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Cardiac resynchronization therapy and conduction system pacing in heart failure: System implantation and programming

Cardiac resynchronization therapy and conduction system pacing in heart failure: System implantation and programming
Literature review current through: Jan 2024.
This topic last updated: Sep 26, 2023.

INTRODUCTION — Cardiac physiologic pacing (CPP) is defined here as any form of cardiac pacing intended to restore or preserve synchrony of ventricular contraction and includes both conventional cardiac resynchronization therapy (CRT) and the more recently adopted conduction system pacing (CSP). CRT is an established treatment for select patients with chronic heart failure (HF) with both reduced ejection fraction and bundle branch block [1-4]. The traditional definition of CRT involves biventricular or left ventricular (LV)-only pacing. However, His bundle pacing (HBP) and left bundle area pacing (LBAP) can also prevent or mitigate ventricular dyssynchrony that is associated with an underlying bundle branch block or that is created by myocardial ventricular pacing and are broadly referred to as conduction system pacing (CSP) [5,6]. CRT can be achieved with a device designed only for pacing (CRT-P) or with the added capability of defibrillation (CRT-D) (image 1).

This topic will review implantation techniques for CRT, LBAP, and HBP systems, as well as the approach to programming.

The rationale and indications for CRT in patients with HF are discussed separately. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system", section on 'Rationale for CRT' and "Cardiac resynchronization therapy in heart failure: Indications and choice of system" and "Cardiac resynchronization therapy in atrial fibrillation".)

TRADITIONAL CRT WITH A CORONARY SINUS LEAD

System overview — Most cardiac resynchronization therapy (CRT) implantations are performed via a transvenous approach with placement of a right atrial (RA) lead, right ventricular (RV) lead, and LV lead (image 1).

Right atrial lead An atrial lead allows sensing and tracking of the atrial rhythm (either intrinsic or paced atrial rhythm) to appropriately time ventricular activation (ie, allow for atrial contraction before ventricular activation). The RA lead provides atrial pacing as needed.

In patients with indications for CRT and cardioverter-defibrillator function but who do not require atrial pacing, there are defibrillation leads with floating atrial electrodes with sensing-only function. Devices that use this type of lead are programmed to the VDD pacing mode.

Patients with atrial fibrillation or flutter who have indications for CRT may not require an atrial lead; the absence of functional atrial contraction obviates the need for pacing. The details on CRT in patients with atrial fibrillation are discussed separately. (See "Cardiac resynchronization therapy in atrial fibrillation".)

Right ventricular lead The RV lead is an essential component for biventricular pacing systems; its role is to sense the intrinsic ventricular rhythm, pace the RV, and provide tachyarrhythmia therapy in devices capable of such therapy. The optimal programming of the RV lead is described elsewhere in this topic. (See 'Approach to programming' below.)

Most RV leads are placed transvenously. The RV lead tip is usually placed in the septum; greater separation from the LV lead improves the ability to synchronize the ventricles [7]; in the case of CRT with defibrillation (CRT-D), this position also provides an optimal shocking vector.

Epicardial placement via a direct surgical approach is another option for RV lead placement; this method of placement is reserved for patients who cannot undergo transvenous placement (eg, due to venous thrombosis) or who require concomitant cardiac surgery (eg, coronary artery bypass grafting). Further details on epicardial lead placement are discussed elsewhere in this topic. (See 'Surgical placement of an epicardial lead' below.)

Left ventricular lead In most patients, the cause of dyssynchrony is electrical delay or block in the left-sided His-Purkinje conduction system. Placement of an LV lead via the coronary sinus allows for pacing of the LV, which can restore electrical and mechanical synchrony of ventricular contractions (image 1).

Pulse generator The pulse generator connects to the leads to provide pacing stimuli and regulation of the rhythm according to a number of settings and algorithms. The pulse generator contains the battery and the interface for programming changes and is typically placed in the region medial to the deltopectoral groove.

Procedure for placement — During the placement of a traditional CRT system, the steps include:

Appropriate sedation is established. (See "Anesthetic considerations for electrophysiology procedures", section on 'Procedures for cardiac implantable electronic devices'.)

Standard central venous access is obtained for each lead to be implanted. Ipsilateral upper extremity contrast venography of the central venous system is often used for guidance.

A pocket for the device is surgically created within the plane of the prepectoral fascia below the clavicle. Venous access is obtained from the pocket to the axillary, subclavian, or cephalic vein, and the leads are extended to the RA and RV. Once in place, the leads are anchored to the pectoral muscle.

The LV lead is placed similarly to the RA and RV leads but is placed in the coronary sinus instead of within a cardiac chamber. The placement of the LV lead is typically the most complicated aspect of CRT implantation. The placement of the LV lead consists of the following:

Contrast injections through the guide sheath, fluoroscopic landmarks, or electrophysiologic signals are used to identify the ostium of the coronary sinus. The operator may also identify anatomy such as abnormal position of the coronary sinus ostium, presence of venous valves (eg, Thebesian valve, Valve of Vieussens), or coronary sinus strictures [8].

The coronary ostium is then accessed with a wire or catheter and the coronary sinus guide sheath is advanced into the coronary sinus. The lead is advanced through the sheath into one of the venous branches for LV pacing based on criteria.

Further details on optimal coronary sinus lead placement are discussed elsewhere in this topic. (See 'Coronary sinus lead positioning' below.)

The success of de novo CRT system placement is high and associated with the experience of the implanting center. In approximately 5 to 10 percent of implantation attempts, the LV lead cannot be placed.

In a study of de novo transvenous CRT implants among 2014 patients from 114 centers, the overall success rate was 97.1 percent, median fluoroscopic time was 17 minutes, median dye use was 25 mL, and adverse events occurred in 2.6 percent [9].

In an analysis of the National Inpatient Sample Database involving 410,104 de novo CRT implants between 2003 and 2011, lower hospital volume was associated with higher rates of in-hospital mortality [10].

Placement issues with preexisting pacing systems — For patients with a preexisting transvenous pacing or defibrillation system, most patients can undergo addition of a coronary sinus lead by opening the existing pocket, adding a coronary sinus lead, and upgrading the pacing generator as appropriate. However, patients who require addition of a coronary sinus lead (ie, device "upgrade") are more likely to have venous obstruction (prevalence 10 to 30 percent) caused by the existing system that may prevent placement of a coronary sinus lead (10 to 30 percent) [11-15].

In patients undergoing device upgrade, regardless of the absence of symptoms suggesting venous stenosis (eg, arm edema), we routinely obtain contrast venography prior to CRT upgrade to aid in procedural planning and execution [14,16].

If contrast venography suggests that typical left-sided transvenous coronary sinus lead placement is not feasible, the following strategies may be used to place a coronary sinus lead. The approach to such patients depends on local experience with treatment of the obstruction and the risks of alternative placement strategies:

Lead extraction and coronary sinus lead placement – One common approach is transvenous lead extraction, which can restore venous access, followed by transvenous coronary sinus lead placement and replacement of the extracted lead [17]. (See "Cardiac implantable electronic device lead removal".)

In the LEXICON study of 2405 extracted leads, this approach was associated with clinically successful lead extraction in 97.7 percent, a major adverse event rate of 1.4 percent, and procedural death in 0.28 percent [18]. Risk factors for complications include body mass index <25 kg/m2 and procedures performed at low volume extraction centers.

Treatment of venous obstruction prior to lead placement – Treatment of venous obstruction with percutaneous venoplasty prior to lead implantation may allow for successful CRT upgrade [12].

Venous cannulation beyond the obstruction – This approach requires "deep" transvenous access proximal to the point of obstruction in a more central or medial point. The risks of this approach include vascular or thoracic trauma, pneumothorax, and increased risk of lead fracture on follow-up [19,20].

A related strategy is parasternal or paraclavicular lead tunneling to an alternate point of ipsilateral venous entry. In this strategy, the ipsilateral internal jugular vein serves as the point of entry. Concerns include risk for skin erosion over bony sternal or clavicular prominences where there is typically minimal subcutaneous tissue, which may lead to subsequent transvenous extraction. For these reasons, this approach is rarely utilized.

Surgical placement of an epicardial LV lead – Surgical placement of an epicardial LV pacing lead is discussed elsewhere in this topic. (See 'Surgical placement of an epicardial lead' below.)

Contralateral implant of a coronary sinus lead or de novo system – If upgrade of a left- or right-sided system is not feasible, a new system can be placed on the contralateral side with full or partial abandonment of the preexisting system. To minimize the number of new leads when using the contralateral side, a lone coronary sinus lead can be implanted on the contralateral side and tunneled subcutaneously across the chest to connect to the preexisting device pocket. Disadvantages of abandoned leads include increased risks of venous occlusive disease (eg, superior vena cava stenosis), device-device or lead-lead interactions, and bloodstream infection [21].

In aggregate, the ability to safely place a coronary sinus lead in patients with preexisting transvenous cardiac implantable electronic device systems at experienced centers is high:

In a contemporary comparative study of 1496 patients at a high-volume tertiary center who were undergoing de novo or upgrade CRT procedures, the rates of procedural success were similar (97 versus 96 percent), as were the rates of complications at 90 days (5.1 versus 4.6 percent) [16].

In an analysis comparing 19,546 CRT upgrades with 464,246 de novo procedures in the United States between 2003 and 2013, the upgrades were independently associated with increased mortality (odds ratio [OR] 1.91), cardiac perforation (OR 3.2), and need for lead revision (OR 2.09) [22].

In the REPLACE registry, the complication rates for procedures involving lead additions, particularly an LV lead, were greater than those for generator replacement alone [23].

Coronary sinus lead positioning

General principles — The optimal LV lead location is that at which the lead effectively paces the site of greatest electromechanical delay while avoiding phrenic nerve stimulation. However, the patient’s coronary sinus and LV venous anatomy (image 2) determine where the LV lead can be placed. The most common LV venous anatomy is composed of an anterior vein coursing in the interventricular groove, an anterolateral branch coursing diagonally from the LV base to the apex of the LV, a midlateral and/or posterolateral vein that often shares a common trunk, and the middle cardiac vein coursing posteriorly to the LV apex.

The available evidence suggests that the optimal position for the LV lead is generally the lateral or posterolateral wall (image 2). In the presence of left bundle branch block (LBBB), the basal posterolateral wall is often the last segment to contract in a dyssynchronous LV. In the follow-up results of the MADIT CRT study, only patients with lateral and posterior LV lead locations derived long-term mortality benefit from CRT over implantable cardioverter-defibrillator (ICD) alone [24]. Additionally, a more basal pacing site has also been associated with better rates of CRT response.

Strategies for optimal lead placement — In general, the usual strategy for initial LV placement is guided by anatomy; the lead tip is positioned near the basal position of the lateral wall at a stable site with acceptable pacing parameters and where there is no left phrenic nerve capture. Some implanting clinicians also use electrical or mechanical information including the Q-LV interval (figure 1) to further direct lead placement and the optimal pacing site.

Site of greatest electrical delay – In patients with LBBB, we often target the site of greatest LV electrical delay for pacing stimulation (figure 1). In patients without LBBB, we do not select the pacing site using the Q-LV interval [25].

The following studies illustrate the importance of LV electrical delay as measured by Q-LV as a predictor of improvement in hemodynamic improvement:

In a prospective acute hemodynamic studies of 31 and 32 patients undergoing CRT implant, Q-LV was strongly associated with hemodynamic improvement as measured by dP/dt max independent of the pacing mode [26,27].

In a prospective study of 156 patients, Q-LV was the only independent predictor of improvement in LV ejection fraction (LVEF) and decrease in LV end-systolic volume in follow-up [28].

In an analysis of the SMART AV trial involving 426 patients, Q-LV was associated with greater improvement in mitral regurgitation, suggesting an additional physiologic mechanism for targeting the site of greatest electrical delay [29].

Other methods of pacing site selection – Other methods of pacing site selection may play a role but are used less frequently:

Right to left electrical delay – The presence of LBBB causes overall delayed LV activation compared with the RV, leading some operators to measure the interlead electrical delay (IED) time, which is the time between sensing of the native impulse at the RV and sensing of the native impulse at the LV lead. In a study of 68 patients, IED was independently associated with CRT response (reverse remodeling), even when accounting for the presence of myocardial scar (OR 3.99, 95% CI 1.02-15.7) [30]. In another study involving 160 patients, an IED ≥100 ms was associated with more pronounced LV reverse remodeling when lead implantation site was guided by identification of the latest mechanical delay in a nonscarred myocardial segment [31].

Site of greatest mechanical delay – After optimizing the site of pacing using the site of greatest electrical delay, some experts evaluate for the site of greatest mechanical delay. Targeting the site of greatest mechanical delay for pacing stimulation has been associated with improved CRT outcomes in some studies:

-Echocardiographic-based imaging and magnetic resonance imaging have been utilized to evaluate the value of LV pacing at or near the area of greatest mechanical delay [32-34].

-Tissue Doppler imaging has been the most widely studied and utilized method in clinical practice [35-42]. Tissue Doppler imaging was initially assessed in a series of 54 patients, and a greater reduction in end-systolic volume was associated with LV pacing at the site of greatest mechanical delay [43].

-An additional echocardiographic-based method is myocardial strain imaging [44,45]. (See "Tissue Doppler echocardiography", section on 'Use in heart failure and resynchronization therapy'.)

Although direct measures of mechanical dyssynchrony have been investigated as a means of identifying responders to CRT [46-50], the clinical utility of such assessment has not been established.

Avoiding LV scar – The optimal position for the LV lead is in the vicinity of viable myocardium that is not in or immediately adjacent to scar tissue. Pacing in regions of LV scar has been associated with lower response rates. In addition, pacing in a densely scarred region may require higher pacing outputs, which can lead to premature battery drain. The burden of scar may influence the efficacy of CRT pacing [32,51-53].

Placement of a quadripolar lead – We typically place a quadripolar LV pacing lead. These leads reduce the incidence of phrenic nerve stimulation and improve the likelihood of CRT response by providing an array of options for the site of pacing [54]. Selecting the site for optimal pacing and algorithms that make use of multiple coronary sinus pacing sites are discussed elsewhere in this topic. (See 'Other parameters for optimization' below.)

Approach to programming

Initial settings — In general, we optimize device settings for the best clinical response and lowest battery use. The optimal device settings at the time of implant are not clearly defined and may be patient specific. The following principles influence our choice of initial programming:

Program the atrioventricular delay to optimize resynchronization – For patients who are in sinus rhythm, the pacing mode is typically programmed DDD, DDDR, or VDD depending on the need for atrial pacing. For patients in sinus rhythm and with intact atrioventricular (AV) conduction, the AV delay should be set to a value that minimizes the QRS duration.

Increase the frequency of pacing – In patients with continuous atrial fibrillation and a relatively high resting ventricular rate, we increase the lower rate limit to target 100 percent CRT pacing.

Choose the optimal site of pacing – We pace the LV at a site with the greatest electrical delay (measured by the Q-LV interval) (figure 1) that does not result in a wider QRS morphology, LBBB morphology, or apical QRS morphology. The site of pacing should not stimulate the phrenic nerve.

Minimize power consumption – We program CRT devices to promote battery longevity by choosing pacing sites with the lowest possible electrical thresholds, lowest impedance measurements, and shortest pulse width. Minimizing RV pacing stimulation with fusion pacing can extend battery longevity.

Ancillary settings – Other pacing settings are available, but routine selection of one method over another is controversial. (See 'Other parameters for optimization' below.)

Identification of and approach to nonresponders — Most experts define nonresponse to CRT as lack of improvement in LVEF or New York Heart Association (NYHA) class. However, other criteria that can be used to identify nonresponders include other measures of LV function (eg, global longitudinal strain), LV dimensions, exercise capacity and functional status, and quality of life [55].

For most patients with HF with reduced ejection fraction who do not initially respond to CRT, we evaluate for clinical causes of nonresponse (eg, progressive HF, nonadherence to medical therapy) and adjust therapies as needed. In most patients, the initial approach to nonresponse is to change pacing parameters based on the surface electrocardiogram (ECG). Pacing vectors (ie, sites) are adjusted until the narrowest QRS duration is achieved and there are no signs of an apical pacing morphology (ie, LBBB appearance in V1 with a superior axis that is negative in limbs leads II, III, and aVF with a widened QRS >200 ms).

However, optimizing pacing with electrophysiologic parameters does not always translate to a clinical response or improved mechanical synchrony. For example, ventricular scar patterns can create "balanced delay" in which the overall right and left ventricular activations are relatively simultaneous (ie, paced QRS appears narrow) but remain mechanically dyssynchronous due to nonhomogenous conduction through and around intrinsic LV scar.

Mismatch between the surrogates for mechanical synchronization (eg, surface ECG parameters) and true mechanical resynchronization likely explain the discrepancy:

In patients with little or no intrinsic AV conduction (ie, complete heart block), achieving a more narrowly paced QRS duration was associated with reduction of LV end-systolic volume of ≥15 percent from baseline [56].

In a substudy of the PROSPECT trial, greater shortening of the paced QRS over the intrinsic QRS duration was also associated with significantly increased likelihood of clinical and echocardiographic response (OR 0.89) [57].

In an analysis of the MADIT CRT trial, shortened paced QRS duration was not associated with better outcomes, while apical pacing demonstrated worse outcomes [58].

Other parameters for optimization — Options for programming that are used in specific scenarios include:

Fusion pacing – In patients with intact AV conduction and LBBB, fusion pacing can be used rather than standard biventricular pacing. Fusion pacing entails timing LV pacing to coincide with normal RV activation (figure 2). This is referred to as adaptive CRT. The timing of LV pacing is determined from the sensed time between RA depolarization and RV activation [59]. Thus, fusion-pacing algorithms commonly result in a more narrowly paced QRS than either traditional biventricular pacing or LV-only pacing; the intact right bundle and/or septal His-Purkinje allows more rapid electrical depolarization. A similar algorithm allows for dynamic adjustment of the AV delay to accommodate ventricular remodeling while allowing the option of using varying combinations of LV pacing, RV pacing, and intrinsic conduction (ie, so-called "triple fusion") [60,61]. Fusion pacing is not the same as "LV-only" CRT pacing; the latter ignores RA-RV conduction.

In patients with high RV pacing thresholds whose device is capable of fusion pacing, fusion pacing can improve battery longevity and may complement other programming changes directed at preserving battery life.

The evidence on fusion pacing includes two trials that arrived at different conclusions regarding its effect on clinical outcomes, though the larger trial had longer follow-up and showed no clear effect on clinical outcomes:

In a trial (AdaptResponse) that enrolled 3617 patients with an LVEF ≤35 percent, NYHA class II to IV symptoms, and LBBB (QRS ≥140 ms in males and ≥130 ms in females), the rates of all cause death or intervention for HF decompensation (ie, primary composite endpoint) were similar in patients assigned to adaptive CRT or to conventional CRT after eight years of observation (23.5 versus 25.5 percent; hazard ratio [HR] 0.89, 95% CI 0.78-1.01) [62]. In a subgroup analysis, patients assigned to adaptive CRT programming were less likely to undergo generator exchange for battery depletion (24 versus 15 percent; HR 0.59, 95% CI 0.47–0.75).

In the Adaptive CRT trial, 478 patients were randomized in a 2:1 ratio to fusion pacing (LV pacing synchronized to RV contraction using a proprietary algorithm) versus standard CRT with echocardiographic-guided optimization [60]. At a mean of 20 months of follow-up, the fusion pacing group demonstrated a lower likelihood of all-cause hospitalizations (OR 0.54, 95% CI 0.31-0.94). The effects of programming on battery life were not reported.

Multisite pacing – In patients with a quadripolar lead, some experts use the multisite pacing programming (MPP) algorithm. This is typically done at the time of implant. MPP is a proprietary algorithm that simultaneously uses two or more LV pacing configurations to overcome transmyocardial conduction delay or improve intraventricular dyssynchrony.

In an observational study of 110 patients comparing standard with multisite pacing, the one-year echocardiographic response rate with optimally positioned leads was 72 percent with standard programming and 90 percent with MPP [61].

In a meta-analysis of studies comparing MPP with conventional CRT, the use of MPP was associated with decreased HF hospitalizations, improved LVEF, increased CRT response, and decreased all-cause mortality [63]. However, the data from randomized controlled trials are less compelling, and multisite pacing increases the rate of battery depletion.

LV-only pacing – LV-only pacing is infrequently used in modern practice. Randomized trials that compared LV-only pacing with standard LV pacing (PATH-CHF, DECREASE-HF, B-LEFT HF, GREATER EARTH) showed no advantage of LV-only pacing in patients with LBBB [64-67].

Echocardiographic optimization – We do not routinely perform echocardiographic optimization of CRT pacing. There is limited evidence to support routine optimization of CRT pacing with echocardiographic parameters. The approaches to echocardiographic optimization include:

AV optimization – For CRT pacing, a shortened AV delay (ie, 90 to 120 ms) reduces the likelihood of native AV conduction and increases the percentage of biventricular pacing. In patients who fail to experience improvement in symptoms or cardiac function following CRT implantation, postprocedural adjustment in the AV delay ("AV optimization") with Doppler echocardiographic assessment may be helpful in highly selected individuals.

The typical strategy is to program the AV delay such that the end of atrial contraction (marked by the end of the A wave) is timed to coincide with the onset of ventricular contraction (marked by the onset of systolic mitral regurgitant flow) [68]. However, the clinical efficacy of AV optimization has not been established, as randomized clinical trials have failed to demonstrate benefit [69]. In a post hoc analysis of the MADIT CRT study involving 1235 patients, sensed AV delays less than 120 ms demonstrated overall better clinical outcomes when compared with longer sensed AV delays, likely attributable to a greater percentage of biventricular pacing in place of intrinsic activation via the native diseased His-Purkinje system [70].

VV optimization – With CRT devices, the timing between the right and left ventricular pacing stimulus (VV timing) can be adjusted, but the optimal programming strategies for VV timing have not been fully defined and may be patient specific. There is limited evidence to support routine adjustment of VV timing using echocardiographic parameters.

Complications — The complications of CRT pacing include coronary sinus or coronary vein trauma, pneumothorax, pocket hematoma, infection, and phrenic nerve pacing [71-74]. There are also specific concerns with LV lead placement, such as prolonged radiation exposure due to long procedure times in challenging cases [75].

Postoperative – CRT implantation complication rates varied among studies but appear to be higher with CRT upgrades [22] and lower among high-volume centers [10]:

In a study of 2014 patients from 114 centers undergoing de novo transvenous CRT implant, the composite complication rate was 2.6 percent at three months, most commonly involving LV lead dislodgement in 1.7 percent of patients and phrenic nerve stimulation not amenable to reprogramming in 0.5 percent of patients [9].

A meta-analysis of clinical trials, albeit among older studies, reported an overall acute complication rate of 14 percent that is largely driven by lead-related complications but also includes 0.8 percent perioperative mortality [76].

With regard to CRT upgrades, one study found an acute complication rate of 11 percent [77].

The REPLACE Registry was a larger multicenter study of 1700 patients [23]. The major complication rate was 4 percent for isolated generator change, 15 percent for addition or revision of a lead along with generator change, and 19 percent if the lead revised was the LV lead.

Higher in-hospital mortality rates were observed in a cohort of 26,887 patients undergoing ICD and/or CRT implantation that included older adults with rates ranging from 0.7 to 1.2 to 2.2 percent in patients aged <80, 80 to 85, and >85 years [78]. While patients over 80 years old undergoing CRT implantation may face higher complication rates than younger patients, longer-term data suggest that mortality rates for these patients are only slightly higher than in the general octogenarian population.

Long-term – The long-term complications of CRT include device malfunction and infection. The incidence of late complications is illustrated by the following results from a review of implantation success rates and safety outcomes in studies of patients undergoing CRT or CRT-D implantation [73]:

In 54 studies (6123 patients) of CRT-alone devices, 5 percent of CRT devices malfunctioned, and 2 percent of patients were hospitalized for infections in the implant site over six months of follow-up. During a median follow-up of 11 months, lead problems occurred in 7 percent of CRT devices.

While there is a theoretical risk that pacing from an LV lead may be proarrhythmic due to alterations in depolarization and repolarization sequences (eg, "dispersion of refractoriness"), a pooled analysis from 14 randomized controlled trials did not demonstrate any excess risk of sudden death or noncardiac death in CRT device recipients, on average [79]. However, there are cases of individual patients who experience ventricular tachycardia storm after CRT is activated.

In 36 studies (5199 patients) of combined CRT-D devices, 5 percent of CRT-D devices malfunctioned, 1 percent of patients developed site infection, and lead problems were detected in 7 percent of patients over 12 months of follow-up.

SURGICAL PLACEMENT OF AN EPICARDIAL LEAD

System overview — Epicardial cardiac resynchronization therapy (CRT) systems involve placement of a pacing lead directly on the lateral LV epicardium via a thoracotomy or thorascopically. The RA and RV leads are usually transvenous, but in some patients are also placed epicardially. These leads are connected to a pulse generator that provides pulse stimuli and programming.

Epicardial lead placement is reserved for patients in whom a coronary sinus lead cannot be placed (eg, venous occlusive disease, anatomy incompatible with coronary sinus lead placement). In rare cases, patients with an indication for CRT may undergo surgical lead placement at the time of concomitant cardiac surgery (eg, valve surgery, coronary artery bypass grafting).

Additional details on the indications for epicardial lead placement are discussed separately. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system", section on 'Alternative approaches'.)

Procedure and lead placement — The technique for surgical LV lead placement includes a mini-thoracotomy approach in the fourth or fifth intercostal space anterior to the midaxillary line. Typically, single lung ventilation is performed to allow dissection into the pericardial space for implantation of the epicardial LV lead [80]. It is important that the lead be placed at a basal lateral location. The lead is fixed directly to the cardiac tissue using a specifically designed instrument and tested in the same manner as leads placed via a transvenous approach. A key advantage of surgical epicardial lead placement is that lead placement is not confined to the anatomic branches of the LV venous circulation as is the case with transvenous placement. (See 'General principles' above.)

Programming — In nearly all cases, the programming of epicardial CRT systems is the same as coronary sinus systems. (See 'Approach to programming' above.)

Complications — Epicardial lead placement entails an increased risk of adverse events and provides no greater benefit compared with transvenous placement. The risk of surgical lead placement is variable; some centers report complication rates similar to transvenous lead placement, while others report a much higher mortality rate than expected with transvenous lead placement:

In a study of 30 patients who underwent cardiac surgery for isolated LV lead placement via a mini-thoracotomy following failed transvenous placement, the epicardial lead placement was successful in all patients and perioperative mortality was zero. However, this study did not report electrical lead testing data, rate of bleeding, or infectious complication rate [81].

In a series of 42 patients with "stand-alone" LV epicardial lead placement using a mini-thoracotomy approach, the mean length of stay was 3.4 days, and the 30-day adverse event rate was 17.5 percent; the adverse events included 4.8 percent mortality, 7.5 percent LV lead noncapture, and 5 percent infection [82].

A five-year study compared 895 patients who received a transvenous coronary sinus lead with 158 patients who received an epicardial LV lead and found a lead revision was performed in only 2 percent of patients with an epicardial lead compared with 10 percent of patients with a transvenous lead [83]. However, the threshold to revise an epicardial lead is likely higher compared to a transvenous lead.

A study that compared patients with surgically placed epicardial LV leads with transvenously placed leads found no difference over a mean five years of follow-up in which the overall clinical response rate to CRT pacing was 65 percent [84]. In this study, major adverse events occurred in 5 percent of patients undergoing stand-alone LV lead placement and 14 percent of patients with concomitant LV lead placement.

HIS BUNDLE PACING

Components of His bundle pacing systems — The goal of His bundle pacing is to capture the His-Purkinje system to improve ventricular synchrony. His bundle pacing (HBP) either "directly" (ie, selectively) stimulates the His-Purkinje system or results in para-Hisian (ie, nonselective) stimulation that captures both the His-Purkinje system and adjacent RV myocardium [85]. The use of His bundle pacing in patients in who cannot undergo coronary sinus lead placement is discussed separately. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system", section on 'Alternative approaches'.)

In a HBP system, the RV lead is placed directly into the proximal septum at the location of the bundle of His. If indicated, an RA lead is placed in a manner similar to coronary sinus systems. (See 'System overview' above.)

Lead placement — His bundle leads are placed in the septum and are guided by pacing maneuvers to confirm His capture. After establishing sedation and transvenous access similar to coronary sinus leads, placement of a His bundle lead consists of the following:

A pacing lead is advanced through a delivery system to a site on the atrial side of the tricuspid valve annulus or beyond the annulus in the anteroseptal RV.

Next, the His bundle pacing site is evaluated using electrograms recorded from the candidate lead and the ECG that results from pacing [5,86]. Published criteria suggest that the His Bundle pacing should result in a QRS duration less than ≤120 ms and ideally include a 20 to 40 ms isoelectric segment between the pacing stimulus and the QRS complex. Variants of this HBP technique include the use of a diagnostic electrophysiology catheter as a fluoroscopic reference, injection of intravenous contrast, or the use of an electroanatomic mapping system [86].

Placement of a His pacing system is successful in approximately 50 to 80 percent of attempts, though experience with this approach continues to develop:

In a meta-analysis of retrospective studies, HBP for conduction system pacing (CSP) had an average implant success rate of 80 percent and was associated with mean paced QRS duration 122.9±12.0 ms [5]. Compared with baseline values, there were improvements in LVEF, LV volumes, and HF symptoms. The most common complication was an increase in capture thresholds during follow-up.

In the His-SYNC pilot trial that included 41 patients with HF and left bundle branch block (LBBB), patients assigned to HBP and biventricular cardiac resynchronization therapy (CRT; ie, CRT with a coronary sinus lead) had similar New York Heart Association class and Kansas City Cardiomyopathy Questionnaire scores during follow-up [87]. However, many patients (48 percent) randomized to HBP crossed over to biventricular CRT due to inability to correct the native LBBB with HBP, and many patients (26 percent) randomized to biventricular CRT crossed over to HBP due to anatomic difficulties, which limits the external validity of the results.

Programming — Programming is guided by the underlying indication for the pacemaker. During evaluation and programming, it is important to distinguish between septal capture, nonselective His capture, and His bundle capture during threshold testing. However, studies have shown that programming the pacemaker outputs to achieve selective His bundle capture does not provide better outcomes compared with nonselective capture [88].

Complications — Uncommon but unique complications of HBP include atrial oversensing and high pacing thresholds [89,90]. There are limited data that compare complications among patients undergoing cardiac physiologic pacing (CPP).

Atrial oversensing

High pacing thresholds

LEFT BUNDLE AREA PACING

Components of left bundle area pacing systems — The goal of left bundle area pacing (LBAP) is to provide conduction system pacing (CSP) by stimulating the native cardiac conduction system to partially overcome intrinsic bundle branch block or interventricular conduction delay. The indications for LBAP pacing systems are discussed separately. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system", section on 'Choice of CRT system'.)

LBAP systems are composed of an RV lead that paces in the area of the left bundle and, if indicated, a standard RA lead.

Lead placement — LBAP leads are placed deeply in the proximal RV septum and are tested to confirm left bundle branch capture. Left bundle lead placement also requires 12-lead procedural ECG recording and a delivery sheath or catheter and should only be implanted by experienced operators and in accordance with published techniques, criteria, and applicable equipment [91].

The delivery system is first advanced into the RV over a guidewire. A transvenous pacing lead with either an extendable-retractable or fixed screw is then advanced through the delivery system to the appropriate location on the RV septum.

The candidate location is selected beginning approximately 1 to 1.5 cm distal (apical) and inferior of the location of the His bundle.

Unipolar pacing from the initial candidate endocardial location allows recording of the baseline impedance, 12-lead ECG of the paced QRS morphology, and LV activation time (LVAT) as measured from the pacing stimulus to the peak depolarization in leads V5 to V6. Initial pacing prior to screw fixation is expected to yield an overall left bundle branch block (LBBB)-pattern QRS complex with characteristic "w" pattern in lead V1.

The lead is then advanced into the septum with periodic pacing to evaluate for an ECG morphology consistent with left bundle capture. Contrast venography, unipolar ring pacing, and impedance measurements can help identify the depth in the septum and whether the lead has penetrated into the LV cavity (image 3).

The final location is accepted in accordance with published standards, but generally includes evidence of left bundle capture as assessed by a relatively narrow QRS duration and RBBB or rsr’ morphology in V1, and LVAT ≤80 ms in V5 or V6.

In a prospective study of 63 patients with HF and complete LBBB, CSP was successfully achieved in 97 percent with LBAP, resulting in QRS narrowing to mean 118±12 ms associated with improvements in LVEF, volumes, and HF symptoms. Normalization of LVEF ≥50 percent occurred in 75 percent of patients [6].

Programming — Programming is guided by the underlying indication for the pacemaker. During evaluation and programming, it is important to distinguish between septal capture and left bundle capture [92].

Complications — The complications of LBAP leads are similar to those of His bundle pacing (HBP) leads (see 'Complications' above), but LBAP usually has better pacing thresholds and lower risk of atrial oversensing.

Because LBAP pacing leads are placed more distally and deeper in the septum, the risks of septal perforation are higher than those observed with HBP leads [93].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Cardiac implantable electronic devices".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Cardiac resynchronization therapy (The Basics)")

SUMMARY AND RECOMMENDATIONS

Types of cardiac physiologic pacing:

Definitions – Cardiac physiologic pacing (CPP) is defined as any form of cardiac pacing intended to restore or preserve synchrony of ventricular contraction. CPP can be achieved with cardiac resynchronization therapy (CRT) or by engaging the intrinsic conduction system via conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBAP). CRT is most commonly achieved by biventricular pacing using a coronary sinus branch or epicardial left ventricular (LV) pacing lead.

Traditional resynchronization systems with a coronary sinus lead – Most cardiac resynchronization therapy (CRT) implantations are performed via a transvenous approach in which leads are placed in the right atrium (RA), right ventricle (RV), and coronary sinus (ie, left ventricular [LV] pacing lead) (image 1). (See 'Traditional crt with a coronary sinus lead' above.)

The coronary sinus lead is typically placed at the site of greatest electromechanical delay while avoiding phrenic nerve stimulation. (See 'General principles' above.)

Surgical placement of an epicardial lead – Epicardial CRT systems are composed of transvenous leads in the RA and RV and a lead placed directly on the lateral LV epicardium via a thoracotomy. (See 'Surgical placement of an epicardial lead' above.)

The indications for epicardial lead placement are discussed elsewhere. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system", section on 'Alternative approaches'.)

His bundle pacing – The goal of HBP is to enable pacing and capture of the His-Purkinje system, which can improve synchrony and ventricular activation. His bundle leads are placed in the septum and are guided by pacing maneuvers to confirm His capture. (See 'Components of His bundle pacing systems' above.)

The use of HBP in patients in whom a coronary sinus lead cannot be placed is discussed separately. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system", section on 'Alternative approaches'.)

Left bundle area pacing – The goal of left bundle area pacing (LBAP) is to provide CSP by stimulating the native cardiac conduction system to partially overcome intrinsic bundle branch block or interventricular conduction delay. LBAP systems are composed of an RV lead that paces in the area of the left bundle and, if indicated, a standard RA lead. (See 'Components of left bundle area pacing systems' above.)

The indications for LBAP pacing systems are discussed separately. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system", section on 'Choice of CRT system'.)

Initial program settings – In general, we optimize device settings for the best clinical response and lowest battery use. The optimal program settings at the time of implant have not been fully defined and may be patient specific. Initial programming includes (see 'Initial settings' above):

Program the atrioventricular delay to optimize resynchronization – For patients who are in sinus rhythm, the pacing mode is typically programmed DDD, DDDR, or VDD depending on the need for atrial pacing. For patients in sinus rhythm and with intact atrioventricular (AV) conduction, the AV delay should be set to a value that minimizes the QRS duration.

During implantation and follow-up of patients with CPP devices, it is essential to electrocardiographically demonstrate biventricular (for CRT) or conduction system (for CSP) capture.

Increase the frequency of pacing – In patients with relatively high resting heart rate or continuous atrial fibrillation, we increase the lower rate limit to target 100 percent CRT pacing.

Choose the optimal site of coronary sinus lead pacing – We pace the LV at a site with the greatest electrical delay (measured by the Q-LV interval) (figure 1) that does not result in a wider QRS morphology, left bundle branch block (LBBB) morphology, or apical QRS morphology. The site of pacing should not stimulate the phrenic nerve.

Minimize power consumption – We program CPP devices to promote battery longevity by choosing pacing sites with the lowest possible electrical thresholds, lowest impedance measurements, and shortest pulse width.

Ancillary settings – Other pacing settings are available, but routine selection of one method over another is controversial. (See 'Other parameters for optimization' above.)

CRT nonresponse – Most experts define nonresponse to CRT as lack of improvement in LV ejection fraction (LVEF) or New York Heart Association (NYHA) class. (See 'Identification of and approach to nonresponders' above.)

Initial approach to nonresponders – For most patients with HF with reduced ejection fraction who do not initially respond to CRT, we evaluate for causes of nonresponse and adjust settings as appropriate. In most patients, the initial approach to nonresponse is to change pacing parameters based on the surface ECG. (See 'Identification of and approach to nonresponders' above.)

Additional programming – If a response to CRT is not achieved with optimization of the surface ECG, other parameters may be adjusted on an individual basis (eg, fusion pacing, multisite pacing, echocardiographic optimization). (See 'Other parameters for optimization' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Leslie A Saxon, MD, Teresa DeMarco, MD, Wilson Colucci, MD, and Daniel J Cantillon, MD, FACC, HRS, who contributed to earlier versions of this topic review.

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Topic 3500 Version 34.0

References

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