Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure patients with severely obvious left ventricular ejection fraction (LVEF) and evidence of cardiac dyssynchrony.1-3 With conventional biventricular stimulation, notable left ventricular (LV) reverse remodeling, the most reliable predictor of long-term survival in CRT patients, is achieved in only 60%-70% of the patients.4,5 Lack of LV dyssynchrony, non-optimal position of the LV pacing lead, high-myocardial scar burden, and sub-optimal device programming have been related to non-response to CRT.6-8 Particularly, the optimal placement of LV lead in a tributary of the coronary sinus is one of the most challenging technique of CRT device implantation. This article will discuss the effect of ventricular leads on the clinic outcome after CRT and how to locate the optimal ventricular leads to maximize the haemodynamic benefits of CRT and provide superior long-term outcome.
LEFT VENTRICULAR LEAD LOCATION AND ITS RESPONSE TO CRT
It was proved that the apical placement was associated with a 64% elevated risk of heart failure or death compared to other locations for the LV lead according to an analysis of data from the MADIT-CRT trial. Mortality alone was 2.59 times higher with apical versus non-apical placement.9 Preferential positioning of LV leads in the basal/midventricle segments may improve outcomes, as the apical LV lead placement is associated with worse CRT outcomes. LV leads positioned in the apical region were associated with an unfavorable outcome, suggesting that this lead location should be avoided in CRT.
A variety of coronary veins are employed for the LV lead: in the Easytrak Registry, 67% of LV leads were placed in the lateral or posterior coronary veins;10 and Molhoek et al11 reported that 35% were placed in posterior veins and 28% in lateral veins. When coronary lead position is reviewed in the context of area of latest LV myocardial activation, LV lead tip concordance to, or in the vicinity of, the region with maximal delay was seen in only 64.8% (35 of 54) and 55.2% (32 of 58) patients, respectively.12-15 We found that the improvement in NYHA class was significantly greater in the anterolateral (AL) vein and posterolateral (PL) vein locations than in the anterior location, while no significant difference in the change of LVEF and left ventricular end-diastolic dimension (LVEDD) after CRT among aterior, antrrior-laterial, posterior-laterial, and posterior lead locations (Figure 1).7 The COMPANION trial also showed similiar result from the acute data, while the chronic data suggested that positioning an LV lead in an anterior rather than a lateral or posterior LV location has similar benefit.
One study16 showed that the responder rate was not inferior when the LV lead was implanted at the anterior or anterolateral wall. MADIT-CRT trial also demonstrated that there was no difference in volume reduction or increase in LVEF between the various LV lead positions.17 Thus, in case of failed implantation at the recommended site, positioning the LV lead in a more anterior location appears to be a reasonable alternative.
We found that the Kaplan-Meier survival estimate at four years varied for location: AL 72%; anterior 48%; PL 62%; and posterior 72% in our study with 457 recipients of CRT.7 Furthermore, in MADIT-CRT trial, it was proved that there was no difference in the estimate of survival free of heart failure or death between leads positioned along the anterior, posterior, or lateral wall, excluding the apical position (unadjusted P=0.65 by the log-rank test). And there was a significant difference in the estimate of survival free of heart failure or death between the LV leads positioned in the apical versus the nonapical location (unadjusted P <0.01) by the log-rank test (Figure 2).9
RIGHT VENTRICULAR-LEFT VENTRICULAR INTERLEAD LOCATION AND ITS RESPONSE TO CRT
The optimal right ventricular (RV) pacing lead location for CRT remains controversial. One study did not show any difference between RV apex (RVA) and RV high septum (RVHS) pacing sites in terms of overall improvement in clinical outcome.18 However, the effect of RV lead location on CRT response varies depending on LV stimulation site. When the significance of RV lead location was assessed in individual LV segments, RVA pacing produced clinical, echocardiographic, and neurohormonal responses similar to RVHS pacing in combination with lateral cardiac vein (LCV) stimulation. RVA pacing was more efficacious than RVHS pacing when used in combination with anterolateral cardiac vein (ALCV) site, and RVHS pacing was superior to RVA pacing in combination with posterolateral cardiac vein (PLCV) site.
There were limited data regarding the optimal RV lead pacing location in patients who underwent CRT.18-21 The available studies had mainly evaluated acute haemodynamic changes and/or QRS duration in relation to the RV lead position. Leclercq et al20 defined optimal biventricular pacing mode by the degree of QRS narrowing and found that biventricular pacing with the RV lead inserted in the RV outflow tract was superior in 11 patients (61%) and in RVA in the remaining seven (39%) patients. The importance of RV-LV interlead distance in predicting the acute haemodynamic response to CRT has been also evaluated in a radiographic study.22 The horizontal component of the LV-RV interlead distance on the lateral chest radiograph was greater in acute responders to CRT compared with non-responders.
The idea that RVHS pacing may offer more beneficial effects than RVA during biventricular pacing is based on the prior studies that explored alternative sites for univentricular RV pacing.23,24 These data suggested that RVA pacing might be detrimental to LV function, presumably because bypass of the His-Purkinje system produces dyssynchronous LV contraction. Results of acute haemodynamic studies, although controversial, have shown increased cardiac output as a result of RVHS pacing, relative to RVA pacing.25 However, no symptomatic improvement or haemodynamic benefit was noted after three months of RVHS pacing, in comparison with RVA pacing.26
Therefore, it shows that RV lead location is not an important determinant of CRT response when LV can be stimulated from the LCV. However, optimization of the RV lead location should be an important consideration when it is not possible to place LV lead in the LCV. In patients with a concordant LV lead position, the RV lead position appears to make no difference in the response to CRT. However in patients with a discordant LV lead position, an RVS lead position is associated with better LV reverse remodeling. These findings suggest an important role for the RV lead position only in patients with a suboptimal LV lead position.
DUAL-SITE LV CRT
The triple-site biventricular pacing in heart failure (TRIP-HF) study was a single blind randomised crossover comparison of the clinical and mechanistic effects of triple-site biventricular pacing (TSVP) versus standard biventriculr pacing (SBVP) during two periods of three-month each. Chronic TSVP is technically feasible. A significant improvement in LVEF was observed with TSVP, but without detectable benefit in clinical status during the three months follow-up time. Further and larger clinical studies are needed to evaluate the real clinical relevance of this new CRT modality.27 Dual-site LV pacing was associated with a greater NYHA class reduction, and larger increases in VO2 max and 6-minute walking distance after three months of follow-up.28 A significant favourable effect was observed on LVEF and intra-ventricular LV synchrony, but not on interventricular synchrony and QRS duration.
Padeletti et al29 found that dual-site LV CRT did not further improve acute haemodynamic indexes compared with the best single-site LV CRT configuration with optimized AV delay. The triple-site cardiac resynchronization study of patients with heart failure (TRUST CRT) showed that this form of pacing is equally safe and feasible as the conventional CRT.
The RV lead position, either RVA or RVHS appears to make no difference in the response to CRT but the LV lead placement play a vital role.9,30 The latest activated regions of LV or areas without transmural myocardial scar for an optimal CRT are preferred. Currently, data demonstrate that no significant difference of clinical outcomes in posterior, anterior, and lateral LV lead position was found, while the ideal pacing site of the LV should be avoided in the apex position as suggested in COMPANION trial and MADIT-CRT trial. And dual-site LV CRT, which is a new technique, is also still in progress and we are looking forward to getting more updates from that.
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