to analyze the comparability of the shape of 132 normalized strain patterns. Correlation of strain patterns of the two systems was high (R(2) median: 0.68, interquartile range: 0.53-0.82). Accordingly, strain patterns of intrinsic rhythm were recognized equally using both systems, when divided into three types. GE based SS (18.9 ± 4.7%) was significantly higher than SS determined by the Philips system (13.4 ± 4.3%). TTP was slightly but non-significantly lower in GE (384 ± 77 ms) compared to Philips (404 ± 83 ms) derived strain signals. Correlation of SRS between the systems was poor, due to minor differences in the strain signal and timing of aortic valve closure. CONCLUSIONS: The two systems provide similar shape of strain patterns. However, important differences are found in the amplitude, timing of systole and SRS. Until STE is standardized, clinical decision making should be restricted to pattern analysis

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

Synchronization of repolarization after cardiac resynchronization therapy: A combined clinical and modeling study

INTRODUCTION: The changes in ventricular repolarization after cardiac resynchronization therapy (CRT) are poorly understood. This knowledge gap is addressed using a multimodality approach including electrocardiographic and echocardiographic measurements in patients and using patient-specific computational modeling. METHODS: In 33 patients electrocardiographic and echocardiographic measurements were performed before and at various intervals after CRT, both during CRT-ON and temporary CRT-OFF. T-wave area was calculated from vectorcardiograms, and reconstructed from the 12-lead electrocardiography (ECG). Computer simulations were performed using a patient-specific eikonal model of cardiac activation with spatially varying action potential duration (APD) and repolarization rate, fit to a patient's ECG. RESULTS: During CRT-ON T-wave area diminished within a day and remained stable thereafter, whereas QT-interval did not change significantly. During CRT-OFF T-wave area doubled within 5 days of CRT, while QT-interval and peak-to-end T-wave interval hardly changed. Left ventricular (LV) ejection fraction only increased significantly increased after 1 month of CRT. Computer simulations indicated that the increase in T-wave area during CRT-OFF can be explained by changes in APD following chronic CRT that are opposite to the change in CRT-induced activation time. These APD changes were associated with a reduction in LV dispersion in repolarization during chronic CRT. CONCLUSION: T-wave area during CRT-OFF is a sensitive marker for adaptations in ventricular repolarization during chronic CRT that may include a reduction in LV dispersion of repolarization