incidence of appropriate ICD therapy [61,62]. However, a MADIT-CRT post hoc analysis demonstrated that although the risk of ventricular tachyarrhythmias among CRT patients who had improved LVEF and no longer met a primary prevention ICD indication was reduced by over 50 percent, there remained a significant risk of arrhythmias during the ensuing two years [63]. Risks The risks of CRT are greater than those of single- or dual-chamber devices, as LV lead implantation increases procedural complexity, increases risk of infection, and reduces battery longevity, necessitating more frequent generator changes. In addition, there are reports of LV pacing inducing ventricular arrhythmias in a minority of CRT recipients [64]. Complications of CRT are discussed separately. (See "Cardiac resynchronization therapy in heart failure: System implantation and programming".) SHARED DECISION MAKING FOR CRT General considerations Because of the heterogeneity of benefit conferred by treatment as a function of patient factors, the lack of compelling data in some patient populations, and the frequency of comorbidities in patients with HF, decision making around CRT is often complex. Ultimately, the decision to pursue the therapy should be informed by best estimates of both benefits and risks in the context of shared decision making, which is defined as selecting therapy from the reasonable options that is aligned with the patient s values, goals, and preferences [65]. Indeed, the ACC/AHA/HRS guidelines specifically recommend informed shared decision making as integral to the provision of implantable cardioverter-defibrillator (ICD) and CRT therapy. Because many patients considered for CRT have advanced symptomatic HF, the discussion about device therapy will be part of a larger discussion about prognosis. (See "Palliative care for patients with advanced heart failure: Indications and systems of care", section on 'Disease course and prognosis'.) The capacity to estimate the benefits of CRT varies substantially based upon patient characteristics. In cases where benefits are not well established, the limitations of existing data should be openly acknowledged in the decision-making process. A patient-level analysis of five randomized trials of CRT found that quality of life (QoL) benefits at three months were predicted https://www.uptodate.com/contents/cardiac-resynchronization-therapy-in-heart-failure-indications-and-choice-of-system/print 12/32 7/6/23, 10:50 AM Cardiac resynchronization therapy in heart failure: Indications and choice of system - UpToDate by patient age, baseline QoL, and QRS duration [66]. Such statistical models may be useful in determining the likely advantages of undergoing CRT implantation. Further, clinicians must also elicit and consider the patient's care-related goals and preferences in order to achieve shared decision making [67]. Individualized risk-benefit assessment Because CRT is associated with risk, both acutely during implantation and chronically, the risk-benefit ratio of CRT implant must be considered in each individual patient, particularly in those with less compelling indications. The CRT implantation procedure is longer, entails more procedural risk, and may increase the risk of infection compared with standard ICD or pacemaker implantations. LV leads have an increased risk of dislodgment or pacing the phrenic nerve compared with traditional RV leads. Battery longevity is generally shorter for CRT devices compared with conventional ICDs or pacemakers. Another consideration is that not all patients with similar indications for CRT derive similar benefits, but a means of identifying patients with indications for CRT who will fail to benefit has not been established. Approximately one-third of CRT recipients are deemed "nonresponders" [68], although the definition of "response" is not standardized [69]. Definitions of response include improvement in exercise capacity, improved QoL via standardized assessments, improvement in New York Heart Association (NYHA) status by at least one class, prevention of HF hospitalizations, and LV reverse remodeling. A subset of patients may be "negative responders" and become worse with CRT. Increased risk with an upgrade procedure Intervening on a device system already in place (ie, CRT "upgrade") entails increased risk of infection and complications compared with de novo implant or generator change only. In the REPLACE registry, the six-month major complication rate for CRT upgrades was 18.7 percent, compared with 4.0 percent for patients undergoing generator change only [70]. The threshold for upgrading an existing device to CRT is thus higher than for a de novo implant. A stand-alone "upgrade" procedure in patients with an existing pacemaker or ICD should be considered only after careful consideration of the risk-benefit balance. Factors associated with less benefit from CRT Greater scar burden, as assessed by either myocardial perfusion or cardiovascular magnetic resonance imaging, is associated with less improvement in LV ejection fraction, less reverse remodeling, and higher mortality among patients treated with CRT [71]. However, there are no randomized trials assessing whether patients with high scar burden benefit less from CRT. https://www.uptodate.com/contents/cardiac-resynchronization-therapy-in-heart-failure-indications-and-choice-of-system/print 13/32 7/6/23, 10:50 AM Cardiac resynchronization therapy in heart failure: Indications and choice of system - UpToDate As discussed above, among patients treated with CRT, non-left bundle branch block (LBBB) QRS patterns, particularly right bundle branch block, are associated with less reverse remodeling and higher mortality compared with LBBB. (See 'Groups unlikely to benefit' above.) As discussed above, a native QRS duration between 120 and 149 ms predicts less clinical benefit from CRT than QRS duration 150 ms or greater. (See 'Groups unlikely to benefit' above.) Because milder HF symptoms are associated with a lower baseline risk of morbidity and mortality, the estimated absolute risk reduction from CRT is lower in those with less severe symptoms. For patients with less compelling indications and in patients for whom CRT would be a stand-alone upgrade procedure rather than a de novo implant, NYHA functional class is an important factor in decision making, as the risk-benefit balance may favor CRT in more advanced HF symptoms and not favor CRT in those patients with less severe symptoms. Competing causes of cardiopulmonary morbidity and mortality Patients with severe chronic obstructive pulmonary disease (COPD) may not derive symptomatic benefit from CRT if their symptoms are predominantly caused by COPD [72]. Clinically, identifying the cause of dyspnea in patients with both HF and COPD can be challenging. Patients with severe renal insufficiency may benefit less from CRT and may also not benefit from ICDs [73,74]. Median survival after an appropriate CRT-D shock in patients with severe renal insufficiency was only 90 days in one observational study [75]. The risk of device- related infection is also higher in this population [24]. Hemodialysis is associated with a high rate of device complications, including hematoma, pocket infection, bacteremia with endovascular lead infection, and compromise of hemodialysis access [76]. Patients on hemodialysis also may have limited access for intravascular lead placement. There are no randomized trials demonstrating mortality benefit in older adult patients, particularly those over 80 years of age. The risk of sudden cardiac death decreases with advancing age, whereas the risk of progressive pump failure increases. CRT-pacemaker may be a better option in clinically eligible older patients with significant symptoms of HF compared with CRT-defibrillator. (See 'Indications for referral for CRT' above.) https://www.uptodate.com/contents/cardiac-resynchronization-therapy-in-heart-failure-indications-and-choice-of-system/print 14/32 7/6/23, 10:50 AM Cardiac resynchronization therapy in heart failure: Indications and choice of system - UpToDate CONTRAINDICATIONS General contraindications to placement of a cardiac implantable electronic device such as active bloodstream infection and anesthetic concerns also apply to potential candidates for CRT implantation. (See "Anesthetic considerations for electrophysiology procedures", section on 'Procedures for cardiac implantable electronic devices'.) For patients in whom transvenous placement of CRT is not feasible, including those lacking subclavian access, a surgical approach may be an alternative. (See 'Choice of CRT system' below.) We concur with guidelines that CRT is not indicated in patients whose frailty or comorbidities limit expected survival with good functional capacity to less than one year [8]. We avoid CRT in the following clinical settings in which CRT is unlikely to be of benefit: Although there are no high-quality studies that examine the use of CRT in patients receiving mechanical circulatory support (eg, LV assist devices [LVAD]), the benefit of CRT in this group of patients is likely low given that the LVAD subsumes much of the cardiac output generated by the LV. De novo CRT should not be provided to these patients. The role of preexisting CRT in this population has not been conclusively studied, although a small study suggests that RV pacing alone is equivalent if not superior to CRT in terms of functional status and ventricular tachyarrhythmia burden [77]. This study supports our practice of deactivating CRT in patients with LVADs, which has the added benefit of battery preservation. If patients with a history of ventricular arrhythmias have recurrences with CRT deactivation, anecdotal experience suggests that reactivation may reduce the risk of recurrent arrhythmias. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device".) Inotrope-dependent patients have a markedly increased risk of death, need for cardiac transplant, or transition to LVAD support even with CRT as compared with non-inotrope- dependent patients. The benefits of CRT in this population appear to be limited [48]. We avoid CRT in these patients unless a strong indication exists. Patients who possibly should not receive CRT include those in whom the procedure or presence of multiple intravascular leads are associated with increased complications. The role of CRT in patients with end-stage kidney disease is uncertain given the risk of complications and uncertain benefit. (See 'Groups unlikely to benefit' above.) https://www.uptodate.com/contents/cardiac-resynchronization-therapy-in-heart-failure-indications-and-choice-of-system/print 15/32 7/6/23, 10:50 AM Cardiac resynchronization therapy in heart failure: Indications and choice of system - UpToDate CHOICE OF CRT SYSTEM Initial approach In patients with HF with reduced ejection fraction (HFrEF) who have an indication for CRT, we suggest placement of a coronary sinus lead as the initial approach to establishing CRT, rather than conduction system pacing. Epicardial lead placement is reserved for patients who cannot undergo coronary sinus lead placement or who have an indication for cardiac surgery, such as coronary artery bypass grafting or valve replacement [78]. (See 'Epicardial lead placement' below.) Professional society guidelines also have a weak preference for CRT with a coronary sinus lead compared with conduction system pacing [79]. Our approach is influenced by our 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 greater amount of data on the efficacy and safety of coronary sinus leads. 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 unknown. The evidence includes: 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 [15-19]. These studies are described in detail elsewhere in this topic. (See 'For QRS duration 150 ms' above.) In a trial that included 40 patients with nonischemic cardiomyopathy and left bundle branch block, random assignment to CRT with a left bundle branch area pacing (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 between the two groups [80]. 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 low and follow-up too short to conclusively establish the safety of conduction system pacing. https://www.uptodate.com/contents/cardiac-resynchronization-therapy-in-heart-failure-indications-and-choice-of-system/print 16/32 7/6/23, 10:50 AM Cardiac resynchronization therapy in heart failure: Indications and choice of system - UpToDate In a registry that included 2533 patients who underwent CRT with an LBBAP lead, placement of the lead was successful in 84 percent of the 696 patients with HF [81]. In the overall sample, 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 an LBBAP lead (n = 49), HF hospitalization and mortality were similar between the two groups [82]. 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 experience with alternative lead placement. Conduction system pacing Pacing of the His bundle or left bundle branch via a lead in the right ventricle fixed to the septum (ie, conduction system pacing) can be used to resynchronize the right and left ventricle. Leads placed in this position may be more unstable, may injure the septal coronary arteries, and may be more difficult to extract, particularly left bundle branch area pacing leads [83]. In patients who cannot undergo placement of a coronary sinus lead, the decision to implant a CRT system with a conduction system pacing lead (ie, His bundle lead, LBBAP lead) is individualized to the patient and depends on the implanting center's experience with conduction system lead placement. Conduction system pacing is a reasonable option for CRT in patients in whom epicardial lead placement via a surgical approach is undesirable. Professional guidelines describe a similar approach to conduction system pacing [84]. 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. https://www.uptodate.com/contents/cardiac-resynchronization-therapy-in-heart-failure-indications-and-choice-of-system/print 17/32 7/6/23, 10:50 AM Cardiac resynchronization therapy in heart failure: Indications and choice of system - UpToDate The evidence on epicardial lead placement includes small studies and one trial, which describe variable rates of morbidity, mortality, and successful lead implantation [85-88]. 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 venous lead placement [88]. Notably, one study described unfavorable anterior lead placement in 44 percent of patients undergoing epicardial lead placement and 5 percent of patients undergoing coronary sinus lead placement [87]. 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 attempting 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 [89]. 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." th th The Basics patient education pieces are written in plain language, at the 5 to 6 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 th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. https://www.uptodate.com/contents/cardiac-resynchronization-therapy-in-heart-failure-indications-and-choice-of-system/print 18/32 7/6/23, 10:50 AM Cardiac resynchronization therapy in heart failure: Indications and choice of system - UpToDate 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 Rationale for CRT Cardiac resynchronization therapy (CRT) involves pacing of the left and right ventricles to restore ventricular synchrony and thus improve left ventricular (LV) systolic function, symptoms of heart failure (HF), survival for selected patients with LV systolic dysfunction, and electrocardiographic evidence of dyssynchrony. (See 'Rationale for CRT' above.) CRT for patients in sinus rhythm Indications for CRT for patients in sinus rhythm are based upon LV ejection fraction (LVEF), QRS duration, QRS morphology, New York Heart Association (NYHA) functional class, and need for ventricular pacing. The recommendations are predicated on a discussion with the patient about the risks and benefits of the procedure in the context of shared decision making. The approach is as follows (see 'CRT indications in sinus rhythm' above): For patients with LVEF 35 percent The following general indications apply to patients with LVEF 35 percent on optimal evidence-based medical therapy for at least three months after initial diagnosis (or for at least 40 days after myocardial infarction) and after identification and treatment of any reversible causes of persistent HF (such as myocardial ischemia or tachycardia-induced cardiomyopathy) ( algorithm 1) (see 'For patients with LVEF 35 percent' above and 'Evidence for general indications' above): QRS 150 ms with LBBB For patients with QRS 150 ms with left bundle branch block (LBBB) and NYHA class II to ambulatory class IV HF, we recommend referral for CRT (Grade 1A). These patients also meet criteria for implantable cardioverter- defibrillator (ICD) therapy for primary prevention of sudden cardiac death. (See 'For QRS duration 150 ms' above and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) We also suggest referral for CRT in patients with NYHA class I HF and ischemic cardiomyopathy (ICM) (Grade 2B). Patients with ICM with LVEF 30 percent on medical therapy also meet criteria for ICD placement. https://www.uptodate.com/contents/cardiac-resynchronization-therapy-in-heart-failure-indications-and-choice-of-system/print 19/32 7/6/23, 10:50 AM Cardiac resynchronization therapy in heart failure: Indications and choice of system - UpToDate Based on indirect evidence from patients with ICM, some experts (including the authors of this topic) also refer patients with NYHA class I HF and nonischemic cardiomyopathy for an individualized risk-benefit assessment of CRT. These patients do not generally meet criteria for ICD placement. (See 'For QRS duration 150 ms' above and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF".) QRS 150 ms with non-LBBB For patients with QRS 150 ms with non-LBBB pattern and NYHA functional class III or ambulatory class IV HF symptoms, we suggest referral for CRT (Grade 2B). For patients with mild (NYHA class II) HF symptoms, we refer for an individualized risk-benefit assessment of CRT. QRS <150 ms For patients with QRS 130 to 149 ms with LBBB and NYHA class II to ambulatory class IV HF, we suggest referral for CRT (Grade 2B). (See 'For QRS duration 120 to 149 ms and/or non-LBBB morphology' above.) For patients with QRS 120 to 149 ms with non-LBBB pattern, persistent NYHA functional class III or ambulatory class IV HF, and recurrent HF hospitalizations despite optimal medical therapy, we refer for an individualized risk-benefit assessment of CRT. (See 'For QRS duration 120 to 149 ms and/or non-LBBB morphology' above.) For patients with LVEF between 35 and 50 percent For most patients with LVEF >35 and <50 percent, the benefits of CRT are not likely to outweigh the risks. However, CRT may be of benefit in the following select circumstances ( algorithm 2) (see 'For patients with LVEF between 35 and 50 percent' above): For patients who require a pacemaker (including patients undergoing atrioventricular junction ablation), have an LVEF <50 percent, and are anticipated to require frequent ventricular pacing (>40 percent of the time), we suggest referral for CRT (Grade 2B). (See 'Evidence for patients with LVEF between 35 and 50 percent' above.) For patients with QRS duration 150 ms with LBBB (native or paced) and persistent severe HF (NYHA functional class III or IV) despite optimal evidence-based medical therapy for at least three months, we refer for an individualized risk-benefit assessment of CRT-pacemaker (CRT-P). The efficacy of CRT in this population is not established. The rationale for CRT in this setting is based upon indirect evidence https://www.uptodate.com/contents/cardiac-resynchronization-therapy-in-heart-failure-indications-and-choice-of-system/print 20/32 7/6/23, 10:50 AM Cardiac resynchronization therapy in heart failure: Indications and choice of system - UpToDate from trials in patients with LVEF 35 percent and a single trial in pacemaker candidates. (See 'Evidence for patients with LVEF between 35 and 50 percent' above.) CRT for patients not in sinus rhythm Recommendations for patients with persistent atrial fibrillation are discussed separately. (See "Cardiac resynchronization therapy in atrial fibrillation".) Choice of CRT with or without defibrillator functionality CRT-P and CRT-defibrillator (CRT-D) should be discussed with all patients referred for CRT. Those populations with less likelihood of incremental benefit from CRT-D compared with CRT-P include older patients, patients without coronary artery disease (particularly if the LV is not dilated), and pacemaker-dependent patients. (See 'Choice between CRT-D versus CRT-P' above.) Contraindications General contraindications to placement of a cardiac implantable electronic device (such as active bloodstream infection) apply to potential candidates for CRT implantation. We also avoid CRT implantation in patients unlikely to benefit from it, such as patients whose comorbidities or frailty limit survival with good functional capacity to less than one year. (See 'Contraindications' above.) Choice of CRT system In patients with HF with reduced ejection fraction (HFrEF) who have an indication for CRT, we suggest placement of a coronary sinus lead as the initial approach to establishing CRT, rather than conduction system pacing (eg, left bundle branch area pacing [LBBAP], His bundle pacing) (Grade 2C). (See 'Alternative approaches' above and 'Conduction system pacing' above.) Epicardial lead placement is reserved for patients who cannot undergo coronary sinus 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. Use of UpToDate is subject to the Terms of Use. 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