Where to Pace in the Right Ventricle?

Author: Dr Christopher Critoph
Specialist Registrar, Heart Failure and Devices, the Heart Hospital, London

Right ventricular pacing is standard therapy for the treatment of high-grade atrio-ventricular block and sick sinus syndrome. For decades the standard site for right ventricular (RV) passive lead placement was in the apex, which is straightforward to implant and has good stability. However, several studies have observed deleterious effects on left ventricular (LV) function with RV apical pacing. The advent of active screw-in leads has allowed physicians to pace from different sites in the RV, including the right ventricular outflow tract (RVOT), septum, and His bundle. The goal is a narrower QRS, reflecting more physiological, synchronous ventricular activation. Most implanters have their preferred technique, but what is the evidence to support the choice of site, and is it strong enough that the long-standing paradigm be changed?   

Ejection fraction
Pre-implant LV systolic function may be an important determinant of outcome with chronic RV pacing. In a study of 91 patients undergoing AV node ablation, with normal ejection fraction (EF), QRS duration and no other structural heart disease, nearly one third of patients were found to have a decline in EF of ≥5% with RV apical pacing (1). However, studies reporting echocardiographic and other haemodynamic changes often do not assess the clinical impact of their findings. It should also be noted that often the absolute effect size is small (a few percentage points), particularly given the large inter and intra-observer variability when calculating ejection fraction using echocardiography.

Duration of follow up is a potentially important consideration for trial design, as the deleterious effects of RV pacing may take years to develop. Multiple randomised controlled trials (RCT) have demonstrated these differences in EF become more pronounced with longer follow up.   However, this tends to vary with baseline LV function. In patients with mild to moderate baseline LV systolic function, pooled studies showed a higher overall LV EF (7.53%, 95% CI 2.79 - 12.27) in patients with non-RV apical pacing when followed for ≥ 1year (2). Notably, if baseline systolic function was preserved no such difference was elicited. A recent retrospective cohort study has suggested that LV dyssynchrony induced by RV apical pacing is associated with higher long term (up to 5 years) mortality and excess hospitalisations for heart failure (3). The patients with more dyssynchronous ventricles were more likely to be older, have coronary disease and poorer pre-implant LV systolic function. 

Procedural considerations
No significant difference between operating and fluoroscopy time has been shown between apical and non-apical positions, although there is a trend towards shorter times in the latter (4). Use of the postero-anterior, left and right anterior oblique fluoroscopic views are essential in determining lead position, as is a good understanding of RV anatomy (figure 1). Indeed many early studies of non-RV apical pacing sites may be flawed due to inaccuracies of lead position reporting (5). An anecdotal concern exists regarding a higher rate of lead displacement in non-apical RV pacing, although this is not supported by long-term outcome studies. As expected, the paced QRS duration is longer in RV apical pacing (2, 6). A recent meta-analysis identified implantation capture threshold and R wave amplitude (although statistically non-significant) to be favourable for leads in the apical compared to septal position, with similar impedance values (6). However at follow up there were no differences in threshold or sensing, although lead impedances were superior in non-apical leads. Some of these observations may be explained by the fact that active leads are often steroid eluting, and local myocardial inflammation and oedema settle over time. Studies are likely therefore to measure variables at different points in the natural history of-leads, and it seems there is little if any long-term difference in pacing parameters.

Non-RV apical pacing sites – which to choose?
His bundle specific pacing is generally regarded as more complex, time consuming, and unlikely to be reliably achieved by implanters not trained in electro-physiology. Some clinical results with limited success have been published, although a higher complication rate and stimulation threshold remain concerns.

Delivery of a pacing lead to the trabeculated part of the RVOT septum can be achieved relatively easily, and techniques using RVOT specific 3D stylet shapes exist (7). Pacing and sensing parameters at this site are indistinguishable from the apex (8). Anecdotally there have been concerns that implanting here results in increased ectopy although this is not supported in the literature. One possible advantage of this site is increased certainty of positioning. In comparison, septal pacing is a relatively heterogenous group of sites from the upper to lower septum. These may be difficult to reliably and accurately determine and describe, and may be the reason for conflicting outcomes reported (9). However, this notwithstanding, a well-placed RV septal lead is the preferred choice of many and has good supporting evidence.  A small study did not show any difference between acute lead parameters of leads placed in the RVOT or on the septum (10). In patients with difficult anatomy such as young adults, children, or congenital heart disease, the Medtronic Select Secure lead system has been shown to aid selective site pacing away from the RV apex (11). This 4 French lead is catheter delivered with a choice of fixed-shape or steerable catheters available.

One notable exception exists where an apical position is preferred: dual chamber pacing with a short AV delay in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction, where the promotion of dyssynchrony is desirable. This technique is inferior to myectomy and alcohol septal ablation for the treatment of obstruction, and therefore should only be performed in patients with contra-indication to those therapies, or with a pacing indication (12).

Clinical outcome
Several studies have suggested that chronic RV apical pacing is associated with an increase in heart failure, including in patients with previously normal LV function, and it is widely accepted that RV pacing should be minimised (13-16). However, where this is unavoidable, the importance of pacing site on clinical outcome is less clear. Whilst generally appearing positive, it should be noted that many non-RV apical pacing studies suffer from small sample sizes and variability of percentage of pacing, such that making meaningful conclusions can be challenging, particularly when assessing hard endpoints such as mortality. Although many imaging and haemodynamic studies indicate a benefit of non-RV apical pacing, this does not seem to always extend to exercise capacity, functional class, quality of life, and survival in patients paced at different sites. There is therefore a need for further large well-designed long term RCTs investigating the clinical impact of site-specific non-RV apical pacing.

Cardiac Resynchronisation Therapy / LV pacing: the future for all?
Baseline LV systolic function appears the most important determinant of the risk of deterioration in patients with chronic RV pacing. For patients with severe left ventricular systolic impairment who meet current criteria cardiac resynchronisation therapy (CRT) provides clear morbidity and mortality benefit (17). However, recent RCT evidence has also suggested that CRT should be preferred in patients with mild-moderate LV function (18). Further studies are required before this becomes accepted UK practice, as clearly the cost and infrastructure implications are significant. A randomised trial of 184 patients undergoing an AV node ablation for atrial fibrillation showed an improvement in 6-minute walk test and EF with CRT compared to RV pacing, although this was most clearly demonstrated in those with mild-moderate LV function (19). It may be therefore that future discussion of optimal RV pacing site becomes academic, with the inexorable rise of LV leads. However, the time, cost and complication rate relative to simple RV pacing is likely to remain prohibitive for some years.

Trainee Perspective
Having the opportunity to operate with multiple implanters during cardiology training is invaluable, as inevitably different tips and tricks can be learnt from individuals that serve to shape one’s own technique. This is particularly true of pacing at sites other than the apex, and there is a learning curve with each.
All major device companies run training courses, which can be a useful way to familiarise oneself with specific kit and programming. As with most interventional procedures, volume of cases will inevitably expose the operator to those with increased complexity. Most implanters even at a senior level would agree there is nearly always something that can be learnt in pacing, particularly CRT as rarely are two cases the same.
Active involvement in the programming of the device at implant is encouraged, as is attendance at follow up clinics. Device accreditation with the BHRS or other specialist body is an excellent way to improve understanding, and hopefully, patient outcome.

Trainees should be encouraged to become familiar with the techniques involved in non-RV apical pacing, which are entirely feasible and do not add to the complexity of cases. It is clear that no study demonstrates inferiority of non-RV apical pacing whilst many data point to the contrary. In parallel, the number of indications and patients eligible for CRT is likely to continue to rise. In the majority of brady pacing cases, particularly in patients with any degree of LV dysfunction, the weight of evidence suggests that non-apical RV pacing should be preferred.

Figure 1 (7).
Illustration of the heart highlighting the RV septal anatomy.

The RVOT is bordered by the pulmonary valve above and the superior aspect of the tricuspid apparatus below (both dotted lines). The upper part of the septal wall is the conus arteriosus, bordered below by the supraventricular crest. To the anatomical left of the septomarginal trabeculation, which continues into the moderator band, are the septoparietal trabeculations. These structures have been emphasised in this illustration.

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