Cardiac resynchronization therapy: mechanisms of action and scope for further improvement in cardiac function

Abstract

AimsCardiac resynchronization therapy (CRT) may exert its beneficial haemodynamic effect by improving ventricular synchrony and improving atrioventricular (AV) timing. The aim of this study was to establish the relative importance of the mechanisms through which CRT improves cardiac function and explore the potential for additional improvements with improved ventricular resynchronization.Methods and ResultsWe performed simulations using the CircAdapt haemodynamic model and performed haemodynamic measurements while adjusting AV delay, at low and high heart rates, in 87 patients with CRT devices. We assessed QRS duration, presence of fusion, and haemodynamic response. The simulations suggest that intrinsic PR interval and the magnitude of reduction in ventricular activation determine the relative importance of the mechanisms of benefit. For example, if PR interval is 201 ms and LV activation time is reduced by 25 ms (typical for current CRT methods), then AV delay optimization is responsible for 69% of overall improvement. Reducing LV activation time by an additional 25 ms produced an additional 2.6 mmHg increase in blood pressure (30% of effect size observed with current CRT). In the clinical population, ventricular fusion significantly shortened QRS duration (Δ-27 ± 23 ms, P < 0.001) and improved systolic blood pressure (mean 2.5 mmHg increase). Ventricular fusion was present in 69% of patients, yet in 40% of patients with fusion, shortening AV delay (to a delay where fusion was not present) produced the optimal haemodynamic response.ConclusionsImproving LV preloading by shortening AV delay is an important mechanism through which cardiac function is improved with CRT. There is substantial scope for further improvement if methods for delivering more efficient ventricular resynchronization can be developed.Clinical Trial RegistrationOur clinical data were obtained from a subpopulation of the British Randomised Controlled Trial of AV and VV Optimisation (BRAVO), which is a registered clinical trial with unique identifier: NCT01258829, https://clinicaltrials.gov

Rationale and design of the randomized multicentre His Optimized Pacing Evaluated for Heart Failure (HOPE‐HF) trial

“…PR prolongation impairs LV filling, 9 while reducing prolonged PR intervals improves LV filling. 10 In patients with left bundle branch block (LBBB), optimizing left ventricular filling by shortening AV delay using biventricular pacing acutely improves acute cardiac function, as reflected by changes in LV dP/dt max , stroke volume, coronary artery flow, and systolic blood pressure (SBP). [11][12][13] Furthermore, data from large randomized trials of biventricular pacing in patients with LBBB have found that patients with prolonged native PR intervals appear to gain greater benefit from biventricular pacing.…”

“…Shortening pathologically prolonged PR intervals has the potential to improve cardiac function. PR prolongation impairs LV filling, while reducing prolonged PR intervals improves LV filling . In patients with left bundle branch block (LBBB), optimizing left ventricular filling by shortening AV delay using biventricular pacing acutely improves acute cardiac function, as reflected by changes in LV dP/dt max , stroke volume, coronary artery flow, and systolic blood pressure (SBP) …”

The concept of triple wavefront fusion during biventricular pacing: Using the EGM to produce the best acute hemodynamic improvement in CRT

“…Furthermore, it has been suggested that optimized BiVp also involves intrinsic conduction contributing to ventricular depolarization next to both right ventricular and left ventricular pacing (resp. RVp and LVp) wavefronts, in other words triple wavefront fusion …”

“…However, no such EGM method is available using the concept of aiming at triple wavefront fusion. Studies showing triple wavefront fusion during optimal BiVp have used electroanatomic mapping and surface electrocardiogram (ECG) to assess the presence of BiVp with fusion (BiVp‐fusion, respectively, triple wavefront fusion) . Although these are sophisticated methods to assess the contribution of three wavefronts to resynchronization, an EGM‐based method is mandatory to provide an easy automatic assessment.…”

The Modulating Effects of Cardiac Resynchronization Therapy on Myocardial Metabolism in Heart Failure

“…Cardiac resynchronization therapy (CRT) is a nonpharmacological therapy by which simultaneous stimulation of both ventricles improves HF symptoms and ventricular function, and furthers overall survival . A recent study has documented that CRT normalizes myocardial metabolic alterations, suggesting a strong relation between cardiac contractility and the bioenergetic system .…”