Cardiac resynchronization therapy in systolic heart failure: Indications and choice of system

INTRODUCTION — 

In patients with left ventricular (LV) systolic dysfunction and ventricular dyssynchrony, the mechanics of systole may be improved by resynchronizing LV electromechanical activation. Cardiac resynchronization therapy (CRT) is a modality of cardiac pacing that provides simultaneous or nearly simultaneous electrical activation of the LV and right ventricle (RV) via stimulation of the LV and RV (biventricular pacing) or LV alone. CRT devices pace the LV via a lead placed in a branch of the coronary sinus or, less commonly, via either an epicardial LV lead or a right-sided lead placed near or in the left bundle branch block or His bundle. This last form of cardiac resynchronization using an RV lead is commonly referred to as conduction system pacing. (See "Cardiac resynchronization therapy and conduction system pacing in heart failure: System implantation and programming".)

Many of the indications for CRT overlap with those for implantable cardioverter-defibrillators (ICDs). The indications and evidence for ICD use are discussed separately. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)

CRT is a key component of the management of patients with heart failure (HF) with reduced ejection fraction in addition to pharmacologic therapy and other device-based therapies, as discussed separately. (See "Overview of the management of heart failure with reduced ejection fraction in adults".)

Details on different forms of CRT pacing and optimal placement and programming of CRT systems are discussed separately. (See "Cardiac resynchronization therapy and conduction system pacing in heart failure: System implantation and programming".)

EFFECTS OF DYSSYNCHRONY AND RESYNCHRONIZATION — 

In the cardiomyopathic state, dyssynchrony leads to inefficient LV contraction that may reduce cardiac output, exacerbate functional mitral regurgitation, and worsen adverse LV remodeling (eg, dilation) [1]. Dyssynchrony refers to both dyssynchronous contraction within the LV and dyssynchronous contraction between the LV and RV. Echocardiographic and electroanatomic mapping of the LV in the presence of left bundle branch block (LBBB) demonstrate delayed activation of the basal posterolateral LV wall [1].

It is unclear whether intra- or interventricular dyssynchrony is more pathologic, though cohort studies suggest that patients with LBBB have worse prognosis and more severe HF symptoms [2,3].

CRT involves simultaneous or near-simultaneous pacing of the LV and RV to restore ventricular synchrony, which can improve LV systolic function and reduce the risk of clinical outcomes for selected patients with LV systolic dysfunction and mechanical dyssynchrony. Acute hemodynamic benefits of CRT may include increased systolic blood pressure, increased cardiac output, and increased contractility [4]. CRT enhances myocardial contractility without increasing myocardial oxygen consumption [5]. Chronic benefits of CRT include favorable remodeling of the LV, improved functional status, and decreased risk of adverse clinical outcomes. As examples:

●In the CARE-HF trial, CRT was associated with an increase in average LV ejection fraction (LVEF) of 3.7 percent at three months and 6.9 percent at 18 months; average LV end-systolic volume (LVESV) index decreased by 16.7 percent at three months and 29.6 percent at 18 months [6].

●Other studies found similar effects. In the MIRACLE trial at six months, LVEF increased 3.6 percent in CRT patients versus 0.4 percent in controls, and LVESV decreased 25.6 mL compared with no change in controls [7]. This relationship is graded; as LVESV decreased, survival improved incrementally [8].

The clinical benefits of CRT pacing on symptoms, death, and rehospitalization are discussed below. (See 'Indications' below.)

GENERAL APPROACH

Manage reversible causes of HF — Patients with potentially reversible causes of LV systolic dysfunction should be treated for such causes before considering a CRT device (algorithm 1). Reversible causes of LV dysfunction include toxin-mediated LV dysfunction, aortic regurgitation, ischemia, various tachyarrhythmias, and hyperthyroidism [9]. (See "Causes of dilated cardiomyopathy" and "Overview of the management of heart failure with reduced ejection fraction in adults".)

Implement optimal medical therapy — Patients with LV systolic dysfunction with LVEF ≤35 percent should be appropriately treated with a regimen of medications that may improve symptoms, reduce outcomes, and improve LV systolic function (table 1). The approach to selection of agents and management of the regimen of agents is discussed separately. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction".)

The duration of medical therapy prior to CRT device is determined by the observed and expected response of an individual to medical therapy; the latter is difficult to predict. In addition, we aim to decrease the number of procedures required to establish optimal cardiac implantable electronic device (CIED) therapy. Thus, it may be reasonable to proceed with CRT placement despite a relatively short duration of medical therapy in patients who will undergo implantation of another device (ie, pacemaker, ICD) or in patients whose LBBB or other characteristics are unlikely to improve with medical therapy. (See 'Ejection fraction >35 percent and <50 percent' below and 'Special circumstances' below.)

There are few data to inform the decision of when to proceed with CRT following medical therapy. One retrospective study suggested that in patients with nonischemic cardiomyopathy and LBBB, the response to medical therapy is minimal [10].

Reassess symptoms and cardiac function — After treatment of any reversible causes of LV systolic function and optimal medical therapy for HF with reduced ejection fraction (HFrEF), we reevaluate the patient's symptom severity, LVEF with echocardiography, and repeat an ECG to assess the rhythm, QRS morphology, and QRS duration. (See "Basic approach to delayed intraventricular conduction".)

Determine if an indication is present — Based upon symptom severity, LVEF, etiology of LV systolic dysfunction, QRS duration, and QRS pattern, we determine whether the patient would benefit from CRT. Additional studies (eg, magnetic resonance imaging) are not routinely used to assess the benefit of CRT. The main indications for CRT and other common reasons to evaluate for CRT are discussed elsewhere in this topic. (See 'Indications' below and 'Other scenarios' below and 'Special circumstances' below.)

Identify contraindications — Before CRT system placement, we evaluate for the presence of any relative or absolute contraindications. Common risk factors or barriers to CRT placement include:

●Relative contraindications

•Low likelihood of survival to one year – In general, CRT is unlikely to be beneficial in patients with coexisting conditions expected to limit survival with good functional capacity to less than one year [9]. Common examples of such comorbidities include:

-Chronic obstructive pulmonary disease – Patients with symptoms predominantly caused by severe chronic obstructive pulmonary disease (COPD) may not derive symptomatic benefit from CRT [11]. Clinically, identifying the cause of dyspnea in patients with both HF and COPD can be challenging. (See "Cardiopulmonary exercise testing in cardiovascular disease", section on 'Clinical applications'.)

-Chronic kidney disease – Patients with severe kidney function impairment may benefit less from CRT and may also not benefit from ICDs [12,13]. Median survival after an appropriate shock from a device with CRT and defibrillator functions in patients with severe kidney function impairment was only 90 days in one observational study [14]. The risk of device-related infection is also higher in this population [15].

Hemodialysis is associated with a high rate of device complications, including hematoma, pocket infection, bacteremia with endovascular lead infection, and compromise of hemodialysis access [16]. Patients on hemodialysis also may have limited access for intravascular lead placement.

•Older patients – Age is a factor in CRT device placement, but there is no upper limit of age at which CRT has been shown to be ineffective. However, in older patients, the effects of anesthesia and slower wound healing are important factors to consider when counseling patients who are older about the risks of CRT device placement.

•System upgrade to CRT – Most patients with HFrEF who have an existing device (eg, ICD, RV pacemaker) and who qualify for CRT placement should undergo CRT upgrade despite the higher risk of complications with CRT upgrade compared with de novo device implantation.

-In a randomized trial that included patients with HFrEF who had either prior RV pacing or prior ICD placement and a paced QRS duration ≥150 ms, random assignment to CRT upgrade was associated with a lower rate of HF hospitalizations at one year (5 versus 21 percent; hazard ratio [HR] 0.24, 95% CI 0.13-0.43) and a similar rate of death (6 versus 11 percent; HR 0.52, 95% CI 0.23-1.16) compared with patients who did not undergo CRT upgrade [17].

-In the REPLACE registry, the six-month major complication rate for CRT upgrade was higher than that of de novo implantations (18.7 versus 4.0 percent) [18].

●Absolute contraindications

•Active infection – Patients with active infection are at risk of anesthesia complications and seeding of the CRT system.

•Inability to receive appropriate anesthesia – CRT procedures may occasionally take more than two hours to complete, which may increase the likelihood of anesthetic and infectious complications. Further information on anesthesia for CIED procedures is discussed separately. (See "Cardiac implantable electronic devices: Periprocedural complications" and "Anesthetic considerations for electrophysiology procedures", section on 'Procedures for cardiac implantable electronic devices'.)

•Inability to participate in device follow-up – As with any CIED, follow-up to ensure safety and proper function of the device is required. Follow-up for a CRT system typically requires the patient to facilitate interrogation of the device approximately every three months as well as respond to any alerts that may arise prior to scheduled interrogations.

•Stage D heart failure – We avoid CRT in patients who are inotrope dependent or who have nonambulatory class IV HF symptoms despite optimal medical therapy. Patients who require inotropes have a high likelihood of death, need for cardiac transplantation, or left ventricular assist device (LVAD) regardless of CRT support. Studies that describe the benefit of CRT in this population suggest varying effectiveness and are subject to bias [19-21]. (See 'Nonambulatory class IV HF' below.)

Similarly, we avoid CRT placement in patients likely to undergo LVAD. Small studies in patients with LVADs suggests that RV pacing alone is equivalent if not superior to CRT in terms of functional status and ventricular tachyarrhythmia burden [22].

Discuss alternatives, risks, and benefits — For many patients, CRT is an additional therapy that may improve symptoms or reduce the risk of hospitalization or death. While there are no other therapies for patients with HFrEF that specifically treat dyssynchrony, other patients with similar symptom severity and degree of systolic dysfunction may benefit from other HF therapies (eg, transcatheter mitral valve edge-to-edge repair, heart transplantation).

Ultimately, the decision to pursue CRT should be informed by the best estimates of the benefits and risks in the context of shared decision making [23]. Beyond the broad indications for CRT, it has been difficult to predict the benefit of CRT [24]. Greater responses to CRT were observed with nonischemic etiology of cardiomyopathy, LV pacing at the site of latest mechanical or electrical contraction, when the percent of LV or biventricular pacing is high during follow-up after device implantation, and among females, but none of these have been rigorously confirmed [25-28].

Approximately one-third of CRT recipients are deemed "nonresponders," although the definition of "response" is not standardized [29,30]. A subset of patients may be "negative responders" and become worse with CRT [31]. Further details on the definition of response and maneuvers to optimize CRT programming are discussed separately. (See "Cardiac resynchronization therapy and conduction system pacing in heart failure: System implantation and programming", section on 'Identification of and approach to nonresponders'.)

The complications of CRT system placement for each type of CRT system are discussed separately. (See "Cardiac resynchronization therapy and conduction system pacing in heart failure: System implantation and programming".)

INDICATIONS

HF symptoms, LBBB with QRS ≥150 ms, EF ≤35 percent — In patients with optimally treated HF with reduced ejection fraction (HFrEF) with New York Heart Association (NYHA) class II to ambulatory class IV HF symptoms, LVEF ≤35 percent, sinus rhythm, and left bundle branch block (LBBB) with QRS duration ≥150 ms, we recommend placement of CRT (algorithm 1). This recommendation assumes that patients are likely to receive >95 percent pacing, which is most likely in patients with sinus rhythm but can occur in selected patients with atrial fibrillation (eg, atrioventricular node ablation). Patients who have a preexisting pacemaker or defibrillator who qualify for CRT should undergo an upgrade of their existing system to include CRT functionality.

In order to minimize the number of procedures required to achieve optimal cardiac electronic implantable device (CIED) therapy, all patients who will undergo CIED placement or upgrade should be evaluated for the appropriateness of an ICD. (See 'Simultaneous defibrillator placement' below and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".)

This approach is consistent with North American and European guidelines [32-34]. (See 'Society guideline links' below.)

Randomized clinical trials and meta-analyses have demonstrated that CRT reduces mortality, reduces hospitalizations, and improves functional status in patients with severely reduced LVEF, LBBB morphology, QRS duration ≥150 ms, and NYHA class II to IV HF symptoms. As examples:

●In the RAFT trial that included 1798 patients with NYHA class II or III HF symptoms, various QRS morphologies with QRS duration ≥120 ms (≥200 ms if paced), and LVEF ≤30 percent, patients assigned to placement of a device with CRT and defibrillator functions (CRT-D) had lower rates of mortality (21 versus 26 percent; hazard ratio [HR] 0.75, 95% CI 0.62-0.91) and hospitalization for HF (20 versus 26 percent; HR 0.68, 95% CI 0.56-0.83) compared with patients assigned to ICD alone [35]. Among prespecified subgroups, patients with a QRS ≥150 ms and those with a LBBB morphology had the greatest benefit of CRT.

In follow-up of this trial that included patients (n = 1050) enrolled at high-volume centers, patients assigned to CRT-D had a lower rate of death at 15 years (71 versus 76 percent; HR 0.8, 95% CI 0.69-0.92) [36].

●In a patient-level meta-analysis that included individual-level data from 3872 patients with NYHA class II to IV HF, LVEF ≤40 percent, and QRS ≥120 ms with predominantly LBBB morphology (78.4 percent), patients assigned to CRT had lower rates of mortality (HR 0.66, 95% CI 0.57-0.77) and mortality or HF hospitalization (HR 0.65, 95% CI 0.58-0.74) compared with controls [37]. Among multiple subgroup analyses, the mortality benefit of CRT varied by the QRS duration, with QRS duration of more than approximately 140 ms having the greatest benefit. Other characteristics (eg, NYHA class, LVEF, QRS morphology) did not clearly modify the effect of CRT. Patients with NYHA class IV HF composed only 3.8 percent of the sample.

●In an older meta-analysis of 14 randomized trials including 4420 patients (nearly all with NYHA class III or IV symptoms, mean QRS range 155 to 209 ms), patients assigned to CRT had a higher likelihood of improving by at least one NYHA class (59 versus 37 percent; relative risk [RR] 1.6, 95% CI 1.3-1.9) compared with controls. Those patients assigned to CRT had a lower rate of hospitalization, and all-cause mortality was reduced 22 percent, which was primarily attributable to a lower risk of HF-related death (RR 0.64, 95% CI 0.49-0.84) [38].

Older trials also suggest that CRT is more likely to increase six-minute walk distance and peak oxygen consumption compared with controls [39-41].

Other scenarios

LBBB with shorter QRS duration (120 to 149 ms)

●QRS ≥120 ms and <150 ms – In patients with optimally treated HFrEF with NYHA class II to ambulatory class IV HF symptoms, LVEF ≤35 percent, sinus rhythm, and LBBB who have a QRS duration ≥120 ms and <150 ms, we suggest CRT (algorithm 1). Factors that generally favor the placement of CRT in such patients include:

•QRS duration closer to 150 ms

•Need for cardiac pacing or ICD therapy

•More severe HF symptoms

•More severe LV systolic dysfunction

This approach is consistent with North American and European guidelines [32-34].

Since the main effect of CRT may be amelioration of intraventricular dyssynchrony, the benefits may be greater in patients with a LBBB of longer QRS duration and less or absent with a shorter QRS duration. Trials that included patients with a range of QRS durations (eg, ≥120 ms) showed an overall benefit of CRT, but these results may primarily reflect the effects in patients with a QRS duration ≥150 ms. Subgroup analyses from such trials are inconsistent:

•A large patient-level meta-analysis suggested that patients with LBBB and QRS <150ms had no clear mortality benefit with CRT [42].

•In another patient-level meta-analysis, there was a mortality benefit with CRT among patients with a QRS duration of more than approximately 140 ms, while those with a QRS <140 ms had an unclear benefit with CRT [37].

•In an older patient-level network meta-analysis, patients with QRS duration >120 ms had a mortality benefit with CRT, but this benefit was attenuated in patients with QRS duration 120 to 149 ms [43].

●QRS <120 ms – In patients with optimally treated HFrEF with NYHA class II to ambulatory class IV HF symptoms, LVEF ≤35 percent, sinus rhythm, and LBBB with QRS duration <120 ms, we provide optimal medical management and consider other appropriate therapies for HFrEF (eg, ICD, transcatheter mitral valve edge-to-edge repair in those with significant functional mitral regurgitation); CRT is not clearly beneficial.

In patients without marked dyssynchrony, it is biologically plausible that CRT has less or no effect; there is no clear evidence that patients with a QRS duration <130 ms benefit from CRT therapy. In trials that included such patients, outcome rates were similar in those assigned to CRT-D or to an ICD alone [44,45]. As an example, in the EchoCRT trial that included patients with a QRS duration <130 ms, overall mortality and cardiovascular mortality were possibly higher with CRT-D placement compared with ICD placement alone (29 versus 25 percent; HR 1.20, 95% CI 0.92-1.57) [45]. In meta-analyses, patients with a QRS <130 ms had no clear mortality benefit with CRT [37,43].

RBBB and intraventricular conduction delay — In patients with optimally treated HFrEF with NYHA class II to ambulatory class IV HF symptoms, LVEF ≤35 percent, sinus rhythm, QRS duration ≥120 ms, and with either right bundle branch block (RBBB) or a nonspecific intraventricular conduction delay, decisions about CRT are individualized (algorithm 1). In all such patients, a careful assessment by an electrophysiologist is required to help delineate the benefits and risks of CRT placement. In general, factors that favor CRT in this population include QRS duration >150 ms, more severe HF symptoms or LV dysfunction, concomitant need for another CIED, and de novo device implants, while factors that are less favorable for CRT include QRS duration <150 ms, less severe HF or LV dysfunction, and device upgrades.

North American and European guidelines give relatively weak recommendations for CRT in patients with non-LBBB who have a QRS ≥120 ms [32,33].

Since RBBB and intraventricular conduction delay (IVCD) may be amenable to CRT or obscure LV conduction abnormalities that CRT was designed to ameliorate, CRT may be effective in this population. However, trials that included such patients show an inconsistent effect of CRT. In addition, patients with a non-LBBB conduction delay were underrepresented in large trials of CRT. Examples of meta-analyses and trials include:

●In a patient-level meta-analysis, patients who had IVCD had lower rates of mortality with CRT, but patients with RBBB had no clear mortality benefit from CRT [42].

●In two earlier meta-analyses, CRT was of unclear benefit (ie, mortality or hospitalization) in subgroups of patients with either RBBB or intraventricular conduction delay [46,47].

●In one of the largest trials that included patients with LBBB and non-LBBB morphology, patients with LBBB had a lower rate of death with CRT compared with no CRT, but, in patients with RBBB, IVCD, or isolated RV pacing, the rates of death were similar in patients with or without CRT [35].

Asymptomatic LV systolic dysfunction — In patients with optimally treated HFrEF, LVEF ≤35 percent, sinus rhythm, and LBBB with QRS duration ≥150 ms but who do not have HF symptoms (ie, NYHA class I symptoms), we suggest CRT (algorithm 1). In similar patients with a QRS <150 ms, we monitor for the development of HF symptoms before placing a CRT system.

North American guidelines give a relatively weak recommendation for CRT in similar asymptomatic patients with LBBB and QRS ≥150 ms and do not recommend CRT in such patients with QRS duration <150 ms [32]. European guidelines make no specific recommendation and note that data are limited [33].

In trials and analyses that included patients with NYHA class I HF symptoms, CRT reduced the rate of HF hospitalizations and the incidence of symptomatic HF. The effect on mortality was less clear. Notably, patients with NYHA class I HF were often included in trials and analyses that predominantly included patients with NYHA class II HF symptoms. As examples:

●In a meta-analysis that pooled patients with NYHA class I and class II HF symptoms, CRT reduced the risk of mortality (11 versus 15 percent in controls; risk ratio [RR] 0.83, 95% CI 0.72-0.96) and HF hospitalization (14 versus 21 percent; RR 0.71, 95% CI 0.57-0.87) [48]. Notably, assignment to CRT did not clearly improve six-minute walk distance or quality of life in patients with class I or II HF symptoms.

●The MADIT-CRT trial included 1820 patients with either NYHA class I (28 percent) or class II HF symptoms who were randomly assigned to receive either a CRT-D or an ICD [39]. The patients with NYHA class I HF symptoms all had ischemic cardiomyopathy, while patients with NYHA class II HF symptoms had ischemic cardiomyopathy or nonischemic cardiomyopathy. Patients assigned to CRT-D had a lower rate of incident HF events (14 versus 23 percent; HR 0.59, 95% CI 0.47-0.74) but not death (6.8 versus 7.3 percent; HR 1.0, 95% CI 0.69-1.44) compared with patients who underwent ICD placement only.

●In the REVERSE trial, patients with NYHA class I (21 percent) or class II HF symptoms underwent placement of a CRT system that was randomly activated (n = 419) or inactivated (n = 191) [35]. Patients with an active CRT system had a lower rate of HF hospitalizations compared with those with an inactive system (4 versus 8 percent); the rate of mortality was similar between the two groups (2.1 versus 1.6 percent).

Ejection fraction >35 percent and <50 percent — For patients with optimally treated HFrEF with NYHA class II to ambulatory class IV HF symptoms, LBBB with QRS duration ≥120 ms with an LVEF >35 and <50 percent, and another indication for a CIED (eg, pacemaker for atrioventricular block, ICD for primary or secondary prevention of sudden cardiac death), we suggest CRT rather than placement of a traditional pacemaker or ICD alone (algorithm 1). In patients who do not require a CIED for another indication, the role of CRT is unclear and referral to an electrophysiologist is appropriate.

This approach is consistent with North American and European guidelines [32-34].

The rationale for CRT in this setting is based on indirect evidence from trials that included patients with LVEF ≤35 percent and one trial in patients with LVEF >35 and <50 percent. In the BLOCK-HF trial that included 691 patients with an indication for pacing, LVEF <50 percent, and NYHA class I to III symptoms, assignment to CRT had a lower rate of hospitalization for HF (HR 0.7, 95% CI 0.52-0.93) but not death (HR 0.83, 95% CI 0.61-1.14) compared with assignment to standard RV pacing [49].

Nonambulatory class IV HF — We avoid CRT placement in patients with nonambulatory class IV HF; instead, such patients should be evaluated for advanced HF therapies (eg, heart transplantation, left ventricular assist device placement). Nonrandomized, single-center studies suggest that CRT is not clearly effective in nonambulatory NYHA class IV HF patients [20].

Atrial fibrillation — The role of CRT in patients with atrial fibrillation is discussed separately (See "Cardiac resynchronization therapy in atrial fibrillation".)

SPECIAL CIRCUMSTANCES

LBBB-induced systolic dysfunction — In rare cases in which a thorough investigation suggests that left bundle branch block (LBBB) is the most likely cause of LV systolic dysfunction, treatment typically includes optimal medical therapy and CRT placement (algorithm 1). However, because it is difficult to determine whether LBBB is the cause or result of LV systolic dysfunction, the response to CRT may be variable. In a study from a single center, patients with LBBB, smaller LV dimension (LV end-diastolic dimension <58 mm, LV end-systolic dimension <48 mm), and shorter time from cardiomyopathy diagnosis (<24 months) were associated with a higher likelihood of normalization of LVEF after CRT placement [50].

Pacemaker-induced cardiomyopathy — Patients with a high burden of RV pacing can develop pacer-induced cardiomyopathy. In these patients, upgrade to CRT is reasonable (algorithm 1).

Planned pacemaker or ICD placement — In patients who require a pacemaker or ICD who have preexisting LV systolic dysfunction (ie, LVEF <50 percent), CRT pacing may be appropriate. The benefits of this approach are likely highest in patients expected to require ≥40 percent pacing. This issue is discussed elsewhere. (See 'Ejection fraction >35 percent and <50 percent' above.)

Congenital heart block — In patients with congenital heart block who require ventricular pacing, CRT pacing should be considered. The choice of device in such patients is discussed in detail elsewhere. (See "Congenital third-degree (complete) atrioventricular block", section on 'Role of cardiac physiologic pacing'.)

CHOICE OF CRT SYSTEM

Initial approach — In patients with HF with reduced ejection fraction (HFrEF) who have an indication for CRT, we suggest a coronary sinus lead as the initial approach to establishing CRT rather than left bundle branch area pacing (LBBAP) lead. His bundle pacing systems are rarely used for CRT due to a higher risk of complications compared with coronary sinus and LBBAP systems. (See 'Conduction system pacing' below.)

Epicardial lead placement, which requires a thoracotomy, is reserved for patients who cannot undergo transvenous lead placement or who have an indication for cardiac surgery, such as coronary artery bypass grafting or valve replacement [25]. (See 'Epicardial lead placement' below.)

Professional society guidelines include a weak preference for CRT with a coronary sinus lead [33,34].

This approach is influenced by the greater experience with coronary sinus lead placement, the higher likelihood of successful coronary sinus lead placement (>95 percent versus approximately 85 percent with conduction system pacing), and the relative abundance of data on the efficacy and safety of coronary sinus leads. In trials that established the benefit of CRT therapy in patients with HFrEF, the initial approach to lead placement was via the coronary sinus, and conduction system pacing was not an option. These studies are described in detail elsewhere in this topic. (See 'HF symptoms, LBBB with QRS ≥150 ms, EF ≤35 percent' above.)

Conduction system pacing may have higher rates of significant complications at implantation (eg, coronary artery injury, LV cavity perforation), and the long-term complications of conduction system leads (eg, battery drain, ability to extract the lead) are not well characterized. The comparative evidence is relatively modest and includes:

●A trial that included 40 patients with nonischemic cardiomyopathy and left bundle branch block (LBBB) showed that random assignment to CRT with a LBBAP lead was associated with a greater increase in LVEF at six months compared with CRT using a coronary sinus lead (difference in LVEF at six months 5.6 percent; 95% CI 0.3-10.9), but other important markers of CRT effectiveness (eg, LV end-diastolic dimension, six-minute walk time) were similar [51]. Lead dislodgement occurred in one patient assigned to LBBAP and none of the patients assigned to coronary sinus pacing. Though this direct comparison between coronary sinus pacing and conduction system pacing did not show large differences between the two methods, the sample size was too small and follow-up too short to conclusively establish the safety of conduction system pacing.

●In a registry that included 2533 patients with HFrEF who underwent CRT with an LBBAP lead, lead placement was successful in 84 percent of the 696 patients [52]. Complications related to LBBAP lead placement included intraprocedural perforation into the LV cavity (4 percent), ST-segment elevation in multiple leads (1 percent), and lead dislodgement (1.5 percent).

●In a study that included 100 patients with HF who underwent CRT using a coronary sinus lead (n = 51) or with an LBBAP lead (n = 49), HF hospitalization and mortality were similar between the two groups [53]. The rate of improvement in LVEF of >5 percent was similar between the two groups (86 versus 80 percent). One patient had a coronary sinus lead dislodgement.

Alternative approaches — In patients who cannot undergo placement of a coronary sinus lead, the approach to placement of a conduction system pacing lead or an epicardial lead is individualized to the patient's characteristics and the center's experience with alternative lead placement.

Conduction system pacing — In patients in whom a coronary sinus lead cannot be placed, LBBAP is an option for CRT. His bundle leads are another form of conduction system pacing but are more likely to become dislodged when compared with LBBAP leads. Further details on the performance of both forms of conduction system pacing are described elsewhere in this topic and separately. (See 'Initial approach' above and "Cardiac resynchronization therapy and conduction system pacing in heart failure: System implantation and programming".)

In studies that compared the relative safety of LBBAP and His bundle lead placement, His bundle lead placement was associated with more complications. In a meta-analysis of retrospective studies, LBBAP had higher procedural success (91 versus 81 percent) and lower complication rates (1.8 versus 5.2 percent) that included lower rates of lead failure or deactivation (0.2 versus 3.9 percent) [54].

Epicardial lead placement — A CRT lead can be placed on the epicardial surface of the lateral LV via a lateral thoracotomy or during cardiac surgery performed for a separate indication. Patients in whom epicardial lead placement should be considered include:

●Failed placement of a percutaneous lead – In patients who cannot undergo traditional coronary sinus lead placement and in whom the benefits of CRT outweigh the risk of lead placement, epicardial lead placement is an option for CRT pacing. However, the efficacy and safety of this approach are determined by the patient's suitability for surgery and institutional surgical experience.

The evidence on epicardial lead placement includes small studies and one trial, which describe variable rates of morbidity, mortality, and successful lead implantation [55-58]. As examples:

•In a randomized trial that included 80 patients with HFrEF from 2008, patients randomly assigned to epicardial lead placement had a longer length of intensive care unit stay (3.8 versus 0.34 days) and longer ventilation time (3.2 versus 0.3 hours) compared with those with coronary sinus lead placement [58].

•Notably, one study described unfavorable anterior lead placement in 44 percent of patients undergoing epicardial lead placement and in only 5 percent of patients undergoing coronary sinus lead placement [57].

●Patients who will undergo cardiac surgery for a separate indication – In patients with HFrEF who will undergo cardiac surgery (eg, coronary artery bypass grafting) and who have an indication for CRT, it is reasonable to place an epicardial lead at the time of surgery rather than attempt coronary sinus lead placement after surgery. This approach is motivated by the desire to avoid the need for a subsequent thoracotomy if placement of a coronary sinus lead is not technically feasible, which occurs in approximately 3 to 5 percent of patients [59].

Simultaneous defibrillator placement — We generally choose the type of device based on whether the patient meets separate criteria for CRT and ICD placement. In patients who meet the usual criteria for both CRT and ICD, we generally place a device with CRT and defibrillator functions (CRT-D). In cases in which the benefit of CRT device placement is likely high and the benefit of ICD therapy is unclear, the decision to place a CRT-D or a pacemaker with a CRT function only (CRT-P) is individualized. This decision typically includes input from an electrophysiologist and the patient's preferences. Factors that may influence this decision include:

●Age – The role of age in the benefit of ICD therapy is discussed separately. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'Older adults and patients with comorbidities'.)

●Nonischemic cardiomyopathy – Patients with a nonischemic cardiomyopathy and LBBB who have indications for both CRT and an ICD should typically undergo CRT-D implantation. While CRT-P may sufficiently reduce the risk of sudden cardiac death in patients with nonischemic cardiomyopathy, there is no trial that directly addresses whether CRT-P is superior to CRT-D. In the DANISH trial, this issue was indirectly and inconclusively evaluated [60]. (See "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF", section on 'DANISH trial'.)

Major society guidelines do not delineate the role of CRT-D versus CRT-P placement [32-34].

There are no direct comparisons of the efficacy of CRT-P in patients who meet criteria for an ICD. While there are indirect comparisons between CRT-P and CRT-D, the aggregate data suggest that CRT-D has a lower risk of mortality than CRT-P. In a patient-level network meta-analysis of randomized trials, CRT-D likely reduced the risk of mortality more than CRT-P (hazard ratio 0.81, 95% CI 0.67–0.99) [43].

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: Heart failure 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 5^th to 6^th 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 10^th to 12^th 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

●Effects of dyssynchrony and motivation for cardiac resynchronization pacing – In the cardiomyopathic state, dyssynchrony leads to inefficient left ventricular (LV) contraction that may reduce cardiac output, exacerbate functional mitral regurgitation, and worsen adverse LV remodeling (eg, dilation).

●General approach to cardiac resynchronization therapy (CRT)

•Manage reversible causes of systolic dysfunction. (See 'Manage reversible causes of HF' above.)

•Implement optimal medical therapy for heart failure (HF) with reduced ejection fraction (HFrEF) (table 1) and assess the response. (See 'Implement optimal medical therapy' above and 'Reassess symptoms and cardiac function' above.)

•Identify indications. (See 'Indications' above.)

•Identify contraindications. (See 'Identify contraindications' above.)

•Discuss alternatives, risks, benefits. (See 'Discuss alternatives, risks, and benefits' above.)

●HF symptoms, LBBB ≥150ms, LVEF ≤35 percent – In patients with optimally treated HFrEF with New York Heart Association (NYHA) class II to ambulatory class IV HF symptoms, LV ejection fraction (LVEF) ≤35 percent, sinus rhythm, and left bundle branch block (LBBB) with QRS duration ≥150 ms, we recommend placement of CRT (algorithm 1) (Grade 1A). (See 'HF symptoms, LBBB with QRS ≥150 ms, EF ≤35 percent' above.)

●Other indications

•LBBB with shorter QRS duration (120 to 149 ms) – In patients with optimally treated HFrEF with NYHA class II to ambulatory class IV HF symptoms, LVEF ≤35 percent, sinus rhythm, and LBBB who have a QRS duration ≥120 ms and <150 ms, we suggest CRT (algorithm 1) (Grade 2B). Trials that included patients with a range of QRS durations (eg, ≥120 ms) showed an overall benefit of CRT, but these results may primarily reflect the effects in patients with a QRS duration ≥150 ms. (See 'LBBB with shorter QRS duration (120 to 149 ms)' above.)

•RBBB and intraventricular conduction delay – In patients with optimally treated HFrEF with NYHA class II to ambulatory class IV HF symptoms, LVEF ≤35 percent, sinus rhythm, QRS duration ≥120 ms, and with either right bundle branch block (RBBB) or a nonspecific intraventricular conduction delay (IVCD), decisions about CRT are individualized (algorithm 1). In such patients, a careful assessment by an electrophysiologist is required to help delineate the benefits and risks of CRT placement. (See 'RBBB and intraventricular conduction delay' above.)

•Asymptomatic LV systolic dysfunction – In patients with optimally treated HFrEF, LVEF ≤35 percent, sinus rhythm, and LBBB with QRS duration ≥150 ms but who do not have HF symptoms (ie, NYHA class I symptoms), we suggest CRT (algorithm 1) (Grade 2B). In similar patients with a QRS duration <150 ms, we monitor for the development of HF symptoms before placing a CRT system. (See 'Asymptomatic LV systolic dysfunction' above.)

•Ejection fraction >35 and <50 percent – For patients optimally treated HFrEF with NYHA class II to ambulatory class IV HF symptoms, sinus rhythm, LBBB with QRS duration ≥120 ms with an LVEF >35 and <50 percent, and another indication for an implantable device (eg, atrioventricular block, implantable cardioverter-defibrillator [ICD]), we suggest CRT rather than placement of a dual chamber device or an isolated ICD, respectively (algorithm 1) (Grade 2B). (See 'Ejection fraction >35 percent and <50 percent' above.)

•Nonambulatory class IV HF – We avoid CRT placement in patients with nonambulatory class IV HF; instead, such patients should be evaluated for advanced HF therapies (eg, heart transplantation, left ventricular assist device [LVAD] placement). (See 'Nonambulatory class IV HF' above.)

•Atrial fibrillation – Additional evidence on the effects of CRT in patients with atrial fibrillation is discussed separately. (See "Cardiac resynchronization therapy in atrial fibrillation".)

●Special circumstances – Patients in which CRT may have a role not suggested by standard indications include (algorithm 1):

•LBBB-induced systolic dysfunction. (See 'LBBB-induced systolic dysfunction' above.)

•Planned pacemaker or ICD placement. (See 'Planned pacemaker or ICD placement' above.)

•Congenital heart block. (See "Congenital third-degree (complete) atrioventricular block", section on 'Role of cardiac physiologic pacing'.)

●Initial choice of CRT system – In patients with HFrEF who have an indication for CRT, we suggest a coronary sinus lead as the initial approach to establishing CRT rather than other methods of CRT pacing (eg, left bundle branch area pacing [LBBAP]) (Grade 2C).

●Alternative approaches – In patients who cannot undergo placement of a coronary sinus lead, the approach to placement of a conduction system pacing lead or an epicardial lead is individualized to the patient's characteristics and the center's experience with alternative lead placement. The options include:

•Conduction system pacing – In patients in whom a coronary sinus lead cannot be placed, LBBAP is an option for CRT. His bundle pacing systems are rarely used for CRT due to a higher risk of complications compared with LBBAP systems. (See 'Conduction system pacing' above.)

•Epicardial lead placement – Epicardial lead placement, which requires a thoracotomy, is reserved for patients who cannot undergo transvenous lead placement or who have an indication for cardiac surgery, such as coronary artery bypass grafting or valve replacement. (See 'Epicardial lead placement' above.)

ACKNOWLEDGMENTS — 

The editorial staff at UpToDate acknowledges Leslie Saxon, MD, Teresa DeMarco, MD, and Wilson Colucci, MD, who contributed to earlier versions of this topic review.