Lead positioning for cardiac resynchronization therapy: techniques and priorities

Transcription

1 Europace (2009) 11, v22 v28 doi: /europace/eup306 Lead positioning for cardiac resynchronization therapy: techniques and priorities John M. Morgan*,1 and Victoria Delgado 2 1 Wessex Cardiac Centre, Southampton University Hospitals, Southampton, UK; and 2 Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands Although cardiac resynchronization therapy (CRT) has demonstrated to be an effective treatment for heart failure patients, up to 30 40% of the patients do not show a favourable response. Implantation of the left ventricular (LV) pacing lead is one of the determinants of CRT response. This procedure includes several challenging technical issues and strongly depends on the highly variable anatomy of the coronary sinus and tributaries. In addition, the final position of the LV pacing lead may target the latest activated areas of the left ventricle in order to obtain effective resynchronization. Furthermore, the presence of transmural myocardial scar at the region targeted by the LV lead may also determine the response to CRT. This review discusses all the issues related to LV lead implantation and the role of multimodality imaging to anticipate the implantation strategy. Finally, alternative LV pacing sites and their effect on clinical outcome and LV performance will be discussed Keywords Cardiac resynchronization therapy Pacing Endocardial Epicardial Coronary sinus Introduction Cardiac resynchronization therapy (CRT) restores the synchronicity of the atrio-ventricular, interventricular, and intraventricular contractions and results in improved clinical outcome and cardiac performance of advanced heart failure patients with wide QRS complex. 1 However, a significant percentage of patients treated with CRT (up to 40%) do not show an improvement in clinical symptoms or cardiac function. 2 Lack of left ventricular (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. 3 Particularly, the optimal placement of an LV lead in a tributary of the coronary sinus is one of the most challenging technical aspects of CRT device implantation. Technically, the final position of the LV pacing lead depends on the anatomy of the cardiac venous system, the performance and stability of the pacing lead, and the absence of phrenic nerve stimulation. 4 However, an optimal LV lead position may theoretically be defined by the positioning of the LV pacing lead coincident with the latest activated areas of the left ventricle, since that location maximizes the haemodynamic benefits of CRT and provides superior long-term outcome. 5 7 The presence of suitable tributaries of the coronary sinus in the latest activated areas of the left ventricle is therefore mandatory. In addition, the presence of myocardial scar at the area targeted by the LV pacing lead is an important determinant of CRT response. 8 When the LV lead is positioned at an area with transmural scar, the beneficial effects of CRT on clinical outcome and cardiac performance may be reduced. 8 Therefore, an integrated evaluation of candidates to CRT, including the assessment of all these three factors (latest activated areas of the left ventricle, presence of suitable tributaries, and evaluation of the location and burden of myocardial scar), is crucial to achieve a high favourable response rate and an improved clinical outcome. However, other several technical issues on LV pacing lead implantation remain controversial. To date, the LV pacing lead is conventionally positioned in epicardial locations. Endocardial LV pacing may provide a more physiological electrical activation and more homogeneous LV resynchronization than epicardial LV lead pacing. 9 Furthermore, initial experiences have demonstrated the superior beneficial effects of LV pacing in multiple sites when compared with single site LV pacing. 10,11 The present article reviews the state-of-the-art CRT device implantation, addressing the technical issues crucial to achieve the highest CRT response rate and how multimodality cardiac imaging may help to anticipate the LV pacing lead implantation strategy. In addition, the potential clinical benefits of alternative locations of the LV pacing lead will be discussed. Conventional cardiac resynchronization therapy After conventional implantation of the right ventricular and the right atrial (if the patient is in sinus rhythm) leads, implantation of the LV pacing lead is usually performed by a transvenous approach, cannulating one of the tributaries of the coronary * Corresponding author. Tel: þ jmm@hrclinic.org Published on behalf of the European Society of Cardiology. All rights reserved. & The Author For permissions please journals.permissions@oxfordjournals.org.

2 LV lead position in CRT v23 sinus. The different procedural steps are usually straightforward and, once the vascular access is obtained, the proximal coronary sinus is intubated with a guiding sheath and the pacing lead is advanced through this to a second- or third-order branch of the coronary sinus to pace the LV lateral wall. However, procedural feasibility depends on variations of venous anatomy and some technical factors such as accessibility of the vein, pacing threshold, lead stability, and phrenic nerve stimulation. Table 1 summarizes the common causes of procedural difficulties and the manoeuvres to overcome them. Table 1 Technical difficulties to implant the left ventricular pacing lead and potential solutions Difficulty Reason of difficulty Solution... Accessing the coronary sinus Prominent sub-eustachian pouch Use a large curved guiding sheath balanced on high right atrium Deflectable catheter with back bend moved into the coronary sinus from higher interatrial septum Prominent thebesian valve Enter from inferior and ventricular portion where the thebesian valve is less prominent Guide-wire and balloon dilatation of the coronary sinus Large left ventricle Remember that the angle between the coronary sinus and the inferior silhouette becomes larger Large right atrium Use large curved guiding sheath Looping of large curved deflectable catheter and using back bend to probe septum for coronary sinus Find the fosa ovalis or bundle of His, working inferiorly to reach the coronary sinus from the roof Advancing within the coronary sinus Placement of the LV pacing lead on the lateral wall Stenosis/spasm Valves in the coronary sinus Excessive tortuosity Subselection of an atrial vein by a leading catheter Lead instability Absent lateral veins Extensive myocardial scar (increased thresholds or capture latency) Small lateral ventricular veins Variceal veins Phrenic nerve stimulation Pass the guide-wire and perform low-pressure balloon dilatation Subselection of lateral branches of the proximal posterior vein Use stiffer guide-wire Use deflectable catheter to open a semi-occlusive valve Subselection of lateral branches of the proximal posterior vein to access the lateral wall Use soft guide-wires with constant venography Understand atrial and ventricular orientation of lead/wires/ catheters in the right anterior oblique orientation Wedging lead into a second-order branch Understand fluoroscopic appearance of under- and over-slacked leads Use second- and third-order branches of veins to produce U-shaped or L-shaped lead tip Use posterior or anterior veins and subselect anastomotic branches that drain the lateral wall Use middle cardiac vein Maximize tissue contact Place the lead slightly antero-lateral or postero-lateral to the scarred lateral wall Use anastomotic branches or second-order branches from antero-lateral or postero-lateral circulation Use larger stylet-driven leads Use larger over-the-wire leads with prominent proximal corkscrew curvature Subselect second-, third- or fourth-order branches until smaller veins are reached Change configuration options Avoid repositioning the LV lead in the same main venous branch Avoid using lower output but rather repositioning the lead in another ventricular vein Adapted from Asirvatham (2007). 32 LV, left ventricle.

3 v24 J.M. Morgan and V. Delgado Beyond these technical issues, the final goal in LV pacing lead implantation is to achieve theoretically the region of latest intrinsic activation, since this position maximizes the haemodynamic and clinical benefits of CRT. In clinical practice, the LV pacing lead is positioned as far as possible from the right ventricular pacing lead, commonly the lateral or postero-lateral wall of the left ventricle. An integrated evaluation including the assessment of the latest-activated regions of the left ventricle, the assessment of the venous anatomy and studying the presence of myocardial scar in those regions is crucial in the patient selection and may improve the favourable response rate. Assessment of latest activated areas of the left ventricle Several algorithms based on intracardiac electrocardiograms have been proposed to guide LV lead positioning. 12 Singh et al. 12 studied 71 patients undergoing CRT device implantation. The LV lead electrical delay was measured during the procedure from the onset of the surface electrocardiogram QRS complex to the onset of the sensed electrogram on the LV lead, as a percentage of the baseline QRS complex. The longest LV lead electrical delays were related to superior acute LV haemodynamic improvements, whereas LV lead electrical delays,50% were related to a worse clinical outcome (hazard ratio: 2.7; 95% confidence interval: ; P ¼ 0.032). 12 In addition, several invasive and non-invasive imaging techniques have been proposed to identify the latest activated areas of the left 6,13 17 ventricle. Three-dimensional non-contact LV endocardial mapping provides exact characterization of the LV activation sequence, indicating the latest activated LV regions where the LV pacing lead should preferably placed (Figure 1). Fung et al. 6 evaluated the LV activation pattern in seven heart failure patients with left bundle branch block on surface electrocardiogram. By using three-dimensional non-contact LV endocardial mapping (EnSite 3000, Endocardial Solutions, Minneapolis, MN, USA), a high variability on LV activation pattern was demonstrated and, particularly, three patients showed homogeneous activation sequence within the left ventricle despite left bundle branch block on electrocardiogram. In contrast, the other four patients showed a heterogeneous LV activation with the posterior and lateral wall as the most delayed areas. These findings were extended by Lambiase et al. 7 in 10 patients treated with CRT. By using the three-dimensional non-contact LV endocardial mapping system, the LV activation pattern was evaluated in different pacing modes (DDD-right ventricular, DDD-LV, biventricular pacing) and sites. These LV activation patterns were related to changes in LV haemodynamics (cardiac output and dp/dt max ). With biventricular pacing and pre-stimulation of the left ventricle at the latest activated regions, the acute improvements in LV haemodynamics were maximized. 7 The assessment of the latest activated LV areas can be also performed non-invasively by using echocardiographic techniques, such as tissue-doppler imaging or two-dimensional speckle tracking imaging, and tagged magnetic resonance imaging. 5,16,17 Ansalone et al. 5 demonstrated the role of echocardiographic tissue-doppler imaging to identify the most delayed LV regions and to evaluate the effect of CRT on LV performance according to the LV lead position (at the latest activated areas or at remote areas). In 31 heart failure patients treated with CRT, tissue-doppler imaging demonstrated that the most frequent latest activated areas were the lateral (35%), anterior (26%), and posterior (22%) regions. The LV pacing lead was preferably positioned in the lateral (35%) and posterior (32%) regions and 42% of the patients were paced at a concordant site. These patients with a concordant LV lead position showed the greatest improvements in clinical status and LV performance. 5 Recently, two-dimensional speckle tracking echocardiography has been proposed as a valuable imaging tool to characterize the LV mechanical activation pattern and to identify the most delayed activated LV regions. 13,17 This echocardiographic imaging technique evaluates the active myocardial contraction in three orthogonal directions (radial, circumferential, and longitudinal). The longest series evaluating the role of this technique to identify the latest activated LV areas included 244 heart failure patients treated with CRT. 17 On the basis of radial strain time curves obtained at the mid-ventricular short-axis images of the left ventricle, the most frequent latest activated areas were the posterior (36%) and the lateral (33%) regions (Figure 2). In 63% of the patients, the LV pacing lead was placed at the latest LV-activated region. When compared with patients with a Figure 1 Three-dimensional non-contact LV endocardial activation mapping. Example of a patient with dilated cardiomyopathy (LV ejection fraction 30%) and QRS complex duration of 154 ms. The three-dimensional non-contact LV endocardial activation mapping shows the propagation of the activation wavefronts with an anterior conduction block resulting in delayed activation of the lateral wall. The virtual electrograms over the line of block are displayed in the left panel. The LV lead was positioned at the basal lateral region (white arrow). Adapted with permission from Bax et al. 33

4 LV lead position in CRT v25 Figure 2 Two-dimensional speckle tracking echocardiography to identify the latest activated areas of the left ventricle. From the midventricular short-axis view (A), two-dimensional speckle tracking analyses LV radial strain. The short-axis view is divided into six segments (antero-septal, anterior, lateral, posterior, inferior, and septal). The radial strain time curves are displayed in (B) and the latest activated areas can be identified as the areas with the latest peak radial strain. In this example, the latest activated areas are the posterior and lateral segments (green and purple arrows), whereas the antero-septal and septal segments are the earliest activated segments (yellow and red arrows). Figure 3 Tagged magnetic resonance imaging to characterize the LV mechanical activation sequence. Tagged magnetic resonance imaging permits the evaluation of myocardial deformation in three orthogonal directions (radial, circumferential, and longitudinal) (A). The individual phases from the cardiac cycle show the spatial and temporal evolution of three-dimensional circumferential strain (B). By colour-coding the temporal evolution, the latest activated areas of the left ventricle can be identified. Adapted with permission from Lardo et al. 16 discordant LV lead position, patients with concordant LV lead position showed an improvement in LV performance and had a superior long-term outcome with an event-free survival rate of 78% vs. 57% at 3-year follow-up (P ¼ 0.022). Finally, tagged magnetic resonance imaging is a three-dimensional imaging technique that permits characterization of LV mechanical activation sequence and detection of the latest activated segments (Figure 3). 16 Several methods and indices based on tagged magnetic resonance imaging have been proposed to quantify LV dyssynchrony. 16 All of them evaluate the LV shortening in the circumferential and longitudinal directions or the thickening in the radial direction. Particularly, the assessment of LV circumferential shortening provides superior accuracy than longitudinal shortening to predict favourable response to CRT. 15 Despite recent technical advances, this imaging technique is not widely available and incompatible with the CRT devices, limiting the evaluation of the effects of CRT on LV performance at follow-up. Assessment of cardiac venous anatomy The most common approach to evaluate the cardiac venous anatomy uses fluoroscopy just prior to implantation of the LV pacing lead. With the use of a balloon occlusion catheter located

5 v26 J.M. Morgan and V. Delgado in the proximal coronary sinus, coronary venography can be obtained (Figure 4A). This imaging technique permits identification of potential anatomic factors that may pose difficulties to cannulate and advance the LV pacing lead, such as valves at the ostium of the ventricular veins, variceal veins, or absence of lateral vein. Particularly, to anticipate whether the LV pacing lead could be implanted in a lateral vein, the assessment of the cardiac venous anatomy with multi-detector row computed tomography or magnetic resonance may be of value. In patients without suitable postero-lateral veins to host the LV pacing lead, a surgical implantation of the LV lead at the latest activated region may be preferred. In a series of 100 patients, including 34 patients with prior myocardial infarction, van de Veire et al. 18 demonstrated a considerable variation in venous anatomy by using 64-row multidetector row computed tomography (Figure 4B). In addition, the venous anatomy was strongly related to the presence of prior myocardial infarction; patients with previous myocardial infarction had significantly less frequently left marginal veins (Figure 4C). Finally, internal lumen dimensions could be obtained providing non-invasively comprehensive information of the venous anatomy prior to LV lead implantation. 18 Assessment of location and extent of myocardial scar Finally, prior to implantation of the LV pacing lead, evaluation of location and extent of myocardial scar is crucial to achieve a high favourable response rate. The implantation of an LV lead at an area with transmural myocardial scar may result in ineffective CRT. With the use of three-dimensional non-contact LV endocardial mapping systems, LV areas with extensive fibrosis or myocardial scar may be identified as areas of slow conduction. Lambiase et al. 7 demonstrated that positioning the LV pacing lead in areas of slow conduction resulted in prolonged LV activation time and dyssynchrony and, consequently, in less LV haemodynamic improvement. Other non-invasive imaging techniques provide information on myocardial scar burden (myocardial contrast echocardiography, single photon emission computed tomography, contrast-enhanced magnetic resonance) Particularly, contrast-enhanced magnetic resonance provides accurate information on location and extent of myocardial scar. In a series of 40 consecutive heart failure patients treated with CRT, the presence of transmural scar in the LV postero-lateral region was assessed with contrast-enhanced magnetic resonance (Figure 5). 8 Patients with transmural scar in the postero-lateral region did not show clinical or echocardiographic improvement at 6 months follow-up, whereas patients without transmural scar in those regions showed significant improvements in clinical parameters and LV reverse remodeling. 8 Therefore, the integration of information on the latest activated LV regions, venous anatomy, and myocardial scar may refine the patient selection for CRT and, consequently, may increase the favourable response rate. In addition, this information is of value to anticipate the strategy to implant the LV pacing lead (conventional transvenous approach or surgical approach). Surgical left ventricular epicardial lead placement As aforementioned, to achieve optimal biventricular pacing, the LV pacing lead should be placed in the latest activated regions and in areas without transmural myocardial scar. Transvenous implantation of the LV pacing lead faces several technical issues that may reduce the feasibility of this implantation technique. Indeed, up to 8 10% of the patients undergoing CRT device implantation have a failure of coronary sinus cannulation. 4,22,23 Surgical LV epicardial lead placement may then be preferred. Several surgical techniques have been proposed to implant the LV pacing lead: left anterior or lateral mini-thoracotomy, video-assisted thoracoscopy approach, and robotically enhanced telemanipulation systems. With these implantation techniques, improvements in clinical outcome and LV performance have been described at mid-term follow-up without changes in pacing parameters. 22,23 However, limited Figure 4 Invasive and non-invasive assessment of the cardiac venous anatomy with multi-detector row computed tomography. With the use of a balloon occlusion catheter located at the proximal coronary sinus, the tributaries of the coronary sinus can be identified (A). However, the assessment of the venous anatomy can be performed non-invasively with multi-detector row computed tomography (B). With this imaging technique, a high variability in cardiac venous anatomy was demonstrated and, particularly, in patients with prior lateral myocardial infarction, a left marginal vein was lacking in 78% of the patients (C). Adapted with permission from van de Veire et al. 18 and van de Veire et al. J Am Coll Cardiol 2006;48: AIV, anterior interventricular vein; CAD, coronary artery disease; CS, coronary sinus; GCV, great cardiac vein; LMV, left marginal vein; PIV, posterior interventricular vein; PVLV, posterior vein of the left ventricle. *P, 0.001; **P,

6 LV lead position in CRT v27 Figure 5 Evaluation of transmural myocardial scar with contrast-enhanced magnetic resonance. Example of a patient with ischaemic heart failure and extensive transmural myocardial scar located at the infero-postero-lateral segments of the left ventricle (arrow). Adapted with permission from Bax et al. 33 thoracotomy or video-thoracoscopic approaches have targeted the anterior or lateral LV wall to implant the LV lead, whereas robotic technology allows for high-resolution, three-dimensional vision of the ventricular surface. 22 Therefore, the latest activated regions of the left ventricle can be targeted more easily. Finally, surgical epicardial LV lead implantation may be preferred in patients with congenital heart disease in whom the anatomy of the venous system may challenge the transvenous approach. Alternative left ventricular pacing sites In addition to conventional transvenous or surgical LV pacing lead, several alternative pacing sites have been proposed. 10,11,28,29 Specially, endocardial biventricular pacing have provided promising results with superior clinical and LV haemodynamic improvements when compared with epicardial biventricular pacing. 10,11,28 Indeed, endocardial pacing may provide a more physiological electrical activation since electrical depolarization originates in the endocardium and spreads towards the epicardium. 9 In contrast, epicardial pacing reverses the direction of the electrical activation and repolarization with important clinical consequences such as the potential creation of an arrhythmogenic substrate. 9 Several LV endocardial lead implantation techniques have been proposed: transaortic, trans-interventricular septum, transapical, and trans-atrial septum (via mitral valve). 25,26,30,31 The feasibility of LV endocardial lead positioning was reported for the first time by Jais et al. 28 Afterwards, several groups have reported the beneficial effects of LV endocardial pacing on clinical status and LV systolic function. Garrigue et al. 10 compared the effects of epicardial and endocardial biventricular pacing on LV performance in 23 patients. Patients with endocardial biventricular pacing showed significantly greater improvements in LV shortening fraction and stroke volume (Figure 6). In addition, the aortic pre-ejection interval was significantly shorter in patients with endocardial biventricular pacing, probably in Figure 6 Endocardial vs. epicardial biventricular pacing. The acute changes in LV mechanics and haemodynamics with endocardial (Endo, black bars) and epicardial (Epi, grey bars) biventricular pacing are displayed in the bar graph. Endocardial biventricular pacing induced significantly greater increases in LV shortening fraction and stroke volume (indicated by the aortic maximal velocity and the aortic time velocity integral (TVI)]. Adapted with permission from Garrigue et al. 10 *P, relation to a faster impulse conduction in the endocardium than in the epicardium. This results in a more synchronous activation of the left ventricle. These results have been further extended in larger series of patients. 11 Despite these promising results, LV endocardial pacing faces several safety issues such as thromboembolic complications or infection of the endocardial pacing lead. 11 Anticoagulation treatment is required to avoid thromboembolic complications and the maintenance of an international normalized ratio anticoagulation level around (similar to mechanical valvular prostheses) has been proposed. 11 Further studies are warranted to confirm the superiority of LV endocardial pacing over epicardial pacing in providing clinical and LV haemodynamic benefits with a low risk of complications. Finally, triple-site ventricular stimulation has been proposed to improve the clinical and echocardiographic outcomes. 29 A recent multi-centre, single-blind, crossover study enrolled 40 heart failure patients with atrial fibrillation requiring cardiac pacing for slow ventricular rate. 29 CRT device implantation was performed and one lead was placed in the right ventricle and two leads were placed in two different coronary sinus tributaries. After 3 months of follow-up, patients were randomized to conventional stimulation (one right ventricular and one LV leads) or triple-site stimulation (one right ventricular and two LV leads) for 3 months. Afterwards, patients crossed over to the alternate pacing configuration for 3 months more. The implantation of two LV leads was successful in 34 (85%) patients and an acceptable rate of procedural complications was reported. Despite no differences in clinical outcome, triple-site stimulation further promoted a significantly higher increase in LV ejection fraction ( vs %, P ¼ 0.001) and reduction in LV end-systolic volume ( vs ml, P ¼ 0.02) when compared with conventional stimulation. 29

7 v28 J.M. Morgan and V. Delgado Conclusion The implantation of the LV lead position in one of the main determinants of CRT response. Although straightforward, LV lead implantation faces several technical difficulties that may prevent the obtaining of a stable position and good performance of the LV lead without phrenic nerve stimulation. Several manoeuvres have been proposed to overcome those technical issues. In addition, the positioning of the LV pacing lead outside the latest activated regions of the left ventricle or in areas with transmural myocardial scar may result in less than optimal cardiac resynchronization. The assessment of the latest activated areas, cardiac venous anatomy, and location and extent of myocardial scar prior to CRT device implantation is crucial to maximize the benefits of this therapy. In this regard, multimodality cardiac imaging, including invasive and non-invasive techniques, may provide exact and detailed information. In selected patients, surgical epicardial LV lead implantation may be the preferred technique to ensure optimal location of the LV pacing lead. Current technical advances have yielded three-dimensional visualization of the entire LV epicardial surface to surgically implant the LV lead. Finally, alternative pacing sites, such as endocardial LV pacing or triple-site pacing, have been proposed to achieve a high CRT response rate. However, further larger, randomized studies are needed to elucidate the realistic benefits of these pacing modalities taking into account procedural complication rates and fluoroscopy times. Conflict of interest: none declared. References 1. Abraham WT, Hayes DL. Cardiac resynchronization therapy for heart failure. Circulation 2003;108: Bleeker GB, Bax JJ, Fung JW, van der Wall EE, Zhang Q, Schalij MJ et al. Clinical versus echocardiographic parameters to assess response to cardiac resynchronization therapy. 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