2021 ESC Guidelines on Cardiac Pacing and Cardiac Resynchronization Therapy: Highlights and Major Changes

The European Society of Cardiology (ESC) released the 2021 Guidelines on Cardiac Pacing and Cardiac Resynchronization Therapy during ESC Congress 2021. The following are highlights and key updates from the document:

1. Gender differences in pacing
There appears to be a difference in pacing indications and rates of complications between male and female patients. Male patients primarily require pacing for atrioventricular block (AVB) rather than sinus nodal dysfunction and atrial fibrillation (AF) with bradycardia. Female patients were observed to have significantly higher rates of adverse events driven by pneumothorax, pericardial effusion, and pocket hematomas, possibly explained by anatomical differences.1,2

2. Evaluation of pacing indications
During initial evaluation of symptomatic bradycardia and conduction system disease, more emphasis is focused on a detailed patient history and a comprehensive physical exam. Carotid sinus massage is now recommended (Class I) in patients with syncope compatible with a reflex mechanism or with symptoms related to pressure/manipulation of the carotid sinus area once carotid stenosis is ruled out. Other noninvasive tests including 12 lead ECG, ambulatory ECG monitoring, exercise testing, ambulatory echocardiography monitoring, and multimodality imaging (cardiac magnetic resonance, computed tomography or positron emission tomography) in patients with suspected specific diagnoses/pathologies continues to be the cornerstone of pacing evaluation.3 Progressive cardiac conduction disease should be considered in young individuals (<50 years) with structurally normal hearts and genetic testing should be considered in those with a positive family history of conduction abnormalities, pacemaker implants, or sudden death.4 Patients with asymptomatic nocturnal bradyarrhythmias or cardiac conduction diseases should be evaluated for obstructive sleep apnea (OSA). Diagnosed OSA should be treated with continuous positive airway pressure ventilation and weight loss as appropriate treatment reduces episodes of bradycardia significantly.5

3. Updates on indications for cardiac resynchronization therapy (CRT)
CRT is a highly effective treatment in patients with heart failure with reduced ejection fraction (HFrEF) and bundle branch blocks (BBB). Compared to the 2013 guideline, CRT indications for HFrEF patient in sinus rhythm (SR) in the 2021 guideline raised the lower QRS duration threshold from 120ms to 130ms.6 Although trials suggest there might be potential benefits for all patients with LBBB regardless of QRS duration, the Echo-CRT trial suggested possible harm from CRT when echocardiographic mechanical dyssynchrony in patients with QRS duration <130ms were studied.7 In the 2021 guideline, CRT is not indicated in patients with HF and QRS duration <130ms without an indication for RV pacing.

In patients with permanent AF and HF with left ventricular ejection fraction (LVEF) ≤35% and NYHA class III and IV, the same indications for patients in SR continue to be recommended, given that atrioventricular junctional (AVJ) ablation is performed in those patients with incomplete (<90-95%) biventricular capture due to AF. More detailed recommendations were provided for patients with symptomatic AF and an uncontrolled heart rate who are candidates for AVJ ablation irrespective of QRS duration. CRT is recommended in patients with HFrEF, CRT rather than standard RV pacing should be considered in patients with HF with mid-ranged EF, and CRT may be considered in patients with HF with preserved EF after RV pacing. The use of His-bundle pacing (HBP) and left bundle branch pacing (LBBP) as novel ways to deliver CRT in these patient populations is promising but requires further validation of safety and efficacies in large RCTs.

Since the 2013 guideline on patients with reduced LVEF and conventional indications for antibradycardia pacing, randomized trials, especially the BLOCK-HF study, have proven superiority of CRT over RV pacing in those patients.8 In the 2021 guideline, CRT rather than RV pacing is recommended (Class I, Level A from Class IIa, Level B in 2013) for patients with HFrEF (<40%) regardless of NYHA class who have an indication for ventricular pacing and high-degree AVB in order to reduce morbidity, including patients with AF.

4. Alternative pacing modalities
Conduction system pacing including HBP and LBBP engage the native physiological electrical conduction system and restore conduction in selected patients with high-degree AVB and shorten QRS duration in selected patients with BBB. HBP is gaining more popularity as an alternative pacing modality in patients with RV pacing and CRT indications. However, HBP capture thresholds are on average higher and sensing amplitudes lower compared to RV pacing, potentially leading to shorter battery life, ventricular under-sensing and atrial/His over-sensing.9 Therefore, device programming tailored to specific requirements of HBP is recommended in this current guideline. Detailed recommendations of HBP in different clinical scenarios are discussed in section 7 of the 2021 guideline. More ongoing evidence is needed to evaluate clinical benefits and safety comparing HBP and LBBP to CRT and traditional RV pacing. Leadless intracardiac pacemakers can be considered in patients who only require single-chamber pacing as an alternative to transvenous pacing when no upper extremity venous access exists or when risk of device pocket infection is particularly high, such as previous infection and patients on hemodialysis. However, its use is limited by potential difficulties with retrieval.

5. Pacing after transcatheter aortic valve implantation (TAVI)
Limited guidance was provided in the 2013 guideline on pacing after TAVI. With more evidence available, permanent pacing is currently recommended in patients with complete or high-degree AVB that persists for 24-48h or with new-onset alternating BBB after TAVI (Class I) compared to 7 days of clinical observation for reversibility in the 2013 guideline. RBBB is the most consistent and powerful predictor for permanent pacemaker implantation after TAVI. Early permanent pacing (immediately after procedure or within 24 hours) should be considered in patients with pre-existing RBBB who develop any further conduction disturbance during or after TAVI (Class IIa). New-onset LBBB is the most common conduction abnormality after TAVI due to anatomical proximity of left bundle branch and aortic valve. In patients with new LBBB with QRS >150ms or PR >240ms and dynamic progression, extended 5-day in hospital monitoring should be considered. In those without further prolongation during 48h after TAVI and those with pre-existing conduction abnormalities who develop prolongation of QRS or PR>20ms after TAVI, ambulatory ECG monitoring or electrophysiology study can be considered.


  1. Mohamed MO, Volgman AS, Contractor T, et al. Trends of sex differences in outcomes of cardiac electronic device implantations in the United States. Can J Cardiol 2020;36:69-78.
  2. Moore K, Ganesan A, Labrosciano C, et al. Sex differences in acute complications of cardiac implantable electronic devices: implications for patient safety. J Am Heart Assoc 2019;8:e010869.
  3. Glikson M, Nielsen JC, Kronborg MB, et al. 2021 ESC guidelines on cardiac pacing and cardiac resynchronization therapy. Eur Heart J 2021;42:3427-520.
  4. Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013;10:1932-63.
  5. Grimm W, Koehler U, Fus E, et al. Outcome of patients with sleep apnea-associated severe bradyarrhythmias after continuous positive airway pressure therapy. Am J Cardiol 2000;86:688-92.
  6. Brignole M, Auricchio A, Baron-Esquivias G, et al. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the task force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Eur Heart J 2013;34:2281-329.
  7. Steffel J, Robertson M, Singh JP, et al. The effect of QRS duration on cardiac resynchronization therapy in patients with a narrow QRS complex: a subgroup analysis of the EchoCRT trial. Eur Heart J 2015;36:1983-9.
  8. Curtis AB, Worley SJ, Adamson PB, et al. Biventricular pacing for atrioventricular block and systolic dysfunction. N Engl J Med 2013;368:1585-93.
  9. Teigeler T, Kolominsky J, Vo C, et al. Intermediate-term performance and safety of His-bundle pacing leads: a single-center experience. Heart Rhythm 2021;18:743-9.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Pericardial Disease, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and Imaging, Interventions and Vascular Medicine, Computed Tomography, Echocardiography/Ultrasound, Nuclear Imaging, Sleep Apnea

Keywords: ESC Congress, ESC21, Stroke Volume, Bradycardia, Cardiac Resynchronization Therapy, Bundle-Branch Block, Atrioventricular Block, Transcatheter Aortic Valve Replacement, Heart Rate, Exercise Test, Atrial Fibrillation, Heart Failure, Aortic Valve, Bundle of His, Continuous Positive Airway Pressure, Carotid Sinus, Pneumothorax, Pericardial Effusion, Carotid Stenosis, Sex Characteristics, Weight Loss, Electrocardiography, Echocardiography, Syncope, Ventricular Function, Left, Positron-Emission Tomography, Pacemaker, Artificial, Sleep Apnea, Obstructive, Magnetic Resonance Spectroscopy, Morbidity, Hematoma, Genetic Testing, Tomography, Hospitals, Electrophysiology, Reference Standards, Renal Dialysis

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