Left Ventricular Lead Position
The traditional strategy for left ventricular lead placement was based on early haemodynamic studies indicating that the best acute response was achieved with lateral wall positions. Such strict anatomic criteria have not been validated in multicentre studies. Specifically, Post hoc analysis of the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) study showed no significant impact of lead position on outcomes including mortality and HF hospitalisations.34 Subsequently, apical lead position was shown to be associated with increased risk of HF death or hospitalisation in a Post hoc analysis of the MADIT-CRT, but this and other studies indicated significant heterogeneity in the ideal left ventricular pacing site to achieve optimal haemodynamic and clinical response.35–37 Furthermore, LV pacing on the site of transmural scar has been associated with an adverse haemodynamic response and scar burden has been associated with poor clinical response to CRT.38–41
Non-invasive methods, such as echocardiography, to identify the site of latest ventricular activation and avoid significant myocardial scar have become the focus of recent randomised trials. The Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy (TARGET) trial randomised 220 consecutive CRT patients to standard based LV lead placement or echocardiogram derived radial strain based LV lead placement. In the echocardiography group the LV lead was placed at the site of latest ventricular activation without evidence of significant myocardial scarring defined by decreased amplitude of contraction. There was a significant increase in the primary endpoint of positive left ventricular remodeling by echocardiogram as well as a decrease in a combined clinical endpoint of death and hospitalisation.42 Long-term follow-up of the TARGET study data at a mean of 39 months has suggested decreased mortality and improved LV remodeling.43 These results have been reinforced by the recently published Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) study.44 The Empiric Versus Imaging Guided Left Ventricular Lead Placement in Cardiac Resynchronization Therapy (ImagingCRT) trial should be complete in the near future and will further evaluate echocardiogram speckle tracking combined with cardiac and single photon emission computed tomography-computed tomography (SPECT CT) to guide lead implant site.45
In addition to late mechanical contraction to guide lead placement, there are accumulating data to show that electrical delay at the site of LV pacing is a strong predictor of CRT response. The most commonly used measure is the QLV interval, which is the time from the onset of the QRS complex to the peak of the local electrogram at the LV electrode. The QLV is a strong predictor of acute haemodynamic response, both with BiV and LV only pacing.46 In addition, QLV is a strong independent predictor of echocardiographic remodeling response as well as quality of life improvement with QLV.47 An analysis of the RV–LV interval, another measure of electrical delay, from the Pacing Evaluation-Atrial Support Study in Cardiac Resynchronization Therapy (PEGASUS CRT) trial showed that this was an independent measure of HF events.48
Device Optimisation
AV delay programming has been shown to have haemodynamic effects in left ventricular pacing but its use is controversial and routine optimisation is not recommended in the current guidelines based on recent trial results.1,49 Despite this fact, almost all trials studying CRT in HF used an echocardiographic method to attempt to improve AV synchrony.50
The method of left ventriculoventricular (VV) optimisation has also been controversial. VV optimisation was somewhat limited in the past as early devices allowed only simultaneous BiV pacing. Current devices are much more complex and diverse allowing individualised programming of the VV intervals and proprietary device algorithms are designed to optimise VV synchrony making programming more complex. Unfortunately, manual VV optimisation is time-consuming and requires an understanding of both interventricular (left ventricular relative to right ventricular contraction) and the intraventricular (septa-to-posterior delay of the LV) dyssnchrony.50 Methods to measure dyssnchrony have included time-consuming echocardiographic measures as well as left ventricular outflow tract (LVOT) velocity time integral (VTI) measurement at different device settings for optimisation.
More recent large clinical trials such as the SmartDelay determined AV Optimization: A Comparison of AV Optimization Methods Used in Cardiac Resynchronization Therapy (SMART-AV) trial and Frequent Optimization Study using the QuickOpt Method (Freedom) trial used device algorithms for AV and VV optimisation and did not show benefit in clinical endpoints resulting in the current guidelines recommending against routine AV or VV optimisation.1,51,52 The SMART-AV trial randomised CRT patients to a fixed AV delay, echocardiographic mitral inflow based AV delay, or an automated device algorithm based AV delay and found no difference in clinical outcomes or left ventricular end-systolic volume at six months.51 A substudy of the SMART-AV trial using the QLV interval at the LV pacing site showed that the SmartDelay method improved remodeling at six months among patients with long QLV intervals and the LV pacing site.53 The recently published ADAPTIVE trial randomised patients with a normal intrinsic AV interval to left ventricular fusing pacing verses echocardiography optimised BiV pacing and demonstrated non-inferiority in the left ventricular pacing cohort. Higher percent left ventricular pacing was associated with improved clinical outcomes.54 Using AV and VV optimisation in non-responders to CRT and in specific patient populations needs further review.