Finding the Sweet Spot for Non-Apical RV Pacing — “Love’s Labor’s Lost or Much Ado About Nothing:” A New Angiographic Technique To Accomplish Accurate Physiological RV Septal Pacing in Under 5 Minutes From Venous Cannulation (Or Bust)

Abstract: Right ventricular septal pacing has been long touted as a more physiologic alternative to right ventricular apical pacing. This article reviews the physiologic and clinical evidence for right ventricular septal versus apical pacing, and presents a novel angiographic technique for efficient attainment of the optimal septal pacing site. The reasons for equivocal clinical findings in septal versus apical pacing studies are discussed, and a new strategy for non-apical pacing clinical trial design utilizing comparative anatomic assessment of septal pacing site versus clinical outcome is proposed.   

J INVASIVE CARDIOL 2014;26(3):140-147

Key words: RV septal pacing, RV apical pacing, RV outflow tract pacing

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The deleterious effects of right ventricular apical (RVA) pacing have been extensively chronicled in the pacing literature for over two decades, including dyssynchronous right ventricle (RV) to left ventricle (LV) activation, worsening heart failure, adverse ultrastructural myocardial mechanics, deteriorated LV remodeling and impaired metabolism, worsened LV filling pressures, atrial fibrillation, increased mitral regurgitation, and increased mortality and morbidity.^1-4 Moreover, chronic RVA pacing carries risks of short- and long-term complications, including pain, tamponade from perforation, clinically significant far-field oversensing, or stimulation of extracardiac structures, eg, phrenic or intercostal stimulation. It is therefore worth asking why the predominant practice of RVA lead insertion continues relatively unabated in many countries across the world. The usual reasons cited include: (1) lack of a large randomized multicenter study showing clear mortality or heart failure benefit for non-apical RV pacing (NRVP); (2) concern over septal lead stability and thresholds both short and long term; (3) concern over potential unforeseen late side effects of septal lead implantation, eg, arrhythmias; (4) septal approach perceived to be more time consuming and technically difficult; and (5) inadequate tools, techniques, and reproducibility (both in clinical trials and in daily practice) for obtaining the “sweet spot” in septal pacing with the best physiological response. Indeed, despondency with these issues may have led to apathy or, worse still, the belief that septal/outflow pacing cannot be achieved with any degree of accuracy or reliability to be worth pursuing at all. Thus far, lead stability in the hands of reasonably experienced implanters is excellent, and no unforeseen adverse side effect signal for RV septal pacing in patients with normal LV function has ever been demonstrated.^1,5-7 The data for non-apical and in particular RV septal pacing demonstrate improved LV function, prevention of adverse LV remodeling, and prevention of heart failure. These data stand in stark contrast to the plethora of evidence pointing to the deleterious effects of chronic RVA pacing in patients with normal and especially reduced LV function.^8-12 Believing as physicians, the Hippocratic dictum of primum non nocere, we should at least strive to do no possible procedural harm, and the avoidance of RVA pacing is by current evidence, a giant step in the right direction. The reader is directed to the elegant summary of these arguments by Drs Mond and Vlay (pioneers in the field of septal pacing) in their editorial in the November 2010 issue of PACE titled, “Pacing the right ventricular septum: time to abandon apical pacing;” as well as the excellent contemporary reviews and meta-analysis of the RV non-apical and right ventricular outflow tract (RVOT) septal pacing literature by Da Costa et al and Shimony et al.^1-4 Both conclude in the need for large, long-term randomized controlled trials (RCTs) to assess RVA versus NRVP (see below). The present article focuses on technically enabling those who would accept septal pacing as a worthwhile goal in NRVP, and wish to achieve it with efficiency, accuracy, and long-term success.

Right Ventricular Septal/Outflow Tract Anatomy and Physiology

The anatomical RVOT is defined between the pulmonic valve superiorly, the upper roof of the tricuspid valve apparatus inferiorly, the septum posteriorly and medially, the free RV wall anteriorly, and in between the septum and free wall a small tract of anterior RV wall containing the left anterior descending (LAD) coronary artery (Figure 1A).^13,14 For purposes of pacing the proposed target zone, the septomarginal trabeculations (SMT) in the truly inferior portion of the septal RVOT, or the septal (not free wall) zone bounded by the supraventricular crest, and septomarginal trabeculation are used (Figure 1B).¹³ The zone at or below the level of the moderator band is too close to the apex and the high RVOT septum in the infundibulum/conus arteriosus is smooth walled and yields poor attachment of leads and high pacing thresholds. 

Using electrocardiographic (ECG) imaging, in which a 224 ECG map of the entire torso surface is
anatomically coupled to a high-resolution computed tomography (CT) scan image of the heart, Ramanathan et al mapped the earliest cardiac electrical activation sequences, finding a general sequence of activation common to humans that involves earliest epicardial activation in the right paraseptal region and multiple breakthroughs aligned parallel to the course of the LAD (Figure 2).¹⁵ The “septoparietal/septomarginal target zone” for non-apical RV septal pacing is proposed on this anatomical-physiological basis.

Modified Mond Lead Placement Technique

Delivery of pacing leads from a subclavian approach via the SVC requires a stylet shaped with primary and secondary curves. The primary curve is required to traverse the tricuspid valve toward the RVOT away from the apex, and a secondary posteriorly directed curve then redirects the lead toward the septum away from the anterior free wall (Figures 1C and 1D). These features were identified by Vlay and modified by Mond, who has validated the use of this stylet in a large case series.^5,6,16 While this stylet shape can be produced manually, the commercial availability of the Mond stylet (St Jude Medical, Inc) has resulted in greater ease, accuracy, and reliability in septal lead delivery (Figure 3). The primary curve is simple and serves to deliver the lead to the septal/outflow vicinity, while the posterior directionality of the secondary curve steers the lead away from the free wall toward the target zone septomarginal trabeculations (SMTs) that offer a stable implantation site (Figures 1C and 1D). Using a three-dimensional shape similar to the Mond style, and a right anterior oblique (RAO) fluoroscopic grid target site, Burri et al showed that a 97% success rate for mid-septal positioning could be achieved (using echocardiography for confirmation of location), versus an 45% success rate using a two-dimensional shape (Vlay-S type with no posterior bend) and no RAO grid target site overlay.¹⁷ In a contemporary 2013 series of 51 patients, Osmancik et al utilized a manually fashioned three-dimensional Mond-type stylet to deliver pacing leads to a mid-septal fluoroscopic target, and then verified the lead location using 256-slice cardiac CT.¹⁸ They found 59% were in the anterior wall and only 41% were in the true targeted mid-septal location. Clearly, something is missing: either standardization of the stylet shape (rather than manual ad hoc shaping), and/or alternative imaging guidance to the target site is required to reproducibly increase implantation success rates.

In this article, a novel technique is described that ensures highly accurate reproducible lead positioning. This technique relies on anatomical identification of the target zone using limited contrast injection angiography, with only confirmatory reliance on less accurate positional indicators such as the fluoroscopic views or 12-lead ECG vectors.

Novel Angiographically Guided Implantation Technique 

Step 1 (set-up). Separate dual-sheath venous access (presumed to be subclavian for this discussion) is established. Once venous access is established, a simple curved soft stylet is placed in the pacing lead, and the ventricular lead is delivered using one of the two sheaths, through the tricuspid valve toward the RVOT and then across the pulmonic valve into the left or right main pulmonary artery. A longer-length lead with sufficient slack allows prevention of lead prolapse during stylet exchanges, as described below. This is particularly important in cases of tortuous venous anatomy, large RV size, and large body size (Figure 4A).

Step 2 (stylet exchange). The simple curve is exchanged for the dual-curve Mond stylet (St Jude type). A soft stylet and careful advancement techniques are suggested until the Mond stylet is placed fully in the lead, which still rests in the pulmonary artery (PA). 

Step 3 (mapping the target zone). A balloon flotation end-hole injection catheter (eg, coronary sinus injection catheter) is advanced with balloon inflated into the main PA across the pulmonic valve. A 10 cc luer-lock syringe with 70%-100% contrast dilution is attached to the injection port. The catheter is then pulled down to just below the pulmonic valve using a small bolus contrast injection to verify initial position. A pull-back hand injection angiogram is then performed by firmly injecting and simultaneously dragging the balloon catheter (with balloon inflated) from the RVOT down into the RV cavity across the septum (Figure 4B). A roadmap is created of the target zone septoparietal trabeculations (SPTs) and placed on the monitoring reference screen. We perform this pull-back using the anteroposterior (AP) view, but it is best mapped by using an RAO view also. In fact, a “rolling” cine sequence from RAO to LAO (right/left anterior oblique) with sustained injection yields the best three-dimensional visual appreciation of the location of this area. With recurrent practice, only a single confirmatory AP view may suffice if a Mond-type stylet shape and the above pull-back technique are utilized. Alternatively, provided neither the image intensifier nor the table are moved, the target zone can be marked on the monitor screen and used as a guide for step 4 below. A better approach is to access with two sheaths initially, allowing one to be used for balloon catheter introduction and the other for ventricular lead insertion. This also allows verification of lead position or guidance of lead repositioning, if required, by repeat puff contrast injection as shown in Figure 4, inset e.

Step 4 (lead delivery). The Mond stylet preloaded lead is now dragged back from the main PA and is automatically directed toward the septum away from the free wall. With minimal manipulation, the target zone is selected by the lead and screwed into place (active fixation leads are preferred, although passive fixation can also be used) (Figure 4B, insets a and b). If the target zone is not easily selected, the lead is replaced in the main PA and the Mond stylet removed for manual reshaping the primary or secondary curves prior to reintroduction and refixation using the same drag-down procedure described. This can usually be accomplished swiftly in under 5 minutes, which negates the idea of a complex, time-consuming procedure. 

Step 5 (confirmation). Finally, the regular RAO and LAO 40° views and the 12-lead ECG vectors can be utilized to confirm the positioning accuracy. The main points for fluoroscopic evaluation are the septal direction (rightward and posterior pointing directionality toward the spine) of the v-lead away from the anterior free wall in the LAO view (Figure 4, inset d; Figure 5). According to the published literature, ECG vector criteria include:^5,19,20 (1) a vertical frontal axis with deep S in lead I (sometimes equivocal/inferior) and a clockwise rotation of the horizontal axis with tall R-waves in leads V4-V6; and (2) in cases of accidental free-wall implantation, smaller R-waves are seen in V5-V6 and an upright R-wave is seen in lead I. A notched R-wave in lead III is also frequently seen in cases of free-wall pacing (Figure 5).^20,21 Allowing for variations in heart rotation and vertical position in the thoracic cavity, none of these ECG criteria may be failsafe. Burri et al used electroanatomic mapping of the RV to confirm pacing lead location and showed in 31 patients that no single ECG criterion was reliable in distinguishing mid-septal from anterior free-wall locations, and that a negative QRS or Q-wave was in fact more frequent in anterior rather than mid-septal location.^17,21 Thus, where accidental free-wall implantation is suspected by ECG vector analysis, fluoroscopic imaging in a steep LAO or left lateral view helps to confirm this (Figures 4D and 5). 

Alternative Lead Delivery Techniques

An alternative delivery technique using the SelectSecure lumenless, actively fixed, screw-in 4.1 Fr lead and the SelectSite steerable guide or the C315-type, fixed-shape catheter delivery system is available (Medtronic, Inc; Figure 6). There is a significant learning curve, and in our experience has been more cumbersome than the stylet-based approach, which is faster, more convenient, and reproducible. The fixed-shape, peel-away coronary sinus delivery catheter can be used for lumenless lead delivery. However, not all these fixed- or deflectable-type delivery catheters possess the required posterior tip angulation to avoid the free wall (which is crucial for success) and their reproducibility in achieving the target zone for RVOT/mid-septal pacing is not established. In the largest published series of 138 ventricular implants using the SelectSite system, Zanon et al found a 98% success rate in implanting RVOT leads with a mean fluoroscopic time of 19 ± 15 minutes, suffering 1 perforation and 2 acute lead dislodgments.²² As judged by LAO and RAO views as well as ECG vectors, 76% achieved a high RVOT, 6% a free-wall RVOT, and 18% a low septal position.

In contrast to catheter-based techniques, the septal stylet delivery technique has been extensively tested and validated, and is usually achieved with fluoroscopic times well under 5 minutes in experienced hands. In 2006, Vlay described a 9-year experience of 460 patients with RVOT pacing with stylet-driven delivery, with a 92% success rate and only 1 dislodgment, and no significant differences in thresholds for sensing/pacing or lead impedance between apical and RVOT pacing subgroup comparisons.¹⁶ Likewise, Mond and Vlay cite >1200 cases of RV stylet-driven delivery of active fixation leads to the RVOT and mid-septum, with over 90% success, specifically 89% for the mid RV septum and 97% for the RVOT.² A 1%-2% failure rate is seen with immediate postoperative dislodgments (which decreases with experience), and with cases of gross RV enlargement or torrential tricuspid regurgitation. In 2009, Mond reported an RVOT series showing that at 1 year, the average stimulation threshold was 1.5 Volts with 94% of the leads having a stimulation threshold <1 Volt.²³ Moreover, unlike RV apex pacing, complications such as high threshold exit block, diaphragmatic pacing and pericardial pain, and tamponade are all rare to non-existent. 

Septal Defibrillator RVOT Lead Positioning

It should be further noted that the current randomized literature for dual-chamber implantable cardioverter defibrillator (ICD) shows no significant differences in capture, delivery success, or defibrillation thresholds between septal or RVOT defibrillator lead placement versus conventional apical insertion.²⁴ In the largest reported series of 185 patients in the EFFORT registry, using a mixture of devices and leads from Medtronic, St Jude, Boston Scientific, Biotronik, and Sorin, Mascioli et al show similar efficacy and safety between RVOT and RVA ICD placement of defibrillator leads, similar pace/sense thresholds, and similar efficacy in a 14 J shock restoration of sinus rhythm from VF induction.²⁵ RVOT defibrillator insertion with 7-Fr compatible dual-coil leads is easily and reliably achieved in the high mid septal/RVOT locations using the technique described above.

Evidence Favoring Non-Apical RV Septal/RVOT Pacing

(1) Hemodynamics. In a 2003 pooled analysis of 217 patients from 9 studies, de Cock et al reported a significantly better hemodynamic effect of RVOT versus RVA pacing (OR, 0.34; CI, 0.15-0.53), but heterogeneity in pacing effects, sample sizes, chronicity, and assessment methodology were inherent.²⁶ Using invasive measurements of LV and RV systolic and diastolic function, as well as three-dimensional electroanatomic mapping with the CARTO system (Biosense Webster), Vancura et al used a comprehensive mapping protocol in 8 patients comparing single-site endocardial pacing (lateral LV region versus differing RV sites within the three-dimensional RV map), and showed that the best indices of LV systolic/diastolic/pulse pressure function were obtained by pacing the RV at the superior-mid septal segment of the RV (Figure 7).²⁷

(2) Interventricular mechanical synchrony and ejection fraction. Following AV node ablation, Victor et al studied 28 patients and showed narrower QRS, as well as better preserved LVEF than chronic RV apical pacing at 3 months.^9,28 Using RV pacing from the mid-septum and RVOT, Alhous et al have shown improved LVEF compared with RVA pacing and reduced pacing-induced dyssynchrony indices compared with the RVA.⁸ In a longer 12-month study of 60 patients, Wang et al also showed superiority of RVOT versus RVA pacing for LV regional performance, LV global electromechanical delay, and interventricular mechanical delay.²⁹ Interestingly, no difference in EF was seen, suggesting that more long-term evaluations of this parameter are needed beyond ≥1-2 years. In a meta-analysis of 14 RCTs/754 patients, Shimony et al found a better LVEF in non-apical versus apical RV pacing, particularly in patients followed for more than 12 months, and with LVEF ≤40%-45%.⁴ Similarly, Tse et al demonstrated a progressive deterioration between 6 and 18 months of follow-up in incidence of myocardial perfusion defects, regional wall-motion abnormalities, and LVEF for RVA versus RVOT pacing.³⁰

(3) Clinical endpoints. Riahi et al used the DANPACE study cohort of 1415 patients with sick sinus syndrome randomized to AAIR versus DDR pacing to investigate the occurrence of heart failure in >5 years of follow-up.³¹ These authors were unable to demonstrate any correlation between the incidence of heart failure and percent V-pacing or lead location (apical versus non-apical). However, heart failure was clinically determined, lead location was non-randomized, and neither serial echocardiography nor BNP corroboration of heart failure status was available. Moreover, a single frontal plane fluoroscopic view was used to determine lead positioning, with no other imaging confirmation of lead position. Thus, while the DAVID and MOST trials have demonstrated increased risk of heart failure hospitalization and/or death from increased burdens of RV apical pacing, the opposite demonstration of benefit of non-apical (specifically, septal or outflow tract) pacing has been confounded by critical methodological deficiencies and lack of sustained follow-up. Despite much anticipation, after almost 5 years and after completion of recruitment, we still await the results of two alternative-site multicenter randomized pacing trials:³² (1) the PROTECT-PACE (The Protection of Left Ventricular Function During Right Ventricular Pacing) trial, initiated in 2007, comparing RV apical versus high septal pacing for primary EF and secondary heart failure/arrhythmia endpoints;³³ and (2) the RASP (Right Apical Versus Septal Pacing) trial, initiated in 2005, comparing RV inflow tract septal versus apical or EF primary and mortality, arrhythmia, and heart failure with 6-minute walk QoL endpoints.³⁴ The OPTIMIZE-RV trial of mid-septal versus PV apical pacing, which was initiated in 2007, has been terminated for speculated reasons of lack of recruitment or perhaps methodological issues.³⁵ The lack of well-derived clinical outcomes data renders definitive conclusions impossible, but encouraging data are now emerging. Using a double-blind randomized design and a cohort of 142 patients with advanced atrioventricular block, Molina et al elegantly demonstrate 1-year data showing superior and significant improvements in LVEF, 6-minute walk distance with septal vs apical RV pacing.³⁶

Cardiac Resynchronization Therapy

Only a few studies have examined the role of RV lead position in the efficacy and outcome of cardiac resynchronization therapy (CRT). In a single-blind prospective randomization of 53 patients to RV septal versus RV apical lead positioning guided by RV mapping to obtain maximal electrical separation (MES) between the LV and RV leads, Miranda et al elegantly show at 3 months that the RV-LV MES was greatest in septal locations and corresponded to a greater percentage of CRT responders, as judged by EF 6-minute walk test, with no adverse safety issues.³⁷ The SEPTAL-CRT study, comparing mid-septal RV lead CRT, has completed recruitment but has not yet reported results for 12-month clinical endpoints. In other studies, Kristiansen et al have shown similar reverse remodeling and reversal of LV dyssynchrony at 6 months between RV apex and high posterior septal RV implant as adjudicated by orthogonal view fluoroscopy.³⁸ The confounding effects of possible RV lead displacement and discordant LV lead placement make interpretation difficult due to anatomical factors. In a randomized design in 33 patients with classical CRT indications, Rönn et al could not show a difference between apex and RVOT RV lead positioning in endpoints of EF, QoL, peak oxygen uptake, BNP, or 6-minute walk.³⁹ The single adverse signal of non-apical RV lead location in CRT comes from a retrospective analysis by Kutyifa et al, who used the MADIT-CRT database to show that an excess of the endpoint of either VT/VF or VT/VF/death was ascribed to non-apical RV lead location with no difference in the primary endpoints of heart failure or death.⁴⁰ Clearly, more prospective randomized data with appropriate methodology are needed.

Alternative Imaging Modalities to Confirm/Guide Implantation Site

Echocardiography can be used to locate RV pacing sites (Figure 8) and to assess the dyssynchrony associated with pacing from these sites. However, such evaluations are difficult to achieve intraprocedurally with sterility in the operating room or catheterization laboratory, and are also more time-consuming and expensive in terms of equipment and personnel. Using speckle-tracking global longitudinal strain assessment (important predictor of outcome in chronic LV dysfunction), Inoue et al showed that QRS width and both longitudinal and radial strain indices of dyssynchrony were worse in the apical versus septal pacing location.^41,42 Lastly, while three-dimensional echo and intracardiac echo are promising in the visualization of putative RVOT septal pacing sites, the resolution of three-dimensional imaging is a work in progress, and the time/expense and cumbersomeness of both techniques are prohibitive on a routine basis.^43,44 The resolution of contrast angiographic techniques and cardiac CT for localization is clearly superior and more facile to achieve.¹⁴

Summary

In addition to being intuitive, convenient, and fast, the anatomical identification of the septoparietal and septomarginal trabecular zone of the RV septum by contrast angiography offers two major advantages: (1) a high-resolution target image for accurately  manipulating the RV lead to the desired location; and (2) avoids reliance on fluoroscopic views and ECG vectors, which are useful as confirmatory techniques, but have significant fallibility in identifying accurate septal versus free-wall or even mid versus high septal positioning. The disadvantage of using a balloon catheter and 10-15 cc of contrast seems small in comparison to the advantages offered. I suggest that a Mond stylet and RVOT angiographic mapping be prospectively tested for accurate anatomical positioning using a “gold standard” imaging technique, such as cardiac multislice CT (or cardiac MRI for MRI-safe devices). Because of the complete three-dimensional dataset available, reconstruction in any desired view is feasible (Figures 1E and 1F), scanning time is fast for cardiac CT, the scan is gateable with a regular rhythm (paced or otherwise), and the radiation dose may be limited by using the smallest scan window between the pulmonic valve superiorly and the RV apex inferiorly. Moreover, LV and RV function can be quantitated using CT or MRI.¹⁴ The elegance of such an approach is that, for the first time, it will allow the clinical endpoints to be exactly analyzed according to the anatomical site of lead insertion. In fact, predicting the best physiologic response to non-apical septal or RVOT pacing is predicated on accurately and reproducibly finding the best target zone for pacing. Many of the equivocal studies for long-term RV septal or outflow tract (versus RV apical) pacing have been attributed in significant degree to the improper localization of septal leads, particularly when the mistaken implantation occurs in the anterior free wall.³² In this case, the old real estate maxim of “location, location, location” holds never truer. 

Proposed Future Pacing Trial Design

A long-term multicenter randomized clinical study that uses image-guided lead implantation (perhaps using RV contrast injection), followed by accurately anatomic verification of the implant site (CT offers the best three-dimensional resolution) is desperately needed for the pacing community to convince reluctant adopters of RV septal (non-apical) pacing. Consistency will be obtained by using a Mond-type stylet driven RV septal implantation to achieve the right location, and then compared to true RV apical pacing, using fixed AV synchrony in patients with at least 40% requirement for pacing, despite optimization of the RV pacing mode algorithm. Hard clinical endpoints, such as exercise capacity, heart failure, and quality of life, will be needed as much as physiologically derived hemodynamic surrogate endpoints, such as ejection fraction or synchronicity indices. While methodological finesse based on more complex electroanatomic mapping techniques offers clear improvements in pacing site selection physiologically, it is much more difficult to implement these techniques in the world-wide clinical community of pacemaker implanters, who are mostly non-electrophysiologists.⁴⁵ The radiation dose for the CT study would be limited by restraining the scan window to between the pulmonic valve and the RV apex.

A spectrum of overlapping pacing applications has now developed between: (1) those best served by RV pacing from non-apical sites who have relatively well preserved or normal LV function (LVEF >40%); (2) those with reduced LV function (LVEF <40%) and indications for bradycardia pacing, but not defibrillator therapy; and (3) patients with diminished LV function and established indications for re-synchronization (CRT) and/or defibrillator therapies. Recently, the BLOCK HF study suggested a role for CRT (as compared with conventional RV apical pacing) in patients with heart failure, LVEF <50%, and advanced AV block, by reducing a triple endpoint of death/heart failure visit/increase in LV end-systolic volume index.⁴⁶ Seventy percent of the patients in this trial received pacemakers rather than ICDs; of these, the average QRS was ~125 msec, with mean LVEF of 43%, and 43% of patients with neither LBBB nor RBBB. The benefit of CRT versus selective site RV pacing in such populations remains unclear, particularly when one considers the excess morbidity/mortality of CRT in narrow complex QRS pacing (QRS <120 msec; EF <35%), as found in the recently published ECHO-CRT trial.^47-49 Overall, ECHO-CRT showed a 6% rate of adverse events, including lead dislodgment, lead damage, pacing failure infections, and inappropriate tissue stimulation, was found.⁴⁹ Nor does this factor in the additional cost and expertise required for CRT utilization. In a prospective randomized study of 85 patients with echo speckle tracking analysis to determine LV dyssynchrony, and fluoroscopically guided RV-high septal lead placement, Kristiansen et al showed similar LV reverse remodeling and LV reverse dyssynchrony at 6 months comparing apical and high RV septal RV lead locations (the concordance of the LV lead to its ideal target zone and the resultant CRT benefit remain a confounding factor in analysis of this trial).³⁸

In summary, non-apical RV pacing from sites such as the septoparietal trabecular zone of the RV septum may offer a physiologically beneficial, if not safer and superior alternative to RV apical pacing, particularly for those patients with high-grade AV block and >40% ventricular pacing dependency, with relatively well preserved LV function (EF >40%). Unfortunately, all prior chronic studies with clinical outcomes have not been definitive, because they have not been long enough in duration, nor had suitable imaging direction for implantation or accurate anatomical verification of implant location.^1,32 In the near future, the ideal choice for pacing with significant dependency in patients with preserved LV function may be between physiologically optimized biventricular pacing versus anatomically optimized selective  site RV (mid-septal or RVOT) pacing. The perfection and simplification of leadless pacing and electroanatomic mapping techniques will go a long way toward optimizing selective site RV and LV pacing. Until such time as techniques are perfected, and/or definitive studies are accomplished, “killing them softly”⁵⁰ by RV apical pacing should no longer be an advocated or pursued option. Every pacemaker implanting physician will have to confront the burning philosophical question of apical versus non-apical RVOT pacing: Is it better to do presumptive good and await further definitive data or pursue a path of self evident harm?

Acknowledgments. The author gratefully acknowledges the invaluable and unstinting bibliographic assistance of Nancy Crossfield, MALS, AHIP and Roberta Cavanaugh of the Owen Library Staff, St Agnes Hospital, as well as the support and invaluable technical assistance of the staff at St Agnes Medical Center Cardiac Catheterization and EP Laboratories.

Supplementary Video available at www.invasivecardiology.com

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