Cardiac resynchronization therapy: mechanisms of action and scope for further improvement in cardiac function
Siana Jones1, Joost Lumens2, S M Afzal Sohaib3
1Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.
Insights
Optimizing atrioventricular (AV) delay significantly improves cardiac function in patients receiving cardiac resynchronization therapy (CRT). Further gains are possible with enhanced ventricular resynchronization strategies.
Area of Science:
- Cardiology
- Biomedical Engineering
- Clinical Electrophysiology
Background:
- Cardiac resynchronization therapy (CRT) improves cardiac function through ventricular synchrony and atrioventricular (AV) timing.
- Clinical data derived from the BRAVO trial (NCT01258829).
Purpose of the Study:
- To determine the relative importance of AV timing and ventricular synchrony in CRT's haemodynamic benefits.
- To explore potential for further cardiac function improvement via enhanced ventricular resynchronization.
Main Methods:
- Utilized the CircAdapt haemodynamic model for simulations.
- Conducted haemodynamic measurements in 87 CRT patients, adjusting AV delay at varying heart rates.
- Assessed QRS duration, ventricular fusion, and haemodynamic response.
Main Results:
- Simulations indicated AV delay optimization accounts for significant haemodynamic improvement (e.g., 69% with specific parameters).
- Additional ventricular resynchronization yielded further blood pressure increases.
- In patients, ventricular fusion shortened QRS duration and improved systolic blood pressure; however, optimal haemodynamics were not always achieved with fusion.
Conclusions:
- Shortening AV delay to improve left ventricular (LV) preloading is a key mechanism for CRT-induced cardiac improvement.
- Significant potential exists for enhanced CRT outcomes through more efficient ventricular resynchronization methods.
Aims:
Cardiac 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 Results:
We 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.
Conclusions:
Improving 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 Registration:
Our 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.
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